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，感謝你們的支持，歡迎參加禮來公司 2023 年第四季財報電話會議。 （操作員指示）現在，我想將會議交給主持人、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 Vice President of Investor Relations.

早安，謝謝你，保羅，謝謝你參加禮來公司 2023 年第四季收益和 2024 年指導電話會議。我是投資者關係資深副總裁喬·弗萊徹。

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

參加今天電話會議的還有：禮來公司董事長兼執行長 Dave Ricks； Anat Ashkenazi，財務長；禮來免疫學首席科學官兼總裁 Dan Skovronsky 博士；禮來神經科學公司總裁 Anne White；禮來國際總裁 Ilya Yuffa； Jake Van Naarden，禮來神經科學公司總裁 Anne White；禮來國際總裁 Ilya Yuffa； Jake Van Naarden，禮來神經科學公司總裁 Anne White；禮來國際總裁 Ilya Yuffa； Jake Van Naarden，禮來公司 Loxoson 總裁和禮來管理。投資者關係團隊的 Michala Irons、Mike Sprengnether 和 Lauren Zierke 也一同出席了會議。

During this conference call, we anticipate making projections and forward-looking statements based on our current expectations. Actual results could differ materially due to several factors, including those listed on Slide 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。實際結果可能因多種因素而出現重大差異，包括投影片 3 中所列的因素。有關可能導致實際結果出現重大差異的因素的其他資訊包含在我們向美國證券交易委員會提交的最新 10-K 表格以及後續 10-Q 表格和 8-K 表格中。

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

我們提供的有關我們的產品和管道的資訊是為了投資界的利益。它並非旨在用於促銷，且不足以用於規定決策。當我們轉到準備好的評論時，請注意我們的評論將集中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。我們增加了營業收入，改進了產品線，並透過合作夥伴關係和協作推進了外部創新議程。我們持續投資於公司製造基礎設施的品質、可靠性和彈性，最重要的是，為更多患者提供新的拯救生命和改變生活的藥物。

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成長勢頭，全年營收成長 20%，最近一個季度營收成長 28%。去年，我們宣布 donanemab、tirzepatide、mirikizumab 和 pirtobrutinib 的 III 期臨床試驗取得了積極的進展。我們也宣布了奧格利普龍和瑞他妥肽的 II 期臨床試驗結果呈陽性，並將這兩種重要分子推進至 III 期臨床試驗。

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計畫。最近，我們宣布了在德國建造新的高科技製造基地的計劃。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症產品組合。

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 EU 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，在過去的一年，我們為患者帶來了創新的新藥。 2023 年，我們獲得了歐盟對 Zepbound、Jaypirca、Omvoh、Ebglyss 的監管批准，以及 Verzenio 的擴展標籤和 Jardiance 的兩項新適應症的批准。這項進展將成為推動頂級營收成長和利潤率擴大的基礎。

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 these in his update.

正如您在投影片 4 中看到的，我們在第四季繼續在策略交付方面取得進展。我們的新產品銷售額成長了 20 多億美元，營收成長了 28%。自上次財報電話會議以來，我們已實現多個關鍵的管道里程碑。除了 Zepbound 和 Jaypirca CLL 批准之外，今天，我們還宣布了 tirzepatide II 期 SYNERGY-NASH 試驗以及 Verzenio III 期 CYCLONE 2 試驗的頂線結果。丹將在他的更新中詳細討論這些問題。

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，我們在第四季度完成了對 Mablink Bioscience 和 POINT Biopharma 的收購，後者擴大了我們在放射性配體療法方面的產能和能力。最後，我們宣布連續第六年增加15%的股息，並在第四季派發了超過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.

在第 5 張投影片上，您將看到自我們第三季財報電話會議以來的關鍵事件列表，其中包括幾個重要的監管、臨床和其他更新。現在我將把電話轉給 Anat 來回顧我們的第四季業績。

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。投影片 6 總結了 2023 年第四季的財務表現。我將重點評論非 GAAP 業績。我們對第四季和全年強勁的財務表現感到滿意。我們的業績亮點是營收持續加速成長，這得益於我們的新產品和成長型產品。

Q4 revenue increased 28% compared to Q4 2022. Excluding divestitures, 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，這代表著由 Mounjaro、Verzenio、Jardiance 和最近推出的 Zepbound 推動的環比收入成長加速。全年來看，受銷售 16% 強勁成長的推動，營收成長了 20%。毛利率佔收入的百分比增加至82.3%。本季毛利率受益於更高的實際價格，但被更高的製造費用部分抵消。

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%，主要原因是與推出新產品和增加適應症相關的費用增加以及激勵薪酬成本增加。研發費用增加了28%，主要原因是後期資產的開發費用增加、早期研究的額外投資以及激勵薪酬成本增加。

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.

在第四季度，我們確認了 6.23 億美元的收購智慧財產權與開發費用，這對每股收益產生了 0.62 美元的負面影響。 2022 年第四季度，收購的 IPR&D 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.

第四季營業收入成長 29%，主要得益於新產品推出帶來的收入增加，但營業費用的成長部分抵銷了這一成長。本季營業收入佔收入的百分比約為 28%，其中包括因收購智慧財產權和開發費用而產生的約 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.

我們的第四季有效稅率為 13.1%，而 2022 年第四季為 7.3%。 2023 年第四季有效稅率較高，主要是因為與 2022 年同期相比，淨離散稅收收益較低，以及波多黎各的新稅制。總體而言，我們第四季的每股盈餘為 2.49 美元，較 2022 年第四季成長 19%，其中包括收購智慧財產權和開發費用帶來的 0.62 美元的負面影響，而 2022 年第四季為 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 上，我們量化了價格、利率和數量對收入成長的影響。受 Mounjaro、Verzenio 和 Zepbound 強勁成長的推動，美國第四季營收成長了 39%。受 Mounjaro 接入和儲蓄卡動態以及回扣和折扣估算的一次性有利變化的推動，美國淨價本季上漲了 27%。除蒙扎羅以外，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.

歐洲第四季延續強勁成長趨勢。不包括因獲得歐盟批准和推出 Ebglyss 而獲得的里程碑相關的 6500 萬美元收入，收入按固定匯率計算增長了 11%，主要得益於 Verzenio、Jardiance 和 Taltz 的銷量增長。對於日本而言，我們很高興看到第四季度的強勁增長，收入按固定匯率計算增長了 15％，這主要得益於 Verzenio 和 Mounjaro 的銷量增長。

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.

移居中國。第四季營收以固定匯率計算成長 7%，銷量成長 10%，但價格下跌部分抵銷了這一成長。第四季銷售成長主要得益於達伯舒（Tyvyt）。我們很高興看到中國在 2023 年恢復成長。世界其他地區的收入按固定匯率計算下降了 10%。然而，如果排除 2022 年第四季度 Alimta 在韓國和台灣銷售權利的影響，銷售額按固定匯率計算增長了 9%，這主要得益於 Mounjaro 和 Verzenio 的銷量增長。

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 15 percentage points of volume growth for the quarter.

投影片 9 顯示了各產品類別對全球銷售成長的貢獻。如您所見，新產品和成長產品類別合計為本季的銷售成長貢獻了約 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，我想重點介紹 Verzenio，該公司第四季度全球銷售額增長了 42%，這得益於強勁的需求增長以及（在較小程度上）更高的實際價格。持續的正面動力是由早期乳癌適應症推動的，轉移性適應症表現穩定。 Jardiance 延續了 2023 年的強勁表現，本季全球營收成長了 30%。在美國，受需求成長的推動，Jardiance 的營收成長了 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%。由於銷量下降和實際價格下降，美國收入下降了 18%。我們在履行 Trulicity 訂單時遇到了間歇性延遲。從 12 月初開始一直到今年 1 月，FDA 藥品短缺網站上均顯示所有劑量的 Trulicity 供應有限。我們預計未來幾個月內某些劑量的訂單履行可能會出現間歇性延遲。在國際市場上，Trulicity 的銷售持續受到我們採取措施的影響，以盡量減少對現有患者的潛在幹擾，包括與醫療專業人員溝通不要讓新患者使用 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.

移至投影片 11。隨著越來越多的第 2 型糖尿病患者受益於該藥物，Mounjaro 繼續保持強勁成長。第四季全球營收從 2023 年第三季的 14 億美元成長至 22 億美元以上。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，這得益於對回扣和折扣估算的一次性變更。經過這項一次性變更的調整，美國第四季的連續淨銷售額將成長約 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.

自上次呼籲以來，我們進一步擴大了患者進入蒙扎羅的機會。截至 2 月 1 日，美國 2 型糖尿病患者在商業和 D 部分計劃中的總體可及性為 90%，其中商業患者的可及性為 92%。這次擴大使用範圍使得 Mounjaro 幾乎與現有的注射用腸促胰島素處於同等水平，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 美元的非承保共同支付卡計劃於 6 月 30 日到期，我們現在認為所有處方均已付款。與 2022 年第四季相比，2023 年第四季的 Mounjaro 淨價受益於美國共同支付卡計畫的這項變更。回想一下，在 2022 年底對非承保共同支付計劃進行更改後，已經開始使用 25 美元共同支付卡的患者可以繼續使用該計劃直到 6 月 30 日。今天，沒有保險的商業保險患者使用當前的非承保共同支付計劃，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.

翻到第 12 張投影片。 11 月，我們獲得了 FDA 批准，可以使用 Zepbound 治療肥胖症成人或超重且患有體重相關合併症的成年人。我們隨後於 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集訪問。我們很高興看到，截至 2 月 1 日，大約有 1/3 的商業壽命已被早期覆蓋。

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.

進入這個市場將會更加漸進，因為個體雇主需要在典型的處方集簽約之後選擇加入保險。我們專注於建立處方集訪問和雇主選擇加入。但我們預計，實現該市場的廣泛開放還需要一段時間。同時，對於尚未投保的人來說，美國藥局也可以享受我們計劃的商業優惠。

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 Part D中，減肥藥物仍然被禁止報銷。在第四季度，我們確認 Zepbound 的銷售額為 1.76 億美元，其中約 3/4 來自初始通路備貨。我們看到的初步處方趨勢令人鼓舞。

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 donanemab and lebrikizumab, all of which we expect to serve as drivers for continued growth through the balance of the decade.

在第 13 張投影片上，我們提供了有關資本配置的最新資訊。展望 2024 年及以後，我們對現有的商業組合充滿信心，並得益於最近推出的 Mounjaro、Jaypirca、Omvoh 和 Zepbound 以及可能推出的 donanemab 和 lebrikizumab，我們預計所有這些都將成為未來十年持續增長的動力。

On Slide 14, you'll see a summary of our outlook that outlines 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.

在第 14 張投影片上，您將看到我們的展望摘要，其中概述了我們為實現策略成果所做的資本部署決策。我們將透過研發、業務發展和全面的製造擴張計劃投資於我們現有的產品組合和未來的創新，旨在推動收入成長並加快向患者提供改變生活的藥物。我們將繼續透過與獲利成長同步的股利增加以及以過剩資本回購股票的方式向股東返還資本。

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。我們重點介紹一些可能影響我們 2024 年財務表現的動態。我們預計，受近期推出的產品的積極勢頭推動，核心業務收入（不包括資產剝離收入）將繼續保持強勁增長，預計將增長近 30%，達到我們預期範圍的中位數。

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.

在腸促胰島素領域，預計成長將由 Mounjaro 和 Zepbound 引領。 2023 年，我們在擴大蒙扎羅的通道方面取得了巨大進步。進入 2024 年，90% 的商業和 D 部分人壽保險已得到保障。 Zepbound 的報導在 12 月初推出後取得了良好的開端。我們預計這兩個 tirzepatide 品牌都將為禮來公司 2024 年的收入成長做出巨大貢獻。

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 銷售疲軟趨勢的持續所部分抵消。 Trulicity 在美國近期收入的下降是因為供應緊張造成的。我們在美國境外的行動也對交易量產生了影響。

As for supply outlook for incretins, our manufacturing organization continues to execute well on the most ambitious expansion agenda in our company's long history. Given strong demand and the 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.

至於腸促胰島素的供應前景，我們的製造組織繼續出色地執行公司悠久歷史上最雄心勃勃的擴張計劃。鑑於強勁的需求以及產能完全上線所需的時間，我們仍然預計 2024 年的需求將超過供應。 2022 年末，我們曾預計，到 2023 年底，我們的腸促胰島素自動注射筆的產能將翻倍。這一目標的實現離不開我們全球製造業同事和合作夥伴的巨大努力。

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 presentations like our multi-use KwikPen, which received regulatory approval in the U.K. in late January. We expect our perenteral 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.

2024 年，我們將以同樣的緊迫感繼續擴大產能，不僅透過增加自動注射器的產能來實現，還將透過替代產品來實現，例如我們的多用途 KwikPen，該產品於 1 月底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腸外生產基地最快將於 2024 年底投入生產，產品將於 2025 年出貨。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，我將提供更多關於我們 2024 年腸促胰島素供應計劃的時間和速度的背景資訊。雖然我們每季都在繼續擴大供應，但我們預計最顯著的產量成長將出現在下半年。我們預計，2024 年下半年可銷售劑量的產量將至少是 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 incretins, we look forward to progressing our launch trajectory for two other Lilly medicines approved and launched in 2023, Jaypirca and Omvoh.

請注意，雖然去年我們的評論重點關注與 2022 年相比的自動注射器設備的容量，但現在我們指的是生產的可銷售劑量，這與患者和投資者更相關。除了腸促胰島素之外，我們還期待著推進禮來公司另外兩種將於 2023 年獲批並上市的藥物 Jaypirca 和 Omvoh 的上市進程。

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 robust Phase III program continues.

Jaypirca 最初於 2023 年 1 月根據加速審批計劃獲得 FDA 批准，用於治療復發或難治性套細胞淋巴瘤成年患者，並於 2023 年 12 月根據加速審批計劃獲得 FDA 批准，用於治療已接受過至少兩種先前療法的 CLL 或 SLL 成年患者。隨著我們強大的 III 期計劃的繼續，我們期待有機會繼續利用這種藥物來幫助患者。

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 option 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，並於同年早些時候在日本、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。 2024 年，我們期待美國再推出兩種藥物，donanemab 和 lebrikizumab。

We continue to expect FDA regulatory actions on donanemab in [Q1 2024] (corrected by company after the call) 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.

我們繼續預計 FDA 將在 [2024 年第一季] 對 donanemab 採取監管行動（公司在電話會議後進行了更正），並仍然對 donanemab 造福阿茲海默症患者的巨大潛力充滿信心。鑑於目前診斷和治療的準備情況，初期的採用將受到一定限制。我們預計，一旦獲得批准，donanemab 對 2024 年的成長貢獻將很小。

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 approval of lebrikizumab by the end of the year.

Lebrikizumab 去年由我們的合作夥伴 Almirall 在歐洲獲得批准並以 Ebglyss 品牌名稱上市，並於 1 月在日本獲得監管部門的批准。至於美國，我們期待lebrikizumab在今年年底前獲得批准。

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 的療效、安全性和劑量可以使其成為治療中度至重度異位性皮膚炎的龐大且不斷增長的市場中患者和處方醫生的有吸引力的選擇。考慮到 FDA 監管行動的預期時間，我們預期 lebrikizumab 對 2024 年營收成長的貢獻僅為適度。

Beyond our recently launched portfolio of medicines, 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 Verzenio 將在早期乳癌適應症的推動下繼續增長，我們臨床數據的數量和成熟度強化了它作為淋巴結陽性、高風險早期乳癌的標準治療方法的地位。 Jardiance 是另一個對成長做出突出貢獻的公司。我們預計 2024 年營收將繼續成長，但速度將會放緩，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，我們預計各主要地區都將加速成長，這不僅是由於預期推出的 tirzepatide，而且也得益於 Verzenio、Jardiance 和 Taltz 的持續強勁成長。最後，我們尋求創造未來十年的長期價值。我們將繼續對我們的價值鏈進行投資，包括近期和即將推出的潛在產品、我們的產品線以及我們的製造足跡。

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，預計營收在 404 億美元至 416 億美元之間。以 2024 年範圍的中點計算，這代表我們的核心業務成長約 20% 或 29%，其中不包括 2023 年資產剝離的影響。

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.

就我們 2024 年全年營收成長的階段而言，雖然我們沒有提供季度指導，但我們預計下半年營收成長將加速，這與腸促胰島素劑量供應的增加相一致。就我們核心業務（不包括資產剝離）的定價而言，我們預計 2024 年價格將出現高個位數百分比下降。 Mounjaro 非覆蓋共同支付卡動態的持續基期影響將抑制 2024 年上半年的價格下跌，預計下半年價格將出現更顯著的下跌。

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精簡的方法。我們沒有提供毛利率、研發成本以及行銷、銷售和管理成本三個單獨的指導項目，而是提出了一個代表計劃成本後的利潤率的新比率，該比率通過從毛利率中減去研發成本以及營銷、銷售和管理成本，然後將該數字除以收入來計算。我們將該比率表示為百分比。到 2024 年，我們預計非 GAAP 基礎上的成長率將在 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，但我們的預期仍然是，由於生產率的提高和產量被價格壓力和新製造設施的成本所抵消，我們將在非 GAAP 基礎上維持約 80% 的毛利率。

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

至於我們主要類別的費用成長，我們預計行銷、銷售和管理費用將在 2024 年再次成長，儘管成長速度低於收入，但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，這得益於我們為未來進行的投資，即我們所有研發階段的投資都會不斷增加，而大部分的資金增長將受到正在進行的和新的後期階段機會的推動。我們預期研發費用的成長速度將高於行銷、銷售和管理費用的成長速度。其他收入和支出預計在 4 億美元至 5 億美元之間，主要由於利息支出增加。

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.

談到稅收。我們預計 2024 年非 GAAP 有效稅率約為 14%。請注意，該稅率並不假設推遲或廢除《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規定。如果這項變更生效，我們 2024 年的有效稅率將會適度提高。

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，我們在 2024 年指引中不包括任何潛在或待定的已收購 IPR&D 和開發里程碑費用。隨著所獲得的智慧財產權與開發 (IPR&D) 和開發里程碑費用的產生，我們將每季提供關於智慧財產權與開發 (IPR&D) 對每股盈餘影響的最新資訊。為了指導模型的目的，我們目前估計 2024 年的稀釋加權平均流通股數約為 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 approaching 30% and continued investment to drive future growth. Our outlook for top-tier revenue growth and operating margin expansion remains on track.

我們將以強勁的勢頭邁入 2024 年，並擁有絕佳的機會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，這要歸功於我們核心業務預計收入成長接近 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確。

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

現在我將電話轉給丹，重點介紹我們在研發方面取得的持續進展。

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。我首先要介紹的是我們在對抗糖尿病、肥胖及其併發症方面的進展。今天，我們宣布了 SYNERGY-NASH 的積極結果，這是一項針對經活檢證實的代謝功能障礙相關脂肪性肝炎（也稱為 MASH）成人患者的 tirzepatide 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，該研究達到了其主要終點，高達 74% 的參與者在 52 週時達到 MASH 消失且纖維化未惡化，而使用安慰劑的參與者中只有不到 13% 達到這一終點。我們同樣對次要終點的結果感到鼓舞，即評估纖維化的改善。

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.

雖然該研究並非旨在以統計學方式評估纖維化的改善情況，但研究結果顯示，所有劑量均具有臨床意義的治療效果，與安慰劑相比，有相當一部分參與者的纖維化階段至少降低了一個，且 MASH 沒有惡化。這些不良事件與其他研究肥胖症或 2 型糖尿病患者使用 tirzepatide 的臨床試驗中觀察到的不良事件一致。 SYNERGY-NASH 的完整結果將於今年稍後在醫學大會上公佈。

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 獲得了 FDA 批准，這是禮來公司首個核准的肥胖症治療方法。這對患者和該領域來說都是一個里程碑，因為 Zepbound 是第一個也是唯一一個核准的活化兩種腸促胰島素受體 GIP 和 GLP-1 來解決體重過重根本原因的治療方法。

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，我們用於治療糖尿病的葡萄糖敏感胰島素受體激動劑現已進入第一階段，用於治療心臟衰竭的長效心房利鈉肽也已進入第一階段。

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 推進至肥胖症治療的第二階段，並已開始為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製藥公司報告了馬度肽治療中國成年肥胖症的 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，而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，Verzenio 與阿比特龍聯合使用未能達到改善轉移性去勢抵抗性前列腺癌男性的放射學無進展生存期的主要終點。在研究中，我們採用了自適應的 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.

儘管第二階段的研究達到了獨立資料監測委員會建議啟動第三階段研究的預定閾值，但該訊號並未在第三階段研究的更大樣本量中得到證實。整體安全性和耐受性概況與已知的藥物概況一致。我們期待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.

自從我們上次收益電話會議以來，Jaypirca 已獲得 FDA 加速審批計畫的批准，用於治療已接受過至少兩種療法（包括 BTK 抑制劑和 BCL-2 抑制劑）的 CLL 或 SLL 成年患者。我們還報告稱，旨在將此批准轉換為傳統批准的 III 期確認試驗（稱為 BRUIN CLL-321）已達到其主要終點。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獲得 FDA 批准的非共價 BTK 抑制劑，可以擴大針對 BTK 通路的益處，使先前接受共價 BTK 抑制劑和 BCL-2 抑制劑治療的 CLL 和 SLL 患者受益。這是 Jaypirca 在 2023 年第二次獲得批准，第一次是針對 MCL 患者。我們相信這兩項適應症僅代表 Jaypirca 最終對患者產生的影響的開始。我們期待看到 CLL、SLL 和 MCL 的其餘 III 期計劃的數據。

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.

在第四季度，我們完成了對 POINT Biopharma 的收購，這標誌著禮來公司開始進軍放射性配體治療領域，這是一項前景光明的技術，有可能為一系列癌症的治療帶來有意義的進展。我們歡迎新的 POINT 同事加入禮來公司，並期待在他們的工作基礎上進一步提升禮來公司的這項能力。

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 nectin-4 and one against folate receptor alpha; and an actinium-PSMA radioligand therapy.

2024 年也將成為腫瘤學新臨床起步特別有成效的一年，因為我們開始看到在收購 Loxo 後約 4 年前實施的新腫瘤學研發策略的成果。透過內部發現努力和業務開發相結合，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；兩種具有拓撲異構酶有效載荷的抗體-藥物偶聯物，一種針對 nectin-4，一種針對葉酸受體 α；以及錒-PSMA-PSMA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.

我稍後會談談我們的臨床 KRAS G12C 項目，但您可以看到，我們正在付出真正的努力來開發一套針對 RAS 的治療方法。我們很高興看到這些探索努力迄今已產生三種潛在藥物。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產品組合持樂觀態度，並且我們確實已經實現了產品線中治療方式的多樣化。

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，我們很高興看到我們的 KRAS G12C 抑制劑 olomorasib 已進入 II 期臨床試驗，我們正在 Optimus 計畫下完成 III 期臨床試驗的劑量選擇，該計畫於今年稍後啟動。現在您可以在 clinicaltrials.gov 上看到該研究的完整設計。

By way of reminder, we started this program years 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比競爭對手晚了好幾年，透過對這個在我們看來很棒的分子的集中努力，我們彌補了大部分的時間。我們相信，我們現在與我們最接近的競爭對手不相上下，我們希望證明我們的藥物能夠與 PD-1 更好地結合。最後，在腫瘤學領域，我們終止了 RET 抑制劑 2 的開發，因為它不符合我們進行內部開發的門檻。

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，我們將兩項新資產轉移到第一階段，並將用於治療牛皮癬的 Kv1.3 拮抗劑推進到第二階段。 Lebrikizumab 在歐盟以 Ebglyss 品牌名獲準用於治療異位性皮膚炎，該藥物由我們的合作夥伴 Almirall 在歐盟銷售。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，今年 1 月，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，結果表明，第一位參與者（一位患有十多年嚴重聽力損失的個體）在單次給藥後 30 天內聽力恢復。手術治療和研究治療耐受性良好，未報告嚴重不良事件。

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醫療保健問題並改善個別患者的生活。現在，我們在管道圖上顯示了處於第二階段的 OTOF 基因療法，因為我們已經開始在研究的第二階段部分招募年輕患者。

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 noted the key updates on each of these slides in my therapeutic area comments.

在投影片 18 上，我們重點介紹了自上次收益電話會議以來我們精選的管線資產的更新情況，投影片 19 總結了我們 2023 年的關鍵事件。我在治療領域評論中記錄了每張投影片上的關鍵更新。

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.

翻到第 20 張投影片。我們想強調一下 2024 年可能發生的關鍵事件。如您所見，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促胰島素產品的 III 期開發項目，包括我們的口服藥物奧格列酮和新型每週注射三重受體激動劑瑞他曲肽。這些項目正在進展中，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，我們計劃啟動瑞他曲肽針對第 2 型糖尿病的 III 期臨床試驗，以補充正在進行的肥胖症及相關併發症試驗。此外，今年我們也計劃啟動 lepodisiran（一種用於治療心血管疾病的降低 LPA 的 siRNA 療法）的 III 期臨床試驗。

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 tirzepatide，我們期待今年能獲得一些額外的關鍵數據。除了 SYNERGY-NASH 之外，我們預計今年還將看到 III 期阻塞性睡眠呼吸中止症和 III 期心臟衰竭研究的結果。我們注意到投資者對 SURPASS-CVOT 時機的興趣日益濃厚。我們可以重申，儘管 clinicaltrials.gov 上有列表，但我們預計 2025 年的數據將很快更新，以反映我們基於事件發生率的當前假設。

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，這是我們在肥胖患者中對 tirzepatide 與高劑量 semaglutide 進行頭對頭研究。我們也預計今年稍後將公佈每週基礎胰島素胰島素 efsitora alfa 的完整 III 期計畫讀數。

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 donanemab 可能在今年第一季上市。我們正在推進全球範圍內的監管審查。我們現在已經推出了基於 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機構合作，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在克隆氏症治療中取得積極的III期數據後，我們計劃今年向FDA提交該適應症的申請。此外，根據美國 FDA 對 lebrikizumab 的完整回覆函，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，我們期待在今年稍後將我們的 KRAS G12C 抑制劑 olomorasib 在第二階段劑量選擇之後推向第三階段。最後，我們期待看到我們的免疫抑制劑 III 期研究 EMBER-3 對轉移性乳癌患者進行單一療法和與 Verzenio 聯合療法治療的結果。

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一年。我們預計 2024 年將會有更多類似的進展，因為我們在推動產品線以造福患者方面取得了有意義的進展。現在我將把電話轉回給戴夫，請他作最後發言。

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，丹，恭喜你和 LRL 團隊度過了豐碩的一年。在進入問答環節之前，讓我簡單總結一下我們在第四季的進展。

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持續獲得發展勢頭，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重大進展。我們將繼續投資於近期和即將推出的產品、後期藥物、早期能力和業務發展，所有這些都將為未來的成長奠定基礎。第四季度，我們完成了 POINT Biopharma 的收購，並宣布了在德國建立新生產基地的計畫。我們透過股利向股東返還了超過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，我們在一月份宣布，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展、現代化和改進。我要感謝她多年來為禮來公司所做的傑出貢獻。

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

現在我將把電話交給喬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 Anat's 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。在深入問答之前，我想澄清一點。當 Anat 就 donanemab 監管行動時機發表準備好的演講時，我們可能聽到了一些低沉的聲音。正如丹所提到的，預計時間是今年 2024 年第一季度，收到一些記錄說有一些低沉的聲音，所以只是想澄清一下這個重要點。

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.

現在進入問答環節，我們希望盡可能回答來電者的問題，並及時結束通話。因此與前幾季一致，我們將對每個來電者回答一個問題，因此請您將每個來電者限制為一個問題，因為我們將在上午 11:15 結束通話。 （操作員指示）保羅，請提供問答的說明，我們已經準備好迎接第一位呼叫者了。

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

（操作員指示）今天的第一個問題來自摩根士丹利的 Terrence Flynn。

Congrats on the progress. Just wondering for your GLP franchise, ex U.S., you under-index 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?

恭喜你取得進展。只是想知道，對於您的 GLP 特許經營權（不包括美國），您的指數是否低於您的主要競爭對手。我只是想知道，當我們考慮 2024 年以及 2025 年的成長時，縮小這一差距會面臨哪些障礙？

Thanks, Terrence, 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。我將這個問題交給禮來國際總裁伊利亞‧尤法 (Ilya Yuffa) 來回答。

Thanks, Terrence. 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。當我們考慮在美國以外推出 Mounjaro 時，我們已經在多個精選市場推出了該產品。我們在許多市場上都有競爭基礎。我們預計還會繼續推出新產品。我們剛剛在美國以外的特定市場推出了小瓶裝產品，主要是澳洲、加拿大、德國和波蘭。

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，因此我們期待在那裡推出該產品。隨著我們獲得多用途 KwikPen 的更多監管批准，並且我們監控供應能力的提升，我們將全年繼續在其他市場推出該產品。因此，我們預計 Mounjaro 將在美國以外地區推出，並在今年全年以及 2025 年繼續成長。

The next question is coming from Chris Schott from JPMorgan.

下一個問題來自摩根大通的 Chris Schott。

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，似乎您在覆蓋範圍方面取得了很大進展。但我們只是對今年剩餘時間的預期感興趣，因為我們考慮的是報告的範圍以及如何考慮 ASP。我想，核心問題是，認為大多數支付 Wegovy 費用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。我將把關於 Zepbound 覆蓋範圍的問題交給 Patrik 來評論。

Yes, thank you very much, Chris. As we stated, we are pleased with where we are so early in launch with 35% commercial access. 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，克里斯。正如我們所說的，我們對如此早期的發布以及 35% 的商業訪問率感到非常滿意。我們未來的努力實際上將是繼續擴大付款人的訪問權限。但我們不僅會像對待 Mounjaro 一樣採取非常嚴謹的方式來做到這一點，而且還會確保獲得雇主的選擇。正如阿納特在準備好的發言中提到的那樣，這需要一些時間。但我們假設，以我們目前的訪問量，我們的訪問量將與競爭對手提到的一致，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，沒有一個可靠的雇主選擇加入來源。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收益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存取權限。我認為我們對迄今為止從市場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美術館的 Seamus Fernandez。

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得到一些啟發。您是否看到了 SYNERGY-NASH 獲得加速批准的前景？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並不具有統計意義？

Thanks, Seamus, for the question. Dan?

謝謝 Seamus 提出這個問題。擔？

Yes. Thanks, Seamus. This data 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，西莫斯。這些數據對我們來說確實很新，但我們對此感到非常興奮。我們還沒有機會與 FDA 討論下一步的措施，但我們期待有這樣的機會。當然，這是一項約有 190 名參與者的小規模試驗，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，我想我可能之前曾說過，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。但看到這些數據具有纖維化在臨床上有意義的改善，我感到非常興奮。

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解釋退出情況，特別是安慰劑組的情況。因此我們必須等待科學報告才能看到所有的 p 值。但我們對整個資料包非常樂觀，這對患者來說意味著什麼，無論是在阻止 MASH 進展還是逆轉纖維化方面。

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，當您考慮在各個地點進行製造擴建時，這顯然對所有現有的 GLP 需求都非常重要，我很好奇，您如何平衡美元投資與您對 orforglipron 的臨床和商業概率，特別是在所有盲法數據湧入的情況下？

Thanks, Umer. Dave?

謝謝，烏默爾。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，隨著我們進入腸促胰島素真正強勁的成長階段，我們非常注重資本配置。但當務之急是創造新的產能。目前，限制因素對我們來說並不是真正的財務因素，因此您可以期待我們全力投資。我們不會因為現金流或其他原因而放慢腳步。這實際上取決於人員和供應商的技術能力，才能使設施上線。在腸外治療方面尤其如此。

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風險建設。我認為，考慮到我們內部評估的可能性以及積極的第三階段的另一面的機會，我們認為這是一項明智的投資。正如我們之前所評論的那樣，正如您所知，它依賴於禮來公司內部和外部非常不同的資產。所以這裡有有機化學、API、藥片和膠囊，所以設定非常不同。

So 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 a bet worth taking.

因此，我們將其與我們強勁的注入式投資相結合。如果我們錯了，好吧，如果 orforglipron 不是一款強大的產品，我們最終將不得不接受它。但如果確實如此，我認為它確實開始改變這個類別的供應數學。我認為這是一個值得冒的風險。

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

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

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?

關於 SURPASS-CVOT，您提到它推遲到 2025 年。我認為這意味著唯一的中期展望已經過去了。然後你要評估非劣效性和優越性。您是否同意，您真正需要在這裡展示的是優越性，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?

提姆，謝謝你提出這幾個問題。也許我們可以派出臨時人員來演練，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 is not, I think, germane at all to the question on the timing on clinicaltrials.gov, which was before and continues to be the time point at which we'll have final data.

是的，當然。好吧，謝謝你的提問，提姆。如您所知，禮來公司不對中期業績發表評論。可能我們投資組合中的大多數試驗確實都有進行中期觀察的機會。但我認為這與 clinicaltrials.gov 上的時間問題完全無關，後者是在我們獲得最終數據之前並將繼續成為最終數據的時間點。

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 上設定這個時間點時，那是在 2020 年初，我們還沒有開始招募試驗，所以這是基於我們對招募率的假設，但可能更重要的是基於事件發生率的假設。隨著試驗的成熟，我們會對事件發生率有大致的了解。

So I know it's frustrating for investors and for us perhaps to wait 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.

所以我知道對於投資者和我們來說，等待更長的時間才能獲得活動是令人沮喪的。但當然，當事件發生率較低時，這對患者來說是個好消息，請記住，這是一項與藥物 Trulicity 的頭對頭試驗，我們已經知道該藥物可以有效預防 MACE 事件。

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?

恭喜你取得進展。我對您的睡眠呼吸中止症研究有一個疑問。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？您是否認為該試驗規模足夠大，足以尋求睡眠呼吸中止症的標籤？

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

謝謝 Mohit 提出這個問題。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.

是的，謝謝。對於睡眠呼吸中止症的臨床意義，實際上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數。當然，我認為這類藥物具有很大的改善這種狀況的潛力。

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 tirzepatide 的效果。可能除了我們所尋求的 AHI 的絕對百分比改善之外，我還希望看到患者從一個類別轉變，例如從中度疾病轉變為輕度疾病或類似的情況。因此，我們將研究許多因素來評估其臨床意義，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.

我想問您如何看待 GLP-1 的下游機會，例如 tirzepatide，可能用於 NASH，以及您正在追求的其他一些適應症。

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，帕特里克，你想談談嗎？

Thank you very much. I think there are two important aspects. The first one is when we refer to employer opt-in, I think employers 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, and other 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，我認為雇主確實在積極考慮列出抗肥胖藥物的好處。無論我們在心血管領域、OSA 或 NASH 以及其他適應症中產生什麼數據，對於增加雇主選擇率都極為重要。

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 Medicare D 部分患者能否獲得治療至關重要。因此，這些才是這些適應症的真正關鍵驅動因素。

The next question is coming from Kerry Holford from Berenberg.

下一個問題來自貝倫貝格的 Kerry Holford。

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 tirzepatide 肥胖症的。我很想知道為什麼您決定不在美國以外推出 Zepbound 品牌，而是尋求為 Mounjaro 尋求減肥品牌擴展。這是否與簡單性有關，或許與更快的報銷訪問有關？我想知道您是否預見到前美國政府最終傾向於將糖尿病和肥胖症預算分開的風險。

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。我會把時間交給 Ilya 來談論 tirzepatide OUS 的品牌推廣。

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，對於美國以外的更廣泛的 tirzepatide 來說，它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，無論是針對第 2 型糖尿病還是慢性體重管理，這在報銷談判方面都不會成為挑戰。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實現商業化的能力感到樂觀。

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?

戴夫，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獲取供應商和禮來藥物的平台？或者是否存在一種可以隨著時間推移而發揮作用的貨幣化模式或市場差異化？

I can start, Patrik, jump in. Yes, thanks for the question. The idea was really actually born 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 in 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.

我可以開始了，派崔克，插話。是的，謝謝你的提問。這個想法其實源自於美國患者在就診時每天面臨的挑戰。您會知道，我們的平台上有醫生查找工具以及針對偏頭痛、糖尿病和肥胖症的遠距醫療合作夥伴。在藥局裡尋找藥品是一個挑戰。我認為，尤其是在藥品供應緊張的情況下，許多患者表示他們必須開車去五、六、七家藥局才能找到他們需要的藥品。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，關於非法藥物、Zepbound 或其他減肥藥的仿製品或複合版本的傳聞很多。這令我們擔憂。我認為這與患者有關。因此，透過與 LillyDirect 合作，他們對供應充滿信心。最後，在藥局櫃檯實施我們的儲蓄計畫也是一個挑戰。而這在 LillyDirect 上 100% 都是如此。

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.

我們還沒有想過將其作為創建某種新的零售分銷業務的方式。這是為需要我們藥物的患者提供更好服務的一種方式。這就是我們現在所處的狀況。在早期，我們試圖開發它，使它更加流暢、更好，隨著時間的推移包含更多的產品，並擁有關於醫生和遠距醫療提供者的更好的資訊。因此，請關注那裡的更多發展。但到目前為止，開局良好，患者群體表現出了很大的活力和熱情。

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.

祝賀今天的更新。所以我的問題是針對戴夫和丹關於使用腸促胰島素導致的肌肉損失的問題。您能否幫助我們了解禮來公司對這場爭論的看法，並對 tirzepatide 相對於 semaglutide 的最新數據進行評論？我觀察到的是，SURMOUNT-1 顯示 3:1 的瘦肌肉損失率，而 sema 的 STEP-1 試驗顯示 1.5:1，儘管評估結果略有不同。

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

謝謝，戴夫。我會讓丹來處理這件事。

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。也許只是從我們對瘦肉和脂肪品質的看法開始，我認為瘦肉和脂肪品質的比例是一個需要考慮的重要問題。身體組成（不僅僅是體重）對患者來說很重要。例如，對於第 2 型糖尿病或心血管疾病的風險而言，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，對於使用 tirzepatide 的患者來說，該比例似乎有所改善。正如你所指出的，他們失去的脂肪質量遠遠超過瘦體重。因此，在我們進行的每一次試驗中，在試驗結束時，如果我們測量身體成分，就會發現瘦肉與脂肪的比例比試驗開始時更高。因此，我們認為身體組成的這種變化是一種益處，也是 tirzepatide 的一種潛在益處，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 or 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，這也是我們希望進一步擴展的福利。您已經看到我們努力提高身體總減重量。我們也在努力改善或進一步改善身體質量組成的變化。這就是為什麼我們收購 Versanis 並試驗比麥單抗等藥物的原因。

The numbers 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 agonism here in addition to GLP-1 agonism. That's probably the way I would interpret this data.

在我看來，您從 tirzepatide 和 semaglutide 研究中引用的數字是正確的。當然，它們並不是面對面的研究。但它確實提出了一個問題，即除了 GLP-1 激動作用之外，GIP 激動作用是否還有潛在益處。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.

我很想聽聽您對口服 GLP-1 機會的看法。我們從競爭對手那裡看到了一些混合數據。我只是想知道，根據您對 orforglipron 的投資背景，您如何看待這一發展。

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

謝謝埃文提出這個問題。派崔克，你能談談我們對口服藥物的看法嗎？

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。當我們看到肥胖問題帶來的機會時，美國有超過 1.1 億肥胖患者，全球有 6.5 億肥胖患者。我認為，考慮到目前各個市場的供應限制，注射劑不可能涵蓋所有市場。所以我認為這對 orforglipron 來說是一個很大的機會。

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.

就我們目前在第二階段所看到的情況而言，如果我們能夠在第三階段複製這些數據，那麼我們就有了一種口服藥物，其減肥效果與最具競爭力的腸促胰島素相差無幾，不是達到 tirzepatide 的水平，而是達到市場上最好的腸促胰島素的水平，並且不受食物或水的限制。因此，我們確實看到了透過 orforglipron 惠及全球患者的機會。

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.

另外還有另一個組件。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。所以這是 orforglipron 的另一個機會。因此，我們相信，這是我們在慢性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 tirzepatide 治療 NASH 的 III 期試驗可能有幾個原因。首先，禮來公司相信擁有更好的分子。其次，第二階段的數據有些不太理想。或第三種情況，禮來公司將進行第三階段研究，但尚未最終確定計畫。

But that really can't be it. 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?

但事實不可能如此。打個比方，您開始使用 LPA 進行第三階段研究，甚至沒有告訴我們第二階段研究的結果呈現陽性。那麼，關於 tirzepatide 在 NASH 中的作用，我們能得到什麼最佳結論呢？

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.

謝謝史蒂夫的精彩分析。因此首先，我應該說我們剛剛獲得了第二階段的數據，因此請給我們一個機會來確定下一步的計劃，以便可能至少推翻這裡的一個假設。數據中沒有任何不好的東西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，我們可能在瑞他妥肽中做到了。當然，我們這裡沒有瑞他妥肽的那種 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，我認為在這裡進行的 II 期試驗是積極的，並且獲得了有關 NASH 的真正有意義的數據，這迫使我們思考下一步的行動。正如我所說，這將與 FDA 進行交談。

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，在規劃任何 NASH 藥物的 III 期臨床試驗時，我們真正需要優先考慮的是盡可能地擺脫肝臟活檢，並用非侵入性檢測來代替。我認為我們和該領域的其他人已經取得了很大進展。我們看到這裡與其他疾病領域的相似之處。我們希望，未來能夠不依賴活檢進行 III 期 NASH 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.

這將對快速進行這些試驗的可行性以及 NASH 藥物的臨床應用產生深遠的影響，在這些藥物中，這些非侵入性生物標記可用於識別需要治療的患者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?

在糖尿病和肥胖者中使用 GLP-1 的持續時間，之前，您曾將糖尿病的持續時間定性為 15 個月左右，並評論說您認為我們沒有足夠的經驗。有任何更新嗎？您認為我們什麼時候才能擁有足夠的經驗，至少在初期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，你想評論一下治療持續時間嗎？

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，克里斯。我認為你是對的。這很有挑戰性。 Mounjaro 和 Zepbound 都還處於早期階段。我們在供應方面以及共同支付計劃的變化方面面臨一些特定的動態。然而，當我們查看蒙扎羅的最新數據時，這是令人鼓舞的。這表明，從 2023 年第一季開始接受治療的患者的療效至少與其他注射腸促胰島素的療效相當。

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 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，這絕對為時過早。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，影響供給、宏觀經濟和微觀經濟的因素很多。但我們確信，肥胖症的治療也需要一個最終的治療持續時間，因為即使是對於心臟衰竭和 2 型糖尿病，超過 12 個月的治療堅持期也被認為是很長的。

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。有了 Zepbound，根據我們在其他慢性疾病中看到的情況，我們肯定會看到持續時間的結束。但我們相信這些功能本身會激勵患者。

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?

摩根大通的戴維，您對 orforglipron 發表了有趣的評論，您提到該分子有很多需要證明的地方。能詳細說明一下這是什麼意思嗎？您對 orfo 的 DDI 概況有何信心？它似乎有一點 CYP3A4 抑制。那麼，鑑於您之前的一些研究將 SGLT2 排除在外，這種藥物是否能夠與 SGLT2 一起服用？

I could frame 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.

我可以解釋一下我為什麼這麼說，但也許丹可以談談特定的 DDI 問題和 SGLT2 共同給藥問題。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有一點經驗主義。當然，隨著我們每天讓更多的患者接觸這種藥物並且增加劑量，我們不會宣布這種藥物有問題，這是一個好日子。

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.

到了某個時候，我們會變得非常有自信。我們只是還沒到達那個地步。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。我們也曾在這堂課中看過其他人的表演。但我心裡沒有什麼特別的想法。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 are being dosed with orforglipron as well as other drugs like SGLT2s.

是的。謝謝，戴夫。當然，這只是正常的第三階段類型的風險，新的安全訊號總是可能出現的。我認為就 DDI 和與 SGLT2 的共同給藥而言，我們預計這是可能的。目前，我們正在進行第三階段試驗。有些患者正在服用奧格列酮以及 SGLT2 等其他藥物。

The next question is from Trung Huynh from UBS.

下一個問題來自瑞銀的 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?

鑑於昨天競爭對手提供的數據表明，GIP 對血壓和脂質變化等方面的影響較為有限，我能否問一下您對 GIP 激動作用與拮抗作用的看法？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才是前進的方向？

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-1 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。現在，我們已從數萬名參與 tirzepatide 隨機臨床試驗的參與者那裡獲得了大量有關 GIP 激動劑益處的數據。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，我們還試驗了不含任何 GLP-1 的純 GIP-1 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.

我們在此將其與最近發表的一項小型 I 期研究進行對比，該研究針對一種同時具有 GLP-1 激動作用和 GIP 拮抗作用的藥物。我在該出版物中指出，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下才會開始拮抗 GIP。這可能是該公司要問的問題。

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.

但我在臨床試驗中註意到，高劑量實際上會導致遊離脂肪酸增加，而三酸甘油酯的減少則完全減弱。這些是我們認為 GIP 產生的一些影響。因此，一旦 GIP 開始發揮作用，對 GIP 的對抗就會開始產生一些負面影響，我對此並不感到驚訝。

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作用，可以減少潛在的噁心和嘔吐。再說一次，我認為也許在較高劑量下，你可能會看到一些具有拮抗作用的相反效果的跡象。我們很高興做出了這個決定。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 has 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，在之前的兩次財報電話會議上，至少已經有人承認，CMO 將成為未來腸促胰島素供應的一部分。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，你想回答這個問題嗎？

Sure. I've mentioned on this call as well that we have a 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。我在這次電話會議上也提到，我們有一個非常廣泛的擴張計劃，其中包括第三方。雖然我們的策略一直是更多地進行內部開發，但我們也有第三方。是的，我們看到了 Novo 昨天發布的有關收購 Catalent 意圖的公告。我們確實對這筆交易有疑問，需要了解更多。

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，Catalent 是該行業商業和管道產品不可或缺的一部分或製造商，尤其是在糖尿病和肥胖症領域。我們也有針對這些網站的產品。因此，我們今天的重點是確保患者的藥品供應不間斷，同時，隨著我們關注並獲得有關此擬議交易的更多信息，我們打算讓 Catalent 對我們與該合約的責任。

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.

我只是想回到卡特的​​問題。鑑於禮來公司資金雄厚，且製造能力是重中之重，我的意思是，您是否可以期望透過更多的購買而不是自行開發來解決一些技術瓶頸和非同尋常的 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 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，正如我之前在與 orforglipron 相關的問題中提到的那樣，我們並不認為自己在該領域的購買或建設受到資本限制。現實情況是，目前還沒有可用的建設容量。其中大部分已在 GLP-1 領域針對領先產品進行部署，至少是大規模部署。新產能的交付週期為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.

所以現在上線的所有東西，就像我們今天提到的，我們位於北卡羅來納州康科德的大型工廠，對於該行業，當然對於禮來公司來說，都是一個巨大的產能節點。我的意思是，這是兩年半前宣布的。並且將於今年底開始生產。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.

這是為什麼呢？當然，綠地建設是困難的。重新利用很困難。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。生產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.

因此就目前而言，我認為沒有簡單的出路。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此次購買中增加產能。

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 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）將會上線更多的產能。並且將會出現像 orforglipron 或其他口服藥物這樣的新技術，以利用不同的資產基礎。

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 we are in as there will be steady gains in manufacturing over the coming several years and perhaps bigger gains after that.

所以我知道這對投資者來說是令人沮喪的，對我們來說也是令人沮喪的。對患者來說這更令人沮喪。但這就是我們所處的情況，因為未來幾年製造業將會穩定成長，之後或許會有更大的成長。

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.

您能否向我們介紹一下與雇主的接觸情況？您是否獲得了對您的藥品的獨家使用權，或者您是否被添加到了競爭對手的藥品現有使用權中？討論的性質是什麼，特別是考慮到 Zepbound 的定價更具吸引力？我估計，有了回扣，差異可能會小一點。但任何顏色都可能非常有用。

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。我認為我們之前在 Chris Schott 的問題上已經討論過這個問題。我不知道帕特里克是否還有什麼要補充，或者我們是否可以繼續。

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，我認為唯一的補充就是我們始終致力於開放取用。我們相信這對我們服務的提供者和患者來說很重要。因此，當談到雇主選擇時，這也是我們的目標。我們認為，儘管 Zepbound 擁有同類最佳的配置，但其定價卻比競爭對手低 22%，這一舉措也表明員工選擇權的增加和增強是一個良好的信號。

The next question is from Andrew Baum from Citi.

下一個問題來自花旗銀行的 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 fill finish 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 2032 年後（即有可能推出仿製藥司美格魯肽的時期）的情境規劃？人們似乎對產能擴張有著濃厚的興趣和投資。現在顯然，這很複雜，正如您所概述的，不僅要考慮 API，還要考慮填充完成、IP 和其餘部分。但我只是好奇，您如何看待這個問題，以便為您的業務在未來免受逐步編輯和其他影響，並考慮您更廣泛的腸促胰島素產品組合的影響。

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，我將交給 Anat 來談論 2032 年及以後的情況。

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 patent expirees, 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，實際上我們也確實著眼於更遠的未來。從我們的角度來看，我們的業務是一項長期業務。這不是一個每年或每兩年都會改變的業務。因此，我們確實會從商業產品和即將推出的產品兩個方面著眼於長遠前景。當我們思考專利到期事件時，無論是我們的產品還是競爭對手的產品，我們應對這一事件的方式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，為了提高我們自身創新的標準，我們不會等待它的發生或透過競爭來實現，而是將一些能為患者帶來顯著改善結果的產品推向市場。因此在這個特定的例子中，您使用 GLP。毫無疑問，tirzepatide 為長期體重管理患者帶來了更高的減肥標準。丹在評論中提到的瑞他妥肽目前處於第三階段，有可能為患者帶來進一步改善的治療效果。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.

在產能方面，其中一個問題是，考慮到專利最終會到期，公司是否應該建設，我們確實會考慮這一點，並且著眼於長遠前景。但可以肯定的是，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康科德還是在三角研究園，兩者加起來大約是 40 億美元的投資，考慮到長期機會的規模，這無疑是對我們資本的一項很好的投資。

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該領域的潛力時，一般來說，它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總額就達到約 110 億美元。除此之外，我們還擁有遍佈全球的龐大生產網絡，主要集中在美國和歐洲。因此，當您考慮進入該領域時，它將需要一些重大的資本投入。

The next question is from Tim Anderson from Wolfe Research.

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

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就是今年的安進數據。他們的訊息是關於延長服藥頻率、每月服藥，然後可能在治療後獲得更大的減肥效果。那麼，您能否評論一下您對每月或更長時間的延長給藥的價值的看法？那麼您是否相信關於療效在治療結束後仍能持續的論點？或者這只是因為這種藥物的藥效持續時間更長？

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 expected to remain there after a month or 2.

我先從第二個問題開始，然後派崔克可能會評估這裡的潛在價值，儘管這對安進來說可能是個好問題。聽著，我認為我在該出版物中看到的可持續性數據有點令人失望。這是一種針對抗體半衰期非常高劑量的藥物。因此，僅根據血漿濃度，預計該濃度將在一個月或兩個月後保持不變。

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。但我們觀察到的是，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，體重減輕的程度低於我們確定將分子帶到第三階段所需看到的程度。而可持續性似乎也沒有什麼差別。

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.

我唯一的補充是，當我們進行市場研究時，便利性當然是一個因素。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，tirzepatide 仍然是肥胖症的基礎治療方法，但同時增加了 retatrutide 和 orforglipron，並且還有機會研究額外的非減肥依賴性藥理學選擇，以補充我們正在研發的資產。

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

謝謝你們兩位。戴夫，你想幫我們結束這段關係嗎？

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，絕對是。很好，喬。謝謝。我們感謝今天參加的每個人，當然也感謝你們對公司的關注。 2023 年對禮來公司來說是真正有成果的一年。在今天的有力指引下，我們期待 2024 年繼續保持這一勢頭。再次感謝您的來電。如果您還有其他未解答的問題，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，今天的會議到此結束。本次會議將於下午 1 點開始提供重播。今天持續到 2 月 20 日午夜。您可隨時撥打 (800) 332-6854 並輸入存取碼 187676 存取重播系統。國際撥號者可撥打 (973) 528-0005。感謝您的參與。現在您可以斷開線路了。