禮來公司 (LLY) 2023 Q4 法說會逐字稿

Ladies and gentlemen, thank you for standing by, and welcome to the Lilly Q4 2023 Earnings Call. (Operator Instructions) I would now like to turn the conference over to your host, Joe Fletcher, Senior Vice President of Investor Relations. Please go ahead.

女士們、先生們，感謝大家的支持，歡迎參加禮來公司 2023 年第四季財報電話會議。 （操作員指示）我現在想將會議轉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 for joining us for Eli Lilly and Company's Q4 2023 Earnings and 2024 Guidance Call. I'm Joe Fletcher, Senior President of Investor Relations.

早安，謝謝你，Paul，感謝您參加禮來公司 (Eli Lilly and Company) 的 2023 年第四季收益和 2024 年指導電話會議。我是喬‧弗萊徹，投資人關係資深總裁。

And joining me on today's call are: Dave Ricks, Lilly's Chair and CEO; Anat Ashkenazi, Chief Financial Officer; Dr. Dan Skovronsky, Chief Scientific Officer and President of Lilly Immunology; Anne White, President of Lilly Neuroscience; Ilya Yuffa, President of Lilly International; Jake Van Naarden, President of Loxo at Lilly; and Patrik Jonsson, President of Lilly Diabetes and Obesity and Lilly U.S.A. We're also joined by Michaela Irons, Mike Springnether and Lauren Zierki of the Investor Relations team.

參加今天電話會議的有：禮來公司董事長兼執行長 Dave Ricks；阿納特‧阿什肯納齊 (Anat Ashkenazi)，財務長； Dan Skovronsky 博士，禮來免疫學首席科學官兼總裁； Anne White，禮來神經科學公司總裁；伊利亞‧尤法 (Ilya Yuffa)，禮來國際公司總裁； Jake Van Naarden，禮來公司 Loxo 總裁；禮來糖尿病和肥胖部總裁帕特里克·瓊森 (Patrik Jonsson) 以及禮來美國 (Lilly U.S.A.) 總裁。投資者關係團隊的 Michaela Irons、Mike Springnether 和 Lauren Zierki 也加入了我們的行列。

During this conference call, we anticipate making projections and forward-looking statements based on our current expectations. 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。

All right. Thanks, Joe. 2023 was a year of advancement across our company. We grew our top line, we progressed our pipeline, advanced our external innovation agenda through partnerships and collaborations. We continued to invest in quality, the reliability and the resilience of our company's manufacturing infrastructure and, most importantly, delivered new life-saving and life-changing medicines to more patients.

好的。謝謝，喬。 2023年是我們公司全面進步的一年。我們透過夥伴關係和協作增加了營收，推進了產品線，推動了外部創新議程。我們繼續投資於公司生產基礎設施的品質、可靠性和彈性，最重要的是，為更多患者提供了新的拯救生命和改變生命的藥物。

In 2023, revenue grew 20% for the full year and 28% for the most recent quarter as our newly launched portfolio continued to gain momentum. This past year, we announced positive Phase IIIs for donanemab, tirzepatide, mirikizumab and pirtobrutinib. We also announced a positive Phase II result for orforglipron as well as retatrutide and moved these two important molecules into Phase III.

2023 年，隨著我們新推出的產品組合繼續保持強勁勢頭，全年營收成長 20%，最近一個季度營收成長 28%。去年，我們宣布了 donanemab、tirzepatide、mirikizumab 和 pirtobrutinib 的 III 期臨床試驗取得積極進展。我們也宣布了 orforglipron 和瑞他魯肽的 II 期臨床試驗結果，並將這兩個重要分子轉移到 III 期臨床。

In terms of external innovation, in 2023, we continued to complement our pipeline through acquisitions and collaborations. These transactions included the acquisition of DICE Therapeutics, POINT Biopharma, Versanis Bio, Emergence Therapeutics, Mablink Bioscience, Immunitrack as well as Sigilon Therapeutics.

在外部創新方面，2023年，我們繼續透過收購和合作來補充我們的產品線。這些交易包括收購 DICE Therapeutics、POINT Biopharma、Versanis Bio、Emergence Therapeutics、Mablink Bioscience、Immunitrack 以及 Sigilon Therapeutics。

We announced several significant investments in manufacturing, including plans to expand capacity at the company's Research Triangle Park facility and the two manufacturing sites within the LEAP Innovation Park in Boone County, Indiana. Most recently, we announced plans to construct a new high-tech manufacturing site in Germany. This facility will further expand the company's global injectable product and device manufacturing network, including for our diabetes and obesity portfolio.

我們宣布了幾項重大的製造業投資，包括擴大公司三角研究園區設施和印第安納州布恩縣 LEAP 創新園區內兩個製造基地的產能的計畫。最近，我們宣布計劃在德國建造一個新的高科技製造基地。該工廠將進一步擴大該公司的全球注射產品和設備製造網絡，包括我們的糖尿病和肥胖產品組合。

Most importantly, this past year, we brought innovative new medicines to patients. In 2023, we received regulatory approvals for Zepbound, Jaypirca, Omvoh, Ebglyss in the U.S. -- in the EU rather and an expanded label for Verzenio and two new indications for Jardiance. This progress will serve as a foundation to drive top-tier revenue growth and margin expansion over time.

最重要的是，去年，我們為患者帶來了創新的新藥。 2023 年，我們在美國而非歐盟獲得了 Zepbound、Jaypirca、Omvoh、Ebglyss 的監管批准，以及 Verzenio 的擴展標籤和 Jardiance 的兩個新適應症。隨著時間的推移，這項進展將為推動頂級營收成長和利潤率擴張奠定基礎。

As you can see on Slide 4, we continue to make progress against our strategic deliverables in Q4. Revenue grew 28% with our new products growing by over $2 billion. Since our last earnings call, we achieved several key pipeline milestones. In addition to the Zepbound and Jaypirca CLL approvals, today, we announced top line results for the tirzepatide Phase II SYNERGY-NASH trial as well as the Verzenio Phase III CYCLONE 2 trial. Dan will talk more about this update -- in his update.

正如您在投影片 4 中所看到的，我們在第四季的策略交付成果上繼續取得進展。我們的新產品收入成長了 20 億美元以上，營收成長了 28%。自上次財報電話會議以來，我們實現了幾個關鍵的管道里程碑。除了 Zepbound 和 Jaypirca CLL 獲得批准外，今天，我們還宣布了 tirzepatide II 期 SYNERGY-NASH 試驗以及 Verzenio III 期 CYCLONE 2 試驗的主要結果。 Dan 將在他的更新中詳細討論此更新。

In terms of business development, in Q4, we completed the acquisitions of Mablink Bioscience and POINT Biopharma, the latter of which expands our capacity and capability into radioligand therapies. Lastly, we announced a 15% dividend increase for the sixth consecutive year and distributed over $1 billion in dividends in the fourth quarter.

在業務發展方面，第四季度，我們完成了對 Mablink Bioscience 和 POINT Biopharma 的收購，後者將我們的產能和能力擴展到放射配體治療領域。最後，我們宣布連續第六年將股息增加 15%，並在第四季度派發了超過 10 億美元的股息。

On Slide 5, you'll see a list of key events since our Q3 earnings call, including several important regulatory, clinical and other updates. Now I'll turn the call over to Anat to review our Q4 results.

在投影片 5 上，您將看到自第三季財報電話會議以來的關鍵事件列表，包括一些重要的監管、臨床和其他更新。現在我將把電話轉給 Anat，以審查我們第四季度的業績。

Thanks, Dave. Slide 6 summarizes financial performance in the fourth quarter of 2023. And I'll focus my comments on non-GAAP performance. We are pleased with the strong financial performance in the fourth quarter and for the full year. Our performance was highlighted by continued acceleration of revenue growth, driven by our new products and growth products.

謝謝，戴夫。第 6 張投影片總結了 2023 年第四季的財務業績。我將重點評論非 GAAP 業績。我們對第四季和全年強勁的財務業績感到滿意。在新產品和成長產品的推動下，營收持續加速成長凸顯了我們的業績。

Q4 revenue increased 28% compared to Q4 2022. Excluding divestiture, this represents a quarter-over-quarter acceleration revenue growth driven by Mounjaro, Verzenio, Jardiance and the recent launch of Zepbound. For the full year, revenue increased 20%, driven by robust volume growth of 16%. Gross margin as a percent of revenue increased to 82.3%. Gross margin in the quarter benefited from higher realized prices, partially offset by higher manufacturing expenses.

與 2022 年第四季相比，第四季營收成長了 28%。不包括資產剝離，這意味著在 Mounjaro、Verzenio、Jardiance 和最近推出的 Zepbound 的推動下，營收環比加速成長。全年銷量成長 16%，營收成長 20%。毛利率佔收入的百分比上升至 82.3%。本季的毛利率受益於較高的實際價格，但部分被較高的製造費用所抵消。

Marketing, selling and administrative expenses increased 17%, primarily driven by higher expenses associated with launches of new products and additional indications as well as higher incentive compensation costs. R&D expenses increased 28%, primarily driven by higher development expenses for late-stage assets and additional investments in early-stage research as well as higher incentive compensation costs.

行銷、銷售和管理費用增加了 17%，主要是由於與新產品和其他適應症的推出相關的費用增加以及激勵補償成本增加。研發費用增加 28%，主要是由於後期資產的開發費用增加、早期研究的額外投資以及激勵補償成本增加。

In Q4, we recognized acquired IPR&D charges of $623 million, which negatively impacted EPS by $0.62. In Q4 2022, acquired IPR&D charges totaled $240 million or $0.23 negative impact to EPS.

第四季度，我們確認收購的 IPR&D 費用為 6.23 億美元，這對 EPS 產生了 0.62 美元的負面影響。 2022 年第四季度，收購的智慧財產權與研發費用總計 2.4 億美元，對每股盈餘產生 0.23 美元的負面影響。

Operating income increased 29% in Q4, driven by higher revenue from new launches, partially offset by operating expense growth. Operating income as a percent of revenue was approximately 28% for the quarter and included a negative impact of approximately 7 percentage points attributable to acquired IPR&D charges.

由於新產品推出帶來的收入增加，第四季度營業收入成長了 29%，但部分被營業費用成長所抵銷。本季營業收入佔收入的百分比約為 28%，其中包括因收購的智慧財產權與開發費用而產生約 7 個百分點的負面影響。

Our Q4 effective tax rate was 13.1% compared to 7.3% in Q4 2022. The higher effective tax rate for Q4 2023 was primarily driven by a lower net discrete tax benefit compared to the same period in 2022 and the new Puerto Rico tax regime. At the bottom line, we delivered earnings per share of $2.49 in Q4, a 19% increase compared to Q4 2022, inclusive of the negative impact of $0.62 from acquired IPR&D charges compared to $0.23 in Q4 2022.

我們第四季的有效稅率為13.1%，而2022 年第四季為7.3%。2023 年第四季的有效稅率較高，主要是由於與2022 年同期相比淨離散稅收優惠較低以及新的波多黎各稅制。從底線來看，我們第四季的每股盈餘為2.49 美元，與2022 年第四季相比成長了19%，其中包括收購的IPR&D 費用帶來的0.62 美元的負面影響，而2022 年第四季度為0.23 美元。

On Slide 8, we quantify the effect of price, rate and volume on revenue growth. U.S. revenue increased 39% in Q4, driven by robust growth of Mounjaro, Verzenio and Zepbound. Net price in the U.S. increased 27% for the quarter, driven by Mounjaro access and savings cards dynamic as well as a one-time favorable change in estimates for rebates and discounts. Excluding Mounjaro, net price in the U.S. decreased by high single digits.

在投影片 8 中，我們量化了價格、費率和數量對收入成長的影響。在 Mounjaro、Verzenio 和 Zepbound 強勁成長的推動下，第四季美國營收成長了 39%。在 Mounjaro 准入卡和儲蓄卡動態以及回扣和折扣預估的一次性有利變化的推動下，本季度美國的淨價格增長了 27%。不包括Mounjaro，美國的淨價下降了高個位數。

Europe continued its trend of strong growth in Q4. Excluding $65 million in revenue associated with milestones received for the EU approval and launch of Ebglyss, revenue was up 11% in constant currency, driven primarily by volume growth of Verzenio, Jardiance and Taltz. For Japan, we are pleased to see robust growth in Q4 as revenue increased 15% in constant currency, driven primarily by volume growth of Verzenio and Mounjaro.

歐洲第四季持續保持強勁成長趨勢。不包括與歐盟批准和推出 Ebglyss 所獲得的里程碑相關的 6500 萬美元收入，按固定匯率計算，收入增長了 11%，這主要是由 Verzenio、Jardiance 和 Taltz 的銷量增長推動的。對於日本，我們很高興看到第四季度的強勁增長，按固定匯率計算，收入增長了 15%，這主要是由 Verzenio 和 Mounjaro 的銷售增長推動的。

Moving to China. Q4 revenue increased 7% in constant currency with volume growth of 10% partially offset by price declines. Volume growth in Q4 was primarily driven by Tyvyt. We are pleased to see China return to growth in 2023. Revenue in the rest of the world decreased 10% in constant currency. However, when you exclude the impact of the Q4 2022 sales of rights for Alimta in Korea and Taiwan, sales grew 9% in constant currency, driven primarily by volume growth of Mounjaro and Verzenio.

搬到中國。以固定匯率計算，第四季營收成長 7%，銷量成長 10%，部分被價格下跌所抵銷。第四季的銷售成長主要是由達伯舒推動的。我們很高興看到中國在 2023 年恢復成長。以固定匯率計算，世界其他地區的收入下降了 10%。然而，如果排除 2022 年第四季度 Alimta 在韓國和台灣的版權銷售的影響，按固定匯率計算，銷售額增長了 9%，這主要是受到 Mounjaro 和 Verzenio 銷量增長的推動。

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 15 percentage points of volume growth for the quarter.

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 15 個百分點。

Slide 10 provides additional perspective across our product categories. First, I would like to highlight Verzenio, which saw worldwide sales growth of 42% in Q4, driven by robust demand growth and, to a lesser extent, higher realized prices. The continued positive momentum is driven by early breast cancer indication with steady performance in the metastatic indication. Jardiance continued its strong 2023 performance with worldwide revenue growth of 30% for the quarter. In the U.S., Jardiance revenue increased 29%, driven by increased demand.

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，在強勁的需求成長以及較小程度上更高的實現價格的推動下，第四季全球銷售額成長了 42%。持續的正面動力是由早期乳癌適應症和轉移適應症的穩定表現所推動的。 Jardiance 持續維持 2023 年的強勁業績，該季度全球營收成長 30%。在美國，由於需求增加，Jardiance 收入增加了 29%。

In Q4, worldwide Trulicity revenue declined 14%. U.S. revenue decreased 18% driven by lower volume and lower realized prices. We experienced intermittent delays fulfilling orders of Trulicity. Starting in early December and going through January, all dose strengths of Trulicity were indicated as having limited availability on the FDA drug shortages site. We expect to experience intermittent delays fulfilling orders of certain doses in the coming months. In international markets, Trulicity volume continued 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.

在第四季度，Trulicity 全球營收下降了 14%。由於銷量下降和實現價格下降，美國收入下降了 18%。我們在履行 Trulicity 的訂單時遇到了間歇性的延誤。從 12 月初開始一直到 1 月份，FDA 藥物短缺網站上顯示 Trulicity 的所有劑量強度都有限。我們預計在未來幾個月內履行某些劑量的訂單將會出現間歇性延誤。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溝通，不要讓新患者開始使用 Trulicity。

Moving to Slide 11. Mounjaro continued its robust growth as more type 2 diabetes patients benefited from the medicine. Q4 revenue grew to over $2.2 billion globally, up from $1.4 billion in Q3 2023. In the U.S., Mounjaro revenue of $2.1 billion in Q4, up from $1.3 billion in Q3 2023, benefited from a one-time change in estimates for rebates and discounts. Adjusted for this one-time change, sequential net sales in the U.S. would have grown approximately 30% in Q4.

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，Mounjaro 繼續保持強勁增長。全球第四季營收成長至超過22 億美元，高於2023 年第三季的14 億美元。在美國，Mounjaro 第四季營收為21 億美元，高於2023 年第三季的13 億美元，這得益於回扣和折扣預估的一次性變化。根據這一一次性變化進行調整後，第四季美國的環比淨銷售額將成長約 30%。

Since our last call, we further expanded patient access to Mounjaro. As of February 1, access for patients with type 2 diabetes in the U.S. was 90% in aggregate across commercial and Part D, including 92% access for commercial patients. This expanded access puts Mounjaro near parity with established injectable incretins and gives more patients the opportunity to start therapy on Mounjaro for type 2 diabetes.

自上次通話以來，我們進一步擴大了患者接觸 Mounjaro 的範圍。截至 2 月 1 日，美國 2 型糖尿病患者的商業化和 D 部分的訪問率為 90%，其中商業患者的訪問率為 92%。這項擴大的使用範圍使 Mounjaro 幾乎與現有的注射用腸降血糖素相當，並讓更多患者有機會開始使用 Mounjaro 治療第 2 型糖尿病。

Since the $25 non-covered co-pay card program expired on June 30, we now consider all prescriptions paid. Compared to Q4 2022, the Mounjaro net price in Q4 2023 benefited from this change to the co-pay card program in the U.S. Recall that after a change to the non-covered co-pay program in late 2022, patients already started on the $25 co-pay card could remain in the program until June 30. Today, commercially insured patients without coverage utilize the current non-covered co-pay program and pay roughly half the list price for Mounjaro prescription.

由於 25 美元的非承保共付卡計劃已於 6 月 30 日到期，我們現在考慮所有已支付的處方藥。與2022 年第四季相比，2023 年第四季的Mounjaro 淨價受益於美國自付卡計畫的這項變更。回想一下，在2022 年底對非承保自付卡計畫進行變更後，病患已經開始使用25 美元共付卡可以保留在該計劃中直至 6 月 30 日。如今，沒有保險的商業保險患者可以使用當前未承保的共付計劃，並支付 Mounjaro 處方藥標價的大約一半。

Turning to Slide 12. In November, we received the FDA approval for Zepbound for adults with obesity or those who are overweight and have weight-related co-morbidities. We then announced on December 5 that Zepbound was available at U.S. pharmacies, and we started building commercial formulary access before the end of the year. We are pleased with the early access of approximately 1/3 of commercial lives covered as of February 1.

轉向幻燈片 12。11 月，我們獲得 FDA 批准 Zepbound 用於治療成人肥胖或超重且患有體重相關併發症的患者。隨後，我們在 12 月 5 日宣布 Zepbound 在美國藥局上市，並在年底前開始建立商業處方准入。我們很高興能夠搶先體驗截至 2 月 1 日涵蓋的大約 1/3 的商業生活。

Access in this market will be more gradual as individual employers need to opt in to coverage after the typical formulary contracting takes place. We are focused on building formulary access and employer opt-ins. But we expect that it will take some time before we reach broad open access in this market. Meanwhile, the commercial savings for our program is available at U.S. pharmacies for those who do not yet have coverage.

由於個體雇主需要在典型的處方合約簽訂後選擇加入保險，因此進入該市場將更加漸進。我們專注於建立處方准入和雇主選擇加入。但我們預計，在這個市場上實現廣泛的開放准入還需要一段時間。同時，對於那些尚未投保的人，我們的計劃的商業儲蓄可在美國藥房獲得。

In Medicare Part D, weight loss drugs are still prohibited from reimbursement. In Q4, we recognized $176 million in sales for Zepbound with approximately 3/4 of that coming from initial channel stocking. The initial prescription trends we have seen are encouraging.

在Medicare D部分中，減肥藥物仍然被禁止報銷。第四季度，我們確認 Zepbound 的銷售額為 1.76 億美元，其中約 3/4 來自初始通路庫存。我們看到的最初處方趨勢令人鼓舞。

On Slide 13, we provide an update on capital allocation. Looking forward to 2024 and beyond, we have confidence in our existing commercial portfolio, bolstered by the recent launches of Mounjaro, Jaypirca, Omvoh and Zepbound and the potential launches of the donanemab and lebrikizumab, all of which we expect to serve as drivers for continued growth through the balance of the decade.

在投影片 13 中，我們提供了資本配置的最新情況。展望 2024 年及以後，我們對現有的商業產品組合充滿信心，這得益於最近推出的 Mounjaro、Jaypirca、Omvoh 和 Zepbound 以及潛在推出的 donanemab 和 lebrikizumab，所有這些我們預計將成為持續的驅動力十年餘下時間的成長。

On Slide 14, you'll see a summary of our outlook that outline our capital deployment decisions in relation to achievement of our strategic deliverables. We will invest in our current portfolio and in the future innovation through R&D, business development and a comprehensive manufacturing expansion agenda designed to drive revenue growth and speed life-changing medicines to patients. We will continue to return capital to our shareholders through dividend increases in line with earnings growth over time and share repurchases with excess capital.

在投影片 14 上，您將看到我們的展望摘要，其中概述了我們與實現策略交付成果相關的資本部署決策。我們將透過研發、業務發展和全面的製造擴張議程投資於我們當前的產品組合和未來的創新，旨在推動收入成長並加快為患者提供改變生活的藥物。我們將繼續透過根據收益成長增加股利以及用多餘資本回購股票來向股東返還資本。

Moving to Slide 15. We highlight some of the dynamics that may impact our 2024 financial results. We expect continued robust revenue growth with revenue from our core business, which excludes revenue from divestiture, growing nearly 30% at the midpoint of our guidance range, driven by positive momentum from recently launched products.

轉到投影片 15。我們重點介紹了可能影響我們 2024 年財務表現的一些動態。我們預計，在最近推出的產品的積極勢頭的推動下，我們的核心業務收入（不包括剝離收入）將持續強勁增長，在我們指導範圍的中點增長近 30%。

In incretins, anticipated growth will be led by Mounjaro and Zepbound. In 2023, we made tremendous strides in expanding access for Mounjaro. And we entered 2024 with 90% of commercial and Part D lives covered. Zepbound coverage is off to a good start in its early December launch. And we expect both tirzepatide brands to contribute substantially to Lilly's revenue growth in 2024.

在腸促胰島素方面，預計成長將由 Mounjaro 和 Zepbound 引領。 2023 年，我們在擴大 Mounjaro 的訪問範圍方面取得了巨大進展。進入 2024 年，我們已經涵蓋了 90% 的商業和 D 部分生活。 Zepbound 報導在 12 月初的發布中取得了良好的開端。我們預計這兩個替澤帕肽品牌都將為禮來公司 2024 年的營收成長做出重大貢獻。

While we expect Mounjaro and Zepbound to be drivers of revenue growth, this will be partially offset by an expected continuation of the softer Trulicity sales trends that we saw in the second half of 2023. Recent revenue declines for Trulicity in the U.S. has been driven by supply tightness. Volume has also been impacted by our actions outside the U.S.

雖然我們預計 Mounjaro 和 Zepbound 將成為營收成長的驅動力，但這將被我們在 2023 年下半年看到的 Trulicity 銷售趨勢的持續疲軟所部分抵消。Trulicity 最近在美國的收入下降是由於供應緊張。我們在美國以外的行動也影響了銷售量。

As for supply outlook for incretin, our manufacturer organization continues to execute well on the most ambitious expansion agenda in our company's long history. Given strong demand and time required to bring capacity fully online, we continue to expect demand to outpace supply in 2024. In late 2022, we shared our expectation that by year-end 2023, our capacity for incretin auto-injector pens would double. This goal was achieved through significant efforts from our manufacturing colleagues and partners around the globe.

至於腸促胰素的供應前景，我們的製造商組織繼續在我們公司悠久的歷史中最雄心勃勃的擴張議程上執行良好。鑑於需求強勁且產能完全上線所需的時間，我們仍預計 2024 年需求將超過供應。2022 年末，我們預計到 2023 年底，我們的腸促胰島素自動注射筆產能將增加一倍。這一目標是透過我們全球製造同事和合作夥伴的巨大努力實現的。

In 2024, our capacity expansion efforts will continue with equal urgency and will be accomplished not just through increased auto-injector capacity but also through alternative presentation like our multi-use KwikPen, which received regulatory approval in the U.K. in late January. We expect our perennial manufacturing site in Concord, North Carolina will initiate production as early as the end of 2024 with product available to ship in 2025. And we are pursuing a host of projects, internal and external, large and small, to further expand capacity.

到 2024 年，我們的產能擴張工作將同樣緊迫，不僅透過增加自動注射器產能來完成，還透過我們的多用途 KwikPen 等替代方案來完成，該產品於 1 月下旬在英國獲得了監管部門的批准。我們預計位於北卡羅來納州康科德的常年生產基地最早將於 2024 年底開始生產，產品將於 2025 年發貨。我們正在進行一系列內部和外部、大大小小的項目，以進一步擴大產能。

Now I'll provide a bit more context on the timing and pace of our incretin supply plans in 2024. While we're continuing to expand supply every quarter, we expect the most significant production increases to come in the second half of the year. We expect our production of sellable doses in the second half of 2024 will be at least 1.5x the production in the second half of 2023.

現在，我將提供有關 2024 年腸促胰素供應計劃的時間和節奏的更多背景資訊。雖然我們每個季度都會繼續擴大供應，但我們預計最顯著的產量增長將在今年下半年出現。我們預計 2024 年下半年的可銷售劑量產量將至少是 2023 年下半年產量的 1.5 倍。

Note that while last year, our commentary focused on capacity of auto-injectors devices compared to 2022, we're now referring sellable doses produced, which is more relevant to patients and investors. Beyond incretin, we look forward to progressing our launch trajectories for two other Lilly medicine approved and launched in 2023, Jaypirca and Omvoh.

請注意，雖然去年我們的評論重點是與 2022 年相比自動注射器設備的產能，但我們現在指的是生產的可銷售劑量，這與患者和投資者更相關。除了腸促胰素之外，我們期待著推進禮來公司於 2023 年批准和推出的另外兩種藥物 Jaypirca 和 Omvoh 的上市軌跡。

Jaypirca was initially approved by the FDA in January 2023 for adult patients with relapsed or refractory mantle cell lymphoma under the Accelerated Approval program received FDA approval also under the Accelerated Approval program in December 2023 for adult patients with CLL or SLL that have received at least two prior lines of therapy. We look forward to the ongoing opportunity to help patients with this medicine as our best Phase III program continues.

Jaypirca 最初於2023 年1 月獲得FDA 批准，用於治療復發或難治性套細胞淋巴瘤成人患者，並於2023 年12 月根據加速批准計劃獲得FDA 批准，用於治療至少接受過兩次治療的CLL 或SLL 成人患者。先前的治療方案。隨著我們最好的 III 期計畫的繼續，我們期待著持續的機會來幫助患者使用這種藥物。

Omvoh was approved in October 2023 in the U.S. and earlier that year in Japan, Europe and other markets and represents a compelling new options for patients struggling with moderate to severe ulcerative colitis. And in 2024, we look forward to potential U.S. launches of two more medicines, donanemab and lebrikizumab.

Omvoh 於2023 年10 月在美國獲得批准，並於當年早些時候在日本、歐洲和其他市場獲得批准，對於患有中度至重度潰瘍性結腸炎的患者來說，這是一個引人注目的新選擇。到 2024 年，我們期待美國可能推出另外兩款藥物：donanemab 和 lebrikizumab。

We continue to expect FDA regulatory actions on donanemab in Q4 2024 and remain confident in the substantial potential for donanemab to benefit patients with Alzheimer's disease. With the current state of diagnostic and treatment readiness, initial uptake will be somewhat limited. And we expect donanemab to contribute only modestly to growth in 2024 once approved.

我們仍預期 FDA 將於 2024 年第四季對多南單抗採取監管行動，並對多南單抗造福阿茲海默症患者的巨大潛力仍充滿信心。根據目前的診斷和治療準備情況，最初的吸收將受到一定程度的限制。我們預計，一旦獲得批准，donanemab 對 2024 年成長的貢獻微乎其微。

Lebrikizumab, which last year was approved and launched in Europe under the brand name Ebglyss by our partner, Almirall, received regulatory approval in Japan in January. As for the U.S., we look forward to the potential proof of lebrikizumab by the end of the year.

Lebrikizumab 去年由我們的合作夥伴 Almirall 在歐洲批准並以 Ebglyss 品牌上市，並於 1 月在日本獲得監管部門批准。至於美國，我們期待年底前獲得 lebrikizumab 的潛在證據。

We believe the efficacy, safety and dosing of lebrikizumab can make it a compelling option for patients and prescribers in a large and growing market for the treatment of moderate to severe atopic dermatitis. Given the expected timing of FDA regulatory action, we expect lebrikizumab to contribute only modestly to revenue growth in 2024.

我們相信，lebrikizumab 的功效、安全性和劑量可以使其成為龐大且不斷增長的中度至重度異位性皮膚炎治療市場中患者和處方者的一個令人信服的選擇。考慮到 FDA 監管行動的預期時間，我們預期 lebrikizumab 對 2024 年營收成長的貢獻有限。

Beyond our recently launched portfolio of medicine, we expect continued growth from Verzenio driven by the early breast cancer indication, where the magnitude and maturity of our clinical data reinforces it as a standard of care treatment in node-positive, high-risk early breast cancer. Jardiance has been another outstanding contributor to growth. And we expect revenue growth to continue in 2024 though at a slower pace as strong script growth may be dampened by pricing dynamics in the U.S.

除了我們最近推出的藥物組合之外，我們預計早期乳癌適應症將推動 Verzenio 的持續成長，我們臨床數據的規模和成熟度強化了它作為淋巴結陽性、高風險早期乳癌的護理治療標準。 Jardiance 是另一個對成長有傑出貢獻的人。我們預計 2024 年營收將繼續成長，但成長速度將放緩，因為強勁的劇本成長可能會受到美國定價動態的抑制。

Outside the U.S., we expect an acceleration of growth in every major geography led not only by the anticipated launches of tirzepatide but also continued strong growth of Verzenio, Jardiance and Taltz. Lastly, we seek to create long-term value beyond this decade. We will continue to invest across our value chain in our recent and upcoming potential launches, in our pipeline and in our manufacturing footprint.

在美國以外，我們預計每個主要地區的成長都會加速，這不僅是由於替澤帕肽的預期上市，而且是 Verzenio、Jardiance 和 Taltz 的持續強勁成長。最後，我們尋求在這十年之後創造長期價值。我們將繼續在我們的價值鏈中投資於我們最近和即將推出的潛在產品、我們的管道和我們的製造足跡。

Slide 16 summarizes our initial 2024 financial guidance. Starting at the top line, revenue is expected to be between $40.4 billion and $41.6 billion. Using the midpoint of the 2024 range, this represents roughly 20% growth or 29% growth for our core business, which excludes the impact of divestitures that took place in 2023.

投影片 16 總結了我們最初的 2024 年財務指引。從營收來看，營收預計在 404 億美元至 416 億美元之間。使用 2024 年範圍的中點，這意味著我們的核心業務成長約 20% 或 29%，其中不包括 2023 年剝離的影響。

In terms of phasing of our revenue growth throughout 2024, while we don't provide quarterly guidance, we expect revenue growth to accelerate in the second half of the year, consistent with the increased availability of incretin doses. In terms of pricing for our core business which excludes divestitures, we expect a high single-digit percent price decline in 2024. The lingering base period impact of the Mounjaro non-covered co-pay card dynamics will dampen these price declines in the first half of 2024 with more significant price declines expected in the second half of the year.

就 2024 年我們的營收成長分階段而言，雖然我們不提供季度指導，但我們預計收入成長將在今年下半年加速，這與腸促胰島素劑量的供應增加一致。就我們的核心業務（不包括資產剝離）的定價而言，我們預計 2024 年價格將出現個位數百分比的高跌幅。Mounjaro 非承保共付卡動態的持續基期影響將抑制上半年的價格跌幅2024年下半年，預計價格將出現更大幅度的下跌。

During this year, we are taking a streamlined approach to our guidance line items related to expenses. Rather than provide three separate guidance line items for gross margin, research and development costs and marketing and selling and administrative costs, we are presenting a single new ratio representing our margin after planned costs calculated by subtracting R&D costs and marketing, selling and administrative costs from gross margin and dividing that figure by revenue. We express this ratio as a percentage. And for 2024, we expect it to be in the range of 31% to 33% on a non-GAAP basis.

今年，我們對與費用相關的指導項目採取了簡化的方法。我們沒有為毛利率、研發成本以及行銷、銷售和管理成本提供三個單獨的指導項目，而是提出一個新的比率，代表我們在計劃成本後的利潤率，該比率是透過從計劃成本中減去研發成本以及行銷、銷售和管理成本來計算的。毛利率並將該數字除以收入。我們將該比率表示為百分比。到 2024 年，我們預計以非 GAAP 計算該比例將在 31% 至 33% 之間。

While we are not providing a specific guidance number for gross margin as a percent of sales, our expectations remain consistent that we will maintain gross margin of approximately 80% on a non-GAAP basis as productivity gains and volumes are offset by pricing pressures and the cost of new manufacturing facilities.

雖然我們沒有提供毛利率佔銷售額百分比的具體指導數字，但我們的預期仍然一致，即我們將在非 GAAP 基礎上保持約 80% 的毛利率，因為生產率的提高和銷量被定價壓力和新製造設施的成本。

As for our expense growth across key categories, we expect marketing and administrative expenses to again grow in 2024 though at a slower pace than revenues with growth driven by marketing investments in our recently launched and upcoming launch products.

至於我們在關鍵類別的費用成長，我們預計行銷和管理費用將在 2024 年再次成長，儘管成長速度低於收入，成長是由我們最近推出和即將推出的產品的行銷投資推動的。

We also expect R&D expenses in 2024 to increase, driven by growing investments across all phases of our pipeline as we invest for the future with the majority of dollar growth driven by ongoing and new late-phase opportunities. We expect R&D expense to increase at a higher rate than marketing, selling and administrative expenses. Other income and expense is expected to be between $400 million and $500 million of expense, primarily driven by higher interest expense.

我們也預計 2024 年的研發費用將會增加，這是由於我們對未來進行投資，而大部分美元成長是由持續的和新的後期機會推動的，這將推動我們管道各個階段的投資不斷增長。我們預期研發費用的成長速度將高於行銷、銷售和管理費用。其他收入和支出預計將在 4 億至 5 億美元之間，主要是由於利息支出增加。

Turning to taxes. We expect our 2024 non-GAAP effective tax rate to be approximately 14%. Note that this rate does not assume the deferral or repeal of the provision of the 2017 Tax Act requiring capitalization and amortization of research and development expenses for tax purposes. Should such a change take effect, our effective tax rate for 2024 would be moderately higher.

轉向稅收。我們預計 2024 年非 GAAP 有效稅率約為 14%。請注意，該比率並未假定推遲或廢除 2017 年稅法中要求出於稅收目的對研發費用進行資本化和攤銷的條款。如果這樣的變化生效，我們 2024 年的有效稅率將適度提高。

Earnings per share is expected to be in the range of $12.20 to $12.70 on a non-GAAP basis. Consistent with our prior practice, we are not including any potential or pending acquired IPR&D and development milestone charges in our 2024 guidance. And we will provide updates each quarter on the impact of IPR&D on earnings per share as acquired IPR&D and development milestone charges are incurred. For guidance modeling purposes, we're currently estimating diluted weighted average share outstanding for 2024 to be approximately 903 million.

以非公認會計準則計算，每股收益預計在 12.20 美元至 12.70 美元之間。與我們先前的做法一致，我們的 2024 年指南中不包括任何潛在或待收購的智慧財產權、研發和開發里程碑費用。我們將每個季度提供有關知識產權與開發對每股收益的影響的最新信息，因為收購的知識產權與開發和開發里程碑費用已產生。出於指導建模的目的，我們目前估計 2024 年稀釋後加權平均流通股約為 9.03 億股。

We enter 2024 with strong momentum and a remarkable opportunity to help millions more patients with our medicines. For our investors, 2024 should be another exciting year, driven by expected revenue growth in our core business near and approaching 30% and continued investments to drive future growth. Our outlook for top-tier revenue growth and operating margin expansion remains on track.

我們以強勁的勢頭和絕佳的機會進入 2024 年，利用我們的藥物幫助數百萬患者。對於我們的投資者來說，2024 年應該是另一個令人興奮的一年，這主要得益於我們核心業務的預期收入成長接近或接近 30%，以及持續投資以推動未來成長。我們對頂級收入成長和營業利潤率擴張的展望仍然正常。

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

現在我將把電話轉給 Dan，以強調我們在研發方面的持續進展。

Thanks, Anat. I'll start with our progress against diabetes, obesity and complications thereof. Today, we announced positive results from SYNERGY-NASH, the Phase II study of tirzepatide in adults with biopsy-proven metabolic dysfunction-associated steatohepatitis, also known as MASH.

謝謝，阿納特。我將從我們在對抗糖尿病、肥胖症及其併發症方面取得的進展開始。今天，我們宣布了 SYNERGY-NASH 的積極結果，這是替澤帕肽治療經活檢證實患有代謝功能障礙相關脂肪性肝炎（也稱為 MASH）的成人患者的 II 期研究。

As shown on Slide 17, the study met its primary endpoint with up to 74% of participants achieving an absence of MASH with no worsening of fibrosis at 52 weeks compared to less than 13% of participants reaching this endpoint on placebo. We are equally encouraged by results seen in the secondary endpoint, evaluating improvement in fibrosis.

如幻燈片17 所示，該研究達到了主要終點，高達74% 的參與者在52 週時實現了MASH 消失且纖維化沒有惡化，而安慰劑組中只有不到13% 的參與者達到了這一終點。我們同樣對次要終點（評估纖維化改善）的結果感到鼓舞。

While the study was not designed to be statistically powered to evaluate improvement in fibrosis, the study results showed a clinically meaningful treatment effect across all doses on the proportion of participants achieving a decrease of at least one fibrosis stage with no worsening of MASH to placebo. The adverse events were consistent with those observed in other clinical trials studying tirzepatide in people living with obesity or type 2 diabetes. The full SYNERGY-NASH results will be presented at a medical congress later this year.

雖然研究的設計目的不是為了在統計上評估纖維化的改善，但研究結果顯示，與安慰劑相比，所有劑量的參與者中實現至少一個纖維化階段減少且MASH 沒有惡化的比例都具有臨床意義的治療效果。這些不良事件與其他研究替西帕肽治療肥胖或第 2 型糖尿病患者的臨床試驗中觀察到的情況一致。完整的 SYNERGY-NASH 結果將在今年稍後的醫學大會上公佈。

As you know, late last year, we received FDA approval on Zepbound, which marks Lilly's first approved treatment for obesity. This is a landmark occasion for patients and for the field as Zepbound is the first and only approved treatment activating two incretin hormone receptors, GIP and GLP-1, to tackle an underlying cause of excess weight.

如您所知，去年年底，我們的 Zepbound 獲得 FDA 批准，這標誌著禮來公司第一個獲得批准的肥胖治療藥物。對於患者和該領域來說，這都是一個具有里程碑意義的時刻，因為Zepbound 是第一個也是唯一一個被批准激活兩種腸促胰島素受體（GIP 和GLP-1）的治療方法，以解決體重過重的根本原因。

Also, in early-stage development, we have now advanced our glucose-sensing insulin receptor agonist for the treatment of diabetes into Phase I and our long-acting atrial natriuretic peptide for treatment of heart failure into Phase I.

此外，在早期開發階段，我們目前已將用於治療糖尿病的葡萄糖敏感胰島素受體激動劑推進到第一階段，並將用於治療心臟衰竭的長效心房鈉尿肽推進到第一階段。

We've advanced mazdutide into Phase II for obesity as we've begun to dose patients in that study. We are pleased that early this year, our partner, Innovent, reported positive results in the Phase III GLORY-1 study of mazdutide in Chinese adults with obesity. Innovent holds the development and commercialization rights for mazdutide in China and Lilly retains the rights to the rest of the world.

我們已將 mazdutide 推進到治療肥胖症的 II 期臨床研究中，並開始對該研究中的患者進行給藥。我們很高興今年年初，我們的合作夥伴信達生物在中國成人肥胖症患者中報告了馬茲度肽 III 期 GLORY-1 研究的積極結果。信達生物擁有馬茲度勝肽在中國的開發和商業化權利，禮來公司保留在世界其他地區的權利。

Moving to oncology. Today, we shared that in the Phase III CYCLONE 2 trial, Verzenio added to abiraterone did not meet the primary endpoint of improved radiographic progression-free survival in men with metastatic castration-resistant prostate cancer. For the study, we employed an adaptive Phase II/III design.

轉向腫瘤學。今天，我們分享了在 III 期 CYCLONE 2 試驗中，添加阿比特龍的 Verzenio 並未達到改善轉移性去勢抵抗性前列腺癌男性放射學無進展生存期的主要終點。在這項研究中，我們採用了適應性 II/III 期設計。

And while the Phase II stage met the prespecified threshold for the independent data monitoring committee to recommend initiation of Phase III, the signal was not confirmed in the Phase III portion in a larger sample size. The overall safety and tolerability profile was consistent with the known profiles of the medicines. We anticipate sharing full results from the CYCLONE 2 study at a future medical meeting.

雖然第二階段階段達到了獨立數據監測委員會建議啟動第三階段的預先設定的閾值，但在較大樣本量的第三階段部分中，該訊號並未得到確認。整體安全性和耐受性概況與藥物的已知概況一致。我們預計在未來的醫學會議上分享 CYCLONE 2 研究的完整結果。

Since our last earnings call, Jaypirca received approval under the FDA's Accelerated Approval program for the treatment of adult patients with CLL or SLL who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor. We also reported that the Phase III confirmatory trial intended to convert this approval to traditional approval, known as BRUIN CLL-321, met its primary endpoint. And we plan to present these data at an upcoming medical meeting.

自從我們上次財報電話會議以來，Jaypirca 獲得了 FDA 加速審批計畫的批准，用於治療已接受過至少兩種既往療法（包括 BTK 抑制劑和 BCL-2 抑制劑）的 CLL 或 SLL 成年患者。我們還報告說，旨在將該批准轉換為傳統批准的 III 期驗證性試驗（稱為 BRUIN CLL-321）達到了其主要終點。我們計劃在即將舉行的醫學會議上展示這些數據。

With the CLL and SLL approvals, Jaypirca is now the first and only FDA-approved non-covalent BTK inhibitor that can extend the benefit of targeting the BTK pathway in CLL and SLL patients previously treated with a covalent BTK inhibitor and a BCL-2 inhibitor. This was the second approval for Jaypirca in 2023 with the first in patients with MCL. We believe these two indications only represent the beginning of the eventual impact Jaypirca can have for patients. And we look forward to seeing the data from the rest of the Phase III program across CLL, SLL and MCL.

隨著CLL 和SLL 的批准，Jaypirca 現在是第一個也是唯一一個FDA 批准的非共價BTK 抑制劑，它可以在先前接受共價BTK 抑制劑和BCL-2 抑制劑治療的CLL 和SLL 患者中擴大靶向BTK 路徑的益處。這是 Jaypirca 於 2023 年第二次獲得批准，第一次是在 MCL 患者中獲得批准。我們相信這兩個跡象僅代表 Jaypirca 對患者最終影響的開始。我們期待看到 CLL、SLL 和 MCL 的 III 期專案其餘部分的數據。

In Q4, we completed the acquisition of POINT Biopharma, which begins Lilly's entry into radioligand therapy, a promising technology with potential to deliver meaningful advances against a range of cancers. We welcome our new POINT colleagues to Lilly. And we look forward to building on their work to grow this capability at Lilly.

第四季度，我們完成了對 POINT Biopharma 的收購，這標誌著禮來公司開始涉足放射配體治療領域，這是一項很有前途的技術，有潛力為一系列癌症帶來有意義的進展。我們歡迎新的 POINT 同事加入禮來公司。我們期待以他們的工作為基礎，增強禮來公司的這種能力。

2024 is also poised to be a particularly productive year for new clinical starts in oncology as we begin to see the results of the new oncology R&D strategy that we implemented about 4 years ago after the Loxo acquisition. Through a combination of internal discovery efforts and business development, we expect to put at least five new molecules into the clinic this year: a wild-type selective KRAS G12D inhibitor; a pan-KRAS inhibitor; two antibody-drug conjugates with topoisomerase payloads, one against ACTN4 and one against folate receptor alpha; and an actinium PSMA radioligand therapy.

2024 年也將成為腫瘤學新臨床啟動特別有成效的一年，因為我們開始看到大約 4 年前收購 Loxo 後實施的新腫瘤學研發策略的結果。透過內部發現工作和業務發展的結合，我們預計今年將至少五種新分子投入臨床：一種野生型選擇性 KRAS G12D 抑制劑；泛 KRAS 抑制劑；兩種具有拓樸異構酶有效負載的抗體-藥物綴合物，一種針對 ACTN4，一種針對葉酸受體 α；和錒 PSMA 放射性配體療法。

I'll speak in a moment about our clinical KRAS G12C program. But you can see that we're putting real effort into developing a suite of RAS-directed therapeutics. And we're excited to see those discovery efforts result in three potential medicines so far. Of course, we'll have to see which of these deliver on our target clinical profiles. But we're optimistic about this early phase portfolio, and we've certainly diversified the modalities in our pipeline.

稍後我將談論我們的臨床 KRAS G12C 計劃。但您可以看到，我們正在真正努力開發一套 RAS 導向的療法。我們很高興看到迄今為止這些發現工作產生了三種潛在的藥物。當然，我們必須看看其中哪些能夠滿足我們的目標臨床特徵。但我們對這個早期階段的投資組合感到樂觀，而且我們當然已經使我們的管道模式多樣化。

In addition, we're excited that olomorasib, our KRAS G12C inhibitor, has progressed into Phase II as we're finalizing dose selection under Project Optimus for the Phase III program, which we plan to start later this year. You can now see the full design of that study on clinicaltrials.gov.

此外，我們很高興我們的 KRAS G12C 抑制劑 olomorasib 已進入 II 期，因為我們正在 Optimus 專案下完成 III 期專案的劑量選擇，我們計劃在今年稍後啟動該專案。現在您可以在 ClinicalTrials.gov 上查看該研究的完整設計。

By way of reminder, we started this program years huge behind our competitors. And through focused effort behind what looks like a great molecule to us, we've made up the vast majority of that time. We believe we're now neck-and-neck with our closest competitors with a medicine that we hope to show combines better with PD-1. Lastly, in oncology, we terminated development of our RET inhibitor 2 as it did not meet our threshold to move forward with internal development.

提醒一下，我們啟動這個專案的時間遠遠落後於我們的競爭對手。透過對我們看來偉大的分子的集中努力，我們已經彌補了絕大多數時間。我們相信，我們現在與最接近的競爭對手並駕齊驅，我們希望展示一種藥物與 PD-1 更好的結合。最後，在腫瘤學方面，我們終止了 RET 抑制劑 2 的開發，因為它沒有達到我們推進內部開發的門檻。

In immunology, we moved two new assets into Phase I and we advanced our Kv1.3 antagonist for psoriasis into Phase II. Lebrikizumab was approved in the EU for atopic dermatitis under the brand name Ebglyss, which is marketed by our partner, Almirall, there. In January this year, we were pleased to have Ebglyss approved in Japan.

在免疫學方面，我們將兩種新資產轉移到 I 期，並將治療牛皮癬的 Kv1.3 拮抗劑推進到 II 期。 Lebrikizumab 在歐盟被批准用於治療異位性皮膚炎，商品名為 Ebglyss，由我們的合作夥伴 Almirall 在那裡銷售。今年 1 月，我們很高興 Ebglyss 在日本獲得批准。

In neuroscience, in January, our wholly owned subsidiary, Akouos, announced positive clinical results for the Phase I/II AK-OTOF-101 study, which demonstrated hearing restoration within 30 days of a single administration in the first participant, an individual with more than a decade of profound hearing loss. The surgical administration and the investigational therapy were well tolerated and no serious adverse events were reported.

在神經科學領域，一月份，我們的全資子公司Akouos 宣布了I/II 期AK-OTOF-101 研究的積極臨床結果，該研究表明第一位參與者（患有更多疾病的個體）在單次給藥後30 天內恢復了聽力。超過十年的嚴重聽力損失。手術治療和研究性治療的耐受性良好，沒有嚴重不良事件的報告。

These results highlight our commitment to help solve some of humanity's most challenging health care problems and make life better for individual patients. We now show OTOF gene therapy in Phase II on our pipeline chart as we've begun enrolling younger patients in the Phase II portion of the study.

這些結果凸顯了我們致力於幫助解決人類最具挑戰性的一些醫療保健問題並改善個別患者的生活的承諾。現在，我們在管道圖上展示了 II 期的 OTOF 基因治療，因為我們已經開始在該研究的 II 期部分招募年輕患者。

On Slide 18, we highlight our select pipeline assets with updates since the last earnings call and Slide 19 summarizes our key events for 2023. I note the key updates on each of these slides in my therapeutic area of comments.

在投影片18 上，我們重點介紹了我們精選的管道資產以及自上次財報電話會議以來的更新，幻燈片19 總結了我們2023 年的關鍵事件。我在我的治療評論領域中註意到了每張投影片的關鍵更新。

Turning to Slide 20. We'd like to highlight potential key events for 2024. As you can see, this year will be another important year as we look to progress our late-stage pipeline. In 2023, we initiated Phase III development projects for our next generation of incretins, which are our oral agent, orforglipron, and our novel weekly injectable triagonist, retatrutide. These programs are progressing and enrolling well. We look forward to seeing the first set of Phase III results on orforglipron next year.

轉向幻燈片 20。我們想強調 2024 年潛在的關鍵事件。正如您所看到的，今年將是另一個重要的一年，因為我們希望推進我們的後期管道。 2023 年，我們啟動了下一代腸降血糖素的 III 期開發項目，這些項目是我們的口服製劑 orforglipron 和我們的新型每週注射三方藥物瑞他魯肽。這些項目進展順利，招生情況良好。我們期待明年看到 orforglipron 的第一組 III 期結果。

This year, we're planning to initiate a Phase III program in type 2 diabetes for retatrutide, complementing the ongoing trials in obesity and related complications. Also this year, we are planning to initiate a Phase III program for lepodisiran, our LPA-lowering siRNA therapy in cardiovascular disease.

今年，我們計劃啟動瑞他魯肽治療第 2 型糖尿病的 III 期項目，以補充正在進行的肥胖及相關併發症試驗。今年，我們還計劃啟動 lepodisiran 的 III 期項目，這是我們針對心血管疾病的降低 LPA 的 siRNA 療法。

On tirzepatide, we're looking forward to a number of additional key data readouts this year. Beyond SYNERGY-NASH, we expect to see results from the Phase III obstructive sleep apnea and Phase III heart failure studies this year. We note increased investor interest in the timing of SURPASS-CVOT. And we can reiterate that we expect the data in 2025, notwithstanding the clinicaltrials.gov listing, which will be updated soon to reflect our current assumptions based on event rate.

關於替澤帕肽，我們期待今年能獲得更多關鍵數據。除了 SYNERGY-NASH 之外，我們預計今年將看到第三期阻塞性睡眠呼吸中止症和第三期心臟衰竭研究的結果。我們注意到投資者對 SURPASS-CVOT 時機的興趣增加。我們可以重申，我們預計 2025 年會出現數據，儘管我們已經列出了 ClinicalTrials.gov 的列表，很快就會更新，以反映我們當前基於事件發生率的假設。

By the end of 2024, we expect to have results of SURMOUNT-5, which is our head-to-head study of tirzepatide compared to high-dose semaglutide in participants with obesity. We also expect the full Phase III program readout on our weekly basal insulin, insulin efsitora alfa, later this year.

到 2024 年底，我們預計將獲得 SURMOUNT-5 的結果，這是我們在肥胖參與者中對替澤帕肽與高劑量索馬魯肽進行比較的頭對頭研究。我們也預計今年稍後我們的每週基礎胰島素、胰島素 efsitora alfa 的完整 III 期計劃將公佈。

Moving to neuroscience. We're looking forward to FDA action and the potential launch of donanemab in Q1 of this year. And we are progressing with regulatory reviews around the world. We've now launched a P-tau217 blood-based diagnostic test. And we will continue to scale this throughout 2024. We'll also continue to partner with others in the field to ensure physicians have multiple tools to aid in timely and accurate diagnosis of Alzheimer's disease.

轉向神經科學。我們期待 FDA 採取行動以及可能在今年第一季推出 donanemab。我們正在世界各地推動監管審查。我們現在推出了基於 P-tau217 血液的診斷測試。我們將在 2024 年繼續擴大這一規模。我們也將繼續與該領域的其他公司合作，確保醫生擁有多種工具來幫助及時、準確地診斷阿茲海默症。

In immunology, following the mirikizumab positive Phase III data in Crohn's disease, we plan to submit to the FDA for this indication this year. Additionally, following the U.S. FDA complete response letter on lebrikizumab, we expect regulatory action by the end of the year in the U.S.

在免疫學方面，繼mirikizumab治療克隆氏症的III期臨床數據呈陽性後，我們計劃今年向FDA提交該適應症的申請。此外，在美國 FDA 完成對 lebrikizumab 的答覆函之後，我們預計美國將於今年底採取監管行動。

Finally, in oncology, as I mentioned before, we look forward to moving our KRAS G12C inhibitor, olomorasib, into Phase III later this year following Phase II dose selection. Lastly, we're looking forward to seeing the results of our imlunestrant Phase III study, EMBER-3, in participants with metastatic breast cancer in both monotherapy and in combination with Verzenio.

最後，在腫瘤學方面，正如我之前提到的，我們期待在 II 期劑量選擇後，於今年稍後將我們的 KRAS G12C 抑制劑 olomorasib 進入 III 期。最後，我們期待看到我們的 imlunetrant III 期研究 EMBER-3 的結果，該研究對患有轉移性乳腺癌的受試者進行單一療法和與 Verzenio 聯合療法。

This past year was busy and productive. And we expect more of the same in 2024 as we make meaningful progress advancing our pipeline for the benefit of patients. I'll now turn the call back to Dave for closing remarks.

過去的一年是忙碌而富有成效的。我們預計 2024 年會出現更多相同的情況，因為我們在推進我們的產品線方面取得了有意義的進展，造福於患者。現在我將把電話轉回給戴夫，讓他致閉幕詞。

Yes. Thanks, Dan, and congrats to you and the LRL team for a big year. Before we go to Q&A, let me briefly sum up our progress in the fourth quarter.

是的。謝謝 Dan，並恭喜你和 LRL 團隊度過了重要的一年。在進行問答之前，我先簡單總結一下我們第四季的進展。

Q4 revenue growth accelerated as our recently launched product portfolio continued to gain momentum. We achieved meaningful advances in our late-stage pipeline with the FDA approvals of Zepbound and Jaypirca. We continue to invest in recent and upcoming launches, late-stage medicines, early phase capabilities and in business development, all of which will serve as a foundation for future growth. In Q4, we completed the acquisition of POINT Biopharma and announced plans to build a new manufacturing site in Germany. We returned over $1 billion to shareholders via the dividend.

隨著我們最近推出的產品組合繼續獲得動力，第四季營收成長加速。隨著 Zepbound 和 Jaypirca 獲得 FDA 批准，我們在後期研發管線中取得了有意義的進展。我們繼續投資於最近和即將推出的產品、後期藥物、早期能力和業務發展，所有這些都將成為未來成長的基礎。第四季度，我們完成了 POINT Biopharma 的收購，並宣布計劃在德國建立新的生產基地。我們透過股息向股東返還超過 10 億美元。

Lastly, in January, we announced that Johna Norton, our Executive Vice President of Global Quality, will be retiring at the end of July after 34 years of service. During her tenure, Johna has overseen significant expansion, modernization and improvements in our quality and manufacturing processes. I'd like to thank her for her many years of outstanding service to Lilly.

最後，在一月份，我們宣布全球品質執行副總裁 Johna Norton 將在服務 34 年後於 7 月底退休。在任職期間，Johna 監督了我們品質和製造流程的重大擴張、現代化和改進。我要感謝她多年來為禮來公司提供的出色服務。

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

現在我將把電話轉給喬來主持我們的問答環節。

Thanks, Dave. Before diving into Q&A, I wanted to clarify one point. We may have had some muffled sound during announced prepared remarks regarding the timing of regulatory action on donanemab. And as Dan mentioned, the timing is expected to be Q1 of 2024 this year, received some notes that there were some muffled sound, so just wanted to clarify on that important point.

謝謝，戴夫。在進入問答之前，我想澄清一點。在宣布準備好的有關多納奈單抗監管行動時間的評論時，我們可能聽到了一些低沉的聲音。正如 Dan 所提到的，預計時間是今年 2024 年第一季度，收到一些註釋，聲音有些低沉，所以只是想澄清這一重要點。

Now for Q&A, we'd like to take questions from as many callers as possible and conclude the call in a timely manner. So consistent with prior quarters, we'll respond to one question per caller, so ask you limit to one question per caller as we'll end the call at 11:15 a.m. (Operator Instructions) Paul, please provide the instructions for the Q&A, and we're ready for the first caller.

現在進行問答環節，我們希望盡可能回答來電者的問題並及時結束通話。與前幾季一樣，我們將回答每個來電者一個問題，因此請您限制每個來電者只回答一個問題，因為我們將在上午11:15 結束通話（操作員說明）Paul，請提供問答說明，我們已準備好迎接第一個來電者。

(Operator Instructions) And the first question today is coming from Terence Flynn from Morgan Stanley.

（操作員說明）今天的第一個問題來自摩根士丹利的特倫斯·弗林（Terence Flynn）。

Congrats on the progress. Just wondering for your GLP franchise, ex U.S., you under-indexed versus your key competitor. Just wondering what are some of the hurdles to closing that gap as we think about the ramp in '24 but also into 2025?

祝賀取得的進展。只是想知道您的 GLP 特許經營權（美國除外）與您的主要競爭對手相比，您的指數較低。只是想知道，當我們考慮 24 年乃至 2025 年的成長時，縮小這一差距有哪些障礙？

Thanks, Terence, for the question. I'll hand over to Ilya Yuffa, President of Lilly International, for that question.

謝謝特倫斯提出這個問題。我將把這個問題交給禮來國際公司總裁伊利亞·尤法 (Ilya Yuffa)。

Thanks, Terence. As we think about Mounjaro launches outside the U.S., we have already launched in a number of select markets. We have foundation to be competitive in many of our markets. And we anticipate continued launches. We've just launched in vial format in select markets outside of the U.S., mainly in Australia, in Canada, in Germany and Poland.

謝謝，特倫斯。當我們考慮 Mounjaro 在美國以外的市場推出時，我們已經在許多選定的市場推出了。我們有基礎在許多市場上具有競爭力。我們預計將繼續推出。我們剛剛在美國以外的特定市場（主要是澳洲、加拿大、德國和波蘭）推出了小瓶包裝。

And we just received KwikPen approval in the U.K., and so we're anticipating launch there. As we get additional regulatory approvals for a multi-use KwikPen and we monitor our ramp-up in capacity for supply, we'll continue to launch in other markets throughout the year. And so we anticipate further growth, anticipated for launches of Mounjaro outside of the U.S. and continue with that throughout the year as well as into 2025.

我們剛剛在英國獲得了 KwikPen 的批准，因此我們預計會在英國推出。隨著我們獲得多用途 KwikPen 的更多監管批准，並且我們將監控供應能力的提升，我們將在全年繼續在其他市場推出產品。因此，我們預計 Mounjaro 在美國以外的推出將進一步成長，並持續到 2025 年。

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。

On Zepbound, it seems like you're making strong progress on coverage. But just interested in expectations for the remainder of this year as we think about just where coverage could go and just how to think about ASP. I guess, the core question is, is it reasonable to think that most payers who cover Wegovy will add Zepbound this year?

在 Zepbound 上，您似乎在覆蓋範圍方面取得了巨大進展。但我們只是對今年剩餘時間的預期感興趣，因為我們考慮了覆蓋範圍的走向以及如何考慮 ASP。我想，核心問題是，認為大多數覆蓋 Wegovy 的付款人今年都會添加 Zepbound 是否合理？

Thanks, Chris. I'll hand over to Patrik to comment on that question about Zepbound coverage.

謝謝，克里斯。我將請 Patrik 來評論有關 Zepbound 報導的問題。

Yes, thank you very much, Chris. As we stated, we are pleased we are so early in launch with 35% commercial access, having [contract this, I am seeing now]. Our efforts moving forward will really be to continue to expand payer access. But not only we will do that with a very disciplined approach as we did with Mounjaro, but also to make sure that we get to employer opt-in. And as Anat alluded to in her prepared remarks, that's going to take some time. But we are assuming that with the current access we have that our access will be along the lines of what the competition has referred to, around 50%.

是的，非常感謝你，克里斯。正如我們所說，我們很高興我們這麼早就推出了 35% 的商業訪問權，[合約這個，我現在看到了]。我們前進的努力實際上是繼續擴大付款人的使用範圍。但我們不僅會像對 Mounjaro 那樣採取非常嚴格的方法來做到這一點，而且還會確保我們得到雇主的選擇。正如阿納特在她準備好的演講中提到的那樣，這需要一些時間。但我們假設，根據目前的存取權限，我們的存取權限將與競爭對手所提到的一致，約為 50%。

Let me just emphasize that when it comes to employer opt-in, there is not one reliable source for employer opt-in. So I think that's something that we need to continue to monitor, and we'll come back with more data during coming earnings calls. So overall, a good start, and we will continue our efforts to increase payer access. I think we are quite encouraged with what we have heard from the marketplace so far. Employer opt-in will take longer, but we believe that we are well positioned in that regard as well.

我只想強調一下，當談到雇主選擇加入時，雇主選擇加入沒有一個可靠的來源。所以我認為這是我們需要繼續監控的事情，我們將在即將到來的財報電話會議上提供更多數據。總的來說，這是一個好的開端，我們將繼續努力增加付款人的准入。我認為我們對迄今為止從市場上聽到的消息感到非常鼓舞。雇主選擇加入將需要更長的時間，但我們相信我們在這方面也處於有利地位。

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。

Congrats on all the progress and the success here. But I just wanted to have a quick sense from Dan. Do you see a prospect from SYNERGY-NASH for Accelerated Approval? And can you confirm that while clinically significant, the secondary endpoint of fibrosis stage improvement was not statistically significant?

祝賀這裡取得的所有進展和成功。但我只是想從丹那裡快速了解一下。您是否看到 SYNERGY-NASH 加速審批的前景？您能否確認，雖然具有臨床意義，但纖維化階段改善的次要終點在統計上並不顯著？

Thanks, Seamus, for the question. Dan?

謝謝西莫的提問。擔？

Yes. Thanks, Seamus. This is really quite new to us, but we're really excited about it. We haven't had a chance yet to talk to the FDA here at all about next steps, but we're looking forward to having that opportunity. Of course, this was a small trial of about 190 participants, but it did use liver biopsies, of course, to assess the endpoints here.

是的。謝謝，西莫。這對我們來說確實很新鮮，但我們對此感到非常興奮。我們還沒有機會與 FDA 討論後續步驟，但我們期待有這樣的機會。當然，這是一項約有 190 名參與者的小型試驗，但它確實使用了肝臟活檢來評估終點。

With respect to the improvement in fibrosis, I think I probably previously stated that I was unsure whether it would be possible for incretin-based therapies to reverse fibrosis in patients based on competitor readouts in the field. But really excited to see this data with clinically meaningful improvement in fibrosis.

關於纖維化的改善，我想我之前可能說過，根據該領域競爭對手的讀數，我不確定基於腸促胰島素的療法是否有可能逆轉患者的纖維化。但很高興看到這些數據對纖維化有臨床意義的改善。

There's different doses. There's different statistical methods that can be applied here, accounting for dropouts, particularly in the placebo group. So we'll have to wait for the scientific presentation to see all the p-values there. But we're pretty positive on this data package as a whole and what this could mean for patients both in terms of stopping progression of MASH and reversing fibrosis.

有不同的劑量。這裡可以應用不同的統計方法來計算退出率，特別是在安慰劑組。因此，我們必須等待科學演示才能看到所有的 p 值。但我們對整個資料包非常樂觀，這對患者在阻止 MASH 進展和逆轉纖維化方面意味著什麼。

The next question is coming from Umer Raffat from Evercore.

下一個問題來自 Evercore 的 Umer Raffat。

Dave, as you think about manufacturing build-out in various sites, which is obviously very important for all the existing GLP demand, I'm curious, how are you balancing that dollar investment with your probabilities on orforglipron's clinical and commercial, especially with all the blinded data that's coming in?

戴夫，當您考慮在不同地點進行製造擴建時，這顯然對所有現有的 GLP 需求非常重要，我很好奇，您如何平衡美元投資與 orforglipron 臨床和商業的可能性，特別是與所有傳入的盲數據？

Thanks, Umer. Dave?

謝謝，烏默。戴夫？

Yes, happy to answer that. Of course, as we enter this phase of really strong growth in the incretins, we're very focused on allocating capital. But top priority is creating new capacities. The gating factors are not really financial for us right now, so you can expect us to be investing fully. We're not slowing down because of cash flow or whatever. It's really a function of the technical capacities both in people and in suppliers to be able to bring facilities online. That's particularly true in the parenteral side.

是的，很高興回答這個問題。當然，當我們進入腸促胰島素真正強勁成長的階段時，我們非常注重資本配置。但首要任務是創造新能力。目前，限制因素對我們來說並不是真正的財務因素，因此您可以期望我們進行充分投資。我們不會因為現金流或其他什麼原因而放慢腳步。能夠使設施上線實際上取決於人員和供應商的技術能力。在註射方面尤其如此。

Now you're referencing orforglipron. Here, we do plan to build ahead of Phase III at risk. I think, given the probability we assess internally as well as the opportunity on the other side of a positive Phase III, we see that as a wise investment. And as we've commented on before, it relies, as you would know, on very different assets inside Lilly as well as outside of Lilly. So here, you have organic chemistry, API and tablets and capsules, so a pretty different setup.

現在您正在引用 orforglipron。在這裡，我們確實計劃在第三階段之前進行建設，但存在風險。我認為，考慮到我們內部評估的可能性以及第三階段積極的另一面的機會，我們認為這是一項明智的投資。正如我們之前評論過的，正如您所知，它依賴於禮來內部和禮來外部截然不同的資產。所以在這裡，你有有機化學、API 以及片劑和膠囊，所以這是一個非常不同的設定。

So we can -- we're paralleling that with our robust injectable investments. And if we're wrong, okay, we'll have to eat that in the end if orforglipron isn't a strong product. But if it is, I think it does begin to change the math on supply in this category. And I think that's about worth taking.

所以我們可以——我們將其與我們強勁的可注入投資並行。如果我們錯了，好吧，如果 orforglipron 不是一個強大的產品，我們最終將不得不吃掉它。但如果是的話，我認為它確實開始改變這個類別的供應數學。我認為這是值得採取的。

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

下一個問題來自沃爾夫研究中心的蒂姆·安德森。

On SURPASS-CVOT, you mentioned it slipped to 2025. I assume that implies the one interim look has come and gone. And then you're evaluating both non-inferiority and superiority. Would you agree that superiority is really what you need to show here and what you're confident in achieving that?

在 SURPASS-CVOT 上，您提到它會推遲到 2025 年。我認為這意味著一個臨時外觀已經來了又走了。然後你要評估非劣效性和優越性。您是否同意，您確實需要在這裡展示優越性，並且您有信心實現這一點？

Thanks, Tim, for those couple of questions. Maybe we'll field the one on the interim look, Dan?

謝謝蒂姆提出這幾個問題。也許我們會派出臨時造型的那個，丹？

Yes, sure. Well, thanks for that question, Tim. As you know, Lilly doesn't comment on interims. Probably most trials in our portfolio do have opportunities for interim looks. But that has -- is not, I think, germane at all to the question on the timing on clintrials.gov, which was before and continues to be the time point at which we'll have final data.

是的，當然。嗯，謝謝你提出這個問題，提姆。如您所知，禮來公司不會對中期業績發表評論。也許我們投資組合中的大多數試驗確實都有臨時觀察的機會。但我認為，這與 clintrials.gov 上的時間安排問題完全沒有關係，該時間點以前是，現在仍然是我們獲得最終數據的時間點。

When we initially put that time point in clinicaltrials.gov, it was in early 2020, we hadn't started enrolling the trial yet so that was based on our assumption on enrollment rates but probably more importantly on event rates. And as the trial matures, we get a view on event rate.

當我們最初在 ClinicalTrials.gov 上發布該時間點時，是在 2020 年初，我們尚未開始招募試驗，因此這是基於我們對註冊率的假設，但可能更重要的是基於事件發生率。隨著試驗的成熟，我們可以了解事件發生率。

So I know it's frustrating for investors and for us perhaps to wait to longer time to get events. But of course, that's great news for patients when the event rates are slower, remembering that this is a head-to-head trial with a drug, Trulicity, that we already know is active in preventing MACE events.

所以我知道這對投資者和我們來說可能會等待更長的時間才能獲得事件感到沮喪。當然，當事件發生率較慢時，這對患者來說是個好消息，請記住，這是一項藥物 Trulicity 的頭對頭試驗，我們已經知道該藥物在預防 MACE 事件方面具有積極作用。

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。

Congrats on the progress. I have a question regarding your sleep apnea study. How much benefit do you think from baseline is required for this to be clinically meaningful? Is it 50% or more? And do you think the trial is big enough to seek a label in sleep apnea?

祝賀取得的進展。我有一個關於您的睡眠呼吸中止症研究的問題。您認為需要從基線獲得多少好處才能具有臨床意義？是50%還是更多？您認為該試驗規模是否足夠大，足以為睡眠呼吸中止症貼上標籤？

Thanks, Mohit, for the question. Dan, back to you.

謝謝莫希特提出的問題。丹，回到你身邊。

Yes, thanks. There isn't really a well-established threshold for clinical meaningfulness in sleep apnea. Of course, the commonly used measure here is an index of how many apneic or hypoxic events a patient has while sleeping. Certainly, drugs in this category, I think, have great potential to improve that.

對了謝謝。睡眠呼吸中止症的臨床意義並沒有一個明確的閾值。當然，這裡常用的衡量標準是患者在睡眠時發生呼吸中止或缺氧事件的次數的指標。當然，我認為這一類藥物有很大的潛力來改善這一點。

We're excited to see what tirzepatide can see. Probably in addition to the absolute percent improvement in AHI that we'll be looking for, I'd also like to see patients switching from one category, for example, intermediate to mild disease or things like that. So we'll be looking at a number of things to assess clinical meaningfulness here, but I'm quite optimistic.

我們很高興看到替澤帕肽能看到什麼。可能除了我們要尋找的 AHI 的絕對改善百分比之外，我還希望看到患者從一種類別（例如，中度疾病）轉變為輕度疾病或類似情況。因此，我們將研究許多因素來評估臨床意義，但我非常樂觀。

The next question is from Louise Chen from Cantor.

下一個問題來自 Cantor 的 Louise Chen。

I wanted to ask you how you think about sizing the downstream opportunities for GLP-1, such as tirzepatide, maybe in NASH, some of the other indications that you're going after as well.

我想問您如何考慮調整 GLP-1 的下游機會，例如替澤帕肽，可能在 NASH 中，以及您也在尋找的其他一些適應症。

Thanks, Louise, for that question. So about the downstream opportunities in NASH and elsewhere, Patrik, do you want to field that?

謝謝路易絲提出這個問題。那麼關於 NASH 和其他地方的下游機會，派崔克，你想利用它嗎？

Thank you very much. I think there are two important aspects. The first one is when we refer to employer opt-in, I think employees are really looking actively into benefits of listing anti-obesity medications. And whatever data we can generate here being in the cardiovascular space, being in OSA or being in NASH, average indications will be extremely important for increased employer opt-in.

非常感謝。我認為有兩個重要面向。第一個是當我們提到雇主選擇加入時，我認為員工確實在積極研究列出抗肥胖藥物的好處。無論我們在心血管領域、OSA 或 NASH 領域能夠產生什麼數據，平均適應症對於增加雇主的選擇都極為重要。

The second piece will be in Medicare Part D. As long as TROA is not passed, I think data in those co-morbidities will be critical to enable access for patients in Medicare Part D. So those are truly the key drivers for those indications.

第二部分將在 Medicare D 部分。只要 TROA 未通過，我認為這些合併症的數據對於使患者能夠獲得 Medicare D 部分至關重要。因此，這些確實是這些適應症的關鍵驅動因素。

The next question is coming from Kerry Holford from Berenberg.

下一個問題來自貝倫貝格的克​​里·霍爾福德。

It's on tirzepatide obesity. I'm interested to hear why you've taken the decision not to launch under the Zepbound brand outside the U.S. but rather seek a label expansion for weight loss for Mounjaro. Does that relate to simplicity, perhaps faster reimbursement access? And I wonder if you foresee any risk here that ex U.S. governments prefer ultimately to keep diabetes and obesity budgets separate.

這是關於替西帕肽肥胖。我很想知道為什麼你們決定不在美國以外的地區推出 Zepbound 品牌，而是尋求 Mounjaro 減肥品牌的擴張。這是否與簡單、或許更快的報銷管道有關？我想知道您是否預見到美國前政府最終傾向於將糖尿病和肥胖預算分開的任何風險。

Thank you, Kerry, for the questions. I'll hand over to Ilya to talk about the branding of tirzepatide OUS.

謝謝克里提出的問題。我將交給 Ilya 來談談替澤帕肽 OUS 的品牌。

Sure. Yes, so the broader tirzepatide outside of the U.S., it depends on a number of different factors, whether it's regulatory or competitor market dynamics. There are some payer dynamics as well. We don't anticipate that being a challenge in terms of negotiating reimbursement either for type 2 diabetes or for chronic weight management. We continue to have those discussions in a number of markets and are optimistic about our ability to commercialize under different brand scenarios.

當然。是的，因此美國以外更廣泛的替西帕肽取決於許多不同的因素，無論是監管還是競爭對手的市場動態。還有一些付款人動態。我們預計這對於第 2 型糖尿病或長期體重管理的報銷談判不會構成挑戰。我們繼續在多個市場進行這些討論，並對我們在不同品牌場景下的商業化能力感到樂觀。

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。

Dave, I know you guys formally announced LillyDirect last fall. Should we view it as a platform to just streamline access to providers and Lilly meds? Or is there a monetization model or some market differentiation that could also play out over time?

Dave，我知道你們去年秋天正式宣布了 LillyDirect。我們是否應該將其視為一個簡化對提供者和禮來藥物的獲取的平台？或者是否存在一種貨幣化模式或一些市場差異化也可能隨著時間的推移而發揮作用？

For the question, I can start, Patrik, jump in. Yes, thanks for the question. The idea was really actually borne out of the challenges patients face every day in the U.S. in sometimes seeing doctors. And you'll know we have a doctor finder tool as well as telehealth partners on the platform for migraine, diabetes and obesity. Finding medicines and their pharmacies, that's been a challenge. And I think particularly as supplies are tight, many patients report driving to five, six, seven pharmacies to find the medicine they need. Well, this simplifies that process.

對於這個問題，我可以開始了，派崔克，插話。是的，謝謝你的提問。這個想法其實是源自於美國患者每天在看醫生時所面臨的挑戰。您會知道，我們在偏頭痛、糖尿病和肥胖症平台上擁有醫生查找工具以及遠距醫療合作夥伴。尋找藥物及其藥房是一個挑戰。我認為，特別是在供應緊張的情況下，許多患者報告開車去五、六、七家藥局尋找他們需要的藥物。嗯，這簡化了這個過程。

And then I think, in addition, there's been a lot of noise about drugs that are illicit or copies or compounded versions of Zepbound or other weight loss drugs. And that's concerning to us. And I think it's concerning to patients. So by going to LillyDirect literally, they have confidence in the supply. And finally, application of our savings programs has also been a challenge at the pharmacy counter. And that happens 100% of the time on LillyDirect.

此外，我認為還有很多關於非法藥物、Zepbound 或其他減肥藥物的複製品或複合版本的噪音。這與我們有關。我認為這與患者有關。因此，透過字面上的 LillyDirect，他們對供應充滿信心。最後，在藥局櫃檯應用我們的儲蓄計畫也是一個挑戰。在 LillyDirect 上，這種情況 100% 都會發生。

We haven't thought about it as a way to create some new retail distribution business. It's a way to serve the patients that want our medicines better. That's sort of the frame we're in now. Early days, we're trying to develop it to be smoother, better, include more products over time, have better information about physicians and telehealth providers. So look for more developments there. But good start so far, a lot of energy and enthusiasm from the patient community.

我們還沒有考慮將其作為創建新零售分銷業務的一種方式。這是為那些需要我們更好的藥物的患者提供服務的一種方式。這就是我們現在所處的框架。在早期，我們正在努力將其開發得更流暢、更好，隨著時間的推移包括更多產品，提供有關醫生和遠距醫療提供者的更好資訊。因此，尋找更多的發展。但到目前為止，這是一個良好的開端，來自患者社區的大量精力和熱情。

The next question is coming from David Risinger from Leerink.

下一個問題來自 Leerink 的 David Risinger。

Congrats on today's updates. So my question is for Dave and Dan on lean muscle loss associated with incretin use. Could you help us understand Lilly's take on this debate and comment on tirzepatide's data to date relative to semaglutide? What I've observed is that SURMOUNT-1 showed a 3:1 lean muscle loss ratio whereas sema's STEP-1 trial showed a 1.5:1 ratio, albeit with a slightly different assessment.

恭喜今天的更新。所以我的問題是向 Dave 和 Dan 詢問與使用腸促胰素相關的瘦肌肉損失。您能否幫助我們了解禮來公司對這場辯論的看法，並對迄今為止相對於索馬魯肽的替澤帕肽數據進行評論？我觀察到，SURMOUNT-1 顯示 3:1 的瘦肌肉損失比率，而 sema 的 STEP-1 試驗顯示 1.5:1 的比率，儘管評估略有不同。

Thanks, Dave. I'll have Dan field that.

謝謝，戴夫。我會讓丹·菲爾德來。

Yes, thanks for your question. Maybe just starting with our take on lean versus fat mass, I think the ratio of lean to fat mass is an important thing to think about. Body composition, not just by weight, matters to patients. For example, in risk of type 2 diabetes or cardiovascular disease, that body ratio seems to be important.

是的，謝謝你的提問。也許從我們對瘦肉量與脂肪量的看法開始，我認為瘦肉量與脂肪量的比率是一個需要考慮的重要問題。身體組成對患者來說很重要，而不僅僅是體重。例如，對於第 2 型糖尿病或心血管疾病的風險，身體比例似乎很重要。

The good news is that for patients on tirzepatide, that ratio appears to improve. As you pointed out, they lose far more fat mass than lean mass. And so in every trial we've done, at the end of the trial, if we measure body composition, it's better, a higher ratio of lean to fat than at the beginning of the trial. So we see this change in body composition as a benefit, a potential benefit of tirzepatide to be further explored.

好消息是，對於服用替西帕肽的患者來說，這一比例似乎有所改善。正如您所指出的，他們失去的脂肪量遠遠多於瘦肉量。因此，在我們所做的每一次試驗中，在試驗結束時，如果我們測量身體成分，那麼瘦肉與脂肪的比例會比試驗開始時更高。因此，我們將身體組成的這種變化視為一種益處，這是替西帕肽的一個潛在益處，有待進一步探索。

Of course, it's also a benefit we want to further extend. You've seen us try to improve the total amount of body weight loss. We're also trying to improve -- further improve, I should say, the change in body mass composition. And that's why you saw us acquire Versanis and experiment with drugs like bimagrumab.

當然，這也是我們想要進一步擴展的福利。您已經看到我們嘗試改善體重減輕的總量。我們也試圖改善——我應該說，進一步改善體重成分的變化。這就是為什麼我們收購了 Versanis 並試驗 bimagrumab 等藥物。

The number you quote from the tirzepatide and semaglutide studies seem right to me. Of course, they're not head-to-head studies. But it does raise a question here about whether there's a potential benefit of GIP-1 -- GIP agonism here in addition to GLP-1 agonism. That's probably the way I would interpret this data.

您從替西帕肽和索馬魯肽研究中引用的數字對我來說似乎是正確的。當然，它們不是面對面的研究。但它確實提出了一個問題，即除了 GLP-1 激動之外，GIP-1 是否還有潛在的益處——GIP 激動。這可能就是我解釋這些數據的方式。

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。

I would love to get your take on how you're thinking about the opportunity for the oral GLP-1s. We've seen some mixed data from competitors. And I just would love to get how you see this evolving in context of your investment in orforglipron.

我很想了解您對口服 GLP-1 機會的看法。我們從競爭對手那裡看到了一些好壞參半的數據。我只是想知道您在投資 orforglipron 的背景下如何看待這種演變。

Thanks, Evan, for the question. Patrik, maybe how about you talk about how we think about an oral agent?

謝謝埃文提出的問題。派崔克（Patrik），也許你能談談我們對口服製劑的看法？

Thank you very much. When we look at the opportunity in obesity, we have more than 110 million in the U.S. We have 650 million globally. I think taking into account the current supply constraints across markets, it's impossible to reach all of those with injectables. So I think that's the big opportunity we have for orforglipron.

非常感謝。當我們審視肥胖問題的機會時，我們發現美國有超過 1.1 億人，全球有 6.5 億人。我認為考慮到目前整個市場的供應限制，不可能向所有的人提供注射劑。所以我認為這對 orforglipron 來說是一個巨大的機會。

And what we have seen so far in Phase II, if we can replicate those data in Phase III, we have an oral medicine here with a weight loss along the lines of the best competitive incretin, not at the level of tirzepatide, but at the level of the best incretin in the marketplace and with no food or water restrictions. So we really see the opportunity here with orforglipron to reach patients across the globe.

到目前為止，我們在第二階段所看到的，如果我們可以在第三階段複製這些數據，我們這裡有一種口服藥物，其減肥效果與最具競爭力的腸降血糖素相似，不是達到替澤帕肽的水平，而是達到市場上最好的腸促胰島素水平，並且沒有食物或水的限制。因此，我們確實看到了 orforglipron 接觸全球患者的機會。

And there is another component as well. If we look at the current market, approximately 20% of patients with obesity are actually concerned to take an injectable. So that's another opportunity with orforglipron. So we believe that's a really strong core in our hands moving forward in the space of chronic weight management.

還有另一個組件。如果我們看看目前的市場，大約 20% 的肥胖患者實際上擔心注射藥物。這是 orforglipron 的另一個機會。因此，我們相信這是我們在長期體重管理領域前進的真正強大的核心。

Next question is from Steve Scala from Cowen.

下一個問題來自 Cowen 的 Steve Scala。

There could be several reasons why Lilly is not initiating a Phase III trial of tirzepatide in NASH. First, Lilly believes it has better molecules. Second, there is something in the Phase II data which is less than ideal. Or third, Lilly will do a Phase III, it just hasn't gotten around to finalizing plans.

禮來公司沒有啟動替澤帕肽治療 NASH 的 III 期試驗可能有多種原因。首先，禮來公司相信它有更好的分子。其次，二期數據有些不太理想。或者第三，禮來公司將進行第三階段，但還沒有時間敲定計畫。

But that really can't be yet. To draw a parallel, you're starting a Phase III with LPA without even telling us the Phase II was positive. So what would be best for us to conclude about tirzepatide in NASH?

但這確實還不可能。打個比方，你在 LPA 中開始了第三階段，甚至沒有告訴我們第二階段的結果是正面的。那麼，對於 Tirzepatide 在 NASH 中的作用，我們最好得出什麼結論呢？

Yes. No, thanks, Steve, for the clever analysis here. So first of all, I should just say we literally just got this Phase II data, so give us a chance to determine our next steps on plans to probably debunk at least one of the hypotheses here. There's nothing bad in the data that would stop us from going to Phase III.

是的。不，謝謝史蒂夫的巧妙分析。首先，我應該說我們實際上剛剛獲得了第二階段的數據，所以給我們一個機會來確定我們的下一步計劃，以可能揭穿至少一個假設。數據中沒有任何問題會阻止我們進入第三階段。

In terms of having a better molecule, probably we do in retatrutide. Of course, we don't have that kind of Phase II data here for retatrutide. So that's based on liver fat reduction, which was just incredible in the Phase II trial. Still though, I think having a positive Phase II trial here with really a meaningful data in NASH obligates us to think about next steps. As I said, that's going to the FDA to talk to them.

就擁有更好的分子而言，我們可能會使用瑞他魯肽。當然，我們這裡沒有瑞他魯肽的那種 II 期數據。這是基於肝臟脂肪減少的結果，這在第二階段試驗中是令人難以置信的。儘管如此，我認為在 NASH 方面進行積極的 II 期試驗並獲得真正有意義的數據使我們有義務考慮下一步。正如我所說，我們將去 FDA 與他們交談。

I would say in terms of planning a Phase III for any drug in NASH, a really important priority for us is to move away as much as we can from liver biopsies and replace them with noninvasive testing. I think we and others in the field have made a lot of progress there. We see analogies here to other disease areas. And we hope that in the future, it will be possible to conduct Phase III NASH trials without relying on biopsies.

我想說的是，在規劃 NASH 任何藥物的 III 期臨床試驗時，對我們來說真正重要的優先事項是盡可能擺脫肝臟活檢，並用非侵入性檢測取代它們。我認為我們和該領域的其他人已經在這方面取得了很大進展。我們在這裡看到了與其他疾病領域的類比。我們希望未來能夠在不依賴活檢的情況下進行 NASH III 期試驗。

That would really have a profound effect on the feasibility of running these trials quickly but also in the clinical application of NASH drugs, where those noninvasive biomarkers could be used to identify patients for treatment and monitor response to therapy rather than biopsies.

這確實會對快速運行這些試驗的可行性產生深遠的影響，而且也會對NASH 藥物的臨床應用產生深遠的影響，這些生物標記可用於識別患者進行治療並監測對治療的反應，而不是活檢。

The next question is from Chris Shibutani from Goldman Sachs.

下一個問題來自高盛的 Chris Shibutani。

Duration of use of the GLP-1s across the diabetes and obesity populations, previously, you've characterized the duration in the range of 15 months for diabetes and have commented that you don't believe we have enough experience. Any updates there? And when do you think we will have enough experience to be able to get a better gauge of duration of use median in the obesity population at least initially?

GLP-1 在糖尿病和肥胖人群中的使用持續時間，之前，您描述了糖尿病的持續時間在 15 個月範圍內，並評論說您認為我們沒有足夠的經驗。有更新嗎？您認為我們什麼時候才能擁有足夠的經驗，至少在最初階段能夠更好地衡量肥胖者的使用時間中位數？

Thanks, Chris. Patrik, do you want to comment on duration of therapy?

謝謝，克里斯。派崔克，您想對治療持續時間發表評論嗎？

Yes. Thank you very much, Chris. I think you're right. It's quite challenging. It's still early days with both Mounjaro and particularly Zepbound. And we have been facing some specific dynamics in terms of supply and also changes to the co-pay program. However, when we look at the recent data for Mounjaro, it's encouraging. And it suggests that patients that start their therapy back in Q1 2023 are having a persistency at least along the lines of other injectable incretins.

是的。非常感謝你，克里斯。我想你是對的。這是相當具有挑戰性的。對於 Mounjaro，特別是 Zepbound，現在還處於早期階段。我們一直面臨著供應方面的一些具體動態以及共同支付計劃的變化。然而，當我們查看 Mounjaro 最近的數據時，這是令人鼓舞的。這表明，在 2023 年第一季開始治療的患者至少與其他注射腸促胰島素一樣具有持久性。

For Zepbound, definitely too early. But we strongly believe that patients will be motivated when they see the benefits of the drug. And there will, of course, be many factors there impacting both supply, macroeconomic and microeconomic. But we are convinced that there will be a final duration of treatment also for obesity since when we look into even heart failure and type 2 diabetes, more than a 12-month period of adherence is considered long.

對於 Zepbound 來說，絕對為時過早。但我們堅信，當患者看到該藥物的好處時，他們會受到激勵。當然，會有很多因素影響供給、宏觀經濟和微觀經濟。但我們相信肥胖症也有最終的治療期限，因為當我們研究心臟衰竭和第 2 型糖尿病時，超過 12 個月的堅持期就被認為是很長的。

But encouraging data in type 2 diabetes so far. And with Zepbound, we will see that will for sure be an end of duration based upon what we have seen in other chronic diseases. But we believe that the features itself will be motivating for patients.

但迄今為止，2 型糖尿病的數據令人鼓舞。透過 Zepbound，根據我們在其他慢性疾病中所看到的情況，我們將看到這肯定會結束。但我們相信這些功能本身就會激勵患者。

The next question is coming from Akash Tewari from Jefferies.

下一個問題來自 Jefferies 的 Akash Tewari。

So David, at JPMorgan, you made an interesting comment on orforglipron, where you mentioned the molecule has lots to prove here. Can you elaborate a bit on what you mean by this? And what's your confidence on orfo's DDI profile? It seems to have a bit of CYP3A4 inhibition. So will this drug be able to get dosed with SGLT2s, given they were excluded in some of your earlier studies?

摩根大通的大衛，您對 orforglipron 做了有趣的評論，您提到該分子在這裡有很多需要證明的地方。能詳細說明一下您的意思嗎？您對 orfo 的 DDI 概況有何信心？它似乎有一點CYP3A4抑製作用。那麼，鑑於 SGLT2 在您早期的一些研究中被排除在外，這種藥物是否能夠與 SGLT2 一起服用？

Sorry, that was for me? Although I could frame like why I said that, but maybe Dan can get on the specific DDI question and SGLT2 coadministration. I just said that because we're just starting the Phase III. And we all know small molecule, there's a bit of empiricism in terms of eliminating safety risk. And of course, every day, as we expose more patients to the drug and we have higher doses, that's a good day where we don't announce that the drug has a problem.

抱歉，那是給我的？雖然我可以解釋為什麼我會這麼說，但也許 Dan 可以解決特定的 DDI 問題和 SGLT2 共同給藥。我這麼說是因為我們剛開始第三階段。我們都知道小分子，在消除安全風險方面存在一些經驗主義。當然，每天，當我們讓更多的患者接觸這種藥物並且我們的劑量更高時，這是我們不宣布該藥物有問題的好日子。

At some point, we reach a lot of confidence. We just weren't at that point. We're not at it now. I think we're running the Phase III experiment, and we need to discharge the off-target safety that is inherent in small molecule discovery. And we've seen in this class from others. But nothing specific on my mind. Maybe Dan can further reassure us.

在某些時候，我們會充滿信心。我們只是還沒到那個時候。我們現在還沒到那一步。我認為我們正在進行第三階段實驗，我們需要消除小分子發現中固有的脫靶安全性。我們在這堂課上從其他人那裡看到了。但我心裡沒有什麼具體的想法。也許丹可以進一步讓我們放心。

Yes. Thanks, Dave. Of course, so just the normal Phase III types of risk, new safety signals, which could always arise. I think with respect to DDI and coadministration with SGLT2s, we expect that to be possible. And we have that ongoing in our Phase III trials. There are patients who achieve -- will be dosed with -- are being dosed with orforglipron as well as other drugs like SGLT2s.

是的。謝謝，戴夫。當然，只是正常的第三階段風險，新的安全訊號總是可能出現。我認為就 DDI 以及與 SGLT2 的聯合用藥而言，我們希望這是可能的。我們正在進行第三階段試驗。有些患者已經達到目標，即將接受治療，正在接受 orforglipron 以及其他藥物（如 SGLT2）治療。

The next question is from Trung Huynh from UBS.

下一個問題來自瑞銀集團的 Trung Huynh。

Can I just ask your thoughts on GIP agonism versus antagonism, given data yesterday from a competitor suggesting more limited effects on things like blood pressure and lipid modifications? Just how differentiated do you think an agonism approach is versus antagonism and why you think agonism is the way forward?

鑑於昨天來自競爭對手的數據表明 GIP 對血壓和血脂改變等方面的影響更為有限，我能否問一下您對 GIP 激動與拮抗的看法？您認為激動方法與對抗方法有何不同？為什麼您認為激動方法是前進的方向？

Dan?

擔？

Yes. Well, first of all, it's an unfair comparison. We have so much data now on the benefits of GIP agonism from tens of thousands of participants in randomized clinical trials for tirzepatide. So we're extremely confident here about the benefits of GIP agonism. Adding to that data, we have experimented with a pure GIP agonist that doesn't have any GLP-1, and we reported the benefits there in our Phase I study.

是的。嗯，首先，這是一個不公平的比較。我們現在有大量來自替澤帕肽隨機臨床試驗參與者的 GIP 激動益處的數據。因此，我們對 GIP 激動劑的益處非常有信心。除了這些數據之外，我們還嘗試了不含任何 GLP-1 的純 GIP 激動劑，並在第一階段研究中報告了其益處。

We're contrasting that here to a small Phase I study that was recently published with a drug that has both GLP-1 agonism and GIP antagonism. I noted in that publication, the GIP antagonism is at a much lower affinity. So it probably only starts to antagonize GIP at very high doses. It's probably a question for that company.

我們將其與最近發表的一項小型 I 期研究進行對比，該研究使用了一種同時具有 GLP-1 激動和 GIP 拮抗作用的藥物。我在那篇出版品中指出，GIP 拮抗作用的親和力要低得多。因此，它可能只有在非常高的劑量時才開始拮抗 GIP。這可能是該公司的問題。

But I noted at the high doses actually an increase in free fatty acids and complete attenuation of the decrease in triglycerides in the clinical trial. Those are some effects that we attribute to GIP. And so I'm not surprised that antagonism of GIP is starting to have some negative effects once that kicks in.

但我注意到，在臨床試驗中，高劑量實際上會增加遊離脂肪酸，並完全減弱三酸甘油酯的下降。這些是我們歸因於 GIP 的一些影響。因此，一旦 GIP 的拮抗作用開始產生一些負面影響，我並不感到驚訝。

We also see GIP agonism as having positive benefits on tolerability, reducing potentially nausea and vomiting. Then again, I think maybe at the higher doses, you could probably see some hints of the opposite effect with antagonism. So pretty glad with the decision we took. And let's see how the field continues to evolve.

我們也認為 GIP 激動劑對耐受性有積極的好處，可以減少潛在的噁心和嘔吐。話又說回來，我認為也許在較高劑量下，您可能會看到一些與拮抗作用相反的效果的跡象。對我們所做的決定感到非常高興。讓我們看看這個領域如何繼續發展。

The next question is from Carter Gould from Barclays.

下一個問題來自巴克萊銀行的卡特·古爾德。

I guess, over the prior two earnings calls, there have been at least an acknowledgment that CMOs were going to be part of the equation going forward for supply on the incretin side. I guess, does the development seen yesterday have any sort of direct or indirect impacts as you think about that part of the equation going forward?

我想，在前兩次財報電話會議上，至少有人承認 CMO 將成為腸促胰素方面未來供應等式的一部分。我想，當您考慮未來方程式的這一部分時，昨天看到的發展是否會產生任何直接或間接的影響？

Thanks, Carter. Anat, do you want to field that?

謝謝，卡特。阿納特，你想派出那個嗎？

Sure. So we've -- and I've mentioned on this call as well that we have very extensive expansion agenda, which does include third parties. While our strategy is and has always been to develop more internally, we do have third parties as well. So yes, we saw the announcement that came out from Novo yesterday regarding the intent to acquire Catalent. And we certainly have questions about that transaction and need to learn more.

當然。所以我們——我也在這次電話會議上提到過，我們有非常廣泛的擴張議程，其中確實包括第三方。雖然我們的策略始終是在內部進行更多開發，但我們也有第三方。所以，是的，我們昨天看到了 Novo 發布的有關收購 Catalent 意圖的公告。我們當然對該交易有疑問，需要了解更多資訊。

And we all know Catalent is an integral part or a manufacturer of both commercial and pipeline products for the industry, especially in diabetes and obesity. And we have products with these sites as well. So our focus today is on ensuring that continuity of supply of medicine for patients is uninterrupted as well as we intend on holding Catalent accountable to their contract with us as we look and we gain more information on this proposed transaction.

我們都知道康泰倫特是該行業商業和管道產品的重要組成部分或製造商，特別是在糖尿病和肥胖症領域。我們也有這些網站的產品。因此，我們今天的重點是確保為患者提供藥品的連續性不受干擾，並且我們打算讓康泰倫特對他們與我們簽訂的合約負責，因為我們正在研究並獲得有關這項擬議交易的更多信息。

The next question is coming from James Shin from Deutsche Bank.

下一個問題來自德意志銀行的 James Shin。

I just want to circle back to Carter's question. Given Lilly is well-capitalized and manufacturing capacity being the priority, I mean, could you expect more buy versus build to get around some of the technical bottlenecks and the nontrivial FDA process? I just want to get your thoughts there.

我只想回到卡特的​​問題。鑑於禮來公司資本充足且生產能力是首要任務，我的意思是，您是否可以期望更多的購買而不是構建來繞過一些技術瓶頸和重要的 FDA 流程？我只是想了解你的想法。

Dave?

戴夫？

Yes, maybe I'll give it a shot. Thanks for the question, James. Yes, as I mentioned on the earlier question related to orforglipron, we are not -- we don't think of ourselves as capital-constrained buying or building in the space. The reality is there just isn't built capacity that's available. Most of it that's being used is already deployed against the leading products in the GLP-1 space, at least any at scale. And new capacity has a lead time of 3 to 4 years.

是的，也許我會試試看。謝謝你的提問，詹姆斯。是的，正如我在之前與 orforglipron 相關的問題中提到的，我們不是——我們不認為自己是該領域的資本受限購買或建造者。現實情況是，根本沒有可用的可用容量。正在使用的大部分技術已經部署在 GLP-1 領域的領先產品中，至少是大規模部署的。而新增產能的交付週期為3至4年。

So all of the things that are coming online now, like we mentioned today our very large site in Concord, North Carolina, that's a big node of capacity for the sector and certainly for Lilly. I mean, that was announced 2.5 years ago. And it will just begin production at the end of this year. So that's the problem.

因此，現在所有正在上線的東西，就像我們今天提到的位於北卡羅來納州康科德市的大型網站一樣，這對該行業來說是一個重要的容量節點，當然對於禮來公司來說也是如此。我的意思是，這是 2.5 年前宣布的。它將於今年年底開始生產。這就是問題所在。

And why is that? Well, of course, greenfield building is difficult. Repurposing is difficult. But also these are technically complex facilities. There's not an infinite number of people who know how to set them up. And the supply chain for the machines that make the products is also constrained.

為什麼是這樣？當然，綠地建設是很困難的。重新利用是很困難的。但這些設施在技術上也很複雜。知道如何設置它們的人並不多。製造產品的機器的供應鏈也受到限制。

So at this point, I don't think there's an easy way forward. And I think even in yesterday's announcements, we have a lot of questions about that. But I think even the purchaser or our competitor said it will take many years for them to be able to increase capacity within that purchase.

所以在這一點上，我認為沒有一個簡單的方法。我認為即使在昨天的公告中，我們對此也有很多疑問。但我認為，即使是購買者或我們的競爭對手也表示，他們需要很多年才能在購買中增加產能。

So it's just not an easy problem to solve. I think that over time, it will ease. There will be more capacity brought online by us, our competitor and maybe others, including third parties. And new technology will emerge like orforglipron or other oral options that tap into a different asset bases.

所以這不是一個容易解決的問題。我認為隨著時間的推移，這種情況會緩解。我們、我們的競爭對手以及其他人（包括第三方）將會提供更多的線上容量。新技術將會出現，例如 orforglipron 或其他利用不同資產基礎的口服藥物。

So I know it's frustrating for investors, it's frustrating for us. It's even more frustrating for patients. But it's just sort of the situation were in as there will be steady gains in manufacturing over the coming several years and perhaps bigger gains after that.

所以我知道這讓投資人感到沮喪，也讓我們感到沮喪。對患者來說，這更令人沮喪。但這只是目前的情況，因為未來幾年製造業將穩定成長，之後可能會有更大的成長。

Next question is from Rajesh Kumar from HSBC.

下一個問題來自匯豐銀行的 Rajesh Kumar。

Can you give us some color on how the access with employers is playing out? Are you getting exclusive access for your drugs or you're being added to the existing access your competitors' drugs have? And what is the nature of discussion, especially given that Zepbound is priced at a more attractive list price? I'm assuming with rebate, differences might be a little bit smaller. But any color there might be super helpful.

您能為我們介紹一下雇主的進入情況如何嗎？您是否獲得了藥品的獨家使用權，或者您被添加到競爭對手藥品的現有使用權中？討論的本質是什麼，特別是考慮到 Zepbound 的定價更具吸引力？我假設有了回扣，差異可能會小一點。但任何顏色都可能非常有幫助。

Yes, thanks, Rajesh. I think we covered that on Chris Schott's question earlier. I don't know if Patrik would have anything to add or if we could just move on.

是的，謝謝，拉傑什。我想我們之前已經在克里斯·肖特的問題上討論過這一點。我不知道帕特里克是否有什麼要補充的，或者我們是否可以繼續前進。

No, I think the only addition would be that we are always aiming for open access. We believe that's important for the providers and patients we are serving. So that's going to be our aim when it comes to employer opt-in as well. And we believe the move by pricing Zepbound 22% below the competition despite launching with a best-in-class profile is also a good signal for increased and enhanced employee opt-in.

不，我認為唯一的補充是我們始終致力於開放取用。我們相信這對我們所服務的提供者和患者來說非常重要。因此，這也將成為我們在雇主選擇加入的目標。我們認為，儘管 Zepbound 的推出具有一流的形象，但其定價仍比競爭對手低 22%，這也是增加和增強員工選擇加入的一個良好訊號。

The next question is from Andrew Baum from Citi.

下一個問題來自花旗銀行的安德魯·鮑姆 (Andrew Baum)。

Could you talk to your scenario planning for post 2032, when the potential exists for generic semaglutide to be launched? There seems to be significant interest and investment in capacity expansion. Now obviously, this is complex, as you outlined, given not just the API but (inaudible) and IP and the rest of it. But I'm just curious how you think about that in terms of future-proofing your business against step edits and other, thinking about your broader incretin portfolio.

您能否談談您對 2032 年後的情境規劃，屆時仿製藥索馬魯肽有可能上市？人們似乎對產能擴張表現出了濃厚的興趣並進行了投資。現在顯然，正如您所概述的，這很複雜，不僅考慮到 API，還考慮到（聽不清楚）和 IP 以及其餘部分。但我只是好奇你如何看待這一點，考慮到你更廣泛的腸促胰素產品組合，以確保你的業務免受步驟編輯和其他方面的未來影響。

Thanks, Andrew. For that very long-term question, I'll pass it over to Anat to talk about 2032 and beyond.

謝謝，安德魯。對於這個非常長期的問題，我將把它交給 Anat 來討論 2032 年及以後的問題。

We do look at 2032 and we actually do look beyond. And the way we look at our business, it is a long-term business. It's not a business that changes every year or 2. So we do look at the long-term horizon both in terms of the commercial products as well as what's coming through the pipeline. And as we think through the events of that next freeze, whether for our products or those of competitors, our way of managing through that is to bring new breakthrough innovation to the marketplace.

我們確實著眼於 2032 年，而且我們確實展望了更遠的未來。我們看待我們業務的方式是，這是一項長期業務。這不是每年或兩年都會改變的業務。因此，我們確實著眼於商業產品以及正在開發的產品的長期前景。當我們思考下一次凍結的事件時，無論是我們的產品還是競爭對手的產品，我們的管理方式就是為市場帶來新的突破性創新。

So to raise the bar on our own innovation, we don't wait for that to occur or happen by competition but to bring something into the market that provides a meaningfully improved outcome for patients. So in this specific example, you use the GLPs. Certainly, tirzepatide brought in a higher bar for weight loss for patients with chronic weight management. And retatrutide that Dan referenced in his comments currently in Phase III has the potential to bring even further improved outcome for patients. So that's how we see that.

因此，為了提高我們自己的創新標準，我們不會等待這種情況發生或透過競爭發生，而是將某些東西帶入市場，為患者提供有意義的改善結果。因此，在這個特定範例中，您使用 GLP。當然，替西帕肽為長期體重管理的患者帶來了更高的減肥門檻。 Dan 在目前處於 III 期臨床試驗的評論中提到的瑞他魯肽有可能為患者帶來進一步改善的結果。這就是我們的看法。

In terms of capacity, and one of the questions is on whether companies should be or shouldn't be building, given that there is a patent expiry at the end, we do look at that and we look at the long-term horizon. But certainly, the investments in a manufacturing facility, for example, the ones we've just mentioned, whether it's in Concord, North Carolina or Research Triangle Park, between the two of them, it's about a $4 billion investment, are certainly a good investment of our capital, given that size of opportunity over the long term.

就產能而言，問題之一是公司是否應該建設，考慮到專利最終會到期，我們確實會考慮這一點，並著眼於長期前景。但當然，對製造工廠的投資，例如我們剛才提到的那些，無論是在北卡羅來納州的康科德還是在三角研究園，兩者之間大約有40億美元的投資，肯定是一個很好的投資。考慮到長期機會的規模，我們的資本投資。

I will say that as you think about potential for either generic or biosimilar entry in this space, in general, it will require quite a massive investment in capital. Just the sites that I've mentioned today on the call and we've talked about for the past year or so total about $11 billion. And that's on top of already substantial network we have around the globe, primarily in the U.S. and Europe, for production. So as you think about entering into that space, it will require some significant capital commitments.

我想說的是，當你考慮仿製藥或生物相似藥進入這一領域的潛力時，一般來說，這將需要相當大的資本投資。僅我今天在電話會議上提到的以及我們在過去一年左右討論過的網站的總價值約為 110 億美元。這是我們在全球（主要是美國和歐洲）已經擁有的龐大生產網絡的基礎上。因此，當您考慮進入該領域時，它將需要一些重大的資本承諾。

The next question is from Tim Anderson from Wolfe Research.

下一個問題來自沃爾夫研究中心的蒂姆·安德森。

So one of the competitor datasets obviously everyone is watching is the Amgen data this year. And their messaging is around longer dosing frequency, monthly dosing and then possibly a greater effect of weight loss off-therapy. So can you comment on your views of the value of extended dosing like monthly or longer? And then do you believe in that argument about efficacy being sustained off-therapy? Or is that just a function of the fact that this drug lasts longer?

因此，顯然每個人都在關注的競爭對手數據集之一是今年安進的數據。他們的訊息是圍繞更長的給藥頻率、每月給藥以及治療後可能產生更大的減肥效果。那麼您能否評論一下您對延長劑量（例如每月或更長時間）的價值的看法？那麼您是否相信治療結束後仍能維持療效的論點？或者這只是因為這種藥物的持續時間更長？

Dan?

擔？

I'll start with the second and then maybe Patrik will weigh in on potential value here, although that could be a good question for Amgen. Look, I think the sustainability data I saw in that publication are a bit underwhelming. And it's a very high-dose drug at half-life of an antibody. So just based on plasma concentrations, that would be extended to -- expected to remain there after a month or 2.

我將從第二個開始，然後帕特里克可能會權衡這裡的潛在價值，儘管這對安進來說可能是一個很好的問題。看，我認為我在該出版物中看到的可持續發展數據有點平淡無奇。它是一種抗體半衰期非常高劑量的藥物。因此，僅根據血漿濃度，該濃度將延長至 - 預計將在一兩個月後保持不變。

It doesn't surprise me. But what we're seeing is that at doses that are reasonably well tolerated, if there were any doses that are reasonably well tolerated, weight loss is lower than what we would need to see to take a molecule to Phase III for sure. And sustainability doesn't appear to be at all differentiated.

這並不令我驚訝。但我們看到的是，在耐受性相當好的劑量下，如果有任何耐受性相當好的劑量，體重減輕肯定低於我們需要看到的分子進入 III 期的情況。而且可持續性似乎根本沒有差別。

My only addition would be that when we look at the market research, of course, convenience is one factor. But it's not necessarily the most important factor when it comes to provider and consumer selecting treatment. So I'm really excited about the cores we have in our hands, of course, tirzepatide remaining a foundational treatment for obesity but also with the addition of retatrutide and orforglipron and also the opportunities here to look into options with additional non-weight loss-dependent pharmacology to complement the assets we have in the pipeline.

我唯一補充的是，當我們進行市場研究時，當然，便利性是一個因素。但在提供者和消費者選擇治療時，這不一定是最重要的因素。因此，我對我們手中的核心感到非常興奮，當然，替西帕肽仍然是肥胖症的基本治療方法，但也添加了瑞他魯肽和奧福格列隆，並且還有機會研究額外的非減肥選擇－依賴藥理學來補充我們正在開發的資產。

Thank you both. Dave, do you want to wrap this up?

謝謝你們倆。戴夫，你想結束這件事嗎？

Yes, absolutely. That's good, Joe. Thanks. We appreciate everyone participating today and, of course, your interest in the company. 2023 was a really productive year for Lilly. And we look forward to continued momentum in 2024 with a strong guide today. Thanks again for dialing in. And please follow up with Joe and the IR team if you have additional questions that weren't answered. Thanks.

是的，一點沒錯。很好，喬。謝謝。我們感謝今天參與的每個人，當然還有你們對公司的興趣。 2023 年對禮來公司來說是非常有成果的一年。我們期待在今天的強力指引下，2024 年繼續保持強勁勢頭。再次感謝您撥打電話。如果您還有其他問題未解答，請與 Joe 和 IR 團隊聯絡。謝謝。

Thank you. Ladies and gentlemen, this does conclude our conference for today. This conference will be made available for replay beginning at 1 p.m. today running through February 20 at midnight. You may access the replay system at any time by dialing (800) 332-6854 and entering the access code 187676. International dialers can call (973) 528-0005. Thank you for your participation. You may now disconnect your lines.

謝謝。女士們、先生們，我們今天的會議到此結束。該會議將於下午 1 點開始重播。今天一直持續到 2 月 20 日午夜。您可以隨時撥打 (800) 332-6854 並輸入存取代碼 187676 存取重播系統。國際撥號者可以撥打 (973) 528-0005。感謝您的參與。現在您可以斷開線路。