禮來公司 (LLY) 2021 Q4 法說會逐字稿

Ladies and gentlemen, thank you for standing by, and welcome to the Lilly Q4 2021 Earnings Call. (Operator Instructions) As a reminder, today's conference is being recorded.

女士們，先生們，感謝您的支持，歡迎參加禮來公司 2021 年第四季度財報電話會議。 （操作員說明）提醒一下，今天的會議正在錄製中。

I would now like to turn the conference over to Vice President of Investor Relations, Kevin Hern. Please go ahead.

我現在想將會議轉交給投資者關係副總裁 Kevin Hern。請繼續。

Good morning. Thank you for joining us for Eli Lilly and Company's Q4 2021 Earnings Call. I'm Kevin Hern, Vice President of Investor Relations. And joining me on today's call are Dave Ricks, Lilly's Chair and CEO; Anat Ashkenazi, Chief Financial Officer; Dr. Dan Skovronsky, Chief Scientific and Medical Officer; Anne White, President of Lilly Neuroscience; Ilya Yuffa, President of Lilly International; Jake Van Naarden, CEO of Loxo Oncology at Lilly and President of Lilly Oncology; Mike Mason, President of Lilly Diabetes; and Patrik Jonsson, President of Lilly Immunology and Lilly USA. We're also joined by Lauren Zierke, Kento Ueha and Sara Smith of the Investor Relations team.

早上好。感謝您參加禮來公司 2021 年第四季度財報電話會議。我是投資者關係副總裁 Kevin Hern。和我一起參加今天電話會議的還有禮來公司的董事長兼首席執行官戴夫·里克斯（Dave Ricks）； Anat Ashkenazi，首席財務官； Dan Skovronsky 博士，首席科學和醫學官；禮來公司神經科學總裁 Anne White；禮來國際總裁 Ilya Yuffa； Jake Van Naarden，禮來公司 Loxo 腫瘤學首席執行官兼禮來腫瘤學總裁；禮來糖尿病總裁 Mike Mason；以及禮來免疫學和禮來美國公司總裁 Patrik Jonsson。投資者關係團隊的 Lauren Zierke、Kento Ueha 和 Sara Smith 也加入了我們的行列。

During this conference call, we anticipate making projections and forward-looking statements based on our current expectations. Our actual results could differ materially due to a number of factors, including those listed on Slide 3. Additional information concerning factors that could cause actual results to differ materially is contained in our latest Form 10-K and subsequent Forms 10-Q and 8-K filed with the Securities and Exchange Commission.

在這次電話會議期間，我們預計會根據我們目前的預期做出預測和前瞻性陳述。由於多種因素，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產生重大差異的因素的其他信息包含在我們最新的 10-K 表格和後續 10-Q 和 8- 表格中K 向證券交易委員會提交了申請。

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

我們提供的有關我們的產品和管道的信息是為了投資界的利益。它不是為了促銷，也不足以做出處方決定。當我們過渡到我們準備好的評論時，請注意我們的評論將集中在非公認會計準則財務指標上。

Now I'll turn the call over to Dave.

現在我將把電話轉給戴夫。

Thanks, Kevin. 2021 was another outstanding year for Lilly as we delivered strong top and bottom line growth and positive pivotal readouts for 5 important assets with the potential to launch in the next 2 years. As we move into 2022, we continue to build on this foundation and are determined to deliver on our long-term outlook to drive top-tier revenue growth, expand operating margins and innovate to develop and launch new medicines for patients that address significant unmet needs.

謝謝，凱文。 2021 年對禮來（Lilly）來說又是傑出的一年，因為我們實現了強勁的營收和利潤增長，以及 5 項有可能在未來 2 年內推出的重要資產的關鍵數據。隨著我們進入 2022 年，我們將繼續在此基礎上再接再厲，並決心實現我們的長期前景，以推動頂級收入增長、擴大營業利潤率並進行創新，為患者開發和推出新藥，以解決重大未滿足的需求.

Unpacking our 2021 performance on Slide 4. You can see the progress we've made on our strategic deliverables. Q4 revenue [growth] was 8% and was driven by volume growth of 11% while when excluding revenue from COVID-19 antibodies, revenue grew 6% for the quarter and 10% for the full year. This volume-driven performance is attributable to our key growth products, which grew by 28% and now account for 61% of our core business in Q4.

在幻燈片 4 上解開我們 2021 年的表現。您可以看到我們在戰略可交付成果方面取得的進展。第四季度收入 [增長] 為 8%，受銷量增長 11% 的推動，而排除 COVID-19 抗體收入時，本季度收入增長 6%，全年增長 10%。這種以銷量為導向的業績歸功於我們的主要增長產品，該產品增長了 28%，現在占我們第四季度核心業務的 61%。

On our non-GAAP, gross margin was 76.1% in Q4, a decrease of approximately 250 basis points, driven by increased sales of COVID-19 antibodies, which have a lower gross margin profile. Our non-GAAP operating margin was 31.7%, representing a decrease of approximately 130 basis points as a result of the lower gross margin percent just mentioned. For pipeline milestones, we have shared several important updates since our Q3 earnings call, including additional positive Phase III readouts for mirikizumab in ulcerative colitis and lebrikizumab in atopic dermatitis, the initiation of a rolling submission in the U.S. for pirtobrutinib in mantle cell lymphoma and our submission of bebtelovimab to the FDA for emergency use authorization for the treatment of mild to moderate COVID-19.

根據我們的非公認會計原則，第四季度的毛利率為 76.1%，下降了約 250 個基點，這是由於毛利率較低的 COVID-19 抗體銷量增加所致。我們的非美國通用會計準則營業利潤率為 31.7%，由於剛才提到的較低毛利率百分比，下降了約 130 個基點。對於管道里程碑，我們已經分享了自第三季度財報電話會議以來的幾項重要更新，包括針對潰瘍性結腸炎的 mirikizumab 和針對特應性皮炎的 lebrikizumab 的更多積極 III 期讀數，在美國啟動了針對套細胞淋巴瘤的 pirtobrutinib 的滾動提交以及我們的向 FDA 提交 bebtelovimab 用於治療輕度至中度 COVID-19的緊急使用授權。

We also continue to put our cash flow to work to create long-term value and recently announced our plans to make significant investments in new manufacturing sites in both North Carolina and Ireland. These investments will bolster the resilience and capacity of our supply chain as we launch new products to drive meaningful long-term growth. In addition, this quarter, we announced strategic research collaborations with a focus on new modalities as we continue to augment internal discovery capabilities.

我們還繼續將我們的現金流用於創造長期價值，並且最近宣布我們計劃對北卡羅來納州和愛爾蘭的新製造基地進行重大投資。隨著我們推出新產品以推動有意義的長期增長，這些投資將增強我們供應鏈的彈性和能力。此外，本季度，隨著我們繼續增強內部發現能力，我們宣布了以新模式為重點的戰略研究合作。

Finally, on financials, we announced a 15% increase to the dividend for the fourth consecutive year. And in Q4, we distributed nearly $800 million to shareholders via the dividend and completed another $750 million in share repurchases.

最後，在財務方面，我們宣布連續第四年將股息提高 15%。在第四季度，我們通過股息向股東分配了近 8 億美元，並完成了另外 7.5 億美元的股票回購。

Moving to Slides 5 and 6. You'll see a list of key events since our Q3 earnings call, including several important regulatory, clinical, business development and COVID-19 therapy updates we are discussing today or that were part of the discussion during our December 15 investment community meeting.

轉到幻燈片 5 和 6。您將看到自我們第三季度財報電話會議以來的關鍵事件列表，包括我們今天討論的幾項重要的監管、臨床、業務發展和 COVID-19 治療更新，或者是我們在我們的討論中的一部分12 月 15 日投資界會議。

So now I'll turn the call over to Anat to review our Q4 and full year 2021 results.

因此，現在我將把電話轉給 Anat，以審查我們的第四季度和 2021 年全年業績。

Thanks, Dave. Slides 7 and 8 summarize financial performance in the fourth quarter and full year 2021. I'll focus my comments on non-GAAP performance.

謝謝，戴夫。幻燈片 7 和 8 總結了 2021 年第四季度和全年的財務業績。我將把我的評論集中在非 GAAP 業績上。

In Q4, revenue grew 8% and revenue excluding COVID-19 antibodies increased 6%, highlighting solid momentum for our core business. Full year revenue growth was 10% on that latter basis. Gross margin as a percent of revenue declined 250 basis points to 76.1% in Q4. The decrease in gross margin percent was driven by higher sales of COVID-19 antibodies with shipments this quarter of bamlanivimab and etesevimab also having lower gross margin profile compared to bamlanivimab sales in the base period.

第四季度，收入增長 8%，不包括 COVID-19 抗體的收入增長 6%，突顯了我們核心業務的強勁勢頭。在後者的基礎上，全年收入增長為 10%。第四季度毛利率佔收入的百分比下降 250 個基點至 76.1%。毛利率下降的原因是 COVID-19抗體的銷售額增加，本季度 bamlanivimab 和 etesevimab 的出貨量也低於基期 bamlanivimab 的銷售額。

Total operating expenses grew 5% this quarter. Marketing, selling and administrative expenses increased 2% while R&D expenses increased 7%, driven by higher development expenses for late-stage pipeline opportunities, including donanemab, pirtobrutinib and tirzepatide, which were partially offset by lower development expenses for COVID-19 therapies. We invested approximately $40 million in research and development for COVID-19 therapies in Q4, bringing our total COVID-19 R&D investment to approximately $400 million for the full year.

本季度總運營費用增長了 5%。營銷、銷售和管理費用增長 2%，而研發費用增長 7%，這是由於後期管道機會的開發費用增加，包括多納奈馬、pirtobrutinib 和 tirzepatide，這部分被 COVID-19療法的開發費用降低所抵消。我們在第四季度投資了約 4000 萬美元用於 COVID-19 療法的研發，使我們全年 COVID-19 研發投資總額達到約 4 億美元。

Operating income increased 3% compared to Q4 2020, and operating income as a percent of revenue was 31.7% for the quarter, a decrease of 130 basis points. This decrease was driven by lower gross margin percent partially offset by lower marketing, selling and administrative expenses as a percent of revenue. Full year operating margin was 29.9%, in line with our expectations.

與 2020 年第四季度相比，營業收入增長了 3%，本季度營業收入佔收入的百分比為 31.7%，下降了 130 個基點。這一下降是由於較低的毛利率百分比被較低的營銷、銷售和管理費用佔收入的百分比所部分抵消。全年營業利潤率為 29.9%，符合我們的預期。

Other income and expense was an expense of approximately $7 million this quarter compared to an expense of $31 million in Q4 2020. Our Q4 effective tax rate was 10.3%, a decrease of 280 basis points driven primarily by net discrete tax benefits. At the bottom line, we delivered solid growth as earnings per share increased 8% in Q4 and 20% for the full year.

本季度其他收入和支出約為 700 萬美元，而 2020 年第四季度的支出為 3100 萬美元。我們第四季度的有效稅率為 10.3%，主要受淨離散稅收優惠的推動，下降了 280 個基點。在底線，我們實現了穩健的增長，因為第四季度每股收益增長了 8%，全年增長了 20%。

On Slide 9, we quantify the effect of price, rate and volume on revenue growth, and we continue to be encouraged by the growth seen across key geographies. This quarter, U.S. revenue grew 13%. Excluding revenue from COVID-19 antibodies, revenue grew 11% in the U.S. This growth driven by volume was led by Trulicity, Taltz, Jardiance, Verzenio and Olumiant. The net price decline of 2% in the U.S. this quarter was driven by lower realized prices for insulins, primarily due to changes to estimates for rebates and discounts. For the full year, our U.S. net price decrease of 1% was in line with our expectations.

在幻燈片 9 上，我們量化了價格、費率和數量對收入增長的影響，我們繼續對主要地區的增長感到鼓舞。本季度，美國收入增長了 13%。不包括 COVID-19 抗體的收入，美國的收入增長了 11%。這一增長由 Trulicity、Taltz、Jardiance、Verzenio 和 Olumiant 引領。本季度美國淨價格下降 2% 的原因是胰島素的實際價格下降，這主要是由於對回扣和折扣的估計發生了變化。全年，我們的美國淨價格下降 1% 符合我們的預期。

Moving to Europe, revenue in Q4 declined 3% in constant currency. Excluding the impact of the loss of exclusivity for Alimta, revenue grew 11% in constant currency, driven primarily by volume growth for Trulicity, Olumiant, Taltz and Verzenio. We are encouraged with the momentum of our business in Europe and expect continued growth excluding Alimta.

移至歐洲，第四季度的收入按固定匯率計算下降了 3%。排除失去 Alimta 獨家經營權的影響，按固定匯率計算，收入增長了 11%，主要受 Trulicity、Olumiant、Taltz 和 Verzenio 銷量增長的推動。我們對我們在歐洲的業務發展勢頭感到鼓舞，並預計不包括 Alimta 將繼續增長。

In Japan, revenue in Q4 decreased 14% in constant currency. Revenue in Japan continues to be negatively impacted by decreased demand for several products that have lost market exclusivity, including Cymbalta and Alimta as well as by the COVID pandemic. With key growth products now representing 56% of total Japan revenue, we expect to return to growth beginning in 2023.

在日本，按固定匯率計算，第四季度的收入下降了 14%。日本的收入繼續受到對幾種失去市場排他性的產品需求下降的負面影響，包括 Cymbalta 和 Alimta 以及 COVID 大流行。由於關鍵增長產品現在佔日本總收入的 56%，我們預計將從 2023 年開始恢復增長。

In China, revenue grew 13% in constant currency, primarily driven by volume from our continued uptake of Tyvyt and Trulicity as well as the timing of supply for Cialis to the third-party selling the product. Q4 revenue growth was negatively affected by the updated 2022 NRDL price reductions on inventory already in the channel especially for Tyvyt. In 2022, we expect the NRDL price reduction headwind to largely offset volume growth in Q1, but we also expect volume growth to accelerate throughout the year and exceed the impact of these price reductions. Moving forward, we're excited about the significant growth we're seeing in China, over 40% in constant currency in 2021, with improved access expected to continue to drive future growth.

在中國，按固定匯率計算，收入增長了 13%，主要是由於我們繼續採用 Tyvyt 和 Trulicity 的銷量，以及向銷售該產品的第三方供應 Cialis 的時機。第四季度收入增長受到 2022 年國家醫保目錄更新後的渠道庫存降價的負面影響，尤其是 Tyvyt。 2022 年，我們預計 NRDL 降價逆風將在很大程度上抵消第一季度的銷量增長，但我們也預計全年銷量增長將加速並超過這些降價的影響。展望未來，我們對我們在中國看到的顯著增長感到興奮，2021 年按固定匯率計算，增長超過 40%，預計獲得改善將繼續推動未來增長。

Revenue in the rest of the world increased 16% in constant currency this quarter, driven primarily by sales of neuro medicine.

本季度全球其他地區的收入按固定匯率計算增長了 16%，主要受神經藥物銷售的推動。

We continue to expect a mid-single-digit net price decline in 2022 for the U.S., Europe and Japan. In China, the expanded NRDL access for our products should lead to significant volume increase but also high double-digit decline in price. As a result, we expect total company net price decline in the high single digit in 2022. At the bottom of the slide is the price, rate and volume effect on revenue for all 2021, which shows strong double-digit volume-driven revenue growth across most major geographies. As shown on Slide 10, our key growth products continue to drive robust worldwide volume growth. These products drove 14 percentage points of growth this quarter and continue to bolster our overall performance and outlook.

我們繼續預計 2022 年美國、歐洲和日本的淨價格將出現中個位數的下降。在中國，我們產品的 NRDL 准入範圍擴大應會導致銷量大幅增長，但價格也會出現兩位數的高位下跌。因此，我們預計 2022 年公司總淨價將出現高個位數下降。幻燈片底部是價格、費率和銷量對 2021 年所有收入的影響，顯示出強勁的兩位數銷量驅動的收入增長在大多數主要地區。如幻燈片 10 所示，我們的主要增長產品繼續推動全球銷量的強勁增長。這些產品在本季度推動了 14 個百分點的增長，並繼續支持我們的整體業績和前景。

Slide 11 further highlights the contribution of our key growth products. This quarter, these brands generated over $4.2 billion in revenue and made up 61% of our core business revenue. In Q4, these newer medicines grew by 28%, and Trulicity, Jardiance, Taltz and Verzenio all continued to outgrow their respective classes. We are particularly pleased with the continued market growth of both the GLP-1 and the SGLT2 classes where Trulicity and Jardiance are market leaders. We are also encouraged by the strong uptake of Verzenio we saw in Q4, driven by the approval and launch of the adjuvant indication, which has led to an inflection in both new and total prescriptions.

幻燈片 11 進一步突出了我們主要增長產品的貢獻。本季度，這些品牌創造了超過 42 億美元的收入，占我們核心業務收入的 61%。在第四季度，這些較新的藥物增長了 28%，而 Trulicity、Jardiance、Taltz 和 Verzenio 都繼續超過各自的類別。我們對 Trulicity 和 Jardiance 是市場領導者的 GLP-1 和 SGLT2 類的持續市場增長感到特別高興。我們也對我們在第四季度看到的 Verzenio 的強勁吸收感到鼓舞，這得益於輔助適應症的批准和推出，這導致了新處方和總處方的變化。

On Slide 12, we provide an update on capital allocation. In 2021, we invested $9.3 billion to drive our future growth through a combination of R&D expenditures, business development outlays and capital investments. In addition, we returned approximately $3.1 billion to shareholders in dividends and repurchased approximately $1.3 billion in stock. Our capital allocation priorities remain unchanged as we continue to fund our marketed products and expected launches, invest in our pipeline, evaluate opportunities for external innovation to augment our future growth prospects and return excess capital to shareholders.

在幻燈片 12 中，我們提供了資本配置的最新信息。 2021 年，我們投資了 93 億美元，通過研發支出、業務發展支出和資本投資相結合來推動我們的未來增長。此外，我們向股東返還了約 31 億美元的股息，並回購了約 13 億美元的股票。我們的資本配置優先事項保持不變，因為我們將繼續為我們的營銷產品和預期推出提供資金、投資我們的管道、評估外部創新機會以擴大我們未來的增長前景並將多餘的資本返還給股東。

On Slide 13 is our 2022 financial guidance we issued in December. As I shared then, the financial impact from the loss of exclusivity of Alimta in Europe and Japan will continue in the first half of 2022 while the impact from Alimta's U.S. patent expiry will start with the limited launch from a single generic company in Q1 before the full launch of additional generic entrants starting in Q2. We expect roughly $375 million of revenue from COVID-19 antibodies in Q1 from the shipment of the remaining doses attributable to last November's U.S. government purchase agreement. We continue to invest in our bright future, advancing promising R&D opportunities and preparing for exciting potential launches from our late-stage pipeline, which we believe will help drive top-tier revenue growth through at least 2030.

幻燈片 13 是我們在 12 月發布的 2022 年財務指導。正如我當時所分享的，失去 Alimta 在歐洲和日本的排他性所帶來的財務影響將在 2022 年上半年持續，而 Alimta 在美國的專利到期所帶來的影響將從第一季度單一仿製藥公司的有限推出開始。從第二季度開始全面推出其他仿製藥進入者。我們預計第一季度 COVID-19抗體的收入約為 3.75 億美元，來自去年 11 月美國政府採購協議的剩餘劑量的發貨。我們將繼續投資於我們光明的未來，推進有前景的研發機會，並為我們後期管道的激動人心的潛在發布做準備，我們相信這將有助於推動頂級收入增長至少到 2030 年。

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

現在，我將把電話轉給 Dan，以提供有關我們管道的更新。

Thank you, Anat. 2021 was a remarkable year for Lilly's pipeline. We delivered positive data on 5 molecules: tirzepatide, donanemab, pirtobrutinib, mirikizumab and lebrikizumab, all of which have the potential to launch in the next 2 years. And we're excited about the potential these molecules hold for patients. In addition, we launched and submitted several key new indications for in-market products, including important new indications for Verzenio and Jardiance. And also, we advanced our early-stage pipeline.

謝謝你，阿納特。 2021 年對於禮來（Lilly）的管道來說是非凡的一年。我們提供了 5 個分子的陽性數據：tirzepatide、donanemab、pirtobrutinib、mirikizumab 和 lebrikizumab，所有這些分子都有可能在未來 2 年內推出。我們對這些分子對患者的潛力感到興奮。此外，我們推出並提交了幾個在市產品的關鍵新適應症，包括 Verzenio 和 Jardiance 的重要新適應症。此外，我們推進了我們的早期管道。

Just a few weeks ago, we provided an extensive R&D update across our therapeutic areas and shared our excitement about the next wave of innovation coming from Lilly. As a result, today's R&D update will be brief and focus on the progress we've made since our last earnings call.

就在幾週前，我們在我們的治療領域提供了廣泛的研發更新，並分享了我們對來自禮來 (Lilly) 的下一波創新浪潮的興奮。因此，今天的研發更新將是簡短的，並將重點關注自上次財報電話會議以來我們取得的進展。

Slide 14 shows select pipeline opportunities as of January 31, and Slides 15 and 16 show a recap of 2021 key events and potential key events for 2022. In diabetes, with the recent submission in Japan, we've now submitted tirzepatide across all major geographies for the treatment of type 2 diabetes. We look forward to potential approvals for this important medicine this year. We anticipate U.S. regulatory action in type 2 diabetes as well as the top line readout from SURMOUNT-1, both by midyear. In Japan, we submitted Jardiance for heart failure with preserved ejection fraction and received approval for Jardiance for treatment of heart failure with reduced ejection fraction.

幻燈片 14 顯示了截至 1 月 31 日的選定管道機會，幻燈片 15 和 16 顯示了 2021 年關鍵事件和 2022 年潛在關鍵事件的回顧。在糖尿病方面，隨著最近在日本提交，我們現在已經在所有主要地區提交了 tirzepatide用於治療2型糖尿病。我們期待今年這種重要藥物的潛在批准。我們預計美國將在年中之前對 2 型糖尿病採取監管行動以及 SURMOUNT-1 的一線讀數。在日本，我們提交了 Jardiance 治療射血分數保留的心力衰竭，並獲得了 Jardiance 治療射血分數降低的心力衰竭的批准。

Moving to oncology. We shared encouraging updated data at ASH for pirtobrutinib for both chronic lymphocytic leukemia and mantle cell lymphoma. We continue to progress this molecule and initiated another Phase III study in first-line CLL comparing pirtobrutinib to chemoimmunotherapy. During our December meeting, we also announced the initiation of a rolling submission for pirtobrutinib for MCL in the U.S. We plan to complete this submission this year with anticipated regulatory action in early 2023, and we're excited to potentially bring this important medicine to patients on this accelerated timeline.

轉向腫瘤學。我們在 ASH 分享了關於 pirtobrutinib 治療慢性淋巴細胞白血病和套細胞淋巴瘤的令人鼓舞的最新數據。我們繼續推進該分子，並在一線 CLL 中啟動了另一項 III 期研究，將 pirtobrutinib 與化學免疫療法進行比較。在 12 月的會議上，我們還宣佈在美國開始滾動提交用於 MCL 的 pirtobrutinib。我們計劃在今年完成此提交，預計在 2023 年初採取監管行動，我們很高興有可能將這種重要藥物帶給患者在這個加速的時間線上。

For Verzenio, we received approval for high-risk early breast cancer in Japan for the cohort 1 population study to monarchE and are pleased that this approval represents 90% of the intent-to-treat population. We've also made the difficult decision to terminate further enrollment in the Phase III study of Verzenio for HR+/HER2+ early breast cancer in response to the changing treatment landscape and global enrollment challenges. Importantly, this decision does not change our commitment to and investment in breast cancer. In addition, we began a Phase III study for selpercatinib for the treatment of adjuvant RET-positive non-small cell lung cancer, and we also dosed the first patient in the U.S. trial of our BCL-2 inhibitor.

對於 Verzenio，我們在 monarchE 的隊列 1 人群研究中獲得了日本高危早期乳腺癌的批准，並且很高興該批准代表了 90% 的意向治療人群。為應對不斷變化的治療環境和全球註冊挑戰，我們還做出了艱難的決定，終止 Verzenio 用於 HR + / HER2 + 早期乳腺癌的 III 期研究的進一步註冊。重要的是，這一決定不會改變我們對乳腺癌的承諾和投資。此外，我們開始了一項針對 selpercatinib 治療輔助 RET 陽性非小細胞肺癌的 III 期研究，我們還為美國試驗中的第一位患者服用了我們的 BCL-2 抑製劑。

In immunology, we announced positive top line data for our Phase III maintenance study of mirikizumab in ulcerative colitis. We're pleased that the study met all primary and key secondary endpoints, and we look forward to submissions in the first half of this year. We also announced positive top line Phase III results for lebrikizumab in combination with topical corticosteroids, and we're encouraged that data to date has demonstrated a competitive profile for treatment of atopic dermatitis. We await maintenance data for lebrikizumab in the first half of this year in advance of global submissions which are expected by the end of 2022.

在免疫學方面，我們公佈了 mirikizumab 在潰瘍性結腸炎中的 III 期維持研究的陽性頂線數據。我們很高興該研究達到了所有主要和關鍵次要終點，我們期待在今年上半年提交。我們還宣布了 lebrikizumab 聯合外用皮質類固醇的積極頂線 III 期結果，我們感到鼓舞的是，迄今為止的數據已證明在治療特應性皮炎方面具有競爭力。我們等待今年上半年 lebrikizumab 的維護數據，然後再全球提交，預計到 2022 年底。

Moving to baricitinib. We announced last week that based on top line efficacy results from 2 Phase III trials, we've decided to discontinue the Phase III development program for lupus. For atopic dermatitis in the U.S., we're in ongoing discussions with the FDA but do not have alignment with the agency on the indicated population, which could possibly lead to a complete response letter. We expect regulatory action for this indication very soon. Finally, we have submitted baricitinib for alopecia areata in the U.S. and hope it will become the first medicine approved for patients living with this disease later this year. In our early phase immunology portfolio, we started a new Phase I study for a CD19 antibody and we've discontinued our oral IL-17 inhibitor.

轉向巴瑞替尼。我們上周宣布，根據 2 項 III 期試驗的一線療效結果，我們決定停止狼瘡的 III 期開發計劃。對於美國的特應性皮炎，我們正在與 FDA 進行討論，但在指定人群方面與 FDA 不一致，這可能會導致完整的回复信。我們預計很快就會針對這一跡象採取監管行動。最後，我們在美國提交了治療斑禿的巴瑞替尼，希望它成為今年晚些時候批准用於患有這種疾病的患者的第一個藥物。在我們的早期免疫學產品組合中，我們開始了一項針對 CD19 抗體的新 I 期研究，並且我們已經停止了我們的口服 IL-17 抑製劑。

Moving to neurodegeneration. In our early-phase pipeline, we announced that we've received Breakthrough Therapy Designation for N3pG4, an additional amyloid-lowering agent for which we intend to initiate pivotal trials by the end of this year. We have evidence that this therapy has completely and rapidly cleared amyloid plaque, and we're exploring flexible dosing regimens, including subcutaneous dosing. For the treatment of Alzheimer's disease, we also began a Phase II trial for our O-GlcNAcase inhibitor, an oral small molecule targeting tau. While donanemab has been a primary focus for investors, we're pleased with the continued clinical advancement of the rest of our neurodegeneration pipeline.

轉向神經變性。在我們的早期管道中，我們宣布我們已經獲得了 N3pG4 的突破性治療指定，這是一種額外的澱粉樣蛋白降低劑，我們打算在今年年底之前啟動關鍵試驗。我們有證據表明這種療法已經完全快速地清除了澱粉樣蛋白斑塊，我們正在探索靈活的給藥方案，包括皮下給藥。為了治療阿爾茨海默病，我們還開始了 O-GlcNAcase 抑製劑的 II 期試驗，O-GlcNAcase 抑製劑是一種靶向 tau 的口服小分子。雖然 donanemab 一直是投資者的主要關注點，但我們對我們其餘神經退行性疾病管道的持續臨床進展感到高興。

Now turning to donanemab. In December, we initiated 2 additional Phase III studies: TRAILBLAZER-ALZ 3, our prevention study for asymptomatic Alzheimer's disease; and TRAILBLAZER-ALZ 4, our head-to-head plaque clearance study compared to Aduhelm. It's been less than 1 year since we published the positive randomized controlled TRAILBLAZER-ALZ study, which demonstrated clinically meaningful benefits on endpoints of cognition and function. Since then, we have focused investors on the need for replication from our well-designed expanded Phase III study, TRAILBLAZER-ALZ 2, which is now fully enrolled and expected to read out in mid-2023. While a lot has happened in this space during this last year and more events are likely before we get top line results next year, what hasn't changed for us is the importance of the TRAILBLAZER-ALZ 2 readout and our confidence in both donanemab and the unique study design. Given the impact of this devastating disease, we believe that if TRAILBLAZER-ALZ 2 provides positive confirmatory data, we can't see a scenario where there's not global reimbursement, patient access and broad use of donanemab.

現在轉向donanemab。 12 月，我們啟動了另外 2 項 III 期研究： TRAILBLAZER-ALZ 3，我們針對無症狀阿爾茨海默病的預防研究；和 TRAILBLAZER-ALZ 4，我們與 Aduhelm 相比的頭對頭斑塊清除研究。自我們發表陽性隨機對照 TRAILBLAZER-ALZ 研究以來不到 1 年，該研究證明了在認知和功能終點方面具有臨床意義的益處。從那時起，我們將投資者的注意力集中在復制我們精心設計的擴展 III 期研究 TRAILBLAZER-ALZ 2 的需要上，該研究現已完全註冊，預計將於 2023 年年中公佈。雖然去年這個領域發生了很多事情，並且在我們明年獲得頂級結果之前可能會發生更多事件，但對我們來說沒有改變的是 TRAILBLAZER-ALZ 2 讀數的重要性以及我們對 donanemab 和獨特的學習設計。鑑於這種毀滅性疾病的影響，我們認為，如果 TRAILBLAZER-ALZ 2 提供了積極的確認數據，我們就看不到沒有全球報銷、患者獲得和廣泛使用 donanemab 的情況。

We noted last year that we had low expectations for the use of donanemab during the period between potential accelerated approval and the availability of confirmatory Phase III data in mid-2023. We're disappointed with the position that Centers for Medicare and Medicaid Services has taken in its draft national coverage determination decision, and those low expectations could now extend for some months beyond the TRAILBLAZER-ALZ 2 readout if reconsideration of CMS coverage determination is required, given historical timelines for this process. While the accelerated approval pathway was instituted by the FDA to allow for earlier approval of drugs that treat serious conditions and fill an unmet medical need, hence providing valuable access to more patients faster than what is available under clinical trials, the NCD as currently written essentially negates that patient benefit in Alzheimer's disease.

去年我們注意到，在潛在的加速批准和 2023 年中期確認性 III 期數據的可用性之間，我們對使用 donanemab 的期望很低。我們對醫療保險和醫療補助服務中心在其國家覆蓋範圍確定決定草案中所採取的立場感到失望，如果需要重新考慮 CMS 覆蓋範圍確定，這些低期望現在可能會在 TRAILBLAZER-ALZ 2 讀數之後延長幾個月，給定這個過程的歷史時間表。雖然 FDA 制定了加速批准途徑，以允許更早批准治療嚴重疾病和滿足未滿足醫療需求的藥物，從而比臨床試驗更快地為更多患者提供有價值的訪問，但目前編寫的 NCD 基本上否定了患者對阿爾茨海默病的益處。

Still, we intend to complete our application for accelerated approval for donanemab yet this year, but we now move completion of the accelerated approval submission out of Q1. We expect further volatility and expectations as competitor Alzheimer's disease trials read out prior to our definitive data. We remain confident in the differentiation of donanemab and in our uniquely designed TRAILBLAZER-ALZ 2 study and importantly, the long-term opportunity to help patients with donanemab remains unchanged.

儘管如此，我們仍打算在今年完成對 donanemab 的加速批准申請，但我們現在將加速批准提交的完成移出第一季度。隨著競爭對手阿爾茨海默病試驗在我們的最終數據之前宣讀，我們預計會出現進一步的波動和預期。我們對 donanemab 的差異化和我們獨特設計的 TRAILBLAZER-ALZ 2研究仍然充滿信心，重要的是，幫助 donanemab 患者的長期機會保持不變。

Lastly, with respect to our progress with COVID-19 therapies, earlier this year, we submitted a request to the FDA for Emergency Use Authorization for bebtelovimab for treatment of mild to moderate COVID-19 for patients at high risk for progression to severe COVID-19, including hospitalization or death. This is the third antibody we have developed for the treatment of COVID-19, and authentic virus and pseudovirus assays demonstrate that bebtelovimab retains neutralization activity against Omicron as well as all other known variants of concern. We've produced several hundred thousand doses of bebtelovimab and stand ready to supply as needed if this antibody receives EUA from the FDA.

最後，關於我們在 COVID-19 療法方面的進展，今年早些時候，我們向 FDA 提交了一份緊急使用授權請求，要求貝特洛昔單抗用於治療進展為嚴重 COVID-19 高風險患者的輕度至中度 COVID-19- 19，包括住院或死亡。這是我們為治療 COVID-19 而開發的第三種抗體，真實的病毒和假病毒檢測表明 bebtelovimab 保留了對 Omicron 以及所有其他已知的關注變體的中和活性。我們已經生產了幾十萬劑 bebtelovimab，如果這種抗體從 FDA 獲得 EUA，我們隨時準備根據需要供應。

In addition, we've also submitted a supplemental NDA for baricitinib for treatment of hospitalized patients with COVID-19 and expect regulatory action by the middle of this year. Baricitinib currently has an EUA for this indication. We're proud of the therapies we've delivered to help combat the COVID-19 pandemic, and we'll continue to do our part as public health needs emerge.

此外，我們還提交了巴瑞替尼的補充 NDA，用於治療 COVID-19 住院患者，並預計在今年年中採取監管行動。 Baricitinib 目前有針對該適應症的 EUA。我們為幫助對抗 COVID-19 大流行而提供的療法感到自豪，隨著公共衛生需求的出現，我們將繼續儘自己的一份力量。

In summary, Q4 was another productive quarter for R&D at Lilly, capping what was an outstanding year of pipeline progress on behalf of patients. Now I'll turn the call back to Dave.

總而言之，第四季度是禮來公司研發的另一個富有成效的季度，代表患者在管道進展方面取得了傑出的一年。現在我將把電話轉回戴夫。

Thanks, Dan. Before we move to Q&A, let me summarize the progress we made during 2021. We delivered strong revenue growth in our core business, propelled by our key growth products. We continue to invest heavily in our pipeline and made significant progress in 2021 generating positive Phase III data for 5 new potential medicines, tirzepatide, donanemab, pirtobrutinib, mirikizumab and lebrikizumab, that we expect we will launch in the next 2 years. We also delivered positive data and launched important new indications for Jardiance and Verzenio while we continue to bolster our pipeline through business development with a focus on new modalities. Finally, we returned $4.35 billion to shareholders via the dividend and share repurchases and for the fourth consecutive year, announced a 15% dividend increase.

謝謝，丹。在進行問答之前，讓我總結一下我們在 2021 年取得的進展。在關鍵增長產品的推動下，我們的核心業務實現了強勁的收入增長。我們繼續大力投資於我們的管道，並在 2021 年取得了重大進展，為 5 種新的潛在藥物 tirzepatide、donanemab、pirtobrutinib、mirikizumab 和 lebrikizumab 產生了積極的 III 期數據，我們預計我們將在未來 2 年內推出這些藥物。我們還為 Jardiance 和 Verzenio 提供了積極的數據並推出了重要的新適應症，同時我們繼續通過專注於新模式的業務發展來加強我們的管道。最後，我們通過股息和股票回購向股東返還了 43.5 億美元，並連續第四年宣布增加 15% 的股息。

As we move into 2022, we are excited to continue the progress of turning pipeline value into cash flow, starting with the potential launch of tirzepatide and the submissions of donanemab, pirtobrutinib, mirikizumab and lebrikizumab. These opportunities remind us that our purpose has never been more relevant and highlight the promise of turning science into treatments or cures for some of the most challenging human diseases like diabetes, obesity, Alzheimer's, cancers and autoimmune disorders. We are steadfast in our commitment to improve the lives of millions of patients who rely on us and are confident in our business outlook.

隨著我們進入 2022 年，我們很高興能夠繼續將管道價值轉化為現金流，首先是 tirzepatide 的潛在推出以及 donanemab、pirtobrutinib、mirikizumab 和 lebrikizumab 的提交。這些機會提醒我們，我們的目標從未如此重要，並強調了將科學轉化為治療或治愈一些最具挑戰性的人類疾病（如糖尿病、肥胖症、阿爾茨海默氏症、癌症和自身免疫性疾病）的承諾。我們堅定地致力於改善數百萬依賴我們並對我們的業務前景充滿信心的患者的生活。

So now I'll turn the call over to Kevin to moderate the Q&A session.

所以現在我將把電話轉給 Kevin 來主持問答環節。

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

謝謝，戴夫。 （操作員說明）Lois，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) And our first question is from Seamus Fernandez from Guggenheim.

（操作員說明）我們的第一個問題來自古根海姆的 Seamus Fernandez。

So first, Dan, can you just give us a little bit of the thought process for pushing out the accelerated filing for donanemab? It certainly makes sense, but how much did the NCD actually work into that calculus versus needs or requests from the agency for additional data?

那麼首先，Dan，你能不能給我們一些關於推出加速申請 donanemab 的思考過程？這當然是有道理的，但是 NCD 實際在該計算中發揮了多少作用，而不是該機構對額外數據的需求或請求？

And then the second question, just really wanted to get a better understanding of where you guys think -- the SURMOUNT-1 data sets, where the thresholds would be. We're seeing 68-week data from Wegovy coming in at about 15% to 17% in a nondiabetic patient population. Just wanted to get a sense of some of the pushes and pulls that we should be thinking about in the context of the SURMOUNT-1 data set.

然後是第二個問題，只是想更好地了解你們的想法——SURMOUNT-1 數據集，閾值在哪裡。我們看到來自 Wegovy 的 68 週數據在非糖尿病患者群體中的比例約為 15% 至 17%。只是想了解我們應該在 SURMOUNT-1 數據集的上下文中考慮的一些推動和拉動。

Thanks, Seamus. We'll go to Dan for the question on accelerated approval time line and then Mike Mason on expectations for SURMOUNT-1.

謝謝，西莫。我們將向 Dan 詢問有關加快批准時間線的問題，然後向 Mike Mason 詢問對 SURMOUNT-1 的期望。

Yes. Thank you, Seamus. It's a good question. Look, I think, as I said, the purpose of accelerated approval is to try and get medicines to help patients faster. Without access, that benefit is mainly negated, unfortunately, and clearly, a very frustrating period for patients to have approval of a drug and no reimbursement. So the CMS draft NCD proposal weighed heavily in our considerations around timing and clearly reduces some of the ability to help patients faster that we were hoping for with the accelerated approval.

是的。謝謝你，西莫。這是個好問題。聽著，我認為，正如我所說，加速批准的目的是試圖更快地獲得藥物來幫助患者。如果無法獲得，這種好處主要被否定，不幸的是，很明顯，對於患者來說，這是一個非常令人沮喪的時期，即獲得藥物批准而沒有報銷。因此，CMS 的 NCD 提案草案在我們對時間安排的考慮中佔了很大比重，並且明顯降低了我們希望通過加速批准更快地幫助患者的一些能力。

With respect to the other part of your question, which is how about requests from the FDA or new data or anything like that, there are none of those factors here. We haven't had such requests. So it's really about CMS and about our own team's ability to just get all of the data together and get the right amount of safety data compiled in a way that the FDA can analyze. So we'll continue to work towards accelerated approval yet this year but no longer in Q1.

關於你問題的另一部分，即來自 FDA 的請求或新數據或類似的東西，這裡沒有這些因素。我們沒有這樣的要求。因此，這實際上是關於 CMS 以及我們自己的團隊將所有數據匯總在一起並以 FDA 可以分析的方式收集適量的安全數據的能力。因此，今年我們將繼續努力加快審批，但不會在第一季度。

Thanks, Dan. Mike?

謝謝，丹。麥克風？

Yes. Thanks for the question. We are excited to see the SURMOUNT-1 data. There's good theory on why someone who lives with obesity would have greater weight loss on a product like tirzepatide than those that have type 2 diabetes. Those theories tend to play out when we looked at the novo semaglutide step program where those who had -- didn't have type 2 diabetes had 6 or 7 percentage points greater weight loss than those that had type 2 diabetes.

是的。謝謝你的問題。我們很高興看到 SURMOUNT-1 數據。關於為什麼患有肥胖症的人比患有 2 型糖尿病的人使用 tirzepatide 這樣的產品減肥效果更好，有一個很好的理論。當我們查看 novo semaglutide step 計劃時，這些理論往往會發揮作用，其中那些患有 - 沒有患有 2 型糖尿病的人的體重減輕比患有 2 型糖尿病的人高 6 或 7 個百分點。

We don't know what it's going to turn out to be for SURMOUNT-1. We do believe that it's going to be higher in the non-type 2 diabetes patient than what we saw in the SURPASS studies. Good thing is we don't have to wait too long for those results. We expect those in the first half of this year. And so we'll be patient and look forward to the results, and I think we'll be excited by what we see.

我們不知道 SURMOUNT-1 會變成什麼樣子。我們確實相信，非 2 型糖尿病患者的發病率會高於我們在 SURPASS 研究中看到的情況。好消息是我們不必為這些結果等待太久。我們預計在今年上半年。所以我們會耐心等待結果，我想我們會對我們所看到的感到興奮。

Thanks, Mike. Seamus, thanks for your question.

謝謝，邁克。 Seamus，謝謝你的提問。

And the next caller is Ronny Gal from Bernstein.

下一個來電者是來自 Bernstein 的 Ronny Gal。

The first one is around the N3pG4 in early AD. You're starting a second agent fairly quickly. Can you talk about other distinguishing features for this product versus donanemab? Is it just that it removes plaque best? Are there also others? For example, is it removing preferentially parenchymal plaque versus vascular plaque?

第一個是在公元早期的 N3pG4 附近。您正在相當快地啟動第二個代理。您能談談該產品與多那麥的其他顯著特徵嗎？僅僅是它最好地去除牙菌斑嗎？還有其他人嗎？例如，它是否優先去除實質斑塊而不是血管斑塊？

And the second, you kind of mentioned your expectation for the NCD, but can you confirm to us that you do not expect the NCD to materially change in its final form versus the draft form? And if you can talk a little bit about the process of requesting a change to that entity once we have confirmatory data for the amyloid beta-removing drugs.

第二，您提到了您對 NCD 的期望，但您能否向我們確認您不希望 NCD 的最終形式與草案形式發生重大變化？一旦我們獲得了β澱粉樣蛋白去除藥物的確認數據，您能否談談請求更改該實體的過程。

Thanks, Ronny. We'll go to Dan for the first question on N3pG4 and then Anne for the question on the NCD expectations.

謝謝，羅尼。第一個問題是關於 N3pG4 的問題，我們先問丹，然後問安妮，問關於 NCD 預期的問題。

Yes. Thanks, Ronny. On N3pG4, originally, we started working on this molecule because of antidrug antibodies that we saw and continue to see against donanemab. Because of those ADAs, we've dosed donanemab at pretty high levels. And that in combination with the formulation of donanemab have precluded the ability of generating a subcutaneous dosing form. So that was an important consideration, those 2 things I would say, for development of N3pG4.

是的。謝謝，羅尼。最初，在 N3pG4 上，我們開始研究這種分子，因為我們看到並繼續看到針對多納奈馬的抗藥抗體。由於這些 ADA，我們已經以相當高的水平服用了 donanemab。並且這與多那奈單抗的配方相結合已經排除了產生皮下給藥形式的能力。所以這是一個重要的考慮因素，我想說的這兩件事，對於 N3pG4 的開發。

It binds the same epitope as donanemab. So our understanding and data suggests that it clears exactly the same types of plaques. That's important to us. I think we've seen compelling efficacy here in TRAILBLAZER from donanemab, and we want more of the same in the next molecule. So no differences here in type of plaque. I think speed of plaque removal, our expectations are it should be similar to donanemab, which is to say quite rapid. And the big advantage here is likely to be around dosing and administration.

它與多那奈單抗結合相同的表位。所以我們的理解和數據表明它清除了完全相同類型的斑塊。這對我們很重要。我認為我們已經在 donanemab 的 TRAILBLAZER 中看到了令人信服的功效，我們希望在下一個分子中具有更多相同的功效。所以這裡的斑塊類型沒有區別。我認為去除牙菌斑的速度，我們的預期是應該和多那奈單抗差不多，也就是說相當快。這裡最大的優勢可能在於劑量和給藥。

Thanks, Dan. Anne?

謝謝，丹。安妮？

Well, thanks, Ronny. We believe more than likely the final NCD in April may not change very much. Really what matters most to us is ensuring rapid availability of donanemab for patients with that confirmatory Phase III data. And so that's going to be our focus with CMS. We believe that well-designed and controlled registration trials like TRAILBLAZER-ALZ and ALZ 2 should certainly provide sufficient evidence of clinical benefit for donanemab and that a CD is not needed or appropriate for donanemab.

好吧，謝謝，羅尼。我們認為 4 月份的最終非傳染性疾病很可能不會有太大變化。對我們而言，真正最重要的是確保為具有確認性 III 期數據的患者快速提供多那單抗。所以這將是我們對 CMS 的關注。我們認為，像 TRAILBLAZER-ALZ 和 ALZ 2 這樣精心設計和對照的註冊試驗當然應該提供足夠的證據來證明 donanemab 的臨床益處，並且對於 donanemab 不需要或不適合 CD。

We're also going to see confirmation with CMS, really to your question, once this Phase III efficacy and safety have been established, that donanemab and other medicines with this level of verified evidence would be fully covered by CMS. And we want that path for this coverage to be clearly laid out. As Dan mentioned, it may take some months after the TB 2 readout to work through that, but we'll certainly focus on that. We have been and will continue to meet with CMS to make our points known and to work through what that process is.

對於您的問題，我們還將看到 CMS 的確認，一旦確定了這一 III 期療效和安全性，CMS 將完全涵蓋具有這種水平驗證證據的多納奈馬和其他藥物。我們希望清楚地展示這種覆蓋的路徑。正如丹所說，在 TB 2 讀數後可能需要幾個月的時間才能解決這個問題，但我們肯定會專注於這一點。我們已經並將繼續與 CMS 會面，以表達我們的觀點並完成該過程。

And I think our -- I think as Dan alluded to, what we believe is that with Phase III confirmatory data and ultimately, an FDA traditional approval, we cannot envision a reason why CMS would treat Alzheimer's disease differently than any other class of medicines. I mean this would really be unprecedented. And I believe the pushback from the patient community, from their caregivers and from those that advocate for them would be significant and CMS would have, we believe, no choice but to change it. So our focus is on that Phase III data.

我認為我們的 - 我認為正如 Dan 所暗示的那樣，我們認為，憑藉 III 期確認數據以及最終獲得 FDA 的傳統批准，我們無法想像 CMS 治療阿爾茨海默病的原因與任何其他類別的藥物不同。我的意思是這真的是前所未有的。而且我相信來自患者社區、他們的護理人員和支持他們的人的抵制將是巨大的，我們相信 CMS 將別無選擇，只能改變它。所以我們的重點是第三階段的數據。

Thanks, Anne. Ronny, thanks for your questions.

謝謝，安妮。羅尼，謝謝你的提問。

The next caller is Vamil Divan from Mizuho Securities.

下一位來電者是瑞穗證券的 Vamil Divan。

Maybe one follow-up on donanemab and then one other one unrelated. So in terms of -- obviously, I appreciate what you're saying around the accelerated approval and kind of changing your time line there. I'm just wondering what TRAILBLAZER 4 and if there's any reason -- I'm kind of wondering what the rationale for that trial is now given the limited uptake of Aduhelm to this point. I know we get data later this year, but I'm just wondering what makes -- if there's any sort of change in strategy or thinking around the need for that trial and what exactly that might accomplish?

也許是對 donanemab 的一項後續行動，然後是另一項無關的後續行動。所以就 - 顯然，我很欣賞你所說的加速批准和在那裡改變你的時間線。我只是想知道什麼是 TRAILBLAZER 4 以及是否有任何原因——我有點想知道現在該試驗的基本原理是什麼，因為到目前為止 Aduhelm 的吸收有限。我知道我們會在今年晚些時候獲得數據，但我只是想知道是什麼原因造成的——如果戰略有任何改變，或者考慮是否需要進行試驗，以及這可能會實現什麼？

And then my second question, sort of unrelated. You mentioned around Olumiant the updates from last week, but you also have submitted for alopecia areata. I'm just wondering if you could maybe just talk a little bit about what you see for the potential, I guess, for the JAK class overall in that space but also for Olumiant specifically just given obviously the safety concerns we've seen around that product and the class from before.

然後我的第二個問題，有點不相關。您在 Olumiant 周圍提到了上週的更新，但您也提交了斑禿。我只是想知道你是否可以稍微談談你所看到的潛力，我猜，對於 JAK 類在該領域的整體情況，而且對於 Olumiant，特別是考慮到我們已經看到的安全問題。以前的產品和類。

Thanks, Vamil. We'll go to Dan for the question on TRAILBLAZER 4 and then Patrik for your question on alopecia areata.

謝謝，瓦米爾。我們將向 Dan 詢問有關 TRAILBLAZER 4 的問題，然後向 Patrik 詢問您有關斑禿的問題。

Yes. Thanks, Vamil. You raised a good point on TRAILBLAZER 4, which is a head to head against Aduhelm. Of course, there was a lot of excitement and patient interest and investigator interest in this trial because it's 2 drugs compared to each other. So -- on the other hand, as you point out, from a commercial perspective, the importance of showing superiority to Aduhelm may have dramatically diminished, but that's okay.

是的。謝謝，瓦米爾。你在 TRAILBLAZER 4 上提出了一個很好的觀點，這是與 Aduhelm 的正面交鋒。當然，這項試驗引起了很多興奮和患者的興趣以及研究者的興趣，因為它是兩種藥物的相互比較。所以——另一方面，正如你所指出的，從商業角度來看，向 Aduhelm 展示優勢的重要性可能已經大大降低，但這沒關係。

We're still committed to doing this trial. I think from a scientific perspective, there'll be important conclusions. We have a hypothesis, for example, that the more rapid and deep plaque clearance could lead to greater improvements on biomarkers. I think those kinds of assessments can only be done in a head-to-head study. So this will still be an important contribution to our overall understanding of Alzheimer's disease.

我們仍然致力於進行這項試驗。我認為從科學的角度來看，會有重要的結論。例如，我們有一個假設，即更快和更深的斑塊清除可能會導致生物標誌物的更大改進。我認為這些評估只能在面對面的研究中進行。因此，這仍將是我們對阿爾茨海默病的全面了解的重要貢獻。

Thanks, Dan. Patrik?

謝謝，丹。帕特里克？

Thank you very much for the question. Well, we submitted Olumiant for alopecia areata to the FDA late last year, and it's now submitted to most of European and the Japanese regulatory bodies. There are currently no treatments approved for alopecia areata so we have an opportunity here to be first in disease with Olumiant. And we have been encouraged with the data that we have seen from both BRAVE 1 and BRAVE 2, both based upon physician assessment as well as self-assessment by patients.

非常感謝您的提問。嗯，我們去年底向 FDA 提交了用於治療斑禿的 Olumiant，現在它已經提交給了大多數歐洲和日本的監管機構。目前沒有批准用於斑禿的治療方法，因此我們有機會成為 Oluminant 的第一個治療方法。我們對 BRAVE 1 和 BRAVE 2 的數據感到鼓舞，這些數據均基於醫生評估和患者的自我評估。

And there is truly an unmet need in this space. We have currently approximately 360,000 patients diagnosed in the U.S., and we believe at least 100,000 of those would be eligible for a treatment with JAK. And based upon the profile that we have seen from other assets, we believe that we can launch here with a competitive profile to help patients with alopecia areata.

在這個領域確實存在未滿足的需求。我們目前在美國診斷出大約 360,000 名患者，我們相信其中至少有 100,000 名有資格接受 JAK 治療。根據我們從其他資產中看到的概況，我們相信我們可以在這裡推出具有競爭力的概況來幫助斑禿患者。

Thanks, Patrik. Vamil, thanks for your questions.

謝謝，帕特里克。瓦米爾，謝謝你的提問。

The next caller is Steve Scala from Cowen.

下一位來電者是來自 Cowen 的 Steve Scala。

I assume that you are deep in labeling discussions on tirzepatide. What questions is FDA asking? Are you anticipating the label to read that tirzepatide is a first-line injectable or for use after other injectables fail? And since another very well managed diabetes competitor has had supply issues, I'm curious where tirzepatide is being manufactured and whether the plant has been inspected.

我假設您對關於 tirzepatide 的討論很感興趣。 FDA問什麼問題？您是否期待標籤上顯示 tirzepatide 是一線注射劑或在其他注射劑失敗後使用？由於另一個管理良好的糖尿病競爭對手出現了供應問題，我很好奇 tirzepatide 的生產地點以及工廠是否經過檢查。

Thanks, Steve. We'll go to Mike Mason for both of those questions.

謝謝，史蒂夫。對於這兩個問題，我們都會去找 Mike Mason。

Thanks, Steve, for the question. The tirzepatide submission in the U.S. is going quite well, no surprises in that. We are not getting any unusual questions.

謝謝史蒂夫，這個問題。在美國提交的 tirzepatide 進展順利，這並不奇怪。我們沒有收到任何不尋常的問題。

We're confident in our supply and confident in our supply chain. We'll be ready for launch. Our -- we did comprehensive studies for our SURPASS-5 pivotal studies for the U.S. So I think that will give us a broad label and the label we need for success. So I think things are progressing quite nicely. We're quite confident going into our launch.

我們對我們的供應充滿信心，對我們的供應鏈充滿信心。我們將準備發射。我們 - 我們為美國的 SURPASS-5 關鍵研究進行了全面研究。所以我認為這會給我們一個廣泛的標籤和我們成功所需的標籤。所以我認為事情進展得很好。我們非常有信心進入我們的發布。

Thanks, Mike. Thanks for the questions, Steve.

謝謝，邁克。謝謝你的問題，史蒂夫。

The next caller is Chris Schott with JPMorgan.

下一位來電者是摩根大通的 Chris Schott。

Maybe just following up on the tirzepatide front. Can you just help maybe also set some expectations of the launch as we think about 2022 into 2023? So maybe specifically, how long should we think about post approval until you'd expect broad coverage of tirzepatide? And when we maybe compare and contrast, I guess, the large -- the last large GLP-1 launch of Ozempic, are there similarities or differences we should think about as we think about kind of the state of the market today, the data you'll have, et cetera? Just to help us -- I think we all think about this is a great long-term opportunity but more just the nearer-term dynamics with that.

也許只是跟進 tirzepatide 前線。當我們考慮 2022 年到 2023 年時，您能否幫忙設定一些發射預期？因此，也許具體來說，在您期望廣泛覆蓋 tirzepatide 之前，我們應該考慮多久後批准？當我們進行比較和對比時，我想，Ozempic 的最後一次大型 GLP-1 發布，在我們考慮今天的市場狀況時，我們應該考慮哪些相似之處或不同之處，你的數據會有，等等？只是為了幫助我們——我認為我們都認為這是一個很好的長期機會，但更多的是近期的動態。

And then my second question was just on insulin in 2022. Can you just elaborate a bit more about how to think about the magnitude of price erosion we could see for that franchise relative to what we saw in 2021? I'm just trying to get a sense of how different is the market dynamic, I guess, this year versus last.

然後我的第二個問題是關於 2022 年的胰島素。您能否詳細說明如何考慮相對於我們在 2021 年看到的特許經營權的價格侵蝕幅度？我只是想了解今年與去年的市場動態有何不同。

Thanks, Chris. We'll go to Mike for both of those questions as well.

謝謝，克里斯。我們也會向 Mike 詢問這兩個問題。

Yes. Thanks for the questions. As we approach the tirzepatide launch, we'll be playing for the long term and making sure that we set the foundations up strongly for long-term success. When you have a retail product like this that goes to nearly 100,000 primary care physicians as well as needing broad access, there's little that you can do to really accelerate the launch in the first 6 months. You're also working to get access and having support programs so patients will have a good out-of-pocket experience at launch. And so I wouldn't look for the first 6 months to see a real accelerated uptake of net revenue versus other GLPs in that first 6 months. I think that will be a focus for us of just laying the strong foundations, being patient focused, getting access, driving awareness through a broad subset of physicians. That will give us that foundation to be successful long term.

是的。感謝您的提問。隨著我們接近 tirzepatide 的發布，我們將長期參與，並確保我們為長期成功奠定堅實的基礎。當您擁有這樣的零售產品，該產品面向近 100,000 名初級保健醫生並且需要廣泛的訪問權限時，您幾乎無法在前 6 個月內真正加速推出。您還在努力獲得訪問權限並製定支持計劃，以便患者在發佈時獲得良好的自付費用體驗。因此，與其他 GLP 在前 6 個月相比，我不會期待前 6 個月的淨收入真正加速增長。我認為這將是我們的一個重點，即奠定堅實的基礎、以患者為中心、獲得訪問權、通過廣泛的醫生群體提高意識。這將為我們提供長期成功的基礎。

And then on insulin, when we look at the Q4 results, we did have in particular a greater-than-usual decline in our price, and that was really due to kind of a double-whammy effect. We have significant adjustments from our gross sales to our net sales. And so if our estimates are off just a little bit, that could have a significant impact on our net revenues. And so what we saw actually was that in the comparison period, in Q4 of 2020, we've experienced some positive onetime gains, and then in this quarter, we saw some negative onetime adjustments. So that's what led to what looks like a greater-than-expected net sales decline.

然後在胰島素方面，當我們查看第四季度的結果時，我們的價格確實出現了比平時更大的下降，這實際上是由於一種雙重打擊效應。我們從總銷售額到淨銷售額進行了重大調整。因此，如果我們的估計稍有偏差，那可能會對我們的淨收入產生重大影響。所以我們實際上看到的是，在比較期間，在 2020 年第四季度，我們經歷了一些積極的一次性收益，然後在本季度，我們看到了一些負面的一次性調整。因此，這就是導致淨銷售額下降似乎大於預期的原因。

And I think for our portfolio, we have provided guidance that we would be at about mid-single-digit decline. I think we'll see that greater for insulin than our net portfolio, but I don't see anything largely unexpected in '22 versus where we've seen the trends over the last couple of years.

我認為對於我們的投資組合，我們已經提供了大約中個位數下降的指導。我認為我們會看到胰島素比我們的淨投資組合更大，但與過去幾年我們看到的趨勢相比，我認為 22 年沒有任何出乎意料的事情。

Maybe just to add something there, Chris. That's -- a dynamic as well is patient assistance. And as you know, Lilly has led, over the last 3 years, with a number of solutions to reduce out-of-pocket costs given the problems in the insurance markets. And those have been, in addition to the normal competitive dynamics in terms of gross to net, an important solution for patients -- actually, out-of-pocket costs for -- correct me, Mike, if I get this wrong, for patients in the U.S. dropped over the last 3 years from $34 to $21 per month on average for Lilly insulins. That's quite a bit lower than our competitors.

也許只是為了在那裡添加一些東西，克里斯。那是 - 一個動態以及病人的援助。如您所知，鑑於保險市場存在的問題，禮來公司在過去 3 年中率先推出了多種解決方案來降低自付費用。除了從毛到淨值方面的正常競爭動態之外，這些對於患者來說是一個重要的解決方案——實際上，是自付費用——糾正我，邁克，如果我弄錯了，對於患者在過去 3 年裡，禮來胰島素在美國的平均每月費用從 34 美元降至 21 美元。這比我們的競爭對手低很多。

But that does hit the price line for us, either through the now 70% off insulin lispro product, which is available, or through the buy-downs we do at the point of sale to $35 per month. So that's in the background. There is sort of a terminal quantity to that but we have seen good adoption. And I guess the good news is patients are taking advantage of that and it's showing up and retaining volume. It does hit the net price line though.

但這確實觸及了我們的價格線，無論是通過現在可用的賴脯胰島素產品 70% 的折扣，還是通過我們在銷售點進行的每月 35 美元的降價購買。所以這是在後台。有一種終端數量，但我們已經看到了良好的採用。我想好消息是患者正在利用這一點，並且它正在出現並保持體積。不過，它確實觸及了淨價格線。

Thanks, Dave and Mike. Chris, thanks for your questions.

謝謝，戴夫和邁克。克里斯，謝謝你的提問。

The next caller is Tim Anderson from Wolfe Research.

下一位來電者是來自 Wolfe Research 的 Tim Anderson。

This is Alice Nettleton on for Tim Anderson. So a question on donanemab. The premise of donanemab is that you only dose to plaque negativity. However, to determine plaque negativity, you need a minimum of 2 PET scans and quite possibly 3, maybe even more. The CMS draft guidance only covers 1. Even if it ultimately gets revised to be more generous, if it doesn't also include increased coverage of PET scanning, then you could argue Lilly is uniquely disadvantaged versus competitors. Would be curious to hear your thoughts on this.

這是蒂姆安德森的愛麗絲內特爾頓。所以關於donanemab的問題。 donanemab 的前提是您只對斑塊負性進行給藥。然而，要確定斑塊陰性，您需要至少 2 次 PET 掃描，很可能需要 3 次，甚至更多。 CMS 指南草案僅涵蓋 1。即使最終修訂得更加慷慨，如果它不包括增加 PET 掃描的覆蓋範圍，那麼您可能會認為禮來公司與競爭對手相比處於獨特的劣勢。很想听聽您對此的看法。

Thanks, Alice. We'll go to Anne White for that question.

謝謝，愛麗絲。我們會去找安妮懷特來回答這個問題。

Well, thanks. And as you said, we're pleased that CMS acknowledged that there is an important role for amyloid PET in patient identification. We certainly agreed to that as well. And using amyloid PET to monitor plaque reduction and then confirm clearance is incredibly important, we believe, for patients receiving these therapies and incredibly important for the health care system because it provides clarity as to when you can essentially stop dosing of medicine. Once you've cleared the target, we believe that's the time to stop dosing. And as you know, in our data, we've shown that 40% even clear their plaque in 6 months.

非常感謝。正如您所說，我們很高興 CMS 承認澱粉樣蛋白 PET 在患者識別中的重要作用。我們當然也同意這一點。我們認為，使用澱粉樣蛋白 PET 監測斑塊減少，然後確認清除非常重要，對於接受這些治療的患者來說，對於醫療保健系統也非常重要，因為它清楚地說明了何時可以基本上停止服藥。一旦您清除了目標，我們認為該是停止給藥的時候了。如您所知，在我們的數據中，我們已經表明 40% 的人甚至在 6 個月內清除了他們的牙菌斑。

So incredibly important, we believe that the value that, that brings to the health care system far outweighs any cost that it might bring, and we've done those analyses. So it's very, very clear that when you take into account all the costs of these medicines, the infusion, the safety monitoring, you're much better off with clarity of when that plaque is cleared and stopping dosing. It's a unique attribute of donanemab that we've certainly talked to CMS and others about and they've recognized. So we believe the value proposition here is quite strong and look forward to working with CMS to get the amyloid PET CED revised in the near future.

非常重要，我們相信這給醫療保健系統帶來的價值遠遠超過它可能帶來的任何成本，我們已經完成了這些分析。因此，非常非常清楚的是，當您考慮到這些藥物、輸液、安全監測的所有成本時，您最好清楚何時清除斑塊並停止給藥。這是 donanemab 的一個獨特屬性，我們當然已經與 CMS 和其他人討論過並且他們已經認識到了。因此，我們認為這裡的價值主張非常強大，並期待與 CMS 合作，在不久的將來修訂澱粉樣蛋白 PET CED。

Thanks, Anne. Alice, thanks for your question.

謝謝，安妮。愛麗絲，謝謝你的提問。

The next caller is Andrew Baum with Citi.

下一位來電者是花旗的 Andrew Baum。

A question on lebrikizumab and then one on Verzenio. So on lebrikizumab, part of the premise in terms of differentiation versus dupi, given the IL-13 mechanism, is a lower instance of ocular events, particularly conjunctivitis, which are frequent with dupi and patient problematic. I know you haven't fully shared the data, but I wonder whether you could talk to whether the data will support that premise and positioning in the market.

一個關於 lebrikizumab 的問題，然後一個關於 Verzenio 的問題。因此，在 lebrikizumab 上，考慮到 IL-13 機制，在區分與 dupi 方面的部分前提是眼部事件的較低實例，尤其是結膜炎，這在 dupi 和患者問題中很常見。我知道您尚未完全共享數據，但我想知道您是否可以談談數據是否會支持該前提和市場定位。

And then second, in relation to Verzenio. Given you're now rolling it out for the adjuvant setting, could you talk to what are the key barriers to adoption among oncologists? Is it tolerability in the adjuvant setting? Is it screening for the Ki-67 patients or some -- or the financial factors? And how can you resolve them?

其次，關於 Verzenio。鑑於您現在正在將其推廣用於輔助設置，您能否談談腫瘤學家採用的主要障礙是什麼？它在輔助環境中是否具有耐受性？是篩查 Ki-67 患者還是某些——還是經濟因素？你怎麼能解決它們？

Thanks, Andrew. We'll go to Patrik for the question on lebrikizumab and then Jake for the question on Verzenio.

謝謝，安德魯。我們將向 Patrik 詢問有關 lebrikizumab 的問題，然後向 Jake 詢問有關 Verzenio 的問題。

Thank you very much, Andrew. Based upon the data that we've seen so far, we believe that we have a competitive asset with the market leader for atopic dermatitis. And we were very encouraged with the efficacy results with more than 50% of the patients achieving at least an EASI of 75. And also consistent across all the different measures, IGA, EASI and Pruritus NRS, it met all the key secondary endpoints.

非常感謝你，安德魯。根據我們迄今為止看到的數據，我們相信我們擁有與特應性皮炎市場領導者競爭的資產。我們對療效結果感到非常鼓舞，超過 50% 的患者的 EASI 至少達到 75。並且在所有不同的措施（IGA、EASI 和 Pruritus NRS）中也保持一致，它滿足了所有關鍵的次要終點。

Specific to your question on conjunctivitis, we need to wait for the 52-week data. In the induction data, we didn't see any difference to existing biologics. But the cases that we saw were all mild to moderate. And 1/3 of those had a history of conjunctivitis, and only a few of them discontinued treatment. So we are looking forward to the database lock of the maintenance treatment during the second -- first half of this year.

具體到你關於結膜炎的問題，我們需要等待52週的數據。在誘導數據中，我們沒有看到與現有生物製劑的任何差異。但我們看到的病例都是輕度到中度的。其中1/3有結膜炎病史，只有少數人停止治療。所以我們很期待今年下半年——上半年維護處理的數據庫鎖。

Thanks, Patrik. Jake?

謝謝，帕特里克。傑克？

Yes. Thanks for the question. So I think as it relates to the key barriers to adoption, I think the biggest one in the overlay, and then I'll get more specific, is just that this represents really the first new standard of care in this setting in 20 years. And so there are just a lot of physicians who have entrenched behavior and comfort with what they're doing. And so the first barrier is really around education and getting a comfort level-changing behavior. And so that -- we have a lot of tactics in place to do that, to make sure that the data on the agent are known and to answer questions that physicians may have.

是的。謝謝你的問題。所以我認為，由於它與採用的關鍵障礙有關，我認為覆蓋中最大的障礙，然後我會更具體地講，這真的代表了 20 年來這個環境中的第一個新的護理標準。所以只有很多醫生有根深蒂固的行為並且對他們正在做的事情感到安慰。因此，第一個障礙實際上是圍繞教育和獲得改變舒適度的行為。所以——我們有很多策略來做到這一點，以確保代理的數據是已知的，並回答醫生可能提出的問題。

More specifically, you highlighted a few things that are good things to know, which is the Ki-67 testing requirement and the interpretation of those results and integrating them into patient selection is a new thing for docs in this setting; as well as the diarrhea management, which is a real phenomenon with Verzenio. We have protocols in place that allow it to be managed, and it tends to be a short-term side effect that can be managed. But there are a lot of physicians out there who've literally never written a prescription of Verzenio because they've been historically large IBRANCE users. And for that segment in particular, there's an education component to get them comfortable and ensure they're using the protocols that we think work really well for diarrhea management. That all having been said, we're happy with what we're seeing so far, but it is early days obviously in this launch trajectory.

更具體地說，您強調了一些值得了解的好事情，即 Ki-67 測試要求以及對這些結果的解釋並將它們整合到患者選擇中對於這種情況下的醫生來說是一件新事物；以及腹瀉管理，這是 Verzenio 的真實現象。我們制定了允許對其進行管理的協議，並且它往往是可以管理的短期副作用。但是有很多醫生實際上從未開過 Verzenio 的處方，因為他們在歷史上一直是 IBRANCE 的大量用戶。特別是對於該部分，有一個教育部分可以讓他們感到舒適並確保他們使用我們認為對腹瀉管理非常有效的協議。說了這麼多，我們對到目前為止所看到的感到滿意，但顯然在這個發射軌跡中還處於早期階段。

Thanks, Jake. Andrew, thanks for your questions.

謝謝，傑克。安德魯，謝謝你的提問。

The next caller is Geoff Meacham from Bank of America.

下一位來電者是美國銀行的 Geoff Meacham。

Just have a couple of quick ones. For tirzepatide in obesity, what investments have to be made to help evolve the payer attitudes towards obesity as more of a medical condition? Obviously, it has a lot to do with benefit/risk, starting with SURMOUNT-1, and you have a competitor leading the charge as well.

只要有幾個快速的。對於肥胖症中的 tirzepatide，必須進行哪些投資來幫助改變付款人對肥胖症作為一種醫療狀況的態度？顯然，它與收益/風險有很大關係，從 SURMOUNT-1 開始，你也有一個競爭對手在領先。

And then the second question is for pirtobrutinib. Was -- the decision to file in MCL, was it based more on unmet need and the opportunity versus regulatory feedback? I want to get a little bit more clarity on that. And with the Phase IIIs in CLL not completing for at least a few years, was there more consideration for those towards an interim look being built in? I'm just trying to think of the potential lag in commercial availability between the 2 indications.

然後第二個問題是關於 pirtobrutinib 的。是否 - 向 MCL 提交申請的決定，是否更多地基於未滿足的需求和機會而不是監管反饋？我想更清楚一點。由於 CLL 的第三階段至少在幾年內沒有完成，是否有更多考慮構建臨時外觀的人？我只是想考慮這兩個適應症之間商業可用性的潛在滯後。

Thanks, Geoff. We'll go to Mike for the first question and then Jake for the second.

謝謝，傑夫。我們先問邁克，然後問傑克第二個問題。

Yes. It's a good question on obesity and what it's going to take to unlock and build that marketplace. When you look at historically, the agent just had kind of limited weight loss. And because of that, they didn't really drive good health outcomes and that limited access, limited physicians from writing that. So we think, first of all, just having an agent like tirzepatide that could have significant and clinically meaningful weight loss is the first step of the evolution of the marketplace and the interest in that, and we've seen that in market research.

是的。這是一個關於肥胖的好問題，以及如何解鎖和建立這個市場。當你從歷史上看時，代理只是有一種有限的體重減輕。正因為如此，他們並沒有真正推動良好的健康結果和有限的訪問，限制醫生寫這些。所以我們認為，首先，只有像 tirzepatide 這樣可以顯著和臨床意義的減肥藥物是市場發展和對此感興趣的第一步，我們已經在市場研究中看到了這一點。

And then we've got to begin to build the evidence to show that significant weight loss from tirzepatide will lead to hard outcomes, and that's what we're doing in our extended indication focus. We've announced a heart failure -- HFpEF study. We announced in December a sleep apnea study as well as an important morbidity/mortality study or MMO study that will look at hard outcomes for other potential outcomes like CV and others. We'll give you more information on that coming up. We also have a chronic kidney disease mechanism-of-action Phase II study that will help demonstrate why tirzepatide may work for that patient population and doing work in NASH.

然後我們必須開始建立證據，以表明替西帕肽顯著減輕體重會導致艱難的結果，這就是我們在擴展適應症重點中所做的事情。我們宣布了一項心力衰竭——HFpEF 研究。我們在 12 月宣布了一項睡眠呼吸暫停研究以及一項重要的發病率/死亡率研究或 MMO 研究，該研究將著眼於其他潛在結果（如 CV 等）的硬性結果。我們將為您提供更多關於即將到來的信息。我們還有一項慢性腎病作用機制 II 期研究，這將有助於證明為什麼 tirzepatide 可能適用於該患者群體並在 NASH 中發揮作用。

And so I think it's important for us to demonstrate -- I think we're confident that -- with the level of weight loss that we'll see with tirzepatide, that, that should lead to hard outcomes. That should then lead to earlier use of an agent like tirzepatide to really slow and disrupt the progression of obesity and really turn this into more of a preventive versus waiting for the heart outcomes to show. But that's going to be the evolution of it. We've got an extensive Phase III program in order to demonstrate the evidence we think we need to -- in order to unlock and grow access over time.

所以我認為對我們來說重要的是證明——我認為我們有信心——我們將看到使用 tirzepatide 的減肥水平，這應該會導致艱難的結果。這應該會導致更早地使用像 tirzepatide 這樣的藥物來真正減緩和破壞肥胖的進展，並真正將其轉變為更多的預防措施，而不是等待心臟結果顯示。但這將是它的演變。我們有一個廣泛的第三階段計劃，以展示我們認為我們需要的證據——以便隨著時間的推移解鎖和增加訪問權限。

Thanks, Mike. Jake, on pirtobrutinib?

謝謝，邁克。傑克，在 pirtobrutinib 上嗎？

Yes. So to the first part of your question around the decision to file for mantle cell, you framed it as was it unmet need versus regulatory feedback. And the answer really is both. So we've had a longitudinal conversation with the agency around this indication, showing them our clinical data at various snapshots over time. And we got to a point where we had agreement on the key components of what an NDA could look like from a clinical package perspective. And so that informed our decision to file.

是的。因此，對於關於申請地幔細胞決定的問題的第一部分，您將其描述為未滿足的需求與監管反饋。答案確實是兩者兼而有之。因此，我們圍繞這一適應症與該機構進行了縱向對話，向他們展示了我們隨著時間推移在各種快照中的臨床數據。從臨床包裝的角度來看，我們已經就 NDA 的關鍵組成部分達成了一致。因此，我們決定提交文件。

In other words, this was not a sort of unilateral Lilly decision. This was done very much in concert with FDA. And I think they and us realized the unmet need of patients in the setting and the potential proposition of pirtobrutinib there. Obviously, the ultimate approval is subject to an FDA review. So nothing's done until it's done, of course.

換句話說，這不是禮來單方面的決定。這與 FDA 非常一致。我認為他們和我們都意識到了患者在該環境中未得到滿足的需求以及 pirtobrutinib 的潛在建議。顯然，最終的批准需要經過 FDA 的審查。因此，當然，在它完成之前什麼都做不了。

As it relates to the potential lag between a mantle cell approval and a CLL approval, I think it's just too early to really comment because the latter, CLL, is really subject to the enrollment dynamics of the Phase III program. And it's just a little too early days for us to really say exactly which one of those studies will be the first to read out and when because it is so enrollment kinetics contingent. So over the course of this year, we'll have a lot more information about that, I presume, and be in a better position to prognosticate about CLL timing.

由於它與套細胞批准和 CLL 批准之間的潛在滯後有關，我認為現在發表評論還為時過早，因為後者 CLL 確實受第三階段計劃的註冊動態的影響。對於我們來說，要真正確切地說出其中哪一項研究將首先公佈以及何時公佈還為時過早，因為它與入學動力學有關。因此，在今年的過程中，我們將獲得更多關於此的信息，我想，並且能夠更好地預測 CLL 時間。

Thanks, Jake. Geoff, thanks for your questions.

謝謝，傑克。傑夫，謝謝你的提問。

The next caller is Louise Chen from Cantor.

下一位來電者是來自 Cantor 的 Louise Chen。

So my first question is on lebrikizumab. If it's approved, do you expect sales to come from share gains from DUPIXENT or new patient starts? And then second question is on pirtobrutinib. Do you see an opportunity for the drug in first-line treatment? And if so, do you think you need to wait for the head-to-head results before that becomes a meaningful opportunity for you?

所以我的第一個問題是關於lebrikizumab。如果獲得批准，您預計銷售額將來自 DUPIXENT 或新患者開始的份額收益嗎？然後第二個問題是關於 pirtobrutinib。您是否看到該藥物在一線治療中的機會？如果是這樣，你認為你需要等待正面交鋒的結果，然後才能成為對你有意義的機會嗎？

Thanks, Louise. We'll go to Patrik for the question on lebrikizumab's source of business and then back to Jake on pirtobrutinib.

謝謝，路易絲。我們將向 Patrik 詢問有關 lebrikizumab 業務來源的問題，然後再向 Jake 詢問有關 pirtobrutinib 的問題。

Thank you very much, Louise. I think first and foremost, if we look at the atopic dermatitis space, it's pretty much where psoriasis was a decade ago. And we see a very low biologic penetration into those patients in need of treatment beyond topicals today. So we definitely see an opportunity to significantly grow the market in atopic dermatitis. But as I mentioned earlier, we also believe that we have an asset here that is very competitive with the market leader. So I would foresee that we will see an uptick both in terms of -- driven by market growth as well as competing very successfully with DUPIXENT.

非常感謝你，路易絲。我認為首先，如果我們看看特應性皮炎領域，它幾乎與十年前的牛皮癬一樣。而且我們看到，如今那些需要外用治療的患者的生物滲透率非常低。因此，我們絕對看到了顯著增長特應性皮炎市場的機會。但正如我之前提到的，我們也相信我們在這裡擁有與市場領導者非常有競爭力的資產。因此，我預計我們將在市場增長的推動下以及與 DUPIXENT 非常成功地競爭方面看到上升。

Thanks, Patrik. Jake?

謝謝，帕特里克。傑克？

So the pirtobrutinib opportunity we see primarily and certainly initially is in patients who have been previously treated with a BTK inhibitor or more. Obviously, we think there's a potential for the drug in the first line, and that's why we're running studies there.

因此，我們主要而且肯定最初看到的 pirtobrutinib 機會是在先前接受過 BTK 抑製劑或更多抑製劑治療的患者身上。顯然，我們認為這種藥物有潛力作為一線藥物，這就是我們在那裡進行研究的原因。

We have 2 studies that we're running in first-line CLL. One is, as you mentioned, a head-to-head study against ibrutinib. The other -- which will take a long time to read out because of the natural history of the control arm. The other is a study we just recently started against chemoimmunotherapy. That study will read out much, much quicker and, therefore, allow for the drug to be labeled in the first-line setting.

我們在一線 CLL 中進行了 2 項研究。正如你所提到的，一個是針對伊布替尼的頭對頭研究。另一個——由於控制臂的自然歷史，需要很長時間才能讀出。另一項是我們最近開始的一項針對化學免疫療法的研究。該研究將更快地讀出結果，因此允許在一線環境中標記藥物。

And I think what we've learned particularly from other newer entrants in this space is that you really need to generate a differentiating data set in some way, shape or form and then have the labeled indications that allow physicians and patients to have choice. And I think in particular, the Calquence acalabrutinib program has shown that you really actually don't necessarily need direct head-to-head data to suggest differentiation or for at least physicians to perceive differentiation in different drugs so long as you have a labeled indication that allows for on-label prescribing and reimbursement. So one of the reasons that we initiated the first-line chemoimmunotherapy study was to have a path to that first-line label more quickly and allow patients and physicians to make choices.

我認為我們從該領域的其他新進入者那裡學到的特別是，您確實需要以某種方式、形狀或形式生成差異化的數據集，然後擁有允許醫生和患者選擇的標記適應症。我特別認為，Calquence acalabrutinib 計劃表明，只要您有標記的適應症，您實際上並不一定需要直接的頭對頭數據來建議差異化，或者至少讓醫生感知不同藥物的差異化這允許標籤上的處方和報銷。因此，我們啟動一線化學免疫療法研究的原因之一是為了更快地獲得一線標籤，並允許患者和醫生做出選擇。

Thanks, Jake. Louise, thanks for your questions.

謝謝，傑克。路易絲，謝謝你的提問。

The next caller is Umer Raffat with Evercore ISI.

下一位來電者是 Evercore ISI 的 Umer Raffat。

This is Mike in for Umer. Just 2 for me. One on tirzepatide. If tirzepatide is priced at a slight premium over Trulicity on a list basis, that could theoretically mean a massive increase on a net basis. So given where prices are paid in government channels for Trulicity, can you remind us what percent of Trulicity is Medicare, Medicaid and VA? And how different is that price versus your commercial price?

這是 Umer 的 Mike。對我來說只有2個。一個關於替西帕肽。如果 tirzepatide 在列表基礎上的定價略高於 Trulicity ，理論上這可能意味著淨額大幅上漲。因此，鑑於政府渠道為 Trulicity 支付的價格，您能否提醒我們，醫療保險、醫療補助和 VA 佔 Trulicity 的百分比是多少？該價格與您的商業價格有何不同？

And switching gears to donanemab. For TRAILBLAZER 3, I was wondering if you guys had finalized the stat methodology for assessing the primary endpoint. I know a little while back, you had a nice poster on TRAILBLAZER 2 showing how the primary endpoints were assessed via Bayesian analysis versus MMRM. Just kind of remind us where -- if anything has been finalized for the methodology for assessing the primary endpoint in TRAILBLAZER 3?

並切換到donanemab。對於 TRAILBLAZER 3，我想知道你們是否已經確定了評估主要終點的統計方法。我知道不久前，您在 TRAILBLAZER 2 上有一張不錯的海報，展示瞭如何通過貝葉斯分析與 MMRM 評估主要終點。只是提醒我們在哪裡 - 是否已經為評估 TRAILBLAZER 3 中的主要終點的方法最終確定了什麼？

Thanks, Mike. We'll go to Mike Mason for the questions around tirzepatide pricing and Trulicity segments in the U.S. and then Dan for the question on TRAILBLAZER 3. Mike?

謝謝，邁克。我們將向 Mike Mason 詢問有關美國的 tirzepatide 定價和 Trulicity 細分市場的問題，然後向 Dan 詢問有關 TRAILBLAZER 3 的問題。Mike？

Thanks, Mike, for your question. Obviously, I won't be able to talk in too much detail around the list price or [net] price for tirzepatide. Maybe the best way to answer your question is that typically for a new product, you tend to get commercial access first, then Part D, then followed by Medicaid and other channels.

謝謝，邁克，你的問題。顯然，我無法詳細談論替西帕肽的標價或 [淨] 價。也許回答您問題的最佳方式是，通常對於新產品，您往往首先獲得商業訪問權，然後是 D 部分，然後是醫療補助和其他渠道。

And yes, the commercial net prices are typically higher than Part D and Part D is typically higher than Medicaid. So you will see kind of the evolution of any retail product to be a higher net price at the beginning of the life cycle. And then as the lower -- if you reach volume in lower-priced segments, you'll see that decline like we've talked about over -- with Trulicity over the last couple of years.

是的，商業淨價通常高於 D 部分，而 D 部分通常高於 Medicaid。因此，您會看到任何零售產品在生命週期開始時的淨價格都在演變。然後是較低的——如果你在價格較低的細分市場中達到銷量，你會看到我們已經討論過的那種下降——在過去的幾年裡，隨著 Trulicity 的出現。

Now we will have extensive patient support programs in the first 6 months for tirzepatide. So again, I wouldn't be looking too much at that for tirzepatide in the first 6 months. But overall, over the first couple of years, I think any product, you'll see that dynamic. For your specific question on Medicaid, with Trulicity, that's currently around 10% of the volume. Thanks for the question.

現在，我們將在頭 6 個月內為 tirzepatide 提供廣泛的患者支持計劃。再說一次，在頭 6 個月內，我不會過多關注替西帕肽。但總的來說，在最初的幾年裡，我認為任何產品，你都會看到這種動態。對於您關於 Medicaid 的具體問題，Trulicity 目前約佔總量的 10%。謝謝你的問題。

Thanks, Mike. Dan?

謝謝，邁克。擔？

Yes. Thanks, Mike, for the question on TRAILBLAZER 3. It's a good question you raised because this is a really interesting population. These are patients who have amyloid plaque in their brain but they're still cognitively normal. So what kind of endpoint is appropriate for a population like that? In our view, we're looking at progression metrics. So do they progress to a CDR rating that indicates that they now have impairment?

是的。謝謝 Mike，關於 TRAILBLAZER 3 的問題。你提出的問題很好，因為這是一個非常有趣的人群。這些患者的大腦中有澱粉樣蛋白斑塊，但他們的認知仍然正常。那麼什麼樣的端點適合這樣的人群呢？在我們看來，我們正在研究進度指標。那麼他們是否進展到表明他們現在有減值的 CDR 評級？

So it's a bit of a binary outcome for each patient. Did they progress or did they not progress? And then you have an event-driven study with Kaplan-Meier type analysis. So that's how we're thinking about TRAILBLAZER 3 right now. And probably -- we haven't published the design paper yet, but that may yet be forthcoming. And that study is currently enrolling.

因此，對於每個患者來說，這有點二元結果。他們進步了還是沒有進步？然後你有一個使用 Kaplan-Meier 類型分析的事件驅動研究。這就是我們現在對 TRAILBLAZER 3 的看法。並且可能 - 我們還沒有發佈設計文件，但這可能即將發布。該研究目前正在招募中。

Thanks, Dan. Mike, thanks for your questions.

謝謝，丹。邁克，謝謝你的問題。

The next caller is Carter Gould with Barclays.

下一位來電者是 Barclays 的 Carter Gould。

I guess just first for Dan. Maybe to clarify, I mean, the language you're using around no longer Q1. I noticed -- I guess you guys weren't explicitly confirming to 2Q, so just -- maybe just clarifying then. Is that sort of time unknown, just still some time in '22? Or is it just going to kind of spill over by a couple of weeks or months?

我想首先是丹。也許是為了澄清，我的意思是，你使用的語言不再是 Q1。我注意到 - 我猜你們並沒有明確確認 2Q，所以只是 - 也許只是澄清一下。那種時間是未知的，只是在 22 年還有一段時間嗎？或者它只是會溢出幾週或幾個月？

And then maybe for Jake on Tyvyt. When we spoke in December, I thought you were pretty balanced, if not even maybe negative on the prospects for approval based on some of the commentary around data coming out of China. Now that you've got the questions in hand, I don't know if your stance has changed or if you have any additional color to add.

然後可能是關於 Tyvyt 的 Jake。當我們在 12 月談話時，我認為你是相當平衡的，如果根據一些關於來自中國的數據的評論，對批准的前景甚至可能不是負面的。既然您已經掌握了問題，我不知道您的立場是否發生了變化，或者您是否還有其他顏色要添加。

Thanks, Carter. We'll go to Dan for the question on donanemab and then Jake on sintilimab in the U.S.

謝謝，卡特。在美國，我們將向 Dan 詢問有關 donanemab 的問題，然後向 Jake 詢問有關 sintilimab 的問題。

Yes. Thanks, Carter. Exactly -- you noted it correctly, which is that we're saying no longer Q1 and not providing more specificity than that. We do anticipate completing the submission yet this year. I think importantly here, we're trying to take investor focus off of like the exact timing of accelerated approval, given our very limited expectations for the impact of that accelerated approval commercially.

是的。謝謝，卡特。完全正確-您正確地指出了這一點，也就是說，我們說的不再是 Q1，也沒有提供比這更多的特異性。我們確實預計今年會完成提交。我認為重要的是，鑑於我們對加速批准在商業上的影響的期望非常有限，我們正試圖將投資者的注意力從加速批准的確切時間上移開。

We're still pursuing it. We think there's some opportunity to help patients faster through it. But I don't think investors should look at that as a big commercial inflection point. It's really around our ability to communicate the TRAILBLAZER 2 confirmatory Phase III data and then work with CMS, hopefully, before that or immediately after that to make sure there's access once we have that confirmatory data. So that's the timing, I think, investors should be focused on.

我們仍在追求它。我們認為有一些機會可以幫助患者更快地度過難關。但我認為投資者不應將其視為一個重大的商業拐點。這真的是圍繞我們傳達 TRAILBLAZER 2 確認性 III 期數據的能力，然後與 CMS 合作，希望在此之前或之後立即確保我們擁有該確認性數據後可以訪問。所以這是我認為投資者應該關注的時機。

Thanks, Dan. Jake?

謝謝，丹。傑克？

Thanks for the question on sintilimab. So as you know, we have the FDA Advisory Committee meeting with Innovent a week from today. Our position on the matter really hasn't changed nor have our expectations. We believe that the risk/benefit of the agent is demonstrable on the basis of the well-conducted study, and we believe the results of the study are indeed applicable to a U.S. population. And we'll make our case in that respect a week from today.

感謝您對sintilimab 的提問。如您所知，我們將在一周後與 Innovent 舉行 FDA 諮詢委員會會議。我們在這件事上的立場確實沒有改變，我們的期望也沒有改變。我們認為，在進行良好的研究的基礎上，該藥物的風險/收益是可以證明的，並且我們相信該研究的結果確實適用於美國人群。從今天起一周後，我們將在這方面提出我們的意見。

That having been said, we understand the stance of the agency may have changed or maybe we may have misinterpreted it a few years ago. And so we'll await the FDA's presentation on that topic and the feedback from the ODAC members. But we think this product, if approved, could be meaningful for patients in the United States as a result of our disruptive pricing strategy. But we obviously don't know if we'll be able to execute on that.

話雖如此，我們了解該機構的立場可能已經改變，或者我們可能在幾年前誤解了它。因此，我們將等待 FDA 關於該主題的介紹以及 ODAC 成員的反饋。但我們認為，由於我們的顛覆性定價策略，該產品如果獲得批准，可能對美國患者有意義。但我們顯然不知道我們是否能夠執行此操作。

Thanks, Jake. Carter, thanks for your questions.

謝謝，傑克。卡特，謝謝你的提問。

The next caller is Kerry Holford from Berenberg.

下一位來電者是來自 Berenberg 的 Kerry Holford。

Two questions, please. Firstly, on Olumiant, I wonder if you could break out for us the proportion of sales in the quarter that were related to use in COVID and what your expectations are here going forward and also whether you can expand on the discussions you've had with the FDA on the atopic dermatitis indication and why you think a CRL could be forthcoming. If additional studies would be required, would you continue to pursue in this indication?

請教兩個問題。首先，在 Olumiant 上，我想知道您是否可以向我們透露本季度與在 COVID 中使用相關的銷售額比例以及您對未來的期望，以及您是否可以擴展與您進行的討論FDA 關於特應性皮炎適應症以及您認為 CRL 可能即將推出的原因。如果需要額外的研究，您會繼續研究這個適應症嗎？

And then secondly, on (technical difficulty), we obviously have the positive headline data from the Phase III. So I'm wondering when you will publish the full data and whether we'll get to see that ahead of your filings.

其次，在（技術難度）方面，我們顯然擁有第三階段的正面標題數據。所以我想知道你什麼時候會公佈完整的數據，以及我們是否會在你提交文件之前看到這些數據。

Okay. Thanks, Kerry. We'll go to Patrik for those questions.

好的。謝謝，克里。這些問題我們會去找Patrik。

Okay. Thank you very much. Let's start with Olumiant in COVID-19. If you look at the Q4 performance of Olumiant, I think you should assume that the underlying business in rheumatoid arthritis outside of U.S. and atopic dermatitis continue to be strong. And in the U.S., the trend hasn't changed either when it comes to rheumatoid arthritis.

好的。非常感謝。讓我們從 COVID-19 中的 Oluminant 開始。如果你看一下 Olumiant 的第四季度表現，我認為你應該假設美國以外的類風濕關節炎和特應性皮炎的潛在業務繼續強勁。在美國，風濕性關節炎的趨勢也沒有改變。

In the U.S., a significant chunk of sales from Olumiant is coming from COVID-19 in Q4 and a minor chunk outside of the U.S. as well. It's really hard to predict the pandemic, but we expect to see continued sales from Olumiant also in 2022 for treating hospitalized patients with COVID-19. However, at an enterprise level, we don't foresee it to be material.

在美國，Olumiant 的很大一部分銷售額來自第四季度的 COVID-19，還有一小部分來自美國以外的地區。真的很難預測這種流行病，但我們預計 2022 年 Oluminant 也將繼續銷售，用於治療 COVID-19 住院患者。然而，在企業層面，我們認為它並不重要。

For your second question in terms of atopic dermatitis, let me first reinforce that we are very confident when it comes to the risk/benefit profile of Olumiant across all the indications approved and studied. And we conducted 8 Phase III studies for atopic dermatitis in U.S. and outside of the U.S. And those were conducted in patients -- moderate to severely ill patients suffering from atopic dermatitis in need of systemic treatment. And that's really where we believe Olumiant is bringing the biggest benefits to patients early on in the treatment paradigm while FDA currently has a position of saving Olumiant for the refractory patients, where we see the incremental value of Olumiant to be quite limited.

對於您關於特應性皮炎的第二個問題，我首先要強調的是，在所有批准和研究的適應症中，我們對 Olumiant 的風險/收益情況非常有信心。我們在美國和美國以外進行了 8 項針對特應性皮炎的 III 期研究，這些研究是在患者中進行的——需要全身治療的患有特應性皮炎的中度至重度患者。這就是我們認為 Olumiant 在治療範式早期為患者帶來最大好處的地方，而 FDA 目前的立場是為難治性患者保留 Olumiant，我們認為 Olumiant 的增量價值非常有限。

And if that doesn't change, it's likely that we will receive a complete response letter. And if so, we will continue to focus our efforts on the very successful launches that we have seen outside of the U.S. for atopic dermatitis as well as a very strong rheumatoid arthritis franchise with -- as well as preparing for, hopefully, an approval of alopecia areata in the U.S. and other markets later on this year.

如果這種情況沒有改變，我們很可能會收到一封完整的回复信。如果是這樣，我們將繼續專注於我們在美國以外看到的針對特應性皮炎的非常成功的上市，以及非常強大的類風濕性關節炎特許經營權——以及希望獲得批准的準備工作。斑禿將於今年晚些時候在美國和其他市場上市。

Moving on to mirikizumab. Yes, we had recently the readout of LUCENT-2 just prior to the end of last year. And we met the primary endpoint and all the secondary endpoints. And we didn't only achieve statistical significance but also clinically meaningful difference when it comes to clinical, symptomatic, histologic and endoscopic measures. And we have also conducted the first study ever with an IL-23p19 where we have demonstrated reduced bowel urgency, which we know is a major concern today for both clinicians but mainly for patients. So therefore, we are looking forward to submit mirikizumab for ulcerative colitis during the first half of this year and most likely become the first IL-23p19 in this very important space with a big unmet need and with a profile that we believe is very competitive versus both currently approved medicines and other biologics and JAKs in development.

繼續使用mirikizumab。是的，我們最近在去年年底之前讀取了 LUCENT-2。我們達到了主要終點和所有次要終點。在臨床、症狀、組織學和內窺鏡測量方面，我們不僅取得了統計學意義，而且還取得了具有臨床意義的差異。我們還進行了首次使用 IL-23p19 的研究，其中我們證明了腸道緊迫性降低，我們知道這是當今臨床醫生但主要是患者關注的主要問題。因此，我們期待在今年上半年提交用於治療潰瘍性結腸炎的 mirikizumab，並且很可能成為這個非常重要的領域中的第一個 IL-23p19，具有很大的未滿足需求，並且我們認為與該領域相比具有很強的競爭力目前批准的藥物和其他生物製劑和 JAK 正在開發中。

Thanks, Patrik. Kerry, thanks for your questions.

謝謝，帕特里克。克里，謝謝你的提問。

The next caller is Chris Shibutani with Goldman Sachs.

下一位來電者是高盛的 Chris Shibutani。

A question about the timeline plans for filing for dmab. It's been an arena of influence from different parties, the agency, CMS, where it appears as if there is sort of instruction that have breadth of scope across multiple different a-beta antibodies. So would you say that since we know that competitor data is upcoming for additional approaches later this year, does that impact your view on your approach and timing for filing dmab?

關於提交 dmab 的時間表計劃的問題。這是一個來自不同方、機構、CMS 的影響力舞台，似乎有某種指令在多種不同的 a-beta 抗體中具有廣泛的範圍。那麼您是否會說，由於我們知道今年晚些時候將提供其他方法的競爭對手數據，這是否會影響您對提交 dmab 的方法和時間的看法？

And then a second question would be on tirzepatide, the anticipated transition in type 2 diabetes. Trulicity has been very strong. But can you perhaps give us a better sense about how you expect that transition to play out? I think broadly, there's confidence in the profile that tirzepatide eventually will succeed in continuing the franchise position in type 2 diabetes. But would you expect for the initial tirzepatide launch to come primarily and importantly from the incidence population? Or will there be patient switching? A little insight into how that actual transition could play out in your view would be helpful.

然後第二個問題是關於 tirzepatide，這是 2 型糖尿病的預期轉變。真實性非常強。但是，您能否讓我們更好地了解您希望這種過渡如何進行？從廣義上講，我相信 tirzepatide 最終將成功地繼續在 2 型糖尿病領域的特許經營地位。但是您是否期望最初的 tirzepatide 推出主要且重要的是來自發病人群？還是會有病人轉換？深入了解實際過渡如何在您的視圖中發揮作用會有所幫助。

Thanks, Chris. We'll go to Dan for the question around donanemab filing timelines and then Mike for the transition with Trulicity and tirzepatide franchises.

謝謝，克里斯。我們將向 Dan 詢問有關 donanemab 提交時間表的問題，然後向 Mike 詢問 Trulicity 和 tirzepatide 特許經營權的過渡。

Thanks, Chris. You raised a good point with competitor readouts for amyloid-lowering drugs coming yet this year. We have to take into account expectations for those readouts. I think from our perspective, those readouts could be challenging.

謝謝，克里斯。你提出了一個很好的觀點，即今年即將推出的降低澱粉樣蛋白藥物的競爭對手讀數。我們必須考慮對這些讀數的期望。我認為從我們的角度來看，這些讀數可能具有挑戰性。

Obviously, we designed donanemab as a molecule -- our dosing strategy, our clinical trial strategy, including who we enrolled and what endpoints we look at, in order to maximize the ability to see a positive signal. Other trials haven't done that. So therefore, it's obvious that we would think that those trials should have lower probability of success.

顯然，我們將 donanemab 設計為一種分子——我們的給藥策略、我們的臨床試驗策略，包括我們招募的對象和我們觀察的終點，以最大限度地提高看到積極信號的能力。其他試驗沒有這樣做。因此，很明顯我們會認為這些試驗的成功概率應該更低。

I think if those trials are not successful, competitor readouts fail either because CDR Sum of Boxes is just too noisy an endpoint and that can go both ways, it could help or it could hurt, we saw that in the 2 aducanumab readouts; or because they have too many patients who are outside the optimal window of tau pathology because they're not doing that; or because they lower plaques too slowly. If any of those turn out to be correct and those trials turn out to be negative, I think that could further solidify CMS's reluctance to reimburse these drugs under accelerated approval.

我認為，如果這些試驗不成功，競爭對手的讀數要么失敗，要么因為 CDR Sum of Boxes 的端點噪音太大，而且這可能是雙向的，它可能有幫助，也可能會傷害，我們在 2 個 aducanumab 讀數中看到了這一點；或者因為他們有太多的患者不在 tau 病理學的最佳窗口之外，因為他們沒有這樣做；或者因為它們降低斑塊的速度太慢。如果其中任何一個結果是正確的並且這些試驗結果是否定的，我認為這可能會進一步鞏固 CMS 在加速批准下報銷這些藥物的意願。

It doesn't really fundamentally change our thinking though. As I said before, the key event for us is readout of our Phase III study. I think we've optimized everything for our chances of success. And regardless of competitor readouts, if we have a positive Phase III readout on top of our already first positive randomized controlled trial in TRAILBLAZER 1, that is a very good position for donanemab, and our expectation is that's a drug that will become globally available to patients and highly used by patients.

但它並沒有真正從根本上改變我們的想法。正如我之前所說，對我們來說，關鍵事件是我們的 III 期研究的宣讀。我認為我們已經為成功的機會優化了一切。不管競爭對手的讀數如何，如果我們在 TRAILBLAZER 1 中已經是第一個陽性隨機對照試驗的基礎上獲得陽性 III 期讀數，這對多納奈馬來說是一個非常好的位置，我們的期望是這種藥物將成為全球可用的藥物患者和患者高度使用。

Thanks, Dan. Mike?

謝謝，丹。麥克風？

Yes. Thanks for the question on Trulicity and tirzepatide. We're blessed to have both products. We're going to be taking -- again, from a long-term perspective on tirzepatide and Trulicity, our goal is to continue to grow the market in type 2 diabetes and then really expand the incretin class into the obesity market. Within type 2 diabetes, our goal not only is to expand the market but continue to expand our share of market within the incretin market.

是的。感謝關於 Trulicity 和 tirzepatide 的問題。我們很幸運擁有這兩種產品。我們將再次採取——再次，從 tirzepatide 和 Trulicity 的長期角度來看，我們的目標是繼續擴大 2 型糖尿病市場，然後真正將腸促胰島素類擴大到肥胖市場。在 2 型糖尿病中，我們的目標不僅是擴大市場，而且繼續擴大我們在腸促胰島素市場中的市場份額。

When you look at the way we promote our products, we take a very patient-centric approach to identifying those patients who could best benefit from a product like tirzepatide. In our market research, as we put the profile of tirzepatide up against 16 therapies, including Trulicity, both payers and health care professionals and people who live with diabetes see the superior profile of tirzepatide when you compare that to Trulicity, our Phase III trials that showed greater weight loss, better A1c control. And it's an exact same device as Trulicity. So there is obviously interest in the product, and they do see it as a superior product from Trulicity.

當您查看我們推廣產品的方式時，我們會採用非常以患者為中心的方法來確定那些最能從 tirzepatide 等產品中受益的患者。在我們的市場研究中，當我們將 tirzepatide 的概況與包括 Trulicity 在內的 16 種療法進行比較時，當您將其與 Trulicity 進行比較時，付款人和醫療保健專業人員以及糖尿病患者都會看到 tirzepatide 的優越概況，我們的 III 期試驗表明顯示出更大的體重減輕，更好的 A1c 控制。它是與 Trulicity 完全相同的設備。因此，人們顯然對該產品感興趣，他們確實將其視為 Trulicity 的優質產品。

Now what will -- what I believe will happen is that we will grow our overall share and you'll get a portion of patients who may have gone on Trulicity or may be on Trulicity and maybe out of control who needs greater weight loss or greater A1c control and those patients will go on tirzepatide. So we do anticipate that there will be some conversion from Trulicity over to tirzepatide, but our focus is really going to be making sure that we grow the overall class and grow the overall share of market for the Lilly incretin franchise.

現在會發生什麼 - 我相信將會發生的是，我們將增加我們的整體份額，並且您將獲得一部分可能已經使用 Trulicity 或可能正在使用 Trulicity 並且可能失控的患者，他們需要更大的減肥或更大的體重A1c 控制和那些患者將繼續使用 tirzepatide。因此，我們確實預計會有一些從 Trulicity 轉變為 tirzepatide 的轉變，但我們的重點確實是確保我們擴大整體類別並增加 Lilly incretin 特許經營權的整體市場份額。

We don't think it's appropriate to necessarily promote conversion of products. We are doing well on Trulicity, so it's not going to be a kind of internally focused conversion strategy. It's going to be very much a patient-focused product. For those patients who are out of control or need additional weight loss, tirzepatide can offer that. So we're quite excited about the opportunity to have 2 incretins in our portfolio and grow the overall class. Thank you for the question.

我們認為一定要促進產品的轉換是不合適的。我們在 Trulicity 上做得很好，所以它不會成為一種以內部為中心的轉換策略。這將是一個非常以患者為中心的產品。對於那些失控或需要額外減肥的患者，替西帕肽可以提供。因此，我們很高興有機會在我們的產品組合中擁有 2 個腸促胰島素並發展整個班級。感謝你的提問。

Thanks, Mike. Chris, thanks for your questions.

謝謝，邁克。克里斯，謝謝你的提問。

The next caller is Evan Seigerman from BMO.

下一位來電者是 BMO 的 Evan Seigerman。

All right. Well, if Evan is not there, we -- the queue's exhausted. We'll go to Dave for the close.

好的。好吧，如果 Evan 不在，我們 - 隊列已經用完了。我們將去戴夫為結束。

Okay. Thank you, Kevin. We appreciate everyone's participation in today's earnings call and of course, your interest in our company.

好的。謝謝你，凱文。我們感謝大家參加今天的財報電話會議，當然也感謝您對我們公司的興趣。

2021 was an incredible year for the company as we produced strong financial results and delivered important pipeline progress in each of our core therapeutic areas on behalf of the patients who rely on us. We entered 2022 with positive momentum and great focus on execution to deliver on the meaningful opportunities we have ahead of us.

2021 年對公司來說是令人難以置信的一年，因為我們代表依賴我們的患者在每個核心治療領域取得了強勁的財務業績並取得了重要的管道進展。我們以積極的勢頭進入 2022 年，並非常注重執行，以提供擺在我們面前的有意義的機會。

So thanks for dialing in today, and please follow up with our IR team if you have questions we have not addressed on the call. Have a good one. Take care.

因此，感謝您今天撥入電話，如果您有我們未在電話中解決的問題，請與我們的 IR 團隊聯繫。祝你有個好的一天。小心。