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，感謝您的耐心等待，歡迎參加禮來公司2024年第一季財報電話會議。 （操作說明）

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

現在我將會議交給主持人，投資者關係高級副總裁喬·弗萊徹先生。請開始吧。

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 Michala Irons, Mike Sprengnether and Lauren Zierke of the IR team.

謝謝保羅，大家早安。感謝各位參加禮來公司2024財年第一季財報電話會議。我是投資者關係資深副總裁喬·弗萊徹。今天與我一同參加電話會議的還有：禮來董事長兼首席執行官戴夫·里克斯；首席財務官阿納特·阿什肯納齊；首席科學官兼禮來免疫學總裁丹·斯科夫龍斯基博士；禮來神經科學總裁安妮·懷特；禮來國際總裁伊利亞·尤法；禮來肥胖此外，投資者關係團隊的米卡拉·艾恩斯、邁克·斯普倫格內瑟和勞倫·齊爾克也參加了會議。

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。實際結果可能因多種因素而與預期有重大差異，包括投影片2中所列的因素。有關可能導致實際結果出現重大差異的因素的更多信息，請參閱我們最新的10-K表格以及隨後向美國證券交易委員會提交的文件。

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.

我們提供的產品和研發管線資訊旨在為投資界提供參考，並非用於推廣，也不足以作為投資決策的依據。接下來，我們將進入正式發言環節，請注意，我們的演講將重點放在非GAAP財務指標。

Now I'll turn the call over to Dave.

現在我把電話交給戴夫。

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以及業務的持續成長動能感到滿意，這為我們今年的加速成長奠定了良好的基礎。我們的目標是為有需要的人提供創新藥物。 2024年，我們將增加對員工、產品上市、拓展新藥研發管線（包括透過業務拓展）以及提升生產網路產能的投入。本季的業績延續了我們在2023年取得的強勁成長動能。

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.

在第4張投影片中，您可以查看財務績效詳情以及與我們的策略目標相關的進展。第一季營收成長26%，其中新產品銷售額較去年同期成長近18億美元。我們實現了多項關鍵的研發管線里程碑，包括：tirzepatide治療中重度阻塞性睡眠呼吸中止症的III期臨床試驗取得積極結果；Mounjaro多劑量注射筆KwikPen在歐洲獲批；mirikizumab在美國和歐盟提交用於治療中重度活動性克隆氏症的上市申請；lebrikizumab在美國重新提交用於治療中重度異位性皮膚炎的上市申請；以及啟動lepodisiran的III期臨床試驗，以評估其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雄心勃勃的生產擴張計畫順利實施。我們近期簽署協議，收購位於威斯康辛州普萊森特普雷里市的Nexus Pharmaceuticals公司的注射劑生產廠。這座先進的生產廠已獲得FDA批准，我們計劃於2025年底投產。本月初，我們已在德國破土動工興建先前宣布的注射劑生產基地。同時，我們也在現有生產設施中努力提高產量和生產效率，以滿足市場需求。

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.

我們用於治療 Mounjaro 的多劑量 KwikPen 注射筆近期獲得 EMA 批准，即將上市，這將為歐洲和其他國際市場釋放新的供應能力。同時，我們也看到禮來公司和 CDMO 在美國的現有生產線正在穩步推進。

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.

我們正按計劃穩步推進產能擴張計劃，這是公司史上規模最大的擴張計劃。此外，我們在第一季派發了超過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.

在第 5 張幻燈片中，您將看到自我們第四季度財報電話會議以來的主要事件列表，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.

現在我把電話交給Anat，讓他來回顧一下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。第一季營收成長26%，主要得益於新產品，尤其是Mounjaro和Zepbound。毛利率（佔營收的百分比）從2023年第一季的78.4%成長至2024年第一季的82.5%。本季毛利率的成長得益於更高的實際售價、更豐富的產品組合以及（在較小程度上）生產成本的降低。

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、銷售和管理費用成長了12%，主要原因是為支持當前和未來產品上市而進行的推廣活動，以及薪資和福利成本的增加。研發費用增加了27%，主要原因是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前列腺癌計畫相關的約7,500萬美元的一次性支出。

In Q1, we recognized acquired IPR&D charges 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，我們確認了1.11億美元的收購智慧財產權研發費用，導致每股盈餘減少0.10美元。第一季營業收入成長63%，主要得益於新產品收入的成長，但部分被營業費用成長所抵銷。第一季實際稅率為11.9%，低於2023年第一季的12.8%，主要原因是2024年第一季淨一次性稅收優惠高於2023年同期。第一季每股收益為2.58美元，較2023年第一季成長59%，已計入兩個時期因收購智慧財產權研發費用造成的0.10美元負面影響。

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、費率和銷售對收入成長的影響。第一季度，美國營收成長了 28%，主要得益於 Mounjaro、Zepbound 和 Verzenio 的成長。市場對我們腸促胰素類藥物的空前需求導致 Trulicity、Mounjaro 和 Zepbound 在季度末出現批發商的訂單積壓。美國實際售價上漲了 16%，這主要得益於 Mounjaro 的優惠卡和折扣卡的推廣。

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.

轉向歐洲市場。營收成長再次強勁，以固定匯率計算成長了 29%，主要得益於 Verzenio 和 Mounjaro 的銷量以及與分銷和剝離協議相關的付款。

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.

日本市場營收以固定匯率計算成長2%。銷量成長7%，主要得益於Mounjaro和Verzenio的業績成長，但部分被Trulicity銷量下降以及基期一項合作里程碑事件所抵消。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.

業務拓展至中國。第一季營收以固定匯率計算成長4%。銷售成長主要得益於Tyvyt，但部分被Olumiant和Cialis的銷售成長所抵銷。

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.

世界其他地區的營收以固定匯率計算成長了 31%，主要得益於 Mounjaro 的銷售成長，Verzenio 和 Jardiance 的銷售成長則相對較小。

Slide 8 provides additional perspective across our product categories. First, I would like to highlight Verzenio, which saw worldwide sales increase 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.

第 8 張投影片從更廣闊的視角展現了我們各個產品類別的概況。首先，我想重點介紹 Verzenio，該產品第一季全球銷售額成長了 40%，這主要得益於早期乳癌適應症的持續銷售成長。 Jaypirca 的全球收入成長至 5,000 萬美元，自 2023 年 12 月獲準用於治療慢性淋巴球白血病 (CLL) 以來，其季度環比增長速度加快。我們期待隨著未來 III 期臨床試驗結果的公佈，能夠讓更多患者受益於這種藥物。

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 Q1 2024 amid 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.

第二季度，Mounjaro全球銷售額為18億美元，美國銷售額為15億美元，高於2023年第一季的5.68億美元和5.36億美元。 Mounjaro在美國的季度環比收入受到以下因素的影響：2023年第四季回扣和折扣預估調整帶來的一次性收益，以及2024年第一季在強勁需求下通路庫存下降。商業管道和D部分（美國聯邦醫療保險）的准入水平與我們在上次財報電話會議上提到的高水平一致，並且與已上市的注射用腸促胰素藥物的准入水平接近。

The demand for tirzepatide is very strong. And each week, hundreds of thousands of people fill scripts for Mounjaro and Zepbound. Yet we understand the frustration from those facing prescription delays or uncertainties getting 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, that production of saleable doses of incretin medicines 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.

替澤帕肽的需求非常強勁。每週都有數十萬人憑處方購買蒙加羅（Mounjaro）和澤普邦德（Zepbound）。然而，我們也理解那些面臨處方延遲或無法及時獲得藥物的患者所感受到的沮喪。儘管我們正不懈努力提高供應量，並預計下半年出貨量將顯著增長，但需求仍超過增加後的供應量。我們仍有望實現今年稍早設定的目標，即2024年下半年可銷售劑量腸促胰素類藥物的產量至少是2023年下半年的1.5倍。在中短期內，我們預期銷售成長將主要取決於我們的生產和出貨能力。

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 indications 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，我們欣喜地宣布，Mounjaro公司的多劑量KwikPen胰島素注射裝置近期已獲歐盟批准，此前該產品已於今年稍早在英國獲得批准。此次核准的適應症涵蓋第2型糖尿病和慢性體重管理，因為在歐洲，這兩種適應症都歸於同一品牌。雖然各國上市時間會有所不同，但我們預計在未來幾週內在歐盟開始上市。

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26%。受銷售下滑影響，美國Trulicity營收下降30%，主因是供應受限和市場競爭加劇。此外，為盡量減少對現有患者的影響，我們採取了一系列措施，包括告知醫療專業人員暫勿為新患者啟動Trulicity治療，這些措施也對國際市場的銷售造成了一定影響。

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, patient access in this market is a two-step process typically requiring 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 through employer opt-ins and early progress is encouraging.

請看投影片9。 Zepbound在美國的上市進展非常強勁，第一季銷售額超過5億美元。我們正在迅速擴大Zepbound在美國的市場覆蓋範圍。截至4月1日，我們在商業通路的覆蓋率已達到約67%。需要提醒的是，在這個市場，患者獲得藥物通常需要兩個步驟，即在藥品福利管理機構（PBM）承保後，雇主選擇加入抗肥胖藥物附加條款。我們將繼續致力於擴大藥物覆蓋範圍，包括與PBM合作以及透過雇主選擇加入的方式，目前取得的初步進展令人鼓舞。

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

第 10 頁，我們將提供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.

第11頁投影片展示了更新後的2024年財務預期。鑑於我們業務的強勁表現以及對下半年持續加速成長的預期，我們將全年營收預期上下限均上調20億美元，達到424億美元至436億美元之間。此次上調主要得益於Mounjaro和Zepbound的出色業績，以及我們對2024年剩餘時間產能擴張的更清晰的認識和更強的信心。此次更新後，本公司全年營收年增率預計約為26%（取中間值），核心業務營收年增率預計約35%（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.

鑑於營收預期已更新，我們預計按報告準則計算的毛利率（扣除營運支出後）除以營收，將在32%至34%之間；按非GAAP準則計算，則將在33%至35%之間，這意味著毛利率將進一步提升。我們重申對其他收入、支出和稅率的預期，該預期現已納入第一季業績。

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，加上第一季每股 0.10 美元的智慧財產權研發費用，我們現在預計每股收益（按報告基準）將在 13.05 美元至 13.55 美元之間，按非公認會計準則基準則在 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.

現在我將把電話交給丹，讓他專注於研發方面的進展。

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 obesity 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，Anat。首先，我想和大家分享我們本月初發布的振奮人心的消息。那就是SURMOUNT-OSA研究的III期臨床試驗取得了正面的成果。該研究評估了替拉帕肽治療肥胖合併中重度阻塞性睡眠呼吸中止症（OSA）成年患者的療效。 OSA是一種睡眠呼吸障礙，其特徵是睡眠期間上呼吸道完全或部分塌陷。 OSA可導致嚴重的心血管代謝併發症，如高血壓、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.

需求十分迫切。在美國，阻塞性睡眠呼吸中止症（OSA）影響8,000萬人，其中超過2,000萬人患有中度至重度OSA。我們也知道，絕大多數（約70%）OSA患者同時患有肥胖症。雖然目前已有藥物可以治療OSA相關的白天過度嗜睡，但替澤帕肽有望成為第一個針對OSA根本病因的藥物。

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 evaluated 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 研究由兩項獨立試驗組成，這兩項試驗均遵循相同主方案。研究 1 評估了替唑帕肽在目前未接受正壓通氣（PAP）治療的患者中的療效，而研究 2 評估了替唑帕肽在研究開始前至少 3 個月已接受 PAP 治療且計劃在整個試驗期間繼續接受 PAP 治療的患者中的療效。這兩項研究共納入 469 名受試者。每項研究將受試者隨機分配至替唑帕肽最大耐受劑量組（10 毫克或 15 毫克）或安慰劑組。所有患者均接受 52 週的治療追蹤。

On Slide 13, we show the results of Study 1. For the efficacy estimand 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.

在第13張投影片中，我們展示了研究1的結果。在平均呼吸暫停低通氣指數（AHI）療效評估方面，與安慰劑組相比，替澤帕肽組的平均AHI降低了27.4次/小時，而安慰劑組的平均AHI僅降低了4.8次/小時。這一差異具有高度統計意義。 AHI基線值為52.9，替澤帕肽組的AHI降低了55%。此外，我們也觀察到替澤帕肽治療組的平均心率降低了18.1%，這與我們對研究的預期一致。當然，與安慰劑組相比，這項結果也具有統計意義。

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.

在第14張投影片中，我們展示了研究2的結果。在該族群中，就療效評估指標而言，與安慰劑組相比，替澤帕肽組的平均呼吸暫停低通氣指數（AHI）降低了30.4次/小時，而安慰劑組的平均AHI僅降低了6.0次/小時。替澤帕肽組的基線AHI為46.1，平均AHI降低了62.8%。此外，我們再次觀察到了顯著的體重減輕，平均體重較基線降低了20.1%。所有這些結果均具有高度統計意義。

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.

兩項研究的整體安全性與先前報告的SURMOUNT和SURPASS試驗結果相似。最常見的不良事件為胃腸道相關不良事件，且通常為輕度至中度。接受替澤帕肽治療的患者中最常見的胃腸道不良事件為腹瀉、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，我們注意到投資者對替澤帕肽研究中觀察到的減重效果有疑問，因為研究涉及多種獨特的因素。首先，研究的主要目的並非治療肥胖症。其次，研究族群中約70%為男性，而男性使用腸促胰素類藥物減重可能較為困難。第三，該族群的基線BMI值特別高。最後，研究採用了10毫克或15毫克的最大耐受劑量方案。因此，儘管研究族群本身就難以治療，但我們欣慰地看到，在兩項研究中，52週時觀察到的減重效果接近20%。

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 21st. Additionally, we plan to submit to the FDA and other global regulatory agencies beginning midyear.

與tirzepatide其他III期研究在52週時間點的結果一致，我們未觀察到體重減輕停滯期。我們將於6月21日在ADA年會上舉辦的研討會上公佈SURMOUNT-OSA研究的詳細結果。此外，我們計劃從年中開始向FDA和其他全球監管機構提交申請。

Moving to the other updates across our portfolio. Slide 15 shows select pipeline opportunities as of April 26th, 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-2 which is evaluating efsitora compared to degludec in adults with type 2 diabetes who are naive to basal insulin.

接下來是產品組合的其他更新。第15張投影片展示了截至4月26日的部分在研項目，第16張投影片則列出了今年的潛在重要事件。我們很高興地宣布，我們每週一次的基礎胰島素藥物efsitora alfa的首個III期臨床研究QWINT-4取得了積極成果。研究評估了efsitora與甘精胰島素在接受每日多次胰島素注射的第二型糖尿病成人患者的療效。未來幾週，我們預計將公佈QWINT-4和QWINT-2的主要研究結果。 QWINT-2研究正在評估efsitora與德谷胰島素在未接受過基礎胰島素治療的第二型糖尿病成人患者的療效。

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

這是 efsitora III 期計畫中 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.

我們後期糖尿病和肥胖症產品線的其他更新包括 EMPACT-MI 研究的結果，該研究顯示，與安慰劑相比，Jardiance 在首次因心臟衰竭住院或全因死亡的時間這一主要複合終點方面，相對風險降低了 10%，但未達到統計學意義。

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.

SURMOUNT-MMO 研究已完成招募，共有超過 15,000 名參與者；此外，針對慢性體重管理的 orforglipron 兩項研究 ATTAIN-1 和 ATTAIN-2 也已完成招募，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，我們現在已經啟動了 TRANSCEND III 期項目，研究 retatrutide 在第 2 型糖尿病的應用。

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藥物lepodisiran的III期臨床試驗。這項研究將評估lepodisiran在改善高脂蛋白A（Lp(a)）水平患者的心血管預後方面的療效，這些患者可能患有心血管疾病或有心臟病發作或中風的風險。我們正在評估lepodisiran在二級預防和高風險族群一級預防的療效。我們希望未來它能為醫療保健提供者提供一種治療選擇，以應對因Lp(a)水平升高而導致心血管風險增加的廣大患者群體。

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.

在我們早期的糖尿病和肥胖症產品線中，我們已經啟動了一項 II 期單藥治療研究，評估我們選擇性胰淀素受體激動劑 eloralintide 在肥胖症中的應用。

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.

轉向腫瘤學領域。在進行中期分析後，我們決定終止評估Verzenio治療轉移性荷爾蒙敏感性前列腺癌的III期臨床試驗CYCLONE-3，理由是試驗療效不佳。繼上季宣布CYCLONE-2研究未達主要終點後，Verzenio在攝護腺癌領域的研發工作至此結束。

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 2nd 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.

在腫瘤早期研發階段，我們已啟動兩項新資產的I期臨床試驗。第一項是我們的Nectin-4抗體偶聯藥物（ADC），該藥物來自我們對Emergence Therapeutics的收購。第二項是PNT2001，該藥物來自我們對POINT Biopharma的收購。我們對腫瘤產品組合的進展感到鼓舞，並預計2024年將會取得豐碩成果。除了Nectin-4 ADC和PNT2001的啟動之外，我們預計今年至少還有三種其他新分子將進入臨床試驗。我們期待在禮來腫瘤團隊主辦的腫瘤領域投資者活動上與投資界分享更多詳情。本次活動將於6月2日（週日）晚間在芝加哥舉行，與美國臨床腫瘤學會（ASCO）年會同期舉辦，並將透過網路直播。我們計劃在活動中介紹我們的腫瘤策略和研發管線進展。有關本次活動的更多詳情將很快公佈。

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.

接下來談談神經科學。上個月，我們宣布FDA計劃召開週邊和中樞神經系統藥物諮詢委員會會議，討論donanemab在早期症狀性阿茲海默症的應用。我們預計此次諮詢委員會會議將於2024年中期舉行，具體日期將在《聯邦公報》上公佈。我們預計會議將重點討論donanemab的安全性和有效性，以及該臨床計畫的獨特之處。我們仍然對donanemab為患者帶來顯著益處的潛力充滿信心，並期待以這種形式回答FDA提出的問題。

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（我們用於治療 2 型戈謝氏症的基因治療資產）的研究。帕金森氏症和 1 型戈謝氏症的 II 期研究仍在進行中，並未受到此決定的影響。

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 at a 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，在免疫學領域，我們已向美國食品藥物管理局 (FDA) 和歐洲藥品管理局 (EMA) 提交了 mirikizumab 的上市申請，用於治療中度至重度活動性克隆氏症成人患者。在美國，我們已重新向 FDA 提交了 lebrikizumab 的上市申請，用於治療中度至重度異位性皮膚炎。此前，FDA 根據對第三方生產商的檢查結果發出了完整的回覆函。需要提醒的是，該函件指出，臨床資料包的安全性和標籤均無任何問題。我們預計監管機構將於今年下半年採取行動。

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.

我們同時宣布，未來幾個月內，我們將啟動 lebrikizumab 在兩項新適應症中的 III 期臨床試驗：慢性鼻竇炎伴隨鼻息肉和常年性過敏原引起的過敏性鼻炎。 Lebrikizumab 將成為第一個進入 III 期臨床試驗評估其治療過敏性鼻炎的生物製劑。我們對 lebrikizumab 在這些患者群體以及異位性皮膚炎治療中成為重要治療選擇的潛力充滿信心。在早期免疫學研發方面，我們已將 CD19 抗體推進至多發性硬化症的 II 期臨床試驗階段。

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

現在我將把電話轉回給戴夫，請他作總結發言。

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 the 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 to sustain our long-term growth outlook.

好的，謝謝丹。在進入問答環節之前，我先簡單總結我們第一季的進展。第一季強勁的營收成長主要得益於我們近期推出的產品，尤其是Mounjaro和Zepbound。我們預計，隨著腸促胰素類藥物供應量的持續成長，下半年營收成長將進一步加速。我們研發管線的重要進展包括：tirzepatide和SURMOUNT-OSA的初步數據公佈；Mounjaro的KwikPen給藥裝置在歐盟獲批；mirikizumab和lebrikizumab的上市申請已提交；以及正如丹剛才提到的，lepodisiran III期臨床試驗已啟動。我們將繼續投資於近期和即將上市的產品、內部和外部的研發管線，以及擴大生產規模，以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.

現在我把電話交給喬，讓他主持問答環節。

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。我們希望盡可能回答來電者的問題，並儘快結束通話。 （接線生指示）

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

保羅，請提供問答環節的說明，我們已經準備好迎接第一位來電者了。

(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克里斯·肖特。

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?

恭喜您的進展。我有個問題，希望您能詳細解釋一下今天上調業績指引背後的產能動態。具體來說，我想了解一下，這次上調是主要針對美國市場還是國際市場？我們應該將其理解為系統產能超出預期，還是僅僅意味著新工廠投產速度加快，而年底整體產能可能與預期持平？

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

謝謝克里斯。接下來我將把麥克風交給阿納特，讓她談談績效指引上調的問題。

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業績指引時所提到的那樣，我們預計產能和供應將在下半年逐步提升，而目前的情況也正是如此。

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. 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, that are all either ramping up or under construction.

再次提醒大家，我們供應鏈中確實有很多節點需要上線或提升產能。目前，我們正在建造或擴建的設施共有六個，包括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，以及我們剛收購的第七個站點，所有這些站點都在擴建或建設中。

And there are multiple nodes across the 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.

整個供應鏈中有多個節點需要投入運營，這需要獲得批准等等，針對的是全年計劃中的三種產品，具體取決於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 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.

現在今年已經過去四個月了，我們對這些產能節點有了更清楚的了解，也更有信心了。舉個例子，KwikPen在歐洲的核准略早於我們的預期，這讓我們對在歐洲推出KwikPen產品更有信心。

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都在這樣做，包括與合作夥伴或合約研發生產機構 (CDMO) 一起提高產能，以及在現有工廠進行投資以盡可能擴大規模或提高產能。所以，這貫穿了我們的整個供應鏈。

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

下一個問題來自富國銀行的莫希特·班薩爾。

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。從劇本趨勢來看，似乎第四季的價格走勢略有下滑。您能對此做些解釋嗎？另外，我們該如何看待全年各季度的價格和銷售變化趨勢？

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。你沒明說，但我猜你指的是Mounjaro和Zepbound，所以我就把麥克風交給派崔克，讓他談談淨價問題。

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，莫希特。在分析 Mounjaro 的定價時，我認為需要考慮到我們在第四季度財報中宣布了 Mounjaro 的一次性調整，該調整金額相當可觀。因此，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.

展望2024年上半年，需要注意的是，我們已於2023年6月30日終止了25美元的優惠卡，但之前使用該優惠卡的患者可繼續享受優惠至2024年6月30日。因此，Mounjaro在2024年上半年可能會有一些優惠。但從今年下半年開始，我們預期Mounjaro的價格也將面臨一些常規的上漲壓力。

The next question is coming from Umer Raffat from Evercore.

下一個問題來自 Evercore 公司的 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"?

我想簡單談談D部分健保的報銷機制，如果可以的話。我的問題是，替澤帕肽是否會被區別對待，以確保獲得D部分健保報銷？像睡眠呼吸中止症這樣的新適應症，是否會被視為一種適用藥物，而不是被歸類為廣義的「減肥藥」？

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

謝謝，烏默。這個問題我去找派崔克問。

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，Umer。我認為，鑑於美國醫療保險和醫療補助服務中心（CMS）在4月初宣布將根據SELECT試驗的結果報銷肥胖合併症的費用，我們也相信，幾週前我們公佈的關於阻塞性睡眠呼吸中止症的新數據，也將納入Medicare Part D的報銷範圍。我們預期其他合併症以及HFpEF（射血分數保留型心臟衰竭）的試驗結果（假設結果積極並獲得批准）以及之後的行動能力-死亡率結局研究也將獲得類似的報銷。

Still, our true north is really to get the TROA, the Treat and Reduce Obesity Act passed, 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.

不過，我們真正的目標仍然是推動《治療與減少肥胖法案》（TROA）通過，我們堅信這只是時間問題，而不是會不會通過的問題。我們認為該法案不太可能在2024年獲得通過，但仍有一線希望。

The next question is coming from Seamus Fernandez from Guggenheim.

下一個問題來自古根漢美術館的謝默斯·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.

好的。丹，我只是想問一下，您在評估了 SURMOUNT II 期 NASH 數據後，對這些數據有何看法？您認為 tirzepatide 在該領域有怎樣的應用前景？或者 retatrutide 是否仍然是推進該領域研究的合適標靶？上個季度的一些評論引發了很多猜測，我想確認一下，也想了解我們什麼時候能看到這些數據。我記得好像是在 EASL 上公佈，但能否再次確認一下？

Dan?

擔？

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

謝謝，Seamus。那我就先說最後一部分吧。是的，摘要已被接收，將於六月初在EASL會議上發表。屆時大家將有機會看到這項二期臨床試驗的完整NASH研究資料。

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.

正如我們在上次電話會議中所說，數據確實令人振奮。我們分享了一些主要結果。我認為替澤帕肽可能對這種疾病產生深遠的影響。這是一項二期臨床試驗。下一步是與FDA討論替澤帕肽的最佳後續研發路徑。

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 on 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，您也指出，我們還有另一個選擇－瑞他曲肽（retatrutide）。根據早期研究的生物標記數據，瑞他曲肽也可能對這種疾病產生顯著療效。該分子添加了升糖素，這可能對肝臟有額外的益處。因此，當我們與監管機構進行討論時，這些都是重要的機會和有益的選擇。

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 這類疾病，就像其他與肥胖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，為患者研發出最好的藥物。

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

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

You showed a slide, Zepbound has NBRx share market of 57% at 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.

您展示了一張投影片，Zepbound 在第一季末的 NBRx 市佔率為 57%。這清楚地表明，最強的藥物才能勝出。關於這一點，您能否談談即將公佈的競爭對手數據，以及它們在減重和血糖指標方面與 Zepbound 的對比情況？具體來說，就是諾和諾德的 CagriSema 和安進的 133。我知道這只是最佳猜測，但這是我們被要求做的。

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

謝謝，蒂姆。好的。我或許會請丹發表一些意見。

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.

當然可以，提姆。雖然推測競爭對手的數據可能是你的工作，但我既然問了，就試著說說吧。關於AMG 133，我們目前掌握的數據還非常有限。所以一切都有可能，相信你也會對他們的結果感興趣。當然，關於GIP激動劑和拮抗劑的作用機制，也存在一些爭議。我們已經做出了選擇，而且我們對目前獲得的GIP激動劑數據比較滿意。

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，對於 CagriSema 而言，在 GLP-1 的基礎上增加對不同路徑的作用是明智之舉。 tirzepatide 就是這樣一種雙重激動劑。因此，CagriSema 的研發是合理的。您也會注意到，我們的胰淀素激動劑已進入 II 期臨床試驗。

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，瑞他曲肽已經是三重激動劑。禮來公司或許還有更多潛力可以挖掘。我認為，在我們目前處於I期和II期臨床試驗階段的產品組合中，有九種藥物被認定用於治療糖尿病或肥胖症。其中許多藥物預計在現有機制的基礎上進一步減輕體重，此外還有兩種藥物處於III期臨床試驗階段。因此，我們擁有強大的產品組合。我認為替澤帕肽在減重方面仍然具有無可比擬的療效，但我們也積極研發下一代藥物。

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

下一個問題將來自摩根士丹利的特倫斯·弗林。

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.

恭喜你們取得的所有進展。我想問一下，IQVIA的處方數據是否準確反映了替澤帕肽的實際用量？考慮到LillyDirect通路的用量以及你們對該通路用藥量的了解，IQVIA的數據是否被低估了？如果數據被低估了，能否請你們幫我們量化一下低估的程度？

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。關於IQVIA和LillyDirect，我請派崔克來點評一下。

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。就LillyDirect而言，我們對目前的開局非常滿意。從消費者的使用情況來看，它正以每週為單位穩定成長。

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交易量數據，特別是Zepbound的數據，會發現透過LillyDirect的交易量相對較低，而NBRx的交易量略高一些。據我們了解，IQVIA預設不會記錄通過LillyDirect的交易量。但IQVIA也有自己的方法來估算透過LillyDirect的交易量。

The next question will be from Akash Tewari from Jefferies.

下一個問題將來自傑富瑞集團的阿卡什·特瓦里。

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?

您的團隊去年在ADA會議上展示了GIP單藥激動劑的數據，但現在看來，您正計劃將胰淀素推進到II期臨床試驗。您能否談談為什麼胰淀素可能比GIP更適合作為肥胖症的維持治療方案？您的產品在半衰期和對降鈣素及胰淀素的優先激動作用方面，與其他產品相比有何優勢？

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

謝謝你，阿卡什。接下來請丹將我們的胰淀素講解。

Yes, there are a lot of good questions in there. Thanks for following the science 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，這裡面有很多好問題。感謝您如此密切地關注科學研究。關於GIP這種長效分子，我認為在那項實驗中，我們主要是想展示單獨使用GIP激動劑的益處，以解答一些關於替澤肽作用機制的問題。但正如您所指出的，這種分子在其他適應症方面具有潛力，也可以作為單藥療法或與其他機制的藥物聯合使用。

But of course, since tirzepatide already includes GIP agonism, we're also excited to explore other mechanisms. So that's where the lara, 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，由於替澤帕肽本身就包含GIP激動劑作用，我們也對探索其他機制充滿熱情。正如我剛才提到的，我們正在探索的9種不同機制之一——長效胰淀素——已進入II期臨床試驗。它或許可以作為聯合療法、維持療法或單藥療法，還有很多值得探索的方向。目前，所有機制的研究都還處於非常早期的階段。因此，我們將繼續投入研發，並在獲得數據後及時分享。

The next question will be from Trung Huynh from UBS.

下一個問題將來自瑞銀集團的 Trung Huynh。

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?

最近我剛了解到，CMS擴大了Wegovy的醫療覆蓋範圍，使其適用於某些心臟疾病。我很欣賞您提到TROA是主要目標。但您認為Zepbound也會像Wegovy一樣被納入CMS的健保範圍嗎？這大概什麼時候會發生？是在第三季心臟衰竭數據公佈之後嗎？還是我們需要等到CVOT資料出來？

Thanks, Trung. I'll let Patrik respond.

謝謝，Trung。我請Patrik來回覆吧。

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，Trung。根據CMS四月初的說法，我們預期Zepbound上市時，阻塞性睡眠呼吸中止症的適應症就能獲得CMS和Medicare的報銷。接下來，如果HFpEF的檢測結果積極並獲得批准，那麼下一個適應症就是HFpEF。第三個適應症是MMO（多發性骨髓瘤）。這就是我們的計劃順序，前提是一切按計劃進行，並且我們都能獲得這兩項適應症的批准。

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

下一個問題將來自美國銀行的傑夫·米查姆。

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?

我知道你們之前肯定被問過這個問題，但能否解釋為什麼只在歐洲等美國以外的市場使用KwikPen？我不明白為什麼它不能應用於美國市場，以及這是否也能成為未來緩解產能壓力的手段？

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

謝謝傑夫的提問。戴夫，你想發表一下看法嗎？

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。伊利亞還可以補充一點。正如我們在之前的幾次電話會議中提到的，我們的目標是全面推進上述所有方案，尤其是在供應方面，因為我們意識到巨大的需求和尚未滿足的需要，以及供應鏈規模化所面臨的限制。 KwikPen 利用現有資源，因此減少了時間延遲。我們首先在英國，現在在歐洲推廣這種模式，以滿足患者的需求。但我們並未排除在其他地區推廣的可能性。因此，我們將繼續探索各種方案，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.

下一個問題來自貝倫貝格銀行的凱莉·霍爾福德。

I'm going to take a different topic here. Looking at 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.

我接下來要談另一個話題。關於你們的新產品LP(a)，你們提到現在正在推進III期臨床試驗。請問你們是否已經公佈了新的II期臨床試驗數據？我還沒找到。如果我沒記錯的話，大概什麼時候才能看到這些數據公佈？另外，能否確認一下你們在III期臨床試驗中所採用的劑量和給藥頻率？我猜你們目前在同類產品中排名第三，我很想了解一下你們的藥物與已經進入III期臨床試驗的競爭對手相比，有哪些差異化優勢。

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，Kerry。這是一個很好的多部分問題，關於Lp(a)，我很樂意討論lepodisiran。 Dan，你對此有什麼看法嗎？

Yes. Thanks, Kerry, for the good questions here. You're right, we haven't yet published the 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, Phase II data in hand and use that to design and begin the Phase III trial.

是的。謝謝Kerry提出的好問題。你說得對，我們還沒有公佈二期臨床試驗數據。但我想我們最近才公佈了一期臨床試驗數據。這真的令人振奮，而且反應很好。我認為大家在一期臨床試驗數據中註意到的一點是，單次注射lepodisiran後，其作用時間非常長，並且能顯著降低Lp(a)水平。當然，我們現在已經掌握了二期臨床試驗數據，並將以此為基礎設計並啟動第三期臨床試驗。

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.

我認為我們尚未完全公佈劑量或給藥頻率，但我相信隨著時間的推移，我們會公佈的。您問到了差異化的問題。我認為，與目前均處於 III 期臨床試驗階段的短效 ASO 和 siRNA 相比，我們可能存在幾種不同的差異化優勢。首先，Lp(a) 的清除深度可能有所不同。我們目前尚不清楚 Lp(a) 需要降低多少才能帶來心血管獲益，也不清楚是否有門檻效應或下限。因此，清除深度是其中一個面向。

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 in this Phase III study.

第二個方面，如您所問，可能是給藥頻率或作用持續時間，這兩者密切相關。第三個方面當然是研究人群。我注意到我們在這裡研究的是二級預防和一級預防。所以我認為我們擁有一個不錯的方案，其中包含多種差異化機會，並且我們渴望在這項 III 期研究中驗證 Lp(a) 假說。

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

下一個問題將來自TD Cowen公司的Steve Scala。

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?

鑑於根據所有現有指標，SURPASS-CVOT 中期評估可能已經結束，您能否確認，試驗終止的唯一原因是存在生存獲益或療效不佳，而不僅僅是非劣效性？根據您目前掌握的信息，您對最終達到優效性有何信心？

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

謝謝，史蒂夫。丹，你想回答關於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，我們盡量不對中期分析發表評論，儘管我們許多不同的試驗都包含中期分析。但正因如此，當我們談到風險，例如無意中揭盲結果時，我們更傾向於不予置評。

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.

您說得對，這項研究的主要分析和設計都圍繞著非劣效性展開，我們目前已知該藥物是一種能有效降低心血管風險的非常有效的藥物，那就是Trulicity。所以，它被設計成一項非劣效性試驗。當然，最終數據出來後，我們更希望看到它具有優效性。

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.

您問及我們的信心。我們對此次公佈的數據信心持續增強。事實上，正如今天事先準備好的發言稿中所述，我們甚至從阻塞性睡眠呼吸中止症（OSA）研究中獲得了更多數據，這應該會讓我們更加確信，不僅是睡眠呼吸中止症的益處（這本身就可能帶來心血管益處），還有體重減輕的效果。我認為，不同人群、不同試驗以及男性、女性等族群在體重減輕方面存在一些擔憂。而此次發表的數據消除了部分疑慮。因此，我們仍然充滿信心，並期待研究完成後獲得相關數據。

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

下一個問題來自 BMO 資本市場的 Evan Seigerman。

I wanted to touch on donanemab with the AdCom approaching. Can you discuss 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.

我想在諮詢委員會即將召開之際談談donanemab。您能否談談您對該藥物的信心是否有所改變？以及您希望在與這些外部專家的討論中重點關注哪些方面。

Thanks, Evan. Anne, you want to discuss the donanemab AdCom?

謝謝，埃文。安妮，你想討論多納內單抗的諮詢委員會嗎？

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 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，它能為早期症狀性阿茲海默症患者帶來顯著的益處，而且我們對整個方案的核准前景也充滿信心。我們期待收到問題，目前還沒收到。我認為我們預計討論的重點將圍繞donanemab的安全性和有效性。其安全性和有效性與我們已發表和展示的資訊非常一致，所以這方面沒有什麼新的進展。

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.

我們的試驗有幾個獨特之處，我們預期他們會想討論。其中之一是限時給藥。我們認為這是多納單抗的一個極其重要的特點，即在斑塊清除後可以停止給藥。多納單抗能夠強效且快速地清除斑塊，因此我們認為這使得限時給藥方案成為可能。我們非常期待取得相關數據，並希望顧問們能夠看到這些數據並回應。

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.

另一個獨特之處在於對基線tau蛋白水平進行評估。這對於我們了解tau蛋白這一預後因素至關重要，而我們也確實做到了。但我們在試驗中觀察到，所有患者無論tau蛋白水平如何均獲益，其中疾病早期患者的益處更為顯著。這也是我們對TRAILBLAZER-3試驗充滿信心的原因之一。雖然Dan在發言中沒有提及，但我認為，基於我們在早期人群（tau蛋白水平低或tau蛋白陰性，但生物標記結果卻非常顯著）中觀察到的結果，我們對更早進行幹預的機會更加充滿信心。我想您可能還記得，在我們研究的早期階段，患者的病情進展減緩了60%。我們相信，隨著研究的深入，在臨床前期患者中，這種減緩效果可能會更加明顯。

But maybe just one remark. In the meantime, though, this is not time losy. 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 theAdcom, as Dan said, in mid-'24 and answering any questions that they have.

但或許我只想補充一點。同時，我們不會浪費時間。我們將繼續確保醫療系統做好準備。我們將確保在獲得潛在批准後，進入一個更強大的市場。因此，我們正在充分利用這段時間，並期待像丹所說的那樣，在2024年年中與審批委員會見面，回答他們提出的任何問題。

Next question will be from David Risinger from Leerink Partners.

下一個問題將來自 Leerink Partners 的 David Risinger。

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?

首先，我要祝賀你們的進展以及業績指引的上調。我的問題是關於orforglipron的。鑑於orforglipron生產的複雜性，諾和諾德對其產能可擴展性提出了一些擔憂。我沒有直接與諾和諾德溝通，但有人告訴我，他們提到該藥物的生產過程有35個步驟。我不知道這是否屬實。能否請您談談禮來公司是如何擴大其產能的？該公司是否預計在2026年上市後能夠滿足西方國家的全球需求？或者，我們投資界是否應該預料到供應限制，並在預測orforglipron上市後的產能爬坡時保持謹慎？

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

謝謝，戴夫。接下來交給我們的戴夫·里克斯。

Okay. Great. Dave, great to hear from you. I mean, first of all, it is true that orforglipron is a complicated 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。太好了。戴夫，很高興收到你的來信。首先，奧福格列酮確實是一種複雜的小分子，或者說，如果你非要說的話，它是一種“大分子”，而且它的合成過程涉及很多步驟。我想你可以在我們的專利申請文件中找到相關資訊。

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.

但禮來公司或許與其他公司不同，我們生產小分子藥物已經很久了。我們有能力做到這一點。我們知道如何將它們組合在一起，而且我們已經有了一套成熟的工藝流程來生產奧福格列酮。

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，儘管原料藥的生產過程漫長且可能比其他小分子藥物更為複雜，但我們對此充滿信心，並且完全掌握了相關技術。與注射劑相比，成品加工流程才是真正的重大進步，因為我們只需進行片劑沖壓或片劑膠囊製造，這些都是我們非常熟悉的乾式工藝。

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.

我認為最大的優勢在於，無論是合成化學、膠囊製造或錠劑製造，地球上都已具備相當可觀的產能。因此，與我們之前討論的注射劑領域不同，我們需要在註射劑領域新建產能，正如Anat之前提到的，我們正在積極推進這項工作。在這個領域，我們擁有眾多合作夥伴，以及我們自身龐大的乾粉製劑和原料藥生產網絡。所以我對此非常有信心。

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.

我們能否在每種情況下都精準控制劑量和用量？我們無法保證，但如果奧福格列酮在 III 期臨床試驗中被證實安全有效，我認為情況將會大不相同。再次強調，III 期臨床試驗將在 2025 年進行，因此我們預期該藥物將在一年後上市，這對腸促胰素類藥物的發展歷程而言意義重大。

Next question is coming from Louise Chen from Cantor.

下一個問題來自 Cantor 公司的 Louise Chen。

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

我只是想問您關於下一批肥胖症藥物的情況。看起來您有六種藥物正在研發中。您認為您最大的優勢在哪裡？

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

丹，你想談談早期肥胖症嗎？

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 improve 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。我們對早期肥胖症分子藥物組合感到非常興奮。我認為即使是像替澤帕肽這樣優秀的藥物，也還有許多改進的空間。我們認為減重的品質是一個重要面向。例如，即使使用替澤帕肽，我們也觀察到隨著患者體重減輕，瘦體重與脂肪的比例也會改善。我們能否利用像比馬格魯單抗這樣的肌肉刺激劑，讓這比例更快改善呢？這或許正在研究中。

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.

替澤帕肽耐受性良好，但有些人會因為胃腸道副作用而停止服用。我們能否研發出副作用較少的藥物呢？或許可以。替澤帕肽每週注射一次，大多數患者都能接受。但如果減少注射頻率，或許可以減輕生產負擔，也方便患者使用。這又是另一個值得探索的方向。

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.

有些患者即使服用像替澤帕肽這樣強效的藥物，也無法達到理想的減重效果。因此，這又是另一種治療途徑。

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

最後，針對不同的適應症，例如我之前提到的與代謝性疾病相關的MASH，不同的藥物活性可能對這些相關疾病的療效有所不同。這是另一個鑑別診斷的途徑。

I think we're just at the beginning of probably what will be seen as a multi-decade investment 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.

我認為我們目前所處的階段可能只是未來幾十年治療代謝異常及其相關疾病的長期投資的開端。我非常自豪和欣慰的是，禮來公司在該領域擁有業內最強大的研發管線。

The next question is from Chris Shibutani from Goldman Sachs.

下一個問題來自高盛的克里斯·澀谷。

Wanted to ask about the supply and demand dynamic 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?

我想問一下供需動態以及兩者何時可能趨於平衡的問題。 Anat，你之前用詞很具體，說過這種情況可能會在2025年發生。 Dave，當你之前在我們接待的一個小組面前發言時，我覺得你給的範圍更廣一些。鑑於你們目前取得的所有進展，例如收購威斯康辛州的工廠等等，關於供需動態何時可能趨於平衡，你有什麼最新的消息想和大家分享？

Thanks, Chris. Anat?

謝謝，克里斯。安娜特？

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 to make sure we're progressing rapidly as you've seen evidenced by the results as well as the raise we did for the year.

是的，讓我先從這一點說起。正如我在事先準備好的發言稿中所說，我們預期短期和中期內供需情勢仍將相當緊張。需要澄清的是，我們並非面臨生產問題。我們的生產設施進展非常順利，我為全球M&Q同事們的工作感到無比自豪。顯然，我們的生產基地全天候運轉，連夜加班加點。我們正在進行正確的投資，以確保我們能夠快速發展，正如你們從業績和年度加薪中所看到的那樣。

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 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.

但市場需求強勁，考慮到這些產品能為患者帶來許多健康益處，它們都是高效且安全的藥物，這一點並不令人意外。我預計，即使我們大幅提升了產能，並且增加了不同劑型（包括自動注射器和速效筆）的供應，這種強勁的需求仍將持續到今年年底。即便如此，我預計今年的需求仍將超過供應。當然，明年可能會有所變化，我們拭目以待。我們將繼續投資並擴大產能，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，如果III期臨床試驗結果積極，這將為我們提供一種新的解決方案，就像Dave提到的那樣，我們可以利用我們全球生產組織現有產能中的不同基礎設施，提供不同的劑型。因此，我們將分階段推進。我們將持續向投資者報告進度，並貫穿今年及未來幾年。

Next question will be from Carter Gould from Barclays.

下一個問題將來自巴克萊銀行的卡特·古爾德。

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 期數據公佈之前深入了解 bimagrumab。您能否談談在所有體重減輕驅動因素中展現統計意義或清晰的劑量反應的重要性，以及在考慮是否進入 III 期臨床試驗時，避免整體體重減輕效果減弱的重要性？

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

謝謝卡特的提問。丹，你想對bimagrumab發表一下看法嗎？

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 or an increased ratio, I should say, of lean to fat mass by combining bimagrumab with incretins.

是的，謝謝卡特。問得好。 Bimagrumab 的減重機制與腸促胰素截然不同，但我們認為它與腸促胰素合併使用可能非常重要。因此，我們認為 bimagrumab 可能對脂肪組織和肌肉量都有顯著影響。所以我們希望透過將 bimagrumab 與腸促胰素合併使用，能夠增加肌肉量，或者更準確地說，提高瘦體重與脂肪的比例。

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 incretins. Looking forward to seeing that data.

在本研究中，我們將評估該藥物作為單藥療法以及與不同劑量的索瑪魯肽合併用藥的效果。我們將觀察其對脂肪組織的減重效果是否疊加，以及在先前的比馬格魯單藥治療研究中觀察到的對瘦體重的影響是否能與腸促胰素合併使用。期待看到相關數據。

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?

祝賀你們取得的所有進展。我有一個關於你們放射性藥物研發管線的問題。你們提到了腫瘤藥物研發管線中的PNT2002。能否談談你們對該專案進度的看法？根據目前的情況，你們認為它在市場佔有率方面會處於什麼位置？

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

謝謝Kripa的提問。 Jake，打電話給你，是想請你對我們的放射性配體研究，特別是PNT2001，發表一些意見嗎？

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，很樂意。謝謝你的提問。我們非常高興能透過收購 POINT Biopharma 將放射性藥物納入產品組合，同時我們也透過自身的研發實驗室和自主生產能力，進一步拓展業務。因此，除了 PNT2001 之外，我預計在未來幾年內，我們將有更多關於其他藥物的消息可以分享。

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.

但具體到這個問題，2001 是一種針對前列腺癌的 PSMA 標靶療法，它與 α 發射體錒偶聯。我認為，錒相比镥更有前景，尤其是在產生雙股 DNA 斷裂而非單股 DNA 斷裂方面，以及可能提高攝護腺癌患者的療效。我認為現有藥物的限制之一是它們可能對唾液腺造成過大的毒性，因此難以成為真正持久有效的產品。

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的PSMA靶向配體，與唾液腺相比，該配體在腫瘤中的攝取量更高，從而利用錒作為有效載荷來提高治療指數。目前我們才剛開始I期臨床試驗，所以暫時還不能透露太多。但臨床前研究結果非常令人矚目，與其他現有的PSMA配體截然不同。我們期待它順利完成I期臨床試驗，最後獲得理想的結果。

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.

根據臨床特徵，我認為對於已經接受過镥基藥物治療的患者，這種療法有可能改善治療效果；或許可以先於镥基藥物使用，與镥基藥物競爭，甚至可能更早地用於治療，因為PSMA表達確實貫穿於前列腺癌的整個治療過程。隨著我們在I期臨床試驗中明確臨床特徵，我們將對此進行更多探討。

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，我想我們或許還有時間再問一個問題。現在已經11點了。所以，這或許是待問的最後一個問題了。

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詹姆斯‧申。

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

我只是想嘗試解釋一下，指導劑量上調與維持 1.5 倍可售劑量之間的關係。

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。詹姆斯，或許我應該讓阿納特談談指導意見，以及指導意見的提高與1.5倍劑量相關的評論有何關係。

So let's start with the 1.5 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.

那麼，我們先從我在二月的指導電話會議上提到的1.5個可售劑量說起。這裡指的是可售劑量，而不是設備數量。隨著KwikPen產能的提升，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選擇。

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.

那條評論指的是今年下半年與去年下半年的對比。因此，我們預計今年下半年的總可售劑量至少是去年下半年的1.5倍。這一點保持不變。但我們對推進每個即將上線或核准產能節點的信心，等等，都顯著提升了。今年會有多個這樣的節點。其中一些已經發生。還有一些將會發生，像是我剛才提到的KwikPen。

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 at least 1.5.

例如，想想我們在北卡羅來納州康科德的工廠建設，我們之前說過它將在年底前投入運營，明年就能看到產品下線。現在工廠已經完工，生產線也已安裝完畢，接下來我們需要進行資格認證、獲得批准等等。我們自己的生產基地以及外部工廠都有多個類似的節點，所有這些節點都需要上線運行，才能達到我們全年業績預期目標。隨著時間的推移，我們的信心有所增強，但目前仍維持在至少1.5倍的水平。

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Anat。太好了。感謝各位今天抽空參加今天的財報電話會議，也感謝你們對我們公司的關注。如果您還有其他今天未解答的問題，請聯絡投資者關係團隊。祝您今天過得愉快。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.

謝謝大家。女士們、先生們，今天的會議到此結束。本次會議將於今天下午1點開始提供回放，並持續到6月4日午夜。您可以隨時撥打(800) 332-6854並輸入接取碼317750收聽回放。國際用戶請撥(973) 528-0005。感謝您的參與。您可以掛斷電話了。