雷傑納榮製藥 (REGN) 2017 Q1 法說會逐字稿

Welcome to the Regeneron Pharmaceuticals First Quarter 2017 Earnings Conference Call. My name is Sylvia, and I'll be your operator for today's call. (Operator Instructions) Please note that this conference is being recorded.

歡迎參加 Regeneron Pharmaceuticals 2017 年第一季財報電話會議。我叫西爾維婭，我將擔任您今天通話的接線生。（操作員說明）請注意，本次會議正在錄音。

I will now turn the call over to Manisha Narasimhan. Manisha, you may begin.

現在我將把電話轉給瑪妮莎·納拉辛漢。瑪妮莎，你可以開始了。

Thank you, Sylvia. Good morning and welcome to Regeneron Pharmaceuticals First Quarter 2017 Conference Call. An archive of this webcast will be available on our website under Events and Presentations for 30 days.

謝謝你，西爾維亞。早安，歡迎參加 Regeneron Pharmaceuticals 2017 年第一季電話會議。本次網路直播的存檔將在我們網站的「活動與演示」欄位下保留 30 天。

Joining me on the call today are Dr. Leonard Schleifer, Founder, President and Chief Executive Officer; George Yancopoulos, Founding Scientist, President and Chief Scientific Officer; Bob Terifay, Executive Vice President Commercial; and Bob Landry, Chief Financial Officer. After our prepared remarks, we will open the call for Q&A.

今天與我一起參加電話會議的有：創辦人、總裁兼執行長 Leonard Schleifer 博士；創始科學家、總裁兼首席科學官 George Yancopoulos；商業執行副總裁 Bob Terifay；以及財務長 Bob Landry。在我們發言完畢後，我們將開放問答環節。

I would also like to remind you that remarks made on this call today include forward-looking statements about Regeneron. Such statements may include, but are not limited to, those related to Regeneron and its products and business, sales and expense forecasts, financial forecasts, development programs, collaborations, finances, regulatory matters, intellectual property and competition. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in such statements. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, or SEC, including its Form 10-Q for the quarter ended March 31, 2017, which was filed with the SEC this morning. Regeneron does not undertake any obligation to update publicly any forward-looking statement, whether as a result of new information, future events or otherwise.

我還要提醒各位，今天電話會議上發表的言論包含 Regeneron 的前瞻性陳述。此類聲明可能包括但不限於與 Regeneron 及其產品和業務、銷售和支出預測、財務預測、開發計劃、合作、財務、監管事項、智慧財產權和競爭相關的聲明。每項前瞻性聲明都存在風險和不確定性，可能導致實際結果和事件與此類聲明中預測的結果和事件有重大差異。有關這些及其他重大風險的更完整描述，請參閱 Regeneron 向美國證券交易委員會 (SEC) 提交的文件，包括其截至 2017 年 3 月 31 日的季度 10-Q 表格，該表格已於今天上午提交給 SEC。Regeneron公司不承擔任何公開更新任何前瞻性聲明的義務，無論是由於新資訊、未來事件或其他原因。

In addition, please note that GAAP and non-GAAP measures will be discussed on today's call. Information regarding our use of non-GAAP financial measures and a reconciliation of these measures to GAAP are available in our financial results press release, which can be accessed on our website at www.regeneron.com.

此外，請注意，今天的電話會議將討論GAAP和非GAAP指標。有關我們使用非公認會計準則財務指標的資訊以及這些指標與公認會計準則的調節表，請參閱我們的財務業績新聞稿，該新聞稿可在我們的網站 www.regeneron.com 上查閱。

Once our call concludes, Bob Landry and the IR team will be available to answer your questions. With that, let me turn the call over to our President and Chief Executive Officer, Dr. Len Schleifer.

通話結束後，鮑伯蘭德里和投資者關係團隊將回答您的問題。接下來，我將把電話交給我們的總裁兼執行長倫·施萊弗博士。

Thanks, Manisha. Good morning, everyone, and thank you for joining us on the call and webcast today. The first quarter of 2017 was an eventful and significant quarter. Dupixent, our breakthrough drug for the treatment of moderate-to-severe atopic dermatitis in adults, received regulatory approval in the United States and the launch is underway. This marked the first of 2 anticipated FDA approvals in 2017, the second being for sarilumab, also now known as Kevzara, where we have been granted an FDA action or PDUFA date of May 22.

謝謝你，瑪妮莎。各位早安，感謝大家今天參加我們的電話會議和網路直播。2017年第一季是個充滿事件且意義重大的季度。Dupixent 是我們治療成人中重度異位性皮膚炎的突破性藥物，已獲得美國監管部門批准，目前正在上市。這標誌著 2017 年預期的 2 項 FDA 批准中的第一項獲得通過，第二項是 sarilumab（現稱為 Kevzara），我們已獲得 FDA 批准或 PDUFA 日期為 5 月 22 日。

Before we get into the details of our quarterly performance, I want to take a moment to remind everyone of 2 important priorities at Regeneron. At the core, we have always been a company that is driven by science and committed to bringing important new drugs to patients in need. These priorities are directly responsible for the robust pipeline that we have today with 5 FDA-approved drugs and 16 product candidates in various stages of clinical development, all of which have come out of Regeneron Labs. George will provide more details on pipeline progress.

在我們詳細介紹季度業績之前，我想花一點時間提醒大家 Regeneron 的兩個重要優先事項。從本質上講，我們始終是一家以科學為驅動，致力於為有需要的患者帶來重要新藥的公司。這些優先事項直接促成了我們今天擁有的強大研發管線，其中包括 5 種 FDA 批准的藥物和 16 種處於不同臨床開發階段的候選產品，所有這些都來自 Regeneron Labs。喬治將提供更多關於管道建設進展的細節。

As we advance as a company the commercial aspect of our business has grown in importance as well. This year, we and our collaborator, Sanofi, are laser-focused on ensuring that the ongoing Dupixent launch is successful. While it is too early for us to provide you with sales updates, I am pleased to share with you that about 5 weeks into the launch of Dupixent, things are going -- continuing to go well. We are pleased with the interest and reception from both patients and physicians. Just last week, you heard from our partner, Sanofi, that about 4 weeks into the launch, more than 2,500 prescriptions for new patience for Dupixent had been written. I'm happy to inform you to date that over 3,500 new prescriptions have been written for Dupixent, which translates into over 900 prescriptions written in the past week. We are also pleased with the reaction from the payers on our responsible approach to pricing to date. We continue to work hard to ensure that eligible patients have access to the drug, and we are pleased with the coverage and utilization management criteria that have been put in place thus far. Bob Terifay will provide additional details.

隨著公司的發展，我們業務的商業方面也變得越來越重要。今年，我們和我們的合作夥伴賽諾菲將全力確保正在進行的 Dupixent 上市取得成功。雖然現在提供銷售更新還為時過早，但我很高興地告訴大家，Dupixent 上市大約 5 週後，一切進展順利，並且還在繼續順利進行。我們對病人和醫生們的關注和反應感到非常滿意。就在上週，我們的合作夥伴賽諾菲宣布，Dupixent上市約4週後，已為新患者開立了超過2500張處方。我很高興地通知大家，截至目前，Dupixent 的新處方已超過 3500 張，其中過去一周就開出了 900 多張處方。我們也對付款方迄今為止對我們負責任的定價方式的回饋感到滿意。我們繼續努力確保符合條件的患者能夠獲得該藥物，我們對目前已實施的覆蓋範圍和使用管理標準感到滿意。Bob Terifay將提供更多細節。

While atopic dermatitis in adults is a first indication, we are also investigating the use of Dupixent in several other indications and age groups, ranging for what we think could be a near-term opportunity in asthma to other indications such as nasal polyps and eosinophilic esophagitis. Just today, we reported our Phase II proof-of-concept study in eosinophilic esophagitis was positive. If we can get approval for these additional indications, we expect to be in launch mode with Dupixent for many years to come.

雖然成人異位性皮膚炎是首要適應症，但我們也在研究 Dupixent 在其他幾種適應症和年齡組中的應用，從我們認為近期可能在氣喘治療中出現的機會，到鼻息肉和嗜酸性食道炎等其他適應症。就在今天，我們宣布了我們在嗜酸性食道炎中的 II 期概念驗證研究結果為陽性。如果我們能夠獲得這些額外適應症的批准，我們預計 Dupixent 將在未來多年內保持上市狀態。

Maintaining our leadership position with EYLEA as the market-leading, branded anti-VEGF drug continues to be a key focus. With our first regulatory approval in wet age-related macular degeneration, or wet AMD, the EYLEA business was initially more concentrated towards the elderly, the majority of whom are Medicare patients. But with such approvals and indications such as diabetes macular edema, or DME; and diabetic retinopathy in DME; and retinal vein occlusion, we have diversified the patient groups where there is less reliance on Medicare.

保持 EYLEA 作為市場領先的品牌抗 VEGF 藥物的領先地位仍然是我們的重點。憑藉在濕性老年黃斑部病變（濕性 AMD）方面的首個監管批准，EYLEA 的業務最初更集中於老年人群體，其中大多數是 Medicare 患者。但隨著糖尿病性黃斑水腫（DME）、糖尿病性視網膜病變（DME）和視網膜靜脈阻塞等適應症的批准，我們擴大了患者群體，減少了他們對醫療保險的依賴。

We continue to support the ongoing launch of PRALUENT, our PCSK9 inhibitor antibody for lowering LDL cholesterol. We expect our 18,000-patient cardiovascular outcome study to be completed towards the end of the year with data in early 2018.

我們將繼續支持 PRALUENT 的持續上市，PRALUENT 是一種 PCSK9 抑制劑抗體，用於降低 LDL 膽固醇。我們預計這項涉及 18,000 名患者的心血管結果研究將於今年底完成，數據將於 2018 年初公佈。

On the U.S. patent litigation, we and our collaborator, Sanofi, have been granted an oral argument date of June 6, 2017, at the Court of Appeals for the Federal Circuit. Based on this timing, we could get a decision on the appeal before the end of the year.

關於美國專利訴訟，我們和我們的合作方賽諾菲已獲準於 2017 年 6 月 6 日在聯邦巡迴上訴法院進行口頭辯論。根據這個時間安排，我們預計在年底前得到上訴結果。

With that, I will now like to turn the call over to George.

接下來，我將把電話交給喬治。

Thank you, Len, and a very good morning to everyone has joined us today. On the call today, I would like to focus and our ongoing clinical development program for dupilumab, review some important data on the long-term use of EYLEA, share some updates on our immuno-oncology program, as well as the progress of the rest of our pipeline.

謝謝Len，也祝今天所有到場的朋友們早安。在今天的電話會議上，我想重點介紹我們正在進行的度普利尤單抗臨床開發項目，回顧一些關於 EYLEA 長期使用的重要數據，分享我們免疫腫瘤學項目的最新進展，以及我們其他研發管線的進展。

I'd like to begin with the approval of Dupixent, our IL-4/IL-13 blocker for the treatment of moderate-to-severe atopic dermatitis in adult patients whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. This approval was the culmination of a scientific quest that has been decades in the making. While Bob Terifay will address the ongoing launch of Dupixent into greater detail, I would like to focus on the progress that we are making in the clinical dupilumab in various other indications. Asthma is an important late-stage opportunity where we are investigating the use of dupilumab. Despite the recent approval of drugs from the IL-5 inhibitor class in what has been characterized as the allergic patient population. We believe there is an unmet medical need for these patients for a drug that can markedly improves lung function as well as provide further protection against exacerbations. In addition, there is a need for drugs that'll show efficacy in a wider patient population across all allergic classifications. Based on results from our Phase IIb pivotal study in asthma, where we showed robust improvements in both lung function, as measured by FEV1, and reductions in exacerbations in all patients regardless of their allergic classification, we believe that dupilumab has the potential, if approved, to fill these needs.

首先我想談談Dupixent的核准，這是一種IL-4/IL-13阻斷劑，用於治療中度至重度異位性皮膚炎成人患者，這些患者的病情無法透過局部處方療法得到充分控制，或者不宜採用這些療法。這項批准標誌著一項經過數十年科學探索的最終成果。Bob Terifay 將更詳細地介紹 Dupixent 的上市情況，而我想重點介紹我們在 dupilumab 臨床治療其他各種適應症方面取得的進展。氣喘是一個重要的後期治療機會，我們正在研究度普利尤單抗在該領域的應用。儘管最近 IL-5 抑制劑類藥物已獲批准用於治療過敏性患者族群。我們認為，這些患者迫切需要一種能夠顯著改善肺功能並進一步防止病情加重的藥物。此外，還需要研發能夠對所有過敏類型都有效的更廣泛患者群體的藥物。根據我們在氣喘 IIb 期關鍵性研究中獲得的結果，我們發現，無論患者的過敏分類如何，肺功能（以 FEV1 衡量）和病情加重次數均有顯著改善，我們相信，如果獲得批准，dupilumab 有潛力滿足這些需求。

Our second pivotal study in the adult asthma indication, the LIBERTY ASTHMA QUEST study, in patients with uncontrolled persistent asthma, is fully enrolled, and we continue to expect top line data later this year. We believe these data have the potential to confirm the broad efficacy we observed in the first pivotal study. If these data are positive, we expect to complete a regulatory submission in the United States in the fourth quarter of this year.

我們針對成人氣喘適應症的第二項關鍵研究—LIBERTY ASTHMA QUEST 研究，針對的是未控制的持續性氣喘患者，目前已完成全部入組，我們預計今年稍後將公佈初步數據。我們相信這些數據有可能證實我們在第一項關鍵研究中觀察到的廣泛療效。如果這些數據是正面的，我們預計今年第四季完成在美國的監管申報。

We also recently started enrolling patients in the Phase III study of dupilumab in pediatric asthma patients between the ages of 6 and 11 years in the second quarter of 2017. We're also evaluating dupilumab in pediatric atopic dermatitis, where there is a high unmet need and we were, again, granted breakthrough status by the FDA. Positive data from the open label Phase IIa trial in patients 6 to 17 years old with moderate-to-severe atopic dermatitis were recently presented at the American Academy of Dermatology Conference in March. The safety and efficacy data from this trial were very encouraging. We have initiated a Phase III study of dupilumab in adolescents between the ages of 12 to 17. We expect to initiate, in the second quarter of 2017, a second Phase III trial in pediatric patients between the ages of 6 and 11 years.

2017 年第二季度，我們開始招募 6 至 11 歲兒童氣喘患者參與度普利尤單抗 III 期研究。我們也正在評估度普利尤單抗在兒童異位性皮膚炎的應用，該領域存在著很高的未滿足需求，而且我們再次獲得了 FDA 的突破性療法認定。最近，在 3 月舉行的美國皮膚病學會會議上，公佈了針對 6 至 17 歲中重度異位性皮膚炎患者的開放標籤 IIa 期試驗的積極數據。這項試驗的安全性和有效性數據非常令人鼓舞。我們已啟動一項針對 12 至 17 歲青少年的 dupilumab III 期研究。我們預計將於 2017 年第二季啟動 6 至 11 歲兒科患者的第二項 III 期試驗。

We're also investigating dupilumab in a third clinical setting, which is the treatment of patients with nasal polyps. Following up on earlier positive data from our Phase II study in this population, we now have 2 separate Phase III studies that are currently enrolling patients. As Len mentioned, we recently obtained positive results in a Phase II proof-of-concept study of dupilumab in our fourth important clinical setting, which is in patients with active moderate-to-severe eosinophilic esophagitis, a chronic inflammation of the esophagus and one of the major causes of dysphagia, or difficulty in swallowing. In this Phase II study, we observed clinically meaningful efficacy for dupilumab as well as profound histologic and endoscopic improvement, together with the safety profile consistent with our previous clinical experience. Detailed data from this study will be presented in an upcoming medical conference. While eosinophilic esophagitis can be debilitating in adults, it is especially concerning in the pediatric population, where it can be a cause a failure to thrive, and this could potentially be an area of future clinical investigation to dupilumab. It is believed that eosinophilic esophagitis can be a manifestation of food allergies, further supporting the rationale of exploring the efficacy of dupilumab in patients suffering from severe specific food allergies. In the second half of 2017, we intend to initiate a Phase II study of dupilumab in patients with specific food allergy. The positive data for dupilumab across the 4 allergic or atopic conditions we have investigated to date, that is atopic dermatitis; asthma; nasal polyps; and now, eosinophilic esophagitis; is consistent with our long-standing hypotheses that this allergic condition -- that these allergic conditions reflect the same fundamental disease process, triggered by overactivity of the IL-4/IL-13 (inaudible). This unifying hypothesis suggest that the differences between these conditions largely reflect how overactivity of the IL-4/IL-13 pathway manifests differently in different tissues. For example, overactivity of IL-4 and IL-13 in the skin triggers atopic dermatitis; in the lower air way, it results in asthma; in the upper G.I. tract, it results in eosinophilic esophagitis. Unfortunate for many patients, IL-4/IL-13-driven allergies can manifest in multiple sites at the same time. Since dupilumab inhibits the key driver of this pathway in all these settings, we believe that it can represent a mechanism-based approach to treat the root cause of these allergic conditions rather than each individual indication on a separate basis. This represents a fundamentally new way to think of root and treat diseases previously and otherwise thought of as disparate and requiring distinct therapy. That is, mechanism-based treatment directed not by a diseased organ-specific manifestations by the -- but by the disease's fundamental cause and mechanism. We're also encouraged by the safety profile that we have observed thus far for dupilumab in these settings. I'd like to remind you that the current regulatory framework does not allow for mechanism-based approach of treatment but rather an indication-based approach. We are very interested in discussing this type of mechanism-based approach for treating allergic or atopic disease with the regulatory authorities while we continue to pursue more conventional approval strategies.

我們也在第三種臨床環境中研究度普利尤單抗，即治療鼻息肉患者。繼我們先前在該族群中進行的 II 期研究取得積極數據之後，我們現在有 2 項獨立的 III 期研究正在招募患者。正如 Len 所提到的，我們最近在第四個重要的臨床環境中，即患有活動性中度至重度嗜酸性食道炎（一種慢性食道炎症，也是吞嚥困難的主要原因之一）的患者中，dupilumab 的 II 期概念驗證研究取得了積極成果。在這項 II 期研究中，我們觀察到 dupilumab 具有臨床意義的療效，以及顯著的組織學和內視鏡改善，同時安全性與我們先前的臨床經驗一致。本研究的詳細數據將在即將召開的醫學會議上公佈。雖然嗜酸性食道炎對成年人來說可能很嚴重，但對兒童來說尤其令人擔憂，因為它可能導致兒童生長遲緩，而這可能是未來度普利尤單抗臨床研究的一個方向。人們認為嗜酸性食道炎可能是食物過敏的一種表現，這進一步支持了探索度普利尤單抗對患有嚴重特定食物過敏患者的療效的合理性。2017 年下半年，我們計劃啟動 dupilumab 治療特定食物過敏患者的 II 期研究。迄今為止，我們研究的 4 種過敏或異位性疾病（即異位性皮膚炎、氣喘、鼻息肉以及現在的嗜酸性食道炎）中，度普利尤單抗的積極數據與我們長期以來的假設一致，即這些過敏性疾病反映了相同的基本疾病過程，由 IL-4/IL-13 過度活躍引發（聽不清楚）。這個統一的假設表明，這些疾病之間的差異很大程度上反映了 IL-4/IL-13 路徑過度活躍在不同組織中表現不同的情況。例如，皮膚中 IL-4 和 IL-13 過度活躍會導致異位性皮膚炎；在下呼吸道中會導致氣喘；在上消化道中會導致嗜酸性食道炎。不幸的是，對於許多患者來說，IL-4/IL-13 驅動的過敏反應可能同時發生在多個部位。由於度普利尤單抗在所有這些情況下都能抑制該路徑的關鍵驅動因素，我們認為它可以代表一種基於機制的方法來治療這些過敏性疾病的根本原因，而不是單獨治療每種適應症。這代表了一種全新的思維方式，可以根除和治療以前被認為是截然不同且需要不同療法的疾病。也就是說，治療不是根據患病器官的具體表現來指導的，而是根據疾病的根本原因和機制來指導的。我們也對目前觀察到的度普利尤單抗在這些情況下的安全性感到鼓舞。我想提醒各位，目前的監管框架不允許基於機制的治療方法，而只能採用基於適應症的方法。我們非常有興趣與監管機構討論這種基於機制的過敏或特異性疾病治療方法，同時我們將繼續尋求更傳統的審批策略。

Turning now to Kevzara, our IL-6 receptor antibody for rheumatoid arthritis. As Len mentioned, we anticipate a regulatory decision in the United States, where we've been granted an FDA action date of May 22. In April of 2017, the European Medicines Agency's Committee for Medicinal Products for Human Use, or CHMP, adopted a positive opinion for Kevzara for the treatment of moderate-to-severe RA in adults. We expect the potential approval in Europe for Kevzara in the second quarter of 2017. We have also made regulatory submissions for Kevzara in Japan. Beyond RA, we are currently enrolling patients to the Phase II clinical study of sarilumab for the treatment of polyarticular-course juvenile idiopathic arthritis. We're also considering and investigating the use of sarilumab in other indications.

接下來我們來談談 Kevzara，這是一種用於治療類風濕性關節炎的 IL-6 受體抗體。正如 Len 所提到的，我們預計美國監管機構會做出決定，FDA 已授予我們 5 月 22 日的審批日期。2017 年 4 月，歐洲藥品管理局人用藥物委員會 (CHMP) 對 Kevzara 用於治療成人中度至重度類風濕性關節炎 (RA) 給予了正面評價。我們預計 Kevzara 將於 2017 年第二季在歐洲獲得批准。我們也向日本監管機構提交了 Kevzara 的相關申請。除了 RA 之外，我們目前正在招募患者參與 sarilumab 治療多關節型幼年特發性關節炎的 II 期臨床研究。我們也在考慮和研究 sarilumab 在其他適應症的應用。

Turning to our other late-stage programs, I'd like to begin with EYLEA. As Len mentioned, we are committed to maintaining our leadership position in bringing important advances to patients with the retinal diseases. To that end, we are conducting 2 Phase II studies of EYLEA in combination with nesvacumab, our antibody to ANG2, one in diabetic macular edema, our DME; and another in neovascular age-related macular degeneration, or wet AMD. Both studies are fully enrolled and we will evaluate efficacy and safety at 36 weeks, which we expect in the second half of this year. In addition, we are also investing in EYLEA as a monotherapy and a Phase III study in patients with nonproliferative diabetic retinopathy without diabetic macular edema. This study, called Panorama, continues to enroll patients.

接下來，我想談談我們其他後期項目，首先是EYLEA項目。正如 Len 所提到的，我們致力於保持我們在為視網膜疾病患者帶來重要進展方面的領先地位。為此，我們正在進行 2 項 EYLEA 與 nesvacumab（我們的抗 ANG2 抗體）聯合治療的 II 期研究，一項針對糖尿病性黃斑水腫 (DME)，另一項針對新生血管性老年性黃斑部病變 (濕性 AMD)。兩項研究均已完成招募，我們將於今年下半年（36 週）評估療效和安全性。此外，我們也正在投資 EYLEA 作為單藥療法，並進行針對非增殖性糖尿病視網膜病變（無糖尿病黃斑水腫）患者的 III 期研究。這項名為「全景研究」的研究仍在繼續招募患者。

I'd like to spend a few moments focusing on findings from long-term follow-up of our Phase III VIEW 1 study of EYLEA in patients with wet AMD, which we recently published on Ophthalmology Retina. As background, existing long-term data with other anti-VEGF agents, most notably from the government-sponsored [CAT] study, has shown that early visual gains obtained with anti-VEGF agents were not maintained over time. In fact, by the fifth year patients had lost, on average, over 3 letters compared to their original baseline. Over 20% of patients have progressed to become legally blind by year 5. It had been postulated that this loss of vision is due to inexorable progression of the disease process itself over time, even in the face of anti-VEGF treatment. Others had raised the theory that the anti-VEGF agents themselves contribute to geographic atrophy attribute over time, and thus, to the subsequent visual loss. In marked contrast to the CAT study, long-term follow-up data from the VIEW 1 study, where patients were treated with fixed-interval EYLEA dosing and received EYLEA, on average, every 12 weeks in year 2 and every 8 weeks in year 3 and 4, show that the vision gains observed at the end of the first year were, on average, largely maintained at 4 years. These long-term results provide the first evidence that long-term treatment with anti-VEGF agents can maintain vision gains in patients with wet AMD. We think this is our very important findings for the field. These data support our long-standing view that regular, fixed-interval dosing regimens result in substantially better visual outcomes compared to PRN or treat-and-extend dosing regimens, which, over time, result in suboptimal visual acuity benefits and even in substantial visual loss. We think this is probably true regardless of the anti-VEGF agent being utilized. Although we saw that more than -- about 50% of the patients in the second year exploratory-treatment phase of our long-term trial received fix quarterly treatment and maintained their vision, we are more comfortable that the every-2-month regimen is likely to maintain vision over the long term, based on larger and long-term experience. With regards to convenience-based regimens, such as PRN and treat-and-extend approaches, we think they are lacking in convincing in long-term evidence for their ability to maintain vision over the long term.

我想花幾分鐘時間重點介紹我們最近在《眼科視網膜》雜誌上發表的針對濕性 AMD 患者的 EYLEA III 期 VIEW 1 研究的長期追蹤結果。作為背景，現有的其他抗 VEGF 藥物的長期數據，尤其是政府資助的 [CAT] 研究的數據表明，使用抗 VEGF 藥物獲得的早期視力改善無法長期維持。事實上，到第五年，患者的平均字母數比他們最初的基線水平下降了 3 個字母以上。超過 20% 的患者在 5 年內發展為法定盲人。有人推測，這種視力喪失是由於疾病本身隨著時間的推移而不可阻擋地發展所致，即使接受了抗 VEGF 治療也是如此。另一些人則提出了這樣的理論：抗 VEGF 藥物本身會隨著時間的推移導致地圖狀萎縮，導致隨後的視力喪失。與 CAT 研究形成鮮明對比的是，VIEW 1 研究的長期隨訪數據顯示，患者接受固定間隔的 EYLEA 給藥治療，平均而言，在第 2 年每 12 週接受一次 EYLEA 治療，在第 3 年和第 4 年每 8 週接受一次 EYLEA 治療，結果顯示，在第一年末觀察到基本 4 年後得以維持的平均視力。這些長期結果首次證明，長期使用抗 VEGF 藥物治療可以維持濕性 AMD 患者的視力改善。我們認為這是我們在該領域非常重要的發現。這些數據支持我們長期以來的觀點，即與按需用藥或治療延長用藥方案相比，規律的、固定間隔的用藥方案可帶來更好的視覺效果，而按需用藥或治療延長用藥方案隨著時間的推移，會導致視力改善效果不佳，甚至導致嚴重的視力喪失。我們認為，無論使用何種抗 VEGF 藥物，這很可能都是事實。雖然我們看到，在我們長期試驗的第二年探索性治療階段，超過 50% 的患者接受了固定的季度治療並保持了視力，但根據更大規模和更長期的經驗，我們更有信心每 2 個月一次的治療方案更有可能長期保持視力。對於按需治療和治療延長等以便利性為基礎的治療方案，我們認為缺乏令人信服的長期證據來證明其能夠長期維持視力。

With regards to this point, we think that doctors should be strongly cautioning their patients that choosing convenience-based dosing has a high risk of causing permanent vision loss for their patients. We think it is important that retinal specialists and public health officials begin to recognize the potential public health crisis that may be resulting from irregular dosing regimens that do not follow the FDA-recommended usage guidelines, and that the loss of vision that these protocols may be causing may be needlessly occurring in thousands of patients, leaving many irrevocably legally blind.

關於這一點，我們認為醫師應該強烈告誡患者，選擇方便用藥方式有很高的風險會導致患者永久性失明。我們認為，視網膜專家和公共衛生官員應該開始認識到，不遵循 FDA 推薦使用指南的不規則用藥方案可能會導致潛在的公共衛生危機，這些方案可能會導致成千上萬的患者出現不必要的視力喪失，使許多人永久失明。

Moving on to PRALUENT, our PCSK9 inhibitor antibody for lowering LDL cholesterol. We are pleased to announce that PRALUENT was recently approved in the 300-milligram, once-monthly dosing regimen. We expect to report top line data from the 18,000 patient ODYSSEY OUTCOMES study in the first quarter of 2018. Positive outcome data reported with PCSK9 inhibitors further support the hypothesis that lowering LDL cholesterol with the PCSK9 inhibitor can reduce cardiovascular risk. We look forward to sharing data from our study in early 2018.

接下來是 PRALUENT，我們用來降低 LDL 膽固醇的 PCSK9 抑制劑抗體。我們很高興地宣布，PRALUENT 最近獲準採用 300 毫克、每月一次的給藥方案。我們預計將於 2018 年第一季公佈 18,000 名患者的 ODYSSEY OUTCOMES 研究的主要數據。PCSK9 抑制劑的積極療效數據進一步支持了使用 PCSK9 抑制劑降低 LDL 膽固醇可以降低心血管風險的假設。我們期待在 2018 年初分享我們的研究數據。

In addition to our efforts with PRALUENT in cardiovascular disease, we are also developing evinacumab, our antibody or ANGPTL3, for the treatment of homozygous familial hypercholesterolemia, or homozygous FH. In March of 2017, we announced that the FDA granted evinacumab breakthrough designation status. Just a few weeks ago, we presented a positive data from a Phase II proof-of-concept study of evinacumab in patients with homozygous FH. These data showed that patients, who normally don't respond well to statins or to PCSK9, experienced an average reduction of 50% in their LDL cholesterol following 2 subcutaneous injections of evinacumab, with an acceptable safety profile.

除了我們在心血管疾病領域與 PRALUENT 開展合作外，我們還在開發 evinacumab（我們的抗體或 ANGPTL3），用於治療純合子家族性高膽固醇血症（或純合子 FH）。2017 年 3 月，我們宣布 FDA 授予 evinacumab 突破性療法認定。就在幾週前，我們公佈了 evinacumab 在純合子 FH 患者中 II 期概念驗證研究的積極數據。這些數據顯示，對於通常對他汀類藥物或 PCSK9 反應不佳的患者，在接受 2 次皮下注射依維那庫單抗後，其低密度脂蛋白膽固醇平均降低了 50%，且安全性良好。

Our immuno-oncology portfolio continues to progress. Our potentially pivotal study of Regeneron 2810, our PD-1 antibody, continues to enroll patients in the cutaneous squamous cell carcinoma study. We look forward to presenting data from our expansion in arm in cutaneous squamous cell carcinoma patients from our Phase I trial at an oral abstract session at the American Society of Clinical Oncology, or ASCO, in June. We also expect to initiate clinical studies in non-small cell lung cancer and basal cell carcinoma in 2017. Our second checkpoint inhibitor, Regeneron 3767, an antibody LAG3, is also currently in clinical development, where we are studying it both in the monotherapy setting and in combination with our PD-1 antibody. As a reminder, we expect additional I-O targets to enter development over the next several years. Additionally, our bispecific CD20xCD3 antibody is also currently being studied in the clinic, as both a monotherapy and in combination with our PD-1 antibody. Determining the optimal dosage levels of these therapies that are activating the immune system is very important, as witnessed by some of the toxicities demonstrated in other drug classes such as the CAR-Ts. While the process been slow, we believe we are nearing dose selection. Also in late-stage development is suptavumab, also known as Regeneron 2222, which is an antibody in development for respiratory syncytial virus, or RSV. Our Phase III study has finished enrolling patients, and we expect to report top line data from this study in the second half of the year. We are also advancing our Phase III program for fasinumab, our Nerve Growth Factor antibody for pain.

我們的免疫腫瘤學產品組合持續取得進展。我們正在繼續招募皮膚鱗狀細胞癌患者，進行 Regeneron 2810（一種 PD-1 抗體）的潛在關鍵性研究。我們期待在 6 月舉行的美國臨床腫瘤學會 (ASCO) 的口頭摘要會議上，展示我們 I 期試驗中皮膚鱗狀細胞癌患者擴展治療組的數據。我們也計劃於 2017 年啟動非小細胞肺癌和基底細胞癌的臨床研究。我們的第二個檢查點抑制劑 Regeneron 3767（一種 LAG3 抗體）目前也處於臨床開發階段，我們正在研究它在單藥治療和與我們的 PD-1 抗體聯合治療中的應用。再次提醒大家，我們預計未來幾年將有更多 I-O 標靶進入開發階段。此外，我們的雙特異性 CD20xCD3 抗體目前也在臨床上進行研究，既有單藥治療，也有與 PD-1 抗體合併治療。確定激活免疫系統的這些療法的最佳劑量水平非常重要，正如 CAR-T 療法等其他藥物類別所表現出的一些毒性所證明的那樣。雖然過程比較緩慢，但我們相信我們已經接近劑量選擇階段。處於後期研發階段的還有 suptavumab，也稱為 Regeneron 2222，它是一種正在研發用於治療呼吸道合胞病毒（RSV）的抗體。我們的 III 期研究已完成患者招募，預計今年下半年公佈研究的主要數據。我們也正在推進針對神經生長因子抗體 fasinumab（用於治療疼痛）的 III 期臨床試驗計畫。

Development in other parts of our early-stage pipeline continues to advance. Regeneron 2477, our Activin A antibody, is in clinical development for the treatment of the rare disease, fibrodysplasia ossificans progressiva, or FOP. We expect to begin a Phase II trial on this indication in the second half of 2017. We are also studying Regeneron 2477 in combination with trevogrumab, our antibody GDF8, in a Phase I trial, which is fully enrolled.

我們早期研發管線其他部分的開發工作也持續進行。Regeneron 2477 是我們的 Activin A 抗體，目前正處於臨床開發階段，用於治療罕見疾病進行性骨化性纖維發育不良症 (FOP)。我們預計將於 2017 年下半年開始針對此適應症的 II 期試驗。我們目前也正在 I 期試驗中研究 Regeneron 2477 與我們的抗體 GDF8 trevogrumab 聯合用藥，該試驗已完成全部受試者招募。

Finally, we also initiated a Phase I multiple ascending dose trial in asthma with Regeneron 3500, our antibody of interleukin-33 for inflammatory diseases in the first quarter of 2017. I think it's important to remind you that all of these programs and all the antibodies in our pipeline are entirely developed and discovered in-house.

最後，我們在 2017 年第一季啟動了 Regeneron 3500（一種用於治療發炎性疾病的白血球介素-33 抗體）在氣喘治療的 I 期多劑量遞增試驗。我認為有必要提醒大家，我們研發管線中的所有項目和所有抗體都是完全由我們內部開發和發現的。

Before I turn the call over to Bob, I want to take a moment to share my excitement about the first group of Regeneron Science Talent Search winners who were announced in March. Our sponsorship of this story high school science competition underscores our commitment to fostering the next generation of scientific leaders. After meeting these promising high school students, we feel -- are encouraged that our future is in good hands. With that, let me turn the call over to Bob Terifay.

在將電話交給鮑勃之前，我想花點時間分享我對3月份公佈的第一批Regeneron科學人才搜尋獎獲獎者的激動之情。我們贊助這項高中科學競賽，彰顯了我們致力於培養下一代科學領軍人才的承諾。在與這些前途無量的高中生見面後，我們感到——並且深受鼓舞，相信我們的未來掌握在可靠的人手中。那麼，現在讓我把電話交給鮑伯·特里費。

Thank you, George, and good morning, everyone. First quarter 2017 U.S. net sales of EYLEA, or aflibercept, were $854 million versus $781 million in the first quarter of 2016. This represents growth of 9% year-over-year. Ex U.S. net sales of EYLEA were $484 million compared to $419 million in the first quarter of 2016. This represents growth of 16% year-over-year. EYLEA is approved in approximately 100 countries for the treatment of wet AMD and DME. EYLEA continues to be the market-leading product among FDA-approved anti-VEGF agents for all of its approved indications in the United States. U.S. EYLEA net sales in the first quarter were impacted by a slight decrease in distributor or inventory as well as an increase in the gross to net margin, which Bob Landry will discuss in more detail. Based on qualitative market research survey we conducted in the first quarter, EYLEA market share remained consistent at approximately 66% of the FDA-approved anti-VEGF market. Also based on this survey, FDA-approved anti-VEGF therapies account for approximately 56% of the overall anti-VEGF market.

謝謝你，喬治，大家早安。2017 年第一季度，EYLEA（阿柏西普）在美國的淨銷售額為 8.54 億美元，而 2016 年第一季為 7.81 億美元。這相當於年增9%。安樂（EYLEA）在美國以外的淨銷售額為 4.84 億美元，而 2016 年第一季為 4.19 億美元。這相當於年增16%。EYLEA 已在約 100 個國家獲準用於治療濕性 AMD 和 DME。在美國，對於所有核准的適應症，EYLEA 仍然是 FDA 批准的抗 VEGF 藥物中的市場領先產品。美國EYLEA第一季的淨銷售額受到分銷商或庫存略微下降以及毛利率與淨利率之比上升的影響，Bob Landry將對此進行更詳細的討論。根據我們在第一季進行的定性市場調查，EYLEA 的市佔率保持穩定，在 FDA 核准的抗 VEGF 市場中約為 66%。根據這項調查，FDA 批准的抗 VEGF 療法約佔整個抗 VEGF 市場的 56%。

In terms of treatment regimens, as George noted, the variable-interval dosing regimens that are often used in the treatment of retinal diseases with the anti-VEGF agents can contribute to inadequate vision improvements, and we believe are not optimal for long-term maintenance of visual acuity. We are focused on educating retinal physicians and their patients on the benefits of using dosing regimens supported by evidence-based medicine and approved by the FDA.

就治療方案而言，正如喬治所指出的，使用抗 VEGF 藥物治療視網膜疾病時經常採用的可變間隔給藥方案可能會導致視力改善不足，我們認為這種方案對於長期維持視力而言並非最佳選擇。我們致力於教育視網膜醫師及其患者，讓他們了解使用實證醫學支持並經 FDA 批准的給藥方案的好處。

The recent approval and launch of Dupixent, or dupilumab, in the United States is the beginning of a new chapter for Regeneron. Dupixent was approved for the treatment of adults with moderate-to-severe atopic dermatitis at the end of March. As Len mentioned, the drug is commercially available to patients. Our field force is engaged with and educating the 7,000 or so targeted dermatologists, allergist and immunologists in the United States. The targeted patient population consist of roughly 300,000 patients with moderate-to-severe atopic dermatitis who have the greatest need. These are the patients who've exhausted all approved therapies and have failed or unable to tolerate unapproved use of immunosuppressants. Though it's quite early in the launch, we're pleased with what we have seen so far, and I'd like to share with you some of the details of the ongoing launch.

Dupixent（或 dupilumab）最近在美國獲得批准並上市，這標誌著 Regeneron 公司開啟了新的篇章。Dupixent 於 3 月底獲準用於治療中度至重度異位性皮膚炎成人患者。正如 Len 所提到的，這種藥物已面向患者上市。我們的現場團隊正在與美國約 7000 名目標皮膚科醫生、過敏科醫生和免疫學家進行溝通和培訓。目標患者群體由大約 30 萬名患有中度至重度異位性皮膚炎的患者組成，他們的需求最大。這些患者已經用盡了所有核准的療法，並且無法耐受或無效使用未經批准的免疫抑制劑。雖然發布還處於早期階段，但我們對目前為止所看到的感到滿意，我想和大家分享一下正在進行的發布的一些細節。

Firstly, we believe that the importance of good market access cannot be underestimated. To that end, we were very thoughtful about pricing Dupixent following multiple discussions with key stakeholders. Our goal for access is that utilization management criteria reflect good medical practice, which means that Dupixent should be prescribed by specialists such as dermatologist, allergist, and immunologists, to patients with moderate-to-severe atopic dermatitis who have not responded to maximal topical corticosteroids. We do not believe that requiring patients to take potentially toxic, off-label systemic immunosuppressants is appropriate now that Dupixent is approved and available. Two of the largest pharmacy benefits managers, or PBMs, have provided coverage right from the beginning. Coverage at these 2 PBMs account for approximately 25% of lives in commercial plans in the United States.

首先，我們認為良好的市場准入的重要性不容小覷。為此，我們在與主要利害關係人進行多次討論後，對Dupixent的定價進行了非常慎重的考慮。我們的目標是讓用藥管理標準反映良好的醫療實踐，這意味著對於中度至重度異位性皮膚炎患者，如果最大劑量的局部皮質類固醇治療無效，則應由皮膚科醫生、過敏科醫生和免疫學家等專科醫生開具 Dupixent 處方。我們認為，既然 Dupixent 已經核准上市，就不應該再要求患者服用可能具有毒性的、未獲批准的全身性免疫抑制劑。兩家最大的藥品福利管理公司（PBM）從一開始就提供了保險。這兩家藥品福利管理機構 (PBM) 的承保範圍約占美國商業保險計劃投保人數的 25%。

We've been actually -- actively engaged with additional payers. And based on these conversations, we believe are well positioned to receive broad coverage by the end of the year. We hope that these decisions will come early, since eligible patients have been waiting for a long time for a new treatment for this debilitating disease. To date, we estimate that over 1,800 physicians across all 50 states have already written a Dupixent prescription. There have been over 3,500 prescriptions for new patients written for Dupixent as of today. I would like to remind you that this number only represents the prescriptions written by physicians. It is not a reflection of the number of prescriptions that have been dispensed. Writing of prescriptions starts the coverage approval process. We estimate that the coverage decision should take several weeks, so it's too early for us to predict how many of these prescriptions will ultimately be approved for insurance coverage and dispensed. However, the early signs are encouraging, and we look forward to updating you during the second quarter.

我們一直在積極與其他付款方接洽。基於這些對話，我們相信我們有能力在年底前獲得廣泛的報導。我們希望這些決定能盡快出台，因為符合條件的患者已經等待這種致殘性疾病的新療法很久了。據我們估計，迄今為止，全美 50 個州已有超過 1800 名醫生開立了 Dupixent 處方。截至今日，已有超過 3500 名新患者開立了 Dupixent 處方。我想提醒您，這個數字僅代表醫生開出的處方數量。這並不反映處方藥的配發數量。開立處方是啟動醫保審核流程的第一步。我們估計健保覆蓋決定需要幾週時間才能做出，因此現在預測最終有多少處方藥會獲得醫保覆蓋並被配發還為時過早。不過，目前的跡象令人鼓舞，我們期待在第二季向您報告最新進展。

Outside of the United States, to remind everyone, in the fourth quarter of 2016, we filed a marketing authorization application, or MAA, for Dupixent and hope to have European approval by year-end.

提醒大家，在美國以外，我們在 2016 年第四季提交了 Dupixent 的上市許可申請 (MAA)，並希望在年底前獲得歐洲的批准。

Turning out to Kevzara, or sarilumab, our IL-6 receptor antibody for the treatment of rheumatoid arthritis. We've been granted an FDA action date of May 22. We'll be copromoting Kevzara in the United States. Our sales force is on board and is preparing for the anticipated launch. In Europe, Kevzara has received a positive opinion from the CHMP. And our collaborator, Sanofi-Genzyme, is gearing up for a potential launch in Europe later this year as well.

原來是 Kevzara，或稱為 sarilumab，是我們用來治療類風濕性關節炎的 IL-6 受體抗體。我們已獲得美國食品藥物管理局 (FDA) 的批准日期，即 5 月 22 日。我們將與 Kevzara 在美國進行聯合推廣。我們的銷售團隊已經做好準備，迎接即將到來的產品發布。在歐洲，Kevzara 已獲得 CHMP 的正面評價。我們的合作夥伴賽諾菲健贊也正在為今年稍後在歐洲的潛在上市做準備。

Turning now to PRALUENT, or alirocumab. As reported by Sanofi, net sales in the first quarter were $36 million worldwide, with the U.S. accounting for $25 million of the total. I would like to note that there was an impact in the marketplace from the injunction ruling against this in the first quarter of 2017, which was eventually stayed pending appeal. We are pleased to announce that PRALUENT was recently approved in a 300-milligram, once-monthly dosing regimen. We continue to be disappointed by the uptake of the PCSK9 inhibitor class, but remain optimistic, given the recent positive OUTCOMES data for this class. And our own OUTCOMES data are expected in early 2018, which, if positive, could have an impact on demand. We remain committed to our efforts to improve PRALUENT access and bring this important product to more patients who can benefit.

接下來我們來看看 PRALUENT，也就是 alirocumab。根據賽諾菲公司報告，第一季全球淨銷售額為 3,600 萬美元，其中美國市場貢獻了 2,500 萬美元。我想指出，2017 年第一季針對此項目的禁令裁決對市場產生了影響，該裁決最終因上訴而被中止執行。我們很高興地宣布，PRALUENT 最近獲準採用 300 毫克、每月一次的給藥方案。我們對 PCSK9 抑制劑類藥物的接受度仍然感到失望，但鑑於該類藥物最近在 OUTCOMES 研究中取得的積極數據，我們仍然保持樂觀。我們自己的 OUTCOMES 數據預計將於 2018 年初公佈，如果結果為正面，可能會對需求產生影響。我們將繼續致力於改善 PRALUENT 的可近性，並將這項重要產品帶給更多能夠受益的患者。

With that, let me turn the call over to our Chief Financial Officer, Bob Landry.

接下來，我將把電話交給我們的財務長鮑伯·蘭德里。

Thanks, Bob, and good morning, everyone. During today's call, I'll discuss our first quarter 2017 financial performance and highlight changes to a few of our full year 2017 guidance line items. In the first quarter of 2017, we earned $2.92 per diluted share from non-GAAP net income of $337 million. This represents a year-over-year increase in non-GAAP diluted EPS in net income of 22% and 23% respectively. I'd like to remind everyone that these growth numbers are based upon revised first quarter 2016 non-GAAP net income and EPS results, relating to the company's adoption of Accounting Standard Update 2016-09 in the second quarter of 2016. This accounting standard requires companies to recognize excess tax benefits in connection with employee exercises of stock options in the income statement. You can access these revised numbers and further information in our Form 10-Q, filed earlier this morning.

謝謝你，鮑勃，大家早安。在今天的電話會議上，我將討論我們 2017 年第一季的財務業績，並重點介紹我們對 2017 年全年業績指引的一些變化。2017 年第一季度，我們實現非 GAAP 淨利 3.37 億美元，每股攤薄收益為 2.92 美元。這意味著非GAAP稀釋後每股盈餘和淨利分別較去年同期成長了22%和23%。我想提醒大家，這些成長數據是基於 2016 年第一季修訂後的非 GAAP 淨收入和每股盈餘結果，這與公司在 2016 年第二季採用會計準則更新 2016-09 有關。此會計準則要求公司在損益表中確認員工行使股票選擇權所產生的超額稅優惠。您可以在我們今天早上早些時候提交的 10-Q 表格中查看這些修訂後的數據和更多資訊。

Regeneron's first quarter 2016 and 2017 non-GAAP net income excludes noncash, share-based compensation expense and includes the income tax effect of non-GAAP reconciling items. A full reconciliation of GAAP to non-GAAP earnings are set forth in our earnings release.

Regeneron 2016 年和 2017 年第一季的非 GAAP 淨收入不包括非現金的股份支付費用，但包括非 GAAP 調整項目的所得稅影響。我們的獲利報告中列出了 GAAP 收益與非 GAAP 收益的完整調整表。

Total revenues in the first quarter 2017 were $1.3 billion, which represented year-over-year growth of 10% over the first quarter of 2016. Net product sales were $858 million in the first quarter of 2017 compared to $784 million in the first quarter of 2016. EYLEA net product sales in the United States were $854 million in the first quarter of 2017 compared to $781 million in the first quarter of 2016, which represents an increase of 9%. For the full year 2017, we reaffirm our U.S. EYLEA net sales guidance of year-over-year single-digit percentage growth.

2017 年第一季總營收為 13 億美元，比 2016 年第一季年增 10%。2017 年第一季淨產品銷售額為 8.58 億美元，而 2016 年第一季為 7.84 億美元。2017 年第一季度，EYLEA 在美國的淨產品銷售額為 8.54 億美元，而 2016 年第一季為 7.81 億美元，成長了 9%。對於 2017 年全年，我們重申對美國安禮 (EYLEA) 淨銷售額年增個位數百分比的預期。

During the first quarter of 2017, EYLEA experienced a slight drawdown in U.S. distributor inventory levels yet remained within our normal 1- to 2-week targeted range. Additionally, we experienced an increase in EYLEA gross to net percentage as a result of 2 factors. First, earlier this year, we started offering a discount to all offices regardless of volume for competitive reasons; and second, there has been a small increase in the number of Medicaid patients being treated with EYLEA.

2017 年第一季度，EYLEA 在美國經銷商的庫存水準略有下降，但仍在我們正常的 1 至 2 週目標範圍內。此外，由於以下兩個因素，EYLEA 的毛利率（毛利率）有所上升。首先，今年早些時候，出於競爭原因，我們開始向所有辦公室提供折扣，無論業務量如何；其次，接受 EYLEA 治療的 Medicaid 患者人數略有增加。

Ex U.S. EYLEA net product sales, which are recorded by our collaborator, Bayer, were $484 million in the first quarter of 2017 as compared to $419 million in the first quarter of 2016, representing a 16% increase on a reported basis. On an operational basis or constant currency basis, sales increased approximately 19%. In the first quarter of 2017, Regeneron recognized $175 million from our share of net profits from EYLEA sales outside the United States. Total Bayer collaboration revenue for the first quarter of 2017 was $194 million. Total Sanofi collaboration revenue was $210 million for the first quarter of 2017. The Sanofi collaboration revenue line item primarily consists of reimbursement of Regeneron-incurred R&D expenses, reimbursement of Regeneron-incurred commercialization-related expenses and our share of profits or losses in connection with the commercialization of antibodies. In the first quarter of 2017, our share of losses in connection with the commercialization of PRALUENT, Dupixent and Kevzara, was $108 million. This can be found in table 4 of our earnings release. This loss represents increased spending related to the Dupixent and Kevzara launches, while we continue to proactively monitor and manage our investment in the global commercialization of PRALUENT. Netted within these losses were the global sales of PRALUENT, as recognized by our partner, Sanofi, which for the first quarter of 2017, were $36 million. The U.S. net sales of PRALUENT in the first quarter 2017 were clearly impacted from the news regarding the January 5, 2017, issuance of the permanent injunction, prohibiting the commercialization of PRALUENT in the United States, which was subsequently stayed pending appeal.

除美國以外，EYLEA 淨產品銷售額（由我們的合作夥伴拜耳公司記錄）在 2017 年第一季為 4.84 億美元，而 2016 年第一季度為 4.19 億美元，按報告數據計算增長了 16%。以營運成本或固定匯率計算，銷售額成長約 19%。2017 年第一季度，Regeneron 從 EYLEA 在美國以外地區的銷售淨利潤中確認了 1.75 億美元。2017 年第一季拜耳合作總營收為 1.94 億美元。2017 年第一季度，賽諾菲合作計畫的總收入為 2.1 億美元。賽諾菲合作收入項目主要包括：報銷 Regeneron 發生的研發費用、報銷 Regeneron 發生的商業化相關費用以及我們應得的抗體商業化利潤或虧損份額。2017 年第一季度，我們在 PRALUENT、Dupixent 和 Kevzara 的商業化過程中所承擔的損失為 1.08 億美元。這可以在我們發布的收益報告表 4 中找到。這一損失代表了與 Dupixent 和 Kevzara 上市相關的支出增加，同時我們將繼續積極監控和管理我們在 PRALUENT 全球商業化方面的投資。在這些損失中，包括了我們的合作夥伴賽諾菲確認的 PRALUENT 全球銷售額，2017 年第一季的銷售額為 3,600 萬美元。2017 年第一季 PRALUENT 在美國的淨銷售額明顯受到 2017 年 1 月 5 日發布的永久禁令的影響，該禁令禁止 PRALUENT 在美國進行商業化，隨後該禁令被暫停執行，等待上訴結果。

In the first quarter 2017, Other revenue increased significantly as compared to the first quarter of 2016. This increase was primarily due to reimbursements of research and development costs in connection with our collaboration agreement with Teva, which was entered into in September 2016. You can find a summary of the components of Other revenue in the MD&A section of our 10-K -- 10-Q.

2017 年第一季度，其他營收與 2016 年第一季相比大幅成長。這一增長主要是由於我們與梯瓦製藥於 2016 年 9 月簽訂的合作協議中涉及的研發費用的報銷。您可以在我們的 10-K 至 10-Q 表格的 MD&A 部分找到其他收入組成部分的摘要。

Turning now to expenses. Non-GAAP R&D expenses were $434 million for the first quarter of 2017. Our non-GAAP unreimbursed R&D expense, which is calculated as the total non-GAAP R&D expense less R&D reimbursement from our collaborators, was $189 million in the first quarter of 2017. Our press release includes all the information that is required to calculate unreimbursed non-GAAP R&D expense.

接下來談談費用。2017 年第一季非 GAAP 研發費用為 4.34 億美元。2017 年第一季度，我們的非 GAAP 未報銷研發費用（計算方法為非 GAAP 研發總費用減去合作方的研發報銷）為 1.89 億美元。我們的新聞稿包含了計算未報銷的非GAAP研發費用所需的所有資訊。

For 2017, we'd like to reiterate our previously provided guidance to non-GAAP unreimbursed R&D to be in the range of $950 million to $1.025 billion. Non-GAAP SG&A expense was $243 million for the first quarter of 2017. We are tightening and lowering our full year 2017 guidance for non-GAAP SG&A to $1.14 billion to $1.2 billion from our previous guidance range of $1.175 billion to $1.25 billion. Sanofi reimbursement of Regeneron commercialization-related expenses, a line item found within Sanofi collaboration revenue, was $74 million for the first quarter of 2017. We are lowering and tightening our full year 2017 guidance of Sanofi reimbursement of Regeneron commercialization-related expenses to be in the range of $385 million to $425 million from $400 million to $450 million.

對於 2017 年，我們重申先前提供的非 GAAP 未報銷研發支出預期，介於 9.5 億至 10.25 億美元之間。2017 年第一季非 GAAP 銷售、一般及行政費用為 2.43 億美元。我們將 2017 年全年非 GAAP 銷售、一般及行政費用預期從先前的 11.75 億美元至 12.5 億美元下調至 11.4 億美元至 12 億美元。2017 年第一季度，賽諾菲向 Regeneron 支付的商業化相關費用（該費用包含在賽諾菲合作收入中）為 7,400 萬美元。我們將 2017 年全年賽諾菲 Regeneron 商業化相關費用的報銷預期從 4 億美元至 4.5 億美元下調並收緊至 3.85 億美元至 4.25 億美元。

Before shifting to taxes, I would also like to note that operating costs related to our Limerick manufacturing facility that have not been capitalized were recognized in cost of goods sold, and therefore, had a negative impact on our first quarter 2017 gross margin as compared to the third and fourth quarters of 2016.

在討論稅收之前，我還想指出，與我們利默里克製造工廠相關的未資本化的營運成本已計入銷售成本，因此，與 2016 年第三季和第四季相比，對我們 2017 年第一季度的毛利率產生了負面影響。

Turning now to taxes. Our effective tax rate for the first quarter 2017 was approximately 42% as compared to approximately 45% for the first quarter 2016, which as stated earlier, has been revised for the impact of the adoption of ASU 2016-09. For the full year 2017, we continue to guide our effective tax rate to be in the range of 32% to 38%. This guidance includes an estimate of the full year tax benefit associated with stock-based compensation. As stated on previous calls, there will be volatility in our effective tax rate quarter-to-quarter, since the tax benefits of stock-based compensation can only be included based on actual exercises in the quarter. We expect the majority of our stock-based compensation tax benefits to be recognized in the latter part of the year, as we have a large number of stock options that vest or expire in the fourth quarter.

接下來談談稅務問題。2017 年第一季我們的實際稅率約為 42%，而 2016 年第一季的實際稅率約為 45%，如前所述，這已因採用 ASU 2016-09 的影響而進行了修訂。2017 年全年，我們將繼續把實際稅率控制在 32% 至 38% 的範圍內。該指南包括與股票選擇權激勵相關的全年稅收優惠的估算。如同先前電話會議所述，我們的實際稅率會逐季度波動，因為股票選擇權激勵的稅收優惠只能根據當季實際行權情況計算。我們預計大部分股票選擇權激勵稅收優惠將在今年下半年確認，因為我們有大量股票選擇權將在第四季度歸屬或到期。

From a cash flow and balance sheet perspective, we ended the first quarter of 2017 with cash and marketable securities of $2.3 billion. Our capital expenditures for the first quarter of 2017 were $50 million. We are tightening and lowering our full year 2017 capital expenditures guidance to be in the range of $300 million to $350 million from our previous guidance range of $375 million to $425 million. We note that this represents a significantly lower capital spend in the previous 2 years, as we are nearing completion of a few major capital projects, including our drug substance manufacturing facility in Limerick, Ireland. Also, we finalized the refinancing related to our Tarrytown headquarters in March 2017. Further details can be found on our website in the 8-K, filed in association with this transaction, or in our most recent 10-Q that was filed earlier this morning.

從現金流量和資產負債表的角度來看，截至 2017 年第一季末，我們擁有現金和有價證券 23 億美元。2017 年第一季度，我們的資本支出為 5,000 萬美元。我們將 2017 年全年資本支出預期從先前的 3.75 億美元至 4.25 億美元下調至 3 億至 3.5 億美元。我們注意到，這代表著過去兩年資本支出大幅減少，因為我們即將完成幾個重大資本項目，包括我們在愛爾蘭利默里克的藥物原料生產設施。此外，我們於 2017 年 3 月完成了與塔里敦總部相關的再融資。更多詳情請參閱我們網站上與本次交易相關的 8-K 文件，或我們今天早上早些時候提交的最新 10-Q 文件。

With that, I'd like to turn the call back to Manisha.

那麼，我想把電話轉回給瑪妮莎。

Thank you, Bob. Sylvia, we'd now like to open the line for Q&A. In the interest of time, we'd like to request that you limit yourself to 1 question. We will be available in the office after the call for a follow-up Q&A.

謝謝你，鮑伯。西爾維亞，我們現在開始進行問答環節。為了節省時間，請您只提一個問題。通話結束後，我們將在辦公室進行後續問答。

(Operator Instructions) And our first question comes from Geoff Porges from Leerink Partners.

（操作說明）我們的第一個問題來自 Leerink Partners 的 Geoff Porges。

Len, don't take this the wrong way, but congratulations on the cash flow and on filing the Q, the account. I wanted to ask you, George, just a few questions, related questions on the pipeline. Looking through the Q this morning, there's no mention of your C5 antibody nor of your CD3 bispecific. Could you just comment on the status of those programs? And then on the ODYSSEY OUTCOMES study, given the timing that you provided to us, can you give us a sense of what you estimate the median duration of exposure will be in the study? And what effect that might have on the likely effect size given the offset of the lower dosing that you may have with some patients?

Len，別誤會我的意思，但還是要祝賀你現金流狀況良好，並且提交了季度報告（財務報表）。喬治，我想問你幾個問題，一些與管道相關的問題。今天早上查看詢問記錄時，沒有提到您的 C5 抗體或 CD3 雙特異性抗體。能否介紹一下這些專案的進度？那麼，關於 ODYSSEY OUTCOMES 研究，鑑於您向我們提供的時間信息，您能否大致估算一下該研究中暴露的中位數持續時間是多少？考慮到某些患者可能採用較低劑量，這會對預期療效產生什麼影響？

Yes. A lot of questions in there. First, we did actually comment on the CD20xCD3 bispecific, that it's moving along. That basically, we've spent a lot of time, because as obviously you've all noticed that there have been concerns with similar types of agents as well as the CAR-T approaches in terms of really getting the right dose and avoiding very dangerous toxicity. So we've been very careful about dosage selection in that program, and we're hoping very close to be to the point where we can initiate larger trials.

是的。裡面有很多問題。首先，我們確實評論了 CD20xCD3 雙特異性抗體，它正在取得進展。基本上，我們花了很多時間，因為正如你們都注意到的，對於類似類型的藥物以及 CAR-T 方法，人們一直存在著關於如何獲得正確劑量和避免非常危險的毒性的擔憂。因此，我們在該計畫中對劑量選擇非常謹慎，我們希望很快就能啟動更大規模的試驗。

In terms of our C5 antibody, I don't know how much we've said publicly about it, but I guess we said that we will be in the clinic with this year. And I'm sorry I didn't make any reference to it, that was just an oversight on my part. In terms of our OUTCOMES study, I have to say that there are so many differences between our design and the 4-year design that I think it's almost impossible to try to model it and figure out are the results going to be substantially different. I think that the 4-year data pretty strongly shows that its results are very consistent with the sort of benefits that one obtains in terms of cardiovascular outcomes with the proportional LDL lowering. And that's pretty much exactly what we hope to show, that we are pretty much on the same sort of curve as the statin, and now the first results that are coming out of the PCSK9 class.

關於我們的 C5 抗體，我不知道我們公開談論過多少，但我想我們說過今年我們會進行臨床試驗。很抱歉我沒有提及此事，這只是我的疏忽。就我們的 OUTCOMES 研究而言，我必須說，我們的設計與 4 年設計之間存在如此多的差異，以至於我認為幾乎不可能對其進行建模並弄清楚結果是否會有實質性的不同。我認為，4 年的數據有力地表明，其結果與按比例降低 LDL 所帶來的心血管結果益處非常一致。而這正是我們希望展示的，我們與他汀類藥物的曲線基本上相同，現在 PCSK9 類藥物的第一批結果也出來了。

Operator, next question, please.

接線員，請問下一個問題？

Our following question comes from Chris Raymond from Raymond James.

接下來的問題來自 Raymond James 公司的 Chris Raymond。

Question on Dupixent. So according to some of our market checks, that -- looks like that the breakdown among patients by age is at roughly half are adults, you've got maybe 20% adolescents. But then there's another maybe sort of 33% or 34% that are treated by docs today that are under 12. I know you guys have talked about the clinical path for kids 6 to 12. But, at least according to our data anyway, derms today have a sizable patient load under 6, and there's probably many more who haven't made their way to a derm. So can you maybe talk about the potential to get at that market of kids under 6? Like for example, some of our data says that maybe as much as 12% or so patient load are actually even under 2. So what's the setup, I guess, for treating kids younger?

關於Dupixent的問題。根據我們的一些市場調查，看起來患者按年齡劃分，大約一半是成年人，青少年可能佔 20%。但還有大約 33% 或 34% 的患者，他們現在接受醫生的治療時年齡在 12 歲以下。我知道你們討論過 6 至 12 歲兒童的臨床路徑。但至少根據我們的數據來看，如今皮膚科醫師平均要照顧 6 名以下的患者，可能還有更多患者沒有去看皮膚科。那麼，您能否談談如何開拓6歲以下兒童市場？例如，我們的一些數據顯示，可能有多達 12% 的患者年齡甚至不到 2 歲。那麼，對於治療較小的孩子，我們該如何安排呢？

Yes. You are absolutely right that a lot of these allergic diseases, it's not only atopic dermatitis but eosinophilic esophagitis and so forth and so on, unfortunately afflict the very young. There's a very deliberate process that we work with, with regulatory authorities to progress to the youngest in our population, because we all feel that we have to be very careful. And we're working very closely with the FDA to follow along those guidelines to be able to bring this treatment down the line to the youngest of patients who really need it. But as you said, there is a very important unmet need in these populations for all sorts of allergic diseases.

是的。您說得完全正確，很多過敏性疾病，不僅是異位性皮膚炎，還有嗜酸性食道炎等等，不幸的是，它們都會影響到非常年幼的孩子。我們與監管機構合作，制定了一套非常周密的流程，逐步將這項技術推廣到我們人口中最年輕的群體，因為我們都覺得我們必須非常謹慎。我們正與 FDA 密切合作，遵循這些指導方針，以便將這種療法推廣到真正需要它的最年輕的患者身上。但正如你所說，這些人群在各種過敏性疾病方面存在著非常重要的未滿足需求。

One thing just to amplify what George said is that the FDA clearly recognizes this, they had an advisory group and they, in fact, pushed us to start the younger populations even sooner than one might normally in the development program. So I think, we get it, the agency gets it. They've granted us, I think, breakthrough status for -- I can't remember which age group, maybe that -- Manisha do you remember?

喬治所說的一點是，FDA 顯然也認識到了這一點，他們成立了一個諮詢小組，事實上，他們敦促我們比正常情況下更早開始對年輕群體進行研發。所以我覺得，我們明白了，機構也明白了。我認為他們授予了我們突破性地位——我不記得是哪個年齡組了，也許是那個年齡組——瑪妮莎，你還記得嗎？

12 to 17.

12至17。

12 to 17. So I mean, I think everybody gets it. We've got good early data. And as George said, we're sort of doing this logically and trying to move to where that need is. Of course the chronicity of treatment from a commercial point of view, once you make it to adulthood and you have the disease, we should be clear that this is -- we don't view this as treating an episodic disease. These people have disease chronically and will need chronic treatment, which may be different than children who can possibly outgrow this.

12至17。所以我覺得大家都懂。我們獲得了不錯的早期數據。正如喬治所說，我們正在以合乎邏輯的方式做這件事，並努力滿足這種需求。當然，從商業角度來看，治療的慢性性，一旦你成年並患上這種疾病，我們應該明確一點——我們不認為這是在治療一種偶發性疾病。這些人患有慢性疾病，需要長期治療，這可能與兒童不同，因為兒童有可能隨著年齡增長而痊癒。

So should we see a trial then start maybe for kids under 6 at some point? I guess that's the key question.

那麼我們是否應該先進行試驗，然後再考慮在某個時候對6歲以下兒童進行試驗呢？我想這才是關鍵問題。

Yes. You will see us moving towards younger age groups steadily.

是的。你會看到我們穩定地向更年輕的年齡層拓展。

Next question, please.

下一個問題。

Our following question comes from Ying Huage from Bank of America Merrill Lynch.

接下來的問題來自美國銀行美林證券的英華格。

I have one question on EYLEA. It seems that you reported pretty strong numbers for EYLEA sales in the U.S. and relatively [probably] strong numbers for LUCENTIS. So does that mean the market is growing at a higher rate this year? Or are the branded medicines are taking share from off-label Avastin? And then maybe for George, a quick question on PD-1 trial for non-small cell lung cancer. Given all this debate around PD-L1 levels, I was wondering if you can comment how do you plan to design that trial in terms of stratification of PD-L expression levels. And do you see any differentiation from your PD-1 and the other marketed drugs?

我有一個關於愛立信的問題。看來你們報告的EYLEA在美國的銷售數據相當強勁，而LUCENTIS的銷售數據也相對強勁（可能）。那是否意味著今年的市場成長更快？或者說，品牌藥是否正在搶佔非適應症用阿瓦斯汀的市佔率？然後，也許可以問喬治一個關於 PD-1 治療非小細胞肺癌試驗的簡短問題。鑑於目前圍繞 PD-L1 水平的種種爭論，我想知道您能否就您計劃如何根據 PD-L 表達水平進行分層來設計該試驗發表一些看法。您認為您的PD-1與其他上市藥物有何不同？

Okay. So let's take that. Ying, thanks, in 2 parts. First, Bob can address what he thinks to market sizes overall for anti-VEGF therapy, and what the branded versus nonbranded split is, and then George can deal with your question on lung cancer and PD-1.

好的。那就這樣吧。瑩，謝謝，分成兩部分。首先，Bob 可以談談他對 VEGF 抗病毒療法整體市場規模的看法，以及品牌藥和非品牌藥的比例，然後 George 可以回答你關於肺癌和 PD-1 的問題。

I think it's -- as we mentioned, the overall branded anti-VEGF market year-over-year grew by 9%, which is consistent with what we saw in our growth. So you can assume that both products had approximately 9% growth. We did mention that in terms of what portion of the market is the branded market, it's approximately 65%. So...

我認為——正如我們所提到的，品牌抗 VEGF 市場整體年增了 9%，這與我們自身的成長一致。因此，您可以假設這兩種產品的成長率約為 9%。我們確實提到過，品牌市場佔市場份額的比例約為 65%。所以...

Which hasn't really changed. So the market itself seems to be growing, although our figures showed a slight inventory drawdown. We don't know well enough what happened with LUCENTIS and whether there was some destocking at the end of last quarter and then restocking with their new formulation or not. So to get more granularity on that, Ying, you'll have to pass it through Roche. George?

這一點其實並沒有改變。因此，儘管我們的數據顯示庫存略有下降，但市場本身似乎正在成長。我們不太清楚 LUCENTIS 發生了什麼，也不知道上個季度末是否進行過清倉，然後又用新配方重新進貨。所以，Ying，要獲得更詳細的信息，你需要透過羅氏公司進行諮詢。喬治？

Yes, about PD-1 and PD-L1 levels and so forth. I don't think there is actually that much of a controversy. I think that all the data shows that in most cases, higher PDL expression correlates with better responses. The controversy, I think that you're referring to has to do with the fact that the first-line lung study from Merck with KEYTRUDA was very impressively positive, whereas the very similar population studied with the BMS drug was not. And this did not really seem to be dependent on the PDL levels. People are really working hard to understand why the Bristol drug showed very disappointing results in that study. Our goal is to show that our drug is very effective in the various lung cancer indications. And we're designing, we hope and we believe, robust studies to demonstrate that. And we are, I believe, going to be announcing that we're going to be -- when we initiate these studies in the very, very near future.

是的，關於PD-1和PD-L1水平等等。我覺得這其實不算是什麼爭議。我認為所有數據都表明，在大多數情況下，PDL表達水平越高，治療效果越好。我認為你指的是這場爭議，因為默克公司使用 KEYTRUDA 進行的肺癌一線研究結果非常令人矚目，而百時美施貴寶公司使用類似藥物進行的研究結果卻並非如此。而且這似乎與PDL水平無關。人們正在努力了解為什麼布里斯託的藥物在那項研究中顯示出了非常令人失望的結果。我們的目標是證明我們的藥物對各種肺癌適應症都非常有效。我們正在設計、希望並相信能夠證明這一點的可靠研究。我相信，我們將在不久的將來宣布，我們將啟動這些研究。

Good. Next question.

好的。下一個問題。

Our following question comes from Ronny Gal from Bernstein.

接下來的問題來自伯恩斯坦公司的 Ronny Gal。

A question for Bob. Could you contrast for us a little bit the cost of launching PRALUENT versus Kevzara and Dupixent? Essentially, when you think about the magnitude of cost to launch those 2 drugs, how do they differ? And second, if you think about the international operations of PRALUENT, roughly when should we expect them to break even? Essentially, what revenue do you need internationally to breakeven on that product?

問鮑伯一個問題。您能否為我們比較一下 PRALUENT 與 Kevzara 和 Dupixent 的上市成本？從本質上講，當你考慮推出這兩種藥物的成本規模時，它們之間有什麼區別？其次，如果你考慮 PRALUENT 的國際業務，我們大概應該預期他們何時才能達到收支平衡？從本質上講，你需要多少國際收入才能讓該產品達到損益兩平？

I'll talk into generalities, I'm not going to talk specifics in the financials. But what I can say is there is a major difference between Dupixent and PRALUENT in terms of the targeted audiences. PRALUENT is competing in hypercholesterolemia market. That is a condition that's primarily treated by primary care physicians, but also is treated by a large group of cardiologists and lipidologists. So in terms of the effort on PRALUENT, one has to go broad to be able to get to the large physician audience. In terms of Dupixent, as we mentioned, in the United States, we're targeting about 7,000 specialists. So the effort is more limited in terms of who you have to call on, and what types of support you have to give to those patients. In terms of ex U.S., it's premature to talk about breakeven.

我會談些整體情況，不會談到財務上的具體細節。但我可以肯定的是，Dupixent 和 PRALUENT 在目標受眾方面存在重大差異。PRALUENT正在高膽固醇血症市場展開競爭。這種疾病主要由初級保健醫生治療，但也由大量心臟科醫生和血脂專家治療。因此，就 PRALUENT 的研發工作而言，必須採取廣泛的策略才能接觸到大量的醫生群體。關於 Dupixent，正如我們所提到的，在美國，我們的目標客戶是大約 7,000 名專家。因此，在需要求助的對像以及需要為這些患者提供哪些類型的支援方面，工作量會受到更多限制。就美國以外的市場而言，現在談論損益平衡還為時過早。

And just to reiterate what Bob said, I think if you do the math, we've hit about -- in the neighborhood of about 25% of the doctors we targeted have actually written a prescription, which is really pretty good at this stage of the launch.

正如鮑勃所說，我認為如果你計算一下，我們已經達到了——大約 25% 的目標醫生實際上已經開出了處方，這在產品推出的這個階段真的相當不錯。

Next question?

下一個問題？

Our following question comes from Carter Gould from UBS.

接下來的問題來自瑞銀集團的卡特古爾德。

I got one for George or Leon. Regeneron 2222, The PR mentioned enrollment was 1,200, but I think you've been targeting 1,500-plus patients. This impact your stat plan for the primary endpoint or change how we should be thinking about the likelihood of hitting on onetime season dosing? And, I guess, if anyone wanted to comment on the competitiveness of this program given Sanofi's history with your program and subsequent decision to partner with Medimmune, that would be appreciated as well.

我買了一個給喬治或里昂。Regeneron 2222，新聞稿中提到入組人數為 1200 人，但我認為你們的目標是 1500 名以上的患者。這會影響您針對主要終點的統計計劃，或改變我們對一次性季節性給藥成功可能性的看法？我想，如果有人想就該項目的競爭力發表評論，考慮到賽諾菲與你們項目的過往經歷以及隨後決定與 Medimmune 合作，那也將不勝感激。

I'll comment on the latter, and George can comment on the former. The decisions that people make aren't always the best ones. And we love our partnership with Sanofi. But remember they are the ones that turned back EYLEA. So we'll see them in the marketplace, and we think we have a very good entry and we love the friendly competition with a really good partner. Now George can get more into the specifics.

我會就後者發表評論，喬治可以就前者發表評論。人們所做的決定並不總是最佳決定。我們非常珍惜與賽諾菲的合作關係。但請記住，是他們讓EYLEA倒下了。所以我們會在市場上看到它們，我們認為我們有一個非常好的切入點，我們很喜歡與一個非常優秀的合作夥伴進行良性競爭。現在喬治可以更詳細地談談細節了。

Well, as you know, the power of the study is more dependent on events rather than numbers of patients that actually enrolled. We feel, though there's always concerns, we feel that we're adequately powered and we're hoping that the study will meet its expectations.

如您所知，這項研究的效力更取決於事件的發生情況，而不是實際入組的患者人數。雖然總是會有一些擔憂，但我們覺得我們有足夠的實力，並且希望這項研究能達到預期效果。

Operator, next question, please.

接線員，請問下一個問題？

Our following question comes from Terence Flynn from Goldman Sachs.

接下來的問題來自高盛的 Terence Flynn。

Maybe, George, I was intrigued by your comments on the long-term EYLEA VIEW data and the importance of adhering to the approved dosing interval. Do you think that proposition would also apply to Novartis' RTH? Recognizing we don't have the Phase III data yet, but as you think about what they're trying to accomplish with their drug, maybe help us think about the longer-term -- importance of longer-term data.

喬治，或許我對你關於 EYLEA VIEW 長期數據的評論以及堅持批准的給藥間隔的重要性很感興趣。你認為這個觀點也適用於諾華的RTH嗎？我們雖然知道目前還沒有 III 期數據，但是，當你思考他們想透過這種藥物實現的目標時，也許可以幫助我們思考更長遠的目標——長期數據的重要性。

Yes. I think it will be a very long time before one has the long-term data with a new agent to be able to say whether or not they could possibly not only cause initial visual gains but maintain them, which is, I think, is more important over the 4- or 5-year time intervals. Right now, we have the only such study that shows that and the only such data. I think that the field has been going in the wrong direction, focusing on convenience, okay? As opposed to focusing on vision. We all know, we all cherish our vision. There is nothing more important than maintaining our vision. And we think that there's been an over focus on convenience as opposed to on bringing back -- these drugs have the ability to give back vision. And we have now shown that there's at least 1 drug with 1 regimen or -- an assorted regimen that has the ability to maintain this over the long-term. And I think that we all have to focus on that and less on trying to save an injection or 2 per year, which is at most, what all of these nonmedicine-based approaches have been doing. I think this is really important for the field, and we hope, as Bob says, that doctors can be educated about this and stop experimenting on their patients and instead follow the FDA guidelines.

是的。我認為，要獲得關於一種新藥物的長期數據，從而能夠判斷它是否不僅能帶來最初的視力改善，還能維持這種改善，還需要很長時間。我認為，在 4 到 5 年的時間跨度內，維持視力改善更為重要。目前，我們擁有唯一一項能夠證明這一點的研究和唯一此類數據。我認為這個領域的發展方向錯了，過於注重便利性，好嗎？與專注於視覺不同。我們都知道，我們都很珍惜我們的視力。沒有什麼比保持我們的願景更重要。我們認為，人們過於注重便利性，而忽略了恢復視力——這些藥物有能力恢復視力。我們現在已經證明，至少有一種藥物，配合一種治療方案，或配合多種治療方案，能夠長期維持這種療效。我認為我們都應該把注意力放在這一點上，而不是試圖每年節省一兩次注射，因為所有這些非藥物療法最多也只能做到這一點。我認為這對該領域來說非常重要，我們希望，正如鮑勃所說，醫生們能夠了解這一點，停止在病人身上進行實驗，而是遵循 FDA 的指導方針。

Operator, next question, please.

接線員，請問下一個問題？

Our next question comes from Alethia Young from Credit Suisse.

下一個問題來自瑞士信貸的阿萊西亞·楊。

I just had one on EoE. Can you talk maybe about the potential market size and thoughts on endpoints? I know there's been some conversations in public domains around the FDA discussing end points.

我剛剛在EoE上遇到了一個。您能否談談潛在的市場規模以及對終端設備的看法？我知道在公共領域，FDA 內部已經有一些關於終點的討論。

So in terms of market size, this is very difficult to ascertain. We know that the market size "is increasing." What we don't know whether that's because there's more patients being diagnosed or it's just tracking the general increase in allergic diseases. So we remind you that there is a strong set of evidence to indicate that eosinophilic esophagitis can be a manifestation of food allergy. And so as an allergy, we're seeing lots of these increase. The actual numbers, we just don't feel we have a good handle on the number of patients. If Bob wants to give a shot at it, that would be great. In terms of end points, we saw clear results on -- as George mentioned, both on the patient-reported outcomes as well as the hard and atomic. In some cases in the past for example, an ulcer disease or erosive esophagitis, and FDA has used end points such as healing actually by endoscopy measured. We have not had a conversation yet with the Agency about these data. They're very new to us. So we will do that and then sort of let you know what it's going to take for -- from an approval perspective. Bob, you have a comment on this some more?

因此，就市場規模而言，這很難確定。我們知道市場規模「正在擴大」。但我們不知道這是因為確診患者人數增加，還是只是反映了過敏性疾病總體數量的增長。因此，我們提醒您，有大量證據表明嗜酸性食道炎可能是食物過敏的一種表現。因此，作為一種過敏症，我們看到這類病例正在增加。實際數字方面，我們感覺無法準確掌握患者人數。如果鮑伯願意嘗試一下，那就太好了。就終點而言，我們看到了明確的結果——正如喬治所提到的，無論是在患者報告的結果方面，還是在硬性和原子性方面。例如，在過去的一些案例中，潰瘍病或糜爛性食道炎，FDA 使用了諸如透過內視鏡測量的癒合等終點指標。我們尚未就這些數據與該機構進行溝通。它們對我們來說非常陌生。所以我們會這樣做，然後告訴你從審核的角度來看需要做些什麼。鮑勃，你對此還有什麼要補充的嗎？

Yes. Well, I think Len really nailed the situation with EoE. It is a disease that has generally been under diagnosed. The current estimate in the U.S., among adults, is somewhere between 100,000 and 200,000. But the true instance could be higher based on under diagnosis.

是的。我覺得 Len 對《新世紀福音戰士劇場版：Air/真心為你》的劇情把握得非常到位。這種疾病通常未被充分診斷​​。目前美國成年人中的估計人數在 10 萬到 20 萬之間。但根據漏診情況，實際病例數可能更高。

Next question, please.

下一個問題。

Our next question comes from Cory Kasimov from JPMorgan.

我們的下一個問題來自摩根大通的科里·卡西莫夫。

I wanted to ask on Dupi as well and kind of how you're thinking about the dynamics of a bolus of severe atopic dermatitis patients for Dupixent as we see these early trends and think about the launch going forward. A thousand scripts written per week is obviously quite an encouraging number, but one obviously we can't expect to go up forever. So how much pent-up demand do you see out there now that you are in the field?

我還想問一下關於Dupixent的問題，以及鑑於我們看到的這些早期趨勢，以及您如何看待大量重度異位性皮膚炎患者使用Dupixent的動態，並考慮未來的上市計劃。每週創作一千個劇本顯然是一個相當令人鼓舞的數字，但我們顯然不能指望這個數字永遠增長下去。那麼，既然您已經進入這個領域，您認為目前市場上有多少被壓抑的需求？

That's also a very difficult question to get a hard answer on. When you talk to some doctors, they'll tell you, well, they had a list of patients that they were going to bring in. When you talk to other doctors, they'll tell you that they're not -- the patients are just sort of showing up and they're incident patients, which they're constantly seeing in their practice and that patients are aware of their product and wanted to discuss it with their doctors. How long this goes on? Well, I don't know. And we don't have enough information to see what the trends are. Have we peaked because of a bolus? Are we increasing still? Are we decreasing? Really too early to tell you. We do know that we're focusing on in the 100,000 to 200,000 patient range who are the most difficult to treat. I think with any new drug class, some of it is also going to be dependent upon the doctors' reaction. The great data that I think we have in our label encourages doctors to try the product. But it will take individual experience and successes with individual patients for them to continue to use it. And so far, we even have heard some early anecdotes on that line as well. So bottom line is, we just don't have enough information to guide you. We'd like to know ourselves. And I think anybody's guess at this point is as good as anybody else.

這也是個很難得到確切答案的問題。當你和一些醫生交談時，他們會告訴你，他們有一份要接診的病人名單。當你和其他醫生交談時，他們會告訴你並非如此——病人只是突然出現，而且都是偶發病例，他們在診療過程中經常遇到這種情況，病人了解他們的產品，並想和醫生討論一下。這種情況會持續多久？嗯，我不知道。我們沒有足夠的資訊來判斷趨勢是什麼。我們是否因為注射了過量的藥物而達到了高峰？我們還在成長嗎？我們是在減少嗎？現在告訴你還為時過早。我們知道，我們重點關注的是患者人數在 10 萬到 20 萬之間的群體，他們是治療難度最大的群體。我認為任何一種新藥的療效，部分也取決於醫生的反應。我認為我們產品標籤上提供的可靠數據能夠鼓勵醫生嘗試使用該產品。但只有親身經歷並成功治療個別患者後，他們才會繼續使用這種方法。到目前為止，我們甚至還聽到了一些關於這條線路的早期軼事。所以歸根結底，我們沒有足夠的資訊來指導您。我們想了解自己。我認為在這一點上，任何人的猜測都一樣好。

I think Len makes an important point. There are patients in need of this important therapy. And our job beyond this initial bolus is really to educate physicians and patients on the fact that there is now something that could help these patients.

我認為倫的觀點很重要。有些病人需要這種重要的治療。除了最初的這劑強心劑之外，我們的工作實際上是教育醫生和患者，讓他們了解現在有某種方法可以幫助這些患者。

We do want to reach out and we'll reach out appropriately, because -- to patients directly, because we believe, as Bob was just suggesting, that there are patients who have dropped out of the medical system because they've been to so many different doctors with so many different regimens and nothing has helped them. That making them aware that there is something new is an important part of our effort.

我們確實想與患者溝通，而且我們會以適當的方式進行溝通，因為——直接與患者溝通，因為我們相信，正如鮑勃剛才所建議的那樣，有些患者已經脫離了醫療系統，因為他們看過太多不同的醫生，嘗試過太多不同的治療方案，但都沒有對他們有所幫助。讓他們意識到有新事物存在，是我們工作的重要部分。

Next question.

下一個問題。

Operator in the (inaudible), we have one last question. After that, we will be in our office to take additional follow-up question. And our apologies to those who are in queue and who didn't get a chance to ask their questions.

接線生（聽不清楚），我們還有一個問題。之後，我們會在辦公室解答其他後續問題。對於正在排隊但沒機會提問的人，我們深表歉意。

Our next question comes from Hartaj Singh from Oppenheimer.

下一個問題來自奧本海默公司的哈塔吉·辛格。

We just noticed, actually a slightly different take just on your operating expenditures. You've managed your P&L very well this quarter. It looks like on just a straight run rate into the end of the year, you would actually come below your guidance. And with just 110 million shares outstanding, that's not trivial. Just any thoughts on the progression of operating expenditures and how you're thinking of managing it with the Kevzara launch and all the other activities?

我們剛剛注意到，實際上，您對營運支出的看法略有不同。本季你的損益管理做得非常好。看起來，如果僅以目前的運行速度到年底，你的實際業績實際上會低於預期。而該公司僅有 1.1 億股流通股，這可不是小事。關於營運支出的發展情況，以及您打算如何配合 Kevzara 的上市和其他各項活動來管理營運支出，您有什麼想法嗎？

Yes. No, thanks for the question. You're right, in terms of the guidance that we've set for the full year and where we are for the first quarter. As you can imagine, we do, obviously, spend a lot of time and effort in terms of forecasting where we're going to come out in a bi-quarter basis. And the quarters are not always consistent. We are going to be in kind of full bloom in the second quarter, when we get, hopefully, our PDUFA approval with Kevzara, and we'll have our full strength out there in the marketplace. And again, we do expect higher expenditures with regards to SG&A and with unreimbursed R&D in the second half of 2017.

是的。不，謝謝你的提問。你說得對，就我們為全年設定的業績指引以及我們第一季的進展而言。正如你所想，我們顯然會花費大量時間和精力來預測我們每兩個季度的表現。而且季度數並不總是一致的。預計在第二季度，我們將迎來全面發展，屆時，我們希望能夠獲得 Kevzara 的 PDUFA 批准，並在市場上展現我們全部的實力。我們預計 2017 年下半年銷售、管理及行政費用以及未報銷的研發費用將會增加。

Thank you, operator. That concludes our call today.

謝謝接線生。今天的通話到此結束。

Thank you, ladies and gentlemen. This concludes today's conference. Thank you for participating. You may now disconnect.

謝謝各位女士、先生。今天的會議到此結束。感謝您的參與。您現在可以斷開連線了。