美國安進 (AMGN) 2021 Q1 法說會逐字稿

My name is Erica, and I will be your conference facilitator today for Amgen's First Quarter 2021 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 Erica，今天將擔任安進公司 2021 財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。

Erica, thank you. Good afternoon, everybody. Welcome to our Q1 call. I think the 2 key themes for this quarter, our continued focus on volume-driven growth and pipeline advancement. Lots to cover, but we'll do our best to stick to an efficient format of limited prepared comments and addressing your one best question. The slides have been posted. Just a quick reminder that we'll use non-GAAP financial measures in our presentation and some of the statements will be forward-looking statements. Our SEC filings identify factors that could cause our actual results to differ materially.

艾麗卡，謝謝。大家下午好。歡迎參加我們的第一季電話會議。我認為本季的兩個關鍵主題是：我們將繼續專注於以銷售驅動的成長和推進產品線。內容很多，但我們會盡量採用高效率的流程，只做有限的準備發言，並回答大家最關心的一個問題。幻燈片已經上傳。再次提醒大家，我們的簡報將使用非GAAP財務指標，部分陳述屬於前瞻性陳述。我們提交給美國證券交易委員會（SEC）的文件列出了可能導致實際業績與預期有重大差異的因素。

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. We've had a busy start to 2021 and a first quarter that's something of a mere image to what we experienced a year ago. Last year, if you recall, we came out of the gate with a very strong January and February and then started to really feel the impact of the pandemic in March. This year, especially in the U.S., it was almost the reverse. We felt the impact of the pandemic in January and February, and we began to see a recovery in March, a trend that seems to be holding in April as well.

好的。謝謝Arvind，大家好，謝謝各位參加我們的電話會議。 2021年伊始我們就非常忙碌，第一季的情況與去年同期相比簡直是天壤之別。大家可能還記得，去年一月和二月我們開局非常強勁，但到了三月就開始感受到疫情的影響。而今年，尤其是在美國，情況幾乎正好相反。我們在一月和二月感受到了疫情的影響，三月開始出現復甦跡象，而且這種趨勢似乎在​​四月也仍在持續。

Setting aside the pandemic, we executed effectively in the first quarter. And this is reflected in the strong competitive performance of our brands globally, our strong biosimilars showing, the rapid progress of our lead pipeline molecules and the addition of an attractive Phase III-ready molecule in oncology. Altogether, we remain confident in our full year outlook.

撇開疫情影響不談，我們在第一季的營運卓有成效。這體現在我們旗下品牌在全球範圍內的強勁競爭表現、生物相似藥的優異業績、主導研發管線分子的快速進展，以及新增的一款極具吸引力的腫瘤學III期臨床試驗候選藥物。總而言之，我們對全年前景充滿信心。

We're fortunate to have a diverse portfolio of newer products that continue to show strong volume growth. Repatha, for example, delivered 36% volume growth in the first quarter. It remains the clear leader of the PCSK9 market globally and will soon reach the milestone of 1 million patients served.

我們很幸運擁有多元化的新產品組合，這些產品持續保持強勁的銷售成長。例如，Repatha 在第一季實現了 36% 的銷售成長。它仍然是全球 PCSK9 市場的絕對領導者，並將很快達到服務 100 萬名患者的里程碑。

We're also the global leader in bone health with Prolia and EVENITY, generating double-digit volume in the quarter. Our industry-leading portfolio of biosimilars is annualizing above the $2 billion mark, and I would remind you that we have 3 additional biosimilars in Phase III development and look forward to a flow of new launch opportunities for these and AMGEVITA over the next few years.

我們在骨骼健康領域也處於全球領先地位，旗下產品Prolia和EVENITY在本季實現了兩位數的銷售成長。我們產業領先的生物相似藥產品組合年銷售額已超過20億美元。此外，我們還有3款生物相似藥處於III期臨床試驗階段，並期待在未來幾年內，這些產品以及AMGEVITA能夠迎來一系列新的上市機會。

As we've shared with you many times in the past, we're active in business development, looking to complement our internally developed innovation with compelling external opportunities, and our recent acquisition of Five Prime Therapeutics is a good example of that.

正如我們過去多次與您分享的那樣，我們積極開展業務拓展，尋求用引人注目的外部機會來補充我們內部開發的創新，而我們最近收購 Five Prime Therapeutics 就是一個很好的例子。

As you know, one of the molecules we acquired in that deal, bemarituzumab, was granted breakthrough therapy designation by the FDA as a first-line therapy for a subset of patients with gastric cancer. More than 1 million new gastric cancer cases are diagnosed annually, and the disease is particularly prevalent in the Asia Pacific region, which we've said previously will account for approximately 25% of our growth over the next decade. Bemarituzumab is now our third late-stage clinical medicine to be granted breakthrough therapy status joining sotorasib for which the trade name LUMAKRAS has now been provisionally approved for use in the U.S. And tezepelumab also has earned that breakthrough therapy distinction.

如您所知，我們在那筆交易中收購的分子之一，貝馬裡單抗（bemarituzumab），已被美國食品藥物管理局（FDA）授予突破性療法認定，用於治療部分胃癌患者的一線治療。每年新增胃癌病例超過100萬例，該疾病在亞太地區尤為普遍，我們先前曾表示，未來十年該地區將占我們成長的約25%。貝馬裡單抗是我們第三款獲得突破性療法認定的後期臨床藥物，此前，索托拉西布（sotorasib，商品名為LUMAKRAS）已獲得美國臨時批准上市。此外，特澤佩魯單抗（tezepelumab）也獲得了突破性療法認定。

With a strong balance sheet, healthy cash flows and our proven ability to integrate, we'll continue to look for external opportunities that strengthen us in our stated areas of focus.

憑藉強勁的資產負債表、健康的現金流以及我們已被證明的整合能力，我們將繼續尋找外部機會，以加強我們在既定重點領域的實力。

Before I turn things over to our CFO, Peter Griffith, I want to thank my Amgen colleagues for their continued commitment to serving patients around the world and delivering results for our stakeholders. I look forward to our Q&A session a little later in our call. But for now, over to you, Peter.

在將發言權交給財務長彼得·格里菲斯之前，我要感謝安進的同事們，感謝他們一直以來致力於服務全球患者，並為我們的利益相關者創造佳績。我期待稍後在電話會議上的問答環節。現在，請彼得發言。

Thank you, Bob. I would like to take a few moments to reflect on the strong fundamentals of the business and further to reaffirm our full year revenue and non-GAAP EPS guidance.

謝謝你，鮑伯。我想花幾分鐘時間回顧一下公司穩健的基本面，並再次重申我們全年營收和非GAAP每股盈餘預期。

Let me first confirm our predictable consistent capital allocation hierarchy as seen in our Q1 activity. It always begins with investing in internal innovation. LUMAKRAS and tezepelumab, both internally discovered and each branded breakthrough therapy designation, are excellent examples of this. We also patiently pursue external business development opportunities that clear our hurdle rate and that are consistent with our areas of therapeutic focus in which we are confident of integrating into Amgen efficiently and effectively on a timely basis. We allocated $2 billion of our shareholders' capital to the Five Prime acquisition in the second quarter and have committed additional R&D funding to pursue other indications for the lead molecule bema.

首先，我想重申我們一貫的資本配置層級，正如我們在第一季的業績中所體現的那樣。這始終始於對內部創新的投資。 LUMAKRAS 和 tezepelumab 都是我們內部研發的，並且都獲得了突破性療法認定，它們就是很好的例子。同時，我們也耐心尋求外部業務拓展機會，只要這些機會能夠達到我們的最低投資回報率，並且與我們重點關注的治療領域相符，我們都有信心能夠高效、及時地將其整合到安進的業務中。第二季度，我們向 Five Prime 收購案投入了 20 億美元的股東資金，並已承諾追加研發資金，用於探索其主要候選藥物 bema 的其他適應症。

Our capital expenditures remain a high priority, including investments in our industry-leading protein manufacturing, our ESG initiatives, including enabling carbon neutrality by 2027 and digitization imperatives. We continue to return capital to our shareholders. First, we paid dividends of $1.76 per share in the quarter, representing a 10% increase from 2020. This year marks our 11th year of dividends with meaningful increases in each of those years. Second, we repurchased 3.7 million shares in the first quarter at a cost of roughly $865 million. Finally, our capital allocation hierarchy always builds on our efficient capital structure, which results in an optimal weighted average cost of capital.

我們的資本支出仍然是重中之重，包括對我們行業領先的蛋白質生產、ESG（環境、社會和治理）舉措（包括實現2027年碳中和）以及數位轉型等方面的投資。我們持續向股東返還資本。首先，本季我們派發了每股1.76美元的股息，較2020年成長10%。今年是我們連續第11年派發股息，並且每年都實現了顯著成長。其次，我們在第一季回購了370萬股股票，耗資約8.65億美元。最後，我們的資本配置始終以高效率的資本結構為基礎，從而實現了最優的加權平均資本成本。

Now I will briefly walk through our first quarter financial results. Recall that in 2021, we are now comparing to our recast 2020 results that exclude the impact of fair value adjustments to equity investments that were historically included in non-GAAP OI&E. In Q1, revenues decreased 4%. Historically, first quarter sales have been the lowest quarter as a percentage of the full year. As we entered 2021, we knew that COVID would likely introduce some variability. And as the quarter progressed, and we saw a continuing cumulative effect of COVID cases on prescribing patterns, we anticipated that Q1 would be more negatively impacted, which led us to disclose in March that it would be moderately below 2020's percentage of the full year.

現在我將簡要回顧我們第一季的財務表現。需要注意的是，2021 年的業績是與我們重述後的 2020 年業績進行比較的，重述後的業績剔除了以往計入非 GAAP 經營損益表中的權益投資公允價值調整的影響。第一季度，收入下降了 4%。歷史上，第一季的銷售額佔全年銷售額的比例通常是最低的。進入 2021 年時，我們就知道新冠疫情可能會帶來一些波動。隨著季度的推進，我們看到新冠病例對處方模式的持續累積影響，因此我們預計第一季度受到的負面影響會更大，這也促使我們在 3 月份披露，第一季的銷售額佔全年銷售額的比例將略低於 2020 年同期水平。

First quarter sales benefited from 4% volume growth. Looking back to Q1 of 2020, we recorded approximately $150 million of favorable changes to estimated sales deduction, creating a negative impact on year-over-year growth comparisons in Q1 2021. As we get underway with the second quarter, we expect there to be some continuing cumulative COVID impacts. While we expect to see improvements in the rate of recovery, that recovery will be more heavily weighted to the second half of the year.

第一季銷售額受惠於4%的銷售成長。回顧2020年第一季度，我們錄得約1.5億美元的銷售預估扣除額的有利變動，這對2021年第一季的同比增速產生了負面影響。隨著第二季的開始，我們預計新冠疫情的累積影響將持續存在。雖然我們預計復甦速度會加快，但復甦的重點將更集中在下半年。

Total non-GAAP operating expenses for the quarter increased 2% year-over-year. For the full year, we continue to expect cost of sales as a percent of product sales to be 16% to 17%. Effective Q2 2021, cost of sales will increase as a percent of product sales in connection with our first shipments of antibody to Lilly. Recall that revenue from shipments of these antibodies will be recorded in other revenues. For the full year, we expect R&D spend will increase as our innovative pipeline continues to progress, which now includes bema from the Five Prime acquisition as well as the Rodeo acquisition. And for the full year, we expect SG&A spend to decline. We continue our focus on digitization imperatives.

本季非GAAP營運總支出較去年同期成長2%。我們預計全年銷售成本佔產品銷售額的比例仍為16%至17%。自2021年第二季度起，由於我們向禮來公司首次交付抗體，銷售成本佔產品銷售額的比例將會上升。請注意，這些抗體的交付收入將計入其他收入。我們預計全年研發支出將隨著我們創新產品線的持續推進而增加，該產品線目前包括收購Five Prime和Rodeo後獲得的bema。同時，我們預計全年銷售、管理及行政費用將有所下降。我們將繼續專注於數位轉型。

Non-GAAP OI&E was a net $375 million expense in Q1. This is unfavorable by $79 million on a year-over-year basis due to the recording of our portion of BeiGene's loss this quarter. Recall the recognition of BeiGene's results did not start until Q2 2020.

第一季非GAAP經營損益淨額為3.75億美元。由於本季計入了我們應承擔的百濟神州虧損，年比減少了7,900萬美元。需要注意的是，百濟神州的業績確認始於2020年第二季。

The effects year-over-year of the adjustments in sales deductions, combined with the recognition of the BeiGene results, totaled about $0.29 and decreased EPS on a comparison basis for Q1 '21 and explain a large portion of the 12% decline in EPS year-over-year.

銷售額扣除調整的影響，加上百濟神州業績的確認，同比總計約 0.29 美元，導致 2021 年第一季每股收益同比下降，並解釋了每股收益同比下降 12% 的主要原因。

Now turning to the outlook for the business for 2021. Based on underlying market dynamics and our investment plan, we are reaffirming our 2021 guidance with a revenue range of $25.8 billion to $26.6 billion and a non-GAAP EPS range of $16 to $17. Important additional points to consider as you model the remainder of 2021.

現在展望一下2021年的業務前景。基於基本的市場動態和我們的投資計劃，我們重申2021年的業績指引，預計營收為258億美元至266億美元，非GAAP每股收益為16美元至17美元。在2021年剩餘時間進行預測時，還需要考慮以下幾個重要因素。

We are providing more specific quarter-over-quarter guidance given the unprecedented continuing cumulative COVID impacts on the operating environment, but we do not expect to provide such guidance on an ongoing basis. We see the recovery from COVID-19 more heavily weighted to the second half of the year. And for the second quarter, we expect total revenues to grow between 7% and 10% sequentially from the first quarter. We continue to expect full year non-GAAP operating expenses to increase by about 7% over last year, with an operating margin of roughly 50%, which includes operating expenses for Five Prime and Rodeo.

鑑於新冠疫情對營運環境造成的持續累積性影響前所未有，我們提供更具體的季度環比業績指引，但我們預計不會持續提供此類指引。我們認為新冠疫情後的復甦將主要集中在下半年。對於第二季度，我們預計總營收將較上季成長7%至10%。我們仍預計全年非GAAP營運費用將比去年成長約7%，營運利潤率約為50%，其中包括Five Prime和Rodeo的營運費用。

Historically, the Q2 quarter-over-quarter operating expense increase is about 10%. But in the second quarter this year, we expect quarter-over-quarter operating expenses to increase in the mid-teens percentage range, reflecting the impact of our Lilly COVID-19 antibody manufacturing agreement, investments for growth, including the Five Prime acquisition as well as increasing activity levels, including launch preparations.

從歷史上看，第二季的營運費用較上季成長約為 10%。但今年第二季度，我們預計營運費用將環比成長將達到 15% 左右，這反映了我們與禮來公司簽訂的 COVID-19 抗體生產協議、成長投資（包括收購 Five Prime）以及不斷增加的業務活動水平（包括上市準備工作）的影響。

For the full year, we continue to anticipate non-GAAP OI&E to be a net expense in the range of $1.3 billion to $1.5 billion. Our capital expenditures guidance remains unchanged at $900 million. And based on our confidence in the long-range outlook of the business, we are raising the upper end of our share repurchase range to $5 billion for 2021 versus prior guidance of $4 billion. So our range for share repurchases in 2021 is now $3 billion to $5 billion. Additionally, we're updating our non-GAAP tax rate guidance to 13.5% to 14.5% versus prior guidance of 13% to 14%.

我們預計全年非GAAP經營損益淨支出仍為13億美元至15億美元。資本支出預期維持不變，仍為9億美元。基於對公司長期前景的信心，我們將2021年股票回購範圍上限從先前的40億美元上調至50億美元。因此，我們2021年的股票回購範圍現為30億美元至50億美元。此外，我們將非GAAP稅率預期從先前的13%至14%上調至13.5%至14.5%。

My confidence is strong in the long-term outlook for Amgen given the strength of the business and the strength of our outstanding and dedicated team of 23,000-plus colleagues that deliver every day to patients and also deliver long-term growth to our shareholders.

鑑於安進的業務實力以及我們超過 23,000 名傑出且敬業的同事組成的團隊每天為患者提供服務，同時也為我們的股東帶來長期增長，我對安進的長期前景充滿信心。

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

財務更新到此結束。接下來交給默多。默多？

Thanks, Peter. First quarter product sales declined 5% year-over-year. Volumes grew 4% driven by double-digit growth for a number of products, including Prolia, Repatha, MVASI and KANJINTI. Net selling price declined 7%, and the year-over-year comparison was negatively affected by 2% due to a benefit in Q1 2020 from approximately $150 million of changes to estimated sales deductions that did not reoccur to the same magnitude in Q1 of 2021.

謝謝，彼得。第一季產品銷售額較去年同期下降5%。銷售成長4%，主要得益於包括Prolia、Repatha、MVASI和KANJINTI在內的多款產品實現了兩位數成長。淨售價下降7%，年減2%，原因是2020年第一季受益於約1.5億美元的銷售預估扣減調整，而2021年第一季並未出現同等規模的調整。

In the first quarter, the cumulative effect of the COVID pandemic on missed patient visits and diagnoses impacted our business. January and February were clearly affected by post-holiday COVID spikes, and March showed demand improvement across most brands, which has continued into April. Despite the impact of the pandemic, our teams have found solutions to address the continuity of care, stabilizing our continuing patient volume. We also saw improvement in customer-facing execution throughout the quarter across all communication channels, including face-to-face and virtual activities. We expect some COVID-19-related disruptions still in the second quarter with steady recovery thereafter.

第一季度，新冠疫情對病患就診和診斷造成的累積影響波及了我們的業務。 1月和2月明顯受到節後疫情高峰的影響，3月多數品牌的需求已回升，趨勢延續至4月。儘管受到疫情的影響，我們的團隊已找到解決方案，確保醫療服務的連續性，並穩定了持續的患者數量。此外，本季所有溝通管道（包括面對面和線上活動）的客戶互動執行力均有所提升。我們預計第二季仍會受到一些與新冠疫情相關的干擾，但之後將穩定復甦。

I'll now review some product details, beginning with our innovative portfolio. In bone health, Prolia grew 16% year-over-year, recording over $500 million of U.S. sales in the U.S. for the first time. As a majority of osteoporosis patients in the U.S. have been vaccinated and diagnosis rates are at approximately 90% to pre-COVID-19 levels, we're confident in Prolia's continued growth in 2021. EVENITY sales increased 7% year-over-year driven by strong volume growth. Given the severe impact of fractures on the lives of postmenopausal women, EVENITY provides an excellent therapy to build bone first, which should then be followed by treatment with Prolia.

接下來，我將詳細介紹一些產品，首先介紹我們創新的產品組合。在骨骼健康領域，Prolia 年增 16%，在美國的銷售額首次突破 5 億美元。由於美國大多數骨質疏鬆症患者已接種疫苗，且診斷率已恢復到新冠疫情前水準的約 90%，我們對 Prolia 在 2021 年的持續成長充滿信心。 EVENITY 的銷售額年增 7%，主要得益於銷售量的強勁成長。考慮到骨折對停經後女性生活造成的嚴重影響，EVENITY 提供了一種卓越的骨骼重建療法，之後應配合使用 Prolia 進行治療。

Repatha sales increased 25% year-over-year to a quarterly sales record of $286 million driven by 36% volume growth, and we maintain global leadership in the PCSK9 class. Sales outside the U.S. grew by 40% driven by strong patient demand.

瑞百安（Repatha）銷售額年增25%，達到創紀錄的2.86億美元，這主要得益於銷售成長36%，我們持續維持PCSK9抑制劑類藥物的全球領先地位。美國以外地區的銷售額成長了40%，這主要得益於強勁的患者需求。

In the U.S., we continue to see strength in new patient starts with new-to-brand prescriptions growing 54% quarter-over-quarter helped by favorable pharmacy benefit manager formulary changes. U.S. volume growth demonstrates that we've made good progress against our strategy to provide Repatha at an affordable price to patients, particularly those with Medicare Part D coverage. This acceleration in Medicare Part D growth has increased our exposure to the so-called doughnut hole, which creates some negative impact on overall net price.

在美國，新患者用藥量持續強勁成長，新處方量較上季成長54%，主要得益於藥品福利管理機構（PBM）的處方集調整。美國銷售成長表明，我們在以可負擔的價格向患者（尤其是參加聯邦醫療保險D部分計劃的患者）提供Repatha的策略方面取得了良好進展。聯邦醫療保險D部分計畫的加速成長也增加了我們受「甜甜圈漏洞」（即健保報銷額度上限）影響的風險，這對整體淨價產生了一定的負面影響。

We remain confident in our ability to grow Repatha globally to address the significant unmet medical need in treating high-risk cardiovascular patients.

我們仍有信心在全球發展 Repatha，以滿足治療高風險心血管疾病患者方面尚未滿足的重大醫療需求。

Next to Aimovig, which remains the market leader in the highly competitive CGRP class. Aimovig volumes grew 20% year-over-year in the first quarter with a 45% average total prescription share and 38% average new-to-brand prescription share. Year-over-year net selling price declined, primarily driven by increased rebates to maintain patient access. Unfortunately, millions of patients suffering from migraine are sub-optimally treated with older, less effective therapies. Given the head-to-head data we've generated showing Aimovig's superiority against topiramate, we're confident we can help many more patients suffering from chronic migraine.

在競爭激烈的CGRP類藥物中，Aimovig依然維持著市場領先地位。 Aimovig第一季的銷售量年增20%，平均處方總量佔45%，新藥處方量佔38%。淨售價年減，主要原因是為維持患者用藥可及性而提高了折扣。遺憾的是，數百萬偏頭痛患者仍在接受療效不佳的舊療法治療。鑑於我們已獲得的直接比較數據顯示Aimovig優於托吡酯，我們有信心能幫助更多慢性偏頭痛患者。

Turning to our inflammation portfolio where Otezla has demonstrated a robust safety and efficacy profile with over 6 years of real-world experience in market with more than 500,000 patients treated globally. Enbrel similarly has served millions of patients globally since 1998. Otezla sales were $476 million in the quarter. Volume growth was 9%, driven primarily by 11% total prescription growth in the U.S. Otezla remains the market-leading branded systemic medication for psoriasis with an approximately 30% share of first-line treatment. However, new-to-brand prescription volume remained flat as COVID-19 continued to suppress the diagnosis and treatment of psoriasis patients.

再來看我們的發炎產品組合，Otezla 已展現出強大的安全性和有效性，擁有超過 6 年的真實世界市場經驗，全球已有超過 50 萬名患者接受治療。 Enbrel 自 1998 年以來也已為全球數百萬患者提供服務。本季 Otezla 的銷售額為 4.76 億美元。銷量成長 9%，主要得益於美國處方總量成長 11%。 Otezla 仍然是銀屑病市場領先的品牌系統性藥物，約佔第一線治療市場份額的 30%。然而，由於 COVID-19 疫情持續抑制乾癬患者的診斷和治療，新藥處方量保持穩定。

Year-over-year growth was also negatively impacted given pandemic-related inventory stocking in Q1 of 2020. Otezla has more than 90% commercial payer coverage in the U.S. without requiring a biological step and is an affordable, safe and efficacious option for psoriasis and psoriatic arthritis patients. We see attractive growth opportunities for Otezla as the pandemic recovery progresses. In addition, geographic expansion and the anticipated approval later this year of the mild to moderate psoriasis indication will contribute to future Otezla growth.

受2020年第一季疫情相關庫存積壓的影響，年增率也受到負面影響。 Otezla在美國的商業保險覆蓋率超過90%，無需生物製劑治療，是乾癬和乾癬關節炎患者經濟、安全且有效的治療選擇。隨著疫情的逐步緩解，我們認為Otezla具有良好的成長前景。此外，地理擴張以及預計今年稍後獲準用於治療輕度至中度乾癬，都將有助於Otezla未來的成長。

In 2021, year-over-year comparisons for Enbrel are adversely impacted by $255 million of favorable estimated sales deductions that were recorded in 2020, $115 million of which were in Q1 of 2020. In the quarter, Enbrel sales decreased 20% year-over-year with declines in both unit volume and net selling price. Moving forward, we expect volume and net price trends to continue.

2021年，恩利（Enbrel）的年比業績受到2020年計入的2.55億美元有利銷售額扣除的影響，其中1.15億美元計入2020年第一季。該季度，恩利的銷售額年減20%，銷量和淨售價均下滑。展望未來，我們預期銷售量和淨售價的下滑趨勢將持續。

Parsabiv sales decreased 55% year-over-year driven by 65% volume declines. With Parsabiv inclusion in the end-stage renal disease bundle in the U.S., we have seen dialysis clinics quickly implement new treatment protocols, switching patients from Parsabiv to generic cinacalcet.

受銷量下降65%的影響，Parsabiv的銷售額較去年同期下降了55%。由於Parsabiv已被納入美國末期腎病治療方案，我們看到透析中心迅速實施了新的治療方案，將患者從Parsabiv轉為使用通用名藥物西那卡塞。

Switching to biosimilars. Q1 sales were $570 million driven by strong volume growth, which was partially offset by declines in net selling price. We continue to hold leading biosimilar shares in Europe for AMGEVITA and in the U.S. for MVASI and KANJINTI, where we saw average shares of 50% and 43%, respectively, in Q1. For the remainder of the year, we expect biosimilar volume growth to be offset by declines in net selling price due to increased competition. Longer term, growth for biosimilars will come from expansion of existing products to new markets and launches of additional biosimilar molecules such as AMGEVITA in the U.S. and biosimilars for SOLIRIS, STELARA and EYLEA.

轉向生物類似藥。第一季銷售額達5.7億美元，主要得益於強勁的銷售成長，但部分被淨售價下降所抵銷。我們繼續持有歐洲生物相似藥AMGEVITA以及美國生物相似藥MVASI和KANJINTI的領先市場份額，第一季平均市佔率分別為50%和43%。預計今年剩餘時間裡，由於競爭加劇，生物相似藥的銷售成長將被淨售價下降所抵銷。長期來看，生物相似藥的成長將來自現有產品拓展至新市場以及推出更多生物相似藥分子，例如美國市場的AMGEVITA以及SOLIRIS、STELARA和EYLEA的生物相似藥。

In oncology, Neulasta Onpro remains the preferred long-acting G-CSF, with 54% share of volume in the quarter. In Q1, we surpassed 1 million patients who, with the help of Onpro, were able to receive their G-CSF treatment while reducing the need to return to their doctor's office or other site of care for administration. Consistent with recent trends, Neulasta's U.S. average selling price declined 30% on a year-over-year basis, and we expect this trend to continue throughout 2021 driven by intensifying competition.

在腫瘤治療領域，Neulasta Onpro 仍然是首選的長效粒細胞集落刺激因子 (G-CSF) 製劑，本季市佔率高達 54%。第一季度，我們幫助超過 100 萬名患者接受了 Onpro 治療，從而減少了他們返回診所或其他治療機構接受給藥的次數。與近期趨勢一致，Neulasta 在美國的平均售價年減了 30%，我們預計在競爭加劇的推動下，這一趨勢將在 2021 年持續下去。

XGEVA sales decreased 3% year-over-year for the first quarter as volume growth in Asia was offset by lower net selling price in that region. U.S. unit volumes declined year-over-year driven by demand impacts in January and February, with recovery beginning in March and into April.

XGEVA第一季銷售額年減3%，主要原因是亞洲地區銷售成長被該地區淨售價下降所抵銷。受1月和2月需求下滑的影響，美國市場銷量較去年同期下降，3月至4月開始復甦。

KYPROLIS sales decreased 10% year-over-year for the first quarter as the pandemic has suppressed the number of new patients starting treatment for multiple myeloma. Moving forward, we expect promotion to drive growth in second line and beyond as a result of our launch of the combination indication of KYPROLIS and DARZALEX plus dexamethasone or DKD. The combination of KYPROLIS with SARCLISA and dexamethasone, or Isa-Kd ,was also approved in the quarter.

受疫情影響，多發性骨髓瘤新患者數量減少，導致KYPROLIS第一季銷售額年減10%。展望未來，隨著KYPROLIS聯合DARZALEX和地塞米松（DKD）的聯合療法上市，我們預期推廣活動將推動二線及後續治療領域的成長。此外，KYPROLIS聯合SARCLISA和地塞米松（Isa-Kd）的聯合療法也在本季獲得批准。

As Bob mentioned, our team is ready to launch sotorasib or LUMAKRAS upon approval, and we are excited to establish it as a foundational therapy for patients with advanced lung cancer. We've already launched our biomarker assist program, which removes access barriers to testing and helps appropriate patients without a pocket cost. And we're also preparing for the launch of tezepelumab with our partner, AstraZeneca, and are enthusiastic about the prospect of having a therapy that can help treat the more than 2.5 million people in the world living with severe uncontrolled asthma.

正如鮑勃所提到的，我們的團隊已做好準備，一旦索托拉西布（Sotorasib）或LUMAKRAS獲得批准，我們將立即推出。我們很高興能將其確立為晚期肺癌患者的基礎療法。我們已經啟動了生物標記輔助項目，該項目旨在消除檢測障礙，幫助符合條件的患者免費接受檢測。此外，我們也正在與合作夥伴阿斯特捷利康共同籌備tezepelumab的上市，並對這款有望幫助全球超過250萬重度未控制氣喘患者的療法充滿期待。

Overall, I'm pleased with our Q1 execution given the pandemic-related disruption of new patient diagnoses and treatment, and we'll continue our focused execution during Q2 and are projecting recovery over the second half of the year.

總體而言，考慮到疫情對新患者診斷和治療造成的干擾，我對我們第一季的執行情況感到滿意，我們將繼續在第二季度集中精力執行，並預計下半年將實現復甦。

With that, I'll turn it to Dave.

接下來，我將把麥克風交給戴夫。

Thanks, Murdo, and good afternoon, everyone. I'll begin with 2 new programs that are strong strategic fits within our portfolio.

謝謝默多，大家下午好。我先介紹兩個與我們產品組合高度契合的新項目。

First, we are excited to welcome our new colleagues from Five Prime therapeutics and begin work on bemarituzumab. The integration is going well, and we have hit the ground running with Phase III planning activities. As Bob mentioned, we received breakthrough therapy designation from FDA and look forward to discussions with regulators on the development program, including Phase III in the near future. We will also investigate bemarituzumab in other indications where FGFR2b may play a role, including squamous non-small cell lung cancer, and we'll have more to say on the entire development program as those plans are finalized.

首先，我們非常高興地歡迎來自 Five Prime Therapeutics 的新同事加入我們，並開始 bemarituzumab 的研發工作。整合進展順利，我們已迅速啟動 III 期臨床試驗的規劃工作。正如 Bob 所提到的，我們已獲得 FDA 的突破性療法認定，並期待與監管機構就研發項目展開討論，包括近期啟動 III 期臨床試驗。我們也將研究 bemarituzumab 在 FGFR2b 可能發揮作用的其他適應症中的應用，例如鱗狀非小細胞肺癌。待相關計畫最終確定後，我們將公佈更多關於整個研發項目的資訊。

In inflammation, I would like to highlight our acquisition of Rodeo Therapeutics and their 15 prostaglandin dehydrogenase program, which was motivated by compelling preclinical data from Rodeo and valuable insights from deCODE. This is a nice illustration of our use of human genetic data to inform drug discovery and development.

在發炎領域，我想重點介紹我們收購 Rodeo Therapeutics 及其 15 種前列腺素脫氫酶目標計畫的案例。此次收購的動機源自於 Rodeo 提供的令人信服的臨床前數據以及 deCODE 提供的寶貴見解。這很好地體現了我們如何利用人類遺傳數據來指導藥物發現和開發。

The LUMAKRAS program continues to advance with several regulatory milestones in the first quarter, including global submissions for advanced non-small cell lung cancer and a priority review from FDA with a regulatory action date of August 16. We are having productive interactions with the FDA and multiple other regulatory agencies that will include Japan with today's anticipated submission, and we look forward to making LUMAKRAS available to patients as soon as possible. We are also pleased to receive temporary authorization for use status in France. This designation is to promote fast access to innovative medicines before marketing authorization and conventional access, and we have received a large number of requests.

LUMAKRAS計畫在第一季度取得了多項監管里程碑式的進展，包括已向全球提交晚期非小細胞肺癌的上市申請，並獲得FDA的優先審查資格，預計審批結果將於8月16日公佈。我們與FDA及其他多家監管機構（包括即將於今日提交申請的日本監管機構）保持著富有成效的溝通，並期待盡快將LUMAKRAS推向市場。此外，我們很高興獲得法國的臨時使用授權。該授權旨在促進創新藥物在獲得上市許可和常規治療途徑之前快速進入市場，目前已收到大量申請。

In the clinical development program, we completed enrollment in the Phase III study versus docetaxel in advanced non-small cell lung cancer. Based on the overall efficacy and safety profile of LUMAKRAS and discussions with regulators we reduced the sample size in this study while maintaining appropriate statistical power to assess the progression-free survival primary end point. The time lines of the study have not changed as the primary endpoint remains event-driven.

在臨床開發項目中，我們已完成LUMAKRAS與多西他賽治療晚期非小細胞肺癌的III期臨床試驗的患者招募。基於LUMAKRAS的整體療效和安全性，並與監管機構進行討論後，我們在保持適當統計效力以評估無進展生存期這一主要終點的前提下，減少了該研究的樣本量。由於主要終點仍為事件驅動型終點，因此研究的時間安排保持不變。

While we have demonstrated that the 960 milligram dose is safe and efficacious in advanced non-small cell lung cancer, we continue to explore different doses and regimens as is common in oncology drug development. As part of this effort, we are initiating a new cohort to determine whether a once-daily oral dose of 240 milligrams maintains the safety and efficacy profile of the 960-milligram dose in patients with advanced non-small cell lung cancer. Should a lower dose be safe and efficacious as 960 milligrams, it may further enhance the patient experience with once-daily LUMAKRAS. We expect the results from this study in late 2022 or early 2023 and do not expect any impact on the time lines of our ongoing priority review.

雖然我們證實960毫克劑量對晚期非小細胞肺癌安全有效，但我們仍會像腫瘤藥物研發中常見的做法一樣，繼續探索不同的劑量和給藥方案。作為這項工作的一部分，我們正在啟動一項新的隊列研究，以確定每日一次口服240毫克劑量是否能保持與960毫克劑量相同的安全性和有效性。如果較低劑量與960毫克一樣安全有效，則可望進一步改善患者每日一次服用LUMAKRAS的體驗。我們預計這項研究的結果將於2022年底或2023年初公佈，並且預計不會對我們正在進行的優先審查的進度造成任何影響。

We also continue to make good progress in evaluating combination regimens. Efficacy cohorts are underway for our MEK inhibitor, EGFR antibody and oral EGFR inhibitor combinations, and we expect to present updates on these regimens at medical meetings in the second half of the year. We continue to evaluate doses and regimens to find the optimal options for patients in our other combinations, including PD-1 and SHIP2.

我們在評估聯合治療方案方面也持續取得良好進展。目前正在進行MEK抑制劑、EGFR抗體和口服EGFR抑制劑合併治療方案的療效隊列研究，預計將在今年下半年的醫學會議上公佈這些方案的最新進展。我們也持續評估其他合併治療方案（包括PD-1和SHIP2合併治療）的劑量和給藥方案，以期為患者找到最佳選擇。

Finally, we are initiating triplet cohorts in colorectal cancer of LUMAKRAS with standard of care chemotherapy and either an anti-EGFR or anti-VEGF antibody.

最後，我們正在對 LUMAKRAS 大腸直腸癌患者啟動三聯體隊列研究，採用標準治療化療，並分別使用抗 EGFR 或抗 VEGF 抗體。

In our BiTE programs, we have initiated several new studies, including new indications for AMG 160, targeting PSMA in non-small cell lung cancer and AMG 757, targeting DLL3, now also being investigated in neuroendocrine prostate cancer. Details on these and other development programs, including small molecules, can be found in our press release.

在我們的BiTE計畫中，我們啟動了多項新研究，包括AMG 160（靶向PSMA，用於治療非小細胞肺癌）和AMG 757（靶向DLL3，目前也在研究其在神經內分泌前列腺癌中的應用）的新適應症。有關這些項目和其他研發項目（包括小分子藥物）的詳細信息，請參閱我們的新聞稿。

Turning to tezepelumab. Developed in collaboration with AstraZeneca, the Phase III NAVIGATOR data were well received by clinicians, and additional analyses will be presented at the American Thoracic Society Meeting in May. We remain on track to submit regulatory filings this quarter and believe the data support tezepelumab as a first-line biologic therapy for a broad population of patients with severe uncontrolled asthma. We are also investigating other indications with Phase II studies in COPD and chronic spontaneous urticaria and, most recently, a Phase III study for chronic rhinosinusitis with nasal polyps.

接下來談談tezepelumab。該藥物由我們與阿斯特捷利康合作開發，其III期NAVIGATOR研究數據獲得了臨床醫生的好評，更多分析結果將於5月在美國胸腔科協會年會上公佈。我們仍按計劃在本季度提交監管文件，並相信這些數據支持tezepelumab作為一線生物製劑，用於治療廣泛的重度未控制氣喘患者群體。我們也正在探索其他適應症，包括慢性阻塞性肺病（COPD）和慢性自發性蕁麻疹的II期研究，以及最近啟動的針對伴有鼻息肉的慢性鼻竇炎的III期研究。

Finally, on Otezla, we submitted a supplemental new drug application to FDA based on the Phase III ADVANCE study in mild to moderate psoriasis. The positive results from ADVANCE were presented at the American Academy of Dermatology, or AAD, meeting a few days ago.

最後，關於 Otezla，我們根據針對輕度至中度銀屑病的 III 期 ADVANCE 研究，向 FDA 提交了補充新藥申請。 ADVANCE 研究的正面結果已於幾天前在美國皮膚病學會 (AAD) 會議上公佈。

In closing, I'd like to thank our staff for continuing to deliver for patients. Bob?

最後，我要感謝我們的員工一直以來為病人提供的優質服務。鮑伯？

Okay. Erica, thank you. Let's turn now to Q&A, and perhaps you could remind our callers of the procedure for asking questions. Thanks.

好的。艾麗卡，謝謝你。現在我們進入問答環節，你能不能提醒來電者提問的流程？謝謝。

(Operator Instructions) Your first question is from Geoff Meacham with Bank of America.

（操作員說明）您的第一個問題來自美國銀行的傑夫·米查姆。

I had a question on Otezla, the head-to-head against deucravacitinib at AAD showed some pretty meaningful differentiation. I just wanted to ask from maybe a commercial perspective how does that data set along with the advanced data change you're thinking about the positioning of Otezla in the marketplace with respect to psoriasis.

我有一個關於Otezla的問題。在AAD大會上，Otezla與deucravacitinib的頭對頭試驗顯示出了相當顯著的差異。我想從商業角度請教一下，這些數據以及後續的高級數據會如何改變您對Otezla在銀屑病市場定位的看法？

Murdo?

默多？

Yes. Thanks, Geoff, for the question. The first thing I would just reiterate is that we anticipated that the Deuc data would indeed show what they did show. And we assume that in the model that we put together for the transaction, and we've assumed that for the balance of this year.

是的。謝謝Geoff的提問。首先我想重申的是，我們預期Deuc的數據確實會呈現出最終呈現的結果。我們在為這筆交易建立的模型中也做出了同樣的假設，而我們今年剩餘時間也一直沿用這個假設。

What I would say is that we continue to believe that Otezla is really ideally positioned in the first-line prebiologic psoriasis market. As I mentioned in my prepared remarks, we've been on the market for 6 years now. We have in-market cumulative patient experience with over 500,000 individuals globally. We have excellent commercial and payer coverage at over 90% of covered lives. And we continue to make really good progress, holding a 30% share in the market with really outstanding customer-facing capabilities.

我想說的是，我們仍然堅信Otezla在乾癬一線生物製劑前治療市場中佔據著非常理想的地位。正如我在準備的演講稿中提到的，我們的產品已經上市6年了。我們在全球擁有超過50萬名患者的累計市場經驗。我們的商業保險和健保覆蓋率都非常出色，超過90%的投保族群都獲得了健保覆蓋率。而且，我們持續取得顯著進展，目前佔據30%的市場份額，並擁有卓越的客戶服務能力。

The other thing that we, of course, look at is positioning in the market and how that holds up against not just Deuc but other competitors. And we think that we really are the first kind of option prebiologic post-topical. And dermatologists have become very comfortable using Otezla that way. Payer coverage is consistent with that position in the market. And with the mild -- pending mild to moderate indication data, which were presented at the same AAD meeting, which look quite compelling, we expect to be able to expand our utilization of Otezla and psoriasis population in the milder patient type.

當然，我們也會關注市場定位，以及它與Deuc和其他競爭對手相比的優勢。我們認為，我們確實是首款在生物製劑治療前、局部用藥後使用Otezla的替代療法。皮膚科醫生已經非常習慣以這種方式使用Otezla。醫保覆蓋範圍也與我們的市場定位相符。此外，在同一屆美國皮膚病學會（AAD）會議上公佈的輕度至中度適應症數據（目前正在等待中）也相當令人信服，我們預計能夠擴大Otezla在輕度乾癬患者群體中的應用。

So overall, we like our position in the market. The way I see it is we still have to see how the full detailed safety data look for the TYK2 product given that it is part of the JAK family. And it took 6 years and over 200,000 patients for us to understand the Xeljanz safety profile. So I think there's a lot still to be understood here but not necessarily the safety and efficacy of Otezla.

總的來說，我們對目前的市場地位感到滿意。我認為，鑑於TYK2屬於JAK家族，我們仍需進一步了解其完整的安全數據。我們花了6年時間，納入超過20萬名患者，最後才了解了託法替尼（Xeljanz）的安全性。因此，我認為Otezla還有很多需要了解的地方，但其安全性和有效性目前尚不完全清楚。

Your next question is from Michael Yee with Jefferies.

下一個問題來自傑富瑞集團的麥可葉。

I had a question maybe for David. You had a nice update and comments on KRAS. Maybe you could just put some context around the timing of data now for the second half around MEK, maybe talk about what drives the timing of that and disclosure. And then the comment around 240 versus 960, I think there'll be different ways to interpret that. Maybe you can make a comment about that because I thought 960 was pretty well tolerated and it's got a good profile. So maybe we'll have some comments on that, that would be great.

我有個問題想問David。你之前對KRAS的進展做了很好的更新和評論。你能不能解釋一下下半年MEK數據公佈的時間安排，談談影響數據公佈和揭露時間的因素？還有關於240和960劑量對比的評論，我覺得會有不同的解讀。你能不能就此發表一下看法，因為我覺得960的耐受性很好，而且安全性也不錯。所以，如果你能就此發表一些看法，那就太好了。

Yes. Thanks, Mike. Both great questions. I think our anticipation is that at meetings right after the second half -- right into the start of the second half of the year, we'll start to see some of the cohort data that we outlined, MEK and then both EGFR antibody and small molecule inhibitor combinations. And you can probably see those come out sequentially over the second half of the year as we accumulate data. I would say that the combination therapy programs are moving along quite rapidly. And as we mentioned, we've opened some new triplet combinations. So I feel very good about where we are in the status of combination regimens.

是的，謝謝，麥克。兩個問題都很好。我們預計，在下半年結束後的會議上——也就是下半年初——我們將開始看到一些我們先前概述的隊列研究數據，包括MEK抑制劑以及EGFR抗體和小分子抑制劑的組合療法。隨著數據的積累，您可能會在下半年陸續看到這些數據公佈。我認為聯合療法計畫進展相當迅速。正如我們之前提到的，我們已經啟動了一些新的三重療法。因此，我對聯合療法的現狀感到非常滿意。

In terms of the dose comparison study, we've now got long-term data from both our Phase I trial as well as the Phase II trial, updated target coverage, information, pharmacokinetics as well as, of course, efficacy and safety data. And based on modeling, we wondered could we achieve adequate target coverage at 250 and preserve potentially the same efficacy profile that we've seen at 960 milligrams. And so that's just a question that we're going to ask. It's quite common to continue dose exploration in oncology molecules. And I would view this as par for the course.

就劑量比較研究而言，我們現在擁有 I 期和 II 期試驗的長期數據，包括更新的標靶覆蓋率、資訊、藥物動力學以及療效和安全性數據。基於模型，我們想知道是否能在 250 毫克劑量下達到足夠的標靶覆蓋率，並保持與 960 毫克劑量相同的療效。這正是我們將要探討的問題。在腫瘤藥物領域，持續探索劑量是很常見的，我認為這是常規做法。

We are very pleased with the tolerability profile. And as you pointed out, at 960 milligrams, we've had an outstanding experience. In fact, this is one of the best tolerated drugs that I've been involved with in 30 years in oncology drug development. And that's not really what a driver is here, but can we potentially get by with efficacy at a lower 240-milligram dose and enhance the patient experience?

我們對藥物的耐受性非常滿意。正如您所指出的，960毫克的劑量效果極佳。事實上，這是我在腫瘤藥物研發領域30年來參與過的耐受性最好的藥物之一。雖然這並非我們此次研發的重點，但我們能否在維持療效的前提下，將劑量降低至240毫克，同時提升病患的用藥體驗呢？

Your next question is from Jay Olson with Oppenheimer.

下一個問題來自奧本海默公司的傑伊·奧爾森。

Curious about the Phase II data for Olpasiran that you expect in the first half of next year. Can you just talk about what sort of signals you'll be looking for in that data in terms of your plans to design a Phase III study, and any potential points of differentiation from pelacarsen?

我對您預計明年上半年公佈的 Olpasiran 二期臨床試驗數據很感興趣。您能否談談在設計三期臨床試驗時，您會從這些數據中尋找哪些訊號？以及 Olpasiran 與 pelacarsen 之間可能存在的差異？

Yes. Thanks, Jay. And for those who may not know off the top of their heads what olpasiran is, this was formerly AMG 890. It's a small interfering RNA designed to lower lipoprotein A levels in patients with atherosclerotic cardiovascular disease where elevated Lp(a) may be a driver. As we noted, we completed enrollment in what's a robust Phase II trial that actually completed enrollment ahead of schedule.

是的，謝謝，傑伊。或許有些人不太了解olpasiran是什麼，它以前叫AMG 890。它是一種小幹擾RNA，旨在降低動脈粥狀硬化性心血管疾病患者的脂蛋白A水平，因為Lp(a)水平升高可能是導致這些疾病的因素之一。正如我們之前提到的，我們已經完成了這項嚴謹的II期臨床試驗的受試者招募工作，而且實際上提前完成了招募。

And what we'll be looking for as we unveil those data, Jay, are, first of all, longer-term follow-up, meaning sufficient long-term suppression of Lp(a) levels. And our targets would be in the range of the Phase I data that we presented last November at the American Heart Association meeting and then, of course, additional safety data. And of course, we are exploring different dose levels as is pretty much standard in a program like this. And so this would be in part for dose selection for Phase III going forward. We are very actively engaged already in Phase III planning and what the design of that sort of trial may look like. Based on the data that we've seen to date, one of our goals may be relatively infrequent dosing given the duration of effect that we observed in the Phase I trial, and that's one thing that we'll be taking a close look at as well in Phase II.

傑伊，當我們公佈這些數據時，首先關注的是長期追蹤結果，也就是Lp(a)水平能否得到充分的長期抑制。我們的目標將與去年11月在美國心臟協會會議上公佈的I期數據相符，當然，我們將關注更多的安全性數據。此外，正如這類研究項目通常的做法，我們也在探索不同的劑量水平。這部分是為了確定未來III期試驗的劑量。我們已經積極參與III期試驗的規劃，並研究該試驗的設計方案。根據我們目前掌握的數據，考慮到I期試驗中觀察到的療效持續時間，我們的目標之一可能是採用相對低頻給藥，這也是我們將在II期試驗中重點關注的方面。

Your next question is from Matthew Harrison with Morgan Stanley.

下一個問題來自摩根士丹利的馬修·哈里森。

Murdo, I was wondering if you could just comment in a little more detail on the Repatha trends. It looks like we're really starting to see the product break out a little bit here and not seeing some of those first quarter gross to net issues that you've sort of experienced in the past couple of years. Do you think you're at a point now where you're going to get substantial Part D penetration and also see rest of world penetration? Maybe you could just comment on your outlook there.

Murdo，我想請您更詳細地談談Repatha的銷售趨勢。看起來這款產品似乎開始有所突破，不再像過去幾年那樣出現第一季毛利與淨利之間的波動。您認為現在Repatha在聯邦醫療保險D部分（Part D）的滲透率會大幅提升，並且有望在全球其他地區也獲得滲透嗎？您能否就此談談您的展望？

Yes. Thank you, Matthew. We are pleased obviously with the quarter for Repatha, and it's been a bit of a journey getting here and trying to ensure that patients have affordable access to Repatha, particularly in Medicare Part D, as you point out. I would say that we are anticipating -- with one exception, we are anticipating relatively stable net price for the remainder of the year. And the exception that I'm pointing out is that as we expand our penetration of Medicare Part D, we will have some drag on our net price as a function of patients entering and staying in the doughnut hole for a period of time. So that's the one downside of helping patients in Medicare Part D.

是的，謝謝你，馬修。我們對瑞百安（Repatha）本季的業績非常滿意，正如你所指出的，我們一路走來並努力確保患者能夠負擔得起瑞百安，尤其是在聯邦醫療保險D部分（Medicare Part D）中，這確實是一項艱辛的歷程。我想說的是，我們預計——除一個例外情況外——今年剩餘時間的淨價將保持相對穩定。我提到的例外情況是，隨著我們在聯邦醫療保險D部分（Medicare Part D）的覆蓋率不斷提高，由於部分患者會進入並停留在「甜甜圈漏洞」（doughnut hole）階段，我們的淨價會受到一定程度的拉動。所以，這是幫助聯邦醫療保險D部分（Medicare Part D）患者的唯一弊端。

There is still a coverage gap in that benefit. And of course, the -- given the durability of treatment and the chronic nature of Repatha, they can be in that coverage gap for quite a bit. So we do have more exposure to the doughnut hole over time. But as you could tell from the first quarter, we were more than able to offset that small drag on net price. And we anticipate that we'll continue to penetrate that patient population given the very strong payer coverage we have there with -- between commercial and Medicare, we've got over 80% covered lives for this important product.

該福利仍存在覆蓋缺口。當然，考慮到瑞百安（Repatha）治療的持久性和慢性病特性，患者可能會在覆蓋缺口中停留相當長的時間。因此，隨著時間的推移，我們確實會面臨更大的自付額缺口風險。但正如您從第一季的業績所看到的，我們完全能夠抵銷淨價方面的這一小幅下滑。鑑於我們強大的支付方覆蓋率——包括商業保險和聯邦醫療保險（Medicare），我們預計我們將繼續拓展這一患者群體，目前該重要產品的覆蓋率已超過80%。

And there are still millions of patients out there who are sub-optimally treated for their hyperlipidemia given that they're at very high risk of cardiovascular events. So -- and globally, we're seeing some really strong performance in Europe, in the Americas. China is doing quite well despite not having NRDL listing, and we continue to make inroads in Japan where we are the only PCSK9 on the market.

目前仍有數百萬高血脂患者未得到最佳治療，因為他們面臨極高的心血管事件風險。因此，在全球範圍內，我們在歐洲和美洲都看到了非常強勁的市場表現。儘管尚未獲得國家藥品監管部門（NRDL）的批准，但在中國市場也表現良好。此外，我們在日本市場持續取得進展，目前我們是日本市場上唯一的PCSK9抑制劑。

Your next question is from Yaron Werber with Cowen & Company.

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

Great. David, if you don't mind, I just have a follow-up question as well about LUMAKRAS relating to PD-1 combo specifically. I think you've said in the past that you haven't gotten to the MTD on both drugs. As you tested in combination, it sounds like you're continuing to explore dose and schedule. You've also recently talked about sequential therapy. So we're just trying to say, are we actually going to get data in the second half? And why are you testing sequential therapy? What are you trying to see?

好的。 David，如果您不介意的話，我還有一個關於LUMAKRAS與PD-1聯合療法相關的後續問題。我記得您之前說過，這兩種藥物都還沒有達到最大耐受劑量（MTD）。既然您進行了聯合治療試驗，聽起來您還在繼續探索劑量和給藥方案。您最近也談到了序貫療法。所以我們想問的是，我們真的能獲得下半年的數據嗎？為什麼要測試序貫療法？您想了解什麼？

Yes. Thanks, Yaron. We're continuing to look at a variety of approaches in combination with PD-1s. Whether that's in combination or sequentially, I think, it's fair to say a number of small molecules, EGFR inhibitors, BRAF inhibitors, MEK inhibitors, had challenges, combining with PD-1s. And I think there's a fair amount to work out here. We are -- we'll provide updates. I don't know if we'll have data that's robust enough to share in the second half of the year. That's possible. But I don't want to promise that. But certainly, we'll provide guidance as those different regimens move along, and sequential therapy may be actually a preferred approach here.

是的，謝謝，Yaron。我們正在繼續研究多種與PD-1抑制劑合併使用的治療方案。無論是合併用藥或序貫用藥，我認為可以肯定的是，許多小分子藥物，例如EGFR抑制劑、BRAF抑制劑和MEK抑制劑，在與PD-1抑制劑合併使用時都遇到了挑戰。我認為這裡還有很多問題需要解決。我們會及時更新進展。我不知道下半年我們是否能獲得足夠可靠的數據來分享。這並非不可能，但我不能做出這樣的承諾。當然，隨著不同治療方案的推進，我們會提供指導，而序貫療法或許才是更優的選擇。

Your next question is from Terence Flynn with Goldman Sachs.

下一個問題來自高盛的 Terence Flynn。

Maybe just one follow-up on that, Dave. I was just wondering, does the 940 mg dose exploration have to do with this question on how to best combine KRAS with a PD-1? And then my other question, I just was wondering, Bob or Peter, if you could comment on the tax proposals coming out of D.C. and any implications for your Puerto Rico -- some of the tax benefits you get out of Puerto Rico on the manufacturing side?

戴夫，或許我還有一個後續問題。我只是想知道，940毫克劑量的探索是否與如何將KRAS與PD-1最佳結合這一問題有關？另外，鮑勃或彼得，我想請教一下你們能否就華盛頓特區提出的稅收提案以及這些提案對你們波多黎各的影響發表一下看法——比如你們在波多黎各製造業方面獲得的稅收優惠？

Thanks, Terence. I'll take the first part of that question. Yes, the 240-milligram dose comparison study doesn't have really anything to do with the combinations dosing. As you're aware, in combination regimens in oncology, one typically explores a range of doses potentially of all of the members of that combination regimen, depending on what the backbone may be. But this is really a monotherapy exploration and, again, determined to see whether we can preserve efficacy at a lower dose at this lower 240-milligram dose.

謝謝，特倫斯。我先回答你問題的第一部分。是的，240毫克劑量對照研究與合併用藥的劑量方案並無直接關係。如你所知，在腫瘤聯合治療方案中，通常會根據基礎方案，探索該方案中所有藥物的一系列劑量。但這項研究其實是對單藥治療的探索，旨在觀察我們能否在較低的240毫克劑量下維持療效。

On the tax front, Peter, why don't you share your thoughts?

彼得，關於稅務方面，為什麼不分享一下你的看法呢？

I will. Terence, a very good question there. And look, I think it's premature to speculate on this. We expect the administration's proposal to be subject, I think, as everybody does, to significant debate within Congress and other stakeholders. Rest assured, we're active in Washington to ensure that our position and our taxes should continue to be competitive and should continue to really encourage innovation in the United States as well heard and understood. And we are very supportive, as you can imagine, of incentives to encourage manufacturing in the United States in the U.S. territory and Puerto Rico.

好的。特倫斯，你問得很好。我覺得現在就此妄下斷言還為時過早。我們預計，正如大家所預料的那樣，政府的提案將會在國會和其他利益相關者內部引發激烈的辯論。請放心，我們正在華盛頓積極遊說，以確保我們的政策和稅收政策繼續保持競爭力，並繼續切實有效地鼓勵美國的創新，讓各方都能聽到並理解我們的努力。正如你所想，我們非常支持各項激勵措施，以鼓勵在美國本土、美國屬地和波多黎各發展製造業。

And Terence, I would just let you know that our tax leader, Jackie Crouse has much expertise in the area of Puerto Rico, not just around taxes, but just overall into how the economy down there functions and so forth. She's called upon regularly by the legislature for advice and counsel. Thanks again for the question.

特倫斯，我還要告訴你，我們的稅務負責人傑基·克勞斯在波多黎各領域擁有豐富的專業知識，不僅在稅務方面，而且對那裡的經濟運作等等都非常了解。立法機構經常向她諮詢意見。再次感謝你的提問。

Your next question is from Umer Raffat with Evercore ISI.

您的下一個問題來自 Evercore ISI 的 Umer Raffat。

David, I have a 2-part question on KRAS. First, perhaps if you could just walk us through your thought process on why 240 in particular. Why not 180 or 360? And I say that in the context of having seen responses as low as 180. Perhaps you could even give us a flavor for what the PK curves look like around the 240 doses above and below.

David，我有一個關於KRAS的問題，分成兩個部分。首先，您能否解釋一下您為什麼選擇240這個劑量？為什麼不是180或360？我之所以這麼問，是因為我看過低至180的劑量也有效。能否再簡單介紹一下240劑量上下對應的藥物動力學曲線？

And secondly, I recall back when the Phase III was initiated for KRAS, the powering math was really directed at OS, not PFS, even though the primary end point is PFS. I realize the conversations with FDA have moved towards PFS and looks like the new powering is more than reasonable for PFS. But I do want to understand the evolution and thought process away from OS and what we can reasonably expect on p-values around OS with data as it emerges.

其次，我記得KRAS突變基因三期臨床試驗啟動之初，其統計效力計算主要針對總存活期（OS），而非無惡化存活期（PFS），雖然PFS是主要終點。我知道與FDA的討論已經轉向PFS，而且新的統計效力計算似乎也更適合PFS。但我確實想了解從OS轉向PFS的想法和流程，以及隨著資料的不斷湧現，我們能夠合理預期OS的p值會是多少。

Yes. Thanks, Umer. Good questions. The 240-milligram dose was chosen based on modeling that we've done that really takes account of all of the dose levels, pharmacokinetic data, target coverage data or accumulated preclinical data regarding efficacy at different target coverage levels. And this was really chosen as a lower bound where we thought we would potentially preserve or could preserve the efficacy that we're seeing at 960 milligrams.

是的，謝謝，Umer。問得好。我們選擇240毫克劑量是基於我們建立的模型，該模型綜合考慮了所有劑量水平、藥物動力學數據、靶點覆蓋率數據以及不同標靶覆蓋率下累積的臨床前療效數據。選擇這個劑量其實是作為下限，我們認為在這個劑量下，我們有可能或能夠保持與960毫克劑量下相同的療效。

In regards to the Phase III trial, as you note, we changed the powering to really -- we have good power on the progression-free survival end point. That was done in concert with regulators. We will be able to take a look at overall survival. The power will be somewhat reduced in terms of the overall survival end point. But I think we'll still have a pretty good sense of what the drug is producing in terms of overall survival. Part of the thinking here as well is to minimize exposure of patients to the docetaxel control arm.

關於III期試驗，正如您所指出的，我們調整了樣本量，因此在無惡化存活期這一終點指標上，我們擁有了良好的統計效力。這是與監管機構共同商定的。我們之後也會關注總存活期。雖然總存活期終點指標的統計效力會略有降低，但我認為我們仍然能夠較為準確地了解該藥物在總存活期方面的效果。此外，我們考慮的重點之一是盡量減少患者接受多西他賽對照組治療的時間。

Your next question is from Mohit Bansal with Citi.

下一個問題來自花旗銀行的莫希特·班薩爾。

And maybe one question for Murdo. So Onpro has done really well during pandemic, could you please remind us how often these contracts are negotiated? And should we expect any reversal in Onpro trends? Or are you seeing anything there as the pandemic subsides?

或許我還有一個問題想問默多。 Onpro在疫情期間表現非常出色，您能否提醒我們這些合約的談判頻率？我們是否應該預期Onpro的發展趨勢會逆轉？或者隨著疫情消退，您是否看到了任何變化？

Thanks, Mohit. The contracts aren't necessarily on a schedule. We have some large networks where we negotiate annually. But we have a lot of smaller what we call value-based accounts where we contract on a much more non-calendarized basis. So they're happening throughout the course of the year.

謝謝，莫希特。合約簽訂並非一定按固定時間表進行。我們有一些大型網絡，每年都會進行談判。但我們也有很多規模較小的、我們稱之為「價值導向型」的客戶，這些客戶的合約簽訂時間沒有固定的時間表。所以，合約簽訂貫穿全年。

And is your question with respect to reversal -- are you asking me about price trends, volume trends? Can you clarify that question?

你的問題是關於價格反轉的嗎？你是在問我價格走勢還是成交量走勢？你能把問題說得更清楚一些嗎？

I mean the trends -- I mean because there was a trend towards using more Onpro versus the PFS given it is taken -- at home product. So do you think there could be some kind of reversal there as the pandemic subsides because then, I mean, patient can come in and then get their shots?

我的意思是，目前的發展趨勢是－因為Onpro的使用量超過了PFS（一種家用注射產品）。那麼，隨著疫情消退，患者可以來診所接種疫苗，您認為這種情況可能會逆轉嗎？

Yes. Thank you for the clarification. Obviously, we're watching that. Clearly, the pandemic was stimulus for many oncologists to think more carefully about the G-CSF treatment that they were going to use in order to help minimize the amount of provider interaction that patients would incur. What we have been doing in the meantime, though, is reinforcing that you actually can improve outcomes by using long-acting G-CSF and using Onpro, in particular.

是的，謝謝您的澄清。我們當然會關注此事。顯然，疫情促使許多腫瘤科醫師更加謹慎地思考他們將要使用的G-CSF治療方案，以盡可能減少病患與醫護人員的接觸。同時，我們一直在強調，使用長效G-CSF，特別是Onpro，確實可以改善治療效果。

So we have a promotional effort that I think is helping strengthen the volume demand curve. The only thing I will continue to point out, though, is with competition comes some price erosion, and we have a new competitor entrant in that category in the long-acting G-CSF category. So we anticipate more net price -- negative evolution through the remainder of the year.

因此，我們所進行的促銷活動我認為有助於提升銷售需求曲線。不過，我還是要強調一點，競爭必然會導致價格下降，而且長效粒細胞集落刺激因子（G-CSF）領域又出現了一個新的競爭對手。因此，我們預計今年剩餘時間內淨價格將繼續走低。

Your next question is from Geoffrey Porges with SVB Leerink.

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

Murdo, could you just discuss the issue of price? Pretty significant negative price effect. First of all, could you tell us whether that's all in the U.S. or whether it's U.S. and ex U.S.? And then secondly, since you, in the U.S., took significant price increases at the end of the year but still have negative price Q-on-Q, it looks like 8% or 9%, is this going to be a trend that persists throughout the year? And then, Bob, perhaps you could comment on what we should be modeling in terms of legislative or executive order changes to pricing going forward. You usually have your finger on the pulse in Washington.

默多，您能談談價格問題嗎？價格受到的負面影響相當顯著。首先，您能否告訴我們，這種情況只發生在美國，還是美國境內外都有影響？其次，鑑於您在美國年底大幅提價，但環比價格仍然下降，降幅似乎在8%到9%之間，這種情況會持續到年底嗎？鮑勃，您能否就未來立法或行政命令可能對價格產生的影響進行建模分析，並談談您的看法？您通常對華盛頓的動態非常了解。

Sure. All right. Thanks. Thanks, Geoff. Let me go first on the overall price evolution in the portfolio. We continue to believe that mid-single-digit net negative price for the portfolio for the year is the right number. That's what we continue to see. What you know and what we experienced probably more than some of our peer companies in the first quarter given the nature of our portfolio is more net negative price evolution because of patients renewing in their benefits and going through benefit reverification and hitting their kind of out-of-pocket resets.

好的。謝謝。謝謝，傑夫。我先談談投資組合的整體價格走勢。我們仍然認為，投資組合全年淨價格為負值（個位數中段）是合理的。我們一直觀察到這種情況。您也知道，鑑於我們投資組合的性質，我們在第一季可能比一些同業公司經歷得更明顯，淨價格下跌幅度更大，這是因為病患續保、進行福利重新核實以及達到自付費用重置的臨界點。

And so our co-pay assistance programs have more drag. We did activate more payer access at the end of last year into this. So we did have, on some brands, some increased payer coverage at the cost of some net price negative evolution. But we do anticipate Q1 being the lowest compare, Q2 a little better, and then Q3 and Q4 being better thereafter.

因此，我們的共付額援助計畫面臨更大的阻力。去年年底，我們確實擴大了支付方的覆蓋範圍。所以，在某些品牌上，我們確實提高了支付方的覆蓋率，但代價是淨價格出現了一些負面影響。不過，我們預計第一季同比數據最低，第二季略有好轉，第三季和第四季將進一步改善。

And Geoff, in Washington, I'm not sure whether executive orders is the concern these days or whether it's something that's attached to reconciliation. If I had to guess, I'd say there's a greater risk that something being attached to reconciliation. But it's still not very clear how this administration and members of the Democratic Party in general want to try to tackle the question of drug pricing this year. So we're continuing to stay very involved, as you would expect. And we have the benefit, I think, of being able to demonstrate just how important innovation is with the progress you see being made against the pandemic. And so we'll continue to stay active and focus on the things that can be done to improve patient access to medicines.

傑夫，在華盛頓，我不確定最近大家關注的是行政命令，還是與預算協調相關的問題。如果非要我猜，我會說與預算協調相關的問題風險更大。但目前還不清楚本屆政府和民主黨成員今年打算如何解決藥品定價問題。所以，正如你所料，我們將繼續積極參與其中。我認為，我們能夠藉此機會，透過對抗疫情所取得的進展，展現創新的重要性。因此，我們將繼續保持積極性，專注於如何改善患者獲得藥物的途徑。

And I think the other thing, Geoff, is to continue to shed light on the role of the middleman and how much of the pharmaceutical dollars now lined up in the hands of the middleman, which I think now, across the country, is just in excess of 50%. I think it actually is at 51% now. So we'll continue to draw attention to that as well.

傑夫，我認為還有一點需要繼續關注，那就是要揭露中間商的角色，以及現在有多少醫藥資金落入了中間商手中。我認為目前全國範圍內，這個比例已經超過50%，實際上我認為已經達到51%。所以我們也會繼續關注這個問題。

Your next question is from Alethia Young with Cantor Fitzgerald.

你的下一個問題來自坎托·菲茨杰拉德的阿萊西亞·楊。

I just wondered if you guys can talk a little bit more about the moderate to severe psoriasis market and how you plan on kind of penetrating with the current commercial sales force you have, especially in light of potential competition that may emerge over time with Bristol. And then just also with the SHIP2 program, is that still underway as a combination for you guys?

我想請你們詳細談談中重度乾癬市場，以及你們計劃如何利用現有的銷售團隊打入這個市場，尤其是在考慮到未來可能出現的來自百時美施貴寶的競爭時。另外，SHIP2專案目前還在進行中嗎？

Maybe I'll just start very quickly, Alethia. SHIP2, yes, that's underway. And we're continuing to work on that combination, more to come. Murdo?

或許我可以很快開始，阿萊西亞。 SHIP2，是的，正在進行中。我們也在繼續研究那個組合，敬請期待更多消息。默多？

Yes. And Alethia, as I mentioned earlier in response to the question on the TYK2 data that were recently presented, we -- as I've mentioned in the past, we have begun primary care promotion for Otezla in the currently labeled mild to moderate patient population and have seen good response there in terms of uptake with 11% TRx year-on-year performance for the quarter. We're pretty pleased with that evolution.

是的。 Alethia，正如我之前在回答關於最近公佈的TYK2數據的問題時提到的，我們已經開始在目前被歸類為輕度至中度患者人群中推廣Otezla，並且看到了良好的反響，本季度處方量同比增長11%。我們對這項進展非常滿意。

What we are seeing is a slowdown in the psoriasis patient population in the newly diagnosed patient population, in particular. And we think this is a direct impact of COVID, causing patients with psoriasis not to see their dermatologist starting really at the beginning of the pandemic. But what's happened is the cumulative effect of this is starting now to impact the patients that have passed through some of the topical options, and we depend on bio-naive patients for our growth. So we are definitely a prebiologic option for dermatologists.

我們觀察到，銀屑病患者群體，尤其是新確診患者群體，成長速度有所放緩。我們認為這是新冠疫情的直接影響，疫情初期，許多乾癬患者就診量減少，無法及時就診。但現在，這種影響的累積效應開始波及那些已經嘗試過一些外用藥物的患者，而我們的增長依賴於未使用過生物製劑的患者。因此，對於皮膚科醫師來說，我們無疑是生物製劑治療前的另一種選擇。

So we are watching that closely, and we think that that could continue to create some softness in the prebiologic psoriasis patient market opportunity into Q2 with recovery thereafter because we are seeing much more patient volume in dermatology offices in March and into April. So we think that things are recovering, but it'll take a while for that cumulative effect of new patient softness to work its way through the market.

因此，我們正在密切關注這一情況，我們認為這可能會在第二季度繼續造成銀屑病生物製劑治療前患者市場機會的疲軟，但之後會有所復甦，因為我們在3月和4月看到皮膚科診所的患者數量大幅增加。所以我們認為市場正在復甦，但新患者需求疲軟的累積效應需要一段時間才能完全消除。

In terms of overall positioning in the market, we continue to think that our safety and efficacy profile is a very attractive option for patients and dermatologists as that first systemic agent prebiologic. And I think really, these days in rheumatology and dermatology, physicians are much more aware of the different categories of options that they have and the different profiles of the different classes of drug. And I think that with recent data in the JAK category, there'll be some speculation and some hesitancy to use a product like the TYK2 as a first bio-naive option to treat patients.

就整體市場定位而言，我們仍然認為，作為首個生物製劑前全身治療方案，我們的安全性和有效性對患者和皮膚科醫生來說極具吸引力。而且我認為，如今在風濕病學和皮膚病學領域，醫生們對不同類型的治療方案以及不同類別藥物的特性有了更深入的了解。我認為，鑑於JAK抑制劑類藥物的最新數據，人們可能會對使用TYK2這類產品作為首個生物製劑前治療方案有所顧慮。

Your next question is from Dane Leone with Raymond James.

您的下一個問題來自 Raymond James 的 Dane Leone。

Congrats on the update and the start to the year. So the question for me, which is a follow-up to some of sotorasib questions, is really -- maybe since people have been asking about fairly specific things, I think what everyone is trying to analyze in some of the updates if we're really only getting longer-term follow-up on your pivotal data set at ASCO is what's the team's view right now of the ability to move sotorasib into the frontline setting in lung.

恭喜您更新了研究進展，也恭喜您新年伊始。我的問題，也是對之前一些關於索托拉西布（sotorasib）問題的後續，是這樣的——或許是因為大家都在問一些比較具體的問題，我想大家在一些更新中試圖分析的是，如果我們在ASCO會議上只能獲得您關鍵數據集的長期隨訪數據，那麼團隊目前對將索托拉西布（sotorasibrasibras）推廣到一線。

A lot of us had thought that you would need a combination -- successful combination with PD-1 to move in the frontline setting. Obviously, we haven't seen you guys start a pivotal data set, and you just said it might take longer to figure out that algorithm. Alternatively, you go down the SHIP2 pathway. Do you, one, have a time line for showing us SHIP2 combination data? And two, is there an alternative path for getting sotorasib into the frontline lung setting that we should be thinking about that we might be missing on this call right now?

我們很多人都認為，要讓 sotorasib 進入第一線治療，需要與 PD-1 抑制劑合併使用並取得成功。顯然，我們還沒有看到你們開始進行關鍵性資料集的研究，而且你們剛才也說，確定治療方案可能需要更長時間。或者，你們也可以選擇 SHIP2 研究計畫。首先，你們能否給我們公佈 SHIP2 聯合治療數據的時間表？其次，除了上述方案之外，還有沒有其他途徑可以讓 sotorasib 進入第一線肺癌治療？我們這次電話會議可能沒有考慮到這一點。

Yes. Thanks, Dane. In terms of potential frontline combinations, I think a number of them that are being examined in the master protocol, if we can enhance efficacy by multiple hits on the pathway could be feasible, for example, the MEK combination, the EGFR inhibitor combinations. And then as well, as you mentioned, PD-1, whether that is in combination or sequentially, for example, to rely on the priming effect is a question that we're trying to answer.

是的，謝謝，Dane。關於潛在的第一線聯合療法，我認為主方案中正在研究的一些方案，如果我們能透過多次靶向同一通路來提高療效，可能是可行的，例如MEK抑製劑聯合療法和EGFR抑製劑聯合療法。此外，正如您所提到的，PD-1抑制劑，無論是聯合用藥還是序貫用藥，能否利用其啟動效應，也是我們正在努力解答的問題。

SHIP2, I would also consider an additional hit on the pathway and would also fall into that grouping. So I think we'll be guided by emerging data, but all of those would be potential avenues into earlier lines of therapy, in addition, also potentially avenues into other indications such as colorectal cancer and some of the other solid tumors where G12C mutations occur.

SHIP2，我認為它也是該通路上的另一個靶點，也應該歸入這一類。所以我覺得我們會根據新出現的數據來判斷，但所有這些都可能成為早期治療的途徑，此外，也可能成為治療其他適應症的途徑，例如結直腸癌和其他一些存在G12C突變的實體瘤。

Your next question is from Ronny Gal with Bernstein.

下一個問題來自伯恩斯坦的羅尼·加爾。

Three, if I may. First, just the traditional sotorasib question. I guess we saw some data in AACR about patients having multiple escape mutations from the first -- from being -- when treated with a KRAS G12C inhibitor. And I was wondering, does that concern you that patient escape so quickly with multiple mechanisms? Does that suggest that maybe 2 agents will not be enough? Or is that kind of par for the course, and this is what was expected?

第三個問題，如果可以的話。首先，我想問一個關於索托拉西布的傳統問題。我猜我們在AACR會議上看到一些數據，顯示有些患者在使用KRAS G12C抑制劑治療後，出現了多種逃脫突變。我想知道，患者如此迅速地出現多種逃脫機制，您是否對此感到擔憂？這是否意味著兩種藥物可能不足以治療？還是這其實是正常現象，也在預期之中？

And second, we have seen some of your peers license China-developed and tested product to bring to the developed market, especially in oncology. And I was wondering if you consider the strategy, especially as a biosimilar player. This seems to be a natural complementary strategy. And if so, whether you come out with -- on that?

其次，我們看到一些同業將中國研發並經過驗證的產品授權引進已開發市場，尤其是在腫瘤領域。我想知道您是否考慮過這種策略，特別是作為生物類似藥企業。這似乎是一種天然的互補策略。如果是的話，您對此有何看法？

And maybe I'll start with the first part, and then have Murdo address the second part. Yes, in terms of the mutational patterns that were recently reported, I would say that, biologically, nothing that we saw surprised us based on everything we've learned about these pathways in the last 30 to 40 years and the potential mechanisms of resistance. This also points the way, I think, to specific combinations that may, in fact, help to ameliorate those resistance patterns.

或許我可以先講第一部分，然後讓默多來談談第二部分。是的，就最近報導的突變模式而言，從生物學角度來看，基於過去三、四十年我們對這些通路以及潛在抗藥性機制的了解，我們所看到的並沒有讓我們感到驚訝。我認為這也為尋找可能有助於改善這些抗藥性模式的特定組合指明了方向。

I will point out that we will be presenting in short order here also updated comprehensive biomarker data, including mutational data. And I think you'll find that of interest, and that is certainly helping to guide our own thinking about the development program as well.

我還要指出，我們稍後將在此展示更新的綜合生物標記數據，包括突變數據。我相信您會對此感興趣，而這些數據也確實有助於我們思考研發方案。

Murdo, do you want to take the second half of the question?

默多，你想回答問題的後半部嗎？

Yes, Ronny. We continue to look globally for product opportunities to license and promote in the world. And I think in oncology, in particular, there have been some interesting deals done lately. We obviously have a strong partnership already with a company based in China through BeiGene, and we continue to enjoy that partnership and the co-development that we have.

是的，羅尼。我們一直在全球範圍內尋找產品授權和推廣的機會。我認為，尤其是在腫瘤領域，最近達成了一些很有趣的交易。我們顯然已經透過百濟神州與一家中國公司建立了牢固的合作關係，我們很享受這種合作關係以及我們共同開展的研發工作。

I would also say that given our global footprint, Amgen really is an excellent partner of choice with our global capabilities in oncology and general medicine. So we're open to do business with Chinese companies, Japanese companies, global companies. Absolutely.

我還想說，鑑於我們的全球佈局，安進憑藉其在腫瘤學和普通醫學領域的全球實力，確實是理想的合作夥伴。因此，我們樂於與中國公司、日本公司以及全球性公司開展業務。絕對是如此。

Our next question is from Carter Gould with Barclays.

下一個問題來自巴克萊銀行的卡特·古爾德。

Maybe just switching gears a bit and moving to BCMA. It sounds like you're about to go back into the clinic. Can you maybe just give us some color on sort of the changes to the protocol or dose escalation? Any read-through to the broader platform? And just, I guess, focus more specifically on BCMA, with those changes, comment on sort of your competitiveness in a increasingly competitive space.

或許我們可以稍微轉換一下話題，聊聊BCMA。聽起來您好像要重返臨床了。您能否簡單介紹一下方案或劑量遞增方面的變化？這些變化對整個治療平台有何影響？另外，我想更具體地談談BCMA，在這些變化之後，您如何看待在競爭日益激烈的領域中保持競爭力。

Yes, Carter, thanks for the question. So we do expect to begin dosing again, hopefully, in the next few weeks or so. As you intuited, this would adjust some of the intra-patient dose escalation that is typical with the use of BiTE molecules. And so that -- we'll be pushing that forward.

是的，卡特，謝謝你的提問。我們預計在接下來的幾週內恢復給藥。正如你所料，這將調整使用BiTE分子時常見的患者體內劑量遞增問題。因此，我們會推進這項工作。

More broadly, obviously, we want to be able to deliver a program here that can offer something to patients and physicians that they otherwise might not have. And we'll continually assess the program against that metric.

更廣泛地說，顯然，我們希望在這裡提供一個能夠為患者和醫生提供他們原本可能無法獲得的東西的項目。我們將持續根據此標準評估該項目。

More broadly, I'm quite pleased with the progress we made on AMG 160 and AMG 757. And as always, we'd always provide a cautionary note about extrapolating extensively across programs because much of what we witnessed in the clinic is target-dependent. And so all of these programs will have their idiosyncrasies that need to be worked through as part of the development program.

總的來說，我對AMG 160和AMG 757的研發進度相當滿意。但一如既往，我們始終提醒大家，不應輕易將不同項目的結果進行大規模推斷，因為我們在臨床試驗中觀察到的許多現像都與目標車型有關。因此，所有這些項目都會有其自身的特殊性，需要在研發過程中加以解決。

Your next question is from Colin Bristow with UBS Equities.

下一個問題來自瑞銀股票部的 Colin Bristow。

Just a quick update from you guys on the business development priorities. What are your current areas of interest? How are you thinking about deal size? And just an overall, I guess, commentary on how you're thinking about valuations in the space.

請各位簡要報告一下業務拓展的重點。你們目前關注的領域有哪些？你們如何考慮交易規模？另外，能否就該領域的估值問題談談你們的看法？

Well, Colin, as you know, we transacted 2 acquisitions in the first quarter, one at the preclinical stage, one at the Phase III ready. And I think that reflects the breadth of interest that we have. We're continuing to look at acquisitions and licensing opportunities in our stated areas of focus. So in particular, immunology, the inflammatory diseases, cardiovascular diseases, cancer are attractive to us. And then we have very strong franchises and a few other therapeutic areas, as you know, in migraine and bone health and nephrology. So we look for commercial opportunities there as well.

科林，如你所知，我們在第一季度完成了兩項收購，一項處於臨床前階段，另一項已準備進入第三期臨床試驗。我認為這反映了我們廣泛的投資興趣。我們將繼續在我們既定的重點領域尋找收購和授權機會。特別是免疫學、發炎性疾病、心血管疾病和癌症領域，這些領域對我們來說都很有吸引力。此外，如你所知，我們在偏頭痛、骨骼健康和腎臟病等其他一些治療領域也擁有非常強大的產品線。因此，我們也在這些領域尋找商業機會。

That's helpful. Maybe just one quick question. In terms of protein degradation, obviously, you have a platform that's somewhat early. Just any interest in expanding your positioning in that space?

這很有幫助。或許我可以問一個問題。就蛋白質降解而言，顯然你們的平台還處於起步階段。你們是否有意拓展在該領域的業務？

Yes. As we've said before, I think going forward, we would expect the development of what we call the induced proximity platform to depend both on internal innovation and external partnerships and potentially acquisitions. So we're open to both. We're making a lot of progress there, and we'll provide more detail a bit later.

是的。正如我們之前所說，我認為展望未來，我們所謂的「誘導近距離平台」的發展將依賴內部創新、外部合作以及可能的收購。所以我們對兩者都持開放態度。我們在這方面取得了很大進展，稍後會提供更多細節。

Your next question is from Robyn Karnauskas with Truist.

下一個問題來自 Truist 的 Robyn Karnauskas。

So you addressed a little bit of the moderate to severe pressure on the competition for Otezla. Could you again address a little bit more now that we have more granular data from sotorasib and others on the topicals? Do you think the topicals being cheaper might push out some of the uptick in the biologics for Otezla?

您剛才談到了Otezla面臨的中度至重度競爭壓力。現在我們有了sotorasib和其他外用藥物的更詳細的數據，您能否再詳細談談這個問題？您認為外用藥物價格較低是否會抑制Otezla生物製劑價格的上漲？

And then if you want to answer that one, just throwing out here. You're one of the first to do RTOR application for oncology with all the FDA controversy development. Can you just tell us like how that's going? Is it proceeding as normal? And we're all wondering how that application process will go because that could be the faster way to market for a lot of new drugs.

如果您想回答這個問題，我就先拋磚引玉一下。您是首批在FDA爭議不斷的背景下申請RTOR用於腫瘤治療的機構之一。您能告訴我們目前的進展嗎？一切是否正常？我們都很想知道這個申請流程會如何發展，因為這可能是許多新藥更快上市的途徑。

I'll try to get them both quickly.

我會盡快把它們都弄到手。

All right. Robyn, look, we think that there's obviously a role for topicals to play for patients with low body surface area involvement of their disease. When it starts to become a broader surface area or in awkward places on the patient's body, then they're looking for a systemic agent, and they're looking for a safe and effective one. And that's really where we think the mild to moderate opportunity is for Otezla.

好的。 Robyn，你看，我們認為對於體表面積較小的患者來說，局部用藥顯然可以發揮作用。但當病情開始擴散到更大範圍，或出現在患者身體的敏感部位時，他們就需要全身用藥，而且是安全有效的藥物。我們認為，這正是Otezla在輕度至中度患者治療的優勢所在。

And we -- we're not even considering the millions of patients out there with mild to moderate. We're looking at about a 40% to 50% addressable patient population. So we're giving at least half the market as a topical market, assuming the other half would be addressable with an oral. Dave?

而且我們——我們甚至還沒考慮到數百萬輕度至中度患者。我們估計只有大約40%到50%的患者群體屬於潛在目標族群。所以我們至少把一半的市場定位為外用藥市場，假設另一半可以用口服藥來解決。戴夫？

Yes. And in terms of RTOR, or real-time oncology review, what that does is permit submission of tranches of data as you move through the submission process as opposed to waiting and submitting either a complete file all at once or very large chunks of a file. We've had very productive interactions with the FDA. And in our view, RTOR process has worked quite nicely here. In the longer term, quite frankly, I think that this is the way of the future, not only in oncology, but across therapeutic areas for more real-time submission of data probably from the inception of development programs.

是的。就即時腫瘤學審查（RTOR）而言，它允許在提交流程中分批提交數據，而不是像以前那樣一次性提交整個文件或提交非常大的數據塊。我們與FDA的溝通非常富有成效。我們認為，RTOR流程在這裡運作得相當不錯。坦白說，從長遠來看，我認為這是未來的發展方向，不僅適用於腫瘤學，也適用於其他治療領域，從研發計畫開始就應該實現更即時的數據提交。

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

下一個問題來自加拿大皇家銀行資本市場的 Kennen MacKay。

Question on tezepelumab. We've recently heard from a KOL some thoughts that this actually could be as competitive as some of the other biologics in asthma in the high eosinophil group, not just competitive in the high unmet need for low eosinophil market. Just wondering when that data does come out -- that full publication does come out, really, what we should be looking for in these high eosinophil patients for signs of competitiveness there.

關於tezepelumab的問題。我們最近從一位關鍵意見領袖那裡了解到，這種藥物在嗜酸性粒細胞增多症哮喘患者群體中，其競爭力可能與其他一些生物製劑不相上下，而不僅僅是在嗜酸性粒細胞減少症哮喘患者這個尚未滿足的巨大需求領域。我想知道，當相關數據——確切地說是完整的研究報告——公佈後，我們應該關注哪些指標來判斷這種藥物在嗜酸性粒細胞增多症氣喘患者群體中的競爭力。

Yes. No. Thanks, Kennen. As we've reported, as you saw, and we'll be providing some data updates, additional analyses on the NAVIGATOR Phase III trial at the American Thoracic Society meeting in a few weeks now. Across the board, we saw efficacy that we think is consistent with first-line use. It's important to understand that there are many patients with severe uncontrolled asthma who have disease that is seeking another treatment right now, meaning they are not controlled with currently available therapies.

是的。不。謝謝，肯南。正如我們之前所報導的，也正如您所看到的，我們將在幾週後的美國胸腔科協會會議上提供一些關於NAVIGATOR III期試驗的數據更新和補充分析。整體而言，我們觀察到的療效與第一線治療方案一致。需要注意的是，目前有許多重度未控制氣喘患者正在尋求其他治療方案，這意味著他們目前的治療方案無法控制病情。

And so regardless of eosinophil count, we think that the clinical profile of this molecule is quite attractive. And my view continues to be that this is just going to be a really important medicine in asthma for patients.

因此，無論嗜酸性粒細胞計數如何，我們都認為這種分子的臨床特性非常吸引人。我仍然認為，對於氣喘患者來說，這將會是一種非常重要的藥物。

Your final question comes from Cory Kasimov with JPMorgan.

最後一個問題來自摩根大通的科里·卡西莫夫。

Updated LUMAKRAS' ability to penetrate the blood brain barrier, and do you see this as a potential future source of differentiation one way or the other in the KRAS field?

LUMAKRAS 基因更新後能夠穿透血腦屏障，您認為這是否會成為 KRAS 領域未來發展的潛在方向？

Yes. Cory, thanks. Quickly. So we are actually studying specifically LUMAKRAS in patients with brain metastases. I think the clinical data will be definitive here. And once we've amassed a large enough data set, we'll present that. But it's full speed ahead to answer that question.

是的，科里，謝謝。很快。我們目前正在專門研究腦轉移患者中的LUMAKRAS基因。我認為臨床數據將給出明確結論。一旦我們收集到足夠大的資料集，就會公佈結果。但我們現在正全力以赴地解答這個問題。

Okay. Well, thank you all for your patience and for dialing into the call today. I'll remind you, as always, that Arvind and his team will be around for several hours still if you have other questions that you didn't get answered. But we appreciate your support and look forward to being back with you in July. Thanks.

好的。非常感謝大家的耐心等待，也感謝大家今天撥入電話會議。我還是要提醒大家，如果您還有其他問題沒有得到解答，Arvind 和他的團隊還會在線幾個小時。我們非常感謝大家的支持，期待七月再次與大家見面。謝謝。

Thank you, everybody.

謝謝大家。

This concludes Amgen's First Quarter 2021 Financial Results Conference Call. You may now disconnect.

安進公司2021財年第一季財務業績電話會議到此結束。您可以斷開連線了。