雷傑納榮製藥 (REGN) 2016 Q2 法說會逐字稿

Welcome to the Regeneron Pharmaceuticals second-quarter 2016 earnings conference call. My name is Sylvia and I will be your operator for today's call.

歡迎參加 Regeneron Pharmaceuticals 2016 年第二季財報電話會議。我叫西爾維婭，今天將由我來為您接聽電話。

(Operator Instructions)

（操作說明）

I will now turn the call over to Dr. Michael Aberman. Dr. Aberman, you may begin.

現在我將把電話交給邁克爾·阿伯曼博士。阿伯曼博士，你可以開始了。

Thank you, and good morning and welcome to Regeneron Pharmaceutical's second-quarter 2016 conference call. An archive of this webcast will be available on our website under Events and presentations for 30 days. Joining me on the call today are Dr. Leonard Schleifer, Founder, President and Chief Executive Officer; George Yancopoulos, Founding Scientist, President of Regeneron Laboratories, and Chief Scientific Officer; Bob Terifay, Executive Vice President, Commercial; and Bob Landry, Chief Financial Officer. After our prepared remarks, we will open the call for Q&A.

謝謝，早安，歡迎參加 Regeneron Pharmaceutical 2016 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。今天與我一起參加電話會議的有：創辦人、總裁兼執行長 Leonard Schleifer 博士；Regeneron Laboratories 的創始科學家、總裁兼首席科學官 George Yancopoulos；商業執行副總裁 Bob Terifay；以及財務長 Bob Landry。在我們發言完畢後，我們將開放問答環節。

I would also like to remind you that remarks made on this call include forward-looking statements about Regeneron. Such statements may include, but are not limited to, those related to Regeneron and its products and businesses, sales and expense forecasts, financial forecasts, development programs, collaborations, finances, regulatory matters, coverage and reimbursement matters, intellectual property, litigation matters and competition. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in such statements.

我還要提醒各位，本次電話會議中發表的言論包含 Regeneron 的前瞻性陳述。此類聲明可能包括但不限於與 Regeneron 及其產品和業務、銷售和支出預測、財務預測、開發計劃、合作、財務、監管事項、承保和報銷事項、智慧財產權、訴訟事項和競爭相關的聲明。每項前瞻性聲明都存在風險和不確定性，可能導致實際結果和事件與此類聲明中預測的結果和事件有重大差異。

A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, or SEC, including its Form 10-Q for the quarter ended June 30, 2016, which was filed with the SEC this morning. Regeneron does not undertake any obligation to update publicly any forward-looking statement, whether as a result of new information, future events or otherwise.

有關這些及其他重大風險的更完整描述，請參閱 Regeneron 向美國證券交易委員會 (SEC) 提交的文件，包括其截至 2016 年 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公司不承擔任何公開更新任何前瞻性聲明的義務，無論是由於新資訊、未來事件或其他原因。

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

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

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

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

Thank you, Michael. And a very good morning to everyone who has joined us on the call and webcast today. Before I turn the call over to my colleagues, who will discuss our scientific, commercial and financial performance, I'd like to take a few minutes to give you some broader perspective on Regeneron and our business.

謝謝你，麥可。各位早安，感謝今天參加電話會議和網路直播的朋友們。在我將電話轉交給我的同事們，他們將討論我們的科學、商業和財務業績之前，我想花幾分鐘時間，向大家更全面地介紹一下 Regeneron 和我們的業務。

Regeneron continues to advance its mission to bring important new medicines to patients in need. EYLEA is our drug used to treat a number of potentially blinding diseases; and with millions of injections administered each year, it is one of our most important approved products and continues to grow well globally. EYLEA is now at an annual global net sales run rate that exceeds $5 billion. This has been driven both by the approval of EYLEA in new indications, as well as new data that have further increased the confidence of physicians in this product.

再生元公司將繼續推動其使命，為有需要的患者帶來重要的創新藥物。EYLEA 是我們用於治療多種可能導致失明的疾病的藥物；每年註射量達數百萬次，是我們最重要的核准產品之一，並且在全球範圍內持續增長。安樂目前全球年淨銷售額已超過 50 億美元。這既得益於EYLEA獲準用於新的適應症，也得益於新的數據進一步增強了醫師對該產品信心。

Thanks to our long-standing belief and investment in science and technology, we are now in the midst of a new product cycle, which has the potential to impact multiple disease settings. This investment in science has resulted in Praluent, our PCSK9 antibody for lowering LDL cholesterol, and additional potential near-term approvals that could address rheumatoid arthritis and atopic dermatitis. Our late stage pipeline also includes programs in asthma, pain, respiratory syncytial virus, and the immunotherapy of cancer.

由於我們長期以來對科學技術的信念和投入，我們現在正處於一個新的產品週期之中，這有可能對多種疾病領域產生影響。這項對科學的投資催生了 Praluent，這是一種用於降低 LDL 膽固醇的 PCSK9 抗體，並且預計在近期獲得其他藥物的批准，用於治療類風濕性關節炎和異位性皮膚炎。我們的後期研發管線還包括氣喘、疼痛、呼吸道合胞病毒和癌症免疫療法等領域的項目。

Our earlier pipeline opportunities continue to grow, with a total of 15 product candidates currently in clinical development, including 7 that we are developing independently, with several more expected to enter the clinic in the near term, making for a pipeline that can address potential opportunities ranging from rare orphan diseases, such as Fibrodysplasia ossificans progressiva, or FOP, to emerging infectious diseases, epidemics such as Zika. George will provide specific details on some of these programs later in this call.

我們早期的研發管線機會持續成長，目前共有 15 個候選產品處於臨床開發階段，其中 7 個是我們獨立開發的，預計近期還將有更多產品進入臨床階段，這使得我們的研發管線能夠應對從罕見孤兒病（如進行性骨化性纖維發育不良症，簡稱 FOP）到新興有機傳染病（如寨卡病毒）等各種潛在機卡病毒。喬治稍後將在本次通話中詳細介紹其中一些項目。

All of these opportunities are the results of investments we made in science and technology over the last 20 years, yielding a pipeline that is entirely home-grown. Our commitment to the long term is unwavering, as we invest in the next generation of technologies to support our future pipeline, for example, our Regeneron Genetics Center and our investment in technologies with companies in the areas of gene editing and cell therapy, such as Intellia and Adicet, which are synergistic with our existing capabilities.

所有這些機會都是我們過去 20 年在科學技術領域投資的成果，從而形成了一條完全自主研發的人才儲備庫。我們對長期發展的承諾堅定不移，我們投資於下一代技術以支持我們未來的產品線，例如我們的 Regeneron 遺傳學中心，以及我們對基因編輯和細胞治療領域公司（如 Intellia 和 Adicet）的技術投資，這些技術與我們現有的能力具有協同效應。

I should also mention that we recognize that we operate in a rapidly changing environment that poses new challenges to the commercialization of our products, and we continue to try and develop innovative solutions to address these issues.

我還應該提到，我們認識到我們所處的環境瞬息萬變，這為我們的產品商業化帶來了新的挑戰，我們將繼續努力開發創新解決方案來解決這些問題。

Lastly, we believe it's absolutely essential to attract the best and brightest minds to scientific careers and to elevate the place of science in our society. Therefore, we were thrilled to announce in May that Regeneron was selected as the new sponsor of the Science Talent Search.

最後，我們認為吸引最優秀、最聰明的人才從事科學事業，提昇科學在社會中的地位，是絕對必要的。因此，我們非常高興地在五月宣布，Regeneron 被選為科學人才選拔賽的新贊助商。

Regeneron is only the third sponsor in this renowned 75-year history of this high school science talent competition, which was previously sponsored by Intel and before that by Westinghouse. George and I are both alumni of the Science Talent Search and we believe the program plays a vital role in encouraging talented young people to pursue a path in science and engineering.

Regeneron 是這項擁有 75 年歷史的著名高中科學才能競賽的第三位贊助商，此前該競賽曾由 Intel 贊​​助，再之前由 Westinghouse 贊助。喬治和我都是科學人才選拔計劃的校友，我們相信該計劃在鼓勵有才華的年輕人追求科學和工程領域方面發揮著至關重要的作用。

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

介紹完畢，現在讓我把電話交給喬治。

Thank you, Len, and a very good morning to everyone who has joined us today. I'd like to begin with progress in our late stage pipeline.

謝謝Len，也祝今天到場的各位早安。我想先談談我們後期研發管線的進展。

In the second quarter, we reported positive data from three Phase 3 studies of dupilumab, our interleukin 4 and 13 blocker in patients with uncontrolled moderate to severe atopic dermatitis, which is a chronic inflammatory skin disease. Dupilumab is the first systemic therapy to show positive Phase 3 results in this indication.

第二季度，我們公佈了三項針對難治性中度至重度異位性皮膚炎（一種慢性發炎性皮膚病）患者的3期臨床試驗的積極數據，這些試驗使用了我們的白細胞介素4和13阻斷劑dupilumab。Dupilumab 是第一個在該適應症中顯示出積極的 3 期臨床試驗結果的全身性療法。

On our last earnings call, we talked about the positive data from the first two Phase 3 studies, SOLO 1 and SOLO 2, which studied dupilumab as a monotherapy. In June, we just recently reported the results from the third study, LIBERTY AD CHRONOS, which was a long-term study that investigated dupilumab in combination with topical corticosteroids, which are currently the standard of care in the United States for the treatment of this difficult disease. Overall, the efficacy observed in the CHRONOS study was very consistent with the previously reported positive Phase 3 SOLO 1 and SOLO 2 studies of dupilumab in the monotherapy setting.

在上次財報電話會議上，我們討論了前兩項 3 期研究 SOLO 1 和 SOLO 2 的正面數據，這兩項研究分別以度普利尤單抗作為單藥療法。今年 6 月，我們剛剛公佈了第三項研究 LIBERTY AD CHRONOS 的結果，這是一項長期研究，旨在調查度普利尤單抗與局部皮質類固醇聯合用藥的療效，而局部皮質類固醇目前是美國治療這種疑難雜症的標準療法。總體而言，CHRONOS 研究中觀察到的療效與先前報告的 dupilumab 單藥治療的 3 期 SOLO 1 和 SOLO 2 研究的正面結果非常一致。

While the primary end point of the CHRONOS study was assessed at 16 weeks, the study continued until 52 weeks, and efficacy was sustained in both the dupilumab 300-milligram weekly, as well as the 300-milligram every other week dose groups through this one-year mark. At 16 weeks, about 40% of the patients in both dupilumab dose groups achieved clear or almost clear skin status as measured by the Investigator Global Assessment score, compared to about 12% of the patients in the topical steroid-only arm. Nearly two-thirds of the patients receiving dupilumab achieved a 75% improvement in the average improvement in the overall skin score as assessed by the Eczema Area and Severity Index, or the EZ score, compared to about 23% of patients in the topical steroid-only arm.

雖然 CHRONOS 研究的主要終點是在 16 週時進行評估的，但該研究持續到 52 週，並且在 dupilumab 300 毫克每週劑量組和 300 毫克每兩週劑量組中，療效均持續到這一年。16 週時，根據研究者總體評估評分，兩個 dupilumab 劑量組中約 40% 的患者達到了皮膚完全清除或幾乎完全清除的狀態，而僅使用局部類固醇的患者中只有約 12% 達到了這一狀態。在接受度普利尤單抗治療的患者中，近三分之二的患者在濕疹面積和嚴重程度指數（EZ 評分）評估的整體皮膚評分平均改善率方面取得了 75% 的改善，而僅接受局部類固醇治療的患者中，這一比例約為 23%。

This was the first long-term Phase 3 study to show that dupilumab in combination with topical steroids was superior to topical steroids alone and provided sustained efficacy and significantly improved measures of overall disease severity, skin clearing, itching, and quality of life through one year of treatment.

這是第一個長期 3 期研究，結果表明 dupilumab 與局部類固醇聯合使用優於單獨使用局部類固醇，並且在一年的治療過程中，能夠持續有效並顯著改善疾病總體嚴重程度、皮膚清除、瘙癢和生活質量等指標。

The overall rate of adverse events and serious adverse events was comparable between the groups treated with dupilumab in combination with topical steroid and the topical steroids alone. Serious and/or severe (Audio Difficulties) numerically higher in the topical steroid-alone group.

接受度普利尤單抗合併局部類固醇治療的組別與僅接受局部類固醇治療的組別相比，不良事件和嚴重不良事件的總體發生率相當。局部類固醇單獨使用組的嚴重和/或重度（聽力困難）發生率較高。

Adverse events that were noted to have a higher rate with dupilumab treatment included injection site reactions, which were seen in 20% of the patients on the dupilumab weekly arm, 16% of the patients in the dupilumab every two-week arm, and 9% of the patients in the placebo plus topical steroid-alone arm; and conjunctivitis, which was observed in 19% of patients in the dupilumab weekly arm, 13% of patients in the dupilumab every other week arm, and 8% of patients in the topical steroid-alone arm. About 22% of the patients in the placebo group, 23% of the patients in the dupilumab weekly group, and 28% of the patients in the dupilumab every other weekly group had a reported history of allergic conjunctivitis coming into the study.

接受度普利尤單抗治療的患者中，注射部位反應的發生率較高，其中每週一次度普利尤單抗治療組的患者中有 20% 出現注射部位反應，每兩週一次度普利尤單抗治療組的患者中有 16% 出現注射部位反應，而安慰劑加氏類固醇較高單藥治療組的患者中有 9% 治療組中有 9% 的出現結膜炎，每兩週一次度普利尤單抗治療組的患者中有 13% 出現結膜炎，而局部類固醇單藥治療組的患者中有 8% 出現結膜炎。安慰劑組中約 22% 的患者、每週接受度普利尤單抗治療組中約 23% 的患者、每隔一週接受度普利尤單抗治療組中約 28% 的患者在進入研究時有過敏性結膜炎病史。

These one-year results from the CHRONOS study further suggest that dupilumab impacts the aberrant activation of the interleukin 4-13 pathway and results in significant efficacy, without the side effects associated with immune suppressing therapies. In this regard, and very importantly, we have not observed an increase in overall infections or serious infections in our atopic dermatitis program to date. The US BLA submission has been completed, and we look forward to working with the FDA to bring this important breakthrough therapy to patients as soon as possible.

CHRONOS 研究的一年結果進一步表明，度普利尤單抗可影響白血球介素 4-13 路徑的異常激活，並產生顯著療效，且沒有與免疫抑制療法相關的副作用。在這方面，非常重要的一點是，到目前為止，我們的異位性皮膚炎治療計畫中還沒有觀察到整體感染或嚴重感染的增加。美國生物製品許可申請已完成，我們期待與FDA合作，盡快將這項重要的突破性療法帶給患者。

We are also developing dupilumab in other allergic diseases, such as asthma, nasal polyps, and eosinophilic esophagitis. As a reminder, our first pivotal study in asthma showed that two doses of dupilumab, 200-milligram and 300-milligram every other week, in combination with inhaled steroids and long-acting beta agonists, demonstrated a statistically significant 12% to 15% improvement in lung function as measured by FEV-1 over placebo at week 12, and a 64% to 75% reduction in the annualized rate of severe asthma exacerbations over placebo.

我們也正在開發度普利尤單抗用於治療其他過敏性疾病，例如氣喘、鼻息肉和嗜酸性食道炎。提醒一下，我們首個氣喘關鍵性研究表明，每隔一周給予兩劑度普利尤單抗（200毫克和300毫克），並聯合吸入性糖皮質激素和長效β受體激動劑，在第12週時，肺功能（以FEV-1衡量）較舊安慰劑組有統計學意義中顯著的年齡改善至12%至15%，嚴重哮喘發作的年急性發生率5%。

The most common adverse event was injection site reaction, which was more frequent in the dupilumab dose groups at 13% to 25%, compared to 12% in the placebo group. The incidence of infections was balanced across treatment groups at 42% to 45% in dupilumab arms and 46% in the placebo arm, as was the incidence of serious adverse events, which were seen in3% to 7% of the dupilumab groups and 5% in the placebo group.

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，度普利尤單抗組為 42% 至 45%，安慰劑組為 46%；嚴重不良事件的發生率也較為均衡，度普利尤單抗組為 3% 至 7%，安慰劑組為 5%。

We expect our confirmatory one-year Phase 3 study of dupilumab in this indication to complete enrollment in the third quarter of 2016. As a reminder, we are the only late stage biologic that targets both IL-4 and IL-13, and recent competitor developments in the late stage asthma space are consistent with our preclinical data and our hypotheses that it is important to block both of these interleukins.

我們預計，針對此適應症的 dupilumab 的為期一年的 3 期確證性研究將於 2016 年第三季完成入組。需要提醒的是，我們是唯一一家針對 IL-4 和 IL-13 的後期生物製劑公司，而近期競爭對手在後期氣喘領域的進展與我們的臨床前數據和假設相符，即阻斷這兩種白細胞介素非常重要。

Turning to Praluent. Our 18,000-patient ODYSSEY outcome study is ongoing. As we have previously disclosed, the Data Monitoring Committee for this study completed the first interim analysis when 50% of the total events had accrued, based on unblinded study data. In addition to reviewing the safety study, the DMC performed a futility assessment and recommended that the study continue with no changes. A second interim analysis for futility, as well as for overall efficacy, when 75% of the targeted primary events has occurred is expected later this year.

轉向Praluent。我們正在進行一項針對 18,000 名患者的 ODYSSEY 結果研究。正如我們之前所揭露的那樣，本研究的數據監測委員會在總事件數達到 50% 時，根據非盲研究數據完成了第一次中期分析。除了審查安全性研究外，資料監測委員會還進行了無效性評估，並建議繼續進行研究，不做任何更改。預計今年晚些時候，當 75% 的目標主要事件發生時，將進行第二次中期分析，評估療效（包括無效性和整體療效）。

As Len mentioned, we also have three other late stage programs, sarilumab, our interleukin 6 receptor antibody for rheumatoid arthritis, where we expect FDA action by October 30; fasinumab, our NGF antibody for pain associated with osteoarthritis; and Regeneron 2222 for respiratory syncytial virus, or RSV.

正如 Len 所提到的，我們還有三個後期項目：sarilumab，一種用於治療類風濕性關節炎的白細胞介素 6 受體抗體，我們預計 FDA 將於 10 月 30 日前採取行動；fasinumab，一種用於治療骨關節炎相關疼痛的 NGF 抗體；以及 Regeneron 2222，用於治療呼吸道合胞病毒 (RSV)。

Turning now to our earlier stage pipeline. In May, we reported positive interim proof of concept data from a Phase 2 study of evinacumab, an antibody to angiopoietin PTL3 in patients with a homozygous form of familial hypercholesterolemia. These patients continue to have a major unmet need, as they are typically not as responsive to standard lipid lowering therapy, such as statins, or even to PCSK9 inhibition. And some of the other treatment options available to them are limited by the accompanying safety and tolerability concerns.

現在讓我們來看看我們早期階段的流程。5 月，我們發表了 evinacumab（一種針對血管生成素 PTL3 的抗體）在純合子家族性高膽固醇血症患者的 2 期研究中取得的積極中期概念驗證數據。這些患者仍有重大未滿足的需求，因為他們通常對標準降血脂療法（如他汀類藥物）甚至 PCSK9 抑制劑的反應都不太好。而其他一些可供選擇的治療方案則受到安全性和耐受性問題的限制。

Although these data were from a small number of patients, we are encouraged by the additional 55% reduction in LDL cholesterol levels at week 4 on top of standard of care compared to baseline. In this study, evinacumab was generally well tolerated and there were no adverse events leading to discontinuation. The most common drug-related adverse events were injection site reactions, which were mild in severity.

儘管這些數據來自少數患者，但與基線相比，在第 4 週標準治療的基礎上，低密度脂蛋白膽固醇水平額外降低了 55%，這令我們感到鼓舞。在本研究中，evinacumab 的耐受性總體良好，沒有發生導致停藥的不良事件。最常見的藥物相關不良反應是注射部位反應，但程度較輕。

Our Phase 2 study of EYLEA in a co-formulated combination with [rinucumab], our PDGF receptor antibody, in wet age-related macular degeneration, or wet AMD, which has been granted fast track designation, is fully enrolled and we expect top line data from this study in the fourth quarter of 2016. This is a three-arm, two-stage study with patients randomized to receive one of three dosing regimens, EYLEA alone, EYLEA in combination with low dose PDGF blocking antibody, or EYLEA in combination with high dose PDGF blocking antibody.

我們正在進行 EYLEA 與我們的 PDGF 受體抗體 [rinucumab] 聯合用藥治療濕性老年性黃斑部病變（濕性 AMD）的 II 期研究，該研究已獲得快速通道資格，目前已完成全部受試者招募，我們預計將於 2016 年第四季度獲得該研究的主要數據。這是一項三臂兩階段研究，患者被隨機分配接受三種給藥方案之一：單獨使用 EYLEA、EYLEA 與低劑量 PDGF 阻斷抗體聯合使用，或 EYLEA 與高劑量 PDGF 阻斷抗體聯合使用。

The primary efficacy endpoint of the first stage of this study is the mean change in visual acuity at week 12 from baseline. The second stage of the study is designed to confirm and extend the findings from the first stage of the study.

本研究第一階段的主要療效終點是第 12 週視力較基線的平均變化。研究的第二階段旨在確認和擴展第一階段的研究結果。

Our Phase 2 combination studies of EYLEA in a co-formulated combination with nesvacumab, our antibody to angiopoietin 2 in AMD and DME, continue to enroll patients. We are very excited by our earlier stage pipeline in immuno oncology, where both our PD-1 antibody and our CD-20 by CD-3 by specific antibodies have demonstrated promising activity in early clinical trials. Our potentially pivotal study with our PD-1 antibody in cutaneous squamous cell carcinoma continues to enroll patients and we hope to be investigating additional agents and combinations over the next 6 to 12 months.

我們正在繼續進行 EYLEA 與 nesvacumab（一種針對 AMD 和 DME 的血管生成素 2 的抗體）聯合用藥的 2 期聯合研究，招募患者。我們對免疫腫瘤學早期研發管線感到非常興奮，我們的 PD-1 抗體和 CD-20 by CD-3 by 特異性抗體在早期臨床試驗中均表現出了良好的活性。我們正在進行一項可能具有決定性意義的研究，該研究使用我們的 PD-1 抗體治療皮膚鱗狀細胞癌，目前仍在招募患者，我們希望在接下來的 6 到 12 個月內研究其他藥物和組合療法。

We have also expanded our capability in the area of precision immunotherapy, with our recently announced collaboration with Adicet, which will allow us to discover and develop engineered next generation immune cell therapies. This collaboration takes advantage of our unique VelocImmune and Veloci-Next technologies that will allow us to use cell-based therapies to target tumor cells.

我們也擴大了在精準免疫療法領域的能力，最近宣布與 Adicet 合作，這將使我們能夠發現和開發工程化的下一代免疫細胞療法。此次合作將利用我們獨特的 VelocImmune 和 Veloci-Next 技術，使我們能夠使用基於細胞的療法來靶向腫瘤細胞。

We also recently initiated a Phase 1 study in healthy volunteers of Regeneron 2477, an activin antibody being developed for the treatment of Fibrodysplasia ossificans progressiva, or FOP, and other musculoskeletal disorders.

我們最近也啟動了 Regeneron 2477 的 1 期臨床試驗，該藥物是一種激活素抗體，正在開髮用於治療進行性骨化性纖維發育不良症 (FOP) 和其他肌肉骨骼疾病。

We remain committed to using our technologies and approaches to help address emerging infectious diseases, such as Ebola, MERS, and Zika. For Zika, we have identified several fully human monoclonal antibody candidates that are able to potentially block the virus -- to potently block the virus from infecting cells in vitro, and early data indicate that these antibodies are protective in an animal model. We are now in the process of scaling up for human trials. We also recently initiated our first in human study in healthy volunteers in our Ebola program, which has been granted orphan drug designation by the FDA.

我們將繼續致力於運用我們的技術和方法來幫助應對新出現的傳染病，例如伊波拉病毒、中東呼吸綜合症病毒和寨卡病毒。針對寨卡病毒，我們已經確定了幾種能夠有效阻斷病毒的全人源單株抗體候選藥物—能夠有效阻止病毒在體外感染細胞，早期數據顯示這些抗體在動物模型中具有保護作用。我們目前正在擴大規模，準備進行人體試驗。我們最近也在伊波拉計畫中啟動了首次針對健康志願者的人體研究，該計畫已獲得美國食品藥物管理局 (FDA) 的孤兒藥資格認定。

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

那麼，現在讓我把電話交給鮑伯·特里費。

Thank you, George, and hello, everyone. We're pleased with the sales growth of EYLEA, or aflibercept injection, both in the United States and ex-US in the first half of 2016. We've made progress in improving access and reimbursement for Praluent, or alorocumab, among US payers. In addition, the European and Japanese launches for Praluent continue to progress, and we are now preparing for the potential US launches of sirilumab and dupilumab over the next year.

謝謝你，喬治，大家好。我們對 EYLEA（阿柏西普注射液）在 2016 年上半年在美國和美國以外地區的銷售成長感到滿意。我們在改善美國支付方獲得 Praluent（或稱為 alorocumab）的途徑和報銷方面取得了進展。此外，Praluent 在歐洲和日本的上市計劃繼續推進，我們現在正為明年在美國推出 sirilumab 和 dupilumab 做準備。

Starting with EYLEA, second quarter US net sales grew 27% year-over-year. Net US EYLEA sales in the second quarter were $831 million. Net ex-US EYLEA sales in the second quarter were $486 million, which represents 44% growth year-over-year on a reported basis.

以安樂為例，第二季美國淨銷售額年增 27%。安理國際第二季在美國的淨銷售額為 8.31 億美元。安樂第二季度除美國以外淨銷售額為 4.86 億美元，以報告數據計算年增 44%。

We continue to have a strong position in our US market share leadership for EYLEA in the FDA approved anti-VEGF market in terms of injections, as reported by 203 retinal specialists in our quarterly market research survey. According to our survey results, in the overall anti-VEGF market, EYLEA has a 37% share of injections, as compared to 19% for ranibizumab and 44% for off-label repackaged bevacizumab. On the other hand, with our growing market share, our expenses to support reimbursement activities, including patient support services and reimbursement assistance, have also increased, impacting both our gross to net ratio, as well as our profit margins.

根據我們季度市場調查中 203 位視網膜專家的報告，我們在 FDA 批准的抗 VEGF 注射劑市場中，EYLEA 在美國市場份額方面繼續保持領先地位。根據我們的調查結果，在整個抗 VEGF 市場中，EYLEA 注射劑的市佔率為 37%，而雷珠單抗的市佔率為 19%，非適應症重新包裝的貝伐珠單抗的市佔率為 44%。另一方面，隨著市場份額的成長，我們用於支持報銷活動（包括患者支持服務和報銷援助）的費用也隨之增加，這影響了我們的毛利淨利比率和利潤率。

I should note that there are currently a series of proposals from the Centers for Medicare and Medicaid Services regarding physician reimbursement for physician administered Medicare Part B buy-and-bill drugs, which could lead towards physicians favoring the use of bevacizumab or, in large volume retinal practices, ranibizumab, due to the provision of increased direct-to-physician financial incentives from the manufacturer and group purchasing organizations. The impact of any changes is difficult to predict, though we are monitoring the situation very closely.

我應該指出，目前醫療保險和醫療補助服務中心提出了一系列關於醫生對醫生管理的醫療保險 B 部分購買和結算藥物的報銷提案，這可能會導致醫生傾向於使用貝伐單抗，或者在視網膜疾病治療量大的診所中使用雷珠單抗，因為製造商和集團採購組織會向醫生提供更多的直接經濟激勵。任何變化的影響都難以預測，但我們正在密切關注事態發展。

Regeneron believes that EYLEA is clearly differentiated from both bevacizumab and ranibizumab. Physicians and patients should not be denied access to any drug therapy that is deemed appropriate. We believe that physician choice should be preserved and alternative schemas to reduce healthcare costs should be explored.

再生元公司認為，EYLEA 與貝伐單抗和雷珠單抗都有明顯的差異。醫生和患者不應被剝奪獲得任何被認為合適的藥物治療的權利。我們認為應該保留醫師的選擇權，並應探索降低醫療成本的替代方案。

Turning now to Praluent. As reported by Sanofi, net sales in the second quarter were $24 million worldwide, with the US accounting for $21 million of the total. I'm pleased to share that as of July 1, approximately 74% of commercially insured lives and approximately 91% of Medicare insured lives have access to Praluent.

現在轉向Praluent。根據賽諾菲公司報告，第二季全球淨銷售額為 2,400 萬美元，其中美國市場貢獻了 2,100 萬美元。我很高興地告訴大家，截至 7 月 1 日，約 74% 的商業保險投保人和約 91% 的聯邦醫療保險投保人可以使用 Praluent。

We continue to see improvement in the number of prescriptions that are successfully being filled. With both Praluent and evolocumab generally splitting market share evenly; however, only approximately 25% of our prescriptions written actually get dispensed. Unfortunately, due to unprecedented strict utilization management criteria and very tedious prior authorization paperwork that the pharmacy benefits managers at health plans have put in place, many patients who are eligible for treatment with a PCSK9 inhibitor have not had their prescriptions filled.

我們看到處方成功配藥的數量持續增加。Praluent 和 evolocumab 的市佔率大致相當；然而，我們開出的處方中只有大約 25% 最終被配發。不幸的是，由於醫療計劃的藥房福利管理機構實施了前所未有的嚴格用藥管理標準和非常繁瑣的事先授權文件，許多符合 PCSK9 抑制劑治療條件的患者沒有拿到處方藥。

We continue to focus our efforts on improving access -- or improving the prescription process through the payers and the specialty pharmacies. Over the last several months, we've seen some payers loosen their utilization management criteria, removing a requirement for prior ezetimide therapy. Others have streamlined the prior authorization processes. ODYSSEY outcomes data, if positive, are anticipated to be a key driver in shaping the future success of Praluent.

我們將繼續致力於改善醫療服務取得途徑——或者說，透過支付方和專科藥局來改善處方流程。在過去的幾個月裡，我們看到一些支付方放寬了他們的用藥管理標準，取消了先前接受依澤替米特治療的要求。其他機構則簡化了事先授權流程。如果 ODYSSEY 的結果數據是正面的，預計將成為塑造 Praluent 未來成功的關鍵驅動因素。

Outside of the United States, Praluent was approved in the EU in September of 2015, with the product now available in several countries. Reimbursement discussions are currently underway with several governments across Europe. Positive reimbursement decisions have been issued in the UK and Spain, among others. It still remains a difficult reimbursement market, with some countries awaiting outcomes data.

在美國以外，Praluent 於 2015 年 9 月在歐盟獲得批准，目前該產品已在多個國家上市。目前正與歐洲多個國家的政府就報銷事宜進行磋商。英國和西班牙等國已作出積極的報銷決定。健保報銷市場依然困難重重，一些國家仍在等待結果數據。

In the United States, we've submitted the supplemental BLA for the 300-milligram monthly dose of Praluent and have been granted a PDUFA date of January 24, 2017. We have also submitted a regulatory application for Praluent monthly dosing in the EU. Also, in July, Praluent was approved in Japan.

在美國，我們已提交了 Praluent 300 毫克每月劑量的補充生物製品許可申請 (BLA)，並已獲得 2017 年 1 月 24 日的 PDUFA 日期。我們也向歐盟提交了 Praluent 每月給藥的監管申請。此外，Praluent 於 7 月在日本獲得批准。

We've submitted a BLA to the US Food and Drug Administration for sarilumab, our IL-6 receptor inhibitor for rheumatoid arthritis, and have been granted a PDUFA date of October 30, 2016. Earlier this week, the European Marketing Authorization Application, or MAA, for sarilumab was accepted for review by the European Medicines Agency.

我們已向美國食品藥物管理局提交了 sarilumab（一種用於治療類風濕性關節炎的 IL-6 受體抑制劑）的生物製品許可申請 (BLA)，並已獲得 2016 年 10 月 30 日的 PDUFA 批准日期。本週早些時候，歐洲藥品管理局受理了 sarilumab 的歐洲上市許可申請 (MAA) 進行審查。

We will be co-promoting sarilumab with Sanofi Genzyme in the United States, and we have completed hiring of our field-based team. Training began this week. Co-promotion decisions for other countries will be made over time.

我們將與賽諾菲健贊在美國共同推廣 sarilumab，並且我們已經完成了現場團隊的招募。訓練本週開始。與其他國家聯合推廣的決定將視情況而定。

We are currently preparing for dupilumab commercialization with a potential US approval in the first half of 2017. We'll be co-promoting dupilumab in the United States with Sanofi Genzyme and have begun interviewing our sales management team. Co-promotion decisions for other countries will be made at a later date.

我們目前正在為度普利尤單抗的商業化做準備，預計在 2017 年上半年獲得美國批准。我們將與賽諾菲健贊在美國共同推廣度普利尤單抗，並且已經開始面試我們的銷售管理團隊。其他國家的聯合推廣決定將在稍後做出。

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 to everyone. I have several financial updates to provide this morning.

謝謝你，鮑勃，大家早安。今天早上我有一些財務方面的最新情況要向大家報告。

Let me start with our top line second quarter earnings. In the second quarter of 2016, non-GAAP net income per diluted share was $2.82. This represented an increase of 24% in both non-GAAP net income per diluted share, as well as non-GAAP net income in the second quarter of 2016 compared to the second quarter of 2015.

首先，讓我來看看我們第二季的主要獲利情況。2016 年第二季度，非 GAAP 每股攤薄淨收入為 2.82 美元。與 2015 年第二季相比，2016 年第二季非 GAAP 每股稀釋淨收入和非 GAAP 淨收入均成長了 24%。

Regeneron's second quarter 2016 non-GAAP net income excludes non-cash share-based compensation expense and the $75 million upfront payment made in connection with our April, 2016 license and collaboration agreement with Intellia. It also includes the income tax effect of these non-GAAP adjustments. A full reconciliation of GAAP to non-GAAP earnings is set forth in our earnings release. I will describe in further detail shortly, effective this quarter, our non-GAAP net income is no longer includes an adjustment from GAAP tax expense to the amount of taxes that were estimated to be paid or payable in cash.

Regeneron 2016 年第二季非 GAAP 淨收入不包括非現金股份支付費用以及根據我們 2016 年 4 月與 Intellia 達成的許可和合作協議支付的 7,500 萬美元預付款。它還包括這些非GAAP調整的所得稅影響。我們的獲利報告中列出了 GAAP 收益與非 GAAP 收益的完整調整表。稍後我將更詳細地說明，從本季度開始，我們的非GAAP淨收入不再包括從GAAP稅收費用到預計以現金支付或應付的稅款金額的調整。

Total revenues in the second quarter of 2016 were $1.2 billion, which represented a year-over-year growth of 21% over the second quarter of 2015. Net product sales were $834 million in the second quarter of 2016, compared to $658 million in the second quarter of 2015.

2016 年第二季總營收為 12 億美元，比 2015 年第二季年增 21%。2016 年第二季淨產品銷售額為 8.34 億美元，而 2015 年第二季為 6.58 億美元。

EYLEA US net product sales were $831 million, compared to $655 million in the second quarter of 2015, representing a 27% year-over-year growth, sequential quarter-over-quarter growth was 6%. EYLEA distributor inventory levels continue to be within our normal one- to two-week targeted range, and the June 30 levels were very similar to our March 31, 2016 levels. Please note that we are reaffirming our 2016 US EYLEA net sales guidance to be year-over-year growth of between 20% and 25%.

EYLEA 美國淨產品銷售額為 8.31 億美元，而 2015 年第二季為 6.55 億美元，年成長 27%，較上季成長 6%。EYLEA 經銷商的庫存水準繼續保持在我們正常的一到兩週的目標範圍內，6 月 30 日的庫存水準與 2016 年 3 月 31 日的庫存水準非常相似。請注意，我們重申 2016 年美國安樂淨銷售額預期，即年增 20% 至 25%。

Ex-US EYLEA sales, where product revenue is recorded by our collaborator, Bayer, were $486 million in the second quarter of 2016, compared to $338 million in the second quarter of 2015, representing a 44% increase on a reported basis. On an operational basis, or constant currency basis, sales increased approximately 42%.

2016 年第二季度，EYLEA 在美國以外的銷售額（產品收入由我們的合作夥伴拜耳公司記錄）為 4.86 億美元，而 2015 年第二季度為 3.38 億美元，按報告數據計算增長了 44%。以營運成本或固定匯率計算，銷售額成長約 42%。

In the second quarter of 2016, Regeneron recognized $167 million from our share of net profits from EYLEA sales outside the US. Total Bayer collaboration revenue for the second quarter of 2016 was $192 million.

2016 年第二季度，Regeneron 從美國以外地區 EYLEA 的銷售淨利潤中確認了 1.67 億美元。2016 年第二季拜耳合作總營收為 1.92 億美元。

As a reminder, for the EYLEA franchise, during May, 2016 we stopped incurring the royalty expense in commence with our agreement with Genentech related to global EYLEA sales. This benefited our cost of goods sold and cost of collaboration manufacturing line items.

再次提醒，對於 EYLEA 特許經營權，自 2016 年 5 月起，我們停止支付特許權使用費，開始履行與 Genentech 就 EYLEA 全球銷售達成的協議。這有利於降低我們的銷售成本和合作生產成本。

Turning now to our Sanofi collaboration, total Sanofi collaboration revenue was $163 million for the second quarter of 2016. Sanofi collaboration revenue line primarily consists of reimbursement of Regeneron incurred R&D expenses, reimbursement of Regeneron commercialization related expenses, and our share of profits or losses in connection with commercialization of antibodies.

現在來說說我們與賽諾菲的合作，2016 年第二季賽諾菲合作的總收入為 1.63 億美元。賽諾菲的合作收入主要包括：報銷 Regeneron 發生的研發費用、報銷 Regeneron 的商業化相關費用，以及我們與抗體商業化相關的利潤或虧損份額。

In the second quarter of 2016, our share of the collaborations losses in connection with commercialization of antibodies, primarily Praluent, was $122 million, which can be found in table 4 of our earnings release. Netted within the collaboration losses were the global sales of Praluent as recognized by our collaborator, Sanofi, of $24 million for the second quarter of 2016.

2016 年第二季度，我們在抗體商業化合作中承擔的損失份額（主要是 Praluent）為 1.22 億美元，詳情請參閱我們的收益報告表 4。合作損失中包括我們的合作夥伴賽諾菲確認的 Praluent 2016 年第二季全球銷售額 2,400 萬美元。

Turning now to expenses. Non-GAAP R&D expense was $406 million for the second quarter of 2016. Our non-GAAP unreimbursed R&D expense, which is calculated as the total GAAP R&D expense less R&D reimbursements from our collaborators, R&D non-cash share-based compensation expense, and the Intellia upfront payment, was $222 million for the three months ended June 30, 2016. Our press release includes all the information that is required to calculate unreimbursed non-GAAP R&D expense.

接下來談談費用。2016 年第二季非 GAAP 研發費用為 4.06 億美元。截至 2016 年 6 月 30 日止的三個月，我們的非 GAAP 未報銷研發費用（計算方法為：GAAP 研發費用總額減去合作方的研發報銷款、研發非現金股份支付費用以及 Intellia 預付款）為 2.22 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。

Given our forecasted spend and associated reimbursement level for the second half of 2016, we are increasing and tightening our full-year guidance for non-GAAP unreimbursed R&D to be in the range of between $970 million to just over $1 billion, from the previously provided range of $875 million to $950 million.

鑑於我們對 2016 年下半年的支出和相關報銷水準的預測，我們將全年非 GAAP 未報銷研發支出的指導範圍從先前提供的 8.75 億美元至 9.5 億美元提高並收緊，使其在 9.7 億美元至略高於 10 億美元之間。

This increase is a result of two factors, a forecasted increase in spending shift from partner to unpartnered antibody development programs. We now have seven antibodies that we are developing independently including two that are in late stage, RSV and fasinumab. And a greater allocation of unreimbursed manufacturing costs within our Rensselaer, New York facility to R&D as opposed to inventory, due to less demand for Praluent than was anticipated.

這一增長是兩個因素造成的，一是預計支出增加，二是抗體開發項目從合作項目轉向非合作項目。我們目前有七種抗體正在獨立研發，其中兩種已進入後期階段，分別是 RSV 和 fasinumab。由於 Praluent 的需求低於預期，我們在紐約州倫斯勒工廠將未報銷的製造成本更多地分配給了研發，而不是庫存。

Non-GAAP SG&A expense was $244 million for the second quarter of 2016. We are increasing and tightening non-GAAP SG&A expense in 2016 to $980 million to $1.02 billion, from the range of $925 million to $1 billion. This increase is primarily driven by our expenses to support EYLEA reimbursement activities, including patient support services and reimbursement assistance, along with additional investments in EYLEA's commercialization. This increases is partially offset by lower commercialization and pre-launch spend associated with our collaboration antibodies with Sanofi.

2016 年第二季非 GAAP 銷售、一般及行政費用為 2.44 億美元。我們將 2016 年的非 GAAP 銷售、一般及行政費用從 9.25 億美元至 10 億美元區間增加並收緊至 9.8 億美元至 10.2 億美元區間。這一增長主要是由於我們為支持 EYLEA 報銷活動而增加的支出，包括患者支持服務和報銷援助，以及對 EYLEA 商業化的額外投資。這一成長部分被與賽諾菲合作研發的抗體相關的商業化和上市前支出減少所抵消。

As you may recall, last quarter we introduced a new guidance component, Sanofi reimbursement of Regeneron commercialization-related expenses, which represents reimbursement of internal and external costs that Regeneron incurs in connection with preparing to commercialize, or commercializing, as applicable, Praluent, sarilumab and dupilumab. Again, this is the line item found within Sanofi collaboration revenue and is referenced in table 4 of our press release.

您可能還記得，上個季度我們引入了一個新的指導組成部分，即賽諾菲對 Regeneron 商業化相關費用的報銷，該報銷代表 Regeneron 在準備商業化或商業化 Praluent、sarilumab 和 dupilumab（如適用）過程中產生的內部和外部成本。同樣，這是賽諾菲合作收入中的一個項目，在我們的新聞稿表 4 中有所提及。

For the second quarter of 2016, the reimbursement of Regeneron commercialization-related expenses was $86 million. We are lowering and tightening this guidance in 2016 to be in the range of $310 million and $340 million, from $320 million to $370 million.

2016 年第二季度，Regeneron 商業化相關費用的報銷金額為 8,600 萬美元。我們將 2016 年的業績預期下調並收緊至 3.1 億美元至 3.4 億美元之間，此前預期為 3.2 億美元至 3.7 億美元。

Turning now to taxes. Prior to the quarter ended June 30, 2016, our non-GAAP measures included an income tax expense adjustment from GAAP tax expense to the amount of taxes that were paid or payable in cash for the respective period. Historically, there was a significant difference between the Company's GAAP effective tax rate and the actual cash income taxes paid or payable, primarily due to tax benefits related to employee exercises of stock options. The tax benefits related to employee exercises of stock options were historically recorded in additional paid-in capital for GAAP reporting purposes.

接下來談談稅務問題。在截至 2016 年 6 月 30 日的季度之前，我們的非 GAAP 指標包括將 GAAP 稅金調整為相應期間以現金支付或應付的稅款金額的所得稅費用。從歷史上看，公司 GAAP 有效稅率與實際支付或應付的現金所得稅之間存在顯著差異，這主要是由於與員工行使股票選擇權相關的稅收優惠。根據美國通用會計準則 (GAAP) 的報告要求，員工行使股票選擇權所獲得的稅務優惠歷來都計入額外實收資本。

During the second quarter of 2016, the Company early adopted Accounting Standards update 2016-09. The new standard requires companies to recognize tax benefits in connection with employee exercises of stock options in the income statement. In other words, we will account for tax deductions related to stock option exercises in the period of exercise as a discrete item to the quarter. With the early adoption of the new standard, the Company chose to discontinue its former non-GAAP income tax expense adjustment since, by adopting the new standard, it eliminated one of our primary differences between the Company's effective tax rate and cash income taxes paid or payable.

2016 年第二季度，公司提前採用了 2016-09 號會計準則更新。新準則要求公司在損益表中確認與員工行使股票選擇權相關的稅務優惠。換句話說，我們將把與股票選擇權行使相關的稅收扣除額在行使期間作為季度的一個單獨項目進行核算。由於新準則的提前採用，公司選擇停止其先前的非GAAP所得稅費用調整，因為採用新準則消除了公司實際稅率與已付或應付現金所得稅之間的主要差異之一。

As a result, our second quarter 2016, and 2015 non-GAAP financial results included in our earnings release for comparison, now reflect this continuance of our non-GAAP income tax expense adjustment. This new standard will result in variability in our effective tax rate from quarter to quarter, as based on GAAP rules these items are not forecasted in our estimated annual effective tax rate. These deductions are based on the Company's stock price and individual employees' decisions on when to exercise their stock options.

因此，我們在收益報告中納入的 2016 年第二季度和 2015 年非 GAAP 財務業績（用於比較）現在反映了我們繼續進行非 GAAP 所得稅費用調整。根據 GAAP 規則，這些項目並未納入我們預期的年度實際稅率，因此，這項新標準將導致我們的實際稅率逐季波動。這些扣款是根據公司股價和員工何時行使股票選擇權的決定而定的。

The current tax-related adjustment in our reconciliation of GAAP net income to non-GAAP net income (Technical Difficulties) table 3 of our earnings release solely represents the income tax effects related to our non-GAAP pretax adjustment.

我們獲利報告中 GAAP 淨收入與非 GAAP 淨收入調節表（技術困難）第 3 表中目前的稅務相關調整僅代表與非 GAAP 稅前調整相關的所得稅影響。

Our effective tax rate for the second quarter of 2016 was approximately 33%, which is 8% lower compared to the second quarter of 2015. This decrease was primarily due to the impact of changes in the geographic mix of earnings and share-based compensation as compared to the same quarter of last year. For 2016, our guidance for our GAAP effective tax rate for the full year will be 33% to 41%.

2016 年第二季的實際稅率約為 33%，比 2015 年第二季下降了 8%。與去年同期相比，這一下降主要是由於收益和股權激勵的地域組成發生變化所致。2016 年全年，我們預計 GAAP 有效稅率為 33% 至 41%。

Our capital expenditures for the second quarter of 2016 and for the six months ended June 30, 2016 were $139 million and $243 million, respectively. We are lowering our full-year 2016 capital expenditure guidance to a range of $480 million to $530 million, from the previously provided range of $550 million to $625 million. These 2016 expenditures include the expansion of our manufacturing capabilities in both Rensselaer, New York and Limerick, Ireland, as well as growth in our Tarrytown, New York headquarters, as we continue to grow our employee base.

2016 年第二季和截至 2016 年 6 月 30 日的六個月期間，我們的資本支出分別為 1.39 億美元和 2.43 億美元。我們將 2016 年全年資本支出預期從先前給出的 5.5 億美元至 6.25 億美元下調至 4.8 億美元至 5.3 億美元。2016 年的這些支出包括擴大我們在紐約州倫斯勒和愛爾蘭利默里克的生產能力，以及擴大我們在紐約州塔里敦的總部規模，同時我們也不斷擴大我們的員工隊伍。

Regeneron's balance sheet had $1.64 billion of cash and marketable securities as of June 30, 2016. Less than $500,000 of our originally issued $400 million of convertible senior notes due October 1, 2016 remain outstanding.

截至 2016 年 6 月 30 日，Regeneron 的資產負債表顯示其擁有 16.4 億美元的現金和有價證券。在我們最初發行的 4 億美元可轉換優先票據（2016 年 10 月 1 日到期）中，目前未償還的不足 50 萬美元。

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

那麼，現在我想把電話轉回給麥可。

Thank you, Bob. That concludes our prepared remarks. We'd now like to open the call for Q&A.

謝謝你，鮑伯。我們的發言稿到此結束。現在我們開始問答環節。

As we'd like to give as many people a chance to ask questions as possible, as always, please limit yourself to one question. Our team will be available in our office after the call for any follow-up questions. Operator, if you can now open the call for questions.

為了讓盡可能多的人有機會提問，和往常一樣，請每人只提一個問題。通話結束後，我們的團隊將在辦公室為您解答任何後續問題。操作員，現在可以開始接受提問了嗎？

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

謝謝。現在開始問答環節。

(Operator Instructions)

（操作說明）

Our first question comes from Terence Flynn from Goldman Sachs.

我們的第一個問題來自高盛的 Terence Flynn。

Hello. That is Cameron Bradshaw filling in for Terence. Thank you for taking our question. I was wondering, for the Phase 2 trials, EYLEA combined with your PDGF, looks like we're going to see in the data in the second half of this year. Can you just remind us of the trial design and then what you're hoping to see with the respect to efficacy in order to make a go, no go decision on the Phase 3? Thank you.

你好。那是卡梅倫·布拉德肖代替特倫斯上場。感謝您回答我們的問題。我想知道，在二期臨床試驗中，EYLEA 與你們的 PDGF 聯合使用，看起來我們將在今年下半年的數據中看到結果。您能否簡要介紹試驗設計，以及您希望在療效方面看到什麼，以便決定是否進行 3 期臨床試驗？謝謝。

This is George. The study design really has two stages. The first is a head-to-head-to-head between the three groups that we described in our call, the combination of the PDGF blocker on top of EYLEA, versus EYLEA alone with two doses of the blocker. That's the first stage.

這是喬治。研究設計其實分為兩個階段。首先是我們在電話會議中描述的三個組別之間的直接比較，即在 EYLEA 的基礎上聯合使用 PDGF 阻斷劑，與單獨使用 EYLEA 並配合兩劑阻斷劑進行比較。這是第一階段。

As you know, even in studies with hundreds of patients in them, as we've of course seen, we have as much experience as anybody alone and with our collaborators in doing these large studies, there can be a lot of variability in letters gained. So we designed the study to include a second stage, as well, that actually shows the effects of adding on therapy on top within the same groups. That, we predict, to be a more powerful way of confirming if there are added benefits of the PDGF therapy.

如您所知，即使在有數百名患者參與的研究中，正如我們當然已經看到的，我們和我們的合作者在進行這些大型研究方面擁有與任何人一樣豐富的經驗，但獲得的信件數量也可能存在很大的差異。因此，我們設計了這項研究，使其包含第二階段，以實際展示在同一組人群中增加治療的​​效果。我們預測，這將是確認 PDGF 療法是否具有額外益處的更有效方法。

So we will have the first type of comparison, which we consider perhaps to be slightly less powerful, in the time frame that I just described; and then we will also be getting the second stage of data. So depending on how strong the first set of data is, we will either be able to make a decision at that point or we'll be awaiting the results from the second stage to help us make that decision.

因此，我們將進行第一種比較，我們認為這種比較可能效力稍弱一些，時間範圍正如我剛才所描述的；然後我們還將獲得第二階段的數據。因此，根據第一組資料的可靠性，我們要麼能夠當場做出決定，要麼需要等待第二階段的結果來幫助我們做出決定。

I would just add, in terms of helping you think about it, for us, since this is a single injection of the two antibodies by the physician, that we don't have to have a gigantic benefit. We just have to have something that's clearly beneficial. Because the hurdle for us to move forward isn't that great, because there's no additional burden on patients having to take an additional injection.

我還要補充一點，為了幫助大家思考，對我們來說，由於醫生只需注射一次這兩種抗體，我們就不必指望獲得巨大的益處。我們只需要一些明顯有益的東西。因為我們前進的障礙並不大，因為患者無需額外注射，不會增加額外的負擔。

Great. Next question.

偉大的。下一個問題。

Thank you.

謝謝。

Our next question comes from Robyn Karnauskas from Citigroup.

下一個問題來自花旗集團的 Robyn Karnauskas。

Hello, guys. Thank you. You mentioned that access is opening up a little bit for the PCSK9s. Can you talk a little about what percentage of the payers had higher restrictions initially this year and then how did that change, what percentage of people are not requiring prior auth or reduced the requirements for filling out forms, et cetera?

大家好。謝謝。您提到 PCSK9 的准入條件正在逐步開放。您能否談談今年初期付款方的限制較多的百分比，以及後來情況發生了怎樣的變化，有多少百分比的人不再需要事先授權或減少了填寫表格的要求等等？

And then going to that, what do you think the trigger point was for doing that? And what are the timing for these events? Is it third quarter? What triggers these things and how do we think about that going forward? Thank you.

那麼，你認為引發這件事的觸發點是什麼？這些活動的具體時間安排是怎麼樣的？現在是第三季嗎？是什麼引發了這些現象？我們今後該如何看待這個問題？謝謝。

So there have been some payers that based upon the FDA decision not to approve ezetimibe based upon their outcomes data that have said since ezetimibe does not have an FDA indication for the prevention of cardiovascular outcomes, that on their own, or at the advice of some of their physician medical directors, they've removed the ezetimibe step edit. And that has happened in a few plans already.

因此，一些支付方根據 FDA 的決定，基於其結果數據不批准依折麥布，並表示由於依折麥布沒有 FDA 批准用於預防心血管疾病，他們自行或在一些醫生醫療總監的建議下，取消了對依折麥布的階梯式編輯。這種情況已經在一些方案中出現了。

With regards to the prior authorization paperwork, some of the payers had prior authorizations that required tens, or almost up to 40 questions. It became very tedious for the physician.

關於事先授權文件，一些付款方的事先授權需要填寫數十個，甚至近 40 個問題。這讓醫生感到非常厭煩。

So some of the plans have begun to change their prior authorization to be simpler. And again, that is in place in a few payers now. I think the real driver that's going to change things is going to be when we get the outcomes data for the product.

因此，一些計劃已經開始簡化事先審批流程。而且，目前已有部分支付方採用了這種做法。我認為真正能改變現狀的驅動力，是我們獲得產品結果數據的時候。

Thank you, Bob. It's Len. Just to amplify on that. Seems to me there are three important factors you can consider.

謝謝你，鮑伯。是倫。補充一點。在我看來，有三個重要因素需要考慮。

Assuming that we have a relatively high satisfaction rate that patients who get on the drug, get their cholesterol lowered and tolerate the drug, this is not like the Hepatitis C market. Those should be long-term patients. So we begin to accumulate them, as opposed to constantly having to find to replace, as you would, let's say, in a Hep C environment.

假設患者的滿意度相對較高，即服用該藥物的患者膽固醇降低且耐受性良好，但這與丙型肝炎市場的情況不同。這些應該是長期住院病人。因此，我們可以開始累積它們，而不是像在C型肝炎環境中那樣，需要不斷地尋找替代品。

Secondly, as Bob said, the cardiologists are not like the rheumatologists, where they have people in their office who are very experienced in dealing with these prior authorizations and paperwork. And I think that they are getting more efficient at it. They are somewhat frustrated by it, for sure. And some of them are giving up.

其次，正如鮑伯所說，心臟科醫生不像風濕病專家那樣，他們的辦公室裡有經驗豐富的人員來處理這些事先授權和文書工作。我認為他們在這方面效率越來越高了。他們對此確實感到有些沮喪。他們中有些人正在放棄。

Some say, well, I'll wait for outcomes before I go to the mat with fights and things like that. But I do believe that the experience of the doctors in picking the patients that they know that each PBM for each patient, or each payer, if you will, they kind of know, are getting better at knowing how to get this done as they get more experience.

有人說，我會等結果出來後再去打架什麼的。但我相信，隨著醫生們經驗的積累，他們在挑選病人方面越來越熟練，因為他們知道每個病人的每個藥品福利管理機構（PBM）或每個付款方（如果你願意這麼說的話）的情況，他們也越來越擅長完成這項工作。

And then of course, finally, as George mentioned, we hope that the outcomes data later this year will change the dynamic out there in terms of the feeling, the compelling need to go on these products, if we show an outcomes benefit. Next question.

最後，正如喬治所提到的，我們希望今年稍後公佈的結果數據能夠改變目前市場上的動態，改變人們對這些產品的感受和迫切需求，前提是我們能夠證明這些產品具有療效。下一個問題。

Our following question comes from Ronny Gal from Bernstein.

接下來的問題來自伯恩斯坦公司的 Ronny Gal。

One second.

一秒鐘。

Do you have a question?

你有什麼問題嗎？

Yes, right here. Sorry. Actually, never mind.

對，就是這裡。對不起。其實，算了。

Okay. Next question.

好的。下一個問題。

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

接下來的問題來自美國銀行美林證券的黃穎。

Good morning. Thank you for taking my question. Just one more on PDGF. If you look at it for [Verstar] plus Lucentis, it seems to have, there's four-letter difference. Can you help us frame the fractation for your [call] formulated EYLEA plus PDGF antibody? I know you're comparing to EYLEA, of course. So does that four-letter apply in this case? And what are you expecting from the outcome? Thank you.

早安.感謝您回答我的問題。關於PDGF，再補充一點。如果你看一下 [Verstar] 和 Lucentis，你會發現它們之間似乎有四個字母的差別。您能否幫助我們確定您配製的 EYLEA 加 PDGF 抗體的分級分離方法？我知道你肯定是在拿它跟愛樂比較。那麼，這個四字母縮寫詞是否適用於此案？你對結果有何預期？謝謝。

We consider it very hard to interpret these sort of existing studies. Because as I said, we've actually seen, with larger studies, when you actually repeat the study, four-letter differences easily go away. So we really consider this a very early field and based on a lot of the science, it's really very, very hard to predict what, if any, benefit will be seen here.

我們認為很難解讀這類現有研究。因為正如我所說，我們已經透過更大規模的研究發現，當你重複這項研究時，四個字母的差異很容易消失。因此，我們認為這確實是一個非常早期的領域，根據許多科學研究來看，真的很難預測這裡將會看到什麼好處（如果有的話）。

We do think that our unique two-stage design will end up giving us probably the best data and most convincing perspective on whether there is an added benefit or not. And as Len pointed out, the fact that if there is an added benefit, we'll be able to do it with a single injection, and assuming appropriate safety, we'll make it easier to deliver that benefit to patients with this approach. And remember, our approach here, we're combining two very similar antibody-like drugs into a single co-formulated injection, as opposed to giving two very different types of drugs with separate injections.

我們認為，我們獨特的兩階段設計最終可能會為我們提供最佳的數據和最令人信服的觀點，以判斷是否有額外的好處。正如 Len 指出的那樣，如果能帶來額外的益處，我們只需注射一次就能實現，而且在安全性允許的情況下，這種方法能更方便地為患者帶來益處。請記住，我們採用的方法是將兩種非常相似的抗體樣藥物組合成一種聯合製劑注射劑，而不是分別注射兩種截然不同的藥物。

Great. Next question.

偉大的。下一個問題。

Our following question comes from Geoffrey Porges from Leerink.

接下來的問題來自 Leerink 的 Geoffrey Porges。

Thank you very much for taking the question. Just on dupilumab, George, could you comment, first, on the conjunctivitis? Is that signal real, and are you seeing it in the other studies, for example, in asthma or esophagitis? And then related to that, could you just talk a little about the launch outlook? What are the parallels or differences to the Praluent experience and how might you get payers to let some patients through in this case?

非常感謝您回答這個問題。喬治，關於度普利尤單抗，你能否先談談結膜炎的問題？這個訊號是真實的嗎？你在其他研究中也看過嗎，例如在氣喘或食道炎研究中？另外，您能否談談發布前景？與 Praluent 的經驗有哪些相似之處或不同之處？在這種情況下，如何才能讓支付方允許一些患者獲得治療？

Okay. Well, the first part, very interesting in terms of the conjunctivitis. We have consistently seen it in our atopic dermatitis studies. We have not seen it in our asthma.

好的。嗯，第一部分很有意思，因為它涉及了結膜炎。我們在異位性皮膚炎研究中一直觀察到這種情況。我們在哮喘病中並沒有發現這種情況。

As you know, there's differences, for examples, in the way topical steroids are used in the populations and so forth, and we have various ideas about why this may be the case. That said, even though it seems specific to the way the drug is being used in this particular patient population, and perhaps with either the use or actually the less use of topical steroids in the treated patients, the comforting thing is that these patients do have, as we pointed out in the call, they do have already a lot of history of conjunctivitis. So this is not really something brand-new to the patients.

如您所知，例如，不同人群使用外用類固醇的方式存在差異等等，我們對造成這種情況的原因有各種看法。也就是說，儘管這似乎與該藥物在該特定患者群體中的使用方式有關，或許與接受治療的患者使用或較少使用局部類固醇有關，但令人欣慰的是，正如我們在電話會議中指出的那樣，這些患者確實有很多結膜炎病史。所以這對患者來說並不是全新的情況。

And the conjunctivitis that is seen here on dupilumab seems to be of mild to moderate severity and is limited. Most cases actually resolve during treatment and very few, if any, cases actually lead to discontinuation. So it seems as if the benefit/risk is really maintained in the face of this.

使用度普利尤單抗引起的結膜炎似乎程度較輕至中度，且侷限於局部。大多數病例在治療過程中都能緩解，極少有病例會導致治療中斷。所以，在這種情況下，收益/風險比似乎仍然保持不變。

That said, also, in terms of the second part of your question about dupilumab, we think it's a very different situation compared to Praluent. There is a huge unmet need here. Patients are really suffering from ongoing symptomatology, and the data actually shows that this symptomatology is actually markedly improved with the dupilumab treatment.

也就是說，關於您提出的關於度普利尤單抗的第二部分問題，我們認為它與普拉魯恩的情況截然不同。這裡存在著巨大的未滿足需求。患者確實正在遭受持續症狀的折磨，而數據顯示，使用度普利尤單抗治療後，這些症狀實際上得到了顯著改善。

So that it seems to us that there's going to be a lot of patients who really are -- and we already know -- who are going to be so positively impacted in their life that they're going to be demanding this drug. And it seems to us that these patients will deserve to have this first systemic therapy that can really make a difference in their lives.

因此，我們認為會有很多患者——而且我們已經知道——他們的生活會因此受到如此積極的影響，以至於他們會要求使用這種藥物。我們認為，這些患者應該得到這種能夠真正改變他們生活的首個系統性治療。

Let me remind you that we're talking about the most moderate to severe class of the patients here, which are more than 1 million patients in the United States alone. And these patients really have very few other alternatives. And as you see with our data in CHRONOS, where we treat on top of topical steroids, the standard of care, very few, only about 10% of the patients or so, become clear or almost clear with topical steroids, as opposed to about 40% on the drug.

我要提醒各位，我們這裡討論的是病情最嚴重的患者群體，光在美國就有超過 100 萬患者。而且這些患者實際上幾乎沒有其他選擇。正如您在 CHRONOS 的數據中看到的那樣，我們在局部類固醇（標準療法）的基礎上進行治療，只有大約 10% 的患者通過局部類固醇治療後病情得到緩解或幾乎緩解，而單獨使用藥物治療的患者中約有 40% 的人病情得到緩解。

And there's not only, of course, the cosmetic effects of having these skin lesions and so forth, and the associated infections and so forth that you get, but there's an enormous amount of itch, which drives a lot of behavioral problems and so forth. There's associated depressive and psychological symptomatology here and so forth, and we've actually shown that much of this is actually impacted in our studies.

當然，除了這些皮膚損傷帶來的外觀影響等等，以及相關的感染等等之外，還會產生巨大的搔癢感，從而引發許多行為問題等等。這裡有相關的憂鬱和心理症狀等等，而我們的研究實際上已經表明，其中許多方面都受到了影響。

So we think this can be a very important drug for this population of patients. And we think that there's going to be a very important opportunity to make a lot of difference in a lot of peoples' lives, which is what should count in this business.

所以我們認為這對這部分患者來說可能是一種非常重要的藥物。我們認為，這將是一個非常重要的機會，可以對許多人的生活產生很大的影響，而這才是這個行業真正應該關注的。

But beyond that, I think we also have to remember that dupilumab is really a franchise onto itself. The data really suggests that we have hit upon here, with blocking both interleukin 4 and 13, the critical drivers of allergic disease in general.

但除此之外，我認為我們還要記住，dupilumab 本身就是一個獨立的產品線。數據確實表明我們已經找到了解決方案，即阻斷白細胞介素 4 和 13，這兩種物質是過敏性疾病的關鍵驅動因素。

We're hoping ODYSSEY to extend the findings from our first pivotal study in asthma by confirming them with the second pivotal study. And we will also be continuing to study in other allergic diseases where, as you've already seen, we already have some positive data in other allergic diseases in early stage studies, as well. So this can benefit not only the allergic and ectopic diseases of atopic dermatitis, but we hope to be able to have studies that confirm it for additional allergic diseases, as well.

我們希望 ODYSSEY 能夠透過第二次關鍵性研究來證實我們第一次關鍵性氣喘研究的發現，從而擴展這些發現。我們將繼續研究其他過敏性疾病，正如您所看到的，我們在早期研究中也已在其他過敏性疾病方面獲得了一些積極的數據。因此，這不僅可以對過敏性和異位性異位性皮膚炎有益，而且我們希望有研究證實它對其他過敏性疾病也有效。

I just wanted to add one thing, Geoff. In terms about the difference between Praluent, just to re-emphasize what George already said, which is that most people don't like to think of themselves as sick and they don't like to have to take a cholesterol lowering drug, oh, I'll fix it with diet or I'll take my statin or what have you. But patients with atopic dermatitis really suffer. It's really made its way into pop culture.

傑夫，我只想補充一點。關於 Praluent 與其他藥物的區別，我只想再次強調喬治已經說過的話，那就是大多數人都不喜歡認為自己生病了，也不喜歡服用降膽固醇藥物，他們會想：哦，我可以通過飲食來解決這個問題，或者我服用他汀類藥物等等。但患有異位性皮膚炎的患者確實飽受折磨。它已經真正融入了流行文化。

There's a new series on HBO, I don't know if any of you have seen it, called "The Night Of". And the actor, John Turturro, portrays this lawyer who suffers terribly from atopic dermatitis. He has to wear sandals. He goes to group to discuss all this. And it really has a terrible impact on his life. And I don't think this is just a TV portrayal. I think this is what we see, that people really suffer from this disease.

HBO推出了一部新劇，不知道你們有沒有看過，叫做《罪夜之奔》。演員約翰特托羅飾演這位患有嚴重異位性皮膚炎的律師。他必須穿涼鞋。他去參加小組討論這些事情。這件事對他的生活造成了非常糟糕的影響。我認為這不僅僅是電視節目的詮釋。我認為這就是我們所看到的，人們確實深受這種疾病的折磨。

I think one last point to just add, as well, is that unlike most other biologics that are immunomodulators, where you see in general, whether it's the TNFs or a variety of other classes, your generally see a doubling of the serious infection risk rate. This appears to be more of an immunomodulator that is correcting an immune deviation. And actually, as we reported and as we summarized during this call, there is no increase in infections and in serious infections here.

最後我想補充一點，與其他大多數生物製劑（免疫調節劑）不同，無論是 TNF 還是其他各種類別的免疫調節劑，通常都會使嚴重感染風險率翻倍。這似乎更像是一種免疫調節劑，可以糾正免疫偏差。事實上，正如我們報告和在這次電話會議上總結的那樣，這裡並沒有出現感染病例增加或重症感染病例增加的情況。

So once again, this is an important option that's being offered to the patients in contrast to other alternatives which were essentially immunosuppressing. And to have this sort of efficacy with a non-immunosuppressing agent, I think is also offering a lot of hope to patients.

因此，這再次為患者提供了一個重要的選擇，與其他本質上具有免疫抑製作用的替代方案相比，這種選擇更具優勢。而這種療效並非來自免疫抑制劑，我認為這也為患者帶來了極大的希望。

Okay. Next question.

好的。下一個問題。

Next question comes from Chris Raymond from Raymond James.

下一個問題來自Raymond James公司的Chris Raymond。

Hello. Thank you. So just another question here on dupilumab, in atopic dermatitis. Maybe for Bob, if possible. I'd imagine your marketing prep's pretty underway now, with the BLA submitted. And I know we know the vast majority of intervention here is topical corticosteroids.

你好。謝謝。所以，關於度普利尤單抗治療異位性皮膚炎，我還有一個問題。如果可能的話，或許對鮑伯來說是這樣。我想你們的行銷準備工作現在應該進展順利了，BLA申請也已經提交了。我知道，我們都知道，這裡絕大多數的介入措施都是局部使用皮質類固醇。

But just curious, what has your work uncovered in terms of the use of other biologics off label in physician satisfaction with these agents? And maybe can you talk about how you're thinking about this as you formulate your launch plans? Thank you.

我很好奇，您的研究在其他生物製劑的超適應症使用方面，以及醫生對這些藥物的滿意度方面，有哪些發現？或許您能談談在製定發布計劃時，您是如何考慮這個問題的嗎？謝謝。

Sure. So as George pointed out, there are approximately 1.6 million patients in the United States who are uncontrolled on topical therapies who have moderate to severe atopic dermatitis. A very small proportion of those patients have received other therapies, immunosuppressant agents, generally not biologics, but things like cyclosporine and methotrexate.

當然。正如喬治指出的那樣，美國大約有 160 萬中度至重度異位性皮膚炎患者，他們的病情無法透過局部治療得到控制。極少數患者接受了其他療法，即免疫抑制劑，通常不是生物製劑，而是環孢素和甲氨蝶呤之類的藥物。

The challenge with those therapies is you can't use them long term. They've got some toxicities that really interfere with the patient's long-term use of the therapy and, thus, their symptoms will come back, their itch will come back, and their quality of life will decrease.

這些療法的缺點在於不能長期使用。這些藥物有一些毒性，會嚴重干擾患者長期使用該療法，因此，他們的症狀會復發，搔癢會復發，生活品質會下降。

So there is a huge opportunity for dupilumab in these uncontrolled moderate to severe patients. There's a pent-up demand among patients and physicians to get the patients on therapy and to improve their lives.

因此，度普利尤單抗對於這些病情控制不佳的中度至重度患者來說，具有巨大的應用前景。患者和醫生都迫切希望患者能夠接受治療，改善他們的生活。

And to add to that, in terms of biologics, we do not believe that there's any convincing evidence with any available approved biologics that show efficacy in this disease setting. And as you know, there's also no other late stage biologics that are promising in this area. So this really has a chance to really be providing something to patients that don't really have any other alternatives, at this point.

此外，就生物製劑而言，我們認為目前沒有任何已批准的生物製劑能夠令人信服地證明其對這種疾病有效。而且，如您所知，目前該領域也沒有其他處於後期研發階段且前景良好的生物製劑。所以，這確實有機會為目前沒有其他選擇的患者提供一些幫助。

I would add also that to make sure you think about these other diseases as other significant opportunities. There's been a desire to have a drug, like a biologic, that could affect, in asthma, for example, that could treat all patients, that could have an effect both on FEV-1 and on exacerbations, and no such drug has been forthcoming, as yet. And we're excited that our first pivotal trial demonstrated in the broad population effect both on FEV-1 and on exacerbation.

我還要補充一點，一定要把這些其他疾病也當成其他重要的機會。人們一直渴望擁有一種像生物製劑一樣的藥物，例如，可以治療氣喘，治療所有患者，既能影響 FEV-1，又能減少病情加重，但目前還沒有這樣的藥物問世。我們很高興，我們的第一個關鍵性試驗在廣泛的人群中證明了對 FEV-1 和病情加重的影響。

So hopefully, if we can confirm that in our trial that's just about to be completed in enrollment, so think ahead about a year for the trial and then the data, we could be onto something, a whole new opportunity which people really are looking for, something that can treat all the patients, and that can treat both the FEV-1 and the exacerbations.

所以，如果我們能在即將完成招募的試驗中證實這一點（預計試驗將持續一年左右，屆時我們將獲得數據），我們或許就能找到一些新的東西，一個人們真正渴望的全新機會，一種可以治療所有患者，並且可以治療 FEV-1 和病情加重的療法。

As Len briefly touched upon, a very important feature that, of course, we're hoping to confirm in our second pivotal study is this point about the broad population. So far, biologics have been limited to the so-called, the more allergic or eosinophilic-type patients, and is the only places where substantial efficacy has been noted. And it's, as Len said, mostly only with exacerbations and not on lung function. If we can confirm results of the first pivotal, it could provide another major hope for patients who really need these types of therapies.

正如 Len 簡要提到的，一個非常重要的特徵，當然，我們希望在第二次關鍵研究中證實這一點，是關於廣大人群的。到目前為止，生物製劑僅限於所謂的過敏性或嗜酸性粒細胞型患者，也是唯一在這些患者中觀察到顯著療效的領域。正如 Len 所說，這主要只與病情加重有關，與肺功能無關。如果我們能夠確認第一個關鍵性試驗的結果，那麼對於真正需要這類療法的患者來說，這將帶來另一個重大希望。

And the last point on that, which I know George likes to make when he speaks about this at meetings, is that we can't forget the fact that people who have asthma frequently have atopic dermatitis and people who have atopic dermatitis frequently have asthma. These are overlapping syndromes, because they are scientifically related, I should say pathophysiologically related, we think through the IL-4-13 pathway.

最後一點，我知道喬治在會議上談到這個問題時喜歡強調，那就是我們不能忘記，患有氣喘的人常常患有異位性皮膚炎，而患有異位性皮膚炎的人也常常患有氣喘。這些是重疊的綜合徵，因為它們在科學上相關，應該說在病理生理學上相關，我們認為它們都與 IL-4-13 路徑有關。

Next question.

下一個問題。

Next question comes from Mark Schoenbaum from Evercore IS.

下一個問題來自 Evercore IS 的 Mark Schoenbaum。

Good morning. It's John Scotti in for Mark. Maybe I'll ask a quick one on the Adicet collaboration. Could you just elaborate a little bit more on the technology behind the off-the-shelf therapies there and how does that approach differ from those that are already in development, such as selectis, and maybe when could we see some of those assets entering the clinic?

早安.約翰·斯科蒂將代替馬克上場。或許我可以快速問一下關於 Adicet 合作的問題。您能否再詳細介紹一下這些現成療法背後的技術，以及這種方法與目前正在開發的療法（例如 Selectis）有何不同？我們什麼時候才能看到其中一些療法進入臨床試驗階段？

Wait, before you answer that, George. I just wanted to make one comment, that is if I went to Broadway and had so many stand-in actors, I would be mortified. Go ahead. (Laughter)

喬治，等你回答這個問題之前，先等等。我只想說一句，如果我去百老匯演出，發現有這麼多替身演員，我會感到非常尷尬。前進。（笑聲）

I think an important point to make is we really believe in people and we believe in synergies. And we've had long-standing interests to be working with Aya Jacobovits, who's really leading Adicet. And obviously, she's been in areas that we've been in. We have enormous respect for her, her capabilities. And so we really feel that we can work well together with her and her team.

我認為需要強調的一點是，我們真心相信人，也相信綜效。我們一直很想與 Aya Jacobovits 合作，她實際上是 Adicet 的領導者。顯然，她去過我們去過的地方。我們非常尊敬她，也很敬佩她的能力。因此，我們真心覺得我們能夠與她和她的團隊合作愉快。

And number two is the synergies with our existing programs, this is why we make these sorts of deals. We believe that we have a lot of potential tools and starting points for making the sorts of targeting reagents that would be introduced into these cell therapies using our existing technologies, such as our VelocImmune and our Veloci-Next technologies, which really nobody else in this field has access to right now.

第二點是與我們現有專案的協同效應，這就是我們達成這類交易的原因。我們相信，我們擁有許多潛在的工具和起點，可以利用我們現有的技術（例如我們的 VelocImmune 和 Veloci-Next 技術）來製造將要引入這些細胞療法的靶向試劑，而目前該領域的其他人實際上都無法獲得這些技術。

So we're hoping that we put together our unique capabilities that nobody else in the cell therapy space had a leader in this area, such as Aya Jacobovits and her team, that we could really do special things. And I think at this point, that's what we want to say about this collaboration.

所以我們希望，憑藉我們獨特的優勢，像 Aya Jacobovits 和她的團隊這樣在細胞治療領域無人能及的領導者，我們能夠真正做出一些特別的事情。我想，在這一點上，這就是我們想對這次合作說的話。

Next question.

下一個問題。

Our next question comes from RBC Capital.

下一個問題來自加拿大皇家銀行資本市場。

Thank you, folks. Let me ask a 10-Q question. It lists PD-1 as embarking on potentially pivotal studies over the next year. Are there unique indications or combinations that you've selected already? Any details there, please.

謝謝大家。讓我問一個包含10個問題的問題。報告指出，PD-1 將在未來一年內進行一些可能具有關鍵意義的研究。您是否已經選擇了獨特的適應症或組合？請問還有什麼細節嗎？

Yes. So it's already been publicly disclosed that we're already in a potentially registration study in a unique indication that we think has a lot of promise for various reasons and where we've already seen early clinical activity in our earlier studies, which is cutaneous squamous cell carcinoma. And so that is, for example, one setting. We've also identified additional settings -- that has been publicly disclosed -- we've also identified additional settings that we'll be going into, we hope both potentially with it as a monotherapy, but also with new combinations.

是的。我們已經公開披露，我們正在進行一項針對特定適應症的潛在註冊研究，我們認為該適應症由於各種原因很有前景，而且我們在早期的研究中已經看到了早期的臨床活性，該適應症是皮膚鱗狀細胞癌。例如，這是一個設定。我們也確定了其他一些應用場景——這一點已經公開披露——我們希望這些應用場景既可以作為單一療法，也可以與其他療法結合使用。

Great. And we have time for one last question.

偉大的。我們還有時間回答最後一個問題。

Our final question comes from Alethia Young from Credit Suisse.

最後一個問題來自瑞士信貸的阿萊西亞·楊。

Thank you for squeezing me in here. Going back to your prepared remarks, I was wondering with EYLEA, is it something that you're starting to experience as -- what are the dynamics for why the financial incentives that manufacturers were providing are increasing, or group purchasing? Why did you specifically bring that to our attention this quarter? Thank you.

謝謝你擠出時間讓我進來。回到您準備好的發言，我想問一下，就安樂死而言，您是否開始感受到製造商提供的經濟激勵措施或團購活動正在增加？背後的驅動因素是什麼？為什麼您特意在本季提出這個問題？謝謝。

I think that Bob is highlighting to you what's going on in the marketplace. And we're seeing more of these things than we have in years past. It's not been any drastic change. But it's just to get in front of these things. We monitor them and we have responses prepared, should they be necessary.

我認為鮑伯是在向你強調市場上正在發生的事情。而且，我們看到的這類事情比往年多得多。並沒有發生任何劇烈的變化。但這樣做只是為了提前應對這些事情。我們會密切關注事態發展，並已做好應對準備，以備不時之需。

Bob, want to add anything there?

鮑勃，你還有什麼要補充的嗎？

It's a dynamic in the marketplace that impacts the growth of EYLEA, and we just wanted to discuss it.

這是影響安永成長的市場動態，我們想就此進行探討。

Okay. Great. Well, that concludes today's call. I want to thank everyone for joining. As we said, myself, Bob Landry and the IR team will be available for follow-up questions, if you have any. Please e-mail us or give us a call. Operator?

好的。偉大的。好了，今天的電話會議到此結束。感謝大家的參與。正如我們所說，如果您有任何後續問題，我和鮑勃·蘭德里以及投資者關係團隊將隨時為您解答。請給我們發郵件或打電話。操作員？

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

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