雷傑納榮製藥 (REGN) 2021 Q2 法說會逐字稿

Welcome to the Regeneron Pharmaceuticals Second Quarter 2021 Earnings Conference Call. My name is Tamia, and I will be your operator for today's call. (Operator Instructions) Please note that this conference is being recorded.

歡迎參加 Regeneron Pharmaceuticals 2021 年第二季財報電話會議。我叫塔米婭，我將擔任您今天通話的接線生。（操作員說明）請注意，本次會議正在錄音。

I will now turn the call over to Justin Holko, Vice President, Investor Relations. You may begin.

現在我將把電話交給投資者關係副總裁賈斯汀·霍爾科。你可以開始了。

Thank you, Tamia. 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 2021 Conference Call. An archive of this webcast will be available on our website.

謝謝你，塔米亞。全球各地的聽眾好友們，早安、下午好、晚上好。感謝您對 Regeneron Pharmaceuticals 的關注，歡迎參加 2021 年第二季電話會議。本次網路直播的錄影檔案將會發佈在我們的網站上。

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

今天與我一起參加電話會議的有：創辦人、總裁兼執行長 Leonard Schleifer 博士；共同創辦人、總裁兼首席科學長 George Yancopoulos 博士；執行副總裁兼商業主管 Marion McCourt；以及執行副總裁兼財務長 Bob Landry。在我們發言完畢後，我們將開放問答環節。

I would also like to remind you that 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 business, 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 as well as competition.

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、支付方覆蓋範圍和報銷問題、智慧財產權、未決訴訟和其他程序以及競爭相關的聲明。

Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-Q for the period ended June 30, 2021, which we filed with the SEC earlier today.

每項前瞻性聲明都存在風險和不確定性，可能導致實際結果和事件與該聲明中預測的結果和事件有重大差異。有關這些及其他重大風險的更完整描述，請參閱 Regeneron 向美國證券交易委員會提交的文件，包括我們今天早些時候向美國證券交易委員會提交的截至 2021 年 6 月 30 日的 10-Q 表格。

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

Regeneron不承擔任何更新任何前瞻性聲明的義務，無論是由於新資訊、未來事件或其他原因。

In addition, please note that GAAP and non-GAAP measures will be discussed 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 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, Justin, and thanks to everyone joining today's call. We had an outstanding performance across the enterprise in the second quarter. Not only did our base business performed exceptionally well with strong growth from EYLEA, Dupixent and Libtayo but we also delivered 1.25 million doses of REGEN-COV for the United States government, fulfilling the entire supply contract with BARDA.

謝謝賈斯汀，也謝謝今天參加電話會議的各位。第二季度，我們整個企業都取得了優異的業績。我們的基礎業務不僅表現異常出色，EYLEA、Dupixent 和 Libtayo 實現了強勁增長，而且我們還向美國政府交付了 125 萬劑 REGEN-COV，履行了與 BARDA 的全部供應合約。

We also continue to advance multiple programs across our innovative R&D pipeline with several important readout.

我們也將繼續推動創新研發管線中的多個項目，並取得一些重要的成果。

Starting with EYLEA. Global net sales were over $2.3 billion, growing 33% compared to the prior year, reflecting recovery from the COVID pandemic impact on the second quarter of 2020. In the U.S., sales grew 28%. EYLEA continues to set a high bar in terms of efficacy, safety and convenience.

從愛麗莎開始。全球淨銷售額超過 23 億美元，比上年增長 33%，反映出從 2020 年第二季 COVID-19 疫情的影響中復甦。在美國，銷售額成長了 28%。安禮在功效、安全性和便利性方面持續樹立高標準。

Dupixent also performed exceptionally well this quarter with global sales of $1.5 billion and growth of 59%. This quarter also marks the first time we and Sanofi exceeded $1 billion in U.S. Dupixent quarterly net sales. There remains considerable room for further growth from our in-line indications as well as from potential new opportunities, such as in chronic spontaneous urticaria, or CSU, where last week we announced positive Phase III study results.

Dupixent 本季表現也異常出色，全球銷售額達 15 億美元，成長 59%。本季也是我們和賽諾菲在美國的Dupixent季度淨銷售額首次超過10億美元。我們現有適應症以及潛在的新機會（例如慢性自發性蕁麻疹 (CSU)）仍有相當大的成長空間，上週我們宣布了 CSU 的積極 III 期研究結果。

We have additional Phase III readouts in prurigo nodularis, eosinophilic esophagitis and pediatric atopic dermatitis later this year, which could advance our conviction of Dupixent as a pipeline in a product to address numerous inflammatory diseases.

今年晚些時候，我們將公佈 Dupixent 在結節性癢疹、嗜酸性食道炎和兒童異位性皮膚炎方面的 III 期臨床試驗結果，這可能會增強我們對 Dupixent 作為治療多種發炎性疾病的產品線的信心。

In oncology, Libtayo global net sales were $117 million and grew 46% with meaningful growth contributions from both inside and outside the United States. We also announced this morning that in a large Phase III pivotal study in non-small cell lung cancer, Libtayo, combined with standard chemotherapy, reduced the risk of death by nearly 30% compared to chemotherapy alone. We are eager to share these data with regulatory agencies, which, if approved, would dramatically increase the number of lung cancer eligible patients who could be treated with Libtayo.

在腫瘤領域，Libtayo 的全球淨銷售額為 1.17 億美元，成長了 46%，其中美國境內外均有顯著成長貢獻。今天早上我們也宣布，在一項針對非小細胞肺癌的大型 III 期關鍵性研究中，Libtayo 與標準化療聯合使用，與單獨化療相比，死亡風險降低了近 30%。我們渴望與監管機構分享這些數據，如果獲得批准，將大大增加符合條件的肺癌患者數量，這些患者可以使用 Libtayo 進行治療。

We also began to see meaningful results from our Regeneron Genetics Medicines pipeline. With our collaborators at Intellia, we showed the first ever proof-of-concept in vivo genome editing with NTLA-2001, investigational CRISPR therapy for transthyretin amyloidosis, or ATTR amyloidosis. This proof-of-concept study utilizing systemically administered CRISPR technology for genome modification suggests this approach could have broad applicability across a wide range of diseases.

我們也開始看到 Regeneron Genetics 藥物研發管線有顯著成果。我們與 Intellia 的合作者一起，首次展示了 NTLA-2001（一種用於治療轉甲狀腺素蛋白澱粉樣變性或 ATTR 澱粉樣變性的在研 CRISPR 療法）在體內進行基因組編輯的概念驗證。這項利用系統性 CRISPR 技術進行基因組修改的概念驗證研究表明，這種方法可能對多種疾病具有廣泛的適用性。

Beyond Intellia, our collaborations with Alnylam and Decibel are helping to form a whole new pipeline for next-generation therapies beyond our broad and diverse antibody pipeline.

除了 Intellia 之外，我們與 Alnylam 和 Decibel 的合作正在幫助我們建立一個全新的下一代療法產品線，超越我們廣泛而多樣化的抗體產品線。

The second quarter represented another landmark in our efforts to combat COVID-19, which unfortunately, despite considerable rates of vaccination, continues to be a major global health concern with rising cases and emerging variants. In addition to fulfilling our entire supply contract with the United States government, we were able to secure Emergency Use Authorization updates for our lower 1.2-gram subcutaneous dose as well as for post-exposure prophylaxis for certain appropriate patients who are at high risk for disease. Utilization is increasing rapidly at currently more than 50,000 doses ordered per week.

第二季度是我們對抗 COVID-19 努力中的又一個里程碑。不幸的是，儘管疫苗接種率很高，但 COVID-19 仍然是一個主要的全球健康問題，病例不斷增加，變種病毒不斷出現。除了履行與美國政府的全部供應合約外，我們還獲得了較低劑量（1.2 克）皮下注射劑的緊急使用授權更新，以及針對某些患病風險較高的合適患者的暴露後預防的緊急使用授權更新。目前疫苗使用量正在迅速增加，每週訂購劑量超過 5 萬劑。

We also announced that the U.K. RECOVERY study showed a 20% reduction in risk of death in hospitalized patients who had not mounted their own immune response.

我們也宣布，英國 RECOVERY 研究表明，對於沒有產生自體免疫反應的住院患者，死亡風險降低了 20%。

With these results, together with supporting data from Regeneron study in hospitalized patients that George will discuss momentarily, REGEN-COV has the potential, if so authorized, to be the first treatment to be used in a wide spectrum of COVID-19 disease settings from prevention through the hospitalized setting.

結合這些結果，以及喬治稍後將要討論的來自 Regeneron 對住院患者的研究的支持數據，如果獲得批准，REGEN-COV 有可能成為第一個用於 COVID-19 疾病各個階段（從預防到住院治療）的治療方法。

In summary, our core business is strong and continues to diversify, and our innovative pipeline continues to advance, positioning Regeneron well for long-term growth.

總而言之，我們的核心業務實力雄厚，並不斷實現多元化發展，我們的創新產品線也在不斷推進，這使得 Regeneron 能夠更好地實現長期成長。

Now I will turn the call over to George.

現在我將把電話交給喬治。

Thank you, Len. We have a lot to talk about this morning, which is all possible because of our Regeneron colleagues who have been working nonstop throughout this pandemic. And unfortunately, the world is still in the throes of this global COVID-19 pandemic as the numbers of infected individuals in the United States are climbing again with nearly 100,000 Americans becoming infected every day. Therefore, I will start with Regeneron -- with REGEN-COV, our monoclonal antibody cocktail for COVID-19.

謝謝你，Len。今天早上我們有很多事情要談，這都要感謝 Regeneron 的同事們，他們在整個疫情期間一直不間斷地工作。不幸的是，世界仍深陷新冠肺炎全球大流行之中，美國的感染人數再次攀升，每天有近 10 萬美國人感染。因此，我將首先介紹 Regeneron 公司——以及我們用於治療 COVID-19 的單株抗體雞尾酒療法 REGEN-COV。

In June, the REGEN-COV Emergency Use Authorization, or EUA, was updated to include the lower 1.2-gram REGEN-COV dose with both intravenous and subcutaneous administration for nonhospitalized patients. This EUA was supported by Phase III data showing that the 1.2-gram dose reduced risk of hospitalization or death by 70%. Just last week, the EUA was further expanded to include utilization in post-exposure prophylaxis for COVID-19 in certain populations, and also allows for repeated monthly dosing of REGEN-COV for high-risk patients, such as the immunocompromised who are at high risk of ongoing exposure to infected individuals in the same institutional setting.

6 月，REGEN-COV 緊急使用授權 (EUA) 進行了更新，將較低的 1.2 克 REGEN-COV 劑量納入其中，可用於非住院患者的靜脈注射和皮下注射。此緊急使用授權得到了 III 期臨床試驗數據的支持，數據顯示 1.2 克劑量可將住院或死亡風險降低 70%。就在上週，緊急使用授權進一步擴大，將用於某些人群的 COVID-19 暴露後預防，並允許對高風險患者（例如免疫功能低下、在同一機構環境中持續接觸感染者風險較高的患者）每月重複注射 REGEN-COV。

This latest authorization makes REGEN-COV the only treatment that is available for both treating infected individuals and also preventing infection in certain settings. We would like to emphasize that REGEN-COV is not a substitute for vaccination.

此次最新授權使 REGEN-COV 成為唯一一種既可用於治療感染者，又可用於在特定情況下預防感染的治療方法。我們想強調的是，REGEN-COV 不能取代疫苗接種。

Still under review by the FDA, our additional data, which we believe could broaden the prevention application to pre-exposure prophylaxis as well as to extend the treatment paradigm to hospitalized patients. The details of Part A of our Phase III prophylaxis study in which we assessed efficacy and safety of subcutaneous REGEN-COV in preventing infection among previously uninfected individuals has just been published today in the New England Journal of Medicine.

我們的補充數據仍在接受 FDA 的審查，我們相信這些數據可以擴大預防應用範圍，使其適用於暴露前預防，並可將治療模式擴展到住院患者。今天，《新英格蘭醫學雜誌》剛剛發表了我們 III 期預防研究 A 部分的詳細信息，該研究評估了皮下注射 REGEN-COV 在預防先前未感染個體感染方面的療效和安全性。

We believe there is enormous unmet need to try to protect immunocompromised individuals who have not responded to the vaccine and we hope that the FDA will agree that our data will support an authorization in this pre-exposure prophylaxis setting.

我們認為，對於免疫功能低下、對疫苗沒有反應的個體，存在著巨大的未滿足需求，我們希望 FDA 能夠同意我們的數據將支持在這種暴露前預防情況下給予授權。

For hospitalized patients, we recently reported that REGEN-COV, tested as part of the Oxford University Phase III RECOVERY study, met its primary outcome, reducing risk of death by 20% in hospitalized COVID-19 patients lacking immune response to SARS-CoV-2. Data from our own smaller study in hospitalized COVID-19 patients showed similar conclusions with 35% reduction in overall mortality in this study, which was limited to earlier-stage hospitalized patients with no oxygen or low oxygen support. These collective data from RECOVERY and from our study in hospitalized patients have been shared with regulators.

對於住院患者，我們最近報告稱，作為牛津大學 III 期 RECOVERY 研究的一部分進行測試的 REGEN-COV 達到了其主要結果，使缺乏對 SARS-CoV-2 免疫反應的 COVID-19 住院患者的死亡風險降低了 20%。我們自己對住院 COVID-19 患者進行的一項規模較小的研究的數據也得出了類似的結論，該研究的總體死亡率降低了 35%，但僅限於早期住院且沒有氧氣或氧氣支持不足的患者。RECOVERY 計畫和我們對住院患者的研究的這些總結數據已與監管機構共享。

In addition, we are on track to complete the REGEN-COV BLA submissions in the second half of 2021.

此外，我們預計在 2021 年下半年完成 REGEN-COV BLA 的提交。

Outside of the United States, our collaborator Roche obtained emergency or temporary pandemic use authorizations for our COVID-19 antibody cocktail, known as Ronapreve outside the United States in more than 20 countries across the European Union, India, Switzerland and Canada, with more authorizations expected soon. Japan was the first country to grant formal regulatory approval to our antibody cocktail for COVID-19.

在美國以外，我們的合作夥伴羅氏已在歐盟、印度、瑞士和加拿大等 20 多個國家/地區獲得了我們 COVID-19 抗體雞尾酒療法（在美國以外被稱為 Ronapreve）的緊急或臨時疫情使用授權，預計很快將獲得更多授權。日本是第一個正式批准我們研發的用於治療新冠肺炎的抗體雞尾酒療法的國家。

Finally, REGEN-COV retains potent activity against all known variants of interest, including the Delta variant. For patients at high risk of serious consequences, including many with an inadequate response to vaccines, REGEN-COV could be an important option to patients and their physicians for the foreseeable future.

最後，REGEN-COV 對所有已知的目標變異株（包括 Delta 變異株）仍具有強大的活性。對於有嚴重後果高風險的患者，包括許多對疫苗反應不足的患者，在可預見的未來，REGEN-COV 可能是患者及其醫生的重要選擇。

Moving on to ophthalmology. In the coming months, we expect data from the Phase II study of high dose aflibercept in wet AMD. This readout will consist of efficacy assessments on drawing in other anatomical measures as well as safety on the 8-milligram and the currently approved 2-milligram aflibercept dose at an 8-week dosing interval.

接下來是眼科學。在接下來的幾個月裡，我們期待獲得高劑量阿柏西普治療濕性老年黃斑部病變 (AMD) II 期研究的數據。本次讀數將包括對其他解剖學測量指標的療效評估，以及對 8 毫克和目前已批准的 2 毫克阿柏西普劑量在 8 週給藥間隔下的安全性評估。

In the 106 patients dosed in the open-label Phase II to date, we have not seen any concerning safety signals. While this smaller study will not be definitive on durability measures, the Phase II data will help provide insights into the larger Phase III studies, which are testing high-dose aflibercept dosing intervals out to 12 and 16 weeks. I'm pleased to announce that the Phase III studies in DME and AMD have completed enrollment, allowing for Phase III data next year.

在迄今為止的開放標籤 II 期試驗中，106 名患者接受了給藥，我們沒有發現任何令人擔憂的安全訊號。雖然這項規模較小的研究無法對持久性指標做出最終決定，但 II 期數據將有助於深入了解更大規模的 III 期研究，這些研究正在測試高劑量阿柏西普給藥間隔長達 12 週和 16 週。我很高興地宣布，DME 和 AMD 的 III 期研究已完成入組，明年將公佈 III 期數據。

Moving on to Dupixent in our immunology and inflammation portfolio. Just last week, we announced that a Phase III trial in chronic spontaneous urticaria, or CSU, met primary and all key 24-week secondary endpoints, showing Dupixent reduced itch and hive activity scores by nearly half. This is the fifth disease in which Dupixent demonstrated positive pivotal trial results, and efficacy in this disease raises the possibility that IL-4 and IL-13 are critical drivers in diseases not traditionally thought to be driven by type 2 inflammation.

接下來介紹我們免疫學和發炎產品組合中的Dupixent。就在上週，我們宣布，一項針對慢性自發性蕁麻疹（CSU）的 III 期試驗達到了主要終點和所有關鍵的 24 週次要終點，結果顯示 Dupixent 將瘙癢和蕁麻疹活動評分降低了近一半。這是 Dupixent 在第五種疾病中取得積極的關鍵性試驗結果，而其在該疾病中的療效表明，IL-4 和 IL-13 可能是某些疾病的關鍵驅動因素，而這些疾病通常不被認為是由 2 型發炎驅動的。

We plan to report results from a second trial in CSU patients who are not benefiting from the approved standard of care biologic in early 2022. This positive readout in CSU is continuing to build on Dupixent's efficacy and safety demonstrated across other inflammatory diseases. In the upcoming months, we also expect results from our confirmatory Phase IIIb study in adult and adolescent patients with eosinophilic esophagitis as well as readout of a Phase III study in prurigo nodularis. Thus far, Dupixent is approved in patients as young as 6 years old in atopic dermatitis and 12 years old in asthma.

我們計劃在 2022 年初公佈針對未從已批准的標準生物製劑治療中獲益的 CSU 患者的第二次試驗結果。CSU 的正面結果進一步鞏固了 Dupixent 在其他發炎性疾病中展現的療效和安全性。在接下來的幾個月裡，我們也將發表針對成人和青少年嗜酸性食道炎患者的確證性 IIIb 期研究結果，以及針對結節性癢疹的 III 期研究結果。目前，Dupixent 已獲準用於治療 6 歲及以上的異位性皮膚炎患者和 12 歲及以上的氣喘患者。

Later this year, we will report data from a Phase III study in preschool children as young as 6 months up to 5 years of age suffering from atopic dermatitis. In asthma, we anticipate a regulatory decision in October for children aged 6 to 11 years old in the United States.

今年晚些時候，我們將公佈一項針對 6 個月至 5 歲患有異位性皮膚炎的學齡前兒童的 III 期研究數據。對於氣喘，我們預計美國將於 10 月對 6 至 11 歲兒童做出監管決定。

Moving to our anti-interleukin-33 antibody, itepekimab. Results of the Phase II study in COPD patients were recently published in Lancet Respiratory Medicine. While the trial exhibited strong trends in its primary endpoint of exacerbation reduction in the overall population, which did not meet statistical significance, a pre-specified subgroup analysis of former smokers with COPD is what accounted for the overall benefit with no negative subset in the remaining population. In the pre-specified former smoker subgroup, itepekimab demonstrated a 42% reduction in exacerbations and improvement in lung function of 0.09 liters compared to placebo with both endpoints reaching nominal statistical significance.

接下來是我們的抗白細胞介素-33抗體，itepekimab。針對慢性阻塞性肺病患者的 II 期研究結果最近發表在《刺胳針呼吸醫學》雜誌上。雖然該試驗在總體人群中主要終點（即病情加重減少）方面顯示出強勁的趨勢，但並未達到統計學意義，而預先設定的針對患有 COPD 的前吸煙者的亞組分析解釋了總體獲益，其餘人群中沒有出現負面亞組。在預先指定的戒菸者亞組中，與安慰劑相比，itepekimab 使病情加重減少了 42%，肺功能提高了 0.09 公升，這兩個終點均達到了名義上的統計意義。

Moreover, the publication includes genetic analyses that support a protective role for interleukin-33 in COPD. Based on these results, we and Sanofi are assessing the potential of itepekimab in 2 Phase III studies focused on the former smoker population with COPD. I should also remind you that we have 2 ongoing studies with phase -- 2 ongoing Phase III studies with Dupixent in a complementary COPD population.

此外，該出版物還包括基因分析，支持白細胞介素-33在慢性阻塞性肺病中發揮保護作用。基於這些結果，我們和賽諾菲正在評估itepekimab在兩項針對患有COPD的前吸菸人群的III期研究中的潛力。我還應該提醒您，我們目前有 2 項正在進行的 III 期研究，針對的是 Dupixent 在 COPD 互補人群中的應用。

We are also progressing our novel approaches to treat allergies by using cocktails of monoclonal antibodies to directly bind and inactivate allergens, which have produced robust results in Phase II studies. Results of the initial Phase III study of our antibody cocktail against birch allergy caused by the Bet v 1 allergen are expected later this year. The first Phase III study of an antibody cocktail for cat allergy caused by Fel d 1 allergen is now open for enrollment. We are enthusiastic about these innovative additions to our inflammation and immunology portfolio.

我們也在推進治療過敏症的新方法，即使用單株抗體混合物直接結合併滅活過敏原，這種方法在 II 期研究中取得了顯著成果。針對 Bet v 1 過敏原引起的樺樹過敏的抗體混合物的初步 III 期研究結果預計將於今年稍後公佈。首個針對 Fel d 1 過敏原引起的貓過敏的抗體雞尾酒療法 III 期研究現已開始招募患者。我們非常高興能將這些創新產品添加到我們的發炎和免疫學產品組合中。

In oncology, following its recent approvals in the United States for certain first-line non-small cell lung cancer in certain advanced basal cell carcinoma patients, Libtayo was subsequently approved in the EU for these settings. Furthermore, compelling overall survival data in second-line cervical cancer patients were presented at an ESMO Virtual Plenary in May with the regulatory submissions to the FDA and EMA planned for this year.

在腫瘤學領域，繼最近在美國獲準用於治療某些晚期基底細胞癌患者的某些一線非小細胞肺癌後，Libtayo 隨後在歐盟獲準用於這些適應症。此外，在 5 月舉行的 ESMO 虛擬全體會議上，公佈了二線子宮頸癌患者的令人信服的總生存期數據，併計劃於今年向 FDA 和 EMA 提交監管申請。

For lung cancer, we are pleased to report today that in our Phase III trial comparing Libtayo plus standard chemotherapy versus chemotherapy alone, the independent data monitoring committee recommended halting the trial for efficacy at the second interim analysis. Libtayo plus chemotherapy significantly improved overall survival as well as progression-free survival compared to chemotherapy alone in first-line locally advanced or metastatic non-small cell lung cancer.

對於肺癌，我們今天很高興地報告，在我們比較 Libtayo 加標準化療與單獨化療的 III 期試驗中，獨立數據監測委員會在第二次中期分析中建議因療效而停止試驗。與第一線局部晚期或轉移性非小細胞肺癌患者單獨接受化療相比，Libtayo合併化療顯著提高了總存活期和無惡化存活期。

With these data, Libtayo is now the second PD-1 targeting antibody that has been able to demonstrate significant overall survival benefit both as a monotherapy as well as in combination with chemotherapy for treating advanced lung cancer. With this validation, Libtayo provides an important foundation for a broad and multifaceted approach to address the great unmet need that patients with cancer in general and lung cancer, in particular, still face.

根據這些數據，Libtayo 現在是第二種能夠證明在治療晚期肺癌方面，無論是作為單藥療法還是與化療聯合使用，都能顯著提高總生存期的 PD-1 靶向抗體。有了這項驗證，Libtayo 為採取廣泛而多方面的方法來解決癌症患者（尤其是肺癌患者）仍然面臨的巨大未滿足需求奠定了重要的基礎。

In addition to our Libtayo monotherapy and chemo combination opportunities in lung cancer, we are developing several bispecifics. Our EGFRxCD28 co-stim and Libtayo combination is in dose escalation for lung and other advanced cancers. Our MET X MET bispecific antibody is enrolling non-small cell lung cancer patients with a broad selection of patients, including MET Exon 14 gene mutation, gene amplification and/or elevated MET protein expression.

除了我們在肺癌治療中提供的 Libtayo 單藥療法和化療聯合療法之外，我們還在開發幾種雙特異性抗體。我們正在對 EGFRxCD28 共刺激劑和 Libtayo 組合進行劑量遞增試驗，用於治療肺癌和其他晚期癌症。我們的 MET X MET 雙特異性抗體正在招募非小細胞肺癌患者，患者選擇範圍廣泛，包括 MET 外顯子 14 基因突變、基因擴增和/或 MET 蛋白表達增加。

And as we introduced at our ASCO investor event, our first antibody drug conjugate, MET X MET ADC, is poised to enter the clinic in the coming months with a focus on patients with MET Overexpressing cancers, including lung cancer, where MET Overexpression occurs in as many as 25% of patients.

正如我們在 ASCO 投資者活動上介紹的那樣，我們的首個抗體藥物偶聯物 MET X MET ADC 將在未來幾個月內進入臨床階段，重點治療 MET 過度表現的癌症患者，包括肺癌患者，其中高達 25% 的患者存在 MET 過度表現。

In terms of building on the potential of Libtayo with combinations in skin cancer, we recently announced new clinical data for the combination of Libtayo with fianlimab, our LAG-3 inhibitor, in advanced melanoma at the ASCO annual meeting in June. The combination demonstrated a 67% response rate in PD-1 or PD-L1 naive patients with potential for a more favorable safety profile than with the anti-CTLA-4 PD-1 combinations. We plan to initiate a Phase III study of fianlimab and Libtayo as a first-line treatment for advanced melanoma in 2022.

為了進一步發揮 Libtayo 在皮膚癌治療中的聯合用藥潛力，我們最近在 6 月的 ASCO 年會上公佈了 Libtayo 與我們的 LAG-3 抑制劑 fianlimab 聯合治療晚期黑色素瘤的新臨床數據。此聯合療法在 PD-1 或​​ PD-L1 初治患者中顯示出 67% 的反應率，並且與抗 CTLA-4 PD-1 聯合療法相比，具有更好的安全性。我們計劃於 2022 年啟動 fianlimab 和 Libtayo 作為晚期黑色素瘤一線治療的 III 期研究。

Ovarian cancer is the first tumor type for which we are clinically testing 3 powerful combination approaches. First, our MUC16xCD3 bispecific with Libtayo, where we hope to share initial data next year. Next, our MUC16xCD28 co-stim bispecific with Libtayo. And third, our novel combination of the CD3 and co-stim bispecifics for which we have now dosed the first patient.

卵巢癌是我們正在進行臨床試驗，測試三種強效聯合療法的首個腫瘤類型。首先，我們與Libtayo合作開發了MUC16xCD3雙特異性抗體，我們希望明年能分享初步數據。接下來，我們將使用 Libtayo 開發我們的 MUC16xCD28 共刺激雙特異性抗體。第三，我們研發了一種新型的 CD3 和共刺激雙特異性抗體組合，目前我們已經對第一位患者進行了給藥。

This latter combination of 2 bispecifics of 2 different classes has potential to be a novel and disruptive approach for the treatment of solid tumors. Rounding out my commentary in solid tumors, our PSMAxCD28 program in prostate cancer continues in dose escalation with Libtayo, and we hope to share initial data next year.

後者將兩種不同類別的雙特異性抗體組合在一起的方法，有可能成為治療實體腫瘤的一種新穎且顛覆性的方法。最後，關於實體瘤的評論，我們的 PSMAxCD28 前列腺癌計畫正在使用 Libtayo 進行劑量遞增試驗，我們希望明年分享初步數據。

As we mentioned previously, we are planning on introducing a PSMAxCD3 bispecific to the clinic later this year, providing another unique experimental combination for prostate cancer treatment. The tumor viewed as nonresponsive currently to available immunotherapies.

正如我們之前提到的，我們計劃在今年稍後將 PSMAxCD3 雙特異性抗體引入臨床，為前列腺癌治療提供另一種獨特的實驗性組合。該腫瘤目前被認為對現有的免疫療法沒有反應。

Moving on to hematologic cancers, and starting with lymphoma. Odronextamab, our CD20xCD3 bispecific, has demonstrated encouraging efficacy and durability of responses in hard-to-treat patient populations. We have resumed enrollment in our potentially pivotal Phase II program in follicular lymphoma and diffuse large B-cell lymphoma, with lifting of the partial clinical hold following protocol amendments for a modified step-up dosing protocol.

接下來討論血液腫瘤，首先是淋巴瘤。我們的 CD20xCD3 雙特異性抗體 Odronextamab 在難治性患者族群中展現出令人鼓舞的療效和持久的療效。我們已恢復了針對濾泡性淋巴瘤和瀰漫性大B細胞淋巴瘤的潛在關鍵性 II 期項目的招募工作，此前由於方案修改為改良的遞增劑量方案，部分臨床暫停已被解除。

Later this year, we plan to initiate testing of the odronextamab subcutaneous formulation. And next year, we plan to initiate the Phase III program as well as combination trials with our lymphoma-specific co-stim bispecific.

今年晚些時候，我們計劃啟動 odronextamab 皮下製劑的測試。明年，我們計劃啟動 III 期臨床試驗項目，以及與我們的淋巴瘤特異性共刺激雙特異性抗體的聯合試驗。

In multiple myeloma, our BCMAxCD3 bispecific is on track to complete enrollment in a potentially pivotal Phase II study next year. We will also initiate studies evaluating a subcutaneous formulation in combinations with standard of care.

在多發性骨髓瘤領域，我們的 BCMAxCD3 雙特異性抗體預計將在明年完成一項可能具有關鍵意義的 II 期研究的患者招募。我們也將啟動研究，評估皮下製劑與標準療法的聯合應用。

With our unique position to mix and match multiple modalities and targets with the goal of deepening the responses we are already observing with our BCMAxCD3 bispecific, we are on track to start a combination study with a co-stim bispecific for multiple myeloma next year.

憑藉我們獨特的優勢，我們可以將多種療法和標靶進行混合搭配，以期加深我們對 BCMAxCD3 雙特異性抗體的觀察結果，我們預計明年啟動一項針對多發性骨髓瘤的共刺激雙特異性抗體聯合治療研究。

I would like to conclude with our Regeneron Genetics Medicines efforts. As you know, these efforts start with our Regeneron Genetics Center and its ability to genetically identify and validate new disease targets and is coupled with emerging gene-based therapeutic solutions to address these targets, including CRISPR-based technologies with our collaborator Intellia, siRNA technologies with Alnylam as well as viral gene delivery technologies we are developing in-house.

最後，我想談談我們在 Regeneron Genetics Medicines 所做的努力。如您所知，這些努力始於我們的 Regeneron 遺傳學中心，該中心能夠透過基因手段識別和驗證新的疾病靶點，並結合新興的基於基因的治療解決方案來解決這些靶點，包括與我們的合作夥伴 Intellia 合作的基於 CRISPR 的技術、與 Alnylam 合作的 siRNA 技術以及我們正在內部開發的病毒基因遞送技術。

The Regeneron Genetics Center continues to emerge as a world leader in human sequencing and in defining genetic variants that can either be protective or causative for human disease, most recently identifying a major new gene target that protects against obesity as described in a high-profile publication in Science last month. For this newly discovered target, we are deploying several strategies to develop new classes of potential therapeutics to fight obesity and potentially type 2 diabetes.

再生元遺傳學中心持續成為人類定序領域的全球領導者，並致力於定義對人類疾病具有保護作用或致病作用的基因變異。最近，該中心發現了一個新的重要基因靶點，可以預防肥胖，相關研究成果已在上個月發表於《科學》雜誌的一篇高規格文章中進行了描述。針對這項新發現的目標，我們正在採取多種策略來開發新型潛在療法，以對抗肥胖症，並有可能對抗第 2 型糖尿病。

In terms of progress with our gene-based therapeutics approaches, together with the Intellia, we recently announced positive clinical data for the first ever systemically delivered CRISPR-based gene knockout in human patients.

在基因治療方法方面，我們與 Intellia 合作，最近公佈了首次在人類患者中進行全身性 CRISPR 基因敲除的積極臨床數據。

In the first 6 patients with transthyretin amyloidosis, or TTR amyloidosis, a single systemic treatment led to dose-dependent reduction in the disease-causing protein with no serious adverse events observed through day 28. This proof-of-concept clinical data increases the probability of success for both our knockout as well as our Insertion CRISPR-based programs, unlocking the potential of many future possibilities for Intellia and Regeneron.

在前 6 名患有轉甲狀腺素蛋白澱粉樣變性（TTR 澱粉樣變性）的患者中，單次全身性治療導致致病蛋白劑量依賴性減少，且在第 28 天未觀察到嚴重不良事件。這項概念驗證的臨床數據提高了我們基因敲除和基因插入 CRISPR 計畫的成功機率，為 Intellia 和 Regeneron 開啟了許多未來的可能性。

Currently, we're evaluating more than 20 preclinical programs under this collaboration, and Regeneron has the rights to develop up to 15 in vivo products with Intellia.

目前，我們正在評估該合作下的 20 多個臨床前項目，Regeneron 擁有與 Intellia 合作開發多達 15 種體內產品的權利。

Regarding our efforts with Alnylam, on an siRNA for a novel NASH target identified by the Regeneron Genetics Center, we are hoping to see initial healthy volunteer data by the end of this year. This 2-part first-in-human study is now enrolling NASH patients. We are currently evaluating about 20 preclinical programs under this collaboration, and Regeneron has rights to develop up to 30 products with Alnylam.

關於我們與 Alnylam 合作，針對 Regeneron Genetics Center 發現的新型 NASH 標靶的 siRNA 的研究，我們希望在今年年底前看到初步的健康志願者數據。這項分為兩部分的首次人體試驗目前正在招募 NASH 患者。我們目前正在評估該合作下的約 20 個臨床前項目，Regeneron 擁有與 Alnylam 共同開發多達 30 種產品的權利。

With that brief glimpse into the future of Genetics Medicines, I would like to turn the call over to Marion.

在簡要地了解了基因藥物的未來之後，我想把電話交給瑪莉安。

Thank you, George. Our business performance in the second quarter reflects robust momentum, competitive strength and focused execution across our commercial portfolio.

謝謝你，喬治。第二季的業務表現反映了我們商業組合的強勁成長動能、競爭優勢和專注執行力。

Our in-line medicines continue to thrive, and our ongoing launches are progressing to plan, providing a platform for diversified growth.

我們的在研藥物持續蓬勃發展，我們正在進行的上市計劃也按計劃進行，為多元化成長提供了平台。

First, I will highlight our efforts supporting REGEN-COV, our COVID-19 antibody cocktail, which is available under Emergency Use Authorization by the FDA. In the second quarter, U.S. net sales were $2.6 billion as a result of fulfilling our second contract with the U.S. government. There is significant ongoing need for effective treatments against COVID-19. As Len said, REGEN-COV utilization has recently accelerated and is now trending well over 50,000 doses ordered weekly. Uptake is driven by growing recognition of the importance of antibody cocktail treatment, focused educational efforts and competitive dynamics favoring REGEN-COV. We continue to work closely with all key stakeholders to increase REGEN-COV utilization and support hospitals and administration sites to reduce bottlenecks.

首先，我將重點介紹我們為支持 REGEN-COV（我們的 COVID-19 抗體雞尾酒療法）所做的努力，該療法已獲得 FDA 的緊急使用授權。第二季度，由於履行了與美國政府的第二份合同，美國淨銷售額達到 26 億美元。目前對有效治療新冠肺炎的方法仍有巨大的需求。正如 Len 所說，REGEN-COV 的使用量最近有所加快，目前每週訂購量已超過 5 萬劑。抗體雞尾酒療法的重要性日益被認識，教育工作重點開展，以及有利於 REGEN-COV 的競爭態勢推動了該產品的普及。我們將繼續與所有主要利益相關者密切合作，以提高 REGEN-COV 的使用率，並支持醫院和行政機構減少瓶頸。

The REGEN-COV antibody cocktail is both FDA authorized and NIH recommended and retains potency against known variants. We've also expanded our efforts following the recent post-exposure prophylaxis authorization, the first for an antibody therapy in this setting.

REGEN-COV 抗體混合物已獲得 FDA 批准和 NIH 推薦，並且對已知變異株仍具有效力。繼最近獲得暴露後預防授權（這是該領域首個抗體療法授權）之後，我們也擴大了工作範圍。

Beyond REGEN-COV, our core portfolio performed very well in the second quarter. Starting with EYLEA. Second quarter global net sales grew 33% year-over-year to over $2.3 billion. In the U.S., EYLEA net sales grew 28% year-over-year to $1.42 billion driven by underlying demand, category share gains and a favorable comparison versus the second quarter of 2020. EYLEA is the anti-VEGF category growth leader and preferred treatment option.

除了 REGEN-COV 之外，我們的核心投資組合在第二季表現非常出色。從愛麗莎開始。第二季全球淨銷售額年增 33%，超過 23 億美元。在美國，安怡淨銷售額年增 28% 至 14.2 億美元，這得益於潛在需求、品類份額增長以及與 2020 年第二季度相比的有利基數。EYLEA 是抗 VEGF 藥物領域的成長領導者和首選治療方案。

As a reminder, EYLEA sets a high bar for efficacy and safety with more than 40 million injections administered worldwide, in a therapeutic category where patient vision and well-being are paramount. EYLEA continues to capture market and competitive share, securing nearly 50% of the overall category and 75% of the branded category.

需要提醒的是，EYLEA 在療效和安全性方面樹立了很高的標準，全球已註射超過 4000 萬劑，而在這個治療領域，患者的視力和健康至關重要。安樂持續擴大市場份額和競爭份額，佔據了整個品類近 50% 的份額和品牌品類 75% 的份額。

Overall demand is improving with increased patient flow and return to pre-pandemic levels of new patient visits. Patients who may have delayed seeing the retina specialists are now seeking treatment.

整體需求正在改善，患者就診量增加，新患者就診量恢復到疫情前水準。一些之前可能耽誤了就診視網膜專科醫生的患者現在正在尋求治療。

With this backdrop, we are accelerating promotional efforts to address the significant unmet needs in diabetic eye disease. We are confident in Regeneron's ongoing leadership position in retinal diseases based on EYLEA's competitive advantages and future opportunities, including our high-dose program.

在此背景下，我們正在加速宣傳工作，以滿足糖尿病眼疾領域尚未滿足的重大需求。我們對 Regeneron 在視網膜疾病領域持續保持領先地位充滿信心，這得益於 EYLEA 的競爭優勢和未來機遇，包括我們的高劑量治療方案。

Turning to Libtayo, where second quarter global net sales grew to $117 million and the U.S. net sales grew 23% to $78 million. As expected, at this early stage of new indication launches, the vast majority of sales come from advanced cutaneous squamous cell carcinoma, where Libtayo is the #1 systemic treatment despite new in-class competition.

再來看看 Libtayo，該公司第二季全球淨銷售額成長至 1.17 億美元，美國淨銷售額成長 23% 至 7,800 萬美元。正如預期的那樣，在新適應症上市的早期階段，絕大多數銷售額來自晚期皮膚鱗狀細胞癌，儘管面臨新的同類競爭，Libtayo 仍然是排名第一的全身性治療藥物。

Our launches in both advanced non-small cell lung cancer and basal cell carcinoma, or BCC, are progressing to plan. In BCC, Libtayo brand awareness is high among treating oncologists. We are encouraged by meaningful patient starts in the second quarter as Libtayo becomes a standard of care.

我們在晚期非小細胞肺癌和基底細胞癌（BCC）領域的產品上市均按計畫進行。在 BCC，Libtayo 品牌在治療腫瘤的醫生中知名度很高。在第二季度，隨著 Libtayo 成為標準療法，我們欣喜地看到患者數量顯著增加。

We're also making considerable progress in lung cancer where efforts are focused on establishing Libtayo in our monotherapy indication and will be important foundation for our potential future chemotherapy combination launch, which will be based on the data announced today. Our expanded field force is now fully deployed and securing early successes with treating physicians.

我們在肺癌領域也取得了相當大的進展，目前正致力於將 Libtayo 確立為單藥治療適應症，這將為我們未來可能推出的化療聯合療法奠定重要基礎，而這一基礎將基於今天公佈的數據。我們擴大的現場服務團隊現已全面部署，並已在治療醫生中取得了初步成功。

We're raising brand awareness, progressing formulary positioning and payer coverage. Lung cancer thought leaders recognized Libtayo's clinical differentiation, highlighting the rapid response rates and efficacy in patients with clinically stable brain metastases or high PD-L1 expression. In this highly competitive market, we remain focused on differentiating Libtayo and increasing physician experience. Today's exciting chemotherapy combination news has the potential to dramatically expand the patient opportunity for Libtayo in non-small cell lung cancer.

我們正在提高品牌知名度，推進藥品目錄定位和支付方覆蓋範圍。肺癌領域的思想領袖們認可了利妥昔單抗的臨床差異化作用，強調了其在臨床穩定的腦轉移或PD-L1高表達患者中的快速反應率和療效。在這個競爭激烈的市場中，我們將繼續專注於讓 Libtayo 脫穎而出，並提升醫生的使用體驗。今天令人振奮的化療合併用藥消息有望大幅擴大利妥昔單抗在非小細胞肺癌治療中的適用患者群體。

Turning now to Evkeeza, which was launched earlier this year in ultra-rare homozygous familial hypercholesterolemia. Key thought leaders recognized the benefits of Evkeeza, which delivers on efficacy, safety and tolerability in a market where many patients have struggled to stay on therapy in the face of life-threatening LDL cholesterol levels. We're encouraged by early initiations across switch and new-to-category patients and can see a future where Evkeeza becomes the standard of care.

現在讓我們來看看 Evkeeza，它在今年早些時候推出，用於治療極其罕見的純合子家族性高膽固醇血症。關鍵思想領袖們認識到 Evkeeza 的優勢，它具有療效、安全性和耐受性，而許多患者在面對危及生命的 LDL 膽固醇水平時難以堅持治療。我們對轉換治療和新用藥患者的早期啟動感到鼓舞，並看到了 Evkeeza 成為標準治療的未來。

Moving to Dupixent. Global net sales in the second quarter were $1.5 billion, growing 59% compared to the prior year. In the U.S., net sales grew 49% to $1.15 billion driven by broad-based growth across all approved indications. New patient starts are steadily growing and are above pre-COVID levels.

遷移至Dupixent。第二季全球淨銷售額為 15 億美元，比上年同期成長 59%。在美國，淨銷售額成長 49% 至 11.5 億美元，這得益於所有核准適應症的全面成長。新患者數量穩定成長，並已超過新冠疫情前的水準。

In atopic dermatitis, prescribing trends are strong across a spectrum of moderate-to-severe disease, including adolescent and pediatric patients. There is significant and sustained growth opportunity for Dupixent in a market where it is the #1 dermatologist prescribed biologic. This is based on its well-established efficacy and safety profile, broad label for patients as young as 6 years old and unmatched real-world physician and patient experience. In addition, as George outlined, we see an exciting future opportunities in dermatology, starting with CSU.

在異位性皮膚炎中，從中度到重度疾病，包括青少年和兒童患者，處方趨勢都很強勁。Dupixent 在市場上有巨大的持續成長機會，它是皮膚科醫生處方量排名第一的生物製劑。這是基於其已確立的療效和安全性，適用於 6 歲及以上患者的廣泛適應症，以及無與倫比的真實世界中醫生和患者的經驗。此外，正如喬治所概述的那樣，我們看到了皮膚病學領域令人興奮的未來機遇，而科羅拉多州立大學正是這一機會的起點。

Dupixent is the leading biologic in respiratory disease poised to capture meaningful growth now and in the future. Our asthma results outpaced recent competitive biologic launches. Launch preparations are underway in the pediatric asthma setting with the first regulatory approval expected in the U.S. this October.

Dupixent是呼吸系統疾病領域領先的生物製劑，預計在現在和未來將顯著成長。我們的氣喘治療效果超過了近期上市的其他生物製劑。目前，該藥物已在兒科氣喘領域展開上市準備工作，預計今年 10 月在美國獲得首個監管部門的批准。

In nasal polyps, there's high demand among ENTs and allergists with patients initiated regardless of prior surgery.

對於鼻息肉，耳鼻喉科醫生和過敏科醫生的需求量很大，患者無論之前是否接受過手術，都會開始接受治療。

In summary, we delivered strong performance across our brands with current and potential future launches on track to deliver sustained growth.

總而言之，我們旗下所有品牌均取得了強勁的業績，目前和未來可能推出的產品均按計劃進行，預計將持續成長。

Now I'll turn the call over to Bob.

現在我把電話交給鮑伯。

Thanks, Marion, and good morning and afternoon to everyone listening to the call. My comments today on Regeneron's financial results and outlook will be on a non-GAAP basis where applicable.

謝謝瑪麗昂，也祝所有收聽電話會議的朋友們早安/下午好。我今天對 Regeneron 的財務表現和展望的評論，在適用情況下將以非公認會計準則 (non-GAAP) 為基礎。

In the second quarter, our core business continued to deliver impressive year-over-year growth bolstered by strong execution across the company to deliver the full 1.25 million dose contract to the U.S. government for REGEN-COV.

第二季度，在公司各部門的強力執行下，我們的核心業務繼續實現了令人矚目的同比增長，成功向美國政府交付了 REGEN-COV 疫苗的全部 125 萬劑合約。

For the second quarter, total revenues grew 163% year-over-year to $5.1 billion. Excluding revenues related to the COVID-19 antibody cocktail, total revenue grew 22% versus the prior year. Total diluted net income per share grew 260% year-over-year to $25.80 on net income of $2.9 billion.

第二季總營收年增 163%，達到 51 億美元。剔除與 COVID-19 抗體雞尾酒療法相關的收入，總收入比前一年增長 22%。每股攤薄淨收益年增 260%，達到 25.80 美元，淨收益為 29 億美元。

In the second quarter, we recognized $2.6 billion of U.S. REGEN-COV sales, representing the vast majority of revenue related to the delivery of 1.25 million doses to the U.S. government. Due to revenue recognition rules, a residual $34 million of net product sales for doses delivered under this contract will be recorded in the third quarter. Given the delivery of these doses to the U.S. government and current utilization rates, we anticipate the current U.S. government's supply will be exhausted by the end of the year. We do not expect to record substantial additional sales this year in the U.S. unless the number of cases and related utilization continue to increase exponentially.

第二季度，我們確認了 26 億美元的美國 REGEN-COV 銷售額，其中絕大部分收入來自向美國政府交付的 125 萬劑疫苗。由於收入確認規則，根據該合約交付的劑量，剩餘的 3,400 萬美元淨產品銷售額將在第三季確認。鑑於這些疫苗已交付給美國政府，且目前的使用率來看，我們預計美國政府目前的疫苗供應將在年底前耗盡。除非病例數和相關使用量持續呈指數級增長，否則我們預計今年在美國不會錄得實質的額外銷售額。

I will now move to collaboration revenues, which were $955 million in the second quarter of 2021 as compared to $513 million second quarter of 2020.

接下來我將介紹合作收入，2021 年第二季為 9.55 億美元，而 2020 年第二季為 5.13 億美元。

Let me begin with the Roche collaboration. Ex U.S. sales of the COVID antibody cocktail known as Ronapreve outside of the U.S. were $470 million as reported to us by Roche. We recorded $168 million in Roche collaboration revenue for our share of profits from Roche's sale of Ronapreve, which is now available or approved in more than 20 countries. With new COVID cases on the rise globally, we expect the Ronapreve will continue to be a meaningful revenue contributor in 2021.

讓我先從與羅氏的合作說起。根據羅氏公司向我們報告，在美國以外地區，名為 Ronapreve 的 COVID 抗體雞尾酒療法的銷售額為 4.7 億美元。我們從羅氏公司銷售的 Ronapreve 產品中獲得 1.68 億美元的羅氏合作收入，該產品目前已在 20 多個國家上市或獲得批准。隨著全球新冠肺炎病例的增加，我們預計 Ronapreve 將在 2021 年繼續成為重要的收入貢獻者。

With regard to our Bayer collaboration, ex U.S. EYLEA net product sales, reported to us by Bayer, were $904 million for the second quarter of 2021, representing growth of 41% on a reported basis and 31% on a constant currency basis as a result of broad market recovery and a favorable comparison versus the prior year.

關於我們與拜耳的合作，拜耳向我們報告稱，2021 年第二季度美國以外的 EYLEA 淨產品銷售額為 9.04 億美元，按報告基準計算增長 41%，按固定匯率計算增長 31%，這得益於市場的全面復甦以及與上年同期相比的有利基數。

Total Bayer collaboration revenue was $349 million, of which we recorded $335 million for our share of net profits from EYLEA sales outside the U.S.

拜耳合作總收入為 3.49 億美元，其中我們從安永在美國以外的銷售中獲得的淨利潤份額為 3.35 億美元。

Finally, total Sanofi collaboration revenue was $438 million in the second quarter of 2021. Our share of the profits from the commercialization of Dupixent and Kevzara was $328 million, which nearly doubled when compared to profits of $172 million in the prior year.

最後，賽諾菲在 2021 年第二季的總合作收入為 4.38 億美元。我們從 Dupixent 和 Kevzara 的商業化中獲得的利潤份額為 3.28 億美元，與前一年的 1.72 億美元利潤相比，幾乎翻了一番。

Other revenue was $46 million in the second quarter compared to $212 million in the prior year. The decrease is primarily related to nonrecurring reimbursements from BARDA in 2020 for development of COVID-19 and Ebola treatments. We continue to expect 2021 other revenue to be less than half of what was recorded in 2020 on a full year basis.

第二季其他營收為 4,600 萬美元，而去年同期為 2.12 億美元。下降的主要原因是 2020 年 BARDA 為 COVID-19 和伊波拉治療藥物的研發提供的非經常性報銷款項減少。我們仍然預計 2021 年其他收入將不到 2020 年全年收入的一半。

Moving on to our operating expenses. R&D increased 11% year-over-year to $643 million, primarily due to continued clinical development costs for our REGEN-COV antibody cocktail and higher headcount to support our expanding pipeline.

接下來是我們的營運費用。研發投入年增 11% 至 6.43 億美元，主要原因是 REGEN-COV 抗體雞尾酒療法的持續臨床開發成本以及為支持不斷擴大的產品線而增加的人員配置。

Next, SG&A expense increased 21% year-over-year to $365 million due to costs related to COVID-19 related activities, launch investments for Libtayo, growth initiatives for EYLEA and higher headcount.

其次，由於與 COVID-19 相關活動的成本、Libtayo 的啟動投資、EYLEA 的成長計畫以及員工人數增加，銷售、一般及行政費用年增 21% 至 3.65 億美元。

Cost of goods sold increased versus the prior year from $93 million to $514 million primarily due to REGEN-COV manufacturing costs.

銷售成本較上年同期從 9,300 萬美元增至 5.14 億美元，主要原因是 REGEN-COV 的生產成本增加。

Finally, the effective tax rate was 17% in the second quarter of 2021, reflecting the impact of REGEN-COV sales, which were taxed at the U.S. statutory rate.

最後，2021 年第二季的實際稅率為 17%，反映了 REGEN-COV 銷售的影響，這些銷售按美國法定稅率徵稅。

Shifting to cash flow and the balance sheet. In the second quarter of 2021, Regeneron generated $478 million in free cash flow and ended the quarter with cash and marketable securities less debt of $5.1 billion. We received the full $2.625 billion of cash associated with completion of our second REGEN-COV contract with the U.S. government in July. As the business continues its strong performance, we are reiterating our capital allocation priorities of investing in internal R&D, funding strategic external R&D partnerships and returning cash to shareholders.

轉而關注現金流和資產負債表。2021 年第二季度，Regeneron 產生了 4.78 億美元的自由現金流，季度末現金及有價證券減去債務後為 51 億美元。7 月份，我們收到了與美國政府完成第二份 REGEN-COV 合約相關的全部 26.25 億美元現金。隨著公司業務持續強勁成長，我們重申了我們的資本配置優先事項，即投資內部研發、資助策略性外部研發合作以及向股東返還現金。

Accordingly, in July, we announced the new $1.8 billion expansion of our Tarrytown facilities primarily directed toward additional internal R&D operations and capabilities. We also continue to advance our next-generation technology partnerships with companies like Intellia and Alnylam, which are beginning to bear fruit as targets get selected and programs move forward into development.

因此，我們在 7 月宣布了對 Tarrytown 工廠進行 18 億美元的新擴建計劃，主要目標是增加內部研發運作和能力。我們也繼續推進與 Intellia 和 Alnylam 等公司的下一代技術合作，隨著目標的選定和專案的推進，這些合作開始取得成果。

Finally, in the second quarter, we repurchased $289 million of our shares, and we remain opportunistic buyers in the market.

最後，在第二季度，我們回購了價值 2.89 億美元的股票，我們仍然是市場上的機會主義買家。

To conclude, I'd like to provide select updates to our 2021 guidance. A complete summary of our latest full year guidance is available in our press release published earlier this morning. We are updating our full year 2021 guidance for SG&A to be in the range of $1.54 billion to $1.62 billion. The change is related to increased efforts in the second half for REGEN-COV.

最後，我想對我們 2021 年的指導方針做一些更新。我們最新的全年業績預期完整摘要已在今天早上早些時候發布的新聞稿中公佈。我們將 2021 年全年銷售、一般及行政費用預期更新為 15.4 億美元至 16.2 億美元。這項變更與下半年 REGEN-COV 計畫的加大投入有關。

We are also revising our full year 2021 guidance for R&D to be in the range of $2.65 billion to $2.75 billion. The change is driven by lower-than-expected spend on REGEN-COV.

我們同時將 2021 年全年研發投入預期調整為 26.5 億至 27.5 億美元。這一變化是由於 REGEN-COV 的支出低於預期所致。

Finally, we now expect our full year 2021 non-GAAP effective tax rate guidance to be in the range of 14% to 16% driven by higher sales of REGEN-COV, which, as I said, are taxed at the U.S. statutory rate.

最後，我們現在預計 2021 年全年非 GAAP 有效稅率指引值將在 14% 至 16% 之間，這主要得益於 REGEN-COV 銷售額的成長，正如我所說，REGEN-COV 是按美國法定稅率徵稅的。

In conclusion, Regeneron performed exceptionally well in the second quarter with the core business continuing on a strong growth trajectory as we invest in our diverse and differentiated pipeline for long-term sustainable growth.

總而言之，Regeneron在第二季度表現出色，核心業務繼續保持強勁的成長勢頭，我們正投資於多元化和差異化的產品線，以實現長期可持續成長。

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

那麼，我想把電話轉回給賈斯汀。

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

謝謝你，鮑伯。塔米婭，我們的演講稿到此結束。現在我們開始問答環節。（操作說明）

Please go ahead, Tamia.

請繼續，塔米亞。

(Operator Instructions) Your first question comes from the line of Chris Raymond with Piper Sandler.

（操作說明）你的第一個問題來自克里斯·雷蒙德和派珀·桑德勒的系列。

Just on the EMPOWER study, guys, we're getting a few questions the comp to Keytruda. I know it's hard to compare across trials, but it's a little bit tricky because EMPOWER had both squamous and non-squamous. But your 22-month median OS is right on top of the non-squamous experience for Keytruda, and I'm sure you're going to want to save a lot of detail for the full presentation, but can you maybe give us a sense of the balance here between squamous and non-squamous patients?

各位，關於 EMPOWER 研究，我們收到了一些關於 Keytruda 的比較問題。我知道很難在不同試驗之間進行比較，但這有點棘手，因為 EMPOWER 試驗既包括鱗狀細胞癌也包括非鱗狀細胞癌。但您的 22 個月中位總生存期與 Keytruda 治療非鱗狀細胞癌的經驗相當，我相信您會想在正式演講中保留很多細節，但您能否讓我們了解一下鱗狀細胞癌患者和非鱗狀細胞癌患者的療效平衡情況？

As you said, I mean, we're going to provide the details in future publication and/or conferences. I think it's important to note, as you said, it's very difficult to compare cross studies done years apart and especially when we allowed classes of patients that were not previously allowed in other studies and so forth.

正如您所說，我們將在未來的出版物和/或會議上提供詳細資訊。我認為需要指出的是，正如你所說，比較相隔數年進行的交叉研究非常困難，尤其是當我們允許納入以前其他研究不允許納入的患者類別時等等。

As you pointed out, the median survival numbers are right on top of each other. But as you also point out, we had 2 different subtypes in this study. I can comment in our preliminary analyses, and these remain to be fully validated and so forth. In one of the subtypes, our hazard ratio was better than what was observed with the Keytruda study and the other one, it was worse. It's important to point out that these things bounce around in these cross-study comparisons. As you know, in other settings, if try to do cross country -- cross-study comparisons, for example, when you compare our monotherapy results in the greater than 50% PDL population, it looks like our numbers are substantially better in the skin and particularly with the CSCC comparisons they're better. So these things bounce around. It's always hard to do these things.

正如你所指出的，中位數存活率數字非常接近。但正如您所指出的，本研究中我們有兩種不同的亞型。我可以對我們的初步分析發表意見，但這些分析仍需進一步驗證等等。其中一種亞型的風險比Keytruda研究觀察到的結果好，而另一種亞型的風險比則更差。需要指出的是，這些因素在這些跨研究比較中會發生變化。如您所知，在其他情況下，如果嘗試進行跨國——跨研究比較，例如，當您比較我們在 PDL 患者中超過 50% 的單藥治療結果時，我們的數據在皮膚方面明顯更好，尤其是在 CSCC 比較中，我們的數據更好。所以這些東西到處亂竄。做這些事總是很困難的。

But I think the important thing to point out is that in this field in lung cancer, very few have hit in both monotherapy greater than 50% and in chemo combination all comers. I remind you that Opdivo gained than most of the PD-L1s did. So right now, there is only 2 PD-1 antibodies that standalone, having demonstrated overall survival benefit, both in the monotherapy setting as well as now in the chemo combination setting. I think this really well positions Libtayo and across all the studies, I think it's -- the definitive conclusion is that it's a very active molecule that looks at least as active as any other agents out there.

但我認為需要指出的是，在肺癌領域，很少有藥物能在單藥治療有效率超過 50% 和化療聯合治療有效率方面都達到全勝。我提醒你，Opdivo 的收益比大多數 PD-L1 晶片都要高。所以目前只有 2 種 PD-1 抗體可以單獨使用，並且已經證明可以提高總生存期，無論是在單藥治療中還是在現在的化療聯合治療中。我認為這使得 Libtayo 的市場地位非常穩固，而且綜合所有研究來看，最終的結論是，它是一種非常活躍的分子，其活性至少與其他任何藥物一樣強。

Your next question comes from the line of Cory Kasimov with JPMorgan.

你的下一個問題來自摩根大通的科里·卡西莫夫。

This is Gavin on for Cory. Just a follow-up on the last question. In terms of longer-term outlook for Libtayo in lung specifically, you talked about the IO/IO combo as kind of the differentiating strategy. I'm just wondering if you're maintaining that position? Or with the results in hand today, that view has changed?

這裡是加文替科里報道。再補充一下上一個問題。就 Libtayo 在肺部的長期前景而言，您曾談到 IO/IO 組合是一種差異化策略。我只是想知道你是否仍然堅持這個立場？或者，根據今天的結果，你的看法已經改變了？

Yes. Well, we think that certainly we should be competitive right now. The opportunity for this class, which is obviously dominated by Keytruda right now because up until now it was the only agent that had this strong data across the spectrum of monotherapy and chemo combination. We think that now we can be legitimate competitors here in the lung cancer space.

是的。我們認為，我們現在絕對應該具備競爭力。目前，Keytruda 顯然主導了這一類藥物的市場，因為到目前為止，它是唯一一種在單藥治療和化療聯合治療方面都擁有如此強大數據的藥物。我們認為，現在我們可以成為肺癌領域名副其實的競爭者。

We see our combination opportunities as future growth in differentiator opportunities. But in the short term, we expect to be a viable competitor now with these data. And in the future, we hope to use the combinations to take the standard of care and elevate results to another level.

我們認為合併帶來的機會是未來差異化成長的機會。但就短期而言，憑藉這些數據，我們預期現在將成為有競爭力的競爭對手。未來，我們希望利用這些組合療法，將護理標準提升到一個新的水平，並將治療效果提高到一個新的水平。

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

你的下一個問題來自 Ronny Gal 與 Bernstein 的對話。

Question on the [immunco]. Can you talk a little bit about the path to establish that antibody cocktail as a treatment for patients who are immunocompromised before treatment -- before cancer treatment and so forth? You need to have full authorization to begin to pursue this. But if we think about the product longer term beyond the current wave of the epidemic, what steps are you making towards establishing it as a long-term part of the treatment paradigm in various diseases?

關於[immunco]的問題。您能否談談如何將這種抗體雞尾酒療法確立為免疫功能低下患者在接受治療前（例如癌症治療前）的治療方法？您需要獲得完全授權才能開始推進此事。但如果我們從更長遠的角度來看待該產品，超越當前的疫情浪潮，您正在採取哪些措施，使其成為各種疾病治療模式的長期組成部分？

Yes. As you said, we think that the immunocompromised population which, as I'm sure you all know, represents 3% to 4% of the U.S. population, that several million individuals, a variety of studies are showing that somewhere around 50% or more of these individuals do not respond after 2 or even after 3 attempts with the vaccine. And so these people are left without their own antibodies to protect them.

是的。正如您所說，我們認為免疫功能低下的人群（我相信大家都知道，這部分人群占美國人口的 3% 到 4%），也就是數百萬人，各種研究表明，其中大約 50% 或更多的人在接種疫苗 2 次甚至 3 次後都沒有產生反應。因此，這些人體內缺乏抗體來保護自己。

So it's a huge unmet need setting where these individuals will not be protected. And as we're all seeing that it's very unlikely that we will be eliminating spread of infections through breakthrough infections, whether it was symptomatic or otherwise throughout the population and for these individuals to be able to live normal lives, they're going to need protection.

因此，這是一個巨大的未滿足需求領域，這些人將無法受到保護。我們都看到，透過突破性感染來消除傳染病的傳播（無論是否有症狀）的可能性非常小，為了讓這些人能夠過正常的生活，他們需要保護。

And we believe that the most powerful protection is essentially providing them with these surrogate antibodies that our antibody cocktail provides. We already have very strong data, we believe, to support the notion that this agent can be used in chronic prevention settings, and we do intend to continue to explore future study opportunities where we can further enhance on the already existing data that shows that after the first week or so, we seem to obtain somewhere upwards of 90% protection against infection in individuals who do not have their own antibodies and are being exposed to the SARS-CoV-2 virus. I think that is very strong data that bodes very well that this is in -- potential to be a very important treatment, particularly for these immunocompromised individuals who do not have antibodies of their own.

我們相信，最有效的保護措施本質上是為他們提供我們的抗體混合物所提供的這些替代抗體。我們相信，我們已經有非常強有力的數據來支持這種藥物可用於慢性預防的觀點，並且我們打算繼續探索未來的研究機會，以便進一步加強現有數據，這些數據表明，在大約一周後，對於沒有自身抗體並暴露於 SARS-CoV-2 病毒的個體，我們似乎可以獲得高達 90% 的感染保護率。我認為這是非常強大的數據，預示著這種療法很有可能成為一種非常重要的治療方法，特別是對於那些自身沒有抗體的免疫功能低下的人來說。

Yes. Let me just add that what's implicit and what George said is we're working with the agency to try and convince them that our data is strong. And -- the agency, obviously, has a lot on its plate, and it's trying, I think, to sort through whether or not these individuals should try a third dose or not of a vaccine. That has to get sorted out, I think. And the FDA has our data. And as George said, we're looking at ways to enhance our data, but we already believe that in a pre-exposure prophylaxis mode we have strong data, but it's not been authorized yet by the agency and it's under review.

是的。我還要補充一點，喬治所說的意思是，我們正在與該機構合作，試圖說服他們我們的數據是可靠的。而且——顯然，該機構有很多事情要處理，我認為，它正在努力弄清楚這些人是否應該嘗試接種第三劑疫苗。我認為這個問題必須解決。FDA已經掌握了我們的數據。正如喬治所說，我們正在尋找方法來增強我們的數據，但我們已經相信，在暴露前預防模式下，我們有強有力的數據，但尚未獲得該機構的授權，目前仍在審查中。

So am I to understand you're seeking a label for chronic treatment of immunocompromised population and that you think you have the data at hand to obtain such a label?

所以，我的理解是，您正在尋求一種用於治療免疫功能低下人群慢性疾病的藥物標籤，並且您認為您手頭上已有數據可以獲得這樣的標籤？

So just to be clear, the current authorization allows chronic treatment but allows chronic treatment for people, for example, who are immunocompromised, but are in a institutional setting, working or living in a congregate setting where they're exposed to infected individuals, we would like to expand that to pre-exposure prophylaxis for the community-acquired infections. That is where immunocompromised people might be able to go out in the community and have some protection.

為了明確起見，目前的授權允許對慢性病患者進行治療，例如免疫功能低下的人，但他們身處機構環境，在集體環境中工作或生活，會接觸到感染者。我們希望將授權範圍擴大到社區獲得性感染的暴露前預防。這正是免疫功能低下的人可以外出到社區並獲得一定保護的地方。

So we do have chronic dosing for the immunocompromised in our current authorization, but that's restricted to this post exposure or ongoing exposure in the known infected people setting, and we're trying to expand that to protect these people in the community setting. It's -- we think the data are strong. But obviously, there's a lot going on and a lot of considerations, as I mentioned before, that need to get sorted out.

因此，我們目前的授權中確實包含了針對免疫功能低下者的慢性給藥方案，但這僅限於已知感染者在暴露後或持續暴露的情況下，我們正在努力擴大其適用範圍，以保護社區環境中的這些人。我們認為數據很有說服力。但很顯然，正如我之前提到的，有很多事情需要處理，也有很多需要考慮的事情。

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

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

So many questions. Perhaps one for Marion on EYLEA, a really strong result. And by the way, congratulations on the spectacular quarter. On EYLEA, tremendous return to growth. Marion, could you talk about whether there was any catch-up in the second quarter? Or is this a sustainable revenue run rate going forward? Because it's clearly significantly above where we were expecting. And then perhaps you could just give us a little bit more color on the proportion of AMD and DME.

好多問題。或許瑪莉安在 EYLEA 的表現非常出色。順便祝賀你們取得如此輝煌的季度業績。EYLEA實現了巨大的成長復甦。瑪莉昂，你能談談第二節比賽中球隊是否有追趕的跡象嗎？或者說，這樣的營收成長率能否持續下去？因為它明顯遠遠超出我們的預期。然後，您或許可以再詳細解釋 AMD 和 DME 的比例。

Sure. And thank you, Geoff. Yes, delighted to comment. We did have a very strong quarter. And certainly, our EYLEA performance was driven by return of market growth and our own share gains versus competition in capturing that market growth. In the quarter, we did see a return of patient flow to offices consistent with the pre-pandemic period. And there also is the consideration of some patients who may have delayed treatment coming back in. So it's a combination of factors but certainly a very strong performance for EYLEA.

當然。謝謝你，傑夫。是的，我很樂意發表評論。我們本季業績非常出色。當然，安永的業績成長得益於市場成長的恢復以及我們在搶佔市場成長份額方面相對於競爭對手的進步。本季度，我們確實看到診所的患者流量恢復到了疫情前的水平。此外，也要考慮到一些可能因治療延誤而重新入院的患者。所以這是多種因素共同作用的結果，但對安怡來說，這無疑是一項非常強烈的業績。

As well, to your question related to future growth by indication, we do continue to see diabetic eye disease as the indications that have the highest growth trajectory. So that's balancing out our wet AMD business, which is still the majority of roughly 50%, 52%, 55% of overall use of EYLEA.

另外，關於您提出的有關未來適應症成長的問題，我們仍然認為糖尿病眼疾是成長軌跡最高的適應症。這樣就平衡了我們的濕式 AMD 業務，該業務仍佔 EYLEA 整體使用量的約 50%、52%、55%。

Your next question comes 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。

Great. Maybe a question for Marion and Bob relating to REGEN-COV2. Are you -- in order to get the next U.S. government order, do you -- are you waiting for approval? Or are they just waiting to exhaust their current supply and then reorder?

偉大的。或許可以問 Marion 和 Bob 一個關於 REGEN-COV2 的問題。為了獲得下一份美國政府訂單，您是否正在等待批准？或者他們只是在等待用完現有庫存後再重新訂購？

Maybe I'll take that question. The contract we have has been fulfilled. And so the government is going to need to decide whether or not they want to have another contract or they want us to switch over to a commercial model, which could occur before or after a regular approval as it did with Remdesivir.

或許我會回答這個問題。我們簽訂的合約已經履行完畢。因此，政府需要決定是想再簽一份合同，還是想讓我們轉而採用商業模式，這可能在獲得常規批准之前或之後發生，就像瑞德西韋的情況一樣。

I think a lot of that is going to depend upon the government's assessment of what they think is the most efficient way to get people to use that product. There's been a tremendous acceleration in use. Our penetration in terms of addressing what we would say, estimated eligible patients has gone up dramatically to somewhere in the low single digits to almost 25% to 30% more recently in terms of eligible patients getting monoclonals.

我認為這很大程度上取決於政府如何評估讓人們使用該產品的最有效方法。使用量出現了巨大的成長。就我們所說的符合條件的患者而言，我們的滲透率已經大幅上升，從個位數增加到最近接近 25% 至 30%（以接受單株抗體治療的符合條件的患者為準）。

If that trend continues along with the trend of unfortunately, more cases, obviously, we're going to have to go with the direction that the government wants, another contract or a commericial switchover. Capacity, of course, is always an issue, but we think we're sort of well positioned to continue to supply similar amounts that we've been able to supply and we'll have to look at -- and these demands continued pretty rapidly. And of course, we do have our partner, Roche, who's got capacity that we can perhaps turn to. So a lot of moving parts, Yaron. And the most important of which is what is the shape of the current surge in the pandemic.

如果這種趨勢繼續下去，而且不幸的是，病例還在增加，顯然，我們將不得不按照政府的意願行事，要么簽訂另一份合同，要么進行商業轉換。當然，產能始終是一個問題，但我們認為我們有能力繼續供應與以往類似的數量，而且我們將不得不考慮——這些需求持續快速增長。當然，我們還有合作夥伴羅氏，他們擁有我們可以藉助的產能。所以牽涉的環節很多，亞倫。其中最重要的是，當前疫情激增的形態如何。

Your next question comes from the line of Terence Flynn with Goldman Sachs.

你的下一個問題來自特倫斯·弗林在高盛集團的經歷。

Congrats on the Dupixent CSU data. I was just wondering if there's incremental SG&A that's going to be required to launch this indication or if you'd be able to leverage your existing commercial footprint? And then the corollary is just how to think about the continued ramp on profitability of the JV here into 2022? Are there any other significant investments that we need to consider in our models?

恭喜你獲得Dupixent CSU數據。我只是想知道，推出這項適應症是否需要增加銷售、管理及行政費用，或者您能夠利用現有的商業佈局？那麼，由此引申的問題是，如何看待合資企業在 2022 年持續提高獲利能力的問題呢？我們的模型中是否還需要考慮其他重大投資？

So Terence, I'll start from the commercial perspective. So yes, we're really excited about adding potentially another indication for Dupixent. CSU is a large opportunity. They're about 300,000 potential patients with disease adults and very limited treatment options for them today.

那麼，特倫斯，我將從商業角度開始談起。是的，我們非常高興Dupixent可能又將迎來一個新的適應症。科羅拉多州立大學是一個巨大的機會。目前約有 30 萬名成年患者可能患有此病，但可供選擇的治療方案非常有限。

We will be able to always look at the impact of our educational abilities and promotion by indication. But to your very clear point, we do have a leveraging opportunity here because we're already calling on the audiences that would be required to effectively promote CSU. It's premature for us to say absolutely what sort of additional effort we might need. But certainly, we will be able to leverage our current footprint in all areas.

我們將能夠始終透過指標來審視我們的教育能力和晉升所帶來的影響。但正如您所指出的，我們確實有一個可以利用的機會，因為我們已經在向有效推廣 CSU 所需的受眾群體發出呼籲。現在就斷言我們可能需要付出哪些額外的努力還為時過早。但可以肯定的是，我們將能夠利用我們在各個領域的現有優勢。

Yes. And Terence, I'll just kind of punctuate what Marion said on that. Clearly, and you can see it in the MD&A that we disclosed, and you can do the calcs, right, our margins are getting better with this. I mean this is something that we talked about.

是的。特倫斯，我只想補充一下瑪莉安剛才說的話。很明顯，正如我們在管理層討論與分析中所揭露的那樣，你也可以自己計算一下，我們的利潤率因此得到了改善。我的意思是，這是我們討論過的事情。

Certainly, we've had a lot of ex U.S. launches, a lot of prelaunch expenses related to that, which kind of held that back a little bit. I think you're now seeing certainly year-over-year, you're starting to see the fruits of the labor. And the leverage that we've been talking about for a while, again, kudos to Sanofi, another strong ex U.S. quarter by them as we continue to see the indications really starting to kick in ex U.S.

當然，我們有很多在美國以外地區推出的產品，也因此產生了許多上市前的費用，這在某種程度上阻礙了產品的發展。我認為你現在肯定已經看到，與往年相比，你開始看到努力的成果了。我們一直在談論的槓桿作用，再次讚揚賽諾菲，他們在美國以外的另一個季度表現強勁，我們繼續看到美國以外的跡象開始真正發揮作用。

Your next question comes from the line of Kennen MacKay with RBC Capital Markets.

你的下一個問題來自加拿大皇家銀行資本市場的 Kennen MacKay。

Huge congratulations on the quarter, really across the board commercially and clinically with a couple of surprises this season. Maybe a question on EYLEA. There was commentary from another call earlier this Q2 earnings season that included conversation around somewhat aggressive development plans of an EYLEA biosimilar. Just wondering sort of beyond the 2023 composition of matter patent, if you could talk to which intellectual property you have the most confidence in, in keeping this franchise going, especially as it relates to the U.S.? Congrats again.

恭喜你們本季的全面成功，無論是商業上或臨床上，都表現出色，本季還有一些令人驚訝的成果。或許可以問一個關於愛立信的問題。在第二季財報季早些時候的另一次電話會議上，曾有人評論說，公司正在製定一項較為激進的安永生物類似藥開發計畫。我只是想問一下，除了2023年的物質組成專利之外，您能否談談您最有信心的哪項智慧財產權能夠維持這個品牌的延續，尤其是在美國方面？再次恭喜。

Right. It's a great question, but we're going to have to defer on that one because of ongoing patent issues and what have you. We really can't make a comment. Sorry.

正確的。這是一個很好的問題，但由於專利問題等原因，我們暫時無法回答這個問題。我們實在不便置評。對不起。

Your next question comes from the line of Carter Gould with Barclays.

你的下一個問題來自卡特·古爾德在巴克萊銀行的職位。

Obviously -- I want to kind of change gears a bit. Obviously, we've seen some pretty transformational events across how FDA is addressing Alzheimer's since your last quarterly call. You did announce a early-stage program in conjunction with Alnylam, but just wanted to see if -- you gauge your appetite to jump in sort of the antibody-directed amyloid beta lowering game. There's a few companies that innovate and iterate antibodies as well as Regeneron. And so as you think about your Alzheimer's effort going forward, if that was a point of focus and any broader color on that space would be helpful?

顯然——我想稍微換個話題。顯然，自從您上次季度電話會議以來，FDA 在應對阿茲海默症方面已經發生了一些相當大的變革性事件。您確實宣布了與 Alnylam 合作的早期項目，但只是想看看——您是否有興趣涉足抗體導向的降低澱粉樣蛋白β的領域。除了 Regeneron 之外，還有一些公司在抗體創新和迭代方面也做得非常出色。那麼，當您考慮未來如何應對阿茲海默症時，如果這是一個關注點，那麼關於這個領域的更廣泛資訊是否會有幫助？

Well, we should let the iterator and inventor answer that.

嗯，這個問題應該要讓迭代器和發明家來回答。

Sorry.

對不起。

I'm sorry, I was just saying we should let the iterator and inventor answer that. Go ahead, George.

抱歉，我只是說我們應該讓迭代器和發明者來回答這個問題。請繼續，喬治。

Okay. I was going to just -- sorry, I didn't hear you speaking here. Yes, we have a very robust effort in neurodegenerative diseases here at Regeneron. We are not overly excited about some of the antibody developments and necessarily getting into those type of approaches. But we have a lot of things that we're actually very excited about in the neurodegenerative disease space. We think novel ways of addressing targets as well as brand new targets that haven't been discovered elsewhere. We will be discussing these efforts going forward in more detail over the coming months and year.

好的。我本來想說——抱歉，我沒聽到你說話。是的，Regeneron 在神經退化性疾病領域投入了大量精力。我們對某些抗體研發進展並不十分興奮，也不一定要採用這類方法。但在神經退化性疾病領域，我們有很多事情讓我們感到非常興奮。我們思考解決現有目標的新方法，以及在其他地方尚未發現的全新目標。在接下來的幾個月和一年裡，我們將更詳細地討論這些工作。

Your next question comes from the line of Brian Skorney with Baird.

你的下一個問題來自 Brian Skorney 與 Baird 的對話。

Unfortunately, I kind of feel like this is going to be an evergreen question as we see SARS-CoV-2 to genetic shift. But it seems like just this week, there's been some emergence of data for the lambda strain showing potentially increased resistance of vaccination. Just wondering if you guys have any data yet on the antibody combo and how much activity might retain against the strain?

不幸的是，我覺得隨著 SARS-CoV-2 病毒的基因變異，這個問題將會一直存在。但似乎就在本週，出現了一些關於λ毒株的數據，顯示其對疫苗的抵抗力可能有所增強。想問你們有沒有關於抗體組合的數據，以及這個組合對株能保留多少活性？

Yes. I have to say that I'm not sure exactly what our results are and quantitatively. But so far, every variant and every strain that we've tested, we retained potency. And so far, there's hopefully no reason to think that's going to change because we prospectively took advantage of this cocktail approaches so that even if one antibody gets minimally affected the other one can take its place. So we expect to retain robust activity.

是的。我必須說，我不太確定我們的結果究竟是什麼，也不確定具體是哪些量化指標。但到目前為止，我們測試過的每一個變種和每一個菌株都保持了效力。到目前為止，希望沒有理由認為這種情況會改變，因為我們預先利用了這種混合療法，這樣即使一種抗體受到輕微影響，另一種抗體也可以取而代之。因此，我們預計市場活動將保持強勁勢頭。

That said, I think we've also announced that we have second-generation antibodies that are also entering in the clinic where we're going to continue to retain broad coverage. But I believe that as far as it's been tested with lambda, we retain potency there as well.

也就是說，我認為我們也已經宣布，我們擁有第二代抗體，這些抗體也正在進入臨床試驗階段，我們將繼續保持廣泛的覆蓋範圍。但我相信，就目前對λ噬菌體的檢驗結果來看，它同樣能保持效力。

Your next question comes 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 just wanted to ask on commercial Libtayo. Just wanted to see what sort of success or what metrics you can give us commercially with the initial first-line lung monotherapy rollout as well as the derm indication as well to see how that's going early in the launch?

我只是想問關於商業版Libtayo的問題。我只是想了解一下，在最初的一線肺部單藥療法推廣以及皮膚科適應症方面，您能提供哪些商業方面的成功指標或衡量標準，以了解該療法在上市初期進展如何？

Sure, Geoff. Happy to. So for Libtayo with our first lung indication in mono, as expected, that is the smaller indication. So we're really excited about the chemotherapy combination data that was shared today. And in fact, if I quantify it, that indication in terms of patient potential is about 4x the size of the mono indication. But what we're doing today in the market commercially is certainly foundational to Libtayo and our oncology portfolio more broadly. I'll comment, we are still the standard of care in cutaneous squamous cell carcinoma. That was a very effective launch. We now have a competitor in that indication, but we retain our leadership.

當然可以，傑夫。樂意之至。因此，對於 Libtayo 而言，其首個肺部適應症為單核細胞增多症，正如預期的那樣，這是較小的適應症。所以我們對今天公佈的化療合併用藥數據感到非常興奮。事實上，如果我量化一下，就患者潛力而言，該適應症的規模大約是單一適應症的 4 倍。但我們今天在市場上所做的商業活動，對於 Libtayo 以及我們更廣泛的腫瘤產品組合來說，無疑是基礎性的。我想說的是，我們在皮膚鱗狀細胞癌的治療方面仍然處於行業領先地位。這是一次非常成功的發表會。現在我們在這個領域有了競爭對手，但我們仍然保持領先地位。

The basal cell carcinoma launch is also going well. And certainly, the efficacy and tolerability, safety of Libtayo is paramount for those patients, and we offer an alternative where the specialists in that area do believe Libtayo as evolving to become the standard of care. It's early days in lung. I think our team is doing a really good job. And when we talk to the opinion leaders, they're most excited, as I mentioned, about our rapid action, our efficacy, even in those patients with stable brain metastases and with the high expression PD-L1 patients. So early days, we are right on track with where we expected to be, but there's a lot more potential and a lot more work to do.

基底細胞癌的上市進展也很順利。當然，Libtayo 的療效、耐受性和安全性對這些患者來說至關重要，我們提供了一種替代方案，該領域的專家也認為 Libtayo 正在發展成為標準療法。肺部疾病的研究還處於早期階段。我認為我們團隊做得非常出色。正如我之前提到的，當我們與意見領袖交談時，他們最興奮的是我們快速的行動和療效，即使是對那些腦轉移穩定的患者和 PD-L1 高表達的患者也是如此。雖然目前還處於早期階段，但我們正如預期發展，不過還有更大的潛力，還有很多工作要做。

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

你的下一個問題來自阿萊西亞·楊和坎托·菲茨杰拉德的血脈。

I just wanted to talk a little bit about how you guys see what the therapeutic goals are for -- in NASH for medicine since you're a leader in genetics and there's been a lot of ups and downs in NASH?

我只是想和你們談談你們如何看待 NASH 的治療目標——尤其是在醫學領域，因為你們是遺傳學領域的領導人物，而 NASH 的發展也經歷了很多起伏？

Well, I think there's a variety of goals, but our major question right now with our first program is we believe that we have a novel approach that addresses not the steatosis component but the inflammatory component, which is something that really is not being addressed by other approaches, other targets, other agents so that if we can actually stop or reverse the inflammatory response to the steatosis that will be an entirely different and also potentially complementary approach to what anything and anybody else is doing right now.

嗯，我認為目標有很多種，但我們目前第一個項目的主要問題是，我們相信我們有一種新穎的方法，它解決的不是脂肪變性本身，而是發炎成分，這是其他方法、其他目標、其他藥物真正沒有解決的問題。因此，如果我們能夠真正阻止或逆轉脂肪變性的發炎反應，那將是一種完全不同且可能與目前任何其他方法互補的方法。

I think the genetics very strongly point to that. That's what it actually shows that this genetic target affects and that's what the protective mutations are actually showing. So we're excited about looking at this opportunity, whether we can halt or even reverse inflammatory signals, inflammatory processes and thus, actual progression of the disease irregardless of steatosis.

我認為基因學證據非常有力地顯示了這一點。這實際上表明該基因靶點會影響這一點，而保護性突變實際上也表明了這一點。因此，我們對這個機會感到興奮，我們能否阻止甚至逆轉發炎訊號、發炎過程，從而阻止疾病的實際進展，而不管是否存在脂肪變性。

Your next question comes from the line of Mike King with H.C. Wainwright.

你的下一個問題來自 Mike King 和 H.C. Wainwright 的對話。

I'm not sure how long -- how quickly this question could be answered, but I'm just trying to get a better appreciation of what I would call the real-world use of REGEN-COV. Can you point to -- I think Len said something about 25% of patients, but I think that was eligible. I don't know if you have any market data from real-world use versus what's been shipped and paid for -- shipped to and paid for by the government? Can we understand how that rubber band flexes a little bit more?

我不確定這個問題需要多久才能得到解答，但我只是想更了解我所謂的 REGEN-COV 在現實世界中的應用。你能指出──我記得Len說過大約25%的患者，但我認為那隻是符合條件的。我不知道你們是否有來自實際使用情況的市場數據，與已發貨並已付款的產品（包括已發貨並由政府付款的產品）進行比較？我們能理解為什麼那根橡皮筋還能再彎曲一點嗎？

Sure. So look, what we look at are the shipments from our distributor to institutions, hospitals, med centers and clinics, emergency rooms, et cetera, et cetera. And we believe, based on some real-world data, that about 70% of the daily cases that occur are occurring in people who would be eligible for treatment, either because they're obese or they've got underlying conditions or they're elderly more -- we're seeing more younger and obese, frankly, than we -- than elderly that was seen earlier in the pandemic.

當然。所以你看，我們關注的是從我們的經銷商到機構、醫院、醫療中心和診所、急診室等等的貨物運輸情況。根據一些真實世界的數據，我們認為，每天發生的病例中約有 70% 發生在符合治療條件的人群中，要么是肥胖，要么是患有基礎疾病，要么是老年人——坦白說，我們看到的年輕人和肥胖者比疫情早期看到的老年人更多。

So if you take, for example, that maybe it was 100,000 new cases, maybe 70,000 of them would be eligible. So that gives you an idea. I was just looking, Mike, at this to see what our repeat orders were. And the vast, vast majority, I think it's around or above 90% of the institutions ordering have -- are repeat orders, meaning that they're not people just stocking the stuff to have it around. They're using it up. And that's what our field people seem to tell us. I don't know if Marion wants to maybe add anymore on that or not, but I hope that helps you.

例如，假設新增病例有 10 萬例，其中可能有 7 萬例符合資格。這樣你就能明白我的意思了。麥克，我只是在查看這個，看看我們的回頭客訂單情況。而且，我認為絕大多數（大約 90% 或以上）訂購的機構都是重複訂購，這意味著他們不是為了囤貨而囤貨。他們正在把它用完。而我們的第一線人員似乎也告訴我們是這樣的。我不知道瑪麗昂是否還想補充什麼，但我希望這對你有幫助。

That would be the characterization. I think the other thing that's important is, we are continuing to educate and to help with some of the bottlenecks that have been experienced early days. So we are seeing growing utilization. And certainly, as Len mentioned, the patient criteria who are eligible for treatment is broad, to Len's point, age-related obesity, hypertension, diabetes, respiratory immune issues. So there are a lot of patients who are very much in need of treatment, and we're doing everything we can to help them have availability of product.

這就是對人物的描述。我認為另一個重要的事是，我們將繼續進行教育，並幫助解決早期遇到的一些瓶頸問題。因此，我們看到利用率正在不斷提高。當然，正如 Len 所提到的，符合治療條件的患者標準很廣泛，正如 Len 所指出的，包括與年齡相關的肥胖、高血壓、糖尿病、呼吸系統免疫問題。因此，有許多患者非常需要治療，我們正在盡一切努力幫助他們獲得產品。

Yes. I'll just add a couple of thoughts or points to that is during the last sort of surge, as Len said, we were probably only reaching somewhere near 1% of the potentially eligible patients. We're now well into the double digits in terms of the percentage of the eligible patients that we're probably reaching. And we've had some feedback from some of these institutions where we distribute to where they're actually low on inventory, suggesting that they're not stocking it up.

是的。我只想補充幾點想法或觀點，正如 Len 所說，在上一次疫情高峰期間，我們可能只接觸到了大約 1% 的潛在合格患者。現在，我們接觸到的符合條件的患者比例已經達到兩位數以上了。我們從一些分銷機構那裡得到了一些回饋，這些機構的庫存實際上很低，這表明他們沒有儲備物資。

Yes. The other thing, just to add because we obviously are all over this and get the individual stories, but the one thing that is so consistent, when patients are doing poorly and then they're treated with REGEN-COV within a day, 2 days, they see a remarkable difference in the patient status that truly has been rewarding for those on the front line.

是的。還有一點需要補充，因為我們顯然都在關注此事，也了解了每個人的情況，但有一點非常一致：當患者病情惡化時，如果他們在一兩天內接受 REGEN-COV 治療，患者的病情就會發生顯著變化，這對於一線人員來說確實是一種莫大的安慰。

Our final question comes from the line of Yatin Suneja with Guggenheim Partners.

我們最後一個問題來自古根漢合夥公司的亞廷·蘇內賈。

Just a question on the Intellia collaboration. Can you just share your views on the gene editing space. Your vision or where do you see the new indication and obviously, the strategic goal of the broad collaboration that you have with Intellia?

關於與Intellia的合作，我有個問題。能否分享一下您對基因編輯領域的看法？您對新指標的願景，或者說您如何看待與 Intellia 的廣泛合作的策略目標？

Yes. Obviously, these first-in-human results are incredibly exciting, both in terms of the percent knockdown and also in terms of thus far in these early days, the observed safety. And as we said, we have 2 types of broad collaborative program areas with Intellia, both of which we think are greatly bolstered in terms of confidence based on these initial results. We have a series of programs which similarly involve systemic-based approaches to achieve gene knockdown.

是的。顯然，這些首次人體試驗結果令人無比興奮，無論是從擊倒率來看，還是從目前觀察到的早期安全性來看，都是如此。正如我們所說，我們與 Intellia 有 2 種廣泛的合作項目領域，我們認為，基於這些初步結果，這兩個領域的信心都得到了極大的增強。我們有一系列類似的方案，這些方案都涉及基於系統的方法來實現基因敲低。

So obviously, those are -- chances of success are greatly bolstered by what we've seen with these first-in-human results. But we also have, I think, just as if not even more exciting, a CRISPR-based gene insertion program that we're very excited about. And since it depends on essentially overlapping technologies, this program and its chance of success has greatly been increased based on the results we've seen to date.

顯然，這些首次人體試驗的結果大大提高了成功的機會。但我認為，我們還有一個基於 CRISPR 的基因插入計劃，這同樣令人興奮，甚至更加令人興奮，我們對此感到非常興奮。由於該計劃主要依賴重疊的技術，根據我們迄今為止所看到的結果，該計劃及其成功的機會大大增加。

So we think that with the fact that we have so many programs ongoing in our collaboration with Intellia, more than 20 programs under evaluation, and we have the ability to move forward quite a few of these, we're very excited that this could really change the practice of medicine and really bring CRISPR-based gene therapy to patients into the world. So nothing to be more exciting from the gene medicines point of view.

因此，我們認為，鑑於我們與 Intellia 合作開展瞭如此多的項目，其中有 20 多個項目正在評估中，而且我們有能力推進其中相當一部分項目，我們非常興奮，因為這真的可以改變醫學實踐，真正將基於 CRISPR 的基因療法帶給世界各地的患者。所以從基因藥物的角度來看，沒有什麼比這更令人興奮的了。

Thank you, everyone. Thanks for hanging in there a little longer today. Bob, Landry and the IR team are around today to answer any further questions. We wish you a good end of the week and enjoy the rest of the summer. Please stay safe out there. Thank you.

謝謝大家。感謝你今天多堅持了一會兒。Bob、Landry 和投資者關係團隊今天都在，可以回答任何其他問題。祝您週末愉快，享受餘下的夏日時光。請注意安全。謝謝。

This concludes today's conference call. Thank you for participating. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線了。