默克藥廠 (MRK) 2022 Q4 法說會逐字稿

Q4 Sales and Earnings Conference Call. (Operator Instructions) This call is being recorded. If you have any objections, you may disconnect at this time.

第 4 季度銷售和收益電話會議。 （接線員說明）此通話正在錄音中。如果您有異議，此時您可以斷開連接。

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

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

謝謝，早上好。歡迎來到默克 2022 年第四季度電話會議。董事長兼首席執行官 Rob Davis 將在今天的電話會議上發言； Caroline Litchfield，首席財務官；和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 from our non-GAAP results and provide a reconciliation in our press release.

在我們開始之前，我想指出幾點。您會看到我們的 GAAP 結果中有一些項目，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，我們已將這些排除在我們的非 GAAP 結果之外，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's management and are subject to significant risks and uncertainties. If our underlying assumptions prove inaccurate or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

我想提醒您，我們今天發表的一些聲明可能被視為前瞻性聲明，符合 1995 年美國私人證券訴訟改革法案安全港條款的含義。此類聲明是基於當前的信念做出的默克公司的管理層，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出現不確定性，實際結果可能與前瞻性陳述中的結果大不相同。

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，確定了某些風險因素和警示性聲明，這些風險因素和警告性聲明可能導致公司的實際結果與我們今天上午發表的任何前瞻性聲明中預測的結果存在重大差異。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，幻燈片演示將伴隨我們發言人準備好的發言。演示文稿、今天的收益發布以及我們向美國證券交易委員會提交的文件都發佈在默克網站的投資者關係部分。

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

有了這個，我想把電話轉給 Rob。

Thanks, Peter. Good morning, and thank you for joining today's call. 2022 was an exceptional year for Merck. Our science-led strategy is working, and I couldn't be more proud of what our team has delivered scientifically, commercially and operationally. We're focusing on what matters and keeping the patient at the center of everything we do.

謝謝，彼得。早上好，感謝您參加今天的電話會議。 2022 年對默克來說是不平凡的一年。我們以科學為主導的戰略正在奏效，我為我們的團隊在科學、商業和運營方面取得的成就感到無比自豪。我們專注於重要的事情，並將患者置於我們所做一切的中心。

We made significant progress in 2022 advancing our broad pipeline with important internal success complemented by a portfolio of strategic acquisitions, collaborations and partnerships. We've moved with speed and urgency to drive strong progress, and we have provided increased transparency into several of our long-term opportunities, including for GARDASIL, for our cardiovascular pipeline and more recently, from newer assets that leverage our leadership position in oncology. We enter 2023 with even greater confidence that we're creating a sustainable engine that will bring forth innovation and generate value for both patients and shareholders over the long term.

我們在 2022 年取得了重大進展，推進了我們廣泛的產品線，取得了重要的內部成功，並輔之以一系列戰略收購、合作和夥伴關係。我們迅速而緊迫地採取行動以推動強勁的進展，並且我們提高了對幾個長期機會的透明度，包括 GARDASIL、我們的心血管管道以及最近利用我們在腫瘤學領導地位的新資產.進入 2023 年，我們更有信心創造一個可持續發展的引擎，從長遠來看，它將帶來創新並為患者和股東創造價值。

Turning first to our results. The business is performing extremely well. The growth we've experienced in 2022 reflects a sustained track record of fundamental strength from our derisked key growth pillars. We begin the year with confidence that we'll maintain the strong underlying growth after taking into account the significant impact LAGEVRIO had during the height of the pandemic last year and are pleased to reflect this in our 2023 initial guidance.

首先來看我們的結果。業務表現非常出色。我們在 2022 年經歷的增長反映了我們的關鍵增長支柱的基本實力的持續記錄。考慮到 LAGEVRIO 在去年大流行高峰期間產生的重大影響，我們有信心在今年開始時保持強勁的潛在增長，並很高興在我們的 2023 年初步指導中反映這一點。

Importantly, our pipeline is advancing with significant progress across several late-stage programs. In oncology, we have expansive research efforts, including our ambition to move treatment into earlier-stage settings where there is a higher potential for more favorable longer-term outcomes for patients.

重要的是，我們的管道在幾個後期項目中取得了重大進展。在腫瘤學方面，我們開展了廣泛的研究工作，包括我們將治療轉移到早期階段的雄心壯志，在早期階段更有可能為患者帶來更有利的長期結果。

In December, along with our partner, Moderna, we were pleased to announce highly encouraging Phase II results for our personalized mRNA therapeutic cancer vaccine in combination with KEYTRUDA in the treatment of adjuvant melanoma. We're excited by the potential that this combination may have for patients across a range of tumor types. And last week, we were pleased to receive FDA approval for KEYTRUDA for the treatment of certain patients with early-stage non-small cell lung cancer following resection and platinum-based chemotherapy, which Caroline and Dean will speak to.

12 月，我們與我們的合作夥伴 Moderna 一起高興地宣布了我們的個性化 mRNA 治療性癌症疫苗與 KEYTRUDA 聯合治療輔助黑色素瘤的 II 期結果。我們對這種組合對多種腫瘤類型患者的潛力感到興奮。上週，我們很高興獲得 FDA 批准 KEYTRUDA 用於治療某些早期非小細胞肺癌切除術後和含鉑化療後的患者，Caroline 和 Dean 將就此發表講話。

In cardiovascular, we're exploring candidates across a broad range of diseases and have made substantial progress from just 1 year ago. At the American College of Cardiology conference, we will present data from the STELLAR trial evaluating sotatercept in pulmonary arterial hypertension and from the Phase II trial of MK-0616, our oral PCSK9 inhibitor, and we will also host an investor event to discuss these programs.

在心血管方面，我們正在探索廣泛疾病的候選藥物，並且與一年前相比已經取得了實質性進展。在美國心髒病學會會議上，我們將展示評估 sotatercept 治療肺動脈高壓的 STELLAR 試驗和我們的口服 PCSK9 抑製劑 MK-0616 的 II 期試驗數據，我們還將舉辦投資者活動來討論這些項目.

In vaccines, Instituto Butantan in Brazil, with whom we are collaborating for vaccine development, reported very encouraging top line results for their candidate for the prevention of dengue. These data will inform future development of our dengue vaccine, V181, and our efforts to address this critical public health challenge.

在疫苗方面，我們正在與巴西的 Instituto Butantan 合作開發疫苗，報告了他們的候選疫苗在預防登革熱方面非常令人鼓舞的一線結果。這些數據將為我們未來開發登革熱疫苗 V181 以及我們應對這一重大公共衛生挑戰的努力提供信息。

Finally, through our business development efforts, we brought in 4 programs, which will have Phase III trial starts in 2023 and which have the opportunity to contribute meaningful growth during the latter half of this decade and into the next. We are following our disciplined approach to business development and will act when scientific opportunity and value aligned. We have more to do, but I feel very good about the progress we've made in 2022, and we believe that all of these efforts will lead to real benefits for patients and, in turn, for shareholders.

最後，通過我們的業務發展努力，我們引入了 4 個項目，這些項目將於 2023 年開始 III 期試驗，並有機會在本十年後半期和下一個十年中為有意義的增長做出貢獻。我們遵循嚴格的業務發展方法，並將在科學機會和價值一致時採取行動。我們還有更多工作要做，但我對我們在 2022 年取得的進展感到非常滿意，我們相信所有這些努力將為患者帶來真正的利益，進而為股東帶來真正的利益。

We enter 2023 with confidence in the innovation engine we are building and our ability to deliver sustainable value for patients well into the next decade. We will continue to execute on our derisked assets and act with urgency to advance and grow our pipeline. We are doing all of this with an approach to sustainability that is closely aligned to our overall business strategy. I'm very confident in the short and long-term outlook of our company, and I look forward to providing future updates.

進入 2023 年，我們對我們正在打造的創新引擎以及我們在未來十年為患者提供可持續價值的能力充滿信心。我們將繼續執行我們的去風險資產，並緊急行動以推進和發展我們的管道。我們正在採用與我們的整體業務戰略密切相關的可持續發展方法來完成所有這些工作。我對我們公司的短期和長期前景充滿信心，我期待著提供未來的更新。

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 noted, 2022 was an exceptional year for our company. We delivered excellent top line growth of 22%, driven by strength across our key pillars of oncology, vaccines and hospitals as well as the significant contribution from LAGEVRIO.

謝謝你，羅布。早上好。正如 Rob 所說，2022 年對我們公司來說是不平凡的一年。在腫瘤學、疫苗和醫院等關鍵支柱的實力以及 LAGEVRIO 的重大貢獻的推動下，我們實現了 22% 的出色營收增長。

Our Animal Health business delivered strong operational growth, which was offset by foreign exchange. These results are a testament to the profound impact our medicines and vaccines are having on patients globally, which are enabled by our dedicated teams who are executing with excellence to deliver these important innovations. We are confident in the health of our business and in our outlook for continued strong underlying growth.

我們的動物保健業務實現了強勁的運營增長，但被外匯抵消了。這些結果證明了我們的藥物和疫苗對全球患者產生的深遠影響，這是由我們以卓越執行力交付這些重要創新的敬業團隊促成的。我們對我們業務的健康狀況以及持續強勁的潛在增長前景充滿信心。

Now turning to our fourth quarter results. Total company revenues were $13.8 billion, an increase of 2%. Excluding the effects from foreign exchange, the business delivered strong operational growth of 8%. The remainder of my revenue comments will be on an ex-exchange basis. Our Human Health and Animal Health businesses continued their strong growth, increasing 9% and 6%, respectively.

現在轉向我們的第四季度業績。公司總收入為 138 億美元，增長 2%。排除外匯影響，該業務實現了 8% 的強勁運營增長。我對收入的其餘評論將基於匯率換算。我們的人類健康和動物健康業務繼續強勁增長，分別增長 9% 和 6%。

Now turning to the fourth quarter performance of our key brands. In oncology, KEYTRUDA grew 26% to $5.5 billion, driven by strong global demand for in-line indications as well as continued global expansion from new approvals. In the U.S., KEYTRUDA grew across all key tumor types and continued to benefit from uptake in earlier-stage cancers, including triple-negative breast cancer as well as in certain types of renal cell carcinoma and melanoma.

現在轉向我們主要品牌的第四季度業績。在腫瘤領域，KEYTRUDA 增長了 26%，達到 55 億美元，這得益於全球對在線適應症的強勁需求以及新批准的持續全球擴張。在美國，KEYTRUDA 在所有主要腫瘤類型中都有增長，並繼續受益於早期癌症的吸收，包括三陰性乳腺癌以及某些類型的腎細胞癌和黑色素瘤。

KEYTRUDA continues to have a profound impact on patients, including in earlier-stage cancers where there is greater potential for better outcomes. We are excited by the recent approval of KEYNOTE-091, which represents KEYTRUDA's seventh indication in earlier-stage cancers. Early lung cancer detection and screening remain an important unmet need. It is our ambition, along with others, to improve lung center screening rates to levels similar to other tumor types such as breast where screening programs with more routine.

KEYTRUDA 繼續對患者產生深遠影響，包括早期癌症，這些患者有更大的潛力獲得更好的結果。我們對最近批准的 KEYNOTE-091感到興奮，它代表了 KEYTRUDA 在早期癌症中的第七個適應症。早期肺癌檢測和篩查仍然是一項重要的未滿足需求。我們的目標是與其他人一起，將肺中心篩查率提高到與其他腫瘤類型（例如乳腺癌）相似的水平，其中篩查計劃更為常規。

While we are committed to addressing this unmet need, we anticipate a more gradual near-term uptake from this indication. In the metastatic setting, KEYTRUDA maintains its leadership position in non-small cell lung cancer, which gives us confidence that we are well positioned to positively impact patients in the earlier setting.

雖然我們致力於解決這一未滿足的需求，但我們預計近期會從這一跡像中獲得更漸進的吸收。在轉移性環境中， KEYTRUDA 保持其在非小細胞肺癌領域的領導地位，這讓我們相信，我們有能力在早期環境中對患者產生積極影響。

Outside the U.S., KEYTRUDA growth continues to be driven by uptake in metastatic indications, including non-small cell lung cancer, head and neck cancer and renal cell carcinoma as well as recent launches in earlier-stage cancers, including 30 types of high-risk, early-stage triple negative breast cancer and renal cell carcinoma.

在美國以外，KEYTRUDA 的增長繼續受到轉移適應症的採用，包括非小細胞肺癌、頭頸癌和腎細胞癌，以及最近在早期癌症中的推出，包括 30 種高危癌症，早期三陰性乳腺癌和腎細胞癌。

Lynparza maintained its leadership of the PARP inhibitor class. Alliance revenue grew 14%, primarily due to continued demand in certain patients with high-risk, early-stage breast cancer. Lenvima alliance revenue grew 9%, driven by increased uptake in the treatment of certain patients with advanced renal cell carcinoma and advanced endometrial cancer in the U.S.

Lynparza 保持其在 PARP 抑製劑類別中的領導地位。聯盟收入增長了 14%，這主要是由於某些高風險、早期乳腺癌患者的持續需求。 Lenvima 聯盟的收入增長了 9%，這是由於美國某些晚期腎細胞癌和晚期子宮內膜癌患者的治療接受度增加所致

Lastly, WELIREG is performing in line with our expectations, and we are proud of the impact this is having on adult patients with certain VHL-associated tumors. Our vaccines portfolio delivered growth, with GARDASIL increasing 6% to $1.5 billion, driven by strong demand in major ex-U.S. markets, particularly China. In the U.S., sales decreased primarily due to CDC purchasing patterns. Vaccine sales also benefited from the pediatric launch of VAXNEUVANCE, which is off to an encouraging start, with revenues also benefiting from inventory stocking.

最後，WELIREG 的表現符合我們的預期，我們為它對患有某些 VHL 相關腫瘤的成年患者產生的影響感到自豪。我們的疫苗產品組合實現增長，其中 GARDASIL 增長 6% 至 15 億美元，這主要得益於美國以外主要地區的強勁需求。市場，尤其是中國。在美國，銷售額下降主要是由於 CDC 的採購模式。疫苗銷售也受益於 VAXNEUVANCE 的兒科上市，這是一個令人鼓舞的開端，收入也受益於庫存庫存。

In our hospital acute care portfolio, BRIDION sales grew 7%, driven by an increase in market share amongst neuromuscular blockade reversal agents and an increase in surgical procedures. Hospital acute care sales also benefited from the resupply of the ZERBAXA, which started in the fourth quarter of 2021.

在我們的醫院急症護理產品組合中，受神經肌肉阻斷逆轉劑市場份額增加和外科手術增加的推動，BRIDION 銷售額增長了 7%。醫院急症護理銷售也受益於 ZERBAXA 的補給，該補給於 2021 年第四季度開始。

Our Animal Health business delivered another solid quarter, with sales increasing 6%, reflecting strategic price actions and volume growth. Livestock sales grew 12%, driven by increased demand in ruminants and poultry products. Companion animal sales were negatively impacted by supply challenges for certain vaccines and a reduction in vet visits in October, which improved during the quarter.

我們的動物保健業務實現了又一個穩定的季度，銷售額增長 6%，反映出戰略價格行動和銷量增長。受反芻動物和家禽產品需求增加的推動，牲畜銷售額增長了 12%。伴侶動物的銷售受到某些疫苗供應挑戰和 10 月份獸醫就診次數減少的負面影響，該情況在本季度有所改善。

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 75.7%, an increase of 0.9 percentage points due to favorable product mix and foreign exchange. Operating expenses increased 8% to $5.7 billion, reflecting increased investments to support our portfolio and growing pipeline. Other income was $86 million, reflecting the return on pension plan assets and capitalized interest, which was largely offset by net interest expense. Our tax rate was 15.6%. Taken together, earnings per share were $1.62.

我現在將向您介紹我們剩餘的損益表，我的評論將基於非公認會計原則。毛利率為 75.7%，增長 0.9 個百分點，得益於有利的產品組合和匯率。營業費用增加 8% 至 57 億美元，反映出增加投資以支持我們的投資組合和不斷增長的管道。其他收入為 8600 萬美元，反映了養老金計劃資產和資本化利息的回報，這在很大程度上被淨利息支出所抵消。我們的稅率是 15.6%。兩者合計，每股收益為 1.62 美元。

Turning now to our 2023 non-GAAP guidance. The strength across our key pillars is expected to continue into this year. We project revenue to be between $57.2 billion and $58.7 billion, including approximately $1 billion from LAGEVRIO. Excluding the negative impact of LAGEVRIO and an approximate 2% negative impact from foreign exchange using mid-January rates, we expect strong underlying revenue growth 7% to 10%. Our gross margin is expected to be approximately 77%.

現在轉向我們的 2023 年非公認會計原則指南。我們主要支柱的實力預計將持續到今年。我們預計收入在 572 億美元至 587 億美元之間，其中包括來自 LAGEVRIO 的約 10 億美元。排除 LAGEVRIO 的負面影響和使用 1 月中旬匯率計算的外匯帶來的約 2% 的負面影響，我們預計基礎收入將強勁增長 7% 至 10%。我們的毛利率預計約為 77%。

Operating expenses are assumed to be between $23.1 billion and $24.1 billion, which includes $1.4 billion of research and development expenses related to our acquisition of Imago and the expansion of our collaboration with Kelun-Biotech. As a reminder, our guidance does not assume additional significant potential business development transactions.

假設運營費用在 231 億美元至 241 億美元之間，其中包括 14 億美元與我們收購 Imago 和擴大與 Kelun-Biotech 的合作相關的研發費用。提醒一下，我們的指南不假設額外的重大潛在業務發展交易。

Other income is anticipated to be approximately $250 million. We assume a full year tax rate between 17% and 18% and approximately 2.55 billion shares outstanding. Taken together, we expect EPS of $6.80 to $6.95. This range includes a negative impact from foreign exchange of approximately 4% using mid-January rates.

其他收入預計約為 2.5 億美元。我們假設全年稅率在 17% 至 18% 之間，流通股約為 25.5 億股。綜上所述，我們預計每股收益為 6.80 美元至 6.95 美元。該範圍包括使用 1 月中旬匯率計算的大約 4% 的外匯負面影響。

Our guidance reflects confidence in continued strong growth across oncology, vaccines and Animal Health. As you consider your models, there are a few items to keep in mind. On revenues, we are confident in our ability to drive strong growth of GARDASIL, particularly in international markets. Global immunization levels remain low, which creates a tremendous opportunity to benefit more patients. And we are improving supply, which positions us well to support the significant demand we are experiencing today and expect over the long term for this vaccine that prevents HPV-related cancers.

我們的指引反映了對腫瘤學、疫苗和動物保健領域持續強勁增長的信心。當您考慮您的模型時，需要記住一些事項。在收入方面，我們有信心推動 GARDASIL 的強勁增長，尤其是在國際市場。全球免疫水平仍然很低，這為造福更多患者創造了巨大機會。我們正在改善供應，這使我們能夠很好地支持我們今天遇到的巨大需求，並期待這種疫苗能夠預防 HPV 相關癌症的長期需求。

Other revenue is projected to decline significantly, primarily reflecting a smaller planned benefit from revenue hedges following the U.S. dollar strength last year, which resulted in an approximate $800 million benefit in 2022. Other revenue is also expected to be lower due to the discontinuation of third-party manufacturing sales to Johnson and Johnson.

其他收入預計將大幅下降，主要反映了去年美元走強後收入對沖的計劃收益減少，這導致 2022 年收益約為 8 億美元。其他收入預計也將下降，因為第三個- 對強生公司的派對製造銷售。

On the rest of the P&L, we project the shift from other expense to other income, which is primarily attributable to an assumption that there will be no pension settlement costs as well as an expectation of lower net interest expense and higher joint venture equity income. This benefit is more than offset by an increase in the estimated tax rate due to the unfavorable impact of the R&D capitalization provision as well as an approximate 1 percentage point impact related to Imago.

在損益表的其餘部分，我們預計將從其他費用轉移到其他收入，這主要是由於假設沒有養老金結算成本以及淨利息費用較低和合資企業股權收入較高的預期。由於研發資本化規定的不利影響以及與 Imago 相關的大約 1 個百分點的影響，估計稅率的增加抵消了這一收益。

Now shifting 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 excited about the significant progress our teams have made to advance and augment our pipeline in 2022.

現在轉向資本配置，我們的優先事項保持不變。我們將繼續優先投資於我們的業務，以推動近期和長期增長。我們對我們的團隊在 2022 年推進和擴充我們的管道方面取得的重大進展感到興奮。

In 2023, we will continue to invest in opportunities that will address important unmet medical needs and drive the next wave of growth for our company, including the initiation of many late-stage clinical trials across a broad set of novel candidates. We remain committed to our dividend with the goal of increasing it over time.

2023 年，我們將繼續投資於解決重要未滿足醫療需求並推動公司下一波增長的機會，包括在廣泛的新候選藥物中啟動許多後期臨床試驗。我們仍然致力於我們的股息，目標是隨著時間的推移增加它。

We will continue to pursue the most compelling external science through value-enhancing business development to augment our internal pipeline, and we'll invest appropriately maximize the potential of our program. Given the strength of our business and balance sheet, we plan to resume share repurchases, while ensuring we maintain ample capacity to pursue additional business development, which is the higher priority.

我們將繼續通過提升價值的業務發展來追求最引人注目的外部科學，以擴大我們的內部管道，我們將適當投資以最大限度地發揮我們項目的潛力。鑑於我們的業務和資產負債表的實力，我們計劃恢復股票回購，同時確保我們保持足夠的能力來追求更多的業務發展，這是更高的優先級。

To conclude, we entered 2023 confident in our ability to execute on the important opportunities we have to deliver innovation to patients and sustain the strong underlying growth of our business well into the future.

總而言之，進入 2023 年，我們有信心抓住重要機會，為患者提供創新，並在未來保持我們業務的強勁潛在增長。

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迪恩。

Thank you, Caroline. Today, I will provide notable updates since our last earnings call. We continue to make significant advancements and achieve important regulatory milestones. The fourth quarter marks the end of a successful year with progress made across oncology, vaccines, infectious diseases and cardiology.

謝謝你，卡羅琳。今天，我將提供自上次財報電話會議以來的重要更新。我們繼續取得重大進展並實現重要的監管里程碑。第四季度標誌著在腫瘤學、疫苗、傳染病和心髒病學方面取得進展的成功一年的結束。

Let me start with oncology. We remain committed to transforming the landscape of cancer therapy with an ongoing focus on treating earlier stages of disease. We are pleased by the recent approval of KEYTRUDA for the adjuvant treatment of adult patients with stage Ib, II or IIIa non-small cell lung cancer following resection and platinum-based chemotherapy based on the results of KEYNOTE-091. This approval provides, for the very first time, an adjuvant immunotherapy option for this patient population with stage 1b disease and regardless of PD-L1 status.

讓我從腫瘤學開始。我們仍然致力於改變癌症治療的格局，持續關注治療早期疾病。我們很高興最近根據 KEYNOTE-091 的結果批准 KEYTRUDA 用於 Ib 、 II 或 IIIa 期非小細胞肺癌成人患者的輔助治療。該批准首次為患有 1b 期疾病且無論 PD-L1 狀態如何的患者群體提供了輔助免疫治療選擇。

Beyond KEYNOTE-091, we have additional ongoing studies in earlier stages of non-small cell lung cancer, including: KEYNOTE-671 evaluating KEYTRUDA with platinum doublet chemotherapy as neoadjuvant followed by adjuvant therapy in resectable stage II, IIIa and IIIb disease; KEYNOTE-867 evaluating KEYTRUDA in patients undergoing stereotactic body radiotherapy with unresected stage I or II disease; and KEYLYNK-012 studying KEYTRUDA in combination with Lynparza in Stage III disease.

除了 KEYNOTE-091 之外，我們還在非小細胞肺癌的早期階段進行其他正在進行的研究，包括： KEYNOTE-671 評估 KEYTRUDA 聯合鉑類雙藥化療作為新輔助治療，隨後輔助治療可切除的 II、IIIa 和 IIIb 期疾病； KEYNOTE-867 評估 KEYTRUDA 在接受立體定向放療且未切除的 I 期或 II 期疾病患者中的療效；和 KEYLYNK-012 研究 KEYTRUDA 與 Lynparza 聯合治療 III 期疾病。

These trials are all part of our broader effort to treat earlier stages of cancer and further improve patient outcomes across, tumor types, such as melanoma. Together with Moderna, we announced positive Phase II results for V940, mRNA-4157 in combination with KEYTRUDA for the adjuvant treatment of stage III and IV for melanoma in patients with high risk of recurrence following complete resection. The combination demonstrated a statistically significant and clinically meaningful improvement in recurrence free survival versus KEYTRUDA alone.

這些試驗都是我們更廣泛努力的一部分，旨在治療早期癌症並進一步改善各種腫瘤類型（例如黑色素瘤）的患者預後。我們與 Moderna 一起宣布了 V940、mRNA-4157 與 KEYTRUDA 聯合用於輔助治療完全切除後復發風險高的黑色素瘤 III 期和 IV 期黑色素瘤的 II 期陽性結果。與單獨使用 KEYTRUDA 相比，該組合在無復發生存率方面表現出統計學意義和臨床意義的改善。

This investigational personalized neoantigen therapy utilizes mRNA technology and is specifically tailored to target the unique mutational signature of each patient's tumor. We plan to discuss the results with regulators and initiate Phase III trials in multiple tumors this year. Detailed results will be presented at an upcoming medical meeting.

這種研究性個性化新抗原療法利用 mRNA 技術，專門針對每位患者腫瘤的獨特突變特徵量身定制。我們計劃與監管機構討論結果，並在今年啟動多種腫瘤的 III 期試驗。詳細結果將在即將召開的醫學會議上公佈。

We also announced positive results from the Phase III KEYNOTE-966 trial evaluating KEYTRUDA in combination with chemotherapy. This trial demonstrated an improvement in overall survival for the first-line treatment of patients with advanced or unresectable biliary tract cancer.

我們還公佈了評估 KEYTRUDA 聯合化療的 III 期 KEYNOTE-966試驗的積極結果。該試驗表明，對晚期或無法切除的膽道癌患者進行一線治療可提高總生存期。

In addition, we announced positive top line results from the Phase III KEYNOTE-859 trial evaluating KEYTRUDA in combination with chemotherapy for the first-line treatment of patients with HER2-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.

此外，我們還公佈了 III 期 KEYNOTE-859試驗的陽性頂線結果，該試驗評估 KEYTRUDA 聯合化療一線治療 HER2陰性局部晚期不可切除或轉移性胃癌或胃食管交界處腺癌患者。

In November, we announced the acquisition of Imago BioSciences, which closed last month. Imago's lead candidate, bomedemstat, is a potentially first-in-class orally available lysine-specific demethylase 1 inhibitor. It is currently being evaluated in multiple Phase II clinical trials for the treatment of essential thrombocythemia, myelofibrosis and polycythemia vera.

11 月，我們宣布收購上個月完成的 Imago BioSciences。 Imago 的主要候選藥物 bomedemstat 是一種潛在的一流口服賴氨酸特異性脫甲基酶 1 抑製劑。目前正在多項 II 期臨床試驗中評估它用於治療原發性血小板增多症、骨髓纖維化和真性紅細胞增多症。

The combined team is now focused on continuing to advance the ongoing clinical development programs. At the American Society of Hematology annual meeting, data were presented from multiple pipeline candidates, including: favezelimab, our anti-LAG3 antibody; zilovertamab vedotin, an antibody drug conjugate, targeting ROR-1; and nemtabrutinib, our oral reversible, non-covalent BTK inhibitor; as well as KEYTRUDA. Updated Phase II data for bomedemstat in essential thrombocythemia and advanced myelofibrosis were also presented.

合併後的團隊現在專注於繼續推進正在進行的臨床開發計劃。在美國血液學會年會上，展示了來自多個管道候選人的數據，包括：favezelimab，我們的抗 LAG3 抗體； zilovertamab vedotin，一種靶向 ROR-1 的抗體藥物偶聯物；和 nemtabrutinib，我們的口服可逆非共價 BTK 抑製劑；以及 KEYTRUDA。還提供了博美司他治療原發性血小板增多症和晚期骨髓纖維化的最新 II 期數據。

We continue to deliver on our regulatory strategy. In the European Union, along with our partner, AstraZeneca, we announced the approval for Lynparza in combination with abiraterone and prednisone for the treatment of certain patients with metastatic castration-resistant prostate cancer based on the results of the PROpel trial. In China, based on the results of KEYNOTE-522 and KEYNOTE 394 in we received approvals for KEYTRUDA in neoadjuvant/adjuvant high-risk, early-stage triple-negative breast cancer and hepatocellular carcinoma, respectively.

我們繼續實施我們的監管戰略。在歐盟，我們與我們的合作夥伴阿斯利康一起，根據 PROpel 試驗的結果，宣布批准 Lynparza 與阿比特龍和潑尼松聯合用於治療某些轉移性去勢抵抗性前列腺癌患者。在中國，根據 KEYNOTE-522 和 KEYNOTE 394 的結果，我們分別獲得了 KEYTRUDA 用於新輔助/輔助高風險、早期三陰性乳腺癌和肝細胞癌的批准。

With our partners, Astellas and Seagen, we announced the FDA has accepted supplemental biologic license application for KEYTRUDA with PADCEV, an antibody drug conjugate targeting Nectin-4, for the first-line treatment of certain patients with locally advanced or metastatic urothelial cancer who are not eligible to receive cisplatin-containing chemotherapy. The agency set a PDUFA date of April 21, 2023, for each application.

我們與我們的合作夥伴 Astellas 和 Seagen 一起宣布，FDA 已接受 KEYTRUDA 與 PADCEV 的補充生物許可申請，PADCEV 是一種靶向 Nectin-4 的抗體藥物偶聯物，用於一線治療某些患有局部晚期或轉移性尿路上皮癌的患者，這些患者是沒有資格接受含順鉑的化療。該機構為每份申請設定了 PDUFA 日期為 2023 年 4 月 21 日。

Building on the clinical benefits observed with KEYTRUDA in combination with chemotherapy and antibody drug conjugates, we have focused on augmenting our tissue targeting candidates through business development. We announced the expansion of our agreement with Kelun-Biotech with the addition of up to 7 preclinical antibody drug conjugates.

基於 KEYTRUDA 結合化療和抗體藥物偶聯物觀察到的臨床益處，我們專注於通過業務發展來增強我們的組織靶向候選藥物。我們宣布擴大與科倫生物的協議，增加多達 7 種臨床前抗體藥物偶聯物。

The collaboration leverages technology with the potential to yield a new generation of candidates designed to precisely target and deliver potent anticancer agents to the tumor site. This follows previously disclosed agreement for 2 clinical stage candidates, including MK-2870, an investigational TROP2 targeting ADC we are planning to advance into Phase III trials this year. We also expanded our collaboration with PeptiDream to include the discovery and development of peptide drug conjugates. This technology potentially provides for improved permeability and drug selectivity in targeting tumor tissue.

該合作利用了有可能產生新一代候選藥物的技術，這些候選藥物旨在精確定位並向腫瘤部位輸送有效的抗癌藥物。此前已就 2 個臨床階段候選藥物（包括 MK-2870）達成協議，我們計劃在今年推進 III 期試驗。我們還擴大了與 PeptiDream 的合作，包括發現和開發肽藥物偶聯物。該技術可能會提高靶向腫瘤組織的滲透性和藥物選擇性。

Next to our vaccine portfolio. We were encouraged by the progress scientists and clinicians at the Instituto Butantan in Brazil made in developing a single dose dengue vaccine candidate for registration in Brazil. We are collaborating with the team there to conduct a detailed analysis of these positive topline Phase III results to determine next steps for our own dengue vaccine candidate, V181, currently in Phase II development. Merck’s goal is to make V181 available outside of Brazil for populations at risk for dengue.

在我們的疫苗組合旁邊。巴西 Instituto Butantan 的科學家和臨床醫生在開髮用於在巴西註冊的單劑量登革熱候選疫苗方面取得的進展令我們感到鼓舞。我們正在與那裡的團隊合作，對這些積極的 III 期頂線結果進行詳細分析，以確定我們自己的登革熱候選疫苗 V181 的後續步驟，該疫苗目前處於 II 期開發階段。默克的目標是讓巴西以外的登革熱高危人群能夠獲得 V181。

As Caroline noted, we are receiving positive feedback from the field regarding the recent launch of VAXNEUVANCE in the pediatric setting, and remain confident in our population specific strategy for the prevention of pneumococcal disease.

正如 Caroline 指出的那樣，我們正在收到來自該領域的關於最近在兒科環境中推出 VAXNEUVANCE 的積極反饋，並對我們預防肺炎球菌疾病的特定人群策略充滿信心。

VAXNEUVANCE offers strong protection, including in the first year of life, with robust immunity across all shared and unique serotypes. This is important because the incidence of invasive pneumococcal disease is greatest in the first year of life for children. Also, we are on track and look forward to the Phase III results from our V116 program for the protection of adults this year.

VAXNEUVANCE 提供強大的保護，包括在生命的第一年，對所有共享和獨特的血清型具有強大的免疫力。這很重要，因為侵襲性肺炎球菌疾病的發病率在兒童出生後的第一年最高。此外，我們正在步入正軌，並期待著今年保護成年人的 V116 計劃的 III 期結果。

We, along with others in the industry, are making a real impact in our goal to help reduce cancer incidence. It was noteworthy that the American Cancer Society’s recently published annual report on cancer facts and trends included the remarkable observation that there has been a 65 percent reduction in cervical cancer incidence in women 20 to 24 years old, from 2012 through 2019.

我們與業內其他人一起，正在對我們幫助降低癌症發病率的目標產生真正的影響。值得注意的是，美國癌症協會最近發布的關於癌症事實和趨勢的年度報告包括一項引人注目的觀察結果，即從 2012 年到 2019 年，20 至 24 歲女性的宮頸癌發病率降低了 65%。

It is this type of finding that further reinforces Merck’s commitment to bringing forward treatment and prevention options to help patients with this devastating disease. As part of this commitment, we are encouraged by the role GARDASIL continues to play in helping to prevent certain HPV-related cervical cancers.

正是這種類型的發現進一步加強了默克公司提出治療和預防方案以幫助患有這種毀滅性疾病的患者的承諾。作為這一承諾的一部分，我們對 GARDASIL 在幫助預防某些 HPV 相關宮頸癌方面繼續發揮的作用感到鼓舞。

Turning to the broader portfolio. With the continued impact of COVID-19 in China, treatment options are urgently needed to help reduce the incidence of disease and burden on healthcare systems. We were pleased LAGEVRIO was granted conditional marketing authorization by China's National Medical Products Administration in December, for use in adult patients who have mild to moderate COVID-19 infection and a high risk of progressing to severe cases.

轉向更廣泛的投資組合。隨著 COVID-19 在中國的持續影響，迫切需要治療方案來幫助降低疾病的發病率和醫療系統的負擔。我們很高興 LAGEVRIO 於去年 12 月獲得中國國家藥品監督管理局有條件的上市許可，用於輕度至中度 COVID-19感染和進展為重症病例的高風險的成年患者。

I wish to reinforce something Rob mentioned. Please mark your calendars for March 6, where we will present detailed findings of the Phase III STELLAR trial, evaluating sotatercept in patients with pulmonary arterial hypertension and the Phase II results for MK-0616, our oral PCSK9 inhibitor, at the American College of Cardiology in conjunction with the World Congress of Cardiology meeting in New Orleans.

我想強調 Rob 提到的一些事情。請將您的日曆標記為 3 月 6 日，屆時我們將在美國心髒病學會公佈 III 期 STELLAR 試驗的詳細結果，評估肺動脈高壓患者的 sotatercept 以及我們的口服 PCSK9 抑製劑 MK-0616 的 II 期結果與在新奧爾良舉行的世界心髒病學大會一起舉行。

We will also host a live investor event to answer your questions. We look forward to bringing sotatercept as an important treatment option to patients and are currently working towards submission of the data from the STELLAR trial. We are in discussions with the FDA about submission of the data on a rolling basis, which is likely to result in a potential approval in early 2024.

我們還將舉辦現場投資者活動來回答您的問題。我們期待將 sotatercept 作為患者的重要治療選擇，目前正在努力提交 STELLAR 試驗的數據。我們正在與 FDA 討論滾動提交數據的問題，這很可能會在 2024 年初獲得批准。

As we close out 2022, it is important to highlight that over the course of the year we made strong progress across therapeutic areas, modalities, stages of development and multiple business development transactions.

在我們結束 2022 年之際，重要的是要強調，在這一年中，我們在治療領域、模式、發展階段和多項業務發展交易方面取得了長足進步。

In oncology, we obtained several important regulatory approvals globally for KEYTRUDA, and Lynparza as well as advanced a number of programs evaluating earlier stage cancer regimens. In vaccines, we received an important approval in pediatrics for VAXNEUVANCE. In addition, we were granted expanded authorizations in China, and active recommendations were reinstated in Japan for GARDASIL. In HIV, we resumed our clinical development program for islatravir. And finally in cardiovascular disease, we made significant progress across our pulmonary arterial hypertension and hypercholesterolemia programs.

在腫瘤學方面，我們在全球範圍內為 KEYTRUDA 和 Lynparza 獲得了幾項重要的監管批准，並推進了許多評估早期癌症治療方案的項目。在疫苗方面，我們在兒科領域獲得了 VAXNEUVANCE 的重要批准。此外，我們在中國獲得了擴大的授權，並在日本恢復了 GARDASIL 的積極推薦。在 HIV 方面，我們恢復了 islatravir 的臨床開發計劃。最後，在心血管疾病方面，我們在肺動脈高壓和高膽固醇血症項目中取得了重大進展。

Taken together, we continue to deliver on our strategy of advancing promising candidates across multiple therapeutic areas. We have strong momentum across our pipeline and look forward to providing further updates on our progress in 2023.

綜上所述，我們繼續實施我們的戰略，在多個治療領域推進有前途的候選人。我們在整個管道中都有強勁的勢頭，並期待在 2023 年提供有關我們進展的進一步更新。

And now I will turn the call back to Peter.

現在我會把電話轉回給彼得。

Thanks, Dean. Kelly, we're ready to take questions now. We intend to end the call at 9:00 sharp this morning. (Operator Instructions)

謝謝，院長。凱利，我們現在準備好提問了。我們打算在今天早上 9:00 整結束通話。 （操作員說明）

(Operator Instructions) Our first question is from Carter Gould from Barclays.

（操作員說明）我們的第一個問題來自巴克萊銀行的卡特古爾德。

Maybe just you made some comments around sort of uptake in the adjuvant setting after the most recent label update. Can you maybe just sort of set expectations there? And does that comment reflect any sort of assumptions around when we might see mature data from the PEARLE study potentially this year?

也許只是你在最近的標籤更新後就佐劑設置中的某種攝取發表了一些評論。你能不能在那裡設定一些期望？該評論是否反映了我們可能在今年看到 PEARLE 研究的成熟數據的任何類型的假設？

Yes. So I believe you're speaking about KEYNOTE-091. So I just want to take a broad view and then the today view and the tomorrow view. So I would just count that the American Cancer Society in 2023, it's really remarkable. They suggest that for between 1991 and 2023, there's a massive reduction in lung cancer of 58%, 36%, and KEYTRUDA has been critical in that story.

是的。所以我相信你在談論 KEYNOTE-091。所以我只想看一個廣泛的觀點，然後是今天的觀點和明天的觀點。所以我只算 2023 年的美國癌症協會，這真的很了不起。他們認為，在 1991 年至 2023 年期間，肺癌的發病率大幅減少了 58%、36%，而 KEYTRUDA 在這個故事中發揮了關鍵作用。

And now we're moving to early lung. The label is broad. It is regardless of PD-L1, and it reflects the clinical trial, where we demonstrated a 27% reduction. We're pushing into these earlier lines with other trials. But I think for -- what we need to set for is 2 things. We need to make it much more easier, with scientific innovation, other means to get subcu -- to get KEYTRUDA. And that's why we're very eager to push our subcu pembrolizumab with (inaudible) into Phase III this year. But we also need to do a lot to improve adherence to established guidelines, which currently only have 6% or so of individuals actually who should be screened, being screened in the United States.

現在我們正在轉向早期肺。標籤範圍很廣。它與 PD-L1 無關，它反映了臨床試驗，我們在臨床試驗中證明了 27% 的減少。我們正在通過其他試驗推進這些較早的生產線。但我認為 - 我們需要設定的是兩件事。我們需要讓它變得更容易，通過科學創新，其他方法來獲得 subcu——獲得 KEYTRUDA。這就是為什麼我們非常渴望在今年將我們的 subcu pembrolizumab（聽不清）推入 III 期。但我們還需要做很多工作來提高對既定指南的遵守程度，目前在美國祇有 6% 左右的人實際上應該接受篩查。

So I think with that, we have work to do in relationship to really taking this important advance and making it broadly available through to individuals who should be getting screened, screened.

因此，我認為，我們有很多工作要做，以真正取得這一重要進展，並將其廣泛提供給應該接受篩查、篩查的個人。

So Carter, maybe I can just add on a little bit about the commercial opportunity. As Dean said, this will be a slower ramp because we have to drive more people to get diagnosed early so that we can get them the care they need.

所以卡特，也許我可以補充一點商業機會。正如 Dean 所說，這將是一個緩慢的增長，因為我們必須促使更多的人及早得到診斷，這樣我們才能為他們提供所需的護理。

But just to give you some sizing of this. If you look at 2023, there are about 230,000 people who were diagnosed with lung cancer in U.S. And the majority of that group was not diagnosed until they were in the metastatic setting. So if you think about it from a minority perspective, we would estimate about 120,000 people in the early-stage setting, of which only 1/4 will have a section -- or have surgery and be in the stage Ib through IIIa, which is what our label indicates.

但只是為了給你一些尺寸。如果你看看 2023 年，美國大約有 230,000 人被診斷出患有肺癌，而這群人中的大多數直到他們處於轉移環境中才被診斷出來。因此，如果你從少數人的角度考慮，我們估計大約有 120,000 人處於早期階段，其中只有 1/4 會進行切片——或進行手術並處於 Ib 到 IIIa 階段，即我們的標籤表示什麼。

So you're looking at about 30,000 patients who would be the addressable population. And then obviously, of that group, historically, only about half of those patients have gone on to receive treatment in the form of chemotherapy or IO. So that's obviously something we hope to change as we go forward because we think the outcome will show that if you are resected, you should pursue KEYTRUDA in that setting. And it's our goal over time not only to drive more patients in that segment, but obviously, the more people we can get diagnosed early pre-metastatic, then actually we will expand the population over time.

所以你正在尋找大約 30,000 名患者，他們將是可尋址的人群。然後很明顯，從歷史上看，在這組患者中，只有大約一半的患者繼續接受化療或 IO 形式的治療。所以這顯然是我們希望在前進過程中改變的事情，因為我們認為結果將表明，如果你被切除，你應該在那種情況下追求 KEYTRUDA。隨著時間的推移，我們的目標不僅是在該領域吸引更多患者，而且顯然，我們可以在早期轉移前診斷出越多的人，那麼實際上我們將隨著時間的推移擴大人口。

So we see this as a meaningful opportunity long term, but it's going to take us time to ramp as we work to change the paradigm that's existed in the past.

因此，從長遠來看，我們認為這是一個有意義的機會，但在我們努力改變過去存在的範式時，我們需要時間來加速發展。

Thank you, Carter. Next question, please, Kelly.

謝謝你，卡特。下一個問題，請凱利。

Our next question is going to come from Andrew Baum from Citi.

我們的下一個問題將來自花旗銀行的 Andrew Baum。

A couple of questions. Could you please address the demand on Merck's business to plug the hole associated with the KEYTRUDA LOE post-2028? Alternatively, instead, just build the exit growth rate and focus less on finding revenues to plug the hole as you think about your BD strategy.

幾個問題。您能否解決對默克公司業務的需求，以填補與 2028 年後的 KEYTRUDA LOE 相關的漏洞？或者，在考慮 BD 戰略時，只需建立退出增長率，而不是專注於尋找收入來填補漏洞。

And perhaps quickly for Dean, could you just give us some guidance on the timing for the PFS analysis and the PD-L1 high, greater-than-50 cohort from KEYVIBE-003. Should we expect it in the next 12 months? I know the total PFS read for the whole trial is somewhere in '24, but it strikes me you may have a separate analysis for that greater-than-50 subgroup.

也許 Dean 很快，您能否就 PFS 分析的時間和來自 KEYVIBE-003 的 PD-L1 高、大於 50 隊列給我們一些指導。我們應該在未來 12 個月內期待它嗎？我知道整個試驗的總 PFS 讀數在 24 年左右，但令我印象深刻的是，您可能對大於 50 的子組進行了單獨分析。

Great. Well, maybe, Andrew, I'll start off, and if Caroline or Dean want to jump in. But to give you a sense -- and obviously, we haven't given specific guidance to the LOE period. But just to ground everyone in the facts, KEYTRUDA and our expectation will lose exclusivity in the United States in 2028 and in China in 2028. It loses it in Europe in 2030 and in Japan in 2032.

偉大的。嗯，也許，安德魯，我會開始，如果 Caroline 或 Dean 想加入。但是為了給你一個感覺——很明顯，我們沒有給出 LOE 時期的具體指導。但為了讓每個人都了解事實，KEYTRUDA 和我們的預期將在 2028 年在美國和 2028 年在中國失去排他性。它在 2030 年在歐洲和 2032 年在日本失去它。

So obviously, by shorthand, we refer to '28, but the reality of it is over most of the markets, and KEYTRUDA increasingly is becoming obvious, as you know, a global product. It's spread out. But as we look at where we sit today, I would say we feel good about the progress we've made. We're confident that we're on a path to sustainable growth into the next decade. Obviously, we have more work to do, but I would just point you to a few proof points that I think support that.

因此，很明顯，通過速記，我們指的是'28，但它的現實已經遍及大多數市場，而 KEYTRUDA 越來越明顯，正如你所知，它是一種全球產品。它散開了。但當我們審視今天的情況時，我想說我們對所取得的進展感到滿意。我們相信，我們正走在通往下一個十年可持續增長的道路上。顯然，我們還有更多工作要做，但我只想向您指出幾個我認為支持這一點的證據。

First of all, as we talked about in the last 18 months, we've made meaningful progress in our cardiovascular pipeline, we have 8 potential approvals between 2025 and 2030, obviously. The centerpiece of that is sotatercept and what we're seeing from the STELLAR data, which really was just quite phenomenal. If you look at that, we expect those products, that portfolio of opportunity on an unrisk-adjusted basis to be in excess of $10 billion as you approach the mid-2030s.

首先，正如我們在過去 18 個月中談到的那樣，我們在心血管管道方面取得了有意義的進展，很明顯，我們在 2025 年至 2030 年之間有 8 項潛在批准。其中的核心是 sotatercept 以及我們從 STELLAR 數據中看到的，這確實非常驚人。如果你看一下，我們預計這些產品，當你接近 2030 年代中期時，在未風險調整的基礎上的機會組合將超過 100 億美元。

We recently discussed the fact that through the business development deals we've done, we've brought in new assets apart from KEYTRUDA, apart from Lynparza, Lenvima and WELIREG, that themselves, these new mechanisms, I would point you to things like ORION and Imago. Those products, along with what we see in the ADC space, as a portfolio, we think themselves have the potential for $10 billion or more of revenue as you get into the early to mid-2030s.

我們最近討論了這樣一個事實，即通過我們已經完成的業務開發交易，除了 KEYTRUDA，除了 Lynparza、Lenvima 和 WELIREG，我們還引入了新資產，這些新機製本身，我會向你指出 ORION 之類的東西和意象。這些產品，連同我們在 ADC 領域看到的產品，作為一個產品組合，我們認為當您進入 2030 年代初期至中期時，它們本身俱有 100 億美元或更多收入的潛力。

So today, we sit there with the expectation that we are starting to make meaningful progress, and that excludes all the work we're doing to bring an incremental value to patients on KEYTRUDA. Obviously, as great as KEYTRUDA is, it still only has an overall response rate averaging around 30%.

所以今天，我們坐在那裡期望我們開始取得有意義的進展，這不包括我們為 KEYTRUDA 患者帶來增量價值所做的所有工作。顯然，儘管 KEYTRUDA 非常出色，但它的總體響應率仍然只有平均 30% 左右。

We need to deepen and drive better response. We're looking to do that through combinations and through other means to find ways to improve on KEYTRUDA. We're looking to continue to expand into new tumor types as well and clearly move into earlier lines of therapy where we believe we can start to move to a point that we can actually give people an extension of life and hopefully, someday get to a point that we talk about cancer as chronic disease, not a fatal disease. Obviously, we have more to do there. But that is the aspiration. And we have a lot of efforts underway to do that, through what we're doing in IO combinations, IO ADC combinations with our subcutaneous offering.

我們需要深化和推動更好的回應。我們希望通過組合和其他方式來做到這一點，以找到改進 KEYTRUDA 的方法。我們也希望繼續擴展到新的腫瘤類型，並明確進入早期治療線，我們相信我們可以開始發展到可以真正延長人們生命的地步，並希望有一天能達到一點，我們將癌症視為慢性疾病，而不是致命疾病。顯然，我們在那裡還有更多工作要做。但這就是願望。通過我們在 IO 組合、IO ADC 組合與我們的皮下產品方面所做的工作，我們正在為此付出很多努力。

And then obviously, we're very excited recently about the deal we did with Moderna for the personalized cancer vaccine, which is really a therapeutic that we think, in combination with KEYTRUDA, while we're studying it first in melanoma obviously, we believe, has the potential to move into broader tumor. So that in and of itself gives us a lot of confidence. And we're doing similar activities with Lynparza with Lenvima and obviously, WELIREG is in its early days.

然後很明顯，我們最近對我們與 Moderna 就個性化癌症疫苗所做的交易感到非常興奮，我們認為這確實是一種治療方法，與 KEYTRUDA 相結合，而我們顯然首先在黑色素瘤中研究它，我們相信，有可能進入更廣泛的腫瘤。所以這本身就給了我們很大的信心。我們正在與 Lynparza 和 Lenvima 進行類似的活動，顯然， WELIREG 處於早期階段。

So if you look at the total of that, and I have even gotten into our vaccines portfolio and what we see as excitement there, we feel like we've made a lot of progress. We have more to do, but that's why you hear me talk more about how do we build the sustainable engine to drive growth well into the next decade. And that really should be our focus point because I'm confident if we do that well, the LOE of KEYTRUDA will take care of itself. So Dean?

因此，如果你看看總的來說，我什至已經進入了我們的疫苗組合，我們在那裡看到了令人興奮的東西，我們覺得我們已經取得了很大的進步。我們還有更多工作要做，但這就是為什麼你聽到我更多地談論我們如何建立可持續發展的引擎來推動下一個十年的增長。這真的應該成為我們的重點，因為我相信如果我們做得好， KEYTRUDA 的 LOE 會照顧好自己。所以院長？

Yes. So there was a question on our TIGIT program, KEYTRUDA plus TIGIT. Just to remind everyone, we have 9 ongoing trials. We have 5 Phase IIIs. In fact, just recently in December, we opened up KEYVIBE-10, which is Phase III and in early melanoma. In relationship to KEYVIBE-003, which I think is the question, we added the TPS greater than 50% as an endpoint, these are event driven. And as the events drive to statistically and clinically meaningful data, we'll announce it appropriately.

是的。所以有一個關於我們的 TIGIT 程序的問題，KEYTRUDA 加 TIGIT。提醒大家，我們正在進行 9 項試驗。我們有 5 個 III 期。事實上，就在最近的 12 月，我們開放了 KEYVIBE-10，這是 III 期和早期黑色素瘤。關於我認為是問題的 KEYVIBE-003，我們添加了大於 50% 的 TPS 作為端點，這些是事件驅動的。隨著事件推動產生具有統計和臨床意義的數據，我們將適當地宣布它。

Thank you, Andrew. Next question, please, Kelly.

謝謝你，安德魯。下一個問題，請凱利。

Our next question comes from Evan Seigerman from BMO.

我們的下一個問題來自 BMO 的 Evan Seigerman。

I would love for you to talk to what might make MK-2870 a better TROP2 targeting ADC versus those that we've seen from Gilead and Astra and Daiichi? Also, do you still believe that it's too difficult to combine an ADC plus IO in a fixed dose combination?

我希望您能談談是什麼使 MK-2870 成為更好的 TROP2 靶向 ADC，而不是我們從 Gilead、Astra 和 Daiichi 看到的那些？另外，您是否仍然認為在固定劑量組合中組合 ADC 和 IO 太難了？

Yes. So let me just state, we'll be starting a whole series of Phase III trials this year. I really appreciate your question. For me, the critical thing is whether it be an ADC or whether it be a RAS inhibitor in solid tumors, especially as you want to advance them in solid tumors where IO has been important, the combination benefit of the 2 becomes really important.

是的。所以我只想說，我們今年將開始一系列的 III 期試驗。我真的很感謝你的問題。對我來說，關鍵是它是實體瘤中的 ADC 還是 RAS 抑製劑，尤其是當你想在 IO 很重要的實體瘤中推進它們時，兩者的聯合優勢變得非常重要。

So we're very excited to be pushing forward our TROP2 ADC. I can get into the details of the molecules, on the linkers and the payloads and the DARs. But really, the better sort of thing is I believe that this year, we will be presenting our Phase II studies. And at the end of the day, that will be the most convincing data to provide to you as to why we think we have an important play with our TROP2 ADC, but it's also the play of that TROP2 ADC in relationship to adding it to an IO agent. We think that is an important considerations when thinking about any cancer-killing mechanism in solid tumors.

所以我們很高興能夠推進我們的 TROP2 ADC。我可以深入了解分子的細節、連接器、有效載荷和 DAR。但實際上，更好的事情是我相信今年，我們將展示我們的 II 期研究。歸根結底，這將是向您提供的最有說服力的數據，說明為什麼我們認為我們的 TROP2 ADC 有重要作用，但它也是 TROP2 ADC 的作用與將其添加到IO代理。我們認為，在考慮實體瘤中的任何癌症殺傷機制時，這是一個重要的考慮因素。

Great. Thank you, Evan. Next question please, Kelly.

偉大的。謝謝你，埃文。下一個問題，凱利。

Our next question comes from Louise Chen from Cantor.

我們的下一個問題來自 Cantor 的 Louise Chen。

So wanted to know how you're thinking about your Phase III trial design for your oral PCSK9? And how will that design really highlight the competitive advantages of your product?

所以想知道您如何考慮口服 PCSK9 的 III 期試驗設計？該設計將如何真正突出您產品的競爭優勢？

Thank you very much. So first, I don't want to get ahead too much of our March 6 Investor Meeting where we're least showing the data that we have in relationship to the oral PCSK9 and sotatercept.

非常感謝你。因此，首先，我不想在我們 3 月 6 日的投資者會議上取得太多進展，在該會議上我們至少展示了與口服 PCSK9 和 sotatercept 相關的數據。

I will just sort of emphasize what we're trying to accomplish. And what we're trying to accomplish is we are trying to accomplish the most potent LDL lowering oral pill for lowering cholesterol. There should be no co-chain, there should be very little need to interact with the health care system, which makes it reach very easy and very accessible, not just in the U.S. but globally. And we need to do it at a price point of what I would call a branded oral medicine would be, not a -- in order to maximize the access.

我只是強調一下我們正在努力完成的事情。我們正在努力完成的是我們正在努力完成最有效的降低 LDL 的口服藥丸以降低膽固醇。應該沒有共同鏈，應該很少需要與醫療保健系統進行交互，這使得它不僅在美國而且在全球範圍內都非常容易和非常容易獲得。我們需要以我所說的品牌口服藥物的價格點來做，而不是——為了最大限度地獲得。

In relationship with Phase III, there's a general set sort of view of how that is. One is you would drive it because LDL lowering is such a clean biomarker, so that's something. But one would also have to, at the same time, drive towards outcomes, which is also going to be important. So our Phase III trial design is informed by what the history of the field has been and what the FDA's regulatory sort of outline comes in for others.

關於第三階段的關係，有一種普遍的看法。一個是你會推動它，因為低密度脂蛋白降低是一種非常乾淨的生物標誌物，所以就是這樣。但與此同時，人們還必須努力取得成果，這也很重要。因此，我們的 III 期試驗設計是根據該領域的歷史以及 FDA 對其他人的監管大綱進行的。

Great. Thank you, Louise. Next question, please, Kelly.

偉大的。謝謝你，路易絲。下一個問題，請凱利。

Next question comes from Tim Anderson from Wolfe Research.

下一個問題來自 Wolfe Research 的 Tim Anderson。

If I could ask you a question on V940, the cancer vaccine. What tumor types outside of melanoma do you already have any positive human data and even if those are earlier stage? And if you don't have any human data in non-melanoma tumor types, can you talk about animal data? I'm trying to obviously think about what Phase III trials you may be starting in 2023 with that product.

如果我可以問你一個關於癌症疫苗 V940 的問題。除了黑色素瘤之外，還有哪些腫瘤類型你已經有任何積極的人類數據，即使那些是早期階段？如果您沒有非黑色素瘤腫瘤類型的任何人類數據，您能談談動物數據嗎？我正在努力考慮您可能會在 2023 年開始使用該產品進行哪些 III 期試驗。

Thank you very much. So you're speaking about the wonderful partnership that we have with Moderna in the personalized cancer vaccine. I just want to preface everything. What we've released is top line data in melanoma. That data will be presented sometime in the near term where we present the data that we have for melanoma. And we have work to do to move that into Phase III.

非常感謝你。所以你說的是我們與 Moderna 在個性化癌症疫苗方面的美妙合作。我只想為一切做序。我們發布的是黑色素瘤的頂級數據。該數據將在近期的某個時候提供，屆時我們將提供我們擁有的黑色素瘤數據。我們還有工作要做才能將其轉移到第三階段。

So we have a lot of work to do just in melanoma. I'm not going to speak ahead of what human data we have outside of that. But I would say 2 things that are really important. One is one can watch which of the tumors have sensitivity to an immune approach. And one can watch about the clinical development with KEYTRUDA to sort of map out where you would think about doing that.

所以我們在黑色素瘤方面還有很多工作要做。我不會提前談論我們擁有的人類數據。但我會說兩件非常重要的事情。一個是可以觀察哪些腫瘤對免疫方法敏感。人們可以通過 KEYTRUDA 觀察臨床開發，以規劃出你會考慮這樣做的地方。

The second issue that I would emphasize is that when we're talking about an IO-IO strategy, which often people speak about, I view this personalized neoantigen therapy as an IO-IO strategy with KEYTRUDA. And the reason I want to emphasize that is there is a view that we are beginning to develop that IO-IO strategies may be especially useful in early cancer stages. And you see that in our interest in our combination projects related to checkpoint inhibitors, but also in relationship to personalized neoantigen therapy.

我要強調的第二個問題是，當我們談論人們經常談論的 IO-IO 策略時，我將這種個性化的新抗原療法視為 KEYTRUDA 的 IO-IO 策略。我想強調的原因是，有一種觀點認為我們正在開始開發 IO-IO 策略可能在早期癌症階段特別有用。你看到我們對與檢查點抑製劑相關的聯合項目感興趣，但也與個性化新抗原治療相關。

And so we think that, that's -- around that, we are going to advance. And the critical component for us to be able to advance that is to advance KEYTRUDA as a monotherapy in indications because it creates us to actually do these clinical trials.

因此，我們認為，那就是 - 圍繞這一點，我們將取得進展。我們能夠推進的關鍵組成部分是將 KEYTRUDA 作為適應症的單一療法推進，因為它使我們能夠真正進行這些臨床試驗。

Great. Thank you, Tim. Next question, please, Kelly.

偉大的。謝謝你，蒂姆。下一個問題，請凱利。

Our next question comes from Geoff from Bank of America.

我們的下一個問題來自美國銀行的傑夫。

Dean, on subcu KEYTRUDA, can you talk about the cadence of data this year and what you're ultimately looking for from a risk/benefit perspective as you evaluate different technologies? And Rob, I wasn't sure where this program ranks on kind of your strategic priorities across IO.

Dean，在 subcu KEYTRUDA 上，你能談談今年數據的節奏，以及你在評估不同技術時從風險/收益的角度最終尋找什麼嗎？ Rob，我不確定這個項目在你整個 IO 的戰略優先事項中的排名。

So thank you very much for that question. I think it's on -- we'll be -- when we talk about starting 10 to 15 Phase III clinical trials, just in oncology, this subcu program is a critical component to that. And we will be starting those Phase III this year. What are we seeking to achieve? I've talked about the early cancer space. The early cancer space, I think, is really important just from a medical standpoint of where we can impact really the outcomes of patients, we can markedly improve that.

非常感謝你提出這個問題。我認為它正在——我們將會——當我們談論開始 10 到 15 項 III 期臨床試驗時，僅在腫瘤學方面，這個 subcu 計劃是其中的一個關鍵組成部分。我們將在今年開始這些第三階段。我們要達到什麼目的？我已經談到了早期癌症領域。我認為，從醫學的角度來看，早期癌症領域非常重要，因為我們可以真正影響患者的預後，我們可以顯著改善這一點。

If you're going to go in the early space, whether it's neoadjuvant or adjuvant, from my clinical training, working with lung cancer doctors and oncologists, our ability to limit the need for individuals to constantly come to infusion centers is very important. And we need to have the scientific innovation to do that.

如果你打算進入早期空間，無論是新輔助還是輔助，從我的臨床培訓，與肺癌醫生和腫瘤學家的合作來看，我們限制個人不斷來到輸液中心的需求的能力非常重要。我們需要有科學創新來做到這一點。

In doing that, we have to think carefully about how do we give as much optionality Q 3 weeks, Q weeks in that subcu regimen, and that's what we're trying to drive through in our Phase III trials. Rob, did you want to answer anything else?

在這樣做的過程中，我們必須仔細考慮我們如何在 subcu 方案中提供盡可能多的 Q 3 週、Q 週，這就是我們在 III 期試驗中試圖推動的。 Rob，你還想回答其他問題嗎？

No, I appreciate the question, Jeff. I think Dean covered it well. This is a very important part of our overall strategy as we think about moving into earlier lines of therapy and then to drive convenience and access for patients, which is -- it's very important. So it's meaningful and it's something we're going to pursue as fast as we can.

不，我很欣賞這個問題，傑夫。我認為 Dean 講得很好。這是我們整體戰略的一個非常重要的部分，因為我們考慮進入更早的治療線，然後為患者提供便利和訪問，這是非常重要的。所以這是有意義的，這是我們將盡快追求的目標。

Thanks, Geoff. Next question, please, Kelly.

謝謝，傑夫。下一個問題，請凱利。

Next question comes from Mohit Bansal from Wells Fargo.

下一個問題來自富國銀行的 Mohit Bansal。

I think I have a big-picture question regarding IO-IO combinations and the development strategy there. Because the common criticism is that many of these big Phase III studies were started with -- after less-than-robust Phase II data, and that's why they failed to show benefit in Phase III.

我想我有一個關於 IO-IO 組合和那裡的開發策略的大問題。因為普遍的批評是，許多這些大型 III 期研究是在 II 期數據不那麼可靠之後開始的，這就是為什麼它們未能在 III 期顯示出益處。

I mean looking at your data in Phase II, they are single-arm data as well. So can you just help us understand what gives you confidence that this is the right strategy to move forward? And wouldn't it be better to do some kind of Phase II trial where you have pembro as a control?

我的意思是看你二期的數據，也是單臂數據。那麼，您能否幫助我們了解是什麼讓您相信這是前進的正確戰略？做一些以 pembro 作為對照的 II 期試驗不是更好嗎？

Yes. Thank you very much. I'll just emphasize that as a general rule, the way that I have begun to develop my view of IO-IO strategies is that IO-IO strategies are very important to pursue. I think that IO-IO strategies plus other therapies that kill cancers may be especially important in the metastatic. But IO-IO strategies in the early stage could be quite impactful.

是的。非常感謝你。我只是強調，作為一般規則，我開始發展我對 IO-IO 策略的看法的方式是，IO-IO 策略是非常重要的。我認為 IO-IO 策略加上其他殺死癌症的療法可能在轉移中尤為重要。但早期的 IO-IO 策略可能會非常有影響力。

And so as I've just said, we have advanced our IO-IO strategy. We've advanced it with TIGIT CTLA-4 and LAG-3, so another component part. But I would just say that I don't know that there's 1 single addition to KEYTRUDA that will have the breadth of KEYTRUDA, so we've been a little bit selective there.

正如我剛才所說，我們已經推進了 IO-IO 戰略。我們用 TIGIT CTLA-4 和 LAG-3 對它進行了改進，這是另一個組成部分。但我只想說，我不知道 KEYTRUDA 中是否有 1 個單一的附加項具有 KEYTRUDA 的廣度，所以我們在那裡有點選擇性。

And I think the movement of IO-IO, not just in the metastatic space but especially in the early space will become important. And the ability to do that requires your first IO of that IO-IO to be approved in the early space. And that is why we are so excited about moving into earlier spaces with KEYTRUDA, because that allows us to execute in an IO-IO strategy in early-stage cancers.

而且我認為 IO-IO 的運動，不僅在轉移空間，而且尤其是在早期空間，都將變得重要。而要做到這一點，就需要您在早期空間中批准該 IO-IO 的第一個 IO。這就是為什麼我們對使用 KEYTRUDA 進入早期領域感到非常興奮，因為這使我們能夠在早期癌症中執行 IO-IO 策略。

Thanks, Mohit. Next question, please, Kelly.

謝謝，莫希特。下一個問題，請凱利。

Our next question comes from Chris Schott from JPMorgan.

我們的下一個問題來自摩根大通的 Chris Schott。

I think you mentioned that you're looking to review share repo. And it does seem like maybe, Rob, some of your recent business development commentary has been skewed towards smaller deals or collaboration. So can you all just put into context what you view as an appropriate level of leverage for Merck? And should we be thinking about kind of the cash generation beyond that level as maybe going towards repo going forward?

我想你提到過你正在尋找審查股票回購協議。 Rob，您最近的一些業務發展評論似乎確實偏向於較小的交易或合作。那麼你們能不能把你們認為對默克來說合適的槓桿水平放在上下文中？我們是否應該考慮超出該水平的現金產生方式，可能會在未來進行回購？

And let me just slip a really quick second one. Just help me on FX. I think you were talking about a 2% headwind. Most of your peers aren't seeing much given the recent weakening of the dollar. Are there any currencies that stand out we should be keeping in mind there?

讓我再說一個非常快的第二個。幫我解決外匯問題。我想你說的是 2% 的逆風。鑑於最近美元走軟，您的大多數同行都沒有看到太多。有沒有什麼貨幣是我們應該牢記的？

So Chris, this is Caroline. First to talk to share repurchase. As we've stated previously, it's our goal as a company to deploy our cash, first and foremost, behind the business opportunities we have within the company as well as augment that with business development. We have turned on the share repurchase program, given the strength of our business and our balance sheet. But we'll be ensuring we have ample capacity to pursue business development, which is the highest priority and is a better generator of growth and value creation.

克里斯，這是卡羅琳。先說股份回購。正如我們之前所說，作為一家公司，我們的目標是首先部署我們的現金，以支持我們在公司內部擁有的商業機會，並通過業務發展來增加這種機會。鑑於我們的業務實力和資產負債表，我們已經啟動了股票回購計劃。但我們將確保我們有足夠的能力來追求業務發展，這是重中之重，也是增長和價值創造的更好動力。

We have a portfolio of BDs that we are reviewing, and we will continue to do so and hope to have news that we'll be sharing in the future. So priority remains BD, invest in the business, but to the extent there is excess cash, we will return that to shareholders through the share buybacks. We will maintain an appropriate leverage for our company. We are very comfortable operating at the credit rating we are at, and would expect to sustain that kind of level as we go forward.

我們有一個正在審查的 BD 組合，我們將繼續這樣做，並希望有我們將在未來分享的消息。所以優先事項仍然是 BD，投資於業務，但如果有多餘的現金，我們將通過股票回購將其返還給股東。我們將為公司保持適當的槓桿作用。我們對我們目前的信用評級運營感到非常滿意，並希望在我們前進的過程中保持這種水平。

From a foreign exchange perspective, in 2022, we were extremely successful as a company in blunting the impact of foreign exchange with our revenue hedging program. The underlying impact of foreign exchange to our business in 2022 was approximately 6% on the top line, 10% on the bottom line. But with our effective hedging program, which brought revenue on the other revenue line of approximately $800 million, that blunted the impact to 4% on the top and 4% on the bottom.

從外彙的角度來看，2022 年，作為一家公司，我們通過收入對沖計劃成功地削弱了外彙的影響。 2022 年外匯對我們業務的潛在影響約為 6% 的收入，10% 的收入。但是，通過我們有效的對沖計劃，該計劃為另一條收入線帶來了約 8 億美元的收入，將影響降低到最高 4% 和最低 4%。

As you rightly note, as we look at 2023, we expect the underlying impact of foreign exchange to be around 1 percentage point on the top and the bottom line. What is impacting the guidance that we've given is we obviously don't expect as significant hedge gains in 2023, which means that the overall impact from foreign exchange year-over-year is expected to be 2% on the top and 4% on the bottom.

正如您正確指出的那樣，展望 2023 年，我們預計外彙的潛在影響將在頂部和底部產生約 1 個百分點的影響。影響我們給出的指引的是，我們顯然預計 2023 年不會出現顯著的對沖收益，這意味著外彙的總體影響預計同比增長 2% 和 4%在底部。

Great. Thank you, Chris. Next question, please, Kelly.

偉大的。謝謝你，克里斯。下一個問題，請凱利。

Our next question comes from Terence Flynn from Morgan Stanley.

我們的下一個問題來自摩根士丹利的特倫斯弗林。

I know you guys typically don't give product level guidance, Caroline, but I was wondering if you can speak at a high level about your vaccine franchise this year. Obviously, you have new capacity coming out for GARDASIL, but you also talked about the pediatric opportunity for VAXNEUVANCE. So just wondering how we should think about those this year.

我知道你們通常不會提供產品級別的指導，Caroline，但我想知道你今年是否可以在高層次上談論你們的疫苗特許經營權。顯然，您有 GARDASIL 的新能力，但您也談到了 VAXNEUVANCE 的兒科機會。所以只是想知道今年我們應該如何考慮這些。

And then 1 follow-up for Dean on sotatercept. I know you're talking to the FDA now. Are you still confident that, that single trial will be sufficient for approval? Or is there a possibility you could need data from the other ongoing studies?

然後是 Dean 對 sotatercept 的 1 次跟進。我知道你現在正在與 FDA 交談。您是否仍然相信，單次試驗就足以獲得批准？或者您是否可能需要來自其他正在進行的研究的數據？

Thank you for the question. So the guidance that we've provided for 2023 is underpinned by very strong revenue growth of 7% to 10% when you exclude the impact of LAGEVRIO and foreign exchange. The drivers of that growth are our key pillars of oncology, where we expect continued impact to patients and growth, given the portfolio of indications we have in KEYTRUDA, Lynparza, Lenvima.

感謝你的提問。因此，當您排除 LAGEVRIO 和外彙的影響時，我們為 2023 年提供的指導以 7% 至 10% 的非常強勁的收入增長為基礎。這種增長的驅動力是我們腫瘤學的關鍵支柱，鑑於我們在 KEYTRUDA 、 Lynparza 、 Lenvima 的適應症組合，我們預計對患者和增長的持續影響。

Vaccines, as you rightly note, driven by an acceleration expected in the growth of GARDASIL as we have new supply coming online as well as an acceleration in our VAXNEUVANCE performance, especially given the strong data we have for the pediatric setting.

疫苗，正如您正確指出的那樣，受到 GARDASIL 增長預期的加速推動，因為我們有新的供應上線以及我們的 VAXNEUVANCE 性能加速，特別是考慮到我們在兒科環境中的強大數據。

And we expect continued growth, strong growth in our Animal Health business. There are some headwinds against that, that we've talked about with LAGEVRIO, with foreign exchange and with an increased level of pricing expected, especially in Europe with the changes to the BPA Scheme that U.K. and AMNOG in Germany. But overall, very confident in the underlying growth of our business anchored to oncology, vaccines and Animal Health.

我們預計我們的動物保健業務將持續增長，強勁增長。有一些不利因素，我們已經與 LAGEVRIO 討論過，外彙和預期定價水平的提高，特別是在歐洲，英國和德國的 AMNOG 改變了 BPA 計劃。但總的來說，我們對我們以腫瘤學、疫苗和動物保健為基礎的業務的潛在增長非常有信心。

Yes. So again, March 6, clinical trial data for sotatercept will be more fully discussed. I think it will be very impactful data. And I have no indication at this point that we will need a readout from any other trial from a clinical standpoint to support our filing to the FDA for sotatercept.

是的。因此，3 月 6 日，sotatercept 的臨床試驗數據將再次得到更充分的討論。我認為這將是非常有影響力的數據。在這一點上，我沒有跡象表明我們需要從臨床角度的任何其他試驗的讀數來支持我們向 FDA 提交 sotatercept。

Thank you, Terence. Next question, please, Kelly.

謝謝你，特倫斯。下一個問題，請凱利。

Our next question comes from Colin Bristow of UBS.

我們的下一個問題來自瑞銀的 Colin Bristow。

I guess I'll piggyback on a couple of the others. On TIGIT, we've obviously seen some competitive data recently, and then we have some Phase III competitor readout this year. Just what is your level of enthusiasm for this class currently? And just what underpins that in terms of the data we've seen?

我想我會搭載其他幾個。在 TIGIT 上，我們最近顯然看到了一些競爭數據，然後我們今年有一些 III 期競爭對手的數據。您目前對這門課的熱情如何？就我們所看到的數據而言，是什麼支撐了這一點？

And then just second on GARDASIL, are you able to give any more granularity on the timing and levels of additional supply that will be coming online with respect to the new manufacturing facility?

然後僅次於 GARDASIL，您能否更詳細地說明與新製造工廠相關的額外供應的時間和水平？

Yes. Well, thank you for that question. In relationship to TIGIT, I mean, we're very confident in our molecule. As I've said, we have 9 ongoing, 5 Phase III trials pushing the boundaries of what pembro can do or PD-1 can do with another IO agent has been something that's very important for the field. And the way that I can simply answer your question about the confidence in the molecule is we just opened an additional KEYVIBE study, a Phase III study in the earlier stages of cancer for this IO-IO combination.

是的。好吧，謝謝你提出這個問題。關於 TIGIT，我的意思是，我們對我們的分子非常有信心。正如我所說，我們有 9 個正在進行的 5 個 III 期試驗，突破了 pembro 可以做什麼或 PD-1 可以用另一種 IO 代理做什麼的界限，這對該領域非常重要。我可以簡單地回答你關於對分子的信心的問題的方式是我們剛剛開展了一項額外的 KEYVIBE 研究，這是針對這種 IO-IO 組合的癌症早期階段的 III 期研究。

And for GARDASIL, we, as you know, have driven productivity in the existing manufacturing facilities we have. And we have 2 new facilities coming online over the course of '23, '24. So it will be a progressive ramp, but I'll reiterate we're expecting an acceleration in our growth during 2023.

對於 GARDASIL，如您所知，我們已經提高了現有製造設施的生產率。在 23 年和 24 年期間，我們有 2 個新設施上線。所以這將是一個漸進的斜坡，但我要重申，我們預計我們的增長將在 2023 年加速。

Great. Thank you, Colin. Next question, please, Kelly.

偉大的。謝謝你，科林。下一個問題，請凱利。

Our next question comes from Umer Raffat from Evercore.

我們的下一個問題來自 Evercore 的 Umer Rafat。

There was a story in New York Times last week, which mentioned Merck has a patent estate of 180 patents on KEYTRUDA. And I'm curious, since your 10-K only points to the earliest patent expiry date of 2028, can you speak to the types of patents encompassed in this 180 patent estate? And is it reasonable to assume that your true patent estate on KEYTRUDA goes well past 2035?

紐約時報上周有一篇報導，提到默克公司在 KEYTRUDA 上擁有 180 項專利。我很好奇，由於您的 10-K 僅指出最早的專利到期日期為 2028 年，您能否談談這 180 項專利財產中包含的專利類型？並且假設您在 KEYTRUDA 上的真實專利資產已經超過 2035 年是否合理？

Yes. So I would just want to elevate the question a little bit. The focus of what we're trying to do is we're trying to drive the concept of inhibition of checkpoint inhibitors can really have a profound effect throughout cancers in all stages, in all tumor types. We talk about expand into different tissue types and stages, deepen in combination and extend with routes of delivery, roots of [administration] and frequency.

是的。所以我只想稍微提升一下這個問題。我們正在努力做的重點是，我們正在努力推動抑制檢查點抑製劑的概念真正對所有階段、所有腫瘤類型的癌症產生深遠影響。我們談論擴展到不同的組織類型和階段，加深組合併擴展遞送途徑、 [給藥] 的根源和頻率。

And these innovations are critically important to make sure that this life-saving sort of treatment is available. And we are confident in those innovations providing benefit to patients. And we have filed, where appropriate, intellectual property for it, for that.

這些創新對於確保這種挽救生命的治療方法的可用性至關重要。我們對那些為患者帶來益處的創新充滿信心。為此，我們已在適當的情況下為其申請了知識產權。

Thank you, Umer. Last question, please, Kelly.

謝謝你，烏默爾。最後一個問題，凱利。

Our last question comes from Steve Scala from Cowen.

我們的最後一個問題來自 Cowen 的 Steve Scala。

Novartis said yesterday that it believes the treatment of cardiovascular disease is moving towards infrequently administered injectables as opposed to orals, citing very poor compliance with orals. They probably have a good point because the Merck PCSK9 could be associated with GI issues and other issues, which may make oral delivery a challenge. So I assume you disagree. Is that because indeed, your oral PCSK9 is very well tolerated and clean? Or do you disagree for other reasons?

諾華昨天表示，它認為心血管疾病的治療正在轉向不經常使用的注射劑，而不是口服藥物，理由是口服藥物的依從性非常差。他們可能有一個很好的觀點，因為默克 PCSK9 可能與胃腸道問題和其他問題有關，這可能使口服給藥成為一項挑戰。所以我假設你不同意。那是因為您的口腔 PCSK9 確實具有很好的耐受性和清潔性嗎？還是因為其他原因不同意？

We'll be talking about the detailed data from the PCSK9. We believe that it's very clean. But I'll just step back, as a cardiologist who trained in the late '80s and 1990s, the ability to have an oral drug that lowered LDL cholesterol was impactful for the world.

我們將討論來自 PCSK9 的詳細數據。我們相信它非常乾淨。但我會退後一步，作為一名在 80 年代末和 1990 年代接受培訓的心髒病專家，擁有降低低密度脂蛋白膽固醇的口服藥物的能力對世界產生了影響。

Yes, every oral drug, regardless of what therapy it is, has a compliance, so it's very important to maintain compliance. What we're trying to do is to create the most potent LDL cholesterol lowering pill ever made that does not require, does not require constant interactions with a health care system. We think that, that axis is actually one that's very important, not just in the U.S., but also globally.

是的，每一種口服藥物，不管是什麼療法，都有依從性，所以保持依從性非常重要。我們正在嘗試做的是創造有史以來最有效的降低低密度脂蛋白膽固醇的藥丸，它不需要，不需要與醫療保健系統的持續互動。我們認為，這個軸心實際上是一個非常重要的軸心，不僅在美國，而且在全球範圍內。

And this is personally speaking, as someone who practice this early, as recently as 5 years ago. If I had an oral PCSK9 LDL lowering pill back then, I would be prescribing it with the other 3 to 4 oral pills that I'm prescribing an individual.

這是就我個人而言，作為一個早早練習的人，最近 5 年前。如果當時我有一種口服 PCSK9 LDL 降低藥丸，我會把它和我開給個人的其他 3 到 4 種口服藥一起開。

Thank you, Steve, and thank you, everybody, for your thoughtful questions. Please follow up with me and the IR team if you have anything additional, and we look forward to staying in touch. Take care.

謝謝你，史蒂夫，也謝謝大家提出的深思熟慮的問題。如果您有任何其他問題，請與我和 IR 團隊聯繫，我們期待與您保持聯繫。小心。

That concludes today's call. Thank you for participating. You may disconnect at this time.

今天的電話會議到此結束。感謝您的參與。此時您可以斷開連接。