美國安進 (AMGN) 2022 Q1 法說會逐字稿

My name is RJ, and I will be your conference facilitator today for Amgen's First Quarter 2022 Financial Results Conference Call. (Operator Instructions) I would now like to introduce Arvind Sood, Vice President of Investor Relations. Mr. Sood, you may now begin.

我是RJ，今天將擔任安進公司2022年第一季財務業績電話會議的主持人。 （操作說明）現在我要向大家介紹投資人關係副總裁Arvind Sood先生。 Sood先生，您可以開始了。

Okay, RJ. Thank you. Good afternoon, everybody, and welcome to our Q1 call. I think our performance in Q1 exemplifies our continued focus on execution while staying on track to deliver against our long-term objectives. So let's get started.

好的，RJ。謝謝。大家下午好，歡迎參加我們第一季電話會議。我認為我們第一季的業績反映了我們持續專注於執行，同時穩步實現長期目標。那麼，我們就開始吧。

Slides have been posted. 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 vary or differ materially.

幻燈片已上傳。小提醒：本次示範將使用非GAAP財務指標，部分內容屬於前瞻性陳述。我們已向美國證券交易委員會（SEC）提交文件，其中列出了可能導致實際業績與預期業績有重大差異的因素。

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？

Okay. Thank you, Arvind, and hello, everyone, and thank you for joining our call. When we last spoke in February, we told you that we'd be focused on execution and that we have a number of opportunities in place that should enable us to deliver long-term attractive growth.

好的。謝謝Arvind，大家好，謝謝各位參加我們的電話會議。我們上次在二月通話時，曾說過我們會專注於執行，並且我們已經掌握了一些機會，這些機會應該能夠幫助我們實現長期的、可觀的成長。

In the first quarter of the year, we executed well on these many opportunities, delivering 6% revenue growth and 15% earnings per share growth. We achieved this performance despite the effects of COVID during the first 2 months of the year, currency headwinds, and of course, net selling price declines.

今年第一季度，我們把握住了眾多機遇，實現了6%的營收成長和15%的每股盈餘成長。儘管今年前兩個月受到新冠疫情的影響，加上匯率波動以及淨售價下降等因素，我們依然取得了這樣的業績。

The innovative brands that we highlighted in February continued to generate strong volume growth in the first quarter, including Repatha, which was up 49%; Prolia, up 10%; EVENITY, up 59%; and Otezla, up 7% as well as several of our oncology products, which also generated attractive volume growth in the quarter.

我們在二月重點介紹的創新品牌在第一季繼續實現了強勁的銷售成長，包括 Repatha（成長 49%）、Prolia（成長 10%）、EVENITY（成長 59%）和 Otezla（成長 7%），以及我們的幾款腫瘤產品，這些產品在本季也實現了可觀的銷售成長。

Our 2 newest innovative medicines, LUMAKRAS and TEZSPIRE, are off to a strong start offering compelling new treatment options for patients suffering from non-small cell lung cancer and severe asthma, respectively. And we're also pursuing significant new indications for both of these products.

我們最新的兩款創新藥物LUMAKRAS和TEZSPIRE取得了良好的開局，分別為非小細胞肺癌和重度氣喘患者提供了極具吸引力的全新治療方案。同時，我們也積極探索這兩款產品的其他重要適應症。

Let me just say, with respect to the 5 high-quality biosimilars we have on the market, that they're performing well and in line with our expectations. As we've noted previously, growth for the portfolio of biosimilar products over time will come through the steady introduction of new products, including the U.S. launch of AMGEVITA, our biosimilar to HUMIRA in January of next year. AMGEVITA is the first of 6 new biosimilars that we expect to launch by the end of the decade.

我想說的是，我們目前市面上已有的5款高品質生物相似藥表現良好，符合我們的預期。正如我們先前提到的，生物相似藥產品組合的成長將透過穩步推出新產品來實現，包括明年1月在美國上市的阿達木單抗（Humira）生物相似藥AMGEVITA。 AMGEVITA是我們預計在本世紀末之前推出的6款新生物相似藥中的第一款。

International growth is an important component of our long-term strategy, and we saw a strong volume growth outside the U.S. of 15% in the first quarter and nearly 30% volume growth in the Asia Pacific region.

國際成長是我們長期策略的重要組成部分，我們在美國以外的地區第一季實現了 15% 的強勁銷售成長，亞太地區的銷售成長接近 30%。

Turning to our pipeline. We're advancing, as you're aware, a number of mid- to late-stage potentially first-in-class opportunities in inflammation, oncology and general medicine while continuing to invest in our innovative marketed brands and biosimilars. Since our business review, we've had important data readouts for LUMAKRAS, Repatha and ABP 654, which is our Phase III biosimilar candidate to STELARA. We have several more data milestones that come through the remainder of the year.

接下來談談我們的研發管線。如您所知，我們正在推進多個處於中後期階段、具有潛在首創價值的發炎、腫瘤和普通內科領域藥物，同時也持續投資於我們已上市的創新品牌和生物相似藥。自上次業務回顧以來，我們已公佈了LUMAKRAS、Repatha和ABP 654（STELARA的III期生物類似藥候選藥物）的重要數據。今年剩餘時間裡，我們還將公佈更多里程碑式的數據。

Looking to the longer term. We continue to thoughtfully invest in an integrated set of discovery research capabilities, including human data and generative biology, as we look to significantly expand the number of targets we can pursue, reduce cycle times and increase the probability of our success.

著眼長遠，我們將繼續審慎投資於一套綜合性的探索性研究能力，包括人類數據和生成生物學，以期大幅增加我們可研究的靶點數量，縮短研發週期，並提高研發成功的機率。

As to our commitment to innovation, we're committed to pursuing the best innovation available, whether it comes through our own efforts or is sourced externally, and our strong balance sheet and cash flows will enable us to continue to invest in innovation both organically and through business development.

至於我們對創新的承諾，我們致力於追求最好的創新，無論這種創新是來自我們自身的努力還是來自外部，我們強大的資產負債表和現金流將使我們能夠繼續透過內部成長和業務發展來投資創新。

Our work to serve patients comes at a time when society is confronting many challenges, and we're doing our part to address these, as we have throughout our history, with a focus in 4 areas: removing barriers that limit equitable access to health care, working toward a more just society, minimizing our environmental impact and ensuring that our actions and culture reflect Amgen values. If you're interested in learning more, our latest environmental, social and governance report was published earlier today and is available on our website.

在社會面臨諸多挑戰的當下，我們致力於服務病人。正如我們一直以來所做的那樣，我們正盡己所能應對這些挑戰，並重點關注以下四個方面：消除限制公平獲得醫療保健的障礙；努力構建更加公正的社會；最大限度地減少對環境的影響；以及確保我們的行動和文化體現安進的價值觀。如果您有興趣了解更多信息，我們今天早些時候發布了最新的環境、社會和治理報告，您可以在我們的網站上查閱。

Before I turn to Peter, let me just thank my Amgen colleagues around the world for their commitment to serving patients and outstanding execution. Now Peter, over to you.

在向彼得提問之前，請允許我感謝安進公司世界各地的同事們，感謝他們對服務患者的奉獻和卓越的執行力。現在，彼得，輪到你了。

Thank you, Bob. We're pleased with our execution and growth this quarter as we drive towards our long-term goal. I will walk through our first quarter financial results before discussing our 2022 guidance. The financial results are shown on Slide 5 of the slide deck.

謝謝鮑勃。我們對本季的執行情況和成長感到滿意，我們正朝著長期目標穩步邁進。在討論2022年業績展望之前，我將先介紹我們第一季的財務表現。財務績效資訊請參閱投影片第5頁。

The first quarter marked another period of solid execution, with year-over-year revenue growth of 6% and non-GAAP EPS growth of 15%. For product sales, strong volume growth of 9% was driven by Repatha, Prolia and EVENITY. Volume growth was partially offset by declines in net selling price and foreign exchange headwinds.

第一季業績表現穩健，營收年增6%，非GAAP每股收益較去年同期成長15%。產品銷售方面，Repatha、Prolia和EVENITY三款產品銷售量強勁成長9%。但淨售價下降和匯率波動部分抵銷了銷售成長。

Our established portfolio comprised of EPOGEN, Aranesp, Neulasta, NEUPOGEN, Sensipar and Parsabiv, generated almost $1 billion of product sales and continues to deliver strong cash flows.

我們成熟的產品組合包括 EPOGEN、Aranesp、Neulasta、NEUPOGEN、Sensipar 和 Parsabiv，創造了近 10 億美元的產品銷售額，並持續帶來強勁的現金流。

Transitioning to our biosimilars, AMGEVITA remains the most prescribed adalimumab biosimilar in Europe. And looking forward, we will leverage this successful experience as we prepare to launch and grow this product in the United States in January of 2023. For MVASI and KANJINTI, as anticipated, we experienced year-over-year declines driven by net selling price reductions, and we expect this trend to continue for these products. Murdo will discuss product sales in more detail in his remarks.

在向生物相似藥過渡的過程中，AMGEVITA 仍然是歐洲處方量最大的阿達木單抗生物相似藥。展望未來，我們將充分利用這項成功經驗，為 2023 年 1 月在美國推出並拓展產品做好準備。如預期，MVASI 和 KANJINTI 的銷售量較去年同期下降，主要原因是淨售價降低，我們預期這一趨勢將持續。 Murdo 將在演講中更詳細地討論產品銷售情況。

Other revenues of $500 million increased 64% year-over-year, primarily driven by our COVID-19 antibody collaboration. First quarter total non-GAAP operating expenses increased 2% year-over-year as we invest in our pipeline, execute product launches and drive digitalization across the company. On a non-GAAP basis, cost of sales as a percent of product sales increased 1.1 percentage points on a year-over-year basis to 16.6%, primarily due to higher direct manufacturing costs, COVID-19 antibody manufacturing costs and increased royalties and profit shares. Non-GAAP R&D spend in the quarter decreased 1% year-over-year.

其他收入達 5 億美元，年增 64%，主要得益於我們與 COVID-19 抗體計畫的合作。第一季非 GAAP 總營運支出年增 2%，主要原因是我們在產品線投資、產品上市以及公司數位轉型方面投入了資金。以非 GAAP 計算，銷售成本佔產品銷售額的百分比年增 1.1 個百分點至 16.6%，主要原因是直接生產成本、COVID-19 抗體生產成本以及特許權使用費和利潤分成增加。本季非 GAAP 研發支出較去年同期下降 1%。

Recall that Q1 2021 included $53 million related to our acquisition of Rodeo Therapeutics. Excluding the $53 million for Rodeo in 2021, non-GAAP R&D increased 5% year-over-year. Non-GAAP SG&A expenses in the first quarter declined 1% year-over-year. We continue to focus on prioritizing key investments and activities and driving productivity.

請注意，2021年第一季包含與收購Rodeo Therapeutics相關的5,300萬美元支出。若不計入2021年Rodeo的這5,300萬美元支出，非GAAP研發支出較去年同期成長5%。第一季非GAAP銷售、管理及行政費用較去年同期下降1%。我們將繼續專注於優先進行關鍵投資和活動，並提高生產效率。

Non-GAAP other income and expenses were a net $413 million expense in Q1. This line item is driven by interest expense and our share of BeiGene results as a result of our use of the equity method of accounting. We have a strong balance sheet, generate significant cash flow and retain excellent financial flexibility to evaluate strategic business development opportunities.

第一季非GAAP其他收入和支出淨額為4.13億美元。此項目主要由利息支出以及我們因採用權益法核算而應佔的百濟神州業績份額構成。我們擁有穩健的資產負債表，現金流充裕，並維持著極佳的財務彈性，能夠評估策略性業務發展機會。

We continue to execute on our capital allocation priorities. First, investing in the best innovation, internal and external; second, investing in our business through capital expenditures, including for our new environmentally friendly facilities under construction in Ohio and North Carolina; and third, returning capital to shareholders through growing dividends, including $1.94 per share in the quarter, representing a 10% increase from Q4 2021; and fourth, opportunistic share repurchases, including 24.6 million shares of common stock in the first quarter, which included 23.3 million initial shares received and retired under the accelerated stock buyback agreement.

我們繼續執行既定的資本配置優先事項。首先，投資於最佳創新項目，包括內部和外部項目；其次，透過資本支出投資於我們的業務，包括正在俄亥俄州和北卡羅來納州建設的新型環保設施；第三，透過提高股息向股東返還資本，本季度每股股息為1.94美元，較2021年第四季度增長10%；第四

Turning to the outlook for the business for 2022. We're pleased with our growth to date in 2022, and we're tracking to our 2022 plan. Accordingly, we're reaffirming our 2022 guidance with a revenue range of $25.4 billion to $26.5 billion and a non-GAAP EPS range of $17 to $18. This non-GAAP EPS guidance does not include upfront expenses that may occur from certain types of transactions in the future. Similar to our peers, we have updated our non-GAAP policy to no longer exclude such expenses from our non-GAAP results in accordance with guidance recently issued by the SEC.

展望2022年的業務前景，我們對2022年迄今的成長感到滿意，並且正朝著既定的2022年計畫穩步邁進。因此，我們重申2022年業績指引，預計營收為254億美元至265億美元，非GAAP每股收益為17美元至18美元。此非GAAP每股盈餘指引不包括未來某些類型交易可能產生的預付費用。與同業類似，我們已根據美國證券交易委員會（SEC）近期發布的指引，更新了非GAAP政策，不再從非GAAP業績中排除此類費用。

For reference, the only impact as we recast 2021 to incorporate this change is that our non-GAAP operating expenses will now include 2 items that were previously excluded in 2021. First, $1.5 billion recorded and acquired in-process R&D associated with the Five Prime acquisition in Q2 2021. And second, $400 million recorded in research and development related to an upfront payment to license rights to AMG 451 from Kyowa Kirin Co. in Q3 2021.

作為參考，由於我們重新調整了 2021 年的財務報表以納入此變化，唯一的影響是我們的 2021 年非 GAAP 營運費用現在將包括先前在 2021 年排除的兩項內容。第一項是 2021 年第二季與收購 Five Prime 相關的在研研發費用 15 億美元。第二項是 2021 年第三季與向 Kyowa Kirin Co. 支付 AMG 451 許可權預付款相關的研發費用 4 億美元。

Important additional points to consider for the remainder of 2022. Foreign exchange had an adverse impact on our Q1 2022 sales, and based on current rates, it is expected to create headwinds to our reported product sales of approximately $400 million year-over-year and has been included in our guidance. We note that while the results of our hedging program are reported in product sales, our hedging program is designed to partially mitigate the foreign exchange impact on our net income over the full year. In total, our 2022 non-GAAP EPS guidance includes a negative impact from foreign exchange of approximately 2% or approximately $0.35.

以下幾點是2022年剩餘時間需要考慮的重要補充事項。外匯波動對我們2022年第一季的銷售額產生了不利影響，根據目前的匯率，預計將使我們報告的產品銷售額同比減少約4億美元，並已將此影響納入我們的業績指引。我們注意到，雖然我們的避險計畫的成果已計入產品銷售額，但該計畫旨在部分緩解外匯波動對我們全年淨利潤的影響。總而言之，我們2022年非GAAP每股盈餘指引已包含約2%（約0.35美元）的外匯負面影響。

We continue to expect other revenue for 2022 to be in the range of $1.4 billion to $1.7 billion. Q1 included a majority of our full year's projected revenue from our COVID collaboration and recall that these revenues in 2021 were recognized across Q2 to Q4. Our COVID collaboration revenue outlook depends on the state of the pandemic and continued government support. Our expectations for total non-GAAP operating expenses for 2022 are unchanged from the last time we spoke. However, when comparing against our recast 2021 results, total non-GAAP operating expenses will now reflect a low double-digit decrease year-over-year. We continue to expect 2022 operating margin as a percentage of product sales to be roughly 50%. We continue to expect cost of sales as a percent of product sales to be 15.5% to 16.5%.

我們仍預計2022年其他收入將在14億美元至17億美元之間。第一季包含了我們全年預計的大部分新冠疫情合作項目收入，需要注意的是，這些收入在2021年已分攤到第二季至第四季確認。我們對新冠疫情合作計畫收入的預期取決於疫情狀況和政府的持續支持。我們對2022年非GAAP營運總費用的預期與上次溝通時相同。但是，與我們重述後的2021年業績相比，非GAAP營運總費用將比去年同期下降兩位數。我們仍預期2022年營業利潤率（佔產品銷售額的百分比）約為50%。我們仍預期銷售成本（佔產品銷售額的百分比）為15.5%至16.5%。

Our expectations for non-GAAP R&D expenses in 2022 remain unchanged. Based on our recast 2021 results, in response to the SEC guidance mentioned above, which increased non-GAAP R&D expense in 2021 by $400 million, our expected 2022 non-GAAP R&D expense now equates to a decrease of 4% to 6% year-over-year. We continue to expect SG&A spend to be flat year-over-year as a percentage of product sales. And we now expect other income and expenses to be in the range of $1.6 billion to $1.8 billion, reflecting increasing interest rates and our share of BeiGene's results. This is a change from our previous range of $1.4 billion to $1.6 billion.

我們對2022年非GAAP研發費用的預期維持不變。根據我們為回應上述美國證券交易委員會（SEC）的指導意見而重述的2021年業績（該指導意見將2021年非GAAP研發費用增加了4億美元），我們預計2022年非GAAP研發費用將年減4%至6%。我們仍預期銷售、管理及行政費用佔產品銷售額的比例將與上年持平。此外，鑑於利率上升以及我們在百濟神州業績中所佔份額，我們現在預計其他收入和支出將在16億美元至18億美元之間。這與我們先前預測的14億美元至16億美元有所不同。

And for the full year, we anticipate a non-GAAP tax rate range of 13.5% to 14.5%, up from our prior guidance of 13% to 14%.

對於全年，我們預期非GAAP稅率區間為13.5%至14.5%，高於我們先前13%至14%的預期。

You've had an opportunity to read the update to our litigation and dispute with the IRS over the proposed adjustments for the period from 2010 to 2015, included in the press release. We firmly believe that the adjustments proposed by the IRS for that time period and the penalties proposed by the IRS for the 2013 to 2015 period are without merit.

您已有機會閱讀新聞稿中關於我們與美國國稅局就2010年至2015年期間擬議調整方案進行的訴訟和爭議的最新進展。我們堅信，美國國稅局針對該期間提出的調整方案以及針對2013年至2015年期間提出的罰款均毫無根據。

Further, the amount of the adjustments proposed by the IRS for 2010 to 2015 period overstates by billions of dollars the magnitude of the dispute. We filed a petition in the U.S. Tax Court in July 2021 to contest the adjustments previously proposed for the 2010 to 2012 period. And we plan to file another petition in the U.S. Tax Court to contest the adjustments proposed in the notice for the 2013 to 2015 period. The dispute is expected to take several years to resolve.

此外，美國國稅局提出的2010年至2015年期間的調整金額高估了爭議的嚴重程度，高達數十億美元。我們已於2021年7月向美國稅務法院提起訴訟，對先前提出的2010年至2012年期間的調整提出異議。我們計劃再次向美國稅務法院提起訴訟，對通知中提出的2013年至2015年期間的調整提出異議。預計這場爭議將持續數年才能解決。

Amgen believes the IRS assertion of approximately $2 billion in penalties for the 2013 to 2015 period is wholly unwarranted. We've applied a consistent transfer pricing methodology since 2002. We've documented that transfer pricing methodology is required under relevant tax regulations and have extensively discussed that methodology with the IRS across multiple tax audits over multiple tax years. The IRS has never previously proposed transfer pricing penalties.

安進公司認為，美國國稅局對2013年至2015年期間約20億美元的罰款要求完全沒有根據。自2002年以來，我們一直採用一致的轉讓定價方法。我們已記錄在案，相關稅法法規要求採用轉讓定價方法，並在多個納稅年度的多次稅務審計中與美國國稅局就該方法進行了深入討論。美國國稅局此前從未提出過轉讓定價罰款要求。

Amgen also believes, based upon the positions advanced by the IRS, that the IRS adjustments for the 2010 to 2015 period are overstated by approximately $2 billion due to the IRS failure to account for certain income and expenses. Amgen has reported its income and expenses in a consistent manner for many years, and the IRS has appropriately accounted for the company's income and expenses in all prior audits.

根據美國國稅局（IRS）的立場，安進公司也認為，由於IRS未能對某些收入和支出進行核算，其對2010年至2015年期間的調整金額被高估了約20億美元。多年來，安進公司一直以一致的方式報告其收入和支出，而IRS在先前的所有審計中都對該公司的收入和支出進行了適當的核算。

Any additional tax that could be imposed for the 2010 to 2015 period would be reduced by up to approximately $3.1 billion of repatriation tax previously accrued with respect to the company's Puerto Rico earnings. Amgen previously made advanced tax deposits to the IRS totaling $1.1 billion for the 2010 to 2015 period. These deposits would further reduce any additional cash tax that could be imposed.

2010年至2015年期間可能徵收的任何額外稅款，都將因該公司先前就其波多黎各收益累計的約31億美元的匯回稅款而減少。安進公司先前已向美國國稅局預繳了2010年至2015年期間的稅款，總額達11億美元。這些預繳稅款將進一步減少任何可能徵收的額外現金稅。

The IRS is currently auditing the 2016 to 2018 period. We expect the audit to continue for several years, and it is possible that the 2010 to 2015 dispute will be resolved before the conclusion of the 2016 to 2018 audit and administrative appeals process. Any transfer pricing adjustments the IRS may propose for this period will be lessened by the change in tax rates resulting from the 2017 tax reform law, which reduced the difference between the tax rates applicable in the U.S. and Puerto Rico by approximately 2/3 beginning in 2018.

美國國稅局目前正在對2016年至2018年期間進行審計。我們預計審計將持續數年，2010年至2015年的爭議有可能在2016年至2018年審計和行政申訴程序結束前得到解決。由於2017年稅改法案導致稅率變化，美國國稅局可能針對該期間提出的任何轉讓定價調整都將減少。該法案自2018年起將美國和波多黎各適用稅率之間的差異縮小了約三分之二。

We are highly confident in our positions in the litigation and dispute. We are grateful to all of our highly skilled colleagues in Puerto Rico and their important and ongoing contributions to Amgen's mission of serving patients. And now back to the mission of serving every patient every time. Our confidence in the long-term growth of Amgen remains strong given the strength of the business and our outstanding and dedicated team of 24,000 colleagues that deliver every day for patients.

我們對自身在訴訟和爭議中的立場充滿信心。我們衷心感謝波多黎各所有技藝精湛的同事，感謝他們為安進服務患者的使命所做的重要且持續的貢獻。現在，讓我們回到「始終如一地服務每一位患者」的使命上。鑑於公司業務的穩健發展以及我們24,000名傑出且敬業的同事每天為患者提供優質服務，我們對安進的長期增長依然充滿信心。

This concludes the financial update. I'll now turn it over to Murdo.

財務報告到此結束。現在我將把發言權交給默多。

Thanks, Peter. First quarter product sales increased 2% year-over-year. We continue to progress our volume-driven growth strategy, which led to a 9% volume increase globally in Q1. We delivered record quarterly sales for Repatha, EVENITY and BLINCYTO; and double-digit volume growth for several additional products, including Prolia, KYPROLIS and AMGEVITA.

謝謝Peter。第一季產品銷售額較去年同期成長2%。我們持續推動以銷量驅動的成長策略，該策略使第一季全球銷量成長了9%。 Repatha、EVENITY和BLINCYTO的季度銷售額均創歷史新高；此外，包括Prolia、KYPROLIS和AMGEVITA在內的其他幾款產品也實現了兩位數的銷售成長。

In the first 2 months of the year, COVID-19 affected our business in the U.S. and around the world as the Omicron variant led to diminished capacity in the health care sector and reduced working days for our own sales forces. In March and continuing into April, the impact of Omicron in the U.S. receded, which allowed us to engage in increased face-to-face customer interactions. Provider and patient activity have also increased, leading to improvements in demand for our products.

今年前兩個月，由於新冠疫情導致奧密克戎病毒變異株感染，醫療保健行業產能下降，我們銷售團隊的工作日也相應減少，從而對我們在美國及全球的業務造成了影響。 3月及4月，奧密克戎病毒在美國的影響逐漸消退，使我們能夠與客戶進行更多面對面的交流。同時，醫療機構和病患的就診量也有所增加，進而帶動了我們產品需求的成長。

Now let me review some product details, beginning with our general medicine portfolio, which includes Prolia, EVENITY, Repatha and Aimovig. Overall revenue for our general medicine portfolio grew 19% year-over-year with 23% volume growth. In bone health, Prolia sales grew 12% year-over-year. Volumes grew 10%, fueled by an increase in both new and repeat patients. EVENITY, which complements Prolia in our bone portfolio, had record sales of $170 million for the quarter, driven by strong volume growth across our markets.

現在讓我來回顧一下產品詳情，首先是我們的普通藥物產品組合，其中包括普羅利亞（Prolia）、伊凡尼（EVENITY）、瑞百安（Repatha）和艾莫維（Aimovig）。我們一般藥品產品組合的整體營收年增19%，銷售量成長23%。在骨骼健康領域，普羅利亞的銷售額年增12%，銷量成長10%，這主要得益於新患者和復診患者的增加。伊凡尼是普羅利亞在骨骼健康產品組合中的補充，本季銷售額創下1.7億美元的紀錄，主要得益於我們在各市場銷售的強勁成長。

Moving to Repatha, the global leader in the PCSK9 class. Repatha sales increased 15% year-over-year, driven by 49% volume growth. And in the U.S., we saw 41% volume growth. Net selling prices declined as we offered higher rebates to support broad Medicare Part D and commercial patient access. Outside the U.S., sales grew 12% with strong volume growth coming from the inclusion of Repatha on China's National Reimbursement Drug List beginning January 1. We remain focused on increasing Repatha market penetration globally to address the significant unmet medical need in treating high-risk cardiovascular patients.

接下來是PCSK9抑制劑類藥物Repatha，該類藥物在全球市場處於領先地位。 Repatha的銷售額較去年同期成長15%，主要得益於銷售成長49%。在美國，銷量成長41%。由於我們提高了回扣，以支持更多聯邦醫療保險D部分（Medicare Part D）和商業保險患者獲得治療，因此淨售價有所下降。在美國以外地區，銷售額成長12%，銷售強勁成長主要得益於Repatha自1月1日起納入中國國家健保藥品目錄。我們將持續致力於提高Repatha在全球的市場滲透率，以滿足高風險心血管疾病患者治療領域尚未充分滿足的醫療需求。

Moving to our inflammation portfolio. Otezla delivered 7% year-over-year volume growth in the first quarter. In the U.S., we saw a strengthening of the market with Otezla remaining the market leader, achieving a 30% share of patients who are new to systemic agents for psoriasis. Otezla's recently expanded label has been well received by payers, providers and patients. We're seeing early signs of physicians using more systemic treatments for mild psoriasis patients, and the majority of dermatologists anticipate increasing the use of Otezla for mild psoriasis.

接下來談談我們的發炎產品組合。 Otezla在第一季實現了7%的同比增長。在美國，市場表現強勁，Otezla繼續保持市場領先地位，在首次使用系統性乾癬藥物的患者中佔據了30%的市場份額。 Otezla近期擴大的適應症受到了支付方、醫療服務提供者和患者的歡迎。我們觀察到，醫生開始更多地使用系統性療法治療輕度乾癬患者，大多數皮膚科醫生預計Otezla在輕度乾癬治療中的應用將會增加。

Globally, Otezla sales decreased 5% year-over-year due to net price declines and lower inventory levels in the U.S. across wholesale and specialty pharmaceutical channels. Otezla net price declines in the U.S. were driven primarily by enhancements to our co-pay and bridge programs to support new patients starting treatment. Looking forward, we expect lower year-on-year price erosion for the remaining quarters of 2022. We also expect continued volume growth driven by broader adoption of Otezla, given our unique broad indication regardless of the severity of psoriasis.

全球範圍內，由於淨價下降以及美國批發和專科藥品通路庫存水準降低，Otezla 的銷售額年減了 5%。 Otezla 在美國的淨價下降主要得益於我們加強了共同支付和過渡性治療方案，以支持新患者開始治療。展望未來，我們預計 2022 年剩餘季度的年比價格跌幅將有所縮小。鑑於 Otezla 獨特的廣泛適應症（無論銀屑病嚴重程度如何），我們預計隨著 Otezla 的普及，銷售將持續增長。

ENBREL sales decreased 7% year-over-year for the first quarter, driven by declines in net selling price and inventory levels. Year-over-year, volume remained flat in the first quarter, supported by ENBREL's long track record of efficacy and safety.

受淨售價和庫存水準下降的影響，恩利（ENBREL）第一季銷售額年減7%。但由於恩利長期以來療效和安全性良好，其銷量與去年同期持平。

Our launch of TEZSPIRE is off to a strong start, with $7 million in sales in the first quarter. Initial feedback from payers, providers and patients is very positive. Physician's unaided awareness increased to greater than 65% since launch, supported by our disease state education programs. On the access front, TEZSPIRE is a medical benefit product for which we expect permanent reimbursement coding as of July 1 of this year. Both allergists and pulmonologists acknowledge TEZSPIRE's unique differentiated properties and its broad potential to treat the 2.5 million patients worldwide with severe asthma who are uncontrolled or biologic eligible without any phenotypic and biomarker limitations.

TEZSPIRE上市開始開始就取得了強勁的開局，第一季銷售額達700萬美元。來自支付方、醫療服務提供方和患者的初步回饋都非常積極。自上市以來，在疾病狀態教育計畫的支持下，醫師對TEZSPIRE的認知度已超過65%。在市場准入方面，TEZSPIRE是一款醫療福利產品，我們預計自今年7月1日起將獲得永久性的報銷編碼。過敏科醫師和肺科醫師均認可TEZSPIRE獨特的差異化特性及其治療全球250萬重度氣喘患者的巨大潛力，這些患者病情控制不佳或符合生物製劑治療條件，且不受任何表型和生物標記限制。

Moving to the hematology and oncology business. Our 6 innovative products grew 17% year-over-year with 11% volume growth. We saw strong volume growth from KYPROLIS, Nplate and BLINCYTO, which we expect to continue throughout this year. XGEVA sales grew 7% year-over-year, while volumes declined 2%.

接下來是血液腫瘤業務。我們的6款創新產品年增17%，銷售量成長11%。 KYPROLIS、Nplate和BLINCYTO的銷售成長強勁，我們預計這一成長動能將持續到今年年底。 XGEVA的銷售額較去年同期成長7%，但銷量下降了2%。

Our launch of LUMAKRAS is progressing well with revenues of $62 million in the first quarter, representing 38% quarter-over-quarter growth. In the U.S., LUMAKRAS has been prescribed to approximately 2,500 patients by over 1,500 physicians in both academic and community settings since launch. While approximately 80% of patients in the U.S. are tested for their KRAS G12C status, the test result is not always available and/or reviewed when the patient progresses beyond first-line therapy.

LUMAKRAS的上市進展順利，第一季營收達6,200萬美元，較上季成長38%。自上市以來，LUMAKRAS已在美國被1500多位醫生用於治療約2500名患者，這些醫生來自學術機構和社區醫療機構。雖然美國約80%的患者接受了KRAS G12C基因狀態檢測，但當患者接受第一線治療後病情進展時，檢測結果並非總能及時獲得或得到複查。

The opportunity to improve care is to ensure the KRAS G12C status is available in the patient chart, or electronic medical record and reviewed by the oncologist to ensure that LUMAKRAS is discussed as an option for the patient. LUMAKRAS has strong payer coverage in the U.S., with 93% of patients having formulary access. Outside the U.S., sotorasib has now been approved in nearly 40 countries around the world with recent reimbursement approvals in the United Kingdom and Japan.

改善治療的契機在於確保病患病歷或電子病歷中包含KRAS G12C狀態訊息，並由腫瘤科醫師審核，以便將LUMAKRAS作為病患的治療選擇之一進行討論。 LUMAKRAS在美國擁有強大的健保覆蓋範圍，93%的患者可獲得健保報銷。在美國以外，索托拉西布已在全球近40個國家獲得批准，並於近期在英國和日本獲得醫療保險報銷。

Sales of our oncology biosimilars declined 25% year-over-year. While our biosimilars, MVASI and KANJINTI, both hold leading shares, we expect continued net selling price deterioration and volume declines, driven by increased competition and ASP erosion. Over time, we expect long-term growth in our biosimilars business to be driven by the addition of new molecules and additional launches beginning with AMGEVITA in the United States in January of 2023.

我們的腫瘤生物相似藥銷售額較去年同期下降了25%。儘管我們的生物相似藥MVASI和KANJINTI均佔據領先市場份額，但我們預計，受競爭加劇和平均售價下降的影響，淨售價將持續走低，銷量也將持續下滑。展望未來，我們預期生物相似藥業務的長期成長將主要得益於新分子的推出和更多產品的上市，其中AMGEVITA將於2023年1月在美國上市。

Overall, we're executing well against our growth strategy with strong volume trends across our portfolio. With that, I'll turn it to Dave.

整體而言，我們的成長策略執行良好，旗下所有產品組合的銷售量均呈現強勁成長動能。接下來，我將把發言權交給戴夫。

Thanks, Murdo. Good afternoon, everyone. First quarter was one of continued execution in R&D, where we focused on progressing our robust innovative clinical pipeline comprised of many potential first-in-class opportunities. Beginning with inflammation, we initiated 2 additional studies with TEZSPIRE in severe asthma: the WAYFINDER Phase IIIb study, designed to demonstrate a reduction in oral corticosteroid use in adult participants on long-term oral corticosteroid therapy; and the PASSAGE Phase IV real-world effectiveness study, designed to evaluate TEZSPIRE in adult and adolescent participants, including underrepresented populations such as Black Americans, smokers and patients with asthma-COPD overlap.

謝謝，Murdo。大家下午好。第一季我們持續推動研發工作，重點是推動我們強大的創新臨床管線，其中包含許多潛在的同類首創藥物。首先是發炎領域，我們啟動了兩項針對重度氣喘的TEZSPIRE新研究：WAYFINDER IIIb期研究，旨在證明TEZSPIRE能夠減少長期口服糖皮質激素治療的成年患者的口服糖皮質激素用量；以及PASSAGE IV期真實世界療效研究，旨在評估TEZSPIRE在成人和青少年患者中的療效，包括非裔美國人、肺部疾病患者以及慢性疾病患者重疊的影響

Phase III planning continues for rocatinlimab, formerly AMG 451, an anti-OX40 monoclonal antibody being investigated in patients with heterogeneous moderate to severe atopic dermatitis. Rocatinlimab binds activated pathogenic T cells expressing OX40. Through its unique mechanism of action, rocatinlimab inhibits and prevents the expansion of activated pathogenic T cells and reduces their number. Thus, rocatinlimab has the potential to lead to profound disease control. In addition, this provides a rationale for longer dosing intervals, with the prospect of achieving disease modification. ROCKET, the comprehensive rocatinlimab Phase III program, remains on track to initiate in mid-2022.

rocatinlimab（原名AMG 451）是一種抗OX40單株抗體，目前正在研究其對異質性中重度異位性皮膚炎患者的療效。此抗體可與表達OX40的活化致病性T細胞結合。 rocatinlimab透過其獨特的作用機制，抑制並阻止活化致病性T細胞的擴增，從而減少其數量。因此，rocatinlimab可望顯著控制病情。此外，這也為延長給藥間隔提供了理論基礎，有望實現疾病改善。 rocatinlimab的綜合性III期臨床試驗計畫ROCKET仍按計畫於2022年中期啟動。

In our biosimilar portfolio, last week, we announced preliminary results from a Phase III study evaluating the efficacy and safety of ABP 654 compared to STELARA, ustekinumab, in adult patients with moderate to severe plaque psoriasis. The study met the primary efficacy endpoint, demonstrating no clinically meaningful differences between ABP 654 and STELARA.

上週，我們公佈了生物相似藥產品組合中一項評估ABP 654與STELARA（烏司奴單抗）在治療中重度斑塊狀銀屑病成人患者中的療效和安全性的III期研究的初步結果。該研究達到了主要療效終點，顯示ABP 654與STELARA之間無臨床意義上的差異。

Now turning to oncology. Earlier this month, we presented data at AACR on outcomes from a 2-year analysis of the LUMAKRAS CodeBreaK 100 trial, which demonstrated the long-term clinical benefit, including overall survival of patients with KRAS G12C mutated advanced non-small cell lung cancer treated with LUMAKRAS. These data showed that roughly 1/3 of patients were still alive at 2 years and that the prolonged tumor response was observed with a 41% objective response rate by central review.

現在我們來談談腫瘤學。本月初，我們在美國癌症研究協會（AACR）年會上發表了LUMAKRAS CodeBreaK 100試驗兩年的分析結果。此分析證實了LUMAKRAS治療KRAS G12C突變晚期非小細胞肺癌患者的長期臨床獲益，包括總存活期。數據顯示，約三分之一的患者在兩年後仍存活，且中心審查顯示，腫瘤反應持續時間延長，客觀緩解率達41%。

While this was a single-arm trial without a control arm, the efficacy data compare favorably with anticipated outcomes in this patient population based on historical data. There were no new safety signals reported over the course of this 2-year follow-up analysis. We have submitted data from the LUMAKRAS PD-1 combination and SHIP2 combination cohorts to a medical congress taking place in the late summer, while top line results from the LUMAKRAS confirmatory Phase III study versus docetaxel and the dose comparison study are on track for Q3 and Q4, respectively.

儘管這是一項沒有對照組的單臂試驗，但其療效數據與基於歷史數據對該患者群體預期結果相比，表現良好。在為期兩年的追蹤分析中，未報告新的安全性訊號。我們已將LUMAKRAS PD-1聯合療法和SHIP2聯合療法隊列的數據提交至將於夏末舉行的醫學大會，而LUMAKRAS與多西他賽的III期確證性研究以及劑量比較研究的主要結果預計將分別於第三季度和第四季度公佈。

Also in the lung cancer setting, we have submitted updated Phase I data of tarlatamab, our DLL3-targeting half-life extended BiTE molecule being used in patients with relapsed/refractory small cell lung cancer to a medical congress taking place in the late summer. And we plan to initiate DeLLphi-303, a Phase Ib study testing tarlatamab in combination with standard of care in first-line small cell lung cancer this quarter.

在肺癌領域，我們已向將於夏末舉行的醫學大會提交了tarlatamab的最新I期臨床試驗數據。 tarlatamab是一種針對DLL3的長效BiTE分子，用於治療復發/難治性小細胞肺癌患者。此外，我們計劃在本季度啟動DeLLphi-303研究，這是一項Ib期臨床試驗，旨在評估tarlatamab聯合一線標準治療方案治療小細胞肺癌的療效。

Finally, in squamous non-small cell lung cancer, we are enrolling patients in a Phase Ib study of bemarituzumab, a monoclonal antibody directed against FGFR2b.

最後，在鱗狀非小細胞肺癌中，我們正在招募患者參與貝馬裡單抗（一種針對 FGFR2b 的單株抗體）的 Ib 期研究。

Turning to gastrointestinal cancers. We presented data at the ASCO plenary series in February, where LUMAKRAS demonstrated a centrally confirmed objective response rate of 21% and disease control rate of 84% across 38 heavily pretreated advanced pancreatic cancer patients. We continue to explore the benefit of LUMAKRAS as a monotherapy and when combined with other agents in this setting.

接下來我們來談談胃腸道腫瘤。我們在2月的ASCO全體會議上公佈了LUMAKRAS的數據，結果顯示，在38例既往接受過大量治療的晚期胰腺癌患者中，LUMAKRAS的客觀緩解率（ORR）經中心實驗室驗證為21%，疾病控制率為84%。我們將繼續探索LUMAKRAS作為單藥療法以及與其他藥物聯合治療在此類患者中的療效。

In third-line colorectal cancer, Phase III study of LUMAKRAS in combination with Vectibix is enrolling patients. In gastric cancer, a Phase Ib study of bemarituzumab plus oral chemotherapy regimens in tumors with FGFR2b over expression has been initiated.

在大腸直腸癌三線治療中，LUMAKRAS合併Vectibix的III期臨床研究正在招募病患。在胃癌方面，一項針對FGFR2b過度表現腫瘤的bemarituzumab合併口服化療方案的Ib期臨床研究已啟動。

In general medicine, we were pleased to announce the results from 2 Repatha open-label extension trials, the FOURIER-OLE study, designed to assess the long-term safety and tolerability of Repatha in more than 6,600 high-risk adults with clinically evident atherosclerotic cardiovascular disease on stable effective statin therapy.

在一般醫學領域，我們很高興地宣布了兩項 Repatha 開放標籤擴展試驗的結果，即 FOURIER-OLE 研究，該研究旨在評估 Repatha 在 6600 多名患有臨床上明顯的動脈粥樣硬化性心血管疾病且正在接受穩定有效他汀類藥物治療的高危險成年人中的長期安全性和耐受性。

In the OLE studies, patients receive Repatha for approximately 5 years, with some patients receiving Repatha for up to 8.5 years in aggregate across the FOURIER and OLE studies. The combined results from these studies reinforce the long-term safety and tolerability of Repatha in lowering LDL cholesterol. We are extremely encouraged by the sustained benefit of this medicine in patients with cardiovascular disease who still struggle to get their LDL-cholesterol level below the recommended targets.

在開放標籤擴展研究（OLE）中，患者接受瑞百安治療約5年，部分患者在FOURIER研究和OLE研究中累計接受瑞百安治療長達8.5年。這些研究的綜合結果進一步證實了瑞百安在降低低密度脂蛋白膽固醇方面的長期安全性和耐受性。我們非常欣慰地看到，對於那些仍難以將低密度脂蛋白膽固醇水平降至建議目標以下的心血管疾病患者而言，該藥物的持續療效令人鼓舞。

These extended results for patients on Repatha are consistent with what the health care community has learned over the past 7 decades about the benefits of lowering cholesterol. That is robust and sustained LDL cholesterol reduction affects the spectrum of important cardiovascular outcomes. We look forward to sharing these data at a medical congress later this year.

瑞百安（Repatha）患者的這些長期療效與過去七十年來醫療界對降低膽固醇益處的認識相符。也就是說，持續有效地降低低密度脂蛋白膽固醇（LDL-C）水平能夠改善一系列重要的心血管疾病結果。我們期待在今年稍後的醫學大會上分享這些數據。

In conclusion, we continue to execute crisply across our innovative and biosimilar portfolios and look forward to sharing new data from a number of our programs throughout the rest of the year. With that, I'll turn it back to Bob for Q&A.

總之，我們繼續在創新藥和生物相似藥產品組合方面保持高效執行，並期待在今年餘下的時間裡分享我們多個專案的新數據。接下來，我會把問答環節交給鮑伯。

Okay. Thank you, Dave. RJ, could you remind our callers of the process for submitting a question? We're happy to answer questions now.

好的。謝謝你，戴夫。 RJ，你能提醒一下來電者提問的流程嗎？我們現在很樂意回答問題。

(Operator Instructions) Your first question comes from the line of Michael Yee from Jefferies.

（操作說明）您的第一個問題來自 Jefferies 的 Michael Yee 的線路。

Can you hear me okay?

你聽得清楚我說話嗎？

Yes, Mike, go ahead.

好的，麥克，請繼續。

Very good. Question for Dave. Obviously, the KRAS field is quite competitive, and you have a very important Phase III LUMAKRAS confirmatory study reading out. I just wanted to know your confidence around the expectations for a positive result there against docetaxel, how fast you could file that and whether that changes the paradigm for accelerated approvals for competitors around you. So maybe just comment on that study and the ramifications.

很好。問Dave一個問題。顯然，KRAS標靶治療領域競爭非常激烈，而你們的LUMAKRAS III期確證性研究結果即將公佈，這非常重要。我想了解您對該研究結果的信心，以及您預計多久能提交上市申請，還有，這是否會改變你們競爭對手加速審批的格局。所以，請您談談這項研究及其影響。

Yes. If we replicate what we've observed so far with LUMAKRAS, I think, Mike, we would be quite confident in the likelihood that the Phase III trial against docetaxel, which, of course, has been around for decades, will be positive. We would, of course, discuss with the FDA and other regulatory bodies how to file these data and move forward with full approvals. In terms of effects on the competitive landscape, I'll leave that to others to comment on. But we're very confident in LUMAKRAS at this point. We're approved in roughly 40 countries around the world. The program is moving forward very briskly, and that's our focus right now.

是的。如果我們能複製目前在LUMAKRAS上觀察到的結果，我認為，麥克，我們會非常有信心，LUMAKRAS與多西他賽（當然，多西他賽已經上市幾十年了）的III期臨床試驗結果會是積極的。當然，我們會與FDA和其他監管機構討論如何提交這些數據，並推動全面審批流程。至於對競爭格局的影響，我留給其他人來評論。但目前我們對LUMAKRAS非常有信心。它已在全球約40個國家獲得批准。該項目正在快速推進，這也是我們目前的重點。

Your next question comes from the line of Jay Olson from Oppenheimer.

你的下一個問題來自奧本海默公司的傑伊·奧爾森。

As you continue to generate important new clinical data for Repatha, you have data coming for Olpasiran, AMG 133. I saw you recently published data for AMG 986 for heart failure. It seems like you're building an increasingly strong cardiovascular portfolio. Can you just talk about your strategy in cardiovascular disease? And what are the large opportunities there? And are there any gaps in your cardiovascular portfolio where you may want to pursue business development opportunities?

隨著您持續獲得Repatha的重要臨床數據，Olpasiran和AMG 133的數據也即將發布。我看到您最近發布了AMG 986治療心臟衰竭的數據。看來您正在建立一個日益強大的心血管產品組合。您能否談談您在心血管疾病領域的策略？該領域有哪些巨大的機會？您的心血管產品組合中是否存在一些空白領域，您希望在這些領域尋求業務拓展機會？

Why don't I take the last piece of that? And Dave, why don't you respond to the first? I'll start. I think Murdo wanted to comment as well and could jump in. Thanks, Jay. I think you raised an incredibly important question. As you're all aware, cardiovascular disease is 1 of our 3 principal areas of therapeutic areas for research. It remains an area of focus for us going forward. It remains the #1 public health burden in terms of morbidity and mortality across the globe. And that, in part, is what spurs our commitment here with Repatha. Murdo will comment in a minute, but we believe there is tremendous opportunity to serve patients on a hypothesis that's probably the best proved in medicine in terms of LDL cholesterol.

我來回答最後一個問題吧？戴夫，你先回答第一個問題？我先來。我想默多也想發表意見，他可以插嘴。謝謝，傑伊。我認為你提出了一個極為重要的問題。大家都知道，心血管疾病是我們三大主要治療研究領域之一，也是我們未來研究的重點領域。它仍然是全球發病率和死亡率最高的公共衛生負擔。這在某種程度上促使我們致力於研發瑞百安（Repatha）。默多稍後會發表評論，但我們相信，基於目前醫學界在降低低密度脂蛋白膽固醇方面可能最充分的假設，我們有機會為患者帶來巨大的福祉。

You mentioned the Lp(a) program, Olpasiran, or AMG 890. Just to remind everyone, Lp(a) is probably the single most important driver outside of LDL cholesterol in terms of the pathogenesis of atherosclerotic cardiovascular disease. As I noted, we're looking forward to, over the next couple of months, Phase IIb data in those programs. And our goal would be to transition to Phase III as quickly as possible if those data replicate what we saw in Phase I. In addition, we have a very active preclinical research portfolio, I think, indicating our ongoing strategic commitment to this area.

您提到了Lp(a)專案、Olpasiran或AMG 890。在此提醒大家，Lp(a)可能是除低密度脂蛋白膽固醇外，在動脈粥狀硬化性心血管疾病發病機轉中最重要的驅動因素。正如我之前提到的，我們期待在未來幾個月內獲得這些專案的IIb期資料。如果IIb期資料與I期資料一致，我們的目標是盡快進入III期。此外，我們擁有非常活躍的臨床前研究計畫組合，我認為這顯示了我們對該領域的持續策略投入。

Murdo, maybe I'll turn it to you next and then Bob can talk about the business development.

默多，也許接下來該輪到你了，然後鮑伯可以談談業務拓展方面的事情。

Thanks, Dave. Underpinning, obviously, the huge unmet medical need of cardiovascular disease is our ability to reach that global population of patients, and we've built the medical and commercial capabilities and global footprint to support that business. We reported 49% volume growth on Repatha, 15% sales growth year-on-year. So we clearly have momentum now, and we continue to feel that there's more for us to do for these patients.

謝謝戴夫。顯然，心血管疾病領域巨大的未滿足醫療需求取決於我們能否觸及全球患者群體，而我們已經建立了相應的醫療和商業能力以及全球佈局來支持這項業務。我們報告稱，Repatha 的銷量成長了 49%，銷售額較去年同期成長了 15%。因此，我們目前的發展勢頭強勁，而且我們仍然認為，我們還能為這些患者做更多的事情。

We're also very clear that we are focused on improving the affordability of our medicines for these patients. And I think that that's another area we've made great progress. So adding to that portfolio with our own internal pipeline is a welcome thing. And I think Dave's team is working very hard, not only on the pipeline assets, but also to improve the profile of Repatha with the VESALIUS trial, which is ongoing. And of course, the recently announced long-term follow-up trials that were continued. So the profile of Amgen in cardiovascular disease is strong. And I'll turn it over to Bob on the business development.

我們也非常明確地表示，我們致力於提高這些患者用藥的可負擔性。我認為這是我們取得巨大進展的另一個領域。因此，透過我們自身的內部研發管線來豐富產品組合是一件令人欣喜的事。我認為戴夫的團隊正在非常努力地工作，不僅在研發管線資產方面，而且還在透過正在進行的VESALIUS試驗來提升Repatha的知名度。當然，還有最近宣布的、仍在進行的長期追蹤試驗。因此，安進在心血管疾病領域的實力雄厚。接下來，我將把業務拓展方面的發言交給鮑伯。

Yes. And there, it's very simple, Jay. We've challenged our business development and research teams to find attractive innovation externally that we can add to our portfolio. So we're looking for things that we can add value to every day in cardiovascular disease as well as in inflammatory diseases and in cancer.

是的。很簡單，傑伊。我們已經要求業務拓展和研發團隊尋找外部有吸引力的創新成果，並將其添加到我們的產品組合中。因此，我們正在尋找那些能夠每天為心血管疾病、發炎性疾病和癌症領域帶來價值的創新。

Your next question comes from the line of Geoff Meacham from Bank of America.

你的下一個問題來自美國銀行的傑夫‧米查姆。

Peter, a lot more commentary on the tax dispute with the IRS on this earnings call compared to when you first talked about it last year, I think probably a higher number of the investors expected. So the question is, has there been a recent discussion with the agency or the service that prompted broader language today? And I know it's going to take years to fully resolve, but would you expect your tax reserves to change over the course of that discussion? Or is that just something that's going to be a stagnant number? And then when you fully resolve it, then you'll appropriately make that change?

彼得，這次財報電話會議上你對與美國國稅局的稅務糾紛的討論比去年你首次談到時要多得多，我想這可能超出了許多投資者的預期。所以問題是，最近是否與國稅局進行了討論，才導致你今天措辭如此詳盡？我知道徹底解決這個問題需要數年時間，但你預計在討論過程中，你的稅務儲備金會改變嗎？還是說它會保持不變？等到問題徹底解決後，你才會做出相對應的調整？

Yes. Geoff, thank you for the question. Look, we wouldn't -- we're in litigation, so we wouldn't comment on discussions with the IRS first. And then secondly, on reserves, as you can understand, we don't comment on where we're at in terms of the size of the reserves other than we would just simply say that we're very confident in our position and the level of reserves that we've established. And as we said, this is about Puerto Rico and the allocation of profits between the United States and the U.S. territory of Puerto Rico, where we perform a majority of our global manufacturing. Puerto Rico is home to our flagship manufacturing complex, 30-year presence, 2,400 -- 2,400 highly skilled employees, over $4 billion in capital investments. And as we said, we believe that the IRS positions are without merit. We're going to vigorously contest those adjustments proposed for 2010 through 2015.

是的，傑夫，謝謝你的提問。首先，我們正在進行訴訟，所以我們不會對與美國國稅局的討論發表評論。其次，關於儲備金，正如你所理解的，我們不會對儲備金的具體規模發表評論，我們只能說我們對自身的立場和已建立的儲備金水平非常有信心。正如我們所說，這件事關乎波多黎各以及美國與波多黎各（美國領土）之間的利潤分配，我們在波多黎各開展了大部分全球製造業務。波多黎各是我們旗艦製造基地的所在地，該基地已營運30年，擁有2,400名高技能員工，資本投資超過40億美元。正如我們所說，我們認為美國國稅局的立場毫無根據。我們將對2010年至2015年期間提出的調整方案提出強而有力的異議。

Your next question comes from the line of Salveen Richter from Goldman Sachs.

你的下一個問題來自高盛的薩爾文·里希特。

On LUMAKRAS, what steps can you take to ensure that G12C status is recognized by physicians to drive prescriptions here? And could you also frame the outlook for the combo study with KEYTRUDA that's reading out in late summer?

關於LUMAKRAS，您可以採取哪些措施來確保醫師認可G12C狀態，從而促進處方用藥？您能否也談談與KEYTRUDA聯合用藥研究的前景，研究將於夏末公佈結果？

Thanks, Salveen. Maybe I'll start and then turn it over to Dave on the data question. We're obviously working extremely closely with all of the oncology providers to improve their own internal systems, whereby they have that KRAS G12C status with literally fingertip ready for making treatment choices for their patients. What we are seeing is a little bit of a COVID hangover effect. Many of these large oncology networks in the U.S. are short staffed and constrained in the resources that they can deploy against things like EMR enhancements, against things like better workflows for diagnostics and biomarkers, particularly new biomarkers.

謝謝，Salveen。或許我可以先說說，然後把數據方面的問題交給Dave。我們顯然正在與所有腫瘤科醫療機構密切合作，以改善他們的內部系統，使他們能夠迅速掌握KRAS G12C狀態，從而為患者制定治療方案。我們現在看到的是一些新冠疫情的後遺症。美國許多大型腫瘤醫療網絡都面臨人手短缺和資源不足的問題，難以投入電子病歷系統改進、優化診斷和生物標記（尤其是新型生物標記）的工作流程。

So we are working literally account by account across the country. We've made huge improvements. And we've seen some very large community oncology networks, which is where 80% of the patient base is treated. They're treated in the community centers. I think in the academic institutions, the testing is very strong, robust. The care is clear, and the test results are available for patients who progress. So it's really in the U.S. community setting where we're working.

所以我們正在全國各地逐一診所地進行工作。我們已經取得了巨大的進步。我們看到了一些非常龐大的社區腫瘤網絡，80%的患者都在那裡接受治療。他們在社區中心接受治療。我認為在學術機構，檢測非常強大、可靠。治療方案清晰明確，病情進展的患者也能及時獲得檢測結果。所以，我們真正的工作重點是美國的社區醫療機構。

As we look ex U.S., we see a different pattern by country. So countries that have advanced biomarker technology and very clear systems like Germany and France, we expect good uptake there and we're already seeing early indicators of that. France, as you may recall, has an early access program called an ATU program where we can actually charge for the product and that's being used already fairly broadly. And in Germany, we're just launching and a few weeks old, as we are in Japan. So I think it's a network by network project that we're working intensely with our medical colleagues, with our commercial teams to make sure that no patient slips through. Dave?

當我們把目光轉向美國以外的國家時，會發現各國的情況有所不同。像德國和法國這樣擁有先進生物標記技術和完善體系的國家，我們預計這些國家的市場接受度會很高，而且我們已經看到了一些早期跡象。您可能還記得，法國有一個名為「ATU」的早期准入項目，我們可以在這個項目中收取產品費用，而且該項目目前已經得到了相當廣泛的應用。在德國，我們的產品剛上市幾週，在日本也是如此。所以我認為這是一個需要逐個網路推進的項目，我們正在與醫療同事和商業團隊緊密合作，確保沒有患者錯過治療機會。戴夫？

And Salveen, thanks for the question. In terms of data availability, as we noted, we've submitted the data for one of the summer oncology conferences. We are looking at both combination and sequential approaches with PD-1 inhibitors. I'd also point out that one of the things we're beginning to examine is the whole population of patients with non-small cell lung cancer. You can divide them roughly into 1/3 are PD-L1 negative tumors; 1/3 have low to intermediate PD-L1 expression; and 1/3 have high PD-L1 expression. In the PD-L1 negative population, for instance, the effect of checkpoint inhibitors is quite modest, and that's an area where we are looking at combinations of LUMAKRAS with straight chemotherapy. So one thing to keep in mind as this field evolves is that depending on PD-L1 expression, the approach clinically may vary as well. And we are crafting our development program accordingly.

Salveen，謝謝你的提問。關於數據可用性，正如我們之前提到的，我們已經提交了數據，準備在夏季腫瘤學會議上展示。我們正在研究PD-1抑制劑的合併治療和序貫治療方案。我還想指出，我們正在著手研究非小細胞肺癌患者族群。大致可分為三類：1/3為PD-L1陰性腫瘤；1/3為PD-L1低表達至中等表達；1/3為PD-L1高表達。例如，在PD-L1陰性患者族群中，免疫檢查點抑制劑的療效相當有限，因此我們正在研究LUMAKRAS合併單純化療的方案。隨著該領域的發展，需要注意的一點是，臨床治療方案可能會因PD-L1表達量的不同而有所差異。我們也正在據此調整我們的研發計畫。

Your next question comes from the line of Matthew Harrison from Morgan Stanley.

你的下一個問題來自摩根士丹利的馬修·哈里森。

Great. I was hoping a question for Murdo. Murdo, can you just maybe comment -- I know you commented at a business review around your thoughts around contracting and specifically biosimilar contracting as we think about both the HUMIRA launch and some of the other products. Any updated thoughts in terms of how that's going or your expectations on specifically HUMIRA for 2023 versus 2024?

太好了。我正想問默多一個問題。默多，您能否就此發表一下看法？我知道您在一次商業回顧會議上談到了您對合約簽訂，特別是生物相似藥合約簽訂的看法，因為我們都在考慮修美樂（HUMIRA）的上市以及其他一些產品。關於這方面的進展，您有什麼最新的想法嗎？或者您對修美樂在2023年和2024年的預期有何不同？

Thanks, Matthew, for the question. No, I don't really have a lot of new information to update you on. We continue to feel like we're extremely well positioned for the opportunity to be among the first, if not the first, and potentially only biosimilar for a period of time in the market in 2023 as of January 31.

謝謝Matthew的提問。不，我沒有什麼新的資訊可以更新。我們仍然認為，截至2023年1月31日，我們已做好充分準備，預計將成為市場上首批（如果不是第一家的話）甚至可能在一段時間內唯一一家提供生物類似藥的公司。

We like our profile competitively given that we -- as you'll recall, we use the existing inflammation commercial organization that currently commercialize Enbrel and Otezla that have relationships intact with rheumatologists and dermatologists. We actually have a GI footprint as well supporting us solo. So we feel that we've got the customer relationships. We definitely have the payer relationships. We have obviously 40 years of biologics manufacturing and supplying every patient every time to provide the confidence for pharmacy benefit managers to make the decision to make our product available as early as possible.

鑑於我們擁有現有的發炎治療商業機構（如您所知，該機構目前負責恩利和歐特茲拉的商業化），並且與風濕病學家和皮膚科醫生保持著良好的合作關係，我們對自身的競爭優勢感到滿意。此外，我們本身也擁有胃腸道方面的業務支援。因此，我們認為我們擁有穩固的客戶關係，也與支付方建立了良好的合作關係。我們擁有40年的生物製劑生產和供應經驗，始終致力於為每位患者提供所需的藥物，足以讓藥品福利管理機構（PBM）放心，並儘早決定將我們的產品納入醫保範圍。

So we're excited about the opportunity. And then, of course, after the launch of AMGEVITA in the U.S., we have several other launches, STELARA, EYLEA, Soliris and then additional launches thereafter. So 6 new biosimilars coming into the market. So this is an area where we're very focused. We've invested in this area. It's important to us for our long-term growth, and we have the capabilities in the market to ensure success.

所以我們對這個機會感到非常興奮。當然，在AMGEVITA於美國上市後，我們還有幾款產品即將上市，包括STELARA、EYLEA和Soliris，之後還會有更多產品陸續上市。也就是說，將有6款新的生物相似藥進入市場。這是我們非常重視的領域，我們已經在這個領域投入了大量資金。這對我們的長期發展至關重要，而且我們擁有在市場上取得成功的能力。

Your next question comes from the line of Yaron Werber from Cowen & Company.

你的下一個問題來自 Cowen & Company 的 Yaron Werber。

Great. I guess, Peter, maybe for you and for the rest of the team. I guess, Peter, for you, first, the tax rate is increasing incrementally this year. Is that relating to the ongoing litigation with the IRS? Or is that for different reasons?

太好了。彼得，我想，或許對你和團隊其他成員都是如此。首先，彼得，對你而言，今年的稅率是逐步提高的。這和正在進行的與國稅局的訴訟有關嗎？還是另有其他原因？

And then maybe, Murdo, for you. In the U.S., LUMAKRAS is growing, but it's growing probably a bit slower than we expected. Are you expecting ex U.S. to be bigger or similar in size to the U.S.?

或許，默多，對你來說也是如此。在美國，LUMAKRAS 正在發展，但成長速度可能比我們預期的要慢一些。你認為美國以外的市場規模會比美國大，還是跟美國差不多？

Yes. Let me jump in first here. I don't think Murdo wants to take the tax part of that. So look, we're only moving it up by 50 basis points, Yaron. It's not related at all to the tax litigation. And just maybe that highlights the point that I should make in response to Geoff's [good] question a little bit earlier, which is why more commentary now. I think this is exactly why, because this is a complicated area for all of you, for the analysts. And we want to make sure you understand our position. We think that it's been a struggle to understand for folks based on prior conference calls. So we just want to be more specific on it.

是的。讓我先插一句。我認為默多不想捲入稅務問題。所以你看，我們只是上調50個基點，亞倫。這和稅務訴訟完全無關。也許這正好印證了我之前回答傑夫（Geoff）提出的那個好問題時應該補充的一點，這也是為什麼我現在要多解釋一下。我認為這正是原因所在，因為這對你們所有分析師來說都是一個複雜的問題。我們希望確保你們理解我們的立場。我們認為，根據之前的電話會議來看，大家可能很難理解。所以我們想更具體地說明一下。

But in the case of that question itself, it's not related at all. And again, Yaron, thanks for the question. We're confident in our position and the level of reserves where we're at. But we're wanting to provide some more background for you on it. So hopefully, that's helpful. And now I'll turn it over to Murdo to get back to business.

但就這個問題本身而言，它與此完全無關。再次感謝亞倫的提問。我們對目前的狀況和儲備水準充滿信心。但我們想向您提供更多背景資訊。希望這些資訊對您有所幫助。現在我將把發言權交給默多，讓他繼續討論正事。

Thanks, Peter. Yaron, I would say in the U.S., what we're seeing with LUMAKRAS is when that KRAS G12C status is known at the point of progression from first-line treatment to second line, we're getting over 80% of those patients to be treated by LUMAKRAS. So we're penetrating the population when the identification of the KRAS G12C status is there. So that's clearly the lever that we need to ensure improved. And as I answered Salveen's question earlier, this is really an account-by-account book of work. And we're doing it with urgency because we really can't have patients progressing from first line to second line and not have the choice of LUMAKRAS. So this is really important work that we're doing for patients.

謝謝，Peter。 Yaron，我想說，在美國，我們看到LUMAKRAS療法的進展是，當患者從第一線治療進展到二線治療時，如果已知KRAS G12C狀態，那麼超過80%的患者會接受LUMAKRAS治療。因此，當KRAS G12C狀態被辨識出來時，我們就能有效地將LUMAKRAS療法推廣到更多患者族群。這顯然是我們需要改進的關鍵。正如我之前回答Salveen的問題時所說，這確實是一項需要逐個病例進行的工作。我們正在以緊迫的步伐推進這項工作，因為我們不能讓患者在從一線治療進展到二線治療時，卻沒有LUMAKRAS療法的選擇。所以，我們正在為患者做著非常重要的工作。

When we look at the epidemiology of disease in the U.S. versus ex U.S., I would say that the overall incidence of non-small cell lung cancer is similar between the U.S. and Europe in terms of size. Now one thing just to think about as you go into Asia, as the incidence of KRAS G12C mutational status is a bit lower. If you take Japan as an example, it's about 4% of patients who have non-small cell lung cancer that also have a KRAS G12C mutation compared to 13% in the U.S. So the mutational epidemiology does change a little when you go outside of U.S. and Europe. So we would expect the business to be slightly bigger in the U.S. than it will be in Europe and rest of the world.

當我們比較美國和歐洲以外地區的疾病流行病學時，我認為美國和歐洲的非小細胞肺癌整體發生率規模相似。但要注意的是，亞洲地區KRAS G12C突變的發生率略低。以日本為例，約4%的非小細胞肺癌患者帶有KRAS G12C突變，而美國這一比例為13%。因此，在美國和歐洲以外地區，突變流行病學確實存在一些差異。所以我們預計，美國的市場規模會略大於歐洲和世界其他地區。

Your next question comes from the line of Umer Raffat from Evercore ISI.

你的下一個問題來自 Evercore ISI 的 Umer Raffat。

I guess two, if I may. First, perhaps on KRAS. There's an interesting disclosure on the slides on how 2,500 patients have taken it in U.S. commercially. And third-party data sets would suggest perhaps 1,200 patients were on the drug in March. And I'm trying to square those two. About 1,200 patients were on therapy in March and 2,500 is total exposure. Crude math would suggest that duration of therapy has tracked 5-ish months or so. Is that consistent with your observation?

我想問兩個問題，如果可以的話。首先，關於KRAS。幻燈片上披露了一個有趣的訊息，即在美國已有2500名患者服用過這種藥物。而第三方資料集顯示，3月可能有1,200名患者正在服用該藥物。我正在努力將這兩個數據連結起來。 3月份約有1200名患者正在接受治療，而2500是總暴露量。粗略計算一下，治療持續時間約為5個月左右。這與您的觀察結果一致嗎？

And then secondly, Peter, on the tax court side, can you guide us through what the time line could look like? Because I feel like this is one of those topics. Now there's a -- two sets of liabilities that people will put in their model somehow at certain probability and having a sense for what the time line could look like for resolution, or at the very least, on when the hearing is or when a key court date is coming up on the tax court, that would be very helpful.

其次，Peter，從稅務法庭的角度來看，您能否為我們介紹可能的流程時間表？因為我覺得這很重要。現在，人們會根據一定的機率在他們的模型中考慮兩類負債，如果能大致了解問題的解決時間表，或者至少知道聽證會的時間或稅務法庭的關鍵開庭日期，那就非常有幫助了。

Yes. Perhaps on the first question regarding patient numbers and duration of therapy. I think it's a little bit premature to be able to draw conclusions from numbers on drug versus numbers treated to get to DOT or duration of therapy. What you need to understand, I guess, in the 2,500 patients is we've got a combination of patients who were very late-stage disease, third line and beyond potentially, who were challenged with the product and didn't do very well. Whereas the steady state will be more second-line patients having experienced maybe one prior line of therapy who could do quite well as indicated by the long-term follow-up data that we just put out at AACR, where you see about 1/3 of patients being alive at the 2-year follow-up mark.

是的。關於第一個問題，即患者數量和治療持續時間，我認為現在根據藥物數量和達到治療持續時間（DOT）的患者數量得出結論還為時過早。我想您需要理解的是，在這2500名患者中，既有晚期患者，可能接受過三線或更長時間的治療，他們使用該藥物後療效不佳。而穩定期患者則更多是二線患者，他們可能接受過一線或更長時間的治療，療效可能相當不錯，正如我們剛剛在AACR會議上發布的長期隨訪數據顯示的那樣，大約三分之一的患者在兩年隨訪時仍然存活。

So I think it's too early to infer from existing in-market patient numbers to understand what the effective duration of therapy will be. And in fact, I often say this is you really actually need 24 months in market to understand what your look-back period is, to understand what your duration of therapy is. So it's going to be quite some time before we know what our real-world duration of therapy will be.

所以我認為現在就根據現有市場患者數量來推斷有效療程還為時過早。事實上，我常說，你真的需要24個月的市場觀察期才能了解回溯期，才能確定療程。因此，我們還需要相當長的時間才能知道實際的療程持續時間。

Umer, Peter here. So on the tax side, thank you. In terms of next steps and time line, we will be filing a petition with the U.S. Tax Court within 90 days. And as I mentioned, we will vigorously contest 2013 through 2015 notice through the judicial process. We plan to see consolidation of the 2013-2015 period with the ongoing 2010 to 2012 tax court case. And as I said, it will take several years for this to resolve itself. So that's the current time frame as we see it.

我是彼得，烏默。關於稅務方面，謝謝。關於下一步的計劃和時間表，我們將在90天內向美國稅務法院提交請願書。正如我之前提到的，我們將透過司法程序對2013年至2015年的稅務通知提出強有力的異議。我們計劃將2013年至2015年期間的稅務問題與正在進行的2010年至2012年稅務案件合併審理。正如我所說，這個問題需要幾年時間才能解決。這就是我們目前預計的時間安排。

Your next question comes from the line of Carter Gould from Barclays.

你的下一個問題來自巴克萊銀行的卡特·古爾德。

Maybe to focus for a second on TEZSPIRE. I was looking to get a little bit more color there, specifically how you think about the importance of the J code there and the extent that could drive an inflection in sales and I guess to the extent that's been an impediment to date. And then obviously, you started WAYFINDER recently. In the past, you guys kind of talked down the importance of the SOURCE results. So as we think about WAYFINDER, is that sort of critical in addressing that gap or simply a nice to have? Some color there would be helpful.

或許我們可以先重點談談TEZSPIRE。我想更深入地了解一下，特別是您如何看待J代碼的重要性，以及它在多大程度上能夠推動銷售成長，以及它迄今為止在多大程度上阻礙了銷售。另外，您最近推出了WAYFINDER。過去，您似乎不太重視SOURCE結果。那麼，在考慮WAYFINDER時，SOURCE結果對於彌合差距至關重要，還是只是錦上添花？如果能詳細解釋一下就太好了。

Thanks, Carter. On the question regarding TEZSPIRE, we're really excited about the market response to TEZSPIRE by having such a novel, unique product where the profile really simplifies the treatment of severe uncontrolled asthma, particularly for pulmonologists who have so much else to do that they're looking for a simple solution that can treat their patients without being limited by phenotypic or biomarker status. So overall, we think it's going really well.

謝謝卡特。關於TEZSPIRE的問題，我們對TEZSPIRE的市場反應感到非常興奮。 TEZSPIRE是一款新穎獨特的產品，其獨特的特性大大簡化了重度難治性氣喘的治療，尤其對於那些工作繁忙、急需一種不受表型或生物標誌物限制的簡便治療方案的肺科醫生來說，TEZSPIRE無疑是理想之選。總而言之，我們認為TEZSPIRE的進展非常順利。

It's clearly a benefit to have a permanent J code in the market, which, as I mentioned, this will be coming July 1. That gives confidence to providers and to their billing staff that they can code the product appropriately and have a high degree of assurance on reimbursement. I think they know the reimbursement is happening now, but it's also time to reimbursement for some of these practices. Some of them run pretty tight cash flows. And knowing that the permanent J code should expedite the time to reimbursement will actually help. So yes, I'd say it's going to be helpful.

市場上擁有一個永久性的J代碼顯然是件好事，正如我之前提到的，它將於7月1日正式生效。這讓醫療服務提供者及其計費人員更有信心，他們可以正確地對產品進行編碼，並對報銷更有保障。我認為他們現在就知道報銷即將開始，但對一些診所來說，現在也是時候獲得報銷了。有些診所的現金流非常緊張。而知道永久性J代碼能夠加快報銷速度，確實會有所幫助。所以，是的，我認為這將大有裨益。

But I would say that the in-market response currently is really good. And we're clearly providing product to patients who are going through that reimbursement step in that process so that they can get on therapy and have access to the medicine. But yes, we'd be looking for additional sales force -- sales growth in the back half of the year.

但我認為，目前市場反應非常好。我們顯然正在為正在辦理報銷手續的患者提供產品，讓他們能夠接受治療並獲得藥物。不過，我們確實需要擴充銷售團隊－以期在下半年達到銷售成長。

Yes, Carter. And in terms of WAYFINDER, this trial, we believe, will address some of the methodologic limitations, we believe we saw in the SOURCE trial. The sample size is much larger. It's a single-arm trial, sample size over 300 patients. Patients can be on a higher dose of steroids. There can be a more rapid corticosteroid taper. And we're looking at the effects earlier at earlier time points. All of these, I think, give us confidence that we will see effectiveness of TEZSPIRE in the setting of lowering oral corticosteroid use.

是的，卡特。就WAYFINDER試驗而言，我們相信這項試驗將解決我們在SOURCE試驗中發現的一些方法學限制。樣本數較大，這是一項單臂試驗，樣本數超過300名患者。患者可以接受較高劑量的類固醇治療，皮質類固醇的減量速度也可以更快。而且，我們會在更早的時間點觀察療效。我認為，所有這些因素都讓我們有信心，TEZSPIRE在降低口服皮質類固醇用量方面將有效。

In addition, we presented recently at the AAAAI meeting updated data from NAVIGATOR and other trials showing a very profound reduction in exacerbations in patients on oral corticosteroids. Again, I think this is going to be a really important drug for the treatment of asthma across a range of phenotypes, and we're quite confident in the development program going forward.

此外，我們最近在AAAAI會議上發表了NAVIGATOR試驗和其他試驗的最新數據，數據顯示口服糖皮質激素治療的患者氣喘急性發作次數顯著減少。我認為，對於治療各種表型的氣喘而言，這將成為一種非常重要的藥物，我們對未來的研發計畫充滿信心。

Next question comes from the line of Robyn Karnauskas from Truist.

下一個問題來自 Truist 的 Robyn Karnauskas。

So just a couple on Repatha. So just your thoughts on inclisiran with the permanent J code coming in July and your thoughts on the impact on Repatha in the second half of the year. And then just the second, you have impressive growth with Repatha. Maybe you could give a little bit more color on script trends by doctor. Are you seeing more scripts by cardiologists? What are some trends that give you confidence that, that growth can continue as far as who is prescribing the drug versus, I think, previously in the early days, it was lipidologists mainly?

關於瑞百安（Repatha），我有幾個問題想請教。首先，您能否談談即將於7月生效的永久性J代碼的英克立西蘭（Inclisiran），以及它對瑞百安下半年業績的影響？其次，瑞百安的成長動能非常強勁。能否詳細介紹不同醫師的處方趨勢？您是否看到心臟科醫師的處方量增加？有哪些趨勢讓您相信這種成長動能持續？就處方醫師而言，與早期主要由血脂專家開立處方的情況相比，有哪些變化？

Thanks, Robyn. We are pleased with the evolution of Repatha. The growth is actually fairly consistent across the broad cardiology community. So it's not just your lipidologist, a variety of cardiologists. We're seeing general community cardiologists. We also have a large effort focused on integrated delivery networks and hospital systems where we have been successful in establishing a more standardized way of treating the some 25 million high-risk ASCVD patients in the U.S. that end up in an acute care facility for their MI or other event that they've been admitted for.

謝謝，Robyn。我們對Repatha的發展感到滿意。事實上，整個心臟病學界的成長都相當穩定。因此，不僅是脂質專家，還有各種類型的心臟病專家，包括普通社區心臟病專家。我們也大力致力於整合醫療服務網絡和醫院系統，成功地為美國約2500萬因心肌梗塞或其他事件入院的高風險ASCVD患者建立了一套更標準化的治療方案。

And unfortunately, many of them don't even get a lipid panel, and many of them get discharged without appropriate recommendations or initiation of treatment. So we've stepped that up quite a bit, and we're seeing improvements in quality of care. And those patients are being discharged then to the community cardiologists and/or primary care physicians with clearer intent on more aggressive lipid-lowering therapy or cardiovascular risk reduction. So that's definitely helping.

不幸的是，許多患者甚至沒有做血脂檢查，許多患者出院時也沒有得到適當的建議或開始治療。因此，我們大幅加強了這方面的工作，並且看到了醫療品質的改善。這些患者出院後會被轉交給社區心臟科醫師和/或初級保健醫生，以便更積極地接受降血脂治療或降低心血管風險。所以，這無疑起到了積極作用。

For future growth, we're obviously going to continue that effort, and we're going to continue to expand that IDN work that we're going to do in the U.S. But we're also going to invest incrementally in primary care given that we're seeing some spontaneous prescribing with primary care. So we're very pleased with the growth of Repatha.

為了未來的成長，我們顯然會繼續努力，並繼續擴大我們在美國開展的IDN（整合醫療網絡）工作。同時，鑑於我們觀察到一些初級保健機構出現了自發性處方，我們也會逐步增加對初級保健的投入。因此，我們對Repatha的成長非常滿意。

Ex U.S., the other thing I would mention is we got the Jan 1 listing for Repatha in the China National Reimbursement Drug List, which has been a good launch for us there. And our team in China is doing a nice job of ensuring that Repatha is an option for high-risk ASCVD patients in that country. So really, I think we've got a large amount of headroom for growth on this product. There's a large patient population, and we've got good momentum now in cardiology, and we need to continue to build that into primary care and around the world.

除了美國以外，我還想提一下，瑞百安（Repatha）已於1月1日被納入中國國家醫保藥品目錄，這對我們來說是一個不錯的開局。我們在中國團隊的工作卓有成效，確保瑞百安能夠成為中國高風險動脈粥狀硬化性心血管疾病（ASCVD）患者的一種治療選擇。因此，我認為這款產品還有很大的成長空間。中國擁有龐大的患者群體，我們在心臟病領域也取得了良好的發展勢頭，我們需要繼續將其推廣到基層醫療和全球市場。

With respect to inclisiran, obviously, they're a competitor in the market. But given that they don't yet have event reduction data, even with reimbursement coding, I think they're still limited on what they can promote. But again, there's tons of patients out there that need more aggressive lipid-lowering therapy and more aggressive cardiovascular risk reduction, and we see that the market can bear a lot of people talking about this severe disease, the #1 killer in the world for everybody that's concerned about patients and what we can do about it. So overall, we're still very bullish.

就Inclisiran而言，顯然，他們是市場上的競爭對手。但鑑於他們目前還沒有事件減少方面的數據，即使有了醫療保險報銷編碼，我認為他們的宣傳力度仍然有限​​。不過，還有很多患者需要更積極的降脂治療和更積極的心血管風險降低方案，我們看到，市場能夠承受很多人談論這種嚴重的疾病——它是全球頭號殺手，每個人都關心患者以及我們能做些什麼。所以總的來說，我們還是非常看好Inclisiran。

RJ, I know we've got several callers still hoping to ask questions. And I just want to give the callers a heads up that we'll probably go a few minutes over the top of the hour. So why don't we take the next question, and we'll do our best to get to everybody. And if we're unable to do that, then we'll -- obviously, Arvind and his team will be available later.

RJ，我知道還有幾位聽眾想提問。我先提醒一下，我們可能會超時幾分鐘。所以我們先回答下一個問題，我們會盡力回答每位聽眾的問題。如果實在無法做到，那麼──當然，Arvind和他的團隊稍後會繼續解答。

Your next question comes from the line of Mohit Bansal from Wells Fargo.

你的下一個問題來自富國銀行的莫希特·班薩爾。

Maybe a question on TEZSPIRE. So given that right now, it needs to be administered by a provider, do you -- what kind of reservation do you expect from the doctors at this point in terms of prescribing the agent, given that Dupi is available for self-administration? And the question is, is there a possibility in the future that you could come up with a self-administration injection which could actually help it become a self-administered at-home product?

或許可以問一個關於TEZSPIRE的問題。鑑於目前它需要由醫護人員注射，考慮到Dupi可以自行注射，您認為醫生在開立TEZSPIRE處方時會有哪些顧慮？另外，未來是否有可能研發出一種可以自行注射的藥物，使其真正成為一種可以在家中自行注射的產品？

Thanks, Mohit. The -- unfortunately, because severe asthma, especially uncontrolled severe asthma, is such an acute condition, many of these patients are under frequent care of a pulmonologist or an allergist. And so they're seeing their physician on a very regular basis. And I think given our very convenient once a month dosing, it's seen as a fairly easy product to administer. And of course, it's early days in the launch, but the feedback has been that the physician administration is not a barrier to initiation of TEZSPIRE. And allergists, in particular, are used to physician-administered products.

謝謝，莫希特。 ——遺憾的是，由於重度氣喘，尤其是未控制的重度氣喘，病情非常緊急，許多患者需要頻繁地接受肺科醫師或過敏科醫師的診治。因此，他們需要定期就診。我認為，鑑於我們每月一次的便捷給藥方式，這款產品被認為使用起來相當容易。當然，目前產品上市尚處於早期階段，但回饋表明，醫師給藥並非啟動TEZSPIRE治療的障礙。特別是過敏科醫生，他們已經習慣了醫生給藥的治療方式。

What I think the benefit side of this is really playing out is that they have much less work to do on the biomarker side or the phenotypic assessment side. And so we've simplified their workflow in that regard. I do think over the long haul, we'll continue to evaluate what we need to do to ensure that there's convenience and maintenance for patients. And obviously, we're looking at other indications and other life cycle opportunities for TEZSPIRE. So we'll continue to assess whether or not we want to provide a self-administered option. I mean, clearly, the product could be developed that way, and we continue to look at that.

我認為這項措施的真正優勢在於，他們在生物標記或表型評估方面的工作量大大減少。因此，我們簡化了他們在這方面的工作流程。從長遠來看，我們將繼續評估需要做些什麼，以確保患者能夠方便地使用和維持治療。顯然，我們也在探索TEZSPIRE的其他適應症和其他生命週期機會。因此，我們將繼續評估是否要提供一種自我給藥方案。我的意思是，顯然，該產品可以朝著這個方向開發，我們也將繼續研究這方面。

Your next question comes from the line of Dane Leone from Raymond James.

你的下一個問題來自 Raymond James 的 Dane Leone 的產品線。

Congrats on the quarter. One question for me. Presuming the dose equivalency study of LUMAKRAS actually demonstrates that 240-milligram Q day is equivalent to 960, how are you planning on managing that transition at the end of the year? And the reason we get this question a lot from investors is, obviously, that will coincide with the presumed launch of a competitor in the KRAS G12C space. Maybe to frame it just from a script being given, a 30-day script being given at the end of the year, if this dose equivalency does show that lower dose is equivalently effective, that 30-day script turns into a 120-day script. Just how is your team thinking of managing this? And is there any expected change to pricing that would be enacted if the lower dose is seen as equivalent?

恭喜貴公司本季業績優異。我有一個問題。假設LUMAKRAS的劑量等效性研究確實表明，每日240毫克與960毫克療效相當，那麼你們計劃如何在年底應對劑量調整？我們經常收到投資者的這個問題，原因顯而易見，因為這將與KRAS G12C領域競爭對手的上市時間重疊。假設年底開立的處方是30天的療程，如果劑量等效性研究確實顯示較低劑量同樣有效，那麼30天的療程將變為120天的療程。貴公司團隊是如何考慮應對這種情況的？如果較低劑量被證實療效相當，價格方面是否會有任何調整？

Yes, it's a pretty detailed hypothetical. What I would say is, first off, we remain confident that the 960-milligram dose is the right dose. And clearly, the safety and efficacy benefit of that product looks very good. And given the long-term follow-up data, clearly, it's a high bar for us to be able to see if it can be approved upon at a lower dose. So that's the one question that remains to be answered.

是的，這是一個相當詳細的假設。首先，我們仍然堅信960毫克的劑量是適當的。顯然，該產品的安全性和有效性都非常出色。鑑於長期追蹤數據，要確定其能否以更低的劑量獲批上市，顯然是一個很高的門檻。所以，這是目前唯一需要解答的問題。

The way, I guess -- I can't directly answer your question because there's so many different complicated variables to it. But what I would say is we continue to look at the best way to provide the right treatment for continuing patients. So if you're a second-line non-small cell lung cancer patient, you've been prescribed LUMAKRAS at 960, you're taking it, you've responded and you're stable, I'm not sure any oncologist is going to want to lower your dose if you're a continuing patient. Now we've seen that in other disease areas where there might have been a dose change either that go up or that go down, where patients who are on a stable dose usually stay on that. So that would be my one bit of additional commentary to your question. But we'll wait and we'll see the data, and we'll handle it according to what the data say and what the FDA guides us to do.

我想我無法直接回答您的問題，因為它涉及太多複雜的變數。但我可以肯定的是，我們會繼續尋找為持續接受治療的患者提供最佳治療方案的方法。例如，如果您是二線非小細胞肺癌患者，醫生給您開了960毫克的LUMAKRAS，您正在服用，病情穩定且有療效，那麼我不確定是否有腫瘤科醫生會希望降低您的劑量。我們在其他疾病領域也看到類似的情況，劑量可能會有所調整，無論是增加或減少，但通常情況下，劑量穩定的患者會繼續維持目前的劑量。這就是我對您問題的補充說明。我們會等待數據，並根據數據和FDA的指導來處理。

Your next question comes from the line of Evan Seigerman from BMO Capital Markets.

你的下一個問題來自 BMO 資本市場的 Evan Seigerman。

I wanted to ask one from Murdo on Otezla now that we have the full label or kind of the full spectrum approval as of last December. So have you seen any sort of barriers for the more mild patients? Do these patients need to go through any sort of step edits or are they able to get it pretty freely? Do you expect that to change over the course of the year? Just love to get some color on how you're pushing it or marketing it in those patients.

我想問 Murdo 一個關於 Otezla 的問題，因為從去年 12 月起，我們已經獲得了該藥的完整適應症或類似全譜適應症的批准。您是否發現輕症患者在使用過程中遇到任何障礙？這些患者是否需要經過任何步驟審查，還是可以比較順利地取得該藥物？您預計這種情況在今年會有所改變嗎？我很想了解您是如何向這些患者推廣或宣傳該藥的。

Thanks for the question, Evan. No, we're really pleased with the response from payers and PBMs to ensuring that the expanded label now, regardless of severity of psoriasis, that patients can have strong access and good affordability for the product. In fact, we've actually improved access this year versus last year. So we've been able to produce some of the prior authorization criteria, things like percentage of body surface area. There are some medical policies, prior authorizations where that's described as a percentage. We've had many of those removed. So we've actually opened up access for those patients. And I think that [it's easier] to prescribe Otezla for that milder patient.

謝謝你的提問，Evan。是的，我們非常高興看到支付方和藥品福利管理機構（PBM）積極回應，確保無論銀屑病的嚴重程度如何，患者都能便捷地獲得價格合理的藥品。事實上，今年的藥品可近性比去年有所提高。我們簡化了一些預先授權標準，例如體表面積百分比。有些醫療政策和預先授權要求以百分比來描述用藥情況。我們已經取消了許多此類要求。因此，我們實際上為這些患者打開了用藥管道。我認為，對於病情較輕的患者來說，開立Otezla處方也更容易了。

I was at the American Academy of Dermatology meeting in March and spoke to many dermatologists and asked them what their prescribing experience was like and what the reimbursement experience was. And I think many of them played back to us that Otezla was easier than it had been in the past to prescribe for that milder patient. The other thing we did was we enhanced our co-pay assistance and our own bridging programs to ensure that, that launch would go well. So so far, so good. Off to a good start, but I don't anticipate access being an impediment.

三月我參加了美國皮膚病學會年會，和許多皮膚科醫生交流，詢問他們的處方經驗以及報銷情況。我覺得很多醫生都回饋說，現在給病情較輕的患者開Otezla比以前更容易了。我們也加強了共同支付援助和過渡性治療項目，以確保新藥上市順利進行。目前為止一切順利。開局不錯，我預計藥物可及性不會成為問題。

RJ, in consideration to the folks on the East Coast, it's past the hour. So why don't we take 2 more questions, please?

RJ，考慮到東海岸的朋友們，現在已經過整點了。那麼，我們能不能再回答兩個問題呢？

Your next question comes from the line of Cory Kasimov from JPMorgan.

你的下一個問題來自摩根大通的科里·卡西莫夫。

This is Gavin on for Cory. I just had a follow-up from a question earlier in the queue on LUMAKRAS-pembro combo data late in the summer. I guess just of the lung cancer patients, can you remind us if this is predominantly second line plus? Or will there be sufficient patients in the front line to assess the pathway or a path forward?

我是 Gavin，替 Cory 回答。我剛剛收到一個後續問題，是關於之前排隊等候的關於 LUMAKRAS-pembro 聯合療法在夏末公佈的數據。我想問的是，就肺癌患者而言，您能否提醒我們一下，這些數據主要來自二線及以上治療嗎？或者，第一線治療的患者是否足夠多，可以評估該療法的治療路徑或未來發展方向？

And then should we also look for multiple doses and/or different dosing administration? I think you've discussed in the past sequential dosing versus other strategies.

那麼，我們是否也應該考慮多劑量給藥和/或不同的給藥方式呢？我想您之前討論過序貫給藥與其他給藥策略的比較。

Yes. Thanks, Cory. Most of those patients will be second line and beyond. Maybe there is a limited experience in first line, and we are looking across a range of doses with both combination and sequential therapy. So you can expect to see all of that when the data are presented.

是的，謝謝，科里。這些患者大多是二線或更遠期的治療對象。一線治療的經驗可能有限，我們正在研究聯合治療和序貫治療的各種劑量方案。所以，您可以在數據公佈時看到所有這些資訊。

Let's take one last question, RJ. And after that, Bob is just going to make a couple of concluding comments.

RJ，我們最後一個問題。之後，鮑伯將作幾點總結性發言。

Your next question comes from the line of Colin Bristow from UBS.

你的下一個問題來自瑞銀集團的柯林布里斯托。

I'll keep this quick. Just quickly on the tax issues. Could you just talk about whether we should view this as being essentially limited to 2015? Or is there scope for this really to permeate through to effectively 2021?

我就長話短說。關於稅務問題，您能否談談我們是否應該認為這項政策基本上僅限於2015年？還是說它真的有可能持續到2021年？

And then just quickly on LUMAKRAS. There was a small investigator-led data set presented at ELCC a few weeks ago. We saw some relatively high rates of LFT elevations with LUMAKRAS dose in close sequence with PD-1. I was just curious how this compares to your own experience with the combo versus sequential dosing. And anything else you can say about the path forward there.

然後，我想簡單談談LUMAKRAS。幾週前在ELCC會議上，有一項由研究者主導的小型數據集被公佈。我們發現，LUMAKRAS與PD-1緊密合併用藥後，肝功能指標（LFT）升高的發生率相對較高。我很好奇這與您自身使用聯合用藥與序貫用藥的經驗相比如何。您對未來的研究方向還有其他看法嗎？

Colin, thank you. Look, on the case, we're very confident in the position we've had and our structure and how we've allocated profits between Puerto Rico and the United States. So we're very confident in those reserves. If you did think about going forward, I did suggest in the press release articulated that the IRS is currently auditing 2016 through '18. If they did propose any transfer pricing (inaudible) the magnitude of those adjustments will be lessened by the change in tax rate from the 2017 Tax Act, which reduce the differences between the tax rates applicable in the United States and Puerto Rico by approximately 2/3 beginning in 2018. But once again, we're very confident in how we're structured (inaudible), and we're very confident in the level of our reserves. And so we don't anticipate any changes going forward.

科林，謝謝。關於這個案子，我們對我們目前的狀況、組織架構以及在波多黎各和美國之間分配利潤的方式都非常有信心。所以我們對這些儲備金非常有信心。如果你考慮過未來的發展，我在新聞稿中提到過，美國國稅局目前正在對2016年至2018年進行審計。如果他們確實提出了任何轉讓定價方面的調整（聽不清楚），由於2017年稅法的稅率變化，這些調整的幅度將會減少。該稅法從2018年開始將美國和波多黎各適用稅率之間的差異減少了約三分之二。但是，再次強調，我們對我們目前的組織架構（聽不清楚）以及我們的儲備金水準都非常有信心。因此，我們預計未來不會有任何變化。

And Dave, do you want to catch the second piece of that?

戴夫，你想接住第二塊嗎？

Yes. With regards to the ELCC data, these were uncontrolled data from an investigator in France, patients receiving monotherapy potentially after checkpoint inhibitors. I can tell you that the rates of hepatic toxicity were higher than we have observed in our clinical trials program and through our ongoing pharmacovigilance effort. So I'm not sure why that was the case, but it was a heterogeneous unselected group of patients. It's hard for us to comment any further on those data.

是的。關於ELCC的數據，這些數據來自法國的一位研究者，屬於非對照研究，患者接受的是單藥治療，可能是在接受免疫檢查點抑制劑治療之後。我可以告訴你，肝毒性的發生率高於我們在臨床試驗計畫和持續性藥物警戒工作中觀察到的結果。所以我也不確定具體原因，但這是一群未經篩選的異質性患者。我們很難就這些數據做出更多評論。

Let me just thank all of you for dialing in. We appreciate your support and your interest in the company. As we've tried to convey through this call, we feel we're executing well here into the 2022 calendar year. And we look forward to being back together with you after the second quarter to report on our progress through the midyear. Thank you. Sorry, we went a few minutes over. Thanks.

首先，我要感謝各位撥入電話會議。我們非常感謝你們的支持和對公司的關注。正如我們在這次電話會議中一直強調的，我們認為公司在2022年全年的營運進展良好。我們期待在第二季結束後再次與大家見面，報告我們年中的進展。謝謝。抱歉，會議超時了幾分鐘。謝謝。

Thank you, everybody.

謝謝大家。

Ladies and gentlemen, this concludes today's conference call, and we thank you all for participating. You may now disconnect.

女士們、先生們，今天的電話會議到此結束，感謝各位的參與。現在可以斷開連線了。