禮來公司 (LLY) 2021 Q2 法說會逐字稿

Ladies and gentlemen, thank you for standing by, and welcome to Lilly's Q2 Earnings Call. (Operator Instructions) As a reminder, today's conference is being recorded. I would now like to turn the conference over to your host, Vice President of Investor Relations, Kevin Hern. Please go ahead.

女士們，先生們，感謝你們的支持，歡迎來到禮來公司的第二季度財報電話會議。 （操作員說明）提醒一下，今天的會議正在錄製中。我現在想將會議轉交給您的主持人，投資者關係副總裁 Kevin Hern。請繼續。

Good morning. Thank you for joining us for Eli Lilly and Company's Q2 2021 Earnings Call. I'm Kevin Hern, Vice President of Investor Relations. And joining me on today's call are: Dave Ricks, Lilly's Chairman and CEO; Anat Ashkenazi, Chief Financial Officer; Dr. Dan Skovronsky, Chief Scientific and Medical Officer; Anne White, President of Lilly Oncology; Ilya Yuffa, President of Lilly Biomedicines; Mike Mason, President of Lilly Diabetes; and Jake Van Naarden, CEO of Loxo Oncology at Lilly. We're also joined by Lauren Zierke, Kento Ueha and Sara Smith of the Investor Relations team.

早上好。感謝您參加禮來公司的 2021 年第二季度財報電話會議。我是投資者關係副總裁 Kevin Hern。和我一起參加今天電話會議的還有：禮來公司董事長兼首席執行官戴夫·里克斯； Anat Ashkenazi，首席財務官； Dan Skovronsky 博士，首席科學和醫學官；禮來腫瘤學總裁 Anne White； Ilya Yuffa，禮來生物醫藥總裁；禮來糖尿病總裁 Mike Mason；和禮來公司 Loxo 腫瘤學首席執行官 Jake Van Naarden。投資者關係團隊的 Lauren Zierke、Kento Ueha 和 Sara Smith 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 a number of factors, including those listed on Slide 3. Additional information concerning factors that could cause actual results to differ materially is contained in our latest Forms 10-K and subsequent Forms 10-Q and 8-K filed with the Securities and Exchange Commission. 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, a reminder that our commentary will focus on non-GAAP financial measures.

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，包括幻燈片 3 中列出的因素，我們的實際結果可能存在重大差異。有關可能導致實際結果存在重大差異的因素的其他信息包含在我們最新的表格 10-K 和後續表格 10-Q 和 8-中K 向證券交易委員會提交了申請。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，提醒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 for a summary of our second quarter results.

現在，我將把電話轉給戴夫，以獲得我們第二季度業績的摘要。

Thank you, Kevin. Q2 of last year was the peak of the pandemic's negative impact to our business. And 1 year later, I'm proud of the innovation and resilience displayed by my Lilly colleagues to deliver against our objectives in new ways while also mobilizing to develop treatments to help combat COVID-19.

謝謝你，凱文。去年第二季度是大流行對我們業務的負面影響的高峰期。一年後，我為我的禮來同事所展現的創新和韌性感到自豪，他們以新的方式實現我們的目標，同時動員起來開發治療方法來幫助對抗 COVID-19。

Looking at Q2 2021. We were encouraged by the increasing worldwide vaccination rates as well as the underlying environment in most of our major markets. COVID-19-related stocking in Q1, followed by destocking in Q2 of last year, complicates quarterly performance comparisons. Therefore, looking at revenue growth in the first half of 2021 better reflects the underlying trends in our business.

展望 2021 年第二季度。全球疫苗接種率的提高以及我們大多數主要市場的潛在環境令我們感到鼓舞。第一季度與 COVID-19 相關的庫存，隨後是去年第二季度的去庫存，使季度業績比較變得複雜。因此，著眼於 2021 年上半年的收入增長更好地反映了我們業務的基本趨勢。

On today's call, we will provide year-over-year comparisons for both Q2 and the first half of the year. In the first half of 2021, we delivered 11% growth in our core business. This excludes COVID-19 antibody revenue. This was buoyed by strong volume-driven growth across key brands and major geographies, including the U.S., Europe and China.

在今天的電話會議上，我們將提供第二季度和上半年的同比比較。 2021 年上半年，我們的核心業務實現了 11% 的增長。這不包括 COVID-19 抗體收入。這得益於主要品牌和主要地區（包括美國、歐洲和中國）的強勁銷量增長。

Turning specifically to Q2. Revenue grew 23% compared to Q2 2020 or 20% in constant currency. This performance was driven entirely by volume growth of 22 percentage points. As previously highlighted in Q2 2020, we saw a reversal of the $250 million pandemic-related product stocking, which occurred in Q1 2020. When excluding COVID-19 antibody revenue, the Q2 2020 COVID-19-related destocking and the sale of Cialis in China, our core business grew 12% for the quarter, up from 7% in Q1 on the same basis.

具體轉向第二季度。與 2020 年第二季度相比，收入增長了 23%，按固定匯率計算增長了 20%。這一業績完全是由 22 個百分點的銷量增長推動的。正如之前在 2020 年第二季度所強調的那樣，我們看到 2020 年第一季度發生的 2.5 億美元與大流行相關的產品庫存出現逆轉。如果不包括 COVID-19 抗體收入，2020 年第二季度與 COVID-19 相關的去庫存和 Cialis 在中國，我們的核心業務在本季度增長了 12%，高於第一季度的 7%。

We were pleased to see sequential top line growth in the core business this quarter, signaling that health care systems' continued recovery from the pandemic and the strength of our underlying business. Key growth products continue to drive our revenue growth and represent 54% of our core business this quarter.

我們很高興看到本季度核心業務的收入連續增長，這表明醫療保健系統從大流行中持續復甦以及我們基礎業務的實力。關鍵增長產品繼續推動我們的收入增長，佔本季度核心業務的 54%。

Our non-GAAP gross margin was 79.3% in Q2 or 79.7%, excluding impact of foreign exchange on international inventories sold. Excluding the FX impact, our gross margin increased by approximately 60 basis points compared to last year. Our non-GAAP operating margin was 29.4%, representing an improvement of nearly 140 basis points. We are pleased to see operating margin expand year-over-year, and we expect continued expansion in the second half of this year.

我們第二季度的非美國通用會計準則毛利率為 79.3% 或 79.7%，不包括外匯對已售國際庫存的影響。排除外匯影響，我們的毛利率與去年相比增加了約 60 個基點。我們的非美國通用會計準則營業利潤率為 29.4%，提高了近 140 個基點。我們很高興看到營業利潤率同比增長，我們預計今年下半年將繼續擴張。

On the pipeline front, we achieved multiple milestones since our earnings call in April, including: receiving Breakthrough Therapy Designation for donanemab and announcing our plan to submit to the FDA under the accelerated approval pathway; announcing positive Phase III results for tirzepatide's SURPASS-4 trial with planned global submissions of the SURPASS program for tirzepatide in type 2 diabetes by the end of 2021; obtaining approval for Jardiance in partnership with Boehringer Ingelheim for HFrEF in Europe and announcing positive Phase III results from the EMPEROR-Preserved trial for Jardiance in HFpEF, the first and only successful trial for this patient population; and initiating Phase III trial results for pirtobrutinib in mantle cell lymphoma, tirzepatide in HFpEF, and Verzenio in HR+ HER2+ early breast cancer and now prostate cancer.

在管道方面，自 4 月份的財報電話會議以來，我們實現了多個里程碑，包括：獲得多納奈馬的突破性治療指定，並宣布我們計劃根據加速批准途徑提交給 FDA；宣布 tirzepatide 的 SURPASS-4 試驗的 III 期陽性結果，併計劃在 2021 年底之前在全球提交用於 tirzepatide 治療 2 型糖尿病的 SURPASS 項目； Jardiance 與勃林格殷格翰合作在歐洲獲得 HFrEF 的批准，並宣布 EMPEROR-Preserved 的 HFpEF 中 Jardiance 試驗的 III 期陽性結果，這是針對該患者群體的第一個也是唯一成功的試驗；並啟動 pirtobrutinib 治療套細胞淋巴瘤、tirzepatide 治療 HFpEF 和 Verzenio 治療 HR+ HER2+ 早期乳腺癌和現在的前列腺癌的 III 期試驗結果。

We also continue to augment our pipeline with business development deals and announced the acquisition of Protomer Technologies. We welcome the Protomer team to Lilly and are excited to bring this technology to our diabetes pipeline as we believe glucose-sensing insulin may become the next generation for insulin treatment to improve the quality of life for people living with diabetes. Lastly, on financials, we returned approximately $1.3 billion to shareholders via the dividend and share repurchases in the quarter and authorized the repurchase of up to $5 billion in stock in addition to the $500 million authorization remaining under our 2018 share repurchase program.

我們還繼續通過業務開發交易擴大我們的管道，並宣布收購 Protomer Technologies。我們歡迎 Protomer 團隊加入禮來，並很高興將這項技術引入我們的糖尿病管道，因為我們相信葡萄糖感應胰島素可能成為下一代胰島素治療，以改善糖尿病患者的生活質量。最後，在財務方面，我們在本季度通過股息和股票回購向股東返還了大約 13 億美元，並授權回購高達 50 億美元的股票，此外還有 2018 年股票回購計劃下剩餘的 5 億美元授權。

Moving on to Slides 5 and 6. You'll see a list of key events since our Q1 earnings call, including a May webcast, which highlighted our updated environmental, social and governance strategy and our sustainability efforts as well as the launch of a new ESG website to serve as a comprehensive resource to provide increased transparency regarding the company's ESG goals and progress.

轉到幻燈片 5 和 6。您將看到自我們第一季度財報電話會議以來的重要事件列表，包括 5 月的網絡廣播，其中重點介紹了我們更新的環境、社會和治理戰略以及我們的可持續發展努力，以及推出新的ESG 網站作為綜合資源，可提高公司 ESG 目標和進展的透明度。

Further, as part of our goal to become carbon-neutral in our own operations at our manufacturing plant in Kinsale, we recently inaugurated a new solar field, which is now the largest in Ireland. We also announced donations of COVID-19 therapies at no cost to low income and lower middle income countries heavily impacted by the pandemic and are proud of the impacts we are having around the world as we work to combat COVID-19.

此外，作為我們在金塞爾製造工廠實現自身運營中碳中和目標的一部分，我們最近開設了一個新的太陽能場，該場現在是愛爾蘭最大的。我們還宣布向受大流行嚴重影響的低收入和中低收入國家免費捐贈 COVID-19 療法，並為我們在努力抗擊 COVID-19 時在世界各地產生的影響感到自豪。

Now I'll turn the call over to Anat to review our Q2 results and to provide an update on our financial guidance for 2021.

現在，我將把電話轉給 Anat，以審查我們的第二季度業績，並提供我們 2021 年財務指導的最新信息。

Thanks, Dave. Slides 7 and 8 summarize financial performance in the second quarter and year-to-date. I'll focus my comments on non-GAAP performance.

謝謝，戴夫。幻燈片 7 和 8 總結了第二季度和年初至今的財務業績。我將把我的評論集中在非公認會計原則的表現上。

Revenue increased 23% this quarter compared to Q2 2020 or 12% excluding the items Dave mentioned earlier, representing strong momentum for our core business. Given the COVID-19-related stocking and destocking seen between Q1 and Q2 2020, our first half performance of 11% revenue growth or 8% in constant currency, excluding COVID-19 antibody revenue, is a more accurate reflection of underlying performance. And the sequential quarter-over-quarter revenue growth better represented strength in our core business. Sequential revenue growth from Q1 to Q2 for our core business, increase in vaccination rates in many major markets and the majority of our sales reps now being back in the field suggest a recovery from the pandemic was in line with our expectation for the quarter.

與 2020 年第二季度相比，本季度的收入增長了 23%，或者不包括 Dave 前面提到的項目，增長了 12%，這代表了我們核心業務的強勁勢頭。鑑於在 2020 年第一季度和第二季度之間出現了與 COVID-19 相關的庫存和去庫存，我們上半年收入增長 11% 或按固定匯率計算 8%（不包括 COVID-19 抗體收入）的表現更準確地反映了潛在業績。季度環比收入增長更好地代表了我們核心業務的實力。我們的核心業務從第一季度到第二季度的收入連續增長，許多主要市場的疫苗接種率增加，以及我們的大多數銷售代表現在重返現場，這表明從大流行中復蘇符合我們對本季度的預期。

We're particularly pleased with the strong volume growth across key brands like Trulicity, Taltz, Verzenio and Jardiance. Verzenio in the U.S. grew nearly 6 percentage points in share total prescription exiting June compared to the prior year, while Trulicity, Taltz and Jardiance increased their leading market share in the same period while class growth accelerated. These products, along with other key growth products, represented 54% of revenue in the core business this quarter. Gross margin as a percent of revenue declined 30 basis points to 79.3% in Q2. The decrease in gross margin percent was driven primarily by unfavorable effect of foreign exchange rates on international inventories sold. Excluding this FX impact, gross margin as a percent of revenue grew 60 points this quarter.

我們對 Trulicity、Taltz、Verzenio 和 Jardiance 等主要品牌的強勁銷量增長感到特別高興。與去年相比，美國 Verzenio 在 6 月份的總處方份額增長了近 6 個百分點，而 Trulicity、Taltz 和 Jardiance 在同一時期增加了領先的市場份額，同時類別增長加速。這些產品以及其他關鍵增長產品佔本季度核心業務收入的 54%。第二季度毛利率佔收入的百分比下降了 30 個基點至 79.3%。毛利率下降的主要原因是匯率對國際銷售庫存的不利影響。排除這種外匯影響，本季度毛利率佔收入的百分比增長了 60 個百分點。

Total operating expenses grew 18% this quarter compared to the same quarter last year. Marketing, selling and administrative expenses increased 16% as the base period in Q2 2020 included a meaningful reduction in direct-to-consumer marketing and customer-facing expenses as health care systems closed. R&D expenses increased 20%, driven by investment in exciting late-stage pipeline opportunities, including pirtobrutinib, tirzepatide, donanemab and lebrikizumab. In Q2, we also invested approximately $85 million in COVID therapies' R&D, bringing our total COVID-19 R&D investment to approximately $300 million year-to-date. Net of COVID-19 R&D investment, operating expense growth was 18% compared to Q2 of 2020 and 10% for the first half of the year.

與去年同期相比，本季度總運營費用增長了 18%。營銷、銷售和管理費用增長了 16%，因為 2020 年第二季度的基期包括隨著醫療保健系統關閉而顯著減少直接面向消費者的營銷和麵向客戶的費用。研發費用增長了 20%，這得益於對激動人心的後期管道機會的投資，包括 pirtobrutinib、tirzepatide、donanemab 和 lebrikizumab。在第二季度，我們還在 COVID 療法的研發上投資了約 8500 萬美元，使我們的 COVID-19 研發總投資達到約 3 億美元。扣除 COVID-19 研發投資後，運營費用較 2020 年第二季度增長 18%，上半年增長 10%。

Operating income increased 29% compared to Q2 of 2020 and operating income as a percent of revenue was 29.4% for the quarter, an increase of 140 basis points compared to the prior year. This increase was driven by revenue growth outpacing expense growth. And we expect continued margin expansion in the second half of 2021. Other income and expense was income of $5 million this quarter compared to expense of $57 million in Q2 2020, driven by income from European patent settlements for Alimta.

與 2020 年第二季度相比，營業收入增長了 29%，本季度營業收入佔收入的百分比為 29.4%，與去年同期相比增加了 140 個基點。這一增長是由收入增長超過費用增長推動的。我們預計 2021 年下半年利潤率將繼續擴大。本季度其他收入和支出為 500 萬美元，而 2020 年第二季度的支出為 5700 萬美元，這主要是受 Alimta 歐洲專利和解收入的推動。

Our effective tax rate was 14.4%, an increase of 350 basis points compared with the same quarter last year. The effective tax rate for both periods were reduced by net discrete tax benefits with the lower net discrete tax benefit reflected in the second quarter of 2021. At the bottom line, net income and earnings per share increased 29% in Q2 and 22% year-to-date, or 30% and 24%, respectively, in constant currency.

我們的有效稅率為14.4%，與去年同期相比增加了350個基點。兩個時期的有效稅率因淨離散稅收優惠而降低，2021 年第二季度反映的淨離散稅收優惠較低。最重要的是，第二季度的淨收入和每股收益增長了 29%，全年增長了 22%。迄今為止，按固定匯率計算，分別為 30% 和 24%。

On Slide 9, we quantify the effect of price, rate and volume on revenue growth across the world. And we are encouraged by the growth seen across most of our major geographies. This quarter, U.S. revenue grew 18% compared to the second quarter of 2020. Adjusting for COVID-19 antibody revenue and the Q2 2020 COVID-19-related destocking, the core business grew 8% in the U.S., up from 5% in Q1 on that same basis. These results were driven entirely by volume, led by Trulicity, Taltz, Verzenio and Jardiance.

在幻燈片 9 中，我們量化了價格、費率和數量對全球收入增長的影響。我們對我們大多數主要地區的增長感到鼓舞。本季度，美國收入與 2020 年第二季度相比增長 18%。根據 COVID-19 抗體收入和 2020 年第二季度與 COVID-19 相關的去庫存調整，美國的核心業務增長 8%，高於第一季度的 5%在同樣的基礎上。這些結果完全由數量驅動，由 Trulicity、Taltz、Verzenio 和 Jardiance 領導。

Pricing was a 1% drag on U.S. revenue growth this quarter with increased rebates to maintain excellent access and higher growth in lower net price segments, largely offset by lower utilization in the 340B segment, changes for estimates to rebates and discounts and, to a lesser extent, modest list price increases. The year-to-date price decline of 3% in the U.S. is in line with our net price expectations for the full year.

定價對本季度美國收入增長造成 1% 的拖累，原因是增加了回扣以保持良好的准入以及較低淨價格段的更高增長，這在很大程度上被 340B 段的利用率降低、回扣和折扣估計的變化以及較小的程度，適度的標價上漲。美國今年迄今價格下跌 3%，符合我們全年的淨價格預期。

Specific to Taltz in the U.S. Performance for the quarter was in line with the expectations we described on the Q1 earnings call. And we are pleased to see a return to net sales growth this quarter as volume gains more than offset price declines. Taltz Q2 performance benefited from a favorable change to prior estimates for rebates and discounts and COVID-19-related inventory destocking last year. Excluding these items, Taltz still returned to double-digit growth in the second quarter.

具體到 Taltz 在美國的季度業績符合我們在第一季度財報電話會議上描述的預期。我們很高興看到本季度淨銷售額恢復增長，因為銷量增長超過了價格下降。 Taltz 第二季度的業績得益於去年對折扣和折扣以及與 COVID-19 相關的庫存去庫存的先前估計的有利變化。剔除這些項目，Taltz 在第二季度仍恢復了兩位數的增長。

We believe the net price decline for Taltz in the first half of 2021 represents the underlying full price trend and that continued volume growth will drive net sales acceleration in the second half of the year. While mid-term price trends are currently stable, given increasing variability in peer mix, we continue to expect quarterly variability in reported U.S. net price changes across our business.

我們認為，2021 年上半年 Taltz 的淨價下跌代表了潛在的全價趨勢，持續的銷量增長將推動下半年的淨銷售加速。雖然中期價格趨勢目前是穩定的，但鑑於同行組合的可變性越來越大，我們繼續預計我們業務中報告的美國淨價格變化的季度變化。

Moving to Europe. Revenue grew 27% in constant currency. Excluding COVID-19 antibody revenue and the negative impact of Q2 2020 COVID-19-related customer buying patterns, revenue grew 14% in constant currency, driven entirely by volume growth primarily for Trulicity, Taltz, Alimta and Olumiant. We continue to be pleased with the momentum of our business in Europe and expect continued growth in the second half of this year, excluding the expected impact from the loss of exclusivity for Alimta.

搬到歐洲。按固定匯率計算，收入增長了 27%。排除 COVID-19 抗體收入和 2020 年第二季度 COVID-19 相關客戶購買模式的負面影響，收入增長 14%（按固定匯率計算），這完全是由 Trulicity、Taltz、Alimta 和 Oluminant 的銷量增長推動的。我們繼續對我們在歐洲的業務發展勢頭感到滿意，並預計今年下半年將繼續增長，不包括失去 Alimta 獨家經營權的預期影響。

In Japan, revenue grew 2% in constant currency, driven primarily by the launches of Olumiant and Emgality. Revenue growth in Japan continues to be negatively impacted by the decreased demand for several products that have lost market exclusivity. But our key growth products grew 21% in Q2 in Japan and represented approximately 50% of the business there. Recent surges of COVID-19 cases continue to negatively impact recovery in Japan, but we currently expect improved revenue growth in the second half of the year based on the uptake of newer products.

在日本，以固定匯率計算的收入增長了 2%，主要是受推出 Oluminant 和 Emgality 的推動。日本的收入增長繼續受到對失去市場獨占性的幾種產品的需求下降的負面影響。但我們的主要增長產品在日本第二季度增長了 21%，約佔該地區業務的 50%。最近 COVID-19 病例激增繼續對日本的複蘇產生負面影響，但我們目前預計，基於新產品的採用，下半年的收入增長將有所改善。

In China, revenue grew 106% in constant currency, primarily driven by the divestiture of Cialis and the launches of Tyvyt and Trulicity. Excluding the impact from the Cialis transaction, our revenue in China grew 35% in constant currency. We are excited about the continued momentum in China as sales of new medicines have accelerated significantly in the past 3 quarters. Revenue in the rest of the world increased 5% in constant currency, driven primarily by our key growth products. At the bottom of the slide is the price/rate/volume effect on revenue for our June year-to-date results, which shows double-digit growth across all major geographies, except Japan.

在中國，按固定匯率計算，收入增長了 106%，這主要得益於 Cialis 的剝離以及 Tyvyt 和 Trulicity 的推出。排除 Cialis 交易的影響，我們在中國的收入按固定匯率計算增長了 35%。我們對中國的持續發展勢頭感到興奮，因為新藥的銷售在過去三個季度顯著加速。世界其他地區的收入按固定匯率計算增長了 5%，主要受我們主要增長產品的推動。幻燈片底部是我們 6 月份年初至今業績的價格/費率/銷量對收入的影響，顯示除日本以外的所有主要地區都有兩位數的增長。

As shown on Slide 10, our key growth products continue to drive strong worldwide volume growth. These products drove nearly 17 percentage points of growth this quarter and continue to drive our overall performance and outlook.

如幻燈片 10 所示，我們的主要增長產品繼續推動全球銷量的強勁增長。這些產品在本季度推動了近 17 個百分點的增長，並繼續推動我們的整體業績和前景。

Slide 11 highlights the contributions of our key growth products. In total, these brands generated over $3.5 billion in revenue this quarter and made up 54% of our core business revenue in Q2. We're encouraged by the strength of our key products in Q2, collectively up over 34% compared to the same period last year. Trulicity, Taltz, Verzenio and Jardiance all continue to outgrow their respective classes. We are now tracking above pre-COVID-19 new-to-brand prescription baseline in the U.S. across all major therapeutic areas with the exception of oncology and the CGRP antibody class, which we expect will continue to recover in the second half of the year.

幻燈片 11 突出了我們主要增長產品的貢獻。這些品牌本季度的總收入超過 35 億美元，占我們第二季度核心業務收入的 54%。我們對第二季度主要產品的實力感到鼓舞，與去年同期相比，整體增長超過 34%。 Trulicity、Taltz、Verzenio 和 Jardiance 都繼續超過各自的班級。除了腫瘤學和 CGRP 抗體類別外，我們現在在美國所有主要治療領域都在追踪 COVID-19 之前的新品牌處方基線以上，我們預計這些領域將在下半年繼續恢復.

On Slide 12, we provide an update on capital allocation. In the first half of 2021, we invested $5 billion to drive our future growth through a combination of after-tax investments in R&D, business development and capital investments. In addition, we returned over $1.5 billion to shareholders in dividend and [$500 million in](added by company after call) share repurchase. As we look ahead to the second half of the year, we will continue to fund our growth of our key products and recent launches, invest in our pipeline and seek external innovation to augment our future prospects as well as returning capital to shareholders.

在幻燈片 12 中，我們提供了資本配置的最新信息。 2021 年上半年，我們投資了 50 億美元，通過對研發、業務發展和資本投資的稅後投資相結合來推動我們的未來增長。此外，我們向股東返還了超過 15 億美元的股息和 [5 億美元]（由公司在電話會議後添加）股票回購。展望下半年，我們將繼續為我們的主要產品和近期發布的增長提供資金，投資我們的管道並尋求外部創新以擴大我們的未來前景以及向股東返還資本。

Turning to our 2021 financial guidance on Slide 13. We are updating our GAAP and non-GAAP guidance. While the COVID-19 pandemic is still impacting countries around the world, the pace of recovery from the pandemic was in line with our expectations in Q2. New-to-brand scripts in most of the classes in which we compete with are tracking above pre-COVID baseline in the U.S. and health care systems in most major markets are largely returning to normal as we enter the second half of 2021.

轉到幻燈片 13 上的 2021 年財務指導。我們正在更新我們的 GAAP 和非 GAAP 指導。儘管 COVID-19 大流行仍在影響世界各國，但從大流行中恢復的步伐符合我們在第二季度的預期。進入 2021 年下半年，我們競爭的大多數類別中的新品牌腳本都在美國的 COVID 之前的基線之上跟踪，並且大多數主要市場的醫療保健系統正在基本恢復正常。

We are increasing our full year revenue outlook for the core business by $200 million to reflect the strong performance and favorable impact from foreign exchange. We are, however, lowering the top end of the range for COVID-19 antibody revenue by $400 million and confirming the bottom end of that range. Moving forward, we expect COVID-19 antibody revenues to be less of a factor as demonstrated by Q2 revenue declining to $150 million from $810 million in Q1. As variants are growing, we recognize the situations across the globe can evolve quickly and we plan to adapt as required. The net impact of these changes is an updated revenue range of $26.8 million to $27.4 billion.

我們將核心業務的全年收入預期提高 2 億美元，以反映強勁的業績和外彙的有利影響。然而，我們將 COVID-19 抗體收入範圍的上限降低了 4 億美元，並確認了該範圍的下限。展望未來，我們預計 COVID-19 抗體收入將不再是一個因素，正如第二季度收入從第一季度的 8.1 億美元下降至 1.5 億美元所證明的那樣。隨著變體的不斷增加，我們認識到全球形勢可能會迅速發展，我們計劃根據需要進行調整。這些變化的淨影響是更新後的收入範圍為 2680 萬美元至 274 億美元。

Our outlook for non-GAAP gross margin percent remains unchanged at approximately 79%. On a reported basis, we've lowered guidance for gross margin percent to approximately 75% to reflect the impact of COVID-19 antibodies excess inventory charge due to the combination of changes to current and forecasted demand from the U.S. and international governments and near-term expiry of COVID-19 antibodies inventory. For research and development and SG&A, our guidance ranges remain unchanged. However, investment in promising R&D opportunities and exciting potential launches could push us towards the top end of our guidance range for both R&D and SG&A.

我們對非公認會計原則毛利率百分比的展望保持不變，約為 79%。據報導，我們已將毛利率百分比的指導下調至約 75%，以反映 COVID-19 抗體超額庫存費用的影響，原因是美國和國際政府當前和預測需求的變化以及近乎COVID-19 抗體庫存的期限屆滿。對於研發和 SG&A，我們的指導範圍保持不變。然而，對有前景的研發機會和令人興奮的潛在發布的投資可能會將我們推向研發和 SG&A 指導範圍的高端。

Our non-GAAP operating margin guidance is now expected to be approximately 30%, driven by lower COVID-19 antibody revenue. However, it remains approximately 31%, excluding COVID-19 antibodies. Our GAAP operating margin is now expected to be approximately 24%. We are increasing our non-GAAP range for OID to an expense of 0 to $100 million to reflect the Alimta patent settlements in Europe I noted earlier. And our GAAP range is now income of $375 million to $475 million, which also reflects the impact of equity investment gains in the first half of the year.

由於 COVID-19 抗體收入下降，我們的非公認會計原則營業利潤率指導現在預計約為 30%。但是，不包括 COVID-19 抗體，它仍然約為 31%。我們的 GAAP 營業利潤率現在預計約為 24%。我們正在將 OID 的非 GAAP 範圍擴大到 0 到 1 億美元，以反映我之前提到的 Alimta 在歐洲的專利和解。而我們的GAAP範圍現在是3.75億美元到4.75億美元的收入，這也反映了上半年股權投資收益的影響。

On a non-GAAP basis, our expected tax rate remains unchanged. And on a reported basis, we've lowered our expected tax rate to approximately 12%. Finally, the non-GAAP range for earnings per share remains unchanged at $7.80 to $8 while GAAP EPS is expected to be in the range of $6.73 to $6.93, primarily driven by the impact of the COVID-19 antibody inventory charge, the impact of equity investment gains and the Alimta patent settlements in Europe.

在非公認會計原則的基礎上，我們的預期稅率保持不變。根據報告，我們已將預期稅率降低至約 12%。最後，非 GAAP 每股收益範圍保持不變，為 7.80 美元至 8 美元，而 GAAP 每股收益預計在 6.73 美元至 6.93 美元之間，主要受 COVID-19 抗體庫存費用的影響、股權的影響投資收益和 Alimta 在歐洲的專利和解。

We are confident in our ability to achieve our 2021 revenue goals for the core business while delivering mid-teens EPS growth. As we look at the underlying volume and share trends across our key growth products, we're confident in our full year outlook for the core business. And the pipeline successes in the first half of this year strengthen our conviction in our mid-term and long-term outlook for continued top-tier revenue growth and operating margin expansion.

我們有信心實現核心業務的 2021 年收入目標，同時實現 10 年左右的每股收益增長。當我們審視我們主要增長產品的潛在銷量和分享趨勢時，我們對核心業務的全年前景充滿信心。今年上半年管道的成功加強了我們對持續頂級收入增長和營業利潤率擴張的中長期前景的信念。

Now I will turn the call over to Dan to provide an update on our pipeline.

現在我將把電話轉給 Dan，以提供有關我們管道的更新。

Thanks, Anat. 2021 has clearly been a productive year for R&D at Lilly with continued strong progress in our pipeline and more potential catalysts on the way. Before I get into the broader portfolio update, I'll spend a few minutes highlighting several updates for our late-stage pipeline.

謝謝，阿納特。 2021 年顯然是禮來公司研發的豐收年，我們的研發管線繼續取得強勁進展，更多潛在催化劑也在醞釀之中。在進入更廣泛的產品組合更新之前，我將花幾分鐘重點介紹我們後期管道的幾個更新。

I'll start with donanemab. In Q2, the first amyloid lowering agent for the treatment of Alzheimer's disease was approved under the FDA's accelerated approval pathway based on plaque lowering, which we believe reflects a shift in policy and sets a new path for Alzheimer's drug approval in the U.S. Lilly has long been an advocate for using biomarkers for amyloid plaque and neurofibrillary tangles to identify patients for treatment and to monitor their response to therapy. We were pleased to see the FDA's conclusion that improvements in brain pathology are appropriate surrogates for clinical efficacy of Alzheimer's drugs.

我將從 donanemab 開始。在第二季度，第一個治療阿爾茨海默病的澱粉樣蛋白降低劑在 FDA 基於斑塊降低的加速批准途徑下獲得批准，我們認為這反映了政策的轉變，並為美國阿爾茨海默病藥物的批准開闢了一條新道路。禮來長期以來一直倡導使用澱粉樣斑塊和神經原纖維纏結的生物標誌物來識別患者進行治療並監測他們對治療的反應。我們很高興看到 FDA 的結論，即腦病理學的改善是阿爾茨海默病藥物臨床療效的適當替代物。

Based on data we've seen to date, we believe donanemab clears plaque faster and deeper than previously seen with other therapies and achieved complete plaque clearance in a majority of patients in TRAILBLAZER-ALZ after only limited duration of dosing. On the basis of the clinical evidence for donanemab, we were pleased to have received Breakthrough Therapy Designation from the FDA. At the Alzheimer's Association International Conference last week, we shared additional important analyses from donanemab TRAILBLAZER-ALZ. Briefly, I'll highlight several findings.

根據我們迄今為止看到的數據，我們相信多納奈馬比以前用其他療法看到的更快、更深地清除斑塊，並且在 TRAILBLAZER-ALZ 的大多數患者中，僅在有限的給藥時間後就實現了完全的斑塊清除。基於多那奈單抗的臨床證據，我們很高興獲得了 FDA 的突破性治療指定。在上週的阿爾茨海默氏症協會國際會議上，我們分享了來自 donanemab TRAILBLAZER-ALZ 的其他重要分析。簡而言之，我將重點介紹幾個發現。

First, we shared detailed exploratory statistical analyses comparing a variety of methods beyond MMRM and DPM, as summarized on Slide 14. We are pleased to see that these new analyses showed consistency of effects on primary and secondary outcomes across all statistical methods. Notably, all of the new analyses conducted showed good separation of treatment from placebo with statistical significance achieved for most endpoints at nearly all relevant time points measured.

首先，我們分享了詳細的探索性統計分析，比較了 MMRM 和 DPM 之外的各種方法，如幻燈片 14 所示。我們很高興地看到，這些新分析顯示所有統計方法對主要和次要結果的影響具有一致性。值得注意的是，進行的所有新分析都顯示治療與安慰劑的良好分離，在幾乎所有測量的相關時間點，大多數終點都達到了統計學顯著性。

The robustness of the treatment efficacy across analytical methods increases our confidence in the potential clinical benefit of donanemab. While all statistical methods evaluated showed similar results, we note that the Bayesian disease progression model, DPM, closely reflected the raw observed data with the smallest standard error of any method. These results reinforce our hypothesis that DPM is a preferred analytical method for Alzheimer's trials.

跨分析方法的治療效果的穩健性增加了我們對多納奈單抗潛在臨床益處的信心。雖然評估的所有統計方法都顯示出相似的結果，但我們注意到貝葉斯疾病進展模型 DPM 以任何方法中最小的標準誤差密切反映了原始觀察數據。這些結果強化了我們的假設，即 DPM 是阿爾茨海默病試驗的首選分析方法。

Additionally, we shared new data showing a relationship of amyloid plaque reduction and slowing of cognitive decline, as shown on Slide 15. To our knowledge, this is the first time such results have been available. When we initially reported the results of TRAILBLAZER-ALZ, we commented that at a group level, patients treated with donanemab showed both statistically better plaque reduction and statistically better slowing of cognitive decline at 18 months. But patient-level correlations between degree of plaque reduction and magnitude of slowing of cognitive decline were not significant.

此外，如幻燈片 15 所示，我們分享了顯示澱粉樣斑塊減少和認知衰退減緩之間關係的新數據。據我們所知，這是第一次獲得此類結果。當我們最初報告 TRAILBLAZER-ALZ 的結果時，我們評論說，在組水平上，接受 donanemab 治療的患者在 18 個月時顯示出統計學上更好的斑塊減少和統計學上更好的認知衰退減緩。但斑塊減少程度與認知衰退減緩幅度之間的患者水平相關性並不顯著。

Now using a more sophisticated PK/PET/iADRS exploratory analysis that uses all of the available time course data, we showed a highly significant relationship between degree of amyloid plaque reduction and slowing of cognitive decline with p less than 0.001. The Conrado model, shown here, was published in 2014 and is the result of efforts from the Coalition Against Major Diseases, CAMD, which collected placebo data from 15 randomized trials, including almost 4,500 participants.

現在使用更複雜的 PK/PET/iADRS 探索性分析，使用所有可用的時間過程數據，我們顯示澱粉樣斑塊減少程度與認知衰退減緩之間存在高度顯著的關係，p 小於 0.001。此處顯示的 Conrado 模型於 2014 年發布，是抗主要疾病聯盟 (CAMD) 努力的結果，該聯盟從 15 項隨機試驗中收集了安慰劑數據，其中包括近 4,500 名參與者。

We introduced a treatment arm and incorporated percent amyloid plaque removal into this model to generate these results. And we believe this is important support for the use of amyloid plaque reduction as a surrogate for clinical efficacy. Notably, these data suggests that full clearance of amyloid plaque is required for highest efficacy as model results predict that patients achieving 100% clearance of amyloid plaque could have more than 40% slowing of disease progression.

我們引入了一個治療組，並將澱粉樣斑塊去除率納入該模型以產生這些結果。我們相信這是使用澱粉樣斑塊減少作為臨床療效替代指標的重要支持。值得注意的是，這些數據表明澱粉樣斑塊的完全清除是最高療效所必需的，因為模型結果預測，達到 100% 清除澱粉樣斑塊的患者可能會減緩超過 40% 的疾病進展。

Moving to Slide 16. We show an exploratory analysis looking at the effect of donanemab's plaque clearance on development of tau pathology. Tau pathology is an exciting biomarker since measures of Alzheimer's disease tau, unlike measures of amyloid plaque, have been correlated with clinical measures of cognitive and functional decline as noted here. Importantly, we have previously shown that donanemab-treated patients had slower accumulation of regional brain tau pathology than placebo-treated patients. This is an important finding because the amount of brain tau pathology is an excellent predictor of subsequent cognitive decline, a finding we observed with solanezumab in EXPEDITION3 and reproduced once again in TRAILBLAZER-ALZ.

轉到幻燈片 16。我們展示了一項探索性分析，觀察多那奈單抗的斑塊清除對 tau 病理學發展的影響。 Tau 病理學是一個令人興奮的生物標誌物，因為阿爾茨海默病 tau 的測量與澱粉樣斑塊的測量不同，與此處所述的認知和功能衰退的臨床測量相關。重要的是，我們之前已經表明，與安慰劑治療的患者相比，接受 donanemab 治療的患者局部腦 tau 病理的積累較慢。這是一個重要的發現，因為腦 tau 病變的數量是隨後認知能力下降的一個很好的預測指標，我們在 EXPEDITION3 中用 solanezumab 觀察到了這一發現，並在 TRAILBLAZER-ALZ 中再次重現。

Now we've extended these results to show that the donanemab-treated patients who achieved complete clearance of amyloid plaque by 6 months had the most marked slowing of tau spread with nearly complete abrogation of progression of frontal lobe. This reinforces our hypothesis that both deep and rapid amyloid plaque clearance are required for optimal drug efficacy. With this new data we presented last week, we have now linked degree of amyloid plaque reduction with degree of clinical benefit as well as degree of amyloid plaque reduction with degree of benefit on brain tau pathology, which is itself linked to clinical benefit.

現在我們擴展了這些結果，以表明在 6 個月內完全清除澱粉樣蛋白斑塊的接受多奈奈單抗治療的患者俱有最顯著的 tau 擴散減慢，幾乎完全消除了額葉的進展。這強化了我們的假設，即深度和快速的澱粉樣蛋白斑塊清除是最佳藥物療效所必需的。根據我們上週提供的這些新數據，我們現在將澱粉樣蛋白斑塊減少程度與臨床益處程度以及澱粉樣蛋白斑塊減少程度與對腦 tau 病理學的益處程度聯繫起來，這本身與臨床益處相關。

As displayed on Slide 17, we have just recently obtained data with our plasma tau biomarker, phospho-tau217. These new data demonstrate that amyloid plaque clearance with donanemab also resulted in reversal of the typical increases of phosphorylated tau seen in the blood with decreases from baseline of more than 24% and a change from the untreated arm with a p-value of less than 0.0001. This highly significant effect was seen as early as 3 months following initiation of treatment and could reflect a combination of less tau spread in the brain as well as less neuronal damage, which could account for tau leakage into the periphery.

如幻燈片 17 所示，我們最近剛剛獲得了血漿 tau 生物標誌物 phospho-tau217 的數據。這些新數據表明，用多那奈單抗清除澱粉樣蛋白斑塊還可以逆轉血液中磷酸化 tau 的典型增加，從基線下降超過 24%，與未治療組相比，p 值小於 0.0001 .這種非常顯著的效果早在開始治療後 3 個月就被觀察到，這可能反映了大腦中 tau 擴散較少以及神經元損傷較少的組合，這可能是 tau 洩漏到外周的原因。

You can see on the right side of the slide that the effect on plasma tau is also correlated to a degree of plaque reduction with nearly every patient on treatment who achieved substantial plaque clearance showing flat or declining plasma phospho-tau. We are delighted to see the potential utility of P-tau217 not just for diagnosing disease but also for monitoring treatment efficacy. We believe this could be another important contribution to the Alzheimer's field.

您可以在幻燈片的右側看到，對血漿 tau 的影響也與斑塊減少的程度相關，幾乎每個接受治療的患者都獲得了顯著的斑塊清除，顯示出平坦或下降的血漿磷酸化 tau。我們很高興看到 P-tau217 不僅可以用於診斷疾病，還可以用於監測治療效果。我們相信這可能是對阿爾茨海默病領域的又一重要貢獻。

Finally, on Slide 18, the significant relationship between plasma P-tau217 reduction and the slowing of cognitive decline is shown. This additional biomarker for efficacy links the donanemab mechanism of amyloid plaque clearance with positive effects on both clinical outcomes and tau pathology. These data suggest that patients who achieved a 30% decrease in P-tau217 from baseline showed more than 40% slowing of disease progression.

最後，在幻燈片 18 上，顯示了血漿 P-tau217 減少與認知衰退減緩之間的顯著關係。這種額外的療效生物標誌物將多納尼單抗清除澱粉樣蛋白斑塊的機制與對臨床結果和 tau 病理學的積極影響聯繫起來。這些數據表明，與基線相比，P-tau217 降低 30% 的患者表現出超過 40% 的疾病進展減緩。

The three main findings I just discussed: one, the consistency of clinical benefit across statistical methods; two, the correlation of plaque lowering the clinical benefit of patients who achieved the greatest plaque clearance having the greatest opportunity for benefit; and three, the correlation between achieving complete plaque clearance and beneficial effects on tau pathology seen in the brain and measured in the periphery, which themselves are predictors for clinical benefit, strongly support the efficacy of donanemab and give us confidence that the remarkable levels of amyloid plaque clearance achieved by donanemab could translate into a meaningful breakthrough for patients.

我剛才討論的三個主要發現：一，不同統計方法臨床獲益的一致性；二，斑塊降低患者的臨床益處的相關性，獲得最大斑塊清除率的患者受益機會最大；第三，實現完全清除斑塊和對大腦中觀察到的和在外周測量的 tau 病理學的有益影響之間的相關性，它們本身就是臨床益處的預測因子，強烈支持多納奈單抗的功效，並讓我們相信澱粉樣蛋白的顯著水平donanemab 實現的斑塊清除可以轉化為對患者有意義的突破。

Moving to Slide 19. Accordingly, we've announced that we plan to submit to the FDA under the accelerated approval pathway before the end of this year based on data from completed studies, supplemented by additional safety data from the ongoing TRAILBLAZER-ALZ 2 study. We remain focused on enrolling TRAILBLAZER-2 with the aim to replicate the positive results of TRAILBLAZER-1. Replication is important to overcome skepticism in the field. We hope that TRAILBLAZER-ALZ 2 will generate important confirmatory data for patients, physicians and payers and help us understand how to make sure the right patient gets the right duration of therapy at the right stage of disease.

轉到幻燈片 19。因此，我們宣布，我們計劃在今年年底之前根據已完成研究的數據，並輔以正在進行的 TRAILBLAZER-ALZ 2 研究的額外安全數據，以加速批准途徑向 FDA 提交.我們仍然專注於招募 TRAILBLAZER-2，目的是複制 TRAILBLAZER-1 的積極結果。複製對於克服該領域的懷疑很重要。我們希望 TRAILBLAZER-ALZ 2 將為患者、醫生和付款人生成重要的確認數據，並幫助我們了解如何確保正確的患者在正確的疾病階段獲得正確的治療時間。

We are pleased to announce today that we have closed screening for TRAILBLAZER-ALZ 2 with an adequate number of subjects now in the trial's screening process to fully enroll the study. Given that conducting and processing and imaging studies used during screening take several weeks to complete, we expect that the final subject to complete screening procedures and receive their first dose of donanemab or placebo by the end of the third quarter and the study will complete 18 months later. Given this progress in enrollment, we are confident that we will achieve the number and duration of drug exposures needed to appropriately characterize the safety profile of donanemab, allowing for regulatory submission by the end of this year. Discussions with the FDA are consistent with our prior statement supporting a submission before the end of 2021.

我們今天很高興地宣布，我們已經結束了對 TRAILBLAZER-ALZ 2 的篩選，現在有足夠數量的受試者處於試驗篩選過程中，以完全招募該研究。鑑於篩選期間使用的進行、處理和成像研究需要數週時間才能完成，我們預計最終受試者將在第三季度末完成篩選程序並接受第一劑多那奈單抗或安慰劑，該研究將完成 18 個月之後。鑑於註冊方面的這一進展，我們有信心達到適當描述多那奈單抗安全性特徵所需的藥物暴露數量和持續時間，從而允許在今年年底前提交監管報告。與 FDA 的討論與我們之前支持在 2021 年底之前提交的聲明一致。

I also want to provide a few comments on how we believe the national coverage determination opened for monoclonal antibody therapies targeting amyloid by the Centers for Medicare & Medicaid Services may impact Lilly and donanemab. We believe this NCD is a clear opportunity to focus treatment on the patients most likely to benefit from amyloid plaque-reducing therapies. This would align with our goals, which have long been to use advanced diagnostic tools to identify the right patients that can benefit the most from amyloid-reducing therapies.

我還想就我們如何認為醫療保險和醫療補助服務中心針對澱粉樣蛋白的單克隆抗體療法開放的全國覆蓋範圍確定可能會影響禮來和多那奈提供一些評論。我們相信，這種 NCD 是一個明顯的機會，可以將治療重點放在最有可能從減少澱粉樣斑塊治療中受益的患者身上。這與我們的目標一致，長期以來，我們的目標是使用先進的診斷工具來確定可以從減少澱粉樣蛋白治療中獲益最多的合適患者。

We're particularly encouraged that our progress with the plasma P-tau217 assay could open up broader access to diagnostic tools. Still, despite the advances in diagnostics and the promise of donanemab, we acknowledge the current skepticism in the national discussion. And we hope that each drug will be evaluated by payers and prescribers based on its own data. This could be particularly important, given the data I've shared today, which suggest that the degree of donanemab's amyloid plaque clearance relates to clinical benefit.

我們尤其感到鼓舞的是，我們在血漿 P-tau217 檢測方面的進展可以為診斷工具開闢更廣泛的途徑。儘管如此，儘管在診斷方面取得了進展，並且多納奈單抗前景廣闊，但我們承認目前在全國討論中的懷疑態度。我們希望每種藥物都將由付款人和開藥人根據自己的數據進行評估。鑑於我今天分享的數據，這可能特別重要，這表明多那奈瑪的澱粉樣蛋白斑塊清除程度與臨床益處有關。

In summary, we look forward to submitting donanemab to the FDA later this year with the potential to bring a robust amyloid plaque-clearing agent with limited treatment duration to market for early symptomatic Alzheimer's patients in 2022 with potential replicated clinical efficacy results expected in 2023.

總之，我們期待在今年晚些時候向 FDA 提交 donanemab，有可能在 2022 年為早期有症狀的阿爾茨海默病患者帶來一種治療時間有限的強大的澱粉樣斑塊清除劑，並有望在 2023 年獲得可複制的臨床療效結果。

Transitioning now to Verzenio. On the last earnings call, we commented that FDA had asked to see an overall survival trend in favor of Verzenio in the monarchE trial in adjuvant breast cancer. We also noted that the OS data set is quite immature in the overall population, which makes interpretation challenging. We have now provided to the FDA additional data from the monarchE study, and we were encouraged to see continued strengthening of the primary endpoint of invasive disease-free survival, IDFS, as well as consistent benefit in the key secondary endpoint of distant recurrence-free survival, DRFS. Of note, with this continued follow-up, we can now confirm this benefit extends beyond the 2-year Verzenio treatment period. We look forward to disclosing this new analysis at a medical meeting this fall.

現在過渡到 Verzenio。在上次財報電話會議上，我們評論說 FDA 已要求在 monarchE 輔助乳腺癌試驗中看到有利於 Verzenio 的總體生存趨勢。我們還注意到，OS 數據集在總體人群中相當不成熟，這使得解釋具有挑戰性。我們現在已經向 FDA 提供了來自 monarchE 研究的額外數據，我們很高興看到主要終點（無侵襲性疾病生存期 IDFS）的持續加強，以及在關鍵次要終點無遠處復發方面的持續獲益生存，DRFS。值得注意的是，通過這種持續的隨訪，我們現在可以確認這種益處超出了 2 年的 Verzenio 治療期。我們期待在今年秋天的醫學會議上披露這一新分析。

Our discussions with the FDA have focused on the prespecified subpopulation of patients with high Ki67 index, a marker of increased cell proliferation. These patients have more aggressive disease and higher risk of relapse and thus are more mature for overall survival analysis. This group, which makes up approximately half of the monarchE population, are demonstrating an overall survival trend that favors the treatment arm. And based on FDA feedback, we expect an initial approval in adjuvant breast cancer in this population before the end of the year, in line with the current review cycle.

我們與 FDA 的討論集中在預先指定的高 Ki67 指數患者亞群上，這是細胞增殖增加的標誌物。這些患者俱有更具侵襲性的疾病和更高的複發風險，因此在總體生存分析方面更加成熟。該組約佔 monarchE 人口的一半，顯示出有利於治療組的總體生存趨勢。根據 FDA 的反饋，我們預計在今年年底之前，該人群的輔助性乳腺癌將獲得初步批准，這與當前的審查週期一致。

Importantly, since the IDFS and DRFS hazard ratios favoring Verzenio are similar in patients with high and low Ki67 index, we expect that the OS trend first seen in the Ki67 high population will, in time, be replicated in the broader study population. We hope to expand the label to the entire enrolled population in the future once we see more overall survival events in the broader population. To date, regulators outside the U.S. have not raised the same questions on overall survival.

重要的是，由於有利於 Verzenio 的 IDFS 和 DRFS 風險比在 Ki67 指數高和低的患者中相似，我們預計在 Ki67 高人群中首次出現的 OS 趨勢將及時在更廣泛的研究人群中復制。一旦我們在更廣泛的人群中看到更多的總體生存事件，我們希望將來將標籤擴展到整個登記人群。迄今為止，美國以外的監管機構尚未就總體生存率提出相同的問題。

Finally, moving to Olumiant. We shared in July that the FDA will not meet the PDUFA action date for the supplemental new drug application for atopic dermatitis. This delay is related to the FDA's ongoing assessment of JAK inhibitors. Patient safety is critical to Lilly, and we continue to further evaluate baricitinib's safety profile with ongoing randomized and observational safety studies. We're confident that the efficacy and safety data for baricitinib support a favorable benefit-risk profile for the treatment of atopic dermatitis, and we look forward to continuing to work with the FDA during the remainder of the review process. We do not have additional information on timing or specific action date from the FDA. But we see potential for regulatory action for atopic dermatitis in the U.S. later this year. We're committed to bringing Olumiant to market in the U.S. to help meet the needs for people living with atopic dermatitis.

最後，轉移到 Oluminant。我們在 7 月份分享了 FDA 不會滿足 PDUFA 行動日期為特應性皮炎補充新藥申請。這種延遲與 FDA 對 JAK 抑製劑的持續評估有關。患者安全對禮來至關重要，我們繼續通過正在進行的隨機和觀察性安全性研究進一步評估巴瑞替尼的安全性。我們相信巴瑞克替尼的療效和安全性數據支持治療特應性皮炎的有利收益風險概況，我們期待在審查過程的剩餘時間繼續與 FDA 合作。我們沒有來自 FDA 的有關時間或具體行動日期的額外信息。但我們看到今年晚些時候在美國對特應性皮炎採取監管行動的潛力。我們致力於將 Olumiant 推向美國市場，以幫助滿足特應性皮炎患者的需求。

Slide 20 shows select pipeline opportunities as of July 30 and Slide 21 shows potential key events for the year. There have been several additional major developments since our last earnings call and I'll cover these by therapeutic area. In May, we shared the positive results for tirzepatide in SURPASS-4 and announced that the SURPASS program met regulatory submission requirements for evaluating cardiovascular risk and confirmed our intention to submit a registration package for tirzepatide in type 2 diabetes to global regulatory authorities by the end of 2021.

幻燈片 20 顯示了截至 7 月 30 日的選定管道機會，幻燈片 21 顯示了今年潛在的關鍵事件。自上次財報電話會議以來，還有一些其他重大進展，我將按治療領域介紹這些進展。 5 月，我們分享了 tirzepatide 在 SURPASS-4 中的積極結果，並宣布 SURPASS 項目符合評估心血管風險的監管提交要求，並確認我們打算在年底前向全球監管機構提交 tirzepatide 用於 2 型糖尿病的註冊包2021 年。

At ADA in June, tirzepatide was a large focus as we shared detailed data for the first 4 studies from the tirzepatide SURPASS program for the treatment of type 2 diabetes. These results support our belief that tirzepatide may represent a substantial improvement in the treatment of patients with type 2 diabetes with early and unsurpassed improvements in A1c and body weight reduction across doses. We remain on track for global regulatory submissions before the end of this year. We are also excited about tirzepatide's opportunity across multiple indications, including cardiovascular outcomes, obesity, NASH and heart failure. In Q2, we initiated SUMMIT, our planned Phase III study for tirzepatide in heart failure.

在 6 月的 ADA 上，tirzepatide 是一大焦點，因為我們分享了 tirzepatide SURPASS 計劃中用於治療 2 型糖尿病的前 4 項研究的詳細數據。這些結果支持我們的信念，即 tirzepatide 可能代表 2 型糖尿病患者治療的顯著改善，A1c 和跨劑量體重減輕的早期和無與倫比的改善。我們仍將在今年年底之前提交全球監管文件。我們也對 tirzepatide 在多種適應症方面的機會感到興奮，包括心血管結局、肥胖、 NASH 和心力衰竭。在第二季度，我們啟動了 SUMMIT，這是我們計劃的用於心力衰竭的替西帕肽 III 期研究。

In July, we achieved an important milestone with Jardiance as the first and only medicine to achieve a primary endpoint for heart failure with preserved ejection fraction, or HFpEF. The EMPEROR-Preserved Phase III trial met its primary endpoint and demonstrated significant risk reduction with Jardiance for the composite of cardiovascular death or hospitalization for heart failure in adults with HFpEF. This is a significant breakthrough for patients, and we're proud of what we've achieved here in partnership with Boehringer Ingelheim. We look forward to presenting detailed results from this study at the European Society of Cardiology on August 27, and we expect to submit this indication to regulators later this year.

7 月，我們實現了一個重要的里程碑，Jardiance 作為第一個也是唯一一個達到射血分數保留的心力衰竭（HFpEF）主要終點的藥物。 EMPEROR 保留的 III 期試驗達到了其主要終點，並證明 Jardiance 可顯著降低 HFpEF 成人心血管死亡或心力衰竭住院的複合風險。這對患者來說是一個重大突破，我們為與勃林格殷格翰合作所取得的成就感到自豪。我們期待於 8 月 27 日在歐洲心髒病學會上展示這項研究的詳細結果，我們預計將在今年晚些時候向監管機構提交這一適應症。

We also received approval in the EU for Jardiance HFrEF in June and expect regulatory action in the U.S. and Japan later this year for this indication. Additionally, we've advanced our GGG tri-agonist into Phase II for diabetes based on the promising data we shared at ADA, which supports the potential for differentiated efficacy from tirzepatide with respect to body weight while maintaining glycemic control. We also started 2 Phase I studies for diabetes and cardiovascular disease. Lastly, we removed one of our oral GIP/GLP Phase I molecules from our pipeline.

我們還在 6 月份獲得了歐盟對 Jardiance HFrEF 的批准，並預計今年晚些時候美國和日本將針對這一適應症採取監管行動。此外，基於我們在 ADA 分享的有希望的數據，我們已將 GGG 三激動劑推進到糖尿病的 II 期，這支持在保持血糖控制的同時，在體重方面與 tirzepatide 有差異化療效的潛力。我們還開始了 2 項針對糖尿病和心血管疾病的 I 期研究。最後，我們從管道中移除了一種口服 GIP/GLP I 期分子。

In oncology, we also continue to make important progress. Starting with Verzenio, we've initiated 2 Phase III studies since our last update. As planned, we've initiated an adjuvant study for HR+ HER2 breast cancer. And we are announcing today that a result -- as a result of a favorable blinded interim analysis for our Phase II trial in metastatic castration-resistant prostate cancer, we've also initiated the Phase III portion of this adaptive study. This action was based on a recommendation from the Independent Data Monitoring Committee, or IDMC.

在腫瘤學方面，我們也不斷取得重要進展。從 Verzenio 開始，自上次更新以來，我們已經啟動了 2 項 III 期研究。按照計劃，我們已經啟動了一項針對 HR+ HER2 乳腺癌的輔助研究。我們今天宣布了一個結果——由於我們對轉移性去勢抵抗性前列腺癌的 II 期試驗進行了有利的盲法中期分析，我們還啟動了這項適應性研究的 III 期部分。該行動基於獨立數據監測委員會 (IDMC) 的建議。

The IDMC reviewed interim efficacy and safety data and concluded that the results met the prespecified expansion criteria based on radiographic progression-free survival and recommended advancing the study to the registrational Phase III stage. While Lilly remains blinded to the study, we are obviously very pleased with this development and have already begun dosing patients in the Phase III portion of this trial. Given that the expansion of Phase III includes the cohort of patients who are in the Phase II study, these data remain blinded and we will not be disclosing these at medical meeting.

IDMC 審查了中期療效和安全性數據，並得出結論認為結果符合基於放射學無進展生存期的預先指定的擴展標準，並建議將研究推進到註冊 III 期階段。雖然禮來公司仍然對這項研究視而不見，但我們顯然對這一發展非常滿意，並且已經開始在該試驗的 III 期部分對患者進行給藥。鑑於 III 期的擴展包括 II 期研究中的患者隊列，這些數據仍然是盲目的，我們不會在醫學會議上披露這些數據。

On the development front in oncology, we also made progress with pirtobrutinib and our oral SERD. We've initiated the Phase III study for pirtobrutinib in relapsed/refractory MCL monotherapy, executing on our commitment to a robust Phase III program for this molecule. Regarding oral SERD, we announced our plans to begin a Phase III study later in 2021 based on the Phase I results we shared at ASCO in June that showed an efficacy and safety profile in line with our expectations. In addition, we've now achieved the first human dose for our next-generation KRAS G12C inhibitor. Lastly, in oncology, we announced that the FDA has accepted our submission of sintilimab for non-small cell lung cancer. This submission is an encouraging start for our collaborative efforts with Innovent to make sintilimab available in countries beyond China.

在腫瘤學的開發方面，我們在 pirtobrutinib 和我們的口服 SERD 方面也取得了進展。我們已經啟動了 pirtobrutinib 在復發/難治性 MCL 單藥治療中的 III 期研究，履行了我們對該分子的穩健 III 期計劃的承諾。關於口服 SERD，我們宣布計劃在 2021 年晚些時候開始一項 III 期研究，該研究基於我們 6 月份在 ASCO 上分享的 I 期結果，該結果顯示出符合我們預期的療效和安全性。此外，我們現在已經為我們的下一代 KRAS G12C 抑製劑實現了第一個人體劑量。最後，在腫瘤學方面，我們宣布 FDA 已接受我們提交的用於非小細胞肺癌的信迪單抗。本次提交是我們與信達（Innovent）合作在中國以外的國家提供信迪利單抗的一個令人鼓舞的開始。

In neurodegeneration, in addition to the donanemab news I just shared, we anticipate a Phase II readout for zagotenemab later this year and note that our GBA1 gene therapy asset from Prevail started a Phase II study in type 2 Gaucher disease. For immunology, we do not have additional significant updates in Q2, but we're looking forward to the Phase III readouts of lebrikizumab in atopic dermatitis and baricitinib for lupus later this year. We also submitted baricitinib for alopecia areata in Japan. Lastly, we're moving our COVID-19 antibody therapy, LY-CoV1404, now known as bebtelovimab, into Phase II to address viral variants as part of our ongoing commitment to help combat COVID-19, if needed.

在神經退行性病變方面，除了我剛剛分享的多納奈馬新聞外，我們預計今年晚些時候會公佈 zagotenemab 的 II 期讀數，並註意到我們來自 Prevail 的 GBA1 基因治療資產開始了針對 2 型戈謝病的 II 期研究。對於免疫學，我們在第二季度沒有額外的重大更新，但我們期待今年晚些時候對 lebrikizumab 治療特應性皮炎和 baricitinib 用於狼瘡的 III 期讀數。我們還在日本提交了用於治療斑禿的巴瑞替尼。最後，我們正在將我們的 COVID-19 抗體療法 LY-CoV1404（現在稱為 bebtelovimab）進入 II 期，以解決病毒變異問題，這是我們在必要時幫助對抗 COVID-19 的持續承諾的一部分。

To recap, Q2 was another positive quarter for R&D at Lilly, and we're excited about a number of further readouts and important milestones coming later this year, reflecting continued advances on behalf of patients suffering from disease. Now I'll turn the call back over to Dave for some closing remarks.

回顧一下，第二季度是禮來（Lilly）研發的又一個積極季度，我們對今年晚些時候將出現的一些進一步的讀數和重要的里程碑感到興奮，這反映了代表患有疾病的患者的持續進步。現在我將把電話轉回給戴夫做一些結束語。

Thanks a lot, Dan, appreciate that. Before we go to Q&A, let me sum up the progress we've made during this quarter. We've seen strength in our core business in the first half of this year and increased momentum in Q2. This is driven by strong volume-driven growth across key brands in most major geographies. We're pleased to see sequential top line growth this quarter as well as year-over-year margin expansion.

非常感謝，丹，很感激。在進行問答之前，讓我總結一下我們在本季度取得的進展。我們在今年上半年看到了我們核心業務的實力，並在第二季度增長了勢頭。這是由大多數主要地區的主要品牌的強勁銷量驅動增長所推動的。我們很高興看到本季度收入連續增長以及利潤率同比增長。

We made significant progress developing new medicines. And Q2 was another positive quarter for our pipeline as we announced plans to submit tirzepatide in type 2 diabetes and donanemab in Alzheimer's disease later this year as well as an approval for Jardiance in HFrEF, and as Dan outlined, positive results in HFpEF. We returned nearly $800 million to shareholders through dividends and completed $500 million in share repurchases, reflecting confidence in the ongoing strength of our business. As we look forward to the rest of the year, we are quite confident in our long-term prospects.

我們在開發新藥方面取得了重大進展。第二季度對我們的管道來說是另一個積極的季度，因為我們宣布計劃在今年晚些時候提交治療 2 型糖尿病的 tirzepatide 和治療阿爾茨海默病的 donanemab 以及批准用於 HFrEF 的 Jardiance，正如 Dan 概述的那樣，在 HFpEF 中取得了積極的結果。我們通過股息向股東返還了近 8 億美元，並完成了 5 億美元的股票回購，反映出對我們業務持續實力的信心。在展望今年餘下的時間時，我們對我們的長期前景充滿信心。

Before we move on to Q&A, I would like to share -- also like to share that we will hold a live investor meeting this December to highlight our R&D pipeline and progress for investors. We will also provide our initial 2022 guidance at this meeting. Given the limited physical space available, this event will have an accompanying webcast. We're hopeful that we can host this event in person but are watching the evolution of the pandemic closely, and we'll adjust accordingly to a virtual event, if needed. Our IR team will be in contact in the coming weeks to issue invitations and provide more logistical details on this meeting.

在我們繼續進行問答之前，我想分享一下——也想分享一下，我們將在今年 12 月舉行一次現場投資者會議，以突出我們的研發管道和投資者的進展。我們還將在本次會議上提供我們最初的 2022 年指導。鑑於可用的物理空間有限，本次活動將有一個附帶的網絡廣播。我們希望我們可以親自舉辦此活動，但正在密切關注大流行的演變，如果需要，我們將根據虛擬活動進行相應調整。我們的 IR 團隊將在未來幾週內與我們聯繫，以發出邀請並提供有關本次會議的更多後勤細節。

Now let me turn it over to Kevin to moderate our Q&A session.

現在讓我把它交給凱文來主持我們的問答環節。

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

謝謝，戴夫。 （操作員說明）Lois，您能否提供問答環節的說明？然後我們準備好迎接第一個來電者。

(Operator Instructions) And our first question is from the line of Terence Flynn from Goldman Sachs.

（操作員說明）我們的第一個問題來自高盛的 Terence Flynn。

Maybe, Dan, I was just wondering if you could elaborate at all on your comments regarding your discussions with the FDA on donanemab. It sounds like they're consistent with your expectations. But any more color you can provide if they've actually signed off fully on your plans to file the BLA? And then how much additional safety data would they want to see from the ongoing TRAILBLAZER-2 study?

也許，丹，我只是想知道您是否可以詳細說明您對與 FDA 討論多納奈馬的評論。聽起來它們與您的期望一致。但是，如果他們真的完全簽署了您提交 BLA 的計劃，您可以提供更多顏色嗎？然後他們希望從正在進行的 TRAILBLAZER-2 研究中看到多少額外的安全數據？

Thanks, Terence. Dan?

謝謝，特倫斯。擔？

Yes. Sure, Terence. Thanks for that question on donanemab and FDA and safety. In June, when we got the Breakthrough Therapy Designation and we announced our expectations to file the BLA by the end of the year, that was based on our current understanding of the situation. Since then, things have progressed, and I would say I'm even more confident now than I was then that we should have an adequate package to support a complete submission by the end of this year. That includes, of course, our confidence that we have enough safety data to support a full evaluation of the benefit/risk of this drug.

是的。當然，特倫斯。感謝您提出關於 donanemab 和 FDA 以及安全性的問題。 6 月，當我們獲得突破性治療指定並宣布我們希望在年底前提交 BLA 時，這是基於我們目前對情況的理解。從那以後，事情有了進展，我想說我現在比那時更有信心，我們應該有一個足夠的包來支持在今年年底之前完成提交。當然，這包括我們相信我們有足夠的安全數據來支持對該藥物的益處/風險進行全面評估。

I think given limited duration of dosing, that helps as well as given the near completion now of enrollment in TRAILBLAZER-2. So it's our intent then to use combined safety data from the completed Phase I and Phase II studies as well as an early look at safety data from that ongoing Phase III study to support the package. Now of course, with any ongoing study, there's always risk. We don't know what that safety data is going to show. If it's consistent with safety data we've collected prior to the study, then I think we should also be confident that, that would support a positive benefit/risk assessment and put us on track to launch next year as we said.

我認為鑑於給藥持續時間有限，這有助於以及考慮到現在即將完成 TRAILBLAZER-2 的註冊。因此，我們的意圖是使用已完成的 I 期和 II 期研究的綜合安全性數據，以及對正在進行的 III 期研究的安全性數據的早期研究，以支持該方案。當然，現在任何正在進行的研究都存在風險。我們不知道安全數據會顯示什麼。如果它與我們在研究之前收集的安全數據一致，那麼我認為我們也應該相信，這將支持積極的收益/風險評估，並使我們如我們所說的那樣在明年推出。

And the next question is from Ronny Gal from Bernstein.

下一個問題來自 Bernstein 的 Ronny Gal。

Two, the first one, I'll stay with donanemab. You have kind of suggested in your comments there that there will be a good chance to use some of the biomarkers that you are developing in the early commercial use of donanemab. Can you talk a little bit about what markets do you expect you have proved by when? And how do you see the -- essentially, the entire patient passage through the use of donanemab going forward? And how does it differ from other amyloid beta?

二，第一個，我會留在多那麥。您在評論中有一種建議，即有很好的機會使用您在 donanemab 的早期商業用途中開發的一些生物標誌物。你能談談你希望什麼時候能證明你的市場嗎？您如何看待 - 從本質上講，整個患者通過使用 donanemab 向前發展？它與其他β澱粉樣蛋白有何不同？

And second, Basaglar seems to have a bit of a price drop this quarter. Can you discuss a little bit what you're seeing here? What are you expecting with the approval of the first interchangeable biosimilars? Any impact there? And as we go forward, how should we think about that franchise?

其次，Basaglar 本季度的價格似乎有所下降。你能談談你在這裡看到的東西嗎？您對首個可互換生物仿製藥的批准有何期待？那裡有影響嗎？在我們前進的過程中，我們應該如何看待這個特許經營權？

Thanks, Ronny. We'll go to Dan for the questions on donanemab and then Mike Mason for the questions on Basaglar.

謝謝，羅尼。我們將向 Dan 詢問有關 donanemab 的問題，然後向 Mike Mason 詢問有關 Basaglar 的問題。

Yes. Thanks, Ronny, for the question on biomarkers and their commercial use. Of course, this has been an area of great progress and great investment by Lilly. We continue to put a lot of emphasis here. I think objectively, you wouldn't have had the progress that we're seeing now in Alzheimer's disease had it not been for the ability to select patients for treatment and follow their response treatment with biomarkers. We don't see that as a research-only application. That should be available, those kinds of tools, to patients in the clinical -- who are being clinically treated for Alzheimer's disease in the future.

是的。謝謝，Ronny，關於生物標誌物及其商業用途的問題。當然，這是禮來公司取得巨大進步和投入巨資的一個領域。我們在這裡繼續強調。我客觀地認為，如果不是因為能夠選擇患者進行治療並用生物標誌物跟踪他們的反應治療，你就不會有我們現在在阿爾茨海默病方面看到的進展。我們不認為這是一個僅限研究的應用程序。這些工具應該可以提供給臨床患者——他們將來會接受阿爾茨海默病的臨床治療。

So the status of the tools right now is both of the PET agents, the tau PET imaging with Tauvid that we use and the amyloid PET imaging with Amyvid, those are both, of course, FDA-approved and availability is somewhat limited right now, particularly for Tauvid, but could quickly be scaled with the launch of donanemab in the future. The third agent, which is probably the one that will be the most accessible to patients is the phospho-tau217 assay. Just as we continue to work on that assay, we're more and more impressed with its performance, its ability to identify patients, and even as I've shown today, track their progression. So this could be an answer for patients in the near term. We'll work hard to make that available. The bar is often lower for in vitro diagnostics than in vivo diagnostics. And I think there's good potential there.

因此，目前這些工具的狀態是兩種 PET 試劑，我們使用的 Tauvid 的 tau PET 成像和 Amyvid 的澱粉樣蛋白 PET 成像，當然，這些都是 FDA 批准的，而且目前可用性有點有限，尤其是對於 Tauvid，但隨著未來 donanemab 的推出，可能會迅速擴大規模。第三種藥物，可能是患者最容易獲得的一種藥物是磷酸化 tau217 檢測。正如我們繼續研究該檢測方法一樣，我們對其性能、識別患者的能力，甚至正如我今天所展示的那樣，跟踪他們的進展越來越印象深刻。因此，這可能是短期內患者的答案。我們將努力實現這一目標。體外診斷的標准通常低於體內診斷。我認為那裡有很好的潛力。

You asked about the patient flow once all these things are approved and available and presumably that happens around the time that donanemab is launched, if not before. I think it would make sense and fit with medical practice if screening starts with some sort of simple cognitive exams by a physician to assess the patient's eligibility to early Alzheimer's, then they would move on to probably a blood-based test like phospho-tau217. If that's positive, that could either be a basis for treatment, depending on if data support that, or that could triage patients to PET scans for further evaluation.

一旦所有這些事情都獲得批准和可用，您就詢問了患者流程，並且大概發生在 donanemab 推出時，如果不是之前的話。我認為，如果篩查從醫生進行的某種簡單的認知檢查開始以評估患者是否有資格患上早期阿爾茨海默氏症，那麼他們將繼續進行可能的基於血液的測試，如 phospho-tau217，這將是有意義的並且符合醫療實踐。如果這是積極的，這可能是治療的基礎，這取決於數據是否支持這一點，或者可以將患者分類到 PET 掃描以進行進一步評估。

Thanks, Dan. Now to Mike for the questions around Basaglar Q2 performance and Semglee interchangeability.

謝謝，丹。現在向 Mike 詢問有關 Basaglar Q2 性能和 Semglee 可互換性的問題。

Yes. Thanks for the question on Basaglar. The performance that you're seeing in the second quarter of '21 has primarily been driven by pricing pressure and volume pressure in the Medicaid segment for Basaglar. Let me give you a little bit of color on how the Medicaid segment works. There's really two different types of states: those that have one, single, unified preferred drug list across managed Medicaid and fee-for-service; and then others that have two different kind of unique preferred drug list across fee-for-service and a different one for managed Medicaid.

是的。感謝您提出關於 Basaglar 的問題。您在 21 年第二季度看到的業績主要受到 Basaglar 醫療補助部門的定價壓力和數量壓力的推動。讓我給你一點關於醫療補助部分如何運作的顏色。實際上有兩種不同類型的州：那些在託管的 Medicaid 和按服務收費中擁有一個單一、統一的首選藥物清單的州；然後是其他有兩種不同類型的獨特首選藥物清單（按服務收費）和另一種用於託管醫療補助的藥物清單。

What we've seen with Basaglar is when states decide to transition from having two preferred drug lists to a unified preferred drug list, the economics for the state tends to favor the long-standing brands like Lantus. And so at that point, you see if we have one state for -- in a managed Medicaid, you'll see the transition back to Lantus. So that's what you've seen driving our Q2 performance. Also in the managed Medicaid space, we have seen some pricing pressure there from Semglee that has required us to put more rebates on the -- in order to preserve volume for that. Now let me turn to kind of -- well, first of all, before turning to Semglee, know that the trends for Basaglar are fully baked into our guidance for the remaining part of 2021.

我們在 Basaglar 中看到的是，當各州決定從擁有兩個首選藥物清單過渡到一個統一的首選藥物清單時，該州的經濟狀況往往有利於 Lantus 等長期品牌。所以到那時，你會看到我們是否有一個州——在託管的醫療補助計劃中，你會看到回到 Lantus 的過渡。這就是您所看到的推動我們第二季度業績的原因。同樣在託管的醫療補助領域，我們已經看到來自 Semglee 的一些定價壓力，這要求我們提供更多的回扣——以保持銷量。現在讓我談談 - 好吧，首先，在轉向 Semglee 之前，要知道 Basaglar 的趨勢已完全融入我們對 2021 年剩餘時間的指導。

Now let me turn to Semglee. First of all, understand that Semglee has gained interchangeability just with Lantus, not with Basaglar. So we don't anticipate any immediate impact on Basaglar. If you look at Semglee performance to date, they've captured about 2% share of market on the TRx and about 1% of new treatment starts. And the vast majority of that has come from Medicare Part A, which is hospitals, and the Medicaid segment. If you look at the price point for Semglee, it's currently at $99 per vial and about $150 for 5 pack of pens.

現在讓我談談 Semglee。首先，要了解 Semglee 只是與 Lantus 而不是 Basaglar 獲得了可互換性。因此，我們預計不會對 Basaglar 產生任何直接影響。如果你看一下 Semglee 迄今為止的表現，他們在 TRx 上佔據了大約 2% 的市場份額，並且開始了大約 1% 的新治療。其中絕大多數來自醫療保險 A 部分，即醫院和醫療補助部分。如果您查看 Semglee 的價格點，目前每瓶 99 美元，5 支鋼筆約 150 美元。

And with the move to interchangeability, we really support any actions that help patients with diabetes to have more affordable out-of-pocket experience, which is why anyone, regardless of insurance status, is eligible to buy their monthly prescription of Lilly insulin for $35 or less through our Insulin Value Program. The Insulin Value Program has helped lower the average out-of-pocket costs for a monthly prescription of Lilly insulin, which also requires -- or includes multiple vials or insulin pen packs to $28.05 in the face of raising health insurance deductibles. So it's great that people living with diabetes has access to many options to lower their out-of-pocket costs. Thanks for the question.

隨著轉向可互換性，我們真的支持任何幫助糖尿病患者獲得更實惠的自費體驗的行動，這就是為什麼任何人，無論保險狀況如何，都有資格以 35 美元的價格購買他們每月的禮來胰島素處方或更少通過我們的胰島素價值計劃。胰島素價值計劃幫助降低了 Lilly 胰島素每月處方的平均自付費用，面對提高健康保險免賠額，這還需要或包括多個小瓶或胰島素筆包至 28.05 美元。因此，糖尿病患者可以有很多選擇來降低他們的自付費用，這真是太好了。謝謝你的問題。

And the next question is from Tim Anderson from Wolfe Research.

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

A couple of questions. Just your general thoughts on subcu dosing with antibodies to plaque, does that offer meaningful differentiation? At a high level, the benefits would seem quite obvious to being able to dose a drug at home. But some argue that it falls outside of a Medicare Part B framework, so maybe docs would be more inclined to stick with an infusion.

幾個問題。只是您對使用針對斑塊的抗體進行亞劑量給藥的一般想法，這是否提供了有意義的差異化？在較高的水平上，能夠在家中服藥的好處似乎非常明顯。但有些人認為它不屬於醫療保險 B 部分的框架，所以醫生可能更傾向於堅持輸液。

And I believe you originally did not pursue subcu because you're worried you wouldn't get enough drug across the blood-brain barrier. Roche has shown us that they can achieve that. So can we expect Lilly might also pursue a subcu? And would this require a formal Phase III study looking at plaque reduction as a primary endpoint? And then last quick question, why wouldn't something like P-tau217 become a separate meaningful revenue stream in its own right for Lilly?

而且我相信您最初沒有追求 subcu 是因為您擔心無法通過血腦屏障獲得足夠的藥物。羅氏向我們展示了他們可以做到這一點。那麼，我們可以期待禮來也可能追求 subcu 嗎？這是否需要一項將斑塊減少作為主要終點的正式 III 期研究？最後一個快速的問題，為什麼像 P-tau217 這樣的東西不能成為禮來獨立的有意義的收入來源？

Thanks, Tim. We'll go to Dan for all those questions.

謝謝，蒂姆。所有這些問題我們都會去找丹。

Okay. Thanks. No, it's a good question and line of questions here on subcu dosing for anti-amyloid therapies. Probably two factors that we have taken into account in addition to the ones you mentioned. First and most important is efficacy for patients. And I think all of the data that we have so far suggest and support the notion that deep and rapid clearance is key here. And so if you're going to go to subcu dosing, it's important to make sure you do get enough drug in so that you can quickly get patients to clear. That's not going to always be possible with every drug. I think the second consideration with subcu dosing is the duration of therapy. So if it's a limited duration of therapy, the difference between IV and subcu, if it's once a month for 6 months, that's not a big difference between IV and subcu, whereas if it's for the rest of your life, maybe that is a bigger difference.

好的。謝謝。不，這是一個很好的問題和一系列關於抗澱粉樣蛋白治療的 subcu 劑量的問題。除了您提到的因素之外，我們可能還考慮了兩個因素。首先也是最重要的是對患者的療效。而且我認為我們迄今為止獲得的所有數據都表明並支持這樣一種觀點，即深度和快速清除是關鍵。因此，如果您要進行 subcu 給藥，重要的是要確保您確實獲得了足夠的藥物，以便您可以快速讓患者清除。對於每種藥物，這並不總是可能的。我認為 subcu 給藥的第二個考慮因素是治療的持續時間。因此，如果是有限的治療時間，IV和subcu之間的差異，如果是每個月一次，持續6個月，IV和subcu之間的區別不大，而如果是在你的餘生中，那可能會更大區別。

And finally, with respect to our plans for subcu, I do think it's an important option to offer patients, notwithstanding the previous comments, even for a limited duration therapy, some patients may prefer it, assuming you can get the same kind of efficacy. I think with donanemab, that's unlikely to be possible, and we're not pursuing it, given the doses we need and the formulation we have. However, we have a second-generation antibody here that we call N3pG4, which I think is quite likely to be viable in a subcutaneous presentation. And that is our focus of development around N3pG4. My expectation around that is that it should be able to show comparable amyloid plaque lowering with subcutaneous dosing as donanemab does with IV dosing. If so, given the similarities between the drugs, we would seek an accelerated approval pathway for that drug in the future as sort of a subcutaneous version of donanemab, although it is a new enemy.

最後，關於我們的 subcu 計劃，我確實認為這是為患者提供的一個重要選擇，儘管有先前的評論，即使對於有限持續時間的治療，一些患者可能更喜歡它，假設您可以獲得相同的療效。我認為使用 donanemab，這是不可能的，鑑於我們需要的劑量和我們擁有的配方，我們沒有追求它。然而，我們這裡有一種稱為 N3pG4 的第二代抗體，我認為它很可能在皮下呈現中是可行的。這就是我們圍繞 N3pG4 開發的重點。我對此的期望是，它應該能夠顯示出與皮下給藥相似的澱粉樣蛋白斑塊降低，就像多納奈單抗與 IV 給藥一樣。如果是這樣，考慮到藥物之間的相似性，我們將在未來尋求加速批准該藥物的途徑，作為一種皮下版本的多那單抗，儘管它是一個新的敵人。

Your second question was around the phospho-tau assay and whether that's a significant revenue stream. It's certainly conceivable and we haven't sort of thought through all of our commercial plans around that. But really for Lilly -- and it may be significant for some companies. I think for Lilly though, our focus is on removing barriers for treatment to patients. And so as we think about how we position diagnostics and therapeutics in the marketplace, our focus will be on really making sure that most patients as possible can get treated appropriately.

你的第二個問題是關於 phospho-tau 檢測以及這是否是一個重要的收入來源。這當然是可以想像的，我們還沒有考慮過我們所有的商業計劃。但對於禮來公司來說真的很重要——這對一些公司來說可能意義重大。不過，我認為對於禮來，我們的重點是消除患者治療的障礙。因此，當我們考慮如何在市場上定位診斷和治療時，我們的重點將是真正確保盡可能多的患者能夠得到適當的治療。

And maybe just a comment -- thanks, Dan, Tim, on the access and payment environment, I think our priority at Lilly is always going to be how to make it easier for patients to get to a therapy and then we solve for value on the back end. There are clearly benefits in the short-duration treatment, like Dan said, with donanemab in Part B, they're going to be watched closely by their physicians initially anyway. There are real and important side effects, which require imaging analysis for this class of drugs. And so it's an intensively managed disease.

也許只是一個評論——謝謝，丹，蒂姆，關於訪問和支付環境，我認為我們在禮來公司的首要任務始終是如何讓患者更容易接受治療，然後我們解決價值後端。短期治療顯然有好處，就像 Dan 說的那樣，在 B 部分中使用 donanemab，無論如何，他們最初都會受到醫生的密切關注。存在真實且重要的副作用，需要對此類藥物進行影像學分析。所以它是一種集中管理的疾病。

But through time, as we've seen with other classes, as comfort level will rise in primary care, in particular, in using therapeutic antibodies to treat Alzheimer's, a more convenient form available at our local pharmacy, perhaps for self-injection or injection by a caregiver would be preferred. So our plans line up with -- in pursuing both those channels, although in early days, probably the intensive nature of the treatment and specialist nature will favor the infusion. But we're committed to both, and we're solving for patient convenience at the end of the day.

但隨著時間的推移，正如我們在其他課程中看到的那樣，初級保健的舒適度將會提高，特別是在使用治療性抗體治療阿爾茨海默氏症方面，這是我們當地藥房提供的一種更方便的形式，可能用於自我注射或註射最好由看護人。因此，我們的計劃符合 - 在追求這兩個渠道的過程中，儘管在早期，治療的密集性質和專業性質可能有利於輸液。但我們致力於兩者，最終我們會為患者提供便利。

The next question is from Chris Schott from JPMorgan.

下一個問題來自摩根大通的 Chris Schott。

Just one on donanemab and then one on Verzenio. Just I guess, my bigger question on donanemab is how are you thinking about the role of Abeta antibodies maybe prior to definitive cognition data being available? So I guess, do you see cognition data significantly expanding the market opportunity for these products? Or do you anticipate we're going to see broad usage, even in the event, let's just say, the additional cognitive readouts you see on donanemab were less definitive than what we saw in the Phase II? I'm just trying to see, do you think the whole market at this point is just going to move to plaque regression or reduction or at least cognition is still very important, I think, in terms of the commercial opportunity?

只有一個在 donanemab 上，然後一個在 Verzenio 上。只是我想，我對多納奈馬的更大問題是，在獲得明確的認知數據之前，您如何看待 Abeta 抗體的作用？所以我想，你是否看到認知數據顯著擴大了這些產品的市場機會？或者你是否預計我們會看到廣泛的使用，即使在事件中，讓我們說，你在 donanemab 上看到的額外認知讀數不如我們在第二階段看到的那麼明確？我只是想看看，你認為此時整個市場是否會轉向斑塊回歸或減少，或者至少認知仍然非常重要，我認為，就商業機會而言？

My second question was on the Verzenio update. I just -- just a two-parter here. Just when do you think you'll have that incremental OS data for the other 50% of the population? And how hard is it to identify these higher-risk patients as we think about maybe the initial commercial opportunity in adjuvant?

我的第二個問題是關於 Verzenio 的更新。我只是 - 只是這裡的兩個人。您認為您何時才能獲得其他 50% 人口的增量操作系統數據？當我們考慮到輔助治療的最初商業機會時，識別這些高風險患者有多難？

Thanks, Chris. We'll go to Dan for donanemab and then Anne for the questions on Verzenio.

謝謝，克里斯。我們會去 Dan 詢問 donanemab，然後去 Anne 詢問有關 Verzenio 的問題。

Yes. So your question is -- maybe I'll break it in two parts. The first part is like how important is in the near term to have additional cognitive benefit data for amyloid plaque lowering drugs. And then in the longer term, what happens if the confirmatory studies give a negative surprise. So in the short term, I'd just clarify that we have compelling clinical efficacy data for donanemab. The only trial that's going to be successful, a positive Phase II study and its primary endpoint showing cognitive benefits for donanemab, that's different, unique and exciting, published in the New England Journal, that's exciting. And I think that will be helpful even before we have the confirmatory data, being in that unique position.

是的。所以你的問題是——也許我會把它分成兩部分。第一部分就像在短期內獲得額外的認知益處數據對於降低澱粉樣斑塊藥物的重要性。然後從長遠來看，如果驗證性研究給出負面驚喜會發生什麼。因此，在短期內，我只想澄清一下，我們擁有令人信服的多納奈單抗臨床療效數據。唯一會成功的試驗，一項積極的 II 期研究，其主要終點顯示多那奈單抗的認知益處，這是不同的、獨特的和令人興奮的，發表在《新英格蘭雜誌》上，令人興奮。而且我認為，即使在我們擁有確認數據之前，處於那個獨特的位置，這也會有所幫助。

There will be some physicians, I'm sure, as are today, who still say, "I don't want to use a drug until I have cognitive data." Fine. For those physicians who are willing to make that link between the surrogate efficacy data and the Phase II data in donanemab, if you believe that lowering amyloid plaque is a good thing to do, you're going to want the drug that lowers amyloid plaque the most. And I think that's an exciting aspect of donanemab as well. But then we come to the confirmatory studies. I think surely everyone have to acknowledge, if for multiple sponsors, multiple drugs are all clearly negative, that would be a bad thing and we would retreat and say that this was a wrong way of thinking.

我敢肯定，會有一些醫生，就像今天一樣，他們仍然會說，“在我獲得認知數據之前，我不想使用藥物。”美好的。對於那些願意在替代療效數據和多那奈單抗 II 期數據之間建立聯繫的醫生，如果您認為降低澱粉樣蛋白斑塊是一件好事，那麼您將需要降低澱粉樣蛋白斑塊的藥物最多。我認為這也是 donanemab 令人興奮的一個方面。但隨後我們進行了驗證性研究。我想每個人肯定都必須承認，如果對於多個贊助商來說，多種藥物都明顯呈陰性，那將是一件壞事，我們會退縮並說這是一種錯誤的思維方式。

I think that scenario is extremely unlikely. I think the most likely scenario is probably a mixed picture. Some drugs will be better than others. Some trials will reach significance, others might not. You've heard me speak about the confidence in our trial, but we have to see the data. I think in that scenario, that will strengthen -- that would be good enough to reinforce the notion that amyloid is an important surrogate and reducing amyloid is a good idea.

我認為這種情況極不可能發生。我認為最有可能的情況可能是喜憂參半。有些藥物會比其他藥物更好。有些試驗會達到意義，有些則可能不會。你聽過我談論我們對試驗的信心，但我們必須看到數據。我認為在這種情況下，這將加強——這足以強化澱粉樣蛋白是一種重要的替代物並且減少澱粉樣蛋白是一個好主意的觀念。

Thanks, Dan. Anne, on Verzenio?

謝謝，丹。安妮，在 Verzenio 上？

Yes. Chris, thanks for the question. And as Dan shared, we are incredibly pleased with what we're seeing out of Verzenio and the monarchE data. And as he shared key endpoints, such as IDFS, have continued to strengthen with further follow-up. And now we have 2 years of median follow-up. And so very pleased with that. And as he shared, we remain very confident there will be an OS trend favoring Verzenio in the broader population. So we would work with the FDA to expand our label to include these patients in the future.

是的。克里斯，謝謝你的問題。正如 Dan 所分享的，我們對從 Verzenio 和 monarchE 數據中看到的結果非常滿意。隨著他共享關鍵端點（例如 IDFS），隨著進一步的跟進，它繼續得到加強。現在我們有 2 年的中位隨訪時間。對此非常滿意。正如他所分享的，我們仍然非常有信心在更廣泛的人群中出現有利於 Verzenio 的操作系統趨勢。因此，我們將與 FDA 合作，在未來擴大我們的標籤以包括這些患者。

So obviously, this is event-driven and so the timing of this will be determined by the event rate. So our next planned analysis is in the second half of '22. And this analysis will help us really further inform the timing of that final analysis. So as you commented, the overall survival data in the broader population is still immature. We still have less than 50% of the events needed to do that final OS analysis. But with what we're seeing, and again strong performance in both the high and low Ki67, we remain confident to see this trend in OS favoring Verzenio to replicate.

很明顯，這是事件驅動的，所以它的時間將由事件率決定。所以我們的下一個計劃分析是在 22 年下半年。這一分析將幫助我們進一步了解最終分析的時間安排。因此，正如您所評論的，更廣泛人群的總體生存數據仍然不成熟。我們仍然只有不到 50% 的事件需要進行最終的操作系統分析。但是，鑑於我們所看到的，以及在高 Ki67 和低 Ki67 中的再次強勁表現，我們仍然有信心看到 OS 有利於 Verzenio 複製的這種趨勢。

As far as Ki67, good news here is that this is really a familiar concept to physicians. It is already accepted as a prognostic factor in breast cancer. And it's really easily performed through an IHC assay, so very simple assay. And these are broadly available in the pathology labs. And the assay and the methodology that we used on monarchE is straightforward and proven to be accurate and really highly reproducible. So our belief is that oncologists will move to quickly adopt this in practice. And really, this clarity in patients with the highest risk, I think, will help to accelerate uptake in this setting. So we look forward to launching in this setting.

就 Ki67 而言，好消息是這對醫生來說確實是一個熟悉的概念。它已經被認為是乳腺癌的預後因素。而且它真的很容易通過 IHC 檢測進行，非常簡單的檢測。這些在病理學實驗室中廣泛可用。我們在 monarchE 上使用的分析和方法很簡單，並且被證明是準確的，並且具有高度可重複性。因此，我們相信腫瘤學家將迅速在實踐中採用這種方法。實際上，我認為，這種對風險最高的患者的明確性將有助於加速在這種情況下的吸收。所以我們期待在這個環境中推出。

The next caller is Umer Raffatt from Evercore.

下一位來電者是來自 Evercore 的 Umer Raffatt。

I surprisingly also want to talk about Alzheimer's today. Dan, I have three subparts. First, are you expecting to use interim data from your ongoing Phase III as part of the regulatory filing or during the review? Secondly, once the plaque is cleared, and I think 60% of patients have clearance by 12 months, what rate of onset of new amyloid plaque do you expect subsequently? And I'm just trying to understand your expectation on finite duration of dosing versus Biogen's opinion on continued dosing.

令人驚訝的是，我今天還想談談阿爾茨海默氏症。丹，我有三個子部分。首先，您是否希望將正在進行的第三階段的臨時數據作為監管備案的一部分或在審查期間使用？其次，一旦斑塊被清除，我認為 60% 的患者在 12 個月內清除，您預計隨後新的澱粉樣斑塊的發病率是多少？我只是想了解您對有限給藥持續時間的期望與百健（Biogen）對持續給藥的看法。

And then finally, I'm also trying to reconcile the slide you showed on the nonlinear model, the Conrado model, suggesting a relationship between plaque decrease and a slowing in clinical progression. Are you saying there's a relationship? Or are you saying there's a causality? Because you might recall the New England Journal paper on your Phase II mentioned there was no association between plaque and clinical benefit at patient level 1, Biogen's data suggested similar.

最後，我還試圖協調您在非線性模型康拉多模型上展示的幻燈片，表明斑塊減少與臨床進展減緩之間存在關係。你說有關係嗎？還是說有因果關係？因為您可能還記得《新英格蘭雜誌》關於您的 II 期論文提到，斑塊與患者 1 級的臨床益處之間沒有關聯，百健（Biogen）的數據表明類似。

Thanks, Umer. Dan?

謝謝，烏默爾。擔？

Okay. Three great questions, Umer. Thanks. So the first question, you asked if we use interim data. I commented that we'll take a safety cut of data in the right way to support that submission. We don't plan to support that submission nor do we see the need to support that submission with any looks at efficacy data. We have adequate efficacy data supporting the plaque lowering, which would be the basis of submission and approval under accelerated approval.

好的。三個好問題，烏默。謝謝。所以第一個問題，你問我們是否使用臨時數據。我評論說，我們將以正確的方式安全地削減數據以支持該提交。我們不打算支持該提交，我們也不認為有必要通過任何查看功效數據來支持該提交。我們有足夠的療效數據支持降低斑塊，這將是加速批准下提交和批准的基礎。

Your second question is once the plaque clears, how long does it take to come back? We have some data on that, that was also presented at AAIC. I didn't highlight it this morning. But what we found is that off-therapy, there is very slow, negligible really, regrowth of plaque. I think if you sort of extrapolate it out, it might take 14 or 15 years or something like that to regrow amyloid plaque. Average age of patients in this trial is 75. And remember, we haven't fully halted progression of disease. So that doesn't feel like a near-term thinking on redosing will be necessary to keep them clear. But we'll have the ability to follow up patients for many, many years and confirm that.

您的第二個問題是，一旦斑塊清除，需要多長時間才能回來？我們有一些關於這方面的數據，這些數據也在 AAIC 上提供。今天早上我沒有強調它。但我們發現，治療結束後，斑塊的再生非常緩慢，實際上可以忽略不計。我認為，如果您將其推斷出來，重新長出澱粉樣斑塊可能需要 14 或 15 年或類似的時間。該試驗中患者的平均年齡為 75 歲。請記住，我們還沒有完全阻止疾病的進展。因此，這並不意味著有必要在短期內考慮重做以保持清晰。但我們將有能力對患者進行多年隨訪並確認這一點。

Finally, I think you've correctly summarized the situation, which is that in our initial analysis, we didn't see a correlation and now we are reporting that we do see a correlation. Why is that? And of course, correlation can't prove causation, so it is just a correlation. So why do we see it now? I think what we learned was quite interesting. And that's that the amount of plaque you remove depends a lot on how much plaque you have to start with. So if you only have 50 centiloids of plaque, there's only so much you can remove. If you have 100 centiloids of plaque to base on, you can remove a lot more.

最後，我認為您已經正確地總結了這種情況，即在我們最初的分析中，我們沒有看到相關性，現在我們報告說我們確實看到了相關性。這是為什麼？當然，相關性並不能證明因果關係，所以它只是一種相關性。那麼為什麼我們現在看到它呢？我認為我們學到的東西很有趣。那就是您去除的牙菌斑量很大程度上取決於您必須開始使用多少牙菌斑。因此，如果您只有 50 centiloids 的牙菌斑，那麼您只能去除這麼多。如果你有 100 centiloids 的牙菌斑作為基礎，你可以去除更多。

So that turns out to be a pretty important confound in these kinds of correlations. The people who are -- have the more severe disease, perhaps longer duration, lower cognitive performance, older age, they might have more plaque at baseline, you can remove more, but they still might be the worst progressors than people who have lower plaque and you remove less. So I think our thinking initially and maybe the field thinking was a little bit backwards on this to look for a straight correlation between change and change without adjusting for all of those important baseline covariates.

因此，在這些相關性中，這被證明是一個非常重要的混淆。那些患有更嚴重疾病、可能持續時間更長、認知能力較低、年齡較大的人，他們可能在基線時有更多的斑塊，你可以去除更多，但與斑塊較低的人相比，他們仍然可能是最差的進展者你刪除的更少。所以我認為我們最初的想法，也許是現場的想法有點倒退，以尋找變化和變化之間的直接相關性，而不需要調整所有這些重要的基線協變量。

And our next question is from the line of Andrew Baum.

我們的下一個問題來自 Andrew Baum。

A couple of questions, please. Just going back to interim analysis for TRAILBLAZER-ALZ to not so much as used to support accelerated but to accelerate the readout for the full standard regulatory review, you're using a Bayesian disease progression model. Given that you're getting such a rapid clearance of Alzheimer's and that's linked to cognition in those patients who have that, do we have to assume that the follow-up is going to go out to the full 72 weeks? Or is there a possibility of early unblinding driven by efficacy in these patients? And then second, perhaps you could comment on the manufacturing capacity for donanemab as well as the regulatory outlook for your P-tau assay, assuming that you attain regulatory approval on the accelerators.

有幾個問題，請。回到 TRAILBLAZER-ALZ 的中期分析，與其說是用於支持加速，不如說是為了加速完整標準監管審查的讀數，您使用的是貝葉斯疾病進展模型。鑑於阿爾茨海默病的清除速度如此之快，並且這與那些患有這種疾病的患者的認知有關，我們是否必須假設隨訪將持續到整整 72 週？或者是否有可能在這些患者的療效驅動下進行早期揭盲？其次，假設您獲得了加速器的監管批准，也許您可以評論 donanemab 的製造能力以及您的 P-tau 分析的監管前景。

Thanks, Andrew. Dan, we'll go to you for those questions.

謝謝，安德魯。丹，這些問題我們會去找你的。

Yes. So Andrew, you've asked a follow-up question here, an important one, on the potential, even in the face of an accelerated review -- for accelerated approval rather, for plaque lowering, whether we'd still be keen to get that kind of data a bit earlier by pulling forward an interim on TRAILBLAZER-2. We haven't ruled that out. We also don't have plans at this moment in time. I think we just need to see where we are and where the field is. But really, the -- maintaining a pristine Phase III trial would probably be a pretty high priority, particularly if accelerated approval gives the path for patients to have access to the medicine, then it becomes less urgent to get that data faster.

是的。所以安德魯，你在這裡問了一個後續問題，一個重要的問題，關於潛力，即使面對加速審查 - 為了加速批准而不是為了降低斑塊，我們是否仍然熱衷於獲得通過在 TRAILBLAZER-2 上提前發布臨時數據，可以更早地獲取此類數據。我們沒有排除這種可能性。我們目前也沒有計劃。我認為我們只需要看看我們在哪里以及該領域在哪裡。但實際上，維持原始的 III 期試驗可能是一個相當高的優先事項，特別是如果加速批准為患者提供了獲得藥物的途徑，那麼更快地獲得這些數據就變得不那麼緊迫了。

So that's our current thinking. We've been working hard to make sure we have manufacturing capacity. I feel good about where we are to support launch and growth of donanemab and hopefully someday enter N3pG4 even to follow that. With respect to the commercialization of a P-tau diagnostic, there are different paths forward for an in vitro diagnostic, including a lab-developed test, or LDT, which can be done in a centralized location, for example, under CLIA. And that's a pretty fast path and that's one of the options that we consider.

這就是我們目前的想法。我們一直在努力確保我們有製造能力。我對我們在哪裡支持 donanemab 的推出和發展感到滿意，並希望有一天能進入 N3pG4 甚至跟進。關於 P-tau 診斷的商業化，體外診斷有不同的前進路徑，包括實驗室開發的測試或 LDT，這可以在集中位置完成，例如在 CLIA 下。這是一條非常快的路徑，也是我們考慮的選項之一。

And the next question comes 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 do you think about a potential outcome for the national coverage determination of monoclonal antibodies to treat Alzheimer's disease? And then second question is how would you think about pricing donanemab if it is approved?

所以我問你的第一個問題是，你如何看待全國范圍內確定用於治療阿爾茨海默病的單克隆抗體的潛在結果？然後第二個問題是，如果 donanemab 獲得批准，你會如何看待它的定價？

Thanks, Louise. Dan?

謝謝，路易絲。擔？

Okay. Thanks. Two sort of commercially focused questions on donanemab. I mean, the first one on the national coverage decision -- determination, of course, that's important. When -- I think it was widely said that when the first approval came, it was quite broad an indication. And then subsequently, the FDA, working with the sponsor, focused the patient population. I think there could still be opportunity for further focusing here. And that's one direction the experts at CMS may take.

好的。謝謝。關於 donanemab 的兩種商業焦點問題。我的意思是，第一個關於國家覆蓋範圍的決定——當然，決心很重要。何時-- 我認為人們普遍認為，當第一次獲得批准時，這是一個相當廣泛的跡象。隨後，FDA 與申辦方合作，重點關注患者群體。我認為這裡仍有進一步關注的機會。這是 CMS 專家可能採取的一個方向。

In that case, it could be requiring patients to have evidence of Alzheimer's pathology in the form of amyloid plaques or even tau pathology. As I said before, I think that matches our goals and what we think is right. It will take some time for that to play out probably over the next 9 months or so and surely will be part of some of those discussions and share our data and thinking in the right way. And then on pricing, I think I simply say it's too early to comment on that, we have some time yet.

在這種情況下，可能需要患者以澱粉樣斑塊甚至 tau 病理學的形式證明阿爾茨海默病的病理。正如我之前所說，我認為這符合我們的目標和我們認為是正確的。這可能需要一些時間才能在接下來的 9 個月左右內發揮出來，並且肯定會成為其中一些討論的一部分，並以正確的方式分享我們的數據和思考。然後關於定價，我想我只是說現在評論還為時過早，我們還有一些時間。

The next caller is Geoff Meacham from Bank of America.

下一位來電者是美國銀行的 Geoff Meacham。

Dan, you're popular today, so I just have a couple more for you. On donanemab, is there a hurdle that the FDA has provided in terms of number of patients for safety, either for the filing or during the review? And then as the data from TRAILBLAZER matures, what is your estimate on what the duration of therapy benefit could ultimately be? And then real quick on tirzepatide, just wanted to know, as you guys complete the filing, at this point, what's the gating factor as you look at the different geographies and you prepare?

丹，你今天很受歡迎，所以我只為你準備了幾個。關於 donanemab，FDA 是否在患者數量方面為安全提供了障礙，無論是在申請中還是在審查期間？然後隨著 TRAILBLAZER 數據的成熟，您對最終治療獲益持續時間的估計是多少？然後快速了解 tirzepatide，只是想知道，當你們完成歸檔時，在這一點上，當您查看不同的地區並準備時，門控因素是什麼？

Thanks, Geoff, we'll go to Dan for the donanemab questions and then Mike Mason on tirzepatide.

謝謝，Geoff，我們會去找 Dan 詢問 donanemab 問題，然後去找 Mike Mason 討論 tirzepatide。

Yes. So with respect to the safety hurdle for donanemab or for any drug, really it's having adequate exposures and duration of exposures in a broad population to be able to fully assess the benefit risk of a given drug. Now that's not a number that depends on the particulars of the drug, the population, of course, that you hope to treat the duration of therapy, of course, but also the particulars around the safety data and the efficacy data that you collect. So it would be nice and easy, I think, for sponsors and the FDA if there was a particular line in the sand that could be drawn. But as I said, it needs to be tailored for each drug. Based on our current thinking and analysis and discussions, as I said, I think we'll be there comfortably at the end of this year.

是的。因此，關於多納奈馬或任何藥物的安全障礙，實際上它在廣泛的人群中具有足夠的暴露和暴露持續時間，以便能夠充分評估給定藥物的益處風險。現在，這不是一個取決於藥物細節的數字，當然，人群，當然，你希望治療的治療持續時間，還有關於你收集的安全數據和療效數據的細節。因此，我認為，如果在沙子上可以劃出一條特定的線，那麼對於贊助商和 FDA 來說，這將是一件好事和容易的事。但正如我所說，它需要為每種藥物量身定制。正如我所說，根據我們目前的思考、分析和討論，我認為我們將在今年年底輕鬆地到達那裡。

Your second question was about -- I think it was about the duration of benefit as the TRAILBLAZER data mature. I commented on the duration of plaque lowering, which appears to be sustained. But I think, Geoff, you're getting at the duration of the cognitive benefit. We see a slowing of decline on average between that patients are still declining. You could ask, "Are the lines coming together or going apart?" I think on some of the cuts of the initial data, there might have been a perception that the lines were not diverging at the later time points, I think, as I showed the additional statistical methods. And even as we look at the raw data, we're pretty comfortable here that we have lines that diverge over time. And therefore, I would expect that, that benefit of slowing would continue over time but too soon to have real data on that.

你的第二個問題是關於——我認為這是關於隨著 TRAILBLAZER 數據成熟的好處的持續時間。我評論了斑塊降低的持續時間，這似乎是持續的。但我認為，傑夫，你正在獲得認知益處的持續時間。我們看到平均下降速度放緩，患者仍在下降。你可以問，“線是匯合還是分開？”我認為，在初始數據的一些削減中，我認為，當我展示了其他統計方法時，可能會有一種感覺，即這些線在後來的時間點沒有發散。即使我們查看原始數據，我們也很滿意我們的線條會隨著時間的推移而發散。因此，我預計，隨著時間的推移，放緩的好處將繼續存在，但要獲得有關這方面的真實數據還為時過早。

Thanks, Dan. Mike, on tirzepatide?

謝謝，丹。邁克，服用替西帕肽？

Yes. Thanks for the question. Our Phase III SURPASS program for type 2 diabetes is done and completed. So the only gating factor here is how quickly we can summarize the data and submit to the regulators, which we plan to do by the end of the year to major global regulators.

是的。謝謝你的問題。我們針對 2 型糖尿病的 III 期 SURPASS 計劃已經完成並完成。因此，這裡唯一的控制因素是我們能夠以多快的速度匯總數據並提交給監管機構，我們計劃在今年年底前向全球主要監管機構這樣做。

And the next caller is Carter Gould from Barclays.

下一個來電者是來自巴克萊的卡特古爾德。

Maybe I guess I'll try to take another stab at the pricing question. I appreciate it's early, but it is sort of the elephant in the room. And just maybe if Dave and team could comment just on the appropriateness of the pricing benchmarks in the space already today in Alzheimer's as you think about it. And then obviously, 3Q has tripped you in the past around Trulicity dynamics. So just hoping if you could just offer a little bit more clarity there on as you think about pricing headwinds into 3Q specifically.

也許我想我會嘗試在定價問題上再試一次。我很感激現在還早，但它有點像房間裡的大象。如果戴夫和他的團隊可以評論一下今天已經在阿爾茨海默氏症領域中定價基準的適當性，正如你所想的那樣。然後很明顯，3Q 過去曾在 Trulicity 動態方面絆倒你。因此，在您考慮具體到第三季度的定價逆風時，希望您能提供更多的清晰度。

Thanks, Carter. So we'll go to Dave for the question on pricing for donanemab and then Mike on Trulicity pricing dynamic.

謝謝，卡特。因此，我們將向 Dave 詢問有關 donanemab 定價的問題，然後向 Mike 詢問有關 Trulicity 定價動態的問題。

Yes, appreciate the question and we totally get the curiosity. There's, as you understand, probably lot of limitations of what we would say at this stage. One of the reasons for the limitation is really the ultimate label we have and the value we can demonstrate to customers is a key input at Lilly for pricing. And we have, fortunately, the only study in the space that hit its prespecified endpoint for disease reduction or disease progression reduction. And those are key. As we demonstrated at AAIC, we continue to cut that data. I think there was an earlier question about how we might differentiate in the NCD process. But that's one of them as we have this completed study with exquisite biomarker profiles of the product and can continue to elucidate what donanemab does in the brains of Alzheimer's patients in ways that perhaps others could not. And those are inputs as well.

是的，感謝這個問題，我們完全得到了好奇心。如您所知，我們在這個階段要說的內容可能有很多限制。限制的原因之一實際上是我們擁有的最終標籤，我們可以向客戶展示的價值是禮來公司定價的關鍵輸入。幸運的是，我們擁有該領域唯一一項達到減少疾病或減少疾病進展的預定終點的研究。這些是關鍵。正如我們在 AAIC 上展示的那樣，我們繼續削減這些數據。我認為有一個較早的問題是關於我們如何在 NCD 過程中進行區分。但這就是其中之一，因為我們已經完成了這項包含產品精緻生物標誌物概況的研究，並且可以繼續以其他人可能無法做到的方式闡明 donanemab 在阿爾茨海默病患者大腦中的作用。這些也是輸入。

Finally, Lilly has been a leader in value-based concepts and really partnerships to make sure that the appropriate patients can easily access at low out-of-pocket cost our medicines. And we're applying that thinking to this problem as well in the U.S. as well as outside. Our goal isn't to just get an approval, but to make sure that all of the people, millions in the U.S. who could qualify for it could access it on day 1. So those are all inputs into that process. And without throwing out a number here, which wouldn't be appropriate until we get an approval, that's how we think about it. Hopefully, that gives you some color behind the scenes.

最後，禮來在基於價值的概念和真正的合作夥伴關係方面一直處於領先地位，以確保合適的患者能夠以較低的自付費用輕鬆獲得我們的藥物。我們正在將這種想法應用到這個問題上，以及在美國和國外。我們的目標不僅僅是獲得批准，而是確保美國所有有資格獲得批准的人，數以百萬計的人都可以在第一天訪問它。所以這些都是對該過程的投入。並且不在這裡拋出一個數字，這在我們獲得批准之前是不合適的，這就是我們的想法。希望這能給你一些幕後的色彩。

Thanks, Dave. And then to Mike on Trulicity for pricing dynamics, pricing trends.

謝謝，戴夫。然後向 Mike 介紹 Trulicity 的定價動態和定價趨勢。

Yes. Thanks for the question. Really nothing new to report on Trulicity pricing. At the beginning of the year, we gave guidance that when you take a look at the impact of increased rates and market, second mix and offset by lower utilization of 340B and modest list price increases, that for the year, we would see low single-digit price decline for Trulicity. That's what we're experiencing, so really nothing new to update at this point in the year.

是的。謝謝你的問題。關於 Trulicity 定價的報導確實沒有什麼新鮮事。今年年初，我們給出的指導是，當您查看價格和市場、二次混合以及被 340B 利用率降低和適度的標價上漲所抵消的影響時，我們將看到今年的低單價-Trulicity 的數字價格下跌。這就是我們正在經歷的，所以在今年的這個時候真的沒有什麼新東西可以更新。

Yes. Let me just add just more general comment on pricing movement through the year. And I know we've had numerous conversations on this. And it does -- there does tend to be some volatility throughout the year. We do tend to see, as patients flow through the health care system, more pronounced impact from the coverage gap in the second and third quarter of the year. So you see that dynamic throughout every -- really every year, as Mike said.

是的。讓我對全年的定價變動添加更多一般性評論。我知道我們已經就此進行了多次對話。確實如此——全年確實會有一些波動。我們確實傾向於看到，隨著患者流經醫療保健系統，今年第二季度和第三季度的覆蓋率差距會產生更明顯的影響。因此，正如邁克所說，您每年都會看到這種動態。

And we built those assumptions into our full year guidance in terms of pricing dynamics for the year. And obviously, as we have more color and insight, we'll provide that. But right now, as we look at the full year estimate for U.S. pricing dynamic, it's consistent with what we previously discussed in terms of overall erosion. You saw 3% for the first half of the year, which is what you should expect for the full year.

我們將這些假設納入我們全年定價動態方面的指導。顯然，隨著我們有更多的色彩和洞察力，我們會提供這些。但是現在，當我們查看美國定價動態的全年估計時，它與我們之前在整體侵蝕方面討論的一致。今年上半年你看到了 3%，這是你對全年的預期。

The next question is from Seamus Fernandez from Guggenheim.

下一個問題來自古根海姆的 Seamus Fernandez。

Great. So really wanted to kind of focus in on abemaciclib in prostate cancer and the update that was provided. I think in an abstract published at AACR, some of the details were provided with regard to the sort of threshold for moving forward as it relates to the hazard ratio. And it cites a hazard ratio of 0.64, 80% power, so with a p-value of 0.1 to, I think, continue advancing into the next stage of CYCLONE 2.

偉大的。所以真的很想把重點放在前列腺癌中的 abemaciclib 和所提供的更新上。我認為在 AACR 發表的摘要中，提供了一些關於前進閾值的詳細信息，因為它與風險比有關。它引用了 0.64 的風險比，80% 的功率，所以我認為 p 值為 0.1 以繼續推進 CYCLONE 2 的下一階段。

So just wanted to clarify if that information is consistent and a driving force for moving forward. That would seem like a robust piece of information to have as we head into that. And then incremental to that, just wanted to get a sense of the magnitude of the opportunity that Lilly believes this would represent for Verzenio going forward. And if there are, let's say, Rb, some retinoblastoma-related requirements for enrollment or any other biomarker requirements that could limit the size of the patient population.

所以只是想澄清這些信息是否一致，是否是前進的動力。當我們開始研究時，這似乎是一個強有力的信息。然後對此進行增量，只是想了解禮來公司認為這將代表 Verzenio 前進的機會的重要性。如果有，比如說，Rb，一些與視網膜母細胞瘤相關的入組要求或任何其他可能限制患者群體規模的生物標誌物要求。

And then just as a follow-up, in terms of the NCD determination, just wanted to clarify if the pricing of the initially priced product would have any impact on Lilly's ability to independently price its own product and if that's part of the reason why Lilly has argued for the products being treated independently as part of the NCD rather than as a class.

然後作為後續行動，就 NCD 的確定而言，只是想澄清最初定價產品的定價是否會對禮來公司獨立定價自己的產品的能力產生任何影響，以及這是否是禮來公司的部分原因主張將產品作為非傳染性疾病的一部分而不是一個類別來獨立對待。

Thanks, Seamus. We're going to toss it to Dan first to start on Verzenio and then Anne will follow to round that out and then we'll go back to Dan for the NCD question.

謝謝，西莫。我們將首先將其拋給 Dan 以開始 Verzenio，然後 Anne 將跟進以完善該問題，然後我們將回到 Dan 討論 NCD 問題。

Yes. You're asking, Seamus, very smartly about the criteria to expand the study from a Phase II study to a Phase III study. I don't think we want to get into the very precise details on what that was. But you're correct that it was a very robust threshold. So we're excited to see that happen.

是的。 Seamus，您非常聰明地詢問將研究從 II 期研究擴展到 III 期研究的標準。我認為我們不想深入了解那是什麼的非常精確的細節。但你是對的，這是一個非常強大的閾值。所以我們很高興看到這種情況發生。

We take Phase III starts very seriously at Lilly. We don't want Phase III failures. So when we have studies like this one in any therapeutic area, where we move from Phase II to Phase III without ever seeing the data, we set aggressive bars that data really have to match to move forward to Phase III. So you can expect that's what we did here. Anne, for more detail.

在禮來，我們非常重視第三階段的啟動。我們不希望第三階段失敗。因此，當我們在任何治療領域進行類似的研究時，我們從 II 期進入 III 期而從未看到數據，我們設置了數據確實必須匹配才能進入 III 期的激進標準。所以你可以期待這就是我們在這裡所做的。安妮，了解更多詳情。

Thanks, Dan. Anne, for more detail there and also the magnitude of the opportunity we see in prostate?

謝謝，丹。安妮，那裡的更多細節以及我們在前列腺中看到的機會的大小？

Yes. I mean, as Dan said, we were incredibly pleased with this outcome and the recommendation by the DMC, and we set a very aggressive threshold on this adaptive design and we're impressed that it met that threshold. And I think it just continues to be another example of how Verzenio differentiates from the competition. So the Phase III is open, it's already enrolling patients. We anticipate the results of the analysis in 2024.

是的。我的意思是，正如丹所說，我們對這一結果和 DMC 的推薦感到非常滿意，我們為這種自適應設計設定了一個非常激進的門檻，我們對它達到了這個門檻印象深刻。我認為這只是 Verzenio 如何與競爭對手區分開來的另一個例子。所以第三階段是開放的，它已經在招募患者了。我們預計 2024 年的分析結果。

On the question on market size, so CYCLONE 2 is -- it's a metastatic castrate-resistant prostate cancer trial that really targets patients who have not yet received prior novel hormonal agent, so in earlier settings. So our initial research shows that the addressable market could be in the range of 25% to 50% of metastatic CRPC. So it's depending really a bit on how the market evolves with the use of NHAs in that earlier setting. So in the U.S., for example, based on that, we currently estimate between 7,000 and 14,000 patients would match that inclusion criteria for CYCLONE 2.

關於市場規模的問題，所以 CYCLONE 2 是 - 這是一項轉移性去勢抵抗性前列腺癌試驗，真正針對尚未接受過先前新型激素藥物的患者，因此在早期環境中。所以我們的初步研究表明，潛在市場可能在轉移性 CRPC 的 25% 到 50% 之間。因此，這在一定程度上取決於市場在早期環境中如何隨著 NHA 的使用而演變。因此，例如在美國，基於此，我們目前估計有 7,000 至 14,000 名患者符合 CYCLONE 2 的納入標準。

And exciting in this space is that, along with being a high unmet need in a large patient population, there's also a long length of anticipated treatment duration. So this could be a treatment duration of up to 2 years or longer. So that's why we're particularly excited about this opportunity is what it delivers there. There is no Rb or other biomarker requirements in the study.

在這個領域令人興奮的是，除了在大量患者中存在高度未滿足的需求外，預期的治療持續時間也很長。因此，這可能是長達 2 年或更長的治療時間。所以這就是為什麼我們對這個機會特別興奮的原因就是它在那裡提供的東西。研究中沒有 Rb 或其他生物標誌物要求。

Thanks, Anne. Dan, on NCD?

謝謝，安妮。丹，關於非傳染性疾病？

Last question was on NCD and why did I say that we think we -- each drug should be evaluated on its own merits. Is that an allusion to pricing or something like that? No, my primary focus here is on the patient and the outcomes that a drug could deliver, which, even within the same class, could be different. Our theory, and I just presented data today to support that theory, is that the amount of amyloid you remove and how quickly you do that is important for predicting outcomes.

最後一個問題是關於 NCD 的，為什麼我說我們認為我們 - 每種藥物都應該根據其自身的優點進行評估。這是暗示定價還是類似的東西？不，我在這裡的主要關注點是患者和藥物可以提供的結果，即使在同一類別中，這些結果也可能不同。我們的理論，我今天剛剛提供了支持該理論的數據，即您去除的澱粉樣蛋白的數量以及您去除的速度對於預測結果很重要。

If that's the case, you can easily imagine different drugs, even with the same class having different benefits for patients. And some of those benefits may be above a threshold for coverage and others may not, that's conceivable. Not what I anticipate is the most likely scenario, but we want to be prepared for all scenarios here.

如果是這樣的話，你可以很容易地想像不同的藥物，即使是同一個類別的藥物對患者有不同的好處。其中一些福利可能高於承保範圍，而另一些可能不會，這是可以想像的。不是我預期的最有可能發生的情況，但我們希望為這裡的所有情況做好準備。

The next question is from Vamil Divan from Mizuho Securities.

下一個問題來自瑞穗證券的 Vamil Divan。

Thanks for all the updates on the pipeline. So maybe a couple sort of separate topics that have been covered more on the call. So for one, on lebrikizumab, clearly that one maybe gets underappreciated a little bit. We got Phase III data coming up. Can you maybe just set some expectations on what you're hoping to see? I know you have a dosing advantage potentially with that product. But obviously, dupi is a pretty formidable competitor there. So maybe if you can just sort of frame what you're hoping to see.

感謝管道上的所有更新。所以也許有幾個單獨的主題在電話會議上得到了更多的討論。因此，對於 lebrikizumab，很明顯，一個人可能被低估了一點。我們得到了第三階段的數據。你能不能對你希望看到的東西設定一些期望？我知道您使用該產品可能具有劑量優勢。但顯然，dupi 在那裡是一個非常強大的競爭對手。所以也許如果你能把你希望看到的東西框起來。

And then tirzepatide, just one quick follow-up. I know you mentioned you started, I think you said, the HFpEF study for that product. Are you looking at that for HFrEF as well? I guess I don't remember you mentioning that. And if not, I'm just curious why you wouldn't pursue that.

然後是替西帕肽，只是一個快速的跟進。我知道你提到你開始，我想你說過，該產品的 HFpEF 研究。您是否也在為 HFrEF 尋找它？我想我不記得你提到過。如果沒有，我只是好奇你為什麼不追求那個。

Thanks, Vamil. We'll go to Ilya for the question on lebrikizumab and then Mike for tirzepatide.

謝謝，瓦米爾。我們將向 Ilya 詢問有關 lebrikizumab 的問題，然後向 Mike 詢問 tirzepatide。

Great. Thank you for the question on lebrikizumab. We're excited to -- for the second half of the year to see the data related to our induction phase for lebrikizumab across a number of trials. And so what we're hoping to see and expect to see is replicating some of the positive signals we saw in Phase II, where we have strong efficacy in skin itch and we believe have a very good safety profile. And so we anticipate that lebrikizumab will have a very competitive profile versus DUPIXENT in a growing and a significant unmet need. And we see lebrikizumab being an important asset for us as we think about not only atopic dermatitis but our overall presence and strength in dermatology and our growing immunology franchise.

偉大的。感謝您提出關於 lebrikizumab 的問題。我們很高興在今年下半年看到與我們在多項試驗中的 lebrikizumab 誘導階段相關的數據。所以我們希望看到和期望看到的是複制我們在第二階段看到的一些積極信號，我們在皮膚瘙癢方面有很強的療效，我們相信有很好的安全性。因此，我們預計 lebrikizumab 與 DUPIXENT 相比，在不斷增長且未得到滿足的需求方面具有非常強的競爭力。我們認為 lebrikizumab 對我們來說是一項重要資產，因為我們不僅考慮特應性皮炎，還考慮我們在皮膚病學的整體存在和實力以及我們不斷增長的免疫學專營權。

Thanks, Ilya. Mike?

謝謝，伊利亞。麥克風？

Okay. Thanks for the question. Yes, we have only announced a HFpEF study for tirzepatide. And that's currently all we're planning on announcing at this point. I think we're very confident in the opportunity of tirzepatide in the HFpEF. When you look at patients that have HFpEF, there's a large segment that also are obese. And obesity is a distinct phenotype within this patient population. So I think we feel good about our -- the results we've seen in our Phase II studies that give us, I think, confidence that we'll be successful in HFpEF. And so right now, our efforts are focused on HFpEF.

好的。謝謝你的問題。是的，我們只宣布了一項針對 tirzepatide 的 HFpEF 研究。這就是我們目前計劃宣布的全部內容。我認為我們對 HFpEF 中 tirzepatide 的機會非常有信心。當您查看患有 HFpEF 的患者時，有很大一部分也是肥胖的。肥胖是該患者群體中的一種獨特表型。因此，我認為我們對我們在 II 期研究中看到的結果感覺良好，我認為這讓我們相信我們將在 HFpEF 中取得成功。所以現在，我們的工作重點是 HFpEF。

The next caller is Steve Scala from Cowen.

下一位來電者是來自 Cowen 的 Steve Scala。

Two questions. First, on the Q1 earnings call, Lilly said in monarchE, there had been 76 events, 39 on abemaciclib, 37 on control. Can you provide an update with numbers on a like-for-like basis? And then secondly, on your oral SERD, did Lilly see potential for differentiation in the ASCO data? And if so, what differentiation did it see, particularly as competitor data and news flow evolves? Lilly has previously said it would not pursue a me-too SERD. So I'm wondering what is different about yours.

兩個問題。首先，在第一季度財報電話會議上，禮來在 monarchE 中表示，有 76 個事件，39 個在 abemaciclib 上，37 個在 control 上。你能提供類似的數字更新嗎？其次，在您的口頭 SERD 中，禮來公司是否看到了 ASCO 數據的差異化潛力？如果是這樣，它看到了什麼差異化，特別是隨著競爭對手數據和新聞流的發展？ Lilly 此前曾表示，它不會追求我的 SERD。所以我想知道你的有什麼不同。

Thanks, Steve. We'll go to Anne for the first question on Verzenio and then Jake for the question on oral SERD differentiation.

謝謝，史蒂夫。我們將向 Anne 提出關於 Verzenio 的第一個問題，然後向 Jake 提出關於口腔 SERD 區分的問題。

Well, thanks, Steve. And as Dan shared, we're going to be presenting data from this recent analysis at a medical meeting later this year. So we won't be able to share further details and then obviously due to the embargo. But as you can tell, we are very pleased to see the data continue to strengthen in this latest analysis with more than 2 years of follow-up.

好吧，謝謝，史蒂夫。正如 Dan 所分享的，我們將在今年晚些時候的一次醫學會議上展示這項最近分析的數據。因此，由於禁運，我們將無法分享更多細節。但正如您所知，我們很高興看到這項最新分析中的數據繼續加強，並進行了 2 年多的跟踪。

As we stated previously, the overall survival data remains immature. So at this point, what I can share is we have less than half of the events needed, so less than 50% of the events needed for the prespecified OS analysis. So the data remains immature. Again, we were really pleased, even with that immaturity, to see that the patients with highest risk already had this favorable trend. But thanks for the question and look forward to sharing more at a meeting later on.

正如我們之前所說，總體生存數據仍然不成熟。所以在這一點上，我可以分享的是，我們需要的事件不到一半，因此預定義的操作系統分析所需的事件不到 50%。所以數據仍然不成熟。再一次，我們真的很高興，即使是不成熟的，看到風險最高的患者已經有了這種有利的趨勢。但感謝您提出問題，並期待稍後在會議上分享更多信息。

Thanks, Anne. Jake?

謝謝，安妮。傑克？

Sure, happy to take the question on SERD. We're pleased with how the drug is performing clinically. It's doing everything that we expected it to do from a pharmacology, safety and efficacy perspective. I think the data package that we presented at ASCO and that which we continue to see in the trial subsequent to ASCO placed the drug in a vacuum on par with the best agents in development from our peers. But this is not a class of medicine that stands on its own, period. This is really a development program. And I think as it relates to me-too-ism, what I would say is that we're not interested in pursuing a me-too development program, and we stand by that statement.

當然，很高興回答關於 SERD 的問題。我們對該藥物在臨床上的表現感到滿意。從藥理學、安全性和有效性的角度來看，它正在做我們期望它做的一切。我認為我們在 ASCO 上展示的數據包以及我們在 ASCO 之後的試驗中繼續看到的數據包使該藥物處於真空狀態，與我們同行開發的最佳藥物不相上下。但這不是一類獨立存在的藥物。這真的是一個開發計劃。而且我認為，由於它與我也是主義有關，我想說的是我們對追求我也是的發展計劃不感興趣，我們支持這一聲明。

And frankly, our leadership position in breast cancer, in particular with emerging Verzenio data as we've been talking about today, I think, put us in a unique position as it relates to this class of medicines. That all having been said, I also think we are a bit more cautious about the long-term role of SERDs in this landscape. And we're looking forward to some randomized data for the first time from some of our competitors later this year that I think will shed some light on where these drugs ought to fit in the overall treatment paradigm.

坦率地說，我們在乳腺癌方面的領導地位，特別是我們今天一直在談論的新興 Verzenio 數據，我認為，使我們處於與此類藥物相關的獨特位置。說了這麼多，我也認為我們對SERD在這個領域的長期作用更加謹慎。我們期待今年晚些時候我們的一些競爭對手首次提供一些隨機數據，我認為這些數據將闡明這些藥物應該適合整體治療範式的位置。

And that comes from Matthew Harrison from Morgan Stanley.

這來自摩根士丹利的馬修哈里森。

Great. I guess, two for me. So first, just a follow-up with two parts on the Conrado model. One, do we know regulator's view of this model? And then secondly, maybe if you can just explain what we're seeing in a little bit more detail. It looks like you're seeing about a 40% regression, slowing at 100% clearance. I assume this is over 18 months. Would you expect that to continue to compound? I'm just wondering why only sort of 40% slowing when you've cleared all the plaque. And then just a second follow-up on SERD, any plans to look at that in combination with CDK4/6 or other combinations?

偉大的。我想，兩個給我。因此，首先，只是對 Conrado 模型的兩個部分進行跟進。一、我們知道監管者對這種模式的看法嗎？其次，也許你能更詳細地解釋一下我們所看到的。看起來你看到了大約 40% 的回歸，在 100% 的清除速度下放慢了速度。我認為這是超過 18 個月。你會期望這種情況繼續惡化嗎？我只是想知道為什麼當你清除所有斑塊後速度只有 40%。然後只是對 SERD 的第二次跟進，是否有計劃將其與 CDK4/6 或其他組合結合使用？

Thanks, Matthew. We'll go to Dan for the questions on the Conrado model and then Jake on SERD.

謝謝，馬修。我們將向 Dan 詢問有關 Conrado 模型的問題，然後向 Jake 詢問有關 SERD 的問題。

Yes. Thanks, Matthew, for the question there. No, we don't have a regulator's view on the Conrado model. But we're encouraged that this model was built, as I said earlier, by the CAMD -- by data from the CAMD consortium and has been around for a while and used for various applications. What we're doing here though, to be clear, is checking a patient's progression against what we predict their progression would be, so knowing all of their baseline factors, how much would they predicted to have progressed had they not been on drug versus how much did they actually progress. And so that's essentially what you're seeing in the graph.

是的。謝謝，馬修，那裡的問題。不，我們沒有監管機構對 Conrado 模型的看法。但我們感到鼓舞的是，正如我之前所說，這個模型是由 CAMD 構建的——由來自 CAMD 聯盟的數據構建，並且已經存在了一段時間並用於各種應用程序。不過，要明確的是，我們在這裡所做的是檢查患者的進展與我們預測的進展情況，因此了解他們所有的基線因素，如果他們沒有服用藥物，他們預計會進展多少，而不是如何他們實際上進步了很多。所以這基本上就是你在圖表中看到的。

You're right, even with full plaque clearance, there's still some progression. There's only a 40% decrease. Now that's as big an effect as anyone ever has talked about in Alzheimer's disease. But surely, over time, we're going to need additional therapeutics for Alzheimer's beyond just clearing the plaque, at least in this stage of disease. And I think that's probably where tau therapeutics come into play. So that's how we think about it. I think earlier in the disease, of course, it could be quite different. Perhaps if you get it early enough, you could have 100% disease slowing of progression and in essence, no Alzheimer's. But that is yet to be proven.

你是對的，即使完全清除牙菌斑，仍有一些進展。僅減少了 40%。現在，這是任何人在阿爾茨海默病中談論過的一樣大的影響。但可以肯定的是，隨著時間的推移，我們將需要額外的治療阿爾茨海默病的方法，而不僅僅是清除斑塊，至少在這個疾病階段是這樣。我認為這可能就是 tau 療法發揮作用的地方。所以我們就是這麼想的。我認為在疾病的早期，當然，它可能完全不同。也許如果你足夠早地得到它，你可能會 100% 地減緩疾病的進展，從本質上講，沒有阿爾茨海默氏症。但這還有待證明。

Thanks, Dan. Going to Jake for that question on SERD.

謝謝，丹。在 SERD 上向 Jake 提問。

Yes, the question on SERD. Of course, we plan to explore combining our oral SERD with CDK4/6, in particular, with abemaciclib. We're doing that right now in the context of an expansion cohort of the Phase I/II trial. The same trial for which we presented data at ASCO has expansion cohorts that contemplate rational combinations, including with abemaciclib.

是的，關於SERD的問題。當然，我們計劃探索將我們的口服 SERD 與 CDK4/6 結合，特別是與 abemaciclib。我們現在正在 I/II 期試驗的擴展隊列的背景下這樣做。我們在 ASCO 提供數據的同一試驗具有考慮合理組合的擴展隊列，包括與 abemaciclib 的組合。

Thanks, Jake. And Matthew, thanks for your questions, and we've exhausted the queue. We'll go to Dave for the close.

謝謝，傑克。 Matthew，感謝您的提問，我們已經排滿了隊列。我們將去戴夫為結束。

Thanks, Kevin. Thanks to Dan for answering all those questions. We appreciate your participation in today's call and your interest in the company, of course. We continue to see growth with our broad commercial portfolio. And we have strong momentum across our core business, supported by a breadth of brands and accelerating classes and robust growth across U.S., Europe and China. In addition, as you heard today, we believe we have a compelling pipeline with industry-leading opportunities. And we remain focused on bringing new medicines to patients and creating value for all our stakeholders.

謝謝，凱文。感謝 Dan 回答了所有這些問題。當然，我們感謝您參加今天的電話會議以及您對公司的興趣。我們繼續通過我們廣泛的商業組合看到增長。在美國、歐洲和中國的廣泛品牌和加速課程以及強勁增長的支持下，我們的核心業務勢頭強勁。此外，正如您今天所聽到的，我們相信我們擁有引人入勝的管道和行業領先的機會。我們仍然專注於為患者帶來新藥，並為我們所有的利益相關者創造價值。

Thanks again for dialing in. Please follow up with Investor Relations team if you have any questions we have not addressed today, and hope you have a great day. Thanks.

再次感謝您撥入。如果您有任何我們今天未解決的問題，請與投資者關係團隊聯繫，並希望您度過愉快的一天。謝謝。

Thank you. And ladies and gentlemen, that does conclude our conference for today. Thank you for your participation and for using AT&T Teleconference Service. You may now disconnect.

謝謝你。女士們先生們，今天的會議到此結束。感謝您的參與和使用 AT&T 電話會議服務。您現在可以斷開連接。