雷傑納榮製藥 (REGN) 2017 Q2 法說會逐字稿

Welcome to the Regeneron Pharmaceuticals Q2 2017 Earnings Conference Call. My name is Jason, and I will be your operator. (Operator Instructions) Also please note, this conference is being recorded.

歡迎參加 Regeneron Pharmaceuticals 2017 年第二季財報電話會議。我叫傑森，我將是你的接線生。（操作說明）另請注意，本次會議正在錄音。

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

現在我將把電話轉給瑪妮莎·納拉辛漢。你可以開始了。

Thank you, Jason. Good morning, and welcome to Regeneron Pharmaceuticals' second quarter 2017 conference call. An archive of this webcast will be available on our website under Events and Presentations for 30 days.

謝謝你，傑森。早安，歡迎參加 Regeneron Pharmaceuticals 2017 年第二季電話會議。本次網路直播的存檔將在我們網站的「活動與演示」欄位下保留 30 天。

Joining me on the call today are Dr. Leonard Schleifer, Founder, President and CEO; Dr. George Yancopoulos, Founding Scientist, President and Chief Scientific Officer; Bob Terifay, Executive Vice President, Commercial; and Bob Landry, Chief Financial Officer.

今天與我一起參加電話會議的有：創辦人、總裁兼執行長 Leonard Schleifer 博士；創始科學家、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。

After our prepared remarks, we will open the call for Q&A. I would also like to remind you that remarks made on this call today include forward-looking statements about Regeneron. Such statements may include, but are not limited to those related to Regeneron and its products and businesses, sales and expense forecasts, financial forecasts, development programs and related anticipated milestones, collaborations, finances, regulatory matters, intellectual property, pending litigation and competition.

在我們發言完畢後，我們將開放問答環節。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。

Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in such statements. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, or SEC, including its Form 10-Q for the quarter ended June 30, 2017, which was filed with the SEC this morning.

每項前瞻性聲明都存在風險和不確定性，可能導致實際結果和事件與此類聲明中預測的結果和事件有重大差異。有關這些及其他重大風險的更完整描述，請參閱 Regeneron 向美國證券交易委員會 (SEC) 提交的文件，包括其截至 2017 年 6 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.

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。

We are aware that there is some technical issues with our externally hosted website, which we hope will be resolved shortly. Once our call concludes, Bob Landry and the IR team will be available to answer further questions.

我們注意到我們託管在外部的網站存在一些技術問題，希望這些問題能盡快解決。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. Good morning, everyone, and thank you for joining us on the call and webcast today. It has been an incredibly productive first half of the year for Regeneron with the launch of 2 important new medicines, and we are looking forward to continued progress in the second half of the year.

謝謝你，瑪妮莎。各位早安，感謝大家今天參加我們的電話會議和網路直播。今年上半年，Regeneron取得了令人矚目的豐碩成果，推出了兩款重要的新藥，我們期待在下半年繼續取得進展。

EYLEA, our flagship anti-VEGF drug for the treatment of a variety of retinal diseases, delivered strong results in both the U.S. and x U.S. markets. In the U.S., we experienced an 11% year-over-year growth in net sales during the quarter. We are proud that U.S. EYLEA net sales have grown steadily since our launch in 2011 without ever having taken any price increases. This growth has been driven by new patients and new indications.

EYLEA 是我們用於治療多種視網膜疾病的旗艦抗 VEGF 藥物，在美國和美國其他地區市場均取得了強勁的成績。在美國，本季淨銷售額年增 11%。我們很自豪，自 2011 年推出以來，美國 EYLEA 的淨銷售額一直穩定成長，從未漲價。這一增長是由新患者和新適應症推動的。

The launch of Dupixent, our breakthrough IL-4/IL-13 inhibitor for the treatment of moderate-to-severe atopic dermatitis is under way. Though it is still early, we are happy to report that the launch continues to progress extremely well, and most important, we have been very pleased with the positive reception that Dupixent has received from patients and physicians, along with the progress we have made with payers.

我們突破性的IL-4/IL-13抑制劑Dupixent，用於治療中重度異位性皮膚炎，其上市工作正在進行中。雖然現在還為時過早，但我們很高興地報告，Dupixent 的上市進展非常順利，最重要的是，我們對 Dupixent 受到患者和醫生的積極反響以及我們在與支付方合作方面取得的進展感到非常滿意。

In terms of the pace of the launch, we have seen a steady flow of both prescriptions written for new patients as well as prescriptions filled for new patients without any evidence of a bolus effect. We know from patients that atopic dermatitis can have a terrible impact on their lives, so we are glad that we are hearing positive anecdotes about how patients are responding to Dupixent in a manner consistent with the effect we saw in our clinical trials program.

就上市速度而言，我們看到新患者的處方數量和處方配藥量都在穩定增長，沒有任何跡象表明出現了衝擊效應。我們從患者那裡了解到，異位性皮膚炎會對他們的生活造成嚴重影響，因此我們很高興聽到有關患者對 Dupixent 的反應與我們在臨床試驗項目中看到的效果一致的積極軼事。

The teams at Regeneron and Sanofi have been working together to improve patient and physician awareness and ensure that those eligible for Dupixent are able to receive the drug. Bob Terifay will provide detailed metrics about this exciting launch. We are encouraged by the clinical progress that we are making with dupilumab and indications beyond atopic dermatitis. The most advanced of these is asthma, where we expect top line Phase III data from our second pivotal trial later this quarter, with a potential U.S. regulatory submission in the fourth quarter of this year. George will address the asthma indication in greater detail.

Regeneron 和 Sanofi 的團隊一直在共同努力，提高患者和醫生的意識，並確保符合 Dupixent 使用條件的患者能夠獲得該藥物。Bob Terifay 將提供有關此次令人興奮的發布會的詳細數據。我們對度普利尤單抗在臨床上的進展以及其在異位性皮膚炎以外的適應症感到鼓舞。其中進展最快的是氣喘，我們預計將在本季稍後公佈第二次關鍵性試驗的 III 期主要數據，並有可能在今年第四季向美國監管機構提交申請。喬治將更詳細地講解氣喘適應症。

In May, we received approval for and launched Kevzara, our IL-6 receptor antibody for the treatment of rheumatoid arthritis in the United States. Kevzara marks the sixth FDA approved drugs for Regeneron. We are proud that these 6 approved drugs, along with our pipeline of 17 product candidates, have all been discovered by the scientists at Regeneron. As you all know, it is rare for any biopharmaceutical company to bring a single drug all the way from discovery to commercialization. To have done it 6 times is a tribute to our people and their efforts. Regeneron-discovered drugs had over $1.5 billion in global net sales in the second quarter of 2017.

今年 5 月，我們的 IL-6 受體抗體 Kevzara 獲得批准並在美國上市，用於治療類風濕性關節炎。Kevzara是Regeneron公司第六款獲得FDA批准的藥物。我們很自豪，這 6 種已獲批准的藥物，以及我們正在研發的 17 種候選產品，都是由 Regeneron 的科學家發現的。眾所周知，生物製藥公司很少能將一種藥物從發現到商業化全程推進。六次奪冠是對我們人民及其努力的最佳讚美。2017 年第二季度，再生元公司研發的藥物全球淨銷售額超過 15 億美元。

Turning now to PRALUENT. We are awaiting the opinion of the U.S. Court of Appeals for the Federal Circuit found in the oral arguments that occurred in early June. We continue to believe that the law and facts support our position. Our 18,000-patient cardiovascular outcome study is ongoing, and we expect to report data from this study in early 2018. We and our collaborator, Sanofi, are committed to optimizing the potential benefit that this important drug can bring to patients.

現在轉向 PRALUENT。我們正在等待美國聯邦巡迴上訴法院對 6 月初舉行的口頭辯論作出的意見。我們仍然認為法律和事實支持我們的立場。我們正在進行一項針對 18,000 名患者的心血管結局研究，預計將於 2018 年初公佈該研究的數據。我們和我們的合作夥伴賽諾菲致力於最大限度地發揮這種重要藥物對患者的潛在益處。

Our immuno-oncology programs continue to advance. At the June Annual ASCO meeting, we presented positive clinical data from our PD-1 antibody program in cutaneous squamous cell carcinoma. George will provide additional details on these data, as well as the progress we are making with our other immuno-oncology programs.

我們的免疫腫瘤學課程持續取得進展。在 6 月的 ASCO 年會上，我們展示了 PD-1 抗體計畫在皮膚鱗狀細胞癌治療中取得的積極臨床數據。George 將提供有關這些數據的更多細節，以及我們在其他免疫腫瘤學課程中取得的進展。

We are preparing for a busy second half, with multiple important data readouts and continued pipeline progress. You'll hear more about that -- some of these programs from George. With that, I'd like to turn the call over to George.

我們正在為繁忙的下半年做準備，屆時將有多項重要數據公佈，並且研發管線也將持續推進。你會聽到更多關於這方面的消息——喬治的一些節目。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 today. We believe Regeneron is a very different type of company in that it was founded by and is led by physicians and scientists dedicated to a science-first approach to bringing new medicines that can make important difference in patients' lives. This commitment, supported by a talented and longstanding team of scientists and strategic investments in internal technology development, has today produced what many believe is one of the best pipelines in the industry. And as Len mentioned, all of our approved and investigational therapies were discovered in our own labs by our own people.

謝謝Len，也祝今天到場的各位早安。我們認為 Regeneron 是一家非常不同的公司，因為它是由醫生和科學家創立並領導的，他們致力於以科學為先導，研發能夠對患者生活產生重大影響的新藥。這項承諾，加上一支才華橫溢、經驗豐富的科學家團隊以及對內部技術開發的策略性投資，如今已打造出許多人認為業內最好的研發管線之一。正如 Len 所提到的，我們所有已獲批准和正在研究的療法都是由我們自己的人員在我們自己的實驗室中發現的。

I will provide a general update in our R&D progress today and highlight 2 Phase III programs for which we expect to have data readouts in the second half of this year. These are dupilumab in asthma and Regeneron 2810, our PD-1 antibody in cutaneous squamous cell carcinoma.

今天我將總體報告我們的研發進展，並重點介紹兩個預計在今年下半年獲得數據讀數的 III 期項目。這些藥物分別是用於治療氣喘的度普利尤單抗和用於治療皮膚鱗狀細胞癌的 PD-1 抗體 Regeneron 2810。

I'd like to begin with one of our most exciting late-stage programs. Dupixent, also known as dupilumab, our interleukin-4 and interleukin-13 blocker, which was approved in March by the FDA for the treatment of moderate-to-severe atopic dermatitis in adult patients whose disease is not adequately controlled with topical prescription therapy or when therapies are not advisable.

我想先介紹我們最令人興奮的後製研發項目之一。Dupixent，又稱 dupilumab，是一種白細胞介素-4 和白細胞介素-13 阻斷劑，於 3 月獲得 FDA 批准，用於治療成人中度至重度異位性皮膚炎，適用於局部處方治療無法充分控制病情或不宜進行其他治療的患者。

In addition to the FDA approval, we were recently granted a positive opinion by the European Medicines Agency's Committee for medicinal products for human use, or the CHMP, for the treatment of moderate-to-severe atopic dermatitis in adults who are candidates for systemic therapy. We expect to receive EU approval in the third quarter of 2017. In the pediatric atopic dermatitis setting, we are currently enrolling a Phase III study of dupilumab in patients 12 to 17 years of age. In the second half of the year, we expect to initiate 2 additional studies in the younger atopic dermatitis patients, the first in children between the ages of 6 and 11 and the second children between the ages of 6 months and 5 years.

除了獲得 FDA 的批准外，我們最近還獲得了歐洲藥品管理局人用藥品委員會 (CHMP) 的積極意見，用於治療適合接受全身治療的中度至重度成人異位性皮膚炎。我們預計將於 2017 年第三季獲得歐盟批准。在兒童異位性皮膚炎領域，我們目前正在招募 12 至 17 歲的患者參與度普利尤單抗的 III 期研究。今年下半年，我們計劃針對年輕的異位性皮膚炎患者進行兩項額外的研究，第一項研究對象為 6 至 11 歲的兒童，第二項研究對象為 6 個月至 5 歲的兒童。

We believe that dupilumab has potential to benefit a variety of allergic or atopic conditions, and we are investigating the use of dupilumab in several of these, including asthma, eosinophilic esophagitis and nasal polyps. Today, I'd like to focus on the potential opportunity in our most advanced indication, asthma, where we expect top line data later this quarter from our pivotal Phase III study, LIBERTY ASTHMA QUEST.

我們相信度普利尤單抗有潛力使多種過敏或特異性疾病受益，我們正在研究度普利尤單抗在幾種此類疾病中的應用，包括氣喘、嗜酸性食道炎和鼻息肉。今天，我想重點談談我們在最先進的適應症——氣喘——方面的潛在機會。我們預計將在本季稍後公佈關鍵性 III 期研究 LIBERTY ASTHMA QUEST 的主要數據。

Data from our previously reported positive Phase II study are considered pivotal and will support our regular submission, which we anticipate in the fourth quarter of 2017. The Phase III LIBERTY ASTHMA QUEST study enrolled approximately 1,800 adult and adolescent patients with persistent uncontrolled asthma. In this study, patients were randomized to one of 2 dupilumab arms, 200 milligrams every other week or 300 milligrams every other week or placebo. Patients who are on background therapy of medium-to-high dose inhaled corticosteroids, plus a second controller medications, such as a long-acting beta agonist or a leukotriene receptor antagonist. The study has 2 primary endpoints. The annualized rate of asthma attacks or exacerbations over the 52-week treatment period and the absolute change from baseline in FEV1 at week 12, a measure of lung function, both of which will be assessed in the overall patient population.

我們先前報告的積極的 II 期研究數據被認為是關鍵性的，並將支持我們的常規提交，我們預計將在 2017 年第四季度提交。LIBERTY ASTHMA QUEST III 期研究招募了約 1800 名患有持續性未控制氣喘的成人和青少年患者。在這項研究中，患者被隨機分配到 2 個 dupilumab 治療組之一，每兩週接受 200 毫克或每兩週接受 300 毫克治療，或接受安慰劑治療。正在接受中高劑量吸入性皮質類固醇背景治療的患者，以及接受第二種控制藥物治療的患者，例如長效β受體激動劑或白三烯受體拮抗劑。該研究有兩個主要終點。在 52 週的治療期內，氣喘發作或加重的年化發生率以及第 12 週 FEV1 相對於基線的絕對變化（肺功能指標）都將在整體患者群體中進行評估。

I'd like to remind you of data from our previously reported positive Phase IIb study, which was conducted in a patient population similar to the one we are studying in Phase III. This Phase IIb study randomized 769 patients with moderate-to-severe asthma who are uncontrolled despite treatment with inhaled corticosteroids and long-acting beta agonist. The results from this study demonstrate that dupilumab administered at 200 milligrams every other week or 300 milligrams every other week, in combination with standard of care therapy, demonstrated a significant 12% to 15% improvement in FEV1 at week 12 over the standard of care alone, as well as a significant 64% to 75% reduction in exacerbations over standard of care alone. Importantly, these positive responses were seen in both the patient population with high blood eosinophils believed to be a marker of the allergic disease patients, as well as the overall study population. The most common adverse event in the study was injection site reaction, which was more frequent in the dupilumab dose group at 13% to 25% compared to 12% in the placebo group. The incidence of infections was balanced across treatment groups, as was the incidence of serious adverse events. We believe that if the Phase III LIBERTY ASTHMA QUEST data demonstrate efficacy, both in terms of reduction and exacerbations and an improvement in lung function in all comers, including the subset of patients with high eosinophil count, as well as the subset of patients with low eosinophil counts, it will be an important differentiating factor. No approved biologic has demonstrated robust improvement in lung function, as well as profound reduction in exacerbations in the overall asthma population, including both these important subsets of patients.

我想提醒各位注意我們先前報告的積極的 IIb 期研究的數據，該研究是在與我們正在 III 期研究中的患者群體相似的患者群體中進行的。這項 IIb 期研究隨機納入了 769 名中度至重度氣喘患者，這些患者儘管接受了吸入性皮質類固醇和長效β受體激動劑治療，但氣喘仍未得到控制。這項研究的結果表明，每兩週給予 200 毫克或 300 毫克度普利尤單抗，並結合標準治療，在第 12 週時，FEV1 較單獨使用標準治療顯著改善了 12% 至 15%，並且與單獨使用標準治療相比，病情加重次數顯著減少了 64% 至 75%。重要的是，在血液嗜酸性粒細胞水平高的患者群體（被認為是過敏性疾病患者的標誌）以及整個研究人群中都觀察到了這些積極的反應。研究中最常見的不良事件是注射部位反應，在度普利尤單抗劑量組發生率較高，為 13% 至 25%，安慰劑組為 12%。各治療組的感染發生率較為均衡，且嚴重不良事件的發生率也較為均衡。我們相信，如果 LIBERTY ASTHMA QUEST III 期數據能夠證明其療效，無論是在減少和緩解氣喘發作方面，還是在所有患者（包括嗜酸性粒細胞計數高的患者亞組和嗜酸性粒細胞計數低的患者亞組）的肺功能方面，它都將是一個重要的區分因素。目前尚無核准的生物製劑能夠顯著改善肺功能，並大幅減少包括這兩個重要患者亞群在內的所有氣喘患者的病情加重次數。

In addition to the LIBERTY ASTHMA QUEST study, we are also conducting another Phase III study, LIBERTY ASTHMA VENTURE, which is designed to determine the efficacy and safety of dupilumab, while reducing the use of oral corticosteroids in patients with severe oral steroid-dependent asthma. Top line results from this study will be reported by the end of 2017, and are anticipated to be part of our regulatory submission. We are also investigating the use of dupilumab in younger patients with asthma with an ongoing Phase III study in children ages 6 to 11 years old.

除了 LIBERTY ASTHMA QUEST 研究之外，我們還在進行另一項 III 期研究 LIBERTY ASTHMA VENTURE，旨在確定度普利尤單抗的療效和安全性，同時減少重度口服類固醇依賴性氣喘患者對口服皮質類固醇的使用。這項研究的主要結果將於 2017 年底公佈，預計將成為我們監管申報的一部分。我們目前也正在研究度普利尤單抗在年輕氣喘患者中的應用，正在進行一項針對 6 至 11 歲兒童的 III 期研究。

Turning now to other potential and important indications where we are investigating dupilumab. We currently have 2 Phase III studies ongoing in patients with nasal polyps. We're also planning a Phase III study in patients with eosinophilic esophagitis, following recent positive results from a Phase II proof-of-concept study. These results will be presented in detail at an upcoming medical conference.

現在讓我們來看看我們正在研究 dupilumab 的其他潛在和重要適應症。我們目前正在進行兩項針對鼻息肉患者的 III 期研究。繼近期 II 期概念驗證研究取得正面結果後，我們也計劃針對嗜酸性食道炎患者進行 III 期研究。這些研究結果將在即將召開的醫學會議上詳細發表。

We're also planning studies of dupilumab in patients with food allergies. According to data from the Centers for Disease Control, or the CDC, allergic diseases are the sixth leading cause of chronic illness in the United States and have reached epidemic proportions. There is a tremendous amount of scientific debate on the drivers behind this increased incidence and prevalence. Our collective data from the dupilumab clinical studies suggest that deviation of the immune system, triggered by overactivity of the IL-4/IL-13 access may be the key driver of many, if not, most allergic conditions. So-called allergic patients with an overactive IL-4/IL-13 pathway often suffer for more than one manifestation at a given time. For example, patients with asthma or atopic dermatitis often also suffer from severe respiratory or food allergies, and the combination of multiple allergic conditions can be quite devastating for an allergic individual. The possibility that a single biologic may simultaneous help many of these related allergic conditions would be very exciting and important to many patients.

我們也計劃進行度普利尤單抗治療食物過敏患者的研究。根據美國疾病管制與預防中心（CDC）的數據，過敏性疾病是美國第六大慢性病，並且已經達到流行病的程度。關於導致發病率和盛行率上升的驅動因素，目前存在大量的科學爭論。我們從度普利尤單抗臨床研究中收集的數據表明，由IL-4/IL-13通路過度活躍引發的免疫系統偏離可能是許多（如果不是大多數）過敏性疾病的關鍵驅動因素。所謂過敏患者，其IL-4/IL-13路徑過度活躍，通常會同時出現多種症狀。例如，患有氣喘或異位性皮膚炎的患者通常也會患有嚴重的呼吸道或食物過敏，多種過敏症的疊加對過敏體質的人來說可能是毀滅性的。如果一種生物製劑能夠同時幫助治療多種相關的過敏性疾病，那麼這對許多患者來說將是一件非常令人興奮且重要的事情。

Just as important, it would be ideal if such a correction of allergic disease could occur without inducing concurrent immunosuppression. All our studies to date indicate that unlike many other biologics that target the immune system, which often produces immunosuppression and side effects, such as infections, dupilumab does not appear to be an immunosuppressant. Rather, dupilumab appears to be an immunomodulatory agent that blocks the pathologic overactivity of IL-4/IL-13-driven allergic responses.

同樣重要的是，如果能在不引起免疫抑制的情況下矯正過敏性疾病，那就再理想不過了。我們迄今為止的所有研究表明，與許多其他針對免疫系統的生物製劑（通常會產生免疫抑制和感染等副作用）不同，度普利尤單抗似乎不是一種免疫抑制劑。相反，dupilumab 似乎是一種免疫調節劑，可以阻斷 IL-4/IL-13 驅動的過敏反應的病理性過度活躍。

I would now like to talk about another important area of research for us at Regeneron, and that is the field of immuno-oncology. Despite all the early successes and excitement in the field, cancer remains a challenging area, and there have been a recent string of disappointments, with several development programs. Just last week, another highly anticipated trial exploring the PD-L1 antibody alone, and in combination with the CTLA-4 antibody yielded disappointing data. These developments underscore that the field is still in the very early stages of fully understanding how to exploit and optimize the power of immuno-oncology.

現在我想談談Regeneron的另一個重要研究領域，那就是免疫腫瘤學領域。儘管癌症治療領域早期取得了許多成功，令人振奮，但癌症仍然是一個充滿挑戰的領域，而且最近幾個研發項目也遭遇了一系列令人失望的進展。就在上週，另一項備受期待的試驗探索了 PD-L1 抗體單獨使用以及與 CTLA-4 抗體聯合使用的效果，結果令人失望。這些進展表明，該領域仍處於充分了解如何利用和優化免疫腫瘤學力量的非常早期的階段。

In contrast to some of the recent disappointing results elsewhere, recent developments with our PD-1 antibody have been positive. The ASCO Conference in June this year was an exciting time for us. We presented important data with Regeneron 2810, our PD-1 antibody in cutaneous squamous cell carcinoma, or CSCC, which is the second most common skin cancer after basal cell carcinoma and the second deadliest skin cancer after melanoma. It is estimated that there are approximately 4,000 to 8,000 deaths annually in the United States from CSCC.

與近期其他地方一些令人失望的結果相反，我們PD-1抗體的最新進展是正面的。今年六月的ASCO會議對我們來說是一段令人興奮的時光。我們展示了 Regeneron 2810（一種 PD-1 抗體）在皮膚鱗狀細胞癌 (CSCC) 中的重要數據。 CSCC 是繼基底細胞癌之後第二常見的皮膚癌，也是繼黑色素瘤之後第二致命的皮膚癌。據估計，美國每年約有 4,000 至 8,000 人死於 CSCC。

For patients with advanced CSCC, there are limited treatment options and no standard of care. The data that we presented at the ASCO Conference were the pooled results from 2 expansion arms in metastatic or inoperable locally or regionally advanced CSCC from 26 patients in our 392-patient Phase I trial. These CSCC data demonstrated that treatment with Regeneron 2810 led to an overall response rate of 46%, including 2 complete responses, according to investigators' assessments, in a disease control rate of 69%. The median progression free and overall survival were not reached at the data cut off date, with the median follow-up of 6.9 months. The adverse event profile was generally consistent with agents in this class. Based on these encouraging results, we are conducting larger efforts in metastatic and locally advanced cutaneous squamous cell carcinoma. Recent discussions with the FDA indicate that if these data are robust, they could form the basis of our regulatory submission in the first quarter of 2018. Work on developing Regeneron 2810 and other indications continues, where we are currently enrolling a Phase III study in our non-small cell lung cancer indication, a Phase II study in basal cell carcinoma, and additional earlier studies in other indications as well. We are also exploring the use of our PD-1 antibody in combination with novel vaccines and oncolytic viruses.

對於晚期皮膚鱗狀細胞癌患者，治療選擇有限，也沒有標準治療方案。我們在 ASCO 會議上展示的數據是來自我們 392 名患者的 I 期試驗中 26 名轉移性或無法手術的局部或區域晚期 CSCC 患者的 2 個擴展組的匯總結果。根據研究人員的評估，這些 CSCC 數據表明，使用 Regeneron 2810 治療的總緩解率為 46%，其中包括 2 例完全緩解，疾病控制率為 69%。截至資料截止日期，中位無惡化存活期和總存活期均未達到，中位追蹤時間為 6.9 個月。不良事件狀況大致上與同類藥物一致。基於這些令人鼓舞的結果，我們正在對轉移性和局部晚期皮膚鱗狀細胞癌進行更大規模的研究。最近與 FDA 的討論表明，如果這些數據可靠，它們可以作為我們在 2018 年第一季向監管機構提交申請的基礎。Regeneron 2810 和其他適應症的開發工作仍在繼續，我們目前正在進行針對非小細胞肺癌適應症的 III 期研究、針對基底細胞癌的 II 期研究，以及其他適應症的早期研究。我們也正在探索將我們的 PD-1 抗體與新型疫苗和溶瘤病毒合併使用。

Our second checkpoint inhibitor, Regeneron 3767, an antibody LAG3, is currently enrolling patients in 2 studies, one in monotherapy and one in combination with our PD-1 antibody. Additionally, our bispecific CD20 CD3 antibody, Regeneron 1979, is also being studied in the clinic as both a monotherapy and in combination with our PD-1 antibody. In the second quarter, we were granted orphan drug designation from the FDA for Regeneron 1979 for the treatment of diffuse large b-cell lymphoma, or DLBCL.

我們的第二個檢查點抑制劑 Regeneron 3767，一種 LAG3 抗體，目前正在招募患者參與兩項研究，一項是單藥治療，另一項是與我們的 PD-1 抗體聯合治療。此外，我們的雙特異性 CD20 CD3 抗體 Regeneron 1979 也正在臨床上進行研究，既可以作為單藥療法，也可以與我們的 PD-1 抗體聯合使用。第二季度，我們的 Regeneron 1979 獲得了 FDA 授予的孤兒藥資格，用於治療瀰漫性大 B 細胞淋巴瘤 (DLBCL)。

Our EYLEA business continues to be strong and we remain committed to maintaining our leadership position. Part of this commitment is to help educate the community on the importance of regular dosing with anti-VEGF therapies. Real-world evidence indicates that many patients receiving anti-VEGF therapies are not being optimally treated, resulting in more widespread vision loss than is necessary. This decreases patients quality of life, and results in substantial costs to society, particularly when leading to blindness and disability. There has even been a bias that chronic sustained VEGF inhibition may account for the inability of most patients to maintain their vision over the long term.

我們的安樂業務依然強勁，我們將繼續致力於保持領先地位。這項承諾的一部分是幫助教育社區了解定期服用抗 VEGF 療法的重要性。現實世界的證據表明，許多接受抗 VEGF 療法的患者沒有得到最佳治療，導致視力喪失的範圍比必要的更廣。這會降低患者的生活質量，並對社會造成巨大的經濟損失，尤其是在導致失明和殘疾的情況下。甚至有人認為，長期持續的 VEGF 抑制可能是導致大多數患者無法長期維持視力的原因。

Our long-term data with the VIEW Extension Study, which followed wet AMD patients treated for approximately 4 years using EYLEA in a standardized and fixed regimen, showed that for the first time, the initial gains seen with any anti-VEGF agents can be largely maintained for the long term. This was the first time that such data have been demonstrated with any anti-VEGF agents. This is in contrast to long-term studies with other anti-VEGF agents, using flexible dosing regiments, such as the CAT study, which resulted in loss of the early visual acuity gains that were achieved with monthly dosing. Taken together with additional real-world data, this suggested under-treatment with anti-VEGF agent is a serious disservice to patients and a major public health issue. We believe the overall data in this field indicates that the treatment goal of anti-VEGF therapy should be chronic, sustained and potent VEGF inhibition. Many elderly people are needlessly losing vision and going blind. We are committed to doing a better job to address this issue.

我們透過 VIEW 擴展研究獲得的長期數據顯示，使用 EYLEA 按照標準化的固定方案治療濕性 AMD 患者約 4 年，結果表明，首次使用任何抗 VEGF 藥物所獲得的初始療效都可以在很大程度上長期維持。這是首次使用抗 VEGF 藥物獲得此類數據。這與使用彈性給藥方案的其他抗 VEGF 藥物的長期研究（例如 CAT 研究）形成對比，後者導致每月給藥所獲得的早期視力改善效果喪失。結合其他真實世界數據，這種抗 VEGF 藥物治療不足的情況，對患者來說是嚴重的傷害，也是一個重大的公共衛生問題。我們認為該領域的總體數據表明，抗 VEGF 療法的治療目標應該是長期、持續且強效的 VEGF 抑制。許多老年人正在無謂地喪失視力，最終失明。我們致力於更好地解決這個問題。

In the second half of this year, we expect to report top line data from 2 Phase II studies, one in wet age-related macro degeneration, or wet AMD, and another in diabetic macular edema, or DME, of EYLEA in combination with nesvacumab, an antibody to angiopoietin-2. The primary endpoint in these studies will be assessed at 36 weeks, and we expect top line results from these studies in the fourth quarter of 2017. These results will help us understand where the combination of EYLEA with an antibody to angiopoietin-2 can improve upon the already high bar that has been set by EYLEA.

今年下半年，我們預計將發表 2 項 II 期研究的主要數據，一項是針對濕性老年性大變性（濕性 AMD），另一項是針對糖尿病性黃斑水腫（DME），研究對象為 EYLEA 與抗血管生成素-2 抗體 nesvacumab 聯合用藥。這些研究的主要終點將在 36 週時進行評估，我們預計將在 2017 年第四季獲得這些研究的主要結果。這些結果將幫助我們了解 EYLEA 與抗血管生成素-2 抗體的結合能在 EYLEA 已經設定的高標準之上取得怎樣的進展。

Panorama, our Phase III study of EYLEA in patients with non-proliferative diabetic retinopathy without diabetic (inaudible), continues to enroll patients. The primary endpoints of this study will be assessed at week 24 and at week 52. A separate Phase III study in this syndication, 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. We plan to submit our supplemental BLA for EYLEA dose every 12 weeks by the end of the year.

Panorama 是我們正在進行的針對非增殖性糖尿病視網膜病變患者（無糖尿病）的 EYLEA III 期研究，目前仍在招募患者。本研究的主要終點將在第 24 週和第 52 週進行評估。此聯合研究方案中的另一項 III 期研究（Protocol-W）由糖尿病視網膜病變臨床研究網絡（DRCR）開展，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。我們計劃在年底前提交每 12 週一次的 EYLEA 補充生物製品許可申請 (BLA)。

Moving on to PRALUENT, our PCSK9 inhibitor antibody for lowering LDL cholesterol. We expect in the first quarter of 2018 top line data from the ongoing 18,000-patient ODYSSEY OUTCOMES study. If these results are positive and recognized in formal treatment guidelines, we believe this would allow for greater uptake of drugs in this important class. In addition to our efforts with PRALUENT in cardiovascular disease, we are also developing evinacumab, our antibody to angiopoietin-like 3, for the treatment of homozygous familial hypercholesterolemia or homozygous FH, a severe forms of hyperlipidemia. Following positive data from a Phase II proof-of-concept study in patients with homozygous FH, we plan to advance evinacumab into a Phase III trial in homozygous FH.

接下來是 PRALUENT，我們用來降低 LDL 膽固醇的 PCSK9 抑制劑抗體。我們預計將在 2018 年第一季獲得正在進行的 18,000 名患者的 ODYSSEY OUTCOMES 研究的主要數據。如果這些結果是正面的，並且被正式的治療指南所認可，我們相信這將使這類重要藥物得到更廣泛的應用。除了我們在心血管疾病領域與 PRALUENT 開展合作外，我們還在開發 evinacumab，這是一種針對血管生成素樣 3 的抗體，用於治療純合子家族性高膽固醇血症或純合子 FH，這是一種嚴重的血脂異常。在針對純合子家族性高膽固醇血症 (FH) 患者的 II 期概念驗證研究中獲得積極數據後，我們計劃將 evinacumab 推進到針對純合子 FH 的 III 期試驗中。

Additional studies in hypertriglyceridemia and heterozygous familial hypercholesterolemia are also being planned. As a reminder, evinacumab has been granted both orphan drug as well as breakthrough designation by the FDA for the treatment of homozygous FH. In May of this year, we published data in the New England Journal of Medicine showing that people with inactivating mutations of angiopoietin-like 3 have an approximately 40% reduced risk of coronary artery disease, and significantly lower levels of key blood lipids, including triglycerides and LDL cholesterol. We were able to identify these mutations through our genetics efforts at the Regeneron Genetics Center. Furthermore, we published Phase II clinical data that demonstrated blocking angiopoietin-like 3 with evinacumab in patients with homozygous FH, who were on lipid lowering therapy, resulting in an additional 49% reduction from base line in LDL cholesterol at week 4. A reduction in other key lipid parameters, including Lp(a) and triglycerides, was also observed.

針對高三酸甘油脂血症和雜合子家族性高膽固醇血症的更多研究也在計畫中。提醒大家，evinacumab 已被 FDA 授予孤兒藥資格和突破性療法資格，用於治療純合子 FH。今年 5 月，我們在《新英格蘭醫學雜誌》上發表了數據，顯示血管生成素樣 3 失活突變的人患冠狀動脈疾病的風險降低了約 40%，並且關鍵血脂（包括三酸甘油酯和低密度脂蛋白膽固醇）的水平顯著降低。我們透過在 Regeneron 遺傳學中心進行的遺傳學研究，發現了這些突變。此外，我們公佈了 II 期臨床數據，證明在接受降血脂治療的純合子家族性高膽固醇血症 (FH) 患者中，使用 evinacumab 阻斷血管生成素樣 3，可使 LDL 膽固醇在第 4 週比基線水平額外降低 49%。同時也觀察到其他關鍵脂質參數（包括 Lp(a) 和三酸甘油酯）的降低。

Kevzara, or sarilumab, our interleukin-6 receptor antibody for rheumatoid arthritis, has received regulatory approval in Canada, the United States and the EU. In terms of clinical development for sarilumab, we are currently enrolling patients in a Phase II study in polyarticular course juvenile idiopathic arthritis, or pJIA. We are also advancing our Phase III program for fasinumab, our nerve growth factor antibody for pain, where we dose the first patient or our Phase III efficacy study in osteoarthritis pain. We remain on track to initiate a Phase III efficacy study in chronic lower back pain in the second half, and we continue to enroll our long-term safety study.

Kevzara（或稱 sarilumab）是我們用於治療類風濕性關節炎的白血球介素-6 受體抗體，已在加拿大、美國和歐盟獲得監管部門批准。就 sarilumab 的臨床開發而言，我們目前正在招募患者參與一項針對多關節型幼年特發性關節炎 (pJIA) 的 II 期研究。我們也正在推進針對神經生長因子抗體 fasinumab（用於治療疼痛）的 III 期臨床試驗項目，我們將對首位患者進行給藥，或進行針對骨關節炎疼痛的 III 期療效研究。我們仍按計畫在下半年啟動針對慢性腰痛的 III 期療效研究，並繼續招募長期安全性研究的受試者。

In the second half of the year, we expect to report top line data from our Phase III program with Regeneron 2222, also known as suptavumab, a wholly-owned antibody that we are investigating for prophylactics of respiratory syncytial virus or RSV. RSV infections represent a substantial burden, and it's estimated that over 20% of infants under the age of 6 months require medical attention for RSV annually. This study explores 2 dosing regimens, suptavumab administered either once or twice during the RSV season in preterm infants.

今年下半年，我們預計將公佈 Regeneron 2222（也稱為 suptavumab）的 III 期計畫的初步數據。 Suptavumab 是一種我們完全擁有的抗體，我們正在研究它用於預防呼吸道合胞病毒 (RSV)。RSV 感染造成了相當大的負擔，據估計，每年有超過 20% 的 6 個月以下嬰兒需要因 RSV 接受治療。本研究探討了兩種給藥方案，即在 RSV 流行季節對早產兒使用 suptavumab 一次或兩次。

Development in other parts of our early stage pipeline continue to advance, and I would like to highlight a few of the programs. Our Activin A antibody, Regeneron 2477, is in clinical development for the treatment of the rare disease, Fibrodysplasia Ossificans Progressiva, or FOP. In the second quarter of 2017, we received Fast Track designation from the FDA, and we anticipate initiating a Phase II clinical study in the second half of 2017. We're also studying our Activin A antibody in combination with our GDF8 antibody in settings where there may be a benefit to promoting muscle growth. Regeneron 3500, our interleukin 33 antibody, is in Phase I clinical studies in patients with asthma; and Regeneron 3918, our wholly-owned C5 antibody, has now entered clinical development.

我們早期研發管線其他部分的進展也在持續推進，我想重點介紹其中幾個項目。我們的 Activin A 抗體 Regeneron 2477 正在進行臨床開發，用於治療罕見疾病進行性骨化性纖維發育不良症 (FOP)。2017 年第二季度，我們獲得了 FDA 的快速通道資格，預計將於 2017 年下半年啟動 II 期臨床研究。我們也正在研究將我們的 Activin A 抗體與 GDF8 抗體合併使用，以期在可能促進肌肉生長的情況下獲得益處。我們的白細胞介素 33 抗體 Regeneron 3500 正在進行氣喘患者的 I 期臨床研究；而我們全資擁有的 C5 抗體 Regeneron 3918 現已進入臨床開發階段。

Before I conclude, I want to say a few words about the ending of our antibody discovery agreement with Sanofi, which Bob Landry will discuss in more detail, PRALUENT; Dupixent, Kevzara; REGN2810, or our anti-PD-1 antibody; Regeneron 3500, or anti-IL 33 antibody; and Regeneron 3767, our anti 3 LAG3 antibody, were all discovered and initially developed under this antibody discovery agreement. PRALUENT, Dupixent, Kevzara and Regeneron 3500 will continue to be developed and commercialized, as applicable, with Sanofi under the antibody License and Collaboration Agreement. Regeneron 2810 and Regeneron 3767 will continue to be developed with Sanofi under the immuno-oncology collaboration. We believe that our collaboration with Sanofi is one of the most productive arrangements in the history of the biotechnology industry, and we look forward to continued collaborative efforts with Sanofi in the future.

在結束之前，我想簡單談談我們與賽諾菲的抗體發現協議的終止，鮑勃·蘭德里將對此進行更詳細的討論。 PRALUENT；Dupixent，Kevzara；REGN2810，即我們的抗PD-1抗體；Regeneron 3500，即抗IL-33抗體；以及Regeneron 3767，即我們的抗3LAG3抗體，都是根據這項抗體發現協議發現並最初開發的。PRALUENT、Dupixent、Kevzara 和 Regeneron 3500 將繼續根據抗體許可和合作協議與賽諾菲進行開發和商業化（如適用）。Regeneron 2810 和 Regeneron 3767 將繼續與賽諾菲在免疫腫瘤學合作框架下進行開發。我們相信，與賽諾菲的合作是生技產業史上最有成效的合作安排之一，我們期待未來與賽諾菲繼續合作。

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

接下來，我將把電話交給鮑伯·特里費。

Thank you, George, and good morning, everyone. EYLEA continues to be the market-leading product among FDA approved anti-VEGF agents for all of its approved indications in the United States, with a 73% market share in terms of dollars in the second quarter of 2017 compared to 69% market share in the second quarter of 2016. In the second quarter of 2017, U.S. net sales of EYLEA, or aflibercept, were $919 million versus $831 million in the second quarter of 2016, which represents growth of 11% year-over-year. Ex-U. S., net sales of EYLEA in the second quarter of 2017 were $542 million compared to $486 million in the second quarter of 2016, which represents growth of 12% on a reported basis.

謝謝你，喬治，大家早安。在美國，EYLEA 仍然是 FDA 批准的抗 VEGF 藥物中所有核准適應症的市場領先產品，2017 年第二季市佔率（以美元計）為 73%，而 2016 年第二季市佔率為 69%。2017 年第二季度，EYLEA（阿柏西普）在美國的淨銷售額為 9.19 億美元，而 2016 年第二季為 8.31 億美元，年增 11%。前美國據報告，EYLEA 2017 年第二季淨銷售額為 5.42 億美元，而 2016 年第二季為 4.86 億美元，按報告數據計算增加了 12%。

For the second 6 months ended June 30, 2017, U.S. EYLEA net sales grew 10% year-over-year compared to the first half of 2016. The overall branded anti-VEGF market in the U.S. grew by 7.4% in the first half of 2017 compared to the first half of 2016. These numbers indicate that EYLEA growth is driven by overall growth in the market, as well as an increase in market share. As George noted, we are preparing for the submission this year of data to the FDA from the second year of our Phase III wet AMD studies, which showed that approximately 50% of patients were able to be treated with every 12-week dosing. We are also continuing to enroll patients in a Phase III study in nonproliferative diabetic retinopathy.

截至 2017 年 6 月 30 日的下半年，美國安禮 (EYLEA) 淨銷售額較 2016 年上半年年增 10%。2017 年上半年，美國品牌抗 VEGF 市場整體成長了 7.4%，而 2016 年上半年則沒有成長。這些數字表明，安永的成長是由市場整體成長以及市場份額的增加所驅動的。正如喬治所指出的，我們正在準備今年向 FDA 提交我們 III 期濕性 AMD 研究第二年的數據，該研究表明，大約 50% 的患者能夠接受每 12 週一次的給藥治療。我們也將繼續招募患者參與非增殖性糖尿病視網膜病變的 III 期研究。

Turning now to the recent launch of Dupixent, or dupilumab, in the U.S. for the treatment of adult patients with moderate-to-severe atopic dermatitis. As reported by our collaborator, Sanofi, global net sales for Dupixent in the second quarter were $29 million. These sales largely reflect end-user demand in the United States, with negligible contribution from inventory build. We are pleased with the way the launch is tracking, and the prescriptions are trending ahead of other recently launched Biologics in dermatology. As of last week, over 5,000 health care professionals had prescribed Dupixent, with over 13,000 prescriptions written. Over the past 2 months, approximately 750 new patients per week have received a prescription for Dupixent from a health care provider.

現在我們來看看最近在美國推出的Dupixent（或稱dupilumab），用於治療中度至重度異位性皮膚炎成年患者。根據我們的合作夥伴賽諾菲公司報告，Dupixent 第二季的全球淨銷售額為 2,900 萬美元。這些銷售額主要反映了美國終端用戶的需求，庫存增加的貢獻微乎其微。我們對該產品上市的進展感到滿意，其處方量也超過了近期在皮膚科領域上市的其他生物製劑。截至上週，已有超過 5000 名醫療保健專業人員開立了 Dupixent 處方，共開出了超過 13,000 張處方。過去兩個月，每週約有 750 名新患者從醫療保健提供者那裡獲得了 Dupixent 的處方。

During the past 2 months, approximately 500 patients per week who are new to the brand have had prescriptions filled. On the market access front, things are progressing well. As we've previously communicated, the 2 largest pharmacy benefits managers, Express Scripts and CVS, provided immediate coverage for launch -- from launch, with utilization management criteria that are consistent with the Dupixent label. We continue to work with payers to try and ensure that all appropriate patients are able to access Dupixent, and expect to have broad market access by the end of the year. Outside of the United States, Dupixent has received a positive CHMP recommendation in July of this year, with a launch expected in Europe later this year.

在過去的兩個月裡，每周大約有 500 名首次使用該品牌的患者獲得了處方。市場進入方面，進展順利。正如我們之前溝通的那樣，兩大藥品福利管理公司 Express Scripts 和 CVS 為該藥物的上市提供了立即保障——從上市之初，其使用管理標準與 Dupixent 的標籤一致。我們將繼續與支付方合作，努力確保所有合適的患者都能獲得 Dupixent，並預計到今年年底將實現廣泛的市場准入。除美國以外，Dupixent 已於今年 7 月獲得 CHMP 的積極推薦，預計將於今年稍後在歐洲上市。

Turning now to Kevzara, or sarilumab, our IL-6 receptor antibody for the treatment of rheumatoid arthritis. Net global sales through the end of the second quarter were $1 million. It is still very early days, given that Kevzara was approved and launched in the United States towards the end of May. The initial feedback from physicians has been positive, and we are working on building market access. We have received EMA approval of Kevzara in the EU, with the launch beginning in August.

現在讓我們來談談 Kevzara，也就是 sarilumab，我們用來治療類風濕性關節炎的 IL-6 受體抗體。截至第二季末，全球淨銷售額為 100 萬美元。鑑於 Kevzara 於 5 月底才獲得美國批准並上市，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。Kevzara 已獲得歐盟 EMA 的批准，將於 8 月開始上市。

Turning now to PRALUENT, or alirocumab. As reported by Sanofi, net sales in the second quarter were $46 million worldwide, with the U.S. accounting for $33 million of the total. While we continue to be disappointed by the uptake of the PCSK9 inhibitor class, we are encouraged by ongoing discussions with payers with respect to improvement in utilization management criteria.

接下來我們來看看 PRALUENT，也就是 alirocumab。根據賽諾菲公司報告，第二季全球淨銷售額為 4,600 萬美元，其中美國市場貢獻了 3,300 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，但我們對與支付方就改進利用管理標準進行的持續討論感到鼓舞。

Earlier this week, CVS announced that it would provide copreferred 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. The potential resolution of our patent dispute with Amgen and anticipated cardiovascular outcomes data for PRALUENT in early 2018 could have an impact on demand.

本週早些時候，CVS 宣布將透過其 CVS Caremark 商業處方集提供 PRALUENT 的共同建議使用權，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。我們與安進公司專利糾紛的潛在解決以及 PRALUENT 在 2018 年初的預期心血管結果數據可能會對需求產生影響。

We remain committed to our efforts to improve PRALUENT access and bring this important product to more patients who can benefit. We're also proceeding with our potential regulatory filings and commercialization planning for Dupixent in asthma and REGN2810, our PD-1 inhibitor, in cutaneous squamous cell carcinoma.

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。我們也正在推進 Dupixent（用於治療氣喘）和 REGN2810（我們的 PD-1 抑制劑，用於治療皮膚鱗狀細胞癌）的潛在監管申報和商業化計劃。

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 second quarter 2017 financial results, driven from the continued strength of our global EYLEA franchise. We are particularly pleased with achieving these results during a period where together with our collaborator, Sanofi, we have launched in the U.S. and are preparing to launch x U.S. 2 significant products, Dupixent and Kevzara.

謝謝你，鮑勃，大家早安。由於全球安樂死產品線的持續強勁表現，再生元公司公佈了2017年第二季強勁的財務業績。我們特別高興的是，在與我們的合作夥伴賽諾菲一起在美國推出並準備在美國推出兩款重要產品 Dupixent 和 Kevzara 的這段時間裡，我們取得了這些成果。

During today's call, I will discuss our financial results and highlight changes to our full year 2017 guidance line items. In the second quarter of 2017, we are in $4.17 per diluted share from non-GAAP net income of $487 million. This represents a year-over-year increase in both non-GAAP diluted EPS and net income of 48%.

在今天的電話會議上，我將討論我們的財務業績，並重點介紹我們對 2017 年全年業績指引項目的變化。2017 年第二季度，我們每股攤薄收益為 4.17 美元，非 GAAP 淨收入為 4.87 億美元。這意味著非GAAP稀釋後每股盈餘和淨收入均較去年同期成長48%。

Regeneron's second quarter 2017 non-GAAP net income excludes noncash share-based compensation expense in the loss on extinguishment of debt, and includes the income tax effect of non-GAAP reconciling items. A full reconciliation of GAAP to non-GAAP earnings is set forth in our earnings release, which can be found on our website. Total revenues in the second quarter of 2017 were $1.47 billion, which represented year-over-year growth of 21% over the second quarter of 2016. Net product sales were $924 million in the second quarter of 2017 compared to $834 million in the second quarter of 2016.

Regeneron 2017 年第二季非 GAAP 淨收入不包括債務清償損失中的非現金股份支付費用，但包括非 GAAP 調整項目的所得稅影響。我們的獲利報告中詳細列出了 GAAP 與非 GAAP 收益的調整情況，您可以在我們的網站上找到該報告。2017 年第二季總營收為 14.7 億美元，比 2016 年第二季年增 21%。2017 年第二季淨產品銷售額為 9.24 億美元，而 2016 年第二季為 8.34 億美元。

EYLEA net product sales in the United States were $919 million in the second quarter of 2017 compared to $831 million in the second quarter of 2016, which represents an increase of 11%. For the 6 months ended June 30, 2017, EYLEA net product sales in the United States were $1.77 billion versus $1.61 billion for the 6 months ended June 30, 2016, an increase of 10%. We are raising our estimated full year 2017 U.S. EYLEA net product sales growth guidance to approximately 10% over 2016.

2017 年第二季度，EYLEA 在美國的淨產品銷售額為 9.19 億美元，而 2016 年第二季為 8.31 億美元，成長了 11%。截至 2017 年 6 月 30 日的 6 個月，EYLEA 在美國的淨產品銷售額為 17.7 億美元，而截至 2016 年 6 月 30 日的 6 個月為 16.1 億美元，成長了 10%。我們將 2017 年全年美國安禮 (EYLEA) 淨產品銷售成長預期上調至比 2016 年成長約 10%。

Similar to the first quarter of 2017, EYLEA experienced another modest decrease in U.S. distributor inventory levels during the second quarter, and remains within our normal 1- to 2-week targeted range. Ex-U. S. EYLEA net product sales, which are recorded by our collaborator, Bayer, were $542 million in the second quarter of 2017, as compared to $486 million in the second quarter of 2016, representing a 12% increase on a reported basis. On an operational or constant-currency basis, sales increased approximately 16%. In the second quarter of 2017, Regeneron recognized $191 million from our share of net profits from EYLEA sales outside the United States. Total Bayer collaboration revenue for the second quarter of 2017 was $210 million.

與 2017 年第一季類似，安怡 (EYLEA) 在第二季美國經銷商的庫存水準再次小幅下降，但仍處於我們正常的 1 至 2 週的目標範圍內。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 年第二季度為 5.42 億美元，而 2016 年第二季度為 4.86 億美元，按報告數據計算增長了 12%。以營運或固定匯率計算，銷售額成長約 16%。2017 年第二季度，Regeneron 從 EYLEA 在美國以外地區的銷售淨利潤中確認了 1.91 億美元。2017 年第二季拜耳合作總營收為 2.1 億美元。

Total Sanofi collaboration revenue was $222 million for the second quarter of 2017. Sanofi collaboration revenue line item primarily consists of reimbursement of Regeneron incurred R&D expenses, reimbursement of Regeneron incurred commercialization-related expenses and our share of profits or losses in connection with the commercialization of antibodies. In the second quarter of 2017, our share of losses in connection with the commercialization of PRALUENT, Dupixent and Kevzara was $122 million. This can be found in Table 4 of our earnings release.

2017 年第二季度，賽諾菲合作總營收為 2.22 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。2017 年第二季度，我們在 PRALUENT、Dupixent 和 Kevzara 的商業化過程中所承擔的損失為 1.22 億美元。這可以在我們發布的收益報告表 4 中找到。

This loss includes our share of increased spending related to the ongoing Dupixent and Kevzara launches in the United States, as well as preparations related to launching Dupixent and Kevzara in other territories. We continue to proactively manage our marketing and selling expenditures in the global commercialization of PRALUENT with our collaborator, Sanofi.

這項損失包括我們在美國持續推出 Dupixent 和 Kevzara 相關的增加支出份額，以及在其他地區推出 Dupixent 和 Kevzara 的準備工作。我們將繼續與合作夥伴賽諾菲積極管理 PRALUENT 全球商業化過程中的行銷和銷售支出。

Netted within these losses were the global sales of PRALUENT, Dupixent and Kevzara, as recorded by our collaborator, Sanofi. For the second quarter of 2017, global net sales were: PRALUENT, $46 million; Dupixent, $29 million; and Kevzara, $1 million. Dupixent net sales in the second quarter largely reflect end-user demand and negligible contribution from inventory build. There were no material Dupixent sales outside the U.S.

在這些損失中，包括了 PRALUENT、Dupixent 和 Kevzara 的全球銷售額，這是我們的合作夥伴賽諾菲的記錄。2017 年第二季全球淨銷售額分別為：PRALUENT 4,600 萬美元；Dupixent 2,900 萬美元；Kevzara 100 萬美元。Dupixent 第二季的淨銷售額主要反映了終端用戶的需求，庫存增加的貢獻微乎其微。Dupixent 在美國以外地區沒有實質的銷售額。

Before I move on from the Sanofi antibody collaboration line, I'd like to inform you that the antibody discovery agreement will be ending in accordance with its terms without any extension on December 31, 2017. The antibody licensing collaboration agreement, the immuno-oncology discovery and development agreement and the immuno-oncology licensing collaboration agreement are not impacted by the expiration of the antibody discovery agreement. The $130 million of 2017 annual funding from Sanofi under the antibody discovery agreement is expected to be fully utilized by the end of the third quarter of 2017. In the second quarter of 2017, other revenue was $114 million versus $23 million as of the second quarter of 2016. This increase was primarily due to the achievement of milestones in connection with our collaboration agreements related to the development of fasinumab, with both Teva and Mitsubishi Tanabe Pharma.

在結束關於賽諾菲抗體合作的發言之前，我想通知各位，抗體發現協議將於 2017 年 12 月 31 日按照協議條款終止，不會延期。抗體發現協議到期不會影響抗體許可合作協議、免疫腫瘤學發現和開發協議以及免疫腫瘤學許可合作協議。根據抗體發現協議，賽諾菲提供的 1.3 億美元 2017 年度資金預計將在 2017 年第三季末全部用完。2017 年第二季其他營收為 1.14 億美元，而 2016 年第二季為 2,300 萬美元。這一成長主要是由於我們在與梯瓦製藥和三菱田邊製藥就法西單抗的開發達成的合作協議中實現了里程碑。

In the second quarter of 2017, we recognized the $25 million substantive milestone from Teva, and the $30 million substantive milestone from Mitsubishi. For further details, you can find the summary of the components of other revenue in the MD&A section of our 10-Q.

2017 年第二季度，我們確認了來自梯瓦製藥的 2,500 萬美元實質里程碑付款，以及來自三菱製藥的 3,000 萬美元實質里程碑付款。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 $440 million for the second quarter of 2017. Our non-GAAP unreimbursed R&D expense, which is calculated as the total non-GAAP R&D, less R&D reimbursements from our collaborators, was $196 million in the second quarter of 2017. Our press release includes all the information that is 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 $925 million to $965 million from our previous guidance of $950 million to $1.025 billion.

接下來談談費用。2017 年第二季非 GAAP 研發費用為 4.4 億美元。2017 年第二季度，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費用）為 1.96 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 9.5 億美元至 10.25 億美元下修並收緊至 9.25 億美元至 9.65 億美元。

Non-GAAP SG&A expense was $262 million for the second quarter of 2017. We are tightening and lowering our full year 2017 guidance of non-GAAP SG&A to $1.12 billion to $1.16 billion from our previous guidance range of $1.14 billion to $1.2 billion.

2017 年第二季非 GAAP 銷售、一般及行政費用為 2.62 億美元。我們將 2017 年全年非 GAAP 銷售、一般及行政費用預期從先前的 11.4 億美元至 12 億美元下調至 11.2 億美元至 11.6 億美元。

Sanofi reimbursement of Regeneron commercialization-related expenses, a line item found within Sanofi collaboration revenue, was $87 million for the second quarter of 2017. We are tightening and lowering our full year 2017 guidance of Sanofi reimbursement of Regeneron commercialization-related expenses, the $370 million to $400 million from our previous guidance range of $385 million to $425 million.

2017 年第二季度，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 8,700 萬美元。我們將收緊並下調賽諾菲對 Regeneron 商業化相關費用的 2017 年全年報銷預期，從之前的 3.85 億美元至 4.25 億美元下調至 3.7 億美元至 4 億美元。

One last operating expense I'd like to review was our cost of collaboration and contract manufacturing. As a reminder, this line item primarily reflects the cost incurred to manufacture commercial supplies for our collaborators. The increase to $61 million for the 3 months ended June 30, 2017 versus $28 million for the 3 months ended June 30, 2016, was primarily driven by higher-than-historical manufacturing losses.

最後我想回顧一下我們的一項營運支出，即合作和合約製造成本。再次提醒，此項主要反映的是我們為合作夥伴生產商業用品所產生的成本。截至 2017 年 6 月 30 日的三個月，虧損額增至 6,100 萬美元，而截至 2016 年 6 月 30 日的三個月，虧損額為 2,800 萬美元，主要原因是製造業虧損高於歷史水準。

Before I conclude my prepared remarks with a review of taxes and our liquidity position, I do want to highlight an out-of-period adjustment to reflect the correction in our accounting for the lease of the Tarrytown, New York facility that was recorded in the second quarter of 2017. The adjustment resulted in the recognition of a $30 million loss on extinguishment of debt related to the March 3, 2017 lease transaction and a corresponding decrease to property plant and equipment. These adjustments consisted entirely of noncash adjustments, and therefore, had no impact on our previously reported amounts in the statement of cash flows. Further details can be found in our most recent 10-Q that was filed earlier this morning. This loss on debt extinguishment has not been included within our non-GAAP results.

在我結束關於稅收和流動性狀況的發言之前，我想重點強調一項期外調整，以反映我們對 2017 年第二季度記錄的紐約州塔里敦設施租賃會計處理的更正。此次調整導致確認了與 2017 年 3 月 3 日租賃交易相關的債務清償損失 3,000 萬美元，並導致固定資產和設備相應減少。這些調整全部屬於非現金調整，因此對我們先前在現金流量表中報告的金額沒有任何影響。更多詳情請參閱我們今天早上早些時候提交的最新 10-Q 表格。這項債務清償損失並未計入我們的非GAAP財務表現。

Turning now to taxes. Our effective tax rate for the second quarter of 2017 was approximately 26%, as compared to approximately 33% for the second 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 27% to 31% from the previous range of 32% to 38%. This updated guidance reflects higher actual and forecasted tax deductions from stock option exercises, given the recent increase in our stock price, as well as lower forecasted losses in foreign jurisdictions.

接下來談談稅務問題。2017 年第二季我們的實際稅率約為 26%，而 2016 年第二季的實際稅率約為 33%。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 32% 至 38% 的區間下調至 27% 至 31% 的區間。鑑於我們股價近期上漲，此次更新後的指導意見反映了股票選擇權行使帶來的實際和預測稅收抵免增加，以及在海外司法管轄區預計損失減少。

As stated on previous calls, there will be volatility in our effective tax rate on a quarter-to-quarter basis since the tax benefits of stock-based compensation is included based on actual exercises in the quarter.

如同先前電話會議所述，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。

From a cash flow and balance sheet perspective, we ended the second quarter of 2017 with cash and marketable securities of $2.3 billion, a level consistent with March 31, 2017. Despite strong quarter 2017 operational results, our cash flow from operations in the second quarter was adversely impacted due to 3 factors: higher inventory levels to support our 2 recent launches, plus more EYLEA inventory to support increased demand; higher Sanofi Bayer and trade account receivable and higher cash tax payments. The tax payments included the final payment related to the Sanofi immuno-oncology collaboration upfront that we received in 2015.

從現金流量和資產負債表的角度來看，截至 2017 年第二季末，我們的現金和有價證券為 23 億美元，與 2017 年 3 月 31 日的水平一致。儘管 2017 年第二季度營運業績強勁，但由於以下三個因素，我們第二季度的經營現金流受到了不利影響：為支持我們最近推出的兩款產品，庫存水平較高；為滿足不斷增長的需求，安樂死庫存增加；賽諾菲、拜耳和貿易應收賬款增加；以及現金稅款支付增加。稅款支付包括我們在 2015 年收到的與賽諾菲免疫腫瘤學合作相關的最終預付款。

Our capital expenditures for the 3 months and 6 months ended June 30, 2017, were $55 million and $105 million, respectively. We are lowering and tightening our full year 2017 capital expenditure guidance to be in the range of $250 million to $285 million from our previously provided range of $300 million to $350 million.

截至 2017 年 6 月 30 日的 3 個月和 6 個月期間，我們的資本支出分別為 5,500 萬美元和 1.05 億美元。我們將 2017 年全年資本支出預期從先前的 3 億美元至 3.5 億美元下修並收緊至 2.5 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. Jason, we'd now like to open the call for Q&A. (Operator Instructions) We will be available in the office after the call for follow-up questions.

謝謝你，鮑伯。傑森，現在我們開始問答環節。（操作員說明）通話結束後，我們將在辦公室為您解答後續問題。

(Operator Instructions) Our first question comes from Ying Huang from Bank of America Merrill Lynch.

（操作員說明）我們的第一個問題來自美國銀行美林證券的黃穎。

I want to ask about EYLEA. It sounds like your competitor, Lucentis, in the U.S. is experiencing actually quarter-over-quarter sequential decline in their sales in 2Q. So I was wondering, what contributed to the strength in EYLEA? And also, what has changed since you've guided single-digit growth in the beginning of the year? And then quickly on Dupixent, any reason why we should see a strong inflection of additional patients add every week instead of just steady in RX every week?

我想諮詢一下關於EYLEA的問題。聽起來你們的競爭對手 Lucentis 在美國的銷售額在第二季確實出現了環比下降。所以我想知道，是什麼因素造就了EYLEA的強大實力？另外，自從年初您帶領公司實現個位數成長以來，發生了哪些變化？那麼，關於Dupixent，有什麼理由讓我們看到每週新增患者數量出現強勁增長，而不是每週處方量保持穩定呢？

Bob, you want to handle the EYLEA question?

鮑勃，你想處理EYLEA的問題嗎？

Yes. EYLEA, as we pointed out earlier, has grown due to a growing of the market, which is partially related to the demographics in the marketplace, and also has grown in terms of market share. We believe some of that growth in market share is related to the positive data we've seen with EYLEA in diabetic macular edema. And in terms of a decline in Lucentis, there's multiple factors that could contribute to it, including any discounting they're doing, which relates to growth to net differences. With regards to Dupixent, we have payers coming onboard on a regular basis. As I said, we expect market access, broad market access, by the end of the year. Patient claims are still making their way through the pipeline in many cases, so we do expect more prescriptions being dispensed. And we continue to educate on disease awareness to let patients who've been disenfranchised from the system get back into their physicians and benefit from the product.

是的。正如我們之前指出的，安怡的成長是由於市場的成長，這部分與市場人口結構有關，同時安怡的市佔率也有所成長。我們認為市場佔有率的部分成長與我們在 EYLEA 治療糖尿病性黃斑水腫方面看到的正面數據有關。至於 Lucentis 的下跌，可能有多種因素導致，包括他們進行的任何折價，這與成長和淨差額有關。關於Dupixent，我們有穩定的支付方加入。正如我所說，我們預計到今年年底將獲得市場准入，廣泛的市場准入。在許多情況下，患者的理賠申請仍在處理中，因此我們預計會有更多處方藥物被配發。我們持續進行疾病意識教育，讓那些被醫療體系排斥的患者能夠重新獲得醫生的診治，並從產品中受益。

It's Len. Let me just amplify a little bit on the Dupixent question there. Remember, the first question that we all were interested in, would there be a bolus? Would there be a large number of patients who would get a prescription very soon at the launch and then the number of the prescriptions written go down dramatically?. We did not see that. We've seen a very steady number of prescriptions written. As we indicated somewhere over the last couple of months, it's been very steady on a weekly basis. The way that number could -- so we're very pleased that there's no bolus. Obviously, this is what the system, if you will, can turn out right now. How could that grow? We can see in -- I'm just talking about on the written prescription side, not the fill side, that, that could grow, obviously, if we see an increase in the number of prescribers, which takes time, but we're starting to see that. Or whether or not the prescribers start to write prescriptions for patients who are not just their most severe patients. We're seeing, from what we can tell in here, that as you would expect with the launch of a new class of drug, that patients who have been prescribed the drug typically are the most severe of the patients. So that -- those are ways that the number could go up. But first stop in this was to make sure there wasn't just a bolus, and it was all going down, which we can now say, at least, over the first period of this launch, that's not the case.

是倫。關於Dupixent的問題，我再補充一點。還記得我們大家最關心的第一個問題嗎？那就是是否會注射高劑量胰島素？是否會在產品上市初期有大量患者很快獲得處方，然後處方數量急劇下降？我們沒有看到這一點。我們看到處方開立數量一直非常穩定。正如我們在過去幾個月中多次提到的，每週的波動都非常穩定。這個數字可能會是這樣——所以我們很高興不需要追加劑量。顯然，這就是目前這個系統（如果可以這麼稱呼的話）所能產生的結果。它怎麼可能發展壯大？我們可以看到——我指的是處方開立方面，而不是實際配藥方面——顯然，如果我們看到開處方的醫生數量增加，處方開具方面可能會增長，這需要時間，但我們已經開始看到這種情況了。或者，開處方的醫生是否會開始給病情不只是最嚴重的病人開處方。從我們這裡觀察到的情況來看，正如你所預料的那樣，在新藥上市後，服用這種藥物的患者通常是病情最嚴重的患者。所以，這些都是導致數字上升的途徑。但首先要確保不只是注射了一劑，而是全部都輸了下去，我們現在可以說，至少在這次上市的最初階段，情況並非如此。

On that Len, I think it's important to mention that now as these patients are coming back to their physician, we're hearing many of these patients are having very, very positive results in terms of reduced lesions and improved itch, and that is really contributing to patient satisfaction.

關於這一點，Len，我認為有必要提一下，現在這些患者正在返回他們的醫生那裡，我們聽說很多患者在皮損減少和瘙癢改善方面都取得了非常非常積極的效果，這確實有助於提高患者的滿意度。

Yes. I just wanted to -- this is George, I wanted to point out a couple of things. Despite the mechanics of the health care system and reimbursement and rebates and all this, I'd like to think that physicians and patients are still driven quite a bit by how the drugs are actually performing and making a difference in their lives. So I'd like to think that one of the reasons that EYLEA is growing in market share is because of the recognition by physicians and patients of what a difference it's making in their experiences. And I think, as Bob points out, we hope to see that the same will continue to be true as we're seeing from the early reports on Dupixent, and I think another very important thing to realize about Dupixent is also the long view. As I noted in my remarks. We are developing this for a very large number of allergic indications. The data right now, the early data and including pivotal study data is all very promising. So long-term growth in dupilumab is going to be by the recognition that it may be an important drug for many different allergic conditions, starting with asthma and going onward. And moreover that in a single patient, hopefully, we'll be able to show in convincing ways, in a single patient, it will be able to simultaneously benefit multiple of their allergic conditions. And so we think that if the medicine is doing and bringing the sort of benefit that we think it's doing to that patients that, that recognition will drive, of course, use because of the benefit it provides.

是的。我只是想——我是喬治，我想指出幾件事。儘管醫療保健系統有其運作機制、報銷和回扣等等，但我仍然認為，醫生和患者在很大程度上還是受藥物的實際療效以及藥物對他們生活的影響所驅動的。所以我認為，EYLEA市場份額不斷增長的原因之一是醫生和患者認識到它為他們的體驗帶來了多大的改變。正如鮑勃指出的那樣，我們希望看到這種情況繼續下去，就像我們從 Dupixent 的早期報告中看到的那樣。我認為關於 Dupixent 需要認識到的另一個非常重要的事情是長遠考慮。正如我在發言中提到的那樣。我們正在開發這種藥物，以用於治療多種過敏性疾病。目前的數據，包括早期數據和關鍵研究數據在內，都非常令人鼓舞。因此，dupilumab 的長期成長將來自於人們認識到它可能是治療多種不同過敏性疾病的重要藥物，從氣喘開始，並逐步擴展到其他疾病。而且，我們希望能夠以令人信服的方式證明，對於單一患者而言，它能夠同時改善其多種過敏症狀。因此我們認為，如果這種藥物確實能為患者帶來我們認為它正在帶來的益處，那麼這種認可當然會促進其使用，因為它能帶來益處。

We have Chris Raymond from Raymond James.

我們邀請了來自Raymond James的Chris Raymond。

I got a question on the pipeline. So, Len, I heard you say in the recent meeting, I heard you highlight Regeneron 2810, your PD-1. When you are asked to talk about which pipeline program excites you the most. So I think we know the clinical plan that you guys have outlined is unique. You guys have seen now what looks like a pretty novel and quick path to market, but maybe you can talk about the biology of the molecule that makes you think that sort of head to head, this should be better maybe than other more advanced PD-1s. Just maybe talk about what drives you to highlight that molecule as the most exciting pipeline drug.

我收到一個關於輸油管的問題。所以，Len，我聽你在最近的會議上說過，我聽你重點介紹了 Regeneron 2810，你的 PD-1。當被問到你最感興趣的人才培育計畫是什麼。所以我認為我們知道你們所製定的臨床方案是獨一無二的。你們現在看到的似乎是一種相當新穎且快速的上市途徑，但也許你們可以談談這種分子的生物學特性，正是這種特性讓你們認為，在直接比較中，它應該比其他更先進的PD-1藥物更好。或許可以談談是什麼促使您將該分子列為最令人興奮的在研藥物。

Yes. I'm going to let George deal with that question. But before I turn it over to him, I just wanted to point out that this is tough business. And if you look at each of our programs and what's been going on around us, it's been quite remarkable. If you just think about it, in the PD-1 space, which George will get into in a bit more, we've seen failures of PD-L1 to deliver survival benefits where PD-1 agents had. We've seen a failure of a PD-1 agent where another PD-1 agent was successful. In the PCSK9 space, we've seen the failure of one agent to get to market because of issues in, from what I understand, immunogenicity. In the IL-4/13 space, we've seen people historically have failed with even going after the right target and people having failed by going after the wrong target, such as going after IL-13, and maybe people not getting even optimum results going after IL-5. If you think about EYLEA, we've seen a lot of explanations about why people shouldn't be able to get long-term benefit in it. The savior for this was going to be PDGF and anti-VEGF therapy was bad. And you've heard George, I think, put out a very convincing case that that's just not the case, and that PDGF has fallen by the wayside. Just yesterday, in the IL-6 space, you've seen a group of people who chose IL-6 ligand instead of the IL-6 receptor, and that didn't seem to go so well, at least based on the vote of the advisory panel. So I just want to say that there's a lot that goes on, and maybe the guy who makes all these choices for us, and it seems to have gotten -- done pretty good in the batting average can comment on the PD-1 space. George?

是的。這個問題就交給喬治來處理吧。但在我把麥克風交給他之前，我想指出，這可不是件容易的事。如果你看看我們的每個項目以及我們周圍發生的事情，你會發現這非常了不起。仔細想想，在 PD-1 領域（喬治稍後會更詳細地談到這一點），我們已經看到 PD-L1 未能帶來 PD-1 藥物所帶來的生存益處。我們看到一種 PD-1 藥物失敗了，而另一種 PD-1 藥物卻成功了。在 PCSK9 領域，我們已經看到一種藥物因免疫原性問題而未能上市，據我了解，這是因為免疫原性問題。在 IL-4/13 領域，我們看到歷史上有些人即使瞄準了正確的目標也失敗了，有些人因為瞄準了錯誤的目標（例如 IL-13）而失敗，甚至有些人即使瞄準了 IL-5 也沒有獲得最佳結果。以愛樂製藥為例，我們已經看到了很多關於為什麼人們不應該從中獲得長期利益的解釋。PDGF原本有望成為此病的救星，而抗VEGF療法則效果不佳。我想你已經聽喬治提出了一個非常有說服力的論點，證明事實並非如此，PDGF 已經被淘汰了。就在昨天，在 IL-6 領域，我們看到一群人選擇了 IL-6 配體而不是 IL-6 受體，但結果似乎不太理想，至少根據顧問小組的投票來看是如此。所以我想說的是，有很多事情正在發生，也許為我們做出所有這些選擇的人，而且似乎在打擊率方面做得相當不錯，可以對 PD-1 領域發表評論。喬治？

Yes. I was going to actually bring up a lot of the same examples, as Len just did, in terms of pointing out how really difficult this business is, how it really is so challenging. It's really such a industry of failure because the bar is rightfully set so high. I mean, we want to be bringing forward important, effective and safe medicines to patients, and that, frankly, is probably the single hardest thing that we as a society actually do in terms of discovering and developing products. And while I was reading my comments, I have to say I was shocked and stunned at how productive our people have been over so many years to produce so many product candidates, and as Len said, I'm a big track-record guy. Over and over again, we've made the right decisions about which targets about picking and selecting the right -- out of many candidates, the right candidates to bring forward, and over and over again, we more likely than not have been proven right. And I think that this is something that is incredibly vastly underappreciated in this industry, how much of a role institutional knowledge plays in having a senior experienced leadership team that has the capability to over and over again make these decisions and prolong their collective memories to help make these sort of decisions. And if you go anywhere else, and you look how long the people who are making these decisions have been around at that particular place, and it's just a couple of years. Here our senior management team at all levels, and I'm not just talking about me and Len and then the other most senior people, but we have, in general, people, 15, 20 years who have been leading various efforts, and we have enormous collective memory and institutional memory here. And it's only with that, that you could have that sort of track record that can lead to the discovery of dozens and dozens of product candidates and be moving them forward, and in more cases than not, be making the right decisions and making your bets. And whether it's picking PD-1 as opposed to PD-L1 and picking the right PD-1 antibody or picking IL-6 receptor versus IL-6 and picking the right IL-6 receptor antibody or picking the right antibody for PCSK9 and picking the right target in the field of allergy, which nobody else happened to have picked in the entire world, this all comes from incredible internal genius and institutional memory that is very rare, and as I said, represents one of the hardest things we do as a society. The track record in the rest of the world is overwhelmingly one of failure and no, not everything we do will work. Not everything we do will succeed. We have an amazing track record because of this institutional memory and the genius that we have here.

是的。我本來也想舉出很多和 Len 剛才一樣的例子，來說明這個產業有多艱難，多麼具有挑戰性。這個行業失敗率真的很高，因為門檻確實設得很高。我的意思是，我們希望為患者帶來重要、有效且安全的藥物，坦白說，這可能是我們作為一個社會在發現和開發產品方面所做最困難的事情。在閱讀我的評論時，我不得不說，我感到震驚和難以置信，我們的員工多年來如此高效地開發出了這麼多產品候選產品，正如 Len 所說，我非常重視業績記錄。我們一次又一次地做出了正確的決定，從眾多候選人中挑選出合適的候選人，推舉出最合適的候選人，而且一次又一次地，事實證明我們的決定是正確的。我認為，在這個行業中，這一點被嚴重低估了，那就是機構知識在擁有一支經驗豐富的高級領導團隊方面發揮著多麼重要的作用，這支團隊有能力一次又一次地做出這些決定，並延長他們的集體記憶來幫助做出這類決定。如果你去其他地方，看看那些做出這些決定的人在那個地方待了多久，你會發現也就幾年而已。我們各個層級的高階管理團隊，我指的不僅是我和 Len 以及其他最高層級的人員，而是我們一般都有從業 15 到 20 年、領導過各種工作的人員，我們這裡擁有巨大的集體記憶和機構記憶。只有這樣，你才能擁有那種能夠發現數十個候選產品並推動它們向前發展的業績記錄，而且在大多數情況下，你還能做出正確的決定並進行正確的投資。無論是選擇 PD-1 而不是 PD-L1 並選擇正確的 PD-1 抗體，還是選擇 IL-6 受體而不是 IL-6 並選擇正確的 IL-6 受體抗體，又或是選擇正確的 PCSK9 抗體並在過敏領域選擇正確的靶點（而我所說的全世界這個受體抗體，又或是選擇正確的 PCSK9 抗體並在過敏領域選擇正確的靶點（而我所說的世界其他人恰好是極其重要的社會之一，這一切都源於我們難以置信的內部和罕見的事情。世界其他地方的記錄絕大多數都是失敗的，而且，不，我們所做的每一件事都不會成功。我們做的並非每件事都會成功。我們之所以能有如此輝煌的成就，是因為這裡有豐富的機構經驗和傑出的人才。

We have Geoffrey Porges off Leerink Partners.

我們有來自 Leerink Partners 的 Geoffrey Porges。

I just wanted to follow up on the questions about Dupixent, particularly the launch. You've mentioned that 13,000 patients have been prescribed Dupixent, but could you tell us how many of those have converted to fill prescriptions? And then secondly, Bob, could you give us a sense of what -- of the patients that have had one filled prescription, what proportion of them are filling a second, and ideally, a third prescription, i.e., what's the treatment persistence after patients have started on Dupixent? Just wanted to clarify how this is going.

我只是想就 Dupixent 的相關問題，特別是上市事宜，進行一些後續的討論。您提到有 13,000 名患者被開了 Dupixent 處方，但您能告訴我們其中有多少人最終完成了處方配藥嗎？其次，鮑勃，你能否告訴我們，在已經完成一次處方配藥的患者中，有多少比例的人會完成第二次處方配藥，理想情況下，還會完成第三次處方配藥？也就是說，患者開始使用 Dupixent 後，治療的持續性如何？我只是想確認一下事情進展如何。

Well, Jeff, it's Len. I mean, I think Bob that can comment if he has the number of how many patients we think have actually converted. There's obviously a lag. I think the interesting metric for us is that the number of new prescriptions written over the last several months, each week has been in the study range of around 750 new patients per week, and there's been a steady new patients to the brand, as judged by IMS-type data of over 500. So that gives you a little bit of an idea. That's obviously not the same -- it's not the 750 that got the prescription this week are the ones that are getting the prescription filled. But that gives you an idea of where the launch is sort of -- how it's, at least, behaving on a weekly basis for the last several months. Bob, do we have an idea of how many patients are actually on product at this time?

傑夫，我是倫。我的意思是，我認為鮑伯可以評論一下，他是否掌握了我們認為實際轉化了多少患者的數據。顯然存在延遲。我認為對我們來說，有趣的指標是，在過去的幾個月裡，每週開出的新處方數量都在研究範圍內，每周大約有 750 名新患者，而且根據 IMS 類型的數據判斷，該品牌的新患者數量一直穩定在 500 人以上。這樣你就能大概了解狀況了。這顯然不一樣──這週拿到處方的750人並不是最終拿到處方的人。但這可以讓你大致了解這次發布的情況——至少在過去幾個月裡，它每週的表現如何。鮑勃，我們是否知道目前有多少患者正在使用該產品？

I think it's fair to say that most patients have received 1 or 2 prescriptions based upon the timing of the launch. So to talk about it here -- and it's too early to get into the specifics of that.

我認為可以公平地說，根據產品上市的時間，大多數患者都收到了 1 到 2 張處方。所以，在這裡談論這件事——現在深入探討細節還為時過早。

We have Alethia Young from Crédit Suisse.

我們邀請到了來自瑞士信貸的阿萊西亞·楊。

I guess just one on the Complement program. When might we be in the position to get some of the early data and how are you kind of thinking about dosing in that program? Or maybe is that something you're going to find out in the Phase I?

我猜只有一位參加補錄節目。我們什麼時候才能獲得一些早期數據？你們是如何考慮該項目的劑量方案的？或許這是你將在第一階段找到答案的問題？

Yes. It's a little bit early to tell you much about that, but we'll -- we, of course, are trying to get all the information we can out of that Phase I program. When we have it, we'll make it available. Next question?

是的。現在透露太多資訊還為時過早，但是我們當然會盡力從第一階段專案中獲取所有資訊。有了之後，我們會立即提供。下一個問題？

We have Robyn Karnauskas from Citigroup.

我們邀請了花旗集團的 Robyn Karnauskas。

So just a question on the asthma study. So I know you mentioned that patient populations are different, but are there -- similar, but are there any differences between the 2b and the 3 that you think are notable? And I know -- I think you're stratifying patients by ease of eosinophil counts. What happens if you are only successful in high eosinophils, but not among the low eosinophil counts?

關於氣喘研究，我有個問題。我知道您提到患者群體有所不同，但是 2b 和 3 之間是否存在相似之處，或者您認為存在哪些值得注意的差異？我知道——我認為你們是根據嗜酸性粒細胞計數的難易程度對患者進行分層。如果你只在高嗜酸性粒細胞計數患者中成功，而在低嗜酸性粒細胞計數患者中失敗，會發生什麼情況？

Yes. I think that as I described in my comments, the populations are actually very similar. Obviously, when you have such a successful study, you do your best to reproduce it with the least number of modifications and changes. I mean, our first study was rather standard. It wasn't that we did anything so special. Other than that, we studied both the all-comer population and then we looked in both the high- and the low-yield subset. We designed our study to look in the all-comer population, but we also designed it to look in the high-yield population. If our data is limited to the high yields, it would be a little less differentiating perhaps than we think it might be compared to the other agents that are out there in development right now. But as you know, the real excitement is if it's positive in the all-comer population, nobody else has data that shows that a biologic can really affect the all-comer population.

是的。我認為正如我在評論中所描述的那樣，這些人群實際上非常相似。顯然，當一項研究取得如此成功時，你會盡最大努力以最少的修改和變化來重現它。我的意思是，我們的第一個研究相當常規。並不是說我們做了什麼特別的事。除此之外，我們也研究了所有參與者，然後研究了高產量和低產子群體。我們的研究設計旨在考察所有人群，但我們也設計了針對高產量人群的研究。如果我們的數據僅限於高收益產品，那麼與目前正在研發的其他產品相比，其差異性可能不如我們想像的那麼大。但正如你所知，真正令人興奮的是，如果它對所有人群都有效，那麼其他任何生物製劑都沒有數據表明它能夠真正影響所有人群。

We have Carter Gould from UBS.

我們請到了瑞銀集團的卡特古爾德。

For Bob, I guess, thanks for all the color. I recognize it's early in the launch, but generally speaking, for those plants that have opened up access, how satisfied are you with the step out of prior authorization criteria in place? And for those that have yet to open up access, can you characterize how those conversations are going? Is it really just sort of inertia from the plants' focus on rebates or step edits versus them sort of just taking a dug-in stance?

我想，應該感謝鮑伯帶來的所有美好。我知道現在還處於啟動初期，但總的來說，對於那些已經開放准入的工廠而言，您對取消事先授權標準的這一舉措有多滿意？對於那些尚未開放存取權限的國家，您能否描述一下這些對話的進展？難道只是因為工廠專注於退款或逐步修改而產生的慣性，而不是採取強硬立場嗎？

So just very quickly, in the interest of time, we can say about a 1/3 of the places, where decisions have been made, have been made according to the label and we're very pleased. About another 1/3, just roughly speaking, have made decisions, which is slightly more restrictive. They might have -- require a topical calcineurin inhibitor as opposed to just a topical corticosteroid. A few of those have required systemic steroids, and there's still another 35-or-so percent that we're working on, which some of them have automatic blocks and some of it just takes time. But we hope to, as we said, get broad access towards the -- by the end of the year. Sanofi and Regeneron are working very hard at this, and I think I would have to characterize this based on other metrics. We've looked at other launches, and it's going very well in this modern era.

為了節省時間，我們簡單說一下，大約有三分之一的地方已經做出了決定，這些決定都符合標籤所示，我們對此非常滿意。粗略估計，還有大約三分之一的人做出了決定，這個決定稍微嚴格一些。他們可能需要使用局部鈣調神經磷酸酶抑制劑，而不是只使用局部皮質類固醇。其中一些病例需要使用全身性類固醇，還有大約 35% 的病例我們正在治療，其中一些病例有自動阻斷機制，而另一些病例則需要時間。但正如我們所說，我們希望到今年年底能夠獲得廣泛的訪問權限。賽諾菲和再生元在這方面非常努力，我認為我需要根據其他指標來描述這種情況。我們考察過其他一些產品發布，在當今時代，它們的表現都非常出色。

All right. I know many of you were in queue and didn't get a chance to ask your questions. Just send us an email, and we'll make sure to follow up with you. Jason?

好的。我知道你們很多人都在排隊，沒有機會提問。只需給我們發一封電子郵件，我們一定會盡快與您聯繫。傑森？

All right, operator. Thank you.

好的，接線生。謝謝。

Thank you. Ladies and gentlemen, this concludes today's conference. Thank you for participating, and you may now disconnect.

謝謝。女士們、先生們，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。