雷傑納榮製藥 (REGN) 2018 Q1 法說會逐字稿

Welcome to the Regeneron Pharmaceuticals First Quarter 2018 Earnings Conference Call. My name is Jason, and I will be your operator. (Operator Instructions)

歡迎參加 Regeneron Pharmaceuticals 2018 年第一季財報電話會議。我叫傑森，我將是你的接線生。（操作說明）

Also, please note this conference is being recorded.

另外，請注意本次會議正在錄影。

And I'll now turn the call over to Manisha Narasimhan, Head of Investor Relations. You may begin.

現在我將把電話交給投資人關係主管瑪妮莎‧納拉辛漢。你可以開始了。

Thank you, Jason. Good morning, and welcome to Regeneron Pharmaceuticals First Quarter 2018 Conference Call.

謝謝你，傑森。早安，歡迎參加 Regeneron Pharmaceuticals 2018 年第一季電話會議。

An archive of this webcast will be available on our website under Events for 30 days.

本次網路直播的存檔將在我們網站的「活動」欄位下保留 30 天。

Joining me on the call 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, Senior Vice President and Chief Financial Officer.

今天與我一起參加電話會議的有：創始人、總裁兼首席執行官 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；以及高級副總裁兼首席財務官 Bob Landry。

After our prepared remarks, we will open the call for Q&A.

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 today include forward-looking statements about Regeneron. Such statements may include, but are not limited to those related to Regeneron and its products and business, financial forecasts and guidance, development programs and related anticipated milestones, collaborations, finances, regulatory matters, intellectual property, pending litigation and competition. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement. A more complete description of these and other material risks can be found in Regeneron's filings with the United States' Securities and Exchange Commission, or SEC, including its Form 10-Q for the quarter ended March 31, 2018, which will be filed with the SEC later today.

我還要提醒各位，今天電話會議上發表的言論包含 Regeneron 的前瞻性陳述。此類聲明可能包括但不限於與 Regeneron 及其產品和業務、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、智慧財產權、未決訴訟和競爭相關的聲明。每項前瞻性聲明都存在風險和不確定性，可能導致實際結果和事件與該聲明中預測的結果和事件有重大差異。有關這些及其他重大風險的更完整描述，請參閱 Regeneron 向美國證券交易委員會 (SEC) 提交的文件，包括截至 2018 年 3 月 31 日的季度 10-Q 表格，該表格將於今天晚些時候提交給 SEC。

Regeneron does not undertake any obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise. In addition, please note that GAAP and non-GAAP measures will be discussed in 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. Once our call concludes, Bob Landry and the IR team will be available to answer further questions.

Regeneron公司不承擔任何公開更新任何前瞻性聲明的義務，無論是由於新資訊、未來事件或其他原因。此外，請注意，今天的電話會議將討論 GAAP 和非 GAAP 指標。有關我們使用非公認會計準則財務指標以及這些指標與公認會計準則的調節表的信息，請參閱我們的財務業績新聞稿，該新聞稿可在我們的網站上查閱。通話結束後，鮑伯·蘭德里和投資者關係團隊將回答進一步的問題。

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

接下來，我將把電話交給我們的總裁兼執行長倫·施萊弗博士。

Thank you, Manisha. Good morning to everyone who has joined us on today's call and webcast.

謝謝你，瑪妮莎。各位早安，感謝你們今天參加電話會議和網路直播。

In my prepared remarks, I will focus on Regeneron's high-level strategy. George will provide details on how our R&D prowess enables and supports that strategy. Marion will update you on the status of our commercialization efforts, which will drive the realization of our strategy. And Bob will recap our financial results.

在我的演講稿中，我將重點放在再生元公司的高層策略。喬治將詳細介紹我們的研發實力如何實現和支持這項策略。Marion 將向您報告我們商業化工作的最新進展，這將推動我們策略的實現。鮑伯將總結我們的財務表現。

Let me begin with EYLEA. EYLEA has been a very successful product both in terms of how much value it brings to patients with vision-threatening retinal diseases as well as how much value it brings to our business. Since approval in late 2011, EYLEA has taken over as the market-leading FDA-approved anti-VEGF agent for retinal diseases. More than 15 million doses of EYLEA have been administered globally since launch. During the first quarter of 2018, global net sales of EYLEA were $1.6 billion. Clearly, at the moment, EYLEA is our most important product. And naturally, many of our shareholders have questions about the sustainability of the EYLEA franchise over the near and long term.

讓我先從EYLEA說起。EYLEA 是一款非常成功的產品，無論從它為患有威脅視力的視網膜疾病的患者帶來的價值，還是從它為我們的業務帶來的價值來看，都是如此。自 2011 年底獲得批准以來，EYLEA 已成為治療視網膜疾病的市場領先的 FDA 批准的抗 VEGF 藥物。自上市以來，全球已接種超過1500萬劑EYLEA疫苗。2018 年第一季度，安樂的全球淨銷售額為 16 億美元。顯然，目前EYLEA是我們最重要的產品。當然，我們的許多股東都對EYLEA特許經營權在近期和長期內的可持續性存在疑問。

We believe that while competition is expected in the anti-VEGF space around late 2019, the therapeutic profile of EYLEA sets a very high bar, and there are no products in late-stage development to our knowledge that are likely to have substantially differentiated product profile from EYLEA.

我們認為，雖然預計到 2019 年底抗 VEGF 領域將會出現競爭，但 EYLEA 的治療效果樹立了非常高的標桿，據我們所知，目前還沒有任何處於後期開發階段的產品可能具有與 EYLEA 有實質差異的產品特性。

In addition, we see significant opportunities for growth based upon the aging of the population as well as the unfortunate but dramatic increase in the prevalence of diabetes. While EYLEA is well penetrated in wet age-related macular degeneration, there remains a large untapped opportunity in diabetic eye disease. That is why we are focused on expanding our indications in diabetic retinal diseases.

此外，人口老化以及糖尿病盛行率不幸但急劇上升，也帶來了巨大的成長機會。雖然 EYLEA 在濕性老年黃斑部病變中滲透良好，但在糖尿病眼部疾病方面仍有很大的未開發機會。這就是為什麼我們致力於擴大我們在糖尿病視網膜疾病領域的適應症。

Currently, EYLEA is indicated for the treatment of diabetic macular edema, where we are the market-leading branded anti-VEGF supported by the NIH-sponsored Protocol T study. Many diabetic patients can also suffer from eye disease without having diabetic macular edema. And much of this results from a condition called diabetic retinopathy without macular edema. Some of these patients are at high risk of suffering from catastrophic vision-threatening complications.

目前，EYLEA 適用於治療糖尿病性黃斑水腫，我們是市場領先的品牌抗 VEGF 藥物，並得到了美國國立衛生研究院 (NIH) 資助的 Protocol T 研究的支持。許多醣尿病患者即使沒有糖尿病黃斑水腫，也可能患有眼部疾病。其中大部分是由一種稱為糖尿病視網膜病變（無黃斑水腫）的疾病引起的。這些患者中有一部分人極有可能遭受危及視力的災難性併發症。

Later this year, we plan to submit an sBLA for approval in diabetic retinopathy without DME based upon the striking initial results that were observed with EYLEA in the PANORAMA study at 6 months. We also look forward to longer-term results from the PANORAMA study, where we will be evaluating the ability of EYLEA to prevent vision-threatening complications.

今年晚些時候，我們計劃根據 EYLEA 在 PANORAMA 研究中 6 個月時觀察到的顯著初步結果，提交 sBLA 申請，以獲得用於治療無 DME 的糖尿病視網膜病變的批准。我們也期待 PANORAMA 研究的長期結果，我們將在其中評估 EYLEA 預防威脅視力的併發症的能力。

But the success of EYLEA creates a challenge for Regeneron to diversify its revenue and profit base. I am pleased to say that we can now see the strategy we put in place, many years ago, starting to bear fruit. Our strategy was and continues to be to invest heavily in our internal research capabilities rather than look externally for new products. Though we do strategically combine our research capabilities with partners, such as Intellia, Alnylam and others, to collaboratively create new product opportunities.

但EYLEA的成功給Regeneron帶來了挑戰，使其收入和利潤來源多元化。我很高興地說，我們現在可以看到，我們多年前製定的策略開始取得了成效。我們的策略過去是、現在仍然是大力投資內部研發能力，而不是向外部尋求新產品。儘管如此，我們還是會與 Intellia、Alnylam 等合作夥伴進行策略性的研究能力結合，以共同創造新的產品機會。

So where do we stand? From a broad perspective, our strategy is working. We have 6 approved FDA medicines and 17 different product candidates in clinical development, all arising from our internal discovery efforts.

那我們現在的處境如何？從整體來看，我們的策略是有效的。我們有 6 種 FDA 批准的藥物和 17 種不同的候選產品正在進行臨床開發，所有這些都源自於我們內部的研發工作。

But in terms of the specific near-term evidence of success from this strategy, I would like to highlight 2 areas: allergic diseases and immuno-oncology. Our efforts to tackle allergic diseases began decades ago and resulted in Dupixent, a true pipeline in a product.

但就該策略在近期取得的具體成功證據而言，我想重點介紹兩個領域：過敏性疾病和免疫腫瘤學。我們致力於解決過敏性疾病的努力始於幾十年前，並最終研發了 Dupixent，這是一條真正意義上的產品線。

Dupixent is currently approved for adults with moderate-to-severe atopic dermatitis, and the launch in the United States is going quite well. We and our collaborator Sanofi are in the midst of launching Dupixent for atopic dermatitis in the rest of the world, which represents another very significant opportunity.

Dupixent 目前已獲準用於治療中度至重度異位性皮膚炎成人患者，在美國的上市進展相當順利。我們和我們的合作夥伴賽諾菲正在世界其他地區推出用於治療異位性皮膚炎的 Dupixent，這代表著另一個非常重要的機會。

Moreover, we are in the process of completing trials that would support the expansion of Dupixent into adolescent and pediatric patients with atopic dermatitis, which once again is another substantial opportunity. But atopic dermatitis may be just the tip of the allergic iceberg. Because we are seeing strong clinical evidence that Dupixent is active in a number of different allergic or so-called type 2 diseases, we believe there is a remarkably broad and deep pipeline within Dupixent itself. And we, along with our collaborator Sanofi, have committed the resources necessary to fully execute our development plan for Dupixent.

此外，我們正在完成一些試驗，這些試驗將支持將 Dupixent 推廣到患有異位性皮膚炎的青少年和兒童患者中，這又是一個重要的機會。但異位性皮膚炎可能只是過敏的冰山一角。由於我們看到了強有力的臨床證據表明 Dupixent 對多種不同的過敏性疾病或所謂的 2 型疾病有效，因此我們相信 Dupixent 本身就擁有非常廣泛和深入的研發管線。我們與合作夥伴賽諾菲一起，投入了必要的資源，以全面執行 Dupixent 的開發計劃。

We anticipate regulatory approval in asthma later this year and have Phase III trials underway in adolescent and pediatric patients with atopic dermatitis, pediatric patients with asthma as well as adults with nasal polyps. Top line data from the Phase III nasal polyps study and the adolescent atopic dermatitis study are expected later this year. In addition, in the second half of this year, we plan to begin pivotal studies in COPD, another very large opportunity. We will also initiate a late-stage program in eosinophilic esophagitis and a Phase II program in peanut and grass allergies later this year.

我們預計今年稍後將獲得氣喘治療的監管批准，目前正在對患有異位性皮膚炎的青少年和兒童患者、患有氣喘的兒童患者以及患有鼻息肉的成年人進行 III 期試驗。預計今年稍後公佈 III 期鼻息肉研究和青少年異位性皮膚炎研究的主要數據。此外，今年下半年，我們計劃啟動 COPD 的關鍵性研究，這是另一個非常大的機會。今年晚些時候，我們還將啟動嗜酸性食道炎的後期研究計畫和花生及草過敏的 II 期研究計畫。

Finally, we will be studying the potential of combining our IL-3 -- IL-33 antibody with Dupixent in several of these allergic or type 2 indications.

最後，我們將研究將我們的 IL-3 -- IL-33 抗體與 Dupixent 聯合用於治療幾種過敏或 2 型疾病的潛力。

In our view, the potential for the Dupixent pipeline is analogous to what happened when it was realized that the anti-TNFs were not just drugs for rheumatoid arthritis but drugs for many different diseases involving overactivity of type 1 immunity.

我們認為，Dupixent 的研發潛力類似於人們意識到抗 TNF 藥物不僅適用於類風濕性關節炎，也適用於許多涉及 1 型免疫過度活躍的不同疾病時所發生的情況。

We believe that the evidence thus far is compelling that Dupixent is not just a drug for atopic dermatitis but has the potential to address multiple other allergic or type 2 diseases. In short, we think that Dupixent may be able to bend the arc of allergic disease.

我們認為，目前的證據足以證明，Dupixent 不僅僅是一種治療異位性皮膚炎的藥物，而且還有潛力治療多種其他過敏性疾病或 2 型疾病。簡而言之，我們認為 Dupixent 或許能夠扭轉過敏性疾病的進程。

Now let's turn to another pillar of our diversification strategy and that is the area of immuno-oncology. Let me be clear, our goal is to become a major player in this space, and we believe that we have the science, tools, technologies, and most importantly, the product candidates to compete and win. Immuno-oncology has transformed the treatment of cancer and is turning out to be one of the largest commercial opportunities in the history of the biopharmaceutical industry.

現在讓我們來看看多角化策略的另一個支柱領域，那就是免疫腫瘤學領域。讓我明確一點，我們的目標是成為這個領域的主要參與者，我們相信我們擁有參與競爭並取得成功所需的科學、工具、技術，以及最重要的——候選產品。免疫腫瘤學改變了癌症的治療方式，並且正在成為生物製藥行業歷史上最大的商業機會之一。

For example, the sales of anti-PD-1 antibodies across a number of cancers are currently at a $12 billion global annual run rate and still growing, driven in large part by use in non-small cell lung cancer.

例如，目前抗 PD-1 抗體在多種癌症中的全球年銷售額已達 120 億美元，並且仍在增長，這在很大程度上是由非小細胞肺癌的應用所推動的。

Our strategy, in this important therapeutic area, has proven to be spot on, in terms of the selection of molecular targets, engineering of complex drug candidates and the selection of the right initial disease states for development.

在這一重要的治療領域，我們的策略已被證明是完全正確的，包括分子標靶的選擇、複雜候選藥物的工程設計以及選擇合適的初始疾病狀態進行開發。

In terms of targets, we chose PD-1 over PD-L1 and that turns out to be the right choice in our opinion based upon the available data.

就靶點而言，我們選擇了 PD-1 而不是 PD-L1，根據現有數據，我們認為這是一個正確的選擇。

Moreover, we leveraged our VelocImmune technology to select an excellent antibody, and our clinical group selected a previously overlooked cancer, cutaneous squamous cell carcinoma or CSCC.

此外，我們利用 VelocImmune 技術篩選出優秀的抗體，我們的臨床團隊則選擇了一種先前被忽視的癌症—皮膚鱗狀細胞癌（CSCC）。

Cemiplimab, our PD-1 antibody has produced breakthrough data in CSCC, and we are awaiting FDA action for this important indication. The response rates we have seen are amongst the highest reported for solid tumor and served as the basis for our breakthrough designation by the FDA. While CSCC is a significant opportunity by itself, non-small cell lung cancer is the largest indication where we are currently studying cemiplimab. Our positive early data from a small cohort of patients with advanced non-small cell lung cancer supports our decision to aggressively move forward in multiple settings of this disease. These data will be presented at the upcoming annual ASCO conference. Our first-line lung cancer study, comparing cemiplimab monotherapy to chemotherapy, is on track to complete enrollment around the end of this year or early next year. We except cemiplimab to be the foundation of our immuno-oncology efforts for years to come.

我們的 PD-1 抗體 Cemiplimab 在 CSCC 治療中取得了突破性進展，我們正在等待 FDA 對此重要適應症採取行動。我們所觀察到的反應率在實體瘤治療中名列前茅，並成為我們獲得 FDA 突破性療法認定的依據。雖然 CSCC 本身就是一個重要的機會，但非小細胞肺癌是我們目前正在研究 cemiplimab 的最大適應症。我們從一小群晚期非小細胞肺癌患者中獲得的積極早期數據支持了我們積極推進該疾病多種治療方案的決定。這些數據將在即將召開的ASCO年會上公佈。我們正在進行第一線肺癌研究，比較 cemiplimab 單藥治療與化療，預計今年底或明年年初完成入組。我們預計 cemiplimab 將成為我們未來幾年免疫腫瘤學研究的基礎。

Another component of our immuno-oncology strategy is our bispecific platform. We are combining our biological and technical capabilities to build molecules that combine tumor targeting and effective functions.

我們免疫腫瘤學策略的另一個組成部分是我們的雙特異性平台。我們正在結合自身的生物學和技術能力，建構兼具腫瘤靶向性和有效功能的分子。

Our CD20xCD3 bispecific antibody, entirely owned by Regeneron, is now making excellent progress in the clinic. You will hear more about this from George at an upcoming medical meeting.

我們完全由 Regeneron 公司擁有的 CD20xCD3 雙特異性抗體目前在臨床試驗中取得了顯著進展。你將在即將召開的醫學會議上從喬治那裡聽到更多相關資訊。

Other bispecifics include MUC16xCD3 and BCMAxCD3, both of which we anticipate advancing into the clinic this year.

其他雙特異性抗體包括 MUC16xCD3 和 BCMAxCD3，我們預計這兩種抗體今年都會進入臨床試驗階段。

Additional CD3 bispecifics are moving towards the clinic, and over the course of this year, we will be giving you information about a new class of bispecific antibodies.

其他 CD3 雙特異性抗體正在向臨床方向發展，今年我們將向您介紹一類新的雙特異性抗體。

Much like Dupixent, we believe that cemiplimab has the potential to be a pipeline within a molecule. And we believe our bispecific platform is able to produce a steady stream of new drug candidates as well. Perhaps most importantly, we see strong potential for combination treatments involving our PD-1 antibody and our bispecifics.

與 Dupixent 類似，我們認為 cemiplimab 有潛力成為分子內部的一個研發管線。我們相信，我們的雙特異性抗體平台也能夠持續不斷地產生新的候選藥物。或許最重要的是，我們看到了將我們的 PD-1 抗體和雙特異性抗體結合起來進行聯合治療的巨大潛力。

So to recap, we believe EYLEA has meaningful additional opportunity for continued growth. Our diversification strategy is clearly on track to deliver the full potential of the Dupixent pipeline and our immuno-oncology franchises, which position us well to continue commercial success. And we will continue to aggressively move the rest of our deep pipeline along as well.

綜上所述，我們認為安樂死還有很大的持續成長機會。我們的多元化策略顯然正按計劃推進，將充分發揮 Dupixent 產品線和免疫腫瘤產品線的潛力，這將使我們處於有利地位，並繼續取得商業成功。我們將繼續積極推進其他深水管道項目的建設。

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

那麼，我把電話交給喬治吧。

Thank you, Len, and good morning to everyone.

謝謝你，Len，大家早安。

The first quarter of 2018 has been very busy and productive from an R&D perspective, and I will provide some of the key highlights.

從研發角度來看，2018 年第一季非常忙碌且成果豐碩，我將介紹一些關鍵亮點。

Beginning with EYLEA, we reported positive data from the Phase III PANORAMA study in diabetic retinopathy. In this study, at 24 weeks, 58% of patients receiving EYLEA experienced a 2-step or greater improvement from baseline on the diabetic retinopathy severity scale compared to 6% of patients receiving sham injection, with a p-value of less than 0.0001. No new safety signals were observed. Importantly, this was the first time that any therapy demonstrated the ability to reverse disease progression in a study specifically designed to evaluate patients with moderately severe to severe nonproliferative diabetic retinopathy without diabetic macular edema.

從 EYLEA 開始，我們報告了糖尿病視網膜病變 III 期 PANORAMA 研究的積極數據。在這項研究中，24 週時，接受 EYLEA 治療的患者中有 58% 在糖尿病視網膜病變嚴重程度評分上較基線改善了 2 級或更多，而接受假注射的患者中只有 6% 達到這一改善，p 值小於 0.0001。未發現新的安全訊號。重要的是，這是首次有療法在一項專門設計用於評估中度至重度非增殖性糖尿病視網膜病變（無糖尿病黃斑水腫）患者的研究中，證明其能夠逆轉疾病進展。

We will continue to evaluate these patients for longer durations to determine whether EYLEA treatment can prevent progression to neovascular vision-threatening complications and also to diabetic macular edema. We expect to make a regulatory submission in the United States later this year.

我們將繼續對這些患者進行更長時間的評估，以確定 EYLEA 治療是否可以預防新生血管性視力威脅併發症以及糖尿病黃斑水腫的發生。我們預計將於今年稍後向美國監管機構提交申請。

In March, at the annual meeting of the American College of Cardiology, we reported positive data from the 18,000 patient cardiovascular outcome study of Praluent, which compared Praluent to maximally tolerated statins. These data showed that Praluent significantly reduced the risk of major adverse cardiovascular events, or MACE, in these high-risk patients and was associated with a lower rate of all-cause death. Safety was consistent with previous trials and no new safety issues were observed.

今年 3 月，在美國心臟病學會年會上，我們報告了 Praluent 的 18,000 名患者心血管結局研究的積極數據，該研究將 Praluent 與最大耐受劑量的他汀類藥物進行了比較。這些數據表明，Praluent 顯著降低了這些高風險患者發生重大不良心血管事件（MACE）的風險，並且與全因死亡率降低有關。安全性與先前的試驗結果一致，未發現新的安全性問題。

In a prespecified analysis, the patients with baseline LDL cholesterol levels, at or above 100 milligrams per deciliter, experienced more pronounced benefit from Praluent, reducing the risk of MACE by 24% and the risk of death from coronary heart disease by 28%. In additional post hoc analyses of this prespecified group, Praluent was associated with a 29% lower risk of death from any cause. These results are consistent with the recently published meta-analysis in the Journal of the American Medical Association that showed an association between more intensive LDL cholesterol lowering and a greater reduction in the risk of total and cardiovascular mortality in patients whose baseline LDL cholesterol was greater than 100 mg per deciliter. We expect a regulatory submission to the FDA based on these data around the middle of the year.

在預先設定的分析中，基線 LDL 膽固醇水平為 100 毫克/分升或以上的患者從 Praluent 中獲益更為明顯，MACE 風險降低了 24%，冠心病死亡風險降低了 28%。在對該預先指定的群體進行的額外事後分析中，Praluent 與任何原因導致的死亡風險降低 29% 相關。這些結果與最近發表在《美國醫學會雜誌》上的薈萃分析一致，該分析表明，對於基線 LDL 膽固醇大於 100 毫克/分升的患者，更積極的 LDL 膽固醇降低與總死亡率和心血管死亡率風險的更大降低之間存在關聯。我們預計將在年中左右根據這些數據向FDA提交監管申請。

Len has shared our enthusiasm for the Dupixent pipeline. Our regulatory submission for Dupixent for the treatment of uncontrolled asthma in adults and adolescents is currently under review by the FDA, with a PDUFA date in October. Detailed results from the Phase III QUEST and VENTURE asthma studies will be presented at the upcoming meeting of the American Thoracic Society. Our Phase III study of asthma in the pediatric setting is currently underway. We also have 3 ongoing Phase III studies of Dupixent in adolescent and pediatric atopic dermatitis. The first of these in adolescents between the ages of 12 and 17 years old is fully enrolled, and we expect to report top line data shortly. 2 pediatric studies: one in children aged 6 to 11 years old, and the second, in children aged 6 months to 5 years old, are currently enrolling. Based on the scientific pathway, we believe that dupilumab could be used in a variety of additional allergic or so-called type 2 immune conditions. We expect to report top line data from 2 Phase III studies of dupilumab in nasal polyps later this year.

Len 和我們一樣對 Dupixent 的研發管線充滿熱情。我們針對成人和青少年未控制氣喘的 Dupixent 的監管申請目前正在接受 FDA 的審查，PDUFA 日期為 10 月。QUEST 和 VENTURE III 期氣喘研究的詳細結果將在即將召開的美國胸腔科協會會議上發表。我們目前正在進行針對兒童氣​​喘的 III 期研究。我們目前還有 3 項針對青少年和兒童異位性皮膚炎的 Dupixent III 期研究正在進行中。第一個針對 12 至 17 歲青少年的試驗已經全部招募完畢，我們預計很快就會公佈初步數據。目前正在進行兩項兒科研究：一項針對 6 至 11 歲的兒童，另一項針對 6 個月至 5 歲的兒童。根據科學路徑，我們認為度普利尤單抗可用於治療多種其他過敏性疾病或所謂的 2 型免疫疾病。我們預計今年稍後公佈 dupilumab 治療鼻息肉的 2 項 III 期研究的主要數據。

We plan to initiate, later this year, a study in patients with comorbid conditions as well as our Phase III programs of dupilumab in COPD and in eosinophilic esophagitis.

我們計劃在今年稍後啟動一項針對合併症患者的研究，以及我們針對 COPD 和嗜酸性食道炎的 dupilumab III 期計畫。

We also plan to launch Phase II studies of dupilumab in peanut and grass allergies in 2018.

我們也計劃於 2018 年啟動 dupilumab 治療花生和草過敏的 II 期研究。

Let me remind you that the human genetic findings from our Regeneron Genetics Center, together with our preclinical studies, support the hypothesis that blocking interleukin-33 might have additional benefits for some patients being treated with dupilumab in some of these diseases.

我想提醒各位，我們 Regeneron 遺傳學中心的人類遺傳學研究成果，以及我們的臨床前研究，都支持這樣一種假設：對於某些疾病患者而言，阻斷白細胞介素-33 可能具有額外的益處，尤其是在接受 dupilumab 治療的情況下。

A Phase II study in asthma of REGN3500, our fully human interleukin-33 antibody, with and without dupilumab, is enrolling patients. We plan to initiate, in the second half of this year, Phase II studies of IL-33 in atopic dermatitis and COPD.

我們正在進行一項針對氣喘患者的 II 期研究，研究 REGN3500（一種全人源白細胞介素-33 抗體）聯合或不聯合度普利尤單抗的療效。我們計劃在今年下半年啟動 IL-33 治療異位性皮膚炎和 COPD 的 II 期研究。

As you also heard from Len, one of the most important areas of our focus is the exciting field of immuno-oncology, where we have multiple approaches towards harnessing the immune system to fight cancer, founded on opportunities provided by our PD-1 antibody and by our emerging portfolio of bispecific antibodies.

正如您從 Len 那裡聽到的，我們重點關注的領域之一是令人興奮的免疫腫瘤學領域，我們擁有多種利用免疫系統對抗癌症的方法，這些方法建立在我們 PD-1 抗體和我們正在開發的雙特異性抗體產品組合所提供的機會之上。

Let me remind you that despite the excitement surrounding the PD-1 pathway, there have also been some sobering realizations. Early on, many thought that the PD-1 pathway blockade would be commoditized, with a prevailing view that there would be many equivalent agents approved. As it now stands, many believe that antibodies against PD-1 are differentiated and more active than those against the PD-L1 ligand. Moreover, out of the 2 approved PD-1 antibodies, only one has been approved as monotherapy in first-line non-small cell lung cancer.

我想提醒各位，儘管 PD-1 通路令人興奮，但也存在一些令人清醒的認知。在早期，許多人認為 PD-1 通路阻斷劑將會商品化，普遍認為會有許多等效藥物獲得批准。目前，許多人認為抗 PD-1 抗體與抗 PD-L1 配體的抗體相比，具有差異性且活性更高。此外，在已獲批准的 2 種 PD-1 抗體中，只有一種被批准作為一線非小細胞肺癌的單藥療法。

Finally, the PD-1 pathway has not demonstrated profound activity in many of the most prevalent cancer settings, including breast cancer, prostate, colorectal, pancreatic and others. And even in settings like lung cancer, where the drug is active, most of the patients still do not respond. Obviously, there is much room to provide much more benefit to many more patients in need.

最後，PD-1 路徑在許多最常見的癌症類型中並未表現出顯著的活性，包括乳腺癌、前列腺癌、大腸直腸癌、胰腺癌等。即使在肺癌等藥物有效的情況下，大多數患者仍然沒有反應。顯然，我們還有很大的空間為更多有需要的患者提供更多益處。

Later this year, with the PDUFA date in October, we anticipate having the third FDA approved PD-1 antibody, cemiplimab, which would be the first approval in our comprehensive immuno-oncology development program. In addition to monotherapy opportunities with cemiplimab, we believe cemiplimab will be the bedrock upon which we plan to build additional combination therapies.

今年晚些時候，隨著 10 月的 PDUFA 日期臨近，我們預計將迎來第三款 FDA 批准的 PD-1 抗體 cemiplimab，這將是我們綜合免疫腫瘤學開發計劃中的第一個獲批產品。除了 cemiplimab 的單藥治療機會外，我們相信 cemiplimab 將成為我們計劃建立其他聯合療法的基石。

We have reported positive data for cemiplimab in metastatic and locally advanced cutaneous squamous cell carcinoma, where we observed an overall response rate of around 47%, which is among the highest response rates seen in any solid malignancy to date with a PD-1 antibody. Cutaneous squamous cell carcinoma will be the first indication for which we anticipate the approval of cemiplimab.

我們已報告了 cemiplimab 在轉移性和局部晚期皮膚鱗狀細胞癌中的積極數據，我們觀察到總緩解率約為 47%，這是迄今為止 PD-1 抗體在任何實體惡性腫瘤中觀察到的最高緩解率之一。皮膚鱗狀細胞癌將是 cemiplimab 核准的首個適應症。

At the upcoming annual ASCO meeting, we look forward to sharing with you additional data in patients with unresectable metastatic cutaneous squamous cell carcinoma. We will also be presenting the activity and durability from our pivotal Phase II cutaneous squamous cell carcinoma study. Importantly, we're also conducting studies in additional tumor types, including first- and second-line non-small cell lung cancer and cervical cancer.

在即將召開的 ASCO 年會上，我們期待與您分享更多關於無法切除的轉移性皮膚鱗狀細胞癌患者的數據。我們還將展示我們關鍵的 II 期皮膚鱗狀細胞癌研究的活性和持久性。重要的是，我們也正在對其他腫瘤類型進行研究，包括第一線和二線非小細胞肺癌和子宮頸癌。

As Len mentioned, first-line non-small cell lung cancer is one of the most exciting opportunities for PD-1 blockade, but only one agent has demonstrated convincing monotherapy activity in this setting. Our program includes 3 key trials, which if successful, could position cemiplimab as a major competitor in this space.

正如 Len 所提到的，一線非小細胞肺癌是 PD-1 阻斷療法最令人興奮的機會之一，但目前只有一種藥物在這種治療環境中表現出令人信服的單藥治療活性。我們的專案包括 3 項關鍵試驗，如果成功，cemiplimab 將成為該領域的主要競爭者。

The first study is cemiplimab monotherapy versus chemotherapy in patients who express PD-L1 of 50% or greater. This study is ongoing, and we expect enrollment to be completed later this year or early next year. The second trial of cemiplimab in combination with chemotherapy, with or without ipilimumab, versus chemotherapy alone in patients with PD-L1 expression of 50% or lower, this study is currently enrolling.

第一項研究是比較 cemiplimab 單藥治療與化療在 PD-L1 表達為 50% 或更高的患者中的療效。這項研究正在進行中，我們預計將於今年稍後或明年年初完成招募工作。目前正在進行第二項試驗，研究 cemiplimab 合併化療（含或不含 ipilimumab）與單獨化療在 PD-L1 表達低於 50% 的患者中的療效比較。

Cemiplimab, in combination with ipilimumab, with or without chemotherapy, in patients with 50% or greater PD-L1 expression, this study would also include a pembrolizumab comparator arm. We plan to initiate this study around midyear.

本研究將採用 Cemiplimab 合併 ipilimumab，不論是否合併化療，用於治療 PD-L1 表達 50% 或以上的患者，同時設立 pembrolizumab 對照組。我們計劃在年中左右啟動這項研究。

Turning to our bispecific antibody platform, which provides monotherapy opportunities as well as opportunities to combine with cemiplimab. Our lead molecule of CD20xCD3 bispecific continues to progress in the clinic. We would like to remind you that this is a wholly owned molecule. This molecule could compete in indications where CD20 antibodies, such as rituximab, are no longer efficacious as well as where CD20 antibodies are currently the standard of care.

接下來，我們將介紹我們的雙特異性抗體平台，該平台既提供了單藥治療的機會，也提供了與 cemiplimab 聯合治療的機會。我們的先導化合物 CD20xCD3 雙特異性分子在臨床試驗中持續取得進展。我們想提醒您，這是我們完全擁有的分子。這種分子可以在 CD20 抗體（如利妥昔單抗）不再有效的適應症以及 CD20 抗體目前是標準療法的適應症中與之競爭。

As we reported at ASH last November, at doses of 5 milligrams or greater, we observed 50% response rates and almost 80% disease control rates in heavily pretreated rituximab refractory patients with non-Hodgkin's lymphoma without any dose-limiting toxicities. And thus we were reporting that we were continuing to dose escalate our CD20 bispecific. At higher doses, we are now seeing encouraging signs of increased activities without any dose-limiting toxicities, and we have not yet reached maximally tolerated dose. We look forward to sharing more data at upcoming medical conference in the second half of this year.

正如我們在去年 11 月的 ASH 會議上報道的那樣，在 5 毫克或更高劑量下，我們觀察到，對於接受過大量利妥昔單抗治療的非霍奇金淋巴瘤難治性患者，有效率達到 50%，疾病控制率接近 80%，且沒有任何劑量限制性毒性。因此，我們報告說，我們將繼續增加 CD20 雙特異性抗體的劑量。在高劑量下，我們現在看到了令人鼓舞的跡象，表明活性有所提高，且沒有任何劑量限制性毒性，而且我們還沒有達到最大耐受劑量。我們期待在今年下半年即將舉行的醫學會議上分享更多數據。

We believe our bispecific platform has the potential to deliver additional clinical candidates, including 2, which are expected to enter the clinic later this year, our MUC16xCD3 and our BCMAxCD3 bispecifics. We're also advancing a new class of bispecific antibodies and hope to share more with you about this new class of bispecifics later this year.

我們相信，我們的雙特異性平台有潛力提供更多臨床候選藥物，包括預計今年稍後進入臨床的 2 個候選藥物，即我們的 MUC16xCD3 和 BCMAxCD3 雙特異性抗體。我們也正在推動一類新型雙特異性抗體的研發，並希望在今年稍後與您分享更多關於這類新型雙特異性抗體的資訊。

Turning now to fasinumab, our NGF antibody for pain. An independent data monitoring committee evaluated the ongoing safety and efficacy of the clinical trials and recommended that the higher dose regimens be discontinued based on their risk-benefit assessment and that the program continue with lower dose regimens. We are modifying the studies accordingly. We're anticipating sharing top line results from the ongoing Phase III study later this year.

接下來我們來談談法西單抗，這是一種用於治療疼痛的 NGF 抗體。獨立的數據監測委員會評估了臨床試驗的持續安全性和有效性，並根據其風險效益評估建議停止較高劑量方案，並建議該計畫繼續採用較低劑量方案。我們正在據此修改研究方案。我們預計將於今年稍後公佈正在進行的 III 期研究的主要結果。

In the interest of time, I will not talk about many of the remaining programs in our pipeline. Addressing diseases ranging from an ultrarare condition, such as fibrodysplasia ossificans progressiva to highly prevalent conditions involving muscle wasting and metabolic disorders.

為了節省時間，我不會談論我們正在籌備中的其他許多項目。治療的疾病範圍很廣，從極為罕見的疾病（如進行性骨化性纖維發育不良）到非常普遍的疾病（如肌肉萎縮和代謝紊亂）。

Please refer to our Form 10-Q, which has a description of all of our clinical programs.

請參閱我們的 10-Q 表格，其中描述了我們所有的臨床項目。

I will now turn the call over to Marion.

現在我將把通話轉給瑪莉安。

Thank you, George, and good morning, everyone. It's a pleasure to be on the call today. This is my first earnings call with Regeneron, and it is a privilege to be part of this wonderful team.

謝謝你，喬治，大家早安。今天能參加這次電話會議真是太好了。這是我第一次參加 Regeneron 的財報電話會議，能夠成為這個優秀團隊的一員，我感到非常榮幸。

I'd like to start with EYLEA, where global net sales in the first quarter were $1.6 billion. EYLEA continues to be the market-leading branded anti-VEGF for retinal diseases in the United States. In the U.S., EYLEA net sales were $984 million, which represented about 70% of the overall branded market. Our dollar share of the branded market increased slightly year-over-year.

我想先從安樂（EYLEA）說起，該公司第一季的全球淨銷售額為 16 億美元。在美國，EYLEA 仍然是治療視網膜疾病的市場領先的品牌抗 VEGF 藥物。在美國，EYLEA 的淨銷售額為 9.84 億美元，約佔整個品牌市場的 70%。我們在品牌市場中的美元份額同比增長略有增長。

Based on a survey we conducted in the first quarter, we estimate that currently about 70% of U.S. EYLEA net sales come from wet AMD and about 25% from DME, with the balance coming from other smaller indications. With the aging of our population and the dramatic increase in the prevalence of diabetes, we expect significant future market growth.

根據我們第一季進行的一項調查，我們估計目前美國 EYLEA 淨銷售額約 70% 來自濕性 AMD，約 25% 來自 DME，其餘部分來自其他較小的適應症。隨著人口老化和糖尿病盛行率的急劇上升，我們預計未來市場將顯著增長。

Looking ahead, we see 2 major opportunities to grow the EYLEA franchise. The first is through additional indications, such as diabetic retinopathy, where we recently reported positive Phase III data from PANORAMA study and expect to make a regulatory submission later this year. If approved, in diabetic retinopathy, we expect that EYLEA could be used in the full spectrum of patients with diabetic eye diseases. Secondly, diabetic eye diseases are dramatically underdiagnosed and undertreated; and even when treated, it is frequently with sub-optimal therapy. This is true both for patients suffering from diabetic macular edema as well as from diabetic retinopathy.

展望未來，我們看到了發展 EYLEA 特許經營權的 2 個主要機會。首先是透過其他適應症，例如糖尿病視網膜病變，我們最近公佈了 PANORAMA 研究的積極 III 期數據，並預計今年稍後向監管機構提交申請。如果獲得批准，我們預計 EYLEA 可用於治療糖尿病視網膜病變，並可用於治療所有患有糖尿病眼部疾病的患者。其次，糖尿病眼疾的診斷率和治療率都非常低；即使接受治療，也常常是次優治療。對於患有糖尿病性黃斑水腫和糖尿病性視網膜病變的患者來說，情況都是如此。

We expect that our increased provider and patient outreach and education could result in more patients with DME being diagnosed and receiving therapy in the near term and similarly impacts diabetic retinopathy following potential approval in this indication. There are also many ongoing efforts both from academia and the industry to develop approaches to identify these patients before they go on to suffer catastrophic vision loss.

我們預計，透過加強對醫療服務提供者和患者的宣傳和教育，近期內將有更多患有 DME 的患者得到診斷和治療，並且在糖尿病視網膜病變獲得潛在批准後，也將產生類似的影響。目前，學術界和工業界都在努力開發各種方法，以便在這些患者遭受災難性視力喪失之前識別出他們。

A further opportunity to strengthen the EYLEA value proposition is through dosing flexibility. EYLEA is currently approved for use on a monthly and every 8-week basis. And we have submitted an application to the FDA for every 12-week dosing in patients with wet AMD with a PDUFA date -- FDA PDUFA date in August 2018.

透過彈性的給藥方式，可以進一步加強安永的價值主張。EYLEA 目前獲準每月使用一次，或每 8 週使用一次。我們已向 FDA 提交申請，要求對患有濕性 AMD 的患者進行每 12 週一次的給藥，並確定 PDUFA 日期——FDA PDUFA 日期為 2018 年 8 月。

We recognize that each patient requires a tailored-treatment regimen, and therefore, if this every 12-week label addition is approved, EYLEA will be the only approved drug in wet AMD to have the flexibility to optimally treat patients regardless of whether they require fixed interval dosing of 4, 8 or 12 weeks. We remind you that our Phase III wet AMD studies, patients were extended to the 12-week dosing interval only after they successfully met treatment goals in more frequent dosing intervals.

我們認識到每位患者都需要量身定制的治療方案，因此，如果每 12 週增加一次的標籤獲得批准，EYLEA 將成為唯一獲批用於治療濕性 AMD 的藥物，無論患者需要 4 週、8 週還是 12 週的固定間隔給藥，EYLEA 都能靈活地提供最佳治療。我們提醒您，在我們的 III 期濕性 AMD 研究中，患者只有在更頻繁的給藥間隔下成功達到治療目標後，才會將給藥間隔延長至 12 週。

Turning now to Dupixent, global net sales in the first quarter of 2018, as recorded by our collaborator Sanofi were $131 million with U.S. net sales of $117 million. Underlying demand continues to be strong with total prescriptions as well as the number of patients on treatment up approximately 25% sequentially from the last quarter. Over 500 new patients were added each week during the quarter. Moreover, we consistently see high persistence rate with over 90% of patients getting their first refill. And over the course of the first year, approximately 83% of patients who started Dupixent remained on therapy.

現在來看看 Dupixent，根據我們的合作夥伴賽諾菲統計，2018 年第一季全球淨銷售額為 1.31 億美元，其中美國淨銷售額為 1.17 億美元。潛在需求依然強勁，處方總量和接受治療的患者人數較上一季較上一季較上季成長約 25%。本季每週新增患者超過 500 人。此外，我們始終看到較高的續藥率，超過 90% 的患者都能獲得首次續藥。在第一年，約有 83% 的 Dupixent 患者堅持接受了治療。

Over 10,000 health care providers have prescribed Dupixent through the first quarter and we're beginning to advance depth of prescribing among users, with nearly half of these HCPs having prescribed Dupixent to 3 or more patients. Dupixent prescribers are highly satisfied, frequently referring to Dupixent as a drug that has been transformational to the lives of their patients and their treatment practice.

第一季已有超過 10,000 名醫療保健提供者開立了 Dupixent 處方，我們開始提高使用者處方的深度，其中近一半的醫療保健提供者已為 3 名或更多患者開立了 Dupixent 處方。Dupixent 的處方醫生非常滿意，他們經常稱 Dupixent 是一種改變了患者生活和治療實踐的藥物。

We have recently commenced airing a national disease state awareness TV advertisement in order to increase awareness of atopic dermatitis and to encourage appropriate patients to seek further treatment. We also plan to launch (technical difficulty) on-air direct to consumer campaign in the second half of the year. We have high expectations for Dupixent and are optimistic about continued growth in the U.S. market in adult atopic dermatitis and multiple planned launches throughout the world in this indication.

我們最近開始播放全國性的疾病狀態意識電視廣告，以提高人們對異位性皮膚炎的認識，並鼓勵合適的患者尋求進一步治療。我們也計劃在今年下半年推出（技術困難）面向消費者的電視廣告宣傳活動。我們對 Dupixent 寄予厚望，並對其在美國成人特應性皮膚炎市場的持續增長以及計劃在全球範圍內針對該適應症的多次上市持樂觀態度。

In addition, we also anticipate meaningful opportunities for Dupixent in adolescent and pediatric atopic dermatitis, in adult and pediatric asthma and in other indications, such as nasal polyps and eosinophilic esophagitis.

此外，我們也預期 Dupixent 在青少年和兒童異位性皮膚炎、成人和兒童氣喘以及其他適應症（如鼻息肉和嗜酸性食道炎）方面具有重要的應用前景。

U.S. Dupixent net sales in the first quarter were impacted by trade inventory movements and to a lesser extent high patient assistance program cost, which are typical in the beginning of the year for specialty care products. We believe that a much better metric for assessing the launch and product potential at this point is to look at the total growth of prescriptions and the increase in new patients added, both of which were increased by 25% sequentially quarter-over-quarter and the high persistence rates.

第一季美國Dupixent淨銷售額受到貿易庫存變動的影響，其次是較高的病患援助計畫成本，這在年初對於特殊護理產品來說很常見。我們認為，目前評估產品上市和潛力的更佳指標是查看處方總量的增長和新增患者的增加，這兩項指標均環比增長了 25%，並且患者持續率很高。

As you heard from both Len and George, we've completed a regulatory submission for Dupixent in the asthma indication with our anticipated FDA PDUFA date in October 2018. We along with our collaborator, Sanofi, are preparing for an anticipated launch in this indication later this year.

正如您從 Len 和 George 那裡聽到的，我們已經完成了 Dupixent 用於治療氣喘的監管申請，預計 FDA PDUFA 日期為 2018 年 10 月。我們與合作夥伴賽諾菲正在為今年稍後在該適應症中推出產品做準備。

Turning to Praluent. Global net sales in the first quarter, as recorded by our collaborator, Sanofi, was $60 million. We're very pleased with the positive data from the cardiovascular outcome study. We've continued to work with payers to implement our new commercial strategy, and just earlier this week, we announced a payer agreement in which Praluent was selected as the exclusive PCSK9 inhibitor on the Express Scripts' National Preferred Formulary.

轉向Praluent。根據我們的合作夥伴賽諾菲統計，第一季全球淨銷售額為 6,000 萬美元。我們對心血管結果研究的正面數據感到非常滿意。我們一直與支付方合作，實施我們的新商業策略。就在本週早些時候，我們宣布了一項支付方協議，Praluent 被選為 Express Scripts 國家優選處方集中的獨家 PCSK9 抑制劑。

Regeneron and Sanofi have agreed to significantly reduce the net price of Praluent in return for straightforward access for appropriate patients and easing out-of-pocket cost. We continue to engage productively with several other payers. We plan to make a submission to regulatory authorities by midyear based on the cardiovascular outcomes data.

再生元和賽諾菲已同意大幅降低 Praluent 的淨價，以換取合適的患者能夠更便捷地獲得該藥物，並減輕患者的自付費用。我們繼續與其他幾家支付者進行富有成效的合作。我們計劃在年中之前根據心血管結果數據向監管機構提交一份報告。

Global net sales of Kevzara, as recorded by our collaborator, Sanofi, were $12 million in the first quarter. Kevzara is our IL-6 or antibody for rheumatoid arthritis. Although the RA market is crowded, it represents significant opportunity, and we believe that Kevzara has a well-differentiated product profile, most notably, the improvement in radiographic disease progression.

根據我們的合作夥伴賽諾菲公司記錄，Kevzara 第一季的全球淨銷售額為 1,200 萬美元。Kevzara 是我們用於治療類風濕性關節炎的 IL-6 抗體。儘管 RA 市場競爭激烈，但它代表著巨大的機遇，我們相信 Kevzara 具有差異化的產品特性，最顯著的是，它改善了放射學疾病進展。

We have been working with payers to secure improved access for Kevzara. Simultaneously, we continue to work on driving the breadth and depth of prescribing across all health care providers.

我們一直在與付款方合作，以確保Kevzara能夠得到更好的治療。同時，我們繼續努力擴大和深化所有醫療保健提供者的處方範圍和深度。

In immuno-oncology, our team is moving full speed ahead in preparing for the potential U.S. and EU approvals of our PD-1 antibody cemiplimab as the first treatment for advanced cutaneous squamous cell carcinoma or CSCC. This week, we announced that the FDA accepted for priority review our Biologics License Application for cemiplimab in CSCC with a PDUFA date in October 2018.

在免疫腫瘤學領域，我們的團隊正全力以赴地準備，爭取美國和歐盟批准我們的 PD-1 抗體 cemiplimab 作為治療晚期皮膚鱗狀細胞癌 (CSCC) 的首個療法。本週，我們宣布 FDA 已接受我們用於治療 CSCC 的 cemiplimab 的生物製品許可申請，​​並給予優先審查，PDUFA 日期為 2018 年 10 月。

A regulatory application in this indication has also been accepted by the European Medicines Agency, and we expect a decision in the first half of 2019. In the U.S., we have hired and are training an experienced and specialized field-based team to ensure that we are ready to launch immediately following approval.

此適應症的監管申請也已獲得歐洲藥品管理局的受理，我們預計將在 2019 年上半年收到決定。在美國，我們已經聘請並正在培訓一支經驗豐富且專業的現場團隊，以確保我們在獲得批准後能夠立即啟動專案。

Cemiplimab is a collaboration product with Sanofi, where in the U.S. we'll be taking commercial lead and record sales. In just 3 short years, we've gone from initiating our first immuno-oncology clinical study to potentially having our first immuno-oncology treatment approved. Ultimately, our efforts to advance cemiplimab as quickly as possible come down to the significant unmet need facing patients with advanced CSCC and our commitment to giving them an effective treatment option.

Cemiplimab 是與賽諾菲合作的產品，在美國，我們將佔據商業主導地位並創造銷售記錄。短短 3 年時間，我們就從啟動第一個免疫腫瘤臨床研究，發展到有可能獲得第一個免疫腫瘤療法的批准。歸根究底，我們努力盡快推進 cemiplimab 的研發，是因為晚期 CSCC 患者面臨著巨大的未滿足需求，而我們致力於為他們提供有效的治療選擇。

CSCC is the second most common skin cancer worldwide. It's estimated about 750,000 patients are diagnosed annually in the U.S. The vast majority of these patients somewhere between 96% and 98% are cured by surgery. Even so, this leaves thousands of patients with unmet need. While estimates vary, they suggest that between 4,000 to 8,000 patients die annually. Today, there are no FDA- or EMA-approved treatments for advanced CSCC and these patients currently face a hard and long treatment journey.

皮膚鱗狀細胞癌是全球第二大常見皮膚癌。據估計，美國每年約有 75 萬名患者被診斷出患有此病。其中絕大多數患者（治癒率介於 96% 到 98% 之間）透過手術治癒。即便如此，仍有成千上萬的患者的需求未被滿足。雖然估計數字各不相同，但有跡象表明，每年有 4,000 至 8,000 名患者死亡。目前，尚無獲得 FDA 或 EMA 批准的晚期 CSCC 的治療方法，這些患者目前面臨著漫長而艱難的治療之路。

We look forward to sharing updated data from both our Phase I and Phase II CSCC clinical studies this June at ASCO. Among the accepted abstracts, are a first look at our proof-of-concept data for cemiplimab in non-small cell lung cancer, and a trial-in-progress poster for our anti-LAG3 candidate REGN3767, which is being studied as both the monotherapy and in combination with cemiplimab.

我們期待在今年六月的ASCO會議上分享我們I期和II期CSCC臨床研究的最新數據。在已接受的摘要中，有我們首次展示 cemiplimab 在非小細胞肺癌中的概念驗證數據，以及我們正在研究的抗 LAG3 候選藥物 REGN3767 的試驗進展海報，該藥物正在作為單藥療法和與 cemiplimab 聯合療法進行研究。

And with that, I turn the call to Bob.

於是，我把電話轉給了鮑伯。

Thanks, Marion, and good morning, everyone. During today's call, I'll discuss our first quarter 2018 financial performance and provide updates to our full year 2018 guidance line items.

謝謝你，瑪麗昂，大家早安。在今天的電話會議上，我將討論我們 2018 年第一季的財務業績，並更新我們 2018 年全年業績指引。

Regeneron's first quarter 2018 EPS of $4.67 per diluted share, on non-GAAP net income of $537 million has established a solid start for the year. These results represent a 60% and 59% year-over-year increase in our non-GAAP diluted EPS and net income, respectively.

Regeneron 2018 年第一季每股攤薄收益為 4.67 美元，非 GAAP 淨收入為 5.37 億美元，為今年奠定了良好的開端。這些結果分別代表我們的非GAAP稀釋後每股盈餘和淨收入年增60%和59%。

As a reminder, Regeneron's first quarter 2018 non-GAAP net income excludes noncash share-based compensation expense, and beginning in this quarter, the changes in fair value of equity investments recognized in accordance with the company's recent adoption of Accounting Standards Update 2016-01.

提醒一下，Regeneron 2018 年第一季的非 GAAP 淨收入不包括非現金股份支付費用，並且從本季度開始，根據公司最近採用的會計準則更新 2016-01 確認了權益投資公允價值的變動。

A full reconciliation of GAAP and non-GAAP earnings is set forth in our earnings release, which can be found on our website.

我們的獲利報告詳細列出了 GAAP 和非 GAAP 收益的調整情況，您可以在我們的網站上找到該報告。

Total revenues grew 15% year-over-year to $1.51 billion, driven by continuing strength in our flagship EYLEA franchise and higher contribution from commercialization of Dupixent. Partially offset by a lower revenue contribution from Sanofi in connection with the discovery and preclinical development agreement that ended on December 31, 2017. EYLEA net product sales in the United States grew 15% to $984 million compared with $854 million net sales in the first quarter of 2017. U.S. EYLEA distributor inventory experienced a modest increase as compared to the fourth quarter of 2017, yet remained within our normal 1- to 2-week targeted range.

總營收年增 15% 至 15.1 億美元，這主要得益於我們旗艦產品 EYLEA 的持續強勁表現以及 Dupixent 商業化帶來的更高貢獻。部分被賽諾菲因 2017 年 12 月 31 日終止的發現和臨床前開發協議而帶來的收入貢獻減少所抵消。EYLEA 在美國的淨產品銷售額成長了 15%，達到 9.84 億美元，而 2017 年第一季的淨銷售額為 8.54 億美元。與 2017 年第四季相比，美國 EYLEA 經銷商的庫存略有增加，但仍在我們正常的 1 至 2 週的目標範圍內。

Additionally, U.S. EYLEA's gross to net percentage increased compared to first quarter 2017 due to slightly higher rebate provisions for government and commercial programs.

此外，由於政府和商業項目的退款規定略有提高，美國安樂死的毛利淨利比與 2017 年第一季相比有所增長。

Ex U.S. EYLEA net product sales, which are recorded by our collaborator Bayer, were $624 million for the 3 months ended March 31, 2018, representing an 18% operational and 29% reported increase on a year-over-year basis.

除美國以外，EYLEA 淨產品銷售額（由我們的合作夥伴拜耳記錄）在截至 2018 年 3 月 31 日的三個月內為 6.24 億美元，年增 18%（按營運計算）和 29%（按報告計算）。

In the first quarter of 2018, Regeneron recognized $232 million from our share of net profits from EYLEA sales outside the U.S. compared to $175 million in the first quarter of 2017. Total Bayer collaboration revenue was $248 million in the first quarter of 2018 as compared to $194 million in the first quarter of 2017. Total Sanofi collaboration revenue was $189 million for the first quarter of 2018 compared with $210 million for the first quarter of 2017. The Sanofi collaboration revenue line item primarily consists of reimbursement of Regeneron incurred R&D expenses, reimbursement of Regeneron incurred commercialization related expenses and the recognition of the deferred revenue from the immuno-oncology upfront payments, partly offset by our share of losses in connection with the commercialization of antibodies. A significant driver of the year-over-year decrease in Sanofi collaboration revenue was the 2017 expiration of the discovery and preclinical development agreement.

2018 年第一季度，Regeneron 從美國以外地區 EYLEA 的銷售淨利潤中確認了 2.32 億美元的收入，而 2017 年第一季為 1.75 億美元。2018 年第一季拜耳合作總營收為 2.48 億美元，而 2017 年第一季為 1.94 億美元。2018 年第一季度，賽諾菲合作總收入為 1.89 億美元，而 2017 年第一季為 2.1 億美元。賽諾菲合作收入項目主要包括：報銷 Regeneron 發生的研發費用、報銷 Regeneron 發生的商業化相關費用以及確認免疫腫瘤預付款的遞延收入，部分被我們應承擔的抗體商業化相關損失所抵消。導致賽諾菲合作收入年減的一個重要原因是 2017 年發現和臨床前開發協議到期。

We recorded $48 million of revenue in the first quarter of 2017 related to reimbursements of our R&D expenses from this agreement as compared to no revenue this quarter. Offsetting this revenue decrease was higher Sanofi R&D reimbursement revenue associated with our increased investment in immuno-oncology and a decrease in our share of losses in connection with a commercialization of Dupixent, Praluent and Kevzara, which were $75 million loss in the first quarter of 2018 as compared to a loss of $108 million in the first quarter of 2017. The lower share of loss was primarily attributable to Dupixent's first quarter 2018 sales in comparison to no sales in the first quarter of 2017, given the late March 2017 U.S. launch.

2017 年第一季度，我們因該協議而獲得了 4,800 萬美元的研發費用報銷收入，而本季則沒有收入。抵銷這一收入下降的是，由於我們在免疫腫瘤學領域的投資增加，賽諾菲研發報銷收入增加；此外，由於 Dupixent、Praluent 和 Kevzara 的商業化，我們承擔的虧損份額減少，2018 年第一季虧損 7,500 萬美元，而 2017 年第一季虧損 1.08 億美元。虧損份額降低主要歸因於 Dupixent 在 2018 年第一季的銷售額，而 2017 年第一季則沒有銷售額，因為該產品於 2017 年 3 月下旬才在美國上市。

Global sales of Dupixent, Praluent and Kevzara as recorded by our collaborator Sanofi for the first quarter of 2018, were Dupixent $131 million, Praluent $60 million and Kevzara $12 million. The split of U.S. and rest of the world net sales for these collaboration products is set out in our press release.

根據我們的合作夥伴賽諾菲的記錄，2018 年第一季 Dupixent、Praluent 和 Kevzara 的全球銷售額分別為：Dupixent 1.31 億美元，Praluent 6000 萬美元，Kevzara 1200 萬美元。這些合作產品的美國市場和世界其他地區的淨銷售額佔比已在我們的新聞稿中列出。

In the first quarter of 2018, other revenue was $86 million versus $56 million during the first quarter of 2017. This increase was primarily due to reimbursements from our collaborator, Teva, for the continued development of fasinumab, our NGF antibody, in the recognition of deferred revenue associated with this program from Teva and Mitsubishi Tanabe Pharma. As a reminder, you can find a summary of the components of other revenue in the MD&A section of our 10-Q.

2018 年第一季其他收入為 8,600 萬美元，而 2017 年第一季為 5,600 萬美元。這一成長主要是由於我們的合作方梯瓦製藥公司（Teva）對我們繼續開發 NGF 抗體 fasinumab 的補償，以確認梯瓦製藥公司和三菱田邊製藥公司與該專案相關的遞延收入。提醒一下，您可以在我們 10-Q 表格的 MD&A 部分找到其他收入組成部分的摘要。

Turning now to expenses. Non-GAAP R&D expenses were $458 million for the first quarter of 2018 as compared to $434 million for the first quarter of 2017. The increase in non-GAAP R&D expense was the result of the continued late-stage clinical development for cemiplimab and fasinumab programs offset by lower clinical manufacturing costs.

接下來談談費用。2018 年第一季非 GAAP 研發費用為 4.58 億美元，而 2017 年第一季為 4.34 億美元。非GAAP研發費用的增加是由於cemiplimab和fasinumab計畫持續的後期臨床開發，但被較低的臨床生產成本所抵消。

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 $278 million for the 3 months ended March 31, 2018, compared to $188 million for the 3 months ended March 31, 2017. This increase was primarily driven by the expiration of the discovery and preclinical development agreement at the end of 2017, resulting in lower reimbursements received from Sanofi during the first quarter of 2018, offset by higher reimbursements received from our collaborators for cemiplimab and fasinumab. Our press release includes the information required to calculate unreimbursed non-GAAP R&D expense. We are tightening our full year 2018 guidance for non-GAAP unreimbursed R&D expense to be $1.23 billion to $1.31 billion from our previous guidance of $1.23 billion to $1.33 billion.

截至 2018 年 3 月 31 日止的三個月，我們的非 GAAP 未報銷研發費用（計算方法為非 GAAP 研發總費用減去合作方的研發報銷）為 2.78 億美元，截至 2017 年 3 月 31 日止的三個月為 1.88 億美元。這一增長主要是由於 2017 年底發現和臨床前開發協議到期，導致 2018 年第一季從賽諾菲收到的報銷款項減少，但被我們從合作方收到的 cemiplimab 和 fasinumab 的較高報銷款項所抵消。我們的新聞稿包含了計算未報銷的非GAAP研發費用所需的資訊。我們將 2018 年全年非 GAAP 未報銷研發費用的預期從先前的 12.3 億美元至 13.3 億美元下調至 12.3 億美元至 13.1 億美元。

Next, non-GAAP SG&A expense was $296 million for the first quarter of 2018 as compared to $243 million for the 3 months ended March 31, 2017. As noted in our February 28 earnings call, we originally guided to higher SG&A this year compared to 2017 due to the ongoing launches in Dupixent and Kevzara, an increase in EYLEA commercialization expense, with an increased focus on diabetic eye disease as well as commercialization expenses for the anticipated 2018 U.S. approvals for cemiplimab in CSCC and dupilumab for asthma.

其次，2018 年第一季的非 GAAP 銷售、一般及行政費用為 2.96 億美元，截至 2017 年 3 月 31 日的三個月為 2.43 億美元。正如我們在 2 月 28 日的財報電話會議上所指出的，由於 Dupixent 和 Kevzara 的持續上市、EYLEA 商業化費用的增加（更加關注糖尿病眼病）以及預計 2018 年 cemiplimab（用於治療 CSCC）和 dupilumab（用於治療哮喘）在美國獲得批准的商業化費用，我們預計將高於 207 年。

Although we still expect higher non-GAAP SG&A in comparison to full year 2017 for the reasons explained above, due to lower first quarter 2018 G&A and Praluent commercial expenses and lower forecasted SG&A spend in the second half of the year, Regeneron is tightening and lowering our full year 2018 non-GAAP SG&A expense to be $1.325 billion to $1.395 billion from our previous guidance range of $1.35 billion to $1.45 billion.

儘管由於上述原因，我們仍然預計 2018 年全年非 GAAP SG&A 費用將高於 2017 年全年，但由於 2018 年第一季 G&A 費用和 Praluent 商業支出減少，以及下半年 SG&A 支出預計減少，Regeneron 正在收緊並下調 2018 年全年非 GAAP SG&A 13.億美元下調至 13.25 億美元至 13.95 億美元。

Sanofi reimbursement of Regeneron commercialization related expenses, a line item found within Sanofi collaboration revenue was $87 million for the first quarter of 2018. We are tightening our full year 2018 guidance for reimbursement of Regeneron commercialization-related expenses to be $450 million to $485 million from our previous guidance of $450 million to $500 million.

2018 年第一季度，賽諾菲向 Regeneron 支付的商業化相關費用（該費用包含在賽諾菲合作收入中）為 8,700 萬美元。我們將 2018 年全年與 Regeneron 商業化相關的費用報銷預期從先前的 4.5 億美元至 5 億美元下調至 4.5 億美元至 4.85 億美元。

Turning now to taxes. Our effective tax rate in the first quarter of 2018 was 18% compared to 42% for the first quarter of 2017. The difference was primarily driven by the enactment of the Tax Cuts and Jobs Act, which lowered the U.S. corporate tax rate as well as improved results from our international operations as compared to the first quarter of 2017.

接下來談談稅務問題。2018 年第一季我們的實際稅率為 18%，而 2017 年第一季的實際稅率為 42%。這一差異主要是由於《減稅與就業法案》的頒布，該法案降低了美國企業稅率，並且與 2017 年第一季相比，我們國際業務的業績也有所改善。

As we continue to assess the full impact of the Tax Cuts and Jobs Act and await additional regulatory guidance, we now expect our full year 2018 effective tax rate to be 15% to 18% versus our previous guidance of 15% to 19%. Our first quarter 2018 effective tax rate was lower than the new U.S. federal statutory rate of 21%, due to the new foreign-derived intangible income deduction and the federal tax credit for research activities. Over the next few years, we would expect Regeneron's effective tax rate to stay consistent with 2018 guidance in the mid- to high teens.

在我們繼續評估《減稅與就業法案》的全面影響並等待進一步監管指導的同時，我們現在預計 2018 年全年實際稅率為 15% 至 18%，而我們先前的指導為 15% 至 19%。由於新的外國衍生無形收入扣除和聯邦研發活動稅收抵免，我們 2018 年第一季的實際稅率低於 21% 的美國聯邦法定新稅率。未來幾年，我們預計 Regeneron 的有效稅率將與 2018 年的預期保持一致，保持在十幾到二十幾的水平。

Future regulatory guidance under the Tax Cut and Jobs Act in variability of deductions for stock-based compensation could impact our future effective tax rate.

《減稅與就業法案》未來對股票選擇權激勵扣除額變化的監管指導可能會影響我們未來的實際稅率。

Now to cash flow and the balance sheet. Regeneron ended the quarter of 2018 with cash and marketable securities of $3.4 billion and generated free cash flow in excess of $500 million. Our capital expenditures for the 3 months ended March 31, 2018, were $79 million. As a result of first quarter's spend levels and a revised full year forecast, we are tightening our full year 2018 capital expenditure guidance to be $420 million to $480 million from our prior range of $420 million to $500 million.

接下來我們來看現金流量表和資產負債表。截至 2018 年 2 月 31 日，Regeneron 公司持有現金及有價證券 34 億美元，並產生超過 5 億美元的自由現金流。截至 2018 年 3 月 31 日的三個月內，我們的資本支出為 7,900 萬美元。由於第一季的支出水準和修訂後的全年預測，我們將 2018 年全年資本支出指引範圍從先前的 4.2 億美元至 5 億美元收緊至 4.2 億美元至 4.8 億美元。

Significant 2018 capital projects include the expansion of our manufacturing facilities at Rensselaer, New York, and Limerick, Ireland as well as continued renovations and expansion of our laboratory space within our Tarrytown, New York facility.

2018 年的重大資本項目包括擴大我們在紐約州倫斯勒和愛爾蘭利默里克的製造設施，以及繼續翻新和擴大我們在紐約州塔里敦工廠內的實驗室空間。

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

那麼，我現在想把電話轉回給瑪妮莎。

Thank you, Bob. Operator, this concludes the prepared remarks portion of our call today. We would now like to open the call for Q&A.

謝謝你，鮑伯。接線員，我們今天電話會議的預先準備好的發言部分到此結束。現在我們開始問答環節。

(Operator Instructions) And first we have Ying Huang from Bank of America Merrill Lynch.

（操作說明）首先我們請到的是美國銀行美林證券的黃穎。

So maybe Len and George, since you elaborated more about the PD-1 plans, given the recent data from Merck's KEYTRUDA and Bristol's OPDIVO in first-line non-small cell lung cancer, how do you think your molecules would behave? Is it because you are designing the molecule in such a way that it is going to be more potent even than both? Or are you trying to explore a better combination strategy for PD-1? And then quick one on fasinumab. Can you just elaborate a little more what causes the high dose to be dropped? [Is it also the same study that we see], which is osteonecrosis?

那麼，Len 和 George，既然你們詳細闡述了 PD-1 計劃，鑑於默克公司的 KEYTRUDA 和百時美施貴寶公司的 OPDIVO 在一線非小細胞肺癌治療中的最新數據，你們認為你們的分子會如何表現呢？是因為你設計的分子比它們兩個都更有效嗎？還是您正在探索更好的PD-1合併治療策略？然後快速講一下法西單抗。能否再詳細解釋是什麼原因導致高劑量下降？[我們看到的也是同一項研究嗎？ ]，即骨壞死？

George?

喬治？

Yes, this is George. Thanks for the question. I think that as we try to line up, it is really pretty sobering that despite all the excitement and advances with PD-1 and PD-L1, right now the most important setting and indication where they seem to be active in terms of the number of patients, which is first-line lung cancer. As we all know, the data from the PD-L1s has been quite disappointing. And even with OPDIVO, if you actually look at the data, it, by far, fails to meet the bar of KEYTRUDA. So right now, unbelievably enough, there is only one, in our opinion, clear leader in the first-line lung cancer space. And what we try to explain is that we've designed a series of studies, which will test whether our molecule is in that class, is in the class of KEYTRUDA. We do believe, as you said, that we have a great technology that has succeeded in the past in delivering some of the first and best-in-class molecules, this VelocImmune technology. And on top of that, as we've already described, we have this very impressive and comforting data in the squamous cell carcinoma indication, which has some of the best data ever described in solid tumor settings for a PD-1 agent. So these combine to give us a lot of hope that our first-line cancer studies are going to deliver on the order of KEYTRUDA-like data, which would make us basically a real major competitor in this space. So we are very excited about the opportunity, and we're very hopeful that the molecule in the studies will come through. In terms of your second question about fasinumab, as you already pointed out, there is a -- this is a high-risk, high-reward program, as we've described in the past. It's pretty well demonstrated that the molecule has activity, but it also has certain side effects. It's not osteonecrosis, it's more defined as rapid progression of the osteoarthritis in some patients. And this is something that obviously has been seen with this class and with our molecule before. And so what the Independent Data Monitoring Committee did was, they obviously took an analysis to look at the benefit and the risk that is the therapeutic benefit compared to their analysis of the risk coming from these rapidly progressive osteoarthritis events, and they decided that we should terminate the upper 2 doses and continue with the 2 lower doses. And so we are planning to modify the studies consistent with their recommendations.

是的，這是喬治。謝謝你的提問。我認為，當我們努力進行對比時，儘管 PD-1 和 PD-L1 帶來了令人興奮的進展，但就患者數量而言，目前它們似乎最活躍的領域和適應症是肺癌一線治療，這確實令人清醒。眾所周知，PD-L1 的數據相當令人失望。即使使用 OPDIVO，如果你仔細查看數據，它也遠遠達不到 KEYTRUDA 的標準。所以，令人難以置信的是，目前在我們看來，第一線肺癌治療領域只有一個明顯的領導者。我們試圖解釋的是，我們設計了一系列研究，這些研究將檢驗我們的分子是否屬於該類，是否屬於 KEYTRUDA 類。正如您所說，我們相信我們擁有一項偉大的技術，這項技術過去曾成功地交付了一些首創且一流的分子，這就是 VelocImmune 技術。此外，正如我們已經描述的那樣，我們在鱗狀細胞癌適應症方面獲得了非常令人印象深刻和令人欣慰的數據，這是 PD-1 藥物在實體瘤治療領域中描述過的最佳數據之一。因此，這些因素結合起來讓我們充滿希望，相信我們的第一線癌症研究將取得與 KEYTRUDA 類似的成果，這將使我們成為該領域真正的主要競爭者。因此，我們對這個機會感到非常興奮，並且非常希望研究中的分子能夠成功。關於你提出的第二個問題，即法西單抗，正如你已經指出的那樣，這是一個高風險、高回報的項目，正如我們過去所描述的那樣。已經相當清楚地證明該分子具有活性，但它也存在一些副作用。它不是骨壞死，更準確地說，是某些患者骨關節炎的快速進展。顯然，這種現像以前在這個班級和我們的分子中都出現過。因此，獨立數據監測委員會顯然進行了一項分析，比較了治療獲益和風險，即治療獲益與快速進展性骨關節炎事件帶來的風險，並決定停止使用較高劑量的兩種藥物，繼續使用較低劑量的兩種藥物。因此，我們計劃根據他們的建議修改研究方案。

I just wanted to add, Ying, that -- I think George said it and I said it, but it's worth saying again is that the potential for combinations with PD-1, based upon bispecifics that you are aware of as well as new class of bispecifics that we'll talk to about later this year in our proprietary models, is pretty exciting for us. So it's not only the monotherapy, although clearly the monotherapy is a huge opportunity as evidenced by the $12 billion run rate, the majority of which is a single immuno-oncology agent with or without chemotherapy in lung cancer.

我只想補充一點，英，我想喬治說過，我也說過，但值得再說一遍，那就是基於你所了解的雙特異性抗體以及我們將在今年晚些時候在我們的專有模型中討論的新型雙特異性抗體，與 PD-1 結合的潛力對我們來說非常令人興奮。所以不僅僅是單藥療法，儘管單藥療法顯然是一個巨大的機會，120億美元的年化收入證明了這一點，其中大部分是肺癌的單一免疫腫瘤藥物，無論是否聯合化療。

Right. And when we use the term monotherapy, we should sort of -- we're almost bundling monotherapy and traditional therapies like chemotherapy. Because as we describe, many of our studies are in combination with existing therapies. And as Len said, we also have these new combination approaches that we're excited about.

正確的。當我們使用「單一療法」這個術語時，我們應該——我們幾乎是將單一療法和化療等傳統療法捆綁在一起。因為正如我們所描述的，我們的許多研究都是與現有療法結合的。正如 Len 所說，我們也有一些新的組合方法，我們對此感到非常興奮。

Next, we have Carter Gould from UBS.

接下來，我們請到了瑞銀集團的卡特古爾德。

Obviously, a lot of focus on Dupixent after your partner reported last week. Can you maybe just give a little bit more detail on the commercial dynamics you're seeing, namely persistence on therapy? And I guess, for Marion, whether -- how we should be thinking about IMS data as being predictive of the trends you're seeing in the market landscape?

顯然，在你伴侶上週報告病情後，Dupixent 引起了廣泛關注。您能否更詳細地介紹您觀察到的商業動態，特別是治療的持續性？我想，對於 Marion 來說，我們應該如何看待 IMS 數據，才能預測您在市場格局中看到的趨勢？

I'll let Marion answer that question, but we don't get as bogged down as you do in trying to predict the exact quarter sales. We're looking at the metrics, as Marion said, is how is the launch going. And I'll let Marion reinforce her earlier comments.

我會讓瑪莉安來回答這個問題，但我們不會像你們那樣糾結於預測確切的季度銷售額。正如馬里恩所說，我們正在關注各項指標，看看產品發布進度如何。我再引用瑪莉安之前的評論。

Sure. Let me take, Carter, the persistence question first. And as I mentioned in 2 pieces, both very, very encouraging signs on persistence. First is that we see patients 90% of the time get refills after their first script. So that was one metric that I gave. The second one I gave was looking over a longer period of time of persistence and that was, over the course of time since launch, patients on therapy over that duration at 83%. So 2 metrics, both quite encouraging. I think the other comment is you're talking about some of the other data metrics that we would say is that, what we're seeing in terms of demand and performance on the product, is -- including the NBRx profile, is very consistent with our long-term growth projections for Dupixent. So we are on pace as I mentioned with the NBRx number or new patient scripts on a weekly basis at about 500 per week through the quarter, that's 2,000 new patients a month getting their prescriptions filled for Dupixent, and we see that as a very strong growth signal. Certainly, we're going to work to continue to advance performance but we see that demand going very well at this stage.

當然。卡特，讓我先回答關於堅持不懈的問題。正如我在兩篇文章中提到的，這都是堅持不懈的非常非常令人鼓舞的跡象。首先，我們發現90%的患者在第一次開處方後都會再次開處方。這是我給的一個衡量標準。我給出的第二個結果是著眼於更長的持續時間，即自上市以來，接受治療的患者中有 83% 的人持續接受治療。所以，這兩項指標都相當令人鼓舞。我認為另一個評論是，你談到了一些其他的數據指標，我們想說的是，就產品需求和性能而言，包括 NBRx 指標在內，我們看到的情況與我們對 Dupixent 的長期成長預測非常一致。正如我之前提到的，我們目前每週的新患者處方數量（NBRx）約為 500 張，這意味著本季度每月有 2000 名新患者獲得 Dupixent 處方，我們認為這是一個非常強勁的增長信號。當然，我們會持續努力提升產品效能，但目前來看，市場需求表現非常良好。

And we should just reinforce that once you just try to look across other agents at what the persistent rates are over the course of the year, these numbers are really quite impressive and speak to the need and how satisfied patients are with the treatment.

我們應該強調的是，只要你看看其他藥物在一年中的持續療效，這些數字就非常驚人，也說明了市場需求以及患者對治療的滿意度。

We have Terence Flynn from Goldman Sachs.

我們請到了高盛的特倫斯·弗林。

Maybe as we think about your immuno-oncology strategy, when might we see some initial combo data? And really is the big push here on the bispecifics? Or are you looking at other approaches as well? And then the second part of that is, you guys have had a somewhat disruptive approach to pricing of your drugs. Is that how we should think about cemiplimab as well?

當我們考慮您的免疫腫瘤學策略時，我們什麼時候才能看到一些初步的聯合治療數據？而目前的主要動力真的在於雙特異性抗體嗎？或者您還在考慮其他方法嗎？其次，你們在藥品定價方面採取了頗具顛覆性的做法。我們是否也應該這樣看待cemiplimab？

Well, maybe George will take the first part and then Len will take the second part. But -- so this is George. We're obviously very excited about this sort of dual opportunity of cemiplimab and of our bispecifics both individually and in combination. But as you also just pointed out, with cemiplimab, we have just with that a sort of dual approach of combining with a series of more traditional agents, as I described, traditional chemotherapeutic agents. Other checkpoint inhibitors including others and our own as well as things, for example, that we're collaborating with other people, such as certain types of vaccines and so forth. So that's one whole set of combination opportunities with cemiplimab. We have the bispecifics, which by themselves can be used individually or with existing therapies but also combinations with the cemiplimab, and we -- I think have already announced that we have already started dosing patients with our first bispecific and PD-1 in combination. And we hope that we'll be seeing data and be reporting on that as well. But the very exciting aspect of this for us is every one of our bispecifics can be evaluated individually, but also we believe in combination with cemiplimab and other checkpoint inhibitors as well as with other agents and as well as with this new class of bispecifics that Len mentioned we will be disclosing over the course of the year.

或許喬治會出演第一部分，然後倫會出演第二部分。但是——這就是喬治。我們顯然對 cemiplimab 和我們的雙特異性抗體單獨或合併使用所帶來的這種雙重機會感到非常興奮。但正如您剛才指出的那樣，對於西米普利單抗，我們採取了一種雙重方法，即與一系列更傳統的藥物（如我所描述的傳統化療藥物）相結合。其他檢查點抑制劑，包括我們自己的和其他人研發的，以及我們正在與其他人合作研發的，例如某些類型的疫苗等等。所以這就是 cemiplimab 的一整套合併用藥方案。我們有雙特異性抗體，它們本身可以單獨使用，也可以與現有療法一起使用，也可以與 cemiplimab 聯合使用。而且，我認為我們已經宣布，我們已經開始使用我們的第一種雙特異性抗體和 PD-1 聯合療法給患者用藥。我們希望能夠獲得相關數據，並對此進行報告。但對我們來說，最令人興奮的是，我們每一種雙特異性抗體都可以單獨進行評估，而且我們相信，它們還可以與 cemiplimab 和其他檢查點抑製劑以及其他藥物，以及 Len 提到的我們將在今年內公佈的這一類新型雙特異性抗體聯合使用。

And in terms of price, Terence, obviously -- and if you're thinking about trying a model our opportunity both in CSCC and how we will compete elsewhere, first of all, I might just say in CSCC, you have to think about the fact that there is a reasonable size patient populations, although it's hard to know because there hasn't been an approved treatment for advanced disease. And also, you should go back and look at our data. We can remind you later that we have very long duration of therapy, and many patients are still on drug as of the last update. So that plays. In terms of the actual price, we like to price towards value. These are, I think, high-value molecules to patients. And we'll let you know what we come out with when we do.

至於價格方面，特倫斯，顯然——如果你正在考慮嘗試一種模式，看看我們在 CSCC 領域的機會以及我們將如何在其他領域競爭，首先，我只想說，在 CSCC 領域，你必須考慮到患者群體規模相當可觀，儘管很難知道，因為還沒有針對晚期疾病的獲批療法。另外，您也應該回去查看一下我們的數據。我們稍後會提醒您，我們的治療療程非常長，截至上次更新，許多患者仍在接受藥物治療。就這樣播放了。就實際價格而言，我們傾向於以價值為導向定價。我認為這些分子對患者來說非常有價值。等我們有了結果，會第一時間通知你們。

We have Geoffrey Porges from Leerink Partners.

我們邀請到了來自 Leerink Partners 的 Geoffrey Porges。

Len, the question is, could you address some of what (inaudible) of Regeneron? Things like no long-term guidance, no buybacks or dividends, no price increases, no product acquisitions. Given the fact that the company has lost more than 40% of its value over the last year, are you and the board reconsidering any of these sacred cows?

Len，問題是，可以談談 Regeneron 的一些（聽不清楚）狀況嗎？例如，不提供長期業績指引，不進行股票回購或分紅，不漲價，不進行產品收購。鑑於該公司在過去一年中市值縮水超過 40%，您和董事會是否正在重新考慮這些不可動搖的原則？

So let's take them one-by-one. I'm not sure -- I got to write them down. You said product acquisitions, what else did you say, Geoff?

那我們就逐一來看。我不太確定——我得把它們寫下來。你說的是產品收購，你還說了什麼，傑夫？

Price increases, buyback or dividends, long-term guidance.

價格上漲、回購或分紅、長期業績指引。

Slowdown, slowdown. I can't write that fast. Price increases, buybacks, go ahead.

慢點，慢點。我寫不了那麼快。提價、回購，統統都行。

Buybacks or dividends, long-term guidance.

股票回購或分紅，長期業績指引。

Guidance. Okay. So let's go -- let's take the easy ones. We have 6 approved drugs and 17 in the clinic. We have, what I think of as one of the most prolific R&D engines in the industry, and we are not nearly as desperate as other companies are to fill up gaps in the pipeline. So it would be sort of senseless for us to compete in the market where people are dramatically overpaying, and we have a tremendous pipeline of our own. It doesn't mean we don't want to work with other companies. You're going to hear more opportunities for us to leverage the capabilities that we do with what other companies can do in some very exciting spaces we're working on. But in terms of just going out and buying a Phase III molecule that treats Parkinson's disease, buy some small molecule mechanism that would just make no sense for us.

指導。好的。那麼，我們開始吧——我們先選簡單的。我們有 6 種核准藥物，臨床上使用的藥物有 17 種。我認為我們擁有業內最高效的研發引擎之一，但我們並不像其他公司那樣迫切需要填補產品線中的空白。因此，如果我們參與到人們支付過高價格的市場競爭中，那就有點毫無意義了，而且我們自己也有龐大的產品線。但這並不意味著我們不想與其他公司合作。你們將會聽到更多機會，讓我們能夠利用自身能力，結合其他公司在一些我們正在努力開拓的令人興奮的領域中的能力。但就直接去買一種用於治療帕金森氏症的 III 期分子藥物，或購買一些小分子藥物而言，這對我們來說毫無意義。

And I think as Len mentioned, Intellia and Alnylam are very interesting examples, where we are, as Len said, leveraging our internal research capabilities with something that somebody else brings to the table, which we believe is very synergistic.

正如 Len 所提到的，我認為 Intellia 和 Alnylam 就是非常有趣的例子，正如 Len 所說，我們正在利用我們內部的研究能力，結合其他人帶來的東西，我們認為這會產生非常強的協同效應。

In terms of guidance, we try and give guidance where the knowledge is asymmetric. But we don't think, Geoff, to be frank, it's our job to try and guess things that we don't have any more information about than you guys have. And we also don't want to spend a lot of the -- of our internal team's intellectual horsepower trying to guess what a given number of patients will be. That's kind of why you guys are overpaid. You are supposed to make those guesses. So we don't have -- Bob gives a lot of guidance on things that you don't have information about, and then there was a ton of it in there, but to give you product guidance and make guesses, I don't know, we don't want to get in that game because that's not what really the game that the board is in or the company. In terms of price increases, this is not an environment where you can take price increases easily. We have felt that growing by price increases is not our strategy. We drive the growth by fundamental increase in the penetration or diversity of patients that can be on our approved drugs or bring new drugs to market, taking small price increases consistent with inflation or medical inflation is perfectly reasonable. But we don't want to be participating in the undoing of the industry where there's so much enmity towards us and there's so much potential for bad government action. Egregious price increases are not a strategy we think are worth deploying. In terms of capital allocation, I can assure you that the financial team and the board looks at this on a regular basis. We're well aware of all the data. We are data-driven. We know what you can do with dividends with buybacks, with acquisitions, with bolt-on acquisitions, with internal discovery, with partner discovery, keeping money in the bank. We've got them all, and we study them all. And I think we'll tell you about them as our strategy does or does not [involve]. I think that covers your list, Geoff.

在指導方面，我們會努力在知識不對稱的情況下提供指導。但坦白說，傑夫，我們認為，猜測那些我們並不比你們掌握更多資訊的事情，並不是我們的職責。而且我們也不想浪費我們內部團隊的大量智力資源去猜測會有多少病人。這就是你們薪水過高的原因之一。這些猜測應該是你自己做出的。所以我們沒有——鮑勃會就你不了解的事情提供很多指導，而且這方面的內容非常多，但是要給你產品指導和做出猜測，我不知道，我們不想涉足這個領域，因為那並不是董事會或公司真正關注的重點。就價格上漲而言，這不是一個可以輕易提價的環境。我們一直認為，透過漲價來實現成長並不是我們的發展策略。我們透過提高已獲批准藥物的患者群體的滲透率或多樣性，或將新藥推向市場，來推動成長。因此，根據通貨膨脹或醫療通膨情況進行小幅提價是完全合理的。但我們不想參與這個產業的衰退中，因為那裡對我們充滿敵意，而且政府很可能會採取不良行動。我們認為，大幅漲價並非值得採取的策略。關於資本配置方面，我可以向你保證，財務團隊和董事會都會定期審視這個問題。我們對所有數據都非常清楚。我們以數據為導向。我們知道您可以如何利用股息進行股票回購、收購、補充收購、內部開發、合作夥伴開發，從而將資金留在銀行。我們擁有所有這些資料，並且我們研究所有這些資料。我認為我們會根據我們的策略是否涉及這些內容來告訴你們。我想這就是你需要列出的清單了，傑夫。

We have Matthew Harrison from Morgan Stanley.

我們請到了摩根士丹利的馬修·哈里森。

I guess if I could just ask a couple of the underlying trends on EYLEA for the quarter. You talked about DME growth, again, I mean -- can you just describe how you see that market growing? And if that market's growing faster or slower than the AMD market still? And then just talk a little bit about, I mean, in past first quarters, you've seen some underlying dynamics either from patients finding it harder to get to the doctor or things like that due to weather? Maybe you could just describe if there are any of those issues in the quarter?

我想問一下關於安永本季的一些基本趨勢。您剛才又談到了DME（耐用醫療設備）市場的成長，我的意思是—您能描述一下您認為這個市場將如何成長嗎？如果這個市場的成長速度仍然比AMD市場快或慢呢？然後，請您稍微談談，在過去的第一個季度中，您是否觀察到一些潛在的動態，例如由於天氣等原因，患者就醫更加困難？您能否描述本季是否有這些問題？

It's always hard to know. We had a good quarter with EYLEA, despite the fact that there was some transient concern about intraocular inflammation, which based on our monitoring now has returned to background levels, and we don't seem to have had any significant impact on the business there, which we are pleased with. The product grew year-over-year. I don't think we've really yet made the big push in diabetes because we have a good approval for DME and that patients do kind of get to the doctor, although there are a lot that don't. But we're looking to get the broader indication for diabetic retinopathy, and then in concert with that have a much bigger push to get patients to the doctor, hopefully, to have their diabetic eye disease treated. We do see -- so we haven't seen a big growth yet in diabetes, but we still see it. I should emphasize that -- while I said that AMD is well penetrated, it's still growing by demographics. And we're seeing an overall growth in the AMD market because more and more people are living longer, and so there are more and more people getting age-related macular degeneration. Okay?

這總是很難知道。儘管我們曾短暫擔憂眼內炎症，但愛樂（EYLEA）本季表現良好。根據我們的監測，眼內發炎現已恢復到正常水平，而且似乎並未對該公司的業務造成任何重大影響，對此我們感到滿意。該產品銷量較去年同期成長。我認為我們還沒有真正大力推進糖尿病治療，因為我們對糖尿病性黃斑水腫（DME）的審批很順利，而且患者通常都能去看醫生，儘管還有很多患者沒有去看醫生。但我們希望擴大糖尿病視網膜病變的適應症範圍，並以此為契機，加強鼓勵患者就醫，希望能治療他們的糖尿病眼疾。我們確實看到了——雖然我們還沒有看到糖尿病病例大幅增長，但我們仍然看到了糖尿病病例的增長。我應該強調一點——雖然我說過 AMD 的市場滲透率很高，但從人口統計數據來看，它仍在增長。我們看到 AMD 市場整體呈現成長趨勢，因為越來越多的人壽命延長，因此患有老年黃斑部病變的人也越來越多。好的？

We have Phil Nadeau from Cowen and Company.

我們邀請到了來自 Cowen and Company 的 Phil Nadeau。

Maybe to follow up on those questions, 2 longer-term questions on EYLEA. The first on non-proliferative diabetic retinopathy. In theory, it's a large market, although our consultants said, it may be hard to get anti-VEGF adoption there. So can you talk about your plans to try and change the standard of care, in particular any patient populations within that larger group that would be most susceptible to anti-VEGF therapy? And then second on the competition you've alluded to in your prepared remarks, we did see some new data from brolucizumab this week. Could you give us your perspectives on that data?

或許可以針對這些問題提出兩個關於EYLEA的長期問題。第一篇關於非增殖性糖尿病視網膜病變的文章。理論上，這是一個很大的市場，儘管我們的顧問表示，在那裡推廣抗 VEGF 療法可能比較困難。那麼，您能否談談您改變現有治療標準的計劃，特別是針對更大群體中哪些患者群體最容易受到抗 VEGF 療法的影響？其次，關於您在準備好的演講稿中提到的競爭，我們本週確實看到了 brolucizumab 的一些新數據。您能否就這些數據談談您的看法？

Yes. So in the diabetic retinopathy, the needle mover from the people we talk to will be not simply or only the important thing of improving the diabetic retinopathy but to prevent the onset of vision-threatening diabetic retinopathy, the vision-threatening complications, the sight threatening. And then we're going to be able to look at those data from a PANORAMA study later this year. But I do think that this is like any other market. I mean, if you go back -- I remember our Chairman, Roy Vagelos, told me that when he launched the first statin, the cardiologist told him, "Well, there is no real need for a statin. We can control all of that with diet and exercise" and that was the prevailing view. So there is work that you have to do to change the practice of medicine based on data. It doesn't happen overnight. It takes really strong data, a really strong commercial effort. We're really excited how Marion has integrated so quickly into the organization, and she has taken that on as something that's really important to us. So we're looking forward over the years to come to have success in that area. There was a recent approval by the FDA by a small company of a untethered device, that is a device that could diagnose diabetic retinopathy and whether or not you should urgently see a retinal specialist merely by -- that could sit in a drugstore, it could sit in your general practice office, it could sit in your ophthalmologist, it could sit with the optometrist and it's been approved. It doesn't need a doctor to administer. You just take a non-dilated picture of the retina and so -- and they found sort of striking data, which the FDA approved the drug on. And I think more to come about how underdiagnosed this condition is when you have a powerfully broad screening. And there are a lot of other efforts just to do the exact same thing, in terms of machine learning or as you call it, artificial intelligence. So we think that -- and when you have a treatment, and we have the broad label, then you can start to push at the front end of the people who could really benefit, and I think there's a lot of them. In terms of the RTH data, didn't see it very much new there. What I heard about was that, I think, it was in the mid-80s percentile of those people who went on to the 12-week data could stay on the 12-week data. But at the end of the day, you can slice this data up any which way you want. You're still getting about 50-odd percent of people who can go to every 12 weeks, and based on -- and they haven't identified people because if you look carefully, the people who don't succeed at 12 weeks are the ones that lost -- I think a significant amount of vision was one of the criteria. So I think we have to see how all that plays out, what the label really looks like. And certainly, we wish them luck because we do -- because I know they're listening to what I say, so good luck to them. But I also would say that if something comes along that can help patients, that's okay with us. EYLEA is a high bar, and people should be chasing that, we hope, for years to come. George, wanted to add one thing.

是的。因此，在糖尿病視網膜病變方面，我們與患者交談後發現，真正起作用的不僅僅是改善糖尿病視網膜病變，而是要預防威脅視力的糖尿病視網膜病變、威脅視力的併發症以及威脅視力的疾病的發生。然後，我們將在今年稍後查看來自 PANORAMA 研究的數據。但我認為這和其他市場沒什麼兩樣。我的意思是，如果你回顧一下——我記得我們的董事長羅伊·瓦格洛斯告訴我，當他推出第一種他汀類藥物時，心臟病專家告訴他，“嗯，其實沒有必要使用他汀類藥物。”“我們可以透過飲食和運動來控制這一切”，這是當時的主流觀點。所以，我們需要做一些工作，才能根據數據改變醫療實務。這並非一朝一夕就能完成的。這需要非常強大的數據和非常強大的商業努力。我們很高興看到 Marion 如此迅速地融入組織中，她也把這視為對我們來說非常重要的事情。因此，我們期待在未來的幾年裡，在這個領域取得成功。最近，一家小型公司推出了一款無需連接線的設備，該設備可以診斷糖尿病視網膜病變，並判斷您是否需要緊急就診視網膜專家——它可以放在藥店裡，可以放在您的全科診所裡，可以放在您的眼科醫生那裡，可以放在驗光師那裡，而且它已經獲得了批准。它不需要醫生來操作。你只需拍攝一張未散瞳的視網膜照片，然後——他們發現了一些驚人的數據，FDA據此批准了該藥物。我認為，在進行廣泛篩檢的情況下，這種疾病的診斷率仍然很低，這一點值得進一步探討。還有許多其他努力也是為了做同樣的事情，例如在機器學習或你所說的人工智慧領域。所以我們認為——當你有了治療方法，並且我們有了廣泛的適應症標籤，那麼你就可以開始向真正能從中受益的人群施壓，我認為這樣的人群有很多。就RTH數據而言，我沒看到什麼新內容。我聽說，在那些能夠堅持完成 12 週資料調查的人中，大約有 80% 的人能夠堅持完成 12 週資料調查。但歸根結底，你可以按照你想要的任何方式對這些數據進行切片。大約有 50% 的人可以每 12 週進行一次評估，而且根據——他們還沒有確定具體人選，因為如果你仔細觀察，那些在 12 週時沒有成功的人都是那些失敗的人——我認為視力嚴重受損是其中一個標準。所以我覺得我們得看看這一切會如何發展，看看這個標籤最終會是什麼樣子。當然，我們祝他們好運，因為我們真心希望他們好運——因為我知道他們在聽我的話，所以祝他們好運。但我還要說，如果有什麼方法可以幫助病人，我們當然樂意接受。EYLEA 樹立了一個很高的標準，我們希望在未來的幾年裡，人們都能朝著這個標準努力。喬治還想補充一點。

Yes. I wanted to expand on one thing that Len said. And Phil, you referred to the fact that in some ways doctors are perhaps a little cautious about treating patients with diabetic retinopathy and they have views on that. I think one key aspect of the studies that we're undertaking right now sort of like what we did with Praluent, is to define the patients who are at the highest risk of vision-threatening complications. So you might imagine that everybody, patients and doctors, would be much more interested in using a very effective preventative therapy if they knew they had a very, very high risk of having a catastrophic event that could cost them their vision. So a part of the aspect of our studies is not only to show that we're effective at preventing these events but identifying the segment of the population that is at highest need for needing such a therapy because they are at such a high risk.

是的。我想就 Len 所說的一點進行補充說明。菲爾，你提到過，在某些方面，醫生可能對治療糖尿病視網膜病變患者有些謹慎，他們對此有一些看法。我認為我們目前正在進行的研究（有點像我們之前對 Praluent 所做的研究）的一個關鍵方面是確定哪些患者最有可能出現威脅視力的併發症。因此，你可以想像，如果病人和醫生都知道自己有很高的風險發生可能導致失明的災難性事件，那麼他們就會更有興趣使用非常有效的預防性療法。因此，我們研究的部分目的不僅在於證明我們能夠有效預防這些事件，還在於確定最需要這種療法的群體，因為他們的風險非常高。

Next, we have Cory Kasimov from JPMorgan.

接下來，我們請到了摩根大通的科里·卡西莫夫。

I wanted to ask about how we should be thinking with regards to the reimbursement landscape with PCSK9s going forward? Should we expect more exclusive contracts with payers similar to the one announced with ESI? And maybe more broadly along those lines, are you getting the sense of how payers are thinking about the best way to define a high-risk patient population that would benefit most from Praluent?

我想請教一下，關於PCSK9抑制劑的報銷問題，我們該如何看待？我們是否應該期待更多類似與 ESI 簽訂的獨家合約？更廣泛地說，您是否了解支付方正在如何思考如何最好地定義能夠從 Praluent 中獲益最多的高風險患者群體？

So this is obviously a highly competitive space. There is another PCSK9 inhibitor out there obviously. So we can't sort of peel back too much, but we are excited about the fact that there is a possibility to improve the access. Make it easier for patients to get the prescription that the doctor writes, that it will be approved and make it so that patients can afford it. We also -- the third pillar of all that, which I don't want to get lost, is we want to make sure that there is some profit left for the innovators, on both sides, so that we don't wind up racing to a place where there is no profit. So it's a delicate competitive marketplace. That's about all we can say out there, but we're working hard to get access and affordability.

所以這顯然是一個競爭非常激烈的領域。顯然，市面上還有另一種PCSK9抑制劑。所以我們不能透露太多，但我們很高興有可能改善這種便利性。讓患者更容易獲得醫生開立的處方，確保處方獲得批准，並確保患者能夠負擔得起。我們還有第三個支柱，我不想忽略這一點，那就是我們希望確保雙方的創新者都能獲得一些利潤，這樣我們就不會最終陷入無利可圖的境地。所以這是一個競爭激烈的微妙市場。我們目前只能透露這麼多，但我們正在努力實現普及和價格合理。

And also, in the interest of time, this will be our last question but we will be available to answer questions following this call. So please send me an e-mail, and we'll set some time up for a follow-up call.

另外，為了節省時間，這將是我們的最後一個問題，但通話結束後我們仍會回答其他問題。所以請給我發封郵件，我們安排時間進行後續通話。

We have Geoff Meacham from Barclays.

我們請到了來自巴克萊銀行的傑夫‧米查姆。

We didn't hear you. Great, last question.

我們沒聽到你說話。好的，最後一個問題。

Geoff, we lost you.

傑夫，我們失去了你。

Well, let me ask the question for Geoff. That was a great quarter, Len, thanks very much for all of that, and it's fairly self-explanatory. All right. I think that wraps it up.

那我就替傑夫問個問題吧。Len，這個季度表現很棒，非常感謝你所做的一切，這其實不言自明。好的。我想這就是全部內容了。

Operator, that concludes our call today.

接線員，今天的通話到此結束。

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

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