雷傑納榮製藥 (REGN) 2019 Q2 法說會逐字稿

Welcome to the Regeneron Pharmaceuticals Q2 2019 Earnings Conference Call. My name is John, and I'll be your operator for today's call. (Operator Instructions) Please note, the conference is being recorded.

歡迎參加 Regeneron Pharmaceuticals 2019 年第二季財報電話會議。我叫約翰，我將擔任您今天通話的接線生。（操作員說明）請注意，會議正在錄音。

And I will now turn the call over to Justin Holko.

現在我將把電話交給賈斯汀·霍爾科。

Thank you, John. Good morning, good afternoon and good evening to everyone listening around the world. Thank you for your interest in Regeneron Pharmaceuticals, and welcome to the second quarter 2019 conference call. An archive of this webcast will be available on our website.

謝謝你，約翰。全世界的聽眾朋友們，早安、下午好、晚上好！感謝您對 Regeneron Pharmaceuticals 的關注，歡迎參加 2019 年第二季電話會議。本次網路直播的錄影檔案將會發佈在我們的網站上。

Joining me today are Dr. Leonard Schleifer, Founder, President and Chief Executive Officer; Dr. George Yancopoulos, Founding Scientist, President and Chief Scientific Officer; Marion McCourt, Senior Vice President and Head of Commercial; and Bob Landry, Executive Vice President and Chief Financial Officer. After our prepared remarks, we will open the call for Q&A.

今天與我一同出席的有：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；高級副總裁兼商務主管 Marion McCourt；以及執行副總裁兼財務長 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 our remarks made on the 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, financial forecasts and guidance, development programs and related anticipated milestones, collaborations, finances, regulatory matters, payer coverage and reimbursement issues, intellectual property and pending litigation and competition. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-Q for the quarterly period ended June 30, 2019, which has been filed with the SEC today.

我還要提醒各位，我們今天在電話會議上發表的言論包括有關 Regeneron 的前瞻性聲明。此類聲明可能包括但不限於與 Regeneron 及其產品和業務、財務預測和指導、開發計劃和相關預期里程碑、合作、財務、監管事項、支付方覆蓋範圍和報銷問題、智慧財產權以及未決訴訟和競爭相關的聲明。每項前瞻性聲明都存在風險和不確定性，可能導致實際結果和事件與該聲明中預測的結果和事件有重大差異。有關這些及其他重大風險的更完整描述，請參閱 Regeneron 向美國證券交易委員會提交的文件，包括其截至 2019 年 6 月 30 日的季度報告（10-Q 表格），該表格已於今日提交給美國證券交易委員會。

Regeneron does not undertake any obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise.

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 those measures to GAAP is available in our financial results press release, which can be accessed on our website.

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上查閱。

Once our call concludes, Bob Landry and the IR team will be available to answer further questions.

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, Justin. Before we begin, I'd like to extend a warm welcome to Justin, who joined us early this summer after completing a 19-year training program at Merck and has immediately hit the ground running here at Regeneron. We're thrilled to have him as part of the team, and we worked hard to make his first quarter a straightforward one. Thanks to everyone for joining the call.

謝謝你，賈斯汀。在正式開始之前，我想熱烈歡迎賈斯汀加入我們。他於今年夏天早些時候在默克公司完成了 19 年的培訓計劃，並立即在再生元公司投入了工作。我們很高興他能加入團隊，我們也努力讓他的第一個季度過得順利。感謝各位參與通話。

And turning to our business. We had a great quarter actually marked by top and bottom line growth as well as important advances across our innovative R&D engine. Sales at Regeneron products, including those recorded by our partners, grew 32% compared to the second quarter of 2018.

接下來談談我們的業務。本季我們取得了巨大的成功，營收和利潤均實現成長，而且我們在創新研發方面也取得了重要進展。包括我們的合作夥伴記錄的銷售額在內，Regeneron 產品的銷售額與 2018 年第二季度相比增長了 32%。

EYLEA global net sales grew 13% to $1.9 billion, including U.S. EYLEA net sales growth of 17% to $1.16 billion. The diabetic retinopathy approval in May continues to build upon EYLEA's leadership position in treating retinal diseases, including wet age-related macular degeneration, diabetic macular edema and retinal vein occlusion.

EYLEA 全球淨銷售額成長 13% 至 19 億美元，其中美國 EYLEA 淨銷售額成長 17% 至 11.6 億美元。5 月糖尿病視網膜病變的批准進一步鞏固了 EYLEA 在治療視網膜疾病（包括濕性老年黃斑部病變、糖尿病性黃斑水腫和視網膜靜脈阻塞）方面的領先地位。

We are also pleased to announce that our antibody collaboration with Sanofi achieved profitability this quarter. We expect profits to continue to increase driven by growth in DUPIXENT as well as disciplined cost management across the collaboration to stem losses from PRALUENT by better aligning investments with revenues.

我們也很高興地宣布，我們與賽諾菲的抗體合作計畫在本季度實現了盈利。我們預計，在 DUPIXENT 成長的推動下，利潤將繼續成長，同時透過更好地將投資與收入相匹配，加強合作，從而遏制 PRALUENT 的虧損，並實施嚴格的成本管理。

DUPIXENT is fulfilling its potential to improve the lives of patients by transforming the treatment of a variety of Type 2 allergic diseases. Global net sales are now annualizing at more than $2 billion. Patient initiations in the U.S. are growing, and many ex U.S. launches are just beginning.

DUPIXENT 正在發揮其潛力，透過改變多種 2 型過敏性疾病的治療方式來改善患者的生活。全球淨銷售額目前年化超過20億美元。美國的患者啟動治療數量正在成長，而許多美國以外的地區也剛開始推出相關產品。

Building on this commercial momentum, in June, we received FDA approval for DUPIXENT in chronic rhinosinusitis with nasal polyposis. In the EU, DUPIXENT was approved in May for severe asthma in adults and adolescents, and as we announced this morning, was just approved for atopic dermatitis in the adolescent patients.

憑藉這一商業勢頭，我們在 6 月獲得了 FDA 對 DUPIXENT 用於治療慢性鼻竇炎伴鼻息肉的批准。在歐盟，DUPIXENT 於 5 月獲批用於治療成人和青少年的嚴重氣喘，正如我們今天早上宣布的那樣，它剛剛獲批用於治療青少年患者的異位性皮膚炎。

We also announced today the strong positive results of our Phase III study in children aged 6 to 11 with severe atopic dermatitis. We are enthusiastic about the current and future prospects for DUPIXENT as a treatment directed at the underlying cause of allergic diseases.

今天我們也宣布了針對 6 至 11 歲患有嚴重異位性皮膚炎的兒童的 III 期研究的積極結果。我們對 DUPIXENT 作為一種針對過敏性疾病根本原因的治療方法的當前和未來前景感到興奮。

Additionally, we are making significant progress towards our goal of building a leading presence in immuno-oncology. The U.S. and EU approvals for Libtayo in advanced cutaneous squamous cell carcinoma are just the beginning. Our clinical efforts, which now include multiple different immuno-oncology programs are studying a wide variety of potential drug candidates in several difficult-to-treat cancers, including non-small cell lung cancer, basal cell carcinoma, cervical cancer, ovarian cancer, non-Hodgkin's lymphoma, multiple myeloma and prostate cancer.

此外，我們在建立免疫腫瘤學領域領先地位的目標上取得了重大進展。Libtayo 獲得美國和歐盟批准用於治療晚期皮膚鱗狀細胞癌，但這只是個開始。我們目前的臨床研究工作包括多個不同的免疫腫瘤學項目，正在研究多種潛在候選藥物，用於治療多種難以治療的癌症，包括非小細胞肺癌、基底細胞癌、子宮頸癌、卵巢癌、非何杰金氏淋巴瘤、多發性骨髓瘤和前列腺癌。

Beyond oncology, we continue to move novel programs forward throughout early and late-stage development. George will speak to a few of these programs, and additional data readouts are expected later this year.

除了腫瘤學領域，我們也在早期和後期研發階段持續推動創新項目。喬治將與其中一些項目進行交流，預計今年稍後將公佈更多數據。

We've made critical advances that have led both to top line and bottom line growth, but we recognize that these advances may be overshadowed by the current policy debates on the affordability and accessibility of innovative medicines. We continue to work with policymakers to develop responsible solutions that address affordability and accessibility while preserving incentives to develop transformative treatments of the future.

我們取得了關鍵性的進展，實現了營收和利潤的成長，但我們也意​​識到，這些進展可能會被當前關於創新藥物的可負擔性和可及性的政策辯論所掩蓋。我們將繼續與政策制定者合作，制定負責任的解決方案，在解決負擔能力和可及性問題的同時，維持開發未來變革性療法的激勵措施。

Now I'll turn the call over to George.

現在我把電話交給喬治。

Thanks, Len. Let me begin with EYLEA, the market leader based on its ability to improve vision across multiple retinal diseases along with its safety profile established by over 25 million injections. In addition to EYLEA's indication for the treatment of wet AMD or macular edema following retinal vein occlusion and for diabetic macular edema, or DME, the FDA label for EYLEA was expanded in May to include diabetic retinopathy without centrally involved DME based on the PANORAMA study.

謝謝你，Len。首先，我想介紹一下愛立信（EYLEA），它是市場領導者，因為它能夠改善多種視網膜疾病患者的視力，並且經過超過 2500 萬次注射驗證，安全性極高。除了 EYLEA 原有的用於治療濕性 AMD 或視網膜靜脈阻塞後黃斑水腫以及糖尿病性黃斑水腫 (DME) 的適應症外，根據 PANORAMA 研究，FDA 於 5 月擴大了 EYLEA 的適應症範圍，將不涉及中心性 DME 的糖尿病視網膜病變也納入其中。

In this diabetic retinopathy setting, our updated label shows that EYLEA demonstrated an 85% to 100% reduction in the incidence of vision-threatening complications. In addition, we are awaiting FDA action on our resubmitted filing for the EYLEA prefilled syringe.

在糖尿病視網膜病變的情況下，我們更新的標籤顯示，EYLEA 使威脅視力的併發症發生率降低了 85% 至 100%。此外，我們也正在等待 FDA 對我們重新提交的 EYLEA 預充填式註射器申請的處理結果。

In terms of our future innovation in retinal disease, we are planning to initiate clinical programs with a higher dose formulation of aflibercept in wet AMD and in DME by the end of 2019. These studies will test a higher dose of aflibercept in 12- and 16-week regimens compared to the recommended EYLEA regimen of 2 milligrams every 8 weeks.

就我們未來在視網膜疾病方面的創新而言，我們計劃在 2019 年底前啟動針對濕性 AMD 和 DME 的更高劑量阿柏西普製劑的臨床計畫。這些研究將測試 12 週和 16 週療程中更高劑量的阿柏西普，與建議的 EYLEA 方案（每 8 週 2 毫克）相比。

Beyond aflibercept, we are continuing preclinical development of a new VEGF blocker, gene therapy and other novel approaches, including with our new collaborators at Alnylam.

除了阿柏西普之外，我們還在繼續進行新的 VEGF 阻斷劑、基因療法和其他新方法的臨床前開發，包括與我們在 Alnylam 的新合作夥伴一起進行開發。

I'd like to now turn to DUPIXENT, our breakthrough therapy that is already benefiting many patients in a wide variety of atopic and/or allergic diseases. As Len mentioned, we achieved several important regulatory milestones. Beyond the highlighted approvals, an opinion by the European Committee for Medicinal Products for Human Use, or CHMP, for chronic rhinosinusitis with nasal polyposis is anticipated by the end of 2019.

現在我想談談DUPIXENT，這是我們的突破性療法，它已經使許多患有各種特異性疾病和/或過敏性疾病的患者受益。正如 Len 所提到的，我們實現了幾個重要的監管里程碑。除了上述重點批准外，預計歐洲人用藥品委員會（CHMP）將於 2019 年底就慢性鼻竇炎伴鼻息肉的治療發表意見。

And just this morning, we announced positive results of the Phase III trial in severe pediatric atopic dermatitis patients aged 6 to 11 years, which we intend to submit to regulators in the coming months.

就在今天早上，我們宣布了針對 6 至 11 歲重度兒童異位性皮膚炎患者的 III 期試驗的積極結果，我們計劃在未來幾個月內將結果提交給監管機構。

I would like to remind you of the tremendous unmet need in this population. On average, the children in our study had nearly 60% of their body covered with lesions and had suffered from this disease for most of their lives, leaving the children and their families devastated and without much hope. Not only did DUPIXENT dramatically reduce skin involvement as measured by EASI score by an average of about 80% but it also improved measures of anxiety, depression and health-related quality of life for both the children and their families.

我想提醒各位，這個群體中存在著巨大的未滿足需求。在我們的研究中，平均而言，兒童身上近 60% 的皮膚都覆蓋著病變，並且一生中大部分時間都飽受這種疾病的折磨，這讓兒童及其家人感到絕望和無助。DUPIXENT 不僅使 EASI 評分平均降低了約 80% 的皮膚受累情況，而且還改善了兒童及其家庭的焦慮、憂鬱和健康相關的生活品質。

The study also confirmed DUPIXENT's established safety profile, and once again, numerically reduced skin infections. We are deeply committed to bringing DUPIXENT to patients suffering from a range of Type 2 inflammatory diseases driven by the interleukin-4 and interleukin-13 pathways. With that goal in mind, we are actively enrolling patients in Phase III studies in eosinophilic esophagitis and chronic obstructive pulmonary disease, or COPD.

該研究還證實了 DUPIXENT 已確立的安全特性，並且再次在數量上減少了皮膚感染。我們致力於將 DUPIXENT 帶給患有由白細胞介素-4 和白細胞介素-13 通路驅動的各種 2 型發炎性疾病的患者。為了實現這一目標，我們正在積極招募患者參與嗜酸性食道炎和慢性阻塞性肺病（COPD）的 III 期研究。

As a reminder, we are also exploring the effectiveness of DUPIXENT in allergy desensitization settings such as for grass and peanut allergy. While allergy immunotherapy can be effective in the long term, many patients can't complete the prolonged time course required for success because of allergic reactions, which can be severe.

再次提醒大家，我們也在探索 DUPIXENT 在過敏減敏治療中的有效性，例如用於治療草和花生過敏。雖然過敏免疫療法從長遠來看可能有效，但許多患者因過敏反應而可能很嚴重，無法完成成功所需的長期療程。

We recently completed a small Phase IIa trial with about 25 patients per treatment arm, testing whether DUPIXENT could improve the safety, tolerability and efficacy of subcutaneous immunotherapy, or SCIT therapy, for grass allergy. The preliminary results of this study showed that about 30 (sic) [30%] patients discontinued therapy in the SCIT group mostly due to clinically meaningful allergic reactions compared to only a single patient who discontinued SCIT when combined with DUPIXENT and not due to an allergic reaction.

我們最近完成了一項小型 IIa 期試驗，每個治療組約有 25 名患者，測試 DUPIXENT 是否可以提高皮下免疫療法（SCIT 療法）治療草過敏的安全性、耐受性和療效。研究的初步結果顯示，SCIT 組中約有 30% 的患者因臨床上有意義的過敏反應而停止治療，而與 DUPIXENT 聯合治療時，只有一名患者停止了 SCIT 治療，且並非由於過敏反應。

And in the primary efficacy analysis, there was no difference in terms of reduction of the allergic symptoms with SCIT or in the combination. Thus, we are encouraged by the potential of DUPIXENT to increase the tolerability of SCIT therapy, and we're looking forward to presenting the results at a future medical meeting.

在主要療效分析中，SCIT 和合併治療在減輕過敏症狀方面沒有差異。因此，我們對 DUPIXENT 提高 SCIT 療法耐受性的潛力感到鼓舞，並期待在未來的醫學會議上展示研究結果。

Earlier this quarter, we reported that Regeneron 3500, our interleukin-33 antibody, met primary and secondary endpoints in a proof-of-concept study in moderate-to-severe asthma patients showing that Regeneron 3500 may provide an alternative therapeutic option for asthma, although the Regeneron 3500 results were numerically lower than those for the DUPIXENT calibrator arm.

本季度早些時候，我們報告稱，我們的白細胞介素-33 抗體 Regeneron 3500 在一項針對中重度氣喘患者的概念驗證研究中達到了主要和次要終點，表明 Regeneron 3500 可能為氣喘提供一種替代治療選擇，儘管 Regeneron 3500 的結果在數值上低於 DUPIXENT 校準組的結果。

In addition, the combination of Regeneron 3500 and DUPIXENT did not demonstrate increased benefit compared to DUPIXENT monotherapy in this trial, although the study was not powered for this comparison. In addition, within next 12 months, we're expecting interim results from the Phase II Regeneron 3500 studies in COPD and in atopic dermatitis.

此外，儘管該研究並非針對此比較而進行的，但在本試驗中，Regeneron 3500 和 DUPIXENT 的聯合治療並未顯示出比 DUPIXENT 單藥治療更高的療效。此外，在接下來的 12 個月內，我們預計將獲得 Regeneron 3500 在 COPD 和異位性皮膚炎方面的 II 期研究的中期結果。

I will now shift gears to our immunotherapy efforts to treat cancer. Starting with Libtayo. Last month, our PD-1 antibody was approved in the EU for adults with metastatic or locally advanced cutaneous squamous cell carcinoma who were not candidates for curative surgery or curative radiation, making Libtayo the first and only approved medicine of any kind for patients with advanced CSCC in the U.S. and Europe.

接下來，我將重點放在我們利用免疫療法治療癌症的工作。從Libtayo開始。上個月，我們的 PD-1 抗體在歐盟獲準用於治療不適合接受根治性手術或根治性放射治療的轉移性或局部晚期皮膚鱗狀細胞癌成年患者，這使得 Libtayo 成為美國和歐洲首個也是唯一一個獲批用於治療晚期皮膚鱗狀細胞癌患者的藥物。

With the goal of making Libtayo available for a broader population of CSCC patients, we started Phase III study in adjuvant CSCC. In addition to an ongoing investigator-initiated study, our study in the neoadjuvant setting is scheduled to start in the fourth quarter. Additionally, our pivotal study of Libtayo in basal cell carcinoma, the most common skin cancer, is expected to read out in the first half of next year.

為了讓更多 CSCC 患者能夠使用 Libtayo，我們啟動了 CSCC 輔助治療的 III 期研究。除了正在進行的研究者發起的研究外，我們在新輔助治療方面的研究計劃於第四季度開始。此外，我們對 Libtayo 治療基底細胞癌（最常見的皮膚癌）的關鍵性研究預計將於明年上半年公佈結果。

Moving on to non-small cell lung cancer. We are pleased by the enrollment for our Libtayo monotherapy Phase III trial in high PD-L1 expressors. We have commenced enrollment in part 2 of our other Phase III lung cancer study, which will compare Libtayo plus chemotherapy to chemotherapy alone regardless of PD-L1 status or histology.

接下來討論非小細胞肺癌。我們對 Libtayo 單藥治療 III 期試驗在 PD-L1 高表現患者的入組情況感到滿意。我們已開始招募另一項 III 期肺癌研究的第二部分患者，該研究將比較 Libtayo 加化療與單獨化療的療效，而不考慮 PD-L1 狀態或組織學。

Beyond checkpoint inhibition, our investigational bispecific antibody franchise consists of 2 broad categories based on the T cell receptor to which the bispecifics bind. The CD3 molecule or the CD28 costimulatory bispecifics. In total, we now have 4 bispecifics under clinical investigation.

除了檢查點抑制之外，我們正在研究的雙特異性抗體產品線根據雙特異性抗體結合的 T 細胞受體分為 2 大類。CD3 分子或 CD28 共刺激雙特異性抗體。目前，我們共有 4 種雙特異性抗體正在進行臨床研究。

Our CD20xCD3, BCMAxCD3, MUC16xCD3, and notably, the newest addition of our first costimulatory bispecific, PSMAxCD28. Additional candidates are expected to enter the clinic in the upcoming months and years.

我們的 CD20xCD3、BCMAxCD3、MUC16xCD3，以及值得一提的是，我們最新推出的第一個共刺激雙特異性抗體 PSMAxCD28。預計未來幾個月和幾年內，會有更多候選人進入診所。

In June, we presented updated efficacy and safety data for Regeneron 1979, our CD20xCD3 bispecific. Regeneron 1979 continues to show high response rates in heavily pretreated non-Hodgkin lymphoma patients. In particular, we observed complete responses in 4 out of 7 diffuse large B-cell lymphoma, or DLBCL, patients treated with Regeneron 1979 doses 80 milligrams or higher.

6 月，我們公佈了 Regeneron 1979（我們的 CD20xCD3 雙特異性抗體）的最新療效和安全性數據。Regeneron 1979 在接受過大量預先治療的非何杰金氏淋巴瘤患者中持續顯示出較高的反應率。尤其值得注意的是，我們觀察到 7 例瀰漫性大 B 細胞淋巴瘤 (DLBCL) 患者中有 4 例接受了 Regeneron 1979 劑量 80 毫克或更高劑量的治療，並獲得了完全緩解。

Notably, 4 of these had failed prior CAR-T therapy and 2 of which achieved complete responses. Regeneron 1979 has demonstrated manageable tolerability with no discontinuations due to cytokine release syndrome or neurotoxicity to date.

值得注意的是，其中 4 例患者之前接受過 CAR-T 療法但失敗，而其中 2 例患者獲得了完全緩解。Regeneron 1979 已證明具有良好的耐受性，迄今尚未出現因細胞激素釋放症候群或神經毒性而導致的停藥情況。

Recruitment for a potentially pivotal Phase II trial for Regeneron 1979 is now ongoing. The multi-arm study will enroll several disease-specific cohorts of relapsed/refractory non-Hodgkin's lymphoma patients, including follicular lymphoma, DLBCL and other non-Hodgkin's lymphoma subtypes.

Regeneron 1979 的一項可能具有關鍵意義的 II 期試驗的招募工作正在進行中。這項多臂研究將招募幾組復發/難治性非何杰金氏淋巴瘤患者，包括濾泡性淋巴瘤、瀰漫性大B細胞淋巴瘤和其他非何杰金氏淋巴瘤亞型。

Our 2 other CD3 bispecific antibodies, MUC16xCD3 for platinum-resistant ovarian cancer and BCMAxCD3 for relapsed or refractory multiple myeloma, are in clinical studies that are actively enrolling patients. We plan to present preliminary BCMAxCD3 data by the end of 2019.

我們另外兩種 CD3 雙特異性抗體，即用於治療鉑抗藥性卵巢癌的 MUC16xCD3 和用於治療復發或難治性多發性骨髓瘤的 BCMAxCD3，正在進行臨床研究，並積極招募患者。我們計劃在 2019 年底前公佈 BCMAxCD3 的初步數據。

Finally, recruitment is ongoing for the first costimulatory candidate, Regeneron 5678, which binds prostate-specific membrane antigen, or PSMA, on tumor cells as well as the CD28 costimulatory molecule on T cells. Based on preclinical evidence, we are hoping to see synergy of our costims with Libtayo in disease settings such as prostate cancer that have proven resistant to immunotherapy alone. If successful, this innovative approach could open up the possibility of immunotherapy to a large number of patients who do not currently have this option.

最後，首個共刺激候選藥物 Regeneron 5678 的招募工作正在進行中，該藥物可與腫瘤細胞上的前列腺特異性膜抗原 (PSMA) 以及 T 細胞上的 CD28 共刺激分子結合。根據臨床前證據，我們希望看到我們的共刺激分子與 Libtayo 在前列腺癌等已證明對單獨免疫療法抗藥性的疾病環境中產生協同作用。如果成功，這種創新方法可能會為目前沒有免疫療法選擇的許多患者帶來免疫療法的可能性。

In addition, we expect a number of updates related to other programs emerging for our pipeline. By the end of 2019, we are planning to present our C5 antibody data in patients with paroxysmal nocturnal hemoglobinuria, or PNH. By the end of this year, we also expect readout of our ANGPTL3 antibody Phase III study in homozygous familial hypercholesterolemia as well as a readout of our Activin A antibody pivotal study in the rare disease fibrodysplasia ossificans progressiva, or FOP.

此外，我們預計還將發布一些與我們研發管線中其他項目相關的更新資訊。到 2019 年底，我們計劃公佈我們在陣發性睡眠性血紅蛋白尿症（PNH）患者中的 C5 抗體數據。今年底，我們也將發表 ANGPTL3 抗體治療純合子家族性高膽固醇血症的 III 期研究結果，以及 Activin A 抗體治療進行性骨化性纖維發育不良（FOP）這種罕見疾病的關鍵性研究結果。

Phase III studies of fasinumab, our advanced candidate for osteoarthritis pain, are now fully enrolled, and data are expected during 2020.

我們用於治療骨關節炎疼痛的先進候選藥物 fasinumab 的 III 期研究現已全面啟動，預計將於 2020 年獲得數據。

Finally, we just celebrated the fifth anniversary of the Regeneron Genetic Center. To date, we have sequenced 700,000 individuals linking their exome data with detailed medical records. We continue to be excited about our ongoing effort here, including our work to sequence the UK Biobank database in collaboration with a consortium of leading biopharma partners. Mining of the Regeneron Genetic Center database has already discovered and/or validated a number of genetic drug targets across several human diseases, which are positively impacting our current development efforts.

最後，我們剛剛慶祝了 Regeneron 基因中心成立五週年。到目前為止，我們已經對 70 萬人進行了測序，並將他們的外顯子組數據與詳細的醫療記錄聯繫起來。我們對目前在這裡所做的努力感到興奮，包括與領先的生物製藥合作夥伴聯盟合作，對英國生物銀行資料庫進行測序的工作。對 Regeneron 基因中心資料庫的挖掘已經發現和/或驗證了多種人類疾病的多個基因藥物靶點，這對我們目前的研發工作產生了積極影響。

With that, I'll now turn the call over to Marion.

接下來，我將把電話交給瑪莉安。

Thank you, George. In the second quarter, we executed well across our portfolio of existing lines of business and recent launches.

謝謝你，喬治。第二季度，我們在現有業務線和近期推出的各項業務中都取得了良好的業績。

Starting with EYLEA. Global net product sales grew 13% year-over-year to $1.9 billion. In the U.S., net product sales grew 17% year-over-year and 8% quarter-over-quarter to $1.16 billion. EYLEA growth is driven by share gain and market expansion underpinned by the aging population and increase in diabetes prevalence. In the branded U.S. anti-VEGF market, our share increased to 71% of net product sales.

從愛麗莎開始。全球淨產品銷售額年增 13%，達到 19 億美元。在美國，淨產品銷售額年增 17%，季增 8%，達到 11.6 億美元。安永的成長得益於市場份額的提升和市場擴張，而人口老化和糖尿病盛行率的上升則支撐了這一增長。在美國品牌抗 VEGF 市場中，我們的市佔率成長至淨產品銷售額的 71%。

In the quarter, a temporary shortage of Avastin in select geographies modestly impacted EYLEA net sales. EYLEA continues to help patients with the diabetic eye disease, and this represents an important growth opportunity for the brand.

本季度，部分地區 Avastin 的暫時短缺對安永的淨銷售額產生了輕微影響。EYLEA 持續幫助糖尿病眼疾患者，這對品牌來說是一個重要的成長機會。

In mid-May, the FDA approved EYLEA to treat all stages of diabetic retinopathy, and our launch commenced immediately. For this indication, EYLEA is the only anti-VEGF approved with 2 dosing options, allowing doctors to customize treatment to their patients' needs.

5月中旬，FDA批准EYLEA用於治療所有階段的糖尿病視網膜病變，我們的產品上市工作隨即展開。針對此適應症，EYLEA 是唯一核准的抗 VEGF 藥物，提供 2 種劑量選擇，使醫師能夠根據患者的需求量身訂做治療方案。

Our comprehensive plans to develop EYLEA's position in the diabetic retinopathy market are underway. We began educating both physicians and patients upon approval, encouraging early intervention for appropriate patients and ensuring EYLEA is the first-line anti-VEGF treatment. It's early days in the launch, but we're pleased with feedback from retina specialists, and we're seeing positive early interest and uptake among major practices.

我們正在實施全面的計劃，以提升EYLEA在糖尿病視網膜病變市場的地位。獲得批准後，我們開始對醫生和患者進行教育，鼓勵對合適的患者進行早期幹預，並確保 EYLEA 成為第一線抗 VEGF 治療藥物。雖然產品發布尚處於早期階段，但我們對視網膜專家的回饋感到滿意，並且我們看到主要診所對此表現出了積極的早期興趣和接受度。

We are investing in EYLEA's promotional platforms to advance our market-leading position across all indications, including wet AMD, DME and in diabetic retinopathy. Our expanded and realigned sales force has the dual focus of growing both the diabetic eye disease market and our core wet AMD business. Robust engagement efforts with the retinal community messaging both EYLEA's clinical and real world experience are well underway. Visual outcomes and safety remain the standards by which therapies are compared, and EYLEA's rapid and sustained outcomes in improving and protecting vision are unsurpassed. We're committed to further strengthening our leadership position for EYLEA through continued innovation, including in dose and delivery. Pending FDA approval, the EYLEA prefilled syringe will be launched in 2019.

我們正在投資安永的推廣平台，以鞏固我們在所有適應症（包括濕性 AMD、DME 和糖尿病視網膜病變）中的市場領先地位。我們擴大和重新調整後的銷售團隊的雙重重點是發展糖尿病眼疾市場和我們的核心濕性 AMD 業務。EYLEA 與視網膜社群進行了強而有力的互動活動，向他們宣傳其臨床經驗和真實世界經驗，目前進展順利。視覺效果和安全性仍然是比較各種療法的標準，而 EYLEA 在改善和保護視力方面所取得的快速和持續的效果是無與倫比的。我們致力於透過持續創新，包括劑量和給藥方式的創新，進一步鞏固我們在安樂死領域的領先地位。待FDA批准後，EYLEA預充式註射器將於2019年上市。

I'd now like to turn to Libtayo. The launch in cutaneous squamous cell carcinoma, or CSCC, continues to gain momentum. And in the U.S., net product sales were $41 million for the quarter. Brand awareness within the medical community is growing, demonstrated by the breadth of prescribers at major cancer centers and community practices around the country. Since the launch, we made further progress in establishing Libtayo as the standard of care in advanced CSCC across all lines of therapy.

我現在想轉向Libtayo。皮膚鱗狀細胞癌（CSCC）的治療進展持續加速。在美國，該季度淨產品銷售額為 4,100 萬美元。醫療界對品牌的認知度正在提高，這從全國各大癌症中心和社區診所的處方醫生數量之多可見一斑。自上市以來，我們在確立 Libtayo 作為晚期 CSCC 所有治療方案的標準療法方面取得了進一步進展。

Market research indicates more than 3x as many CSCC patients are now receiving an anti-PD1 or PD-L1 treatment compared to before Libtayo's approval. We believe Libtayo is poised for continued growth. We have broad payer access and a 2A recommendation from the National Comprehensive Cancer Network. Libtayo is the only checkpoint inhibitor to have this designation in CSCC.

市場調查顯示，與 Libtayo 核准前相比，現在接受抗 PD1 或 PD-L1 治療的 CSCC 患者人數增加了 3 倍以上。我們相信Libtayo已做好持續成長的準備。我們擁有廣泛的支付方管道，並獲得了美國國家綜合癌症網絡的 2A 級推薦。Libtayo 是唯一在 CSCC 中獲得此項殊榮的檢查點抑制劑。

Additionally, ex U.S. launches in CSCC are underway, and we look forward to data that could expand the potential of our dermatologic oncology portfolio into earlier stages of CSCC and beyond.

此外，我們正在美國以外的地區推出 CSCC 產品，並期待獲得相關數據，以擴大我們皮膚腫瘤產品組合在 CSCC 早期及以後階段的潛力。

Moving to PRALUENT. In the second quarter, global net sales were $74 million. In the highly competitive U.S. market, we remain focused on patient affordability and physician ease of prescribing. We are working closely with our collaborator, Sanofi, to greatly improve brand profitability.

遷移至 PRALUENT。第二季度，全球淨銷售額為 7,400 萬美元。在競爭激烈的美國市場，我們始終專注於患者的經濟承受能力和醫生開處方的便利性。我們正與合作夥伴賽諾菲緊密合作，以大幅提高品牌獲利能力。

Turning to KEVZARA. In the second quarter, global net sales were $59 million. In the U.S., KEVZARA continues to make headway in the IL-6 subcutaneous class with an estimated 47% share of new patients-dispensed KEVZARA, or NBRx, and 29% share of total scripts OTX.

轉向 KEVZARA。第二季度，全球淨銷售額為 5,900 萬美元。在美國，KEVZARA 在 IL-6 皮下注射劑領域繼續取得進展，據估計，KEVZARA 在新患者處方中佔 47% 的份額（即 NBRx），在總處方中佔 29% 的份額（即 OTX）。

Now for DUPIXENT, which is transforming the lives of patients suffering from the Type 2 inflammatory diseases, atopic dermatitis, asthma and now chronic rhinosinusitis with nasal polyps. Global net product sales in the second quarter were $557 million. In the U.S., net product sales reached $455 million, representing 151% year-over-year growth.

現在，DUPIXENT 正在改變患有 2 型發炎性疾病、異位性皮膚炎、氣喘以及現在的慢性鼻竇炎和鼻息肉的患者的生活。第二季全球淨產品銷售額為 5.57 億美元。在美國，淨產品銷售額達到 4.55 億美元，年增 151%。

Total prescriptions, or TRx, in the U.S. grew approximately 30% compared to the first quarter. This was driven by continued growth in approved indications, adult atopic dermatitis and asthma as well as the launch in atopic dermatitis for adolescents. Weekly new-to-brand prescription, or NBRx, for the second quarter averaged approximately 1,200 patients per week up from 950 in the prior quarter. This momentum is further evidence of the positive impact of our commercialization strategy and execution across all approved indications.

美國處方總量（TRx）比第一季增加了約 30%。這主要得益於核准適應症的持續成長，包括成人異位性皮膚炎和氣喘，以及青少年異位性皮膚炎的上市。第二季每週新開處方（NBRx）平均約為每週 1,200 名患者，高於上一季的 950 名患者。這一勢頭進一步證明了我們的商業化策略和執行在所有已批准的適應症中都產生了積極影響。

As we mentioned last quarter, prescribing continues to grow in adult atopic dermatitis as more moderate patients are just prescribed DUPIXENT and more health care professionals gain brand experience. Our recent launch in adolescents is going well. As a reminder, DUPIXENT is the first biologic approved for adolescents, many of whom remain uncontrolled using topical therapies.

正如我們上個季度提到的，隨著越來越多的中度患者被處方DUPIXENT，以及越來越多的醫療保健專業人員獲得該品牌的使用經驗，成人異位性皮膚炎的處方量持續增長。我們最近針對青少年推出的產品進展順利。需要提醒的是，DUPIXENT 是第一個獲準用於青少年的生物製劑，許多青少年使用局部療法仍無法控制病情。

Market reaction has been extremely positive. Target physicians are prescribing and excited about the results they're seeing. There is significant uptake of both dermatologists and allergists, and we're making meaningful inroads in reaching target pediatric dermatologists and pediatric allergists. In addition, market access coverage is already at or near levels of the adult population.

市場反應極為積極。Target 的醫生們正在開立處方，並且對他們看到的結果感到興奮。皮膚科醫生和過敏科醫生都對此給予了高度評價，我們在接觸目標兒科皮膚科醫生和兒科過敏科醫生方面取得了顯著進展。此外，市場准入覆蓋率已達到或接近成年人口水準。

Asthma is a significant opportunity, and DUPIXENT is well positioned for continued growth. DUPIXENT's differentiated clinical and safety profile continues to support uptake. The asthma biologic market has expanded 13% since DUPIXENT's launch, demonstrating our ability to compete and grow this market.

氣喘是一個重要的市場機遇，DUPIXENT 已做好充分準備，有望持續成長。DUPIXENT 差異化的臨床和安全性特徵繼續支持其市場推廣。自 DUPIXENT 上市以來，氣喘生物製劑市場成長了 13%，這證明了我們有能力在這個市場中競爭並實現成長。

Allergists who have experience using DUPIXENT in atopic dermatitis now also see its benefit for their asthma patients. Prescribing more -- excuse me, prescribing among pulmonologists is also increasing, and they are highly receptive to DUPIXENT's efficacy, use in steroid-dependent patients and self-administration.

有使用 DUPIXENT 治療異位性皮膚炎經驗的過敏症專家現在也看到了它對氣喘患者的益處。肺科醫生開立的處方量也在增加——抱歉，應該說是肺科醫生開具的處方量也在增加，他們對 DUPIXENT 的療效、在類固醇依賴性患者中的應用以及自我給藥方式都非常認可。

And finally, in late June, DUPIXENT became the first biologic medicine approved as an add-on maintenance therapy treatment for adults with inadequately controlled chronic rhinosinusitis with nasal polyps. This indication is yet another first-in-class opportunity for DUPIXENT given the high unmet need.

最後，在 6 月下旬，DUPIXENT 成為首個獲準用於治療成人慢性鼻竇炎伴隨鼻息肉且控制不佳的生物製劑，作為附加維持治療。鑑於目前尚未滿足的巨大需求，此適應症為DUPIXENT提供了另一個同類首創的機會。

In the U.S., up to 90,000 adults with chronic rhinosinusitis with nasal polyps are considered uncontrolled despite prior surgery or systemic corticosteroid use, and about 55,000 patients are those that had a prior surgery. Importantly, many patients with this disease have other Type 2 inflammatory diseases like asthma. In our 2 Phase III clinical trials, almost 60% of patients also had asthma, which was improved with the DUPIXENT treatment.

在美國，有多達 90,000 名患有慢性鼻竇炎和鼻息肉的成年人，儘管之前接受過手術或使用過全身性皮質類固醇，但病情仍未得到控制；其中約有 55,000 名患者是之前接受過手術的患者。值得注意的是，許多患有這種疾病的患者還患有其他 2 型發炎性疾病，如氣喘。在我們進行的 2 項 III 期臨床試驗中，近 60% 的患者還患有氣喘，而 DUPIXENT 治療改善了他們的氣喘症狀。

Our commercial efforts are focused on ENTs and allergists, and we're having constructive payer discussions. While early in the launch, we believe this will be a meaningful growth opportunity for DUPIXENT, and we look forward to providing future updates.

我們的商業努力主要集中在耳鼻喉科醫生和過敏科醫生身上，我們正​​在與支付者進行建設性的討論。雖然目前還處於上市初期，但我們相信這將是 DUPIXENT 的一個重要成長機會，我們期待提供未來的更新資訊。

In closing, we're excited about our near-term performance and confident that our ongoing commercialization efforts will drive long-term growth across core brands and ongoing launches.

最後，我們對近期業績感到興奮，並相信我們正在進行的商業化努力將推動核心品牌和持續推出的產品實現長期成長。

Now I'll turn the call over to Bob.

現在我把電話交給鮑伯。

Thanks, Marion. For the second quarter 2019, Regeneron executed well and delivered solid financial results on both the top and bottom lines. And as Len stated, we are pleased that the Sanofi antibody collaboration has reached commercial profitability.

謝謝你，瑪莉安。2019 年第二季度，Regeneron 公司營運良好，營收和利潤均實現了穩健的財務表現。正如 Len 所說，我們很高興賽諾菲抗體合作計畫已經實現商業獲利。

Total revenues for Regeneron grew 20% year-over-year to $1.93 billion driven by continued growth of our core brands, EYLEA and DUPIXENT.

受核心品牌 EYLEA 和 DUPIXENT 的持續成長推動，Regeneron 的總營收年增 20%，達到 19.3 億美元。

Non-GAAP diluted net income per share grew 10% year-over-year to $6.02 on non-GAAP net income of $690 million. Our second quarter GAAP results were impacted by both the Alnylam upfront payment and the equity investment.

非GAAP稀釋後每股淨收益年增10%至6.02美元，非GAAP淨收益為6.9億美元。我們第二季的 GAAP 業績受到 Alnylam 預付款和股權投資的雙重影響。

In addition to Marion's earlier comments about EYLEA, I want to highlight 2 additional items related to U.S. EYLEA net sales for the quarter. First, inventory movements were immaterial in the quarter. Second, U.S. EYLEA net sales were impacted by an increase in sales-related deductions.

除了 Marion 先前對 EYLEA 的評論之外，我還想重點介紹與 EYLEA 本季度美國淨銷售額相關的另外 2 項內容。首先，本季庫存變動微不足道。其次，美國安怡淨銷售額受到銷售相關扣款增加的影響。

Moving to our collaboration revenue line items. Starting with Bayer. Ex U.S. EYLEA net product sales, which are reported to us by Bayer were $715 million representing a 7% reported and a 13% constant currency basis increase year-over-year. Total Bayer collaboration revenue for the second quarter of 2019 grew 10% year-over-year to $289 million, of which $269 million was derived from our share of net profits from EYLEA sales outside the U.S.

接下來是我們的合作收入明細。從拜耳開始。根據拜耳公司向我們報告，除美國以外，EYLEA淨產品銷售額為7.15億美元，以報告匯率計算年增7%，以固定匯率計算年增13%。2019 年第二季拜耳合作總營收年增 10% 至 2.89 億美元，其中 2.69 億美元來自我們在美國以外地區銷售 EYLEA 產品所獲得的淨利份額。

For the Sanofi collaboration, we generated significantly improved results. Total Sanofi collaboration revenue was $349 million, up 47% year-over-year. This increase was primarily driven by improved profitability in the Sanofi antibody collaboration. In the second quarter of 2019, Regeneron recognized a profit of $39 million in connection with the commercialization of non-I/O antibodies compared to a loss of $69 million in the second quarter of 2018.

在與賽諾菲的合作中，我們取得了顯著的改善成果。賽諾菲合作計畫的總收入為 3.49 億美元，年增 47%。這一成長主要得益於賽諾菲抗體合作計畫的獲利能力提升。2019 年第二季度，再生元公司確認了與非 I/O 抗體商業化相關的 3,900 萬美元利潤，而 2018 年第二季度則虧損了 6,900 萬美元。

Profitability came from higher global net product sales of DUPIXENT partly offset by an increase in commercialization-related expenses to support ongoing DUPIXENT launches. Based on our current projections, we anticipate increasing profitability from the commercialization of non-I/O antibodies going forward.

DUPIXENT 全球淨產品銷售額的成長帶來了盈利，但部分被支持 DUPIXENT 持續上市的商業化相關費用的增加所抵消。根據我們目前的預測，我們預期未來非免疫腫瘤抗體的商業化將帶來更高的獲利能力。

Turning now to expenses. Non-GAAP R&D expenses were $589 million for the second quarter of 2019 compared to $470 million for the second quarter 2018 and essentially flat compared to the $583 million recognized in the first quarter of 2019 driven by continued investment in our research platform and pipeline.

接下來談談費用。2019 年第二季非 GAAP 研發費用為 5.89 億美元，而 2018 年第二季為 4.7 億美元，與 2019 年第一季確認的 5.83 億美元基本持平，這主要得益於我們對研究平台和產品線的持續投資。

Our non-GAAP unreimbursed R&D expense, which is calculated as the total non-GAAP R&D expense less R&D reimbursements from our collaborators, was $423 million for second quarter 2019 compared to $286 million for the second quarter 2018 and $419 million for first quarter 2019. The year-over-year increase is primarily driven by higher spend associated with our earlier-stage pipeline, clinical trial and manufacturing costs to support ongoing development programs and lower Sanofi reimbursement as a result of the amended immuno-oncology discovery and development agreement.

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）在2019年第二季為4.23億美元，而2018年第二季為2.86億美元，2019年第一季為4.19億美元。年比增幅主要由早期研發管線、臨床試驗和生產成本方面的支出增加所致，以支持正在進行的研發項目，以及由於修訂後的免疫腫瘤學發現和開發協議導致賽諾菲報銷減少所致。

Based on the current progress in our R&D pipeline and outlook for the remainder of the year, we are tightening our previous full year 2019 guidance for non-GAAP unreimbursed R&D to $1.625 billion to $1.71 billion.

根據我們研發管線目前的進展以及對今年剩餘時間的展望，我們將先前對 2019 年全年非 GAAP 未報銷研發的預期收緊至 16.25 億美元至 17.1 億美元。

Next, non-GAAP SG&A expense was $375 million for the second quarter of 2019, a 16% year-over-year increase driven by commercialization-related expenses to support ongoing DUPIXENT launches and EYLEA's recent launch in diabetic retinopathy. We are tightening our previous full year 2019 guidance for non-GAAP SG&A to $1.53 billion to $1.58 billion.

其次，2019 年第二季的非 GAAP SG&A 費用為 3.75 億美元，年成長 16%，主要原因是與商業化相關的費用，以支持正在進行的 DUPIXENT 上市和 EYLEA 最近在糖尿病視網膜病變領域的上市。我們將 2019 年全年非 GAAP 銷售、一般及行政費用預期收緊至 15.3 億美元至 15.8 億美元。

Sanofi reimbursement of Regeneron commercialization-related expenses, a line item found within Sanofi collaboration revenue, was $123 million for the second quarter of 2019. We are lowering and tightening our previous full year 2019 guidance for Sanofi reimbursement of Regeneron commercialization-related expenses to $500 million to $530 million.

2019 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 1.23 億美元。我們將先前對賽諾菲 2019 年全年 Regeneron 商業化相關費用報銷的預期下調並收緊至 5 億美元至 5.3 億美元。

Turning now to taxes. For the second quarter, our GAAP effective tax rate was 14.1%. We are reaffirming our full year 2019 GAAP effective tax rate guidance of 11% to 13%.

接下來談談稅務問題。第二季度，我們的 GAAP 有效稅率為 14.1%。我們重申 2019 年全年 GAAP 有效稅率預期為 11% 至 13%。

To assist with modeling, principally due to the Alnylam $400 million upfront exclusion from non-GAAP earnings, the full year 2019 non-GAAP tax rate will be higher than our full year 2019 GAAP effective tax rate.

為了方便建模，主要是由於 Alnylam 4 億美元的預付款從非 GAAP 收益中排除，2019 年全年非 GAAP 稅率將高於我們 2019 年全年 GAAP 實際稅率。

Turning next to our balance sheet and cash flow. Regeneron ended the second quarter with cash and marketable securities of $5.55 billion. Through the first 6 months of the year, we generated free cash flow of $916 million. We calculate free cash flow as net cash provided by operating activities, less capital expenditures.

接下來我們來看資產負債表和現金流量表。再生元公司第二季末持有現金及有價證券55.5億美元。今年前六個月，我們創造了 9.16 億美元的自由現金流。我們將自由現金流計算為經營活動產生的現金流量淨額減去資本支出。

Capital expenditures were $95 million for the quarter and $169 million year-to-date. Based on our updated capital spend plan and year-to-date spending levels, we are lowering and tightening our full year 2019 capital expenditure guidance to $380 million to $420 million.

本季資本支出為 9,500 萬美元，年初至今已支出 1.69 億美元。根據我們更新後的資本支出計畫和年初至今的支出水平，我們將 2019 年全年資本支出指導目標下調並收緊至 3.8 億美元至 4.2 億美元。

In conclusion, we are very pleased with our operational and financial performance this quarter. These financial results along with the execution on our R&D and commercial strategies position us for continued long-term growth.

總之，我們對本季的營運和財務表現非常滿意。這些財務業績，加上我們在研發和商業策略方面的執行，使我們具備了持續長期成長的條件。

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

那麼，我想把電話轉回給賈斯汀。

Thank you, Bob. That concludes our prepared remarks, and we'd now like to open the call for Q&A. (Operator Instructions) Please go ahead, John.

謝謝你，鮑伯。我們的演講稿到此結束，現在我們想開放問答環節。（操作說明）約翰，請開始。

(Operator Instructions) And our first question is from Carter Gould from UBS.

（操作員說明）我們的第一個問題來自瑞銀集團的卡特古爾德。

Congrats on the Sanofi collaboration tipping over into profitability. One for George. I wanted to ask around the CD20 antigen loss you observed at disease progression in some of the patients responding to 1979. I was interested in your current understanding of the mechanism player, given I believe this was rare with rituxan? And how you see this potentially, ultimately influencing, how 1979 maybe positioned in the treatment paradigm?

恭喜與賽諾菲的合作項目轉虧為盈。給喬治的一份。我想詢問一下您在 1979 年觀察到的一些對治療有反應的患者在疾病進展過程中出現的 CD20 抗原流失情況。我對你的機制玩家目前的理解很感興趣，因為我相信這種情況在使用利妥昔單抗時很少見？您認為這可能會對 1979 年在治療模式中的地位產生怎樣的潛在、最終的影響？

I have to admit I didn't quite get your question there.

我得承認，我剛才沒完全理解你的問題。

Okay. It was around the CD20 antigen loss you saw in some of the patients treated, and how you see that ultimately potentially influencing how the drug gets positioned in the treatment paradigm, if it potentially takes away salvage options?

好的。您在一些接受治療的患者中觀察到了 CD20 抗原流失的情況，您認為這最終可能會如何影響該藥物在治療模式中的定位，因為它可能會剝奪一些補救措施？

Right. Well, I think that we have seen antigen loss of both CD20 and also CD19, which has occurred. So far, it doesn't seem to have, in these very late-stage patients, dramatically affected the response rates or the durability. So we're seeing the rates that we responded -- we reported. So it doesn't seem like it's at this point a major issue.

正確的。我認為我們已經觀察到 CD20 和 CD19 抗原的流失，這種情況已經發生。到目前為止，對於這些晚期患者而言，它似乎並沒有顯​​著影響緩解率或療效持久性。所以我們看到了我們回應的比率——我們報告的比率。所以目前看來，這似乎不是一個大問題。

Our next question is from Matthew Harrison from Morgan Stanley.

下一個問題來自摩根士丹利的馬修·哈里森。

I guess I wanted to ask on the initial BCMA data that you expect to present towards the end of this year. I mean how should we think about relevant comparisons here? Is this something you would compare against CAR-T, against BiTEs? I'm just wondering how we should think about that and what the goal here is?

我想問一下您預計在今年年底公佈的BCMA初步數據。我的意思是，我們應該如何考慮這裡相關的比較？你會將這種方法與 CAR-T 療法或 BiTE 療法進行比較嗎？我只是想知道我們應該如何看待這個問題，以及我們的目標是什麼？

Well, I could start and maybe George has more comments, but I would say best thing is probably to wait for the data, but the way Sanofi and Regeneron are thinking about that, and this is part of the collaboration, is that obviously if we can deliver anything close to what a bispecific can deliver, then -- that a CAR-T can deliver, excuse me, then a bispecific being off-the-shelf and a pharmaceutical-like drug, pricing consideration, things like that, should obviously have a huge advantage in the marketplace.

嗯，我可以先說說，也許喬治還有更多評論，但我認為最好的方法可能是等待數據。賽諾菲和再生元正在考慮這個問題，這也是合作的一部分，很明顯，如果我們能提供接近雙特異性抗體療效的療法，那麼——抱歉，CAR-T療法能提供接近雙特異性抗體療效的療法，那麼雙特異性抗體作為一種現成的、類似藥品的藥物，在定價等方面，顯然應該在市場上具有巨大的優勢。

So we would consider our competition more of things like the BiTEs and what have you. Obviously, we have already started out with long-lasting molecules, they're well designed, they -- we make them straightforwardly through the proprietary approach. So we think that we can compete and what you should be looking for is what kind of activity we can deliver. So maybe we should just wait for that.

所以我們認為我們的競爭對手更像是 BiTE 之類的東西。顯然，我們已經開始研發長效分子，它們經過精心設計，我們透過專有方法直接製造它們。所以我們認為我們有能力參與競爭，而您應該關注的是我們能夠提供什麼樣的服務。所以或許我們應該等等看。

Yes. And I think -- just to add that -- I think that obviously, we're hoping that it's going to confirm that our class of CD3 bispecifics are reproducibly sort of top of the class in terms of producing the sort of efficacy that we've already seen with our CD20xCD3 bispecific. And so that's what we're hoping for.

是的。而且我認為——補充一點——顯然，我們希望它能證實，我們的 CD3 雙特異性抗體在產生我們已經在 CD20xCD3 雙特異性抗體中看到的那種療效方面，是可重複地處於領先地位的。所以，這就是我們所希望的。

In addition to that, we just want to point out that both with our own pipeline, and obviously, with our partner's pipeline, there are a myriad of combination opportunities. So it's just sort of the beginning to show the activity with the BCMA bispecific. We can then add to it with the right set of combinations with components that both sides in the collaboration have to offer that we're very excited about, including, for example, our costims, which we have quite a few that could potentially collaborate clinically with the BCMAxCD3 bispecific.

除此之外，我們也要指出，無論是我們自己的產品線，或是我們合作夥伴的產品線，都存在著無數的組合機會。所以這只是展示 BCMA 雙特異性抗體活性的開始。然後，我們可以將其與合作雙方提供的組件進行適當的組合，我們對此感到非常興奮，例如，我們的共刺激分子，我們有很多共刺激分子可以與 BCMAxCD3 雙特異性抗體在臨床上進行協同作用。

Our next question is from Terence Flynn from Goldman Sachs.

下一個問題來自高盛的 Terence Flynn。

Congrats on the antibody JV profitability as well. Maybe just 2 on DUPIXENT. First on, I was wondering if you could share your thoughts about the relevant size of the 6- to 11-year-old population here of atopic derm? And then would the pace of uptake be similar or faster than what we saw with adults in your view?

恭喜抗體合資企業也獲利了。或許只服用2片DUPIXENT。首先，我想請您分享一下您對本地 6 至 11 歲異位性皮膚炎患者群體規模的看法？那麼，您認為兒童的接受速度會和成年人的接受速度相似還是更快呢？

And then on dupi for grass allergy, thanks for the additional data, just wondering next steps there for that program? If you could give us any more color on the forward?

關於杜必利（Dupi）治療草過敏，感謝您提供的補充數據，請問該計畫的下一步計劃是什麼？您能否再透露一些關於前鋒的情況？

So why don't we take the dupi -- Marion will take the commercial question first.

那我們為什麼不先回答這個問題呢——瑪莉安將先回答商業問題。

Sure. And Terence, just to clarify your question on DUPIXENT, you were talking about the European populations or were you talking about U.S. populations?

當然。特倫斯，為了澄清你關於DUPIXENT的問題，你指的是歐洲人群還是美國人群？

Sure. I mean both would be great, but yes, I know you got the data this morning from 6 to 11. And again, I don't think you guys have characterized how big those groups are.

當然。我的意思是兩者都很好，但是，是的，我知道你今天早上 6 點到 11 點之間拿到了數據。而且，我認為你們還沒有明確描述這些群體的規模有多大。

Right, right. So what I wanted to share with you is, obviously, with the atopic dermatitis population in the U.S. for adults, we've said about 300,000 to 400,000 patients are at greatest need of therapy. And I just want to lend the context that at this point, what we're very pleased with, with uptake and the difference that DUPIXENT is making in the lives of patients, we've probably only so far reached about high teens, about 18% of the adult patient population. We're excited about the adolescents launch, and we're seeing nice uptake there, early days, again a lot more work to do. We haven't yet given a characterization in the size of the pediatric population, but certainly will in the future as we get further into the data readouts and preparedness for launch of that indication, which certainly, I can confirm we'll be prepared to launch as soon as we have the FDA approval.

對，對。所以我想和大家分享的是，很顯然，在美國的成人異位性皮膚炎患者中，我們說大約有 30 萬到 40 萬患者最需要治療。我只想補充一點背景信息，目前我們非常滿意的是，DUPIXENT 的普及率以及它給患者生活帶來的改變，但我們可能目前只覆蓋了大約 18% 的成年患者群體。我們對青少年市場的推出感到興奮，我們看到青少年市場反應不錯，但目前還處於早期階段，還有很多工作要做。我們尚未對兒科族群的規模進行描述，但隨著我們進一步了解數據並做好推出該適應症的準備，將來肯定會進行描述。我可以肯定地說，一旦獲得 FDA 的批准，我們將做好推出該適應症的準備。

Just a slight follow up. The uptake of the cream that we -- Eucrisa was fairly brisk, I think, in some of the younger patients. So we think that market is really one of great unmet medical need. And as George said, these are children we studied that had 60% of their body covered with lesions, having all sorts of effect on their mental health, their sleeping, their family, their adjustability to quality of life. So I think that in the severe patients, we would expect a pretty brisk uptake. But it's going to actually take some work because you're treating children with a biologic, we still have to constantly educate and remind people what George said in contradistinction to other biologics where you see an increased infection if you're -- or listen carefully, George mentioned that it was actually a numerically decrease, consistent that we have seen this across our severe and moderately severe atopic dermatitis patients, a numerical decrease. So we think that as people get more and more and more comfortable with the safety and efficacy, this will move lower and lower down into the age groups as we get approval. George maybe you want to turn to the grass allergy and what's next?

補充一點。我認為，我們這款名為 Eucrisa 的乳膏在一些年輕患者中的接受度相當高。所以我們認為這個市場確實存在著巨大的未滿足醫療需求。正如喬治所說，我們研究的這些孩子身上 60% 的皮膚都佈滿了病變，這對他們的心理健康、睡眠、家庭以及生活品質的適應能力都產生了各種各樣的影響。所以我認為，對於重症患者，我們預期藥物吸收速度會相當快。但實際上這需要一些努力，因為用生物製劑治療兒童，我們仍然需要不斷地教育和提醒人們，正如喬治所說，與其他生物製劑不同，如果你仔細聽，就會發現感染率上升——喬治提到，感染率實際上是下降的，這與我們重度和中度重度異位性皮膚炎患者的情況一致，感染率確實下降了。因此我們認為，隨著人們對安全性和有效性的越來越放心，隨著我們獲得批准，這種藥物的適用年齡範圍將會越來越小。喬治，或許你想談談草過敏，接下來該怎麼辦？

Yes. So as I mentioned, we were very excited by the potential of DUPIXENT to apparently increase the tolerability of SCIT therapy. I may have misspoke. Obviously, if there was 25 patients per arm, and I said 30 patients discontinuous -- 30% of the patients discontinued on SCIT, which is, I think, is about normal. Obviously, if you do the math, that's about 8 patients, that's the exact number.

是的。正如我之前提到的，我們對 DUPIXENT 能夠提高 SCIT 療法的耐受性感到非常興奮。我可能說錯話了。顯然，如果每組有 25 名患者，我說有 30 名患者中斷治療——30% 的患者停止了 SCIT 治療，我認為這差不多是正常的。顯然，如果你計算一下，那就是大約 8 位病人，這就是確切的數字。

But in any case, so as we noted, the ability of desensitization therapy to work is real, but it takes time, and it comes at the cost of tolerability in many patients not being able to get through the therapy because of the severe allergic reactions. So it is obviously very exciting to see DUPIXENT have such an apparent benefit, albeit in an early study in small numbers on the tolerability of the SCIT therapy.

但無論如何，正如我們所指出的，脫敏療法確實有效，但這需要時間，而且會造成耐受性差，許多患者由於嚴重的過敏反應而無法完成治療。因此，儘管 DUPIXENT 在早期小樣本 SCIT 療法耐受性研究中顯示出如此明顯的益處，但看到它確實令人非常興奮。

We have a number of other ongoing programs in studying allergy. And I think we're going to be looking at all of these together before we come up with our formal strategy of how to go forward in this. But we do think that this is a very exciting area that can make a lot of difference to a lot of people who are suffering from allergies. So we're pretty excited.

我們還有一些其他正在進行的過敏研究計畫。我認為，在製定正式的推進策略之前，我們會把所有這些因素綜合考慮。但我們認為這是一個非常令人興奮的領域，可以為許多過敏症患者帶來很大的改變。所以我們非常興奮。

Our next question is from Yaron Werber from Cowen.

我們的下一個問題來自 Cowen 公司的 Yaron Werber。

And again, nice results. I have, if you don't mind, just 2 questions, the first one on dupi. If you can just give us a sense across between asthma, AD, and obviously, chronic rhinosinusitis is obviously just getting going, but what really kind of led to the growth this quarter on a quarter-over-quarter basis? And in asthma, where are you getting the majority of sales? Is it new to biologics or is it switching from biologics?

再次，結果很不錯。如果你不介意的話，我只有兩個問題，第一個是關於 dupi 的。如果您能為我們介紹一下氣喘、AD 以及慢性鼻竇炎（顯然慢性鼻竇炎才剛開始發展）之間的情況，那麼是什麼真正導致了本季環比增長呢？在氣喘領域，你們的銷售額大部分來自哪裡？它是生物製劑的新用戶，還是從生物製劑轉而使用生物製劑？

And then just a question on EYLEA whether -- we're hearing some reports on the field that there is now a slightly higher discounting program from Regeneron about a 4% and does that jive with what you're saying?

關於安永（EYLEA）還有一個問題——我們聽到一些報導說，Regeneron公司現在有一個折扣力度稍大的方案，大約是4%，這和您所說的一致嗎？

So before Marion tackles those questions, I'll say it is Justin's first call and maybe he is being nice to you. We said one question per, that was 3. We'll let Marion [give you pass on], then try and deal with these...

所以在 Marion 回答這些問題之前，我想說這是 Justin 的第一個電話，也許他只是對你客氣點。我們說好每人一個問題，總共三個。我們先讓瑪莉安把問題交給你，然後再處理這些問題…

Sure. I'm happy to. So I'm going to start with EYLEA. And let me first comment that we believe that physicians should make the choice on which anti-VEGF therapy they want to select for their patients, and certainly, EYLEA is the standard of care for many prescribers.

當然。我樂意。那麼我就從愛樂（EYLEA）開始吧。首先我想說的是，我們認為醫生應該為他們的患者選擇他們想要選擇的抗 VEGF 療法，當然，EYLEA 是許多處方醫生的標準治療方案。

Further, I'll just say that we're really not commenting on pricing strategy. I'm happy to go onto some of the other items as well. I'll see if I can remember the questions. We haven't given for DUPIXENT, we haven't. It is early days for many of our indications. So we haven't given break out of business by indication because it would be premature. But I think, your question, there were a couple specifics in there that I can give you. You're asking for a characterization in asthma of the types of patients that are being prescribed DUPIXENT, and we are getting the majority of our starts from bionaïve patients. About 80% of our business is patients who are coming onto biologic therapy, and then, of course, the remaining are switches.

此外，我只想說，我們真的不會對定價策略發表評論。我很樂意繼續討論其他一些項目。我看看能不能記住那些問題。我們沒有為DUPIXENT捐款，真的沒有。目前許多指標仍處於早期階段。因此，我們尚未明確表示將暫停營業，因為現在下結論還為時過早。但我認為，對於你的問題，其中包含一些具體細節，我可以告訴你。您要求對接受 DUPIXENT 治療的氣喘患者類型進行描述，而我們的大多數患者都是初次接受 DUPIXENT 治療的患者。我們約 80% 的業務是接受生物療法的患者，當然，剩下的就是轉換療法的患者了。

The characterization I'll give you is that, certainly, for the physicians who are prescribing, both allergists and pulmonologists now, allergists obviously have a lot of experience with DUPIXENT from atopic dermatitis, but we are hearing very positive comments. And it's the differentiation of the clinical profile, the safety, the results they're getting in terms of the patients' ability to breathe more easily and to go about their lives in a normal way, that obviously coupled with the ability for patients to self or have at-home administration. So certainly, asthma was a major contributor to our performance in the quarter, but as was atopic dermatitis, we continue to see substantial growth.

我能給出的描述是，當然，對於現在開處方的醫生，包括過敏科醫生和肺科醫生來說，過敏科醫生顯然有很多使用 DUPIXENT 治療異位性皮膚炎的經驗，但我們聽到的評價非常積極。臨床表現的差異化、安全性、患者呼吸更順暢、恢復正常生活等方面所取得的成果，以及患者能夠自行或在家中進行治療的能力，都反映了這一點。因此，氣喘無疑是本季業績的主要貢獻者，但與異位性皮膚炎一樣，我們也持續看到顯著成長。

And as I mentioned earlier, there is still so much unmet need certainly with adults. And now we're very excited to also be helping those adolescent patients who are very much in need. So I think I would round it all up by saying that it's the combination of indications, the expansion of our platform with DUPIXENT, that is contributing to this strong second quarter performance.

正如我之前提到的，尤其是在成年人中，仍然存在著許多未被滿足的需求。現在我們也非常高興能夠幫助那些急需幫助的青少年患者。所以我認為，總而言之，正是各種適應症的結合，以及我們平台 DUPIXENT 的擴展，才促成了我們第二季強勁的業績。

Yes. Thanks, Marion. I'll just maybe add one thing to emphasize, you said the combination of indications, that's really resonating well for people, for example, who have both asthma and nasal polyps, which is very commonly coexisting or asthma and atopic dermatitis particularly in adolescents is a common coexistence.

是的。謝謝你，瑪莉安。我只想補充一點，您提到了症狀組合，這對某些人來說確實很有共鳴，例如，患有氣喘和鼻息肉的人，這兩種疾病很常見同時存在；或者氣喘和特應性皮膚炎，尤其是在青少年中，也是一種常見的共存情況。

So the ability to treat these comorbidities is a real advantage for our product, and I think the allergists in particular who are the ones in sort of the center point seeing patients who have multiple comorbidities are really getting there.

因此，能夠治療這些合併症是我們產品的一大優勢，我認為過敏科醫生尤其如此，他們處於治療多種合併症患者的核心位置，並且正在真正解決這個問題。

Our next question is from Geoff Porges from SVB Leerink.

我們的下一個問題來自SVB Leerink的Geoff Porges。

Congratulations on the quarter. A lot of things that I could ask questions on, but I'll just ask 1 with 10 subparts. On the 1979 study, George, you mentioned that it's going to enroll both DLBCL and follicular lymphoma, and presumably, also mantle cell. Do you envisage that it could be potentially pivotal in all those NHL subtypes? And will you be enrolling patients who are prior CAR-T failures in that trial?

恭喜你本季取得佳績。有很多事情我可以問，但我只問一個問題，這個問題可以細分為 10 個部分。喬治，你提到 1979 年的研究將納入瀰漫性大 B 細胞淋巴瘤和濾泡性淋巴瘤患者，而且很可能還會納入套細胞淋巴瘤患者。您是否認為它可能對 NHL 的所有亞型都具有潛在的關鍵作用？你們會招募先前接受 CAR-T 療法失敗的患者參與試驗嗎？

Yes. So basically, the way our pivotal Phase II study is designed is with a number of arms, actually each one dedicated precisely to exactly some of those subtypes that you're interested in. So that, yes, each one we would consider to have pending, of course, how active in the data and the durability and so forth, each one would have registrational possibilities. And we also have a -- in the pivotal Phase II, we certainly will have the late-stage follicular lymphoma patients, the late-stage DLBCL patients. But also we have a program where we're focusing on arm, specifically on CAR-T failures where we think obviously in such a high unmet need population where people have failed everything, if one sees the sort of activities that we're seeing in this very small numbers of patients so far being maintained and being durable that, yes, that could also be a separate approval opportunity.

是的。所以基本上，我們關鍵的 II 期研究的設計方式是設定多個分支，實際上每個分支都專門針對您感興趣的某些亞型。所以，是的，我們會考慮每一項都待定，當然，資料活躍度、持久性等等，每一項都有註冊的可能性。而且，在關鍵的 II 期試驗中，我們肯定會納入晚期濾泡性淋巴瘤患者和晚期瀰漫性大B細胞淋巴瘤患者。但我們還有一個項目，重點關注 CAR-T 療法失敗的患者，我們認為，在這樣一個未滿足需求的群體中，人們已經嘗試過所有療法但都失敗了，如果我們看到目前在極少數患者身上觀察到的療效能夠維持並持久，那麼，是的，這也可以是一個單獨的審批機會。

That 2 out of 4 prior CAR-T that George mentioned with complete responses was very encouraging.

喬治提到的先前 4 例 CAR-T 治療中有 2 例獲得了完整的療效，這非常令人鼓舞。

Our next question is from Cory Kasimov from JPMorgan.

我們的下一個問題來自摩根大通的科里·卡西莫夫。

I recognize this is probably a difficult one to answer, but it's -- we're frequently asked it so I'll ask you. Kind of how are you broadly thinking about the longer-term outlook for EYLEA when you balance the possibilities of health care reform and Part B exposure pending competition in wet AMD and then your own new EYLEA launches in less exposed indications?

我知道這個問題可能很難回答，但是──我們常常被問到這個問題，所以我就問你。您如何看待 EYLEA 的長期前景？一方面要考慮醫療改革的可能性，另一方面要考慮 B 部分在濕性 AMD 領域競爭的影響，以及您自己的新 EYLEA 在受影響較小的適應症領域上市。

Yes. Obviously, it is a difficult question to answer, and we hope to give a good answer to it. Our view is more qualitative. If you look at the brand, we're seeing good growth. And the good growth is not just occurring in the United States, it's occurring, I think, it was about 13% outside of the United States. For a brand that's this large and this late in the class that says that the demographics that we predicted would be having a positive impact. So I do think there is plenty of room for growth.

是的。顯然，這是一個很難回答的問題，我們希望能夠給出令人滿意的答案。我們的觀點更偏向定性分析。從品牌角度來看，我們看到了良好的成長動能。而且良好的成長不僅發生在美國，我認為，美國以外的地區也出現了約 13% 的成長。對於一個如此龐大且發展到如此後期的品牌來說，這表明我們預測的人口統計數據將產生積極影響。所以我認為還有很大的發展空間。

In terms of competition, obviously, as -- I think it was mentioned on the call, at the end of the day, vision and maintaining, improving vision is the gold standard. It's what the FDA measures you by. I think it's what most patients care most about, and we are unsurpassed in that.

就競爭而言，顯然，正如——我想在電話會議上提到的——歸根結底，視力以及保持和提高視力才是黃金標準。這是美國食品藥物管理局（FDA）用來衡量你的標準。我認為這是大多數患者最關心的問題，而我們在這方面無人能及。

On long-term safety, I think we've given over 25 million injections. We are expecting action on our prefilled syringe, which we've worked hard at to come up -- PDUFA date is coming up pretty soon. So our enormous safety database is, I think, going to work in our favor.

從長期安全性來看，我認為我們已經進行了超過2500萬次注射。我們期待預充式註射器能有所進展，我們為此付出了很多努力——PDUFA 日期很快就要到了。所以我認為，我們龐大的安全資料庫將會對我們有利。

It is hard to do this, and you're injecting 20 -- as we said now, up to 25 million injections into the eye, you have to be able to do that in a very reliable and safe way.

這樣做很困難，正如我們剛才所說，你要向眼睛注射多達 2000 萬次——高達 2500 萬次——你必須能夠以非常可靠和安全的方式完成這項工作。

If you look at some of the studies out there that have been focusing on, let's say, dryness, there's also, if you look at them, there's some data that's worth inspecting on the reactions in terms of inflammation. So we'll have to see how that all sorts out. Plus we have the advantage of being able to give the dose monthly as well as every other month as well as all the indications. So I think we're well positioned for the near term.

如果你看看一些研究，比如說，那些關注乾燥問題的研究，你會發現，其中也有一些關於發炎反應的數據值得研究。所以，我們得看看事情最終會如何發展。此外，我們還可以根據所有適應症，每月或每兩個月給予一次劑量。所以我認為我們短期內處於有利地位。

In terms of your question about health care policy and the overhang, obviously, we watch that carefully. We're very involved in Washington. We know what's really important to us. We are sympathetic to the notion that some have that prices in the United States are much higher than prices for the same drugs outside the United States, but we don't think that the solution of tying prices in the United States for a drug like EYLEA, where we don't control the price outside of the United States, makes a lot of sense. That would be a huge negative to the biotechnology industry as a whole because so many biotechnology companies license away their rights for survival outside the United States, and they don't control the prices. So we were happy to see in the Grassley-Wyden compromise that, that was not in there. It almost got in there, in a [firm way] that it couldn't happen that vote was 14 and 14. We watched that carefully. We're working at it. And so we're hopeful that the policy debates that have taken place will not block innovation or reward the good actors. We haven't had a price increase in EYLEA. So the notion of having an inflation rebate would not affect us.

關於您提出的醫療保健政策及其潛在影響的問題，顯然，我們會密切關注。我們非常積極地參與華盛頓的事務。我們知道什麼對我們來說才是真正重要的。我們理解有些人認為美國藥品的價格比美國以外同類藥品的價格高得多，但我們認為，對於像 EYLEA 這樣的藥品，如果美國無法控制其在美國以外的價格，那麼將美國的價格與美國以外的價格掛鉤的解決方案就沒什麼意義。這對整個生技產業來說將是一個巨大的負面影響，因為許多生技公司為了在美國以外生存而將其權利轉移出去，而且它們也無法控制價格。所以我們很高興地看到，在格拉斯利-懷登妥協方案中，沒有包含這一項。它幾乎以[堅定的方式]表明，投票結果不可能是14比14。我們仔細觀察了這一點。我們正在努力。因此，我們希望已經進行的政策辯論不會阻礙創新，也不會獎勵那些表現優異的企業。EYLEA的產品價格並沒有上漲。所以，通貨膨脹退稅的概念不會對我們產生影響。

So maybe that's a qualitative summary of all the things that we worry about. We worry about competition obviously, we worry about the environment, we worry about the regulatory and patent exclusivity and so forth.

所以，這或許可以概括我們所有擔憂的事情。我們當然會擔心競爭，我們會擔心環境，我們會擔心監管和專利獨佔等等。

There's one item. I might pick up on one thread in the question, and this was just related to EYLEA and our indications, and obviously, the growing indications with recently launching in diabetic retinopathy. Today, 60% of our sales are now coming from wet AMD. And with the expansion of our diabetes indications, now over 30% of EYLEA sales are coming from the diabetes indications, and of course, recently including diabetic retinopathy and the balance for others.

只有一件物品。我可能會就這個問題中的一個線索展開討論，這與 EYLEA 及其適應症有關，顯然，最近在糖尿病視網膜病變領域推出的適應症也在不斷增加。如今，我們 60% 的銷售額都來自濕式 AMD。隨著我們糖尿病適應症的擴大，目前 EYLEA 超過 30% 的銷售額來自糖尿病適應症，當然，最近也包括了糖尿病視網膜病變，其餘部分則來自其他適應症。

And our next question is from Evan Seigerman from Crédit Suisse.

下一個問題來自瑞士信貸的埃文·塞格曼。

Congrats on the progress. One combo for Bob and Marion. So Bob, you had mentioned that there was some sort of an Avastin shortage that may have benefited EYLEA sales in the quarter. And then more broadly speaking, how are you positioning EYLEA in light of upcoming competitive launches?

恭喜你取得進展。鮑伯和瑪莉安的一套組合。鮑勃，你之前提到過，阿瓦斯汀（Avastin）出現了一些短缺，這可能對安理國際（EYLEA）本季的銷售額有所幫助。更廣泛地說，鑑於即將推出的競爭產品，您如何定位安樂死？

Sure. So let me take a start and then if Bob has elements to add. So I think, first, when we talk a little bit about the second quarter, we certainly had a strong quarter. It was influenced by a few factors, and let me cover those.

當然。那麼，我先開始吧，然後如果鮑伯還有什麼要補充的。所以我覺得，首先，當我們稍微談談第二季時，我們確實度過了一個強勁的季度。這受到幾個因素的影響，讓我來一一介紹。

Certainly, there is a market expansion in consideration. We do see growth from our wet AMD and DME indications. We began launching in diabetic retinopathy. As mentioned, we added customer-facing personnel to focus on our diabetes indications. There was a modest, what we had characterized as a modest impact from Avastin shortages in some geographies in the U.S. And then as well, we were up against a somewhat weaker 2018 second quarter comparison. So I did want to give some relative context there.

當然，市場擴張正在考慮中。我們看到，在濕性老年黃斑部病變和糖尿病黃斑水腫（DME）適應症方面，我們的產品確實實現了成長。我們最初是從糖尿病視網膜病變領域開始的。如前所述，我們增加了面向客戶的人員，專注於糖尿病適應症。在美國部分地區，阿瓦斯汀短缺造成了一定程度的影響，正如我們之前所描述的。此外，我們也面臨 2018 年第二季業績相對疲軟的局面。所以我想提供一些相關的背景資訊。

I think, in terms of, as we look forward, we do think that for EYLEA, as a standard of care with 8 years in market, it's important to look at growth rates as the average of several quarters to get a true sense of what the growth profile has looked like historically and may go in the future.

我認為，展望未來，對於安怡（EYLEA）這款上市 8 年的護理標準產品而言，重要的是要將增長率作為幾個季度的平均值來考察，以便真正了解其歷史增長情況以及未來的發展趨勢。

And then in terms of preparation for competitive launches, we feel very well positioned to continue to perform well in the market with EYLEA, and certainly, we're very excited about the breadth of indications and the profile that Len just covered related to EYLEA.

至於為應對競爭性產品上市所做的準備，我們感覺已經做好了充分的準備，能夠憑藉 EYLEA 繼續在市場上取得良好表現。當然，我們對 Len 剛才提到的 EYLEA 的適應症範圍和產品概況感到非常興奮。

Our next question is from Yatin Suneja from Guggenheim Partners.

我們的下一個問題來自古根漢合夥公司的亞廷·蘇內賈。

Congrats on all the progress. The question is on REGN3500, the IL-33 antibody that you have, could you maybe talk about the development strategy there. Given that dupi monotherapy was numerically better than IL-33 across all the endpoints that you evaluated in the asthma trial, could you maybe comment on the areas where you think IL-13 might play a differentiated role relative to dupi?

祝賀你們取得的所有進展。關於您擁有的 IL-33 抗體 REGN3500，您能否談談它的研發策略？鑑於在氣喘試驗中，dupi 單藥治療在數值上優於 IL-33，您能否就您認為 IL-13 相對於 dupi 可能發揮不同作用的領域發表一些評論？

Well as you say, the hope would be that there might be particular patients who might better respond to, for example, or would like the alternative in IL-33 as opposed to a dupi in asthma. And of course, we're also waiting for upcoming data from our atopic dermatitis program and also from our COPD program to really understand how we're going to position this. But we do think that this could be an important alternative option for some patients with asthma, just based on the current data, and we're waiting for more data to see how it evolves.

正如你所說，希望是某些特定患者可能對IL-33等藥物反應更好，或更喜歡用IL-33代替氣喘藥物。當然，我們也在等待來自異位性皮膚炎計畫和慢性阻塞性肺病計畫的最新數據，以便真正了解我們將如何定位這項研究。但根據目前的數據，我們認為這可能是某些氣喘患者的重要替代選擇，我們正在等待更多數據來觀察其發展。

Our next question is from Mohit Bansal from Citigroup.

下一個問題來自花旗集團的莫希特·班薩爾。

A quick question on PRALUENT. Given that the challenges you are facing in the market, do you think there comes a point where you and your partner take a tough [personal] decision? Or you think you can turn it around and achieve profitability for this drug in longer term?

關於 PRALUENT 的一個簡短問題。鑑於你們在市場上面臨的挑戰，你認為你和你的伴侶會不會在某個時刻做出艱難的（個人）決定？還是你認為你能扭轉局面，使這種藥物在長期內獲利？

Yes. Obviously, this is a highly competitive space. And we don't want to get too detailed about what our strategies are. Obviously, we said we're trying to match our investments appropriately, but we do have some strategies. At the end of the day, heart disease is still a major killer. The PCSK9 is still a terrific drug. So maybe that's all we should say at this point.

是的。顯然，這是一個競爭非常激烈的領域。我們不想過度透露我們的策略細節。顯然，我們說過我們會努力使我們的投資與目標相匹配，但我們確實有一些策略。歸根結底，心臟病仍然是主要的致命原因之一。PCSK9 仍然是一種非常有效的藥物。所以，或許我們現在該說的話了。

Our next question is from Kennen MacKay from RBC Capital Markets.

下一個問題來自加拿大皇家銀行資本市場的 Kennen MacKay。

Maybe one for George. I was wondering if you can just comment a little bit more on the high-dose aflibercept trials you're initiating? And sort of how high you can go on those and really what the goals of the high-dose treatment are?

或許給喬治準備一個。我想請您再詳細介紹一下您正在進行的高劑量阿柏西普試驗？那麼，這些藥物的劑量最高能達到多少呢？高劑量治療的真正目標是什麼？

Well, obviously, from our earlier studies we've seen that about 50% of patients can do well with a more prolonged dosing schedule that is on a 12-week interval. And so we are imagining that if we go to a higher dose of aflibercept, we may be able to push a higher percentage of patients to either a 12-week or maybe even a 16-week regimen. So we're running the studies to actually test these longer intervals and see whether the higher doses will actually do that. So we'll see.

顯然，從我們先前的研究中，我們發現大約 50% 的患者可以透過 12 週為間隔的更長給藥方案獲得良好的治療效果。因此我們設想，如果我們提高阿柏西普的劑量，或許能讓更高比例的患者接受 12 週甚至 16 週的療程。所以我們正在進行研究，以實際測試這些更長的間隔時間，看看更高的劑量是否真的能達到這種效果。我們拭目以待。

Our next question is from Alethia Young from Cantor Fitzgerald.

我們的下一個問題來自 Cantor Fitzgerald 公司的 Alethia Young。

Congrats on a very good quarter. I guess I found the 18% or so number very striking about how much penetration you've had in adults and maybe can you talk about some of the things that you're doing to drive penetration or is it the slow but sure process to get more people on the drug?

恭喜你本季業績非常出色。我覺得你們在成人中的普及率達到 18% 左右這個數字非常驚人，你們能談談為了提高普及率你們做了哪些工作嗎？還是說，讓更多人使用這種藥物是一個緩慢但穩定的過程？

Sure. So this -- I believe your question, Alethia, is in reference to the comment on DUPIXENT in adult atopic dermatitis. And I do -- yes, just to give context, but my comment is to make the point that while certainly many adults that had very, very difficult moderate-to-severe disease are now being treated, there is tremendous potential for us to do more with DUPIXENT to help appropriate adults in need of therapy.

當然。所以——我相信你的問題，Alethia，是指關於 DUPIXENT 在成人異位性皮膚炎中的應用的評論。是的，我只是想提供一些背景信息，但我的評論是為了說明，雖然現在很多患有非常非常嚴重的重度中度疾病的成年人正在接受治療，但我們利用 DUPIXENT 為需要治療的合適成年人做更多的事情，還有巨大的潛力。

And to your characterization, I do think that DUPIXENT is gaining momentum in atopic dermatitis, certainly in other indications as well. And it's not unusual for physicians first to prescribe to those patients who are their toughest patients, the most severe patients. We're seeing pickup in breadth and depth of physician prescribing of DUPIXENT, and we also are seeing more moderate, moderate-to-severe patients being treated. So it's encouraging because DUPIXENT is helping these patients in a way that we hear time and time again is transformational to their lives and as well transformational to the lives of the physicians who are treating them.

至於你所描述的情況，我認為DUPIXENT在異位性皮膚炎領域正在獲得發展勢頭，當然在其他適應症方面也是如此。醫生先給那些最難治、病情最嚴重的病人開藥的情況並不少見。我們看到醫生開 DUPIXENT 處方的範圍和深度都在增加，我們也看到更多中度、中重度患者接受了治療。所以這令人鼓舞，因為 DUPIXENT 正在幫助這些患者，我們一次又一次地聽到，它改變了他們的生活，也改變了治療他們的醫生的生活。

Our next one is from Hartaj Singh from Oppenheimer & Co.

接下來是來自奧本海默公司的哈塔吉·辛格。

I just have one question on Libtayo. You had a stronger number than we expected for the second quarter. I think this PD-1 has gotten some really good data, and just from what we've heard, is being really accepted broadly. Can you just give some color on the commercial rollout and how that is progressing? And any thoughts also on the lung cancer projects you've got ongoing?

關於Libtayo，我只有一個問題。你們第二季的業績比我們預期的還要好。我認為這款 PD-1 已經獲得了一些非常好的數據，而且就我們目前所聽到的情況來看，它正被廣泛接受。能否簡單介紹一下商業推廣的進展？對於您目前正在進行的肺癌研究項目，您有什麼想法嗎？

So I will give some comment related to commercial performance. And with Libtayo, we certainly are making inroads to become the standard of care for CSCC patients as described in our label. Approximately 90% of new patient starts in CSCC within the anti-PD-1, PD-L1 class are now going to Libtayo. Further, we have excellent payer coverage that has already been achieved, and we'll -- further, we'll have our permanent J-code in October 1. So certainly, we've made a strong start in the launch of CSCC for Libtayo.

因此，我將就商業表現方面發表一些評論。而有了 Libtayo，我們無疑地正在朝著成為 CSCC 患者的標準治療方案的目標邁進，正如我們的藥品說明書中所述。目前，大約 90% 的新 CSCC 患者開始接受抗 PD-1、PD-L1 類藥物治療時，都會選擇 Libtayo。此外，我們已經實現了出色的支付方覆蓋，而且我們將在 10 月 1 日獲得永久 J 代碼。因此，毫無疑問，我們在 Libtayo 的 CSCC 啟動方面取得了強勁的開端。

About the lung cancer, I guess, early on, there were a lot of thoughts that the PD-1 space would be commoditized and that there would be so many PD-1s and it'd be sort of boilerplates just to make another one. I think that if one fairly looks at the data, these are not behaving the same, and that's obvious for sure in the lung cancer space where KEYTRUDA is the unquestioned leader. And so we're very excited about the fact that we think that our PD-1 might have very good activities, it's already demonstrated, as we've heard, in certain settings. So we're excited to see how it's going to perform in the lung cancer setting and whether it will be one of the rare PD-1s that can really provide a lot of benefit to patients there.

關於肺癌，我想，早期有很多人認為 PD-1 領域會商品化，會出現很多 PD-1 藥物，而這些藥物都會變成千篇一律的模板，只是為了製造另一個藥物而已。我認為，如果客觀地看待這些數據，就會發現它們的表現並不相同，這一點在肺癌領域尤其明顯，KEYTRUDA 在該領域是無可爭議的領導者。因此，我們非常興奮地認為，我們的 PD-1 可能具有非常好的活動效果，正如我們所知，它已經在某些環境中得到了證明。因此，我們很興奮地想看看它在肺癌治療中的表現，以及它是否會成為少數幾種能夠真正為肺癌患者帶來巨大益處的 PD-1 抑制劑之一。

And our last question from Brian Skorney from Baird.

最後一個問題來自 Baird 公司的 Brian Skorney。

Two quick ones. Obviously, bevacizumab is the most prescribed VEGF therapy despite being off-label. It looks like there is one company planning on actually filing a BLA next year to market a branded bevacizumab. How do you guys think about the market impact of an active sales force marketing bevacizumab versus the more path if use it right now?

兩個簡短的問題。顯然，儘管貝伐珠單抗屬於超適應症用藥，但它仍然是處方量最大的 VEGF 治療藥物。看來有一家公司計劃明年提交生物製品許可申請 (BLA)，以銷售品牌化的貝伐珠單抗。你們覺得積極組成銷售團隊推廣貝伐單抗的市場影響，與現在就使用這種藥物相比，哪種方式更能吸引消費者？

And then just real quickly on Regeneron 4461. I know leptin was a pretty well researched target about a decade ago, never quite realized the [terms]. Can you just share your thoughts on what makes targeting the receptor with your antibody attractive? And how it could overcome some of the prior history?

然後簡單說說 Regeneron 4461。我知道大約十年前瘦素是一個研究相當深入的目標，但我從未真正理解[術語]。您能否分享一下您認為用抗體靶向受體的優勢所在？它又將如何克服之前的一些歷史遺留問題？

Sure, just very briefly because we're running out of time, I'll take the bevacizumab question and George will deal with the question on the insulin -- I mean on the leptin receptor.

好的，因為時間不多了，我就簡單說一下，我來回答關於貝伐珠單抗的問題，喬治會回答關於胰島素──我是說關於瘦素受體的問題。

So in terms of bevacizumab, obviously you can't have a biosimilar to bevacizumab in terms of approvals just because it doesn't have any approvals. So somebody if they want to get approvals, are obviously going to have to do all the different studies, et cetera. And we already know that in large studies conducted independently by the government, for example, Protocol T, bevacizumab was inferior -- clearly inferior to EYLEA.

所以就貝伐單抗而言，顯然你不能有貝伐單抗的生物類似藥獲得批准，因為它沒有任何批准。所以，如果有人想要獲得批准，顯然就必須進行各種不同的研究等等。我們已經知道，在政府獨立進行的大型研究中，例如T方案，貝伐單抗的效果較差──明顯不如EYLEA。

So I think that the use of bevacizumab is mainly one driven by its off-label exceedingly low price. So having another competition there with or without a sales force, as the doctors are well aware about this, we wouldn't expect to have a major impact than the market.

所以我認為貝伐珠單抗的使用主要是由於其超低價格的標籤外使用所致。因此，無論有沒有銷售團隊，再次出現競爭對手，醫生們對此都非常清楚，我們預期不會對市場產生重大影響。

George, on the leptin receptor?

喬治，關於瘦素受體？

Well, just to remind you, one of the major problems with leptin and metreleptin as it was developed was that it elicited unfortunately in quite a significant percentage of patients' antibodies against the leptin. And a lot of these patients are patients who actually still have endogenous leptin activity. So when the antibodies come onboard, the patients end up not only neutralizing the injected leptin but their endogenous leptin, they end up being worse off than they were beforehand, and they were also left with nothing to actually being available to treat them because you now can't give them leptin.

提醒一下，瘦素和美替利汀在研發過程中遇到的一個主要問題是，不幸的是，它在相當大比例的患者體內引發了針對瘦素的抗體。而許多這類患者其實仍具有內源性瘦素活性。因此，當抗體出現時，患者不僅會中和注射的瘦素，還會中和自身內源性瘦素，結果病情比以前更嚴重，而且由於無法再給他們注射瘦素，實際上也沒有任何藥物可以治療他們。

So of course, we are pursuing our leptin receptor-activating antibody in that setting, but it would also provide a better alternative and would allow broader usage. There are other settings where one could have conceived using metreleptin except one would have not wanted to elicit this antibody response and have the potential to wipe out the endogenous leptin remaining activity. And so people were reticent to explore it more broadly in other settings.

所以，我們當然會在這種情況下研究我們的瘦素受體活化抗體，但它也會提供更好的替代方案，並允許更廣泛的應用。在其他情況下，人們可能會使用美替林來受孕，但那樣做就不希望引發這種抗體反應，並有可能消除內源性瘦素的剩餘活性。因此，人們不願在其他環境中更廣泛地探索它。

So on top of that, it is one of the first examples of our new activating antibody technology that allows us to, we hope, create efficient in vivo acting -- activating antibodies for growth factors and cytokines and so forth.

此外，這也是我們新型活化抗體技術的首批實例之一，我們希望能夠利用該技術創造出高效的體內作用——用於生長因子和細胞激素等的活化抗體。

So for all those reasons, we're pretty excited about our leptin receptor program. But of course, we'll be starting in the same sort of rare patients where leptin is mostly used right now.

綜上所述，我們對瘦體素受體計畫感到非常興奮。當然，我們會從目前瘦素主要使用的這類罕見患者開始。

I will now turn the call back over to Justin Holko for closing remarks.

現在我將把電話交還給賈斯汀·霍爾科，請他作總結發言。

Great. Thank you, everyone, and thank you again for dialing in to the call today. The IR team will be around to answer your questions later today.

偉大的。謝謝大家，再次感謝大家今天撥入電話會議。投資者關係團隊稍後會解答您的問題。

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

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