禮來公司 (LLY) 2022 Q1 法說會逐字稿

Ladies and gentlemen, thank you for standing by, and welcome to the Lilly Q1 2022 Earnings Call. (Operator Instructions) And as a reminder, your conference is being recorded.

女士們，先生們，感謝您的支持，歡迎參加禮來公司 2022 年第一季度財報電話會議。 （操作員說明）作為提醒，您的會議正在錄製中。

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

我現在想將會議轉交給您的主持人 Kevin Hern。請繼續。

Good morning. Thank you for joining us for Eli Lilly and Company's Q1 2022 Earnings Call. I'm Kevin Hern, Vice President of Investor Relations.

早上好。感謝您參加禮來公司 2022 年第一季度財報電話會議。我是投資者關係副總裁 Kevin Hern。

Joining me on today's call are: Dave Ricks, Lilly's Chair and CEO; Anat Ashkenazi, Chief Financial Officer; Dr. Dan Skovronsky, Chief Scientific and Medical Officer; Anne White, President of Lilly Neuroscience; Ilya Yuffa, President of Lilly International; Jake Van Naarden, CEO of Loxo Oncology at Lilly and President of Lilly Oncology; Mike Mason, President of Lilly Diabetes; and Patrik Jonsson, President of Lilly Immunology and Lilly USA. We're also joined by Sara Smith, Kento Ueha and Lauren Zierke of the Investor Relations team.

與我一起參加今天電話會議的有：禮來公司董事長兼首席執行官 Dave Ricks； Anat Ashkenazi，首席財務官； Dan Skovronsky 博士，首席科學和醫學官；禮來公司神經科學總裁 Anne White；禮來國際總裁 Ilya Yuffa； Jake Van Naarden，禮來公司 Loxo 腫瘤學首席執行官兼禮來腫瘤學總裁；禮來糖尿病總裁 Mike Mason；以及禮來免疫學和禮來美國公司總裁 Patrik Jonsson。投資者關係團隊的 Sara Smith、Kento Ueha 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 several factors, including those listed on Slide 3. Additional information concerning factors that could cause actual results to differ materially is contained in our latest Form 10-K and subsequent Forms 10-Q and 8-K filed with the Securities and Exchange Commission.

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，我們的實際結果可能存在重大差異，包括幻燈片 3 中列出的因素。有關可能導致實際結果產生重大差異的因素的其他信息包含在我們最新提交的 10-K 表格和後續 10-Q 和 8-K 表格中與證券交易委員會。

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, please note that our commentary will focus on non-GAAP financial measures.

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，請注意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.

現在我將把電話轉給戴夫。

Thanks, Kevin. 2022 is off to a strong start with solid volume-driven revenue growth led by our key products and the new tirzepatide obesity data we announced this morning. We are focused on driving adoption of our newer medicines, preparing for key product launches, delivering several global submissions for potential new medicines, all the while advancing our pipeline to power the next wave of growth. We are pleased with the progress we saw in the first quarter.

謝謝，凱文。 2022 年開局強勁，我們的主要產品和我們今天早上宣布的新的 tirzepatide 肥胖數據引領了穩定的銷量驅動收入增長。我們專注於推動我們的新藥採用，為關鍵產品的發布做準備，為潛在的新藥提供多個全球提交，同時推進我們的管道以推動下一波增長。我們對第一季度取得的進展感到滿意。

Before I get to our results, I'd like to take a moment to address the tragic loss of life and the hardships we are seeing in Ukraine. Our Ukraine office is currently closed and operations are suspended. The safety of our employees and their families continues to be our top priority. We are working through logistical challenges in order to ensure supply of our medicines to those in need in Ukraine.

在得出我們的結果之前，我想花一點時間來談談我們在烏克蘭看到的悲慘生命損失和困難。我們的烏克蘭辦事處目前關閉，業務暫停。我們的員工及其家人的安全仍然是我們的首要任務。我們正在努力應對後勤挑戰，以確保向烏克蘭有需要的人供應我們的藥品。

Earlier this month, an initial shipment of medicine donated by Lilly, including insulin, arrived in Ukraine, thanks to the tremendous efforts of our partners, Project HOPE and Direct Relief. Few of our clinical trial participants are in Ukraine. So while we're doing everything we can to ensure continuity of their medical care, there is minimal impact to our global trials.

本月早些時候，在我們的合作夥伴 Project HOPE 和 Direct Relief 的巨大努力下，禮來公司捐贈的包括胰島素在內的首批藥物抵達烏克蘭。我們的臨床試驗參與者很少在烏克蘭。因此，雖然我們正在盡一切努力確保他們的醫療服務的連續性，但對我們的全球試驗的影響微乎其微。

With regards to Russia, we have suspended investments, our promotional activities and new clinical trials there. Our Russian operations are now only focused on ensuring people suffering from diseases like cancer and diabetes continue to get the Lilly medicines they need. Should we generate any profits from our sales in Russia, we will donate them to organizations dedicated to humanitarian relief. Our revenue in Russia and Ukraine account for less than 1% of our total company sales in 2021.

關於俄羅斯，我們已暫停在那裡的投資、促銷活動和新的臨床試驗。我們在俄羅斯的業務現在只專注於確保患有癌症和糖尿病等疾病的人繼續獲得他們需要的禮來藥物。如果我們從俄羅斯的銷售中獲得任何利潤，我們將把它們捐贈給致力於人道主義救濟的組織。 2021 年，我們在俄羅斯和烏克蘭的收入不到公司總銷售額的 1%。

Moving to our results, you can see on Slide 4 the progress we've made on our strategic deliverables so far this year. Q1 revenue grew 15% or 17% on a constant currency basis and was driven by volume growth of 20%. When excluding revenue from COVID-19 antibodies and ALIMTA due to loss of exclusivity, revenue grew 10% for the quarter.

轉到我們的結果，您可以在幻燈片 4 上看到我們今年迄今為止在戰略可交付成果方面取得的進展。第一季度收入在固定貨幣基礎上增長了 15% 或 17%，並受到 20% 的銷量增長的推動。由於失去排他性而排除 COVID-19抗體和 ALIMTA 的收入後，本季度收入增長了 10%。

This volume-driven performance in Q1 is attributable to our key growth products, which grew 24% and now account for 61% of our core business. With long IP runways for many of these products and less than 10% of our 2022 revenue exposed to patent expiry in the next 5 years, along with the potential to launch 5 new medicines over the next 18 months, the durability of our growth outlook is quite strong.

第一季度這種以銷量為導向的業績歸功於我們的主要增長產品，該產品增長了 24%，現在占我們核心業務的 61%。由於其中許多產品的知識產權跑道很長，我們 2022 年收入中不到 10% 的收入在未來 5 年內面臨專利到期，而且未來 18 個月有可能推出 5 種新藥，我們的增長前景的持久性是相當強大。

Our non-GAAP gross margin was 76.1% in Q1, an increase of approximately 70 basis points. Excluding revenue from COVID antibodies, gross margin was approximately 80% for the quarter. Our non-GAAP operating margin was 33.4%, an increase of roughly 1,000 basis points, primarily driven by both higher gross margin and lower R&D expenses for COVID antibodies.

我們第一季度的非美國通用會計準則毛利率為 76.1%，增加了約 70 個基點。不包括來自 COVID 抗體的收入，本季度的毛利率約為 80%。我們的非美國通用會計準則營業利潤率為 33.4%，增長了約 1,000 個基點，這主要是由於更高的毛利率和更低的 COVID 抗體研發費用。

In our pipeline, we have several important updates since our Q4 earnings call, including: the U.S. and EU approval for Jardiance in heart failure with preserved ejection fraction as well as a recommendation from the independent data monitoring committee for an early stop to the Phase III trial studying Jardiance for chronic kidney disease due to clear positive efficacy; the U.S. Emergency Use Authorization for bebtelovimab for the treatment of mild-to-moderate COVID-19; the recent U.S. submission of mirikizumab for the treatment of adults with moderately to severely active ulcerative colitis; and a positive Phase III top line readout for SURMOUNT-1, the first of four global studies to evaluate tirzepatide for adults living with obesity or overweight.

在我們的管道中，自第四季度財報電話會議以來，我們有幾項重要更新，包括：美國和歐盟批准 Jardiance 治療射血分數保留的心力衰竭，以及獨立數據監測委員會建議提前停止第三階段由於明確的積極療效，試驗研究 Jardiance 治療慢性腎病； bebtelovimab 用於治療輕度至中度 COVID-19 的美國緊急使用授權；最近美國提交了用於治療患有中度至重度活動性潰瘍性結腸炎的成人的 mirikizumab；以及 SURMOUNT-1 的 III 期陽性讀數，這是評估 tirzepatide 用於肥胖或超重成人的四項全球研究中的第一項。

Dan will talk in more detail later, but we are very excited with the results of the Phase III SURMOUNT-1 top line readout. We believe there is significant potential for tirzepatide to build off the impressive results we saw from our clinical program in type 2 diabetes and help people with obesity, a disease impacting over 110 million people in the United States and approximately 650 million people worldwide. Obesity is a chronic and progressive disease that causes over 2.8 million deaths globally each year.

Dan 稍後會更詳細地討論，但我們對 III 期 SURMOUNT-1 頂線讀數的結果感到非常興奮。我們相信 tirzepatide 具有巨大的潛力，可以在我們從 2 型糖尿病臨床項目中看到的令人印象深刻的結果的基礎上，幫助肥胖症患者，這種疾病影響著美國超過 1.1 億人和全球約 6.5 億人。肥胖是一種慢性進行性疾病，每年在全球造成超過 280 萬人死亡。

The economic impact associated with obesity is more than $1 trillion in the U.S. alone. We believe addressing obesity could make a difference in millions of people's lives, have a significant impact on public health and reduce health care costs. We're hopeful that we are entering a new era of obesity care, where people have medicines that can help treat their obesity. And this is our first proof point on that journey.

僅在美國，與肥胖相關的經濟影響就超過 1 萬億美元。我們相信，解決肥胖問題可以改變數百萬人的生活，對公共衛生產生重大影響並降低醫療保健成本。我們希望我們正在進入一個肥胖護理的新時代，人們擁有可以幫助治療肥胖的藥物。這是我們在這段旅程中的第一個證明點。

We continue to rapidly advance nucleic acid innovation at Lilly, building on our growing portfolio with the launch of the Lilly Institute for Genetic Medicine, a $700 million facility in Boston. We will develop novel RNA and DNA-based medicines as well as push the boundaries of delivery technology to unlock difficult-to-treat targets in key strategic areas for us like neurodegeneration, diabetes and obesity. Finally, we distributed nearly $900 million in dividends in the quarter and completed $1.5 billion in share repurchases.

我們繼續在禮來快速推進核酸創新，以我們不斷增長的產品組合為基礎，在波士頓成立了價值 7 億美元的禮來基因醫學研究所。我們將開發基於 RNA 和 DNA 的新型藥物，並突破遞送技術的界限，在神經退行性疾病、糖尿病和肥胖症等關鍵戰略領域解鎖難以治療的目標。最後，我們在本季度派發了近 9 億美元的股息，並完成了 15 億美元的股票回購。

On Slides 5 and 6, you'll see a list of key events since our Q4 earnings call, including several important regulatory, clinical and COVID-19 antibody updates we are discussing today. Now I'll turn the call over to Anat to review the Q1 results.

在幻燈片 5 和 6 上，您將看到自我們第四季度財報電話會議以來的一系列關鍵事件，包括我們今天討論的幾項重要的監管、臨床和 COVID-19 抗體更新。現在我將把電話轉給 Anat 來查看第一季度的結果。

Thanks, Dave. Before I review the financial results for Q1, it is important to note that beginning this quarter, following direction from the SEC, presentation of non-GAAP measures will now include upfront charges and development milestones related to acquired in-process R&D and development. While this has no bearing on how we conduct our business, it will have an impact on how we represent -- how we present our non-GAAP measures.

謝謝，戴夫。在我回顧第一季度的財務業績之前，重要的是要注意，從本季度開始，按照 SEC 的指示，非 GAAP 措施的介紹現在將包括與獲得的正在進行的研發和開發相關的前期費用和開發里程碑。雖然這與我們開展業務的方式無關，但它將影響我們的代表方式——我們如何展示我們的非公認會計原則措施。

This change in presentation of financial results will have the effect of pulling into non-GAAP measures certain charges that were previously reported only in our GAAP financial results. We expect this change will increase non-GAAP operating expenses and decrease non-GAAP operating margins and earnings per share. To help with the year-on-year comparison of our non-GAAP measures, you can find a revised workbook on our investor website reflecting the updated presentation of our 2020 and 2021 results.

財務結果呈現方式的這種變化將影響非 GAAP 措施的某些費用，這些費用以前僅在我們的 GAAP 財務結果中報告。我們預計這一變化將增加非 GAAP 運營費用並降低非 GAAP 運營利潤率和每股收益。為了幫助對我們的非公認會計原則措施進行同比比較，您可以在我們的投資者網站上找到一份修訂後的工作手冊，其中反映了我們 2020 年和 2021 年業績的更新介紹。

Slide 7 summarizes financial performance in the first quarter of 2022. I'll focus my comments on non-GAAP performance. In Q1, revenue grew 15%. Excluding revenue from COVID-19 antibodies and ALIMTA, revenue increased 10%, highlighting solid momentum for our core business. Gross margin as a percent of revenue increased 70 basis points to 76.1% in Q1 2022.

幻燈片 7 總結了 2022 年第一季度的財務業績。我將把我的評論集中在非 GAAP 業績上。第一季度，收入增長了 15%。不包括 COVID-19 抗體和 Alimta 的收入，收入增長了 10%，突顯了我們核心業務的強勁勢頭。 2022 年第一季度，毛利率佔收入的百分比增加了 70 個基點，達到 76.1%。

The increase in gross margin percent was primarily driven by the unfavorable effect of foreign exchange rates on international inventory sold in Q1 2021, partially offset by increased sales of COVID antibodies, which have lower gross margin profile than the rest of our portfolio and, to a lesser extent, lower realized prices. Increase in manufacturing costs and logistics due to inflation had a modest impact on gross margin in Q1.

毛利率百分比的增加主要是由於外匯匯率對 2021 年第一季度銷售的國際庫存的不利影響，部分被 COVID 抗體的銷售增加所抵消，該抗體的毛利率低於我們的其他產品組合，並且程度越小，實現的價格就越低。通脹導致的製造成本和物流增加對第一季度的毛利率影響不大。

Total operating expenses decreased 6% this quarter, which, as a reminder, is now inclusive of acquired IPR&D and development milestone charges. Marketing, selling and administrative expenses decreased 1% while R&D expenses decreased 4%, driven by lower development expenses for COVID-19 antibodies, partially offset by higher development expenses for late-stage assets.

本季度總運營費用下降了 6%，提醒一下，現在包括收購的 IPR&D 和開發里程碑費用。營銷、銷售和管理費用下降了 1%，而研發費用下降了 4%，這主要是由於 COVID-19 抗體的開發費用降低，部分被後期資產的開發費用增加所抵消。

This quarter, we recognized acquired IPR&D and development milestone charges of $166 million or $0.15 of EPS, primarily related to a purchase of a priority review voucher. In Q1, 2021 acquired IPR&D and development milestone charges were $312 million or $0.27 of EPS.

本季度，我們確認了 1.66 億美元或每股 0.15 美元的收購 IPR&D 和開發里程碑費用，主要與購買優先審查憑證有關。 2021 年第一季度，獲得的 IPR&D 和開發里程碑費用為 3.12 億美元或每股收益 0.27 美元。

Operating income increased 66% in Q1, driven by higher revenue, primarily due to higher sales of COVID antibodies, lower R&D expenses for COVID antibodies and, to a lesser extent, lower acquired IPR&D and development milestone charges. Operating income as a percent of revenue was 33.4% for the quarter and reflects a benefit from COVID-19 antibody revenue as well as the negative impact of approximately 210 basis points attributed to acquired IPR&D and development milestone charges.

第一季度營業收入增長了 66%，這主要是由於 COVID 抗體的銷售額增加、COVID 抗體的研發費用降低，以及在較小程度上獲得的 IPR&D 和開發里程碑費用降低。本季度營業收入佔收入的百分比為 33.4%，反映了 COVID-19抗體收入的收益以及因收購的 IPR&D 和開發里程碑費用而產生的約 210 個基點的負面影響。

Other income and expense was income of approximately $38 million this quarter compared with income of $35 million in Q1 2021. Our Q1 effective tax rate was 10.3%, an increase of 140 basis points compared to the same period in 2021. This increase was driven by a lower net discrete tax benefit this quarter, partially offset by decreased tax expenses related to the implementation of the provision in the 2017 Tax Act requiring to capitalize research and development expenses. At the bottom line, we delivered strong earnings per share growth of 63% in Q1, inclusive of approximately 1,500 basis points related to lower acquired IPR&D and development milestone charges.

其他收入和支出為本季度的收入約為 3800 萬美元，而 2021 年第一季度的收入為 3500 萬美元。我們的第一季度有效稅率為 10.3%，與 2021 年同期相比增加了 140 個基點。這一增長的驅動力是本季度較低的淨離散稅收優惠，部分被與實施 2017 年稅法中要求將研發費用資本化的規定相關的稅收費用減少所抵消。歸根結底，我們在第一季度實現了 63% 的強勁每股收益增長，其中包括與較低的收購 IPR&D 和開發里程碑費用相關的約 1,500 個基點。

On Slide 8, we quantify the effect of price, rate and volume on revenue growth. This quarter, U.S. revenue grew 31%. And when excluding revenue from COVID-19 antibodies and ALIMTA, revenue grew 14% in the U.S. This growth was driven by volume, led by Trulicity, Verzenio, Jardiance, Olumiant and Taltz. We experienced a net price decline of 1% for the quarter and continue to expect a mid-single-digit price decline in the U.S. for the full year. As a reminder, a single competitor to ALIMTA launched in the U.S. in February. And we expect broad generic entry in May, resulting in significant erosion of U.S. ALIMTA revenue.

在幻燈片 8 中，我們量化了價格、費率和數量對收入增長的影響。本季度，美國收入增長了 31%。如果不包括 COVID-19 抗體和 ALIMTA 的收入，美國的收入增長了 14%。這一增長是由 Trulicity、Verzenio、Jardiance、Olumiant 和 Taltz 領導的銷量推動的。我們在本季度經歷了 1% 的淨價格下跌，並繼續預計美國全年價格將出現中個位數的下跌。提醒一下，ALIMTA 的單一競爭對手於 2 月在美國推出。我們預計 5 月份將有廣泛的仿製藥進入，導緻美國 ALIMTA 收入的顯著下降。

Moving to Europe. Revenue in Q1 declined 13% in constant currency. And when excluding revenue from COVID-19 antibodies and ALIMTA, revenue grew 14% in constant currency, driven primarily by volume growth for Trulicity, Taltz, Jardiance, Verzenio and Olumiant. We expect continued growth in Europe, excluding ALIMTA.

搬到歐洲。按固定匯率計算，第一季度的收入下降了 13%。剔除 COVID-19 抗體和 ALIMTA 的收入時，收入增長 14%，主要受 Trulicity、Taltz、Jardiance、Verzenio 和 Olumiant 的銷量增長推動。我們預計歐洲將繼續增長，不包括 ALIMTA。

For Japan, Q1 revenue decreased 21% in constant currency as our business there continues to be negatively affected by significant declines in off-patent products, primarily Cymbalta and ALIMTA. Key growth products now represent 65% of total revenue in Japan. And we expect a return to growth in Japan beginning in 2023.

對於日本，第一季度的收入按固定匯率計算下降了 21%，因為我們的業務繼續受到非專利產品（主要是 Cymbalta 和 Alimta）大幅下降的負面影響。主要增長產品現在佔日本總收入的 65%。我們預計日本將從 2023 年開始恢復增長。

In China, revenue grew 10% in constant currency. The NRDL access has driven significant volume growth for newer products, like Tyvyt, Trulicity, Verzenio and Taltz, and has been partially offset by related price decreases. We expect this improved access to continue to drive future volume growth, more than offsetting the price decline. The recent COVID-19 outbreak in China and the subsequent protective measures that are currently being put in place to control the spread of the virus highlights the potential for commercial impacts in China in the near term, particularly for our infused products like Tyvyt.

在中國，按固定匯率計算，收入增長了 10%。國家醫保目錄的訪問推動了 Tyvyt、Trulicity、Verzenio 和 Taltz 等新產品的顯著銷量增長，並被相關的價格下降部分抵消。我們預計這種改善的准入將繼續推動未來的銷量增長，而不僅僅是抵消價格下跌。最近在中國爆發的 COVID-19 以及目前為控制病毒傳播而採取的後續保護措施凸顯了短期內對中國商業影響的潛力，特別是對我們的輸液產品（如 Tyvyt）。

Revenue in the rest of the world increased 29% in constant currency this quarter, driven primarily by $95 million in revenue from the sales of rights to Cialis in Taiwan and Saudi Arabia as well as by increased sales of key growth products.

本季度全球其他地區的收入按固定匯率計算增長了 29%，這主要是由於在台灣和沙特阿拉伯向 Cialis 出售版權所帶來的 9500 萬美元收入以及關鍵增長產品的銷售增加。

We continue to expect a mid-single-digit net price decline in 2022 for the U.S., Europe and Japan with a worldwide net price decline in the high single digits, driven by the expanded NRDL access for our products in China.

我們繼續預計 2022 年美國、歐洲和日本的淨價格將出現中個位數的下降，而全球淨價格的下降幅度將達到高個位數，這是由於我們產品在中國擴大了 NRDL 准入範圍。

As shown on Slide 9, our key growth products continued to drive robust worldwide volume growth. These products drove nearly 15 percent points of volume growth this quarter and continued to bolster overall performance and outlook.

如幻燈片 9 所示，我們的主要增長產品繼續推動全球銷量強勁增長。這些產品在本季度推動了近 15% 的銷量增長，並繼續提升整體業績和前景。

Slide 10 further highlights contributions of our key growth products. This quarter, these brands generated $3.9 billion in revenue and made up 61% of our core business revenue, growing 24%. We're pleased with the continued market growth of both the GLP-1 and SGLT2 classes, where Trulicity and Jardiance are market leaders, as well as with the strong Taltz prescription growth. We're also encouraged by the significant uptake of Verzenio in Q1, driven by the approval and launch of the adjuvant indication, which has led to an inflection in both new and total prescriptions.

幻燈片 10 進一步突出了我們主要增長產品的貢獻。本季度，這些品牌創造了 39 億美元的收入，占我們核心業務收入的 61%，增長 24%。我們對 GLP-1 和 SGLT2 類別的持續市場增長感到高興，其中 Trulicity 和 Jardiance 是市場領導者，以及強勁的 Taltz 處方增長。我們還對第一季度 Verzenio 的大量使用感到鼓舞，這得益於輔助適應症的批准和推出，這導致了新處方和總處方的變化。

On Slide 11, we provide an update on capital allocation. In Q1 2022, we invested $2.4 billion to drive our future growth through a combination of R&D expenditures, business development outlays and capital investments. In addition, we returned approximately $900 million to shareholders in dividends and repurchased $1.5 billion in stock. Our capital allocation priorities remain unchanged as we continue to fund our key marketed products and expected new launches, invest in our pipeline, pursue opportunities for external innovation to augment our future growth prospects and return excess capital to shareholders.

在幻燈片 11 中，我們提供了資本配置的最新信息。 2022 年第一季度，我們投資了 24 億美元，通過結合研發支出、業務發展支出和資本投資來推動我們的未來增長。此外，我們向股東返還了大約 9 億美元的股息，並回購了 15 億美元的股票。我們的資本配置優先事項保持不變，因為我們繼續為我們的主要上市產品和預期的新產品提供資金，投資我們的管道，尋求外部創新機會以擴大我們未來的增長前景並將多餘的資本返還給股東。

Slide 12 is our updated 2022 financial guidance. As I previously noted, our presentation of non-GAAP financial measures will now include IPR&D and development milestone charges. For guidance, we will include charges that have been incurred or realized as of the date of the earnings release and will not include any impact from potential or pending business development.

幻燈片 12 是我們更新的 2022 年財務指南。正如我之前提到的，我們對非 GAAP 財務指標的介紹現在將包括 IPR&D 和開發里程碑費用。作為指導，我們將包括截至收益發布之日已發生或已實現的費用，不包括潛在或未決業務發展的任何影響。

We're providing information that should make this change as easy as possible to understand as well as incorporate into modeling. As always, please let us know if there's anything else we can do to be of assistance as you navigate through this transition. I do want to reiterate that margin expansion continues to be a priority for our team. Consistent with prior communication, excluding IPR&D and development milestone charges, we expect to drive further non-GAAP operating margin expansion over time.

我們提供的信息應該使這種變化盡可能容易理解並融入到建模中。與往常一樣，請讓我們知道在您完成此過渡時，我們還能做些什麼來為您提供幫助。我確實想重申，利潤率擴張仍然是我們團隊的首要任務。與之前的溝通一致，不包括 IPR&D 和開發里程碑費用，我們預計隨著時間的推移將進一步推動非 GAAP 營業利潤率的擴大。

Getting into the numbers underlying our updated guidance. There are several items that benefited first quarter results which are not expected to recur. These include: approximately $1.45 billion of COVID antibody sales; U.S. ALIMTA revenue of approximately $250 million that will be impacted by multi-sourced generic entrants in Q2 and beyond; a favorable effective tax rate; and a one-time benefit related to the resolution of cefaclor patent litigation in Canada. I would also remind you that as we look ahead to the second quarter that Q2 2021 revenue benefited from the sale of Cialis rights in China, which will provide roughly 2.5 percentage points of headwind to our top line growth in Q2.

了解我們更新指南背後的數字。有幾個項目受益於第一季度的結果，預計不會再次出現。其中包括：大約 14.5 億美元的 COVID 抗體銷售額；美國 ALIMTA 收入約為 2.5 億美元，將受到第二季度及以後多源仿製藥進入者的影響；優惠的有效稅率；以及與解決加拿大頭孢克洛專利訴訟有關的一次性福利。我還要提醒您，當我們展望第二季度時，2021 年第二季度的收入受益於出售 Cialis 在中國的權利，這將為我們第二季度的收入增長帶來大約 2.5 個百分點的阻力。

Starting with revenue, we are increasing the guidance range by $1 billion to now be in the range of $28.8 billion to $29.3 billion, reflecting the additional revenue from bebtelovimab sales in Q1. While we project an unfavorable impact from foreign exchange rate, we are expecting to offset it with stronger core business performance. We anticipate that any additional revenue from sales of COVID-19 antibodies to be limited beginning Q2 2022. While the U.S. government has an option to purchase additional 500,000 doses of bebtelovimab no later than July 31 of this year, it is uncertain whether this option will be exercised. And therefore, it is not included in our guidance.

從收入開始，我們將指導範圍增加 10 億美元，目前在 288 億美元至 293 億美元之間，這反映了第一季度貝貝特洛維單抗銷售的額外收入。雖然我們預計匯率會產生不利影響，但我們預計會通過更強勁的核心業務表現來抵消它。我們預計，從 2022 年第二季度開始，銷售 COVID-19 抗體的任何額外收入都將受到限制。雖然美國政府可以選擇不遲於今年 7 月 31 日購買額外的 500,000 劑 bebtelovimab，但不確定該選擇是否會被行使。因此，它不包含在我們的指導中。

Moving down the income statement. GAAP gross margin percent is now expected to be approximately 76% while non-GAAP gross margin is now expected to be approximately 78%. The majority of this 200 basis point reduction is due to the impact of Q1 bebtelovimab sales, which has lower gross margin and, to a lesser extent, an increase of approximately $100 million in logistics and manufacturing costs due to inflation. The range for R&D expenses has been increased by $100 million to be $7.1 billion to $7.3 billion, driven by investment in our late-stage pipeline, primarily Alzheimer's clinical development, and investment to advance the diagnostics ecosystem.

向下移動損益表。 GAAP 毛利率現在預計約為 76%，而非 GAAP 毛利率現在預計約為 78%。這 200 個基點的減少大部分是由於第一季度 bebtelovimab 銷售的影響，其毛利率較低，並且在較小程度上，由於通貨膨脹導致物流和製造成本增加了約 1 億美元。研發費用的範圍增加了 1 億美元，達到 71 億美元至 73 億美元，這得益於對我們後期管道的投資，主要是阿爾茨海默氏症的臨床開發，以及對推進診斷生態系統的投資。

Our guidance includes acquired IPR&D and development milestone charges of approximately $521 million, reflecting Q1 charges of $166 million, with the remainder primarily related to a charge associated with the buyout of future obligations that were contingent upon development, regulatory and commercial success of our mutant selective [PI3Ka] (corrected by the company after the call) inhibitor. This guidance does not include any impact from potential or pending business development transactions.

我們的指導包括約 5.21 億美元的收購 IPR&D 和開發里程碑費用，反映了 1.66 億美元的第一季度費用，其餘主要與收購未來義務相關的費用，這取決於我們的突變選擇性的開發、監管和商業成功[PI3Ka]（由公司調用後更正）抑製劑。本指南不包括潛在或未決業務發展交易的任何影響。

GAAP and non-GAAP operating margin decreased 200 basis points to approximately 28% and 30%, respectively, primarily due to the negative impact associated with the acquired IPR&D and development milestone charges to date. Given the accounting change for acquired IPR&D and development milestone charges and the inherent variability associated with such charges, our non-GAAP operating margin figure will not measure efficiency in the same way it has done historically. However, you can track our operating margin in the way you deem most appropriate, knowing that we aim to expand operating margin over time, excluding acquired IPR&D and development milestone charges.

GAAP 和非 GAAP 營業利潤率分別下降 200 個基點至約 28% 和 30%，主要是由於與迄今為止收購的 IPR&D 和開發里程碑費用相關的負面影響。鑑於收購的 IPR&D 和開發里程碑費用的會計變化以及與此類費用相關的固有可變性，我們的非公認會計原則營業利潤率數據將不會以與以往相同的方式衡量效率。但是，您可以以您認為最合適的方式跟踪我們的營業利潤率，因為我們的目標是隨著時間的推移擴大營業利潤率，不包括獲得的 IPR&D 和開發里程碑費用。

Our Q1 2022 tax rate and EPS include a favorable impact from the provision in the 2017 Tax Act that requires capitalization of research and development expenses for tax purposes. Our financial guidance for the full year is unchanged and assumed that this provision will be deferred or repealed by Congress, effective for 2022. If this provision is not deferred or repealed effective this year, then we would expect our reported and non-GAAP tax rates to be approximately 10% to 11%. It is notable that while this provision favorably impacts certain tax items, which decrease our effective tax rate, we expect it will increase our 2022 cash payments of income taxes by approximately $1.5 billion.

我們 2022 年第一季度的稅率和每股收益包括 2017 年稅法中要求將研發費用資本化以用於稅收目的的規定的有利影響。我們對全年的財務指導保持不變，並假設國會將推遲或廢除這一規定，自 2022 年起生效。如果今年不推遲或廢除這一規定，那麼我們預計我們的報告稅率和非公認會計準則稅率約為 10% 至 11%。值得注意的是，雖然這項規定對某些稅收項目產生了有利影響，從而降低了我們的有效稅率，但我們預計它將使我們 2022 年的所得稅現金支付增加約 15 億美元。

Based on these changes, we have lowered our reported EPS guidance by $0.70 to now be in the range of $7.30 to $7.45 per share and lowered our non-GAAP EPS guidance to be in the range of $8.15 to $8.30. That $0.35 reduction in our non-core -- in our non-GAAP EPS range includes a $0.55 decrease due to the year-to-date acquired IPR&D and development milestone charges, partially offset by improved business performance of $0.20 attributable to the net benefit of Q1 bebtelovimab sales and increased investments in R&D.

基於這些變化，我們將報告的每股收益指引下調了 0.70 美元，目前在每股 7.30 美元至 7.45 美元的範圍內，並將我們的非公認會計準則每股收益指引下調至 8.15 美元至 8.30 美元的範圍內。我們的非核心 - 在我們的非 GAAP 每股收益範圍內減少 0.35 美元，其中包括由於年初至今收購的 IPR&D 和開發里程碑費用而減少的 0.55 美元，部分被歸因於淨收益的 0.20 美元的業務績效改善所抵消第一季度 bebtelovimab 銷售額和研發投資增加。

Now I'll 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. Let me start with today's exciting announcement, the positive top line results from the tirzepatide SURMOUNT-1 Phase III study.

謝謝，阿納特。讓我從今天令人興奮的公告開始，即 tirzepatide SURMOUNT-1 III 期研究的積極頂線結果。

Participants without type 2 diabetes who have obesity or overweight with at least 1 comorbidity achieved up to 22.5% weight loss at 72 weeks, which translates to a mean weight loss of 52 pounds. Tirzepatide is the first investigational medicine to deliver more than 20% weight loss on average in a Phase III study. Indeed, most people on 10 or 15 milligrams of tirzepatide in this trial achieved 20% or greater weight loss and up to 63% of patients on 15 milligrams achieved this level of weight reduction.

患有肥胖或超重且至少有 1 種合併症的非 2 型糖尿病參與者在 72 週時體重減輕高達 22.5%，這意味著平均體重減輕 52 磅。 Tirzepatide 是第一個在 III 期研究中平均減輕體重超過 20% 的研究藥物。事實上，在這項試驗中，大多數服用 10 或 15 毫克 tirzepatide 的人實現了 20% 或更多的體重減輕，高達 63% 的服用 15 毫克的患者達到了這種減肥水平。

Obesity is a chronic disease that needs more effective treatment options for patients. We're working hard at Lilly to create new potentially innovative medicines with the aim to modernize how this disease is approached. We hope that tirzepatide can be Lilly's first such medicine. And the SURMOUNT program has been designed to test just that. I'll cover this SURMOUNT-1 results in more detail. But first, let me quickly provide an overview of the SURMOUNT Phase III program.

肥胖是一種慢性疾病，需要為患者提供更有效的治療方案。我們正在禮來（Lilly）努力開發新的潛在創新藥物，旨在使治療這種疾病的方式現代化。我們希望 tirzepatide 可以成為禮來公司的第一個此類藥物。 SURMOUNT 計劃就是為了測試這一點而設計的。我將更詳細地介紹這個 SURMOUNT-1 結果。但首先，讓我快速概述一下 SURMOUNT 第三階段計劃。

The SURMOUNT program has enrolled more than 5,000 people with obesity or overweight across 6 studies, 4 of which are global registration studies. On Slide 13, you can see key trial design elements for those 4 global registration studies. All 4 studies compare the efficacy and safety of tirzepatide to placebo as an adjunct to reduced calorie diet and increased physical activity.

SURMOUNT 計劃在 6 項研究中招募了 5,000 多名肥胖或超重患者，其中 4 項是全球註冊研究。在幻燈片 13 上，您可以看到這 4 項全球註冊研究的關鍵試驗設計元素。所有 4 項研究都比較了替西帕肽與安慰劑作為減少卡路里飲食和增加體力活動的輔助手段的療效和安全性。

SURMOUNT-1 was designed to evaluate treatment with tirzepatide compared to placebo to provide weight reduction and safety data for people without type 2 diabetes with obesity or overweight with at least 1 comorbidity. SURMOUNT-2 will provide weight reduction and safety data for people with obesity or overweight with type 2 diabetes. SURMOUNT-3 will provide data on maximizing weight loss following an intensive lifestyle program. And SURMOUNT-4 evaluates maintaining weight loss. We expect the remaining 3 global studies to read out in the middle of 2023.

SURMOUNT-1 旨在評估與安慰劑相比使用 tirzepatide 的治療，以便為患有肥胖或超重且至少有 1 種合併症的非 2 型糖尿病患者提供體重減輕和安全性數據。 SURMOUNT-2 將為肥胖或超重的 2 型糖尿病患者提供減肥和安全數據。 SURMOUNT-3 將提供在強化生活方式計劃後最大限度地減輕體重的數據。 SURMOUNT-4 評估維持體重減輕。我們預計剩餘的 3 項全球研究將在 2023 年年中公佈。

Note that dose escalation in the SURMOUNT program is consistent with that of the SURPASS program for the treatment of type 2 diabetes with tirzepatide. Patients start with 2.5 milligrams of tirzepatide and move up every 4 weeks in 2.5-milligram increments to reach their target dose. In SURMOUNT-3 and 4, study participants will escalate to the maximum tolerated dose of either 10 milligrams or 15 milligrams. Patients escalating to the maximum tolerated dose provides the opportunity to evaluate the full potential for weight reduction.

請注意，SURMOUNT 計劃中的劑量遞增與替西帕肽治療 2 型糖尿病的 SURPASS 計劃一致。患者從 2.5 毫克的替西帕肽開始，每 4 週以 2.5 毫克的增量增加，以達到他們的目標劑量。在 SURMOUNT-3 和 4 中，研究參與者將升級到 10 毫克或 15 毫克的最大耐受劑量。患者升級到最大耐受劑量提供了評估減輕體重的全部潛力的機會。

Studies vary in duration from 72 to 88 weeks. And SURMOUNT-1 will continue through 176 weeks to evaluate whether tirzepatide can actually slow the time to onset of type 2 diabetes in participants who had prediabetes at the time of entering the clinical trial. We believe this will be important additional information for patients and physicians.

研究的持續時間從 72 周到 88 週不等。 SURMOUNT-1 將持續 176 週，以評估 tirzepatide 是否真的可以減緩在進入臨床試驗時患有前驅糖尿病的參與者的 2 型糖尿病發病時間。我們相信這對患者和醫生來說將是重要的附加信息。

SURMOUNT-1, a large trial, which enrolled over 2,500 participants met its co-primary study endpoints and also hit on all prespecified key secondary end points. On Slide 14, you can see the first co-primary endpoint in the SURMOUNT-1 study, where tirzepatide delivered up to 22.5% mean body weight reduction in adults with obesity or overweight. With a mean baseline weight across the study of 231 pounds, this translates into a mean body weight reduction of 52 pounds on the 15-milligram treatment arm of the study. Along with the impressive results from the 10-milligram dose, which showed 21.4% mean body weight reduction, we were also very pleased to see how well the 5-milligram arm performed with a 16% mean body weight reduction, also at 72 weeks for the efficacy estimand.

SURMOUNT-1 是一項大型試驗，招募了 2,500 多名參與者，達到了其共同主要研究終點，並達到了所有預先指定的關鍵次要終點。在幻燈片 14 上，您可以看到 SURMOUNT-1 研究中的第一個共同主要終點，其中 tirzepatide 可使肥胖或超重的成年人平均體重減輕高達 22.5%。整個研究的平均基線體重為 231 磅，這意味著該研究的 15 毫克治療組的平均體重減少了 52 磅。除了 10 毫克劑量的令人印象深刻的結果（顯示平均體重減輕 21.4%）外，我們還很高興地看到 5 毫克劑量的平均體重減輕 16%，同樣在 72 週時表現如何療效估計。

Moving to Slide 15. Tirzepatide obviously achieved the second co-primary endpoint of driving at least 5% weight reduction. Clearly, the vast majority of subjects, including greater than 96% of participants in the 10- and 15-milligram arms, achieved this level of weight reduction. We're really excited that a key secondary endpoint in SURMOUNT-1 showed up to 63% of patients achieved at least 20% body weight reduction at 72 weeks, again using the efficacy estimand. This is compared to only 1% of participants who achieved greater than 20% weight loss on placebo as an adjunct to diet and exercise.

轉到幻燈片 15。 Tirzepatide 顯然實現了第二個共同主要終點，即減重至少 5%。顯然，絕大多數受試者，包括超過 96% 的 10 和 15 毫克組的參與者，都達到了這種減輕體重的水平。我們真的很高興 SURMOUNT-1 中的一個關鍵次要終點顯示多達 63% 的患者在 72 週時實現了至少 20% 的體重減輕，再次使用療效估計值。相比之下，只有 1% 的參與者使用安慰劑作為飲食和運動的輔助手段，體重減輕超過 20%。

Moving to Slide 16. You could see the safety profile from the SURMOUNT-1 study. Tirzepatide was well tolerated in study participants with the overall safety and tolerability profile similar to incretin-based therapies approved for the treatment of obesity. As in the SURPASS program, the most common reported adverse events were GI-related, generally mild to moderate in severity and usually occurred during dose escalation. Treatment discontinuation rates due to adverse events were between 4.3% and 7.1% for tirzepatide treatment arms compared to 2.6% for placebo. The overall treatment discontinuation rates range from roughly 14% to 16% in the tirzepatide arms compared to over 26% for placebo.

轉到幻燈片 16。您可以從 SURMOUNT-1 研究中看到安全概況。 Tirzepatide 在研究參與者中具有良好的耐受性，其總體安全性和耐受性與批准用於治療肥胖的基於腸促胰島素的療法相似。與 SURPASS 計劃一樣，報告的最常見不良事件與 GI 相關，嚴重程度通常為輕度至中度，通常發生在劑量增加期間。替西帕肽治療組因不良事件導致的治療中斷率為 4.3% 至 7.1%，而安慰劑組為 2.6%。 tirzepatide 組的總體治療停藥率約為 14% 至 16%，而安慰劑組則超過 26%。

The minimal weight loss seen in the placebo treatment group, combined with the observed placebo discontinuation rate of 26%, demonstrates the limited efficacy of diet and exercise alone and highlights the significant unmet medical need for people with this disease. We'll continue to evaluate the SURMOUNT-1 study data and are planning to present findings at a medical meeting in the second half of this year. And of course, we plan to submit our manuscript to a top-tier peer-reviewed journal.

在安慰劑治療組中看到的最小體重減輕，加上觀察到的 26% 的安慰劑停藥率，證明了單獨飲食和運動的有限功效，並突出了患有這種疾病的人的重大未滿足的醫療需求。我們將繼續評估 SURMOUNT-1 研究數據，併計劃在今年下半年的醫學會議上展示研究結果。當然，我們計劃將我們的手稿提交給頂級同行評審期刊。

As Dave mentioned earlier, obesity is a chronic disease impacting over 110 million Americans. And there is great need for more effective treatment options. While our current alignment with the FDA is to complete the 4 SURMOUNT global registrational studies prior to submission, we believe the impressive results from SURMOUNT-1 warrant further discussion. Based on our existing robust data set, we're looking forward to reviewing the data with the FDA and discussing the potential for an expedited path forward for this indication.

正如戴夫之前提到的，肥胖是一種影響超過 1.1 億美國人的慢性疾病。並且非常需要更有效的治療方案。雖然我們目前與 FDA 的合作是在提交之前完成 4 項 SURMOUNT 全球註冊研究，但我們相信 SURMOUNT-1的令人印象深刻的結果值得進一步討論。基於我們現有的強大數據集，我們期待與 FDA 審查數據並討論加快該適應症前進道路的可能性。

Moving to the rest of the portfolio. Slide 17 shows select pipeline opportunities as of April 27 and Slide 18 shows potential key events for the year. There have been several other important developments since our last earnings call. And I'll cover these by therapeutic area.

轉移到投資組合的其餘部分。幻燈片 17 顯示了截至 4 月 27 日的選定管道機會，幻燈片 18 顯示了今年潛在的關鍵事件。自上次財報電話會議以來，還有其他幾項重要進展。我將按治療領域介紹這些內容。

In diabetes, along with our partner, Boehringer Ingelheim, we're proud of the expanded indication for Jardiance as a treatment for heart failure with preserved ejection fraction, which has been classified as the single largest unmet need in cardiovascular medicine. Jardiance is now the first and only heart failure therapy to demonstrate a statistically significant risk reduction in cardiovascular death or hospitalization for heart failure, regardless of ejection fraction.

在糖尿病方面，我們與我們的合作夥伴勃林格殷格翰（Boehringer Ingelheim）一起為 Jardiance 擴大適應症而感到自豪，該適應症是一種治療射血分數保留的心力衰竭，這已被歸類為心血管醫學中最大的未滿足需求。 Jardiance 現在是第一個也是唯一一個證明心血管死亡或心力衰竭住院風險在統計學上顯著降低的心力衰竭療法，無論射血分數如何。

We also announced the Phase III trial study in Jardiance for chronic kidney disease will stop early due to clear positive efficacy. The recommendation was made by an independent data monitoring committee. And while we've not yet seen results from this interim analysis, we're excited about the potential for this new indication and expect to share detailed results from the upcoming primary analysis at a medical meeting in the second half of this year.

我們還宣布，由於明確的積極療效，Jardiance 的慢性腎病 III 期試驗研究將提前停止。該建議是由一個獨立的數據監測委員會提出的。雖然我們尚未看到這項中期分析的結果，但我們對這一新適應症的潛力感到興奮，並希望在今年下半年的一次醫學會議上分享即將進行的初步分析的詳細結果。

Last month, we began dosing patients in the first of five Phase III trials for investigational weekly insulin basal insulin Fc, or BIF. The QWINT-3 trial compares weekly BIF to insulin degludec, where patients are currently treated with basal insulin. We intend to start the other four Phase III trials later this year. You'll also see we've advanced our long-acting amylin receptor agonist to Phase I development in obesity.

上個月，我們開始在五個 III 期試驗中的第一個中為患者給藥，以進行每週胰島素基礎胰島素 Fc 或 BIF 的研究。 QWINT-3 試驗將每週 BIF 與胰島素 degludec 進行比較，患者目前接受基礎胰島素治療。我們打算在今年晚些時候開始其他四項 III 期試驗。您還將看到我們已經將我們的長效胰淀素受體激動劑推進到肥胖症的 I 期開發。

Shifting to immunology. We presented mirikizumab induction data from LUCENT-1 at the European Crohn's and Colitis Virtual Congress, demonstrating superiority over placebo for the primary and all key secondary endpoints. These data show patients with moderately to severely active ulcerative colitis achieved statistically superior rates of clinical remission compared to patients taking placebo with nearly 2/3 of patients responding to mirikizumab. The results indicated improved symptom relief, including decreased bowel urgency and resolution or near resolution of inflammation.

轉向免疫學。我們在歐洲克羅恩病和結腸炎虛擬大會上展示了來自 LUCENT-1 的 mirikizumab 誘導數據，證明在主要和所有關鍵次要終點方面優於安慰劑。這些數據顯示，與服用安慰劑的患者相比，中度至重度活動性潰瘍性結腸炎患者的臨床緩解率在統計學上更高，近 2/3 的患者對 mirikizumab 有反應。結果表明症狀緩解得到改善，包括腸道緊迫感降低和炎症消退或接近消退。

Building upon the positive outcomes from LUCENT-1, we look forward to sharing maintenance data from LUCENT-2 later in Q2. We're also excited to announce that we've submitted to the FDA and expect submissions in Europe and Japan in Q2. Mirikizumab has the potential to be the first-in-class IL-23p19 inhibitor treatment for people with ulcerative colitis.

基於 LUCENT-1 的積極成果，我們期待在第二季度晚些時候分享 LUCENT-2 的維護數據。我們也很高興地宣布，我們已經向 FDA 提交了申請，預計第二季度將在歐洲和日本提交。 Mirikizumab 有可能成為治療潰瘍性結腸炎患者的一流 IL-23p19 抑製劑治療藥物。

Last month, at the American Academy of Dermatology Annual Meeting, we shared lebrikizumab monotherapy data, showing more than 50% of patients with moderate-to-severe atopic dermatitis experienced at least 75% reduction in disease severity at 16 weeks. Additionally, at the Revolutionizing Atopic Dermatitis Conference, we shared data showing 70% of patients receiving lebrikizumab combined with topical corticosteroids achieved at least 75% improvement in overall disease severity.

上個月，在美國皮膚病學會年會上，我們分享了 lebrikizumab 單藥治療數據，顯示超過 50% 的中度至重度特應性皮炎患者在 16 週時疾病嚴重程度至少降低了 75%。此外，在革命性特應性皮炎會議上，我們分享的數據顯示，接受 lebrikizumab 聯合局部皮質類固醇治療的患者中有 70% 的整體疾病嚴重程度至少改善了 75%。

We believe these data could help establish a competitive profile for lebrikizumab. And we're looking forward to further data from our maintenance studies in the first half of this year to provide insight into the durability of efficacy. Global submissions are expected by year-end.

我們相信這些數據可以幫助建立 lebrikizumab 的競爭概況。我們期待在今年上半年從我們的維護研究中獲得更多數據，以深入了解功效的持久性。全球提交預計在年底前完成。

Moving to baricitinib. The FDA review for alopecia areata is underway. And we're pleased to note that the FDA has granted priority review designation. As expected, we also received a Complete Response Letter from the FDA for baricitinib atopic dermatitis indication as we were not in alignment with the agency on the indicated population.

轉向巴瑞替尼。 FDA 對斑禿的審查正在進行中。我們很高興地註意到 FDA 已授予優先審查指定。正如預期的那樣，我們還收到了 FDA 關於巴瑞克替尼特應性皮炎適應症的完整回复信，因為我們在指定人群上與 FDA 不一致。

Finally, in immunology, we have discontinued the Phase II study for IL-2 in ulcerative colitis due to a lack of efficacy based on interim analysis. The safety was consistent with that observed in previous studies. And this decision does not impact the ongoing or planned studies for IL-2 in SLE or atopic dermatitis as each disease state evaluates a different clinical hypothesis.

最後，在免疫學方面，由於缺乏基於中期分析的療效，我們已經停止了 IL-2 在潰瘍性結腸炎中的 II 期研究。安全性與先前研究中觀察到的一致。並且這一決定不會影響正在進行或計劃進行的 SLE 或特應性皮炎中 IL-2 的研究，因為每種疾病狀態都會評估不同的臨床假設。

Moving on to neuroscience and the national coverage determination issued earlier this month for monoclonal antibodies directed against amyloid. We share the disappointment of patients and their caregivers with this NCD. And we know, more generally, that innovation in new medical areas nearly always starts with data that are less proven and more debated and may proceed initially through regulatory mechanisms such as accelerated approval. We believe that Medicare's decision to use CED in such circumstances is in conflict with FDA's and Congress' intent of expedited regulatory pathways and is likely to have a stifling effect on innovation for new medical areas, causing harm to patients that are waiting and in need of new medicines.

繼續討論神經科學和本月早些時候發布的針對澱粉樣蛋白的單克隆抗體的全國覆蓋率確定。我們與這種 NCD 分享患者及其護理人員的失望。而且我們更普遍地知道，新醫療領域的創新幾乎總是從未經證實和爭論更多的數據開始，並且最初可能通過加速批准等監管機制進行。我們認為，Medicare 在這種情況下使用 CED 的決定與 FDA 和國會加快監管途徑的意圖相衝突，並可能對新醫療領域的創新產生抑製作用，對等待和需要的患者造成傷害新藥。

That said, we're continuing with our rolling submission to the FDA under the accelerated approval pathway. We intend to complete our initial submission yet in Q2, enabling a potential regulatory decision in early 2023. We believe it would be beneficial for donanemab to obtain accelerated approval proximal to the TRAILBLAZER-ALZ 2 Phase III readout in mid-2023, which would enable parallel discussions with CMS regarding outright coverage and expedited review time for full FDA approval.

也就是說，我們將繼續在加速批准途徑下向 FDA 滾動提交。我們打算在第二季度完成我們的初始提交，從而在 2023 年初做出潛在的監管決定。我們認為，多納奈馬在 2023 年中期獲得接近 TRAILBLAZER-ALZ 2 III 期讀數的加速批准將是有益的，這將使與 CMS 就直接覆蓋範圍和加快 FDA 完全批准的審查時間進行平行討論。

We believe that given the thoughtful and robust design of TRAILBLAZER-ALZ 2, if the study is positive, it should meet the high level of evidence criteria set forth by CMS in the NCD decision. At that time, we will advocate for CMS to reconsider outright coverage of donanemab. As we stated previously, it's inconceivable to us that once substantial evidence of clinical benefit has been established for any Alzheimer's medicine, people with the disease won't have access to it. Our view of the mid- and long-term opportunity to help patients with donanemab remains unchanged.

我們認為，鑑於 TRAILBLAZER-ALZ 2 的周到和穩健的設計，如果該研究是積極的，它應該符合 CMS 在 NCD 決定中規定的高水平證據標準。屆時，我們將倡導 CMS 重新考慮對 donanemab 的直接報導。正如我們之前所說，我們無法想像，一旦為任何阿爾茨海默病藥物確定了臨床益處的實質性證據，患有該疾病的人將無法獲得它。我們對幫助多那單抗患者的中長期機會的看法保持不變。

Shifting now to oncology with pirtobrutinib. We are also working on a rolling submission here under the accelerated approval pathway, in this case, for mantle cell lymphoma. Here, we also expect to complete our initial submission in Q2. We received a Complete Response Letter from the FDA regarding the submission for sintilimab, which was in line with our expectation after the Oncologic Drugs Advisory Committee meeting earlier this year. Along with Innovent, we're assessing next steps for sintilimab in the U.S.

現在轉向使用 pirtobrutinib 的腫瘤學。我們還在加速批准途徑下在這裡滾動提交，在這種情況下，用於套細胞淋巴瘤。在這裡，我們還希望在第二季度完成我們的初始提交。我們收到了 FDA 關於提交信迪利單抗的完整回复信，這符合我們在今年早些時候腫瘤藥物諮詢委員會會議後的預期。與 Innovent 一起，我們正在評估 sintilimab 在美國的後續步驟。

Further, in the oncology pipeline, we started two additional Phase III studies. The first is an additional study evaluating Verzenio in HR-positive, HER2-negative advanced or metastatic breast cancer in combination with fulvestrant following progression on a CDK4/6 inhibitor and endocrine therapy. The second is CYCLONE 3 evaluating Verzenio in earlier lines of prostate cancer.

此外，在腫瘤學管道中，我們開始了兩項額外的 III 期研究。第一項是另一項研究，評估 Verzenio 在 HR 陽性、HER2 陰性晚期或轉移性乳腺癌中與氟維司群聯合治療 CDK4/6 抑製劑和內分泌治療進展後的療效。第二個是 CYCLONE 3 在早期前列腺癌中評估 Verzenio。

We've also advanced our next-generation RET inhibitor to Phase I development. And we've discontinued our Aura A Kinase inhibitor as we did not see sufficient monotherapy activity to warrant further development. Similarly, in our pain therapeutic area, we have decided to discontinue development of epiregulin / TGF-alpha because it did not meet criteria for proceeding.

我們還將我們的下一代 RET 抑製劑推進到 I 期開發。我們已經停止了我們的 Aura A 激酶抑製劑，因為我們沒有看到足夠的單一療法活性來保證進一步的開發。同樣，在我們的疼痛治療領域，我們決定停止開發上皮調節蛋白/TGF-α，因為它不符合繼續進行的標準。

Finally, as Dave mentioned earlier, the FDA authorized bebtelovimab for emergency use for certain nonhospitalized patients with mild-to-moderate COVID-19. Bebtelovimab neutralizes Omicron, including the BA.2 sublineage as demonstrated by pseudovirus and authentic virus neutralization assays.

最後，正如 Dave 之前提到的，FDA 授權 bebtelovimab 用於某些非住院輕至中度 COVID-19 患者的緊急使用。 Bebtelovimab 中和 Omicron，包括 BA.2 亞系，如假病毒和真實病毒中和試驗所示。

As you can see, Q1 was another busy but successful quarter for pipeline advancement at Lilly. Now I'll turn the call back to Dave for some closing remarks.

如您所見，第一季度是禮來公司管道推進的又一個繁忙但成功的季度。現在，我將把電話轉回戴夫，以發表一些結束語。

Thanks, Dan. Before we go to Q&A, let me briefly sum up the progress we've made this year.

謝謝，丹。在進行問答之前，讓我簡單總結一下我們今年取得的進展。

We delivered solid sales growth, driven largely by volume from our key growth products, which represents 61% of our core business. We continue to see opportunity for meaningful operating margin expansion over time, excluding the impact of acquired IPR&D and development milestone charges. We made significant progress developing new medicines with exciting advances, including for Jardiance in HFpEF, the EUA authorization for bebtelovimab, the submission of mirikizumab in ulcerative colitis as well as positive base results for tirzepatide in obesity and Jardiance in chronic kidney disease. Finally, we returned $2.4 billion to shareholders via the dividend and share repurchase.

我們實現了穩健的銷售增長，這主要得益於我們主要增長產品的銷量，占我們核心業務的 61%。我們繼續看到隨著時間的推移有意義的營業利潤率擴張的機會，不包括收購的知識產權和開發里程碑費用的影響。我們在開發具有令人興奮的進展的新藥方面取得了重大進展，包括用於 HFpEF 的 Jardiance、bebtelovimab 的 EUA 授權、提交用於潰瘍性結腸炎的 mirikizumab 以及用於肥胖症的 tirzepatide 和用於慢性腎病的 Jardiance 的陽性基礎結果。最後，我們通過股息和股票回購向股東返還了 24 億美元。

We are committed to invest for the long term to advance promising R&D opportunities and support launches to bring groundbreaking therapies to patients diagnosed with some of the most challenging diseases facing humankind, like diabetes, obesity, Alzheimer's, cancer and autoimmune disorders. With the progress we've seen to date, we remain extremely confident in our long-term growth prospects.

我們致力於長期投資，以推進有前景的研發機會並支持推出，為被診斷患有人類面臨的一些最具挑戰性的疾病（如糖尿病、肥胖症、阿爾茨海默氏症、癌症和自身免疫性疾病）的患者帶來開創性的療法。隨著我們迄今為止所看到的進展，我們對我們的長期增長前景仍然充滿信心。

Now I'll turn the call over to Kevin to moderate our Q&A session.

現在我將把電話轉給 Kevin 來主持我們的問答環節。

Thanks, Dave. (Operator Instructions) Lois, 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）Lois，請提供問答環節的說明，然後我們為第一個來電者做好準備。

(Operator Instructions) And our first question is from the line of Louise Chen. And she's from Cantor.

（操作員說明）我們的第一個問題來自 Louise Chen。她來自康托爾。

Congratulations on the SURMOUNT data. So I do want to ask you more on tirzepatide and SURMOUNT. How do you see the market landscape for obesity changing in light of your positive SURMOUNT data today? Is there an opportunity to file for that indication with the data? And what's the larger opportunity for you here? Is it type 2 diabetes or obesity?

祝賀 SURMOUNT 數據。所以我想問你更多關於 tirzepatide 和 SURMOUNT 的問題。根據您今天的正面 SURMOUNT 數據，您如何看待肥胖症的市場格局變化？是否有機會使用數據提交該指示？你在這裡有什麼更大的機會？是2型糖尿病還是肥胖？

Thanks, Louise. We'll go to Mike Mason for those.

謝謝，路易絲。我們會去找邁克梅森的。

All right. Louise, thanks for the compliments upfront. We appreciate that. I think the market opportunity is -- kind of remains what we thought before. We see it as a sizable opportunity. And when we look at the -- just the massive numbers of people who live with obesity, over 100 million people in the U.S., 650 million people globally, contributes a burden of over $1 trillion globally, we do think it's a huge opportunity. It should be perceived as a -- and treated as a chronic illness and not only has health implications, but if you live with obesity, it's a very visible disease unlike others that really brings with it some unfortunate stigma in society that really hurts individuals, both physically and emotionally.

好的。路易絲，謝謝你的讚美。我們對此表示讚賞。我認為市場機會 - 有點像我們之前的想法。我們認為這是一個巨大的機會。當我們看到 - 只是大量患有肥胖症的人，美國超過 1 億人，全球 6.5 億人，在全球範圍內造成超過 1 萬億美元的負擔，我們確實認為這是一個巨大的機會。它應該被視為一種 - 並被視為一種慢性疾病，不僅對健康有影響，而且如果你患有肥胖症，它是一種非常明顯的疾病，與其他疾病不同，它確實會在社會上帶來一些真正傷害個人的不幸恥辱，身體上和情感上。

And so there's a need to treat this disease. The market is not going to develop overnight. We have to increase awareness that this is a chronic disease that needs to be treated. We do need to establish and grow the access for it. So we're looking long term to this. I think it's important for us to be able to build the foundation, build the knowledge of this as a chronic disease, get that appreciated by health care professionals and payers and then grow the market. So we're going to look long term. We're investing obviously not only in tirzepatide but early -- many early assets because we do think this is a need in the marketplace that we need to focus on.

所以有必要治療這種疾病。市場不會一蹴而就。我們必須提高對這是一種需要治療的慢性疾病的認識。我們確實需要建立和增加它的訪問權限。因此，我們對此有長期的看法。我認為重要的是我們能夠建立基礎，建立作為一種慢性疾病的知識，得到醫療保健專業人士和支付者的讚賞，然後發展市場。所以我們要著眼長遠。我們顯然不僅投資於 tirzepatide，而且投資於早期 - 許多早期資產，因為我們確實認為這是我們需要關注的市場需求。

And obviously, we're quite delighted by SURMOUNT-1, not only the high dose. I mean, obviously, when we saw the 52 pounds of weight loss at the high dose on average, we were wowed by that. But I'm also as excited about the 16% weight loss at the 5-milligram. Because everyone -- we look at the averages, but there is no averages out there. Every individual is different. And we need to have a medication that at different doses offer different weight loss. And so I'm very pleased about the dose profile and the weight loss profile across all the doses.

顯然，我們對 SURMOUNT-1 感到非常高興，而不僅僅是高劑量。我的意思是，很明顯，當我們看到高劑量平均減重 52 磅時，我們對此感到驚嘆。但我也對 5 毫克體重減輕 16% 感到興奮。因為每個人——我們看平均值，但那裡沒有平均值。每個人都是不同的。我們需要一種不同劑量的藥物可以提供不同的減肥效果。所以我對所有劑量的劑量分佈和體重減輕情況感到非常滿意。

As Dan said, we've originally -- on your filing question, we have aligned with the FDA on four trials, the SURMOUNT-1, 2, 3 and 4 program. But given the huge market need and given this data, we do think it warrants a discussion with the FDA about whether we could find a path to accelerate it to the marketplace to meet this need. The SURMOUNT-1 data is great. We also have over 4,000 patients in the SURPASS-5 global registration studies that provides a lot of good information on the safety and efficacy of tirzepatide in the diabetes population to go along with SURMOUNT-1.

正如 Dan 所說，我們最初 - 在您提交的問題上，我們已與 FDA 在四項試驗（SURMOUNT-1、2、3 和 4 計劃）上保持一致。但鑑於巨大的市場需求和這些數據，我們確實認為有必要與 FDA 討論我們是否可以找到一條加速其進入市場以滿足這一需求的途徑。 SURMOUNT-1 數據很棒。我們在 SURPASS-5 全球註冊研究中也有超過 4,000 名患者，這些研究提供了很多關於替西帕肽與 SURMOUNT-1 一起在糖尿病人群中的安全性和有效性的良好信息。

So we look forward to that conversation. I think when we -- when you look at -- I think your last question was are we more excited about diabetes than obesity? I think we're equally excited about both of them. Obviously, we'll focus our attention on diabetes first, still a huge, massive unmet need with, unfortunately, only half of people who live with type 2 diabetes in good control. So we'll focus on that. And then we'll focus long term on obesity, as I said earlier. So thanks for the question, and thanks for the compliments, appreciate it.

所以我們期待著那次談話。我想當我們——當你看——我認為你的最後一個問題是我們對糖尿病比對肥胖更興奮嗎？我認為我們對他們倆都同樣感到興奮。顯然，我們將首先將注意力集中在糖尿病上，這仍然是一個巨大的、巨大的未滿足需求，不幸的是，只有一半的 2 型糖尿病患者得到了良好的控制。因此，我們將專注於此。然後我們將長期關注肥胖，正如我之前所說。所以謝謝你的問題，謝謝你的讚美，謝謝。

The next caller is Terence Flynn from Morgan Stanley.

下一位來電者是摩根士丹利的特倫斯·弗林。

Great. Let me offer my congratulations as well on the SURMOUNT-1 data. I had two questions. The first is just based on the timing of the acceptance of the tirzepatide BLA for diabetes, it seems like we're past the window for the FDA to convene an AdCom panel. So just wondering if you agree or if the door is still open there.

偉大的。讓我也對 SURMOUNT-1 數據表示祝賀。我有兩個問題。第一個只是基於接受 tirzepatide BLA 治療糖尿病的時間，似乎我們已經過了 FDA 召集 AdCom 小組的窗口。所以只是想知道你是否同意，或者那裡的門是否仍然開著。

And then I was just wondering, probably a question for Mike, if you could share your latest perspectives on commercial positioning of tirzepatide. Is this going to be a single brand or two separate brands? And then how are you thinking early on, just high-level thoughts, about pricing here? Is this going to be based on dose level or fixed as it is with Trulicity?

然後我只是想知道，可能是邁克的一個問題，如果你能分享你對 tirzepatide 商業定位的最新觀點。這將是一個品牌還是兩個獨立的品牌？然後，您在早期是如何考慮這裡的定價的，只是高層次的想法？這將基於劑量水平還是像 Trulicity 一樣固定？

Thanks, Terence. We'll go to Mike for both of those questions.

謝謝，特倫斯。我們將向邁克提出這兩個問題。

Okay. Thanks for the questions. I'll answer your second question first on kind of our commercial positioning. Obviously, for competitive reasons, we'll keep that to ourselves at this time. Know that we will focus on maximizing the opportunity long term in diabetes and obesity. And we'll make the right moves, whether that's one or two brands. We'll have dialogues with the FDA on the one versus two brands. And it's too early to talk about that at this point. With regards to the AdCom, we don't anticipate an AdCom for tirzepatide.

好的。感謝您的提問。我將首先回答您關於我們的商業定位的第二個問題。顯然，出於競爭原因，我們現在將把它留給自己。知道我們將專注於最大限度地提高糖尿病和肥胖症的長期機會。我們會採取正確的行動，無論是一兩個品牌。我們將與 FDA 就一對二品牌進行對話。現在談論這個還為時過早。關於 AdCom，我們預計不會出現替西帕肽的 AdCom。

The next caller is Geoff Meacham from Bank of America.

下一位來電者是美國銀行的 Geoff Meacham。

Also want to offer my congrats on the data. I just had a few on the obesity opportunity. Dan, a question for you, the market gating factor still looks to be reimbursement and access. And I think the prevailing wisdom is that an outcome study will be needed.

也想對數據表示祝賀。我只是有一些肥胖的機會。丹，問你一個問題，市場門控因素看起來仍然是報銷和准入。我認為普遍的看法是需要進行結果研究。

So first, do you agree with that? And second is if you do, how are you guys thinking about the size and scope of an obesity outcome study? I'm not sure if there's a benefit, like a point estimate of a benefit that you think could help drive reimbursement or, for example, bariatric surgery was a reasonable reference point?

那麼首先，你同意嗎？其次，如果你這樣做了，你們如何看待肥胖結果研究的規模和範圍？我不確定是否有好處，例如您認為可以幫助推動報銷的好處的點估計，或者例如減肥手術是一個合理的參考點？

Thanks. We'll go to Dan and then Mike, also invite you to weigh in on our MMO study.

謝謝。我們先去找 Dan，然後是 Mike，還邀請您參與我們的 MMO 研究。

Yes, thanks. Of course, we believe, and there's really quite a bit of evidence, that weight loss will lead to really strong benefits and outcomes across a variety of diseases. Obviously, cardiovascular disease is near the top of the list but many others as well. We know a lot from bariatric surgery, which has shown that it can reverse type 2 diabetes or prevent the onset of diabetes, it can reduce cardiovascular risk. It can decrease even mortality when you get weight loss that's really in the range of what we saw in this trial.

是啊謝謝。當然，我們相信，並且確實有相當多的證據表明，減肥將在各種疾病中帶來非常強大的益處和結果。顯然，心血管疾病位居榜首，但還有許多其他疾病。我們從減肥手術中了解到很多，這表明它可以逆轉 2 型糖尿病或預防糖尿病的發作，它可以降低心血管風險。當您的體重減輕確實在我們在本試驗中看到的範圍內時，它甚至可以降低死亡率。

So we're excited about the potential to change those outcomes. Of course, as you point out, we have to demonstrate that. We will do that over time. But given where we are in our understanding of this disease process and given the depth of unmet medical need in obesity, I don't see that data as a gating factor for use or reimbursement of the drug. Maybe Mike can offer more details on that.

因此，我們對改變這些結果的潛力感到興奮。當然，正如你所指出的，我們必須證明這一點。我們會隨著時間的推移做到這一點。但考慮到我們對這種疾病過程的理解程度以及肥胖症未滿足的醫療需求的深度，我不認為該數據是使用或報銷該藥物的門控因素。也許邁克可以提供更多細節。

Yes, thanks, Dan. Yes, thanks. And thanks for the compliments on the data. Yes, the -- I wouldn't look backwardly at the fact that obesity agents up to this point really haven't been able to secure good access. At the weight loss levels that you were seeing, 5%, 6%, 7% weight loss, no one was able to produce or no one has produced health outcome benefits at that level of weight loss. So it makes sense for payers not opening access for those probably more cosmetic than true health benefits.

是的，謝謝，丹。是啊謝謝。並感謝您對數據的讚美。是的，我不會回過頭來看待肥胖代理到目前為止確實無法獲得良好訪問的事實。在你所看到的減肥水平上，5%、6%、7% 的體重減輕，沒有人能夠產生或沒有人在這種減肥水平上產生健康結果。因此，對於那些可能比真正的健康福利更具美容性的付款人來說，這是有道理的。

But if you're looking at a product like tirzepatide that can deliver up to 22.5% weight loss, we do believe, and there's good data out there, that suggests that's going to really improve and lead to the good health outcomes. We have to produce that over time, and we will do that. But I don't think that will limit us from gaining access in the meantime. I think when you look at Novo's access for Wegovy, they're at 20 million, 25 million people who live with obesity in the U.S. having access. So I think we can continue to build on that. I think there was a real big win for obesity access recently with the federal health employees gaining access for obesity agents. So I think that's an important trend.

但是，如果您正在尋找像 tirzepatide 這樣的產品，它可以減輕高達 22.5% 的體重，我們確實相信，並且那裡有很好的數據，這表明這將真正改善並帶來良好的健康結果。隨著時間的推移，我們必須生產它，我們會這樣做。但我認為這不會限制我們同時獲得訪問權限。我認為，當您查看 Novo 對 Wegovy 的訪問時，他們有 2000 萬、2500 萬在美國患有肥胖症的人可以訪問。所以我認為我們可以在此基礎上繼續發展。我認為最近聯邦衛生人員獲得了肥胖代理的訪問權，肥胖獲得了真正的巨大勝利。所以我認為這是一個重要的趨勢。

Also understand that where we have -- we're dedicated to produce a series of trials that we hope will demonstrate and we expect to demonstrate good outcomes with tirzepatide for sleep apnea, HFpEF as well as our outcome study that will include cardiovascular. Now those are indications right now that do have access. So both Part D, you take sleep apnea, for example, that has good coverage in both commercial and Part D. So we do expect that we show good outcomes there, that for those people who have obesity and sleep apnea, that we should be able to gain access for it. So we think we do believe that access will start off where it is today and grow it over time. But we are committed long term to build access and help people who live with obesity for the duration.

還要了解我們擁有的地方——我們致力於開展一系列試驗，我們希望能夠證明，我們希望通過 tirzepatide 治療睡眠呼吸暫停、HFpEF 以及包括心血管在內的結果研究來證明良好的結果。現在，這些跡象表明現在確實可以訪問。因此，無論是 D 部分，你都以睡眠呼吸暫停為例，它在商業和 D 部分都有很好的覆蓋。所以我們確實希望我們在那裡顯示出良好的結果，對於那些患有肥胖和睡眠呼吸暫停的人，我們應該能夠訪問它。因此，我們認為我們確實相信訪問將從今天的位置開始，並隨著時間的推移而增長。但我們長期致力於建立訪問並在此期間幫助患有肥胖症的人。

The next caller is Chris Schott from JPMorgan.

下一位來電者是摩根大通的 Chris Schott。

Congrats on the data as well. Do you -- I guess, a couple of questions on tirzepatide is, first, do you see weight loss plateauing in the study? And if so, when did it plateau? And then do you expect patients will stay on the drug once they've lost weight? I'm just trying to get a sense of just how you're thinking about duration of tirzepatide in obesity.

也祝賀數據。你 - 我猜，關於 tirzepatide 的幾個問題是，首先，你在研究中看到減肥平台期嗎？如果是這樣，它什麼時候達到穩定狀態？然後，您是否希望患者減肥後會繼續服藥？我只是想了解您如何看待替西帕肽在肥胖中的持續時間。

The second question was on an accelerated filing in obesity. Just any clarity of when we could get more details on that? And then finally, on the prediabetic progression to diabetes endpoint from SURMOUNT-1, I guess, could diabetes prevention become a labeled indication? Or is this just more data that could come on label?

第二個問題是關於肥胖的加速申報。我們什麼時候可以得到更多的細節有什麼明確的嗎？最後，關於從 SURMOUNT-1 的糖尿病前期進展到糖尿病終點，我猜，預防糖尿病會成為一個標記的適應症嗎？還是這只是標籤上可能出現的更多數據？

Thanks, Chris. We'll go to Mike for all those questions.

謝謝，克里斯。所有這些問題我們都會去找邁克。

Okay. I think that may have been more than two, but I'll go through these pretty quickly. So first of all, weight loss plateauing, I think we have to leave some of the data for our medical meetings coming up. So I'll reserve that for that. We do believe that this is a chronic illness that requires chronic treatment. So we do believe people will need to stay on the drug long term in order to get the benefit. And then prediabetes, I look at that as an important population that tirzepatide could provide health outcomes for, so probably more about showing data where a segment could benefit from it versus having a labeled indication for it.

好的。我想這可能不止兩個，但我會很快完成這些。所以首先，減肥平台期，我認為我們必須為即將召開的醫學會議留下一些數據。所以我會為此保留它。我們確實認為這是一種需要長期治療的慢性疾病。因此，我們確實相信人們需要長期服用該藥物才能獲得益處。然後是前驅糖尿病，我將其視為 tirzepatide 可以為其提供健康結果的重要人群，因此可能更多地是關於顯示某個部分可以從中受益的數據，而不是對其進行標記的適應症。

The next caller is Andrew Baum from Citi.

下一位來電者是來自花旗的 Andrew Baum。

A couple of questions, please. The long-term commercial potential of diabetes helped by the comorbidities, I mean, clearly is there. And I'm sure it will be realized by you and your competitors. Could you comment rather on the trajectory near term? You referenced the covered lives that Novo has attained. But obviously, they had a very expensive bridge program during that period, which makes it difficult to extrapolate what the real reimbursed demand is.

有幾個問題，請。我的意思是，糖尿病的長期商業潛力顯然是存在的。我相信你和你的競爭對手都會意識到這一點。您能否評論一下近期的走勢？您提到了 Novo 獲得的涵蓋生活。但很明顯，他們在那段時間有一個非常昂貴的過渡計劃，這使得很難推斷真正的報銷需求是多少。

Separately, we're hearing that PBMs are pushing back as patients are converted from the bridge to reimbursed. So any commentary you have on that would be helpful. And then second, we've had two late-stage failures with SERDs. Given you have a SERD now, I believe, in Phase III as well as obviously having Verzenio, how are you thinking about how this impacts your development of your SERD program?

另外，我們聽說 PBM 正在推遲，因為患者從橋樑轉為報銷。因此，您對此的任何評論都會有所幫助。其次，我們在 SERD 方面遇到了兩次後期失敗。鑑於您現在有一個 SERD，我相信，在第三階段以及顯然有 Verzenio，您如何看待這將如何影響您的 SERD 程序的開發？

Thanks, Andrew. We'll go to Mike for the first one on the trajectory on obesity and then Jake for the question around SERD.

謝謝，安德魯。我們將向 Mike 詢問關於肥胖軌蹟的第一個問題，然後向 Jake 詢問有關 SERD 的問題。

Yes. As I said earlier, I do think it's going to be one that you're not going to probably sprint out of the gate on. You'll have a sizable segment, but one that will grow over time. We will provide supportive care and bridging programs, as you say, at launch to make sure and support people, so they can have a good experience and see the benefits of the weight loss. But we do think it's something that -- this is one that I would look at the obesity market, one that we'll establish. It will be decent size, but it will grow for the next decade or 2.

是的。正如我之前所說，我確實認為這將是一個你可能不會衝出大門的比賽。您將擁有一個相當大的細分市場，但會隨著時間的推移而增長。正如您所說，我們將在啟動時提供支持性護理和過渡計劃，以確保和支持人們，使他們能夠獲得良好的體驗並看到減肥的好處。但我們確實認為這是——這是我要研究的肥胖市場，我們將建立的市場。它將是不錯的規模，但它會在未來十年或兩年內增長。

Thanks, Mike. Jake?

謝謝，邁克。傑克？

Yes, thanks for the question about SERDs. Our view of our program and the landscape hasn't really changed all that much in light of the recent announcements. Obviously, as it relates to the two most recent trial readouts, we've yet to see the actual data. But at least in one case, there were some directional clues given by company management. I think largely speaking, we saw those studies as sort of underpowered Phase II trials. And I think in many cases, what we're hearing qualitatively from those companies suggests exactly that, in other words, trends in the right direction but underpowered studies.

是的，感謝有關 SERD 的問題。鑑於最近的公告，我們對我們的計劃和景觀的看法並沒有真正改變太多。顯然，由於它與最近的兩個試驗讀數有關，我們還沒有看到實際數據。但至少在一個案例中，公司管理層給出了一些方向性的線索。我認為總的來說，我們認為這些研究是一種動力不足的 II 期試驗。而且我認為在許多情況下，我們從這些公司那裡聽到的定性信息恰恰表明，換句話說，趨勢是朝著正確的方向發展，但研究力度不足。

Our initial second-line randomized trial that we're recruiting right now is a fully powered Phase III study. So if anything, we're actually more confident in that study winning than we were previously. But that's not really the -- that may be the first path to market for the agent and impactful for those patients in the late line setting. But that's not really the ultimate, I think, most impactful place for the medicine, which is really in the adjuvant setting. And we're working on a trial design there that we'll talk more about later this year.

我們現在正在招募的最初的二線隨機試驗是一項全面的 III 期研究。因此，如果有的話，我們實際上比以前更有信心在那項研究中獲勝。但這並不是真正的——這可能是該藥物進入市場的第一條途徑，並且對那些處於後期線設置的患者有影響。但這並不是真正的最終，我認為，對藥物最有影響的地方，它實際上是在輔助環境中。我們正在那裡進行試驗設計，我們將在今年晚些時候進行更多討論。

The next caller is Seamus Fernandez from Guggenheim.

下一位來電者是來自古根海姆的 Seamus Fernandez。

Congrats on the data. Just a quick question, Dan. This is a very large Phase III program that you're conducting in obesity and more broadly. But the statement that you will be pursuing a potential faster path to market with regulatory authorities on the basis of SURMOUNT-1 data is certainly intriguing. How do you see the likelihood of success? And is the real separation there the 20% threshold? Do you really think that's the potential game-changer? Or is it something else in the data that we have yet to see that you think is uniquely compelling?

恭喜數據。只是一個簡單的問題，丹。這是一個非常大的 III 期計劃，您在肥胖症和更廣泛的範圍內進行。但是，您將在 SURMOUNT-1 數據的基礎上與監管機構一起尋求一條潛在的更快上市途徑的聲明當然很有趣。您如何看待成功的可能性？真正的分離是 20% 的門檻嗎？你真的認為這是潛在的遊戲規則改變者嗎？或者是我們還沒有看到的數據中的其他東西，你認為它具有獨特的吸引力？

And then separately, just wanted to follow up on the -- your comments on the Alzheimer's side of things. I think you've said in the past that there are some issues as it relates to how we think about the impact or thoughts around other clinical trials. Wondering how you're feeling along those lines and really just wanted to get your general sort of compare and contrast of the Lilly program versus some of those -- of the other two programs that are coming later this year.

然後分別，只是想跟進您對阿爾茨海默氏症方面的評論。我認為您過去曾說過，存在一些問題，因為它與我們如何看待其他臨床試驗的影響或想法有關。想知道您在這些方面的感受如何，並且真的只是想對 Lilly 計劃與今年晚些時候推出的其他兩個計劃中的一些計劃進行一般比較和對比。

Thanks, Seamus. We'll go to Dan for both of those.

謝謝，西莫。我們會去丹為這兩個。

Okay. Sure, Seamus. Let me start with tirzepatide and sort of the comments that I made on the regulatory path. The FDA has clear guidance on what's required to get an indication for an antiobesity drug. And those guidance documents form the basis of our previous discussions and alignment with the agency. Our base case based on those has been and really continues to be the submission will require the full package of Phase III data from this trial -- from this program. On the other hand, as I said, I think we were impressed and delighted with the data that we got from SURMOUNT-1. It's a very large Phase III trial, as you pointed out. And there are a number of elements here that encourage us to open the door for additional discussion with the FDA.

好的。當然，西莫。讓我從 tirzepatide 和我對監管路徑的評論開始。 FDA 對獲得抗肥胖藥物適應症所需的條件有明確的指導。這些指導文件構成了我們之前討論和與該機構保持一致的基礎。我們基於這些的基本案例已經並且實際上將繼續是提交將需要來自該試驗的完整的 III 期數據包 - 來自該計劃。另一方面，正如我所說，我認為我們對從 SURMOUNT-1 獲得的數據印象深刻和高興。正如你所指出的，這是一個非常大的 III 期試驗。這裡有許多因素鼓勵我們打開大門，與 FDA 進行更多討論。

You asked what is it specifically? Maybe I'll highlight two or three things. First, the efficacy, as you pointed out, the more than 20% weight loss, is really unprecedented level of weight loss in the field. And I think that's exciting for patients and addressing a very significant unmet medical need. Second is the safety and tolerability data that we got that I think there's a pleasant surprise there if you look at how well tolerated this drug was, how few discontinuations we had and, as I pointed out, more discontinuations from treatment on placebo, many more than on the active arms of the drug, just indicating that people tolerate this or want to stay on the drug and appreciate the weight loss benefits they're getting.

你問具體是什麼？也許我會強調兩三件事。一、功效，正如你所指出的，20%以上的減肥效果，在減肥領域確實是史無前例的水平。我認為這對患者來說是令人興奮的，並解決了一個非常重要的未滿足的醫療需求。其次是我們獲得的安全性和耐受性數據，我認為如果你看看這種藥物的耐受性有多好，我們停藥的次數有多少，以及正如我所指出的，更多的安慰劑治療中止，還有更多而不是在藥物的主動臂上，只是表明人們可以忍受這種情況或想要繼續服用藥物並欣賞他們所獲得的減肥益處。

So the very good safety and tolerability profile that we're seeing, combined with the extraordinary efficacy profile, I think, is a major step in that argument. The last piece, of course, is we don't see this data in isolation. This builds on a very significant type 2 diabetes program, which, of course, involve many patients with type 2 diabetes and obesity and demonstrated safety and efficacy in that setting as well. So we'll see how that goes. And I think to circle back to Chris' question, when do we learn more? As we have discussions with regulators, if we learn more and we see that there is an opportunity for expedited path here, we'll be as forthcoming with investors as possible.

因此，我認為，我們所看到的非常好的安全性和耐受性概況，以及非凡的療效概況，是該論點的重要一步。當然，最後一點是我們不會孤立地看到這些數據。這建立在一個非常重要的 2 型糖尿病計劃的基礎上，當然，該計劃涉及許多患有 2 型糖尿病和肥胖症的患者，並且在該環境中也證明了安全性和有效性。所以我們會看看情況如何。我想回到克里斯的問題，我們什麼時候能學到更多？當我們與監管機構進行討論時，如果我們了解更多信息並且我們看到這裡有加快路徑的機會，我們將盡可能地與投資者相處。

Your second question here was around Alzheimer's and where are we thinking about our profile versus competitors and when those competitor readouts, what are we going to be looking at. I think we have a number of design elements in TRAILBLAZER-2 that we've spoken about previously that, we think, could be very important, probably starting with our use of biomarkers to select patients, not just amyloid positivity but also windowing in on patients with what we call intermediate tau levels. So these aren't patients who have too much tau in the brain because we think they're beyond the point where anti-amyloid drugs will help them nor are they patients with no tau in the brain because we think those patients won't progress even on placebo and therefore won't get benefit from a drug.

你的第二個問題是關於阿爾茨海默氏症的，我們在哪裡考慮我們的個人資料與競爭對手的對比，以及當這些競爭對手讀出時，我們將關注什麼。我認為我們在 TRAILBLAZER-2 中有許多我們之前談到過的設計元素，我們認為這可能非常重要，可能從我們使用生物標誌物來選擇患者開始，不僅是澱粉樣蛋白陽性，而且還有窗口化我們稱之為中間 tau 水平的患者。所以這些不是大腦中 tau 過多的患者，因為我們認為他們超出了抗澱粉樣蛋白藥物可以幫助他們的程度，也不是大腦中沒有 tau 的患者，因為我們認為這些患者不會進展即使在安慰劑上，因此也不會從藥物中受益。

So we think selecting those patients will give us the opportunity to see better efficacy on a more homogenous background. Second, we think we have a drug that lowers amyloid faster and to a deeper degree. And that should translate to improved benefits. And then third is some of the statistical differences in our analysis plan, focusing on a compositive measure, iADRS, which we're excited about and think should be more highly powered to see a larger effect size. So all of those things combined lead us to a point where even if competitors trials are negative, and I think there's a reasonable chance one or both could be, we won't be discouraged.

因此，我們認為選擇這些患者將使我們有機會在更同質的背景下看到更好的療效。其次，我們認為我們有一種藥物可以更快、更深入地降低澱粉樣蛋白。這應該轉化為改善的好處。然後第三個是我們分析計劃中的一些統計差異，重點是綜合衡量指標 iADRS，我們對此感到興奮並認為應該更有能力看到更大的影響大小。因此，所有這些因素加在一起使我們達到了這樣一個點，即使競爭對手的試驗是負面的，而且我認為有一個或兩個都是負面的合理機會，我們也不會氣餒。

What I expect to see though is when we look at the totality of data from competitor readouts prior to ours, we will see evidence that lowering amyloid in general is having a positive effect on slowing cognition and function. Even if some trials on some endpoints at some time points hit or don't hit statistical significance, I think it's the totality data that will encourage us. And then as I said, our trial is designed to hit. So that's what we're hoping for and that's what we expect middle of next year.

不過，我希望看到的是，當我們查看之前競爭對手讀數的全部數據時，我們將看到證據表明，降低澱粉樣蛋白總體上對減緩認知和功能具有積極作用。即使在某些時間點在某些端點上進行的一些試驗達到或沒有達到統計顯著性，我認為這是鼓勵我們的總體數據。然後正如我所說，我們的試驗旨在打擊。所以這就是我們所希望的，也是我們期望明年年中的。

The next caller is Tim Anderson from Wolfe Research.

下一位來電者是來自 Wolfe Research 的 Tim Anderson。

Congrats on the data. This is Alice Nettleton on for Tim Anderson. So just on tirzepatide, for both your product and Novo's Wegovy, the weight loss is impressive. But with both products, there's still about 30% to 40% of patients in placebo who don't achieve at least 5% weight reduction, which is quite a high percentage. And it almost seems to suggest the resistance mechanism of some sort to GLP and GIP. So is there any mechanistic rationale or predictability for those who don't respond?

恭喜數據。這是蒂姆安德森的愛麗絲內特爾頓。因此，僅使用 tirzepatide，對於您的產品和 Novo 的 Wegovy，減肥效果都令人印象深刻。但是對於這兩種產品，仍然有大約 30% 到 40% 的安慰劑患者沒有達到至少 5% 的體重減輕，這是一個相當高的百分比。它似乎暗示了某種對 GLP 和 GIP 的耐藥機制。那麼對於那些沒有回應的人來說，是否有任何機械原理或可預測性？

Thanks. We'll go to Dan for that question.

謝謝。我們會去找丹回答這個問題。

Yes. Thanks for that question. I think you're right, in past studies of different medications for weight loss, there have been a lot of patients who didn't respond. That's not the case with tirzepatide. So we're really delighted that at the 10- and 15-milligram dose, more than 96% of patients had at least 5% weight loss. So this drug is working, to some extent, in the vast majority of patients in this trial.

是的。謝謝你的問題。我認為你是對的，在過去對不同減肥藥物的研究中，有很多患者沒有反應。替西帕肽並非如此。所以我們真的很高興在 10 和 15 毫克的劑量下，超過 96% 的患者體重減輕了至少 5%。因此，這種藥物在某種程度上對本試驗中的絕大多數患者都有效。

And nearly 2/3 of the patients with the highest dose are getting 20% weight loss, which is really a life-changing level. So I think you're right, patients have variable degrees of resistance to antiobesity mechanisms. But I also think that this combination of GIP and GLP that we have in tirzepatide is such a powerful mechanism that it overcomes those resistant patients for the most part.

最高劑量的患者中有近 2/3 的患者體重減輕了 20%，這確實是一個改變生活的水平。所以我認為你是對的，患者對抗肥胖機制有不同程度的抵抗。但我也認為，我們在 tirzepatide 中的這種 GIP 和 GLP 組合是如此強大的機制，它在很大程度上克服了那些耐藥患者。

The next caller is Umer Raffat from Evercore.

下一位來電者是 Evercore 的 Umer Raffat。

Congrats on the data. So donanemab, I have two questions. One, have you been able to finalize the stack line with FDA? And also, given your confidence in donanemab, I'm curious why it would not make sense to have a CDR Sum of Boxes endpoint in there in TRAILBLAZER-4, the head-to-head versus aducanumab.

恭喜數據。所以donanemab，我有兩個問題。一，您是否能夠最終確定與 FDA 的堆棧線？而且，鑑於您對 donanemab 的信心，我很好奇為什麼在 TRAILBLAZER-4 中使用 CDR Sum of Boxes 端點沒有意義，即頭對頭與 aducanumab。

And then separately, just a quick one, I noticed in your slides, you mentioned the IL-2 conjugate in ulcerative colitis is being removed. And I couldn't tell if it's being discontinued in that because this trial has barely started less than 6 months ago, so just thought I should clarify.

然後分開，只是一個快速的，我在你的幻燈片中註意到，你提到潰瘍性結腸炎中的 IL-2 結合物正在被去除。我不知道它是否已經停止，因為這個試驗在不到 6 個月前才剛剛開始，所以我想我應該澄清一下。

Thanks. We'll go to Dan for all those questions.

謝謝。所有這些問題我們都會去找丹。

Yes, sure. So let me start with the Alzheimer's questions. I think we've been public about our stats plan. I think the focus on iADRS is well warranted by all of the data that we've collected by pretty detailed statistical analyses, many of which have been published on past trials, which just show this is an outcome that performs better from a statistical perspective than things like CDR Sum of Boxes while still capturing both function and cognition. So CDR is noisy and also appears unreliable. If you look across sister studies, for example, the two solanezumab studies or the two aducanumab studies, CDR Sum of Boxes can move in opposite directions in different studies whereas ADLs and ADAS-Cog, the two components of iADRS are much more reliable, move together, show consistent effects.

是的，當然。所以讓我從阿爾茨海默氏症的問題開始。我認為我們已經公開了我們的統計計劃。我認為我們通過非常詳細的統計分析收集的所有數據都充分證明了對 iADRS 的關注，其中許多數據已在過去的試驗中發表，這表明從統計角度來看，這是一個比諸如 CDR Sum of Boxes 之類的東西，同時仍然捕獲功能和認知。所以 CDR 很嘈雜，也顯得不可靠。如果您查看姊妹研究，例如，兩項 solanezumab 研究或兩項 aducanumab 研究，CDR Sum of Boxes 在不同研究中可以向相反方向移動，而 ADL 和 ADAS-Cog，iADRS 的兩個組成部分更可靠，移動一起，顯示出一致的效果。

So that's where we are. I think it's an evolution of endpoints. And we'll do our best to justify that with regulators once we have our data. Why wouldn't we have CDR Sum of Boxes was the second part of your question. Well, of course, we do. It's -- it will be a gated secondary for sure. And I think from our perspective, the worst-case scenario is that we're held to achieving iADRS and CDR Sum of Boxes. That's okay. If that happens, I hope and expect that we'll have a good chance to hit CDR Sum of Boxes. But of course, we're going to put what we see as the least noisy, most reliable, most informative endpoint first in our statistical analysis, which is iADRS.

這就是我們所在的位置。我認為這是端點的演變。一旦我們獲得數據，我們將盡最大努力向監管機構證明這一點。為什麼我們沒有 CDR Sum of Boxes 是您問題的第二部分。嗯，當然，我們這樣做。這是 - 它肯定會是一個封閉的中學。而且我認為從我們的角度來看，最壞的情況是我們堅持要實現 iADRS 和 CDR Sum of Boxes。沒關係。如果發生這種情況，我希望並期待我們有很好的機會達到 CDR Sum of Boxes。但是，當然，我們將把我們認為噪音最小、最可靠、信息最多的端點放在我們的統計分析的首位，即 iADRS。

With respect to IL-2, you're right, this was a pretty fast in-and-out in ulcerative colitis. We were pleased to enroll this Phase II study pretty quickly. We triggered an interim analysis based on a certain number of patients with a certain amount of follow-up. And based on that analysis and prespecified criteria, we did not see enough efficacy to proceed. So it failed that futility analysis. We dropped that indication, wind down that particular study in ulcerative colitis, but two other indications persist.

關於 IL-2，你是對的，這在潰瘍性結腸炎中是一個相當快的進出。我們很高興很快就參加了這項 II 期研究。我們根據一定數量的患者和一定數量的隨訪觸發了中期分析。根據該分析和預先指定的標準，我們沒有看到足夠的療效繼續進行。所以它沒有通過無效分析。我們放棄了該適應症，結束了潰瘍性結腸炎的特定研究，但其他兩個適應症仍然存在。

The next caller is Steve Scala from Cowen.

下一位來電者是來自 Cowen 的 Steve Scala。

A couple of questions. The SURMOUNT-1 data was very impressive but not a huge surprise. It must have been considered as a likely scenario by Lilly, yet Lilly's filing strategy has shifted. So just to be clear, has FDA or other regulatory body encouraged Lilly to file early based on the SURMOUNT-1 results? So that's the first question.

幾個問題。 SURMOUNT-1 的數據令人印象深刻，但並不令人意外。禮來公司一定認為這是一種可能的情況，但禮來公司的備案策略已經發生了變化。所以要明確一點，FDA 或其他監管機構是否鼓勵禮來根據 SURMOUNT-1 結果提早提交申請？所以這是第一個問題。

Second question is were there any inventory movements or other unusual movements in the quarter? It seems that a number of your key drivers just missed at least our thinking. So I'm wondering if it was inventory movements that accounted for that.

第二個問題是本季度是否有任何庫存變動或其他異常變動？似乎您的一些關鍵驅動因素至少錯過了我們的想法。所以我想知道是否是庫存變動導致了這一點。

Thanks, Steve. We'll go to Dan for the regulatory question and then Anat for the question on inventory.

謝謝，史蒂夫。我們將向 Dan 詢問監管問題，然後向 Anat 詢問有關庫存的問題。

All right, Steve, I think you said it's not a surprise. I think there are some things here that are quite a bit more positive than maybe most people would have expected. Certainly, the level of efficacy here that was achieved was, I think, higher than most expectations as well as the tolerabilities of the adverse events from nausea, diarrhea, vomiting, lower probably than what most people would have expected. Treatment discontinuation is particularly lower. So I think on the whole, we have a data package that does exceed expectations.

好吧，史蒂夫，我想你說這並不奇怪。我認為這裡有些事情比大多數人預期的要積極得多。當然，我認為這裡實現的療效水平高於大多數人的預期，噁心、腹瀉、嘔吐等不良事件的耐受性可能低於大多數人的預期。治療中斷特別低。所以我認為總的來說，我們有一個超出預期的數據包。

So it's really at the top end of the range of what we thought might be possible for a drug like tirzepatide. So we're excited about that. Specifically, you're asking about regulatory interactions. We usually don't want to get into like back and forth on things like that. But just to be clear, as I said before, our alignment with the FDA was around submitting when the full package is complete and have not had discussions yet about what other options might exist in light of this data.

因此，它確實處於我們認為對於像 tirzepatide 這樣的藥物可能的範圍的頂端。所以我們對此感到興奮。具體來說，您是在詢問監管互動。我們通常不想在這樣的事情上來回糾纏。但需要明確的是，正如我之前所說，我們與 FDA 的一致是在完整的包裹完成時提交，並且尚未討論根據這些數據可能存在哪些其他選擇。

Thanks, Dan. Anat?

謝謝，丹。阿納特？

So for the dynamics in Q1, we typically see a dynamic associated with inventory build at the end of each calendar year in December and then following by inventory burn typically in the first quarter of each year. We saw the same dynamic here this year. We saw an impact in Trulicity and a number of other products, which you may be seeing as you're looking at year-on-year comparison.

因此，對於第一季度的動態，我們通常會在每年 12 月的每個日曆年末看到與庫存增加相關的動態，然後通常在每年第一季度出現庫存消耗。今年我們在這裡看到了同樣的動態。我們看到了 Trulicity 和許多其他產品的影響，當您查看年度比較時，您可能會看到這些影響。

The other element, if you're looking at Taltz from a year-on-year perspective, we did see in Q1, in comparison to Q1 of 2021, reduction in script size. As you recall, last year, we had -- we started our contract with ESI and the loading dose was associated with multiple devices that each patient started on. So this quarter, we're just seeing a reduction associated with that year-on-year comparison.

另一個因素，如果你從同比的角度來看 Taltz，與 2021 年第一季度相比，我們確實在第一季度看到了腳本大小的減少。您還記得，去年，我們與 ESI 簽訂了合同，負荷劑量與每位患者開始使用的多個設備相關聯。所以本季度，我們只是看到與去年同期比較相關的減少。

The next caller is Vamil Divan from Mizuho.

下一位來電者是來自瑞穗的 Vamil Divan。

Maybe a couple more on the obesity side, if I could. So one, you mentioned the amylin agonist that you've moved into Phase I here. Can you just maybe talk about that? Is that maybe more of an insurance policy against what competitors are working on? Or do you sort of expect the amylin could maybe accompany some other mechanisms' additional efficacy on top of what we're seeing now with the GLPs and also with tirzepatide?

如果可以的話，也許在肥胖方面還有更多。所以，你提到了你已經進入第一階段的胰淀素激動劑。你能談談嗎？這可能更像是針對競爭對手正在研究的保險政策嗎？或者您是否期望糊精可能會伴隨一些其他機制的額外功效，除了我們現在看到的 GLP 和 tirzepatide 嗎？

And then second, you talked about this a little bit before around the discontinuation and the duration. So can you just remind us what the current duration or average duration therapy is with Trulicity and then maybe if you have any sort of current assumptions of how you -- or when you think patients may end up staying in a product like tirzepatide, given the superior profile we're seeing for that, either for diabetes and/or obesity?

其次，您在停產和持續時間之前談到了這一點。那麼，您能否提醒我們 Trulicity 目前的治療持續時間或平均持續時間是多少，然後如果您對您的方式有任何當前的假設 - 或者您認為患者最終可能會留在像 tirzepatide 這樣的產品中，考慮到我們看到的優越形象，無論是糖尿病和/或肥胖症？

Thanks, Vamil. We'll go to Dan for the question on kind of early phase obesity and then we'll go to Mike for the question around Trulicity duration and implications in obesity.

謝謝，瓦米爾。我們將向 Dan 詢問有關早期肥胖的問題，然後我們將向 Mike 詢問有關 Trulicity 持續時間和對肥胖的影響的問題。

Thanks, Vamil. You're asking about our long-acting amylin agonist here. We've been interested in biology of other incretins and incretin-like pathways for many years, maybe a decade now or more. is one of those pathways we've worked on dual amylin calcitonin receptor agonist. This is a pure amylin agonist. We're exploring these and other similar mechanisms as complements likely to tirzepatide. I don't expect any of these mechanisms to offer this kind of weight loss, 22.5% weight loss. But I think it may be for some patients who desire even additional weight loss that you could stack one of these mechanisms on top of tirzepatide.

謝謝，瓦米爾。您在這裡詢問我們的長效胰淀素激動劑。多年來，我們一直對其他腸促胰島素和腸促胰島素樣通路的生物學感興趣，現在可能是十年或更長時間。是我們研究雙胰淀素降鈣素受體激動劑的途徑之一。這是一種純胰淀素激動劑。我們正在探索這些和其他類似的機制，作為替西帕肽的補充。我不指望這些機制中的任何一種能提供這種減肥效果，22.5% 的減肥效果。但我認為對於一些希望進一步減輕體重的患者來說，您可以將其中一種機制疊加在 tirzepatide 之上。

But clearly, we've raised the bar. And we'll look through our Phase I and Phase II portfolio now with even higher criteria for progressing. I think a new weight loss mechanism now is going to have to be in the very high 20s, I think, to be an exciting advance beyond tirzepatide. Maybe adding something to tirzepatide could accomplish that and offer the majority of patients efficacy similar or even better to bariatric surgery. That's the next frontier.

但很明顯，我們提高了標準。現在，我們將以更高的標準審視我們的第一階段和第二階段投資組合。我認為現在一種新的減肥機制必須達到 20 多歲，我認為，這是超越 tirzepatide 的令人興奮的進步。也許在 tirzepatide 中添加一些東西可以實現這一目標，並為大多數患者提供與減肥手術相似甚至更好的療效。那是下一個邊界。

Thanks, Dan. Mike?

謝謝，丹。麥克風？

Yes, thanks for the question. It's a very good question. The -- when you look at diabetes versus obesity, it's hard to compare, I think, to suggest that because of the nature of the diseases that you'll have like similar discontinuation rates or length of therapy. When you look at when someone starts Trulicity in type 2 diabetes, they only have a fraction of the beta cell health of someone who's normal before the onset and the run-up of prediabetes and diabetes has lowered the functioning of the beta cell. And so what you have in diabetes is that beta cell health continues to decline. And then at some point, you may have to go on insulin.

是的，謝謝你的提問。這是一個很好的問題。 - 當你看糖尿病和肥胖時，我認為很難比較，因為疾病的性質，你會喜歡相似的停藥率或治療時間。當您查看某人何時開始使用 Trulicity 治療 2 型糖尿病時，他們的 β 細胞健康狀況只有發病前正常人的一小部分，而且前驅糖尿病和糖尿病的升高降低了 β 細胞的功能。所以你在糖尿病中所擁有的是β細胞健康繼續下降。然後在某些時候，你可能不得不繼續使用胰島素。

We don't believe that we'll have that same dynamic in obesity that the effect of weight loss with someone who lives with obesity is not going to have that same effect of kind of wearing off with the beta cell health that you see for Trulicity and our GLPs in diabetes. So we do believe that the weight loss will be more durable and that patients will be well motivated to stay on therapy. That said, it will be an area of focus for us to make sure that we learn why people stop taking obesity agents. And we'll do whatever we can to support patients during the entire length of therapy.

我們不相信我們會在肥胖方面有同樣的動態，即對於患有肥胖症的人來說，減肥的效果不會像你在 Trulicity 中看到的那樣對 β 細胞健康產生同樣的影響和我們在糖尿病中的 GLP。因此，我們確實相信體重減輕會更加持久，並且患者將有很好的動力繼續接受治療。也就是說，確保我們了解人們停止服用肥胖藥物的原因將是我們關注的一個領域。我們將盡我們所能在整個治療期間為患者提供支持。

The next caller is Carter Gould from Barclays.

下一位來電者是來自巴克萊的 Carter Gould。

This is Justin on for Carter. And congrats on all the exciting updates today. The first one, sort of looking at read-throughs to heart failure, I just wanted to get your thoughts on the implications of your SURMOUNT data on the ongoing SUMMIT study, given that weight loss is a predictor of outcomes there. Does the magnitude of weight loss today sort of increase your confidence in the outcomes of that study? And then are there any interim analyses we should be looking for out of SUMMIT?

這是卡特的賈斯汀。並祝賀今天所有令人興奮的更新。第一個是對心力衰竭的通讀，我只是想了解您的 SURMOUNT 數據對正在進行的 SUMMIT 研究的影響，因為減肥是那裡結果的預測指標。今天減肥的幅度是否會增加你對該研究結果的信心？那麼我們應該從 SUMMIT 中尋找任何中期分析嗎？

Okay, thank you. We'll go to Mike for those questions on SUMMIT.

好的謝謝。我們將在 SUMMIT 上向 Mike 詢問這些問題。

Yes. I mean, good question. I mean, I think the strength of the SURMOUNT-1 data makes us confident in the entire tirzepatide Phase III program for all indications. And so obviously, our hypothesis -- one of the hypothesis was weight loss would help individuals with HFpEF. And obviously, SURMOUNT-1 supported that. So yes, we're confident in our HFpEF program for tirzepatide. I don't believe we have, and maybe Dan can answer that question, off the top of my head. But I don't believe we have any interim readouts on our heart failure study.

是的。我的意思是，好問題。我的意思是，我認為 SURMOUNT-1 數據的強度使我們對所有適應症的整個 tirzepatide III 期計劃充滿信心。很明顯，我們的假設——其中一個假設是減肥會幫助患有 HFpEF 的人。顯然，SURMOUNT-1 支持這一點。所以，是的，我們對我們的 HFpEF 替西帕肽項目充滿信心。我不相信我們有，也許丹可以在我腦海中回答這個問題。但我不相信我們有任何關於心力衰竭研究的中期讀數。

Yes, Mike, we usually try not to disclose potential interims to preserve the integrity of the study. So sometimes we build those options in and sometimes we'll not. But I totally agree that this weight loss sort of at the high end of expectations, as I said earlier, has just got to increase our confidence in HFpEF. And of course, as we dig deeper, we'll look at a number of biomarkers in the study, which could further inform cardiovascular benefits.

是的，邁克，為了保持研究的完整性，我們通常盡量不透露潛在的臨時信息。所以有時我們會建立這些選項，有時我們不會。但我完全同意，正如我之前所說的那樣，這種減肥方式處於預期的高端，只是增加了我們對 HFpEF 的信心。當然，隨著我們深入研究，我們將研究研究中的一些生物標誌物，它們可以進一步告知心血管益處。

The next caller is Kerry Holford from Berenberg.

下一位來電者是來自 Berenberg 的 Kerry Holford。

Another one on tirzepatide first. So if the compelling data today enables an earlier filing in obesity, are you also now hoping to secure a quick review? Do you think that, that would -- you would get that as a supplementary filing or perhaps you would look to use the PRV that you purchased this quarter? And can you also just confirm the exact PDUFA date for the diabetes filing?

另一個先用替西帕肽。因此，如果今天令人信服的數據能夠更早地提交肥胖問題，您現在是否也希望獲得快速審查？你認為那會 - 你會得到它作為補充文件，或者你可能會考慮使用你本季度購買的 PRV？您也可以確認糖尿病申報的確切 PDUFA 日期嗎？

And then my second question for you, Anat, on IPR&D and guidance. Clearly, this cost could evolve [within the year] if you make further acquisitions, collaborations and so on. But can we expect you to provide visibility at the start of each year on what extent or level of milestones you believe are likely to be paid in the years ahead?

然後我要問你的第二個問題，Anat，關於 IPR&D 和指導。顯然，如果您進行進一步的收購、合作等，這一成本可能會在[年內]發生變化。但是，我們能否期望您在每年年初就您認為未來幾年可能支付的里程碑的程度或水平提供可見性？

Thanks, Kerry. We'll go to Dan for the questions around regulatory filing around tirzepatide and then again to Anat on IPR&D and guidance.

謝謝，克里。我們將向 Dan 詢問有關 tirzepatide 的監管備案問題，然後再向 Anat 詢問有關 IPR&D 和指導的問題。

Yes. Thanks, Kerry. Just to clarify, we didn't announce plans for an early filing here. We just said we're moving to the next step and discussing options with regulators. You're right, we do have a PRV voucher that we purchased. We're excited to have a portfolio rich with opportunities, both new molecular entities as well as the new indications, such as the obesity indication. We'll choose based on regulatory paths that are available to us and unmet medical needs and competition, of course, what's the best opportunity to use that voucher on.

是的。謝謝，克里。只是為了澄清一下，我們沒有在這裡宣布提前提交的計劃。我們剛剛說過我們正在進入下一步並與監管機構討論選項。你是對的，我們確實有我們購買的 PRV 代金券。我們很高興擁有一個充滿機會的產品組合，包括新的分子實體以及新的適應症，例如肥胖適應症。我們將根據我們可用的監管路徑以及未滿足的醫療需求和競爭進行選擇，當然，使用該憑證的最佳機會是什麼。

Thanks, Dan. Anat?

謝謝，丹。阿納特？

Kerry, so on the IPR&D charges, while we're now building them into our non-GAAP actuals -- and we'll provide information, not just on the quarterly results but anything -- any business development transactions that had been signed between the end of the quarter in our earnings call. But if you look even at our numbers from last year, these numbers are highly variable and highly unpredictable. So you can move from $40 million in 1 quarter to $400 million in another quarter or even 0.

克里，所以關於 IPR&D 費用，而我們現在正在將它們構建到我們的非 GAAP 實際值中——我們將提供信息，不僅僅是季度業績，而是任何東西——任何已經簽署的業務發展交易本季度末在我們的收益電話會議上。但如果你看看我們去年的數字，這些數字是高度可變且高度不可預測的。所以你可以從一個季度的 4000 萬美元上升到另一個季度的 4 億美元，甚至是 0 美元。

And when we issue guidance, it is practically impossible for us to provide any detailed view on what those charges will be, not knowing what business development transaction we'll be signing. So what we will do is as we have those, we'll provide that information to the investment community every quarter. Typically, if it's associated with a large business development transaction, there will be a press release associated with it within the quarter. So you'll be able to see and track that. But providing it as part of guidance is challenging. It's practically impossible actually to predict these.

而且，當我們發布指南時，我們幾乎不可能提供任何關於這些費用的詳細信息，不知道我們將簽署什麼業務發展交易。因此，我們將做的是，我們將在每個季度向投資界提供這些信息。通常，如果它與大型業務開發交易相關聯，則將在本季度發布與之相關的新聞稿。因此，您將能夠看到並跟踪它。但是將其作為指導的一部分提供是具有挑戰性的。實際上，要預測這些實際上是不可能的。

Thanks, Anat. And Kerry, you had a question on the type 2 diabetes PDUFA. We don't give PDUFA dates. We announce in the quarter when we submitted it. But we -- as we said, we expect that by mid-year.

謝謝，阿納特。 Kerry，你有一個關於 2 型糖尿病 PDUFA 的問題。我們不提供 PDUFA 日期。我們在提交時的季度公佈。但是我們 - 正如我們所說，我們預計到年中。

The next caller is Evan Seigerman from BMO.

下一位來電者是 BMO 的 Evan Seigerman。

Would love to know if you have any additional color as to why we saw a higher discontinuation rate in the mid-dose of the tirzepatide data. And then more broadly speaking, when you think about the market between Trulicity and potentially tirzepatide, do you expect to switch patients over? How do you expect these two assets to coexist, assuming approval of tirzepatide?

很想知道您是否對我們為什麼在 tirzepatide 數據的中間劑量中看到更高的停藥率有任何額外的看法。然後更廣泛地說，當您考慮 Trulicity 和潛在的 tirzepatide 之間的市場時，您是否希望轉換患者？假設 tirzepatide 獲得批准，您如何期望這兩種資產共存？

Thanks, Evan. We'll go to Dan for the first question around tolerability and discontinuations and then Mike for the second one on Trulicity and tirzepatide.

謝謝，埃文。我們將向 Dan 詢問關於耐受性和停藥的第一個問題，然後向 Mike 詢問關於 Trulicity 和 tirzepatide 的第二個問題。

Yes. Thanks. In the study, the tolerability of the 10- and 15-milligram doses were pretty similar. So it's not surprising the treatment discontinuation rates could have been pretty similar. Of course, there's a little bit more efficacy on the 15-milligram dose, which is an important driver to stay on therapy. So you probably see the balance of tolerability and efficacy playing out a little bit better perhaps in the 15 than the 10. But these are these are all pretty small rates of discontinuation. If you look at the sort of mid-single-digit rates of discontinuation for AEs, that's really great, I think, better than expected.

是的。謝謝。在這項研究中，10 毫克和 15 毫克劑量的耐受性非常相似。因此，治療中止率可能非常相似也就不足為奇了。當然，15 毫克劑量的療效會更高一些，這是繼續治療的重要驅動力。所以你可能會看到耐受性和功效的平衡在 15 中比在 10 中表現得更好一些。但這些都是相當小的停藥率。如果你看看 AE 的中個位數的停藥率，我認為這真的很棒，比預期的要好。

Thanks, Dan. And Mike, on Trulicity and tirzepatide marketing thoughts?

謝謝，丹。邁克，關於 Trulicity 和 tirzepatide 的營銷思想？

Yes. Thanks for the question. Our focus is going to be growing the class as well as growing our share of market in the class. We'll try to maximize the opportunity for our entire incretin portfolio. I mean, what's most important is not necessarily switches for molecules, existing products but more the new patients that are coming on into the incretin class and winning those new patients. And so I think over time, we'll get a mix between new patient starts and switches from other GLPs. But I think primarily our focus is going to be on really driving tirzepatide wins of new patients coming into the class. And so that will be our approach going forward.

是的。謝謝你的問題。我們的重點將是發展班級以及擴大我們在班級中的市場份額。我們將嘗試最大限度地利用我們整個腸促胰島素產品組合的機會。我的意思是，最重要的不一定是分子、現有產品的轉換，而是更多進入腸促胰島素類並贏得這些新患者的新患者。所以我認為隨著時間的推移，我們將在新患者開始和從其他 GLP 轉換之間得到混合。但我認為主要是我們的重點是真正推動新患者進入課堂的 tirzepatide 勝利。這將是我們前進的方法。

The next caller is Chris Shibutani from Goldman Sachs.

下一位來電者是高盛的 Chris Shibutani。

Two questions, if I may, on tirzepatide and the potential for read-across from Novo's outcome study. That is the next data point, I think, in terms of thinking about the progress of this ultimate opportunity. Can you frame for us what you think would be your expectations? And maybe level-set what you think would be a bar there? I know that you mentioned that you don't believe it's necessarily a gating factor, that would be helpful.

如果可以的話，有兩個問題是關於 tirzepatide 和從 Novo 的結果研究中讀取的可能性。我認為，就這個終極機會的進展而言，這是下一個數據點。您能否為我們制定您認為您的期望的框架？也許水平設置你認為那裡會是一個酒吧？我知道你提到你不相信它一定是一個門控因素，這會有所幫助。

Second question on the post-final NCD for donanemab and the language that CMS used, do you have clarity from perhaps post the final NCD that your current program will adequately address what they believe to be sort of structural requirements for the kinds of studies that need to be conducted in order for CMS to contemplate full reimbursement of Alzheimer's therapy?

關於 donanemab 的最終非傳染性疾病和 CMS 使用的語言的第二個問題，您是否清楚地從最終的非傳染性疾病發佈到您當前的程序將充分解決他們認為需要的研究類型的結構要求為了讓 CMS 考慮全額報銷阿爾茨海默氏症的治療費用？

Thanks, Chris. We'll go to Mike for just his thoughts on outcome studies and the competitive landscape there in obesity and then to Anne for the question on the NCD of donanemab.

謝謝，克里斯。我們將向 Mike 詢問他對肥胖癥結果研究和競爭格局的看法，然後向 Anne 詢問有關 donanemab 的 NCD 的問題。

Yes. Good question. We touched on this a little bit earlier. But I think the we expect the STEP CV study to be successful, given the expected weight loss and what it has expressed. We think that will be important to continue to grow the class and, for some payers, winning access on it. So we hope that the STEP program is successful. We expect it will be. And obviously, we have a very comprehensive Phase III program to demonstrate outcomes for obesity that we also are confident in.

是的。好問題。我們早些時候談到了這一點。但我認為，鑑於預期的體重減輕及其所表達的內容，我們預計 STEP CV 研究會成功。我們認為這對於繼續發展課程很重要，並且對於一些付款人來說，贏得使用它的機會。所以我們希望STEP計劃成功。我們預計會這樣。顯然，我們有一個非常全面的 III 期計劃來展示我們也有信心的肥胖結果。

Thanks, Mike. Anne?

謝謝，邁克。安妮？

Yes. Thanks for the question on donanemab. So as Dan mentioned, our priority will be to advocate for reconsideration with the TB-2 Phase III data. So we do remain confident in donanemab and believe that TB-2 and our overall TRAILBLAZER program have extensive data. And so as we review the requirements in the NCD, we believe our data should be sufficient to meet the high level of evidence criteria set forth by CMS if TB-2 is positive. Obviously, we'll need to review this data with CMS and gain their agreement. So we'll do that very quickly.

是的。感謝您對 donanemab 提出的問題。因此，正如 Dan 所提到的，我們的首要任務是倡導重新考慮 TB-2 III 期數據。因此，我們確實對 donanemab 充滿信心，並相信 TB-2 和我們的整體 TRAILBLAZER 計劃擁有大量數據。因此，當我們審查 NCD 中的要求時，我們認為如果 TB-2 呈陽性，我們的數據應該足以滿足 CMS 提出的高水平證據標準。顯然，我們需要與 CMS 一起審查這些數據並獲得他們的同意。所以我們會很快做到這一點。

Our intention is, as soon as we have that data, to request reconsideration for national coverage. And we believe that having two positive pivotal trials should meet that high level of evidence. As far as CMS, we've engaged with them throughout the process. And so we'll continue to do so moving forward. And there's a number of statements in the NCD that we will seek clarity on to gain additional clarity as we move forward. But yes, we do believe that we should meet that high level of evidence but pending those discussions with CMS.

我們的意圖是，一旦我們有了這些數據，就要求重新考慮全國范圍的覆蓋範圍。而且我們認為，進行兩項積極的關鍵試驗應該能夠滿足如此高水平的證據。就 CMS 而言，我們在整個過程中都與他們合作。因此，我們將繼續這樣做。在 NCD 中有許多聲明，我們將尋求澄清，以便在我們前進的過程中獲得更多的明確性。但是，是的，我們確實相信我們應該滿足如此高水平的證據，但要等待與 CMS 的討論。

The next caller is Robyn Karnauskas from Truist Securities.

下一位來電者是來自 Truist Securities 的 Robyn Karnauskas。

I guess, I'll keep going on the tirzepatide route. So a lot of people asked questions on duration of therapy. Have you talked to payers about once you reach a point where maybe some of your comorbidities are gone and you're on drug, if they're going to be willing to still reimburse therapy?

我想，我會繼續走 tirzepatide 路線。所以很多人問關於治療持續時間的問題。您是否與付款人討論過，一旦您的某些合併症消失並且您正在服藥，他們是否仍願意報銷治療費用？

And then the second question for you is like when you think about this data now that you have it now and it's very robust, what new trials might you think about or new indications, whether it be obesity without comorbidities or other indications might you want to start now that you sort of have this in-house and it's clear?

然後給你的第二個問題是，當你考慮這些數據時，你現在擁有它並且它非常強大，你可能會考慮哪些新試驗或新適應症，無論是沒有合併症的肥胖症還是你可能想要的其他適應症現在開始，你有點在內部有這個，很清楚嗎？

Thanks, Robyn. We'll go to Mike for both of those questions.

謝謝，羅賓。我們將向邁克提出這兩個問題。

Yes. Good questions. And when we were having discussions with payers, they do -- they are excited about the obesity class, if it can demonstrate outcomes. And if they have a patient who is seeing benefits from an antiobesity medication, they actually want to work with us to make sure that those individuals stay on therapy in order to get and maintain the weight loss they have seen.

是的。好問題。當我們與付款人討論時，他們確實 - 他們對肥胖課程感到興奮，如果它可以證明結果的話。如果他們的患者從抗肥胖藥物中受益，他們實際上希望與我們合作，以確保這些人繼續接受治療，以獲得併保持他們所看到的體重減輕。

And so I think there will be opportunities for us to partner with payers to ensure that we can maintain individuals on chronic medications. I think our expectation is that people do need to stay on tirzepatide long term in order to get and maintain the weight benefits. And we will be working with payers to make sure that we can maintain that weight loss, so people can get the outcomes that they need. The second question, remind me, Kevin, what the second question was?

因此，我認為我們將有機會與付款人合作，以確保我們能夠維持個人服用慢性藥物。我認為我們的期望是人們確實需要長期服用 tirzepatide 才能獲得和保持體重益處。我們將與付款人合作，以確保我們能夠保持這種減肥效果，這樣人們就可以獲得他們需要的結果。第二個問題，提醒我，凱文，第二個問題是什麼？

Any new trials or indications as you see this data beyond what we've announced?

當您看到這些數據超出我們宣布的範圍時，是否有任何新的試驗或適應症？

Yes. I mean, nothing that we're going to talk about in today's discussion. Obviously, we'll internalize this data. We will -- this is -- as we said earlier, this is an important therapeutic area for us, massive unmet needs and one that we are looking to play the long-term game on. So when you put those together, we obviously are -- we'll be very thoughtful and aggressive. And if we do feel that there's additional needs for trials on tirzepatide that can provide insights to payers and health care professionals, we'll do those trials.

是的。我的意思是，在今天的討論中我們將不討論任何內容。顯然，我們將內化這些數據。我們將 - 這是 - 正如我們之前所說，這對我們來說是一個重要的治療領域，大量未滿足的需求，我們正在尋求長期遊戲。所以當你把這些放在一起時，我們顯然是——我們會非常周到和積極。如果我們確實認為對 tirzepatide 的試驗有額外的需求，可以為付款人和醫療保健專業人員提供見解，我們將進行這些試驗。

The queue is exhausted. We'll go to Dave for the close.

隊列已用盡。我們將去戴夫為結束。

Okay. Great. Well, thanks for joining today's earnings and tirzepatide call, I guess, and your interest, of course, in the company. It is an exciting moment for all of us.

好的。偉大的。好吧，我想感謝您參加今天的收益和 tirzepatide 電話會議，當然還有您對公司的興趣。這對我們所有人來說都是一個激動人心的時刻。

2022 started in a similar fashion to how we ended 2021 with strong momentum across the business. We remain focused on executing our innovation-based strategy, which, of course, is to bring new medicines to patients and create value for all our stakeholders. With strong commercial execution, complemented by a pipeline of industry-leading opportunities, we believe Lilly continues to be a compelling investment.

2022 年的開始方式與我們在 2021 年結束時的方式類似，整個業務勢頭強勁。我們仍然專注於執行我們基於創新的戰略，這當然是為患者帶來新藥並為我們所有的利益相關者創造價值。憑藉強大的商業執行力，以及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。

So thanks for dialing in today. And please follow up with the IR team if you have questions we have not addressed on the call, and have a great day. Thanks.

所以感謝您今天撥入。如果您有我們在電話會議中未解決的問題，請與 IR 團隊聯繫，祝您度過愉快的一天。謝謝。

Thank you. And ladies and gentlemen, this conference is available for replay beginning after 11:15 Eastern Time today and running through April 28 at midnight. You may access the AT&T replay system at any time by dialing 1 (866) 207-1041, and if you're international, (402) 970-0847, and entering the access code 4726957.

謝謝你。女士們先生們，本次會議可在東部時間今天 11:15 之後開始重播，一直持續到 4 月 28 日午夜。您可以隨時通過撥打 1 (866) 207-1041 訪問 AT&T 重播系統，如果您是國際用戶，請撥打 (402) 970-0847，然後輸入訪問代碼 4726957。

And that does conclude our conference for today. Thank you for your participation and for using AT&T Teleconference Service. You may now disconnect.

這確實結束了我們今天的會議。感謝您的參與和使用 AT&T 電話會議服務。您現在可以斷開連接。