禮來公司 (LLY) 2024 Q1 法說會逐字稿

Ladies and gentlemen, thank you for standing by, and welcome to the Lilly Q1 2024 Earnings Call. (Operator Instructions)

女士們先生們，感謝你們的支持，歡迎參加禮來公司 2024 年第一季財報電話會議。 （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.

現在我想將會議交給東道主投資者關係高級副總裁喬·弗萊徹 (Joe Fletcher)。請繼續。

Thank you, Paul, and good morning, everyone. Thank you for joining us for Eli Lilly and Company's Q1 2024 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 Officer and President of Lilly Immunology; Anne White, President of Lilly Neuroscience; Ilya Yuffa, President of Lilly International; Jake Van Naarden, President of Loxo at Lilly; and Patrik Jonsson, President of Lilly Diabetes and Obesity and Lilly U.S.A. We're also joined by Michaela Irons, Mike Springnether and Lauren Zierki of the IR team.

謝謝你，保羅，大家早安。感謝您參加禮來公司 2024 年第一季財報電話會議。我是喬‧弗萊徹，投資人關係資深副總裁。與我一起參加今天電話會議的還有禮來公司 (Lilly) 董事長兼執行長 Dave Ricks；阿納特‧阿什肯納齊 (Anat Ashkenazi)，財務長； Dan Skovronsky 博士，禮來免疫學首席科學官兼總裁； Anne White，禮來神經科學公司總裁；伊利亞‧尤法 (Ilya Yuffa)，禮來國際公司總裁； Jake Van Naarden，禮來公司 Loxo 總裁；禮來糖尿病和肥胖部總裁帕特里克·瓊森 (Patrik Jonsson) 以及禮來美國 (Lilly U.S.A.) 總裁。

During this conference call, we anticipate making projections and forward-looking statements based on our current expectations. Actual results could differ materially due to several factors, including those listed on Slide 2. 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 SEC.

在本次電話會議中，我們預計將根據目前的預期做出預測和前瞻性陳述。由於多種因素（包括投影片2 中列出的因素），實際結果可能會存在重大差異。 SEC 提交的文件中。

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

我們提供有關我們的產品和管道的資訊是為了投資界的利益。它的目的不是為了促銷，也不足以做出決策。請注意，當我們轉向準備好的評論時，我們的評論將重點放在我們的非公認會計準則財務指標。

Now I'll turn the call over to Dave.

現在我將把電話轉給戴夫。

Okay. Thanks, Joe. We're pleased with our Q1 results and the continued momentum in our business, which positions us well for accelerated growth as this year progresses. Our focus is to bring innovative medicines to people in need. And in 2024, we're investing in our people, our launches, expanding our pipeline of new medicines, including through business development, and of course, accelerating the needed capacity in our manufacturing network. Results this quarter represent a continuation of the strong growth we delivered in 2023.

好的。謝謝，喬。我們對第一季的業績和業務的持續成長勢頭感到滿意，這為我們在今年的加速成長奠定了良好的基礎。我們的重點是將創新藥物帶給有需要的人。到 2024 年，我們將投資於我們的員工、我們的產品發布、擴大我們的新藥管道，包括透過業務發展，當然還有加快我們製造網路所需的產能。本季的業績延續了我們在 2023 年實現的強勁成長。

On Slide 4, you can see details of the financial performance and progress related to our strategic deliverables. Revenue grew 26% in Q1 with our new products growing nearly $1.8 billion compared with the same period last year. We achieved several key pipeline milestones, including the positive Phase III results for tirzepatide in moderate to severe obstructive sleep apnea, the approval of our multi-dose KwikPen delivery device for Mounjaro in Europe, submission of mirikizumab in the U.S. and in the EU for moderately to severely active Crohn's disease, the resubmission of lebrikizumab in the U.S. for moderate to severe atopic dermatitis and the initiation of our Phase III study for lepodisiran, evaluating efficacy and reducing cardiovascular risk.

在投影片 4 上，您可以看到與我們的策略交付成果相關的財務表現和進度的詳細資訊。第一季營收成長 26%，新產品與去年同期相比成長近 18 億美元。我們實現了幾個關鍵的管道里程碑，包括替澤帕肽治療中度至重度阻塞性睡眠呼吸中止症的III 期臨床試驗取得積極成果、我們用於Mounjaro 的多劑量KwikPen 輸送裝置在歐洲獲得批准、在美國和歐盟提交了mirikizumab 用於中度至重度阻塞性睡眠呼吸中止症的治療。 ，評估療效並降低心血管風險。

Lilly's top priority is to ensure we execute on our ambitious manufacturing expansion agenda. We recently signed an agreement to acquire an injectable medicine facility from Nexus Pharmaceuticals in Pleasant Prairie, Wisconsin. This state-of-the-art facility has been FDA approved, and we are targeting to initiate production at the end of 2025. We broke ground earlier this month on our previously announced parenteral manufacturing site in Germany. And in existing facilities, we are working to maximize output and productivity to meet demand.

禮來公司的首要任務是確保我們執行雄心勃勃的製造擴張議程。我們最近簽署了一項協議，收購 Nexus Pharmaceuticals 位於威斯康辛州 Pleasant Prairie 的注射藥品設施。這個最先進的工廠已獲得 FDA 批准，我們的目標是在 2025 年底開始生產。在現有設施中，我們正在努力最大限度地提高產量和生產力以滿足需求。

The recent EMA approval and upcoming launch of our multi-dose KwikPen delivery life for Mounjaro will unlock new supply capacity for Europe and other international markets. While we are also seeing meaningful progress in the ramp of new lines in existing Lilly and CDMO sites for the United States.

最近 EMA 的批准以及即將推出的 Mounjaro 多劑量 KwikPen 交貨壽命將為歐洲和其他國際市場釋放新的供應能力。同時，我們也看到美國現有禮來公司和 CDMO 基地的新生產線建設取得了有意義的進展。

We continue to make progress against our plans to increase manufacturing capacity, the most ambitious expansion plan in our company's history. Lastly, we distributed over $1 billion in dividends during the first quarter.

我們繼續在提高製造能力的計劃上取得進展，這是我們公司歷史上最雄心勃勃的擴張計劃。最後，我們在第一季分配了超過 10 億美元的股息。

On Slide 5, you'll see a list of the key events since our Q4 earnings call, including the milestones I mentioned earlier and several other important updates.

在投影片 5 上，您將看到自第四季度財報電話會議以來的關鍵事件列表，包括我之前提到的里程碑和其他幾個重要更新。

So now let me turn the call over to Anat to review our Q1 financial results.

現在讓我將電話轉給 Anat，回顧我們第一季的財務表現。

Thanks, Dave. Slide 6 summarizes financial performance in the first quarter of 2024. First quarter revenue growth of 26% was driven by new products, primarily Mounjaro and Zepbound. Gross margin as a percent of revenue increased from 78.4% in Q1 2023 to 82.5% in Q1 2024. Gross margin in the quarter benefited from higher realized prices, variable product mix and, to a lesser extent, improved production costs.

謝謝，戴夫。投影片 6 總結了 2024 年第一季的財務表現。毛利率佔收入的百分比從2023 年第一季的78.4% 上升至2024 年第一季的82.5%。 ）。

Marketing, selling and administrative expenses increased 12% primarily driven by promotional efforts supporting current and future launches as well as increased compensation and benefit costs. R&D expenses increased 27%, driven by higher development expenses for late-stage assets and additional investments in early-stage research as well as a onetime charge of approximately $75 million associated with the termination of the Verzenio prostate program.

行銷、銷售和管理費用增加了 12%，主要是由於支援當前和未來發布的促銷活動以及薪酬和福利成本的增加。研發費用增加了 27%，這是由於後期資產的開發費用增加、早期研究的額外投資以及與終止 Verzenio 前列腺項目相關的約 7500 萬美元的一次性費用所致。

In Q1, we recognized acquired IPR&D charge of $111 million, which negatively impacted EPS by $0.10. Operating income increased 63% in Q1 driven by higher revenue from new products, partially offset by operating expense growth. Our Q1 effective tax rate was 11.9% compared to 12.8% in Q1 2023 driven by a larger net discrete tax benefit reflected in Q1 2024 compared with the same period in 2023. We delivered earnings per share of $2.58 in Q1, a 59% increase compared to Q1 2023, inclusive of the negative impact of $0.10 from acquired IPR&D charges in both periods.

第一季度，我們確認收購的智慧財產權與研發費用為 1.11 億美元，這對每股盈餘產生了 0.10 美元的負面影響。由於新產品收入增加，第一季營業收入成長了 63%，但部分被營業費用成長所抵銷。我們第一季的有效稅率為11.9%，而2023 年第一季為12.8%，這是由於2024 年第一季反映的淨離散稅收優惠與2023 年同期相比更大。股收益為2.58 美元，比2023 年第一季增長了59%到 2023 年第一季度，包括這兩個時期收購的 IPR&D 費用 0.10 美元的負面影響。

On Slide 7, we quantify the effect of price, rate and volume on revenue growth. U.S. revenue increased 28% in Q1 driven by growth of Mounjaro, Zepbound and Verzenio. Unprecedented demand for our incretin medicines led to wholesaler backorders of Trulicity, Mounjaro and Zepbound at quarter end. Realized prices in the U.S. increased 16%, largely driven by Mounjaro access and savings card dynamics.

在投影片 7 中，我們量化了價格、費率和數量對收入成長的影響。在 Mounjaro、Zepbound 和 Verzenio 成長的推動下，第一季美國營收成長了 28%。對我們的腸促胰島素藥物前所未有的需求導致 Trulicity、Mounjaro 和 Zepbound 的批發商在季度末缺貨。美國的實際價格上漲了 16%，這主要是受到 Mounjaro 准入和儲蓄卡動態的推動。

Moving to Europe. Revenue growth was once again strong, increasing 29% in constant currency, driven primarily by volume from Verzenio and Mounjaro as well as payments associated with the distribution and divestiture agreements.

搬到歐洲。營收成長再次強勁，以固定匯率計算成長了 29%，這主要是由 Verzenio 和 Mounjaro 的銷量以及與分銷和剝離協議相關的付款推動的。

Japan revenue grew 2% in constant currency. Volume growth of 7% was driven by Mounjaro and Verzenio, partially offset by decreased volume for Trulicity and a partnership milestone in the base period. Price declined 5% in the quarter.

以固定匯率計算，日本營收成長 2%。 Mounjaro 和 Verzenio 推動了 7% 的銷售成長，部分被 Trulicity 銷量下降和基期合作里程碑所抵消。本季價格下跌 5%。

Moving to China. Q1 revenue increased 4% in constant currency. Volume growth was driven by Tyvyt, partially offset by Olumiant and Cialis.

搬到中國。以固定匯率計算，第一季營收成長 4%。銷售成長由 Tyvyt 推動，但被 Olumiant 和 Cialis 部分抵消。

Revenue in the Rest of the World increased 31% in constant currency, primarily driven by volume growth from Mounjaro and to a lesser extent, Verzenio and Jardiance.

以固定匯率計算，世界其他地區的收入成長了 31%，這主要是受到 Mounjaro 以及較小程度 Verzenio 和 Jardiance 銷量成長的推動。

Slide 8 provides additional perspective across our product categories. First, I would like to highlight Verzenio, which saw worldwide sales increased 40% in Q1, driven by continued volume growth in the early breast cancer indication. Jaypirca revenue increased to $50 million worldwide, representing an acceleration in sequential quarterly growth following the December 2023 approval for the CLL indication. We're looking forward to potentially making this medicine available to even more patients as future Phase III trials read out.

幻燈片 8 提供了我們產品類別的更多視角。首先，我想強調 Verzenio，在早期乳癌適應症的銷售持續成長的推動下，該公司第一季的全球銷售額成長了 40%。 Jaypirca 在全球範圍內的收入增至 5000 萬美元，表明自 2023 年 12 月 CLL 適應症獲得批准後，季度環比增長加速。我們期待隨著未來的 III 期試驗的結果，有可能讓更多的患者使用這種藥物。

Next in Q1, Mounjaro sales were $1.8 billion globally, and $1.5 billion in the U.S., up from $568 million and $536 million in Q1 2023, respectively. Sequential quarter-over-quarter revenue for Mounjaro in the U.S. was impacted by a onetime benefit from changes in estimates for rebates and discounts in Q4 2023 as well as lower inventory in the channel in Q4 2024 and a strong demand. Access level across commercial and Part D were consistent with high levels we communicated on our last earnings call and near parity with established injectable incretin medicines.

接下來第一季度，Mounjaro 在全球的銷售額為 18 億美元，在美國的銷售額為 15 億美元，而 2023 年第一季的銷售額分別為 5.68 億美元和 5.36 億美元。 Mounjaro 在美國的環比收入受到 2023 年第四季回扣和折扣預估變化帶來的一次性收益以及 2024 年第四季通路庫存減少和強勁需求的影響。商業和 D 部分的准入水平與我們在上次財報電話會議上傳達的高水平一致，並且與現有的注射腸促胰島素藥物接近相同。

The demand for tirzepatide is very strong. And each week, hundreds of thousands of people fill scripts from Mounjaro and Zepbound. Yet we understand the frustration from those facing prescription delays or uncertainties yet in their medicine. While we are working tirelessly to ramp supply and expect meaningful increases in shipment volumes in the second half of the year, demand continues to outstrip even increased supply. We remain on track to meet expectations we set earlier this year, the production of saleable doses of incretin medicine in the second half of 2024 will be at least 1.5x the saleable doses in the second half of 2023. In the short to midterm, we expect sales growth to primarily be a function of the quantities we can produce and ship.

對替西帕肽的需求非常強勁。每週都有數十萬人填寫來自 Mounjaro 和 Zepbound 的腳本。然而，我們理解那些面臨處方延誤或藥物不確定性的人的沮喪。雖然我們正在不懈地努力增加供應，並預計下半年出貨量將大幅增加，但需求仍超過供應的成長。我們仍有望實現今年稍早設定的預期，2024 年下半年腸促胰島素藥物的可銷售劑量產量將至少是 2023 年下半年可銷售劑量的 1.5 倍。取決於我們可以生產和運輸的數量。

Outside the U.S., we're delighted that the multi-dose KwikPen delivery device from Mounjaro was recently approved in the EU, adding to the U.K. approval earlier this year. This approval applies to both type 2 diabetes and chronic weight management indication as they are under the single brand in Europe. While timing for launch will vary by country, we expect to start launching in the EU in coming weeks.

在美國以外，我們很高興 Mounjaro 的多劑量 KwikPen 輸送裝置最近在歐盟獲得批准，英國今年稍早也獲得了批准。該批准適用於第 2 型糖尿病和慢性體重管理適應症，因為它們在歐洲屬於單一品牌。雖然發佈時間因國家而異，但我們預計將在未來幾週內開始在歐盟推出。

In Q1, worldwide Trulicity revenue declined 26%. U.S. Trulicity revenue decreased 30% driven by lower volume, primarily due to supply constraints and competitive dynamics. In addition, sales in international markets were impacted by measures we have taken to minimize disruption to existing patients, including communicating to health care professionals to not start new patients on Trulicity.

第一季度，Trulicity 全球營收下降了 26%。由於供應限制和競爭動態，銷售下降導緻美國 Trulicity 收入下降 30%。此外，我們為盡量減少對現有患者的干擾而採取的措施影響了國際市場的銷售，包括與醫療保健專業人員溝通不要讓新患者開始使用 Trulicity。

Turning to Slide 9. We have seen exceptionally strong U.S. launch progress for Zepbound with over $0.5 billion in sales in Q1. We're rapidly building out access for Zepbound in the U.S. And as of April 1, we have approximately 67% access in the commercial segment. As a reminder, patients' access to this market is a two-step process typically require individual employers to opt in to an anti-obesity medicine rider following PBM coverage. We are continuing to focus on broadening access, both with PBMs and for employer opt-ins and early progress is encouraging.

轉向幻燈片 9。我們正在美國快速建立 Zepbound 的存取權限。提醒一下，患者進入這個市場需要兩個步驟，通常需要個別雇主在 PBM 承保後選擇加入抗肥胖藥物附加險。我們將繼續致力於透過 PBM 和雇主選擇擴大准入，早期進展令人鼓舞。

On Slide 10, we provide an update on capital allocation.

在投影片 10 中，我們提供了資本配置的最新情況。

Slide 11 shows updated 2024 financial guidance. Given the strength we're seeing in our business and projections for continued acceleration expected in the second half of the year, we're increasing our full year revenue outlook by $2 billion on the top and bottom end of the range to be between $42.4 billion to $43.6 billion. This increase is primarily due to the strong performance of Mounjaro and Zepbound and greater visibility and confidence into our production expansion for the remainder of 2024. With this update, year-over-year revenue growth of the company is now expected to be approximately 26% at the midpoint or approximately 35% for the core business, which excludes the impact from global divestitures.

投影片 11 顯示了更新的 2024 年財務指引。鑑於我們看到的業務實力以及預計下半年將繼續加速成長，我們將全年營收預期上調 20 億美元，將區間的上限和下限提高到 424 億美元之間至 436 億美元。這一成長主要歸功於 Mounjaro 和 Zepbound 的強勁表​​現，以及我們對 2024 年剩餘時間生產擴張的可見性和信心。 %，其中不包括全球資產剝離的影響。

Given the update to revenue guidance, we now expect the ratio of gross margin less OpEx divided by revenue to be in the range of 32% to 34% on a reported basis and 33% to 35% on a non-GAAP basis, representing further margin expansion. We're reaffirming guidance for other income and expense and tax rate, which now takes into consideration Q1 results.

鑑於收入指引的更新，我們現在預計毛利率減去營運支出除以收入的比率在報告基礎上將在32% 至34% 之間，在非GAAP 基礎上將在33% 至35% 之間，這意味著進一步利潤擴張。我們重申其他收入和支出以及稅率的指導，現在考慮了第一季的業績。

Based on these updates, and inclusive of Q1 IPR&D charges of $0.10 per share, we now expect EPS to be in the range of $13.05 to $13.55 on a reported basis and $13.50 to $14 on a non-GAAP basis.

根據這些更新，並包括第一季每股 0.10 美元的 IPR&D 費用，我們現在預計每股收益將在 13.05 美元至 13.55 美元之間，按非 GAAP 計算將在 13.50 美元至 14 美元之間。

Now I'll turn the call over to Dan to highlight progress in R&D.

現在我將把電話轉給 Dan，以強調研發方面的進展。

Thanks, Anat. Let me start with our exciting announcement from earlier this month. That was the positive Phase III results from the SURMOUNT-OSA studies, which evaluated tirzepatide for treatment of adults with obesities and moderate to severe obstructive sleep apnea known as OSA. OSA is a sleep-related breathing disorder characterized by complete or partial collapse of the upper airway during sleep. OSA can have serious cardiometabolic complications contributing to hypertension, coronary heart disease, stroke, heart failure, atrial fibrillation and even type 2 diabetes.

謝謝，阿納特。讓我從本月初我們令人興奮的公告開始。這是 SURMOUNT-OSA 研究的第三階段積極結果，該研究評估了替西帕肽治療成人肥胖症和中度至重度阻塞性睡眠呼吸中止症（OSA）的效果。 OSA 是一種與睡眠相關的呼吸障礙，其特徵是睡眠期間上呼吸道完全或部分塌陷。 OSA 可能會產生嚴重的心臟代謝併發症，導致高血壓、冠狀動脈心臟病、中風、心臟衰竭、心房顫動甚至第 2 型糖尿病。

The need is significant. OSA impacts 80 million people in the U.S. with more than 20 million people suffering from moderate to severe OSA. We also know that a substantial majority, approximately 70% of people with OSA also live with obesity. While there are pharmaceutical treatments for the excessive daytime sleepiness associated with OSA, tirzepatide could potentially be the first pharmacological treatment for the underlying disease.

需求是巨大的。 OSA 影響美國 8000 萬人，其中超過 2000 萬人患有中度至重度 OSA。我們也知道，絕大多數（約 70%）患有 OSA 的人也患有肥胖症。雖然有藥物治療與 OSA 相關的白天過度嗜睡，但替西帕肽可能是潛在疾病的第一種藥物治療。

As shown on Slide 12, SURMOUNT-OSA was comprised of two separate trials run under one master protocol. Study 1 evaluated tirzepatide in participants not currently on positive airway pressure or PAP therapy, while Study 2 evaluates tirzepatide in patients who had used PAP for at least 3 months prior to the study and plans to continue PAP therapy during the entire course of the trial. A total of 469 participants were enrolled across these studies. Each study randomized participants to either maximum tolerated dose approved for tirzepatide, which can be 10 milligrams or 15 milligrams, or to placebo. And patients were followed on therapy for 52 weeks.

如投影片 12 所示，SURMOUNT-OSA 由兩個在一個主方案下執行的獨立試驗組成。研究1評估了目前未接受氣道正壓通氣或PAP治療的受試者的替澤帕肽，而研究2評估了在研究前已使用PAP至少3個月併計劃在整個試驗過程中繼續PAP治療的患者的替澤帕肽。這些研究總共招募了 469 名參與者。每項研究將參與者隨機分配到經批准的替西帕肽最大耐受劑量（可以是 10 毫克或 15 毫克）或安慰劑。患者接受為期 52 週的治療追蹤。

On Slide 13, we show the results of Study 1. For the efficacy estimate on mean Apnea-Hypopnea Index, or AHI, tirzepatide led to a mean reduction of 27.4 events per hour compared to a mean AHI reduction of 4.8 events per hour for placebo. This difference was highly statistically significant. AHI baseline values were 52.9 and AHI was reduced by 55% in the tirzepatide arm. We also saw a mean body rate reduction of 18.1% for tirzepatide treatment consistent with our expectations for the study. This was, of course, also statistically significant versus placebo.

在投影片13 中，我們展示了研究1 的結果。次事件。這種差異具有高度統計顯著性。替澤帕肽組的 AHI 基線值為 52.9，AHI 降低了 55%。我們還發現替西帕肽治療的平均身體率降低了 18.1%，這與我們對這項研究的預期一致。當然，與安慰劑相比，這也具有統計意義。

On Slide 14, we show the results of Study 2. In this population, for the efficacy [estimand], tirzepatide led to a mean AHI reduction of 30.4 events per hour compared to a mean AHI reduction of 6.0 events per hour for placebo. The baseline AHI was 46.1% in the tirzepatide arm and mean AHI reduction was 62.8%. Again, we saw impressive weight loss with a mean body rate reduction of 20.1% from baseline. These results were also all highly statistically significant.

在投影片14 上，我們展示了研究2 的結果。次。替澤帕肽組的基線 AHI 為 46.1%，平均 AHI 降低為 62.8%。我們再次看到令人印象深刻的體重減輕，平均體重比基線降低了 20.1%。這些結果也都具有高度統計顯著性。

In both studies, the overall safety profile was similar to previously reported SURMOUNT and SURPASS trials. The most commonly reported adverse events were gastrointestinal-related and generally mild to moderate in severity, with the most commonly reported gastrointestinal adverse events for patients treated with tirzepatide being diarrhea, nausea, vomiting and constipation.

在這兩項研究中，整體安全性與先前已通報的 SURMOUNT 和 SURPASS 試驗相似。最常見的不良事件是胃腸道相關的，嚴重程度一般為輕度至中度，接受替西帕肽治療的患者最常見的胃腸道不良事件是腹瀉、噁心、嘔吐和便秘。

Prior to the study readout, we noted investor questions about what level of weight loss we would see given several factors that were uniquely combined in the study of tirzepatide. First, the primary aim of the study was not treatment of obesity. Second, that the population was approximately 70% males, in whom weight loss can be harder to achieve with incretin medicines. Third, there's a particularly high baseline BMI in this population. And finally, the use of the 10- or 15-milligram maximum tolerated dose approach. We were therefore highly reassured to see weight loss observed across the two studies at 52 weeks was nearly 20% despite this difficult-to-treat population.

在研究結果公佈之前，我們注意到投資者提出的問題，即考慮到替澤帕肽研究中獨特結合的幾個因素，我們會看到什麼程度的體重減輕。首先，研究的主要目的不是治療肥胖。其次，該族群中約 70% 是男性，使用腸促胰島素藥物可能更難實現減重。第三，這個族群的基線體重指數特別高。最後，使用 10 或 15 毫克最大耐受劑量方法。因此，我們非常放心地看到這兩項研究在 52 週時觀察到的體重減輕了近 20%，儘管這是一個難以治療的人。

Consistent with other Phase III studies of tirzepatide at the 52-week time point, we did not see weight loss plateau. We'll present detailed results of SURMOUNT-OSA during a symposium at ADA on June 21. Additionally, we plan to submit to the FDA and other global regulatory agencies beginning midyear.

與 52 週時間點的替澤帕肽的其他 III 期研究一致，我們沒有看到體重減輕平台期。我們將在 6 月 21 日舉行的 ADA 研討會上展示 SURMOUNT-OSA 的詳細結果。

Moving to the other updates across our portfolio. Slide 15 shows select pipeline opportunities as of April 26, and Slide 16 shows potential key events for the year. We're pleased to share that results were positive in QWINT-4, the first Phase III study of insulin efsitora alfa, our once-weekly basal insulin. This study evaluated efsitora compared to insulin glargine in adult participants with type 2 diabetes who are on multiple daily insulin injections. In the coming weeks, we expect to report top line results from QWINT-4 as well as QWINT T-2 which is evaluating efsitora compared to degludec in adults with type 2 diabetes who are naive to basal insulin.

轉向我們產品組合中的其他更新。幻燈片 15 顯示了截至 4 月 26 日的精選管道機會，幻燈片 16 顯示了今年潛在的關鍵事件。我們很高興地與大家分享，QWINT-4 的結果是正面的，QWINT-4 是我們每週一次的基礎胰島素 efsitora alfa 的第一個 III 期研究。這項研究在每日多次注射胰島素的 2 型糖尿病成年參與者中評估了 efsitora 與甘精胰島素的比較。在接下來的幾週內，我們預計將報告 QWINT-4 和 QWINT T-2 的主要結果，該結果正在評估 efsitora 與德谷胰島素在未接受過基礎胰島素的成人 2 型糖尿病患者中的比較。

Together, these are the first 2 of 5 studies in the efsitora Phase III program.

這些是 efsitora III 期項目 5 項研究中的前 2 項。

Additional updates in our late-stage diabetes and obesity pipeline include results of the EMPACT-MI study, showing Jardiance had a 10% relative risk reduction in the primary composite endpoint of time-to-first hospitalization due to heart failure or all-cause mortality versus placebo, which did not reach statistical significance.

我們晚期糖尿病和肥胖管道的其他更新包括 EMPACT-MI 研究的結果，顯示 Jardiance 在心臟衰竭或全因死亡率而首次住院時間的主要複合終點方面相對風險降低了 10%與安慰劑相比，未達到統計顯著性。

We've completed enrollment for SURMOUNT-MMO with over 15,000 participants, and for both orforglipron studies in chronic weight management, ATTAIN-1 and ATTAIN-2, which together enrolled 4,500 participants.

我們已經完成了 SURMOUNT-MMO 的招募，共有超過 15,000 名參與者，以及慢性體重管理的 orforglipron 研究 ATTAIN-1 和 ATTAIN-2，總共招募了 4,500 名參與者。

Finally, we've now initiated the [TRANSCEND] Phase III program studying retatrutide in type 2 diabetes.

最後，我們現在啟動了研究瑞他魯肽治療第 2 型糖尿病的 [TRANSCEND] III 期計畫。

In the cardiovascular disease area, we're excited to have initiated the Phase III trial for lepodisiran, the subcutaneous injectable siRNA. This study will evaluate the efficacy in improving cardiovascular outcomes for participants with high lipoprotein A, who have cardiovascular disease or at a risk of heart attack or stroke. We are evaluating the efficacy of lepodisiran in both secondary and high-risk primary prevention. And we hope this will one day offer health care providers a treatment option for a broad group of patients at increased cardiovascular risk due to high LP(a) levels.

在心血管疾病領域，我們很高興啟動了皮下注射 siRNA lepodisiran 的 III 期試驗。這項研究將評估改善患有心血管疾病或有心臟病或中風風險的高脂蛋白 A 參與者的心血管結果的功效。我們正在評估 Lepodisiran 在二級和高風險一級預防中的功效。我們希望有一天，這將為醫療保健提供者提供一種治療選擇，為廣大因 LP(a) 水平高而導致心血管風險增加的患者提供治療選擇。

Earlier in our diabetes and obesity pipeline, we've now initiated a Phase II monotherapy study evaluating eloralintide, our selective amylin receptor agonist in obesity.

在我們的糖尿病和肥胖管道的早期，我們現在啟動了一項 II 期單一療法研究，評估 eloralintide，我們的選擇性胰淀素受體激動劑治療肥胖症。

Turning to oncology. We made the decision to terminate for futility, the Phase III CYCLONE 3 trial evaluating Verzenio in metastatic hormone-sensitive prostate cancer following an interim analysis. This concludes development of Verzenio in prostate cancer following last quarter's announcement that the CYCLONE 2 study did not meet its primary endpoint.

轉向腫瘤學。經過中期分析，我們決定終止評估 Verzenio 治療轉移性荷爾蒙敏感前列腺癌的 III 期 CYCLONE 3 試驗，但結果無效。繼上個季度宣布 CYCLONE 2 研究未達到其主要終點後，Verzenio 在前列腺癌方面的開發就此結束。

In early oncology development, we've initiated Phase I trials for two new assets. The first is our Nectin-4 ADC, which came from our acquisition of Emergence Therapeutics. The second is PNT2001, which came from our acquisition of POINT Biopharma. We're encouraged by what we're seeing in our oncology portfolio and expect 2024 to be particularly productive. Along with the Nectin-4 ADC and PNT2001 start, we expect at least three other new molecules to enter the clinic this year. We look forward to sharing more details with the investment community at an oncology-focused investor event hosted by the Lilly Oncology team. This event will take place on the evening of Sunday, June 2 in Chicago in conjunction with the ASCO annual meeting and will also be available via webcast. We plan to provide an update on our oncology strategy and pipeline opportunities. Additional details will be available soon regarding this event.

在早期腫瘤學開發中，我們已經啟動了兩種新資產的一期試驗。第一個是我們的 Nectin-4 ADC，它來自我們對 Emergence Therapeutics 的收購。第二個是PNT2001，它來自我們收購了POINT Biopharma。我們對腫瘤學產品組合中所看到的情況感到鼓舞，並預計 2024 年將特別有成效。隨著 Nectin-4 ADC 和 PNT2001 的啟動，我們預計今年至少有另外三種新分子進入臨床。我們期待在禮來腫瘤學團隊主辦的以腫瘤學為重點的投資者活動中與投資界分享更多細節。活動將於 6 月 2 日星期日晚上在芝加哥與 ASCO 年會同時舉行，也可透過網路直播觀看。我們計劃提供有關我們的腫瘤學策略和管道機會的最新資訊。有關此活動的更多詳細資訊將很快公佈。

Turning to Neuroscience. Last month, we announced that the FDA plans to convene a meeting of the peripheral and CNS Drugs Advisory Committee to discuss donanemab in early symptomatic Alzheimer's disease. We expect the advisory committee meeting will take place in mid-2024, but the exact date will be confirmed when it appears in the Federal Register. We expect the focus to be around the safety and efficacy profile of donanemab, along with unique aspects of the clinical program. We remain confident in donanemab's potential to offer very meaningful benefits to patients and look forward to addressing the FDA's questions in this form.

轉向神經科學。上個月，我們宣布 FDA 計劃召開一次週邊和中樞神經系統藥物諮詢委員會會議，討論多納奈單抗在早期症狀性阿茲海默症中的應用。我們預計諮詢委員會會議將於 2024 年中期舉行，但具體日期將在聯邦公報上公佈時確認。我們預計重點將圍繞多南單抗的安全性和有效性以及臨床計劃的獨特方面。我們對 donanemab 為患者提供非常有意義的益處的潛力充滿信心，並期待以這種形式解決 FDA 的問題。

Additionally, we made the decision to discontinue investigation of GBA1, our gene therapy assets in Gaucher disease type 2. Phase II studies in Parkinson's disease and Gaucher disease type 1 are still underway and have not been impacted by this decision.

此外，我們決定停止對GBA1 的研究，GBA1 是我們針對2 型戈謝氏症的基因治療資產。 。

Finally, in immunology, we've submitted mirikizumab to the FDA and EMA for approval for use in adults with moderately to severely active Crohn's disease. In the U.S., we've resubmitted lebrikizumab's application to the FDA for moderate to severe atopic dermatitis. This is following a complete response letter based on inspection findings of the third-party manufacturer. As a reminder, the letter stated no concerns with the clinical data package safety or label. We expect regulatory action in the second half of this year.

最後，在免疫學方面，我們已向 FDA 和 EMA 提交了 mirikizumab，以批准用於患有中度至重度活動性克隆氏症的成年人。在美國，我們已向 FDA 重新提交了 lebrikizumab 治療中度至重度異位性皮膚炎的申請。這是根據第三方製造商的檢查結果發出的完整回覆函。作為提醒，該信函表示不擔心臨床資料包的安全性或標籤。我們預計今年下半年將採取監管行動。

We're also announcing that in the coming months, we'll be initiating Phase III studies evaluating lebrikizumab in two new indications: chronic rhinosinusitis with nasal polyposis and allergic rhinitis due to perennial allergens. Lebrikizumab will be the first biologic to be evaluated in Phase III for allergic rhinitis. We're optimistic about the potential of lebrikizumab to be an important treatment option in these patient populations as well as in atopic dermatitis. In earlier-stage immunology development, we've advanced our CD19 antibody into Phase II for multiple sclerosis.

我們也宣布，在接下來的幾個月中，我們將啟動 III 期研究，評估 lebrikizumab 的兩個新適應症：伴隨鼻息肉症的慢性鼻竇炎和常年過敏原引起的過敏性鼻炎。 Lebrikizumab 將是第一個在過敏性鼻炎 III 期中進行評估的生物製劑。我們對 lebrikizumab 成為這些患者群體以及異位性皮膚炎的重要治療選擇的潛力持樂觀態度。在早期免疫學開發中，我們已將 CD19 抗體推進到治療多發性硬化症的 II 期。

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

現在我將把電話轉回給戴夫，讓他致閉幕詞。

Okay. Thanks, Dan. Before we go to Q&A, let me briefly sum up the progress in our first quarter. Strong revenue growth in Q1 was driven by our recent product launches, primarily Mounjaro and Zepbound. We expect acceleration in revenue growth through the second half of the year as supply of incretin medicines continues to ramp. Significant advances in our pipeline include top line data from tirzepatide and SURMOUNT-OSA, approval of the KwikPen delivery device from Mounjaro in the EU, submission of mirikizumab and lebrikizumab as well as initiation of lepodisiran Phase III study, as Dan just mentioned. We are continuing to invest in recent and upcoming launches, internal and external pipeline development and our manufacturing expansion agenda. This is to sustain our long-term growth outlook.

好的。謝謝，丹。在進行問答之前，讓我先簡單總結一下我們第一季的進展。我們最近推出的產品（主要是 Mounjaro 和 Zepbound）推動了第一季營收的強勁成長。我們預計，隨著腸促胰島素藥物供應的持續增加，下半年收入成長將加速。正如 Dan 剛才提到的，我們管道中的重大進展包括來自 tirzepatide 和 SURMOUNT-OSA 的一線數據、Mounjaro 的 KwikPen 輸送裝置在歐盟的批准、mirikizumab 和 lebrikizumab 的提交以及 lepodisiran III 期研究的啟動。我們將繼續投資於最近和即將推出的產品、內部和外部管道開發以及我們的製造擴張議程。這是為了維持我們的長期成長前景。

So now let me turn the call over to Joe to moderate the Q&A session.

現在讓我把電話轉給喬來主持問答環節。

Thanks, Dave. We'd like to take questions from as many callers as possible and to conclude our call in a timely manner. (Operator Instructions)

謝謝，戴夫。我們希望回答盡可能多的來電者的問題，並及時結束我們的通話。 （操作員說明）

Paul, please provide instructions for the Q&A session, and we're ready for our first caller.

Paul，請提供問答環節的說明，我們已準備好迎接第一位來電者。

(Operator Instructions) The first question today is coming from Chris Schott from JPMorgan.

（操作員說明）今天的第一個問題來自摩根大通的 Chris Schott。

Congrats on the progress here. I just had a question, just was hoping you could elaborate a bit more on the capacity dynamics that are leading to the guidance raise today. Specifically just looking for little more color, is this more U.S. or international? And should we read this as more capacity in the system than you expected or just a faster ramp of the new plant and maybe the same overall capacity as you exit the year?

恭喜這裡的進展。我只是有一個問題，只是希望您能詳細說明導致今天指導提高的產能動態。具體來說就是尋找更多的顏色，這是更美國化還是國際化？我們是否應該將其理解為系統中的產能比您預期的要多，或者只是新工廠的產能增長更快，並且可能與您今年退出時的總體產能相同？

Thanks, Chris. I'll hand over to Anat to talk about the guidance raise.

謝謝，克里斯。我將把指導意見的加薪問題交給阿納特來討論。

Thanks for the question, Chris. And as we've mentioned earlier in the year when we issued guidance, we said that we expect capacity and supply to ramp towards the second half of the year, and that's what we're seeing.

謝謝你的提問，克里斯。正如我們在今年稍早發布指導意見時提到的那樣，我們預計下半年產能和供應量將增加，這就是我們所看到的。

Now as a reminder, we do have quite a large number of nodes across our supply chain that have to come online or ramp capacity. We are -- if you look at everything we have under construction, or ramping up, we have six sites right now between the two sites in North Carolina, a site in Ireland, two sites in Indiana, a site in Germany and then a seventh one that we just purchased, they are all either ramping up or under construction.

現在提醒一下，我們的供應鏈中確實有相當多的節點必須上線或提高產能。如果你看看我們正在建造或正在建設中的一切，我們現在有六個站點，分別是北卡羅來納州的兩個站點、愛爾蘭的一個站點、印第安納州的兩個站點、德國的一個站點，然後是第七個站點我們剛剛購買的一個，它們要么正在加緊建設，要么正在建設中。

And there are multiple nodes across that supply chain that have to become operational, which requires approval, et cetera, for three products, depending on which product runs on which line, that are planned throughout the year.

該供應鏈上有多個節點必須投入運行，這需要三種產品的批准等，具體取決於全年計劃的哪種產品在哪條生產線上運行。

Now that we're 4 months into the year, we have greater visibility into that -- into these nodes of capacity and feel more confident. Just as one example, the approval of the KwikPen in Europe that just came in slightly ahead of our expectation gives us additional confidence in our ability to launch KwikPen for patients in Europe.

現在已經進入今年 4 個月了，我們對這些能力節點有了更清晰的了解，並感到更有自信。舉個例子，KwikPen 在歐洲的批准略高於我們的預期，這讓我們對為歐洲患者推出 KwikPen 的能力更有信心。

So it is across our sites globally as well as ramping up capacity with partners or CDMOs as well as in existing sites where we're making investments to expand where we can or ramp up capacity. So it's across our supply chain.

因此，我們在全球各地的工廠以及與合作夥伴或 CDMO 一起提高產能，以及我們正在投資以擴大產能或提高產能的現有工廠。所以它貫穿我們的供應鏈。

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

下一個問題來自富國銀行的 Mohit Bansal。

I have a question regarding the pricing. So if you look at the script trend, it seems like there was a little bit of adverse relationship in the pricing versus fourth quarter. Can you comment on that? And how should we think about the cadence of price volume over the quarters for the year?

我有一個關於定價的問題。因此，如果你看一下腳本趨勢，你會發現定價與第四季度之間似乎存在一些不利關係。你能對此發表評論嗎？我們該如何看待一年中各季度的價格成交量節奏？

Thanks, Mohit. You didn't say it, but I assume you're talking about Mounjaro and Zepbound so I'll hand over to Patrik to make some commentary on net price.

謝謝，莫希特。你沒有說，但我假設你在談論 Mounjaro 和 Zepbound，所以我將交給 Patrik 對淨價做出一些評論。

Thank you very much, Mohit. When you look at the pricing of Mounjaro, I think it's important to take into account that in the Q4 earnings, we announced a onetime adjustment for Mounjaro in Q4 that was quite significant. So it was a onetime adjustment in the base of Q4.

非常感謝你，莫希特。當你查看 Mounjaro 的定價時，我認為重要的是要考慮到在第四季度的收益中，我們宣布了第四季度對 Mounjaro 的一次性調整，這是相當重大的。所以這是第四季基數的一次性調整。

When we look forward for the first half of 2024, it's important to have in mind that we also terminated the $25 saving card 6/30/2023, but patients that were on are grandfathered until 6/30/2024. So there would probably be some benefits during the first half of 2024 for Mounjaro. But from the second half of this year, we should expect to see typical pricing headwinds for Mounjaro as well.

當我們展望2024 年上半年時，重要的是要記住，我們還在2023 年6 月30 日終止了25 美元的儲蓄卡，但使用該卡的患者將在2024 年6 月30 日之前享受豁免。因此，Mounjaro 在 2024 年上半年可能會帶來一些好處。但從今年下半年開始，我們預期 Mounjaro 也會遇到典型的定價阻力。

The next question is coming from Umer Raffat from Evercore.

下一個問題來自 Evercore 的 Umer Raffat。

I wanted to focus a quick second on Part D reimbursement dynamics, if I may. And my question is, will tirzepatide be considered differently than a "weight loss drug" to secure Part D reimbursement? And the new indications like sleep apnea, will they considered an applicable drug and not get lumped up as a broad "weight loss drug"?

如果可以的話，我想快速關註一下 D 部分的報銷動態。我的問題是，為了確保 D 部分報銷，替西帕肽是否會被視為與「減肥藥」不同？而像睡眠呼吸中止症這樣的新適應症，它們會被視為一種適用的藥物，而不是被歸類為一種廣泛的「減肥藥」嗎？

Thanks, Umer. I'll go to Patrik for that question.

謝謝，烏默。我會去找派崔克詢問這個問題。

Thank you very much, Umer. I think with the announcement made by the CMS early April to reimburse comorbidities for obesity based upon the SELECT trial, we're also confident that with the new data that we presented just weeks ago in terms of obstructive sleep apnea, that's going to be reimbursed in Medicare Part D. And we expect similarly for other comorbidities and the readout of HFpEF, assuming that's positive and approved, and later on with the mobility-mortality outcome study.

非常感謝你，烏梅爾。我認為，隨著 CMS 4 月初宣布根據 SELECT 試驗報銷肥胖合併症，我們也相信，根據我們幾週前提供的有關阻塞性睡眠呼吸中止症的新數據，這筆費用將得到報銷在醫療保險D 部分中。 我們對其他合併症和HFpEF 的讀數也有類似的預期，假設這是積極的並獲得批准，然後進行流動性死亡率結果研究。

Still, our true north is really to get the true Treat and Reduce Obesity Act cost, and we strongly believe it's not a matter of if but when. We don't see it likely to pass in 2024, but there is still a small likelihood that that's going to happen.

儘管如此，我們真正的目標實際上是獲得真正的《治療和減少肥胖法案》費用，我們堅信這不是是否的問題，而是何時的問題。我們認為它不太可能在 2024 年通過，但發生的可能性仍然很小。

The next question is coming from Seamus Fernandez from Guggenheim.

下一個問題來自古根漢的謝默斯·費爾南德斯。

Great. So really just wanted to ask, Dan, as you have assessed the Phase II SURMOUNT data in NASH, just interested to know how you are thinking about those data and the opportunity for tirzepatide in that setting or perhaps if retatrutide remains the right target molecule to move forward there? We've had a lot of speculation around some of the comments from the last quarter and just trying to firm that up and also when we're likely to see those data, I believe, they're expected at EASL, but if that is possible to confirm.

偉大的。所以真的只是想問，Dan，當您評估了NASH 中的II 期SURMOUNT 數據時，只是想知道您如何看待這些數據以及替西帕肽在這種情況下的機會，或者瑞他魯肽是否仍然是正確的目標分子往那裡走？我們對上個季度的一些評論進行了很多猜測，只是試圖證實這一點，而且當我們可能看到這些數據時，我相信，它們預計會在 EASL 上出現，但如果是這樣的話可以確認。

Dan?

擔？

Thanks, Seamus. So I'll start with the last part there. Yes, the abstract was accepted and will be presented at EASL early June. So that will be the opportunity to see the full NASH package from that Phase II trial.

謝謝，西莫。我將從最後一部分開始。是的，摘要已被接受並將於 6 月初在 EASL 上提交。因此，這將是看到第二階段試驗的完整 NASH 套件的機會。

Like we said in the last call, really exciting data. We shared some of the top line. I think tirzepatide can have a profound effect on this disease. It's a Phase II trial. Next steps here are to discuss with the FDA what the best path forward could be for tirzepatide.

就像我們在上次電話會議中所說的那樣，數據非常令人興奮。我們分享了一些最重要的內容。我認為替西帕肽可以對這種疾病產生深遠的影響。這是第二階段試驗。下一步是與 FDA 討論替西帕肽的最佳前進道路是什麼。

You're pointing out, though, that we have another choice in retatrutide which, based on biomarker data from earlier studies, could also have a profound effect of this disease. That molecule has the addition of glucagon, which is likely to have additional benefits in the liver. So important opportunities ahead and good-to-have options as we go into these discussions with regulators.

不過，您指出，我們還有瑞他魯肽的另一種選擇，根據早期研究的生物標記數據，它也可能對這種疾病產生深遠的影響。該分子添加了升糖素，這可能對肝臟有額外的好處。當我們與監管機構進行討論時，我們面臨著如此重要的機會和可有可無的選擇。

I think for MASH, like other obesity-related or metabolic related diseases, Lilly has a pretty broad portfolio, and we'll just continue to push the science to make the best possible medicines for patients.

我認為，對於 MASH，就像其他與肥胖相關或代謝相關的疾病一樣，禮來公司擁有相當廣泛的產品組合，我們將繼續推動科學發展，為患者提供最好的藥物。

The next question will be from Tim Anderson from Wolfe Research.

下一個問題將由沃爾夫研究中心的蒂姆·安德森提出。

You showed a slide, Zepbound has NBRx share market of 57% end of Q1. That makes it pretty clear that the strongest drug wins. So on that topic, just your latest thinking on upcoming competitor readouts and how they'll stack up to Zepbound on metrics of weight loss and blood sugar. So specifically, CagriSema from Novo and Amgen's 133. I know it's just the best guess, but it's what we get asked to do.

你展示了一張幻燈片，Zepbound 在第一季末擁有 57% 的 NBRx 市場份額。這很清楚地表明最強的藥物獲勝。那麼關於這個主題，請談談您對即將推出的競爭對手讀數的最新想法，以及它們如何在減肥和血糖指標上與 Zepbound 相媲美。具體來說，是 Novo 的 CagriSema 和 Amgen 的 133。

Thanks, Tim. Okay. I'll maybe hand to Dan for some comments.

謝謝，蒂姆。好的。我可能會請丹徵求一些意見。

Yes, sure, Tim. It's probably more of your job than ours to speculate on competitor readouts but I'll take a stab at it since you asked. I think on AMG 133, we've just seen really a small amount of data. So probably anything is possible and like you will be interested to see their results. Of course, there's arguments that can be heard about GIP agonism versus antagonism. We've placed our bets, and we like the data we got with GIP agonism.

是的，當然，提姆。推測競爭對手的讀數可能是你的工作，而不是我們的工作，但既然你問了，我會試試看。我認為在 AMG 133 上，我們只看到了非常少量的數據。所以也許一切皆有可能，就像您有興趣看到他們的結果一樣。當然，關於 GIP 激動與拮抗的爭論也時有發生。我們已經下了賭注，我們喜歡透過 GIP 激動劑獲得的數據。

On CagriSema, of course, adding more agonism on different pathways on top of GLP-1 is a good idea. That's what we have with tirzepatide, is a dual agonist. So CagriSema makes sense. And you'll note that we've advanced our amylin agonist to Phase II.

當然，在 CagriSema 上，在 GLP-1 的基礎上添加更多不同途徑的激動劑是一個好主意。這就是我們的替西帕肽，它是一種雙重激動劑。所以 CagriSema 是有道理的。您會注意到，我們已經將胰淀素激動劑推進到了第二階段。

Tirzepatide already is a dual agonist. Retatrutide is already a triple agonist. There's probably more we could do here at Lilly. I think across our portfolio, in Phase I and Phase II, we have nine assets that are marked for diabetes or obesity. Many of them could lead to additive weight loss on top of established mechanisms plus two more in Phase III, of course. So we have a strong portfolio here. I think tirzepatide still has unsurpassed efficacy at weight loss, but we're preparing for our next generation assets as well.

替澤帕肽已經是一種雙重激動劑。瑞他魯肽已經是一種三重激動劑。在禮來公司，我們可能還可以做更多的事情。我認為在我們的投資組合中，在第一階段和第二階段，我們有九項資產被標記為糖尿病或肥胖症。當然，其中許多可能會在既定機制的基礎上帶來額外的減重效果，再加上第三階段的另外兩個機制。所以我們在這裡擁有強大的產品組合。我認為替西帕肽在減肥方面仍然具有無與倫比的功效，但我們也在為下一代資產做準備。

The next question will be from Terence Flynn from Morgan Stanley.

下一個問題將由摩根士丹利的特倫斯·弗林提出。

Congrats on all the progress. Just was wondering if you can tell us if the IQVIA prescription data is an accurate representation of tirzepatide volumes or if it's been underrepresented at all given LillyDirect and what you know about how much is flowing through that channel? And if it is underrepresented, can you help quantify any delta for us.

祝賀所有的進展。只是想知道您是否可以告訴我們 IQVIA 處方數據是否準確地代表了替西帕肽用量，或者在 LillyDirect 的情況下它的代表性是否完全不足，以及您對流經該渠道的流量了解多少？如果代表性不足，您能否幫助我們量化任何增量。

Thanks for the question, Terence. I'll hand to Patrik for commentary on IQVIA and LillyDirect.

謝謝你的提問，特倫斯。我將請 Patrik 對 IQVIA 和 LillyDirect 進行評論。

Thanks very much, Terence. When it comes to LillyDirect, I think we are very pleased with the start. And when we look at the utilization by consumers, it's gaining traction by weeks here.

非常感謝，特倫斯。說到 LillyDirect，我認為我們對這個開始感到非常滿意。當我們觀察消費者的使用情況時，它在幾週內就獲得了關注。

If we look at the TRx data of Q1, particularly for Zepbound, it's relatively low volume that goes through LillyDirect, slightly higher in terms of NBRx. It's our understanding that what goes through LillyDirect is not by default captured by IQVIA. But IQVIA has a methodology in place to estimate what goes through LillyDirect as well.

如果我們查看第一季的 TRx 數據，特別是 Zepbound，會發現透過 LillyDirect 的交易量相對較低，而 NBRx 的交易量略高。據我們了解，IQVIA 預設不會捕獲透過 LillyDirect 傳輸的內容。但 IQVIA 也有一套方法來估計透過 LillyDirect 處理的內容。

The next question will be from Akash Tewari from Jefferies.

下一個問題將由 Jefferies 的 Akash Tewari 提出。

So your team presented data on a monotherapy GIP agonist at ADA last year, but it looks like you are moving the amylin into Phase II. Can you talk about why amylin might be preferred versus GIP as a maintenance regimen for obesity? And how your product could defer versus others when it comes to half-life and preferential agonism versus calcitonin and amylin?

因此，您的團隊去年在 ADA 上展示了單一療法 GIP 激動劑的數據，但看起來您正在將胰淀素轉移到 II 期。您能談談為什麼胰淀素可能比 GIP 更適合作為肥胖的維持方案嗎？當涉及到與降鈣素和胰淀素相比的半衰期和優先激動作用時，您的產品如何與其他產品相比？

Thank you, Akash. I'll hand to Dan for a commentary on our amylin.

謝謝你，阿卡什。我將請丹對我們的胰淀素進行評論。

Yes, there are a lot of good questions in there. Thanks for following so closely. So on the GIP, the long-acting molecule, I think primarily in that experiment, we were excited to show the benefits of isolated GIP agonism, just to answer some mechanism of action questions around tirzepatide. But as you point out, there's potential for that molecule for other indications or as a monotherapy or combination with other mechanisms.

是的，裡面有很多好問題。感謝您如此密切的關注。因此，對於 GIP 這種長效分子，我認為主要是在那個實驗中，我們很高興地展示了分離的 GIP 激動劑的好處，只是為了回答有關替澤帕肽的一些作用機制問題。但正如您所指出的，該分子有可能用於其他適應症或作為單一療法或與其他機制組合。

But of course, since tirzepatide already includes GIP agonism, we're also excited to explore other mechanisms. So that's where [elora], which is 1 of 9 different mechanisms, as I said a moment ago that we're exploring the long-acting amylin moved forward to Phase II. That has potential perhaps as a combination therapy, perhaps as a maintenance therapy, perhaps as a monotherapy, there's a lot to explore. It's still very early as it is for all of our mechanisms. So we'll keep investing and as we have data to share, we'll do that.

當然，由於替澤帕肽已經包含 GIP 激動作用，我們也很高興能探索其他機制。這就是[elora]，它是九種不同機制中的一種，正如我剛才所說，我們正在探索長效胰島澱粉樣蛋白，已進入第二階段。這也許有潛力作為一種聯合療法，也許作為一種維持療法，也許作為單一療法，還有很多值得探索的地方。對於我們所有的機制來說，現在還為時過早。因此，我們將繼續投資，當我們有數據可以分享時，我們就會這樣做。

The next question will be from Trung Huynh from UBS.

下一個問題將由瑞銀集團的 Trung Huynh 提出。

Just back on CMS recently broadening its coverage for Wegovy for certain heart conditions. I appreciate you mentioned that TROA is the main goal. But do you expect Zepbound to get added to CMS in a similar way as Wegovy? And when could this happen? Could this be after the heart failure data in 3Q? Or do we have to wait for the CVOT data?

剛回到 CMS，最近擴大了 Wegovy 對某些心臟病的覆蓋範圍。我感謝您提到 TROA 是主要目標。但您是否期望 Zepbound 以與 Wegovy 類似的方式添加到 CMS 中？什麼時候會發生這種情況？這可能是在第三季心臟衰竭數據之後嗎？還是必須等待CVOT資料？

Thanks, Trung. I'll let Patrik respond.

謝謝，特朗。我會讓派崔克回應。

Thanks, Trung. Now based upon what CMS stated early April, we actually expect to get obstructive sleep apnea for Zepbound covered by CMS and Medicare at the time of launch. And the next one then would be HFpEF assuming a positive readout and approval. And the third one would be the MMO indication. That's the sequence of our plans, assuming everything goes according to plan and we get the approval for both.

謝謝，特朗。現在，根據 CMS 4 月初的聲明，我們實際上預計 Zepbound 在推出時將由 CMS 和 Medicare 承保阻塞性睡眠呼吸中止症。假設獲得積極的讀數和批准，下一個將是 HFpEF。第三個是MMO指示。這就是我們計劃的順序，假設一切都按計劃進行，並且我們都獲得了批准。

The next question will be from Geoff Meacham from Bank of America.

下一個問題將由美國銀行的 Geoff Meacham 提出。

You guys have been asked on this before, I'm sure, but can you just review the rationale in utilizing the KwikPen just for outside the U.S. markets like Europe. I wasn't sure why this couldn't apply to the U.S. market and if this also could be a means to relieve capacity looking forward?

我敢肯定，你們以前曾被問過這個問題，但是你們能回顧一下僅在歐洲等美國市場以外使用 KwikPen 的理由嗎？我不確定為什麼這不適用於美國市場，以及這是否也可以成為緩解未來產能的一種手段？

Thanks, Geoff, for the question. Paul -- Dave, you want to weigh in? .

謝謝傑夫提出的問題。保羅 - 戴夫，你想加入嗎？ 。

Yes. Sure. And Ilya can add to this. As we think we've said on several calls now, our goal is to pursue all of the above, basically as it relates to supply options, recognizing the tremendous demand and unmet need and the constraints that exist in scaling the supply chain. So KwikPen uses existing assets, so there was less time lag. We see this first in the U.K. and now in Europe as a way to meet the needs of those patients. But we haven't ruled it out in other jurisdictions. And so we'll continue to look at every option we can to meet the needs of patients with obesity and overweight as well as with diabetes.

是的。當然。伊利亞可以補充這一點。正如我們現在在幾次電話會議上所說的那樣，我們的目標是實現上述所有目標，基本上與供應選擇相關，並認識到巨大的需求和未滿足的需求以及擴展供應鏈中存在的限制。因此 KwikPen 使用現有資產，因此時間延遲較小。我們首先在英國，現在在歐洲，將其視為滿足這些患者需求的一種方式。但我們並沒有排除在其他司法管轄區出現這種情況的可能性。因此，我們將繼續尋找各種可能的選擇，以滿足肥胖、超重以及糖尿病患者的需求。

The next question is from Kerry Holford from Berenberg.

下一個問題來自 Berenberg 的 Kerry Holford。

I'm going to take a different topic here. Looking LP(a), your new product you've now said that you're taking into Phase III. Can you confirm whether you've published new Phase II data, haven't found any. So if I'm correct, when might we see that published? And can you confirm what dose and frequency of administration you're looking at from that Phase III study? And I guess that you appear to be positioned third in that race, would be interested to hear how you expect your drug to be differentiated versus the competitor as that's already in Phase III.

我將在這裡討論一個不同的主題。看看 LP(a)，您現在表示正在進入第三階段的新產品。您能否確認是否發布了新的二期數據，目前還沒有發現。如果我是對的，我們什麼時候可以看到它發布？您能否確認您從 III 期研究中觀察到的給藥劑量和頻率？我猜您似乎在那場比賽中排名第三，有興趣了解您期望您的藥物與競爭對手相比有何差異，因為該藥物已經處於第三階段。

Thanks, Kerry. So a good multipart question, but on Lp(a), happy to talk about lepodisiran. So Dan, do you want to comment on this?

謝謝，凱瑞。這是一個很好的多部分問題，但在 Lp(a) 上，很高興談論 lepodisiran。那麼丹，你想對此發表評論嗎？

Yes. Thanks, Kerry, for the good questions here. You're right, we haven't yet published a Phase II data. But I think we just recently were able to publish the Phase I data. That was really exciting and well received. I think one of the things that people noted in our Phase I data was a very long durability of action and a very deep reduction in Lp(a) levels following a single dose of lepodisiran. We now have, of course, a Phase II data in hand and use that to design and begin the Phase III trial.

是的。謝謝克里提出的好問題。你是對的，我們還沒有發布第二階段的數據。但我認為我們最近才能夠發布第一階段的數據。這真的很令人興奮並且很受歡迎。我認為人們在我們的第一階段數據中註意到的一件事是，單劑量的 lepodisiran 具有非常長的作用持久性和 Lp(a) 水平的大幅降低。當然，我們現在手邊有第二階段的數據，並使用它來設計和開始第三階段的試驗。

I think we haven't quite disclosed dose or frequency yet, but I'm sure that will happen in time. You asked about differentiation. I think there's probably a couple of different potentials for differentiation here versus a shorter-acting ASO and a siRNA that are both in Phase III studies. Maybe first is the depth of clearance of Lp(a), we don't know how much you have to reduce Lp(a) to lead to benefits in cardiovascular outcomes and whether there's a threshold effect or a floor to this. So the depth of clearance is one.

我認為我們還沒有完全披露劑量或頻率，但我相信這會及時發生。你問的是差異化。我認為與均處於 III 期研究的短效 ASO 和 siRNA 相比，這裡可能存在幾種不同的分化潛力。也許首先是 Lp(a) 的清除深度，我們不知道需要將 Lp(a) 降低多少才能對心血管結果產生益處，也不知道是否存在閾值效應或下限。所以間隙深度是一。

The second, as you asked about, could be frequency of administration or durability of action, those two being closely linked. And the third, of course, is the population that's being studied into -- I noted we're studying secondary as well as primary prevention here. So I think we have a good package with multiple opportunities for differentiation and eager to test the Lp(a) hypothesis here this Phase III study.

正如您所問的，第二個可能是給藥頻率或行動的持久性，這兩者密切相關。當然，第三個是正在研究的人群——我注意到我們正在研究二級和一級預防。所以我認為我們有一個很好的方案，有多種分化機會，並且渴望在這個 III 期研究中測試 Lp(a) 假設。

The next question will be from Steve Scala from TD Cowen.

下一個問題將由 TD Cowen 的 Steve Scala 提出。

Given that based on all available metrics, the SURPASS-CVOT interim likely already has passed, can you confirm that the only way the trial would have stopped is if there were either a survival benefit or futility and not simply non-inferiority? And anything you can say regarding your confidence in eventually hitting superiority based on what you know so far?

鑑於基於所有可用指標，SURPASS-CVOT 中期可能已經過去，您能否確認停止試驗的唯一方法是存在生存獲益或無效，而不僅僅是非劣效性？根據您目前所了解的情況，您對最終取得優勢的信心有什麼想說的嗎？

Thanks, Steve. Dan, do you want to take the question on SURPASS-CVOT?

謝謝，史蒂夫。 Dan，您想回答有關 SURPASS-CVOT 的問題嗎？

Sure. Thanks, Steve. As you know, we do our best not to comment on interim analyses, although many of our different trials can incorporate interim analyses. But when we do talk about the risks, unintentional unblinding of results, for that reason, we prefer not to do that.

當然。謝謝，史蒂夫。如您所知，我們盡力不對中期分析發表評論，儘管我們的許多不同試驗可以納入中期分析。但當我們確實談論風險、無意識揭盲結果時，出於這個原因，我們寧願不這麼做。

You're right that the primary analysis of the study and the design is around noninferiority versus what we are ready to know to be a very good drug that reduces cardiovascular risk, and that's Trulicity. So it's designed as a noninferiority trial. Of course, when the final data come, we would be delighted to see even superiority.

你是對的，這項研究和設計的主要分析是圍繞非劣效性與我們準備知道的一種非常好的降低心血管風險的藥物（即 Trulicity）進行比較。因此它被設計為非劣效性試驗。當然，當最終數據出來時，我們會很高興看到甚至更優越。

You asked about our confidence. Confidence continues to increase for this readout. In fact, as disclosed in the prepared remarks today, we got additional data here even from the OSA study that should make us feel more confident, not just the benefit in sleep apnea, which itself could lead to cardiovascular benefits, but actually the weight loss. And I think there are some concerns about weight loss of different populations and different trials and males, females, et cetera. So some of that was discharged here. So we remain excited and look forward to getting that data when the study's complete.

你問我們的信心。人們對此讀數的信心持續增加。事實上，正如今天準備好的演講中所披露的，我們甚至從OSA 研究中獲得了更多數據，這些數據應該讓我們感到更加自信，不僅是對睡眠呼吸中止症的益處（睡眠呼吸中止症本身可能會帶來心血管益處），而且實際上是體重減輕。我認為對於不同人群和不同試驗以及男性、女性等的體重減輕存在一些擔憂。所以其中一些是在這裡排出的。因此，我們仍然感到興奮，並期待在研究完成後獲得這些數據。

The next question will be from Evan Seigerman from BMO Capital Markets.

下一個問題將由 BMO 資本市場的 Evan Seigerman 提出。

I wanted to touch on donanemab with the AdCom approaching. Can you discuss how your -- if your confidence has changed in the asset? And maybe any specific points that you hope will be addressed during this discussion with these outside experts.

隨著 AdCom 會議的臨近，我想談談多納奈瑪 (donanemab)。如果您對資產的信心發生了變化，您能談談您的看法如何變化嗎？也許您希望在與這些外部專家的討論中能夠解決任何具體問題。

Thanks, Evan. Anne, you want to discuss [donanemab] and AdCom?

謝謝，埃文。 Anne，您想討論 [donanemab] 和 AdCom 嗎？

Yes. Thanks so much for the question. And we are incredibly confident in donanemab's potential and the fact that it offers very meaningful benefits to people with early symptomatic Alzheimer's disease and just the overall approvability of the package. We do look forward to seeing there's questions. We haven't received those yet. I think that what we'll anticipate really is discussions around the safety and efficacy of donanemab. And those -- the safety and efficacy profile remain very consistent with what we published and presented. So nothing new there.

是的。非常感謝您的提問。我們對 donanemab 的潛力充滿信心，事實上它為早期症狀性阿茲海默症患者提供了非常有意義的益處，並且該方案的整體認可度也很高。我們確實期待看到有人提出問題。我們還沒有收到那些。我認為我們真正期待的是圍繞多南單抗的安全性和有效性進行討論。這些－安全性和有效性概況與我們發布和介紹的內容仍然非常一致。所以沒有什麼新東西。

We do expect there's a couple of unique aspects to our trial that we anticipate they'll want to discuss. One is around limited duration dosing. We think this is an incredibly important feature of donanemab, the chance to stop dosing when you've cleared the plaques. And donanemab clears them robustly and rapidly so we think that allows for this limited duration dosing approach. So we really do look forward to getting into that data and having the advisers see that and respond to it.

我們確實希望我們的試驗有一些獨特的方面，我們預計他們會想要討論這些方面。一是限時給藥。我們認為這是多南單抗的一個極其重要的特徵，即清除斑塊後有機會停止給藥。多納奈馬布可以快速有效地清除它們，因此我們認為這可以實現這種有限持續時間的給藥方法。因此，我們確實期待了解這些數據，並讓顧問看到這些數據並做出回應。

Another unique aspect is assessing tau at baseline. This is important for the field that we understand the prognostic factor of tau, and that was able to be earned. But what we saw in the trial was all patients benefited regardless of tau level with those early in the disease doing even better. It's one of the reasons that we remain so enthusiastic about TRAILBLAZER-3. And while Dan didn't mention that in his remarks, I think we remain even more enthusiastic about the opportunity to intervene earlier based on what we saw in that early population, the people with low tau and those that had no tau with such strong biomarker results. I think you probably remember the data that patients in the earliest part of our study had a 60% slowing. And we believe that could be even stronger as you get into the earlier patients that are preclinical.

另一個獨特的方面是評估基線 tau 蛋白。這對於我們了解 tau 的預後因素這一領域非常重要，而且這是可以實現的。但我們在試驗中看到的是，無論 tau 蛋白水平如何，所有患者都受益，而疾病早期患者的情況甚至更好。這就是我們對 TRAILBLAZER-3 保持如此熱情的原因之一。雖然Dan 在他的演講中沒有提到這一點，但我認為，根據我們在早期人群、低tau 蛋白含量的人和沒有tau 蛋白含量且具有如此強生物標誌物的人群中所看到的情況，我們仍然對早期介入的機會更加熱衷。我想您可能還記得我們研究早期階段患者的速度減慢了 60% 的數據。我們相信，當您進入臨床前的早期患者時，這種情況可能會更加強烈。

But maybe just one remark. In the meantime, though, this is not time loss. We'll continue to make sure the health care system is ready. We're going to make sure that we launch into an even stronger market with potential approval. So we're making the most of this time and look forward to the outcomes, as Dan said, in mid-'24 and answering any questions that they have.

但也許只是一句話。但同時，這並不是時間損失。我們將繼續確保醫療保健系統做好準備。我們將確保我們進入一個更強大的市場並獲得潛在的批准。因此，我們正在充分利用這段時間，並期待丹所說的 24 年中期的結果，並回答他們提出的任何問題。

Next question will be from David Risinger from Leerink Partners.

下一個問題將由 Leerink Partners 的 David Risinger 提出。

And let me add my congrats on the progress and the guidance raise. So my question is on orforglipron. Novo Nordisk has raised some concerns about the scalability of orforglipron manufacturing given its complexity. I haven't spoken to Novo directly, but someone told me that they mentioned there are 35 steps in the process. I don't know if that's true. But could you please discuss how Lilly is building out its manufacturing capacity and whether the company expects to be able to meet global demand in the Western world after launch in 2026? Or whether we, the investment community, should expect supply constraints and should be guarded about how we try to model orforglipron's ramp after launch?

讓我對進展和指導意見的提高表示祝賀。所以我的問題是關於orforglipron。鑑於 orforglipron 製造的複雜性，諾和諾德對它的可擴展性提出了一些擔憂。我沒有直接與 Novo 交談過，但有人告訴我，他們提到這個過程有 35 個步驟。我不知道這是不是真的。但您能否討論一下禮來公司如何建立其製造能力以及該公司是否預計能夠在 2026 年推出後滿足西方世界的全球需求？或者，我們投資界是否應該預期供應會受到限制，並且應該對我們如何嘗試建模或forglipron在推出後的成長保持警惕？

Thanks, Dave. I'll hand over to our Dave Ricks here.

謝謝，戴夫。我將把工作交給我們的戴夫·里克斯 (Dave Ricks)。

Okay. Great. Dave, great to hear from you. I mean, first of all, it is true that orforglipron is a complicated large small molecule, a large small molecule, if you were, and there are many steps in the process. You can read about them in our patent filings, I think.

好的。偉大的。戴夫，很高興收到你的來信。我的意思是，首先，orforglipron 確實是一個複雜的大的小分子，一個大的小分子，如果你是的話，並且這個過程中有很多步驟。我想你可以在我們的專利申請中讀到它們。

But Lilly, maybe unlike other companies, we've made small molecules for a long time. We're capable of doing it. We understand how to put them together, and we've got a defined process to do it for orforglipron.

但禮來公司，也許與其他公司不同，我們長期以來一直在生產小分子。我們有能力做到這一點。我們了解如何將它們組合在一起，並且我們有一個明確的流程來為 orforglipron 做到這一點。

So the API production, while a long process and maybe complicated relative to other small molecules, is something we're super confident in and have our arms around. The finish process is really the big advance over using injectables because here, we're just tablet stamping or tablet -- capsule making, which are dry processes we understand extremely well.

因此，API 的生產雖然是一個漫長的過程，而且相對於其他小分子來說可能很複雜，但我們對此非常有信心並全力支持。與使用注射劑相比，最終製程確實是一個巨大的進步，因為在這裡，我們只是片劑沖壓或片劑膠囊製造，這是我們非常了解的乾式工藝。

I think the big gain here will be the fact that both for synthetic chemistry and capsule making and tablet making, there is already capacity on planet Earth that is significant. And so unlike the parenteral side where we've been talking about injectables, a new capacity needs to be built in which we're doing aggressively, as Anat commented on earlier. Here, there's a lot of partners we can access as well as our own substantial network for dry product finish and API production. So pretty confident here.

我認為這裡的最大收穫將是這樣一個事實：無論是合成化學、膠囊製造還是片劑製造，地球上已經擁有巨大的產能。因此，與我們一直在談論注射劑的注射劑方面不同，我們需要建立一種新的能力，我們正在積極開展這項工作，正如阿納特之前評論的那樣。在這裡，我們可以接觸到許多合作夥伴，以及我們自己用於乾產品精加工和 API 生產的龐大網路。在這裡非常有信心。

Now will we stick the landing on exact doses and quantities in every instance? We're not guaranteeing that, but I think the picture will be quite a bit different should orforglipron prove to be safe and effective in the Phase III studies. Again, that's in '25, so we can expect launch maybe a year after that, and that's an important event in the time course of the incretin class.

現在我們是否會在每種情況下都堅持精確的劑量和數量？我們不能保證這一點，但我認為，如果 orforglipron 在 III 期研究中被證明是安全有效的，情況將會有很大不同。再說一次，那是在 25 年，所以我們預計可能會在一年後推出，這是腸促胰素類時間進程中的一個重要事件。

Next question is coming from Louise Chen from Cantor.

下一個問題來自 Cantor 的 Louise Chen。

I just wanted to ask you about your next wave of obesity drug. It looks like you've got half a dozen of these in development. And where do you think you can most differentiate yourself?

我只是想問你關於下一波肥胖藥物的情況。看起來您已經開發了六種這樣的產品。您認為自己最能在哪些方面脫穎而出？

Dan, do you want to comment on earlier phase obesity?

丹，你想對早期肥胖發表評論嗎？

Yes. Thanks, Louise. We're excited about that portfolio of earlier-stage obesity molecules. I think there's a number of opportunities for improvement over even an excellent drug like tirzepatide. We think about the quality of weight loss as one aspect. So for example, even on tirzepatide, we see the ratio of lean to fat mass approved as patients lose weight on these drugs. Could we make it improve even faster with the muscle stimulating agents like bimagrumab? But maybe that's under investigation.

是的。謝謝，路易絲。我們對早期肥胖分子的組合感到興奮。我認為即使是像替西帕肽這樣的優秀藥物，也有很多改進的機會。我們將減肥的品質視為一方面。例如，即使在服用替西帕肽時，我們也看到隨著患者使用這些藥物減輕體重，瘦肉與脂肪的比例也得到了批准。我們能否使用 bimagrumab 等肌肉刺激劑使其改善得更快？但也許這正在調查中。

Tirzepatide is very well tolerated, but some people stop taking it because of GI side effects. Could we have drugs that have fewer side effects? Maybe that could be possible. Tirzepatide is given as a once a weekly injection. Most patients find that to be acceptable. But probably with less frequent injections, that could lower the burden on manufacturing and make it easier to use for patients. So that's another avenue of exploration.

替澤帕肽的耐受性非常好，但有些人因為胃腸道副作用而停止服用。我們能否開發出副作用較少的藥物？也許那是可能的。替澤帕肽每週注射一次。大多數患者認為這是可以接受的。但透過減少注射頻率，可能可以減輕生產負擔，並使其更容易為患者使用。這是另一個探索途徑。

There are some patients who don't achieve their desired levels of weight loss even on a powerful drug like tirzepatide. And so that's another avenue.

有些患者即使使用替澤帕肽等強效藥物也無法達到預期的減重水準。這是另一條途徑。

Finally, across different indications, and I spoke earlier of NASH, that are related to metabolic disease, there could be different activities that proved more or less beneficial for these other related diseases. So that's another avenue of differentiation.

最後，在不同的適應症中，我之前談到了與代謝疾病相關的 NASH，可能有不同的活動被證明對這些其他相關疾病或多或少有益。這是差異化的另一個途徑。

I think we're just at the beginning of probably what will be seen as a multi-decade investments in treating abnormal metabolism and all diseases that come with that. And I'm really proud and pleased that Lilly has what must be the strongest pipeline in this area in the industry.

我認為我們才剛開始，可能會被視為治療異常代謝及隨之而來的所有疾病的數十年投資。我感到非常自豪和高興的是，禮來公司擁有業內該領域最強大的產品線。

The next question is from Chris Shibutani from Goldman Sachs.

下一個問題來自高盛的 Chris Shibutani。

Thanks, Chris. Paul, next question?

謝謝，克里斯。保羅，下一個問題？

Can you hear me?

你聽得到我嗎？

Oh, yes, there you are. Go ahead, Chris.

哦，是的，你在那裡。繼續吧，克里斯。

Wanted to ask about the supply and dynamic -- and the demand and when those two might come closer together? Previously, Anat, you've been quite specific in your vocabulary and saying that, that was something that could possibly happen in 2025. Dave, you were in front of a group that we hosted and I think you gave a little bit of a broader range. What's the latest that you would like to communicate based upon all the progress that you're making, the acquisition of Wisconsin facility, et cetera, about a potential timing for that supply-demand dynamic to come closer together?

想詢問供應和動態以及需求以及這兩者何時可能更接近？此前，Anat，您的詞彙非常具體，並說這可能在 2025 年發生。根據您正在取得的所有進展、威斯康辛州工廠的收購等，您想就供需動態更加接近的潛在時機進行交流嗎？

Thanks, Chris. Anat?

謝謝，克里斯。阿納特？

Yes. Let me start on this. So I would say that, as I said in my prepared remarks, we expect that the supply and demand situation will remain quite tight in the near term as well as the midterm. And just to clarify, it's not that we have a production issue. Our manufacturing facilities are progressing incredibly well, and I'm incredibly proud of the work done by our M&Q colleagues around the world. Clearly, we have sites working 24/7. We're doing construction overnight. We're making the right investments and so we're progressing rapidly as you've seen evidenced by the results as well as the raise we did for the year.

是的。讓我從這個開始。所以我想說，正如我在準備好的演講中所說，我們預計近期和中期供需情況仍將相當緊張。需要澄清的是，這並不是我們遇到了生產問題。我們的生產設施進展得非常順利，我對世界各地 M&Q 同事所做的工作感到非常自豪。顯然，我們的站點 24/7 都在運行。我們正在連夜進行施工。我們正在做出正確的投資，因此我們正在迅速取得進展，正如您所看到的結果以及我們今年所做的加薪所證明的那樣。

But the demand is strong, which shouldn't be a surprise given the health benefits that these products provide to patients, highly efficacious and safe medicines. And I expect that this will continue through the year, even with the significant ramp that we have, and we'll add more supply across different presentations, both with the auto-injector as well as the KwikPen. But even with that, I expect that the demand will be -- will outpace supply through this year. Potentially next year, obviously, we'll see. We'll continue to invest and ramp as we go into next year, but it could be quite some time.

但需求強勁，考慮到這些產品為患者提供的健康益處、高效且安全的藥物，這並不奇怪。我預計這種情況將持續到今年，即使我們有顯著的成長，我們將在不同的演示中增加更多的供應，包括自動注射器和 KwikPen。但即便如此，我預計今年的需求將超過供應。顯然，明年可能會發生，我們拭目以待。進入明年，我們將繼續投資和擴大規模，但這可能需要相當長的時間。

We talked earlier about orforglipron, should we have positive Phase III readout that provides another relief valve in terms of just offering a different presentation, as Dave mentioned, which utilizes a different set of infrastructure within our manufacturing organization available capacity globally. So it will be in a stepwise fashion. We'll continue to update investors as we progress through the year and coming years.

我們之前討論過orforglipron，我們是否應該有積極的第三階段讀數，提供另一個安全閥，就像戴夫提到的那樣，僅提供不同的演示，它利用我們製造組織在全球可用能力內的一組不同的基礎設施。因此，這將是逐步進行的。隨著今年和未來幾年的進展，我們將繼續向投資者通報最新情況。

Next question will be from Carter Gould from Barclays.

下一個問題將由巴克萊銀行的卡特·古爾德提出。

I wanted to dive into bimagrumab ahead of the Phase IIb data forthcoming. Can you talk for a bit around the importance of showing stat sig or clear dose response across the composition of the weight loss drivers and maybe as well as the importance of not blunting the overall weight loss as you contemplate a move to Phase III potentially?

我想在 IIb 期數據即將發布之前深入研究 bimagrumab。您能否談談在減重驅動因素的組成中顯示統計數據或明確劑量反應的重要性，以及在您考慮可能進入第三階段時不削弱整體減肥的重要性？

Thanks, Carter, for the question. Dan, you want to comment on bimagrumab?

謝謝卡特提出的問題。 Dan，您想對 bimagrumab 發表評論嗎？

Yes. Thanks, Carter. It's a good question. Bimagrumab is a very different mechanism of weight loss versus incretins but one that we think could be important in combination with incretins. So bimagrumab, we think will likely have important effects on adipose tissue as well as muscle mass. And so our hope is to see increased muscle mass and increased ratio, I should say, of lean to fat mass by combining bimagrumab with incretins.

是的。謝謝，卡特。這是一個好問題。 Bimagrumab 是一種與腸促胰島素截然不同的減重機制，但我們認為與腸促胰島素合併使用可能很重要。因此，我們認為 bimagrumab 可能會對脂肪組織和肌肉質量產生重要影響。因此，我們的希望是透過將 bimagrumab 與腸降血糖素結合來增加肌肉質量和增加瘦肉與脂肪的比例。

In this present study, it's being evaluated both as monotherapy and in combination with semaglutide at different doses. So we'll see if weight loss effects on fat tissue stack and we'll see if effects on lean body mass that we're seeing in previous bimagrumab monotherapy studies work in combination with incretin. Looking forward to seeing that data.

在本研究中，它作為單一療法以及與不同劑量的索馬魯肽聯合療法進行了評估。因此，我們將看看減重是否對脂肪組織疊加有影響，我們將看看我們在先前的 bimagrumab 單一療法研究中看到的對去脂體重的影響是否與腸促胰島素聯合使用。期待看到該數據。

The next question is coming from Kripa Devarakonda from Truist Securities.

下一個問題來自 Truist Securities 的 Kripa Devarakonda。

Congrats on all the progress. I have a question about your radiopharma pipeline. You mentioned PNT2002 in your oncology pipeline. Can you talk about how you see that advancing? And given what you've seen so far, where you see this being placed in the landscape in terms of market share?

祝賀所有的進展。我對你們的放射性藥物管道有疑問。您在腫瘤學研發管線中提到了 PNT2002。您能談談您如何看待這項進展嗎？考慮到您到目前為止所看到的情況，您認為它在市場份額方面處於什麼位置？

Thanks, Kripa, for the question. Jake, calling you to maybe opine a little bit on our radioligand efforts, PNT2001 in particular?

謝謝克里帕提出的問題。 Jake，請您對我們的放射性配體工作（特別是 PNT2001）發表一點意見？

Yes, happy to. Thanks for the question. We're really excited about bringing radiopharmaceuticals into the portfolio by way of the acquisition of POINT Biopharma, and we are supplementing that acquisition with additional work through our discovery labs and the ability to make these medicines ourselves. So I expect we'll have more to talk about in terms of additional medicines over the course of the next couple of years in addition to PNT2001.

是的，很高興。謝謝你的提問。我們非常高興透過收購 POINT Biopharma 將放射性藥物納入產品組合，並且我們正在透過我們的發現實驗室和自己製造這些藥物的能力進行額外的工作來補充這項收購。因此，我預計在接下來的幾年中，除了 PNT2001 之外，我們還會有更多關於其他藥物的討論。

But specific to that question, 2001 is a PSMA-directed therapy for prostate cancer conjugated to actinium, the alpha emitter. And I think while actinium holds a lot of promise over lutetium, particularly in the context of creating double-stranded DNA breaks versus single stranded and the ability to perhaps drive more efficacy for patients of prostate cancer. I think one of the limitations of the existing agents is that they probably cause too much salivary gland toxicity to be real durable products.

但針對這個問題，2001 是一種針對前列腺癌的 PSMA 標靶療法，與錒（α 發射體）結合。我認為錒比镥更有希望，特別是在相對於單股產生雙股 DNA 斷裂的背景下，以及可能為攝護腺癌患者帶來更高療效的能力。我認為現有藥劑的限制之一是它們可能會導致過多的唾液腺毒性，無法成為真正的耐用產品。

And so the POINT team designed a novel PSMA-directed ligand with increased tumor uptake relative to the salivary gland in order to drive more therapeutic index using actinium as the payload. So we're just getting started with the Phase I experience right now. So I don't have a lot to say about what we're seeing just yet. But the preclinical package looked really interesting and differentiated from the other PSMA ligands that exist out there. So we're looking forward to putting it through its Phase I paces, and we'll see what we have.

因此，POINT 團隊設計了一種新型 PSMA 導向配體，相對於唾液腺，該配體具有增加的腫瘤攝取，以便使用錒作為有效負載來驅動更高的治療指數。所以我們現在才剛開始第一階段的體驗。因此，對於我們目前所看到的情況，我還沒有太多要說的。但臨床前包裝看起來非常有趣，並且與現有的其他 PSMA 配體不同。因此，我們期待著它通過第一階段的步伐，我們將看看我們擁有什麼。

Depending on the clinical profile, I think there's the potential to improve outcomes in patients that have already seen a lutetium-based agent maybe go ahead of that and compete with the lutetium-based agents or perhaps even go even earlier in therapy as PSMA expression really exists in the continuum of prostate cancer care. So more to come on that as we define the clinical profile in the Phase I.

根據臨床情況，我認為已經使用基於镥的藥物的患者有可能改善結果，可能會提前並與基於镥的藥物競爭，甚至可能更早進行治療，因為 PSMA 表達確實如此存在於前列腺癌護理的連續過程中。當我們定義第一階段的臨床概況時，還會有更多內容。

Paul, I think we've got time for maybe one more question. We're right at 11. So maybe a final question in the queue.

保羅，我想我們還有時間再問一個問題。現在是 11 點。

Okay. And the final question today is coming from James Shin from Deutsche Bank.

好的。今天的最後一個問題來自德意志銀行的 James Shin。

I just wanted to try and reconcile the guidance lift with the 1.5x saleable doses being maintained.

我只是想嘗試協調指導提升與維持的 1.5 倍可銷售劑量。

Okay. James, maybe I'll give to Anat to talk about the guidance and how the guidance raise relates to the 1.5x dose comments.

好的。 James，也許我會向 Anat 談談指導意見以及指導意見的提高與 1.5 倍劑量評論之間的關係。

So let's start with the 1.5 dose -- sellable dose comment that I made on the guidance call in February. So that reference is not a number of devices, but number of sellable doses. And as we ramp up capacity for KwikPen, recall that unlike the single-use vial or the auto-injector, that KwikPen is a multidose device that has multiple doses available for patients.

因此，讓我們從我在 2 月的指導電話會議上發表的 1.5 劑量——可銷售劑量評論開始。因此，該參考不是設備的數量，而是可銷售劑量的數量。當我們提高 KwikPen 的容量時，請記住，與一次性小瓶或自動注射器不同，KwikPen 是一種多劑量設備，可為患者提供多種劑量。

That comment referred to the second half of this year versus the second half of last year. So we're expecting that total saleable doses this year in the second half will be at least 1.5x where we were second half of last year. That remains unchanged. But the level of confidence we have in our ability to progress on each node of our capacity that's coming online or will get approved, et cetera, has just increased. There are multiple of these throughout the year. Multiple of these have occurred. Some will occur as -- I gave the KwikPen as one example.

該評論指的是今年下半年與去年下半年的情況。因此，我們預計今年下半年的總可銷售劑量將至少是去年下半年的 1.5 倍。這仍然沒有改變。但是，我們對即將上線或將獲得批准等能力的每個節點的進展能力的信心程度剛剛增加。全年都有多個這樣的情況。此類情況已發生多次。有些情況會發生——我以 KwikPen 為例。

Think about a construction of a site, for example, Concord in North Carolina, which we said will become operational by end of the year, and we'll start seeing products next year. That construction has concluded. Lines are installed, and we need to run qualifications, get approval, et cetera. There are multiple nodes of these across our own manufacturing sites as well as external and that they all need to come online to get to where we need in terms of the full year guidance. But our confidence as the year progresses -- as the year has progressed, our confidence in that has increased, but it remains the -- at least 1.5.

考慮一下建造一個站點，例如北卡羅來納州的康科德，我們說該站點將在今年年底投入運營，我們將在明年開始看到產品。該建設已經結束。線路安裝好了，還需要運作資格、審核等等。我們自己的製造工廠以及外部製造工廠都有多個節點，它們都需要連網才能達到我們全年指導所需的位置。但隨著時間的推移，我們的信心——隨著時間的推移，我們對此的信心增加，但仍然是——至少 1.5。

Thanks, Anat. Great. Well, thanks for your time today, everyone, and we appreciate you participating in today's earnings call and your interest in our company. Please follow up with the IR team if you have any additional questions that we didn't address today, and have a great day. Thanks.

謝謝，阿納特。偉大的。好的，感謝大家今天抽出寶貴的時間，我們感謝您參加今天的財報電話會議以及您對我們公司的興趣。如果您還有我們今天未解決的任何其他問題，請與 IR 團隊聯繫，祝您有美好的一天。謝謝。

Thank you. And 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 June 4 at midnight. You may access the replay system at any time by dialing (800) 332-6854 and entering the access code 317750. International dialers can call (973) 528-0005. Thank you for your participation. You may now disconnect your lines.

謝謝。女士們、先生們，我們今天的會議到此結束。本次會議將於下午 1:00 開始重播。今天一直持續到 6 月 4 日午夜。您可以隨時撥打 (800) 332-6854 並輸入存取代碼 317750 存取重播系統。感謝您的參與。現在您可以斷開線路。