默克藥廠 (MRK) 2023 Q1 法說會逐字稿

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

謝謝你的支持。歡迎參加默克公司第一季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 First Quarter 2023 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 2023 年第一季度電話會議。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. 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. Our SEC filings, including Item 1A and 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. Merck undertakes no obligation to publicly update any forward-looking statements.

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。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。我們向美國證券交易委員會提交的文件，包括項目 1A 和 2022 10-K，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. 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.

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。這些幻燈片連同收益發布、今天準備好的評論和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. We began 2023 with significant advancements across key areas of our pipeline and with continued strong performance of our key growth drivers. I remain very pleased with the consistency and excellence of our team's execution, and I'm confident that our strategy is leading to sustainable success. We remain grounded in our shared purpose to bring forward bold science that delivered solutions, which address serious unmet medical needs and importantly, save and improve lives around the world.

謝謝，彼得。早上好，感謝您參加今天的電話會議。 2023 年伊始，我們在管道的關鍵領域取得了重大進展，並且我們的主要增長動力繼續保持強勁表現。我仍然對我們團隊執行的一致性和卓越性感到非常滿意，並且我相信我們的戰略正在帶來可持續的成功。我們始終立足於我們的共同目標，即提出大膽的科學，提供解決方案，解決嚴重未滿足的醫療需求，重要的是，拯救和改善世界各地的生活。

Our priorities remain consistent. By focusing on our science-led strategy, we intend to bring forward important innovation from our internal discovery pipeline and via strategic business development targeted at accessing the most compelling and complementary external science, leveraging our best-in-class clinical development capabilities. We aim to sustain the momentum in our pipeline in 2023 and beyond, and we're confident that this will lead to strong commercial and financial performance as well as value creation for patients and shareholders over the long term.

我們的優先事項保持一致。通過專注於我們以科學為主導的戰略，我們打算通過我們的內部發現管道和戰略業務發展帶來重要的創新，旨在利用我們一流的臨床開發能力，以獲取最引人注目和互補的外部科學。我們的目標是在 2023 年及以後保持我們管道的勢頭，我們相信這將帶來強勁的商業和財務業績，並長期為患者和股東創造價值。

Speaking of accessing important external innovation, we're very pleased with our announced acquisition of Prometheus Biosciences. Prometheus brings us a potential best-in-class novel treatment that could transform the standard of care for patients suffering from ulcerative colitis and Crohn's disease, potentially debilitating conditions as well as a broader pipeline and a technology platform that enables a precision medicine approach. It accelerates our presence in immunology, increases the diversity of our pipeline and brings us a potentially significant revenue growth driver through the next decade. This transaction is also another example of Merck acting decisively when science and value align.

談到獲得重要的外部創新，我們對宣布收購 Prometheus Biosciences 感到非常高興。 Prometheus 為我們帶來了一種潛在的一流新療法，它可以改變患有潰瘍性結腸炎和克羅恩病、可能使人衰弱的疾病的患者的護理標準，以及更廣泛的管道和技術平台，從而實現精準醫學方法。它加速了我們在免疫學領域的存在，增加了我們管道的多樣性，並為我們帶來了未來十年潛在的重要收入增長動力。此次交易也是默克在科學與價值一致時果斷行事的又一例證。

Turning now to our first quarter results. We delivered very significant underlying growth, excluding the expected year-over-year decline in LAGEVRIO sales. This reflects continued fundamental strength and momentum across our key growth drivers particularly in oncology and vaccines. These results reinforce our confidence in the robust demand for our innovative portfolio and in our outlook for the remainder of 2023, which Caroline will speak to in a moment.

現在轉向我們的第一季度業績。我們實現了非常顯著的基礎增長，不包括 LAGEVRIO 銷售額的預期同比下降。這反映了我們主要增長驅動因素的持續基本實力和勢頭，尤其是在腫瘤學和疫苗領域。這些結果增強了我們對我們創新產品組合的強勁需求以及我們對 2023 年剩餘時間的展望的信心，Caroline 稍後將對此發表講話。

Moving to our research organization. We've made significant advancements. In cardiovascular, we shared the remarkable work of our research colleagues at the American College of Cardiology Conference in March. The strength of the data from the Phase III STELLAR trial studying sotatercept in pulmonary arterial hypertension reinforces our belief in this important new mechanisms potential to change the treatment paradigm for patients.

轉到我們的研究機構。我們取得了重大進展。在心血管方面，我們在 3 月份的美國心髒病學會會議上分享了研究同事的傑出工作。研究肺動脈高壓中 sotatercept 的 III 期 STELLAR 試驗數據的強度加強了我們對這一重要的新機制可能改變患者治療模式的信念。

In addition, impressive results from the Phase II trial studying our oral PCSK9 inhibitor suggests that this could be a globally accessible treatment option for patients in need of LDL cholesterol reduction.

此外，研究我們口服 PCSK9 抑製劑的 II 期試驗的令人印象深刻的結果表明，對於需要降低低密度脂蛋白膽固醇的患者來說，這可能是一種全球可及的治療選擇。

The successes we are achieving across our cardiovascular pipeline have created excitement across our company and a belief that Merck will build on its strong legacy of bringing forth breakthrough therapies for the benefit of patients suffering from cardiovascular disease and that these programs will contribute significantly to our long-term growth.

我們在心血管領域取得的成功讓整個公司興奮不已，並相信默克將在其強大傳統的基礎上繼續發展，為心血管疾病患者帶來突破性療法，這些項目將為我們的長期發展做出重大貢獻。 -長期增長。

In oncology, we were pleased to share the positive top line results from KEYNOTE-671, which showed a significant improvement in event-free survival in certain patients with early-stage non-small cell lung cancer, and we look forward to potential approval later this year. In addition, we are working with our partner, Moderna to rapidly expand our efforts to study the combination of KEYTRUDA with an individualized neoantigen therapy, which we previously referred to as a personalized cancer vaccine therapy in adjuvant melanoma and potential additional tumor types.

在腫瘤學方面，我們很高興分享 KEYNOTE-671 的正面頂線結果，該結果顯示某些早期非小細胞肺癌患者的無事件生存期顯著改善，我們期待以後可能獲得批准今年。此外，我們正在與我們的合作夥伴 Moderna 合作，迅速擴大我們的努力，研究 KEYTRUDA 與個體化新抗原療法的結合，我們之前將其稱為輔助黑色素瘤和潛在其他腫瘤類型的個體化癌症疫苗療法。

I'm very encouraged by the substantial progress we've made across our broad pipeline. We're now working on a greater number of late-stage programs across more therapeutic areas and modalities than at any time in recent years.

我對我們在廣泛的管道中取得的實質性進展感到非常鼓舞。與近年來的任何時候相比，我們現在正在開展更多治療領域和方式的後期項目。

In summary, we've begun 2023 with scientific, commercial and operational momentum and expect strong full year growth across both our Human and Animal Health businesses. I'm proud of the progress we've made, but as always recognize the need to move with speed and urgency to do even more. I want to thank our global team for their steadfast dedication as we build a sustainable innovation engine that will deliver value for patients and shareholders well into the next decade.

總而言之，我們以科學、商業和運營勢頭開啟了 2023 年，並預計我們的人類和動物健康業務全年將實現強勁增長。我為我們取得的進展感到自豪，但一如既往地認識到需要迅速和緊迫地採取行動以做更多事情。我要感謝我們的全球團隊的堅定奉獻，因為我們建立了一個可持續的創新引擎，它將在未來十年為患者和股東創造價值。

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

有了這個，我會把電話轉給卡羅琳。

Thank you, Rob. Good morning. As Rob highlighted, we are off to a strong start to the year with robust underlying performance across our key growth pillars. These results further demonstrate but our focus on science and innovation as the core of our strategy is working. Our success is enabled by the excellent execution of our team of dedicated colleagues who are delivering our important medicines and vaccines to people and animals across the globe. We remain very confident in our ability to continue to deliver in the short term while we make disciplined investments to maximize long-term value for patients and shareholders.

謝謝你，羅布。早上好。正如 Rob 強調的那樣，我們今年開局強勁，主要增長支柱的基礎表現強勁。這些結果進一步表明，我們以科學和創新為核心的戰略正在發揮作用。我們的成功得益於我們敬業的同事團隊的出色執行力，他們正在向全球的人和動物提供我們的重要藥物和疫苗。我們仍然對我們在短期內繼續交付的能力充滿信心，同時我們進行有紀律的投資以最大限度地提高患者和股東的長期價值。

Now turning to our first quarter results. Total company revenues were $14.5 billion. Excluding the impact from LAGEVRIO and foreign exchange, the business delivered very strong underlying growth of 15%. The remainder of my revenue comments will be on an ex exchange basis.

現在轉向我們的第一季度業績。公司總收入為 145 億美元。排除 LAGEVRIO 和外彙的影響，該業務實現了 15% 的非常強勁的基礎增長。我的其餘收入評論將以交換為基礎。

Our Human Health business continued its strong momentum, excluding LAGEVRIO, growth was 18%, driven by oncology and vaccines. Our Animal Health business also delivered solid performance with sales increasing 5% and driven by growth across both livestock and companion animal products.

我們的人類健康業務繼續保持強勁勢頭，不包括 LAGEVRIO，在腫瘤學和疫苗的推動下增長了 18%。我們的動物保健業務也取得了穩健的業績，銷售額增長了 5%，這主要得益於家畜和伴侶動物產品的增長。

Now turning to the first quarter performance of our key brands. In oncology, KEYTRUDA grew 24% to $5.8 billion, driven by robust global demand for metastatic indications as well as increased utilization driven by approvals in early-stage cancers. In the U.S., KEYTRUDA grew across all key tumor types and continues 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一季度業績。在腫瘤學領域，KEYTRUDA 增長了 24%，達到 58 億美元，這得益於全球對轉移適應症的強勁需求以及早期癌症批准推動的利用率增加。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。

We continue to anticipate gradual uptake from KEYNOTE-091 in earlier stage lung cancer as we are working with the medical community to increase adjuvant treatment rates for diagnosed patients receiving surgery. We, along with others, are also working to improve upon the low level of lung cancer screenings and follow-up through diagnosis which we anticipate will increase over time. We are encouraged by the positive feedback received thus far.

我們繼續期待 KEYNOTE-091 在早期肺癌中的逐漸應用，因為我們正在與醫學界合作，以提高接受手術的確診患者的輔助治療率。我們和其他人一起也在努力改善低水平的肺癌篩查和診斷隨訪，我們預計這會隨著時間的推移而增加。我們對迄今為止收到的積極反饋感到鼓舞。

Furthermore, we are excited by the potential to bring an additional treatment option to patients following the positive results of the KEYNOTE-671 study. Together, these studies position us well to extend our leadership in non-small cell lung cancer. We also look forward to providing a new treatment option to certain adult patients with bladder cancer following the recent approval of KEYNOTE-869.

此外，我們很高興有可能在 KEYNOTE-671 研究取得積極成果後為患者提供額外的治療選擇。總之，這些研究使我們能夠很好地擴大我們在非小細胞肺癌領域的領導地位。我們也期待在最近批准 KEYNOTE-869 後為某些成年膀胱癌患者提供新的治療選擇。

Outside the U.S. KEYTRUDA continues to maintain its leadership in non-small cell lung cancer. Growth was driven by uptake in metastatic renal cell carcinoma and certain types of head and neck cancer as well as in earlier stage cancers, including certain types of high-risk early-stage triple-negative breast cancer, which continues to launch in additional markets.

在美國以外，KEYTRUDA 繼續保持其在非小細胞肺癌領域的領先地位。增長是由轉移性腎細胞癌和某些類型的頭頸癌以及早期癌症（包括某些類型的高風險早期三陰性乳腺癌）的吸收推動的，這些癌症繼續在其他市場推出。

Lynparza remains the market-leading PARP inhibitor. Alliance revenue grew 8%, primarily due to increased demand in key European markets in certain patients with ovarian cancer. Lenvima alliance revenue grew 5% due to increased uptake in the treatment of certain patients with advanced renal cell carcinoma in key European markets. Our vaccines portfolio delivered excellent growth led by GARDASIL, which grew 43% to $2 billion. Performance was driven by strong demand in major ex-U.S. markets particularly China as well as increased supply. Growth also benefited from an acceleration of shipments to China from the second half to the first half of the year to ensure the availability of product to meet heightened demand following the approval of the expanded indication of GARDASIL 9 for girls and women, 9 to 45 years of age. Vaccine sales also benefited from the increasing demand for VAXNEUVANCE following the ongoing pediatric launch, particularly in the U.S. In our hospital acute care portfolio, BRIDION sales grew 27%, driven by an increase in market share among neuromuscular blockade reversal agents.

Lynparza 仍然是市場領先的 PARP 抑製劑。聯盟收入增長了 8%，這主要是由於歐洲主要市場對某些卵巢癌患者的需求增加。 Lenvima 聯盟的收入增長了 5%，這是由於歐洲主要市場對某些晚期腎細胞癌患者的治療有所增加。我們的疫苗產品組合在 GARDASIL 的帶動下實現了出色的增長，增長 43% 至 20 億美元。業績是由美國以外的主要市場的強勁需求推動的。市場，尤其是中國，以及供應增加。增長還得益於今年下半年到上半年對中國的出貨量加速，以確保產品的可用性能夠滿足 GARDASIL 9 擴大適用於 9 至 45 歲女孩和女性的批准後的高需求年齡。疫苗銷售也受益於 VAXNEUVANCE 持續的兒科上市後需求增加，尤其是在美國。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的推動，BRIDION 銷售額增長了 27%。

Our Animal Health business delivered another good quarter with sales increasing 5%, reflecting strong demand across our livestock portfolio, particularly in ruminant and poultry products as well as strategic price actions.

我們的動物保健業務又迎來了一個不錯的季度，銷售額增長了 5%，反映出我們對牲畜產品組合的強勁需求，尤其是反芻動物和家禽產品以及戰略性價格行動。

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 76.9%, an increase of 6.1 percentage points due to favorable product mix, which reflects a benefit from the lower sales of LAGEVRIO. Operating expenses increased to $6.7 billion, reflecting $1.4 billion of charges related to the acquisition of Imago and our license and collaboration agreement with Kelun. Excluding these charges, operating expenses grew 12%, driven by increased investments to support our key growth drivers and pipeline. Other income was $17 million. Our tax rate was 20.4%, reflecting the unfavorable impact from the Imago transaction for which no tax benefit was recognized. Taken together, we earned $1.40 per share, which includes a $0.52 impact from charges related to the acquisition of Imago and our agreement with Kelun.

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。由於有利的產品組合，毛利率為 76.9%，增長 6.1 個百分點，這反映出受益於 LAGEVRIO 較低的銷售額。運營費用增加到 67 億美元，反映了與收購 Imago 以及我們與科倫的許可和合作協議相關的 14 億美元費用。不包括這些費用，運營費用增長了 12%，這是由於增加投資以支持我們的主要增長動力和管道。其他收入為 1700 萬美元。我們的稅率為 20.4%，反映了未確認稅收優惠的 Imago 交易的不利影響。總的來說，我們每股收益為 1.40 美元，其中包括與收購 Imago 相關的費用以及我們與科倫的協議所產生的 0.52 美元影響。

Turning now to our 2023 non-GAAP guidance. The continued operational strength of our business enables us to raise and narrow our full year revenue guidance. We now project revenue to be between $57.7 billion and $58.9 billion, including approximately $1 billion from LAGEVRIO. We expect strong underlying revenue growth of 8% to 10%, offset by the decline in LAGEVRIO and an approximate 2 percentage point negative impact from foreign exchange using mid-April rates.

現在轉向我們的 2023 年非公認會計原則指南。我們業務的持續運營實力使我們能夠提高和縮小全年收入預期。我們現在預計收入在 577 億美元至 589 億美元之間，其中包括來自 LAGEVRIO 的約 10 億美元。我們預計基礎收入將強勁增長 8% 至 10%，但被 LAGEVRIO 的下降和使用 4 月中旬匯率計算的外匯帶來的約 2 個百分點的負面影響所抵消。

Our gross margin is still expected to be approximately 77%. We have narrowed the estimated range of operating expenses to be between $23.3 billion and $24.1 billion. As a reminder, this range includes $1.4 billion of upfront research and development expenses related to the acquisition of Imago and our agreement with Kelun. This guidance does not assume the proposed acquisition of Prometheus or any additional significant potential business development transactions. Other income is anticipated to be approximately $250 million. We continue to assume a full year tax rate between 17% and 18%, and approximately 2.55 billion shares outstanding. Taken together, we are increasing and narrowing our expected EPS range to $6.88 to $7. This range includes a negative impact from foreign exchange of approximately 4 percentage points using mid-April rates.

我們的毛利率仍預計約為 77%。我們已將運營費用的估計範圍縮小到 233 億美元至 241 億美元之間。提醒一下，這個範圍包括與收購 Imago 相關的 14 億美元前期研發費用以及我們與科倫的協議。本指南不假設擬議收購 Prometheus 或任何其他重要的潛在業務發展交易。其他收入預計約為 2.5 億美元。我們繼續假設全年稅率在 17% 至 18% 之間，流通股約為 25.5 億股。綜上所述，我們將預期每股收益範圍提高和縮小至 6.88 美元至 7 美元。使用 4 月中旬的匯率，該範圍包括外匯帶來的大約 4 個百分點的負面影響。

It is important to note that this guidance does not include the impact of the proposed acquisition of Prometheus, which is expected to close in the third quarter of this year. We expect the transaction will result in a onetime charge that will increase research and development expense of approximately $10.3 billion or approximately $4 per share. The impact of this charge will be reflected in both our GAAP and non-GAAP results. In addition, ongoing investment to advance the pipeline assets as well as the cost of financing will negatively impact EPS by approximately $0.25 in the first 12 months following close.

值得注意的是，本指南不包括擬議收購普羅米修斯的影響，該收購預計將於今年第三季度完成。我們預計該交易將產生一次性費用，這將使研發費用增加約 103 億美元或每股約 4 美元。這筆費用的影響將反映在我們的 GAAP 和非 GAAP 結果中。此外，推進管道資產的持續投資以及融資成本將在收盤後的前 12 個月內對 EPS 產生約 0.25 美元的負面影響。

As Rob noted, we are very excited by Prometheus compelling science and confident that this transaction has the potential to create meaningful value for patients and shareholders. Our guidance reflects our continued confidence in the underlying strength of our business, driven by our key pillars in oncology, vaccines and Animal Health.

正如 Rob 指出的那樣，我們對 Prometheus 引人注目的科學感到非常興奮，並相信這項交易有可能為患者和股東創造有意義的價值。我們的指引反映了我們在腫瘤學、疫苗和動物健康領域的關鍵支柱的推動下，對我們業務的潛在實力的持續信心。

As you consider your models, there are a few items to keep in mind. In the U.S., KEYTRUDA has achieved exceptional growth over the past several quarters driven by recent launches, particularly in early-stage indications, such as triple-negative breast cancer. While we continue to anticipate growth from these earlier-stage indications, the year-over-year growth rate is expected to moderate as we anniversary their very strong initial uptake. Outside the U.S., we continue to expect strong volume growth for KEYTRUDA. However, pricing is an increasing headwind, particularly as we launch new indications in key European markets, which will temper ex-U.S. growth.

當您考慮您的模型時，需要記住一些事項。在美國，KEYTRUDA 在最近幾個季度的推出推動下取得了非凡的增長，特別是在三陰性乳腺癌等早期適應症方面。雖然我們繼續預期這些早期跡象的增長，但隨著我們對它們非常強勁的初步吸收進行週年紀念，預計同比增長率將放緩。在美國以外，我們繼續預計 KEYTRUDA 的銷量增長強勁。然而，定價是一個越來越大的逆風，特別是當我們在主要歐洲市場推出新的適應症時，這將緩和美國以外的市場。生長。

Finally, we are confident in our ability to drive strong growth of GARDASIL, particularly in international markets. We are well positioned to protect many more people from HPV-related cancers now and over the long term. And given the strong global demand for the vaccine, we see an acceleration of growth for GARDASIL in the full year 2023 relative to 2022 but not quite at the same level of growth achieved this quarter.

最後，我們對推動 GARDASIL 強勁增長的能力充滿信心，尤其是在國際市場上。我們現在和長期都處於有利地位，可以保護更多人免受 HPV 相關癌症的侵害。鑑於全球對疫苗的強勁需求，我們預計 GARDASIL 的增長在 2023 年全年將比 2022 年加速，但與本季度的增長水平不盡相同。

Now shifting to capital allocation, where we remain committed to our priority following the announcement to acquire Prometheus. We will continue to prioritize investments in our business and growing pipeline to realize the value of the many near- and long-term opportunities we see. We remain committed to our dividend and plan to increase it over time. Business development remains a high priority and we maintained the ability within our strong investment-grade credit rating to pursue additional science-driven, value-enhancing transactions going forward. We will continue to execute a modest level of share repurchases this year.

現在轉向資本配置，在宣布收購普羅米修斯之後，我們仍然致力於我們的優先事項。我們將繼續優先投資於我們的業務和不斷增長的管道，以實現我們看到的許多近期和長期機會的價值。我們仍然致力於我們的股息，併計劃隨著時間的推移增加它。業務發展仍然是重中之重，我們在強大的投資級信用評級範圍內保持能力，以尋求更多科學驅動、增值的交易。今年我們將繼續執行適度的股票回購。

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

總而言之，在全球對我們的創新藥物和疫苗的需求推動下，我們對我們的業務前景仍然充滿信心。我們擁有強大的財務和運營實力，我們持續出色的執行力將使我們能夠在未來為患者和股東創造價值。

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

有了這個，我現在想把電話轉給迪恩。

Thank you, Caroline. Hello, everyone. Today, I will provide notable updates since the last earnings call, starting with our progress in cardiovascular disease, oncology, then infectious disease and subsequently, immunology with our recently announced acquisition of Prometheus.

謝謝你，卡羅琳。大家好。今天，我將提供自上次財報電話會議以來的重大更新，首先是我們在心血管疾病、腫瘤學、傳染病和隨後的免疫學方面取得的進展，以及我們最近宣布收購普羅米修斯。

As Rob mentioned earlier, at the American College of Cardiology in conjunction with the World Congress of Cardiology meeting in New Orleans, results from the Phase III STELLAR trial, evaluating sotatercept for pulmonary arterial hypertension as well as data from the Phase IIb trial for our oral PCSK9 inhibitor candidate, MK-0616 and in development for the treatment of hypercholesterolemia were presented. In the STELLAR study, sotatercept in combination with stable background therapy met its primary endpoint with a substantial improvement in 6-minute walk distance at 24 weeks compared to placebo in combination with background therapy. The trial also met 8 out of 9 secondary measures, including a compelling reduction in time to clinical worsening or death versus placebo. These findings were published simultaneously in the New England Journal of Medicine.

正如 Rob 之前提到的，在美國心髒病學會和新奧爾良世界心髒病學大會會議上，III 期 STELLAR 試驗的結果評估了 sotatercept 治療肺動脈高壓的效果，以及我們口服藥物的 IIb 期試驗數據介紹了用於治療高膽固醇血症的 PCSK9 候選抑製劑 MK-0616。在 STELLAR 研究中，與安慰劑聯合背景療法相比，sotatercept 聯合穩定背景療法達到了其主要終點，即在 24 週時 6 分鐘步行距離有了顯著改善。該試驗還滿足了 9 項次要指標中的 8 項，包括與安慰劑相比顯著縮短至臨床惡化或死亡的時間。這些發現同時發表在《新英格蘭醫學雜誌》上。

We are working diligently to submit filings from the STELLAR data to regulatory agencies. And at this time, anticipate filing in the U.S. in the third quarter of this year, followed by the EU. We are advancing the broad sotatercept program, including the HYPERION, ZENITH, SOTERIA and Phase II CADENCE trials which are actively recruiting. Also at the ACC meeting, detailed Phase IIb results for MK-0616 were presented showing a reduction of LDL-cholesterol levels from 41.2%, up to 60.9% versus placebo. Up to 90% of patients receiving MK-0616 at the highest dose study were able to reach their LDL-C goal.

我們正在努力將 STELLAR 數據的文件提交給監管機構。而此時，預計今年第三季度在美國提交申請，其次是歐盟。我們正在推進廣泛的 sotatercept 計劃，包括正在積極招募的 HYPERION、ZENITH、SOTERIA 和 II 期 CADENCE 試驗。同樣在 ACC 會議上，MK-0616 的詳細 IIb 期結果顯示，與安慰劑相比，低密度脂蛋白膽固醇水平從 41.2% 降低到 60.9%。在接受最高劑量研究的 MK-0616 的患者中，高達 90% 的患者能夠達到他們的 LDL-C 目標。

An oral PCSK9 inhibitor could provide the opportunity for broad global access. We are initiating multiple Phase III studies, including in secondary prevention intermediate to high-risk primary prevention and for patients with heterozygous familial hypercholesterolemia. In parallel, we will conduct a cardiovascular outcomes trial. We are making progress towards our goal of developing medicines that improve and extend the lives of patients with cardiovascular diseases and look forward to providing updates in the future.

口服 PCSK9 抑製劑可以為全球廣泛使用提供機會。我們正在啟動多項 III 期研究，包括二級預防、中高風險一級預防和雜合子家族性高膽固醇血症患者。同時，我們將進行一項心血管結局試驗。我們正在朝著開發改善和延長心血管疾病患者生命的藥物的目標取得進展，並期待在未來提供更新。

Turning to oncology. As I have mentioned previously, a key area of focus and execution has been the development of treatment for early stages of cancer where there remains significant unmet need. We announced FDA acceptance of our application for KEYTRUDA in combination with platinum doublet chemotherapy as neoadjuvant followed by adjuvant therapy in patients with resectable Stage 2, 3A and 3B non-small cell lung cancer based on the findings to date from the KEYNOTE-671 study. The agency has set a PDUFA action date of October 16 and detailed findings will be presented at ASCO in June. Together with the approval of KEYTRUDA in the adjuvant setting for certain patients with non-small cell lung cancer based on KEYNOTE-091, the KEYNOTE-671 study builds on the wealth of data we have generated, relevant additional ongoing studies include KEYNOTE-867 and KEYLYNK-012. The comprehensive development program underscores our commitment to an area where there is significant opportunity to improve patient outcomes. Importantly, it also reinforces the need for early detection through lung cancer screening.

轉向腫瘤學。正如我之前提到的，重點和執行的一個關鍵領域是開發癌症早期階段的治療方法，其中仍有大量未滿足的需求。我們宣布 FDA 接受我們的 KEYTRUDA 聯合鉑雙藥化療作為新輔助治療的申請，根據 KEYNOTE-671 研究的最新發現，對可切除的 2 期、3A 期和 3B 期非小細胞肺癌患者進行輔助治療。該機構已將 PDUFA 行動日期定為 10 月 16 日，詳細調查結果將於 6 月在 ASCO 上公佈。連同 KEYTRUDA 在基於 KEYNOTE-091 的某些非小細胞肺癌患者的輔助治療中的批准，KEYNOTE-671 研究建立在我們已經生成的大量數據的基礎上，相關的其他正在進行的研究包括 KEYNOTE-867 和KEYLYNK-012。全面的發展計劃強調了我們對一個有重大機會改善患者結果的領域的承諾。重要的是，它還強化了通過肺癌篩查進行早期發現的必要性。

At the American Association for Cancer Research Annual Meeting in collaboration with Moderna, we announced detailed results from KEYNOTE-942, a Phase IIb study evaluating KEYTRUDA in combination with V940, also known as mRNA-4157, an individualized neoantigen therapy for the adjuvant treatment of stage 3 and 4 melanoma in patients with high risk of disease occurrence following complete reception. These results are the first to demonstrate improvement of recurrence-free survival over adjuvant standard of care PD-1 blockade in resected high-risk melanoma and provide the first randomized evidence that an individualized neoantigen therapy has potential benefit. The FDA has granted this combination breakthrough therapy designation and the European Medicine Agency has awarded prime designation for high-risk Stage 3 and 4 melanoma following complete resection.

在與 Moderna 合作的美國癌症研究協會年會上，我們公佈了 KEYNOTE-942 的詳細結果，這是一項評估 KEYTRUDA 與 V940（也稱為 mRNA-4157）聯合治療的 IIb 期研究，V940 是一種個體化新抗原療法，用於輔助治療癌症完全接受後疾病發生風險高的 3 期和 4 期黑色素瘤患者。這些結果首次證明，在切除的高危黑色素瘤中，與輔助護理標準 PD-1 阻斷相比，無復發生存期有所改善，並提供了第一個隨機證據，表明個體化新抗原治療具有潛在益處。 FDA 已授予該組合突破性療法稱號，歐洲藥品管理局已授予完全切除後高危 3 期和 4 期黑色素瘤的主要稱號。

Merck and Moderna plant initiated Phase III study in adjuvant melanoma this year and rapidly expand additional tumor types including non-small cell lung cancer. Together with Astellas and Seagen, we announced the FDA's accelerated approval of KEYTRUDA in combination with enfortumab vedotin an antibody drug conjugate for the treatment of adults with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin containing chemotherapy. This accelerated approval followed priority review and is based on data from the KEYNOTE-869 trial. This is an important advancement as this is the first U.S. approval of a regimen combining an anti-PD-1 therapy with an antibody drug conjugate in these patients. The approval adds to the success of our foundational work evaluating KEYTRUDA in combination with chemotherapy and provides promising evidence for combining immunotherapy with tissue-targeted anticancer agents.

默克和 Moderna 工廠今年啟動了輔助黑色素瘤的 III 期研究，並迅速擴大了包括非小細胞肺癌在內的其他腫瘤類型。我們與 Astellas 和 Seagen 一起宣布 FDA 加速批准 KEYTRUDA 與 enfortumab vedotin 聯合使用，這是一種抗體藥物偶聯物，用於治療不適合接受含順鉑化療的局部晚期或轉移性尿路上皮癌成人。這種加速批准遵循優先審查，並基於 KEYNOTE-869試驗的數據。這是一項重要的進步，因為這是美國首次批准將抗 PD-1 療法與抗體藥物偶聯物結合用於這些患者的治療方案。該批准增加了我們評估 KEYTRUDA 與化學療法相結合的基礎工作的成功，並為將免疫療法與組織靶向抗癌藥物相結合提供了有希望的證據。

We are well positioned to build upon this work with a portfolio of next-generation antibody drug conjugate through our collaboration with Kelun-Biotech. Planning is underway for an expansive global clinical development program, and we look forward to initiating Phase III trials for MK-2870, our TROP2 targeting ADC as both monotherapy and in combination with KEYTRUDA. We also announced that the FDA has accepted our application for 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. This filing is based on results from the Phase III KEYNOTE-859 trial in which KEYTRUDA plus chemotherapy demonstrated a significant improvement in overall survival, reducing the risk of death by 22% compared to chemotherapy alone in these patients regardless of PD-L1 expression. The agency has set a PDUFA action date of December 16. This provides us the opportunity to expand upon our approval for patients with HER2-positive disease based on KEYNOTE-811.

通過與科倫生物的合作，我們有能力在這項工作的基礎上開發下一代抗體藥物偶聯物產品組合。一項廣泛的全球臨床開發計劃的規劃正在進行中，我們期待啟動 MK-2870 的 III 期試驗，我們的 TROP2 靶向 ADC 作為單一療法和與 KEYTRUDA 聯合使用。我們還宣布，FDA 已接受我們的 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的申請。該備案基於 III 期 KEYNOTE-859試驗的結果，在該試驗中，無論 PD-L1 表達如何，KEYTRUDA 聯合化療顯示總體生存率顯著提高，與單獨化療相比，這些患者的死亡風險降低了 22%。該機構已將 PDUFA 行動日期定為 12 月 16 日。這使我們有機會根據 KEYNOTE-811 擴大對 HER2 陽性疾病患者的批准。

We recently announced positive data from the Phase III NRG-GY018 trial, investigating KEYTRUDA in combination with chemotherapy for the first-line treatment of patients with stage 3 to 4 or recurrent endometrial carcinoma. This is an important advancement for women with endometrial cancer building on our approvals from KEYNOTE-146, 775 and 158.

我們最近公佈了 III 期 NRG-GY018 試驗的陽性數據，該試驗研究了 KEYTRUDA 聯合化療一線治療 3 至 4 期或複發性子宮內膜癌患者的情況。在我們獲得 KEYNOTE-146、775 和 158 批准的基礎上，這對患有子宮內膜癌的女性來說是一項重要進步。

Earlier this year, the American Cancer Society's 2023 Annual Report on cancer facts and trends noted that survival for uterine malignancies had not improved over the past 4 decades due to a lack of treatment advances. We continue our work to provide better treatment options in women's cancer.

今年早些時候，美國癌症協會關於癌症事實和趨勢的 2023 年年度報告指出，由於缺乏治療進展，子宮惡性腫瘤的存活率在過去 4 十年中沒有改善。我們將繼續努力為女性癌症提供更好的治療選擇。

And finally, the treatment of metastatic castrate-resistant prostate cancer remains a significant and growing unmet need and, therefore, an area of ongoing commitment. We have gained important insights to date from our trials evaluating KEYTRUDA and Lynparza, and are planning to initiate Phase III studies of MK-5684 a, novel oral nonsteroidal inhibitor of CYP-11A1 from our collaboration with Orion by the end of this year. Also with AstraZeneca, we look forward to the discussion regarding the PROpel study at the upcoming Oncologic Drugs Advisory Committee meeting. We are proud of the progress we are making and look forward to hosting an investor event at ASCO in Chicago. Please mark your calendars for the evening of Monday, June 5, where we will provide an update on our oncology strategy and development program.

最後，轉移性去勢抵抗性前列腺癌的治療仍然是一個重要且不斷增長的未滿足需求，因此，這是一個持續承諾的領域。迄今為止，我們從評估 KEYTRUDA 和 Lynparza 的試驗中獲得了重要的見解，併計劃在今年年底前啟動 MK-5684 a 的 III 期研究，這是我們與 Orion 合作的新型口服非甾體 CYP-11A1 抑製劑。我們還與阿斯利康一起期待在即將召開的腫瘤藥物諮詢委員會會議上就 PROpel 研究進行討論。我們為我們正在取得的進步感到自豪，並期待在芝加哥的 ASCO 舉辦投資者活動。請將您的日曆標記為 6 月 5 日星期一晚上，屆時我們將提供我們的腫瘤學戰略和發展計劃的最新信息。

Turning to the progress of our infectious disease program. We are now actively enrolling multiple new Phase III studies for once daily islatravir in combination with doravirine, and with Gilead have resumed the Phase II study of an oral once-weekly combination treatment regimen of islatravir and Gilead lenacapavir. We are committed to advancing the science to offer new treatment options for the treatment of HIV.

談談我們傳染病項目的進展。我們現在正在積極招募多項針對每日一次 islatravir 聯合多拉韋林的新 III 期研究，並且與 Gilead 一起恢復了每週一次口服 islatravir 和 Gilead lenacapavir 聯合治療方案的 II 期研究。我們致力於推動科學發展，為治療 HIV 提供新的治療選擇。

On LAGEVRIO, we continue to prioritize global access during surges of COVID-19 around the world including in Japan, with the Ministry of Health, Labor and Welfare recently granted full approval for the treatment of COVID-19. We are proceeding with the evaluation of LAGEVRIO for the treatment of other viral respiratory infections and will show more as studies readout.

在 LAGEVRIO 上，在包括日本在內的世界各地 COVID-19 激增期間，我們繼續優先考慮全球訪問，厚生勞動省最近批准了 COVID-19 的治療。我們正在進行 LAGEVRIO 治療其他病毒性呼吸道感染的評估，並將在研究結果中顯示更多。

Finally, to our recently announced acquisition of Prometheus. Prometheus offers a strong scientific pedigree with a candidate that has shown exciting potential in both ulcerative colitis and Crohn's disease. TNF-like 1A is a novel target, which provides the potential opportunity to transform standard of care in a disease area where current therapies are often inadequate and high unmet need remains. Prometheus anti-TL1A antibody, PRA023 is a potential first-in-class late-stage clinical candidate with a unique dual mechanism of action, including anti-inflammatory and anti-fibrotic properties. PRA023 Phase II results in both ulcerative colitis and Crohn's disease demonstrated strong efficacy.

最後，關於我們最近宣布的對 Prometheus 的收購。 Prometheus 擁有強大的科學譜系，其候選人在潰瘍性結腸炎和克羅恩病方面均顯示出令人興奮的潛力。 TNF 樣 1A 是一個新的靶點，它提供了潛在的機會來改變當前治療往往不足且仍有大量未滿足需求的疾病領域的護理標準。 Prometheus 抗 TL1A 抗體 PRA023 是一種潛在的 first-in-class 晚期臨床候選藥物，具有獨特的雙重作用機制，包括抗炎和抗纖維化特性。 PRA023 II 期結果在潰瘍性結腸炎和克羅恩病中均顯示出強大的療效。

Further, at interim analysis, the data in the biomarker-positive subpopulation suggested even greater efficacy with patients more likely to achieve clinical remission. By combining Prometheus, deep understanding of an inflammatory bowel disease and Merck's deep expertise in developing and implementing biomarkers. We hope to usher in a new era in immunology where patients are matched with the right therapy based on a precision medicine approach. Prometheus biobank of IBD specimens have yielded deep molecular insights that form the foundation for the discovery of PRA052, and we look forward to building on that knowledge to gain further insights, which will enable the identification and prioritization of additional targets.

此外，在中期分析中，生物標誌物陽性亞群的數據表明，對於更有可能實現臨床緩解的患者，療效甚至更高。通過結合普羅米修斯、對炎症性腸病的深刻理解和默克在開發和實施生物標誌物方面的深厚專業知識。我們希望開創免疫學的新時代，讓患者根據精準醫學方法獲得正確的治療。 IBD 標本的普羅米修斯生物庫已經產生了深刻的分子洞察力，這些洞察力構成了發現 PRA052 的基礎，我們期待在這些知識的基礎上獲得進一步的洞察力，這將能夠識別其他目標並確定其優先級。

In closing, we continue to make progress towards our goal of creating innovative medicines that will improve the outcomes for patients. And now I will turn the call back to Peter.

最後，我們繼續朝著創造創新藥物的目標取得進展，以改善患者的預後。現在我會把電話轉回給彼得。

Thank you, Dean. Michelle, we're ready for Q&A. I'd like to ask analysts to limit themselves to 1 question today. We'd like to complete the call by the top of the hour. Thank you.

謝謝你，院長。米歇爾，我們準備好進行問答了。我想請分析師今天將自己限制在 1 個問題上。我們希望在整點前完成通話。謝謝。

(Operator Instructions) Terence Flynn with Morgan Stanley.

（操作員說明）Terence Flynn 與摩根士丹利。

This is Robert (inaudible) on for Terence. You and your partner, Moderna are conducting a Phase I basket trial of the PCV. Can you elaborate on the design of the trial and if you have any of the data in-house at this point?

我是特倫斯的羅伯特（聽不清）。您和您的合作夥伴 Moderna 正在進行 PCV 的 I 期籃子試驗。您能否詳細說明試驗的設計以及您目前是否有任何內部數據？

Yes. Thank you. This is Dean. I probably want to just focus really on the Phase IIIs that we're advancing in melanoma and likely in others. There is a basket trial that's going through to look at the extent of the tumors that a joint sort of KEYTRUDA plus a personalized or individualized neoantigen therapy will work. I can just give you a general sense. We have a little bit of a road map as to where immune sensitive tumors are, and we would likely prioritize those in our basket trial.

是的。謝謝。這是迪恩。我可能只想真正關注我們在黑色素瘤和其他人中推進的 III 期。正在進行一項籃子試驗，以了解聯合使用 KEYTRUDA 和個性化或個體化新抗原療法的腫瘤範圍。我只能給你一個大概的感覺。我們有一些關於免疫敏感腫瘤在哪裡的路線圖，我們可能會在我們的籃子試驗中優先考慮那些。

Great. Thank you, next question, please.

偉大的。謝謝，請下一個問題。

Your next caller is Seamus Fernandez with Guggenheim.

下一位來電者是古根海姆的 Seamus Fernandez。

So my question is actually on the Kelun Bio opportunity. Dean, just hoping if you could update us, I believe, previously, it was stated that we may see some longer-term data later this year. Just hoping to see if that is still the case or if competitive dynamics have kind of changed that commitment? And maybe if you could just help us understand your enthusiasm for that particular product and where you feel it would be likely differentiated from other products in the category?

所以我的問題實際上是關於科倫生物的機會。院長，希望你能告訴我們最新情況，我相信，之前曾說過我們可能會在今年晚些時候看到一些長期數據。只是希望看看情況是否仍然如此，或者競爭動態是否改變了這種承諾？也許您可以幫助我們了解您對該特定產品的熱情，以及您認為它可能與該類別中的其他產品有何不同？

I'll just answer by the competitive dynamics make us more enthusiastic to push our programs harder and faster. We will be providing data from the data that we have in a series of cancers at ASCO on June 5. We'll have an investor, but it will also be in the ASCO, I believe, already accepted for our presentation there as well. So we're very interested in that. And we're also very interested in the fact that -- as we know, the first evidence of anti-PD-1 with an antibody drug conjugates and our collaboration with Seagen has shown good effect, and we postulate that, that may be a broader impact, not just with one ADC or one indication, but more broadly, through multiple antibody drug conjugates and therefore, our interest in advancing not just the TROP2 ADC but many other ADCs that we haven't provided data as of this point.

我只是通過競爭動態來回答，這讓我們更加熱情地推動我們的計劃更加努力和更快。我們將在 6 月 5 日提供我們在 ASCO 上的一系列癌症數據中的數據。我們將有一個投資者，但它也會在 ASCO 中，我相信，我們在那裡的演示文稿也已經被接受。所以我們對此非常感興趣。我們也非常感興趣的事實是——正如我們所知，抗 PD-1 與抗體藥物偶聯物的第一個證據以及我們與 Seagen 的合作已經顯示出良好的效果，我們假設，這可能是更廣泛的影響，不僅僅是一種 ADC 或一種適應症，而是更廣泛地，通過多種抗體藥物偶聯物，因此，我們不僅有興趣推進 TROP2 ADC，還有許多我們目前尚未提供數據的其他 ADC。

Okay. Next question, please.

好的。請下一個問題。

Luisa Hector from Berenberg.

來自貝倫貝格的路易莎赫克托。

I wondered if you could give us an update on KEYTRUDA. Your -- how it's looking in the adjuvant lung setting and relative positioning against your competitor and how any subcutaneous formulation might change that either from the competitor or you? And when might we have that Phase III data on your newer former of the subcutaneous?

我想知道您是否可以向我們介紹 KEYTRUDA 的最新情況。你的 - 它在輔助肺設置和相對於你的競爭對手的相對定位中看起來如何，以及任何皮下製劑如何改變競爭對手或你的情況？我們什麼時候可以得到關於您較新的皮下前者的 III 期數據？

Let me just grab the question about the early-stage lung. As we've talked, the earlier stages are really important. We've already seen it in triple-negative breast cancer. We've seen it in RCC. We've seen it in melanoma. And I think the aperture of being able to do it in the lung is going to be substantial. Again, for our KEYNOTE-671, which is the first perioperative trial to announce a statistically significant and clinically meaningful improvement in EFS and statistically significant improvement in pathologic complete response. Those will be presented in June as well. I would also emphasize that event-free survival and overall survival are the primary endpoints of our study, and most competitors do not have OS as a primary endpoint.

讓我抓住關於早期肺的問題。正如我們所說，早期階段非常重要。我們已經在三陰性乳腺癌中看到它。我們已經在 RCC 中看到了它。我們已經在黑色素瘤中看到了它。而且我認為能夠在肺部做到這一點的孔徑將是巨大的。同樣，對於我們的 KEYNOTE-671，這是第一個宣布 EFS 有統計學意義和臨床意義改善以及病理完全反應有統計學意義改善的圍手術期試驗。這些也將在 6 月展示。我還要強調的是，無事件生存期和總生存期是我們研究的主要終點，大多數競爭對手沒有將 OS 作為主要終點。

I would also emphasize that this is also in the setting where we have perioperative, but we also have adjuvant as well. So we provide a broad treatment choice in relationship to moving forward in the earlier stage. In all earlier stage, whether it be lung, triple-negative, RCC, melanoma, I think it will be increasingly important to provide innovation that allows patients to have "more normal" ability to stay on these treatments long term, there are different profiles than a metastatic patient. And so we believe that giving other routes of administration will be important. And we're advancing our subcu pembrolizumab, especially with hyaluronidase because that gives us an ability to do both a Q3 weeks and importantly, also allows us to do a Q6 weeks because that frequency, I think, will be very important for patients.

我還要強調的是，這也是在我們有圍手術期的情況下，但我們也有佐劑。因此，我們提供了一個廣泛的治療選擇，關係到早期的進展。在所有早期階段，無論是肺癌、三陰性、RCC、黑色素瘤，我認為提供創新讓患者俱有“更正常”的能力並長期接受這些治療將變得越來越重要，有不同的概況比轉移患者。因此，我們認為提供其他給藥途徑將很重要。我們正在推進我們的 subcu pembrolizumab，特別是透明質酸酶，因為這使我們能夠同時進行 Q3 週，重要的是，還允許我們進行 Q6 週，因為我認為這種頻率對患者非常重要。

And Luisa, I might just add from a commercial perspective, the early stage launch in lung with KEYNOTE-091 is off to a good start. We're actually seeing good uptake. As you know, the challenge here is that the overall screening rates are lower. So it's going to be a slower climb than what we saw, for instance, or we have been seeing with triple-negative breast cancer. But as we sit here today, the launch is going well. And as we look forward, and hopefully, once we -- with the potential approval of KEYNOTE-671, we'll be the only company that has both adjuvant and neoadjuvant offerings as well as, obviously, a leadership position in the metastatic setting.

而路易莎，我可能只是從商業角度補充說，KEYNOTE-091在肺部的早期啟動是一個良好的開端。我們實際上看到了很好的吸收。如您所知，這裡的挑戰是總體篩選率較低。因此，它的上升速度將比我們所看到的要慢，例如，或者我們在三陰性乳腺癌中所看到的。但是當我們今天坐在這裡時，發布進展順利。正如我們所期待的那樣，希望一旦我們——在 KEYNOTE-671 可能獲得批准的情況下，我們將成為唯一一家同時擁有輔助和新輔助產品的公司，並且顯然在轉移環境中處於領先地位。

So as we sit here today, we continue to see this as a meaningful opportunity and long term will continue to drive growth for us in lung. But obviously, we've got to get that going to do that in the adjuvant setting. From a metastatic perspective, we're continuing to hold our leadership position.

因此，當我們今天坐在這裡時，我們繼續將其視為一個有意義的機會，從長遠來看，這將繼續推動我們在肺部的發展。但顯然，我們必須在輔助環境中做到這一點。從轉移的角度來看，我們將繼續保持領先地位。

Great. Thank you, Luisa. Next question, please.

偉大的。謝謝你，路易莎。請下一個問題。

Chris Shibutani with Goldman Sachs.

Chris Shibutani 與高盛。

Great. For sotatercept, certainly, a broad scope of potential not just from the STELLAR results, but in earlier and later line, you have HYPERION and ZENITH. Can you remind us if there's potential for interim readouts and if so, potential what time line? And relatedly, what are you thinking about in terms of your overall sort of PH -- PAH strategy? You have assets now with Prometheus as well that have potential to be used in the systemic sclerosis ILD population. A lot of opportunity. If you can just help frame some strategic thinking?

偉大的。對於 sotatercept，當然，廣泛的潛力不僅來自 STELLAR 結果，而且在更早和更晚的系列中，你有 HYPERION 和 ZENITH。您能否提醒我們是否有可能進行臨時讀數？如果有，可能的時間線是什麼？與此相關的是，您對 PH - PAH 策略的整體類型有何看法？您現在擁有 Prometheus 的資產，這些資產有可能用於系統性硬化症 ILD 人群。很多機會。如果你能幫助構建一些戰略思維？

Yes. I would just focus on the pulmonary artery hypertension. I would kind of keep that a little bit distinct from other forms of lung disease, 1 is a primary vascular. The other 1 is, I could say, primary parenchyma. So I kind of separate diseases like IPF and interstitial lung disease from scleroderma as distinct from those like pulmonary artery hypertension. You're right. We believe that sotatercept will be important. We are pushing forward with that sotatercept with a STELLAR. We have ZENITH, HYPERION. There are interim analysis, but I don't actually want to sort of lay out, many of them are event-driven. The ZENITH, as you well know, is really in a more advanced situation and HYPERION is really trying to get it more in the front line.

是的。我只關注肺動脈高壓。我會保持它與其他形式的肺部疾病有點不同，1 是原發性血管疾病。我可以說，另一個 1 是初級薄壁組織。因此，我將 IPF 和間質性肺病等疾病與硬皮病區分開來，以區別於肺動脈高壓等疾病。你說得對。我們相信 sotatercept 將很重要。我們正在通過 STELLAR 推進 sotatercept。我們有 ZENITH、HYPERION。有中期分析，但我實際上不想進行佈局，其中許多是事件驅動的。如您所知，ZENITH 確實處於更先進的情況，而 HYPERION 確實正在努力使其更多地處於前線。

We also believe that it will potentially reshape how people think about the treatment of PAH largely people thought about vasodilation or dilation. I think this mechanism is active in signaling inhibitor with the mechanism that it has, which remodels, the tissue will reshape the field and in reshaping it, it will potentially reshape the dynamics of the vasodilatory pathways and that's why we're so excited with our inhaled sGC program, MK-5475 because we think that could be a very important combination agent with other vasodilatory mechanisms that are already approved as well as in combination with sotatercept.

我們還相信，它可能會重塑人們對 PAH 治療的看法，主要是人們對血管舒張或擴張的看法。我認為這種機制在信號抑製劑中很活躍，它具有重塑的機制，組織將重塑磁場，重塑它時，它可能會重塑血管舒張通路的動力學，這就是為什麼我們對我們的產品如此興奮吸入 sGC 程序 MK-5475，因為我們認為它可能是一種非常重要的聯合藥物，與其他已經批准的血管舒張機制以及與 sotatercept 聯合使用。

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

偉大的。謝謝你，克里斯。請下一個問題。

Chris Schott with JPMorgan.

摩根大通的克里斯肖特。

This is Hardik Parikh filling in for Chris Schott. Just 1 question on the BD front. So when you're thinking about the progress that you guys have had in internal pipeline and then now you have the Prometheus deal. Is there a priority or a bias when you consider business development from either early or later stage deals or from therapeutic areas, oncology, CV or maybe some emerging therapeutic areas in your portfolio?

我是 Hardik Parikh，代替 Chris Schott。 BD 方面只有 1 個問題。因此，當你考慮你們在內部管道方面取得的進展時，現在你有了 Prometheus 交易。當您考慮早期或後期交易或治療領域、腫瘤學、CV 或您投資組合中的一些新興治療領域的業務發展時，是否存在優先級或偏見？

Yes. No, I appreciate the question. So obviously, in our view of this is really unchanged despite what you've seen us do both recently and to the fact you made -- point you made, we're seeing good progress in our internal pipeline. It starts with asking the question, where do we see the most compelling science that we think we can use to make a difference for an unmet need and it has a strategic fit and where we see value aligned. And that's where we move. As we sit here today, we continue to believe there are opportunities for us to continue to do business development. We are very, I would say, pleased with the progress of the internal pipeline. And as you look about the therapeutic areas where we have been adding, obviously, areas where you continue to see great science happening in oncology. There's a lot of science in oncology, immunology and we've seen in cardiovascular.

是的。不，我很欣賞這個問題。所以很明顯，儘管你看到我們最近做了什麼，而且你提出的事實——你提出的觀點，我們看到我們的內部管道取得了良好的進展。首先要問這個問題，我們在哪裡看到我們認為可以用來改變未滿足需求的最引人注目的科學，它具有戰略契合性，以及我們在哪裡看到價值一致。這就是我們移動的地方。當我們今天坐在這裡時，我們仍然相信我們有機會繼續進行業務發展。我想說，我們對內部管道的進展非常滿意。當你看到我們一直在增加的治療領域時，很明顯，你會繼續看到腫瘤學中發生偉大科學的領域。腫瘤學、免疫學和我們在心血管方面看到了很多科學。

So what's been driving us to the therapeutic areas has been the scientific opportunity we've seen. And as we think about early versus late, it really will depend on the confidence the scientific team has and the particular opportunity. So we don't target one versus the other. Although I will tell you, we continue to not believe that going after commercialized assets just for the sake of revenue is not our strategy. We're focused on building the pipeline, both near and long term, and we do deals across the full spectrum. We talk about the acquisitions in the Phase II, Phase III area, but we don't talk a lot about the fact we're doing a lot from collaborations and other licensing deals in their early phase. So we really look at the total phase of development and always will be driven by the pipeline. If it brings with it a commercial opportunity, great, but it always will have to have a pipeline element for us to want to go there.

因此，推動我們進入治療領域的是我們所看到的科學機遇。當我們考慮早期與晚期時，這實際上取決於科學團隊的信心和特定的機會。所以我們不針對一個與另一個。雖然我會告訴你，但我們仍然不認為僅僅為了收入而追求商業化資產不是我們的戰略。我們專注於建立短期和長期的管道，我們在整個範圍內進行交易。我們談論了第二階段、第三階段領域的收購，但我們並沒有過多談論我們在早期階段的合作和其他許可交易中做了很多事情。所以我們真正關注開發的總階段，並且始終由管道驅動。如果它帶來商業機會，那很好，但它總是必須有一個管道元素讓我們想要去那裡。

Great, thank you. Next question, please.

太好了謝謝。請下一個問題。

Carter Gould with Barclays.

卡特古爾德與巴克萊銀行。

I guess for Rob and Caroline, would love to kind of hear your latest thoughts on sort of the EU proposed legislation and how that potentially changes how you think about launching drugs in Europe? And I guess also, I guess the read-through would be also to how potential business development as well? And as you think about the timing of the revenues and potentially shorter exclusivity periods? Any thoughts on that front would be helpful.

我想 Rob 和 Caroline 很想听聽你們對歐盟擬議立法的最新想法，以及這可能如何改變你們對在歐洲推出藥物的看法？而且我想，我想通讀也會對潛在的業務發展有多大影響？當你考慮收入的時間和可能更短的獨占期時？在這方面的任何想法都會有所幫助。

Yes. So if you look at what the EU just put out, obviously, the high-level message is overall on balance, we are concerned that it continues to put innovation at a disadvantage in Europe and puts Europe at a competitive disadvantage as we think about where to invest our dollars and where to bring new products. Now that said, on balance, there were elements of what were proposed that actually we support. There are elements that we think need to be changed. On the side of the support, clearly, the fact that they have made some efforts to simplify and modernize the regulatory framework, which has the potential to accelerate approvals. That was very much something the industry pushed for, and we feel good about. But as you point out, the area that balances that, that is very concerning is the fact that they have reduced the data exclusivity period and made it largely contingent upon you're launching in across the member states, whether or not you're doing comparative studies and whether or not you have launches.

是的。因此，如果你看一下歐盟剛剛發布的內容，顯然，高層信息總體上是平衡的，我們擔心它繼續使歐洲的創新處於劣勢，並使歐洲處於競爭劣勢，因為我們考慮在哪裡投資我們的美元以及在哪裡帶來新產品。話雖如此，總的來說，我們實際上支持提議的某些內容。我們認為有些元素需要改變。在支持方面，很明顯，他們已經做出了一些努力來簡化和現代化監管框架，這有可能加快審批速度。這是業界大力推動的事情，我們對此感到滿意。但正如你指出的那樣，平衡這一點的領域非常令人擔憂，因為他們已經縮短了數據獨占期，並使其在很大程度上取決於你是否在各個成員國推出，無論你是否正在做比較研究以及您是否有發布。

So we need to understand that. We're going to continue to try to make sure people understand the implications that can have as we think about where we would launch products, and that's work we will do. We have a couple of years probably before this is put in place. So we have time to do the negotiation. As I sit here today, I wouldn't say that I see specific implications to our business development strategy, it's more of just the general theme of what is a push against innovation that concerns us because Europe is an important market, getting access to our medicines to the people in the European Union is important. We want to be there. We just have to make sure it's sustainable from a business perspective.

所以我們需要明白這一點。我們將繼續努力確保人們理解我們考慮在哪裡推出產品時可能產生的影響，這就是我們將要做的工作。我們可能還有幾年的時間才能落實到位。所以我們有時間進行談判。當我今天坐在這裡時，我不會說我看到了對我們的業務發展戰略的具體影響，它更多的只是推動我們關注的創新的一般主題，因為歐洲是一個重要的市場，可以進入我們的市場藥品對歐盟人民來說很重要。我們想在那裡。我們只需要確保它從商業角度來看是可持續的。

Great. Thank you, Carter. Next question.

偉大的。謝謝你，卡特。下一個問題。

Tim Anderson with Wolfe Research.

沃爾夫研究公司的蒂姆安德森。

I have a question on GARDASIL in China. So the GFA contract from your Chinese distributor published a couple of months ago shows really big purchase orders consistently for the next few years and it kind of trails off and declines. And it's interpreted literally it could suggest there was kind of a bolus effect going on where growth isn't linear. It goes up for a while, then it contracts as you work through warehouse patients. Is that how we should think about the longer-term uptake of GARDASIL in that particular market that it might not be linear?

我有一個關於 GARDASIL 在中國的問題。因此，幾個月前您的中國經銷商發布的 GFA 合同顯示，未來幾年的採購訂單量非常大，而且逐漸減少。從字面上看，它可能表明在增長非線性的地方存在某種推注效應。它會上升一段時間，然後隨著你處理倉庫病人而收縮。我們應該如何考慮 GARDASIL 在那個特定市場的長期使用，它可能不是線性的？

Yes. Just -- so if you look at the GFA contract, it's important to understand that the levels put in that contract are minimums. And in fact, we have shown and our history has been that actually we have supplied well over the minimum. So I wouldn't interpret that as the literal forecast of the business in China because there's opportunities with the expanded age cohorts as we continue to drive penetration in what is still a large unmet population, there is opportunities to do better than what's in that contract. And if history isn't indicative of the future, we would expect to see that move forward. So I would not interpret that as implying a decline in GARDASIL in China over the coming years.

是的。只是 - 因此，如果您查看 GFA 合同，重要的是要了解合同中規定的水平是最低限度。事實上，我們已經證明並且我們的歷史一直是我們實際上已經提供了遠遠超過最低限度的供應。所以我不會將其解釋為對中國業務的字面預測，因為隨著我們繼續推動對仍然大量未滿足的人口的滲透，擴大年齡段存在機會，有機會做得比合同中的更好.如果歷史不能預示未來，我們希望看到它向前發展。所以我不會將其解釋為暗示未來幾年 GARDASIL 在中國的銷量會下降。

The only thing I would add is from a research perspective, we remain focused on studies in China to support gender-neutral vaccination, which could be a great opportunity to protect more lives and provide growth into the future.

我唯一要補充的是，從研究的角度來看，我們仍然專注於在中國進行的研究，以支持不分性別的疫苗接種，這可能是保護更多生命和促進未來增長的絕佳機會。

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

偉大的。謝謝你，蒂姆。請下一個問題。

Evan Seigerman with BMO Capital Markets.

BMO 資本市場的 Evan Seigerman。

This is (inaudible) on for Evan. We wanted to ask with the sotatercept Phase III data, the Prometheus deal and novel assets like the oral PCSK9. Does the team now think that this will be enough to grow through the KEYTRUDA LOE?

這是 Evan 的（聽不清）。我們想詢問 sotatercept III 期數據、普羅米修斯交易和口服 PCSK9 等新資產。團隊現在是否認為這足以通過 KEYTRUDA LOE 實現增長？

Yes. I'll take the question, (inaudible). Obviously, I would start by saying we feel very good about the progress we've made in a very short period of time. So if you look at the opportunity to be in a situation to have sustainable growth well into the next decade. We feel like we've made significant progress. Whether it's -- as you point out, the deal with Acceleron and then I would add the broad and strong internal pipeline we have in cardiovascular that as you know, we've indicated has 8 potential launches in the 24 to 28 time frame, which has the potential to generate more than $10 billion as we move into the mid-2030s.

是的。我來回答這個問題，（聽不清）。顯然，我首先要說的是，我們對在很短的時間內取得的進展感到非常滿意。因此，如果您有機會在下一個十年實現可持續增長。我們覺得我們已經取得了重大進展。無論是 - 正如你指出的那樣，與 Acceleron 的交易，然後我會添加我們在心血管方面擁有的廣泛而強大的內部管道，正如你所知，我們已經表明在 24 到 28 的時間框架內有 8 次潛在的發射，這隨著我們進入 2030 年代中期，它有可能產生超過 100 億美元的收入。

We talked about the fact from an oncology perspective. If you look at what we have from an ADC portfolio and a lot of the small molecules, we've brought in through business development, excluding anything from the individualized neoantigen therapy, formally what we used to call the personalized cancer vaccine with Moderna. So that's not even counted. We see greater than $10 billion of opportunity from those assets in that same time frame.

我們從腫瘤學的角度談了這個事實。如果你看看我們從 ADC 產品組合和許多小分子中獲得的東西，我們通過業務發展帶來了，不包括個性化新抗原療法的任何東西，正式我們過去稱之為 Moderna 的個性化癌症疫苗。所以這還不算。在同一時間段內，我們從這些資產中看到了超過 100 億美元的機會。

So as we sit here today, we've made a lot of progress. I don't want to predict to I think we're in a position to grow or not. We're not giving specific guidance. But I would say I feel, given the rate of progress we've made in such a short period of time and given the timetable we have and our resources going forward and the progress that Dean is driving with his team in our labs, I am no longer focusing on 2028. I am looking at how do we have sustainable growth well into the next decade.

所以當我們今天坐在這裡時，我們已經取得了很多進展。我不想預測我認為我們是否能夠成長。我們沒有給出具體的指導。但我想說，我覺得，考慮到我們在如此短的時間內取得的進展速度，考慮到我們的時間表和我們未來的資源，以及 Dean 和他的團隊在我們實驗室推動的進展，我是不再關注 2028 年。我正在研究如何在下一個十年實現可持續增長。

Great. Thank you. Next question, please.

偉大的。謝謝。請下一個問題。

Andrew Baum with Citi.

安德魯鮑姆與花旗。

Question for Dean. Could you talk to the planned cardiovascular outcome trial for your oral PCSK9 in particular, how you balance some of the historic data supporting the idea that (inaudible) trial treatment duration is closely tied to efficacy and the parenterals were probably dosed for too short a time suggesting that you need to have a longer trial versus, on the other hand, the impact of the IRA containing returns at least in the Medicare population in the U.S.?

院長的問題。您能否談談計劃中的口服 PCSK9 心血管結局試驗，您如何平衡一些支持以下觀點的歷史數據：（聽不清）試驗治療持續時間與療效密切相關，而腸胃外給藥的時間可能太短這表明您需要進行更長時間的試驗，而另一方面，IRA 的影響至少在美國的 Medicare 人口中包含回報？

Thank you very much for that question. First of all, I just want to emphasize that we're in active discussions with regulatory agencies in relationship to our program as we define the Phase III trial. So that will put out there. The second point I would just emphasize is there is an evolving view that I think the field is coming to grips with. It's not just that LDL is an excellent biomarker. It's not just that PCSK9 is an excellent pathway. It is the fact that our 0616 interdicts exactly in the same place as some of the antibodies how one interprets that and how one thinks about biomarker data in that setting, I think it will be an evolving discussion with the regulatory agencies.

非常感謝你提出這個問題。首先，我只想強調，在我們定義 III 期試驗時，我們正在與監管機構就我們的計劃進行積極討論。所以那會放在那裡。我要強調的第二點是，我認為該領域正在逐漸適應一種不斷發展的觀點。不僅僅是 LDL 是一種出色的生物標誌物。不僅僅是因為 PCSK9 是一個很好的途徑。事實上，我們的 0616 與一些抗體在同一個地方完全禁止人們如何解釋它以及人們如何看待這種情況下的生物標誌物數據，我認為這將是與監管機構的一個不斷發展的討論。

The second question that you point out is the historic in the previous. I think you're referring to the fact that there is a view that if those studies with the antibodies had gone out a little bit longer, that they would have had a more profound impact in terms of outcomes. Those are things that we are speaking to the regulatory agencies as they think about the difference between the biomarker and the outcomes trial. But I do -- I would echo your point of view, which is one doesn't want to go too short that one risks the full maximum impact that you can have on the label, but that, as you said, needs to be balanced with whatever the IRI looks like how many years from now. So those are the balances. But your observation about the other trials is one that we observed as well. And my general thinking is we should try to maximize the impact that we have on patients because whatever that label is, that label will stay forever.

你指出的第二個問題是之前的歷史性問題。我想你指的是這樣一個事實，即有一種觀點認為，如果這些抗體研究的時間延長一點，它們會對結果產生更深遠的影響。這些是我們在監管機構考慮生物標誌物和結果試驗之間的區別時正在與他們交談的事情。但我願意——我會贊同你的觀點，這是一個不想太短的人冒著你可以對標籤產生的最大影響的風險，但正如你所說，需要平衡無論 IRI 看起來像從現在起多少年後。所以這些就是餘額。但是你對其他試驗的觀察也是我們觀察到的。我的一般想法是，我們應該盡量擴大我們對患者的影響，因為無論標籤是什麼，標籤將永遠存在。

Thank you, Andrew. Next question, please.

謝謝你，安德魯。請下一個問題。

Mara Goldstein with Mizuho.

瑪拉戈爾茨坦與瑞穗。

I wanted to also ask a question on the personalized cancer vaccine with Moderna. Coming out of AACR, the response rate for the monotherapy arm, the KEYTRUDA arm seemed low relative to some of the sort of historical comparisons. And I'm wondering if you could speak to that, particularly in light of what we have seen for other therapeutics that are being tested against KEYTRUDA monotherapy comparators?

我還想問一個關於 Moderna 個性化癌症疫苗的問題。從 AACR 來看，單藥治療組的反應率，KEYTRUDA 組相對於某些歷史比較而言似乎較低。我想知道你是否可以談談這一點，特別是考慮到我們所看到的針對 KEYTRUDA 單一療法比較藥物進行測試的其他療法的情況？

Yes. So let me just state that it's always something that we do and everyone else does, which is this cross-trial comparison between companies, but also within companies and their own agent. What I will say is that some of the issues that have been discussed was the pembrolizumab monotherapy arm performed comparably to KEYNOTE-054 in the high-risk subgroups, which is 3C and D. and those were also included in the KEYNOTE-942. And in general, the KEYNOTE-942 had more advanced disease than those in KEYNOTE-054. So there is a way for us to sort of probabilitized given the same stage. So we're very comfortable with the pembrolizumab monotherapy arm in the trial that Merck and Moderna proceeded with.

是的。所以我只想說，這始終是我們和其他人所做的事情，這是公司之間的交叉試驗比較，也是公司內部和他們自己的代理人之間的交叉試驗比較。我要說的是，已經討論的一些問題是派姆單抗單藥治療組在高風險亞組（3C 和 D）中的表現與 KEYNOTE-054 相當，這些也包含在 KEYNOTE-942 中。總的來說，KEYNOTE-942 比 KEYNOTE-054 中的疾病更嚴重。因此，我們有一種方法可以在給定相同階段的情況下進行概率化。因此，在默克和 Moderna 進行的試驗中，我們對 pembrolizumab 單藥治療臂感到非常滿意。

I just want to just reemphasize that this to us is an important development scientifically. This is really the first time that I can recall seeing the impact of a personalized or individualized neoantigen therapy or a personalized cancer vaccine that has that profound of a readout in a Phase II. So we're excited to advance that to Phase III for melanoma and to spool up other trials in Phase III as we look to see how far we can push this strategy.

我只想再次強調，這對我們來說是一個重要的科學發展。這真的是我第一次看到個性化或個性化新抗原療法或個性化癌症疫苗的影響，這些疫苗在 II 期中具有如此深遠的讀數。因此，我們很高興將其推進到黑色素瘤的 III 期，並在 III 期進行其他試驗，因為我們希望看到我們可以將這一戰略推進多遠。

Thank you, Mara. Next question, please.

謝謝你，瑪拉。請下一個問題。

Umer Raffat with Evercore.

Evercore 的 Umer Rafat。

Dean, on TIGIT, we know the doublet arm was not going to meet the PFS. So by extension, the triplet may have a shot at meeting PFS. And my question is, what is your confidence in getting to at least a 20% benefit or so on PFS? And if that plays out, you just wait for Phase III? Do you speak to regulator? Like what happens next, considering the second line trial?

Dean，在 TIGIT 上，我們知道雙臂不會達到 PFS。因此，推而廣之，三胞胎可能有機會達到 PFS。我的問題是，您對在 PFS 上獲得至少 20% 左右的收益有多大信心？如果成功了，你就等第三階段？你跟監管機構說話嗎？接下來會發生什麼，考慮二線試驗？

So I would just emphasize that I think you're speaking about the Phase II trial. And those Phase II trials do provide us sort of views of how to think about the 5 Phase III trials that we have ongoing. I will just say that those 5 Phase III trials are going to be the thing that the FDA looks at. That's what they're going to look at and we're advancing those. And we're advancing them not just in metastatic situations. We have a series of them in lung. But I also just want to emphasize something that I've said previously. It relates to what people have said about KEYNOTE-671. It relates to the question about individualized neoantigen therapy, and it will relate here. When we think about IO strategies and especially IO plus IO strategies, increasingly, our eyes are turning into the earlier stages of diseases both because it's very important for patients. It's a time where we can really interdict early, but we also think that, that's an important place for us to relook on all of our assets that are IO-IO in that earlier stage.

所以我只想強調，我認為你在談論 II 期試驗。這些 II 期試驗確實為我們提供了一些關於如何思考我們正在進行的 5 項 III 期試驗的觀點。我只想說這 5 項 III 期試驗將成為 FDA 關注的內容。這就是他們要看的東西，我們正在推進這些。我們不僅在轉移情況下推進它們。我們在肺中有一系列。但我也只想強調我之前說過的話。它與人們對 KEYNOTE-671 的評價有關。涉及到個體化新抗原治療的問題，這裡會涉及到。當我們考慮 IO 策略，尤其是 IO 加 IO 策略時，我們的目光越來越多地轉向疾病的早期階段，因為這對患者來說非常重要。現在是我們真正可以儘早阻止的時候，但我們也認為，這是我們重新審視早期階段所有 IO-IO 資產的重要場所。

Thank you, Umer. Next question, please.

謝謝你，烏默爾。請下一個問題。

Daina Graybosch with SVB Securities.

SVB 證券公司的 Daina Graybosch。

Related to the previous 2 in your answer, Dean, in early-stage melanoma it looks like you're going to be pursuing 2 Phase III combinations in parallel, adding on your TIGIT vivo and adding on the individualized neoantigen therapy. I wonder if you could talk to why you're taking 2 large shot on goal in the same indication? And should we expect a similar strategy generally? And for these 2 add-ons specifically and other early-stage indications?

與你回答中的前 2 個相關，Dean，在早期黑色素瘤中，你似乎將同時進行 2 個 III 期組合，添加你的 TIGIT 體內並添加個體化新抗原療法。我想知道你是否可以談談為什麼在相同的指示下你要射門兩次？我們應該普遍期待類似的策略嗎？對於這 2 個附加組件和其他早期適應症？

Yes. So I would just step back for just a moment. Our ability to go into earlier-stage cancers were just unlocked maybe a couple of years ago, right? And in order to do combinations, it's very important that your base molecule actually has an impact because that allows you to do contributions of components. So we're very comfortable moving our IO-IO strategies in earlier stages. We are doing it, as you said, both for pembro and TIGIT and as well as pembro plus the individualized neoantigen therapy. We're very confident that the desire of patients to be there is substantial. And our ability to recruit and do an important trial there is also important.

是的。所以我會退後一步。我們進入早期癌症的能力可能在幾年前才剛剛解鎖，對吧？為了進行組合，你的基礎分子實際上有影響是非常重要的，因為這可以讓你做出組件的貢獻。所以我們很樂意在早期階段移動我們的 IO-IO 策略。正如您所說，我們正在為 pembro 和 TIGIT 以及 pembro 和個體化新抗原療法做這件事。我們非常有信心，患者對那裡的渴望是巨大的。我們在那裡招募和進行重要試驗的能力也很重要。

I would also say that as you see more readouts of earlier-stage cancer for any of our assets, whether it be Lynparza, whether it be an ADC or whether it be KEYTRUDA, it will be likely that we will target multiple combinations in those spaces.

我還要說的是，當你看到更多關於我們任何資產的早期癌症的讀數時，無論是 Lynparza、ADC 還是 KEYTRUDA，我們很可能會針對這些領域的多種組合.

Great. Thank you, Daina. We're going to try to get to 2 more questions, please.

偉大的。謝謝你，黛娜。請再回答 2 個問題。

Colin Bristow with UBS.

科林·布里斯托 (Colin Bristow) 與瑞銀集團。

This is (inaudible) on for Colin. Congrats on the quarter. So another question on KEYTRUDA. So how much of a protective strategy in terms of the exclusivity could the subcutaneous formulation of the KEYTRUDA would afford you?

這是（聽不清）Colin 的發言。祝賀這個季度。所以關於 KEYTRUDA 的另一個問題。那麼，就排他性而言，KEYTRUDA 的皮下製劑能為您提供多少保護策略？

Yes. So I appreciate the question. As we look at the subcutaneous formulation and where that can be utilized, obviously, it's focused more where we have monotherapy as we look at earlier lines of therapy. So as we continue to advance our adjuvant and new adjuvant strategy across multiple tumor types and then where we are combining KEYTRUDA with small molecules. Based on what we see, as we look out, we would expect about half of what we have as KEYTRUDA would be addressable through the subcutaneous route based on that definition of those areas.

是的。所以我很欣賞這個問題。當我們研究皮下製劑以及可以使用的地方時，顯然，當我們研究早期的治療方法時，它更側重於我們有單一療法的地方。因此，隨著我們繼續推進針對多種腫瘤類型的輔助和新輔助策略，然後我們將 KEYTRUDA 與小分子相結合。根據我們所看到的，正如我們所看到的，我們預計我們擁有的 KEYTRUDA 的大約一半將根據這些區域的定義通過皮下途徑進行尋址。

Great. Thank you. Final question, please.

偉大的。謝謝。最後一個問題，請。

Trung Huynh with Credit Suisse.

瑞士信貸的 Trung Huynh。

Just a quick one. Given your renewed interest in immunology, I just wanted to ask about gefapixant. GSK recently bought a product with a similar mechanism of action for around $2 billion. They had described peak sales in the single billion dollar range. So perhaps can you just give us an update of where gefapixant is post the CRL that you have? And what's your expectations for this opportunity?

只是一個快速的。鑑於您對免疫學重新產生興趣，我只想問問有關 gefapixant 的問題。 GSK 最近以大約 20 億美元的價格購買了一種具有類似作用機制的產品。他們描述了十億美元範圍內的最高銷售額。那麼，也許您能告訴我們 gefapixant 在哪裡發布您擁有的 CRL 的最新信息嗎？您對這個機會有何期望？

Yes, I'll start with that. So as you recall, gefapixant, we had positive Phase III trials. We had a CRL. The CRL has nothing to do with the safety or really any major concern that would require another clinical trial. The focus was on the way that the analysis was done and the way that costs were counted. We have submitted additional analysis and will be submitting additional analysis to the FDA in the first half of this 2023. In general, I believe that the timing is that on submission of all of that data, generally speaking, the FDA then readjusted CRL in -- within 6 months. We have it already approved in Japan and Switzerland. And as you said, there is a renewed interest given the recent transaction, and I don't know if Caroline, would you like to answer that?

是的，我會從那開始。所以你記得，gefapixant，我們進行了積極的 III 期試驗。我們有一個 CRL。 CRL 與安全性無關，也與需要另一項臨床試驗的任何重大問題無關。重點是分析的完成方式和成本的計算方式。我們已經提交了額外的分析，並將在 2023 年上半年向 FDA 提交額外的分析。總的來說，我認為時間是在提交所有這些數據後，一般來說，FDA 然後在 - - 6 個月內。我們已經在日本和瑞士獲得批准。正如你所說，鑑於最近的交易，人們重新產生了興趣，我不知道 Caroline，你願意回答這個問題嗎？

So I would just add that today, this is a population that is very underserved, 1 in 10 people here in the United States have chronic cost. So it's a market that will need to be built. But should we be successful with our work with the FDA, we look forward to bringing forward an option that will be beneficial to patients and will drive revenue for our company.

所以我只想補充一點，今天，這是一個服務非常不足的人群，在美國這裡，十分之一的人有慢性費用。所以這是一個需要建立的市場。但如果我們與 FDA 的合作取得成功，我們期待提出一個對患者有益並為我們公司增加收入的選擇。

Great. Thank you, Trung, and thank you all for your very good questions today. We look forward to hearing from you and engaging with you in the future. Thanks a lot.

偉大的。謝謝 Trung，也感謝大家今天提出的非常好的問題。我們期待著收到您的來信並在未來與您合作。多謝。

Thank you. This concludes today's conference call. You may go ahead and disconnect at this time.

謝謝。今天的電話會議到此結束。此時您可以繼續並斷開連接。