施貴寶 (BMY) 2013 Q1 法說會逐字稿

Good day, and welcome to today's first-quarter earnings 2013 earnings release conference call. This call is being recorded. At this time I would like to turn call over Mr. John Elicker, Senior Vice President, Investor Relations and Public Affairs. Please go ahead, Mr. Elicker.

大家好，歡迎參加今天的 2013 年第一季度財報電話會議。此通話正在錄音。現在我想請投資者關係和公共事務高級副總裁 John Elicker 先生來發言。請繼續，埃利克先生。

Thank you, Kayla, and good morning everybody.

謝謝你，凱拉，大家早上好。

Thanks for joining us to review our first-quarter results. Unfortunately, Lamberto Andreotti, our CEO, is not able to join us this morning. He is attending to an urgent family health matter. With me this morning are Charlie Bancroft, our Chief Financial Officer. Charlie will have prepared remarks. And then joining him for Q&A are Elliott Sigal, our Chief Scientific Officer; Francis Cuss, our incoming Chief Scientific Officer; Giovanni Caforio, President of the US Business; and Beatrice Cazala, Executive Vice President, Commercial Operations.

感謝您與我們一起回顧我們第一季度的業績。不幸的是，我們的首席執行官 Lamberto Andreotti 今天早上無法加入我們。他正在處理緊急的家庭健康問題。今天早上和我在一起的是我們的首席財務官查理·班克羅夫特。查理將準備好講話。然後與他一起參加問答的是我們的首席科學官 Elliott Sigal； Francis Cuss，我們即將上任的首席科學官； Giovanni Caforio，美國商業總裁；和商業運營執行副總裁 Beatrice Cazala。

So, before we get started, let me just take care of some of the legal requirements. During the call, we will make statements about the Company's future plans and prospects that constitute forward-looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Company's SEC filings. These forward-looking statements represent our estimates as of today and should not be relied upon as representing our estimates as of any subsequent date.

因此，在我們開始之前，讓我先介紹一些法律要求。在電話會議期間，我們將就公司的未來計劃和前景發表聲明，這些聲明構成《私人證券訴訟改革法案》安全港條款中的前瞻性聲明。由於各種重要因素（包括公司向 SEC 文件中討論的因素），實際結果可能與這些前瞻性陳述所示的結果存在重大差異。這些前瞻性陳述代表了我們截至目前的估計，不應被視為代表我們截至任何後續日期的估計。

We specifically disclaim any obligation to update forward-looking statements, even if our estimates change. We will also discuss non-GAAP financial measures adjusted to exclude certain specified items. Reconciliations of these non-GAAP financial measures to the most comparable GAAP measures are available on our website.

即使我們的估計發生變化，我們特別不承擔任何更新前瞻性陳述的義務。我們還將討論調整後的非公認會計原則財務指標，以排除某些特定項目。我們的網站上提供了這些非公認會計準則財務指標與最具可比性的公認會計準則財務指標的調節表。

Charlie?

查理？

Thank you, John, and good morning, everyone.

謝謝約翰，大家早上好。

We have just completed a good start to an important year, one in which our focus is on commercial execution, as well as the continued delivery of our diverse and sustainable pipeline. Before going into deeper dive on our financial performance, I would like to highlight three important areas -- Eliquis, diabetes, and R&D.

我們剛剛完成了重要的一年的良好開端，這一年我們的重點是商業執行，以及我們多樣化和可持續管道的持續交付。在深入探討我們的財務業績之前，我想強調三個重要領域——Eliquis、糖尿病和研發。

We are off to a very good start with Eliquis. Eliquis's differentiated clinical profile is being recognized and valued by physicians, payers, and patients. In the US, we're on track with our expectations. Trends are consistent with where we thought they would be, and access is actually a little ahead of expectations. We expect to see continued progress in the second quarter with commercial, Medicare part D, and hospital plant. We expect the impact of this will start to be reflected in the prescription trends over the course of this year.

Eliquis 為我們帶來了良好的開端。Eliquis 的差異化臨床特徵正在得到醫生、付款人和患者的認可和重視。在美國，我們正在實現我們的期望。趨勢與我們的預期一致，而且訪問實際上有點超出預期。我們預計第二季度商業、醫療保險 D 部分和醫院工廠將繼續取得進展。我們預計這一影響將開始反映在今年的處方趨勢中。

Outside the US, we are in the early stages, but we have made progress on the access front in Europe, with a positive recommendation from the UK and a positive guidance from Germany. In other markets, the process is ongoing, with multiple negotiations taking place. With our partner Pfizer, we are very focused on executing the global launch of Eliquis, with its A-fib indication. We continue to believe that Eliquis will be the leading new agent over time.

在美國之外，我們還處於早期階段，但在英國的積極建議和德國的積極指導下，我們在歐洲的准入方面已經取得了進展。在其他市場，這一過程正在進行中，正在進行多次談判。與我們的合作夥伴輝瑞公司一起，我們非常專注於執行 Eliquis 的全球上市，該藥物具有房顫適應症。我們仍然相信，隨著時間的推移，Eliquis 將成為領先的新藥。

With respect to our diabetes portfolio, we continue to make good progress in this area as well. In the US, we have fully aligned with AstraZeneca, having finalized our sales and marketing team. The combined organization is now focused solely on serving the needs of diabetes patients. We completed the international commercial integration of Amylin on April 1 in nearly 90 markets, a complex process that impacted all aspects of our Business. This is a significant accomplishment for the BMS-AZ alliance. With the integration work nearly done, we can now redouble our efforts in diabetes to ensure we are focused and able to capitalize on the opportunities we have, including plans to file Forxiga for regulatory review in the US in the middle of the year.

就我們的糖尿病產品組合而言，我們也在該領域繼續取得良好進展。在美國，我們已與阿斯利康完全合作，確定了我們的銷售和營銷團隊。合併後的組織現在只專注於滿足糖尿病患者的需求。我們於 4 月 1 日在近 90 個市場完成了 Amylin 的國際商業整合，這是一個影響我們業務各個方面的複雜過程。這是 BMS-AZ 聯盟的一項重大成就。隨著整合工作接近完成，我們現在可以在糖尿病領域加倍努力，以確保我們集中精力並能夠利用我們所擁有的機會，包括計劃在今年年中向美國監管部門提交 Forxiga 申請。

With respect to R&D, 2013 is another important year for the presentation of key clinical data that will lay the foundation for our Company's future growth. We plan to present new PD-1 data at ASCO. PD-1 has received fast-track status from the FDA for lung, renal cell, and melanoma. The top line results for Savor, our CV outcomes trial for Onglyza, should be available in June. And in hep C, you may have seen the important data on our triple regimen presented at ESAL this week, and we expect to initiate Phase 3 in a fixed-dose combination by the end of the year. As mentioned in our press release this morning, we have received breakthrough status from the FDA for this program. Also, by the end of the year, we plan to file our all-dual oral regimen for regulatory review in Japan.

在研發方面，2013年是關鍵臨床數據呈現的又一個重要年份，將為公司未來的發展奠定基礎。我們計劃在 ASCO 上展示新的 PD-1 數據。PD-1 已獲得 FDA 的針對肺、腎細胞和黑色素瘤的快速通道資格。Savor 的主要結果（我們針對 Onglyza 的 CV 結果試驗）將於 6 月公佈。對於丙肝，您可能已經看到了本週在 ESAL 上公佈的我們三聯療法的重要數據，我們預計在今年年底前啟動固定劑量組合的 3 期臨床試驗。正如我們今天早上的新聞稿中提到的，我們已獲得 FDA 對該項目的突破性地位。此外，我們計劃在今年年底前將我們的全雙口服療法提交日本監管審查。

Now, let me discuss our first quarter financial performance. We delivered net sales of $3.8 billion, down 27% compared to the first quarter of last year, due to the loss of exclusivity of Plavix and Avapro. We will continue to see the impact of these exclusivity losses on our financial results for one more quarter. Excluding Plavix and Avapro, global sales grew 10%, led by Yervoy, Orencia, our diabetes portfolio, Baraclude, and Sprycel. I will touch on some key product highlights. Yervoy global sales increased 49% to $229 million. This includes the positive impact from a $25 million, one-time reversal of deferred revenues in the US. You will recall that we established this sales deferral in the third quarter of 2011.

現在，讓我討論一下我們第一季度的財務業績。由於失去 Plavix 和 Avapro 的獨家經營權，我們的淨銷售額為 38 億美元，比去年第一季度下降 27%。我們將在接下來的一個季度繼續看到這些獨家經營權損失對我們財務業績的影響。不包括 Plavix 和 Avapro 在內，全球銷售額增長了 10%，其中 Yervoy、Orencia、我們的糖尿病產品組合、Bararude 和 Sprycel 領先。我將談談一些關鍵的產品亮點。Yervoy 全球銷售額增長 49%，達到 2.29 億美元。這包括美國 2500 萬美元一次性逆轉遞延收入帶來的積極影響。您可能還記得，我們​​在 2011 年第三季度就確定了這一銷售延期。

Excluding this adjustment for Yervoy, US sales increased 15% versus last year. We are seeing good growth across all segments, including community hospitals and practices, as physicians increasingly understand the potential for long-term survival. We expect continued growth in both the US and Europe, where we now have reimbursement in essentially all markets.

排除 Yervoy 的這一調整，美國銷售額比去年增長了 15%。隨著醫生越來越了解長期生存的潛力，我們看到包括社區醫院和診所在內的所有領域都出現了良好的增長。我們預計美國和歐洲的業務將持續增長，目前我們幾乎在所有市場都提供報銷服務。

Orencia global sales increased 26% to $320 million. Orencia continues to perform well globally, with growing demand in the US and Europe, as we expand access, reimbursement, and promotion for the subcu formulation. US sales increased 25% compared to last year, driven by strong demand for subcu, with reported sales of $70 million in the quarter. Several months into the subcu launch in Europe, we are seeing strong uptake in Germany and the rest of northern Europe, and we continue to secure access and reimbursement in other parts of Europe.

Orencia 全球銷售額增長 26%，達到 3.2 億美元。隨著我們擴大 subcu 配方的准入、報銷和推廣，Orencia 在全球範圍內繼續表現良好，美國和歐洲的需求不斷增長。受 subcu 強勁需求的推動，美國銷售額與去年相比增長了 25%，據報告，本季度銷售額為 7000 萬美元。subcu 在歐洲推出幾個月後，我們看到德國和北歐其他地區的使用率強勁，並且我們繼續確保歐洲其他地區的使用和報銷。

Orencia also continues to perform well in Japan, up 31% versus last year, and we are waiting for a regulatory decision on subcu. In diabetes, global sales for the Onglyza franchise increased 25% to $202 million. Although Onglyza's new prescription trends in the US flattened somewhat this past quarter, we saw strong volume growth for the Onglyza franchise versus the prior year.

Orencia 在日本也繼續表現良好，比去年增長了 31%，我們正在等待有關 subcu 的監管決定。在糖尿病領域，Onlyza 特許經營權的全球銷售額增長了 25%，達到 2.02 億美元。儘管上個季度 Onglyza 在美國的新處方趨勢有所放緩，但我們看到 Onglyza 特許經營權與上一年相比銷量強勁增長。

US sales for our Exenatide franchise were $136 million. Bydureon sales volume and market share continued to grow during the quarter, fueled primarily by primary care physicians as we broaden Bydureon's prescriber base. For Byetta, we are focused on opportunities to combine the short-acting insulin. We launched Forxiga in Germany, the UK, and Denmark during the quarter, and as I mentioned, we hope to file for US regulatory approval by midyear. Sprycel global sales increased 24% to $287 million. In a very competitive market, Sprycel continues to gain market share, particularly in the first line setting. Also included in our total sales figure is a positive $36 million impact from prior year Medicaid accrual adjustments.

我們的艾塞那肽特許經營權在美國的銷售額為 1.36 億美元。隨著我們擴大 Bydureon 的處方者基礎，Bydureon 的銷量和市場份額在本季度繼續增長，這主要是由初級保健醫生推動的。對於Byetta，我們專注於結合短效胰島素的機會。我們在本季度在德國、英國和丹麥推出了 Forxiga，正如我提到的，我們希望在年中之前向美國監管機構申請批准。Sprycel 全球銷售額增長 24%，達到 2.87 億美元。在競爭非常激烈的市場中，Sprycel 不斷獲得市場份額，特別是在一線環境中。我們的總銷售額還包括上一年醫療補助應計調整產生的 3600 萬美元的積極影響。

Now let me highlight a few items from the rest of our P&L. I will focus my remarks on our non-GAAP results. As John mentioned, reconciliations to our GAAP results are available in our press release and on our website. Gross margin was 74.5% during the quarter, down 70 basis points compared to the same period last year. This decrease is primarily due to the change in terms for Abilify and product mix, particularly the Exenatide franchise. R&D expense was $930 million, which is up 9% compared to last year. The increase in spend was largely due to the Amylin acquisition and increased portfolio spend, including PD-1 and hep C. Our non-GAAP tax rate was 11% during the quarter. This is lower than our full-year guidance, largely due to booking in the entire 2012 R&D tax credit in the quarter.

現在讓我重點介紹損益表其餘部分中的一些項目。我的評論將重點關注我們的非公認會計準則業績。正如約翰提到的，我們的 GAAP 結果的調節可在我們的新聞稿和我們的網站上找到。該季度毛利率為74.5%，較去年同期下降70個基點。這一下降主要是由於 Abilify 和產品組合的變化，特別是艾塞那肽特許經營權。研發費用為9.3億美元，比去年增長9%。支出的增加主要是由於 Amylin 收購和投資組合支出的增加，包括 PD-1 和丙肝。本季度我們的非 GAAP 稅率為 11%。這低於我們的全年指引，主要是由於本季度計入了整個 2012 年研發稅收抵免。

Moving to guidance, we are confirming our full-year 2013 GAAP and non-GAAP EPS guidance range. In addition, our line item guidance remains unchanged. Our guidance assumes current exchange rates. As you know, foreign currencies have weakened against the dollar since we originally gave 2013 guidance in January, particularly the yen. While we saw no net impact from exchange in the first quarter compared to last year, at current rates we would expect to see some pressure through the remainder of the year.

轉向指導，我們正在確認 2013 年全年 GAAP 和非 GAAP EPS 指導範圍。此外，我們的訂單項指導保持不變。我們的指導假設當前匯率。如您所知，自從我們最初在 1 月份給出 2013 年指引以來，外幣兌美元匯率已經走弱，尤其是日元。雖然與去年相比，我們沒有看到第一季度匯率的淨影響，但按照目前的匯率，我們預計今年剩餘時間將面臨一些壓力。

So taken together, this is an important time for Bristol-Myers Squibb. We are in full transition to the portfolio of the future, a transition that is moving forward on two parallel tracks. Executing our near-term commercial opportunities, and at the same time, developing a pipeline to deliver long-term, sustainable growth.

綜合來看，這對於百時美施貴寶來說是一個重要的時刻。我們正在全面過渡到未來的投資組合，這一過渡正在兩條平行的軌道上向前推進。抓住我們的近期商業機會，同時開發渠道以實現長期、可持續的增長。

Before we turn it over to your questions, I want to take a moment to offer my personal congratulations to Elliott, and wish him well in his retirement. I have had the privilege of working with Elliot for a long time and truly value his many contributions to our Company.

在我們向你們提問之前，我想花點時間向埃利奧特表示個人祝賀，並祝愿他退休後一切順利。我有幸與 Elliot 長期合作，並非常重視他對我們公司的許多貢獻。

I would also like to congratulate Francis on his appointment to Chief Scientific Officer. Francis and I have also worked together for quite some time. Francis is a respected leader with broad experience in both research and development. I look forward to continued collaboration with Francis to help our Company deliver an innovative and diverse pipeline of medicines.

我還要祝賀弗朗西斯被任命為首席科學官。弗朗西斯和我也合作了一段時間。弗朗西斯是一位受人尊敬的領導者，在研究和開發方面擁有豐富的經驗。我期待與弗朗西斯繼續合作，幫助我們公司提供創新和多樣化的藥物產品線。

At this time, we would be happy to answer your questions.

此時，我們很樂意回答您的問題。

Thanks, Kayla.

謝謝，凱拉。

I we are ready to go to questions and I will just remind everybody in addition to Charlie, we have Elliott and Francis on the R&D side, as well as the Giovanni and Beatrice here to answer any commercial questions that you might have. Kayla?

我們已經準備好提問，我只想提醒大家，除了查理之外，我們還有研發方面的埃利奧特和弗朗西斯，還有喬瓦尼和比阿特麗斯，他們可以回答你們可能遇到的任何商業問題。凱拉？

Thank you.

謝謝。

(Operator Instructions)

（操作員說明）

Jami Rubin, Goldman Sachs.

賈米·魯賓，高盛。

This is for Elliott and Francis. Can you comment on your PD-1 program in the context of fast track status versus breakthrough designation? There seems to be some confusion in the marketplace. And then to that end, you did receive breakthrough status for your triple DAA hep C therapy, which is interesting, because I know that Gilead didn't receive breakthrough status. So, what you think this all means? And then, secondarily, we did see some early data on Roche's PD-L1. Interested in your take and how you see that comparing to your PD-1? Thanks.

這是給埃利奧特和弗朗西斯的。您能否從快速通道狀態與突破性指定的角度對您的 PD-1 項目進行評論？市場上似乎存在一些混亂。為此，您的三聯 DAA 丙型肝炎療法確實獲得了突破性進展，這很有趣，因為我知道吉利德沒有獲得突破性進展。那麼，你認為這一切意味著什麼？其次，我們確實看到了羅氏 PD-L1 的一些早期數據。對您的看法以及與您的 PD-1 相比有何看法感興趣？謝謝。

Thank you, Jami. This is Elliott. I will start and Francis will chime in. I agree that people are trying to figure out the exact implications of the new designation of breakthrough therapy. It's a new tool that we all welcome for the FDA. Its implications are going to evolve. And it has added to a host of other existing tools.

謝謝你，賈米。這是埃利奧特。我將開始，弗朗西斯將插話。我同意人們正在試圖弄清楚突破性療法的新名稱的確切含義。這是 FDA 我們都歡迎的新工具。它的影響將會不斷演變。它還添加到了許多其他現有工具中。

My impression is that it is an opportunity for early programs to receive regular interaction with the FDA and to gain input on the development of the registrational program. So, to that end, we certainly welcome the breakthrough designation on our triple regimen in hepatitis C. This is a Phase II program. I can only speculate that the FDA was attracted to this because it is a non-nuke-base regimen. It has no Ribavirin, potentially, and has no Ritonavir. But again, the implications are not clear. The FDA oncology division has historically identified programs and use all the tools, including fast track and other tools, to their advantage to advance programs that can benefit patients in the areas of unmet need. Fast track is what we took advantage of in three tumor types.

我的印像是，這是早期項目與 FDA 定期互動並獲得註冊項目開發投入的機會。因此，為此，我們當然歡迎丙型肝炎三聯療法的突破性指定。這是一個 II 期項目。我只能推測 FDA 之所以對此感興趣，是因為它是一種非核武器治療方案。它可能不含利巴韋林，也不含利托那韋。但同樣，其影響尚不清楚。FDA 腫瘤學部門歷來已確定項目並使用所有工具，包括快速通道和其他工具，以發揮其優勢來推進項目，使未滿足需求領域的患者受益。我們在三種腫瘤類型中利用了快速通道。

And over the last year or so, we have had, in my opinion, very high-quality frequent interactions, great input, and have moved from a standing start, as I call it, from a Phase I into six registrational trials, including five randomized Phase III programs. So I am very pleased with where we are. I acknowledge that the field is competitive. We were attracted to this field back in 2004 and have been developing the science that is leading the way, but it is a competitive field. Our program is broad, comprehensive, and multiple tumor types, and has multiple opportunities for acceleration and early approvals. Francis, would you like to add to that?

在我看來，在過去一年左右的時間裡，我們進行了非常高質量的頻繁互動和大量投入，並且已經從我所說的一期臨床試驗轉變為六項註冊試驗，其中包括五項註冊試驗。隨機化 III 期項目。所以我對我們現在的處境非常滿意。我承認這個領域是競爭激烈的。我們早在 2004 年就被這個領域所吸引，並一直在開發引領潮流的科學，但這是一個競爭激烈的領域。我們的項目廣泛、全面、多種腫瘤類型，並有多種加速和早期批准的機會。弗朗西斯，你想補充一下嗎？

Certainly. I am certainly very excited talking going -- moving to the HCV program for the recent data presented at ESAL. As you're well aware, this is a non-Interferon, non-Riba, non-Ritonavir triple. And we showed very impressive efficacy data in a well-tolerated regimen. And I think we have had numerous and very good interactions with the FDA. And I think it reflects the potential importance they see in this regimen because of its profile.

當然。我當然非常興奮談論即將到來的 HCV 項目，以獲取 ESAL 上提供的最新數據。如您所知，這是一種不含干擾素、不含Riba、不含利托那韋的三聯藥物。我們在耐受性良好的方案中展示了非常令人印象深刻的療效數據。我認為我們與 FDA 進行了多次非常良好的互動。我認為這反映了他們在這個養生法中看到的潛在重要性，因為它的外形。

We also have the advantage here of being able to move quickly. We've accelerated the Phase IIIs into the fourth quarter of this year. And confident we will have a fixed-dose combination to take into Phase III, which will be, presumably, a simple one-tablet, twice-a-day regimen for 12 weeks.

我們在這裡還具有能夠快速行動的優勢。我們已將第三階段加速到今年第四季度。我們相信我們將有一個固定劑量組合進入 III 期，這大概是一個簡單的、每天兩次、每次 1 片的治療方案，持續 12 週。

Just moving to PD-1, PD-L1. As you know, we published in the New England Journal last year our experience, both with PD-1 and PD-L1. We have the advantage of being the only company that's been able to look at both of these regimens. And based on the data we saw, both efficacy and safety, we are moving forward with PD-1, with an opportunity to accelerate that forward. I think it's important to note that we also talked about biomarkers in those publications, and we will be looking at biomarkers. But we have left ourselves open to the option of a program that doesn't necessarily rely on a biomarker and the data that will support it.

剛剛轉向 PD-1、PD-L1。如您所知，我們去年在《新英格蘭雜誌》上發表了我們在 PD-1 和 PD-L1 方面的經驗。我們的優勢是成為唯一一家能夠研究這兩種療法的公司。根據我們看到的有效性和安全性數據，我們正在推進 PD-1，並有機會加速這一進程。我認為值得注意的是，我們還在這些出版物中討論了生物標誌物，並且我們將關註生物標誌物。但我們對程序的選擇持開放態度，該程序不一定依賴於生物標記物和支持它的數據。

Thank you, Jami. Kayla, can we go to the next question please?

謝謝你，賈米。凱拉，我們可以進入下一個問題嗎？

Tim Anderson, Sanford Bernstein.

蒂姆·安德森，桑福德·伯恩斯坦。

Again, on PD-1, my understanding is that you can get both fast track and breakthrough. And my question is, did you ask for breakthrough designation, and is that request still pending, or have you been denied? I don't think it really means that much, but it is a little bit unusual that Merck got that designation, because your compound is the one that is in the press a lot.

再說一次，在PD-1上，我的理解是你可以同時獲得快速通道和突破。我的問題是，您是否要求突破性指定，該請求是否仍在等待中，或者是否已被拒絕？我認為這並沒有多大意義，但是默克公司獲得這個稱號有點不尋常，因為你的化合物是媒體上經常報導的化合物。

And then a question on dosing and Phase III, if I understand the dosing right, it's 3 mg per kg. I think in Phase II you went all the way up to 10 mgs per kg. Is there a dose-limiting toxicity with the drug? And if so, what is it? Or maybe asked differently, are there any dose-dependent side effects with the product? Then, just on your comment about -L1 versus -1. Are you saying that you saw worse safety with your PD-L1?

然後是關於劑量和第三階段的問題，如果我理解劑量正確的話，它是每公斤3毫克。我想在第二階段，你的劑量一直達到了每公斤 10 毫克。該藥物是否存在劑量限制性毒性？如果是的話，那是什麼？或者可能會問，該產品是否有任何劑量依賴性副作用？然後，就您對 -L1 與 -1 的評論。您是說您發現 PD-L1 的安全性更差嗎？

Okay, Tim, this is Elliott, and Francis will follow. I will deal with the different classifications that you talked about, and Francis will address the fact that we are selecting a dose. With regard to the dose side effects, the choice of PD-1 versus PD-L1 and the different ligands. It is true that these different designations, including fast track and breakthrough, are not mutually exclusive. And I think, however, the way I'm viewing this, I am very pleased with the interactions we have had when our program was at an earlier stage. And now has a well-designed, broad set of possibilities for indications, early approval, acceleration. These designations don't convey any guarantee for downstream action, like early approval, priority review, etcetera. But our program is designed to take advantage of the full array of opportunities here.

好的，蒂姆，這是埃利奧特，弗朗西斯將跟隨。我將處理你談到的不同分類，弗朗西斯將解決我們正在選擇劑量的事實。關於劑量副作用、PD-1 與 PD-L1 的選擇以及不同配體。確實，這些不同的名稱，包括快速通道和突破，並不是相互排斥的。然而，我認為，就我看待這一問題的方式而言，我對我們在項目早期階段進行的互動感到非常滿意。現在擁有一系列精心設計的、廣泛的適應症、早期批准、加速的可能性。這些指定並不為下游行動提供任何保證，例如早期批准、優先審查等。但我們的計劃旨在充分利用這裡的全部機會。

Tim, thank you. Just on the dose of Nivolumab, we obviously tested comprehensively different doses, and as always, we make an analysis of the best therapeutic index. So, our analysis, taken together with the dosing regimen, came out that three was the optimal dose. As far as PD-L1, versus PD-1 is concerned, you can certainly read the data we presented last year in the New England Journal. I will tell you as an overview, we have seen similar toxicities for both PD-1 and PD-L1 of similar degree. So, our analysis was, we were somewhat ahead on PD-1. There was a suggestion, perhaps, of greater efficacy, but of course it's very early studies, and we were able to accelerate PD-1 forward. Thank you.

蒂姆，謝謝你。就納武單抗的劑量而言，我們顯然對不同劑量進行了綜合測試，並一如既往地對最佳治療指標進行了分析。因此，我們的分析與給藥方案一起得出結論，三是最佳劑量。就 PD-L1 與 PD-1 而言，您當然可以閱讀我們去年在《新英格蘭雜誌》上提供的數據。我將概述一下，我們已經看到 PD-1 和 PD-L1 具有相似程度的相似毒性。因此，我們的分析是，我們在 PD-1 方面領先一些。也許有人建議更有效，但當然這是非常早期的研究，我們能夠加速 PD-1 的發展。謝謝。

Great, thank you Tim. Can we go to the next question, please, Kayla?

太好了，謝謝蒂姆。凱拉，我們可以進入下一個問題嗎？

Seamus Fernandez, Leerink.

謝默斯·費爾南德斯，萊林克。

Thanks. Maybe just have a temporary break from PD-1, but I will get back to it. The Eliquis launch, can we talk a little bit about how you guys are thinking about the potential for an acceleration? We have seen a really material acceleration in Xarelto scripts, roughly about 12 months into the launch. So, just wondering if, again, given your statements earlier, if we can anticipate a similar-type acceleration?

謝謝。也許只是暫時脫離 PD-1，但我會繼續做下去。Eliquis 的推出，我們能談談你們如何看待加速的潛力嗎？我們看到 Xarelto 腳本在發布大約 12 個月後出現了真正的實質性加速。那麼，只是想知道，根據您之前的陳述，我們是否可以預期類似的加速？

And then separately, on PD-1, just a couple of questions there. Can you talk a little bit about the -- what could be a potential issue, if any, with utilizing a modified IgG1? So again, the immunoglobulin that is attached to Roche's PD-L1 versus the choice of an IgG4. There are suggestions that perhaps, that that may be an important difference, although I think there may be some limitations there. And then lastly, have you seen any responses in colorectal cancer with either your PD-1 or PD-L1. It looks like there may be some responses in colorectal cancer with Roche's drug, and I didn't know if you saw certain ways, or potential ways, to open up that very large tumor type with immunotherapy. Thank you.

然後分別就 PD-1 提出幾個問題。您能否談談使用修飾的 IgG1 可能存在的潛在問題（如果有）是什麼？再說一遍，羅氏 PD-L1 附著的免疫球蛋白與 IgG4 的選擇。有人建議這可能是一個重要的區別，儘管我認為可能存在一些限制。最後，您是否發現 PD-1 或​​ PD-L1 對結直腸癌有任何反應？看起來羅氏的藥物可能對結直腸癌有一些反應，我不知道你是否看到了某些方法或潛在的方法，可以通過免疫療法打開這種非常大的腫瘤類型。謝謝。

Thanks, Seamus. This is Charlie. Let me talk a little bit of a brief overview on Eliquis and then I will pass it over to Giovanni. He can talk more specifically about the US. Feedback has been universally positive on Eliquis's clinical profile. And although we are still at the early stages of our launch, we continue to believe Eliquis will be the leading new agent in this market over time.

謝謝，西莫。這是查理。讓我簡單介紹一下 Eliquis，然後我會將其轉交給 Giovanni。他可以更具體地談論美國。Eliquis 的臨床概況得到了普遍積極的反饋。儘管我們仍處於推出的早期階段，但我們仍然相信 Eliquis 隨著時間的推移將成為該市場領先的新藥。

We also have some near-term lifecycle plans for Eliquis. We plan to file for potential VTE prevention indication with the FDA this summer. And in addition, we expect to present the data from the Amplify study at IFPH. And we'll potentially file for VTE treatment indication by the end of the year. Obviously, pending the results of that study. Giovanni?

我們還有一些 Eliquis 的近期生命週期計劃。我們計劃今年夏天向 FDA 申請潛在的 VTE 預防適應症。此外，我們希望在 IFPH 上展示 Amplify 研究的數據。我們可能會在今年年底前申請 VTE 治療指徵。顯然，正在等待該研究的結果。喬瓦尼？

Yes, good morning, Seamus. This is Giovanni. Just to follow up on what Charlie said. As you know, we have been working with Pfizer in promoting Eliquis in the US since the beginning of February. And so far, although its early, clearly, the launch has been going very well and very much in line with our expectations. We have positive feedback from our customers on the differentiated profile of Eliquis.

是的，早上好，西莫。這是喬瓦尼。只是為了跟進查理所說的話。如您所知，自二月初以來，我們一直在與輝瑞合作在美國推廣 Eliquis。到目前為止，儘管還為時過早，但顯然，發布進展順利，非常符合我們的預期。我們的客戶對 Eliquis 的差異化特徵給予了積極的反饋。

And let me give you a couple of comments about early indicators. When we started our focus on the launch, we focused on access. We focused on hospital formulary listing and stocking. That's important, as you know, because over 50% of initiations are in the hospital. And also, we started promoting with cardiologists and with a group of early adopter PCPs. From an access perspective, as Charlie mentioned in the introductory remarks, we are doing as well, and maybe a bit better, than we had planned.

讓我對早期指標提出一些評論。當我們開始關注發佈時，我們專注於訪問。我們專注於醫院處方列表和庫存。如您所知，這很重要，因為超過 50% 的啟動活動是在醫院進行的。此外，我們開始向心髒病專家和一群早期採用者 PCP 進行推廣。從訪問的角度來看，正如查理在介紹性發言中提到的那樣，我們做得也很好，也許比我們計劃的要好一些。

Right now we have coverage in approximately 90% of commercial lives, and in approximately 60% of Medicare lives. Importantly, we have covered status with all five top Medicare part D plans, and with three of those five, we have actually achieved preferred status. So that is going in line with our plans and, obviously, we are continuing to work on that. From a hospital perspective, we are continuing to make progress. We had a very large number of P&T committee reviews in April. There are many more planned for the month of May. That is going well and will continue to improve over time.

目前，我們覆蓋了大約 90% 的商業生活和大約 60% 的醫療保險生活。重要的是，我們已經涵蓋了所有五個頂級 Medicare D 部分計劃的狀態，並且對於這五個計劃中的三個，我們實際上已經達到了優先狀態。因此，這符合我們的計劃，顯然，我們正在繼續努力。從醫院的角度來看，我們正在不斷取得進展。4 月份，我們進行了大量 P&T 委員會審查。五月還有更多計劃。這一切進展順利，並將隨著時間的推移繼續改善。

In terms of our promotion to physicians, the efficacy and safety profile of Eliquis is really resonating very well. The top [anated] recalled messages are really around efficacy and safety and the three end points. Which is different from other agents which are been prescribed primarily because of convenience, on the contrary. So, we see that all of the leading indicators are in line with our expectations. They are very positive, and that clearly reinforces our belief that Eliquis will become, over time, the leading agent in the indication, and that clearly would result in growth over the course of the year and into next year.

就我們向醫生的推廣而言，Eliquis 的功效和安全性確實引起了很好的共鳴。最重要的[註釋]召回信息實際上是圍繞功效和安全性以及三個終點。相反，這與主要因為方便而開處方的其他藥物不同。因此，我們看到所有領先指標都符合我們的預期。他們非常積極，這顯然強化了我們的信念，即隨著時間的推移，Eliquis 將成為該適應症的領先藥物，這顯然會導致今年和明年的增長。

Seamus, this is Elliott. With regard to your question of applicability of the PD-1 pathway in other tumors. Early on, we began exploring the possibility and the likelihood that this could be very broad based, and we feel that is going to turn out to be true. We have a program where we're exploring other tumor types. And we will be presenting that data down the line. Right now, as you know, the focus is on kidney, lung, and melanoma, with about six or seven registrational trials and a broad-based program.

西莫，這是埃利奧特。關於你的PD-1通路在其他腫瘤中的適用性問題。早些時候，我們開始探索這種可能性以及這種可能性的基礎非常廣泛，我們認為這將成為現實。我們有一個項目正在探索其他腫瘤類型。我們將在後續展示這些數據。如您所知，目前的重點是腎臟、肺和黑色素瘤，約有六到七個註冊試驗和一個基礎廣泛的計劃。

Your second question dealt with the isotype of the antibody. And our research scientists in California that originally came from [Vetorex] have done perhaps the most work on the relevance of the isotype in selecting these immune modulators, with positive and negative features sometimes are chosen. And they are very confident that we have chosen an optimal isotype for PD-1. I will let Francis add his comments to that work that has been ongoing under him.

你的第二個問題涉及抗體的同種型。我們在加利福尼亞州的研究科學家最初來自 [Vetorex]，他們在選擇這些免疫調節劑時可能對同種型的相關性做了最多的工作，有時會選擇積極和消極的特徵。他們非常有信心我們為 PD-1 選擇了最佳同種型。我將讓弗朗西斯將他的評論添加到他領導下正在進行的這項工作中。

Yes, thank you, Elliott. A couple of things to mention. As you know, our monitor antibody comes from the humani-- the [XeNa] mouse model developed by Nils Lonberg and his colleague at -- formerly of Medarex. So we have a fully human antibody. It's an IgG4 antibody, and the mutation in the hinge region to make a consensus for IgG1. There has been some suggestion by others that there may be some [ADC]. There is absolutely none in our in vitro, and we have not seen anything in the clinic. I think it's important to also look at the immunogenicity of these antibodies. And ours being a fully human antibody, we see very low immunogenicity in the nearly 1000 patients we have treated now. I think, as you mentioned, the [genocet] antibodies, that's of course a CDR grafted antibody and I think it's, again, important. It has a different target, not immune cells. And so, one should look carefully at the immunogenicity. And one measure of that, of course, is what your dose is. And we have, as we just mentioned in the previous question, a low dose, which reflects the low immunogenicity. So let me stop there.

是的，謝謝你，埃利奧特。有幾件事要提。如您所知，我們的監測抗體來自人類 - 由 Nils Lonberg 和他的同事（前 Medarex）開發的 [XeNa] 小鼠模型。所以我們有了完全人類抗體。它是一種 IgG4 抗體，鉸鏈區發生突變，與 IgG1 一致。其他人建議可能存在一些[ADC]。我們體外絕對沒有，臨床上我們也沒有看到。我認為研究這些抗體的免疫原性也很重要。我們的抗體是全人類抗體，在我們目前治療的近 1000 名患者中，我們發現其免疫原性非常低。我認為，正如您所提到的，[genocet] 抗體，這當然是一種 CDR 移植抗體，我認為它再次很重要。它有一個不同的目標，而不是免疫細胞。因此，應該仔細研究免疫原性。當然，衡量這一點的一個標準是你的劑量。正如我們剛才在上一個問題中提到的，我們的劑量較低，這反映了免疫原性較低。那麼讓我就此打住吧。

Great. Thanks, Seamus. Can, go to the next one, Kayla, please?

偉大的。謝謝，西莫。凱拉，可以轉到下一首嗎？

Chris Schott, JPMorgan.

克里斯·肖特，摩根大通。

Great. Thanks very much. Just a couple questions, to shift gears a bit to diabetes. For Onglyza, it looks like we've seen a little bit of share loss. How are you thinking about that and addressing that share dynamic? Second question -- on Bydureon, we are seeing some gradual uptake. But given the additional resources you put on the product, are you where you want to at this point with that launch, or relaunch profile? And then finally, just when we look at the mid-stage pipeline beyond PD-1, we'd love to hear, in terms of what you're most excited about with the rest of the portfolio. Maybe Elliott, since this is one of the last earnings calls we will have you on? So any comments there would be appreciated. Thanks.

偉大的。非常感謝。只是幾個問題，稍微轉向一下糖尿病。對於 Onglyza 來說，我們似乎看到了一些份額的損失。您如何看待這一問題並解決這一共享動態？第二個問題——在 Bydureon 上，我們看到一些逐漸被採用。但是考慮到您在產品上投入的額外資源，您現在是否希望發布或重新啟動配置文件？最後，當我們審視 PD-1 之外的中期研發管線時，我們很想听聽您對產品組合的其餘部分最感興趣的是什麼。也許埃利奧特（Elliott），因為這是我們邀請您參加的最後一次財報電話會議之一？因此，如有任何意見，我們將不勝感激。謝謝。

Yes, this is Giovanni. Let me comment on the diabetes portfolio performance in the US. First, going back to the comments made by Charlie at the beginning of the call, over the last two quarters in the US, we have fundamentally transformed our commercial organization. We have integrated the AZ and Bristol-Myers Squibb teams. We have realigned, restructured, and increased the sales of our sales -- the size of our sales organizations. And that transition has been completed at the end of the first quarter. And we acknowledge that during this period of transition, in a very competitive market we have seen some disruption to our commercial effort.

是的，這是喬瓦尼。讓我評論一下美國糖尿病投資組合的表現。首先，回到查理在電話會議開始時發表的評論，在美國過去兩個季度，我們從根本上改變了我們的商業組織。我們整合了 AZ 和百時美施貴寶團隊。我們重新調整、重組並增加了銷售部門的銷售額——銷售組織的規模。這一過渡已於第一季度末完成。我們承認，在這個過渡時期，在競爭非常激烈的市場中，我們的商業努力受到了一些干擾。

Now on Q2 and beyond, that transition is behind us. Our teams are fully staffed. We have the right level of resourcing, and our teams are back in the market promoting the full portfolio of products. With respect to Onglyza, you will remember that Onglyza grew very rapidly, increased its market share, and had very strong performance in 2012. In the first quarter of 2013, we have seen a flattening of our TRX share and some loss of our MBRX share, which is really related to the factors I described before. But also, to the fact that the DPP-4 market growth slowed down considerably, and clearly, the competitive pressure in this segment increased. We have seen a flattening of our share in March and April. And I think that is a positive indicator, and we are really focused on returning to growth during the remainder of 2013.

現在，在第二季度及以後，這種轉變已經過去了。我們的團隊人員齊全。我們擁有適當的資源水平，我們的團隊重新回到市場推廣完整的產品組合。說到Onglyza，大家一定記得，2012年，Onglyza增長非常迅速，市場份額不斷增加，業績非常強勁。2013年第一季度，我們看到TRX份額趨於平緩，MBRX份額有所下降，這確實與我之前描述的因素有關。但事實上，DPP-4 市場增長大幅放緩，顯然該領域的競爭壓力有所增加。我們看到三月和四月的份額趨於平緩。我認為這是一個積極的指標，我們真正專注於在 2013 年剩餘時間內恢復增長。

With respect to Bydureon, when we started promoting Bydureon, we had set three objectives for us as we started promoting this franchise. The first one was to improve access for Bydureon. The second one was to broaden the prescriber base, particularly in primary care. And the third one, clearly, was to accelerate in the development of the dual chamber pen and bring that to market. So, we have made progress in all of those areas. Access for Bydureon has improved in both the commercial and the Medicare space. We have actually grown significantly the prescriber base, particularly in primary care.

關於 Bydureon，當我們開始推廣 Bydureon 時，我們在開始推廣該系列產品時設定了三個目標。第一個是改善 Bydureon 的訪問。第二個是擴大處方者基礎，特別是在初級保健領域。第三個目標顯然是加速雙室筆的開發並將其推向市場。因此，我們在所有這些領域都取得了進展。Bydureon 在商業和醫療保險領域的使用情況都得到了改善。實際上，我們的處方者基礎顯著增長，特別是在初級保健領域。

And we are on track to launch the dual chamber pen, which is an important driver of incremental growth at the beginning of 2014. As a result of that, we have seen growth for Bydureon in terms of TRX, as we grew 18% in Q1 versus the last quarter of 2012. We also increased two share points in the market, and as a leading indicator, our MBRX growth has been stronger than that. So, we clearly believe Bydureon can grow more and faster. And as I said at the beginning, we have the right teams and resources in place to continue to drive that growth. I should also, say thinking about the Exenatide franchise, that we believe there continues to be good opportunities for Byetta. And as of the beginning of Q2, we have actually increased the resourcing behind promoting Byetta in combination with short-acting insulin.

我們即將推出雙室筆，這是 2014 年初增量增長的重要推動力。因此，我們看到 Bydureon 的 TRX 有所增長，第一季度與 2012 年最後一個季度相比增長了 18%。我們還增加了兩個市場份額，作為領先指標，我們的 MBRX 增長比這更強勁。因此，我們堅信 Bydureon 能夠增長得更多、更快。正如我在一開始所說的，我們擁有合適的團隊和資源來繼續推動這一增長。我還應該說，考慮到艾塞那肽特許經營權，我們相信 Byetta 仍然有很好的機會。截至第二季度初，我們實際上增加了推廣 Byetta 與短效胰島素組合的資源。

Chris this is Elliott. As I have said before, I have been privileged to lead this R&D organization through a very important transformation. And my last act has been focused on a very efficient transition, so that the great momentum that you are sensing continues. And I believe in Francis Cuss, we have the leader to effect that important transition. And we have a team that supports him that is responsible for how far we have come. I'm very excited about the timing here, because not only the leadership, but the timing of me leaving, coincides with a great deal of momentum and catalyst, not only in the late stage, but moving from discovery into the mid stage. And Francis has been the leader in charge of that, and should comment on some of the exciting things that we both see.

克里斯，這是埃利奧特。正如我之前所說，我很榮幸能夠領導這個研發組織經歷一次非常重要的轉型。我的最後一幕專注於非常有效的過渡，以便你們感受到的巨大勢頭得以延續。我相信弗朗西斯·庫斯，我們有領導者來實現這一重要的過渡。我們有一支支持他的團隊，他們對我們取得的進步負有責任。我對這裡的時機感到非常興奮，因為不僅是領導層，而且是我離開的時機，都伴隨著巨大的動力和催化劑，不僅在後期，而且從發現階段進入中期階段。弗朗西斯一直是負責這件事的領導者，他應該對我們都看到的一些令人興奮的事情發表評論。

Thanks, Elliott. So, we have talked just a month ago about our excitement around Nivolumab. But I think it's important to realize that we have an immunoncology platform, and I find it incredibly exciting that we actually have seven immunoncology assets now between early and full development. We've got more than a dozen back in discovery.

謝謝，埃利奧特。所以，就在一個月前，我們剛剛談論了我們對納武單抗的興奮。但我認為重要的是要認識到我們擁有一個免疫腫瘤學平台，而且我發現令人難以置信的是，我們現在實際上擁有七個處於早期開發和全面開發階段的免疫腫瘤學資產。我們已經發現了十多個。

And we have put together an integrated, hypothesis-driven kind of combination strategy. You will see the first fruits of that at ASCO, when we present some preliminary data on the Ipilimumab-Nivolumab combination. But there is a number of other combination trials ongoing in early clinical research. And we have a translational -- global translational immunoncology network where we have -- we are partnering with academics around the world to help us develop models and develop clinical data to help us bring forward, what we believe will be the flowering of IO, which is in combination therapy, which will allow us to continue providing transformative clinical benefit to patients.

我們制定了一種綜合的、假設驅動的組合策略。當我們在 ASCO 上展示 Ipilimumab-Nivolumab 組合的一些初步數據時，您將看到第一批成果。但早期臨床研究中正在進行許多其他組合試驗。我們擁有一個全球轉化免疫學網絡，我們正在與世界各地的學者合作，幫助我們開發模型並開發臨床數據，以幫助我們推進，我們相信這將是 IO 的繁榮，正在進行聯合治療，這將使我們能夠繼續為患者提供變革性的臨床益處。

Thanks.

謝謝。

Thanks, Chris. Can we go to the next one, Kayla?

謝謝，克里斯。我們可以轉到下一個嗎，凱拉？

Gregg Gilbert, Bank of America.

格雷格·吉爾伯特，美國銀行。

Thanks. First, for Elliott and Francis. I'm not sure if you answered whether you asked for breakthrough status or not. My real question, though is on SGLT2. Given your knowledge of your program, and having seen an ad come, as well as label approved for another drug in the class, is it fair to say that there can be some meaningful differentiation among the players in this class? And then for Charlie, I was curious if you're considering any deals that are larger than the typical string of pearls kind of deals you have done in the past? And what would a larger deal have to bring to the table to be seriously considered? Thanks.

謝謝。首先是埃利奧特和弗朗西斯。我不確定你是否回答了是否要求突破狀態。不過，我真正的問題是關於 SGLT2。鑑於您對您的計劃的了解，並且看到了廣告，以及該類別中另一種藥物的批准標籤，是否可以公平地說該類別中的參與者之間可能存在一些有意義的差異？然後，對於查理，我很好奇您是否正在考慮任何比您過去做過的典型珍珠串交易規模更大的交易？更大的交易必須提交哪些內容才能得到認真考慮？謝謝。

Yes, Greg. This is Elliott. I'll just repeat, what we are seeing is that we have breakthrough therapy in HCB. We do not have breakthrough therapy on PD-1. We utilized a different mechanism that provides, we think, the same kind of advantage to get to the advanced stage we are at. With regard to Forxiga, we believe that it's good for the SGLT2 field to not have, not only our first-in-class molecule approved in Europe and things progressing well there, but the US FDA division recognizing the mechanism by the approval of a competitor. We will be submitting mid year our submission with even stronger data on the benefits side, and I believe all the questions of safety addressed. And I do believe these will be important members of arma-mentarium, and that we see differentiation.

是的，格雷格。這是埃利奧特。我重複一遍，我們所看到的是 HCB 療法取得了突破性進展。我們還沒有針對 PD-1 的突破性療法。我們認為，我們利用了一種不同的機制，它提供了同樣的優勢來進入我們目前所處的高級階段。關於 Forxiga，我們認為，對於 SGLT2 領域來說，不僅我們的一流分子在歐洲獲得批准並且進展順利，而且美國 FDA 部門通過競爭對手的批准來認可該機制，這對 SGLT2 領域來說是件好事。我們將在年中提交我們的意見書，其中包含有關效益方面更強有力的數據，我相信所有安全問題都已得到解決。我確實相信這些將成為武器裝備的重要成員，並且我們看到了差異化。

Let me just quickly talk on business development. We have always said that it an important component of our balanced approach to capital allocation, and it has to pass three hurdles. It has to pass strategically, because it makes sense for Bristol-Myers Squibb. Does the science hold up, and does it make financial sense for us? And we have said all along we are agnostic around deal size. But if you look back retrospectively around our string of pearls, you can see the type of deals that we have done.

我簡單談一下業務發展。我們一直說，這是我們平衡資本配置的重要組成部分，它必須經過三個障礙。它必須戰略性地通過，因為它對百時美施貴寶來說有意義。科學是否站得住腳？它對我們有經濟意義嗎？我們一直說過，我們對交易規模持不可知論。但如果你回顧一下我們的珍珠鍊，你就會看到我們所做的交易類型。

Great. Thanks, Greg. Can we go to the next question, please, Kayla?

偉大的。謝謝，格雷格。凱拉，我們可以進入下一個問題嗎？

Mark Schoenebaum, ISI Group.

馬克·舍內鮑姆，ISI 集團。

Hey Elliott, maybe I can ask you something. This has been brought up before, but I would really love to get your update and complete thoughts on this. And I know all the dialogue on this at ASCO, as well. But why shouldn't it be our base case expectation, as investors, that the use of your anti-PD-1 antibody is likely, although certainly not assured, but likely to be restricted to patients with PD-L1 expression, given the fact there have been zero recessed responses, at least, in those patients. Thank you very much.

嘿艾略特，也許我可以問你一些事情。之前已經提出過這個問題，但我真的很想了解您對此的更新和完整想法。我也知道 ASCO 上有關此問題的所有對話。但是，作為投資者，我們的基本案例期望為什麼不應該是，您的抗 PD-1 抗體的使用很可能（儘管肯定不能保證）但很可能僅限於具有 PD-L1 表達的患者，因為事實上至少在這些患者中，隱性反應為零。非常感謝。

It is Francis. Let me take that one, Mark. So it is just not true, actually, that we have not seen responses in patients without PD-L1. There may be several reasons for this. One may be we just don't understand the mechanism well enough. It is true, and you can look back at our data last year, that there was a higher response rate in the PD-L1 patients. But it wasn't exclusively so, and it has continued to be the case here.

這是弗朗西斯.讓我來拿那個，馬克。因此，事實上，我們尚未在沒有 PD-L1 的患者中看到反應，這是不正確的。這可能有幾個原因。其一可能是我們對這一機制還不夠了解。確實如此，你可以回顧一下我們去年的數據，PD-L1 患者的緩解率更高。但情況並非完全如此，而且這裡的情況仍然如此。

One of the particular issues, I think, with melanoma is that a sampling of the tumors might be very heterogeneous. You always run the risk of having a tumor which is apparently negative, but other tumors are positive. So we're taking the view that we're doing a very comprehensive Phase III, where we will be looking at patients with and without PD-L1. We will collect the data, we'll be able to make a submission, either based on a biomarker, or not on a biomarker. But, of course, our principle is we want to make this medicine, this potent medicine, available to as many patients as possible.

我認為，黑色素瘤的特殊問題之一是腫瘤樣本可能非常異質。您總是面臨患上表面呈陰性的腫瘤但其他腫瘤卻呈陽性的風險。因此，我們認為我們正在進行一項非常全面的 III 期臨床試驗，我們將研究攜帶和不攜帶 PD-L1 的患者。我們將收集數據，我們將能夠基於生物標記或不基於生物標記進行提交。但是，當然，我們的原則是我們希望讓盡可能多的患者能夠使用這種藥物，這種有效的藥物。

Thank you, Mark. Can we go to the next question, please?

謝謝你，馬克。我們可以進入下一個問題嗎？

Steve Scala, Cowen.

史蒂夫·斯卡拉，考恩。

Thank you. Is Savor already complete, and is the data in house? I think you said that you will have the data in June, but will we get the data in June? And is the full data still expected at ESC? This is a bit confusing, because I think clinicaltrials.gov says the trial ends in July. And in the past, I don't recall your prepared remarks highlighting Savor to the extent that you did today. So, I find this whole thing very interesting. One other question on Eliquis. Was there any pipeline fill in the sales number? Thank you.

謝謝。Savor 是否已完成？數據是否已在內部？我想你說你會在六月份得到數據，但是我們會在六月份得到數據嗎？ESC 仍有望提供完整數據嗎？這有點令人困惑，因為我認為 ClinicalTrials.gov 說試驗將於 7 月結束。過去，我不記得您準備好的講話中像今天這樣強調“品味”。所以，我覺得整件事非常有趣。關於 Eliquis 的另一個問題。銷售數量是否有管道填寫？謝謝。

Thanks, Steve. This is John, real quick. In terms of whether or not -- what the disclosure on Savor will be, I don't think it's really -- we're ready to comment on that. We will have to work through that once we see the data with AstraZeneca. Elliott, do you want to --? Anything else?

謝謝，史蒂夫。這是約翰，速度真快。至於是否——Savor 的披露內容是什麼，我認為不是——我們準備對此發表評論。一旦我們看到阿斯利康的數據，我們就必須解決這個問題。艾略特，你想——嗎？還要別的嗎？

Well, Steve always asks me this, and this is the last time I can answer. No, I haven't seen the data. And we expect to be looking at it sometime in the summer. I'm not exactly sure when the events will be completed. Maybe there was confusion, because we can't say exactly what meeting we will present -- be able to present at, but we certainly want to present towards the end of the year, and the meeting that you mentioned would be the likely target.

好吧，史蒂夫總是問我這個問題，這是我最後一次回答。不，我還沒有看到數據。我們預計會在夏天的某個時候進行研究。我不太確定活動何時完成。也許有些困惑，因為我們不能確切地說我們將在什麼會議上進行演示——能夠在哪些會議上進行演示，但我們當然希望在年底前進行演示，而您提到的會議將是可能的目標。

And on Eliquis, Steve, the best way, again, to look at performance is to look at the development TRXs in the US. Obviously, with the launch of any product in the US, there is a distribution to the channel, and that was the case with Eliquis, as well, at the beginning.

關於 Eliquis，Steve，再次強調，觀察性能的最佳方法是觀察美國的 TRX 開發情況。顯然，任何產品在美國推出，都會有渠道分銷，Eliquis 一開始也是如此。

And, Steve, it was approximately $11 million in the US. Although in Japan, we were expecting in the broader GP arena, to have a little bit more stock, which we didn't. So there's a little bit of give and take there.

Steve，在美國的銷售額約為 1100 萬美元。儘管在日本，我們期望在更廣泛的大獎賽領域擁有更多的庫存，但我們沒有。所以這裡有一點給予和索取。

Thanks, Steve. Can we go to the next question, please?

謝謝，史蒂夫。我們可以進入下一個問題嗎？

David Risinger, Morgan Stanley.

大衛·瑞辛格，摩根士丹利。

Thanks very much. I have a couple questions. And first, I wanted to offer my congratulations to Francis. I haven't had a chance to do that yet. Congrats on your new role, Francis, and best of luck to you Elliott.

非常感謝。我有幾個問題。首先，我想向弗朗西斯表示祝賀。我還沒有機會這樣做。祝賀你擔任新角色，弗朗西斯，祝你好運，埃利奧特。

Thank you.

謝謝。

With respect to the DPP-4s and GLP-1s, can you comment on the upcoming cancer workshop, and how you see that, and what you think of the FDA's scrutiny of potential association with cancer risk? And then second, with respect to Dapagliflozin, and I guess this is more of a commercial question, but the way that AstraZeneca characterized the ramp in Germany was that the infection risk associated with Dapa isn't limiting uptake at all. That Dapa had ramped in the first ten weeks in Germany at a rate that was very similar to Januvia's launch. I guess my simple question is, do you think that the investment community is overly concerned about infection risk limiting the commercial uptake of Dapagliflozin? Thank you.

關於 DPP-4 和 GLP-1，您能否對即將舉行的癌症研討會發表評論？您對此有何看法，以及您對 FDA 對與癌症風險的潛在關聯的審查有何看法？其次，關於達格列淨，我想這更多的是一個商業問題，但阿斯利康描述德國市場增長的方式是，與達格列淨相關的感染風險根本不限制其使用。Dapa 在德國的前十週內的增長速度與 Januvia 的推出非常相似。我想我的簡單問題是，您是否認為投資界過度擔心感染風險限制了達格列淨的商業應用？謝謝。

I will answer first about Forxiga in Germany and actually, in Europe, where we are very pleased about what we are currently seeing. We are off to a very good start in the markets where we have launched. If we look at Germany specifically, the feedback we get from the physician and from the patient are extremely encouraging. So what you have from (inaudible), we concur with. When we talk about the placebo side effect, what we hear from our physician and the patient is that they are manageable.

我將首先回答有關德國乃至歐洲的 Forxiga 的問題，我們對目前所看到的情況感到非常滿意。我們在已推出的市場上取得了良好的開端。如果我們具體看看德國，我們從醫生和患者那裡得到的反饋是非常令人鼓舞的。因此，我們同意您從（聽不清）中得到的信息。當我們談論安慰劑的副作用時，我們從醫生和患者那裡聽到的是，這些副作用是可以控制的。

We haven't seen any issues with the uptake linked to the side effect profile. On the contrary, what we are hearing, and again, it's very early and anecdotally, is that the patient and the physician are satisfied with the profile, both in terms of the 1c reduction, but also with the additional benefit of weight loss and blood pressure. And actually, the weight loss comments we hear it that it has happened, it's a fast onset, so within the first month, the patient are coming back and making the comments to their physicians. Very strong first customer experience, which we understand is the base for the relatively happy update. Now, again, it is early days. We also know that the [pathologies] are particularly happy with the mode of action, which is differentiated and offer a new alternative. In addition, in monotherapy, as well as in combination, where we see the source of business as a non-insulin-dependent mechanism.

我們還沒有發現任何與副作用相關的吸收問題。相反，我們所聽到的，而且，這是非常早期和軼事性的，是患者和醫生對概況感到滿意，無論是在 1c 減少方面，還是在減肥和血液方面的額外好處壓力。事實上，我們聽到的減肥評論說它已經發生了，它起效很快，所以在第一個月內，病人就會回來並向他們的醫生提出評論。非常強大的首次客戶體驗，我們知道這是相對愉快的更新的基礎。現在，再說一次，現在還為時尚早。我們還知道，[病理學]對這種差異化的作用方式特別滿意，並提供了一種新的選擇。此外，在單一療法以及聯合療法中，我們將業務來源視為非胰島素依賴機制。

Thank you very much, David, and thank you for your best wishes. Let me say a word about this whole area. There is pancreatitis, of course, and pancreatic carcinoma. And as you well know, ever since the GLP-1s and the DPP-4 inhibitors came out, there have been reports to the FDA of patients who develop pancreatitis. While treated with these patients, of course, these patients are at risk anyway of pancreatitis. And, of course, all the agents that are both GLP-1 and DPP-4 actually carry the warnings about pancreatitis, which, of course, are reflection of these reports. I think it is always important to say these reports are regarded as hypothesis-generating because of the way they are collected, and they're not hypothesis-confirming.

非常感謝你，大衛，也感謝你的良好祝愿。讓我談談整個領域。當然，還有胰腺炎和胰腺癌。眾所周知，自從 GLP-1 和 DPP-4 抑製劑問世以來，FDA 就不斷收到患者罹患胰腺炎的報告。當然，在接受這些患者治療時，這些患者無論如何都面臨著胰腺炎的風險。當然，所有 GLP-1 和 DPP-4 製劑實際上都帶有有關胰腺炎的警告，這當然反映了這些報告。我認為重要的是要說這些報告因其收集方式而被視為假設生成，而不是假設確認。

And I must say, we have no evidence from either our nonclinical or clinical sources to support a causal relationship between pancreatitis -- between the treatment with these medicines and pancreatitis. And, of course, we have done the exhaustive animal toxicology using the standard techniques. And we have seen nothing either with Onglyza or Byetta or Bydureon. In particular, there is no increased pancreatitis observed in randomized clinical trials. And a number of observation studies in healthcare databases have also demonstrated no effect. So, taken together, based on all of this, we, together with our partner, AZ of course, are very confident of the positive risk-benefit profile of the drug. And I think we are interested to hear what the science, when it is reviewed, because we know that other sponsors of these medicines have the same results that we have, that we can find no causal link. So we are looking forward to that scientific discussion.

我必須說，我們沒有來自非臨床或臨床來源的證據來支持胰腺炎之間——這些藥物的治療與胰腺炎之間存在因果關係。當然，我們已經使用標準技術進行了詳盡的動物毒理學研究。我們還沒有看到 Onglyza、Byetta 或 Bydureon 的任何消息。特別是，隨機臨床試驗中沒有觀察到胰腺炎增加。醫療保健數據庫中的一些觀察研究也表明沒有效果。因此，綜上所述，基於所有這些，我們當然與我們的合作夥伴 AZ 一起對該藥物的積極風險收益狀況非常有信心。我認為我們有興趣了解科學性，當它被審查時，因為我們知道這些藥物的其他贊助商也有與我們相同的結果，我們找不到因果關係。因此，我們期待著這種科學討論。

Just a comment on pancreatic carcinoma. It is very similar. We find no link, either in our animal studies, and, of course, we have done carcinogenicity studies in rodents for two years. We see nothing there or in the clinical studies. And I will comment a recent paper which, or course, stirred up some discussion on this from Butler and colleagues. We find this actually quite difficult to interpret and there is significant limitations around their -- both their link with the animal studies and, of course, with the way they have used their patient groups. We're going to be presenting some data. I believe, at this FDA meeting, and so we look forward to seeing the science review. Thanks very much.

只是對胰腺癌的評論。非常相似。我們在動物研究中也沒有發現任何联系，當然，我們已經在囓齒類動物中進行了兩年的致癌性研究。我們在那里或臨床研究中沒有看到任何結果。我將評論最近的一篇論文，或者說，該論文激起了巴特勒和同事對此的一些討論。我們發現這實際上很難解釋，而且它們與動物研究的聯繫，當然還有他們使用患者群體的方式，都存在很大的局限性。我們將提供一些數據。我相信，在這次 FDA 會議上，我們期待看到科學審查。非常感謝。

Thanks, David. Kayla, can we go to the next question, please?

謝謝，大衛。凱拉，我們可以進入下一個問題嗎？

Marc Goodman, UBS.

馬克·古德曼，瑞銀集團。

Couple of questions. First, Lilly yesterday mentioned that there was some extra costs in their business due to the donut hole, and I was curious whether that was looking like it was going to be more of a hit this year than you thought it was going to be when you started the year? Second, on Orencia, can you talk about whether that product has been impacted at all by the new launch of Xeljanz, and if there was any stocking, or whatever? I know you mentioned something in your prepared remarks, but I missed it, of $36 million. I didn't hear exactly what that was.

有幾個問題。首先，禮來公司昨天提到，由於甜甜圈洞，他們的業務產生了一些額外成本，我很好奇，今年這是否會比你想像的更受歡迎。今年開始？其次，關於 Orencia，您能否談談該產品是否受到新推出的 Xeljanz 的影響，以及是否有庫存或其他什麼？我知道您在準備好的發言中提到了 3600 萬美元，但我沒有註意到。我沒聽清楚那是什麼。

And then third, you talked about the DPP-4 class. We have all seen it slow down. I was curious if you had a hypothesis towards why? Is it just a law of big numbers? Thanks.

第三，你談到了 DPP-4 級。我們都看到它放緩了。我很好奇你是否對原因有一個假設？這只是大數定律嗎？謝謝。

Marc, thanks for your questions. In regard to the donut hole, the donut hole costs are really a reflection of the portfolio. That depends upon the product and which ones are taken by Medicare patients. We haven't really seen anything different from our original plans. I can't comment on beyond that. In regard to the Medicaid reversal of the $36 million, that relates to, as states continue to provide us with the billing, we've reviewed that vis-à-vis our accruals and assumptions that we made when we originally established them. So it's just basically a true-up of some of our prior-year accruals.

馬克，謝謝你的提問。關於甜甜圈洞，甜甜圈洞成本實際上反映了投資組合。這取決於產品以及 Medicare 患者服用的產品。我們還沒有看到與最初計劃有任何不同的地方。除此之外我無法發表評論。關於 3600 萬美元的醫療補助逆轉，這與各州繼續向我們提供賬單有關，我們已經根據我們最初確定的應計項目和假設進行了審查。所以這基本上是我們上一年的一些應計項目的真實情況。

Let me -- this is Giovanni. Let me make a couple of comments. First on the performance of Orencia. We had very strong performance of Orencia in the US in Q1,with significant growth of 25% over prior year. That was driven by the successful launch of Sub[QU], which generated significant growth in 2012. It is early to fully assess the impact of the launch of Xeljanz. We have seen some increase in share, primarily in the switch market, which has had an impact on all players in the subcutaneous market, but the impact on us, specifically, has been very modest. And we're very pleased that we have become the third most prescribed Sub[QU] agent in the US market.

讓我——這是喬瓦尼。讓我發表幾點評論。首先是奧倫西亞的表現。第一季度，Orencia 在美國的表現非常強勁，比去年同期大幅增長 25%。這是由 Sub[QU] 的成功推出推動的，該產品在 2012 年實現了顯著增長。現在全面評估 Xeljanz 上市的影響還為時過早。我們看到份額有所增加，主要是在開關市場，這對皮下市場的所有參與者都產生了影響，但具體對我們的影響非常有限。我們非常高興我們已成為美國市場上處方量第三大的 Sub[QU] 藥物。

With respect to your comments on the growth of DPP-4's slowing down, there may actually be a number of different factors impacting that. As reminder, the only comment I would make is part of the accelerated growth that we had seen in 2012 was linked to the significant decrease in the TZD market with the entry of generics in that area. So there has been a transition of prescription from one class to the other. The growth has slowed down, but it continues to be healthy.

關於您對 DPP-4 增長放緩的評論，實際上可能有許多不同的因素對其產生影響。提醒一下，我唯一要評論的是，我們在 2012 年看到的加速增長與 TZD 市場隨著仿製藥進入該領域而大幅下降有關。因此，處方已經從一類過渡到另一類。增長速度有所放緩，但仍然保持健康。

Thanks, Marc. Kayla, I think we have time for two more questions.

謝謝，馬克。凱拉，我想我們還有時間問兩個問題。

Andrew Baum, Citi.

安德魯·鮑姆，花旗銀行。

Andrew?

安德魯？

Andrew Baum, your line is open.

安德魯·鮑姆，您的線路已接通。

Okay, we can move on, Kayla.

好的，我們可以繼續了，凱拉。

Alex Arfaei, BMO Capital Markets.

Alex Arfaei，BMO 資本市場。

Good morning. Thank you for taking the question. Following up on your comments regarding the growth of Bydureon on the SLGT-2s, I was wondering how you see this market evolving? Specifically, do you see the SGLT-2s being used ahead of the GLP-1s on par with DPP-4s? If you could talk about how you plan to position your diabetes products?

早上好。感謝您提出問題。繼您對 SLGT-2 上 Bydureon 的增長發表評論之後，我想知道您如何看待這個市場的發展？具體來說，您是否認為 SGLT-2 在 GLP-1 之前使用，與 DPP-4 同等？您能談談您打算如何定位您的糖尿病產品嗎？

And a follow-up, if I may? My understanding is that you have closed the Amylin site in San Diego and there have been significant headcount reductions regarding their advised agreement for Abilify. Are there any major opportunities for cost savings as the Eliquis launch ramps up? Thank you.

如果可以的話，還有後續行動嗎？我的理解是，你們已經關閉了位於聖地亞哥的 Amylin 工廠，並且根據 Abilify 的建議協議，人員數量大幅減少。隨著 Eliquis 上市的加快，是否存在節省成本的重大機會？謝謝。

Let me comment on Amylin. When we initially purchased Amylin, we assumed in real terms and in our guidance that we gave, that there would be certain synergies related to that acquisition. The San Diego -- the overall cost opportunity was already reflected in the guidance that we have provided.

讓我評論一下胰淀素。當我們最初購買 Amylin 時，我們根據實際情況和我們提供的指導假設，此次收購將會產生一定的協同效應。聖地亞哥——總體成本機會已經反映在我們提供的指導中。

So, you were asking the question about how to think about SGLT-2 and GLP-1. What we are looking at the global market, and then we may want to comment about the US, is that, depending also on the final labels and the access obtained by those class of products, we may end up having very different due dates. So that's one. However, from the scientific standpoint, we clearly believe that with the SGLT-1 provide a good alternative for patient that have a need of a product that will combine the -- with benefit a 1c, as well as benefit on blood pressure and weight loss. So, clearly in that space of the physician and patient that will agree on an oral treatment over the long term, SLGT-1 [ever place].

所以，您問的是如何看待 SGLT-2 和 GLP-1 的問題。我們正在關注全球市場，然後我們可能想對美國發表評論，那就是，根據最終標籤和這些類別產品獲得的訪問權限，我們最終可能會有非常不同的截止日期。這就是其中之一。然而，從科學的角度來看，我們清楚地相信，SGLT-1 為需要一種產品的患者提供了一個很好的替代方案，該產品將具有 a 1c 的益處，以及對血壓和減肥的益處。因此，很明顯，在醫生和患者同意長期口服治療的領域，SLGT-1 [永遠存在]。

Now, when you look at the benefit of SGLT-1, especially when they can be used on a weekly basis, and potentially later on, on a monthly basis, that creates a very different set of opportunities. And when we look at behaviors of patient, you find clearly a space prior to insulin, but you also find a space in a number patient that do not want treatment every day. So, there are different patient profile. We think that we will be able, having the chance of the (inaudible) portfolio, to combine the optimal benefit for the Company and for the patient having the possibility to play in those two area.

現在，當您看到 SGLT-1 的好處時，特別是當它們可以每週使用一次，甚至以後可能每月使用一次時，就會創造出一系列非常不同的機會。當我們觀察患者的行為時，您會清楚地發現胰島素之前有一個空間，但您也會在一些不想每天接受治療的患者中發現一個空間。因此，存在不同的患者概況。我們認為，通過（聽不清）投資組合的機會，我們將能夠將公司和有機會在這兩個領域發揮作用的患者的最佳利益結合起來。

Just to add something on GLP-1s in the US market. We see significant opportunity for continued growth of GLP-1s. They are currently prescribed to less than 10% of diabetes patients in the US, and they have been prescribed at the beginning primarily by endocrinologists. And in fact, the prescribers based at this point is much more narrow than you see with classes like DPP- 4s. The class is growing very rapidly. We believe that will continue, because with the ability of Bydureon as a weekly agent, the good efficacy, and the very good tolerability profile of Bydureon, there clearly is room for increased penetration in primary care. That is exactly what we are focusing on, and that is what we are beginning to see happen. So, we see continued potential for growth with GLP-1s.

只是為了在美國市場的 GLP-1 上添加一些內容。我們看到 GLP-1 持續增長的重大機會。目前，美國祇有不到 10% 的糖尿病患者開出此類藥物，而且一開始主要由內分泌科醫生開出處方。事實上，此時的處方者範圍比您在 DPP-4 等類別中看到的要窄得多。班級發展非常迅速。我們相信這種情況將會持續下去，因為憑藉 Bydureon 作為每週一次藥物的能力、良好的療效以及 Bydureon 非常好的耐受性，顯然在初級保健中的滲透率還有提高的空間。這正是我們所關注的，也是我們開始看到的。因此，我們看到 GLP-1 的持續增長潛力。

Great. Thanks very much, Alex. I think that's all the time we have. I appreciate everybody's joining us for the call this morning. And before we close, I would like to turn it back to Charlie for any closing comments.

偉大的。非常感謝，亞歷克斯。我想這就是我們所有的時間了。我感謝大家今天早上參加我們的電話會議。在我們結束之前，我想將其轉回查理以徵求結束意見。

Thanks, John. And thanks, everyone, for your questions. Again, our first quarter was a good start to an important year. One in which our focus is on commercial execution and delivery of our diversified pipeline. Thank you very much.

謝謝，約翰。謝謝大家提出的問題。同樣，我們的第一季度是重要一年的良好開端。其中我們的重點是多元化管道的商業執行和交付。非常感謝。

This concludes today's conference. Thank you for your participation.

今天的會議到此結束。感謝您的參與。