美國安進 (AMGN) 2020 Q4 法說會逐字稿

My name is Erica, and I will be your conference facilitator today for Amgen's Fourth Quarter 2020 Financial Results Conference Call. (Operator Instructions)

我是 Erica，今天我將擔任安進公司 2020 年第四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。

Okay. Thank you, Erica. Good afternoon, everybody. Welcome to our call to review our Q4 and full year financial results for 2020. I would say the strong execution despite the pandemic and pipeline advancement are 2 themes that were pervasive, so let's get after it. We'll stick to an efficient format of limited prepared comments, our 1 question rule, as Erica pointed out, and the overall duration of the call to 1 hour.

好的。謝謝Erica。大家下午好。歡迎參加我們2020年第四季及全年財務業績回顧電話會議。我想說，儘管面臨疫情挑戰，我們依然保持了強勁的執行力，而專案儲備也取得了進展，這兩點是本次會議的兩大亮點，那麼讓我們開始吧。我們將採用高效率的會議形式，包括有限的準備發言、Erica提到的「一問一答」規則，以及將會議總時長控制在1小時以內。

Slides have been posted. Just a quick reminder that we'll use non-GAAP financial measures in our presentation, and some of the statements will be forward-looking. Our SEC filings identify factors that could cause our actual results to differ materially.

幻燈片已上傳。再次提醒，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）的文件已列明可能導致實際結果與預期結果有重大差異的因素。

So with that, I would like to turn the call over to our Chairman and CEO, Bob Bradway. Bob?

那麼，接下來我想把電話交給我們的董事長兼執行長鮑伯‧布拉德韋。鮑伯？

Great. Thank you, Arvind, and thank all of you for joining our call. I'll start today by discussing Amgen's performance in 2020, and then provide some perspective on our priorities for 2021.

好的。謝謝Arvind，也謝謝各位參加我們的電話會議。今天我先會談談安進公司2020年的業績，然後再展望一下我們2021年的工作重點。

By any measure, 2020 was a very successful year for us. Despite the disruption of COVID-19, we delivered strong sales and earnings, driven by volume growth of 15% for our products. We advanced our innovative pipeline, most notably sotorasib and tezepelumab, both of which have received Breakthrough Therapy Designation from the FDA.

無論從哪個角度來看，2020年對我們來說都是非常成功的一年。儘管受到新冠疫情的影響，我們依然實現了強勁的銷售額和盈利，這主要得益於我們產品銷量增長了15%。我們推進了創新產品線的研發，其中最值得一提的是sotorasib和tezepelumab，這兩種藥物都已獲得FDA授予的突破性療法認定。

We successfully integrated Otezla, strengthening our decades-long leadership in inflammation with a $2 billion-plus product that we believe has runway for further global growth. We grew our sales outside the U.S. to more than $6 billion, delivering on long-term goals by expanding our presence in China and Japan with successful transactions in both markets. We did all this while staying focused on the health and safety of our 24,000 employees around the world. And to all of them, I want to say thank you for a job well done.

我們成功整合了Otezla，憑藉這款年銷售額超過20億美元的產品，鞏固了我們在發炎治療領域數十年的領先地位，我們相信該產品在全球範圍內仍有進一步增長的空間。我們在美國以外的銷售額成長至超過60億美元，透過在中國和日本成功完成交易，擴大了業務，實現了長期目標。在所有這些成就的同時，我們始終將全球24,000名員工的健康和安全放在首位。在此，我要對所有員工表示衷心的感謝，感謝你們的辛勤付出。

As we look to 2021, we're embracing 3 realities. First, COVID-19 is leading to some lasting changes in how we do business. For example, we expect to continue leveraging digital capabilities, call on customers and run clinical trials around the world with improved speed, efficiency, effectiveness.

展望2021年，我們正積極應對三大現實。首先，新冠疫情正在為我們的業務營運帶來一些持久性的變化。例如，我們預計將繼續利用數位化能力，以更快的速度、更高的效率和更有效的手段與客戶溝通，並在全球範圍內進行臨床試驗。

Second, we expect ongoing pressure on drug prices across the industry. We are fortunate to have products like Repatha, Prolia and Aimovig that meet the needs of millions of patients and can grow through increased penetration of the appropriate patient populations. Our industry-leading portfolio of biosimilars is also well positioned for the future.

其次，我們預期整個產業的藥品價格將持續承壓。幸運的是，我們擁有瑞百安（Repatha）、普羅利亞（Prolia）和艾莫維格（Aimovig）等產品，這些產品滿足了數百萬患者的需求，並且可以透過提高目標患者群體的市場滲透率來實現成長。我們在業界領先的生物相似藥產品組合也為未來發展做好了充分準備。

Third is capital continues to flow into our sector. We've entered a time of intense competition, where speed of execution is paramount. We've built a track record, featuring quality and speed. We've shown that with innovative first-in-class medicines like Repatha, the first approved PCSK9 inhibitor; and Aimovig, the first approved CGRP inhibitor. We showed it also with biosimilars like MVASI and KANJINTI, the first approved biosimilars to Avastin and Herceptin here in the U.S. And we're doing it right now with sotorasib, the first KRAS G12C inhibitor to be filed for approval just 28 months after we dosed our first patient. And we expect to do it again later in the year with tezepelumab as the first TSLP inhibitor.

第三，資本持續流入我們所在的產業。我們已進入競爭激烈的時代，執行速度至關重要。我們憑藉高品質和高效率的業績贏得了良好的口碑。我們透過創新首創藥物證明了這一點，例如首個核准的PCSK9抑制劑Repatha和首個核准的CGRP抑制劑Aimovig。我們也透過生物相似藥證明了這一點，例如MVASI和KANJINTI，它們分別是美國首批獲批的Avastin和Herceptin生物相似藥。目前，我們正在推進sotorasib的研發，這是首個KRAS G12C抑制劑，在首例患者用藥後僅28個月就提交了上市申請。我們預計今年晚些時候，tezepelumab將作為首個TSLP抑制劑再次取得突破。

We're excited about our pipeline and plan on increasing our R&D investment in 2021. Dave will speak in a moment about some of our promising mid-stage pipeline candidates. But since this is the time of year when I like to address our long-term investments, I want to focus for a moment on a couple of areas central to our early research strategy. These are areas where we are building differentiated capabilities.

我們對目前的研發管線充滿信心，並計畫在2021年加大研發投入。戴夫稍後會介紹一些我們前景看好的中期研發候選藥物。不過，由於每年這個時候我都會專注於我們的長期投資，所以我想先著重談談我們早期研發策略中的幾個核心領域。在這些領域，我們正在建立差異化的能力。

First, in human genetics, where we have industry leading capabilities, we are adding to our database approximately 1 million subjects from the U.S. and the U.K. for whom we will have extensive phenotypic and genotypic information. This will augment the data we already have on in excess of 1.5 million individuals.

首先，在人類遺傳學領域，我們擁有領先業界的能力，我們正在將來自美國和英國的約100萬名受試者的數據添加到我們的資料庫中，我們將擁有這些受試者的詳盡表型和基因型資訊。這將擴充我們已有的超過150萬人的數據。

In addition, we're pioneering the use of large-scale proteomics to measure the relative levels of some 5,000 different proteins in the blood. We're excited about the insights we're generating from this genomic proteomic work and expect to benefit in the selection of new drug targets and clinical trial design.

此外，我們正在率先利用大規模蛋白質體學技術來測量血液中約5000種不同蛋白質的相對水平。我們對這項基因組蛋白質體學研究獲得的見解感到興奮，並期望從中受益，從而有助於新藥標靶的選擇和臨床試驗的設計。

There's growing interest in our industry in the area of targeted protein degradation, we believe the opportunity is broader than that, and our efforts are not just limited to degrading proteins. We're looking at degrading other biologic molecules as well. We're designing molecules to have multi-specific activity through a principle we call induced proximity. The idea is to use this platform to dramatically expand the universe of druggable targets. It's still early days in the field, but I wanted to flag it as an area where we want to emerge through time as an industry leader.

我們產業對標靶蛋白降解領域的興趣日益濃厚，但我們認為其發展前景遠不止於此，我們的研究並非僅限於降解蛋白質。我們還在探索降解其他生物分子。我們正在設計具有多重特異性活性的分子，其原理被稱為「誘導鄰近效應」。我們的目標是利用此平台大幅拓展可成藥標靶的範圍。雖然該領域尚處於起步階段，但我希望強調，我們希望未來能成為該領域的產業領導者。

All of our work is taking place at a time when more is expected of companies than ever before. Amgen is advancing an ambitious ESG agenda that includes providing medicines at no cost to low-income patients and funding world-class STEM education programs. With respect to the environment, we're committed to achieving carbon neutrality by 2027, along with a 40% reduction in water use and a 75% reduction in waste.

我們所有工作的發展都處於一個企業面臨前所未有的更高期望的時代。安進正在推動一項雄心勃勃的ESG（環境、社會和治理）議程，其中包括為低收入患者免費提供藥品，以及資助世界一流的STEM（科學、技術、工程和數學）教育計畫。在環境方面，我們致力於在2027年實現碳中和，同時將用水量減少40%，廢棄物量減少75%。

In summary, our success in 2020 gives me great confidence in our ability to deliver in 2021 and beyond. The world needs more innovation, not less, and we've proven ourselves ready, willing and able to provide it.

總而言之，我們在2020年的成功讓我對我們2021年及以後的發展能力充滿信心。世界需要更多創新，而不是更少，而我們已經證明，我們隨時準備好、願意並且能夠提供創新。

I look forward to your questions a little later on in the call. Right now, let me turn over to Dave Reese, our Head of R&D.

我期待稍後回答各位的問題。現在，我把麥克風交給我們的研發主管戴夫‧里斯。

Thanks, Bob, and good afternoon, everyone. I'll begin today with sotorasib, our first-in-class KRAS G12C inhibitor. To date, more than 700 patients have been treated across 5 continents, and we are accelerating this groundbreaking program into new indications and earlier lines of therapy. A few days ago, we presented the first pivotal data for a KRAS G12C inhibitor at the World Conference on Lung Cancer, where we reported on 126 patients with second-line plus non-small cell lung cancer.

謝謝鮑勃，大家下午好。今天我首先要介紹的是索托拉西布（sotorasib），這是我們首創的KRAS G12C抑制劑。迄今為止，已有來自五大洲的700多名患者接受了該藥物治療，我們正在加速推進這項突破性項目，將其應用於新的適應症和更早的治療方案。幾天前，我們在世界肺癌大會上發表了首個KRAS G12C抑制劑的關鍵性數據，報告了126例二線及以上非小細胞肺癌患者的治療結果。

Sotorasib drove rapid, deep and durable responses across a broad range of mutational profiles and subgroups with poor prognoses. And a centrally adjudicated intent-to-treat analysis, the objective response rate was 37%, including 3 complete remissions, progression-free survival was 6.8 months and duration of response was 10 months. Importantly, sotorasib demonstrated a very tolerable and differentiated clinical profile. And based on these data, we completed regulatory submissions in the United States and EU in December.

索托拉西佈在多種突變譜和預後不良的亞群中均能誘導快速、深度且持久的緩解。經中心裁定的意向性治療分析顯示，客觀緩解率為37%，其中包括3例完全緩解，無惡化存活期為6.8個月，緩解持續時間為10個月。重要的是，索托拉西布展現出良好的耐受性和差異化的臨床特徵。基於這些數據，我們已在12月完成了在美國和歐盟的監管申報。

More recently, we submitted files in Canada, the U.K., Brazil and Australia with additional global submissions anticipated in the coming weeks and months and launch preparations are well advanced. The Phase III non-small cell lung cancer monotherapy study versus docetaxel continues to advance nicely, as do our 10 combination cohorts and Phase II colorectal study, with data expected from these latter 2 beginning in the first half of this year.

最近，我們已向加拿大、英國、巴西和澳洲提交了申請文件，預計未來幾週和幾個月內也將提交更多全球申請，上市準備工作進展順利。針對非小細胞肺癌的單藥治療III期研究（與多西他賽對比）進展良好，我們的10個聯合用藥隊列研究和II期結直腸癌研究也進展順利，預計後兩項研究的數據將於今年上半年公佈。

We will initiate a Phase II study in first line non-small cell lung cancer in the second quarter, where we will investigate sotorasib monotherapy in patients most likely to benefit based on tumor profiling. For example, those tumors harboring STK11 mutations.

我們將於第二季啟動一項針對第一線非小細胞肺癌患者的II期臨床研究，該研究將基於腫瘤特徵分析，探討索托拉西佈單藥治療最有可能獲益的患者（例如攜帶STK11突變的腫瘤患者）的療效。

Finally, we recently cleared the safety hurdle at the full sotorasib dose in our MEK inhibitor combination study and have completed enrollment in an expansion cohort.

最後，我們最近在 MEK 抑制劑聯合研究中，以全劑量 sotorasib 克服了安全性障礙，並完成了擴展隊列的招募。

In inflammation, along with our partner, AstraZeneca, we look forward to presenting the results from the Phase III NAVIGATOR study at the American Academy of Allergy Asthma and Immunology Virtual Annual Meeting, also known as AAAAI, at the end of February. You may have seen the abstract posting yesterday, which results from the primary and key secondary end points data that, in our view, provide a compelling rationale for the potential utility of tezepelumab in a broad population of patients with severe uncontrolled asthma, including those with low eosinophil counts or we have Breakthrough Therapy Designation in the United States. We are working closely with AstraZeneca on our U.S. and EU filing packages, which we expect to submit in the first half.

在發炎領域，我們與合作夥伴阿斯利康期待在2月底舉行的美國過敏、氣喘和免疫學會虛擬年會（AAAAI）上公佈III期NAVIGATOR研究的結果。您可能已經看到了昨天發布的摘要，該摘要基於主要終點和關鍵次要終點數據，我們認為這些數據為tezepelumab在包括嗜酸性粒細胞計數低的患者在內的廣泛重度未控制哮喘患者群體中的潛在療效提供了令人信服的理論依據。此外，我們已獲得美國突破性療法認定。我們正與阿斯特捷利康緊密合作，準備美國和歐盟的申報文件，預計上半年提交。

Turning to our BiTE platform. We are particularly excited about the rapid progress we are making with 2 solid tumor programs, AMG 160, targeting prostate-specific membrane antigen, or PSMA, for castrate-resistant prostate cancer; and AMG 757, targeting DLL3 for small cell lung cancer. AMG 160 is currently in dose expansion, and we expect to advance AMG 757 into dose expansion in the coming months. We are quite pleased with the clinical profiles we are seeing with both of these molecules.

接下來談談我們的BiTE平台。我們尤其欣喜地看到兩項實體瘤計畫的快速進展：AMG 160靶向前列腺特異性膜抗原（PSMA），用於治療去勢抵抗性前列腺癌；AMG 757靶向DLL3，用於治療小細胞肺癌。 AMG 160目前正在進行劑量擴展試驗，我們預計AMG 757也將在未來幾個月內進入劑量擴展階段。我們對這兩種分子的臨床療效都非常滿意。

And as you will see in our press release, we also continue to actively prioritize our oncology portfolio. In migraine, Aimovig continues to demonstrate important benefits for patients as our colleagues at Novartis announced positive Phase IV results showing superior efficacy and safety of Aimovig over topiramate in the migraine prevention setting. Finally, our biosimilars portfolio continues to advance, and we have completed enrollment in our Phase III study of ABP 959, our biosimilar Soliris.

正如您將在我們的新聞稿中看到的那樣，我們也將繼續積極優先發展腫瘤產品組合。在偏頭痛領域，Aimovig 持續展現出對患者的重要益處，我們的諾華同事宣布了積極的 IV 期臨床試驗結果，表明 Aimovig 在偏頭痛預防方面優於托吡酯，且療效和安全性更佳。最後，我們的生物相似藥產品組合也在不斷推進，我們已完成生物相似藥 Soliris（ABP 959）的 III 期臨床試驗的患者招募。

In closing, I'd like to thank our staff for their ongoing efforts to deliver our portfolio for patients. Murdo?

最後，我要感謝我們的員工為患者提供產品組合所付出的持續努力。默多？

Thanks, Dave. 2020 product sales grew 9% year-over-year, driven by 15% volume growth, with roughly equal growth rates in the U.S. and internationally.

謝謝戴夫。 2020年產品銷售額年增9%，主要得益於銷售成長15%，美國和國際市場的成長率大致相同。

Starting with our innovative portfolio, Prolia grew year-over-year despite significant impacts from the pandemic. And EVENITY sales increased 85% year-over-year, driven by strong volume growth. Repatha is now annualizing at over $1 billion in revenues with 67% year-over-year volume growth.

憑藉我們創新的產品組合，Prolia儘管受到疫情的嚴重影響，仍實現了同比增長。 EVENITY的銷售額年增85%，主要得益於強勁的銷售成長。 Repatha的年化收入已超過10億美元，銷量較去年同期成長67%。

In the first full year since acquisition, we've seamlessly integrated Otezla growing total prescriptions by 13% year-over-year. And finally, our biosimilars portfolio totaled $1.7 billion in sales.

收購後的第一個完整年度，我們順利整合了 Otezla，處方總量年增 13%。最後，我們的生物相似藥產品組合總銷售額達到 17 億美元。

Moving to fourth quarter performance. Product sales grew 8% year-over-year, driven by 13% volume growth. In our bone franchise, we remain focused on ensuring patient continuity. By year-end, osteoporosis diagnoses reached approximately 80% of pre-COVID levels, leading to a positive trend in new patient starts entering 2021.

接下來是第四季業績。產品銷售額較去年成長8%，主要得益於銷售成長13%。在骨科領域，我們始終致力於確保患者治療的連續性。到年底，骨質疏鬆症的診斷數量已恢復到新冠疫情前水準的約80%，這預示著2021年新患者數量將呈現正面成長趨勢。

In Q4, Prolia's repeat patient numbers were lower than historical trends as a result of the echo effect of COVID disruption in Q2. EVENITY sales grew quarter-over-quarter. We believe EVENITY's unique bone building profile will continue to drive growth in our franchise as physicians appreciate its benefit-risk profile for treating their high-risk post fracture patients.

第四季度，受第二季度新冠疫情衝擊的持續影響，Prolia的複診患者數量低於歷史平均。 EVENITY的銷售額較上季成長。我們相信，EVENITY獨特的骨骼重建特性將繼續推動我們產品線的成長，因為醫生們會認可其在治療高風險骨折後患者方面的獲益風險比。

In cardiovascular, Repatha remains the global PCSK9 leader. Net sales in Q4 were $253 million, driven by sequential volume growth and stable U.S. net price. As we enter 2021, we expect continued momentum for this brand globally, driven by growth from international markets, improved U.S. PBM formulary position and relatively stable net price in the U.S.

在心血管領域，瑞百安（Repatha）依然是全球PCSK9抑制劑的領導者。第四季淨銷售額達2.53億美元，主要得益於銷售季成長和美國市場淨價的穩定。展望2021年，我們預期品牌在全球範圍內將繼續保持成長勢頭，這主要得益於國際市場的成長、美國藥品福利管理機構（PBM）處方集地位的提升以及美國市場相對穩定的淨價。

Moving on to Aimovig, which is the market leader in the highly competitive CGRP class, volumes grew 21% year-over-year in the fourth quarter, but remained flat quarter-over-quarter as the pandemic negatively impacted new patient starts.

接下來是 Aimovig，它是競爭激烈的 CGRP 類別中的市場領導者。第四季銷量年增 21%，但由於疫情對新患者開藥產生了負面影響，因此環比銷量保持穩定。

Next to Parsabiv. Q4 sales declined 8% quarter-over-quarter in the U.S. as some customers decreased utilization, while others built inventory in advance of the January reimbursement change. With Parsabivs inclusion in the end-stage renal disease bundle, we expect sales to decline by approximately 40% to 50% in 2021 as U.S. dialysis centers update their treatment protocols to accommodate generic forms of cinacalcet.

僅次於Parsabiv。由於部分客戶減少了用藥量，而另一些客戶則在1月報銷政策調整前囤積了庫存，導致Parsabiv在美國的第四季度銷售額環比下降了8%。隨著Parsabiv被納入末期腎病治療方案，我們預計2021年其銷售額將下降約40%至50%，因為美國透析中心需要更新治療方案以適應西那卡塞的仿製藥。

We also expect sales in Q1 to be the lowest of the year as customers deplete $40 million of inventory build in the second half of 2020. For patients on hemodialysis, Parsabiv is the only IV-administered calcimimetic that lowers and maintains key secondary hyperparathyroidism lab values. Also, Parsabiv offers providers control over calcimimetic delivery and the opportunity to reduce patient pill burden.

我們預計第一季的銷售額將是全年最低的，因為客戶將在2020年下半年消耗掉價值4,000萬美元的庫存。對於接受血液透析的患者，Parsabiv是唯一能夠降低並維持關鍵繼發性副甲狀腺功能亢進實驗室指標的靜脈注射類鈣劑。此外，Parsabiv也使醫護人員能夠更好地控制類鈣劑的給藥，並有助於減輕患者的服藥負擔。

Transitioning to our inflammation portfolio, Otezla sales were $617 million in Q4, driven by a 13% year-over-year increase in total U.S. prescriptions. We see attractive future growth opportunities through global launches, and our planned submission for the mild to moderate psoriasis indication in the U.S. in the coming weeks.

轉向我們的發炎產品組合，Otezla第四季銷售額達6.17億美元，主要得益於美國處方總量年增13%。我們看到了透過全球上市以及計劃在未來幾週內向美國提交治療輕度至中度銀屑病適應症的上市申請，未來成長前景廣闊。

With Enbrel, fourth quarter sales declined 5% year-over-year. Volumes declined from gradual share loss, coupled with slower growth in the rheumatology segment, which we attribute in part to the pandemic.

恩利（Enbrel）第四季銷售額較去年同期下降5%。銷售下降的原因是市佔率逐漸流失，以及風濕病領域成長放緩，我們認為這部分是由於疫情的影響。

For 2020, net price declined in the low single digits, and we expect volume and net price trends to persist in 2021. Enbrel has an established record of safety and efficacy, and we will continue to invest in innovative solutions to enhance the patient experience.

2020年，淨價下降幅度為個位數，我們預期2021年銷售量和淨價趨勢將持續。恩利（Enbrel）具有良好的安全性和有效性記錄，我們將繼續投資於創新解決方案，以改善患者體驗。

Switching to biosimilars. Q4 sales were $541 million, driven by volume growth which was partially offset by declines in net selling price. We are leading in biosimilar share in Europe for AMGEVITA and in the U.S. for MVASI and KANJINTI, with a respective 48% and 41% average share in Q4.

轉向生物類似藥。第四季銷售額為5.41億美元，主要得益於銷售成長，但部分被淨售價下降所抵銷。我們在歐洲的生物相似藥市場佔有率中處於領先地位，AMGEVITA位居榜首；在美國，MVASI和KANJINTI也處於領先地位，第四季平均市佔率分別為48%和41%。

We recently launched our fifth biosimilar, RIABNI, a biosimilar to Rituxan. For 2021, we expect biosimilar volume growth to be partially offset by a decline in net selling prices due to increased competition.

我們近期推出了第五款生物相似藥RIABNI，它是利妥昔單抗（Rituxan）的生物相似藥。我們預計，2021年生物相似藥銷售成長將因競爭加劇導致的淨售價下降而部分抵銷。

In oncology, Neulasta Onpro remains the preferred long-acting G-CSF with 54% share of volume in the quarter. Onpro continues to demonstrate the value of innovation allowing patients to receive their G-CSF treatment without having to return to their doctor's office or other site of care for administration.

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，本季市佔率高達 54%。 Onpro 持續展現創新價值，讓患者無需返回診所或其他醫療機構即可接受 G-CSF 治療。

Overall, Neulasta sales decreased 19% year-over-year, driven by declines in volume and net selling price. And the most recent published average selling price for Neulasta in the U.S. declined 28% year-over-year. Going forward, we expect the price and volume trends to persist as biosimilar competition increases.

整體而言，受銷量和淨售價雙雙下滑的影響，Neulasta的銷售額年減了19%。而Neulasta在美國最新公佈的平均售價較去年同期下降了28%。展望未來，隨著生物相似藥競爭的加劇，我們預期價格和銷售下滑的趨勢將持續下去。

Looking ahead, we're excited about new opportunities across our business. Internationally, we recently received national reimbursement drug listing for Prolia, which will accelerate growth in China. In Japan, we're preparing for the launch of Aimovig, and we're planning for the launch of our biosimilar brands across multiple markets in 2021.

展望未來，我們對公司各業務領域的新機會感到振奮。在國際市場，我們近期獲得了Prolia在中國的國家健保報銷資格，這將加速公司在中國的成長。在日本，我們正積極籌備Aimovig的上市，並計劃於2021年在多個市場推出我們的生物相似藥品牌。

Finally, our team is ready to launch sotorasib upon approval, and we're excited to establish it as a foundational therapy for patients with advanced lung cancer. And we're also preparing for the launch of tezepelumab with our partner, AstraZeneca, and are enthusiastic about the prospect of having a therapy that can help treat the 2.5 million people in the world living with severe uncontrolled asthma. Overall, I'm pleased with our Q4 and full year performance and look forward to Amgen serving more patients in 2021.

最後，我們的團隊已做好準備，一旦sotorasib獲得批准即可上市，我們非常高興能將其確立為晚期肺癌患者的基礎療法。同時，我們也與合作夥伴阿斯特捷利康共同籌備tezepelumab的上市，並對這款有望幫助全球250萬重度未控制氣喘患者的療法充滿期待。總而言之，我對我們第四季度和全年的業績感到滿意，並期待安進在2021年為更多患者提供服務。

And I'll turn it over to Peter.

然後我把它交給彼得。

Thank you, Murdo. Good afternoon, and good evening, everyone. We are pleased with our strong execution and performance in the fourth quarter and for the full year 2020. In Q4, we delivered 7% revenue and 5% non-GAAP EPS year-over-year growth. For the full year, we delivered 9% revenue and 12% non-GAAP EPS year-over-year growth.

謝謝，默多。大家下午好，晚上好。我們對第四季和2020年全年的強勁業績感到非常滿意。第四季度，我們的營收年增7%，非GAAP每股盈餘較去年同期成長5%。全年來看，我們的營收年增9%，非GAAP每股盈餘較去年同期成長12%。

As Murdo mentioned, both Q4 and the full year benefited from volume-driven sales growth of 13% and 15%, respectively. Non-GAAP operating expenses increased 9% year-over-year in the fourth quarter as spend accelerated to advance our innovative pipeline, drive volume growth for much of our portfolio around the globe and prepare for future launches, particularly for sotorasib and tezepelumab.

正如默多所提到的，第四季和全年均受益於銷售成長，分別成長了13%和15%。第四季度非GAAP營運費用年增9%，主要原因是為推進創新產品線、推動全球大部分產品組合的銷售成長以及為未來的產品上市做準備（特別是sotorasib和tezepelumab），公司加大了支出力度。

Operating expense grew 7% for the full year, including a full year of Otezla-related activities and expenses. Free cash flow for the fourth quarter and the full year was $2.0 billion and $9.9 billion, respectively.

全年營運支出成長7%，其中包括與Otezla相關的全年活動和支出。第四季和全年自由現金流分別為20億美元和99億美元。

Now turning to the outlook for business for 2021 on Page 37. We look forward to investing in innovation in 2021 and in launching new products. We will also continue to execute on our volume-driven growth strategy. Due to COVID, we also anticipate some uncertainty and quarter-to-quarter variability in revenue and earnings throughout 2021, with potential recovery later in the year, contingent upon the speed and effectiveness of global vaccination.

現在請翻到第37頁，展望2021年的業務發展。我們期待在2021年加大創新投入，並推出新產品。同時，我們將繼續執行以銷售為導向的成長策略。受新冠疫情影響，我們預計2021年全年營收和獲利將存在一定的不確定性，並出現季度間波動。隨著全球疫苗接種速度和效果的提升，我們預計今年稍後可能會出現復甦。

Our 2021 revenue guidance is $25.8 billion to $26.6 billion, and our non-GAAP earnings per share guidance is $16 to $17 per share. GAAP earnings per share guidance is $12.12 per share to $13.17 per share.

我們預計2021年營收為258億美元至266億美元，非GAAP每股收益預計為16美元至17美元，GAAP每股收益預計為12.12美元至13.17美元。

Now let me mention several key assumptions embedded in our guidance. First, our revenue range reflects volume growth from Prolia, Otezla, Repatha, EVENITY, Aimovig and our biosimilars portfolio and importantly, our innovative oncology portfolio.

現在我想提及我們績效指引中蘊含的幾個關鍵假設。首先，我們的營收預期反映了Prolia、Otezla、Repatha、EVENITY、Aimovig以及我們的生物相似藥產品組合的銷售成長，尤其重要的是，也反映了我們創新腫瘤產品組合的銷售成長。

At the same time, we expect continued competition against our filgrastim and ESA franchises as well as accelerating erosion in U.S. Parsabiv sales, as Murdo highlighted. We experienced a 6% decline in net selling prices globally in 2020.

同時，正如默多所強調的，我們預期非格司亭和促紅血球生成素類藥物（ESA）產品線將持續面臨競爭，美國帕沙比夫的銷售額也將加速下滑。 2020年，我們全球淨售價下降了6%。

For 2021, we again expect mid-single-digit price declines. A couple of points to recall when considering Q1 of 2021. Historically, the first quarter represents the lowest product sales quarter of the year, with planned changes, insurance reverifications and higher co-pay expenses as U.S. patients work through deductibles, especially for products, including Enbrel, Otezla and Aimovig.

我們預計2021年價格將再次出現中等個位數的下降。在考慮2021年第一季時，有幾點需要注意。從歷史數據來看，第一季通常是全年產品銷售額最低的季度，因為計劃變更、保險重新核實以及美國患者自付額增加等因素都會影響銷售額，尤其是對於恩利（Enbrel）、奧特茲拉（Otezla）和艾莫維（Aimovig）等產品而言。

Additionally, I want to remind everyone that in Q1 2020, Enbrel benefited from approximately $115million (corrected by company after the call) of favorable changes to estimated sales deductions, and the entire portfolio saw roughly $100 million in inventory bill due to COVID.

此外，我想提醒大家，在 2020 年第一季度，Enbrel 受益於約 1.15 億美元的銷售扣除額估計值的有利變化（公司在電話會議後進行了更正），並且由於 COVID 疫情，整個產品組合的庫存支出約為 1 億美元。

So as a proportion of our full year sales, we expect Q1 2021 to be a slightly lower percentage than the 24% it was in Q1 2020. We expect other revenue to be in the range of approximately $1.4 billion to $1.5 billion for the full year 2021. This includes revenues from COVID-19 antibody manufacturing and profit share agreement with Lilly, under which we expect to begin shipping in the second quarter.

因此，我們預計2021年第一季將佔全年銷售額的比例將略低於2020年第一季的24%。我們預計2021年全年其他收入約為14億至15億美元。這包括新冠病毒抗體生產收入以及與禮來公司達成的利潤分成協議收入，根據該協議，我們預計將於第二季度開始出貨。

We expect 2021 total non-GAAP operating expenses to grow at a rate similar to the 7% 2020 non-GAAP operating expense growth. As we continue to invest in innovation, launches of new products and digitization efforts. We have created an industry-leading cost structure, and expect an operating margin of roughly 50% in 2021.

我們預計2021年非GAAP營運費用總額的成長率將與2020年7%的成長率相近。隨著我們持續投資於創新、新產品發布和數位轉型，我們已打造出業界領先的成本結構，並預計2021年營業利潤率約為50%。

Cost of sales as a percent of product sales will increase to a range of 16% to 17% due to an evolving product mix, and higher royalties and profit share payments. Additionally, cost of sales will increase in connection with our manufacturing agreement with Lilly. As I mentioned previously, the revenues and profit share will be included in other revenue.

由於產品組合的變化以及更高的特許權使用費和利潤分成，銷售成本佔產品銷售額的比例將上升至 16% 至 17%。此外，由於我們與禮來公司的生產協議，銷售成本也會增加。正如我之前提到的，收入和利潤分成將計入其他收入。

Research and development expenses will increase as our pipeline advances with year-over-year increases in early and late-stage investments. And SG&A will decline primarily due to changes in our commercial model including an increased focus on digital efforts.

隨著我們專案管線的推進，研發費用將會增加，早期和後期投資也將逐年成長。而銷售、管理及行政費用（SG&A）將下降，主要原因是我們的商業模式發生了變化，包括更加重視數位轉型。

Now let me take a moment to explain an update we are making to our non-GAAP policy. Effective January 2021, our non-GAAP results will no longer include fair value adjustments to equity investments. These adjustments to equity investments have historically been recorded in other income and expenses and we're positive in our 2020 non-GAAP results. This change will not apply to our strategic investment in BeiGene, which is included in our non-GAAP results and is accounted for under the equity method of accounting. The press release contains the pro forma 2020 results by quarter under our updated policy.

現在，請容許我花一點時間解釋一下我們對非GAAP財務報表政策的更新。自2021年1月起，我們的非GAAP財務報表將不再包含權益投資的公允價值調整。以往，這些權益投資的調整計入其他收入和支出，而我們在2020年的非GAAP財務報表中確認了這些調整為正值。這項變更不適用於我們對百濟神州的策略投資，該投資已計入我們的非GAAP財務報表，並採用權益法進行會計處理。新聞稿中包含了根據我們更新後的政策編製的2020年各季度備考財務報表。

We will also now use updated adjusted 2020 amounts that conform to this policy for comparison purposes going forward. Under our updated non-GAAP policy that I just explained, here is our guidance for other income and expense.

為了方便比較，我們將使用符合此政策的更新調整後的2020年數據。根據我剛才解釋的更新後的非GAAP政策，以下是我們對其他收入和支出的指引。

We anticipate non-GAAP other income and expense in the range of $1.3 billion to $1.5 billion of expense. This 2021 guidance reflects incorporation of 4 quarters of BeiGene's results versus 3 quarters in 2020, which are recorded on a 1 quarter lag. Recall that we only use the limited publicly available consensus estimates for BeiGene in connection with our guidance, and thus may experience additional variability depending on BeiGene's actual results. Our basis in BeiGene as of December 31, 2020, was approximately $2.9 billion, and this long-term investment is valued at approximately $6 billion today based upon the current U.S. market price.

我們預計非GAAP其他收入和支出將在13億美元至15億美元之間。 2021年的業績指引納入了百濟神州四個季度的業績數據，而2020年僅納入了三個季度的業績數據（由於存在一個季度的滯後），因此2021年的業績指引僅包含三個季度的業績數據。需要注意的是，我們在製定業績指引時僅使用了有限的公開市場共識預期，因此實際業績可能會有所波動。截至2020年12月31日，我們持有的百濟神州股份成本約為29​​億美元，根據目前的美國市場價格計算，這項長期投資的價值約為60億美元。

Our non-GAAP tax rate guidance is 13% to 14%. And we expect capital expenditures of approximately $900 million this year, including investments in additional manufacturing and other capacity to support our volume-driven growth strategy as well as an environmental sustainability initiatives that will enable our global operations to achieve carbon neutrality by 2027 and also in our digitization efforts to continue to scale up and integrate data and analytics in everything we do at Amgen.

我們非GAAP稅率預期為13%至14%。我們預計今年的資本支出約為9億美元，其中包括對額外生產和其他產能的投資，以支持我們以銷售為導向的成長策略，以及環境永續發展舉措，這將使我們的全球營運在2027年實現碳中和，同時也將用於我們的數位化工作，以繼續擴大規模並將數據和分析整合到安進的所有業務中。

And finally, our capital allocation hierarchy remains unchanged. After both internal and external innovation and then investing in our capital expenditures, we remain committed to returning capital to shareholders in the form of growing dividends, including the 10% increase in the first quarter of 2021 to $1.76 per share. We anticipate opportunistic share repurchases in the range of $3 billion to $4 billion, subject to our Board's authorization.

最後，我們的資本配置層級保持不變。在進行內部和外部創新以及資本支出之後，我們仍致力於以不斷增長的股息形式向股東返還資本，包括2021年第一季股息增長10%至每股1.76美元。我們預計將進行30億至40億美元的擇機股票回購，但需獲得董事會的批准。

So in summary, we deliver for patients, every patient every time. And for our investors in a challenging year that included the greatest public health crisis in 100 years, and the greatest economic disruption since the great depression. And we are confident in the outlook for Amgen's success in 2021 and beyond.

總而言之，我們始終致力於為每位患者提供優質服務。在充滿挑戰的一年裡，我們不僅為投資者帶來了回報，還應對了百年來最嚴重的公共衛生危機和自大蕭條以來最嚴重的經濟動盪。我們對安進在2021年及以後的成功前景充滿信心。

This concludes the financial update. I will now turn the call back over to Bob.

財務更新到此結束。現在我將把電話轉回給鮑伯。

Okay. Thank you, Peter. And Erica, let me invite you to remind our callers of our process for Q&A, and let's begin the question session.

好的。謝謝你，彼得。艾麗卡，請你提醒來電聽眾我們的問答環節流程，現在我們開始問答環節。

(Operator Instructions) Your first question in queue is from Alethia Young with Cantor Fitzgerald.

（操作員說明）您的第一個問題來自 Cantor Fitzgerald 的 Alethia Young。

Congrats on always a solid guide and great quarter. I just wanted maybe if you guys could talk a little bit about, obviously, the KRAS program and the combinations and maybe perhaps kind of -- I know they're probably early Phase I studies, but what you're kind of looking to glean from some of these different combinations? I know you get asked a lot about this, but just kind of as we're getting closer and closer, like how you think about unpacking that with different indications?

恭喜你們一直以來提供如此可靠的指導，本季也表現出色。我想請你們談談KRAS計畫以及相關的聯合療法，我知道它們可能還處於早期I期研究階段，但你們希望從這些不同的聯合療法中獲得什麼資訊呢？我知道你們常被問到這個問題，但隨著研究的推進，你們會如何看待這些療法在不同適應症的應用呢？

Alethia, thanks for the question. Yes, we do get this one quite a bit about the combinations. What I will say is there's no generic answer here. The -- it's going to depend on line of therapy and indication, non-small cell lung cancer, of course, colorectal cancer and then some of the other indications beyond that.

Alethia，謝謝你的提問。是的，我們常被問到關於合併用藥的問題。我想說的是，這個問題沒有統一的答案。這取決於治療方案和適應症，例如非小細胞肺癌、大腸癌，以及其他一些適應症。

Typically, you're looking for a 15%, 20%, 30% increment on any given end point beyond standard of care, but also looking at the totality of the data. I think in many of these settings, in particular, progression-free survival and ultimately, overall survival. So given the safety profile we've demonstrated to date, those are the sort of efficacy metrics that we'll probably take a look at.

通常情況下，我們會尋找在標準治療基礎上，任何特定終點指標提高 15%、20% 或 30% 的效果，但同時也要考慮所有數據。我認為在很多情況下，尤其是無惡化存活期和最終的總存活期，都非常重要。鑑於我們迄今為止所展現的安全性，這些可能是我們會重點關注的療效指標。

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。

I bet you're going to get a lot of combo KRAS questions, so I'm just going to ask as well. The MEK expansion cohort, David, I thought it's really exciting that you've actually completed enrollment. And I know, I guess, that was mentioned at the conference as well, that could be potentially pivotal. Can you talk about whether you would actually be able to announce data on that at some point this year? It's pivotal. Do you want the whole thing to be done before you report out on it? Could you have piecemeal data? And then maybe make a comment on the SHIP2 combo as well?

我猜你一定會收到很多關於KRAS組合的問題，所以我也想問一下。 David，關於MEK擴展隊列，我覺得你們已經完成招募真是太棒了。我知道，會議上也提到了這一點，這可能至關重要。可以談談今年某個時候是否能夠公佈相關數據嗎？這確實很關鍵。你們是希望所有數據都收集完畢後再發布報告嗎？還是可以分階段發布？之後，你們能不能也談談SHIP2組合隊列的狀況？

Yes. Thanks, Mike. Yes. No, we are very pleased with rapidity of enrollment in the MEK safety cohort. As we noted, we've moved beyond that to the expansion cohort. It's quite possible we'll have data from that over the course of this year. It will depend on just as the data come in and as we see those results.

是的，謝謝，麥克。是的，我們對MEK安全性隊列的快速入組非常滿意。正如我們之前提到的，我們已經進入了擴展隊列。我們很有可能在今年內獲得該隊列的數據。這取決於數據何時收集以及我們何時看到結果。

And again, it's too early to speculate on whether this could be pivotal or not. As I've mentioned, the master protocol from which these data are derived is essentially designed so that any given arm can be blown up into a pretty rigorous Phase II trial. And depending on indication and line of therapy, of course, we would make any sort of decisions regarding regulatory intent in that context.

再次強調，現在推測這是否具有關鍵意義還為時過早。正如我之前提到的，這些數據所依據的主方案的設計初衷是允許將任何一個試驗組擴展為相當嚴格的II期臨床試驗。當然，我們會根據適應症和治療方案，在相應的背景下做出任何有關監管意圖的決定。

So more to come as those data unfold, but we're quite happy with what we're seeing in terms of enrollment.

隨著數據的逐步公佈，我們還會發布更多信息，但我們對目前的招生情況相當滿意。

And SHIP2?

SHIP2 呢？

On SHIP2, it's moving along. I think biologically, that is a very interesting combination. And again, potentially more to come over the course of the year on that combination as well.

SHIP2專案進展順利。我認為從生物學角度來看，這是一個非常有趣的組合。而且，今年晚些時候，這個組合可能會有更多成果。

Your next question is from Terence Flynn with Goldman Sachs.

下一個問題來自高盛的 Terence Flynn。

Maybe just a 2-part from me. Maybe for Peter. I was just wondering as you look out the sustainability of that 50% operating margin, how you think about some of the puts and takes? And then any visibility into your biosimilar franchise, the margins there? I know that's a question we get frequently.

或許我只需要寫兩個部分。也許可以寫給彼得。我只是想知道，在考慮50%營業利潤率的可持續性時，您是如何看待一些利弊權衡的？另外，您對生物相似藥業務的利潤率有什麼了解嗎？我知道我們經常被問到這個問題。

And then, again, a higher level, and maybe for Bob, you mentioned protein degradation is an interesting platform on the forward that you guys are spending a lot of time building out. Do you expect to do that all internally? Or is that an area where you could also look externally for opportunities?

然後，再從更高的層面來說，也許對鮑勃來說，你提到蛋白質降解是一個很有趣的前鋒平台，你們正在投入大量時間來建造它。你們打算完全依靠內部力量完成這項工作嗎？還是說你們也會在這個領域尋找外部合作機會？

Terence, thank you. Great question on the operating margin. As you know, we don't go out on a long-term basis on that. But you also know that we intend to continue to be a top-performing biopharma firm when you look at any number of financial metrics and importantly, operating margin.

特倫斯，謝謝。關於營業利益率的問題問得很好。如你所知，我們不會對此進行長期預測。但你也知道，無論從哪個財務指標來看，尤其是營業利潤率，我們都致力於繼續維持生物製藥公司中的佼佼者地位。

I do want to make sure that I mention and confirm, we will remain flexible and adaptable as attractive internal and/or external investment opportunities arise. We have the underlying objective to grow our volumes and after tax cash flow. So that's really important to us. We are committed to lean on our permanent productivity commitment. As I mentioned, we're investing in and working on digitization and automation. So we'll continue to exercise all that muscle to make sure that we do remain a top-performing biopharma firm and operating margin.

我想再次強調，我們將保持靈活性和適應性，隨時抓住有吸引力的內部和/或外部投資機會。我們的根本目標是提升銷售量和稅後現金流，這對我們至關重要。我們將始終致力於提高生產力。正如我之前提到的，我們正在投資並推動數位化和自動化。我們將繼續全力以赴，確保我們保持生物製藥公司領先地位和卓越的營運利潤率。

On the biosimilars, that's a fair question. We continue to see biosimilars as an extremely strong allocation of capital for us. The margins continue to be very competitive. And we're very confident in terms of allocating capital to that category, and we'll continue to do that. And we think we've got some strong expertise there. I like to quote Murdo, who says that we've played a lot of defense in biosimilars. And now as we're on offense, we're able to have a high-quality of execution level. So good questions in that, and I'll flip it over to -- I think to Bob.

關於生物類似藥，這是一個很好的問題。我們仍然認為生物相似藥是我們資本配置中非常重要的領域。利潤率一直都非常有競爭力。我們對在該領域配置資本充滿信心，並且會繼續這樣做。我們認為我們在該領域擁有強大的專業知識。我想引用默多的話，他說我們在生物相似藥領域一直處於被動防守的狀態。現在我們轉守為攻，能夠實現高品質的執行。所以，這是一個很好的問題，接下來我想把問題交給──我想是鮑伯。

Terence, thanks for the question. As I said in my remarks, rather than calling it targeted protein degradation, we're describing it as our induced proximity platform. The intention there, as I said, is just to be clear that we think the technology that we're building can be used not just to degrade proteins but other molecules as well. So we're excited about it. This is -- as I said, again, in my remarks, long-term research strategy. And Dave and his team and I spent a lot of time with each other, trying to think about how to position for the long term.

特倫斯，謝謝你的提問。正如我剛才所說，我們沒有稱之為靶向蛋白降解，而是將其描述為誘導鄰近平台。正如我所說，這樣做的目的是為了明確我們認為我們正在開發的技術不僅可以用於降解蛋白質，還可以用於降解其他分子。所以我們對此感到非常興奮。正如我剛才再次強調的，這是一項長期的研究策略。戴夫和他的團隊以及我花了很多時間在一起，思考如何為這項技術制定長期發展策略。

And in this area, will be both internal and external. I'd remind you that we acquired new evolution now 2 years ago for the purpose of helping to build out this set of capabilities. And I would imagine we'll continue to look, as I said, both internally and externally. Dave, feel free to jump in and add your thoughts.

在這個領域，我們將同時關注內部和外部資源。我想提醒各位，兩年前我們收購了新進化公司，目的就是為了幫助我們建構這套能力。正如我所說，我想我們還會繼續從內部和外部兩個方面進行探索。戴夫，歡迎你隨時補充你的想法。

Yes. I think that covers it pretty well, Bob. I would say that we view this multi specificity in drugs as part of the future. Many of you know that 80% to 85% of the currently desirable targets are currently undruggable. We think this is going to be a very important technology and making many of those targets tractable. And as Bob mentioned, we are investing, for the long haul, we expect that to be a combination of both internal and external innovation.

是的，鮑勃，我覺得你說得很清楚了。我認為藥物的多標靶特性是未來的發展方向。你們很多人都知道，目前80%到85%的理想標靶都無法成藥。我們認為這項技術將非常重要，它能夠使許多這樣的標靶變得可成藥。正如鮑伯所提到的，我們正在進行長期投資，我們預計這將是內部和外部創新相結合的結果。

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。

Great. Dave, I was wondering if you could just comment a little bit more on the BiTE programs and some of the, I guess, safety issues that have happened? And just what's your confidence in those programs, especially as it seems to relate to some of these extended half-life programs?

好的。戴夫，我想請你再詳細談談BiTE計畫以及一些安全問題？你對這些項目有多大信心？特別是考慮到它們似乎與某些延長半衰期項目有關？

I would say, overall, I feel very bullish on the BiTE program. As we mentioned, AMG 160 and AMG 757 are advancing quite rapidly. Cytokine Release Syndrome is clearly the single challenge that sits before the entire field. And we're making adjustments in the 701 program to handle that. I'm quite confident that we can come up with a clinically important profile for that molecule. There are many BCMA molecules in development. And of course, we'll shape our investments according to whether we can really fulfill an unmet medical need.

總的來說，我對BiTE專案非常看好。正如我們之前提到的，AMG 160和AMG 757的進展相當迅速。細胞激素釋放症候群顯然是整個領域面臨的唯一挑戰。我們正在對701項目進行調整以應對這項挑戰。我很有信心，我們能夠為該分子找到具有臨床意義的標靶。目前還有許多BCMA標靶分子正在研發中。當然，我們會根據能否真正滿足未被滿足的醫療需求來調整我們的投資方向。

I would say in closing that I'm quite optimistic about the half-life extended BiTE platform, the -- a few of the positives such as AMG 673 for acute myelogenous leukemia. We're done on purpose because we selected the first generation molecule, which we are investigating in a minimal residual disease setting where that technology is well suited. This was done in close concert with our investigators, many of these choices were part of our strategy. We anticipated making these choices as part of prudent shaping of our portfolio going forward.

最後我想說，我對半衰期延長的BiTE平台相當樂觀，其中一些積極成果包括用於治療急性髓性白血病的AMG 673。我們之所以這樣做，是因為我們選擇了第一代分子，並且正在微小殘留病灶的治療環境中進行研究，而這項技術在這種環境中非常適用。我們與研究人員密切合作，做出了這些選擇，其中許多選擇都是我們策略的一部分。我們預料到這些選擇是未來審慎建構產品組合的一部分。

So overall, I feel quite good about where we are and how that platform is evolving.

總的來說，我對我們目前的狀況以及平台的發展方向都感到非常滿意。

Your next question is from Yaron Werber with Cowen.

下一個問題來自 Cowen 公司的 Yaron Werber。

David, I have a question for you, if you don't mind, and a quick follow-up. On sotorasib, can you give us a sense, obviously, it's encouraging that the MEK combo, you're able to get the full dose of sotorasib? Any comments on KEYTRUDA, SHIP2 or ERBITUX? And then on tezepelumab, the late-breaker looks really good. The data in the steroid-refractory was surprising, and I'm not sure if it's potentially trial design differences from the other biologics, just given how robust the response is otherwise. Would you consider repeating that study with a more similar trial design for the other ones?

David，如果您不介意的話，我有個問題想問您，還有一個後續問題。關於索托拉西布（sotorasib），您能否談談您的看法？顯然，MEK聯合療法能夠達到索托拉西布的全劑量，令人鼓舞。您對KEYTRUDA、SHIP2或ERBITUX有什麼看法？另外，關於tezepelumab，最新公佈的數據看起來非常好。在類固醇難治性患者中的數據令人驚訝，我不確定這是否可能是由於與其他生物製劑的試驗設計不同造成的，因為其他患者的反應都非常穩定。您是否考慮過採用更相似的試驗設計重複這項研究，以評估其他患者的療效？

Yes. Thanks for the questions. In regards to the combinations, the ones you mentioned are all actively in dose escalation, looking at either different doses or in some cases, even scheduling, depending on the agents. This is standard Phase Ib oncology drug development.

是的，謝謝您的提問。關於合併用藥，您提到的那些方案目前都在積極進行劑量遞增試驗，我們會根據具體藥物調整劑量，甚至在某些情況下調整給藥方案。這是腫瘤藥物Ib期臨床試驗的常規流程。

I feel good about how quickly we're moving. And we'll provide guidance as we expect those data to emerge. With tezepelumab, as you mentioned, the abstract is out now. We feel the data are very strong. We feel we're competitive. With the best in the high eosinophil population and in many ways, stand-alone in the low eosinophil population, the steroid-sparing study.

我對我們的進展速度感到滿意。我們會根據預期數據提供指導。正如您所提到的，tezepelumab 的摘要已經發布。我們認為數據非常有力，具有競爭力。在嗜酸性粒細胞增多症患者中，我們取得了最佳成果；在嗜酸性粒細胞減少症患者中，我們的類固醇替代研究在許多方面也獨樹一幟。

As you alluded, we think there were potentially trial design issues. And we're going through that with our investigators, anticipate presenting those data a little later this spring. And we're discussing with our partners, whether a differently designed follow-on study would be appropriate.

正如您所提到的，我們認為試驗設計可能有問題。我們正在與研究人員一起探討這些問題，預計將在今年春季稍後公佈相關數據。我們也正在與合作夥伴討論，是否需要進行一項設計不同的後續研究。

I would point out that, that trial was not necessary for filing and we are moving ahead with all deliberate speed as we announce with global submissions of tezepelumab based on the current data.

我想指出的是，該試驗並非提交申請的必要條件，我們將根據現有數據，以最快的速度推進tezepelumab的全球申請。

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。

Peter, I may have missed this, but looking to 2021 revenue guidance, can you speak at a higher level, what contribution, if any, you assume from sotorasib and tezepelumab for this year? And are there any COVID headwinds still factored in when you look at product sales? Or do you assume 2021 as a more normalized demand curve all year?

Peter，我可能錯過了相關信息，但關於2021年的收入預期，您能否從更高的層面談談，您預計sotorasib和tezepelumab今年的收入貢獻是多少（如果有的話）？您在考慮產品銷售時，是否仍將新冠疫情帶來的不利影響納入考量？或者您認為2021年全年的需求曲線會更加正常？

Thanks for the question, Geoff, and I'll invite Murdo here just a moment to jump in on soto and teze. And look, we expect continued COVID impact throughout 2021 and revenue potential recovery in the latter part of the year contingent on the vaccination rollout, as I mentioned. So we'll be closely monitoring that, as you can imagine. And with respect to soto and teze, let me turn that over to Murdo.

謝謝你的提問，Geoff。我請Murdo稍作發言，談談soto和teze。正如我之前提到的，我們預計新冠疫情的影響將持續到2021年全年，收入復甦的可能性取決於疫苗的推廣，時間可能在下半年。所以，我們會密切關注疫苗的推廣情況。至於soto和teze，現在就交給Murdo來談談吧。

And look, it's a very exciting time for us. And we've invested a lot of money preparing the launches for those and so forth. So Murdo?

你看，這對我們來說是一個非常令人興奮的時刻。我們投入了大量資金來準備這些發表會等等。那麼，默多？

Thanks, Peter, and thanks for the question, Geoff. Obviously, we're quite excited about sotorasib. And I want to compliment Dave and his team how fast they've moved in developing this product and also just the number of regulatory submissions, they've been able to affect in a very compressed time frame. So we are optimistic and hopeful that we'll get a fairly quick review in multiple markets around the world. And so we would expect sotorasib to contribute to revenue. We don't give product-specific guidance, but this is a very large population of high unmet medical need. There's not a lot of choice for these advanced non-small cell lung cancer patients. So we do anticipate that there'll be a potential market with a high need there.

謝謝Peter，也謝謝Geoff的提問。顯然，我們對sotorasib這款產品非常興奮。我要讚揚Dave和他的團隊，他們在產品研發方面進展神速，而且在如此短的時間內提交的監管申請數量也相當驚人。因此，我們樂觀地認為，sotorasib能夠在全球多個市場迅速獲得批准。我們也期待sotorasib能夠帶來營收成長。我們不提供針對特定產品的業績預測，但目前存在著大量未被滿足的醫療需求。對於這些晚期非小細胞肺癌患者來說，治療選擇非常有限。因此，我們預期這方面存在著巨大的潛在市場需求。

The one caution that I'll put out is just the actual percentage of advanced non-small cell lung cancer patients that have a KRAS G12C status result in their file and their medical record. Right now, we ascertain that to be at about 50%. So we've got work to do to grow that number. And obviously, we've seen with other targeted therapies. When you have an actionable mutation, the testing rate rises fairly rapidly. So we would expect upon approval to be able to do that.

我唯一要提醒的是，在目前晚期非小細胞肺癌患者中，KRAS G12C 狀態檢測結果的實際比例約為 50%。因此，我們需要努力提高這一比例。顯然，我們已經看到，在其他標靶療法中，一旦發現可標靶的基因突變，檢測率就會迅速上升。所以我們預計，一旦該療法獲得批准，檢測率也會隨之提高。

But nonetheless, we think sotorasib will be a meaningful contribution to at least revenue in the U.S. And then teze, we'll see what the regulatory authorities do with the filing, obviously, given that we had Breakthrough Designation. And obviously, given the pan-eosinophilic results that we've seen, and now you guys can see the breakdown in that in the abstract. We think this is an important medicine to get to market very quickly.

但即便如此，我們認為索托拉西布至少在美國將對公司營收做出顯著貢獻。接下來，我們也要看看監管機構會如何處理這份申請，畢竟我們已經獲得了突破性療法認定。而且，鑑於我們已經看到了泛嗜酸性粒細胞性貧血的療效，現在你們可以在摘要中看到詳細的分析結果，我們認為這是一種非常重要的藥物，應該盡快推向市場。

The last question you asked about COVID, in fact, Geoff, was just -- I think we actually anticipate COVID will have a fairly significant impact on the market through the better part of the year, beyond the midpoint of the year. I hope we're wrong, and I hope that vaccination programs will improve. But right now, we think that COVID will be with us for the majority of 2021.

傑夫，你上次問的關於新冠疫​​情的問題，其實是——我認為我們預計新冠疫情將在今年大部分時間裡，甚至到年中之後，對市場產生相當大的影響。我希望我們的判斷是錯誤的，也希望疫苗接種計劃能夠有所改進。但就目前而言，我們認為新冠疫情將在2021年的大部分時間與我們共存。

Your next question is from Evan Seigerman with Crédit Suisse.

下一個問題來自瑞士信貸的埃文·塞格曼。

So I want to ask one on business development and capital allocation priorities. So it seems like there's a growing need for more mid-stage assets, noting several pipeline pauses reported in this quarter. With 80% of free cash flows going to dividends and repurchases, how do you think about bringing in larger scale assets? And would you lever up beyond your current leverage levels if there was an attractive opportunity?

我想問一個關於業務拓展和資本配置優先事項的問題。鑑於本季度報告的幾個在建項目暫停，似乎對中期資產的需求正在增長。由於80%的自由現金流都用於分紅和股票回購，您如何看待引進更大規模的資產？如果遇到有吸引力的機會，您會考慮提高槓桿嗎？

Evan, I think we've been pretty consistent in saying that our focus is on investing in the business. So as we said in our prepared remarks, we're planning to increase our investment in R&D this year. So committing internally to continue to allocate capital to R&D opportunities.

埃文，我認為我們一直以來都很強調，我們的重點是投資業務發展。正如我們在準備好的演講稿中所說，我們計劃今年增加研發投入。因此，我們內部承諾將繼續把資金分配給研發機會。

We'll continue to look externally. We'll look at small and larger opportunities like licensing and business development. They're very active in the areas where we have demonstrated expertise therapeutically. And that's what our focus very likely entail in opportunities that sit well with the areas that we have demonstrated expertise in.

我們將繼續關注外部機遇，包括許可授權和業務拓展等各種規模的機會。這些公司在我們已展現出治療專長的領域中非常活躍。因此，我們未來的發展重點很可能就在於尋找與我們已展現專長的領域相契合的機會。

And in terms of the balance sheet, rather than engage in hypothetical, we maintain a strong balance sheet so that we have strategic flexibility. And we'll consider individual opportunities as they arise.

至於資產負債表方面，我們不搞假設性分析，而是保持穩健的資產負債表，以確保策略彈性。我們會根據具體情況考慮各種機會。

Your next question is from Dane Leone with Raymond James.

您的下一個問題來自 Raymond James 的 Dane Leone。

Congratulations on the update and outlook for 2021. So the question for me, it focuses a bit on tezepelumab, but is a little bit different than what's been discussed previously. Allergy and asthma, specifically, in this case, would be a new vertical for Amgen. How are you thinking about building out that vertical around expected commercial launch of tezepelumab, but also thinking about other indications or assets behind that internally or externally that you could point to, to make it more of a broader vertical going forward.

恭喜您更新了2021年的業績展望。我的問題雖然也與tezepelumab有關，但與之前討論的內容略有不同。具體來說，過敏和氣喘將是安進公司的一個新業務領域。您打算如何圍繞tezepelumab的預期商業上市來擴展這一業務領域？同時，您能否也考慮公司內部或外部的其他適應症或相關資產，以便將其發展成為更廣泛的業務領域？

In that same vein, maybe touch a little bit more on oncology. Obviously, in the solid tumor space, it hasn't been an area that you've been heavily invested in historically, but obviously, with sotorasib approval coming in the first half this year. You're kind of resting on the BiTE program behind that.

同樣地，或許可以再多談談腫瘤學方面。顯然，在實體瘤領域，你們過去並沒有投入太多精力，但隨著索托拉西布（sotorasib）今年上半年獲批，你們現在主要依靠的是其背後的BiTE計畫。

Are there other assets outside the BiTE program that you could highlight internally that might expand your presence there? And/or should we be thinking about something more differentiated that you might do externally around the solid tumor space?

除了BiTE專案之外，您是否還有其他可以向內部重點介紹的資源，以擴大您在該領域的影響力？或者，我們是否應該考慮您在實體腫瘤領域可以進行的更具差異化的項目？

There's a lot there, Dane, in your question. Murdo and I will just double team. But very quickly, let me remind you what we pointed out when we entered into a partnership with AstraZeneca, in particular, around the respiratory opportunity, which was that this that you point out, is a new area for us. We felt that we could deliver more for our shareholders and more for patients by collaborating with a group that had demonstrated expertise in respiratory medicine. And so we chose to partner with AstraZeneca, and we're pleased with that collaboration and look forward to taking the molecule to market with them.

丹恩，你的問題資訊量很大。我和默多會一起探討。不過，我先簡單回顧一下，當初我們與阿斯特捷利康建立合作關係時，尤其是在呼吸系統領域，我們特別強調了這一點。你提到的這個領域對我們來說是一個全新的領域。我們認為，與一家在呼吸系統藥物領域擁有豐富經驗的公司合作，能夠為我們的股東和患者帶來更多價值。因此，我們選擇了與阿斯特捷利康合作，我們對這次合作感到非常滿意，並期待與他們攜手將這款藥物推向市場。

And I would just point out that we came to this through our commitment to anti inflammation. Have decades of experience in the biology of information that we've been able to capitalize on with this program and hopefully, others over time. But Murdo, jump in and in particular, share your thoughts also on the solid tumor question.

我想指出的是，我們之所以能取得今天的成就，是因為我們致力於抗發炎研究。我們在生物學資訊領域擁有數十年的經驗，並已將其應用於這個項目，希望未來也能應用於其他項目。穆爾多，請您也談談您對實體瘤問題的看法。

Yes, sure. We -- thanks, Bob. We are building out our teams as we speak. And Amgen will help commercialize tezepelumab in the Americas region. So U.S. and Canada, we will be focused on allergists, while AstraZeneca will play a broader role beyond just allergists, including the respiratory specialties. So this is, as you mentioned, it's a new area, but it's not that different from what we've done, as Bob mentioned, in other inflammatory disease processes. The other thing that's worth mentioning is we'll be taking a leading role in establishing access for tezepelumab with payers. And again, our extensive biologics contracting experience in Part D and the government programs will help us secure broad access for tezepelumab for a broad range of patients. As you saw, we have a nice product profile here that will benefit a lot of patients regardless of their eosinophilic status.

是的，當然。謝謝，鮑伯。我們正在組建團隊。安進將協助我們在美洲地區推廣tezepelumab。在美國和加拿大，我們將專注於過敏專科醫生，而阿斯特捷利康的作用範圍將更廣，不僅限於過敏專科醫生，還包括呼吸專科醫生。正如您所說，這是一個新領域，但與我們在其他發炎性疾病領域所做的工作並沒有太大區別，正如鮑勃所提到的。另一點值得一提的是，我們將在與支付方協商tezepelumab的准入方面發揮主導作用。此外，我們在D部分和政府專案方面豐富的生物製劑合約經驗將有助於我們確保tezepelumab能夠惠及更廣泛的患者群體。正如您所看到的，我們的產品特性良好，無論嗜酸性粒細胞狀態如何，都能使許多患者受益。

And then Dave Reese's team is obviously building out medical capabilities for the same customer-facing group. So we're excited about it. It's a focused effort. The beauty of focusing on allergist is they're very productive prescribers, but they're a relatively small audience size. So we'll be quite focused on addressing that.

戴夫·里斯的團隊顯然也在為同一客戶群建立醫療功能。我們對此感到非常興奮。這是一項重點突出的工作。專注於過敏科醫生的優勢在於，他們的處方量非常大，但受眾群體相對較小。因此，我們將集中精力解決這個問題。

When it comes to kind of how we're looking at our oncology portfolio, we've got a very strong base right now in oncology between our hematology business, our solid tumor therapeutics that we have now, our overall biosimilar portfolio and our supportive care, basically 1 in 5 oncology patients today receives an Amgen therapy. And so bringing sotorasib into that mix and then the potential of AMG 160 and 757 and 701, I think, is a fairly action-packed next few years in oncology that we can build on the current strength that we have, and we're excited about that.

就我們目前在腫瘤領域的業務組合而言，我們擁有非常強大的基礎，這體現在我們的血液疾病業務、現有的實體腫瘤治療藥物、整體生物相似藥產品組合以及支持治療方面。基本上，目前每5名腫瘤患者中就有1名接受安進的治療。因此，將sotorasib納入其中，再加上AMG 160、757和701的潛力，我認為未來幾年我們在腫瘤領域的發展將非常蓬勃，我們可以在現有優勢的基礎上更進一步，對此我們感到非常興奮。

I'm always asking Dave Reese to deliver more, and I know his team have a lot of other earlier assets to put into the clinic. I'll turn it over to Dave for additional comments.

我一直要求戴夫·里斯拿出更多成果，我知道他的團隊還有很多早期的素材可以投入臨床研究。接下來請戴夫補充說明。

Yes. Exactly. We've got a couple of gastric cancer BiTEs, of course, also a solid tumor indication. And we've got some other molecules in late preclinical we're just entering the clinic that will target solid tumor indications. More on those as we're ready to speak about them going along. So I think it's going to be quite a broad portfolio.

是的，沒錯。我們有一些針對胃癌的BiTEs，當然也有一些針對實體腫瘤的適應症。此外，我們還有一些處於臨床前後期階段的分子，即將進入臨床試驗，這些分子也將用於治療實體腫瘤。我們會根據情況，在適當的時機再詳細介紹這些分子。所以我認為，我們的產品組合將會非常廣泛。

Your next question is from Robyn Karnauskas with Truist Securities.

下一個問題來自 Truist Securities 的 Robyn Karnauskas。

So I have a question for Murdo. I was just looking at the MVASI strength and the KANJINTI decline and the Neulasta price decline was significant. Putting all these trends together, can you just help us think now what you think of how to model the tail for biosimilars? And if there's differences between some of your oncology drugs like the strength of MVASI is really impressive versus the decline of Neulasta. Just give a sense of how we should think about that and help us model that.

我有個問題想問Murdo。我剛剛在看MVASI的強勢表現、KANJINTI的下滑以及Neulasta價格的顯著下降。綜合所有這些趨勢，您能否幫我們思考一下，您認為應該如何對生物相似藥的尾部進行建模？另外，您提到的某些腫瘤藥物之間存在差異，例如MVASI的強勢表現非常顯著，而Neulasta的下滑則非常明顯。請您就此給予一些思路，幫助我們進行建模。

Thanks for the question, Robyn. And as we look at 2021, I would say that the majority of our growth will come from additional international launches of our biosimilar portfolio. And obviously, some additional revenue from AVSOLA and RIABNI, 2 relatively recent biosimilar launches in the U.S. Specifically, if you think about MVASI and KANJINTI, they are a little bit different. And the differences are twofold. There's more than that ballistic to the 2 major ones. Bevacizumab as a molecule is actually growing, whereas trastuzumab as a molecule is flat to declining. So one thing that we're seeing in MVASI is actually the number of cycles of bevacizumab overall is growing. And so even holding share in that molecule actually holds up quite well. We also have less competition. That's the other factor.

謝謝你的提問，Robyn。展望2021年，我認為我們的大部分成長將來自生物相似藥產品組合在國際市場的進一步上市。當然，AVSOLA和RIABNI這兩款相對較新的生物相似藥在美國的上市也將帶來一些額外收入。具體來說，MVASI和KANJINTI的情況略有不同，主要體現在兩個方面。除了這兩款主要藥物的爆發式增長之外，還有更多因素。貝伐珠單抗作為一種分子，其市佔率實際上正在成長，而曲妥珠單抗作為一種分子，其市佔率則持平甚至下降。因此，我們在MVASI方面看到的一個特點是，貝伐珠單抗的整體治療週期數正在增長。所以，即使目前僅維持貝伐珠單抗的市場份額，也相當不錯。此外，我們的競爭也相對較小，這是另一個有利因素。

So there's less competition for now in the bevacizumab molecule, whereas with trastuzumab, we have more competitors. And so I think going forward, you would see competitive dynamics shaping those 2 brands a little bit differently.

所以目前貝伐珠單抗的競爭較小，而曲妥珠單抗的競爭對手則較多。因此，我認為未來這兩種品牌的競爭格局會略有不同。

Your next question is from Mohit Bansal with Citigroup.

下一個問題來自花旗集團的莫希特·班薩爾。

Congrats on all the progress. Maybe one question on EVENITY. It seems like you have been able to grow this product, but not just U.S., globally as well. And this has been a difficult market historically. So could you please help us characterize the growth in terms of whether you are taking share from existing anabolics or you're expanding the market? And then do you expect any challenge when the path from the comes to market or for this product?

恭喜你們取得的所有進展。關於EVENITY，我有一個問題。你們似乎成功地發展了這款產品，而且不僅在美國，在全球範圍內也是如此。要知道，這個市場歷來競爭激烈。所以，能否請你們解釋一下，你們的成長是基於從現有合成代謝類固醇產品手中搶佔市場份額，還是在拓展市場？另外，你們預計這款產品在上市過程中會遇到哪些挑戰？

Yes. I was picking up a little bit of static. So I think the question's on EVENITY. The first part of the question I understood was how are we sourcing our EVENITY growth? Is it from existing anabolic patients? Or are we expanding and treating new patients? I didn't catch the second part of the question, but let me address the first part.

是的，我聽到了一些雜音。所以我覺得問題是關於EVENITY的。我理解的第一部分問題是：EVENITY的成長來源是什麼？是來自現有的合成代謝患者嗎？還是我們在擴大規模，治療新患者？我沒聽清楚問題的第二部分，但我先回答第一部分。

Overall, we're pleased with how EVENITY has evolved. We've got nice evolution in our Japan business. In Japan, it's obviously -- we've been in the market a little bit longer. So one thing that we're seeing with EVENITY is patients are on the product for a 12-month duration of treatment. And so you have to replenish those new patients. You do have to source those new patients. And so I think the team in Japan is quite experienced now at sourcing new patients and not necessarily where we got our early growth was from which was switching from other anabolics.

總體而言，我們對 EVENITY 的發展感到滿意。我們在日本的業務發展良好。在日本，我們進入市場的時間顯然更長一些。我們觀察到，EVENITY 的一個特點是患者需要接受為期 12 個月的療程。因此，我們需要不斷補充新患者。我們需要尋找新的患者群體。我認為，日本團隊現在在尋找新患者方面經驗豐富，而這與我們早期成長的來源（即患者從其他合成代謝類固醇藥物轉換而來）有所不同。

And there are -- unfortunately, there are a lot of aging patients in these markets where osteoporosis goes unchecked and patients suffer fractures and these high-risk patients need a solid bone builder like EVENITY to be able to improve their clinical outcomes.

不幸的是，在這些市場中有很多老年患者，他們的骨質疏鬆症得不到控制，導致骨折，這些高風險患者需要像 EVENITY 這樣可靠的骨骼構建劑來改善他們的臨床結果。

So I think in Japan, we're sourcing now more de novo growth than we were perhaps 6 to 12 months ago. Whereas in the U.S., it's much more of a mix of de novo and switch, the other thing that's helping us in the U.S. is, of course, having both Prolia and EVENITY for the customer. A lot of the time when a patient will come in and have a fracture despite their Prolia treatment, they're a really good candidate for EVENITY. So we're often getting patients on both treatments.

所以我覺得在日本，我們現在的新病例比6到12個月前還要多。而在美國，新病例和轉換病例則較為混合。當然，在美國，我們同時擁有Prolia和EVENITY這兩種治療方案也對我們有幫助。很多時候，患者即使接受了Prolia治療後仍出現骨折，但其實非常適合接受EVENITY治療。因此，我們經常會遇到同時接受這兩種治療的患者。

And sometimes after the 12 months of EVENITY treatment are up, they'll roll back on to Prolia. So it's a nice franchise to have and have both an anti-resorptive and a bone-building agent for our customers. So I think the future growth looks very good. Obviously, our partners at UCB are just getting going in Europe as they establish reimbursement for the product. But I'm quite excited about what EVENITY could become for these -- for bone-building for these very high-risk post fracture patients.

有時，在完成12個月的EVENITY療程後，患者會重複使用Prolia。因此，能夠同時為我們的客戶提供抗骨吸收劑和骨生成劑，這確實是一個不錯的選擇。所以我認為未來的成長前景非常樂觀。當然，我們的合作夥伴UCB在歐洲的業務才剛起步，他們正在努力爭取該產品的健保報銷。但我對EVENITY在這些高危險群骨折患者的骨生成方面所能取得的成就感到非常興奮。

Your next question is from Umer Raffat with Evercore ISI.

您的下一個問題來自 Evercore ISI 的 Umer Raffat。

Murdo, you recently mentioned 25,000 as the target population for KRAS. And that sounded rather high to me, at least for U.S. So I was curious, a, whether that was for U.S.-only or worldwide? And b, if you were assuming a, around 14% prevalence rate for G12C and whether you were doing this analysis on non-squamous only for this math.

Murdo，你最近提到KRAS的目標族群是25,000人。我覺得這個數字相當高，至少對美國來說是這樣。所以我很好奇，a）這個數字是指美國還是全球？ b）如果你假設a，G12C的盛行率約為14%，那麼你在計算時是否只考慮了非鱗狀細胞癌？

Yes. Thanks for the question, Umer. The 25,000 was a U.S. number. We actually estimate the non-small cell lung cancer incidents globally at 120,000 patients.

是的。謝謝你的提問，烏默。 25000這個數字是美國的。實際上，我們估計全球非小細胞肺癌的新病例約為12萬例。

Now obviously, there's some reduction from first-line to second-line in lung cancer because, unfortunately, we lose patients in frontline. The second line and beyond is obviously our target population at launch. And we assume a 13% incidence of KRAS G12C in the broad non-small cell lung cancer patient population.

顯然，肺癌一線治療到二線治療的患者數量有所減少，因為不幸的是，第一線治療的患者往往會死亡。二線及以後的治療顯然是我們產品上市時的目標族群。我們假設在非小細胞肺癌患者族群中，KRAS G12C突變的發生率為13%。

Right. So Murdo, if we just go down that track, 13% of 120,000. I was just confused, the 25,000?

沒錯。所以，默多，如果我們照這個思路算，那就是12萬的13%。我剛才有點困惑，那2.5萬是什麼意思？

Yes. So that's a U.S.-only number for incidence of non-small cell lung cancer that have progressed into second line and beyond.

是的。所以這是僅針對美國的非小細胞肺癌進展到第二線及以上治療階段的發生率數據。

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 for Dave, maybe it's the BiTEs that you spoke to previously, but I always want to ask you this question. Within the early-stage Phase I or stage 2 pipeline, what are you most excited about in 2021? What's going to be the next sotorasib?

或許對Dave來說，或許對你來說，是你之前接觸過的BiTEs，但我一直想問你這個問題。在早期I期或II期研發管線中，你對2021年的哪些專案最感興趣？下一個sotorasib會是什麼？

Yes, thanks, and I think we are able to just rejoin in time for that question. Again -- I think in terms of the early pipeline, AMG 160 and AMG 757, as I highlighted in my prepared remarks, are ones that we're really looking at. 160 has advanced into the expansion cohort. And if we continue to generate data as we have recently through a larger number of patients. That's a program that we would probably be discussing potential registration paths sooner rather than later. I think AMG 757 is just one step behind. And that's another one that we're keeping a very close eye on. And then in our inflammation portfolio, we've got a variety of Phase II assets in autoimmune indications, as we previously indicated, and those programs are ones that I'm quite interested in, as we move forward.

是的，謝謝。我想我們正好可以及時回到討論環節，回答這個問題。再次強調－就早期研發管線而言，正如我在準備的演講稿中提到的，AMG 160 和 AMG 757 是我們重點關注的項目。 AMG 160 已經進入擴充佇列。如果我們能像最近一樣，透過更多患者獲得數據，那麼我們可能很快就會討論該計畫的潛在註冊途徑。我認為 AMG 757 也緊隨其後，我們也密切關注它的進展。此外，在我們的發炎產品組合中，正如我們之前提到的，我們擁有多種針對自體免疫疾病的 II 期臨床試驗項目，這些項目也是我非常感興趣的，我們會繼續前進。

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 appreciate the question. Murdo, a question about your commercial model. You mentioned in the prepared remarks a couple of times that you were shifting to more of a digital approach. And I'm just wondering, we've heard that there have been significant reductions in your commercial field organizations. Can you give us a sense of what the magnitude of the efficiency in head count you're seeing on your average sales force by moving towards digital? And could you talk about how you think that might play out in a post-COVID world? Wouldn't you expect to have to ramp back up once we eliminate social distancing?

感謝您的提問。默多，關於您的商業模式，我有個問題。您在準備好的發言稿中多次提到，你們正在轉向更數位化的模式。我們聽說你們的銷售團隊規模已經大幅縮減。您能否簡單介紹一下，轉向數位化後，你們的銷售團隊在人員配置方面平均能獲得多大的效率提升？您能否談談在後疫情時代，這種模式會如何發展？一旦我們取消社交隔離，您是否預計需要重新擴大規模？

Thanks, Geoffrey, for the question. There were a couple of factors that went into our recent reorganization of our field force. One is just portfolio evolution and creating capacity for the new product launches and then reallocating from the older side of the portfolio. And depending on which region you're talking about in the world with Amgen, we're in very different stages of development. So for example, we're placing large investments in field force in Japan and in China, even in Russia and some other markets that are emerging for us as being important growth drivers. And in the U.S., we're really paying close attention to the forces in the market beyond COVID. We're looking at potential negative net price effects and/or price reform, as Bob mentioned in his opening remarks, as being a bit of a prevailing wind here. And so what we're doing is looking at our overall commercial model.

謝謝Geoffrey的提問。我們最近對銷售團隊進行重組主要考慮了幾個因素。首先是產品組合的調整，我們需要為新產品上市騰出資源，並將資源從舊產品組合中重新分配。其次，安進在全球不同地區的業務發展階段也各不相同。例如，我們正在日本、中國、俄羅斯以及其他一些新興市場加大銷售團隊的投入，這些市場對我們來說都是重要的成長動力。而在美國，我們則密切關注新冠疫情后市場的各種因素。正如Bob在開場白中提到的，我們正在關注潛在的淨價格負面影響和/或價格改革，因為這些因素可能會對市場產生重大影響。因此，我們正在重新審視我們的整體商業模式。

And to your point, making it more productive and making it more efficient. So we're largely on track with that plan. We were able to move very rapidly last year and build out our digital capabilities to an even greater extent than we had historically. We are seeing customers willing to engage in those channels. And we think some of those engagements will be persistent beyond COVID, quite frankly, and it's that persistency that we're betting on. What we haven't done is compromised the ability to have competitive share of voice in our field facing interactions, both on the medical side, both on the commercial side, in front of the customer. And so we think we'll continue to be able to compete effectively in the categories we're in as well as augment that with highly efficient digital channels of communication.

正如您所說，提高生產力和效率至關重要。目前，我們的計劃基本上是按部就班地進行。去年，我們迅速推動數位轉型，其能力建構規模甚至超過了以往任何時候。我們看到客戶願意透過這些管道進行互動。坦白說，我們認為其中一些互動即使在疫情結束後也會持續存在，而這正是我們所重視的。我們始終沒有在面向客戶的互動中，無論是在醫療領域或商業領域，都保持著強大的話語權。因此，我們相信我們能夠繼續在現有領域保持有效的競爭優勢，並透過高效的數位化溝通管道進一步增強競爭力。

Our 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。

And congrats on sotorasib data, the impressive execution. I guess, Murdo and Bob, coming back to Otezla. At the time of the acquisition, it seems to have oriented us that the majority of the growth would come from the U.S. and I guess, your comments today seem to be teeing up really, I guess, the global nature of the growth going forward. I guess just your level of confidence around Otezla growth in the U.S. through the mid-2025 time frame, I guess, given the competition and what have you.

恭喜你們公佈了索托拉西布（sotorasib）的數據，執行得非常出色。我想，默多和鮑勃，我們還是回到奧特茲拉（Otezla）的話題。收購之初，我們似乎認為大部分成長將來自美國市場，而你們今天的發言似乎也預示著未來成長將走向全球。我想了解的是，考慮到競爭情勢等等因素，你們對奧特茲拉在美國市場到2025年中期的成長有多大信心？

Maybe I'll just take the first sense or 2, and then Murdo, you can augment however you'd like. But Carter, what I'd say is that when we acquired it, we said we felt we could achieve double-digit growth through the first several years of ownership, and we continue to feel confident in that. And that's a function of both potential for increased label range in the U.S. as well as the opportunity to launch in international markets. But Murdo, maybe you want to elaborate on the opportunity, the mild to moderate, severe opportunity.

或許我先說前兩點，然後默多，你可以隨意補充。卡特，我想說的是，我們收購這家公司時就說過，我們相信在接手後的頭幾年就能實現兩位數的增長，而且我們仍然對此充滿信心。這既得益於我們在美國擴大品牌範圍的潛力，也得益於進軍國際市場的機會。默多，或許你想詳細說這個機遇，從輕微到中等，再到巨大的機會。

Yes. Thanks, Bob. We do see some of the international expansion maturing now. We've got a good business for Otezla in Japan. We're pursuing registration in China, and we recently secured reimbursement in Australia, so we're evolving the global footprint of Otezla beyond where the legacy Celgene efforts had it. So that is one source of growth. But as Bob mentioned, we're also pursuing in the U.S. mild to moderate approval on the basis of the positive data set we have there. And that will allow us to move Otezla into a patient population that really is still an unmet need. These are patients who have enough skin surface area that they might be seeking an alternative to messy and inconvenient topical agents. And I think Otezla can play a very important role there in helping treat those patients. We're also in making investments in Otezla by expanding the promotional footprint of the product to include primary care promotion, something that Celgene had not done historically. So we're doing that both for the moderate to severe patient, but as well for that mild to moderate indication in anticipation of that potential approval.

是的，謝謝，鮑伯。我們確實看到一些國際擴張正在成熟。我們在日本的Otezla業務發展良好。我們正在尋求在中國註冊，並且最近在澳洲獲得了醫保報銷，因此我們正在拓展Otezla的全球業務版圖，超越了Celgene以往的佈局。這是成長的一個來源。正如鮑伯所提到的，我們也在基於我們在美國獲得的積極數據，尋求Otezla在美國的輕度至中度適應症批准。這將使我們能夠將Otezla推廣到目前仍存在未滿足需求的患者群體。這些患者皮膚表面積較大，他們可能正在尋找一種替代繁瑣且不方便的局部用藥的方法。我認為Otezla可以在幫助治療這些患者方面發揮非常重要的作用。我們也增加對Otezla的投資，擴大產品的推廣範圍，包括基層醫療機構的推廣，這是Celgene過去從未涉足的領域。因此，我們這樣做既是為了中度至重度患者，也是為了輕度至中度適應症，以期獲得潛在的批准。

And the only other thing I would say is while we are seeing a little bit of softness in psoriasis and broader rheumatology, for the category due to COVID, Otezla being an oral has held up quite well, and the execution has been strong.

我唯一想補充的是，雖然由於 COVID-19 的影響，銀屑病和更廣泛的風濕病領域出現了一些疲軟，但口服藥物 Otezla 的表現相當不錯，而且執行情況也很好。

I also think that the established safety and efficacy profile of Otezla is highly appreciated, given recent news in the broader rheumatology category of other orals where perhaps that risk-benefit equation is different than it is where it's very strong with Otezla. So we think we've got a good opportunity for growth. We also said when we gave that guidance, it assumed a successful competitive program from the TYK2 asset. And of course, that was confirmed today.

我認為，鑑於近期其他口服風濕病藥物領域的情況，Otezla 已確立的安全性和有效性得到了高度認可。在這些藥物中，風險效益比可能與 Otezla 有所不同，而 Otezla 的風險效益比非常高。因此，我們認為公司擁有良好的成長機會。我們也曾表示，在給予績效指引時，我們假設 TYK2 資產的競爭性項目能夠取得成功。當然，這一點今天也得到了證實。

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。

Congrats on all the progress and thank you for taking the question. Since you received Breakthrough Therapy Designation for sotorasib in China, can you comment on how fast you could submit a filing and gain regulatory approval? And what percent of Asian non-small cell lung cancer patients have the KRAS G12C mutation? And how large is that commercial opportunity is for sotorasib in China?

恭喜你們取得的所有進展，也謝謝你們回答這個問題。既然你們的索托拉西佈在中國獲得了突破性療法認定，能否談談提交申請並獲得監管部門批准需要多長時間？亞洲非小細胞肺癌患者攜帶KRAS G12C突變的比例是多少？索托拉西佈在中國的商業機會有多大？

Thanks, Jay. We're very pleased to get breakthrough therapy designation in China. As our filing plans move forward with our colleagues at BeiGene, we'll provide guidance about what those time lines might look like. It has a little bit different implications in China than it does potentially in the United States.

謝謝Jay。我們非常高興在中國獲得突破性療法認定。隨著我們與百濟神州的同事們推進申報計劃，我們將提供關於時間表的指導。這在中國的影響可能與在美國略有不同。

And then one thing that we're looking at quite carefully is the epidemiology of G12C mutations. There is a suggestion that it may be a little lower in prevalence in Asian populations. Probably because they are mutually exclusive with mutations in EGFR, which are quite high in these populations, up to 40% in China and Japan, for example. So that will be an important question that we address. We've got active research collaborations now looking at just that. And Murdo, I don't know if you want to add anything about the commercial side in China.

我們正在密切關注G12C突變的流行病學。有跡象表明，這種突變在亞洲人群中的盛行率可能略低。這可能是因為G12C突變與EGFR突變互斥，而EGFR突變在亞洲人群中的盛行率相當高，例如在中國和日本高達40%。因此，這將是我們重點關注的問題。我們目前正積極進行相關研究合作。 Murdo，我不知道你是否想補充一些關於中國市場商業的內容。

Yes. I think we're obviously very excited about what we can do with the product, huge unmet medical need. We're seeing that China is an attractive market for specialty products and the fact that sotorasib is an oral. It makes it very accessible. So we will pursue commercialization of sotorasib in China and our affiliate is very excited about that.

是的。我們顯然對這款產品的發展前景感到非常興奮，因為它滿足了巨大的未滿足醫療需求。我們看到中國是一個極具吸引力的特藥市場，而且索托拉西布是口服藥物，這使得它非常容易獲得。因此，我們將繼續推動索托拉西佈在中國的商業化，我們的子公司對此也感到非常興奮。

Your next question is from Colin Bristow with UBS.

下一個問題來自瑞銀集團的柯林布里斯托。

Obviously, seeing the abstract data for tezepelumab, the less than 150 group looks pretty impressive. I was just curious what your level of confidence is in getting a broad label in light of the fact that you didn't test it for statistical significance? Is that something you've discussed with the FDA previously? And I'll keep it short.

顯然，從tezepelumab的摘要資料來看，150例以下族群的療效相當顯著。我只是好奇，鑑於您沒有進行統計學顯著性檢驗，您對廣泛適應症的批准有多大信心？您之前是否與FDA討論過這個問題？我就簡單說幾句。

Yes. Thanks, Colin. This is a question we get frequently. We demonstrated efficacy in -- across a broad range of patients regardless of eosinophil count, I think that's what clinicians will pay attention to. We'll provide guidance as regulatory discussions proceed. I think it's too early, of course, prior to submitting to debate what a potential label would look like. But our view is that, overall, these are very, very strong data pointing to a differentiated product. And I think this is just going to be a really important medicine for patients with severe uncontrolled asthma.

是的，謝謝科林。我們常被問到這個問題。我們已經證實，無論嗜酸性粒細胞計數如何，該藥物對各類患者均有效，我認為這正是臨床醫生會關注的重點。我們會隨著監管討論的進行提供指導。當然，在提交申請之前討論潛在的標籤內容還為時過早。但我們的觀點是，整體而言，這些數據非常有力，顯示這是一款差異化產品。我認為對於重度難治性氣喘患者來說，這將會是一種非常重要的藥物。

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。

Just about biosimilars. You spike my head a little bit talking about increased competition pressure. Is the anticipation that in 2021 the kind of the price decrease in oncology will exit that 10%, 15% decline rate? Is there any reason to expect it? Are the payers coming in and making changes? Or is this just an issue of you would cite the market, it's going to be hard to get 100%.

關於生物類似藥。您提到競爭壓力加劇，這讓我有點困惑。大家預期2021年腫瘤藥物的價格降幅會超過10%或15%嗎？有什麼理由預期會這樣嗎？支付方會介入並做出改變嗎？還是這只是市場因素，很難達到100%的降幅？

Yes, Ronny. I think you definitely see a diminishing rate of return or gain in terms of volume share. You see that in the shape of our uptake curves for both our oncology biosimilars in the U.S. I think that the way, of course, of these products are used, they're largely used in the community setting, about 80% of the usage of both bevacizumab and trastuzumab in a community oncology setting. And those businesses tend to contract on a network-by-network basis. And by now, most of those contracts are set in motion. There's still some incremental opportunity to add to our overall revenue base. But yes, I think the gains on volume will be incremental. And then price trends, as I mentioned in my scripted remarks, will continue to evolve the way we've seen them.

是的，羅尼。我認為銷量份額的成長速度確實在遞減。從我們在美國兩種腫瘤生物相似藥的市場接受度曲線就能看出這一點。當然，這些產品的使用方式主要是在社區醫療機構，貝伐珠單抗和曲妥珠單抗約80%的使用都發生在社區腫瘤科。而這些業務通常是按網路逐一簽訂合約的。現在，大部分合約都已經生效。我們仍然有一些機會來增加整體收入。但是，是的，我認為銷售成長將是漸進的。至於價格趨勢，正如我在事先準備好的演講稿中所提到的，將繼續以我們先前觀察到的方式發展。

Your next question is from Michael Schmidt with Guggenheim Securities.

下一個問題來自古根漢證券的邁克爾·施密特。

I thought it was interesting to hear about some of the early-stage R&D efforts and the comments that were made around the induced proximity platform. Along those lines, I was wondering if you could provide a little bit more insight into progress that may have been made within your human genetics initiative and when or how this initiative may translate into new pipeline products?

我覺得了解一些早期研發工作以及圍繞誘導鄰近平台的相關評論很有意思。基於此，我想請您進一步介紹一下您的人類遺傳學計劃目前取得的進展，以及該計劃何時或如何轉化為新的在研產品？

Yes. Thanks, Michael. With -- in human genetics, as Bob mentioned and as we previously announced, we have collaborations with Intermountain Health and U.K. Biobank that will add up to 1 million participants. We think we'll have the largest database on Earth as these projects move towards completion. And we have broadened our focus on human data to include other omic technologies such as transcriptomics and proteomics really in the belief that in the long term, it will be human data such as these that are most important for drug discovery and development.

是的，謝謝，邁克爾。正如鮑伯所提到的，也正如我們先前所宣布的，在人類遺傳學領域，我們與Intermountain Health和英國生物銀行開展了合作，這將新增多達100萬名參與者。隨著這些項目的推進，我們相信我們將擁有全球最大的資料庫。此外，我們還將人類數據的研究範圍擴大到其他組學技術，例如轉錄組學和蛋白​​質組學，因為我們堅信，從長遠來看，這些人類數據對於藥物發現和研發至關重要。

At the current time, a majority of our non-oncology portfolio assets have genetic support that's either primary or secondary. And we expect over time that, that percentage will simply increase because there's now clear evidence that targets for which there's genetic validation and programs based on them, have a higher rate of success. So more to come but we firmly believe that the era of human data is upon us, and we believe our collection of capabilities is almost unique in the industry. We intend to push that forward. Thanks.

目前，我們非腫瘤產品組合中的大多數資產都已獲得基因檢測支持，無論是直接支持還是間接支持。我們預計，隨著時間的推移，這一比例將繼續增長，因為現在已有明確證據表明，那些經過基因驗證並基於此開展項目的靶點，其成功率更高。未來會有更多進展，但我們堅信，人類數據時代已經到來，我們相信，我們擁有的能力在業界幾乎是獨一無二的。我們將繼續推進這項進程。謝謝。

Your next question is from Salim Syed with Mizuho Securities.

下一個問題來自瑞穗證券的Salim Syed。

Just one from me strategically, high level here, guys. When you think about Amgen here, is it a correct interpretation to say that the interest in hem/onc has gone significantly down and the interest in solid tumors has gone significantly up? And just curious if KYPROLIS has anything to do with that, if that's the correct interpretation?

各位，我這裡想從戰略層面提個問題。說到安進公司，如果血液腫瘤領域的興趣顯著下降，而實體瘤領域的興趣顯著上升，這種解讀是否正確？如果這種解讀正確的話，KYPROLIS（凱普洛利）是否與此有關？

I don't think it is, Salim, but I invite Dave to...

我不這麼認為，薩利姆，但我邀請戴夫…

Yes. So Salim, yes. KYPROLIS, I think, has nothing to do with that. What you're seeing is the natural evolution of a portfolio based on emerging data, and we will expect that to be shaped going forward based on emerging data, of course, and some of the changes we announced today are strategic choices that we had teed up that we anticipated making, and we think it's a prudent portfolio management to make those choices. Let me call out the MCL-1 programs in particular, where we have elected to move forward with the IV formulation. Again, we had anticipated we would choose among those molecules. And given our ability to more precisely control exposures and achieve a therapeutic window in collaboration with our investigators, we made that decision, and we're moving through dose escalation after re-initiation of that program. So no specific conscious choices based on hematology versus solid tumors and more shaping to come as data emerges.

是的。所以，Salim，是的。 KYPROLIS，我認為與此無關。現在您看到的是基於新出現的數據而自然演進的產品組合，當然，我們預計未來也會根據新出現的數據進行調整。我們今天宣布的一些變化是我們事先準備並預料到的策略選擇，我們認為做出這些選擇是審慎的產品組合管理。我特別想提一下MCL-1項目，我們選擇推進靜脈注射製劑的研發。同樣，我們之前就預料到會從這些分子中做出選擇。鑑於我們能夠與研究人員合作，更精確地控制藥物暴露量並達到治療窗口，我們做出了這個決定，並在該計畫重新啟動後進行劑量遞增。因此，我們並沒有基於血液腫瘤或實體腫瘤的特定選擇，未來還會根據數據的出現進行更多調整。

Salim, I would just jump in and say, we had a strong quarter on KYPROLIS in the fourth quarter, given the approval of CANDOR in our first full quarter, promoting it. And we expect to be able to do a nice job of making hem/onc specialists around the world aware of those data in combination with daratumumab. So more growth to come on KYPROLIS, and it's a good story now.

薩利姆，我插一句，鑑於坎多爾在我們上市後的第一個完整季度就獲批，我們第四季度的KYPROLIS表現強勁。我們預計能夠很好地讓全球血液腫瘤專家了解這些數據，尤其是與達雷妥尤單抗合併用藥的情況。因此，KYPROLIS未來還有更大的成長空間，目前來看前景一片光明。

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. Just thinking about sotorasib in Europe, given EMA typically has a higher threshold for approval for single arm studies, can you describe your degree of confidence you'll be able to get approved on this 37% response rate in 10-month DOR?

這裡是Andrew Galler，替Tim發言。我正在考慮在歐洲使用sotorasib，考慮到EMA通常對單臂研究的批准門檻較高，您能否描述一下，您對憑藉10個月DOR中37%的緩解率獲得批准的信心有多大？

Yes, sure. Let me take that question. We filed in the EU, obviously, we've got on ongoing discussions. We'll provide guidance at the appropriate time. We don't speculate on likely time lines or probabilities in terms of regulatory approvals. But I think it is fair to say that regulators around the world do recognize the large unmet medical need in patients with G12C mutations after first-line therapy, and that certainly will be the focus of discussion going forward.

當然可以。讓我來回答這個問題。我們已經在歐盟提交了申請，目前正在進行磋商。我們會在適當的時候提供指導。我們不會對監管審批的可能時間表或機率做出預測。但我認為可以肯定的是，世界各地的監管機構都認識到，一線治療後攜帶G12C突變的患者存在巨大的未滿足醫療需求，這無疑將是未來討論的重點。

Well, thank you. Again, apologies for the fact that we went about 12 minutes over tonight, but we did want to get to all of your questions. So thank you for your interest and your support of the company, and we look forward to seeing you or being back together with you after the end of the first quarter. Thank you.

好的，謝謝。再次為今晚超時12分鐘左右表示歉意，但我們確實想回答大家的所有問題。感謝大家對公司的關注和支持，我們期待在第一季結束後再次見到大家。謝謝。

Thanks, everybody.

謝謝大家。

Ladies and gentlemen, this concludes Amgen's Fourth Quarter 2020 Financial Results Conference Call. You may now disconnect.

女士們、先生們，安進公司2020年第四季財務業績電話會議到此結束。您可以斷開連線了。