禮來公司 (LLY) 2023 Q1 法說會逐字稿

Ladies and gentlemen, thank you for standing by, and welcome to the Lilly Q1 2023 Earnings Conference Call. (Operator Instructions).

女士們，先生們，感謝你們的支持，歡迎來到禮來 2023 年第一季度收益電話會議。 （操作員說明）。

I would now like to turn the conference over to your host, Joe Fletcher, Senior Vice President of Investor Relations. Please go ahead.

我現在想把會議轉交給你的主持人，投資者關係高級副總裁喬弗萊徹。請繼續。

Good morning, and thank you for joining us for Eli Lilly and Company's Q1 2023 Earnings Call. I'm Joe Fletcher, Senior Vice President of Investor Relations. And 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 at Lilly; Mike Mason, President of Lilly Diabetes; and Patrik Jonsson, President of Lilly Immunology and Lilly USA. We're also joined by Mike Springnether, Kendo Waha and Lauren Zierke of the Investor Relations team.

早上好，感謝您加入禮來公司 2023 年第一季度財報電話會議。我是投資者關係高級副總裁 Joe Fletcher。和我一起參加今天電話會議的還有禮來公司的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；安妮懷特，禮來神經科學總裁；禮來國際總裁 Ilya Yuffa；禮來 Loxo 首席執行官 Jake Van Naarden； Mike Mason，禮來糖尿病總裁；禮來免疫學和禮來美國總裁 Patrik Jonsson。投資者關係團隊的 Mike Springnether、Kendo Waha 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 filings with the Securities and Exchange Commission. The information we provide about our products and pipeline is for the benefit of the investment community. It's 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.

在本次電話會議期間，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存在重大差異的因素的其他信息包含在我們最新的 10-K 表格和隨後提交給美國證券交易委員會的文件中。我們提供的有關我們產品和管道的信息是為了投資界的利益。它不是為了促銷，也不足以規定決策。當我們過渡到準備好的評論時，請注意我們的評論將側重於非 GAAP 財務措施。

Now I'll turn the call over to Dave.

現在我會把電話轉給戴夫。

Thanks, Joe. We're off to a strong start in 2023 with volume-driven revenue growth led by our incretin portfolio, Verzenio and Jardiance. At our Q1 earnings last year, we shared exciting data from SURMOUNT-1, the first of our tirzepatide obesity Phase III trials. Today, we're excited to share the positive top line results for the SURMOUNT-2 Phase III trial for tirzepatide, which examine the safety and efficacy of tirzepatide in chronic weight management in a type 2 diabetes population. SURMOUNT-1 set a new bar for weight loss possible from a pharmacologic agent in non-type 2 diabetes population with obesity or overweight in a Phase III trial. And SURMOUNT-2 does the same in the type 2 diabetes population.

謝謝，喬。我們在 2023 年有了一個良好的開端，我們的腸促胰島素產品組合 Verzenio 和 Jardiance 引領了銷量驅動的收入增長。在我們去年第一季度的收益中，我們分享了來自 SURMOUNT-1 的令人興奮的數據，這是我們 tirzepatide 肥胖 III 期試驗的第一個。今天，我們很高興分享 tirzepatide 的 SURMOUNT-2 III 期試驗的正面頂線結果，該試驗檢查了 tirzepatide 在 2 型糖尿病人群慢性體重管理中的安全性和有效性。在 III 期試驗中，SURMOUNT-1 為肥胖或超重的非 2 型糖尿病人群的藥物減肥可能設定了新的標準。 SURMOUNT-2 在 2 型糖尿病人群中也有同樣的作用。

Before discussing our financial results and pipeline updates, I'd like to also note the actions Lilly announced on March 1 to improve insulin affordability in the United States. We are proud to have led these efforts to make it easier for people to access Lilly insulin, including through the broad implementation of our $35 out-of-pocket cap and a significant reduction in list price for most of our most commonly used insulins. That said, there remains substantial opportunity and need to reduce existing systemic barriers to insulin access and affordability. Bringing affordable insulin to those who need it will require action and engagement by all stakeholders in our health system. But together, we can create real change to improve access and affordability for people who use insulin.

在討論我們的財務業績和管道更新之前，我還想指出禮來公司在 3 月 1 日宣布的提高美國胰島素負擔能力的行動。我們很自豪能夠領導這些努力，使人們更容易獲得 Lilly 胰島素，包括通過廣泛實施我們 35 美元的自付費用上限和大幅降低我們大多數最常用胰島素的標價。也就是說，仍有大量機會和需要減少現有的系統性障礙，以獲取胰島素和負擔得起。為需要的人提供負擔得起的胰島素需要我們衛生系統中所有利益相關者的行動和參與。但是，我們可以一起創造真正的改變，以改善使用胰島素的人的獲取和負擔能力。

Moving to our results. You can see this on Slide 4 that the progress we've made on our strategic deliverables so far this year. Q1 revenue, which includes sales of COVID-19 antibodies -- sorry, excluding sales from COVID-19 antibodies grew 10% or 12% on a constant currency basis, driven by volume growth of 18%. Volume growth in Q1 was underpinned by Mounjaro, which is leading the new product category, which also includes Jaypirca, and we expect it will include additional products in the months and years to come. The new product and growth product classifications represent an evolution from our prior designation of key growth products. We believe that these classifications will help investors see the performance of both our newest products in addition to those with ongoing growth potential.

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交付方面取得的進展。第一季度的收入，包括 COVID-19 抗體的銷售額——抱歉，不包括 COVID-19 抗體的銷售額，按固定匯率計算增長了 10% 或 12%，這是由 18% 的銷量增長推動的。第一季度的銷量增長得到了 Mounjaro 的支持，Mounjaro 在新產品類別中處於領先地位，其中還包括 Jaypirca，我們預計在未來幾個月和幾年中它將包括更多產品。新產品和增長產品分類代表了我們先前指定的關鍵增長產品的演變。我們相信，這些分類將幫助投資者了解我們最新產品以及具有持續增長潛力的產品的表現。

In the first quarter of this year, the new product category contributed $574 million of revenue, and the new product and growth product categories combined to contribute 20 percentage points of volume growth in Q1. These products as well as expecting -- expected upcoming product launches reinforce our belief in the strength of Lilly's growth outlook throughout this decade.

今年第一季度，新品類貢獻了5.74億美元的收入，新品類和增長品類合計貢獻了Q1銷量增長20個百分點。這些產品以及預期——預期即將推出的產品加強了我們對禮來公司在這十年中增長前景實力的信念。

Last Monday, we broke ground at the site of our 2 new manufacturing facilities in Boone County, Indiana. We also announced a further $1.6 billion investment in addition to the previously announced $2.1 billion investment in this project to expand Lilly's manufacturing network for active ingredients and new therapeutic modalities. And our progress continues as planned towards production starting later this year at our Research Triangle Park site in North Carolina.

上週一，我們在印第安納州布恩縣的 2 個新製造工廠破土動工。除了先前宣布的對該項目的 21 億美元投資外，我們還宣布再投資 16 億美元，以擴大禮來（Lilly）的活性成分和新治療模式的製造網絡。我們繼續按計劃在今年晚些時候在北卡羅來納州的 Research Triangle Park 開始生產。

On the business development front, this past week, we entered into agreements to sell the rights of our olanzapine portfolio, including Zyprexa and the rights to Baqsimi. These 2 transactions will enable us to further focus our time and effort on our next-generation medicines. In our pipeline, we've had several important updates since our Q4 earnings call, including label expansion for Verzenio in advanced breast cancer in the U.S.; for mirikizumab approval in Japan and a positive CHMP opinion in the EU as well as the FDA's issuance of a Complete Response Letter in the United States; regulatory submissions in the EU for tirzepatide for chronic weight management and in Japan for lebrikizumab for atopic dermatitis; and a positive Phase III top line readout for SURMOUNT-2, the second global study evaluating tirzepatide for adults living with obesity or overweight, which will enable completion of our rolling submission with the FDA under Fast Track designation.

在業務發展方面，上週，我們簽訂了出售奧氮平產品組合權利的協議，包括 Zyprexa 和 Baqsimi 的權利。這兩項交易將使我們能夠進一步將時間和精力集中在我們的下一代藥物上。在我們的管道中，自第四季度財報電話會議以來，我們已經進行了多項重要更新，包括美國晚期乳腺癌的 Verzenio 標籤擴展； mirikizumab 在日本的批准和歐盟 CHMP 的積極意見以及 FDA 在美國發布的完整回應函；歐盟提交的用於慢性體重管理的 tirzepatide 和日本用於治療特應性皮炎的 lebrikizumab 的監管申請；以及 SURMOUNT-2 的 III 期頂線陽性讀數，SURMOUNT-2 是第二項全球研究，評估 tirzepatide 對患有肥胖或超重的成年人的影響，這將使我們能夠根據快速通道指定完成向 FDA 的滾動提交。

Dan will discuss this further, but we are excited with the top line results of the Phase III SURMOUNT-2 trial. As shared late last year, we received Fast Track designation from the FDA and initiated a rolling submission for tirzepatide in chronic weight management based on the results of the SURMOUNT-1 trial. And we aligned with the FDA that completion of the submission would come following the SURMOUNT-2 readout. We anticipate completing our submission to the FDA in the coming weeks. We believe addressing obesity could make an enormous difference in millions of people's lives, significantly impact public health and reduce health care costs. We are encouraged by this important next step in the journey to redefine obesity care.

Dan 將進一步討論這個問題，但我們對 III 期 SURMOUNT-2 試驗的頂級結果感到興奮。正如去年年底分享的那樣，我們收到了 FDA 的快速通道指定，並根據 SURMOUNT-1 試驗的結果啟動了 tirzepatide 在慢性體重管理中的滾動提交。我們與 FDA 達成一致，即在 SURMOUNT-2 讀數之後完成提交。我們預計在未來幾週內完成向 FDA 的提交。我們相信，解決肥胖問題可以極大地改變數百萬人的生活，顯著影響公共健康並降低醫療保健成本。在重新定義肥胖症護理的旅程中，這一重要的下一步讓我們感到鼓舞。

Finally, this quarter, we distributed $1 billion in dividends and completed $750 million in share repurchases. On Slide 5, you'll see a list of key events since our Q4 earnings call, including several important regulatory, clinical and other updates we are discussing today.

最後，本季度，我們分配了 10 億美元的股息，並完成了 7.5 億美元的股票回購。在幻燈片 5 上，您將看到自我們第四季度財報電話會議以來的一系列重要事件，包括我們今天討論的幾項重要的監管、臨床和其他更新。

Now I'll turn the call over to Anat to review our Q1 results.

現在我將把電話轉給 Anat 來審查我們的第一季度結果。

Thanks, Dave. Slide 6 summarizes financial performance in the first quarter of 2023, and I'll focus my comments on non-GAAP performance. In Q1, revenue declined 11% versus Q1 2022. When excluding revenue from COVID-19 antibodies, revenues increased 10% or 12% on a constant currency basis, highlighting solid momentum for our business despite a substantial headwind from a loss of exclusivity in the United States, which did not yet face meaningful generic competition in the base period.

謝謝，戴夫。幻燈片 6 總結了 2023 年第一季度的財務業績，我將重點關注非 GAAP 業績。第一季度，收入與 2022 年第一季度相比下降了 11%。如果不包括來自 COVID-19 抗體的收入，按固定匯率計算，收入增長了 10% 或 12%，這突顯了我們業務的穩健勢頭，儘管由於失去 COVID-19 抗體的獨家經營權而面臨巨大阻力美國，在基期尚未面臨有意義的仿製藥競爭。

Gross margin as a percent of revenue increased 230 basis points to 78.4% in Q1 2023. The increase in gross margin percent was driven primarily by lower sales of COVID-19 antibodies, partially offset by lower realized prices. Total operating expenses increased 15% this quarter. Marketing, selling and administrative expenses increased 12%, driven by higher marketing and selling expenses associated with recent and upcoming product launches and indications. R&D expenses increased 23%, driven by higher development expenses for late-stage assets.

2023 年第一季度，毛利率佔收入的百分比增長了 230 個基點，達到 78.4%。毛利率增長的主要原因是 COVID-19 抗體的銷售額下降，部分被實現價格下降所抵消。本季度總運營費用增長了 15%。營銷、銷售和管理費用增長了 12%，這是由於與近期和即將推出的產品和適應症相關的營銷和銷售費用增加所致。受後期資產開發費用增加的推動，研發費用增加了 23%。

This quarter, we recognized acquired IP R&D charges of $105 million or $0.10 of EPS. In Q1 2022, acquired IP R&D and development milestone charges totaled $166 million or $0.15 of EPS. Operating income decreased 38% in Q1, driven by lower revenue, primarily due to 0 sales of COVID-19 antibodies this quarter, paired with higher R&D and SG&A expenses. Operating income as a percent of revenue was 23% for the quarter and reflected a negative impact of approximately 150 basis points attributable to acquired IP R&D charges.

本季度，我們確認了 1.05 億美元的收購 IP 研發費用或 0.10 美元的每股收益。 2022 年第一季度，收購的 IP 研發和開發里程碑費用總計 1.66 億美元或每股收益 0.15 美元。第一季度營業收入下降 38%，主要原因是收入下降，這主要是由於本季度 COVID-19 抗體的銷售額為零，加上研發和 SG&A 費用增加。本季度營業收入佔收入的百分比為 23%，反映出約 150 個基點的負面影響歸因於收購的 IP 研發費用。

Our Q1 effective tax rate was 12.8%. This represents an increase of 250 basis points compared to the same period in 2022, driven primarily by the tax impact of the new Puerto Rico tax regime. At the bottom line, we delivered earnings per share of $1.62.

我們第一季度的有效稅率為 12.8%。這比 2022 年同期增加了 250 個基點，這主要是受波多黎各新稅制的稅收影響所推動。最後，我們實現了 1.62 美元的每股收益。

On Slide 7, we quantify the effect of price, rate and volume on revenue growth. This quarter, U.S. revenue declined 14%. As a reminder, COVID-19 antibody revenue in Q1 of 2022 totaled approximately $1.5 billion compared to 0 in Q1 of this year. When excluding revenue from COVID-19 antibodies, U.S. revenue grew 19%, driven by robust volume growth for Mounjaro, Verzenio, Trulicity and Jardiance. We experienced a net price decline of 5% in the U.S. for the quarter, driven primarily by Humalog and Trulicity.

在幻燈片 7 中，我們量化了價格、費率和數量對收入增長的影響。本季度，美國收入下降了 14%。提醒一下，2022 年第一季度的 COVID-19 抗體收入總計約為 15 億美元，而今年第一季度為零。剔除 COVID-19抗體的收入後，美國收入增長了 19%，這得益於 Mounjaro、Verzenio、Trulicity 和 Jardiance 的強勁銷量增長。本季度我們在美國的淨價格下降了 5%，這主要是受 Humalog 和 Trulicity 的推動。

As we move into the second half of 2023, we expect U.S. pricing headwind versus prior year will ease considerably driven by Mounjaro access and saving cards dynamics. Europe continued its steady growth trajectory with revenue in Q1 growing 8% in constant currency, driven primarily by volume growth for Verzenio, Trulicity, Jardiance and Taltz. Volume in Europe increased 13% in Q1. For Japan, Q1 revenue increased 7% in constant currency as the base period impact of generic competition to Cymbalta and Alimta waned, and we continue to see strong robust growth in our newer medicines led by Verzenio and, to a lesser extent, Jardiance.

隨著我們進入 2023 年下半年，我們預計美國定價與上一年相比的逆風將在 Mounjaro 訪問和儲蓄卡動態的推動下大大緩解。歐洲繼續穩步增長，第一季度收入按固定匯率計算增長 8%，主要受 Verzenio、Trulicity、Jardiance 和 Taltz 銷量增長的推動。第一季度歐洲的銷量增長了 13%。對於日本，由於對 Cymbalta 和 Alimta 的仿製藥競爭的基期影響減弱，第一季度收入按固定匯率計算增長了 7%，我們繼續看到以 Verzenio 和 Jardiance 為首的新藥強勁增長。

Moving to China. Revenue declined 1% in constant currency with volume growth of 19% offset by net price declines. Volume growth was driven by Verzenio and, to a lesser extent, increase in shipments of Olumiant. Price declines were largely driven by Humalog, which was added to the volume-based procurement scheme in Q2 of last year. Revenue in the rest of the world decreased 9% in constant currency, driven by the sales of rights to Cialis in Taiwan and Saudi Arabia for $95 million in Q1 of 2022, partially offset by growth in Verzenio, Mounjaro and Jardiance.

搬到中國。按固定匯率計算收入下降 1%，銷量增長 19% 被淨價下降所抵消。銷量增長由 Verzenio 推動，在較小程度上，Olumiant 的出貨量增加。價格下降主要是由 Humalog 推動的，它在去年第二季度被添加到基於批量的採購計劃中。受 2022 年第一季度以 9500 萬美元在台灣和沙特阿拉伯出售 Cialis 權利的推動，世界其他地區的收入按固定匯率計算下降了 9%，部分被 Verzenio、Mounjaro 和 Jardiance 的增長所抵消。

Slide 8 shows the contribution to worldwide volume growth by product category. As Dave mentioned earlier, we have evolved a prior product categorization from key growth products, which included 10 key products launched since 2014 to now focus on 2 categories, the first called new product and the second called growth product. The new product categories led by Mounjaro and also includes Jaypirca, and we expect to expand to include new products in the coming months and years. The growth product category is made up of select products that have been in the market for several years with continued exclusivity.

幻燈片 8 按產品類別顯示了對全球銷量增長的貢獻。正如 Dave 之前提到的，我們已經從關鍵增長產品發展了先前的產品分類，其中包括自 2014 年以來推出的 10 種關鍵產品，現在專注於 2 個類別，第一個稱為新產品，第二個稱為增長產品。由 Mounjaro 領導的新產品類別還包括 Jaypirca，我們希望在未來幾個月和幾年內擴展到包括新產品。成長型產品類別由已在市場上銷售數年且持續獨占的精選產品組成。

As you can see, the new and growth product categories contributed over 20 percentage points of volume growth for the quarter, which was largely offset by the previously mentioned decline in COVID-19 antibody revenue. While the lack of revenue from COVID-19 antibody will be a headwind to growth throughout the year, the most substantial impact was in Q1. As I mentioned earlier, in Q1 2022, we realized approximately $1.5 billion of revenue from COVID-19 antibodies, representing 75% of the $2 billion sold in the full year 2022.

正如您所看到的，新產品和增長產品類別貢獻了本季度超過 20 個百分點的銷量增長，這在很大程度上被前面提到的 COVID-19 抗體收入下降所抵消。雖然 COVID-19 抗體收入不足將阻礙全年增長，但影響最大的是第一季度。正如我之前提到的，在 2022 年第一季度，我們從 COVID-19 抗體中實現了約 15 億美元的收入，佔 2022 年全年銷售額 20 億美元的 75%。

Slide 9 provides additional perspective on the trends and specific highlights across our product categories. I'll speak more about Mounjaro shortly, but first, let me highlight the continued outstanding performance of Verzenio, which saw worldwide sales growth of 60% in Q1 as the long-term monarchE follow-up data shared at the San Antonio Breast Cancer Symposium last December and the recently expanded label support continued uptake in adjuvant breast cancer. Verzenio is now the standard of care in its Category 1 NCCN listed for high-risk adjuvant breast cancer.

幻燈片 9 提供了有關我們產品類別的趨勢和特定亮點的更多視角。稍後我將詳細介紹 Mounjaro，但首先，讓我強調一下 Verzenio 持續出色的表現，作為在聖安東尼奧乳腺癌研討會上分享的長期 monarchE 後續數據，第一季度全球銷售額增長了 60%去年 12 月和最近擴大的標籤支持在輔助乳腺癌中繼續攝取。 Verzenio 現在是其第 1 類 NCCN 中列出的用於高風險輔助乳腺癌的護理標準。

Jardiance also continued its outstanding performance with worldwide sales growth of 38% for the quarter. In Q1, we were pleased to announce that based on the results of the Phase III DINAMO trial, the FDA accepted the supplemental New Drug Application for Jardiance for children 10 years and older with type 2 diabetes. And lastly, we continue to be encouraged by the strength of Trulicity's performance in a growing and dynamic incretin market. Worldwide sales of Trulicity grew 14% in Q1, anchored by the product's robust efficacy and safety profile, coupled with the convenient and easy-to-use device. Looking more holistically at Trulicity and Mounjaro together, U.S. revenue for these 2 products grew 59% in Q1 2023 versus Q1 2022.

Jardiance 也繼續其出色的表現，本季度全球銷售額增長了 38%。在第一季度，我們很高興地宣布，根據 DINAMO III 期試驗的結果，FDA 接受了針對 10 歲及以上患有 2 型糖尿病的兒童的 Jardiance 補充新藥申請。最後，我們繼續對 Trulicity 在不斷增長和充滿活力的腸促胰島素市場中的表現感到鼓舞。 Trulicity 的全球銷售額在第一季度增長了 14%，這得益於該產品強大的功效和安全性，以及方便易用的設備。更全面地看一下 Trulicity 和 Mounjaro，這兩種產品在美國的收入在 2023 年第一季度比 2022 年第一季度增長了 59%。

Moving to Slide 10. Let me share some commentary and context on Mounjaro's performance for the quarter. We are pleased with the positive momentum over the course of Q1 as it means more patients with type 2 diabetes are realizing the substantial benefits of treatment with Mounjaro. While the trajectory of prescription growth shifted following our actions in Q4 to reinforce the intended use of Mounjaro savings program by type 2 diabetes patients, we have continued to see a positive overall trend. Our focus is on driving new-to-brand growth while continuing to expand access.

轉到幻燈片 10。讓我分享一些關於 Mounjaro 本季度業績的評論和背景。我們對第一季度的積極勢頭感到滿意，因為這意味著更多的 2 型糖尿病患者正在意識到 Mounjaro 治療的巨大益處。雖然我們在第四季度採取行動以加強 2 型糖尿病患者對 Mounjaro 儲蓄計劃的預期使用，但處方藥增長的軌跡發生了變化，但我們繼續看到積極的總體趨勢。我們的重點是在繼續擴大訪問範圍的同時推動新品牌增長。

In Q1, we initiated our first Mounjaro direct-to-consumer TV campaign, and we continue to steadily build access from Mounjaro for type 2 diabetes. As of April 1, access stood at just under 60% for patients with type 2 diabetes across commercial and Part D. We estimate that the percentage of paid scripts for Mounjaro in Q1 was just over 55%, up from approximately 40% in Q4 2022.

在第一季度，我們發起了第一個 Mounjaro 直接面向消費者的電視活動，我們繼續穩步建立從 Mounjaro 獲取 2 型糖尿病的途徑。截至 4 月 1 日，2 型糖尿病患者在商業廣告和 D 部分的訪問率略低於 60%。我們估計，Mounjaro 在第一季度的付費劇本百分比略高於 55%，高於 2022 年第四季度的約 40% .

As a reminder, we define paid scripts as those prescription outside the $25 non-covered co-pay cards but inclusive of the $25 covered co-pay card. Looking forward to Q2 and the rest of the year, we expect continued improvement in access in the proportion of paid scripts and in new-to-brand prescription.

提醒一下，我們將付費腳本定義為 25 美元非承保自付卡之外但包括 25 美元承保自付卡的那些處方。展望第二季度和今年剩餘時間，我們預計付費劇本和新品牌處方的比例會繼續提高。

On Slide 11, we provide an update on capital allocation. In Q1 2023, we invested $2.7 billion in our future growth through a combination of R&D expenditures, business development outlays and capital investments. In addition, we returned just over $1 billion to shareholders in dividends and repurchased $700 million in stock.

在幻燈片 11 中，我們提供了資本配置的最新信息。 2023 年第一季度，我們通過研發支出、業務發展支出和資本投資相結合，為未來增長投資了 27 億美元。此外，我們向股東返還了超過 10 億美元的股息，並回購了 7 億美元的股票。

Slide 12 represents our updated 2023 financial guidance. Starting with revenue, we are increasing the revenue guidance range by $900 million to now be in the range of $31.2 billion to $31.7 billion. Since announcing our 2023 financial guidance in December, the U.S. dollar has weakened against most major currencies. We have updated our full year revenue outlook based on recent spot rates. This FX update is driving approximately $650 million of the $900 million increase in our revenue guidance. The remainder of the increase is attributable to underlying business performance. Our guidance for gross margin as a percent of revenue remains unchanged.

幻燈片 12 代表我們更新的 2023 年財務指南。從收入開始，我們將收入指導範圍增加了 9 億美元，目前在 312 億美元至 317 億美元之間。自去年 12 月宣布 2023 年財務指引以來，美元兌大多數主要貨幣走弱。我們根據最近的即期匯率更新了全年收入展望。在我們的收入指引增加 9 億美元中，此次 FX 更新推動了約 6.5 億美元。其餘增長歸因於基礎業務績效。我們對毛利率佔收入百分比的指引保持不變。

In terms of operating expenses, we are increasing the range of marketing, selling and administrative costs by $100 million to reflect our updated exchange rate assumptions. This results in an updated range of $7 billion to $7.2 billion. We are also increasing the range for research and development expenses by $100 million, driven by updated exchange rate assumptions and investments in our late-stage portfolio. This results in an updated R&D range of $8.3 billion to $8.5 billion.

在運營費用方面，我們將營銷、銷售和管理成本的範圍增加了 1 億美元，以反映我們更新後的匯率假設。這導致更新後的範圍為 70 億美元至 72 億美元。在更新的匯率假設和對我們後期投資組合的投資的推動下，我們還將研發費用的範圍增加了 1 億美元。這導致更新後的研發範圍為 83 億美元至 85 億美元。

We have incorporated IP R&D charges that have been incurred or realized as of the date of earnings, which totaled $105 million. Consistent with prior quarters, we have not included any IP R&D charges associated with potential or pending business development transactions. Additionally, the recently announced agreements to sell the right of our olanzapine portfolio and of Baqsimi have now been included in guidance. Each transactions will be factored into our financial guidance after it closes. Other income and expenses and tax rate guidance remain unchanged.

我們納入了截至收益之日已經發生或實現的知識產權研發費用，總計 1.05 億美元。與前幾個季度一致，我們沒有計入與潛在或未決業務開發交易相關的任何知識產權研發費用。此外，最近宣布的出售奧氮平產品組合和 Baqsimi 權利的協議現已包含在指南中。每筆交易都將在交易結束後納入我們的財務指導。其他收入和支出以及稅率指引保持不變。

Based on these changes, we are raising our full year reported EPS guidance to now be in the range of $8.18 to $8.38 per share and raising our non-GAAP EPS guidance to be in the range of $8.65 to $8.85.

基於這些變化，我們將全年報告的每股收益指引上調至每股 8.18 美元至 8.38 美元，並將我們的非 GAAP 每股收益指引上調至 8.65 美元至 8.85 美元。

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

現在我將把電話轉給 Dan，強調我們在研發方面的進展。

Thanks, Anat. Let me start with today's exciting announcement, the positive results for tirzepatide in the SURMOUNT-2 Phase III study. Tirzepatide met the co-primary study endpoints and also hit on all prespecified key secondary endpoints. Participants with obesity or overweight and with type 2 diabetes achieved up to 16% weight loss at 72 weeks, which translates to a mean weight loss of 34 pounds.

謝謝，阿納特。讓我從今天激動人心的公告開始，即 SURMOUNT-2 III 期研究中 tirzepatide 的積極結果。 Tirzepatide 達到了共同主要研究終點，也達到了所有預先指定的關鍵次要終點。患有肥胖或超重以及患有 2 型糖尿病的參與者在 72 週時體重減輕了 16%，這意味著平均體重減輕了 34 磅。

Additionally, 86% of people taking 15-milligram tirzepatide achieved at least 5% body rate reduction. This was in line with our expectations based on our SURPASS-3 data in a similar population. With this SURMOUNT-2 data, we now have 2 positive Phase III trials for tirzepatide in obesity, 1 in patients without type 2 diabetes and 1 in patients with type 2 diabetes. We now look forward to completing our rolling submission to the FDA in the coming weeks.

此外，服用 15 毫克 tirzepatide 的人中有 86% 的人身體率至少降低了 5%。這符合我們基於我們在類似人群中的 SURPASS-3 數據的預期。有了這個 SURMOUNT-2 數據，我們現在有 2 項關於 tirzepatide 治療肥胖症的陽性 III 期試驗，1 項針對非 2 型糖尿病患者，1 項針對 2 型糖尿病患者。我們現在期待在未來幾週內完成向 FDA 的滾動提交。

I'll cover the SURMOUNT-2 results in more detail, but first, let me spend a few minutes providing an overview of the SURMOUNT Phase III program. The SURMOUNT program has enrolled more than 5,000 people with obesity or overweight across 8 studies.

我將更詳細地介紹 SURMOUNT-2 結果，但首先，讓我花幾分鐘時間概述一下 SURMOUNT III 期計劃。 SURMOUNT 計劃在 8 項研究中招募了 5,000 多名肥胖或超重患者。

On Slide 13, you can see key trial design elements for the core SURMOUNT-1 to 4 studies as well as the more recently announced SURMOUNT-MMO and SURMOUNT-5 studies. Five of the 6 studies compare efficacy and safety of tirzepatide to placebo as an adjunct to reduced calorie diet and increased physical activity, while the most recently posted trial, SURMOUNT-5 compares tirzepatide to 2.4-milligram semaglutide.

在幻燈片 13 上，您可以看到核心 SURMOUNT-1 至 4 研究以及最近公佈的 SURMOUNT-MMO 和 SURMOUNT-5 研究的關鍵試驗設計元素。 6 項研究中有 5 項比較了 tirzepatide 與安慰劑作為減少卡路里飲食和增加身體活動的輔助手段的療效和安全性，而最近發布的試驗 SURMOUNT-5 將 tirzepatide 與 2.4 毫克 semaglutide 進行了比較。

As a reminder, SURMOUNT-1 was designed to evaluate treatment with tirzepatide compared to placebo for people without type 2 diabetes with obesity or overweight with at least 1 comorbidity. And it delivered up to 22.5% mean body weight reduction. SURMOUNT-2, which we're reporting today, evaluated treatment with tirzepatide compared to placebo for people with obesity or overweight and type 2 diabetes. SURMOUNT-3 will provide data on maximizing weight loss following an intensive lifestyle program and SURMOUNT-4 evaluates maintaining weight loss.

提醒一下，SURMOUNT-1 旨在評估 tirzepatide 與安慰劑相比對非 2 型糖尿病伴肥胖或超重且至少有 1 種合併症的患者的治療效果。它的平均體重減輕了 22.5%。我們今天報導的 SURMOUNT-2 評估了替西帕肽與安慰劑相比對肥胖或超重和 2 型糖尿病患者的治療效果。 SURMOUNT-3 將提供強化生活方式計劃後最大程度減輕體重的數據，而 SURMOUNT-4 將評估維持體重減輕情況。

SURMOUNT-5 is an open-label trial that will enroll 700 adults who have obesity or overweight with weight-related comorbidities without type 2 diabetes and will compare the efficacy and safety of tirzepatide to semaglutide 2.4-milligrams. Finally, SURMOUNT-MMO is our Phase III morbidity and mortality and obesity study to evaluate improved outcomes for patients with obesity. We expect the next 2 studies, SURMOUNT-3 and SURMOUNT-4 to read out later this year, while SURMOUNT-5 is anticipated to complete in the first half of 2025. SURMOUNT-MMO, as an outcome study, will take several more years to complete.

SURMOUNT-5 是一項開放標籤試驗，將招募 700 名患有肥胖或超重並伴有體重相關合併症但未患 2 型糖尿病的成年人，並將比較替西帕肽與 semaglutide 2.4 毫克的療效和安全性。最後，SURMOUNT-MMO 是我們的 III 期發病率和死亡率以及肥胖研究，旨在評估肥胖患者的改善結果。我們預計接下來的兩項研究 SURMOUNT-3 和 SURMOUNT-4 將在今年晚些時候宣讀，而 SURMOUNT-5 預計將在 2025 年上半年完成。SURMOUNT-MMO 作為一項成果研究，將需要幾年的時間去完成。

On Slide 14, you can see the first co-primary endpoint in the SURMOUNT-2 study where tirzepatide 15-milligram delivered 15.7% mean body weight reduction in adults with type 2 diabetes with obesity or overweight. With a baseline weight across the study of 222 pounds, tirzepatide treatment led to a mean body weight reduction of 34 pounds on the 15-milligram arm of the study. We're also very pleased to see how well the 10-milligram tirzepatide performed with a 13.4% mean body weight reduction, also at 72 weeks for the efficacy estimand. Results for the treatment regimen estimand were similar to the efficacy estimand and are detailed in this morning's SURMOUNT-2 press release.

在幻燈片 14 上，您可以看到 SURMOUNT-2 研究中的第一個共同主要終點，其中 15 毫克 tirzepatide 使患有肥胖或超重的 2 型糖尿病成人的平均體重減輕了 15.7%。整個研究的基線體重為 222 磅，tirzepatide 治療導致該研究的 15 毫克組的平均體重減輕了 34 磅。我們也很高興地看到 10 毫克 tirzepatide 的表現如何，平均體重減輕了 13.4%，在 72 週時的療效估計也是如此。治療方案估計結果與療效估計結果相似，在今天上午的 SURMOUNT-2 新聞稿中有詳細說明。

Moving to Slide 15. Tirzepatide achieved the second co-primary endpoint of achieving at least 5% body weight reduction. SURMOUNT-2 showed up to 86.4% of patients achieved this level of weight reduction at 72 weeks, again, using the efficacy estimand. This is compared to 30.6% of patients on placebo as an adjunct to diet and exercise. Furthermore, over half of all participants in the 15-milligram treatment arm achieved at least 15% weight loss. It has been previously observed in incretin obesity trials that weight loss in a type 2 diabetes population is less than weight loss seen in a non-type 2 diabetes population, a finding consistent with the results we've now reported from the SURMOUNT-1 and SURMOUNT-2 trials. The average weight reductions reported in the SURMOUNT-2 trial in patients with type 2 diabetes range from 7% to 8% less than those seen in SURMOUNT-1, which was an exclusively non-type 2 diabetes population.

轉到幻燈片 15。Tirzepatide 實現了第二個聯合主要終點，即至少減輕 5% 的體重。 SURMOUNT-2 顯示高達 86.4% 的患者在 72 週時達到了這一體重減輕水平，再次使用療效估計。相比之下，30.6% 的患者服用安慰劑作為飲食和運動的輔助手段。此外，超過一半的 15 毫克治療組參與者的體重至少減輕了 15%。之前在腸促胰島素肥胖試驗中觀察到，2 型糖尿病人群的體重減輕低於非 2 型糖尿病人群的體重減輕，這一發現與我們現在從 SURMOUNT-1 和SURMOUNT-2 試驗。在 SURMOUNT-2 試驗中報告的 2 型糖尿病患者的平均體重減輕範圍比 SURMOUNT-1 中觀察到的低 7% 到 8%，SURMOUNT-1 是完全非 2 型糖尿病人群。

There are a number of potential mechanisms that may explain this effect, including the weight gain-promoting effects of some classes of anti-hyperglycemic medications used in the treatment of type 2 diabetes, improving insulin sensitivity with tirzepatide treatment, gender differences between 2 populations and diminished caloric loss effects of glucosuria. These differences manifested as we expected, and the SURMOUNT-2 top line results represent the most robust weight loss seen in a Phase III pharmacological clinical trial consisting entirely of type 2 diabetes patients with obesity or overweight, and we are highly pleased with these results.

有許多潛在的機制可以解釋這種影響，包括用於治療 2 型糖尿病的某些類別的抗高血糖藥物的體重增加促進作用、使用替西帕肽治療改善胰島素敏感性、2 種人群之間的性別差異和減少糖尿的熱量損失效應。這些差異正如我們預期的那樣表現出來，SURMOUNT-2 的頂線結果代表了完全由肥胖或超重的 2 型糖尿病患者組成的 III 期藥理學臨床試驗中觀察到的最強勁的減肥效果，我們對這些結果非常滿意。

Moving to Slide 16. You can see the safety profile from the SURMOUNT-2 study. Tirzepatide was well tolerated in the study participants with the overall safety and tolerability profile similar to incretin-based therapies approved for treatment of obesity. As in SURMOUNT-1 and the SURPASS program, the most commonly reported adverse events were GI-related, were generally mild to moderate in severity and usually occurred through dose escalation. Treatment discontinuation rates due to adverse events were 3.8% and 7.4% for the 10- and 15-milligram tirzepatide treatment arms, respectively, compared to 3.8% for placebo. The overall treatment discontinuation rates were 9.3% and 13.8% in the 10- and 15-milligram tirzepatide treatment arms compared to 14.9% for placebo.

轉到幻燈片 16。您可以看到 SURMOUNT-2 研究的安全概況。 Tirzepatide 在研究參與者中的耐受性良好，其總體安全性和耐受性與批准用於治療肥胖症的基於腸降血糖素的療法相似。與 SURMOUNT-1 和 SURPASS 計劃一樣，最常報告的不良事件與 GI 相關，嚴重程度通常為輕度至中度，通常通過劑量增加發生。 10 毫克和 15 毫克 tirzepatide 治療組因不良事件導致的治療中止率分別為 3.8% 和 7.4%，而安慰劑組為 3.8%。 10 毫克和 15 毫克 tirzepatide 治療組的總體治療中斷率分別為 9.3% 和 13.8%，而安慰劑組為 14.9%。

We look forward to sharing more data from SURMOUNT-2 at the American Diabetes Association meeting in June and to submitting the results for publication in a peer-reviewed journal. Obesity is a widespread and chronic disease in need of more effective treatment options. The FDA Fast Track designation that tirzepatide received for obesity reflects the seriousness of the condition and the substantial unmet medical need. With impressive trial results now in hand for SURMOUNT-2 and SURMOUNT-1 studies, we look forward to completing our rolling submission to the FDA for tirzepatide for the treatment of adults with obesity or overweight with weight-related comorbidities in the coming weeks.

我們期待在 6 月的美國糖尿病協會會議上分享更多來自 SURMOUNT-2 的數據，並提交結果以在同行評審的期刊上發表。肥胖是一種廣泛存在的慢性疾病，需要更有效的治療方案。 tirzepatide 因肥胖而獲得的 FDA 快速通道指定反映了病情的嚴重性和未滿足的醫療需求。憑藉 SURMOUNT-2 和 SURMOUNT-1 研究的令人印象深刻的試驗結果，我們期待在未來幾週內完成向 FDA 提交替西帕肽用於治療患有肥胖或超重並伴有體重相關合併症的成年人的滾動提交。

With respect to regulatory action in Europe, as Dave mentioned, we have already completed our submission to the EMA for chronic weight management indication. The EMA submission was initiated based on the results from the SURPASS trial program in type 2 diabetes and the SURMOUNT-1 Phase III trial in obesity. We expect to have a European Commission decision in the first half of 2024. In addition to all the work on tirzepatide for obesity, we also disclosed earlier this month on clinicaltrials.gov the initiation of a bioequivalent study to compare the pharmacokinetics of tirzepatide administered using the existing auto-injector device and a new test device. We expect to work on tirzepatide and other injectable incretins for a long time. And we intend to explore different presentations for these medicines to meet our goal of bringing the benefits to as many patients as possible as quickly as possible.

關於歐洲的監管行動，正如 Dave 提到的，我們已經完成了向 EMA 提交的慢性體重管理適應症。 EMA 提交是根據 2 型糖尿病 SURPASS 試驗計劃和肥胖症 SURMOUNT-1 III 期試驗的結果啟動的。我們預計將在 2024 年上半年做出歐盟委員會的決定。除了所有針對肥胖症的 tirzepatide 的工作外，我們還在本月早些時候在 clinicaltrials.gov 上披露了一項生物等效性研究的啟動，以比較使用 tirzepatide 給藥的藥代動力學現有的自動注射器裝置和新的測試裝置。我們期待長期致力於 tirzepatide 和其他注射用腸促胰島素的研究。我們打算探索這些藥物的不同表現形式，以實現我們的目標，即盡快讓盡可能多的患者受益。

Moving on from tirzepatide to the rest of the portfolio. Slide 17 shows select pipeline opportunities as of April 24, and Slide 18 shows potential key events for the year. There have been several important developments since our last earnings call, and I'll cover these by therapeutic area. Continuing within diabetes and metabolic disease.

從 tirzepatide 轉向其他產品組合。幻燈片 17 顯示了截至 4 月 24 日的精選管道機會，幻燈片 18 顯示了今年潛在的關鍵事件。自我們上次財報電話會議以來，出現了一些重要的進展，我將按治療領域進行介紹。繼續研究糖尿病和代謝性疾病。

Earlier this month, we began recruiting for the first Phase III clinical trial for orforglipron, our oral GLP-1 non-peptide agonist. This ACHIEVE-4 trial is an open-label study of orforglipron compared with insulin glargine in adults with type 2 diabetes and obesity or overweight at increased risk for cardiovascular events.

本月早些時候，我們開始招募口服 GLP-1 非肽激動劑 orforglipron 的第一個 III 期臨床試驗。這項 ACHIEVE-4 試驗是一項開放標籤研究，在患有 2 型糖尿病和肥胖或超重的心血管事件風險增加的成人中比較奧福格列酮與甘精胰島素。

This is the first in what will be a broader series of studies for orforglipron. It is the largest and longest trial in the program, which is why we chose to initiate this trial first. Enrollment is now underway and we expect patient dosing to recur shortly, after which orforglipron will be placed with our Phase III assets on the summary slide. You'll also see we have advanced our Relaxin long-acting molecule to Phase II development for treatment of heart failure.

這是針對 orforglipron 的更廣泛系列研究中的第一項。這是該計劃中規模最大、時間最長的試驗，這也是我們選擇首先啟動該試驗的原因。招募工作正在進行中，我們預計很快就會重新開始對患者進行給藥，之後 orforglipron 將與我們的 III 期資產一起放在摘要幻燈片上。您還會看到我們已將 Relaxin 長效分子推進到用於治療心力衰竭的 II 期開發。

Shifting to immunology. It was a quarter of mixed progress for mirikizumab, our IL-23 P19 inhibitor. We were pleased with the approval in late March in Japan for mirikizumab under the brand name Omvoh for adults with moderately to severely active ulcerative colitis. A few days later, we were similarly pleased with the positive CHMP opinion from the EMA. However, regarding mirikizumab's regulatory path in the United States, we announced earlier this month that we received a Complete Response Letter from the FDA. The letter did not cite any concerns regarding the safety or efficacy profile of mirikizumab but focused exclusively on certain aspects related to the proposed commercial manufacturing of mirikizumab.

轉向免疫學。我們的 IL-23 P19 抑製劑 mirikizumab 取得了四分之一的進展。我們很高興 3 月下旬在日本批准了品牌名為 Omvoh 的 mirikizumab 用於患有中度至重度活動性潰瘍性結腸炎的成人。幾天后，我們同樣對 EMA 對 CHMP 的積極意見感到高興。然而，關於mirikizumab在美國的監管路徑，我們本月早些時候宣布我們收到了來自FDA的完整回應函。這封信沒有提及任何關於米利珠單抗安全性或有效性概況的擔憂，而是專注於與擬議的米利珠單抗商業化生產相關的某些方面。

We remain confident mirikizumab's Phase III data and its potential to help people with ulcerative colitis. We look forward to working with the FDA to address the manufacturing questions in order to achieve our goal of bringing mirikizumab to patients in the U.S.

我們對 mirikizumab 的 III 期數據及其幫助潰瘍性結腸炎患者的潛力充滿信心。我們期待與 FDA 合作解決製造問題，以實現我們將 mirikizumab 帶給美國患者的目標。

Also in our late phase immunology portfolio, we completed the regulatory submission in Japan for lebrikizumab for patients with atopic dermatitis. Moving earlier in our immunology pipeline, during last month's American Academy of Dermatology meeting, we shared data from the single-dose Phase II trial for eltrecabart, our CXCR1/2 antibody in patients with hidradenitis suppurativa. The data showed good tolerability and clear separation between eltrecabart and placebo, along with a reduction in abscesses and nodules, reflecting reduced disease activity.

同樣在我們的晚期免疫學產品組合中，我們在日本完成了針對特應性皮炎患者的 lebrikizumab 的監管提交。在我們的免疫學管道中，在上個月的美國皮膚病學會會議上，我們更早地分享了 eltrecabart 單劑量 II 期試驗的數據，我們的 CXCR1/2 抗體用於化膿性汗腺炎患者。數據顯示 eltrecabart 和安慰劑之間具有良好的耐受性和明顯的分離，以及膿腫和結節的減少，反映出疾病活動度降低。

Lastly, in immunology, we've removed respegaldesleukin from our pipeline. In February, following the top line data announcement from the Phase II study in systemic lupus erythematosus, we informed our partner, Nektar Therapeutics that we do not intend to advance the asset into Phase III development.

最後，在免疫學方面，我們已經從我們的產品線中移除了respegaldesleukin。 2 月，在系統性紅斑狼瘡 II 期研究的頂級數據公佈後，我們通知我們的合作夥伴 Nektar Therapeutics，我們不打算將該資產推進到 III 期開發。

Moving on to neuroscience. Last month, we announced that our last active solanezumab trial, the antiamyloid in asymptomatic Alzheimer's disease study or A4 study did not meet its primary or secondary endpoints. The A4 study was conducted through an innovative public-private partnership, and we were thankful for the time and effort of the clinical study staff, participants and study partners. This study formally concludes our clinical development of solanezumab. The A4 results, while disappointing, were not a surprise, given the advancements in our understanding of Alzheimer's disease since the study initiated almost 10 years ago.

繼續神經科學。上個月，我們宣布我們最後一項有效的 solanezumab 試驗，無症狀阿爾茨海默病研究或 A4 研究中的抗澱粉樣蛋白未達到其主要或次要終點。 A4 研究是通過創新的公私合作夥伴關係進行的，我們感謝臨床研究人員、參與者和研究合作夥伴所付出的時間和努力。這項研究正式結束了我們對 solanezumab 的臨床開發。 A4 的結果雖然令人失望，但並不令人意外，因為自該研究近 10 年前開始以來，我們對阿爾茨海默氏病的理解有了進步。

Solanezumab only targets soluble amyloid beta and does not clear plaque. Donanemab and remternetug, on the other hand, have been specifically designed to bind to and clear amyloid plaque, and we now understand that substantial plaque clearance is required in order for anti-amyloid drugs to show clinical efficacy. Accordingly, we were pleased to share new data for donanemab and remternetug during the International Conference on Alzheimer's and Parkinson's disease in late March. For donanemab, we shared data from our TRAILBLAZER-EXT, a Phase II long-term follow-on study of TRAILBLAZER-ALZ.

Solanezumab 僅靶向可溶性澱粉樣蛋白 β，不清除斑塊。另一方面，Donanemab 和 remternetug 專門設計用於結合和清除澱粉樣蛋白斑塊，我們現在了解到，為了使抗澱粉樣蛋白藥物顯示臨床療效，需要大量清除斑塊。因此，我們很高興在 3 月底的阿爾茨海默病和帕金森病國際會議期間分享 donanemab 和 remternetug 的新數據。對於 donanemab，我們共享了來自 TRAILBLAZER-EXT 的數據，TRAILBLAZER-EXT 是 TRAILBLAZER-ALZ 的 II 期長期後續研究。

While study limitations include a relatively small number of patients, the data showed encouraging trends and the longer-term effects on amyloid and tau levels and clinical progression. We also disclosed the trial design and objective for TRAILBLAZER-ALZ 6, a Phase IIIb study to expand the science and understanding of ARIA in relationship to amyloid lowering through imaging and blood-based biomarkers in different dosing paradigms. This study will leverage enhanced MRI sequences as well as blood-based biomarkers and other patient characteristics that may predict ARIA. And we'll investigate the effect of different dosing regimens on the frequency and severity of ARIA.

雖然研究局限性包括相對較少的患者，但數據顯示出令人鼓舞的趨勢以及對澱粉樣蛋白和 tau 水平和臨床進展的長期影響。我們還披露了 TRAILBLAZER-ALZ 6 的試驗設計和目標，這是一項 IIIb 期研究，旨在通過不同劑量範例中的成像和基於血液的生物標誌物，擴大對 ARIA 與澱粉樣蛋白降低相關的科學和理解。這項研究將利用增強的 MRI 序列以及基於血液的生物標誌物和其他可能預測 ARIA 的患者特徵。我們將研究不同給藥方案對 ARIA 頻率和嚴重程度的影響。

Of course, we expect the next key milestone for donanemab will be later this quarter when we obtain the results for our confirmatory Phase III TRAILBLAZER-ALZ 2 trial. We look forward to sharing these results and to advancing the regulatory process for donanemab assuming positive data from this trial. This quarter, we also shared the first clinical data from remternetug from a Phase I multiple ascending dose study, which highlighted the potential speed and depth of amyloid plaque lowering in patients with Alzheimer's disease. These data on amyloid clearance, safety and tolerability supported our decision to move this asset into Phase III, and we look forward to sharing further updates as the program progresses.

當然，我們預計 donanemab 的下一個關鍵里程碑將在本季度晚些時候獲得我們確認的 III 期 TRAILBLAZER-ALZ 2 試驗的結果。我們期待著分享這些結果並推進 donanemab 的監管流程，假設該試驗的數據是積極的。本季度，我們還分享了來自 I 期多次遞增劑量研究的 remternetug 的第一份臨床數據，該數據強調了阿爾茨海默病患者澱粉樣蛋白斑塊降低的潛在速度和深度。這些關於澱粉樣蛋白清除率、安全性和耐受性的數據支持我們將該資產轉移到 III 期的決定，我們期待隨著項目的進展分享進一步的更新。

You'll also notice we have a number of developments in our early-stage neuroscience portfolio with a Phase II entry for our GBA1 Gene Therapy asset in the Gaucher disease type 1 indication along with 2 Phase I pain asset entries and 1 Phase II pain asset discontinuation.

您還會注意到，我們在早期神經科學產品組合中取得了多項進展，其中有一項針對戈謝病 1 型適應症的 GBA1 基因治療資產的 II 期條目，以及 2 項 I 期疼痛資產條目和 1 項 II 期疼痛資產停藥。

Shifting now to oncology. Just yesterday, Jaypirca received a positive opinion from the CHMP for the treatment of relapsed or refractory mantle cell lymphoma. In early March, the FDA approved an expanded indication for Verzenio for the adjuvant treatment of adult patients with HR-positive HER2-negative node positive early breast cancer at high risk of recurrence. High-risk patients can now be more easily identified with the removal of the Ki-67 score requirement for patient selection.

現在轉向腫瘤學。就在昨天，Jaypirca 收到了 CHMP 對治療復發或難治性套細胞淋巴瘤的肯定意見。 3 月初，FDA 批准了 Verzenio 的擴展適應症，用於輔助治療 HR 陽性 HER2 陰性淋巴結陽性且複發風險高的成年早期乳腺癌患者。現在可以更輕鬆地識別高危患者，因為患者選擇時不再需要 Ki-67 評分。

Moving earlier in our oncology pipeline. We presented data from our Phase I study of our KRASG12C inhibitor as part of the AACR meeting last week. These data show promising efficacy and the potential for a differentiated safety profile in combination with pembrolizumab. We're working on finalizing dose selection for our drug in combination with pembrolizumab. And at AACR, we also showed data from CYCLONE 1, a single-arm unblinded study, which was the first to investigate Verzenio in prostate cancer. This early study informed the design of our CYCLONE 2 adaptive Phase II/III trial, which last year cleared our preset threshold to advance to Phase III and for which we expect to read out as soon as late this year. Q1 was another busy and productive quarter for pipeline advancement at Lilly.

在我們的腫瘤管道中走得更早。作為上週 AACR 會議的一部分，我們展示了 KRASG12C 抑製劑的 I 期研究數據。這些數據顯示出有前途的療效和與 pembrolizumab 聯合使用的差異化安全性的潛力。我們正在努力確定我們的藥物與 pembrolizumab 聯合使用的劑量選擇。在 AACR 上，我們還展示了 CYCLONE 1 的數據，這是一項單臂非盲研究，這是第一個在前列腺癌中研究 Verzenio 的研究。這項早期研究為我們的 CYCLONE 2 適應性 II/III 期試驗的設計提供了信息，該試驗去年清除了我們預設的進入 III 期的門檻，我們預計最快在今年年底宣讀。第一季度是禮來（Lilly）管道推進的另一個繁忙而富有成效的季度。

Now I'll turn the call back to Dave for closing remarks.

現在我將把電話轉回給 Dave，請他作結束語。

Thank you, Dan. Before we go to Q&A, let me briefly sum up our progress to start the year. Our core business, which excludes COVID-19 antibody revenue, grew 10%, driven by Mounjaro, Verzenio, Trulicity and Jardiance. This growth was achieved despite headwinds related to pricing, to generic erosion of Alimta in the U.S. and a moderated but still negative foreign exchange impacts.

謝謝你，丹。在我們進行問答之前，讓我簡要總結一下我們今年的進展情況。在 Mounjaro 、 Verzenio 、 Trulicity 和 Jardiance 的推動下，我們的核心業務（不包括 COVID-19抗體收入）增長了 10%。儘管存在與定價相關的逆風、美國 Alimta 的仿製藥侵蝕以及緩和但仍為負面的外匯影響，但仍實現了這一增長。

In the coming quarters, we expect the impact of COVID-19 antibody revenue in the prior periods will ebb, while our new product and growth product categories of medicines will drive continued revenue growth and meaningful operating margin expansion. While the quarter was not without some challenges, which I am confident we'll overcome, we made meaningful advances in our pipeline, including the approval of an expanded label of Verzenio, the first approval of mirikizumab in Japan, submission of tirzepatide for obesity in the EU and positive results from our second Phase III trial for tirzepatide in obesity.

在未來幾個季度，我們預計 COVID-19 抗體收入對前期的影響將會減弱，而我們的新產品和增長產品類別的藥品將推動持續的收入增長和顯著的營業利潤率擴張。雖然本季度並非沒有一些挑戰，我相信我們會克服這些挑戰，但我們在我們的管道中取得了有意義的進展，包括批准了 Verzenio 的擴展標籤，日本首次批准了 mirikizumab，提交了 tirzepatide 治療肥胖症歐盟和我們的 tirzepatide 在肥胖症中的第二個 III 期試驗的積極結果。

We also demonstrated leadership to improve insulin access and affordability for millions of Americans. Lastly, we returned approximately $1.8 billion to shareholders via the dividend and share repurchase. We remain committed to both executing on the significant opportunities before us and to continuing the important and often difficult work to discover, develop and bring to market innovative medicines to address some of the greatest areas of unmet medical need.

我們還在改善數百萬美國人的胰島素獲取和負擔能力方面發揮了領導作用。最後，我們通過派息和股票回購向股東返還了約 18 億美元。我們仍然致力於抓住擺在我們面前的重大機遇，並繼續開展重要且往往困難重重的工作，以發現、開發創新藥物並將其推向市場，以解決一些未滿足的最大醫療需求領域。

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

現在我將把電話轉給 Joe 來主持問答環節。

Thanks, Dave. We'd like to take questions from as many callers as possible and conclude the call in a timely manner. (Operator Instructions) We're going to end the call at 11:15 a.m. Paul, please provide the instructions for the Q&A session, and we're ready for the first caller.

謝謝，戴夫。我們希望盡可能多地回答來電者的問題，並及時結束通話。 （操作員說明）我們將在上午 11 點 15 分結束通話。保羅，請提供問答環節的說明，我們已準備好迎接第一個來電者。

(Operator Instructions) The first question today is coming from Seamus Fernandez from Guggenheim.

（操作員說明）今天的第一個問題來自古根海姆的 Seamus Fernandez。

So question is for Dan on donanemab. Dan, can you just give us your thoughts on, I guess, what many investors are sort of viewing as the potential Goldilocks scenario that would be necessary to really successfully compete with lecanemab. I'm sure you have your own thoughts on this that are quite detailed. So just wondering how you believe the sort of commercial opportunity and/or really the clinical opportunity is likely to play out once we see the data, assuming the study is positive.

所以問題是關於 donanemab 的 Dan。丹，你能不能告訴我們你的想法，我想，許多投資者認為這是真正成功地與 lecanemab 競爭所必需的潛在金發姑娘情景。我相信您對此有自己的想法，而且非常詳細。所以只是想知道一旦我們看到數據，假設研究是積極的，你如何相信這種商業機會和/或臨床機會真的很可能會發揮作用。

Yes. Thanks, Seamus. I'll start sort of on the data expectations and how it might fit in and maybe Anne will add some things on commercial opportunity. So I think we had very compelling data in Phase II, 32% slowing of disease progression. If in Phase III, we can replicate those kinds of results, this will be a very important and meaningful drug. I know it's interesting for investors to sort of speculate on competition between 2 different pharma companies. It's not exactly how I think about it.

是的。謝謝，西默斯。我將開始討論數據期望以及它如何適應，也許 Anne 會添加一些關於商業機會的內容。所以我認為我們在第二階段有非常令人信服的數據，疾病進展減緩了 32%。如果在第三階段，我們可以復制這些結果，這將是一種非常重要和有意義的藥物。我知道投資者推測兩家不同製藥公司之間的競爭很有趣。這不完全是我的想法。

I think there's a huge opportunity here for patients. The challenge is not really about competition. It's about how do we help the medical system better identify patients, diagnose them and move them into treatment regimens, of course, requiring reimbursement. I think the 2 drugs, however, have some important differences. Donanemab targets specifically amyloid plaques. We think that's the relevant species to hit in Alzheimer's disease. I think we were pretty confident about that in the past, probably the solanezumab data, which targeted just soluble beta adds even more confidence to that statement.

我認為這對患者來說是一個巨大的機會。挑戰與競爭無關。這是關於我們如何幫助醫療系統更好地識別患者、診斷他們並將他們轉移到治療方案中，當然，這需要報銷。然而，我認為這兩種藥物有一些重要的區別。 Donanemab 專門針對澱粉樣斑塊。我們認為這是與阿爾茨海默病相關的物種。我認為我們過去對此非常有信心，可能僅針對可溶性 beta 的 solanezumab 數據為該聲明增添了更多信心。

As a result of hitting just amyloid plaques, that allows us to have fixed duration dosing regimens as an option for patients. Let's see how the data turn out. But I expect that many patients will be able to stop dosing even as soon as 12 months. That's a big difference than being prescribed a drug that you might have to take the rest of your life. And I think that could be exciting and important for patients.

由於僅擊中澱粉樣斑塊，這使我們能夠將固定持續時間的給藥方案作為患者的一種選擇。讓我們看看數據結果如何。但我希望許多患者能夠在 12 個月內停止給藥。這與開出一種你可能不得不終生服用的藥物有很大的不同。我認為這對患者來說可能是令人興奮和重要的。

So lots of ways for donanemab to win. I think the most important thing, though, is showing consistent strong efficacy like we did in Phase II and then getting this drug approved and bringing it to patients. Anne, what do you have?

donanemab 獲勝的方式有很多。不過，我認為最重要的是像我們在第二階段所做的那樣顯示出一致的強大療效，然後讓這種藥物獲得批准並將其帶給患者。安妮，你有什麼？

Thanks, Dan. Yes, we do remain confident in the mid- and long-term opportunity for donanemab. And I think it's important to remember, it will take time to build this market. And so as Dan said, we're investing in these efforts now, building awareness of diagnostics, the awareness of treatments are coming, making sure that the health care systems are ready for these medicines and that the care pathway is set up, and then most importantly, as you said, that patients have access and reimbursement.

謝謝，丹。是的，我們確實對 donanemab 的中長期機會充滿信心。而且我認為重要的是要記住，建立這個市場需要時間。正如 Dan 所說，我們現在正在投資於這些努力，建立診斷意識，治療意識即將到來，確保醫療保健系統為這些藥物做好準備，並建立護理途徑，然後最重要的是，正如您所說，患者可以使用和報銷。

And just to echo his comments, I don't think we really think of this as a cost of drugs we need to fight over market share. It's an opportunity to build a new class on behalf of disease, driving awareness, driving diagnosis and then getting access. So that's important to us in the near term.

只是為了回應他的評論，我不認為我們真的認為這是我們爭奪市場份額所需的藥物成本。這是一個代表疾病建立新課程、提高意識、推動診斷然後獲得訪問權限的機會。所以這在短期內對我們很重要。

The next question is coming from Terence Flynn from Morgan Stanley.

下一個問題來自摩根士丹利的特倫斯弗林。

Maybe 2 part for me. Just I know you're not going to give us a decision on whether you're going to split the tirzepatide brand in 2 here. But maybe you could just talk through some of the key considerations as you think about kind of access side, pricing, IRA, all those things as you just think about the puts and takes. And then on North Carolina manufacturing, just any update on time lines as to when we can expect that to come on board.

也許對我來說是 2 部分。只是我知道你不會讓我們決定你是否要在這裡將 tirzepatide 品牌一分為二。但也許你可以在考慮訪問方、定價、IRA 等所有這些事情時討論一些關鍵考慮因素，就像你考慮看跌期權一樣。然後在北卡羅來納州的製造業，關於我們何時可以預期它會出現的時間表的任何更新。

Thanks, Terence. I'll go to Mike for those questions on branding strategy considerations and then any update on RTP.

謝謝，特倫斯。我將向 Mike 詢問有關品牌戰略考慮因素的問題，然後再向 Mike 詢問有關 RTP 的任何更新。

All right. Thanks, Terence, for that question. On the branding question, obviously, yes, we're not going to provide any clarity on that. I think if you look at the kind of pros and cons on 1 versus 2 brands, the pros are, it is a more efficient supply chain and manufacturing for 1 brand, for 2 brands or some access benefits. Also, you have an empty vessel for the commercial promotion of our obesity indication for -- with the 2-brand scenarios. So that's kind of the puts and takes on that part.

好的。謝謝特倫斯提出這個問題。關於品牌問題，顯然，是的，我們不會對此提供任何明確說明。我認為，如果你看一下 1 個品牌和 2 個品牌的優缺點，優點是，對於 1 個品牌、2 個品牌或一些訪問優勢來說，這是一個更高效的供應鍊和製造。此外，您還有一個空容器用於商業推廣我們的肥胖適應症 - 具有 2 個品牌場景。所以這就是看跌期權並承擔這一部分。

On the supply, I think maybe I'll answer the overall supply question because I'm sure there may be other questions on there. We talked last year that our focus was to double capacity by the end of this year, and we're progressing toward that goal. Our manufacturing team is working hard every day and directly delivering over our manufacturing plan this year. We believe that our channel inventory for Q2 will be a bit better for Mounjaro than what we saw in Q1. And obviously, as you bring up, the important milestone is us bringing our first line of brand fully online this year.

關於供應，我想也許我會回答整體供應問題，因為我確信那裡可能還有其他問題。我們去年談到我們的重點是到今年年底將產能翻一番，我們正在朝著這個目標前進。我們的製造團隊每天都在努力工作，並直接交付了我們今年的製造計劃。我們相信我們第二季度的渠道庫存對於 Mounjaro 來說會比我們在第一季度看到的要好一些。顯然，正如您所說，重要的里程碑是我們今年將我們的第一條品牌線全面上線。

The manufacturing team is progressing toward that goal. And then long term, we're investing where we need to in order to create a long-term significant supply across our entire incretin portfolio to meet what we think is going to just be a tremendous demand globally for the product and for all our incretin portfolio.

製造團隊正在朝著這個目標前進。然後從長遠來看，我們在需要的地方進行投資，以便在我們的整個腸促胰島素產品組合中創造長期的重要供應，以滿足我們認為全球對產品和我們所有腸促胰島素的巨大需求文件夾。

The next question is coming from Chris Schott from JPMorgan.

下一個問題來自摩根大通的 Chris Schott。

Just a 2-parter as well. Can you just maybe talk about bigger picture what you've been seeing in the incretin market? It seems like we first had this nice very strong ramp of Mounjaro, and then we saw a further step-up in category growth with Novo's capacity issues being resolved. So I guess when you're seeing kind of the underlying demand that's out there, is that changing at all how you think about either investing in the space or just your go-to-market strategy for both Mounjaro and then tirzepatide obesity when that's approved?

也只是一個2人。你能談談你在腸促胰島素市場上看到的更大的圖景嗎？似乎我們首先擁有了 Mounjaro 非常強勁的增長，然後隨著 Novo 的產能問題得到解決，我們看到品類增長進一步加快。因此，我想當您看到潛在的需求時，是否會完全改變您對投資該領域的看法，或者只是您對 Mounjaro 和 tirzepatide 肥胖症的上市策略的看法，當它獲得批准時？

I'm just trying to get a sense of just are you -- I think we're all surprised by the volume trends, just how you're kind of adapting within Lilly to kind of think about that beyond just the capacity side, more of the investment side. And then the second question for me on Mounjaro is just can you give a quick update of where we stand right now in terms of use in diabetics versus nondiabetics, given the change in the Bridge program.

我只是想了解一下你 - 我認為我們都對銷量趨勢感到驚訝，你在 Lilly 內部如何適應以超越產能方面的思考，更多投資方面。然後關於 Mounjaro 的第二個問題是，鑑於 Bridge 計劃的變化，你能否快速更新一下我們目前在糖尿病患者和非糖尿病患者中的使用情況。

Thanks, Chris, for the 2-parter there. Mike, we'll go to you for the first part around bigger picture in the incretin market and category growth and how we're thinking about that and then the second round, use in patients with diabetes versus none.

克里斯，謝謝那裡的兩人。邁克，我們將向您介紹第一部分關於腸促胰島素市場和類別增長的大局以及我們如何考慮這一點，然後是第二輪，用於糖尿病患者與無糖尿病患者。

Okay. I'll answer the second question first. With our savings card changes as well as our continued focus of our promotion on only for people with type 2 diabetes, for someone to -- for a new patient to come on to Mounjaro, to have a low out-of-pocket cost, they have to have formulary access. We are only contracting for diabetes access for Mounjaro. So at this point, our assumption is that the vast majority of new people who are new to Mounjaro have type 2 diabetes.

好的。我先回答第二個問題。隨著我們儲蓄卡的變化以及我們繼續專注於僅針對 2 型糖尿病患者的促銷活動，對於某些人來說——對於來到 Mounjaro 的新患者來說，自付費用較低，他們必須具有處方訪問權限。我們只為 Mounjaro 的糖尿病患者提供服務。所以在這一點上，我們的假設是，絕大多數剛接觸 Mounjaro 的新人都患有 2 型糖尿病。

On the incretin market, yes, it's really growing both across type 2 diabetes. It's really surge as well as on the obesity front. We plan to aggressively promote and offer this product in both disease classes and invest appropriately to the opportunity. We're not surprised by the market growth in type 2 diabetes. We think there's a big opportunity to really help people who have type 2 diabetes early in the course of treatment to improve their long-term health outcomes.

是的，在腸促胰島素市場上，它在 2 型糖尿病中確實在增長。它在肥胖方面確實激增。我們計劃在兩種疾病類別中積極推廣和提供該產品，並適當投資機會。我們對 2 型糖尿病的市場增長並不感到驚訝。我們認為有很大的機會在治療過程的早期真正幫助患有 2 型糖尿病的人改善他們的長期健康結果。

And then as the SURMOUNT-2 data demonstrated, there's just a tremendous unmet need in the obesity market. And we're not surprised by Wegovy's uptake after the resupply and relaunch. And I just really think it really points to the tremendous opportunity that we have to really help patients and meet the needs of the marketplace. So really no changes for us. We felt that both markets would have good growth opportunities. We're prepared to be successful and both grow the market and grow our share in type 2 diabetes and then establish ourself in the chronic weight management market.

然後正如 SURMOUNT-2 數據所表明的那樣，肥胖市場存在巨大的未滿足需求。我們對 Wegovy 在補給和重新啟動後的接受度並不感到驚訝。我只是真的認為它確實指出了我們必須真正幫助患者並滿足市場需求的巨大機會。所以對我們來說真的沒有變化。我們認為這兩個市場都有良好的增長機會。我們已準備好取得成功，同時擴大市場並擴大我們在 2 型糖尿病領域的份額，然後在慢性體重管理市場站穩腳跟。

The next question is coming from Colin Bristow from UBS.

下一個問題來自瑞銀的 Colin Bristow。

Congrats on the quarter and the SURMOUNT-2 data. So on Mounjaro, I think it's comforting to see handsomely step-up from 4Q. I was wondering, can you help us think about the sort of continued cadence of improvement over the balance of the year? And then more importantly, how should we think about gross to net post approval in obesity? Is it reasonable to expect another kind of step down temporarily? Or would that not be the case? And then just on the Mounjaro and obesity, can you just walk us through the anticipated time lines here and the potential use of a priority review voucher?

祝賀本季度和 SURMOUNT-2 數據。因此，在 Mounjaro 上，我認為看到從 4Q 開始大幅提升是令人欣慰的。我想知道，你能幫我們想想在今年餘下的時間裡持續改進的節奏嗎？然後更重要的是，我們應該如何考慮肥胖症的總批准後淨值？期待另一種暫時的下台是否合理？還是不是這樣？然後就 Mounjaro 和肥胖問題，您能否帶我們了解這裡的預期時間表以及優先審查憑證的潛在用途？

Okay. Mike, you can go ahead and cover these points kind of general gross to net thoughts and trends and then Colin's question about potential use of a priority review voucher.

好的。邁克，你可以繼續討論這些要點，從總體到淨的想法和趨勢，然後是科林關於優先審查憑證的潛在用途的問題。

Okay, appreciate that. On the gross to net progression for Mounjaro, I think it's best to look at our paid TRxs, which we define as those patients who's not supported by our $25 noncoverage savings program. That was our original program at launch. You see from the slide that Anat presented early on that we have seen just really good growth of the paid TRxs over time. If you take a look at the growth from Q1 versus Q4, it was a 55% growth in paid TRxs.

好的，謝謝。關於 Mounjaro 從毛額到淨額的進展，我認為最好看看我們的付費 TRx，我們將其定義為那些不受我們 25 美元非保險儲蓄計劃支持的患者。那是我們在發佈時的原始程序。從 Anat 早些時候展示的幻燈片中可以看出，隨著時間的推移，我們已經看到付費 TRx 的增長非常好。如果你看一下第一季度與第四季度的增長情況，付費 TRx 增長了 55%。

If you look at the point in time of the week before we started the saving card changes to last week, we've increased paid TRx growth by almost 2.5x. So we're very happy with that. That's the trend we need to see to improve gross to net. Now at the same time, we look at kind of what we've defined as unpaid scripts, which is those that are supported by the original $25 noncoverage savings programs, those are decreasing. So really, that's the 2 trends you need to see to lead to improved growth to net of paid scripts increasing and unpaid scripts decreasing.

如果您查看我們開始對上週進行儲蓄卡更改之前的一周時間點，我們已經將付費 TRx 增長提高了近 2.5 倍。所以我們對此非常滿意。這是我們需要看到的趨勢，以提高毛淨收入。現在與此同時，我們看一下我們定義為無償腳本的類型，即那些由最初的 25 美元非覆蓋儲蓄計劃支持的腳本，這些腳本正在減少。所以真的，這是你需要看到的 2 種趨勢，以導致付費腳本增加和未付費腳本減少的淨增長。

Also, we expect those trends to continue. We also have a milestone coming up at the end of June when the original $25 noncovered savings card are set to expire. With chronic weight management approval, we'll talk about that -- and pricing at the appropriate time after approval. With regards to our submission, chronic weight management, our plan, as Dave said, the team is taking this data right now and working feverishly to submit that in the coming weeks.

此外，我們預計這些趨勢將繼續下去。我們還將在 6 月底迎來一個里程碑，屆時原始的 25 美元非承保儲蓄卡將到期。在獲得慢性體重管理批准後，我們將討論這一點——並在批准後的適當時間進行定價。關於我們的提交、慢性體重管理、我們的計劃，正如 Dave 所說，團隊現在正在收集這些數據，並在未來幾週內狂熱地提交這些數據。

We do have Fast Track designation from the FDA to expect that -- to expedite it. We have a rolling submission. We already submitted the SURMOUNT-1 data. And we are excited to also talk about that. While we think the FDA will act quickly with the Fast Track designation, we want to remove any uncertainty. And so we will be using a PRV and expect that we'll get approval as early as the end of this year.

我們確實獲得了 FDA 的快速通道指定，希望能夠加快速度。我們有滾動提交。我們已經提交了 SURMOUNT-1 數據。我們也很高興談論這一點。雖然我們認為 FDA 會迅速採取快速通道指定，但我們希望消除任何不確定性。因此，我們將使用 PRV，並預計我們最早將於今年年底獲得批准。

The next question is coming from Evan Seigerman from BMO Capital Markets.

下一個問題來自 BMO Capital Markets 的 Evan Seigerman。

First off, congrats on the great data today. Very exciting for patients. Just taking a step back, I'd love to get some color as to how Lilly plans to balance the commercial potential of Mounjaro in both diabetes and obesity with estimates that really could best the top-selling pharmaceutical products now without overstressing the U.S. health care system, especially essentially balancing volume and cost to the system.

首先，祝賀今天的大數據。對患者來說非常令人興奮。退後一步，我很想了解禮來公司計劃如何平衡 Mounjaro 在糖尿病和肥胖症方面的商業潛力，並估計它確實可以成為現在最暢銷的藥品，而不會給美國醫療保健帶來過大壓力系統，特別是基本上平衡系統的體積和成本。

Thanks, Evan, for the question. Mike, we'll go back to you balancing commercial potential with potential stress to the system. Thoughts?

謝謝埃文提出這個問題。邁克，我們會回來找你平衡商業潛力和對系統的潛在壓力。想法？

Yes, it's a good question. Again, when we look at the opportunity within, let's say the chronic weight management marketplace, it's easy to look at the number of people who live with obesity both in the U.S. and globally, and look at, boy, this could have a big impact on health care costs. But I think if you look more at the real true potential that we focus so much on weight loss, but when you look at not only the -- what does weight loss really provide, there's over 200 complications associated with living with obesity.

是的，這是個好問題。同樣，當我們審視其中的機會時，比方說長期的體重管理市場，很容易看到美國和全球肥胖症患者的數量，然後看看，男孩，這可能會產生很大的影響關於醫療保健費用。但我認為，如果你更多地關注我們如此關注減肥的真正潛力，但當你不僅關注——減肥真正提供了什麼，還有超過 200 種與肥胖相關的並發症。

And as we get more and closer to the marketplace and look at our modeling, we do think that this is going to relieve and reduce the risk of complications associated with obesity, and there will be medical cost savings associated with using these agents, which will, I think, be of great societal value.

隨著我們越來越接近市場並查看我們的模型，我們確實認為這將減輕和降低與肥胖相關的並發症的風險，並且將節省與使用這些藥物相關的醫療費用，這將，我認為，具有很大的社會價值。

Also, when you look at the quality of life results that we saw from SURMOUNT-1, they were remarkable. And at times, it's hard to quantify those in a cost-effectiveness model. But in real life, those impact patients significantly. And I think it really does highlight how important these treatments are to people who live with obesity. And so I think as you look at the impact not at like a population level but on a patient level, these agents on tirzepatide will provide great value to society.

此外，當您查看我們從 SURMOUNT-1 中看到的生活質量結果時，它們非常出色。有時，很難在成本效益模型中量化這些。但在現實生活中，這些對患者的影響很大。我認為它確實突出了這些治療對肥胖患者的重要性。因此，我認為，當您不是從人口層面而是從患者層面來看待影響時，tirzepatide 上的這些藥物將為社會提供巨大的價值。

Yes. Maybe just to add, I think the latest data from the Medicare Trust is that we're spending about $1 trillion a year as a country on obesity-related complications and comorbidities. I don't think we always do a very good job of thinking about buying pharmaceuticals as an investment and future savings in our health. Maybe we do better when it's acute like COVID. I think we spent tens of billions on COVID therapies and didn't question it as much.

是的。也許只是補充一下，我認為來自 Medicare Trust 的最新數據表明，作為一個國家，我們每年在與肥胖相關的並發症和合併症上花費大約 1 萬億美元。我不認為我們總是很好地考慮購買藥品作為對我們健康的投資和未來儲蓄。也許當它像 COVID 一樣嚴重時我們會做得更好。我認為我們在 COVID 療法上花費了數百億美元，但並沒有那麼多質疑。

But here's -- I think even in the most rosy forecast, we're not going to sell $1 trillion of obesity drugs. So the question is more like, over time, can we demonstrate that treatment today reduces cost downstream? We're highly confident that, that will be a multiple of 5x, 10x savings for whatever people invest in the medicines. We have to prove that. That's our job as an innovative company is to do the outcome studies that demonstrate that. I think our competitors are doing the same thing, and that will be good for the field.

但這裡——我認為即使是最樂觀的預測，我們也不會賣出 1 萬億美元的減肥藥。所以問題更像是，隨著時間的推移，我們能否證明今天的治療可以降低下游成本？我們非常有信心，無論人們在藥物上投資多少，都將節省 5 倍、10 倍的費用。我們必須證明這一點。作為一家創新型公司，我們的工作就是進行結果研究來證明這一點。我認為我們的競爭對手也在做同樣的事情，這對這個領域來說是件好事。

And as I've said before, it's hard to imagine by the end of this decade that everyone doesn't just accept that pharmacologic treatment for overweight and obesity should be the standard of care, and it will save this health care system trillions of dollars over time. So that's our position and we need to fight for that position. We also need to do the work. And right now, we are talking about weight loss numbers, not outcomes. But that data is coming soon, as early as next year for tirzepatide.

正如我之前所說，很難想像到本世紀末，每個人都不會接受超重和肥胖的藥物治療應該成為標準治療，這將為醫療保健系統節省數万億美元隨著時間的推移。所以這就是我們的立場，我們需要為這個立場而戰。我們也需要做這項工作。現在，我們談論的是減肥數字，而不是結果。但該數據很快就會出現，最早將於明年提供 tirzepatide。

The next question is coming from Chris Shibutani from Goldman Sachs.

下一個問題來自高盛的 Chris Shibutani。

With and thinking about its safety tolerability profile, I think we have a base level of precedent data that sort of frames expectations for what the ARIA rates are, including last fall when you have the head-to-head for adjuvant where I think there was some relative improvement, recognizing that there's difference in patient populations.

考慮到它的安全耐受性概況，我認為我們有一個基本水平的先例數據，可以構建對 ARIA 比率的預期，包括去年秋天當你有佐劑的正面交鋒時，我認為有一些相對的改善，認識到患者群體存在差異。

Now that you're doing this TRAILBLAZER-ALZ 6 study, there's aspects of this where you have dosing intervals that include placebo. You also talked about using blood-based biomarkers. Can you help us frame expectations for what would be a meaningful differential? Should we have baseline expectations that reflect more of the prior data? Or is there really room to improve?

既然您正在進行這項 TRAILBLAZER-ALZ 6 研究，那麼在這方面您的給藥間隔包括安慰劑。您還談到了使用基於血液的生物標誌物。你能幫助我們構建對有意義的差異的期望嗎？我們是否應該有反映更多先前數據的基線預期？或者真的有改進的餘地嗎？

And when you think about all of these MRI and blood-based biomarkers, how much is this going to be sort of logically natural relative to how patients are cared for? Or is this also going to require some threading in of new ways that patients are managed, which I know that you're investing tremendously in? But just help us with the logic of results from these studies like TB6.

當你考慮所有這些 MRI 和基於血液的生物標誌物時，相對於患者的護理方式，這在邏輯上有多少是自然的？或者這是否也需要採用一些新的方式來管理患者，我知道你在這方面投入了大量資金？但是，請幫助我們了解這些研究（如 TB6）的結果邏輯。

Thanks, Chris. That's a lot to unpack in the question, but I'll hand over to Dan for some commentary on TB6.

謝謝，克里斯。這個問題有很多要解開的問題，但我將交給 Dan 對 TB6 進行一些評論。

No. Thanks, Chris. I'm glad you raised this. It's a topic that we think a lot about. Probably just starting with maybe correcting a misperception in the field around ARIA rates, I think we don't really know what asymptomatic ARIA means is sort of an incidental finding on an advanced brain scan. We don't want to over-index on that. We want to focus on symptomatic ARIA. And symptomatic ARIA rates, that's what the patient experiences is adverse is a range from sort of 5% to 10% or less across the class.

不，謝謝，克里斯。很高興你提出這個問題。這是一個我們經常思考的話題。可能只是從糾正該領域對 ARIA 率的誤解開始，我認為我們真的不知道無症狀 ARIA 意味著什麼是高級腦部掃描的偶然發現。我們不想對此過度索引。我們想專注於有症狀的 ARIA。有症狀的 ARIA 率，即患者經歷的不利情況，在整個班級中範圍從 5% 到 10% 或更低。

We don't understand all the factors that could cause 1 patient of symptomatic ARIA and another patient to have a symptomatic ARIA, which we see is not a problem. That's what we want to understand better in this study. Are there things that we can see on baseline MRIs or on blood biomarkers that might predict who's going to have those symptomatic ARIAs? And then are there adjustments to dosing that you could have in those patients so they can still get the benefit of the drug without getting the symptomatic ARIA?

我們不了解可能導致 1 名症狀性 ARIA 患者和另一名患者出現症狀性 ARIA 的所有因素，我們認為這不是問題。這就是我們希望在這項研究中更好地理解的內容。我們是否可以在基線 MRI 或血液生物標誌物上看到可以預測誰將患有這些症狀性 ARIA 的東西？然後，您是否可以對這些患者進行劑量調整，以便他們仍然可以在不出現症狀性 ARIA 的情況下獲得藥物的益處？

I don't see this as a study where there's a positive outcome or a negative outcome. It's not a binary thing here. What it's going to do is add to our understanding of how best to identify patients and how best to change dosing in patients who have the highest risk that overall, that should lead the field to have more comfort using these drugs, the entire class of drugs probably in more responsible ways.

我不認為這是一項有積極結果或消極結果的研究。這不是二進制的東西。它要做的是增加我們對如何最好地識別患者以及如何最好地改變總體風險最高的患者的劑量的理解，這應該導致該領域更舒適地使用這些藥物，整個類別的藥物可能以更負責任的方式。

The next question is coming from Geoff Meacham from Bank of America Merrill Lynch.

下一個問題來自美銀美林的 Geoff Meacham。

Congrats on the data. Just have a couple of related ones for Dan. On SURMOUNT-4, I know we don't have data yet but are there lessons to be learned commercially about the rebound effect once you discontinue tirzepatide? And just wasn't sure what your thoughts of on continuity of therapy in the real world. And the second 1 is that when you think about tirzepatide development in other settings like sleep apnea, et cetera, there are a lot of indications that you could still go after but haven't officially announced When you look outside of diabetes or obesity, what is the criteria for selecting tirzepatide development versus, say, the oral versus GGG, et cetera?

恭喜數據。只為丹準備幾個相關的。在 SURMOUNT-4 上，我知道我們還沒有數據，但是一旦你停止使用 tirzepatide，是否有關於反彈效應的商業經驗教訓？只是不確定您對現實世界中治療連續性的看法。第二個 1 是當你考慮 tirzepatide 在睡眠呼吸暫停等其他環境中的發展時，有很多跡象表明你仍然可以追求但尚未正式宣布當你在糖尿病或肥胖之外看時，什麼選擇 tirzepatide 開發與口服與 GGG 等的標準是什麼？

Thanks, Geoff. Go ahead, Dan.

謝謝，傑夫。去吧，丹。

Okay, I'll start and I'll let Mike follow up on commercial questions here. Starting with your question on SURMOUNT-4, sort of asking what are our expectations and implications of what happens when people come off this drug, I think unfortunately, tirzepatide is probably like every other drug we have, which is requires you to take it to continue to get the benefits. That's the expectation we have for blood pressure drugs and lipid-lowering drugs and probably we should have that for some time for drugs to manage obesity.

好的，我會開始，我會讓 Mike 跟進這裡的商業問題。從你關於 SURMOUNT-4 的問題開始，有點問我們對人們停止使用這種藥物後會發生什麼的期望和影響，我認為不幸的是，tirzepatide 可能就像我們擁有的所有其他藥物一樣，這需要你服用它繼續領取福利。這是我們對降壓藥和降脂藥的期望，也許我們應該對控制肥胖的藥物有一段時間的期望。

What does that mean in the real world for patients? My expectation is many patients may try coming off the drug completely to see what happens. Maybe some will be successful in maintaining their weight, but many of them will probably experience some regression of their weight back towards baseline. And this could prompt them to come back on the drug. That's probably natural and we can expect that, although Mike will comment in a second on commercial dynamics.

這在現實世界中對患者意味著什麼？我的期望是許多患者可能會嘗試完全停藥以查看會發生什麼。也許有些人會成功地保持體重，但他們中的許多人可能會經歷一些體重回歸基線的過程。這可能會促使他們重新服用藥物。這可能是自然的，我們可以預料到，儘管 Mike 稍後會就商業動態發表評論。

In terms of other indications, we really look at things that could have a big impact via weight loss. There's never been a drug like tirzepatide that can cause this amount of weight loss. So mostly, we're looking through literature on things like bariatric surgery and seeing what kind of benefits that can lead to or diet and exercise. And that's how we've gotten to a few indications that you mentioned, sleep apnea and heart failure, among others.

就其他跡象而言，我們真正關注的是可能通過減肥產生重大影響的事情。從來沒有像 tirzepatide 這樣的藥物可以導致如此多的體重減輕。因此，大多數情況下，我們正在查閱有關減肥手術等方面的文獻，看看節食和鍛煉可以帶來什麼樣的好處。這就是我們如何得到你提到的一些跡象，睡眠呼吸暫停和心力衰竭等。

In terms of which drug could be best right now, of course, we have the most confidence around tirzepatide, but there might be some indications where a drug like retatrutide, which adds glucagon and call it GGG, could be better. For example, glucagon has profound effects on fat in the liver, so maybe that plays better for complications of obesity related to liver disease like NASH.

關於目前哪種藥物最好，當然，我們對 tirzepatide 最有信心，但可能有一些跡象表明像 retatrutide 這樣的藥物可能更好，它添加了胰高血糖素並稱之為 GGG。例如，胰高血糖素對肝臟中的脂肪有深遠的影響，因此它可能更適合與 NASH 等肝病相關的肥胖並發症。

Orforglipron, on the other hand, our oral, unlikely to have as much weight loss as profound metabolic improvements as tirzepatide does because it doesn't have any GIP, which is an important constituent of tirzepatide. But on the other hand, the ease of use may make it more applicable to some broader, more primary care indications. So that's a little bit of thinking on how we sort those out. Mike?

另一方面，Orforglipron，我們的口服藥物，不太可能像 tirzepatide 那樣具有顯著的代謝改善那麼多的減肥效果，因為它沒有任何 GIP，而 GIP 是 tirzepatide 的重要成分。但另一方面，易用性可能使其更適用於一些更廣泛、更初級的醫療適應症。所以這是關於我們如何解決這些問題的一些思考。麥克風？

Yes. On the commercial side, as we launch into the chronic weight management market for tirzepatide, we'll be very upfront with payers and health care professionals and consumers that this is a chronic disease and a chronic medication that needs to be adhered to long term. When you look at how this product works, one of the most important aspects of it is that it controls and reduces appetite. When someone tries to gain -- to lose weight via diet and exercise, as someone is successful in losing weight, the body actually works against that and tugs it the opposite way by increasing the appetite.

是的。在商業方面，當我們進入 tirzepatide 的慢性體重管理市場時，我們將非常坦率地向付款人、醫療保健專業人員和消費者表明這是一種慢性疾病和需要長期堅持的慢性藥物。當您查看該產品的工作原理時，它最重要的方面之一就是它可以控制和減少食慾。當有人試圖通過節食和運動來增重時，當有人成功減肥時，身體實際上會與之抗衡，並通過增加食慾來以相反的方式拉動它。

That's why these agents, tirzepatide does work because it does reduce the appetite. So while on therapy, we anticipate that the appetite will be lowered and maintained. And then if stopped, then the appetite will increase. Now this is something that unlike most drugs, you don't know if you stop taking like a statin or something else, you don't really feel any effects. We do think that, that will be a noticable effect that will begin soon after stopping therapy even before you start seeing weight gain. So I think we think that will be an important kind of signal for a patient to understand that this is a chronic disease and needs to be treated long term.

這就是為什麼這些藥物 tirzepatide 確實有效，因為它確實會降低食慾。因此，在接受治療時，我們預計食慾會降低並保持不變。然後如果停止，食慾就會增加。現在這是與大多數藥物不同的東西，你不知道如果你停止服用他汀類藥物或其他藥物，你不會真正感受到任何影響。我們確實認為，這將是一個顯著的效果，即使在您開始看到體重增加之前停止治療後很快就會開始。所以我認為我們認為這將是一種重要的信號，讓患者了解這是一種慢性疾病，需要長期治療。

As it goes into the -- maybe 1 other aspect on the additional indications, we talk a lot about access and the need for in order to get access into Part D. And obviously, that will be an important thing overarching. But these additional indications are important for the senior population. Complications run with living with obesity, and they emerge into complications when you reach Medicare like type 2 diabetes, like sleep apnea and like heart failure.

當它進入 - 可能是關於其他指示的另一個方面時，我們談論了很多關於訪問和訪問 D 部分的必要性。顯然，這將是一件重要的事情。但這些額外的適應症對老年人群很重要。並發症伴隨著肥胖，當你獲得 2 型糖尿病、睡眠呼吸暫停和心力衰竭等醫療保險時，它們就會出現並發症。

And so we believe these are important indications to study because we think these are important health conditions. But also commercially, we think this is important because this will help us get access for these really important complications that are really important to the senior population. So commercially, we think these are really important. Thanks for the question.

因此，我們認為這些是需要研究的重要指標，因為我們認為這些是重要的健康狀況。但在商業上，我們認為這很重要，因為這將幫助我們獲得對老年人群非常重要的這些非常重要的並發症。所以在商業上，我們認為這些非常重要。謝謝你的問題。

The next question is coming from Umer Raffat from Evercore ISI.

下一個問題來自 Evercore ISI 的 Umer Raffat。

I have a question on drug pricing, especially as it relates to Mounjaro. A, what's your expectation on net price per patient beyond the first year on Mounjaro? And I realize the compliance as well as maintenance pricing would be considerations. And secondly, in a scenario where Ozempic and Trulicity are in the IRA basket in 2027, should it be our base case that there would not be an impact to the non-Medicare book of business? And would it not impact other members in the class like Mounjaro? I feel like it's not super clear. I'd be curious about your thoughts.

我對藥品定價有疑問，尤其是與 Mounjaro 相關的問題。 A，您對 Mounjaro 第一年後每位患者的淨價格有何期望？我意識到合規性和維護定價將是考慮因素。其次，在 Ozempic 和 Trulicity 在 2027 年加入 IRA 籃子的情況下，我們的基本情況是否應該是不會對非醫療保險業務產生影響？會不會像 Mounjaro 一樣影響班上的其他成員？我覺得不是很清楚。我很好奇你的想法。

Thanks, Mike. I'm sorry. Thanks, Umer. I'll maybe go to Mike for the kind of question about net pricing on Mounjaro and how that might evolve and then also on general commentary around if Ozempic is in the IRA basket, what might the impact be to others. Mike?

謝謝，邁克。對不起。謝謝，烏默爾。我可能會向 Mike 詢問有關 Mounjaro 淨定價的問題，以及它可能如何演變，然後再就 Ozempic 是否在 IRA 籃子中，可能對其他人產生什麼影響進行一般性評論。麥克風？

Yes. No, good question. I mean, on net pricing, we have 1 price point for Mounjaro. We have flat pricing across the dosing form so people can feel free to find the right dose that works for them at the same price. That will be the same price for new starts, it is for people on maintenance to treatment.

是的。不，好問題。我的意思是，在淨定價方面，我們有 1 個 Mounjaro 的價格點。我們對所有劑量形式實行統一定價，因此人們可以放心地以相同的價格找到適合他們的合適劑量。這將是新開始的相同價格，它適用於維持治療的人。

Yes. And if I got your question right and just to clarify, it's not clear to us that semaglutide and dulaglutide will be eligible in the same year for IRA, if they're eligible, depending on sales 2 years prior in the various ways the government is proposing to do this. But let's just play it out if sema is selected because it's a small molecule 9 years from launch, et cetera. What will happen in the commercial market? Nobody knows because in the draft guidance, there really isn't a lot of clarity about how the government proposes to effectuate the so-called maximum fair price to the consumer level.

是的。如果我答對了你的問題並澄清一下，我們不清楚索馬魯肽和度拉糖肽是否在同一年有資格獲得 IRA，如果它們符合條件，這取決於 2 年前政府以各種方式進行的銷售提議這樣做。但是，如果選擇了 sema，我們就試一試吧，因為它是一個小分子，距離發射 9 年等等。商業市場會發生什麼？沒有人知道，因為在指南草案中，政府提議如何將所謂的最大公平價格落實到消費者層面，確實沒有太多的清晰度。

They're entertaining a few ideas, it appears, from their initial guidance. I think we're expecting more regulatory, either definitive regulatory statements or proposals for comment in the coming 90 days, Umer. But I can tell you what we'd prefer is that since we're not a party to that transaction as manufacturers in this example, not us, but someone else, we would probably need a third party to determine, is that a valid Part D prescription? Is it eligible for the maximum fair price? And then to step in and match that transaction up post hoc.

看來，他們從最初的指導中得到了一些想法。 Umer，我認為我們期待在未來 90 天內有更多的監管，無論是明確的監管聲明還是徵求意見的建議。但我可以告訴你我們更喜歡的是，因為在這個例子中我們不是作為製造商的交易的一方，不是我們，而是其他人，我們可能需要第三方來確定，是一個有效的部分D處方？它是否有資格獲得最高公平價格？然後介入並事後匹配該交易。

We did something like that when the donut hole was created, and it worked pretty well with third-party administrators. This is what we've suggested that the administration will be the best thing. And in that scenario, you would not have a wholesale price reduction to reach the maximum fair price. You would do it after the fact, and I think in that way, be able to keep the 2 segments, commercial and government a little bit more separate. That has obvious advantage for the industry and probably for payers as well and maybe for patients, creating certainty and lack of arbitrage across physical distribution channels. So to be determined there, but as that detail comes out, we'll have more commentary on it, but ball's in the government's court now.

我們在創建甜甜圈洞時做了類似的事情，並且它與第三方管理員一起工作得很好。這就是我們建議的政府將是最好的事情。在這種情況下，您不會為了達到最高公平價格而降低批發價。你會在事後這樣做，我認為這樣可以將商業和政府這兩個部分分開一些。這對行業、可能對付款人以及患者都有明顯的優勢，從而在實體分銷渠道中創造確定性和缺乏套利。所以要在那裡確定，但隨著細節的出現，我們將對此進行更多評論，但球現在在政府的法庭上。

The next question is coming from Tim Anderson from Wolfe Research.

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

I wanted to ask some questions about the obesity opportunity in ex U.S. markets because I know it seems like all the discussion is about the U.S. markets. But in your opinion, how will it play out ex U.S. relative to the U.S. when you think about obesity over the longer term? To me, it seems like payers are likely to be much more restrictive ex U.S. with a product like this. Is that a fair characterization? Or do you think low enough pricing will fully offset any sort of hesitation and basically open up the markets equally like it will happen in the U.S.?

我想問一些關於美國市場以外的肥胖機會的問題，因為我知道似乎所有的討論都是關於美國市場的。但在您看來，當您從長遠考慮肥胖問題時，相對於美國而言，美國以外的情況會如何發展？在我看來，對於這樣的產品，美國以外的付款人可能會更加嚴格。這是一個公平的表徵嗎？還是您認為足夠低的定價將完全抵消任何形式的猶豫並基本上像美國一樣開放市場？

Thanks, Tim, for the really good question. I'll hand over to Ilya Yuffa, our President of Lilly International to weigh in on that.

謝謝，蒂姆，提出了一個非常好的問題。我將交給我們的禮來國際總裁 Ilya Yuffa 來權衡這一點。

Tim, thanks for the question. As we take a look at the chronic weight management market internationally outside the U.S., it's a significant opportunity. We already see significant utilization of current therapies that don't provide as much weight loss and benefit and still providing significant commercial opportunity and also access to patients. A lot of that is happening in many markets out of pocket.

蒂姆，謝謝你的提問。當我們審視美國以外的國際長期體重管理市場時，這是一個重要的機會。我們已經看到當前療法的大量利用，這些療法不能提供那麼多的減肥效果和益處，但仍提供重要的商業機會和患者接觸。許多市場都是自掏腰包發生的。

At the same time, there are markets that are already moving towards reimbursement, U.K. and other markets in Europe, already looking at ways to reimburse, especially in the higher BMI categories of obesity. And so this will play out over time on both as we look at data and outcomes to drive further an expansion of access. And also, we do foresee a significant out-of-pocket market in many countries, including Asia, South America and Europe as well.

與此同時，一些市場已經在朝著報銷方向發展，英國和歐洲其他市場已經在尋找報銷方式，尤其是在 BMI 較高的肥胖類別中。因此，隨著時間的推移，這將在我們查看數據和結果以進一步擴大訪問範圍時發揮作用。而且，我們確實預見到許多國家（包括亞洲、南美和歐洲）都有一個重要的自付費用市場。

And so I think you'll see that grow over time, but significant opportunity to take a look at the total population globally that is obese, overweight, there's a significant opportunity outside of the U.S. for chronic weight management, and we'll look to invest in expanding that both the introduction of Mounjaro tirzepatide in chronic weight management but also improving access over time.

所以我認為你會看到隨著時間的推移而增長，但這是一個重要的機會來了解全球肥胖、超重的總人口，在美國以外的地區也有一個重要的長期體重管理機會，我們將期待投資擴大 Mounjaro tirzepatide 在慢性體重管理中的引入，同時隨著時間的推移改善可及性。

Thanks, Ilya, and thanks, Tim, for the question. Running low on time, so we'll try to get through as many questions as possible. Paul, next question.

謝謝 Ilya，也謝謝 Tim 提出的問題。時間不多了，所以我們會盡量解決盡可能多的問題。保羅，下一個問題。

The next question is coming from Steve Scala from Cowen.

下一個問題來自 Cowen 的 Steve Scala。

I appreciate that data presentation is key to fully answering the question, but what opportunities are still available to Verzenio in the adjuvant setting now that we have seen the top line of NATALEE? It would be easy to conclude NATALEE is a significant risk to Verzenio adjuvant use and that Verzenio adjuvant use will decline. What other scenarios would you like us to consider? And what aspects of NATALEE would you like to highlight?

我很欣賞數據呈現是完全回答這個問題的關鍵，但既然我們已經看到了 NATALEE 的頂線，Verzenio 在輔助環境中還有哪些機會可用？很容易得出結論，NATALEE 對 Verzenio 佐劑的使用具有重大風險，並且 Verzenio 佐劑的使用將會減少。您希望我們考慮哪些其他情況？您想強調 NATALEE 的哪些方面？

Thanks, Steve, for the question. I'll hand over to Jake Van Naarden to weigh in on the opportunity.

謝謝史蒂夫提出這個問題。我將交給 Jake Van Naarden 來權衡這個機會。

Yes. Thanks, Steve for the question. I'm not sure I agree with your framing, I'm not sure we agree. The NATALEE success is not really a surprise to us. We said publicly, we expected it to be positive. We frankly thought it would be positive actually at the last interim analysis at the end of last year. Just by way of reminder, we studied Verzenio in the adjuvant setting, given for 2 years, specifically in a high-risk population, which is a population that we and I think physicians agree is the 1 that really requires intensification of therapy. And now Verzenio is the standard of care in that setting.

是的。謝謝，史蒂夫的問題。我不確定我是否同意你的框架，我不確定我們是否同意。 NATALEE 的成功對我們來說並不意外。我們公開表示，我們預計這是積極的。我們坦率地認為，在去年年底的最後一次中期分析中，這實際上是積極的。提醒一下，我們在輔助環境中研究了 Verzenio，為期 2 年，特別是在高危人群中，我們和我認為醫生認為這是真正需要加強治療的人群。現在 Verzenio 是該環境中的護理標準。

We don't really expect that to change actually. We have mature follow-up on our data as last presented at San Antonio in December. We have a Category 1 NCCN listing for Verzenio in the setting. I think Verzenio's role in high-risk adjuvant endocrine positive breast cancer is pretty clear. We seem to hear a lot of noise about ribociclib in intermediate risk population, a population that we didn't study, a population for whom I think the risk benefit is a little bit more questionable.

我們真的不希望這種情況發生實際變化。我們對去年 12 月在聖安東尼奧提交的數據進行了成熟的跟進。我們在設置中有 Verzenio 的 1 類 NCCN 列表。我認為 Verzenio 在高危輔助內分泌陽性乳腺癌中的作用非常明確。我們似乎在中等風險人群中聽到了很多關於 ribociclib 的噪音，我們沒有研究這個人群，我認為對這些人群的風險收益有點值得懷疑。

And to the extent that the data we see at ASCO provides a role for that drug in that setting, sure. That's fine. That really doesn't pose any threat to the forecasted opportunity for Verzenio in the high-risk setting where we still remain very confident in its prospects.

當然，就我們在 ASCO 上看到的數據為該藥物在那種情況下發揮的作用而言。沒關係。這確實不會對 Verzenio 在高風險環境中的預測機會構成任何威脅，我們仍然對其前景充滿信心。

The next question is coming from David Risinger from SVB Securities.

下一個問題來自 SVB Securities 的 David Risinger。

So congrats on all the updates. I just wanted to get your take on Novo's, Wegovy-SELECT cardiovascular outcomes trial and potential implications. So I think expectations are that the efficacy could be modest. Could you comment on that scenario and then also comment on the scenario that the trial surprisingly fails?

所以恭喜所有的更新。我只是想听聽您對 Novo 的 Wegovy-SELECT 心血管結局試驗及其潛在影響的看法。所以我認為預期效果可能是適度的。您能否評論一下這種情況，然後再評論一下試驗意外失敗的情況？

Thanks, Steve. I'll hand over to Dan for a quick thought on that.

謝謝，史蒂夫。我將交給 Dan 快速考慮一下。

Thanks, Dave. Maybe some of those questions are better addressed to Novo. I think based on passing an interim without stopping early, you can sort of put an upper limit on how good the efficacy could be. But we don't know exactly what that will be. I expect I think most people reasonably expect the trial will be positive. We know that weight loss has so many benefits, including cardiovascular benefits, and that's likely to be demonstrated in a large clinical trial.

謝謝，戴夫。也許其中一些問題最好向 Novo 提出。我認為基於在不提前停止的情況下通過過渡期，你可以對療效的好壞設置一個上限。但我們不知道那會是什麼。我希望我認為大多數人都合理地期望試驗會是積極的。我們知道減肥有很多好處，包括對心血管的好處，這很可能會在大型臨床試驗中得到證明。

No idea what the number will be here, the stats or anything like that. But I'll be surprised if weight loss doesn't translate into benefits. We, of course, have our own studies going both in the type 2 and diabetes population and in the obesity population. We'll look forward to those outcomes.

不知道這裡會有什麼數字，統計數據或類似的東西。但如果減肥沒有轉化為好處，我會感到驚訝。當然，我們在 2 型糖尿病人群和肥胖人群中都有自己的研究。我們將期待這些結果。

The next question is coming from Kerry Holford from Berenberg.

下一個問題來自 Berenberg 的 Kerry Holford。

Two questions, please. As you have mirikizumab. Can you provide any more detail on the specific issue the FDA has in manufacturing that when you expect to refile whether you would anticipate a Class 1 or 2 responders and indeed whether you do expect to launch in the U.S. this year. Secondly, a question for Anat on prioritization. So you've announced 2 divestments here in quick succession. Just interested to see, is there anything specifically driving this? Are there any additional noncore assets that you're seeking to monetize? And then as you see tirzepatide is out there, what are your priorities for the use of cash? Clearly expecting to say internal R&D investments. But I'm wondering, too, if we can expect any more external R&D investment.

請教兩個問題。因為你有 mirikizumab。你能否提供更多關於 FDA 在製造方面的具體問題的更多細節，當你希望重新提交時，你是否會預期 1 級或 2 級響應者，以及你是否確實希望今年在美國推出。其次，Anat 有一個關於優先順序的問題。所以你在這裡連續宣布了兩次撤資。只是想看看，有什麼特別的驅動力嗎？您是否有任何其他非核心資產正在尋求貨幣化？然後當你看到 tirzepatide 在那裡時，你使用現金的優先事項是什麼？顯然期望說內部研發投資。但我也想知道，我們是否可以期待更多的外部研發投資。

Thanks, Kerry. Maybe in the interest of time, since we have just a couple of minutes, let's focus on the first question, and we can connect with IR on the second questions afterwards. So mirikizumab update, I hand over to Patrik for that.

謝謝，克里。也許是為了節省時間，因為我們只有幾分鐘的時間，讓我們專注於第一個問題，然後我們可以在第二個問題上與 IR 聯繫。所以 mirikizumab 更新，我將其交給 Patrik。

Thank you very much, Kerry. As Dan stated earlier, the CRL did not cite their concerns in regards to the clinical profile of miri, but only certain aspects of the proposed commercial manufacturing process. And generally, we don't disclose the details about timing of our interactions with the FDA. But I can say that we are working very closely together with the FDA today to address the questions and also discussing the details of the next steps to understand the time line. But we remain very confident to launch miri as first-in-class in ulcerative colitis also in the U.S. In the meantime, I'm extremely happy with the launch of the approval in Japan and a positive opinion by the European regulatory body. And we are looking forward to launches outside the U.S. as early as late Q2.

非常感謝你，克里。正如 Dan 之前所說，CRL 沒有提到他們對 miri 臨床概況的擔憂，而只是提到了擬議的商業製造過程的某些方面。通常，我們不會透露我們與 FDA 互動的時間細節。但我可以說，我們今天正在與 FDA 密切合作，以解決這些問題，並討論下一步的細節，以了解時間表。但我們仍然非常有信心在美國推出 miri 作為潰瘍性結腸炎的一流藥物。與此同時，我對日本的批准和歐洲監管機構的積極意見感到非常高興。我們期待最早在第二季度末在美國以外推出。

Thank you very much, Patrik. Paul, maybe time for 1 last question, so maybe send through the last -- 1 last question from the queue.

非常感謝，帕特里克。保羅，也許是最後一個問題的時間，所以也許可以發送隊列中的最後一個問題。

The last question is coming from Mohit Bansal from Wells Fargo.

最後一個問題來自富國銀行的 Mohit Bansal。

Congrats, again. Just a question on long-term capacity for Mounjaro. I know you are trying to thinking about doubling this year, but longer term, you have talked about double of Trulicity. If you look at consensus numbers or what Street is projecting, even that may not be enough. So how are you thinking about increasing the capacity in the longer term for Mounjaro?

恭喜，再次。只是關於 Mounjaro 的長期容量的問題。我知道你正在考慮今年翻倍，但從長遠來看，你已經談到了 Trulicity 的翻倍。如果您查看共識數字或 Street 的預測，即使這樣可能還不夠。那麼，從長遠來看，您如何考慮增加 Mounjaro 的產能？

Thanks, Mohit. I'll hand it to Dave for that question, and then we'll round out.

謝謝，莫希特。我會把這個問題交給戴夫，然後我們就結束了。

Okay. I'll go right to wrap-up after that. Thanks for the question. Obviously, key. Right now, we have the unique situation of having a product so useful, we can't make enough of it really. And I think when we expand the label, it will continue to put pressure on that. I suspect this whole category will have supply pressure for some time. We're basically in an all-of-the-above moment here in terms of investing in capacity and thinking of alternative ways to expand use and make this -- fulfill the need that's out there.

好的。在那之後我會馬上結束。謝謝你的問題。顯然，關鍵。現在，我們擁有如此有用的產品的獨特情況，我們真的無法充分利用它。我認為當我們擴大標籤時，它會繼續對其施加壓力。我懷疑整個類別將在一段時間內面臨供應壓力。就投資能力和思考擴大使用並實現這一目標的替代方法而言，我們基本上處於上述所有時刻 - 滿足那裡的需求。

So we've made certain announcements we've talked about the RTP site this year. Our sister site in North Carolina, really the following year beginning to produce, that's of equivalent size. We've also made additional capacity investments in the original RTP site, which will expand the numbers further. And then today, we're talking about other delivery systems that could be providing even more capacity available for global demand fulfillment. So we're on a road map here that we're excited about in the endpoint. I think we'll probably all be a little more frustrated and impatient in the short term with the rate of expansion.

因此，我們今年發布了一些關於 RTP 網站的公告。我們在北卡羅來納州的姊妹網站，真正在次年開始生產，大小相當。我們還對原始 RTP 站點進行了額外的容量投資，這將進一步擴大數量。然後今天，我們談論的是其他交付系統，這些系統可以為全球需求滿足提供更多的可用容量。所以我們在這裡的路線圖上讓我們對端點感到興奮。我認為短期內我們可能都會對擴張速度感到更加沮喪和不耐煩。

But rest assured, the line is going up into the right at a pretty steep angle in terms of our volume and output, and we expect that to continue for several years to come. So working hard on this problem, happy with the progress, need to make more progress, and we've got plans to do that from here.

但請放心，就我們的數量和產量而言，這條線正以一個相當陡峭的角度向右上升，我們預計這種情況將持續數年。所以努力解決這個問題，對進展感到滿意，需要取得更多進展，我們已經計劃從這裡開始。

I'll also just close that comment by just punctuating a little bit the importance of the orforglipron program in terms of meeting -- fully meeting the demand that could be something like hundreds of millions of patients per year, oral solid. We know the globe has massive capacity. It's cheaper and easier to make, and that product has a lot of promise clinically but also significant profits in terms of addressing needs, particularly middle-income markets in China and other very large opportunities.

我也將通過稍微強調一下 orforglipron 計劃在會議方面的重要性來結束評論——完全滿足每年可能有數億患者的需求，口服固體。我們知道地球擁有巨大的容量。它更便宜、更容易製造，而且該產品在臨床上有很大的希望，但在滿足需求方面也有可觀的利潤，特別是中國的中等收入市場和其他非常大的機會。

And with that, let me close the call today, and thank you all for participating in this earnings call once again and your interest in Lilly and what we're doing. It's been an eventful and productive start to 2023, and we -- as we execute on our innovation rate strategy and bring all these new medicines to patients. I want to thank you again for dialing in. And please follow up with the IR team. I know we didn't get all the questions today. And if you have additional questions, please give them a call today. Have a great one, and we'll talk again soon. Thanks.

就此，讓我結束今天的電話會議，感謝大家再次參加本次財報電話會議，感謝大家對禮來公司的關注以及我們正在做的事情。到 2023 年，這是一個多事且富有成效的開端，我們——在執行我們的創新率戰略並將所有這些新藥帶給患者時。再次感謝您的撥入。請跟進 IR 團隊。我知道我們今天沒有回答所有問題。如果您還有其他問題，請立即致電他們。祝你玩得開心，我們很快會再談。謝謝。

Ladies and gentlemen, this does conclude our conference for today. This conference will be made available for replay beginning at 1:00 p.m. today running through May 11 at midnight. You may access the replay system at any time by dialing (800) 332-6854 and entering the access code, 802917. International dialers can dial (973) 528-0005. Thank you for your participation. You may now disconnect your lines.

女士們，先生們，今天的會議到此結束。該會議將從下午 1:00 開始進行重播。今天一直持續到 5 月 11 日午夜。您可以隨時撥打 (800) 332-6854 並輸入接入碼 802917 訪問重播系統。國際撥號器可以撥打 (973) 528-0005。感謝您的參與。您現在可以斷開線路。