默克藥廠 (MRK) 2023 Q2 法說會逐字稿

Thank you for standing by. Welcome to the Merck & Co. Q2 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二季度銷售和收益電話會議。 （操作員說明）此通話正在錄音。如果您有任何異議，您可以此時斷開連接。

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

我現在想將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, Cedric, and good morning, everyone. Welcome to Merck's Second 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.

謝謝你，塞德里克，大家早上好。歡迎參加默克 2023 年第二季度電話會議。董事長兼首席執行官 Rob Davis 將在今天的電話會議上發表講話；卡羅琳·利奇菲爾德，首席財務官；以及默克研究實驗室總裁 Dean Li 博士。

Before we get started, I'd like to point out a few items. You will see that we have items in our GAAP results such as acquisition-related charges, restructuring costs and certain other items. You should note that we have excluded these from our non-GAAP results and provided reconciliation in our press release.

在開始之前，我想指出一些事項。您會看到我們的 GAAP 結果中有一些項目，例如收購相關費用、重組成本和某些其他項目。您應該注意到，我們已將這些數據排除在我們的非公認會計準則業績之外，並在我們的新聞稿中提供了調節表。

I would like to remind you that some of the statements that we make today may be considered forward-looking statements within the meaning of the safe harbor provision of the United States 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 1995 年美國私人證券訴訟改革法案安全港條款含義內的前瞻性聲明。此類聲明是根據當前的情況做出的。默克管理層的信念，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存在不確定性，實際結果可能與前瞻性陳述中提出的結果存在重大差異。

Our SEC filings, including Item 1A in the 2022 10-K, identify certain risk factors and cautionary statements that could cause the company's actual results to differ materially from those projected in any of our forward-looking statements made this morning. Merck undertakes no obligation to publicly update any forward-looking statements.

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

During today's call, a slide presentation will accompany our speakers' prepared remarks. These slides, along with 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，我們的演講者準備好的講話將附有幻燈片演示。這些幻燈片以及收益發布、今天準備的評論和我們向 SEC 提交的文件均發佈在默克網站的投資者關係部分。

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

有了這個，我想把電話轉給羅布。

Thanks, Peter. Good morning, and thank you for joining today's call. We continue to make great progress in bringing forward compelling science to help address the world's most urgent unmet medical needs. Thanks to the unwavering commitment and discipline of our global teams, we're advancing our innovative pipeline and executing operationally in support of our key growth drivers. Our science-led strategy is generating innovations that save and improve the lives of patients and animals around the world and is delivering strong underlying growth for our business.

謝謝，彼得。早上好，感謝您參加今天的電話會議。我們在提出令人信服的科學以幫助解決世界上最緊迫的未滿足的醫療需求方面繼續取得巨大進展。得益於我們全球團隊堅定不移的承諾和紀律，我們正在推進我們的創新渠道並執行運營以支持我們的關鍵增長動力。我們以科學為主導的戰略正在產生創新，拯救和改善世界各地患者和動物的生活，並為我們的業務帶來強勁的潛在增長。

We're building on our strong track record in advancing our strategic priorities. We're progressing our deep pipeline, including sotatercept, for which we have completed our FDA submission and augmenting it with further strategic business development where we can add value by applying our clinical expertise and leveraging our global scale to accelerate broad access to patients.

我們正在鞏固我們在推進戰略重點方面的良好記錄。我們正在推進我們的深層管道，包括 sotatercept，我們已經完成了 FDA 的提交，並通過進一步的戰略業務開發來增強它，我們可以通過應用我們的臨床專業知識和利用我們的全球規模來加速廣泛的患者獲得服務來增加價值。

An excellent example of this is our acquisition of Prometheus Biosciences, which we completed in June. We're now actively integrating the talented team and are moving with speed toward initiation of a Phase III clinical trial. The addition of Prometheus significantly strengthens our presence in immunology, an area with substantial unmet medical need, and builds on the significant scientific insight we have gained in immuno-oncology.

一個很好的例子是我們於 6 月份完成的對 Prometheus Biosciences 的收購。我們現在正在積極整合才華橫溢的團隊，並正在快速啟動 III 期臨床試驗。 Prometheus 的加入顯著增強了我們在免疫學這一醫療需求未得到滿足的領域的影響力，並建立在我們在免疫腫瘤學方面獲得的重要科學見解的基礎上。

It also brings us a potential first-in-class, best-in-class novel TL1A inhibitor, which provides us the opportunity to transform the standard of care in a patient population suffering from debilitating immune-mediated diseases. With the foundation of great science and the legacy of commercial excellence, we're well positioned to deliver sustainable value over the long term.

它還為我們帶來了一種潛在的一流、一流的新型 TL1A 抑製劑，使我們有機會改變患有免疫介導疾病的患者群體的護理標準。憑藉偉大的科學基礎和卓越的商業遺產，我們有能力長期提供可持續的價值。

Focusing now on the short term, we delivered strong underlying growth, excluding the year-over-year decline in LAGEVRIO sales, led by robust demand across key growth drivers in Oncology and Vaccines. We remain confident in our outlook for the remainder of 2023, which Caroline will address in just a moment.

現在著眼於短期，我們實現了強勁的基本增長，排除了 LAGEVRIO 銷售額同比下降的情況，這是由腫瘤學和疫苗領域主要增長驅動因素的強勁需求帶動的。我們對 2023 年剩餘時間的前景仍然充滿信心，卡羅琳稍後將談到這一點。

Moving to our research organization, our promising late-stage pipeline continues to demonstrate tangible and impactful benefits for patients across a broad range of diseases. In Oncology, we highlighted data from our expansive pipeline at ASCO, including for KEYTRUDA, in earlier-stage lung cancer.

轉向我們的研究組織，我們前景光明的後期產品線繼續向多種疾病的患者展示切實而有影響力的益處。在腫瘤學方面，我們重點介紹了 ASCO 廣泛管道中的數據，包括用於早期肺癌的 KEYTRUDA。

The strong results of KEYNOTE-671 for the neoadjuvant and adjuvant treatment of patients with non-small cell lung cancer support our aspiration to fundamentally shift the way cancer is managed by developing treatment regimens in the earlier-stage setting, where the potential for better outcomes is higher. Additionally, we're leveraging KEYTRUDA's wide-reaching benefit across a range of cancer types to identify and bring forward promising new candidates.

KEYNOTE-671 對非小細胞肺癌患者進行新輔助和輔助治療的強勁結果支持了我們通過開發早期治療方案從根本上改變癌症治療方式的願望，在早期階段有可能獲得更好的結果更高。此外，我們正在利用 KEYTRUDA 對多種癌症類型的廣泛益處來識別和推出有前途的新候選藥物。

At ASCO, we shared positive data for KEYTRUDA in combination with V940, our investigational individualized neoantigen therapy in collaboration with Moderna, in the adjuvant treatment of melanoma. And promising data was also presented by our partner, Kelun Biotech, for MK-2870, our TROP2-ADC, in non-small cell lung cancer. Each of these novel candidates offer a glimpse into the future of cancer care and the potential to meaningfully improve outcomes for patients.

在 ASCO 上，我們分享了 KEYTRUDA 與 V940 聯合治療的積極數據，V940 是我們與 Moderna 合作的研究性個體化新抗原療法，用於黑色素瘤的輔助治療。我們的合作夥伴科倫生物科技還提供了我們的 TROP2-ADC MK-2870 在非小細胞肺癌中的有希望的數據。這些新穎的候選藥物中的每一個都讓我們得以一睹癌症治療的未來以及有意義地改善患者治療結果的潛力。

We have also made progress outside of Oncology. We're advancing our population-specific approach to pneumococcal vaccination and are very pleased to have announced positive topline results for our adult vaccine candidate, V116. If approved, V116 would be the first pneumococcal conjugate vaccine specifically designed for adults.

我們在腫瘤學之外也取得了進展。我們正在推進針對特定人群的肺炎球菌疫苗接種方法，並且非常高興地宣布我們的成人候選疫苗 V116 取得了積極的頂線結果。如果獲得批准，V116 將成為第一種專為成人設計的肺炎球菌結合疫苗。

And Dean will speak to our progress in cardiometabolic disease including positive data we recently presented for our GLP-1/glucagon receptor dual agonist. I commend Dean and his team on the significant work being done to advance our broad pipeline and their commitment to Merck's purpose.

Dean 將講述我們在心臟代謝疾病方面的進展，包括我們最近提供的 GLP-1/胰高血糖素受體雙重激動劑的積極數據。我讚揚 Dean 和他的團隊為推進我們廣泛的產品線所做的重要工作以及他們對默克目標的承諾。

Innovation is the core of who Merck is, and it's what our company strives to achieve every day. We're grounded in the relentless pursuit of advancing science and raising the bar of innovation to deliver value for patients.

創新是默克的核心，也是我們公司每天努力實現的目標。我們堅持不懈地追求進步科學和提高創新標準，為患者創造價值。

With that in mind, I'd like to speak for a moment about the Inflation Reduction Act. We've consistently communicated our support for elements of the law that improve patient affordability and access, such as the Medicare Part D reform, but which do so without damaging the very promising long-term innovation potential of the biopharmaceutical industry.

考慮到這一點，我想談談《通貨膨脹削減法案》。我們一直表達了對提高患者負擔能力和獲取機會的法律要素的支持，例如醫療保險 D 部分改革，但這樣做不會損害生物製藥行業非常有前途的長期創新潛力。

Through the complaint we recently filed in U.S. District Court, Merck is taking a principled stand against the negative long-term impacts of the price negotiation provision of the IRA, which we believe amounts to unconstitutional price setting that violates several provisions of the U.S. Constitution. This misguided policy does not strike the right balance between incenting investment and innovation and improving affordability and access.

通過我們最近向美國地方法院提起的申訴，默克公司對 IRA 價格談判條款的負面長期影響採取了原則性立場，我們認為該條款構成違憲定價，違反了美國憲法的多項條款。這種誤導性的政策沒有在激勵投資和創新與提高負擔能力和獲取機會之間取得適當的平衡。

That said, we remain committed to working with the U.S. government to find a better approach to improve affordability and access while protecting further drug breakthroughs that benefit patients facing unmet medical needs. We know it is critical that we provide broad access both to our current portfolio of medicines and vaccines and to our future innovations in order to serve the greatest number of patients possible now and for years to come. Our upcoming annual impact report will highlight accomplishments across our 4 priority areas, including access to health, where a portion of employee compensation will now be driven by metrics linked to our progress.

儘管如此，我們仍然致力於與美國政府合作，尋找更好的方法來提高負擔能力和可及性，同時保護進一步的藥物突破，使面臨未滿足醫療需求的患者受益。我們知道，為了在現在和未來幾年為盡可能多的患者提供服務，我們必須為當前的藥物和疫苗組合以及未來的創新提供廣泛的獲取途徑，這一點至關重要。我們即將發布的年度影響報告將重點介紹我們在 4 個優先領域取得的成就，包括獲得健康，其中一部分員工薪酬現在將由與我們的進展相關的指標來驅動。

In summary, our science-led strategy is working. We're driving significant scientific, commercial and operational momentum, which we expect will enable strong full year growth. I want to thank our talented, dedicated and diverse global team for their hard work and commitment to delivering value for patients, shareholders and all of our stakeholders. With these efforts, I'm confident we will continue to drive sustained success well into the future.

總而言之，我們以科學為主導的戰略正在發揮作用。我們正在推動重大的科學、商業和運營勢頭，我們預計這將實現強勁的全年增長。我要感謝我們才華橫溢、敬業且多元化的全球團隊的辛勤工作和致力於為患者、股東和所有利益相關者創造價值的承諾。通過這些努力，我相信我們將在未來繼續取得持續成功。

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

這樣，我就把電話轉給卡羅琳。

Thank you, Rob. Good morning. As Rob noted, we delivered another very strong quarter with underlying growth driven by demand across our innovative portfolio. These results reflect the profound impact of our medicines and vaccines globally and reinforce the confidence we have in the health of our business and in the outlook for continued strong underlying growth.

謝謝你，羅布。早上好。正如羅布指出的那樣，我們又實現了一個非常強勁的季度，其基礎增長是由我們的創新產品組合的需求推動的。這些結果反映了我們的藥品和疫苗在全球範圍內的深遠影響，並增強了我們對業務健康發展和持續強勁增長前景的信心。

Now turning to our second quarter results. Total company revenues were $15 billion. Excluding the impacts from LAGEVRIO and foreign exchange, the business delivered very strong growth of 14%. The remainder of my revenue comments will be on an ex-exchange basis. Our Human Health business sustained its strong momentum. Excluding LAGEVRIO, growth was 17%, driven by Oncology and Vaccines. Sales in our Animal Health business increased 2% across both companion animal and livestock products.

現在轉向我們的第二季度業績。公司總收入為 150 億美元。排除LAGEVRIO和外彙的影響，該業務實現了14%的強勁增長。我的其餘收入評論將基於交換基礎上。我們的人類健康業務保持強勁勢頭。不包括 LAGEVRIO，在腫瘤學和疫苗的推動下，增長了 17%。我們的動物保健業務中伴侶動物和牲畜產品的銷售額均增長了 2%。

Now turning to the second quarter performance of our key brands. In Oncology, KEYTRUDA grew 21% to $6.3 billion, driven by increased utilization from approvals in earlier-stage cancers and continued strong global demand for metastatic indications. In the U.S., KEYTRUDA grew across all key tumor types and continues to benefit from usage in earlier-stage cancers, including triple-negative breast cancer as well as in certain types of renal cell carcinoma and melanoma. We are encouraged by the positive feedback from health care providers and initial uptake of KEYNOTE-091, reflecting the significant impact KEYTRUDA is having on patients with earlier-stage non-small cell lung cancer.

現在轉向我們主要品牌的第二季度業績。在腫瘤學領域，由於早期癌症批准的利用率增加以及全球對轉移適應症的持續強勁需求，KEYTRUDA 增長了 21%，達到 63 億美元。在美國，KEYTRUDA 在所有關鍵腫瘤類型中都有增長，並繼續受益於早期癌症的使用，包括三陰性乳腺癌以及某些類型的腎細胞癌和黑色素瘤。我們對醫療保健提供者的積極反饋和 KEYNOTE-091 的初步使用感到鼓舞，這反映了 KEYTRUDA 對早期非小細胞肺癌患者的重大影響。

Outside the U.S., KEYTRUDA is maintaining its leadership in non-small cell lung cancer. Growth was driven by demand in metastatic renal cell carcinoma and certain types of head and neck cancer as well as in earlier-stage cancers, including high-risk, early-stage triple-negative breast cancer and renal cell carcinoma, which saw continued uptake in recently launched markets.

在美國以外，KEYTRUDA 在非小細胞肺癌領域保持著領先地位。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（包括高風險、早期三陰性乳腺癌和腎細胞癌）的需求推動的，這些癌症在最近推出的市場。

Lynparza remains the market-leading PARP inhibitor. Alliance revenue grew 15%, driven by increased demand in certain international markets. Lenvima alliance revenue grew 6% due to increased demand for the treatment of certain patients with advanced renal cell carcinoma and endometrial cancer in the U.S., partially offset by lower sales in China.

Lynparza 仍然是市場領先的 PARP 抑製劑。受某些國際市場需求增長的推動，聯盟收入增長了 15%。由於美國某些晚期腎細胞癌和子宮內膜癌患者的治療需求增加，Lenvima 聯盟收入增長了 6%，但部分被中國銷售額下降所抵消。

Our Vaccines portfolio delivered exceptional growth led by GARDASIL, which grew 53% to $2.5 billion. Performance was driven by strong global demand, especially in China, where we are benefiting from the expanded indication of GARDASIL 9 for girls and women 9 to 45 years of age. Vaccine sales also benefited from increased uptake of VAXNEUVANCE following the ongoing pediatric launch, particularly in the U.S.

我們的疫苗產品組合在 GARDASIL 的帶動下取得了非凡的增長，增長了 53%，達到 25 億美元。強勁的全球需求推動了業績增長，尤其是在中國，我們受益於 GARDASIL 9 適應症擴大到 9 至 45 歲女孩和女性的情況。隨著兒科產品的持續推出，VAXNEUVANCE 的使用量增加也使疫苗銷售受益，尤其是在美國。

In our Hospital Acute Care portfolio, BRIDION sales grew 19%, driven by increased market share among neuromuscular blockade reversal agents in the U.S. Sales in our Animal Health business grew 2%. Livestock sales growth reflects price actions as well as higher demand for swine and poultry products, partially offset by lower demand for ruminant products, due in part to reduced herd sizes. Companion animal growth reflects price actions, including for the BRAVECTO line of products, partially offset by supply challenges for certain vaccines.

在我們的醫院急性護理產品組合中，由於美國神經肌肉阻滯逆轉劑市場份額增加，BRIDION 銷售額增長了 19%。我們的動物保健業務銷售額增長了 2%。牲畜銷售增長反映了價格走勢以及對豬和家禽產品的需求增加，但部分被反芻動物產品需求的下降所抵消，部分原因是畜群規模減少。伴侶動物的增長反映了價格走勢，包括 BRAVECTO 系列產品的價格走勢，但部分被某些疫苗的供應挑戰所抵消。

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 76.6%, an increase of 1.9 percentage points due to favorable product mix, including a benefit from the lower sales of LAGEVRIO. Operating expenses increased to $15.9 billion, including a $10.2 billion onetime charge related to the acquisition of Prometheus. Excluding this charge, operating expenses grew 10%. This growth reflects increased investments in support of near-term opportunities for our in-line portfolio and disciplined investments for the future as we advance our exciting early- and late-phase pipelines.

現在我將向您介紹我們損益表的其餘部分，我的評論將基於非公認會計原則。毛利率為 76.6%，增長 1.9 個百分點，得益於有利的產品組合，其中包括 LAGEVRIO 銷量下降的收益。運營支出增加至 159 億美元，其中包括與收購 Prometheus 相關的 102 億美元一次性費用。扣除此項費用，運營費用增長了 10%。這種增長反映了隨著我們推進令人興奮的早期和後期管道，為支持我們的內線投資組合的近期機會和未來的嚴格投資而增加的投資。

Other income was $19 million. Our tax provision was approximately $800 million. As a result of the Prometheus onetime charge, we had a pretax loss this quarter. This onetime charge is not tax deductible. Our tax rate is therefore a negative 18.4%. Taken together, we reported a loss of $2.06 per share, which includes a negative impact of $4.02 per share from the onetime charge related to the Prometheus transaction.

其他收入為 1900 萬美元。我們的稅收撥備約為 8 億美元。由於普羅米修斯一次性費用，我們本季度出現稅前虧損。這筆一次性費用不可免稅。因此，我們的稅率為負 18.4%。總的來說，我們報告每股虧損 2.06 美元，其中包括與 Prometheus 交易相關的一次性費用帶來的每股 4.02 美元的負面影響。

Turning now to our 2023 non-GAAP guidance. The underlying strength of our business has enabled us to raise and narrow our full year revenue guidance. We now expect revenue to be between $58.6 billion and $59.6 billion, an increase of $800 million at the midpoint.

現在轉向我們的 2023 年非 GAAP 指導。我們業務的潛在實力使我們能夠提高和縮小全年收入指導。我們現在預計收入將在 586 億美元至 596 億美元之間，中間增加 8 億美元。

This range reflects strong underlying year-over-year revenue growth of 10% to 11%, offset by the expected lower sales of LAGEVRIO, which we continue to estimate to be approximately $1 billion this year, and an approximate 2 percentage point negative impact from foreign exchange using mid-July rates. Our gross margin assumption is unchanged at approximately 77%.

這一範圍反映了 10% 至 11% 的強勁潛在同比收入增長，但被 LAGEVRIO 的預期銷售額下降所抵消（我們仍然估計今年約為 10 億美元），以及大約 2 個百分點的負面影響外匯使用七月中旬匯率。我們的毛利率假設保持在 77% 左右不變。

We now estimate operating expenses to be between $34 billion and $34.6 billion. This range includes $11.6 billion of acquisition and upfront collaboration, research and development expenses associated with Prometheus, Imago and Kelun. Our guidance does not assume additional significant potential business development transactions. We now assume other expense of approximately $100 million, which includes incremental financing costs related to Prometheus.

我們現在估計運營費用在 340 億美元至 346 億美元之間。該範圍包括與 Prometheus、Imago 和 Kelun 相關的 116 億美元收購和前期合作、研發費用。我們的指導不假設額外的重大潛在業務開發交易。我們現在假設其他費用約為 1 億美元，其中包括與 Prometheus 相關的增量融資成本。

Our full year tax rate is expected to be between 30.5% and 31.5%, reflecting an increase due to the Prometheus transaction of approximately 15 percentage points. We continue to assume approximately 2.55 billion shares outstanding. Taken together, we expect EPS of $2.95 to $3.05, which includes the onetime charge for Prometheus and a negative impact from foreign exchange of approximately 5 percentage points versus 2022 using mid-July rates.

我們的全年稅率預計在 30.5% 至 31.5% 之間，反映出 Prometheus 交易帶來的約 15 個百分點的增長。我們繼續假設流通股數量約為 25.5 億股。總而言之，我們預計每股收益為 2.95 美元至 3.05 美元，其中包括 Prometheus 的一次性費用以及外匯帶來的負面影響，與 2022 年（按 7 月中旬匯率計算）相比約 5 個百分點。

Recall, our prior guidance range was $6.88 to $7, which we noted at the time excluded Prometheus. Had we included the $4.02 onetime charge and an estimated $0.14 to advance the assets and financing costs, our prior guidance range would have been $2.72 to $2.84 with a midpoint of $2.78. Our current guidance midpoint of $3 represents an increase resulting from the strength in our business of approximately $0.24, partially offset by an incremental headwind from foreign exchange of approximately $0.02.

回想一下，我們之前的指導範圍是 6.88 美元至 7 美元，我們當時指出不包括 Prometheus。如果我們包括 4.02 美元的一次性費用和預計的 0.14 美元預支資產和融資成本，我們之前的指導範圍將為 2.72 美元至 2.84 美元，中間值為 2.78 美元。我們目前的指導中點為 3 美元，這表示我們的業務實力增加了約 0.24 美元，但部分被外匯帶來的約 0.02 美元的增量阻力所抵消。

Our guidance reflects our continued confidence in the strength of our business, driven by our key pillars, enabling us to deliver robust underlying growth while investing in our promising pipeline. As you consider your models, there are a couple of items to keep in mind.

我們的指導反映了我們對我們業務實力的持續信心，在我們的關鍵支柱的推動下，使我們能夠實現強勁的基礎增長，同時投資於我們有前途的產品線。當您考慮模型時，需要記住一些事項。

KEYTRUDA growth has been exceptional in recent quarters, outperforming our expectations, driven in part by robust uptake of recently launched earlier-stage indications. We continue to expect strong year-over-year growth of KEYTRUDA, but not quite at the levels experienced in recent quarters, as a result of lapping launches and the impact of continued pricing headwinds, particularly as we launch new indications in key European markets.

近幾個季度 KEYTRUDA 的增長非常出色，超出了我們的預期，部分原因是最近推出的早期適應症的強勁採用。我們仍然預計 KEYTRUDA 將實現強勁的同比增長，但由於上市時間滯後和持續的定價逆風的影響，特別是當我們在主要歐洲市場推出新適應症時，其增長幅度不會達到最近幾個季度的水平。

In addition, there was a small benefit from wholesaler purchase timing in the U.S. in the second quarter, which we expect to reverse in the third quarter. As we look out to 2024 and beyond, we continue to expect strong growth, including the impact of additional approvals. And as a reminder, while we expect the pace of growth of GARDASIL to be higher in 2023 than 2022, the rate of second half growth is anticipated to be below the first half, due in part to the timing of shipments to China.

此外，第二季度美國批發商的採購時機也帶來了一些小好處，我們預計這種情況將在第三季度扭轉。展望 2024 年及以後，我們繼續預計強勁增長，包括額外批准的影響。提醒一下，雖然我們預計 2023 年 GARDASIL 的增長速度將高於 2022 年，但下半年的增長速度預計將低於上半年，部分原因是向中國發貨的時間安排。

Now turning to capital allocation. We will continue to prioritize investments in our business and growing pipeline to drive near and long-term growth across our portfolio. We remain committed to our dividend with the goal of increasing it over time. Business development remains a priority. We remain well positioned to pursue the most compelling external science through value-enhancing business development to augment our pipeline. We continue to expect to execute a modest level of share repurchases this year.

現在轉向資本配置。我們將繼續優先考慮對我們的業務和不斷增長的管道的投資，以推動我們投資組合的近期和長期增長。我們仍然致力於派發股息，目標是隨著時間的推移不斷增加股息。業務發展仍然是首要任務。我們仍然處於有利地位，可以通過增值業務開發來追求最引人注目的外部科學，以擴大我們的產品線。我們仍然預計今年將進行適度的股票回購。

To conclude, as we enter the second half of the year, we remain very confident in both the strength of our underlying business, driven by global demand for our innovative medicines and vaccines and the excellent execution of our dedicated teams across all areas of our business, which will enable us to continue to deliver value to patients, customers and shareholders now and well into the future.

總而言之，隨著我們進入下半年，我們對我們的基礎業務實力仍然充滿信心，這得益於全球對我們創新藥物和疫苗的需求，以及我們各個業務領域的專業團隊的出色執行力。 ，這將使我們能夠在現在和未來繼續為患者、客戶和股東創造價值。

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. Good morning, everyone. It's my pleasure to provide an overview of the significant pipeline progress across multiple therapeutic areas since the first quarter call. Today, I will start with oncology, followed by vaccines and infectious diseases, and finally, on to our broader pipeline.

謝謝你，卡羅琳。大家，早安。我很高興概述自第一季度電話會議以來多個治療領域的重大管道進展。今天，我將從腫瘤學開始，然後是疫苗和傳染病，最後是我們更廣泛的產品線。

Starting with oncology. The development of meaningful treatment options for patients with earlier-stage disease, where there is greater prospect to improve outcomes, continues to be an area of significant progress. Last week, we announced the Phase III KEYNOTE-756 trial, evaluating KEYTRUDA in combination with chemotherapy in patients with high-risk, early-stage estrogen receptor-positive, HR-positive (sic) [ER-positive], HER2-negative breast cancer, met one of its dual primary endpoints of pathological complete response following the neoadjuvant part of the neoadjuvant/adjuvant study. This is the first Phase III study to demonstrate a positive result for an immunotherapy-based regimen in early-stage breast cancer for this patient population.

從腫瘤學開始。為早期疾病患者開發有意義的治療方案，改善預後的前景更大，仍然是一個取得重大進展的領域。上週，我們宣布了 III 期 KEYNOTE-756 試驗，評估 KEYTRUDA 聯合化療治療高危、早期雌激素受體陽性、HR 陽性（原文如此）[ER 陽性]、HER2 陰性乳腺患者癌症，在新輔助/輔助研究的新輔助部分之後達到了病理完全緩解的雙重主要終點之一。這是第一項 III 期研究，證明基於免疫治療的方案在早期乳腺癌患者群體中取得了積極的結果。

Further, in women's cancer and building on our progress in earlier stages of disease, we announced that the Phase III KEYNOTE A-18 trial met one of its primary endpoints of progression-free survival for treatment of newly diagnosed patients with high-risk locally advanced cervical cancer. This is the first study of KEYTRUDA plus chemoradiotherapy or radiotherapy to show statistically significant and clinically meaningful improvement in progression-free survival.

此外，在女性癌症領域，基於我們在疾病早期階段取得的進展，我們宣布 III 期 KEYNOTE A-18 試驗達到了治療新診斷的高危局部晚期患者的無進展生存期的主要終點之一宮頸癌。這是 KEYTRUDA 聯合放化療或放療的第一項研究，顯示無進展生存期具有統計學意義和臨床意義的改善。

At ASCO, as part of our investor event, we provided an overview of our clinical development pipeline and highlighted relevant data presentations. We have strong momentum as we evaluate the opportunity for KEYTRUDA in earlier stages of disease. Detailed results were presented from the ongoing KEYNOTE-671 study, evaluating KEYTRUDA in combination with platinum doublet chemotherapy as neoadjuvant therapy, followed by adjuvant KEYTRUDA in patients with resectable stage 2, 3a and 3b non-small cell lung cancer.

在 ASCO 上，作為投資者活動的一部分，我們概述了我們的臨床開發流程，並重點介紹了相關數據。當我們評估 KEYTRUDA 在疾病早期階段的機會時，我們擁有強勁的動力。正在進行的 KEYNOTE-671 研究提供了詳細結果，該研究評估了 KEYTRUDA 聯合鉑類雙藥化療作為新輔助治療，然後在可切除的 2、3a 和 3b 期非小細胞肺癌患者中使用輔助 KEYTRUDA。

Treatment with KEYTRUDA and chemotherapy before surgery followed by KEYTRUDA monotherapy after surgery reduced the risk of disease recurrence, progression or death by 42% versus preoperative chemotherapy alone. Subgroup analysis showed a consistent response, regardless of PD-L1 expression, histology and stage of disease. The PDUFA target action date is October 16.

與術前單獨化療相比，術前使用 KEYTRUDA 聯合化療治療，然後在術後使用 KEYTRUDA 單藥治療可將疾病復發、進展或死亡的風險降低 42%。亞組分析顯示出一致的反應，無論 PD-L1 表達、組織學和疾病階段如何。 PDUFA 的目標行動日期是 10 月 16 日。

With the approval of KEYNOTE-091 as treatment after surgery and adjuvant chemotherapy, along with the potential approval for KEYNOTE-671 as treatment before and after surgery, KEYTRUDA will provide the optionality to benefit more patients with earlier-stage non-small cell lung cancer.

隨著 KEYNOTE-091 獲批用於手術後和輔助化療的治療，以及 KEYNOTE-671 可能獲批用於手術前後的治療，KEYTRUDA 將為更多早期非小細胞肺癌患者提供選擇。 。

Further data were also presented for KEYNOTE-942 from our Phase IIb study of KEYTRUDA in combination with V940, an investigational individualized neoantigen therapy in collaboration with Moderna. The study showed a 65% reduction in risk of distant metastasis or death in patients with resected stage 3 and 4 melanoma compared to KEYTRUDA alone. We are eager to build upon these findings and have started enrolling patients into the registrational Phase III trial for adjuvant treatment of high-risk stage 2b to 4 melanoma, with plans to expand the program to additional tumor types, including non-small cell lung cancer.

我們還提供了 KEYTRUDA 與 V940 聯合的 KEYNOTE-942 IIb 期研究的進一步數據，V940 是與 Moderna 合作的一種研究性個體化新抗原療法。該研究顯示，與單獨使用 KEYTRUDA 相比，切除 3 期和 4 期黑色素瘤的患者的遠處轉移或死亡風險降低了 65%。我們渴望以這些發現為基礎，並已開始招募患者參加用於高風險 2b 至 4 期黑色素瘤輔助治療的註冊 III 期試驗，併計劃將該計劃擴展到其他腫瘤類型，包括非小細胞肺癌。

Finally, data presented for MK-2870, our investigational anti-TROP2 antibody-drug conjugate licensed from Kelun Biotech, showed encouraging antitumor activity in patients with relapsed or refractory locally advanced or metastatic non-small cell lung cancer, regardless of TROP2 expression level. We are advancing a broad clinical development program for this candidate, with global Phase III trials scheduled in lung cancer and additional tumor types.

最後，MK-2870（我們從科倫生物技術公司獲得許可的研究性抗 TROP2 抗體藥物偶聯物）提供的數據顯示，無論 TROP2 表達水平如何，對複發或難治性局部晚期或轉移性非小細胞肺癌患者都具有令人鼓舞的抗腫瘤活性。我們正在推進該候選藥物的廣泛臨床開發計劃，計劃針對肺癌和其他腫瘤類型進行全球 III 期試驗。

On the regulatory front, Lynparza, in combination with abiraterone and prednisone, was approved by the FDA for the treatment of adult patients with BRCA-mutated metastatic castration-resistant prostate cancer, an important area of unmet need. In addition, our supplemental biologics license application for KEYTRUDA, in combination with chemotherapy for patients with locally advanced unresectable or metastatic biliary tract cancer, based on findings from KEYNOTE-966, was accepted by the FDA for review. The PDUFA target action date is February 7, 2024.

在監管方面，Lynparza 與阿比特龍和潑尼松聯合治療，被 FDA 批准用於治療患有 BRCA 突變的轉移性去勢抵抗性前列腺癌的成年患者，這是一個未滿足需求的重要領域。此外，基於 KEYNOTE-966 的研究結果，我們針對 KEYTRUDA 聯合化療治療局部晚期不可切除或轉移性膽道癌患者的補充生物製劑許可申請已被 FDA 接受進行審查。 PDUFA 的目標行動日期是 2024 年 2 月 7 日。

We also announced new data from KEYNOTE-811, which demonstrated KEYTRUDA, in combination with trastuzumab and chemotherapy, showed a significant improvement in progression-free survival for the first-line treatment of HER2-positive advanced gastric or gastroesophageal junction adenocarcinoma in patients whose tumors were PD-L1 positive. Merck has discussed these findings with the FDA and is working to update the current indication for KEYTRUDA. In addition, based on the data from KEYNOTE-811 study, we received a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use.

我們還公佈了 KEYNOTE-811 的新數據，該數據表明 KEYTRUDA 與曲妥珠單抗和化療相結合，一線治療 HER2 陽性晚期胃或胃食管交界腺癌患者的無進展生存期顯著改善。 PD-L1 呈陽性。默克已與 FDA 討論了這些發現，並正在努力更新 KEYTRUDA 的當前適應症。此外，根據KEYNOTE-811研究的數據，我們收到了歐洲藥品管理局人用醫藥產品委員會的積極意見。

Turning to vaccines and infectious disease. We have taken a thoughtful and evidence-based approach to establishing a pipeline of pneumococcal vaccine candidates to address the specific needs of different populations, including infants and children, healthy adults and at-risk subgroups, starting with VAXNEUVANCE and now continuing with V116, our investigational 21-valent pneumococcal conjugate vaccine for adults.

轉向疫苗和傳染病。我們採取了深思熟慮和基於證據的方法來建立一系列候選肺炎球菌疫苗，以滿足不同人群的具體需求，包括嬰兒和兒童、健康成人和高危亞群，從 VAXNEUVANCE 開始，現在繼續到 V116，我們的疫苗用於成人的研究性 21 價肺炎球菌結合疫苗。

V116 a has potential to expand disease coverage to help protect against invasive pneumococcal disease in more than 85% of individuals 65 and older based on 2019 pre-pandemic CDC data. V116 includes 8 serotypes not currently covered by approved pneumococcal vaccines which are responsible for approximately 30% of invasive pneumococcal disease in individual 65 and older based on the same data.

根據 2019 年大流行前 CDC 數據，V116 a 有潛力擴大疾病覆蓋範圍，幫助 85% 以上的 65 歲及以上人群預防侵襲性肺炎球菌疾病。 V116 包括目前已批准的肺炎球菌疫苗未涵蓋的 8 种血清型，根據相同的數據，這些血清型導致 65 歲及以上個體中約 30% 的侵襲性肺炎球菌疾病。

Last week, we announced positive topline results from 2 Phase III trials evaluating V116. The STRIDE-003 trial demonstrated statistically significant immune responses in vaccine-naive adults compared to PCV20 for serotypes common to both vaccines; and the STRIDE-006 trial, demonstrating that V116 was immunogenic for all 21 pneumococcal serotypes in the vaccine among adults who previously received a pneumococcal vaccine at least 1 year prior to the study.

上週，我們宣布了兩項評估 V116 的 III 期試驗的積極結果。 STRIDE-003 試驗表明，對於兩種疫苗共有的血清型，與 PCV20 相比，未接種疫苗的成年人的免疫反應具有統計學顯著性； STRIDE-006 試驗表明，在研究前至少 1 年曾接種過肺炎球菌疫苗的成年人中，V116 對疫苗中的所有 21 種肺炎球菌血清型均具有免疫原性。

We are eager to share these findings and plan to present detailed data at an upcoming medical conference. As Rob noted, if approved, V116 would be the first pneumococcal conjugate vaccine specifically designed to address the serotypes that represent adult pneumococcal disease.

我們渴望分享這些發現，併計劃在即將召開的醫學會議上展示詳細數據。正如 Rob 指出的那樣，如果獲得批准，V116 將成為第一種專門針對代表成人肺炎球菌疾病的血清型而設計的肺炎球菌結合疫苗。

In infectious diseases, we received FDA approval for PREVYMIS for prophylaxis of cytomegalovirus disease for adult recipients of kidney transplant who are at high risk of CMV infection. Since 2017, PREVYMIS has been an important preventive option for CMV infection and disease in adult seropositive recipients of an allogeneic hematopoietic stem cell transplant, and we are pleased to build on the benefits it provides with this new approval.

在傳染病方面，我們的 PREVYMIS 獲得 FDA 批准，用於預防 CMV 感染高風險的成年腎移植受者的鉅細胞病毒病。自 2017 年以來，PREVYMIS 一直是同種異體造血幹細胞移植的成人血清陽性受者 CMV 感染和疾病的重要預防選擇，我們很高興通過這項新批准進一步發揮其優勢。

Progress continues in the cardiometabolic space. As Rob mentioned, following the remarkable results from the STELLAR trial, we have completed the submission to the FDA of the biologics license application for sotatercept for the treatment of adults with pulmonary arterial hypertension. Sotatercept had been granted breakthrough therapy designation by the FDA, and we look forward to work with the agency on its review. We are advancing our broad cardiovascular program, enrollment in Phase III trials for MK0616, our oral PCSK9 inhibitor, is anticipated to start later this month.

心臟代謝領域不斷取得進展。正如 Rob 提到的，繼 STELLAR 試驗取得顯著結果後，我們已完成向 FDA 提交 sotatercept 用於治療成人肺動脈高壓的生物製劑許可申請。 Sotatercept 已被 FDA 授予突破性療法認定，我們期待與該機構合作進行審查。我們正在推進廣泛的心血管計劃，我們的口服 PCSK9 抑製劑 MK0616 的 III 期試驗預計將於本月晚些時候開始。

In June, at the European Association for the Study of the Liver Meeting, positive results were presented from the Phase IIa randomized, active comparator-controlled, open-label study of efinopegdutide, our investigational GLP-1 glucagon receptor dual agonist, in patients with nonalcoholic fatty liver disease.

6 月，在歐洲肝臟研究協會會議上，Efinopegdutide（我們的研究性 GLP-1 胰高血糖素受體雙重激動劑）的 IIa 期隨機、活性比較對照、開放標籤研究在患有以下疾病的患者中呈現出積極結果：非酒精性脂肪肝。

Based on the findings from this study, efinopegdutide was granted Fast Track Designation by the FDA. We have now started a Phase IIb study to evaluate efficacy and safety in adult patients with pre-cirrhotic NASH.

根據這項研究的結果，efinopegdutide 被 FDA 授予快速通道指定。我們現已開始一項 IIb 期研究，以評估肝硬化前期 NASH 成年患者的療效和安全性。

Lastly, the FDA has accepted our resubmission of the new drug applications for gefapixant, our P2X3 receptor antagonist, for the treatment of refractory or unexplained chronic cough in adults. The PDUFA target action date is December 27, 2023. This follows the positive opinion from the CHMP in the European Union.

最後，FDA 已接受我們重新提交的 P2X3 受體拮抗劑 gefapixant 新藥申請，用於治療成人難治性或不明原因的慢性咳嗽。 PDUFA 的目標行動日期是 2023 年 12 月 27 日。這是在歐盟 CHMP 的積極意見之後進行的。

And finally, as Rob mentioned, this past quarter, we are delighted to welcome our new colleagues from Prometheus to Merck. The team is focused on advancing the clinical development program for MK7240, formerly PRA-023, and leveraging our combined strengths and expertise to better serve patients with immune-mediated diseases.

最後，正如 Rob 提到的，上個季度，我們很高興歡迎普羅米修斯的新同事來到默克。該團隊致力於推進 MK7240（以前稱為 PRA-023）的臨床開發計劃，並利用我們的綜合優勢和專業知識更好地為患有免疫介導疾病的患者提供服務。

In closing, we have established a regular cadence of late-phase pipeline progress and are proceeding with speed and rigor to advance a promising portfolio of diverse candidates, guided by science and focused on patient needs. Moving forward, we are well positioned to build on this momentum with further regulatory milestones, data readouts and clinical catalysts across therapeutic areas.

最後，我們已經建立了後期研發管線進展的常規節奏，並以科學為指導並以患者需求為重點，以快速、嚴謹的方式推進一系列有前景的多元化候選藥物。展望未來，我們已做好充分準備，在這一勢頭的基礎上，在治療領域取得進一步的監管里程碑、數據讀數和臨床催化劑。

And now I turn the call back to Peter.

現在我把電話轉回給彼得。

Thank you, Dean. Cedric. We're ready to take questions. We do appreciate analysts limiting themselves to 1 question so we can get to as many as possible today. Thank you.

謝謝你，迪恩。塞德里克.我們準備好回答問題。我們非常感謝分析師將自己限制在 1 個問題上，這樣我們今天就可以回答盡可能多的問題。謝謝。

(Operator Instructions) And our first question comes from Geoff Meacham with Bank of America.

（操作員說明）我們的第一個問題來自美國銀行的 Geoff Meacham。

Rob, you opened up the call with some comments on the IRA suit, so I wanted to ask you a little bit on that. I know it's hard to talk specifics on your strategy. But at a higher level, how important is it to get more companies to join the fray with Merck? And are there any milestones to watch for this fall on the suit beyond the initial 10 drugs being named next month?

羅布，您在通話開始時對 IRA 訴訟提出了一些評論，所以我想問您一些關於這個問題的問題。我知道很難詳細談論你的策略。但從更高的層面來看，讓更多公司加入與默克的競爭有多重要？除了下個月命名的最初 10 種藥物之外，今年秋天的訴訟還有什麼值得關注的里程碑嗎？

Yes, Geoff. I appreciate the question. And with regards to the IRA, obviously, our concern, and I think it's just worth reinforcing, is about what we see as an untenable challenge to innovation in the industry. And that's really the principal reason that drove us to bring the suit.

是的，傑夫。我很欣賞這個問題。關於 IRA，顯然，我們的擔憂（而且我認為值得加強）是我們認為對行業創新的挑戰。這確實是促使我們提起訴訟的主要原因。

But to your question, as you know now there are 4 drug companies actually in total, including Merck, have raised suits, all largely following the same types of arguments in addition to -- we have the chamber file a suit as well as the trade group pharma. So we're all moving forward. And our belief is that the provisions, particularly the negotiation provision of the IRA, is in violation of both the fifth and the first amendment of the constitution and is not a good policy. That's what brought us to bring to suit.

但對於你的問題，正如你現在所知，實際上總共有 4 家製藥公司，包括默克公司，提起了訴訟，除了我們讓商會和行業提起訴訟外，所有公司都基本上遵循相同類型的論點集團製藥。所以我們都在前進。我們認為，這些條款，特別是愛爾蘭共和軍的談判條款，違反了憲法第五修正案和第一修正案，不是一個好政策。這就是我們採取行動的原因。

As we look forward, we're going to take this to the fullest, which means we'll take it through District Court, and if need be, in the Circuit Court, and ultimately, to the Supreme Court. So really, that's the strategy. I don't want to comment on other companies and whether you're going to see additional companies come in beyond the 4 that are in now.

展望未來，我們將充分審理此案，這意味著我們將通過地方法院審理此案，如果需要，還可在巡迴法院審理，並最終向最高法院審理。確實，這就是策略。我不想評論其他公司以及是否會看到除了現在的 4 家公司之外還有其他公司加入。

As far as any kind of triggers to watch for, not really. Because while, obviously, we have set dates for the initial discovery and some of the initial hearings, this is going to take a while to play out. What I do think is highly likely is that we will be able to see this resolved by the time we get into the 2026 time frame. That's really what we're thinking about and moving through the various courts as needed. But I wouldn't really think you're going to see any large indicator in the near term. This is a longer-term play.

就任何需要注意的觸發因素而言，並非如此。因為，顯然，我們已經確定了初步發現和一些初步聽證會的日期，但這需要一段時間才能完成。我確實認為，當我們進入 2026 年的時間框架時，我們很有可能會看到這個問題得到解決。這確實是我們正在考慮的問題，並根據需要在各個法庭進行審理。但我真的不認為你會在短期內看到任何大型指標。這是一個長期的遊戲。

Our next question comes from Mohit Bansal with Wells Fargo.

我們的下一個問題來自富國銀行的 Mohit Bansal。

My question is regarding the onetime items. So Caroline, you mentioned regarding China for GARDASIL as well as KEYTRUDA in the U.S. Would you be able to quantify this a little bit? Just trying to understand the magnitude of how much [meat] is impacted by those onetime items.

我的問題是關於一次性物品。 Caroline，您提到了中國的 GARDASIL 以及美國的 KEYTRUDA。您能稍微量化一下嗎？只是想了解這些一次性物品對[肉類]的影響有多大。

Yes, of course, Mohit. Thank you for the questions. So first, talking about GARDASIL, there were no onetime items in the quarter for GARDASIL. We had exceptional growth. That growth was driven by every geography around the world. As we think about the second half of the year, though, we do expect shipments to China to be less than they were in the first half of the year and therefore expect the second half of the year growth to be slower than what we've achieved in the first half.

是的，當然，莫希特。謝謝你的提問。首先，談到 GARDASIL，本季度 GARDASIL 沒有一次性產品。我們取得了非凡的增長。這種增長是由世界各地各個地區推動的。不過，當我們考慮下半年時，我們確實預計對中國的出貨量將低於上半年，因此預計下半年的增長將慢於我們的預期上半年取得的成績。

For KEYTRUDA, we had a very strong quarter, and that strength was across all indications, including the earlier-stage cancer indications that we're launching. In the United States, we had sales of $3.9 billion, a growth of 21%. Now that growth included approximately $50 million of benefit because wholesaler buy-in in the second quarter of 2023 was slightly higher than the buy-in we saw in the second quarter of 2022.

對於 KEYTRUDA 來說，我們有一個非常強勁的季度，這種優勢遍及所有適應症，包括我們正在推出的早期癌症適應症。在美國，我們的銷售額為 39 億美元，增長 21%。現在，這一增長包括約 5000 萬美元的收益，因為 2023 年第二季度批發商的購買量略高於我們在 2022 年第二季度看到的購買量。

One of the distributors who has bought in has indicated that they expect to buy out in the third quarter. And the quantum of that buyout has been indicated to be $150 million. That said, we continue to expect strong growth from KEYTRUDA given the current indications we have as well as new launches to come.

一位已買入的經銷商表示，他們預計在第三季度買入。該收購金額預計為 1.5 億美元。也就是說，鑑於我們目前掌握的跡像以及即將推出的新產品，我們仍然預計 KEYTRUDA 會出現強勁增長。

Our next question comes from Louise Chen with Cantor.

我們的下一個問題來自 Louise Chen 和 Cantor。

I just wanted to ask you, on your Prometheus Phase III clinical trial, if you could give more color on the trial designs and then when you'll start those. And then if you'll pursue any other indications outside of IBD.

我只是想問你，在你的普羅米修斯 III 期臨床試驗中，你是否可以在試驗設計上提供更多的色彩，然後什麼時候開始這些試驗。然後您是否會尋求 IBD 之外的任何其他適應症。

Yes, so I'll take that. Thank you very much for the question in relationship to the Prometheus. Again, I just want to level set. For inflammatory bowel disease, there's a line of sight going -- anti-cytokines and then other mechanisms. Some of them actually have a black box. So we're very enthusiastic of moving forward with MK7240 or the TL1A.

是的，所以我會接受。非常感謝您提出與普羅米修斯有關的問題。再說一遍，我只是想設置水平。對於炎症性腸病，有一條視線——抗細胞因子和其他機制。其中一些實際上有一個黑匣子。因此，我們非常熱衷於推進 MK7240 或 TL1A。

In relationship to the start of Phase III, the integration is going extremely well. We anticipate to be starting that Phase III this year for ulcerative colitis. And as other data comes in terms of Crohn's disease and other diseases, we'll adjust appropriately. So the start of the Phase III, we are targeting this year, and the integration with our colleagues at Prometheus has gone extremely well.

隨著第三階段的開始，整合進展非常順利。我們預計今年將開始針對潰瘍性結腸炎的 III 期臨床試驗。隨著有關克羅恩病和其他疾病的其他數據的出現，我們將進行適當調整。因此，我們的目標是今年開始第三階段，與普羅米修斯同事的整合進展非常順利。

Your next question comes from Seamus Fernandez with Guggenheim Investments.

您的下一個問題來自古根海姆投資公司的謝默斯·費爾南德斯。

Great. My question actually is on the pneumococcal vaccine, V116. Dean, just hoping that you could clarify for us what statistically significant means and if that actually implies superiority on individual serotypes, superiority on a new metric that perhaps could be an overall superiority to Prevnar 20 in the STRIDE-3 results or if this is simply implying that it was statistically significant because it met the noninferiority margin. Just trying to get a little bit more clarification there.

偉大的。我的問題實際上是關於肺炎球菌疫苗 V116。 Dean，只是希望您能為我們澄清統計顯著性意味著什麼，以及這是否實際上意味著個體血清型的優越性、新指標的優越性，這可能是 STRIDE-3 結果中相對於 Prevnar 20 的整體優越性，或者這只是簡單的說明。意味著它具有統計顯著性，因為它滿足非劣效性界限。只是想在那裡得到更多的澄清。

And as a follow-up to that, just wanted to get a better sense of, if you believe the data, as it sits today, opens up a meaningful opportunity in international markets, where national immunization programs have been reluctant to use pneumococcal vaccine in the adult setting largely because of herd immunity.

作為後續行動，只是想更好地了解，如果您相信今天的數據，在國際市場上開闢了一個有意義的機會，在國際市場上，國家免疫計劃一直不願意在全球使用肺炎球菌疫苗。成人環境很大程度上是因為群體免疫。

Yes. Thank you so much. So I'll just add a topline, just say I am pleased with the data, and it gives me confidence in the path forward for V116. It's not just the data that's going to be presented. The data is going to be presented relatively soon at an international conference, but it's also the path to regulatory approval and eventually in the U.S. to ACIP. So this data is strong. And I just would recount that if approved, as you point out, it would be the first, the first adult-specific pneumococcal vaccine, and it covers 85% of all invasive pneumococcal disease in adults greater than -- or older than 65.

是的。太感謝了。所以我只想添加一條頂線，只是說我對這些數據感到滿意，這讓我對 V116 的前進道路充滿信心。這不僅僅是要呈現的數據。這些數據將很快在國際會議上公佈，但這也是獲得監管部門批准並最終在美國獲得 ACIP 的途徑。所以說這個數據是很強的。我只想重述一下，正如您所指出的，如果獲得批准，這將是第一個、第一個成人專用肺炎球菌疫苗，它覆蓋 85% 的 65 歲以上成人的所有侵襲性肺炎球菌疾病。

The way that I think about the vaccine, it's a 21-valent, is that there's 10 shared with PCV20 and there's 11 uniques with PCV20. And as one looks at the data that will be coming out, one would see that in the shared one, they're -- right, the question always in the shared one is, is there -- how does it compare with the shared ones with PCV20? And in that situation, it has met the non-inferior boundaries. And so I want to be clear about that.

我對疫苗的看法是，它是 21 價的，有 10 個與 PCV20 共享，有 11 個與 PCV20 獨特。當人們查看即將出現的數據時，人們會發現在共享數據中，它們是——對的，共享數據中始終存在的問題是，是否存在——它與共享數據相比如何與PCV20？在這種情況下，它已經達到了非劣質界限。所以我想澄清這一點。

Clearly, the 11 unique serotypes are unique to V116. And so the issue for that is whether they're statistically significant, whether they're clinically meaningful. And I'm confident as we move forward that, that will become clear. It's really hard to talk about superiority or anything like this when you're talking about the 11 unique serotypes.

顯然，這 11 種獨特的血清型是 V116 所獨有的。因此，問題在於它們是否具有統計學意義，是否具有臨床意義。我相信，隨著我們繼續前進，這一點將會變得清晰。當你談論 11 種獨特的血清型時，真的很難談論優越性或類似的事情。

But I just want to step back because you've sort of touched on it a little bit. It validates the strategy of having an age-appropriate serotype coverage. Just to remind everyone, V114 is at 15-valent. It has 22F, 33F and has improved immunogenicity for serotype 3. And most importantly, it provides impotence protection within the first year of life.

但我只是想退後一步，因為你已經觸及了一點。它驗證了具有適合年齡的血清型覆蓋的策略。提醒大家一下，V114 的價格是 15 價。它具有 22F、33F，並提高了血清型 3 的免疫原性。最重要的是，它在生命的第一年內提供陽痿保護。

So that's how we thought about that age-appropriate serotype coverage. And then V116 clearly is 21-valent 85% invasive pneumococcal disease and then is driving towards the adult market. But I'll turn it over to Rob to give some view of the prospects commercially, how we see it.

這就是我們如何考慮適合年齡的血清型覆蓋範圍。然後V116顯然是21價85%侵襲性肺炎球菌疾病，然後正在向成人市場發展。但我會把它交給羅布，讓他對商業前景以及我們如何看待它給出一些看法。

Yes. No, thank you. Thanks, Dean, and thanks, Seamus, for the question. As Dean just summarized, the data is pretty much about as good as you could expect. So as we sit here today, we're very confident in what this vaccine can offer both in the United States, and we do believe there is a meaningful opportunity for us to take this internationally. So we're going to have to see how it plays out.

是的。不，謝謝。謝謝迪安，也謝謝西莫提出的問題。正如迪恩剛剛總結的那樣，數據幾乎與您預期的一樣好。因此，當我們今天坐在這裡時，我們對這種疫苗可以在美國提供的服務非常有信心，並且我們確實相信我們有一個有意義的機會在國際上推廣這種疫苗。所以我們必須看看結果如何。

But as we sit here today, we are excited about this product and ready to launch as soon as we get approval to do so because we do think, as Dean pointed out, we give 85% coverage. That's 30% better than Prevnar 20. It's also better than any other vaccine currently in development. So we think this is an important drug. And when you combine it with what we have with VAXNEUVANCE, our pneumococcal franchise is a significant opportunity that we think could be multibillion as we go out into the future. So this is something we're invested in and we're going to continue to drive aggressively.

但當我們今天坐在這裡時，我們對這個產品感到興奮，並準備在獲得批准後立即推出，因為我們確實認為，正如 Dean 指出的那樣，我們提供了 85% 的覆蓋率。這比 Prevnar 20 好 30%。它也比目前正在開發的任何其他疫苗都要好。所以我們認為這是一種重要的藥物。當你將其與我們擁有的 VAXNEUVANCE 結合起來時，我們的肺炎球菌特許經營權是一個重要的機會，我們認為隨著我們走向未來，這個機會可能會達到數十億美元。所以這是我們投資的事情，我們將繼續積極推動。

Our next question comes from Akash Tewari with Jefferies Group.

我們的下一個問題來自 Jefferies Group 的 Akash Tewari。

Can you hear me?

你能聽到我嗎？

Yes.

是的。

Okay. So prior to Prometheus, you guys had a pretty limited presence in immunology. Is there any urgency to build out that part of the business externally via BD? And does your team have any view on the FcRn inhibitor class, how large it may end up being over time? And how maybe one of those assets could fit strategically with your plans in this category?

好的。所以在普羅米修斯之前，你們在免疫學方面的存在相當有限。通過 BD 外部拓展這部分業務是否存在緊迫性？您的團隊對 FcRn 抑製劑類別有什麼看法嗎？隨著時間的推移，它最終可能會有多大？這些資產中的一項如何能夠戰略性地符合您在這一類別中的計劃？

Yes. Akash, thanks for the question. I'll let Dean speak to the science side of this. But from a business perspective, we actually have had a presence in immunology. You might recall that across Europe and outside the United States, we sold Remicade. So we've been involved -- and Symphony. So we've been involved in this space.

是的。阿卡什，謝謝你的提問。我會讓迪恩談談這個問題的科學方面。但從商業角度來看，我們實際上已經涉足免疫學領域。您可能還記得，我們​​在歐洲和美國以外的地區銷售 Remicade。所以我們一直參與其中——還有 Symphony。所以我們一直參與這個領域。

As we sit here today, we don't see a significant commercial build. We think actually we can leverage a lot of the capabilities we have. We will invest in this area for success. And then Dean can comment, but we have been building on the science side. Obviously, we did the Pandion acquisition, building off the learning from immuno-oncology into the immunology space, and now with Prometheus, as well as we brought in some really top talent in both the discovery and development area in this area.

當我們今天坐在這裡時，我們沒有看到重大的商業建築。我們認為實際上我們可以利用我們擁有的很多能力。我們將在這一領域進行投資以取得成功。然後迪恩可以發表評論，但我們一直在科學方面進行建設。顯然，我們收購了 Pandion，將免疫腫瘤學的學習擴展到免疫學領域，現在又收購了 Prometheus，我們還引進了該領域發現和開發領域的一些真正頂尖的人才。

So I think we're well positioned to drive this business. And obviously, we're always open to continuing to look for additional business development. But it's not something I think we have to do to fill a gap. It's more of how do we continue to augment for further growth.

所以我認為我們有能力推動這項業務。顯然，我們始終願意繼續尋求額外的業務發展。但我認為這不是我們必須做的事情來填補空白。更多的是我們如何繼續增強以實現進一步增長。

Yes, I will just answer scientifically. I mean, what we've done with external partnerships or, I should say, acquisitions with Pandion and Prometheus, it should be very clear how interested we are in those fields. I would also note that each one of them has a lead compound that the focus is, but there are also follow-on compounds that come through that will be important.

是的，我只是科學地回答。我的意思是，我們與外部合作夥伴關係，或者我應該說，與 Pandion 和 Prometheus 的收購，應該非常清楚我們對這些領域的興趣。我還要指出的是，它們中的每一個都有一種重點關注的先導化合物，但也有一些後續化合物也很重要。

And especially in relationship to both of them, Prometheus and Pandion, we've been blessed by the fact that many of those top talent have chosen to continue with us. So we're very confident in this build. The other point that I would make is that separate to those external, there is an internal pipeline that is moving reasonably fast and will become more clear in the clinical space in the next few years as well.

尤其是與 Prometheus 和 Pandion 這兩個人的關係，我們很幸運，許多頂尖人才選擇繼續與我們合作。所以我們對這個構建非常有信心。我要說的另一點是，與外部管道分開，有一個內部管道正在相當快地發展，並且在未來幾年的臨床領域也將變得更加清晰。

The next question comes from Chris Schott with JPMorgan.

下一個問題來自摩根大通的克里斯·肖特。

Just a clarification to an earlier question and a follow-up. Just on KEYTRUDA and growth moderating in the second half. I guess, in addition to the U.S. wholesaler dynamic, I think you mentioned some EU price pressures. I just wanted to clarify, is that something incremental that you're expecting in the second half or more just a continuation of pressures you're already seeing in the first half of the year?

只是對之前的問題和後續問題的澄清。就 KEYTRUDA 而言，下半年增長放緩。我想，除了美國批發商的動態之外，我認為您還提到了一些歐盟的價格壓力。我只是想澄清一下，您所期望的下半年或更多的增量是否只是您在上半年已經看到的壓力的延續？

And then my other question was just on business development. Just more broadly, the company has been pretty active over the past 12 to -- or I guess, 12 to 24 months. I guess what are just the priorities at this point? And should we think about a pause in activity post-Prometheus? Or is it really still full speed ahead in terms of looking at further transactions?

然後我的另一個問題是關於業務發展。更廣泛地說，該公司在過去 12 到 12 到 24 個月裡一直非常活躍。我想目前的優先事項是什麼？我們是否應該考慮在普羅米修斯之後暫停活動？或者說，在考慮進一步的交易方面，它真的仍然在全速前進嗎？

Thank you for the question, Chris. This is Caroline. In terms of the KEYTRUDA expectations for the remainder of the year, as we noted, we do expect continued price pressure in Europe. Two elements to that. The first is as we continue to launch new indications, we will see likely price reductions as we launch those new indications, but we'll see volume growth as we impact more patients and therefore drive revenue.

謝謝你的提問，克里斯。這是卡羅琳。正如我們所指出的，就 KEYTRUDA 對今年剩餘時間的預期而言，我們確實預計歐洲將繼續面臨價格壓力。有兩個要素。首先，隨著我們繼續推出新的適應症，我們將看到可能的價格下降，因為我們推出這些新的適應症，但隨著我們影響更多的患者，我們將看到銷量的增長，從而推動收入。

We also do have the impact of some austerity measures or changes in reimbursement measures in some of our European countries, specifically in Germany, with the shortening of the AMNOG review time line as well as in the U.K. with the VPAS. So as we look forward, we do see that those pricing headwinds sustain, but we are confident in the continued growth that we will drive for KEYTRUDA.

我們也確實受到一些歐洲國家的一些緊縮措施或報銷措施變化的影響，特別是在德國，AMNOG 審查時間線的縮短，以及英國 VPAS 的影響。因此，展望未來，我們確實看到這些定價阻力持續存在，但我們對推動 KEYTRUDA 的持續增長充滿信心。

Yes. And Chris, on the business development question. As Caroline noted in the prepared remarks, we continue to have ample firepower to do deals. And while I can tell you, I feel very confident, and I know the team feels very confident about the progress we're making with our internal pipeline and with the BD we've already done, if you look forward, we're going to be -- we've either recently announced or will be announcing a number of important Phase III assets across oncology, with basically every area of the business, cardiometabolic, what we see in vaccines as well as important upcoming launches. We've talked about V116 data, sotatercept. We can go down the line.

是的。克里斯，關於業務發展問題。正如卡羅琳在準備好的發言中指出的那樣，我們仍然有充足的火力來做交易。雖然我可以告訴你，我感到非常有信心，而且我知道團隊對我們在內部管道和我們已經完成的 BD 方面取得的進展非常有信心，如果你期待的話，我們將會我們最近宣布或將宣布跨腫瘤學的許多重要的三期資產，基本上涉及業務的每個領域，心臟代謝，我們在疫苗中看到的以及即將推出的重要產品。我們已經討論過V116數據，sotatercept。我們可以繼續往下走。

So I feel very good about the progress. That being said, we continue to have a priority to do business development. So you should not necessarily expect a slowdown. If and when assets that bring important scientific opportunities present themselves, where we see an alignment with strategy and where we can see value creation, we have the capacity and we will be and are willing to act on those. So we're actively looking and we'll continue to drive deals because, while I feel very good about where we are, we're talking about trying to build a sustainable engine well into the next decade. And we want to continue to add to the firepower we have coming out of our own discovery and development labs as well.

所以我對進展感到非常滿意。話雖如此，我們仍然優先考慮業務發展。因此，您不一定會預期經濟會放緩。如果當帶來重要科學機會的資產出現時，我們看到與戰略的一致性以及我們可以看到價值創造的地方，我們就有能力、我們將並且願意採取行動。因此，我們正在積極尋找並將繼續推動交易，因為雖然我對我們的現狀感到非常滿意，但我們正在談論努力在下一個十年建立一個可持續的引擎。我們也希望繼續增強我們自己的發現和開發實驗室的火力。

Our next question comes from Dana Graybosch with Leerink Partners.

我們的下一個問題來自 Leerink Partners 的 Dana Graybosch。

I have a question on KEYTRUDA. I wonder if you could talk about how much remaining headroom you see for KEYTRUDA growth in some of the early-stage markets that you've been mentioning, including triple-negative breast cancer, RCC? I believe it's probably stage 2 melanoma and lung cancer, both in the U.S. and outside the U.S.

我對 KEYTRUDA 有疑問。我想知道您能否談談您認為 KEYTRUDA 在您提到的一些早期市場（包括三陰性乳腺癌、RCC）中的增長空間還有多少？我相信這可能是 2 期黑色素瘤和肺癌，無論是在美國還是在美國境外。

Yes. So I'll start and Caroline can add in if I miss something here. But the high-level answer is we see a lot of room for continued growth, both in early-stage cancers, the ones where we have current indications, and importantly, ones that are still coming. So kind of running through the list, triple-negative breast cancer, obviously,has driven important growth, both in the adjuvant, neoadjuvant and metastatic setting.

是的。那麼我就開始了，如果我錯過了什麼，卡羅琳可以補充。但高層次的答案是，我們看到了很大的持續增長空間，無論是在早期癌症中，在我們目前有跡象的癌症中，重要的是，在那些仍在出現的癌症中。綜上所述，三陰性乳腺癌顯然推動了輔助、新輔助和轉移性乳腺癌的重要增長。

It was a big driver of growth last year in the United States. It's a driver of growth in the U.S. this year. That will slow into next year in the U.S., but we're seeing it picking up outside the United States because we're at an earlier phase in the launch across the world. So that will continue to be an important area.

這是去年美國經濟增長的一大推動力。這是今年美國經濟增長的驅動力。在美國，這種情況將在明年放緩，但我們看到它在美國以外地區有所回升，因為我們正處於全球發布的早期階段。因此，這將繼續是一個重要領域。

And then you saw, today, we announced important data in KEYNOTE-756. So that is promising for a future indication that we could potentially see coming down the path in early-stage breast cancer as well. If you look at lung cancer, we continue to expect growth. In fact, we're growing in lung cancer now, both internationally and in the U.S. But importantly, what's going to drive growth longer term is as we continue to penetrate into earlier lines of therapy.

然後你看到，今天，我們在 KEYNOTE-756 中公佈了重要數據。因此，這對於未來的跡象來說是有希望的，我們也有可能看到早期乳腺癌的發展。如果你看看肺癌，我們仍然預計會出現增長。事實上，無論是在國際上還是在美國，我們現在的肺癌治療都在增長。但重要的是，從長遠來看，推動增長的是我們繼續滲透到早期的治療領域。

Obviously we're early in the launch of KEYNOTE-091 in the United States and in certain markets outside the U.S. We're very excited about what KEYNOTE-761 could be and how that will help drive growth in non-small cell lung cancer. And then across RCC, continued good growth in the adjuvant setting, good growth in metastatic.

顯然，我們正處於在美國和美國以外的某些市場推出 KEYNOTE-091 的早期階段。我們對 KEYNOTE-761 的前景以及它將如何幫助推動非小細胞肺癌的增長感到非常興奮。然後在整個腎細胞癌中，在佐劑環境中持續良好的生長，在轉移中良好的生長。

We have what's coming with WELIREG, which is going to continue to broaden our opportunity there. Great growth coming in bladder cancer. I'll stop there, because I could go on but we want to get to other questions. The short answer is a lot of growth, a lot of opportunity with KEYTRUDA. We're going to make a big difference in a lot of patients' lives as we move forward with this drug.

我們擁有 WELIREG 即將推出的產品，它將繼續擴大我們在那裡的機會。膀胱癌的巨大增長。我就到此為止，因為我可以繼續說下去，但我們想討論其他問題。簡短的回答是 KEYTRUDA 帶來很大的增長和很多機會。隨著我們繼續開發這種藥物，我們將為許多患者的生活帶來巨大的改變。

The next question comes from Tim Anderson with Wolfe Research.

下一個問題來自沃爾夫研究公司的蒂姆·安德森。

I have a question for Dean on the TROP2 asset from Kelun. Kind of a key debate and a newer debate has been the role of the TROP2 biomarker and whether higher expression predicts better response. And it's come into focus more recently, partly because of Aztra's topline on their lung trial, as well as the Phase III trial, they started earlier this year. So I'd like to get your views on the role of this biomarker. And specifically, do you plan to include that as a stratification factor in any of your upcoming Phase III trials?

我有一個關於科倫 TROP2 資產的問題要問 Dean。 TROP2 生物標誌物的作用以及更高的表達是否預示著更好的反應是一種關鍵的爭論和更新的爭論。它最近成為人們關注的焦點，部分原因是 Aztra 在肺部試驗以及今年早些時候開始的 III 期試驗中表現出色。所以我想听聽您對這種生物標誌物作用的看法。具體來說，您是否計劃將其作為分層因素納入即將進行的任何 III 期試驗？

Yes. Thank you very much for that question about TROP2-ADCs, especially in relation to the lung. So as a broader picture, I would just say that, initially, the focus will be in the metastatic, and then depending on how those play out, it may go into earlier stages of cancer as well more broadly. But as we talk about lung cancer, the critical question that the field has to answer, us and others, is whether or not you can dethrone KEYNOTE-189.

是的。非常感謝您提出有關 TROP2-ADC 的問題，特別是與肺有關的問題。因此，從更廣泛的角度來看，我只想說，最初的重點將是轉移，然後根據這些進展的情況，它也可能更廣泛地進入癌症的早期階段。但當我們談論肺癌時，我們和其他人必須回答的關鍵問題是，你是否可以推翻 KEYNOTE-189。

So we're all trying to dethrone Merck's standard of care, which is pembro plus chemo, in first-line in metastatic non-small cell lung cancer. I will just say, lots of people have tried to do it, including us, and it's a high bar to try to overcome. And so the issue for us is how do you overcome that? Because I think if you can prove that an ADC can do that, that will be very important for the field.

因此，我們都在努力推翻默克的治療標準，即 pembro 加化療，作為轉移性非小細胞肺癌的一線療法。我只想說，很多人都嘗試過這樣做，包括我們，這是一個需要克服的很高的障礙。所以我們面臨的問題是如何克服這個問題？因為我認為如果你能證明 ADC 可以做到這一點，那對於這個領域來說將非常重要。

And so we have our data. It's -- we are very comfortable with the safety. But we think that it may be important to maximize the impact of the TROP2-ADC so that you can give something meaningful -- a meaningful benefit over KEYNOTE-189. So I think the biomarker could be important if what you're trying to do is displace KEYNOTE-189 because KEYNOTE-189 is a high bar to beat.

這樣我們就有了數據。我們對安全感到非常滿意。但我們認為，最大限度地發揮 TROP2-ADC 的影響可能很重要，這樣您就可以提供一些有意義的東西——比 KEYNOTE-189 更有意義的好處。因此，我認為如果您想要取代 KEYNOTE-189，生物標誌物可能很重要，因為 KEYNOTE-189 是一個需要超越的高標準。

The next question comes from Chris Shibutani with Goldman Sachs.

下一個問題來自高盛的 Chris Shibutani。

With sotatercept, you acknowledged the progress of the filing completed in the third quarter here. Could you just remind us in terms of what your expectations are for potential label? Any nuances here in particular with regard to secondary endpoints that you think would be meaningful from a commercial standpoint? And then recognizing that you have had some commercial footprint, what should we think about in terms of what's going to be required with the potential launch in 2024? And similarly, with reimbursement for a new product, what should we think in terms of the cadence? We do recognize that physicians have been quite aware and enthusiastic about the data.

對於 sotatercept，您在此確認了第三季度完成的備案進度。您能否提醒我們您對潛在標籤的期望是什麼？這裡有任何細微差別，特別是您認為從商業角度來看有意義的次要終點嗎？然後認識到您已經有了一些商業足跡，我們應該考慮 2024 年可能推出的產品需要什麼？同樣，對於新產品的報銷，我們應該如何考慮節奏？我們確實認識到，醫生們對這些數據非常了解並且充滿熱情。

Yes. So let me take the science part of that, Chris. In relationship to sotatercept in the STELLAR trial, I think the label in the U.S. will be reasonably clear and follow that of -- what the STELLAR trial is. I think one of the things that was really important is that when we declared it, we didn't just declare a 6-minute walk. We declared a time to clinical worsening and death, which was really important because I think that creates a different scenario for us than what we had predicted previously in our ability to go to market outside of the U.S. So I think that will be in the label within the FDA.

是的。所以讓我來談談其中的科學部分，克里斯。關於 STELLAR 試驗中的 sotatercept，我認為美國的標籤將相當清晰，並遵循 STELLAR 試驗的標籤。我認為真正重要的事情之一是，當我們宣布這一點時，我們不僅僅是宣布步行 6 分鐘。我們宣布了臨床惡化和死亡的時間，這非常重要，因為我認為這為我們創造了一個與我們之前預測的不同的場景，即我們進入美國以外市場的能力，所以我認為這將出現在標籤中FDA 內。

But I think where it's important is it may change the speed with which the international markets adopt sotatercept. I hope that gives you that general sense. But as we move this forward, we are looking, and I think we've said previously that we would have the file complete. And I think given the general sense, we thought that we would be launching, at least within the U.S., in the earlier part of 2024.

但我認為重要的是它可能會改變國際市場採用 sotatercept 的速度。我希望這能給你一般的感覺。但隨著我們向前推進，我們正在尋找，而且我想我們之前已經說過我們將完成該文件。我認為，從一般意義上講，我們認為我們將在 2024 年初推出，至少在美國境內。

Yes. Chris, this is Rob. So on the question of our infrastructure support and launch, we're actually well positioned. I would remind you that we currently market Adempas outside the United States. That is PAH. So outside the U.S., we're going to be able to leverage our relationships and our infrastructure there. We -- obviously, we'll add to it. And then in the United States, this is in its first indications. Anyway, more of a rare disease.

是的。克里斯，這是羅布。因此，在我們的基礎設施支持和啟動問題上，我們實際上處於有利位置。我想提醒您的是，我們目前在美國境外銷售 Adempas。那就是多環芳烴。因此，在美國之外，我們將能夠利用我們在那裡的關係和基礎設施。顯然，我們會添加它。然後在美國，這是最初的跡象。無論如何，更多的是一種罕見的疾病。

You're looking at about 150 specialty centers in the United States have actually prescribed this. So this -- we're not talking a large commercial footprint. This is more of a rare disease type of launch. And we've been focused on building out capabilities, particularly as we think about medical affairs, science liaisons and how do we manage the relationships, kind of the complex journey of patients facing these diseases with their physicians. A lot of work is already underway.

你會看到美國大約有 150 個專科中心實際上已經開出了這種處方。所以，我們並不是在談論巨大的商業足跡。這更像是一種罕見疾病類型的發射。我們一直專注於建設能力，特別是當我們考慮醫療事務、科學聯絡以及我們如何管理關係，以及患者與醫生面對這些疾病的複雜旅程時。許多工作已經在進行中。

So I'm quite confident we'll be prepared for our launch, both in the U.S. and outside the U.S. Because as Dean mentioned, our belief, what this can be globally is much bigger than when we originally did the deal given what we expect to be the label we will see. As far as the reimbursement goes, to your point, this drug, especially in the United States is very well known. The specialists in the area already understand it. They're already waiting for it. We know there are patients waiting for it. So I think you could expect a pretty fast uptake of the drug, especially in the United States.

因此，我非常有信心，我們將為在美國和美國以外的市場推出做好準備。因為正如迪恩提到的，我們相信，鑑於我們的預期，這在全球範圍內的影響力比我們最初進行交易時要大得多成為我們將看到的標籤。就報銷而言，就您而言，這種藥物，尤其是在美國，是非常有名的。該領域的專家已經了解這一點。他們已經在等待了。我們知道還有病人在等待。所以我認為你可以預期這種藥物會很快被吸收，尤其是在美國。

Outside the U.S. we're going to have to drive for reimbursement. That will take longer. But I think in both cases, our expectations and confidence in both the speed of uptake and the potential total volume or total revenue potential of this drug is more significant today than when we did the deal, just given the strength of the stellar results and what we continue to expect. So we're quite bullish on this.

在美國境外，我們將不得不開車尋求報銷。那會需要更長的時間。但我認為，在這兩種情況下，我們對這種藥物的吸收速度和潛在總量或總收入潛力的期望和信心今天比我們進行交易時更重要，考慮到出色的結果的強度以及什麼我們繼續期待。所以我們對此非常看好。

Next question comes from Andrew Baum with Citi.

下一個問題來自花旗銀行的安德魯·鮑姆 (Andrew Baum)。

A clarification for Dean and then a question for Rob. So just in regards to the previous question about TROP, just so I'm clear, do you plan to stratify or select for TROP2 expression in your first-line -- first and second-line outcome trials, particularly for those patients with actionable -- without actionable genomic mutation? So are you actually going to stratify a select within the trials aimed at that patient cohort?

先向 Dean 進行澄清，然後向 Rob 提出問題。因此，關於之前關於 TROP 的問題，我很清楚，您是否計劃在一線 - 一線和二線結果試驗中對 TROP2 表達進行分層或選擇，特別是對於那些可採取行動的患者 - - 沒有可操作的基因組突變？那麼，您真的要在針對該患者隊列的試驗中對選擇進行分層嗎？

And then second for Rob, if your efforts to repeal or amend the IRA are unsuccessful, would you delay the launch of your oral PCSK9 until you have outcome data in hand?

其次，Rob，如果您廢除或修改 IRA 的努力不成功，您會推遲啟動口服 PCSK9 直到您掌握結果數據嗎？

Yes. So let me just take care. I don't want to get too ahead of what's on clinical trials. But as I've emphasized, especially when we're thinking about first-line non-small cell lung cancer, given what we think is a standard of care, we think that it will be important to review that in the setting of a biomarker selection. And I just kind of want to leave it at that. The precise design will come out as the teams actually roll it out. But we think that, as I've said before, the biomarker strategy will be very important for our push of TROP2-ADCs into lung cancer.

是的。所以讓我照顧一下。我不想太提前了解臨床試驗的情況。但正如我所強調的，特別是當我們考慮一線非小細胞肺癌時，考慮到我們認為的護理標準，我們認為在生物標誌物的設置中對其進行審查非常重要選擇。我只是想就此罷休。當團隊實際推出時，精確的設計就會出來。但我們認為，正如我之前所說，生物標誌物策略對於我們將 TROP2-ADC 推向肺癌非常重要。

Yes. And on the question of how we think about the oral PCSK9 and would we delay for an outcome study, I think it's too early to make that kind of decision because, frankly, how we think about the outcome study and whether or not -- and what kind of label we get before we have an outcome study is still something we're working through. So we need to understand the label. We need to understand the timing of the outcome study. And until I know all those points, I wouldn't want to get ahead of where we would be. So more to come. We've got some time on that one.

是的。關於我們如何看待口服 PCSK9 以及我們是否會推遲進行結果研究的問題，我認為現在做出這種決定還為時過早，因為坦率地說，我們如何看待結果研究以及是否 - 和在進行結果研究之前我們會得到什麼樣的標籤，這仍然是我們正在研究的問題。所以我們需要了解標籤。我們需要了解結果研究的時間安排。在我了解所有這些要點之前，我不想超越我們的目標。未來還會有更多。我們有一些時間來討論這個問題。

Our last question comes from Steve Scala with Cowen.

我們的最後一個問題來自史蒂夫·斯卡拉和考恩。

A question for Dean on the KEYTRUDA data in periadjuvant ER-positive breast cancer. Should we expect the EFS to read out well before the KEYTRUDA LOE so the commercial opportunity can be realized? How do you think it stacks up to CDK4/6 inhibitors in the adjuvant setting? And is there potential to file for neoadjuvant approval in the meantime?

問 Dean 關於 ER 陽性乳腺癌輔助治療期間 KEYTRUDA 數據的問題。我們是否應該期望 EFS 早於 KEYTRUDA LOE 讀出，以便實現商業機會？您認為它在輔助治療中與 CDK4/6 抑製劑的效果如何？同時是否有可能申請新輔助治療批准？

So I'll just step back a little bit. So the KEYNOTE-756, as you've noted, is an ER-positive/HER2-negative. It's earlier stage. It is neoadjuvant/adjuvant. We've given -- based on the data that we've given in the press release, that it's at CR in relationship to an interim. As you know, EFS is already event-based. And so the question is how fast do you accrue events in relationship to that. And our hope is -- the answer to your question is yes, but we will just have to see because they are event-based.

所以我會退一步。因此，正如您所指出的，KEYNOTE-756 是 ER 陽性/HER2 陰性。還處於早期階段。它是新佐劑/佐劑。根據我們在新聞稿中提供的數據，我們已經表示，它處於與臨時相關的 CR 狀態。如您所知，EFS 已經是基於事件的。所以問題是你積累與此相關的事件的速度有多快。我們的希望是——你的問題的答案是肯定的，但我們只需要看看，因為它們是基於事件的。

I would just highlight, in KEYNOTE-522, which is triple negative breast, which is also earlier stage, which is also neoadjuvant/adjuvant and also at a positive path CR, we've demonstrated that path CR is a predictive of the future, followed up by EFS. And so we'll have to just watch that data as that data advances.

我想強調的是，在 KEYNOTE-522 中，這是三陰性乳腺癌，也是早期階段，也是新輔助/輔助，也是處於積極路徑 CR，我們已經證明路徑 CR 是對未來的預測，隨後是EFS。因此，我們只能隨著數據的進展來觀察這些數據。

Great. Thanks, Steve. Rob?

偉大的。謝謝，史蒂夫。搶？

Yes. Well, I appreciate everyone investing time today with the call. And just really maybe to conclude, I just want to reinforce how confident I am about how well positioned we are to continue to drive value creation for patients, for shareholders and for all of our stakeholders well into the future. And again, I just really want to thank all of my great colleagues across the globe for their substantial efforts.

是的。嗯，我感謝大家今天花時間參加這次電話會議。也許最後得出的結論是，我只是想強調，我對我們在未來繼續為患者、股東和所有利益相關者創造價值的能力充滿信心。再次，我真的想感謝全球所有偉大的同事所做的巨大努力。

We really do look forward to building on the progress we have in the second half of 2023 and beyond. And hopefully, what you took from our comments today, both prepared and in the Q&A, is our confidence in the progress we're making and, really, the difference we can make for patients across an ever-broadening area of therapeutic possibility. So it's exciting, what we have in front of us right now. Thank you.

我們確實期待在 2023 年下半年及以後取得的進展再接再厲。希望您從我們今天的評論（包括準備好的評論和問答中）得到的是我們對我們正在取得的進展的信心，以及我們實際上可以在不斷擴大的治療可能性領域為患者帶來的改變的信心。所以，我們現在所面臨的一切是令人興奮的。謝謝。

Great. Thank you all.

偉大的。謝謝你們。