禮來公司 (LLY) 2022 Q3 法說會逐字稿

Ladies and gentlemen, thank you for standing by, and welcome to the Lilly Q3 2022 Earnings Conference Call. (Operator Instructions) And as a reminder, your conference is being recorded. 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，感謝您的支持，歡迎參加禮來公司 2022 年第三季度收益電話會議。 （操作員說明）作為提醒，您的會議正在錄製中。我現在想將會議轉交給您的主持人，投資者關係高級副總裁喬·弗萊徹（Joe Fletcher）。請繼續。

Thank you, Lois, and good morning. Thank you for joining us for Eli Lilly and Company's Q3 2022 Earnings Call. I'm Joe Fletcher, Senior Vice President of Investor Relations. And joining me on today's call are Dave Ricks, Lilly's Chair and CEO; Anat Ashkenazi, Chief Financial Officer; Dr. Dan Skovronsky, Chief Scientific and Medical Officer; Anne White, President of Lilly Neuroscience; Ilya Yuffa, President of Lilly International; Jake Van Naarden, CEO of Loxo@Lilly; Mike Mason, President of Lilly Diabetes; and Patrik Jonsson, President of Lilly Immunology and Lilly USA. We're also joined by Mike Sprengnether, Kento Ueha and Lauren Zierke of the Investor Relations team.

謝謝你，路易斯，早上好。感謝您參加禮來公司 2022 年第三季度財報電話會議。我是投資者關係高級副總裁喬·弗萊徹。和我一起參加今天電話會議的還有禮來公司的董事長兼首席執行官戴夫·里克斯（Dave Ricks）； Anat Ashkenazi，首席財務官； Dan Skovronsky 博士，首席科學和醫學官；禮來公司神經科學總裁 Anne White；禮來國際總裁 Ilya Yuffa； Loxo@Lilly 首席執行官 Jake Van Naarden；禮來糖尿病總裁 Mike Mason；以及禮來免疫學和禮來美國公司總裁 Patrik Jonsson。投資者關係團隊的 Mike Sprengnether、Kento Ueha 和 Lauren Zierke 也加入了我們的行列。

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

在這次電話會議期間，我們預計會根據我們目前的預期做出預測和前瞻性陳述。由於多種因素，我們的實際結果可能存在重大差異，包括幻燈片 3 中列出的因素。有關可能導致實際結果產生重大差異的因素的其他信息包含在我們最新提交的 10-K 表格和後續 10-Q 和 8-K 表格中與證券交易委員會。

The information we provide about our products and pipeline is for the benefit of the investment community. It is 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信息是為了投資界的利益。它不是為了促銷，也不足以做出處方決定。當我們過渡到我們準備好的評論時，請注意我們的評論將集中在非公認會計準則財務指標上。

Now I'll turn the call over to Dave.

現在我將把電話轉給戴夫。

Well, thanks, Joe. Over the last 3 months, we continued to successfully execute our strategy. On the commercial front, we drove strong volume-based growth of our recently launched medicines, including Mounjaro, which has seen an impressive initial uptick. At the same time, we advanced our late-phase pipeline, progressing towards potential launches of 4 new medicines by the end of next year while also investing in our early-stage pipeline and new modalities like gene therapy. To meet the growing demand for our products and prepare for future launches, we have also continued to invest in expansion of our manufacturing footprint.

好吧，謝謝，喬。在過去的 3 個月裡，我們繼續成功地執行我們的戰略。在商業方面，我們推動了我們最近推出的藥物的基於銷量的強勁增長，包括 Mounjaro，它的初始增長令人印象深刻。與此同時，我們推進了我們的後期管道，爭取在明年年底前推出 4 種新藥，同時還投資於我們的早期管道和基因治療等新模式。為了滿足對我們產品不斷增長的需求並為未來的發布做準備，我們還繼續投資擴大我們的製造足跡。

I'd highlight 2 areas of high unmet need where Lilly is progressing new medicines to improve patient outcomes: obesity and Alzheimer's disease. In obesity, we are pleased that the FDA has granted Fast Track designation for tirzepatide for adults with obesity, enabling us to potentially bring this promising medicine to patients even sooner. We're also initiating SURMOUNT-MMO, our Phase III morbidity and mortality in obesity study to evaluate improved outcomes for patients with obesity.

我要強調兩個高度未滿足需求的領域，禮來公司正在開發新藥以改善患者的預後：肥胖症和阿爾茨海默病。在肥胖症方面，我們很高興 FDA 已授予肥胖成人替西帕肽的快速通道指定，使我們能夠更快地將這種有前途的藥物帶給患者。我們還啟動了 SURMOUNT-MMO，這是我們的 III 期肥胖症發病率和死亡率研究，以評估肥胖患者的改善結果。

In Alzheimer's disease, our Phase III TRAILBLAZER-ALZ 2 study for donanemab continues to progress towards a top line readout in mid-2023. And we continue to work with the FDA to pursue an accelerated approval based on our TRAILBLAZER-ALZ data. We also announced completion of our submission for lebrikizumab in atopic dermatitis in both the U.S. and the EU. With already completed submissions for donanemab, pirtobrutinib, mirikizumab, we are excited by the potential to launch 4 new medicines between now and the end of 2023. We are experiencing an unprecedented rate of new product launches for Lilly and undoubtedly one of the most impressive rates in our industry.

在阿爾茨海默病方面，我們針對 donanemab 的 III 期 TRAILBLAZER-ALZ 2研究繼續朝著 2023 年中期的頂線讀數前進。我們將繼續與 FDA 合作，根據我們的 TRAILBLAZER-ALZ 數據尋求加速批准。我們還宣布完成在美國和歐盟提交用於治療特應性皮炎的 lebrikizumab。由於 donanemab、pirtobrutinib、mirikizumab 的提交已經完成，我們對從現在到 2023 年底推出 4 種新藥的潛力感到興奮。我們正在經歷禮來（Lilly）前所未有的新產品發布速度，無疑是最令人印象深刻的速度之一在我們的行業。

Turning to our strategic deliverables on Slide 4. Q3 revenue grew 7% in constant currency. Worldwide volume grew a robust 14%. Key product growth grew 19% and now account for 70% of our core business revenue, a reflection of the youth and durability of our marketed product portfolio. We're encouraged to see the continued global adoption of products like Verzenio, Taltz, Jardiance and our [anchor 10] medicines, including Mounjaro and Trulicity.

轉向我們在幻燈片 4 上的戰略交付成果。按固定匯率計算，第三季度收入增長了 7%。全球銷量強勁增長 14%。關鍵產品增長了 19%，現在占我們核心業務收入的 70%，這反映了我們營銷產品組合的年輕和耐用性。我們很高興看到 Verzenio、Taltz、Jardiance 和我們的 [anchor 10] 藥物（包括 Mounjaro 和 Trulicity）等產品在全球範圍內的持續採用。

Our non-GAAP gross margin was 79% in Q3, which is in line with the same period last year. Our non-GAAP operating margin was 28.9%, which includes a negative impact of approximately 90 basis points attributed to acquired in-process R&D and development milestone charges.

我們第三季度的非美國通用會計準則毛利率為 79%，與去年同期持平。我們的非美國通用會計準則營業利潤率為 28.9%，其中包括約 90 個基點的負面影響，這歸因於收購的研發過程中和開發里程碑費用。

For pipeline milestones, we shared several important updates since our Q2 earnings call, including FDA Fast Track designation for tirzepatide for adults with obesity, with completion of a rolling submission expected by mid-2023; EU and Japan approval for Mounjaro for the treatment of adults with type 2 diabetes; U.S. and EU submission of lebrikizumab for moderate to severe atopic dermatitis; and FDA accelerated approval for Retevmo in RET fusion-positive advanced or metastatic solid tumors regardless of tumor type and traditional approval in adults with locally advanced or metastatic RET fusion-positive non-small cell lung cancer.

對於管道里程碑，我們分享了自第二季度財報電話會議以來的幾項重要更新，包括 FDA 快速通道指定用於成人肥胖的 tirzepatide，預計在 2023 年年中完成滾動提交；歐盟和日本批准 Mounjaro 用於治療成人 2 型糖尿病；美國和歐盟提交用於治療中度至重度特應性皮炎的 lebrikizumab；和 FDA 加速批准 Retevmo 用於 RET 融合陽性晚期或轉移性實體瘤，無論腫瘤類型如何，以及傳統批准用於患有局部晚期或轉移性 RET 融合陽性非小細胞肺癌的成人。

Dan will discuss this in more detail later, but we are excited to have announced the acquisition of Akouos, which aims to accelerate efforts in gene therapies that promise to restore, improve and preserve hearing for patients living with disabling hearing loss. This acquisition demonstrates our continued commitment to advancing genetic medicine at Lilly. And finally, we distributed nearly $900 million in dividends to our shareholders.

Dan 將在稍後更詳細地討論這一點，但我們很高興宣布收購 Akouos，該公司旨在加速基因療法的努力，這些療法有望恢復、改善和保護聽力損失患者的聽力。此次收購表明我們繼續致力於在禮來推進基因醫學。最後，我們向股東派發了近 9 億美元的股息。

On Slide 5, you'll see a list of key events since our Q2 earnings call, including several important personnel, COVID-19 antibody and ESG updates. We announced the upcoming retirement of Steve Fry, our Executive Vice President of Human Resources and Diversity, following more than 35 years at our company. I'd like to thank Steve for playing a key role in advancing our diversity, equity and inclusion agenda and leading our efforts to be the premier employer in our region and our sector.

在幻燈片 5 上，您將看到自我們第二季度財報電話會議以來的關鍵事件列表，包括幾個重要人員、COVID-19 抗體和 ESG 更新。我們宣布即將退休，我們的人力資源和多元化執行副總裁 Steve Fry 在我們公司工作了超過 35 年。我要感謝史蒂夫在推進我們的多元化、公平和包容議程方面發揮了關鍵作用，並帶領我們努力成為我們地區和行業的首要雇主。

We also welcome Eric Dozier, who will succeed Steve. Eric has nearly 25 years of experience at Lilly and a strong track record of developing people and teams that deliver impressive business results. I'm confident he is the right leader to progress our people strategy, which is vital for Lilly to achieve our ambitious growth objectives ahead.

我們也歡迎 Eric Dozier，他將接替 Steve。 Eric 在禮來 (Lilly) 擁有近 25 年的工作經驗，並且在培養能夠提供令人印象深刻的業務成果的人員和團隊方面有著良好的記錄。我相信他是推進我們的人才戰略的合適領導者，這對於禮來實現我們未來雄心勃勃的增長目標至關重要。

In August, we began to make our COVID-19 antibody, bebtelovimab, available for purchase to states, hospitals and certain other providers through a sole distributor. In Q3, we shipped an additional 600,000 -- or 60,000, I should say, doses of bebtelovimab to the U.S. government for approximately $110 million. These are to be used for the financially vulnerable patients through a product replacement program. At this time, we are not anticipating any further U.S. government orders for bebtelovimab.

8 月，我們開始通過獨家經銷商向各州、醫院和某些其他供應商提供 COVID-19 抗體 bebtelovimab。在第三季度，我們以大約 1.1 億美元的價格向美國政府額外運送了 600,000 - 或者說是 60,000 劑 bebtelovimab。這些將通過產品更換計劃用於經濟上脆弱的患者。目前，我們預計美國政府不會有任何進一步的 bebtelovimab 訂單。

With regards to our ESG efforts, we published our inaugural Sustainability Bond Allocation and Impact Report, highlighting the allocation of approximately EUR 128 million across a range of sustainability projects since the issuance of the sustainability bond in September of '21. For more information about this and the many other aspects of our ESG program, you can visit our Lilly ESG website.

關於我們的 ESG 工作，我們發布了首份可持續發展債券分配和影響報告，強調自 21 年 9 月發行可持續發展債券以來，已在一系列可持續發展項目中分配了約 1.28 億歐元。有關此方面以及我們 ESG 計劃的許多其他方面的更多信息，您可以訪問我們的禮來 ESG 網站。

Now I'll turn the call over to Anat for a more detailed review of our Q3 results.

現在，我將把電話轉給 Anat，以更詳細地審查我們的第三季度業績。

Thanks, Dave. Before I review the financial results for Q3, let me highlight a change in how we expect to communicate our acquired IPR&D and development milestone charges. In mid-October, we filed an 8-K with the SEC to provide investors earlier clarity on the impact from acquired IPR&D and development milestone charges for Q3. In future quarters, we generally expect to provide this information through quarterly updates on our Investor Relations website.

謝謝，戴夫。在我回顧第三季度的財務業績之前，讓我強調一下我們期望如何傳達我們獲得的 IPR&D 和開發里程碑費用的變化。 10 月中旬，我們向 SEC 提交了一份 8-K 文件，以便讓投資者更早地了解第三季度收購的 IPR&D 和開發里程碑費用的影響。在未來幾個季度，我們通常希望通過我們的投資者關係網站上的季度更新來提供這些信息。

Now moving to our results. Slide 6 summarizes financial performance in the third quarter of 2022, and I'll focus my overall comments on non-GAAP performance. A few notable items affected year-over-year comparisons in Q3. Foreign exchange rates had a roughly 430 basis point impact on revenue this quarter as Q3 revenue grew by 2% or 7% on a constant currency basis. We recognized $86 million of revenue related to a sales collaboration agreement for the rights to sell and distribute Mounjaro in Japan. We experienced the first full quarter impact of Alimta's U.S. patent expiry, and the increase in sales of COVID-19 antibodies and the decrease in sales of Olumiant for the treatment of COVID-19 impacted our results.

現在轉到我們的結果。幻燈片 6 總結了 2022 年第三季度的財務業績，我將把我的總體評論集中在非 GAAP 業績上。一些值得注意的項目影響了第三季度的同比比較。由於第三季度收入按固定匯率計算增長了 2% 或 7%，因此本季度外匯匯率對收入的影響約為 430 個基點。我們確認了與在日本銷售和分銷 Mounjaro 的銷售合作協議相關的 8600 萬美元收入。我們經歷了 Alimta 美國專利到期的第一個完整季度的影響，COVID-19抗體銷售額的增加和用於治療 COVID-19的 Olumiant 銷售額的下降影響了我們的業績。

When excluding revenue from Alimta, which is now off patent across the EU, Japan and the U.S., COVID-19 antibodies and Olumiant for the treatment of COVID-19, revenue grew 9% for the quarter or 14% in constant currency, highlighting solid momentum for our core business.

剔除來自 Alimta（現已在歐盟、日本和美國失去專利）、COVID-19 抗體和用於治療 COVID-19 的 Olumiant 的收入時，本季度收入增長 9% 或按固定匯率計算增長 14%，突顯穩健為我們的核心業務提供動力。

Gross margin was roughly flat year-over-year. The impact of lower realized prices and increased expenses due to inflation and logistics costs were offset by favorable product mix, including the impact of lower sales of Olumiant for the treatment of COVID-19 and the favorable impact of foreign exchange rates.

毛利率與去年同期基本持平。由於通貨膨脹和物流成本導致的實際價格下降和費用增加的影響被有利的產品組合所抵消，包括用於治療 COVID-19 的 Olumiant 銷售額下降的影響以及匯率的有利影響。

Total operating expenses increased 1% this quarter. Growth in marketing, selling and administrative expenses and R&D expenses were largely offset by lower acquired IPR&D and development milestone charges that reduced operating expense growth by nearly 350 basis points. Marketing, selling and administrative expenses increased 2%, primarily driven by the increased costs associated with the launch of Mounjaro, partially offset by the favorable impact of foreign exchange rates. R&D expenses increased 6%, driven by higher development expense for late-stage assets, partially offset by the favorable impact of foreign exchange rates and lower development expenses for COVID-19 antibodies.

本季度總運營費用增長了 1%。營銷、銷售和管理費用以及研發費用的增長在很大程度上被較低的知識產權和開發里程碑費用所抵消，這使運營費用增長減少了近 350 個基點。營銷、銷售和行政費用增長了 2%，主要是由於與推出 Mounjaro 相關的成本增加，部分被外匯匯率的有利影響所抵消。研發費用增長 6%，受後期資產開發費用增加的推動，部分被外匯匯率的有利影響和 COVID-19抗體開發費用降低所抵消。

Operating income increased 6% in Q3, primarily due to higher gross margin, partially offset by higher operating expenses. Operating income as a percent of revenue was 28.9%, which includes a negative impact of approximately 90 basis points attributable to the acquired IPR&D and development milestone charges.

第三季度營業收入增長 6%，主要是由於較高的毛利率，部分被較高的營業費用所抵消。營業收入佔收入的百分比為 28.9%，其中包括因收購的 IPR&D 和開發里程碑費用而產生的約 90 個基點的負面影響。

Our Q3 effective tax rate was 10.7%, a decrease of 360 basis points compared to the same period in 2021. This decrease was primarily driven by the favorable tax impact related to the implementation of the 2017 Tax Act.

我們第三季度的有效稅率為 10.7%，與 2021 年同期相比下降了 360 個基點。這一下降主要是由於與 2017 年稅法實施相關的有利稅收影響。

At the bottom line, earnings per share increased approximately 12% this quarter to $1.98 per share. Acquired IPR&D and development milestone charge had a negative impact of $0.06 in Q3 2022 compared to $0.17 in the same period last year.

最重要的是，本季度每股收益增長了約 12%，達到每股 1.98 美元。收購的 IPR&D 和開發里程碑費用在 2022 年第三季度產生了 0.06 美元的負面影響，而去年同期為 0.17 美元。

On Slide 8, we quantify the effect of price, rate and volume on revenue growth. This quarter, foreign exchange movements primarily related to the weakening of the euro against the U.S. dollar decreased revenue by 4%.

在幻燈片 8 中，我們量化了價格、費率和數量對收入增長的影響。本季度，主要與歐元兌美元走弱有關的外匯走勢使收入減少了 4%。

Moving to our performance by key geography. This quarter, U.S. revenue grew 11% driven by volume growth of 15%. Excluding revenue from Alimta, COVID-19 antibodies and Olumiant for the treatment of COVID-19, revenue in the U.S. increased 20% driven primarily by key growth products. U.S. volume growth was partially offset by a net price decline of 4% driven primarily by lower realized prices for Humalog due to segment mix and the list price reduction for Insulin Lispro injection.

按關鍵地理位置轉移到我們的表現。本季度，在銷量增長 15% 的推動下，美國收入增長了 11%。不包括來自 Alimta、COVID-19 抗體和 Olumiant 用於治療 COVID-19 的收入，美國的收入增長了 20%，主要受關鍵增長產品的推動。美國銷量增長被淨價下降 4% 部分抵消，這主要是由於細分市場組合導致 Humalog 實現價格下降和胰島素 Lispro 注射液的標價下降。

Moving to Europe. Revenue grew 11% in constant currency, driven primarily by volume growth for Trulicity, Jardiance, Verzenio and Taltz. We are encouraged by the momentum of our business in Europe and expect continued growth as the impact from the patent expiry for Alimta, which lost exclusivity in June 2021, recede from base period comparison.

搬到歐洲。按固定匯率計算，收入增長了 11%，主要受 Trulicity、Jardiance、Verzenio 和 Taltz 銷量增長的推動。我們對我們在歐洲的業務發展勢頭感到鼓舞，並預計隨著 Alimta 專利到期的影響（該公司於 2021 年 6 月失去排他性）從基期比較中消退，我們將繼續增長。

For Japan, Q3 revenue decreased by 2% in constant currency. The growth of our newer medicine and revenue related to a sales collaboration agreement for the rights to sell and distribute Mounjaro in Japan was more than offset by the continued impact of declines in off-patent products, primarily Cymbalta and Alimta, which both faced generic entry in June 2021. We expect a return to growth in Japan beginning in 2023 as we continue to scale our key growth products and the impact of patent expiration subsides.

在日本，按固定匯率計算，第三季度的收入下降了 2%。我們的新藥增長和與在日本銷售和分銷 Mounjaro 權利的銷售合作協議相關的收入增長被非專利產品（主要是 Cymbalta 和 Alimta）下降的持續影響所抵消，這兩個產品都面臨仿製藥進入2021 年 6 月。我們預計，隨著我們繼續擴大關鍵增長產品的規模以及專利到期的影響消退，日本將從 2023 年開始恢復增長。

In China, revenue declined 10% in constant currency as we continue to be impacted by the Zero-COVID policy measures. We're also seeing the impact of increased competitive pressures for Tyvyt from local competitors with NRDL access. In addition, we experienced the first full quarter of the pricing impact of volume-based procurement for Humalog. As we expect to maintain a high level of access for our innovative portfolio, we believe our volume should accelerate to drive net growth in the future.

在中國，由於我們繼續受到零疫情政策措施的影響，按固定匯率計算的收入下降了 10%。我們還看到，擁有 NRDL 訪問權的本地競爭對手對 Tyvyt 的競爭壓力增加的影響。此外，我們在第一個完整季度對 Humalog 的基於數量的採購的定價影響進行了體驗。由於我們希望保持對我們創新產品組合的高水平訪問，我們相信我們的數量應該會加速以推動未來的淨增長。

Revenue in the rest of the world decreased 6% in constant currency in Q3 primarily driven by customer buying patterns. The year-to-date growth of 8% in constant currency in this region is more representative of underlying trends.

第三季度全球其他地區的收入按固定匯率計算下降了 6%，主要受客戶購買模式的推動。該地區今年迄今以固定匯率計算的 8% 的增長更能代表基本趨勢。

As shown on Slide 9, our key growth products continue to drive robust worldwide volume growth. These products drove approximately 18 percentage points of volume growth this quarter and continue to underpin our current performance and future outlook.

如幻燈片 9 所示，我們的主要增長產品繼續推動全球銷量強勁增長。這些產品在本季度推動了約 18 個百分點的銷量增長，並繼續支撐我們當前的業績和未來展望。

Slide 10 further highlights the contribution of our key growth products. This quarter, these brands grew 19% or 25% in constant currency, generated $4.6 billion in sales and made up 70% of our core business revenue. Products like Verzenio, Taltz in dermatology and Jardiance have outpaced competitors growth and are leaders in new-to-brand share of market within their respective classes.

幻燈片 10 進一步突出了我們主要增長產品的貢獻。本季度，這些品牌按固定匯率計算增長了 19% 或 25%，產生了 46 億美元的銷售額，占我們核心業務收入的 70%。 Verzenio、Taltz in dermatology 和 Jardiance 等產品的增長速度超過了競爭對手，並且在各自類別中的新品牌市場份額方面處於領先地位。

In the injectable incretin market, we continue to see significant opportunity for further class growth. In addition to Mounjaro's successful launch in the U.S., Trulicity has continued to experience strong growth globally. To date, our incretin manufacturing production is ahead of our internal plan, and we remain focused on sustaining this performance.

在註射劑腸促胰島素市場，我們繼續看到進一步增長的重要機會。除了 Mounjaro 在美國的成功推出外，Trulicity 在全球範圍內繼續保持強勁增長。迄今為止，我們的腸促胰島素製造生產領先於我們的內部計劃，我們仍然專注於維持這一業績。

Strong demand for Trulicity, partially due to ongoing limited availability of competitor GLP-1, continues to challenge our ability to meet expanding demand in most international markets. In those situations, we're working hard to supply market demand while minimizing impact to existing patients, including communication in these markets not to initiate new patients on Trulicity. In the U.S., script volume remains robust. And while we build more capacity, wholesalers may experience intermittent restocking delays of Trulicity orders.

對 Trulicity 的強勁需求，部分是由於競爭對手 GLP-1 的持續供應有限，繼續挑戰我們滿足大多數國際市場不斷擴大的需求的能力。在這種情況下，我們正在努力滿足市場需求，同時盡量減少對現有患者的影響，包括在這些市場進行溝通，以免在 Trulicity 上啟動新患者。在美國，劇本數量依然強勁。在我們建立更多產能的同時，批發商可能會遇到 Trulicity 訂單的間歇性補貨延遲。

Moving to Slide 11. We're pleased with the rapid uptake of Mounjaro in the first 4 months since launch. Approximately 70% of Mounjaro's new therapy starts are patients naive to the type 2 diabetes injectable incretin class and less than 10% for switches from Trulicity. We are progressing peer negotiations and have more than doubled the level of access to approximately 45% of total commercial and Part D lives. And as we expand access, the proportion of paid scripts should start to increase.

轉到幻燈片 11。我們很高興 Mounjaro 在推出後的前 4 個月內迅速普及。 Mounjaro 大約 70% 的新療法開始是對 2 型糖尿病可注射腸促胰島素類的患者天真，而從 Trulicity 轉換的患者不到 10%。我們正在推進同行談判，並將獲得約 45% 的商業和 D 部分總生命的機會水平提高了一倍以上。而且隨著我們擴大訪問範圍，付費腳本的比例應該會開始增加。

Our focus is to make Mounjaro available for type 2 diabetes patients, and we intend to take actions designed to ensure access and supply for these patients. These actions may negatively impact prescription volume but are not expected to impact net revenue.

我們的重點是讓 Mounjaro 可用於 2 型糖尿病患者，我們打算採取旨在確保這些患者獲得和供應的行動。這些行動可能會對處方量產生負面影響，但預計不會影響淨收入。

We have seen unprecedented demand for Mounjaro's type 2 diabetes launch in the U.S., bolstered by strong efficacy and a positive customer experience. Availability of competitor's incretin also is a key factor as we assess Mounjaro's demand and supply.

我們看到 Mounjaro 在美國推出 2 型糖尿病的需求空前，這得益於強大的療效和積極的客戶體驗。在我們評估 Mounjaro 的需求和供應時，競爭對手的腸促胰島素的可用性也是一個關鍵因素。

To meet this rapidly growing demand across our incretin business, we have plans to add substantial additional manufacturing capacity. In 2023, we expect the RTP site in North Carolina to become fully operational and that capacity, coupled with additional actions and extensions in other sites, will result in doubling Lilly's incretin manufacturing capacity at the end of 2023.

為了滿足我們腸促胰島素業務快速增長的需求，我們計劃增加大量額外的製造能力。 2023 年，我們預計北卡羅來納州的 RTP 工廠將全面投入運營，該產能，加上其他工廠的額外行動和擴建，將導緻禮來公司的腸促胰島素生產能力在 2023 年底翻番。

On Slide 12, we provide an update on capital allocation. For the first 9 months of the year, we invested $6.8 billion to drive our future growth through a combination of R&D expenditures, business development outlays and capital investments. In addition, we returned approximately $2.7 billion to shareholders in dividend and repurchased $1.5 billion in stock. Our capital allocation priorities are to fund our key marketed products and expected new launches, bolster manufacturing capacity, invest in our pipeline, pursue opportunities for external innovation to augment our future growth prospects and return excess capital to shareholders.

在幻燈片 12 中，我們提供了資本配置的最新信息。今年前 9 個月，我們投資了 68 億美元，通過結合研發支出、業務發展支出和資本投資來推動我們未來的增長。此外，我們向股東返還了大約 27 億美元的股息，並回購了 15 億美元的股票。我們的資本配置優先事項是為我們的主要上市產品和預期的新產品提供資金、增強製造能力、投資我們的管道、尋求外部創新機會以擴大我們未來的增長前景並將多餘的資本返還給股東。

Slide 13 is our updated 2022 financial guidance. Our full year revenue outlook now includes an additional $300 million of headwinds from foreign exchange rates since our previous guidance update for a total impact of roughly $1 billion of foreign exchange headwinds on revenue for the full year compared to our original guidance. Our outlook for gross margin, SG&A and research and development remains unchanged.

幻燈片 13 是我們更新的 2022 年財務指南。自我們之前的指引更新以來，我們的全年收入展望現在包括額外 3 億美元的外匯逆風，與我們最初的指引相比，全年的外匯逆風對全年收入的總影響約為 10 億美元。我們對毛利率、SG&A 和研發的展望保持不變。

Our guidance now includes acquired IPR&D and development milestone charges of approximately $670 million, reflecting total charges in the first 9 months of the year. We have not recognized material acquired IPR&D or development milestone charges to date in Q4. And this guidance does not include any impact from the potential acquisition -- for potential business development or acquisition in the remainder of the year, including pending acquisition of Akouos. Our non-GAAP operating margins remain unchanged at approximately 29%.

我們的指導現在包括大約 6.7 億美元的收購 IPR&D 和開發里程碑費用，反映了今年前 9 個月的總費用。迄今為止，我們尚未在第四季度確認材料獲得的 IPR&D 或開發里程碑費用。本指南不包括潛在收購的任何影響——對今年剩餘時間的潛在業務發展或收購，包括對 Akouos 的未決收購。我們的非美國通用會計準則營業利潤率保持不變，約為 29%。

On a reported basis, operating margin is now expected to be approximately 26% driven by the intangible asset impairment for our GBA1 Gene Therapy due to changes in estimated launch timing. Our non-GAAP range for other income and expense remains unchanged. On a reported basis, other income and expense is now expected to be expense in the range of $600 million to $700 million, reflecting the net impact of net losses on investments in equity securities during Q3 2022.

根據報告，由於估計推出時間的變化，我們的 GBA1 基因療法的無形資產減值導致營業利潤率目前預計約為 26%。我們對其他收入和支出的非公認會計原則範圍保持不變。根據報告，其他收入和費用現在預計將在 6 億美元至 7 億美元之間，反映了 2022 年第三季度淨虧損對股本證券投資的淨影響。

Our tax rate and EPS in the first 9 months of the year includes a favorable impact of the provision in the 2017 Tax Act that requires capitalization and amortization of research and development expenses for tax purposes. Our financial guidance for the full year continues to assume this provision will be deferred or repealed by Congress, effective for the full year 2022.

我們今年前 9 個月的稅率和每股收益包括 2017 年稅法中要求為稅收目的對研發費用進行資本化和攤銷的規定的有利影響。我們對全年的財務指導繼續假設該條款將被國會推遲或廢除，自 2022 年全年生效。

Assuming this deferral or repeal occurs before the end of the year, we expect our Q4 non-GAAP tax rate to be approximately 22%, which includes the cumulative tax impact of immediately expensing research and development costs for the full year 2022. If this provision is not deferred or repealed effective this year, then we would expect our reported and non-GAAP tax rate to be approximately 10% to 11%.

假設這種推遲或廢除發生在年底之前，我們預計我們的第四季度非公認會計原則稅率約為 22%，其中包括立即支出 2022 年全年研發成本的累積稅收影響。如果這項規定今年沒有延期或廢除，那麼我們預計我們報告的和非公認會計原則的稅率約為 10% 至 11%。

Based on these changes, we have lowered our reported EPS guidance by $0.46 to now be in the range of $6.50 to $6.65 per share and lowered our 2022 non-GAAP EPS guidance by $0.20 to be in the range of $7.70 to $7.85. The $0.20 reduction in our non-GAAP EPS range is driven by the negative impact of foreign exchange rates as well as the $0.06 impact from the incremental acquired IPR&D and development milestone charges in Q3.

基於這些變化，我們將報告的每股收益指引下調了 0.46 美元，目前在每股 6.50 美元至 6.65 美元的範圍內，並將我們的 2022 年非美國通用會計準則每股收益指引下調了 0.20 美元，至 7.70 美元至 7.85 美元的範圍內。我們的非公認會計原則每股收益範圍減少 0.20 美元是由於匯率的負面影響以及第三季度增加的收購 IPR&D 和開發里程碑費用的 0.06 美元影響。

Now before I turn the call over to Dan, I'd like to provide a few thoughts on the pushes and pulls across the P&L as you begin to think about next year. Starting with revenue, we're confident in the growth outlook of our core business. We expect to build on the positive momentum across our key growth products, including the continued strong launch of Mounjaro and launches of new products. While we anticipate that initial revenue from our next wave of potential launches will be modest in 2023 with only partial revenue, we do expect that donanemab, pirtobrutinib, mirikizumab and lebrikizumab will serve as additional catalysts for continued growth.

現在，在我將電話轉給 Dan 之前，我想在您開始考慮明年時提供一些關於 P&L 的推動和拉動的想法。從收入開始，我們對核心業務的增長前景充滿信心。我們預計將在我們的主要增長產品的積極勢頭基礎上再接再厲，包括繼續強勁推出 Mounjaro 和推出新產品。雖然我們預計 2023 年我們下一波潛在推出的初始收入將是適度的，只有部分收入，但我們確實預計 donanemab、pirtobrutinib、mirikizumab 和 lebrikizumab 將成為持續增長的額外催化劑。

In 2023, we will see the full year impact of Alimta's patent expiry in the U.S., where new generics have eroded Alimta sales starting mid-Q2 and we anticipate a low single-digit headwind from foreign exchange rates. As for revenue from COVID-19 antibodies, we will continue to make bebtelovimab available for purchase. However, the demand for these therapies will depend not only on COVID-19 case counts but also on evolving variants and available therapies. We continue to believe that COVID-19 antibodies will not be a major driver for long-term growth for Lilly.

到 2023 年，我們將看到 Alimta 在美國專利到期的全年影響，從第二季度中期開始，新仿製藥已經侵蝕了 Alimta 的銷售額，我們預計外匯匯率將出現低個位數的逆風。至於來自 COVID-19 抗體的收入，我們將繼續提供 bebtelovimab 可供購買。然而，對這些療法的需求不僅取決於 COVID-19 病例數，還取決於不斷發展的變體和可用的療法。我們仍然相信 COVID-19 抗體不會成為禮來公司長期增長的主要動力。

We will invest in our future as we advance promising R&D opportunities, expand our manufacturing capacity and support the potential launch of multiple new products. Assuming inflation persists, we expect to see that impact in 2023 as well.

隨著我們推進有前景的研發機會、擴大我們的製造能力並支持多種新產品的潛在推出，我們將投資於我們的未來。假設通脹持續存在，我們預計 2023 年也會出現這種影響。

Also, we will be making a significant investment in one of our most important assets, our talented workforce, through increases in compensation that are partially due to inflation pressures, but also to ensure that we have the right capabilities to deliver on the promise of our future growth.

此外，我們將通過增加薪酬（部分原因是通貨膨脹壓力）對我們最重要的資產之一——我們有才華的員工隊伍進行重大投資，同時確保我們有能力兌現我們的承諾。未來的增長。

While these investments will slow our operating margin expansion in 2023, they are critical to maximizing pipeline and new launch opportunities to help sustain top-tier revenue growth and operating margin expansion over the mid- to long term. We look forward to sharing more details on our 2023 guidance call on December 13.

雖然這些投資將減緩我們在 2023 年的營業利潤率擴張，但它們對於最大限度地增加管道和新推出機會以幫助維持中長期的頂級收入增長和營業利潤率擴張至關重要。我們期待在 12 月 13 日分享 2023 年指導電話會議的更多細節。

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

現在我將把電話轉給丹，以強調研發方面的進展。

Thanks, Anat. 2022 has been another outstanding year for R&D at Lilly. In addition to Mounjaro's approval, we have now completed regulatory submissions for 4 new medicines that could all launch by the end of 2023: pirtobrutinib, mirikizumab, lebrikizumab and donanemab. In addition, we advanced our early-stage pipeline with promising next-generation assets in all of our key areas. Plus we've continued to improve our capabilities and advance our projects in our growing nucleic acid medicine portfolio.

謝謝，阿納特。 2022 年對於禮來公司的研發來說又是傑出的一年。除了 Mounjaro 的批准外，我們現在還完成了 4 種可能在 2023 年底前全部上市的新藥的監管提交：pirtobrutinib、mirikizumab、lebrikizumab 和 donanemab。此外，我們在所有關鍵領域利用有前景的下一代資產推進了我們的早期管道。此外，我們不斷提高我們的能力並推進我們不斷增長的核酸藥物組合中的項目。

Before I share an R&D update for our core business, let me briefly add to Anat's update on COVID-19 antibodies. While we've made bebtelovimab commercially available, we're also closely watching the emergence of new highly mutated strains. Based on pseudovirus data, we do not believe that bebtelovimab will neutralize against the new BQ variants. However, we do have potentially broadly neutralizing antibodies in our labs that we can consider bringing forward if there is a need and an aligned path forward with health authorities.

在我分享我們核心業務的研發更新之前，讓我簡要補充一下 Anat 關於 COVID-19 抗體的更新。雖然我們已經將 bebtelovimab 商業化，但我們也在密切關注新的高度突變菌株的出現。根據偽病毒數據，我們認為 bebtelovimab 不會中和新的 BQ 變體。但是，我們的實驗室確實有可能廣泛中和的抗體，如果有需要，我們可以考慮提出這些抗體並與衛生當局保持一致。

Moving to our core R&D portfolio. Slide 14 shows select pipeline opportunities as of October 28, and Slide 15 shows potential key events for the year. I'll cover important developments since our last earnings call by therapeutic area.

轉向我們的核心研發組合。幻燈片 14 顯示了截至 10 月 28 日的選定管道機會，幻燈片 15 顯示了今年潛在的關鍵事件。我將介紹自我們上次按治療領域召開財報電話會議以來的重要發展。

Starting with diabetes and obesity. We have several updates for tirzepatide. For type 2 diabetes, in addition to the U.S. approval of Mounjaro in Q2, we're pleased to announce recent approvals in the EU and Japan. For chronic weight management, we're pleased that the FDA has granted Fast Track designation for tirzepatide. Fast Track designation is designed to facilitate the development and expedite the review of new therapies to treat serious conditions that have the potential to fill an unmet medical need.

從糖尿病和肥胖開始。我們有幾個關於 tirzepatide 的更新。對於 2 型糖尿病，除了美國在第二季度批准 Mounjaro 之外，我們很高興地宣布最近在歐盟和日本獲得批准。對於慢性體重管理，我們很高興 FDA 已授予 tirzepatide 的快速通道指定。快速通道指定旨在促進新療法的開發和加快審查，以治療有可能滿足未滿足的醫療需求的嚴重疾病。

We plan to initiate a rolling submission this year that will be primarily based on the results from the SURMOUNT-1 trial, which is complete; and SURMOUNT-2, which is expected to be complete by the end of April 2023. Assuming positive SURMOUNT-2 results, we expect to complete the rolling submission with these data in mid-2023 for potential regulatory action as early as late next year. We're working hard to bring tirzepatide to adults living with obesity as soon as we can.

我們計劃今年啟動滾動提交，主要基於 SURMOUNT-1 試驗的結果，該試驗已完成；和 SURMOUNT-2，預計將於 2023 年 4 月底完成。假設 SURMOUNT-2 結果是積極的，我們預計將在 2023 年年中完成滾動提交這些數據，以便最早在明年年底採取潛在的監管行動。我們正在努力盡快將替西帕肽帶給患有肥胖症的成年人。

We also presented the trial design of tirzepatide's SURMOUNT-MMO, our Phase III morbidity and mortality in obesity study. SURMOUNT-MMO evaluates treatment with tirzepatide compared to placebo in adults living with obesity without diabetes and measures the effects of tirzepatide on a broad set of outcomes beyond traditional cardiovascular events. As our primary endpoint, we are measuring the occurrence of a cardiovascular event from a 5-point CV composite that includes all-cause mortality. We've also incorporated key secondary endpoints, including traditional MACE 3 events, reducing the risk of developing type 2 diabetes and adverse renal outcomes.

我們還介紹了 tirzepatide 的 SURMOUNT-MMO 的試驗設計，這是我們在肥胖研究中的 III 期發病率和死亡率。 SURMOUNT-MMO 比較了 tirzepatide 與安慰劑相比對患有肥胖但沒有糖尿病的成年人的治療效果，並衡量了 tirzepatide 對傳統心血管事件之外的一系列廣泛結局的影響。作為我們的主要終點，我們從包括全因死亡率在內的 5 點 CV 複合材料中測量心血管事件的發生。我們還納入了關鍵的次要終點，包括傳統的 MACE 3 事件，降低了患 2 型糖尿病和腎臟不良後果的風險。

In SURMOUNT-MMO, we are studying both primary and secondary prevention of events in a broader at-risk population more representative of that seen in clinical practice. The SURMOUNT-MMO study has now initiated, and we look forward to sharing the results in the future. SURMOUNT-MMO is just the latest addition to tirzepatide's development plan where our goal is to not only demonstrate chronic weight management but also to demonstrate improvement across multiple outcomes as a result of weight loss. We're extremely confident in tirzepatide's potential to impact health outcomes of patients living with type 2 diabetes, obesity and other obesity-related metabolic outcomes.

在 SURMOUNT-MMO 中，我們正在研究更廣泛的高危人群中事件的一級和二級預防，這些人群更能代表臨床實踐中的情況。 SURMOUNT-MMO 研究現已啟動，我們期待在未來分享結果。 SURMOUNT-MMO 只是 tirzepatide 開發計劃的最新補充，我們的目標不僅是展示慢性體重管理，而且展示減肥帶來的多種結果的改善。我們對 tirzepatide 影響 2 型糖尿病、肥胖和其他肥胖相關代謝結果患者健康結果的潛力非常有信心。

Transitioning to the rest of our diabetes portfolio. We started 2 more Phase III studies for our weekly basal insulin Fc and expect to start the fifth and final registration study in the [Quint] program in the coming months. We also received FDA approval for the Tempo Smart Button, a medical device and key component of Lilly's forthcoming Tempo personalized diabetes management platform. We're excited to begin to introduce this platform to the marketplace this year.

過渡到我們的其他糖尿病產品組合。我們為每週基礎胰島素 Fc 開始了另外 2 項 III 期研究，並預計在未來幾個月內開始 [Quint] 計劃的第五次也是最後一次註冊研究。我們還獲得了 FDA 對 Tempo Smart Button 的批准，這是一種醫療設備，也是禮來即將推出的 Tempo 個性化糖尿病管理平台的關鍵組件。我們很高興今年開始將該平台引入市場。

Moving to oncology. In line with expectations previously communicated, we've now performed another interim analysis for monarchE, our adjuvant high risk early breast cancer study of Verzenio in combination with endocrine therapy for the treatment of adult patients with HR-positive, HER2-negative, node-positive early breast cancer at high risk of recurrence. The results of this analysis will be presented at the San Antonio Breast Cancer Symposium next month.

轉向腫瘤學。與之前傳達的預期一致，我們現在對 monarchE 進行了另一項中期分析，這是我們的 Verzenio 輔助高風險早期乳腺癌研究聯合內分泌治療，用於治療 HR 陽性、HER2 陰性、淋巴結-早期乳腺癌陽性，復發風險高。這項分析的結果將在下個月的聖安東尼奧乳腺癌研討會上公佈。

We're excited by what we've seen, and we look forward to sharing the data publicly. Verzenio is the only CDK4/6 inhibitor approved in the adjuvant setting, and we are enthusiastic about Verzenio's ability to substantially reduce the risk of developing incurable, life-threatening metastatic disease.

我們對我們所看到的感到興奮，我們期待著公開分享這些數據。 Verzenio 是唯一獲批用於輔助治療的 CDK4/6 抑製劑，我們對 Verzenio 能夠顯著降低發生無法治愈、危及生命的轉移性疾病風險的能力充滿熱情。

We also announced that the FDA granted accelerated approval to Retevmo for pretreated adults with locally advanced or metastatic solid tumors with a RET gene fusion regardless of tumor type. And also granted traditional approval for Retevmo in adult patients with locally advanced or metastatic non-small cell lung cancer with a RET gene fusion as detected by an FDA-approved test. We're grateful to have the opportunity to deliver meaningful clinical benefits to more patients across more tumor types with Retevmo.

我們還宣布，FDA 加速批准 Retevmo 用於治療患有局部晚期或轉移性實體瘤且具有 RET 基因融合的成人，無論腫瘤類型如何。並且還批准了 Retevmo 用於患有局部晚期或轉移性非小細胞肺癌的成年患者的傳統批准，該患者俱有經 FDA 批准的測試檢測到的 RET 基因融合。我們很高興有機會使用 Retevmo 為更多腫瘤類型的更多患者提供有意義的臨床益處。

We also began dosing patients in our fifth Phase III study for pirtobrutinib. This latest trial is a head-to-head study evaluating pirtobrutinib against ibrutinib in BTK inhibitor-naive patients with chronic lymphocytic leukemia. As a reminder, pirtobrutinib is currently under priority review at the FDA for mantle cell lymphoma previously treated with a BTK inhibitor with regulatory action expected in early 2023. We also continue to have discussions with the FDA about potentially accelerating the approval pathway for CLL in patients previously treated with a BTK inhibitor.

我們還開始在我們的第五個 pirtobrutinib III 期研究中對患者進行給藥。這項最新試驗是一項頭對頭研究，在未接受 BTK 抑製劑的慢性淋巴細胞白血病患者中評估 pirtobrutinib 與 ibrutinib 的療效。提醒一下，pirtobrutinib 目前正在 FDA 優先審查先前用 BTK 抑製劑治療的套細胞淋巴瘤，預計在 2023 年初採取監管行動。我們還繼續與 FDA 討論可能加速 CLL 患者的批准途徑以前用 BTK 抑製劑治療過。

Switching to immunology. We presented detailed week 52 results from the lebrikizumab Phase III monotherapy studies in patients with moderate to severe atopic dermatitis at 2 recent dermatology conferences. The maintenance data showed that lebrikizumab provided robust and durable skin clearance with improvements in itch, sleep and quality of life amongst patients who achieved a clinical response in the 16-week induction period.

轉向免疫學。我們在最近的 2 次皮膚病學會議上介紹了 lebrikizumab III 期單藥治療研究在中度至重度特應性皮炎患者中的詳細第 52 週結果。維持數據顯示，在 16 週誘導期達到臨床反應的患者中，lebrikizumab 提供了強大和持久的皮膚清除能力，並改善了瘙癢、睡眠和生活質量。

Notably, the results also suggested that less frequent dosing of lebrikizumab can provide similar improvements to once every 2-week dosing. Based upon the data we've collected across our trials in over 2,000 patients, we believe lebrikizumab could become a first-line biologic for treatment of moderate to severe atopic dermatitis, a disease where there's significant need to provide new options for a large and diverse patient population.

值得注意的是，結果還表明，lebrikizumab 的較少給藥頻率可以提供與每 2 週給藥一次類似的改善。根據我們在 2,000 多名患者的試驗中收集的數據，我們相信 lebrikizumab 可能成為治療中度至重度特應性皮炎的一線生物製劑，這種疾病非常需要為大型和多樣化的患者提供新的選擇。患者人群。

As part of our efforts to reach a diverse patient population, we've recently initiated an innovative clinical trial to evaluate lebrikizumab for people with skin of color who have a disproportionately higher prevalence of atopic dermatitis and often struggle with more severe forms of the disease. We have now submitted a BLA to the FDA. And Almirall, who holds rights to develop and commercialize lebrikizumab for dermatologic indications in Europe, has submitted to the EMA for authorization. We expect regulatory decisions in both the U.S. and the EU by the end of next year. Together with Almirall, we look forward to potentially bringing this important medicine to patients who suffer from this chronic disease.

作為我們努力接觸多樣化患者群體的一部分，我們最近啟動了一項創新的臨床試驗，以評估 lebrikizumab 用於有色皮膚的人，這些人的特應性皮炎患病率高得不成比例，並且經常與更嚴重的疾病形式作鬥爭。我們現在已經向 FDA 提交了 BLA。擁有在歐洲開發和商業化 lebrikizumab 用於皮膚病學適應症的權利的 Almirall 已向 EMA 提交授權。我們預計美國和歐盟將在明年年底前做出監管決定。與 Almirall 一起，我們期待著有可能將這種重要的藥物帶給患有這種慢性疾病的患者。

Shifting to our efforts in genetic medicines. You'll see that we have now advanced our ANGPTL3 siRNA to Phase II development in atherosclerotic cardiovascular disease. This is our first siRNA asset to advance to Phase II. And with this molecule, alongside our Lp(a) siRNA, where we shared proof-of-concept data last year, we're optimistic about the prospect of improving cardiovascular outcomes using our portfolio of genetic medicines.

轉向我們在基因藥物方面的努力。您會看到，我們現在已經將我們的 ANGPTL3 siRNA 推進到動脈粥樣硬化性心血管疾病的 II 期開發。這是我們第一個進入 II 期的 siRNA 資產。有了這個分子，加上我們去年分享了概念驗證數據的 Lp(a) siRNA，我們對使用我們的基因藥物組合改善心血管結果的前景持樂觀態度。

Within gene therapy, we're excited about the opportunity to help patients with fatal neurodegenerative diseases, where we're advancing our Prevail Therapeutics programs. We particularly look forward to sharing biomarker results from our progranulin gene therapy program at an upcoming scientific meeting for frontotemporal dementia.

在基因治療領域，我們很高興有機會幫助患有致命神經退行性疾病的患者，我們正在推進我們的 Prevail Therapeutics 計劃。我們特別期待在即將召開的額顳葉癡呆科學會議上分享我們的顆粒蛋白前體基因治療項目的生物標誌物結果。

Building on our gene therapy experience with Prevail, we're thrilled to welcome Akouos and their talented team who will bring a transformational gene therapy approach to treating genetically defined hearing loss. Hearing loss is an area of severe unmet need that historically has not been a focus of pharmacologic development. And we believe treatment of sensorineural hearing loss through gene therapy delivered to the inner ear is an area ripe for technologic advances for the benefit of patients.

基於我們在 Prevail 的基因治療經驗，我們很高興地歡迎 Akouos 及其才華橫溢的團隊，他們將帶來一種轉化基因治療方法來治療基因定義的聽力損失。聽力損失是一個嚴重未滿足需求的領域，歷史上一直不是藥物開發的重點。我們相信，通過傳遞到內耳的基因療法來治療感覺神經性聽力損失是一個成熟的技術進步領域，可以造福患者。

Finally, let me turn to Alzheimer's disease, where there have been a number of important developments since our last call. As a company dedicated to the fight against Alzheimer's, we were pleased to see the positive top line Phase III results for lecanemab. Following donanemab's TRAILBLAZER-ALZ study, this lecanemab study may further support the benefit of removing amyloid plaques for people with early symptomatic Alzheimer's disease.

最後，讓我談談阿爾茨海默病，自我們上次電話會議以來，該病已經出現了許多重要進展。作為一家致力於抗擊阿爾茨海默氏症的公司，我們很高興看到 lecanemab 取得了積極的 III 期臨床結果。在 donanemab 的 TRAILBLAZER-ALZ 研究之後，這項 lecanemab 研究可能進一步支持去除澱粉樣蛋白斑塊對患有早期症狀阿爾茨海默病患者的益處。

These data certainly reinforce our confidence in donanemab and the forthcoming readout from our Phase III TRAILBLAZER-ALZ 2 study, which is expected by the middle of 2023, and which, if positive, will form the basis of our application for traditional regulatory approval. In the meantime, we continue working with the FDA to seek accelerated approval in early '23 based on our TRAILBLAZER-ALZ data.

這些數據無疑增強了我們對 donanemab 的信心，以及我們的 III 期 TRAILBLAZER-ALZ 2 研究即將公佈的數據，該研究預計將在 2023 年中期進行，如果是積極的，將成為我們申請傳統監管批准的基礎。與此同時，我們繼續與 FDA 合作，根據我們的 TRAILBLAZER-ALZ 數據在 23 年初尋求加速批准。

The availability of and access to safe and effective therapies is important to slow the devastating impact on the estimated 6.5 million Americans and 35 million people worldwide living with this disease and their loved ones. While we acknowledge the hard work ahead to bring these therapies to patients in need, we are excited and we are confident in our Alzheimer's disease portfolio and the potential impact our drugs can have on patients.

安全有效療法的可用性和可及性對於減緩對估計有 650 萬美國人和全球 3500 萬患有這種疾病的人及其親人造成的破壞性影響非常重要。雖然我們承認為將這些療法帶給有需要的患者所做的艱苦工作，但我們很興奮，我們對我們的阿爾茨海默病產品組合以及我們的藥物可能對患者產生的潛在影響充滿信心。

Accordingly, we initiated TRAILRUNNER-ALZ 1, the first trial in our Phase III program for remternetug, our next-generation anti-amyloid antibody. Remternetug has demonstrated deep and rapid amyloid plaque clearance and provides the opportunity to explore flexible dosing regimens for patients.

因此，我們啟動了 TRAILRUNNER-ALZ 1，這是我們的下一代抗澱粉樣蛋白抗體 remternetug 的 III 期計劃的第一個試驗。 Remternetug 已經證明了深度和快速的澱粉樣斑塊清除，並提供了為患者探索靈活給藥方案的機會。

Finally, in TRAILBLAZER-ALZ 4, our head-to-head trial comparing donanemab to aducanumab on amyloid plaque lowering in patients with early Alzheimer's disease, we have now achieved positive results on the co-primary endpoints of amyloid lowering as expected with a consistent safety profile to previous donanemab studies. For this study, the incidence of ARIA-E in the donanemab group was 21.1%, with 2.8% of donanemab-treated patients showing symptomatic ARIA-E, suggesting the potential that rates of plaque clearance are not directly linked to rates of ARIA development. We'll share the detailed results at the upcoming CTAD meeting in late November, including the relationship between the degree of amyloid plaque removal and plasma phospho-tau as well as radiographic ARIA.

最後，在 TRAILBLAZER-ALZ 4 中，我們的頭對頭試驗比較了 donanemab 和 aducanumab 在早期阿爾茨海默病患者中降低澱粉樣斑塊的效果，我們現在在降低澱粉樣蛋白的共同主要終點上取得了積極的結果，正如預期的那樣，具有一致的以前的 donanemab 研究的安全性概況。在本研究中，多奈麥布組 ARIA-E 的發生率為 21.1%，2.8% 的多奈麥布治療患者出現症狀性 ARIA-E，這表明斑塊清除率可能與 ARIA 發展率沒有直接關係。我們將在 11 月下旬即將舉行的 CTAD 會議上分享詳細結果，包括澱粉樣斑塊去除程度與血漿 phospho-tau 以及放射學 ARIA 之間的關係。

While we focus most of our markets today on late-stage assets, you'll also notice we have a number of developments across our early-stage portfolio as shown on the slides. Across the pipeline, Q3 was another productive quarter at Lilly.

雖然我們今天的大部分市場都集中在後期資產上，但您也會注意到，我們的早期投資組合中有許多發展，如幻燈片所示。在整個管道中，第三季度是禮來公司另一個富有成效的季度。

Now I turn the call back to Dave for closing remarks.

現在我把電話轉回給戴夫以結束髮言。

Thanks, Dan. Before we go to Q&A, let me briefly sum up the progress we've made in the third quarter. We continue to grow our recently launched medicines, including Mounjaro's strong U.S. launch. At the same time, we continue to advance our pipeline, progressing towards potential launches for 4 new medicines by the end of next year while also internally and externally investing in our early-stage pipeline and discovery capabilities. With the progress we've made, we remain confident in our long-term growth prospects.

謝謝，丹。在進行問答之前，讓我簡要總結一下我們在第三季度取得的進展。我們繼續發展我們最近推出的藥物，包括 Mounjaro 在美國的強勢推出。與此同時，我們繼續推進我們的管道，爭取在明年年底前推出 4 種新藥，同時在內部和外部對我們的早期管道和發現能力進行投資。隨著我們取得的進展，我們對我們的長期增長前景仍然充滿信心。

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

現在我將把電話轉給 Joe 主持問答環節。

Thanks, Dave. (Operator Instructions) Lois, please provide the instructions for the Q&A session, and we're ready for the first caller.

謝謝，戴夫。 （操作員說明）Lois，請提供問答環節的說明，我們已為第一個來電者做好準備。

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

（操作員說明）第一個問題來自摩根大通的 Chris Schott。

I just had 2 here on Mounjaro. I guess the first is just on gross to net trends we should be thinking about from here. I think you're talking at this point about 45% access. Can you talk about where that will be trending as we look out into maybe early 2023 and when do you think you'll be at a point where the drug will have similar access to what we see with Trulicity currently?

我在 Mounjaro 上只有 2 個。我想第一個只是我們應該從這裡考慮的總體趨勢。我認為您此時正在談論大約 45% 的訪問權限。你能談談我們展望 2023 年初的趨勢嗎？你認為你什麼時候會達到這種藥物與我們目前在 Trulicity 上看到的類似的使用權的地步？

And then my second question on Mounjaro was on manufacturing capacity given what's been really an exceptional launch so far. It sounds like you're in a position to double capacity by end of '23. I guess the kind of bigger picture question I'm asking is, do you see any capacity issues that could limit uptake at all of Mounjaro as we look between now and when that additional facility comes online?

然後我關於 Mounjaro 的第二個問題是關於製造能力的，因為到目前為止真的是一次非常出色的發布。聽起來您可以在 23 年底之前將容量翻倍。我想我要問的更大的問題是，從現在到該額外設施上線時，您是否看到任何可能限制整個 Mounjaro 吸收的容量問題？

Thanks, Chris. I think maybe I'll go to Mike for both the first question on gross to net trends and access and for some commentary on manufacturing capacity. Mike?

謝謝，克里斯。我想也許我會問邁克關於總淨趨勢和訪問的第一個問題，以及關於製造能力的一些評論。麥克風？

Okay. Thanks, Chris, for the questions. I appreciate that. As we guided before launch, we recommended that you look at more revenue. It was a better indicator of our performance than net revenue.

好的。謝謝，克里斯，你的問題。我很感激。正如我們在發布前所指導的那樣，我們建議您關注更多收入。這是比淨收入更好的業績指標。

We took 2 decisions that were really focused on looking at generating long-term value for Mounjaro. First, we decided to put in place a bridging program that would bridge people who have type 2 diabetes with a low out-of-pocket cost of $25 until they achieved formulary access on their insurance. We were confident that we were going to build, and we still are confident that we're going to build good broad access for Mounjaro.

我們做出了兩個真正專注於為 Mounjaro 創造長期價值的決定。首先，我們決定實施一個橋接計劃，以 25 美元的低自付費用為 2 型糖尿病患者提供橋接服務，直到他們獲得保險的處方集。我們對我們將要建設充滿信心，而且我們仍然相信我們將為 Mounjaro 建立良好的廣泛訪問。

But we wanted to make sure that we had a bridging program in that then allowed us to be disciplined and patient as we gain access. We wanted to make sure that we look for the long term, not the short term. If you're too short term-focused, then you're going to be driven to gain access quickly and not make the right pricing decisions.

但是我們想確保我們有一個過渡計劃，然後讓我們在獲得訪問權限時能夠保持紀律和耐心。我們想確保我們著眼於長期，而不是短期。如果您過於關注短期，那麼您將被迫快速獲得訪問權限，而無法做出正確的定價決策。

So we thought the bridging program tied with the disciplined negotiation approach was the best approach. And that's the one we've taken and that's the one we've held true to during our launch.

因此，我們認為與紀律嚴明的談判方法相結合的橋接計劃是最好的方法。這就是我們所採用的，也是我們在發布期間所堅持的。

So what we'll see is net price will increase as we gain payer access. In the third quarter, we had 22% of people with commercial and Part D insurance had formulary access to Mounjaro. As of October 1, that jumped to 45%. And what we anticipate is we'll still take a disciplined, moderated approach to make sure we get the best access for the right price point. And we're still very confident that we will grow and we'll achieve broad access in the upcoming future.

因此，我們將看到，隨著我們獲得付款人訪問權限，淨價格將上漲。在第三季度，我們有 22% 的商業和 D 部分保險人可以使用 Mounjaro 的處方集。截至 10 月 1 日，這一比例躍升至 45%。我們預計，我們仍將採取嚴格、適度的方法，以確保我們以合適的價格獲得最佳訪問權限。而且我們仍然非常有信心我們會成長，並且我們將在即將到來的未來實現廣泛的訪問。

We are also adjusting our bridging program to further ensure that it's utilized for people with type 2 diabetes, which will impact new start volume but should impact net revenue. So we expect over the upcoming quarters that net price will grow for Mounjaro.

我們還在調整我們的過渡計劃，以進一步確保它用於 2 型糖尿病患者，這將影響新的開始數量，但應該會影響淨收入。因此，我們預計未來幾個季度 Mounjaro 的淨價格將會增長。

As it comes to supply, our supply chain has performed exceptionally well since launch. We're taking actions to maximize production supply for our current facilities while we ramp up our new manufacturing facilities that you referenced.

在供應方面，我們的供應鏈自推出以來表現異常出色。我們正在採取措施最大限度地提高現有設施的生產供應，同時擴大您提到的新製造設施。

The U.S. Mounjaro launch is really unprecedented with a viral nature given just tremendous patient satisfaction and the visible results that people experience that really spark many conversations with them, in the type 2 diabetes community, which then brings greater interest in the type 2 diabetes community for Mounjaro.

美國 Mounjaro 的推出確實是史無前例的，它具有病毒性質，因為患者非常滿意，人們體驗到的可見結果確實引發了與他們在 2 型糖尿病社區中的許多對話，這隨後為 2 型糖尿病社區帶來了更大的興趣蒙扎羅。

But it is a dynamic situation, given the uncertainty of competitor GLP supply and that Mounjaro's patient prescription abandonment, long-term adherence and dose titration rates haven't yet reached steady-state, which are all important forecasting assumptions.

但鑑於競爭對手 GLP 供應的不確定性以及 Mounjaro 的患者處方放棄、長期依從性和劑量滴定率尚未達到穩定狀態，這是一個動態的情況，這些都是重要的預測假設。

So given the dynamic nature of this, it's reasonable to assume that weekly production forecast won't perfectly align with weekly demand each week. So this will produce some intermittent delays in meeting wholesale orders for some dosing strengths as we ramp up our supply chain. If this happens, our teams will work hard to avoid or minimize any short-term impact for people living with type 2 diabetes.

因此，鑑於這種情況的動態性，可以合理地假設每週的產量預測不會與每週的每週需求完全一致。因此，隨著我們擴大供應鏈，這將在滿足某些劑量強度的批發訂單方面產生一些間歇性延遲。如果發生這種情況，我們的團隊將努力避免或盡量減少對 2 型糖尿病患者的任何短期影響。

But stepping back and taking a look at the longer-term picture, we're in a great position. Mounjaro's launch is going extremely well because patient experiences have been tremendous, and they have a high interest in the product profile. We expect Mounjaro's launch has fueled significant incretin market growth, which I think just gives us more confidence in the future. And we had the foresight to initiate significant manufacturing capacity expansion before Mounjaro even launched because we saw the potential of the product. So we're in a very good long-term position with Mounjaro.

但是退後一步，看看長期的情況，我們處於一個很好的位置。 Mounjaro 的推出非常順利，因為患者體驗非常好，而且他們對產品簡介非常感興趣。我們預計 Mounjaro 的推出推動了腸促胰島素市場的顯著增長，我認為這讓我們對未來更有信心。我們有先見之明，在 Mounjaro 推出之前就啟動了顯著的製造能力擴張，因為我們看到了產品的潛力。因此，我們在 Mounjaro 處於非常有利的長期地位。

The next question is from Terence Flynn from Morgan Stanley.

下一個問題來自摩根士丹利的 Terence Flynn。

Maybe 2 follow-ups for me. So just on the manufacturing side. I mean, is that kind of supply challenges you're going to run into kind of expected through the first half of the year? I'm just wondering if there's any way you can bring North Carolina on board any sooner. I know you've guided to year-end, but just maybe help us think about anything you can do to kind of bring that online sooner.

也許對我來說有 2 個後續行動。所以只是在製造方面。我的意思是，你會在今年上半年遇到這種供應挑戰嗎？我只是想知道是否有任何方法可以讓北卡羅來納州盡快加入。我知道你已經指導到年底了，但也許可以幫助我們考慮一下你可以做些什麼來更快地把它上線。

And then the bridging program, Mike, you mentioned you made some changes there. So the percentage of patients not with type 2 diabetes will may be different on the forward. Can you tell us what that represents currently and how we should think about that change to volume on the forward?

然後是橋接程序，邁克，你提到你在那裡做了一些改變。因此，未來非 2 型糖尿病患者的百分比可能會有所不同。您能告訴我們目前這代表什麼，以及我們應該如何看待前鋒交易量的變化？

Thanks, Terence. Mike?

謝謝，特倫斯。麥克風？

Yes. On manufacturing supply, I'll reinforce that our manufacturing supply and teammates have delivered exceptional results, and they continue to look for every way to maximize our production supply. They have all hands on deck to get the Research Triangle Park facility online as soon as possible. And as soon as that facility is available, we'll make good use of that supply.

是的。在製造供應方面，我將強調我們的製造供應和隊友已經取得了非凡的成果，他們繼續尋找各種方法來最大化我們的生產供應。他們全力以赴，盡快讓三角研究園設施上線。一旦該設施可用，我們將充分利用該供應。

So we're confident in our ability for our manufacturing personnel and our leadership there. And as I said before, we're very confident in the long-term potential of tirzepatide.

因此，我們對我們的製造人員和我們在那裡的領導能力充滿信心。正如我之前所說，我們對 tirzepatide 的長期潛力非常有信心。

With the bridging program, I think your question was more around kind of off-label use of Mounjaro and how much it was. As you know, Mounjaro was approved in the U.S. for patients with type 2 diabetes, and we have just excellent processes in place to ensure that all promotional activities are in line with our approved label.

對於橋接計劃，我認為您的問題更多是關於 Mounjaro 的標籤外使用以及它是多少。如您所知，Mounjaro 在美國被批准用於 2 型糖尿病患者，我們剛剛制定了出色的流程，以確保所有促銷活動都符合我們批准的標籤。

We're pleased with our disciplined on-label promotional execution. The launch of Mounjaro has been very disciplined and in line with everything that we wanted. So we've been encouraged by both patients and physicians prescribing experiences, and this has driven a very high interest in Mounjaro.

我們對我們嚴格的標籤促銷執行感到滿意。 Mounjaro 的推出非常有紀律，符合我們想要的一切。因此，我們受到患者和醫生處方經驗的鼓舞，這激發了對 Mounjaro 的濃厚興趣。

We haven't -- we don't have perfect data to suggest what diagnosis a patient has. The best data that we have is to look at the -- whether those individuals who are starting Mounjaro, whether they have previously been on a diabetes medication or not. Given that our promotion is focused solely on type 2 diabetes, we would expect to see the majority of people use Mounjaro for type 2 diabetes, and that's what we've seen.

我們沒有——我們沒有完美的數據來建議患者的診斷。我們擁有的最好的數據是看看那些開始 Mounjaro 的人，他們以前是否服用過糖尿病藥物。鑑於我們的促銷活動僅針對 2 型糖尿病，我們希望看到大多數人使用 Mounjaro 治療 2 型糖尿病，這就是我們所看到的。

While we see fluctuation from week to week in the third quarter, we saw about 2/3 of new patients starting Mounjaro with a history of type 2 diabetes medications. For the remaining 1/3 of patients who are classified as naive to treatment -- diabetes treatments, these individuals could either be newly diagnosed type 2 diabetes patients or individuals who haven't yet been diagnosed with type 2 diabetes.

雖然我們看到第三季度每週都有波動，但我們看到大約 2/3 的新患者開始使用 Mounjaro 有 2 型糖尿病藥物的歷史。對於其餘 1/3 被歸類為未接受過治療的患者（糖尿病治療），這些人可能是新診斷的 2 型糖尿病患者或尚未被診斷出患有 2 型糖尿病的人。

The next question is from Umer Raffat from Evercore.

下一個問題來自 Evercore 的 Umer Raffat。

Maybe a quick one -- a quick couple of questions on Mounjaro: a, if you could speak to the inventory contribution to the third quarter U.S. sales; and b, I was just trying to compare Mounjaro gross to net and the dollars per Rx early into the launch and compared versus how Trulicity did early into the launch. And I think what stands out is the revenues per Rx were several fold higher from Trulicity. Perhaps if you could speak to any specific differences in the types and extent of patient support you did early in Trulicity launch versus what you're doing in Mounjaro. Clearly, the volumes majorly, majorly surpass what Trulicity did early on.

也許是一個快速的問題——關於 Mounjaro 的幾個快速問題：a，如果你能談談庫存對第三季度美國銷售的貢獻； b，我只是想在發布初期比較 Mounjaro 的總收入和淨值以及每 Rx 的美元，並與 Trulicity 在發布初期的表現進行比較。我認為最突出的是每 Rx 的收入比 Trulicity 高出幾倍。也許如果您能說出您在 Trulicity 發布早期所做的患者支持的類型和程度與您在 Mounjaro 所做的任何具體差異。顯然，數量大大超過了 Trulicity 早期所做的。

Thanks, Umer. So Mike, go back to you on both questions. First one on inventory contribution to Q2 sales, and then the second on the gross to net and how that would compare versus what we saw with Trulicity.

謝謝，烏默爾。所以邁克，在這兩個問題上都回复你。第一個是關於庫存對第二季度銷售的貢獻，然後是第二個是總淨額，以及與我們在 Trulicity 中看到的相比如何。

Okay. Good question. Inventory contributions to Q3 sales was 40%. But I also note that as soon as a [product -- ship] our product, we accrue for rebates and discounts, whether that product is used to supply patient demand in the pharmacy or whether that's used in the channel for inventory.

好的。好問題。庫存對第三季度銷售額的貢獻為 40%。但我也注意到，一旦[產品——發貨]我們的產品，我們就會獲得回扣和折扣，無論該產品是用於滿足藥房的患者需求，還是用於庫存渠道。

As it comes to gross to net, the big change is, if you look at the Trulicity launch versus the Mounjaro launch is we did not have a bridging program at the launch of Trulicity like we do for Mounjaro.

就總淨額而言，最大的變化是，如果你看一下 Trulicity 的發布與 Mounjaro 的發布，我們在 Trulicity 發佈時沒有像 Mounjaro 那樣的過渡計劃。

The next question is from Steve Scala from Cowen.

下一個問題來自 Cowen 的 Steve Scala。

Why does Lilly think FDA is requiring it to submit results from SURMOUNT-2 for the tirzepatide obesity filing when that study would not seem particularly relevant given that it is in diabetics, does not select for obesity and is smaller than SURMOUNT-1? And given that the FDA request seems of tenuous value, could it be relaxed perhaps on an interim look at SURMOUNT-2? So that's the first question.

為什麼禮來公司認為 FDA 要求它提交 SURMOUNT-2 的結果以提交 tirzepatide 肥胖申報，因為該研究似乎並不特別相關，因為它是在糖尿病患者中，不選擇肥胖並且小於 SURMOUNT-1？鑑於 FDA 的要求似乎價值微乎其微，是否可以在對 SURMOUNT-2 進行臨時研究時放寬它？所以這是第一個問題。

Second, why did Lilly sell co-promotion rights to Mounjaro in Japan when it is, I believe, Lilly's second largest market, Lilly has a large footprint there presumably, Mounjaro is a critical long-term driver to Lilly, and do so for only $86 million? Granted Lilly has done this before, such as selling rights to Cialis in China, but that was at one -- at a point when Cialis was in steep decline, whereas Mounjaro is your future.

其次，為什麼禮來公司在日本向 Mounjaro 出售聯合推廣權，而我相信，禮來公司是禮來公司的第二大市場，禮來公司大概在日本有很大的足跡，Mounjaro 是禮來公司的關鍵長期驅動力，並且這樣做只是為了8600萬美元？誠然禮來公司以前也這樣做過，例如在中國向 Cialis 出售權利，但那是在一個時刻——在 Cialis 急劇下降的時候，而 Mounjaro 是你的未來。

Thanks, Steve. So first, for the question about the FDA and submission for tirzepatide for obesity, we'll go to Dan. And then your second question around the collaboration agreement in Japan, we'll go to Ilya. So Dan?

謝謝，史蒂夫。因此，首先，關於 FDA 和提交用於肥胖的替西帕肽的問題，我們將去找丹。然後你關於日本合作協議的第二個問題，我們會去伊利亞。那麼丹?

Yes. Thanks, Steve, for the question on SURMOUNT-2 here and FDA requirements. Maybe I'll just start off by relieving any worries that there's any specific concerns with the data or safety or anything like that. We don't see anything such as that driving FDA concerns.

是的。謝謝史蒂夫，關於這裡的 SURMOUNT-2 和 FDA 要求的問題。也許我會首先消除對數據或安全性或類似問題的任何擔憂。我們沒有看到任何諸如推動 FDA 關注的事情。

I think the FDA discussion around having 2 trials is just to be consistent with FDA guidance for adequate and well-controlled studies in chronic weight management that for that indication, having multiple studies in a population with obesity with primary endpoints defined as per the guidance on thresholds of weight loss is the requirement. And that's the requirement, being [held to have] 2 studies.

我認為 FDA 關於進行 2 項試驗的討論只是為了符合 FDA 對慢性體重管理進行充分和控制良好的研究的指導，對於該適應症，在肥胖人群中進行多項研究，主要終點根據指南定義減肥的門檻是要求。這就是要求，被[持有] 2 項研究。

Thanks, Dan. Ilya, do you want to take the question around the Japan tirzepatide?

謝謝，丹。 Ilya，你想回答關於日本 tirzepatide 的問題嗎？

Yes. Steve, thank you for the question. You're right, Japan is a critical market. Just to clarify, the $86 million that we recognized for revenue and payment from Mitsubishi Tanabe was for an upfront payment for collaboration, which is consistent with partnerships we've had in Japan for a number of our growth brands. Like Trulicity, like Emgality, we've had success in having strategic partnerships with local Japanese companies to successfully commercialize our innovative treatments. We believe that this partnership will allow us to maximize the value of tirzepatide in Japan. And Mitsubishi Tanabe does have significant scale and experience in diabetes, and together, we will collaborate. And just to clarify, we will preserve the economics -- ongoing economics for the launch and sales of Mounjaro in Japan for Lilly.

是的。史蒂夫，謝謝你的問題。沒錯，日本是一個關鍵市場。澄清一下，我們從 Mitsubishi Tanabe 確認的 8600 萬美元的收入和付款是用於合作的預付款，這與我們在日本為我們的一些成長品牌建立的合作夥伴關係是一致的。像 Trulicity 和 Emgality 一樣，我們成功地與日本當地公司建立了戰略合作夥伴關係，從而成功地將我們的創新療法商業化。我們相信，這種夥伴關係將使我們能夠最大限度地發揮 tirzepatide 在日本的價值。田邊三菱在糖尿病領域確實擁有顯著的規模和經驗，我們將攜手合作。澄清一下，我們將保留經濟學——禮來在日本推出和銷售 Mounjaro 的持續經濟學。

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

下一個問題來自美國銀行的 Geoff Meacham。

Thanks for the question. Mike, you mentioned a low switch rate to Mounjaro from Trulicity, but what was the driver of sequential trends for Trulicity? And maybe how do you see cannibalization playing out in the next few years?

謝謝你的問題。 Mike，您提到了從 Trulicity 到 Mounjaro 的低轉換率，但 Trulicity 連續趨勢的驅動因素是什麼？也許你如何看待未來幾年的自相殘殺？

And then the second question for Dan, on tirzepatide and obesity, you guys added the MMO study, but there are a lot of other additional indications beyond what you guys have talked about where obesity plays a role like a few coronary syndromes or other broad cardio indications come to mind. So how do you guys plan on prioritizing the clinical investments from here for tirzepatide? Like what's the math that goes into that?

然後是丹的第二個問題，關於替西帕肽和肥胖，你們添加了 MMO 研究，但是除了你們所討論的肥胖在某些冠狀動脈綜合徵或其他廣泛的心臟疾病中發揮作用之外，還有很多其他的跡象跡象浮現在腦海。那麼你們打算如何優先考慮從這裡開始對 tirzepatide 的臨床投資呢？就像其中的數學原理是什麼？

Thanks, Geoff. So Mike, we'll go to you for the question around sequential trends and what we expect -- might expect in terms of ongoing switch rates, and then Dan, we'll go to you for prioritization of tirzepatide development plans. Mike?

謝謝，傑夫。所以邁克，我們將向您詢問有關連續趨勢的問題以及我們的預期 - 可能會預期持續的轉換率，然後是丹，我們將向您詢問 tirzepatide 開發計劃的優先級。麥克風？

Yes. What you typically see is actually the switching for a new product into an incretin class is typically the switch rates -- people switching from another incretin to the launch incretin, those rates will actually go down over time. And so that's what I would anticipate. The real opportunity here is to grow the market and make sure of that before being proactive to treat type 2 diabetes.

是的。您通常看到的實際上是將新產品切換到腸促胰島素類通常是切換率——人們從另一種腸促胰島素切換到啟動腸促胰島素，這些率實際上會隨著時間的推移而下降。這就是我所期望的。這裡真正的機會是在積極治療 2 型糖尿病之前擴大市場並確保這一點。

Thanks, Mike. Okay, Dan?

謝謝，邁克。好嗎，丹？

Geoff, thanks for the question on future indications for tirzepatide. There are many that we can consider. As you point out, weight loss and restoration of sort of normal metabolism, which we think may be possible with tirzepatide, is going to have benefits in a lot of metabolic- and obesity-related diseases. So how do we pick which ones to pursue and when?

傑夫，感謝關於替西帕肽未來適應症的問題。我們可以考慮的有很多。正如您所指出的，減肥和恢復某種正常的新陳代謝（我們認為使用替西帕肽可能是可能的）將對許多與代謝和肥胖相關的疾病有益。那麼我們如何選擇追求哪些以及何時追求？

I think initially, our thinking has been around generating a body of data that shows that a drug such as tirzepatide when driving weight loss can lead to downstream health benefits. So that's what drives the MMO study. We have a heart failure study, a sleep apnea study that are all ongoing.

我認為最初，我們的想法一直圍繞著生成大量數據，這些數據表明，像替西帕肽這樣的藥物在減輕體重時可以帶來下游的健康益處。這就是推動 MMO 研究的原因。我們正在進行心力衰竭研究和睡眠呼吸暫停研究。

When we think about adding more, sort of where can we see improvements in that medical understanding of the dangers of obesity and the benefits of weight loss and restoration of normal metabolism. That's how we think about it rather than how big is this patient segment or how big is the next patient segment, noting that almost all of those patient segments will already have obesity as an underlying disease, which we expect to have indicated next year, as I commented earlier.

當我們考慮添加更多時，我們可以在哪裡看到對肥胖危險的醫學理解以及減肥和恢復正常新陳代謝的好處的改進。這就是我們的想法，而不是這個患者群體有多大或下一個患者群體有多大，並指出幾乎所有這些患者群體都已經將肥胖作為潛在疾病，我們預計明年會指出這一點，因為我之前評論過。

Finally, I think one more consideration here, Geoff, for us is we see fighting obesity as a long-term goal for Eli Lilly and Company. And so there'll be multiple generations of drugs here, we hope. And we'll have lots of opportunities to contribute to our medical understanding of weight loss.

最後，傑夫，我認為這裡的另一個考慮因素是，我們將對抗肥胖視為禮來公司的長期目標。所以我們希望這裡會有多代藥物。我們將有很多機會為我們對減肥的醫學理解做出貢獻。

The next question is from Mohit Bansal from Wells Fargo.

下一個問題來自富國銀行的 Mohit Bansal。

So maybe one question on Mounjaro growth in obesity. So when you talk about 100 million patient population, which are obese, not diabetic, I see you're talking about primary prevention. But if you look at the current trials, they are more of secondary prevention type of setting. So the question is how important is getting a primary prevention trial done to get to the broadest patient population in obesity market possible at this point?

因此，也許是關於 Mounjaro 肥胖增長的一個問題。因此，當您談到 1 億肥胖患者而非糖尿病患者時，我看到您是在談論初級預防。但如果你看看目前的試驗，它們更多的是二級預防類型的設置。所以問題是，在這一點上，進行初級預防試驗以覆蓋肥胖市場上最廣泛的患者群體有多重要？

Thanks, Mohit, for the question. You were a little bit echoey there, but I think we got the gist around the patient population for obesity and how to maximize that opportunity. Mike, do you want to take that?

謝謝，莫希特的問題。你在那裡有點迴聲，但我認為我們掌握了肥胖患者群體的要點，以及如何最大限度地利用這一機會。邁克，你想拿那個嗎？

Yes, I'm happy to answer that question. Actually, with obesity, it's actually kind of counter to what typically happens with the product. Typically, you get it out, it has a finite patient segmentation. You try to expand that with additional indications. Actually, with obesity, you're going to have the broadest indication for people who either have a BMI of 27 with a risk factor or a BMI over 30, which is a massive population in the U.S. and globally.

是的，我很高興回答這個問題。實際上，對於肥胖，它實際上與產品通常發生的情況相反。通常，你把它拿出來，它有一個有限的病人分割。您嘗試使用其他指示來擴展它。實際上，對於肥胖症，對於 BMI 為 27 且有風險因素或 BMI 超過 30 的人（在美國和全球都是一個龐大的人口），您將獲得最廣泛的適應症。

And so the additions of our trials aren't necessarily to expand the patient population, but is to demonstrate that proactively treating obesity will improve health outcomes in order to drive physicians to write and payers to give access for the product.

因此，我們增加試驗並不一定是為了擴大患者人數，而是為了證明積極治療肥胖症將改善健康結果，以促使醫生寫作和付款人提供產品使用權。

The next question is from Seamus Fernandez from Guggenheim.

下一個問題來自古根海姆的 Seamus Fernandez。

So a couple of quick ones. So with regard to the North Carolina facility expanding manufacturing capacity, in terms of API versus the actual pens and fill-finish manufacturing, can you just update us on what really is the potential expansion of manufacturing there? It's my understanding that the potential bottleneck is going to be more related to the pen manufacturing.

所以有幾個快速的。因此，關於北卡羅來納州工廠擴大製造能力，就 API 與實際筆和填充完成製造而言，您能否向我們介紹一下那裡真正的潛在製造擴張？據我了解，潛在的瓶頸將更多地與鋼筆製造有關。

And it's my understanding also that this is largely the Trulicity pen and the Trulicity pen is going to be the main manufacturing point for pretty much all of your biologic capacity as well as for Trulicity. So just trying to get a better understanding of that.

我的理解也是，這主要是 Trulicity 筆，而 Trulicity 筆將成為您幾乎所有生物能力以及 Trulicity 的主要製造點。所以只是試圖更好地理解這一點。

And then second, just on the insulin. There are a number of questions around the change to the penny rule and how Lilly and competitor, Novo, are going to manage through that as many of the insulins could actually be sort of paying the Medicaid fees for the benefit of actually providing insulins. So just trying to get a better understanding of how Lilly hopes to manage that outcome, in particular. It seems wildly unfair to the industry.

其次，就在胰島素上。圍繞一分錢規則的變化以及禮來和競爭對手 Novo 將如何解決這一問題存在許多問題，因為許多胰島素實際上可能是為了實際提供胰島素而支付醫療補助費用。所以只是想更好地了解禮來希望如何管理這一結果，特別是。這似乎對這個行業非常不公平。

Thanks, Seamus. So I think for the first question on the kind of North Carolina manufacturing facility dynamics, I'll hand over to Dave. I mean, Dave, if you want to comment also on the insulin, I think he's referring to the AMP cap dynamics.

謝謝，西莫。所以我認為關於北卡羅來納州製造設施動態的第一個問題，我將交給戴夫。我的意思是，戴夫，如果你也想對胰島素發表評論，我認為他指的是 AMP 上限動態。

I can. And Mike, jump in if I get that wrong. So just to step back on capacity, we did make some comments today related to this. And we've taken actions in the quarter to slow demand internationally on Trulicity, primarily because of the constraints by a competitor, which have shifted demand to Trulicity internationally. Should that happen domestically, of course, that will -- I think we're just trying to give a fair balance to say that, that would be an increase in demand we'd have to manage too as well.

我可以。邁克，如果我弄錯了，請加入。因此，為了降低容量，我們今天確實發表了一些與此相關的評論。我們在本季度已採取行動減緩國際對 Trulicity 的需求，主要是因為競爭對手的限制，這已將國際需求轉移到 Trulicity。當然，如果這種情況發生在國內，那將——我認為我們只是試圖給出一個公平的平衡來說明，這將是我們也必須管理的需求增加。

But we are producing above our plans right now. We see that continuing. And the next step-up, Seamus, that we expect in capacity will be North Carolina, which will happen towards the end of next year. Just for clarity, there's actually 2 sites in North Carolina. One we announced in 2020 and one more recently down the road in Concord near Charlotte. That second facility will also come online beginning in '24 with some capacity and really '25 more fully.

但我們現在的生產超出了我們的計劃。我們看到這種情況仍在繼續。下一個升級，Seamus，我們預計容量將是北卡羅來納州，這將發生在明年年底。為清楚起見，北卡羅來納州實際上有 2 個站點。我們在 2020 年宣布了一項，最近在夏洛特附近的康科德宣布了一項。第二個設施也將從 24 年開始以一定的容量上線，並且真正在 25 年更充分。

So the company has taken some pretty aggressive investment steps, and those steps in North Carolina are focused on what we'll call the parental filling and the drug finishing process, which is the device that is used for Trulicity, but also Mounjaro.

因此，該公司採取了一些相當激進的投資步驟，而在北卡羅來納州的這些步驟主要集中在我們所說的父母灌裝和藥物整理過程，這是用於 Trulicity 和 Mounjaro 的設備。

We take a platform approach. So that device is also used for other Lilly biologics. And it gives us flexibility to match supply and demand more agilely. Although Mike's comments were well placed earlier that it's not perfect, like inside of 90 days, we can't perfectly match every SKU of demand to every SKU produced. But it does give us a lot of agility.

我們採用平台方式。因此，該設備也用於其他禮來生物製劑。它使我們能夠靈活地更靈活地匹配供需。儘管之前 Mike 的評論很好地表明它並不完美，比如在 90 天內，我們無法將每個需求 SKU 與生產的每個 SKU 完美匹配。但它確實給了我們很大的靈活性。

Those 2 sites in North Carolina, I'll point out, I think as Anat said, are huge. So the first one will literally double our global capacity when it's online, and the second site is a similar size. So we've taken some big CapEx decisions, and it looks well placed given the early uptick in Mounjaro, which looks quite substantial.

北卡羅來納州的那兩個站點，我要指出，我認為正如 Anat 所說，它們是巨大的。因此，第一個站點在線時實際上將使我們的全球容量翻倍，而第二個站點的大小相似。因此，我們做出了一些重大的資本支出決定，考慮到 Mounjaro 的早期上漲，它看起來很合適，看起來相當可觀。

Those do not speak to the API side. API is a different supply chain. We've also taken actions to expand that capacity. It's currently not the bottleneck and is not expected to be the bottleneck, which is the peptide synthesis process we use.

這些與 API 方面無關。 API 是一個不同的供應鏈。我們還採取了行動來擴大這種能力。目前不是瓶頸，預計也不會是瓶頸，就是我們使用的肽合成工藝。

Of course, big caveat around all this is, of course, things can go wrong. Regulatory approvals are required to bring the new sites online in an on-time fashion, but that's our current outlook. And as Mike said, long term, we're extremely confident we can supply a massive volume of Trulicity and Mounjaro. But these step-ups do take a little bit of time. And should we have a lapse in competitor supply, that will challenge our ability to meet demand. I think that's the main message from today.

當然，關於這一切的重大警告是，當然，事情可能會出錯。需要獲得監管部門的批准才能使新網站按時上線，但這是我們目前的展望。正如邁克所說，從長遠來看，我們非常有信心能夠供應大量的 Trulicity 和 Mounjaro。但這些升級確實需要一點時間。如果我們在競爭對手的供應方面出現失誤，那將挑戰我們滿足需求的能力。我認為這是今天的主要信息。

As it relates to AMP cap, you're right that beginning in January of '24, the cap on payments or rebates to Medicaid programs for medications that have a CPI penalty that pushes them above 100% rebate will be lifted, and we will be required to pay states to use our product in that situation. We have not announced our plans to deal with that, although we're formulating plans to deal with that.

由於它與 AMP 上限有關，您是對的，從 24 年 1 月開始，對於那些因 CPI 罰款將其推高至 100% 回扣以上的藥物，向 Medicaid 計劃支付或回扣的上限將被取消，我們將在這種情況下，需要向各州付費才能使用我們的產品。我們還沒有宣布我們的計劃來解決這個問題，儘管我們正在製定計劃來解決這個問題。

And of course, the best thing to do is keep inventing new things, which reset that calculation. And as you know, we've got a Phase III program for weekly insulin, and we're progressing efforts on glucose-sensing insulin. We've got, I think, an exciting new approval on Connected Care as well. So all those efforts, I think, are the long-term approach. Tactically, we'll manage through that event at the end of '23, early '24.

當然，最好的辦法是不斷發明新事物，從而重新計算。如你所知，我們有一個每週一次的胰島素 III 期計劃，我們正在努力開發葡萄糖感應胰島素。我認為，我們在 Connected Care 上也獲得了令人興奮的新批准。因此，我認為所有這些努力都是長期的方法。從戰術上講，我們將在 23 年底、24 年初完成該事件。

The next question is from Chris Shibutani from Goldman Sachs.

下一個問題來自高盛的 Chris Shibutani。

Two questions. One on the obesity opportunity for tirzepatide and the regulatory requirements there. SURMOUNT-3 and 4, I believe, are expected to complete also in the first half of next year. Should we be clear in terms of not anticipating that data from those studies are required or that you'll be planning to submit those to the FDA? And if you were to, would that have any potential implications on the time line for potential approval and processing?

兩個問題。一個關於 tirzepatide 的肥胖機會和那裡的監管要求。我相信，SURMOUNT-3 和 4 預計也將在明年上半年完成。我們是否應該明確表示不需要來自這些研究的數據，或者您將計劃將這些數據提交給 FDA？如果您要這樣做，這會對潛在的批准和處理的時間線產生任何潛在影響嗎？

Second, you highlighted some data on Verzenio that we're going to see at SABCS. Can you just maybe contextualize for us what you believe might be the potential impact in terms of the adjuvant metastatic split? And anything in terms of how that might influence the trajectory of Verzenio from a revenue standpoint once we see that data?

其次，您強調了我們將在 SABCS 上看到的有關 Verzenio 的一些數據。您能否為我們解釋一下您認為在輔助轉移分裂方面可能產生的潛在影響？一旦我們看到這些數據，從收入的角度來看，這可能會如何影響 Verzenio 的發展軌跡？

Thanks, Chris. Okay. For the first question on tirzepatide, obesity and the regulatory requirements, SURMOUNT-3 and 4, we'll go to Dan, and then we'll go to Jake for the Verzenio San Antonio Breast Conference, maybe preview.

謝謝，克里斯。好的。對於關於 tirzepatide、肥胖和監管要求的第一個問題，SURMOUNT-3 和 4，我們會去找 Dan，然後我們會去找 Jake 參加 Verzenio San Antonio 乳房會議，也許是預覽。

Thanks, Chris. Our understanding is that we'll submit based on SURMOUNT-1 and SURMOUNT-2, as we said, and we don't anticipate needing SURMOUNT-3 and 4 for that submission. So no implications to time line from those study readouts.

謝謝，克里斯。我們的理解是，正如我們所說，我們將根據 SURMOUNT-1 和 SURMOUNT-2 提交，並且我們預計該提交不需要 SURMOUNT-3 和 4。因此，這些研究讀數對時間線沒有影響。

Jake, do you want to jump in on Verzenio?

傑克，你想加入 Verzenio 嗎？

Yes, sure. So as Dan mentioned in the prepared remarks, we conducted a preplanned interim analysis of monarchE as we had talked about earlier in the year that we were going to do that. So of course, we looked at all of the endpoints, IDFS, DRFS and overall survival. We'll be presenting those at San Antonio. Really pleased with what we've seen across the study in both the ITT population cohort 1 as well as the currently labeled indication.

是的，當然。因此，正如 Dan 在準備好的評論中提到的那樣，我們對 monarchE 進行了預先計劃的中期分析，正如我們在今年早些時候談到的那樣，我們將這樣做。因此，當然，我們查看了所有端點、IDFS、DRFS 和總體生存率。我們將在聖安東尼奧展示這些。對我們在 ITT 人群隊列 1 和當前標記的適應症的研究中看到的結果感到非常滿意。

I think there's 2 components to think about here. One is, how do the data continue to evolve with increased follow-up? And the second is, how does the new analysis look as it relates to potentially expanding our labeled indication over time? And obviously, I want to be careful about previewing the data themselves, but I think those are the 2 questions that you ought to think about as you see the data in December.

我認為這裡有兩個組件需要考慮。一是，隨著後續行動的增加，數據如何繼續發展？第二個是，隨著時間的推移，新的分析與潛在地擴展我們的標記適應症有何關係？顯然，我想謹慎預覽數據本身，但我認為這是你在 12 月份看到數據時應該考慮的兩個問題。

Next question is from Colin Bristow from UBS.

下一個問題來自瑞銀的 Colin Bristow。

Congrats on the quarter. Two from my side, first on obesity. There's been quite a bit of discussion around Amgen's upcoming 133 data. And so could you give us your thoughts on GIP agonism versus antagonism? And just on your development side, could you just remind us when we next get updates on GGG and mazdutide?

祝賀本季度。我這邊有兩個，首先是肥胖。圍繞 Amgen 即將發布的 133 數據進行了大量討論。那麼你能告訴我們你對 GIP 激動與對抗的看法嗎？就您的開發方面而言，您能否在我們下次獲得 GGG 和 mazdutide 的更新時提醒我們？

And then on the Alzheimer's side, I'm just wondering on donanemab, was any part of your decision to pursue a discrete dosing strategy with regards to stopping when you achieve amyloid negativity? Was any part of that related to antidrug antibodies? I'm just thinking about this, given there's some data suggesting redosing or maintenance dosing may actually be beneficial.

然後在阿爾茨海默氏症方面，我只是想知道關於 donanemab，當您實現澱粉樣蛋白陰性時，您是否決定採用離散劑量策略來停止？其中有任何部分與抗藥抗體有關嗎？我只是在考慮這一點，因為有一些數據表明重新給藥或維持給藥實際上可能是有益的。

Thanks, Colin. We'll go to Dan on both questions. First one around obesity, Amgen's data and then the second one around Alzheimer's and discrete dosing related to antidrug antibodies.

謝謝，科林。我們將就這兩個問題去找丹。第一個圍繞肥胖，安進的數據，然後第二個圍繞阿爾茨海默氏症和與抗藥抗體相關的離散劑量。

Yes. Thanks. Starting with how we think about obesity and incretins in general. As much as possible here, our strategy has been to mimic the body's own response to food. So incretins are hormones submitted by -- secreted rather by your gastrointestinal tract in response to eating, which then lead to feelings of satiety and increased calorie expenditure and decreased food intake. That's how they work, and GIP is one of the major incretins. So it made sense to pursue a strategy of agonism of that hormone. And probably we'll wait and see Amgen's data to understand if antagonism could also have a surprising effect different than the biological effect of incretins normally in humans.

是的。謝謝。從我們一般如何看待肥胖和腸促胰島素開始。在這裡，我們的策略是盡可能地模仿身體對食物的反應。所以腸促胰島素是由你的胃腸道在進食時分泌的激素，它會導致飽腹感、卡路里消耗增加和食物攝入減少。這就是它們的工作方式，而 GIP 是主要的腸促胰島素之一。因此，追求這種激素的激動策略是有意義的。也許我們會等著看安進的數據，以了解拮抗作用是否也會產生不同於人類正常腸促胰島素生物學效應的驚人效應。

With respect to GGG and mazdutide, I think GGG is our next-generation incretin that's further ahead in development. We've previously communicated that we expect to have internal Phase II data yet this year and use that data to make a decision whether this proceeds to Phase III or not, in which case, we might wait for mazdutide data. That thinking is still consistent and on track for yet this year.

關於 GGG 和 mazdutide，我認為 GGG 是我們的下一代腸促胰島素，在開發方面更領先。我們之前曾表示，我們預計今年會有內部 II 期數據，並使用該數據來決定是否進入 III 期，在這種情況下，我們可能會等待 mazdutide 數據。這種想法仍然是一致的，並且在今年仍在進行中。

The second line of questioning here was around donanemab discrete dosing strategy, and you're referring here to the notion that we pioneered that once plaques are clear, you can stop taking a plaque-clearing antibody. That was based on our understanding of the biology, nothing to do with antidrug antibodies.

這裡的第二個問題是圍繞 donanemab 離散給藥策略，您在這裡指的是我們開創的概念，即一旦斑塊清除，您就可以停止服用清除斑塊的抗體。那是基於我們對生物學的理解，與抗藥抗體無關。

But certainly, we see it as a benefit for patients to not have to continue to take a drug in the absence of having the target or the disease in their brain that's still ongoing. It's pretty specific idea to donanemab, remternetug and antibodies that are specific to plaques because once the plaques are gone, there's nothing for the antibodies to do.

但可以肯定的是，我們認為患者在沒有靶標或大腦中仍在持續的疾病的情況下不必繼續服用藥物是一種好處。對於斑塊特異性的 donanemab、remternetug 和抗體來說，這是一個非常具體的想法，因為一旦斑塊消失，抗體就無能為力了。

Our own data that we've shared show that there is no reversion really of adverse biomarkers in patients who've come off therapy. So so far, the data that we have in hand, though it's still early, supports cessation of dosing as appropriate. We'll look to TRAILBLAZER-2 to confirm that hypothesis.

我們自己分享的數據表明，在停止治療的患者中，不良生物標誌物確實沒有逆轉。到目前為止，我們手頭的數據雖然還為時過早，但支持酌情停止給藥。我們將期待 TRAILBLAZER-2 來證實這一假設。

The next question is from David Risinger from SVB Securities.

下一個問題來自 SVB 證券的 David Risinger。

I guess first, although there was 22% coverage in the U.S. in the third quarter, that didn't fully translate into net revenue. So could you provide some more color on why that was the case? Was it because formulary access at the national level may not immediately translate to paid Rx for certain downstream customers of payers because additional negotiations may be required? I thought that might be a factor, and this will help us better understand how to think about the 45% coverage that you have as of October 1.

我想首先，儘管第三季度美國的覆蓋率為 22%，但這並沒有完全轉化為淨收入。那麼你能否提供更多關於為什麼會這樣的顏色？是否因為可能需要額外的談判，國家層面的處方集訪問可能不會立即轉化為付款人的某些下游客戶的付費 Rx？我認為這可能是一個因素，這將有助於我們更好地了解如何考慮截至 10 月 1 日的 45% 覆蓋率。

And then second, with respect to ex U.S. sales prospects, I'm not sure if you provided this yet, but could you talk about how we should think about sales to Mitsubishi in the fourth quarter sequentially and how we should think about ex U.S. rollout plans in the context of the risk of demand outstripping manufacturing capacity?

其次，關於前美國的銷售前景，我不確定你是否提供了這個，但你能否談談我們應該如何考慮第四季度對三菱的銷售以及我們應該如何考慮前美國的推出在需求超過製造能力的風險背景下計劃？

And one other, just a quick one, just to tie to the first question about the U.S. sales. There was a comment about 40% of the sales being from stocking, but it wasn't clear if that was a U.S. comment. So if you could just clarify that when you address the first question.

還有一個，只是一個快速的，只是為了與關於美國銷售的第一個問題聯繫起來。有評論說 40% 的銷售額來自庫存，但不清楚這是否是美國的評論。因此，如果您在解決第一個問題時可以澄清這一點。

Thanks, Dave, for the question. So for the first one, we'll go to Mike to discuss a bit about coverage. And I think maybe what you're getting at is around the co-pay card. And then for the second one, we'll go to Ilya to talk about OUS sales prospects and dynamics and timing. So Mike?

謝謝，戴夫，這個問題。因此，對於第一個問題，我們將與 Mike 討論一些有關報導的問題。我想也許你得到的是圍繞共同支付卡。然後對於第二個，我們將去 Ilya 討論 OUS 的銷售前景、動態和時機。所以邁克？

Okay. Thanks, David, for the question. Yes, the percent that was coming from channel was in a U.S. figure. On the -- when you look at our data and you look at percent covered scripts that were paid versus paid through the savings card, that rate in -- since launch has closely matched our access rates. So I would say that's the best indicator for kind of the percent that are paid versus going through the bridging program.

好的。謝謝，大衛，這個問題。是的，來自渠道的百分比是美國的數字。在 - 當您查看我們的數據並查看通過儲蓄卡支付的覆蓋腳本與通過儲蓄卡支付的百分比時，該比率 - 自發布以來與我們的訪問率非常匹配。所以我會說這是支付百分比與通過過渡計劃的最佳指標。

Thanks, Mike. Ilya, on OUS?

謝謝，邁克。伊利亞，在 OUS 上？

Yes. Maybe first on Mitsubishi Tanabe and the dynamics of the upfront payment. Basically, the economics are the upfront payment and the future economics would be when we actually start commercializing and selling Mounjaro in the Japan market. So that is a onetime upfront payment. And so that's how I would look at the economics for the future.

是的。也許首先是三菱田邊和預付款的動態。基本上，經濟學是預付款，未來的經濟學將是我們真正開始在日本市場商業化和銷售 Mounjaro。所以這是一次性的預付款。這就是我對未來經濟學的看法。

In terms of overall commercialization of Mounjaro outside of the U.S., I think one of the aspects that's important for us to determine is ensuring that whenever we enter a market, that we can ensure that we can appropriately supply Mounjaro to type 2 patients in any given market.

就 Mounjaro 在美國以外的整體商業化而言，我認為我們要確定的重要方面之一是確保每當我們進入市場時，我們可以確保我們能夠在任何特定情況下為 2 型患者提供適當的 Mounjaro市場。

And we will evaluate that as well as build up our access. As you may know, for most markets outside the U.S., it takes time, and there's typically a lag between approval and also gaining access to patients for reimbursement. And so we don't anticipate that being a significant delay in the full commercialization of Mounjaro outside the U.S., but of course, we will look and monitor and ensure that we have adequate supply when we enter a market.

我們將對其進行評估並建立我們的訪問權限。您可能知道，對於美國以外的大多數市場，這需要時間，而且通常在批准和獲得患者報銷之間存在滯後。因此，我們預計 Mounjaro 在美國以外的全面商業化不會出現重大延遲，但當然，我們會關注並監控並確保我們在進入市場時有足夠的供應。

The next question is from Louise Chen from Cantor.

下一個問題來自 Cantor 的 Louise Chen。

So first question I had for you is how you see the market for all GLP-1s and injectables playing out over time. And then the second question I had for you is, do you think a positive outcome in Novo SELECT study will be enough to convince payers of the opportunity here? Or do you think they'll have to look for a broader study like your SURMOUNT-MMO? And I don't know if you said this before or not, but will you have an interim look in your SURMOUNT-MMO data?

所以我問你的第一個問題是你如何看待所有 GLP-1 和注射劑的市場隨著時間的推移而發展。然後我問你的第二個問題是，你認為 Novo SELECT 研究的積極結果是否足以讓付款人相信這裡的機會？還是您認為他們必須像您的 SURMOUNT-MMO 那樣尋找更廣泛的研究？而且我不知道您之前是否說過，但是您會臨時查看一下您的 SURMOUNT-MMO 數據嗎？

Thanks, Louise. Mike, I'll let you kind of handle both. First one is around what we see for the market for oral GLPs and then around prospects for positive SELECT study.

謝謝，路易絲。邁克，我會讓你處理這兩個問題。第一個是關於我們對口服 GLP 市場的看法，然後是關於積極 SELECT 研究的前景。

Okay. On the oral GLP market, I mean, in our market research, consumers are very interested in oral products, both in type 2 diabetes and obesity. And so the prospects of an oral anti-obesity product is very attractive. So we're very encouraged by that opportunity and are excited by our NPA program.

好的。關於口服 GLP 市場，我的意思是，在我們的市場研究中，消費者對口服產品非常感興趣，包括 2 型糖尿病和肥胖症。因此，口服抗肥胖產品的前景非常誘人。因此，我們對這個機會感到非常鼓舞，並對我們的 NPA 計劃感到興奮。

As it comes to the positive CV study, if Novo is able to get that with semaglutide, to me, it's more of an opportunity to show the benefits of the products in the class. I think any additional benefits that are represented by whether it be our trials or Novo trials are going to help the class and help more payers and more health care professionals take action on the product.

就積極的 CV 研究而言，如果 Novo 能夠通過 semaglutide 獲得這一點，對我來說，這更像是一個在課堂上展示產品益處的機會。我認為無論是我們的試驗還是 Novo 試驗所代表的任何額外好處都將有助於班級，幫助更多的付款人和更多的醫療保健專業人員對產品採取行動。

And so I think their trial will provide good information and good data for health care professionals and payers. And while our trial is a little bit different and, we think, is a little bit broader in nature, we think that will also expand it.

所以我認為他們的試驗將為醫療保健專業人員和付款人提供良好的信息和良好的數據。雖然我們的試驗有點不同，而且我們認為在性質上更廣泛，但我們認為這也會擴大它。

So to me, it's not comparing our study, the SURMOUNT-MMO study versus SELECT. It's more new information is going to be good for the class, good for health care professionals. We really should be treating obesity a lot more proactive than what we do today, and I think those trials will show the need for that.

所以對我來說，這不是比較我們的研究，SURMOUNT-MMO 研究與 SELECT。更多的新信息將對課堂有益，對醫療保健專業人員有益。我們真的應該比我們今天更積極地治療肥胖症，我認為這些試驗將表明需要這樣做。

Maybe if I could jump on this one because I'm speaking to a lot of analysts, there's a desire to anchor on one event that will then trigger broad commercial access for obesity or not. And I don't really think we think it's going to play out that way, that already, there are commercial payers who reimburse medicines for chronic weight management and obesity. It's a small number. We think as the data accumulates over the course of the balance of the decade that, that will become the norm just like we expect in hypertensives to be paid for.

也許如果我能跳上這個，因為我正在與很多分析師交談，那麼我希望錨定一個事件，然後引發肥胖症的廣泛商業准入。而且我真的不認為我們認為它會那樣發展，因為已經有商業支付者為慢性體重管理和肥胖症報銷藥物。這是一個很小的數字。我們認為，隨著數據在這十年的平衡過程中積累，這將成為常態，就像我們期望的高血壓患者一樣。

Of course, the big action might relate to TROA and the government coverage in the U.S. or similar efforts ex U.S. And those will be more binary. But I wouldn't encourage investors to think about this sort of waiting for one definitive data set, but rather a more accumulating effect over time where commercial access will slowly open up over the next many years due to both Lilly's efforts and others' efforts to prove the health benefits of chronic weight management.

當然，重大行動可能與 TROA 和美國政府的報導或美國以外的類似努力有關，而且這些將更加二元化。但我不會鼓勵投資者考慮這種等待一個明確的數據集，而是隨著時間的推移產生更多的累積效應，由於禮來的努力和其他人的努力，商業准入將在未來幾年慢慢開放證明長期體重管理的健康益處。

The next question is from Andrew Baum from Citi.

下一個問題來自花旗的 Andrew Baum。

A couple of questions, please. First, on remternetug, on the time lines on clinic trials, potentially this drug could be launched as early as '25 under accelerated approval, 1 year or so post the introduction of Roche's subcutaneous. Do you expect the evolving Abeta data to result in removing of the existing NCD in order to allow it to compete effectively? That's the first question. Obviously, at that point, you will only have the Abeta lowering data, but it will be subcutaneous potentially.

有幾個問題，請。首先，在 remternetug 上，在臨床試驗的時間表上，這種藥物可能最早在 25 年加速批准下推出，大約在羅氏皮下推出後 1 年左右。您是否期望不斷發展的 Abeta 數據能夠消除現有的 NCD 以使其有效競爭？這是第一個問題。顯然，到那時，您將只有 Abeta 降低數據，但它可能是皮下的。

And then second question, just going back to your oral GLP-1 agents, you're about to unblind both diabetes and obesity Phase II trials. Could you talk to how you look at the commercial potential for this market? It strikes me that the DPP-4 market is worth about $13 billion, and that's on top of whatever Rybelsus is doing. So once you solve or if you managed to solve the drug interaction, is there no possibility that this could be a very major contributor to your revenue growth independent to Mounjaro going forward?

然後第二個問題，回到您的口服 GLP-1 藥物，您即將揭開糖尿病和肥胖症 II 期試驗的盲區。您能否談談您如何看待這個市場的商業潛力？令我震驚的是，DPP-4 市場價值約 130 億美元，而這在 Rybelsus 所做的一切之上。因此，一旦您解決了或如果您設法解決了藥物相互作用，這是否不可能成為您未來獨立於 Mounjaro 的收入增長的主要貢獻者？

Thanks, Andrew, for the question. So for the first one on remternetug and the time lines, I'll maybe hand to Anne to chime in as well as the NCD removal dynamics. And then for the second one on the commercial potential for oral GLPs, we'll go back to Mike.

謝謝，安德魯，這個問題。因此，對於 remternetug 和時間線的第一個問題，我可能會交給 Anne 來插話，以及 NCD 移除動態。然後關於口服 GLP 的商業潛力的第二個問題，我們將回到 Mike。

Thanks so much for the question on remternetug. Obviously, we're excited that we've initiated the Phase III program. And as you noted, we've started the first study, which is to assess amyloid lowering. We have a broader Phase III program that we're initiating as well, looking at the clinical endpoints as we've done for donanemab, but we're excited about what we're seeing so far with remternetug, which is next generation.

非常感謝關於 remternetug 的問題。顯然，我們很高興我們已經啟動了第三階段計劃。正如你所指出的，我們已經開始了第一項研究，即評估澱粉樣蛋白的降低。我們還有一個更廣泛的 III 期計劃，我們也在啟動該計劃，研究我們對 donanemab 所做的臨床終點，但我們對迄今為止看到的下一代 remternetug 感到興奮。

And so you're going to see us continue to invest in the AD platform going forward based on donanemab's compelling data and then what we're seeing early with remternetug. And as you said, it offers the convenience of an additional dosing form that we think will offer a lot of convenience to patients.

因此，您將看到我們基於 donanemab 令人信服的數據以及我們早期看到的 remternetug 繼續投資於 AD 平台。正如您所說，它提供了一種額外劑量形式的便利，我們認為這將為患者提供很多便利。

On your question around the NCD, obviously, we hope now that CMS -- we now have the Phase II data from donanemab, which clearly showed clinical benefit as well as clearance of plaque. Now we have the lecanemab data, a large Phase III study also showing clinical benefit. Certainly, it's our position that this is time for CMS to reconsider this decision. So certainly, we would hope that this is resolved before remternetug reads out.

關於你關於 NCD 的問題，顯然，我們現在希望 CMS——我們現在有來自 donanemab 的 II 期數據，它清楚地顯示了臨床益處以及斑塊的清除。現在我們有了 lecanemab 數據，一項大型 III 期研究也顯示出臨床益處。當然，我們的立場是，現在是 CMS 重新考慮這一決定的時候了。所以當然，我們希望在 remternetug 讀出之前解決這個問題。

Obviously, the time line though, is not clear. So what you'll see us do, I'm sure Eisai is doing the same, is as soon as we have that Phase III data requesting reconsideration and moving forward. With the evidence that's demonstrated today, we cannot see a reason that CMS will continue to prevent Alzheimer's patients from getting these medicines.

顯然，時間線雖然不清楚。所以你會看到我們做的，我相信衛材也在做同樣的事情，一旦我們有第三階段的數據要求重新考慮並繼續前進。根據今天所展示的證據，我們看不出 CMS 將繼續阻止阿爾茨海默病患者獲得這些藥物的原因。

And as we've stated in the past, we believe CD really is very restrictive method to provide to the patients who have this disease and also leads to disparity we've seen in care for Alzheimer's disease. So certainly, I hope that this will be resolved by the time we have remternetug available to patients.

正如我們過去所說，我們認為 CD 確實是一種非常嚴格的方法來提供給患有這種疾病的患者，並且也導致我們在治療阿爾茨海默病方面看到的差異。因此，當然，我希望在我們為患者提供 remternetug 時，這將得到解決。

Thanks, Anne. Mike, anything to add in terms of the oral GLP commercial opportunity?

謝謝，安妮。邁克，關於口服 GLP 商業機會，有什麼要補充的嗎？

Andrew, I think you're thinking about it correctly. When Rybelsus launched, we expected it to grow the class, not impact the injectable market, and that's exactly what happened. It was more additive to the class.

安德魯，我認為你的想法是正確的。當 Rybelsus 推出時，我們預計它會擴大類別，而不是影響注射劑市場，而這正是發生的事情。它對課堂更具附加性。

And then as Mounjaro was launched, we only see 1% of Mounjaro's demand coming from Rybelsus or oral GLP. So I think you're right. I think it is additive versus attractive, and we're very pleased with the opportunity.

然後隨著 Mounjaro 的推出，我們只看到 Mounjaro 的 1% 的需求來自 Rybelsus 或口服 GLP。所以我認為你是對的。我認為它是附加的而不是有吸引力的，我們對這個機會感到非常高興。

I think in the oral market, what's going to be key is Rybelsus has some interactions with water and food, which have some dosing limitations, which can impact the efficacy of the product if it's not followed closely, as well as there's a gap between the efficacy of oral Rybelsus and injectables. So I think as you get alternatives in place that doesn't have that food and water interaction as the efficacy of the orals increase, you'll see the market potential even being higher, and that's exactly what we plan to deliver, hopefully, with NPA.

我認為在口服市場中，關鍵是 Rybelsus 與水和食物有一些相互作用，這有一些劑量限制，如果不密切關注，可能會影響產品的功效，以及兩者之間存在差距口服 Rybelsus 和注射劑的功效。因此，我認為，隨著口服藥物功效的提高，當您獲得不存在食物和水相互作用的替代品時，您會看到市場潛力甚至更高，而這正是我們計劃提供的，希望通過新苯丙胺。

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

下一個問題來自 BMO Capital Markets 的 Evan Seigerman。

One on Mounjaro. It seems like it's a Mounjaro call. I'm looking at the outcome trial. Can you comment on kind of the relative risk reduction you'd like to see in the primary endpoint? If you can't comment on any of the (inaudible) plan, talk more about the need for outcomes to gain payer access over time.

一個在蒙扎羅。好像是蒙扎羅的電話。我在看結果審判。您能否評論一下您希望在主要終點中看到的相對風險降低類型？如果您無法對任何（聽不清）計劃發表評論，請更多地談論隨著時間的推移獲得付款人訪問權限的結果的需要。

And my second question is on CLARITY AD, and I appreciate your positive comments around the trial. But do you believe the bar for efficacy has been raised with these data? And can you just remind us why you believe that your endpoint iADRS will be sufficient for full FDA approval and any potential coverage by CMS and other payers?

我的第二個問題是關於 CLARITY AD 的，感謝您對試驗的積極評價。但是你認為這些數據提高了療效標準嗎？您能否提醒我們為什麼您認為您的端點 iADRS 足以獲得 FDA 的全面批准以及 CMS 和其他付款人的任何潛在覆蓋？

Thanks, Evan. So for the first question on Mounjaro, the kind of outcomes trial and what we'd need for payer access, I'll hand that over to Mike. And then for the CLARITY AD, I'll hand over to Anne.

謝謝，埃文。因此，對於關於 Mounjaro 的第一個問題，結果試驗的類型以及我們需要哪些付款人訪問權限，我將把它交給邁克。然後對於 CLARITY AD，我將交給 Anne。

Okay. Maybe I'll take another shot at obesity access and how we see it develop over time. I think Dave talked about back -- if it's going to take a steady drumbeat of evidence and every payer, every employer will make the decision independently and that will grow over time.

好的。也許我會再試一次關於肥胖的訪問以及我們如何看待它隨著時間的推移而發展。我認為戴夫回過頭來說——如果需要穩定的證據和每個付款人，每個雇主都會獨立做出決定，並且會隨著時間的推移而增長。

The other approach that we're taking is we're studying tirzepatide for other indications for people who live with obesity like heart failure and sleep apnea. These are indications that are already supported by commercial and Medicare Part D.

我們正在採取的另一種方法是，我們正在研究替西帕肽的其他適應症，用於患有肥胖症的人，如心力衰竭和睡眠呼吸暫停。這些適應症已經得到商業和醫療保險 D 部分的支持。

And so we believe that as we get access and demonstrate efficacy there and get indications that, that in itself will unlock subsets of payer access for people who live with obesity who have sleep apnea or have heart failure as we continue to build toward our -- the results of the MMO study. So I think it will grow over time, but I think those 2 events are important events in the life cycle of tirzepatide.

因此，我們相信，當我們獲得訪問權限並在那裡展示療效並獲得跡象表明，這本身將為患有睡眠呼吸暫停或心力衰竭的肥胖患者解鎖付款人訪問的子集，因為我們將繼續朝著我們的方向發展—— MMO研究的結果。所以我認為它會隨著時間的推移而增長，但我認為這兩個事件是 tirzepatide 生命週期中的重要事件。

Thanks, Mike. Anne?

謝謝，邁克。安妮？

Well, thanks for the question on the CLARITY AD. And maybe getting to your question, we absolutely see the data that we saw there as clinically meaningful. And clearly, patients, families, care partners highly value a delay in loss of independence and abilities. And so a 20% to 30% slowing of the disease initiated in the earliest stage of the disease should mean additional time in the more functional, less impaired stages. So we're excited about those results, and we do think that they're clinically meaningful in this space.

好吧，感謝關於 CLARITY AD 的問題。也許談到你的問題，我們絕對認為我們在那裡看到的數據具有臨床意義。顯然，患者、家人、護理夥伴高度重視延遲喪失獨立性和能力。因此，在疾病的最早階段開始的疾病減緩 20% 到 30% 應該意味著在功能更強大、受損程度更小的階段有更多的時間。所以我們對這些結果感到興奮，我們確實認為它們在這個領域具有臨床意義。

And so we look forward, as we've said, to what we'll see with donanemab. There are many reasons that we're extremely confident about donanemab, and those haven't changed. So obviously, it's a positive Phase II study that we were able to produce the choice of the endpoint that we have in our study, as you commented, patient selection strategy and then importantly, the speed and the depth of plaque clearance. So we remain very confident in what we'll see out of our upcoming readout on TB2.

因此，正如我們所說，我們期待著我們將在 donanemab 上看到的東西。有很多原因讓我們對 donanemab 非常有信心，而且這些都沒有改變。很明顯，這是一項積極的 II 期研究，我們能夠選擇我們在研究中擁有的終點，正如您所評論的那樣，患者選擇策略，然後重要的是，斑塊清除的速度和深度。因此，我們對即將發布的關於 TB2 的讀數非常有信心。

And then your question on iADRS, I think that just as we've said in the past, we believe that iADRS is the most robust endpoint in this space. And we've always believed that CDR Sum of Boxes can be a bit of a noisy endpoint, and so indexing on exact numbers is probably not the best move there.

然後你關於 iADRS 的問題，我認為正如我們過去所說，我們相信 iADRS 是這個領域最強大的端點。而且我們一直認為 CDR Sum of Boxes 可能是一個嘈雜的端點，因此對精確數字進行索引可能不是最好的做法。

But on TRAILBLAZER-ALZ, we powered it for iADRS. We showed a 32% slowing, which we definitely see as clinically meaningful. And we believe that iADRS will always perform closest to the truth. But in a large enough study, we expect all the endpoints will move similarly. So we continue to be confident about the choice of the iADRS. We continue to be confident about the TB2 readout that we'll see in mid-2023.

但是在 TRAILBLAZER-ALZ 上，我們為 iADRS 提供了動力。我們顯示了 32% 的放緩，我們絕對認為這具有臨床意義。我們相信 iADRS 的表現總是最接近真相。但在一項足夠大的研究中，我們預計所有端點都會以類似方式移動。因此，我們繼續對 iADRS 的選擇充滿信心。我們繼續對我們將在 2023 年年中看到的 TB2 讀數充滿信心。

The next question is from Tim Anderson from Wolfe Research.

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

If I could just stay on Alzheimer's for a minute. Just your latest views on the next big readout here coming up, which is the Roche data. To put it bluntly, do you expect that this readout is going to fail even downstream of lecanemab? It seems to me like you guys are still cautious on that data. What's your latest thinking?

如果我能在阿爾茨海默病上呆一分鐘就好了。只是你對即將到來的下一個大讀數的最新看法，即羅氏數據。坦率地說，您是否認為該讀數即使在 lecanemab 的下游也會失敗？在我看來，你們對這些數據仍然持謹慎態度。你最近的想法是什麼？

Second question, Anat mentioned pushes and pulls in 2023 and something about donanemab. My question is, are you expecting donanemab approval in 2023?

第二個問題，Anat 提到了 2023 年的推拉和有關 donanemab 的一些事情。我的問題是，您是否期望在 2023 年獲得 donanemab 批准？

And then third question, just your views of the ARIA-E data by lecanemab and whether you think that's important and clinically differentiating. Because that does seem to be a real issue that KOLs talk about a lot, and they have the best data so far.

然後是第三個問題，只是您對 lecanemab 的 ARIA-E 數據的看法，以及您認為這是否重要和臨床區分。因為這似乎確實是 KOL 經常談論的一個真實問題，而且他們擁有迄今為止最好的數據。

Thanks, Tim. And you got an extra question in there out of the 2. But we'll go to Anne maybe to comment high level on Roche and then also on the pushes/pulls for donanemab expectations for timing and then finally, lecanemab differentiation maybe on the Roche. Maybe Dan, give your thoughts first.

謝謝，蒂姆。你在 2 中還有一個額外的問題。但是我們可能會去 Anne 對羅氏發表高水平的評論，然後也會對多納尼瑪對時機的期望的推動/拉動，最後，lecanemab 的差異化可能在羅氏.也許丹，先說出你的想法。

Okay. Yes. And then I'll -- I think your last question there, Tim, was on ARIA-E rates, which I'll maybe take as well. So again, donanemab, I think I've said before, there's a number of factors here that can help us in predicting results of amyloid-lowering drugs. Probably the most important one in our view is the degree of amyloid lowering and there, we're really pleased with what we've seen with donanemab. But lecanemab is probably also a pretty powerful amyloid-lowering drug.

好的。是的。然後我會 - 我想你的最後一個問題，蒂姆，是關於 ARIA-E 費率的，我可能也會接受。再說一次，多那奈馬，我想我之前說過，這裡有許多因素可以幫助我們預測降低澱粉樣蛋白的藥物的結果。在我們看來，最重要的可能是澱粉樣蛋白降低的程度，在那裡，我們對我們所看到的 donanemab 感到非常滿意。但 lecanemab 可能也是一種非常強大的降低澱粉樣蛋白的藥物。

Certainly a positive readout from a Phase III of one of these 3 drugs is going to increase your odds of success of one of -- or both of the other 2. But I'd just sort of remind us all that Alzheimer's has been a risky area with studies that are sometimes hard to predict. So we take some caution. Of course, we'd love to see more positive studies and more news for patients -- good news for patients.

當然，從這 3 種藥物中的一種進行 III 期臨床試驗的陽性結果會增加您在另一種藥物中的一種或兩種藥物中成功的機率。但我只是想提醒我們所有人，阿爾茨海默氏症是一種危險的疾病研究有時難以預測的領域。所以我們要謹慎一些。當然，我們希望看到更多積極的研究和更多的患者消息——對患者來說是個好消息。

I think before I turn it over to Anne for the other question, I'd just sort of take ARIA-E and lecanemab data. I think it's a little bit hard to do cross-trial comparisons of ARIA rates for a couple of reasons that I think are important, maybe we can talk more about at our scientific presentation at CTAD. Just sort of noting that TRAILBLAZER-4 is probably the first time anyone's ever done within trial comparison of 2 different drugs to be able to compare ARIA.

我想在我把它交給 Anne 來回答另一個問題之前，我只需要獲取 ARIA-E 和 lecanemab 的數據。我認為對 ARIA 比率進行交叉試驗比較有點困難，原因有幾個我認為很重要，也許我們可以在 CTAD 的科學演講中討論更多。只是注意到 TRAILBLAZER-4 可能是第一次有人在試驗中比較兩種不同的藥物以比較 ARIA。

Why is that important? When you're looking at 2 different trials, first of all, you have different patient populations. I think we'll probably learn over time that ARIA rates depend on the stage of disease and are more common in patients with more severe brain pathology. I think that's likely to be true.

為什麼這很重要？當您查看 2 個不同的試驗時，首先，您有不同的患者群體。我想隨著時間的推移，我們可能會了解到 ARIA 率取決於疾病的階段，並且在腦部病變更嚴重的患者中更常見。我認為這很可能是真的。

Second, even in the same population, how you measure ARIA can be very different in different trials, for example. Lecanemab has different timings of MRI than donanemab has used. If you have more MRIs or earlier MRIs as we do, I think, you're more likely to pick up more radiographic ARIA. So that's another caution on cross-trial comparisons.

其次，即使在相同的人群中，例如，在不同的試驗中，您測量 ARIA 的方式也可能會大不相同。 Lecanemab 的 MRI 時間與 donanemab 使用的時間不同。如果您像我們一樣有更多的 MRI 或更早的 MRI，我認為，您更有可能獲得更多的放射學 ARIA。所以這是對交叉試驗比較的另一個警告。

However, I do see ARIA rates as important, particularly the symptomatic ARIA that results in serious consequences in some patients. And that's probably what we need to focus on, is the serious events rather than radiographic ARIA. Anne?

然而，我確實認為 ARIA 發生率很重要，尤其是對某些患者造成嚴重後果的症狀性 ARIA。這可能是我們需要關注的，是嚴重的事件而不是放射學 ARIA。安妮？

Yes. And then the timing, so as I think Dan mentioned during his words that we expect the data readout for TRAILBLAZER-ALZ 2 in mid-'23. So our intention is to submit the data rapidly, and we expect a timely review from the FDA for a supplemental submission. So that could lead to a traditional approval in the first half of 2024.

是的。然後是時機，正如我認為丹在講話中提到的那樣，我們預計 TRAILBLAZER-ALZ 2 的數據讀數會在 23 年中期公佈。因此，我們的目的是快速提交數據，我們希望 FDA 及時審查補充提交。因此，這可能會導致 2024 年上半年獲得傳統批准。

And we certainly -- as I mentioned, we expect that we would drive for reconsideration. We certainly hope that CMS would take that Phase III data and not wait for the traditional approval to assess the situation. But then maybe also to your comment, we expect really limited uptake in the time of accelerated approval, which as we said, is in early '23 based on how the CED is currently written. So that's the time line that we're on.

我們當然 - 正如我所提到的，我們希望我們會推動重新考慮。我們當然希望 CMS 能夠獲取 III 期數據，而不是等待傳統的批准來評估情況。但是，也許您的評論也是如此，我們預計在加速批准期間的吸收確實有限，正如我們所說，根據 CED 目前的編寫方式，這是在 23 年初。這就是我們所處的時間線。

The next question is from Kerry Holford from Berenberg.

下一個問題來自貝倫貝格的 Kerry Holford。

[You got 2 from me.] Just for SURMOUNT-MMO, following up on that, just keen to understand why you're [veering] away to a more traditional 3-point base that's been used in diabetes under the SELECT study. What evidence do you have adding those 2 additional endpoints? And also, why are you exploring all-cause mortality rather than CV death? Do you think inclusion of those endpoints and your broader eligibility criteria will expedite events?

[你從我這裡得到了 2 分。] 只是為了 SURMOUNT-MMO，跟進這件事，只是想了解為什麼你 [轉向] 轉向在 SELECT 研究下用於糖尿病的更傳統的 3 點基礎。你有什麼證據添加這兩個額外的端點？而且，你為什麼要探索全因死亡率而不是心血管死亡？您是否認為包含這些端點和您更廣泛的資格標準會加快事件的發生？

And then secondly, a question on therapeutic focus. You've taken the decision to move your ANGPTL3 into Phase II in cardiovascular disease. CV can be, I guess, an expensive, risky therapeutic category to participate in. So assuming Phase II is positive, do you anticipate taking these pipelines, the assets all the way through to market alone? Or might you need to consider partnership? Just your thought processes around this development decision would be [appreciated.]

其次，關於治療重點的問題。您已決定將您的 ANGPTL3 轉移到心血管疾病的 II 期。我想，CV 可能是一個昂貴且有風險的治療類別。因此，假設第二階段是積極的，您是否預計將這些管道、資產一直單獨推向市場？或者您可能需要考慮合作夥伴關係？只是您圍繞此開發決策的思考過程將[讚賞。]

Thanks, Kerry. Okay. So first question on SURMOUNT-MMO design and second one on ANGPTL3 and ASCVD maybe more in general, Dan?

謝謝，克里。好的。所以關於 SURMOUNT-MMO 設計的第一個問題和關於 ANGPTL3 和 ASCVD 的第二個問題可能更籠統，丹？

Yes. Thanks. Two thoughtful questions there, Kerry. So starting with the SURMOUNT-MMO, you sort of asked why did we -- why are we doing more typical CV outcome studies in -- of course, you'll know that for drugs in diabetes, there was sort of an FDA requirement around this in the past that sort of focus people's attention on discharging risk. And then ultimately, we discovered that certain classes of drugs can actually provide a benefit.

是的。謝謝。有兩個深思熟慮的問題，克里。所以從 SURMOUNT-MMO 開始，你有點問我們為什麼——為什麼我們要做更典型的 CV 結果研究——當然，你會知道對於糖尿病藥物，有一種 FDA 的要求這在過去那種將人們的注意力集中在釋放風險上。然後最終，我們發現某些類別的藥物實際上可以提供益處。

Here, we're trying to go even beyond that observation and demonstrate what we believe to be true, which is that correcting obesity and correcting metabolism in these patients can have a wide range of benefits. And so that's why we've done 2 things there. We've gone beyond the traditional cardiovascular endpoints. This is primarily a cardiovascular drug. It's a drug that corrects metabolism. And we think that will have broader benefits, including, hopefully, and importantly, all-cause mortality. And then second, we've got to a broader population so that we can show the benefit in that group. So that's our thinking here. And I think it's a natural evolution of this class of drugs as we go forward.

在這裡，我們試圖超越這一觀察並證明我們認為是真實的，即糾正這些患者的肥胖和新陳代謝可以帶來廣泛的好處。這就是為什麼我們在那裡做了兩件事。我們已經超越了傳統的心血管終點。這主要是一種心血管藥物。這是一種糾正新陳代謝的藥物。我們認為這將帶來更廣泛的好處，包括，希望且重要的是，全因死亡率。其次，我們必須覆蓋更廣泛的人群，以便我們可以展示該群體的好處。這就是我們的想法。我認為隨著我們的發展，這是這類藥物的自然演變。

With respect to ANGPTL3, you asked about our Phase II and what do we do if we get a positive result. Of course, the reason we do these Phase II trials is to look for promising drugs for patients. I think in cardiovascular, you rightly point out that it's a high-risk area with big Phase III studies that sometimes carry risk into them. In this case, there's a reasonable understanding of this mechanism and how to translate from 2 to 3 -- Phase II to Phase III.

關於 ANGPTL3，您詢問了我們的第二階段以及如果我們得到積極的結果我們該怎麼辦。當然，我們進行這些 II 期試驗的原因是為患者尋找有前景的藥物。我認為在心血管領域，您正確地指出這是一個高風險領域，有大型 III 期研究，有時會帶來風險。在這種情況下，對這種機制以及如何從 2 轉換為 3 —— Phase II 到 Phase III 有一個合理的理解。

But still, what we're focused on is finding a large effect size drug here. And if we can see a big effect in Phase II that would predict a positive strong signal in a Phase III cardiovascular outcome study, then that's exactly what we'll do. In terms of whether that's something Lilly does alone or partners, it's probably premature to talk about anything like that.

但是，我們仍然關注的是在這裡找到一種大效應量的藥物。如果我們能在 II 期看到一個巨大的影響，在 III 期心血管結果研究中預測一個積極的強信號，那麼這正是我們要做的。至於這是禮來公司單獨做的事情還是合作夥伴做的事情，現在談論這樣的事情可能還為時過早。

Thanks, Kerry. Lois, you want to take us to the last question?

謝謝，克里。 Lois，你想帶我們回答最後一個問題嗎？

And that's from Robyn Karnauskas from Truist Securities.

這是來自 Truist Securities 的 Robyn Karnauskas。

I guess my first question is on Mounjaro. So we talked -- you talked the whole call, I think, about supply and trends. But can you talk a little bit about the individual dosing? Like what doses are being used the most? And if you do incur like higher than what you predict demand, what dosage levels might be greatest impacted? I think you had 30% switching and 70% new. So it's the low doses that would go first or the mid-doses?

我想我的第一個問題是關於 Mounjaro 的。所以我們談了 - 我認為你談到了供應和趨勢的整個電話。但是你能談談個人劑量嗎？比如使用最多的劑量是多少？如果您的需求量確實高於您預測的需求量，那麼哪些劑量水平可能受到的影響最大？我認為你有 30% 的轉換和 70% 的新。那麼首先是低劑量還是中劑量？

And second, on Alzheimer's, we're hearing a lot of doctors say that you have the mindshare of the [voice] for Abeta class drugs. Can you talk a little bit about what you think is the most important thing that resonates with doctors? Is it subcu? Is it infrequent dosing? Is it the magnitude of benefit as we think about the speed of uptake once full drug is reimbursed?

其次，關於阿爾茨海默氏症，我們聽到很多醫生說你對 Abeta 類藥物的[聲音] 有心聲。你能談談你認為最能引起醫生共鳴的事情嗎？是亞庫嗎？是不是經常用藥？當我們考慮到全部藥物報銷後的吸收速度時，它是不是收益的幅度？

Thanks, Robyn. So Mike, do you want to handle the question on the dosing dynamics? And then with regard to AD and that mindshare question, Anne will fill that. Mike?

謝謝，羅賓。那麼邁克，你想處理劑量動力學的問題嗎？然後關於 AD 和那個思想共享問題，Anne 會回答這個問題。麥克風？

Yes, I'm happy to answer that question. I think dosing titration in the real world is different than our clinical studies. In the clinical studies, we needed to test what the dose response was going to be at 5, 10 and 15. So in our clinical studies, we titrated every 4 weeks up to additional doses in order to be able to have expedited trials and show the benefit.

是的，我很高興回答這個問題。我認為現實世界中的劑量滴定與我們的臨床研究不同。在臨床研究中，我們需要測試在 5、10 和 15 時的劑量反應。因此在我們的臨床研究中，我們每 4 週滴定一次，直至增加劑量，以便能夠加快試驗並顯示的好處。

In real world, what you see is that people will start on a dose. They start at 2.5. They'll go to 5. And then what we're seeing is that physicians will hold there and see how they'll respond in 5 milligrams, provides really good efficacy for people living with type 2 diabetes. If they need more, then they'll escalate the dose. It may not be at the 4-week mark, it maybe at a 3-month mark. So those trends are still established in the marketplace, but the vast majority of our volume is in the 2.5 and 5 milligrams.

在現實世界中，你看到的是人們會開始服用劑量。它們從 2.5 開始。他們會去 5。然後我們看到的是，醫生會堅持在那裡，看看他們在 5 毫克內會有什麼反應，這為 2 型糖尿病患者提供了非常好的療效。如果他們需要更多，那麼他們會增加劑量。它可能不在 4 周大關，它可能在 3 個月大關。因此，這些趨勢仍然在市場上確立，但我們的絕大多數銷量是 2.5 和 5 毫克。

I want to make sure you're not reading too much into my earlier comments around shortages at any particular dose. My comments earlier were just saying, hey, there's a lot of factors that's going on. There's a lot of dynamics. You've got to plan your manufacturing down at the SKU dosing levels a month or 2 ahead of actually when it's produced.

我想確保你不會過多地閱讀我之前關於任何特定劑量短缺的評論。我之前的評論只是說，嘿，有很多因素正在發生。有很多動態。您必須在實際生產前一個月或 2 個月按 SKU 劑量水平計劃您的生產。

And so will every dose line up perfectly with what the demand is needed for that week in the marketplace? It may not. And if it does, then a dose or 2 may not be able to get the order that week, and then we'll adjust quickly. And our team work very closely and very hard to make sure it doesn't impact patients.

那麼每個劑量是否會完全符合該週市場所需的需求？它可能不會。如果是這樣，那麼一兩劑可能無法獲得那週的訂單，然後我們會迅速調整。我們的團隊密切合作，非常努力地確保它不會影響患者。

Great. And then thanks for the comment on having the mindshare. We appreciate that. And I think -- as I reflect on that question, which is a good one, I think it's built over the decades that we've been investing in the Alzheimer's space. So we've been at this for more than 30 years, invested quite a bit of time and resources in this. And I think it led to, first of all, diagnostics being significantly evolved in this space with the launch of Amyvid and that we have Tauvid, and then we also intend to launch a P-tau blood diagnostic next year, which could really improve access and diagnosis of these patients.

偉大的。然後感謝您對擁有心靈共享的評論。我們對此表示讚賞。而且我認為 - 當我思考這個問題時，這是一個很好的問題，我認為它是在我們在阿爾茨海默氏症領域投資的幾十年中建立起來的。所以我們已經在這方面工作了 30 多年，在這方面投入了大量的時間和資源。我認為，首先，隨著 Amyvid 的推出和我們擁有 Tauvid 的推出，診斷在這個領域得到了顯著發展，然後我們還打算明年推出 P-tau 血液診斷，這可以真正改善訪問和這些患者的診斷。

And so I think it starts out there with showing our commitment to making sure that the right patients get on these therapies. And I do believe that, that was one of the pivot points for how we now have successful trials in this space by the ability to really confirm that people have this diagnosis.

因此，我認為首先要表明我們致力於確保正確的患者接受這些療法。而且我確實相信，這是我們現在如何通過真正確認人們有這種診斷的能力在這個領域進行成功試驗的關鍵點之一。

All of that learning over the years, all of the insights from the trials that we've had, some of the setbacks that we experienced led to the first positive trial that has happened in this space with the TRAILBLAZER-ALZ and showing both significant and rapid clearance of amyloid plaque, but then most importantly, to everyone showing that, that truly slows the progression of the disease.

多年來的所有學習，我們從試驗中獲得的所有見解，我們經歷的一些挫折導致了在這個領域發生的第一次積極的試驗，即 TRAILBLAZER-ALZ 並顯示出顯著和澱粉樣斑塊的快速清除，但最重要的是，向每個人表明，這確實減緩了疾病的進展。

And so it's really -- I think some of that mindshare is built on the commitment that we've shown to the space, the commitment we've had to making sure that patients truly get diagnosed in that. And that's what we're spending a lot of time in the first few months certainly of next year as we work towards access for these patients, is to make sure that we can drive early and accurate diagnosis.

所以這真的是——我認為這種思想分享是建立在我們對這個領域所展示的承諾的基礎上的，我們必須確保患者真正得到診斷的承諾。這就是我們在明年頭幾個月花費大量時間，因為我們努力為這些患者提供服務，以確保我們能夠推動早期和準確的診斷。

We're so pleased with how donanemab has continued to perform. As I said, we believe, and I think lecanemab's results reinforce what we saw in TRAILBLAZER-ALZ, is that clearance of plaque is the key to this disease. And we know that donanemab does that. We look forward to sharing the TB4 data at CTAD. I think you'll see how that reinforces what we saw in TRAILBLAZER-ALZ and then the design and what we believe will be the performance in TB2.

我們對 donanemab 的持續表現感到非常滿意。正如我所說，我們相信，而且我認為 lecanemab 的結果強化了我們在 TRAILBLAZER-ALZ 中看到的情況，即斑塊的清除是這種疾病的關鍵。我們知道 donanemab 就是這樣做的。我們期待在 CTAD 上分享 TB4 數據。我想你會看到這如何加強我們在 TRAILBLAZER-ALZ 中看到的內容，然後是設計以及我們相信 TB2 中的性能。

So I think that we deserve that mindshare, but I think it's been earned over many years of supporting and investing in this space that has led to positive trials for us and for others. So it's rewarding, I think, for many of the scientists here to see the culmination of this. So -- but again, exciting times, cusp of real meaningful movement for people with Alzheimer's disease. And we really look forward to that readout next year and our accelerated approval early next year as well. Thank you.

因此，我認為我們值得擁有這種思想分享，但我認為這是多年來對這個領域的支持和投資所獲得的，這為我們和其他人帶來了積極的考驗。因此，我認為，對於這裡的許多科學家來說，看到這一成果的高潮是值得的。所以——但又是激動人心的時刻，阿爾茨海默病患者真正有意義的運動的風口浪尖。我們真的很期待明年的讀數以及明年初我們的加速批准。謝謝你。

Thanks, Robyn, for the question. Lois, I think we're done.

謝謝羅賓的問題。露易絲，我想我們已經完成了。

And there's no further questions in queue.

隊列中沒有其他問題。

All right. Thanks, Joe, and thanks to the rest of the Lilly team. I appreciate everyone hanging with us on today's call and for your interest in our company. Please follow up with the IR team if you have any questions that we did not address. Everyone, have a great day. Thanks.

好的。謝謝，喬，也感謝禮來團隊的其他成員。感謝大家在今天的電話中與我們在一起，感謝您對我們公司的興趣。如果您有任何我們未解決的問題，請與 IR 團隊聯繫。大家，有一個美好的一天。謝謝。

Thank you. Ladies and gentlemen, this conference is available for replay beginning at 12:45 today and running through November 8 at midnight. You may access the AT&T replay system at any time by dialing (866) 207-1041 and entering the access code 3052026. International callers can dial (402) 970-0847. That does conclude our conference for today. Thank you for your participation and for using AT&T teleconference. You may now disconnect.

謝謝你。女士們先生們，本次會議可從今天 12:45 開始重播，一直持續到 11 月 8 日午夜。您可以隨時撥打 (866) 207-1041 並輸入訪問代碼 3052026 訪問 AT&T 重播系統。國際呼叫者可以撥打 (402) 970-0847。這確實結束了我們今天的會議。感謝您的參與和使用 AT&T 電話會議。您現在可以斷開連接。