禮來公司 (LLY) 2020 Q4 法說會逐字稿

Ladies and gentlemen, thank you for standing by, and welcome to the Lilly Q4 2020 Earnings Call.

女士們，先生們，感謝您的支持，歡迎參加禮來公司 2020 年第四季度財報電話會議。

(Operator Instructions) As a reminder, this conference is being recorded.

（操作員說明）作為提醒，本次會議正在錄製中。

I would now like to turn the conference over to our host, Vice President of Investor Relations, Mr. Kevin Hern.

我現在想將會議轉交給我們的東道主投資者關係副總裁 Kevin Hern 先生。

Please go ahead, sir.

請繼續，先生。

Good morning.

早上好。

Thank you for joining us for Eli Lilly and Company's Q4 2020 Earnings Call.

感謝您參加禮來公司 2020 年第四季度財報電話會議。

I'm Kevin Hern, Vice President of investor Relations.

我是投資者關係副總裁 Kevin Hern。

Joining me on today's call are Dave Ricks, Lilly's Chairman and CEO; Josh Smiley, Chief Financial Officer; Dr. Dan Skovronsky, Chief Scientific Officer; Anne White, President of Lilly Oncology; Ilya Yuffa, President of Lilly Biomedicines; and Mike Mason, President of Lilly Diabetes.

與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（Dave Ricks）；喬什·斯邁利，首席財務官； Dan Skovronsky 博士，首席科學官；禮來腫瘤學總裁 Anne White； Ilya Yuffa，禮來生物醫藥總裁；和禮來糖尿病公司總裁 Mike Mason。

We're also joined by Sara Smith and Lauren Zierke of the Investor Relations team.

投資者關係團隊的 Sara Smith 和 Lauren Zierke 也加入了我們的行列。

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

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。

Our actual results could differ materially due to a number of factors, including those listed on Slide 3. Information concerning factors that could cause actual results to differ materially is contained in our latest Form 10-K and subsequent Forms 10-Q and 8-K filed with the Securities and Exchange Commission.

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信息包含在我們最新的 10-K 表格和後續的 10-Q 和 8-K 表格中提交給美國證券交易委員會。

The information we provide about our products and pipeline is for the benefit of the investment community.

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。

It is not intended to be promotional and is not sufficient for prescribing decisions.

它不是為了促銷，也不足以做出處方決定。

As we transition to our prepared remarks, a reminder that our commentary will focus on non-GAAP financial measures, which exclude the financial contribution from Elanco during 2019, and present earnings per share as though the full disposition via the exchange offer was complete on January 1, 2019.

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，其中不包括 Elanco 在 2019 年的財務貢獻，並呈現每股收益，就好像通過交換要約完成的全部處置已於 1 月完成2019 年 1 月 1 日。

Now I'll turn the call over to Dave for a summary of our 2020 results.

現在，我將把電話轉給戴夫，以總結我們 2020 年的結果。

Thanks, Kevin.

謝謝，凱文。

On our guidance call in December 2019, we provided a framework for how we are thinking about the 2020 to 2025 period, noting our expectations to continue to deliver top-tier revenue growth and operating margin growing into the mid- to high 30s while continuing to increase R&D productivity.

在 2019 年 12 月的指導電話會議上，我們為我們如何考慮 2020 年至 2025 年期間提供了一個框架，並指出我們預計將繼續實現頂級收入增長和營業利潤率增長到 30 年代中期至高水平，同時繼續提高研發生產力。

As we met with investors throughout 2020, it was evident that while there was good insight into management's expectations for the next few years.

當我們在 2020 年全年與投資者會面時，很明顯，儘管管理層對未來幾年的預期有很好的洞察力。

Investors were increasingly focused on our ability to grow in the second half of this coming decade.

投資者越來越關注我們在未來十年後半段的增長能力。

In the past 2 months, we have begin -- we have begun to deliver answers to that question, with positive data for LOXO-305, tirzepatide and donanemab, each with a chance to significantly improve patient outcomes in areas of high unmet medical need.

在過去的 2 個月裡，我們已經開始——我們已經開始提供這個問題的答案，LOXO-305、tirzepatide 和 donanemab 的積極數據，每一個都有機會在高度未滿足的醫療需求領域顯著改善患者的治療效果。

We believe these are 3 of the most important and exciting pipeline assets in our industry and provide meaningful support for Lilly's growth potential beyond 2025.

我們相信這是我們行業中最重要和最令人興奮的 3 項管道資產，並為禮來公司 2025 年以後的增長潛力提供了有意義的支持。

Together with Verzenio data in early breast cancer last summer, we have significantly reinforced our growth prospects for the midterm and upgraded them for the long term.

與去年夏天早期乳腺癌的 Verzenio 數據一起，我們顯著加強了中期增長前景並對其進行了長期升級。

While these readouts drive incredible momentum for our future, I am also pleased with the way that we delivered in a complex and challenging 2020.

雖然這些讀數為我們的未來帶來了令人難以置信的動力，但我也對我們在復雜且充滿挑戰的 2020 年的交付方式感到滿意。

Our 2020 revenue enabled us to exceed our midterm revenue goal of 7% CAGR from the years 2015 to 2,020.

我們 2020 年的收入使我們能夠超過從 2015 年到 2,020 年 7% 的中期收入目標。

Turning to the quarter.

轉向季度。

Revenue grew an impressive 22% versus Q4 2019 or 20% in constant currency.

與 2019 年第四季度相比，收入增長了 22%，按固定匯率計算增長了 20%。

This strong performance was driven entirely by volume growth of 24 percentage points despite continued pricing headwinds and demand pressure from the effects of COVID-19.

儘管持續存在定價逆風和 COVID-19 影響帶來的需求壓力，但這一強勁表現完全是由 24 個百分點的銷量增長推動的。

Excluding bamlanivimab, revenue grew over 7% for the quarter.

不包括 bamlanimab，本季度收入增長超過 7%。

Key growth products continue to drive this volume and our revenue, now representing 55% of our base business.

主要增長產品繼續推動這一數量和我們的收入，現在占我們基礎業務的 55%。

We continued to advance our productivity agenda in Q4.

我們在第四季度繼續推進我們的生產力議程。

As the combination of strong revenue growth and modest operating expense growth drove significant margin expansion, our non-GAAP operating margin was approximately 33% with and without COVID-19 therapies, an improvement of roughly 650 basis points versus Q4 2019.

由於強勁的收入增長和適度的運營費用增長共同推動了利潤率的大幅增長，我們的非 GAAP 運營利潤率在使用和不使用 COVID-19 療法的情況下約為 33%，與 2019 年第四季度相比提高了約 650 個基點。

With continued margin expansion for the quarter and full year, excluding the impacts of COVID-19 on our business in 2020, we would have achieved our midterm operating margin as a percent of revenue goal of 31%.

隨著本季度和全年利潤率的持續增長，排除 COVID-19 對我們 2020 年業務的影響，我們將實現中期營業利潤率佔收入目標的 31%。

We're proud to have delivered nearly 1,000 basis points of operating margin expansion since 2016.

自 2016 年以來，我們很自豪地實現了近 1,000 個基點的營業利潤率擴張。

In addition to the strong business performance, we achieved multiple pipeline milestones since our Q3 earnings call.

除了強勁的業務表現外，自第三季度財報電話會議以來，我們還實現了多個管道里程碑。

These include: The positive results I noted for LOXO-305, tirzepatide and donanemab; the FDA granting emergency use authorizations for bamlanivimab and baricitinib to help patients with COVID-19; the submission of empagliflozin for heart failure in people with reduced injection fraction in the U.S., Europe and Japan, this is done in collaboration with Boehringer Ingelheim; and the submission of Verzenio in early breast cancer in the U.S.

其中包括： 我注意到 LOXO-305、tirzepatide 和 donanemab 的積極結果； FDA 授予 bamlanimab 和 baricitinib 緊急使用授權，以幫助 COVID-19 患者；與勃林格殷格翰合作，在美國、歐洲和日本提交了恩格列淨用於治療注射分數降低的人的心力衰竭；以及 Verzenio 在美國早期乳腺癌中的提交

During Q4, we put our growing operating cash flow to work, announcing a 15% increase in the dividend for the third consecutive year, as well as continuing to pursue external innovation to augment future growth prospects with the acquisition of Prevail Therapeutics.

在第四季度，我們將不斷增長的經營現金流投入使用，宣布股息連續第三年增長 15%，並通過收購 Prevail Therapeutics 繼續追求外部創新以擴大未來增長前景。

This acquisition adds a promising new modality for Lilly by creating a gene therapy program that will be anchored by Prevail's portfolio of clinical-stage and late-preclinical-stage gene therapies across Alzheimer's, Parkinson's, dementia, ALS and other neurodegenerative disorders.

此次收購通過創建一個基因治療計劃，為禮來（Lilly）增加了一種有前途的新模式，該計劃將以 Prevail 的阿爾茨海默氏症、帕金森氏症、癡呆症、ALS 和其他神經退行性疾病的臨床階段和晚期臨床前階段基因治療組合為基礎。

Moving to Slides 5 and 6, you'll see a list of key events since our last earnings call.

轉到幻燈片 5 和 6，您將看到自我們上次財報電話會議以來的關鍵事件列表。

In November, we announced that Aarti Shah, our Senior Vice President and Chief Information and Digital Officer, will retire in the first half of this year after 27 years of service to Lilly.

11 月，我們宣布我們的高級副總裁兼首席信息和數字官 Aarti Shah 在為禮來公司服務 27 年後將於今年上半年退休。

She's been an invaluable member of our Executive Committee and a leader who really models our values.

她一直是我們執行委員會的寶貴成員，也是真正樹立我們價值觀的領導者。

In addition to leading the development of our digital information strategy, she has developed and mentored talent throughout the organization and demonstrated a deep care for the patients we aim to serve.

除了領導我們數字信息戰略的發展，她還在整個組織內培養和指導人才，並對我們旨在服務的患者表現出深切的關懷。

I want to thank Aarti for her many contributions to Lilly.

我要感謝 Aarti 對 Lilly 的許多貢獻。

And now I'll turn the call over to Josh to review our Q4 and full year results.

現在，我將把電話轉給 Josh，以審查我們的第四季度和全年業績。

Thanks, Dave, and good morning.

謝謝，戴夫，早上好。

Slide 7 summarizes our non-GAAP financial performance in Q4 and 2020.

幻燈片 7 總結了我們在第四季度和 2020 年的非公認會計原則財務業績。

As Dave mentioned, revenue increased 22% this quarter compared to Q4 2019 and increased 7%, excluding bamlanivimab sales.

正如 Dave 所說，本季度的收入與 2019 年第四季度相比增長了 22%，增長了 7%，不包括 bamlanivimab 的銷售額。

Gross margin as a percent of revenue declined 130 basis points to 78.6%.

毛利率佔收入的百分比下降 130 個基點至 78.6%。

Excluding the impact of bamlanivimab revenue and the related manufacturing costs, gross margin as a percent of revenue was 79.9%, in line with Q4 2019 performance.

排除 bamlanivimab 收入和相關製造成本的影響，毛利率佔收入的百分比為 79.9%，與 2019 年第四季度的業績一致。

Moving down the P&L.

向下移動損益表。

Operating expenses grew 3% compared to the same quarter last year.

與去年同期相比，運營費用增長了 3%。

Marketing, selling and administrative expenses were down 8% as reduced activity due to COVID-19 and productivity measures offset investments in key growth products.

由於 COVID-19 和生產力措施導致活動減少，抵消了對關鍵增長產品的投資，營銷、銷售和管理費用下降了 8%。

R&D expenses increased 16% driven by investment in COVID-19 therapies.

由於對 COVID-19 療法的投資，研發費用增加了 16%。

Net of COVID-19 expenses, baseline R&D was relatively flat, and total operating expenses decreased over 5% compared to Q4 2019.

扣除 COVID-19 費用後，基線研發相對持平，與 2019 年第四季度相比，總運營費用下降了 5% 以上。

Operating income increased 53% compared to Q4 2019 as revenue growth far outpaced expense growth, resulting in operating income as a percent of revenue of 33% for the quarter.

與 2019 年第四季度相比，營業收入增長了 53%，因為收入增長遠遠超過支出增長，導致本季度營業收入佔收入的百分比為 33%。

Excluding the impact of COVID-19 therapies, operating income grew 34% in the quarter, and the operating margin for our base business was 32.7% for Q4.

排除 COVID-19 療法的影響，本季度營業收入增長 34%，第四季度基礎業務的營業利潤率為 32.7%。

Other income and expense was income of $477 million this quarter compared to income of $206 million in Q4 2019 driven by investment gains on public equities.

其他收入和支出是本季度的收入為 4.77 億美元，而 2019 年第四季度的收入為 2.06 億美元，主要受公共股票投資收益的推動。

As we noted in our Q3 earnings call, beginning in 2021, we will exclude the gains or losses due to equity investments from our non-GAAP measures.

正如我們在第三季度財報電話會議中指出的那樣，從 2021 年開始，我們將從我們的非公認會計原則指標中排除股權投資產生的收益或損失。

We have posted a supplemental investor workbook for Q4 on that basis to enable you to have an apples-to-apples comparison as we move into 2021 and compare to 2020 non-GAAP performance.

我們在此基礎上發布了第四季度的補充投資者工作手冊，以便您在進入 2021 年並與 2020 年非 GAAP 業績進行比較時進行比較。

Our tax rate was 14.4%, an increase of 180 basis points compared with the same quarter last year, driven primarily by net discrete tax items in both quarters.

我們的稅率為 14.4%，與去年同期相比增加了 180 個基點，主要是由於兩個季度的淨離散稅項。

At the bottom line, net income increased 58% while earnings per share increased 59%.

歸根結底，淨收入增長了 58%，而每股收益增長了 59%。

Net of COVID-19 therapies, net income and earnings per share increased 43%.

扣除 COVID-19 療法後，淨收入和每股收益增長了 43%。

Moving to Slide 8. You can see these same non-GAAP measures for the full year.

轉到幻燈片 8。您可以在全年看到這些相同的非 GAAP 指標。

In spite of the ongoing demand impact from the pandemic, we grew the top line at 10% or 6% excluding bamlanivimab.

儘管大流行對需求的持續影響，我們的收入增長了 10% 或 6%，不包括 bamlanivimab。

Excluding COVID-19 therapies, our operating margin expanded by 300 basis points contributing to 30% EPS growth while continuing to invest behind our newer products and pipeline.

不包括 COVID-19 療法，我們的營業利潤率擴大了 300 個基點，促成了 30% 的每股收益增長，同時繼續投資於我們的新產品和管道。

On Slide 9, we quantify the effect of price, rate and volume on revenue growth.

在幻燈片 9 中，我們量化了價格、費率和數量對收入增長的影響。

As mentioned earlier, worldwide revenue grew 20% in constant currency during Q4, driven by strong volume growth of 24%, partially offset by price.

如前所述，在 24% 的強勁銷量增長的推動下，第四季度全球收入按固定匯率計算增長了 20%，部分被價格抵消。

Foreign exchange had a modest impact on revenue growth.

外匯對收入增長的影響不大。

U.S. revenue grew 31% compared to the fourth quarter of 2019 and 7% excluding bamlanivimab.

與 2019 年第四季度相比，美國收入增長了 31%，不包括 bamlanivimab 的收入增長了 7%。

For the base business, volume growth of 11% was led by Trulicity, Taltz and Verzenio.

對於基礎業務，Trulicity、Taltz 和 Verzenio 的銷量增長了 11%。

Pricing was a 5% drag on U.S. revenue growth this quarter driven primarily by increased rates to maintain excellent access; partially offset by modest list price increases, largely for diabetes; and to a lesser extent, by changes to estimates for rebates and discounts for Taltz, which was driven by the access win at ESI.

定價對本季度美國收入增長造成 5% 的拖累，主要是由於提高利率以保持良好的准入；部分被適度的標價上漲所抵消，主要是針對糖尿病；在較小程度上，由於 ESI 獲得訪問權而改變了 Taltz 的回扣和折扣估計值。

Segment mix was not a major driver of U.S. price performance in the fourth quarter as increased utilization in more highly rebated government segments was offset by lower utilization in the 340B segment primarily for Trulicity and Humalog.

細分市場組合併不是第四季度美國價格表現的主要推動力，因為高回扣政府細分市場的利用率增加被主要用於 Trulicity 和 Humalog 的 340B 細分市場的較低利用率抵消。

Like Q4, the full impact of price was also a headwind of 5%, consistent with our 2020 expectations for a mid-single-digit net price decline in the U.S. While the midterm price trends are stable at present, given the increasing variability in payer mix, we expect to see quarterly variability in our U.S. price impact during the course of 2021.

與第四季度一樣，價格的全面影響也是 5% 的逆風，這與我們對 2020 年美國淨價格下降中個位數的預期一致。雖然鑑於付款人的可變性增加，目前中期價格趨勢穩定混合，我們預計在 2021 年期間我們的美國價格影響將出現季度變化。

Moving to Europe.

搬到歐洲。

Revenue grew 12% in constant currency driven by 9% volume growth and a favorable impact from price.

在銷量增長 9% 和價格的有利影響的推動下，按固定匯率計算的收入增長了 12%。

Volume growth was led by Alimta, Trulicity and Taltz.

銷量增長由 Alimta、Trulicity 和 Taltz 引領。

We're pleased with the continued uptake of our key growth products across Europe and are looking forward to continued strong growth in 2021.

我們很高興我們的主要增長產品在歐洲繼續被採用，並期待在 2021 年繼續強勁增長。

In Japan, revenue decreased 10% in constant currency driven primarily by decreased volume in post-patent expiry products, Cialis and Forteo, as well as by a modest pricing headwind due to the government-mandated price decreases that went into effect in March 2020.

在日本，按固定匯率計算，收入下降 10%，主要是由於專利到期後產品 Cialis 和 Forteo 的銷量減少，以及由於政府強制降價導致的適度定價逆風，該政策於 2020 年 3 月生效。

Japan is experiencing the impact of countercyclical patent expiries with Cialis, Strattera and Cymbalta LOEs impacting growth in 2020 and likely in 2021.

日本正在經歷反週期專利到期的影響，Cialis、Strattera 和 Cymbalta LOE 影響了 2020 年甚至 2021 年的增長。

In China, revenue grew 31% in constant currency driven by 57% volume growth driven by Tyvyt and partially offset by pricing concessions for the government-sponsored programs which drove Tyvyt's significant volume growth.

在中國，Tyvyt 推動了 57% 的銷量增長，按固定匯率計算，收入增長了 31%，但部分抵消了推動 Tyvyt 銷量大幅增長的政府資助項目的定價優惠。

We are excited about the momentum of our China oncology business, and we are looking forward to continued growth for Tyvyt and the launch uptake for Verzenio.

我們對中國腫瘤業務的發展勢頭感到興奮，我們期待 Tyvyt 的持續增長和 Verzenio 的推出。

We're also pleased that Trulicity and Olumiant were added to the NRDL as of January 2021.

我們也很高興 Trulicity 和 Olumiant 自 2021 年 1 月起被納入 NRDL。

Revenue in the rest of the world increased 6% in constant currency driven by strong volume from Trulicity and Olumiant as well as 3 percentage points of growth coming from bamlanivimab sales to Canada.

由於 Trulicity 和 Olumiant 的強勁銷量以及 bamlanivimab 對加拿大的銷售增長了 3 個百分點，按固定匯率計算，世界其他地區的收入增長了 6%。

The same information for our full year revenue is at the bottom of the slide.

我們全年收入的相同信息位於幻燈片底部。

As shown on Slide 10, our key growth products continue to drive impressive volume growth.

如幻燈片 10 所示，我們的主要增長產品繼續推動令人印象深刻的銷量增長。

These newer medicines delivered nearly 14 percentage points of growth this quarter, with bamlanivimab also contributing roughly 14 percentage points of growth.

這些較新的藥物本季度實現了近 14 個百分點的增長，其中 bamlanivimab 也貢獻了大約 14 個百分點的增長。

The strong volume growth in our key products was partially offset by post-LOE products as well as by reduced Trajenta royalties from the restructuring of our alliance with Boehringer Ingelheim.

我們主要產品的強勁銷量增長被 LOE 後的產品以及與勃林格殷格翰重組聯盟導致的 Trajenta 特許權使用費減少部分抵消。

This impact will sunset as we move into 2021.

隨著我們進入 2021 年，這種影響將會消失。

Slide 11 highlights the contributions of our key growth products.

幻燈片 11 突出了我們主要增長產品的貢獻。

In total, these brands generated over $3.6 billion in revenue this quarter, making up 55% of our base revenue.

這些品牌本季度的總收入超過 36 億美元，占我們基本收入的 55%。

Amidst the ongoing challenges presented by the pandemic, we are encouraged by the performance of our key growth products in 2020.

在大流行帶來的持續挑戰中，我們對 2020 年主要增長產品的表現感到鼓舞。

Trulicity grew 23%, adding nearly $1 billion last year to finish with over $5 billion in revenue while outgrowing the GLP-1 injectable class in the U.S. and exiting 2020 with a nearly 47% share of total prescriptions amidst the reacceleration of growth for injectable GLP-1s.

Trulicity 增長了 23%，去年增加了近 10 億美元，收入超過 50 億美元，同時超過了美國的 GLP-1 注射劑類別，並且在註射劑 GLP 重新加速增長的情況下，到 2020 年在總處方中的份額接近 47% -1 秒。

Taltz grew 31% to nearly $1.8 billion in revenue, outgrowing the U.S. market in both dermatology and rheumatology and entering 2021 with best-in-class access that provides a strong foundation for long-term growth.

Taltz 的收入增長了 31%，達到近 18 億美元，在皮膚病學和風濕病學領域都超過了美國市場，並在進入 2021 年時以一流的准入為長期增長奠定了堅實的基礎。

Jardiance crossed $1 billion in sales for Lilly's share of revenue in 2020, ending the year at nearly 60% of total SGLT2 prescriptions in the U.S. and driving encouraging growth for the class as we look forward to the regulatory action for HFrEF and the readout for HFpEF this year.

Jardiance 的銷售額在 2020 年為禮來（Lilly）的收入份額超過了 10 億美元，年底占美國 SGLT2 處方總數的近 60%，並推動該類別的令人鼓舞的增長，因為我們期待著對 HFrEF 的監管行動和對 HFpEF 的讀數今年。

And Verzenio revenue grew nearly 60% in 2020 to over $900 million, significantly outgrowing the CDK 4/6 class, growing 6 percentage points in total prescriptions while nearly doubling new-to-brand share of market on the heels of positive data readouts for overall survival in metastatic breast cancer in 2019 and early breast cancer in 2020.

Verzenio 的收入在 2020 年增長了近 60%，達到 9 億美元以上，顯著超過了 CDK 4/6 類別，總處方量增長了 6 個百分點，同時在整體數據顯示積極之後，新品牌的市場份額幾乎翻了一番2019 年轉移性乳腺癌和 2020 年早期乳腺癌的生存率。

Our key growth products will continue to drive Lilly's strong growth outlook in 2021.

我們的主要增長產品將繼續推動禮來公司在 2021 年的強勁增長前景。

On Slide 12, we provide an update on capital allocation.

在幻燈片 12 中，我們提供了資本配置的最新信息。

In 2020, we invested over $8 billion to drive our future growth through a combination of business development, capital expenditures and after-tax investment in R&D.

2020 年，我們投資超過 80 億美元，通過業務發展、資本支出和研發的稅後投資相結合來推動我們的未來增長。

In addition, we returned approximately $3.2 billion to shareholders via dividends and share repurchases.

此外，我們通過股息和股票回購向股東返還了大約 32 億美元。

As mentioned earlier, we also announced a 15% dividend increase for the third consecutive year, demonstrating our confidence in the outlook for the company.

如前所述，我們還宣布連續第三年增加 15% 的股息，表明我們對公司前景充滿信心。

We are focused on utilizing the strong cash flow our business generates to develop the next wave of new medicines through both internal and external sources, as highlighted by the recently completed acquisition of Prevail Therapeutics.

正如最近完成的對 Prevail Therapeutics 的收購所強調的那樣，我們專注於利用我們的業務產生的強勁現金流通過內部和外部資源開發下一波新藥。

We will remain active in assessing bolt-on acquisitions or in-licensing where we can create shareholder value and enhance our future growth prospects.

我們將繼續積極評估附加收購或許可，以創造股東價值並增強我們未來的增長前景。

Turning to our 2021 financial guidance on Slide 13.

轉向我們在幻燈片 13 上的 2021 年財務指導。

We are affirming our non-GAAP guidance, and we've updated our GAAP guidance to reflect the impact of the Precision Biosciences, Merus and Asahi Kasei agreements, which with reported earnings per share for 2021 now expected to be in the range of $7.10 to $7.75.

我們確認我們的非 GAAP 指導，並且我們更新了我們的 GAAP 指導，以反映 Precision Biosciences、Merus 和 Asahi Kasei 協議的影響，根據報告的 2021 年每股收益現在預計在 7.10 美元至7.75 美元。

The impact of the recently completed acquisition of Prevail Therapeutics will be updated on our next quarterly call and will only impact Lilly's GAAP guidance for 2021.

最近完成的 Prevail Therapeutics 收購的影響將在我們的下一個季度電話會議上更新，並且只會影響禮來公司 2021 年的 GAAP 指導。

There will be no change to our 2021 guidance for R&D expense or non-GAAP EPS as a result of this transaction.

由於此次交易，我們對研發費用或非公認會計原則每股收益的 2021 年指導不會發生變化。

As we move into this new year, and as we noted on our guidance call, we continue to experience suppressed demand due to the pandemic with several key therapeutic classes still below our pre-COVID baseline.

隨著我們進入新的一年，正如我們在指導電話中指出的那樣，由於大流行，我們繼續經歷需求抑制，幾個關鍵治療類別仍低於我們在 COVID 之前的基線。

We remain committed to ensuring we are doing our part to limit COVID-19 exposure for physicians, patients and our employees as cases surge in the U.S. and around the world.

隨著美國和世界各地的病例激增，我們仍然致力於確保我們儘自己的一份力量來限制醫生、患者和我們的員工接觸 COVID-19。

At present, most of our HCP interactions in the U.S. and many other major markets are virtual.

目前，我們在美國和許多其他主要市場的大部分 HCP 互動都是虛擬的。

While this may have a near-term impact on new-to-brand performance, we continue to believe our approach is the appropriate posture as we support health care professionals navigating the ongoing pandemic and driving broad vaccination to enable a return to normalcy for health care systems in the second half of the year.

雖然這可能會對新品牌的表現產生近期影響，但我們仍然相信我們的方法是適當的姿態，因為我們支持醫療保健專業人員應對持續的大流行並推動廣泛的疫苗接種，以使醫療保健恢復正常下半年系統。

In addition, our year-end 2020 inventory build was approximately $120 million higher than Q4 2019, which was driven by 2019 having a lower-than-typical year-end stocking.

此外，我們 2020 年年底的庫存建設比 2019 年第四季度高出約 1.2 億美元，這是由於 2019 年年底庫存低於典型水平。

This primarily impacts our diabetes products as well as Taltz and Alimta.

這主要影響我們的糖尿病產品以及 Taltz 和 Alimta。

We anticipate this inventory will burn off in Q1 2021 like normal historical patterns.

我們預計該庫存將像正常的歷史模式一樣在 2021 年第一季度耗盡。

As I noted on our guidance call, we also experienced significant COVID-19-related stocking benefit of roughly $250 million in Q1 2020.

正如我在指導電話中指出的那樣，我們在 2020 年第一季度還經歷了大約 2.5 億美元的與 COVID-19 相關的重大庫存收益。

Given those divergent year-over-year inventory trends, we expect inventory patterns will have a negative impact on revenue growth and operating margin expansion in the first quarter of 2021.

鑑於這些不同的同比庫存趨勢，我們預計庫存模式將對 2021 年第一季度的收入增長和營業利潤率擴張產生負面影響。

Despite these challenges, we remain confident in our full year outlook for 2021 and have increased confidence in our mid- and long-term outlook given our recent high-quality pipeline readouts.

儘管存在這些挑戰，但我們對 2021 年的全年展望仍然充滿信心，並且鑑於我們最近的高質量管道讀數，我們對我們的中長期前景充滿信心。

So now I'll turn the call over to Dan to highlight our progress on R&D.

所以現在我將把電話轉給 Dan 來強調我們在研發方面的進展。

Thanks, Josh.

謝謝，喬希。

We had an exciting start to 2021 as we read out positive results for donanemab in the Phase II TRAILBLAZER-ALZ study.

當我們在 II 期 TRAILBLAZER-ALZ 研究中讀出 donanemab 的積極結果時，我們在 2021 年有了一個激動人心的開始。

Lilly has spent more than 30 years dedicated to finding solutions for Alzheimer's disease, and we are proud of our progress in advancing the science and providing hope for patients and their families suffering from this devastating disease.

禮來 (Lilly) 花了 30 多年的時間致力於尋找阿爾茨海默病的解決方案，我們為我們在推進科學和為患有這種毀滅性疾病的患者及其家人帶來希望方面取得的進展感到自豪。

On Slide 14, you can see our key takeaways from this exciting trial.

在幻燈片 14 上，您可以看到我們從這次激動人心的試驗中獲得的主要收穫。

We are encouraged by the strong efficacy results, where in a relatively small study, we overcame the scale of the study with precision on patient enrollment and a very potent and effective plaque-clearing drug, becoming the first-ever disease modification study to hit statistical significance on its primary endpoint, with a slowing of decline by 32% relative to placebo as measured by the Integrated Alzheimer's Disease Rating Scale.

我們對強大的療效結果感到鼓舞，在一項相對較小的研究中，我們以精確的患者入組和非常有效的斑塊清除藥物克服了研究規模，成為有史以來第一個達到統計學的疾病改變研究根據綜合阿爾茨海默病評定量表，其主要終點的顯著性降低了 32% 相對於安慰劑。

iADRS is a clinical composite tool combining 2 well-accepted measures in Alzheimer's disease: ADAS-Cog-13 for cognition; and ADCS-iADL, instrumental activities of daily living, for function.

iADRS 是一種臨床複合工具，結合了兩種公認的阿爾茨海默病測量方法：用於認知的 ADAS-Cog-13；和 ADCS-iADL，日常生活的工具性活動，用於功能。

While the study was not powered for assessing multiple endpoints, we're very encouraged by the consistent improvements observed on all prespecified secondary endpoints for cognition and function compared to placebo, though donanemab did not reach statistical significance on every secondary endpoint.

雖然該研究無法評估多個終點，但與安慰劑相比，在認知和功能的所有預先指定的次要終點上觀察到的持續改善讓我們感到非常鼓舞，儘管多納奈單抗在每個次要終點上都沒有達到統計學意義。

The consistency across time points and across statistical methods was very encouraging, particularly the disease progression model, which is becoming more accepted by the scientific community.

跨時間點和跨統計方法的一致性非常令人鼓舞，特別是疾病進展模型，它越來越被科學界接受。

In addition, we saw rapid and deep amyloid plaque clearance for donanemab-treated patients who, on average, showed an 84-centiloid reduction of amyloid plaque at 76 weeks compared to a baseline of 108 centiloids.

此外，我們看到接受多那奈單抗治療的患者的澱粉樣蛋白斑塊清除迅速而深入，與基線 108 centiloids 相比，這些患者在 76 週時澱粉樣蛋白斑塊平均減少了 84 centiloids。

Since below 25 centiloids is a negative amyloid scan, this means that the average donanemab-treated patient had a negative scan by the end of the study.

由於低於 25 centiloids 是陰性澱粉樣蛋白掃描，這意味著平均多奈奈單抗治療的患者在研究結束時有陰性掃描。

Finally, the safety profile was consistent with observations from Phase I. Amyloid-Related Imaging Abnormalities, or ARIA, were observed, which is consistent with plaque-clearing antibodies.

最後，安全性與 I 期觀察結果一致。觀察到澱粉樣蛋白相關成像異常或 ARIA，這與斑塊清除抗體一致。

In the donanemab treatment Group, ARIA-E occurred in 27% of treated participants with an overall incidence of 6% of patients experiencing symptomatic ARIA-E.

在多納奈單抗治療組中，27% 的接受治療的參與者出現 ARIA-E，出現症狀性 ARIA-E 的患者的總發病率為 6%。

We look forward to sharing the full results of TRAILBLAZER-ALZ at the AD/PD 2021 virtual meeting on March 13, and we plan to have an investor call at 11 a.m.

我們期待在 3 月 13 日的 AD/PD 2021 虛擬會議上分享 TRAILBLAZER-ALZ 的全部結果，我們計劃在上午 11 點召開投資者電話會議。

on March 15.

3月15日。

We hope to reproduce and extend these exciting findings in our second pivotal donanemab trial, TRAILBLAZER-ALZ 2, an 18-month study which began enrolling patients last year.

我們希望在我們的第二個關鍵多納奈馬試驗 TRAILBLAZER-ALZ 2 中重現和擴展這些令人興奮的發現，這是一項為期 18 個月的研究，於去年開始招募患者。

At present, the study is expected to complete enrollment later this year with nearly twice as many patients as the first TRAILBLAZER trial.

目前，該研究預計將在今年晚些時候完成入組，患者人數幾乎是第一次 TRAILBLAZER 試驗的兩倍。

We'll be engaging regulators to finalize the patient numbers and statistical plans for TRAILBLAZER 2, and we hope the exciting results from TRAILBLAZER 1 will increase patient interest and expedite enrollment.

我們將與監管機構合作，以最終確定 TRAILBLAZER 2 的患者人數和統計計劃，我們希望 TRAILBLAZER 1 的令人興奮的結果將增加患者的興趣並加快註冊。

TRAILBLAZER 2 was designed last year prior to TRAILBLAZER 1 data.

TRAILBLAZER 2 是在去年 TRAILBLAZER 1 數據之前設計的。

And while the design is similar, at that time, we incorporated a few differences, including CDR Sum of the Boxes was moved to the primary endpoint for this larger trial, while iADRS becomes a key secondary endpoint.

雖然設計相似，但當時我們合併了一些差異，包括 CDR Sum of the Boxes 被移至這個更大試驗的主要終點，而 iADRS 成為關鍵的次要終點。

We added a high-tau group.

我們添加了一個高 tau 組。

And we include a blood-based screening for enrollment using the p-tau biomarker.

我們還包括使用 p-tau 生物標誌物進行的基於血液的登記篩查。

We look forward to sharing the TRAILBLAZER-ALZ data and discussing next step for donanemab with regulators.

我們期待與監管機構分享 TRAILBLAZER-ALZ 數據並討論 donanemab 的下一步。

Moving to Slide 15.

轉到幻燈片 15。

As we discussed in-depth on Tuesday's call, there have been a number of developments for our COVID-19 antibodies since our last earnings call, which I will highlight only briefly now.

正如我們在周二的電話會議上深入討論的那樣，自上次財報電話會議以來，我們的 COVID-19 抗體已經取得了一些進展，我現在只簡要強調一下。

In November, the FDA granted emergency use authorization for bamlanivimab as a treatment for COVID-19.

11 月，FDA 授予了 bamlanimab 作為 COVID-19 治療藥物的緊急使用授權。

We also submitted a request for EUA for bamlanivimab and etesevimab together, which remains under review based on Phase II data from the BLAZE 1 trial.

我們還同時提交了 bamlanivimab 和 etesevimab 的 EUA 請求，該請求仍在根據 BLAZE 1 試驗的 II 期數據進行審查。

Since the EUA for bamlanivimab, we've shipped approximately 1 million doses, and we'll have over 1 million additional doses available through mid-2021 for use around the world.

自 bamlanivimab 的 EUA 以來，我們已經運送了大約 100 萬劑，到 2021 年年中，我們將有超過 100 萬劑可供全球使用。

This week, the U.S. government committed to purchase 500,000 of those additional doses by the end of March.

本週，美國政府承諾在 3 月底之前購買 500,000 劑這些額外劑量。

Should an EUA be granted for bamlanivimab and etesevimab together, we expect to be able to supply, in collaboration with Amgen, up to 1 million doses of etesevimab for administration with bamlanivimab together by mid-2021, with 250,000 doses available already in the first quarter this year.

如果 bamlanivimab 和 etesevimab 一起獲得 EUA，我們預計將能夠與 Amgen 合作，在 2021 年中期之前提供多達 100 萬劑 etesevimab 與 bamlanivimab 一起給藥，第一季度已經有 250,000 劑可用今年。

In just the past 8 days, we've shared Phase III data from the BLAZE-2 prevention trial, where bamlanivimab showed up to an 80% reduction of risk of COVID-19 for nursing home residents; Phase III data from the BLAZE-1 trial for etesevimab together with bamlanivimab, which showed a 70% reduction in hospitalization or death among high-risk COVID-19 patients, providing further support for the EUA request for their joint administration.

在過去的 8 天裡，我們分享了 BLAZE-2 預防試驗的 III 期數據，其中 bamlanivimab 顯示療養院居民感染 COVID-19 的風險降低了 80%；來自 etesevimab 和 bamlanivimab 的 BLAZE-1 試驗的 III 期數據顯示，高危 COVID-19 患者的住院或死亡減少了 70%，為 EUA 對其聯合給藥的要求提供了進一步的支持。

Importantly, there were no COVID-19-related deaths in the antibody treatment arms from these 2 pivotal data sets.

重要的是，從這兩個關鍵數據集中，抗體治療組中沒有與 COVID-19 相關的死亡。

After having seen these results, Lilly has decided we will no longer conduct placebo-controlled studies in high-risk patients.

看到這些結果後，禮來決定不再對高危患者進行安慰劑對照研究。

Initial results from the ongoing BLAZE-4 Phase II trial provide viral load and PK/PD data which demonstrated that lower doses, including bamlanivimab 700 milligrams and etesevimab 1,400 milligrams together, are similar to the 2,800 milligram doses of those antibodies administered together.

正在進行的 BLAZE-4 II 期試驗的初步結果提供了病毒載量和 PK/PD 數據，這些數據表明，包括 700 毫克 bamlanivimab 和 1,400 毫克的 etesevimab 在內的較低劑量與這些抗體的 2,800 毫克劑量相似。

We expanded the BLAZE-4 trial to also evaluate the administration of bamlanivimab with VIR-7831 in collaboration with Vir and GSK, reinforcing our commitment to collaborate across the industry to treat current and future strains of COVID-19.

我們擴大了 BLAZE-4 試驗，還與 Vir 和 GSK 合作評估了 Bamlanimab 與 VIR-7831 的管理，加強了我們在整個行業合作治療當前和未來 COVID-19 菌株的承諾。

And yesterday, we received authorization from the FDA to update preparation and administration instructions in response to feedback from frontline nurses and doctors to enable flexibility which can reduce infusion times considerably.

昨天，我們獲得了 FDA 的授權，可以根據一線護士和醫生的反饋更新製備和給藥說明，以實現靈活性，從而大大減少輸液時間。

These updates can shorten infusion times to as little as 16 minutes.

這些更新可以將輸液時間縮短至 16 分鐘。

We're pleased with the potential impact our neutralizing antibodies can have, and we're working diligently to make them available to patients around the world.

我們對我們的中和抗體可能產生的潛在影響感到高興，我們正在努力使它們可供世界各地的患者使用。

While the exciting progress with donanemab and the COVID-19-neutralizing antibodies has dominated Lilly's news in the past few weeks, we have continued to robustly advance the rest of our pipeline.

儘管過去幾週多納奈單抗和 COVID-19 中和抗體取得的令人興奮的進展主導了禮來（Lilly）的新聞，但我們繼續大力推進我們的其餘管道。

Slide 16 shows select pipeline opportunities as of January 27.

幻燈片 16 顯示了截至 1 月 27 日的選定管道機會。

Positive movement since our last earnings call includes: The submissions Dave noted for Jardiance and Verzenio; the submission of Olumiant for the treatment of COVID-19 in Japan; the initiation of a Phase III trial for empagliflozin in post-myocardial infarction patients; the movement of 2 pain assets into Phase II; and the introduction of 8 new Phase I assets, including our first clinical assets from 2 new modalities for Lilly, the siRNA molecule, ANGPTL3 from our collaboration with Dicerna and 2 gene therapy molecules from Prevail.

自上次財報電話會議以來的積極進展包括： Dave 為 Jardiance 和 Verzenio 提出的意見；在日本提交用於治療 COVID-19 的 Oluminant；在心肌梗死後患者中啟動恩格列淨的 III 期試驗；將 2 個疼痛資產轉移到第二階段；並引入 8 項新的 I 期資產，包括來自禮來公司的 2 種新模式的首個臨床資產、siRNA 分子、我們與 Dicerna 合作的 ANGPTL3 和 Prevail 的 2 種基因治療分子。

In fact, we ended 2020 with a total of 17 new Phase I starts for the year, surpassing 2019's total of 16 first human doses, which was the highest number of new clinical starts for Lilly in a decade.

事實上，我們在 2020 年結束時共有 17 個新的 I 期啟動，超過了 2019 年的 16 個首次人體劑量，這是禮來十年來新臨床啟動的最高數量。

Considering the significant challenges we faced in 2020, including temporarily stopping the initiation of new clinical studies, this is a remarkable achievement.

考慮到我們在 2020 年面臨的重大挑戰，包括暫時停止啟動新的臨床研究，這是一項了不起的成就。

It speaks to the resilience and determination of our R&D organization during challenging times.

它說明了我們研發組織在充滿挑戰的時期的韌性和決心。

Moving to Slide 17.

轉到幻燈片 17。

We show a final tally of how we finished 2020 versus the key events that we expected to occur.

我們展示了我們如何完成 2020 年與我們預期會發生的關鍵事件的最終統計。

Since our guidance call in mid-December, we had submissions for selpercatinib for non-small cell lung cancer in Japan, Jardiance for heart failure for reduced ejection fraction in the United States and Verzenio for early breast cancer in the United States.

自 12 月中旬我們的指導電話會議以來，我們在日本提交了用於治療非小細胞肺癌的 selpercatinib，在美國提交了用於治療射血分數降低的心力衰竭的 Jardiance 和用於美國早期乳腺癌的 Verzenio。

The sea of blue checkmarks emphasizes the sheer quantity of pipeline advancements in 2020.

藍色複選標記的海洋強調了 2020 年管道進步的絕對數量。

However, my takeaway from the year past is that I'm delighted with the quality represented here, including potentially practice-changing data for type 2 diabetes, for hematologic tumors, for early breast cancer, the launch of a first-in-class RET inhibitor as well as the emergency use authorizations for 2 medicines to help address the COVID-19 pandemic.

然而，我對過去一年的看法是，我對這裡展示的質量感到高興，包括可能改變實踐的 2 型糖尿病、血液腫瘤、早期乳腺癌、推出一流的 RET抑製劑以及 2 種藥物的緊急使用授權，以幫助應對 COVID-19 大流行。

We're proud of the significant achievements delivered in 2020.

我們為 2020 年取得的重大成就感到自豪。

As we transition into 2021, I'd like to note that Josh Bilenker will be leaving his position as CEO of Loxo Oncology at Lilly to explore other interests and endeavors.

隨著我們過渡到 2021 年，我想指出 Josh Bilenker 將離開他在禮來公司 Loxo Oncology 的首席執行官一職，以探索其他興趣和努力。

We're grateful to Josh for his contributions to human health, both at Loxo and in his time with Lilly.

我們感謝 Josh 在 Loxo 和在禮來公司期間對人類健康所做的貢獻。

We look forward to working with him in a consulting role.

我們期待與他一起擔任諮詢職務。

I'm very pleased to announce that Jacob Van Naarden is assuming the CEO role, continuing to work alongside Nisha Nanda and David Hyman, ensuring leadership continuity and maintaining the strategy and operating model for Loxo Oncology at Lilly.

我很高興地宣布，Jacob Van Naarden 將擔任首席執行官一職，繼續與 Nisha Nanda 和 David Hyman 一起工作，確保領導層的連續性，並維持禮來 Loxo Oncology 的戰略和運營模式。

Jake is a very highly talented leader, and this move allows him to continue to grow his responsibilities for the benefit of Lilly and Loxo.

Jake 是一位非常有才華的領導者，這一舉措使他能夠繼續履行職責，為 Lilly 和 Loxo 謀福利。

Moving to Slide 18.

轉到幻燈片 18。

You can see the expected events for 2021, including the donanemab data and upcoming disclosure I previously mentioned.

你可以看到 2021 年的預期事件，包括我之前提到的 donanemab 數據和即將披露的信息。

A number of other major readouts are expected this year, including: The remainder of the tirzepatide Phase III program, where we are looking forward to building on the SURPASS 1 data we disclosed late last year; the Phase II readout for zagotenemab, our anti-tau antibody for early Alzheimer's, in a trial similar in design to the TRAILBLAZER trial that just read out; several potential Phase III readouts in immunology; and the results of empagliflozin for HFpEF.

預計今年還有許多其他主要讀數，包括： tirzepatide III 期計劃的其餘部分，我們期待在去年年底披露的 SURPASS 1 數據的基礎上進一步發展； zagotenemab 的 II 期讀數，我們用於早期阿爾茨海默氏症的抗 tau 抗體，在設計上與剛剛讀出的 TRAILBLAZER 試驗相似的試驗中；免疫學中幾個潛在的 III 期讀數；以及恩格列淨治療 HFpEF 的結果。

Based on the recent high-quality pipeline data readouts for donanemab, tirzepatide and LOXO-305, we enter 2021 optimistic by the impact these optimists -- these assets could have on patients.

根據最近對 donanemab、tirzepatide 和 LOXO-305 的高質量管道數據讀數，我們對這些樂觀主義者的影響感到樂觀——這些資產可能對患者產生影響。

And we're focused on discovering and developing more new medicines to help patients.

我們專注於發現和開發更多新藥來幫助患者。

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

現在我把電話轉回給戴夫做一些結束語。

Well, thanks, Dan.

嗯，謝謝，丹。

Before we go to Q&A, let me briefly sum up the progress we made in 2020.

在進行問答之前，讓我簡單總結一下我們在 2020 年取得的進展。

2020 was a remarkable year as Lilly worked to fulfill its purpose in new and important ways.

2020 年是非凡的一年，禮來公司致力於以新的重要方式實現其目標。

In addition to many contributions in the fight against the global pandemic, our business grew 10% in 2020 driven by strong volume growth from our key growth products launched since 2014.

除了在抗擊全球大流行病方面做出的許多貢獻外，我們的業務在 2020 年增長了 10%，這得益於我們自 2014 年以來推出的主要增長產品的強勁銷量增長。

These products now account for more than half of our revenue for the first time.

這些產品現在首次占我們收入的一半以上。

We continued our productivity journey, delivering nearly 300 basis points of operating margin expansion for our base business.

我們繼續我們的生產力之旅，為我們的基礎業務實現了近 300 個基點的營業利潤率擴張。

We made significant progress on our innovation-based strategy with LOXO-305, tirzepatide and Verzenio early breast cancer readouts delivering potential category-changing data, while January's donanemab top line success was a first in Alzheimer's.

我們在基於創新的戰略上取得了重大進展，LOXO-305、tirzepatide 和 Verzenio 早期乳腺癌讀數提供了潛在的類別變化數據，而 1 月份的 donanemab 頂線成功是阿爾茨海默氏症的第一次。

With EUAs for bamlanivimab and Olumiant to combat COVID-19 and bolt-on acquisitions of Dermira and Prevail book-ending the year, the past 12 months have been an exceptional example of Lilly's success in leveraging internal and external innovation.

隨著 bamlanivimab 和 Olumiant 抗擊 COVID-19 的 EUA 以及年底對 Dermira 和 Prevail 的收購，過去 12 個月是禮來在利用內部和外部創新方面取得成功的一個特殊例子。

We returned nearly $3.2 billion to shareholders via the dividend and share repurchase.

我們通過股息和股票回購向股東返還了近 32 億美元。

And we will have another meaningful dividend increase, which we announced in December, reflecting significant confidence in the ongoing strength of our business.

我們將在 12 月宣布另一次有意義的股息增加，這反映了對我們業務持續實力的極大信心。

All of this was accomplished against the headwind of a pandemic that is still raging.

所有這一切都是在一場仍在肆虐的大流行的逆風中完成的。

While the new year does not free us from that near-term challenge, our long-term outlook has never been stronger.

雖然新的一年並沒有讓我們擺脫近期的挑戰，但我們的長期前景從未如此強勁。

This concludes the prepared remarks, and I'll turn the call over to Kevin for the Q&A.

準備好的評論到此結束，我將把電話轉給 Kevin 進行問答。

Thanks, Dave.

謝謝，戴夫。

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

（操作員說明）Toni，請提供問答環節的說明，然後我們為第一個來電者做好準備。

(Operator Instructions) Our first question comes from the line of Geoff Meacham with Bank of America.

（操作員說明）我們的第一個問題來自美國銀行的 Geoff Meacham。

Just have a couple.

就來一對吧。

Dan, on donanemab, I know you're planning on having regulatory discussions, but beyond expanding TRAILBLAZER-ALZ 2, is it reasonable to start a third study just to expand the safety database and the treatment experience?

Dan，關於 donanemab，我知道您正計劃進行監管討論，但除了擴大 TRAILBLAZER-ALZ 2 之外，僅僅為了擴大安全性數據庫和治療經驗而開始第三項研究是否合理？

And then, Josh, you mentioned you're still seeing commercial impact from COVID.

然後，喬希，你提到你仍然看到 COVID 帶來的商業影響。

What would you say are the franchises that were mostly affected in 2020?

您認為 2020 年受影響最大的特許經營權是什麼？

And maybe just review your assumptions for normalization of some of those in 2021.

也許只是回顧一下你對 2021 年一些假設的正常化的假設。

Thanks, Jeff.

謝謝，傑夫。

Dan and Josh?

丹和喬什？

Got it.

知道了。

Thanks, Jeff.

謝謝，傑夫。

Your question is whether we'd consider starting a third donanemab study to improve the safety database.

您的問題是我們是否會考慮開始第三次 donanemab 研究以改進安全數據庫。

No, we haven't considered that at present.

不，我們目前還沒有考慮到這一點。

Of course, as we said, our next step is to discuss the data set we have with regulators.

當然，正如我們所說，我們的下一步是與監管機構討論我們擁有的數據集。

I think if we determine that we need more patients, the place to do that is the TRAILBLAZER-2 study.

我認為，如果我們確定需要更多患者，那麼可以進行 TRAILBLAZER-2 研究。

With respect to additional studies, I think there could be opportunities to explore other populations, and we're working through those possibilities right now, but we don't see that necessary for this current population.

關於其他研究，我認為可能有機會探索其他人群，我們現在正在研究這些可能性，但我們認為對於目前的人群來說沒有必要。

Thanks, Jeff.

謝謝，傑夫。

I think when we look across our therapeutic areas, it's relatively consistent at this point that we're still not quite back to new-to-brand prescriptions in key areas like immunology, pain and diabetes, although the diabetes numbers are looking stronger as we get here into January.

我認為，當我們縱觀我們的治療領域時，在這一點上相對一致的是，我們在免疫學、疼痛和糖尿病等關鍵領域還沒有完全恢復到新品牌處方，儘管隨著我們的糖尿病人數看起來越來越多一月份到這裡。

But I think we're still seeing some suppressed demand.

但我認為我們仍然看到一些需求受到抑制。

Physicians have, I think, in most markets, have figured out how to see patients safely and we're seeing nothing like what we saw back in April and May in the U.S. So I think we just have to be cautious as we get into the first quarter and realize that the more complex treatments have some higher degree of variability against them.

我認為，在大多數市場，醫生已經知道如何安全地看病，而我們在美國看到的情況與 4 月和 5 月不同。所以我認為我們在進入第一季度，並意識到更複雜的治療對它們有更高程度的可變性。

And that includes starting new patients in areas like migraine.

這包括在偏頭痛等領域開始新患者。

I think maintenance has been good throughout the pandemic.

我認為整個大流行期間的維護都很好。

So we do expect that as we get through the first half of this year, we'll see return to fully normal levels.

因此，我們確實預計，隨著我們度過今年上半年，我們將看到恢復到完全正常的水平。

But I think it's fair to assume that in the first quarter, we'll still be, in many of the therapeutic areas, a little bit below pre-COVID baselines in terms of new prescription starts.

但我認為可以公平地假設，在第一季度，在許多治療領域，就新處方開始而言，我們仍將略低於 COVID 之前的基線。

Probably worth mentioning, Jeff, as well, derm, because I think that one also, you see some suppression in new patient starts.

可能值得一提的是，傑夫，還有皮膚，因為我認為還有一個，你會在新患者開始時看到一些抑制。

Not affecting our share or anything, but just the overall volume in the category.

不會影響我們的份額或任何東西，而只會影響該類別的整體數量。

Our next question comes from Tim Anderson with Wolfe Research.

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

A couple on donanemab.

一對夫婦在 donanemab 上。

Investors are naturally wondering what the odds are that you could file for approval based on this first Phase II trial.

投資者自然想知道，根據第一次 II 期試驗，您可以申請批准的可能性有多大。

To me, it seems highly unlikely given the size of the trial and the different subgroups.

對我來說，考慮到試驗的規模和不同的亞組，這似乎不太可能。

But just wondering if you can share your latest thoughts on that.

但只是想知道您是否可以分享您對此的最新想法。

And then, Dan, your view of the need to continue to knock down what is sometimes described in the industry as toxic oligomers, which is what you might achieve by giving monoclonals chronically well after patients have already seen plaque normalization.

然後，Dan，您認為需要繼續消除行業中有時被描述為有毒低聚物的物質，這是您在患者已經看到斑塊正常化後長期給予單克隆抗體可能實現的目標。

Thanks, Tim.

謝謝，蒂姆。

We'll go to Dan for both of those.

我們會去丹為這兩個。

Great.

偉大的。

Tim.

蒂姆。

So your first question is on the possibility of approval from a single study in Alzheimer's disease.

所以你的第一個問題是關於阿爾茨海默病單項研究獲得批准的可能性。

Look, we -- in general, we don't disclose our back and forth with FDA or other regulators.

看，我們——一般來說，我們不會與 FDA 或其他監管機構來回披露我們的信息。

In this case, of course, we've said that next steps are discussions with regulators.

當然，在這種情況下，我們已經說過下一步是與監管機構進行討論。

So clearly, that hasn't happened yet.

很明顯，這還沒有發生。

Still, we understand the regulatory threshold traditionally has been adequate in well-controlled trials.

儘管如此，我們了解監管閾值傳統上在控制良好的試驗中是足夠的。

That means more than one trial.

這意味著不止一次的試驗。

In this case, we have a single adequate and well-controlled trial in Alzheimer's disease.

在這種情況下，我們對阿爾茨海默病進行了一項充分且對照良好的試驗。

That, as I said, has not been the standard in this area.

正如我所說，這不是該領域的標準。

Of course, in other disease areas, notably in oncology.

當然，在其他疾病領域，尤其是腫瘤學領域。

Drugs can be approved from a single trial.

藥物可以通過一次試驗獲得批准。

Usually, that's an accelerated approval.

通常，這是一個加速批准。

Usually, it's a group that's well-defined by pathologic characteristics and biomarkers.

通常，這是一個由病理特徵和生物標誌物明確定義的組。

Usually, there's dramatic pathologic response as well as clinical outcomes.

通常，會有顯著的病理反應和臨床結果。

Of course, that's also true in the case of this donanemab trial.

當然，在這個多納奈單抗試驗的情況下也是如此。

But again, oncology is quite different than Alzheimer's disease.

但同樣，腫瘤學與阿爾茨海默病完全不同。

Your second question was on -- the question of toxic oligomers.

你的第二個問題是關於有毒低聚物的問題。

It's long been unclear what is the toxic species of Abeta.

長期以來一直不清楚 Abeta 的有毒物種是什麼。

Is it monomers?

是單體嗎？

Is it oligomers?

是低聚物嗎？

Is it plaques?

是斑塊嗎？

This antibody was designed to be exquisitely specific for amyloid plaques.

這種抗體被設計為對澱粉樣斑塊具有極強的特異性。

We don't think it finds oligomers.

我們認為它找不到低聚物。

And thereby, the efficacy -- therefore, the efficacy we see here seems to imply that it's the plaques that are the toxic species rather than the oligomers.

因此，功效——因此，我們在這裡看到的功效似乎暗示著斑塊是有毒物質而不是低聚物。

However, we can't rule out that these 2 things are in equilibrium with each other, and perhaps by clearing plaques, you remove oligomers as well.

但是，我們不能排除這兩種物質相互平衡，也許通過清除斑塊，您也可以去除低聚物。

Next question comes from the line of Umer Raffat with Evercore.

下一個問題來自於 Evercore 的 Umer Raffat。

Dan, in the prior studies, the iADRS endpoint, the composite that you used in donanemab, it didn't correlate very well with CDR Sum of the Boxes.

Dan，在之前的研究中，iADRS 終點，即您在 donanemab 中使用的複合材料，它與 CDR 總和的相關性不是很好。

But I did find it interesting that the most recent EXPEDITION3 trial for solanezumab did have high concordance between this new composite versus CDR Sum of the Boxes.

但我確實發現有趣的是，最近針對 solanezumab 的 EXPEDITION3 試驗確實在這種新的複合材料與 CDR Sum of the Boxes 之間具有高度的一致性。

I guess what I'm wondering is, how should we be thinking about whether iADRS versus CDR Sum of the Boxes correlates closely or not?

我想我想知道的是，我們應該如何考慮 iADRS 與 CDR Sum of the Boxes 是否密切相關？

Or is it more a function of the more recent trials where CDR does in fact correlate very closely with iADRS?

或者它更多是最近的試驗的一個功能，其中 CDR 實際上與 iADRS 密切相關？

And I'm thinking about that heading into your donanemab trial.

我正在考慮進入你的 donanemab 試驗。

The other one I had is you have this tau antibody Phase III coming up this year.

我有的另一個是今年你有這個 tau 抗體 III 期。

Maybe if you could remind us, how is this tau-mab similar or different than some of the other ones?

也許如果你能提醒我們，這種 tau-mab 與其他一些有何相似或不同？

Because the progress on this target has not been quite good to date, and I saw your trial was pushed out a little bit as well.

因為目前這個目標的進展不是很好，而且我看到你的試驗也被推遲了一點。

But it would be very helpful to have any color.

但是有任何顏色都會很有幫助。

Thanks, Umer.

謝謝，烏默爾。

Dan?

擔？

Great, thanks.

太謝謝了。

Umer, for your first question on iADRS and its correlation with CDR.

Umer，關於 iADRS 及其與 CDR 的相關性的第一個問題。

Look, when we think about an endpoint for any clinical trial, there's really 2 things that make an endpoint -- a good endpoint.

看，當我們考慮任何臨床試驗的終點時，確實有兩件事可以構成終點——一個好的終點。

One is the statistical validation behind it.

一是其背後的統計驗證。

So in other words, is it reliable across different patients, across different time points, across different trials?

換句話說，它在不同的患者、不同的時間點、不同的試驗中是否可靠？

We put together a lot of data that support that.

我們收集了大量支持這一點的數據。

Second, is it meaningful for patients.

其次，對患者是否有意義。

And in this course -- case, of course, we believe that, that's inherently true.

在本課程中——當然，我們相信，這在本質上是正確的。

This is a composite of 2 things that are widely used, both thought to be important and meaningful, ADAS-Cog and activities of daily living.

這是被廣泛使用的 2 個事物的組合，兩者都被認為是重要且有意義的，ADAS-Cog 和日常生活活動。

Obviously, activities of daily living inherently meaningful for patients.

顯然，日常生活活動對患者而言具有內在意義。

Now why do we pick iADRS versus CDR to be the primary outcome of the study?

現在為什麼我們選擇 iADRS 與 CDR 作為研究的主要結果？

That should be obvious.

這應該是顯而易見的。

It's because we believe that iADRS would be more sensitive for measuring decline, and therefore, more sensitive for measuring a drug effect.

這是因為我們認為 iADRS 對測量下降更敏感，因此對測量藥物效果更敏感。

That's based on all of that statistical validation data that we did.

這是基於我們所做的所有統計驗證數據。

If iADRS and CDR Sum of the Boxes were perfectly well correlated, then iADRS couldn't be better, it couldn't be more powerful.

如果 iADRS 和 CDR Sum of the Boxes 完全相關，那麼 iADRS 再好不過了，它再強大也再好不過了。

And yet, I'm telling you that our assumption going into this trial was that it would be.

然而，我要告訴你，我們在進行這次試驗時的假設是它會是這樣。

So of course, different outcomes will have some correlation, but they won't be perfectly correlated.

所以當然，不同的結果會有一些相關性，但它們不會完全相關。

Based on what we saw in this trial, I think we haven't changed our thinking on outcomes.

根據我們在這次試驗中看到的情況，我認為我們沒有改變對結果的看法。

And we still think iADRS is a very valid and important outcome for Alzheimer's trials.

我們仍然認為 iADRS 是阿爾茨海默氏症試驗的一個非常有效和重要的結果。

Of course, that's a discussion to be had with regulators and the scientific community.

當然，這需要與監管機構和科學界進行討論。

With respect to zagotenemab, this is our anti-tau antibody.

關於 zagotenemab，這是我們的抗 tau 抗體。

Just as donanemab was a different type of anti-amyloid beta based on its specificity for plaques, zagotenemab is a different kind of anti-tau antibody.

正如 donanemab 是基於其對斑塊的特異性的不同類型的抗澱粉樣蛋白 β 一樣，zagotenemab 是一種不同類型的抗 tau 抗體。

It's highly specific for aggregated tau.

它對聚合的 tau 具有高度特異性。

Now we think that's particularly important in the case of tau because there's a lot of soluble monomeric tau.

現在我們認為這在 tau 的情況下尤為重要，因為有很多可溶性單體 tau。

And tau antibodies, like any other antibody, not much of it gets in the brain.

而 tau 抗體，就像任何其他抗體一樣，不會有多少進入大腦。

So if you have a lot of monomer and a little bit of antibody, it could sop up all of your antibody and not have left to go after what we think is the more important species, aggregated tau.

所以如果你有很多單體和一點點抗體，它可能會吸收你所有的抗體，而不必去追求我們認為更重要的物種，聚合 tau。

So we'll have to wait and see.

所以我們將不得不拭目以待。

Of course, this is a field that is younger than anti-amyloid therapies, but we've taken a lot of things we learned from anti-amyloid, applied them to anti-tau.

當然，這是一個比抗澱粉樣蛋白療法更年輕的領域，但我們已經從抗澱粉樣蛋白中學到了很多東西，並將它們應用於抗 tau。

And we're quite looking forward to getting that data later this year.

我們非常期待在今年晚些時候獲得這些數據。

Our next question comes from the line of Steve Scala with Cowen.

我們的下一個問題來自 Steve Scala 和 Cowen 的對話。

Two questions.

兩個問題。

Investor expectations are quite high for donanemab in terms of sales potential.

就銷售潛力而言，投資者對 donanemab 的期望很高。

Lilly knows the full data for TRAILBLAZER and also the largely failed Abeta antibody landscape better than any other company.

Lilly 比任何其他公司都更了解 TRAILBLAZER 的全部數據以及很大程度上失敗的 Abeta 抗體格局。

Based on what you've said, including that donanemab will be a driver in '25 through '30, it sounds as though you are fully comfortable with these multibillion-dollar expectations.

根據您所說的，包括 donanemab 將成為 25 到 30 年的驅動程序，聽起來您對這些數十億美元的期望完全滿意。

Is that the conclusion you want to leave us with?

這就是你想給我們留下的結論嗎？

Secondly, LOXO-305 looks like it could be best-in-class in oncology, and the safety looks favorable.

其次，LOXO-305看起來可能是腫瘤學中的同類最佳，而且安全性看起來不錯。

Has Lilly ruled out non-oncology indications for 305, potentially MS?

禮來公司是否排除了 305 的非腫瘤適應症，可能是 MS？

Or perhaps for the sister BTK that you also have?

或者也許是為了你也有的妹妹BTK？

Thanks, Steve.

謝謝，史蒂夫。

We'll go to Dave for the first question and then Dan for the second one.

第一個問題我們先去找 Dave，然後再找 Dan 回答第二個問題。

Yes.

是的。

Steve, I mean, we don't comment on analyst models or forecast, and we never would.

史蒂夫，我的意思是，我們不對分析師模型或預測發表評論，而且我們永遠不會。

So I can't directly answer your question.

所以我不能直接回答你的問題。

I guess what I can say is we've invested in Alzheimer's for 30-plus years and spent a lot of money, as you point out, mostly failing, because there's a huge unmet medical need, and we believe that investment is justified based on the size of market.

我想我能說的是，我們已經在阿爾茨海默氏症上投資了 30 多年，並且花了很多錢，正如你所指出的，大部分都失敗了，因為有巨大的醫療需求未得到滿足，我們相信投資是合理的，基於市場規模。

But we're not able to say today, donanemab is the answer, has a path to market, et cetera.

但我們今天不能說，donanemab 是答案，有一條通往市場的道路，等等。

We're not saying any of that.

我們不是在說這些。

We're looking forward to the AD/PD presentation coming up.

我們期待即將到來的 AD/PD 演示文稿。

The field will survey that data and make their own conclusions, and we need to talk to the FDA in a formal way about the path forward.

該領域將調查這些數據並得出自己的結論，我們需要以正式的方式與 FDA 討論前進的道路。

And then we'll get to sales forecast later.

然後我們將在稍後進行銷售預測。

But it's just not possible to answer a question like the one you asked.

但是像你問的那樣回答一個問題是不可能的。

Thanks, Dave.

謝謝，戴夫。

Dan?

擔？

Okay.

好的。

The second question, more straightforward, LOXO-305 is a really uniquely specific reversible BTK inhibitor with great drug properties.

第二個問題，更直截了當，LOXO-305 是一種真正獨特的特異性可逆 BTK 抑製劑，具有很好的藥物特性。

That's why it's generating such remarkable data in oncology.

這就是為什麼它在腫瘤學中產生如此顯著的數據。

You're asking a question that we've thought a lot about, which is could this also translate to being a highly differentiated molecule in immunology?

你問了一個我們已經思考了很多的問題，這是否也可以轉化為免疫學中的高度分化分子？

I think in this case, we would not pursue the same molecule.

我認為在這種情況下，我們不會追求相同的分子。

I think this is down the road far enough in oncology, this will be an oncology molecule.

我認為這在腫瘤學方面已經走得很遠了，這將是一個腫瘤學分子。

But you raised the question of whether we'd be interested in generating a sister molecule, as you said, for immunology indications.

但是你提出了我們是否有興趣產生一個姐妹分子的問題，正如你所說，用於免疫學適應症。

That's certainly something we are considering.

這當然是我們正在考慮的事情。

Our next question comes from the line of David Risinger with Morgan Stanley.

我們的下一個問題來自摩根士丹利的 David Risinger。

Congrats on the updates.

恭喜更新。

I have 2 questions, please.

我有2個問題，請。

First, when do you expect to have clarity from the FDA on whether Lilly can file with the single small Phase II trial on donanemab?

首先，您希望 FDA 何時能明確禮來公司是否可以提交關於 donanemab 的單一小型 II 期試驗？

And then second, would Lilly consider changing the primary endpoint for TRAILBLAZER 2, which is currently CDR Sum of Boxes?

其次，禮來公司是否會考慮更改 TRAILBLAZER 2 的主要終點，即目前的 CDR Sum of Boxes？

Thanks, Dave.

謝謝，戴夫。

Dan?

擔？

Okay.

好的。

Thanks, Dave.

謝謝，戴夫。

Your first question is on the potential for filing, which I think we addressed before.

你的第一個問題是關於提交的可能性，我認為我們之前已經解決了這個問題。

We haven't had those discussions with the regulators.

我們還沒有與監管機構進行過這些討論。

Of course, we move quickly to understand the data and schedule discussions with regulators around the world.

當然，我們會迅速採取行動以了解數據並安排與世界各地監管機構的討論。

As I said before, the regulatory standard is adequate and well-controlled trials, so 2 trials there.

正如我之前所說，監管標準是充分且控制良好的試驗，因此有 2 項試驗。

But certainly, we'll be interested to hear what regulators say.

但可以肯定的是，我們很想听聽監管機構的意見。

Thank you.

謝謝你。

And the second one is, see the change over the primary endpoint for TRAILBLAZER 2.

第二個是，查看 TRAILBLAZER 2 主要終點的變化。

Oh, yes.

哦是的。

Sorry, Dave.

對不起，戴夫。

So the second question there is would we change the endpoint?

那麼第二個問題是我們會改變端點嗎？

Yes, of course, we can consider it.

是的，當然，我們可以考慮。

I think we look at the totality of data that we get from TRAILBLAZER 1, and that will inform our decisions, as well as conversations with regulators.

我認為我們會查看從 TRAILBLAZER 1 獲得的全部數據，這將為我們的決策以及與監管機構的對話提供信息。

But so far, we haven't seen anything that leads us to make that decision to change it.

但到目前為止，我們還沒有看到任何導致我們做出改變它的決定的事情。

Our next question comes from Terence Flynn with Goldman Sachs.

我們的下一個問題來自高盛的特倫斯弗林。

This is Dan on for Terence.

這是特倫斯的丹。

Just one from us.

只有我們一個。

On LOXO-305, if you could discuss if you believe there's a path to filing for approval on the Phase I/II data.

在 LOXO-305 上，您是否可以討論您是否認為存在申請批准 I/II 階段數據的途徑。

Yes.

是的。

So we'll go to Anne White for that one.

所以我們會去找安妮懷特。

Well, thanks, Terence, for the question.

好吧，謝謝特倫斯的問題。

And we're obviously very excited about the data, both in CLL and MCL.

我們顯然對 CLL 和 MCL 中的數據感到非常興奮。

And so we do have ongoing discussions with the FDA regarding the potential for accelerated approval.

因此，我們確實與 FDA 就加速批准的可能性進行了討論。

Obviously, in this place, the single-arm accelerated approvals for heme malignancies can be challenging.

顯然，在這個地方，血紅素惡性腫瘤的單臂加速批准可能具有挑戰性。

And so that really does require -- is going to require further discussions with regulators.

所以這確實需要 - 需要與監管機構進一步討論。

So we can't commit yet on submissions or timing or which indications.

所以我們還不能就提交或時間或哪些跡像作出承諾。

But be assured that we'll continue those conversations.

但請放心，我們將繼續這些對話。

And we couldn't be more excited about the data, as Dan mentioned.

正如丹所說，我們對這些數據感到非常興奮。

I think this molecule really started as a molecule focused on C481 mutations.

我認為這個分子真正開始是一個專注於 C481 突變的分子。

And then as we saw the data, and the performance in the broader population is remarkable.

然後正如我們看到的數據，在更廣泛的人群中的表現是顯著的。

So we'll keep that with conversations going, and we'll keep you posted.

因此，我們將繼續進行對話，並隨時通知您。

Our next question comes from the line of Chris Schott with JPMorgan.

我們的下一個問題來自摩根大通的 Chris Schott。

Great.

偉大的。

Just one on donanemab and then just one other one.

只有一個在 donanemab 上，然後是另一個。

What are your thoughts on the high-tau population?

您對高 tau 人口有何看法？

I guess just based on what you saw from TRAILBLAZER, is there a strong rationale the drug could also work in some of these patients?

我想僅根據您從 TRAILBLAZER 中看到的情況，該藥物是否有充分的理由也可以在其中一些患者中起作用？

And maybe just give us a sense of what percent of patients in TRAILBLAZER 2 we should expect to come from that group.

也許只是讓我們了解 TRAILBLAZER 2 中我們應該期望來自該組的患者百分比。

Then my second question was just you did make some changes to your 340B program reimbursement last year.

然後我的第二個問題是您去年確實對您的 340B 計劃報銷進行了一些更改。

Maybe just remind us of the scope of that business in your portfolio.

也許只是提醒我們該業務在您的投資組合中的範圍。

And have there been any either challenges or pushbacks with the implementation of that?

在實施過程中是否有任何挑戰或阻力？

And how we should be just kind of thinking about 340B as we go through 2021?

當我們度過 2021 年時，我們應該如何考慮 340B？

Thanks, Chris.

謝謝，克里斯。

We'll go to Dan for the first question and then Josh on 340B.

第一個問題我們先找丹，然後再找 340B 的喬什。

Yes.

是的。

Thank you, Chris, for your question about the high-tau population.

謝謝你，克里斯，關於高 tau 人口的問題。

A notable feature of the TRAILBLAZER trial is that we excluded patients who had too much tau in their brain.

TRAILBLAZER 試驗的一個顯著特點是我們排除了大腦中 tau 過多的患者。

We believe that people who have the highest tau, or it's spread throughout their brain, are past the point of no return, at least for an amyloid-directed therapy.

我們相信，具有最高 tau 的人，或者它在他們的大腦中傳播的人，已經過了不歸路，至少對於澱粉樣蛋白定向治療來說是這樣。

Of course, as we fully analyze this data, and hopefully, even in time for the upcoming presentation, we'll understand what we're seeing in this current data set with respect to baseline tau levels predicting response to therapy.

當然，當我們全面分析這些數據時，希望即使在即將到來的演示中，我們也能了解我們在當前數據集中看到的關於預測治療反應的基線 tau 水平的情況。

As we see that, that could lead us to be either more excited or less excited about including high-tau patients in TRAILBLAZER 2 study.

正如我們所看到的，這可能導致我們對將高 tau 患者納入 TRAILBLAZER 2 研究感到更加興奮或不那麼興奮。

And so that is something that is still very much open.

所以這仍然是非常開放的。

As we see that data and understand it, we could think about changing the design there.

當我們看到這些數據並理解它時，我們可以考慮改變那裡的設計。

In terms of the percent of patients that are impacted here, it sort of depends on how you cut it.

就這裡受影響的患者百分比而言，這有點取決於你如何削減它。

If you start with all of the early Alzheimer's patients, which is mild plus -- mild AD plus MCI, that's about 4.5 million in the U.S. and double that in Europe and Japan combined.

如果你從所有早期阿爾茨海默氏症患者開始，即輕度 AD 加 MCI，在美國大約是 450 萬，是歐洲和日本加起來的兩倍。

Many of those patients will be amyloid-negative, we've shown that before.

其中許多患者將是澱粉樣蛋白陰性的，我們之前已經證明了這一點。

So you take about 1/3 out for that.

因此，您為此花費了大約 1/3。

A small fraction of them will be amyloid-positive but no tau at all.

其中一小部分將是澱粉樣蛋白陽性，但根本沒有 tau。

We didn't include those patients.

我們沒有包括那些患者。

And then a slightly larger fraction will be in that tau-high group.

然後稍大一點的部分將在那個高 tau 組中。

So once you've excluded all those patients, we've said it's sort of 30% to 45% of that mild AD to MCI population that would meet these enrollment criteria in TRAILBLAZER 1.

因此，一旦您排除了所有這些患者，我們已經說過，在 TRAILBLAZER 1 中，有 30% 到 45% 的輕度 AD 到 MCI 人群將滿足這些註冊標準。

Thanks, Dan.

謝謝，丹。

Josh?

喬什？

Chris, on 340B, what we said is if you look over the last 10 years, the 340B segment has been among the fastest-growing, certainly across the industry but for our business as well.

克里斯，關於 340B，我們所說的是，如果您回顧過去 10 年，340B 細分市場一直是增長最快的細分市場之一，當然在整個行業中，但對於我們的業務也是如此。

And it rivals the size of Medicaid in our U.S. business, so about 10% of the business now.

它在我們的美國業務中與醫療補助的規模相媲美，因此現在約佔業務的 10%。

Of course, the change we made was to go back to the legislated intent and to provide the discounts to the actual hospitals that provide care and to exclude contract pharmacies that have grown over time.

當然，我們所做的改變是回到立法意圖，為提供護理的實際醫院提供折扣，並排除隨著時間的推移而增長的合同藥房。

When we look at that business, that's probably about half of the businesses in these contracted pharmacies.

當我們查看該業務時，這可能是這些簽約藥店業務的一半左右。

So that's where we've made the change to not provide the pricing there.

所以這就是我們做出改變的地方，不在那裡提供定價。

Now we do have a process where those contracted pharmacies can apply, and we've said for insulins, as long as they can demonstrate that they're passing on the entire pricing, that they're still eligible to participate.

現在我們確實有一個流程，那些簽約的藥房可以申請，我們已經說過，對於胰島素，只要他們能證明他們正在傳遞整個定價，他們仍然有資格參與。

When we look at all that together, we knew that there -- that's where we implemented in September.

當我們一起查看所有這些時，我們知道那裡 - 這就是我們在 9 月份實施的地方。

We knew there would be challenges, and we're seeing those challenges come.

我們知道會有挑戰，而且我們看到這些挑戰正在到來。

But I think in terms of patient impacts, we haven't seen much yet.

但我認為就患者影響而言，我們還沒有看到太多。

So we're seeing the fact that the discounts aren't being provided as per our change, but we don't think it's impacting patient care at this point.

因此，我們看到沒有根據我們的變更提供折扣的事實，但我們認為目前這不會影響患者護理。

So everything we're seeing so far is consistent with the decision we made.

所以到目前為止，我們所看到的一切都與我們做出的決定一致。

We knew it would be a difficult decision to implement.

我們知道實施這將是一個艱難的決定。

We knew there would be some customer concerns.

我們知道會有一些客戶的擔憂。

We knew there would be legal challenges.

我們知道會有法律挑戰。

But I think what we saw in the fourth quarter is consistent with the guidance we've given for 2021, which is that we would expect this portion of the 340B program to moderate in growth and provide a 2- to 3-point price tailwind for us in 2021.

但我認為我們在第四季度看到的情況與我們為 2021 年給出的指導一致，即我們預計 340B 計劃的這一部分將放緩增長，並為2021年的我們。

So I think we're on track for that at this point.

所以我認為我們在這一點上正在走上正軌。

The next question comes from the line of Seamus Fernandez with Guggenheim.

下一個問題來自古根海姆的 Seamus Fernandez。

So I just wanted to follow up on the one donanemab question, which is, Dan, can you just give us a little bit of color on the magnitude of blinding in this study, given the fact that patients obviously had almost absolute clearing of their amyloid plaques?

所以我只是想跟進一個 donanemab 的問題，即丹，你能否給我們一點關於這項研究中致盲程度的顏色，因為患者顯然幾乎完全清除了他們的澱粉樣蛋白斑塊？

And your confidence that the behavior of the placebo arm was consistent with the benefits of monitoring both tau and amyloid.

您對安慰劑組的行為與監測 tau 蛋白和澱粉樣蛋白的益處一致的信心。

And then the second question, just wanted to get a bit of an update on Verzenio and how Verzenio is tracking relative to your expectations.

然後是第二個問題，只是想了解有關 Verzenio 的一些更新，以及 Verzenio 如何跟踪您的期望。

I think we're starting to see fits and starts, I guess, to some degree in terms of capturing incremental market share.

我想我們開始看到時斷時續，我猜，在某種程度上，在獲取增量市場份額方面。

But directionally, it seems positive.

但從方向上看，它似乎是積極的。

Just trying to get a sense of where Lilly thinks the uptake could go in metastatic disease and then how ultimately an approval of the adjuvant opportunity can impact sales or your market share going forward.

只是想了解 Lilly 認為轉移性疾病的吸收可能在哪裡，然後最終批准佐劑機會如何影響銷售或您未來的市場份額。

Is that really the big driver?

這真的是大司機嗎？

Or are you already seeing meaningful changes in metastatic market share?

或者您是否已經看到轉移性市場份額發生了有意義的變化？

Thanks, Seamus.

謝謝，西莫。

We'll go to Dan for the first question and then Anne for the second.

第一個問題我們先問丹，第二個問安妮。

Yes.

是的。

Thank you, Seamus, for those very thoughtful questions focused on that blinding of the study.

謝謝你，Seamus，感謝那些非常深思熟慮的問題，這些問題集中在研究的盲目性上。

We said before that TRAILBLAZER 1, we carried this study out with the quality that we typically use for regulatory pivotal studies, fully blinded, double-blinded study.

我們在 TRAILBLAZER 1 之前說過，我們以我們通常用於監管關鍵研究、全盲、雙盲研究的質量進行了這項研究。

You raised the possibility that there could be some unintentional unblinding as a result of amyloid clearance.

您提出了澱粉樣蛋白清除可能導致一些無意的揭盲的可能性。

We don't see that, that's possible.

我們看不到，這是可能的。

Patients don't know or feel the clearance of amyloid in their brain directly.

患者不直接知道或感覺大腦中澱粉樣蛋白的清除。

And investigators wouldn't have seen that -- the results of the PET scan themselves.

調查人員不會看到這一點——PET掃描的結果本身。

The other potential in any Alzheimer's study for inadvertent unblinding is ARIA-E.

任何阿爾茨海默氏症研究中無意揭盲的另一個潛力是 ARIA-E。

Because sometimes, that is something that can cause a side effect.

因為有時，這可能會導致副作用。

And we commented on the 6% of patients that had symptomatic ARIA-E or so.

我們評論了有症狀的 ARIA-E 左右的 6% 的患者。

I think that's certainly an important analysis, I think, in every study in Alzheimer's disease, is to look at the drug effect with and without ARIA patients.

我認為這肯定是一項重要的分析，我認為，在每項阿爾茨海默病研究中，都是觀察有無 ARIA 患者的藥物效應。

And certainly, that's something that we hope to have complete and be able to share in March.

當然，這是我們希望在三月份完成並能夠分享的內容。

And then finally, you asked about the behavior of the placebo arm.

最後，您詢問了安慰劑組的行為。

That's a great question.

這是一個很好的問題。

Really, when we saw this data, that was the first thing I wanted to look at.

真的，當我們看到這些數據時，這是我想看的第一件事。

Sometimes, when you have small studies that look promising, it's because your placebo arm did worse than typical.

有時，當您的小型研究看起來很有希望時，那是因為您的安慰劑組的表現比典型的差。

And here, we said -- we've communicated a high level of confidence and encouragement based on the data.

在這裡，我們說 - 我們已經根據數據傳達了高度的信心和鼓勵。

So that excludes that possibility.

所以排除了這種可能性。

This placebo arm is not behaving aberrantly.

這個安慰劑組沒有異常行為。

That's not what's driving the effect.

這不是驅動效果的原因。

Again, we'll get into the details of that in March, but very, very pleased with the performance of the placebo arm here.

同樣，我們將在 3 月份詳細介紹，但對安慰劑組的表現非常非常滿意。

Thanks, Dan.

謝謝，丹。

Anne?

安妮？

Yes.

是的。

Thanks for the question on Verzenio.

感謝您對 Verzenio 提出的問題。

So as you noted, 2020 was really another year of very positive and clinically meaningful data for Verzenio.

正如您所指出的，對於 Verzenio 而言，2020 年確實是又一個非常積極且具有臨床意義的數據的一年。

And then our shares, as a result, I think, continue to improve.

然後我們的股票，因此，我認為，繼續提高。

While obviously, no CDK is yet approved in the EBC setting, we do think that this readout particularly drew attention to the market class.

雖然顯然，尚未在 EBC 環境中批准 CDK，但我們確實認為該讀數特別引起了市場類別的關注。

So that said, we're really confident that the current trends are a result of our strong execution and our focus on MBC and then the -- particularly the logistically significant OS data which a key competitor in the space didn't have.

話雖如此，我們真的相信當前的趨勢是我們強大的執行力和我們對 MBC 的關注的結果，然後是 - 特別是該領域的主要競爭對手沒有的具有邏輯意義的操作系統數據。

As we compared Q4 '19 to Q4 '20, it was really a remarkable period of growth, as you said, for Verzenio.

當我們將 19 年第四季度與 20 年第四季度進行比較時，正如您所說，對於 Verzenio 來說，這確實是一個顯著的增長時期。

We saw TRx increase of 66%, worldwide revenue growth of 57% and U.S. growth of 36%.

我們看到 TRx 增長了 66%，全球收入增長了 57%，美國增長了 36%。

And what we're hearing pretty repeatedly now from thought leaders is that they're seeing more and more that Verzenio is a differentiated agent.

我們現在從思想領袖那裡反复聽到的是，他們越來越多地看到 Verzenio 是一個差異化的代理人。

So obviously, we've shared that in MBC, we feel we have higher CDK 4/6 activity versus others; differentiated continuous dosing; a monotherapy indication; and then obviously, the data that we saw in MONARCH 2 with the primary endocrine-resistant population.

所以很明顯，我們已經分享了在 MBC 中，我們覺得我們的 CDK 4/6 活動比其他活動更高；差異化連續給藥；單一療法適應症；然後很明顯，我們在 MONARCH 2 中看到的主要內分泌抵抗人群的數據。

So I think all of that is really playing into the growth that we're seeing in the MBC market.

所以我認為所有這些都真正影響了我們在 MBC 市場上看到的增長。

And so we'll expect to continue to see our growth -- our share of market grow in that space.

因此，我們預計將繼續看到我們的增長——我們在該領域的市場份額增長。

On the adjuvant side, as Dave and others mentioned, we did submit to the FDA in other areas at the end of last year.

在佐劑方面，正如 Dave 和其他人提到的，我們確實在去年年底向 FDA 提交了其他領域的申請。

So we look forward to regulatory action later this year.

因此，我們期待今年晚些時候採取監管行動。

This market size is significant in the fact that it's probably an additional 50% if you match our entry criteria, 50% increase to our current metastatic market in this high-risk adjuvant population.

這個市場規模很重要，如果您符合我們的進入標準，它可能會增加 50%，在這個高風險輔助人群中，我們目前的轉移市場增加 50%。

So that's significant.

所以這很重要。

And what's also significant is the duration of treatment will very likely will be longer than in the metastatic setting.

同樣重要的是，治療的持續時間很可能會比轉移環境中的更長。

So patients in the study are treated for 24 months.

因此，研究中的患者接受了 24 個月的治療。

And right now, we're seeing patients staying on for 17-or-more months on average in the study.

現在，我們看到患者在研究中平均停留 17 個月或更長時間。

And many of the patients are still on study, so I think that number will continue to get longer.

許多患者仍在研究中，所以我認為這個數字會繼續增長。

So that duration of treatment offers upside as well.

因此，治療持續時間也有好處。

But we're incredibly excited about the data.

但我們對這些數據感到非常興奮。

We're looking forward to bringing it to patients as soon as possible.

我們期待盡快將其帶給患者。

Thanks for the question.

謝謝你的問題。

Next, we go to the line of Andrew Baum with Citi.

接下來，我們與花旗一起去安德魯鮑姆的路線。

A couple of questions.

幾個問題。

First, on donanemab, on the issue of whether potentially donanemab could be submitted on the back of the Phase II data set that you have.

首先，關於 donanemab，關於潛在的 donanemab 是否可以在您擁有的第二階段數據集的背面提交的問題。

Could you talk to your level of preparedness, particularly manufacturing, given the anticipated demand?

鑑於預期的需求，您能否談談您的準備水平，尤其是製造水平？

But also to the p-tau blood test that will potentially be used to define the patients?

還有可能用於定義患者的 p-tau 血液檢測嗎？

I'm just trying to understand where are you at because there is a scenario by which you could be on the market sooner than perhaps that many may believe.

我只是想了解你在哪裡，因為在這種情況下，你可能會比許多人想像的更早進入市場。

And that's an open observation rather than reflecting any particularly personal view.

這是一個開放的觀察，而不是反映任何特別個人的觀點。

And then second, for Anne.

其次，對於安妮。

Could you talk to your BTK inhibitor 305?

你能和你的BTK抑製劑305談談嗎？

I know you're hiring medical liaisons already, which in hematology, would suggest that you're optimistic about being able to file in the second half.

我知道您已經在招聘醫療聯絡員，這表明您對能夠在下半年提交申請感到樂觀。

From your understanding of the community nature of practice for CLL, given the very high tolerability of this drug and the strong efficacy, even without a randomized trial, do you believe that this drug could take significant market share in the first BTK refractory or intolerant setting?

根據您對 CLL 實踐的社區性質的理解，鑑於這種藥物的極高耐受性和強大的療效，即使沒有隨機試驗，您是否認為這種藥物可以在第一個 BTK 難治或不耐受環境中佔據顯著的市場份額?

Thanks, Andrew.

謝謝，安德魯。

We'll go to Dan for the first question and Anne for the second.

第一個問題我們去找丹，第二個問題找安妮。

Andrew, you raise an excellent question on all the work that needs to be done to prepare for donanemab.

安德魯，你提出了一個很好的問題，關於準備多納奈馬需要做的所有工作。

We actually initiated manufacturing preparedness before we had this data.

我們實際上是在獲得這些數據之前就開始了製造準備工作。

So this is something we do at Lilly, we always prepare for success.

所以這是我們在禮來公司所做的事情，我們總是為成功做準備。

And so at the same time that our manufacturing colleagues were ramping up the anti-COVID antibodies, we asked them to also prepare for donanemab.

因此，在我們的製造同事正在增加抗 COVID 抗體的同時，我們要求他們也為 donanemab 做準備。

So that is well underway, and I like what's going on, the progress we're making in manufacturing there.

所以這一切都在順利進行，我喜歡正在發生的事情，我們在那裡製造方面取得的進展。

The diagnostic ecosystem also needs work.

診斷生態系統也需要工作。

We started that, both ramping up imaging and proceeding along with opportunities to bring the phospho-tau blood test to more patients.

我們開始了這一點，既加大了成像力度，又提供了將磷酸化 tau 血液檢測帶給更多患者的機會。

That's both underway.

這兩者都在進行中。

Again, started before we had this data.

同樣，在我們擁有這些數據之前就開始了。

And that, of course, is useful whether we're successful in coming to market or whether any other anti-amyloid drug comes to market.

當然，無論我們是成功上市還是任何其他抗澱粉樣蛋白藥物上市，這都是有用的。

So those are preparations that we're certainly taking.

所以這些是我們肯定正在採取的準備工作。

Thanks, Dan.

謝謝，丹。

Anne?

安妮？

Yes.

是的。

Thanks for the question on 305.

感謝305的提問。

So with the MSL population, it's important to remember, this arm of our company talks about the work that's going on in our -- across our portfolio.

因此，對於 MSL 人群，重要的是要記住，我們公司的這個部門談論的是我們在我們的投資組合中正在進行的工作。

So this is not just related to 305, but we have other assets in the portfolio that may be heading in this space.

因此，這不僅與 305 有關，而且我們在投資組合中還有其他資產可能會進入這個領域。

So I wouldn't read too much into that.

所以我不會讀太多。

It's normal operations to make sure that we're covering the portfolio.

確保我們覆蓋投資組合是正常操作。

But obviously, they do get many questions about 305, the excitement that's out there in treating physicians.

但很明顯，他們確實收到了很多關於 305 的問題，即治療醫生的興奮。

And importantly, we have a number of large Phase III trials that are starting as well.

重要的是，我們還有許多大型 III 期試驗也正在開始。

And as you know, that field force helps us identify high-quality candidates to include in those programs.

如您所知，該領域的力量幫助我們確定高質量的候選人以包括在這些計劃中。

As far as CLL, obviously, the story there is incredibly exciting, and we do think that we have a real contender here.

就 CLL 而言，顯然，那裡的故事非常令人興奮，我們確實認為我們在這裡有一個真正的競爭者。

And particularly, what we're interested in seeing is what has been seen in the past, certainly in the area of oncology, is that drugs that have a meaningful treatment effect on the same target pathway in patients who have relapsed tend to have, sometimes, an even more pronounced effect in that first-line setting.

特別是，我們有興趣看到的是過去已經看到的，當然在腫瘤學領域，對複發患者的同一靶標通路具有有意義治療效果的藥物往往具有，有時，在第一線設置中的效果更加明顯。

And so that's the upside here that is the potential for LOXO-305, is that first-line setting.

因此，這就是 LOXO-305 的潛力所在，即一線設置。

So this year, we're actually planning to initiate, as you know, 4 global clinical studies, and 3 of them are in CLL.

所以今年，我們實際上計劃啟動 4 項全球臨床研究，其中 3 項是 CLL。

And obviously, 2 of them are in the BTK-pretreated patients, but one is in that -- really is in that head-to-head setting and looking at head-to-head with ibrutinib in CLL.

很明顯，其中 2 人是 BTK 預處理的患者，但其中一個是 - 真的是在那種頭對頭的環境中，並在 CLL 中與依魯替尼進行頭對頭的研究。

And obviously, this is a riskier study to do.

顯然，這是一項風險更大的研究。

We still feel very confident in the later-line setting, but we do have a belief that this molecule has a lot of potential in the first line, and hence, doing the trials.

我們仍然對後線設置非常有信心，但我們確實相信這種分子在第一線具有很大的潛力，因此進行了試驗。

So obviously, as I said earlier, I can't comment on the regulatory likelihood.

很明顯，正如我之前所說，我無法評論監管的可能性。

Those are ongoing conversations with the FDA.

這些是與 FDA 正在進行的對話。

But regardless, we know that in this space, you need randomized clinical trials to really reach the patients that we wish to reach.

但無論如何，我們知道在這個領域，您需要隨機臨床試驗才能真正接觸到我們希望接觸的患者。

And so that's -- the intention is to do those trials, regardless.

所以這就是——不管怎樣，目的是進行這些試驗。

Our next question comes from the line of Gregg Gilbert with Truist Securities.

我們的下一個問題來自 Treist Securities 的 Gregg Gilbert。

On the COVID antibodies, Dave, I realize the latest data is quite fresh.

關於 COVID 抗體，戴夫，我意識到最新數據非常新鮮。

But to the extent you're worried that there could be a disconnect between the power of the data and the speed of uptake, is there anything that Lilly plans to do proactively to help move this along?

但是，如果您擔心數據的力量和吸收速度之間可能存在脫節，禮來公司是否計劃採取主動行動來幫助推動這一進程？

I was intrigued by your comments on the prior call about some well-known hospitals being slower than other hospitals to get trained and ready.

我對您在之前的電話會議上關於一些知名醫院在接受培訓和做好準備方面的速度比其他醫院慢的評論很感興趣。

And I think that was even from before this latest data set.

我認為這甚至是在這個最新數據集之前。

And then maybe for Josh, on that call, it sounded like the upper limit of $2 billion in your guidance is not necessarily set in stone if demand picks up.

然後也許對於喬希來說，在那次電話會議上，如果需求回升，你的指導中 20 億美元的上限聽起來不一定是一成不變的。

What's the practical limitation from a manufacturing standpoint as it relates to 2021 for the antibodies?

從製造的角度來看，與 2021 年抗體相關的實際限制是什麼？

Thanks, Gregg.

謝謝，格雷格。

And we'll go to Dave and then Josh.

我們會去找戴夫，然後是喬希。

Okay.

好的。

Yes, I'll comment.

是的，我會發表評論。

Dan, jump in.

丹，跳進去。

I mean, we've -- since the beginning, we've been working with health care systems and physicians across the country to enable uptake of the antibodies.

我的意思是，我們 - 從一開始，我們就一直在與全國各地的醫療保健系統和醫生合作，以促進抗體的吸收。

I guess it's, in some ways, a test of what happens when you don't have the normal commercial preparation and rollout.

我想，在某些方面，這是對沒有正常商業準備和推出時會發生什麼的測試。

This was done via government channels under an EUA.

這是通過 EUA 下的政府渠道完成的。

And you see big differences in adoption rates, and I highlighted what seems to be an inverse relationship between the places you think about advanced medicine and who's actually using this.

您會看到採用率存在很大差異，我強調了您認為先進醫學的地方與實際使用它的人之間似乎存在反比關係。

One of those barriers clearly is conviction on the data.

這些障礙之一顯然是對數據的信念。

So I'm really pleased with the data we announced in the last week, and I think it will, has to, increase conviction.

所以我對我們上周公布的數據感到非常滿意，我認為這將，必須，增加信念。

And this is also -- there's a class effect here, too.

這也是——這裡也有階級效應。

And the fact that other antibodies are demonstrating promise in different settings adds to that data and I think will build confidence.

其他抗體在不同環境中顯示出前景的事實增加了該數據，我認為這將建立信心。

So hopefully, that will change.

所以希望這會改變。

There's 2 endorsements as well we hope will change: One is NIH, the other is the Infectious Disease Society.

我們希望也有兩個認可會改變：一個是 NIH，另一個是傳染病協會。

That said, there's tons of practical problems with -- at scale infusing people with COVID-19, that have been completely worked out by numerous health systems and not worked out by many, many others.

也就是說，在大規模向人們注入 COVID-19 方面存在大量實際問題，這些問題已被眾多衛生系統完全解決，而許多其他系統並未解決。

So we work quite a bit with state departments of health, et cetera, to share those practices.

因此，我們與州衛生部門等進行了大量合作，以分享這些做法。

The best practice is chart flagging upon positive COVID-19 for at-risk patients, scheduling of appointments, dedicated facilities and staff for high-throughput antibody administration.

最佳實踐是在高危患者的 COVID-19 陽性、預約安排、專用設施和高通量抗體管理工作人員的圖表上進行標記。

Where that's happening, they're using a lot of material.

在發生這種情況的地方，他們使用了大量的材料。

And you can almost see actually a reduction in health care utilization.

你幾乎可以看到醫療保健利用率實際上有所下降。

So we're actually running an experiment like that in New Mexico to actually prove it as well as with UnitedHealthcare.

因此，我們實際上在新墨西哥州進行了一項類似的實驗，以實際證明這一點以及聯合醫療保健公司。

But I'm optimistic that we'll see the rate of use grow.

但我很樂觀，我們會看到使用率增長。

It moved from about 20% in December to about double that now.

它從 12 月的約 20% 上升到現在的兩倍左右。

We hope to see more progress going forward.

我們希望看到更多的進展。

Thanks, Dave.

謝謝，戴夫。

Josh?

喬什？

Yes.

是的。

Thanks, Gregg.

謝謝，格雷格。

So what we've said for this year is guidance range for COVID antibodies is $1 billion to $2 billion.

所以我們今年所說的是 COVID 抗體的指導範圍是 10 億美元到 20 億美元。

And of course, there's a lot of uncertainty in that.

當然，其中有很多不確定性。

Although with what we've announced this morning on the call, the next agreement that we've signed with the U.S. government, that it's probably high probability for $1 billion in the first quarter.

儘管我們今天早上在電話會議上宣布了我們與美國政府簽署的下一個協議，第一季度很可能達到 10 億美元。

That's just the purchase agreements that we already have.

這只是我們已經擁有的採購協議。

I think then to get past that, we have -- based on what we've already committed to in terms of manufacturing, probably about another 500,000 bamlanivimab doses available in the first half of the year in monotherapy and 1 million combo.

我認為，為了克服這一點，我們已經 - 基於我們在製造方面已經承諾的內容，可能在今年上半年再提供 500,000 劑 bamlanivimab 單藥和 100 萬劑組合。

So if we sold all of that and it's weighted heavily towards the U.S. or high-income countries, you could get above $2 billion.

因此，如果我們將所有這些都賣掉，並且主要集中在美國或高收入國家，你可以獲得超過 20 億美元的收益。

But we don't have an EUA with the U.S. government or any other government for the combo yet, and there's a lot to still play out, I think, in terms of vaccine and where these products can be utilized.

但是我們還沒有與美國政府或任何其他政府就該組合達成 EUA，而且我認為，在疫苗和這些產品可以在哪裡使用方面，還有很多事情要做。

If we get into the second half of the year, I think we can continue at the pace of production of million-plus doses available per quarter.

如果我們進入下半年，我認為我們可以繼續以每季度生產數百萬劑的速度進行。

I don't think the manufacturing piece is going to be as much of a barrier in the second half of the year if we stay on the course of vaccines and otherwise.

如果我們繼續在疫苗和其他方面繼續前進，我認為下半年的製造業不會成為太大的障礙。

So clearly, we could be above $2 billion for the year, but there's a lot of uncertainty.

很明顯，我們今年的收入可能超過 20 億美元，但存在很多不確定性。

And we'll continue to monitor this number and provide updates as we have more agreements and more approvals.

隨著我們有更多的協議和更多的批准，我們將繼續監控這個數字並提供更新。

Next, we go to the line of Ronny Gal with Bernstein.

接下來，我們和伯恩斯坦一起去 Ronny Gal 的路線。

Congratulations on nice result, and I will continue in the tradition of asking one question about donanemab and one other.

恭喜您取得了不錯的結果，我將繼續按照關於多拿尼單抗的一個問題和另一個問題的傳統。

So on donanemab, I guess the bar that you can see from the FDA is one kind of well-internally-correlated trial and data support elsewhere.

所以在 donanemab 上，我想你可以從 FDA 看到的酒吧是一種內部相關的試驗和其他地方的數據支持。

When you look at your program, it looks like the support you could provide is from removal of plaque from earlier trials.

當您查看您的程序時，您可以提供的支持似乎是從早期試驗中去除斑塊。

And I guess the question for you is, is the understanding that plaque removal is related to clinical benefit solid enough that you can use that as supporting data?

我想你的問題是，對於斑塊去除與臨床益處相關的理解是否足夠穩固，以至於你可以將其用作支持數據？

Or is the logic for early approval based elsewhere?

還是基於其他地方的早期批准的邏輯？

As for a non-donanemab question, I was going to go back to the 340B prices.

至於非 donanemab 的問題，我打算回到 340B 的價格。

The signs are increasing from D.C. there might be an action on this issue before the end of 2021.

華盛頓特區的跡象正在增加。可能會在 2021 年底之前就這個問題採取行動。

I just want to kind of confirm that you have not assumed in your model, got full impact for the entire year, but there is some sort of a partial year assumption or some sort of a partial impact that you've modeled in.

我只是想確認你沒有在你的模型中假設，對全年產生全面影響，但是有某種部分年份的假設或某種你已經建模的部分影響。

Thanks, Ronny.

謝謝，羅尼。

We'll go to Dan and then Josh.

我們先去找丹，然後找喬希。

Yes.

是的。

Thanks, Ronny.

謝謝，羅尼。

It's a really good question that you're asking, which is how strong is the biomarker evidence here?

這是一個非常好的問題，您要問的問題是，這裡的生物標誌物證據有多強？

And how can that be used to support regulatory decisions?

以及如何將其用於支持監管決策？

I certainly think that's the direction the field is going.

我當然認為這是該領域的發展方向。

So in other words, when I look across all of the trials that have read out, again, this is the first plaque-removing antibody that has had a positive study, that hit its primary endpoint on the prespecified statistical analysis.

因此，換句話說，當我查看所有已讀出的試驗時，再次，這是第一個具有陽性研究的去斑塊抗體，在預先指定的統計分析中達到了其主要終點。

But even the other ones that didn't do that, when you look across the totality of evidence, you get a sense that there's a correlation between plaque removal in general and better cognitive performance.

但即使是其他沒有這樣做的人，當您查看全部證據時，您會感覺到總體上的斑塊去除與更好的認知表現之間存在相關性。

Here, we have probably the most significant plaque removal, the fastest, deepest plaque removal, and a very meaningful clinical effect.

在這裡，我們可能有最顯著的斑塊去除，最快、最深的斑塊去除，以及非常有意義的臨床效果。

So it's another point in this sort of dose response curve, comparing amyloid plaque removal and cognitive changes across different trials.

所以這是這種劑量反應曲線中的另一個點，比較不同試驗中澱粉樣斑塊的去除和認知變化。

As that gets filled out further and further by additional experiments, I think amyloid plaque removal could someday become an important surrogate that could aid in the regulatory approval of drugs.

隨著進一步的實驗進一步完善這一點，我認為澱粉樣斑塊去除有朝一日可能成為有助於藥物監管批准的重要替代物。

Are we there today?

我們今天在嗎？

I don't know.

我不知道。

That's a question for regulators and for the field and something that we certainly have believed in for many years and will continue to take up.

這是監管機構和該領域的問題，也是我們多年來一直相信的問題，並將繼續採取行動。

Thanks, Dan.

謝謝，丹。

Josh?

喬什？

Thanks, Ronny.

謝謝，羅尼。

As I mentioned earlier, we've guided to a 2- to 3-point price benefit in 2021 as a function of the 340B changes that we've made.

正如我之前提到的，作為我們所做的 340B 更改的函數，我們已將 2021 年的價格收益引導至 2 到 3 個百分點。

We've been very clear on 340B that the reason for the change is that we're providing discounts that patients don't get.

我們對 340B 非常清楚，改變的原因是我們提供了患者無法獲得的折扣。

And we want -- the program needs to be reformed and cleaned up.

我們希望 - 該計劃需要進行改革和清理。

So our assumption is, in 2021, there will be changes.

所以我們的假設是，在 2021 年，會有變化。

Whether -- and as I mentioned earlier, we also have mechanisms for contract pharmacies to get the discounts.

是否 - 正如我之前提到的，我們也有合同藥房獲得折扣的機制。

We want to ensure that patients on insulin can get the pass-through discount.

我們希望確保使用胰島素的患者可以獲得直通折扣。

So we're assuming in our 2021 guidance that -- not a full financial benefit for the full year, that there will be changes and modifications through the year, either as we try to work to ensure patients get the benefits of the discounts or if there are some administrative or legislative changes.

因此，我們在 2021 年的指導中假設——不是全年的全部經濟利益，全年都會有變化和修改，無論是我們努力確保患者獲得折扣的好處，還是如果有一些行政或立法變化。

Our next question comes from the line of Vamil Divan with Mizuho Securities.

我們的下一個問題來自瑞穗證券的 Vamil Divan。

So I also have a couple on the Alzheimer's theme.

所以我也有一些關於阿爾茨海默氏症的主題。

So one, just on the second Alzheimer's, TRAILBLAZER 2, an issue we've seen with other CNS drugs, maybe not as much in Alzheimer's.

所以一個，就在第二個阿爾茨海默病，TRAILBLAZER 2，我們在其他中樞神經系統藥物中看到的一個問題，在阿爾茨海默病中可能沒有那麼多。

But say you get these positive results, everyone gets excited.

但是說你得到了這些積極的結果，每個人都會很興奮。

But then the second trial, you might have to manage more of the placebo response or improperly getting patients into the trial.

但是在第二次試驗中，您可能需要管理更多的安慰劑反應或不恰當地讓患者參與試驗。

So I'm just wondering if there's anything you're doing differently or more carefully to make sure, for the second trial, you don't have patients who may be getting to the trial that otherwise shouldn't have.

因此，我只是想知道您是否採取了不同的措施或更仔細地確保在第二次試驗中，您沒有可能參加本不應該參加的試驗的患者。

Or you could say being to manage the placebo response, especially when the endpoint is this sort of clinical rating scale like a CDR Sum of the Boxes.

或者你可以說是要管理安慰劑反應，特別是當終點是這種臨床評級量表時，比如 CDR Sum of the Boxes。

And then my second questions are unrelated, but I guess partially related to Phase I. You mentioned that tau morphomer.

然後我的第二個問題是無關的，但我想部分與第一階段有關。你提到了 tau morphomer。

Why did you terminate it?

你為什麼終止它？

I'm just wondering if you can share any details behind that decision.

我只是想知道您是否可以分享該決定背後的任何細節。

Thanks, Vamil.

謝謝，瓦米爾。

We'll go to Dan for both of those.

我們會去丹為這兩個。

Yes.

是的。

Thanks, Vamil.

謝謝，瓦米爾。

It's a good point you raise.

你提出的觀點很好。

Of course, the placebo effect getting stronger in second trials is something that's been seen a lot in psychiatry and sometimes in pain studies.

當然，在第二次試驗中安慰劑效應越來越強，這在精神病學中已經很多，有時在疼痛研究中也經常出現。

As you pointed out, I'm not sure it's such a strong effect in Alzheimer's disease.

正如你所指出的，我不確定它對阿爾茨海默病有如此強烈的影響。

One thing that encourages us here and I think would allow us to see a strong signal even if there is some of that here, is -- well, maybe 2 things that encourage us.

在這裡鼓勵我們的一件事，我認為即使這裡有一些信號，也可以讓我們看到一個強烈的信號，那就是——好吧，也許有兩件事鼓勵我們。

First is the magnitude of the effect that we're seeing overall, which, as I said, hit stat-sig even in the small trial, and TRAILBLAZER 2 is much bigger.

首先是我們看到的整體效果的幅度，正如我所說，即使在小型試驗中也能達到 stat-sig，而 TRAILBLAZER 2 則要大得多。

Second is the consistency across endpoints and time points and statistical methods.

其次是端點和時間點和統計方法的一致性。

That gives us additional confidence as well.

這也給了我們額外的信心。

With respect to the -- your second question, which was the tau morphomer.

關於 - 你的第二個問題，即 tau morphomer。

For the Alzheimer's program here with AC Immune, we decided to pursue other promising tau morphomer candidates from AC Immune's research platform.

對於 AC Immune 的阿爾茨海默氏症項目，我們決定從 AC Immune 的研究平台尋找其他有前途的 tau 形態異構體候選物。

And therefore, we terminated this Phase I molecule.

因此，我們終止了這個 I 期分子。

That's probably all we'd say right now.

這可能就是我們現在要說的。

Our next question comes from the line of Carter Gould with Barclays.

我們的下一個問題來自於 Barclays 的 Carter Gould。

Congrats on the progress.

祝賀進展。

Dan, I guess I'd keep up the trend of Alzheimer's first.

丹，我想我會先跟上老年癡呆症的趨勢。

I guess just can you talk first around your longer-term view towards combination approaches with donanemab, particularly with an anti-tau inhibitor?

我想你能先談談你對與多納奈馬聯合治療的長期看法，特別是與抗 tau 抑製劑聯合治療嗎？

And then you had good momentum across the pain portfolio in the quarter and you've got a number of Phase II studies reading out with your epiregulin antibody.

然後，您在本季度的疼痛投資組合中勢頭良好，並且您的上皮調節蛋白抗體進行了多項 II 期研究。

Any color there on your level of confidence?

你的信心水平有什麼顏色嗎？

And if those data represent the key inputs regarding a get-go/no-go decision to Phase III, or will you need additional Phase II work, longer safety data?

如果這些數據代表了關於進入第三階段的決定的關鍵輸入，或者您是否需要額外的第二階段工作，更長的安全數據？

And any commentary on how you see that coexisting with tanezumab if that's approved?

如果獲得批准，您如何看待與 tanezumab 共存的任何評論？

Thanks, Carter.

謝謝，卡特。

Dan?

擔？

Great, Carter, 2 good and interesting questions.

太好了，卡特，2 個很好且有趣的問題。

So on combination of purchase for Alzheimer's.

所以對老年癡呆症的購買組合。

I do think that's what the future holds.

我確實認為這就是未來的發展方向。

One of the really neat things about donanemab is that we just treat until amyloid plaques are removed.

關於 donanemab 真正巧妙的事情之一是我們只治療直到澱粉樣斑塊被去除。

This is not a drug that we anticipate patients will be taking for the rest of their lives.

這不是我們預計患者將終生服用的藥物。

Once they're clear of amyloid plaques, we stopped treatment with this drug.

一旦他們清除了澱粉樣斑塊，我們就停止了這種藥物的治療。

We know from prior data that plaques don't come back.

我們從先前的數據中知道斑塊不會回來。

So you can imagine clearing a patient of amyloid plaques and then treating them with another mechanism that could be complementary.

因此，您可以想像清除患者的澱粉樣斑塊，然後用另一種可能互補的機制對其進行治療。

For example, an anti-tau drug or an immunomodulatory drug for Alzheimer's disease.

例如，抗 tau 藥物或治療阿爾茨海默病的免疫調節藥物。

So that's certainly something that we're considering and quite likely we'll pursue in the future.

所以這肯定是我們正在考慮的事情，而且很可能我們將來會追求。

Thanks for noting momentum in the pain space.

感謝您注意到疼痛領域的勢頭。

This is an area that is just so underserved by the pharmaceutical industry.

這是一個製藥行業服務不足的領域。

I think there's a variety of reasons, including regulatory thresholds, that have held back investment in an area that represents one of the greatest unmet medical needs.

我認為有多種原因，包括監管門檻，阻礙了對代表最大未滿足醫療需求之一的領域的投資。

This is why patients -- #1 reason why patients see doctors because they're in pain.

這就是為什麼患者——患者因為疼痛而去看醫生的#1原因。

And we know the drawbacks to current therapies.

我們知道當前療法的缺點。

So we designed a platform pain study which actually tests -- can test multiple molecules against multiple indications.

所以我們設計了一個平台疼痛研究來實際測試——可以針對多種適應症測試多種分子。

And we can keep funneling molecules in and get results out.

我們可以不斷地將分子匯集起來並得到結果。

Depending on the strength of the efficacy here, that will inform next steps, but we're confident that this study is well designed to show us whether we have meaningful treatment effects or not.

根據此處療效的強度，這將為下一步提供信息，但我們相信這項研究設計得很好，可以向我們展示我們是否有有意義的治療效果。

Of course, a holdback in pain, as I said before, is the regulatory bar which is heavily weighted towards safety.

當然，正如我之前所說，痛苦的抑制是高度重視安全的監管欄。

And typically, that takes a large number of patients to discharge.

通常，這需要大量患者出院。

Certainly, tanezumab, a perfect example of that with so many patients studied and a well-understood signal here on both efficacy and potential safety that needs to be resolved for the FDA.

當然，tanezumab 是一個完美的例子，研究瞭如此多的患者，並且在療效和潛在安全性方面都得到了很好的理解，FDA 需要解決這些問題。

And so the next question comes from Kerry Holford with Berenberg.

因此，下一個問題來自 Kerry Holford 和 Berenberg。

Just a couple left from me, please.

我只剩下一對了，拜託。

Firstly, on Prevail.

首先，關於盛行。

I wonder if you can talk a little more about this decision to acquire here.

我想知道你是否可以在這裡多談談這個收購的決定。

What attracted you to this particular gene therapy platform versus others?

這個特定的基因治療平台與其他平台相比，是什麼吸引了您？

And when might we see the data readout for the lead assets?

我們什麼時候可以看到領先資產的數據讀數？

And indeed, when might we see these potentially come to market?

事實上，我們什麼時候才能看到這些可能進入市場？

And then my second question is just more housekeeping in nature.

然後我的第二個問題是本質上更多的家務。

You talked about a stocking benefit in Q4.

您談到了第四季度的庫存收益。

I think it was $120 million.

我認為是 1.2 億美元。

Could you detail which drugs that impacted primarily and whether you'd expect an unwind into the next quarter?

您能否詳細說明主要影響哪些藥物以及您是否希望在下一季度放鬆？

Thanks, Kerry.

謝謝，克里。

We'll go to Dan for the question on the Prevail acquisition and then Josh on the stocking question.

我們將向 Dan 詢問有關 Prevail 收購的問題，然後向 Josh 詢問有關庫存問題的問題。

Yes.

是的。

Thanks, Kerry.

謝謝，克里。

We're really excited to have Prevail join Lilly.

我們很高興 Prevail 加入禮來公司。

This is a really great gene therapy platform.

這是一個非常棒的基因治療平台。

Why we picked -- and a great team.

我們為什麼選擇 - 以及一支偉大的團隊。

Those are clearly 2 of the reasons why we picked Prevail.

這顯然是我們選擇 Prevail 的兩個原因。

Also, I think there's just a natural synergy with the work we do at Lilly.

此外，我認為這與我們在禮來公司所做的工作有著自然的協同作用。

We're extremely strong in neuroscience, we have a deep commitment to the space.

我們在神經科學方面非常強大，我們對這個領域有著堅定的承諾。

And therefore, as we thought about what's our entry point into gene therapy, and we believe gene therapy will be an important treatment modality across therapeutic areas in the future, it made sense to enter gene therapy, to begin our efforts here in neuroscience.

因此，當我們思考基因治療的切入點是什麼，並且我們相信基因治療將成為未來治療領域的重要治療方式時，進入基因治療是有意義的，開始我們在神經科學領域的努力。

Prevail has got 2 exciting programs in the clinic already.

Prevail 在診所已經有 2 個令人興奮的項目。

One is for Parkinson's disease with GBA1 mutations, and it's a GBA1 gene transfer.

一種是針對具有 GBA1 突變的帕金森病，它是一種 GBA1 基因轉移。

There's a lot of face validity to that kind of approach, and we're looking forward to seeing data from that.

這種方法有很多表面有效性，我們期待從中看到數據。

The other similarly well-validated target here in frontotemporal dementia with GRN mutations.

另一個同樣得到充分驗證的目標是具有 GRN 突變的額顳葉癡呆。

And that's also, I think, exciting.

我認為這也是令人興奮的。

In terms of time lines to market, I think it's -- these programs are still very early.

就上市時間而言，我認為這些計劃還很早。

We're just in the first few patients here, and we'll have to see what the data show to inform those time lines.

我們只是這裡的前幾名患者，我們必須看看數據顯示什麼來告知這些時間線。

Thanks, Dan.

謝謝，丹。

Josh?

喬什？

Thanks, Kerry.

謝謝，克里。

Yes.

是的。

On inventory, what we've said is if you look at Q4 2020 inventory in the U.S., inventory levels versus Q4 of 2019, we're $120 million higher.

在庫存方面，我們所說的是，如果您查看美國 2020 年第四季度的庫存，與 2019 年第四季度相比，庫存水平高出 1.2 億美元。

We're not concerned about that.

我們對此並不擔心。

2019 was an unusually low year when you just look at days of stock.

僅查看庫存天數，2019 年是異常低迷的一年。

So the $120 million is in line with our expectations.

所以1.2億美元符合我們的預期。

But now as we look into Q1 2021, we do expect that $120 million will burn off.

但現在我們展望 2021 年第一季度，我們確實預計 1.2 億美元將被燒掉。

And it's across the portfolio.

它遍布整個投資組合。

But as you would imagine, Trulicity is one of the products.

但正如您想像的那樣，Trulicity 是其中一種產品。

We see a little bit extra in Taltz, and I think some of this is a function of the anticipation of increased volume for Taltz as a function of the ESI win that will go in -- that went into effect on January 1. And we also see some on Alimta.

我們在 Taltz 中看到了一些額外的東西，我認為其中一些是由於預期 Taltz 的銷量會隨著 ESI 獲勝而增加——這將在 1 月 1 日生效。我們還在 Alimta 上看到一些。

We did see some purchasing patterns through the year in oncology, I think some of which was related to the pandemic and some delays in infused products.

全年我們確實在腫瘤學領域看到了一些購買模式，我認為其中一些與大流行和輸液產品的一些延遲有關。

But those are probably the 3 biggest products where we see this on.

但這些可能是我們看到的 3 大產品。

So we would expect that $120 million to burn off in Q1 as it normally does.

因此，我們預計第一季度將像往常一樣燒掉 1.2 億美元。

The other piece, though, that we want to make investors aware is, remember last year in Q1, we saw a $250 million build in inventory on a worldwide basis.

不過，我們想讓投資者意識到的另一件事是，請記住去年第一季度，我們在全球範圍內看到了 2.5 億美元的庫存。

This was as customers were stocking up in anticipation of the lockdowns that were coming with the pandemic.

這是因為客戶正在囤積庫存，以期待隨著大流行而出現的封鎖。

So I think if you put those 2 things together, the $250 million build last year and what we assumed to be $120 million burn this year, that's about $370 million of headwind when you just do year-over-year compare in growth.

所以我認為，如果你把這兩件事放在一起，去年 2.5 億美元的建設和我們假設今年燒掉的 1.2 億美元，當你只進行同比增長比較時，這大約是 3.7 億美元的逆風。

And that's -- could be up to like 6 points or something.

那就是——可能高達 6 分之類的。

Again, it's not a concern.

同樣，這不是一個問題。

It's built into how we think about the year.

它已融入我們對這一年的看法。

But we do want to remind investors on that piece.

但我們確實想就此提醒投資者。

Now -- and I think throughout the year, we're going to have some strange compares.

現在 - 我認為全年，我們都會進行一些奇怪的比較。

Remember that we sold $871 million in bamlanivimab in Q4.

請記住，我們在第四季度出售了 8.71 億美元的 bamlanivimab。

We expect to have significant sales this year as well.

我們預計今年也有可觀的銷售額。

So we'll tease all that out as we go through.

因此，我們將在進行過程中梳理出所有這些內容。

But on the underlying base business, you should expect to see an inventory negative growth effect in Q1.

但在基礎業務方面，您應該會在第一季度看到庫存負增長效應。

And we'll go to Dave now for the close.

我們現在去戴夫那裡結束。

Great.

偉大的。

Thanks, Kevin, and to the team.

謝謝，凱文，感謝團隊。

We appreciate everyone's participation in today's call, and of course, your interest in Eli Lilly.

我們感謝大家參加今天的電話會議，當然也感謝您對禮來公司的興趣。

2020 was a strong year for the company, and we anticipate an important year in 2021.

2020 年對公司來說是強勁的一年，我們預計 2021 年將是重要的一年。

A lot of questions related to Alzheimer's today.

今天有很多與阿爾茨海默氏症有關的問題。

We're excited about that as well.

我們也對此感到興奮。

But just a reminder, we have upcoming readouts for tirzepatide with [SURPASS] (corrected by the company after the call) 2, 3 and 5 over the coming weeks and months; as well as a number of readouts this year in our immunology portfolio for baricitinib, lebrikizumab and mirikizumab in important indications.

但提醒一下，在接下來的幾周和幾個月內，我們將通過 [SURPASS]（由公司在電話會議後更正）2、3 和 5 進行 tirzepatide 的讀數；以及今年我們在重要適應症中對巴瑞克替尼、lebrikizumab 和 mirikizumab 的免疫學產品組合中的一些讀數。

The company has a broad and diversified set of opportunities ahead for additional innovation for patients.

該公司在為患者提供更多創新方面擁有廣泛而多樣化的機會。

With our strong lineup of marketed products as well and this industry-leading pipeline, we believe we continue to be a compelling investment.

憑藉我們強大的上市產品陣容和行業領先的管道，我們相信我們將繼續成為一項引人注目的投資。

So thanks for dialing in.

所以感謝您撥入。

Please follow-up with the IR team if you have any additional questions.

如果您有任何其他問題，請與 IR 團隊聯繫。

And hope everyone has a great day and a great weekend.

並希望每個人都有一個美好的一天和一個美好的周末。

Take care.

小心。

Thank you.

謝謝你。

Ladies and gentlemen, that does conclude our conference for today.

女士們先生們，今天的會議到此結束。

We thank you for your participation and for using AT&T conferencing service.

我們感謝您的參與和使用 AT&T 會議服務。

You may now disconnect.

您現在可以斷開連接。