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.

我叫 RJ，今天我將擔任安進公司 2022 年第一季度財務業績電話會議的會議主持人。 （操作員說明）我現在想介紹投資者關係副總裁 Arvind Sood。蘇德先生，您現在可以開始了。

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。謝謝你。大家下午好，歡迎來到我們的第一季度電話會議。我認為我們在第一季度的表現體現了我們繼續專注於執行，同時保持在實現我們長期目標的軌道上。所以讓我們開始吧。

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.

幻燈片已發布。快速提醒一下，我們將在演示文稿中使用非公認會計原則財務指標，其中一些陳述將是前瞻性陳述。我們向美國證券交易委員會提交的文件確定了可能導致我們的實際結果發生重大變化或差異的因素。

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

因此，我想將電話轉給我們的董事長兼首席執行官 Bob Bradway。鮑勃？

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。謝謝你，Arvind，大家好，謝謝你加入我們的電話。當我們在 2 月最後一次發言時，我們告訴過您，我們將專注於執行，並且我們有許多機會可以讓我們實現長期有吸引力的增長。

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，我們很好地把握了這些機會，實現了 6% 的收入增長和 15% 的每股收益增長。儘管在今年前 2 個月受到 COVID 的影響、貨幣逆風，當然還有淨售價下降，但我們仍實現了這一業績。

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 2 月份重點介紹的創新品牌在第一季度繼續實現強勁的銷量增長，其中 Repatha 增長了 49%； Prolia，上漲 10%；均勻度，上漲 59%；和 Otezla 增長 7%，我們的幾個腫瘤產品也在本季度產生了有吸引力的銷量增長。

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.

我們的 2 種最新創新藥物 LUMAKRAS 和 TEZSPIRE 已開始強勢開局，分別為患有非小細胞肺癌和嚴重哮喘的患者提供令人信服的新治療選擇。我們還在為這兩種產品尋求重要的新適應症。

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.

我只想說，關於我們在市場上擁有的 5 種高質量的生物仿製藥，它們表現良好，符合我們的預期。正如我們之前所指出的，隨著時間的推移，生物仿製藥產品組合的增長將通過新產品的穩步推出來實現，包括明年 1 月我們在美國推出的 HUMIRA 生物仿製藥 AMGEVITA。 AMGEVITA 是我們預計在本世紀末推出的 6 種新生物仿製藥中的第一種。

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.

國際增長是我們長期戰略的重要組成部分，第一季度我們在美國以外的地區實現了 15% 的強勁增長，在亞太地區實現了近 30% 的增長。

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.

轉向我們的管道。如您所知，我們正在推進在炎症、腫瘤學和普通醫學領域的許多中後期潛在的一流機會，同時繼續投資於我們的創新營銷品牌和生物仿製藥。自我們進行業務審查以來，我們已經獲得了 LUMAKRAS、Repatha 和 ABP 654 的重要數據讀數，這是我們對 STELARA 的 III 期生物仿製藥候選藥物。在今年餘下的時間裡，我們還有幾個數據里程碑。

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.

放眼長遠。我們繼續深思熟慮地投資於一整套發現研究能力，包括人類數據和生成生物學，因為我們希望顯著擴大我們可以追求的目標數量，縮短週期時間並增加我們成功的可能性。

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，無論是通過我們自己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在有機和創新方面進行投資通過業務發展。

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.

我們為患者服務的工作正值社會面臨許多挑戰之際，我們正在儘自己的一份力量來解決這些挑戰，正如我們在整個歷史上所做的那樣，重點關註四個領域：消除限制公平獲得醫療保健的障礙，努力建立一個更加公正的社會，最大限度地減少我們對環境的影響，並確保我們的行為和文化反映安進的價值觀。如果您有興趣了解更多信息，我們最新的環境、社會和治理報告於今天早些時候發布，可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.

在我轉向彼得之前，讓我先感謝我在世界各地的安進同事，感謝他們致力於為患者服務和出色的執行力。現在彼得，交給你了。

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.

謝謝你，鮑勃。隨著我們朝著長期目標邁進，我們對本季度的執行和增長感到滿意。在討論我們的 2022 年指導之前，我將介紹我們的第一季度財務業績。財務結果顯示在幻燈片的幻燈片 5 上。

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.

第一季度是另一個穩健執行的時期，收入同比增長 6%，非公認會計原則每股收益增長 15%。產品銷售方面，Repatha、Prolia 和 EVENITY 推動了 9% 的強勁銷量增長。銷量增長被淨售價下降和外匯逆風部分抵消。

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.

我們已建立的產品組合包括 EPOGEN、Aranesp、Neulasta、NEUPOGEN、Sensipar 和 Parsabiv，產生了近 10 億美元的產品銷售額，並繼續提供強勁的現金流。

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.

過渡到我們的生物仿製藥後，AMGEVITA 仍然是歐洲處方最多的阿達木單抗生物仿製藥。展望未來，我們將利用這一成功經驗，準備於 2023 年 1 月在美國推出和發展該產品。對於 MVASI 和 KANJINTI，正如預期的那樣，由於淨售價下降，我們經歷了同比下降，我們預計這些產品的這種趨勢將繼續下去。默多將在他的講話中更詳細地討論產品銷售。

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 5 億美元的收入同比增長 64%，主要受我們 COVID-19 抗體合作的推動。由於我們投資於我們的管道、執行產品發布和推動整個公司的數字化，第一季度非 GAAP 總運營費用同比增長 2%。在非公認會計原則基礎上，銷售成本佔產品銷售額的百分比同比增長 1.1 個百分點至 16.6%，主要是由於直接製造成本、COVID-19 抗體製造成本和特許權使用費增加以及利潤份額。本季度非 GAAP 研發支出同比下降 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.

回想一下，2021 年第一季度包括與我們收購 Rodeo Therapeutics 相關的 5300 萬美元。不包括 2021 年 Rodeo 的 5300 萬美元，非 GAAP 研發同比增長 5%。第一季度非 GAAP SG&A 費用同比下降 1%。我們將繼續專注於優先考慮關鍵投資和活動以及提高生產力。

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.

非美國通用會計準則其他收入和支出在第一季度淨支出為 4.13 億美元。由於我們使用權益會計法，該項目由利息費用和我們在百濟神州業績中的份額驅動。我們擁有強大的資產負債表，產生大量現金流，並保持出色的財務靈活性來評估戰略業務發展機會。

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.

我們繼續執行我們的資本配置優先事項。首先，投資於內部和外部的最佳創新；其次，通過資本支出投資我們的業務，包括在俄亥俄州和北卡羅來納州正在建設的新環保設施；第三，通過增加股息向股東返還資本，包括本季度每股 1.94 美元，較 2021 年第四季度增長 10%；第四，機會性股票回購，包括第一季度2460萬股普通股，其中包括根據加速股票回購協議收到和退休的2330萬股初始股。

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.

談到 2022 年的業務前景。我們對 2022 年迄今為止的增長感到滿意，我們正在跟踪我們的 2022 年計劃。因此，我們重申我們的 2022 年指引，收入範圍為 254 億美元至 265 億美元，非公認會計準則每股收益範圍為 17 美元至 18 美元。該非公認會計原則每股收益指南不包括未來某些類型的交易可能產生的前期費用。與我們的同行類似，我們更新了我們的非 GAAP 政策，根據美國證券交易委員會最近發布的指南，不再將此類費用從我們的非 GAAP 業績中排除。

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，當我們重新預測 2021 年以納入這一變化時，唯一的影響是我們的非公認會計原則運營費用現在將包括 2021 年之前排除的兩項項目。首先，記錄並獲得了 15 億美元與五個 Prime 相關的進行中的研發2021 年第二季度收購。第二，與 2021 年第三季度從 Kyowa Kirin Co. 獲得 AMG 451 許可權的預付款有關的研發記錄了 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.

2022 年剩餘時間需要考慮的重要附加點。外匯對我們 2022 年第一季度的銷售額產生了不利影響，根據目前的匯率，預計這將對我們報告的產品銷售額同比產生約 4 億美元的不利影響，並且已包含在我們的指導中。我們注意到，雖然我們的對沖計劃的結果在產品銷售中報告，但我們的對沖計劃旨在部分減輕外匯對我們全年淨收入的影響。總的來說，我們的 2022 年非公認會計原則每股收益指引包括約 2% 或約 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%.

我們繼續預計 2022 年的其他收入將在 14 億美元至 17 億美元之間。第一季度包括我們與 COVID 合作的大部分全年預計收入，並記得 2021 年的這些收入在第二季度至第四季度得到確認。我們的 COVID 合作收入前景取決於大流行的狀況和政府的持續支持。我們對 2022 年非 GAAP 總運營費用的預期與我們上次談話時沒有變化。然而，當與我們重鑄的 2021 年結果進行比較時，非公認會計原則的總運營費用現在將反映出同比低兩位數的下降。我們繼續預計 2022 年營業利潤率佔產品銷售額的百分比約為 50%。我們繼續預計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 年非公認會計原則研發費用的預期保持不變。根據我們重鑄的 2021 年結果，作為對上述 SEC 指導的回應，2021 年非 GAAP 研發費用增加了 4 億美元，我們預計 2022 年非 GAAP 研發費用現在相當於下降 4% 至 6% -超過一年。我們繼續預計 SG&A 支出佔產品銷售額的百分比將與去年持平。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，這反映了利率上升和我們在百濟神州業績中的份額。這是從我們之前的 14 億美元到 16 億美元的變化。

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，我們預計非公認會計原則稅率範圍為 13.5% 至 14.5%，高於我們之前的 13% 至 14% 的指導。

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.

您有機會閱讀我們與美國國稅局就 2010 年至 2015 年期間擬議調整的訴訟和爭議的更新，包括在新聞稿中。我們堅信，國稅局提出的那個時期的調整和國稅局提出的 2013 年至 2015 年期間的處罰是沒有根據的。

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 年期間的調整金額誇大了爭議的規模數十億美元。我們於 2021 年 7 月向美國稅務法院提交了一份請願書，對之前針對 2010 年至 2012 年期間提出的調整提出異議。我們計劃向美國稅務法院提交另一份請願書，對通知中提出的 2013 年至 2015 年期間的調整提出異議。這場爭端預計需要數年時間才能解決。

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.

Amgen 認為 IRS 聲稱在 2013 年至 2015 年期間罰款約 20 億美元是完全沒有根據的。自 2002 年以來，我們一直採用一致的轉讓定價方法。我們已經記錄了相關稅收法規要求轉讓定價方法，並在多個納稅年度的多次稅務審計中與 IRS 廣泛討論了該方法。美國國稅局此前從未提出過轉讓定價處罰。

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.

安進還認為，根據美國國稅局提出的立場，由於美國國稅局未能考慮某些收入和支出，2010 年至 2015 年期間的美國國稅局調整被誇大了約 20 億美元。多年來，安進一直以一致的方式報告其收入和支出，美國國稅局在所有先前的審計中都對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 年期間可能征收的任何額外稅款都將減少多達約 31 億美元的先前與公司波多黎各收益相關的匯回稅。安進此前在 2010 年至 2015 年期間向 IRS 預繳了總計 11 億美元的預繳稅款。這些存款將進一步減少可能征收的任何額外現金稅。

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審計 2016 年至 2018 年期間。我們預計審計將持續數年，並且有可能在 2016 年至 2018 年審計和行政上訴程序結束之前解決 2010 年至 2015 年的爭議。 IRS 可能在此期間提出的任何轉讓定價調整將因 2017 年稅制改革法導致的稅率變化而減少，該法從 2017 年開始將美國和波多黎各適用的稅率之間的差異減少了大約 2/3 2018 年。

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.

我們對自己在訴訟和爭議中的立場充滿信心。我們感謝我們在波多黎各的所有高技能同事以及他們對安進為患者服務的使命所做的重要和持續的貢獻。現在回到每次為每位患者服務的使命。鑑於業務的實力以及我們由 24,000 名每天為患者提供服務的優秀而敬業的團隊，我們對安進公司的長期增長充滿信心。

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

財務更新到此結束。我現在把它交給默多。

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，彼得。第一季度產品銷售額同比增長 2%。我們繼續推進以銷量為導向的增長戰略，這導致第一季度全球銷量增長了 9%。我們為 Repatha、EVENITY 和 BLINCYTO 實現了創紀錄的季度銷售額；以及包括 Prolia、KYPROLIS 和 AMGEVITA 在內的幾種其他產品的兩位數銷量增長。

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 2 個月，COVID-19 影響了我們在美國和世界各地的業務，因為 Omicron 變體導致醫療保健部門的產能下降，並減少了我們自己的銷售人員的工作日。 3 月並持續到 4 月，Omicron 在美國的影響減弱，這使我們能夠參與更多的面對面客戶互動。提供者和患者的活動也有所增加，從而導致對我們產品的需求有所改善。

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.

現在讓我回顧一些產品細節，從我們的普通藥物組合開始，包括 Prolia、EVENITY、Repatha 和 Aimovig。我們的普通醫藥產品組合的總收入同比增長 19%，銷量增長 23%。在骨骼健康方面，Prolia 的銷售額同比增長 12%。由於新患者和重複患者的增加，銷量增長了 10%。在我們的骨骼產品組合中補充 Prolia 的 EVENITY 在我們市場的強勁銷量增長的推動下，本季度的銷售額達到了創紀錄的 1.7 億美元。

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.

移至 PCSK9 級別的全球領導者 Repatha。在銷量增長 49% 的推動下，Repatha 的銷售額同比增長 15%。在美國，我們看到了 41% 的銷量增長。淨售價下降，因為我們提供更高的回扣以支持廣泛的醫療保險 D 部分和商業患者准入。從 1 月 1 日開始，Repatha 被納入中國國家報銷藥品目錄，銷售額增長 12%，銷量增長強勁。我們仍然專注於提高 Repatha 在全球的市場滲透率，以解決治療高危心血管疾病方面未得到滿足的重大醫療需求患者。

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.

轉到我們的炎症產品組合。 Otezla 在第一季度實現了 7% 的同比銷量增長。在美國，我們看到市場走強，Otezla 仍然是市場領導者，在新使用系統性銀屑病藥物的患者中佔有 30% 的份額。 Otezla 最近擴大的標籤受到了付款人、提供者和患者的好評。我們正在看到醫生對輕度銀屑病患者使用更多系統性治療的早期跡象，並且大多數皮膚科醫生預計會增加使用 Otezla 治療輕度銀屑病。

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.

在全球範圍內，由於美國批發和專業藥品渠道的淨價格下降和庫存水平下降，Otezla 銷售額同比下降 5%。 Otezla 在美國的淨價格下降主要是由於我們加強了共同支付和過渡計劃以支持新患者開始治療。展望未來，我們預計 2022 年剩餘季度的價格同比下降幅度會降低。我們還預計，由於無論銀屑病的嚴重程度如何，我們都有獨特的廣泛適應症，因此更廣泛採用 Otezla 將推動銷量持續增長。

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.

由於淨售價和庫存水平下降，ENBREL 第一季度銷售額同比下降 7%。在 ENBREL 長期的療效和安全性記錄的支持下，第一季度的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.

我們推出的 TEZSPIRE 開局良好，第一季度銷售額為 700 萬美元。付款人、提供者和患者的初步反饋非常積極。在我們的疾病狀態教育計劃的支持下，自推出以來，醫生的獨立意識提高到 65% 以上。在訪問方面，TEZSPIRE 是一種醫療福利產品，我們預計截至今年 7 月 1 日將對其進行永久報銷編碼。過敏症學家和肺病學家都承認 TEZSPIRE 獨特的差異化特性及其廣泛的潛力，可用於治療全球 250 萬不受控製或符合生物學條件且沒有任何表型和生物標誌物限制的嚴重哮喘患者。

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%.

轉向血液學和腫瘤學業務。我們的 6 款創新產品同比增長 17%，銷量增長 11%。我們看到 KYPROLIS、Nplate 和 BLINCYTO 的銷量增長強勁，我們預計這一趨勢將持續到今年。 XGEVA 銷售額同比增長 7%，而銷量下降 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.

我們推出的 LUMAKRAS 進展順利，第一季度收入為 6200 萬美元，環比增長 38%。在美國，自推出以來，已有超過 1,500 名醫生在學術和社區環境中為大約 2,500 名患者開具 LUMAKRAS 處方。雖然美國約有 80% 的患者接受了 KRAS G12C 狀態檢測，但當患者進展超過一線治療時，檢測結果並不總是可用和/或審查。

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.

改善護理的機會是確保 KRAS G12C 狀態在患者圖表或電子病歷中可用，並由腫瘤科醫生審查，以確保 LUMAKRAS 被討論為患者的選擇。 LUMAKRAS 在美國擁有強大的付款人覆蓋率，93% 的患者可以使用處方集。在美國以外，sotorasib 現已在全球近 40 個國家獲得批准，最近在英國和日本獲得了報銷批准。

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.

我們的腫瘤生物仿製藥銷售額同比下降 25%。雖然我們的生物仿製藥 MVASI 和 KANJINTI 均佔據領先地位，但由於競爭加劇和平均售價下降，我們預計淨售價將繼續惡化，銷量將繼續下降。隨著時間的推移，我們預計我們的生物仿製藥業務的長期增長將受到新分子的添加和從 2023 年 1 月在美國 AMGEVITA 開始的額外推出的推動。

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

總體而言，我們的增長戰略執行得很好，我們的投資組合擁有強勁的銷量趨勢。有了這個，我會把它交給戴夫。

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，默多。大家下午好。第一季度是研發的持續執行之一，我們專注於推進我們強大的創新臨床管道，其中包括許多潛在的一流機會。從炎症開始，我們啟動了 TEZSPIRE 治療嚴重哮喘的另外 2 項研究：WAYFINDER IIIb 期研究，旨在證明長期口服皮質類固醇治療的成年參與者的口服皮質類固醇使用減少；以及 PASSAGE IV 期真實世界有效性研究，旨在評估成人和青少年參與者的 TEZSPIRE，包括代表性不足的人群，如美國黑人、吸煙者和哮喘-COPD 重疊患者。

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 的 III 期計劃繼續進行，以前的 AMG 451 是一種抗 OX40 單克隆抗體，正在異質性中度至重度特應性皮炎患者中進行研究。 Rocatinlimab 結合激活的表達 OX40 的致病性 T 細胞。通過其獨特的作用機制，rocatinlimab 可抑制和阻止活化的致病性 T 細胞的擴增並減少其數量。因此，rocatinlimab 有可能導致深刻的疾病控制。此外，這為更長的給藥間隔提供了理由，並有望實現疾病改善。 ROCKET 是全面的 rocatinlimab III 期計劃，仍有望在 2022 年年中啟動。

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.

在我們的生物仿製藥產品組合中，上週，我們公佈了一項 III 期研究的初步結果，該研究評估了 ABP 654 與 STELARA 優特克單抗在成人中度至重度斑塊型銀屑病患者中的療效和安全性。該研究達到了主要療效終點，表明 ABP 654 和 STELARA 之間沒有臨床意義的差異。

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.

現在轉向腫瘤學。本月早些時候，我們在 AACR 上展示了 LUMAKRAS CodeBreaK 100 試驗的 2 年分析結果數據，該試驗證明了長期臨床益處，包括接受治療的 KRAS G12C 突變晚期非小細胞肺癌患者的總生存期與LUMAKRAS。這些數據顯示，大約 1/3 的患者在 2 年內仍然存活，並且通過中央審查觀察到延長的腫瘤反應，客觀反應率為 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.

雖然這是一項沒有對照組的單臂試驗，但療效數據與基於歷史數據的該患者群體的預期結果相比是有利的。在為期 2 年的跟踪分析過程中，沒有報告新的安全信號。我們已向夏末舉行的醫學大會提交了 LUMAKRAS PD-1 組合和 SHIP2 組合隊列的數據，而 LUMAKRAS 確認性 III 期研究與多西紫杉醇的一線結果以及劑量比較研究的第三季度和Q4，分別。

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.

同樣在肺癌領域，我們已向夏末舉行的醫學大會提交了 tarlatamab 的更新 I 期數據，我們的 DLL3 靶向半衰期延長 BiTE 分子用於復發/難治性小細胞肺癌患者。我們計劃在本季度啟動 DeLLphi-303，這是一項 Ib 期研究，測試 tarlatamab 與一線小細胞肺癌的護理標準相結合。

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加 bemarituzumab 的 Ib 期研究，bemarituzumab 是一種針對 FGFR2b 的單克隆抗體。

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.

轉向胃腸癌。我們在 2 月份的 ASCO 全體會議上展示了數據，其中 LUMAKRAS 在 38 名經過大量預處理的晚期胰腺癌患者中證實了 21% 的客觀緩解率和 84% 的疾病控制率。我們繼續探索 LUMAKRAS 作為單一療法以及在這種情況下與其他藥物聯合使用時的益處。

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.

在三線結直腸癌中，LUMAKRAS 與 Vectibix 聯合的 III 期研究正在招募患者。在胃癌中，貝馬妥珠單抗聯合口服化療方案治療 FGFR2b 過表達腫瘤的 Ib 期研究已經啟動。

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.

在普通醫學領域，我們很高興地宣布 2 項 Repatha 開放標籤擴展試驗的結果，即 FOURIER-OLE 研究，旨在評估 Repatha 在 6,600 多名患有臨床明顯動脈粥樣硬化的高危成人中的長期安全性和耐受性心血管疾病對穩定有效的他汀類藥物治療。

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 OLE 研究中，患者接受 Repatha 大約 5 年，在 FOURIER 和 OLE 研究中，一些患者接受 Repatha 的時間總計長達 8.5 年。這些研究的綜合結果加強了 Repatha 在降低 LDL 膽固醇方面的長期安全性和耐受性。我們對這種藥物對心血管疾病患者的持續益處感到非常鼓舞，這些患者仍然難以將低密度脂蛋白膽固醇水平降至推薦目標以下。

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.

這些針對 Repatha 患者的擴展結果與醫療保健界在過去 7 年中對降低膽固醇益處的了解是一致的。穩健且持續的 LDL 膽固醇降低會影響一系列重要的心血管結局。我們期待在今年晚些時候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，我們將繼續在我們的創新和生物仿製藥產品組合中快速執行，並期待在今年餘下的時間里分享來自我們多個項目的新數據。有了這個，我會把它轉回給 Bob 進行問答。

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，您能否提醒我們的來電者提交問題的流程？我們現在很高興回答問題。

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

（操作員說明）您的第一個問題來自 Jefferies 的 Michael Yee。

Can you hear me okay?

你能聽到我的聲音嗎？

Yes, Mike, go ahead.

是的，邁克，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。戴夫的問題。顯然，KRAS 領域的競爭非常激烈，您有一個非常重要的 III 期 LUMAKRAS 驗證性研究正在宣讀。我只是想知道你對多西紫杉醇獲得積極結果的期望的信心，你能以多快的速度提交文件，以及這是否會改變你周圍競爭對手加速批准的範式。所以也許只是評論那項研究及其後果。

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。如果我們複製我們迄今為止在 LUMAKRAS 上觀察到的情況，我認為，邁克，我們將對多西他賽的 III 期試驗很有信心，當然，多西他賽已經存在了幾十年，這將是積極的。當然，我們會與 FDA 和其他監管機構討論如何歸檔這些數據並獲得全面批准。至於對競爭格局的影響，我會留給其他人評論。但在這一點上，我們對 LUMAKRAS 非常有信心。我們在全球大約 40 個國家/地區獲得批准。該計劃進展得非常快，這是我們現在的重點。

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

您的下一個問題來自 Oppenheimer 的 Jay Olson。

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?

隨著您繼續為 Repatha 生成重要的新臨床數據，您將獲得 Olpasiran、AMG 133 的數據。我看到您最近發布了 AMG 986 治療心力衰竭的數據。看起來你正在建立一個越來越強大的心血管產品組合。您能談談您在心血管疾病方面的策略嗎？那裡有哪些巨大的機會？您的心血管產品組合中是否存在您可能想要尋求業務發展機會的空白？

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.

我為什麼不拿最後一塊呢？戴夫，你為什麼不回應第一個？我會開始的。我認為 Murdo 也想發表評論，可以加入。謝謝，傑。我認為你提出了一個非常重要的問題。眾所周知，心血管疾病是我們研究的三個主要治療領域之一。它仍然是我們前進的重點領域。就全球發病率和死亡率而言，它仍然是排名第一的公共衛生負擔。這在一定程度上激發了我們對 Repatha 的承諾。 Murdo 將在一分鐘內發表評論，但我們相信有巨大的機會為患者提供一個可能在 LDL 膽固醇方面在醫學上得到最好證明的假設。

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) 計劃、Olpasiran 或 AMG 890。提醒大家，就動脈粥樣硬化性心血管疾病的發病機製而言，Lp(a) 可能是除 LDL 膽固醇之外最重要的單一驅動因素。正如我所指出的，我們期待在接下來的幾個月中，這些項目中的 IIb 期數據。如果這些數據複製了我們在第一階段看到的數據，我們的目標是盡快過渡到第三階段。此外，我認為，我們有一個非常活躍的臨床前研究組合，這表明我們對該領域的持續戰略承諾。

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

Murdo，也許我接下來會轉給你，然後 Bob 可以談談業務發展。

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，心血管疾病巨大的未滿足醫療需求的基礎是我們有能力接觸到全球患者群體，我們已經建立了醫療和商業能力以及全球足跡來支持該業務。我們報告 Repatha 的銷量增長 49%，銷售額同比增長 15%。所以我們現在顯然有動力，我們繼續覺得我們還有更多的事情要做。

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.

我們也非常清楚，我們專注於提高這些患者的藥物負擔能力。我認為這是我們取得巨大進步的另一個領域。因此，通過我們自己的內部管道添加到該產品組合中是一件受歡迎的事情。而且我認為 Dave 的團隊正在非常努力地工作，不僅是在管道資產上，而且還在通過正在進行的 VESALIUS 試驗來改善 Repatha 的形象。當然，最近宣布的長期隨訪試驗仍在繼續。因此，安進在心血管疾病中的地位很強。我將把它交給鮑勃關於業務發展的問題。

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。在那裡，這很簡單，傑伊。我們要求我們的業務開發和研究團隊在外部尋找有吸引力的創新，並將其添加到我們的產品組合中。因此，我們正在尋找可以每天為心血管疾病、炎症疾病和癌症增加價值的東西。

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

您的下一個問題來自美國銀行的 Geoff Meacham。

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，與你去年第一次談論它時相比，在這次財報電話會議上與美國國稅局的稅務糾紛的評論要多得多，我認為可能會有更多的投資者預期。所以問題是，最近是否與該機構或服務機構進行了討論，從而促成了今天更廣泛的語言？而且我知道這需要數年時間才能完全解決，但您是否希望您的稅收儲備在討論過程中發生變化？或者這只是一個停滯不前的數字？然後當你完全解決它時，你會適當地做出改變嗎？

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，謝謝你的問題。看，我們不會 - 我們正在訴訟中，所以我們不會先評論與 IRS 的討論。其次，關於儲備，正如你所理解的，我們不會就儲備規模發表評論，只是說我們對自己的立場和水平非常有信心我們建立的儲備。正如我們所說，這是關於波多黎各以及美國和美國波多黎各領土之間的利潤分配，我們在波多黎各進行了大部分的全球製造。波多黎各是我們旗艦製造綜合體的所在地，擁有 30 年的經營歷史，擁有 2,400 - 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價值。我們將對 2010 年至 2015 年提出的調整提出激烈的異議。

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

您的下一個問題來自高盛的 Salveen Richter。

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?

在 LUMAKRAS 上，您可以採取哪些步驟來確保 G12C 狀態得到醫生的認可，以便在這裡開具處方？您是否還可以為夏末公佈的 KEYTRUDA 組合研究制定前景？

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，薩爾文。也許我會開始，然後將數據問題交給戴夫。顯然，我們正在與所有腫瘤學提供者密切合作，以改善他們自己的內部系統，從而使他們擁有 KRAS G12C 狀態，幾乎可以為他們的患者做出治療選擇。我們看到的是一點點 COVID 宿醉效應。美國的許多大型腫瘤學網絡人手不足，而且資源有限，他們可以針對 EMR 增強等事物部署資源，針對診斷和生物標誌物（尤其是新生物標誌物）的更好工作流程等。

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.

因此，我們在全國范圍內逐個帳戶地工作。我們已經做出了巨大的改進。我們已經看到了一些非常大的社區腫瘤學網絡，80% 的患者都在這裡接受治療。他們在社區中心接受治療。我認為在學術機構中，測試非常強大、穩健。護理是明確的，檢測結果可用於進展的患者。所以這真的是在我們工作的美國社區環境中。

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?

當我們從美國看時，我們看到了不同國家的不同模式。因此，像德國和法國這樣擁有先進生物標誌物技術和非常清晰系統的國家，我們預計那裡會有很好的吸收，我們已經看到了早期跡象。您可能還記得，法國有一個稱為 ATU 計劃的早期訪問計劃，我們可以在該計劃中實際對產品收費，並且已經相當廣泛地使用該計劃。在德國，我們剛剛推出幾週，就像我們在日本一樣。因此，我認為這是一個逐個網絡的項目，我們正在與我們的醫療同事、我們的商業團隊密切合作，以確保沒有患者漏診。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。正如我們所指出的，就數據可用性而言，我們已經為其中一場夏季腫瘤學會議提交了數據。我們正在研究 PD-1 抑製劑的組合和順序方法。我還要指出，我們開始檢查的一件事是所有非小細胞肺癌患者。您可以將它們大致分為 1/3 是 PD-L1 陰性腫瘤； 1/3 具有低到中等的 PD-L1 表達；和 1/3 具有高 PD-L1 表達。例如，在 PD-L1 陰性人群中，檢查點抑製劑的效果相當溫和，這是我們正在研究 LUMAKRAS 與直接化療組合的領域。因此，隨著該領域的發展，需要記住的一件事是，根據 PD-L1 的表達，臨床上的方法也可能會有所不同。我們正在相應地制定我們的發展計劃。

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

您的下一個問題來自摩根士丹利的 Matthew Harrison。

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?

偉大的。我希望能向默多提問。 Murdo，您能否發表評論-我知道您在商業評論中評論了您對合同特別是生物仿製藥合同的想法，因為我們考慮了 HUMIRA 的推出和其他一些產品。關於進展情況或您對 2023 年和 2024 年特別是 HUMIRA 的期望是否有任何更新的想法？

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，馬修，這個問題。不，我真的沒有很多新信息可以更新你。截至 1 月 31 日，我們仍然覺得我們處於非常有利的位置，有機會在 2023 年的一段時間內成為第一個，如果不是第一個，也可能是唯一一個生物仿製藥。

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.

我們喜歡我們的形象，因為我們——你會記得，我們使用現有的炎症商業組織，該組織目前將 Enbrel 和 Otezla 商業化，與風濕病學家和皮膚科醫生有完整的關係。實際上，我們也有一個 GI 足跡，也支持我們獨自一人。所以我們覺得我們已經建立了客戶關係。我們肯定有付款人關係。顯然，我們擁有 40 年的生物製劑製造和每次供應每位患者的經驗，為藥房福利管理人員提供信心，讓他們有信心做出讓我們的產品儘早上市的決定。

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興奮。然後，當然，在美國推出 AMGEVITA 之後，我們還推出了其他幾個產品，STELARA、EYLEA、Soliris，然後是其他產品。因此，有 6 種新的生物仿製藥進入市場。所以這是我們非常關注的一個領域。我們在這個領域進行了投資。這對我們的長期增長很重要，我們有能力在市場上確保成功。

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

您的下一個問題來自 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?

偉大的。我想，彼得，也許是為了你和團隊的其他人。我想，彼得，對你來說，首先，今年的稅率是遞增的。這與美國國稅局正在進行的訴訟有關嗎？還是因為不同的原因？

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.?

然後也許，默多，為你。在美國，LUMAKRAS 正在增長，但增長速度可能比我們預期的要慢一些。您是否期望前美國比美國更大或規模相似？

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。讓我先跳到這裡。我認為默多不想承擔稅收的一部分。所以看，我們只是將其上調了 50 個基點，Yaron。這和稅務訴訟完全沒有關係。也許這突出了我應該早一點回答 Geoff 的 [好] 問題的觀點，這就是為什麼現在要更多評論的原因。我認為這正是原因所在，因為對於你們所有人，對於分析師來說，這都是一個複雜的領域。我們希望確保您了解我們的立場。我們認為，根據之前的電話會議，人們很難理解。所以我們只想更具體一點。

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.

但就該問題本身而言，它根本不相關。再次，Yaron，謝謝你的提問。我們對我們的地位和我們所處的儲備水平充滿信心。但我們想為您提供更多的背景知識。所以希望這會有所幫助。現在我將把它交給 Murdo 讓他重新開始工作。

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，彼得。 Yaron，我想說的是，在美國，我們在 LUMAKRAS 上看到的是，當 KRAS G12C 狀態在從一線治療進展到二線治療時已知時，我們讓超過 80% 的患者成為由 LUMAKRAS 治療。因此，當確定 KRAS G12C 狀態時，我們正在滲透人群。所以這顯然是我們需要確保改進的槓桿。正如我之前回答 Salveen 的問題一樣，這確實是一本逐賬的工作簿。我們正在緊急這樣做，因為我們真的不能讓患者從一線進入二線，也不能選擇 LUMAKRAS。所以這是我們為患者所做的非常重要的工作。

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.

當我們比較美國與美國以外的疾病流行病學時，我會說美國和歐洲的非小細胞肺癌的總體發病率在規模上是相似的。現在，當您進入亞洲時要考慮一件事，因為 KRAS G12C 突變狀態的發生率要低一些。如果以日本為例，大約 4% 的非小細胞肺癌患者也有 KRAS G12C 突變，而在美國這一比例為 13%。因此，當您離開美國時，突變流行病學確實會發生一些變化。和歐洲。因此，我們預計美國的業務將略大於歐洲和世界其他地區的業務。

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

您的下一個問題來自 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?

我猜兩個，如果可以的話。首先，也許在 KRAS 上。幻燈片上有一個有趣的披露，關於 2,500 名患者如何在美國商業上服用它。第三方數據集表明，3 月份可能有 1,200 名患者服用了這種藥物。我正在嘗試將這兩個平方。 3 月份約有 1,200 名患者接受治療，總接觸量為 2,500 名。粗略的數學表明，治療的持續時間已經跟踪了 5 個月左右。這與你的觀察一致嗎？

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，彼得，在稅務法庭方面，你能指導我們了解時間線的樣子嗎？因為我覺得這是這些主題之一。現在有兩套責任，人們會以某種方式以某種概率將它們放入他們的模型中，並了解解決問題的時間線，或者至少，關於聽證會何時或何時是關鍵稅務法庭的開庭日期即將到來，這將非常有幫助。

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。也許是關於患者人數和治療持續時間的第一個問題。我認為現在能夠從藥物數字與接受 DOT 或治療持續時間的治療數字得出結論還為時過早。我想，你需要了解的是，在 2,500 名患者中，我們有很多處於晚期疾病、三線及以上潛在疾病的患者，他們受到產品的挑戰並且表現不佳。而穩定狀態將是更多的二線患者可能已經經歷過一種先前的治療，他們可以做得很好，正如我們剛剛在 AACR 上發布的長期隨訪數據所表明的那樣，你看到大約 1/3的患者在 2 年隨訪時還活著。

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.

因此，我認為從現有的市場上患者數量推斷來了解治療的有效持續時間還為時過早。事實上，我經常說這是你真的需要 24 個月的市場才能了解你的回顧期是什麼，了解你的治療持續時間是多少。因此，要知道我們在現實世界中的治療持續時間是多少，還需要相當長的一段時間。

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.

烏默爾，彼得在這裡。所以在稅收方面，謝謝。就下一步和時間表而言，我們將在 90 天內向美國稅務法院提交請願書。正如我所提到的，我們將通過司法程序對 2013 年至 2015 年的通知進行激烈的競爭。我們計劃將 2013-2015 年期間與正在進行的 2010 年至 2012 年稅務法庭案件合併。正如我所說，這需要幾年時間才能自行解決。這就是我們所看到的當前時間框架。

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

您的下一個問題來自 Barclays 的 Carter Gould。

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.

也許可以專注於 TEZSPIRE。我希望在那裡獲得更多色彩，特別是您如何看待那裡的 J 代碼的重要性以及可能推動銷售拐點的程度，我想這是迄今為止的障礙。然後很明顯，你最近開始了 WAYFINDER。過去，你們有點輕描淡寫 SOURCE 結果的重要性。因此，當我們考慮 WAYFINDER 時，這對於解決這一差距是否至關重要，或者僅僅是一個很好的選擇？那裡的一些顏色會很有幫助。

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，我們對市場對 TEZSPIRE 的反應感到非常興奮，因為它擁有如此新穎、獨特的產品，該產品的配置文件真正簡化了嚴重不受控制的哮喘的治療，特別是對於有很多其他工作要做的肺科醫生來說。正在尋找一種簡單的解決方案，可以治療他們的患者而不受表型或生物標誌物狀態的限制。所以總的來說，我們認為進展非常順利。

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.

在市場上擁有一個永久的 J 代碼顯然是一個好處，正如我所提到的，這將在 7 月 1 日推出。這讓供應商和他們的計費人員相信他們可以適當地對產品進行編碼並具有高度的報銷保證。我認為他們知道現在正在報銷，但現在也是對其中一些做法進行報銷的時候了。他們中的一些人的現金流非常緊張。並且知道永久 J 代碼應該加快報銷時間實際上會有所幫助。所以是的，我會說這會很有幫助。

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.

但我想說的是，目前的市場反應非常好。我們顯然正在為正在經歷該過程中報銷步驟的患者提供產品，以便他們能夠接受治療並獲得藥物。但是，是的，我們正在尋找額外的銷售隊伍——今年下半年的銷售增長。

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 而言，我們相信這項試驗將解決一些方法學限制，我們相信我們在 SOURCE 試驗中看到了這一點。樣本量要大得多。這是一項單臂試驗，樣本量超過 300 名患者。患者可以服用更高劑量的類固醇。可以有更快速的皮質類固醇減量。我們正在更早的時間點更早地研究效果。我認為，所有這些都讓我們有信心看到 TEZSPIRE 在降低口服皮質類固醇使用方面的有效性。

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 會議上展示了 NAVIGATOR 和其他試驗的更新數據，顯示口服皮質類固醇患者的急性加重顯著減少。同樣，我認為這將成為治療各種表型哮喘的非常重要的藥物，我們對未來的開發計劃充滿信心。

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?

所以只有一對夫婦在 Repatha。因此，請談談您對 inclisiran 的看法以及 7 月份推出的永久 J 代碼以及您對下半年對 Repatha 的影響的看法。然後就在第二個，您在 Repatha 方面取得了令人矚目的增長。也許你可以給醫生的劇本趨勢多一點色彩。您是否看到更多心髒病專家的腳本？有哪些趨勢讓你相信，這種增長可以持續到開藥方，而我認為，在早期，主要是脂質學家？

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，羅賓。我們對 Repatha 的發展感到滿意。整個心髒病學界的增長實際上是相當一致的。因此，不僅僅是您的脂質專家，還有各種心髒病專家。我們正在看普通的社區心髒病專家。我們還在綜合交付網絡和醫院系統上投入了大量精力，我們成功地建立了一種更標準化的方法來治療美國約 2500 萬高危 ASCVD 患者，這些患者最終在急性護理機構接受 MI或其他他們被錄取的事件。

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，他們中的許多人甚至沒有得到血脂檢查，其中許多人在沒有適當建議或開始治療的情況下就出院了。因此，我們已經大大提高了這一點，並且我們看到了護理質量的提高。這些患者隨後將出院到社區心髒病專家和/或初級保健醫生那裡，他們更明確地打算進行更積極的降脂治療或降低心血管風險。所以這絕對是有幫助的。

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.

對於未來的增長，我們顯然將繼續努力，我們將繼續擴大我們將在美國開展的 IDN 工作。但鑑於此，我們還將逐步投資於初級保健我們看到一些自發的初級保健處方。因此，我們對 Repatha 的成長感到非常滿意。

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.

在美國，我要提到的另一件事是，我們在 1 月 1 日將 Repatha 列入中國國家報銷藥物清單，這對我們來說是一個很好的發布。我們在中國的團隊在確保 Repatha 成為該國高危 ASCVD 患者的選擇方面做得很好。所以真的，我認為我們在這個產品上有很大的增長空間。患者人數眾多，我們現在在心髒病學方面發展勢頭良好，我們需要繼續將其納入初級保健和世界各地。

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.

關於 inclisiran，顯然，他們是市場上的競爭對手。但鑑於他們還沒有事件減少數據，即使有報銷編碼，我認為他們仍然可以推廣的內容有限。但同樣，有大量患者需要更積極的降脂治療和更積極的心血管風險降低，我們看到市場可以承受很多人談論這種嚴重的疾病，世界上的第一殺手每個關心病人的人以及我們能做些什麼。所以總的來說，我們仍然非常看好。

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，我知道我們有幾個來電者仍然希望提出問題。我只是想提醒來電者，我們可能會在一小時後幾分鐘。那麼，我們為什麼不回答下一個問題，我們會盡最大努力解決每個人的問題。如果我們無法做到這一點，那麼我們將 - 顯然，Arvind 和他的團隊將在稍後提供。

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

您的下一個問題來自富國銀行的 Mohit Bansal。

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?

也許是關於 TEZSPIRE 的問題。因此，考慮到現在，它需要由提供者管理，你是否 - 鑑於 Dupi 可用於自我管理，你在這一點上期望醫生在開出代理方面有什麼樣的保留？問題是，未來是否有可能想出一種自我給藥的注射劑，實際上可以幫助它成為一種自我給藥的家用產品？

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。 - 不幸的是，因為嚴重的哮喘，尤其是不受控制的嚴重哮喘，是一種如此急性的疾病，這些患者中的許多人經常接受肺科醫生或過敏症專家的護理。所以他們會定期去看醫生。而且我認為鑑於我們非常方便的每月一次給藥，它被視為一種相當容易管理的產品。當然，現在還處於發布的早期階段，但反饋是醫生管理不是啟動 TEZSPIRE 的障礙。尤其是過敏症患者，他們習慣於使用醫生管理的產品。

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.

我認為真正發揮出來的好處是他們在生物標誌物方面或表型評估方面要做的工作要少得多。因此，我們在這方面簡化了他們的工作流程。我確實認為，從長遠來看，我們將繼續評估我們需要做些什麼來確保為患者提供便利和維護。顯然，我們正在尋找 TEZSPIRE 的其他跡象和其他生命週期機會。因此，我們將繼續評估是否要提供自我管理的選項。我的意思是，很明顯，產品可以以這種方式開發，我們將繼續關注這一點。

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

您的下一個問題來自 Raymond James 的 Dane Leone。

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?

祝賀本季度。給我一個問題。假設 LUMAKRAS 的劑量等效性研究實際上表明 240 毫克 Q 日相當於 960，那麼您計劃如何在年底管理這種轉變？我們從投資者那裡得到這個問題的原因很明顯，這將與 KRAS G12C 領域的競爭對手的假定推出相吻合。也許僅僅從給出的腳本來框架它，在年底給出一個 30 天的腳本，如果這個劑量當量確實表明較低的劑量是等效的，那麼 30 天的腳本變成一個 120 天的腳本.您的團隊是如何考慮管理這個問題的？如果較低劑量被視為等效，定價是否會發生預期變化？

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，這是一個非常詳細的假設。我想說的是，首先，我們仍然相信 960 毫克的劑量是正確的劑量。顯然，該產品的安全性和有效性益處看起來非常好。鑑於長期的隨訪數據，很明顯，我們能夠看到它是否可以以較低的劑量獲得批准是一個很高的標準。所以這是一個有待回答的問題。

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.

順便說一句，我想 - 我不能直接回答你的問題，因為它有很多不同的複雜變量。但我想說的是，我們將繼續尋找為持續患者提供正確治療的最佳方法。因此，如果您是二線非小細胞肺癌患者，您已在 960 處接受了 LUMAKRAS 處方，您正在服用，您已經做出反應並且病情穩定，我不確定是否有任何腫瘤學家如果你是一個持續的病人，你會想要降低你的劑量。現在我們已經看到，在其他可能發生劑量變化或上升或下降的疾病領域，服用穩定劑量的患者通常會繼續服用。所以這將是我對你的問題的一點補充評論。但是我們會等待，我們會看到數據，我們會根據數據所說的以及 FDA 指導我們做的事情來處理它。

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

您的下一個問題來自 BMO Capital Markets 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.

我想問一個來自 Murdo on Otezla 的問題，因為截至去年 12 月，我們已經獲得了完整的標籤或全頻譜批准。那麼，你有沒有看到針對較輕症患者的任何障礙？這些患者是否需要進行任何形式的步驟編輯，或者他們是否能夠非常自由地獲得它？您預計這一情況會在一年中發生變化嗎？只是喜歡了解您如何在這些患者中推廣或營銷它。

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.

謝謝你的問題，埃文。不，我們對付款人和 PBM 的反應感到非常滿意，以確保現在擴大標籤，無論銀屑病的嚴重程度如何，患者都可以擁有強大的訪問權和良好的產品負擔能力。事實上，與去年相比，我們實際上已經改進了今年的訪問。因此，我們已經能夠制定一些事先授權標準，例如體表面積百分比。有一些醫療政策，事先授權被描述為百分比。我們已經刪除了許多。因此，我們實際上已經為這些患者開放了訪問權限。而且我認為 [更容易] 為那個較輕的患者開 Otezla。

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.

我在三月份的美國皮膚病學會會議上與許多皮膚科醫生交談，詢問他們的處方經驗和報銷經驗是什麼。而且我認為他們中的許多人向我們反映，Otezla 比過去更容易為那個溫和的患者開藥。我們做的另一件事是我們加強了我們的共同支付援助和我們自己的過渡計劃，以確保發射順利進行。到目前為止，一切都很好。一個好的開始，但我預計訪問不會成為障礙。

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，考慮到東海岸的人們，已經過了一個小時。那我們為什麼不多問兩個問題呢？

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

您的下一個問題來自摩根大通的 Cory Kasimov。

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?

這是科里的加文。我剛剛在夏末對 LUMAKRAS-pembro 組合數據隊列中的一個問題進行了後續跟進。我猜只是肺癌患者，你能提醒我們這是否主要是二線加法嗎？或者前線是否有足夠的患者來評估路徑或前進的路徑？

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.

然後我們是否也應該尋找多劑量和/或不同的給藥方式？我想你在過去討論過順序給藥與其他策略。

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。這些患者中的大多數將是二線及以上。也許一線治療的經驗有限，我們正在研究聯合治療和序貫治療的一系列劑量。因此，當數據出現時，您可以期望看到所有這些。

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

讓我們回答最後一個問題，RJ。在那之後，Bob 將發表一些結論性意見。

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

您的下一個問題來自瑞銀的 Colin Bristow。

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?

我會保持這個快速。只是很快就稅收問題。您能否談談我們是否應該將其視為基本上僅限於 2015 年？或者這是否真的可以有效滲透到 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.

然後很快就在 LUMAKRAS 上。幾週前在 ELCC 上展示了一個由研究人員主導的小型數據集。我們看到一些相對較高的 LFT 升高率，LUMAKRAS 劑量與 PD-1 密切相關。我只是好奇這與您自己的組合與順序給藥經驗相比如何。以及關於那裡的前進道路你可以說的任何其他內容。

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。看，在這個案子上，我們對我們的職位和我們的結構以及我們如何在波多黎各和美國之間分配利潤非常有信心。所以我們對這些儲備非常有信心。如果您確實考慮過向前發展，我確實在新聞稿中建議說 IRS 目前正在審計 2016 年至 18 年。如果他們確實提出了任何轉讓定價（聽不清），那麼這些調整的幅度將因 2017 年稅法的稅率變化而減少，這會將美國和波多黎各適用的稅率之間的差異減少大約 2/ 3 從 2018 年開始。但再一次，我們對我們的結構（聽不清）非常有信心，我們對儲備水平非常有信心。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，你想抓住第二塊嗎？

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 數據，這些是來自法國一位研究人員的不受控制的數據，患者可能在檢查點抑製劑後接受單藥治療。我可以告訴你，肝毒性的發生率高於我們在臨床試驗計劃中和通過我們正在進行的藥物警戒工作所觀察到的。所以我不確定為什麼會這樣，但這是一組異質的未經選擇的患者。我們很難對這些數據做出進一步評論。

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.

讓我感謝大家撥入。我們感謝您的支持和對公司的興趣。正如我們試圖通過這個電話傳達的那樣，我們覺得我們在 2022 日曆年的表現很好。我們期待在第二季度之後與您重聚，報告我們在年中取得的進展。謝謝你。抱歉，我們過了幾分鐘。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，我們感謝大家的參與。您現在可以斷開連接。