雷傑納榮製藥 (REGN) 2020 Q2 法說會逐字稿

Ladies and gentlemen, thank you for standing by, and welcome to the Regeneron Pharmaceuticals Q2 2020 Earnings Conference Call. (Operator Instructions) Please be advised, today's call is being recorded. (Operator Instructions) Thank you.

女士們、先生們，感謝您的耐心等待，歡迎參加再生元製藥公司2020年第二季財報電話會議。 （操作說明）請注意，本次電話會議正在錄音。 （操作說明）謝謝。

Justin Holko, I will now turn the call over to you.

賈斯汀·霍爾科，現在我把通話交給你了。

Thank you, Stephanie. Good morning, good afternoon and good evening to everyone listening around the globe. Thank you for your interest in Regeneron Pharmaceuticals and welcome to the Second Quarter

謝謝斯蒂芬妮。祝福全球各地的聽眾好友們早安、午好、晚安。感謝您對再生元製藥的關注，歡迎收聽第二季節目。

2020 Conference Call. An archive of this webcast will be available on our website.

2020年電話會議。本次網路直播的存檔將在我們的網站上提供。

Joining me today on the call are Dr. Leonard Schleifer, Founder, President and Chief Executive Officer; Dr. George Yancopoulos, Co-Founder, President and Chief Scientific Officer; Marion McCourt, Senior Vice President and Head of

今天與我一起參加電話會議的有：創始人、總裁兼首席執行官倫納德·施萊弗博士；聯合創始人、總裁兼首席科學官喬治·揚科波洛斯博士；高級副總裁兼負責人瑪麗昂·麥考特。

Commercial; and Bob Landry, Executive Vice President and Chief Financial Officer. After our prepared remarks, we will open the call for Q&A.

商業方面；以及執行副總裁兼財務長鮑勃·蘭德里。在我們發言結束後，我們將進入問答環節。

I would also like to remind you that remarks made on today's call include forward-looking statements about Regeneron. Such statements may include, but are not limited to, those related to Regeneron and its products and businesses, financial forecast and guidance, development programs and related anticipated milestones, collaborations, finances, regulatory matters, payer coverage and reimbursement issues, intellectual property, pending litigation and other proceedings 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 the 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, 2020, which has been filed with the SEC today. Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

我還要提醒各位，今天電話會議的發言包含Regeneron的前瞻性聲明。這些陳述可能包括但不限於與Regeneron及其產品和業務、財務預測和指導、研發項目及相關預期里程碑、合作、財務、監管事宜、支付方覆蓋範圍和報銷問題、知識產權、未決訴訟和其他程序以及競爭相關的陳述。每項前瞻性陳述均受風險和不確定性的影響，這些風險和不確定性可能導致實際結果和事件與陳述中預測的結果和事件有重大差異。有關這些風險和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2020年6月30日的季度報告（10-Q表格），該報告已於今日提交給美國證券交易委員會。 Regeneron不承擔任何更新任何前瞻性聲明的義務，無論是因為新資訊、未來事件或其他原因。

In addition, please note that GAAP and non-GAAP measures will be discussed 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.

此外，請注意，今天的電話會議將討論GAAP和非GAAP財務指標。有關我們使用非GAAP財務指標以及這些指標與GAAP的調節表的信息，請參閱我們網站上發布的財務業績新聞稿。電話會議結束後，Bob Landry和投資者關係團隊將解答您的其他問題。

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, and thanks to everyone for joining the call. I hope all of you are staying safe and well. We very much appreciate your efforts to join given the pandemic conditions and even on top of that, in Northeast, some power disruption from the storm. But business continues.

謝謝賈斯汀，也謝謝各位參加這次電話會議。希望大家都平安健康。考慮到疫情情勢，再加上東北地區部分地區因風暴而停電，我們非常感謝大家抽出時間參加會議。但一切照常進行。

We had an eventful and productive second quarter in terms of financial results, business development and corporate accomplishments. In the second quarter, our results demonstrated resilience and strength despite the impact of the ongoing COVID-19 pandemic.

在財務業績、業務發展和公司成就方面，我們度過了充實而富有成效的第二季。儘管受到新冠疫情持續的影響，我們的業績仍展現出強大的韌性和實力。

In addition to driving double-digit top and bottom line growth, we continue to deliver meaningful advances in our broad and innovative pipeline as well as in our fight against COVID-19 with our novel antibody cocktail. Regeneron continues to execute well in this unprecedented time for our company, our nation and the world.

除了實現兩位數的營收和利潤增長外，我們還在廣泛而創新的產品線以及利用新型抗體雞尾酒療法對抗新冠肺炎方面持續取得重大進展。在公司、國家乃至全球面臨前所未有的挑戰之際，Regeneron 依然保持著良好的營運表現。

Starting with our products. EYLEA global net product sales were $1.75 billion in the second quarter, a modest decline of 6% compared to the prior year. In the U.S., we generated sales of $1.11 billion with a pronounced and sustained rebound in demand in May and June, following the decline in sales we experienced in early April. This rebound has continued into July, and demand is now approaching pre-COVID levels. The efficacy, safety and convenience of EYLEA have proven to be even more valuable in the world of COVID-19. As you'll hear from Marion, EYLEA outperformed the broader anti-VEGF class this quarter.

首先來看我們的產品。安禮製藥第二季全球淨產品銷售額為17.5億美元，較上年同期略為下降6%。在美國，我們的銷售額為11.1億美元，在4月初銷售額下滑之後，5月和6月的需求出現了顯著且持續的反彈。這種反彈動能延續到了7月，目前需求已接近新冠疫情前的水準。在新冠疫情肆虐的當下，安禮製藥的有效性、安全性和便利性顯得格外重要。正如您將從Marion那裡聽到的，安禮製藥本季的表現優於其他抗VEGF藥物。

Demand for Dupixent also proved to be robust in the second quarter with global sales growth of 70% compared to last year. Sales were nearly $1 billion on continued market penetration in atopic dermatitis, asthma and new launches. Adding to the Dupixent momentum, the FDA approved a new indication for atopic dermatitis in children aged 6 to 11. Furthermore, we demonstrated dramatic results in eosinophilic esophagitis where patients reported a nearly 70% reduction in symptoms, further exemplifying the potential of Dupixent to bend the arc of certain Type 2 inflammatory diseases. We look forward to additional Dupixent milestones, including an upcoming Phase III readout in pediatric asthma and enrollment of a second Phase III study in chronic obstructive pulmonary disease. We and our patients and customers have a tremendous amount of enthusiasm for this product, and we are still in the early days of unlocking its full potential with our partner, Sanofi.

第二季度，Dupixent的需求依然強勁，全球銷售額較去年同期成長70%。由於在異位性皮膚炎、氣喘和新上市產品領域的持續市場滲透，銷售額接近10億美元。此外，FDA批准了Dupixent用於治療6至11歲兒童異位性皮膚炎的新適應症，進一步推動了Dupixent的發展動能。同時，我們在嗜酸性食道炎的治療中也取得了顯著療效，患者症狀減輕近70%，這進一步證明了Dupixent在改善某些第二型發炎性疾病的潛力。我們期待Dupixent取得更多里程碑式的進展，包括即將公佈的兒童氣喘III期臨床試驗結果以及慢性阻塞性肺病第二項III期臨床試驗的患者招募。我們、我們的患者和客戶都對這款產品充滿熱情，我們正與合作夥伴賽諾菲攜手，努力挖掘其全部潛力。

In oncology, Libtayo is the leading systemic treatment for cutaneous squamous cell carcinoma. We are seeking approvals in basal cell carcinoma and non-small cell lung cancer with regulatory filings to be submitted imminently. With our chemotherapy combination study in non-small cell lung cancer nearing full enrollment, our excitement for Libtayo continues to grow. Beyond Libtayo, we are broadening and advancing our bispecifics portfolio, generating further momentum for our oncology strategy.

在腫瘤領域，Libtayo是治療皮膚鱗狀細胞癌的領先全身性治療藥物。我們正在尋求Libtayo在基底細胞癌和非小細胞肺癌領域的上市許可，相關監管文件即將提交。隨著Libtayo合併化療治療非小細胞肺癌的研究接近完成病患招募，我們對Libtayo的信心與日俱增。除了Libtayo之外，我們還在拓展和推進雙特異性抗體產品組合，這將進一步推動我們的腫瘤策略發展。

Turning to our efforts to fight COVID-19. We are advancing the development of a novel antibody cocktail known as REGN-COV2 that may both treat and prevent infection from the SARS-CoV-2 virus. We are now in Phase II and Phase III trials and hope to generate initial data by the end of September, as George will discuss in further detail. We also signed 2 major agreements in recent weeks. We announced a $450 million agreement with BARDA and the U.S. Department of Defense to manufacture REGN-COV2. We also signed a 6-year $345 million agreement with BARDA for our novel Ebola antibody cocktail, further demonstrating the potential of our end-to-end technologies to deliver shareholder value in addressing infectious disease threats.

接下來談談我們對抗新冠肺炎疫情的努力。我們正在推進一種名為REGN-COV2的新型抗體雞尾酒療法的研發，該療法有望治療和預防SARS-CoV-2病毒感染。目前，該療法已進入第二期和第三期臨床試驗階段，我們希望在9月底前獲得初步數據，喬治將對此進行更詳細的闡述。此外，我們最近幾週還簽署了兩項重要協議。我們宣布與美國生物醫學高級研究與發展局（BARDA）和美國國防部達成一項價值4.5億美元的協議，用於生產REGN-COV2。我們還與BARDA簽署了一項為期6年、價值3.45億美元的協議，用於生產我們研發的新型伊波拉抗體雞尾酒療法。這進一步證明了我們端到端技術在應對傳染病威脅方面為股東創造價值的潛力。

Finally, on the corporate front. We completed a large secondary offering of more than 13 million shares of our common stock held by Sanofi. Using our strong balance sheet, we also repurchased $5 billion or 9.8 million shares from Sanofi, effectively eliminating their ownership position in our company and demonstrating our confidence in the trajectory of our business. For Regeneron shareholders, this transaction provided immediate accretion and removed a significant overhang related to the expiration of Sanofi's lockup period at the end of this year. Regeneron is a business that is indeed firing on all cylinders. We thank all of our colleagues across the company who have been working with resolve and resilience in these extraordinary times of the pandemic. Our strong business performance, cash flow, balance sheet and advancement of the next generation of innovations for important medical needs has us positioned to weather COVID-19 and emerge from the pandemic to drive continued long-term growth.

最後，在公司層面。我們完成了由賽諾菲持有的超過1300萬股普通股的大規模二次發行。憑藉我們穩健的資產負債表，我們也從賽諾菲回購了價值50億美元（約980萬股）的股票，有效地消除了賽諾菲在我們公司的持股，並展現了我們對公司發展前景的信心。對於Regeneron的股東而言，此次交易帶來了即時收益成長，並消除了賽諾菲的禁售期將於今年年底到期所帶來的重大風險。 Regeneron的業務確實正處於全面高速運轉狀態。我們感謝公司所有同事在疫情肆虐的特殊時期所展現的堅定決心與頑強毅力。我們強勁的業務表現、充裕的現金流、穩健的資產負債表以及在滿足重要醫療需求的下一代創新技術方面的進展，使我們能夠抵禦新冠疫情的衝擊，並在疫情后實現持續的長期增長。

Now I'll turn the call over to George.

現在我把電話交給喬治。

Thank you, Len.

謝謝你，Len。

And with all of us still in the throes of the COVID-19 epidemic, I will start with an update on our antiviral antibody cocktail that has the potential to both possibly protect against infection and also treat those already infected. Based on our Ebola program, our new nonhuman primate data for our COVID-19 cocktail as well as our understanding of the immune response, we believe that our COVID-19 treatment is well positioned to help patients prior to an early on infection. We initiated our clinical program in June, barely 5 months after we started this treatment -- developing this treatment. Our rapid time line was possible due to our VelociSuite technologies, which we developed in-house over decades to allow for specific turnkey disease interventions and we recently applied to develop our similar approach against Ebola, which we hope will prove to be the first treatment approved for this disease with a PDUFA date in October.

在我們所有人仍深陷新冠肺炎疫情之際，我將首先介紹我們的抗病毒抗體雞尾酒療法的最新進展。該療法可望預防感染，並能治療已感染者。基於我們伊波拉病毒計畫、我們針對新冠肺炎雞尾酒療法獲得的最新非人靈長類動物數據，以及我們對免疫反應的理解，我們相信我們的新冠肺炎療法能夠幫助患者在早期感染前進行預防。我們在6月啟動了臨床試驗項目，距離我們開始研發該療法僅5個月。我們之所以能夠如此快速地推進研發，得益於我們自主研發的VelociSuite技術。這項技術歷經數十年研發，能夠實現特定疾病的一站式介入。我們最近已申請開發針對伊波拉病毒的類似療法，並希望它能成為首個獲準用於治療伊波拉病毒的療法，預計10月將獲得PDUFA批准。

We are currently conducting 4 trials of Regeneron COV2, our antibody cocktail: one in hospitalized COVID-19 patients; a second, ambulatory study in outpatients who are diagnosed with COVID-19; a third, preventative study in household contacts of COVID-19 patients being carried out in collaboration with the National Institute of Allergy and Infectious Disease; and a fourth multidose healthy volunteer study. Our studies are adaptive in nature as we learn more about the virus in our antibody cocktail, and other studies are being planned as well. All of these studies have passed several safety assessments with no safety concerns observed to date. Despite the challenging environment in which these studies are being conducted, we are targeting to report initial virology and biomarker data from the treatment studies by the end of September with clinical outcome data to follow as enrollment progresses.

我們目前正在進行四項Regeneron COV2（我們的抗體雞尾酒療法）的臨床試驗：一項針對住院COVID-19患者；一項針對門診COVID-19確診患者的門診研究；一項與美國國家過敏症和傳染病研究所合作開展的針對COVID-19患者家庭密切接觸者的預防性研究；隨著我們對抗體雞尾酒療法中病毒的了解不斷深入，我們的研究也不斷調整，我們也正在計劃進行其他研究。所有這些研究均已通過多項安全性評估，迄今未觀察到任何安全性問題。儘管這些研究的進行環境充滿挑戰，但我們計劃在9月底前公佈治療研究的初步病毒學和生物標記數據，並隨著入組進展陸續公佈臨床結果數據。

In June, we published 2 important papers in Science on our antibody cocktail in which we described the details of how the 2 antibodies in our cocktail block the coronavirus spike protein and importantly, highlighted the significance of using an antibody cocktail versus a single antibody approach. We showed that the cocktail approach avoided viral escape due to viral mutation, which rapidly occurred when using single antibody approaches. In addition, we have recently generated important data in nonhuman primates, which has been posted on bioarchives. These studies showed that in this setting, our antibody cocktail cannot only effectively prevent infection primates, matching or exceeding recently published prevention data achieved with vaccine approaches, but also that our cocktail can treat those already infected by accelerating viral elimination.

今年六月，我們在《科學》雜誌上發表了兩篇關於抗體雞尾酒療法的重要論文。論文中，我們詳細闡述了雞尾酒療法中兩種抗體如何阻斷冠狀病毒的刺突蛋白，並著重強調了使用抗體雞尾酒療法相對於單一抗體療法的優勢。我們證明，雞尾酒療法能夠避免因病毒變異而導致的病毒逃逸，而單一抗體療法則會迅速出現這種情況。此外，我們近期在非人靈長類動物身上獲得了重要數據，這些數據已發佈在生物檔案庫中。這些研究表明，在非人靈長類動物模型中，我們的抗體雞尾酒療法不僅能夠有效預防感染，其預防效果與近期發表的疫苗療法相當甚至更優，而且還能透過加速病毒清除來治療已感染的動物。

I next want to highlight the outside support we have received for our strategy. In addition to conducting our Phase III prevention study in collaboration with the NIAID, which subsequently expands our reach to investigate our cocktail in the preventative setting, we recently signed a manufacturing contract with BARDA as part of Operation Warp Speed to make initial lots of our cocktail at risk so the drug could be available as soon as possible, if proven efficacious and approved by the FDA. While we are all hoping that vaccines prove successful, and we ourselves are partnering on some novel second-generation vaccine approaches, we believe that our neutralizing antibody cocktail could play an important role as a rapid first line in defense in those for whom a vaccine is not available and in the long term, could also provide protection for those least likely to respond well to a vaccine, such as the elderly and immunocompromised. Moreover, unlike a vaccine and as supported by our initial primate studies, our cocktail may not only prevent infection, but could also have the potential to treat those already infected.

接下來，我想重點介紹我們策略所獲得的外部支持。除了與美國國家過敏症和傳染病研究所 (NIAID) 合作開展 III 期預防研究（這將進一步拓展我們在預防領域研究該混合療法的應用範圍）之外，我們最近還與生物醫學高級研究與發展局 (BARDA) 簽署了一份生產合同，作為“曲速行動”(Operation Warp Speed) 的一部分，以風險承擔的方式批准後，盡快投入使用。雖然我們都希望疫苗能夠成功，而且我們自己也在合作研發一些新型的第二代疫苗，但我們相信，我們的中和抗體混合療法可以在疫苗尚未普及的人群中發揮重要的快速第一道防線作用，並且從長遠來看，它還可以為那些最不可能對疫苗產生良好反應的人群（例如老年人和免疫功能低下者）提供保護。此外，與疫苗不同，正如我們最初的靈長類動物研究所所支持的那樣，我們的混合療法不僅可以預防感染，還有可能治療已感染者。

Moving on to our efforts outside of COVID-19 and starting with Dupixent. The demonstrated safety and efficacy of Dupixent are further bolstered by the recent FDA approval in children with moderate-to-severe atopic dermatitis, children as young as 6 years old. And we are not stopping there as we are conducting a study in even younger atopic dermatitis patients. And for children with asthma, we plan to submit a BLA supplement for approval in pediatric asthma by the end of the year, pending upcoming Phase III data. We're also enhancing convenience for all patients with the recent FDA approval of our 300-milligram auto-injector. Outside of the United States, Dupixent was approved in China recently, which represents a major milestone as we work to ensure patients everywhere have access to this life-changing medicine.

接下來，我們來看看除新冠肺炎疫情之外的其他進展，首先是Dupixent。 Dupixent的安全性和有效性已得到證實，近期FDA批准用於治療中重度異位性皮膚炎患兒，包括6歲及以上的兒童，這進一步鞏固了Dupixent的療效。我們並未止步於此，目前正在進行一項針對更小年齡異位性皮膚炎患者的研究。對於氣喘兒童，我們計劃在年底前提交生物製品許可申請（BLA）補充申請，以期獲得批准用於治療兒童氣喘，具體審批時間取決於即將公佈的III期臨床試驗數據。此外，我們近期也批准了300毫克自動注射器，這將為所有患者帶來更大的用藥便利。在美國以外，Dupixent近期在中國獲批上市，這是我們致力於確保全球患者都能獲得這種改變生命的藥物的重要里程碑。

Our Dupixent clinical program continues to deliver positive results in additional Type 2 inflammatory indications. In May, we announced that we met the primary and key secondary end points in Part A of our pivotal trial in eosinophilic esophagitis. Patients treated with Dupixent demonstrated significant clinical and anatomic improvements with almost a 70% reduction in disease symptoms compared to an approximate 30% reduction for patients on placebo, as demonstrated by the dysphasia symptom questionnaire. We are currently enrolling Part B of this trial and communicating with regulators about filing requirements for this indication. In addition, the first pivotal Dupixent trial in patients with chronic obstructive pulmonary disease typified by Type 2 inflammation, or Type 2 COPD, completed a prespecified analysis by the Independent Data Monitoring Committee requiring a certain threshold reduction in exacerbations, which was met and, thus, triggered opening a second pivotal trial for this potential indication. Approval in Type 2 COPD would unlock another important opportunity for Dupixent to help patients with Type 2 inflammatory disease who currently have limited options.

我們的Dupixent臨床計畫在其他2型發炎適應症方面持續取得正面成果。 5月，我們宣布，在嗜酸性食道炎關鍵性試驗A部分中，我們達到了主要終點和關鍵次要終點。接受Dupixent治療的患者在臨床和解剖學方面均表現出顯著改善，疾病症狀較安慰劑組患者減少了近70%（約30%），這透過失語症狀問卷調查得以證實。我們目前正在進行此試驗的B部分，並與監管機構溝通，以了解該適應症的申報要求。此外，首個針對以2型發炎為特徵的慢性阻塞性肺病（COPD）患者的關鍵性Dupixent試驗已完成獨立資料監察委員會預先設定的分析，該分析要求達到一定的急性加重次數減少閾值，而該閾值已達到，因此啟動了針對該潛在適應症的第二個關鍵性試驗。如果 Dupixent 核准用於治療第 2 型 COPD，將為 Dupixent 開啟另一個重要的機會，幫助目前治療選擇有限的 2 型發炎性疾病患者。

Moving on to our oncology portfolio and starting with our PD-1 antibody, Libtayo. At the virtual ASCO meeting, we presented a clinically meaningful cutaneous squamous cell carcinoma data follow-up -- followed by a label update as well, as reported at ASCO, with up to 3 years of follow-up. While the overall response rates remain stable, approaching 50%, the complete response rates have climbed to 20% in metastatic CSCC, increasing from the 7% rate reported in the initial primary analysis, providing one of the most dramatic examples of ongoing and prolonged benefit from an immunotherapy treatment. Moreover, these data firmly established Libtayo as first in class for this dermato-oncology cancer setting with compelling long-term clinical data. In addition, last quarter, we announced positive first-in-class data for a second dermato-oncology indication, that is basal cell carcinoma, which we will be submitting for regulatory review.

接下來，我們來談談腫瘤產品組合，首先是我們的PD-1抗體藥物Libtayo。在虛擬的ASCO會議上，我們發表了具有臨床意義的皮膚鱗狀細胞癌（CSCC）追蹤數據，並在ASCO會議上報告了該藥物的標籤更新，追蹤時間長達3年。雖然整體緩解率保持穩定，接近50%，但轉移性CSCC的完全緩解率已攀升至20%，高於最初主要分析中報告的7%，這為免疫療法持續且長期獲益提供了最顯著的例證之一。此外，這些數據憑藉著令人信服的長期臨床數據，確立了Libtayo在該皮膚腫瘤領域首創的地位。另外，上個季度，我們公佈了Libtayo在第二個皮膚腫瘤適應症——基底細胞癌——方面的積極首創數據，我們將提交監管部門進行審查。

Finally, we're excited about the opportunity for Libtayo in non-small cell lung cancer based on our recent positive Phase III trial with Libtayo as monotherapy in PD-L1 high patients, which we'll also be submitting for regulatory review. And we have completed screening patients for enrollment in our follow-on chemo combination study in lung cancer. Libtayo is foundational to our oncology strategy, and we are making significant progress with Libtayo on skin cancers, lung cancers and our numerous combination and collaborative studies.

最後，我們非常高興地宣布，Libtayo有望應用於非小細胞肺癌領域。這得益於我們近期在PD-L1高表達患者中開展的Libtayo單藥治療III期臨床試驗取得的積極成果，該試驗結果也將提交監管機構審批。此外，我們已完成後續肺癌化療聯合治療研究的患者入組篩選工作。 Libtayo是我們腫瘤治療策略的基石，我們在皮膚癌、肺癌以及眾多聯合治療和合作研究中均取得了顯著進展。

Our CD3 bispecifics clinical program is moving forward despite operational challenges imposed by the COVID-19 pandemic. Regeneron 1979, our CD20xCD3 bispecifics, has shown robust efficacy in both follicular lymphoma and more aggressive diseases, including diffused large B-cell lymphoma. Our potentially pivotal Phase II study continues to enroll globally, and we are having productive discussions with regulators to expand the registrational program with combinations and in earlier lines of treatment. We are preparing to explore novel combinations, including a combination from our novel class of costimulatory bispecifics that is one targeting B-cell specifically. We recently published a second major paper featured on the cover of Science Translational Medicine in June describing how these costimulatory bispecifics can synergize not only with CD3 bispecifics, but also with PD-1 blockers.

儘管受到新冠疫情帶來的營運挑戰，我們的CD3雙特異性抗體臨床計畫仍在穩步推進。我們的CD20xCD3雙特異性抗體Regeneron 1979已在濾泡性淋巴瘤和更具侵襲性的疾病（包括瀰漫性大B細胞淋巴瘤）中展現出顯著療效。我們具有潛在關鍵性的II期臨床試驗正在全球範圍內持續招募患者，並且我們正與監管機構進行富有成效的磋商，以期通過聯合用藥和更早期的治療方案來擴展註冊項目。我們正準備探索新的聯合療法，包括一種來自我們新型共刺激雙特異性抗體的聯合療法，該療法特異性靶向B細胞。我們近期發表了第二篇重要論文，該論文於6月登上《科學轉化醫學》雜誌封面，闡述了這些共刺激雙特異性抗體如何不僅與CD3雙特異性抗體產生協同作用，還能與PD-1阻斷劑產生協同作用。

Finally, we are actively working on subcutaneous delivery of this potentially important drug candidate. Our BCMAxCD3 bispecific is moving forward, and we are planning to initiate potentially pivotal studies in various multiple myeloma settings. Moreover, we intend to explore standard novel combinations, including with a costimulatory bispecific targeting plasma cells. We expect to provide updates for both our CD20 and BCMA programs at ASH later this year.

最後，我們正在積極研發這種潛在重要候選藥物的皮下給藥途徑。我們的BCMAxCD3雙特異性抗體研發進展順利，並計劃在多種多發性骨髓瘤模型中啟動關鍵性研究。此外，我們還計劃探索新的標準聯合療法，包括與靶向漿細胞的共刺激雙特異性抗體聯合使用。我們預計將在今年稍後的ASH會議上公佈CD20和BCMA項目的最新進展。

I would like to expand a bit on our costimulatory bispecific effort as it represents an important example of the ongoing innovation in oncology for Regeneron. As I said, we are planning on combining such costims with both our CD20 and BCMA bispec programs for lymphoma and myeloma, but our first costimulatory bispecific is already in clinical development. This first-in-humans costim, PSMAxCD28, is in combination with Libtayo for prostate cancer and is continuing to enroll in the dose escalation stage of clinical investigation. We're also excited about 2 additional costim bispecifics scheduled to enter the clinic this year. These new costim trials include EGFRxCD28 in combination with Libtayo, which will be explored in several solid tumors, including lung cancer and head and neck cancer, as well as MUC16xCD28, which will be tested for patients with ovarian cancer as well as in other settings. Our MUC16 costim will be studied in combination with either Libtayo or our MUC16xCD3 bispecific, which is already in the clinic. The span of our toolkit enables us to explore these and many new combinations that based on preclinical evidence could provide meaningful advances for a wide variety of cancer patients.

我想就我們的共刺激雙特異性抗體研發工作做進一步闡述，因為它代表了再生元公司在腫瘤學領域持續創新的一個重要例證。正如我之前所說，我們計劃將這類共刺激抗體與我們針對淋巴瘤和骨髓瘤的CD20和BCMA雙特異性抗體項目相結合，但我們的首個共刺激雙特異性抗體已進入臨床開發階段。這款首個用於人體試驗的共刺激抗體PSMAxCD28，正與Libtayo聯合用於治療前列腺癌，目前正處於劑量遞增階段的臨床試驗中，並持續招募患者。此外，我們也對計劃於今年進入臨床試驗的另外兩種共刺激雙特異性抗體感到興奮。這些新的共刺激抗體試驗包括EGFRxCD28與Libtayo聯合用藥，該方案將在多種實體瘤中進行探索，包括肺癌和頭頸癌；以及MUC16xCD28，該方案將在卵巢癌患者以及其他適應症中進行測試。我們將研究MUC16共刺激劑與Libtayo或我們已進入臨床試驗階段的MUC16xCD3雙特異性抗體合併應用的效果。我們強大的藥物組合使我們能夠探索這些以及許多其他新的聯合療法，基於臨床前證據，這些療法有望為多種癌症患者帶來顯著的療效提升。

Moving on from oncology, I would like to provide an update on our fasinumab program. We have previously announced positive top line efficacy data in a fasinumab Phase III FACT long-term safety study or FACT LTS substudy. And today, we are announcing that 2 additional Phase III studies in patients with osteoarthritis pain, FACT OA1 and FACT OA2, met the co-primary efficacy end point for the fasinumab 1-milligram monthly dose versus placebo. The fasinumab 1-milligram monthly dose also showed nominally significant benefits in physical function in both trials and pain in 1 of the 2 trials when compared to the maximum FDA-approved doses of NSAIDs for osteoarthritis. The less frequent dose of fasinumab 1 milligram every 2 months used in an arm of the FACT OA1 trial showed numerical benefit over placebo, but did not achieve statistical significance. In initial safety analysis from the Phase III trials, there was an increase in arthropathies reported with fasinumab. In the FACT LTS substudy, there was increase in joint replacements with fasinumab 1-milligram monthly treatment during the off-drug follow-up period. Although this increase was not seen in the other trials to date, additional longer-term safety data from the ongoing trials is being collected and is expected to be reported early next year.

接下來，我想介紹一下我們的法西單抗項目。先前，我們已發表了法西單抗III期FACT長期安全性研究（或稱為FACT LTS子研究）的積極療效數據。今天，我們宣布兩項針對骨關節炎疼痛患者的III期研究（FACT OA1和FACT OA2）均達到了法西單抗每月1毫克劑量與安慰劑相比的共同主要療效終點。與FDA批准的用於治療骨關節炎的非類固醇抗發炎藥物（NSAIDs）最大劑量相比，法西單抗每月1毫克劑量在兩項試驗中均顯示出對身體功能的顯著改善，並在其中一項試驗中顯示出對疼痛的顯著改善。在FACT OA1試驗的一個治療組中，每2個月給予一次法西單抗1毫克的給藥頻率較低，雖然數值上優於安慰劑，但未達統計學意義。在III期臨床試驗的初步安全性分析中，法西單抗組報告的關節病變發生率增加。在FACT LTS子研究中，停藥追蹤期間，接受每月1毫克法西單抗治療的患者關節置換率增加。儘管迄今為止在其他試驗中未觀察到這種增加，但正在進行的試驗的更多長期安全性數據正在收集中，預計將於明年初公佈。

Finally, I would like to briefly address other exciting developments in our pipeline. We are planning to publish evinacumab results in homozygous familial hypercholesterolemia shortly, and we have submitted our applications to the FDA and to EMA. Regarding our garetosmab program for fibrodysplasia ossificans progressiva, or FOP, we are planning to submit data to regulatory authorities in the first quarter of next year, pending results from the crossover arm of our trial where placebo patients are now receiving active drug. Our hope is to replicate the dramatic 90% reduction in new lesion formation that we saw in the first part of the trial. At the European Hematology Association meeting in June, we presented promising pozelimab monotherapy interim results in paroxysmal nocturnal hemoglobinuria patients. We are hoping to start testing a combination with Alnylam's RNAi treatment, cemdisiran, by year-end. And last, but certainly not least, we are starting to enroll our Phase III studies of high-dose EYLEA in DME and wet AMD. High-dose EYLEA has the potential to reduce dosing frequency while maintaining the efficacy and safety of our medicine that is trusted by doctors and patients worldwide.

最後，我想簡要介紹一下我們研發管線中的其他一些令人振奮的進展。我們計劃近期發表evinacumab在純合子家族性高膽固醇血症的研究結果，並且已經向FDA和EMA提交了申請。關於我們用於治療進行性骨化性纖維發育不良症（FOP）的garetosmab項目，我們計劃在明年第一季度向監管機構提交數據，前提是獲得我們試驗交叉組（目前安慰劑組患者正在接受活性藥物治療）的結果。我們希望能夠重現試驗第一階段觀察到的新病灶形成顯著減少90%的效果。在6月份的歐洲血液學會會議上，我們展示了pozelimab單藥治療陣發性睡眠性血紅蛋白尿症患者的初步結果，結果令人鼓舞。我們希望在年底前開始測試pozelimab與Alnylam公司的RNAi療法cemdisiran的聯合用藥方案。最後，但同樣重要的是，我們即將啟動針對糖尿病性黃斑水腫（DME）和濕性老年黃斑部病變（AMD）的高劑量EYLEA III期臨床試驗。高劑量EYLEA有望在保持我們這款深受全球醫生和患者信賴的藥物的療效和安全性的同時，降低給藥頻率。

To conclude, our broad and diverse pipeline is growing and progressing even in this COVID-19 environment. I could not be prouder that even in these extraordinary and challenging times, our people are continuing to push on every front in our efforts to bring important new treatments to the patients who need them.

總之，即使在新冠疫情肆虐的當下，我們廣泛而多元化的研發管線仍在不斷發展壯大。我無比自豪的是，即便在如此特殊且充滿挑戰的時期，我們的員工依然在各方面不懈努力，致力於為亟需治療的患者帶來重要的全新療法。

I now turn over the call to Marion.

現在我把電話交給瑪莉安。

Thank you, George.

謝謝你，喬治。

Our second quarter business performance reflects the resilience and competitive strength of our core brands. EYLEA, Dupixent and Libtayo. We remain confident in our ability to navigate through COVID-19 and position our portfolio for future growth as demand recovers. I'm going to begin with EYLEA, which had $1.75 billion in global net sales. In the U.S., EYLEA net sales were $1.11 billion, which is just 4% lower than same quarter last year despite the impact of COVID-19.

我們第二季的業績體現了我們核心品牌——安禮 (EYLEA)、度普利 (Dupixent) 和利普泰 (Libtayo)——的韌性和競爭力。我們仍有信心應對新冠疫情帶來的挑戰，並隨著需求的復甦，調整產品組合以實現未來的成長。首先，我想談談安禮 (EYLEA)，其全球淨銷售額為 17.5 億美元。在美國，安禮 (EYLEA) 的淨銷售額為 11.1 億美元，儘管受到新冠疫情的影響，但僅比去年同期下降了 4%。

EYLEA outperformed the overall anti-VEGF market in the U.S. with continued share gains from both branded and unbranded competition. In fact, EYLEA's share of the branded U.S. market reached 73% of net sales for the quarter, solidifying our leadership position in the anti-VEGF market. The impact of COVID-19 on U.S. sales was saw predominantly in April. After this, sales improved throughout May and into June as retina specialists reopened offices and patient volume increased. The combination of 3 EYLEA attributes, differentiated efficacy, safety and dosing flexibility, are highly valuable in easing physician and patient burdens caused by the pandemic. Physicians may treat with extended dosing of up to 12 weeks in appropriate patients, and the recently launched prefilled syringe offers additional efficiencies for patient care. EYLEA demand continues to show steady improvement, and the volume of new patients in the market is approaching pre-pandemic levels. We're closely monitoring the recent resurgence of COVID-19. Under all scenarios, we remain highly committed to supporting the retina community through virtual and in-person platforms to sure the continuity of patient care.

在美國，EYLEA 的表現優於整體抗 VEGF 市場，其市佔率持續成長，超越了品牌藥和非品牌藥的競爭。事實上，EYLEA 在美國品牌藥市場的佔有率在本季達到了淨銷售額的 73%，鞏固了在抗 VEGF 市場的領先地位。新冠疫情對美國市場銷售的影響主要體現在 4 月。此後，隨著視網膜專科醫生重新開放診所，患者數量增加，5 月和 6 月的銷售額有所回升。 EYLEA 的三大優勢——差異化的療效、安全性和靈活的給藥方案——對於減輕疫情給醫生和患者帶來的負擔至關重要。醫生可以為合適的患者提供長達 12 週的延長給藥方案，而近期推出的預充式註射器則進一步提高了患者護理的效率。 EYLEA 的需求持續穩定成長，市場新患者數量正逐步恢復到疫情前的水準。我們正密切關注近期新冠肺炎疫情的再次爆發。無論情況如何，我們都將始終致力於透過線上和線下平台為視網膜病變患者群體提供支持，以確保患者護理的連續性。

In summary, we're encouraged by the rebound in EYLEA demand in recent months, and we will continue to advance efforts to support our customers and their patients during these unprecedented times.

總而言之，我們對近幾個月來安理國際藥品需求的反彈感到鼓舞，我們將繼續努力，在這段前所未有的時期為我們的客戶及其患者提供支援。

Turning next to Libtayo. Second quarter global net sales grew to $80 million with the U.S. contributing $63 million. In April, patient office visits declined and some infusion centers temporarily closed. This briefly impacted Libtayo demand, which rebounded during May and June. In the U.S., Libtayo advanced its leadership as the #1 systemic treatment for advanced cutaneous squamous cell carcinoma, or CSCC. Libtayo has experienced rapid growth in advanced CSCC with 70% of patients now treated with anti-PD-1 therapy. We expect future growth as Libtayo -- as the Libtayo competitive profile strengthens with new long-term data demonstrating longer durability, higher overall responses and nearly 3x the rate of complete responses based on additional years of follow-up.

接下來我們來看看利妥昔單抗（Libtayo）。第二季全球淨銷售額成長至 8,000 萬美元，其中美國貢獻了 6,300 萬美元。 4 月份，患者門診就診量下降，部分輸液中心暫時關閉。這短暫影響了利妥昔單抗的需求，但 5 月和 6 月需求有所回升。在美國，利妥昔單抗鞏固了其作為晚期皮膚鱗狀細胞癌（CSCC）首選全身治療藥物的領先地位。利妥昔單抗在晚期 CSCC 領域實現了快速成長，目前 70% 的患者正在接受抗 PD-1 療法治療。我們預計，隨著利妥昔單抗未來持續成長－新的長期數據顯示其療效更持久、整體緩解率更高，且基於額外追蹤年限的完全緩解率接近三倍，利妥昔單抗的競爭優勢將進一步增強。

Looking ahead, we are preparing for potential future launches with our collaborator, Sanofi, in both non-small cell lung cancer and basal cell carcinoma, both represent meaningful growth opportunities for Libtayo. The anti-PD-1 and PD-L1 market continues to grow at a significant pace with current annual net sales of nearly $25 billion. Non-small cell lung cancer is the largest opportunity within this market with more than 200,000 new diagnoses of lung cancer in the U.S. each year. Patients, payers and physicians prefer choice in determining the most appropriate treatment. And should Libtayo be approved, it has demonstrated very competitive clinical results to date in the advanced PD-1 positive patient population studied.

展望未來，我們正與合作夥伴賽諾菲共同籌備未來在非小細胞肺癌和基底細胞癌領域的潛在上市，這兩個領域都為Libtayo帶來了重要的成長機會。抗PD-1和PD-L1市場持續高速成長，目前年淨銷售額已接近250億美元。非小細胞肺癌是該市場中最大的成長點，美國每年新增肺癌病例超過20萬例。患者、支付者和醫生都希望在選擇最合適的治療方案時擁有更多選擇。如果Libtayo獲得批准，迄今為止，在已研究的晚期PD-1陽性患者族群中，它已展現出極具競爭力的臨床療效。

Finally, moving to Dupixent. Global net sales in the second quarter were $945 million, representing 70% growth compared to the prior year. In the U.S., broad-based growth across all approved indications contributed net sales of $770 million. Following an initial dip in mid-May, new patient starts have increased as physician offices reopened. Current weekly new patient starts have recovered to approximately 87% of pre-pandemic levels, a sign of robust demand for Dupixent. Dupixent's compelling clinical profile enables the product to thrive even in the current environment, Dupixent is administered at home and does not require laboratory testing or monitoring to initiate most new patients. Importantly, Dupixent is not an immunosuppressant, and we expect the U.S. launch of the 300-milligram prefilled pen in the third quarter, providing additional patient convenience and choice. Atopic dermatitis is Dupixent's largest indication and remains a significant growth driver. We continue to expand physician prescribing across both moderate and severe disease. To date, only a small percentage of biologic-eligible patients have been treated, leaving substantial opportunity for more patients to benefit. Additionally, new long-term data demonstrates sustained efficacy over a 3-year period, along with confirmed safety.

最後，我們來看看Dupixent。第二季全球淨銷售額為9.45億美元，年增70%。在美國，所有已核准適應症的全面成長貢獻了7.7億美元的淨銷售額。 5月中旬新患者用藥量出現短暫下滑後，隨著醫師診所重新開放，新患者用藥量回升。目前每週新患者用藥量已恢復至疫情前水準的約87%，顯示市場對Dupixent的需求強勁。 Dupixent優異的臨床特性使其即使在當前環境下也能蓬勃發展。 Dupixent可在家中給藥，大多數新患者無需實驗室檢測或監測即可開始使用。重要的是，Dupixent並非免疫抑制劑。我們預計在第三季在美國推出300毫克預填充注射筆，這將為患者提供更多便利和選擇。異位性皮膚炎是Dupixent最大的適應症，也是重要的成長動力。我們將繼續擴大醫生在中度和重度異位性皮膚炎患者的處方量。迄今為止，僅有少數符合生物製劑治療條件的患者接受了治療，這意味著還有大量患者有機會從中獲益。此外，新的長期數據顯示，該療法在三年內療效持續，且安全性已得到證實。

We also continue to expand into younger populations. The U.S. FDA recently approved Dupixent to treat children aged 6 to 11 years with moderate-to-severe atopic dermatitis, which impacts approximately 90,000 children in this country. Dupixent is the only biologic medicine approved for this population, and leading launch indicators are very encouraging. Many children suffering with moderate-to-severe atopic dermatitis are being treated by the same physicians who have extensive clinical experience with their adolescent and adult patients and have great confidence in the Dupixent safety profile.

我們也持續拓展年輕族群市場。美國FDA近期批准了Dupixent用於治療6至11歲中重度異位性皮膚炎患兒，影響著美國約9萬名兒童。 Dupixent是目前唯一獲準用於該族群的生物製劑，其主要上市指標令人鼓舞。許多患有中重度異位性皮膚炎的兒童正在接受同一批醫生的治療，這些醫生在治療青少年和成人患者方面擁有豐富的臨床經驗，並且對Dupixent的安全性充滿信心。

Dupixent also continues to outperform in asthma as measured by more new patient initiations over the last year compared to other biologic competitors. We see further opportunities to expand patient awareness of Dupixent in our national DTC campaign, which is underway. Among those already on treatment, COVID-19 has limited impact as patients adhere to their therapies to maintain and improve respiratory function.

在過去一年中，Dupixent 在氣喘治療領域持續表現優異，新增患者數量超過其他生物製劑競爭對手。我們正在進行全國性的直接面向消費者 (DTC) 推廣活動，旨在進一步提高患者對 Dupixent 的認知度。對於已接受治療的患者而言，由於他們堅持治療以維持和改善呼吸功能，COVID-19 對其影響有限。

Finally, we see strong uptake in chronic rhinosinusitis with nasal polyps. Since approval last year, patients have been initiated on Dupixent. Regardless of prior surgery, demand has increased among ENTs and allergists with the limited availability of elective surgeries in the last quarter. Overall, we see great opportunity for Dupixent, which is positioned for significant growth through expanded indications, age groups and geographies.

最後，我們看到Dupixent在慢性鼻竇炎伴隨鼻息肉患者的應用非常廣泛。自去年獲準以來，已有患者開始接受Dupixent治療。無論之前是否接受過手術，由於上個季度擇期手術機會有限，耳鼻喉科醫生和過敏科醫生對該藥的需求均有所增加。總體而言，我們認為Dupixent擁有巨大的發展潛力，其適應症、年齡層和地理範圍的擴大有望帶來顯著的成長。

In closing, our teams and business remain resilient as we execute on our strategy to deliver value for customers and stakeholders. Now I'll turn the call to Bob.

最後，我們團隊和業務依然保持韌性，我們將繼續執行策略，為客戶和利害關係人創造價值。現在，我將把發言權交給鮑伯。

Thank you, Marion.

謝謝你，瑪莉安。

For the second quarter of 2020, Regeneron delivered strong results on both the top and bottom line. Our continued ability to generate this year-over-year growth is an encouraging signal of our diversified growth potential now and beyond COVID-19. For the second quarter, total revenues grew 24% year-over-year to $1.95 billion driven by higher Sanofi collaboration revenues as a result of increasing Dupixent sales. Additionally, we recorded significant revenues associated with our infectious disease efforts against both Ebola and COVID-19. These revenues are recorded in our other revenue line. Non-GAAP diluted net income per share grew 19% year-over-year to $7.16 on non-GAAP net income of $854 million.

2020年第二季度，Regeneron在營收和利潤方面均取得了強勁的業績。我們持續實現同比增長的能力，令人鼓舞地表明了我們多元化的成長潛力，無論現在還是在新冠疫情之後，我們都擁有良好的發展前景。第二季度，總營收年增24%至19.5億美元，主要得益於與賽諾菲合作的Dupixent銷售成長帶來的營收增加。此外，我們也錄得了與對抗伊波拉病毒和新冠肺炎相關的重大傳染病收入。這些收入計入了其他收入項下。非GAAP攤薄後每股淨收益年增19%至7.16美元，非GAAP淨利為8.54億美元。

Since Marion discussed our U.S. EYLEA results, I will start with our Bayer and Sanofi collaborations. Starting with the Bayer collaboration. Ex U.S. EYLEA net product sales, which are reported to us by Bayer, were $641 million, representing a decline of 10% on a reported basis compared to the prior year due to the COVID-19 impact. Total Bayer collaboration revenue was $244 million, of which we recorded $231 million for our share of net profits from EYLEA sales outside the U.S. Total Sanofi collaboration revenue was $269 million in the second quarter. Our share of the profits from the commercialization of non-IO antibodies was $172 million. This compares favorably to profits of $39 million in the prior year period, which was driven by higher Dupixent profits.

既然Marion已經討論了我們在美國銷售的EYLEA的業績，我將首先談談我們與拜耳和賽諾菲的合作。先說拜耳的合作。拜耳向我們報告的除美國市場外，EYLEA的淨產品銷售額為6.41億美元，受新冠疫情影響，按報告基準計算，較上年同期下降10%。拜耳合作總收入為2.44億美元，其中我們計入了來自美國以外地區EYLEA銷售的2.31億美元淨利份額。第二季度，賽諾菲合作總收入為2.69億美元。我們從非免疫腫瘤抗體商業化中獲得的利潤份額為1.72億美元。相較於上年同期3,900萬美元的利潤，這一數字有所成長，上年同期利潤成長主要得益於Dupixent利潤的提高。

Before moving to expenses, I will discuss our second quarter 2020 other revenue line item in which we recorded $212 million, up sharply from the $20 million in the prior year period. The primary driver of the year-over-year increase is the recognition of $126 million associated with BARDA for our research and manufacturing efforts for both Ebola and COVID-19. We record R&D reimbursements from BARDA in other revenues.

在討論費用之前，我想先談談我們2020年第二季的其他收入項目，該項目收入為2.12億美元，較上年同期的2000萬美元大幅增長。年比成長的主要原因是確認了與美國生物醫學高級研究與發展局（BARDA）相關的1.26億美元收入，用於我們針對伊波拉病毒和新冠病毒的研究和生產工作。我們將BARDA的研發報銷款項計入其他收入。

Moving to our expense basis, starting with R&D. Non-GAAP R&D increased 36% year-over-year to $580 million driven by significant development costs for both our antibody cocktail and Kevzara clinical trials for COVID-19 in addition to higher count and increased clinical manufacturing activities, a portion of which were reimbursed by BARDA.

接下來我們來看費用基礎，首先是研發。非GAAP研發支出年增36%至5.8億美元，主要原因是我們的抗體雞尾酒療法和Kevzara COVID-19臨床試驗的重大研發成本，以及臨床生產活動數量的增加和規模擴大，其中一部分費用由BARDA報銷。

Next, non-GAAP SG&A expense increased 19% year-over-year to $301 million. The year-over-year increase was driven by the inclusion of Praluent commercialization costs in the U.S., higher contributions to nonprofit patient assistance organizations and higher headcount-related costs. Non-GAAP cost of collaboration and contract manufacturing was $173 million compared to $79 million in the second quarter of 2019. The year-over-year increase is due to manufacturing costs associated with higher Dupixent volumes sold by Sanofi, Ebola production and Praluent supply for Sanofi's ex U.S. markets.

其次，非GAAP銷售、管理及行政費用年增19%至3.01億美元。年比成長主要受以下因素影響：Praluent在美國的商業化成本計入、對非營利性病患援助組織的捐款增加以及與人員相關的成本上升。非GAAP合作及合約生產成本為1.73億美元，而2019年第二季為7,900萬美元。年比成長主要由於賽諾菲Dupixent銷售增加、伊波拉病毒生產以及為賽諾菲美國以外市場供應Praluent所導致的生產成本上升。

Turning now to taxes. The non-GAAP effective tax rate was 0.9% in the second quarter of 2020 compared to 19.1% in the second quarter of 2019. The lower tax rate versus last year was primarily due to increased tax benefits associated with stock option exercises in the realization of those benefits earlier in the calendar year compared to prior years.

接下來談談稅務方面。 2020年第二季的非GAAP實際稅率為0.9%，而2019年第二季為19.1%。稅率較上年同期降低的主要原因是，與往年相比，本年度較早實現股票選擇權行使所帶來的稅收優惠有所增加。

Shifting now to cash flow and the balance sheet. Year-to-date, Regeneron generated $1.34 billion in free cash flow. In the quarter, we spent $5 billion to repurchase approximately 9.8 million shares of our common stock as part of Sanofi's sale of substantially all of their equity stake in Regeneron. As Len mentioned, the secondary offering in repurchase were strategic transactions that provided Regeneron shareholders immediate accretion, removed uncertainty regarding Sanofi's equity position and is a testament to our confidence and the strength of our business now and in the future. We ended the quarter with cash and marketable securities of $5.7 billion and $1.5 billion in debt financing under a bridge loan related to the Sanofi stake repurchase.

現在來看現金流和資產負債表。今年迄今為止，Regeneron 已產生 13.4 億美元的自由現金流。本季度，我們斥資 50 億美元回購了約 980 萬股普通股，這是賽諾菲出售其在 Regeneron 的幾乎所有股權的一部分。正如 Len 所提到的，此次回購是策略性交易，它為 Regeneron 股東帶來了即時收益成長，消除了賽諾菲股權狀況的不確定性，也反映了我們對公司當前及未來業務實力的信心。本季末，我們持有現金及有價證券 57 億美元，另有 15 億美元的債務融資來自與賽諾菲股權回購相關的過橋貸款。

Now I'd like to spend a few moments to discuss the financial outlook for the remainder of the year. We maintained or lowered the midpoint of our guidance on several expense items. Please refer to our press release and financial disclosures for our entire updated 2020 guidance. Here, I will discuss the guidance items related to our increased efforts in the fight against COVID-19 as we leverage our end-to-end capabilities of drug discovery, development and manufacturing. We are updating our forecasted 2020 non-GAAP R&D expenses to be in the range of $2.27 billion to $2.37 billion. For COGS, we are raising our forecast for 2020 non-GAAP expenses to be in the range of $445 million to $485 million. The increase in both R&D and cost of goods sold guidance are related primarily to our efforts against COVID-19. For R&D, we anticipate that more than half of the increase to our 2020 R&D guidance will be reimbursed for COVID-19 efforts. Those reimbursements will continue to be recorded in other revenue. We're also providing updated guidance for our tax rate. We anticipate our updated 2020 non-GAAP effective tax guidance to be in the range of 10% to 12%.

現在我想花幾分鐘時間談談今年剩餘時間的財務展望。我們維持或下調了多項支出項目的預期中位數。請參閱我們的新聞稿和財務揭露文件，以了解我們更新後的2020年完整預期。在這裡，我將重點討論與我們加強抗擊新冠疫情力度相關的預期項目，我們將充分利用我們在藥物發現、開發和生產方面的端到端能力。我們將2020年非GAAP研發支出預期上調至22.7億美元至23.7億美元。對於銷售成本，我們將2020年非GAAP支出預期上調至4.45億美元至4.85億美元。研發支出和銷售成本預期的上調主要與我們對抗新冠疫情的努力有關。對於研發支出，我們預計2020年研發支出預期上修的一半以上將用於新冠疫情相關工作。這些報銷款項將繼續計入其他收入。同時，我們也更新了稅率指引。我們預計2020年非GAAP實際稅率指引將在10%至12%之間。

In conclusion, Regeneron's business remains healthy, and we continue to deliver strong year-over-year growth despite the global impact of COVID-19. Our strong balance sheet, improved competitive outlook, increasingly diversified commercial portfolio and robust pipeline position Regeneron very well for sustained long-term growth.

總之，儘管受到新冠疫情的全球影響，Regeneron的業務仍保持健康發展，並持續實現強勁的年成長。我們穩健的資產負債表、不斷改善的競爭前景、日益多元化的商業組合以及強大的研發管線，都為Regeneron的長期持續成長奠定了堅實的基礎。

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

現在，我想把電話轉回給賈斯汀。

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

謝謝鮑勃。史蒂芬妮，我們的發言到此結束。現在進入問答環節。 （操作員提示）請開始，史蒂芬妮。

(Operator Instructions) And your first question is from the line of Terence Flynn with Goldman Sachs.

（操作員說明）你的第一個問題來自高盛的 Terence Flynn。

Thanks for all your efforts on the COVID front. I just had one on the manufacturing side. I was wondering if you can give us any more detail about your manufacturing cost for the antibodies. Or if you could at least confirm that these are well below $100 per gram? And if you won't answer that question, I was just wondering, Marion, if any perspective you can share on the opportunity for Dupixent in China. And specifically, would you guys think NRDL reimbursement?

感謝您在新冠疫情所做的一切努力。我最近在生產方面有個問題。我想請您提供更多關於抗體生產成本的細節。或者，您能否至少確認一下成本是否遠低於每克100美元？如果您不方便回答這個問題，Marion，我還想請教您，您能否分享一下Dupixent在中國的市場前景？特別是，您認為它能獲得NRDL的報銷嗎？

Terence, it's Len. I don't think we can comment on our COGS. But Marion can certainly comment on China.

特倫斯，我是倫。我覺得我們不方便評論我們的成本。但瑪莉昂肯定可以評論中國的情況。

Sure. Very happy to. Terence, thank you for the question. We're really excited about the opportunity in China. And I'll also remind that Sanofi has the responsibility for China. We're very encouraged by the progress to date. And as it relates to specifics on reimbursement, I would guide asking our Sanofi colleagues to describe that in more detail. But as you know, tremendous market opportunity, incredible unmet need and a remarkable clinical profile, and we're really excited about the opportunity.

當然可以。非常樂意。特倫斯，謝謝你的提問。我們對在中國的發展機會感到非常興奮。我還要提醒大家，賽諾菲負責中國市場。我們對目前的進展感到非常鼓舞。至於具體的報銷細節，我建議你諮詢賽諾菲的同事，讓他們詳細解釋一下。但如你所知，中國市場潛力巨大，存在著巨大的未滿足需求，並且擁有卓越的臨床前景，我們對這個機會感到非常興奮。

Your next question is from the line of Geoffrey Porges with SVB Leerink.

你的下一個問題來自 SVB Leerink 的 Geoffrey Porges。

Congratulations on the results and all the progress in the quarter. Perhaps a few questions on the COVID program. George, you referred to the animal data and the high dose used, 50 milligrams per kilogram, is quite a lot of antibody. Could you give us a sense of, first, is that the dose that you expect to take forward in the pivotal trials for treatment? And how much lower could it be for prophylaxis? And secondly, if that indeed turns out to be the dose, could you give us some indication of the number of causes that you could envisage having supply for this year and the next year given the available capacity now?

恭喜你們所取得的成果以及本季所取得的所有進展。關於新冠疫​​情項目，我有幾個問題。喬治，你提到了動物實驗數據，以及使用的高劑量（每公斤50毫克），這確實是一個相當大的抗體劑量。首先，能否請你說明一下，這個劑量是否就是你們計畫在關鍵性治療試驗中使用的劑量？預防用藥的劑量又能降低多少？其次，如果最終確定使用這個劑量，鑑於目前的產能，能否請你大致估算一下今年和明年你們可以供應多少種病原體？

Yes. We've modeled the doses and the blood levels from the primate studies in order to design our human studies. And so we are hoping and targeting to achieve similar blood levels in the humans as what we're achieving to achieve the relative efficacies in the primate studies. At those levels, we are at the production level that we could be delivering hundreds of thousands of doses per month for the prophylactic dose level and tens of thousands of doses per month for the treatment levels, assuming they're in those sorts of ranges that we're predicting right now. But of course, all that is all pending the trials and seeing what doses really work. Hopefully, some of the doses work and so forth. So there's still a lot to figure out, but those are the levels that we're targeting and those are the numbers of doses that we're anticipating that we could deliver depending on how all the clinical trials work out.

是的。我們根據靈長類研究中的劑量和血中濃度建立了模型，以此來設計人體試驗。因此，我們希望並力爭在人體試驗中達到與靈長類研究中相似的血中濃度，以達到相應的療效。如果血中濃度達到我們目前預測的水平，那麼在這樣的濃度下，我們每月可以生產數十萬劑預防劑量和數萬劑治療劑量。當然，這一切都取決於試驗結果，以及哪些劑量真正有效。我們希望某些劑量能夠有效等等。所以還有很多問題需要解決，但這些是我們設定的目標濃度和預期的產量，這取決於所有臨床試驗的結果。

Your next question is from the line of Yaron Werber with Cowen.

你的下一個問題來自 Yaron Werber 與 Cowen 的合作系列。

This is Leo Ai for Yaron Werber. Congrats on the side of the quarter and good progress. I just have two questions regarding your COVID-19 program. The first question is regarding the durability and safety of your neutralizing antibodies. It seems that some other antibody developers are kind of modifying the -- actually, demand of their antibody candidates to either extend the half-life or minimize the efficacy [dose-limiting] toxicities. Can you kind of discuss if you made any modifications to your candidates?

我是Leo Ai，代表Yaron Werber。恭喜您本季取得的良好進展。關於您的新冠病毒項目，我有兩個問題。第一個問題是關於您研發的中和抗體的持久性和安全性。似乎其他一些抗體研發公司正在調整其候選抗體的配方——實際上是調整其需求——以延長半衰期或降低劑量限制性毒性。您能否談談您是否對您的候選抗體進行了任何調整？

And my second question is regarding the prevention study. It seems to me that the ongoing Phase III studies looking at preventing infections in household contacts of the infected individual. I'm just wondering because the trial design looks more like postexposure prophylaxis. I'm just wondering if you can provide any details regarding your plans on the prevention trials. Are you looking at like the pre-exposure prophylaxis in other high-risk populations?

我的第二個問題是關於預防研究的。在我看來，目前正在進行的III期研究似乎旨在預防感染者家庭密切接觸者的感染。我之所以有此疑問，是因為該試驗的設計看起來更像是暴露後預防。我想請您提供一些關於預防試驗計劃的細節。您是否也在考慮針對其他高風險族群進行暴露前預防？

Right. Well, there's a lot of questions sort of in there. So one, in terms of engineering our antibodies, historically, we've had very good success with achieving very good half-lives and duration and durability without making modifications, which, as you know, always come with certain risks. So at least for our first-generation antibodies based on that historical success, we're going with unmodified antibodies.

沒錯。這裡面確實包含了很多問題。首先，就抗體工程而言，從歷史經驗來看，我們在不進行任何修飾的情況下，已經能夠獲得非常理想的半衰期、持續時間和耐久性。您也知道，修飾總是伴隨著一定的風險。因此，至少對於我們基於歷史經驗的第一代抗體而言，我們將採用未經修飾的抗體。

In terms of the concerns for antibody-dependent enhancement, we have done extensive studies and efforts on that, including with antibodies that we have or have not modified effector function. And based on all of our data and all of our results, we are going forward with antibodies, once again, that are not modified based on the confidence and the data that we've generated with our preclinical experience.

關於抗體依賴性增強效應的擔憂，我們對此進行了廣泛的研究和努力，包括使用我們已修飾或未修飾效應功能的抗體。基於我們所有的數據和結果，我們決定再次使用未修飾的抗體，這是基於我們臨床前經驗累積的數據和信心。

And finally, what was the last question?

最後一個問題是什麼？

The prevention study.

預防研究。

Oh, the prevention study. Yes. So some of those patients will have already been exposed, but there will be ongoing exposure as well. So it's going to be both a pre- and a postexposure prophylaxis effort. And we will be characterizing whether the patient in the household that we're treating have already been exposed in terms of whether they're already infected or not in our analysis.

哦，預防研究。是的。所以有些患者可能已經接觸過病毒，但也會持續接觸病毒。因此，我們將同時進行暴露前和暴露後預防工作。在我們的分析中，我們會根據患者是否已被感染來判斷是否已經接觸過病毒。

Your next question is from the line of Chris Raymond with Piper Sandler.

你的下一個問題來自克里斯·雷蒙德和派珀·桑德勒的對話。

So just on the EYLEA high-dose program. I know from just looking at the -- from trials.gov website, it looks like your larger DME and AMD trials aren't projected to read out until 2022, but there may be a smaller trial I think, CANDELA, reading out in 2021. So I guess the question here is -- and I know you guys haven't really guided to data yet, but will we get a sense of the feasibility of this approach next year and especially given that this is a higher dose and you got to be mindful of inflammation, et cetera? But also maybe remind us why you guys never went the route of using a half-life extension like a biopolymer.

關於EYLEA高劑量治療項目，我從trials.gov網站上了解到，你們規模較大的DME和AMD試驗預計要到2022年才能公佈結果，但我記得有一個規模較小的試驗，CANDELA，可能會在2021年公佈結果。所以我想問的是──我知道你們還沒公佈具體數據，但我們明年能否了解這種方法的可行性？尤其考慮到這是高劑量方案，需要注意發炎等問題。另外，能否也解釋一下，為什麼你們沒有選擇使用生物聚合物之類的半衰期延長劑？

So I'll take the first part, but George, you can take the latter. In terms of the date for -- we really haven't guided. It depends on -- we're sort of trying to do things in parallel, get some Phase II data while we're enrolling the Phase IIIs. So we'll just have to see how that comes along. And George can comment on the difficulties of biopolymer work.

所以我負責前半部分，喬治，後半部分就交給你了。至於具體日期——我們還沒有給出明確的指導。這取決於－我們正在嘗試並行進行各項工作，在招募三期臨床試驗受試者的同時，也想獲得一些二期臨床試驗的數據。所以我們只能拭目以待了。喬治可以談談生物聚合物研究的困難。

Right. So we have been investing enormously in efforts with biopolymer extension and so forth. And as we all know and has been demonstrated recently with the problems of a major competitor, EYLEA sets a very high bar for safety and for efficacy and particularly from the safety point of view. And in all of our efforts, we have not been satisfied with our biopolymer efforts that those modifications meet that high bar, particularly for safety. And so we have been hesitant to move those programs further into the clinic because of the concerns that we found with those approaches when we compare them and test them in our preclinical settings.

是的。所以我們一直在生物聚合物延伸等方面投入大量資金。眾所周知，最近主要競爭對手安怡（EYLEA）的問題也證明了這一點，安怡對安全性和有效性，尤其是安全性，有著非常高的標準。在我們所有的努力中，我們對生物聚合物的改進並不滿意，這些改進未能達到安怡的高標準，尤其是在安全性方面。因此，由於我們在臨床前研究中發現這些方法存在一些問題，我們一直猶豫是否要將這些項目推進到臨床階段。

In terms of the high-dose EYLEA, we are hoping that we will be able to maintain that safety, that high safety bar with the high-dose EYLEA, but to extend the dosing, as you know, right now, studies show that depending on the patients, about 50% of the patients can go to 2 12 dosing using the current dose of EYLEA. And what we're hoping is that we may be able to increase the percentage of those patients who can go to longer-term dosing using this higher dose, but to achieve that in as safe a manner as we have historically with EYLEA to date. So that's the basis of our strategy.

就高劑量EYLEA而言，我們希望能夠維持其安全性，並維持高劑量EYLEA的高安全標準。如您所知，目前的研究表明，根據患者的具體情況，約50%的患者可以使用目前劑量的EYLEA進行2次12小時的給藥。我們希望能夠提高能夠使用更高劑量進行長期給藥的患者比例，同時確保其安全性與EYLEA以往的安全性保持一致。這就是我們策略的基礎。

Yes. I just might add that we're not sure there's any evidence that there's a dose-dependent effect on inflammation at least with high-quality EYLEA that we make. So I'm not sure that's necessarily going to be the case.

是的。我還要補充一點，我們目前還不確定是否有證據表明，至少就我們生產的高品質EYLEA而言，其對發炎存在劑量依賴性效應。所以我不太確定情況是否一定會如此。

Your next question is from the line of Robyn Karnauskas with Truist.

你的下一個問題來自 Robyn Karnauskas 與 Truist 的對話。

So a question on fasinumab since you announced your top line data this morning. Can you just give us some sense in the hip and the knee? You talk more broadly about the market, but the hip and the knee, what a monthly dose, what the opportunity might be, given that, that would be profile and your strategy for going after now that you know what that profile is going after other joints?

既然您今天早上公佈了法西單抗（fasinumab）的主要數據，我想問一個問題。您能否簡要介紹一下它在髖關節和膝關節方面的應用？您談到了更廣泛的市場情況，但就髖關節和膝關節而言，每月劑量是多少？考慮到這些因素，該藥物的療效特徵是什麼？現在您了解了這些療效特徵，接下來又會如何針對其他關節進行治療？

Well, I think the biggest concern is obviously having to do with the benefit risk and the safety profile. Obviously, there's enormous need for alternatives in the pain field. And there are so many tens of millions of people who are living with osteoarthritis pain with limited options and concerns about all the available medications with all the concerns and problems with opioids, in particular, but also with NSAIDs and so forth, all of these patients are potential candidates for the NGF inhibitors. So we are still awaiting and needing to read out additional safety data from our program. And I think it's going to still be determined in terms of the relative benefit risk as to how important a drug this can be for the so many patients who are in need here.

我認為最大的擔憂顯然在於獲益風險和安全性。顯然，疼痛治療領域對替代療法的需求很大。數以千萬計的骨關節炎患者飽受疼痛折磨，他們可選擇的藥物有限，而且對所有現有藥物都存在擔憂，尤其是阿片類藥物，以及非類固醇抗發炎藥等藥物。所有這些患者都是NGF抑制劑的潛在候選者。因此，我們仍在等待並需要公佈我們專案的更多安全性數據。我認為，最終還是要根據相對獲益風險來判斷這種藥物對於許多急需治療的患者來說究竟有多重要。

Yes. Robyn, I just wanted to mention, glad to see you've got a new name there, Truist sounds good. I don't know if it's the truest. We'd like to think Regeneron is the truest. But at any way, the notion of whether the risk benefit is going to work, as George pointed out, I mean to some extent, we're sort of behind the alliance of Lilly and Pfizer in this class, and they've announced that I think that their action date is in December. They recently said there's not going to be an advisory panel. So we'll get to see as we're preparing our file in collecting that's why they will get to see how the FDA views all this and what constraints or restraints they might put or if they will or they won't approve it. So you'll get a little bit of an insight into the class because it does appear that we see the same kinds of adverse events, in general, in terms of arthropathies and these increased joint replacements that we saw off drug that has been seen with the members of the class.

是的。羅賓，我只是想提一下，很高興看到你們公司有了新名字，Truist聽起來不錯。我不知道它是不是最真實的。我們更傾向於認為Regeneron才是最真實的。但無論如何，風險收益比是否可行，正如喬治指出的那樣，在某種程度上，我們在這個類別中落後於禮來和輝瑞的聯盟，他們已經宣布，我認為他們的審批日期是12月。他們最近表示不會成立諮詢委員會。所以，在我們準備文件收集資料的過程中，我們將有機會了解FDA如何看待這一切，以及他們可能會設定哪些限製或約束，或者他們是否會批准。因此，您將對這類患者有更深入的了解，因為我們似乎看到，就關節病和關節置換手術增加而言，這類不良事件總體上是相同的，而這些不良事件是我們從這類患者服用的藥物中看到的。

Your next question is from the line of Geoff Meacham with Bank of America.

你的下一個問題來自美國銀行的傑夫‧米查姆。

I had one on Libtayo. Obviously, you guys have basal cell and monotherapy in lung as label expansion opportunities. But I just wanted to characterize your -- the trends in 2Q today and maybe your market share is. Do you feel like you're at saturation today? Or is there still an opportunity in your core indication today?

我之前問過Libtayo的問題。顯然，你們在基底細胞癌和肺癌單藥治療方面還有拓展適應症的機會。但我只是想了解你們第二季的發展趨勢，以及你們目前的市佔率。你們覺得現在市場已經飽和了嗎？或者說，在你們的核心適應症領域，現在還有發展空間嗎？

Sure. So this is still relatively early in the launch for Libtayo. The team has done a great job of establishing Libtayo for these patients with locally advanced and metastatic disease with the alternative of Libtayo. But certainly, there's significant opportunity to expand our utilization and, obviously, as you mentioned, as we potentially get into future indications even more for Libtayo.

當然。 Libtayo 目前仍處於上市初期。團隊在推廣 Libtayo 方面做得非常出色，為局部晚期和轉移性疾病患者提供了一種新的治療選擇。當然，Libtayo 的應用還有很大的拓展空間，而且正如您所提到的，隨著我們未來可能探索更多適應症，Libtayo 的應用前景也更加廣闊。

Yes. Obviously, the big indication where most of the sales in this space are is lung cancer, non-small cell lung cancer. And so our exciting data, which will be basis of a filing a monotherapy, and we're moving rapidly towards closing out the final patients enrolled in the chemo combination study. So lung cancer is really the bigger future opportunity if we can successfully complete -- compete there.

是的。顯然，這個領域銷售最大的方向是肺癌，尤其是非小細胞肺癌。我們目前掌握著令人振奮的數據，這些數據將作為我們申請單藥療法的依據。同時，我們也快速推進化療聯合治療研究，爭取完成最後一批患者的入組。因此，如果我們能夠成功完成——在肺癌領域競爭——那麼肺癌將是我們未來更大的機會。

And of course, ultimately, as we tried to highlight, it is a little disappointing how the PD-1 class has not had as dramatic efficacy as one would have want in so many other cancer settings. And that's why we have our very exciting and innovative collection of bispecifics and other combination opportunities that now that we have our own PD-1 as a foundational component, we can now be trying to increase and add efficacy in all of these other cancer settings where right now, the PD-1 class has not really shown as much benefit as one would want, that maybe we can now really create enormous benefit in these settings by making the right combinations, particularly with our bispecifics, but with other combination opportunities as well.

當然，正如我們先前強調的，PD-1 抑制劑在許多其他癌症領域療效未達到預期，這確實令人有些失望。正因如此，我們才擁有了令人振奮且極具創新性的雙特異性抗體及其他聯合療法。如今，我們以自身的 PD-1 抑制劑為基礎，致力於提升 PD-1 抑制劑在其他癌症領域的療效。目前，PD-1 抑制劑在這些領域的療效尚未達到預期，而我們或許能夠透過合理的聯合療法，特別是結合我們的雙特異性抗體以及其他聯合療法，在這些領域創造巨大的益處。

Your next question is from the line of Ronny Gal with Bernstein.

你的下一個問題來自 Ronny Gal 與 Bernstein 的對話。

Congratulations on nice progress. Back to the COVID-19 cocktail, one question I have is about the hospitalization trial, which is how do you monitor against patients mounting the autoimmune response and kind of confounding it that way? And related, does the release of the biomarker data late summer, does that tell us something about the completion of the efficacy readouts? Or is there some relationship there we can follow or maybe in a press release the completion of the enrollment? Just to give us an idea how do we know the antibody efficacy data is coming.

恭喜取得的良好進展。回到新冠病毒聯合療法的話題，我有一個關於住院試驗的問題：如何監測病人自體免疫反應，避免由此造成混淆？另外，生物標記數據在夏末公佈，是否預示療效評估即將完成？或者說，兩者之間是否存在某種關聯，例如，新聞稿中是否會提及病患招募完成？我們只是想了解一下，如何才能確定抗體療效數據即將公佈。

These are all great questions. And in fact, we are analyzing our data exactly with regards to some of the points and concerns that you have. We are measuring -- among the biomarkers, we're measuring patients' endogenous response to their antibody titers. And we're comparing and dividing the patients based on their baseline levels of antibody titers to see whether the patients who respond the best or the people who are not mounting are too early in the course of their disease. And we have this adaptive design. We are going to continue to generate data and evaluate data. We will hopefully be reporting some of that data publicly, but then using that data to make decisions in terms of the adaptive future portions of our design.

這些都是很好的問題。事實上，我們正​​在針對您提出的一些要點和擔憂分析數據。我們正在測量—在眾多生物標記中，我們正在測量患者對自身抗體滴度的內源性反應。我們會根據患者的基線抗體滴度水平進行比較和分組，以觀察反應最佳的患者或抗體滴度未升高的患者是否處於疾病早期階段。我們採用的是這種適應性設計。我們將繼續產生和評估數據。我們希望能夠公開部分數據，並利用這些數據來引導我們設計中未來適應性調整的決策。

Our next question is from the line of Tim Anderson with Wolfe Research.

我們的下一個問題來自 Wolfe Research 的 Tim Anderson。

I have a question on Dupixent and COPD. COPD remains the Holy Grail for asthma biologics, and there have been earlier preliminary COPD data sets with other products that looked good only to fail in Phase III. So I'm wondering if you can put into context the results from the interim look at your COPD trial that you've referenced or at least whether those go, no-go criteria were the same that other biologics have relied on. Or was that interim efficacy bar set higher with Dupixent than with competitor biologics at the same stage of development?

我有一個關於Dupixent和COPD的問題。 COPD一直是氣喘生物製劑的聖杯，先前其他一些產品也曾公佈過COPD的初步數據，這些數據看起來不錯，但最終在III期臨床試驗中失敗了。所以我想請您解釋一下您提到的COPD試驗中期結果，或至少說明一下，您當時的試驗結果是否與其他生物製劑所採用的相同。或者說，Dupixent的中期療效標準是否比處於相同研發階段的競爭對手生物製劑更高？

Yes. I'm not sure that the earlier biologics that you're referring to demonstrated much different data in their Phase II and their Phase III programs. And the problems were -- was that at best, they were demonstrating somewhere around a 15% reduction in their exacerbations. And depending on the Phase III studies, those were on the border of achieving clinical significance, and that's why those programs didn't move forward. So what -- we did not release the details of the bar that we set, but we did say that the bar that we set had to do with exacerbations, and we have to achieve a minimum threshold reduction in exacerbations in order to trigger going forward and triggering the initiation of an additional Phase III. So obviously, the fact that we met a threshold bar for reduction in exacerbations I think creates some excitement that assuming that we can continue to achieve these sorts of reductions in exacerbations that this could be an important drug for COPD.

是的。我不確定您提到的早期生物製劑在第二階段和第三期臨床試驗中是否展現出顯著不同的數據。問題在於──它們充其量只能將急性惡化次數減少約15%。而根據三期臨床試驗的結果，這些結果勉強達到臨床意義的臨界值，這也是這些項目未能繼續進行的原因。所以——我們沒有公佈設定的具體標準，但我們確實說過，我們設定的標準與急性加重次數有關，我們必須達到急性加重次數的最低閾值才能啟動後續的第三期臨床試驗。顯然，我們達到了急性加重次數減少的閾值，我認為這令人振奮，假設我們能夠繼續實現這種程度的急性加重次數減少，那麼這可能是一種治療慢性阻塞性肺病的重要藥物。

Yes. I just want to echo what George said there because this is a little different than most other sort of futility analysis where you say, well, even if you have a slim chance, sometimes you let the trial go forward. As George said, and I'm just really trying to put an exclamation there, it was a stringent. That means it was hard to pass that bar because obviously Sanofi and Regeneron, we didn't want to take on another whole Phase III program, which is -- obviously takes a lot of time, money and effort unless we were told. And we didn't see the data, we just know that we passed this stringent bar, if you will.

是的。我只是想附和喬治剛才說的，因為這跟大多數其他無效性分析略有不同，其他分析通常會說，即使機會渺茫，有時也會讓試驗繼續進行。正如喬治所說，我只是想強調一下，這次的門檻非常高。這意味著要達到這個標準非常困難，因為很顯然，賽諾菲和再生元都不想再啟動另一個完整的三期臨床試驗項目，這顯然需要耗費大量的時間、金錢和精力，除非有人通知我們。而我們當時並沒有看到數據，我們只知道我們通過了這個嚴格的門檻。

And the bar was for reduction in exacerbations.

而衡量標準是減少病情加重次數。

Right.

正確的。

Your next question is from the line of Yatin Suneja with Guggenheim Partners.

你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. A question on the commercial front with regard to the cocktail approach that you have. Can you comment on how do you see this adoption in light of the recent data that we are seeing with vaccine given that they provide a little bit longer protection? Is that the antibody approach has a lower potential to fail versus a vaccine? Or -- and hence, you are almost guaranteed their protection? Maybe perhaps if you can talk about how the market plays out once you have vaccine available.

祝賀你們取得的所有進展。關於你們的雞尾酒療法，我有一個關於商業方面的問題。鑑於疫苗能提供更持久的保護，您能否結合近期疫苗的數據，談談您如何看待這種療法的普及？抗體療法的失敗風險是否低於疫苗？或者說，抗體療法幾乎可以確保提供保護？或許您還能談談疫苗上市後市場的發展？

I wasn't sure whether there was 2 parts of that question, whether there's some insight on the technical aspect. If George understood that, he can certainly answer that. But from the commercial side, I think it's what's been said for a long time. This -- a passive immunization with an antibody cocktail provides immediate immunity. So in the setting of -- and until there's a vaccine, if this comes first, that would be great. But even after there's a vaccine, there'll be many people who are not vaccinated or whose vaccination effects wore off and they got ill or if they were vaccinated, they didn't get enough of a response. So we think there's a lot of places for this passive immunization with an antibody cocktail.

我不確定這個問題是否包含兩個部分，是否涉及一些技術層面的見解。如果喬治理解了這一點，他當然可以回答。但從商業角度來看，我認為大家早就說過——這種使用抗體混合物的被動免疫療法可以提供即時免疫力。因此，在疫苗問世之前，如果這種療法能夠率先奏效，當然也很好。但即使有了疫苗，仍然會有很多人沒有接種疫苗，或者疫苗的效力已經消退導致他們生病，又或者即使接種了疫苗，免疫反應也不夠強烈。所以我們認為這種使用抗體混合物的被動免疫療法有很多應用場景。

George, I'm not sure, was there -- did you follow that other point? Or...

喬治，我不確定，你有沒有註意到──你有沒有註意到那一點？或者…

No. I think that you got it.

不，我覺得你明白了。

Your next question is from the line of Alethia Young with Cantor.

你的下一個問題來自阿萊西亞·楊和坎托爾的傳承。

And I was just kind of curious about what's going on with evinacumab for the ANGPTL3 program. I know that you're filing, but I thought it was a relatively kind of small market opportunity, but just wanted to kind of think about that and what are the potential extension opportunities from there.

我只是有點好奇 ​​evinacumab 在 ANGPTL3 專案上的最新進展。我知道你們正在提交申請，但我認為這是一個相對較小的市場機會，所以我想了解一下，以及未來可能有哪些擴展機會。

Yes. This is ANGPTL3. You said evinacumab. It was a little hard to hear.

是的，這是ANGPTL3。你說的是evinacumab，有點難聽清楚。

Yes. Oh, sorry.

是的。哦，對不起。

Yes. But yes, I think I got it.

是的。不過，我想我明白了。

What are the commercial potential and life beyond that indication as well?

除了上述適應症之外，該藥物的商業潛力和使用壽命如何？

Right. We think this is a very important proof-of-concept setting. These are -- if we get it approved, as you said, it's for homozygous FH, it's for a very rare genetic population. And particularly, what we showed was efficacy in patients who have no LDL receptor function. So that means that this drug and this pathway work totally different than all other drugs that lower lipids and cholesterol. And it may have important growth opportunities after this in the sense that since it is lowering lipids, not only cholesterol, but triglycerides by these independent mechanisms, it is entirely possible, and we are thinking about it, about where there's a broader opportunity eventually for this class of drug. But we're also very excited about the near-term opportunity that we hope we're going to get agreement work from the FDA shortly in the homozygous FH population, particularly those who don't respond to any of the existing drugs.

沒錯。我們認為這是一個非常重要的概念驗證研究。正如您所說，如果獲得批准，它將用於治療純合子家族性高膽固醇血症（FH），這是一個非常罕見的遺傳群體。尤其值得一提的是，我們證實該藥物對低密度脂蛋白受體功能缺失的患者有效。這意味著這種藥物及其作用機制與所有其他降血脂和降膽固醇藥物完全不同。鑑於它不僅能降低膽固醇，還能透過這些獨立的機制降低三酸甘油酯，因此，從某種意義上說，它未來可能具有重要的發展機會。我們正在考慮，這類藥物最終在更廣泛的領域擁有巨大的應用潛力。同時，我們也對近期的機會感到非常興奮，希望能夠盡快獲得FDA的批准，用於治療純合子FH患者，特別是那些對現有藥物無效的患者。

And I'll add just -- you mentioned the size of the population. The -- this is a rare condition. And in the U.S., there's a population of patients, about 1,300 who would be eligible candidates that we feel we'd have an opportunity to help very significantly with this rare and challenging disease. Ex U.S., it's about 1,700.

我還要補充一點——您剛才提到了人口規模。這是一種罕見疾病。在美國，大約有1300名符合條件的患者，我們認為我們有機會為他們提供非常重要的幫助，以對抗這種罕見且棘手的疾病。除美國以外，約有1700名患者。

Your final question will come from the line of Evan Seigerman with Crédit Suisse.

你的最後一個問題將來自瑞士信貸的 Evan Seigerman。

Looking at the antibody data in September, would that be -- assuming it's positive, is that enough to get an EUA from the FDA? And if not, what else do you need to generate and when could we see that data?

根據9月的抗體資料來看，假設結果是陽性，這是否足以獲得FDA的緊急使用授權？如果不夠，還需要產生哪些數據？我們什麼時候能看到這些數據？

Well, it will all depend on the data and how good it looks. So there's so many variables that I think it's really impossible to give a fair answer to that question.

嗯，這完全取決於數據以及數據的品質。變數太多了，我覺得這個問題真的很難給出公正的答案。

Thanks to everybody dialing in. This concludes our call. Bob Landry and the IR team will be available after the call to answer further questions. Stay well and safe, everyone. Thank you very much.

感謝各位撥入電話。本次通話到此結束。鮑勃·蘭德里和投資者關係團隊將在通話結束後繼續解答其他問題。祝大家身體健康，平安健康。非常感謝。

Thank you. This does conclude today's conference call. You may now disconnect.

謝謝。今天的電話會議到此結束，您可以掛斷電話了。