雷傑納榮製藥 (REGN) 2016 Q3 法說會逐字稿

Welcome to the Regeneron Pharmaceuticals Q3 2016 earnings conference call. My name is Jason and I'll be your Operator.

歡迎參加 Regeneron Pharmaceuticals 2016 年第三季財報電話會議。我叫傑森，我將是你的接線生。

(Operator Instructions)

（操作說明）

Please note this conference is being recorded. I will now turn the call over to Dr. Michael Aberman. Dr. Aberman, you may begin.

請注意，本次會議正在錄影。現在我將把電話交給邁克爾·阿伯曼博士。阿伯曼博士，你可以開始了。

Thank you very much and good morning, everyone. Welcome to the Regeneron Pharmaceuticals third quarter 2016 conference call. An archive of this webcast will be available on our website under events and presentations for 30 days.

非常感謝，大家早安。歡迎參加 Regeneron Pharmaceuticals 2016 年第三季財報電話會議。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 of Regeneron Laboratories 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 questions and answers.

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；Regeneron Laboratories 的創始科學家、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 include forward-looking statements about Regeneron. Such statements may include but are not limited to those related to Regeneron and its product and businesses, sales and expense forecasts, financial forecasts, development programs, collaborations, finances, regulatory matters, coverage and reimbursement matters, intellectual property, litigation matters, 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.

我還要提醒各位，本次電話會議中發表的言論包含 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、銷售和費用預測、財務預測、開發計劃、合作、財務、監管事項、承保和報銷事項、智慧財產權、訴訟事項和競爭相關的聲明。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。

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 September 30, 2016 which was filed with the SEC this morning. Regeneron does not undertake any obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise.

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 2016 年 9 月 30 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 rest of 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. Leonard Schleifer.

通話結束後，鮑勃·蘭德里和投資者關係團隊的其他成員將回答進一步的問題。接下來，我將把電話交給我們的總裁兼執行長倫納德‧施萊弗博士。

Thanks, Michael, and a very good morning to everyone who has joined us on the call and webcast today. I'd like to begin by giving you a high level sense of our near-term and longer-term priorities at Regeneron.

謝謝邁克爾，也祝今天所有參加電話會議和網路直播的朋友們早安。首先，我想向大家簡單介紹一下 Regeneron 近期和長期的優先事項。

EYLEA, our flagship anti-VEGF, continues to remain a key financial driver for Regeneron. We are pleased with the continued growth of EYLEA and are committed to maintaining our leadership position in the branded anti-VEGF market by pursuing both additional indications for EYLEA, such as diabetic retinopathy, where we currently have a Phase III study ongoing, and we are also looking at ways in which we can improve upon the high efficacy bar set by EYLEA through combinations with an antibody to ANG-2 where we currently have two Phase II studies ongoing.

EYLEA 是我們的旗艦抗 VEGF 藥物，它仍然是 Regeneron 的主要財務驅動力。我們對 EYLEA 的持續成長感到滿意，並致力於透過以下方式維持我們在品牌抗 VEGF 市場的領先地位：一方面，我們正在尋求 EYLEA 的其他適應症，例如糖尿病視網膜病變（我們目前正在進行一項 III 期研究）；另一方面，我們也在探索如何透過與抗 ANG-2 抗體聯合使用來提高 EYLEA 正在進行兩項的高效性（我們目前正在進行兩項的高效性研究）。

While EYLEA remains very important to our business, we are equally focused on the ongoing launch of PRALUENT, our PCSK9 antibody for lowering LDL cholesterol, as well as advancing our pipeline. For PRALUENT, we believe that if outcomes data are positive, it will drive greater use of this class. As mentioned in our press release, we expect the second interim analysis by the end of this month.

雖然 EYLEA 對我們的業務仍然非常重要，但我們同樣專注於 PRALUENT 的持續上市，PRALUENT 是一種用於降低 LDL 膽固醇的 PCSK9 抗體，同時我們也在推進我們的研發管線。對於 PRALUENT，我們相信，如果結果數據是積極的，這將推動此類藥物的更廣泛使用。正如我們在新聞稿中提到的，我們預計將在本月底發布第二次中期分析報告。

Moving on to sarilumab, our IL-6 receptor antibody for the treatment of rheumatoid arthritis, as you heard last week we received a complete response letter from the FDA. This was due to certain manufacturing deficiencies, not specific to sarilumab, that were observed during a routine inspection of a Sanofi fill and finish plant in France. Sanofi has provided comprehensive responses and is working closely with the FDA to address the deficiencies as expeditiously as possible.

接下來談談 sarilumab，這是一種用於治療類風濕性關節炎的 IL-6 受體抗體。正如您上週聽到的，我們收到了 FDA 的完整回覆函。這是由於在對法國賽諾菲灌裝和包裝工廠進行例行檢查時發現的某些生產缺陷造成的，這些缺陷並非沙利魯單抗特有的。賽諾菲已作出全面回應，並正與FDA密切合作，以盡快解決這些缺陷。

It has only been a week since we received the complete response letter and we are preparing to engage in meaningful discussions with the FDA. So, it is too early for us to comment on the expected timeline for potential sarilumab approval. We do not expect these manufacturing deficiencies will impact sarilumab, or, as it is now known by its brand name, DUPIXENT, where our biological license application, or BLA, is currently under FDA priority review for the treatment of moderate to severe atopic dermatitis in adults. The FDA action date for the BLA is at the end of March.

收到完整的回覆函才一週時間，我們正準備與FDA展開有意義的討論。因此，現在評論 sarilumab 可能獲批的預期時間表還為時過早。我們預計這些生產缺陷不會影響 sarilumab，或現在以其品牌名稱為 DUPIXENT 的產品，我們的生物製品許可申請 (BLA) 目前正在接受 FDA 的優先審查，用於治療成人中度至重度異位性皮膚炎。FDA對該生物製品許可申請的審批日期定在3月底。

DUPIXENT is a very important pipeline product candidate for us and we believe that atopic dermatitis represents an area of high unmet need. As a reminder, we received breakthrough designation this indication. In addition to atopic dermatitis, we are also investigating DUPIXENT in other indications, including asthma, where we recently completed enrollment in our second pivotal study.

DUPIXENT 是我們非常重要的在研產品，我們認為異位性皮膚炎代表著一個尚未充分滿足的醫療需求領域。再次提醒，我們已獲得此適應症的突破性療法認定。除了異位性皮膚炎外，我們還在研究 DUPIXENT 在其他適應症中的應用，包括氣喘，我們最近完成了第二項關鍵性研究的患者招募。

In the mid term, we are looking forward to important clinical progress from several of our Phase II and three programs, which span a variety of therapeutic areas such as allergic diseases, pain, viral diseases, ophthalmology, oncology, cardiometabolic disease, inflammatory and rare diseases. These programs have the potential to drive the next wave of growth for Regeneron. You will hear more about the key clinical developments from some of these programs from George.

中期來看，我們期待幾個 II 期和 III 期計畫取得重要的臨床進展，這些計畫涵蓋了過敏性疾病、疼痛、病毒性疾病、眼科、腫瘤科、心血管代謝疾病、發炎和罕見疾病等多種治療領域。這些項目有可能推動 Regeneron 的下一波成長浪潮。喬治會向你詳細介紹其中一些計畫的關鍵臨床進展。

At Regeneron we've always been committed to long-term science and innovation. In fact, today's marketed products, as well as the 16 product candidates in clinical development, were all homegrown in our internal R&D engine. We will continue to invest in science and technology that can provide sustainable innovation and growth well into the future.

Regeneron始終致力於長期科學研究和創新。事實上，目前市售的產品以及 16 個正在進行臨床開發的候選產品，都是我們內部研發團隊自主研發的。我們將繼續投資科學技術，以實現永續的創新和成長，並確保未來的永續發展。

This unique long-term focus on science is at the heart of why we have been able to attract top talent, which is key to our continuing success. To that end, last week, we were thrilled to be named by Science Magazine as the number one company in the biotech or pharmaceutical industry to work for, a recognition we've received for four of the last six years.

這種對科學的長期獨特關注是我們能夠吸引頂尖人才的核心原因，也是我們持續成功的關鍵。為此，上週我們非常高興地被《科學》雜誌評為生物技術或製藥行業最佳雇主，這是我們在過去六年中有四年獲得的認可。

We know that our industry has faced many important questions regarding pricing of drugs. This is not the forum to discuss the complex issue of drug pricing but I think it is important to note that Regeneron is in a unique position.

我們知道，我們行業在藥品定價方面面臨許多重要問題。這裡不是討論藥品定價這一複雜問題的合適場所，但我認為有必要指出，Regeneron 處於一個獨特的地位。

As a company founded on science and committed to the research and development of important new products, we are well positioned to succeed even in a difficult and constrained pricing environment. In fact, we have never raised prices on any of our drugs, choosing instead to grow through the optimization of currently marketed products by pursuing new indications, as well as the introduction of new medicines. Our future potential growth will be driven by this strategy.

作為一家以科學為基礎，致力於重要新產品研發的公司，即使在艱難且受限的定價環境下，我們也具備成功的良好基礎。事實上，我們從未提高過任何藥品的價格，而是選擇透過優化現有上市產品、探索新的適應症以及推出新藥來成長。這項策略將推動我們未來的潛在成長。

With that, let me turn the call over to George.

那麼，我把電話交給喬治吧。

Thank you, Len, and a very good morning to everyone who has joined us today. I'd like to begin with DUPIXENT, our IL-413 blocker, which we believe is one of the most exciting late-stage drug candidates in the industry. We are investigating DUPIXENT in a wide variety of allergic diseases, the most advanced of which is uncontrolled moderate to severe atopic dermatitis.

謝謝Len，也祝今天到場的各位早安。我想先介紹一下我們的 IL-413 阻斷劑 DUPIXENT，我們認為它是業內最令人興奮的後期候選藥物之一。我們正在研究 DUPIXENT 在各種過敏性疾病中的療效，其中最嚴重的是無法控制的中度至重度異位性皮膚炎。

Just last month, we had the opportunity to present detailed results from SOLO 1 and SOLO 2, which were two identical Phase III studies that investigated DUPIXENT in the monotherapy setting at the annual EADV conference. These data were also concurrently published in the New England Journal of Medicine.

就在上個月，我們有機會在 EADV 年度大會上展示 SOLO 1 和 SOLO 2 的詳細結果，這兩項相同的 III 期研究調查了 DUPIXENT 在單藥治療中的療效。這些數據也同時發表在《新英格蘭醫學雜誌》。

These were the first large pivotal studies where systemic investigational therapy demonstrated significant reduction in the signs and symptoms of atopic dermatitis, with an average reduction in skin scores of about 70%, accompanied by a marked reduction in the usually unrelenting itch associated with this disease, and almost 40% of these patients achieving clearing or near clearing of their skin lesions. Unlike other immune-modulating therapy, there was no evidence of increasing immunosuppression. And the most common adverse events in the two trials were injection site reactions and conjunctivitis.

這些是首批大型關鍵性研究，其中系統性研究療法顯著減輕了異位性皮膚炎的體徵和症狀，皮膚評分平均降低了約 70%，同時顯著減輕了與該疾病相關的通常持續不斷的瘙癢，近 40% 的患者實現了皮膚病變的清除或接近清除。與其他免疫調節療法不同，沒有證據顯示該療法會增加免疫抑制。這兩項試驗中最常見的不良事件是注射部位反應和結膜炎。

We were encouraged by the excitement with which these data were received by the physician community, as well as by patients. And we believe that this speaks to the current unmet need and frustration with currently available therapies for this severely debilitating disease.

這些數據受到了醫生群體和患者的熱烈歡迎，這令我們倍感鼓舞。我們認為，這反映了目前針對這種嚴重致殘性疾病的未滿足需求和現有療法的不足之處。

As Len mentioned, our BLA for DUPIXENT for the treatment of adults with moderate to severe atopic dermatitis is currently under FDA review and has been given priority review status and an action date of March 29, 2017. While the SOLO studies were in the monotherapy setting, we've also reported positive one-year top-line data from the CHRONOS Phase III study, which exploreD DUPIXENT in combination with topical corticosteroids. The safety and efficacy findings from the long-term CHRONOS study were consistent with those observed in SOLO 1 and 2.

正如 Len 所提到的，我們用於治療中度至重度異位性皮膚炎成人患者的 DUPIXENT 的生物製品許可申請 (BLA) 目前正在接受 FDA 的審查，並已獲得優先審查資格，審批日期為 2017 年 3 月 29 日。雖然 SOLO 研究是在單藥治療環境下進行的，但我們也報告了 CHRONOS III 期研究的積極一年的初步數據，該研究探索了 DUPIXENT 與局部皮質類固醇聯合用藥的情況。長期 CHRONOS 研究的安全性和有效性結果與 SOLO 1 和 2 中觀察到的結果一致。

I'm also pleased to share that LIBERTY AD CAFE, a Phase III Study of DUPIXENT with common topical corticosteroids in adult patients with severe atopic dermatitis who are not adequately controlled with, or are intolerant to, or ineligible for, oral cyclosporin is now fully enrolled. We, along with our collaborator, Sanofi, expect to complete the regulatory submission in Europe and Japan in the fourth quarter of 2016.

我也很高興地宣布，LIBERTY AD CAFE 是一項 III 期研究，旨在評估 DUPIXENT 與常用外用皮質類固醇聯合治療對嚴重異位性皮膚炎成年患者（這些患者無法透過口服環孢素得到充分控制、不耐受或不適合口服環孢素）的療效，目前該研究已完成全部招募。我們與合作夥伴賽諾菲預計將於 2016 年第四季完成在歐洲和日本的監管申報。

We also plan to initiate a Phase III study in the pediatric severe atopic dermatitis population in the first quarter of 2017 in patients between the ages of 12 and 17. We are pleased that, similar to the adult indication, DUPIXENT has received breakthrough designation for the treatment of pediatric patients with moderate to severe atopic dermatitis.

我們也計劃於 2017 年第一季啟動一項針對 12 至 17 歲兒童重度異位性皮膚炎患者的 III 期研究。我們很高興地看到，與成人適應症類似，DUPIXENT 獲得了治療中度至重度異位性皮膚炎兒科患者的突破性療法認定。

While atopic dermatitis is the most advanced indication in development for DUPIXENT, we are making headway with our asthma program, as well. We have previously announced positive results from our first pivotal study of uncontrolled persistent asthma, despite treatment with inhaled steroids and long-acting beta agonists. As a reminder, these data demonstrated improvements in both lung function, as measured by FEV, and exacerbations in all patients regardless of baseline eosinophil status.

雖然異位性皮膚炎是 DUPIXENT 目前研發進展最快的適應症，但我們在氣喘治療方面也取得了進展。我們先前已宣布，儘管使用吸入性類固醇和長效β受體激動劑治療，但無法控制的持續性氣喘的首個關鍵性研究取得了積極成果。需要提醒的是，這些數據表明，無論基線嗜酸性粒細胞狀態如何，所有患者的肺功能（以 FEV 衡量）和病情惡化均有所改善。

There was a 15% improvement above placebo in FEV1 and a 75% reduction in exacerbations in the overall population treated with the 300-milligram every two week dose. The most common adverse event associated with treatment in this study was injection site reaction.

與安慰劑相比，接受每兩週一次 300 毫克劑量治療的總體人群的 FEV1 改善了 15%，病情加重減少了 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 September, we announced completion of enrollment in LIBERTY ASTHMA QUEST, which is our confirmatory Phase III pivotal study of DUPIXENT in this indication. The primary end point of this study is at 52 weeks, and we, therefore, expect to make a regulatory submission in the US towards the end of 2017. We also expect to initiate a Phase III study in pediatric asthma patients in early 2017.

9 月，我們宣布 LIBERTY ASTHMA QUEST 的受試者招募工作已完成，這是我們針對 DUPIXENT 治療該適應症的 III 期關鍵性驗證研究。本研究的主要終點是 52 週，因此，我們預計將於 2017 年底在美國提交監管申請。我們也計劃於 2017 年初啟動一項針對兒童氣​​喘患者的 III 期研究。

We are also exploring the use of DUPIXENT in several other allergic indications, such as nasal polyps, where we expect to initiate a Phase III study early next year, and in eosinophil where we are currently in a Phase II.

我們也正在探索 DUPIXENT 在其他幾種過敏性疾病中的應用，例如鼻息肉，我們預計將於明年初啟動 III 期研究；以及嗜酸性粒細胞增多症，我們目前正在進行 II 期研究。

Turning to fasinumab, our nerve growth factory antibody for pain, in October we provided an update on this program. Following the observation of a case of rapidly progressing osteoarthritis in a patient receiving high dose fasinumab, who had a history of advanced osteoarthritis of the knee, the FDA placed our Phase II study in chronic lower back pain patients on clinical hold. This event prompted an unplanned interim analysis study, which had already completed 70% of its targeted enrollment.

關於我們用於治療疼痛的神經生長因子抗體 fasinumab，我們在 10 月提供了該計畫的最新進展。在觀察到一名接受高劑量法西單抗治療的患者出現骨關節炎快速進展的病例後（該患者有膝關節晚期骨關節炎病史），FDA暫停了我們針對慢性腰痛患者的II期研究。這一事件促使開展了一項計劃外的中期分析研究，該研究已完成其目標招募人數的 70%。

The unplanned analysis showed clear evidence of efficacy with improvement in pain scores in all fasinumab groups compared to placebo at the 8- and 12-week time points, with P-value of less than 0.01. Preliminary safety results were also generally consistent with those observed previously with its class. The FDA has since communicated that we can continue development of fasinumab in chronic lower back pain by excluding patients who have advanced osteoarthritis.

非計劃分析顯示，與安慰劑組相比，所有 fasinumab 組在 8 週和 12 週時間點的疼痛評分均有明顯改善，療效有明確證據，P 值小於 0.01。初步安全性結果也與先前觀察到的同類產品的結果基本一致。FDA 隨後表示，我們可以繼續開發 fasinumab 用於治療慢性腰痛，但需排除晚期骨關節炎的患者。

We're also continuing our pivotal program in osteoarthritis with final design elements still receiving regulatory feedback. The fasinumab program will contain safety data from approximately 10,000 patients overall.

我們也持續推進骨關節炎的關鍵性項目，最終設計方案仍在接受監管部門的回饋。fasinumab 計畫將包含來自約 10,000 名患者的安全資料。

Moving to PRALUENT, the recent news on the discontinuation of development of bococizumab obviously has a major impact on the PCSK9 landscape. This further underscores the very high bar in terms of safety and efficacy for this class. This example also highlights to us the value of our fully human VelocImmune-based antibody technology.

再來看 PRALUENT，最近 bococizumab 停止開發的消息顯然對 PCSK9 領域產生了重大影響。這進一步凸顯了此類藥物在安全性和有效性方面的高標準。這個例子也向我們突顯了我們基於全人源 VelocImmune 抗體技術的價值。

In terms of our PRALUENT program, our 18,000 patient ODYSSEY outcome study remains ongoing. We expect the second interim analysis for futility and overwhelming efficacy by the end of this month.

就我們的 PRALUENT 計畫而言，我們針對 18,000 名患者的 ODYSSEY 結果研究仍在進行中。我們預計本月底公佈第二次中期分析結果，以確定療效是否顯著以及是否具有壓倒性優勢。

We and our collaborator, Sanofi, have also completed regulatory submissions for the once monthly dosing formulation of PRALUENT in the Europe and Japan territories, as well as in the United States, where we have been granted an FDA action date of January 24, 2017.

我們和我們的合作夥伴賽諾菲也已完成了 PRALUENT 每月一次給藥製劑在歐洲、日本以及美國的監管申報，我們已獲得 FDA 於 2017 年 1 月 24 日作出的審批決定。

Our immuno-oncology program continues to advance and expand. We believe that these are still early days in the area of immuno-oncology with the collective knowledge of this field evolving rapidly and the competitive landscape changing continuously. Evidence of this includes the recent surprising failure of the market leading PD-1 antibody in first-line lung cancer.

我們的免疫腫瘤學課程持續進步和擴展。我們認為，免疫腫瘤學領域仍處於早期階段，該領域的集體知識正在迅速發展，競爭格局也在不斷變化。這方面的證據包括市場領先的 PD-1 抗體在肺癌一線治療中出乎意料的失敗。

Regarding our PD-1 program, our potentially pivotal study in cutaneous squamous cell carcinoma is ongoing and we plan to announce additional studies in the near future. In addition, we are also studying PD-1 in combination with our bi-specific CD20 by CD3 molecule.

關於我們的 PD-1 項目，我們正在進行一項可能具有關鍵意義的皮膚鱗狀細胞癌研究，並計劃在不久的將來宣布其他研究。此外，我們也正在研究 PD-1 與我們的雙特異性 CD20/CD3 分子的聯合作用。

Later this year at the American Society of Hematology, or ASH, conference, we will be presenting monotherapy data from the CD20 by CD3 program. Lastly, we plan to advance Regeneron 3767 an antibody to LAG3 into clinical development by the end of 2016.

今年晚些時候，我們將在美國血液學會（ASH）會議上展示 CD20 by CD3 計畫的單藥治療數據。最後，我們計劃在 2016 年底前將 Regeneron 3767（一種針對 LAG3 的抗體）推進到臨床開發階段。

In October, we announced top-line results from a Phase II combination study of EYLEA with rinucumab, our PDGF receptor antibody in wet age-related macular degeneration, or wet AMD, where the data demonstrated no improvement in best corrected visual acuity, or BCVA, the primary end point of the study versus EYLEA alone. We think these study results demonstrate the high hurdle that has been set by the well-established efficacy and safety of EYLEA.

10 月，我們公佈了 EYLEA 與 rinucumab（我們的 PDGF 受體抗體）聯合治療濕性老年性黃斑部病變（濕性 AMD）的 II 期聯合研究的主要結果，數據顯示，與單獨使用 EYLEA 相比，最佳矯正視力（BCVA，該研究的主要終點）沒有改善。我們認為這些研究結果表明，EYLEA 的療效和安全性已得到充分證實，這為其他產品樹立了很高的門檻。

That said, we are looking for ways in which we can strengthen our EYLEA franchise. To that end we are conducting a Phase II Study of EYLEA in a co-formulated combination with nesvacumab, our antibody to ANG-2 in AMD and DME. The DME study is fully enrolled while the study in wet AMD continues to enroll patients. We are also exploring longer acting approaches in this class.

也就是說，我們正在尋找能夠加強 EYLEA 品牌的方法。為此，我們正在進行 EYLEA 與 nesvacumab（一種針對 AMD 和 DME 的 ANG-2 抗體）聯合用藥的 II 期研究。DME 研究已完成招募，而濕性 AMD 研究仍在繼續招募患者。本課程中，我們也將探索作用時間較長的方法。

And with that summary, let me turn the call over to Bob Terifay.

總結完畢，現在讓我把電話交給鮑伯‧特里費。

Thank you, George, and good morning, everyone. Third-quarter US EYLEA, or aflibercept, net sales grew 16% year over year. Net US EYLEA sales in the third quarter were $854 million and year-to-date sales were $2.5 billion.

謝謝你，喬治，大家早安。第三季美國EYLEA（阿柏西普）淨銷售額年增16%。安理國際第三季在美國的淨銷售額為 8.54 億美元，今年迄今的銷售額為 25 億美元。

Net ex-US EYLEA sales in the third quarter were $471 million, which represents 27% year-over-year growth, unadjusted for currency fluctuations. Net ex-US year-to-date sales were $1.4 billion.

第三季安怡（EYLEA）除美國以外的淨銷售額為 4.71 億美元，年增 27%（未考慮匯率波動）。今年迄今為止，除美國以外，淨銷售額為 14 億美元。

EYLEA is the market leading product among FDA approved anti-VEGF agents for all of its approved indications in the United States. In the US, we are seeing increased competitor discounts and rebates. We are carefully assessing these actions.

在美國，EYLEA 是 FDA 批准的抗 VEGF 藥物中，針對其所有核准適應症的市場領先產品。在美國，我們看到競爭對手的折扣和回饋越來越多。我們正在認真評估這些行動。

As I'm sure you are well aware, there's a pending proposal from the Centers for Medicare and Medicare Services regarding physician reimbursement for physician administered Medicare Part B, or buy-and-build drugs. We've worked hard on the policy and legislative front on this issue and will be prepared to respond on the commercial front, as needed, to make sure that patients continue to have full and complete access to EYLEA.

我相信您也清楚，醫療保險和醫療補助服務中心正在審議一項關於醫生報銷由醫生管理的醫療保險 B 部分（即“購買和構建”藥物）的提案。我們在政策和立法方面為此問題付出了巨大努力，並將根據需要在商業方面做好準備，以確保患者繼續獲得 EYLEA 的全面和完整使用權。

Turning now to PRALUENT, or alirocumab, as reported by Sanofi, net sales in the third quarter were $38 million worldwide, with the US accounting for $32 million of the total. Sales data and IMS total prescription data indicate that PRALUENT and evolocumab market share are roughly 50/50 in the United States. As reported by IMS, US total prescriptions for PRALUENT increased sequentially 60% versus second quarter 2016.

現在來看 PRALUENT（或稱 alirocumab），根據賽諾菲公司報告，第三季全球淨銷售額為 3,800 萬美元，其中美國市場佔 3,200 萬美元。銷售數據和 IMS 總處方數據顯示，PRALUENT 和 evolocumab 在美國的市佔率大致為 50/50。根據 IMS 報道，美國 PRALUENT 處方總量較 2016 年第二季季增 60%。

The challenge for the PCSK9 inhibitor class continues to be the significant reimbursement hurdles for the physicians' offices and patients, resulting in a low volume of prescriptions being dispensed. This has resulted in physicians' offices reserving their initial prescriptions to a limited pool of patients. We continue to focus our efforts in improving access and improving the prescription process through the payers and the specialty pharmacies.

PCSK9 抑制劑類藥物面臨的挑戰仍然是醫生診所和患者在報銷方面遇到的重大障礙，導致處方量較低。這導致醫生診所只向有限數量的患者提供首次處方。我們將繼續致力於透過支付方和專科藥局來改善藥品取得途徑和處方流程。

We are gradually seeing more payers loosen their utilization management criteria, including removing the requirement for prior ezetimibe therapy. In addition, we are now seeing some patients shortening the number of months that a patient needs to be on a maximally tolerated statin therapy and eliminating a specialist-only prescribing or consultation requirement. Others have streamlined the prior authorization process. ODYSSEY outcomes status, if positive, are anticipated to be a key driver in shaping the future success of PRALUENT.

我們逐漸看到越來越多的支付方放寬了其使用管理標準，包括取消了先前接受依折麥布治療的要求。此外，我們現在看到一些患者縮短了接受最大耐受劑量他汀類藥物治療所需的時間，並且取消了僅限專科醫生開立處方或諮詢的要求。其他人則簡化了事先授權流程。ODYSSEY 試驗結果（如果為陽性）預計將成為塑造 PRALUENT 未來成功的關鍵驅動因素。

Outside of the United States, PRALUENT was approved in the EU in September of 2015 with the product now approved in 41 countries. Reimbursement discussions are currently under way with several governments across Europe. Positive reimbursement decisions have been issued in the UK, Spain, Norway, and the Netherlands. It still remains a challenging reimbursement situation with some countries awaiting cardiovascular outcomes data.

在美國以外，PRALUENT 於 2015 年 9 月在歐盟獲得批准，目前該產品已在 41 個國家獲得批准。目前正與歐洲多個國家的政府就報銷事宜進行磋商。英國、西班牙、挪威和荷蘭均已作出積極的報銷決定。目前，一些國家仍在等待心血管疾病治療結果數據，因此健保報銷問題仍充滿挑戰。

We continue to plan for the potential launch of sarilumab in the United States. As an example, we have a major presence at the upcoming American College of Rheumatology meeting this month in Washington D.C. We'll be presenting data from our MONARCH Study of sarilumab as monotherapy in patients who are DMARD responders, as well as subset analyses from our pivotal US registrational studies. We'll have a display floor presence, highlighting the central role of IL-6 in rheumatoid arthritis.

我們仍在為在美國推出 sarilumab 做準備。例如，我們將在本月於華盛頓特區舉行的美國風濕病學會會議上重點展示我們的 MONARCH 研究數據，該研究評估了 sarilumab 作為 DMARD 應答患者的單藥治療效果，以及我們關鍵性美國註冊研究的亞組分析。我們將在展廳內進行展示，重點介紹 IL-6 在類風濕性關節炎中的核心作用。

The European marketing authorization application for sarilumab is currently under review by the European Medicines Agency, with a potential decision on the application expected in mid 2017. Co-promotion decisions for Europe and other ex-US countries will be made over time.

sarilumab 的歐洲上市許可申請目前正在接受歐洲藥品管理局的審查，預計將於 2017 年年中做出決定。歐洲和其他非美國國家的聯合推廣決定將分階段做出。

We're currently preparing for DUPIXENT or dupilumab commercialization with an FDA PDUFA date of March 29, 2017. We will be co-promoting DUPIXENT with Sanofi Genzyme in the United States. Co-promotion decisions for other countries will be made at a later date.

我們目前正在為DUPIXENT或dupilumab的商業化做準備，FDA的PDUFA日期為2017年3月29日。我們將與賽諾菲健贊在美國共同推廣DUPIXENT。其他國家的聯合推廣決定將在稍後做出。

We are aware that ICER, payers and pharmacy benefits managers are proactively evaluating the cost effectiveness of emerging therapies for atopic dermatitis in the United States. We want to take a moment to discuss how we are thinking about the DUPIXENT commercial opportunity, which differs in many important respects from the situation we faced with PRALUENT.

我們了解到，ICER、支付方和藥房福利管理機構正在積極評估美國新興異位性皮膚炎療法的成本效益。我們想花點時間討論一下我們對 DUPIXENT 商業機會的看法，這與我們之前在 PRALUENT 上遇到的情況有很多重要之處。

DUPIXENT has already demonstrated efficacy on the most important outcomes -- consistent efficacy on rash severity, itching, and quality of life measures. In the United States, there are 1.6 million patients with uncontrolled moderate to severe atopic dermatitis, the majority of which will not likely receive DUPIXENT therapy. We estimate that approximately 300,000 of these patients have exhausted all approved therapies and have failed or are unable to tolerate unapproved use of immunosuppressant therapies.

DUPIXENT 已在最重要的結果方面證明了其療效——在皮疹嚴重程度、瘙癢和生活品質指標方面具有持續的療效。在美國，有 160 萬名患者患有無法控制的中度至重度異位性皮膚炎，其中大多數患者可能不會接受 DUPIXENT 治療。我們估計，這些患者中約有 30 萬名已經用盡了所有批准的療法，並且對未經批准的免疫抑制劑療法無效或無法耐受。

Many of these advanced patients are suffering from a host of related issues, including sleep disturbances, anxiety, and depression. These atopic dermatitis patients should not be denied therapy.

許多晚期患者都患有一系列相關問題，包括睡眠障礙、焦慮和憂鬱。不應拒絕為這些異位性皮膚炎患者提供治療。

We hope payers and insurers will provide appropriate and timely access to DUPIXENT, should it be approved. And that patients will not have to step through unapproved immunosuppressant therapy, many of which have black box warnings. We plan to work closely with all stakeholders, including patients, physicians, and payers to achieve this goal.

我們希望，如果DUPIXENT獲得批准，支付方和保險公司能夠提供適當且及時的用藥途徑。這樣一來，患者就不必經歷未經批准的免疫抑制劑治療，其中許多藥物都帶有黑框警告。我們計劃與包括患者、醫生和支付方在內的所有利益相關者密切合作，以實現這一目標。

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. Regeneron posted strong financial results in the third quarter of 2016 as well as entered into two new exciting collaborations. We are also lowering and tightening full-year 2016 guidance on non-GAAP unreimbursed R&D, non-GAAP SG&A, our effective tax rate and capital expenditures. Let me start with our top-line third-quarter earnings.

謝謝你，鮑勃，早安。2016 年第三季度，Regeneron 公司公佈了強勁的財務業績，並達成了兩項令人興奮的新合作。我們同時下調並收緊了 2016 年全年非 GAAP 未報銷研發費用、非 GAAP 銷售、一般及行政費用、有效稅率和資本支出的預期。讓我先從我們第三季的主要獲利情況說起。

In the third quarter of 2016, non-GAAP net income was $365 million and non-GAAP net income per diluted share was $3.13. This represents an increase of 32% in both non-GAAP net income per diluted share as well as non-GAAP net income in the third-quarter 2016 compared to the third quarter of 2015.

2016 年第三季度，非 GAAP 淨收入為 3.65 億美元，非 GAAP 每股稀釋淨收入為 3.13 美元。與 2015 年第三季相比，2016 年第三季非 GAAP 每股稀釋淨收入和非 GAAP 淨收入均成長了 32%。

Regeneron's third-quarter 2016 non-GAAP net income primarily excludes non-cash share-based compensation expense, and the $25 million up front payment made in connection with our third-quarter 2016 license and collaboration agreement with Adicet, and includes the income tax effect of these non-GAAP reconciling items. A full reconciliation of GAAP to non-GAAP earnings is set forth in our earnings release.

Regeneron 2016 年第三季非 GAAP 淨收入主要不包括非現金股份支付費用，以及根據我們 2016 年第三季與 Adicet 的許可和合作協議支付的 2,500 萬美元預付款，但包括這些非 GAAP 調整專案的所得稅影響。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 third quarter of 2016 were $1.2 billion, which represents year-over-year growth of 7% over the third quarter of 2015. Net product sales were $857 million in the third quarter of 2016 compared to $738 million in the third quarter of 2015.

2016 年第三季總營收為 12 億美元，比 2015 年第三季年增 7%。2016 年第三季淨產品銷售額為 8.57 億美元，而 2015 年第三季為 7.38 億美元。

EYLEA US net product sales were $854 million compared to $734 million in the third quarter of 2015, representing 16% year-over-year growth. Sequential quarter-over-quarter growth was approximately 3%. During the third quarter 2016, EYLEA experienced a slight increase in US distributer inventory levels as compared to the second quarter of 2016, but continues to be within our normal one- to two-week targeted range.

EYLEA 美國淨產品銷售額為 8.54 億美元，而 2015 年第三季為 7.34 億美元，年成長 16%。環比增長約 3%。2016 年第三季度，安怡美國分銷商的庫存水準與 2016 年第二季度相比略有上升，但仍在我們正常的一到兩週的目標範圍內。

As mentioned in our press release issued this morning, we are tightening our full-year 2016 US EYLEA net sales guidance to be year-over-year growth of 23% to 25%. Ex-US EYLEA sales, where product revenue is recorded by our collaborate Bayer, were $471 million in the third quarter of 2016 compared to $371 million in the third quarter of 2015, representing a 27% increase on a reported basis. On an operational basis, or constant currency basis, sales increased approximately 25%.

正如我們今天早上發布的新聞稿中所述，我們將 2016 年全年美國安樂淨銷售額預期收緊，預計將年增 23% 至 25%。2016 年第三季度，EYLEA 在美國以外的銷售額（產品收入由我們的合作夥伴拜耳記錄）為 4.71 億美元，而 2015 年第三季度為 3.71 億美元，按報告數據計算增長了 27%。以營運成本或固定匯率計算，銷售額成長了約 25%。

In the third quarter of 2016 Regeneron recognized $171 million from our share of net profits from EYLEA sales outside the US. Total Bayer collaboration revenue for the third quarter 2016 was $191 million.

2016 年第三季度，Regeneron 從美國以外地區 EYLEA 的銷售淨利潤中確認了 1.71 億美元的收入。2016 年第三季拜耳合作總營收為 1.91 億美元。

Turning now to our Sanofi collaboration, total Sanofi collaboration revenue was $144 million for the third quarter 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 the commercialization of antibodies.

現在來說說我們與賽諾菲的合作，2016 年第三季與賽諾菲的合作總收入為 1.44 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，以及我們與抗體商業化相關的利潤或虧損份額。

In the third quarter of 2016, our share of the collaboration's losses in connection with commercialization of antibodies, which includes PRALUENT and pre-commercialization activities and costs in connection with sarilumab and DUPIXENT, was $112 million, which can be found in table 4 of our earnings release. Netted within these collaboration losses were the global sales of PRALUENT as recognized by our collaborator, Sanofi, of $38 million for the third quarter of 2016.

2016 年第三季度，我們在抗體商業化合作中承擔的虧損份額為 1.12 億美元，其中包括 PRALUENT 以及與 sarilumab 和 DUPIXENT 相關的商業化前活動和成本，詳情請參見我們的收益報告表 4。在這些合作損失中，包括我們的合作夥伴賽諾菲確認的 PRALUENT 在 2016 年第三季的全球銷售額 3,800 萬美元。

Before moving to expenses I'd like to highlight two third-quarter business development transactions. The first is the collaboration we entered into with Teva to develop and commercialize our NGF antibody fasinumab. Under the terms of agreement Teva paid Regeneron a $250 million up-front payment, and we will equally share on an ongoing basis R&D expenses of approximately $1 billion under a global development plan.

在介紹費用之前，我想先重點介紹第三季的兩項業務發展交易。首先是我們與梯瓦製藥公司合作開發和商業化我們的 NGF 抗體 fasinumab。根據協議條款，梯瓦向再生元支付了 2.5 億美元的預付款，我們將根據全球發展計劃，持續平均分擔約 10 億美元的研發費用。

We plan to ratably recognize the up-front payment as revenue over the related performance period. The signing of this agreement did not have a material P&L impact on the third quarter of 2016. As a reminder, the intellectual property associated with our late-stage pipeline, including fasinumab, has been migrated offshore; thus, expenses and revenues associated with the program will be recognized in foreign jurisdictions with tax rates lower than the US federal statutory rate.

我們計劃在相關業績期間內按比例確認預付款為收入。該協議的簽署對 2016 年第三季的損益表並沒有產生重大影響。提醒各位，與我們的後期研發管線（包括 fasinumab）相關的智慧財產權已轉移到海外；因此，與該項目相關的支出和收入將在稅率低於美國聯邦法定稅率的外國司法管轄區確認。

The other 2016 third-quarter business development transaction was a collaboration with Adicet, which will allow us to discover and develop engineered next-generation immune cell therapeutics. In accordance with this agreement, we paid Adicet a $25 million up-front payment in the third quarter 2016, which we have recorded as GAAP R&D expense in are consolidated statement of operations but have excluded from our non-GAAP net income.

2016 年第三季另一項業務發展交易是與 Adicet 的合作，這將使我們能夠發現和開發工程化的下一代免疫細胞療法。根據該協議，我們在 2016 年第三季向 Adicet 支付了 2,500 萬美元的預付款，我們已將其作為 GAAP 研發費用計入合併經營報表，但已將其從非 GAAP 淨收入中排除。

Turning now to expenses, non-GAAP R&D expense, which is calculated as the total GAAP R&D expense less R&D non-cash share-based compensation expense, as well as the up-front payment we made to collaborator Adicet, was $437 million for the third quarter of 2016. Our non-GAAP unreimbursed R&D expense, which is calculated as the total non-GAAP R&D expense less R&D reimbursements from our collaborators, was $256 million for the three months ended September 30, 2016. Our press release includes all of the information that is required to calculate unreimbursed non-GAAP R&D expense.

現在來看費用，非GAAP研發費用（計算方法為GAAP研發費用總額減去研發非現金股份支付費用，以及我們向合作方Adicet支付的預付款）在2016年第三季為4.37億美元。截至 2016 年 9 月 30 日止的三個月內，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 2.56 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。

As a result of the recently executed collaboration with Teva regarding fasinumab, we are lowering and tightening our full-year 2016 guidance for non-GAAP unreimbursed R&D to be in the range of $945 million to $975 million from our previous guidance range of $970 million to just over $1 billion.

由於最近與梯瓦製藥就法西單抗達成了合作，我們將 2016 年全年非 GAAP 未報銷研發資金的預期從之前的 9.7 億美元至略高於 10 億美元下調並收緊至 9.45 億美元至 9.75 億美元。

Non-GAAP SG&A expense was $221 million for the third quarter 2016. We are tightening and lowering our full-year 2016 guidance for non-GAAP SG&A to $965 million to $995 million from our previous guidance range of $980 million to $1.02 billion.

2016 年第三季非 GAAP 銷售、一般及行政費用為 2.21 億美元。我們將 2016 年全年非 GAAP 銷售、一般及行政費用預期從先前的 9.8 億美元至 10.2 億美元下調至 9.65 億美元至 9.95 億美元。

Note that even after lowering and tightening our full-year guidance, we do not expect to see any material pre-launch cost savings from the PDUFA delay of sarilumab. We will be co-promoting sarilumab with Sanofi Genzyme, and our salesforce is already on board. And, as you heard earlier from Bob Terifay, we continue to prepare for the launch in anticipation of the resolution of matters with the FDA.

請注意，即使在降低和收緊全年預期之後，我們也不認為因 PDUFA 延遲上市 sarilumab 而帶來任何實質性的上市前成本節約。我們將與賽諾菲健贊共同推廣 sarilumab，我們的銷售團隊已經做好準備。正如您之前從鮑勃·特里費那裡聽到的那樣，我們將繼續為產品上市做準備，並期待與美國食品藥物管理局（FDA）的問題得到解決。

Sanofi reimbursement of Regeneron commercialization related expenses, a line item found within Sanofi collaboration revenue, was $66 million for the third quarter 2016. We are tightening our full-year 2016 guidance of Sanofi reimbursement of Regeneron commercialization related expenses to be in the range of $310 million and $335 million from $310 million to $340 million.

2016 年第三季度，賽諾菲向 Regeneron 支付的與商業化相關的費用（該費用包含在賽諾菲合作收入中）為 6,600 萬美元。我們將 2016 年全年賽諾菲 Regeneron 商業化相關費用的報銷預期從 3.1 億美元至 3.4 億美元收緊至 3.1 億美元至 3.35 億美元。

Turning now to taxes, our effective tax rate for the third quarter 2016 was 27.6% as compared to 46.5% in the third quarter of 2015. This decrease was primarily due to the impact of changes in the geographic mix of earnings, inclusion of the tax benefit of share-based compensation, and the impact of a domestic manufacturing deduction as compared to the same quarter of last year, as well as the discrete impact to this quarter of a change in our assessment of reserves for uncertain tax positions.

現在來說說稅收，2016 年第三季的實際稅率為 27.6%，而 2015 年第三季的實際稅率為 46.5%。這一下降主要是由於收益地域構成變化的影響、計入股份支付的稅收優惠以及與去年同期相比國內製造業扣除的影響，以及我們對不確定稅務事項準備金評估的變化對本季度的單獨影響。

For 2016 we are lowering and tightening guidance for our full-year GAAP effective tax rate to be 29% to 33% from the previously provided range of 33% to 41%. Our capital expenditures for the nine months ended September 30, 2016 were $361 million.

對於 2016 年，我們將全年 GAAP 有效稅率的指導範圍從先前提供的 33% 至 41% 下調並收緊至 29% 至 33%。截至 2016 年 9 月 30 日的九個月，我們的資本支出為 3.61 億美元。

For the full-year 2016, we are lowering and tightening our guidance for capital expenditures to be in the range of $480 million to $510 million from the previously provided range of $480 million to $530 million. 2016 capital expenditures primarily include costs in connection with renovations of our Limerick, Ireland manufacturing facility, tenant improvement and associated costs at our Tarrytown, New York facilities, renovations and additions to our Rensselaer, New York manufacturing facilities, and the purchase of an office building near our Rennselaer manufacturing facility.

對於 2016 年全年，我們將資本支出指引範圍從先前提供的 4.8 億美元至 5.3 億美元下調並收緊至 4.8 億美元至 5.1 億美元。2016 年資本支出主要包括：愛爾蘭利默里克製造工廠的翻新費用、紐約州塔里敦工廠的租戶裝修及相關費用、紐約州倫斯勒製造工廠的翻新和擴建費用，以及在倫斯勒製造工廠附近購買辦公大樓的費用。

We ended the third quarter of 2016 with cash and marketable securities of $2.2 billion which includes the Teva up-front payment of $250 million. As we have reported in previous quarters, we have opportunistically reduced a number of warrants that we issued in 2011 in connection with our convertible debt issuance through repurchases from the warrant counterparties. Depending on market and other conditions, we may spend up to $450 million to repurchase or settle these outstanding warrants.

截至 2016 年第三季末，我們持有現金和有價證券 22 億美元，其中包括 Teva 預付的 2.5 億美元。正如我們在前幾季所報告的那樣，我們抓住機會，透過從認股權證交易對手方回購的方式，減少了我們在 2011 年發行可轉換債券時發行的一些認股權證。根據市場和其他情況，我們可能會花費高達 4.5 億美元來回購或結算這些未償付的認股權證。

With that, I'd now like to turn the call over to Michael.

那麼，我現在想把電話交給麥可。

Thank you, Bob. Before turning it over to Q&A let me remind everyone to please keep your questions to a single question to allow for the most number of people to have a turn. With that, operator, can we please open it up for Q&A?

謝謝你，鮑伯。在進入問答環節之前，請容我提醒大家，請將問題控制在一個問題以內，以便讓更多的人有機會提問。操作員，那我們可以開始問答環節了嗎？

(Operator Instructions)

（操作說明）

Our first question comes from Robyn Karnauskas from Citigroup.

我們的第一個問題來自花旗集團的 Robyn Karnauskas。

Hi, guys. Thank you and I'll stick to the one question. If I heard you correctly, it sounded like the (inaudible) study was completed enrollment, and it's a 12-week study. So, is it possible that we could get results in the first quarter? And, if so, or when we get results, remind us how you typically release them -- press release or do we have to wait for a conference? And maybe some color and expectations around that. Thank you.

嗨，大家好。謝謝，我就問這一個問題。如果我沒聽錯的話，這項（聽不清楚的）研究似乎已經完成了招募，而且這是一項為期 12 週的研究。那麼，我們有可能在第一季就取得成果嗎？如果是這樣，或者當我們得到結果時，請提醒我們你們通常如何發布結果——發布新聞稿還是我們需要等待會議？或許還可以加入一些色彩和相關的期待。謝謝。

First, since it's talking about timing, we really don't give guidance on timing. And as we have with our PDGF we typically look at this and give the top-line press releases, is our typical practice.

首先，既然是在討論時間安排，我們其實並沒有提供時間安排的指導。就像我們對待 PDGF 一樣，我們通常會關注此事並發布概要新聞稿，這是我們的慣例。

But one general comment, Robyn. We would say that -- and George might want to amplify -- EYLEA is a tough bar, and we're constantly looking to try and improve on that. So, when we get the data we certainly will give you a top-line assessment.

不過，羅賓，我還有一點要說。我們想說——喬治可能還想強調——EYLEA 是一個很高的標準，我們一直在努力超越它。所以，當我們拿到數據後，一定會給您初步的評估。

Our next question comes from Terence Flynn from Goldman Sachs.

下一個問題來自高盛的特倫斯·弗林。

Hi, thanks for taking the question. I was just wondering -- two parts, so, first, maybe walk us through some of the key drivers of EYLEA growth that we should consider as we head into next year here. And then, Bob, maybe just last year at this time you highlighted 2016 was shaping up to be an important investment year. Any thoughts here as we head into 2017 for the dupilumab launch? Thank you.

您好，感謝您回答這個問題。我只是想問一下——分為兩部分，首先，能否請您帶我們了解一下在展望明年時，我們應該考慮的EYLEA增長的一些關鍵驅動因素？鮑勃，也許就在去年這個時候，你還強調 2016 年將會是個重要的投資年。展望2017年dupilumab上市，大家有什麼想法？謝謝。

It's Len. I'll let Bob amplify, if he likes. But the obvious potential growth drivers for EYLEA come from demographics, aging population, more patients with diabetic eye disease. Potentially would come from market share, depending upon what continues to happen in the marketplace. There's both potential for ups and downs there. And obviously, additional indications -- diabetic retinopathy. Those are the three places where we would be focusing and looking to drive growth off of a very large base, obviously.

是倫。如果鮑伯願意，我就讓他擴音。但 EYLEA 最明顯的潛在成長動力來自人口結構變化、人口老化以及糖尿病眼疾患者增加。潛在收益可能來自市場份額，具體取決於市場接下來的發展。那裡既有可能出現機遇，也可能出現挫折。當然，還有其他症狀——糖尿病視網膜病變。顯然，我們將重點關注這三個領域，並希望在龐大的基礎上推動成長。

Terence, hi, it's Bob. We'll go out with our SG&A guidance upcoming. We're not in a position right now to talk to that. But, again, we've spent time on this call, and you've heard us previously, with regards to the excitement we have around DUPIXENT. So, with the March 29 PDUFA date coming, we need to ensure that we are ready with regards to our marketing and our sales teams and everything to be able to hit the road very quickly on that.

特倫斯，你好，我是鮑伯。我們很快就會發布銷售、管理及行政費用指引。我們現在不方便談論這個問題。但是，我們再次強調，我們在這次電話會議上花了很多時間，而且你們之前也聽到了我們談到我們對 DUPIXENT 的興奮之情。因此，隨著 3 月 29 日 PDUFA 日期的臨近，我們需要確保我們的行銷和銷售團隊以及所有相關人員都做好準備，以便能夠迅速啟動相關工作。

And, again, we're still investing behind PRALUENT as we wait for the outcomes data. And sarilumab, as I mentioned on the call, we are putting our promotional dollars behind that and our marketing and spend. And when the FDA lifts the -- we get regulatory approval on that, then we will be in a position to ensure that the product is fully supported from a marketing and sales perspective.

而且，我們仍在繼續投資 PRALUENT，等待結果數據。正如我在電話會議上提到的，我們將把推廣資金和行銷支出都投入到 sarilumab 上。當 FDA 解除限制——我們獲得監管部門的批准後，我們將能夠確保產品在行銷和銷售方面得到全面支持。

Next we have Ying Huang from Bank of America Merrill Lynch.

接下來是來自美國銀行美林證券的黃穎。

Hi, good morning. Thanks for the question. I have a question on the ODYSSEY outcome study here. We know the hurdle for overwhelming efficacy to stop the trial, has a ratio less than 0.802 with a P value 0.0001. Can you elaborate? Do you need to see consistency in every composite of the primary end point, of for composite of the primary end point? And also, can you tell us how much confidence you have in terms of being able to meet that end point by end of this month? Thank you.

您好，早安。謝謝你的提問。我有一個關於 ODYSSEY 結果研究的問題。我們知道，要達到壓倒性的療效以停止試驗，其比率必須小於 0.802，P 值為 0.0001。能詳細說明一下嗎？您是否需要看到主要終點的每個複合指標都保持一致？另外，您能否告訴我們，您對在本月底前實現該目標有多大信心？謝謝。

Yes, this is George. In some ways, this decision is out of our hands. And it's very subjective in terms of there's an independent monitoring board that, without us, is going to look at the data regardless of even if we hit the numbers that you stated in terms of for overwhelming efficacy. They have to make a decision about not only consistency and so forth, but they are going to take into account whether there's rationale and it's worth while, because maybe they want to look within this sub group or another to get the complete data set.

是的，這是喬治。在某種程度上，這個決定不由我們掌控。而且這非常主觀，因為有一個獨立的監督委員會，即使我們達到了你所說的壓倒性療效數字，他們也會在沒有我們的情況下審查數據。他們不僅要考慮一致性等等問題，還要考慮是否有合理性以及是否值得這樣做，因為他們可能想在這個子組或其他子組中找到數據，以獲得完整的數據集。

So, it's very hard to predict something like that. And, as I said, it's up to an independent data monitoring board. It's completely out of our hands. And they could simply decide, for example, if they want to follow and get more depth in one particular sub group, even though the overall population was very clear. So, the end result is I can't really answer your question because we just don't know.

所以，這類事情很難預測。正如我所說，這取決於一個獨立的數據監測委員會。這完全超出了我們的控制範圍。例如，即使整體人群的情況非常明確，他們也可以自行決定是否要繼續深入研究某個特定的子群體。所以，最終的結果是，我無法回答你的問題，因為我們根本不知道。

Next we have Chris Raymond from Raymond James.

接下來是來自 Raymond James 的 Chris Raymond。

Thanks. On sarilumab, just putting the manufacturing delay for the drug aside, there's been some news in the biologic space in inflammation recently with Amgen talking about running out of its pricing runway. And we've actually seen from some of our own work pretty strong evidence that other newer biologics have been gaining traction for some time. I wonder if you could maybe describe at a high level your views maybe of the changing landscape with respect to access and PBM market power, and how you think sarilumab, once it is ultimately approved, is positioned, not just necessarily from a clinical standpoint but how you think the commercial landscape is changing in ways that may or may not favor the drug. Thanks.

謝謝。關於 sarilumab，暫且不談該藥物的生產延誤，最近在發炎生物製劑領域有一些消息，安進公司表示其定價策略即將失效。事實上，我們自身的一些研究也提供了相當有力的證據，表明其他一些較新的生物製劑已經獲得了相當大的關注。我想請您概括地描述一下您對藥物獲取和藥品福利管理機構（PBM）市場力量變化的看法，以及您認為沙利魯單抗最終獲批後將如何定位，不僅要從臨床角度，還要從您認為商業環境的變化角度來談談，這些變化可能對該藥物有利，也可能不利。謝謝。

Sure. This is Len. At the risk of unveiling a little bit of our strategy here, but not too much of it because obviously we have to get to market, it is a tough environment, and the people who are paying the bills have seen what I would consider, in some cases, almost outrageous increases in the price of -- at least on the WAC price -- of the wholesale position costs of drugs for rheumatoid arthritis with people taking double-digit increases sometimes twice a year. To me, that suggests some sort of tone deafness in this environment.

當然。這是倫。雖然這可能會稍微洩露我們的一些策略，但不會透露太多，因為顯然我們必須進入市場，這是一個艱難的環境，而且那些付賬的人已經看到，在某些情況下，類風濕性關節炎藥物的批發價格（至少在批發採購價格方面）出現了近乎離譜的上漲，人們有時一年要承受兩次兩位數的漲幅。在我看來，這顯示這種環境存在某種程度的不協調感。

We think that we have to compete in two ways. We have to compete with a very good drug, which we think sarilumab will be. Of course we have to get over this glitch and get to market as quickly as we can, but we think that the class is doing very well. There's some data out there from the first entry in the class where monotherapy against the leading anti-TNF, the NIL-6 receptor class, performed better.

我們認為我們必須在兩個方面展開競爭。我們必須與一種非常優秀的藥物競爭，我們認為沙利魯單抗就是這樣一種藥物。當然，我們必須克服這個小問題，盡快將產品推向市場，但我們認為這個系列目前發展得非常好。已有數據顯示，該類藥物的首款產品，針對領先的抗 TNF 藥物 NIL-6 受體類藥物的單藥治療效果更佳。

And there are some people who simply don't like to take methotrexate. We have data of our own, which probably won't be in our first filing, similar types of results with outperforming in monotherapy.

還有一些人就是不喜歡服用甲胺蝶呤。我們也有自己的數據，這些數據可能不會出現在我們的第一份文件中，這些數據也顯示出類似的單藥治療優於其他療法的效果。

But giving a solid entry with good properties is not going to be enough here. And we have to compete with an offering that payers will find attractive. I think Regeneron is willing to break some of the mold here. And now I'm getting some hints from my colleagues that I've probably said enough so I'll leave it at that.

但是，僅僅提供一份擁有良好屬性的可靠報價是不夠的。我們必須提供能夠吸引付費用戶的產品和服務，才能與之競爭。我認為再生元公司願意打破一些常規做法。現在我的同事暗示我可能說得夠多了，所以我就此打住吧。

It's Bob. I think it's important, though, also to keep in mind that the market has been characterized by a significant amount of TNF cycling. And the reality is, after a patient receives one TNF inhibitor, if they move to a second, we see diminishing efficacy over time.

是鮑伯。不過，我認為同樣重要的是要記住，市場一直存在著大量的 TNF 循環現象。而現實情況是，患者接受一種 TNF 抑制劑治療後，如果再接受第二種，我們會發現療效會隨著時間的推移而降低。

We have an obligation from a sales and marketing perspective, when we get approved, to stop the TNF cycling. And IL-6 inhibition plays a central role in RA. It plays a role in not only the symptoms but in terms of the progression of joint damage. And we have to educate physicians on that. We're anxious to have the product get approved and get that message out there.

從銷售和行銷的角度來看，一旦獲得批准，我們就有義務停止 TNF 循環。IL-6抑制在類風濕性關節炎中扮演核心角色。它不僅影響症狀，也影響關節損傷的進展。我們必須對醫生進行這方面的教育。我們迫切希望產品能夠獲得批准，並將這項訊息傳遞給更多人。

Next we have Geoffrey Porges from Leerink Partners.

接下來是來自 Leerink Partners 的 Geoffrey Porges。

Thanks very much for the question. Perhaps a question on the manufacturing issue. It's been a week since the Sanofi conference call so I presume you both have a lot more information. Could you confirm whether the alternative fill/finish facility was included in the original BLA and whether it's straightforward to switch the fill/finish [FDUPI] to that alternative facility.

非常感謝您的提問。或許可以問一個關於生產製造方面的問題。距離賽諾菲電話會議已經過去一周了，所以我估計你們倆現在應該掌握了更多資訊。請確認原 BLA 中是否包含了備選填充/加工設施，以及將填充/加工 [FDUPI] 切換到該備選設施是否簡單。

And then, secondly, could you just tell us whether the inventory of PRALUENT, sarilumab and dupilumab, which presumably you have already pre-launched, is embargoed, or is it likely to be usable, and can you be selling PRALUENT from that inventory already? Thanks.

其次，您能否告知我們，您已預先推出的 PRALUENT、sarilumab 和 dupilumab 的庫存是否受到禁令限制，或者是否可以正常使用，以及您是否可以從該庫存中銷售 PRALUENT？謝謝。

Yes, as usual, you ask some of the best and most penetrating questions. And, as usual, we would love to give you an answer but we really are not in a position to discuss the details of discussions that are ongoing with the FDA, how they are going to be resolved, the strategy of redundancy, what's in filings, what isn't, and so on and so forth.

是的，你一如既往地提出了一些最好、最深刻的問題。像往常一樣，我們很想給您答复，但我們真的不方便討論與 FDA 正在進行的討論的細節，例如如何解決這些問題、冗餘策略、文件中包含什麼、不包含什麼等等。

We can summarize by saying that Sanofi is working very hard and they believe they can quickly remedy the deficiencies that were not related to sarilumab per se but rather some general GMP deficiencies, which they are, frankly, well on their way to remedying. Of course, we have to work with the Agency and they have to be satisfied.

我們可以總結說，賽諾菲正在非常努力地工作，他們相信能夠迅速糾正那些與 sarilumab 本身無關，而是與一些一般的 GMP 缺陷相關的不足之處，坦白說，他們正在朝著糾正這些缺陷的方向穩步前進。當然，我們必須與該機構合作，而且他們也必須滿意。

In terms of products that are already manufactured there, I think you should think that the FDA takes a risk-based approach here. They have maybe a frozen in place those things that are actually being -- assuming they don't think a plant is way out of whack and nothing can be shipped and filled -- they continue to fill and use product from that facility for approved products. It's a new product such as sarilumab which gets shut out, obviously and unfortunately.

對於已經在那裡生產的產品，我認為你應該認為FDA在這裡採取的是基於風險的方法。他們可能已經凍結了那些實際上正在發生的事情——假設他們認為工廠沒有嚴重失控，任何東西都無法運輸和填充——他們繼續從該工廠填充和使用產品來生產已批准的產品。像 sarilumab 這樣的新產品顯然會被排除在外，這很不公平，也很令人遺憾。

We are working with them on sarilumab. And we're also working with a different group on DUPIXENT, which is a breakthrough product, which has a whole different set of approaches to it. So, it's complicated. You can imagine there's a tremendous amount of work. A week seems like a long time maybe in your world but in the world of regulatory interactions and manufacturing remedies, and so on, it's still a relatively short time.

我們正在與他們合作開發 sarilumab。我們還與另一個團隊合作開發 DUPIXENT，這是一款突破性產品，它採用了一套完全不同的方法。所以，情況很複雜。你可以想像，這需要做大量的工作。在你的世界裡，一周可能看起來很長，但在監管互動和藥品生產等領域，這仍然是一段相對較短的時間。

Next we have Ronny Gal from Bernstein.

接下來是來自伯恩斯坦的羅尼·加爾。

Thank you for taking my questions. Just very quickly, following on Geoff, just looking at generic industry history here when it comes to fill/finish facilities, the cycles for improving facilities and getting product approvals is actually quite long. What gives you conviction that in this case it will be a relatively short one?

謝謝您回答我的問題。簡單來說，接著 Geoff 的話，從通用行業的歷史來看，就灌裝/包裝設施而言，改進設施和獲得產品批准的周期實際上相當長。你憑什麼確信這次案件會比較短？

And then if I could sneak a second one, 340B, there's been some discussion, reform for that program. If you can just let us know how you think, if you can just give us an update about this program and how it impacts EYLEA sales.

然後，如果我能偷偷提一下第二個，340B，已經有一些關於該計劃改革的討論。如果您能告訴我們您的想法，如果您能向我們提供此專案的最新進展以及它對安怡銷售的影響，那就太好了。

We're going to give you only the one question. The first question has to do with how do we know how quickly this is going to be remedied. We don't know how quickly it's going to be remedied for sure, obviously.

我們只會問你一個問題。第一個問題是，我們如何知道這個問題需要多久才能解決。顯然，我們無法確定這個問題需要多久才能解決。

We know how quickly, which is in a relatively short period of time, that Sanofi feels that they can get the plant in full GMP compliance. In fact, they've already brought in all sorts of efforts and resources. They've already submitted a detailed plan. They've already submitted their first or second progress reports against that plan.

我們知道賽諾菲認為他們能夠以相當短的時間讓工廠完全符合 GMP 標準。事實上，他們已經投入了各種人力物力。他們已經提交了一份詳細的計劃。他們已經根據該計劃提交了第一份或第二份進度報告。

So, we feel that the strategy is the right one and the approaches are the right one. Obviously we'll just have to work with the Agency and see how quickly they can feel comfortable that the plan is ready to go.

因此，我們認為該策略和方法都是正確的。顯然，我們只能與該機構合作，看看他們多久才能確信該計劃已經準備就緒。

Next we have Alethia Young from Credit Suisse.

接下來是來自瑞士信貸的阿萊西亞楊。

Hi, guys. Thanks for taking my question. Just one on the pediatric population. I know you quantified a little bit more about the adult, the 300,000 a day. Can you frame that in a similar nature as to the pediatric population please?

嗨，大家好。謝謝您回答我的問題。僅有一例針對兒童族群。我知道你對成年人的情況做了更詳細的量化，每天30萬。能否請您用類似兒科族群的方式來闡述？

Bob, do you want to comment at all?

鮑勃，你有什麼要補充的嗎？

I don't think we're prepared to go into the numbers in the pediatric population, especially since we just embarked on our Phase III program now.

我認為我們還沒有準備好深入探討兒科族群的具體數字，尤其是我們現在才剛開始第三階段的計畫。

Next we have Adnan Butt from RBC Capital Markets.

接下來是來自加拿大皇家銀行資本市場的阿德南·巴特。

Thanks for the question. Maybe for Bob. On EYLEA, pricing issue aside, is EYLEA growth tempering a bit? We had thought DME would be as big as AMD. What are the individual market dynamics, if you can give any color on that?

謝謝你的提問。或許是為了鮑伯。撇開定價問題不談，安禮製藥的成長是否有所放緩？我們原以為DME會像AMD一樣大。您能否就各個市場的動態提供一些細節資訊？

We have done very well with EYLEA in DME. That has been the driver of growth over the last couple of years, primarily driven by the impressive protocol T results which indicated that EYLEA was superior to Lucentis and bevacizumab on its primary end point.

我們在DME領域與EYLEA的合作非常成功。過去幾年，這一直是成長的驅動力，主要得益於令人印象深刻的 T 方案結果，該結果表明 EYLEA 在主要終點上優於 Lucentis 和貝伐珠單抗。

The challenge with continuing growth in DME is that there are a number of patients that never make it to the retinal specialist's office. They go to an ophthalmologist who do laser therapy -- laser is a revenue driver in the ophthalmologist office -- and they don't make it to the retina physician's office where they could get access to anti-VEGF therapy.

DME 持續成長帶來的挑戰是，許多患者從未到過視網膜專科醫師的診間。他們去看眼科醫生，接受雷射治療——雷射治療是眼科診所的收入來源——但他們沒能去視網膜醫生的診所接受抗 VEGF 治療。

This has been a focus for us. We are educating. We're trying to educate patients that if they do have DME, they ought to get themselves to a retinal specialist. But this is chipping away at a habit among the ophthalmologists and it's going to take some time. But we continue to see that the DME market does offer substantial growth opportunities for us in the future. And as Len mentioned earlier, if and when we get the diabetic retinopathy indication that would be a further driver.

這一直是我們的關注重點。我們正在進行教育。我們正在努力教育患者，如果他們患有糖尿病性黃斑水腫（DME），就應該去看視網膜專科醫生。但這正在逐漸改變眼科醫生的習慣，這需要一些時間。但我們仍然看到，DME 市場在未來為我們提供了巨大的成長機會。正如 Len 之前提到的，如果我們確診患有糖尿病視網膜病變，那將是一個更大的推動因素。

Our next question comes from John Scotti from Evercore ISI.

我們的下一個問題來自 Evercore ISI 的 John Scotti。

Hi, good morning. On EYLEA, I think you previously mentioned that you were seeing a bit of an increase in your gross to net. I was just wondering if you're still seeing that steady increase in the gross to net and potentially smaller erosion in net price. And, if so, what's the magnitude of that, and whether or not you see this trend as stabilizing or continuing into 2017.

您好，早安。關於 EYLEA，我想你之前提到過，你的毛利與淨利潤之比略有上升。我只是想知道你是否仍然看到毛利與淨利之間的穩定增長，以及淨價可能出現的較小下滑。如果屬實，那麼規模有多大？您認為這種趨勢會趨於穩定還是會延續到 2017 年？

I don't think there's been much sequential change at all in the gross to net. Its been flat sequentially in the last two quarters.

我認為毛利潤與淨利之間並沒有太大的變化。過去兩個季度環比持平。

Next we have Cory Kasimov from JPMorgan.

接下來是來自摩根大通的科里·卡西莫夫。

Good morning, guys. Thanks for taking my question. With the PDUFA date for monthly PRALUENT early next year, can you talk a little bit about the importance of extended dosing in this set? Clearly this is a payer-constrained market today. But what might monthly dosing mean a little bit down the road? And how do you think about even maybe longer-term dosing options potentially entering this market from competition at some point in the future? Thanks.

各位早安。謝謝您回答我的問題。PRALUENT 每月一次的 PDUFA 日期定於明年初，您能否談談該系列藥物中延長給藥時間的重要性？顯然，如今這是一個受支付方制約的市場。但從長遠來看，每月一次的給藥方式可能意味著什麼呢？那麼，您如何看待未來某個時候，競爭對手可能會推出更長期的給藥方案進入這個市場？謝謝。

Yes, I'm not convinced that the driver of this market is whether or not you have something every other week or every month, or what have you. I do believe that people will be driven by the LDL lowering, by the outcomes data that we hope will support the LDL hypothesis, continue to support it, and largely driven by payers. They've already demonstrated that they will not pay for convenience.

是的，我不認為這個市場的驅動力在於你是否每隔一周或每月都有一些東西出售，或者其他什麼。我相信，人們會受到降低低密度脂蛋白膽固醇的影響，會受到我們希望能夠支持低密度脂蛋白膽固醇假說的結果數據的影響，並會繼續支持該假說，而且很大程度上會受到支付方的影響。他們已經證明，他們不會為便利性買單。

If you look at the hepatitis C class, they put a much less convenient regimen up against a much more expensive regimen. So, I don't think convenience per se is going to drive the market. On the other hand, we like to come up with offerings that are as convenient as possible for patients.

如果你看看C型肝炎的治療方案，你會發現他們把一種不太方便的治療方案和一種更昂貴的治療方案放在一起比較。所以，我認為便利性本身並不會推動市場發展。另一方面，我們希望提供盡可能方便患者的服務。

And just to add to that, so far the patients who have received PRALUENT on a every two week basis have been happy with the dosing sequence. Convenience is not a big issue. But, as Len pointed out, we'd like to offer another dosing form for those patients who do want monthly convenience. But this is not an issue in the marketplace at the current time.

此外，目前每兩週接受一次 PRALUENT 治療的患者對這種給藥順序感到滿意。便利性並不是一個重要議題。但是，正如 Len 指出的那樣，我們希望為那些希望每月服用一次的便利患者提供另一種給藥方式。但就目前市場而言，這並不是一個問題。

Next we have Jim Birchenough from Wells Fargo.

接下來是來自富國銀行的吉姆·伯奇諾夫。

Hi, guys. Just a question on the co-formulated ANG-2 EYLEA product, and referencing the data for the PDGF program. Is there anything in the co-formulation of the two drugs that limits the efficacy of each individual components, whether it's viscosity, an ability to inject the full dose, the amount of protein you're giving to the back of the eye? I'm just trying to see if there's any learnings from the PDGF program that might inform how we should think about the co-formulation part of this for the ANG-2 product. Thanks.

嗨，大家好。關於 EYLEA 聯合配方產品 ANG-2，以及參考 PDGF 專案的數據，我有一個問題。這兩種藥物的聯合配方中是否存在任何限制每種單獨成分療效的因素，例如黏度、注射全劑量的能力、以及注射到眼後部的蛋白質含​​量？我只是想看看 PDGF 專案是否有任何經驗可以指導我們如何考慮 ANG-2 產品的共配方部分。謝謝。

We have no reason to think there's any issues whatsoever with that, or that would have contributed at all to the results. And the results, we believe, simply reflect the biology, or the lack of biology here, for the PDGF pathway.

我們沒有任何理由認為這其中存在任何問題，或會對結果產生任何影響。我們認為，這些結果僅僅反映了 PDGF 路徑的生物學特性，或者說，反映了該通路缺乏生物學特性。

Next we have Yatin Suneja from SunTrust.

接下來是SunTrust銀行的Yatin Suneja。

Hi, guys. Thank you for taking my question. A question on PRALUENT. Could you comment on the value-based contract? We know Amgen mentioned that they are entering into value-based contract for their PCSK9. Is that happening with you? How do you see that impacting the dynamics going forward? Thank you.

嗨，大家好。感謝您回答我的問題。關於 PRALUENT 的一個問題。您能否就基於價值的合約發表一下看法？我們知道安進公司曾表示，他們正在就其 PCSK9 藥物簽訂基於價值的合約。你也有這種情況嗎？您認為這將如何影響未來的發展趨勢？謝謝。

One thing I should mention is many plans do not have the ability at the present time to enter into these types of arrangements. So, it's going to be a rarity that a plan is able to implement value-based contracting. However, for those that can do it, we are working with those plans to establish a value-based contract, where appropriate.

需要指出的是，目前許多計劃尚不具備達成此類協議的能力。因此，能夠實施基於價值的合約的計劃將會非常罕見。但是，對於那些能夠做到這一點的人，我們正在與這些計劃合作，在適當的情況下建立基於價值的合約。

Next we have Biren Amin from Jefferies.

接下來是來自傑富瑞集團的比倫·阿明。

Yes, thanks, guys for taking my questions. How do you think payers will define moderate to severe for atopic dermatitis patients, because we hear that community derms don't typically follow easier score add scales but instead look at body surface area to determine severity of the disease.

是的，謝謝各位回答我的問題。您認為支付者將如何定義異位性皮膚炎患者的中度至重度病情？因為我們聽說社區皮膚科醫師通常不採用簡單的評分加法量表，而是透過觀察體表面積來確定疾病的嚴重程度。

I think it varies by geography. In Europe, EZ 75 or PASI 75 is the driver of definition of disease in psoriasis. And we anticipate that EZ 75 will be something we have to educate physicians on, and they are already preparing themselves for that.

我認為這因地理位置而異。在歐洲，EZ 75 或 PASI 75 是乾癬疾病定義的驅動因素。我們預計 EZ 75 將會是我們需要對醫生進行培訓的內容，而他們也已經在為此做準備了。

In the United States you're correct. EZ scores are not relevant to the physicians. And IGA scores are not specific enough. So we're working right now on plans with payers on how to better define the disease. George?

在美國，你的說法是正確的。EZ評分與醫生無關。而且IGA評分不夠具體。所以我們目前正在與支付方合作制定計劃，以更好地定義這種疾病。喬治？

We should just let you know that obviously in our studies, on average, the patients that we study had more than 50% of their body surface at baseline covered by this disease. And a quarter of the patients had 85% or more of their body covered with this disease. This just shows how severely these patients are. And it's not just that their skin is covered with this rash, but this is a weepy, itchy horrific rash that they just can't escape.

我們應該讓您知道，顯然在我們的研究中，平均而言，我們研究的患者在基線時，超過 50% 的體表面積都被這種疾病覆蓋。四分之一的患者身上 85% 或以上的皮膚都被這種疾病覆蓋。這足以說明這些患者的病情有多嚴重。而且不只是他們的皮膚上長滿了這種皮疹，而是一種會流淚、奇癢無比的可怕皮疹，他們根本無法擺脫。

And remarkably enough, as we said, despite the heavy burden of disease at baseline, almost 40% of these patients achieved a clear or almost clear status. Rarely in this business do you have a privilege to be involved in a story like this that can make such a difference in patients' lives. We've been lucky here at Regeneron that we've done this a couple times already. We think that DUPIXENT is really a once-in-a-lifetime story where you can really impact such an important disease so dramatically, have an average 70% improvement among all patients.

值得注意的是，正如我們所說，儘管基線時疾病負擔很重，但近 40% 的患者達到了清除或幾乎清除的狀態。在這個行業裡，你很少有機會參與這樣一個能夠對病人生活產生如此巨大影響的故事。我們Regeneron公司很幸運，已經做過幾次這樣的事了。我們認為 DUPIXENT 真的是千載難逢的奇蹟，它能對這種重要的疾病產生如此巨大的影響，使所有患者的平均改善率達到 70%。

And the thing that's also so stunning to us about dupilumab is that it looks like it might have the promise to do likewise in a host of related allergic diseases, including the overall asthma population where, there again, in the most uncontrolled severe population, once again, the results are very impressive from our first pivotal study. And we think the same may be the case in a host of other allergic settings.

令我們感到震驚的是，dupilumab 似乎有望在許多相關的過敏性疾病中發揮同樣的作用，包括對整個氣喘人群，尤其是在最不受控制的嚴重氣喘人群中，我們第一個關鍵性研究的結果再次令人印象深刻。我們認為，在其他許多過敏環境中，情況可能也是如此。

So, the short answer to your question is, unfortunately, there's a lot of patients who have more than 50% of their body surface covered. Those patients are certainly, by any category, considered severe patients. As Bob already told you, many of them have exhausted all other options. And we just hope that all the other ancillary things don't keep these important patients from getting access to this important game/life changing drug.

所以，對於你的問題，簡短的回答是，很遺憾，有很多患者的體表面積超過 50% 都被覆蓋了。無論從哪個角度來看，這些患者無疑都屬於重症患者。正如鮑勃已經告訴你的那樣，他們中的許多人已經用盡了所有其他方法。我們只希望其他所有相關因素不會阻礙這些重要的患者獲得這種改變生命的重要藥物。

I would just amplify a tiny bit on what George has said, which is that in contrasted to PRALUENT, where we knew with PRALUENT, of course, that we could lower cholesterol rather dramatically. But to most patients, unless they are highly involved in the details in the details of their care -- which some are but many to them, that isn't the end all, be all, something that they wake up every day wondering how to get their cholesterol down. Of course, if they've had a heart attack and everybody in their family does, then they do pay attention to that.

我只想稍微補充一下喬治所說的，那就是與 PRALUENT 相比，我們知道 PRALUENT 當然可以顯著降低膽固醇。但對大多數患者來說，除非他們非常關注治療的細節——雖然有些人確實如此，但對他們來說，細節太多了，否則治療並不是他們每天醒來都要思考如何降低膽固醇的全部意義所在。當然，如果他們自己得過心臟病，而且家裡所有人都得過心臟病，那麼他們肯定會特別注意這件事。

But then there was the pushback -- Well, you don't really know, do you, that it improves outcomes? We're just going on a hypothesis even though there's a great deal of data to certainly support that hypothesis. So, it's not a disease that people are clamoring to get treated, and it's not outcomes that are readily in hand.

但隨後出現了反對意見——嗯，你真的知道它能改善結果嗎？我們只是基於一個假設進行推測，儘管有大量數據可以佐證這個假設。所以，這不是人們爭相治療的疾病，也不是能夠輕易獲得治療結果的疾病。

Contrast that with PRALUENT, where these patients are desperate for treatment -- truly desperate for treatment. And we're not talking about the topical treatments that are available such as steroids, or that might become available when you're dealing with small areas of relatively to mild to moderate disease. We're talking about the kind of patients George referred to, which are really quite significant.

與 PRALUENT 相比，這些患者非常渴望治療——真的非常渴望治療。我們說的還不是像類固醇這樣的局部治療方法，也不是在處理小面積的、相對較輕或中度的疾病時可能出現的治療方法。我們說的是喬治提到的那類病人，他們非常重要。

And these patients can see the outcome themselves. They can tell that they are doing better. And we see it in our studies, we see it in our questionnaires, we see it in whether or not they are sleeping because they can scratch themselves so badly.

而這些患者可以親眼看到治療結果。他們能感覺到自己情況好轉了。我們在研究中看到了這一點，在問卷調查中看到了這一點，從他們是否能睡個好覺就能看出這一點，因為他們會因為抓撓自己而感到非常難受。

I heard a story the other day, it was a group of us, which practically brought us all to tears, where a little boy was visiting his grandparents and cuddling and sleeping on the same bed with very bad atopic dermatitis, said to his grandparents -- can you each hold one of my hands when I sleep so I don't scratch myself so badly. Think about that.

前幾天我們一群人聽到一個故事，幾乎把我們都感動得流淚了。故事講的是一個小男孩去看他的祖父母，他患有非常嚴重的異位性皮膚炎，和祖父母依偎在一起睡在同一張床上。小男孩對祖父母說：“我睡覺的時候，你們能不能一人握住我的一隻手，這樣我就不會抓撓得那麼厲害了？”想想看。

This is a disease that people really are looking for treatments. And if we can get this drug approved, first for adults and hopefully down the road for children, we can really provide something that they can tangibly feel. We're passionate about making is sure that we remove all the barriers out there. And we expect to work with patients, with doctors, with payers, with organizations to make sure that people are aware of this treatment and can get access to it.

人們確實在尋求這種疾病的治療方法。如果我們能夠獲得這種藥物的批准，首先用於成人，希望將來也能用於兒童，我們就能真正為他們提供一些他們能夠切實感受到的東西。我們熱衷於確保消除所有障礙。我們希望與患者、醫生、支付者和組織合作，確保人們了解這種治療方法並能夠獲得這種治療方法。

Our final question comes from Phil Nadeau from Cowen and Company.

最後一個問題來自 Cowen and Company 的 Phil Nadeau。

Good morning. Thanks for fitting me in. Just one question on some of your prepared remarks. You mentioned that your competition for EYLEA is beginning to increase the discounts that they are offering. I want to understand the dynamics there a bit more. Is there a set cycle for when discounts are negotiated? And are there any signs that you're seeing that this is something that's demanded by payers? Or is this something that the competition has taken it upon themselves to do?

早安.謝謝你安排我過來。關於您事先準備好的發言稿，我只有一個問題。您提到，EYLEA 的競爭對手開始加強折扣。我想更深入地了解那裡的運作機制。折扣談判是否有固定的週期？是否有任何跡象表明這是付款方所要求的？還是這是競爭對手自行採取的行動？

Remember, this is a Part B drug. And it's really not the same kind of environment where you have a timing and a cycle with patients. There's some small amount of that that goes on, but for the most part the discounts and rebates that have been offered have been directly back to the physicians' offices, et cetera.

請記住，這是B類藥物。而且，這與你在診療過程中需要掌握時機和安排​​治療週期的環境截然不同。雖然確實存在少量此類情況，但大部分的折扣和回扣都是直接退還給醫生辦公室等機構。

We continually reevaluate that situation. We look at what the impact. We're very sensitive to doctors not have to make a choice of what to give their patients what they might think the best drug would be because of a rebate situation or something like that. We think most retinal physicians don't do that, but we certainly understand the real world and as the market shifts we're prepared to react, if necessary.

我們會持續重新評估這種情況。我們來看看會產生什麼影響。我們非常理解醫生不應該因為回扣或其他類似原因，而被迫在給病人使用他們認為最好的藥物之間做出選擇。我們認為大多數視網膜醫生不會這樣做，但我們當然了解現實世界，隨著市場的變化，我們已做好準備，在必要時做出反應。

Great. Thank you all for joining the call today. As we mentioned before, the IR team and Bob, the Chief Financial Officer, will be available to answer any questions that didn't make it on the call. That ends the call for today.

偉大的。感謝各位今天參加電話會議。正如我們之前提到的，投資者關係團隊和財務長鮑伯將隨時解答電話會議上沒有提到的任何問題。今天的通話就到此結束了。

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。