美國安進 (AMGN) 2021 Q2 法說會逐字稿

This is Erica, and I will be your conference facilitator today for Amgen's Second Quarter 2021 Financial Results Conference Call. (Operator Instructions)

我是 Erica，今天我將擔任安進公司 2021 年第二季財務業績電話會議的主持人。 （操作說明）

I would now like to introduce Arvind Sood, Vice President of Investor Relations. Mr. Sood, you may now begin.

現在我謹介紹投資人關係副總裁阿文德‧蘇德先生。蘇德先生，您可以開始了。

Erica, thank you. Good afternoon, everybody. Welcome to our Q2 call.

艾麗卡，謝謝。大家下午好。歡迎參加我們的第二季電話會議。

I think the 3 key themes for this quarter are great execution in a challenging environment, pipeline advancement and smart and strategic business development. Lots to cover, so let's jump right in.

我認為本季的三大關鍵主題是：在充滿挑戰的環境中出色執行、推進銷售管道以及明智且具有戰略意義的業務拓展。內容很多，讓我們馬上開始。

Slides are up. Quick reminder that we'll use non-GAAP financial measures in our presentation, and some of the statements will be forward-looking statements. Our SEC filings identify factors that could cause our actual results to differ materially. So with that, I would like to turn the call over to our Chairman and CEO, Bob Bradway. Bob?

幻燈片已上傳。再次提醒一下，我們的簡報將使用非GAAP財務指標，並且部分陳述屬於前瞻性陳述。我們提交給美國證券交易委員會（SEC）的文件列出了可能導致實際業績與預期有重大差異的因素。那麼，接下來我將把電話交給我們的董事長兼執行長鮑伯‧布拉德韋。鮑伯？

Okay. Thank you, Arvind, and hello, everyone, and thank you for joining our call. Through the first 6 months of the year, Amgen has continued to execute well, driving demand for our current products globally while also paving the way for growth from future products.

好的。謝謝Arvind，大家好，謝謝各位參加我們的電話會議。今年前六個月，安進繼續保持良好的業績，在全球範圍內推動了現有產品的需求，同時也為未來產品的成長奠定了基礎。

Total revenues in the second quarter increased 5% over the prior year and 11% over the prior quarter. We achieved this growth despite the lingering effects of COVID-19 and increased competition in many of our therapeutic categories.

第二季總營收年增5%，季增11%。儘管受到新冠疫情持續影響，且在許多治療領域面臨日益激烈的競爭，我們依然實現了這一成長。

We continue to see strong volume-driven growth from Repatha, Otezla, Prolia and EVENITY and a number of our oncology biosimilar -- or excuse me, oncology medicines as well, all of which address significant health challenges.

我們繼續看到 Repatha、Otezla、Prolia 和 EVENITY 以及我們的一些腫瘤生物相似藥（或抱歉，腫瘤藥物）實現了強勁的銷售成長，所有這些藥物都旨在應對重大的健康挑戰。

We also saw strong growth in the quarter from our biosimilars, supporting our commitment to deliver value to health care systems around the world. We generated volume growth of 22% outside the United States, and we're particularly encouraged by our progress in the Asia Pacific region where 2 notable approvals in the second quarter should provide additional growth moving forward.

本季度，我們的生物相似藥也實現了強勁成長，這印證了我們致力於為全球醫療保健系統創造價值的承諾。在美國以外地區，我們的銷量成長了22%，尤其令人鼓舞的是，我們在亞太地區取得了進展，第二季兩項重要的藥物獲準有望推動該地區未來的成長。

In China, our partner, BeiGene, secured approval for KYPROLIS, which joins BLINCYTO and XGEVA in our oncology collaboration there. And in Japan, the approval of Aimovig for migraine marks another important milestone for us in that market. In the U.S., we're excited by the strong launch of LUMAKRAS, which is providing hope to lung cancer patients in need of new treatment options. We're very pleased with the enthusiasm LUMAKRAS has generated in the oncology community.

在中國，我們的合作夥伴百濟神（BeiGene）的KYPROLIS獲得了批准，加入了我們在中國的腫瘤領域合作，與BLINCYTO和XGEVA共同推進。在日本，Aimovig獲準用於治療偏頭痛，這標誌著我們在日本市場又邁出了重要的一步。在美國，LUMAKRAS的強勁上市令我們倍感振奮，它為亟需新治療方案的肺癌患者帶來了希望。 LUMAKRAS在腫瘤學界引發的熱烈反響令我們非常滿意。

We're also excited that the FDA granted priority review to tezepelumab, further confirming our belief that it offers significant advantages over currently available treatment alternatives for people with severe asthma, a debilitating disease that affects millions worldwide.

我們也很高興 FDA 授予 tezepelumab 優先審查權，這進一步證實了我們的觀點，即對於患有嚴重哮喘（一種影響全球數百萬人的衰弱性疾病）的人來說，它比目前可用的治療方案具有顯著優勢。

We've long sought to complement our internal innovation efforts with the best available external innovation. And in the first half of this year, we've executed on several compelling business development transactions, which fits squarely in our stated areas of interest.

我們一直致力於將內部創新與最佳的外部創新結合。今年上半年，我們完成了幾項引人注目的業務拓展交易，這些交易與我們既定的發展方向完全契合。

The acquisition of Five Prime Therapeutics and our partnership with Kyowa Kirin, for example, have added 2 potential first-in-class Phase III-ready assets in cancer and inflammation, 2 therapeutic categories where there remains high unmet need.

例如，收購 Five Prime Therapeutics 以及與 Kyowa Kirin 的合作，為我們增加了 2 個潛在的首創 III 期臨床試驗準備就緒的癌症和發炎治療資產，這兩個治療領域仍存在著很高的未滿足需求。

The acquisition of Teneobio, which Dave will address in a moment, will significantly strengthen our protein engineering capabilities across therapeutic areas. Our strong balance sheet and cash flows will enable us to take advantage of additional business development opportunities like these as they arise.

戴夫稍後會詳細介紹對Teneobio的收購，此次收購將顯著增強我們在各個治療領域的蛋白質工程能力。我們穩健的資產負債表和充裕的現金流將使我們能夠抓住更多類似的業務發展機會。

All the work we do is focused on advancing our mission to serve patients and to do so in a way that helps to address the many challenges facing society. You may have seen our recently announced plans to invest approximately $1 billion to build 2 new manufacturing facilities, 1 in North Carolina and the other in Ohio, to meet the demand for our medicines. Both facilities will utilize cutting-edge technologies to be much more efficient and environmentally friendly than traditional plants, supporting our goal of achieving carbon neutrality by 2027. Both plants will also draw from very diverse talent pools as we, along with a number of other large companies that are part of the OneTen Coalition, look to collectively hire 1 million black Americans into well-paying jobs over the next 10 years. You can learn more about our commitment to good corporate citizenship by reading our ESG report, which can be found in the responsibility section of amgen.com.

我們所做的一切都圍繞著推進服務患者的使命，並致力於以有助於應對社會面臨的許多挑戰的方式開展工作。您可能已經了解到我們近期宣布的計劃，即投資約10億美元在北卡羅來納州和俄亥俄州各新建一座生產設施，以滿足市場對我們藥品的需求。這兩座設施都將採用尖端技術，比傳統工廠更有效率環保，助力我們實現2027年碳中和的目標。此外，這兩座工廠也將吸收多元化的人才，因為我們將與OneTen聯盟的其他幾家大型企業攜手，在未來十年內共同為100萬名非裔美國人提供高薪就業機會。您可以透過閱讀我們的ESG報告了解更多關於我們履行企業公民責任的信息，該報告可在amgen.com網站的「責任」欄位中找到。

Finally, before I turn things over to Murdo, let me thank my Amgen colleagues for their continued commitment to serving patients around the world and delivering strong performance across all aspects of our business.

最後，在將發言權交給默多之前，請允許我感謝安進的同事們，感謝他們一直以來致力於服務世界各地的患者，並在我們業務的各個方面都取得了優異的成績。

Murdo, over to you.

Murdo，該你了。

Thank you, Bob. Second quarter product sales increased 3% year-over-year. Volumes increased 8% driven by double-digit growth across a number of our products, including Prolia, Repatha and our biosimilar products MVASI and KANJINTI. Our ex-U.S. business grew 18%, with volume growth of 22% year-over-year.

謝謝鮑勃。第二季產品銷售額年增3%。銷售成長8%，主要得益於多款產品達到兩位數成長，包括Prolia、Repatha以及我們的生物相似藥MVASI和KANJINTI。美國以外的業務成長18%，銷量較去年同期成長22%。

We continue to see gradual recovery from the impacts of the COVID-19 pandemic in Q2 when compared to Q1 2021. Patient visits and lab test procedure trends continue to improve but remain below pre-COVID-19 levels. We remain focused on customer execution. Overall, U.S. field activity improved quarter-over-quarter, reaching 80% of pre-COVID levels. Face-to-face customer interactions are increasing and accounted for 60% of activity during the second quarter.

與2021年第一季相比，我們持續看到新冠疫情的影響在第二季逐步消退。患者就診量和實驗室檢測流程的趨勢持續改善，但仍低於疫情前的水平。我們將繼續專注於提升客戶服務水準。整體而言，美國地區的現場活動較上季有所改善，已恢復至疫情前水準的80%。面對面的客戶互動日益增多，佔第二季業務活動的60%。

Over the course of the pandemic, the cumulative decline in diagnoses has suppressed the volume of new patients starting treatment, which we expect will continue to impact our business during the second half of the year.

在疫情期間，確診病例的累積下降抑制了開始接受治療的新患者數量，我們預計這將在今年下半年繼續影響我們的業務。

Now let me review some product details, beginning with our innovative portfolio. In bone health, Prolia increased 24% year-over-year, driven primarily by volume growth. In the second quarter, osteoporosis diagnosis rates remained at approximately 90% of prepandemic levels. We remain focused on driving patient growth and are optimistic about Prolia's strength in the second half of the year.

現在讓我來詳細介紹一下我們的產品，首先是我們的創新產品組合。在骨骼健康領域，Prolia 的銷量年增了 24%，主要得益於銷量的成長。第二季度，骨質疏鬆症的診斷率維持在疫情前水準的約 90%。我們將繼續專注於推動患者數量的成長，並對 Prolia 在下半年的強勁表現充滿信心。

EVENITY sales increased 30% year-over-year driven by 32% volume growth. In the U.S., sales nearly doubled year-over-year as we saw an acceleration in demand trends driven by new and continuing patients. We believe EVENITY's unique bone-building attributes will continue to drive revenue growth.

受銷售成長32%的推動，EVENITY的銷售額年增30%。在美國，由於新舊患者的需求加速成長，銷售額較去年同期成長近一倍。我們相信，EVENITY獨特的骨骼強化功效將繼續推動營收成長。

Moving to Repatha, which has reached more than 1 million patients since launch. Repatha sales increased 43% year-over-year driven by 49% volume growth, and we maintained U.S. and global share leadership in the PCSK9 class.

接下來介紹瑞百安（Repatha），該藥自上市以來已惠及超過100萬名患者。瑞百安的銷售額年增43%，主要得益於銷售量成長49%，我們維持了在美國和全球PCSK9抑制劑類藥物市場的領先地位。

In the U.S., total volumes grew 37% year-over-year. And outside the U.S., volumes grew 66% year-over-year. The volume growth in the quarter was partially offset by lower net selling price resulting from an increase in Medicare Part D patients receiving Repatha and entering the coverage gap. Looking forward, we expect some ongoing reduction in global net selling price on a sequential basis. Overall, we're confident in our ability to grow Repatha to help more patients at risk of developing a heart attack or stroke.

在美國，總銷量較去年同期成長37%。在美國以外地區，銷量較去年同期成長66%。本季銷售成長部分被淨售價下降所抵消，淨售價下降是由於更多聯邦醫療保險D部分（Medicare Part D）患者接受瑞百安（Repatha）治療，從而進入了醫保覆蓋缺口。展望未來，我們預計全球淨售價將持續季減。整體而言，我們有信心擴大瑞百安的市場份額，幫助更多有心臟病或中風風險的患者。

Now on to Aimovig, which grew 24% quarter-over-quarter. On a year-over-year basis, net sales declined 16%. Volumes grew 11% but were more than offset by lower net selling price and unfavorable changes to estimated sales deductions.

接下來是Aimovig，其季增24%。但與去年同期來看，淨銷售額下降了16%。銷量成長了11%，但被淨售價下降和銷售預估扣減的不利變化所抵消。

In the U.S., Aimovig TRx volume grew 7% year-on-year, and the brand maintained total prescription share leadership among subcutaneous CGRPs. Looking ahead, we see continued rebate pressure as oral CGRPs compete for share in the market.

在美國，Aimovig TRx 的銷量年增 7%，該品牌在皮下注射 CGRP 類藥物中保持了處方總量的領先地位。展望未來，隨著口服 CGRP 類藥物爭奪市場份額，我們預計折扣壓力將持續存在。

To date, more than 0.5 million patients worldwide have been prescribed Aimovig, and we believe Aimovig has significant potential to help many more patients suffering from chronic migraine given the clinical data that will be published soon showing Aimovig superiority versus topiramate.

迄今為止，全球已有超過 50 萬名患者服用 Aimovig，我們相信，鑑於即將公佈的臨床數據顯示 Aimovig 優於托吡酯，Aimovig 具有幫助更多慢性偏頭痛患者的巨大潛力。

Moving to our inflammation portfolio. Otezla sales were $534 million in the quarter, with 5% volume growth, more than offset by unfavorable changes to estimated sales deductions and lower net selling price. In the U.S., Otezla maintained first-line share leadership in psoriasis. New-to-brand prescription volumes grew 10% year-over-year even as patient visits to dermatologists remained 15% below prepandemic levels.

接下來談談我們的發炎產品組合。本季Otezla的銷售額為5.34億美元，銷量成長5%，但這一成長被銷售預估扣減的不利變化和淨售價下降所抵銷。在美國，Otezla在銀屑病一線治療領域保持了領先地位。儘管皮膚科醫師接診量仍比疫情前水準低15%，但新處方量年增了10%。

The number of new patients who started treatment with Otezla in Q2 was near prepandemic levels, but those gains were largely offset by a lower percentage of 90-day prescription fills and lower prescription refill rates for Otezla. We expect that pandemic recovery in the dermatology segment will progress over the coming quarters.

第二季開始接受Otezla治療的新患者人數已接近疫情前水平，但90天處方配藥率和Otezla處方續配率的下降在很大程度上抵消了這一增長。我們預計皮膚科領域的疫情後復甦將在未來幾季逐步推進。

Looking forward, we're preparing for the anticipated approval of the mild-to-moderate psoriasis indication in the U.S. later this year and for the launch of Otezla in China.

展望未來，我們正在為今年稍後在美國獲得輕度至中度銀屑病適應症的預期批准以及在中國推出 Otezla 做準備。

Enbrel sales decreased 8% year-over-year, primarily driven by lower net selling prices and unfavorable changes to estimated sales deductions. On a year-over-year basis, volumes declined 1%, supported by Enbrel's long track record of efficacy and safety.

恩利（Enbrel）的銷售額較去年同期下降8%，主要原因是淨售價降低以及銷售預估扣減額的不利變化。但銷量較去年同期下降1%，這得益於恩利長期以來在療效和安全性方面的良好記錄。

Turning to biosimilars. Q2 sales were $567 million driven by strong volume growth, which was partially offset by declines in net selling price. We continue to hold leading biosimilar shares in Europe for AMGEVITA and in the U.S. for MVASI and KANJINTI. For the remainder of the year, we expect worldwide biosimilar volume growth to be offset by declines in net selling price due to increased competition.

再來看生物類似藥。第二季銷售額為5.67億美元，主要得益於強勁的銷售成長，但部分被淨售價下降所抵銷。我們繼續持有歐洲領先的生物相似藥AMGEVITA以及美國領先的生物相似藥MVASI和KANJINTI的股份。預計今年剩餘時間裡，由於競爭加劇，全球生物相似藥的銷售成長將被淨售價下降所抵銷。

Longer term, growth for biosimilars will come from expansion of existing products in new markets and launches of additional biosimilar molecules, such as AMGEVITA in the U.S. and biosimilars for SOLIRIS, STELARA and EYLEA.

從長遠來看，生物相似藥的成長將來自現有產品在新市場的擴張以及更多生物相似藥分子的推出，例如美國的 AMGEVITA 以及 SOLIRIS、STELARA 和 EYLEA 的生物相似藥。

In oncology, Neulasta Onpro remains the preferred long-acting G-CSF, with 52% volume share in the quarter. Sales declined 18% year-over-year driven by lower net selling price and lower volume. This was partially offset by a $75 million year-over-year benefit from favorable changes in reimbursement mix.

在腫瘤治療領域，Neulasta Onpro 仍然是首選的長效粒細胞集落刺激因子 (G-CSF) 製劑，本季市佔率為 52%。受淨售價和銷量下降的影響，銷售額年減 18%。但報銷組合的有利變化帶來的 7500 萬美元同比增長部分抵消了上述影響。

Neulasta's U.S. average selling price declined 35% year-over-year and 12% quarter-over-quarter. We expect this trend will continue throughout 2021 driven by intensifying competition.

Neulasta在美國的平均售價較去年同期下降35%，較上季下降12%。我們預計，在競爭加劇的推動下，這一趨勢將在2021年持續。

KYPROLIS sales increased 11% year-over-year, primarily driven by volume growth and net selling price. Moving forward, we expect growth from KYPROLIS use in combination with CD38 antibodies, including DARZALEX and SARCLISA.

KYPROLIS 銷售額年增 11%，主要得益於銷量成長和淨售價上漲。展望未來，我們預計 KYPROLIS 與 CD38 抗體（包括 DARZALEX 和 SARCLISA）聯合使用將推動其銷售成長。

I'd like to take this opportunity to comment on our recent launch of LUMAKRAS, which is off to a strong start with unaided brand awareness increasing 20 points since launch. KRAS testing in patients with metastatic non-small cell lung cancer now stands at 70%, and 46 of the top 50 testing labs now identify KRAS G12C as actionable in their laboratories. We're very pleased with the positive reaction from the oncology community, and we'll be working closely with them to ensure access for patients who can benefit from this breakthrough medicine.

我想藉此機會談談我們近期推出的LUMAKRAS。該產品上市以來勢頭強勁，品牌知名度自上市以來已提升20個百分點。目前，轉移性非小細胞肺癌患者的KRAS檢測率已達70%，排名前50的檢測實驗室中有46家已將KRAS G12C突變識別為可指導治療的指標。我們對腫瘤學界的正面反應感到非常欣慰，並將與他們緊密合作，確保能夠從這項突破性藥物中獲益的患者都能獲得治療。

Overall, I'm pleased with our Q2 execution given the sustained impact of COVID-19 on our business. We closely monitor the course of the pandemic and its impact on patients and physician behavior during the second half of the year. We'll maintain our focus on execution to ensure our medicines continue to reach the patients they can benefit.

總體而言，考慮到新冠疫情對我們業務的持續影響，我對第二季的業績表現感到滿意。我們將密切關注疫情發展及其對病患和醫師行為的影響，並將在下半年持續關注疫情走向。我們將繼續專注於執行，以確保我們的藥品能夠繼續惠及真正需要的患者。

And with that, I will turn it over to Dave.

接下來，我將把麥克風交給戴夫。

Thanks, Murdo, and good afternoon, everyone.

謝謝你，默多，大家下午好。

We made several important advances in R&D last quarter, and I will begin with our acquisition of Teneobio, which will strengthen Amgen's leadership in developing engineered protein-based medicines to treat patients with serious illnesses. There are 3 important components to the acquisition. First, Teneobio's core antibody technology will enable the development of multispecific biologics directed against targets and a wide range of diseases across our key therapeutic areas. Teneobio's antibody platform offers capabilities complementary to our XenoMouse. It is genetically modified to express human IgG molecules comprising only a heavy chain. A small single chain antigen binding VH domains from these molecules are soluble and stable and can be easily strung together like beads on a string to generate multispecific molecules.

上個季度我們在研發方面取得了多項重要進展，首先要提到的是我們對Teneobio的收購。此次收購將鞏固安進在開發工程化蛋白藥物治療重症患者領域的領先地位。此次收購包含三個重要組成部分。首先，Teneobio的核心抗體技術將協助我們開發針對特定標靶和多種疾病的多特異性生物製劑，這些標靶和疾病涵蓋了我們的關鍵治療領域。 Teneobio的抗體平台與我們的XenoMouse平台互補。該平台經過基因改造，能夠表達僅由重鏈組成的人類IgG分子。這些分子的小型單股抗原結合VH結構域具有可溶性和穩定性，可以像串珠一樣輕鬆連接起來，產生多特異性分子。

In addition, Teneobio also brings a novel lower affinity CD3 engaging technology that complements our BiTE platform. The availability of a second CD3 engager will allow us to broaden our bispecifics capabilities and enable customization of the T-cell engaging domain, depending on the disease and target.

此外，Teneobio 還帶來了一種新型的低親和力 CD3 結合技術，可與我們的 BiTE 平台形成互補。第二種 CD3 結合劑的出現將使我們能夠擴展雙特異性抗體的功能，並根據疾病和標靶客製化 T 細胞結合域。

Finally, we are acquiring clinical and preclinical oncology programs directed against high-value targets of interest, which we specifically selected based on our own discovery efforts and target validation. These include a Phase I bispecific antibody for prostate cancer that complements acapatamab, AMG 160, also targeting PSMA, and AMG 509 targeting STEAP1, which was recently granted fast-track designation by the FDA.

最後，我們正在收購針對高價值標靶的臨床和臨床前腫瘤學項目，這些項目是我們基於自身研發成果和標靶驗證而精心挑選的。其中包括一種用於治療前列腺癌的I期雙特異性抗體，它與acapatamab（一種靶向PSMA的抗體）形成互補；以及一種靶向STEAP1的抗體AMG 509，該抗體近期已獲得FDA的快速通道資格認定。

Turning to oncology. We continue to advance LUMAKRAS registration around the globe, with regulatory reviews and progress in multiple jurisdictions, including Europe and Japan. Feedback from the medical community on the LUMAKRAS launch in the U.S. has been overwhelmingly positive, and I've heard personally from oncologists who are excited to have LUMAKRAS available and are heavily screening their patients for KRAS G12C mutations. I'm pleased to report that more than 2,000 patients have received LUMAKRAS across more than 1,000 sites and 900 investigators or treating physicians, including to our global early access programs.

轉向腫瘤學領域。我們持續推動LUMAKRAS在全球的註冊工作，在包括歐洲和日本在內的多個司法管轄區均取得了監管審查和進展。 LUMAKRAS在美國上市後，醫學界的回饋非常正面。我自己也聽到腫瘤科醫師們對LUMAKRAS的上市感到興奮，並且正在積極篩檢病患的KRAS G12C突變。我很高興地報告，已有超過2000名患者在1000多個研究中心接受了LUMAKRAS治療，這些患者由900多位研究人員或治療醫生參與，其中包括我們全球早期准入計畫的患者。

In the LUMAKRAS development program, we continue to advance our broad-based combination efforts. Initial data from our Vectibix combination in colorectal cancer have been accepted for presentation at ESMO in September and the MEK and oral EGFR combination abstracts will be submitted to a medical meeting in the fourth quarter.

在LUMAKRAS研發計畫中，我們持續推動廣泛的聯合治療研究。 Vectibix聯合療法治療大腸直腸癌的初步數據已被ESMO大會接受，將於9月在ESMO大會上發表；MEK和口服EGFR聯合療法的摘要將於第四季度提交至醫學會議。

To expand our LUMAKRAS experience with SHIP2 inhibition, along with our ongoing collaboration with Revolution Medicines, we have also entered into a collaboration with Novartis for a SHIP2 combination trial.

為了擴展我們在 SHIP2 抑制劑治療 LUMAKRAS 的經驗，以及我們與 Revolution Medicines 的持續合作，我們也與諾華公司進行了 SHIP2 聯合試驗的合作。

Updates from our monotherapy non-small cell lung cancer study, including additional biomarker analyses as well as data in patients with stable brain metastases, have been accepted for presentation at the World Congress on Lung Cancer (sic) [World Conference on Lung Cancer]. Recall that we are also investigating LUMAKRAS in patients with active brain metastases. We also plan on initiating a Phase II first-line non-small cell lung cancer study in patients with PD-L1 negative and/or STK 11 mutant tumors in the third quarter.

我們單藥治療非小細胞肺癌研究的最新進展，包括額外的生物標記分析以及腦轉移穩定患者的數據，已被世界肺癌大會（World Congress on Lung Cancer）接受發表。此外，我們也正在研究LUMAKRAS在活動性腦轉移患者的療效。我們計劃在第三季啟動一項針對PD-L1陰性和/或STK11突變型腫瘤患者的II期一線非小細胞肺癌研究。

In the bemarituzumab program, we are having good discussions with regulators on the Phase III gastric cancer development path and plan to initiate a registrational program by year-end. This will include 2 Phase III trials: one investigating utility of bemarituzumab in combination with chemotherapy; and the other evaluating the addition of bemarituzumab to chemotherapy and a checkpoint inhibitor. We are also planning a potentially pivotal Phase II study with Tarlatamab, AMG 757, our half-life extended BiTE molecule targeting DLL3 for small cell lung cancer, and we look forward to discussing next steps with regulators in the coming weeks.

在貝馬利妥單抗（bemarituzumab）計畫中，我們正與監管機構就其治療胃癌的III期臨床試驗方案進行良好的磋商，併計劃在年底前啟動註冊申請流程。流程將包括兩項III期臨床試驗：一項研究貝馬利妥單抗合併化療的療效；另一項評估貝馬利妥單抗合併化療和免疫檢查點抑制劑的療效。此外，我們還計劃開展一項可能具有關鍵意義的II期臨床試驗，研究藥物為Tarlatamab（AMG 757），這是一種半衰期延長的BiTE分子，靶向DLL3，用於治療小細胞肺癌。我們期待在未來幾週內與監管機構討論後續步驟。

I'm also pleased to report that we have completed enrollment in the castrate-resistant prostate cancer expansion cohort for acapatamab or AMG 160.

我也很高興地報告，我們已經完成了去勢抵抗性前列腺癌擴展隊列中 acapatamab 或 AMG 160 的入組。

In inflammation, continuing our leadership in dermatology, we are working closely with Kyowa Kirin to advance AMG 451, also known as KHK4083, a first-in-class OX-40 antibody into Phase III for atopic dermatitis. We look forward to the presentation of the Phase II atopic dermatitis data at the annual meeting of the European Academy of Dermatology and Venereology at the end of September as well as initiating discussions with regulators on our Phase III development plans in the coming months.

在發炎領域，我們持續保持皮膚科領域的領先地位，正與協和麒麟株式會社緊密合作，推進首創OX-40抗體AMG 451（又稱KHK4083）進入治療異位性皮膚炎的III期臨床試驗。我們期待在9月底舉行的歐洲皮膚病與性病學會年會上公佈該藥物治療異位性皮膚炎的II期臨床試驗數據，併計劃在未來幾個月內與監管機構就III期臨床試驗的開發計劃展開討論。

In addition, the FDA accepted the Otezla supplemental filing for mild-to-moderate psoriasis.

此外，FDA 也接受了 Otezla 用於治療輕度至中度乾癬的補充申請。

Finally, we and our partners, AstraZeneca, were very pleased that the FDA granted tezepelumab priority review for the treatment of asthma, reflecting significant unmet medical need.

最後，我們和我們的合作夥伴阿斯特捷利康非常高興地看到 FDA 授予 tezepelumab 治療氣喘的優先審查資格，這反映了該領域存在著巨大的未滿足醫療需求。

In closing, I would like to thank the entire organization for continuing to advance important medicines for our patients. Peter?

最後，我要感謝整個組織為推動對患者至關重要的藥物研發所做的持續努力。彼得？

Thank you, Dave, and good day, everyone. I will briefly walk through our second quarter financial results before discussing 2021 guidance.

謝謝戴夫，大家好。在討論2021年業績展望之前，我將簡要回顧我們第二季度的財務表現。

The second quarter marked another period of solid performance as we grew volumes 8%, increased investment in both internal and external innovation and delivered 4% year-over-year non-GAAP EPS growth.

第二季業績表現依然穩健，銷量成長 8%，加大了對內部和外部創新的投資，非 GAAP 每股收益年增 4%。

As stated earlier, Q2 revenues at $6.5 billion increased 5% year-over-year. Other revenues at $412 million increased 38% year-over-year, primarily driven by shipments of the COVID-19 antibody therapy to Lilly. We continue to expect full year 2021 other revenues to be in the range of $1.4 billion to $1.5 billion.

如前所述，第二季營收為65億美元，年增5%。其他收入為4.12億美元，年增38%，主要得益於向禮來公司交付新冠病毒抗體療法。我們仍預計2021年全年其他收入將在14億美元至15億美元之間。

Second quarter total non-GAAP operating expenses increased 15% year-over-year as we continue to make investments to drive growth and maximize shareholder value. We expect full year operating expenses, including approximately $200 million of operating expenses related to the Rodeo, Five Prime and Teneobio acquisitions, and also to the Kyowa Kirin collaboration on an absolute basis to increase about 6% to 7% over last year, while delivering a full year operating margin of roughly 50%.

由於我們持續進行投資以推動成長並最大化股東價值，第二季非GAAP營運總支出較去年同期成長15%。我們預計全年營運支出（包括與Rodeo、Five Prime和Teneobio收購相關的約2億美元營運支出，以及與協和麒麟合作產生的營運支出）將比去年同期成長約6%至7%，同時全年營運利潤率約為50%。

On a non-GAAP basis, cost of sales as a percent of product sales increased 4.1 percentage points on a year-over-year basis to 16.9% driven primarily by product mix, including COVID-19 antibody shipments to Lilly as well as profit share and royalties. For the full year, we continue to expect cost of sales as a percent of product sales to be 16% to 17%. Our cost of sales has increased as products with royalties and product share -- profit share payments have increased.

以非GAAP準則計算，銷售成本佔產品銷售額的百分比年上升4.1個百分點至16.9%，主要受產品組合變化的影響，包括向禮來公司交付的COVID-19抗體產品以及利潤分成和特許權使用費。我們預計全年銷售成本佔產品銷售額的百分比仍為16%至17%。銷售成本的上升是由於包含特許權使用費和產品分成（利潤分成）支付的產品數量增加所致。

As a reminder, a few of our products subject to royalties, our Aimovig and biosimilars, such as MVASI, RIABNI and KANJINTI. Those subject to profit sharing arrangements are EVENITY and tezepelumab upon approval and launch.

再次提醒，我們部分產品需支付專利費，包括Aimovig及其生物相似藥，例如MVASI、RIABNI和KANJINTI。 EVENITY和tezepelumab在核准上市後將採用利潤分成模式。

Non-GAAP R&D spend increased 11% year-over-year due to investments in bema, acquired in Q2 as part of the Five Prime acquisition, and increased investments in discovery research. For the full year, we continue to expect non-GAAP R&D spend will increase as we progress our innovative early and late-stage pipeline programs. For the full year, we expect non-GAAP SG&A spend to decline.

由於對第二季度透過收購 Five Prime 獲得的 bema 公司的投資，以及對探索性研究投入的增加，非 GAAP 研發支出年增 11%。我們預計，隨著我們創新早期和後期研發管線專案的推進，全年非 GAAP 研發支出將持續成長。全年非 GAAP 銷售、管理及行政費用支出預計將下降。

Non-GAAP other income and expenses were favorable by $146 million on a year-over-year basis due primarily to our portion of BeiGene's results, which we record one quarter in arrears. Q1 BeiGene results reflect the upfront payment BeiGene received in connection with the collaboration agreement. We expect our Q3 and Q4 non-GAAP other income and expense to be more in range with our Q1 and expect full year net expense in the range of $1.3 billion to $1.5 billion.

由於我們應計入百濟神州的部分業績（該部分業績我們延遲一個季度確認），非GAAP其他收入和支出同比增加1.46億美元。百濟神州第一季業績反映了百濟神州根據合作協議收到的預付款。我們預計第三季和第四季非GAAP其他收入和支出將與第一季基本持平，全年淨支出預計在13億美元至15億美元之間。

Now turning to the outlook for the business for 2021. We are excited by our pipeline. This innovation is augmented and balanced by the business development that we have announced this year. Based on underlying market dynamics and our investment plans, we are reaffirming our 2020 revenue guidance range of $25.8 billion to $26.6 billion and our non-GAAP EPS guidance range of $16 to $17, notwithstanding absorbing the roughly $200 million of operating expenses mentioned above related to business development activities, including Five Prime, Rodeo, Teneobio and the Kyowa Kirin collaboration. These ranges reflect uncertainty continuing in the second half of the year related to emerging variants. Patient visits and lab test procedure trends in the United States continue to improve but still remain below pre-COVID-19 levels.

現在展望2021年的業務前景。我們對產品線充滿信心。今年我們宣布的業務拓展計劃進一步增強並平衡了創新。基於市場基本面和我們的投資計劃，我們重申2020年營收預期為258億美元至266億美元，非GAAP每股收益預期為16美元至17美元。儘管上述與業務拓展活動相關的營運支出約為2億美元（如上所述），包括Five Prime、Rodeo、Teneobio以及與協和麒麟的合作項目，但我們仍維持2020年營收預期不變。這些預期反映了下半年新出現的變異株所帶來的不確定性。美國的患者就診量和實驗室檢測量持續改善，但仍低於新冠疫情前的水平。

Our non-GAAP tax rate guidance remains unchanged at 13.5% to 14.5%. Our capital expenditure guidance remains unchanged at $900 million, and our capital expenditures continue to reflect our investments in our manufacturing and related facilities, including improving their environmental footprints, investments in digital technologies throughout our business and increasing ESG investments.

我們的非GAAP稅率預期維持在13.5%至14.5%不變。我們的資本支出預期也維持在9億美元不變，我們的資本支出將繼續反映我們對製造及相關設施的投資，包括改善其環境足跡、投資於我們業務中的數位化技術以及增加ESG投資。

We expect share repurchases for 2021 to be in the upper range of $3 billion to $5 billion.

我們預計 2021 年的股票回購金額將在 30 億至 50 億美元之間。

This concludes the financial update. I'll turn it over to Bob for Q&A.

財務報告到此結束。接下來交給鮑伯回答問題。

Okay. Erica, let's open the lines for questions. Maybe you could remind our callers the procedure and our desire for them to ask one question so that we have the opportunity to get to everybody who has a desire to ask a question of us. And I feel sure our callers would like to know that it's Arvind's birthday today. So bear that in mind when you ask questions of us here this afternoon. Okay, Erica, open them up.

好的，艾麗卡，我們現在開始接受提問。或許你可以提醒一下各位來電者，我們希望每位來電者只提一個問題，這樣我們才能有機會回答到所有想問問題的人。我相信各位來電者也想知道今天是阿文德的生日。所以，今天下午提問的時候請記住這一點。好的，艾莉卡，開始提問吧。

(Operator Instructions) And your first question is from Yaron Werber with Cowen and Company.

（操作說明）您的第一個問題來自 Cowen and Company 的 Yaron Werber。

This is Gabe on for Yaron, and congratulations on the quarter. My question is focused on the LUMAKRAS study in first-line lung cancer in patients with low PD-L1 and/or STK11. Could you just kind of talk about the -- I guess, your benchmarks for historical comparisons in the STK11 and G12C co-mutants and what you would use as your reference there? And any updates on your discussions with regulators in the past? You mentioned that there could be a need for head-to-head studies in the future and what those could look like, what the comparison arms would be.

我是 Gabe，替 Yaron 發言，恭喜您本季取得佳績。我的問題是關於 LUMAKRAS 在第一線治療低 PD-L1 和/或 STK11 表達肺癌患者中的應用。您能否談談—我想，您在 STK11 和 G12C 共突變體中用於歷史比較的基準是什麼？您會以什麼作為參考？您之前與監管機構的討論有什麼最新進展嗎？您提到未來可能需要進行頭對頭研究，以及這些研究可能的形式和比較組。

Yes. Thanks, Gabe. Yes. So as we mentioned, as you pointed out, this study in first-line non-small cell lung cancer will be conducted in patients who are either a PD-L1 negative or STK11 mutant. These are populations of patients, of course, who -- of patients who don't typically benefit from checkpoint inhibitors where there's really, we think, a lot of residual unmet medical need. In fact, STK11 mutational status may help confer resistance to checkpoint inhibition. So that is the population that we're targeting.

是的，謝謝，Gabe。是的。正如我們之前提到的，正如您所指出的，這項針對第一線非小細胞肺癌的研究將在PD-L1陰性或STK11突變的患者中進行。當然，這些患者群體通常無法從免疫檢查點抑制劑中獲益，我們認為，這方面存在著許多尚未滿足的醫療需求。事實上，STK11突變狀態可能有助於產生對免疫檢查點抑制劑的抗藥性。所以，這就是我們研究的目標族群。

Whether this can be potentially registration-enabling or not, I think it's too early to speculate. The FDA has generally been clear that in first-line lung cancer, they wish to see randomized trials. So one would have to anticipate having a pretty spectacular efficacy readout to lead to registration based on a single-arm Phase II trial. Obviously, if we saw compelling data, we would have the appropriate conversations going forward.

至於這是否可能有助於註冊，我認為現在下結論還為時過早。 FDA 一貫明確表示，在肺癌一線治療領域，他們希望看到隨機對照試驗。因此，如果僅憑單臂 II 期試驗就能獲得註冊，就必須預期獲得非常顯著的療效數據。當然，如果我們看到了令人信服的數據，我們會就此展開後續討論。

Your next question is from Umer Raffat with Evercore ISI.

您的下一個問題來自 Evercore ISI 的 Umer Raffat。

I just really wanted to focus on Arvind's age today.

我今天只想重點說阿文德的年齡。

You and me both. All right. What can we do for you?

你我都是。好的。我們能為您做些什麼？

Congratulations. My question today was on KRAS and really around whether there's any -- a, if you could just remind us what the plan for the interim is for the ongoing Phase III study as well as whether there's any primary analysis limited to PD-L1 negative subset in particular. I'm quite intrigued that the first-line Phase II trial is limited to PD-L1 negative or STK11.

恭喜。我今天的問題是關於KRAS的，主要是想問一下，能否請您提醒一下正在進行的III期研究的中期計劃是什麼，以及是否有專門針對PD-L1陰性亞組的主要分析？我對第一線II期試驗僅限於PD-L1陰性或STK11陽性患者這一點很感興趣。

Yes. In terms of the Phase III trial, I think the best way to think about that, Umer, is that we expect data in the first half of next year. And given the general rapidity of progression of patients historically in second and third-line lung cancer to standard therapy, the utility of an interim analysis may not be particularly useful, meaning the primary analysis often falls very quickly after an interim analysis. So of course, we'll take a look at that to get a better sense in the second half of the year of the event rates, but I would really point to the primary analysis in the first half of next year as the major event.

是的。關於第三期臨床試驗，Umer，我認為最好的理解方式是，我們預計明年上半年會獲得數據。考慮到既往二線和三線肺癌患者對標準療法的進展速度通常很快，中期分析的意義可能不大，這意味著主要分析通常會在中期分析之後很快進行。所以，我們當然會在下半年專注於中期分析，以便更了解事件發生率，但我認為明年上半年的主要分析才是最重要的。

And then in first line, as I said, the -- we think that there is significant unmet medical need in the PD-L1 negative, STK11 mutant and/or STK11 mutant population given the relative refractoriness of those tumors to currently available treatments. And so we're very much looking forward to getting that study launch shortly and seeing the data readout. We'll provide guidance on time lines as soon as enrollment is really underway.

正如我之前所說，我們認為，鑑於PD-L1陰性、STK11突變和/或STK11⁺腫瘤對現有療法的相對抗藥性，這類族群存在顯著的未滿足醫療需求。因此，我們非常期待盡快啟動這項研究，並看到數據解讀。一旦患者招募工作真正開始，我們將立即提供時間表的指導。

Your next question is from Jay Olson with Oppenheimer.

下一個問題來自奧本海默公司的傑伊·奧爾森。

Happy birthday, Arvind. I'm curious about the combination data of LUMAKRAS with Vectibix. Will that be in colorectal cancer only? Or should we expect to see combination data in non-small cell lung cancer? And related to that, can you comment on the potential for that combination data to drive incremental use of Vectibix?

Arvind，生日快樂！我對LUMAKRAS聯合Vectibix的資料很感興趣。這些數據僅限於大腸直腸癌嗎？還是也包括非小細胞肺癌？另外，您能否談談這些合併用藥數據對Vectibix潛在用量成長的影響？

Thanks, Jay. Given the regimen that we're studying, you can expect that most of the patients that have been enrolled on that particular combination of LUMAKRAS and Vectibix will have colorectal cancer given the backbone of Vectibix here, although the trial is open across malignancies for treating physicians to enroll patients if they feel that regimen may be appropriate.

謝謝，傑伊。鑑於我們正在研究的治療方案，您可以預期，大多數接受LUMAKRAS和Vectibix聯合治療的患者都將患有結直腸癌，因為Vectibix是該療法的核心藥物。不過，該試驗也對所有惡性腫瘤患者開放，治療醫師如果認為該方案可能合適，即可招募患者。

In terms of driving the uptake of Vectibix, I don't want to speculate on that. Our job here is really to generate these combination data and see if we think we can really drive things forward, particularly in colorectal cancer.

至於如何推動Vectibix的普及，我不想妄加猜測。我們目前的工作重點是收集聯合用藥數據，看看我們是否真的能夠推動Vectibix的推廣，尤其是在大腸直腸癌領域。

Your next question is from Salim Syed with Mizuho.

您的下一個問題來自瑞穗銀行的 Salim Syed。

And I'll add my happy birthday, Arvind. Me and you, we're both 30. So I just wanted to focus on the tax petition, if I can. So it seems like this notice of deficiency was not just for 1 year, but it was for 3 years, 2010, 2011 and 2012. So I'm just curious if there's pattern here and how you guys are doing the accounting and is triggering these notice of deficiencies? And I guess the underlying question here, should we be expecting a notice of deficiency or ease for 2013 through '20? And then just curious what the interest rate is that the IRS would impose here.

祝你生日快樂，Arvind。你我都30歲了。所以，如果可以的話，我想重點談談稅務申訴。看起來這份欠稅通知書並非只針對一年，而是針對三年，分別是2010年、2011年和2012年。所以我很好奇這其中是否存在某種規律，以及你們是如何進行會計核算並觸發這些欠稅通知書的？我想，這裡最根本的問題是，我們是否應該預期在2013年至2020年期間收到欠稅通知書，或者情況會有所改善？另外，我還想知道國稅局會徵收多少利息。

Salim, thank you. It's Peter. And on your question around the IRS matter, the dispute, look, these notices are related to a transfer pricing dispute with the IRS regarding the allocation of the profits between the U.S. and the territory of Puerto Rico. So you can see we have a difference of opinion on the value of the significant risks and the complexity we undertake with activities performed at our Puerto Rico facility. We strongly believe the IRS' position is without merit, and we have appropriate tax reserves, and this dispute will take several years to resolve.

薩利姆，謝謝。我是彼得。關於你提到的國稅局相關事宜，也就是爭議，這些通知與我們和國稅局之間關於美國和波多黎各領土之間利潤分配的轉讓定價爭議有關。所以你可以看到，我們對在波多黎各工廠開展的業務活動所涉及的重大風險和複雜性存在分歧。我們堅信國稅局的立場毫無根據，我們擁有充足的稅務準備金，而且這場爭議需要數年時間才能解決。

I would like to note, Salim, that Puerto Rico is our flagship manufacturing facility, responsible for the majority of Amgen's global manufacturing. We're proud of our Puerto Rico operations, very proud of them and our colleagues there. We've had a major manufacturing presence in Puerto Rico for about 30 years. We have more than 2,200 highly skilled colleagues in Puerto Rico and who produce very sophisticated biologic medicines for patients all over the world with serious diseases. We've invested nearly $4 billion to expand and modernize those facilities in Puerto Rico, and we're proud to be consistently recognized as one of the island's best and most responsible employers.

薩利姆，我想指出，波多黎各是我們最重要的生產基地，承擔安進全球大部分的生產任務。我們為在波多黎各的業務感到自豪，也為我們在那裡的同事感到無比驕傲。我們在波多黎各擁有重要的生產基地已有近30年的歷史。我們在波多黎各擁有超過2,200名技術精湛的同事，他們為世界各地患有嚴重疾病的患者生產精密的生物製劑。我們已投資近40億美元用於擴建和現代化改造波多黎各的生產設施，並且我們很榮幸能夠一直被公認為波多黎各島上最優秀、最負責任的雇主之一。

So on the matter of interest rate, I'll have to refer you to the IRS for that. But that's the IRS matter in brief.

關於利率問題，我需要請您諮詢美國國稅局。以上就是關於國稅局相關事宜的簡要說明。

Your next question is from Terence Flynn with Goldman Sachs.

下一個問題來自高盛的 Terence Flynn。

Maybe another one for Peter. I was just wondering if you can comment on margins longer term. I noticed you called out that royalty and profit splits are going to be increasing here given some of the newer products you're launching. But how should we think about that 50% operating margin this year and the cadence on the forward?

或許可以再問彼得。我只是想問您能否談談長期利潤率。我注意到您提到，鑑於您即將推出一些新產品，版稅和利潤分成比例將會提高。但是，我們該如何看待今年50%的營業利潤率以及未來的發展節奏呢？

Terence, thank you. And as always, we don't give long-term margin guidance. But what I'd -- and I'd really like to say, our North Star around this, we always pause and think about our objective is to grow our after-tax cash flows for the enterprise versus targeting specific operating margin or OpEx growth rates. So we're going to continue to make prudent investments that lead to that objective. So I would just note, we're continuing to invest in internal and external innovation. You've seen the fruits of that in the second quarter, the launches of new products, broader digitalization efforts.

特倫斯，謝謝。像往常一樣，我們不提供長期利潤率指引。但我想強調的是，我們始終秉持著一個核心原則：我們的目標是提升企業稅後現金流，而不是追求特定的營業利潤率或營運支出成長率。因此，我們將繼續進行審慎的投資，以實現這一目標。我想指出的是，我們正在持續投資於內部和外部創新。您已經在第二季看到了這些投資的成果，例如新產品的推出和更廣泛的數位化措施。

Secondly, we highlighted our expectation that R&D expenses are going to grow year-over-year as we increase our spend on AMG 160 and 757 in dose expansion. We're going to rapidly advance those assets in prostate and small cell lung cancer. We have 3 biosimilars in Phase III, 3 inflam assets in Phase II.

其次，我們強調，隨著我們在AMG 160和757劑量擴展方面的投入增加，我們預計研發費用將逐年增加。我們將加速推動這些藥物在攝護腺癌和小細胞肺癌領域的研發。目前我們有3個生物相似藥處於III期臨床試驗階段，3個發炎相關藥物處於II期臨床試驗階段。

Third, I'll just note, Terence, that we're absorbing the upfront costs related to the acquisition of Rodeo as well as the cost of the Five Prime acquisition, our recent collaboration with Kyowa Kirin and our recently announced acquisition of Teneobio, which we do expect to close in the second half of 2021.

第三，特倫斯，我只想指出，我們正在承擔收購 Rodeo 的前期成本，以及收購 Five Prime 的成本、我們最近與 Kyowa Kirin 的合作，以及我們最近宣布的對 Teneobio 的收購，我們預計該收購將在 2021 年下半年完成。

We also plan to rapidly progress these Phase III-ready molecules in development of bema and KHK4083. We began seeing higher manufacturing costs in Q2. Those were related to the Lilly COVID antibody efforts, and that adds to the OpEx build for the rest of the year, too. But on a year-over-year basis, remember, we're comparing a depressed spend in Q2 and Q3 2020 due to COVID. So at the end of the day, there's any number of financial metrics that we expect to be measured on by our investors and the analysts. And we take pride in knowing that we want to end up really in the top of the group in terms of our operating efficiency. So that's very important to us. So you can rest assured that we'll continue to stay focused on that.

我們也計劃加快推進bema和KHK4083的III期臨床試驗。第二季度，我們的生產成本開始上升。這與禮來公司的新冠抗體研發工作有關，也增加了今年剩餘時間的營運支出。但要注意的是，由於新冠疫情的影響，2020年第二季和第三季的支出都處於較低水準。最終，投資人和分析師會根據一系列財務指標來評估我們的業績。我們引以為傲的是，我們希望在營運效率方面能夠名列前茅。這對我們至關重要。您可以放心，我們將繼續專注於此。

Your next question is from Matthew Harrison with Morgan Stanley.

下一個問題來自摩根士丹利的馬修·哈里森。

Dave, I was wondering if you could just comment on the IL-2 mutein. I know we're going to see some of the data here for SLE towards the end of the year, but it looks like you started a Phase II, and you're also looking at UC. Just maybe broadly on the profile and what you think you need to generate out of Phase IIb to have that be a competitive asset.

Dave，我想請你談談IL-2突變體。我知道年底我們會看到一些關於系統性紅斑狼瘡（SLE）的數據，但看起來你們已經啟動了II期臨床試驗，而且你們也在研究潰瘍性結腸炎（UC）。我想請你大致談談它的特性，以及你認為需要從IIb期臨床試驗中獲得哪些數據才能使其成為具有競爭力的藥物。

Yes. Thanks, Matt. And I'm glad you brought up AMG 592, our IL-2 mutein. Just to remind everyone, this is a molecule designed to enhance the number and function of T regulatory cells, some of the key modulatory cells in the immune system. In many autoimmune diseases, the T regulatory axis is out of whack.

是的，謝謝你，馬特。很高興你提到了AMG 592，也就是我們的IL-2突變體。提醒大家一下，這是一種旨在增強T調節細胞數量和功能的分子，T調節細胞是免疫系統中一些關鍵的調節細胞。在許多自體免疫疾病中，T調節軸都處於失衡狀態。

As you mentioned, we anticipate sharing Phase Ib data in lupus at a medical meeting towards the end of the year, and we look forward to being able to share those data with you. In addition, a Phase II trial in lupus is actively enrolling now. And then finally, as you mentioned, Matt, we are launching a study in ulcerative colitis, another autoimmune disorder in which there's quite a bit of evidence of dysregulation of the T reg axis. So I think it's really the Phase II readouts here that will be critical as we accrue those data. As always, we'll look to make sure that we are adding something to what is standardly available.

正如您所提到的，我們預計將在年底的醫學會議上分享狼瘡Ib期臨床試驗數據，並期待與您分享這些數據。此外，一項狼瘡II期臨床試驗目前正積極招募病患。最後，正如您所提到的，Matt，我們正在啟動一項潰瘍性結腸炎的研究，潰瘍性結腸炎是另一種自體免疫疾病，有大量證據表明其存在Treg軸功能紊亂。因此，我認為II期臨床試驗的結果至關重要，因為我們將持續累積這些數據。我們將一如既往地努力，確保我們的研究成果能為現有標準療法增添新的內容。

In lupus, there remains very large residual unmet medical need. There was an approval within the last day or 2, of course, but only the second drug in 40 years and a very large patient population there still requiring active medicines. Ulcerative colitis, particularly for long-term remission, is also an area with substantial unmet medical need. So it's full speed ahead in the IL-2 mutein program, and we'll look forward to sharing these data with you.

在狼瘡領域，仍存在巨大的未滿足醫療需求。當然，就在最近一兩天，一種新藥獲批上市，但這卻是40年來第二種核准的藥物，而該領域仍有大量患者需要有效的治療藥物。潰瘍性結腸炎，尤其是長期緩解方面，也存在著巨大的未滿足醫療需求。因此，IL-2突變體計畫正在全力推進，我們期待與您分享這些數據。

Your next question is from Geoff Meacham with Bank of America.

下一個問題來自美國銀行的傑夫‧米查姆。

Happy birthday, Arvind. Commercial question on Otezla for Murdo. So when you look at the growth in the first half of this year, how much of a factor was COVID versus, say, competition or pricing? And do you think any of these headwinds could impact the upcoming launch when you look at the mild-to-moderate disease population?

Arvind，生日快樂！關於Otezla，我有個商業方面的問題想請教Murdo。今年上半年的成長中，新冠疫情的影響有多大？相較之下，競爭或定​​價等因素又佔多大比重？考慮到輕度至中度新冠患者群體，您認為這些不利因素會對即將上市的產品產生影響嗎？

Yes. Thanks, Geoff. I would say throughout the course of last year, we saw a slowdown in the number of bio naive psoriasis patients moving into the market just based on COVID disruption to patient visits. And given that Otezla is an early option in the treatment of psoriasis, we were impacted by that, I would say, more than the biologics, which tend to gain growth from Otezla and from each other. So that slowdown in the new patient diagnosis last year compounds into our growth rate this year. The good news on quarter is we saw new patient trends tick up. So we did see 10% growth in new patient -- new-to-brand prescriptions in the quarter. However, this was somewhat offset by an increase in the number of patients that switched away from Otezla to another treatment. And we think that, that was pent-up treatment decision-making that didn't happen because patients weren't going to see their dermatologist last year.

是的，謝謝，Geoff。我想說，去年全年，由於新冠疫情導致患者就診量減少，我們看到進入市場的生物製劑初治銀屑病患者數量有所放緩。鑑於Otezla是銀屑病治療的早期選擇，我認為我們受到的影響比生物製劑更大，因為生物製劑的增長往往依賴Otezla以及彼此之間的市場互動。因此，去年新患者診斷數量的放緩影響了我們今年的成長率。本季的好消息是，我們看到新患者數量回升。因此，本季新患者（即首次使用Otezla的患者）的處方量增加了10%。然而，這在一定程度上被從Otezla轉而使用其他療法的患者數量的增加所抵消。我們認為，這是由於患者去年無法去看皮膚科醫生，導致他們原本計劃的治療決策被擱置了。

There were some price reductions, mostly related to our co-pay programs, but that's usually a good indication of new patients starting. So overall, I would say it's primarily COVID impact. With respect to other products coming in, I'm not sure how to answer that. What I can say is we continue to like our share position. Our share has held in the share of bio naive psoriasis patients, and we continue to feel optimistic about the growth of Otezla, given the pending indication in mild-to-moderate patients, which should come, hopefully by the end of this year. Teams continue to execute well. Our field execution, as I mentioned in my opening remarks, is improving, and we're very focused on making sure we continue to grow Otezla over the long haul.

價格下調，主要與我們的共付額計劃有關，但這通常是新患者開始使用的重要指標。因此，總體而言，我認為這主要是新冠疫情的影響。至於其他即將上市的產品，我不太確定該如何回答。但我可以肯定的是，我們仍然對目前的市場份額感到滿意。我們在生物製劑初治銀屑病患者的市場份額保持穩定，並且鑑於Otezla在輕度至中度患者中的適應症正在審批中（預計在今年年底前獲批），我們對Otezla的增長前景依然保持樂觀。團隊的執行力依然強勁。正如我在開場白中提到的，我們的市場執行力正在不斷提升，我們將全力確保Otezla的長期持續成長。

Your next question is from Ronny Gal with Bernstein.

下一個問題來自伯恩斯坦的羅尼·加爾。

Let's start with the immunology theme here. You guys are developing both STELARA and HUMIRA for 2023, 2024's biosimilars. And given you're going to be in both sides of the innovator of biosimilar world, I was wondering if you had a thought about kind of like the long-term trajectory of pricing in the immunology market that is without giving specific numbers? Do you kind of -- should we begin to see something along the lines of what we see with diabetes with an ongoing gradual price decreases? So like how do you think about this market longer term?

我們先從免疫學這個話題談起。你們正在研發STELARA和HUMIRA，計劃在2023年和2024年上市。鑑於你們將同時涉足生物相似藥創新者和開發者這兩個領域，我想請教一下，你們對免疫學市場的長期定價走勢有什麼看法？ （這裡不涉及具體數字。）你們認為免疫學藥物的價格走勢會像糖尿病藥物一樣持續逐步下降嗎？你們是如何看待這個市場的長期發展的？

Great. Murdo, do you want to answer Ronny?

太好了。默多，你想回答羅尼的問題嗎？

Sure. Thanks for the question, Ronny. I'm hesitant to go out too far. What we are seeing, of course, in inflammation right now is a lot of new entrants, a lot of new mechanisms and a lot of competition, which is increasing the gross to nets that new entrants have to pay to secure access. We're also seeing increased management by the large national PBMs of national formularies as to which mechanisms get placed in a preferred status versus being held in reserve after patients fail in earlier lines of therapy. So if we take rheumatoid arthritis for -- as an example, I do see TNFs continuing to entrench themselves in that first-line position and novel mechanisms are likely to be in second and perhaps even third line after patients have failed to have resolution of their RA symptoms or improve their -- the progression of their disease.

當然。謝謝你的提問，羅尼。我不太想妄下斷言。目前，發炎領域湧現大量新藥，新的治療機制層出不窮，競爭也異常激烈，這導致新藥上市成本（毛利/淨利比）不斷攀升，以確保藥物的市場准入。此外，大型國家藥品福利管理機構（PBM）和國家藥品目錄也加強了對藥物機制的管理，決定哪些機制應該優先使用，哪些機制應該在患者早期治療失敗後作為替代方案。以類風濕性關節炎為例，我認為TNF抑制劑將繼續鞏固其第一線治療的地位，而新的治療機轉則可能在患者類風濕性關節炎症狀緩解或病情進展減緩後，才會作為二線甚至三線治療方案。

In the biosimilar dynamics, I think we're seeing now the increase in interest from both payers and PBMs and providers given some of the trends that we're seeing with the early biosimilars in the inflammation category. And I do think that interest in biosimilars will increase, and I think that biosimilar penetration of parent molecule or originator molecule will accelerate with new entrants. So we're expecting that to be the condition on the ground by the time we launch AMGEVITA in the U.S.

在生物相似藥領域，鑑於早期生物相似藥在發炎治療方面的一些發展趨勢，我認為目前支付方、藥品福利管理機構 (PBM) 和醫療服務提供者對生物相似藥的興趣都在不斷增長。我確實認為，人們對生物相似藥的興趣將會持續成長，隨著新藥的出現，生物相似藥對原廠藥的滲透率將會加速。因此，我們預計，到 AMGEVITA 在美國上市時，市場情況將會如此。

But overall, I would just come back to the strength that we have as a company given our portfolio of innovator and originator molecules enhanced with the presence of our biosimilar portfolio. And I think that affords us an opportunity to serve many patients across a host of autoimmune diseases as well as serve providers, payers and PBMs with a lot of value to deliver to the health care system.

但總的來說，我認為我們公司最大的優勢在於我們擁有豐富的創新藥和原廠藥產品組合，再加上生物相似藥產品組合，這使我們能夠更好地服務於眾多自體免疫疾病患者，同時也能為醫療服務提供者、支付方和藥品福利管理機構（PBM）帶來巨大的價值，從而惠及整個醫療保健系統。

Your next question is from Geoffrey Porges with SVB Leerink.

您的下一個問題來自 SVB Leerink 的 Geoffrey Porges。

I'll continue with the biosimilar vein, specifically on denosumab. What are you thinking in terms of the first biosimilar coming in for denosumab? And then would you expect the erosion trajectory for branded Prolia and XGEVA to be similar to, for example, Neulasta or to the erosion of the oncology biologics? Or would you expect it to be more gradual or fast? Just wondering what you think the trajectory will look like.

我將繼續探討生物相似藥，特別是地諾單抗。您對首個上市的地諾單抗生物相似藥有何看法？您認為原廠藥Prolia和XGEVA的市佔率下降軌跡會與Neulasta或其他腫瘤生物製劑類似嗎？還是會更緩慢或更快？我只是想知道您對市場趨勢的看法。

Thanks, Geoffrey, for the question. I would say it's, again, hard to project into the future as to how health care systems, payers and providers will change in their adoption of biosimilars. But I think given that denosumab is a Part B product, the oncology biosimilar curves would be a close approximation of what we've been planning for.

謝謝Geoffrey的提問。我想再次強調，很難預測未來醫療保健系統、支付方和醫療服務提供者在生物相似藥的採用方面會發生怎樣的變化。但考慮到地諾單抗是B部分藥品，我認為腫瘤生物相似藥的曲線應該與我們先前的規劃非常接近。

Your next question is from Michael Yee with Jefferies.

下一個問題來自傑富瑞集團的麥可葉。

We had a 2 parter for David. On KRAS, you have upcoming data for MEK plus or minus EGFR. And just wanted to understand in the context for how to interpret that data, what is good data? And is the goal to significantly increase response rate in PFS beyond LUMAKRAS alone? Maybe just help us rightsize how to think about that study.

我們之前給David安排了兩個部分。關於KRAS，你們即將公佈MEK聯合或不合併EGFR的數據。我想了解一下，在解讀這些數據時，什麼樣的數據才算有效？研究目標是否為顯著提高PFS的緩解率，使其超過LUMAKRAS單藥治療？或許您能幫我們更理解這項研究。

And you also announced that you expanded a combination with the Novartis SHIP2. Is that just diversifying and spreading it around? Or how to think about SHIP2 if you have done a second collaboration there?

您也宣布擴大了與諾華SHIP2的聯合用藥。這只是多元化和推廣嗎？或者，如果您已經與SHIP2進行了第二次合作，您應該如何看待SHIP2呢？

Yes. Thanks, Mike. Let me start with the second part first. You're exactly right. That's simply diversifying our experience. We're moving forward, as I noted, with both Revolution Medicines combination as well as this new collaboration with Novartis, and we'll look forward to both data sets.

是的，謝謝，麥克。我先從第二部說起。你說得完全正確。這只是豐富我們的經驗。正如我之前提到的，我們正在推進與Revolution Medicines的聯合療法以及與諾華的這項新合作，我們期待這兩組數據的公佈。

In terms of the MEK or EGFR combinations, as I've said before, in terms of response rate, it's going to vary by line of therapy and indication in terms of what sort of increments that you want to see. But generally, 10%, 20%, 30% relative improvement in response rates and progression-free survival certainly beyond first-line is typically what we would want to see. And those are the rough sort of benchmarks that we'll use.

關於MEK或EGFR合併療法，如我之前所說，就緩解率而言，不同的治療線數和適應症會帶來不同的效果提升幅度。但一般來說，我們希望在初始治療的基礎上，緩解率和無惡化存活期能夠提高10%、20%甚至30%。這些是我們大致的評估基準。

Now on these first cohorts, of course, the critical thing upfront is safety and determining appropriate doses and then moving into expansion cohorts for efficacy. Thanks again.

當然，對於首批受試者而言，最關鍵的是安全性，需要確定合適的劑量，然後再進入擴展隊列以評估療效。再次感謝。

Your next question is from Alethia Young with Cantor Fitzgerald.

你的下一個問題來自坎托·菲茨杰拉德的阿萊西亞·楊。

Happy birthday to one of the best in the IR games. Cheers to you, Arvind. I wanted to get a little bit of flavor on the Repatha. And I know you're seeing very nice volume growth, but like continued kind of pricing pressure or discounting pressure. Do you think we're kind of hitting a stabilization point? I know you talked about a little bit of sequential acceleration, but just if you can give us some flavor on how to think about when that might start to rightsize and stabilize and see real growth from the volume that you're generating?

祝投資者關係領域最優秀的人之一生日快樂！ Arvind，乾杯！我想了解一下Repatha的情況。我知道你們的銷售成長非常可觀，但同時也面臨持續的價格壓力或折扣壓力。你認為我們是否已經接近穩定點了？我知道你之前提到過銷量會略有加速成長，但你能否具體談談，我們該如何判斷銷售何時才能真正開始趨於穩定，並實現真正的成長？

Yes. Thanks, Alethia. We're quite happy with the performance of Repatha and its ability now to really treat a large number of patients. We've reached 1 million patients now with Repatha. So quite a milestone.

是的，謝謝，阿萊西亞。我們對瑞百安（Repatha）的療效非常滿意，它現在能夠真正治療大量的病人。我們已經用瑞百安治療了100萬名患者，這是一個非常重要的里程碑。

The overall dynamic that is dragging price down is really a U.S. Part D patient dynamic as patients enter into the coverage gap or as we sometimes refer to, the doughnut hole. And as we expand our percentage or share of business in the Part D or Medicare Part D business and segment of the market, we will see some net negative price drag quarter-over-quarter. Now it's not going to be as precipitous as the price changes that we've made historically. So our volume's outpacing that, and we will see that drop to the net sales line. So overall good evolution.

導致價格整體下降的主要因素是美國D部分健保患者的投保情況，因為患者會進入健保覆蓋缺口，也就是我們常說的「甜甜圈漏洞」。隨著我們在D部分健保或Medicare D部分業務及市場份額的擴大，我們預計每季都會出現淨價格下降。不過，這種下降幅度不會像我們以往的價格調整那麼劇烈。因此，我們的銷售成長超過了價格下降的幅度，最終淨銷售額也會下降。所以，整體而言，這是一個好的發展趨勢。

We're also seeing nice growth on Repatha ex U.S. where price is relatively stable year-on-year. So that part of the mix is helping bolster price evolution over time as well. But some slight drag will continue. But again, it's a good sign because it means we're expanding that Medicare pool of patients much more rapidly than we did historically.

我們也看到Repatha（除美國以外）的銷售成長良好，價格較去年同期相對穩定。因此，這部分銷售也有助於推動價格的長期成長。但價格仍會受到一些輕微的拖累。不過，這仍然是一個好兆頭，因為它意味著我們擴大Medicare患者群體的速度比以往快得多。

Your next question is from Kennen MacKay with RBC Capital Markets.

下一個問題來自加拿大皇家銀行資本市場的 Kennen MacKay。

Maybe just would love to get a perspective on which combinations you're most excited about currently for LUMAKRAS, whether it's more in line with previously with the oral and antibody MEK inhibitors or the MTOR inhibitor maybe? Or with the Novartis collaboration, does the SHIP2 now take the top seat?

我想了解一下，目前您對LUMAKRAS的哪些聯合療法最感興趣？是更傾向於之前的口服和抗體MEK抑制劑，還是MTOR抑制劑？或者，在與諾華的合作中，SHIP2是否佔據了主導地位？

And then just one quick question on the biosimilar pipeline. When do you see is the earliest that you might be able to launch your biosimilar, EYLEA, it's ABP 938? And congrats on the birthday, Arvind.

最後還有一個關於生物相似藥研發管線的問題。您認為最早什麼時候可以推出您的生物相似藥EYLEA（ABP 938）？還有，祝Arvind生日快樂。

Yes. Maybe I'll start with the question on combinations. Of course, the ones we like the best are the ones that work, and that's what we're testing right now. It would actually -- all of these combinations have been selected off for one or another reason or both. One, most importantly, biologic plausibility. So reason to believe in either additive or synergistic effects; and then two, if combining molecules are part of a background regimen. And so we think we're really covering the waterfront in terms of indications of interest with relevant combinations here.

是的。或許我可以先從藥物組合的問題談起。當然，我們最喜歡的組合就是那些有效的組合，而這正是我們目前正在測試的。實際上，所有這些組合都是出於某種原因（或兩者兼有）而篩選出來的。首先，也是最重要的，是生物學上的合理性。也就是說，我們有理由相信它們會產生疊加或協同效應；其次，如果這些組合是基礎治療方案的一部分。因此，我們認為，就相關的適應症而言，我們已經涵蓋了所有方面。

And at this point, Kennen, I think it's really an empirical matter of generating the data. And of course, I will share that as we've outlined.

肯南，我認為現在真正的問題在於如何收集資料。當然，我會按照我們之前討論的方式分享這些數據。

And Kennen, we haven't announced our timing on EYLEA, but we are moving quickly in the enrollment of that program, and we anticipate being early in the sequence of launches for that product.

Kennen，我們還沒有公佈EYLEA的上市時間，但我們正在快速推進該計畫的招生工作，並預計會率先推出該產品。

Your next question is from Carter Gould with Barclays.

下一個問題來自巴克萊銀行的卡特·古爾德。

I'll pass on my happy birthday wishes to Arvind, too. I wanted to ask on your OX-40 program. I know it's moving into Phase III next year. Just wanted to see any further color on the population or dosing you're looking to move forward with in the Phase III? And if the lingering uncertainty over the JAKs is in any way changed or, I guess, evolved your underlying assumptions around that market would be helpful.

我也會向Arvind轉達我的生日祝福。我想問一下關於你們的OX-40專案。我知道它明年將進入III期臨床試驗。我想了解你們在III期臨床試驗中計劃要研究的人群或劑量方案。另外，如果JAK抑制劑市場方面仍然存在的不確定性有所改變或發展，你們關於該市場的基本假設也請告知。

Yes. Thanks, Carter. We're very enthusiastic about this molecule. Atopic dermatitis is a disease, widespread prevalence, actually global populations. Despite existing therapies, we think there is a very large amount of residual unmet medical need. Patients often cycle through therapies given the novel mechanism of action you're targeting the OX-40 pathway, we think there is quite a big opportunity to have a real impact in this field.

是的，謝謝卡特。我們對這個分子非常感興趣。異位性皮膚炎是一種廣泛流行的疾病，實際上在全球都有患者。儘管目前已有治療方法，但我們認為仍有大量未被滿足的醫療需求。患者往往需要不斷更換治療方案。有鑑於你們針對OX-40通路這個全新作用機制，我們認為在這個領域有很大的機會產生真正的影響。

As I mentioned, we'll be presenting the Phase IIb data at the end of September at one of the major European dermatology meetings. And I think there, you'll get a sense of our thoughts on dosing and what things may look like going forward. And of course, as we have discussions with regulators, we'll outline our plans on the Phase III program, which will, in all likelihood, be a suite of studies. Let me ask Murdo to comment a little further here.

正如我之前提到的，我們將在九月底的歐洲主要皮膚病學會議上公佈IIb期臨床試驗數據。我想屆時大家就能了解我們對給藥方案的思路以及未來的發展方向。當然，在與監管機構討論的過程中，我們也會概述III期臨床試驗計劃，該計劃很可能包含一系列研究。接下來，我想請Murdo先生再補充一些內容。

Yes. And Carter, we obviously pay close attention to the JAK safety concerns as raised on the Xeljanz data and applied some reduction in JAK penetration assumptions to the AD market when we were evaluating the attractiveness of the OX-40 asset. And I think that was one of the drivers here. We -- the biologics still have a large role to play. We think, initially, the OX-40 asset will establish perhaps a second line opportunity in the market, and we can expand from there. But the portion of the market that we think will be addressed by JAKs is probably smaller than was once considered.

是的。卡特，我們顯然非常關注Xeljanz數據中提出的JAK安全性問題，並在評估OX-40資產的吸引力時，對AD市場的JAK滲透率假設進行了相應調整。我認為這是促成這次評估的因素之一。生物製劑仍扮演著重要的角色。我們認為，OX-40資產最初可能會在市場上佔據二線治療的地位，之後我們可以以此為基礎進行拓展。但我們認為JAK藥物最終能夠涵蓋的市場份額可能比之前預想的要小。

Your next is from Cory Kasimov with JPMorgan.

接下來這則訊息來自摩根大通的科里·卡西莫夫。

Most importantly, happy birthday to Arvind. Wanted to go back to the line of questioning around the LUMAKRAS combination work and ask specifically about what you're doing with PD-1s at this point and when you expect to have an update there? And is it really still just about trying to figure out the dosing currently before you move forward?

最重要的是，祝Arvind生日快樂。我想回到之前關於LUMAKRAS聯合療法的問題，具體問問您目前在PD-1抑制劑方面的研究進展，以及預計何時會有新的進展？目前是否真的還在摸索劑量方案，然後再繼續前進？

Yes. Thanks, Cory. As we've discussed before, we're looking at both direct combinations and sequential therapy here. So -- and I think you can see -- you can expect to see data from both of those sometime through the first half of next year or so as we accumulate enough data to define what the relevant path forward is with checkpoint inhibitors. So more to come there, but we continue to actively work on these development programs.

是的，謝謝，科里。正如我們之前討論過的，我們正在研究直接聯合療法和序貫療法。所以——我想您也看到了——隨著我們累積足夠的數據來確定免疫檢查點抑制劑的未來發展方向，預計在明年上半年左右，您將會看到這兩種療法的相關數據。所以，後續將會有更多資訊公佈，我們將繼續積極推動這些研發項目。

Your next question is from Chris Raymond with Piper Sandler.

下一個問題來自克里斯·雷蒙德和派珀·桑德勒。

This is Ally Bratzel on for Chris this afternoon. Just on BD, you've had a lot of activity in the oncology and inflammation space. Just any color on how you're prioritizing other areas of interest on the development side versus opportunities that bolster some of your more legacy commercial franchises like renal? And then maybe more specifically, on renal, how are you thinking about your longer-term strategy or prioritization for investing in the franchise be it through internal or external innovation?

我是Ally Bratzel，今天下午替Chris接受訪問。關於BD公司，你們在腫瘤和發炎領域動作頻頻。能否談談你們在研發方面是如何權衡其他感興趣領域和鞏固現有商業業務（例如腎臟疾病）的機會的？更具體地說，在腎臟疾病領域，你們是如何考慮長期策略或優先投資方向的，無論是內部創新還是外部創新？

Yes. So Ally, I'll just repeat what I've said many times before, which is that our business development efforts are focused in the areas where we have ongoing strong research presence and/or commercial presence. So you're right, we've been active in oncology and in the immunology area. We continue to look for opportunities in both those spaces as well as in general medicine. And to the extent that we see things that we think we can add value to in nephrology or bone health or in the migraine area, we'll look there as well. So we have active efforts underway, and we look, again, across the marketplace actively and with a focus on how we can earn a return for our shareholder -- for our shareholders from the assets that we might license or acquire.

是的。艾莉，我再重複一遍我之前說過很多次的話，那就是我們的業務拓展工作主要集中在我們擁有強大研發實力和/或商業實力的領域。你說得對，我們一直活躍在腫瘤學和免疫學領域。我們會繼續在這些領域以及一般醫學領域尋找機會。如果我們在腎臟科、骨骼健康或偏頭痛領域發現能夠創造價值的機會，我們也會關注這些領域。所以，我們正在積極開展相關工作，並且會積極地在整個市場中尋找機會，重點關注如何透過我們可能授權或收購的資產為股東創造回報。

Your next question...

你的下一個問題…

Let me just -- sorry. Just quickly, I don't think I addressed your nephrology question. We don't have as much active research in nephrology and bone at the moment and -- because we haven't seen internally opportunities to advance novel therapies there. We think the medicines we have are addressing the needs in the marketplace very effectively. But to the extent that there are things outside of Amgen that fit well with our 30 years of leadership, for example, nephrology or with our global leadership in bone, then we pay close attention to that as well.

讓我先——抱歉。簡單說一下，我好像還沒回答您關於腎臟病的問題。目前我們在腎臟病和骨科領域的研究並不多，因為我們內部還沒有看到推進這些領域新療法的機會。我們認為我們現有的藥物能夠非常有效地滿足市場需求。但是，如果安進以外的領域與我們30年來在腎臟病或骨科領域的領先地位相契合，我們也會密切關注。

Your next question is from Dane Leone with Raymond James.

您的下一個問題來自 Raymond James 的 Dane Leone。

And I'll add my congratulations to Arvind. Hope you have a fun birthday tonight after the call, so I'll keep it brief. My question is on Tarlatamab. Question for me here is what you guys think you need to see as you're planning for this Phase II study? Obviously, initial data seemed encouraging from the first 52 patients you had earlier this year. But where do you want to think about positioning this drug in the different lines of small cell lung cancer now? And what have you maybe seen as the dose escalation studies progressed since maybe we've seen the last data update that has you thinking about a pivotal study now?

我也要向Arvind表示祝賀。希望你今晚通話結束後能度過一個愉快的生日，所以我就長話短說。我的問題是關於Tarlatamab的。我想問的是，當你們計劃進行這項II期研究時，你們認為需要觀察哪些面向？顯然，今年早些時候你們招募的首批52名患者的初步數據看起來令人鼓舞。但是，現在你們打算如何定位這種藥物在小細胞肺癌的不同治療領域？自從我們看到上次的數據更新以來，隨著劑量遞增研究的進展，你們觀察到了哪些情況，以至於現在考慮進行一項關鍵性研究？

Yes. Thanks, Dane. I think to take the last part of your question first, what we've seen are ongoing response rate consistent with -- response rates consistent with the data that you saw from the later cohorts that we presented a month or 2 ago. And in addition, we've actually been impressed with duration of response. Most of these patients are third line plus, which, as you know, is a very aggressive disease in small cell lung cancer. And durable responses here are vanishingly rare. So that, I think, is, in addition, what really gives us encouragement here.

是的，謝謝，丹恩。我想先回答你問題的最後一部分，我們目前觀察到的持續緩解率與我們一兩個月前公佈的後期隊列數據一致。此外，緩解持續時間也給我們留下了深刻的印象。這些患者大多是第三線及以上治療，如你所知，小細胞肺癌是一種侵襲性很強的疾病。而持久緩解在這裡極為罕見。所以，我認為，這正是真正讓我們感到鼓舞的原因。

As we discuss potential registrational path with the FDA in the coming weeks, I think we'll focus on the patient population. But I think the initial foray is likely to be those later lines of therapy.

在接下來的幾周里，我們將與FDA討論潛在的註冊途徑，我認為我們將專注於患者群體。但我認為最初的嘗試很可能是針對後期治療方案。

We are moving forward in our development program now and are actively investigating earlier lines of therapy as well. That is clearly the end game that we're pointing for with Tarlatamab given the sort of activity that we're seeing in the clinic right now.

我們目前正在推動研發項目，並積極探索更早的治療方案。鑑於我們目前在臨床上觀察到的療效，這顯然是我們使用Tarlatamab的最終目標。

Your next question is from Michael Schmidt with Guggenheim.

你的下一個問題來自古根漢美術館的麥可·施密特。

I have one more on LUMAKRAS. And Arvind, congrats from me as well. So I guess should -- hypothetically, should the efficacy safety profile of the LUMAKRAS PD-1 inhibitor combinations turn out to be insufficient, which, I guess, could be possible, what are other likely avenues to possibly enable access to a broad first-line KRAS non-small cell lung cancer indication? Should we think about potential chemo combinations? Or are there others that are logical come to mind?

關於LUMAKRAS，我還有一個問題。 Arvind，也恭喜你。所以我想問的是－假設LUMAKRAS PD-1抑制劑聯合療法的療效和安全性不足（我想這並非不可能），還有哪些途徑可以使其適用於廣泛的KRAS突變非小細胞肺癌一線治療？我們是否應該考慮潛在的化療合併方案？或是有其他更合理的方案嗎？

Yes. Thanks, Michael. I think you're exactly right. It would be chemotherapy combinations, number one. And then going into biomarker selected populations, as we've discussed in terms of our planned upcoming first-line study, which we'll be launching shortly. And so should checkpoint inhibitor combinations not be feasible, I would expect that we would piece together other routes to first line to find patients who are most likely to benefit.

是的，謝謝你，麥可。我覺得你說得完全正確。首先是化療合併方案。然後，我們會根據生物標記篩選出特定族群，就像我們之前討論過的，我們即將啟動一項第一線治療研究。如果免疫檢查點抑制劑聯合方案不可行，我們預期會探索其他第一線治療途徑，以找到最有可能受益的患者。

Okay. Erica, as we're pushing up against the top of the hour, why don't we take our final 2 questions?

好的。艾麗卡，眼看快到整點了，我們不如來回答最後兩個問題吧？

Your next question is from Brian Skorney with Baird.

下一個問題來自 Baird 公司的 Brian Skorney。

Happy birthday, Arvind. Digging a little more on the disclosed notice of deficiency today. I think last year, you also received an RAR and modified RAR related to 2013 through 2015 and are also under investigation for 2016 through 2018 by the IRS. It just seems like there's all related to issues around profit allocation in Puerto Rico. So I was wondering if you could just kind of like walk through the next steps in terms of the tax court petition? Can the petition to be heard in the tax court fail? And if it does go to court and the decision goes against you, does that sort of establish precedence for the other years as well? And based on the IRS calculation methodology for 2010, for 2012, have you run that same calculation to establish what an upper bound of liability for 2013 through now would be?

生日快樂，Arvind。今天我進一步了解了你收到的欠稅通知。我想去年你也收到了一份關於2013年至2015年的稅務追繳通知（RAR）和一份修改後的稅務追繳通知（Modified RAR），而且國稅局（IRS）還在調查你2016年至2018年的稅務情況。看起來這一切都與波多黎各的利潤分配問題有關。所以我想請教一下，關於向稅務法庭提起訴訟的下一步是什麼？向稅務法庭提起訴訟有可能失敗嗎？如果訴訟真的開庭了，而你的判決對你不利，這是否會對其他年份的案件產生影響？另外，根據國稅局2010年和2012年的計算方法，你是否也計算過2013年至今的應繳稅款上限是多少？

Brian, thanks for the question. Look, we filed a petition with the U.S. tax court, in this case, could take several years to resolve. The IRS is also proposing significant adjustments to 2013 to '15 related to the similar issues, as you know. We disagree -- strongly disagree with the proposed adjustments. We're pursuing resolution with the IRS administrative appeals office on that. The IRS, as you noted, they're currently auditing years 2016 through '18. And so yes, we're sure they'll take the same position for the other periods under audit, and we believe that we have adequate reserves for that.

布萊恩，謝謝你的提問。是這樣的，我們已經向美國稅務法院提交了請願書，這個案子可能需要幾年時間才能解決。如你所知，國稅局也提議對2013年至2015年的相關問題進行重大調整。我們不同意——強烈反對這些調整提案。我們正在就此問題向國稅局行政上訴辦公室尋求解決方案。正如你所提到的，國稅局目前正在審計2016年至2018年。所以，是的，我們確信他們對其他正在審計的時期也會採取同樣的立場，而且我們相信我們有足夠的儲備金來應對這種情況。

Let's go to the final question.

我們來看最後一個問題。

Your final question is from Tim Anderson with Wolfe Research.

最後一個問題來自 Wolfe Research 的 Tim Anderson。

This is Andrew Galler, on for Tim. I just wanted to ask one question on teze. So given your partner, AstraZeneca, officially discontinued atopic dermatitis last week, can you just have any impact on your competitive positioning, especially in eosinophilic asthma compared to Dupi given the high coincidence of these atopic conditions?

我是 Andrew Galler，替 Tim 發言。我只想問一個關於 Teze 的問題。鑑於您的伴侶阿斯利康上周正式停止了異位性皮膚炎的治療，這會對您的競爭地位產生什麼影響嗎？尤其是在嗜酸性粒細胞性氣喘領域，考慮到這兩種特異性疾病的高度重疊性，與 Dupi 相比，Teze 的競爭地位會受到影響嗎？

Yes. I mean I think the short answer there is no, and we remain extremely bullish about tezepelumab given its activity across a range of patients with asthma regardless of eosinophil count. As we mentioned, we were granted priority review by the FDA, clearly an acknowledgement of the potential fit of this medicine with a large residual unmet medical need. So that doesn't really give us pause at all, Tim.

是的。我的意思是，簡而言之，答案是否定的。鑑於tezepelumab對各種嗜酸性粒細胞計數的氣喘患者均有效，我們仍然對其前景非常看好。正如我們之前提到的，FDA授予了我們優先審查資格，這顯然是對該藥物潛在契合巨大未滿足醫療需求的認可。所以，提姆，這根本沒讓我們有任何猶豫。

Okay, Erica. Well, let me just thank our callers for joining the call today. We're excited about the second half of the year. A lot going on here. And so we look forward to having the opportunity to gather with you in October and update you on the next quarter. Appreciate your interest in Amgen. Thank you.

好的，艾麗卡。首先，我要感謝各位今天參與電話會議。我們對下半年充滿期待，因為有很多事情正在發生。我們期待在十月有機會與大家再次相聚，並向大家報告下一季的最新情況。感謝您對安進的關注。謝謝。

Thanks, everybody.

謝謝大家。

And this concludes Amgen's Second Quarter 2021 Financial Results Conference Call. You may now disconnect.

安進公司2021財年第二季財務業績電話會議到此結束。您可以斷開連線了。