雷傑納榮製藥 (REGN) 2016 Q4 法說會逐字稿

Welcome to the Regeneron Pharmaceuticals Q4 2016 earnings conference call. My name is Nicole, and I'll be your operator for today's call.

歡迎參加再生元製藥公司2016年第四季財報電話會議。我是妮可，將擔任今天會議的接線生。

(Operator Instructions)

（操作說明）

Please note that this conference is being recorded. I will now turn the call over to Dr. Michael Aberman.

請注意，本次會議正在錄音。現在我將把電話交給邁克爾·阿伯曼博士。

Dr. Aberman, you may begin.

阿伯曼博士，你可以開始了。

Thank you.

謝謝。

Good morning, everybody. I hope you are all staying safe if you are on the East Coast. Welcome to Regeneron Pharmaceuticals fourth-quarter and full-year 2016 conference call. An archive of this webcast will be available on our website under Events and Presentations for 30 days.

各位早安。若您身處美國東岸，希望您一切平安。歡迎參加再生元製藥公司2016年第四季及全年業績電話會議。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; Dr. George Yancopoulos, Founder, Scientist, President and Chief Scientific Officer; Bob Terifay, Executive Vice President, Commercial; and Bob Landry, Chief Financial Officer.

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；創辦人、科學家、總裁兼首席科學官 George Yancopoulos 博士；商業執行副總裁 Bob Terifay；以及財務長 Bob Landry。

After our prepared remarks, we will open the call for Q&A. I would also like to remind you that remarks made on this call include forward-looking statements about Regeneron. Such statements may include, but are to limited to, those related to Regeneron and its products, product candidates and business, sales and expense forecast, financial forecast, development programs, collaborations, finances, regulatory matters, coverage and reimbursement matters, intellectual property, litigation matters, and competition.

在我們完成事先準備好的演講後，我們將開放問答環節。同時，我也想提醒各位，本次電話會議的發言包含有關Regeneron公司的前瞻性陳述。這些陳述可能包括但不限於與Regeneron公司及其產品、候選產品和業務、銷售和支出預測、財務預測、研發項目、合作、財務狀況、監管事宜、醫保覆蓋和報銷事宜、知識產權、訴訟事宜以及競爭相關的內容。

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 K for the year ended December 31, 2016, which will be filed with the SEC later today. Regeneron does not undertake any obligation to update publicly any forward-looking statement. Whether as a result of new information, future events, or otherwise.

每項前瞻性聲明均受風險和不確定性因素的影響，這些因素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。有關這些風險和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2016年12月31日止年度的10-K表格，該表格將於今日晚些時候提交給SEC。 Regeneron不承擔任何公開更新任何前瞻性聲明的義務，無論是因為新資訊、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 on our financial results press releases, 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財務指標。有關我們使用非GAAP財務指標的資訊以及這些指標與GAAP的調節表，請參閱我們的財務表現新聞稿，這些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 further 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其他問題。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。

Thank you, Michael.

謝謝你，麥可。

A very good morning to everyone. I echo Michael's sediment here on the East Coast. I hope you are all safe from the storm.

各位早安。我和麥可一樣，也感受到了東岸的風暴帶來的衝擊。希望大家都能平安度過這場風暴。

2016 was an important and eventful year from Regeneron, and one where we received significant progress on the commercial, research and development fronts. We currently have eight late-stage Phase 3 programs, and a total of 16 product candidates in clinical development.

2016年對Regeneron來說是重要且意義非凡的一年，我們在商業化、研發方面都取得了顯著進展。目前我們有8個處於後期III期臨床試驗階段的項目，以及總共16個處於臨床開發階段的候選產品。

Our science-driven approach has remained unchanged. As we look at 2017, we remain confident that we are well-positioned to reap the benefits of our long-standing scientific endeavors. We expect two new major drug approvals in the United States this year. First, we are anticipating regulatory action in the United States at the end of March for Dupilumab or Dupixent. Our breakthrough IL-4/IL-13 blocker for moderate to severe atopic dermatitis. We believe that if approved, Dupixent will change the way doctors are able to treat their moderate to severe atopic dermatitis patients.

我們始終堅持以科學為導向的理念。展望2017年，我們依然充滿信心，相信我們已做好充分準備，收穫長期科研努力的成果。我們預計今年將有兩款重磅新藥在美國核准。首先，我們預期Dupilumab（商品名Dupixent）將在3月底在美國獲得監管部門的批准。 Dupixent是我們突破性的IL-4/IL-13阻斷劑，用於治療中度至重度異位性皮膚炎。我們相信，如果Dupixent獲得批准，將徹底改變醫生治療中重度異位性皮膚炎患者的方式。

Secondly, we expect regulatory action by the FDA for Sarilumab, our IL-6 receptor antibiotic for rheumatoid arthritis. We're happy to report that just last week Sarilumab, now also known by its brand name Kevzara, was approved by Health Canada.

其次，我們期待美國食品藥物管理局（FDA）對我們用於治療類風濕性關節炎的IL-6受體抗生素Sarilumab採取監管行動。我們很高興地宣布，就在上週，Sarilumab（現在也以其商品名Kevzara為人所知）已獲得加拿大衛生部的批准。

Strong preclinical data, as well as our positive findings from our studies in atopic dermatitis, asthma, and nasal polyps indicate that IL-4 and IL-13 signaling is a key pathway driving many allergic conditions and diseases. You will hear further details from George about our Dupilumab development program.

強有力的臨床前數據，以及我們在異位性皮膚炎、氣喘和鼻息肉研究中取得的積極成果表明，IL-4 和 IL-13 訊號通路是驅動多種過敏性疾病的關鍵通路。您將從 George 那裡了解更多關於我們 Dupilumab 開發專案的資訊。

We are keenly focused on ensuring that the anticipated Dupixent launch in the atopic dermatitis indication is a success by all metrics. I personally, in addition to the teams at Regeneron and Sanofi, have engaged in fruitful discussions with payers. We remain optimistic that Dupixent, the breakthrough product, will receive good formulaic coverage when approved for the treatment of moderate to sever atopic dermatitis.

我們正全力確保Dupixent在異位性皮膚炎適應症上的預期上市能取得全面成功。我自己以及Regeneron和Sanofi的團隊都與付款者進行了富有成效的討論。我們仍然樂觀地認為，Dupixent這款突破性產品在獲準用於治療中重度異位性皮膚炎後，將獲得良好的醫療覆蓋範圍。

We will also be working rapidly to advance Dupilumab in asthma. If the read out from the ongoing Phase 3 study is positive, we anticipate making a US regulatory submission in the fourth quarter of this year. Combined with our other ongoing and planned studies of Dupilumab and allergic diseases, we believe that this product candidate has the potential to gain approval in multiple allergic disorders.

我們也將加快推進度普利尤單抗在氣喘領域的應用。如果正在進行的3期臨床試驗結果積極，我們預計今年第四季向美國監管機構提交申請。結合我們正在進行和計劃進行的其他度普利尤單抗治療過敏性疾病的研究，我們相信該候選產品有望獲準用於治療多種過敏性疾病。

EYLEA remains an important product for the Company. We continue to defend and extend the franchise by focusing on new indications, like non-proliferative diabetic retinopathy, and combination studies with Ang2. Bob Terifay will discuss this further on the call. For the full year of 2017, we expect US EYLEA net sales year-over-year percentage growth to be in the single digits. As we further diversify our product-related revenues stream, we do not plan to provide EYLEA product sales guidance after 2017.

EYLEA 仍然是公司的重要產品。我們將繼續鞏固並拓展此產品線，重點關注新的適應症，例如非增殖性糖尿病視網膜病變，以及與 Ang2 的聯合用藥研究。 Bob Terifay 將在電話會議上對此進行更詳細的討論。我們預計 2017 年全年美國 EYLEA 淨銷售額年增率將達到個位數。隨著我們進一步實現產品相關收入來源多元化，我們計劃在 2017 年後不再提供 EYLEA 產品銷售指引。

Turning to Praluent. This has been a terrific week for patients with high LDL cholesterol. First, the LDL hypothesis was validated for PCSK9 inhibitors, with positive outcomes data reported by a competitor. We look forward to completing our own outcome study towards the end of this year.

接下來談談Praluent。對高LDL膽固醇患者來說，這週可謂喜訊連連。首先，PCSK9抑制劑的LDL假說得到了驗證，一家競爭對手公佈了積極的療效數據。我們期待在今年年底前完成我們自己的療效研究。

Second, just yesterday evening, we were granted our request for a stay of the injunction pending the appeal. Praluent will continue to be available to patients in the United States. Meaning that patients and doctors will continue to be able to choose the best PCSK9 inhibitor for their needs. Including the use of a low 75 mg option which only Praluent provides.

其次，就在昨晚，我們提出的暫緩執行禁令的請求已獲批准，等待上訴結果。 Praluent將繼續在美國銷售，這意味著患者和醫生將繼續能夠根據自身需求選擇最合適的PCSK9抑制劑，包括Praluent獨有的75毫克低劑量方案。

We remain committed to ensuring that patients who can benefit from Praluent will continue to have access to this innovative therapy. As for the ongoing litigation, we strongly believe that the controlling law and facts support our position that Amgen's asserted patent claims are invalid. We look forward to pursuing our appeal over the coming months.

我們始終致力於確保能夠從Praluent中獲益的患者繼續獲得這項創新療法。至於正在進行的訴訟，我們堅信相關法律和事實支持我們的立場，即安進公司所主張的專利權無效。我們期待在未來幾個月內繼續推進上訴。

Finally, before I turn it over to George, I want to note that we have started to recognize students in our first year as sponsors of the 75-year-old Science Talent Search, the most prestigious high school talent competition. As many of you know, this program was previously sponsored by Intel and before that by Westinghouse. Over the last few weeks we were excited to recognize our first group of 300 Regeneron science talent search scholars and 40 finalists. We believe programs like this are essential to ensuring a strong science talent pipeline for generations to come.

最後，在把發言權交給喬治之前，我想提一下，我們第一年就開始表彰那些贊助了擁有75年歷史的科學人才選拔賽（Science Talent Search）的學生。這項賽事是高中生中最負盛名的才藝競賽。如大家所知，這項賽事先前由英特爾贊助，再之前則由西屋電氣贊助。在過去的幾周里，我們很高興地表彰了首批300名Regeneron科學人才選拔賽獎學金得主和40名決賽入圍者。我們相信，像這樣的計畫對於確保未來幾代人擁有強大的科學人才儲備至關重要。

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

接下來，我想把電話交給喬治。

Thank you, Len.

謝謝你，Len。

A very good morning to everyone who has joined us today.

各位早安！

I would like to begin with the Dupixent, our IL-4/IL 13 blocker. I share Len's excitement about this molecule and its potential use not only in moderate to severe atopic dermatitis, but also in various other allergic conditions. As Len mentioned, Dupixent is on track towards the end of March for an expected regulatory approval in the United States for moderate to severe atopic dermatitis in adults. You will hear more about our ongoing launch preparations from Bob Terifay.

我想先談談我們的IL-4/IL-13阻斷劑Dupixent。我和Len一樣，對這種分子及其在治療中重度異位性皮膚炎以及其他多種過敏性疾病方面的潛在應用感到興奮。正如Len所提到的，Dupixent預計在3月底獲得美國監管機構的批准，用於治療成人中度重度異位性皮膚炎。關於我們正在進行的上市準備工作，Bob Terifay會向您詳細介紹。

In the fourth quarter of 2016, the marketing authorization application for Dupixent in this indication was accepted for review by the European Medicines Agency or the EMA. Dupixent has received breakthrough designation in both the adult and pediatric atopic dermatitis indications. In the latter, we expect to initiate a Phase 3 study in adolescent patient between the ages of 12 and 17 in the first quarter. In the second quarter another phase-three study in younger patients between the ages of 6 and 11.

2016年第四季度，Dupixent用於該適應症的上市許可申請已獲歐洲藥品管理局（EMA）受理。 Dupixent已獲得成人和兒童異位性皮膚炎適應症的突破性療法認定。在兒童異位性皮膚炎適應症方面，我們預計在第一季啟動一項針對12至17歲青少年患者的3期臨床試驗。第二季度，我們將啟動另一項針對6至11歲兒童患者的3期臨床試驗。

Scientific evidence indicates that the IL-4/IL 13 pathway is essential not just in atopic dermatitis, but also in a wide spectrum of allergic diseases. With that hypothesis, we're exploring the use of Dupilumab in multiple allergic conditions. Let me begin with asthma.

科學證據表明，IL-4/IL-13路徑不僅在異位性皮膚炎中至關重要，而且在多種過敏性疾病中也發揮重要作用。基於這個假設，我們正在探索度普利尤單抗在多種過敏性疾病中的應用。首先，我想談談氣喘。

Positive data from a previously-reported first pivotal study of Dupilumab in persistent uncontrolled asthma, which have also published in the New England Journal of Medicine, demonstrated that in all patients, regardless of their allergic classification, treatment with Dupilumab resulted in improvement in both lung function, as measured in sPD-1, and exacerbations.

先前報告的 Dupilumab 治療持續性未控制氣喘的首個關鍵性研究的積極數據（也發表在《新英格蘭醫學雜誌》上）表明，無論患者的過敏分類如何，Dupilumab 治療都能改善所有患者的肺功能（以 sPD-1 衡量）和哮喘急性發作情況。

In the overall population, patients treated with the 300 mg every-other-week dose had a 15% improvement over placebo in the sPD-1 measure and a 75 % reduction in exacerbations. The most common adverse event associated with treatment in this study was injection site reaction.

所有受試者中，接受每隔一週300毫克劑量治療的患者，其sPD-1指標較安慰劑組改善15%，病情加重次數減少75%。本研究中最常見的治療相關不良事件是注射部位反應。

In our opinion, efficacy of all comers rather than only in those with allergic classifications could be an important differentiating feature of the product profile. Particularly in competitive indications such as asthma. As a reminder, the approved biologics in asthma are indicated only for patients with an allergic classification.

我們認為，對所有患者而非僅限於過敏體質患者均有效，可能是該產品的重要差異化特徵，尤其是在氣喘等競爭激烈的適應症領域。需要提醒的是，目前核准的氣喘生物製劑僅適用於過敏體質患者。

Our large second-pivotal study, LIBERTY ASTHMA QUEST, a Phase 3 study in adults and adolescent patients with uncontrolled persistent asthma, is fully enrolled. We expect to report top-line data later this year, with a regulatory submission to follow in the fourth order. Additionally, in the first quarter 2017, we expect to initiate a Phase 3 study of uncontrolled persistent asthma in pediatric patients between the ages of 6 and 11.

我們的大型第二項關鍵性研究 LIBERTY ASTHMA QUEST 是一項針對成人和青少年未控制持續性氣喘患者的 III 期臨床試驗，目前已完成全部受試者招募。我們預計將於今年稍後公佈初步數據，並於第四季提交監管申請。此外，我們預計將於 2017 年第一季啟動一項針對 6 至 11 歲兒童未控制持續性氣喘患者的 III 期臨床試驗。

Following quickly behind the atopic dermatitis and asthma indications are additional indications for Dupilumab. These include nasal polyps, where we're currently enrolling patients in two separate Phase 3 studies. The next indication is eosinophilic esophagitis, where we expect a report in the first half of 2017 top-line data from our Phase 2 study. We continue to explore the role of Dupilumab and new indications and plan to initiate a Phase II study in Dupilumab in food allergies in the second half 2017.

繼異位性皮膚炎和氣喘適應症之後，度普利尤單抗的其他適應症也即將出現。其中包括鼻息肉，我們目前正在進行兩項獨立的3期臨床試驗，招募患者參與治療。下一個適應症是嗜酸性食道炎，我們預計2017年上半年公佈2期臨床試驗的主要數據。我們將繼續探索度普利尤單抗的作用及其新的適應症，並計劃於2017年下半年啟動一項度普利尤單抗治療食物過敏的2期臨床試驗。

We are pleased with the advances in our late-stage pipeline. Just last week, Sarilumab our IL-6 receptor antibody, now known as Kevzara, was approved by Health Canada for the treatment of rheumatory arthritis. Kevzara is filled and finished at Sanofi's facility in Le Trait, France. As we've mentioned before, this facility is being inspected this quarter. Subject to a successful completion of the inspection, we plan to resubmit the BLA for Sarilumab to the FDA in the first quarter, with an expected two-month review cycle.

我們對後期研發管線的進展感到欣喜。就在上週，我們的IL-6受體抗體Sarilumab（現更名為Kevzara）獲得了加拿大衛生部的批准，用於治療類風濕性關節炎。 Kevzara在賽諾菲位於法國勒特雷的工廠進行填充和包裝。正如我們之前提到的，該工廠正在接受本季的檢查。如果檢查順利通過，我們計劃在第一季向美國食品藥物管理局（FDA）重新提交Sarilumab的生物製品許可申請（BLA），預計審批週期為兩個月。

Our Phase 3 NGF Antibody program with Fasinumab is also advancing. We, along with our collaborator Teva, look forward to initiating additional Phase 3 studies in both osteoarthritis pain as well as the chronic lower back indication. REGN2222, our program for respiratory syncytial virus, is also moving ahead. We expect the ongoing study to be completed by the end of the year.

我們與 Fasinumab 合作進行的 NGF 抗體 III 期臨床試驗也穩步進行。我們與合作夥伴 Teva 期待啟動更多針對骨關節炎疼痛和慢性下背痛適應症的 III 期臨床試驗。此外，我們針對呼吸道合胞病毒的 REGN2222 計畫也在穩步推進。我們預計該項正在進行的研究將於年底前完成。

Moving now to our EYLEA. We are conducting two Phase 2 studies of EYLEA in combination with Nesvacumab, our antibody to Ang2. Both these studies, one each in wet AMD and DME, are fully enrolled. The efficacy and safety data from both of these studies will be analyzed at 36 weeks.

接下來談談我們的EYLEA。我們正在進行兩項EYLEA合併Nesvacumab（一種抗Ang2抗體）的II期臨床試驗。這兩項試驗分別針對濕性AMD和DME，目前都已完成病患招募。我們將對這兩項試驗的療效和安全性數據進行36週的分析。

While there is greater preclinical support for Ang2 compared to our PDGF program, which we are no longer pursuing as we've mentioned before, EYLEA sets a very high bar for efficacy in these disease indications. We look forward to seeing the data from our Phase 2 studies with Ang2 in the second half this year.

雖然Ang2相比我們之前提到的已停止的PDGF項目擁有更充分的臨床前支持，但EYLEA在這些疾病適應症方面樹立了極高的療效標竿。我們期待今年下半年看到Ang2二期臨床試驗的數據。

Panorama, our Phase 3 study of EYLEA in patients with non-proliferative diabetic retinopathy without diabetic macular edema, continues to enroll patients.

Panorama 是我們正在進行的針對非增殖性糖尿病視網膜病變（不伴隨糖尿病性黃斑水腫）患者的 EYLEA 的 3 期研究，目前仍在招募患者。

Turning now to Praluent, our PCSK9 antibody for lowering LDL cholesterol. The ODYSSEY OUTCOMES trial, our 18,000 patient cardiovascular outcome study of Praluent, is ongoing. This is an event-driven study, and we expect it to be completed by the end of 2017. We expect the positive outcomes data will increase the uptick PCSK9 antibodies in appropriate patients.

現在來說說Praluent，一種用來降低低密度脂蛋白膽固醇的PCSK9抗體。我們正在進行一項名為ODYSSEY OUTCOMES的試驗，這是一項針對18,000名患者的Praluent心血管結局研究，目前正在進行中。這是一項以事件為導向的研究，我們預計在2017年底完成。我們預期正面的結局數據將促使PCSK9抗體在適當的患者群體中得到更廣泛的應用。

We are pleased with the progress we are making with our immuno oncology portfolio. REGN2810, our PD-1 antibody, continues to advance. We are currently enrolling patients in a potentially pivotal study in cutaneous granular cell carcinomas.

我們對免疫腫瘤產品組合的進展感到滿意。我們的PD-1抗體REGN2810正在持續推進。目前，我們正在招募患者參與一項針對皮膚顆粒細胞癌的潛在關鍵性研究。

In addition, we also plan to initiate in the first of the year, a clinical study in basal cell carcinoma. In the on dermal cancers, we plan to initiate in the first half of the year a clinical study for our PD-1 antibody in non-small cell lung cancer. Our second checkpoint inhibitor, REGN3767, an antibody to LAG-3, has also entered the clinic. We will be studying it both as monotherapy as well as in combination with our PD-1 antibody.

此外，我們計劃於年初啟動一項針對基底細胞癌的臨床研究。在皮膚癌方面，我們計劃在上半年啟動一項針對非小細胞肺癌的PD-1抗體臨床研究。我們的第二個免疫檢查點抑制劑REGN3767（一種針對LAG-3的抗體）也已進入臨床試驗階段。我們將研究其單藥治療以及與PD-1抗體合併治療的療效。

Let me also update you on progress with our bi-specific platform. Our lead program, a CD20 by CD3 antibodies, currently in the clinic both as monotherapy and also in combination with our PD-1 antibody. We believe we now have a dosing schedule for the CD20 by CD3 by specific antibody, and look forward to expanding the number of patients treated with that dosing regimen.

我還想向大家報告我們雙特異性抗體平台的進展。我們的主要項目是一種CD20/CD3雙特異性抗體，目前正在進行臨床試驗，既有單藥治療，也有與PD-1抗體合併治療。我們相信現在已經確定了CD20/CD3雙特異性抗體的給藥方案，並期待擴大使用該給藥方案治療的患者群體。

Lastly, I am happy to report that REGN2477, our Activin A antibody for the treatment of the rare disease fibrodysplasia ossificans progressiva, or FOP, is completing a Phase 1 study in healthy volunteers. Then we expect to begin a Phase 2 trial in FOP patients later this year. We also recently initiated a combination Phase 1 trial in healthy volunteers of REGN2477 with Trevogrumab, our antibody of GDF8 for skeletal muscle diseases.

最後，我很高興地報告，我們用於治療罕見疾病進行性骨化性纖維發育不良症（FOP）的Activin A抗體REGN2477，已完成一項針對健康志願者的I期臨床試驗。我們預計今年稍後啟動一項針對FOP患者的II期臨床試驗。此外，我們近期也啟動了一項REGN2477合併Trevogrumab（一種用於治療骨骼肌疾病的GDF8抗體）的I期臨床試驗，受試者為健康志願者。

Before I turn it over to Bob Terifay want to add my congratulations to the 300 Regeneron scholars and 40 Regeneron finalists in the Science Talent Search. But also add congratulations to every high school student who did a science project and applied. These are our scientific leaders of the future who we hope are going to change and save our world.

在把發言權交給鮑伯·特里費之前，我想向300位獲得再生元獎學金的同學和40位入圍科學人才選拔賽決賽的同學表示祝賀。同時，我也要祝賀每一位參與科學計畫並提交申請的高中生。他們是我們未來的科學領導人物，我們希望他們能夠改變並拯救我們的世界。

With that, when let me turn the call over to Bob Terifay.

那麼，現在讓我把電話交給鮑伯·特里費。

Thank you, George.

謝謝你，喬治。

Good morning, everyone.

各位早安。

Fourth quarter US EYLEA, or Aflibercept, net sales grew 15% year over year. Net US EYLEA sales in the fourth quarter were $858 million, and full-year 2016 sales were $3.23 billion. Net ex-US EYLEA sales in the fourth quarter were $496 million, which represents 20% growth year over year unadjusted for currency fluctuations.

美國安麗公司（EYLEA，商品名阿柏西普）第四季淨銷售額年增15%。第四季美國安利淨銷售額為8.58億美元，2016年全年銷售額為32.3億美元。第四季美國以外地區安利淨銷售額為4.96億美元，未經匯率調整後較去年同期成長20%。

Net ex-US EYLEA full-year 2016 sales were $1.87 billion. In 2016, global net sales of EYLEA exceeded $5 billion. EYLEA is the market leading product among FDA-approved VEGF agents for all of its approved indications in the United States. EYLEA will continue to be a major revenue driver for Regeneron over the years to come.

2016年，除美國以外，EYLEA的全年淨銷售額為18.7億美元。 2016年，EYLEA的全球淨銷售額超過50億美元。在美國，EYLEA是所有核准適應症中，FDA核准的VEGF製劑的市場領先產品。未來幾年，EYLEA將繼續成為Regeneron的主要收入來源。

Our quarter-over-quarter EYLEA sales growth has slowed. Reflecting normal market dynamics from a more mature product that has been on the market for over five years with no price increase since launch. We continue to focus our promotional efforts in the clinical efficacy and safety of EYLEA and our development efforts of potential new indications in combinations. The next potential driver for EYLEA growth could be an indication for non-proliferative diabetic retinopathy, which is currently in Phase 3 development. Our fixed combination program for EYLEA and Nesvacumab, our angiopoietin2 inhibitor, is currently in Phase 2 clinical development.

EYLEA的季度環比銷售成長放緩。這反映了市場正常的動態，畢竟這是一款上市五年多、價格一直未曾上漲的成熟產品。我們將繼續把推廣重點放在EYLEA的臨床療效和安全性上，以及合併用藥潛在新適應症的研發。 EYLEA的下一個潛在成長動力可能是非增殖性糖尿病視網膜病變適應症，目前正處於III期臨床試驗階段。 EYLEA與血管生成素2抑制劑Nesvacumab的固定劑量複方製劑計畫目前正處於II期臨床試驗階段。

Turning now to Praluent or alirocumab. As reported by Sanofi, net sales in the fourth quarter were $41 million worldwide. with the US accounting for $33 million of the total. Full-year 2000 net sales were $116 million, with the US accounting for $94 million. We are pleased that the Federal Court has suspended the injunction on Praluent sales, marketing and manufacturing. Therefore, we will continue our efforts to grow Praluent sales and alleviate reimbursement roadblocks.

現在我們來談談Praluent（阿利西尤單抗）。根據賽諾菲公司報告，第四季全球淨銷售額為4,100萬美元，其中美國市場貢獻了3,300萬美元。 2000年全年淨銷售額為1.16億美元，其中美國市場貢獻了9,400萬美元。我們很高興地看到，聯邦法院已暫停Praluent銷售、市場推廣和生產的禁令。因此，我們將持續努力提升Praluent的銷售額，並消除健保報銷方面的障礙。

Remember, Praluent is the only PCSK9 inhibitor that offers a low-dose option. Most of our sales are for the low dose 75 mg dosage form. Outside of the United States, Praluent is approved in 45 countries. Reimbursement decisions by individual country, region and institutional pricing and reimbursement authorities are gradually evolving.

請記住，Praluent 是唯一提供低劑量選擇的 PCSK9 抑制劑。我們的大部分銷售額都來自 75 毫克低劑量劑型。除美國外，Praluent 已在 45 個國家/地區獲得批准。各國和機構的定價和報銷政策正在逐步調整。

We are currently preparing for the potential approval and launch of Dupixent, or Dupilumab, with a FDA PDUFA date of March 29, 2017. Sanofi Genzyme and Regeneron have fully hired and trained our field teams. At launch, our field teams will call on 4,500 dermatologists and 1,200 allergists who currently prescribe biologic therapies. These are the physicians who will most likely be comfortable with prescribing a biologic for atopic dermatitis.

我們目前正積極準備Dupixent（或稱為Dupilumab）的潛在核准上市，FDA的處方藥使用者付費法案（PDUFA）核准日期為2017年3月29日。賽諾菲健贊和再生元已完成我們銷售團隊的招募和培訓。上市初期，我們的銷售團隊將拜訪目前開立生物製劑處方的4,500名皮膚科醫師和1,200名過敏科醫師。這些醫生很可能樂於為異位性皮膚炎患者開立生物製劑。

We estimate that approximately 300,000 atopic dermatitis patients have exhausted all approved therapies and have failed, or are unable to tolerate, unapproved use of immunosuppressant therapies. We have been working with payers to ensure that these patients have access to treatment. As Len mentioned, our discussions with payers are proceeding well. We're optimistic that we can work productively to ensure that patients get appropriate and rapid access to this breakthrough product after approval.

我們估計，約有30萬名異位性皮膚炎患者已用盡所有核准療法，且對未經批准的免疫抑制劑療法無效或無法耐受。我們一直在與支付方合作，以確保這些患者能夠獲得治療。正如Len所提到的，我們與支付方的討論進展順利。我們樂觀地認為，在產品核准後，我們可以有效地合作，確保患者能夠及時、適當地獲得這種突破性產品。

In anticipation of early demand, we have established a Reimbursement Access Services and Patient Support Center, which will be ready to help patients from day one of launch. Our pre-commercialization efforts have been focused on educating physicians, patients, and payers on the unmet medical need in moderate to severe uncontrolled atopic dermatitis. Its devastating impact on patients' lives and the role of chronic underlying systemic inflammation and its etiology. This unbranded education has been provided at major medical meetings, through digital media, and through print media.

為因應早期需求，我們已設立報銷准入服務和病患支援中心，從產品上市之日起即可為病患提供協助。在產品上市前，我們致力於向醫生、患者和支付方普及中重度未控制異位性皮膚炎的未滿足醫療需求，以及該疾病對患者生活的嚴重影響，並探討慢性潛在系統性發炎及其病因。我們已在大型醫學會議、數位媒體和印刷媒體上開展了這些非品牌化的教育活動。

Our launch materials and programs are preliminarily prepared, pending approval and receipt of our final label. We filed a regulatory application for Dupixent in the EU in the fourth quarter 2016. Pending a favorable inspection in the first quarter of 2017 of Sanofi's fill-and-finish facility in Le Trait, France, we intend to quickly refile our Kevzara, or Sarilumab BLA, with the FDA with potential approval in the second quarter of 2017. Sanofi Genzyme and Regeneron have hired and trained our field teams, who will call on over 6,000 rheumatologists responsible for the vast majority of biologics prescriptions for rheumatoid arthritis.

我們的上市資料和項目已初步準備就緒，目前正在等待最終標籤的批准和接收。我們於2016年第四季在歐盟提交了Dupixent的監管申請。如果賽諾菲位於法國勒特雷的灌裝和包裝工廠在2017年第一季順利通過檢查，我們將盡快向美國食品藥品監督管理局（FDA）重新提交Kevzara（或Sarilumab）的生物製品許可申請（BLA），並有望在2017年第二季獲得批准。賽諾菲健贊和再生元已聘請並培訓了我們的市場推廣團隊，他們將拜訪超過6000名風濕病專科醫生，這些醫生負責開具絕大多數用於治療類風濕性關節炎的生物製劑處方。

As with Dupixent, we have also been working with payers to ensure that patients have access to Kevzara. We have established a Reimbursement Access Services and Patient Support Center pending regulatory approval. Our pre-commercialization efforts have focused on demonstrating the essential role of interleukin-6 in rheumatoid arthritis to rheumatologists. Our preparation for potential launch is in place, pending approval and final labeling.

與Dupixent一樣，我們也一直在與支付者合作，確保患者能夠獲得Kevzara。我們已設立報銷准入服務和病患支援中心，目前正在等待監管部門的批准。在上市前，我們的工作重點是向風濕病學家證明白細胞介素-6在類風濕性關節炎中的關鍵作用。我們已做好上市準備，只待獲得批准並完成最終標籤確定。

Kevzara achieved its first approval in Canada earlier in 2017. The European Marketing Authorization Application, or MAA, for Kevzara is currently under review by the EM, with a potential decision on the application expected in mid-2017.

Kevzara 於 2017 年初在加拿大獲得首次批准。 Kevzara 的歐洲上市許可申請 (MAA) 目前正在接受歐洲藥品管理局 (EM) 的審查，預計將於 2017 年年中做出決定。

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.

謝謝你，鮑伯。

Good morning to everyone.

大家早安。

Overall, we delivered solid fourth-quarter financial results. In the fourth quarter of 2016, we earned $3.04 per diluted share from non-GAAP net income of $343 million (sic - see Press Release "$353m"). For the full-year 2016, we earned $11.32 per diluted share from non-GAAP net income of $1.32 billion. This represents a year-over-year increase in non-GAAP diluted EPS in net income of 36% and 37%, respectively, for the fourth quarter. and a year-over-year increase in non-GAAP diluted EPS in net income of 39% and 40%, respectively, for the full year of 2016.

整體而言，我們第四季財務業績穩健。 2016年第四季，我們實現非GAAP淨利3.43億美元（原文誤寫為3.53億美元，參見新聞稿），每股攤薄收益為3.04美元。 2016年全年，我們實現非GAAP淨利13.2億美元，每股稀釋收益為11.32美元。第四季非GAAP攤薄後每股盈餘較去年同期成長36%，全年非GAAP攤薄後每股盈餘較去年同期成長37%；2016年全年非GAAP攤薄後每股盈餘較去年同期成長39%，全年非GAAP攤薄後每股盈餘較去年同期成長40%。

Regeneron's fourth-quarter and full-year 2016 non-GAAP net income primarily excludes non-cash year base compensation expense, and includes the income tax effect of non-GAAP reconciling items. A full reconciliation of GAAP to non-GAAP earnings is set forth in our earnings release. All of the financial guidance mentioned on this call today, and in our fourth quarter 2016 earnings release issued earlier this morning, assumes that Praluent went will remain on the market throughout 2017.

Regeneron 2016 年第四季及全年非 GAAP 淨利主要剔除了非現金年度基本薪資支出，但包含了非 GAAP 調整項目的所得稅影響。 GAAP 與非 GAAP 收益的完整調整表已在我們的獲利報告中列出。今天電話會議以及今天稍早發布的 2016 年第四季獲利報告中提及的所有財務預測均基於 Praluent 將在 2017 年全年繼續上市的假設。

Total revenues in the fourth quarter of 2016 were $1.23 billion and $4.86 billion for the full year 2016. Which represented year-over-year growth of 12% for the three months and 18% for the full year. Net product sales were $863 million in the fourth quarter of 2016 and $3.34 billion for the full year 2016. Compared to $750 million in the fourth quarter of 2015 and $2.69 billion for the full year of 2015.

2016年第四季總營收為12.3億美元，全年總營收為48.6億美元，年增12%（第四季）及18%（全年）。 2016年第四季淨產品銷售額為8.63億美元，全年淨產品銷售額為33.4億美元，而2015年第四季淨產品銷售額為7.5億美元，全年淨產品銷售額為26.9億美元。

EYLEA net products sales in the United States were $858 million in the fourth quarter 2016, and $3.32 billion for the full year 2016. Compared to $746 million in the fourth quarter of 2015, and $2.68 billion for the full year of 2015. Which represented a increase of 15% and 24%, respectively.

2016年第四季，安禮在美國的淨產品銷售額為8.58億美元，全年為33.2億美元。相比之下，2015年第四季為7.46億美元，全年為26.8億美元，分別成長了15%和24%。

During the fourth quarter of 2016, EYLEA experienced a small increase in US distributor inventory levels, as compared to the third quarter of 2016. Yet remained within our normal one- to two-week target range. Additionally, we experienced a slight increase in our EYLEA gross to net percentage as a result of an increase in the proportion of Medicaid patients treated with EYLEA.

2016年第四季度，與2016年第三季相比，EYLEA在美國分銷商的庫存水準略有上升，但仍在我們正常的1至2週目標範圍內。此外，由於使用EYLEA治療的醫療補助（Medicaid）患者比例增加，EYLEA的毛利率也略有上升。

Ex-US EYLEA sales were $496 million in fourth quarter of 2016, as compared to $413 million in the fourth quarter of 2015 representing a 20% increase on a reported basis. Ex-US EYLEA sales for the full year of 2016 were $1.87 billion compared to $1.41 billion for 2015, representing a 33% increase on a reported basis. Sales growth on an operational or constant currency basis were consistent with our reported sales growth.

2016年第四季度，安禮（EYLEA）在美國以外的銷售額為4.96億美元，而2015年第四季為4.13億美元，按報告數據計算成長20%。 2016年全年，安禮（EYLEA）在美國以外的銷售額為18.7億美元，而2015年為14.1億美元，以報告數據計算成長33%。按營運匯率或固定匯率計算的銷售成長與報告的銷售成長一致。

In the fourth quarter of 2016, Regeneron recognized $165 million from our share of net profits from EYLEA sales outside of the United States and $649 million for the full year of 2016. Total Bayer collaboration revenue for the fourth quarter of 2016 was $181 million and $744 million for the full year of 2016.

2016 年第四季度，Regeneron 從美國以外地區 EYLEA 的銷售淨利潤中確認了 1.65 億美元的份額，2016 年全年確認了 6.49 億美元的份額。 2016 年第四季與拜耳的合作總收入為 1.81 億美元，2016 年全年為 7.44 億美元。

Total Sanofi collaboration revenue was $131 million for the fourth quarter of 2016 and $659 million for the full year of 2016. 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 commercialization of antibodies.

2016 年第四季度，賽諾菲合作總營收為 1.31 億美元；2016 年全年，賽諾菲合作總營收為 6.59 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，以及我們應佔的抗體商業化損益份額。

In the fourth quarter of 2016, our share of losses in connection with the commercialization of Praluent, in pre-commercialization activities and costs in connection with Kevzara and Dupixent, was $126 million and was a loss of $459 million for the full year of 2016. This can be found in Table 4 of our earnings release. Netted within these losses were the global sales of Praluent for the fourth quarter of 2016, as recognized by our partner Sanofi, of $41 million and $116 million for the full year of 2016.

2016年第四季，我們因Praluent商業化、商業化前活動以及Kevzara和Dupixent相關成本而產生的虧損份額為1.26億美元，2016年全年虧損總額為4.59億美元。詳情請見我們的獲利報告表4。上述虧損中已扣除我們的合作夥伴賽諾菲確認的2016年第四季Praluent全球銷售額4,100萬美元以及2016年全年銷售額1.16億美元。

Turning now to expenses. Non-GAAP R&D expenses were $404 million for the fourth quarter of 2016, and $1.64 billion for the full year. Our non-GAAP unreimbursed R&D expense, which is calculated as the total non-GAAP R&D expenses less R&D reimbursements from our collaborators, was $240 million for the three months ended December 31, 2016, and $882 million for the full year of 2016. Our press release includes all the information, as required, to calculate unreimbursed non-GAAP R&D expenses.

接下來談談費用。 2016年第四季非GAAP研發費用為4.04億美元，全年為16.4億美元。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款項）在截至2016年12月31日的三個月內為2.4億美元，2016年全年為8.82億美元。我們的新聞稿包含了計算未報銷非GAAP研發費用所需的所有資訊。

I would like to note that our non-GAAP unreimbursed R&D expenses came in below our 2016 guidance. Due to less spending than forecasted in our Sarilumab and Dupilumab programs and lower operating expenses than forecasted in our Rensselaer manufacturing facility. For 2017, we would like to reiterate our previously provided guidance for non-GAAP unreimbursed R&D to be in the range of $950 million to $1.025 billion.

我想指出，我們2016年的非GAAP未報銷研發費用低於預期。這主要是由於Sarilumab和Dupilumab計畫的支出低於預期，以及倫斯勒生產基地的營運費用低於預期。對於2017年，我們重申先前提供的非GAAP未報銷研發費用預期，即在9.5億美元至10.25億美元之間。

Next, non-GAAP SG&A expenses were $252 million for the fourth quarter 2016 and $947 million for the full year of 2016. Non-GAAP SG&A came in below 2016 guidance. Largely due to lower-than-expected fourth quarter spending on Praluent, as well as the delayed Kevzara launch. We continue to expect non-GAAP SG&A expense in 2017 to be in the range of $1.175 billion and $1.250 billion. The increase in our forecasted 2017 non-GAAP SG&A expense is primarily driven by the anticipated launches of Kevzara and Dupixent, as well as and increase in commercialization-related expenses for EYLEA.

其次，2016年第四季非GAAP銷售、管理及行政費用為2.52億美元，全年為9.47億美元。非GAAP銷售、管理及行政費用低於2016年預期，主要原因是第四季Praluent的支出低於預期，以及Kevzara上市延遲。我們仍預計2017年非GAAP銷售、管理及行政費用將介於11.75億美元至12.5億美元之間。我們預測2017年非GAAP銷售、管理及行政費用增加的主因是Kevzara和Dupixent的預期上市，以及安永商業化相關費用的增加。

Sanofi reimbursement of Regeneron commercialization related expense, as a line item found within Sanofi collaboration revenue, was $97 million fourth quarter 2016 and $322 million for the full year of 2016. We expect Sanofi reimbursement of Regeneron commercialization-related expenses in 2017 to be in the range of $400 million and $450 million.

賽諾菲對Regeneron商業化相關費用的報銷（作為賽諾菲合作收入中的一個項目）在2016年第四季為9700萬美元，2016年全年為3.22億美元。我們預計賽諾菲在2017年Regeneron商業化相關費用的報銷將在4億美元至4.5億美元之間。

Turning now to taxes. Our effective tax rate for the fourth quarter and full year of 2016 was approximately 26% and 33%, respectively, as compared to approximately 32% and 48% for the fourth quarter and full year of 2015. As a reminder, due to the adoption of Accounting Standards Update 2016-09, the utilization of excess tax benefits in connection with employee exercises of stock options, is now reflected in our effective tax rate. These deductions, as well as a change in geographic mix of earnings, were the primary drivers of the reduction in our effective tax rate in 2016 as compared to 2015. For the full year of 2017, we are guiding our effective tax rate to be in the range of 32% to 38%.

現在來說說稅務方面。 2016年第四季和全年的實際稅率分別約為26%和33%，而2015年第四季和全年的實際稅率分別約為32%和48%。需要說明的是，由於採用了2016-09號會計準則更新，員工行使股票選擇權所產生的超額稅收優惠已反映在我們的實際稅率中。這些扣除額以及收益地域分佈的變化是導致2016年實際稅率較2015年下降的主要原因。我們預計2017年全年的實際稅率將在32%至38%之間。

From a cash flow and balance sheet perspective, we ended the fourth quarter 2016 with cash and marketable securities of $1.9 billion. Our capital expenditures for the full year of 2016 were $512 million. As we enter 2017, we expect our capital expenditures levels to be lower than the previous two years, as is reflected in our 2017 guidance of between $375 million and $450 million.

從現金流量及資產負債表角度來看，截至2016年第四季末，我們持有現金及有價證券19億美元。 2016年全年資本支出為5.12億美元。進入2017年，我們預計資本支出水準將低於前兩年，這反映在我們2017年3.75億美元至4.5億美元的支出預期中。

The principal driver of these forecasted lower capital expenditures is decreased spending on the renovation of our Limerick manufacturing facility. Other 2017 capital expenditures include the expansion of our laboratory space within our Tarrytown, New York facilities. And expanding and renovating a portion of our manufacturing facilities at our Rensselaer New York facility.

預計資本支出減少的主要原因是我們在利默里克製造工廠的翻新費用降低。 2017年的其他資本支出包括擴大我們在紐約州塔里敦工廠的實驗室空間，以及擴建和翻新我們在紐約州倫斯勒工廠的部分生產設施。

As highlighted in our third-quarter 2016 conference call, we did take the opportunity in the fourth quarter of 2016 to repurchase, for $401 million, all of our remaining outstanding warrants that we issued in 2011 in connection with our convertible debt. Additionally, our remaining outstanding convertible senior notes were settled on October 1, 2016. In total, our full-year 2016 cash flow statement reflects the use of funds of $656 million in connection with the reduction of outstanding warrants in repayment of the convertible senior notes, which will not recur in 2017.

正如我們在2016年第三季電話會議中所強調的，我們在2016年第四季以4.01億美元的價格回購了所有剩餘的、與2011年發行的可轉換債券相關的未償認股權證。此外，我們剩餘的未償可轉換優先票據已於2016年10月1日結算完畢。總計，我們2016年全年現金流量表反映了用於償還可轉換優先票據的未償認股權證的資金使用量為6.56億美元，該項支出在2017年不會再次發生。

Additionally, in December of 2016, we entered into a purchase agreement with affiliates of BioMed Realty to purchase the properties located at our headquarters in Tarrytown, New York, for $720 million. We intend to finance this acquisition with new lease financing. Where we plan to assign some or all of our rights under the purchase agreement, including the right to take titles to the facility, to an affiliate of Bank of America who will become the legal owner and lessor of the facility. Directly thereafter, we expect to lease the facility from the lessor for five years. With rental payments that are expected to be lower than those under our existing headquarters lease and immediately accretive to Regeneron upon signing the lease.

此外，2016年12月，我們與BioMed Realty的關聯公司簽訂了一項購買協議，以7.2億美元的價格收購位於紐約州塔里敦總部大樓的物業。我們計劃透過新的租賃融資方式為此次收購提供資金。我們計劃將我們在購買協議項下的部分或全部權利（包括取得該物業所有權的權利）轉讓給美國銀行的關聯公司，該公司將成為該物業的合法所有者和出租人。此後，我們預計將從該出租人處租賃該物業五年。預計租金將低於我們現有總部大樓的租金，並在簽署租賃協議後立即增加Regeneron的收益。

At the end of those five years, Regeneron will have a few options. Including extending the lease terms, purchasing the facility at a predetermined amount, or selling the facility to a third party on behalf of the lessor. This transaction is estimated to provide an average after-tax annual cash savings of $21 million during our five-year lease term. We expect to close this transaction in the first quarter of 2017. The contemplated lease financing will not constitute indebtedness for the purposes of our unsecured revolving credit facility, and therefore does not adversely impact our ability to borrow under the credit facility.

五年期滿後，Regeneron將有幾種選擇，包括延長租賃期限、以預定價格購買該設施，或代表出租人將該設施出售給第三方。預計在五年租賃期內，該交易平均每年可為公司節省2,100萬美元的稅後現金。我們預計將於2017年第一季完成該交易。擬議的租賃融資不構成我們無擔保循環信貸額度下的債務，因此不會對我們根據該信貸額度進行借款的能力產生不利影響。

With that, I would like to turn the call back to Michael.

那麼，現在我想把電話轉回給麥可。

Thanks, Bob.

謝謝你，鮑伯。

Operator, we can now open the call for Q&A.

操作員，我們現在可以開始問答環節了。

I would like to remind everybody to please limit yourselves to a single question to allow time for others to ask their questions.

我想提醒大家，請每個問題只提出一個問題，以便給其他人提問的時間。

Operator?

操作員？

Thank you we will now begin the question-and-answer session.

謝謝，現在開始問答。

(Operator Instructions)

（操作說明）

Terence Flynn from Goldman Sachs

高盛的特倫斯·弗林

Hi thank you for taking the question.

您好，感謝您回答這個問題。

Maybe just on the ANG-2 phase 2 trials. If you can remind us if they are blinded are open label? And what is the rationale to wait for the 36 week data instead of reporting the 12 week primary endpoint data? Thanks.

或許只針對ANG-2的第二期臨床試驗。請問這些試驗是雙盲還是開放標籤試驗？另外，為什麼不直接報告12週的主要終點數據，而是等待36週的數據？謝謝。

Well, it is a blinded trial, it is a single injection, either with EYLEA alone or with the various combination arms. And we believe that the 36 week data is going to provide us the best opportunity to really evaluate the value of adding antipode into EYLEA.

這是一項雙盲試驗，採用單次注射，分別單獨使用EYLEA或與其他藥物合併使用。我們相信，36週的數據將為我們提供最佳機會，真正評估在EYLEA中加入對映體的價值。

That is that we designed the study. The primary endpoint is 36 weeks, though.

也就是說，我們設計了這項研究。不過，主要終點是36週。

Geoffrey Porges from Leernick Partners

來自 Leernick Partners 的 Geoffrey Porges

Thank you very much.

非常感謝。

So when you mentioned the weather in New York and I wanted to make sure there wasn't any snow going on in the conference call, so I have to ask you about the guidance for EYLEA.

所以，當你提到紐約的天氣時，我想確認一下電話會議期間是否下雪，所以我必須問你關於EYLEA的指導。

So, you are really guiding to a significant slowdown in 2017, even compared to your growth trajectory in Q4. Could you talk a little bit about the puts and takes in that guidance? Particularly whether you are assuming any changes and reimbursement for Medicare part B?

所以，即使與第四季的成長動能相比，你們也確實預計2017年的成長將大幅放緩。能否談談這項預期背後的考量因素？特別是，你們是否考慮了Medicare B部分報銷政策的任何變更？

Secondly, what is it you're seeing in terms of penetration particularly in the DME indication that suggests the products reaching maturity now?

其次，您認為在DME適應症領域，產品滲透率有哪些跡象顯示這些產品現在已經成熟？

Thanks Geoff. No snow at all. Let me just address your question generally about our guidance here.

謝謝傑夫。一點雪都沒有。關於你問的我們這裡的指導意見，我只想簡單回答。

I remind you that this will be the last year that we do individual product guidance. You know I'm not a big fan of being in the forecasting business. We are in the drug discovery development and optimization business. And forecasting is always somewhat tenuous.

我提醒各位，今年將是我們最後一年提供單一產品的指導。你們也知道，我不太喜歡做預測工作。我們從事的是藥物發現、開發和優化工作，而預測總是帶有一定的不確定性。

A lot of people have been concerned about how we get to the guidance, and why is the range single digits, which can be rather broad. You have to remember we are a science driven company. And when you look at all of the errors in the estimates of things that can go into it such as market share, anything that could happen in government policy, negotiations, our ability to hold off any growth of Avastin, any market forces that require increase goes to net.

很多人都關心我們是如何得出業績指引的，以及為什麼指引範圍是個位數，這其實相當廣泛。你們要記住，我們是一家以科學為驅動的公司。考慮到所有可能影響業績指引的因素，例如市場份額、政府政策變化、談判進展、我們能否控制阿瓦斯汀（Avastin）的成長，以及任何可能導致業績成長的市場因素，所有誤差都會被納入考量。

When you put all of these puts and takes, if you will, it does become somewhat of a blizzard which obscures the landscape. And it is very difficult to feel comfortable that we can give you precision that you would like when there are too many estimates in there and when you put them all together the precision is just not there.

如果把所有這些投入和撤回都放在一起，就會像暴風雪一樣，把情況搞得一團糟。當估算值太多，加在一起根本達不到預期精度時，我們很難讓人放心，我們能夠提供您所期望的精確度。

So it is the fifth year of this products. We have grown rather substantially. We do think there is growth also to still be had with new indications. Also, obviously growth outside the United States with Bayer. As the year goes on we will see how this all plays out.

今年是該產品上市的第五年，我們取得了相當可觀的成長。我們認為，隨著新適應症的開發，仍有成長空間。此外，拜耳在美國以外的市場也實現了成長。隨著時間的推移，我們將拭​​目以待。

Ronny Gal from Bernstein.

來自伯恩斯坦的羅尼·加爾。

Good morning.

早安.

I want to ask one alternate in case you cannot answer the first one. In case you have the opinion form the court about the preliminary injunction. Can you just us a little color about this? Particularly what was the appellate court's opinion about the likelihood of success of the merits?

如果您無法回答第一個問題，我想問一個備選方案。如果您有法院關於初步禁制令的意見，能否簡單說明一下？特別是上訴法院對案件實體審理成功的可能性有何看法？

If you have not got the opinion yet I would ask you about the Praluent trajectory market share for 2017. Obviously some of your clients will be a bit worried about the potential final outcome. Should we expect you guys to begin to lose a little bit of share against [reposide] in that market?

如果您還沒有形成意見，我想問您關於Praluent在2017年的市佔率預測。顯然，您的一些客戶會對最終結果感到擔憂。我們是否可以預期，你們在該市場（針對回購交易）的份額會開始下降？

Let me deal with the opinion -- the legal opinion -- I think that is what you are asking related to the injunction. By the way it was not a preliminary injunction. It was a permanent injunction, which is what you get at the end after a jury trial. A preliminary injunction is something you might get before a jury trial. Which was not sought in this case.

讓我來談談這份意見——法律意見——我想這正是您詢問的與禁令相關的問題。順便說一下，這不是初步禁令，而是永久禁令，也就是陪審團審判結束後才能獲得的禁令。初步禁制令則是在陪審團審判之前可以獲得的，而本案中並未申請初步禁制令。

We read the opinion which is available online I think you can probably find it linked to our press release. And what the court said -- is as is typical in all cases when they are determining whether to upset, if you will, or put a hold on an injunction that a lower court's issued that they consider four factors.

我們閱讀了這份意見書，我想您應該能在我們的新聞稿中找到它的連結。法院的意見書－正如所有案件的慣例，在決定是否推翻或中止下級法院頒布的禁令時，他們會考慮四個因素。

These factors, the first factor relates to the question of whether you've made a strong showing of a likeliness to win on the underlying appeal. And the second factor has to do with whether or not you will suffer irreparable harm if you do not get this stay during the appeal. And the third factor has to do with how this affects the other party. The fourth factor has to do with how it affects the public.

在這些因素中，第一個因素與你是否已充分證明自己有勝訴的可能性有關。第二個因素與如果你在上訴期間未能獲得暫緩執行令是否會遭受無法彌補的損害有關。第三個因素與此事對對方當事人的影響有關。第四個因素與此事對公眾的影響有關。

From the way that we look at the actual opinion, the court said that the first two of the factors are the most critical. That is whether Regeneron Sanofi have made a strong showing of a likelihood of success from [Amertin], and whether or not we would be irreparably harmed. They said based on the submissions in the papers that they felt that we met that standard, and we were entitled to an injunction to be stayed.

從我們對判決書的解讀來看，法院認為前兩個因素最為關鍵。這兩個因素分別是：Regeneron Sanofi 是否已充分證明其 [Amertin] 藥物有成功的可能性，以及我們是否會遭受無法彌補的損害。法院根據提交的文件認為我們符合這些標準，因此我們有權獲得暫緩執行的禁令。

That is all we know at this point. Now we are moving forward on a somewhat accelerated basis. Our opening brief on the underlying appeal that the judges were talking about when they said whether we made a strong showing of our winning on the success. That is what they are talking about. We're now going to try to go win on the success on the merits.

目前我們掌握的資訊就這麼多。現在，我們正以相對加快的速度推進工作。我們針對上訴的初步陳述，也就是法官所說的，我們是否充分證明了我們在勝訴方面能夠勝訴。他們指的是這一點。現在，我們將努力爭取在案件實質上取得勝訴。

I hope that answers your question.

希望我的回答能解答你的疑問。

Mark Schoenebaum from Evercore

來自 Evercore 的 Mark Schoenebaum

Hi guys thanks a lot for taking my question. Thanks to Michael, [Manisha], and Len for all your help and I was out helping out the team. I really appreciate it, and Len it is great to hear your voice.

大家好，非常感謝你們回答我的問題。感謝Michael、Manisha和Len的幫助，我當時正在幫團隊的忙。我真的很感激，Len，很高興聽到你的聲音。

I thought I would ask a big picture question, and hopefully I can get Len fired up here. President Trump -- it was his press secretary I think a couple days ago -- Len mentioned that he was clearly in favor of the government directly negotiating drug prices with drug manufacturers.

我想問一個比較宏觀的問題，希望能引起倫的共鳴。倫提到，幾天前，川普總統——我記得是他的新聞秘書——明確表示支持政府直接與製藥商談判藥品價格。

I would love to hear your thoughts on this. Do you believe it, what does it mean for the sector if it were implemented, and what kind of impact would it have on drug prices if it were implemented? And more broadly what do you actually think is going to happen with all of this drug pricing stuff? Thanks a lot Len.

我很想聽聽你的看法。你相信這個方案嗎？如果實施，對整個產業意味著什麼？會對藥品價格產生怎樣的影響？更廣泛地說，你認為藥品定價問題最終會如何發展？非常感謝，Len。

You're welcome Mark. Nice to hear your voice as well.

不客氣，馬克。很高興聽到你的聲音。

Look, I don't have a particularly unique pipeline into what the President is thinking here. We take him at his word for what he said that he thinks that the US is paying too much, and is not negotiating. I think as he gets deeper into the policies I think you will find that in fact we do negotiate prices for Medicare drugs. We just do it with individual Medicare carriers rather than one negotiator.

你看，我並沒有什麼特別的管道可以了解總統的想法。我們姑且相信他所說的，他認為美國支付的費用太高，而且不打算進行談判。我認為，隨著他對政策的深入研究，你會發現，實際上我們確實在就聯邦醫療保險藥品的價格進行談判。只不過我們是分別與各聯邦醫療保險承保機構進行談判，而不是由一個談判代表負責。

I think my own perspective on this is that what is going to happen here is a little bit more of a nuanced dialogue that says that the public is going to recognize -- and I think the President recognizes -- that this is a very, very hard business. Innovating and discovering new drugs that can really change people's lives. Either how long they live or the what the quality of their life is, is something that is extremely hard to do.

我認為，接下來會發生的是一場更加細緻入微的對話，公眾將會認識到——而且我認為總統也認識到——這是一項非常非常艱鉅的工作。創新和發現能夠真正改變人們生活的新藥，無論是延長壽命還是提高生活質量，都是極其困難的。

On the other hand it doesn't do us any good to do all of that if we can't get these drugs to people who can actually afford them. Where I actually think that there will be some consensus in Congress. Which this is going to take Congressional action I believe. I think there will be some consensus in trying to deal with how much of the payments individuals are making for drugs.

另一方面，如果我們無法將這些藥物送到真正負擔得起的人手中，那麼我們所做的一切都毫無意義。我認為國會最終會達成一些共識。我相信這需要國會採取行動。我認為在如何解決個人為藥物支付的費用問題上，國會將達成一些共識。

The co-pays or coinsurance's are really what our most problematic for people. I think people are beginning to recognize that the skin in the game that the government wanted for a lot of this has gone a little too far making it hard for people to literally get the drugs. I think some relief there will be forthcoming.

對人們來說，自付額或共同保險才是真正的問題。我認為人們開始意識到，政府在許多方面都要求民眾承擔過多的責任，這導致人們很難真正獲得所需的藥物。我相信這方面會有一些緩解措施出台。

But at the end of the day the attention probably will be -- this just my guess is -- on somehow setting standards that breakthrough drugs ought to be rewarded, and price increases that are unrelated or uncoupled from innovation, that will be pushed back on. The end of the day society is going to have to figure out how to protect incentives for innovation.

但歸根結底，人們的關注點可能——這只是我的猜測——在於如何制定標準，確保突破性藥物能夠得到獎勵，並遏制與創新無關或脫鉤的價格上漲。最終，社會必須找到保護創新激勵機制的方法。

No matter what we've been coming back now that (inaudible). I think Regeneron is extremely well-positioned because I think the winners and losers in our space will be those that are really viewed as our true innovators. I think If you come up with a product like Dupixent -- which hopefully will be approved toward the end of this quarter -- where you can change people's lives, that is always going to get value for you.

不管怎樣，我們現在一直在回歸正軌（聽不清楚）。我認為Regeneron的處境非常有利，因為我認為我們這個領域的贏家和輸家將是由那些真正被視為創新者的公司來決定的。我認為，如果你能研發出像Dupixent這樣的產品——希望它能在本季末獲得批准——能夠改變人們的生活，那麼它就一定會為你帶來價值。

So anyway I will just stop there and take the next question.

那我就先說到這裡，回答下一個問題吧。

Ying Huang from Bank of America Merrill Lynch

來自美國銀行美林證券的黃穎

Hi good morning, thank you for taking my question.

您好，早安，感謝您回答我的問題。

I have a question on EYLEA. Should we assume that your market share in 2017 in AMD and DME will be relatively stable? That is how you come to the single digit guidance.

我有一個關於愛立信的問題。我們是否可以假設貴公司2017年在AMD和DME市場的佔有率將相對穩定？貴公司給出個位數成長預期就是基於這個假設。

And unrelated to that Novartis has a phase 3 for RTH 258 that is comparing a Q3 month regimen to the Q2 month for EYLEA. I'm wondering if you guys have any thought about that? Thank you.

另外，諾華公司正在進行RTH 258的3期臨床試驗，該試驗比較了每3個月給藥一次的方案與EYLEA每2個月給藥一次的方案。不知道各位對此有何看法？謝謝。

I'm not going to get into the granular basis of how we came up with our assumptions Ying. Because as I said you start to add them up and you wind up with lots of errors. So it's not like one thing drove it versus another. So we will keep you posted on a retrospective basis how our market share is doing, but predicting that it's very, very difficult

穎，我不想詳細解釋我們是如何得出這些假設的。因為正如我所說，一旦把所有假設加起來，就會發現很多錯誤。所以，這並不是某個因素主導了我們的決策。我們會定期向你報告我們的市佔率狀況，但要預測未來真的非常非常困難。

George can address the Novartis trial.

喬治可以談談諾華公司的試驗。

We want to remind you that their study is really just intended to show that some percentage of their patients can get by with every three months dosing. And we have already shown data that shows that a substantial number of our patients can also get by with three months dosing.

我們想提醒您，他們的研究實際上只是為了表明，他們的一部分患者可以每三個月接受一次治療。而我們已經提供的數據表明，我們相當一部分患者也可以每三個月接受一次治療。

I think that neither they nor I are advocating three months dosing for every patient. It's just that they're trying to produce data akin to ours, which actually shows that a substantial number of patients can indeed get by with every three months dosing.

我認為他們和我都沒有提倡對所有患者都採取三個月一次的給藥方案。他們只是試圖得出與我們類似的數據，這些數據實際上表明，相當一部分患者確實可以每三個月給藥一次。

I will just say that look this is a hard business. And you load up the eye with a lot of drugs, and which is what they're doing. They will have to show that they do not get inflammation, and they'll have to show that you do not get hypertension systemically which is seen in some of the earlier trials, and you just don't know.

我只想說，這可不是件容易的事。他們現在正在往眼睛裡注射大量藥物。他們必須證明不會引起炎症，也必須證明不會引起全身性高血壓（早期的一些試驗中觀察到了這種情況），但結果如何，誰也說不準。

So we will have to wait and see and we will look at their data. But as George said, I'm not sure that the way that they have set up the trials will accomplish anything more than we already have data for. So we will see.

所以，我們只能拭目以待，看看他們的數據。但正如喬治所說，我不確定他們設計的試驗方式能否比我們現有的數據帶來更多益處。所以，我們拭目以待。

Len brings up an important point. They're trying to do it by putting in many, many more molecules of their agent as compared to EYLEA. To get a rather similar efficacy bar, and with that as Len pointed out comes additional risks they are going to have to show that they are not actually causing.

Len提出了一個重要的觀點。他們試圖透過添加比EYLEA多得多的藥物分子來實現這一點，以達到相近的療效。但正如Len所指出的，這樣做會帶來額外的風險，他們必須證明這些風險並非實際存在。

Chris Raymond from Raymond James.

來自 Raymond James 的 Chris Raymond。

Thank you for taking the question.

感謝您回答這個問題。

So the question for the Sarilumab. Assuming you guys get a timely US approval here. If some of our survey were to have shown real traction for a [chemra], especially in its subQ format with what looks like real impact on Embryl and Humira. At least from my view Sarilumab has had pretty significant differentiation versus (inaudible), you have got this positive head-to-head trial versus Humira. Its a more convenient administration et cetera.

所以，關於Sarilumab的問題。假設你們能及時獲得美國批准。如果我們的調查顯示，這種化學製劑（尤其是皮下注射劑型）確實有效，並且對Embryl和Humira產生了實際影響，那麼至少在我看來，Sarilumab與（聽不清）相比具有相當顯著的差異化優勢，而且你們還有一項與Humira的正面頭對頭試驗結果。它的給藥方式也比較方便等等。

So Len even as you mentioned on this call. You've been a pretty outspoken critic of pharma pricing. The TNF market has been a more glaring example of aggressive pricing practice. And I know Len you do not want to talk about specific pricing strategies.

萊恩，正如你在這通電話中提到的，你一直以來都對藥品定價持批評態度。 TNF市場就是一個定價激進的典型例子。我知道萊恩，你不想談論具體的定價策略。

But you guys really struck a great note with the pricing decision on EYLEA. Would you say that the inflammatory Biologics market allows a similar setup here for you to really make a statement? Or is that market different from the one that EYLEA launched into?

但你們在EYLEA的定價策略上確實做得非常好。您認為發炎性生物製劑市場是否也允許你們採用類似的策略來發出自己的聲音？或者說，這個市場與EYLEA上市時所處的市場有所不同？

Chris in a word, yes. We think that the constant price increases, and the magnitude of them, are a reflection of several things. One somewhat tone deafness on the people taking these huge increases. And somewhat of complexities of the system about how all of these rebates work.

克里斯，一言以蔽之，是的。我們認為，物價持續上漲，而且漲幅如此之大，反映了幾個問題。首先，人們對這些巨額漲價的感受有些麻木。其次，所有這些返利機制的運作方式也相當複雜。

I think some of this is being unwound. So we do have sort of a three-part strategy. If we get Capzara to market. Which I expect we will. One is to provide it as a reasonable alternative to anti-TNF therapy. Either in first-line or after failures.

我認為其中一些問題正在解決。所以我們有一個三步驟的策略。如果我們能成功將Capzara推向市場（我預計會成功），第一步是將其作為抗TNF療法的合理替代方案，無論是作為一線治療還是在抗TNF療法失敗後使用。

The second is to try and position it, if we can, as the preferred IL-6 agent based on the profile of the product. We'll have to see how doctors respond to that. And by the way, there is this growing market for monotherapy. Which I think as you mentioned we do have attractive data in.

第二點是，如果可能的話，我們會嘗試根據產品的特性，將其定位為首選的IL-6治療藥物。我們需要觀察醫生對此的反應。順便一提，單藥治療市場正在不斷成長。正如您所提到的，我們在這方面確實擁有一些很有吸引力的數據。

So monotherapy, that is without methotrexate which is not the most well-liked to drug to be frank, is a growing part of the market. And the third part of our strategy is the one that you just referred to. Which is that there is an opportunity to come up with more responsible pricing. That is all that I should say at this point.

所以，單藥療法，也就是不使用甲胺蝶呤（坦白說，甲氨蝶呤並不是最受歡迎的藥物），正在成為市場份額不斷增長的一部分。我們策略的第三部分就是您剛才提到的，那就是有機會制定更合理的定價策略。目前我只想說這些。

Robyn Karnauskas from Citigroup

來自花旗集團的 Robyn Karnauskas

Hi guys thank you for taking my questions.

大家好，感謝你們回答我的問題。

I just want to ask another pricing question. Can you talk a little bit about if you seen any pricing (inaudible) in the US and Europe. You did mention on pricing for, I can never pronounce it, (inaudible), you talked about (inaudible) will be positioned positively.

我只想再問一個定價方面的問題。您能否談談您在美國和歐洲是否看到任何定價（聽不清楚）的情況？您之前提到過，關於某個（聽不清楚）的定價，我總是念不出來，您還說過（聽不清楚）的定位會是正面的。

Maybe talk about how you think about the lesson from pricing PCSK9, and where you might be getting you confidence to positioning on the formulary for [TB]. Thank you.

或許可以談談您如何看待PCSK9定價的經驗教訓，以及您如何獲得對[TB]藥物納入藥品目錄定位的信心。謝謝。

Yes, good question Robyn, thanks.

是的，羅賓，問得好，謝謝。

PCSK9 story will be a case study. There a lot of views on this and the complexities in the context that they were launched following the Hep-C struggles that payers and manufactures had. Makes that somewhat of a unique story. Combined with the fact that you had a market of pennies a day fabulous statins, which really could serve a lot of the market, obviously.

PCSK9的故事將作為一個案例研究。關於PCSK9有很多不同的看法，而且由於它是在丙肝治療領域，支付方和製藥商都面臨困境之後推出的，其背景也相當複雜。這使得PCSK9的故事具有一定的特殊性。此外，當時市面上還有價格低廉、效果顯著的他汀類藥物，顯然，這些藥物能夠滿足很大一部分市場需求。

In our drug Dupixent this is a whole different story. First of all we have outcomes data now. The outcomes data are the endpoints. People's skin and their itch, and their itch is really a big deal, are getting dramatically better. And I think that -- so when you are starting with that it is very important.

就我們的藥物Dupixent而言，情況完全不同。首先，我們現在有了療效數據。療效數據指的是終點指標。患者的皮膚狀況和搔癢症狀（搔癢確實是一個非常嚴重的問題）都得到了顯著改善。我認為——所以，從這一點入手非常重要。

You are also going into a field which the FDA has said it's a breakthrough. We think it's a breakthrough. I think my discussions with payers, their people think it's a breakthrough. Most importantly the patients and the doctors believe it is a breakthrough.

您即將進入的領域也被FDA譽為突破性進展。我們認為這是一項突破。我認為我與支付方及其工作人員的討論也表明這是一項突破。最重要的是，患者和醫生都相信這是一項突破。

So that is a whole different kettle of fish than when you are dealing with the drug -- for example a cholesterol-lowering drug where people are not even sure that they want to have their cholesterol lowered. Or if it was any good to have their cholesterol lowered. We believe that it was of course, but there was this pushback.

所以，這和處理藥物的情況完全不同——例如，對於降膽固醇藥物，人們甚至不確定自己是否想要降低膽固醇，或者降低膽固醇是否有好處。我們當然認為有好處，但當時確實存在一些阻力。

Here with this drug people want this drug, people need this drug, and I think that the data are remarkably consistent across all of our trials. It really is a breakthrough. So we have had very productive conversations meeting with payers, who I think have been receptive to trying to not make is always so adversarial.

人們想要這種藥，人們需要這種藥，而且我認為我們所有試驗的數據都非常一致。這確實是一項突破。因此，我們與支付方進行了非常有成效的對話，我認為他們也願意盡量避免總是充滿對抗性。

We have a role, they have a role, and we can spend a lot of time pointing fingers at each other, like a lot of people do. Pharma's running around saying the middleman is taking too much of it. The middleman is saying that the prices are too high. The patients are wondering what the hell is really going on. Or we can try to work together and come up with a breakthrough product that has responsible pricing, and good solid formulary access without significant barriers to the right patients getting the drug.

我們各自都有責任，他們也有責任，我們可以像許多人一樣，花很多時間互相指責。製藥公司到處抱怨中間商賺太多，中間商則抱怨價格太高。患者們則一頭霧水，不知這到底是怎麼回事。或者，我們可以嘗試合作，研發出突破性產品，定價合理，並能有效納入健保目錄，確保真正需要用藥的患者都能獲得藥物。

I am an optimist and I base that optimism not just based on my genetic makeup, but on the fact that I've actually had conversations with the most senior leaders of the most important payers. And I have felt that we have gotten a very good reception to our approach. I am really looking forward to telling you the details when we launch, and to getting this product to patients.

我是一個樂觀主義者，我的樂觀並非僅僅源於我的基因，而是因為我曾與最重要的支付方的高層領導進行過深入的交流。我感覺到我們的方案得到了很好的迴響。我非常期待在產品上市時與大家分享更多細節，並儘快將這款產品帶給患者。

Adnan Butt from RBC Capital Markets.

來自加拿大皇家銀行資本市場的阿德南·巴特。

Hi thanks.

謝謝。

Maybe for George. Based on either a phase 1 or biology. You mentioned the bar is high versus EYLEA, but is the bar different than what you would have expected for PDGF?

或許對喬治來說是這樣。這要基於一期臨床試驗或生物學研究。你提到與EYLEA相比，PDGF的門檻很高，但這個門檻與你預期的PDGF的門檻有何不同？

I think the preclinical data was just very weak for the PDGF class. We have been working on that for 20 years, and largely went into that program as a defense of strategy. Just in case some how the anomalous early clinical data were proven to be true.

我認為PDGF類藥物的臨床前數據確實非常薄弱。我們已經在這個領域研究了20年，當初進入這個計畫很大程度上是為了應對策略上的挑戰，以防萬一那些異常的早期臨床數據最終被證實是真的。

ANG2 the data, the preclinical data is much stronger. But as you said EYLEA poses such a high bar for efficacy. That it is a challenge for anything to improve it. Especially EYLEA does such a good job on things like retinal edema. Which is one of the major causes of reversible vision loss.

ANG2 的數據，尤其是臨床前數據，要強得多。但正如您所說，EYLEA 的療效標準​​非常高，任何藥物想要超越它都是一項挑戰。尤其是在視網膜水腫等方面，EYLEA 的表現非常出色，而視網膜水腫正是導致可逆性視力喪失的主要原因之一。

So we're anxious to see, testing the hypothesis and patients, we think it is worth going forward and testing. We hope for patients sake that it is going to make an improvement, but like anything else, it is a high bar and it is going to be hard to actually be the.

所以我們很想看看，透過對患者進行試驗，驗證這個假設，我們認為值得繼續推進試驗。我們希望為了病人的利益，它能有所改善，但就像其他事情一樣，這需要很高的標準，真正達到目標會很困難。

Yatin Suneja from SunTrust.

來自 SunTrust 的 Yatin Suneja。

Good morning guys. Thank you for taking my question.

各位早安。感謝你們回答我的問題。

My question is on Praluent. Could you guys comment on how the ODYSSEY OUTCOME trial might differentiate Praluent versus the Repatha? And then George you mentioned you're expecting increased uptick after positive data in appropriate patients. Could you maybe expand on that, how do you define that appropriate patient population? Thank you.

我的問題是關於Praluent的。你們能否談談ODYSSEY OUTCOME試驗的結果如何區分Praluent和Repatha？另外，George，你提到在合適的患者群體中獲得積極數據後，你預計銷量會上升。你能否詳細說明一下，你們如何定義「合適的患者群體」？謝謝。

Right. It is a little bit early to answer the question on how we are going to differentiate. We know that the trials are slightly designed differently in different patient populations. But we have not seen any data yet whatsoever.

沒錯。現在回答如何區分還為時過早。我們知道，針對不同患者群體，試驗設計略有不同。但我們目前還沒有看到任何數據。

All we have heard is top line data. So we have to wait until we actually get our data, and analyze carefully the data that is being presented. George you can comment.

我們目前聽到的都是一些概括性的數據。所以我們必須等到拿到實際數據後，才能仔細分析這些數據。喬治，你可以發表一下看法。

Just remind you are that our patient population was a higher risk population post acute coronary syndrome type populations. So you might expect that these patients might have both a higher risk, which is one reason why our study had less study numbers of overall patients than the Repatha the study. But also that you might have a different degree of benefit in these patients, and that it might be represented in different components that comprised of various events of interests.

需要提醒您的是，我們的患者群體屬於高風險族群，即急性冠狀動脈症候群後族群。因此，這些患者的風險可能更高（這也是我們研究的患者總數少於Repatha研究的原因之一），但同時也可能從治療中獲益程度不同，而這種獲益可能體現在構成各種相關事件的不同方面。

In terms of appropriate patients -- I think that was actually Bob that it mentioned it-- but what he was saying is that we want people to have their maximally tolerated statins before they go on to choose Praluent to further lower their LDL, assuming that they have the appropriate atheros cardiovascular disease.

關於合適的患者——我想實際上是鮑勃提到了這一點——他的意思是，我們希望患者在選擇 Praluent 來進一步降低 LDL 之前，先服用最大耐受劑量的他汀類藥物，前提是他們患有合適的動脈粥樣硬化性心血管疾病。

In terms of getting more patients through the system, I think this will be driven both by doctors -- there are obviously some doctors who have been waiting for outcomes, and only using it in their most severe patients with severe hypercholesterolemia. But now, I think that might change. So you might get more drive and more prescriptions coming through.

就如何讓更多患者接受治療而言，我認為這將由醫生和臨床醫生共同推動——顯然，有些醫生一直在等待療效，只對病情最嚴重的重度高膽固醇血症患者使用這種藥物。但現在，我認為這種情況可能會改變。因此，我們可能會看到更多醫生積極推動治療，並開出更多處方。

I also believe that with outcomes data the payers are not insensitive to the change in the science. And they will evaluate this, and think about the various barriers that are in place. I believe they may lessen some of those barriers to make it somewhat easier to get these prescriptions to go through.

我也相信，有了療效數據，支付方並非對科學進展漠不關心。他們會評估這些數據，並考慮目前存在的各種障礙。我相信他們可能會減少其中一些障礙，使這些處方更容易獲得批准。

There is one important thing though, whenever we talk about differentiation from Repatha we need to keep in mind that we are differentiated. This is the only molecule that has a low dose option.

不過，有一點很重要，每當我們談到與瑞百安（Repatha）的差異時，都必須記住，我們確實是不同的。這是唯一一種有低劑量方案的分子。

There are a large number of patients receiving that low dose option, and a large number of physicians who prefer to start with that dose. That is how we conduct at the ODYSSEY OUTCOME study.

有很多患者接受了低劑量治療方案，也有很多醫生傾向於從這個劑量開始。我們在 ODYSSEY OUTCOME 研究中就是這樣做的。

Yep. Thank you. Okay, Michael next question.

是的，謝謝。好的，邁克爾，下一個問題。

Alyssa Young from Credit Suisse

瑞士信貸的艾莉莎楊

Hi guys. Thank you for taking my question.

大家好。感謝你們回答我的問題。

It seems like the FDA has been tougher on manufacturing and stuff. So I know that you have sort of address some things with (inaudible). But maybe can you talk about how the breakthrough designation has helped with the Dupixent? And what are the remaining steps and how confident you feel about being on time for this approval?

FDA似乎對生產環節等方面更加嚴格了。我知道你們已經就一些問題（聽不清楚）進行了處理。但能否談談突破性療法認定對Dupixent的幫助？接下來的步驟是什麼？您對按時獲得批准有多大信心？

Yes, I think the FDA has been and should be tough about manufacturing. You know, we rely on our system. Both self regulated. Responsible manufacturers regulating their production and quality. As well as third-party regulators, the FDA to ensure the quality of our drugs.

是的，我認為FDA過去一直對藥品生產嚴格監管，現在也應該如此。你知道，我們依賴現有的監管體系。此體系既包括自我監管，即負責任的生產商監管其生產和品質；也包括第三方監管機構，例如FDA，以確保我們藥品的品質。

We have no problem with that at all. And I think that Sanofi doesn't either and they have worked hard now to improve and get that plan in an acceptable format.

我們對此完全沒有異議。我認為賽諾菲也沒有異議，他們現在也一直在努力改進，使該計劃成為一個可以接受的形式。

We still have to go through the routine. Pre approval inspections, routine in the sense -- It's not a routine inspection, it's a routine in the sense that you have to have it before a drug is approved. But we have been through those before. As they have. We are optimistic and we have worked very hard to get ready for that, and expect that we should be able to get through that.

我們仍然需要走完所有流程。審批前檢查，這裡的「流程」並非泛泛之談，而是指藥物獲批前必須經過的檢查。但我們之前已經經歷過這些，他們也是。我們對此充滿信心，並為此做了大量準備工作，相信能夠順利通過。

If we do we would expect and approval by the end of the year. I mean the end of the quarter. Sorry.

如果可以的話，我們預計年底前會獲得批准。我是說季度末。抱歉。

In terms of the breakthrough status. Actually that has been very, very helpful. I think it is a terrific program that Congress devised. Because it gets the focus of the people, it gets the staffing on the project to move things along, it gets you more access to get your questions answered, et cetera et cetera.

就突破性進展而言，實際上它非常非常有幫助。我認為這是國會制定的一項非常棒的計劃。因為它能引起民眾的關注，能為專案配備人員以推進進展，能讓你更容易獲得問題的解答等等。

So I do think that its a good program. My perspective on it is that they do not give it out so easily. They have high standards, and when you get it they do work well with you. So no gripes from me.

所以我認為這是一個不錯的項目。我的看法是，他們不會輕易錄取。他們的標準很高，但一旦你被錄取，他們會很認真地幫助你。所以我沒什麼好抱怨的。

I am not one of those people who when things don't go well I just blame the FDA. It's just the opposite. I want a tough FDA, because I want a high bar. I want a balanced and fair playing field, but I want a high bar so that we are just not in the if you will -- I said the other day in the infomercial business, and anything you can say is fine and doesn't matter whether the product actually works or not.

我不是那種遇到問題就怪罪FDA的人。恰恰相反。我希望FDA嚴格執法，因為我想要高標準。我想要一個公平公正的競爭環境，但我更希望標準高一些，這樣我們就不會陷入——就像我前幾天在電視購物廣告裡說的那樣——什麼都行，產品到底有沒有效根本不重要。

We have time for one more question. For those of you who do not get to ask a question today I apologize. We are in the office. So please give us a call, and we will try to get you on in the next earnings call. So this will be the last question.

我們還有一個問題要問。今天沒能提問的各位，我深感抱歉。我們現在都在辦公室。所以請給我們打電話，我們會盡量在下次財報電話會議上安排您參加。這將是最後一個問題。

Cory Kasimov from JPMorgan.

摩根大通的科里·卡西莫夫。

Hi good morning guys. Thank you for taking my question and squeezing me in.

各位早安。感謝你們抽空回答我的問題。

Relatively speaking how do you view the market opportunity for EYLEA in non-proliferative diabetic retinopathy compared to the products currently approved indications? Assuming of course you have positive phase 3 data for that patient population?

相對而言，您如何看待EYLEA在非增殖性糖尿病視網膜病變領域的市場機會，與目前已獲批准適應症的產品相比？當然，前提是您已獲得針對該患者群體的積極的3期臨床試驗數據。

Thanks.

謝謝。

Once again, I'm glad you asked the question on the way you did. On a relative basis the number of patients is substantially higher who have proliferative diabetic retinopathy as compared to those who have proliferative diabetic retinopathy with diabetic macular edema. So you open up a much larger group of patients who potentially could benefit from the drug.

再次感謝您以這種方式提出問題。從相對數量來看，單純患有增殖性糖尿病視網膜病變的患者人數遠高於同時患有增殖性糖尿病視網膜病變和糖尿病黃斑水腫的患者。因此，您提出的藥物可能惠及更多患者。

Of course this is sort of almost treating people who have eye disease, lots of eye disease, but it has not affected their vision yet. So you have to convince them that to get an injection in the eye to protect their vision. I think that is somewhat of an impediment, but if you have strong data the numbers there are much, much larger. Anyway, so I think it is a big opportunity on a relative basis.

當然，這有點像是在治療患有眼疾（很多眼疾）但視力尚未受損的患者。所以你必須說服他們接受眼內注射來保護視力。我認為這在某種程度上是個障礙，但如果你有可靠的數據，那麼潛在的治療對象就非常多。總之，我認為從相對角度來看，這是一個巨大的機會。

Let me just close by saying that for us, we get it. We know how important EYLEA is. So we are going to defend and try to extend that. We also get how important it is to make our late stage pipeline a big commercial success. We have worked very, very hard to get ready for what we think could be a game changing -- and people like to use game changing, breakthrough, all that stuff -- but the truth of the matter is all those kinds of products do not come along all that often.

最後我想說的是，我們明白這一點。我們知道EYLEA有多重要。所以我們會捍衛它，並努力拓展它。我們也明白，確保我們後期研發管線取得巨大的商業成功至關重要。我們為此付出了巨大的努力，為我們認為可能具有顛覆性意義的產品做好準備——人們喜歡用「顛覆性」、「突破性」之類的詞——但事實是，這類產品並不常見。

Where George and his team are able to give us a weapon, to address, really almost put your finger on the control system for allergic diseases. And do that in a way where you do not have the immune system dysfunction that you do when you do that for type I immunologic disorders. Such as the anti-TNF. Which do great things. If you think about it, when you control the anti-TNF part of the immune system you are able to come up with drugs that treat rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosis spondylitis, Crohn's disease. That is pretty amazing, but on the other hand it came with some risk.

喬治和他的團隊能夠為我們提供一種武器，真正有效地控制過敏性疾病，幾乎可以說是精準地找到了癥結所在。而且，這種方法不會像治療I型免疫疾病（例如抗TNF療法）那樣導致免疫系統功能失調。抗TNF療法效果顯著。想想看，控制免疫系統中的抗TNF成分，就能研發出治療類風濕性關節炎、乾癬、乾癬性關節炎、僵直性脊椎炎和克隆氏症的藥物。這非常了不起，但另一方面，它也存在著一定的風險。

On the other side of the immune system, if you can control that the way Dupixent seems to be able to do. We might be able to have a drug that can address lots of allergic disorders. Not just the first one. The way that these are regulated, and the way that these are can be promoted are only indication by indication. But there are lots of indications here.

另一方面，如果能像Dupixent一樣控制免疫系統，我們或許就能研發出一種可以治療多種過敏性疾病的藥物，而不僅僅是過敏原。這些機制的調控方式以及促進方式目前尚不完全清楚，但目前已知的適應症很多。

You can think of it as we have a drug for atopic dermatitis. We have a drug for potentially asthma. A drug for potentially for nasal polyps with chronic sinusitis, potentially for food allergies, eosiinophilic esophagitis, and so on. To be able to have that control without having the side effects profile that you get from the other side of the immune system. The anti-TNFs. I think it's quite remarkable.

你可以這樣理解：我們有治療異位性皮膚炎的藥物，有治療氣喘的藥物，有治療慢性鼻竇炎伴隨鼻息肉的藥物，有治療食物過敏、嗜酸性粒細胞性食道炎等等的藥物。能夠在控制這些疾病的同時，避免免疫系統另一側（抗TNF）藥物的副作用，我認為這非常了不起。

We are extremely excited about that, and where the science is taking us there. And how the Company can evolve from what are tremendous opportunities on that side of the equation.

我們對此感到無比興奮，也對科學將我們引向何方感到激動。公司如何利用這方面蘊藏的巨大機會而發展壯大，我們深感欣喜。

We're not giving up, obviously, we think Praluent, obviously we're very pleased when that came out last evening. And we will fight very hard to get our appeal successfully, and to make that an important product as well. And our pipeline with all the things in it in a tough pricing environment I think Regeneron is really the place to be because you get innovation. Innovation is something that will always generate value. Price increases are nice, but if you cannot get them you better be able to innovate. That is our sweet spot.

我們當然不會放棄，我們對Praluent昨晚的上市感到非常高興。我們會全力以赴爭取上訴成功，並努力使它成為一款重要的產品。在當前嚴峻的定價環境下，憑藉我們豐富的研發管線，我認為Regeneron仍然是最佳選擇，因為在這裡可以獲得創新。創新永遠是創造價值的泉源。價格上漲固然可喜，但如果無法實現價格上漲，就必須不斷創新。這正是我們的優勢。

So, maybe, Michael I will turn it back over to you.

所以，邁克爾，或許我會把它交還給你。

That concludes our call for today. We appreciate everyone calling in. Again, a couple of people have emailed me. We will call you back. If you want to hear from us give us an email or drop us a line. We are in the office.

今天的電話會議到此結束。感謝各位的來電。再次提醒，有幾位朋友給我寄了電子郵件，我們會盡快回覆。如果您想與我們聯繫，請給我們發送電子郵件或留言。我們現在在辦公室。

Operator, that concludes our call.

接線員，通話到此結束。

Thank ladies and gentlemen. This concludes today's conference. Thank you for participating.

女士們、先生們，謝謝。今天的會議到此結束。感謝各位的參與。