禮來公司 (LLY) 2022 Q4 法說會逐字稿

Ladies and gentlemen, thank you for standing by, and welcome to the Lilly Q4 2022 Earnings Conference Call. (Operator Instructions)

女士們，先生們，感謝你們的支持，歡迎來到禮來 2022 年第四季度收益電話會議。 （操作員說明）

And as a reminder, today's conference is being recorded. I would now like to turn the conference over to our host, Joe Fletcher, Senior Vice President of Investor Relations. Please go ahead.

提醒一下，今天的會議正在錄製中。我現在想把會議轉交給我們的主持人，投資者關係高級副總裁喬弗萊徹。請繼續。

Thank you, Lois. Good morning, and thank you all for joining us for Eli Lilly and Company's Q4 2022 Earnings Call. I'm Joe Fletcher. And joining me on today's call are Dave Ricks, Lilly's Chair and CEO; Anat Ashkenazi, Chief Financial Officer; Dr. Dan Skovronsky, Chief Scientific and Medical Officer; Anne White, President of Lilly Neuroscience; Ilya Yuffa, President of Lilly International; Jake Van Naarden, CEO of Loxo@Lilly; Mike Mason, President of Lilly Diabetes; and Patrik Jonsson, President of Lilly Immunology and Lilly USA. We're also joined by Mike Sprengnether, Kento Ueha and Lauren Zierke from the Investor Relations team.

謝謝你，洛伊絲。早上好，感謝大家參加禮來公司 2022 年第四季度財報電話會議。我是喬·弗萊徹。和我一起參加今天電話會議的還有禮來公司的董事長兼首席執行官 Dave Ricks； Anat Ashkenazi，首席財務官； Dan Skovronsky 博士，首席科學和醫學官；安妮懷特，禮來神經科學總裁；禮來國際總裁 Ilya Yuffa； Loxo@Lilly 首席執行官 Jake Van Naarden； Mike Mason，禮來糖尿病總裁；禮來免疫學和禮來美國總裁 Patrik Jonsson。投資者關係團隊的 Mike Sprengnether、Kento Ueha 和 Lauren Zierke 也加入了我們的行列。

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

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

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

我們提供的有關我們產品和管道的信息是為了投資界的利益。它不是為了促銷，也不足以規定決策。當我們過渡到準備好的評論時，請注意我們的評論將側重於非 GAAP 財務措施。

And now I'll turn the call over to Dave.

現在我會把電話轉給戴夫。

Okay. Thanks, Joe. 2022 is a year of strong pipeline and commercial performance for Lilly. We delivered top and bottom line growth in 2022 despite the impact of the Alimta LOE in the U.S. and significant FX headwinds, and delivered another remarkable year of pipeline progress. We began 2023 with multiple updates to our late-stage pipeline.

好的。謝謝，喬。 2022 年是禮來（Lilly）公司管道和商業業績強勁的一年。儘管受到美國 Alimta LOE 的影響和重大的外匯逆風，我們在 2022 年實現了收入和利潤增長，並取得了又一個顯著的管道進展年。我們從 2023 年開始對後期管道進行了多次更新。

In our Q2 2022 earnings call last August, we announced the filing of submissions for 2 assets with the FDA under an accelerated approval pathway: pirtobrutinib in mantle cell lymphoma; and donanemab in early symptomatic Alzheimer's disease. Last month, we received response from the FDA on both these assets.

在我們去年 8 月的 2022 年第二季度財報電話會議上，我們宣布通過加速審批途徑向 FDA 提交兩項資產的申請：用於套細胞淋巴瘤的吡妥布替尼；和多納單抗治療早期症狀性阿爾茨海默病。上個月，我們收到了 FDA 對這兩項資產的回應。

On January 19, we announced that the FDA issued a complete response letter for accelerated approval of donanemab due to the limited number of patients with at least 12 months of drug exposure. There were no other deficiencies cited. We will continue to work with the FDA to evaluate the best pathway to make this potential treatment option available to patients, and look forward to results next quarter for the TRAILBLAZER-ALZ 2 Phase III confirmatory trial, which will form the basis of donanemab's application for traditional approval.

1月19日，我們宣布，由於藥物暴露至少12個月的患者數量有限，FDA發布了加速批准donanemab的完整回复函。沒有提到其他缺陷。我們將繼續與 FDA 合作，評估為患者提供這種潛在治療選擇的最佳途徑，並期待下個季度 TRAILBLAZER-ALZ 2 III 期驗證試驗的結果，這將構成 donanemab 申請的基礎傳統的認可。

We have consistently stated that we would expect very limited uptake before CMS supports coverage. At the time we submitted for accelerated approval, we had hoped that there would be more movement from CMS to provide access to these medicines for people with Alzheimer's disease.

我們一直表示，在 CMS 支持覆蓋範圍之前，我們預計吸收率非常有限。在我們提交加速審批時，我們曾希望 CMS 能採取更多行動，為阿爾茨海默病患者提供這些藥物。

Unfortunately, this has not yet materialized. We maintain conviction that given the impact of this devastating disease and significant unmet need, positive confirmatory data and FDA traditional approval should be sufficient to support global reimbursement and patient access necessary for broad use of donanemab over time.

不幸的是，這還沒有實現。我們堅信，鑑於這種毀滅性疾病的影響和重大未滿足的需求，積極的確認數據和 FDA 的傳統批准應該足以支持全球報銷和患者獲得隨著時間的推移廣泛使用 donanemab 所必需的。

Also in the month of January, we received FDA approval for Jaypirca, the first and only non-covalent BTK inhibitor for adults with relapsed or refractory mantle cell lymphoma after at least 2 lines of systemic therapy, including a BTK inhibitor. Jaypirca is a highly selective kinase inhibitor, whose novel, reversible binding mechanism and pharmacology may allow for extended targeting of the BTK pathway following treatment with a covalent BTK inhibitor.

同樣在 1 月份，我們獲得了 FDA 對 Jaypirca 的批准，Jaypirca 是第一個也是唯一一個非共價 BTK 抑製劑，用於在至少 2 線全身治療（包括 BTK 抑製劑）後患有復發或難治性套細胞淋巴瘤的成人。 Jaypirca 是一種高選擇性激酶抑製劑，其新穎、可逆的結合機制和藥理學可能允許在用共價 BTK 抑製劑治療後擴展靶向 BTK 通路。

We are pleased with the recent approval of Jaypirca, and we remain confident in the long-term opportunity for donanemab. We also look forward to the potential launch of 2 of our immunology assets later this year with mirikizumab and lebrikizumab and of tirzepatide for obesity. This current wave of new launches, along with the ongoing focus and progress in our next wave of R&D innovation, underpins our long-term outlook to drive top-tier revenue growth and expand our margins over time.

我們對 Jaypirca 最近的批准感到高興，我們對 donanemab 的長期機會充滿信心。我們還期待今年晚些時候可能推出我們的 2 項免疫學資產，包括 mirikizumab 和 lebrikizumab 以及用於肥胖的 tirzepatide。當前的這一波新產品發布，以及我們下一波研發創新的持續關注和進展，鞏固了我們推動頂級收入增長並隨著時間的推移擴大利潤率的長期前景。

On Slide 4, you can see the progress we've made on our strategic deliverables. Excluding revenue from COVID-19 antibodies, revenue on a constant currency basis grew 10% in Q4 and 5% for the full year. Volume in our core business, again, excluding COVID-19 antibodies, grew 13% in Q4 and 12% for the year. This volume-driven performance was attributed to our key growth products, which grew 21% last quarter.

在幻燈片 4 上，您可以看到我們在戰略交付方面取得的進展。不包括來自 COVID-19抗體的收入，按固定匯率計算的收入在第四季度增長了 10%，全年增長了 5%。同樣，不包括 COVID-19 抗體在內，我們核心業務的銷量在第四季度增長了 13%，全年增長了 12%。這種以銷量為導向的業績歸功於我們的主要增長產品，上個季度增長了 21%。

For pipeline milestones, in addition to the recent FDA approval of Jaypirca, we have shared several important updates since our Q3 earnings call. Positive Phase III readout and FDA and EMA acceptance of the regulatory submission for Jardiance for adults with chronic kidney disease, the initiation of a rolling submission in the U.S. for tirzepatide in obesity, and FDA granting a Fast Track designation for tirzepatide in obstructive sleep apnea.

對於管道里程碑，除了最近 FDA 批准 Jaypirca 之外，我們還分享了自第三季度財報電話會議以來的幾個重要更新。陽性 III 期讀數以及 FDA 和 EMA 接受了針對患有慢性腎病的成年人的 Jardiance 的監管提交，在美國啟動了 tirzepatide 治療肥胖症的滾動提交，以及 FDA 授予 tirzepatide 治療阻塞性睡眠呼吸暫停的快速通道指定。

We also continue to put our cash flow to work to create long-term value. In late January, we announced plans to invest an additional $450 million for expansion of our Research Triangle Park manufacturing site in North Carolina to further augment our manufacturing capacity for the years ahead. On the business development front, we closed the acquisition of Akouos to expand our gene therapy capability, and we entered into a strategic research collaborations, with a focus on new modalities and technologies.

我們還繼續將現金流用於創造長期價值。 1 月下旬，我們宣布計劃追加投資 4.5 億美元用於擴建我們位於北卡羅來納州的 Research Triangle Park 製造基地，以進一步提高我們未來幾年的製造能力。在業務發展方面，我們完成了對 Akouos 的收購以擴大我們的基因治療能力，並且我們進行了戰略研究合作，重點是新模式和技術。

Finally, we continue to return capital to investors. In Q4, we distributed nearly $900 million to shareholders via the dividend, and we announced a 15% increase to the dividend for the fifth consecutive year.

最後，我們繼續向投資者返還資金。在第四季度，我們通過股息向股東分配了近 9 億美元，我們宣布連續第五年將股息增加 15%。

Moving to Slide 5. You'll see a list of the key events since our Q3 earnings call, including several important regulatory, clinical, business development and ESG updates we are discussing today or that were discussed during our guidance call on December 13.

轉到幻燈片 5。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，包括我們今天正在討論或在 12 月 13 日的指導電話會議上討論的幾項重要的監管、臨床、業務發展和 ESG 更新。

One item I'd like to highlight is the collaboration we announced in December with EVA Pharma to deliver a sustainable supply of affordable, high-quality insulin to at least 1 million people living with diabetes in low- to middle-income countries, most of which are in Africa. This is an important collaboration with a local company to produce low quality -- or low-cost, high-quality medicines, sorry. Strengthening capacity and building self-reliance for insulin manufacturing within the African region will provide a more sustainable supply in the long term.

我想強調的一個項目是我們在 12 月宣布與 EVA Pharma 的合作，為中低收入國家的至少 100 萬糖尿病患者提供可持續供應的負擔得起的高質量胰島素，其中大部分在非洲。這是與當地公司的一項重要合作，旨在生產低質量——或低成本、高質量的藥物，抱歉。從長遠來看，加強非洲地區胰島素生產能力和建立自力更生能力將提供更可持續的供應。

With this agreement, Lilly will sell insulin API to EVA Pharma at a significantly reduced price and provide pro bono technology transfer to enable EVA to formulate, fill and finish insulin vials and cartridges. We're proud to be a part of this novel arrangement, which aligns with our 30x30 goal of improving access to quality health care for 30 million people living in limited resource settings annually by 2030.

根據該協議，禮來將以大幅降低的價格向 EVA Pharma 出售胰島素 API，並提供無償技術轉讓，使 EVA 能夠配製、灌裝和完成胰島素小瓶和藥筒。我們很自豪能夠成為這一新穎安排的一部分，它符合我們的 30x30 目標，即到 2030 年每年為生活在資源有限環境中的 3000 萬人改善獲得優質醫療保健的機會。

Now I'll turn the call over to Anat to review our Q4 and full year 2022 results.

現在我將電話轉給 Anat，以審查我們的第四季度和 2022 年全年業績。

Thanks, Dave. Slides 6 and 7 summarize financial performance in the fourth quarter and full year 2022. I'll focus my comments on non-GAAP performance.

謝謝，戴夫。幻燈片 6 和 7 總結了第四季度和 2022 年全年的財務業績。我將重點關注非 GAAP 業績。

As Dave mentioned, we're pleased to report 10% growth for our core business in Q4 on a constant currency basis, driven by strong volume growth. A couple of notable items affected year-over-year comparisons. The first is COVID-19 antibody revenue in Q4 2022, which compared to the prior year, declined 96% from approximately $1.1 billion in Q4 2021 to $38 million in Q4 2022.

正如 Dave 所提到的，我們很高興地報告，在強勁的銷量增長的推動下，我們的核心業務在第四季度以固定匯率計算增長了 10%。一些值得注意的項目影響了同比比較。首先是 2022 年第四季度的 COVID-19 抗體收入，與上一年相比下降了 96%，從 2021 年第四季度的約 11 億美元降至 2022 年第四季度的 3800 萬美元。

Bebtelovimab is currently not authorized for emergency use in any U.S. region, and we continue to expect no COVID-19 antibody revenue for 2023. Second is the continued foreign exchange headwinds compared to 2021, which resulted in a 415 basis points dampening of revenue growth in Q4.

Bebtelovimab 目前未獲准在美國任何地區緊急使用，我們繼續預計 2023 年不會有 COVID-19 抗體收入。其次是與 2021 年相比持續的外匯逆風，這導致 415 個基點的收入增長受到抑制Q4.

Key growth products grew by 21% and accounted for 70% of our revenue this quarter. For the full year 2022, revenue excluding revenue from COVID-19 antibodies, grew 2% or 5% on a constant currency basis. Our non-GAAP gross margin was 80.5% in Q4, an increase of approximately 440 basis points, primarily driven by lower sales of COVID-19 antibodies, partially offset by lower realized price and increased expenses due to inflation and logistics costs.

主要增長產品增長了 21%，佔本季度收入的 70%。在 2022 年全年，不包括 COVID-19抗體收入在內的收入按固定匯率計算增長了 2% 或 5%。我們第四季度的非美國通用會計準則毛利率為 80.5%，增加了約 440 個基點，這主要是由於 COVID-19 抗體的銷售額下降，部分被實現價格下降以及通貨膨脹和物流成本導致的費用增加所抵消。

Total operating expenses declined 1% in Q4. Lower acquired IPR&D and development milestone charges were largely offset by higher marketing, selling and administrative expenses and higher R&D expenses. Marketing, selling and administrative expenses increased 3% in Q4, primarily driven by costs supporting the launch of new products and indications, partially offset by the favorable impact of foreign exchange rates. R&D expense for the quarter increased 5%, driven by higher development expenses for late-stage assets, partially offset by favorable impact of foreign exchange rates.

第四季度總運營費用下降了 1%。較低的收購 IPR&D 和開發里程碑費用在很大程度上被較高的營銷、銷售和管理費用以及較高的研發費用所抵消。營銷、銷售和管理費用在第四季度增長了 3%，這主要是受支持新產品和適應症推出的成本推動，部分被匯率的有利影響所抵消。本季度研發費用增長 5%，主要受後期資產開發費用增加的推動，部分被匯率的有利影響所抵消。

Operating income declined 7% compared to Q4 2021 driven by lower revenue, partially offset by lower operating expenses. Operating margin for Q4 was 27.4%, which includes a negative impact of approximately 330 basis points attributed to acquired IPR&D and development milestone charges. Full year operating margin was 27.8%, an increase from 26.8% in 2021.

與 2021 年第四季度相比，營業收入下降了 7%，原因是收入減少，部分被營業費用減少所抵消。第 4 季度的營業利潤率為 27.4%，其中包括約 330 個基點的負面影響，歸因於收購的 IPR&D 和開發里程碑費用。全年營業利潤率為 27.8%，高於 2021 年的 26.8%。

Our Q4 effective tax rate was 7.3%, bringing our full year 2022 effective tax rate to 10.3%. As we shared during our guidance call in December, we had assumed that the 2017 Tax Act provision requiring capitalization, amortization of research and development expenses for tax purposes would be deferred or repealed by Congress in late 2022. However, no legislative action was taken related to this provision, which resulted in a lower effective tax rate for 2022 versus the guidance range previously shared. In addition, this provision did increase our tax payment in 2022 by approximately $1.2 billion. At the bottom line, earnings per share declined 4% in Q4 and increased 7% for the full year.

我們第四季度的有效稅率為 7.3%，使我們 2022 年全年的有效稅率達到 10.3%。正如我們在 12 月的指導電話會議上分享的那樣，我們曾假設 2017 年稅法規定要求出於稅收目的對研發費用進行資本化、攤銷的規定將在 2022 年底被國會推遲或廢除。但是，沒有採取相關的立法行動該規定導致 2022 年的有效稅率低於之前共享的指導範圍。此外，這項規定確實使我們 2022 年的納稅額增加了約 12 億美元。最後，第四季度每股收益下降 4%，全年增長 7%。

On Slide 8, we quantify the effect of price, rate and volume on revenue growth across key geographies. This quarter, U.S. revenue declined 10%. Excluding revenue from COVID-19 antibodies, revenue grew 11% in the U.S. The swap volume-driven growth was led by Verzenio, Mounjaro and Jardiance. Net price was flat in the U.S. this quarter. For the full year, the net price decrease of 3% in the U.S. was in line with our expectation.

在幻燈片 8 中，我們量化了價格、費率和數量對主要地區收入增長的影響。本季度，美國收入下降了 10%。不包括來自 COVID-19抗體的收入，美國的收入增長了 11%。掉期交易量驅動的增長由 Verzenio 、 Mounjaro 和 Jardiance 引領。本季度美國的淨價持平。全年，美國淨價格下降 3%，符合我們的預期。

Moving to Europe. Revenue in Q4 increased 8% in constant currency, driven primarily by volume growth for Jardiance, Trulicity and Verzenio. We remain encouraged with the momentum of our business in Europe.

移居歐洲。按固定匯率計算，第四季度的收入增長了 8%，主要受 Jardiance 、 Trulicity 和 Verzenio 銷量增長的推動。我們對歐洲業務的發展勢頭感到鼓舞。

In Japan, revenue in Q4 decreased 6% in constant currency. Revenue growth in Japan continues to be negatively impacted, albeit less so than in prior quarters by decreased demand for several products that have lost patent exclusivity, including Alimta and Cymbalta. We expect to return to growth this year as we scale key products and launch Mounjaro.

在日本，按固定匯率計算，第四季度的收入下降了 6%。日本的收入增長繼續受到負面影響，儘管由於對包括 Alimta 和 Cymbalta 在內的幾種失去專利獨占性的產品的需求下降，影響程度低於前幾個季度。隨著我們擴展關鍵產品並推出 Mounjaro，我們預計今年將恢復增長。

In China, revenue grew 2% in constant currency as continued volume growth was mostly offset by lower realized prices for Humalog as a result of the volume-based procurement process and for products listed on the NRDL as well as by COVID-19 disruption.

在中國，收入按固定匯率計算增長了 2%，因為持續的銷量增長大部分被 Humalog 因基於數量的採購流程和 NRDL 上列出的產品的較低實現價格以及 COVID-19中斷所抵消。

Revenue in the rest of the world increased 11% in constant currency this quarter, driven by approximately $130 million of onetime revenue associated with the sale of the company's right to Alimta in Korea and Taiwan.

本季度世界其他地區的收入按固定匯率計算增長了 11%，這主要得益於與公司在韓國和台灣出售 Alimta 權利相關的一次性收入約 1.3 億美元。

As shown on Slide 9, our key growth products continue to drive robust worldwide volume growth, contributing 15 percentage points of volume growth this quarter. As mentioned previously, the decline in COVID-19 antibody volume was substantial in Q4 2022 and was largely offset -- and largely offset volume growth from key products. While we will face similar prior period headwinds from COVID-19 antibody revenue through the first 3 quarters of 2023, our long-term growth prospects are underpinned by our innovative pipeline and key growth products, including Mounjaro.

如幻燈片 9 所示，我們的主要增長產品繼續推動強勁的全球銷量增長，本季度貢獻了 15 個百分點的銷量增長。如前所述，2022 年第四季度 COVID-19 抗體數量的下降幅度很大，並且在很大程度上被抵消了——並且在很大程度上抵消了關鍵產品的數量增長。雖然我們將在 2023 年前三季度面臨 COVID-19抗體收入帶來的類似前期逆風，但我們的長期增長前景得到我們創新管道和主要增長產品（包括 Mounjaro）的支撐。

Slide 10 further highlights the contributions of our key growth products. This quarter, these brands grew 21% or 27% in constant currency, generated $5.1 billion in sales and made up 70% of our total revenue.

幻燈片 10 進一步突出了我們主要增長產品的貢獻。本季度，這些品牌按固定匯率計算增長了 21% 或 27%，產生了 51 億美元的銷售額，占我們總收入的 70%。

While Lilly's incretin portfolio understandably generates high interest, we continue to see tremendous growth, both in percentage and absolute terms for other key products, including Verzenio and Jardiance. Verzenio sales in the quarter grew 100%, driven mainly by the edge of an indication. Jardiance sales grew 42%, and the product retains the leadership position in a competitive market globally. Demand for our incretin portfolio remains strong, both for Trulicity globally and Mounjaro in the U.S., and we remain focused on bringing additional capacity online to meet this robust demand in upcoming launches.

雖然禮來（Lilly）的腸降血糖素產品組合產生了很高的興趣，這是可以理解的，但我們繼續看到其他主要產品（包括 Verzenio 和 Jardiance）在百分比和絕對值方面的巨大增長。本季度 Verzenio 的銷售額增長了 100%，主要受適應症邊緣的推動。 Jardiance 銷售額增長了 42%，該產品在全球競爭激烈的市場中保持領先地位。對我們的腸促胰島素產品組合的需求依然強勁，無論是全球的 Trulicity 還是美國的 Mounjaro，我們仍然專注於在線增加產能以滿足即將推出的這一強勁需求。

In terms of supply, as mentioned in our guidance call in December, given strong demand for incretin products, there have been intermittent delays at wholesalers and pharmacies in receiving certain doses levels of Mounjaro and Trulicity in the U.S. We continue to update the FDA on the situation, and the FDA has been posting to its website details regarding affected doses and expected timing. To meet this rapidly growing demand across our incretin business, we have announced plans to add additional substantial capacity in the years ahead. The most proximal of these efforts is our RTP side, North Carolina, where progress continues as planned, and we look forward to the start of production later this year.

在供應方面，正如我們在 12 月份的指導電話中提到的那樣，鑑於對腸促胰島素產品的強勁需求，批發商和藥店在美國接收某些劑量水平的 Mounjaro 和 Trulicity 時有間歇性延遲。我們繼續向 FDA 更新有關情況，FDA 已在其網站上發布有關受影響劑量和預期時間的詳細信息。為了滿足我們腸促胰島素業務快速增長的需求，我們已宣布計劃在未來幾年增加額外的大量產能。這些努力中最接近的是我們在北卡羅來納州的 RTP 方面，那裡的進展按計劃進行，我們期待今年晚些時候開始生產。

Moving to Slide 11. Mounjaro's strong launch uptake continues, underpinned by differentiated efficacy profile and positive customer experiences. For Q4, approximately 75% of Mounjaro's new therapy starts are patients new to the type 2 diabetes injectable incretin class, and further 10% of switches from Trulicity.

轉到幻燈片 11。Mounjaro 的強勁推出繼續受到差異化功效概況和積極客戶體驗的支持。對於第四季度，大約 75% 的 Mounjaro 新療法開始是 2 型糖尿病注射腸促胰島素類的新患者，還有 10% 的患者從 Trulicity 轉換。

As we mentioned in our Q3 earnings call in early November, we took actions in Q4 to reinforce the intended use of the Mounjaro savings program by type 2 diabetes patients. We indicated at that time that these actions could negatively impact new prescription volumes but were not expected to impact net revenue. As anticipated, we believe the new prescription volumes beginning in late November were impacted by these actions, with some week-by-week volatility driven by end-of-year seasonality. We continue to build payer access for Mounjaro for type 2 diabetes. As of January 1, access stands just over 50% for patients with type 2 diabetes across commercial and Part D.

正如我們在 11 月初的第三季度財報電話會議中提到的那樣，我們在第四季度採取了行動，以加強 2 型糖尿病患者對 Mounjaro 儲蓄計劃的預期使用。我們當時表示，這些行動可能會對新處方量產生負面影響，但預計不會影響淨收入。正如預期的那樣，我們認為從 11 月下旬開始的新處方量受到這些行動的影響，年末季節性因素導致每週出現一些波動。我們繼續為 Mounjaro 建立 2 型糖尿病的付款人通道。截至 1 月 1 日，商業和 D 部分的 2 型糖尿病患者的訪問率略高於 50%。

Regarding the percentage of paid scripts, for Q4, we estimate the percentage of paid script from Mounjaro to be approximately 40%, with paid script defined as dose prescription outside the 25 non-covered co-pay cards, but inclusive of the 25 covered co-pay cards. As we expand payer access, the proportion of paid scripts should continue to increase.

關於付費腳本的百分比，對於第 4 季度，我們估計來自 Mounjaro 的付費腳本百分比約為 40%，付費腳本定義為 25 種未覆蓋的共同支付卡之外的劑量處方，但包括 25 種覆蓋的共同支付卡-支付卡。隨著我們擴大付費訪問，付費腳本的比例應該會繼續增加。

On Slide 12, we provide an update on capital allocation. In 2022, we invested $9.6 billion to drive future growth through a combination of R&D expenditures, business development outlays and capital investment. In addition, we returned approximately $3.5 billion to shareholders in dividends and repurchased $1.5 billion in stock.

在幻燈片 12 上，我們提供了資本配置的最新信息。 2022 年，我們投資了 96 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未來增長。此外，我們還向股東返還了約 35 億美元的股息，並回購了 15 億美元的股票。

Our capital allocation priorities remain unchanged and are oriented towards achieving our strategic deliverables of top-tier revenue growth and speeding life-changing medicines to patients. We do this through investments in our current portfolio to drive new launches, investment in our manufacturing capacity, in our future innovation through R&D and business development. And we returned capital to shareholders through dividend payments and share repurchases.

我們的資本分配優先事項保持不變，旨在實現我們的頂級收入增長和加快為患者提供改變生命的藥物的戰略成果。我們通過投資我們當前的產品組合來推動新產品的發布、投資我們的製造能力、投資我們未來通過研發和業務發展的創新來做到這一點。我們通過股息支付和股票回購向股東返還資本。

Slide 13 provides an updated 2023 financial guidance. The only change we've made from the guidance we provided in December is to update our effective tax rate, which result in an updated EPS range. During December guidance call, we shared that the effective tax rate for 2023 would be approximately 16% based on the assumed deferral or repeal of the tax provision requiring capitalization of R&D. Since this provision was not deferred or repealed in 2022, and given the uncertainty around if and when such action will take place in 2023, we have updated our tax rate from 16% to approximately 13%. This update to our effective tax rate results in new EPS range of $7.90 to $8.10 on a GAAP basis and $8.35 to $8.55 on a non-GAAP basis.

幻燈片 13 提供了更新的 2023 年財務指南。我們對 12 月提供的指南所做的唯一更改是更新了我們的有效稅率，從而更新了 EPS 範圍。在 12 月的指導電話會議上，我們分享了 2023 年的有效稅率約為 16%，這是基於假設推遲或廢除需要研發資本化的稅收規定。由於這項規定在 2022 年沒有延期或廢除，並且考慮到 2023 年是否以及何時採取此類行動的不確定性，我們已將稅率從 16% 更新為大約 13%。我們對有效稅率的更新導致新的 EPS 範圍在 GAAP 基礎上為 7.90 美元至 8.10 美元，在非 GAAP 基礎上為 8.35 美元至 8.55 美元。

Regarding FX rates, there has been a general weakening of the dollar since we set our initial 2023 financial guidance last year. However, we're not adjusting guidance for FX changes at this time as we're only 1 month into the year, and FX markets can be quite volatile.

關於匯率，自我們去年設定 2023 年初步財務指引以來，美元普遍走弱。但是，我們目前不調整外匯變化的指導，因為我們今年才一個月，外匯市場可能會非常波動。

As I shared in December, the most significant headwind in revenue growth in 2023 versus 2022 will be the impact of COVID-19 antibody sales. This year-over-year comparisons will be most pronounced in Q1 2023, given that we had $1.5 billion of COVID-19 antibody sales in Q1 2022. To a lesser extent, the loss of exclusivity of Alimta in the U.S. in Q2 2022 will also impact year-over-year growth in the first half of 2023. Still the midpoint of our 2023 revenue guidance range represents roughly 7% of growth or 50% growth for our core business, excluding COVID-19 antibodies.

正如我在 12 月分享的那樣，與 2022 年相比，2023 年收入增長的最大阻力將是 COVID-19 抗體銷售的影響。鑑於我們在 2022 年第一季度的 COVID-19 抗體銷售額為 15 億美元，這種同比比較將在 2023 年第一季度最為明顯。在較小程度上，Alimta 在美國的排他性損失在 2022 年第二季度也將影響 2023 年上半年的同比增長。我們 2023 年收入指導範圍的中點仍然代表我們核心業務增長的大約 7% 或 50%，不包括 COVID-19抗體。

This year holds tremendous promise for us to help patients as we execute on the current wave of potential launches while maintaining our commitment to invest in and progress future innovation. We expect this ongoing focus on disciplined execution and investment will help drive top-tier revenue growth through at least 2030.

今年對我們來說有著巨大的希望，因為我們將在當前的潛在上市浪潮中執行，同時保持我們對投資和推進未來創新的承諾。我們預計，這種對嚴格執行和投資的持續關注將有助於至少在 2030 年之前推動頂級收入增長。

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

現在，我將把電話轉給丹，以提供我們管道的最新情況。

Thanks, Anat. 2022 was a really productive year for Lilly R&Ds. We advanced our late-stage assets of tirzepatide, donanemab, pirtobrutinib, mirikizumab and lebrikizumab to key regulatory submissions, and we obtained the approval for Mounjaro. We launched Mounjaro for type 2 diabetes in mid-2022. As Dave shared, we received an approval last week for pirtobrutinib, now known as Jaypirca. By the end of this year, we also have the potential to launch 2 new immunology assets with mirikizumab and lebrikizumab. And for donanemab, we're looking forward to our Phase III readout mid-year, which if positive, will form the basis of our submission for traditional approval.

謝謝，阿納特。 2022 年對於禮來研發來說是真正富有成效的一年。我們將 tirzepatide、donanemab、pirtobrutinib、mirikizumab 和 lebrikizumab 的後期資產推進到關鍵監管提交，並獲得了 Mounjaro 的批准。我們於 2022 年年中推出了用於治療 2 型糖尿病的 Mounjaro。正如 Dave 分享的那樣，我們上週獲得了 pirtobrutinib（現稱為 Jaypirca）的批准。到今年年底，我們還有可能推出 2 種新的免疫學資產，包括 mirikizumab 和 lebrikizumab。對於 donanemab，我們期待年中的 III 期讀數，如果結果是肯定的，將構成我們提交傳統批准的基礎。

In 2022, we also gained clarity on the next wave of assets that have entered or will soon enter Phase III registrational trials. Those are our SERD in breast cancer; our weekly insulin for diabetes; remternetug in Alzheimer's disease; and as shared in our December guidance call, we now have orforglipron and retatrutide in diabetes and obesity.

2022 年，我們還明確了下一波已經進入或即將進入 III 期註冊試驗的資產。這些是我們在乳腺癌中的 SERD；我們每週的糖尿病胰島素；阿爾茨海默病的再治療；正如我們在 12 月的指導電話會議中所分享的那樣，我們現在有用於治療糖尿病和肥胖症的奧福列隆和瑞他魯肽。

Given the updates we provided in mid-December, today, I'll just briefly highlight progress since our last earnings call. Slide 14 shows select pipeline opportunities as of January 30, and Slides 15 and 16 show a recap of 2022 key events and potential key events for 2023.

鑑於我們在 12 月中旬提供的更新，今天，我將簡要強調自上次財報電話會議以來取得的進展。幻燈片 14 顯示了截至 1 月 30 日的精選管道機會，幻燈片 15 和 16 顯示了 2022 年關鍵事件和 2023 年潛在關鍵事件的回顧。

Starting with diabetes and cardiometabolic disease. In November, we shared results from the EMPA-KIDNEY Phase III trial in collaboration with Boehringer Ingelheim. As the largest and broadest SGLT2 inhibitor trial in CKD to date, the results showed a significant benefit of Jardiance in reducing the relative risk of kidney disease progression or cardiovascular death by 28% compared with placebo in people with chronic kidney disease.

從糖尿病和心臟代謝疾病開始。 11 月，我們與勃林格殷格翰分享了 EMPA-KIDNEY III 期試驗的結果。作為迄今為止 CKD 中規模最大、範圍最廣的 SGLT2 抑製劑試驗，結果顯示，與安慰劑相比，Jardiance 在慢性腎病患者中顯著降低腎臟疾病進展或心血管死亡的相對風險 28%。

The overall safety data were consistent with previous findings, confirming the well-established safety profile of Jardiance. CKD is a leading cause of death worldwide, affecting over 850 million people globally and 37 million in the U.S. We've submitted to the FDA an EMA for approval, and expect to make submissions to other regulatory agencies in the coming months.

總體安全性數據與之前的研究結果一致，證實了 Jardiance 公認的安全性。 CKD 是全球死亡的主要原因，影響全球超過 8.5 億人和美國 3700 萬人。我們已經向 FDA 提交了 EMA 以供批准，並預計在未來幾個月內向其他監管機構提交。

In January, we started QWINT-1, a Phase III study comparing fixed-dose escalation of Lilly's weekly insulin to insulin glargine in insulin-naïve type 2 diabetes patients. With this initiation, all 5 studies in the QWINT Phase III program are now underway.

1 月，我們啟動了 QWINT-1，這是一項 III 期研究，比較禮來每週胰島素與甘精胰島素在未使用胰島素的 2 型糖尿病患者中的固定劑量升級。隨著這一啟動，QWINT III 期項目的所有 5 項研究現在都在進行中。

Moving to earlier-stage assets in our diabetes and CV pipeline. In Q4, we advanced 2 assets into Phase II that aim to lower Lp(a), a well-known risk factor for atherosclerotic cardiovascular disease. The first is an oral inhibitor, a small molecule that disrupts the interaction between the apo(a) protein and the lipoprotein particle; and the second uses siRNA to disrupt the production of apo(a) in the liver. We shared proof-of-concept data on the siRNA asset during our December 2021 R&D investor meeting. This is our second siRNA asset to advance to Phase II, following our ANGPTL3 siRNA, which entered Phase II earlier in 2022. We also recently moved an siRNA asset targeting apoC-III in cardiovascular disease into Phase I.

轉向我們糖尿病和 CV 管道中的早期資產。在第四季度，我們將 2 項資產推進到 II 期，旨在降低 Lp(a)，這是眾所周知的動脈粥樣硬化性心血管疾病的風險因素。第一種是口服抑製劑，一種破壞載脂蛋白 (a) 蛋白和脂蛋白顆粒之間相互作用的小分子；第二種使用 siRNA 破壞肝臟中 apo(a) 的產生。我們在 2021 年 12 月的研發投資者會議上分享了 siRNA 資產的概念驗證數據。這是繼我們的 ANGPTL3 siRNA 之後進入 II 期的第二個 siRNA 資產，後者於 2022 年初進入 II 期。我們最近還將針對心血管疾病中的 apoC-III 的 siRNA 資產轉移到 I 期。

Our genetic medicines portfolio is advancing, and we remain optimistic about the prospect of improving cardiovascular outcomes with these molecules. Lastly, we discontinued our Phase I KHK inhibitor.

我們的基因藥物組合正在推進，我們對使用這些分子改善心血管結果的前景保持樂觀。最後，我們停用了 I 期 KHK 抑製劑。

In oncology, we're, of course, pleased with the recent approval of Jaypirca, and we look forward to continuing the substantial ongoing development program for the molecule in the years ahead. Jaypirca is the second product approved from our 2019 Loxo Oncology acquisition, which reshaped our oncology efforts at Lilly. Loxo@Lilly's growing NME portfolio now includes a number of emerging assets shown in our pipeline, including our FGFR3 program, which recently dosed its first patient.

在腫瘤學方面，我們當然對 Jaypirca 最近的批准感到高興，我們期待著在未來幾年繼續為該分子進行大量正在進行的開發計劃。 Jaypirca 是我們 2019 年收購 Loxo Oncology 後批准的第二個產品，它重塑了我們在禮來（Lilly）的腫瘤學工作。 Loxo@Lilly 不斷增長的 NME 產品組合現在包括我們管道中顯示的許多新興資產，包括我們的 FGFR3 項目，該項目最近為第一位患者給藥。

Also, in Q4, we dosed the first patient in EMBER-4, our second Phase III trial for imlunestrant, our oral SERD. EMBER-4 will study imlunestrant in the adjuvant setting as a sequential monotherapy in patients who previously received 2 to 5 years of adjuvant endocrine therapy for ER-positive, HER2-negative early breast cancer with increased risk of recurrence.

此外，在第四季度，我們對 EMBER-4 中的第一位患者進行了給藥，這是我們針對 imlunestrant 的第二個 III 期試驗，即我們的口服 SERD。 EMBER-4 將在輔助環境中研究 imlunestrant 作為序貫單一療法，用於先前接受過 2 至 5 年輔助內分泌治療的 ER 陽性、HER2 陰性早期乳腺癌且複發風險增加的患者。

Lastly, turning to Verzenio. As noted in our guidance call, at the San Antonio Breast Cancer Symposium in December, we shared the latest interim analysis for monarchE, our adjuvant high-risk early breast cancer study of abemaciclib in combination with endocrine therapy for the treatment of adult patients with HR-positive, HER2-negative, node-positive early breast cancer at high risk of recurrence. We've now submitted an sNDA to the U.S. FDA to potentially expand our adjuvant indication beyond the currently indicated cohort 1 Ki-67 greater than 20% population.

最後，轉向 Verzenio。正如我們在 12 月的聖安東尼奧乳腺癌研討會上的指導電話中所指出的，我們分享了 monarchE 的最新中期分析，這是我們的 abemaciclib 輔助高危早期乳腺癌研究，聯合內分泌治療治療 HR 成年患者陽性、HER2 陰性、淋巴結陽性的早期乳腺癌復發風險高。我們現在已經向美國 FDA 提交了一份 sNDA，以潛在地擴大我們的輔助適應症，使其超出目前指定的隊列 1 Ki-67 超過 20% 的人群。

In immunology, we're looking forward to potential FDA approvals later this year for mirikizumab in ulcerative colitis, which we expect in the first half of the year and lebrikizumab in atopic dermatitis, which we expect in the second half of the year. Looking earlier in our immunology pipeline, as mentioned in our guidance call, we presented exciting proof-of-concept results for our PD-1 agonist antibody, peresolimab, in rheumatoid arthritis at the ACR conference in November, and we have now initiated a global dose-ranging Phase IIb study.

在免疫學方面，我們期待 FDA 可能在今年晚些時候批准用於潰瘍性結腸炎的 mirikizumab（我們預計在今年上半年）和用於特應性皮炎的 lebrikizumab（我們預計在下半年）。回顧我們的免疫學管道，正如我們的指導電話中提到的，我們在 11 月的 ACR 會議上展示了我們的 PD-1 激動劑抗體 peresolimab 在類風濕性關節炎中令人興奮的概念驗證結果，我們現在已經啟動了全球劑量範圍的 IIb 期研究。

Moving to neuroscience. We've advanced into Phase II our P2X7 inhibitor for chronic pain. Lilly acquired rights to this asset from Asahi Kasei Pharma in early 2021.

轉向神經科學。我們的 P2X7 慢性疼痛抑製劑已進入 II 期。禮來（Lilly）於 2021 年初從 Asahi Kasei Pharma 手中收購了該資產的權利。

With regards to donanemab. As Dave mentioned, the solid efficiency cited by the FDA to our submission for accelerated approval was the number of patients with at least 12 months of drug exposure. The Phase II TRAILBLAZER-ALZ trial, on which the accelerated approval application was based, allowed patients to complete their course of treatment with donanemab when they reached a predefined level of amyloid plaque clearance.

關於多納單抗。正如 Dave 所提到的，FDA 在我們提交的加速批准申請中引用的可靠效率是至少接觸藥物 12 個月的患者人數。加速批准申請所基於的 II 期 TRAILBLAZER-ALZ 試驗允許患者在達到預定的澱粉樣斑塊清除水平時完成多納單抗的治療過程。

Due to the speed of plaque reduction that we saw, many patients were able to stop dosing as early as 6 months into treatment, resulting in fewer patients receiving 12 months or more of donanemab dosing. We remain confident in the potential of donanemab as a new treatment for people with early symptomatic Alzheimer's disease, and look forward to sharing results from the Phase III TRAILBLAZER-ALZ 2 study in Q2 of this year.

由於我們看到的斑塊減少速度，許多患者能夠早在治療 6 個月後就停止給藥，從而減少了接受 12 個月或更長時間多納單抗給藥的患者。我們對 donanemab 作為早期症狀性阿爾茨海默病患者的新療法的潛力充滿信心，並期待在今年第二季度分享 III 期 TRAILBLAZER-ALZ 2 研究的結果。

In summary, while 2022 was an outstanding year of pipeline progress, we're fully focused on the work we need to do in 2023 to make our next set of potential medicines a reality for patients. We look forward to providing additional updates throughout the year.

總而言之，雖然 2022 年是管道進展出色的一年，但我們完全專注於我們在 2023 年需要做的工作，以使我們的下一組潛在藥物成為患者的現實。我們期待在全年提供更多更新。

Now I turn the call back to Dave.

現在我把電話轉回給戴夫。

Thanks, Dan. Before we move to Q&A, let me summarize the progress we made during 2022. We delivered strong revenue growth in our core business, propelled by our key growth products. We launched Mounjaro for patients with type 2 diabetes, while advancing and expanding our development program for tirzepatide, including the start of the SURMOUNT-MMO outcome study and the initiation of a rolling submission for chronic weight management. In 2022, we submitted regulatory applications for important pipeline products like mirikizumab, pirtobrutinib and lebrikizumab. And in 2023, we've already received approval for Jaypirca and are poised to advance donanemab in the regulatory process, assuming positive data from the TRAILBLAZER-ALZ 2 Phase III study. In addition, we continue to invest in our pipeline, our capacity, our capabilities and our people.

謝謝，丹。在我們進行問答之前，讓我總結一下我們在 2022 年取得的進展。在我們的主要增長產品的推動下，我們的核心業務實現了強勁的收入增長。我們為 2 型糖尿病患者推出了 Mounjaro，同時推進和擴大了我們的 tirzepatide 開發計劃，包括開始 SURMOUNT-MMO 結果研究和啟動慢性體重管理的滾動提交。 2022年，我們提交了mirikizumab、pirtobrutinib和lebrikizumab等重要管線產品的監管申請。到 2023 年，我們已經獲得了 Jaypirca 的批准，並準備在監管過程中推進 donanemab，假設 TRAILBLAZER-ALZ 2 III 期研究的積極數據。此外，我們繼續投資於我們的管道、我們的能力、我們的能力和我們的人員。

Finally, we returned $5 billion to shareholders via the dividend and share repurchases; and for the fifth consecutive year, announced a 15% dividend increase for 2023.

最後，我們通過股息和股票回購向股東返還了 50 億美元；並連續第五年宣布 2023 年的股息增加 15%。

With continued growth of Mounjaro and our key products, including Verzenio, Jardiance and Taltz, we expect our core business revenue to grow by mid-teens in 2023. We are energized by the launch opportunities before us this year, and know strong launch execution is key to our long-term success. Taken together, we believe that we are well positioned to deliver top-tier revenue growth through at least 2030, and to deliver on Lilly's mission to make life better for people around the world.

隨著 Mounjaro 和我們的主要產品（包括 Verzenio、Jardiance 和 Taltz）的持續增長，我們預計我們的核心業務收入將在 2023 年增長 15%。我們對今年擺在我們面前的發布機會充滿活力，並且知道強大的發布執行是我們長期成功的關鍵。綜上所述，我們相信我們有能力至少在 2030 年前實現頂級收入增長，並實現禮來（Lilly）的使命，讓世界各地的人們生活得更美好。

So now I'll turn it over to Joe to moderate the Q&A session.

所以現在我將把它交給 Joe 來主持問答環節。

Thanks, Dave. (Operator Instructions) We'll end the call at 11:15. Lois, please go ahead and provide the instructions for the Q&A session, and we're ready for the first caller.

謝謝，戴夫。 （操作員說明）我們將在 11:15 結束通話。 Lois，請繼續提供問答環節的說明，我們已準備好迎接第一個來電者。

(Operator Instructions)

（操作員說明）

Our first question is from Colin Bristow from UBS.

我們的第一個問題來自瑞銀的 Colin Bristow。

Just first on Mounjaro. So it looks like the net price dropped again from 3Q to 4Q. Can you just walk us through what specifically drove this? And just update us on how you expect this to trend over the course of the year.

就在 Mounjaro 上。所以看起來淨價從第三季度到第四季度再次下跌。你能告訴我們具體是什麼推動了這一切嗎？並向我們更新您對這一年趨勢的預期。

And then just maybe looking sort of out to the future of your obesity portfolio. Beyond GGG, do you have any interest in mechanisms that target the sort of the mitochondrial uncoupling side of the equation, that would be helpful.

然後可能會展望您肥胖組合的未來。除了 GGG，您是否對針對等式的線粒體解偶聯端的機制感興趣，這會有所幫助。

Thanks, Colin. We'll go to Mike for the first question on gross to net and price for Mounjaro and then hand over to Dan for kind of broader obesity mechanistic commentary. Mike?

謝謝，科林。我們將向 Mike 提出第一個關於 Mounjaro 的總淨值和價格的問題，然後交給 Dan 進行更廣泛的肥胖機制評論。麥克風？

Yes. Thanks for the question. I think the best way to answer that is to kind of take a look at what we saw as kind of our Mounjaro paid scripts in Q4 and then how we think that will progress over '23.

是的。謝謝你的問題。我認為回答這個問題的最好方法是看看我們在第四季度看到的 Mounjaro 付費腳本，然後我們認為這將如何在 23 年取得進展。

In the fourth quarter, we classified about 40% of Mounjaro scripts as paid, which we defined as patients that aren't supported by our $25 non-covered savings program.

在第四季度，我們將大約 40% 的 Mounjaro 腳本歸類為付費，我們將其定義為不受我們 25 美元非承保儲蓄計劃支持的患者。

In our savings program, as we discussed at launch, was designed to bridge people living with type 2 diabetes to access. As we discussed in the Q3 earnings call, we have adjusted a program to better ensure it's being used for people living only with type 2 diabetes. These adjustments included removing our $25 non-covered benefit from our savings card for new patients.

正如我們在發佈時所討論的那樣，在我們的儲蓄計劃中，旨在為 2 型糖尿病患者提供便利。正如我們在第三季度財報電話會議上討論的那樣，我們調整了一項計劃，以更好地確保它被用於僅患有 2 型糖尿病的人。這些調整包括從我們為新患者提供的儲蓄卡中刪除 25 美元的非承保福利。

We didn't make any adjustments for existing patients whose savings cards are set to expire on June of this year, June 30. As expected, these changes have reduced new patient start volume while increasing the percent of new patients with a history of diabetes treatments and the percent with formulary coverage.

我們沒有對儲蓄卡將於今年 6 月 30 日到期的現有患者進行任何調整。正如預期的那樣，這些變化減少了新患者的開始數量，同時增加了有糖尿病治療史的新患者的百分比以及處方覆蓋率的百分比。

I think the way I would look at our savings program right now for new patients is that we have graduated from the bridging program and now are kind of the type of savings program really focused on covered patients that you would do in kind of a normalized cycle of a product.

我認為我現在看待我們針對新患者的儲蓄計劃的方式是，我們已經從橋接計劃中畢業，現在是一種真正專注於受保患者的儲蓄計劃，您可以在正常化週期中進行一個產品。

So thus, we expect that Mounjaro's percent of paid scripts and the net revenue per script to increase through 2023 as we continue to increase access and grow new starts.

因此，我們預計 Mounjaro 的付費腳本百分比和每個腳本的淨收入將在 2023 年之前增加，因為我們將繼續增加訪問權限並增加新的開始。

We remain disciplined in our access discussions so we can maximize long-term value. From the start, our value -- our approach was to make sure that we capture value in the long term versus the short term, and we've remained very disciplined on that. We have just over 50% access for lives in Part D and commercial segments for people living with type 2 diabetes. We're very pleased where we're at on the access front and where the way our contracting has turned out at this point. So hopefully, that helps provide some color to our gross to net in Q4. Thanks.

我們在訪問討論中保持紀律，以便我們可以最大化長期價值。從一開始，我們的價值——我們的方法就是確保我們在長期而不是短期內獲得價值，我們在這方面一直非常自律。對於 2 型糖尿病患者，我們在 D 部分和商業部分的生活中有超過 50% 的訪問權限。我們很高興我們在訪問方面所處的位置以及我們的合同方式在這一點上的結果。所以希望這有助於為我們在第四季度的淨收入提供一些顏色。謝謝。

Thanks, Colin. For your question on future mechanisms for treating obesity, I can assure you, we're not done innovating on behalf of people with obesity. There's a lot we can still do. I think keep your eyes open for more to come from Lilly labs on incretin and related types of mechanisms, but also broadly interested in a variety of new non-incretin-based mechanisms.

謝謝，科林。對於你關於未來治療肥胖機制的問題，我可以向你保證，我們沒有完成代表肥胖患者的創新。我們仍然可以做很多事情。我想請睜大眼睛，看看 Lilly 實驗室在腸降血糖素和相關類型機制方面的更多成果，但也對各種新的非腸促胰島素機制廣泛感興趣。

You specifically asked about, one, mitochondrial uncoupling, but there are several others, I think, that also have promise for patients.

你特別詢問了，一個，線粒體解偶聯，但我認為還有其他幾個對患者也有希望的問題。

I just sort of put a note of caution, though, treating obesity, we need to have a very high bar for the types of medicines we develop, remembering that this is a chronic, often lifetime disease and a highly prevalent population. We need medicines that, first and foremost, are extremely safe and really highly well tolerated for patients. So that's what we're looking for in future mechanisms.

不過，我只是提醒大家注意，治療肥胖症，我們需要對我們開發的藥物類型有一個非常高的標準，記住這是一種慢性的、通常是終生的疾病，並且在人群中非常流行。我們需要的藥物首先是極其安全且對患者俱有高度耐受性。這就是我們在未來機制中尋找的。

The next question is from the line of Chris Schott from JPMorgan.

下一個問題來自摩根大通的 Chris Schott。

Just one follow-up on the last set of questions. Is it still reasonable to think about a net Mounjaro price that could be above that of Trulicity as we look out to 2024 or whenever you achieve kind of comparable payer access?

只是對最後一組問題的一個跟進。當我們展望 2024 年或每當您獲得類似的付款人訪問權限時，考慮 Mounjaro 的淨價格可能高於 Trulicity 的價格是否仍然合理？

And then my question was on donanemab. I know there wasn't a huge revenue opportunity tied to the accelerated approval. But I think you had talked about using that gap between accelerated approval and full approval to really ramp physician education and infrastructure, et cetera. How do you kind of manage through that now, I guess, where we're going to have maybe a full approval that could be occurring closer into a CMS decision? So just maybe elaborate a bit about what that means for donanemab over time.

然後我的問題是關於 donanemab。我知道加速審批並沒有帶來巨大的收入機會。但我認為你已經談到利用加速批准和完全批准之間的差距來真正提升醫生教育和基礎設施等。我猜，你現在是如何管理的，我們可能會在接近 CMS 決策時獲得完全批准？因此，也許可以詳細說明隨著時間的推移這對 donanemab 意味著什麼。

Thanks, Chris. All right. We'll go to Mike for the question about Mounjaro price kind of over time and how it might compare to Trulicity. And then to Anne on your donanemab question about activity that would occur to ramp up HCP education. Mike?

謝謝，克里斯。好的。我們將向 Mike 詢問有關 Mounjaro 價格隨時間變化的問題，以及它與 Trulicity 的比較情況。然後就你的 donanemab 問題向 Anne 提問，該問題是關於加強 HCP 教育的活動。麥克風？

Yes, thanks for the question. I can't get into [real specifics] about our net price for obvious reasons, but maybe I'll address the question this way.

是的，謝謝你的提問。出於顯而易見的原因，我無法詳細了解我們的淨價，但也許我會以這種方式解決這個問題。

I mean if you look at -- when we have - when we reach -- we think we'll reach broad access for Mounjaro and reach ultimately similar access levels that we have for Trulicity. There's nothing differently about how we'll promote or how we'll support patients on Mounjaro versus Trulicity. So at the end of the day, it will come down to our net price negotiations with payers. We believe that Mounjaro has a better profile. We invest a lot of innovation in there, and we do believe that it should have a better net price than Trulicity.

我的意思是，如果你看看——當我們有——當我們達到——我們認為我們將實現 Mounjaro 的廣泛訪問，並最終達到與 Trulicity 相似的訪問級別。我們將如何推廣或如何支持 Mounjaro 與 Trulicity 上的患者沒有什麼不同。因此，歸根結底，這將取決於我們與付款人的淨價談判。我們認為 Mounjaro 的形象更好。我們在那裡投入了大量的創新，我們相信它的淨價應該比 Trulicity 更好。

Thanks, Mike. Anne?

謝謝，邁克。安妮？

Yes. Thanks, Chris, for the question on physician education and readiness. So as you said, the accelerated approval is not going to provide access for the vast majority of patients, so it doesn't impact us in that way. And obviously, accelerated approval would have made it maybe a little bit easier to do some of the things that we wanted to do, but there's still a great deal that we can do -- actually have been doing to make sure that the health care system is ready for these medicines. So we begin working on that. Things such as developing the diagnostic ecosystem are incredibly important, making sure that there's better integrated Alzheimer's disease pathways to make sure that physicians can properly identify, refer, infuse these patients. So that's the area of focus right now.

是的。謝謝，克里斯，關於醫生教育和準備的問題。所以正如你所說，加速批准不會為絕大多數患者提供訪問權限，因此它不會以這種方式影響我們。顯然，加速批准可能會讓我們做一些我們想做的事情變得更容易一些，但我們仍然可以做很多事情——實際上一直在做，以確保醫療保健系統準備好這些藥物。所以我們開始著手解決這個問題。諸如開發診斷生態系統之類的事情非常重要，確保有更好的整合阿爾茨海默氏病途徑，以確保醫生能夠正確識別、轉診、輸注這些患者。這就是現在的重點領域。

Certainly, diagnostics are a key area of focus for Lilly. We've continued to expand our PET network to make sure that we're ready for patient diagnosis. And then as well, we continue to be committed to P-tau blood tests and intend to launch that this year. So many things going on that I think can make us very ready for traditional approval and making sure that people can access these medicines.

當然，診斷是 Lilly 關注的一個關鍵領域。我們繼續擴大我們的 PET 網絡，以確保我們為患者診斷做好準備。然後，我們繼續致力於 P-tau 血液檢測，並打算在今年推出。發生了這麼多事情，我認為可以讓我們為傳統批准做好充分準備，並確保人們能夠獲得這些藥物。

The next question is from Seamus Fernandez from Guggenheim.

下一個問題來自古根海姆的 Seamus Fernandez。

So Dan, I wanted to ask you if you could talk a little bit about where you see the oral GLP-1 space developing and how your product is likely to be positioned. A little bit of this, I think, is also what you think the unmet need is outside of where the sort of very robust weight loss that we see from Mounjaro is.

所以丹，我想問你是否可以談談你看到口服 GLP-1 空間在哪裡發展以及你的產品可能如何定位。我認為，其中一點也是您認為未滿足的需求超出了我們從 Mounjaro 看到的那種非常強勁的減肥效果。

And then just an add-on to that, how do you see the oral market developing in terms of other potential agonists? Is that something that Lilly is pursuing and hoping to further develop combinations there as well?

然後只是一個附加項，您如何看待口服市場在其他潛在激動劑方面的發展？這是禮來正在追求並希望在那裡進一步開發組合的東西嗎？

Thanks, Seamus. And we'll go to Dan on this question.

謝謝，西默斯。我們將就這個問題去找 Dan。

Yes. Thanks, Seamus. I'll get started. Maybe Mike wants to add on, on some of the marketplace questions. But clearly, obesity is a huge problem in the U.S. and around the world. I think 100 million Americans potentially with obesity and reaching 1 billion people around the world pretty soon. That's probably not a market that even all of the interested companies could address solely with injectables. So just given the scope of the problem around the world, we're going to need orals.

是的。謝謝，西默斯。我會開始的。也許 Mike 想補充一些市場問題。但顯然，肥胖在美國和世界各地都是一個大問題。我認為 1 億美國人可能患有肥胖症，並且很快就會達到全球 10 億人。這可能不是一個甚至所有感興趣的公司都可以僅通過注射劑來解決的市場。因此，鑑於這個問題在世界範圍內的範圍，我們將需要口頭表達。

Ultimately, it's our goal to have orals that can match the safety, tolerability and efficacy of injectables. I think our oral GLP-1 is our first attempt in this space and has really good prospects for meeting that initial goal. But then noting, of course, that the injectables are going to get better over time and the orals will catch up as well.

最終，我們的目標是讓口服藥物能夠與註射劑的安全性、耐受性和療效相媲美。我認為我們的口服 GLP-1 是我們在這個領域的第一次嘗試，並且有很好的前景來實現最初的目標。但當然要注意，隨著時間的推移，注射劑會變得更好，口服劑也會迎頭趕上。

The second part of your question was how do the orals catch up. And I think you're sort of alluding to an obvious issue, which is right now, our oral GLP-1 and other orals in the space are single mechanism, single incretin agonists. I think we've seen with great drugs like Trulicity and competitive products, what single agonist against GLP-1 can achieve. It's not as good, I think, as what can be achieved with dual agonism for tirzepatide or hopefully even triple agonism with GGG. And so you can bet we're working on oral solutions that can bring additional incretin activity to patients in a pill. Nothing ready to disclose today, but we're working hard.

你問題的第二部分是口頭如何趕上。我認為你是在暗示一個明顯的問題，那就是現在，我們的口服 GLP-1 和該領域的其他口服藥物是單一機制，單一腸促胰島素激動劑。我認為我們已經看到像 Trulicity 這樣的優秀藥物和競爭產品，單一的 GLP-1 激動劑可以達到什麼效果。我認為，它不如 tirzepatide 的雙重激動或 GGG 的三重激動所能達到的效果好。因此，您可以打賭，我們正在研究口服溶液，可以通過藥片為患者帶來額外的腸促胰島素活性。今天沒有什麼可以透露的，但我們正在努力工作。

Next question is from the line of Geoff Meacham from Bank of America.

下一個問題來自美國銀行的 Geoff Meacham。

I have two related ones on tirzepatide. Dan, I know you have SURMOUNT-4 coming up, which is the maintenance study, but how has your thinking evolved, if at all, on the potential duration of tirzepatide use, either based on longer exposure from clinical studies or in the real world? And do you think that could inform payer discussions?

我有兩個關於 tirzepatide 的相關藥物。 Dan，我知道您即將進行 SURMOUNT-4，這是維持研究，但是您的想法是如何演變的，如果有的話，基於臨床研究或現實世界中更長時間的 tirzepatide 使用的潛在持續時間？你認為這可以為付款人的討論提供信息嗎？

And then, Mike, on Mounjaro, a moving target, but how does the prescriber base as of today compare with Trulicity? I'm trying to get a sense for maybe the endocrinology versus primary care mix and utilization in obesity.

然後，邁克，在 Mounjaro，一個移動的目標，但與 Trulicity 相比，今天的處方者基礎如何？我試圖了解內分泌學與初級保健的混合和肥胖症的利用。

Great. Thank you, Geoff. So we'll go to Dan for the question on SURMOUNT-4 and duration of tirzepatide, and then to Mike on the question of how the prescriber base from Mounjaro compares to Trulicity.

偉大的。謝謝你，傑夫。因此，我們將向 Dan 詢問有關 SURMOUNT-4 和 tirzepatide 持續時間的問題，然後向 Mike 詢問 Mounjaro 的處方者基礎與 Trulicity 相比如何的問題。

Yes. Sure. As I was just saying, I mean, obesity is clearly a chronic, often lifetime disease. And for such diseases, patients often need to take therapy for chronically -- potentially the life of the disease here. A lot of times in medicine, that doesn't happen. Of course, people come off of therapies because either the therapy is working, and they think they don't need it anymore or there's a benefit they can't see. I'm not sure either of those are the case for a drug like tirzepatide. People clearly can observe the benefits that the drug is having on their health and perhaps unfortunately, but not different really than any other drug that we have for any other disease. When you stop taking the drug, it's likely that it can no longer work and patients may see that as well.

是的。當然。正如我剛才所說，我的意思是，肥胖顯然是一種慢性疾病，通常是終生疾病。對於此類疾病，患者通常需要長期接受治療——可能是疾病的終生。很多時候在醫學上，這不會發生。當然，人們不再接受治療是因為要么治療有效，要么他們認為自己不再需要它，要么因為看不到治療的好處。我不確定 tirzepatide 這樣的藥物是否屬於這種情況。人們可以清楚地觀察到這種藥物對他們健康的好處，也許不幸的是，但與我們用於治療任何其他疾病的任何其他藥物並沒有什麼不同。當您停止服用該藥物時，它可能不再起作用，患者也可能會看到這一點。

So I think those factors will combine to have a pretty long duration of therapy. We have to wait and see in the marketplace. Maybe Mike has some early signals from patients, but still pretty early on.

所以我認為這些因素結合起來會導致治療時間相當長。我們必須在市場上拭目以待。也許邁克從病人那裡得到了一些早期信號，但還很早。

And Mike?

邁克呢？

Yes. No hard data yet, Dan, on that. But qualitatively, what we hear is what -- patients who've used Mounjaro, what they like and what they realize once they start using it is that it really does reduce the appetite and they enjoy the benefits of reducing appetite. It helps them lose their -- lose weight and stop being as consumed as much during the day, about 80. And we do know that when -- what we heard from our investigators in our studies is that when people stop taking Mounjaro, that their appetite goes back to the level it was before. So that's something very noticeable, something that a patient values from taking the therapy. And then when they stop the therapy, they then see this reversed.

是的。還沒有確鑿的數據，丹，這方面的。但從質量上講，我們所聽到的是——使用過 Mounjaro 的患者，他們喜歡什麼，以及一旦他們開始使用它就會意識到它確實能降低食慾，而且他們享受到降低食慾的好處。它可以幫助他們減掉他們的體重，並停止在白天消耗盡可能多的食物，大約 80 歲。我們確實知道，當我們在研究中從我們的研究人員那裡聽到的是，當人們停止服用 Mounjaro 時，他們的食慾恢復到以前的水平。所以這是非常值得注意的事情，是患者在接受治療時所重視的事情。然後當他們停止治療時，他們就會看到這種情況發生了逆轉。

And so we do believe that people are going to stop and see if they can lose weight. If they can, great. But I do think that they're going to see a very powerful signal very quickly to reinforce going back on the product. So I do think that will help reinforce the chronic use of tirzepatide for type 2 diabetes, and eventually for obesity if we get approved.

所以我們確實相信人們會停下來看看他們是否能減肥。如果他們可以，那就太好了。但我確實認為他們會很快看到一個非常強大的信號，以加強對產品的回歸。所以我確實認為這將有助於加強長期使用 tirzepatide 治療 2 型糖尿病，如果我們獲得批准，最終將用於肥胖症。

The question on Trulicity. Mounjaro -- if you look at Mounjaro's use right now and compare it to how many customers are using that versus Trulicity at this time, it's a lot broader population than we saw with Trulicity just because the market is a lot bigger, a lot more people are writing the treatment.

關於 Trulicity 的問題。 Mounjaro——如果你看看 Mounjaro 現在的使用情況，並將其與目前使用它的客戶數量與使用 Trulicity 的客戶數量進行比較，就會發現它的使用人數比我們使用 Trulicity 時看到的要多得多，因為市場要大得多，人數要多得多正在寫治療。

If you compare Mounjaro to the number of Trulicity writers today, there are more people writing Trulicity just because it's been on the market longer. They've gone through the adoption curve and Trulicity has better access, access and especially in Medicaid that drives additional prescribers to use that.

如果將 Mounjaro 與當今 Trulicity 的作者數量進行比較，就會發現更多的人編寫 Trulicity 只是因為它在市場上的時間更長。他們經歷了採用曲線，Trulicity 有更好的訪問權限，訪問權限，尤其是在推動更多處方者使用它的醫療補助計劃中。

So overall, I'd say that Mounjaro is within the universe of the doctors who write Trulicity at this point.

所以總的來說，我會說 Mounjaro 在此時編寫 Trulicity 的醫生的宇宙中。

The next question is from Tim Anderson from Wolfe Research.

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

I have a question on donanemab. I'm wondering if Lilly would agree that there is highly likely going to be higher ARIA-E and ARIA-H rates with your drug versus lecanemab when TRAILBLAZER-ALZ 2 reports out. The prior data would certainly suggest that.

我有一個關於 donanemab 的問題。我想知道當 TRAILBLAZER-ALZ 2 報告出來時，禮來（Lilly）是否會同意你的藥物與 lecanemab 相比，ARIA-E 和 ARIA-H 率很可能更高。先前的數據肯定會表明這一點。

If so, relative to lecanemab, doesn't that create a potential risk/benefit conundrum for FDA, assuming efficacy comes in around the same levels. I guess the bottom line here, is there a regulatory concern to contemplate maybe this is why the FDA issued the CRL? They want to see the full results from your second study. You don't just want to capture a few more patients to bring that total to 100. Or am I being too bearish here?

如果是這樣，相對於 lecanemab，假設療效大致相同，這不會給 FDA 帶來潛在的風險/收益難題。我想這裡的底線是，是否存在監管問題需要考慮，也許這就是 FDA 發布 CRL 的原因？他們想看到您第二次研究的完整結果。您不只是想再抓幾個病人來使總數達到 100。還是我在這裡太悲觀了？

Thanks, Tim, for the question. We'll go to Dan for this.

謝謝蒂姆提出這個問題。我們會為此去丹。

Yes. Maybe I'll answer the second part of the question first, which is around why did the FDA issue the CRL. I think that the FDA regulations actually suggest that FDA should list all deficiencies in the CRL. We were pretty explicit copying some of the FDA's own words here to investors about what was in the CRL. It didn't discuss issues like ARIA, it was focused on the 12-month exposure. So nothing further to speculate there. I think your question on rates of ARIA-E and ARIA-H comparing across drugs is a complicated one. We did this head-to-head study against aducanumab. I think it's important to use studies like that to compare rates of ARIA, because we've learned that rates of ARIA are highly dependent on the type of patients who enroll, the stage of disease and underlying pathology, baseline characteristics of their brain scans, which are different across lecanemab trials and donanemab trials as well as exactly how you do the MRIs and read them.

是的。也許我會先回答問題的第二部分，即 FDA 為何發布 CRL。我認為 FDA 法規實際上建議 FDA 應該在 CRL 中列出所有缺陷。關於 CRL 中的內容，我們非常明確地向投資者復制了 FDA 自己的話。它沒有討論 ARIA 之類的問題，而是專注於 12 個月的曝光。所以沒有什麼可以進一步推測的了。我認為您關於跨藥物比較 ARIA-E 和 ARIA-H 比率的問題是一個複雜的問題。我們針對 aducanumab 進行了這項頭對頭研究。我認為使用這樣的研究來比較 ARIA 的發生率很重要，因為我們了解到 ARIA 的發生率在很大程度上取決於入組患者的類型、疾病的階段和潛在的病理學、他們腦部掃描的基線特徵，這在 lecanemab 試驗和 donanemab 試驗中是不同的，以及你如何做 MRI 和閱讀它們。

So I'm personally not going to get worked up about rates of asymptomatic radiographic-only ARIA in any drug. I don't think anyone really understands what that means. What we should be focused on, though, is rates of symptomatic ARIA so patients who have ARIA that turns into something they experience, not just a radiographic binding, and particularly rates of serious adverse events resulting from ARIA. We know that in some patients, ARIA can be dangerous, even fatal as we've seen from lecanemab experiences.

因此，我個人不會對任何藥物中無症狀的僅射線照相 ARIA 的發生率感到不滿。我認為沒有人真正理解這意味著什麼。不過，我們應該關注的是症狀性 ARIA 的發生率，因此患有 ARIA 的患者會變成他們所經歷的某種東西，而不僅僅是放射線束縛，尤其是 ARIA 導致的嚴重不良事件的發生率。我們知道，在某些患者中，ARIA 可能是危險的，甚至是致命的，正如我們從 lecanemab 的經驗中看到的那樣。

So that's what we'll be looking out for. I think we still have all the caveats about cross-trial comparisons here, but it's a bit easier to compare those symptomatic or serious events.

這就是我們要尋找的。我認為我們在這裡仍然有關於交叉試驗比較的所有警告，但比較那些有症狀或嚴重的事件要容易一些。

I think in TRAILBLAZER-1, our numbers were very similar to other members of the class. In TRAILBLAZER-4, the numbers look very, very good for that. And we'll wait and see what we have in TRAILBLAZER-2, but my level of concern over that is not high.

我認為在 TRAILBLAZER-1 中，我們的人數與班上其他成員非常相似。在 TRAILBLAZER-4 中，數字看起來非常非常好。我們將拭目以待，看看我們在 TRAILBLAZER-2 中有什麼，但我對此的關注程度並不高。

The next question is from the line of Terence Flynn from Morgan Stanley.

下一個問題來自摩根士丹利的特倫斯弗林。

Maybe a two-part one from me. I guess, first, on Mounjaro manufacturing. I was just wondering if you can tell us if the FDA has completed the inspection of your new North Carolina facility yet.

也許是我的兩部分。我想，首先是關於 Mounjaro 製造。我只是想知道你能否告訴我們 FDA 是否已經完成了對你在北卡羅來納州的新設施的檢查。

And then the other question relates to tirzepatide for obesity. I was wondering if you've had any initial payer conversations yet, and if you're planning to use a priority review voucher for that filing.

然後另一個問題涉及肥胖的 tirzepatide。我想知道您是否已經與付款人進行過任何初步對話，以及您是否打算為該申請使用優先審查憑證。

Thanks, Terence. I think I'll hand over to Anat for commentary on your manufacturing question, and then to Mike on the question about whether there's been any payer conversations on obesity.

謝謝，特倫斯。我想我會轉交給 Anat 對你的製造問題發表評論，然後轉交給 Mike 關於是否有任何關於肥胖的付款人對話的問題。

Terence, to your question on the RTP side, North Carolina, it's progressing on schedule as we had planned. We can't comment on specifics on the FDA interactions, but we're expecting that site to start producing this year, and it's progressing towards that goal.

特倫斯，對於你在北卡羅來納州 RTP 方面的問題，它正在按照我們的計劃按計劃進行。我們無法對 FDA 相互作用的細節發表評論，但我們預計該網站將在今年開始製作，並且正在朝著這個目標前進。

I will mention, important to think about, when we talk about RTP, I think because of the proximal nature of when this site is going to come online, obviously, this is the next large node that's going to come online in terms of capacity for incretin portfolio. But we are making substantial investments beyond RTP. So we've announced a second site in North Carolina, very large site in Concord. And we've announced the expansion of the RTP side, additional sites in Indianapolis -- or north of Indianapolis and a site in Ireland. And as we look at our capital investments in manufacturing sites this year alone, it's probably the largest we've ever had, doubling what we had in 2022. We're looking at about $3.3 billion of investment just this year.

我會提到，重要的是要考慮，當我們談論 RTP 時，我認為由於這個站點何時上線的臨近性質，顯然，這是下一個將在容量方面上線的大節點腸促胰島素組合。但我們正在 RTP 之外進行大量投資。所以我們已經宣佈在北卡羅來納州建立第二個站點，在康科德建立一個非常大的站點。我們還宣布了 RTP 方面的擴展，在印第安納波利斯或印第安納波利斯北部的其他站點以及愛爾蘭的一個站點。僅今年一年，我們就在製造基地進行了資本投資，這可能是我們有史以來最大的投資，是 2022 年的兩倍。僅今年我們就預計投資約 33 億美元。

So we're looking at substantial expansion of capacity really across the globe to support not just Mounjaro, obviously, but the rest of the portfolio. And we have visibility into what's coming as well as the fact that as we've talked about before, we have several products that are part of the same manufacturing network and the same auto-injector platform. So that helps us kind of build that capacity across the Lilly portfolio.

因此，我們正在考慮真正在全球範圍內大幅擴展容量，以支持顯然不僅支持 Mounjaro，還支持其他產品組合。我們對即將發生的事情以及我們之前談到的事實有可見性，我們有幾種產品是同一製造網絡和同一自動注射器平台的一部分。因此，這有助於我們在 Lilly 產品組合中建立這種能力。

Thanks, Anat. Mike, on the second question?

謝謝，阿納特。邁克，關於第二個問題？

Yes. I think a good thing to focus on is access and obesity. I mean you look at the massive size of the obesity market, 110 million people in the U.S., 650 million people globally. But you really see that historically, that the obesity market has really been slow to develop. And it's really because the treatments haven't been adequate.

是的。我認為值得關注的一件好事是訪問和肥胖。我的意思是你看看肥胖市場的巨大規模，美國有 1.1 億人，全球有 6.5 億人。但從歷史上看，肥胖市場確實發展緩慢。這真的是因為治療還不夠。

So the kind of -- the question we had going into this market was if a safe and efficacious treatment was developed, would consumers and health care professionals and payers be interested in using it?

所以我們進入這個市場的問題是，如果開發出一種安全有效的治療方法，消費者、醫療保健專業人員和付款人是否會對使用它感興趣？

Well, based on what we've seen in the marketplace over the past year and on a market research, it's clear that consumers and health care professionals will adopt an efficacious, safe anti-obesity medication if patients can have access to it.

好吧，根據我們過去一年在市場上看到的情況和市場研究，很明顯，如果患者可以獲得有效、安全的抗肥胖藥物，消費者和醫療保健專業人員將採用這種藥物。

So it does come down to payer access, and we're highly focused on doing that. Novo recently stated in their call that 40 million Americans have access to obesity, and the way they talked about it, what's payer access and employers opting into that.

所以它確實歸結為付款人訪問，我們非常專注於這樣做。 Novo 最近在他們的電話中表示，有 4000 萬美國人可能會肥胖，他們談論這個問題的方式、付款人訪問和雇主選擇的方式是什麼。

So if that's where we're at today, that would be a great starting point for access. We're deep into conversations with payers to understand the market and all that. Access discussions haven't started yet, but will shortly. But our focus long term is to improve access for the obesity medications. We are investing significantly to demonstrate the potential health outcome benefits, where people using tirzepatide who live with obesity.

因此，如果這就是我們今天所處的位置，那將是訪問的一個很好的起點。我們正在與付款人進行深入對話，以了解市場等。訪問討論尚未開始，但很快就會開始。但我們的長期重點是改善肥胖藥物的可及性。我們正在大量投資以展示潛在的健康結果益處，其中使用 tirzepatide 的人患有肥胖症。

We're also investing in Phase III programs for people who live with obesity and sleep apnea or heart failure, and these should unlock large segments access for people who live with obesity in commercial, and we hope, Part D.

我們還在為患有肥胖症和睡眠呼吸暫停症或心力衰竭的人投資 III 期計劃，這些應該為肥胖症患者在商業中解鎖大量的訪問權限，我們希望，D 部分。

In addition, in my career, I've seen the power of consumer interest in helping to improve access for medication. And what we've seen over the last year is that people who live with obesity are highly engaged and willing to do much to access effective treatments. They will have an important role and voice with employers and the congressional representatives who advocate for access. So while I think it will take time to establish our ultimate access goal, I'm more encouraged than ever by our potential to unlock the obesity market and help a lot of people. So I'm encouraged, but obviously, a lot of work still to be done.

此外，在我的職業生涯中，我看到了消費者興趣在幫助改善藥物獲取方面的力量。我們在過去一年中看到的是，肥胖症患者積極參與並願意為獲得有效治療付出很多努力。他們將在雇主和倡導准入的國會代表中發揮重要作用和發言權。因此，雖然我認為確定我們最終的可及性目標需要時間，但我比以往任何時候都更加鼓舞我們打開肥胖市場並幫助很多人的潛力。所以我很受鼓舞，但顯然，還有很多工作要做。

The next question is from Steve Scala from Cowen.

下一個問題來自 Cowen 的 Steve Scala。

A question for Anat. I'm not going to get the legislative particulars correct. But just to be clear, doesn't Lilly typically guide on tax rate, assuming an adverse U.S. situation and doesn't typically adjust that until late in the year? And this year, it is assuming no adverse situation, but much earlier in the year?

阿納特的問題。我不會讓立法細節正確。但要明確一點，禮來公司通常不會在假設美國形勢不利的情況下指導稅率，並且通常不會在今年年底之前調整稅率嗎？而今年，它假設沒有不利情況，但在今年早些時候？

If so, can you clarify why you were doing something different this year since it is a profound impact on earnings? And if I could just add on LPA. Dave, Lilly is way behind. How can you catch up?

如果是這樣，你能否澄清為什麼你今年做了一些不同的事情，因為它對收入產生了深遠的影響？如果我可以添加 LPA。戴夫，莉莉遠遠落後。你怎麼能趕上？

Thanks, Steve. I'll go to Anat for the question on the tax rate assumptions, and then I'll go to Dan for your Lp(a) question.

謝謝，史蒂夫。我會去 Anat 詢問有關稅率假設的問題，然後我會去 Dan 詢問您的 Lp(a) 問題。

Thanks, Steve. So here is how we look at this, and I wouldn't read too much into it. Last year, we had assumed based on very broad support for change in this 2017 tax provision that this will, in fact, be enacted by Congress. We assumed late in the year, but it hasn't happened.

謝謝，史蒂夫。所以這就是我們如何看待這個，我不會讀太多。去年，我們假設基於對 2017 年稅收條款變化的廣泛支持，這實際上將由國會頒布。我們假設在今年晚些時候，但它並沒有發生。

So at this point, the only thing we're doing is reflecting reality of the situation we're in. If it does get repealed or deferred, obviously, we'll update accordingly. I don't think the likelihood of that is zero. So it still could happen this year, but it does take Congress -- Congress will need to act to get this going. So we're simply reflecting the current situation.

所以在這一點上，我們唯一要做的就是反映我們所處情況的現實。如果它確實被廢除或推遲，顯然，我們會相應地更新。我不認為這種可能性為零。所以它今年仍有可能發生，但它確實需要國會——國會需要採取行動來實現這一目標。所以我們只是在反映當前的情況。

Okay. I'll start with the Lp(a) question. We have 2 Lp(a) programs. Maybe the easiest one to comment on first is the oral program. And this is a first-in-class, I think probably the only one in clinic here. An oral medication against this target is really a huge feat of molecular engineering. I'm super excited to see the data from this molecule develop and, obviously, the market opportunity for an oral drug for such a widespread condition is very important.

好的。我將從 Lp(a) 問題開始。我們有 2 個 Lp(a) 計劃。也許最容易首先評論的是口語節目。這是一流的，我認為可能是這裡診所中唯一的。針對這一目標的口服藥物確實是分子工程的一項巨大壯舉。我非常高興看到這個分子的數據不斷發展，顯然，針對如此廣泛的疾病的口服藥物的市場機會非常重要。

In terms of the siRNA, you're right to note that a competitor is ahead of us and really just starting the CVOT study. It's a long road to get these drugs to market with outcome studies are needed here to show the benefit. I probably don't get into our differentiation strategy. But of course, we have some ideas here, and we'll move as quickly as possible. I don't see this as a winner-take-all space.

就 siRNA 而言，您正確地註意到競爭對手領先於我們並且實際上才剛剛開始 CVOT 研究。將這些藥物推向市場還有很長的路要走，這裡需要進行結果研究來顯示其益處。我可能不了解我們的差異化戰略。但當然，我們在這裡有一些想法，我們會盡快採取行動。我不認為這是一個贏家通吃的空間。

Maybe just to add, Steve, add on the Lp(a) comment. I think we feel good about where we are with that. But just on the tax thing, there is a difference here where you described it as adverse or beneficial, right? So the -- from a GAAP and non-GAAP accounting, of course, it's a benefit on EPS growth. But actually, from a cash perspective, it goes the other way. So we just wanted to be clear upfront because it's not a one-way benefit we're taking early in the year. There's an adverse cash impact throughout the year and a positive effect on the P&L. It's a little bit different from maybe past assumptions we've made.

也許只是補充一下，史蒂夫，添加 Lp(a) 評論。我認為我們對我們所處的位置感到滿意。但就稅收而言，這裡有一個區別，你把它描述為不利或有利，對吧？所以——從 GAAP 和非 GAAP 會計來看，當然，這對 EPS 增長有好處。但實際上，從現金的角度來看，情況恰恰相反。所以我們只是想提前說清楚，因為這不是我們在今年年初獲得的單向收益。全年都會產生不利的現金影響，並對損益產生積極影響。這可能與我們過去所做的假設有點不同。

The next question is from Louise Chen from Cantor.

下一個問題來自 Cantor 的 Louise Chen。

So I wanted to ask you, what do you think is the minimum amount of relative risk reduction you'd have to see in an outcome study for obesity for payers to be convinced that there's something here?

所以我想問你，你認為在肥胖的結果研究中你必須看到的相對風險降低的最低量是多少才能讓付款人相信這裡有什麼東西？

Thanks, Louise. Mike, do you want to chime in on that around the minimum amount of relative risk reduction we'd expect in an outcome study for obesity?

謝謝，路易絲。邁克，你想談談我們在肥胖癥結果研究中預期的相對風險降低的最低限度嗎？

Yes. That's a good question. I mean first of all, I don't think it's a binary point where all payers are looking for that outcome in order to provide access. I think you're going to see a lot of payers, you already see a lot of payers who provide access for that. And we have an extensive Phase III program not only in CV outcomes, but also the sleep apnea and heart failure to begin to really talk about heart outcomes for many patients who live with obesity.

是的。這是個好問題。我的意思是，首先，我不認為這是所有付款人都在尋找結果以提供訪問權限的二進制點。我認為你會看到很多付款人，你已經看到很多付款人為此提供訪問權限。我們有一個廣泛的 III 期項目，不僅在 CV 結果方面，而且在睡眠呼吸暫停和心力衰竭方面，開始真正談論許多肥胖患者的心臟結果。

With the CV outcomes that we have today, I mean, we're quite confident in our program. And based on what we see with surrogate risk reduction in blood pressure and in lipids, we're fairly confident in our CV profile as well as what we saw with the SURPASS data and our meta-analysis in the SURPASS program.

有了我們今天的 CV 結果，我的意思是，我們對我們的計劃非常有信心。根據我們在血壓和血脂方面的替代風險降低所看到的情況，我們對我們的 CV 概況以及我們在 SURPASS 計劃中看到的 SURPASS 數據和元分析相當有信心。

So I won't give you the exact number, but I think we're pleased with where we're at. And I think we'll be able to demonstrate outcomes that payers will be excited about.

所以我不會給你確切的數字，但我認為我們對我們所處的位置感到滿意。而且我認為我們將能夠展示付款人會感到興奮的結果。

And that comes from David Risinger from SVB Securities.

這來自 SVB Securities 的 David Risinger。

Okay. Looks like we don't have Dave or he's on mute.

好的。看來我們沒有 Dave，或者他處於靜音狀態。

The next question is from Chris Shibutani from Goldman Sachs.

下一個問題來自高盛的 Chris Shibutani。

If I can ask a question on Mounjaro and the interplay with Trulicity. You've commented in the past that in terms of patients on Mounjaro, it has been about less than 10%. That seems to be a little bit higher now. Can you share any thoughts and observations about how you see this progressing on the forward through this year?

如果我可以問一個關於 Mounjaro 和與 Trulicity 的相互作用的問題。您過去曾評論說，就 Mounjaro 的患者而言，大約不到 10%。現在好像有點高了。您能否分享有關您如何看待今年這一進展的任何想法和觀察？

Thanks, Chris, for the question. Mike, we'll go to you for that question on the, I guess, cannibalization from Trulicity figure and how that will progress.

謝謝，克里斯，提出這個問題。邁克，我們會問你這個問題，我想，從 Trulicity 數字中蠶食以及這將如何進展。

Okay. Yes. I mean on that, nothing has changed over what we had talked about earlier, that less than 10% of our scripts we get for Mounjaro come from Trulicity. That hasn't changed over time. It's still a little bit less than 10%.

好的。是的。我的意思是，我們之前談到的內容沒有任何改變，我們為 Mounjaro 獲得的腳本中只有不到 10% 來自 Trulicity。這並沒有隨著時間的推移而改變。它仍然略低於 10%。

And that comes from Umer Raffat from Evercore.

這來自 Evercore 的 Umer Rafat。

There's been a heightened investor focus I feel along the Phase III primary endpoint for donanemab now. And I wonder if there's been any incremental interactions and/or agreement with FDA on the primary endpoint for Phase III. It's a question that I get a lot from investors.

我覺得現在投資者對 donanemab 的 III 期主要終點的關注度有所提高。我想知道是否與 FDA 就 III 期的主要終點進行了任何增量互動和/或達成協議。這是一個我從投資者那裡得到很多的問題。

And also, how are you thinking about this upcoming Phase III? If there were to be a scenario where the MMRM on CDR doesn't agree with iADRS on a patient analysis?

而且，您如何看待即將到來的第三階段？如果存在 CDR 上的 MMRM 與患者分析上的 iADRS 不一致的情況？

Thanks, Umer. We'll go to Dan for the question on endpoints.

謝謝，烏默爾。我們將向 Dan 詢問有關端點的問題。

Yes. Thanks. Clearly, I think there's a lot we can learn from competitor readouts here. And so looking at lecanemab data, in our eyes, I think it actually further validates an endpoint like iADRS. If you just look at the forest plot, for example, there's a lot more homogeneity in effect on an endpoint like iADRS versus CDR Sum of Boxes. So we feel more confident, I would say, than ever before that an endpoint like that is the right way to go.

是的。謝謝。顯然，我認為我們可以從這裡的競爭對手讀數中學到很多東西。所以看看 lecanemab 數據，在我們看來，我認為它實際上進一步驗證了像 iADRS 這樣的端點。例如，如果您只看森林圖，就會發現 iADRS 與 CDR 框總和等端點的同質性要高得多。因此，我想說，我們比以往任何時候都更有信心，這樣的終點是正確的方法。

On the other hand, I think the -- you could take the position that since lecanemab hit CDR Sum of Boxes, people might say, "Well, then it's achievable, and you guys should do it, too." So there's some pushes and some takes there. But on the whole, still feeling good about iADRS as a primary outcome.

另一方面，我認為——你可以採取這樣的立場，因為 lecanemab 達到了 CDR 盒的總和，人們可能會說，“好吧，那是可以實現的，你們也應該這樣做。”所以有一些推動和一些接受。但總的來說，仍然對 iADRS 作為主要結果感覺良好。

When you ask, though, what happens if you hit one outcome and not the other? That's surely a difficult situation to be in. We want to understand why that happened. If that were to happen, where the irregularities in CDR Sum of Boxes that could explain it, what did the rest of the secondaries look like? Always best to hit all of your outcomes in a clinical trial. Failing that, you want to hit your primary in as many secondaries as possible. So let's wait and see.

但是，當你問，如果你達到一個結果而不是另一個結果會怎樣？這肯定是一個困難的局面。我們想了解為什麼會這樣。如果發生這種情況，那麼 CDR 框總和中的不規則性可以解釋它，其餘的次級看起來像什麼？始終最好在臨床試驗中達到所有結果。如果做不到這一點，您希望在盡可能多的次級中擊中您的初級。所以讓我們拭目以待。

That question is from Mohit Bansal from Wells Fargo.

這個問題來自富國銀行的 Mohit Bansal。

Maybe a question regarding your next-generation Alzheimer's drug. I cannot pronounce the name, but remternetug. I mean I'll learn it. But how does it differ, is similar versus donanemab? Asking -- because I mean, you're running a Phase III trial with subcu here. So what would be the read-through for this particular asset based on the outcome of donanemab Phase III trial?

也許是關於您的下一代阿爾茨海默氏症藥物的問題。我不能發音的名字，但 remternetug。我的意思是我會學習它。但它有何不同，與 donanemab 相似嗎？問——因為我的意思是，你在這裡用 subcu 進行 III 期試驗。那麼，根據 donanemab III 期試驗的結果，該特定資產的通讀量是多少？

Dan, do you want to talk a little bit about remternetug?

Dan，你想談談 remternetug 嗎？

Yes. I think you've got it basically right. Remternetug is a new medicine, a new molecule, but it's an antibody against the same type of epitope that donanemab has, which is this N3pG form of A beta. So a very equivalent mechanism of action. Maybe a little better potency and certainly better drug properties, including no ADAs and formulation things. So the rationale here is to give improved dosing options to patients.

是的。我認為你基本上是對的。 Remternetug 是一種新藥，一種新分子，但它是針對多納單抗所具有的相同類型表位的抗體，即 A β 的 N3pG 形式。所以一個非常等效的作用機制。也許效力更好一點，當然也有更好的藥物特性，包括沒有 ADAs 和配方的東西。因此，這裡的基本原理是為患者提供改進的劑量選擇。

Could we get even faster plaque clearance, could it be with fewer doses, could it be subcutaneous? Those are the types of things that we're currently exploring. The Phase III is designed with a bit of a run-in. We're in that portion right now to finalize our dosing strategy and then expand it.

我們能否更快地清除斑塊，是否可以使用更少的劑量，是否可以皮下注射？這些是我們目前正在探索的事物類型。第三階段的設計有點磨合。我們現在正在那部分完成我們的劑量策略，然後擴展它。

Obviously, if donanemab is disappointing, there would be read-through through remternetug. On the other hand, if donanemab exceeds expectations, I would expect that to read through as well.

顯然，如果 donanemab 令人失望，將通過 remternetug 通讀。另一方面，如果 donanemab 超出預期，我希望它也能通讀。

The next question is Evan Seigerman from BMO.

下一個問題是來自 BMO 的 Evan Seigerman。

While much of the discussion on Medicare coverage is in Alzheimer's, we know that Medicare really doesn't pay for obesity drugs. Can you just talk about your efforts to help Medicare patients get coverage for obesity drugs, including potentially Mounjaro, if unapproved. Maybe add some parameters around what that additional population could look like from a revenue opportunity perspective.

雖然關於醫療保險覆蓋範圍的大部分討論都是關於阿爾茨海默氏症，但我們知道醫療保險確實不支付肥胖藥物的費用。如果未經批准，您能否談談您為幫助 Medicare 患者獲得肥胖藥物（包括潛在的 Mounjaro）承保所做的努力。從收入機會的角度來看，也許可以圍繞增加的人口可能是什麼樣子添加一些參數。

Thanks, Evan, for the question. I'll hand over to Mike. Mike, do you want to talk about the potential for Medicare to cover obesity?

謝謝埃文提出這個問題。我會交給邁克。邁克，你想談談醫療保險覆蓋肥胖症的潛力嗎？

Okay. Sure. Yes, good question. I mean it's going to take legislative action in order to allow the obesity medications to be covered on Medicare Part D. So there is the Treat and Reduce Obesity Act. The acronym for that is TROA. And there's a large growing bipartisan support for TROA, a little over 100 congressmen and senators, Congress people and senators are behind the program. And it's growing more and more support across Washington. We're eager to see an advanced (inaudible) Process. It would be great for the company, country. America needs to take action and drastically reduce the number of people living with obesity, and this [sort of solution] would be an important step for this goal. We'll also support the [solution] and continue to work to advocate for it.

好的。當然。是的，好問題。我的意思是它將採取立法行動，以允許肥胖藥物在 Medicare D 部分中得到涵蓋。所以有治療和減少肥胖症法案。首字母縮寫詞是 TROA。兩黨對 TROA 的支持越來越多，超過 100 名國會議員和參議員支持該計劃。它在華盛頓得到越來越多的支持。我們渴望看到先進的（聽不清）流程。這對公司、國家來說都很棒。美國需要採取行動，大幅減少肥胖症患者的數量，而這種[某種解決方案]將是實現這一目標的重要一步。我們也將支持 [解決方案] 並繼續努力倡導它。

The next question is from Trung Huynh from Credit Suisse.

下一個問題來自瑞士信貸的 Trung Huynh。

Trung Huynh from Credit Suisse. Last month, the American Academy of Pediatrics released their guidelines to treat childhood obesity. In those guidelines, they recommended a lifestyle intervention, obviously, is the core component. But also, they said they would consider treatment with anti-obesity medications. So I thought what's your thoughts on anti-obesity medications in children? Is this a scenario that you are moving into or considering moving into? Do you have any trials with children or adolescents?

瑞士信貸的 Trung Huynh。上個月，美國兒科學會發布了治療兒童肥胖症的指南。在這些指南中，他們推薦的生活方式乾預顯然是核心組成部分。而且，他們表示他們會考慮使用抗肥胖藥物進行治療。所以我想你對兒童抗肥胖藥物有什麼看法？這是您正在進入或考慮進入的場景嗎？您對兒童或青少年進行過任何試驗嗎？

Thanks, Trung, for the question. Mike, over to you again, comment on these recent guidelines that were put out.

謝謝 Trung 的提問。邁克，再次請您對最近發布的這些指南發表評論。

Yes. Thanks. I mean this is a significant unmet need. Back to the question that we asked earlier about the Treat and Reduce Obesity Act. We need to improve the health of America. We have too many people who live with obesity in the U.S., and that includes, unfortunately, adolescents and kids. So I think they took the right action in order to really identify this as an issue that health care professionals do need to pay close attention to. We obviously always advocate for diet and exercise is the first approach of this. But if that's not successful, then your really only option at that point is medication treatment. We do think it's important and responsible for us to test tirzepatide in kids and adolescents, and we have activity ongoing to do that.

是的。謝謝。我的意思是這是一個重要的未滿足需求。回到我們之前提出的關於《治療和減少肥胖法案》的問題。我們需要改善美國的健康狀況。在美國，我們有太多肥胖的人，不幸的是，其中包括青少年和兒童。所以我認為他們採取了正確的行動，以便真正將此確定為醫療保健專業人員確實需要密切關注的問題。我們顯然一直提倡飲食和運動是第一個方法。但如果那不成功，那麼此時你真正唯一的選擇就是藥物治療。我們確實認為在兒童和青少年中測試 tirzepatide 對我們來說很重要，也很負責任，我們正在進行這方面的活動。

The next question is from Carter Gould from Barclays.

下一個問題來自巴克萊銀行的卡特古爾德。

Great. I guess one for Anat. Back in December, you highlighted austerity measures in Europe as a potential risk. At that time, that was a bit of a unique position. We hadn't heard that from many companies. Since that time, we've heard kind of similar messaging from some but not all. And apologies if I missed it, I don't think I heard anything today on this front. So I know it's only been sort of 45 days or so since you made those comments, but any advances in sort of how you're thinking about this? And any specific products or countries we should think about that impact?

偉大的。我猜是給 Anat 的。早在去年 12 月，您就強調歐洲的緊縮措施是一個潛在風險。那時候，那是有點得天獨厚的地位。我們沒有從很多公司那裡聽說過。從那時起，我們聽到了一些但不是全部的類似消息。如果我錯過了，我深表歉意，我想我今天在這方面沒有聽到任何消息。所以我知道距離你發表這些評論只有 45 天左右的時間，但是你對這個問題的看法有什麼進展嗎？我們應該考慮這種影響的任何特定產品或國家？

Thanks, Carter, for the question. I'm actually going to hand this over to Ilya Yuffa, who's our President of Lilly International, to comment on the European austerity measures.

卡特，謝謝你提出這個問題。實際上，我將把這個交給我們的禮來國際總裁 Ilya Yuffa 來評論歐洲的緊縮措施。

Yes, I appreciate the question. There have been a number of markets in Europe that have taken some austerity measures, partially due to Ukraine crisis and energy crisis and inflation in Europe. We have seen Germany, France, obviously, the U.K. voluntary system, we think, is broken, and so we exited that. And so we -- there are some austerity measures in there. We've contemplated that into our guidance for '23. And the overall impact is modest relative to historical declines in price in prior years. We expect that to continue to be in that mid-single-digit decline in price in Europe.

是的，我很欣賞這個問題。歐洲已經有一些市場採取了一些緊縮措施，部分原因是烏克蘭危機和能源危機以及歐洲的通貨膨脹。我們已經看到德國、法國，顯然，我們認為英國的自願制度已經崩潰，所以我們退出了。所以我們 - 那裡有一些緊縮措施。我們已經將其考慮到我們對 23 年的指導中。相對於前幾年價格的歷史下降，總體影響是溫和的。我們預計歐洲的價格將繼續保持中個位數的跌幅。

The next question is from Andrew Baum from Citi.

下一個問題來自花旗銀行的 Andrew Baum。

A question on U.S. commercial access for GLP-1 agonist. First, could you share with us how you're thinking about modeling, the impact of the IRA in terms of GLP-1 uptake increasing as a result of the co-pay cap? And is that additionally benefiting from the reduction in free drug program. How significant is it given the patients still got to find $2,000 per annum?

關於美國 GLP-1 激動劑商業准入的問題。首先，您能否與我們分享您是如何考慮建模的，IRA 在 GLP-1 吸收方面的影響因共同支付上限而增加？並且還受益於免費藥物計劃的減少。鑑於患者每年仍需找到 2,000 美元，這有多重要？

And then second, in relation to the oral DPP-4 market, which is still a very, very substantial $14 billion market. You have a category of drugs extensively, which may offer considerable advantages in efficacy for glycemia and weight. But I'm reminded of the stickiness of the [scenario you're with] in the prior period. To what extent do you think managed market is going to preclude your ability to penetrate that segment with all GLP-1s just on the basis of generic DPP-4s?

其次，關於口服 DPP-4 市場，這仍然是一個非常非常大的 140 億美元市場。您擁有廣泛的一類藥物，它們可能在降低血糖和體重方面具有相當大的優勢。但我想起了前期[你所處的場景]的粘性。您認為託管市場將在多大程度上阻止您僅基於通用 DPP-4 以所有 GLP-1 滲透該細分市場的能力？

Thanks, Andrew, for the wide-ranging question on diabetes. I'll hand over to Mike first to talk about your question regarding potential impact of the IRA on access for GLP-1. And then the second question around how oral GLP might fit in given the stickiness of some of the older diabetes medications. Mike?

謝謝，安德魯，關於糖尿病的廣泛問題。我將首先交給 Mike 來談談你關於 IRA 對 GLP-1 訪問的潛在影響的問題。然後是第二個問題，考慮到一些較老的糖尿病藥物的粘性，口服 GLP 可能如何適用。麥克風？

Yes. Good questions. On the IRA side of it, it will benefit patients who live with diabetes who use GLPs and are in Medicare Part D. Out-of-pocket cost will go down. We have, I would say, a small or moderate impact on GLP sales or just probably lower rates of abandonment than what we'd see at higher out-of-pocket costs.

是的。好問題。在 IRA 方面，它將使使用 GLP 並在 Medicare D 部分的糖尿病患者受益。自付費用將下降。我想說，我們對 GLP 銷售的影響很小或中等，或者放棄率可能低於我們在更高的自付費用中看到的。

As it comes to the oral DPP-4, the perceptions of oral DPP-4s have really declined over the last 5 years and really being replaced by SGLT-2s and GLP lose. So I don't see much of an impact of DPP-4s going off path in the U.S. or other markets.

關於口服 DPP-4，口服 DPP-4 的認知度在過去 5 年中確實有所下降，真正被 SGLT-2 取代，GLP 丟失。因此，我認為 DPP-4 在美國或其他市場偏離軌道不會產生太大影響。

And that's from Robyn Karnauskas from Truist Securities.

這是來自 Truist Securities 的 Robyn Karnauskas。

Great. I was just thinking more about some of the launches that are coming up, but I know these maybe a [little were out]. But for mirikizumab, and I always get this wrong, sorry. But for UC, can you just talk a little bit about given how much promotion there's been for SKYRIZI and RINVOQ as you move into also Crohn's with data reading out soon. Like how do you see like competing in that market? Can you start launching? Do you have to be DTC heavy because it seems like they're very prominent? Like what about the launch dynamics?

偉大的。我只是在考慮更多即將推出的一些產品，但我知道這些可能 [有點出局了]。但是對於 mirikizumab，我總是弄錯了，抱歉。但是對於 UC，你能不能談談考慮到 SKYRIZI 和 RINVOQ 有多大的提升，因為你也進入了克羅恩病，很快就會讀出數據。比如你如何看待在那個市場上的競爭？可以開始發射了嗎？是否因為 DTC 看起來非常突出而必須使用大量 DTC？比如發射動態怎麼樣？

And then second, for lebrikizumab, the same question here. Atopic dermatitis is getting pretty crowded. What kind of pushes and pulls might you need to use to get quicker uptake in atopic derm?

其次，對於 lebrikizumab，同樣的問題在這裡。特應性皮炎變得非常擁擠。您可能需要使用什麼樣的推拉方式才能更快地吸收特應性皮膚？

Thanks, Robyn, for the questions. I will go to Patrik Jonsson for both of these, first on mirikizumab and competition in the UC market and then on lebrikizumab. Patrik?

謝謝羅賓提出的問題。我會去 Patrik Jonsson 尋求這兩個方面的幫助，首先是關於 mirikizumab 和 UC 市場的競爭，然後是 lebrikizumab。帕特里克？

Thank you very much. Well, overall, we feel very good with the data we have seen on mirikizumab. If we look at the 52 weeks, we have more than 50% clinical remission, and we see statistical and clinically meaningful improvements across both clinical, symptomatic, endoscopic and histologic endpoints.

非常感謝。嗯，總的來說，我們對我們在米利珠單抗上看到的數據感到非常滿意。如果我們觀察 52 週，我們有超過 50% 的臨床緩解，並且我們看到臨床、症狀、內窺鏡和組織學終點方面的統計和臨床有意義的改善。

What I think is important that if you look at the patient populations with ulcerative colitis, we saw the same results across the bio-naïve and the bio-failure patients. So I think we're extremely well positioned for the launch here. We also demonstrated [on a factor], but it's extremely important for patients, bowel urgency. More than 40% of patients were either completely or almost bowel urgency treated at week 52.

我認為重要的是，如果你觀察患有潰瘍性結腸炎的患者群體，我們會在未接受生物治療的患者和生物治療失敗的患者中看到相同的結果。所以我認為我們非常適合在這裡推出。我們還證明了 [關於一個因素]，但它對患者來說非常重要，即腸緊迫感。超過 40% 的患者在第 52 週時完全或幾乎治療了腸急症。

So therefore, we believe we have a first-in-class asset here that probably initially will be used mainly second line for those that haven't responded appropriately to TNFs and similar. But we believe that long term, we are positioned for a first-line placement in treatment of ulcerative colitis.

因此，我們相信我們在這裡擁有一流的資產，最初可能主要用於那些對 TNF 和類似藥物沒有適當反應的人的二線。但我們相信，從長遠來看，我們處於治療潰瘍性結腸炎的一線位置。

And yes, so the outlook for mirikizumab, it's exciting from a competitive landscape perspective. We don't have to have data. But if we compare the data we have seen so far, we believe that miri compares very favorable both versus what's currently in the marketplace as well as what's in the pipeline with other companies across JAK inhibitors, S1Ps and other IL-23s as well. So exciting to launch miri the first half of this year.

是的，從競爭格局的角度來看，mirikizumab 的前景令人興奮。我們不需要數據。但如果我們比較我們目前看到的數據，我們相信 miri 與目前市場上的產品以及與其他公司在 JAK 抑製劑、S1P 和其他 IL-23 方面的產品相比都非常有利。今年上半年推出 miri 真是令人興奮。

When it comes to lebri, I think actually, we are uniquely positioned to really upgrade the expected outcomes of patients with atopic dermatitis. We have here an asset that is actually targeting the most relevant cytokine when it comes to treating atopic dermatitis, IL-13. And it does that with a high binding affinity, high potency and a slow off-rate. And I think that probably explains the data that we have seen so far. We're extremely pleased with the Phase III data, and we saw more than 80% of patients achieving skin clearance at week 16, maintaining that at week 52. But also very importantly, statistical and clinically meaningful improvements across both each, which is probably the most disturbing factor for patients with atopic dermatitis, sleep and quality of life. And we saw similar results across both the Q2W and Q4W formulation.

談到 lebri，我認為實際上，我們處於獨特的位置，可以真正提升特應性皮炎患者的預期結果。我們這裡有一項資產，在治療特應性皮炎 IL-13 方面，它實際上是針對最相關的細胞因子。它具有高結合親和力、高效力和緩慢的解離率。我認為這可能解釋了我們迄今為止看到的數據。我們對 III 期數據非常滿意，我們看到超過 80% 的患者在第 16 週時實現了皮膚清除，並在第 52 週時保持這一水平。但同樣非常重要的是，兩者均有統計和臨床意義的改善，這可能是特應性皮炎患者最擔心的因素是睡眠和生活質量。我們在 Q2W 和 Q4W 公式中看到了類似的結果。

We actually believe that lebrikizumab has the potential to become a first-line biologic. It's important to have in mind that we announced the submission at the Q3 earnings call, and we expect that traditional regulatory pathway. Yes, we will not launch until most likely Q4 of 2023.

我們實際上相信 lebrikizumab 有潛力成為一線生物製劑。重要的是要記住，我們在第三季度財報電話會議上宣布了提交，我們期待傳統的監管途徑。是的，我們很可能要到 2023 年第四季度才會推出。

But a lot of excitement from both health care providers, the top-tier community as well on the payers to get leverage to the market.

但醫療保健提供者、頂級社區以及付款人都對獲得市場影響力感到非常興奮。

Thank you, Patrik. Dave, to wrap up?

謝謝你，帕特里克。戴夫，要結束了嗎？

Great. I think that's the last question. I appreciate the questions across the portfolio. And we appreciate your participation in today's earnings call and your interest in our company.

偉大的。我認為這是最後一個問題。我很欣賞整個投資組合的問題。我們感謝您參加今天的財報電話會議以及您對我們公司的興趣。

2022 was another productive year for the company, and we generated strong financial results and delivered important pipeline progress in each of our core therapeutic areas on behalf of the patients we serve. We aim to continue our momentum in 2023 and execute on the meaningful launch and pipeline opportunities that we have ahead of us.

2022 年對公司來說又是富有成效的一年，我們取得了強勁的財務業績，並代表我們所服務的患者在我們的每個核心治療領域取得了重要的管道進展。我們的目標是在 2023 年繼續我們的勢頭，並執行我們面前有意義的發布和管道機會。

So thanks for dialing in, and please follow up with IR if you have questions that we didn't get to today. Have a great day.

感謝您的撥入，如果您有我們今天沒有解決的問題，請跟進 IR。祝你有美好的一天。

Thank you. And ladies and gentlemen, this does conclude our conference for today. And this conference will be made available for replay beginning at 1:00 today, running through February 9 at midnight. And you may access the AT&T replay system at any time by dialing (866) 207-1041 and entering the access code 4283950. International dialers can call (402) 970-0847.

謝謝。女士們，先生們，我們今天的會議到此結束。本次會議將從今天凌晨 1:00 開始重播，一直持續到 2 月 9 日午夜。您可以隨時撥打 (866) 207-1041 並輸入接入碼 4283950 來訪問 AT&T 重放系統。國際撥號器可以撥打 (402) 970-0847。

And that does conclude our conference for today. Thank you for your participation and for using AT&T event conferencing. You may now disconnect.

這確實結束了我們今天的會議。感謝您的參與和使用 AT&T 活動會議。您現在可以斷開連接。