雷傑納榮製藥 (REGN) 2017 Q3 法說會逐字稿

Welcome to the Regeneron Pharmaceuticals Q3 2017 Earnings Conference Call. My name is Paulette, and I will be your operator for today's call. (Operator Instructions) Please note that this conference is being recorded.

歡迎參加 Regeneron Pharmaceuticals 2017 年第三季財報電話會議。我叫寶萊特，我將擔任您今天通話的接線生。（操作員說明）請注意，本次會議正在錄音。

I will now turn the call over to Manisha Narasimhan, Head of Regeneron's Investor Relations. You may begin.

現在我將把電話轉交給 Regeneron 投資者關係主管 Manisha Narasimhan。你可以開始了。

Thank you, Paulette. Good morning, and welcome to Regeneron Pharmaceuticals' Third Quarter 2017 Conference Call. An archive of this webcast will be available on our website under events for 30 days. Joining me on the call today are Dr. Leonard Schleifer, Founder, President and CEO; Dr. George Yancopoulos, Founding Scientist, President and Chief Scientific Officer; Bob Terifay, Executive Vice President, Commercial; and Bob Landry, Chief Financial Officer. After prepared remarks, we will open the call for Q&A.

謝謝你，寶萊特。早安，歡迎參加 Regeneron Pharmaceuticals 2017 年第三季電話會議。本次網路直播的存檔將在我們網站的「活動」欄位下保留 30 天。今天與我一起參加電話會議的有：創辦人、總裁兼執行長 Leonard Schleifer 博士；創始科學家、總裁兼首席科學官 George Yancopoulos 博士；商業執行副總裁 Bob Terifay；以及財務長 Bob Landry。在發言結束後，我們將開放問答環節。

I would also like to remind you that remarks made on this call today include forward-looking statements about Regeneron. Such statements may include, but are not limited to those related to Regeneron and its products and business, sales and expense forecasts, financial forecasts, development programs and related anticipated milestones, collaborations, finances, regulatory matters, intellectual property, pending litigation 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 that statement. 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, 2017, which was filed with the SEC this morning.

我還要提醒各位，今天電話會議上發表的言論包含 Regeneron 的前瞻性陳述。此類聲明可能包括但不限於與 Regeneron 及其產品和業務、銷售和支出預測、財務預測、開發計劃和相關預期里程碑、合作、財務、監管事項、智慧財產權、未決訴訟和競爭相關的聲明。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該聲明中預測的結果和事件有重大差異。有關這些及其他重大風險的更完整描述，請參閱 Regeneron 向美國證券交易委員會 (SEC) 提交的文件，包括其截至 2017 年 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 does not undertake any obligation to update publicly any forward-looking statement, whether as a result of new information, future events or otherwise. 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 those measures to GAAP is available in our financial results press release, which can be accessed on our website at www.regeneron.com. Once our call concludes, Bob Landry and the IR team will be available to answer further questions.

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。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以及這些指標與公認會計準則的調節表的信息，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。通話結束後，鮑伯·蘭德里和投資者關係團隊將回答進一步的問題。

With that, let me turn the call over to our President and Chief Executive Officer, Dr. Len Schleifer.

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, Manisha, and a very good morning to everyone who has joined us on the call and webcast today. In my remarks, I'd like to focus on to EYLEA and Dupixent, which are 2 important near-term drivers of our business and also cover some of our late-stage pipeline progress.

謝謝瑪妮莎，也祝今天所有參加電話會議和網路直播的朋友們早安。在我的演講中，我想重點談談 EYLEA 和 Dupixent，它們是我們業務近期兩個重要的驅動因素，也涵蓋了我們一些後期研發管線的進展。

EYLEA is a very important franchise to Regeneron and has continued to perform strongly in the third quarter, with 12% year-over-year growth in the U.S. and 20% year-over-year growth outside the United States. We are committed to maintaining our leadership in retinal diseases.

EYLEA 是 Regeneron 非常重要的特許經營品牌，在第三季度繼續保持強勁的業績，在美國同比增長 12%，在美國以外地區同比增長 20%。我們致力於維持在視網膜疾病領域的領先地位。

Today, I want to talk specifically about our long-term strategy to drive EYLEA growth. Our EYLEA sales are primarily derived from 2 large and distinct vision-threatening retinal diseases, age-related macular degeneration also known as wet AMD and diabetic macular edema, or DME.

今天，我想重點談談我們推動安永成長的長期策略。我們的EYLEA銷售額主要來自兩種大型且不同的威脅視力的視網膜疾病：老年黃斑部病變（也稱為濕性AMD）和糖尿病黃斑水腫（DME）。

Wet AMD represents approximately 70% of our U.S. EYLEA net sales and continues to grow as the population ages. There are approximately 1 million patients with wet AMD in the United States and about 60% of them received anti-VEGF therapy. Our goal in wet AMD is to ensure that patients are optimally treated to achieve the best visual outcomes and as importantly, maintain these vision gains over the long term using regular treatment in accordance with the labeled indication.

濕性老年黃斑部病變約占我們美國EYLEA淨銷售額的70%，且隨著人口老化，這一比例持續增加。美國約有 100 萬名濕性 AMD 患者，其中約 60% 的患者接受了抗 VEGF 治療。我們在濕性 AMD 治療中的目標是確保患者得到最佳治療，從而獲得最佳的視覺效果，更重要的是，透過按照適應症進行定期治療，長期維持這些視力改善。

Our DME business represents approximately 25% of our U.S. EYLEA net sales and has been growing steadily. We expect it to be an important driver of future growth. EYLEA is currently the branded anti-VEGF market leader in diabetic macular edema. This position was strengthened by data from Protocol T, which was an NIH-sponsored comparative effectiveness study in which diabetic macular edema that demonstrate -- and demonstrated that EYLEA treatment resulted in significantly greater gains in visual acuity than both Lucentis and Avastin treatment as well as significantly greater control of the edema itself.

我們的DME業務約佔安永美國淨銷售額的25%，並且一直在穩步成長。我們預計它將成為未來成長的重要驅動力。EYLEA目前是糖尿病性黃斑水腫領域抗VEGF藥物的市場領導者。Protocol T 的數據強化了這一立場。 Protocol T 是一項由美國國立衛生研究院 (NIH) 資助的比較效果研究，該研究針對糖尿病性黃斑水腫，結果表明，與 Lucentis 和 Avastin 治療相比，EYLEA 治療在提高視力方面效果顯著，並且在控制水腫方面效果也顯著更佳。

The current treatment rates in diabetic eye diseases remain low. In DME, the majority of patients are either untreated or received laser therapy, which in our pivotal trials was shown to be substantially inferior to treatment with EYLEA.

目前糖尿病眼疾的治療率仍然很低。在 DME 中，大多數患者要么未接受治療，要么接受了雷射治療，而我們的關鍵性試驗表明，雷射治療的效果遠不如 EYLEA 治療。

From a market penetration perspective, it's estimated that only about 10% of patients with DME in the United States are currently treated with an anti-VEGF agent. Thus, DME represents a significant growth opportunity for EYLEA.

從市場滲透率的角度來看，據估計，目前美國祇有約 10% 的 DME 患者接受抗 VEGF 藥物治療。因此，DME 代表著安永的重要成長機會。

From a competitive perspective, we are not aware of any near-term, late-stage competitive threats on the horizon in DME. It is important to remember that DME represents only a part of the overall diabetic eye disease opportunity for anti-VEGF therapy, which includes both proliferative and non-proliferative diabetic retinopathy without diabetic macular edema. Recent data from a third-party study comparing EYLEA with pan-retinal laser photocoagulation in patients with proliferative diabetic retinopathy demonstrated that with EYLEA -- the resulted improvement in visual outcomes at -- EYLEA resulted in improved visual outcomes at the end of one year. These data from the clarity study were published in Lancet in May of this year. George will review these important results in greater detail. As a reminder, EYLEA is approved in diabetic retinopathy for patients with DME.

從競爭角度來看，我們目前還沒有發現DME領域在近期或後期出現任何競爭威脅。需要注意的是，DME 只是抗 VEGF 療法治療糖尿病眼部疾病整體機會的一部分，該療法還包括增殖性和非增殖性糖尿病視網膜病變，但不包括糖尿病黃斑水腫。最近一項第三方研究的數據比較了 EYLEA 與全視網膜雷射光凝術在增殖性糖尿病視網膜病變患者中的療效，結果表明，EYLEA 在一年後能改善視力結果。這項來自 Clarity 研究的數據已於今年 5 月發表在《柳葉刀》雜誌上。喬治將更詳細地審查這些重要結果。再次提醒，EYLEA 已獲準用於治療糖尿病視網膜病變和糖尿病黃斑水腫 (DME) 患者。

It's estimated that there are approximately 500,000 patients in the United States with proliferative diabetic retinopathy and a vast majority are currently treated with laser therapy because of perceived medical urgency. Data from the clarity study could potentially support the use of EYLEA in this setting.

據估計，美國約有 50 萬名患有增殖性糖尿病視網膜病變的患者，由於人們認為治療具有緊迫性，絕大多數患者目前都接受雷射治療。清晰度研究的數據可能支持在這種環境下使用 EYLEA。

In the U.S, there are approximately 1.8 million patients with vision-threatening diabetic retinopathy, including DME, proliferative diabetic retinopathy and severe non-proliferative diabetic retinopathy.

在美國，大約有 180 萬名患有威脅視力的糖尿病視網膜病變的患者，其中包括糖尿病黃斑水腫、增殖性糖尿病視網膜病變和嚴重的非增殖性糖尿病視網膜病變。

Currently, fewer than 30% of these patients are treated with anti-VEGF agents, representing a substantial potential market opportunity for EYLEA in diabetic eye diseases.

目前，只有不到 30% 的糖尿病眼疾患者接受了抗 VEGF 藥物治療，這為 EYLEA 在糖尿病眼部疾病領域提供了巨大的潛在市場機會。

We have completed enrollment in our Phase III PANORAMA study of EYLEA compared to sham therapy in patients with non-proliferative diabetic retinopathy without DME and expect top line data in the first half of 2018. George will review the strong data available that bode well for the PANORAMA study.

我們已經完成了 EYLEA 與安慰劑治療在非增殖性糖尿病視網膜病變（無 DME）患者中的 III 期 PANORAMA 研究的入組，預計將在 2018 年上半年獲得初步數據。喬治將審查現有強有力的數據，這些數據預示著 PANORAMA 研究將會取得良好結果。

We are actively pursuing the indication of diabetic retinopathy and plan to submit a supplemental BLA in the second half of 2018 for this indication based on the PANORAMA study, should it be positive.

我們正在積極尋求糖尿病視網膜病變的適應症，並計劃在 2018 年下半年根據 PANORAMA 研究的結果，提交補充生物製品許可申請 (BLA)，前提是該研究結果為陽性。

In addition to our PANORAMA study, the diabetic retinopathy clinical research network is conducting an government-sponsored Phase III study of EYLEA known as Protocol-W in diabetic retinopathy.

除了我們的 PANORAMA 研究之外，糖尿病視網膜病變臨床研究網絡正在進行一項政府資助的 EYLEA III 期研究，該研究被稱為糖尿病視網膜病變 Protocol-W。

Let's turn now to Dupixent. The launch in atopic dermatitis is underway and progressing very well. Right from the early stages of the launch and continuing to the present, we have had a steady stream of about 500 prescriptions filled weekly for patients who are new to the brand. Our patient and physician satisfaction rates are high, with over 90% of patients refilling their Dupixent prescription.

現在我們來看看Dupixent。針對異位性皮膚炎的上市工作正在進行中，進展非常順利。從產品上市初期到現在，我們每週都有大約 500 張處方被新患者使用。我們的患者和醫生滿意度都很高，超過 90% 的患者會再次購買 Dupixent 處方藥。

We have completed our Phase III program of dupilumab in asthma, and we and Sanofi are working toward a planned supplemental BLA submission to the FDA by the end of this year.

我們已經完成了度普利尤單抗治療氣喘的 III 期臨床試驗項目，我們和賽諾菲正在努力爭取在今年年底前向 FDA 提交補充生物製品許可申請。

We recognized it will be a very competitive area and are confident that the efficacy and safety profile of dupilumab will place it in a very strong position if approved in asthma. The dupilumab pivotal asthma program was the first with a biologic to enroll a broad population of uncontrolled asthma patients and demonstrate large and significant reductions in exacerbations and clinically significant improvements in lung function.

我們意識到這將是一個競爭非常激烈的領域，並相信如果 dupilumab 獲準用於治療氣喘，其療效和安全性將使其處於非常有利的地位。dupilumab 關鍵性氣喘計畫是第一個使用生物製劑招募大量未控制氣喘患者，並證明可大幅顯著減少氣喘急性發作和顯著改善肺功能的臨床計畫。

In terms of our broad strategy, we believe that dupilumab has the potential to improve the lives of patients with other allergic diseases because it targets a common central driver of type 2 inflammation.

從我們的整體策略來看，我們相信度普利尤單抗有潛力改善其他過敏性疾病患者的生活，因為它針對的是 2 型發炎的常見中心驅動因素。

In addition to atopic dermatitis and asthma, we have completed enrollment in 2 Phase III studies in nasal polyps and recently reported Phase II data in eosinophilic esophagitis, a disease with no FDA-approved treatment.

除了異位性皮膚炎和氣喘之外，我們還完成了 2 項鼻息肉 III 期研究的入組，並且最近公佈了嗜酸性食道炎的 II 期數據，這種疾病目前尚無 FDA 批准的治療方法。

We believe this broad activity across these multiple allergic diseases is unique among the biologic therapy. George will update you further on dupilumab data and clinical progress, and Bob Terifay will update you on our commercial activity.

我們認為這種針對多種過敏性疾病的廣泛活性在生物療法中是獨一無二的。George 將向您進一步介紹 dupilumab 的數據和臨床進展，Bob Terifay 將向您介紹我們的商業活動。

With regard to our PCSK9 antibody Praluent, we believe that there is substantial opportunity yet to be realized. We await data from our ODYSSEY OUTCOMES study in the first quarter of next year, and we continue to work on access, which is slowly starting to improve for this class of therapy. We are pleased with the recent appellate court decision in our ongoing litigation concerning Praluent, which vacated the injunction and referred the case back for retrial in the District Court.

關於我們的 PCSK9 抗體 Praluent，我們認為還有巨大的發展機會尚未實現。我們正在等待 ODYSSEY OUTCOMES 研究在明年第一季的數據，並且我們將繼續努力改善此類療法的可及性，目前該療法的可及性正在緩慢改善。我們對上訴法院最近就我們正在進行的關於 Praluent 的訴訟作出的裁決感到滿意，該裁決撤銷了禁令，並將案件發回地方法院重審。

The appellate court ruled that the law requires a written description of the invention. In this case, the antibodies, not the antigen or epitope they bind to. Moreover, they instructed the district court to admit important new evidence that was improperly excluded from the first trial.

上訴法院裁定，法律要求對發明進行書面描述。在這種情況下，指的是抗體，而不是它們結合的抗原或抗原決定基。此外，他們也指示地方法院採納第一次審判中被不當排除的重要新證據。

Finally, our immuno-oncology program with cemiplimab, our PD-1 antibody, continues to advance. We are moving forward with the first planned regulatory submission in advanced cutaneous squamous cell carcinoma, a difficult to treat skin cancer as well as expanding the development program in first and second-line lung cancer, basal cell carcinoma and cervical cancer in addition to studies in combination with other antibodies and bispecifics.

最後，我們採用 PD-1 抗體 cemiplimab 所進行的免疫腫瘤學計畫正在進行中。我們正在推進針對晚期皮膚鱗狀細胞癌（一種難以治療的皮膚癌）的首個計劃監管申請，同時擴大一線​​和二線肺癌、基底細胞癌和子宮頸癌的開發計劃，並開展與其他抗體和雙特異性抗體聯合治療的研究。

Our pipeline continues to be robust with 16 product candidates in clinical development, all of which were discovered in our own labs and serve as a testament to the fact that our innovation engine continues to be exceedingly strong and productive.

我們的研發管線依然強勁，目前有 16 個候選產品正在進行臨床開發，所有這些產品都是在我們自己的實驗室中發現的，證明了我們的創新引擎仍然非常強大且高效。

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

接下來，我想把電話交給喬治。

Thank you, Len, and a very good morning to everyone who has joined us on the call. As Len mentioned, EYLEA continues to be a leader in the retinal disease space with a number of important near-term opportunities.

謝謝Len，也祝所有參加電話會議的朋友們早安。正如 Len 所提到的，EYLEA 仍然是視網膜疾病領域的領導者，並且有許多重要的近期機會。

First, we expect to have our supplemental BLA for every 12-week dosing of EYLEA in wet AMD filed by the end of this year. Echoing Len's thoughts, let me also update you on the potential opportunity for EYLEA in diabetic eye disease.

首先，我們預計在今年年底前提交針對濕性 AMD 的 EYLEA 每 12 週給藥方案的補充 BLA 申請。我同意 Len 的想法，也想向大家介紹一下 EYLEA 在糖尿病眼部疾病治療的潛在機會。

In our original pivotal studies in DME, we demonstrated superiority of EYLEA to laser in terms of visual acuity and other outcomes. In the government-sponsored Protocol-T study, EYLEA was demonstrated to be superior in terms of visual acuity to the other commonly used anti-VEGF agents at the 1-year primary endpoint.

在我們最初針對 DME 的關鍵研究中，我們證明了 EYLEA 在視力和其他結果方面優於雷射。在政府資助的 Protocol-T 研究中，EYLEA 在 1 年主要終點時，視力方面被證明優於其他常用的抗 VEGF 藥物。

In these studies, in addition to these endpoints, EYLEA demonstrated a 2 or more step improvement in the diabetic retinopathy severity score, or DRSS, suggesting activity in both proliferative and non-proliferative diabetic retinopathy.

在這些研究中，除了這些終點之外，EYLEA 還表現出糖尿病視網膜病變嚴重程度評分 (DRSS) 改善 2 級或更多級，顯示其對增殖性和非增殖性糖尿病視網膜病變均有效。

Consistent with this, as Len mentioned, positive data from the third-party clarity study in patients with proliferative diabetic retinopathy were recently published in the Lancet. The medical urgency in this setting is reflected by the fact that the vast majority of proliferative patients are currently treated with pan-retinal photocoagulation laser therapy, or PRP, which has been the standard of care in this indication for almost 4 decades.

與此一致的是，正如 Len 所提到的，第三方 Clarity 研究對增殖性糖尿病視網膜病變患者的積極數據最近發表在《柳葉刀》上。在這種情況下，醫療的迫切性體現在絕大多數增生性視網膜病變患者目前接受的是全視網膜光凝固雷射療法（PRP），而 PRP 已成為此適應症近 40 年的標準治療方法。

Clarity compared EYLEA to PRP and showed that patients treated with EYLEA gained approximately 4 letters in visual acuity compared to patients treated with laser.

Clarity 將 EYLEA 與 PRP 進行了比較，結果表明，與接受雷射治療的患者相比，接受 EYLEA 治療的患者視力提高了約 4 個字母。

This was the first time that an anti-VEGF agent has demonstrated superiority to laser treatment in patients with diabetic retinopathy without macular edema. According to this published study, compared to PRP, EYLEA lowered the rate of new or increasing vitreous hemorrhage by about 50% and decreased the occurrence of macular edema at 52 weeks by approximately 60%.

這是抗 VEGF 藥物首次在治療無黃斑水腫的糖尿病視網膜病變患者中證明優於雷射治療。根據這項已發表的研究，與 PRP 相比，EYLEA 使新發或加重的玻璃體出血率降低了約 50%，並在 52 週時使黃斑水腫的發生率降低了約 60%。

In addition, an improvement in retinopathy from proliferative to non-proliferative was observed in 64% of patients treated with EYLEA compared to 34% of patients treated with the PRP.

此外，接受 EYLEA 治療的患者中有 64% 的視網膜病變從增殖性改善為非增殖性，而接受 PRP 治療的患者中只有 34% 的視網膜病變從增殖性改善為非增殖性。

There were no new safety concerns observed with EYLEA in this study. Inflammation was more frequent in patients who received EYLEA, with 8% of patients supporting inflammation compared to 3% of patients who received PRP.

本研究中未發現 EYLEA 有新的安全性問題。接受 EYLEA 治療的患者中炎症發生率較高，8% 的患者出現炎症，而接受 PRP 治療的患者中炎症發生率為 3%。

Near increasing vitreous hemorrhage was more frequent in the PRP group, with 18% of patients supporting this event compared to 9% in the EYLEA group.

PRP 組中玻璃體出血逐漸加重的發生率較高，18% 的患者出現這種情況，而 EYLEA 組則為 9%。

PANORAMA, our Phase III study of EYLEA in patients with non-proliferative diabetic retinopathy without diabetic macular edema, exploring every 8 and 16-week dosing is fully enrolled.

PANORAMA 是我們正在進行的 EYLEA 對非增殖性糖尿病視網膜病變（無糖尿病黃斑水腫）患者的 III 期研究，探索每 8 週和 16 週給藥一次的效果，目前已完成全部受試者招募。

We expect to report data in the first half of 2018 and if positive, expect to make a regulatory submission. A separate Phase III study in this indication, Protocol-W, which is being conducted by the diabetic retinopathy clinical research network, or the DRCR, continues to enroll patients. This study will explore every 16-week dosing of EYLEA, which is the only anti-VEGF treatment being investigated in this study.

我們預計將於 2018 年上半年公佈數據，如果結果積極，預計將向監管機構提交申請。另一項針對此適應症的 III 期研究（Protocol-W）由糖尿病視網膜病變臨床研究網絡（DRCR）進行，目前仍在招募患者。本研究將探討每 16 週一次的 EYLEA 給藥方案，EYLEA 是本研究中唯一正在研究的抗 VEGF 治療方法。

Finally, on EYLEA, I want to remind you that we expect to have the top line data from our Phase II combination studies of EYLEA and nesvacumab, our antibody to ang-2 later this quarter.

最後，關於 EYLEA，我想提醒大家，我們預計將在本季度晚些時候獲得 EYLEA 和 nesvacumab（我們的抗 ang-2 抗體）的 II 期聯合研究的主要數據。

While we have not seen the data, we have been pretty clear about the high bar that EYLEA monotherapy sets for any potential combination studies. In our view, the results from the ang-2 combination studies are not central to the eye disease strategy that we have just outlined.

雖然我們還沒有看到相關數據，但我們已經非常明確地指出，EYLEA 單藥療法為任何潛在的聯合療法研究設定了很高的標準。我們認為，Ang-2 聯合研究的結果與我們剛才概述的眼部疾病治療策略並不密切相關。

Turning now to dupilumab. Our IL-4/13 blocker that is currently approved for the treatment of moderate to severe atopic dermatitis in adult patients whose disease is not adequately controlled with topical prescription therapies or when therapies -- those therapies are not advisable.

接下來我們來看看度普利尤單抗。我們目前獲準用於治療中度至重度異位性皮膚炎的成人患者，這些患者的病情無法透過局部處方療法得到充分控制，或不建議使用這些療法。

We recently reported positive Phase III results from 2 studies with dupilumab in patients with uncontrolled asthma, LIBERTY ASTHMA QUEST and LIBERTY ASTHMA VENTURE. These 2 studies, in addition to our first pivotal study, enrolled a broad population of uncontrolled asthma patients and demonstrated reductions in exacerbations or asthma attacks and improvements in lung function as measured by FEV1.

我們最近發表了兩項針對未控制氣喘患者的 dupilumab 研究的正面 III 期結果，分別是 LIBERTY ASTHMA QUEST 和 LIBERTY ASTHMA VENTURE。除了我們先前的關鍵性研究之外，這兩項研究還納入了大量未控制的氣喘患者，結果表明，氣喘急性發作或氣喘發作次數減少，肺功能（以 FEV1 衡量）得到改善。

The VENTURE study, which enrolled patients who required chronic systemic corticosteroids for asthma control showed that dupilumab could profoundly reduce systemic corticosteroid dependence with half the patients eliminating this dependence entirely. Despite the reduction in systemic corticosteroid usage, dupilumab treated patients still had prominent increases in lung functions and fewer exacerbations compared to the control group. Based on these data, dupilumab offers the potential for an important treatment alternative to systemic corticosteroids for these most serious of asthma patients.

VENTURE 研究招募了需要長期使用全身性皮質類固醇來控制氣喘的患者，結果表明，度普利尤單抗可以顯著降低全身性皮質類固醇的依賴性，其中一半患者完全擺脫了這種依賴性。儘管全身性皮質類固醇的使用量減少了，但與對照組相比，接受度普利尤單抗治療的患者肺功能仍有顯著提高，病情加重次數也更少。根據這些數據，度普利尤單抗有望成為治療這些最嚴重的氣喘患者的重要替代全身性皮質類固醇的治療方案。

Beyond the profound benefit in terms of exacerbations, I would like to emphasize the importance of dupilumab's demonstrated ability to improve lung function in asthma patients. Since currently approved biologics do not consistently improve lung functions and were approved based on their ability to reduce exacerbations, this has resulted in a focus away from lung function in asthma.

除了在緩解病情加重方面帶來的顯著益處外，我還想強調度普利尤單抗在改善氣喘患者肺功能方面所展現出的能力的重要性。由於目前核准的生物製劑並不能持續改善肺功能，而且當初獲批是基於其減少氣喘急性發作的能力，因此，人們的關注點逐漸從氣喘的肺功能轉移開來。

However, one of the most serious day-to-day issues that patients with uncontrolled asthma suffer from and which dramatically impacts their lives is their inability to breathe normally.

然而，對於未控制氣喘的患者來說，日常生活中最嚴重的問題之一，也是對他們生活造成極大影響的問題，就是無法正常呼吸。

For example, the patients in our pivotal studies only retained an average of 50% to 60% of a predicted FEV1 at baseline despite treatment with steroids and long-acting beta agonist. Moreover, only a fraction of this lung function could be reversed with high doses of short-acting bronchodilators. Therefore, we believe our finding that dupilumab improved lung function in all of our clinical trials in addition to reducing exacerbations is an important potential benefit to patients, if approved in this setting.

例如，在我們關鍵的研究中，儘管接受了類固醇和長效β受體激動劑治療，患者在基線時僅保留了預測FEV1的50%至60%。此外，即使使用高劑量短效支氣管擴張劑，也只能逆轉部分肺功能。因此，我們認為，如果 dupilumab 在此領域獲得批准，那麼在我們所有的臨床試驗中，除了減少病情加重外，還能改善肺功能，這項發現對患者來說將是一個重要的潛在益處。

Results from the QUEST and VENTURE studies along with data from our previously reported and published with pivotal Phase IIb study will support the regulatory submission that we and Sanofi expect to make to the FDA by the end of this year.

QUEST 和 VENTURE 研究的結果，以及我們先前報告和發表的關鍵性 IIb 期研究的數據，將支持我們和賽諾菲預計將在今年年底前向 FDA 提交的監管申請。

As a reminder, the recently reported QUEST and VENTURE studies included adolescent patients between the ages of 12 and 17 years. We're also currently conducting a Phase III study in pediatric patients between the ages of 6 and 11 years.

提醒一下，最近報道的 QUEST 和 VENTURE 研究納入了 12 至 17 歲的青少年患者。我們目前也正在對 6 至 11 歲的兒科患者進行 III 期研究。

Work on the development of dupilumab and other type 2 diseases such as nasal polyposis and eosinophilic esophagitis is ongoing. Following positive results in Phase II, I'm pleased to report that both Phase III studies in patients with nasal polyposis are now fully enrolled.

針對度普利尤單抗和其他 2 型疾病（如鼻息肉和嗜酸性食道炎）的研發工作正在進行中。在 II 期臨床試驗取得正面成果後，我很高興地宣布，目前針對鼻息肉患者的兩項 III 期臨床試驗均已完成患者招募。

Turning to eosinophilic esophagitis, or EOE, a chronic type 2 immune-mediated disease that is strongly associated with food allergies. EOE is characterized by pain and difficulty swallowing, and the possibility of food impaction, which are consequences of pathological structural changes in the esophagus.

接下來我們來談談嗜酸性食道炎（EOE），這是一種慢性 2 型免疫介導疾病，與食物過敏有密切關係。嗜酸性食道炎 (EOE) 的特徵是疼痛和吞嚥困難，以及食物嵌塞的可能性，這些都是食道病理結構變化的結果。

There are currently no approved therapies in the U.S. for the treatment of EOE. All corticosteroids are used off label, but with limited long-term efficacy and safety data to support their use. At the recent World Congress of Gastroenterology, we presented additional data from our positive Phase II study. These data show that dupilumab significantly improved swallowing, in addition to esophageal eosinophil counts, endoscopic features histology and esophageal distensibility in adults with active EOE compared with placebo. This safety profile seen in the study was consistent with that observed in the other studies of dupilumab.

目前美國尚無核准的治療嗜酸性粒細胞性食道炎（EOE）的療法。所有皮質類固醇均屬於超適應症用藥，但缺乏長期療效和安全性數據來支持其使用。在最近舉行的世界胃腸病學大會上，我們展示了我們積極的 II 期研究的更多數據。這些數據表明，與安慰劑相比，度普利尤單抗顯著改善了活動性嗜酸性粒細胞性食道炎 (EOE) 成年患者的吞嚥功能，以及食道嗜酸性粒細胞計數、內視鏡特徵組織學和食道擴張性。研究中觀察到的安全性特徵與其他度普利尤單抗研究中觀察到的安全性特徵一致。

Dupilumab has been granted orphan drug designation in this indication, and Phase III studies are being planned.

Dupilumab 已獲得此適應症的孤兒藥資格認定，目前正在計劃進行 III 期臨床試驗。

I'd like to now turn to atopic dermatitis, an indication where Dupixent is approved both in the United States and in Europe. In September, we presented positive data from CAFÉ, a Phase III study of Dupixent in patients with moderate to severe atopic dermatitis who are inadequately controlled with or intolerant of cyclosporine, which is approved in certain countries outside the United States. This study demonstrated that these -- in these difficult to treat patients, Dupixent in combination with topical steroids significantly improved measures of overall disease severity and patient-reported quality of life measures, with the mean improvement of 80% in the eczema area and severity score or the easy score. No new adverse events were reported in this study. We're also continuing to work on expanding development in moderate to severe pediatric atopic dermatitis patients.

現在我想談談異位性皮膚炎，Dupixent 在美國和歐洲都已獲準用於治療疾病。9 月，我們公佈了 CAFÉ 的積極數據，這是一項針對中重度異位性皮膚炎患者的 Dupixent III 期研究，這些患者對環孢素（在美國以外的某些國家已獲批准）的控制不佳或不耐受。這項研究表明，對於這些難以治療的患者，Dupixent 與局部類固醇聯合使用可顯著改善疾病總體嚴重程度和患者報告的生活品質指標，濕疹面積和嚴重程度評分或易感評分平均改善 80%。本研究中未報告新的不良事件。我們也持續努力擴大針對中度至重度兒童異位性皮膚炎患者的研發工作。

Turning to immuno-oncology, which is another area of growing excitement for us. I'd like to begin with cemiplimab, our foundational PD-1 antibody. Our lead indication is advanced cutaneous squamous cell carcinoma, or CSCC, for which we have been granted breakthrough designation by the FDA. We expect to report interim data later this year and to make a regulatory submission to the FDA in the first quarter of 2018.

接下來是免疫腫瘤學，這是我們越來越感興趣的另一個領域。我想先從cemiplimab說起，這是我們的基礎性PD-1抗體。我們的主要適應症是晚期皮膚鱗狀細胞癌（CSCC），我們已獲得美國食品藥物管理局（FDA）授予的突破性療法認定。我們預計今年稍後公佈中期數據，並於 2018 年第一季向 FDA 提交監管申請。

Our PD-1 program has continued to expand. We recently initiated a Phase III program of cemiplimab monotherapy in first-line non-small cell lung cancer. This 300-patient study, which is being conducted outside the United States, will enroll patients who express greater than 50% PD-L1 and will compare cemiplimab to standard of care platinum doublet. The primary endpoint of this study is progression-free survival. We're planning additional studies, including combinational studies in non-small cell lung cancer as well as clinical trials in the second-line non-small cell lung cancer. Remind you that with all the recent failures in this space, there is only one approved PD-1 or PD-L1 agent in the first-line non-small lung cancer setting.

我們的PD-1計畫持續擴展。我們最近啟動了 cemiplimab 單藥治療一線非小細胞肺癌的 III 期臨床試驗計畫。這項在美國境外進行的 300 名患者的研究將招募 PD-L1 表達超過 50% 的患者，並將 cemiplimab 與標準鉑類雙藥療法進行比較。本研究的主要終點是無惡化存活期。我們計劃進行更多研究，包括非小細胞肺癌的聯合治療研究以及二線非小細胞肺癌的臨床試驗。提醒各位，儘管該領域近期遭遇了許多失敗，但目前只有一種獲批的 PD-1 或​​ PD-L1 藥物可用於一線非小細胞肺癌治療。

We also recently initiated a Phase III study in second-line cervical cancer. With our ongoing potentially pivotal study in basal cell carcinoma, this brings us to 4 potentially pivotal programs with our PD-1 antibody. We also have exploratory studies ongoing in melanoma and head and neck cancer, and we're also conducting and planning studies with cemiplimab in combination with our antibody to LAG3 in a variety of indications as well as a number of other combination approaches with cemiplimab including with our bispecifics.

我們最近也啟動了一項針對子宮頸癌二線治療的 III 期研究。結合我們正在進行的可能具有關鍵意義的基底細胞癌研究，這使我們有了 4 個可能具有關鍵意義的 PD-1 抗體計畫。我們目前也在黑色素瘤和頭頸癌領域進行探索性研究，並且正在進行和計劃將 cemiplimab 與我們的 LAG3 抗體聯合用於多種適應症的研究，以及 cemiplimab 與其他多種聯合療法的研究，包括與我們的雙特異性抗體聯合療法。

Turning now to these bispecifics. We will be presenting further positive data from our CD20xCD3 program, both as monotherapy and in combination with cemiplimab and b-cell malignancies at the December meeting of the American Society of Hematology, or ASH.

現在來看看這些雙特異性抗體。我們將於 12 月在美國血液學會 (ASH) 會議上公佈 CD20xCD3 計畫的更多積極數據，包括單藥治療以及與 cemiplimab 聯合治療 B 細胞惡性腫瘤的數據。

As a reminder, the CD20xCD3 program has been granted orphan drug designation for diffuse large cell -- b-cell lymphoma, or DLBCL. We're also conducting a combination study of our CD20xCD3 bispecific with cemiplimab in CD20-positive malignancies. We plan to put additional bispecifics into clinical trials over the next several years.

提醒大家，CD20xCD3 計畫已獲得治療瀰漫性大B細胞淋巴瘤（DLBCL）的孤兒藥資格認定。我們目前也正在進行一項研究，將我們的 CD20xCD3 雙特異性抗體與 cemiplimab 聯合用於 CD20 陽性惡性腫瘤的治療。我們計劃在未來幾年內將更多雙特異性抗體投入臨床試驗。

Fasinumab, our NFG antibody, continues to advance in the clinic. We're currently enrolling patients in the Phase III study in osteoarthritis pain, where we are investigating fasinumab compared to naproxen. We also plan to initiate a second study of fasinumab in osteoarthritis pain.

我們的NFG抗體Fasinumab在臨床試驗中持續取得進展。我們目前正在招募患者參與骨關節炎疼痛的 III 期研究，在該研究中，我們將研究 fasinumab 與萘普生的比較。我們也計劃啟動第二項關於fasinumab治療骨關節炎疼痛的研究。

I'll turn now to our mid- and earlier-stage pipeline. Nesvacumab is our antibody to ANGPTL3 for the treatment of severe forms of hyperlipidemia. We are planning Phase III studies in homozygous familial hypercholesterolemia, or homozygous FH, and Phase II studies in severe hypertriglyceridemia and in heterozygous familial hypercholesterolemia, or HetFH.

接下來，我將介紹我們的中早期研發管線。Nesvacumab 是我們針對 ANGPTL3 的抗體，用於治療嚴重高血脂症。我們計劃進行針對純合子家族性高膽固醇血症（或純合子 FH）的 III 期研究，以及針對嚴重高三酸甘油脂血症和雜合子家族性高膽固醇血症（或 HetFH）的 II 期研究。

We plan to initiate by year-end the Phase II study of Regeneron 2477, our Activin A antibody, in the ultrarare disease of fibrodysplasia ossificans progressiva, or FOP. We're also exploring the use of our Activin A antibody in combination trevogrumab, our GDF8 antibody, in muscle and metabolic disorders.

我們計劃在年底前啟動 Regeneron 2477（一種 Activin A 抗體）治療進行性骨化性纖維發育不良症（FOP）這種罕見疾病的 II 期研究。我們也正在探索將我們的 Activin A 抗體與我們的 GDF8 抗體 trevogrumab 聯合用於治療肌肉和代謝疾病。

Another exciting early-stage program is Regeneron 3500, our antibody to the interleukin-33 ligand, which is in the clinic, and we plan to investigate for asthma, COPD and other indications as both the monotherapy and in combination with dupilumab.

另一個令人興奮的早期項目是 Regeneron 3500，這是我們針對白細胞介素-33 配體的抗體，目前正在進行臨床試驗，我們計劃研究其作為單藥療法以及與度普利尤單抗聯合療法治療哮喘、慢性阻塞性肺病和其他適應症的療效。

With that overview, I'd like to turn the call over to you Bob Terifay.

綜上所述，接下來我將把電話交給鮑伯·特里費。

Thank you, George, and good morning, everyone. EYLEA or aflibercept continues to be the market-leading product among FDA-approved anti-VEGF agents for all of its approved indications in the United States.

謝謝你，喬治，大家早安。在美國，對於所有核准的適應症，EYLEA（阿柏西普）仍然是FDA批准的抗VEGF藥物中的市場領先產品。

U.S. EYLEA sales grew 12% year-over-year in the third quarter of 2017 in a market that grew by about 11%. Ex-U. S. sales grew by 20% year-over-year in a market that grew 13%. As was summarized by Len and George, we look forward to the potential of expanding the use of EYLEA in diabetic eye diseases, which we feel is a substantial potential opportunity.

2017 年第三季度，美國 EYLEA 的銷售額年增 12%，而同期市場整體成長了約 11%。前美國在市場整體成長 13% 的情況下，S 的銷售額比去年同期成長了 20%。正如 Len 和 George 所總結的那樣，我們期待 EYLEA 在糖尿病眼部疾病領域中得到更廣泛的應用，我們認為這是一個巨大的潛在機會。

Turning now to the recent launch of Dupixent or dupilumab in the United States for the treatment of adults with moderate to severe atopic dermatitis. Global sales for Dupixent in the third quarter were $89 million. This number almost entirely represents sales in the United States, since Dupixent only recently received regulatory approval in Europe at the end of September.

現在讓我們來看看最近在美國推出的Dupixent（或稱為dupilumab），用於治療中度至重度異位性皮膚炎成人患者。Dupixent 第三季全球銷售額為 8,900 萬美元。這個數字幾乎完全代表了美國的銷售額，因為Dupixent直到9月底才在歐洲獲得監管部門的批准。

We're pleased with the way the U.S. launch is tracking across a number of important metrics, and the commercial organizations are focused on delivering a successful launch.

我們對美國市場在多項重要指標上的進展感到滿意，商業機構也正致力於成功上市。

Let me begin with the physician perspective. As of last week, over 7,000 health care providers had written prescriptions for Dupixent for adult patients with moderate to severe atopic dermatitis. The prescription trajectory as measured by total prescriptions has remained strong and is trending ahead of comparable biologic launches in dermatology.

首先，我想從醫生的角度談談我的看法。截至上週，已有超過 7,000 名醫療保健提供者為患有中度至重度異位性皮膚炎的成年患者開立了 Dupixent 處方。從處方總量來看，處方趨勢依然強勁，並且領先於皮膚科領域類似的生物製劑上市。

In terms of new patient starts as assessed by new-to-brand prescriptions, we've seen on average approximately 750 new patients prescribed Dupixent each week and approximately 500 new patients starting therapy each week since the early part of the launch. Importantly, of the patients who've started on Dupixent, over 90% renew their prescription suggesting a high degree of patient and physician satisfaction.

從新患者開始使用（以新處方為準）來看，自上市初期以來，我們平均每週看到約 750 名新患者被處方 Dupixent，每週約有 500 名新患者開始接受治療。值得注意的是，在開始使用 Dupixent 的患者中，超過 90% 的人會續開處方，這表明患者和醫生都非常滿意。

On the market access side, we're happy to report that about 80% of commercial lives are now covered by health plans that have a published Dupixent policy. Of these patients, almost half have prior authorization to label. Or in other words, they can receive Dupixent by stepping through only topical therapy without requiring prior systemic therapy or a severity requirement.

在市場准入方面，我們很高興地報告，目前約 80% 的商業人壽保險已納入已公佈 Dupixent 保單的健康計劃。這些患者中，近一半事先獲得了標籤授權。換句話說，他們只需接受局部治療即可接受 Dupixent 治療，無需事先接受全身性治療或達到病情嚴重程度要求。

In addition to coverage at Express Scripts and CVS, Dupixent is also on formulary at Optum, Aetna, Anthem and United. In the coming weeks, we'll be launching unbranded direct-to-consumer television advertising to increase awareness of moderate to severe atopic dermatitis.

除了 Express Scripts 和 CVS 的承保範圍外，Dupixent 還被列入 Optum、Aetna、Anthem 和 United 的處方集。在接下來的幾周里，我們將推出無品牌直接面向消費者的電視廣告，以提高人們對中度至重度異位性皮膚炎的認識。

Outside of the United States, Dupixent has received regulatory approval in Europe, and we're preparing for launch in Germany. It's estimated that the addressable European patient population of moderate to severe atopic dermatitis patients is between 150,000 and 200,000 patients.

在美國以外，Dupixent 已在歐洲獲得監管部門批准，我們正在準備在德國上市。據估計，歐洲可治療的中度至重度異位性皮膚炎患者人數在 15 萬至 20 萬人之間。

A regulatory submission for Dupixent has been made in Japan with the decision expected in the first quarter of 2018. In addition to the ongoing launch in atopic dermatitis, we're also preparing to launch dupilumab in asthma. As mentioned earlier, we're on track to file a supplemental BLA submission to the FDA by the end of this year.

Dupixent 已在日本提交監管申請，預計將於 2018 年第一季做出決定。除了正在異位性皮膚炎領域進行的上市之外，我們還準備推出用於治療氣喘的度普利尤單抗。如前所述，我們正按計畫於今年底前向FDA提交補充生物製品許可申請。

Additionally, we and Sanofi plan to file a European regulatory submission in adult and adolescent patients in the first quarter of 2018.

此外，我們和賽諾菲計劃在 2018 年第一季向歐洲監管機構提交針對成人和青少年患者的申請。

Turning now to Kevzara or sarilumab, our IL-6 receptor antibody for the treatment of rheumatoid arthritis. Net global sales for the third quarter was $3 million. It's still very early given the Kevzara was approved to launched in the United States towards the end of May and reimbursement decisions for RA biologics take some time. Initial feedback from physicians has been positive, and we're working on building market access.

接下來我們來談談 Kevzara 或 sarilumab，這是我們用於治療類風濕性關節炎的 IL-6 受體抗體。第三季全球淨銷售額為 300 萬美元。鑑於 Kevzara 於 5 月底才獲准在美國上市，而類風濕性關節炎生物製劑的報銷決定需要一些時間，現在下結論還為時過早。醫生們的初步回饋是正面的，我們正在努力開拓市場。

We're happy to report that just recently, CVS Health announced that effective January 1, 2018, Kevzara will be designated as the preferred IL-6 receptor antibody on their national formulary. We've received EMA approval for Kevzara with launches in Germany and the Netherlands underway.

我們很高興地宣布，CVS Health 最近宣布，自 2018 年 1 月 1 日起，Kevzara 將被指定為其國家處方集中的首選 IL-6 受體抗體。Kevzara 已獲得 EMA 批准，目前正在德國和荷蘭上市。

Now let's discuss Praluent or alirocumab. Net sales in the third quarter were $49 million worldwide, with the U.S. accounting for $32 million of the total. While we continue to be disappointed with the uptake of the PCSK9 inhibitor class, we're encouraged by ongoing discussions with payers with respect to improvement in utilization management criteria and documentation requirements.

現在讓我們來討論一下Praluent或alirocumab。第三季全球淨銷售額為 4,900 萬美元，其中美國佔 3,200 萬美元。儘管我們對 PCSK9 抑制劑類藥物的普及程度仍然感到失望，但我們與支付方就改進利用管理標準和文件要求進行的持續討論令人鼓舞。

Recently, CVS Health announced that effective January 1, 2018, it would provide co-preferred access to Praluent through its CVS Caremark commercial formularies, which cover approximately 25 million lives. We remain optimistic about the long-term potential for this class. We anticipate a cardiovascular outcomes data for Praluent in early 2018 could have an impact on demand. We remain committed to our efforts to improve Praluent access and bring this important product to more patients who can benefit.

近日，CVS Health 宣布，自 2018 年 1 月 1 日起，將透過其 CVS Caremark 商業處方集提供 Praluent 的共同優先使用權，該處方集涵蓋約 2500 萬人。我們對這門課程的長期發展潛力依然保持樂觀。我們預計 Praluent 在 2018 年初公佈的心血管結果數據可能會對需求產生影響。我們將繼續致力於改善 Praluent 的可近性，並將這項重要產品帶給更多能夠受益的患者。

As George mentioned, cemiplimab, our PD-1 inhibitor program in immuno-oncology, is advancing with a regulatory submission in CSCC anticipated in the first quarter of 2018. We will co-promote cemiplimab in the United States with Sanofi Genzyme. As a reminder, we would distribute and book U.S sales.

正如喬治所提到的，我們的免疫腫瘤學PD-1抑制劑計畫cemiplimab正在推進，預計在2018年第一季向CSCC提交監管申請。我們將與賽諾菲健贊在美國共同推廣cemiplimab。再次提醒，我們將負責美國地區的銷售分銷和預訂。

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

接下來，我將把電話交給我們的財務長鮑伯·蘭德里。

Thanks, Bob, and good morning, everyone. Regeneron posted strong third quarter 2017 financial results. These positive results were driven by continued growth in our global EYLEA franchise, a strong U.S. Dupixent launch and a significant contribution of revenue from both our Sanofi and Bayer collaborations.

謝謝你，鮑勃，大家早安。再生元公司公佈了強勁的2017年第三季財務業績。這些積極成果得益於我們全球 EYLEA 產品線的持續成長、Dupixent 在美國的強勁上市以及我們與賽諾菲和拜耳合作的顯著收入貢獻。

During today's call, I'll discuss each of these matters in addition to highlighting changes to our full year 2017 guidance line items.

在今天的電話會議上，我將討論上述各項事宜，並重點介紹我們 2017 年全年業績指引的變化。

In the third quarter of 2017, we earned $3.99 per diluted share from non-GAAP net income of $470 million. This represents a year-over-year increase in non-GAAP diluted EPS and net income of 27% and 29%, respectively.

2017 年第三季度，我們實現非 GAAP 淨利 4.7 億美元，每股攤薄收益為 3.99 美元。這意味著非GAAP稀釋後每股盈餘和淨利分別較去年同期成長了27%和29%。

Regeneron's third quarter 2017 non-GAAP net income excludes noncash share-based composition expense, including the income tax effect. A full reconciliation of GAAP and non-GAAP earnings is set forth in our earnings release, which can be found on our website.

Regeneron 2017 年第三季非 GAAP 淨收入不包括非現金股份支付費用，包括所得稅影響。我們的獲利報告詳細列出了 GAAP 和非 GAAP 收益的調整情況，您可以在我們的網站上找到該報告。

Total revenues in the third quarter of 2017 were $1.5 billion, which represents year-over-year growth of 23% compared to the third quarter of 2016. Net product sales were $957 million in the third quarter of 2017 compared to $857 million in the third quarter of 2016, which represents year-over-year growth of approximately 12%.

2017 年第三季總營收為 15 億美元，與 2016 年第三季相比年增 23%。2017 年第三季淨產品銷售額為 9.57 億美元，而 2016 年第三季為 8.57 億美元，較去年同期成長約 12%。

EYLEA net product sales in the United States are $953 million in the third quarter of 2017 compared to $854 million in the third quarter of 2016, which represents an increase of 12%.

2017 年第三季度，EYLEA 在美國的淨產品銷售額為 9.53 億美元，而 2016 年第三季為 8.54 億美元，成長了 12%。

For the 9 months ended September 30, 2017, EYLEA net product sales in the United States were $2.73 billion versus $2.47 billion for the 9 months ended September 30, 2016, an increase of 11%.

截至 2017 年 9 月 30 日的 9 個月，EYLEA 在美國的淨產品銷售額為 27.3 億美元，而截至 2016 年 9 月 30 日的 9 個月為 24.7 億美元，成長了 11%。

We are reaffirming our estimated full year 2017 U.S. EYLEA net product sales growth guidance of approximately 10% over 2016. As a reminder, this is the last quarter where we will be providing U.S. EYLEA net sales guidance.

我們重申先前對 2017 年美國安理國際 (EYLEA) 淨產品銷售額成長的預期，預計比 2016 年成長約 10%。再次提醒大家，這將是我們最後一次提供美國安禮公司淨銷售額指引。

Similar to the previous 2 quarters of 2017, EYLEA experienced another decrease in U.S. distributor inventory levels, albeit slight during the third quarter, with distributor levels continuing to remain within our normal 1 to 2-week targeted range.

與 2017 年前兩個季度類似，安樂死美國分銷商的庫存水準在第三季度再次下降，儘管下降幅度不大，但分銷商的庫存水準仍然保持在我們正常的 1 到 2 週的目標範圍內。

Ex-U. S. EYLEA net product sales, which are recorded by our collaborator, Bayer, were $564 million in the third quarter of 2017 as compared to $471 million in the third quarter of 2016, representing a 20% increase on a reported basis.

前美國由我們的合作夥伴拜耳公司記錄的 S. EYLEA 淨產品銷售額在 2017 年第三季為 5.64 億美元，而 2016 年第三季為 4.71 億美元，按報告數據計算增長了 20%。

On an operational or constant currency basis, sales increased approximately 19%. For the 9 months ended September 30, 2017, ex-U. S. EYLEA net product sales were $1.59 billion versus $1.38 billion for the 9 months ended September 30, 2016, an increase of 16% on a reported basis and 18% on an operational basis.

以營運或固定匯率計算，銷售額成長約 19%。截至 2017 年 9 月 30 日的 9 個月（不包括美國）截至 2016 年 9 月 30 日的 9 個月，S. EYLEA 的淨產品銷售額為 15.9 億美元，而 2016 年同期為 13.8 億美元，按報告基準計算增長了 16%，按營運基準計算增長了 18%。

In the third quarter of 2017, Regeneron recognized $205 million from our share of net profits from EYLEA sales outside the United States. Total Bayer collaboration revenue for the third quarter 2017 was $237 million. Total Sanofi collaboration revenue was $245 million for the third quarter of 2017. The Sanofi collaboration revenue line item primarily consists of reimbursement of Regeneron incurred R&D expenses, reimbursement of Regeneron incurred commercialization-related expenses and the recognition of deferred revenue from the antibody and immuno-oncology upfront payments, partly offset by our share of losses in connection with commercialization of antibodies.

2017 年第三季度，Regeneron 從 EYLEA 在美國以外地區的銷售淨利潤中確認了 2.05 億美元。2017 年第三季拜耳合作總營收為 2.37 億美元。2017 年第三季度，賽諾菲合作總營收為 2.45 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，以及確認抗體和免疫腫瘤預付款的遞延收入，部分被我們應承擔的抗體商業化相關損失所抵消。

In the third quarter of 2017, our share of losses in connection with the commercialization of Dupixent, Praluent and Kevzara was $98 million compared to a loss of $122 million in the second quarter of 2017 and a loss of $112 million in the third quarter of 2016. The decrease in our share of losses was primarily based upon the profit contribution from increased third quarter Dupixent sales and lower alliance commercial expenses for Praluent, offset by a modest increase in our alliance commercial expenses for Dupixent and Kevzara.

2017 年第三季度，我們在 Dupixent、Praluent 和 Kevzara 商業化方面的虧損份額為 9,800 萬美元，而 2017 年第二季度虧損 1.22 億美元，2016 年第三季虧損 1.12 億美元。我們虧損份額的減少主要得益於第三季 Dupixent 銷售額的成長和 Praluent 聯盟商業費用的降低，但被 Dupixent 和 Kevzara 聯盟商業費用的適度增長所抵消。

Global sales of Dupixent, Praluent and Kevzara as recorded by our collaborator, Sanofi, for the third quarter of 2017 were Dupixent $89 million, Praluent $49 million and Kevzara $3 million. For both Dupixent and Kevzara, the sales were almost exclusively U.S.-based. As stated by our collaborator, Sanofi, on their earnings call last week, Dupixent third quarter 2017 net sales included modest wholesaler inventory stocking, not unexpected in the $89 million sales figures, is a true representation of the underlying demand.

根據我們的合作夥伴賽諾菲統計，2017 年第三季 Dupixent、Praluent 和 Kevzara 的全球銷售額分別為：Dupixent 8,900 萬美元，Praluent 4,900 萬美元，Kevzara 300 萬美元。Dupixent 和 Kevzara 的銷售額幾乎全部來自美國。正如我們的合作夥伴賽諾菲在上週的財報電話會議上所說，Dupixent 2017 年第三季的淨銷售額包含了適度的批發商庫存，這在 8,900 萬美元的銷售額中並不意外，真實反映了潛在的需求。

While we are encouraged with the reduction in our share of alliance losses on the antibody collaboration in the third quarter of 2017, I want to continue to highlight that the alliance's profitability will continue to be negatively impacted by increased global launch expenses to support Kevzara and Dupixent. As a result, we are expecting a higher alliance loss in connection with commercialization of antibodies in the fourth quarter of 2017 than what was realized in the third quarter of 2017.

儘管我們對 2017 年第三季抗體合作聯盟虧損份額的減少感到鼓舞，但我仍要強調，由於支持 Kevzara 和 Dupixent 的全球上市費用增加，聯盟的盈利能力將繼續受到負面影響。因此，我們預計 2017 年第四季與抗體商業化相關的聯盟損失將高於 2017 年第三季的損失。

The third quarter 2017 Sanofi collaboration revenue also benefited from an acceleration of the recognition of deferred revenue in connection with the termination of the antibody discovery agreement on December 31, 2017.

2017 年第三季賽諾菲合作收入也受惠於 2017 年 12 月 31 日抗體發現協議終止後，遞延收入的確認加速。

$130 million of 2017 annual funding from Sanofi under the antibody discovery agreement was fully utilized during the first 9 months of 2017. Due to this utilization, we expect Sanofi's reimbursement of Regeneron research and development expenses in the fourth quarter 2017 to be lower than any of the 3 previous quarters.

根據抗體發現協議，賽諾菲在 2017 年提供的 1.3 億美元年度資金在 2017 年前 9 個月內全部用完。由於這種利用方式，我們預計賽諾菲在 2017 年第四季對 Regeneron 研發費用的報銷將低於前三個季度中的任何一個季度。

In the third quarter of 2017, other revenue was $62 million versus $27 million during the third quarter of 2016. This increase was primarily due to the reimbursements from our collaborator, Teva, for the development of fasinumab. For further details, you can find a summary of the components of other revenue in the MD&A section of our 10-Q.

2017 年第三季其他營收為 6,200 萬美元，而 2016 年第三季為 2,700 萬美元。這一增長主要是由於我們的合作方梯瓦製藥公司為開發法西單抗支付了費用。有關更多詳細信息，您可以在我們 10-Q 的 MD&A 部分找到其他收入組成部分的摘要。

Turning now to expenses. Non-GAAP R&D expenses were $460 million for the third quarter of 2017. Our non-GAAP unreimbursed R&D expense, which is calculated as the total non-GAAP R&D expense less R&D reimbursement from our collaborators, was $227 million in the third quarter of 2017. Our press release includes all the information that's required to calculate unreimbursed non-GAAP R&D expense. We are lowering and tightening our full year 2017 guidance for non-GAAP unreimbursed R&D to be in the range of $885 million to $915 million from our previous guidance of $925 million to $965 million.

接下來談談費用。2017 年第三季非 GAAP 研發費用為 4.6 億美元。2017 年第三季度，我們的非 GAAP 未報銷研發費用（計算方法為非 GAAP 研發總費用減去合作方的研發報銷）為 2.27 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。我們將 2017 年全年非 GAAP 未報銷研發支出預期從先前的 9.25 億美元至 9.65 億美元下修並收緊至 8.85 億美元至 9.15 億美元。

Non-GAAP SG&A expense was $259 million for the third quarter of 2017. It represents a slight decrease from the previous quarter. Given our 9-month actual results and forecasted fourth quarter spend, we are tightening and lowering our full year 2017 guidance of non-GAAP SG&A to $1.07 billion to $1.1 billion from our previous guidance range of $1.12 billion to $1.16 billion.

2017 年第三季非 GAAP 銷售、一般及行政費用為 2.59 億美元。這比上一季略有下降。鑑於我們前 9 個月的實際業績和預測的第四季度支出，我們將 2017 年全年非 GAAP 銷售、一般及行政費用指導範圍從之前的 11.2 億美元至 11.6 億美元下調至 10.7 億美元至 11 億美元。

Based on this revised guidance, you will see that we are forecasting a higher SG&A spend level for the fourth quarter of 2017, resulting from the delayed timing of third quarter spend. In addition, as I previously mentioned, we are expecting higher fourth quarter incremental global spend on our 2 recently FDA and EMA approved launches. Dupixent and Kevzara as well as prelaunch expenses for the anticipated 2018 U.S. approvals for dupilumab in cutaneous squamous cell carcinoma in the dupilumab asthma indication.

根據這項修訂後的指導意見，您將會看到，由於第三季支出延遲，我們預測 2017 年第四季的銷售、一般及行政費用支出水準將會更高。此外，正如我之前提到的，我們預計第四季度全球新增支出將增加，用於我們最近獲得 FDA 和 EMA 批准的兩款產品的上市。Dupixent 和 Kevzara 以及 2018 年美國批准 dupilumab 用於治療皮膚鱗狀細胞癌和 dupilumab 用於治療氣喘的上市前費用。

Sanofi reimbursement of Regeneron commercialization-related expenses, a line item found within Sanofi collaboration revenue, was $90 million for the third quarter of 2017. We are tightening and lowering our full year 2017 guidance of Sanofi reimbursement of Regeneron commercialization-related expenses to $350 million to $375 million from our previous guidance range of $370 million to $400 million.

2017 年第三季度，賽諾菲向 Regeneron 支付的商業化相關費用（該費用包含在賽諾菲合作收入中）為 9,000 萬美元。我們將 2017 年全年賽諾菲 Regeneron 商業化相關費用的報銷預期從先前的 3.7 億美元至 4 億美元下調至 3.5 億美元至 3.75 億美元。

Non-GAAP cost of goods sold and cost of collaboration and contract manufacturing increased for the 3 months ended September 30, 2017, compared to the same period in 2016, principally due to an increase in start-up costs and validation activities for our Limerick commercial manufacturing facility.

截至 2017 年 9 月 30 日的三個月內，非 GAAP 銷售成本和合作及合約製造成本較 2016 年同期有所增加，主要原因是我們在利默里克的商業製造工廠的啟動成本和驗證活動增加。

Turning now to taxes. Our effective tax rate for the third quarter of 2017 was 31% as compared to 28% for the third quarter of 2016. For the full year 2017, we are tightening and lowering guidance for our effective tax rate to be in the range of 26% to 29% from the previous range of 27% to 31%. The updated guidance reflects higher actual and forecasted tax deductions from stock options. As stated on previous earning calls, there will be volatility in our effective tax rate on a quarter-to-quarter basis since the tax benefit of stock-based compensation is included based on actual exercises in the quarter.

接下來談談稅務問題。2017 年第三季的實際稅率為 31%，而 2016 年第三季的實際稅率為 28%。對於 2017 年全年，我們將收緊並降低實際稅率的預期，從先前的 27% 至 31% 的區間下調至 26% 至 29% 的區間。更新後的指導意見反映了股票選擇權實際和預測的稅收抵扣額增加。如同先前的財報電話會議中所述，由於股票選擇權激勵的稅收優惠是根據季度內的實際行使情況計算的，因此我們的實際稅率會逐季度波動。

We expect to experience this volatility in the fourth quarter of 2017, as the majority of our options are issued in December and typically a large number of options vest and/or exercised in the fourth quarter. As a result, we expect our fourth quarter 2017 effective tax rate to be significantly below both the third quarter and full year 2017 tax rates.

我們預計 2017 年第四季將出現這種波動，因為我們的大部分選擇權都是在 12 月發行的，而且通常第四季會有大量選擇權歸屬和/或行使。因此，我們預計 2017 年第四季的實際稅率將遠低於 2017 年第三季和全年的稅率。

From a cash flow and balance sheet perspective, we ended the third quarter of 2017 with cash and marketable securities of $2.7 billion. Our capital expenditures for the 3 and 9 months ended September 30, 2017, were $60 million and $165 million, respectively. We are tightening our full year 2017 capital expenditures guidance to be in the range of $265 million to $285 million from our previously provided range of $250 million to $285 million.

從現金流量和資產負債表的角度來看，截至 2017 年第三季末，我們擁有現金和有價證券 27 億美元。截至 2017 年 9 月 30 日的 3 個月和 9 個月期間，我們的資本支出分別為 6,000 萬美元和 1.65 億美元。我們將 2017 年全年資本支出預期從先前給出的 2.5 億美元至 2.85 億美元收緊至 2.65 億美元至 2.85 億美元。

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

那麼，我想把電話轉回給瑪妮莎。

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

謝謝你，鮑伯。Paulette，現在我們想開始問答環節。為了節省時間，請您只提一個問題。通話結束後，我們會在辦公室解答後續問題。

(Operator Instructions) And our first question comes from Chris Raymond from Piper Jaffray.

（操作說明）我們的第一個問題來自 Piper Jaffray 公司的 Chris Raymond。

Just a question on the Dupixent prescriber base, if you don't mind. I just noticed in previous communications, you guys have talked about an initial target base, I think, of 7,000 derms with previous biologic experience. I think I heard today, Bob, talk about having had 7,000 docs write a script for the drug. So maybe can you just talk about that mix? Is that current 7,000 base -- is that the initial target? Or were there others that you maybe didn't expect? And maybe talk about the road in front of you here in terms of getting other docs to prescribe the drug.

如果您不介意的話，我想問一下關於Dupixent處方醫生群體的問題。我剛剛注意到，在先前的溝通中，你們提到最初的目標群體，我認為是7000名有生物製劑經驗的皮膚科醫生。鮑勃，我今天好像聽到有人說有 7000 名醫生為這種藥開了處方。所以，您能談談這個混音嗎？目前7000人的基礎－這是最初的目標嗎？或是有其他你意想不到的人嗎？或許還可以談談你目前面臨的挑戰，例如如何讓其他醫生開這種藥。

Yes, so, Chris, you're correct. Our original target audience were physicians who have written a biologic for psoriasis in the past. And that was slightly over 7,000 patients. What we have found when we've gone out to the dermatologist offices is there is other dermatologists in those offices who take an interest in atopic dermatitis patients and have started to use the product. For the future, what we anticipate is that we will see other prescribers as patients become aware through our direct-to-consumer campaign on the severity of the condition and the need to seek out a dermatologist and that there could be an increased urgency to treat over time.

是的，克里斯，你說得對。我們最初的目標受眾是過去曾開立過銀屑病生物製劑處方的醫生。總共有7000多名患者。我們走訪皮膚科醫生診所後發現，有些皮膚科醫生對異位性皮膚炎患者很感興趣，並且已經開始使用該產品。展望未來，我們預計，隨著患者透過我們的直接面向消費者的活動意識到病情的嚴重性以及尋求皮膚科醫生的必要性，其他醫生也會開始開這種藥，而且隨著時間的推移，治療的緊迫性可能會增加。

Operator, next question please.

操作員，請問下一個問題？

Our next question comes from Geoffrey Porges from Leerink.

下一個問題來自 Leerink 公司的 Geoffrey Porges。

Number of things, but perhaps we can talk, you suggested sort of part of life cycle management strategy for EYLEA alluded to on the call. But is there anything you could talk about first with respect to the prefilled syringe offering for EYLEA? And then secondly, do you have anything in mind that you could do with Dupixent given how important it's going to be to the company to reduce the dosing frequency with the product in some new formulation or preparation?

有很多事情，但或許我們可以談談，您在電話中提到的安永生命週期管理策略的一部分。但關於EYLEA的預充式註射器產品，您能否先談什麼？其次，考慮到降低Dupixent的給藥頻率對公司來說非常重要，您是否考慮過採用某種新配方或製劑來改進該產品？

All right. Thanks, Geoff. So we probably don't want to get into Dupixent given the competitive aspect of that space. But we continue to look at also to different ways to create value. We can assure you of that. And in terms of EYLEA in the prefilled syringe, we had 2 issues. Genentech was ahead of us with the prefilled syringe and now they're fully launched. But I think, as you saw in Bob's report, our market share was steady. And so -- and that has not really created a problem for us. Nevertheless, we're still moving forward with ours, and I think we expect to have a filing, perhaps, sometime in the first half of next year or so. It's a complicated business, the prefilled syringe, because of the sterilization requirements when you're dealing with eye diseases. It took Genentech, I don't know, quite a long time to get there, and we hope to be not too far behind them.

好的。謝謝你，傑夫。鑑於 Dupixent 領域的競爭形勢，我們可能不想涉足這個領域。但我們也將繼續探索創造價值的不同途徑。我們可以向你保證這一點。至於預充式註射器中的愛立信，我們遇到了兩個問題。基因泰克公司在預充式註射器方面領先我們，現在他們已經全面推出了該產品。但我認為，正如你在鮑勃的報告中看到的那樣，我們的市場份額保持穩定。所以——但這並沒有真正給我們造成問題。儘管如此，我們仍在推進我們的計劃，我認為我們預計可能會在明年上半年左右提交申請。預充式註射器是一個複雜的行業，因為在治療眼科疾病時，對消毒有嚴格的要求。基因泰克花了相當長的時間才達到現在的水平，我們希望不要落後他們太遠。

Our next question comes from Ying Huang from Bank of America Merrill Lynch.

下一個問題來自美國銀行美林證券的黃穎。

I have another question on Dupixent. Right now, Sanofi commented that most of the patients on Dupixent are the severe patients with atopic dermatitis. When do you think this drug can penetrate into the moderate patient segment? And then, also, are you planning to increase investment in Praluent now that the court gave you a favored ruling? Or you have to wait until you have the ODYSSEY OUTCOME?

我還有一個關於Dupixent的問題。賽諾菲表示，目前使用 Dupixent 的患者大多是患有嚴重異位性皮膚炎的患者。您認為這種藥物何時才能被中度患者族群所接受？另外，既然法院做出了對你有利的裁決，你是否計劃增加對 Praluent 的投資？或者你必須等到獲得 ODYSSEY 結果？

So with regards to Dupixent, Sanofi was correct. What we're seeing is that physicians are initiating Dupixent therapy in the patients with severe atopic dermatitis. Now what is encouraging is that the patients are responding. So even in those very, very severe patients, we're getting a good response. We do anticipate that physicians will become more and more comfortable with using a biologic for a condition they have not used one for before, which is atopic dermatitis. And that we should see expansion into moderate AD over the next several months. That should also be helped by our direct-to-consumer campaign. With regards to investment in Praluent. I think we've been very prudent this year. We have managed our investment, focused in on where we can best get business, which is primarily on education, and we'll continue to be modest on our spend until we get the OUTCOMES data. And we move forward with the court case.

所以就Dupixent而言，賽諾菲的說法是正確的。我們看到的是，醫生開始對患有嚴重異位性皮膚炎的患者進行Dupixent治療。令人鼓舞的是，患者們正在接受治療並取得療效。所以即使是那些病情非常嚴重的患者，我們也得到了很好的治療效果。我們預計，醫生們會越來越樂於使用生物製劑治療他們以前從未用生物製劑治療過的疾病，即異位性皮膚炎。我們應該會在未來幾個月看到中度阿茲海默症的蔓延。我們的直接面向消費者的行銷活動也應該對此有所幫助。關於對 Praluent 的投資。我認為我們今年一直非常謹慎。我們已經妥善管理了投資，專注於我們能夠獲得最佳業務的領域，主要是教育領域，在我們獲得成果數據之前，我們將繼續保持適度的支出。我們將繼續推進訴訟程序。

Our next question comes up from Robyn Karnauskas from Citi.

下一個問題來自花旗銀行的 Robyn Karnauskas。

So I just wanted to ask a little bit about the pipeline because I thought you did a great job articulating the EYLEA business and how it can grow. So just the next leg of growth, maybe talk a little bit about how you envision the checkpoint -- your checkpoint drug being a next leg of growth. And what has to happen for that to succeed?

所以我想稍微問一下關於產品線的問題，因為我覺得你對安樂雅的業務及其發展方式的闡述非常出色。所以，接下來的發展階段，也許可以談談你對檢查點的設想——你的檢查點藥物是下一個發展階段。要實現這一點，需要滿足哪些條件？

Robyn, I didn't -- I'm not sure I heard the question. Was it -- were you asking about the immuno-oncology program? Is that what your question was about?

羅賓，我沒有——我不確定我是否聽到了這個問題。您問的是免疫腫瘤學計畫嗎？你的問題是關於這個的嗎？

Oncology program. How do you see that being a next leg of growth and what has to happen? And how do you see that playing out over the next few years? How do you see that shaping up?

腫瘤科項目。您認為這會是下一個成長階段嗎？需要發生哪些變化？你認為未來幾年這種情況會如何發展？你覺得事情會如何發展？

Yes. Okay. George may have some comments on it. But I think the most important thing that he pointed out to me in some of his remarks is that despite all the efforts, despite everybody viewing this is an incredibly crowded space, there is only one anti-PD-1 or PD-L1 that's been approved in frontline -- first-line lung cancer. And that is sort of the biggest opportunity of all, which we are now busy enrolling a study in that indication in the [greater than] 50%. Beyond that, of course, combinations and George mentioned LAG3 and bispecifics, and I think we have some pretty encouraging bispecific data coming up at the next meeting.

是的。好的。喬治或許對此有一些看法。但我認為他在一些演講中向我指出的最重要的一點是，儘管大家付出了種種努力，儘管每個人都認為這是一個非常擁擠的領域，但只有一種抗 PD-1 或​​ PD-L1 藥物被批准用於一線治療肺癌。而這正是最大的機遇，我們現在正忙著招募符合該適應症（超過 50%）的患者進行研究。當然，除此之外，還有組合療法，喬治提到了 LAG3 和雙特異性抗體，我認為我們在下次會議上會有一些非常令人鼓舞的雙特異性抗體數據。

Right. I mean, it's just worth noting. Obviously, it's going to be a long-term growth opportunity over, we think, a long period of time by adding additional opportunities to it and combining things. We think we have one of the strongest portfolio of combination opportunities that we've already started studying in the clinic and more will follow. But even the very first indication should not be underestimated. If you look at the cutaneous squamous cell carcinoma, there's enormous need there. And the actual -- it is actually that the number of cases is huge. And it's been largely ignored because of the vast, vast majority of them can be treated surgically. But because there is something on the order of a million or 2 million cases. And even though something like over greater than 95% are treated surgically, that still leaves an opportunity of unresectable or metastatic disease, which is on the order of magnitude of melanoma. And like I said, I think it was largely ignored by the community because of the perspective that though it was one of the, if not the most common cancers, afflicting patients. The vast, vast majority are treated successfully with these Mohs type surgeries and so forth. So the important thing to add is even that first opportunity, there's a lot of needed there, there's a lot of patients who are failures or cannot be treated with surgery and that opportunity is on the order of magnitude of melanoma, which as we know was a huge growth driver for the 2 original PD-1 agents.

正確的。我的意思是，這值得一提。顯然，我們認為，透過不斷增加新的機會和整合各種資源，這將在很長一段時間內成為一個長期的成長機會。我們認為我們擁有最強大的聯合療法組合之一，我們已經開始在臨床上研究這些療法，未來將有更多療法進入臨床研究。但即使是最初的跡像也不容小覷。如果你看看皮膚鱗狀細胞癌，你會發現那裡的需求非常巨大。而實際情況是──病例數非常龐大。而且由於絕大多數病例都可以透過手術治療，因此這個問題在很大程度上被忽視了。但因為病例數大約有百萬到兩百萬例。即使超過 95% 的病例都以手術治療，仍有可能出現無法切除或轉移性疾病，其嚴重程度與黑色素瘤相當。正如我所說，我認為它在很大程度上被社會所忽視，因為人們普遍認為，儘管它是最常見的癌症之一，甚至是最常見的癌症，但它仍然困擾著許多患者。絕大多數患者都透過莫氏手術等方法成功治癒。因此，需要補充的重要一點是，即使是第一個機會，也存在許多需求，有很多患者手術失敗或無法手術治療，而這個機會的規模與黑色素瘤相當，我們知道，黑色素瘤是最初兩種 PD-1 藥物的巨大增長動力。

Our next question comes from Matthew Harrison from Morgan Stanley.

下一個問題來自摩根士丹利的馬修·哈里森。

I guess, I was hoping you could talk a little bit about PANORAMA and just talk to us about you obviously outlined the size of the markets for what AMD and DME. How do you view diabetic retinopathy relative to the size of those other markets and how do you see that being a growth driver for EYLEA, if you were to have a successful study?

我想，我原本希望您能談談 PANORAMA，並和我們談談您顯然概述的 AMD 和 DME 的市場規模。您如何看待糖尿病視網膜病變相對於其他市場的規模？如果您成功進行相關研究，您認為糖尿病視網膜病變如何成為EYLEA的成長驅動力？

So I'm going to let George talk about PANORAMA and why we have a reasonably high degree of confidence in that study in just a second. I just want to say in terms of the market opportunity, the lowest hanging fruit, obviously, is the proliferative diabetic retinopathy because people recognize that as really vision-threatening and most people get some sort of the laser that's been going on for decades as we mentioned. So it's hard to know exactly how many people there, but that represents a pretty big opportunity. And with this clarity study that was published in the Lancet, where you not only saw better visual acuity outcomes in the year, you saw less hemorrhages, you saw less macular edema, less of the complications that you're so worried about, which is why you want to treat proliferative diabetic retinopathy. But beyond that, even the treatment of severe diabetic retinopathy, which is non-proliferative, is really in its infancy. There isn't quite the same perceived urgency there, but I think if we can show that we can reverse that, I think that, that's going to sort of maybe change people's view on whether or not people should get treated or should they wait, which is the current thing, wait for them to get the complications. Perhaps, it is better to treat early. And now George can comment a little bit about on the study itself and why.

接下來，我將讓喬治談談 PANORAMA 研究，以及為什麼我們對這項研究有相當高的信心。我想說的是，就市場機會而言，最容易實現的顯然是增殖性糖尿病視網膜病變，因為人們認識到這種疾病確實會威脅視力，而且大多數人都會接受某種激光治療，正如我們提到的，這種治療已經進行了幾十年。所以很難確切知道那裡有多少人，但這代表著一個巨大的機會。這項發表在《刺胳針》上的清晰度研究不僅顯示，一年內患者的視力結果有所改善，出血減少，黃斑水腫減少，併發症也減少了，而這些併發症正是我們如此擔心的，因此我們才想要治療增殖性糖尿病視網膜病變。但除此之外，即使是嚴重的糖尿病視網膜病變（非增殖性）的治療，仍處於起步階段。雖然目前還沒有出現同樣的緊迫感，但我認為，如果我們能夠證明我們可以扭轉這種局面，那麼這或許會改變人們對是否應該治療還是應該等待的看法，而目前的情況是，等待出現併發症。或許，及早治療效果更好。現在喬治可以對這項研究本身及其原因發表一些評論了。

I think Len made all the important points, and let me just echo. The most important point is that, where the need right now in diabetic retinopathy is perceived as the most urgent as in proliferative eye disease, there's roughly 0.5 million such patients in the United States. And 80% or 400,000 of them receive ablative laser therapy, the most serious of laser therapies. And now with the clarity data, what has a head-to-head comparison showing by every measure from visual acuity to just as importantly having the risk of developing vitreous hemorrhages reducing by almost 2/3 the risk of developing macular edema. This is something that I think patients deserve to have access to and deserve to get in this setting because without ablating their retinas, they can have better vision and better outcomes and avoid catastrophic events like vitreous hemorrhages. I think that the 2 million or so people who have diabetic retinopathy that's considered little less urgent, I think that this could be an important advance for those patients as well and already all the existing data suggest that, but I think that there'll be probably slower uptick. It'll be a longer haul to change the practice of medicine there where many of those patients are treated with the wait-and-see attitude because they haven't had a drug like EYLEA thus far. But I really do think in proliferative eye disease, 500,000 patients, those patients deserve to get a therapy that's been shown in a head-to-head study to be so substantially beneficial, not only in terms of visual acuity, but in terms of preventing catastrophic outcomes, which is why they're treated so urgently with ablative therapy.

我認為 Len 已經把所有要點都說清楚了，我只想重複一下。最重要的一點是，目前糖尿病視網膜病變和增殖性眼疾的需求最為迫切，美國約有 50 萬此類患者。其中 80%（即 40 萬人）接受了剝脫性雷射治療，這是最嚴重的雷射治療。現在有了清晰度數據，直接對比顯示，從視力到同樣重要的玻璃體出血風險降低近 2/3，黃斑水腫的風險降低，各項指標均顯示出優勢。我認為患者應該有機會獲得這種治療，並且應該在這種環境下接受治療，因為無需切除視網膜，他們就能擁有更好的視力和更好的治療效果，並避免玻璃體出血等災難性事件。我認為，對於大約 200 萬患有糖尿病視網膜病變的人來說，這雖然不那麼緊急，但我認為這對他們來說也是一個重要的進步，而且所有現有的數據都表明了這一點，但我認為增長速度可能會比較慢。改變那裡的醫療實踐將是一個漫長的過程，因為那裡的許多患者都採取了觀望態度，因為他們至今還沒有使用像 EYLEA 這樣的藥物。但我真的認為，在增生性眼疾中，有 50 萬名患者，這些患者應該得到一種療法，這種療法在直接對比研究中已被證明具有顯著的益處，不僅在視力方面，而且在預防災難性後果方面也是如此，這就是為什麼他們要如此緊急地接受消融療法治療的原因。

And then just the last point on that, Robyn, is that in the competitive environment, it's less acute there, obviously, because the near-term competition hasn't begun any diabetic macular edema studies. And by the way, in our DME studies, we looked at the same endpoint for the patients with diabetic retinopathy in our PANORAMA study because our DME studies were in patients with diabetic retinopathy. But we were treating their DME, their diabetic retinopathy improved just the way we hoped and expect that it will improve in PANORAMA, which is what the FDA just asked us to do is to do a study in patients without the DME component and that's why we have some, I would say, reason behind confidence in that study.

羅賓，關於這一點，最後一點是，在競爭激烈的環境中，這種情況顯然不太嚴重，因為近期競爭對手還沒有開始任何糖尿病性黃斑水腫的研究。順便說一下，在我們的 DME 研究中，我們觀察了 PANORAMA 研究中糖尿病視網膜病變患者的相同終點，因為我們的 DME 研究對像是糖尿病視網膜病變患者。但是，我們正在治療他們的糖尿病黃斑水腫（DME），他們的糖尿病視網膜病變也如我們所願有所改善，並且我們預計在 PANORAMA 研究中也會如此。 FDA 剛剛要求我們進行一項針對沒有 DME 成分的患者的研究，這就是為什麼我們對這項研究有信心的原因。

Our next question comes from Cory Kasimov from JPMorgan.

我們的下一個問題來自摩根大通的科里·卡西莫夫。

I was curious for asthma. How important do you think baseline eosinophil counts will be when thinking about which patients to prescribe Dupixent in the real world?

我對氣喘很有興趣。在現實世界中，考慮開立Dupixent處方給哪些患者時，您認為基線嗜酸性粒細胞計數有多重要？

Well, I mean, let's just review what the facts are. If you look at our data and you can't make these cross-study comparisons and take them overly seriously. But if you look at our data, we enrolled a very broad population, but the drug works better the higher the eosinophil count is. And if you look in our high eosinophilic count, I would argue some of the best data that's been presented with any of the biologics, including a robust very significant effect on exacerbations as well as the effect on lung function. But we also were able to enroll a very broad population in all 3 of our studies. So we would hope and argue that it doesn't really matter if you're worried about treating the eosinophilic type, which has more exacerbations and may represent the more urgent need. We think our drug will offer a terrific opportunity, especially with the differentiating factors that we talked about around pulmonary function and if you happen to have another allergic disease. And these things do run in packs if you happen to also have severe atopic dermatitis or moderate to severe, you would get 2 treatments for the cost of one. But of course, we also think about that across the broad spectrum. Ours is the first biologic to be studied, of course, that consistently in all of our trials. So no matter how you look at our data, we like it. We and Sanofi are very pleased with the data.

嗯，我的意思是，我們先來回顧一下事實。如果你查看我們的數據，你會發現無法進行這些跨研究比較，也不應該過度認真看待這些比較結果。但如果你看一下我們的數據，我們招募了非常廣泛的人群，但嗜酸性粒細胞計數越高，藥物的效果就越好。如果你看看我們較高的嗜酸性粒細胞計數，我認為這是我們所有生物製劑中呈現的最好的數據之一，包括對病情加重的顯著療效以及對肺功能的影響。但是，我們的三項研究都納入了非常廣泛的人群。因此，我們希望並認為，如果您擔心治療嗜酸性粒細胞型（這種類型病情加重較多，可能代表著更迫切的需求），其實並不重要。我們認為我們的藥物將帶來絕佳的機會，尤其是在我們討論過的肺功能差異因素方面，以及如果您恰好患有其他過敏性疾病的情況下。而且這些東西都是成套出售的；如果你剛好患有嚴重的異位性皮膚炎或中度至重度異位性皮膚炎，那麼你只需支付一份的費用就能獲得兩份治療。當然，我們也會從更廣泛的層面來考慮這個問題。當然，我們的生物製劑是第一個在所有試驗中都一致研究的生物製劑。所以無論從哪個角度來看我們的數據，我們都滿意。我們和賽諾菲對這些數據非常滿意。

Yes, maybe just to put into a little bit of context as Len said, we did 3 pivotal studies. And in the overall population, as Len said, it's hard to compare across studies, but I don't think anybody would argue that. In the overall population, even in the worst of the 3 studies in terms of the numbers, they look quite comparable to the highest eosinophilic groups for either approved biologics or for near-term biologics that are coming down there. But -- and obviously, we also have even better data in the high eosinophilic patients. And as well as that, I think, the most important differentiator also has to be not only do we have comparable results to what others have in the high EOS in the overall population, but we have these lung function results. And I think that this has been just -- as we try to communicate during our prepared remarks, this has been somewhere where the field has been going away from only because biologics to date have not been doing such a good job. If you remember the way XOLAIR got approved, up until that point, lung function was the standard for approval. But because XOLAIR had no effect on lung function, they switched the focus to these exacerbations, which obviously, are very important and so forth. But if you know anybody with asthma, you know that the thing that they suffer from and they worry about on a day-to-day basis is the shortness of breath that they can suffer from with a little bit of exercise or some other trigger that they might be suffering from. And I think it's really important to recognize that the results on lung function are really impressive, not only on the overall population, but even more impressive in the high eosinophilic population. So once again, I think if anybody honestly looks at the data and looks at the effects not only in the overall population, not only exacerbations, but also on lung function, you would think that this is the treatment that patients deserve to be given to benefit their condition and not only the high eosinophilic patients, but the overall population.

是的，正如 Len 所說，為了提供一些背景信息，我們進行了 3 項關鍵研究。正如 Len 所說，在整體人群中，很難對不同研究進行比較，但我認為沒有人會對此提出異議。即使在 3 項研究中數據最差的一項中，總體人群的情況也與已批准的生物製劑或即將上市的生物製劑的最高嗜酸性粒細胞組相當。但是——顯然，我們在嗜酸性粒細胞增多的患者中也有更好的數據。除此之外，我認為最重要的差異還在於，我們不僅在整體人群中高 EOS 方面取得了與其他研究者相當的結果，而且我們還取得了這些肺功能結果。我認為，正如我們在準備好的演講稿中試圖傳達的那樣，這正是該領域一直在偏離的方向，僅僅是因為迄今為止生物製劑的效果並不理想。如果你還記得 XOLAIR 的核准流程，就會知道，在此之前，肺功能是核准的標準。但由於 XOLAIR 對肺功能沒有影響，他們將重點轉移到這些病情加重上，這顯然非常重要等等。但如果你認識任何患有氣喘的人，你就會知道他們每天都在遭受和擔心的是，他們可能會因為稍微運動一下或受到其他一些誘因而出現呼吸困難。我認為非常重要的是要認識到，肺功能方面的結果非常令人印象深刻，不僅在總體人群中如此，而且在高嗜酸性粒細胞人群中更是如此。所以，我認為，如果有人認真地查看數據，並查看其對整體人群、病情加重以及肺功能的影響，就會認為這是患者應該接受的治療，以改善他們的病情，不僅是嗜酸性粒細胞增多的患者，而且是整個人群。

Yes, I also think that you can't ignore mechanism here. There's been a lot of claims that people are getting to the fundamental mechanisms of allergic disease. And it's hard to say that you're at the fundamental mechanism of allergic disease if in one allergic disease it works and another allergic disease it doesn't work. And it's hard to say you're getting it to the fundamental basis of the allergic disease if you're only affecting part of the disease like exacerbations and not affecting lung function. It's hard to say you're getting at the fundamental part of the disease if in eosinophilic esophagitis, you can lower your eosinophils, but you can't improve the symptoms of the actual inflammation that's going on in the esophagus. So I think that a lot of this goes back to the choices that were made a long time ago in what is the right fundamental way to interfere with this type 2 allergic inflammation.

是的，我也認為這裡不能忽略機制。有許多說法稱，人們正在逐步揭示過敏性疾病的根本機制。如果某種方法對一種過敏性疾病有效，而對另一種過敏性疾病無效，那麼很難說你已經找到了過敏性疾病的根本機制。如果你只針對疾病的一部分，例如病情加重，而沒有影響肺功能，就很難說你已經觸及了過敏性疾病的根本原因。如果嗜酸性食道炎患者雖然可以降低嗜酸性粒細胞的數量，但卻無法改善食道實際發炎的症狀，那麼很難說他們觸及了疾病的根本原因。所以我認為這很大程度上要追溯到很久以前做出的選擇，即以正確的根本方式乾預這種 2 型過敏性發炎。

And I just want to add to that. As Len brings up a really good point, which is that part of our clinical development plan is actually to do studies where we show that in the same patients, we will be able to benefit multiple allergic conditions. And that is I think something that, if you know people who are suffering from any one of these severe allergic conditions, whether it's atopic dermatitis, for example, or severe asthma, they generally are suffering from other allergic conditions as well. And wouldn't it be wonderful if there was a drug that was essential driver of all of allergic disease that could benefit potentially all of the allergic manifestations of a single patient. So that is part of our clinical development plan going forward that we are going to be doing studies to actually be able to show that, hopefully. And we don't think there's any other current biologics out there that even have the opportunity to consider the possibility of doing those studies.

我只想補充一點。Len 提出了一個很好的觀點，那就是我們臨床開發計劃的一部分實際上是進行研究，以證明在同一組患者中，我們將能夠使多種過敏性疾病受益。我認為，如果你認識患有嚴重過敏性疾病的人，例如異位性皮膚炎或嚴重氣喘，他們通常也會患有其他過敏性疾病。如果有一種藥物能夠有效治療所有過敏性疾病，從而有可能改善單一患者的所有過敏症狀，那該有多好！所以，這是我們未來臨床開發計畫的一部分，我們將進行研究，以期最終能夠證明這一點。我們認為目前市面上還沒有其他生物製劑有機會考慮進行這些研究。

And our last question comes from Josh Schimmer from Evercore ISI.

最後一個問題來自 Evercore ISI 的 Josh Schimmer。

Just one on the IL-33 antibody. Can you elaborate on its positioning? What it brings to the table in addition to or instead of Dupixent? And is this a general area that you expect to further build pipeline?

只有一個關於IL-33抗體的研究。能詳細說明一下它的市場定位嗎？除了 Dupixent 之外，它還能帶來哪些好處？或者說，它能取代 Dupixent 帶來哪些好處？這是你們計劃進一步拓展業務的領域嗎？

Well, I think that, that's a great question. Thanks for bringing it up. And obviously, we didn't have enough time to really go into everything. But this is a really exciting target for us for many reasons. One of which is a lot of the biology that our group did to understand it. But just as much is that this is a recent success from our Regeneron Genetics Center. These large-scale sequencing efforts that we've undertaken to try to see how genetic variation is associated with disease. And IL-33 is one of the exciting premier targets that has been in our minds identified and validated by the genetics, not only in this disease, but in some other allergic diseases. So we've actually seen genetic evidence that gain-of-function mutations in IL-33. It increases the chances of having some of these disease loss-of-function mutations are protective. And that gets us a lot of confidence. We've always been driven by genetics. But in this case, it's using the latest large-scale genetics approaches to actually identify and validate targets that gives us this confidence to move this forward so rapidly. And the thing that's very exciting to us is this is an area where we already feel. We have made this advance and have this foundational treatment in dupilumab. And wouldn't it be great now, if we could improve the benefit in some patients by combining it with the IL-33. And once again, we're considering doing this in multiple allergic conditions because the genetic support that this can be the case, not only in asthma, but in COPD and maybe atopic dermatitis and other settings as well.

嗯，我覺得這是一個很好的問題。謝謝你提出這個問題。顯然，我們沒有足夠的時間深入探討所有內容。但出於諸多原因，這對我們來說是一個非常令人興奮的目標。其中之一是我們小組為了理解它而進行的大量生物學研究。但同樣重要的是，這是我們 Regeneron 遺傳學中心最近的成功。我們進行了這些大規模定序工作，試圖了解基因變異與疾病之間的關聯。IL-33 是我們認為透過遺傳學方法確定和驗證的一個令人興奮的首要靶點，不僅在這種疾病中，而且在其他一些過敏性疾病中也是如此。所以我們已經看到了IL-33功能獲得性突變的遺傳證據。它增加了患上某些疾病的幾率，但某些功能喪失突變具有保護作用。這給了我們很大的信心。我們一直以來都受基因驅動。但正是利用最新的大規模遺傳學方法來識別和驗證靶點，才使我們有信心如此迅速地推進這項研究。令我們非常興奮的是，我們已經對這個領域充滿熱情。我們已經取得了這一進展，並且擁有了度普利尤單抗這種基礎治療方法。如果現在我們能透過將其與 IL-33 結合使用來提高某些患者的療效，那該有多好。我們再次考慮在多種過敏性疾病中採用這種方法，因為有遺傳學證據表明，這種情況不僅可能發生在氣喘中，也可能發生在慢性阻塞性肺病、異位性皮膚炎和其他疾病中。

Right, let's just close one point that I think maybe we didn't emphasize enough is that the other thing that's really important about dupilumab is we really do have an extensive clinical development profile from the safety point of view. And that's building every day in the commercial point of view. And going forward in this field, Dupixent is now set an extremely high bar, I believe, not just on the efficacy side, but on the safety side. In the rheumatoid arthritis field, people, because biologics came with a cost, are willing to accept that cost because they had great efficacy. We've got really what I think is terrific efficacy. But also, almost unprecedented safety that we've seen thus far in our clinical trials. We really haven't seen the kinds of immune dysfunction problems that you see when you block other angles of the immune system.

好的，我們最後再補充一點，我認為我們可能沒有充分強調這一點，那就是dupilumab的另一個非常重要的特點是，從安全性的角度來看，我們確實擁有廣泛的臨床開發概況。從商業角度來看，這種情況每天都在加劇。展望未來，我認為，Dupixent 在這個領域已經樹立了極高的標準，不僅在療效方面，而且在安全性方面也是如此。在類風濕性關節炎領域，由於生物製劑價格昂貴，但療效顯著，人們願意接受這種價格。我認為我們確實取得了非常顯著的療效。但同時，這也是我們在臨床試驗中迄今所見過的幾乎前所未有的安全性。我們還沒有真正看到像阻斷免疫系統其他方面時那樣的免疫功能障礙問題。

And just to add to that, again, I mean, I think this is the future, the future of medicine and it's the future of drug development. The genetics that we have to support our targets, for example, IL-33. Not only are supporting that blocking IL-33 function or loss of function mutants in IL-33 can be protective, but they're also comforting us in terms of the safety profile going in. So genetics are really offering an opportunity to get insights before you ever do studies in humans into the future potential benefit, but also the safety profile, which is another reason why we're very excited about the IL-33.

我還要補充一點，我的意思是，我認為這就是未來，醫學的未來，也是藥物研發的未來。我們擁有支持我們目標的遺傳物質，例如 IL-33。不僅有研究支持阻斷 IL-33 功能或 IL-33 功能喪失突變體可以起到保護作用，這些研究也讓我們對安全性方面感到放心。因此，遺傳學確實提供了一個機會，讓我們在進行人體研究之前就能深入了解未來的潛在益處以及安全性，這也是我們對 IL-33 感到非常興奮的另一個原因。

Paulette, that concludes our call today.

Paulette，我們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, and 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，您現在可以斷開連接了。