禮來公司 (LLY) 2018 Q1 法說會逐字稿

Ladies and gentlemen, thank you for standing by. Welcome to the Eli Lilly and Company Q1 2018 Earnings Call. (Operator Instructions) As a reminder, today's conference call is being recorded. (Operator Instructions)

女士們，先生們，謝謝你們的支持。歡迎參加禮來公司 2018 年第一季度財報電話會議。 （操作員說明）作為提醒，今天的電話會議正在錄音中。 （操作員說明）

I would now like to turn the conference over to Dave Ricks. Please go ahead.

我現在想把會議交給 Dave Ricks。請繼續。

Good morning. Thank you for joining us for Eli Lilly and Company's First Quarter 2018 Earnings Call. I'm Dave Ricks, Lilly's Chairman and CEO. Joining me on today's call are Josh Smiley, our Chief Financial Officer; Enrique Conterno, the President of Lilly Diabetes and Lilly U.S.A.; Dr. Sue Mahony, President of Lilly Oncology; Christi Shaw, President of Lilly Bio-Medicines; and Jeff Simmons, President of Elanco Animal Health. We're also joined by Kristina Wright, Jim Haney, Kevin Hern and Phil Johnson of the Investor Relations team.

早上好。感謝您參加禮來公司 2018 年第一季度財報電話會議。我是禮來公司董事長兼首席執行官戴夫·里克斯。加入我今天的電話會議的是我們的首席財務官 Josh Smiley； Enrique Conterno，禮來糖尿病和禮來美國公司總裁；禮來腫瘤學總裁 Sue Mahony 博士；禮來生物醫藥總裁 Christi Shaw；和 Elanco Animal Health 總裁 Jeff Simmons。投資者關係團隊的 Kristina Wright、Jim Haney、Kevin Hern 和 Phil Johnson 也加入了我們的行列。

We are also joined, for the first time, by Dan Skovronsky, our incoming President of Lilly Research Laboratories. Dan is succeeding Dr. Jan Lundberg, who retired at the end of May. Jan has been key to our success as we navigated the Years YZ and returned to growth with a series of successful products. We want to thank Jan for all his contributions to our company.

禮來研究實驗室即將上任的總裁 Dan Skovronsky 也首次加入了我們的行列。 Dan 將接替 5 月底退休的 Jan Lundberg 博士。 Jan 一直是我們成功的關鍵，因為我們在 YZ 歲月中導航並通過一系列成功的產品恢復增長。我們要感謝 Jan 對我們公司的所有貢獻。

During this conference call, we anticipate making projections and forward-looking statements based on our current expectations. Our actual results could differ materially due to a number of factors, including those listed on Slide 3 and those outlined in our latest forms 10-K and 10-Q filed with the Securities and Exchange Commission.

在這次電話會議期間，我們預計會根據我們目前的預期做出預測和前瞻性陳述。由於多種因素，我們的實際結果可能存在重大差異，包括幻燈片 3 中列出的因素以及我們向證券交易委員會提交的最新表格 10-K 和 10-Q 中概述的因素。

The information we provide about our products and pipeline is for the benefit of the investment community. It is not intended to be promotional, and it is not sufficient for prescribing decisions.

我們提供的有關我們的產品和管道的信息是為了投資界的利益。它不是為了促銷，也不足以做出處方決定。

2018 is off to a good start with first quarter revenue growth of 9%, which we leveraged into a 29% non-GAAP operating income growth, and 37% non-GAAP EPS growth. New pharmaceutical products continue to be the driver of our worldwide revenue growth, led by Trulicity, Basaglar, Jardiance and Taltz with growth in both the U.S. and international markets where our launches continue to scale up.

2018 年開局良好，第一季度收入增長 9%，我們將其用於非 GAAP 營業收入增長 29% 和非 GAAP 每股收益增長 37%。新醫藥產品繼續成為我們全球收入增長的驅動力，由 Trulicity、Basaglar、Jardiance 和 Taltz 領導，我們的產品在美國和國際市場都在增長，我們的產品在這些市場繼續擴大。

New product growth more than offset revenue declines, resulting from loss of exclusivity on a number of established products. In addition, we continue to expand our margins this quarter. Excluding the effects of FX on international inventory sold, non-GAAP gross margin as a percent of revenue increased by nearly 70 basis points over Q1 2017. And non-GAAP operating income as a percent of revenue increased by 775 basis points to 30.4%.

新產品的增長超過了收入下降的幅度，這是由於許多已建立的產品失去了排他性。此外，我們本季度繼續擴大利潤率。排除外匯對國際銷售庫存的影響，非公認會計準則毛利率佔收入的百分比比 2017 年第一季度增長了近 70 個基點。非公認會計準則營業收入佔收入的百分比增長了 775 個基點，達到 30.4%。

Pipeline progress this quarter also included approval and launch of an additional indication in first-line metastatic breast cancer for Verzenio, based on the MONARCH 3 data; positive Phase III studies of Taltz for ankylosing spondylitis, a positive Phase III study for Cyramza in high AFP patients with second-line liver cancer; and the initiation of a Phase III study for Trulicity in 3 and 4.5-milligram doses.

根據 MONARCH 3 的數據，本季度的管道進展還包括批准和推出 Verzenio 一線轉移性乳腺癌的額外適應症； Taltz 治療強直性脊柱炎的陽性 III 期研究，Cyramza 在二線肝癌高 AFP 患者中的陽性 III 期研究；並啟動 3 和 4.5 毫克劑量的 Trulicity 的 III 期研究。

While we are pleased that the FDA's Arthritis Advisory Committee supported the efficacy of both 2 milligrams and 4 milligrams of baricitinib in RA, and 2 milligrams overall, we are disappointed that the committee did not recommend approval of the 4-milligram dose. We are confident in the benefit risk profile of both baricitinib 2 milligrams and 4 milligrams for the treatment of patients with RA, supported by the clinical data generated to date and by the experience in more than 40 countries in which both doses are approved and available. We'll continue to work with the FDA on this important application.

雖然我們很高興 FDA 的關節炎諮詢委員會支持 2 毫克和 4 毫克巴瑞克替尼在 RA 中的療效，以及整體 2 毫克，但我們對委員會沒有建議批准 4 毫克劑量感到失望。我們對 2 毫克和 4 毫克巴瑞克替尼治療 RA 患者的益處風險狀況充滿信心，這得到了迄今為止產生的臨床數據和 40 多個國家/地區批准和使用兩種劑量的經驗的支持。我們將繼續與 FDA 合作處理這一重要應用。

In terms of capital deployment, we announced a strategic collaboration with Sigilon to develop encapsulated cell therapies for the treatment of type 1 diabetes. We purchased $1.1 billion of stock and returned nearly $600 million via the dividends. And we are making expected progress on our Elanco strategic review and still anticipate sharing our conclusions on our Q2 earnings call this July.

在資本配置方面，我們宣布與 Sigilon 達成戰略合作，開髮用於治療 1 型糖尿病的封裝細胞療法。我們購買了 11 億美元的股票，並通過股息返還了近 6 億美元。我們在 Elanco 戰略審查方面取得了預期的進展，並且仍然期待在今年 7 月的第二季度財報電話會議上分享我們的結論。

Slide 5 contains more detail on key events since our January earnings call.

幻燈片 5 包含了自 1 月份財報電話會議以來關鍵事件的更多詳細信息。

Now I'd like to turn the call over to Josh to review our Q1 results and provide an update on our financial guidance for 2018.

現在，我想將電話轉給 Josh，以審查我們的第一季度業績並提供我們 2018 年財務指導的最新信息。

Thanks, Dave. Slide 6 summarizes our presentation of GAAP results and non-GAAP measures, while Slide 7 provides a summary of our GAAP results. I'll focus my comments on our non-GAAP adjusted measures to provide insights into the underlying trends in our business, so please refer to today's earnings press release for a detailed description of the year-on-year changes in our first quarter GAAP results.

謝謝，戴夫。幻燈片 6 總結了我們對 GAAP 結果和非 GAAP 措施的介紹，而幻燈片 7 總結了我們的 GAAP 結果。我將把我的評論集中在我們的非 GAAP 調整措施上，以深入了解我們業務的潛在趨勢，因此請參閱今天的收益新聞稿，詳細描述我們第一季度 GAAP 業績的同比變化.

Looking at the non-GAAP measures on Slide 8, you'll see the revenue increase of 9% that Dave mentioned earlier. Gross margin as a percent of revenue decreased to 75.1%. This decrease was due to the effect of foreign exchange rates on international inventory sold. Excluding this FX effect, gross margin as a percent of revenue actually increased roughly 70 basis points, driven by higher realized prices and manufacturing efficiencies, partially offset by product mix.

查看幻燈片 8 上的非 GAAP 指標，您會看到 Dave 之前提到的 9% 的收入增長。毛利率佔收入的百分比下降至 75.1%。這一減少是由於外匯匯率對已售出的國際庫存的影響。排除這種外匯影響，毛利率佔收入的百分比實際上增加了大約 70 個基點，這是由於較高的實際價格和製造效率，部分被產品組合所抵消。

Total operating expense decreased 5% with marketing, selling and administrative expense decreasing 4% and R&D expense decreasing 6%. Total operating expense as a percent of revenue declined by 710 basis points compared to Q1 2017. This significant improvement reflects our continued efforts to reduce our cost structure and increase our margins, accelerated by the restructuring actions we took late last year.

總運營費用下降 5%，營銷、銷售和管理費用下降 4%，研發費用下降 6%。與 2017 年第一季度相比，總運營費用佔收入的百分比下降了 710 個基點。這一顯著改善反映了我們在去年底採取的重組行動加速了降低成本結構和提高利潤率的持續努力。

Other income and expense was income of $67.5 million this quarter compared to income of $78.3 million in last year's quarter. Our tax rate was 15.9%, a decrease of 530 basis points compared with the same quarter last year, driven primarily by the impact of U.S. tax reform. At the bottom line, net income increased 35%, while earnings per share increased slightly faster at 37% due to a reduction in shares outstanding from shares repurchased.

其他收入和支出是本季度的收入為 6750 萬美元，而去年同期的收入為 7830 萬美元。我們的稅率為 15.9%，與去年同期相比下降了 530 個基點，主要受美國稅制改革的影響。歸根結底，淨收入增長了 35%，而由於回購股票的流通股減少，每股收益增長略快，達到 37%。

We achieved this significant earnings growth by delivering high single-digit revenue growth while significantly reducing our operating expenses, creating positive leverage again this quarter.

我們通過實現高個位數的收入增長，同時顯著降低我們的運營費用，實現了這一顯著的盈利增長，本季度再次創造了正槓桿。

Slide 9 provides the reconciliation between reported and non-GAAP EPS. You'll find additional details on these adjustments on Slide 20.

幻燈片 9 提供了報告的和非 GAAP 每股收益之間的對賬。您將在幻燈片 20 上找到有關這些調整的更多詳細信息。

So moving to Slide 10, let's take a look at the effect of price, rate and volume on revenue growth. This quarter, the effective foreign exchange provided a 4 percentage point benefit. Excluding this, our worldwide revenue growth on a performance basis was 5%, driven by both price and volume. For a fifth straight quarter, our human pharma business drove volume growth in each major geography. U.S. pharma revenue increased 10%, driven by price and, to a lesser extent, volume. Our diabetes portfolio, led by Trulicity, Basaglar and Jardiance, was the primary driver of volume growth with growth of 30%, offset by the losses of exclusivity for Strattera, Effient and Axiron, and by a decline in volume for Cialis, due to the entry of generic erectile dysfunction products.

所以轉到幻燈片 10，讓我們來看看價格、費率和數量對收入增長的影響。本季度，有效外匯提供了 4 個百分點的收益。不包括這一點，在價格和數量的推動下，我們在業績基礎上的全球收入增長為 5%。連續第五個季度，我們的人類製藥業務推動了每個主要地區的銷量增長。美國製藥公司的收入增長了 10%，這主要是受價格推動，其次是銷量。我們的糖尿病產品組合由 Trulicity、Basaglar 和 Jardiance 領導，是銷量增長的主要驅動力，增長了 30%，但被 Strattera、Effient 和 Axiron 的排他性損失以及 Cialis 的銷量下降所抵消，原因是通用勃起功能障礙產品的進入。

For U.S. pharma, it's also worth noting that when excluding LOEs, the rest of our U.S. products grew by approximately 20% in total. U.S. price growth in the quarter was favorably impacted by an adjustment for rebates and discounts, primarily related to lower Medicaid utilization than anticipated across the portfolio.

對於美國製藥公司來說，還值得注意的是，如果不包括 LOE，我們其餘的美國產品總共增長了約 20%。本季度美國價格增長受到回扣和折扣調整的有利影響，這主要與整個投資組合的醫療補助利用率低於預期有關。

While Medicaid remains a significant segment of our U.S. business, we estimate that the growth we experienced in this segment in the past several years has plateaued in recent months.

雖然醫療補助仍然是我們美國業務的重要組成部分，但我們估計過去幾年我們在這一領域的增長在最近幾個月已經趨於平穩。

Moving to Europe, we've been pleased with the overall performance of our new product portfolio across the region. Pharma revenue grew 2% excluding net FX, driven entirely by volume despite the loss of exclusivity for Cialis. Excluding the impact of the Cialis LOE, volume grew nearly 17%. This volume growth was led by Trulicity, Olumiant, Taltz, Lartruvo, Jardiance and Basaglar.

搬到歐洲後，我們對我們新產品組合在該地區的整體表現感到滿意。儘管 Cialis 失去了獨家經營權，但不包括淨外彙在內的醫藥收入增長了 2%，這完全是由銷量推動的。排除 Cialis LOE 的影響，銷量增長了近 17%。這一銷量增長由 Trulicity、Olumiant、Taltz、Lartruvo、Jardiance 和 Basaglar 引領。

In Japan, pharma revenue increased 1% excluding net FX, driven by volume of new products namely Trulicity, Taltz and Jardiance, with a partial offset in price from the impact of the biannual price cuts.

在日本，由於新產品（即 Trulicity、Taltz 和 Jardiance）數量的推動，不包括淨外彙在內的製藥收入增長了 1%，但價格部分抵消了一年兩次降價的影響。

Our pharma revenue in the rest of the world increased 4% on a performance basis this quarter, led by volume growth of Trulicity, Humalog and Forteo.

本季度我們在世界其他地區的製藥收入增長了 4%，這主要得益於 Trulicity、Humalog 和 Forteo 的銷量增長。

Turning to animal health. As we noted during our Q4 earnings call, we've been expecting to return to top line growth in the second half of this year, and our Q1 results are on track with this expectation. Excluding FX, Elanco revenue declined 4% this quarter. I'd highlight, however, that revenue in Q1 actually increased 1% in performance terms when excluding the impact of products we've made the strategic decision to exit. These strategic exits are the contract manufacturing activity that came with the BI U.S. vaccines acquisition as well as 2 terminated legacy U.S. distribution agreements and Posilac. You'll see that we've provided a backup slide quantifying the drivers of our animal health revenue growth, excluding those strategic exits.

轉向動物健康。正如我們在第四季度財報電話會議中指出的那樣，我們一直預計今年下半年將恢復營收增長，我們的第一季度業績符合這一預期。不包括外匯，Elanco 本季度收入下降 4%。然而，我要強調的是，如果排除我們做出退出戰略決定的產品的影響，第一季度的收入實際上增長了 1%。這些戰略性退出是 BI 美國疫苗收購以及 2 項終止的美國傳統分銷協議和 Posilac 帶來的合同製造活動。您會看到我們提供了一張備用幻燈片，量化了我們動物健康收入增長的驅動因素，不包括那些戰略性退出。

We're encouraged with the revenue trends we're seeing in our ongoing or core business. New products contribute $62 million in Q1, driven primarily by Credelio, INTERCEPTOR PLUS and Galliprant. These new products drove our core companion animal portfolio up 10% in the quarter.

我們對我們正在進行的或核心業務中看到的收入趨勢感到鼓舞。新產品在第一季度貢獻了 6200 萬美元，主要由 Credelio、INTERCEPTOR PLUS 和 Galliprant 推動。這些新產品推動我們的核心伴侶動物產品組合在本季度增長了 10%。

Our core food animal business decreased 4%, primarily due to U.S. buying patterns in Q1 2017 as well as continued ractopamine competition. Importantly though, our poultry business continue to deliver strong growth. In Q1, poultry products grew 11%, well ahead of the market and we expect to see full year growth for our overall core food animal portfolio.

我們的核心食用動物業務下降了 4%，主要是由於 2017 年第一季度美國的購買模式以及萊克多巴胺的持續競爭。但重要的是，我們的家禽業務繼續實現強勁增長。第一季度，家禽產品增長了 11%，遠遠領先於市場，我們預計我們的整體核心食用動物產品組合將全年增長。

Lastly, I'd point out, this is our second consecutive quarter with overall price growth, which is the sign of solid foundations in the industry. We expect this price growth to continue through 2018.

最後，我要指出，這是我們連續第二個季度整體價格增長，這是行業基礎穩固的標誌。我們預計這種價格增長將持續到 2018 年。

We are monitoring the trade situation closely and while we do not see immediate impact to our animal health business, we are cautious about the broader economic impact with export activity declines. Hopefully, this provides you with useful insights into our animal health revenue growth, and Jeff can address questions you may have in the Q&A session.

我們正在密切關注貿易形勢，雖然我們沒有看到對我們的動物保健業務的直接影響，但我們對出口活動下降帶來的更廣泛的經濟影響持謹慎態度。希望這能為您提供有關我們動物健康收入增長的有用見解，並且 Jeff 可以解決您在問答環節中可能遇到的問題。

Now let's take a look at the drivers of our worldwide volume growth on Slide 11. In total, our newer products, including Trulicity, Basaglar, Jardiance, Taltz, Verzenio, Olumiant, Lartruvo and Cyramza were the engine of our worldwide volume growth. You can see that these products drove 11.1 percentage points of volume growth this quarter. The loss of exclusivity of Effient, Strattera, Zyprexa, Cymbalta, Evista and Axiron provided a drag of 510 basis points, while Cialis and animal health accounted for 230 and 120 basis points of volume decline, respectively.

現在讓我們在幻燈片 11 上看一下我們全球銷量增長的驅動因素。總的來說，我們的新產品，包括 Trulicity、Basaglar、Jardiance、Taltz、Verzenio、Olumiant、Lartruvo 和 Cyramza 是我們全球銷量增長的引擎。您可以看到，這些產品在本季度推動了 11.1 個百分點的銷量增長。 Effient、Strattera、Zyprexa、Cymbalta、Evista 和 Axiron 排他性的喪失拖累了 510 個基點，而 Cialis 和動物健康分別導致銷量下降 230 個和 120 個基點。

Slide 12 provides a view of our new product uptake. In total, these brands generated nearly $1.5 billion in revenue this quarter and represented over a quarter of our total worldwide revenue.

幻燈片 12 提供了我們新產品吸收的視圖。總的來說，這些品牌在本季度創造了近 15 億美元的收入，占我們全球總收入的四分之一以上。

I'd like to highlight the progress in our second quarter of Verzenio launch. We are pleased with the continued new-to-brand share growth, which is now at 15%, and the approval of the new first-line metastatic breast cancer indication, giving us the broadest label in the class.

我想強調一下我們第二季度推出 Verzenio 的進展情況。我們對新品牌份額的持續增長（目前為 15%）以及新的一線轉移性乳腺癌適應症的批准感到高興，這為我們提供了同類產品中最廣泛的標籤。

Lastly, at AACR, we presented the final analysis of the MONARCH 3 data, which showed 28.2 months of progression-free survival, more than 13 months better than placebo as well as an analysis across all patient subgroups in the MONARCH 2 and MONARCH 3 studies, which demonstrated that patients with certain concerning clinical characteristics receive substantial benefits from the addition of Verzenio to endocrine therapy.

最後，在 AACR，我們展示了 MONARCH 3 數據的最終分析，顯示 28.2 個月的無進展生存期，比安慰劑好 13 個月以上，以及對 MONARCH 2 和 MONARCH 3 研究中所有患者亞組的分析，這表明具有某些相關臨床特徵的患者從將 Verzenio 添加到內分泌治療中獲得了顯著的益處。

Moving to Slide 13. This quarter, FX had a more significant effect on our results largely driven by the euro. Excluding FX, you can see that revenue increased 5%, non-GAAP cost of sales increased just 2% and non-GAAP EPS increased 47%.

轉到幻燈片 13。本季度，外匯對我們的業績產生了更顯著的影響，主要受歐元驅動。不包括外匯，您可以看到收入增長了 5%，非 GAAP 銷售成本僅增長了 2%，非 GAAP 每股收益增長了 47%。

Turning to our 2018 financial guidance on Slide 14, you will see that we've updated our guidance to reflect an additional $700 million on the top line, driven by lower expected Medicaid utilization, changes and estimates to rebates and discounts as well as the impact of foreign exchange rate movements.

轉到我們在幻燈片 14 上的 2018 年財務指導，您會看到我們已經更新了我們的指導，以反映額外的 7 億美元的收入，這是由於預期的醫療補助使用率降低、回扣和折扣的變化和估計以及影響的匯率變動。

A slight increase in marketing, selling, admin and R&D expenses to account for FX movements as well as for funding for additional pipeline opportunities. An increase of $25 million to the top end of our range for OID and a decrease in our tax rate from 18% to 17%, which reflects the change in expected geographic mix of income. These updates contribute to an increase in both GAAP and non-GAAP earnings per share. Our non-GAAP earnings per share is now expected to be $5.10 to $5.20, which is an increase of 20% over 2017 at the midpoint of the range.

營銷、銷售、管理和研發費用略有增加，以說明外匯變動以及為額外管道機會提供資金。我們的 OID 範圍上限增加了 2500 萬美元，我們的稅率從 18% 降低到 17%，這反映了預期收入地理組合的變化。這些更新有助於提高 GAAP 和非 GAAP 每股收益。我們的非公認會計原則每股收益現在預計為 5.10 美元至 5.20 美元，比 2017 年在該範圍的中點增長 20%。

Now I will turn the call back over to Dave to review the pipeline and key future events.

現在，我將把電話轉回給 Dave，以審查管道和未來的關鍵事件。

Thanks, Josh. Slide 15 shows select NMEs and NILEX as of April 20. Movements since our last earnings call include: the approval of Verzenio for the first-line treatment of metastatic breast cancer in the U.S.; a Phase III start for Trulicity in 3 and 4.5-milligram doses; a Phase I start for the IL-23 CGRP biospecific antibody for immunology. While we had attrition of the Phase II BACE inhibitor molecule as monotherapy, the trial, in combination with the N3pG antibody continues and we look forward to seeing results in this novel trial design.

謝謝，喬希。幻燈片 15 顯示了截至 4 月 20 日的部分 NME 和 NILEX。自我們上次財報電話會議以來的變動包括： Verzenio 批准用於美國轉移性乳腺癌的一線治療； 3 和 4.5 毫克劑量的 Trulicity 的 III 期開始；用於免疫學的 IL-23 CGRP 生物特異性抗體的第一階段開始。雖然我們已經淘汰了 II 期 BACE 抑製劑分子作為單一療法，但該試驗與 N3pG 抗體的組合仍在繼續，我們期待在這一新的試驗設計中看到結果。

We also discontinued our abemaciclib pancreatic cancer study. You'll see we've combined our NME and NILEX pipeline into 1 view. In terms of NILEX, we have a robust set of lifecycle opportunities for our recently launched products, which we expect will continue to bolster the growth prospects from important brands like Trulicity, Taltz, Verzenio, Olumiant and Jardiance. These products are well positioned in some of the largest and fastest-growing categories and are addressing areas of high unmet medical need.

我們還終止了我們的 abemaciclib 胰腺癌研究。您會看到我們已將 NME 和 NILEX 管道合併到一個視圖中。就 NILEX 而言，我們最近推出的產品擁有一系列強大的生命週期機會，我們預計這將繼續支持 Trulicity、Taltz、Verzenio、Olumiant 和 Jardiance 等重要品牌的增長前景。這些產品在一些最大和增長最快的類別中處於有利地位，並正在解決高度未滿足的醫療需求領域。

Key NILEX opportunities include AxSpA for Taltz, atopic dermatitis for Olumiant, adjuvant breast cancer for Verzenio, the 3 and 4.5-milligram dose study for Trulicity and heart failure for Jardiance, which is in collaboration with Boehringer Ingelheim.

NILEX 的主要機會包括用於 Taltz 的 AxSpA、用於 Olumiant 的特應性皮炎、用於 Verzenio 的輔助乳腺癌、用於 Jardiance 的 3 和 4.5 毫克劑量研究以及與勃林格殷格翰合作的 Jardiance 心力衰竭。

On Slide 16, we highlight expected key events for 2018. In addition to noting the U.S. approval of Verzenio for first-line metastatic breast cancer, we've indicated the data disclosure of the KEYNOTE-189 study at AACR, which shows that Alimta, in combination with Keytruda plus platinum chemotherapy reduced the risk of death by half compared with chemotherapy alone as first-line treatment in metastatic non-squamous non-small cell lung cancer patients. The overall survival benefit was robust regardless of PD-L1 expression status.

在幻燈片 16 上，我們強調了 2018 年的預期關鍵事件。除了注意到美國批准 Verzenio 用於一線轉移性乳腺癌外，我們還指出了 AACR 的 KEYNOTE-189研究的數據披露，這表明 Alimta，作為轉移性非鱗狀非小細胞肺癌患者的一線治療，與單獨化療相比，與 Keytruda 聯合鉑類化療相比，死亡風險降低了一半。無論 PD-L1 表達狀態如何，總體生存獲益都是穩健的。

We also announced last week that the Cyramza Phase III study in bladder cancer did not reach statistical significance in the secondary endpoint of overall survival. There are many events to look forward to in 2018, notably, the expected regulatory action for U.S. baricitinib, galcanezumab, Verzenio and Alimta. We also look forward to the data readout of the second Phase III study of Taltz in ankylosing spondylitis. The readout of the REWIND study for Trulicity and the initiation of several Phase III studies, including our anti-IL-23 mirikizumab for psoriasis and ulcerative colitis.

我們上週還宣布，膀胱癌的 Cyramza III 期研究在總生存期的次要終點沒有達到統計學意義。 2018 年有許多值得期待的事件，特別是美國巴瑞克替尼、加卡尼單抗、Verzenio 和 Alimta 的預期監管行動。我們也期待著 Taltz 在強直性脊柱炎中的第二個 III 期研究的數據讀出。對 Trulicity 的 REWIND 研究的讀數和幾項 III 期研究的啟動，包括我們用於銀屑病和潰瘍性結腸炎的抗 IL-23 mirikizumab。

Before we go to the Q&A session, let me briefly sum up the progress we've made this quarter. In Q1, new products accounted for 25% of total revenue, and nearly 30% of our human pharma revenue. Volume grew in our human pharma business by 4% despite recent patent expirations. And when excluding the strategic exits, our animal health business returned a positive performance growth. We realized significant efficiencies in our cost structure, leading to operating margin expansion of 775 basis points, excluding FX. And we have made pipeline progress this quarter with the launch of Verzenio in the first-line metastatic breast cancer in the U.S., the launch of Taltz for psoriatic arthritis in Germany and positive Phase III data for new indications for both Taltz and Cyramza.

在我們進入問答環節之前，讓我簡要總結一下我們本季度取得的進展。第一季度，新產品佔總收入的 25%，占我們人類製藥收入的近 30%。儘管最近專利到期，但我們的人類製藥業務量增長了 4%。剔除戰略性退出後，我們的動物保健業務實現了正向業績增長。我們實現了成本結構的顯著效率，導致營業利潤率擴大了 775 個基點，不包括外匯。我們在本季度取得了進展，在美國推出 Verzenio 用於一線轉移性乳腺癌，在德國推出 Taltz 治療銀屑病關節炎，以及 Taltz 和 Cyramza 新適應症的積極 III 期數據。

Finally, we returned $1.7 billion to shareholders via the dividend and share repurchase.

最後，我們通過股息和股票回購向股東返還了 17 億美元。

This concludes our prepared remarks. Now I'll turn the call over to Phil Johnson to moderate the Q&A session.

我們準備好的評論到此結束。現在我將把電話轉給 Phil Johnson 來主持問答環節。

Thank you, Dave. (Operator Instructions) Leaha, if you could provide the instructions for the Q&A session, and then we're ready for the first caller.

謝謝你，戴夫。 （操作員說明）Leaha，如果您能提供問答環節的說明，那麼我們就可以接聽第一個來電者了。

(Operator Instructions) And our first question is from the line of Gregg Gilbert with Deutsche Bank.

（操作員說明）我們的第一個問題來自德意志銀行的 Gregg Gilbert。

First Dan, congrats to you on your new role. Dave, can you talk about the use of bari outside the U.S. in terms of mix of strengths? And any post-marketing safety data that you have to bolster your case with the FDA? And secondly, on the subject of drug pricing in the U.S., what types of changes are you expecting the administration to put forth? You can be as specific as you'd like, but at least conceptually, would love your opinion. And how do you think Lilly is positioned relative to those potential changes?

丹第一，祝賀你擔任新職務。戴夫，你能談談在美國以外使用巴里的優勢嗎？以及您必須支持 FDA 的任何上市後安全數據？其次，關於美國的藥品定價問題，您希望政府提出哪些類型的改變？您可以隨心所欲地具體化，但至少在概念上，您會喜歡您的意見。您如何看待禮來相對於這些潛在變化的定位？

Great, Gregg. Thank you for the question. We're actually going to have Christi Shaw, President of Lilly Bio-Meds take your question on the use of the 2 different doses outside the U.S. and the OUS data that may be helpful as we present our case to the FDA. And then Dave, you'll have the question on drug pricing. Christi?

太好了，格雷格。感謝你的提問。實際上，我們將請禮來生物醫藥總裁 Christi Shaw 回答您關於在美國以外使用 2 種不同劑量的問題，以及在我們向 FDA 提交我們的案例時可能有幫助的 OUS 數據。然後是戴夫，你會有關於藥品定價的問題。克里斯蒂?

So outside the U.S., in over 40 countries, we have both the 2 and the 4-milligram approved and the majority of the use is in the 4-milligram with remarkable efficacy. Really patients getting their lives back and the safety continues to hold up that we see no new signals that are different than what we submitted to the FDA. And we'll continue, I think, yesterday's AdCom showed for sure the unanimous vote on the efficacy of the 4 milligrams is important to patients in the U.S., so we want both the 2 and the 4 milligrams approved in the U.S. for those patients.

因此，在美國以外的 40 多個國家/地區，我們同時批准了 2 和 4 毫克，並且大部分使用在 4 毫克中，具有顯著的功效。真正的患者恢復了他們的生命並且安全性繼續保持，我們沒有看到與我們提交給 FDA 的不同的新信號。我認為，我們將繼續下去，昨天的 AdCom 肯定地表明，一致投票決定 4 毫克的療效對美國的患者很重要，所以我們希望在美國為這些患者批准 2 毫克和 4 毫克。

Thank you, Christi. Dave?

謝謝你，克里斯蒂。戴夫？

Yes. Thanks, Gregg. Obviously, big topic, drug pricing. I mean, it's hard to speculate exactly what the administration will say or do, but I think I can comment on what pharma's position is on this and Lilly's as well, which is as it relates to a leading pain at the pharmacy counter and reducing the burden of list prices that consumers pay at the counter, we've been -- long been proponents of rebate passthrough, both in commercial plans and Part D. And I think the most important action that the administration could take would be to create either a set of experiments or a mandate, a rebate passthrough for patients in the Part D program. This would, I think, immediately impact seniors' cash flow and pocketbook as well as, I think, help to normalize the incentives on gross to net spreads. So that I would be -- personally be surprised if that wasn't part of the commentary, and that's something we've long stood for. So that would be I think a positive development from our perspective. The HHS secretary has commented on Part D and the lack of market mechanism there. I would expect that to be a topic of discussion. And then we do see an increased desire under this administration to approve waivers for Medicaid giving states flexibility in variety of forms to manage their own programs. And I would expect to see more of that. Finally, we worked closely with this administration on trade agenda to balance the incentives that foreign markets have to suppress drug pricing which are primarily exports from the U.S. We've had some early signs of success there with the Korea free trade agreement. And we'll keep on that, I think long-term, U.S. needs to use its trading power to help equalize that sharing across, sort of amortizing the R&D expense that it takes to create the new innovations which are coming even more frequently from the industry. So we'll watch that carefully and continue to advocate for pro-innovation, pro-patient choice as well as policies that can make sure that this innovation -- this industry can continue to innovate and prosper for years to come. So all those topics are front of mind and we'll keep working up with them, Gregg.

是的。謝謝，格雷格。顯然，大話題，藥品定價。我的意思是，很難準確推測政府會說什麼或做什麼，但我想我可以評論製藥公司和禮來公司在這方面的立場，因為這與藥房櫃檯的主要痛苦和減少消費者在櫃檯支付的標價負擔，我們一直是 - 長期以來，無論是在商業計劃還是在 D 部分中，都支持回扣傳遞。我認為政府可以採取的最重要的行動是創建一個一組實驗或任務，D 部分計劃中患者的回扣傳遞。我認為，這將立即影響老年人的現金流和錢包，並且我認為有助於使毛利與淨利差的激勵措施正常化。因此，如果這不是評論的一部分，我個人會感到驚訝，這是我們長期以來所堅持的。因此，從我們的角度來看，我認為這是一個積極的發展。 HHS 部長評論了 D 部分以及那裡缺乏市場機制。我希望這會成為討論的話題。然後我們確實看到本屆政府越來越希望批准醫療補助的豁免，讓各州以各種形式靈活管理自己的計劃。我希望看到更多。最後，我們在貿易議程上與本屆政府密切合作，以平衡外國市場必須抑制主要從美國出口的藥品定價的激勵措施。我們已經在韓國自由貿易協定方面取得了一些成功的早期跡象。我們將繼續這一點，我認為從長遠來看，美國需要利用其貿易力量來幫助平衡這種分享，在某種程度上分攤研發費用，以創造更頻繁地來自美國的新創新。行業。因此，我們將仔細觀察並繼續倡導支持創新、支持患者的選擇以及可以確保這種創新的政策——這個行業可以在未來幾年繼續創新和繁榮。 Gregg，所有這些話題都在腦海中，我們將繼續與他們合作。

It's the line of John Boris with SunTrust.

這是 SunTrust 的 John Boris 的產品線。

Just back to Olumiant, can you just quantify the number of patient years of therapy that you have on Olumiant, not just in the clinical package, but how many or how much patient years or number of patient years of therapy that you have abroad, especially since it's heavily skewed towards the 4-milligram? And then on Taltz, on the Novartis call, they clearly indicated that they also had a wholesaler destock with Tremfya. In addition to that was giving away a lot of free products. And then obviously, co-pay accumulators are also a topic that are penalizing patients on deductibles. Can you provide some commentary on the miss on Taltz? And the impact across your business of potentially co-pay accumulators going forward?

回到Olumiant，您能否僅量化您在Olumiant上的患者治療年數，不僅僅是在臨床包中，而是您在國外有多少或多少患者年或患者年數，尤其是因為它嚴重偏向 4 毫克？然後在 Taltz 上，在諾華電話會議上，他們明確表示他們還與 Tremfya 有一家批發商去庫存。除此之外，還贈送了很多免費產品。然後很明顯，共同支付累加器也是一個在免賠額上懲罰患者的話題。你能對 Taltz 的小姐發表一些評論嗎？以及未來潛在的共同支付累加器對您的業務的影響？

Great, John. Thank you for the questions. So Christi, if you want to start with Taltz question, and then we'll figure out who's going to be in the best position here to give some of the numbers on the patient years exposures for Olumiant in the clinical trial program.

太好了，約翰。謝謝你的提問。所以克里斯蒂，如果你想從 Taltz 的問題開始，然後我們將找出誰將在這里處於最佳位置，以提供 Oluminant 在臨床試驗計劃中的患者年暴露量的一些數字。

And can you give me the clarity on the Taltz question? It was with Tremfya?

你能給我澄清一下 Taltz 的問題嗎？是和Tremfya一起的嗎？

It seems Novartis indicated they gave away a lot of free product through initial sampling. How much of that impact IL-17 uptake in the quarter, particularly Taltz?

諾華似乎表示他們通過初始樣品贈送了很多免費產品。這對本季度 IL-17 的吸收有多大影響，尤其是 Taltz？

So for Taltz, we did have some inventory changes which was the biggest rationale for our decline from Q4 to Q1 in terms of dollars. But our demand was up in terms of Q4 to Q1. And in fact, our NBRx has grown 30%, sequentially, in the first quarter. So we're seeing actually real demand coming through. I can't really comment on the others and how they count their inventories. The accumulator program, I think, our goal is to make sure that patients get access to every medicine that we provide and that their doctors think they need. So, whether that's a little bit of rebating, whether that's co-pay assistance, et cetera, that passthrough that Dave talked about earlier is also important to ensure the patients get access. But we haven't had issues to date.

因此，對於 Taltz，我們確實有一些庫存變化，這是我們從第四季度到第一季度以美元計算下降的最大原因。但我們的需求在第四季度到第一季度有所上升。事實上，我們的 NBRx 在第一季度環比增長了 30%。因此，我們看到了真正的需求。我無法真正評論其他人以及他們如何計算庫存。我認為，累加器計劃的目標是確保患者能夠獲得我們提供的每一種藥物，並且他們的醫生認為他們需要。因此，無論這是否是一點回扣，是否是共同支付援助等等，戴夫之前談到的這種通過對於確保患者獲得訪問權也很重要。但到目前為止，我們還沒有遇到任何問題。

And then John, I don't think in the room, we have numbers on the patients that are in some of the overseas registries for follow-up. I think Dan, you do have some information on the clinical trial program and the number of patients and patient years exposures.

然後約翰，我不認為在會議室裡，我們有一些海外登記處的患者數字以進行隨訪。我認為丹，您確實有一些關於臨床試驗計劃以及患者數量和患者年暴露量的信息。

Yes. Thanks, John. So, in the safety data we presented to the advisory committee was based on more than 7,800 patient years in our clinical trials, and that establishes the safety database for baricitinib from clinical trial experience. Your question referred also to the commercial experience outside the United States or obviously, there have been many, many more patients exposed the drug. Although we don't have exact numbers for patient-year exposure, as you heard from Christi, despite that extensive exposure, we haven't seen any new safety signals. So while we agreed that VTE is a potential risk of this drug, we haven't seen that manifest in the clinical experience.

是的。謝謝，約翰。因此，在我們提交給諮詢委員會的安全性數據中，我們基於 7,800 多名患者年的臨床試驗，從臨床試驗經驗中建立了巴瑞替尼的安全性數據庫。你的問題還提到了美國以外的商業經驗，或者顯然，有很多很多的患者接觸了這種藥物。儘管我們沒有患者年暴露的確切數字，正如您從克里斯蒂那裡聽到的那樣，儘管有大量暴露，但我們還沒有看到任何新的安全信號。因此，雖然我們同意 VTE 是這種藥物的潛在風險，但我們還沒有在臨床經驗中看到這一點。

That is the line of Tim Anderson with Bernstein.

這是蒂姆安德森與伯恩斯坦的路線。

A couple of questions. Going back to Taltz. So, in the class of the IL-17, in general, J&J is running the Phase 3 ECLIPSE trial comparing their IL-23 to Novartis' IL-17. You have both of these mechanisms either on the market or in development. So I'm hoping you'll have some perspective on what you think is the better, more effective mechanism in psoriasis. And if that J&J trial comes out in favor of Tremfya, doesn't that have a potential and direct impact on Taltz? And second question on your GIP/GLP-1, I know you've said in the past we're supposed to see Phase II data this year. Can you say what the likely venue will be? And maybe preview what you're hoping to see in that data?

幾個問題。回到塔爾茲。因此，一般來說，在 IL-17 類別中，強生正在進行第三階段 ECLIPSE 試驗，將他們的 IL-23 與諾華的 IL-17 進行比較。無論是在市場上還是在開發中，您都擁有這兩種機制。所以我希望你能對你認為的牛皮癬更好、更有效的機制有一些看法。如果 J&J 的試驗結果支持 Tremfya，那這不是對 Taltz 產生潛在的直接影響嗎？關於您的 GIP/GLP-1 的第二個問題，我知道您過去說過我們應該在今年看到 II 期數據。你能說一下可能的場地是什麼嗎？也許可以預覽您希望在該數據中看到的內容？

Great, Tim, thank you for the questions. So Christi, to you for the question on Taltz IL-23 versus IL-17. And then Enrique, over to you for your first question of the day on the GIP/GLP.

太好了，蒂姆，謝謝你的提問。所以克里斯蒂，關於 Taltz IL-23 與 IL-17 的問題。然後是 Enrique，請您回答當天關於 GIP/GLP 的第一個問題。

Sure, I mean, first of all, what I would say is thank goodness for patients, we have so many more newer medications that are providing such higher efficacy, so IL-23, IL-17s are going to be great for patients. And it's going to kind of tap into that older market where the older TNFs really lack efficacy, relatively speaking. So the other thing is patients really turn through different modality. Each patient might need something different, they respond to one, and not the other, so we're really confident and glad that we have both in our portfolio and we believe there will be specific patients for each. Specific to Taltz, as we look at the future and the very short-term, not only is the psoriatic arthritis indication starting to takeoff, psoriasis dermatology, really move in the first quarter and we think it's due to the psoriatic arthritis indication really solidifying that efficacy there. But we also have our own head-to-head in psoriatic arthritis, it readouts later this year versus Humira. And then we have our ankylosing spondylitis data too that we have one of 2 studies that have completed, the second one will be at the end of this year. So a lot's happening with Taltz and we feel very good about our chances of winning the marketplace.

當然，我的意思是，首先，我要說的是感謝患者，我們有很多更新的藥物可以提供如此高的療效，因此 IL-23、IL-17 對患者來說將非常有用。相對而言，它將進入舊的 TNF 確實缺乏功效的舊市場。所以另一件事是患者真的通過不同的方式轉變。每個患者可能需要不同的東西，他們會回應一個，而不是另一個，所以我們非常自信和高興我們的投資組合中都有這兩個，我們相信每個人都會有特定的患者。具體到 Taltz，當我們展望未來和非常短期的時候，不僅銀屑病關節炎適應症開始起飛，銀屑病皮膚病學在第一季度真正移動，我們認為這是由於銀屑病關節炎適應症真正鞏固了那裡的功效。但我們在銀屑病關節炎方面也有自己的正面交鋒，今年晚些時候將與 Humira 進行對比。然後我們也有我們的強直性脊柱炎數據，我們已經完成了兩項研究中的一項，第二項將在今年年底完成。因此，Taltz 發生了很多事情，我們對贏得市場的機會感到非常滿意。

Thank you, Christi. Enrique?

謝謝你，克里斯蒂。恩里克?

So we've been excited for quite some time about GIP/GLP. Clearly, the hurdle for this product is pretty high, and we want to see superior outcomes when it comes to hemoglobin A1c, and weight loss, vis-à-vis current GLPs. We expect that we are going to be disclosing some of this data either later, late this year or at ADA next year. We'll have to see.

因此，我們對 GIP/GLP 感到興奮已經有一段時間了。顯然，該產品的障礙相當高，我們希望看到在血紅蛋白 A1c 和體重減輕方面與目前的 GLP 相比取得更好的成果。我們預計我們將在今年晚些時候或今年晚些時候或明年在 ADA 上披露其中的一些數據。我們得看看。

Next, we have the line of Geoff Meacham from Barclays.

接下來，我們有來自巴克萊的 Geoff Meacham 產品線。

I just have a few more for Enrique in diabetes. So Trulicity growth has been great, but how influential do you feel like REWIND could be, positive or negative, relative to the current trajectory? And then Jardiance SLT 2 class is growing, but we haven't quite seen a tipping point for Jardiance despite guidelines. How do you think that could play out? What do you think that could be? And then I know there's been a lot of bari questions already, but if it's just the 2 mg dose that's approved, maybe help us with the commercial positioning, obviously, weaker, but I would just want to get your context for that.

我還有幾個給恩里克治療糖尿病的。因此，Trulicity 的增長非常好，但是相對於當前的軌跡，您覺得 REWIND 的影響力有多大，無論是正面的還是負面的？然後 Jardiance SLT 2 類正在增長，但儘管有指導方針，我們還沒有完全看到 Jardiance 的轉折點。你認為這會如何發展？你認為那可能是什麼？然後我知道已經有很多巴里問題，但如果只是批准了 2 毫克劑量，也許可以幫助我們的商業定位，顯然，更弱，但我只想了解你的背景。

Great, Geoff. Thank you for the questions. Enrique, we'll go to you for the first two questions for Trulicity and Jardiance. And then Christi, over to you for the question on the 2 mg dose for baricitinib and commercial implication.

太好了，傑夫。謝謝你的提問。 Enrique，我們將向您解答關於 Trulicity 和 Jardiance 的前兩個問題。然後克里斯蒂，關於巴瑞替尼的 2 毫克劑量和商業意義的問題交給你了。

Yes. Maybe just to start with framing the Trulicity quarter, because we have another strong quarter, continued solid growth. We basically have seen that the increased promotion by the new launches is basically having some impact in market acceleration, but we see both. We see a very good market growth, and we see, basically, a good share performance with Trulicity in a more competitive environment. So we very much like our position. We have a strong access position as well. And finally, and probably something that, sometimes, is underestimated by it's the patient experience that we basically receive from physicians, from patients themselves. We have an excellent real-world efficacy, which is very simply delivered. So we're very excited about that. Clearly, REWIND doesn't change any of that, but it is extremely important because we believe, the longer term for us to be competitive in this class, we will need cardiovascular outcomes. As it relates to the SGLT2s, clearly, we have been seeing some very good growth of Jardiance, but we had a pretty important event in Q1 related to the exclusion from CVS. Jardiance do has a very good access, and we basically have seen, post the rebating of the prescriptions of patients, many patients have been switched, we basically have seen resumed growth over the last few weeks. Clearly, the SGLT2 class and Jardiance, in particular, is still a very small part of the overall prescriptions. We estimate that about 30% of patients with diabetes have established cardiovascular disease. So the opportunity for us, is of continued growth, and we're working to accelerate Jardiance and bring Jardiance the catalyst for the growth of the class.

是的。也許只是從構建 Trulicity 季度開始，因為我們還有另一個強勁的季度，持續穩健增長。我們基本上已經看到，新推出的促銷力度加大，基本上對市場加速產生了一些影響，但我們兩者都看到了。我們看到了非常好的市場增長，而且我們基本上看到了在競爭更加激烈的環境中與 Trulicity 的良好股票表現。所以我們非常喜歡我們的職位。我們也有很強的准入地位。最後，有時可能會被低估的東西是我們基本上從醫生和患者本身那裡獲得的患者體驗。我們具有出色的現實世界功效，而且交付非常簡單。所以我們對此感到非常興奮。顯然，REWIND 並沒有改變這一切，但它非常重要，因為我們相信，從長遠來看，我們要在這個類別中具有競爭力，我們將需要心血管結果。由於它與 SGLT2 相關，顯然，我們已經看到 Jardiance 的一些非常好的增長，但我們在第一季度發生了一個非常重要的事件，與 CVS 的排除有關。 Jardiance確實有很好的准入，我們基本上看到，在患者的處方回扣之後，很多患者被轉換，我們在過去幾週基本看到恢復增長。顯然，特別是 SGLT2 類和 Jardiance 仍然只是整個處方的一小部分。我們估計約 30% 的糖尿病患者已確診心血管疾病。所以對我們來說，機會是持續增長，我們正在努力加速 Jardiance 並使 Jardiance 成為班級增長的催化劑。

Great. Thank you, Enrique. Christi?

偉大的。謝謝你，恩里克。克里斯蒂?

Thanks, Geoff for the question. I think you saw yesterday the reinforcement by everyone that the 4-milligram dose is really needed for patients from an efficacy standpoint so our goal is to actually have both doses available. And we'll continue to study both the 2 and the 4 milligrams in other studies that are ongoing.

謝謝，傑夫的問題。我想你昨天看到每個人都強調，從療效的角度來看，患者確實需要 4 毫克的劑量，因此我們的目標是實際提供兩種劑量。我們將繼續在其他正在進行的研究中研究 2 和 4 毫克。

Next, we'll go to the line of Chris Schott with JPMorgan.

接下來，我們將與摩根大通一起前往 Chris Schott。

First one was just on the Humalog performance in the quarter and some of the rebates. So just two questions here. First, can you just quantify what the benefit was in the quarter? And second, can you just elaborate on what's happening with mix here? And can we think about that as sustainable? My second question was on Taltz, channel dynamics, just another question, just quantifying what we saw in terms of the work down this quarter. And you've obviously got some very healthy volume trends, but can you talk a little bit more about the underlying price dynamics in the IL-17s? Are there pressures we should be thinking about beyond just channel work down the quarter that could offset some of that volume growth?

第一個只是關於本季度 Humalog 的表現和一些回扣。所以這裡只有兩個問題。首先，您能否量化本季度的收益？其次，你能詳細說明一下 mix 這裡發生了什麼嗎？我們可以認為這是可持續的嗎？我的第二個問題是關於 Taltz，渠道動態，只是另一個問題，只是量化我們在本季度的工作中看到的內容。而且您顯然已經有了一些非常健康的成交量趨勢，但是您能多談談 IL-17 的潛在價格動態嗎？除了本季度的渠道工作之外，我們是否還應該考慮可能抵消部分銷量增長的壓力？

Chris, thank you for the questions. Just to understand the second question, when you mentioned mix being sustainable, is that specific to Humalog? Or is that more broadly focused across the portfolio of products in the U.S?

克里斯，謝謝你的提問。只是為了理解第二個問題，當您提到混合是可持續的時，這是 Humalog 特有的嗎？還是更廣泛地關注美國的產品組合？

It was actually specifically to Humalog, but if there's a broader trend, would love to hear that as well.

它實際上是專門針對 Humalog 的，但如果有更廣泛的趨勢，我也很想听聽。

Okay, very good. So Trulicity, Enrique, you'll talk about the Humalog in addition to the mix. And then over to Christi for the Taltz channel dynamics. Josh, if you want to make any overarching comments, Enrique, either one on what we're generally seeing in the U.S. across our portfolio for mix. Enrique?

好的，非常好。所以 Trulicity，Enrique，除了混音之外，你還會談論 Humalog。然後轉到克里斯蒂了解 Taltz 頻道動態。喬希，如果你想發表任何總體評論，恩里克，無論是關於我們在美國通常看到的我們的組合產品組合中的任何一個。恩里克?

Very good. So when it comes to Humalog, of course, a strong quarter. We saw about a $50 million benefit in the quarter related to changes in the estimates of rebates and discounts. Part of that was Medicaid and part of that other payer mix changes. We basically see some of those benefits continuing throughout the year. Of course, some of that is also growing as part of Q1, in essence, we are seeing lower Medicaid claims. And basically other dynamics that are slightly favorable when it comes to payer mix, when it comes specifically to Humalog. Now when we look broadly at the portfolio, it is pretty clear that those Medicaid claims is something that we see across the portfolio but not all of our products are as exposed as our insulins are.

很好。因此，當談到 Humalog 時，當然是一個強勁的季度。我們在本季度看到了大約 5000 萬美元的收益，這與回扣和折扣估計的變化有關。其中一部分是醫療補助，另一部分是其他付款人組合的變化。我們基本上看到其中一些好處全年持續。當然，其中一些作為第一季度的一部分也在增長，實質上，我們看到醫療補助索賠減少。基本上，當涉及到付款人組合時，特別是在 Humalog 方面，其他一些稍微有利的動態。現在，當我們廣泛地審視投資組合時，很明顯，這些醫療補助索賠是我們在整個投資組合中看到的東西，但並非我們所有的產品都像我們的胰島素一樣暴露在外。

Great. Thank you, Enrique. Christi?

偉大的。謝謝你，恩里克。克里斯蒂?

Sure. So specifically, the inventory change we saw was about $32 million, quarter 4 and quarter 1. And as we look at the price dynamics and volume growth, ours is volume growth. And as we look to the future, as patients really need the best medications out there, we haven't seen a strong need yet to significantly rebate. I know Novartis' call said that on theirs, but that's not the same case for us.

當然。具體來說，我們看到的庫存變化約為 3200 萬美元，第 4 季度和第 1 季度。當我們查看價格動態和銷量增長時，我們看到的是銷量增長。展望未來，由於患者確實需要最好的藥物，我們還沒有看到大幅回扣的強烈需求。我知道諾華公司的電話是在他們的電話上說的，但對我們來說情況並非如此。

It's the line of Andrew Baum with Citi.

這是安德魯鮑姆與花旗的路線。

A couple of questions, please. Could you indicate your assessment of impact that fit in the doughnut hole in 2019 given that your business of Part B patients. Second, could you talk to your expectations for Alimta post-189 data as well as the stalling of the 340B expansion which I assume would be helpful to you. And then finally, on business development, and oncology, generally, I know that might (inaudible) us back you to go to a competitor. I'm also aware that the deal flow we might have expected from the -- in oncology has not as yet transpired, but could you just update us on your commitment, particularly to immunobiology? And expectations and valuations you see for initial acquisition or for partnering candidates externally.

有幾個問題，請。鑑於您的 B 部分患者業務，您能否說明您對 2019 年適合甜甜圈洞的影響的評估。其次，您能否談談您對 Alimta 189 後數據的期望以及我認為對您有幫助的 340B 擴展的停滯。最後，關於業務發展和腫瘤學，一般來說，我知道我們可能（聽不清）支持你去競爭對手那裡。我也知道，我們可能從腫瘤學中預期的交易流程尚未發生，但您能否向我們介紹您的承諾，特別是對免疫生物學的承諾？以及您對初始收購或外部合作候選人的期望和估值。

Great, Andrew. Thank you for the question. We'll go to Enrique for the first question on the doughnut hole in 2019. And then Sue, if you'd like to comment on expectations for Alimta moving forward as well as per your perspective as the BU President on oncology business development. And either Dave or Josh, you're going to give a corporate perspective, feel free to augment. Enrique?

太好了，安德魯。感謝你的提問。關於 2019 年甜甜圈洞的第一個問題，我們將向 Enrique 提問。然後是 Sue，如果您想評論對 Alimta 前進的期望以及您作為 BU 總裁對腫瘤業務發展的看法。無論是 Dave 還是 Josh，您都將給出一個企業視角，請隨意擴充。恩里克?

So the increased coverage in -- during the doughnut hole for 2019, when we look at our overall portfolio it's about $200 million. Most of it being driven by diabetes.

因此，在 2019 年的甜甜圈洞期間，當我們查看我們的整體投資組合時，覆蓋面的增加約為 2 億美元。其中大部分是由糖尿病驅動的。

Thank you, Enrique. Sue?

謝謝你，恩里克。起訴？

Yes. With regards to Alimta, clearly, we are very pleased with the KEYNOTE-189 data. And as we've mentioned earlier, we have seen growth this quarter on Alimta in the U.S., 8% growth overall, and 3% of that was price, 5% of that was volume. And we've also continued to see increase in huge brands in combination. I think we don't give forecasts on individual products. And I think it's key to note that about 50% of our sales come from the first line and second line, about 40% is first line. With that, we are, as I said, seeing a stabilization in overall share of market and an increasing huge brand. And we continue to see and expect that to increase as we saw some people waiting for the Phase III trial data outcome before starting the combination of the Alimta, Keytruda and combo, so we are really pleased with that. We think that it concerns the benefit that we're seeing with Alimta. Historically, as a standard of care in the first line non-small cell lung cancer setting and we continue to see that, that will be the case going forward. And with regards to our business development, we are continuing to be very interested in BD across all areas including IO. We have talked previously about our CureVac deal which is a bet that we have or one of the betsst that we will be placing with regards to RNA-based vaccines. We anticipate that we will be doing other deals both in the IO space and in other areas in oncology in the future. We are also bringing in new people into our team. Again, we mentioned we were boarding 2 physicians recently. One from Duke and the other from Memorial Sloan Kettering, and you will see us continuing to bring in more external talent.

是的。關於 Alimta，顯然我們對 KEYNOTE-189 數據感到非常滿意。正如我們之前提到的，我們看到本季度美國 Alimta 的增長，總體增長 8%，其中 3% 是價格，5% 是銷量。我們還繼續看到大品牌組合的增加。我認為我們不會對單個產品進行預測。我認為關鍵是要注意，我們大約 50% 的銷售額來自一線和二線，大約 40% 是一線。有了這個，正如我所說，我們看到整體市場份額趨於穩定，品牌越來越大。我們繼續看到並期望這種情況會增加，因為我們看到一些人在開始結合 Alimta、Keytruda 和組合之前等待 III 期試驗數據結果，所以我們對此感到非常高興。我們認為這與我們從 Alimta 看到的好處有關。從歷史上看，作為一線非小細胞肺癌環境中的護理標準，我們繼續看到，這將是未來的情況。關於我們的業務發展，我們繼續對包括 IO 在內的所有領域的 BD 非常感興趣。我們之前曾討論過我們的 CureVac 交易，這是我們對基於 RNA 的疫苗的一個賭注，或者是我們將下注的賭注之一。我們預計未來我們將在 IO 領域和腫瘤學的其他領域進行其他交易。我們還在為我們的團隊引入新人。再次，我們提到我們最近寄宿了 2 名醫生。一個來自杜克大學，另一個來自斯隆凱特琳紀念館，你會看到我們繼續引進更多的外部人才。

Great. Thank you, Sue. Any additional comments on BD?

偉大的。謝謝你，蘇。對 BD 有什麼補充意見嗎？

I would just say we're highly convicted to use our balance sheet to expand our portfolio with BD. We've talked about clinical-stage assets in particular and oncology is the #1 target. So Jeff, I wouldn't read through the relative lack of activity most recently as any sign that would change our conviction. Of course, we need to look at each idea, make sure it makes sense for us to own it, make sure we like the science and valuations are appropriate. But -- so we'd be disciplined on those matters but strategically, we understand we need to be active externally and you can count on us continuing to look at all available choices to add to our pipeline, in particular in oncology.

我只想說，我們非常有罪利用我們的資產負債表來擴大我們與 BD 的投資組合。我們已經特別談到了臨床階段資產，而腫瘤學是第一目標。所以傑夫，我不會把最近相對缺乏活動的情況解讀為任何會改變我們信念的跡象。當然，我們需要審視每一個想法，確保我們擁有它是有意義的，確保我們喜歡科學並且估值是適當的。但是 - 所以我們會在這些問題上受到紀律處分，但從戰略上講，我們知道我們需要在外部保持活躍，您可以指望我們繼續研究所有可用的選擇以添加到我們的管道中，特別是在腫瘤學方面。

Great. Thank you, Dave. And then back to question that John Boris had asked that we did not have the data before, thank you to our Olumiant team for providing that we now have 11,500 patient years of exposure in baricitinib when you add in the post-approval exposures.

偉大的。謝謝你，戴夫。然後回到約翰·鮑里斯（John Boris）問我們之前沒有數據的問題，感謝我們的 Oluminant 團隊提供，當您加上批准後的暴露時，我們現在有 11,500 患者年的巴瑞替尼暴露。

It will be the line of Tony Butler with Guggenheim Securities.

這將是古根海姆證券公司的托尼·巴特勒 (Tony Butler) 的路線。

Two questions, if I may. One is on the pipeline-related, one is galcanezumab. And you do have some data at AAN today, but I'm just curious with respect to the range of somewhat similar products that will come to market as a cluster, I assume, later this year. What makes galca stand out? And can it do so without having a second agent in the bag, be it lasmiditan. And then second, back to the previous question asked on immunobiology, you have had a relationship with an antibody-based company, I assume for bispecifics, and I'm just curious, it seems to be an interesting area with CD 3 engagers and could you speak more to that because it's a way maybe to back in into an area in which you didn't have to go through at least the direct PD-1.

兩個問題，如果可以的話。一個是在管線相關的，一個是galcanezumab。你今天在 AAN 確實有一些數據，但我只是對今年晚些時候將作為一個集群進入市場的一些類似產品的範圍感到好奇。是什麼讓 galca 脫穎而出？它可以在沒有第二個代理的情況下做到這一點，無論是lasmiditan。然後第二個，回到上一個關於免疫生物學的問題，您與一家基於抗體的公司有關係，我假設是雙特異性的，我只是好奇，這似乎是 CD 3 參與者的一個有趣領域，並且可能您對此說得更多，因為這可能是一種回到您不必通過至少直接 PD-1 的區域的方式。

Great. Thank you for the questions, Tony. So Christi, we'll go to you for the galcanezumab and how we intend to succeed in that marketplace. And over to you, Sue, for the question on immunobiology bispecific consumer.

偉大的。謝謝你的問題，托尼。所以克里斯蒂，我們將向您介紹 galcanezumab 以及我們打算如何在該市場取得成功。蘇，關於免疫生物學雙特異性消費者的問題，交給你了。

Sure. So Tony, thanks for the question. I think this is an area where migraine patients haven't had an option for a few decades. And here we are, with a couple of agents coming out quickly together. So first of all, I think it's a really good thing to really have a couple of companies activating these patients. So the first piece is we're going to be better at the consumer-driven area, the direct-to-consumer. And I think our chances there are very good, and we have a history of that. On the data, specifically, we have 50%, 75% and 100% measurements endpoints, and we're the only one that is actually showing a 10% to 15% of the patients have the ability to really be free of migraines totally. The other thing we have is that galca is fast and durable. We see results as early as month 1, and we see the results continue through the 12 months that we've looked at. You were right, we do have the cluster data coming up and nothing has ever worked in this type of migraine, and if we do, it will be a huge win for patients. And obviously, it's then good for differentiating galcanezumab. So our second half launch, we're well prepared for -- to be competitive, and we think we have some differentiation there.

當然。所以托尼，謝謝你的問題。我認為這是偏頭痛患者幾十年來沒有選擇的領域。我們在這裡，有幾個特工很快一起出來。所以首先，我認為真正有幾家公司激活這些患者是一件非常好的事情。所以第一部分是我們將在消費者驅動的領域做得更好，直接面向消費者。我認為我們在那裡的機會非常好，我們有這樣的歷史。具體而言，在數據上，我們有 50%、75% 和 100% 的測量終點，而且我們是唯一一個實際顯示 10% 到 15% 的患者有能力真正完全擺脫偏頭痛的人。我們擁有的另一件事是 galca 快速且耐用。我們早在第 1 個月就看到了結果，而且我們看到結果會持續到我們所研究的 12 個月。你是對的，我們確實有集群數據出現，並且在這種類型的偏頭痛中沒有任何效果，如果我們這樣做，這對患者來說將是一個巨大的勝利。顯然，它有利於區分 galcanezumab。所以我們下半年的發布，我們已經做好了充分的準備——具有競爭力，我們認為我們在那裡有一些差異化。

Great. Thank you, Christi. Sue?

偉大的。謝謝你，克里斯蒂。起訴？

Yes. Tony, thanks for the question on bispecifics here. As we've looked at our IO portfolio and what we want to do, we want to understand really what the next generation of IO agents are. And we've taken 2 bets, I mentioned one, and we'll be taking others, by the way, but 2 that we're taking at the moment. One is it the RNA-based vaccines that we think really could be potentially disruptively in the future. The other is a bispecific. And as you've mentioned, we have ongoing collaborations and actually a number of bispecifics looking at different targets. That should be coming into the clinic very soon, we're excited by those. Another asset that we've got in the clinic that we've talked about before but not too much is the TIM-3, and we are pretty excited by our TIM-3 and think we've got a best-in-class asset there. We've also got an idea. We know that there's some data on ideas, we'll have to see what happens there. But we -- I believe that we've got one that, again, could be differentiated. So those are 2 assets we've got in clinic now. And as you've mentioned, we're taking bets on the RNA-based vaccines and the bispecifics.

是的。托尼，感謝這里關於雙特異性的問題。當我們查看了我們的 IO 產品組合以及我們想要做什麼時，我們想真正了解下一代 IO 代理是什麼。我們已經下注了 2 個，我提到了一個，順便說一下，我們還會下注，但是我們現在下注的是 2 個。一個是我們認為未來可能真正具有破壞性的基於 RNA 的疫苗。另一種是雙特異性的。正如你所提到的，我們正在進行合作，實際上有許多針對不同目標的雙特異性藥物。那應該很快就會進入診所，我們對此感到興奮。 TIM-3 是我們之前在診所中討論過但不多的另一項資產，我們對 TIM-3 感到非常興奮，並認為我們擁有一流的資產那裡。我們也有想法。我們知道有一些關於想法的數據，我們必須看看那裡會發生什麼。但是我們 - 我相信我們已經有了一個可以區分的產品。所以這些是我們現在在診所獲得的兩項資產。正如你所提到的，我們正在押注基於 RNA 的疫苗和雙特異性疫苗。

Thank you, Sue.

謝謝你，蘇。

That's the line of Vamil Divan from Crédit Suisse.

這就是瑞士信貸的 Vamil Divan 的產品線。

So maybe just following up on a couple that were -- topics that were discussed earlier, again, on baricitinib. Kind of coming out of yesterday's discussions, just I know you have a Phase III program in atopic dermatitis. Can you just talk about how you see the sort of risk/reward and the attractiveness of product legacy in atopic dermatitis, where I would think the acceptance of safety concerns maybe a little bit lower? And then the second question I have just following up on the question on the CGRPs. Just curious if you could give your thoughts, given we have BOTOX in the market and also some oral products that generally were used off-label for preventative use. Would you expect that the CGRP antibody's are going to be used in patients that have gone through those products or do you think that there might be an opportunity to be used ahead of either the off-label and/or BOTOX?

所以也許只是跟進一些之前討論過的主題，再次是關於巴瑞替尼。有點像昨天的討論，只是我知道你有一個特應性皮炎的 III 期項目。您能否談談您如何看待特應性皮炎中產品遺留的風險/回報和吸引力，我認為對安全問題的接受度可能會低一些？然後是第二個問題，我剛剛跟進了有關 CGRP 的問題。只是想知道您是否可以提出您的想法，因為我們在市場上有 BOTOX 以及一些通常在標籤外用於預防性使用的口服產品。您是否期望 CGRP 抗體將用於已經使用這些產品的患者，或者您認為可能有機會在標籤外和/或 BOTOX 之前使用？

Great. Vamil, thank you for the questions. So Christi, we'll go to you for both the bari atopic derm question as well as where do you see CGRP is potentially being used.

偉大的。瓦米爾，謝謝你的提問。因此，克里斯蒂，我們將向您諮詢 bari 特應性皮膚問題以及您認為 CGRP 可能在哪裡使用。

Sure. So baricitinib, each disease state has its own benefit/risk ratio. So if you look at what we're studying in our Phase II data with lupus, we have both the 2- and the 4-milligram. If you look at atopic derm, the data that we read out in Phase II, the 2-milligram did work, it just took a little bit longer. So whether it's 2 or 4, we know the patients will get better there. So each disease state really has its own dosing and for rheumatoid arthritis, we strongly believe that 2- and 4-milligram needs to be available in the U.S. as it is and over 40 countries. On the CGRP side, we expect patients to cycle through the generics. And most of them already have. There's like 4 million to 5 million patients that are on preventatives, and then there -- we believe there is a few million more that aren't on preventatives and should be. So we have every expectation that building requirement for the [MWs], for example, the triptans before they go on to a CGRP, but we do expect that we'll compete well versus BOTOX. I mean, getting 21 to 24 injections in your -- around your head for -- doesn't seem as good as having a monthly injection, if I'm a patient. So I think we have an advantage there, and they have their same hurdles from an access standpoint. So I believe that usage will come, and we're already talking to payers about how we make sure that access is available to the patients that need it.

當然。所以巴瑞替尼，每種疾病狀態都有自己的收益/風險比。因此，如果您查看我們在狼瘡的 II 期數據中研究的內容，我們既有 2 毫克，也有 4 毫克。如果你看看特應性皮膚，我們在第二階段讀出的數據，2 毫克確實有效，只是花了一點時間。因此，無論是 2 還是 4，我們都知道患者會在那裡好轉。因此，每種疾病狀態都有自己的劑量，對於類風濕性關節炎，我們堅信美國和 40 多個國家需要提供 2 毫克和 4 毫克的劑量。在 CGRP 方面，我們希望患者能夠循環使用仿製藥。他們中的大多數已經有了。大約有 400 萬到 500 萬患者正在使用預防措施，然後——我們相信還有幾百萬沒有使用預防措施，而且應該使用。因此，我們完全期望 [MW] 的構建要求，例如，曲坦類藥物在進入 CGRP 之前，但我們確實希望我們能與 BOTOX 競爭。我的意思是，如果我是一個病人，在你的頭上進行 21 到 24 次注射似乎不如每月注射一次。所以我認為我們在那裡有優勢，從訪問的角度來看，他們也有同樣的障礙。所以我相信使用會到來，我們已經在與付款人討論我們如何確保需要它的患者可以使用。

Great. Thank you, Christi.

偉大的。謝謝你，克里斯蒂。

And that's the line of Marc Goodman with UBS.

這就是瑞銀的馬克·古德曼 (Marc Goodman) 的觀點。

Just to continue on with the CGRP conversation as well as lasmiditan. Can you just talk about the safety profiles that you see? And how you think these things are going to be all used? I mean, presumably if everything makes it to the market, how the orals will be used, your oral versus CGRP orals? Second question is Taltz. Just can you explain the specialty pharmacy buying pattern issue? And what was the impact on Taltz in the quarter? And there was also some inventory patterns with respect to Forteo, can you quantify that as well?

只是繼續與 CGRP 對話以及 lasmiditan。你能談談你看到的安全概況嗎？您認為這些東西將如何全部使用？我的意思是，大概如果一切都進入市場，口服劑將如何使用，您的口服劑與 CGRP 口服劑？第二個問題是 Taltz。你能解釋一下專業藥房的購買模式問題嗎？本季度對 Taltz 有何影響？還有一些關於 Forteo 的庫存模式，你能量化一下嗎？

Okay. So Dan, if you wouldn't mind talking about some of the safety profiles for a CGRP monoclonal antibody as well as lasmiditan. Christi, if you could then get the second part of that piece of the question that was how we see lasmiditan being used relative to oral CGRPs potentially. And then if you could go over again the Taltz specialty pharmacy buying patterns that we have seen, that affected this quarter's revenues for Taltz.

好的。所以 Dan，如果您不介意談論 CGRP 單克隆抗體和 lasmiditan 的一些安全性概況。克里斯蒂，如果你能得到問題的第二部分，那就是我們如何看待 lasmiditan 相對於口服 CGRP 的潛在使用。然後，如果您可以再次回顧一下我們已經看到的 Taltz 專業藥房購買模式，這會影響本季度 Taltz 的收入。

Great. Thanks. So with respect to the safety profile of galcanezumab, I think, we've really been encouraged by what we've seen in our Phase III trials on safety. I think that's critically important for a preventative for migraine patients could be on for very long time to be well tolerated by the patients and have a very clean safety profile. So that's an important differentiator for galcanezumab and for the class probably of anti-CGRP antibodies. When you get to the orals, which are abortives, the safety profile could be a bit different, and we've seen some evidence of some of that for the oral CGRPs. And I think, Christi, you're going to comment on commercial differentiation.

偉大的。謝謝。因此，關於 galcanezumab 的安全性，我認為，我們在 III 期安全性試驗中看到的情況確實令我們感到鼓舞。我認為這對於偏頭痛患者的預防措施至關重要，因為它可以持續很長時間以被患者很好地耐受並具有非常乾淨的安全性。因此，這是 galcanezumab 和可能的抗 CGRP 抗體類別的一個重要區別。當您使用流產的口服藥物時，安全性可能會有所不同，我們已經看到了口服 CGRP 的一些證據。我認為，克里斯蒂，你會評論商業差異化。

Sure. I think that's one of the big advantages. What we're bringing to marketplace is a platform that we're building for pain. So we have the prevention in galcanezumab, the treatment in lasmiditan, and then we have tanezumab coming. The mechanism of action with lasmiditan is different than the oral CGRPs, and as we look at patients, not everyone responds to the same agent. So we believe that they'll be used similarly for acute phase and that not all patients will respond to one or the other. So obviously our goal would be to win in that marketplace and position ourselves well for that. But we're working on the package to submit later this year.

當然。我認為這是最大的優勢之一。我們為市場帶來的是一個我們為痛苦而構建的平台。所以我們有 galcanezumab 的預防，lasmiditan 的治療，然後我們有 tanezumab。 lasmiditan 的作用機制不同於口服 CGRP，當我們觀察患者時，並不是每個人都對同一種藥物有反應。因此，我們相信它們將類似地用於急性期，並且並非所有患者都會對其中一種有反應。所以很明顯，我們的目標是在那個市場上取勝，並為此做好準備。但我們正在研究今年晚些時候提交的一攬子計劃。

And then on the Forteo question -- oh, I'm sorry, the Taltz specialty pharmacy, I think, I answered that. That was like a $33 million that was the inventory impact for Taltz, but demand was positive quarter-to-quarter. And then on Forteo, the last question on Forteo was basically what we saw was inventory came but in at a different way. We saw the wholesaler buying patterns actually increased volume in Q4 of last year. Some of that has been destocking in Q1 but not all of it. We did have some formulary loss with TYMLOS, the new competitive entries, but that was a really small impact to the overall performance of Forteo.

然後關於 Forteo 的問題——哦，對不起，Taltz 專業藥房，我想，我回答了這個問題。這對 Taltz 的庫存影響相當於 3300 萬美元，但需求環比呈正增長。然後在 Forteo 上，關於 Forteo 的最後一個問題基本上是我們看到的庫存來了，但方式不同。我們看到批發商的採購模式實際上在去年第四季度增加了數量。其中一些已經在第一季度去庫存，但不是全部。我們確實在新的競爭條目 TYMLOS 上出現了一些公式損失，但這對 Forteo 的整體性能影響非常小。

Yes, I was just going to add, I guess, there was a question about using of the CGRP antibodies in refractory patients and just to point out that all of our Phase III pivotal studies had patients who failed on at least 2 other modalities. So that's likely the indication, and I'm not sure that is a big commercial bearing because most patients who've had -- our chronic migrainers or episodic migrainers have tried many other things. So I think the pool of available patients for prevention will be there. The data in our program, I mean, I believe all the competitors is on 2 failures. And despite that, and the data we'll present today, is incredibly strong. A large percent of patients have at least 50% reduction in headache days per month so...

是的，我想補充一下，我想，有一個關於在難治性患者中使用 CGRP 抗體的問題，並且只是要指出，我們所有的 III 期關鍵研究都有至少在 2 種其他方式上失敗的患者。所以這很可能是一個跡象，我不確定這是否具有很大的商業意義，因為大多數患有慢性偏頭痛或發作性偏頭痛的患者都嘗試了許多其他方法。因此，我認為可用於預防的患者庫將在那裡。我們程序中的數據，我的意思是，我相信所有的競爭對手都失敗了 2 次。儘管如此，我們今天將提供的數據非常強大。很大一部分患者每月頭痛天數至少減少 50%，因此...

Thanks, Dave.

謝謝，戴夫。

And that is Dave Risinger with Morgan Stanley.

那就是摩根士丹利的戴夫·瑞辛格。

So I have 2 questions. First, just a follow-up on the CGRPs. There was a Reuters article today that described how Express Scripts is asking for lower list prices on CGRPs. Could you just provide a comment on that? And whether a manufacturer could trust PBMs to not extract significant rebates in the event that a manufacturer does list the list price lower than expected? And then second, with respect to Trulicity REWIND, the slide that you published this morning indicates an internal readout in 2018 but not an external readout. And I just wanted to understand that a little bit better because clinicaltrials.gov indicates July completion of that trial.

所以我有2個問題。首先，只是對 CGRP 的跟進。今天有一篇路透社文章描述了 Express Scripts 如何要求降低 CGRP 的標價。你能就此發表評論嗎？如果製造商列出的標價低於預期，製造商是否可以相信 PBM 不會獲得大量回扣？其次，關於 Trulicity REWIND，您今天早上發布的幻燈片顯示了 2018 年的內部讀數，而不是外部讀數。我只是想更好地理解這一點，因為臨床試驗.gov 表明該試驗在 7 月完成。

Great. Thank you, Dave. While the article that you were referencing was specific to CGRPs, your question's really more of a policy question. So Dave, if you would mind taking the first part of Dave Risinger's question. Then Enrique, over to you for the Trulicity REWIND, timing of internal readout and top line press release relative to presentation of the medical meeting.

偉大的。謝謝你，戴夫。雖然您引用的文章是針對 CGRP 的，但您的問題實際上更像是一個政策問題。所以戴夫，如果你介意回答戴夫·瑞辛格問題的第一部分。然後，Enrique 交給你關於 Trulicity REWIND、內部讀數的時間安排和與醫療會議介紹相關的頂線新聞稿。

Yes. Thanks, Dave. Yes, I did glance at that interview with Steve Miller this morning. I was really happy to see that Express Scripts is now for value-based pricing. Of course, we've been for this kind of construct for years because we believe in the performance of our products, and I think in the case of migraine drugs and many other drugs, diabetes, other autoimmune drugs, even in oncology, I think, if you're willing to enter into these discussions. The point about lower list price is a little bit moot. I think the idea that the price varies in a value-based scheme based on actual product performance, I think that's the key piece. So the value determination we will need to do, it's difficult to comment specifically on launch products. Would we trust the PBMs? Well, I think we work closely with all the major payers in the U.S. I'm happy to see that ESI is now changing their view and support of this kind of construct. We'll be happy to work with them on it.

是的。謝謝，戴夫。是的，我確實看過今天早上對史蒂夫米勒的採訪。我很高興看到 Express Scripts 現在提供基於價值的定價。當然，我們多年來一直支持這種結構，因為我們相信我們產品的性能，我認為對於偏頭痛藥物和許多其他藥物、糖尿病、其他自身免疫藥物，甚至在腫瘤學中，我認為，如果您願意參與這些討論。關於降低標價的觀點有點沒有實際意義。我認為價格在基於實際產品性能的基於價值的方案中變化的想法，我認為這是關鍵部分。所以我們需要做的價值確定，很難具體評論發布產品。我們會相信 PBM 嗎？好吧，我認為我們與美國所有主要付款人密切合作。我很高興看到 ESI 現在正在改變他們對這種結構的看法和支持。我們很樂意與他們合作。

Thanks, Dave. Enrique?

謝謝，戴夫。恩里克?

So when it comes to REWIND, we do expect internal readout in the second half with the top line press release likely in early Q4. And we will be targeting the full disclosure of the results at the next year's ADA meeting.

因此，當談到 REWIND 時，我們確實預計下半年會有內部讀數，頂線新聞稿可能會在第四季度初發布。我們的目標是在明年的 ADA 會議上全面披露結果。

And Dave, just to be clear, the ct.gov date on the site is the expectation for the last event. Obviously, with it being event-driven, there is uncertainty around that. We will -- once we have the last event occur, that would trigger then the analysis to be done. It does take a number of months to go ahead and get all that final visits and data into the system, clean and validate the database and then run our tables, figures and listings and report out.

戴夫，為了清楚起見，網站上的 ct.gov 日期是對最後一次活動的預期。顯然，由於它是事件驅動的，因此存在不確定性。我們將 - 一旦我們發生最後一個事件，這將觸發然後進行分析。確實需要幾個月的時間才能將所有最終訪問和數據輸入系統，清理和驗證數據庫，然後運行我們的表格、數字和列表並進行報告。

It's the line of Jami Rubin with Goldman Sachs.

這是 Jami Rubin 與 Goldman Sachs 的路線。

Maybe for you, David and Christi. I don't want to put words in your mouth, but it sure sounds like you're not going to launch baricitinib unless you can get both 2- and 4-milligrams approved, is that correct? And can you cite specific examples where the FDA goes against the panel recommendation? I know recently, there was a Pasara drug that was approved even though the panel went against it, but that was a non-opioid drug, and in this case, there is another drug from the market. So I'm just wondering if you can comment on your level of confidence that you could convince the FDA to vote against the FDA panel on the 4-milligram tablet? And if you can't, would it be your decision not to launch baricitinib for RA? And to what extent would that affect your 5% top line growth objective?

也許對你來說，大衛和克里斯蒂。我不想把話放在你的嘴裡，但聽起來你肯定不會推出巴瑞替尼，除非你能同時獲得 2 和 4 毫克的批准，對嗎？你能舉出 FDA 反對專家組建議的具體例子嗎？我知道最近有一種 Pasara 藥物被批准，儘管專家組反對它，但那是一種非阿片類藥物，在這種情況下，市場上還有另一種藥物。所以我只是想知道你是否可以評論你的信心水平，你可以說服 FDA 投票反對 FDA 小組的 4 毫克片劑？如果你不能，你會決定不為 RA 推出巴瑞替尼嗎？這會在多大程度上影響您 5% 的收入增長目標？

Great. Christi, do you want to go ahead and answer the question related to the launch, 2 and 4, et cetera. And then maybe Josh, if you want to comment on expectations versus 2020.

偉大的。克里斯蒂，你想繼續回答與發射、2 和 4 等相關的問題嗎？如果你想對 2020 年的預期發表評論，也許還有 Josh。

Sure. As I said before, I think the promising thing we saw is that there was unanimity in terms of the 4-milligram efficacy. And so the thing that you saw on the voting was based on a specific indication. And as we continue to work with the FDA on our labeling and our path to the market, that's where we can say, we're at the highest unmet need so that the patients who are suffering so much in the United States have access as they do in 40 other countries to improve their pain and improve their lives. So we will continue to talk to them about what is the path for both 2- and 4-milligrams, and what is the indication that we can best serve the highest unmet need population. So I think one of the things you saw on the vote was the wording was very specific to the indication that was presented, which was after methotrexate. And then the AdCom, so I can't comment or recall of the any AdComs in terms of overruling, but I think, as I said, it wouldn't be overruling the AdCom if we look at a different and carve-out indication for 4-milligrams that benefits patients the most and make 2-milligram available as well to lower risk patients.

當然。正如我之前所說，我認為我們看到的有希望的事情是在 4 毫克的功效方面達成了一致。因此，您在投票中看到的內容是基於特定的指示。隨著我們繼續與 FDA 就我們的標籤和進入市場的道路合作，我們可以說，我們處於最高的未滿足需求，以便在美國遭受如此多痛苦的患者能夠獲得在其他 40 個國家做，以減輕他們的痛苦並改善他們的生活。因此，我們將繼續與他們討論 2 和 4 毫克的途徑是什麼，以及我們可以最好地服務於最高未滿足需求人群的跡象。所以我認為你在投票中看到的一件事是措辭非常具體到所提出的指示，即甲氨蝶呤之後。然後是 AdCom，所以我無法評論或回憶任何 AdCom 的否決，但我認為，正如我所說，如果我們看一個不同的和排除的跡象，它不會推翻 AdCom 4 毫克對患者最有益，並使 2 毫克也可用於低風險患者。

Thank you, Christi. Josh?

謝謝你，克里斯蒂。喬什？

Thank you, Jamie. I think we've been clear about our growth expectations through 2020, which is a 5% compound annual growth rate, and the 5% is the minimum and not dependent on any single product. We're confident in our growth prospect. I think if you look at where we are in Q1, we're ahead of our targets to get to a 5% growth in 2020. The strength of the new products that we have on the market today and the potential new launches in team and other things that we've talked about already, I think, give us good confidence that we'll be there in 2020. We're still excited about the prospects of Olumiant, particularly outside the U.S. where we have already launched. But I think just looking at analyst models, the dollars associated with the U.S. sales of Olumiant in 2020, I think, in most of your models, are pretty small anyway. But we're confident in the strength of the portfolio, and the new products will continue to drive our growth at more -- that 5% minimum is still valid.

謝謝你，傑米。我認為我們已經明確了到 2020 年的增長預期，即 5% 的複合年增長率，5% 是最低的，不依賴於任何單一產品。我們對我們的增長前景充滿信心。我認為，如果您看看我們在第一季度的情況，我們已經超額完成了 2020 年實現 5% 增長的目標。我們今天在市場上擁有的新產品的實力以及團隊中潛在的新產品發布和我認為，我們已經討論過的其他事情讓我們充滿信心，我們將在 2020 年到達那裡。我們仍然對 Olumiant 的前景感到興奮，特別是在我們已經推出的美國以外的地方。但我認為，僅看分析師模型，與 2020 年 Olumiant 在美國的銷售額相關的美元，我認為，在你們的大多數模型中，無論如何都相當小。但我們對產品組合的實力充滿信心，新產品將繼續推動我們的增長——最低 5% 仍然有效。

Great. Thanks, Josh.

偉大的。謝謝，喬希。

It's the line of Steve Scala with Cowen.

這是史蒂夫·斯卡拉（Steve Scala）和考恩（Cowen）的台詞。

A couple of questions. First on REWIND, there's some concern about the less sick population being studied versus some of your competitors' study. Can you talk about how you design REWIND to still achieve its endpoint despite a population possibly generating fewer events? So maybe you can comment on how you arrived at the trial size, duration and also the statistical power. And then secondly, a couple of questions on Elanco. Yesterday, it was announced that you hired a CFO for Elanco. Is this a newly created position? And why was it done now? And can you comment on poultry trends. I think you commented -- no, can you comment on swine and cattle? You've already commented on poultry.

幾個問題。首先在 REWIND 上，與一些競爭對手的研究相比，人們對正在研究的患病人群較少存在一些擔憂。您能否談談您如何設計 REWIND 以在人口可能產生較少事件的情況下仍能實現其終點？因此，也許您可以評論您是如何得出試驗規模、持續時間以及統計功效的。其次，關於 Elanco 的幾個問題。昨天，宣布您為 Elanco 聘請了一名首席財務官。這是一個新創建的職位嗎？為什麼現在才完成？你能評論家禽趨勢嗎？我想你評論了——不，你能評論豬和牛嗎？你已經評論過家禽。

Great. Steve, thank you for the question. So we're going around the horn here. Enrique, if you'll take the first question on the design of REWIND. Josh, the Elanco CFO hiring that was announced yesterday. And then Jeff, if you can give some more details on other parts of portfolio, including swine that we didn't comment on in the prepared remarks. Enrique?

偉大的。史蒂夫，謝謝你的問題。所以我們在這裡繞著喇叭走。恩里克，如果你願意回答第一個關於 REWIND 設計的問題。昨天宣布的 Elanco 首席財務官招聘喬希。然後傑夫，如果你能提供更多關於投資組合其他部分的細節，包括我們在準備好的評論中沒有評論的豬。恩里克?

Well, REWIND is an event-driven trial. So we will basically have the close-out of this trial when we hit the certain number of events. And the trial is appropriately powered for us to show basically a statistical difference, if the product were to show it, that is meaningful. So we are pretty confident. I do know that we've gotten a lot of questions about the population that we have enrolled and whether that population is maybe less sick. We, at this point in time, I think, we basically want to see the outcomes of the trial. We do have a lot of expertise when it comes to designing cardiovascular trials, and we're confident that we've designed this trial in the appropriate way. Dan, I don't know if you want to make any other comments.

嗯，REWIND 是一個事件驅動的試驗。所以當我們達到一定數量的事件時，我們基本上會結束這次試驗。並且該試驗為我們提供了適當的動力，基本上可以顯示統計差異，如果產品要顯示它，那是有意義的。所以我們很有信心。我確實知道，我們已經收到了很多關於我們註冊的人口的問題，以及這些人口的病情是否可能不那麼好。我們，在這個時間點，我認為，我們基本上希望看到試驗的結果。在設計心血管試驗方面，我們確實擁有很多專業知識，我們相信我們以適當的方式設計了這項試驗。丹，我不知道你是否想發表任何其他意見。

No, that was correct. I would just add that we'll have one of the longer-duration trials here in terms of the follow-up time on these patients, which gives us sort of more area under the curb, time for the drug to work and have its effect on cardiovascular outcomes. So although the lower-end band rate mandate a larger and longer trial, the increased duration actually we see as a benefit to showing an effect.

不，那是正確的。我只想補充一點，就這些患者的隨訪時間而言，我們將在這裡進行一項持續時間較長的試驗，這為我們提供了更多的限制區域，讓藥物有時間發揮作用並發揮作用關於心血管結局。因此，儘管較低端的頻帶率要求進行更大和更長的試驗，但實際上我們認為增加的持續時間是顯示效果的好處。

Thank you, Dan. Josh?

謝謝你，丹。喬什？

Steve, our -- first, our strategic evaluation of Elanco is continuing as planned, and we'll be in a position in our Q2 earnings call to announce our strategic direction. Our hiring of Chris Jensen as the CFO for Elanco adds to that analysis he brings with external experience and I think will position us well for any future direction that we announce and look to execute after our Q2 earnings call.

史蒂夫，我們——首先，我們對 Elanco 的戰略評估正在按計劃進行，我們將在第二季度財報電話會議上宣布我們的戰略方向。我們聘請 Chris Jensen 擔任 Elanco 的首席財務官，增加了他通過外部經驗帶來的分析，我認為這將為我們在第二季度財報電話會議後宣布並希望執行的任何未來方向做好準備。

Great. Thanks, Josh. Over to you, Jeff.

偉大的。謝謝，喬希。交給你了，傑夫。

Yes. Steve, so first it's from the industry perspective, at a high-level, beef continues to be stable and continue to grow. Dairy is a slower recovery, expected probably as an industry later in '19. And swine, I think the eyes are a little bit on trade but again, pretty stable overall. So we feel pretty good about the overall industry economics. No material impact on us. I think everyone's -- as Josh said in his comments, we're going to continue to watch trade. I don't think it's relative to a feed additive issue or anything like that. It would be much more just about the impact that trade barriers could have on the overall economics, especially of the U.S. industry. At this time, we don't see anything and definitely no impact on us. As you look at Elanco's business, food animal will return to growth in the second half as we've stated. We see that led heavily by poultry and swine, less so by ruminants.

是的。史蒂夫，所以首先從行業的角度來看，在高水平上，牛肉繼續保持穩定並繼續增長。乳製品是一個較慢的複蘇，預計可能會在 19 年晚些時候成為一個行業。豬，我認為眼睛有點關注貿易，但總體來說還是相當穩定的。所以我們對整個行業的經濟狀況感覺很好。對我們沒有實質性影響。我認為每個人都 - 正如喬什在他的評論中所說，我們將繼續關注交易。我認為這與飼料添加劑問題或類似問題無關。更多的只是貿易壁壘可能對整體經濟產生的影響，尤其是對美國工業的影響。此時，我們什麼都看不到，也絕對不會對我們產生影響。正如我們所說，當您查看 Elanco 的業務時，食用動物將在下半年恢復增長。我們看到家禽和豬在很大程度上導致了這種情況，反芻動物則較少。

Great. Thanks, Josh.

偉大的。謝謝，喬希。

Next is the of line Umer Raffat from Evercore.

接下來是來自 Evercore 的 Umer Raffat。

On Trulicity, I noticed into the Phase III investigating a really high dose, 4.5 milligrams in diabetes, and I was just curious, a, what your thought process is but also your expectations in weight loss in that trial? And I would've thought that at such a high dose, you might have included a semaglutide comparator as well. So just curious how you thought about that trial. And then -- and a quick follow-up on animal health. Is Posilac and Optaflexx still the driver that's been weighing in? I just wanted to understand the market access pressures in (inaudible).

在 Trulicity 上，我注意到在第三階段研究了一個非常高的劑量，4.5 毫克的糖尿病，我只是好奇，a，你的思維過程是什麼，以及你對該試驗減肥的期望？而且我會認為，在如此高的劑量下，您可能還包括了一個 semaglutide 比較器。所以只是好奇你是如何看待那次試驗的。然後 - 以及對動物健康的快速跟進。 Posilac 和 Optaflexx 仍然是一直在權衡的驅動因素嗎？我只是想了解（聽不清）的市場准入壓力。

Umer, thank you for the question. So Enrique, on the recently initiated study for Trulicity using some higher doses. And then Jeff, back to you for some of the animal health dynamics with Posilac and Optaflexx.

烏默爾，謝謝你的提問。因此，Enrique 在最近啟動的 Trulicity 研究中使用了一些更高的劑量。然後 Jeff，回到你身邊，了解 Posilac 和 Optaflexx 的一些動物健康動態。

So we are studying both 3- and 4.5-milligrams. We believe those doses can be well-tolerated if appropriately titrated. And we basically have designed this trial in a way that it can show actually a difference, from a regulatory perspective, vis-à-vis dula 1.5 when it comes to hemoglobin A1c. We are also expecting to see important difference when it comes to weight loss, but recently that we made the A1c endpoint from a risk/benefit perspective in order to get this product approved.

所以我們正在研究 3 和 4.5 毫克。我們相信，如果適當滴定，這些劑量可以很好地耐受。我們基本上設計了這個試驗，從監管的角度來看，它實際上可以顯示出與 dula 1.5 在血紅蛋白 A1c 方面的差異。我們也期望在減肥方面看到重要的差異，但最近我們從風險/收益的角度製定了 A1c 終點，以使該產品獲得批准。

Thank you, Enrique. Jeff?

謝謝你，恩里克。傑夫?

Yes. So market access issues continue to be definitely an area that we're focused on, and again, we have taken proactive actions, as Josh mentioned, with the strategic exiting as we're assessing our decisions here with Posilac and then exiting the business. But headwinds do continue for Posilac. I would note on our food animal business, first of all, international grew, as you'll note in the backup slides that we saw, close to 2% growth in OUS food animal. The net 10%, though, I would highlight, came from, one, the majority of that being Posilac and the declining use, and again, that's driven by our exits and then some U.S. buying patterns relative to Q1 of 2017. On ractopamine, competition continues, although, we're continuing to see our business hold and remain stable in this area.

是的。因此，市場准入問題仍然絕對是我們關注的一個領域，正如喬希所說，我們再次採取了積極行動，在我們評估我們與 Posilac 的決定然後退出業務時，戰略性退出。但波西拉克的逆風確實繼續存在。我會注意到我們的食用動物業務，首先，國際增長，正如您在我們看到的備用幻燈片中所看到的那樣，OUS 食用動物的增長率接近 2%。不過，我要強調，淨 10% 來自一個，其中大部分是 Posilac 和使用量的下降，這也是由我們的退出驅動，然後是相對於 2017 年第一季度的一些美國購買模式。關於萊克多巴胺，競爭仍在繼續，儘管我們繼續看到我們的業務在該領域保持穩定。

Great. Thank you, Jeff.

偉大的。謝謝你，傑夫。

It's the line of Jason Gerberry with Bank of America.

這是 Jason Gerberry 與美國銀行的產品線。

First question is just on Verzenio. Feedback from Pfizer is that, at least in the U.S., the metastatic market for the CDK4/6 agents is getting increasingly well-penetrated, and that maybe more of the near- to medium-term growth that is shifting to x U.S. expansion, at least until label expansion occurs with more early use in breast cancer setting. So I'm just kind of curious if you agree with that assessment. And as we look at Verzenio, the real growth opportunity in the U.S. is going to be contingent upon getting new patients start share versus your competitors. And then just the second question on CGRP front, how important do you think early mover advantage is in this category? One of the 3 kind of more advanced players in the market faces some uncertainty into its June PDUFA date. So just kind of curious how important you think early mover advantage would be in the category.

第一個問題是關於 Verzenio。輝瑞的反饋是，至少在美國，CDK4/6 藥物的轉移性市場滲透率越來越高，而且可能更多的中短期增長正在轉向 x 美國擴張，在至少直到標籤擴展發生在乳腺癌環境中更早期的使用。所以我很好奇你是否同意這個評估。當我們審視 Verzenio 時，美國真正的增長機會將取決於讓新患者開始分享與競爭對手相比的份額。然後是關於 CGRP 方面的第二個問題，您認為先行者優勢在這一類別中有多重要？市場上三種更先進的參與者之一在其 6 月 PDUFA 日期面臨一些不確定性。所以有點好奇，你認為先發優勢在該類別中的重要性。

Jason, thank you for the question. So Sue, we'll go to you for the Verzenio question. And then Christi, over to you for the question on the CGRP first mover advantage.

傑森，謝謝你的問題。所以 Sue，我們會去找你回答 Verzenio 的問題。然後克里斯蒂，請您回答有關 CGRP 先發優勢的問題。

Yes, thanks for the question on Verzenio. With regards to -- well, firstly, we're very pleased with the uptake. I think Josh mentioned, we've got our 15% new to branch share. And when we launched it, we launched with the single agent activity and the combination with fulvestrant, which is about 1/3 of the market. Literally just the end of the February, we launched with the larger indication which is the aromatase inhibitor, it's 2/3 of the market, and we are now at 15% in new to brand. We feel good about that. With regards to the actual market, we see plenty of opportunity actually for both growth in the market and also taking share. With regards to growth, about 50% of patients are treated with the CDK 4 and 6 inhibitors. So again, we see an opportunity there. One of the things that we're trying to do is to ensure that physicians really understand patients that can benefit the most, and we presented data on patients with concerning clinical characteristics where with Verzenio, we were able to see that even in those patients, we could see robust efficacy similar to the overall patient population. Obviously, with the data that we've got in with the aromatase inhibitor as well, the 28.2 month PFS is seen as robust as well. We see that as beneficial. We also see that we've got a differentiated molecule with single agent activity in continuous dosing. So our belief is that we can both compete within the market and that there still continues to be opportunity for growth in the -- for the overall CDK market in the U.S., and of course, OUS. We have submitted to Europe and Japan, and we'd hope to get approval later this year in both those geographies.

是的，感謝關於 Verzenio 的問題。關於 - 嗯，首先，我們對吸收非常滿意。我想 Josh 提到過，我們有 15% 的新分公司份額。而在我們推出的時候，我們以單一的代理活動和與氟維司群的組合推出，約佔市場的1/3。從字面上看，就在 2 月底，我們推出了更大的適應症，即芳香酶抑製劑，它佔市場的 2/3，現在我們的新品牌佔 15%。我們對此感覺良好。關於實際市場，我們實際上看到了市場增長和份額的大量機會。關於生長，大約 50% 的患者接受 CDK 4 和 6 抑製劑治療。因此，我們再次看到了機會。我們正在嘗試做的一件事是確保醫生真正了解最能受益的患者，我們提供了具有相關臨床特徵的患者數據，在 Verzenio 中，我們能夠看到即使在這些患者中，我們可以看到與整體患者群體相似的強大療效。顯然，根據我們獲得的芳香酶抑製劑數據，28.2 個月的 PFS 也被認為是穩健的。我們認為這是有益的。我們還看到，我們在連續給藥中獲得了具有單一藥劑活性的分化分子。因此，我們的信念是，我們都可以在市場上競爭，而且美國的整個 CDK 市場，當然還有 OUS，仍有繼續增長的機會。我們已經向歐洲和日本提交了申請，我們希望在今年晚些時候在這兩個地區獲得批准。

Great. Thank you, Sue. Christi?

偉大的。謝謝你，蘇。克里斯蒂?

So on how important CGRP and early mover is. If you look at different classes, it depends on the differentiation strategy piece. In general, though, 3 to 4 months is not a big deal. I mean, by the time you get your label and get approved, and you're talking about access, really, it's not a big difference. If you're looking at a bigger delay, and you have 2 agents in the marketplace, and you're 12 to 18 months later, that is a detriment for sure.

那麼關於CGRP和先行者的重要性。如果您查看不同的類別，則取決於差異化策略。不過，一般來說，3 到 4 個月並不是什麼大問題。我的意思是，當您獲得標籤並獲得批准時，您正在談論訪問權限，實際上，這並沒有太大區別。如果您正在考慮更大的延遲，並且您在市場上有 2 個代理，而您在 12 到 18 個月之後，那肯定是不利的。

Thank you, Christi.

謝謝你，克里斯蒂。

Next is from the line of Alex Arfaei with BMO Capital Markets.

接下來是來自 BMO Capital Markets 的 Alex Arfaei。

This is (inaudible) for Alex Arfaei. I just had one question. Could you provide additional thoughts behind your decision to discontinue the BACE inhibitor on its own? And yet advance the combination with the N3pG antibody? And what was the milestone achieved to drive this decision?

這是（聽不清）Alex Arfaei。我只有一個問題。您能否提供更多關於您決定自行停用 BACE 抑製劑的想法？還推進與 N3pG 抗體的組合？推動這一決定的里程碑是什麼？

Great. Thank you for the question. Dan, if you'd like to comment.

偉大的。感謝你的提問。丹，如果你想發表評論。

Yes, thanks for that question. So you're correct that we terminated the monotherapy for our Phase II BACE inhibitor. That was based on a combination of external data readouts, which, of course, you're familiar with as well as our internal look at the data. Our theory behind this compound initially was that given its higher brain penetration, this would have a favorable -- more favorable safety profile. However, we also sought to demonstrate efficacy in Phase II. And that was -- futility for efficacy was what drove us towards stopping it. Now the rationale to continue it in -- and of course, in monotherapy, our bet continues to be on amino-based statin Phase III for monotherapy. As you commented, we continue with the combination. Here, I think we have a growing understanding that we need to clear the Abeta out of the brain with the plot clearing antibody, in this case, N3pG and also inhibit its production. So hitting it from both ends is the rationale there for the combo.

是的，謝謝這個問題。所以你說得對，我們終止了 II 期 BACE 抑製劑的單一療法。這是基於外部數據讀數的組合，當然，您熟悉這些讀數以及我們對數據的內部觀察。我們最初支持這種化合物的理論是，鑑於其更高的大腦滲透性，這將具有有利的——更有利的安全性。然而，我們也試圖證明在 II 期的療效。那就是 - 功效無效是驅使我們停止它的原因。現在繼續它的基本原理——當然，在單一療法中，我們的賭注仍然是基於氨基的他汀類藥物 III 期單一療法。正如您評論的那樣，我們繼續組合。在這裡，我認為我們越來越了解我們需要用情節清除抗體清除大腦中的 Abeta，在這種情況下，N3pG 並抑制其產生。因此，從兩端擊中它是組合的基本原理。

Thank you, Dan.

謝謝你，丹。

It's the line of David Maris with Wells Fargo.

這是 David Maris 與 Wells Fargo 的產品線。

I have a couple of questions. First, going back on the administration's potential moves. When you mentioned the passthrough pricing net of rebates, can you address, that assumes that -- or does it assume that PBMs will willingly just make less money? Or how do you think mechanistically that will work without having an impact to PBMs? And then separately, if you could just provide us with -- if you are going to think of your top 10 or 20 products relative pricing average in the U.S. versus, say, developed Europe, what would you say the differential in net pricing would be? Is it as large as some people think? Or is it because of all the discounts that it's much smaller?

我有一些問題。首先，回顧政府的潛在舉措。當您提到扣除回扣的直通定價時，您能否解決這個假設——或者它是否假設 PBM 願意只賺更少的錢？或者您認為如何在不影響 PBM 的情況下機械地工作？然後單獨地，如果您可以向我們提供 - 如果您要考慮您的前 10 或 20 種產品在美國的相對定價平均值與例如歐洲發達地區，您會說淨定價的差異是多少?有一些人想像的那麼大嗎？或者是因為所有的折扣，它要小得多？

Great. David, thank you for the questions. Dave Ricks, we'll have you take both those.

偉大的。大衛，謝謝你的提問。戴夫·里克斯，我們會讓你把這兩個都拿走。

Sure. Thanks, David. So just on the rebate passthrough, as it relates to the Part D program, we have done modeling ourselves as well as pharma and I know that TMAS has as well. The idea isn't free as you point out, but as Scott Gottlieb has been saying on his podium speeches lately, we've somehow devised a system where the sick subsidize the well. And I think there's something ethically wrong with that. I think there's a growing consensus about that even amongst PBMs, apparently. So the idea would be that premiums would modestly grow across the Part D program. We're talking $1 or $2 per member per month was -- is probably all that's necessary, in exchange for passing some through portion, not 100%, but some portion of rebates to consumers in the Part D program, in particular, when they're exposed to the doughnut hole and beyond that, their share of the catastrophic side. So that's the basic idea. In that model, I think Part D plan providers would just be making a trade-off, which are despite the higher premiums, in exchange for a rebate passthrough. And of course, that math requires some assumptions about how much rebates pass through. Our position is that it needs to be well more than half both through reducing competitive middleman and manufacturers to raise list prices, which I think is a positive objective here as well as to meaningful out-of-pocket savings at the point of sale. In commercial plans, the dynamics are a little bit different. But here, I think the ultimate decider will be the ultimate payers, which are commercial payers like our company and other Fortune 500 companies. I think that they are the market makers, not the PBMs. I think if they decide that employees would like to have rebate passthrough in their plans as a matter of competition for labor, that's what will happen. And Lilly's made that choice, for instance, already and the PBM we use is implementing it.

當然。謝謝，大衛。因此，僅在與 D 部分計劃相關的回扣傳遞中，我們已經完成了自己和製藥公司的建模，我知道 TMAS 也有。正如你所指出的，這個想法並不是免費的，但正如斯科特·戈特利布最近在他的講台上所說的那樣，我們以某種方式設計了一個病人補貼井的系統。我認為這在道德上是有問題的。我認為，顯然，即使在 PBM 中，對此也有越來越多的共識。因此，我們的想法是保費將在 D 部分計劃中適度增長。我們所說的每位會員每月 1 美元或 2 美元可能是所有必要的，以換取在 D 部分計劃中將一些通過部分，而不是 100%，而是部分回扣給消費者，特別是當他們'暴露在甜甜圈洞中，除此之外，他們在災難性方面的份額。這就是基本的想法。在這種模式下，我認為 D 部分計劃提供者只是在進行權衡，儘管保費較高，以換取回扣傳遞。當然，這個數學需要一些關於通過多少回扣的假設。我們的立場是，通過減少有競爭力的中間商和製造商來提高標價，需要超過一半，我認為這是一個積極的目標，也是在銷售點實現有意義的自付費用節省。在商業計劃中，動態略有不同。但在這裡，我認為最終的決定者將是最終的支付者，他們是像我們公司和其他財富 500 強公司這樣的商業支付者。我認為他們是做市商，而不是 PBM。我認為如果他們決定員工希望在他們的計劃中通過回扣作為勞動力競爭的問題，那就會發生這種情況。例如，禮來公司已經做出了這樣的選擇，而我們使用的 PBM 正在實施它。

As -- the second question was the European pricing. And I think if you look at big markets like China, Japan and Germany and then compare that to government pricing in the U.S., a blend of Medicaid, DOD, BBA and Part D, I think most policymakers would be surprised to find that the U.S. government pricing is really not that different across commonly used medications from those major markets. If you change the market basket to include share single-payer models at particularly market hits where they have a lot of layers of approval which have the effect of beating down manufacture pricing or use long delay periods, which erode IP, et cetera. It's less of a fair competition, but I mentioned China, Japan, Germany did, the next 3 biggest markets but also, a relatively rapid market introduction post the regulatory approval. And I think those are important apples-to-apples comparisons. That kind of analysis, I think, you should expect the pharma group to do more of as we continue through this regulatory phase of price reform. I think it will shed a favorable light on the kind of deals "that the U.S. government gets today".

作為 - 第二個問題是歐洲定價。我認為，如果你看看像中國、日本和德國這樣的大市場，然後將其與美國的政府定價進行比較，混合了 Medicaid、DOD、BBA 和 D 部分，我認為大多數決策者會驚訝地發現美國與這些主要市場的常用藥物相比，政府定價實際上並沒有太大差異。如果您將市場籃子更改為在特別受歡迎的市場中包括共享單一付款人模型，在這些模型中，它們具有許多層級的批准，這會降低製造商的定價或使用較長的延遲期，從而侵蝕知識產權等。這不是一個公平的競爭，但我提到了中國、日本、德國，這是接下來的 3 個最大市場，而且在監管部門批准後市場引入相對較快。我認為這些是重要的蘋果對蘋果的比較。這種分析，我認為，隨著我們繼續通過價格改革的監管階段，你應該期望製藥集團做更多的事情。我認為這將為“美國政府今天獲得的”交易提供有利的啟示。

Thanks, Dave.

謝謝，戴夫。

And that is the line of Steve Scala with Cowen.

這就是 Steve Scala 和 Cowen 的台詞。

A couple of questions. It was mentioned that you have seen lower Medicaid utilization, but I'm not clear on why you have seen that. So maybe you can amplify. And then secondly, the abemaciclib pancreatic Phase II study that was stopped, that trial was not to have read out till late 2018 or early 2019. So was it stopped for futility at an interim look, for instance? And does this failure in pancreatic decrease your interest in other new tumor types?

幾個問題。有人提到您看到醫療補助使用率較低，但我不清楚您為什麼會看到這種情況。所以也許你可以放大。其次，已停止的 abemaciclib 胰腺 II 期研究，該試驗要到 2018 年底或 2019 年初才能宣讀。那麼，例如，它是因為臨時看起來徒勞而停止了嗎？胰腺的這種失敗是否會降低你對其他新腫瘤類型的興趣？

Thank you for the question. Enrique, if you'd like to comment on the first question on the lower-than-expected Medicaid utilization. And then over to you, Sue, on the pancreatic cancer trial.

感謝你的提問。恩里克，如果您想對第一個關於低於預期的醫療補助使用率的問題發表評論。然後交給你，蘇，關於胰腺癌試驗。

So we make our accruals for rebates and discounts before we actually receive the claims. In the case of Medicaid, it tends to lack significantly more, some of those -- the receipts of those claims significantly more than in commercial plans and other plans. So what -- we basically have our estimates, and what we basically have seen is that the claims that we have received have been lower than we had expected. So that's -- now there could be a number of reasons for that, but at this point in time, we are basically thinking as well, okay, as we are not only looking at the past, but what does this mean for us is we are looking at our accruals for Q1 and for the rest of the year and the reason why we have a benefit coming from Medicaid when we look at the entire year.

因此，我們在實際收到索賠之前就應計回扣和折扣。就醫療補助而言，它往往缺乏更多，其中一些——這些索賠的收據比商業計劃和其他計劃要多得多。那麼——我們基本上有我們的估計，我們基本上看到的是我們收到的索賠低於我們的預期。所以這 - 現在可能有很多原因，但在這個時間點，我們基本上也在思考，好吧，因為我們不僅在看過去，但這對我們意味著什麼正在查看我們在第一季度和今年剩餘時間的應計項目，以及我們在查看全年時從醫療補助計劃中受益的原因。

Great. Thank you, Enrique. Sue?

偉大的。謝謝你，恩里克。起訴？

Yes. Steve, no, the pancreatic study was actually went to the final endpoint, and we stopped study. So I think you might be looking atct.gov where we might have had a later time line just as we're looking at future follow-up with patients. It does not, by any means, reduce our confidence in moving forward in other indications for the abema. This is pretty high bar, pancreatic, we know is a tough tumor type. And we are looking at clearly targeting tumors where the CDK pathway is important, and also, we do believe the combinations is probably the way to go. We have a number of non-breast indications that we are looking at, and you should see some trials starting later this year as well as, of course, our life cycle planning in breast cancer.

是的。史蒂夫，不，胰腺研究實際上已經到了最終終點，我們停止了研究。因此，我認為您可能正在查看 atct.gov，我們可能會在以後的時間線中查看，就像我們正在研究未來對患者的隨訪一樣。無論如何，它不會降低我們在其他跡象表明阿貝馬前進的信心。這是相當高的標準，胰腺，我們知道是一種堅韌的腫瘤類型。我們正在研究明確靶向 CDK 途徑很重要的腫瘤，而且我們確實相信這些組合可能是要走的路。我們正在研究一些非乳腺癌適應症，您應該會看到今年晚些時候開始的一些試驗，當然還有我們在乳腺癌方面的生命週期規劃。

Great. Thank you. I think we've gotten through 17 different sets of questions. And it sounds like there's no more folks in the queue. So I'll turn it over to Dave Ricks to close our session. And Leaha, after that, you can provide the replay instruction.

偉大的。謝謝你。我想我們已經解決了 17 組不同的問題。聽起來隊列中沒有更多人了。所以我將把它交給 Dave Ricks 來結束我們的會議。而Leaha，在那之後，你可以提供回放指令。

Thanks, Phil. We appreciate all of your participation in today's earnings call and your interest in Eli Lilly and Company. Our strong first quarter results represent continued progress on top line and bottom line growth prospects, and we have raised our guidance as a result. We have a broad portfolio of new products with many life cycle opportunities driving top line growth, hopefully for years to come. And we are executing on our significant margin expansion opportunities. Together with a strong pipeline, Lilly continues to be a compelling investment. Please follow up with our Investor Relations team with your questions we have not addressed on today's call. That concludes the call. Have a great day, everyone.

謝謝，菲爾。我們感謝您參加今天的財報電話會議以及您對禮來公司的興趣。我們強勁的第一季度業績代表了頂線和底線增長前景的持續進步，因此我們提高了我們的指導。我們擁有廣泛的新產品組合，具有許多推動收入增長的生命週期機會，有望在未來幾年內實現增長。我們正在執行我們重要的利潤率擴張機會。加上強大的管道，禮來繼續成為一項引人注目的投資。請就您在今天的電話會議中未解決的問題與我們的投資者關係團隊聯繫。這結束了通話。祝大家有個美好的一天。

Ladies and gentlemen, this conference is available for digitized replay after 11:30 a.m. Eastern Time today for 1 year through May 24, 2019, at midnight. You may access the replay service at any time by calling 1 (800) 475-6701 and enter the access code 446232. International participants may dial (320) 365-3844. And that does conclude your conference for today. Thank you for your participation and for using AT&T TeleConference Service. You may now disconnect.

女士們先生們，本次會議可在東部時間今天上午 11:30 之後進行數字化重播，為期 1 年，直至 2019 年 5 月 24 日午夜。您可以隨時撥打 1 (800) 475-6701 並輸入訪問代碼 446232 訪問重播服務。國際參與者可以撥打 (320) 365-3844。這確實結束了您今天的會議。感謝您的參與和使用 AT&T 電話會議服務。您現在可以斷開連接。