禮來公司 (LLY) 2023 Q3 法說會逐字稿

Ladies and gentlemen, thank you for standing by, and welcome to the Lilly Q3 2023 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 2023 年第三季財報電話會議。 （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。

Good morning, and thank you, Paul. And thanks, everybody, for joining us for Eli Lilly and Company's Q3 2023 Earnings Call. I'm Joe Fletcher, Senior Vice President of Investor Relations. And joining me on today's call are Dave Ricks, Lilly's Chair and CEO; Anat Ashkenazi, Chief Financial Officer; Dr. Dan Skovronsky, Chief Scientific and Medical Officer; Anne White, President of Lilly Neuroscience; Ilya Yuffa, President of Lilly International; Jake Van Naarden, President of Loxo at Lilly; Mike Mason, President of Lilly Diabetes and Obesity; and Patrick Johnson, President of Lilly Immunology and Lilly USA. We're also joined by Michaela Irons, Mike Springnether and Lauren Zierki of the IR team.

早安，謝謝你，保羅。感謝大家參加禮來公司 2023 年第三季財報電話會議。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，首席科學和醫療官； 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；麥克梅森 (Mike Mason)，禮來公司糖尿病與肥胖部總裁；以及禮來免疫學和禮來美國公司總裁 Patrick Johnson。 IR 團隊的 Michaela Irons、Mike Springnether 和 Lauren Zierki 也加入了我們。

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 3. Additional information concerning factors that could cause actual results to differ materially is contained in our latest Form 10-K and subsequent Forms 10-Q and 8-K filed with the Securities and Exchange Commission.

在本次電話會議中，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（包括幻燈片3 中列出的因素），實際結果可能會存在重大差異。有關可能導致實際結果存在重大差異的因素的更多資​​訊包含在我們最新的表格10-K 以及後續提交的表格10-Q 和8-K 中。證券交易委員會。

The information we provide about our products and pipeline is for the benefit of the investment community. It's not intended to be promotional and is not sufficient for prescribing decisions. As we transition to our prepared remarks, please note that our commentary will focus on non-GAAP financial measures.

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。當我們轉向準備好的評論時，請注意，我們的評論將重點放在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。

Thanks, Joe. In Q3, Lilly continued the progress we made so far this year. We delivered strong financial results, continue to advance our R&D pipeline and invested in our future through several business development transactions. As you can see on Slide 4, we continue to make progress against our strategic deliverables this quarter.

謝謝，喬。在第三季度，禮來公司繼續了我們今年迄今的進展。我們取得了強勁的財務業績，繼續推進我們的研發管道，並透過多項業務發展交易投資於我們的未來。正如您在投影片 4 中所看到的，我們本季的策略交付成果持續取得進展。

Excluding revenue from the olanzapine portfolio and COVID-19 antibodies, revenue grew 24%. Our new products and growth products combined contributed approximately 17 percentage points toward volume growth, with over 12 percentage points coming from our growth products.

不包括奧氮平產品組合和 COVID-19 抗體的收入，收入增加了 24%。我們的新產品和成長型產品合計對銷售成長貢獻了約 17 個百分點，其中超過 12 個百分點來自我們的成長型產品。

Last week, we announced that the FDA approved Omvoh for the treatment of moderately to severely active ulcerative colitis in adults. This marks Lilly's first approval in the U.S. for a type of inflammatory bowel disease, and it's important for Lilly's growth in its immunology portfolio. In addition to the FDA approval for Omvoh, we had several other important pipeline updates since our last earnings call. Specifically, Jardiance was approved by the FDA for the treatment of adults with chronic kidney disease at risk of progression. And we reported positive Phase III results from the VIVID-1 trial, which evaluated the safety and efficacy of mirikizumab for the treatment of adults with moderately to severely active Crohn's disease.

上週，我們宣布 FDA 批准 Omvoh 用於治療成人中度至重度活動性潰瘍性結腸炎。這標誌著禮來公司在美國首次批准治療一種發炎性腸道疾病，這對於禮來公司免疫學產品組合的成長非常重要。除了 FDA 批准 Omvoh 之外，自上次財報電話會議以來，我們還獲得了其他幾項重要的產品線更新。具體而言，Jardiance 已獲得 FDA 批准用於治療有進展風險的慢性腎臟病成人患者。我們報告了 VIVID-1 試驗的積極 III 期結果，該試驗評估了 mirikizumab 治療中度至重度活動性克隆氏症成人的安全性和有效性。

In Q3, we announced that the FDA issued a complete response letter for lebrikizumab based on inspection findings at a third-party manufacturer. The letter stated no concerns with the clinical data package, the safety or the label. We will continue to work with the third-party manufacturer and the FDA to test the findings to make lebrikizumab available to patients as quickly as possible. In terms of business development. We once again had a very active quarter. In Q3, we completed the divestiture of the olanzapine portfolio, which will further enable us to focus on our current and new product launches. The financial impact of this transaction is reflected in the Q3 results.

在第三季度，我們宣布 FDA 根據第三方製造商的檢查結果對 lebrikizumab 發出了完整的回覆函。該信函表示對臨床資料包、安全性或標籤不存在任何擔憂。我們將繼續與第三方製造商和 FDA 合作測試研究結果，以便盡快為患者提供 lebrikizumab。在業務發展方面。我們再次度過了一個非常活躍的季度。第三季度，我們完成了奧氮平產品組合的剝離，這將使我們能夠進一步專注於當前和新產品的發布。此次交易的財務影響反映在第三季的業績中。

Additionally, within the quarter, we completed the acquisition of 2 clinical stage companies adding to our Phase II portfolio, DICE Therapeutics and Versanis Bio, as well as the acquisition of Emergence Therapeutics and Sigilon Therapeutics. We also announced that we reached an agreement to acquire POINT Biopharma, which if approved, has the potential to expand our oncology capabilities into next-generation radioligand therapies. And lastly, we distributed over $1 billion in dividends this quarter. On Slide 5, you'll see a list of key events since our Q2 call, including several important regulatory, clinical and other updates we are sharing today.

此外，在本季度內，我們完成了對 2 家臨床階段公司的收購，增加了我們的 II 期投資組合，即 DICE Therapeutics 和 Versanis Bio，以及對 Emergence Therapeutics 和 Sigilon Therapeutics 的收購。我們也宣布達成收購 POINT Biopharma 的協議，如果獲得批准，將有可能將我們的腫瘤學能力擴展到下一代放射性配體療法。最後，本季我們派發了超過 10 億美元的股息。在投影片 5 上，您將看到自我們第二季電話會議以來的關鍵事件列表，包括我們今天分享的一些重要的監管、臨床和其他更新。

Now let me turn the call over to Anat to review our Q3 results.

現在讓我把電話轉給 Anat，回顧一下我們第三季的業績。

Thanks, Dave. Slide 6 summarizes financial performance in the third quarter of 2023. I'll focus my comments on non-GAAP performance. We're pleased with the strong financial performance this quarter, highlighted by continued acceleration of revenue growth, representing robust momentum in our core business.

謝謝，戴夫。第 6 投影片總結了 2023 年第三季的財務業績。我將重點評論非 GAAP 業績。我們對本季強勁的財務業績感到滿意，其中營收成長的持續加速凸顯了我們核心業務的強勁勢頭。

Q3 revenue increased 37% versus Q3 2022. Excluding revenue from the olanzapine portfolio and from the COVID-19 antibodies, revenue increased 24% in Q3. This represents a quarter-over-quarter acceleration revenue growth driven by Mounjaro and the continued strong performance of Verzenio and Jardiance. Gross margin as a percent of revenue increased to 81.7%. Gross margin in the quarter benefited from the divestiture of the olanzapine portfolio, the absence of COVID-19 antibody sales in Q3 2023 and higher realized prices, partially offset by increases in manufacturing expenses. Marketing, selling and administrative expenses increased 12%, primarily driven by higher expenses associated with new product launches and additional indications as well as compensation and benefit costs.

與 2022 年第三季相比，第三季收入成長了 37%。不包括奧氮平產品組合和 COVID-19 抗體的收入，第三季收入成長了 24%。這代表著由 Mounjaro 以及 Verzenio 和 Jardiance 持續強勁表現推動的季度環比加速營收成長。毛利率佔收入的百分比上升至 81.7%。本季的毛利率受益於奧氮平產品組合的剝離、2023 年第三季沒有銷售 COVID-19 抗體以及實現價格上漲，但部分被製造費用的增加所抵消。行銷、銷售和管理費用增加了 12%，主要是由於與新產品發布和其他適應症以及補償和福利成本相關的費用增加。

R&D expenses increased 34%, primarily driven by higher development expenses for late-stage assets and additional investments in early-stage research. This quarter, we recognized acquired IPR&D charges of $2.98 billion, which negatively impacted EPS by $3.29. In Q3 2022 acquired IPR&D charges totaled $62 million or $0.06 of EPS. Operating income decreased 71% in Q3, driven by acquired IPR&D charges, partially offset by higher revenue associated with the divestiture of the olanzapine portfolio. Operating income as a percent of revenue was approximately 6% for the quarter and reflected a negative impact of approximately 31 percentage points attributable to acquired IPR&D charges.

研發費用增加 34%，主要是由於後期資產的開發費用增加以及早期研究的額外投資。本季度，我們確認收購的 IPR&D 費用為 29.8 億美元，這對 EPS 產生了 3.29 美元的負面影響。 2022 年第三季度，收購的 IPR&D 費用總計 6,200 萬美元，相當於每股收益 0.06 美元。由於收購的智慧財產權與研發費用，第三季營業收入下降了 71%，但部分被奧氮平投資組合剝離帶來的收入增加所抵銷。本季營業收入佔收入的百分比約為 6%，反映出收購的智慧財產權與研發費用帶來的約 31 個百分點的負面影響。

Our Q3 effective tax rate was 84.6%. This represents an increase of approximately 74 percentage points compared to the same period in 2022. The increase in the effective tax rate was primarily driven by the nondeductible acquired IPR&D charges incurred this quarter. Other than the impact of acquired IPR&D, the underlying tax rate was consistent with previously provided guidance. At the bottom line, we delivered earnings per share of $0.10 in Q3, a 95% decrease versus Q3 2022, inclusive of an increase of $1.22 of EPS associated with the divestiture of the olanzapine portfolio and a negative impact of $3.29 from the acquired IPR&D charges.

我們第三季的有效稅率為 84.6%。與 2022 年同期相比增加了約 74 個百分點。有效稅率的增加主要是由本季度產生的不可抵扣的收購智慧財產權費用所推動的。除收購的智慧財產權和研發的影響外，基本稅率與先前提供的指導一致。從底線來看，我們第三季的每股收益為0.10 美元，與2022 年第三季相比下降了95%，其中包括與奧氮平投資組合剝離相關的每股收益增加1.22 美元，以及收購的智慧財產權和研發費用帶來的3.29 美元的負面影響。

On Slide 8, we quantify the effect of price, rate and volume and revenue growth. This quarter, U.S. revenue increased 21%. When excluding revenue from the olanzapine portfolio and COVID-19 antibodies, U.S. revenue grew 32%, driven by robust growth of Mounjaro, Verzenio and Jardiance. Net price in the U.S. increased 13% for the quarter, driven by Mounjaro Access and Saving Cards dynamics. Excluding Mounjaro, net price in the U.S. decreased by high single digits. As mentioned in prior earnings calls, we expected that Mounjaro Access and Saving Card dynamics to have a meaningful impact on reported U.S. price changes in the second half of 2023, which was evident in Q3.

在投影片 8 中，我們量化了價格、費率、數量以及收入成長的影響。本季度，美國營收成長 21%。在排除奧氮平產品組合和 COVID-19 抗體的收入後，在 Mounjaro、Verzenio 和 Jardiance 強勁增長的推動下，美國收入增長了 32%。在 Mounjaro Access 和 Saving Cards 動態的推動下，本季美國的淨價格成長了 13%。不包括Mounjaro，美國的淨價下降了高個位數。正如先前的財報電話會議中所提到的，我們預計 Mounjaro Access 和 Saving Card 動態將對 2023 年下半年報告的美國價格變化產生有意義的影響，這在第三季度很明顯。

Europe continued to post robust growth again this quarter. Excluding revenue from the olanzapine divestiture, revenue was up 7% in constant currency, driven by volume growth of 11% primarily from Verzenio, Jardiance and Taltz. For Japan, Q3 revenue decreased 16% in constant currency. Excluding Mounjaro, which had a onetime upfront payment associated with the sales collaboration agreement in the base period, revenue in Japan decreased 3% in constant currency, driven primarily by customer buying patterns related to Emgality.

本季歐洲持續保持強勁成長。不包括奧氮平剝離帶來的收入，以固定匯率計算，收入成長了 7%，這主要得益於 Verzenio、Jardiance 和 Taltz 銷量成長 11%。對於日本，以固定匯率計算，第三季營收下降了 16%。不包括基期內與銷售合作協議相關的一次性預付款的 Mounjaro，日本的收入按固定匯率計算下降了 3%，這主要是受到與 Emgality 相關的客戶購買模式的推動。

Moving to China. Revenue increased 20% in constant currency with volume growth of 25% partially offset by price declines. Volume growth in Q3 was driven by Tyvyt and Verzenio. We're encouraged by the growth we have seen this year in China, revenue in the rest of the world increased 23% in constant currency as volume growth of 28% was driven by Mounjaro, Verzenio and Jardiance.

搬到中國。以固定匯率計算，營收成長 20%，銷量成長 25%，部分被價格下降所抵銷。第三季銷售成長由達伯舒 (Tyvyt) 和 Verzenio 推動。我們對今年在中國看到的成長感到鼓舞，世界其他地區的營收以固定匯率計算成長了 23%，而 Mounjaro、Verzenio 和 Jardiance 推動了 28% 的銷售成長。

Slide 9 shows the contribution to worldwide volume growth by product category. As you can see, the new products and growth product categories combined contributed approximately 17 percentage points of volume growth for the quarter. The absence of revenue from COVID-19 antibodies compared to the base period was a headwind of nearly 6 percentage points to volume in Q3. This headwind will abate as COVID-19 antibody sales were minimal after the third quarter of 2022.

投影片 9 按產品類別顯示了對全球銷售成長的貢獻。正如您所看到的，新產品和成長產品類別合計為本季銷售成長貢獻了約 17 個百分點。與基期相比，COVID-19 抗體收入的缺失導致第三季銷售量下降了近 6 個百分點。由於 2022 年第三季之後 COVID-19 抗體銷售量極小，這一不利因素將會減弱。

Lastly, revenue from the sales of rights of the olanzapine portfolio delivered nearly 22% points of growth this quarter. Slide 10 provides additional perspective across our product categories. First, I would like to highlight Verzenio, which saw worldwide sales growth of 68% in Q3, driven by robust volume growth. The continued positive momentum is driven by the early breast cancer indication, with steady performance in the metastatic indication.

最後，本季奧氮平產品組合權利銷售收入實現了近 22% 的成長。幻燈片 10 提供了我們產品類別的更多視角。首先，我想強調 Verzenio，在銷售強勁成長的推動下，第三季全球銷售額成長了 68%。持續的積極勢頭是由早期乳癌適應症推動的，在轉移適應症方面表現穩定。

Jardiance continued its strong 2023 performance, with worldwide revenue growth of 22% for the quarter. As you heard earlier in Q3, Jardiance was approved by the FDA for the treatment of adults with chronic kidney disease at risk of progression. In Q3, we saw worldwide Trulicity revenue declined 10% as volume growth in the U.S. was more than offset by lower prices, driven by changes to estimates for rebates and discounts in both periods as well as unfavorable segment mix and higher contracted rebates. In international markets, Trulicity volume continues to be affected by measures we have taken to minimize potential disruption to existing patients, including communications to health care professionals, not to start new patients on Trulicity.

Jardiance 持續保持 2023 年的強勁業績，該季度全球營收成長 22%。正如您在第三季早些時候聽說的那樣，Jardiance 已獲得 FDA 批准用於治療有進展風險的慢性腎臟病成人患者。第三季度，我們看到Trulicity 全球收入下降了10%，因為美國銷量的成長被價格下降所抵消，這是由於兩個時期的回扣和折扣預估變化以及不利的細分市場組合和較高的合約回扣所致。在國際市場，Trulicity 的銷售持續受到我們為盡量減少對現有患者的潛在幹擾而採取的措施的影響，包括與醫療保健專業人員的溝通，而不是讓新患者開始使用 Trulicity。

Moving to Slide 11. We continue to be pleased with the strong performance of Mounjaro as more type 2 diabetes patients benefit from the medicine. Mounjaro revenue grew to just over $1.4 billion globally this quarter, up from $980 million the previous quarter. In Q3, we continued to make progress in expanding access to Mounjaro. As of October 1, access for patients with type 2 diabetes in the U.S. reached 78% in aggregate across commercial and Part D, including 85% access for commercial patients.

轉向幻燈片 11。隨著越來越多的 2 型糖尿病患者受益於該藥物，我們仍然對 Mounjaro 的強勁表​​現感到滿意。本季 Mounjaro 的全球營收從上一季的 9.8 億美元增至略高於 14 億美元。第三季度，我們在擴大對 Mounjaro 的訪問方面繼續取得進展。截至 10 月 1 日，美國 2 型糖尿病患者的商業和 D 部分的使用率總計達到 78%，其中商業患者的使用率為 85%。

This expanded access gives more patients the opportunity to start therapy on Mounjaro for type 2 diabetes. As communicated last quarter, since the $25 noncovered co-pay card program expired on June 30, we now consider all prescriptions paid. As a reminder, we define paid scripts as those prescriptions outside of the $25 noncovered co-pay card, but inclusive of the $24 covered co-pay card. We expect Mounjaro net price will continue to benefit from the higher percentage of paid prescriptions, but will also continue to face a headwind from more rebated volume as access improves.

此次擴大進入範圍讓更多患者有機會開始接受 Mounjaro 治療第 2 型糖尿病。正如上季所傳達的，由於 25 美元的非承保共付卡計劃於 6 月 30 日到期，我們現在考慮所有已支付的處方藥。提醒一下，我們將付費處方定義為 25 美元非承保共付卡以外的處方，但包括 24 美元承保共付卡。我們預計 Mounjaro 的淨價將繼續受益於較高比例的付費處方，但隨著准入條件的改善，也將繼續面臨更多回扣量的阻力。

Looking forward to the end of the year. With increased access, we expect to continue to see overall growth in prescription trends. In terms of Mounjaro supply, we're continuing to make progress on our manufacturing expansion agenda. Given strong demand, we continue to experience tight supply throughout most of Q3, which impacted results for the quarter. Most recently, U.S. product shipments have increased and inventory levels of U.S. wholesalers have improved, with all doses of Mounjaro now listed as available on the FDA shortage website.

期待年底的到來。隨著獲取管道的增加，我們預計處方趨勢將繼續整體成長。在 Mounjaro 供應方面，我們正在繼續在製造擴張議程上取得進展。鑑於需求強勁，我們在第三季的大部分時間裡繼續面臨供應緊張的情況，這影響了本季的業績。最近，美國產品出貨量有所增加，美國批發商的庫存水準也有所改善，所有劑量的 Mounjaro 現已在 FDA 短缺網站上列出。

While supply constraints have eased in the U.S. -- outside the U.S., Trulicity and Mounjaro supply is tight, which materially impacted performance in these regions. With device assembly online at RTP, we are on track to achieve our goals of doubling capacity by the end of this year from where we were a year ago and are gradually increasing production each quarter. We're also continuing to focus on other parts of the supply chain as demand is expected to remain high and production bottlenecks may shift over time.

儘管美國的供應限制有所緩解，但在美國以外的地區，Trulicity 和 Mounjaro 的供應仍然緊張，這對這些地區的表現產生了重大影響。透過在 RTP 進行線上設備組裝，我們預計將實現今年年底產能較一年前翻一番的目標，每季的產量都在逐步增加。我們也將繼續關注供應鏈的其他部分，因為預計需求將保持在高位，並且生產瓶頸可能會隨著時間的推移而改變。

As we mentioned in last quarter's earnings call, we are moving forward with different presentation of Mounjaro to reach more patients around the world faster. We have launched with a single dose vial in Australia and plan to launch in other markets outside the U.S. in the coming weeks and months. The introduction of a single dose vial presentation in these geographies is intended to serve as a bridge to a multi-dose click pen, which we expect will be available starting in 2024. We're also preparing for a potential launch of tirzepatide for obesity in the U.S. later this year. Our auto-injector capacity and output continues to increase, and we look forward to bringing tirzepatide to more patients in the months and years ahead.

正如我們在上季度的財報電話會議中提到的，我們正在推進 Mounjaro 的不同介紹，以便更快地接觸到世界各地更多的患者。我們已在澳洲推出單劑量小瓶，並計劃在未來幾週和幾個月內在美國以外的其他市場推出。在這些地區推出單劑量小瓶的目的是作為多劑量點擊筆的橋樑，我們預計多劑量點擊筆將於 2024 年開始上市。我們還準備在以下地區推出用於治療肥胖症的替澤帕肽：今年晚些時候美國。我們的自動注射器容量和產量不斷增加，我們期待在未來幾個月和數年為更多患者帶來替西帕肽。

On Slide 12, we provide an update on capital allocation. In the first 9 months of 2023, we invested nearly $12 billion in our future growth through a combination of R&D expenditures, capital investment and business development outlays. In addition, we've returned nearly $4 billion to shareholders in dividends and share repurchases.

在投影片 12 中，我們提供了資本配置的最新情況。 2023 年前 9 個月，我們透過研發支出、資本投資和業務發展支出，為未來成長投資了近 120 億美元。此外，我們也透過股利和股票回購向股東返還了近 40 億美元。

Slide 13 presents our updated 2023 financial guidance. Guidance for the first 4 line items, including revenue, gross margin percent, marketing and selling and administrative expenses and R&D expense is unchanged. I would note that we are trending towards the higher end of our estimates for gross margin in the top end of our ranges for operating expense categories.

投影片 13 介紹了我們更新的 2023 年財務指引。前 4 個項目的指導，包括收入、毛利率、行銷和銷售、管理費用以及研發費用，沒有變化。我要指出的是，我們的毛利率估計正趨向於營運費用類別範圍上限的較高端。

You'll see that we've updated guidance for acquired IPR&D charges, OID, tax rate and EPS to reflect the inclusion of IPR&D charges for completed transactions through Q3, and year-to-date results and equity investments in GAAP guidance. These updates do not include the effect of potential charges associated with pending or future business development transactions after Q3. We will provide our initial 2024 guidance when we report Q4 results.

您會看到，我們更新了收購的 IPR&D 費用、OID、稅率和 EPS 的指導，以反映在 GAAP 指導中包含第三季度已完成交易的 IPR&D 費用以及年初至今的業績和股權投資。這些更新不包括與第三季之後待決或未來業務開發交易相關的潛在費用的影響。我們將在報告第四季度業績時提供 2024 年初步指引。

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

現在我將把電話轉給 Dan，強調我們在研發方面的進展。

Thanks, Anat. This quarter, we had significant pipeline progress as well as a high volume of activity at the major medical congresses where we presented new data on multiple products across all of our therapeutic areas.

謝謝，阿納特。本季度，我們的產品線取得了重大進展，並且在主要醫學大會上開展了大量活動，在會上我們展示了所有治療領域的多種產品的新數據。

Starting with oncology. Since our last earnings call, we announced top line results from the LIBRETTO-531 study evaluating Retevmo versus physician's choice of multi-kinase inhibitors as an initial treatment for patients with advanced or metastatic RET-mutant medullary thyroid cancer. As we presented at ESMO, the study met its primary endpoint, demonstrating a 72% improvement in progression-free survival compared to cabozantinib or vandetanib. These data should establish Retevmo as the standard of care for the initial systemic treatment of patients with progressive advanced RET-mutant medullary thyroid cancer, and we have work to do to ensure that all of these patients are identified and properly diagnosed.

從腫瘤學開始。自上次財報電話會議以來，我們發表了LIBRETTO-531 研究的主要結果，該研究評估了Retevmo 與醫生選擇的多激酶抑製劑作為晚期或轉移性RET 突變型甲狀腺髓樣癌患者的初始治療的情況。正如我們在 ESMO 上介紹的那樣，該研究達到了主要終點，表明與卡博替尼或凡德他尼相比，無惡化存活期提高了 72%。這些數據應將 Retevmo 確立為進行性晚期 RET 突變型甲狀腺髓樣癌患者初始全身治療的護理標準，我們還有工作要做，以確保所有這些患者都得到識別和正確診斷。

We also shared detailed data from the Phase III LIBRETTO-431 Study at ESMO in October, showing that Retevmo more than doubled progression-free survival compared to chemotherapy plus pembrolizumab, in patients with advanced or metastatic RET fusion-positive non-small cell lung cancer. We hope these data, in addition to others recently published for other driver positive lung cancers, will help accelerate genomic profiling at lung cancer diagnosis to guide initial treatment selection.

我們也分享了10 月在ESMO 進行的III 期LIBRETTO-431 研究的詳細數據，顯示對於晚期或轉移性RET 融合陽性非小細胞肺癌患者，與化療加派姆單抗相比，Retevmo 使無進展生存期延長了一倍以上。我們希望這些數據，以及最近發布的其他驅動陽性肺癌的數據，將有助於加速肺癌診斷的基因組分析，以指導初始治療選擇。

The results of LIBRETTO-531 and of LIBRETTO-431 were each simultaneously published in the New England Journal of Medicine. Also at ESMO, we shared landmark 5-year results for a preplanned interim analysis of the Phase III monarchE study evaluating Verzenio in combination with endocrine therapy, compared to endocrine therapy alone, in patients with HR-positive HER2-negative node-positive early breast cancer at a high risk of recurrence. The impact of 2 years of Verzenio treatment is observed well beyond the treatment period, reducing the risk of long-term recurrence by 32% at 5 years. These data reinforce 2 years of Verzenio plus endocrine therapy as the standard of care for high-risk early breast cancer patients.

LIBRETTO-531和LIBRETTO-431的結果分別同時發表在《新英格蘭醫學雜誌》。同樣在ESMO，我們分享了對III 期MonarchE 研究進行預先計劃的中期分析的具有里程碑意義的5 年結果，該研究評估Verzenio 聯合內分泌治療與單獨內分泌治療在HR 陽性HER2 陰性淋巴結陽性早期乳腺癌患者中的比較癌症復發的風險很高。 Verzenio 治療 2 年的效果在治療期結束後仍可觀察到，5 年時長期復發的風險降低了 32%。這些數據強化了 2 年 Verzenio 合併內分泌治療作為高風險早期乳癌患者的照護標準。

Lastly, we shared data on imlunestrant, our oral SERD being studied in Phase III as a single agent and in combination therapy. The data shared included the first clinical data for imlunestrant in combination with everolimus or alpelisib as well as updated monotherapy from the Phase I AMBER study in patients with ER-positive HER2-negative advanced breast cancer. We hope imlunestrant could be an important future endocrine therapy backbone in certain settings of breast cancer. And these new data show that medicine can be safely combined with other agents utilized with endocrine therapy in advanced breast cancer.

最後，我們分享了有關 imlunetrant 的數據，我們的口服 SERD 正在 III 期研究中作為單一藥物和聯合治療。共享的數據包括 imlunetrant 與依維莫司或 alpelisib 聯合用藥的首個臨床數據，以及針對 ER 陽性 HER2 陰性晚期乳癌患者的 I 期 AMBER 研究的更新單藥治療數據。我們希望 Imlunetrant 能夠成為未來某些乳癌內分泌治療的重要支柱。這些新數據表明，藥物可以安全地與晚期乳癌內分泌治療中使用的其他藥物合併使用。

Looking earlier in our oncology pipeline. We shared preclinical data on 3 of our new pipeline agents at the triple meeting on Molecular Targets and Cancer Therapeutics in October. We shared preclinical data for, first, a highly potent inhibitor of KRAS G12D that is selective against wild-type KRAS. Second, a highly potent in isoform selective pan-KRAS inhibitor, with activity against a broad spectrum of the most common activating KRAS mutations and high selectivity over wild-type HRAS and NRAS. And third, a fully human monoclonal anti-nectin-4 antibody conjugated to a topoisomerase inhibitor. These programs are among the next slate of oncology agents we expect to enter the clinic over the next year. They represent years of focused work to create potentially differentiated molecules against exacting target product profiles.

更早檢視我們的腫瘤學研發管線。我們在 10 月的分子標靶和癌症治療三重會議上分享了 3 種新藥物的臨床前數據。首先，我們分享了一種高效 KRAS G12D 抑制劑的臨床前數據，該抑制劑對野生型 KRAS 具有選擇性。其次，是一種高效的異構體選擇性泛 KRAS 抑制劑，具有針對廣譜最常見的活化 KRAS 突變的活性，並且比野生型 HRAS 和 NRAS 具有高選擇性。第三，與拓樸異構酶抑制劑結合的全人單株抗 nectin-4 抗體。這些項目是我們預計明年進入臨床的下一批腫瘤藥物之一。它們代表了多年來針對嚴格的目標產品概況創建潛在差異化分子的專注工作。

Turning to our diabetes and obesity portfolio. In Q3, we announced the FDA approval of Jardiance for treatment of adults with chronic kidney disease at risk of progression. In the EMPA-KIDNEY phase III trial, Jardiance significantly reduced the risk of kidney disease progression and cardiovascular deaths in adults with CKD. This approval adds to the treatment options for the more than 35 million adults in the U.S. affected by chronic kidney disease.

轉向我們的糖尿病和肥胖症產品組合。在第三季度，我們宣布 FDA 批准 Jardiance 用於治療有進展風險的成人慢性腎臟病。在 EMPA-KIDNEY III 期試驗中，Jardiance 顯著降低了 CKD 成人患者腎臟疾病進展和心血管死亡的風險。此次批准為美國超過 3500 萬患有慢性腎臟病的成年人增加了治療選擇。

Since the last earnings call, we presented results from the SURMOUNT-3 Phase III clinical trial at the Obesity Week Conference in October with the results simultaneously published in Nature Medicine. Also in October, we presented detailed results from the SURMOUNT-4 study at EASD. These results will be subsequently published in a top-tier peer-reviewed medical journal. Data from these Phase III trials of tirzepatide showed that participants achieved up to 26.6% total mean weight loss. The detailed results from these studies clearly show the importance of continued therapy for sustained weight management. And that, if approved, tirzepatide could be an important part of obesity management for those having difficulty maintaining weight loss with diet and exercise alone.

自上次財報電話會議以來，我們在 10 月的肥胖週會議上公佈了 SURMOUNT-3 III 期臨床試驗的結果，該結果同時發表在《Nature Medicine》上。同樣在 10 月，我們公佈了 EASD 的 SURMOUNT-4 研究的詳細結果。這些結果隨後將發表在頂級同行評審醫學期刊上。替澤帕肽的這些 III 期試驗的數據顯示，參與者的整體平均體重減輕高達 26.6%。這些研究的詳細結果清楚地表明了持續治療對持續體重管理的重要性。如果獲得批准，替西帕肽可能成為那些僅靠飲食和運動難以維持減肥的人肥胖管理的重要組成部分。

Our pipeline as shown on Slide 14, now includes a high-dose tirzepatide NILEX in Phase II since we have initiated the study exploring higher doses of tirzepatide in participants with type 2 diabetes and obesity. Earlier in the pipeline, we presented Phase I data on Muvalaplin at the European Society of Cardiology Congress with simultaneous publication in JAMA. Muvalaplin is the first oral agent specifically developed to lower Lp(a) levels. In this Phase I study, Muvalaplin was well tolerated by participants and resulted in dose-dependent lowering of Lp(a) of up to 65%. Muvalaplin is currently in Phase II.

我們的產品線如幻燈片14 所示，現在包括II 期的高劑量替澤帕肽NILEX，因為我們已經啟動了一項研究，探索在2 型糖尿病和肥胖症患者中使用更高劑量的替澤帕肽。在這個過程的早期，我們在歐洲心臟病學會大會上展示了 Muvalaplin 的 I 期數據，並同時在《美國醫學會雜誌》上發表。 Muvalaplin 是第一種專門為降低 Lp(a) 水平而開發的口服藥物。在這項 I 期研究中，參與者對 Muvalaplin 的耐受性良好，導致 Lp(a) 劑量依賴性降低高達 65%。 Muvalaplin 目前處於第二階段。

As shown on Slide 14, we have advanced our SCAP siRNA into Phase I for NASH. We've also completed our acquisition of Versanis and now show bimagrumab in Phase II. We are excited about the potential combination of bimagrumab and tirzepatide. Lastly, we're happy to share that since our last earnings call, the retatrutide TRIUMPH Phase III core registration trials are now all actively enrolling to pursue simultaneous indications for chronic weight management, obstructive sleep apnea and knee osteoarthritis.

如幻燈片 14 所示，我們已將 SCAP siRNA 推進到 NASH 的 I 期。我們也完成了對 Versanis 的收購，現在展示了 bimagrumab 的第二階段臨床試驗。我們對 bimagrumab 和替澤帕肽的潛在組合感到興奮。最後，我們很高興與大家分享，自上次財報電話會議以來，瑞他魯肽TRIUMPH III 期核心註冊試驗現已全部積極入組，以尋求慢性體重管理、阻塞性睡眠呼吸中止症和膝骨關節炎的同時適應症。

Turning to our neuroscience portfolio. The FDA has shared with us that the donanemab review will extend into Q1 2024, needing additional time to complete their review. We've completed submissions in Europe and Japan, and submissions to other global regulatory authorities are either completed or underway. Recently, at the clinical trials in Alzheimer's Disease Meeting, we presented new insights from donanemab development program during a symposium session. As part of this symposium, we shared ARIA data from a pooled analysis that included more than 2,000 participants dosed with donanemab, and explored ARIA-E association across a number of baseline variables, highlighting a few key factors most strongly associated with ARIA risk, including baseline amyloid levels, evidence of a prior bleed and high blood pressure.

轉向我們的神經科學產品組合。 FDA 已與我們透露，多南單抗審查將延長至 2024 年第一季度，需要更多時間來完成審查。我們已經完成了在歐洲和日本的提交，向其他全球監管機構的提交也已完成或正在進行中。最近，在阿茲海默症會議的臨床試驗中，我們在研討會上提出了多南單抗開發計畫的新見解。作為本次研討會的一部分，我們分享了一項匯總分析中的ARIA 數據，該分析包括2,000 多名服用多南單抗的參與者，並探討了ARIA-E 與多個基線變量的關聯，強調了與ARIA 風險最密切相關的幾個關鍵因素，包括基線澱粉樣蛋白水平、先前出血和高血壓的證據。

Interestingly, this data also suggested use of antihypertensives decreased the risk of ARIA. Additionally, we shared analyses from our open-label addendum of over 1,000 patients treated with donanemab. These results included a post-hoc analysis of patients with no brain tow and demonstrated similar or even stronger biomarker results than our main TRAILBLAZER-ALZ 2 study. In a separate post-hoc analysis from the TRAILBLAZER-ALZ Phase III study, related to activities of daily living and independence in people with early symptomatic Alzheimer's disease, we showed that compared to placebo, people treated with donanemab preserved more of their ability to perform many of the items measured, including their ability to make meals, to use appliances, keep appointments, perform past times and be safely left unattended.

有趣的是，這些數據還顯示使用抗高血壓藥物可以降低 ARIA 的風險。此外，我們也分享了對 1,000 多名接受多南單抗治療的患者進行的開放標籤附錄的分析。這些結果包括對無腦患者的事後分析，並證明了與我們的主要 TRAILBLAZER-ALZ 2 研究相似甚至更強的生物標記結果。在TRAILBLAZER-ALZ III 期研究的另一項事後分析中，與早期症狀性阿茲海默症患者的日常生活活動和獨立性相關，我們表明，與安慰劑相比，接受多南單抗治療的患者保留了更多的執行能力測量的許多項目包括他們做飯、使用電器、遵守約會、過去的時間以及安全地無人看管的能力。

We also shared an update on our validation data for our plasma P-tau217 test for identifying amyloid-positive patients, demonstrating robust performance of this immunoassay. We expect to have this test commercially available in a phased approach first, as a laboratory developed test by the end of this year. As you recall, we use plasma PTAO217 to identify presymptomatic individuals for a TRAILBLAZER-ALZ 3 trial. This is an event-driven trial, and we have now recruited a sufficient number of qualifying presymptomatic participants and expect to have efficacy results within 3 years.

我們也分享了用於識別澱粉樣蛋白陽性患者的血漿 P-tau217 測試的驗證數據的更新，證明了這種免疫測定的強大性能。我們預計該測試將首先以分階段的方式投入商業使用，作為實驗室開發的測試，到今年年底。您還記得，我們​​使用血漿 PTAO217 來識別 TRAILBLAZER-ALZ 3 試驗的症狀前個體。這是一項事件驅動的試驗，我們現在已經招募了足夠數量的合格的症狀前參與者，預計在 3 年內獲得療效結果。

We're excited to announce today that our Otoferlin gene-therapy asset from Akouos has begun dosing patients in a Phase I/II trial for hearing loss. In immunology, as Dave noted, we're happy to have FDA approval for Omvoh for the treatment of moderately to severely active ulcerative colitis in adults. This approval offers new hope for patients who are searching for an effective option that can offer rapid and lasting improvements. Omvoh will be approved available to patients in the U.S. in the coming weeks.

今天，我們很高興地宣布，我們 Akouos 的 Otoferlin 基因治療資產已開始在針對聽力損失的 I/II 期試驗中為患者給藥。在免疫學方面，正如 Dave 所指出的，我們很高興 FDA 批准 Omvoh 用於治療成人中度至重度活動性潰瘍性結腸炎。這項批准為正在尋找能夠提供快速和持久改善的有效選擇的患者帶來了新的希望。 Omvoh 將在未來幾週內獲得批准，可供美國患者使用。

We were also excited to have the Phase III readout for this molecule, mirikizumab, in Crohn's disease. In the VIVID-1 Phase III study, mirikizumab met the co-primary in all major secondary endpoints compared to placebo. Mirikizumab demonstrated clinical remission and endoscopic response for patients with moderately to severely active Crohn's disease through 52 weeks. We were thrilled to see that more than half of participants on mirikizumab achieved clinical remission at 1 year, and that robust efficacy was seen in both participants who are naïve to biologic therapy as well as participants who previously failed a prior biologic therapy.

我們也很高興能夠獲得這種分子（mirikizumab）治療克隆氏症的 III 期結果。在 VIVID-1 III 期研究中，與安慰劑相比，mirikizumab 在所有主要次要終點中均達到了共同主要終點。 Mirikizumab 在 52 週內顯示出中度至重度活動性克隆氏症患者的臨床緩解和內視鏡反應。我們很高興地看到，超過一半的 mirikizumab 參與者在 1 年時實現了臨床緩解，並且在未接受過生物治療的參與者以及之前生物治療失敗的參與者中都看到了強勁的療效。

Helping patients achieve long-term clinical remission is a key goal for us in our pursuit of treatments for inflammatory bowel disease. These new data in Crohn's disease build on the high levels of long-term remissions seen with mirikizumab for olive colitis, and help reinforce the differentiation of this important potential medicine. This successful Phase III trial will be the basis of global regulatory submissions for Crohn's disease.

幫助患者實現長期臨床緩解是我們尋求發炎性腸道疾病治療的關鍵目標。這些關於克羅恩病的新數據建立在 mirikizumab 治療橄欖結腸炎的高水平長期緩解基礎上，並有助於加強這種重要的潛在藥物的差異化。這項成功的 III 期試驗將成為克隆氏症全球監管提交的基礎。

As Dave noted earlier, in Q3, we announced that the FDA issued a complete response letter for lebrikizumab based on findings at a third-party manufacturer. In Q3, we completed the acquisition of DICE and now reflect the 2 oral IL-17 assets, DC-853 and DC-806 in Phase I and Phase II of our pipeline, respectively. Additionally, 2 new molecules began Phase II studies in immunology this quarter. First, our CD200R monoclonal antibody, known as ucenprubart for atopic dermatitis; and second, our RIPK1 inhibitor for rheumatoid arthritis. We've removed our BTLA monoclonal antibody agonist from Phase II in our pipeline after the Phase IIa study failed to demonstrate efficacy. Q3 was another productive quarter for R&D at Lilly.

正如戴夫早些時候指出的，在第三季度，我們宣布 FDA 根據第三方製造商的調查結果發布了針對 lebrikizumab 的完整回覆函。在第三季度，我們完成了對 DICE 的收購，現在分別在我們的管道一期和二期中反映了兩種口服 IL-17 資產 DC-853 和 DC-806。此外，本季有 2 個新分子開始了免疫學 II 期研究。首先，我們的 CD200R 單株抗體，稱為 ucenprubart，用於治療異位性皮膚炎；其次，我們的 RIPK1 抑制劑用於治療類風濕性關節炎。在 IIa 期研究未能證明療效後，我們已將 BTLA 單株抗體激動劑從我們的管道中的 II 期中刪除。第三季是禮來公司研發工作又一個有成效的季度。

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。

Thank you, Dan. Before we go to Q&A, let me briefly sum up our progress in the third quarter. This quarter, revenue growth accelerated as our recently launched product portfolio continued to gain momentum, of course, led by Mounjaro. Excluding revenue from the divestiture of the olanzapine portfolio and the sale of COVID-19 antibodies in 2022, revenue grew 24%, driven again by Mounjaro, Verzenio as well as Jardiance.

謝謝你，丹。在進行問答之前，讓我先簡單總結一下我們第三季的進展。本季度，隨著我們最近推出的產品組合繼續獲得動力（當然是在 Mounjaro 的帶領下），營收成長加速。不包括 2022 年奧氮平產品組合剝離和銷售 COVID-19 抗體帶來的收入，在 Mounjaro、Verzenio 和 Jardiance 的推動下，收入增加了 24%。

By continuing to invest in recent and coming launches, late-stage medicines and early phase capabilities as well as in business development, we are confident that we have positioned ourselves for growth now and in the coming years, with the opportunity for continued margin expansion. We achieved meaningful advances in our late-stage pipeline with the FDA approval of Omvoh for the treatment of moderately to severely active ulcerative colitis; as well as Jardiance, for the treatment of adults with chronic kidney disease; and the positive Phase III VIVID-1 results for mirikizumab, for adults with moderately to severely active Crohn's disease.

透過持續投資於最近和即將推出的產品、後期藥物和早期能力以及業務發展，我們相信我們已經為現在和未來幾年的成長做好了準備，並有機會持續擴大利潤率。隨著 FDA 批准 Omvoh 用於治療中度至重度活動性潰瘍性結腸炎，我們在後期研發管線中取得了有意義的進展；以及 Jardiance，用於治療成人慢性腎臟病；以及 mirikizumab 針對中度至重度活動性克隆氏症成人的 III 期 VIVID-1 陽性結果。

Looking forward, we are expecting regulatory responses before the end of the year on our submissions for pirtobrutinib, an accelerated approval in CLL, as well as tirzepatide for obesity. In Q3, we completed several targeted acquisitions intended to bolster our early and mid-stage portfolio. Directly following the quarter, we also announced an agreement to acquire POINT Biopharma, which will further expand our R&D capabilities in oncology. Lastly, we returned over $1 billion to shareholders via the dividend.

展望未來，我們預計監管機構將在今年年底前對我們提交的 pirtobrutinib（CLL 加速批准）以及用於肥胖的 tirzepatide 的申請做出回應。在第三季度，我們完成了幾項有針對性的收購，旨在加強我們的早期和中期投資組合。在本季之後，我們也宣布達成收購 POINT Biopharma 的協議，這將進一步擴大我們在腫瘤學方面的研發能力。最後，我們透過股息向股東返還超過 10 億美元。

A few weeks ago, we announced several leadership changes. Mike Mason, our Executive Vice President and President of Lilly Diabetes and Obesity, will retire from the company at the end of 2023 after 34 years with Lilly. In his current role, Mike has overseen tirzepatide's late-stage development and an unprecedented type 2 diabetes launch. Mike leaves behind an enduring legacy that reflects his deep compassion for patients and his commitment to our people. With this being Mike's last earnings call, I would like to thank him for his many years of outstanding service to Lilly, and wish him the best in his next chapter of life. Patrick Johnson will assume leadership of Lilly Diabetes and Obesity, in addition to his current responsibilities as President of Lilly USA. And Dan Skovronsky, our Chief Scientific Officer and President of Lilly Research Labs, will take on the additional role of President of Lilly Immunology from Patrick.

幾週前，我們宣布了幾項領導層變動。我們的執行副總裁兼禮來公司糖尿病和肥胖部總裁 Mike Mason 將於 2023 年底從公司退休，此前他在禮來公司工作了 34 年。在目前的職位上，Mike 負責監督替西帕肽的後期開發和史無前例的 2 型糖尿病上市。麥克留下了一份不朽的遺產，反映了他對病人的深切同情和對我們人民的承諾。這是麥克的最後一次財報電話會議，我要感謝他多年來為禮來公司提供的出色服務，並祝他在人生的下一個篇章中一切順利。除了目前擔任禮來美國總裁的職責外，帕特里克·約翰遜還將領導禮來糖尿病和肥胖部門。我們的首席科學官兼禮來研究實驗室總裁 Dan Skovronsky 將接替帕特里克擔任禮來免疫學總裁。

And in a related move, David Hyman, is assuming the role of Chief Medical Officer for the company from Dan, overseeing the full Lilly portfolio. Leigh Ann Pusey, our Executive Vice President for Corporate Affairs and Communications, has decided to leave the company at the end of 2023. Leigh Ann has left a lasting impact on Lilly and the patients we serve, and we're grateful for her many contributions over the past 6 years.

在一項相關舉措中，大衛·海曼 (David Hyman) 從丹 (Dan) 手中接任該公司首席醫療官，負責監督禮來 (Lilly) 的整個產品組合。我們負責公司事務和傳播的執行副總裁 Leigh Ann Pusey 決定於 2023 年底離開公司。Leigh Ann 對禮來公司和我們服務的患者留下了持久的影響，我們感謝她做出的許多貢獻過去6年。

So as we begin this new chapter of growth for our company, we are very confident that our deep experience of our leadership team will allow us to continue to accelerate our efforts to make medicines and be more effective and more innovative in the years ahead.

因此，當我們開啟公司發展的新篇章時，我們非常有信心，我們的領導團隊的豐富經驗將使我們能夠在未來幾年繼續加快藥品製造步伐，變得更加有效和更具創新性。

So now let me turn the call over to Joe, and he'll moderate the Q&A session.

現在讓我把電話轉給喬，他將主持問答環節。

Thanks, Dave. We'd like to take questions from as many callers as possible and conclude the call in a timely manner. (Operator Instructions) As we'll aim to end the call at 10 a.m. (Operator Instructions) So Paul, please provide the instructions for the Q&A session, and we're ready for the first caller.

謝謝，戴夫。我們希望回答盡可能多的來電者的問題並及時結束通話。 （操作員說明）由於我們的目標是在上午 10 點結束通話。（操作員說明）Paul，請提供問答環節的說明，我們已準備好迎接第一個來電者。

(Operator Instructions)

（操作員說明）

And the first question today is coming from Tim Anderson from Wolfe Research.

今天的第一個問題來自沃爾夫研究中心的蒂姆·安德森。

I have a question on obesity and persistence on therapy, which I think has been a big question, Mark. I know you have normally launched yet, but guessing you might have some idea, a best guess, if nothing else. So in your view, is this going to be like most other drug categories where persistence on therapy is often low? I think the rule of thumb is that at the 1-year mark, 50% of patients drop off chronic medicines. So really, the question, if you took 100 patients who start on one of these contemporary obesity drugs, how many of the initial 100 would likely still be on therapy, let's say, 3 or 4 or 5 years down the road?

我有一個關於肥胖和堅持治療的問題，我認為這是一個大問題，馬克。我知道你通常已經啟動了，但我猜你可能有一些想法，一個最好的猜測，如果沒有別的的話。那麼在您看來，這是否會像大多數其他藥物類別一樣，治療持久性通常較低？我認為經驗法則是，在一年後，50% 的患者放棄慢性藥物治療。所以，真正的問題是，如果你讓100 名患者開始使用其中一種現代肥胖藥物，那麼最初的100 名患者中有多少人可能仍在接受治療，比如說，3 年、4 年或5 年後？

Thanks, Tim. Mike, would you like to weigh in on the persistence of therapy on obesity?

謝謝，蒂姆。麥克，您想談談肥胖治療的持久性嗎？

Yes. Thanks for the question. Maybe I'll first answer with the data that we do have, because it's hard to speculate on what it's going to be for obesity. The best data we have for tirzepatide is in type 2 diabetes patients, who started Mounjaro, prior to our savings card changes last fall. Mounjaro persistency for those patients is tracking higher than those patients that were started on Trulicity and Ozempic over that same period of time. So while it's too early to project the average length of therapy or how many out of 100 will still be on therapy after a couple of years. I think this early data is encouraging.

是的。謝謝你的提問。也許我會先用我們現有的數據來回答，因為很難推測肥胖的影響。我們掌握的替西帕肽的最佳數據來自於 2 型糖尿病患者，他們在去年秋天我們的儲蓄卡變更之前開始使用 Mounjaro。這些患者的 Mounjaro 持久度高於同期開始使用 Trulicity 和 Ozempic 的患者。因此，現在預測平均治療時間或 100 人中有多少人在幾年後仍在接受治療還為時過早。我認為這個早期數據令人鼓舞。

As for obesity, time is going to tell. I think we've all looked at Wegovy data. But I don't think this is the right benchmark at this point because of Novo supply constraints. And there's been just a very dynamic market. I think as you said, this -- having persistency on a chronic treatment isn't just an issue for anti-obesity medications, it's a goal for all treatments. I think what's different about obesity is that on many chronic treatments, consumers don't feel differently are experiencing any acute impacts from [stopping] treatments. So what we've seen in the SURMOUNT clinical trials with tirzepatide is that some consumers will feel their appetite increase and experience weight regain when they stop tirzepatide. And so this should help reinforce treatment adherence.

至於肥胖，時間會證明一切。我想我們都看過 Wegovy 數據。但由於 Novo 的供應限制，我認為目前這不是正確的基準。而且市場非常活躍。我認為正如你所說，堅持長期治療不僅是抗肥胖藥物的問題，也是所有治療的目標。我認為肥胖的不同之處在於，在許多慢性治療中，消費者對於[停止]治療所遭受的任何急性影響並沒有什麼不同的感覺。因此，我們在替澤帕肽的 SURMOUNT 臨床試驗中看到，一些消費者在停止替澤帕肽後會感到食慾增加，體重反彈。因此這應該有助於加強治療的依從性。

Seeing in our market research, how important it is for people who live with obesity to lose weight and maintain it, I do think you're going to see just a high motivation. I see people have lost weight that they do want to maintain it. And we do know our SURMOUNT program that chronic use of tirzepatide is a good component, an important component of maintaining weight loss. So it's too early to project it, but I do think there's things that's rolling in favor of tirzepatide having a good length of therapy in the obesity patients.

從我們的市場研究來看，對於肥胖症患者來說，減肥並保持體重有多麼重要，我確實認為您會看到很高的動機。我看到人們已經減肥了，但他們確實想保持體重。我們確實知道我們的 SURMOUNT 計劃表明，長期使用替西帕肽是一個很好的組成部分，是維持體重減輕的重要組成部分。因此，現在預測還為時過早，但我確實認為，有些事情正在有利於替西帕肽在肥胖患者中獲得良好的治療時間。

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. Thanks so much for the question. So I really wanted to drill into orforglipron and those Phase III programs. Dan, I was just hoping that you could clarify for the market if there's any metering in that study related to liver enzyme elevation. I think there was one case in the Phase II diabetes study that you conducted. Just wanted to know if there's any related concerns associated with that? Or if this is kind of as expected and an all-hands on deck moving forward opportunity?

偉大的。非常感謝您的提問。所以我真的很想深入研究 orforglipron 和那些 III 期計畫。丹，我只是希望你能為市場澄清該研究中是否有任何與肝酵素升高相關的計量。我認為你們進行的二期糖尿病研究中有一個案例。只是想知道是否有任何與之相關的問題？或者這是否符合預期並且是一個全體員工齊心協力前進的機會？

Thanks, Seamus. Yes, I like the way you phrase it, all hands on deck moving forward. On orforglipron, we're really excited about this molecule. In terms of liver safety, I think we commented before that what we saw in Phase II is what we thought would probably be typical for the trial of that nature in this population. So not a heightened level of concern, but always concerned about safety going into Phase III from a variety of factors, including for all small molecules, especially liver function. So it's routine in our Phase III studies across the portfolio to monitor liver function, and I'm sure we're doing that in orforglipron, but not aware of any special precautions there. So super excited that program is going fast.

謝謝，西莫。是的，我喜歡你的措辭方式，所有人齊心協力向前邁進。在 orforglipron 上，我們對這種分子感到非常興奮。就肝臟安全性而言，我認為我們之前評論過，我們在第二階段看到的情況可能是該族群中這種性質試驗的典型情況。因此，並不是高度關注，而是始終關注各種因素進入 III 期的安全性，包括所有小分子，尤其是肝功能。因此，在我們整個產品組合的 III 期研究中，監測肝功能是常規做法，我確信我們正在 Orforglipron 中這樣做，但不知道那裡有任何特殊的預防措施。非常興奮，計劃進展得很快。

The next question is from Terence Flynn from Morgan Stanley.

下一個問題來自摩根士丹利的特倫斯·弗林。

Great. Anat, you had mentioned shifting the date of your 2024 guidance call to early next year. Just want to know what drove that change? And if you can assure us that there are no issues with the tirzepatide obesity review and/or manufacturing.

偉大的。 Anat，您曾提到將 2024 年指導電話會議的日期推遲到明年初。只是想知道是什麼推動了這種改變？如果您可以向我們保證，替西帕肽肥胖症審查和/或製造沒有問題。

Sure. So let me first start with reassuring you that there are no issues behind our decision to move the guidance date to or have it aligned with our Q4 earnings call. What it does do is it does help us have the year-end full results when we provide guidance for 2024. So previously, if we didn't have that, investors had to look at guidance range for the year and estimates based on midpoint, et cetera. This does enable us to close the year and then have a full view into 2024. It is aligned with our internal planning processes as well. And obviously, is the way most companies, and I believe all companies in our industry do that. So nothing unique going into that other than just having the full data set for 2023.

當然。因此，首先讓我向您保證，我們決定將指導日期推遲或與我們的第四季度財報電話會議保持一致，這背後沒有任何問題。它的作用是，當我們提供 2024 年指導時，它確實有助於我們獲得年終完整業績。因此，以前，如果我們沒有這一點，投資者就必須查看當年的指導範圍和基於中點的估計，等等。這確實使我們能夠結束這一年，然後對 2024 年有一個全面的了解。它也與我們的內部規劃流程保持一致。顯然，這是大多數公司的方式，我相信我們行業的所有公司都這樣做。因此，除了擁有 2023 年的完整資料集之外，沒有什麼獨特之處。

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。

Great. And my question is regarding the P-tau217 biomarker data you have shown at [CTAD]. It seems like the predictability is getting to 94% with these tests, ever (inaudible) was pretty good. So do you have any thoughts on, at this point, how close are we to actually make this -- bring this to prime time? And when the donanemab gets approved, do you think this could be the test doctors use or it would still take some time to get to?

偉大的。我的問題是關於您在 [CTAD] 上顯示的 P-tau217 生物標記數據。這些測試的可預測性似乎達到了 94%，（聽不清楚）非常好。那麼，此時此刻，我們離真正實現這一目標還有多遠——將其推向黃金時段，你有什麼想法嗎？當多納奈單抗獲得批准後，您認為這可能是醫生使用的測試，還是仍然需要一些時間才能實現？

Thanks, Mohit, for the question. You broke up a little bit there, but I think we got the gist. I'll hand off to Anne.

謝謝莫希特提出的問題。你們在那裡有點分手，但我想我們已經明白了要點。我會把事情交給安妮。

Yes. As we shared at CTAD, we were pleased with the data that we saw. And we're also pleased to see progress across the field in blood biomarkers. We definitely believe that this is incredibly important to drive access and early diagnosis in Alzheimer's disease. So you've seen us invest in a number of fronts, our own P-tau217, but also partnering with others who are working on good tests to elevate the area. So it's a strategy of raising all boats.

是的。正如我們在 CTAD 上分享的那樣，我們對所看到的數據感到滿意。我們也很高興看到血液生物標記領域的進展。我們堅信，這對於推動阿茲海默症的獲取和早期診斷非常重要。因此，您已經看到我們在許多方面進行了投資，包括我們自己的 P-tau217，而且還與其他致力於良好測試以提升該領域的人合作。所以這是一個舉手之勞的策略。

But yes, we did share our data, and we intend to make this available in a phased approach commercially as an LDT starting at the end of this year in a couple of sites and then continuing to expand over 2024. But at the same time, you'll see us continue to publish the data. We think that what's incredibly important in the field is that good correlative data, particularly with amyloid PET, which is the gold standard in diagnosis, is published and shared. So that we can continue to make sure that we have high-quality tests out there. So that's part of our goal with delivering this test is to really set a standard for what blood test should look like. So look forward to hearing more over the next coming months as we publish that data and then make that more broadly available.

但是，是的，我們確實分享了我們的數據，並且我們打算從今年年底開始在幾個站點以 LDT 的形式分階段將其商業化，然後在 2024 年繼續擴展。但與此同時，您將觀看到我們繼續發布數據。我們認為，該領域極其重要的是良好的相關數據，特別是澱粉樣蛋白 PET（診斷的黃金標準）的發布和共享。這樣我們就可以繼續確保我們擁有高品質的測試。因此，我們提供此測試的目標的一部分是真正為血液檢查設定一個標準。因此，期待在接下來的幾個月中聽到更多信息，因為我們將發布這些數據，然後將其更廣泛地提供。

Next question is coming from Louise Chen from Cantor.

下一個問題來自 Cantor 的 Louise Chen。

I want to ask you, do you think the approval of additional oral potential approval of additional oral diabetes drug could impact pricing for injectables? Why or why not?

我想問您，您認為額外口服糖尿病藥物的額外口服潛在批准的批准會影響注射劑的定價嗎？為什麼或為什麼不？

Thanks, Louise, for the question. I'll hand over to Mike about the potential proof of other oral diabetes drugs and, I guess, potential impact on injectables.

謝謝路易絲的提問。我將向麥克介紹其他口服糖尿病藥物的潛在證據，以及我猜對注射劑的潛在影響。

No, I don't think that will have an impact. I mean, traditionally, we don't see a new class of diabetes agents coming in. And in fact, a current class, usually, the competition happens within a Pacific class within the diabetes market.

不，我認為這不會產生影響。我的意思是，傳統上，我們沒有看到新一類糖尿病藥物的出現。事實上，目前類別的競爭通常發生在糖尿病市場的太平洋類別內。

The next question is from Geoff Meacham from Bank of America.

下一個問題來自美國銀行的 Geoff Meacham。

Thanks for the question. Just had one on tirzepatide supply. I know you guys have a plan in North Carolina and another one coming online next year. But if you look beyond that, if you have demand anywhere near what's modeled, and even outside of obesity and diabetes, obviously, supply could remain tight. So the question, is there a threshold of treated patients like in the near term that will inform your decision on adding manufacturing capacity? And how much does the outlook for orforglipron have on that?

謝謝你的提問。剛剛服用了一份替澤帕肽供應。我知道你們在北卡羅來納州有一個計劃，另一個計劃將於明年上線。但如果你看得更遠，如果你的需求接近模型，甚至在肥胖和糖尿病之外，顯然，供應可能仍然緊張。那麼問題是，是否存在像近期那樣的治療患者閾值，可以為您決定增加生產能力提供依據？ Orforglipron 的前景有多大？

Thanks, Geoff, for the question. I'll hand over to Dave.

謝謝傑夫提出的問題。我將把工作交給戴夫。

Yes. Thanks, Geoff. Obviously, a hot topic. We work on this multiple hours every day. You're citing the announcements we've made. And we've made, as Anat mentioned, great progress the share on manufacturing agenda. RTP sort of on track to deliver on its goal, and as we exit the year. And then that kind of in-market volume following that conquered, which is a few hours away and kind of a replica site. Also, well on track for -- coming online in '24. So that's good news in the (inaudible) presentation, which is the -- what we call our auto injector that you know from Trulicity and the current presentation for Mounjaro in the U.S.

是的。謝謝，傑夫。顯然，這是一個熱門話題。我們每天都在這方面工作好幾個小時。您引用的是我們發布的公告。正如阿納特所提到的，我們在製造議程方面取得了巨大進展。隨著今年的結束，RTP 有望實現其目標。然後，市場上的成交量就征服了，這是幾個小時後的一個複製品網站。此外，預計 24 年上線。所以這是（聽不清楚）演示中的好消息，這就是我們所說的自動注射器，您從 Trulicity 了解到，以及 Mounjaro 在美國的當前演示。

We've announced previously that we're introducing now a single-use vial presentation ex U.S., so that we aren't basically sitting on approvals and can have patients have access to the medication. That will follow then by a multiuse injector that uses different property, plant and equipment than what we're talking about here. So a couple of things to point out. You're noting kind of new greenfield site expansions, we've rightfully made a big deal out of. We're not done with those. I think you might hear more about that in the future. Of course, we are aggressively planning that and not banking on our (inaudible) to rescue us from this. We think that there is a need to take up parenteral incretin supply pretty dramatically from the current levels, and we plan to do that.

我們之前已經宣布，我們現在將在美國推出一次性小瓶包裝，這樣我們基本上就不會等待批准，並且可以讓患者獲得該藥物。接下來將是一個多用途注射器，它使用與我們在這裡討論的不同的財產、工廠和設備。有幾點需要指出。您注意到了一些新的綠地擴建，我們理所當然地大肆宣傳。我們還沒有完成這些。我想您將來可能會聽到更多相關內容。當然，我們正在積極地計劃這一點，而不是指望我們（聽不清楚）來拯救我們。我們認為有必要在目前的水平上大幅增加腸外腸促胰島素的供應，我們計劃這樣做。

But that will be in a combination of the current syringe-based auto-injector, the vial capacity we've already talked about, the multiuse injector, which will come online sometime next year. And it's a highly efficient play for us because it uses current systems, different ones from the auto-injector. And then there's third-party agreements that have been ongoing in the background. And to point out here, we are not going to only have one, we have a diverse portfolio of third parties, recognizing that the probability of full supply from any one is probably less than one, but buying up as much capacity as available in all those systems.

但這將結合目前基於注射器的自動注射器、我們已經討論過的小瓶容量以及多用途注射器，將於明年某個時候上線。這對我們來說是一種高效的遊戲，因為它使用目前的系統，與自動注射器不同。然後還有一直在後台進行的第三方協議。這裡要指出的是，我們不會只有一個，我們有多元化的第三方投資組合，認識到任何一個供應商完全供應的可能性可能小於一，但會購買盡可能多的可用產能那些系統。

So we've got, I think -- the all hands on deck as used earlier. I mean this is really all hands on deck and it's a problem to work every day. So we're not at all python the capacity we've announced already. You'll see more. Some we don't announce. That will just layer in to the volume we ship. And of course, long term, new presentations like a solid oral opens up even more possibilities. But we need to do everything we can now, given the huge potential for global obesity treatment for our medicines to play a key role in that, and then ultimately impact hundreds of millions of people. So a lot of work to do here yet ahead. Thanks for the question.

所以，我想，我們已經像之前那樣，全體人員齊心協力了。我的意思是，這確實需要所有人齊心協力，每天工作都是一個問題。所以我們根本不是Python我們已經宣布的能力。你會看到更多。有些我們沒有公佈。這將只是分層到我們發貨的數量中。當然，從長遠來看，新的演講（如紮實的口頭演講）開啟了更多的可能性。但考慮到全球肥胖治療的巨大潛力，我們的藥物將在其中發揮關鍵作用，並最終影響數億人，因此我們現在需要竭盡全力。因此，未來還有很多工作要做。謝謝你的提問。

Next question is from Laura Hindley from Berenberg.

下一個問題來自貝倫貝格的勞拉·欣德利 (Laura Hindley)。

So I think it's clear from your results that the mix system for Mounjaro is rapidly in progress. But how should we think about the ex-U.S. Trulicity contribution going forward, which did look weak this quarter? But at the moment, you're still supply restricted. Can we expect a return to growth into next year as constraints ease? Or should we now assume Trulicity is ex-growth as you put the shift into Mounjaro?

所以我認為從你的結果中可以清楚地看出，Mounjaro 的混合系統正在迅速進展。但我們該如何看待美國以外的國家？ Trulicity 的未來貢獻，本季哪些看起來疲軟？但目前，供應仍受到限制。隨著限制的緩解，我們能否預期明年經濟將恢復成長？或者我們現在應該假設 Trulicity 是前成長，因為你將轉變轉移到 Mounjaro 嗎？

Thanks, Laura, for the question. I'll hand over to Ilya Yuffa, President of Lilly International. Ilya, do you want to address Trulicity ex-U.S. contributions in the quarter and going forward?

謝謝勞拉提出的問題。我將把會議交給禮來國際公司總裁伊利亞·尤法 (Ilya Yuffa)。 Ilya，您想寄電子郵件給美國以外的 Trulicity嗎？本季的貢獻以及未來的貢獻？

Sure. Yes, first, thanks for the question. Listen, I think from Trulicity standpoint, we had healthy growth coming into later part of last year, and we've been pretty transparent with both physicians as well as regulators that, due to tight supply, we are encouraged not to start with new patients. We continue with that. To be transparent, we think it's the right thing to do.

當然。是的，首先，謝謝你的提問。聽著，我認為從 Trulicity 的角度來看，我們在去年下半年實現了健康成長，而且我們對醫生和監管機構都非常透明，由於供應緊張，我們鼓勵不要從新患者開始。我們繼續這樣做。為了保持透明，我們認為這是正確的做法。

As we think about the growth in incretin, we're looking as we build up capacity, as David mentioned, as we increase capacity, both in the single-use file and introduce Mounjaro in additional markets, as we have, in Australia and will continue over the next number of weeks and months in other markets, and then transition towards a multi-use platform of Quick Pen in introducing Mounjaro. So the overall growth in incretin will be mainly driven by as we are able to launch Mounjaro in new markets, that's probably where we'll get the growth.

當我們考慮腸促胰素的成長時，我們正在考慮擴大產能，正如David 所提到的，隨著我們增加一次性產品的產能，並將Mounjaro 引入其他市場，就像我們在澳洲所做的那樣，並將在接下來的幾週和幾個月裡，我們將繼續在其他市場進行推廣，然後過渡到 Quick Pen 的多用途平台，引入 Mounjaro。因此，腸促胰素的整體成長將主要由我們能夠在新市場推出 Mounjaro 所推動，這可能是我們將獲得成長的地方。

The next question is coming from Umer Raffat from Evercore.

下一個問題來自 Evercore 的 Umer Raffat。

I realize Mounjaro is not approved in obesity yet, but I'm just very curious how you're thinking about the pros and cons heading into that pricing decision, if there are any? Because Novo does have that price premium, as you know, on Wegovy or Ozempic. So on the one hand, while Mounjaro price could be the same because the dose is the same. But on the other hand, Novo have this dynamic where it can offer a lot more rebate for the obesity indication than you can if you leave the price unchanged. I'm just curious what your thought process is heading into that.

我知道 Mounjaro 尚未被批准用於治療肥胖症，但我很好奇您如何考慮定價決策的優缺點（如果有的話）？因為如您所知，Nov​​o 在 Wegovy 或 Ozempic 上確實有溢價。所以一方面，雖然 Mounjaro 的價格可能是相同的，因為劑量是相同的。但另一方面，Novo 有這樣的動力，它可以為肥胖症提供比保持價格不變更多的折扣。我只是好奇你的思考過程是怎麼樣的。

I'll hand over to Mike.

我將把工作交給麥克。

Yes. Thanks for the question. Obviously, we're not going to talk about price prior to approval. We're evaluating every scenario, and we'll make the right decision for patients who live with obesity.

是的。謝謝你的提問。顯然，我們不會在批准之前談論價格。我們正在評估每種情況，並將為肥胖患者做出正確的決定。

The next question is coming from David Risinger from Leerink.

下一個問題來自 Leerink 的 David Risinger。

Yes. Thanks for all the updates today. So some major payers seem to underappreciate the broad health savings potential that incretins offer the nondiabetic obese population, and instead focus on criticizing drug pricing. So ahead of the results from Mounjaro's morbidity and mortality outcome trial in 2027, how does Lilly plan to better inform payers about Mounjaro's health economics benefits in nondiabetic obese patients?

是的。感謝今天的所有更新。因此，一些主要的支付者似乎低估了腸促胰島素為非糖尿病肥胖者帶來的廣泛的健康儲蓄潛力，而是專注於批評藥品定價。那麼，在 2027 年 Mounjaro 的發病率和死亡率結果試驗結果出來之前，禮來公司計劃如何更好地告知付款人 Mounjaro 對非糖尿病肥胖患者的健康經濟學益處？

Thanks, Dave, for the question. Mike, do you want to talk a little bit about that, about the longer-term appreciation for the broader health benefits of medicines like tirzepatide?

謝謝戴夫提出的問題。麥克，你想談談這個問題，談談對替澤帕肽等藥物更廣泛的健康益處的長期認識嗎？

Yes. No, David, it's a good question, and one that we've obviously spent a ton of time on and done a lot of internal analysis and a lot of planning on. We will have a whole suite of real-world evidence and pragmatic trials so that we answer this question clearly for payers and other stakeholders. In our conversations with payers, while they're concerned about the short-term budget impact, they do understand that losing weight will have benefits. It's not that hard of a sale because they do understand the benefits are intuitive.

是的。不，大衛，這是一個很好的問題，我們顯然花了很多時間，做了很多內部分析和很多規劃。我們將擁有一整套現實世界的證據和務實的試驗，以便我們為付款人和其他利害關係人清楚地回答這個問題。在我們與付款人的對話中，雖然他們擔心短期預算影響，但他們確實明白減肥會帶來好處。銷售並不難，因為他們確實知道好處是直覺的。

If you look at the total number of like obesity rate of complications, there's over 200. And you look at -- some of these are just stating and very costly like type 2 diabetes, coronary heart disease, hypertension, dyslipidemia. And then when you look at the cost of these on the U.S. alone, there's $370 billion in direct medical costs associated with the obesity rate comorbidities and over $1 trillion in indirect annual cost. When payers see that people living with obesity and overweight drive 2.7x to greater health care costs than normal individuals, it does get their attention.

如果你看一下肥胖等併發症的總數，你會發現有超過 200 種。你看，其中一些只是陳述性的，而且代價高昂，例如第 2 型糖尿病、冠心病、高血壓、血脂異常。如果只考慮美國的這些費用，就會發現與肥胖率合併症相關的直接醫療費用達 3,700 億美元，間接年度費用超過 1 兆美元。當付款人看到肥胖和超重患者的醫療費用是正常人的 2.7 倍時，確實引起了他們的注意。

And so I think over time, we'll continue to provide health economics data. But also, I think the voice of those living with obesity will be very important in this. This is a disease that really materially impacts someone's both health and mental functioning, and is really important for people who live with obesity. Their goal is to lose weight and maintain that so they can help their long-term health benefits. And they're going to have a lot of voice in this.

因此，我認為隨著時間的推移，我們將繼續提供衛生經濟學數據。而且，我認為肥胖者的聲音在這方面也非常重要。這是一種對人的健康和心理功能產生真正重大影響的疾病，對於肥胖症患者來說非常重要。他們的目標是減肥並保持體重，這樣才能幫助他們獲得長期的健康益處。他們將在這方面有很多發言權。

I think both commercial insurance as well as in states and the federal government. And so I do -- I am confident over time that we will see increase in access. I think the most recent report shows that there's 50 million people in the U.S. that has access to our obesity medication. So it will take time, but I think I do think more and more payers are appreciating the value that anti-obesity medications, especially when we get approval for tirzepatide, will offer them.

我認為商業保險以及州和聯邦政府都是如此。我也是這麼做的——我相信隨著時間的推移，我們將看到訪問量的增加。我認為最新的報告顯示，美國有 5,000 萬人可以使用我們的肥胖藥物。所以這需要時間，但我認為我確實認為越來越多的付款人正在認識到抗肥胖藥物的價值，特別是當我們獲得替澤帕肽的批准時，它們將提供這些價值。

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

下一個問題來自 BMO 資本市場的 Evan Seigerman。

Congrats on the progress. So given the executive changes announced on in October, how should we think about the direction of the immunology business now with Dan at the helm?

祝賀取得的進展。那麼，考慮到 10 月宣布的高階主管變動，我們該如何思考 Dan 掌舵的免疫學業務的方向？

Thanks, Evan. Dave, do you want to take that?

謝謝，埃文。戴夫，你想接受這個嗎？

Sure, I can start and let Dan comment. We've been really pleased with this business, which I think it's important to take the long view here. I mean I was involved in creating this like 10 years ago in both (inaudible) and now mirikizumab, and hopefully soon, lebrikizumab will form a really core portfolio for us, really exploiting ideas that we had some time ago. What's next and you see here today advancing another checkpoint agonists into Phase II is a lot of decisions about, okay, what's next to take immunology to the next level. And that's largely going to be about key decisions, both internal portfolio and potentially externally, like with our DICE acquisition, to find a new set of either single agent or combinations that can raise the standard of care in tough immunology diseases.

當然，我可以開始讓丹評論。我們對這項業務非常滿意，我認為放眼長遠很重要。我的意思是，我在 10 年前就參與了（聽不清楚）和現在 mirikizumab 的創建，希望很快 lebrikizumab 將為我們形成一個真正的核心產品組合，真正利用我們前一段時間的想法。接下來，您今天在這裡看到，將另一種檢查點激動劑推進到第二階段是很多決定，好吧，接下來要做什麼才能將免疫學提升到一個新的水平。這在很大程度上將涉及關鍵決策，包括內部投資組合和潛在的外部決策，例如我們收購 DICE，以找到一套新的單藥或組合藥物，以提高困難免疫疾病的護理標準。

Noting, in particular, in IBD and RA, the standard of care is hardly satisfied today. We measure pretty low performance status to success. So that's the mission that Dan, and we've hired Mark Genovese to the company and others, to really build the portfolio of the future. So I don't know, Dan, if you want to...

特別值得注意的是，在 IBD 和 RA 領域，如今的護理標準很難令人滿意。我們衡量成功的績效狀態相當低。這就是 Dan 和我們聘請 Mark Genovese 到公司和其他人的使命，真正建立未來的投資組合。所以我不知道，丹，你是否想...

No, really excited about the opportunity. There's lots of work to do in immunology to help unmet medical needs and the science is breaking here. So I hope we can continue to bring great drugs to market as we're doing with mirikizumab, and we hope to do with lebrikizumab soon and more to come.

不，我對這個機會感到非常興奮。為了幫助未滿足的醫療需求，免疫學方面還有很多工作要做，而且科學正在這方面取得突破。因此，我希望我們能夠繼續將優秀的藥物推向市場，就像我們對 mirikizumab 所做的那樣，我們希望很快就能對 lebrikizumab 做同樣的事情，而且還會有更多的藥物上市。

The next question is coming from Chris Schott from JPMorgan.

下一個問題來自摩根大通的克里斯·肖特。

Just as we're thinking about the upcoming tirzepatide obesity approval, just interested in your perspective of how we should anticipate commercial coverage ramping as we think of maybe the first couple of quarters post launch versus where it could be in a year or 2 from now? Just how quickly can we think about coverage coming on board?

正如我們正在考慮即將到來的替西帕肽肥胖症批准一樣，只是對您對我們應該如何預測商業覆蓋範圍擴大的看法感興趣，因為我們認為可能是上市後的前幾個季度，而不是從現在起一兩年後的狀況？我們能多快考慮加入覆蓋範圍？

Thanks, Chris. I'll hand over to Mike to comment on anticipation of commercial coverage over time. Mike?

謝謝，克里斯。我將請麥克評論隨著時間的推移對商業報道的預期。麥克風？

Yes. No, it's a good question. It will ramp up. We'll -- we're trying to be disciplined, and we're trying to make sure that we bring on access as quickly as is prudent. And so just like we did with Mounjaro, we'll take -- and make sure that we sometimes access has to materialize at an organic pace where it makes sense, and we'll make sure and use our judgment. So just like with Mounjaro, while we'd love to get out of the gate quickly, most importantly as a setup for long-term success.

是的。不，這是一個好問題。它會加速。我們會——我們正在努力遵守紀律，我們正在努力確保我們以謹慎的方式盡快提供訪問權限。因此，就像我們對 Mounjaro 所做的那樣，我們將確保有時訪問必須以有意義的有機速度實現，我們將確保並運用我們的判斷。就像 Mounjaro 一樣，雖然我們希望盡快走出困境，但最重要的是作為長期成功的基礎。

So you'll see kind of a natural ramp up that you would with any new product. And I think it's important, as you look in the first quarter of our launch last January, when you saw Wegovy resupply, they were resupplying into a market where they already have capacity. So I think when you look at our access and you look at our volume as we head into next year, you'll see a ramp-up in volume as you see a ramp-up in our access.

因此，您會看到與任何新產品一樣的自然增長。我認為這很重要，正如你在去年一月我們推出的第一季看到的那樣，當你看到 Wegovy 補給時，他們正在向一個已經有能力的市場補給。因此，我認為，當您查看我們的訪問量並查看我們進入明年的數量時，您會發現隨著我們的訪問量增加，您會看到數量的增加。

The next question is from Steve Scala from TD Cowen.

下一個問題來自 TD Cowen 的 Steve Scala。

Question on why Lilly is evaluating higher doses of tirzepatide. There is risk in adverse event is uncovered and taints the franchise. And of course, there are IRA considerations. Does this suggest some reservation about the pipeline, either GGG or orforglipron, the former, which has safety signals, the latter of which took 5 years to get to Phase III? It would also be interesting to know whether it's the exact same molecule or it's been enhanced in some way.

關於為什麼禮來公司正在評估更高劑量的替澤帕肽的問題。不良事件被發現並損害特許經營權是存在風險的。當然，還有 IRA 的考慮因素。這是否顯示對管道有所保留，無論是GGG還是forglipron，前者有安全訊號，後者花了5年才進入三期？了解它是否是完全相同的分子或是否以某種方式得到增強也很有趣。

Thanks, Steve, for the question. Dan?

謝謝史蒂夫提出這個問題。擔？

Okay. I'll take all of that. I think I'm not sure exactly what the safety signals you're referring to on retatrutide, I think -- but we're excited about both reta and orforglipron, which are both in Phase III and both advancing quickly. We've invested quite a lot in those Phase III programs, the robust cover multiple indications. So there's no hesitation or trepidation there at all. I think though not in those 2 molecules, which I expect to be great and important contributors to human health.

好的。我會接受這一切。我想我不確定你所指的瑞他魯肽的安全信號到底是什麼，但我們對 reta 和 orforglipron 感到興奮，它們都處於第三階段，並且進展很快。我們在這些三期計畫上投入了大量資金，涵蓋了多種適應症。所以根本沒有猶豫或恐懼。我認為這不是這兩種分子，我希望它們對人類健康做出巨大而重要的貢獻。

We have tirzepatide. I'm not exactly sure if we've maximized the dose response -- if we hit the flat part of the dose response curve yet. It looked like we might be close, but we want to explore it and so we're testing the higher doses in Phase II. I think we've had enough patients on this drug for long enough that I expect the risk of uncovering a new safety signal with sort of marginally higher doses is extremely low. So not worried about that at all.

我們有替澤帕肽。我不確定我們是否已經最大化了劑量反應——是否達到了劑量反應曲線的平坦部分。看起來我們可能已經很接近了，但我們想要探索它，所以我們正在第二階段測試更高的劑量。我認為我們已經有足夠多的患者使用這種藥物足夠長的時間，因此我預計透過稍高的劑量發現新的安全訊號的風險極低。所以根本不擔心這個。

Maybe just jumping in here as we have questions like this. We have a number of research projects in obesity and related mechanisms. And some people ask, well, how does this one effect that or whatever. That's not really the insight in which we're pursuing this. We're -- we see ourselves a leader in the space and have a unique opportunity. And our goal is to exploit every single idea until we get data that says we shouldn't. And so high dose tirzepatide is just another version of that, but it doesn't have a read-through to other things. We're just in all of the above mode in obesity.

也許只是因為我們有這樣的問題而跳到這裡。我們有許多關於肥胖及相關機制的研究項目。有些人會問，好吧，這會如何影響這一點或其他什麼。這並不是我們真正追求的洞察力。我們認為自己是該領域的領導者，並且擁有獨特的機會。我們的目標是利用每一個想法，直到我們得到的數據顯示我們不應該這樣做。所以高劑量的替澤帕肽只是它的另一個版本，但它沒有對其他東西的通讀。我們只是處於上述所有肥胖模式。

The next question is from Chris Shibutani from Goldman Sachs.

下一個問題來自高盛的 Chris Shibutani。

In about a week or so, we'll get detailed results from the select cardiovascular outcomes trial at the American Heart Meeting. Can you share with us what perhaps 3 key questions that the Lilly team will be looking at when we get detailed results?

大約一週後，我們將從美國心臟會議上選定的心血管結果試驗中獲得詳細結果。您能否與我們分享一下，當我們獲得詳細結果時，禮來團隊可能會考慮哪些 3 個關鍵問題？

Dan, do you want to weigh in on...

丹，你想參與一下...

I don't know. I can start -- maybe Mike has some to add here. Look, I'm excited to see that data, of course, as everyone else is, but the top line looked good. For me, I think we're sort of creating now data points on the line that connect the level of weight loss with the degree of cardiovascular benefit. I think this point fits on that line reasonably well, that in which shows greater health benefits, including better -- fewer MACE outcomes, with greater degrees of weight loss, bodes very well for Mounjaro data, given the very high degrees of weight loss that we saw in our trials. I'll leave it at that. See if Mike wants to add.

我不知道。我可以開始了——也許麥克還需要補充一些內容。看，我當然很高興看到這些數據，就像其他人一樣，但頂線看起來不錯。對我來說，我認為我們現在正在創建數據點，將減肥水平與心血管益處程度聯繫起來。我認為這一點相當符合這條線，這顯示出更大的健康益處，包括更好的——更少的MACE 結果，以及更大程度的體重減輕，這對Mounjaro 的數據來說是個好兆頭，因為體重減輕的程度非常高我們在考驗中看到了。我就這樣吧。看看麥克是否想添加。

Probably the key question I'm looking at is like how much of the effect was driven by drug effect versus weight losses, probably the question we're looking at.

也許我正在研究的關鍵問題是，有多少效果是由藥物效應與體重減輕驅動的，這可能是我們正在研究的問題。

The next question is coming from Carter Gould from Barclays.

下一個問題來自巴克萊銀行的卡特·古爾德。

Congrats on the progress. Maybe following on the prior question, but maybe more on sort of the impact of the flow data and your thoughts there, specifically you guys have taken sort of a different approach with your more recent assets there. In terms of targeting that population, is Lilly's view that those benefits will accrue to the class? And maybe just talk about how you think about targeting that segment down the road.

祝賀取得的進展。也許是在回答前一個問題，但也許更多的是關於流量數據和您的想法的影響，特別是你們對最近的資產採取了不同的方法。就針對該族群而言，禮來公司認為這些好處是否會惠及該階層？也許只是談談您如何看待未來瞄準該細分市場。

Thanks, Carter, for the question. Dan, do you want to comment on the flow data?

謝謝卡特提出的問題。 Dan，您想對流量數據發表評論嗎？

Yes. So you're asking about kidney disease. I mean I think the profound effect that incretin seem to be having on the kidney is really a nice and important additive benefit here. This is something that's been observed with multiple class members now and expect it, it will extend into our incretins as well. So it's exciting, and I think these drugs, perhaps in addition to the weight loss and (inaudible) control could have other direct metabolic benefits, including the kidney.

是的。所以你問的是腎臟疾病。我的意思是，我認為腸促胰島素對腎臟的深遠影響確實是一個很好且重要的附加益處。現在已經在多個班級成員中觀察到了這一點，並且預計它也會延伸到我們的腸促胰素中。所以這很令人興奮，我認為這些藥物除了減肥和（聽不清楚）控制之外，可能還有其他直接的代謝益處，包括腎臟。

The next question is coming from Trung Huynh from UBS.

下一個問題來自瑞銀集團的 Trung Huynh。

Just one on Mounjaro U.S. pricing. So by our calculations, we think at 3Q '23, the net price is around $440 per [TRx]. For the rest of the year, do you think that net price can continue to go up and above the saving card price of $450? Are there payers willing to pay for this? Or is this broadly capped now until that saving card ends? And for next year, can you just give us your thoughts on if net price can meaningfully keep increasing?

只有一份有關 Mounjaro 美國定價的資訊。因此，根據我們的計算，我們認為在 23 年第三季度，每個 [TRx] 的淨價約為 440 美元。在今年剩下的時間裡，您認為淨價會繼續上漲並高於儲蓄卡價格 450 美元嗎？有付款人願意為​​此買單嗎？或者說，在儲蓄卡結束之前，這個上限現在已經被廣泛限制了嗎？對於明年，您能否告訴我們您對淨價是否能夠有意義地繼續成長的想法？

Thank, Trung. Mike, do you want to make any comments around Mounjaro pricing?

謝謝，特朗。 Mike，您想對 Mounjaro 定價發表任何評論嗎？

Yes. No, I'd be happy to do that. I think maybe at a macro level, I would say that our gross-to-net for Mounjaro in Q3, kind of normalized. Before then, we had a number of saving card changes that made our gross-to-net rate dynamic. Our last co-pay card change occurred late in Q2, so at the end of June, and so we -- Q3 was kind of a pure quarter where we didn't have any other co-pay card changes. And I would say that our Mounjaro rate normalized at that point.

是的。不，我很樂意這樣做。我認為也許在宏觀層面上，我會說我們第三季 Mounjaro 的總淨值比已經趨於正常化。在此之前，我們對儲蓄卡進行了多次更改，使我們的總淨利率變得動態。我們最後一次共同支付卡變更發生在第二季度末，即六月底，因此第三季度是一個純粹的季度，我們沒有任何其他共同支付卡變更。我想說的是，我們的蒙札羅率在那時已經正常化了。

Going forward, I think what you'll see is what you see normally out of -- for a product at this point in the life cycle, that as we pursue gaining access, there'll probably be some pricing pressure related to that. But we don't have any other co-pay card changes planned in the near future.

展望未來，我認為您將看到的是您通常會看到的情況——對於生命週期中此時的產品，當我們尋求獲得訪問權限時，可能會出現一些與之相關的定價壓力。但我們在不久的將來沒有計劃進行任何其他共同支付卡變更。

The next question is coming from Robyn Karnauskas from Truist Securities.

下一個問題來自 Truist Securities 的 Robyn Karnauskas。

This is Nicole on for Robyn. Just going back to obesity. How are you thinking through the impact on Mounjaro if IRA stays and Wegovy and Ozempic prices decline in the 2026, 2027 time frame?

這是妮可為羅賓代言的。只是回到肥胖。如果 IRA 繼續存在且 Wegovy 和 Ozempic 價格在 2026 年、2027 年期間下降，您如何看待對 Mounjaro 的影響？

Thanks, Nicole, for the question. I think it's -- if I heard you right, you're thinking about IRA impacts to maybe semaglutide and potential impacts to Mounjaro. Mike, do you want to comment on that quickly?

謝謝妮可的提問。我認為，如果我沒聽錯的話，您正在考慮 IRA 對索馬魯肽的影響以及對 Mounjaro 的潛在影響。麥克，你想快速對此發表評論嗎？

Yes. I'm happy to do that. Obviously, it's too early to really impact -- how IRA will have an impact and the impact will have another product within the class. I think what's important for tirzepatide is it is the first dual-acting incretin. And we do think it has a unique profile. And in head-to-head results in type 2 diabetes that did show superior, both A1c and [weight] to semaglutide. And so at the end of the day, I think the profile of the product will carry the day. And obviously, more to come on the RA as the first products go through the negotiation, we'll see with that. But we're confident in the profile of tirzepatide.

是的。我很高興這樣做。顯然，現在要真正產生影響還為時過早——IRA 將如何產生影響，以及該影響將對該類別中的另一個產品產生影響。我認為對替澤帕肽來說重要的是它是第一個雙重作用的腸促胰島素。我們確實認為它具有獨特的形象。在第 2 型糖尿病的頭對頭結果中，A1c 和 [體重] 確實優於索馬魯肽。因此，歸根究底，我認為產品的形象將會佔據主導地位。顯然，隨著第一批產品通過談判，RA 中還會有更多內容，我們拭目以待。但我們對替澤帕肽的概況充滿信心。

The first one is a follow-up from Seamus Fernandez from Guggenheim.

第一個是古根漢的謝默斯費爾南德斯 (Seamus Fernandez) 的後續作品。

Great. Thanks for the follow-up question. So just in terms of how you're thinking about the introduction of oral treatments and the importance of pushing for what would be hopefully a maintenance-type regimen. Is Lilly looking at oral therapies as more of a maintenance regimen opportunity? Or do you see a broader opportunity here, perhaps bringing in other mechanisms that perhaps could aid in pursuing, I guess, the ever-elusive metabolic set point?

偉大的。感謝您的後續問題。因此，就您如何考慮引入口服治療以及推動維持型治療方案的重要性而言。禮來公司是否將口服療法視為更多的維持方案機會？或者你在這裡看到了更廣泛的機會，也許引入了其他機制，也許可以幫助追求永遠難以捉摸的代謝設定點？

Dan, do you want to comment on that?

丹，你想對此發表評論嗎？

Yes. Thanks, Seamus. So maybe -- to Dave's previous answer, it's sort of an all of the above here. I think there's great opportunities on the oral as a stand-alone therapy for initiation of therapy. Also, yes, for maintenance therapy globally. And also, yes, for potential combinations. I point out the obvious fact that this is a GLP-1 monotherapy so we benchmark it against the best injectable, GLP-1 monotherapy. But I don't expect, as an oral, it will achieve the same levels of [X] we can see with dual agonism like tirzepatide. So the future certainly will hold combinations like that.

是的。謝謝，西莫。所以也許 - 對於戴夫之前的回答，這就是以上所有內容。我認為口服作為開始治療的獨立療法有很大的機會。另外，是的，全球維持治療。是的，還有潛在的組合。我指出一個明顯的事實，即這是一種 GLP-1 單一療法，因此我們將其與最佳注射 GLP-1 單一療法進行基準測試。但我不認為，作為口服藥物，它會達到與替澤帕肽等雙重激動作用相同的 [X] 水平。所以未來一定會出現這樣的組合。

And last question, Paul, from the queue.

最後一個問題，保羅，來自隊列。

The last question will be a follow-up from Tim Anderson from Wolfe Research.

最後一個問題將由沃爾夫研究公司的蒂姆·安德森提出。

What's the latest thinking on the topic of GIP agonism versus antagonism? So tirzepatide is the former Amgen's drug is the latter, I've never seen 2 drugs in any category that have a similar clinical effect, but opposing underlying activity of the biologic target. Amgen says GIP antagonism is the way to go, supported by their genetic analyses. Whereas Lilly think, have you looked similarly at genetic analyses to inform your view?

關於 GIP 激動與拮抗主題的最新想法是什麼？因此，替西帕肽是前者，安進的藥物是後者，我從未見過任何類別中的兩種藥物具有相似的臨床效果，但與生物標靶的潛在活性相反。 Amgen 表示 GIP 拮抗作用是可行的方法，並且得到了他們的基因分析的支持。莉莉認為，您是否也透過類似的基因分析來表達您的觀點？

Thank you, Tim, for the last question. Dan?

謝謝蒂姆的最後一個問題。擔？

Yes, I'll take that. Of course, we have now, I think, more data on GIP agonism than anyone in the world. And starting with tirzepatide, of course, which is a combo GLP-1, GIP agonist and head-to-head study against a pure GLP-1 agonist. And you can see some profoundly different effects here looking at, for example, efficacy relative to tolerability. It looks like the GIP is boosting efficacy while also reducing the side effects that limit tolerability. So that was our initial evidence in human trials that involved -- well, now tens of thousands of patients have been on tirzepatide in trials.

是的，我會接受的。當然，我認為我們現在擁有的有關 GIP 激動的數據比世界上任何人都多。當然，首先是替澤帕肽，它是 GLP-1、GIP 激動劑的組合，並且是針對純 GLP-1 激動劑的頭對頭研究。您可以在這裡看到一些截然不同的效果，例如相對於耐受性的療效。看起來 GIP 正在提高療效，同時也減少了限制耐受性的副作用。這是我們在人體試驗中的初步證據，現在有數萬名患者正在接受替澤帕肽治療。

And then we went out to sort of prove this point by creating a pure GIP1 agonist that just agonizes GIP to see what that could do alone. And again, we saw a very highly tolerated drug, consistent with what we understand about the mechanism of GLP-1 that probably could suppress actually nausea and vomiting, that led to weight loss. So I think human data trumps everything here, and we've got a ton of that. So we're pretty excited about GIP agonism. I can't really say what will happen with antagonism. But like you said, it's pretty unusual to have opposing mechanisms to both work in similar ways.

然後我們透過創建一種純 GIP1 激動劑來證明這一點，該激動劑只會讓 GIP 感到痛苦，看看它單獨能發揮什麼作用。我們再次看到了一種耐受性非常高的藥物，與我們對 GLP-1 機制的理解一致，它可能實際上可以抑制噁心和嘔吐，從而導致體重減輕。所以我認為人類數據勝過一切，我們已經有很多這樣的數據了。所以我們對 GIP 激動劑感到非常興奮。我真的不能說對抗會發生什麼事。但就像你說的，兩種機制以相似的方式工作的相反機制是很不尋常的。

Thanks, Dan for the last one. Dave?

謝謝丹，最後一篇。戴夫？

Okay. Thanks, Joe. We appreciate everyone's participation in today's earnings call and of course, your ongoing interest in Eli Lilly and Company. As I said, it's been a very productive year for Lilly so far, and we look forward to continuing this momentum through a busy end of year and fourth quarter.

好的。謝謝，喬。我們感謝大家參與今天的財報電話會議，當然也感謝你們對禮來公司的持續關注。正如我所說，到目前為止，對於禮來公司來說，這是非常富有成效的一年，我們期待在繁忙的年底和第四季度繼續保持這一勢頭。

So thanks for dialing in today. Please follow up with the IR team if you have questions we did not address on the call. And hope everyone has a great rest of the week and rest of the day today. Take care.

感謝您今天撥通電話。如果您有我們在電話會議中未解決的問題，請與 IR 團隊聯絡。並希望每個人本周和今天都過得愉快。小心。

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 December 7 at midnight. You may access the replay system at any time by dialing 800-332-6854 and entering the access code 544467. International dialers can call (973) 528-0005.

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 12 月 7 日午夜。您可以隨時撥打 800-332-6854 並輸入存取代碼 544467 存取重播系統。國際撥號者可以撥打 (973) 528-0005。

Thank you for your participation. You may now disconnect your lines.

感謝您的參與。現在您可以斷開線路。