禮來公司 (LLY) 2021 Q1 法說會逐字稿

Ladies and gentlemen, thank you for standing by, and welcome to the Lilly Q1 2021 Earnings Conference Call. (Operator Instructions) As a reminder, this conference is being recorded.

女士們，先生們，感謝您的支持，歡迎參加禮來公司 2021 年第一季度收益電話會議。 （操作員說明）作為提醒，本次會議正在錄製中。

I would now like to turn the conference over to our host, Mr. Kevin Hern. Please go ahead.

我現在想將會議轉交給我們的主持人 Kevin Hern 先生。請繼續。

Good morning. Thank you for joining us for Eli Lilly and Company's Q1 2021 Earnings Call. I'm Kevin Hern, Vice President of Investor Relations. Joining me on today's call are Dave Ricks, Lilly's Chairman and CEO; Anat Ashkenazi, Chief Financial Officer; Dan Skovronsky, Chief Scientific Officer; Anne White, President of Lilly Oncology; Ilya Yuffa, President of Lilly Bio-Medicines; Mike Mason, President of Lilly Diabetes. And we'd also like to welcome Jake Van Naarden, CEO of Loxo Oncology at Lilly, who will be joining us today and moving forward to answer your questions about discovery and early-stage oncology efforts he's leading. Now I'll turn the call over to Dave -- sorry, we're also joined by Sara Smith and Lauren Zierke of the Investor Relations team.

早上好。感謝您參加禮來公司 2021 年第一季度財報電話會議。我是投資者關係副總裁 Kevin Hern。與我一起參加今天電話會議的還有禮來公司董事長兼首席執行官戴夫·里克斯（Dave Ricks）； Anat Ashkenazi，首席財務官； Dan Skovronsky，首席科學官；禮來腫瘤學總裁 Anne White； Ilya Yuffa，禮來生物醫藥總裁；禮來糖尿病公司總裁邁克·梅森。我們還要歡迎禮來公司 Loxo 腫瘤學首席執行官 Jake Van Naarden，他今天將加入我們並繼續回答您關於他領導的發現和早期腫瘤學工作的問題。現在我將把電話轉給戴夫——抱歉，投資者關係團隊的 Sara Smith 和 Lauren Zierke 也加入了我們的行列。

During this conference call, we anticipate making projections and forward-looking statements based on our current expectations. Our actual results could differ materially due to a number of factors, including those listed on Slide 3. Additional information concerning factors that could cause actual results to differ materially is contained in our latest Forms 10-K and subsequent Forms 10-Q and 8-K filed with the Securities and Exchange Commission. The information we provide about our products and pipeline is for the benefit of the investment community. It is not intended to be promotional and is not sufficient for prescribing decisions. As we transition to our prepared remarks, a reminder that our commentary will focus on non-GAAP financial measures.

在這次電話會議期間，我們預計會根據我們目前的預期做出預測和前瞻性陳述。由於多種因素，包括幻燈片 3 中列出的因素，我們的實際結果可能存在重大差異。有關可能導致實際結果存在重大差異的因素的其他信息包含在我們最新的表格 10-K 和後續表格 10-Q 和 8-中K 向證券交易委員會提交了申請。我們提供的有關我們的產品和管道的信息是為了投資界的利益。它不是為了促銷，也不足以做出處方決定。當我們過渡到我們準備好的評論時，提醒我們的評論將集中在非公認會計準則財務指標上。

Now I'll turn the call over to Dave for a summary of our results from the first quarter of 2021.

現在，我將把電話轉給戴夫，以總結我們 2021 年第一季度的業績。

Okay. Thanks, Kevin. Lilly entered 2021 focused on expanding our reach to over 45 million patients by scaling our key growth brands around the world, continuing the advancement of our pipeline following a very successful 2020 and increasing productivity in the SG&A line while investing in research for sustainable long-term growth. We are pleased with the progress we've made on these objectives in our first quarter while also delivering hundreds of thousands of doses of our COVID-19 antibodies to patients to help the continued fight against COVID-19. As we unpack this quarter's results, we will attempt to give you a clear picture of the underlying trends in our core business.

好的。謝謝，凱文。禮來進入 2021 年，專注於通過擴大我們在全球的主要增長品牌，在 2020 年非常成功後繼續推進我們的管道，提高 SG&A 線的生產力，同時投資於可持續長期研究生長。我們對第一季度在這些目標上取得的進展感到高興，同時還向患者提供了數十萬劑 COVID-19 抗體，以幫助繼續對抗 COVID-19。在我們解讀本季度的業績時，我們將嘗試讓您清楚地了解我們核心業務的潛在趨勢。

We recognize this quarter was noisy, catching the increased consumer stock in from the Q1 2020 in our quarterly compare and increased COVID-19 therapy R&D spend in 2021. These items, coupled with the FX rate movement and a number of changes to U.S. government purchase agreements for COVID-19 antibodies throughout the quarter, make for a longer earnings call and press release. And we realize, for those keeping score on sell-side model accuracy, perhaps some disappointment. Nonetheless, underneath all of that is a strong and growing core business for Lilly and a significant number of positive, even compelling pipeline readouts in the quarter to support long-term growth across all of our core therapy areas. And we continue to expect top line growth and margin expansion to accelerate throughout this year.

我們認識到本季度很嘈雜，在我們的季度比較中從 2020 年第一季度開始增加了消費者庫存，並在 2021 年增加了 COVID-19 治療研發支出。這些項目，再加上匯率變動和美國政府採購的一些變化整個季度的 COVID-19 抗體協議，使得財報電話會議和新聞稿的時間更長。我們意識到，對於那些在賣方模型準確性上得分的人來說，也許有些失望。儘管如此，在這一切的背後，是禮來（Lilly）強大且不斷增長的核心業務，以及本季度大量積極、甚至令人信服的管道數據，以支持我們所有核心治療領域的長期增長。我們繼續預計今年全年收入增長和利潤率擴張將加速。

This quarter, revenue grew 16% compared to Q1 2020 or 13% in constant currency. This performance was driven entirely by volume, which grew 17 percentage points. As previously highlighted in Q1 2020, we had roughly a $250 million COVID-19-related inventory build that is impacting the year-over-year comparison. When excluding COVID-19 antibody revenue and the Q1 2020 stocking benefit, our core business grew 7% for the quarter. Key growth products continued to drive volume and revenue growth and now represent 52% of our core business in Q1 2021.

本季度，收入與 2020 年第一季度相比增長 16%，按固定匯率計算增長 13%。這一表現完全由銷量推動，銷量增長了 17 個百分點。正如之前在 2020 年第一季度所強調的那樣，我們有大約 2.5 億美元的 COVID-19 相關庫存構建，這正在影響同比比較。排除 COVID-19 抗體收入和 2020 年第一季度庫存收益後，我們的核心業務在本季度增長了 7%。關鍵增長產品繼續推動銷量和收入增長，目前占我們 2021 年第一季度核心業務的 52%。

Our non-GAAP gross margin was 75.4% in Q1 and 78% excluding the impact of foreign exchange on international inventories sold. Our non-GAAP operating margin was 27.5% for the quarter and 30.1% excluding the FX impact. While foreign exchange on international inventories sold has a modest effect on our Q1 -- on our results in 2019 and 2020, in the first quarter of 2021, we experienced over 250 basis point of negative impact on our gross margin and operating margin. Recall that is purely a noncash accounting item.

我們第一季度的非美國通用會計準則毛利率為 75.4%，不包括外匯對已售國際庫存的影響為 78%。我們本季度的非公認會計原則營業利潤率為 27.5%，不包括外匯影響為 30.1%。儘管已售國際庫存的外匯對我們的第一季度影響不大——對我們 2019 年和 2020 年的業績，但在 2021 年第一季度，我們的毛利率和營業利潤率受到了超過 250 個基點的負面影響。回想一下，這純粹是一個非現金會計項目。

On the pipeline front, we achieved multiple milestones since our Q4 earnings call, including the Phase III initiation of pirtobrutinib, formerly known as LOXO-305; and for additional obesity studies in tirzepatide's SURMOUNT program; the FDA granted Emergency Use Authorization for the administration of bamlanivimab and etesevimab together as a treatment for COVID-19; positive Phase III results from tirzepatide's SURPASS-2, 3 and 5 trials in type 2 diabetes; and positive Phase III results for mirikizumab in ulcerative colitis and baricitinib in alopecia areata.

在管道方面，自第四季度財報電話會議以來，我們實現了多個里程碑，包括 pirtobrutinib（以前稱為 LOXO-305）的 III 期啟動；以及在 tirzepatide 的 SURMOUNT 計劃中進行額外的肥胖研究； FDA 授予緊急使用授權，將 bamlanivimab 和 etesevimab 一起用於治療 COVID-19； tirzepatide 在 2 型糖尿病中的 SURPASS-2、3 和 5 試驗的 III 期陽性結果； mirikizumab 治療潰瘍性結腸炎和 baricitinib 治療斑禿的 III 期陽性結果。

About a decade ago, Lilly made the decision to enter into and invest in immunology with the Phase III initiation of ixekizumab, now known as Taltz. Since then, we have added Olumiant in rheumatoid arthritis and several new indications with first or best-in-category data for Taltz and Olumiant in rheumatology and dermatology. This year, we see further expansion of our immunology strategy with the successful completion of Phase III studies of mirikizumab in ulcerative colitis. The first IL-23p19 antibody medicine to demonstrate results in this setting.

大約十年前，禮來（Lilly）決定進入並投資免疫學，並啟動了 ixekizumab 的 III 期，現在稱為 Taltz。從那時起，我們在類風濕性關節炎中添加了 Olumiant，並在風濕病學和皮膚病學中添加了 Taltz 和 Olumiant 的幾個新適應症，這些適應症具有第一或最佳類別數據。今年，隨著 mirikizumab 治療潰瘍性結腸炎的 III 期研究的成功完成，我們看到我們的免疫學戰略進一步擴展。第一個在這種情況下證明結果的 IL-23p19 抗體藥物。

We're also excited about lebrikizumab's potential to differentiate from Dupixent on itch, sleep and safety, primarily in conjunctivitis, in what is an increasingly large and growing class with meaningful unmet medical need. And we anticipate multiple Phase III readouts for lebrikizumab later this year in monotherapy and in combination with corticosteroids. We look forward to potentially reaching increasing numbers of patients in difficult-to-treat immunology conditions in the coming years.

我們也對 lebrikizumab 在瘙癢、睡眠和安全性（主要是結膜炎）方面與 Dupixent 區分開來的潛力感到興奮，這是一個日益龐大且不斷增長的類別，具有有意義的未滿足的醫療需求。我們預計今年晚些時候會在單藥治療和與皮質類固醇聯合治療中對 lebrikizumab 進行多個 III 期讀數。我們期待在未來幾年內有可能接觸到越來越多患有難以治療的免疫疾病的患者。

We also entered into several business development deals, including the in-licensing of a RIPK1 inhibitor from Rigel Pharmaceuticals and the divestiture of QBREXZA, which along with lebrikizumab was part of the Dermira acquisition last year. We also distributed nearly $800 million in dividends this quarter with the share -- dividend per share increasing 15% versus last year.

我們還達成了幾項業務開發交易，包括從 Rigel Pharmaceuticals 獲得 RIPK1抑製劑的許可以及剝離 QBREXZA，後者與 lebrikizumab 一起是去年收購 Dermira 的一部分。本季度我們還派發了近 8 億美元的股息，每股股息比去年增長了 15%。

Moving on to Slides 5 and 6, you'll see a list of key events since our last earnings call. We announced plans to host a webinar to provide an overview of the company's commitment in the areas of environmental, social and governance for the investment community, for media and the general public on May 4, 2021. Additionally, we announced 2 planned retirements of long-tenured executives and several additions to our leadership team. I'd like to thank Myles O'Neill, President of Lilly Manufacturing; and Melissa Barnes, our Chief Ethics and Compliance Officer, for their leadership and service to our company. We also extend a warm welcome to Edgardo Hernandez, who will be succeeding Myles; to Alonzo Weems, who will succeed Melissa; and to Diogo Rau, who will be joining Lilly next month as Chief Information and Digital Officer, succeeding Aarti Shah, whose retirement was announced last fall.

轉到幻燈片 5 和 6，您將看到自我們上次財報電話會議以來的關鍵事件列表。我們宣布計劃於 2021 年 5 月 4 日舉辦一次網絡研討會，概述公司在環境、社會和治理領域為投資界、媒體和公眾所做的承諾。此外，我們還宣布了 2 次長期退休計劃- 終身高管和我們領導團隊的幾位新成員。我要感謝禮來公司總裁 Myles O'Neill；以及我們的首席道德與合規官 Melissa Barnes，以表彰他們對我們公司的領導和服務。我們也熱烈歡迎將接替邁爾斯的 Edgardo Hernandez；給將接替梅麗莎的阿朗佐·威姆斯；以及 Diogo Rau，他將於下個月加入禮來擔任首席信息和數字官，接替去年秋天宣布退休的 Aarti Shah。

Finally, we announced the appointment of Anat Ashkenazi, our CFO. Anat has a deep experience, having been the CFO of every part of our value chain. For the last 4 years, Anat has a large -- has led a large portion of our finance organization with all of our divisional CFOs reporting to her as well as our accounting and financial reporting team, our corporate strategy group and our business transformation office. During this time, Anat worked closely with me, our Executive Committee and our Board of Directors to develop and implement our annual business and long-term strategic plans. I have no doubt that Anat will perform extremely well as CFO of Lilly and expect no changes in our priorities, our strategy or execution, given her significant involvement in all those areas.

最後，我們宣布任命我們的首席財務官 Anat Ashkenazi。 Anat 擁有豐富的經驗，曾擔任我們價值鏈各個環節的首席財務官。在過去的 4 年裡，Anat 領導了我們財務組織的大部分工作，我們所有的部門 CFO 以及我們的會計和財務報告團隊、我們的企業戰略團隊和我們的業務轉型辦公室都向她匯報。在此期間，Anat 與我、我們的執行委員會和董事會密切合作，共同製定和實施我們的年度業務和長期戰略計劃。毫無疑問，Anat 作為禮來公司的首席財務官將表現出色，並且鑑於她在所有這些領域的重要參與，預計我們的優先事項、戰略或執行不會發生變化。

Anat, welcome to our leadership team, and I'll turn the call over to you for our Q1 results.

Anat，歡迎加入我們的領導團隊，我會將電話轉給您了解我們的第一季度業績。

Thanks, Dave. Slide 7 summarizes our non-GAAP financial performance in the first quarter. As Dave mentioned, revenue increased 16% this quarter compared to Q1 of 2020 or 7% when excluding the COVID-19 antibody revenue and the Q1 2020 COVID-related stocking benefit, representing a good momentum for our core business.

謝謝，戴夫。幻燈片 7 總結了我們在第一季度的非公認會計原則財務業績。正如 Dave 所提到的，本季度的收入與 2020 年第一季度相比增長了 16%，如果不包括 COVID-19 抗體收入和 2020 年第一季度與 COVID 相關的庫存收益，則增長了 7%，這代表了我們核心業務的良好勢頭。

Last year, with the health and safety of our employees, patients and providers in mind, we shifted from in-person interactions to primarily virtual interactions and began 2021 with few sales reps in the field in the U.S. We feel good about our capabilities to work with providers virtually and are encouraged as we exited Q1 2021 with the majority of U.S. reps back in the field. As we navigate the early stages of the recovery, we're focused on operational excellence in both virtual and in-person environment and are pleased with the volume and share growth in key brands despite continued pandemic-related headwinds for several classes.

去年，考慮到我們員工、患者和提供者的健康和安全，我們從面對面的互動轉變為主要的虛擬互動，並從 2021 年開始，在美國幾乎沒有銷售代表。我們對自己的工作能力感到滿意虛擬地與供應商合作，並在我們退出 2021 年第一季度時受到鼓勵，大多數美國代表回到了現場。在我們度過復甦的早期階段時，我們專注於虛擬和麵對面環境中的卓越運營，並且對主要品牌的銷量和份額增長感到滿意，儘管幾個班級持續面臨與大流行相關的逆風。

As we look at gross margin, gross margin as a percent of revenue declined 490 basis points to 75.4%. Excluding the impact of foreign exchange on international inventory sold, gross margin as a percent of revenue was 78%, a decrease of 260 basis points, primarily due to the unfavorable product mix driven largely by sales of COVID-19 antibodies and, to a lesser extent, by lower realized prices and revenue.

當我們查看毛利率時，毛利率佔收入的百分比下降了 490 個基點至 75.4%。排除外匯對銷售的國際庫存的影響，毛利率佔收入的百分比為 78%，下降了 260 個基點，主要是由於主要受 COVID-19 抗體銷售驅動的不利產品組合，以及較小的在某種程度上，通過降低實現的價格和收入。

Moving down the P&L. Operating expenses grew 11% compared to the same quarter last year. Marketing, selling and administrative expenses increased 2% while R&D expenses increased 21%, driven primarily by $220 million of investments in COVID-19 therapies. Net of the COVID-19 expenses, R&D increased 5%, driven by continued investments in our late-stage pipeline.

向下移動損益表。與去年同期相比，運營費用增長了 11%。營銷、銷售和管理費用增長 2%，而研發費用增長 21%，主要受 COVID-19 療法投資 2.2 億美元的推動。扣除 COVID-19 費用後，由於對後期管道的持續投資，研發增長了 5%。

Total operating expense growth was less than 3% compared to Q1 2020 when excluding the investments in COVID-19 therapies. Operating income increased 6% compared to Q1 of 2020 and operating income as a percent of revenue was 27.5% for the quarter, a decline of 250 basis points compared to prior year. This decline was driven entirely by the impact of foreign exchange on international inventories sold.

排除對 COVID-19 療法的投資後，與 2020 年第一季度相比，總運營費用增長不到 3%。與 2020 年第一季度相比，營業收入增長了 6%，本季度營業收入佔收入的百分比為 27.5%，與去年同期相比下降了 250 個基點。這種下降完全是由於外匯對國際銷售庫存的影響。

Other income and expense was income of $35 million this quarter compared to expense of $73 million in Q1 of 2020, driven primarily by a benefit related to favorable European patent settlement for Alimta. As we noted previously, beginning in 2021, we are excluding the gains or losses due to equity investments from our non-GAAP measures and have provided revised figures for 2020 in our investor workbook to enable year-over-year comparison on that same basis.

其他收入和支出為本季度的收入為 3500 萬美元，而 2020 年第一季度的支出為 7300 萬美元，這主要得益於與 Alimta 的有利歐洲專利和解相關的收益。正如我們之前提到的，從 2021 年開始，我們將非公認會計原則措施中的股權投資收益或損失排除在外，並在我們的投資者手冊中提供了 2020 年的修訂數據，以便在相同的基礎上進行同比比較。

Our effective tax rate was 10.8%, a decrease of 210 basis points compared with the same quarter last year. The effective tax rate for both periods was reduced by net discrete tax benefits with the larger net discrete benefit reflected in the first quarter of 2021. At the bottom line, net income and earnings per share increased 16%.

我們的有效稅率為 10.8%，與去年同期相比下降了 210 個基點。兩個時期的有效稅率因淨離散稅收優惠而降低，2021 年第一季度反映的淨離散利益更大。最終，淨收入和每股收益增長了 16%。

On Slide 8, we quantify the effect of price, rate and volume on revenue growth across the world. U.S. revenue grew 18% compared to the first quarter of 2020 while revenue decreased slightly, excluding COVID-19 antibodies. Adjusting for the Q1 2020 stocking benefit, the core business grew 5% in the U.S. These results were driven entirely by volume, led by Trulicity and Taltz, partially offset by a mid-single-digit price decline.

在幻燈片 8 中，我們量化了價格、費率和數量對全球收入增長的影響。與 2020 年第一季度相比，美國收入增長了 18%，而收入略有下降，不包括 COVID-19 抗體。調整 2020 年第一季度的庫存收益後，美國的核心業務增長了 5%。這些結果完全由銷量推動，由 Trulicity 和 Taltz 引領，部分被中個位數的價格下跌所抵消。

Pricing was a 6% drag on U.S. revenue growth this quarter, driven primarily by Taltz' improved access and corresponding higher contracted rates, partially offset by a modest list price increase. Excluding the impact of Taltz' win at ESI, we experienced low single-digit net price decline in the U.S. in the first quarter of 2021. We noted on previous calls that we expect that Taltz would experience price headwind in Q1 beyond general rate pressure with the improved access position.

定價對本季度美國收入增長造成了 6% 的拖累，這主要是由於 Taltz 改善了准入和相應的更高的合同費率，部分被適度的標價上漲所抵消。排除 Taltz 在 ESI 獲勝的影響，我們在 2021 年第一季度在美國經歷了低個位數的淨價格下跌。我們在之前的電話會議中註意到，我們預計 Taltz 在第一季度將遇到價格逆風，超過一般利率壓力改善的訪問位置。

There were 2 pieces of the ESI impact. The first existing patients already covered through medical exceptions were moved to the newly contracted rate, a onetime step-down in prices as we move through 2021. In addition, we were pleased with the update for new patients at ESI at the contracted rate and we expect that, that population will grow meaningfully over time.

有 2 個 ESI 影響。已經通過醫療例外覆蓋的第一批現有患者被轉移到新合同費率，隨著我們進入 2021 年，價格將一次性降低。此外，我們對 ESI 新患者按合同費率進行的更新感到滿意，我們預計隨著時間的推移，人口將顯著增長。

There is always a near-term impact when we have a step -- a significant step-up in access. And this win nearly doubled our commercial access. We're encouraged by the volume growth we saw in the first quarter and believe Taltz will return to net sales growth in the second quarter, which should continue to accelerate as we move through the year as the volume growth from the major access upgrade outpaces the related pricing headwind.

當我們邁出一步時，總會產生近期的影響——訪問量的顯著提升。這場胜利幾乎使我們的商業訪問量翻了一番。我們對第一季度看到的銷量增長感到鼓舞，並相信 Taltz 將在第二季度恢復淨銷售額增長，隨著主要訪問升級的銷量增長超過相關的定價逆風。

Beyond Taltz, segment mix was not a major of U.S. price performance in the first quarter as increased utilization in the more highly rebated government segment was offset by lower utilization in the 340B segment, primarily for our diabetes portfolio. While mid-term trends are stable at present, given the increase in variability in payer mix, we continue to expect quarterly variability in reported net price changes. We also expect Taltz' price impact to moderate as we move through the year and overall, low to mid-single-digit total net price decline in the U.S. for the full year.

除了 Taltz 之外，細分市場組合併不是第一季度美國價格表現的主要因素，因為高回扣政府細分市場的利用率增加被 340B 細分市場的較低利用率抵消，主要用於我們的糖尿病產品組合。儘管目前中期趨勢穩定，但鑑於支付者組合的可變性增加，我們繼續預計報告的淨價格變化將出現季度波動。我們還預計 Taltz 的價格影響會隨著我們全年的發展而放緩，總體而言，美國全年總淨價格將出現低至中個位數的下降。

Moving to Europe. Revenue grew 15% in constant currency. Excluding COVID-19 antibody revenue and the impact of Q1 2020 COVID-related stocking, revenue grew 5% in constant currency despite lockdowns in a number of European countries and driven primarily -- entirely by volume growth for Alimta, Trulicity and Taltz. We're pleased with the momentum of our business in Europe and are looking forward to continued strong growth in 2021.

搬到歐洲。按固定匯率計算，收入增長了 15%。不包括 COVID-19 抗體收入和 2020 年第一季度 COVID 相關庫存的影響，儘管許多歐洲國家實施了封鎖，但收入增長了 5%，這主要是由 Alimta、Trulicity 和 Taltz 的銷量增長推動的。我們對我們在歐洲的業務發展勢頭感到滿意，並期待在 2021 年繼續強勁增長。

In Japan, revenue decreased 8% in constant currency, driven entirely by decreased volume for Cialis and Forteo. Net of the impact for those post-patent expiry products, Japan grew [4%] (corrected by company after the call) in constant currency, driven by Verzenio, Jardiance in collaboration with BI and Olumiant.

在日本，按固定匯率計算，收入下降了 8%，這完全是由於 Cialis 和 Forteo 的銷量下降。扣除這些專利到期後產品的影響後，在 Verzenio、Jardiance 與 BI 和 Olumiant 合作的推動下，日本按固定匯率計算增長了 [4%]（由公司在電話會議後更正）。

In China, revenue grew 26% in constant currency, driven by 32% volume growth, primarily from Tyvyt and, to a lesser extent, our diabetes portfolio. We're excited about the momentum in China as our business has accelerated significantly the past 2 quarters. Tyvyt continues its strong growth, Trulicity and Olumiant are now in the NRDL and we look forward to launch uptake for Verzenio. Revenue in the rest of the world decreased 1% in constant currency, driven primarily by continued erosion of Cialis.

在中國，收入增長 26%（按固定匯率計算），主要來自 Tyvyt 以及在較小程度上來自我們的糖尿病產品組合的 32% 的銷量增長。我們對中國的發展勢頭感到興奮，因為我們的業務在過去兩個季度顯著加速。 Tyvyt 繼續其強勁的增長，Trulicity 和 Olumiant 現在在 NRDL，我們期待推出 Verzenio 的吸收。世界其他地區的收入按固定匯率計算下降了 1%，主要是由於 Cialis 的持續侵蝕。

As shown on Slide 9, our key growth products continue to drive impressive volume growth. Despite the Q1 2020 COVID-related stocking benefit impacting year-over-year growth, these newer medicines delivered over 9 percentage point of growth this quarter with COVID antibodies also contributing roughly 14 percentage points of growth. The strong volume growth was partially offset by post-LOE products as well as insulin, whose volume growth was also meaningfully impacted by the Q1 2020 stocking benefit.

如幻燈片 9 所示，我們的主要增長產品繼續推動令人印象深刻的銷量增長。儘管 2020 年第一季度與 COVID 相關的庫存收益影響了同比增長，但這些新藥在本季度實現了超過 9 個百分點的增長，其中 COVID 抗體也貢獻了大約 14 個百分點的增長。強勁的銷量增長被 LOE 後產品和胰島素部分抵消，其銷量增長也受到 2020 年第一季度庫存收益的顯著影響。

Slide 10 highlights the contribution of our key growth products. In total, these brands generated approximately $3.1 billion in revenue this quarter and made up 52% of core business revenue. We are particularly encouraged by Trulicity's performance. 3 years ago, Trulicity was the #2 injectable GLP-1 in the U.S. market at roughly 40% share of market. Weekly scripts for the class were approximately 180,000 and a new weekly injectable entrant had just launched. Since that time, Trulicity has become the most prescribed GLP-1 in the U.S. with a 48% share of the injectable market in a class that is now twice the size at roughly 360,000 weekly scripts.

幻燈片 10 突出了我們主要增長產品的貢獻。這些品牌本季度的總收入約為 31 億美元，佔核心業務收入的 52%。我們對 Trulicity 的表現尤其感到鼓舞。 3 年前，Trulicity 是美國市場上排名第二的可注射 GLP-1，市場份額約為 40%。該課程的每週腳本大約為 180,000 份，並且剛剛推出了新的每週注射劑參賽者。從那時起，Trulicity 已成為美國處方最多的 GLP-1，在註射劑市場中佔有 48% 的份額，現在該類別的規模是每週約 360,000 個腳本的兩倍。

Trulicity continues to have the highest adherence of any diabetes medication, oral or injectable, with the additional dose of 3 and 4.5 milligram providing the potential for Trulicity to both extend the time on therapy for existing patients and compete for new patients as demonstrated by the new-to-brand share of market having increased more than 4 points since the launch of these additional doses in September 2020. As we start 2021, we are pleased with Trulicity's ability to outgrow the injectable class and establish all-time highs in new therapy starts as well as total market share.

Trulicity 繼續在任何糖尿病藥物（口服或註射劑）中具有最高的依從性，3 和 4.5 毫克的額外劑量為 Trulicity 提供了延長現有患者治療時間和競爭新患者的潛力，正如新藥所證明的那樣自 2020 年 9 月推出這些額外劑量以來，市場份額比品牌增加了 4 個百分點以上。隨著我們 2021 年開始，我們對 Trulicity 能夠超越注射類藥物並在新療法開始時創下歷史新高感到高興以及總市場份額。

We see meaningful opportunity for continued robust class growth for GLP-1s as they are still less than 1 in 10 diabetes scripts and have significant opportunity for further penetration in the first injectable space as well. With more positive readouts from the tirzepatide in type 2 diabetes this quarter, we remain focused on sustaining Trulicity's leadership position, accelerating class growth and providing continued innovation in the incretin space.

我們看到 GLP-1 類藥物持續強勁增長的有意義的機會，因為它們仍然不到十分之一的糖尿病腳本，並且在第一個可注射領域也有進一步滲透的重要機會。隨著本季度 tirzepatide 在 2 型糖尿病中的更多積極讀數，我們仍然專注於維持 Trulicity 的領導地位，加速班級增長並在腸促胰島素領域提供持續創新。

On Slide 11, we provide an update on capital allocation. In Q1, we invested nearly $3 billion to drive our future growth through a combination of business development, capital expenditure and after-tax investments in R&D. In addition, we returned nearly $800 million to shareholders via dividend. We are focused on utilizing our cash flow -- our strong cash flow to develop the next wave of new medicine through both internal and external sources, as highlighted by the recently completed in-licensing of the RIP kinase 1 inhibitor from Rigel Pharmaceuticals. We will remain active in assessing the in-licensing opportunities as well as bolt-on acquisitions, where we believe we can create shareholders' value and enhance our future growth prospects.

在幻燈片 11 中，我們提供了資本配置的最新信息。在第一季度，我們投資了近 30 億美元，通過結合業務發展、資本支出和研發的稅後投資來推動我們的未來增長。此外，我們通過股息向股東返還了近 8 億美元。我們專注於利用我們的現金流——我們強大的現金流通過內部和外部資源開發下一波新藥，正如最近完成的 Rigel Pharmaceuticals RIP 激酶1抑製劑的許可所強調的那樣。我們將繼續積極評估許可機會以及補強收購，我們相信我們可以在這些方面創造股東價值並增強我們未來的增長前景。

Turning to our 2021 financial guidance on Slide 12. We are updating our GAAP and non-GAAP guidance. We continue to support health care professionals, navigating the ongoing pandemic and driving broad vaccinations to enable return to normalcy for health care systems in the second half of the year. Despite some therapeutic class still at or below pre-COVID baselines for new therapy starts and the highlighted inventory impact on year-over-year growth, we are confident in the performance of our core business.

轉到幻燈片 12 上的 2021 年財務指導。我們正在更新我們的 GAAP 和非 GAAP 指導。我們將繼續支持醫療保健專業人員，應對持續的流行病並推動廣泛的疫苗接種，以使醫療保健系統在下半年恢復正常。儘管一些治療類別仍處於或低於新療法開始的 COVID 之前的基線，並且庫存對同比增長的影響突出，但我們對核心業務的表現充滿信心。

We are increasing our full year revenue outlook by $100 million to reflect the FX benefit realized on the top line in the first quarter. We are, however, narrowing the range for COVID-19 antibody revenue from approximately $1 billion to $2 billion to $1 billion to $1.5 billion for the year. Based on the rollout of the vaccine across major markets, current antibody utilization rate, existing U.S. government bamlanivimab supply and the transition to only supply bamlanivimab and etesevimab administered together in the U.S., we believe this update range contemplates a variety of potential scenarios. We recognize that situations across the globe can evolve quickly, and we'll plan to adapt as required moving forward. The net impact of these changes is an updated revenue range of $26.6 billion to $27.6 billion. Our outlook for gross margin percent remains unchanged with the impact of COVID-19 antibodies diluting our total gross margin percent by approximately 100 basis points.

我們將全年收入預期提高 1 億美元，以反映第一季度實現的外匯收益。然而，我們正在將今年 COVID-19 抗體收入的範圍從大約 10 億美元到 20 億美元縮小到 10 億美元到 15 億美元。基於疫苗在主要市場的推廣情況、當前的抗體利用率、美國政府現有的 bamlanivimab 供應以及在美國僅供應 bamlanivimab 和 etesevimab 的過渡，我們認為這個更新範圍考慮了各種潛在情況。我們認識到，全球形勢可能會迅速發展，我們將計劃根據需要進行調整，繼續前進。這些變化的淨影響是更新後的收入範圍為 266 億美元至 276 億美元。由於 COVID-19抗體的影響將我們的總毛利率稀釋了大約 100 個基點，我們對毛利率的前景保持不變。

For research and development, we're increasing our range from $6.5 billion to $7.7 billion to $6.9 billion to $7.1 billion. This reflects an increase of $100 million in COVID-19 antibody expense to support the advancement of a third antibody, LY-1404, as we continue to address the COVID-19 pandemic and approximately $300 million on the core business, driven by investments in donanemab for the expansion of the Phase III TRAILBLAZER-ALZ2 study and the initiation of the new Phase III study, TRAILBLAZER-ALZ3 in asymptomatic Alzheimer's patients. Our investments in donanemab is consistent with our R&D strategy to continue to bolster our pipeline to ensure long-term growth, and based on the strength of the data, invest meaningfully in innovative molecules that we believe have the potential to deliver practice changing data that could significantly improve patient outcomes in areas of high unmet need.

對於研發，我們正在將我們的範圍從 65 億美元增加到 77 億美元、69 億美元到 71 億美元。這反映了 COVID-19 抗體費用增加了 1 億美元，以支持第三抗體 LY-1404 的發展，因為我們繼續應對 COVID-19 大流行，並且在對 donanemab 的投資推動下，核心業務上約有 3 億美元用於擴展 III 期 TRAILBLAZER-ALZ2 研究和啟動新的 III 期研究 TRAILBLAZER-ALZ3在無症狀阿爾茨海默氏症患者中。我們對 donanemab 的投資符合我們的研發戰略，以繼續加強我們的管道以確保長期增長，並根據數據的優勢，對我們認為有潛力提供改變實踐的數據的創新分子進行有意義的投資，顯著改善高未滿足需求領域的患者治療效果。

We're increasing our non-GAAP range for OID to an expense of $100 million to $200 million to reflect the Alimta patent settlement in Europe I noted earlier, while our GAAP range is now income of $150 million to $250 million, which reflects the impact of equity investment gains in the first quarter. We are lowering our effective tax rate to approximately 13% to reflect higher discrete tax items in the first quarter and a lower base rate. We're lowering our non-GAAP operating margin guidance to approximately 31%. The decrease in operating margin is driven entirely by the [increased] (corrected by company after the call) investments in Alzheimer's for donanemab. Our longer-term margin expansion remains unchanged as we expect continued operating margin expansion to mid- to high 30s. Our GAAP operating margin is expected to be approximately 26%.

我們將 OID 的非 GAAP 範圍提高到 1 億至 2 億美元，以反映我之前提到的 Alimta 在歐洲的專利和解，而我們的 GAAP 範圍現在是 1.5 億至 2.5 億美元的收入，這反映了影響一季度股權投資收益。我們將有效稅率降低至約 13%，以反映第一季度較高的離散稅項和較低的基準稅率。我們將非公認會計原則的營業利潤率指引降低至約 31%。營業利潤率的下降完全是由於對阿爾茨海默氏症多納奈馬的[增加]（由公司在電話會議後更正）投資所致。我們的長期利潤率擴張保持不變，因為我們預計營業利潤率將繼續擴張至 30 多歲的中高水平。我們的 GAAP 營業利潤率預計約為 26%。

Finally, the non-GAAP range for earnings per share is now $7.80 to $8.00. The increase on the lower end of the range reflects the net benefit for the core business related to the changes to OID and tax rate as well as increased revenue, offset by increased R&D for investments in donanemab. The reduction in the upper end of the range reflects the narrow revenue range and increased R&D expense for COVID-19 therapies. Our GAAP EPS is expected to be in the range of $7.03 to $7.23, which reflects an increase to acquire the IP R&D related to completed business development transactions, other specified items related primarily to asset impairments, COVID-19 inventory charges and acquisition and integration costs as well as the benefit from net gains on investments in equity securities. We're confident in our ability to achieve our 2021 revenue goals for the core business while also delivering operating margin expansion in mid-teens EPS growth.

最後，每股收益的非公認會計原則範圍現在為 7.80 美元至 8.00 美元。範圍下限的增加反映了與 OID 和稅率變化以及收入增加相關的核心業務的淨收益，但被增加的研發投資所抵消。範圍上限的減少反映了 COVID-19 療法的收入範圍狹窄和研發費用增加。我們的公認會計原則每股收益預計在 7.03 美元至 7.23 美元之間，這反映了收購與已完成業務發展交易相關的知識產權研發、主要與資產減值、COVID-19 庫存費用以及收購和整合成本相關的其他特定項目的增加以及從股本證券投資的淨收益中獲益。我們對實現核心業務 2021 年收入目標的能力充滿信心，同時還能在十幾歲左右的每股收益增長中實現營業利潤率擴張。

As we move forward, I would encourage you to look at trends in our core business for the first half of the year, given the significant variability we saw across the period in 2020. As a reminder, revenue performance in the second quarter of 2020 was impacted by the reversal of largely all the $250 million COVID-related stocking benefit from Q1 of 2020 as well as an additional $250 million due to the significant decline in new patient prescription as health care utilization decreased and systems temporarily closed down in the face of a surging pandemic. As we look at underlying volume and share trends across our key products, we are confident in our full year outlook for the core business. And the pipeline successes in the first quarter only furthers our conviction in our mid-term and long-term outlook for continued revenue growth and operating margin expansion.

隨著我們向前邁進，鑑於我們在 2020 年期間看到的顯著變化，我鼓勵您查看我們上半年核心業務的趨勢。提醒一下，2020 年第二季度的收入表現是受到 2020 年第一季度與 COVID 相關的 2.5 億美元庫存福利的大部分逆轉以及由於醫療保健利用率下降和系統因面臨新冠肺炎疫情而暫時關閉而導致新患者處方大幅下降而額外增加的 2.5 億美元的影響流行病蔓延。當我們審視主要產品的潛在銷量和分享趨勢時，我們對核心業務的全年前景充滿信心。第一季度管道的成功只會進一步增強我們對持續收入增長和營業利潤率擴大的中長期前景的信念。

Now I will turn the call over to Dan to highlight our progress in R&D.

現在我將把電話轉給 Dan 來強調我們在研發方面的進展。

Thanks, Anat. 2021 is clearly off to a very positive start for R&D at Lilly with strong pipeline progress already and more potential catalysts on the way. Before I get into the broader portfolio update, I'll spend a few minutes highlighting results from tirzepatide's first 4 top line readouts from the Phase III SURPASS program, including the strong results from SURPASS-2, the head-to-head trial with semaglutide 1 milligram. This program is aptly named as we've seen tirzepatide surpass our expectations through these initial readouts, displaying significantly greater hemoglobin A1C reduction, weight loss and percent of patients reaching normal glucose levels than any GLP-1 on the market.

謝謝，阿納特。 2021 年禮來公司的研發工作顯然有了一個非常積極的開端，管道進展強勁，更多潛在的催化劑也在路上。在我進入更廣泛的產品組合更新之前，我將花幾分鐘重點介紹 tirzepatide 在 III 期 SURPASS 計劃中的前 4 個頂級讀數的結果，包括 SURPASS-2（與 semaglutide 的頭對頭試驗）的強勁結果1毫克。該計劃的名稱恰如其分，因為我們通過這些初步讀數看到 tirzepatide 超出了我們的預期，與市場上的任何 GLP-1 相比，顯示的血紅蛋白 A1C 減少、體重減輕和達到正常葡萄糖水平的患者百分比顯著更高。

On Slide 13, you can see impressive performance in the efficacy estimate analysis in glycemic control for tirzepatide with each dose demonstrating superiority in each trial across a range of patient populations, comparators and background medications. The clear highlight is the impressive A1C reduction of the 5-milligram dose across each of these 3 -- each of these different patient populations while the higher doses provide additional glucose control up to and surpassing 2.5% A1C reductions.

在幻燈片 13 上，您可以看到 tirzepatide 在血糖控制中的療效評估分析中的出色表現，每個劑量在每個試驗中都證明了在一系列患者人群、比較藥物和背景藥物中的優勢。明顯的亮點是這 3 種患者中每一種的 5 毫克劑量的 A1C 令人印象深刻地減少了 - 這些不同的患者群體中的每一種，而更高的劑量提供了額外的葡萄糖控制，高達並超過 2.5% 的 A1C 減少。

Moving to Slide 14. You can see how tirzepatide performed across all 3 doses in terms of patients achieving HbA1c below 5.7%, the normal glycemic level seen in people without type 2 diabetes. We believe this is an exciting finding that may reset expectations for the impact diabetes medications could have for patients. Using the efficacy estimate analysis across SURPASS-1, 2 and 3, we see about half of the patients on the 15-milligram dose of tirzepatide achieve this remarkable level of HbA1c control.

轉到幻燈片 14。您可以看到 tirzepatide 在所有 3 種劑量中的表現如何使 HbA1c 低於 5.7%（在沒有 2 型糖尿病的人中看到的正常血糖水平）的患者。我們相信這是一個令人興奮的發現，它可能會重新設定人們對糖尿病藥物可能對患者產生影響的預期。使用 SURPASS-1、2 和 3 的療效估計分析，我們看到大約一半的 15 毫克劑量 tirzepatide 的患者達到了這一顯著的 HbA1c 控制水平。

In SURPASS-5, which focused on patients on background insulin glargine, 62% of patients on 15-milligram tirzepatide achieved this level of A1C compared to only 3% of patients in the placebo group. Remember, this is a patient population on background basal insulin with an average duration of diabetes of over 13 years. Achieving this level of glucose control in such a population is something that prior to GIP/GLP-1 agonists like tirzepatide, we did not even contemplate as possible.

在專注於背景甘精胰島素患者的 SURPASS-5 中，使用 15 毫克 tirzepatide 的患者中有 62% 的患者達到了這一 A1C 水平，而安慰劑組中只有 3% 的患者。請記住，這是一個使用基礎胰島素的患者群體，其糖尿病平均病程超過 13 年。在這樣的人群中實現這種水平的葡萄糖控制是在像 tirzepatide 這樣的 GIP/GLP-1 激動劑之前，我們甚至沒有考慮過。

On Slide 15, we show the efficacy estimate analysis for weight reduction across the 4 studies. Here again, we see levels of efficacy that previously were thought unobtainable with incretin therapy in type 2 diabetes patients. As we and others have discussed, studies like AWARD-11 and SUSTAIN-FORTE have begun to show the limit of what fully hitting the GLP-1 mechanism can accomplish for weight loss and A1C. There appear to be diminishing returns as doses of GLP-1 alone fully saturate the GLP-1 receptor-mediated mechanism and a flattening of the dose response curve occurs.

在幻燈片 15 上，我們展示了 4 項研究中減輕體重的療效估計分析。在這裡，我們再次看到了以前認為在 2 型糖尿病患者中使用腸促胰島素治療無法獲得的療效水平。正如我們和其他人所討論的那樣，像 AWARD-11 和 SUSTAIN-FORTE 這樣的研究已經開始表明，完全達到 GLP-1 機制對於減肥和 A1C 的作用是有限的。由於單獨的 GLP-1 劑量使 GLP-1 受體介導的機製完全飽和，並且劑量反應曲線變平，因此似乎收益遞減。

And then you look at this slide, including importantly, SURPASS-2. And you can see quite clearly that there's something different going on here as the dual GIP/GLP-1 receptor agonist is beyond the flattening of the dose response curve of GLP-1 performance, which we believe evidences the power of adding in the GIP mechanisms. Highlights from these studies include the 15-milligram dose delivering 14% weight reduction in SURPASS-3, noting here weight gain of 3% on insulin degludec comparator, the 15-milligram dose nearly doubling the weight reduction of semaglutide 1-milligram in SURPASS-2 and strong performance from the 5 and 10-milligram doses with statistically superior weight loss, even as high as 11% on the 10-milligram dose versus placebo or active comparators.

然後你看看這張幻燈片，包括重要的 SURPASS-2。你可以很清楚地看到這裡發生了一些不同的事情，因為雙重 GIP/GLP-1 受體激動劑超出了 GLP-1 性能的劑量反應曲線的平坦化，我們認為這證明了添加 GIP 機制的力量.這些研究的亮點包括 15 毫克劑量可使 SURPASS-3 中的體重減輕 14%，在此註意到德谷胰島素比較器的體重增加 3%，15 毫克劑量幾乎使 SURPASS-中 1 毫克索馬魯肽的體重減輕增加了一倍。 2 和 5 和 10 毫克劑量的強勁表現，具有統計學上優越的減肥效果，與安慰劑或活性比較劑相比，10 毫克劑量甚至高達 11%。

We're encouraged that in these 40 and 52-week studies, we haven't yet seen the weight loss curves plateau on the higher doses. It's really exciting to think about how tirzepatide could potentially perform with the longer duration of treatment that we'll see in future studies. We had a lot of confidence in the efficacy data coming out of Phase II. But there was a lot we didn't yet know about safety and tolerability. Recall, for example, that the primary Phase II trial had only about 200 patients on therapy and patients were only on therapy for 26 weeks.

我們感到鼓舞的是，在這些 40 周和 52 週的研究中，我們還沒有看到高劑量下的體重減輕曲線趨於平穩。想想 tirzepatide 如何在未來的研究中看到更長的治療持續時間，這真的很令人興奮。我們對第二階段的療效數據充滿信心。但是關於安全性和耐受性，我們還有很多不知道的地方。回想一下，例如，最初的 II 期試驗只有大約 200 名患者接受治療，而患者僅接受了 26 週的治療。

As we look at Slide 16, we've been pleased to see through these 4 SURPASS readouts that the overall safety profile was similar to the well-established GLP-1 receptor agonist class and the most commonly reported adverse events were GI-related and mild to moderate in severity. We're particularly encouraged by the potential impact of the optimized dose escalation scheme, and accordingly, by the tolerability profile observed in the Phase III program, which improved greatly in comparison to Phase II, including the lower rates of nausea, diarrhea and vomiting that we've seen, consistent with what we saw in Phase III studies for other well-tolerated and highly used incretin therapies, including our own Trulicity. In addition, we're pleased with the discontinuation rates due to adverse events, which have ranged from 3% to 11% across doses in these studies.

當我們查看幻燈片 16 時，我們很高興通過這 4 個 SURPASS 讀數看到整體安全性概況與成熟的 GLP-1 受體激動劑類別相似，並且最常報告的不良事件是與胃腸道相關的輕微不良事件嚴重程度適中。我們對優化劑量遞增方案的潛在影響感到特別鼓舞，因此，在第三階段計劃中觀察到的耐受性特徵與第二階段相比有了很大改善，包括噁心、腹瀉和嘔吐的發生率降低我們已經看到，與我們在 III 期研究中看到的其他耐受性良好和高度使用的腸促胰島素療法的結果一致，包括我們自己的 Trulicity。此外，我們對因不良事件導致的停藥率感到滿意，在這些研究中，不同劑量的停藥率在 3% 至 11% 之間。

Stepping back from the data a bit, we're excited about the safety and efficacy results across all doses, but perhaps especially so for the efficacy of the 5-milligram dose, which has performed well in each study, including showing superiority to semaglutide 1 milligram in SURPASS-2 on both A1C reduction and weight loss. I think these data show that the 5-milligram dose could be a great first incretin that can potentially deliver best-in-class efficacy with tolerability that is as good or better than other leading incretins. So we have the low maintenance dose of 5 milligrams that, if approved, could potentially be appropriate for many patients with physicians knowing they could have higher doses available as they continue management of disease.

稍微退後一步，我們對所有劑量的安全性和有效性結果感到興奮，但也許對 5 毫克劑量的療效尤其如此，該劑量在每項研究中都表現良好，包括顯示優於 semaglutide 1 SURPASS-2 中的毫克對 A1C 減少和體重減輕。我認為這些數據表明，5 毫克劑量可能是一個很好的第一個腸促胰島素，它可能提供一流的療效，其耐受性與其他領先的腸促胰島素一樣好或更好。因此，我們有 5 毫克的低維持劑量，如果獲得批准，可能適用於許多患者，因為醫生知道他們可以在繼續管理疾病時獲得更高的劑量。

Tirzepatide could provide patients with the opportunity to set treatment goals that might surpass what was previously thought possible in type 2 diabetes, both in terms of getting patients to normal glucose control, which has never been contemplated as a potential treatment goal, as well as for impressive weight loss with the highest dose of tirzepatide having roughly double the weight loss of semaglutide 1 milligram in SURPASS-2. Today, type 2 diabetes is largely a treat-to-fail disease.

Tirzepatide 可以讓患者有機會設定可能超過以前認為的 2 型糖尿病的治療目標，無論是在讓患者達到正常血糖控制（這從未被認為是潛在的治療目標）方面，還是為在 SURPASS-2 中，最高劑量的 tirzepatide 的體重減輕大約是 semaglutide 1 毫克的兩倍。今天，2 型糖尿病在很大程度上是一種治療失敗的疾病。

With these results, tirzepatide, if approved, could potentially provide doctors options to enable early control of glucose and weight. This has the potential to translate to improved levels of end organ protection and a more meaningful reduction in disease complications than has yet been seen. We'll be testing this potential for tirzepatide in ongoing and planned studies in diabetes, obesity, heart failure and NASH. Accordingly, we've now initiated SURMOUNT-2, 3 and 4 for tirzepatide in obesity and top line results from SURMOUNT-1 are expected next year.

有了這些結果，如果獲得批准，tirzepatide 可能會為醫生提供早期控制血糖和體重的選擇。這有可能轉化為提高終末器官保護水平，並比以往更有意義地減少疾病並發症。我們將在正在進行和計劃進行的糖尿病、肥胖症、心力衰竭和 NASH 研究中測試 tirzepatide 的這種潛力。因此，我們現在已經啟動了 SURMOUNT-2、3 和 4 治療肥胖症的替西帕肽，預計明年 SURMOUNT-1 的一線結果。

Moving back to diabetes. The top line readout for SURPASS-4, which is in a high cardiovascular risk population and we believe will provide an important contribution to our CV safety assessment, is the gating trial for global submissions in type 2 diabetes. Completion of this trial has always been contingent on accruing a prespecified number of CV events. We've achieved the necessary events, which triggers bringing patients in for final treatment and safety visits before moving the trial to completion. Based on this update, we anticipate a top line readout by the middle of this year. We look forward to disclosing the results of SURPASS-1, 2, 3 and 5 at the ADA 2021 Virtual Meeting, which will include a 90-minute ADA symposium featuring these results the morning of June 29.

回到糖尿病。 SURPASS-4 的頂線讀數是心血管風險高的人群，我們相信這將為我們的 CV 安全性評估做出重要貢獻，它是全球 2 型糖尿病提交的門控試驗。該試驗的完成始終取決於累積預定數量的 CV 事件。我們已經完成了必要的事件，這些事件促使患者在完成試驗之前進行最終治療和安全訪問。基於此更新，我們預計到今年年中將發布頂線讀數。我們期待在 ADA 2021 虛擬會議上披露 SURPASS-1、2、3 和 5 的結果，其中將包括 6 月 29 日上午舉行的 90 分鐘 ADA 專題討論會。

While we're excited with the progress of tirzepatide, we think innovation in the incretin space is not over. At ADA, we'll also be discussing preclinical and Phase I data for our glucagon/GLP/GIP triagonist, also known as GGG, which we're pleased to announce we'll be moving into Phase II later this quarter. We've previously commented that in this space, we have a high bar for progressing molecules in development, one that has been raised recently by tirzepatide. While it's still early, we're advancing GGG to Phase II based on our belief that it could exceed the benefits seen with tirzepatide. With our GGG molecule, we expect to see even more weight loss than what can be achieved with tirzepatide while preserving glucose-lowering efficacy. In addition, due to glucagon's direct action on the liver, we'd also hope to see benefits in NASH. Consequently, our ambitious Phase II program is designed to evaluate GGG for obesity, type 2 diabetes and NASH.

雖然我們對 tirzepatide 的進展感到興奮，但我們認為腸促胰島素領域的創新還沒有結束。在 ADA，我們還將討論我們的胰高血糖素/GLP/GIP 三方劑（也稱為 GGG）的臨床前和 I 期數據，我們很高興地宣布我們將在本季度晚些時候進入 II 期。我們之前曾評論說，在這個領域，我們對分子的發展有很高的標準，最近由 tirzepatide 提出了這一標準。雖然現在還為時過早，但我們正在將 GGG 推進到第二階段，因為我們相信它可能會超過 tirzepatide 所帶來的益處。使用我們的 GGG 分子，我們希望看到比使用 tirzepatide 在保持降糖功效的同時可以實現更多的體重減輕。此外，由於胰高血糖素對肝臟的直接作用，我們也希望看到 NASH 的益處。因此，我們雄心勃勃的 II 期計劃旨在評估 GGG 對肥胖、2 型糖尿病和 NASH 的影響。

In addition to our next-generation incretins, we're also very excited by our novel weekly insulin, basal insulin-Fc. Thanks to Lilly's work on Trulicity, weekly incretin therapy is now the standard of care in the GLP-1 space. And together with tirzepatide, we hope incretin-based therapies will become the standard of care in the first injectable space for people with type 2 diabetes. For those people who need basal insulin therapy in addition to their incretin therapy, we'd like to make weekly insulin therapy possible, ultimately avoiding daily injections completely. We'll give an update at ADA on our novel weekly basal insulin. We plan to have an investor call in the morning of July 1 to discuss the data releases at ADA for tirzepatide, GGG and weekly basal insulin.

除了我們的下一代腸促胰島素，我們還對我們的新型每週胰島素基礎胰島素-Fc 感到非常興奮。由於 Lilly 在 Trulicity 方面的工作，每週腸促胰島素治療現在已成為 GLP-1 領域的護理標準。與 tirzepatide 一起，我們希望基於腸促胰島素的療法將成為 2 型糖尿病患者第一個注射空間的護理標準。對於那些除了腸促胰島素治療外還需要基礎胰島素治療的人，我們希望每週一次的胰島素治療成為可能，最終完全避免每天注射。我們將在 ADA 上更新我們新穎的每週基礎胰島素。我們計劃在 7 月 1 日上午召開投資者電話會議，討論 ADA 發布的替西帕肽、GGG 和每週基礎胰島素的數據。

While the progress in our diabetes portfolio is compelling, Lilly has continued to advance the rest of our pipeline this quarter. Slide 17 shows select pipeline opportunities as of April 23 and Slide 18 shows potential key events for the year. In addition to the progress on tirzepatide I just discussed, major developments since our last earnings call include progress with donanemab on multiple fronts. In terms of data, we presented detailed results at AD/PD showing donanemab met its primary endpoint, significantly slowing cognitive decline compared to placebo on the integrated Alzheimer's disease rating scale, a composite measure of cognition and daily function in patients with early symptomatic Alzheimer's disease. And data from secondary analyses showed donanemab consistently slowed cognitive and functional decline with ranges between 20% and 40% in all secondary endpoints with nominal statistical significance at multiple time points compared to placebo.

雖然我們的糖尿病產品組合取得了令人矚目的進展，但禮來公司在本季度繼續推進我們的其餘產品線。幻燈片 17 顯示了截至 4 月 23 日的選定管道機會，幻燈片 18 顯示了今年潛在的關鍵事件。除了我剛剛討論的 tirzepatide 的進展之外，自我們上次財報電話會議以來的主要進展包括多納奈馬在多個方面的進展。在數據方面，我們在 AD/PD 上展示了詳細的結果，顯示多那奈馬達到其主要終點，與安慰劑相比，在綜合阿爾茨海默病評定量表上顯著減緩認知下降，這是對早期症狀性阿爾茨海默病患者認知和日常功能的綜合測量.來自二次分析的數據顯示，與安慰劑相比，在所有次要終點中，多納奈單抗始終減緩認知和功能下降，範圍在 20% 至 40% 之間，在多個時間點具有標稱統計學意義。

On the clinical front, as we discussed in detail on our call last month, we expanded TRAILBLAZER-ALZ 2 to be a Phase III study, and it's now enrolling quickly. And today, we're announcing that we will start a new Phase III study, TRAILBLAZER-ALZ 3, in asymptomatic Alzheimer's disease. This trial is anticipated to begin enrollment later this year. Our goal here is to enroll patients who already have Alzheimer's brain pathology but don't yet have any clinical symptoms. The study will have development and progression of Alzheimer's disease symptoms as the primary endpoint. And we anticipate it will take approximately 3 years from completion of enrollment to reach a sufficient number of events. We'll be testing if a short course of donanemab treatment at the start of the trial can prevent progression in a substantial fraction of patients over the subsequent several years. These types of trials are extremely challenging to enroll and conduct. But here, we're buoyed by our expertise in biomarkers, including both PET scans and importantly, our plasma PTau217 assay.

在臨床方面，正如我們在上個月的電話會議中詳細討論的那樣，我們將 TRAILBLAZER-ALZ 2 擴展為 III 期研究，現在正在迅速註冊。今天，我們宣布我們將開始一項針對無症狀阿爾茨海默病的新 III 期研究 TRAILBLAZER-ALZ 3。該試驗預計將於今年晚些時候開始招生。我們的目標是招募已經患有阿爾茨海默氏症但尚未出現任何臨床症狀的患者。該研究將阿爾茨海默病症狀的發展和進展作為主要終點。我們預計從完成註冊到達到足夠數量的活動大約需要 3 年時間。我們將測試在試驗開始時的短期多納奈單抗治療是否可以在隨後的幾年中阻止大部分患者的進展。這些類型的試驗在招募和實施方面極具挑戰性。但在這裡，我們在生物標誌物方面的專業知識鼓舞了我們，包括 PET 掃描，重要的是，我們的血漿 PTau217 檢測。

On the regulatory front, based on feedback from the FDA, we currently do not see a path forward for near-term submission and approval based on the first TRAILBLAZER-ALZ study alone. As you know, the unmet need in Alzheimer's disease is significant. So while we remain focused on speeding up enrollment and completion of our second pivotal study, TRAILBLAZER-ALZ 2, we are continuing to actively engage with the FDA and are fully exploring any opportunities for early submission.

在監管方面，根據 FDA 的反饋，我們目前看不到僅基於第一個 TRAILBLAZER-ALZ 研究的近期提交和批准的前進道路。如您所知，阿爾茨海默病的未滿足需求意義重大。因此，儘管我們仍然專注於加快註冊和完成我們的第二個關鍵研究 TRAILBLAZER-ALZ 2，但我們將繼續積極與 FDA 合作，並充分探索任何提前提交的機會。

Another highlight this quarter was the initiation of pirtobrutinib's Phase III program with study start in chronic lymphocytic leukemia as monotherapy. We're also proud of the continuation of our work against COVID-19, including a planned transition from bamlanivimab alone to the administration of bamlanivimab and etesevimab together for the treatment of COVID-19 in the U.S., accomplished by first gaining Emergency Use Authorization for bamlanivimab and etesevimab administered together in February and then our request for revocation of the EUA for bamlanivimab alone, which FDA subsequently granted.

本季度的另一個亮點是 pirtobrutinib 的 III 期項目的啟動，該項目以慢性淋巴細胞白血病作為單一療法的研究開始。我們也為我們繼續針對 COVID-19 開展的工作感到自豪，包括計劃在美國從單獨使用 bamlanivimab 過渡到同時使用 bamlanivimab 和 etesevimab 治療 COVID-19，這是通過首先獲得緊急使用授權來完成的bamlanivimab 和 etesevimab 於 2 月一起給藥，然後我們要求撤銷單獨 bamlanivimab 的 EUA，FDA 隨後批准了這一請求。

We also submitted bamlanivimab and etesevimab administered together for regulatory review in Europe. And we initiated the evaluation of bamlanivimab with VIR-7831 in collaboration with Vir and GSK as well as started trials with a new, potentially broadly neutralizing antibody, LY-1404, in collaboration with AbCellera in case new combinations are needed to fight variants. We announced top line Phase III results evaluating baricitinib on top of standard of care, which did not meet statistical significance on the primary endpoint for treatment of COVID-19 but did result in a significant reduction of death from any cause by 38% by day 28. And baricitinib received regulatory approval in conjunction with remdesivir as a treatment for COVID-19 in Japan.

我們還提交了 bamlanivimab 和 etesevimab 一起在歐洲進行監管審查。我們與 Vir 和 GSK 合作啟動了使用 VIR-7831 對 bamlanimab 的評估，並與 AbCelera 合作開始使用一種新的、可能廣泛中和的抗體 LY-1404 進行試驗，以防需要新的組合來對抗變異。我們公佈了在護理標準之上評估巴瑞替尼的頂級 III 期結果，該結果在 COVID-19 治療的主要終點上沒有達到統計學意義，但在第 28 天確實使全因死亡顯著減少了 38% . 巴瑞替尼與瑞德西韋一起在日本獲得了監管部門的批准，用於治療 COVID-19。

Our work on tirzepatide, donanemab and pirtobrutinib brings great potential for patients in the long term and is highly prioritized at Lilly. Our work on COVID-19 is another clear highlight, where we moved quickly to help address an unmet medical need in the midst of a pandemic. We're optimistic though that this need will wane in the coming years. Beyond these significant efforts, there's been progress across many other commercial stage and clinical stage assets.

從長遠來看，我們在 tirzepatide、donanemab 和 pirtobrutinib 方面的工作為患者帶來了巨大的潛力，並在禮來公司高度優先考慮。我們在 COVID-19 方面的工作是另一個明顯的亮點，我們迅速採取行動幫助解決大流行期間未滿足的醫療需求。我們樂觀地認為，這種需求將在未來幾年內減弱。除了這些重大努力之外，許多其他商業階段和臨床階段資產也取得了進展。

Starting in oncology, we're pleased with the approval of selpercatinib for non-small cell lung cancer and thyroid cancer in Europe. We're also pleased that the results of monarchE, our adjuvant breast cancer study, are now submitted in Japan, along with Europe, China and the U.S. As you know, the primary endpoint for the study was invasive disease-free survival, which we hit at the interim analysis. As anticipated, this hazard ratio continues to strengthen over time as more events have accrued. Important secondary endpoints for the study include distant relapse-free survival and overall survival.

從腫瘤學開始，我們很高興 selpercatinib 在歐洲獲批用於治療非小細胞肺癌和甲狀腺癌。我們也很高興我們的輔助乳腺癌研究 monarchE 的結果現在與歐洲、中國和美國一起提交給日本。如您所知，該研究的主要終點是無侵襲性無病生存，我們命中中期分析。正如預期的那樣，隨著更多事件的發生，這種風險比會隨著時間的推移而繼續增強。該研究的重要次要終點包括無遠處復發生存期和總生存期。

For the U.S. submission, the FDA has noted, and we agree, that the OS data are immature and thus unreliable as we shared in the JCO publication last year. FDA has, therefore, asked us to see an updated OS analysis during the review cycle to determine that OS is trending in favor of Verzenio. Given the robust distant relapse-free survival data, we're highly confident that the overall survival data will eventually reflect and reinforce the survival benefit. But it takes time for these events to accrue, especially in the adjuvant setting.

對於美國提交的文件，FDA 已經註意到，我們同意，操作系統數據不成熟，因此不可靠，正如我們去年在 JCO 出版物中分享的那樣。因此，FDA 要求我們在審查週期中查看更新的 OS 分析，以確定 OS 趨勢有利於 Verzenio。鑑於可靠的遠期無復發生存數據，我們非常有信心總體生存數據最終將反映和加強生存益處。但這些事件的累積需要時間，尤其是在輔助環境中。

In immunology, we have positive Phase III readouts for baricitinib in alopecia areata, a disease with significant unmet medical need, and we look forward to regulatory submissions starting in the second half of this year. We also announced that the FDA extended the review period for baricitinib for atopic dermatitis by 3 months, another disease where we think JAK inhibition could potentially alleviate important unmet medical needs.

在免疫學方面，我們在斑禿中獲得了巴瑞替尼的 III 期陽性讀數，這是一種嚴重未滿足醫療需求的疾病，我們期待從今年下半年開始提交監管文件。我們還宣布，FDA 將巴瑞替尼治療特應性皮炎的審查期延長了 3 個月，這是我們認為 JAK 抑制可能緩解重要未滿足醫療需求的另一種疾病。

With mirikizumab, we reported positive Phase III results in ulcerative colitis in the 12-week induction study, hitting the primary endpoint and all key secondary endpoints, and we look forward to seeing the maintenance data early next year. We also have updates to mirikizumab psoriasis program. While the OASIS program generated positive results with safety and efficacy similar to other IL-23p19s, we believe the psoriasis market is well served with highly effective treatment options, including Taltz.

使用 mirikizumab，我們在為期 12 週的誘導研究中報告了潰瘍性結腸炎的 III 期陽性結果，達到了主要終點和所有關鍵的次要終點，我們期待在明年初看到維持數據。我們還更新了 mirikizumab 銀屑病計劃。雖然 OASIS 計劃產生了與其他 IL-23p19 相似的安全性和有效性的積極結果，但我們相信銀屑病市場有很好的高效治療選擇，包括 Taltz。

Lilly's immunology strategy is to focus our new molecules and indications on areas where patients have significant unmet needs, not merely adding new options or leveraging commercial presence to create a space, where effective solutions like Taltz already exist for patients. Therefore, we will not pursue submission of mirikizumab in psoriasis, but instead, we'll focus our efforts on the ulcerative colitis and Crohn's disease indications, where unmet medical need is higher and where we believe the potential of the IL-23p19 mechanism to create a new standard of care is greater.

禮來（Lilly）的免疫學戰略是將我們的新分子和適應症集中在患者有重大未滿足需求的領域，而不僅僅是增加新的選擇或利用商業存在來創造一個空間，其中 Taltz 等有效的解決方案已經為患者提供。因此，我們不會尋求提交 mirikizumab 治療銀屑病，相反，我們將把精力集中在潰瘍性結腸炎和克羅恩病適應症上，在這些適應症中，未滿足的醫療需求更高，並且我們相信 IL-23p19 機制創造的潛力新的護理標準更高。

In addition to late-stage progress, our early-stage portfolio continues to advance with the introduction of 5 new Phase I assets and the attrition of 2. In addition to the progress we've made in just the first few months of the year, we anticipate important developments for the remainder of 2021, including the final readout for tirzepatide's Phase III type 2 diabetes program, SURPASS-4, noted earlier; Phase III results for Jardiance in HFpEF and for lebrikizumab in atopic dermatitis; regulatory actions for Jardiance for HFrEF, Verzenio in the adjuvant setting for ER-positive breast cancer, baricitinib for atopic dermatitis and tanezumab for osteoarthritis pain, where we previously noted our disappointment in the outcome of the Tanezumab Advisory Committee; the presentation of Phase I data for our oral SERD; the initiation of Phase I for a BCL2 inhibitor and for KRAS-G12C inhibitor; along with the filing of an IND for our next-generation RET inhibitor later this year as we announced at AACR; and the Phase II readout for zagotenemab, our anti-tau antibody for early Alzheimer's disease.

除了後期進展，我們的早期投資組合繼續推進，引入了 5 項新的第一階段資產和 2 項資產的減員。除了我們在今年前幾個月取得的進展外，我們預計 2021 年剩餘時間的重要進展，包括前面提到的 tirzepatide 的 III 期 2 型糖尿病項目 SURPASS-4 的最終讀數； Jardiance 治療 HFpEF 和 lebrikizumab 治療特應性皮炎的 III 期結果；對 HFrEF 的 Jardiance、ER 陽性乳腺癌輔助環境中的 Verzenio、特應性皮炎的巴瑞替尼和骨關節炎疼痛的 tanezumab 的監管行動，我們之前註意到我們對 Tanezumab 諮詢委員會的結果感到失望；為我們的口頭 SERD 提供第一階段數據； BCL2抑製劑和KRAS-G12C抑製劑的I期啟動；正如我們在 AACR 上宣布的那樣，我們在今年晚些時候為我們的下一代 RET 抑製劑提交了 IND 申請；以及我們針對早期阿爾茨海默病的抗 tau 抗體 zagotenemab 的 II 期讀數。

We believe our continued pipeline success drives increasing visibility to meaningful long-term growth, and we look forward to continued progress across our portfolio in the coming quarters.

我們相信我們持續的管道成功推動了有意義的長期增長的可見性提高，我們期待在未來幾個季度我們的投資組合繼續取得進展。

Now I turn the call back over to Dave for some closing remarks.

現在我把電話轉回給戴夫做一些結束語。

Thanks, Dan. Before we go to Q&A, let me briefly sum up the progress we've made to start the year. Amid several moving pieces in a challenging health care environment, we are excited by the momentum we are seeing. Our business grew 16% in the first quarter with the core business growing 7%, adjusted for COVID-19 antibody revenue and last year's COVID-19-related inventory stocking benefit. Our top line growth continues to be strong, driven strongly by volume across our key growth products, which account for more than half of our core business.

謝謝，丹。在進行問答之前，讓我簡要總結一下我們在年初取得的進展。在充滿挑戰的醫療保健環境中，有幾個動人的部分，我們對所看到的勢頭感到興奮。我們的業務在第一季度增長了 16%，核心業務增長了 7%，根據 COVID-19 抗體收入和去年與 COVID-19 相關的庫存收益進行了調整。我們的收入增長繼續強勁，這主要得益於我們主要增長產品的銷量，這些產品占我們核心業務的一半以上。

Net of the significant impact from foreign exchange on international inventories sold, our operating margin was in line with our expectations as we continue to expect operating margin expansion throughout the year and further expansion in years to come. We made significant progress developing new medicines with many more data readouts expected this year. Advances for tirzepatide, donanemab, pirtobrutinib, Verzenio, mirikizumab, Retevmo and Olumiant, serve as a reminder of the breadth and depth of opportunities we have to sustain robust long-term growth. We returned nearly $800 million to shareholders, being increased dividend, reflecting confidence in the ongoing strength of our business.

扣除外匯對已售國際庫存的重大影響後，我們的營業利潤率符合我們的預期，因為我們繼續預計全年營業利潤率將擴大，並在未來幾年進一步擴大。我們在開發新藥方面取得了重大進展，預計今年將獲得更多數據。 tirzepatide、donanemab、pirtobrutinib、Verzenio、mirikizumab、Retevmo 和 Olumiant 的進展提醒我們要維持強勁的長期增長所需要的機會的廣度和深度。我們向股東返還了近 8 億美元，增加了股息，反映了對我們業務持續實力的信心。

I want to say thank you to my Lilly teammates, whose commitment to excellence and dedication to our purpose of bringing innovative new medicines to patients is inspiring and drove these accomplishments amidst ongoing pandemic headwinds. While our people, health care providers and patients continue to face near-term challenges associated with COVID-19, our long-term outlook is as bright as ever.

我要感謝我的禮來 (Lilly) 隊友，他們對卓越的承諾和對我們為患者帶來創新新藥的目標的奉獻精神鼓舞人心，並在持續的大流行逆風中推動了這些成就。雖然我們的員工、醫療保健提供者和患者繼續面臨與 COVID-19 相關的近期挑戰，但我們的長期前景與以往一樣光明。

This concludes our prepared remarks. And now I'll turn the call over to Kevin to moderate the Q&A session.

我們準備好的評論到此結束。現在我將把電話轉給 Kevin 來主持問答環節。

Thanks, Dave. (Operator Instructions) Toni, can you please provide the instructions for the Q&A session? And then we're ready for the first caller.

謝謝，戴夫。 （操作員說明）Toni，您能提供問答環節的說明嗎？然後我們準備好迎接第一個來電者。

(Operator Instructions) Our first question comes from the line of Chris Schott with JPMorgan.

（操作員說明）我們的第一個問題來自摩根大通的 Chris Schott。

I've just got 2 on the pipeline. I guess, first, on Verzenio, did I hear that you mentioned FDA is looking for updated OS data as part of the review? So I was just wondering when you'll have that data. And does that push out approval timelines in any meaningful way that we need to think about?

我剛有2個在管道上。我想，首先，在 Verzenio 上，我是否聽說您提到 FDA 正在尋找更新的操作系統數據作為審查的一部分？所以我只是想知道你什麼時候會有這些數據。這是否會以我們需要考慮的任何有意義的方式推遲批准時間表？

And then the second one I had was on tirzepatide. I guess, in light of the data you've seen from the SURPASS studies, does that -- has that changed how you think about what patient populations you'll focus on from a commercial standpoint or your go-to-market strategy? And I guess, as part of that, as we think about tirzepatide coming to market, do you expect substantial switches from Trulicity? Or is tirzepatide growth more about new patient starts and kind of expanding the market?

然後我吃的第二個是替西帕肽。我想，根據您從 SURPASS 研究中看到的數據，這是否改變了您對從商業角度或進入市場策略的角度關注哪些患者群體的看法？我想，作為其中的一部分，當我們考慮 tirzepatide 進入市場時，您是否期望 Trulicity 發生重大轉變？或者 tirzepatide 的增長更多地是關於新患者的開始和擴大市場？

Thanks, Chris. We'll go to Anne for the Verzenio question and then Mike on tirzepatide.

謝謝，克里斯。我們將向 Anne 詢問 Verzenio 問題，然後向 Mike 詢問 tirzepatide。

Well, thanks, Chris, for the question on Verzenio. And so we will be delivering this data set to the FDA without delaying our standard review timing. We can't really comment on what the FDA will do with the data or the application, but these discussions are progressing as planned. Important to note, as the data matures, I think, as Dan said, given the strength of the DRFS hazard ratio, remember, it was a 0.687 hazard ratio with a very strong p-value, we are highly confident that the OS will trend in favor of Verzenio. So really, what we believe we're discussing is when that will occur.

好吧，謝謝克里斯，關於 Verzenio 的問題。因此，我們將向 FDA 提供這些數據集，而不會延遲我們的標準審查時間。我們無法真正評論 FDA 將如何處理數據或申請，但這些討論正在按計劃進行。需要注意的重要一點是，隨著數據的成熟，我認為，正如 Dan 所說，鑑於 DRFS 風險比的強度，請記住，這是一個 0.687 的風險比，具有非常強的 p 值，我們非常有信心操作系統將趨勢支持韋爾澤尼奧。所以真的，我們相信我們正在討論的是什麼時候會發生。

So obviously, as I said, we can't comment on the discussion with FDA, but we do look forward to working with them on bringing this medicine to patients. And maybe just a comment to reference how immature this data is. At the time of the interim analysis that we published in JCO late last year, there were 39 deaths in the abema arm and 37 in the control arm. So that makes it really challenging to interpret this data when there's over 5,000 patients in the study. Thanks for the question.

所以很明顯，正如我所說，我們不能對與 FDA 的討論發表評論，但我們確實期待與他們合作，將這種藥物帶給患者。也許只是一個評論來參考這些數據是多麼不成熟。在我們去年年底在 JCO 上發表的中期分析時，abema 組有 39 人死亡，對照組有 37 人死亡。因此，當研究中有超過 5,000 名患者時，解釋這些數據變得非常具有挑戰性。謝謝你的問題。

Thanks, Anne. Mike?

謝謝，安妮。麥克風？

Chris, thanks for your question. No, the tirzepatide results have not changed the way we want to position tirzepatide in the marketplace. Obviously very pleased with those results. We're also just really blessed to have both Trulicity and tirzepatide. Our goal will be to maximize our entire incretin portfolio. Trulicity has established a strong market position. And I think the best data to support that is just how we've been able to grow share of market in the face of Ozempic and Rybelsus. So it has a strong position in the marketplace and that will remain.

克里斯，謝謝你的提問。不，tirzepatide 的結果並沒有改變我們想要在市場上定位 tirzepatide 的方式。顯然對這些結果非常滿意。我們也很幸運擁有 Trulicity 和 tirzepatide。我們的目標是最大化我們的整個腸促胰島素產品組合。 Trulicity 已經建立了強大的市場地位。我認為支持這一點的最佳數據就是我們如何能夠在面對 Ozempic 和 Rybelsus 時增加市場份額。因此，它在市場上具有強大的地位，並且將繼續存在。

But now as we think about tirzepatide, the dual incretin mechanism, that GIP component is really a game changer. Dan went through the results, but we just haven't seen the ability to return to someone living with type 2 diabetes, whether they're late or early, someone with type 2 diabetes progression, back to normal A1C. In fact, we were able to get 50% to 60% people back, it's really incredible. Also weight loss at the highest dose, up to 14%. So when you just take a look at that and you take a look at the fact that 90% of people who live with type 2 diabetes are overweight or obese, they can really benefit from early treatment with type 2 diabetes.

但現在當我們想到 tirzepatide，雙重腸促胰島素機制時，GIP 成分確實是遊戲規則的改變者。丹檢查了結果，但我們只是沒有看到讓患有 2 型糖尿病的人恢復到正常 A1C 的能力，無論他們是遲到還是早，患有 2 型糖尿病進展的人。事實上，我們能夠讓 50% 到 60% 的人回來，這真是不可思議。在最高劑量下體重減輕，高達 14%。因此，當您只看一眼這一事實時，您會看到 90% 的 2 型糖尿病患者超重或肥胖的事實，他們確實可以從 2 型糖尿病的早期治療中受益。

So the real question is why would you want to put them on something else early on? And why would you want to wait for them to have those benefits? So we see tirzepatide has the potential to really transform the market, driving earlier use of incretin, in particular tirzepatide's dual mechanism, and really expand the incretin market. So I think tirzepatide will clearly win some new patients that would have went on to Trulicity. You have some people who were maybe not performing well or not -- or needed more efficacy that will go on to tirzepatide. But clearly, our focus will be to profoundly change and disrupt the type 2 diabetes marketplace by driving earlier use of incretins with tirzepatide.

所以真正的問題是你為什麼要在早期把它們放在其他東西上？你為什麼要等待他們獲得這些好處？所以我們看到tirzepatide有潛力真正改變市場，推動腸促胰島素的早期使用，特別是tirzepatide的雙重機制，真正擴大腸促胰島素市場。所以我認為 tirzepatide 顯然會贏得一些本來會繼續使用 Trulicity 的新患者。有些人可能表現不佳或表現不佳 - 或者需要更多功效才能繼續使用 tirzepatide。但很明顯，我們的重點將是通過推動早期使用腸促胰島素和替西帕肽來深刻改變和擾亂 2 型糖尿病市場。

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

我們的下一個問題來自美國銀行的 Geoff Meacham。

Also have 2 pipeline ones. Just want to get your perspective on mirikizumab, the decision to focus on just IBD. You have good head-to-head data in psoriasis. So is it more of a commercial focus? Or is it that you want to focus more on Taltz and psoriasis? And then in Alzheimer's, you'll have zagotenemab data in the second half of this year. How are you thinking about the opportunity to combine potentially with donanemab? I wasn't sure what steps need to happen prior to thinking about that type of trial? And maybe from a regulatory perspective, what do you think would be a gating factor?

還有2個管道。只是想了解一下您對 mirikizumab 的看法，即只關注 IBD 的決定。您在牛皮癬方面擁有良好的面對面數據。那麼它更多的是商業焦點嗎？還是您想更多地關注 Taltz 和牛皮癬？然後在阿爾茨海默病中，您將在今年下半年獲得 zagotenemab 數據。您如何看待與 donanemab 潛在結合的機會？在考慮這種類型的試驗之前，我不確定需要採取哪些步驟？也許從監管的角度來看，你認為什麼是一個門控因素？

Thanks, Geoff. We'll go to Ilya for the first question and then Dan for the question on Alzheimer's.

謝謝，傑夫。我們將向 Ilya 提出第一個問題，然後向 Dan 提出關於阿爾茨海默氏症的問題。

Great. Geoff, thank you for the question. On mirikizumab, really as we see the greatest opportunity for unmet need for patients and we've said all along, we believe that mirikizumab has the greatest opportunity in GI, in IBD, in ulcerative colitis and Crohn's disease. We were pleased with the LUCENT-1 results. And so we're looking forward to seeing the maintenance data at the early part of next year.

偉大的。傑夫，謝謝你的問題。關於 mirikizumab，真的正如我們看到患者未滿足需求的最大機會並且我們一直說的那樣，我們相信 mirikizumab 在 GI、IBD、潰瘍性結腸炎和克羅恩病中具有最大的機會。我們對 LUCENT-1 的結果感到滿意。因此，我們期待在明年年初看到維護數據。

In terms of psoriasis, as we take a look at the market and unmet need, we do continue to believe that Taltz is the gold standard and best in disease and believe that really is a market well served. And so the decision from a portfolio standpoint is to focus our efforts in places where we believe we can have the greatest unmet need. And GI is where we're focused for mirikizumab.

就銀屑病而言，當我們審視市場和未滿足的需求時，我們確實繼續相信 Taltz 是黃金標準，是治療疾病的最佳選擇，並相信這確實是一個服務良好的市場。因此，從投資組合的角度來看，我們的決定是將我們的努力集中在我們認為可以滿足最大需求的地方。 GI 是我們專注於 mirikizumab 的地方。

Thanks, Ilya. Dan?

謝謝，伊利亞。擔？

Yes. Thanks, Geoff, for the question on zagotenemab, our anti-tau antibody. Before I come to combinations, maybe I'd just handicap this Phase II trial quickly. The pro here in favor of tau is clearly genetic validation and pathologic validation of the target. It's a great target for Alzheimer's disease. The cons here that we have to acknowledge is data from other companies' tau antibodies, which hasn't been particularly promising, and the difficulty in hitting the tau target in the brain. Now we have a differentiated antibody here that binds just aggregated tau, so perhaps there's reason to think we could get different results.

是的。謝謝，Geoff，關於我們的抗 tau 抗體 zagotenemab 的問題。在我開始組合之前，也許我會很快阻礙這個 II 期試驗。這裡支持 tau 的優勢顯然是目標的基因驗證和病理學驗證。它是阿爾茨海默病的一個很好的目標。我們必須承認的缺點是來自其他公司的 tau 抗體的數據，這並不是特別有希望，而且很難達到大腦中的 tau 目標。現在我們在這裡有了一種分化的抗體，它只結合聚集的 tau，所以也許有理由認為我們可以獲得不同的結果。

We're certainly eagerly awaiting those data in the second half of the year. And you're exactly right, if we see efficacy, combination would be an important consideration here. For sure, the general theme of combining an anti-amyloid drug with an anti-tau drug is a good one, particularly when you have a drug like donanemab, where you can completely clear amyloid plaques with a limited duration of therapy and then perhaps at that moment, intervene with an anti-tau drug. I do think that's the future. It's something we're actively considering, pending, of course, data on the tau antibody.

我們當然急切地等待下半年的這些數據。你說得對，如果我們看到療效，組合將是一個重要的考慮因素。可以肯定的是，將抗澱粉樣蛋白藥物與抗 tau 藥物聯合使用是一個很好的主題，特別是當您使用多那奈單抗這樣的藥物時，您可以在有限的治療時間內完全清除澱粉樣蛋白斑塊，然後可能在那一刻，用抗 tau 藥物進行干預。我確實認為這就是未來。這是我們正在積極考慮的事情，當然還有關於 tau 抗體的數據。

Our next question comes from Vamil Divan with Mizuho Securities.

我們的下一個問題來自瑞穗證券的 Vamil Divan。

Maybe one on Taltz. Maybe just a little more clarity or color on the pricing dynamics there. You mentioned you're kind of expecting a return to net sales growth in the second quarter and then accelerating. I'm just trying to think about it as we think about the full year dynamics. I don't know if you'll give product-level guidance. But how do you think about sort of the kind of full year comparison for 2021 to 2020? I assume you're still expecting growth for the year as a whole, but if you could just sort of clarify.

也許在 Taltz 上有一個。也許只是對那裡的定價動態更加清晰或色彩。你提到你有點期待第二季度的淨銷售額增長會恢復，然後會加速。我只是想在我們考慮全年動態時考慮它。我不知道您是否會提供產品級別的指導。但是，您如何看待 2021 年至 2020 年的全年比較？我假設你仍然期待全年的增長，但如果你能澄清一下。

And is that contract with ESI, I'm not sure, is that a full year contract? Or does that go beyond 1 year? I'm just trying to get a sense of sort of pricing dynamics in 2022 and 2023 and if we should expect another step-down. And then one quick follow-up just on the comments around TRAILBLAZER-3. I don't know if you can maybe just share a little more in terms of the number of patients you're looking to enroll in that trial, just so we can kind of get a sense of how long the enrollment might actually take.

我不確定與 ESI 的合同是否是全年合同？還是超過1年？我只是想了解 2022 年和 2023 年的定價動態，以及我們是否應該期待再次降級。然後對 TRAILBLAZER-3 周圍的評論進行快速跟進。我不知道您是否可以就您希望參加該試驗的患者數量多分享一點，這樣我們就可以了解註冊實際上可能需要多長時間。

Thanks, Vamil. We'll go to Ilya for the question on Taltz and kind of the full year picture and then Dan on TRAILBLAZER-3.

謝謝，瓦米爾。我們將向 Ilya 詢問有關 Taltz 的問題和全年的照片，然後是 TRAILBLAZER-3 的 Dan。

Sure. So on Taltz, first, let me just say we're really pleased about the progress we're making on Taltz and the growth that we're seeing with the step-up in access upgrades, ESI and beyond. And so as we take a look, even though that we've had some price impact in Q1, there are some elements there where we have a number of patients that were on medical exception that are now in the rebated contract that we have with ESI. Of course, we're also seeing an increase in overall volumes with ESI. What's encouraging is that we're not only seeing improvements in overall volume based off of switches, we're also seeing significant improvement in our new therapy starts.

當然。所以在 Taltz 上，首先，我只想說，我們對 Taltz 取得的進展以及我們在訪問升級、ESI 及其他方面所看到的增長感到非常高興。因此，當我們看一看，儘管我們在第一季度對價格產生了一些影響，但仍有一些因素使我們有一些醫療例外的患者現在在我們與 ESI 簽訂的回扣合同中.當然，我們也看到 ESI 的整體銷量有所增加。令人鼓舞的是，我們不僅看到基於開關的整體體積有所改善，而且我們還看到我們的新療法開始有了顯著改善。

And so we're, in dermatology, now the leading share in dermatology with over 19% share. And then in rheumatology, we're almost doubling our share from previous year. And so as we think about the year in terms of growth, we do believe we'll get to net sales growth in Q2, and we'll continue to accelerate that volume growth throughout the year. The contracting that we have for Taltz is -- goes beyond 1 year. And so we're encouraged about the volume growth of over 20% now, and we continue to see encouraging signs in the market.

因此，在皮膚病學領域，我們現在以超過 19% 的份額在皮膚病學領域處於領先地位。然後在風濕病學方面，我們的份額幾乎是去年的兩倍。因此，當我們從增長的角度考慮這一年時，我們確實相信我們將在第二季度實現淨銷售額增長，並且我們將在全年繼續加速銷量增長。我們與 Taltz 簽訂的合同超過 1 年。因此，我們對現在超過 20% 的銷量增長感到鼓舞，並且我們繼續在市場上看到令人鼓舞的跡象。

Thanks, Ilya. Dan?

謝謝，伊利亞。擔？

Yes. Thanks, Vamil, for the question on TRAILBLAZER-3 and our enrollment goals here. We probably don't get into too many details here, but we are, of course, expecting to -- this to be a large trial involving thousands of individuals, but yet we also set very ambitious enrollment goals. And while we don't have all the details planned out on how to achieve this, our goal is that we should be able to enroll this trial in about a year. That's pretty exciting to contemplate.

是的。感謝 Vamil 提出關於 TRAILBLAZER-3 的問題以及我們的招生目標。我們可能不會在這裡討論太多細節，但我們當然希望——這是一項涉及數千人的大型試驗，但我們也設定了非常雄心勃勃的招生目標。雖然我們還沒有計劃好如何實現這一目標的所有細節，但我們的目標是我們應該能夠在大約一年內參加這項試驗。這很令人興奮。

And Alzheimer's prevention trial is something that makes great sense, given the science and the biology here and what we know about the onset of Alzheimer's disease and its relation to years of having amyloid plaque in the brain. But there have been 2 major drawbacks that have not made these trials really very practical. First is finding the patients. That has gone from impossible before our introduction of amyloid PET scan to possible but really hard with amyloid PET scans as we experienced firsthand in the A4 trial to now something that's eminently feasible with our advent of the plasma tau -- phospho-tau217 assay. That's a huge advance that just unlocks this trial.

考慮到這裡的科學和生物學以及我們對阿爾茨海默病發病及其與大腦中澱粉樣斑塊多年的關係的了解，阿爾茨海默病預防試驗是非常有意義的。但是有兩個主要缺點並沒有使這些試驗真正非常實用。首先是尋找病人。這已經從我們引入澱粉樣蛋白 PET 掃描之前的不可能變為可能，但對於澱粉樣蛋白 PET 掃描來說真的很難，因為我們在 A4 試驗中親身體驗到現在隨著血漿 tau - phospho-tau217 檢測的出現而變得非常可行。這是一個巨大的進步，剛剛解鎖了這個試驗。

The second is if you think about this population, which is not experiencing symptoms, is a bit younger than an Alzheimer's population and introducing a therapy that is likely an infusion that they take for the rest of their lives, that's also a pretty significant hurdle. Again, we've, I think, abrogated that risk with donanemab in a limited treatment duration to give lasting plaque clearance, so excited about the TRAILBLAZER-3 trial.

第二個是，如果您考慮到這個沒有出現症狀的人群比阿爾茨海默氏症人群年輕一些，並且引入一種可能會在他們的餘生中接受的治療，這也是一個相當大的障礙。同樣，我認為，我們已經在有限的治療時間內消除了多納奈馬的風險，以提供持久的斑塊清除，對 TRAILBLAZER-3 試驗感到非常興奮。

Our next question comes from Seamus Fernandez with Guggenheim.

我們的下一個問題來自古根海姆的 Seamus Fernandez。

So just, first off, a question for Dave. Dave, as you think about some of the various proposals that are in Congress currently, could you just give us your thoughts on the tax proposal? And maybe Anat could give a little bit of the potential implications for Lilly. And then separately, there's obviously a lot of controversy swelling on drug pricing. Just wanted to get your sense of the proposals that are out there currently and if the industry is poised to or ready to step up with a more reasonable proposal.

所以，首先，問戴夫的一個問題。戴夫，當您考慮目前在國會提出的一些各種提案時，您能否就稅收提案給我們您的想法？也許 Anat 可以為禮來提供一些潛在影響。另外，藥品定價顯然存在很多爭議。只是想了解一下目前存在的提案，以及行業是否準備好或準備好提出更合理的提案。

And then just the second question is on the JAK inhibitor space and Lilly's opportunity with lebrikizumab, particularly in atopic dermatitis. There's a bit of a compare and contrast. Only Lilly, I think, has both potential opportunities in this space. I think there's a lot of speculation that there is going to be a safety update from the FDA, if not a full safety panel. Hoping, Dan, that you could give us a little bit of your thoughts in that regard.

然後第二個問題是關於 JAK 抑製劑領域和禮來公司使用 lebrikizumab 的機會，特別是在特應性皮炎方面。有一點比較和對比。我認為，只有禮來在這個領域擁有這兩個潛在機會。我認為有很多人猜測，如果不是完整的安全小組，FDA 將會進行安全更新。希望，丹，你能在這方面給我們一些你的想法。

Thanks, Seamus, lots to unpack there. We'll start with Dave on some of the policy, maybe Anat on the tax piece of that. And then we'll go to Ilya on kind of what he sees from a JAK and lebrikizumab standpoint.

謝謝，Seamus，有很多東西要打開。我們將從戴夫開始談一些政策，也許是阿納特談稅收。然後我們將討論 Ilya 從 JAK 和 lebrikizumab 的角度所看到的內容。

Yes, Seamus. Look, on tax, this is a live discussion, of course, because the president has introduced a number of ideas on corporate tax changes. I guess we join a growing chorus of large companies who oppose, that means to raise revenue, especially when the stated policy goal of the infrastructure plan is to build back the economy. Of course, private money and corporate actions make up the vast majority of the investment that could or would occur. And taxing that seems like a bad idea, maybe the opposite idea from the bill itself.

是的，西莫。看，關於稅收，這是一個現場討論，當然，因為總統已經介紹了一些關於公司稅收變化的想法。我想我們加入了越來越多的反對大公司的行列，這意味著增加收入，特別是當基礎設施計劃的既定政策目標是重建經濟時。當然，私人資金和公司行為構成了可能或將要發生的絕大多數投資。徵稅似乎是個壞主意，也許與法案本身相反。

Within the bill, maybe just a couple of general comments, and we can follow up if we need to. There's the nominal rate discussion, which, of course, when we say moving from 21% to 28% is moving toward the middle of the pack, is not true because, of course, in the U.S., we have state-level income tax. It would really put the U.S. at the highest developed economy in terms of corporate tax rate.

在該法案中，可能只是一些一般性評論，如果需要，我們可以跟進。有名義稅率的討論，當然，當我們說從 21% 到 28% 正在向中間移動時，這是不正確的，因為當然，在美國，我們有州級所得稅。就公司稅率而言，這確實會使美國成為最高的發達經濟體。

Additionally, we're the only major economy that taxes overseas earnings of its domiciled companies and changing the so-called GILTI tax, foreign minimum tax, really is punitive to our home companies in multiple ways and is something that would have a disproportionate effect on pharmaceutical companies. And so both these actions don't make a lot of sense to us and we oppose. We would favor things like looking at funding the IRS, so they can collect taxes from all the people that don't pay, including businesses and other items that could be pay-fors, we certainly support infrastructure in many ways.

此外，我們是唯一對其註冊公司的海外收入徵稅的主要經濟體，並改變所謂的 GILTI 稅，即外國最低稅，實際上以多種方式對我們的母國公司造成懲罰，並且會產生不成比例的影響製藥公司。所以這兩種行為對我們來說都沒有多大意義，我們反對。我們更傾向於為 IRS 提供資金，這樣他們就可以向所有不繳稅的人徵收稅款，包括企業和其他可以付費的項目，我們當然會以多種方式支持基礎設施。

On drug pricing, this has been pushed out a little bit. I wouldn't be surprised if we see HR 3 being debated soon, but as you may have read, apparently it won't be part of the second package from the White House. That's good because HR 3 and those concepts are really set to take a huge piece out of the industry, do nothing for patient out-of-pocket affordability and really derail the innovation machine that is the only reason we're escaping from the COVID-19 pandemic. So we will oppose that with every ounce of our being as pharma.

在藥品定價方面，這已經被推遲了一點。如果我們很快看到 HR 3 被討論，我不會感到驚訝，但正如你可能已經讀到的，顯然它不會成為白宮第二個方案的一部分。這很好，因為 HR 3 和這些概念確實將在行業中佔據一席之地，對患者的自付費用無能為力，並真正破壞創新機器，這是我們逃離 COVID- 的唯一原因- 19 流行病。因此，作為製藥商，我們將竭盡全力反對這一點。

That said, we are all for changes to the system that make out-of-pocket costs go down for patients. There are a lot of ways to do this within the system that the industry is willing to put pay-fors on the table. This is much more around the contours of maybe what we saw with Senate Finance or the reported proposals made in the 11th hour of the last administration. We will table those ideas. We are tabling those ideas. And I think probably in the second half, you'll hear more about that.

也就是說，我們都支持改變系統，降低患者的自付費用。在業界願意付出代價的系統中有很多方法可以做到這一點。這更接近於我們在參議院財政方面看到的情況或上屆政府第 11 小時提出的報告提案。我們將列出這些想法。我們正在提出這些想法。我想可能在下半年，你會聽到更多關於這個的消息。

We think there's a great opportunity to improve affordability and strengthen the health care system and really address health care inequities as well that occur because people who are of lower economic means, people of color, women are disproportionately affected by bad insurance design and bad benefit design. We can shore those up and make the health care system work better for everyone.

我們認為這是一個很好的機會來提高負擔能力和加強醫療保健系統，並真正解決由於經濟能力較低的人、有色人種、女性受到不良保險設計和不良福利設計的影響而發生的醫療保健不平等現象.我們可以支持這些，讓醫療保健系統更好地為每個人服務。

Thanks, Dave. Ilya?

謝謝，戴夫。伊利亞？

Yes. Seamus, so thank you for the question. As you noted and what we said on the call is that we're quite excited about our progress in immunology as a whole. And if we think about the growth opportunities within immunology, atopic dermatitis is one catalyst for the company, both in what we believe in Olumiant's success but also lebrikizumab. In terms of the question around JAKs and FDA decision, I won't speculate on any decision the FDA may make. But it's safe to say that the delay across all JAKs in atopic dermatitis and other indications suggests that there's a broader review on JAK safety. We feel that Olumiant has a robust safety profile. And with dermatology being more safety conscious, we do believe that Olumiant has a very good prospect to compete in this space, especially after topical failure.

是的。 Seamus，謝謝你的提問。正如您所指出的以及我們在電話會議上所說的是，我們對我們在整個免疫學方面的進展感到非常興奮。如果我們考慮免疫學領域的增長機會，特應性皮炎是該公司的催化劑之一，無論是我們相信 Olumiant 的成功，還是 lebrikizumab。關於 JAK 和 FDA 決定的問題，我不會推測 FDA 可能做出的任何決定。但可以肯定地說，特應性皮炎和其他適應症中所有 JAK 的延遲表明對 JAK 安全性進行了更廣泛的審查。我們認為 Oluminant 具有強大的安全性。而且隨著皮膚科的安全意識越來越強，我們相信 Olumiant 在這個領域有很好的競爭前景，尤其是在局部失敗之後。

And then lebrikizumab is one to watch out for, for the second half of the year. As we get more data, well, we feel like we can compete and differentiate versus Dupixent. And so long-term prospect and catalysts for growth are very good for having both mechanisms. And we also see catalyst for growth in alopecia areata, a very -- to be first in disease with Olumiant. And so we feel very good about our chances to not only compete but also to have significant growth and have meaningful outcomes for patients.

然後 lebrikizumab 是今年下半年值得關注的一個。隨著我們獲得更多數據，我們覺得我們可以與 Dupixent 競爭和區分。因此，這兩種機制的長期前景和增長催化劑都非常好。我們還看到了斑禿增長的催化劑，這是一種非常 - 第一個使用 Olumiant 治療的疾病。因此，我們對我們不僅有機會競爭而且有顯著增長並為患者帶來有意義的結果感到非常高興。

Our next question comes from the line of Louise Chen with Cantor.

我們的下一個問題來自於 Cantor 的 Louise Chen 的台詞。

So first question I had for you was on lebrikizumab. What do you think will differentiate your products from others that are already approved and those in development? And do you plan to pursue lebrikizumab for any other indications? And then second question is on LOXO-305 plus LOXO-338. What do you think your competitive advantages are here versus others that are trying to do the same thing?

所以我問你的第一個問題是關於lebrikizumab。您認為您的產品與其他已獲批准和正在開發的產品有何不同？您是否計劃針對任何其他適應症尋求 lebrikizumab？然後第二個問題是關於 LOXO-305 和 LOXO-338。您認為與其他試圖做同樣事情的人相比，您的競爭優勢是什麼？

Great. Thanks, Louise. We'll go to Ilya for the first question and Jake for the second.

偉大的。謝謝，路易絲。第一個問題我們去找 Ilya，第二個問題找 Jake。

Yes. Louise, thank you for the question about lebrikizumab. In terms of area differentiation, the focus for lebrikizumab is not only to look at the efficacy on skin but also one of the more impactful symptoms related to atopic dermatitis is itch. And so we believe we may have the opportunity to differentiate on itch, which also has impact on sleep. And we believe that lebrikizumab may have a better safety profile. So that's where we believe we can differentiate. And so we're excited to get the results for lebrikizumab at the back half of the year. In terms of new indications, I think it's early to take a look at any new indications. We're obviously evaluating opportunities to grow lebrikizumab. But our full focus right now is making sure we have success in atopic dermatitis.

是的。路易絲，感謝您提出有關 lebrikizumab 的問題。就區域區分而言，lebrikizumab 的重點不僅在於查看對皮膚的功效，而且與特應性皮炎相關的影響更大的症狀之一是瘙癢。因此，我們相信我們可能有機會區分瘙癢，這也會對睡眠產生影響。我們相信 lebrikizumab 可能具有更好的安全性。所以這就是我們相信我們可以區分的地方。因此，我們很高興能在今年下半年獲得 lebrikizumab 的結果。在新的適應症方面，我認為現在看任何新的適應症還為時過早。我們顯然正在評估發展 lebrikizumab 的機會。但我們現在的全部重點是確保我們在特應性皮炎方面取得成功。

Ilya, just to jump in on top of that, of course, there will be a dosing convenience and dosing certainty benefit with lebri as well.

Ilya，當然，最重要的是，lebri 也會有給藥方便和給藥確定性的好處。

Thanks. Jake?

謝謝。傑克？

Thanks for the question, Louise, about pirtobrutinib, LOXO-305 and LOXO-338, the BCL-2 inhibitor. I think as it relates to differentiation, I'd point out a few things. First off, obviously, as I think you and others know, pirtobrutinib itself is a differentiated BTK inhibitor that we believe affords certain advantages in combination. Obviously, we need to prove that clinically, but that's our hypothesis right now. So that sort of stands on its own. The LOXO-338 program, the BCL-2 inhibitor, we'll be putting into the clinic this year. And obviously, important that, that drug meets its human pharmacology goals so that we know that it itself is on track as a drug. Should that prove to be the case, which we expect it to, we will then look to combine these 2 agents.

感謝 Louise 提出關於 pirtobrutinib、LOXO-305 和 LOXO-338（BCL-2 抑製劑）的問題。我認為由於它與差異化有關，我會指出一些事情。首先，很明顯，正如我想你和其他人都知道的那樣，pirtobrutinib 本身是一種差異化的 BTK 抑製劑，我們認為它在組合中具有一定的優勢。顯然，我們需要在臨床上證明這一點，但這是我們現在的假設。所以那種立場是獨立的。 LOXO-338 計劃，BCL-2 抑製劑，我們將在今年投入臨床。顯然，重要的是，該藥物符合其人類藥理學目標，因此我們知道它本身作為一種藥物正在走上正軌。如果事實證明是這樣，我們期望它，然後我們將考慮合併這兩個代理。

I think when you look out at others that are combining BTK and BCL-2, the latter largely being venetoclax, I think what you see is a very fragmented landscape of asset ownership across companies, and as a result of that, some -- oftentimes perverse incentives about how to combine those drugs and where. We think it's important that if you have a new and differentiated BTK inhibitor like we believe we do with pirtobrutinib, we thought it was strategically important to own our own BCL-2 inhibitor. And so we think we'll be really the only player in the field who owns both agents outright. So that, to us, is a key differentiating feature downstream. But it's still a bunch of hoops we have to jump through to enable that combination.

我認為，當您查看其他結合 BTK 和 BCL-2（後者主要是 venetoclax）的公司時，我認為您看到的是跨公司資產所有權非常分散的格局，因此，一些 - 經常關於如何組合這些藥物以及在何處組合的不正當激勵措施。我們認為重要的是，如果您有一種新的、差異化的 BTK 抑製劑，就像我們相信我們對 pirtobrutinib 所做的那樣，我們認為擁有我們自己的 BCL-2 抑製劑具有戰略意義。所以我們認為我們將成為該領域唯一一個完全擁有這兩名經紀人的球員。因此，對我們來說，這是下游的一個關鍵差異化特徵。但它仍然是一堆我們必須跳過才能實現這種組合的箍。

Next, we go to the line of Carter Gould with Barclays.

接下來，我們與 Barclays 一起去 Carter Gould 的路線。

All right. I guess, first, for Dan or Mike, you guys posted details of the SUMMIT study of tirzepatide and HFpEF recently. And I think the design, size and time line were all surprising relative to expectations, so I guess getting to a readout much faster than some have had expected. Can you maybe just walk through some of those key design choices and the extent regulators have bought in, and also confirm that that single study would be sufficient for approval in that setting? And then also historically, Lilly has done a -- I think, done a better job of sort of franchise building in certain areas than some of its peers. Now with sort of mirikizumab derisking data, can you talk around how you're thinking about building around the GI portfolio?

好的。我想，首先，對於 Dan 或 Mike，你們最近發布了關於 tirzepatide 和 HFpEF 的 SUMMIT 研究的詳細信息。而且我認為設計、尺寸和時間線都相對於預期令人驚訝，所以我想讀取速度比一些人預期的要快得多。您是否可以僅介紹其中一些關鍵設計選擇以及監管機構的購買程度，並確認單項研究足以在那種情況下獲得批准？然後從歷史上看，禮來公司在某些領域的特許經營建設方面做得比一些同行做得更好。現在有了一些 mirikizumab derisking 數據，你能談談你是如何考慮圍繞 GI 產品組合構建的嗎？

Thanks, Carter. We'll go to Mike for the question on tirzepatide and Ilya for the question on miri.

謝謝，卡特。我們將向 Mike 詢問關於 tirzepatide 的問題和 Ilya 詢問關於 miri 的問題。

Yes. Thanks for the question on the SUMMIT trial. We're bullish on the opportunity for tirzepatide in HFpEF. When you look at that, it's really a large unmet need with nearly 4 million people living with HFpEF heart failure, a leading cause of hospitalization in the U.S. When you look at it scientifically, you do see that there is a [BC-related] HFpEF phenotype that we believe that tirzepatide can play a large role in helping out. And so that's what really drove our investment in SUMMIT. And I think the team has done a nice job of coming up with a creative approach that will provide, I think, robust data for payers and clinicians to make that decision. So I think we're very confident in this -- in both our clinical trial design as well as the commercial opportunity.

是的。感謝您提出關於 SUMMIT 試驗的問題。我們看好 HFpEF 中 tirzepatide 的機會。當你看到這一點時，這確實是一個巨大的未滿足需求，有近 400 萬人患有 HFpEF 心力衰竭，這是美國住院的主要原因。當你從科學的角度看待它時，你確實看到有 [BC-related] HFpEF 表型，我們認為替西帕肽可以起到很大的幫助作用。這就是我們對 SUMMIT 投資的真正推動力。而且我認為該團隊在提出一種創造性的方法方面做得很好，我認為該方法將為付款人和臨床醫生提供可靠的數據以做出決定。所以我認為我們對此非常有信心——無論是臨床試驗設計還是商業機會。

Thanks, Mike. We'll go to Ilya for the next answer.

謝謝，邁克。我們將去伊利亞尋求下一個答案。

Sure. Yes, Carter, listen, as you noted, in terms of building franchises across immunology, we've built up our scale in dermatology and excited about increasing number of treatments there, the same with rheumatology in the hope for finding lupus as well. And then in GI, mirikizumab will be our first entrant into GI with ulcerative colitis and Crohn's disease. And then we do have a pretty robust pipeline in both Phase I and proof-of-concept studies, in particular, IL-2 conjugate that we're studying for ulcerative colitis as well. And we look forward to bringing out new treatments across all 3 of those areas in the coming years.

當然。是的，卡特，聽著，正如你所說，在建立免疫學專營權方面，我們已經擴大了皮膚病學的規模，並對那裡越來越多的治療感到興奮，風濕病學也是如此，希望也能找到狼瘡。然後在 GI 中，mirikizumab 將成為我們第一個進入 GI 的潰瘍性結腸炎和克羅恩病患者。然後，我們在 I 期和概念驗證研究中確實有一個非常強大的管道，特別是我們正在研究潰瘍性結腸炎的 IL-2 偶聯物。我們期待在未來幾年在所有這三個領域推出新的治療方法。

Our next question comes from Tim Anderson with Wolfe Research.

我們的下一個問題來自 Wolfe Research 的 Tim Anderson。

A couple of questions. On Verzenio and the CDK class more broadly. Can you talk about what you're seeing in the U.S. in terms of rebating for this oral oncology category? My understanding is that the level of rebates may be stepping up. And I'm not sure which company or companies are driving that. Maybe it's Pfizer driving that as they try to hang on to market share. But what's the outlook for gross-to-net price trends in this category?

幾個問題。關於 Verzenio 和更廣泛的 CDK 類。你能談談你在美國看到的關於這個口腔腫瘤學類別的回扣嗎？我的理解是，回扣的水平可能會提高。我不確定是哪家公司或哪家公司在推動這一點。也許是輝瑞在努力保持市場份額時推動了這一點。但這一類別的毛淨價趨勢前景如何？

And then on Tyvyt, your PD-1 from Innovent, a Chinese company, you note that you'll file for approval in non-small cell lung in the U.S. this year. It's really hard for me to see how you gain any share with this product, given what would be a limited label and given payer and prescriber dynamics, where in things like Part B, you can't really compete on price. So what's realistic to expect with this product from a commercial perspective, not only U.S. but in other Western markets like Europe?

然後在 Tyvyt，您來自中國公司 Innovent 的 PD-1，您注意到您今年將在美國申請非小細胞肺的批准。考慮到有限的標籤以及付款人和開藥人的動態，我很難看到您如何從該產品中獲得任何份額，在 B 部分之類的情況下，您無法真正在價格上競爭。那麼，從商業角度來看，這種產品的實際期望是什麼，不僅是美國，而且在歐洲等其他西方市場？

Thanks, Tim. We'll go to Anne White for both of those.

謝謝，蒂姆。我們將為這兩個去安妮懷特。

Well, thanks, Tim, for the question on Verzenio. So I think, as you're mentioning, it's an incredibly competitive market with the CDK4/6s. And so we and others continue to do what we need to do to make sure that patients get access to the right medicines. So we have obviously a strong strategy there. I can't comment on the specifics, but we do see competition. And really, what we're seeing -- I think you're seeing in Verzenio, what we're seeing is an incredibly nice trend growing in Q1.

好吧，謝謝蒂姆，關於 Verzenio 的問題。所以我認為，正如你所提到的，CDK4/6s 是一個極具競爭力的市場。因此，我們和其他人繼續做我們需要做的事情，以確保患者能夠獲得正確的藥物。所以我們顯然有一個強有力的戰略。我無法評論具體細節，但我們確實看到了競爭。真的，我們所看到的——我認為你在 Verzenio 看到的是，我們看到的是第一季度增長的令人難以置信的好趨勢。

As you saw, we had positive momentum with the U.S. strong share growth in March and we saw TRx of over 17% and NBRx of over 28%, so -- and this is despite, as you've noticed, a modest year-on-year TRx market decline. So I think what we're seeing is both from a payer strategy but also very much from a data strategy, we're seeing that Verzenio is growing its share nicely. And so I like how all of our different programs are coming together.

正如你所看到的，我們在 3 月份強勁的美國股市增長勢頭強勁，我們看到超過 17% 的 TRx 和超過 28% 的 NBRx，所以 - 儘管你已經註意到，這是一個溫和的年- 年 TRx 市場下滑。因此，我認為我們所看到的既來自支付者策略，也來自數據策略，我們看到 Verzenio 正在很好地增長其份額。所以我喜歡我們所有不同的項目如何結合在一起。

And obviously, the data in adjuvent breast cancer reinforce the growing awareness that these medicines are different. But what really has been the focus for our execution has been capitalizing on positive OS data and making sure that people are aware of that and we're seeing more trial, more adoption as we go through that. So very pleased how all of our strategies with Verzenio are coming together.

顯然，輔助乳腺癌的數據加強了人們對這些藥物不同的認識。但是，我們執行的真正重點是利用積極的操作系統數據並確保人們意識到這一點，我們正在看到更多的試驗和更多的採用。非常高興我們與 Verzenio 的所有策略如何結合在一起。

On Tyvyt, yes, I mean, as you mentioned, it's a competitive space, obviously. And while I can't really comment on our commercial strategy prior to approval, you can be reassured that we're looking at ways to differentiate and really add value to this innovative class of medicines. So obviously, we know that there's certain commercial approaches we'll have to take to capture share as really a late entrant in the field, but we see opportunity here.

在 Tyvyt 上，是的，我的意思是，正如你所提到的，這顯然是一個競爭空間。雖然在批准之前我不能真正評論我們的商業戰略，但您可以放心，我們正在尋找區分這種創新藥物並真正增加價值的方法。因此，很明顯，我們知道我們必須採取某些商業方法來獲得該領域真正的後進者的份額，但我們在這裡看到了機會。

And obviously, this deal made sense with the partnership that we've had with Innovent and we're committed to the U.S. submission this year. And so more to come as we look to launch the product and share that strategy and how we intend to make an opportunity here. But as you said, I wouldn't assess this as a large opportunity for Lilly, but an opportunistic one that we think makes sense, it makes sense for patients globally and driving value for them.

顯然，這筆交易對我們與 Innovent 的合作是有意義的，我們致力於今年在美國提交申請。當我們希望推出產品並分享該戰略以及我們打算如何在這裡創造機會時，還會有更多的事情發生。但正如你所說，我不會認為這對禮來公司來說是一個巨大的機會，而是一個我們認為有意義的機會主義機會，這對全球患者來說是有意義的，並為他們帶來了價值。

We'll move to the lightning round, so we can try to get everyone in. (Operator Instructions)

我們將進入閃電回合，這樣我們就可以嘗試讓每個人都參與進來。（操作員說明）

Next, we have Andrew Baum with Citi.

接下來是花旗的 Andrew Baum。

Yes, a question for Dan on Verzenio and the monarchE filing. As you outlined, the survival data is thankfully going to take a long time to mature. Is the answer that the FDA is looking for more about further maturation of progression-free survival or -- sorry, disease-free survival? Just given the historic precedence of the PENELOPE-B data with palbociclib, where you have separation that then coming together, isn't that really what the FDA wants, given if you're waiting for survival, you could be waiting for a very long time indeed?

是的，丹在 Verzenio 和 monarchE 文件上的問題。正如你所概述的，幸好生存數據需要很長時間才能成熟。 FDA 正在尋找更多關於無進展生存期或 - 抱歉，無病生存期的答案？考慮到 PENELOPE-B 數據與 palbociclib 的歷史優先級，在那裡你有分離然後聚集在一起，這不是 FDA 真正想要的，如果你正在等待生存，你可能會等待很長時間確實是時間？

Thanks, Andrew. Dan?

謝謝，安德魯。擔？

I'll just take it quickly. No, Andrew, it's -- the focus here is on the overall survival. On the distant relapse-free survival, as we commented, the curves are not coming together, they're actually separating more. It's improving as we get more events. So I'm not aware of any concerns around that.

我會盡快接受。不，安德魯，這是 - 這裡的重點是整體生存。正如我們所評論的那樣，在遙遠的無復發生存期，曲線並沒有融合在一起，它們實際上分離得更多。隨著我們獲得更多活動，情況正在改善。所以我不知道對此有任何擔憂。

Next, we go to the line of Steve Scala with Cowen.

接下來，我們與 Cowen 一起前往 Steve Scala。

I think it was stated that the number of CV events in SURPASS-4 has been reached, if I heard that correctly. If that's correct, then it looks like the study is going to achieve its endpoint earlier than expected. So my question is, is that either confidence-building or concerning? Are you worried COVID-19 cardiovascular effects may have impacted the accrual of events? And if tirzepatide trends worse than insulin glargine, can you still file?

如果我沒聽錯的話，我認為已經達到了 SURPASS-4 中的 CV 事件數量。如果這是正確的，那麼看起來這項研究將比預期更早地達到其終點。所以我的問題是，這是建立信任還是令人擔憂？您是否擔心 COVID-19 心血管效應可能會影響事件的發生？如果 tirzepatide 的趨勢比甘精胰島素更差，你還能申請嗎？

Thanks, Steve. We'll go to Mike on that.

謝謝，史蒂夫。我們會去找邁克的。

Yes. Thanks for the question. No, we have no concerns. We will -- we have reached the number we needed to complete the trial. We're getting patients back in. We'll have that data, should start to see top line in May, and we'll release that information in -- before the end of the quarter. We're very, very excited about tirzepatide and very confident in its CV profile. I'm looking forward to seeing the SURPASS-4 data.

是的。謝謝你的問題。不，我們不擔心。我們將——我們已經達到了完成試驗所需的數量。我們正在讓病人回來。我們將擁有這些數據，應該會在 5 月份開始看到頂線，我們將在本季度末之前發布這些信息。我們對 tirzepatide 感到非常非常興奮，並且對其 CV 資料非常有信心。我期待看到 SURPASS-4 數據。

Next, we go to the line of Terence Flynn with Goldman Sachs.

接下來，我們與高盛一起前往 Terence Flynn。

I was just wondering on monarchE, if there's any possibility of an NCCN listing before the FDA action? And then can you give us an update on the Retevmo launch dynamics this quarter?

我只是想知道 monarchE，是否有可能在 FDA 採取行動之前上市 NCCN？然後你能給我們介紹一下本季度 Retevmo 的發布動態嗎？

Thanks, Terence. We'll go to Anne for the question on Verzenio and Retevmo.

謝謝，特倫斯。關於 Verzenio 和 Retevmo 的問題，我們會去找 Anne。

Thanks for the question. So on monarchE and NCCN, I really can't comment for them. So obviously, we feel that this data is incredibly impactful. I think one of our thought leaders call it the most notable development in HER2-positive breast cancer in the last 2 decades, but we'll just have to wait and see what NCCN decides to do.

謝謝你的問題。所以在 monarchE 和 NCCN 上，我真的不能對他們發表評論。很明顯，我們認為這些數據具有難以置信的影響力。我認為我們的一位思想領袖稱其為過去 20 年來 HER2 陽性乳腺癌最顯著的發展，但我們只需要等待，看看 NCCN 決定做什麼。

And then on Retevmo, the launch is going well. So we had a virtual launch in May, we finished 2020 with $37 million in sales, and we see positive momentum in Q1. So we've had a great engagement with customers. Unaided brand awareness is strong. So we're quite pleased. And this is an incredibly important medicine, as you know, in some patients, over an 80% response rate, so great response from the customers. I'm very enthusiastic about what we're seeing so far.

然後在 Retevmo 上，發布進展順利。因此，我們在 5 月進行了虛擬發布，到 2020 年結束時的銷售額為 3700 萬美元，我們在第一季度看到了積極的勢頭。因此，我們與客戶進行了很好的互動。獨立的品牌意識很強。所以我們很高興。這是一種非常重要的藥物，如您所知，在某些患者中，反應率超過 80%，客戶反應非常好。我對我們目前所看到的非常感興趣。

Our next question comes from Ronny Gal with Bernstein.

我們的下一個問題來自 Ronny Gal 和 Bernstein。

So we are seeing you adopting cost-conscious strategies on both Taltz and on mirikizumab. And I was kind of wondering, if you're going to look forward 5 years, where do you see immunology pricing then goes in terms of dollars for you? It's right now in the low to mid-30s, the way we can see it. 5 years here from now, are we going be in the mid-20s, under 20, 30-plus? Where do you see the band of pricing looking like?

因此，我們看到您在 Taltz 和 mirikizumab 上都採用了注重成本的策略。我有點想知道，如果你要展望 5 年，你認為免疫學定價會以美元計算嗎？它現在處於 30 年代中期到 30 年代中期，我們可以看到它。從現在開始的 5 年，我們會在 20 多歲、20 歲以下、30 歲以上嗎？您在哪裡看到定價範圍？

Thanks, Ronny. We'll go to Ilya for questions on immunology pricing trends.

謝謝，羅尼。我們將前往 Ilya 詢問有關免疫學定價趨勢的問題。

Yes. Ronny, thanks for the question on immunology. In terms of our focus, it's -- let's not -- conscious is more related to looking at opportunities for growth. We have a long runway for Taltz. And so we do believe that Taltz is kind of at the foundation of our immunology strategy. We have numerous head-to-head studies in real world evidence to suggest that Taltz is a best-in-disease treatment. And as part of our growth strategy looking at mirikizumab in GI, we do believe that within the next 5 to 10 years, we can, across multiple mechanisms in those 3 specialized groups, dermatology, rheumatology and GI, have significant growth and become a top-tier immunology company. In terms of pricing, I think it's -- they're all very competitive fields. And so our goal is to have great evidence and create access opportunities for patients that need these treatments.

是的。 Ronny，感謝您提出關於免疫學的問題。就我們的關注點而言，它——我們不要——意識更多地與尋找增長機會有關。我們為 Taltz 準備了一條很長的跑道。因此，我們確實相信 Taltz 是我們免疫學戰略的基礎。我們在現實世界的證據中進行了大量的頭對頭研究，表明 Taltz 是一種最佳的疾病治療方法。作為我們在 GI 中研究 mirikizumab 的增長戰略的一部分，我們相信在未來 5 到 10 年內，我們可以通過皮膚病學、風濕病學和 GI 這三個專業組的多種機制實現顯著增長並成為頂級級免疫學公司。在定價方面，我認為它們都是非常有競爭力的領域。因此，我們的目標是獲得大量證據，並為需要這些治療的患者創造機會。

Next, we go to the line of Kerry Holford with Berenberg.

接下來，我們與貝倫伯格一起前往克里霍爾福德的路線。

Just on the COVID antibodies, I wonder if you can just discuss the disconnect between your lower 2021 term guidance and the higher associated R&D spend. And with that context, do you have a budget cap in mind for your ongoing COVID investments?

就 COVID 抗體而言，我想知道您是否可以討論一下您的 2021 年較低任期指導與較高的相關研發支出之間的脫節。在這種情況下，您是否為正在進行的 COVID 投資設定了預算上限？

Thanks, Kerry. We'll go to Anat for that.

謝謝，克里。我們將為此前往 Anat。

Sure. Thanks, Kerry. Let me start with the budget. So we did increase our guidance for the COVID antibody investment from $300 million to $400 million to $400 million to $500 million. And the investments that we've announced this morning is really to address the growth in variants that we see globally and looking at additional antibodies that could address that. The lowering on the high end of the range, really it relates to the changes you've seen here in the U.S. government as well as what we see globally in terms of progression of the disease, but -- and this is one I know that is more challenging to forecast, given that there's not a lot of TRx data or data for you to look at, and we'll continue to update obviously with every quarter.

當然。謝謝，克里。讓我從預算開始。因此，我們確實將 COVID 抗體投資的指導從 3 億美元增加到 4 億美元、4 億美元到 5 億美元。我們今天早上宣布的投資實際上是為了解決我們在全球範圍內看到的變體的增長，並尋找可以解決這個問題的其他抗體。範圍高端的降低，實際上與您在美國政府中看到的變化以及我們在全球範圍內看到的疾病進展有關，但是 - 這是我知道的鑑於沒有太多的 TRx 數據或數據可供您查看，因此預測更具挑戰性，而且我們將在每個季度明顯地繼續更新。

And maybe just to add as a mindset thing, we didn't get into this because we were thinking about margins or business profile, it was to be useful during the pandemic, which is still going on, obviously, raging in other parts of the world. One other driver for the top line is that increasingly, we'll be selling our products into lower-priced markets or giving it away because that's where the disease is. And when the pandemic period ends, I think we can then take a different look at this enduring business, but we're not there yet. So we're making the investments we need to, to be useful and selling the product where it's needed at the price structure we had previously announced, which is heavily discounted in low GDP markets.

也許只是為了補充一種心態，我們沒有進入這一點，因為我們正在考慮利潤或業務概況，它在大流行期間很有用，顯然，大流行仍在繼續，在其他地區肆虐世界。頂線的另一個驅動因素是，我們將越來越多地將我們的產品銷售到價格較低的市場或放棄它，因為那是疾病所在。當大流行期結束時，我認為我們可以對這個經久不衰的業務採取不同的看法，但我們還沒有做到。因此，我們正在進行我們需要的投資，以使產品變得有用，並以我們之前宣布的價格結構在需要的地方銷售產品，這在低 GDP 市場中大幅打折。

Next, we go to the line of Umer Raffat with Evercore.

接下來，我們與 Evercore 一起前往 Umer Raffat 的路線。

Dan, last we spoke in mid-March, it seems like you hadn't had a lot of regulatory discussions on donanemab, but it does feel like you've had them now. So I'm curious, the FDA feedback on the new endpoint, iADRS, as well as the Bayesian analysis. And also very briefly, on CD73, there's an interesting emerging signal in some of the other CD73s in pancreatic setting. I noticed you guys discontinued, would love to find out any additional color.

丹，上次我們是在 3 月中旬談過的，你似乎沒有對多納奈馬進行很多監管討論，但感覺你現在已經有了。所以我很好奇，FDA 對新端點 iADRS 以及貝葉斯分析的反饋。並且非常簡單地說，在 CD73 上，在胰腺環境中的其他一些 CD73 中有一個有趣的新興信號。我注意到你們停產了，很想找出任何其他顏色。

Thanks, Umer. Dan?

謝謝，烏默爾。擔？

Yes, sure. So FDA feedback is -- has been continuing, I should say. We had some and it continues to come. I think our view here is unchanged. We previously said that the FDA has concerns around iADRS because it combines cognition and function. And there's always a risk that you could have a positive signal on iADRS driven by cognition with no benefit on function or function going the other way or vice versa. And that wouldn't be acceptable for approval of a new drug. So that's the risk there. On the CD73 Phase I termination, I don't have additional comments.

是的，當然。所以 FDA 的反饋是 - 我應該說一直在繼續。我們有一些，而且還在繼續。我認為我們在這裡的觀點沒有改變。我們之前說過，FDA 對 iADRS 存在擔憂，因為它結合了認知和功能。並且總是存在這樣的風險，即您可能會在認知驅動的 iADRS 上獲得積極信號，而對功能沒有好處，或者功能相反，反之亦然。這對於批准一種新藥是不可接受的。所以這就是那裡的風險。關於 CD73 第一階段的終止，我沒有其他意見。

And last question comes from Gilbert with Truist Securities.

最後一個問題來自 Truist Securities 的吉爾伯特。

Dan, on tanezumab, is the outlook any more hopeful than the optics of the AdCom vote? And can you comment on where pain fits into your overall R&D priority list at this point?

Dan，在 tanezumab 上，前景是否比 AdCom 投票的結果更有希望？你能評論一下疼痛在你的整體研發優先列表中的位置嗎？

Sure. Gregg, thanks for the question. Pain is still a really important unmet medical need. Clearly, the regulatory bar is high here in terms of safety. And we saw that from the Tanezumab Advisory Committee meeting, which was a pretty decisive outcome there and one that we were disappointed in.

當然。格雷格，謝謝你的問題。疼痛仍然是一個非常重要的未滿足的醫療需求。顯然，就安全而言，這裡的監管門檻很高。我們從 Tanezumab 諮詢委員會會議上看到了這一點，這是一個非常決定性的結果，我們對此感到失望。

Thanks, Dan. Gregg, thanks for your question. Back to Dave for the close.

謝謝，丹。格雷格，謝謝你的問題。回到戴夫結束。

Okay. Thanks, Kevin. We appreciate your participation in today's call and your interest in Eli Lilly and Company. 2021 has been -- has begun with good momentum in our underlying business. We remain focused on executing our innovation-based strategy to bring new medicines to patients and create value for all our stakeholders. As we continue to scale our diverse commercial portfolio, complemented by a pipeline of industry-leading opportunities, we believe Lilly continues to be a compelling investment.

好的。謝謝，凱文。感謝您參加今天的電話會議以及您對禮來公司的興趣。 2021 年已經開始，我們的基礎業務勢頭良好。我們仍然專注於執行我們以創新為基礎的戰略，為患者帶來新藥，並為我們所有的利益相關者創造價值。隨著我們繼續擴大我們多樣化的商業組合，並輔以一系列行業領先的機會，我們相信禮來公司將繼續成為一項引人注目的投資。

Thanks again for dialing in today. Please follow up with our IR team if you have any questions we have not addressed on today's call. Hope everyone has a great day.

再次感謝您今天撥入。如果您有任何我們在今天的電話會議中沒有解決的問題，請與我們的 IR 團隊聯繫。希望每個人都有美好的一天。

Thank you. Ladies and gentlemen, that does conclude our conference for today. We thank you for your participation and for using AT&T Event Conferencing Service. You may now disconnect.

謝謝你。女士們先生們，今天的會議到此結束。我們感謝您的參與和使用 AT&T 活動會議服務。您現在可以斷開連接。