禮來公司 (LLY) 2023 Q2 法說會逐字稿

Ladies and gentlemen, thank you for standing by, and welcome to the Lilly Q2 2023 Earnings Call. (Operator Instructions)

女士們、先生們，感謝大家的支持，歡迎參加禮來公司 2023 年第二季度財報電話會議。 （操作員說明）

I would now like to turn the conference over to your host, Joe Fletcher, Senior Vice President of Investor Relations. Please go ahead.

現在我想將會議交給東道主投資者關係高級副總裁喬·弗萊徹 (Joe Fletcher)。請繼續。

Good morning. Thank you for joining us for Eli Lilly and Company's Q2 2023 Earnings Call. I'm Joe Fletcher, Senior Vice President of Investor Relations. And joining me on today's call are Dave Ricks, Lilly's Chair and CEO; Anat Ashkenazi, Chief Financial Officer; Dr. Dan Skovronsky, Chief Scientific and Medical Officer; Anne White, President of Lilly Neuroscience; Ilya Yuffa, President of Lilly International; Jake Van Naarden, President of Loxo at Lilly; Mike Mason, President of Lilly Diabetes; and Patrik Jonsson, President of Lilly Immunology and Lilly U.S.A. We're also joined by Michaela Irons, Mike Springnether and Lauren Zierki of the Investor Relations team.

早上好。感謝您參加禮來公司 2023 年第二季度財報電話會議。我是喬·弗萊徹，投資者關係高級副總裁。與我一起參加今天電話會議的還有禮來公司 (Lilly) 董事長兼首席執行官戴夫·里克斯 (Dave Ricks)；阿納特·阿什肯納齊 (Anat Ashkenazi)，首席財務官； Dan Skovronsky 博士，首席科學和醫療官； Anne White，禮來神經科學公司總裁；伊利亞·尤法 (Ilya Yuffa)，禮來國際公司總裁； Jake Van Naarden，禮來公司 Loxo 總裁；邁克·梅森 (Mike Mason)，禮來糖尿病公司總裁；禮來免疫學公司和禮來美國公司總裁帕特里克·瓊森 (Patrik Jonsson) 也加入了我們的行列，投資者關係團隊的 Michaela Irons、Mike Springnether 和 Lauren Zierki 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.

在本次電話會議中，我們預計將根據當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會存在重大差異。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提交的表格10-K 以及後續提交的表格10-Q 和8-K 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.

我們提供有關我們的產品和管道的信息是為了投資界的利益。它的目的不是為了促銷，也不足以製定決策。

As we transition to our prepared remarks, please note that our commentary will focus on non-GAAP financial measures.

當我們轉向準備好的評論時，請注意，我們的評論將重點關注非公認會計準則財務指標。

Now I'll turn over the call to Dave.

現在我將把電話轉給戴夫。

Thanks, Joe. In the second quarter, Lilly's momentum continued. We advanced our R&D pipeline, progressed our ambitious manufacturing agenda and delivered strong financial results. Our business saw an acceleration of revenue growth driven by Mounjaro, Verzenio and Jardiance. As base period headwinds from COVID-19 antibody revenue and Alimta's loss of exclusivity recede, we do expect strong growth to continue in the quarters ahead.

謝謝，喬。第二季度，禮來繼續保持勢頭。我們推進了研發渠道，推進了雄心勃勃的製造議程，並取得了強勁的財務業績。在 Mounjaro、Verzenio 和 Jardiance 的推動下，我們的業務收入增長加速。隨著 COVID-19 抗體收入和 Alimta 失去獨家經營權帶來的基期不利因素消退，我們預計未來幾個季度將繼續強勁增長。

Lilly has made substantial progress in advancing our pipeline of innovative medicines in recent years, but the past few months have been particularly noteworthy. In early May, we shared the top line results of the Phase III TRAILBLAZER-ALZ 2 trial, which showed donanemab treatment slowed clinical decline in Alzheimer's by 35%. While differences in enrollment criteria and study design make cross-trial comparisons difficult, this represents the greatest percentage cognitive slowing in a primary end point of any disease-modifying Alzheimer's disease treatment reported to date, and the only Phase II to Phase III replication to date.

近年來，禮來公司在推進我們的創新藥物產品線方面取得了實質性進展，但過去幾個月尤其值得注意。 5 月初，我們分享了 III 期 TRAILBLAZER-ALZ 2 試驗的主要結果，該試驗顯示多納單抗治療使阿爾茨海默病的臨床衰退減緩了 35%。雖然入組標準和研究設計的差異使得交叉試驗比較變得困難，但這代表了迄今為止報導的任何緩解阿爾茨海默病治療疾病的主要終點中認知減緩的最大百分比，也是迄今為止唯一的II 期到III 期復制。

3 weeks ago at the Alzheimer's Association International Conference in Amsterdam and simultaneously published in JAMA, we shared the detailed results, including new analysis, which demonstrates the potential of even greater cognitive slowing in patients in the earlier stages of Alzheimer's disease.

三週前，在阿姆斯特丹舉行的阿爾茨海默病協會國際會議上，我們分享了詳細的結果，包括新的分析，該結果表明阿爾茨海默病早期階段患者的認知能力可能會進一步減慢。

At the ADA scientific sessions in June, we shared positive Phase II data on 2 next-generation diabetes and obesity product candidates: orforglipron and retatrutide. And less than 2 weeks ago, we shared top line results from the SURMOUNT-3 and SURMOUNT-4 Phase III trials, which showed participants on tirzepatide following intensive lifestyle intervention or with continued tirzepatide treatment, achieved up to 26.6% mean weight loss. Dan will share more perspectives in his R&D update on these and other exciting areas of pipeline progress.

在 6 月的 ADA 科學會議上，我們分享了 2 種下一代糖尿病和肥胖候選產品：orforglipron 和 retatrutide 的積極的 II 期數據。不到兩週前，我們分享了SURMOUNT-3 和SURMOUNT-4 III 期試驗的主要結果，該試驗顯示，服用替澤帕肽的參與者在強化生活方式乾預或持續替澤帕肽治療後，平均體重減輕了26.6%。丹將在他的研發更新中分享更多關於這些和其他令人興奮的管道進展領域的觀點。

Moving to our results. You can see on Slide 4 the continued progress made on our strategic deliverables so far this year. Excluding revenue from Baqsimi and from the sales of COVID-19 antibodies in 2022, Q2 revenue grew 22% on 23% volume growth. Volume growth in Q2 was driven by Mounjaro, which leads our new products category. That category also includes Jaypirca and now Omvoh, which saw its first sales in Japan in Q2 and launched in Germany in July.

轉向我們的結果。您可以在幻燈片 4 中看到今年迄今為止我們在戰略交付成果方面取得的持續進展。不包括 Baqsimi 的收入和 2022 年 COVID-19 抗體的銷售收入，第二季度收入增長 22%，銷量增長 23%。第二季度銷量增長是由 Mounjaro 推動的，Mounjaro 引領了我們的新產品類別。該類別還包括 Jaypirca 和現在的 Omvoh，後者於第二季度在日本首次銷售，並於 7 月在德國推出。

In the second quarter of this year, new products and growth products categories combined contributed approximately 26 percentage points of volume growth. These products, coupled with potential upcoming launches, solidify Lilly's strong growth profile through this decade.

今年第二季度，新產品和增長產品類別合計貢獻了約26個百分點的銷量增長。這些產品，加上即將推出的潛在產品，鞏固了禮來公司在這十年中的強勁增長勢頭。

We've had several important pipeline updates since our Q1 earnings call. For mirikizumab, approval in the EU and resubmission of our U.S. application with regulatory action expected by the end of this year. Regulatory submissions in the U.S. for tirzepatide for chronic weight management; regulatory submission of donanemab for traditional approval to the FDA and EMA following the positive Phase III results from the TRAILBLAZER-ALZ 2 trial; and positive Phase III top line readouts for SURMOUNT-3 and 4 in the third and fourth global studies evaluating tirzepatide in chronic weight management.

自第一季度財報電話會議以來，我們已經進行了多項重要的管道更新。對於 mirikizumab，我們將在歐盟獲得批准，並在美國重新提交申請，預計將於今年年底採取監管行動。美國針對用於長期體重管理的替西帕肽提交的監管申請；在 TRAILBLAZER-ALZ 2 試驗取得積極的 III 期結果後，向 FDA 和 EMA 提交了 donanemab 的監管申請，以進行傳統批准；在評估替澤帕肽在慢性體重管理中的第三項和第四項全球研究中，SURMOUNT-3 和 4 的 III 期頂線讀數呈陽性。

The second quarter also was productive for business development. We've commented in the past on our active exploration and pursuit of external innovation and are pleased to have announced agreements to acquire 2 clinical-stage companies in the second quarter: DICE Therapeutics and Versanis Bio. These companies operate in different therapeutic areas, and each is a fit with Lilly's strategy.

第二季度的業務發展也富有成效。我們過去曾評論過我們對外部創新的積極探索和追求，並很高興宣佈在第二季度收購兩家臨床階段公司的協議：DICE Therapeutics 和 Versanis Bio。這些公司在不同的治療領域開展業務，每家都符合禮來公司的戰略。

We also closed the sale of global rights to Baqsimi, and the financial impact of this transaction is reflected in our Q2 results. After quarter end, we closed the sale of rights to our olanzapine portfolio, which will be reflected in our Q3 financial results. Both these transactions are now incorporated into our updated 2023 financial guidance.

我們還完成了向 Baqsimi 出售全球版權的交易，此次交易的財務影響反映在我們第二季度的業績中。季度末後，我們完成了奧氮平投資組合權利的出售，這將反映在我們第三季度的財務業績中。這兩筆交易現已納入我們更新的 2023 年財務指南中。

We continued to progress the most ambitious manufacturing expansion agenda in the 147 history of our company. We're happy to share that commercial production to support our incretin portfolio has begun at our Research Triangle Park site in North Carolina. Beyond the capacity expansion that will come as we ramp production at this site, we're also pursuing other near-term paths to expand access to our incretins to patients around the world. Anat will provide more detail on these efforts.

我們繼續推進公司 147 年來最雄心勃勃的製造擴張議程。我們很高興地告訴大家，支持我們的腸促胰素產品組合的商業生產已經在我們位於北卡羅來納州的三角研究園基地開始。除了隨著我們在該工廠提高產量而進行的產能擴張之外，我們還在尋求其他近期途徑，以擴大我們的腸促胰島素對世界各地患者的使用範圍。 Anat 將提供有關這些努力的更多細節。

And finally, we distributed over $1 billion in dividends this quarter. On Slide 5, you'll see a list of key events since our Q1 earnings call, including several important regulatory, clinical and other updates we're sharing today.

最後，本季度我們派發了超過 10 億美元的股息。在幻燈片 5 上，您將看到自第一季度財報電話會議以來的關鍵事件列表，包括我們今天分享的幾項重要的監管、臨床和其他更新。

So without further ado, I'll turn this over to Anat to share our Q2 results.

因此，言歸正傳，我將把這個交給 Anat 來分享我們第二季度的結果。

Thanks, Dave. Slide 6 summarizes financial performance in the second quarter of 2023. I'll focus my comments today on non-GAAP performance. In Q2, revenue increased 28% versus Q2 of 2022. Excluding revenue from Baqsimi and from COVID-19 antibodies in the base period, revenue increased 22% or 23% on a constant currency basis. This acceleration on revenue growth was achieved despite lingering headwinds from Alimta's loss of exclusivity in the United States, which occurred in the first half of last year, and the effects of which should normalize going forward.

謝謝，戴夫。第 6 張幻燈片總結了 2023 年第二季度的財務業績。今天我將重點討論非 GAAP 業績。第二季度的收入比 2022 年第二季度增長了 28%。不包括基期內 Baqsimi 和 COVID-19 抗體的收入，按固定匯率計算，收入增長了 22% 或 23%。儘管去年上半年 Alimta 在美國失去獨家經營權帶來了揮之不去的阻力，但其收入增長的加速還是實現了，其影響在未來應該會正常化。

Gross margin as a percent of revenue was flat in Q2 at 79.8%. Gross margin in the quarter benefited from product mix, including onetime revenue from the sales of rights to Baqsimi, which was offset by increases in manufacturing expenses related to labor costs and our investments in capacity expansion. Total operating expenses increased 14% this quarter. Marketing, selling and administrative expenses increased 18%, driven by higher marketing and selling expenses associated with recent and upcoming new product launches and additional indications. R&D expenses increased 32%, driven by higher development expenses for late-stage assets and additional investments in early-stage research.

第二季度毛利率佔收入的百分比持平，為 79.8%。本季度的毛利率受益於產品組合，包括出售 Baqsimi 權利的一次性收入，但該收入被與勞動力成本相關的製造費用增加和我們在產能擴張方面的投資所抵消。本季度總運營費用增加了 14%。由於近期和即將推出的新產品以及其他適應症相關的營銷和銷售費用增加，營銷、銷售和管理費用增長了 18%。由於後期資產的開發費用增加以及早期研究的額外投資，研發費用增長了 32%。

This quarter, we recognized acquired IPR&D charges of $97 million or $0.09 of EPS. In Q2 2022, acquired IPR&D charges totaled $440 million or $0.46 of EPS. Operating income increased 69% in Q2 driven by higher revenue, including revenue associated with the sales of rights for Baqsimi and lower IPR&D charges, partially offset by higher R&D and SG&A expenses. Operating income as a percent of revenue was 27% for the quarter and reflected a negative impact of approximately 115 basis points attributable to acquired IPR&D charges.

本季度，我們確認收購的 IPR&D 費用為 9700 萬美元，即每股收益 0.09 美元。 2022 年第二季度，收購的知識產權與研發費用總計 4.4 億美元，相當於每股收益 0.46 美元。在收入增加的推動下，第二季度營業收入增長了 69%，其中包括與 Baqsimi 權利銷售相關的收入以及較低的 IPR&D 費用，但部分被較高的研發和 SG&A 費用所抵消。本季度營業收入佔收入的百分比為 27%，反映出收購的知識產權與研發費用造成約 115 個基點的負面影響。

Our Q2 effective tax rate was 16.1%. This represents an increase of 190 basis points compared to the same period in 2022 driven by the impact of the new Puerto Rico tax regime in the sales of rights for Baqsimi. At the bottom line, we delivered earnings per share of $2.11 in Q2, a 69% increase versus Q2 of 2022, inclusive of $0.43 of EPS associated with the sales of rights for Baqsimi.

我們第二季度的有效稅率為 16.1%。由於波多黎各新稅制對 Baqsimi 權利銷售的影響，與 2022 年同期相比增加了 190 個基點。從底線來看，我們第二季度的每股收益為 2.11 美元，與 2022 年第二季度相比增長了 69%，其中包括與 Baqsimi 權利銷售相關的 0.43 美元每股收益。

On Slide 8, we quantify the effect of price, rate and volume on revenue growth. This quarter, U.S. revenue increased 41%. When excluding revenue from COVID-19 antibodies and Baqsimi, U.S. revenue grew 30% driven by robust growth from Mounjaro, Verzenio and Jardiance. Net price in the U.S. increased 2% for the quarter driven by Mounjaro access and savings cards dynamics. Excluding Mounjaro, net price in the U.S. decreased by low single digits, consistent with prior trends.

在幻燈片 8 中，我們量化了價格、費率和數量對收入增長的影響。本季度，美國收入增長 41%。排除來自 COVID-19 抗體和 Baqsimi 的收入後，在 Mounjaro、Verzenio 和 Jardiance 強勁增長的推動下，美國收入增長了 30%。受 Mounjaro 准入卡和儲蓄卡動態的推動，本季度美國的淨價格增長了 2%。不包括Mounjaro，美國的淨價下降了低個位數，與之前的趨勢一致。

As I mentioned in our Q1 earnings call, we expect Mounjaro access and saving cards dynamics to have an even greater effect on reported U.S. price changes in the second half of this year.

正如我在第一季度財報電話會議中提到的，我們預計 Mounjaro 准入卡和儲蓄卡的動態將對今年下半年報告的美國價格變化產生更大的影響。

Europe continued its growth trajectory with revenue in Q2 up 6% in constant currency driven primarily by volume growth for Verzenio, Jardiance and Taltz. Volume in Europe increased 12% in the second quarter. For Japan, Q2 revenue increased 7% in constant currency as we continue to see robust growth in our newer medicine, led by Verzenio, and to a lesser extent, Jardiance, Olumiant and Mounjaro, the last of which launched in Japan in April.

歐洲繼續保持增長勢頭，第二季度收入按固定匯率計算增長了 6%，這主要得益於 Verzenio、Jardiance 和 Taltz 銷量增長。第二季度歐洲銷量增長 12%。在日本，按固定匯率計算，第二季度收入增長了7%，因為我們繼續看到以Verzenio 為首的新藥強勁增長，Jardiance、Olumiant 和Mounjaro（後者於4 月份在日本推出）的增長幅度較小。

Moving to China. Revenue increased 20% in constant currency with volume growth only minimally offset by price declines. Volume growth in Q2 was driven by Tyvyt and Verzenio. We are pleased to see our China business return to growth. Revenue in the rest of the world increased 19% in constant currency as volume growth of 20% was driven by Mounjaro, Verzenio and Jardiance.

搬到中國。按固定匯率計算，收入增長了 20%，但銷量增長僅被價格下降所抵消。第二季度銷量增長由達伯舒 (Tyvyt) 和 Verzenio 推動。我們很高興看到我們的中國業務恢復增長。按固定匯率計算，世界其他地區的收入增長了 19%，Mounjaro、Verzenio 和 Jardiance 推動銷量增長 20%。

Slide 9 shows the contribution to worldwide volume growth by product category. As you may recall on our Q1 earnings call, we simplified the categorization of our products with a focus on 2 categories: new products and growth products. As you can see, the new and growth categories combined contributed 26 percentage points of volume growth for the quarter. The volume growth for all others category was driven by the sale of rights to Baqsimi. The lack of revenue from COVID-19 antibodies compared to the base period was a milder headwind to growth in Q2 compared to Q1 and will continue to be a modest impact to prior year comparisons.

幻燈片 9 按產品類別顯示了對全球銷量增長的貢獻。您可能還記得在我們第一季度的財報電話會議上，我們簡化了產品的分類，重點關注兩類：新產品和成長產品。正如您所看到的，新類別和增長類別合計為本季度銷量增長貢獻了 26 個百分點。所有其他類別的銷量增長都是由 Baqsimi 的權利出售推動的。與基期相比，COVID-19 抗體收入的缺乏對第二季度的增長造成的阻力較第一季度溫和，並且與上一年相比仍將產生適度的影響。

Slide 10 provides additional perspectives across our product categories. I'll speak more about Mounjaro shortly but first, let me highlight the continued outstanding performance of Verzenio, which saw worldwide sales growth of 57% in Q2 as OUS volume grew 82%, while U.S. volume grew 47%. Jardiance also continued its strong performance with worldwide sales growth of 45% for the quarter.

幻燈片 10 提供了我們產品類別的更多視角。我很快就會更多地談論Mounjaro，但首先讓我強調一下Verzenio 持續出色的表現，該公司第二季度的全球銷售額增長了57%，其中OUS 銷量增長了82%，而美國銷量增長了47%。 Jardiance 也繼續保持強勁業績，本季度全球銷售額增長 45%。

There have been 2 notable regulatory approval for Jardiance in the last 2 months. In June, the FDA approved Jardiance for the treatment of type 2 diabetes in children 10 years and older, making Jardiance the first and only SGLT2 inhibitor approved for this patient population. And in late July, Jardiance was approved in the EU for the treatment of adults with chronic kidney disease. After almost a decade on the market, Jardiance continues to demonstrate its importance to patients across a number of cardiorenal metabolic conditions.

過去 2 個月，Jardiance 獲得了 2 項值得注意的監管批准。 6 月，FDA 批准 Jardiance 用於治療 10 歲及以上兒童的 2 型糖尿病，使 Jardiance 成為第一個也是唯一一個被批准用於該患者群體的 SGLT2 抑製劑。 7 月下旬，Jardiance 在歐盟獲得批准用於治療成人慢性腎病。上市近十年後，Jardiance 繼續證明其對多種心腎代謝疾病患者的重要性。

Trulicity performance has held up well in a growing and dynamic incretin market. In Q2, we saw worldwide Trulicity revenue decline by 5% as modest volume growth was more than offset by price erosion. In international markets, Trulicity volume continues to be affected by measures we have taken to minimize potential disruption to existing patients, including communications to health care professionals not to initiate patients on Trulicity. We remain confident that Trulicity will continue to be an important option for HCPs and patients in years to come.

Trulicity 的性能在不斷增長且充滿活力的腸促胰島素市場中保持良好。第二季度，我們看到 Trulicity 全球收入下降了 5%，因為銷量的溫和增長被價格侵蝕所抵消。在國際市場，Trulicity 的銷量繼續受到我們為盡量減少對現有患者的潛在干擾而採取的措施的影響，包括與醫療保健專業人員溝通，不要讓患者開始使用 Trulicity。我們仍然相信 Trulicity 在未來幾年將繼續成為 HCP 和患者的重要選擇。

Moving to Slide 11. I will share some perspective on Mounjaro's performance. We continue to be pleased with the strong momentum of Mounjaro as more type 2 diabetes patients benefit from the medicine. Mounjaro's revenue in the U.S. grew to $960 million for the quarter. In Q2, we continued to make progress in expanding access to Mounjaro, and access reached 73% on July 1 for patients with type 2 diabetes across commercial and Part D. We estimate that the percentage of paid scripts from Mounjaro in Q2 was approximately 67%, up from approximately 55% in Q1.

轉到幻燈片 11。我將分享對 Mounjaro 表現的一些看法。隨著越來越多的 2 型糖尿病患者受益於該藥物，我們仍然對 Mounjaro 的強勁勢頭感到高興。本季度 Mounjaro 在美國的收入增長至 9.6 億美元。在第二季度，我們在擴大Mounjaro 的使用方面繼續取得進展，7 月1 日，商業版和D 部分的2 型糖尿病患者的使用率達到了73%。我們估計第二季度來自Mounjaro 的付費腳本的百分比約為67% ，高於第一季度的約 55%。

As a reminder, we define paid scripts as those prescriptions outside of the $25 noncovered co-pay card but inclusive of the $25 covered co-pay card. Since the $25 noncovered co-pay card program expired in June 30, we would expect the proportion of paid script next quarter to be 100% under this definition.

提醒一下，我們將付費處方定義為 25 美元非承保自付卡之外但包含 25 美元承保自付卡的處方。由於 25 美元的非承保共付卡計劃已於 6 月 30 日到期，因此我們預計下季度的付費腳本比例在此定義下為 100%。

Looking forward to the rest of the year, we expect continued growth in new-to-brand prescription as well as ongoing improvement in access.

展望今年剩餘時間，我們預計新品牌處方將持續增長，並且可及性將持續改善。

Lastly, regarding the demand and supply outlook for incretin. We're pleased that commercial production has started at our RTP site in North Carolina. Even as we ramp up capacity at RTP, we believe supply will likely remain tight in the coming months and quarters due to significant demand.

最後，關於腸促胰島素的需求和供應前景。我們很高興北卡羅來納州的 RTP 工廠已經開始商業化生產。即使我們提高 RTP 的產能，我們相信由於需求旺盛，未來幾個月和幾個季度供應可能仍將緊張。

Given the expected global demand for tirzepatide, as we mentioned on previous earnings call, we are moving forward with different presentations to bring tirzepatide to more patients faster. To this end, we initiated a bioequivalent study in early April for a multi-dose quick pen device. In many OUS markets, we expect to launch tirzepatide first in valve form later this year and transition to a multi-dose quick pen as approved and available in these markets starting in 2024. The launch of the valve and quick pen presentations for tirzepatide will leverage existing manufacturing assets and capacity. We're excited about the opportunity to expand the number of people we can help in the short term and long term with these additional options.

鑑於全球對替澤帕肽的預期需求，正如我們在之前的財報電話會議上提到的，我們正在推進不同的演示，以更快地將替澤帕肽帶給更多患者。為此，我們於四月初啟動了一項多劑量快速筆裝置的生物等效性研究。在許多OUS 市場，我們預計將在今年晚些時候首先以閥門形式推出替澤帕肽，並從2024 年開始過渡到這些市場批准並上市的多劑量快速筆。替澤帕肽的閥門和快速筆演示的推出將利用現有的製造資產和能力。我們很高興有機會通過這些額外的選擇來擴大我們可以在短期和長期幫助的人數。

On Slide 12, we provide an update on capital allocation. In the first 6 months of 2023, we invested $5.7 billion in our future growth through a combination of R&D expenditures, capital investments and business development outlays. In addition, we returned nearly $2.8 billion to shareholders in dividends and share repurchases.

在幻燈片 12 中，我們提供了資本配置的最新情況。 2023 年前 6 個月，我們通過研發支出、資本投資和業務發展支出相結合，為未來增長投資了 57 億美元。此外，我們還通過股息和股票回購向股東返還了近 28 億美元。

Slide 3 (sic) [Slide 13] presents our updated 2023 financial guidance. Given the strong performance in our underlying business as well as revenue from the sales of rights for Baqsimi and olanzapine, we are increasing our 2023 revenue guidance by $2.2 billion to a range of $33.4 billion to $33.9 billion. Approximately $1.5 billion of this increase is driven by business development activities, including the sales of rights for the olanzapine portfolio and Baqsimi, while the remainder reflects strong underlying business performance.

幻燈片 3（原文如此）[幻燈片 13] 介紹了我們更新的 2023 年財務指引。鑑於我們基礎業務的強勁表現以及 Baqsimi 和奧氮平權利銷售的收入，我們將 2023 年的收入指導上調 22 億美元，達到 334 億美元至 339 億美元的範圍。其中約 15 億美元的增長是由業務開發活動推動的，包括出售奧氮平產品組合和 Baqsimi 的權利，而其餘部分則反映了強勁的基礎業務業績。

Our updated FX assumptions based on recent spot rates are listed and represents a de minimis impact to the updated guidance. Our guidance for gross margin as a percent of revenue has increased to approximately 80% driven by the sales of rights for Baqsimi and our olanzapine portfolio.

我們根據近期即期匯率更新了外匯假設，這對更新後的指導產生了微乎其微的影響。由於 Baqsimi 和我們的奧氮平產品組合的權利銷售，我們對毛利率佔收入百分比的指導已增加至約 80%。

We're also increasing the range of operating expense guidance for the year. Marketing, selling and administrative costs are now expected to be in the range of $7.2 billion to $7.4 billion with the increase driven by additional investments in recent launches in preparation for launches of new medicine and line extensions expected later this year.

我們還擴大了今年運營費用指導的範圍。目前，營銷、銷售和管理成本預計將在72 億至74 億美元之間，這一增長是由於最近推出的額外投資所推動的，這些投資是為今年晚些時候推出新藥和產品線擴展做準備的。

The range for research and development expenses has been increased to $8.9 billion to $9.1 billion, reflecting positive dynamics across our portfolio, including success in events in our early-stage assets, positive enrollment trends in our late-stage studies, broadening of the clinical program for next-generation incretin, and expected incremental expenses from business development activities.

研發費用範圍已增加至 89 億美元至 91 億美元，反映了我們整個投資組合的積極動態，包括我們早期資產活動的成功、我們後期研究的積極入組趨勢、臨床項目的擴大下一代腸促胰素，以及業務開發活動的預期增量費用。

We have incorporated IPR&D charges that have been incurred through Q2 2023, which totaled $202 million. Other income and expense and tax rate guidance have also been updated. OID is now expected to be between $0 million and $100 million in income, up from prior guidance of $100 million to $200 million in expense. We've also increased our estimated effective tax rate to be in the range of 14% to 15%, up from approximately 13%, reflecting the impact of the sales of rights for our olanzapine portfolio and Baqsimi.

我們已納入截至 2023 年第二季度產生的知識產權與研發費用，總計 2.02 億美元。其他收入和支出以及稅率指導也已更新。 OID 目前預計收入為 000 萬至 1 億美元，高於之前指導的 1 億至 2 億美元支出。我們還將估計有效稅率從大約 13% 提高到 14% 至 15%，反映了出售我們的奧氮平產品組合和 Baqsimi 權利的影響。

Based on these changes, we have raised our full year reported EPS guidance to now be in the range of $9.20 to $9.40 per share and raised our non-GAAP EPS guidance to be in the range of $9.70 to $9.90.

基於這些變化，我們將全年報告的每股收益指導提高至每股 9.20 美元至 9.40 美元，並將非 GAAP 每股收益指導提高至 9.70 美元至 9.90 美元。

Now I will turn the call over to Dan to highlight our progress in R&D.

現在我將把電話轉給 Dan，強調我們在研發方面的進展。

Thanks, Anat. It's been a productive and busy few months for Lilly R&D. Since our last earnings call, we've had a few major readouts across our therapeutic areas, and we've announced several business development transactions. Let me start with the data that we shared in June at the American Diabetes Association. We presented over 40 abstracts across our portfolio and shared data during 2 ADA-sponsored symposia.

謝謝，阿納特。對於禮來公司的研發來說，這幾個月是富有成效且忙碌的幾個月。自上次財報電話會議以來，我們在治療領域獲得了一些重要數據，並且宣布了幾項業務開發交易。讓我從我們六月份在美國糖尿病協會分享的數據開始。我們在 ADA 贊助的 2 場研討會上展示了 40 多份關於我們的投資組合的摘要並共享了數據。

The first was for the Phase III results from the SURMOUNT-2 study of tirzepatide in adults with obesity or overweight in type 2 diabetes, which was simultaneously published in the New England Journal of Medicine. And the second symposium was for the results from 2 Phase II trials of retatrutide, our GIP/GLP glucagon tri-agonist in adults with obesity and overweight as well as in people with type 2 diabetes. The retatrutide results in obesity and type 2 diabetes were simultaneously published in New England Journal of Medicine and Lancet, respectively.

第一個是替西帕肽治療成人肥胖或超重 2 型糖尿病患者的 SURMOUNT-2 研究的 III 期結果，該研究同時發表在《新英格蘭醫學雜誌》上。第二次研討會的主題是瑞他魯肽的兩項II 期試驗的結果，瑞他魯肽是我們的GIP/GLP 胰高血糖素三激動劑，用於治療成人肥胖和超重以及2 型糖尿病患者。瑞他魯肽治療肥胖和2型糖尿病的結果分別同時發表在《新英格蘭醫學雜誌》和《柳葉刀》上。

We also shared an oral presentation on our Phase II trial results for orforglipron, our once-daily, non-peptide oral GLP-1 in adults with obesity or overweight. These results were simultaneously published in New England Journal. We also presented results from a Phase II trial of orforglipron in patients with type 2 diabetes, and these were published in the Lancet. Clearly, we're proud of all of this data in diabetes and obesity portfolio.

我們還分享了關於 orforglipron 的 II 期試驗結果的口頭報告，orforglipron 是我們每天一次的非肽口服 GLP-1，用於治療肥胖或超重的成人。這些結果同時發表在《新英格蘭雜誌》上。我們還介紹了 orforglipron 在 2 型糖尿病患者中進行的 II 期試驗的結果，這些結果發表在《柳葉刀》上。顯然，我們對糖尿病和肥胖症組合中的所有這些數據感到自豪。

Since we discussed the top line data for SURMOUNT-2 tirzepatide trial during our last earnings call, I'll focus my updates today on the Phase II data shared for orforglipron and retatrutide, starting with orforglipron on Slide 14. The orforglipron presentation highlighted safety and efficacy data across 6 dose arms in our Phase II study in obesity. With an overall mean body weight at baseline of 109 kilograms, orforglipron demonstrated an average of up to 14.7% body weight reduction at 36 weeks.

由於我們在上次財報電話會議期間討論了SURMOUNT-2 tirzepatide 試驗的主要數據，因此我今天的更新重點是orforglipron 和瑞他魯肽共享的II 期數據，從幻燈片14 上的orforglipron 開始。orforglipron 的演示強調了安全性和我們的肥胖 II 期研究中 6 個劑量組的療效數據。 Orforglipron 的基線總體平均體重為 109 公斤，36 週時體重平均減輕了 14.7%。

At the second highest dose tested in the study, 75% of participants reached a weight reduction goal of 10% or more. We also shared data showing a dose-dependent decrease in systolic blood pressure and an overall improvement in lipid levels. The most common adverse events were GI-related and generally occurred earlier in the trial during the titration phase and were mostly mild to moderate. While we've not yet shared the dosing details for our Phase III studies, these Phase II results have informed our approach on dose escalation.

在研究中測試的第二高劑量下，75% 的參與者達到了 10% 或更多的體重減輕目標。我們還分享了數據，顯示收縮壓呈劑量依賴性下降，血脂水平總體改善。最常見的不良事件與胃腸道相關，通常發生在試驗早期滴定階段，且大多為輕度至中度。雖然我們尚未分享 III 期研究的劑量細節，但這些 II 期研究結果已經為我們劑量遞增的方法提供了信息。

We also presented data at ADA from a similar Phase II study of orforglipron in people with type 2 diabetes, the results of which are highlighted on Slide 15. Orforglipron demonstrated a mean reduction in hemoglobin A1c at 26 weeks of up to 2.1%, and over 90% of participants on the highest 3 doses achieved A1c levels less than 7%. We initiated Phase III trials for orforglipron in both obesity and type 2 diabetes in the second quarter, and we look forward to those results in 2025.

我們還在 ADA 上展示了 Orforglipron 在 2 型糖尿病患者中進行的一項類似 II 期研究的數據，其結果在幻燈片 15 中突出顯示。Orforglipron 證明，26 週時血紅蛋白 A1c 平均降低高達 2.1%，超過接受最高3 劑劑量的參與者中有90% 的A1c 水平低於7%。我們在第二季度啟動了 orforglipron 治療肥胖和 2 型糖尿病的 III 期試驗，我們期待在 2025 年獲得這些結果。

For retatrutide, the full results of 2 Phase II trials were presented during an ADA-sponsored symposium, which discussed efficacy and safety in adults with obesity or overweight with at least one weight-related comorbidity as well as in people with type 2 diabetes. There's also a segment of the symposium focused on liver fat and NASH-related biomarker data in patients with nonalcoholic fatty liver disease, which showed relative liver fat reduction of over 80% at 24 weeks for the [2] is doses.

對於瑞他魯肽，2 項II 期試驗的完整結果在ADA 主辦的研討會上公佈，該研討會討論了瑞他魯肽對患有至少一種與體重相關的合併症的肥胖或超重成人以及2 型糖尿病患者的療效和安全性。研討會還有一個部分重點關注非酒精性脂肪肝患者的肝臟脂肪和 NASH 相關生物標誌物數據，結果顯示，在 [2] 劑量下，24 週時相對肝臟脂肪減少了 80% 以上。

Slide 16 highlights key results from the obesity Phase II trial in which retatrutide met the primary end point at 24 weeks, demonstrating mean weight reduction up to 17.5%. The safety profile of retatrutide was similar to other incretin-based therapies. In a secondary end point of weight reduction at 48 weeks, participants treated with the highest dose of retatrutide demonstrated a mean rate -- weight reduction up to 24.2% or almost 58 pounds on average.

幻燈片 16 重點介紹了肥胖 II 期試驗的主要結果，其中瑞他魯肽在 24 週時達到了主要終點，表明平均體重減輕高達 17.5%。瑞他魯肽的安全性與其他基於腸降血糖素的療法相似。在 48 週時體重減輕的次要終點中，接受最高劑量瑞他魯肽治療的參與者表現出平均體重減輕高達 24.2% 或平均近 58 磅。

If confirmed in registrational trials, we believe that magnitude of mean weight reduction would represent a new high watermark for weight loss from a pharmacologic agent at this time point. It's also worth noting that the Phase II retatrutide trial in obesity was well balanced between genders with females representing just under half of all participants in the trial. This was intentional and is atypical for incretin clinical trials in obesity, which often have a higher proportion of female participants, a subgroup that typically experiences greater weight loss than males.

如果在註冊試驗中得到證實，我們相信平均體重減輕的幅度將代表此時藥物製劑體重減輕的新高水位。還值得注意的是，瑞他魯肽治療肥胖症的 II 期試驗在性別之間取得了很好的平衡，女性僅佔試驗所有參與者的一半以下。這是故意的，對於肥胖症的腸促胰素臨床試驗來說是非典型的，這些臨床試驗通常有較高比例的女性參與者，這個亞組通常比男性經歷更多的體重減輕。

Indeed, in the retatrutide Phase II obesity trial, the mean change in body weight for female participants at the highest dose was 28.5%. Given these encouraging results, we moved rapidly to initiate the Triumph Phase III program, which will evaluate the safety and efficacy of retatrutide for chronic weight management, obstructive sleep apnea and knee osteoarthritis in people with overweight and obesity. These 4 Phase III trials will each run between 68 and 80 weeks. The trajectory of weight loss seen in the Phase II study reinforces our belief that retatrutide can potentially represent a further improvement and additional option for patients seeking pharmacological treatment for obesity and its complications.

事實上，在瑞他魯肽 II 期肥胖試驗中，最高劑量的女性參與者體重平均變化為 28.5%。鑑於這些令人鼓舞的結果，我們迅速啟動了Triumph III 期計劃，該計劃將評估瑞他魯肽治療超重和肥胖人群的慢性體重管理、阻塞性睡眠呼吸暫停和膝骨關節炎的安全性和有效性。這 4 項 III 期試驗將分別持續 68 至 80 週。 II 期研究中看到的體重減輕軌跡強化了我們的信念，瑞他魯肽可能代表著尋求藥物治療肥胖及其並發症的患者的進一步改善和額外選擇。

While retatrutide's Phase II results in obesity garnered much attention at ADA, the Phase II results in patients with type 2 diabetes are also very encouraging with participants receiving retatrutide achieving a hemoglobin A1c reduction of up to 2% on average in addition to meaningful levels of weight loss. I'm pleased to share that we plan to advance retatrutide into Phase III for type 2 diabetes.

雖然瑞他魯肽在肥胖方面的II 期結果在ADA 引起了廣泛關注，但在2 型糖尿病患者中的II 期結果也非常令人鼓舞，接受瑞他魯肽的參與者除了有意義的體重水平外，血紅蛋白A1c 平均降低了高達2%損失。我很高興地告訴大家，我們計劃將瑞他魯肽推進到治療 2 型糖尿病的 III 期臨床。

Moving to tirzepatide on Slide 17. We were delighted to announce in late July that SURMOUNT-3 and SURMOUNT-4 trials of tirzepatide in obesity met all primary and key secondary objectives. In key secondary objectives for both these studies, participants achieved similar mean weight reduction, 26.6% in SURMOUNT-3 and 26.0% in SURMOUNT-4. While these 2 trials were not required for our chronic weight management submission to the FDA, they provide important additional information regarding the role tirzepatide plays in maintaining or adding to the weight loss achieved with either intensive lifestyle intervention or pharmacotherapy in adults living with obesity or overweight.

轉到幻燈片 17 上的替澤帕肽。我們很高興在 7 月下旬宣布，替澤帕肽治療肥胖症的 SURMOUNT-3 和 SURMOUNT-4 試驗達到了所有主要和關鍵的次要目標。在這兩項研究的關鍵次要目標中，參與者實現了類似的平均體重減輕，SURMOUNT-3 中為 26.6%，SURMOUNT-4 中為 26.0%。雖然這兩項試驗不需要我們向FDA 提交長期體重管理報告，但它們提供了關於替西帕肽在維持或增加肥胖或超重成年人通過強化生活方式乾預或藥物治療實現的體重減輕方面所發揮的作用的重要附加信息。

SURMOUNT-3 evaluated tirzepatide following an intensive lifestyle modification program and demonstrated that even in people who have a weight loss response to lifestyle intervention, tirzepatide provides significant additional weight loss. SURMOUNT-4 was a randomized withdrawal study in which all participants received tirzepatide for a 36-week lead-in period, at which point, half the participants were switched to placebo and the other half continued treatment with tirzepatide. This study demonstrated that those participants who continued on tirzepatide experienced continued weight loss, while those who switched to placebo started to regain weight.

SURMOUNT-3 在強化生活方式改變計劃後評估了替澤帕肽，並證明即使對於對生活方式乾預有減肥反應的人來說，替澤帕肽也能提供顯著的額外減肥效果。 SURMOUNT-4 是一項隨機退出研究，其中所有參與者均接受 tirzepatide 為期 36 週的導入期，此時一半參與者轉為安慰劑，另一半繼續接受 tizepatide 治療。這項研究表明，那些繼續服用替西帕肽的參與者體重持續減輕，而那些改用安慰劑的參與者體重開始反彈。

These data reinforce our understanding that obesity is a complex chronic disease for which multiple treatment approaches, including lifestyle modification and effective medications, are needed. We believe tirzepatide is well positioned to be one such treatment option. Accordingly, we submitted an application for tirzepatide for chronic weight management to the FDA during Q2. The FDA granted this application priority review designation, and we anticipate FDA action by year-end.

這些數據加深了我們的認識，即肥胖是一種複雜的慢性疾病，需要多種治療方法，包括改變生活方式和有效的藥物治療。我們相信替西帕肽很適合成為此類治療選擇之一。因此，我們在第二季度向 FDA 提交了用於長期體重管理的替西帕肽申請。 FDA 授予了該申請優先審查資格，我們預計 FDA 將在年底前採取行動。

Slide 18 shows select pipeline opportunities as of August 4, and Slide 19 shows potential key events for the year. I've covered the major updates in diabetes, including the advancement of orforglipron and retatrutide into Phase III since our learning -- last earnings call.

幻燈片 18 顯示了截至 8 月 4 日的精選管道機會，幻燈片 19 顯示了今年潛在的關鍵事件。我介紹了糖尿病領域的重大進展，包括自上次財報電話會議以來，orforglipron 和瑞他魯肽進入 III 期臨床試驗。

Turning then to our neuroscience portfolio. 3 weeks ago with the AIC meeting in Amsterdam and simultaneously published in JAMA, we were excited to share the detailed results from the TRAILBLAZER-ALZ 2 study, highlighting donanemab's robust efficacy profile across a number of new analyses that reinforce our belief in the medicine's ability to meaningfully slow the progression of Alzheimer's disease, especially in patients earlier in disease progression. We cover the results in some detail during our AIC investor call so I won't cover that again, except to note that we submitted donanemab to the FDA and to the EMA for approval, and we look forward to FDA action before the end of this year.

然後轉向我們的神經科學產品組合。 3 週前，在阿姆斯特丹舉行的AIC 會議上，我們很高興地分享了TRAILBLAZER-ALZ 2 研究的詳細結果，並在《JAMA》上同時發表，這些結果強調了多南單抗在多項新分析中的強大功效，這些分析增強了我們對該藥物能力的信心有意義地減緩阿爾茨海默病的進展，特別是對於疾病進展早期的患者。我們在AIC 投資者電話會議上詳細介紹了結果，因此我不會再介紹這一點，只是要指出，我們已向FDA 和EMA 提交了多南單抗以供批准，我們期待FDA 在本次會議結束前採取行動年。

Shifting to oncology. Launch progress continues with Jaypirca and mantle cell lymphoma, and we are pleased to have the detailed chronic lymphocytic leukemia results from the BRUIN Phase I/II trial published in New England Journal in early July. Following the discussion with the FDA, we've now submitted an application for accelerated approval for Jaypirca in CLL patients previously treated with both a covalent BTK inhibitor and venetoclax based on the results from the BRUIN Phase I/II study. We expect FDA action by year-end.

轉向腫瘤學。 Jaypirca 和套細胞淋巴瘤的啟動進展仍在繼續，我們很高興看到 7 月初在《新英格蘭雜誌》上發表的 BRUIN I/II 期試驗的詳細慢性淋巴細胞白血病結果。經過與 FDA 的討論，我們現在根據 BRUIN I/II 期研究的結果提交了一份申請，加速批准 Jaypirca 用於先前接受共價 BTK 抑製劑和 Venetoclax 治療的 CLL 患者。我們預計 FDA 將在年底前採取行動。

Also during the quarter, we completed the regulatory submission in Japan for pirtobrutinib for patients with MCL. We continue to study pirtobrutinib in multiple Phase III trials and look forward to the results from the BRUIN 321 trial in CLL, which we now expect to see before the end of this year, and it has been added to our key events slide.

同樣在本季度，我們在日本完成了 pirtobrutinib 用於 MCL 患者的監管提交。我們繼續在多個 III 期試驗中研究 pirtobrutinib，並期待 CLL 中的 BRUIN 321 試驗的結果，我們現在預計在今年年底之前看到該結果，並且它已添加到我們的關鍵事件幻燈片中。

In other oncology developments, at ASCO in June, we presented new data from the Verzenio monarchE trial in high-risk early breast cancer. For the first time, we showed data demonstrating the efficacy of the medicine in this setting is not compromised when patients undergo dose reductions. We believe that the ability to manage Verzenio's side effects while preserving efficacy could be very important to ensuring that patients complete their 2 years of therapy. This is an emerging part of Verzenio's differentiation in this class.

在其他腫瘤學進展中，我們在 6 月份的 ASCO 上展示了 Verzenio MonarchE 試驗在高風險早期乳腺癌中的新數據。我們首次展示的數據表明，當患者減少劑量時，藥物在這種情況下的療效不會受到影響。我們相信，在保持療效的同時控制 Verzenio 副作用的能力對於確保患者完成 2 年的治療非常重要。這是 Verzenio 在同類產品中脫穎而出的一個新興部分。

We're also very excited about last week's announcement regarding the randomized trial of Retevmo in treatment-naive RET fusion-positive lung cancer. As we communicated in the press release, this randomized trial was declared successful on its primary end point of progression-free survival, the first time any targeted therapy in lung cancer has ever shown superiority to a PD-1 plus chemotherapy regimen. While we remain disappointed by the low levels of genomic profiling done at the time of lung cancer diagnosis, we're hopeful that these data will continue to advance the practice of genomic-driven medicine. We look forward to sharing the full results of the study at an upcoming medical meeting.

我們也對上周宣布的有關 Retevmo 治療初治 RET 融合陽性肺癌的隨機試驗感到非常興奮。正如我們在新聞稿中所傳達的那樣，這項隨機試驗在其主要終點無進展生存期上被宣布成功，這是肺癌靶向治療首次顯示出優於 PD-1 加化療方案的優勢。雖然我們對肺癌診斷時基因組分析的低水平仍然感到失望，但我們希望這些數據將繼續推進基因組驅動醫學的實踐。我們期待在即將召開的醫學會議上分享該研究的全部結果。

In our earlier-stage oncology portfolio, the combination experiment of our KRAS G12C inhibitor with pembrolizumab continues to mature nicely. And we're now working to initiate Phase III trials in first-line G12C-mutated lung cancer in the next 6 to 9 months.

在我們的早期腫瘤學產品組合中，我們的 KRAS G12C 抑製劑與 pembrolizumab 的聯合實驗繼續成熟。我們現在正致力於在未來 6 至 9 個月內啟動針對一線 G12C 突變肺癌的 III 期試驗。

More broadly, we're excited to see the overall progress of our oncology portfolio. In addition to last week's Retevmo announcement, we expect another 7 randomized trial readouts in 4 to 6 new first-in-human trials across small molecules and biologics in oncology over the next 12 months. With the acquisition of Loxo Oncology 4 years ago, we catalyzed a change in the strategy and direction of oncology at Lilly, and we're seeing the fruits of these efforts.

更廣泛地說，我們很高興看到我們的腫瘤學產品組合的整體進展。除了上週的 Retevmo 公告之外，我們預計未來 12 個月內將有 4 至 6 項新的針對腫瘤學小分子和生物製劑的首次人體試驗中的 7 項隨機試驗結果。四年前收購 Loxo Oncology 後，我們促進了禮來公司腫瘤學戰略和方向的變革，我們正在看到這些努力的成果。

Finally, in immunology, we have several updates related to mirikizumab. A Digestive Disease Week in May, we presented new analyses from the Phase III LUCENT-1 and LUCENT-2 studies, demonstrating that remission of key symptoms of ulcerative colitis, including bowel urgency, was associated with significant improvement in the quality-of-life assessment in adults with UC.

最後，在免疫學方面，我們有一些與 mirikizumab 相關的更新。在五月的消化疾病周中，我們展示了 III 期 LUCENT-1 和 LUCENT-2 研究的新分析，表明潰瘍性結腸炎的關鍵症狀（包括腸急迫感）的緩解與生活質量的顯著改善相關成人UC 的評估。

In Q2, we launched mirikizumab marketed as Omvoh in Japan as a treatment for adults with moderately to severe active UC. In late May, we received approval for Onvio in the EU and have subsequently launched Omvoh in Germany and planned additional launches in the EU later this year.

在第二季度，我們推出了 mirikizumab，在日本以 Omvoh 名義上市，用於治療成人中度至重度活動性 UC。 5 月底，我們在歐盟獲得了 Onvio 的批准，隨後在德國推出了 Omvoh，併計劃今年晚些時候在歐盟推出更多產品。

In the U.S., we've resubmitted our application to the FDA. We now expect regulatory action by the end of this year. For lebrikizumab, our IL-13 monoclonal antibody under regulatory review for atopic dermatitis, we presented a new secondary analysis at the Revolutionizing Atopic Dermatitis Conference in May. This post-hoc analysis demonstrated improvement or clearance of face or hand dermatitis in adult and adolescent patients treated with lebrikizumab. These are parts of the body that are highly visible and for which dermatitis can be particularly burdensome and stigmatizing. We expect regulatory action for lebrikizumab in both the U.S. and EU later this year. Together with Almirall, our development and commercialization partner in Europe, we look forward to potentially bringing this important medicine to patients who suffer from this chronic disease.

在美國，我們已向 FDA 重新提交了申請。我們現在預計在今年年底之前採取監管行動。對於 lebrikizumab（我們正在針對特應性皮炎進行監管審查的 IL-13 單克隆抗體），我們在 5 月份的革命性特應性皮炎會議上提出了新的二級分析。這項事後分析表明，接受 lebrikizumab 治療的成人和青少年患者的面部或手部皮炎得到改善或清除。這些身體部位非常明顯，皮炎對這些部位來說尤其造成負擔和恥辱。我們預計美國和歐盟將於今年晚些時候對 lebrikizumab 採取監管行動。我們期待與我們在歐洲的開發和商業化合作夥伴 Almirall 一起，將這種重要的藥物帶給患有這種慢性病的患者。

Looking earlier in our immunology pipeline, we're pleased in May to have the detailed results from our Phase IIa study of peresolimab in rheumatoid arthritis published in the New England Journal. These data were first presented as a late-breaking abstract at the American College of Rheumatology Annual Meeting in late 2022 and represent the first clinical evidence that's stimulating the endogenous PD-1 inhibitory pathway could be an effective approach to treat rheumatologic disease. As you can see, Q2 was another productive quarter for Lilly R&D with important progress in each of our therapeutic areas.

回顧我們的免疫學研究進展，我們很高興在 5 月份在《新英格蘭雜誌》上發表了佩雷索利單抗治療類風濕性關節炎的 IIa 期研究的詳細結果。這些數據首次在 2022 年底的美國風濕病學會年會上作為最新摘要提出，代表了刺激內源性 PD-1 抑制途徑可能成為治療風濕病的有效方法的第一個臨床證據。正如您所看到的，第二季度是禮來研發部門另一個富有成效的季度，我們在每個治療領域都取得了重要進展。

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

現在我將把電話轉回給戴夫，讓他作結束語。

Thank you, Dan. Before we go to Q&A, let me briefly sum up our progress in the second quarter. This quarter saw an acceleration of revenue growth as our recently launched product portfolio gathers momentum. Excluding COVID-19 antibodies and Baqsimi revenue, we grew 22% driven by Mounjaro, Verzenio and Jardiance.

謝謝你，丹。在進行問答之前，我先簡單總結一下我們第二季度的進展。隨著我們最近推出的產品組合蓄勢待發，本季度收入增長加速。不包括 COVID-19 抗體和 Baqsimi 收入，在 Mounjaro、Verzenio 和 Jardiance 的推動下，我們增長了 22%。

The quarter also saw a continuation of investment in our future growth in our manufacturing expansion, in late-stage medicines, in early phase capabilities and in business development. Notwithstanding these long-term investments, we continue to expect our revenue will grow more rapidly than our expense base in the coming years and see significant opportunity for margin expansion.

本季度我們還繼續對製造擴張、後期藥物、早期能力和業務發展的未來增長進行投資。儘管有這些長期投資，我們仍然預計未來幾年我們的收入增長將超過我們的支出基礎，並看到利潤率擴張的重大機會。

We also achieved meaningful advances in our near-term pipeline with positive phase -- positive top line results, detailed data disclosures and submission of donanemab for traditional approval to the FDA and EMA, and completion of the tirzepatide submission in chronic weight management, alongside positive top line results from 2 more Phase III trials for the SURMOUNT program. We also shared data from 4 mid-stage clinical trials for orforglipron and retatrutide and initiated Phase III trials for both assets.

我們還在近期管道中取得了有意義的進展，並取得了積極的階段——積極的頂線結果、詳細的數據披露和向FDA 和EMA 提交多南單抗傳統批准，以及完成慢性體重管理中的替澤帕肽提交，同時積極的SURMOUNT 項目的另外 2 項 III 期試驗的頂線結果。我們還共享了奧福格列隆和瑞他魯肽的 4 項中期臨床試驗的數據，並啟動了這兩種資產的 III 期試驗。

Lastly, we announced several targeted business development moves intended to bolster our early- and mid-stage portfolio and our R&D capabilities, and we returned over $1 billion to shareholders via the dividend.

最後，我們宣布了幾項有針對性的業務發展舉措，旨在增強我們的早期和中期投資組合以及研發能力，並通過股息向股東返還超過 10 億美元。

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

現在我將把電話轉給喬來主持問答環節。

Thanks, Dave. We'd like to take questions from as many callers as possible and conclude our call in a timely manner. (Operator Instructions) We'll end the call at 10:15 a.m. (Operator Instructions)

謝謝，戴夫。我們希望回答盡可能多的來電者的問題並及時結束我們的通話。 （接線員說明）我們將於上午 10:15 結束通話（接線員說明）

Paul, please provide the instructions for the Q&A session, and then we're ready for the first caller.

Paul，請提供問答環節的說明，然後我們就準備好迎接第一個來電者。

(Operator Instructions) The first question today is coming from Louise Chen from Cantor.

（操作員說明）今天的第一個問題來自Cantor 的Louise Chen。

Just wanted to ask you about the Novo SELECT study that came out this morning. What kind of read-throughs do you see for the industry? And do you think it will help improve reimbursement for obesity/overweight drugs?

只是想詢問您有關今天早上發布的 Novo SELECT 研究的情況。您認為該行業有哪些類型的解讀？您認為這將有助於改善肥胖/超重藥物的報銷嗎？

Thanks, Louis. We'll go to Mike for that question on the recent SELECT news.

謝謝，路易斯。我們將就最近的 SELECT 新聞向 Mike 詢問這個問題。

Thanks, Louise. I assume we probably would get a question on the SELECT trial, and thanks for starting out the call with that. The SELECT trial read out as we expected. I think the results are great for the anti-obesity medication class. It should really support access for any payers who are on the fence of whether they should add anti-obesity medications or not.

謝謝，路易絲。我想我們可能會收到有關 SELECT 試驗的問題，感謝您以此開始通話。 SELECT 試驗的結果符合我們的預期。我認為抗肥胖藥物類別的結果非常好。它應該真正支持任何猶豫是否應該添加抗肥胖藥物的付款人的使用。

I think importantly, it should turn the conversation of the benefits of weight loss away from aesthetics and more toward the health benefit of people living with obesity. When you look overall, there are 236 obesity-related health complications. To name a few, obesity increases the risk of type 2 diabetes by 243%, coronary heart disease by 69%, hypertension by 113%, dyslipidemia by 74%. The overall cost of obesity-rated complications and comorbidities are massive, accounting for $370 billion in direct medical cost, over $1 trillion in indirect annual costs in the U.S.

我認為重要的是，它應該將減肥益處的討論從美學上轉移到肥胖人群的健康益處上。總體來看，有 236 種與肥胖相關的健康並發症。僅舉幾例，肥胖會使患 2 型糖尿病的風險增加 243%，冠心病的風險增加 69%，高血壓的風險增加 113%，血脂異常的風險增加 74%。在美國，肥胖引起的並發症和合併症的總體成本巨大，直接醫療成本高達 3700 億美元，間接年度成本超過 1 萬億美元。

People living with obesity or overweight drive 2.7 greater health care costs than normal-weight individuals. The global health stakeholders really need to be moved beyond the debate and really move to action on the AOM class. With tirzepatide's potential to provide over 20% weight loss, it should provide great value for payers. We have a comprehensive real-world evidence plan and clinical plan to demonstrate tirzepatide's value, including our MMO OUTCOMES trial.

肥胖或超重人群的醫療保健費用比正常體重人群高 2.7 倍。全球衛生利益相關者確實需要超越辯論，真正在 AOM 課程上採取行動。由於替澤帕肽有可能使體重減輕 20% 以上，因此它應該為付款人帶來巨大的價值。我們有一個全面的現實世界證據計劃和臨床計劃來證明替澤帕肽的價值，包括我們的 MMO OUTCOMES 試驗。

Based on the SELECT trial results, we can't wait to see the results of tirzepatide/MMO study. We do believe that additional weight loss will matter. This is a fantastic day for people living with obesity. Now do I think most payers will adopt AOMs overnight because of SELECT trial? I don't think so. I think, as I said earlier, those who are on the fence, this will push them over. But I think it is an important milestone in a long-term goal to get broad access for anti-obesity medications.

基於 SELECT 試驗結果，我們迫不及待地想看到替澤帕肽/MMO 研究的結果。我們確實相信額外的減肥很重要。對於肥胖症患者來說，這是美好的一天。現在我認為大多數付款人會因為 SELECT 試用而一夜之間採用 AOM 嗎？我不這麼認為。我認為，正如我之前所說，那些持觀望態度的人，這會將他們推倒。但我認為這是廣泛獲得抗肥胖藥物的長期目標的一個重要里程碑。

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

下一個問題來自美國銀行的傑夫·米查姆。

I know that we're a year into the [major launch], but I wanted to get a view of persistent rates. The question is, are you seeing drug holidays after weight loss troughs? And I wasn't sure if there were differences between diabetes and obesity indications at this point just with regard to duration of use.

我知道[主要發布]已經一年了，但我想了解一下持續的利率。問題是，你在減肥低谷後會看到藥物假期嗎？我不確定目前糖尿病和肥胖症的適應症在使用持續時間方面是否存在差異。

Thanks, Geoff. I'll go back to Mike for that question on persistence rates of Mounjaro.

謝謝，傑夫。我將回到 Mike 那裡詢問有關 Mounjaro 持久率的問題。

Okay. Geoff, thanks for your question. Right now, we only market Mounjaro for type 2 diabetes. So the only end-market real-world persistency rates that we have are for Mounjaro in type 2 diabetes patients. What we do know is that people living with type 2 diabetes have had good experiences with Mounjaro.

好的。傑夫，謝謝你的提問。目前，我們僅銷售用於 2 型糖尿病的 Mounjaro。因此，我們唯一掌握的終端市場現實世界持續率是 Mounjaro 在 2 型糖尿病患者中的療效。我們所知道的是，2 型糖尿病患者在使用 Mounjaro 方面獲得了良好的體驗。

In the first launch, like at the first phase of launch before we've made savings card and experienced supply spot outages, type 2 diabetes patients to Mounjaro did have better persistency than Trulicity, which is important because Trulicity historically has had the best compliance in the diabetes market. So we're confident in the experiences that people who use Mounjaro for type 2 diabetes have. And we're excited to see what that will be for people living with product weight management when and if we get approved by the FDA.

在首次推出時，就像在推出儲蓄卡之前的第一階段一樣，經歷了供應點中斷，Mounjaro 的 2 型糖尿病患者確實比 Trulicity 具有更好的持久性，這一點很重要，因為 Trulicity 歷來在糖尿病市場。因此，我們對使用 Mounjaro 治療 2 型糖尿病的患者的體驗充滿信心。我們很高興看到，如果我們獲得 FDA 的批准，這將為那些通過產品體重管理生活的人們帶來什麼。

The next question is coming from Tim Anderson from Wolfe Research.

下一個問題來自沃爾夫研究中心的蒂姆·安德森。

So just going back to SELECT, a commonly held view is that positive results benefits every company in the category. And that's our view as well. But of course, Novo will be able to make the claim for quite some time that they're the only drug to have a proven cardiovascular benefit. So could that actually give them a big commercial advantage in the marketplace on things like payer coverage that would actually be to Lilly's detriment?

回到 SELECT，一個普遍持有的觀點是，積極的結果有利於該類別中的每個公司。這也是我們的觀點。當然，Novo 將能夠在相當長的一段時間內聲稱它們是唯一被證明對心血管有益的藥物。那麼，這是否真的會給他們在市場上帶來巨大的商業優勢，比如支付者保險，而這實際上會對禮來公司造成損害？

Thanks, Tim. I'll go back to Mike for that question, a follow-up on SELECT.

謝謝，蒂姆。我將回到 Mike 那裡詢問這個問題，這是 SELECT 的後續問題。

No, it's a good question. I don't think that will be the case. What we've seen is payers opt into the class, not a particular drug. So I don't think that will give them a differential impact within payer access. I think commercially, typically, health care professionals when they see results like this, it really helps the class more than any one individual product.

不，這是一個好問題。我認為情況不會如此。我們看到的是付款人選擇加入該類別，而不是特定的藥物。因此，我認為這不會給他們在付款人訪問方面帶來不同的影響。我認為商業上，通常，醫療保健專業人士在看到這樣的結果時，對班級的幫助確實比任何一種單獨的產品都大。

The next question is coming from Kerry Holford from Berenberg.

下一個問題來自貝倫貝格的克里·霍爾福德。

On the guidance, please, on OpEx. So clearly, operating costs higher than at least, the market anticipated in Q2. And you are now guiding to spend more on SG&A R&D through this year. So I'm just interested to learn more about what has changed through this quarter to continue to raise that OpEx outlook versus your previous record. Can you elaborate on the key drivers of that, please?

關於運營支出的指導。顯然，第二季度的運營成本至少高於市場預期。您現在正在指導今年在 SG&A 研發上投入更多資金。因此，我只是有興趣了解更多有關本季度發生的變化，以繼續提高運營支出前景（與之前的記錄相比）。您能詳細說明一下其關鍵驅動因素嗎？

Thanks, Kerry, for the question. And yes, we'll go to Anat with that commentary on the OpEx guide and additional context.

謝謝克里提出的問題。是的，我們將前往 Anat，了解有關 OpEx 指南的評論和其他背景信息。

Thanks, Kerry, for the questions. So we have raised, you're right, both SG&A guidance as well as R&D. The SG&A increases are primarily as a result of continued investment in the upcoming launches we have yet this year. As we're seeing the opportunities, we're excited to divest efficiently behind these opportunities and make them a reality for patients and for Lilly.

謝謝克里提出的問題。所以我們提出了，你是對的，SG&A 指導以及研發。 SG&A 的增長主要是由於我們對今年即將推出的產品進行了持續投資。當我們看到這些機會時，我們很高興能夠有效地剝離這些機會，並使它們成為患者和禮來公司的現實。

On the R&D side, Dan provided a robust outline of the progress we've seen in our pipeline. And there are really, I would say, 3 to 4 key drivers of that increase. One is additional new studies that we've announced primarily in Phase III. And you mean the broadening of the investments we're making in our incretin portfolio, initiating multiple Phase III studies for both orforglipron and retatrutide and announcing new studies, coupled with continued advancement. We're seeing great success in our early-stage pipeline and we're investing behind that.

在研發方面，丹提供了我們在管道中所看到的進展的有力概述。我想說，這種增長確實有 3 到 4 個關鍵驅動因素。其中之一是我們主要在第三階段宣布的其他新研究。你的意思是擴大我們對腸促胰素產品組合的投資，啟動奧福格列隆和瑞他魯肽的多項 III 期研究，並宣布新的研究，以及持續的進展。我們在早期管道中看到了巨大的成功，並且我們正在對其進行投資。

We're also seeing continued success in our enrollment rates for currently for our Phase III program. So that's continued to enroll well. And then the 3 business development transactions, the inbound that we've announced, are now going to be incorporated in our second half R&D run rate. So all these combined are the drivers of the increase this year. So they represent really a tremendous opportunity for continued investments in a very successful pipeline.

我們還看到目前第三階段項目的入學率持續取得成功。因此，招生情況繼續良好。然後，我們宣布的 3 項業務開發交易，現在將納入我們下半年的研發運行率。因此，所有這些加起來就是今年增長的驅動力。因此，它們確實代表了對非常成功的管道進行持續投資的巨大機會。

The next question is coming from Chris Schott from JPMorgan.

下一個問題來自摩根大通的克里斯·肖特。

Can you just walk through expectations for Mounjaro volumes and ASP as you move through 3Q and 4Q just given the change in the patient assistance program on June 30 as well as the North Carolina facility coming online? I guess, specifically, I was just wondering, do the IQVIA scripts we're now seeing largely reflect the change to the patient assistant program? And then should we expect volumes from North Carolina to be a meaningful contributor to capacity this year? Or is that more 2024?

鑑於 6 月 30 日患者援助計劃的變化以及北卡羅來納州設施的上線，您能否簡單介紹一下第三季度和第四季度時對 Mounjaro 銷量和平均售價的預期？我想，具體來說，我只是想知道，我們現在看到的 IQVIA 腳本是否在很大程度上反映了患者助理程序的變化？那麼我們是否應該期望北卡羅來納州的產量對今年的產能做出有意義的貢獻？或者說是 2024 年？

Was close to multiple questions there, Chris. But let me hand over to Mike to provide expectations on Mounjaro volume and gross-to-net dynamics as we move in the second half, given the RTP news, and then also given the changes to the co-pay program at the end of June. Mike?

克里斯，那裡有很多問題。但是，鑑於 RTP 消息以及 6 月底自付費用計劃的變化，讓我請 Mike 提供對下半年 Mounjaro 銷量和毛淨動態的預期。麥克風？

Chris, thanks for those questions. Yes, we did make the change in the $25 savings, program did expire at the end of June 30. So anything that you see in IQVIA is post that change. And you'll see that volume of those individuals who were using an uncovered plan no longer in our trends. We were very happy with what we saw with Mounjaro-pay TRxes in the quarter as they grew nearly 60% in the quarter.

克里斯，謝謝你提出這些問題。是的，我們確實對 25 美元儲蓄進行了更改，該計劃確實於 6 月 30 月底到期。因此，您在 IQVIA 中看到的任何內容都是更改後的。您會發現使用無保障計劃的人數不再出現在我們的趨勢中。我們對本季度 Mounjaro-pay TRx 的表現感到非常滿意，因為它們在本季度增長了近 60%。

As we go forward, we'll -- our manufacturing team is working on bringing on new capacity at North Carolina and then a few more areas. And as that production comes on and ramps up, we will see some benefit from that supply. I mean, ultimately, that will help build inventories up and help eliminate any spot outage that we see.

隨著我們的前進，我們的製造團隊正在努力在北卡羅來納州以及其他幾個地區增加新的產能。隨著產量的增加和增加，我們將從供應中看到一些好處。我的意思是，最終這將有助於建立庫存並有助於消除我們看到的任何局部停電。

In the short term, because we're seeing really unprecedented demand, we do still expect to see tight supply and some spot outages on Mounjaro through the end of the year. But I think ultimately as that manufacturing capacity ramps up, we will be out of the spot outages that we see. But in the next couple of months and quarters, I think we'll still see tightened (inaudible).

短期內，由於我們看到了前所未有的需求，我們仍然預計到今年年底，Mounjaro 的供應將會緊張，並且會出現一些現貨供應中斷。但我認為，隨著製造能力的提高，我們最終將擺脫我們所看到的局部停電的情況。但在接下來的幾個月和幾個季度，我認為我們仍然會看到收緊（聽不清）。

The next question is coming from Terence Flynn from Morgan Stanley.

下一個問題來自摩根士丹利的特倫斯·弗林。

I was just wondering if you could provide any perspective on how you're thinking about the potential for a single brand, for Mounjaro, or a split brand ahead of the potential FDA action on the obesity indication?

我只是想知道，在 FDA 對肥胖適應症採取潛在行動之前，您是否可以提供任何關於您如何看待單一品牌、Mounjaro 或拆分品牌的潛力的觀點？

Thanks, Terence. Mike, I'll hand that over to you for commentary on single brand versus multiple brands for tirzepatide.

謝謝，特倫斯。邁克，我將把它交給你來評論單一品牌與多品牌的替西帕肽。

Yes. Thanks for the question. We're evaluating all alternatives, and we'll announce our decision at approval.

是的。謝謝你的提問。我們正在評估所有替代方案，並會在批准後宣布我們的決定。

The next question is coming from Colin Bristow from UBS.

下一個問題來自瑞銀集團 (UBS) 的科林·布里斯托 (Colin Bristow)。

Congrats on the quarter. I heard the sort of positive commentary regarding the commercial supply coming online RTP. And just as we think about '24, how likely is it or what do you foresee in terms of supply potentially capping the sales potential in '24? And is the decision to move forward with the vials and multi-dose pen in any way related to delays at the RTP side?

恭喜本季度。我聽到了關於在線 RTP 商業供應的積極評論。正如我們思考 24 年一樣，您預計供應方面的可能性有多大，或者您預計什麼可能會限制 24 年的銷售潛力？繼續推進小瓶和多劑量注射筆的決定是否與 RTP 方面的延誤有關？

Thanks, Colin. I'm going to hand to Anat to talk a little bit about the RTP commercial supply and supply dynamics in the near term.

謝謝，科林。我將請 Anat 談談近期的 RTP 商業供應和供應動態。

Colin, so let me first start with the end of your question on -- just to clarify RTP. So RTP is now live and producing for commercial purposes, and it's on line, in line with our expectations. So there are no delays. It's progressing as we had expected. I'm incredibly proud of the work that the manufacturing team have done to get us to this point.

Colin，讓我首先從你問題的結尾開始——只是為了澄清 RTP。因此，RTP 現在已投入使用並用於商業目的，並且已經上線，符合我們的預期。所以不會有任何延誤。事情的進展正如我們預期的那樣。我對製造團隊為實現這一目標所做的工作感到無比自豪。

As Mike alluded, there will be a gradual increase in available capacity coming out of that site. We've mentioned in the past, it's a large site with multiple lines. They'll come online gradually and provide more products into the marketplace.

正如邁克提到的，該站點的可用容量將逐漸增加。我們過去曾提到過，這是一個擁有多條線路的大型站點。他們將逐步上線並向市場提供更多產品。

As we think about 2024, I suggest we step back and look comprehensively at our manufacturing agenda and capacity plans. So RTP is one side. It's obviously of high interest just because of the proximal nature, and that's the first one that's launched out of the number of sites we have under construction.

當我們思考 2024 年時，我建議我們退後一步，全面審視我們的製造議程和產能計劃。所以RTP是一方面。顯然，由於其鄰近性，它引起了人們的高度興趣，而且這是我們在建的眾多站點中推出的第一個。

In parallel, we have been working and continue to work to expand capacity in existing sites. We're working with partners and CMOs to supplement capacity. And our strategy is, first and foremost, to have an internal build but then we supplement externally as needed. But we're also progressing with -- rapidly with our site in North -- the second site, North Carolina in Concord, which you recall we've announced last year. And that could potentially go live in terms of production in the second half of 2024, again, gradually. So we will see some relief of supply at the end of -- or towards the end of next year and then continue to grow from there.

與此同時，我們一直在努力擴大現有站點的產能，並將繼續努力。我們正在與合作夥伴和 CMO 合作來補充產能。我們的策略首先是內部建設，然後根據需要進行外部補充。但我們也在快速推進我們在北卡羅來納州的第二個站點，即位於康科德的北卡羅來納州，您還記得我們去年已經宣布了這一點。這可能會在 2024 年下半年逐步投入生產。因此，我們將在年底或明年底看到供應有所緩解，然後繼續增長。

And as you know, this is -- these are not the only 2 nodes of capacity. We're also adding outside of incretin and for incretin, API capacity in Ireland as well as 2 large sites in Indiana. So we're expanding capacity broadly to support both the incretin portfolio but then the broader Lilly portfolio, and managing a broad set of networks outside of Lilly. So a complex manufacturing set of nodes that we're working towards.

如您所知，這並不是僅有的 2 個容量節點。我們還在愛爾蘭增加了腸促胰島素以外的 API 產能以及印第安納州的 2 個大型工廠。因此，我們正在廣泛擴大產能，以支持腸促胰素產品組合，然後支持更廣泛的禮來公司產品組合，並管理禮來公司之外的廣泛網絡。因此，我們正在努力實現一組複雜的製造節點。

We'll comment on -- specifically on 2024 when we provide guidance in terms of what you should expect in revenue. But this is how you should think about the gradual increase in supply with both RTP, internal capacity elsewhere as well as CMOs. The additional presentation is meant to provide options for patients. And as we've said, we'll start launching outside the U.S. with these presentations will -- which should provide additional capacity as well. And as I stated earlier, the manufacturing facilities in line already exists within Lilly for, for example, the vial production. We have those facilities. We don't need to construct new ones. So that provides us with the option to start with these as early as the end of this year and then going into next year.

我們將特別針對 2024 年的收入發表評論，屆時我們將就您的收入預期提供指導。但這是您應該如何考慮 RTP、其他地方的內部產能以及 CMO 供應的逐漸增加。額外的介紹旨在為患者提供選擇。正如我們所說，我們將開始在美國境外推出這些演示文稿，這也應該提供額外的容量。正如我之前所說，禮來公司內部已經存在用於小瓶生產的生產設施。我們有這些設施。我們不需要建造新的。因此，這為我們提供了最早在今年年底開始，然後到明年的選擇。

The next question is coming from Steve Scala from Cowen.

下一個問題來自 Cowen 的 Steve Scala。

How should we think about the MACE reduction powering in SURMOUNT MMO now that we have the SELECT results? SURMOUNT MMO likely won't be as robust given the population studied, but would Lilly consider a win something half of SELECT's 20% MACE reduction? Or would that be viewed as disappointing?

既然我們有了 SELECT 結果，我們應該如何考慮 SURMOUNT MMO 中 MACE 的減少？考慮到所研究的人群，SURMOUNT MMO 可能不會那麼強大，但禮來公司是否會認為勝利相當於 SELECT 20% MACE 減少的一半？或者這會被視為令人失望嗎？

Thanks, Steve. I'll hand over to Dan for that.

謝謝，史蒂夫。我會把這件事交給丹。

Yes. Thanks, Steve, for your provocative question here. Actually, of course, we expect tirzepatide to show a very important benefit, I think, on the MMO study. There are several important differences as you're alluding to. I think for the most part, though, they run in the opposite direction as you're suggesting, which would indicate a potential for an even larger effect size for SURMOUNT MMO.

是的。史蒂夫，謝謝你提出的挑釁性問題。事實上，我認為，當然，我們期望替西帕肽在 MMO 研究中顯示出非常重要的益處。正如您所提到的，有幾個重要的區別。不過，我認為在大多數情況下，它們的運行方向與您所建議的相反，這表明 SURMOUNT MMO 的效應規模可能更大。

The most important difference is the drug itself. Remember that tirzepatide is a GLP/GIP coagonist, and GIP has some very significant benefits on weight loss and metabolic health overall. We've seen that in a number of different trials and confirm that with some interesting experiments on GIP monotherapy as well.

最重要的區別是藥物本身。請記住，替西帕肽是 GLP/GIP 共激動劑，GIP 對減肥和整體代謝健康有一些非常顯著的益處。我們在許多不同的試驗中看到了這一點，並通過一些關於 GIP 單一療法的有趣實驗證實了這一點。

So given the properties of this drug, given the level of weight loss we've seen in previous trials, given the important effects on blood pressure, on lipid profiles and on other biomarkers that indicate lower cardiovascular risk, we should be very confident in the large effect size coming out of the MMO study.

因此，考慮到這種藥物的特性，考慮到我們在之前的試驗中看到的體重減輕水平，考慮到它對血壓、血脂和其他表明心血管風險較低的生物標誌物的重要影響，我們應該非常有信心MMO 研究得出的巨大效應量。

There are some differences in the population. Our study includes both primary and secondary cardiovascular risk population. We also have a different primary end point, although, of course, we have the [3-point] MACE as a secondary end point. Our primary includes 2 other events related to cardiovascular risk.

人群存在一些差異。我們的研究包括主要和次要心血管危險人群。我們還有一個不同的主要終點，當然，我們有 [3 點] MACE 作為次要終點。我們的主要事件包括另外 2 個與心血管風險相關的事件。

Other than that, I would say that many of the patient characteristics are going to be quite similar. Our study is obviously much earlier. And as an event-driven study, it's going to take some time to read out. I think you were also asking about what would be considered a victory here, and I think we'll just sort of wait and see the data and understand it as it comes but no reason to expect anything less than what we're seeing today.

除此之外，我想說，許多患者的特徵將非常相似。我們的研究顯然要早得多。作為一項事件驅動的研究，需要一些時間來讀出。我想你也在問什麼才算是一場胜利，我想我們只是等待，看看數據並理解它的到來，但沒有理由期待任何比我們今天看到的更好的事情。

Next question is coming from Umer Raffat from Evercore.

下一個問題來自 Evercore 的 Umer Raffat。

I wanted to zoom in on orforglipron and specifically on the case of liver enzymes, above 5x and a case above 10x as well as the treatment-emergent hepatobiliary disorders. I know the slides mentioned safety was similar to other incretins. And my question is, is your opinion on liver safety driven by the fact that these liver enzymes self-resolved? Or is it some preclinical data like the GSS ad hoc formation, et cetera?

我想重點關注 orforglipron，特別是肝酶超過 5 倍的病例和超過 10 倍的病例，以及治療中出現的肝膽疾病。我知道幻燈片提到的安全性與其他腸促胰島素類似。我的問題是，您對肝臟安全性的看法是否是由這些肝酶自行解決的事實驅動的？或者是一些臨床前數據，例如 GSS 特別形成等？

Thanks, Umer, for the question. I'll hand over to Dan for that question on orforglipron liver dynamics.

謝謝烏默提出的問題。我將把有關 orforglipron 肝臟動力學的問題交給 Dan。

Yes, thanks for the question. Of course, there's been more attention on liver safety for orforglipron following the competitor announcement from Pfizer on 1 of their 2 oral GLP-1s. So we don't see any read-through from that. But of course, we've looked very carefully at liver safety.

是的，謝謝你的提問。當然，在輝瑞公司宣布其 2 種口服 GLP-1 中的 1 種為競爭對手後，orforglipron 的肝臟安全性受到了更多關注。所以我們沒有看到任何通讀的內容。當然，我們非常仔細地研究了肝臟安全性。

Maybe just starting at a high level, if you look at the supplementary data from the journal publication or you can see in the obese population that in terms of group averages, there's actually an improvement on liver enzymes with treatment of orforglipron. That's not surprising. We know that disease obesity is characterized in many patients by excess liver fat, which can cause inflammation and liver abnormalities. And when you reverse that, you see an improvement in liver function.

也許只是從高水平開始，如果您查看期刊出版物中的補充數據，或者您可以在肥胖人群中看到，就群體平均值而言，使用奧格列隆治療後，肝酶實際上有所改善。這並不奇怪。我們知道，許多患者的疾病性肥胖的特點是肝臟脂肪過多，這會導致炎症和肝臟異常。當你扭轉這種情況時，你會看到肝功能得到改善。

Of course, when people come off the drug, they could get fat in their liver again and liver enzymes could go up. What we saw in this trial were a couple of patients scattered across arms, including placebo with excursions and liver enzymes, as you point out to -- I think there was one patient, with a bit of a higher excursion in liver enzymes on orforglipron that returned to normal levels while maintaining on therapy. That's generally not a pattern that we see in drugs that cause liver injury. But surely in Phase III, we'll keep an eye open for all possible safety consequences.

當然，當人們停藥後，他們的肝臟可能會再次出現脂肪，肝酶可能會上升。我們在這項試驗中看到的是，幾名患者分散在手臂上，包括安慰劑和肝酶，正如您所指出的，我認為有一名患者在使用 orforglipron 時，肝酶的偏移較高，在維持治療的同時恢復到正常水平。這通常不是我們在導致肝損傷的藥物中看到的模式。但在第三階段，我們肯定會密切關注所有可能的安全後果。

I think I frequently caution investors on all of our molecules that Phase III is really the place where you can get surprised by any new safety findings. So we'll be watching liver safety closely, but not with any particularly heightened concern versus other adverse events that we'll also be watching carefully. This is a new molecule. This is the first time that we're exposing large, large numbers of patients to it for many years -- or many, many months, I should say, and we'll be monitoring safety carefully.

我想我經常提醒我們所有分子的投資者，第三階段確實是任何新的安全發現都會讓你感到驚訝的地方。因此，我們將密切關注肝臟安全，但不會特別高度關注我們也會密切關注的其他不良事件。這是一個新分子。這是我們多年來第一次讓大量患者接觸它，或者我應該說很多很多個月，我們將仔細監控安全性。

The next question is coming from David Risinger from Leerink Partners.

下一個問題來自 Leerink Partners 的 David Risinger。

So my question is for Dan, please. How are you thinking about whether future orthogonal mechanism weight-loss drugs can deliver the cardiovascular outcomes of incretins even if they match weight loss on a pound-for-pound basis?

我的問題是問丹的。您如何看待未來的正交機制減肥藥是否可以提供腸促胰島素的心血管結局，即使它們與體重減輕相匹配？

Dan?

擔？

Yes. Thanks, David. It's a very good question, of course, particularly today. We think we understand how the biomarkers from incretin therapy translate into cardiovascular benefits. Some of those biomarkers should be translatable to other mechanisms. But depending on how orthogonal those other mechanisms are, there could still be some uncertainty.

是的。謝謝，大衛。當然，這是一個非常好的問題，尤其是在今天。我們認為我們了解腸促胰島素治療的生物標誌物如何轉化為心血管益處。其中一些生物標誌物應該可以轉化為其他機制。但根據其他機制的正交程度，仍然可能存在一些不確定性。

One, I think, important understanding, though, is that obesity itself, including, I think, particularly where the fat is deposited in the body, so for example, virtual fat, particularly, is -- contributes to adverse health outcomes, including adverse cardiovascular outcomes. And therefore, reversing that should provide cardiovascular benefits across mechanisms. But obviously, when we get to orthogonal mechanisms, each one will need its own data to demonstrate that. Recently, our focus has been on mechanisms that could stack on top of incretin therapy to give additional benefits in which case there could be a good read-through from the incretin trough. Thanks, David.

不過，我認為，重要的一點是，肥胖本身，尤其是脂肪沉積在體內的地方，例如虛擬脂肪，尤其會導致不良的健康結果，包括不良的健康後果。心血管結局。因此，扭轉這種情況應該可以通過多種機制提供心血管益處。但顯然，當我們談到正交機制時，每個機制都需要自己的數據來證明這一點。最近，我們的重點是可以疊加腸促胰島素治療的機制，以提供額外的益處，在這種情況下，可以從腸促胰島素槽進行良好的讀取。謝謝，大衛。

The next question is coming from Chris Shibutani from Goldman Sachs.

下一個問題來自高盛的 Chris Shibutani。

Trulicity and Mounjaro, can you talk a little bit about the dynamics there? In particular, are you seeing switching? Just trying to get a sense for how you're seeing the supply and then the revenue dynamic.

Trulicity 和 Mounjaro，您能談談那裡的動態嗎？特別是，您是否看到了轉變？只是想了解一下您如何看待供應和收入動態。

Thanks, Chris. I'll hand over to Mike to talk about Trulicity and Mounjaro, and any switching dynamics or observations we have. Mike?

謝謝，克里斯。我將交給 Mike 來談談 Trulicity 和 Mounjaro，以及我們所擁有的任何切換動態或觀察結果。麥克風？

Yes. No, good question. Obviously, it's something we've taken a look at since the launch. Really haven't seen any trend breaks in what we've seen and how much of Trulicity is being converted over to Mounjaro. We've seen about 13% to 14% of patients coming on to Mounjaro come on from Trulicity. So really no changes from what we've seen at launch. Overall, our goal is to grow the entire Lilly incretin franchise, and we did that well in Q2 by growing revenue by over 58%. So we're pleased where we're at with the -- with our Lilly incretin pipeline, our portfolio, and are excited to grow it further in quarters to come.

是的。不，好問題。顯然，自推出以來我們就一直在關注這一點。我們確實沒有看到任何趨勢突破，也沒有看到 Trulicity 的多少正在轉換為 Mounjaro。我們發現大約 13% 至 14% 接受 Mounjaro 治療的患者來自 Trulicity。因此，與我們在發佈時看到的情況相比，確實沒有任何變化。總體而言，我們的目標是發展整個禮來腸促胰素系列產品，我們在第二季度做得很好，收入增長了 58% 以上。因此，我們對禮來腸促胰素產品線和產品組合的現狀感到滿意，並很高興在未來幾個季度進一步發展它。

The next question is coming from Mohit Bansal from Wells Fargo.

下一個問題來自富國銀行的 Mohit Bansal。

Congrats. I have a comment and a question, a comment from an associate that Lilly needs to have 2 calls, one for Mounjaro and one for everything else. So my question is -- the question is basically, how should we think about long-term supply now that the success of CV trial would likely spur more demand here? I know in the past, you talked about double of Trulicity eventually, but how should we think about the eventual supply of Mounjaro and Trulicity combined?

恭喜。我有一條評論和一個問題，一位同事的評論說，Lilly 需要打兩次電話，一次打給 Mounjaro，一次打給其他一切。所以我的問題是——問題基本上是，既然CV試驗的成功可能會刺激這裡的更多需求，我們應該如何考慮長期供應？我知道過去您談到了 Trulicity 最終的雙倍，但我們應該如何考慮 Mounjaro 和 Trulicity 的最終供應量之和？

Thanks, Mohit. We'll take your comment under advisement. It's a fair point. To your question on long-term supply, I'll maybe hand back to Anat to talk a little bit more about manufacturing dynamics and plans.

謝謝，莫希特。我們會考慮您的意見。這是一個公平的觀點。對於你關於長期供應的問題，我可能會回到阿納特來更多地談論製造動態和計劃。

Yes. So Mohit, I would echo a few of the things I said earlier. I outlined the expansion we are going to be seeing in our manufacturing footprint across our portfolio. So it's not just to support the incretin portfolio. But certainly with the RTP site in North Carolina and Concord, they're both for -- to support our incretin portfolio. They're both large sites. We did not provide the specific quantities, but we said that once RTP comes online by the end of the year, we expect to double capacity from where we were last year. So just use that kind of as a reference point.

是的。因此，莫希特，我會重複我之前所說的一些事情。我概述了我們將在整個產品組合中看到的製造足蹟的擴張。因此，這不僅僅是為了支持腸促胰素產品組合。但可以肯定的是，在北卡羅來納州和康科德的 RTP 站點，它們都是為了支持我們的腸促胰島素產品組合。它們都是大型網站。我們沒有提供具體數量，但我們表示，一旦 RTP 在今年年底上線，我們預計產能將比去年翻一番。因此，只需使用這種作為參考點即可。

Trulicity and Mounjaro as you know are -- both utilize the same auto-injector. So they run on the same platform. And these lines are interchangeable, which allows us to manage production plans across our sites based on where we want or need to produce a product or market demand, et cetera. So we're going to be expanding our internal footprint to support the incretin portfolio as well as continue to leverage external partners to supplement that capacity.

如您所知，Trulicity 和 Mounjaro 都使用相同的自動注射器。所以它們運行在同一個平台上。這些生產線是可以互換的，這使我們能夠根據我們想要或需要生產產品的地點或市場需求等來管理我們各個站點的生產計劃。因此，我們將擴大我們的內部足跡以支持腸促胰素產品組合，並繼續利用外部合作夥伴來補充這一能力。

The next question is coming from Evan Seigerman from BMO.

下一個問題來自 BMO 的 Evan Seigerman。

I'm going to ask one on donanemab to shake it up a little bit. So in submitting for donanemab full approval, are there any nuances that you needed to discuss with the agency following the CRL earlier this year? Or does FDA have everything that they need based on the data that we saw last month?

我要請多納奈馬布（donanemab）的一位人士來稍微改變一下。那麼，在提交 donanemab 獲得全面批准時，您是否需要在今年早些時候的 CRL 之後與該機構討論任何細微差別？或者根據我們上個月看到的數據，FDA 是否擁有他們所需的一切？

So much for the question on donanemab. And just to refresh Evan's memory, we have submitted accelerated approval submission, which was designated as a priority review. We did receive a CRL just based really on wanting more exposure. So it's a pretty simple request.

關於多納奈單抗的問題就這麼多。為了讓埃文重溫記憶，我們提交了加速審批提交，該提交被指定為優先審查。我們確實收到了 CRL，只是因為我們想要更多的曝光。所以這是一個非常簡單的請求。

Our resubmission with TRAILBLAZER-ALZ 2, the Phase III study, which certainly fulfilled any expectations on the CRL. And those good news, I think going through the accelerated approval, the FDA had the chance to review all of the aspects of the submission, preclinical manufacturing and others. So I would say we feel pretty confident at this point about the quality of our submission. And they've accepted that. They're reviewing it for traditional approval. So as we've said, we expect action by the end of the year.

我們重新提交了 TRAILBLAZER-ALZ 2（III 期研究），這無疑滿足了 CRL 的任何期望。這些好消息，我認為通過加速批准，FDA 有機會審查提交、臨床前製造和其他方面的所有方面。所以我想說，我們目前對提交的質量非常有信心。他們已經接受了這一點。他們正在審查它以獲得傳統批准。正如我們所說，我們預計在今年年底前採取行動。

The next question is coming from Robyn Karnauskas from Truist Securities.

下一個問題來自 Truist Securities 的 Robyn Karnauskas。

I guess I have a big-picture question. So you're in payer discussions right now ahead of approval for weight loss from Mounjaro. For those payers that are not willing to cover, not on the fence, what do they need to see as you expect the cadence of supply versus access to shift in 5 years? Can you give us a sense of what that looks like and what they really need to see?

我想我有一個大局問題。因此，在 Mounjaro 批准減肥之前，您現在正在與付款人進行討論。對於那些不願意支付、不持觀望態度的付款人，當您預計供應與獲取的節奏在 5 年內發生變化時，他們需要看到什麼？您能否讓我們了解一下這是什麼樣子以及他們真正需要看到什麼？

Thanks, Robyn. I'll hand over to Mike. It sounds like the question is more around kind of payer discussions longer term and for those that are more maybe reticent, what might eventually move some of these payers. Mike, do you want to comment?

謝謝，羅賓。我將把工作交給邁克。聽起來問題更多的是圍繞付款人的長期討論，對於那些可能比較沉默寡言的人來說，什麼最終可能會感動其中一些付款人。邁克，你想發表評論嗎？

Yes. I think there's a couple of dynamics that will play out. I mean, first of all, we need to build a long-term clinical and real-world evidence to support payers' decisions, and we're doing that. We're spending literally billions of dollars in clinical evidence to show what tirzepatide and our pipeline can offer patients who have obesity and payers with regards to medical cost savings. We're confident in our modeling that payers will see medical cost offset with tirzepatide. And so I think that will be an important piece of it.

是的。我認為將會產生一些動力。我的意思是，首先，我們需要建立長期的臨床和現實證據來支持付款人的決定，我們正在這樣做。我們花費了數十億美元的臨床證據來展示替西帕肽和我們的產品線可以為肥胖患者和付款人節省醫療成本。我們對我們的模型充滿信心，付款人將看到替澤帕肽抵消醫療費用。所以我認為這將是其中的重要組成部分。

I think the other dynamic is a lot of times, we focus on the clinical story. But there is things beyond the economic analysis that I think will play a role. If you go and really discuss with people who live with obesity, improving their health is a top personal goal. Sadly, when we look at the data, 82% people live with obesity experience physical functioning reductions, while 77% experience reduced mental, emotional well-being.

我認為另一個動態是很多時候，我們關注臨床故事。但我認為除了經濟分析之外，還有一些事情也會發揮作用。如果您去與肥胖患者進行真正的討論，那麼改善他們的健康就是首要的個人目標。可悲的是，當我們查看數據時，82% 的肥胖者經歷了身體機能下降，而 77% 的人經歷了精神和情感健康下降。

Patients using tirzepatide showed significant improvements in physical, mental and emotional well-being in the SURMOUNT-1 trial. And it's clear from the patient testimonies that we had in our SURMOUNT clinical trials that tirzepatide can meaningfully improve the lives of people with obesity.

SURMOUNT-1 試驗中，使用替澤帕肽的患者在身體、心理和情緒健康方面表現出顯著改善。從 SURMOUNT 臨床試驗中的患者證詞可以清楚地看出，替西帕肽可以有效改善肥胖症患者的生活。

The massive interest that we see in obesity medications is really driven by the fundamental desire for people living with obesity to improve their health. People live with obesity should have a loud and powerful voice in this debate. And I think that's going to be a big component of payer decisions, whether that be an employer or be state or federal government. And so I think what you're going to see is over time, you're going to see data like the SELECT data, data like MMO or other clinical trials, continuing to build the case on economic side for these. While you're going to see the voice of people living with obesity who really want a better life, more hope for the future, who will be demanding access for these agents. And I think both over time, we'll continue to build access across the U.S. as well as globally.

我們看到人們對肥胖藥物的巨大興趣實際上是由肥胖症患者改善健康的基本願望所驅動的。肥胖患者應該在這場辯論中發出響亮而有力的聲音。我認為這將成為付款人決策的重要組成部分，無論是雇主還是州政府或聯邦政府。所以我認為隨著時間的推移，你會看到像 SELECT 數據、MMO 或其他臨床試驗這樣的數據，繼續為這些數據建立經濟方面的案例。雖然你會看到肥胖症患者的聲音，他們確實想要更好的生活，對未來有更多的希望，但他們會要求獲得這些藥物。我認為隨著時間的推移，我們將繼續在美國乃至全球範圍內建立訪問權限。

The next question is coming from Andrew Baum from Citi.

下一個問題來自花旗銀行的安德魯·鮑姆 (Andrew Baum)。

A non-Mounjaro and non-donanemab question coming up. We estimate there's about $2 billion of Dupixent in the U.S. from adults with atopic dermatitis. When you are thinking about the launch of lebrikizumab, given the relatively little clinical differentiation, and therefore, the need to displace the Dupixent, could you just comment on how you're thinking about the launch? I'm assuming similar to Wegovy or (inaudible) to some similar to Mounjaro or (inaudible), the obvious thing would be to launch a very, very large bridge program in order to secure formulary access, tapping into that high-deductible patient population. Just interested in your thoughts here, please.

出現了一個非 Mounjaro 和非 donanemab 的問題。我們估計，在美國，患有特應性皮炎的成人使用 Dupixent 獲得的銷售額約為 20 億美元。當您考慮推出 lebrikizumab 時，考慮到臨床差異相對較小，因此需要取代 Dupixent，您能否簡單評論一下您是如何考慮推出這款藥物的？我假設類似於 Wegovy 或（聽不清）類似於 Mounjaro 或（聽不清），顯而易見的事情是啟動一個非常非常大的橋樑計劃，以確保獲得處方藥，利用高免賠額患者群體。只是對您的想法感興趣。

Thanks, Andrew, for diversifying the question set. I'll hand over to Patrik, President of Lilly Immunology, to weigh in on lebrikizumab and how we're thinking about positioning. Patrik?

感謝安德魯使問題集多樣化。我將請禮來免疫學總裁帕特里克 (Patrik) 來權衡 lebrikizumab 以及我們如何考慮定位。帕特里克？

Thank you very much for the question on lebrikizumab. Now based upon the data we have seen, we realized it's not a head-to-head, but we're extremely encouraged by the maintenance data, having more than 80% of patients achieving skin clearance at week 16 and maintaining it at week 52. We really believe that we are positioned to launch a first-line biologic that actually has less frequent dosing than Dupixent. So that's a big differentiator and targeting the most relevant cytokine for atopic dermatitis, being IL-13 with a slow rate and high potency.

非常感謝您關於 lebrikizumab 的問題。現在，根據我們看到的數據，我們意識到這不是正面交鋒，但我們對維護數據感到非常鼓舞，超過 80% 的患者在第 16 週實現皮膚清除，並在第 52 周維持該狀態. 我們確實相信，我們有能力推出一款實際上比Dupixent 給藥頻率更低的一線生物製劑。因此，這是一個很大的區別，它針對的是與特應性皮炎最相關的細胞因子，即 IL-13，其作用速度慢且效力高。

From an access perspective, we see we have atopic dermatitis market growing significantly. And we know that payers are looking forward to options here. So we are believing but PBMs are willing to enter into discussions to enable a rapid access of lebrikizumab. And of course, here, we can capitalize on the strong footprint we have in dermatology and the portfolio we currently have in immunology. And our strategy will entirely focus on value and the differentiation with our medicine and what it brings to the marketplace for atopic dermatitis.

從准入角度來看，我們看到特應性皮炎市場正在顯著增長。我們知道付款人期待在這裡的選擇。因此，我們相信，但 PBM 願意參與討論，以實現 lebrikizumab 的快速獲取。當然，在這裡，我們可以利用我們在皮膚病學方面的強大足跡以及我們目前在免疫學方面的產品組合。我們的戰略將完全專注於我們的藥物的價值和差異化以及它為特應性皮炎市場帶來的影響。

The next question is coming from Carter Gould from Barclays.

下一個問題來自巴克萊銀行的卡特·古爾德。

I appreciate all the color on the manufacturing side. At the same time, Anat, a lot of those sites you talked about, those were sort of in your plans to start the year. So I guess my question is, as we think about sort of the derisking of orforglipron, the move to Phase III, has that in any way changed your sort of expected build-out for your longer-term manufacturing needs and really on the peptide side of the incretin side?

我欣賞製造方面的所有顏色。與此同時，阿納特，你談到的很多網站，都在你今年開始的計劃中。所以我想我的問題是，當我們考慮消除 orforglipron 的風險時，轉向第三階段，這是否以任何方式改變了您對長期製造需求的預期建設，以及真正在肽方面的預期建設腸促胰島素一側？

Thanks, Carter. Great question. I think Dave wants to maybe jump in on this one.

謝謝，卡特。很好的問題。我想戴夫也許想參與其中。

Yes. Sure. I'll jump in. I mean, just as we think about this over the long term, first of all, versus where we started the year, there is one change we're talking about today, which are these new presentations that we'll be launching beginning even this year into next year. It's important for people to know that the constraint we experience now is in the parenteral auto-injector space.

是的。當然。我會插話。我的意思是，正如我們從長遠角度思考這個問題一樣，首先，與我們今年年初的情況相比，我們今天討論的有一個變化，這就是我們的這些新演示文稿甚至從今年到明年都會推出。讓人們知道我們現在遇到的限制是在註射自動注射器領域，這一點很重要。

So to the degree we move outside of that, using our multi-dose pen that's currently developed for insulin and we're redeveloping for tirzepatide or certainly the vial, which is quite accessible and high-volume systems available, we'll be able to make more than we had planned previously, just to be clear. That's on top of sort of an on-schedule expansion at RTP in the other North Carolina site as well as other internal nodes of capacity. So I think that's good news for Mounjaro.

因此，就我們擺脫這一點而言，使用目前為胰島素開發的多劑量筆，我們正在重新開發替澤帕肽，或者當然是小瓶，這是相當容易獲得的，並且可以使用大容量系統，我們將能夠需要澄清的是，我們的收入超出了我們之前的計劃。這是在北卡羅來納州其他站點的 RTP 以及其他內部節點容量按計劃進行擴張的基礎上進行的。所以我認為這對 Mounjaro 來說是個好消息。

That all said, for the prior questions here, will that be enough to meet demand? I'm not so sure. So while the volume is moving up into the right, we need more. And does like today's news, will only expand the opportunity. So you're right to point out that other molecules, in orforglipron in particular, could play a big role in meeting global demand for obesity treatment and all the related complications because it's a completely different technology in that it's using oral solid, and there's quite a bit of capacity around the globe for that.

話雖如此，對於前面的問題，這足以滿足需求嗎？我不確定。因此，當音量向右移動時，我們需要更多。確實像今天的新聞一樣，只會擴大機會。因此，您正確地指出，其他分子，特別是Orforglipron，可以在滿足全球肥胖治療和所有相關並發症的需求方面發揮重要作用，因為它是一種完全不同的技術，因為它使用口服固體，並且有相當多的全球範圍內有一定的能力。

Orforglipron is a complicated molecule to make. It's got many steps. But it puts us in using a different set of assets and processes than the current ones we're using. So that's an important program, particularly for global access and availability over the long term. Just to remember as well, 2 years ago, we were probably treating 10 million people globally with incretins. And the WHO is estimating there'll be 1 billion people with obesity and related conditions by 2050, I believe. So a long way away from getting all the way to that. We need things like orforglipron to work for us to meet the needs of all the patients in the world.

Orforglipron 是一種製造起來很複雜的分子。它有很多步驟。但這使我們使用了與我們當前使用的不同的資產和流程。因此，這是一個重要的計劃，特別是對於長期的全球訪問和可用性而言。請記住，兩年前，我們可能正在用腸促胰島素治療全球 1000 萬人。我相信，世界衛生組織估計，到 2050 年，將有 10 億人患有肥胖症和相關疾病。距離實現這一目標還有很長的路要走。我們需要像 orforglipron 這樣的東西來為我們服務，以滿足世界上所有患者的需求。

The next question is coming from Trung Huynh from Credit Suisse.

下一個問題來自瑞士信貸銀行的 Trung Huynh。

Just one on IRA. So one of the components that's been implemented in the part -- is the Part D redesign that starts impacting in '24, and then there's going to be some more meaningful changes in '25. On our calculations, we think it should benefit products under $25,000 a year, like your GLP-1 portfolio, but a negative for drugs priced above $25,000 a year. So given the mix of products you have in your portfolio at various different price points, directionally, how do you see that impacting earnings in the next few years?

IRA 上只有一個。因此，該部分中實施的組件之一是 D 部分的重新設計，該部分從 24 年開始產生影響，然後在 25 年將出現一些更有意義的變化。根據我們的計算，我們認為它應該有利於每年 25,000 美元以下的產品，例如您的 GLP-1 產品組合，但對每年定價高於 25,000 美元的藥物不利。因此，考慮到您的投資組合中各種不同價位的產品組合，您認為這對未來幾年的收益有何影響？

Thanks, Trung. I'm going to hand to Anat for that comment -- for that response on the IRA and potential impacts.

謝謝，特朗。我將請阿納特（Anat）發表評論——對愛爾蘭共和軍（IRA）及其潛在影響的回應。

Yes. So if we -- I think you were referring to the Part D redesign associated with removing the coverage gap, but I'll also mention the negotiation. I wouldn't necessarily look at what the dollar amount is. But rather, you're right, there are going to be varying degrees of impact on products based on how quickly they move through the catastrophic phase.

是的。因此，如果我們 - 我認為您指的是與消除覆蓋範圍差距相關的 D 部分重新設計，但我也會提到談判。我不一定會看美元金額是多少。但相反，你是對的，根據產品度過災難階段的速度，會對產品產生不同程度的影響。

So just to give an example from Lilly. If you're thinking about an oncology product where patients get to the catastrophic phase very quickly, there is probably an additional cost associated with that for us moving from the previous 70% coverage gap to the 10% participation in the initial phase and then 20% in the catastrophic phase. For other indications, it might be the opposite. So there is a mix there. But then important to think about the fact that given that patients are now going to have a limit of out-of-pocket when they get to the pharmacy counter, hopefully, that should improve adherence and compliance to medications, which should drive, obviously, better health outcomes for these patients, but also as we're thinking about medication kind of adherence. So there's going to be some pushes and pulls of that part of the IRA.

舉一個莉莉公司的例子。如果您正在考慮一種腫瘤產品，其中患者很快就會進入災難性階段，那麼對於我們來說，從之前的70% 覆蓋差距轉變為初始階段的10% 參與率，然後是20% 可能會產生額外的成本。 % 處於災難階段。對於其他跡象，情況可能相反。所以那裡有一種混合。但重要的是要考慮這樣一個事實，鑑於患者現在到達藥房櫃檯時自付費用受到限制，希望這應該會提高藥物的依從性和依從性，這顯然會推動，這些患者的健康結果會更好，而且我們正在考慮藥物的依從性。因此，愛爾蘭共和軍的這一部分將會受到一些推動和拉動。

The more significant one that I would refer to is the so-called negotiation that we have as part of that, that's going to come later in 2026 and 2028 with the first cohort of products to be announced this year. I think that could have quite a meaningful impact on the drugs that are going to be negotiated in terms of the price discounts that the government is going to arrive at as part of that process.

我要提到的更重要的一個是我們作為其中一部分進行的所謂談判，該談判將於 2026 年晚些時候和 2028 年進行，第一批產品將於今年發布。我認為這可能會對藥物產生相當有意義的影響，這些藥物將在政府在此過程中達成的價格折扣方面進行談判。

The last question is a follow-up from Kerry Holford from Berenberg.

最後一個問題是來自 Berenberg 的 Kerry Holford 的後續提問。

Just a quick one on Verzenio. Just interested to see whether you can tender from a proportion of those drug sales now are represented by use in the early breast cancer setting. And given we've now seen the Kisqali NATALEE data at ASCO, just interested to hear how you're thinking about competition coming into that space?

簡單介紹一下 Verzenio。只是想知道您是否可以從目前用於早期乳腺癌治療的藥物銷售中的一部分中進行投標。鑑於我們現在已經在 ASCO 上看到了 Kisqali NATALEE 的數據，只是想听聽您如何看待進入該領域的競爭？

Thanks, Kerry. All right, I'm going to hand over to Jake for that last question on Verzenio and the proportion of sales in early breast versus metastatic and maybe some commentary on NATALEE. Jake?

謝謝，凱瑞。好吧，我將把關於 Verzenio 的最後一個問題以及早期乳腺癌與轉移性乳腺癌的銷售比例以及可能對 NATALEE 的一些評論交給 Jake。傑克？

Yes. Thanks for the question. So I'll answer the proportion of sales really on new patients or NBRx. TRx is sort of a lagging indicator, of course, that takes into account iterations of therapy. But what we're seeing on the NBRx side is about, call it, between 30% and 45% of prescriptions are in early breast cancer versus metastatic. And obviously, that number bounces around sort of week-to-week, month-to-month. So that's more or less in line with what we expected. So that's what's happening there.

是的。謝謝你的提問。因此，我將回答新患者或 NBRx 的實際銷售比例。當然，TRx 是一種滯後指標，它考慮了治療的迭代。但我們在 NBRx 方面看到的是，30% 到 45% 的處方針對的是早期乳腺癌，而不是轉移性乳腺癌。顯然，這個數字每週、每月都在波動。所以這或多或少符合我們的預期。這就是那裡發生的事情。

On the competitive dynamics in the adjuvant setting, now that we've seen the NATALEE data from Kisqali at ASCO, which by the way, were not really surprising to us, I think when you take a step back, and this is sort of both our opinion as well as what we've heard from thought leaders, we just really don't see what the Kisqali 3-year regimen is giving to patients to justify the additional year of therapy relative to the 2-year regimen that we've offered patients with Verzenio. Obviously, cross-trial comparisons notwithstanding, if anything, you see a marginally larger effect size with the 2-year Verzenio regimen in high-risk patients, obviously, the NATALEE study studied a larger population. The node-negative patients are at lower risk and frankly, not part of our indication. We didn't study those patients. I think to the extent that folks want to use Kisqali there, that's not really our business. Maybe it could be beneficial for those patients, I can't really say.

關於佐劑環境中的競爭動態，現在我們已經看到了 ASCO 的 Kisqali 的 NATALEE 數據，順便說一句，這對我們來說並不令人驚訝，我認為當你退一步時，這兩者都是根據我們的觀點以及我們從思想領袖那裡聽到的意見，我們只是真的不明白Kisqali 3 年方案給患者帶來了什麼，以證明相對於我們已經採用的2 年方案額外一年的治療是合理的為患者提供Verzenio。顯然，儘管進行了交叉試驗比較，但如果有的話，您會發現 2 年 Verzenio 方案在高危患者中的效果稍大，顯然，NATALEE 研究研究了更大的人群。淋巴結陰性患者的風險較低，坦率地說，這不屬於我們的適應症。我們沒有研究那些患者。我認為人們想在那裡使用 Kisqali，那不是我們的事。也許這對那些患者有益，我真的不能說。

I think the other thing, and Dan mentioned this in the prepared remarks, is that there's been a lot of talk in the past, of course, about the differences in the tolerability of these two agents. And I think one of the things that perhaps was somewhat surprising in the data we saw at ASCO with the high rate of discontinuations for toxicity of Kisqali, especially with many patients still on therapy. So that number, of course, will go up with more follow-up.

我認為另一件事，丹在準備好的發言中提到了這一點，當然，過去有很多關於這兩種藥物耐受性差異的討論。我認為，我們在 ASCO 看到的數據中可能有些令人驚訝的一件事是，Kisqali 因毒性而停藥的比例很高，尤其是許多患者仍在接受治療。當然，隨著更多後續行動，這個數字將會上升。

So I think these 2 drugs, while they have different tolerability profiles in terms of what the side effects are, they actually have somewhat similar overall tolerance profiles. And importantly, the Verzenio tolerability can actually be managed with dose reductions without sacrificing efficacy. It's not clear that the same is true for Kisqali given the nature of those adverse events.

因此，我認為這兩種藥物雖然在副作用方面具有不同的耐受性，但實際上它們的總體耐受性有些相似。重要的是，Verzenio 的耐受性實際上可以通過減少劑量來控制，而不會犧牲療效。考慮到這些不良事件的性質，尚不清楚基斯卡利是否也是如此。

So we continue to feel really good about what Verzenio can offer to patients and its competitive profile in the marketplace, and that's been validated by -- in talks with prescribing physicians. So we continue to feel good, and we just got to make sure that all the patients who can benefit from the medicine know that it's out there for them.

因此，我們仍然對 Verzenio 可以為患者提供的服務及其在市場上的競爭地位感到非常滿意，這一點在與處方醫生的交談中得到了驗證。因此，我們繼續感覺良好，我們只需確保所有可以從該藥物中受益的患者都知道該藥物適合他們。

Thanks, Jake. Dave?

謝謝，傑克。戴夫？

Great. Well, we appreciate your participation in today's earnings call and your interest in the company. It's been a very productive first half of the year for Lilly, and we look forward to continuing our momentum into the second half. Thanks again for dialing in. And as always, please follow up with the IR team if you have questions we have not addressed on today's call. Have a great day.

偉大的。好吧，我們感謝您參加今天的財報電話會議以及您對公司的興趣。對於禮來公司來說，今年上半年是非常富有成效的，我們期待下半年繼續保持這種勢頭。再次感謝您撥通電話。與往常一樣，如果您有我們在今天的電話會議中未解決的問題，請與 IR 團隊聯繫。祝你有美好的一天。

Thank you, ladies and gentlemen. This does conclude our conference for today. This conference will be made available for replay beginning at 1 p.m. today running through August 21 at midnight. You may access the replay system at any time by dialing (800) 332-6854 and entering the access code 213952. International dialers can call (973) 528-0005. Again, those numbers are (800) 332-6854 and (973) 528-0005 with the access code 213952.

謝謝你們，女士們、先生們。我們今天的會議到此結束。該會議將於下午 1 點開始重播。今天一直持續到 8 月 21 日午夜。您可以隨時撥打 (800) 332-6854 並輸入訪問代碼 213952 訪問重播系統。國際撥號者可以撥打 (973) 528-0005。同樣，這些號碼是 (800) 332-6854 和 (973) 528-0005，接入碼為 213952。

Thank you for your participation. You may now disconnect your lines.

感謝您的參與。您現在可以斷開線路。