雷傑納榮製藥 (REGN) 2020 Q4 法說會逐字稿

Welcome to the Regeneron Pharmaceuticals Fourth Quarter 2020 Earnings Conference Call. My name is Michelle, and I'll be your operator for today's call. (Operator Instructions) Please note that this conference is being recorded.

歡迎參加再生元製藥公司2020年第四季財報電話會議。我是Michelle，將擔任本次電話會議的接線生。 （接線生說明）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。您可以開始了。

Thank you, Michelle. Good morning, good afternoon and good evening to everyone listening to the call today. Thank you for your interest in Regeneron Pharmaceuticals, and welcome to the Fourth Quarter 2020 Conference Call. An archive of this webcast will be available on our website.

謝謝米歇爾。各位早安、下午好、晚上好，歡迎收聽今天電話會議的各位。感謝您對再生元製藥的關注，歡迎參加2020年第四季電話會議。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, Executive Vice President and Head of Commercial; Bob Landry, Executive Vice President and Chief Financial Officer. After our prepared remarks, we will open the call for Q&A.

今天與我一同參加電話會議的有：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；執行副總裁兼商務主管瑪麗昂·麥考特；以及執行副總裁兼首席財務官鮑勃·蘭德里。在我們分別致詞後，我們將進入問答環節。

I would 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, 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 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-K for the year ended December 31, 2020, which we are planning to file with the SEC on Monday. Regeneron does not undertake any obligation to update any forward looking statements whether as a result of new information, future events or otherwise.

我想提醒各位，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、財務預測和指引、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、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該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，包括我們計劃於週一向美國證券交易委員會提交的截至2020年12月31日止年度的10-K表格。 Regeneron不承擔因新資訊、未來事件或其他原因而更新任何前瞻性聲明的義務。

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

此外，請注意，今天的電話會議將討論GAAP和非GAAP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。

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

通話結束後，鮑伯·蘭德里和投資者關係團隊將回答更多問題。

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 on today's call. 2020 was a devastating year for so many individuals and their families who succumbed to COVID-19. At Regeneron, we have done all we can to be part of the solution. And we'll spend quite a bit of time today trying to inform you of our efforts.

謝謝賈斯汀，也謝謝今天所有參加電話會議的各位。 2020年對許多人及其家庭來說是毀滅性的一年，他們因新冠肺炎去世。在再生元公司，我們竭盡所能，力求成為解決方案的一部分。今天，我們將花相當多的時間向大家介紹我們所做的努力。

On a more general note for the company that despite operating in unprecedented circumstances of a global pandemic, Regeneron delivered strong commercial and financial results while advancing our innovative R&D pipeline and joining the fight against COVID-19. Despite COVID-19, we never lost sight of our focus on the patients who count on us for our innovative medicines and novel medical break fees.

就公司整體而言，儘管面臨全球疫情這一前所未有的挑戰，Regeneron 依然取得了強勁的商業和財務業績，同時推進了創新研發管線，並積極投身抗擊新冠疫情的鬥爭。儘管受到新冠疫情的影響，我們始終不忘初心，關注那些信賴我們創新藥物和新型醫療優惠政策的患者。

For the full year 2020, we grew the top line by 30% and the bottom line by 28% with an increasingly diversified set of revenue and earnings streams. In fact, more than 80% of our top line growth came from products and revenues other than EYLEA.

2020年全年，我們的營收成長了30%，淨利潤成長了28%，這得益於收入和獲利來源的日益多元化。事實上，超過80%的營收成長來自安樂死以外的產品和收入。

EYLEA global net sales were nearly $8 billion and grew 5% compared to the prior year. In the U.S., sales were close to $5 billion and grew 7% versus the prior year, rebounding strongly from April lows due to COVID-19 and outperforming the broader anti-VEGF category. EYLEA's efficacy, safety and convenience creates a high bar for current and potential future entries, leaving us confident in its durability for years to come.

EYLEA全球淨銷售額接近80億美元，較去年同期成長5%。在美國，銷售額接近50億美元，年增7%，從4月受新冠疫情影響的低點強勁反彈，並跑贏了整個抗VEGF藥物市場。 EYLEA的高效性、安全性和便利性為現有及潛在的同類產品樹立了很高的標桿，我們對其未來多年的市場表現充滿信心。

Next, our growth was also fueled by Dupixent, which sold more than $4 billion globally and grew 75% compared to the prior year. In the U.S. alone, more than 1 million prescriptions for Dupixent were written. Only 6% of eligible U.S. patients have been treated with Dupixent to date, leaving much more room to grow. With regulatory approvals in atopic dermatitis, asthma and chronic rhinosinusitis with nasal polyposis and a late-stage development program across 8 additional disease types, Dupixent has the potential to transform the treatment of type 2 inflammatory diseases.

其次，Dupixent也推動了我們的成長。該產品全球銷售額超過40億美元，較上年成長75%。光是在美國，Dupixent的處方量就超過100萬張。迄今為止，僅有6%的美國符合資格的患者接受了Dupixent治療，這意味著市場仍有巨大的成長空間。 Dupixent已獲準用於治療異位性皮膚炎、氣喘和伴隨鼻息肉的慢性鼻竇炎，並且針對另外8種疾病類型正在進行後期研發，因此它有望徹底改變2型發炎性疾病的治療格局。

In oncology, we are pleased that Libtayo remains the #1 treatment in cutaneous squamous cell carcinoma. In 2020, global net sales were approximately $348 million, representing growth of 80% on further market penetration in the U.S. and from launches around the world.

在腫瘤領域，我們很高興地看到，Libtayo 仍然是治療皮膚鱗狀細胞癌的首選藥物。 2020 年，Libtayo 的全球淨銷售額約為 3.48 億美元，年增 80%，這得益於其在美國市場的進一步滲透以及在全球範圍內的新產品上市。

Beyond Libtayo, we are emerging as a leader in the development of novel bispecific and other antibody treatments. We now have 12 oncology bodies in clinical development. Our ability to create a variety of rational combinations using our VelociSuite antibody technologies positions us well to unlock the next wave of innovation in immuno-oncology.

除了Libtayo之外，我們在新型雙特異性抗體和其他抗體療法的研發領域也正迅速崛起，成為產業領導者。目前，我們有12個腫瘤治療計畫正處於臨床開發階段。憑藉VelociSuite抗體技術，我們能夠開發出多種合理的組合療法，這使我們能夠更好地引領免疫腫瘤學領域的下一波創新浪潮。

Regeneron also made strides against the infectious diseases in 2020 with the FDA approval of Inmazeb, a monoclonal antibody cocktail and the first ever treatment for Ebola virus infection. But nowhere has the power of R&D teams and technology has been more evident than in the discovery and development of our novel antibody cocktail against COVID-19, known as REGEN-COV. In just 10 months, we went from program inception to clinically demonstrating profound antiviral activity as well as reduction of medical visits, to receiving an emergency use authorization for REGEN-COV in the United States. Most recently, we showed promising data that suggests REGEN-COV reduces transmission of the virus and prevents infections in patients at high risk of contracting the virus.

2020年，再生元公司在對抗傳染病方面也取得了重大進展，其單株抗體雞尾酒療法Inmazeb獲得FDA批准，成為首個用於治療伊波拉病毒感染的藥物。然而，研發團隊與技術實力在研發新型抗COVID-19抗體雞尾酒療法REGEN-COV的過程中體現得淋漓盡致。短短10個月內，我們便完成了從計畫啟動到臨床驗證其顯著抗病毒活性並減少就診次數的整個過程，最終獲得了美國緊急使用授權。最近，我們公佈的令人鼓舞的數據表明，REGEN-COV能夠降低病毒傳播，並預防高風險族群的感染。

Importantly, we announced a new supply agreement with the United States government for an additional 1.25 million treatment doses for up to $2.6 billion. Finally, we secured a strategic partnership with Roche to manufacture and commercialize REGEN-COV globally. These achievements would not have been possible without decades of investment in our innovative antibody-related technologies and our scientific talent, who are a continual source of pride.

值得一提的是，我們宣布與美國政府達成一項新的供應協議，將額外提供125萬劑治療藥物，價值高達26億美元。此外，我們還與羅氏公司建立了策略合作夥伴關係，在全球範圍內生產和銷售REGEN-COV。如果沒有數十年來對創新抗體相關技術和科研人才的持續投入，這些成就都將無法實現，而我們的科學研究人才也始終是我們引以為傲的來源。

Regeneron also completed shareholder-friendly actions in 2020, including restructuring our Praluent agreement with Sanofi and achieving profitability for the brand in the United States. We also executed the largest-ever United States health care equity offering with Sanofi's stake in our company. We leveraged our strong balance sheet and historically low interest rates to repurchase $5 billion of those shares, immediately reducing uncertainty and creating significant accretion for our shareholders.

2020年，Regeneron也採取了一系列有利於股東的舉措，包括重組與賽諾菲的Praluent協議，並實現了該品牌在美國的盈利。此外，我們也完成了美國醫療保健產業有史以來規模最大的股權發行，出售了賽諾菲持有的我公司股份。我們利用自身強勁的資產負債表和歷史低利率環境，回購了價值50億美元的股份，立即降低了不確定性，並為股東創造了顯著的收益成長。

We are entering 2021 with strong momentum across our entire business. We expect a number of exciting catalysts this year, including a series of important launches for Libtayo in lung cancer and basal cell cancers; Dupixent data readouts and launches; and milestones for other products that will further enhance our diversity of earnings and position us for sustained financial growth.

我們帶著強勁的業務發展勢頭邁入2021年。我們預計今年將迎來一系列令人振奮的利好因素，包括Libtayo在肺癌和基底細胞癌領域的一系列重要上市；Dupixent的數據解讀和上市；以及其他產品的里程碑事件，這些都將進一步豐富我們的盈利來源，並為我們實現持續的財務增長奠定基礎。

We are encouraged by the progress we are making against COVID-19 and expect several near-term data readouts for our antibody cocktail that George will outline momentarily. Importantly, our pipeline continues to grow and advance across a wide variety of diseases. Our core business momentum, new launches and R&D advances positions Regeneron, to deliver significant and sustained growth for years to come.

我們對抗擊新冠肺炎疫情的進展感到鼓舞，並預計近期將公佈我們抗體雞尾酒療法的幾項數據，喬治稍後將對此進行概述。重要的是，我們的研發管線在多種疾病領域持續成長與前進。核心業務的強勁勢頭、新產品的上市以及研發方面的進展，使再生元公司在未來幾年內能夠實現顯著且持續的成長。

Now I will turn the podium over to George.

現在我將把講台交給喬治。

Thank you, Len. While the world -- with the world still in the throes of the COVID-19 pandemic, I will start with our efforts on REGEN-COV, our antibody cocktail targeting the SARS-CoV-2 virus. Over the last few months, we have achieved several important milestones.

謝謝你，Len。雖然世界仍深陷新冠肺炎疫情的泥潭，但我首先要談談我們研發的抗體雞尾酒療法REGEN-COV，它針對的是SARS-CoV-2病毒。在過去的幾個月裡，我們取得了幾個重要的里程碑。

On November 21, our antibody cocktail received FDA emergency use authorization for recently diagnosed, mild to moderate COVID-19 in high-risk patients. The EUA was granted based on the initial results in patients from our large study in the non-hospitalized setting.

11月21日，我們的抗體雞尾酒療法獲得FDA緊急使用授權，用於治療近期確診的輕度至中度新冠肺炎高風險患者。此緊急使用授權是基於我們一項大型非住院患者研究的初步結果而授予的。

In December, we announced encouraging initial REGEN-COV results in hospitalized patients on low flow oxygen, with the cocktail treatment successfully passing futility criteria to continue and being associated with the reduction in the risk of death or mechanical ventilation.

去年 12 月，我們宣布了 REGEN-COV 在低流量吸氧住院患者中令人鼓舞的初步結果，該混合療法成功通過了繼續治療的無效性標準，並與降低死亡或機械通氣風險相關。

Just last month, we released initial data with REGEN-COV in the prevention setting, which showed 100% prevention of symptomatic COVID-19 infections and 100% reduction of the duration of high viral shedding, when patients would be expected to be most infectious and capable of transmitting the virus.

就在上個月，我們發布了 REGEN-COV 在預防方面的初步數據，結果顯示，該藥物可 100% 預防 COVID-19 症狀感染，並 100% 縮短病毒高脫落期的持續時間，而患者在高病毒脫落期通常最具傳染性，最容易傳播病毒。

Importantly, these results were achieved using our lower subcutaneous dose, which should simplify delivery. We expect important additional readouts over the next few months in terms of confirmatory Phase III results in the prevention setting; in the outpatient setting, which includes an evaluation of our lower dose; and in the hospitalized setting as part of our collaboration with the U.K. RECOVERY study. These upcoming data sets are important for demonstrating efficacy across broader patient populations and supporting regulatory approvals worldwide.

重要的是，這些結果是在我們採用較低皮下劑量的情況下取得的，這將簡化給藥流程。我們預計在未來幾個月內將獲得更多重要的數據，包括預防性治療、門診治療（包括對較低劑量的評估）以及住院治療（作為我們與英國RECOVERY研究合作的一部分）等方面的III期臨床試驗驗證結果。這些即將發布的數據集對於證明藥物在更廣泛的患者群體中的療效以及支持全球監管部門的批准至關重要。

I want to address the important issue of emerging virus variants which have dominated the news as they have the potential to evade both natural as well as vaccine-derived immunity. We had prospectively designed our cocktail with such variants in mind. In fact, as we published in Science Journal back in June, we anticipated the exact mutation that is raising concerns about resistance for the South African and Brazilian variants that have now also been seen in the United States. Because of our prospective recognition of the threats of variants in our intelligent design approach, our current antibody cocktail is active against all these currently known virus variants as was recently independently confirmed multiple prominent academics. If needed, we also have a large antibody collection that could be ready to mix and match in new cocktails against potential future viral variants.

我想談談病毒變異株不斷湧現這一重要問題，它們之所以成為新聞熱點，是因為它們有可能逃避自然免疫和疫苗免疫。我們在設計抗體雞尾酒療法時，就考慮到了這些變異株。事實上，正如我們六月在《科學》雜誌上發表的文章所述，我們預測到了引發人們對南非和巴西變異株抗藥性擔憂的確切突變，而這些變異株現在也出現在美國。由於我們透過智慧設計方法預先認識到了變異株的威脅，我們目前的抗體雞尾酒療法對所有已知的病毒變異株都有效，這一點最近也得到了多位知名學者的獨立證實。如有需要，我們也擁有龐大的抗體庫，可以隨時混合搭配，研發出針對未來潛在病毒變異株的新型抗體雞尾酒療法。

We of course hope that vaccines will efficiently and rapidly create widespread immunity and this immunity will withstand the challenge of time and of emerging variants. However, even if the vaccine successfully provide widespread and long-lasting immunity according to the most optimistic time line, it is estimated that up to hundreds of thousands of individuals may tragically die until we reach that point. Moreover, emerging variants are posing a very real threat to both natural and vaccine-derived immunity. Recent data indicate vaccines may already be less than 50% effective against the new variants, with new mutations having the potential to further undermine vaccine immunity.

我們當然希望疫苗能夠有效率且快速地建立起廣泛的免疫力，而這種免疫力能夠經得起時間的考驗和新出現的變異株的挑戰。然而，即便按照最樂觀的時間表，疫苗能夠成功提供廣泛且持久的免疫力，據估計，在達到這一目標之前，仍有數十萬人可能因此不幸喪生。此外，新出現的變異株對自然免疫和疫苗誘發的免疫都構成了切實的威脅。最新數據顯示，疫苗對新出現的變異株的有效率可能已經低於50%，而新的突變有可能進一步削弱疫苗的免疫力。

We believe strategic deployment of antibody approaches, such as our REGEN-COV antibody cocktail, could be targeted in such a way so as to reduce the loss of life over the next 6 months as well as to provide protection against the possibility of waning vaccine efficacy and ongoing disease prevalence.

我們相信，策略性地部署抗體療法，例如我們的 REGEN-COV 抗體混合物，可以有針對性地減少未來 6 個月的生命損失，並防止疫苗效力減弱和疾病持續流行。

Moving to Dupixent in our immunology and inflammation portfolio. Dupixent is a new -- Dupixent has multiple trials and new potential indications that are progressing quickly. Most notably, our Phase III trial in eosinophilic esophagitis is now fully enrolled. Recall that we presented encouraging data from Part A of this study last year.

接下來，我們將重點放在免疫學和發炎產品組合中的Dupixent。 Dupixent是一種新型藥物，目前正在進行多項臨床試驗，並探索新的潛在適應症，這些進展都非常迅速。尤其值得一提的是，我們針對嗜酸性食道炎的III期臨床試驗已完成全部受試者招募。回顧一下，我們去年公佈了該研究A部分的令人鼓舞的數據。

As we outlined recently, Dupixent is also part of our two-pronged approach against chronic obstructive pulmonary disease, or COPD, along with itepekimab, our anti IL-33 antibody. The 2 Dupixent Phase III studies in type 2 COPD are ongoing and enrolling patients. Based on our proof-of-concept Phase II data that will be published later this year, we believe that blocking IL-33 could be useful for treating COPD in former smokers, where we have seen a 40% reduction in exacerbations.

正如我們近期所述，Dupixent 與我們研發的抗 IL-33 抗體 itepekimab 共同構成了我們對抗慢性阻塞性肺病 (COPD) 的雙管齊下療法。目前，兩項針對 2 型 COPD 的 Dupixent III 期臨床試驗正在進行中，並已開始招募患者。基於我們即將於今年稍後公佈的概念驗證性 II 期臨床試驗數據，我們認為阻斷 IL-33 可能有助於治療既往吸菸者的 COPD，我們已觀察到該療法可使 COPD 急性加重次數減少 40%。

We and Sanofi have now started the first Phase III study of itepekimab in this subset of COPD patients with a confirmatory Phase III study to begin imminently. Our hope for this broad program is that Dupixent and itepekimab can provide real benefit for the many patients suffering from COPD and with no biologics options to date.

我們和賽諾菲現已啟動首個針對特定慢性阻塞性肺病（COPD）患者的itepekimab III期臨床研究，一項確證性III期臨床研究也即將啟動。我們希望這項廣泛的研究計畫能讓Dupixent和itepekimab真正造福眾多目前尚無生物製劑治療的COPD患者。

Dupixent is also part of multiple additional approaches to treat allergic diseases, in particular, in so-called efforts to desensitize individuals from food and inhaled allergens. As you know, millions are undergoing allergy desensitization each year, often with unsatisfying results even after years of allergy treatments. I am pleased to announce that the Phase II placebo-controlled trial of pediatric patients with peanut allergy met its primary and key secondary endpoints, showing that Dupixent, in combination with Aimmune Therapeutics' oral immunotherapy, significantly improved desensitization to peanut protein when compared to oral immunotherapy alone. These results, coupled with data later this year from a separate Phase II trial of Dupixent therapy in patients with peanut allergy, will inform next steps in this setting and for other forms of allergy desensitization as well.

Dupixent也是多種其他過敏性疾病治療方法的一部分，尤其是在所謂的食物和吸入性過敏原脫敏治療中。眾所周知，每年有數百萬人接受過敏脫敏治療，但即使經過多年的治療，效果往往也不盡如人意。我很高興地宣布，針對花生過敏兒童患者的II期安慰劑對照試驗達到了其主要終點和關鍵次要終點，結果表明，與單獨使用口服免疫療法相比，Dupixent聯合Aimmune Therapeutics的口服免疫療法顯著提高了對花生蛋白的脫敏效果。這些結果，加上今年稍後公佈的另一項針對花生過敏患者的Dupixent治療II期試驗的數據，將為該領域以及其他形式的過敏脫敏治療的後續步驟提供指導。

We also have additional groundbreaking new approaches to allergy. We have created the first antibody-based therapeutics directed to allergens themselves with the idea that these antibodies can directly bind and neutralize the allergens. Our first 2 anti-allergy antibodies target cat allergy and birch allergy with birch being the major cause of seasonal allergies in the spring. And the therapies may be particularly important for patients with these and other allergies with concomitant asthma since these patients are not candidates for allergy desensitization.

我們還擁有其他突破性的過敏治療新方法。我們研發了首批針對過敏原本身的抗體療法，概念是這些抗體可以直接結合併中和過敏原。我們首批兩種抗過敏抗體分別針對貓過敏和樺樹過敏，樺樹是春季季節性過敏的主要致敏物。對於患有此類過敏症以及其他伴隨氣喘的過敏症患者而言，這些療法可能特別重要，因為這些患者不適合接受減敏治療。

We will be presenting detailed data from proof-of-concept studies at upcoming meetings showing that these anti-allergen antibodies have the potential to revolutionize the treatment paradigm. And our first Phase III field study in birch allergy is now open for enrollment and will be conducted throughout the allergy season, with results expected later this year. We are similarly planning a Phase III study in patients suffering from cat allergy to begin later this year.

我們將在即將舉行的會議上公佈概念驗證研究的詳細數據，這些數據表明，這些抗過敏抗體有望徹底改變目前的治療模式。我們首個針對樺樹過敏的III期臨床試驗現已開始招募患者，並將於整個過敏季期間進行，預計今年稍後公佈結果。同樣，我們也計劃於今年稍後啟動一項針對貓過敏患者的III期臨床試驗。

Next, I'd like to briefly discuss EYLEA. We appreciate that EYLEA has withstood myriad attempts to challenge its leading efficacy and safety profile over the last decade as we have accumulated a real-world experience of over 30 million injections. And it is not clear that any near-term competitors have data suggesting important advantages. We would like to remind you that clinical trials have shown that substantial numbers of patients can be effectively treated at longer intervals with EYLEA. For example, the ALTAIR study shows that about 40% of patients can be extended to a 16-week treatment interval. We are now enrolling our Phase III program with high-dose EYLEA, which we hope can deliver the same efficacy and safety to allow even more patients to be extended.

接下來，我想簡單談談EYLEA。我們深知，在過去十年中，EYLEA憑藉其領先的療效和安全性，經受住了無數挑戰，積累了超過3000萬次注射的真實世界經驗。目前尚不清楚近期是否有任何競爭對手的數據顯示其具有顯著優勢。我們想提醒各位，臨床試驗表明，大量患者可以使用EYLEA進行有效治療，且治療間隔可以延長。例如，ALTAIR研究表明，約40%的患者可以將治療間隔延長至16週。我們目前正在進行高劑量EYLEA的III期臨床試驗，希望該試驗能維持相同的療效和安全性，使更多患者能夠延長治療間隔。

Moving to our oncology efforts, and starting with Libtayo. In a matter of weeks, assuming positive FDA action, we expect 2 significant label expansions for Libtayo in non-small cell lung cancer and in basal cell carcinoma. Later this year, the independent data safety monitoring committee will be conducting interim analyses for our Libtayo-chemotherapy combination study in lung cancer from -- and for a monotherapy study in second-line cervical cancer. We continue to make progress with Libtayo as it is establishing itself as the leading immunotherapy for non-melanoma skin cancers, as we hope to make it a potential major new player in the lung cancer space and as we employ it as a foundational therapy to our oncology strategy for bringing novel combinations to the many cancers that are desperate for new treatments.

接下來談談我們在腫瘤領域的進展，首先是Libtayo。假設FDA批准，我們預期Libtayo將在幾週內獲得兩個重要的適應症擴展，分別用於非小細胞肺癌和基底細胞癌。今年晚些時候，獨立資料安全監測委員會將對我們Libtayo合併化療治療肺癌的研究以及Libtayo單藥治療二線子宮頸癌的研究進行中期分析。 Libtayo正逐步成為非黑色素瘤皮膚癌領域領先的免疫療法，我們希望它能成為肺癌領域的重要新成員，並將其作為我們腫瘤治療策略的基礎療法，為眾多亟需新療法的癌症患者帶來創新的聯合療法。

This combination approach has a major focus on our bispecifics portfolio as we are emerging as leaders with both our CD3 classes bispecifics as well as our so-called costim bispecifics. These 2 classes of bispecifics can be paired with each other as well as with Libtayo, and we are exceeding all these combinations and more.

這種組合策略主要著重於我們的雙特異性抗體產品組合，因為我們在CD3類雙特異性抗體和所謂的costim雙特異性抗體方面都處於領先地位。這兩類雙特異性抗體可以相互組合，也可以與Libtayo組合，而且我們在所有這些組合中都表現出色，甚至超越了預期。

We presented update at the American Society of Hematology, or ASH meeting, in December on odronextamab, our CD20xCD3 bispecific, which continued to show high rates of durable responses in follicular and diffuse large B-cell lymphomas. We are working with the FDA update to determine the optimal dosing program protocol designed to further minimize already rare cytokine release syndrome events during the step-up dosing phase of this powerful agent. A subcutaneous formulation is under development as well.

我們在12月舉行的美國血液學會（ASH）年會上報告了我們的CD20xCD3雙特異性抗體odronextamab的最新進展。此抗體在濾泡性淋巴瘤和瀰漫性大B細胞淋巴瘤中持續顯示出較高的持久緩解率。我們正與FDA合作，制定最佳給藥方案，旨在進一步降低此強效藥物在劑量遞增階段發生細胞激​​素釋放症候群的機率（此症候群的發生率本來就很低）。此外，我們也正在研發皮下製劑。

We also provided updates at ASH on our BCMAxCD3 bispecific for relapsed/refractory myeloma. And our pivotal Phase II trial is enrolling well with full enrollment anticipated this year. Phase III trials for this program as well, as studies of a subcutaneous formulation, are also on track to start this year as well.

在ASH會議上，我們也報告了我們針對復發/難治性多發性骨髓瘤的BCMAxCD3雙特異性抗體的最新進展。我們的關鍵性II期臨床試驗正在順利進行，預計今年將完成全部入組。該計畫的III期臨床試驗，即皮下製劑的研究，也正按計畫進行，預計今年啟動。

Our third CD3 bispecific in the clinic, REGN4018, our MUC16xCD3 bispecific, continues in dose-escalation trials for ovarian cancer where we are observing early efficacy signals.

我們第三款進入臨床的 CD3 雙特異性抗體 REGN4018，即 MUC16xCD3 雙特異性抗體，正在繼續進行卵巢癌的劑量遞增試驗，我們觀察到了早期療效訊號。

Our costim bispecifics are also progressing. Notably, our trial for our MUC16xCD28 costimulatory bispecific has just dosed its first patient and will continue in combination with Libtayo. Later this year, it will also be combined in patients with our MUC16xCD3 bispecific, making it our first clinical pairing of CD3 in costim bispecifics, which we hope will provide for a game-changing and generalizable approach to solid as well as hematologic tumors. Regarding the latter, we will soon be initiating trials of a costim bispecific to be paired with our CD20xCD3 bispecific for lymphoma; and later this year, of a different costim bispecific to be paired with our BCMAxCD3 bispecific in myeloma. Our [PCMA] costim bispecific is progressing in dose-escalation trials with Libtayo for patients with prostate cancer. And we also have a costim targeting the EGF receptor that will allow for a variety of novel combinations as well.

我們的共刺激雙特異性抗體也在取得進展。值得注意的是，我們的MUC16xCD28共刺激雙特異性抗體的臨床試驗剛剛完成了首例患者的給藥，並將繼續與利妥昔單抗（Libtayo）聯合使用。今年晚些時候，該抗體也將與我們的MUC16xCD3雙特異性抗體聯合用於患者，這將是我們首次將CD3與共刺激雙特異性抗體進行臨床聯合應用，我們希望這將為實體瘤和血液腫瘤提供一種具有變革意義且可推廣的治療方法。關於後者，我們即將啟動一項針對淋巴瘤的共刺激雙特異性抗體與CD20xCD3雙特異性抗體聯合使用的臨床試驗；今年晚些時候，還將啟動一項針對多發性骨髓瘤的臨床試驗，該試驗將使用另一種共刺激雙特異性抗體與BCMAxCD3雙特異性抗體聯合使用。我們的[PCMA]共刺激雙特異性抗體正在與利妥昔單抗聯合用於前列腺癌患者的劑量遞增試驗中取得進展。此外，我們還有一種針對EGF受體的共刺激抗體，將使我們能夠開發出多種新的聯合療法。

These combination programs pairing bispecs with each other and with our anti-PD-1 has the potential synergistically unleash the power of immuno-oncology more broadly than currently approved treatments. And thus, there is a lot of interest in the timing of the data releases from these early combination programs. We hope you appreciate the requirement for careful and deliberate dose escalation trials to ensure patient safety as these drugs are designed to activate patients' immune systems and involve novel and powerful pathways. Hence, while early results or top line data announcements are possible in 2021, readouts are equally possible to occur in 2022.

這些將雙特異性抗體相互結合，並與我們的抗PD-1抗體聯合使用的聯合療法，預計將比目前已批准的療法更廣泛地發揮免疫腫瘤學的協同作用。因此，人們對這些早期聯合療法的數據發佈時間非常關注。我們希望您瞭解，由於這些藥物旨在激活患者的免疫系統並涉及新型且強大的通路，因此需要進行謹慎周密的劑量遞增試驗，以確保患者安全。因此，雖然2021年有可能公佈早期結果或初步數據，但2022年也同樣有可能公佈。

Beyond oncology, I would like to highlight that next week, we expect approval for evinacumab, now known as Evkeeza, for homozygous familial hypercholesterolemia. If approved, this addition to our portfolio builds upon our cardiometabolic expertise and has the potential to help patients suffering from this rare disease.

除了腫瘤領域，我還想重點介紹一下，我們預計下週evinacumab（現更名為Evkeeza）將獲準用於治療純合子家族性高膽固醇血症。如果獲批，這項新藥將進一步鞏固我們在心血管代謝領域的專長，並有望幫助患有這種罕見疾病的患者。

Before I finish, I'd like to highlight that we continue to invest in our world-leading human sequencing efforts at the Regeneron Genetics Center, which is pivotal to identifying and validating targets for our new genetics medicines initiative, which we believe could be transformational not only for Regeneron, but for our entire industry and already involves important collaborations with partners such as Alnylam, Intellia, Decibel, bluebird and others.

在結束之前，我想強調，我們將繼續投資於 Regeneron 遺傳學中心的世界領先的人類測序工作，這對於識別和驗證我們新的基因藥物計劃的靶點至關重要。我們相信，這項計劃不僅對 Regeneron，而且對整個行業可能具有變革性意義，並且已經與 Alnylam、Intellia、Decibel、bluebird 等合作夥伴開展了重要的合作。

To conclude, in 2020, we and our partners have introduced 9 new investigational therapies into the clinic, submitted marketing applications for 6 new indications and secured 2 new drug approvals or authorizations. We are proud of the remarkable accomplishments our Regeneron team has achieved in a difficult year, and we thank our many investigators and patients who have been essential to helping us with these accomplishments.

總之，2020年，我們及合作夥伴已將9種新的在研療法推向臨床，提交了6項新適應症的上市申請，並獲得了2項新藥的批准或授權。我們為Regeneron團隊在充滿挑戰的一年中取得的卓越成就感到自豪，並衷心感謝眾多研究人員和患者，他們的支持對我們取得這些成就至關重要。

With that, I'd like to turn it over to Marion.

接下來，我想把麥克風交給瑪莉安。

Thank you, George. We ended 2020 with positive momentum across our commercial portfolio as our core products, EYLEA, Dupixent and Libtayo, delivered strong performance in the fourth quarter. Our 2020 results, coupled with near-term launch opportunities, position us for continued diversified growth in 2021.

謝謝喬治。 2020 年末，我們的商業產品組合整體呈現積極成長勢頭，核心產品安理國際 (EYLEA)、度普利 (Dupixent) 和利必妥 (Libtayo) 在第四季度表現強勁。 2020 年的業績，加上近期即將推出的新產品，為我們 2021 年持續多元化成長奠定了基礎。

Beginning with EYLEA. Fourth quarter global net sales grew 10% year-over-year to $2.2 billion. As we reported last month, U.S. EYLEA net sales grew 10% year-over-year to $1.34 billion, the highest reported net sales since EYLEA's launch. EYLEA again outperformed the category with share gains from both branded and unbranded competition. EYLEA share of the branded category approached 75% for the quarter and EYLEA remains the #1 prescribed anti-VEGF therapy overall in wet AMD and diabetic eye disease. While volume in the overall anti-VEGF category declined in 2020, EYLEA was the only product in the category to grow. Patient volumes are now normalizing. EYLEA sets a high bar on efficacy, safety, dosing flexibility and real-world experience for current and future competition.

首先來看EYLEA。第四季全球淨銷售額年增10%，達22億美元。正如我們上月報道，EYLEA在美國的淨銷售額年增10%，達到13.4億美元，創下EYLEA上市以來的最高淨銷售額紀錄。 EYLEA再次超越同類產品，市佔率從品牌藥和非品牌藥競爭中均有所成長。本季EYLEA在品牌藥市場的佔有率接近75%，且仍是濕性AMD和糖尿病眼疾領域處方量排名第一的抗VEGF療法。儘管2020年抗VEGF藥物整體銷售量有所下降，但EYLEA是該類別中唯一成長的產品。目前患者數量正在恢復正常。 EYLEA在療效、安全性、給藥靈活性和真實世界經驗方面為當前和未來的競爭對手樹立了高標準。

The anti-VEGF category continues to be supported by the aging population and increasing prevalence of diabetes. Realizing the full potential in diabetic eye disease remains a key initiative, representing a significant growth opportunity for EYLEA and is largely unpenetrated. We intend to initiate a direct-to-consumer campaign to create awareness for patients on the importance of vision care as part of managing their diabetes. In summary, EYLEA had an impressive quarter, and we remain confident in its outlook.

抗VEGF藥物市場持續受益於人口老化和糖尿病盛行率的上升。充分發揮抗VEGF藥物在糖尿病眼部疾病治療領域的潛力仍然是一項關鍵舉措，這為EYLEA帶來了巨大的成長機遇，而目前該領域尚未充分開發。我們計劃發起一項面向消費者的直接行銷活動，以提高患者對視力保健在糖尿病管理中重要性的認識。總而言之，EYLEA本季業績斐然，我們對公司前景充滿信心。

Next, we recorded $146 million for our antibody cocktail, REGEN-COV, in the fourth quarter. Where appropriate, we are deploying commercial efforts under the EUA to improve availability for this important treatment against COVID-19 for at-risk patients. We are engaging with all stakeholders to reduce bottlenecks and drive utilization rates higher. Regeneron is working to educate stakeholders, including patients, on the urgency to treat at-risk nonhospitalized patients within 10 days of receiving a positive COVID-19 diagnosis. Initiatives to reduce administrative burden and direct patients to treatment centers are beginning to yield encouraging results. Physicians using REGEN-COV are providing very positive feedback on treatment results.

其次，我們的抗體雞尾酒療法 REGEN-COV 在第四季度實現了 1.46 億美元的收入。在適當情況下，我們將根據緊急使用授權 (EUA) 進行商業推廣活動，以提高高風險患者獲得此重要 COVID-19 療法的途徑。我們正與所有利害關係人合作，以減少瓶頸並提高使用率。再生元公司正努力向包括患者在內的利益相關者普及相關知識，強調在 COVID-19 檢測呈陽性後 10 天內對高風險非住院患者進行治療的緊迫性。旨在減輕行政負擔和引導患者前往治療中心的措施已開始取得令人鼓舞的成果。使用 REGEN-COV 的醫生對治療效果給予了非常正面的回饋。

Let me also briefly discuss another new medicine, evinacumab, brand name Evkeeza. We're prepared for the February 11 PDUFA date for Evkeeza for the treatment of HoFH, a rare disease that affects approximately 1,300 patients in the U.S. There's high unmet need for these patients with this rare genetic condition as they struggle to keep their LDL-cholesterol levels under control. These patients face an increased risk of premature heart disease as early as their teenage years. We are leveraging our cardiometabolic expertise and existing commercial platform to drive uptake in this rare disease category.

我還想簡單介紹一下另一種新藥——evinacumab，商品名為Evkeeza。我們已做好準備，迎接Evkeeza於2月11日提交的PDUFA申請，用於治療純合子家族性高膽固醇血症（HoFH）。 HoFH是一種罕見疾病，在美國約有1300名患者。這些患有罕見遺傳疾病的患者，由於難以控制低密度脂蛋白膽固醇（LDL-C）水平，存在著巨大的未滿足醫療需求。這些患者早在青少年時期就面臨早發性心臟病的風險。我們將利用我們在心血管代謝領域的專業知識和現有的商業平台，推動Evkeeza在這一罕見疾病領域的應用。

Turning now to Libtayo, where fourth quarter global net sales grew to $97 million. In the U.S., net sales were $74 million, driven by steady volume growth in advanced CSCC. We are nearing the potential approval of 2 additional indications for Libtayo in basal cell carcinoma and non-small cell lung cancer, both of which received priority reviews and have upcoming PDUFA dates. Our teams are eager and ready to launch once approved.

接下來談談Libtayo，第四季全球淨銷售額成長至9,700萬美元。在美國，淨銷售額為7,400萬美元，主要得益於晚期皮膚鱗狀細胞癌（CSCC）銷量的穩定成長。 Libtayo在基底細胞癌和非小細胞肺癌這兩項適應症的審批也即將完成，這兩項適應症均已獲得優先審查資格，並即將確定處方藥用戶付費法案（PDUFA）的審批日期。我們的團隊已做好充分準備，一旦獲準即可立即上市。

For basal cell carcinoma, there are no FDA-approved treatment options once the patient progresses on or becomes intolerant to Hedgehog inhibitors. Just as we did with CSCC, we will work to establish Libtayo as the standard of care in appropriate BCC patients.

對於基底細胞癌，一旦患者對 Hedgehog 抑制劑產生抗藥性或病情進展，目前尚無 FDA 核准的治療方案。正如我們之前對皮膚鱗狀細胞癌所做的那樣，我們將努力使 Libtayo 成為合適的基底細胞癌患者的標準治療方案。

We also look forward to competing in non-small cell lung cancer, where there's a large opportunity among patients with PD-L1 expressions at least 50%. Libtayo has a favorable product profile, and a growing majority of treatment centers and oncologists have experienced using Libtayo in their CSCC patients. Physicians prefer choice, and recent market research shows that nearly 2/3 of physicians are highly motivated to evaluate Libtayo for their lung cancer patients, if approved.

我們也期待在非小細胞肺癌領域展開競爭，PD-L1表達至少50%的患者群體蘊藏著巨大的市場機會。 Libtayo擁有良好的產品特性，越來越多的治療中心和腫瘤科醫生已在皮膚鱗狀細胞癌（CSCC）患者中使用過Libtayo。醫生傾向於擁有更多選擇，近期市場調查顯示，如果Libtayo獲得批准，近三分之二的醫生非常願意評估其在肺癌患者中的應用。

Additionally, we've built a highly experienced commercialization team with significant launch experience with this class. If approved, we aim to rapidly increase market awareness of Libtayo as a compelling new anti-PD-1 monotherapy treatment option.

此外，我們組建了一支經驗豐富的商業化團隊，在該類藥物的上市方面擁有豐富的經驗。如果獲得批准，我們的目標是迅速提高市場對Libtayo的認知度，使其成為一種極具吸引力的新型抗PD-1單藥治療方案。

Finally, moving to Dupixent. Global net sales in the fourth quarter were $1.17 billion, representing 56% growth compared to the prior year. In the U.S., broad-based growth across all approved indications contributed to net sales of $926 million. We continue to see strong prescription trends across all approved indications, and weekly new patient shares have recently eclipsed pre-pandemic levels.

最後，我們來看看Dupixent。第四季全球淨銷售額為11.7億美元，較去年同期成長56%。在美國，所有核准適應症的全面成長貢獻了9.26億美元的淨銷售額。我們持續看到所有核准適應症的處方量呈現強勁成長趨勢，每週新增病患份額近期已超過疫情前水準。

Atopic dermatitis, the largest indication, is a significant driver on Dupixent's rapid onset, proven efficacy and well-established safety profile. Physicians continue to expand prescribing across both moderate and severe disease and in younger populations where safety is paramount. Despite the impressive launch growth trajectory, there remains significant opportunity as only a small percentage of the over 2 million biologic-eligible patients in the U.S. have been prescribed Dupixent. Our initiatives aim to grow new patient starts as there is substantial opportunity for many more patients to benefit and support patients already on Dupixent to continue their treatment.

異位性皮膚炎是Dupixent最大的適應症，也是其快速起效、療效確切且安全性良好的重要驅動因素。醫生們正不斷擴大Dupixent的處方範圍，涵蓋中重度異位性皮膚炎患者以及對安全性要求極高的年輕族群。儘管Dupixent上市後的成長勢頭令人矚目，但仍存在巨大的發展空間，因為在美國超過200萬符合生物製劑治療條件的患者中，只有一小部分人接受了Dupixent治療。我們的各項措施旨在增加新患者的使用，因為有巨大的機會讓更多患者受益，同時也支持已接受Dupixent治療的患者繼續他們的治療。

Moving to asthma. Dupixent is performing well in this competitive market based on its clinical efficacy and safety profile, which is compelling and differentiated to prescribers. Our market expansion efforts supporting HCPs and patients, including DTC, continue to have a meaningful impact on new initiations. And launch preparations are underway in pediatric -- in the pediatric asthma setting.

接下來是氣喘治療。 Dupixent憑藉其卓越的臨床療效和安全性，在這個競爭激烈的市場中表現出色，其優勢對處方醫生而言極具吸引力且獨具特色。我們為醫療保健專業人員和患者提供的市場拓展支持，包括直接面向消費者的推廣，持續對新發病例產生顯著影響。此外，兒科氣喘領域的上市準備工作也緊鑼密鼓地進行中。

For chronic rhinosinusitis with nasal polyps, we see healthy demand and continued strong prescribing trends among ENTs and allergists. Dupixent is core to our diversified growth strategy, where there remains substantial opportunity for future expansion.

對於伴有鼻息肉的慢性鼻竇炎，我們看到耳鼻喉科醫生和過敏科醫生對該藥物的需求旺盛，處方量持續強勁。 Dupixent 是我們多元化成長策略的核心，未來仍有龐大的擴張空間。

In closing, we ended 2020 with momentum, delivering strong performance across our business. With several near-term launches ahead, we have important opportunities to strengthen our thriving commercial portfolio and capitalize on growth.

綜上所述，我們以強勁的勢頭結束了2020年，各項業務均取得了優異的業績。隨著近期多項新產品的推出，我們擁有重要的機會來加強我們蓬勃發展的商業產品組合，並充分利用成長潛力。

Now I'll turn the call to Bob.

現在我把電話轉給鮑伯。

Thanks, Marion, and good morning and good afternoon, everybody. My comments today on financial results and outlook will be on a non-GAAP basis where applicable. For the fourth quarter of 2020, Regeneron delivered again double-digit broad-based top and bottom line growth. Our revenue streams continue to diversify with significant growth contributions from Dupixent and REGEN-COV as we invest in our best-in-class pipeline for sustained future growth.

謝謝 Marion，大家早安/下午好。今天我對財務表現和展望的評論將盡可能採用非公認會計準則 (non-GAAP)。 2020 年第四季度，Regeneron 再次實現了兩位數的營收和利潤全面成長。隨著我們增加對一流研發管線的投資，以實現未來持續成長，Dupixent 和 REGEN-COV 為我們帶來了顯著的成長貢獻，我們的收入來源也持續多元化。

For the fourth quarter, total revenue grew 30% year-over-year to $2.4 billion driven by: Growth in U.S. EYLEA sales; higher collaboration revenues from our partners, Sanofi and Bayer; and sales of our REGEN-COV antibody cocktail. Diluted net income per share grew 27% year-over-year to $9.53 on net income of $1.1 billion.

第四季度，總營收年增30%至24億美元，主要得益於：美國安永（EYLEA）銷售額的成長；來自合作夥伴賽諾菲和拜耳的合作收入增加；以及REGEN-COV抗體雞尾酒療法的銷售。稀釋後每股淨收益年增27%至9.53美元，淨利為11億美元。

Since Marion discussed our U.S. EYLEA results, I will start with our Bayer and Sanofi collaborations, starting with the Bayer collaboration.

既然 Marion 已經討論了我們在美國 EYLEA 的成果，那我就先從我們與拜耳和賽諾菲的合作說起，先從拜耳的合作說起。

Ex-U.S. EYLEA net product sales reported to us by Bayer were $859 million for the fourth quarter of 2020, representing growth of 10% on a reported basis compared to the prior year. Total Bayer collaboration revenue was $361 million, of which we recorded $335 million for our share of net profits from EYLEA sales outside the U.S.

拜耳向我們報告稱，2020 年第四季美國以外地區 EYLEA 淨產品銷售額為 8.59 億美元，按報告基準計算，較上年同期增長 10%。拜耳合作總收入為 3.61 億美元，其中我們確認了 3.35 億美元，這是我們應得的美國以外地區 EYLEA 銷售淨利潤份額。

Total Sanofi collaboration revenue was $317 million in the fourth quarter. Our share of the profits from the commercialization of non-IO antibodies was $230 million, which compares favorably to profits of $104 million in the prior year. This growth was primarily driven by higher Dupixent profits.

第四季度，賽諾菲合作總收入為3.17億美元。我們從非免疫腫瘤抗體商業化中獲得的利潤份額為2.3億美元，較上年同期的1.04億美元有所增長。這一增長主要得益於Dupixent利潤的提高。

Other revenue increased to $123 million in the fourth quarter of 2020 compared to $96 million in the prior year. The primary driver is the recognition of $42 million from the U.S. government associated with reimbursements of REGEN-COV development. As we said on the third quarter call, this line item continues to trend lower due to the wind down of development reimbursements from the U.S. government. In 2021, we expect to record approximately half of the $557 million recorded in other revenue for full year 2020.

2020年第四季其他營收增至1.23億美元，去年同期為9,600萬美元。主要成長動力來自美國政府支付的4,200萬美元，這筆款項與REGEN-COV的研發費用報銷有關。正如我們在第三季財報電話會議上所述，由於美國政府研發費用報銷的逐步減少，該收入持續呈下降趨勢。我們預計2021年其他收入將約為2020年全年5.57億美元的一半。

Moving on to our operating expenses, and starting with R&D. R&D increased 50% year-over-year to $675 million, primarily due to continued clinical development costs for our REGEN-COV antibody cocktail and higher headcount to support our expanding pipeline. Next, SG&A expense increased 22% year-over-year to $381 million. The year-over-year increase was largely driven by increased headcount, launch preparations for Libtayo and continued investments for growth in EYLEA. Cost of goods sold increased 79% from the prior year from $93 million to $166 million due to sales of REGEN-COV and Praluent in the U.S. Cost of collaboration and contract manufacturing was $174 million compared to $113 million in the fourth quarter 2019, primarily due to increased sales of Dupixent.

接下來是營運費用，首先是研發費用。研發費用年增50%至6.75億美元，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員工人數。其次，銷售、管理及行政費用較去年同期成長22%至3.81億美元。年比成長的主要原因是員工人數增加、Libtayo的上市準備工作以及對EYLEA持續成長的投資。銷售成本較上年同期成長79%，從9,300萬美元增加至1.66億美元，主要原因是REGEN-COV和Praluent在美國的銷售額成長。合作及合約生產成本為1.74億美元，而2019年第四季為1.13億美元，主要原因是Dupixent的銷售額成長。

Additionally, in other operating income and expense, we recorded $145 million of income in the fourth quarter of 2020. This includes approximately $100 million of income related to higher recognition of upfront and milestone payments previously received from our collaborators with Sanofi, Teva and Mitsubishi Tanabe. Finally, in other income and expense, we recorded $2 million of expense compared to $25 million of income in the fourth quarter of 2019. This is driven by interest expense related to our $2 billion debt issuance in August 2020 and lower investment returns on our existing cash and marketable securities.

此外，在其他營業收入和支出方面，我們在2020年第四季錄得1.45億美元的收入。其中包括約1億美元的收入，這主要得益於先前從賽諾菲、梯瓦和三菱田邊製藥等合作夥伴處收到的預付款和里程碑付款確認金額的增加。最後，在其他收入和支出方面，我們錄得200萬美元的支出，而2019年第四季則錄得2,500萬美元的收入。這主要是由於2020年8月發行的20億美元債券所產生的利息支出，以及現有現金和有價證券的投資報酬率下降。

Turning now to taxes. The effective tax rate was 7.7% in the fourth quarter of 2020 compared to 10.6% in the fourth quarter of 2019.

現在來說說稅收。 2020年第四季的實際稅率為7.7%，而2019年第四季為10.6%。

Shifting now to cash flow and the balance sheet. For the full year 2020, Regeneron generated $2 billion in free cash flow and ended the year with cash and marketable securities, less long-term debt, of $4.7 billion. We also exhausted our inaugural $1 billion share repurchase program in the fourth quarter.

接下來我們來看現金流和資產負債表。 2020年全年，Regeneron公司創造了20億美元的自由現金流，年末現金及有價證券（扣除長期債務）總額為47億美元。此外，我們在第四季完成了首輪10億美元的股票回購計畫。

As a result of our strong balance sheet and confidence in the growth trajectory of our business, we are announcing a new Board-authorized share repurchase program of $1.5 billion. This program is consistent with our capital allocation priorities of funding our broad R&D pipeline, investing in enabling and synergizing R&D business development opportunities and returning cash to our shareholders. With this new authorization, we will continue to be opportunistic buyers where we see dislocation between our stock price and our intrinsic valuation.

鑑於我們穩健的資產負債表以及對業務成長前景的信心，我們宣布一項經董事會批准的15億美元股票回購計畫。該計劃符合我們的資本配置優先事項，即為廣泛的研發項目提供資金，投資於研發業務發展機會的賦能和協同效應，以及向股東返還現金。憑藉這項新的授權，我們將繼續在股價與其內在價值出現偏差時，伺機回購股票。

Having reviewed our fourth quarter performance, I'd like to take some time to discuss the 2021 financial outlook, starting with R&D guidance.

在回顧了我們第四季的業績之後，我想花點時間討論一下 2021 年的財務前景，首先從研發指導說起。

We forecast our 2021 R&D expense to be in the range of $2.7 billion to $2.85 billion. We are continuing to advance programs in our diverse R&D portfolio, with up to 7 INDs to enter the clinic in 2021, of which 6 were discovered in-house. This is in addition to INDs that entered the clinic in 2020 which George mentioned. Included in our R&D guidance and based on current plans, we expect to spend between $275 million and $350 million on the REGEN-COV development program. We expect most of this REGEN-COV spend to occur in the first half of the year.

我們預計2021年研發支出將在27億美元至28.5億美元之間。我們持續推動多元化研發項目組合中的各項計劃，預計2021年將有至多7項新藥臨床試驗申請（IND）進入臨床試驗階段，其中6項為公司自主研發。這還不包括喬治提到的2020年已進入臨床試驗階段的新藥臨床試驗申請。根據目前的計劃，並已納入我們的研發指導，我們預計將在REGEN-COV研發項目上投入2.75億美元至3.5億美元。我們預計大部分REGEN-COV研發支出將在今年上半年發生。

Next, we forecast our 2021 SG&A expense to be in the range of $1.5 billion to $1.63 billion. We continue to invest in multiple launches in 2021, including 2 new indications for Libtayo and efforts for REGEN-COV. Also, as you heard from Marion, this increased spending will also be driven by a DTC campaign for EYLEA as we continue to see significant growth opportunity in diabetic eye disease.

接下來，我們預計2021年的銷售、管理及行政費用（SG&A）將在15億美元至16.3億美元之間。我們將繼續投資2021年的多項產品上市，包括Libtayo的兩項新適應症以及REGEN-COV的研發工作。此外，正如Marion所說，由於我們持續看到糖尿病眼疾領域存在巨大的成長潛力，EYLEA的直接面向消費者（DTC）行銷活動也將推動支出增加。

Next, we expect our 2021 product gross margin on a percentage of net product sales that we record to be between 87% and 89%. We expect 2021 cost of collaboration manufacturing to be in the range of $670 million to $750 million driven by continued growth in our Dupixent franchise. We forecast 2021 operating income and expense to be income of $150 million to $175 million. Finally, we expect our 2021 non-GAAP tax rate to be in the range of 12% to 14%, inclusive of REGEN-COV sales in the U.S. which are taxed at the U.S. statutory rate.

接下來，我們預計2021年產品毛利率（以淨產品銷售額百分比計算）將介於87%至89%之間。我們預計2021年合作生產成本將在6.7億美元至7.5億美元之間，主要得益於Dupixent產品線的持續成長。我們預測2021年營業收入和支出分別為1.5億美元至1.75億美元。最後，我們預計2021年非GAAP稅率將在12%至14%之間，其中包括在美國按美國法定稅率徵稅的REGEN-COV銷售額。

I'd also like to review our current supply agreements with the U.S. government for REGEN-COV. We expect to recognize the remainder of the $466 million initial U.S. government contract in the first quarter of 2021. We also announced last month a new agreement with the U.S. government for additional doses of REGEN-COV. Right now, we expect to deliver approximately 750,000 doses by the agreed delivery date of June 30 this year at the contracted price of $2,100 per dose with the vast majority of these deliveries occurring in the second quarter.

我還想回顧一下我們目前與美國政府簽訂的REGEN-COV疫苗供應協議。我們預計在2021年第一季確認剩餘的4.66億美元美國政府初始合約款項。上個月，我們也宣布與美國政府達成新的協議，增購REGEN-COV疫苗。目前，我們預計將在今年6月30日約定的交付日期前交付約75萬劑疫苗，合約價格為每劑2,100美元，其中絕大部分將在第二季交付。

As George mentioned earlier, we are evaluating a lower 1.2-gram dose for REGEN-COV. Should this lower treatment dose receive emergency use authorization or approval of the FDA, we aim to deliver up to 1.25 million doses by June 30, which is the maximum quantity that is authorized for purchase by the U.S. government under the supply agreement. Importantly, if the lower dose is approved, the pricing per dose does not change. Our ability to fulfill these finished doses is predicated on continued success in the manufacture of bulk product and access to third-party fill/finish capacity, which is under heavy demand from COVID-19 vaccine manufacturers.

正如喬治之前提到的，我們正在評估 REGEN-COV 的較低劑量方案，即 1.2 克。如果該較低劑量方案獲得美國食品藥物管理局 (FDA) 的緊急使用授權或批准，我們的目標是在 6 月 30 日前交付最多 125 萬劑，這是根據供應協議美國政府獲準購買的最大數量。重要的是，即使較低劑量方案獲得批准，每劑的價格也不會改變。我們能否按時交付這些成品，取決於散裝產品生產的持續成功以及能否獲得第三方灌裝/包裝產能，而這些產能目前正受到新冠疫苗生產商的強烈需求。

In conclusion, we are well positioned for significant growth with durable core products, multiple near-term launches in specialized growth opportunities while investing in our R&D engine to drive sustainable long-term growth.

總而言之，我們擁有經久耐用的核心產品，近期將在多個專業成長領域推出新產品，同時加大研發投入，以推動可持續的長期成長，因此我們已做好充分準備實現顯著成長。

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. Michelle, that concludes our prepared remarks. We'd now like to open the call for Q&A. We have more than 20 callers in the queue today. (Operator Instructions)

謝謝鮑勃。米歇爾，我們的演講到此結束。現在開始問答環節。今天有超過20位聽眾在排隊等候。 （操作員提示）

Please go ahead, Michelle.

請繼續，米歇爾。

(Operator Instructions) Our first question comes from Chris Raymond with Piper Sandler.

（操作說明）我們的第一個問題來自 Piper Sandler 公司的 Chris Raymond。

So I heard the -- this question is on REGEN-COV. So I heard Marion's prepared remarks around working to iron out some of the reported logistical and arguably financial barriers that have been talked about so much in the real-world setting. But I'm guessing, with the development path being as compressed as it was, your commercial support is probably playing catch up a bit here. But can you maybe talk a little bit about, more specifically, what you guys feel needs to be worked on the most? Is it education of physicians? Is it the logistical issues, what kind of support? Any color there in terms of what exactly you need to do to sort of smooth things out would be great.

我聽到了——這個問題是關於 REGEN-COV 的。我聽到了 Marion 事先準備好的發言，她談到瞭如何努力解決一些在實際應用中經常被提及的後勤和財務方面的障礙。但我猜想，由於研發路徑如此緊湊，你們的商業支持可能有點跟不上進度。你們能否更具體地談談，你們認為最需要改進的地方是什麼？是醫生培訓嗎？是後勤問題嗎？需要什麼樣的支持？如果能具體說明一下你們需要做些什麼來理清這些方面，那就太好了。

Sure. It's Len. Marion can give you more details. But the way we look at it, we need to do work at all parts of the funnel. The top end of the funnel being getting physicians to actually prescribe the product for the appropriate patients; and as well as at the bottom end of the funnel, which is -- gets quite narrow in some places, allowing people to easily get administered the product once the physician wants to treat the patient.

當然。我是Len。 Marion可以提供更多細節。但我們認為，我們需要在銷售漏斗的各個環節都開展工作。漏斗的頂端是讓醫生為合適的患者開立處方；漏斗的底端——在某些環節會比較狹窄——也需要確保患者在醫生決定治療後能夠方便地獲得該產品。

There's been a lot of progress on both ends there. On the bottom end of the funnel, there have been best practices emerging, where people have linked directly medical record algorithms to positive patients, asking their doctor if they want to get a consult to administer the cocktail, and they've administered lots and lots of doses of monoclonal antibodies. And there -- these best practices are emerging around the country.

兩端都取得了很大進展。在治療漏斗的末端，已經湧現出一些最佳實踐，例如將醫療記錄演算法直接與陽性患者關聯起來，詢問他們的醫生是否需要會診以進行聯合治療，並且已經註射了大量的單株抗體。這些最佳實踐正在全國各地推廣。

On the top end, there is still some skepticism that the data is incomplete, that the data isn't robust enough. And we certainly would agree we don't have the normal data standards that you might have for a full FDA approval, but we remind everybody that we are in the midst of a pandemic where thousands, hundreds of thousands of people are going to die and have died. And sometimes, one has to look at the totality of the evidence and make decisions in that regard.

在高端市場，仍存在一些質疑，認為數據不完整，數據不夠可靠。我們當然承認，我們目前的數據標準可能達不到FDA全面批准的標準，但我們想提醒大家，我們正處於一場全球大流行之中，成千上萬的人將會、甚至已經死亡。有時，我們必須全面審視所有證據，並據此做出決定。

So we continue on the top end education and the logistics on the bottom end. Marion might want to add something.

所以我們繼續專注於高端教育和低端物流。瑪莉昂或許想補充一些內容。

Thanks, Len. And Chris, I would just add that, as Len points out, we continue to work with all of our stakeholders to improve in all dimensions, top level. And at the local level, it's not a traditional commercialization. Under the emergency use authorization, we're working very closely with the government in helping stakeholders with education. The efforts of our medical affairs team in the marketplace has been paramount, our trade and market access group, our policy and government teams. So we have a lot of work to do, but we are making progress, and I do think that's very, very encouraging.

謝謝Len。 Chris，我還要補充一點，正如Len所指出的，我們一直在與所有利害關係人合作，力求在各個層面，包括最高層面，都取得進步。在地方層面，這並非傳統的商業化模式。在緊急使用授權下，我們正與政府密切合作，幫助利害關係人進行教育。我們的醫療事務團隊、貿易和市場准入團隊以及政策和政府團隊在市場推廣方面都做出了至關重要的努力。因此，我們還有很多工作要做，但我們正在取得進展，我認為這非常令人鼓舞。

Most encouraging is all -- of all is when we talk to the physicians and KOLs that have used REGEN-COV, they report positive results. And some -- at this point, some facilities have used antibodies and our antibody cocktail to treat hundreds and thousands of patients. So the best practices are growing, and we're going to appropriately accelerate that learning.

最令人鼓舞的是，當我們與使用 REGEN-COV 的醫生和關鍵意見領袖交流時，他們都報告了積極的治療效果。目前，一些醫療機構已經使用抗體和我們的抗體雞尾酒療法治療了數百名患者。因此，最佳實踐正在不斷發展，我們將適當地加快這一學習進程。

Our next question comes from Cory Kasimov with JPMorgan.

下一個問題來自摩根大通的科里·卡西莫夫。

On Dupixent, given the time on market and the broad favorable feedback everyone seems to get on the product, why do you believe it's only penetrated roughly 6% in the U.S. in -- for atopic derm? And what do you think is the key here over the next year or 2 to unlocking a lot more?

鑑於Dupixent上市已有一段時間，而且似乎每個人都對該產品給予了廣泛的好評，您認為為什麼它在美國治療異位性皮膚炎的市場滲透率只有大約6%？您認為在未來一兩年內，突破這一瓶頸的關鍵是什麼？

Sure. Let me take a start, Cory, on that. I think that for patients with atopic dermatitis, there had been so little for so long that over the course of several years now where Dupixent has been in the marketplace, the amazing efficacy, the safety profile, the convenience of use is something that has required a lot of market education and a lot of market understanding. And across the approved indications that we have in the U.S. today, there are about 2 million, 2.2 million actually eligible patients and only about 6% are getting treatment today.

當然。科里，讓我先來談談這個問題。我認為，對於異位性皮膚炎患者來說，長期以來治療選擇非常有限。而杜必利松（Dupixent）上市幾年後，其卓越的療效、安全性以及使用便利性，都需要大量的市場教育和深入的市場了解。目前，杜必利鬆在美國核准的適應症範圍內，約有200萬到220萬符合治療條件的患者，但只有約6%的患者正在接受治療。

So while favorable results in the understanding of Dupixent with dermatologists, allergists, all of our prescribers; and obviously in asthma now with pulmonologists and allergists; for nasal polyps with the ENTs as well, this is a remarkable alternative across type 2 disease for approved indications today. But there's a lot of unmet need. And obviously, the future indications will take us into new populations and new prescribers.

因此，儘管皮膚科醫生、過敏科醫生以及所有處方醫生對Dupixent的理解都取得了令人滿意的成果；肺科醫生和過敏科醫生也開始認可其在哮喘治療方面的應用；耳鼻喉科醫生也開始認可其在鼻息肉治療方面的應用，但就目前已獲批准的適應症而言，Dupixent在2型哮喘疾病領域仍是一種卓越的替代療法。然而，仍存在許多未被滿足的醫療需求。顯然，未來的適應症擴展將使我們惠及更多人群和新的處方醫生。

I also think there's a lot of education that needs to be done because, obviously, there's a long legacy in which people believe that drugs that you might take by mouth, things like JAK inhibitors or things like steroids, are not as serious drugs as drugs that you take by an injection or biologicals. And I think that most people -- or most sophisticated people are beginning to realize now that it's the biologicals, particularly a drug like Dupixent, which is more targeted, more natural and less prone to an assortment of both on-target and off-target toxicities.

我也認為需要進行大量的教育工作，因為很顯然，長期以來人們一直認為口服藥物，例如JAK抑制劑或類固醇，不如注射藥物或生物製劑那麼嚴重。我認為現在大多數人——或者說大多數有見識的人——都開始意識到，生物製劑，特別是像Dupixent這樣的藥物，靶向性更強，更天然，而且更不容易產生各種靶向和非靶向毒性。

And so people think, oh, a pill, it's less serious, and I think we have to do a lot of education to explain that these biologicals are actually more targeted, more natural, they can be a lot safer. And though they're more powerful, you don't have to think of them as more serious in a negative way. So I think there's a huge legacy of thinking of things like that, but the emerging data that's coming out now is going to help, I think, with these points. That if you're suffering from a disease like atopic dermatitis, you want to be on a natural approach, targeted biological, something that has an exquisite safety profile like Dupixent.

所以人們會想，哦，吃藥而已，沒那麼嚴重。我認為我們必須做很多教育工作來解釋，這些生物製劑實際上更具靶向性、更天然，也更安全。雖然它們藥效更強，但你不必因此就認為它們更危險。我認為這種想法由來已久，但現在湧現的新數據將有助於澄清這些問題。如果你患有像異位性皮膚炎這樣的疾病，你應該選擇更天然的治療方法，使用標靶生物製劑，例如像Dupixent這樣安全性極高的藥物。

Our next question comes from Terence Flynn with Goldman Sachs.

下一個問題來自高盛的 Terence Flynn。

Great. Thanks again for all the work on the COVID front. I really appreciate all the effort. I know you guys have been working hard there.

太好了。再次感謝你們在新冠疫情防治上所做的一切努力。我非常感激你們的付出。我知道你們一直都很辛苦。

Just a question for George. You mentioned the efficacy signals you're seeing with your MUC16 bispecific in ovarian cancer. Just wondering if you can elaborate a little bit more there. Is that a RECIST response? Is it CA125 or maybe another biomarker? And then where -- on the safety front, any initial -- anything initially you can share there as well?

喬治，我有個問題。你曾提到你用MUC16雙特異性抗體治療卵巢癌觀察到的療效訊號。我想請你詳細說說。這是RECIST療效反應嗎？是CA125指標，還是其他生物標記？另外，在安全性方面，有什麼初步結果可以分享嗎？

Right. Well, I can tell you, when I say efficacy, it relates to both RECIST and CA125 measures. I don't think that we have given any specifics on that, and we're waiting for an appropriate medical venue in which to present the data. But we are pretty excited about the preliminary evidence of activity. And as I said, we'll be giving all the details at an upcoming scientific meeting.

好的。我可以告訴您，我所說的療效是指RECIST和CA125指標。我們目前還沒有公佈具體細節，正在等待合適的醫學會議來發布數據。但我們對初步的療效證據感到非常興奮。正如我所說，我們將在即將舉行的科學會議上公佈所有細節。

Our next question comes from Geoffrey Porges with SVB Leerink.

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

And George, a couple of questions on the allergy or related. You sound quite excited about the allergy programs now. And just wondering if you could tell us a little bit about the path forward for peanut allergy and whether you think this will ultimately be a maintenance treatment for a significant population.

喬治，關於過敏或相關問題，我有幾個問題。聽起來你對目前的過敏症治療計畫非常感興趣。我想請你談談花生過敏症的未來發展方向，以及你認為花生過敏症最終是否會成為相當一部分人群的長期治療方案。

Yes. I think that we're very excited about our entire allergy portfolio because we really think we have a collection of powerful but also groundbreaking new approaches. So as we all know, so many people, millions in the United States, are taking, for example, multiple shots weekly to try to get desensitized; or undergo these very long prolonged oral approaches and so forth, often with unsatisfying results, even after years of therapy. So I think it's exciting as we announced that we were able to demonstrate a significant improvement in the amount of peanut tolerization that could occur in conjunction with the Aimmune oral immunization -- oral desensitization approach.

是的。我認為我們對整個過敏產品組合感到非常興奮，因為我們相信我們擁有一系列強效且突破性的創新療法。眾所周知，許多人，例如在美國，每週都要注射多針來嘗試脫敏；或者接受漫長的口服療法等等，但即使經過多年的治療，效果往往也不盡如人意。因此，我們宣布能夠證明，結合Aimmune口服免疫療法（即口服脫敏療法），花生耐受性的顯著提高，這令人振奮。

And we think that this is going to prove to be generalizable across the board to many of these desensitization approaches, where we hope that Dupixent will aid in making patients more desensitized, may be able to tolerate these regimens better as well as maybe improve more quickly. And that's one component of our allergy program.

我們認為，這種方法可以推廣到許多減敏療法中，我們希望Dupixent能夠幫助患者更好地減敏，提高他們對這些療法的耐受性，並可能加快病情好轉。這是我們過敏治療方案的一部分。

We're equally excited about a somewhat unrelated effort where we're the first people who are moving into the clinic antibodies that directly bind and neutralize allergens. I for one don't understand why this hasn't been done before. But our data, some of which we have talked about publicly and even published, and some of which we will be presenting at upcoming meetings, show that these are very powerful approaches. From the first injection, almost immediately at the first time measures, we're getting the sorts of improvements that you see across studies resulting after years of desensitization therapy.

我們對另一項看似無關的研究也同樣感到興奮，我們是第一批將能直接結合併中和過敏原的抗體推進臨床試驗的團隊。我個人不明白為什麼之前沒有人這樣做。但我們的數據（其中一些我們已經公開討論甚至發表，另一些我們將在即將舉行的會議上展示）表明，這些方法非常有效。從第一次注射開始，幾乎在第一次測量時，我們就獲得了與多年脫敏治療後才能觀察到的療效相當的改善。

And we're talking about 2 of the most important allergies, which are both associated with asthma, in which settings because of safety concerns, desensitization approaches are not indicated. That is cat allergy and birch allergy. The results are really striking. We think this is an entirely new way to fight allergy, one in which you can almost see the benefit immediately. Once again, it's a very natural and biologic and targeted approach.

我們正在討論兩種最重要的過敏症，它們都與氣喘有關，出於安全考慮，脫敏療法並不適用於這些情況。這兩種過敏症分別是貓過敏和樺樹過敏。結果非常顯著。我們認為這是一種全新的抗過敏方法，幾乎可以立即見效。再次強調，這是一種非常天然、生物活性且有針對性的方法。

There are millions of people who are affected by these. And I think knowing many of them having -- many of them in my family, I can tell you that they would -- if we really continue to show the sort of safety and efficacy that the initial studies are showing, I think a lot of people would welcome the opportunity to take the shot and have immediate benefit in terms of their serious allergies. And it's an entirely new approach.

數以百萬計的人受這些疾病的影響。我認識很多這樣的人——我的家人中就有不少——我可以告訴你，如果我們真的能繼續展現出初步研究顯示的安全性和有效性，我相信很多人都會樂於接受這種注射，並立即從嚴重的過敏症狀中獲益。這是一種全新的治療方法。

And all of these things are synergistic, of course. We can imagine many ways in which we can be combining and mixing and matching various parts of our portfolio, including things like Dupixent in these anti-allergens, but with other approaches as well.

當然，所有這些都是協同作用的。我們可以設想多種方式，將我們產品組合中的各種產品進行組合、混合和搭配，包括像Dupixent這樣的抗過敏藥物，以及其他方法。

So we really think that we may be at the door of a whole new era, a biologics approach to treating allergy, which I think can really change everything for so many people. And we know that, according to the CDC, allergic diseases are now approaching and increasing in epidemic proportion. So there's a real need out there, and there's a real need for totally new approaches. And so we're very excited about them.

所以我們真的認為，我們可能正站在一個全新時代的門口，一個以生物製劑治療過敏症的新時代，我認為這將徹底改變許多人的生活。我們知道，根據美國疾病管制與預防中心（CDC）的數據，過敏性疾病正以驚人的速度蔓延，甚至接近流行程度。因此，人們迫切需要全新的治療方法。對此，我們感到非常興奮。

Our next question comes from Ronny Gal with Bernstein.

下一個問題來自伯恩斯坦公司的羅尼·加爾。

Question are on the plans for non-small cell lung cancer. With you guys being so close to the launch, I was wondering if you can show us a little bit more about your launch plans. It seems that you'll have to use some sort of a targeting approach and segmentation to see where you'll be able to penetrate the market given you're coming in late. Can you share a little bit about more -- a little bit more about it? And kind of like what range of upside do we expect from this market? What would you be happy with?

關於非小細胞肺癌的計劃，我們有一些疑問。鑑於你們即將推出新產品，我想請你們詳細介紹一下上市計劃。考慮到你們進入市場較晚，似乎需要採取某種目標市場定位和細分策略，才能找到合適的市場切入點。能否再詳細分享一下？例如，你們對這個市場的成長潛力有何預期？你們對達到什麼目標感到滿意？

Yes, Ronny, and it's Len. I want to just make one comment about that were coming in late and then say that we probably won't answer on launch plans. We have to get our final label, and we certainly don't want to tip off any of our competitors of what we're up to. But we're spending a lot of time, obviously, thinking about that.

是的，羅尼，我是倫。我只想補充一點，我們來晚了，而且我們可能不會透露發布計劃。我們得先敲定最終的標籤，當然，我們不想讓任何競爭對手知道我們的動向。但很顯然，我們正在花很多時間考慮這個問題。

But let me just address one comment you made, which was that you said coming in late. I remember, and it may have been you, but it probably was somebody else who asked us the question, why were we even bothering with Libtayo in non-small cell lung cancer? Because by the time you get it approved, there will be 10 others that are there. And I remember George answering that question saying, well, he's not so sure that there will be 10 others. All antibodies aren't created equal, plus, it would be a foundation for the rest of our business.

但我想就您剛才提到的一點發表一下看法，那就是您說我們入局較晚。我記得，也許是您問的，也可能是其他人問的，我們為什麼要費勁研發Libtayo用於非小細胞肺癌？因為等到它獲準的時候，可能已經有十幾種同類藥物上市了。我記得喬治當時回答說，他不太確定是否真的會有十幾種同類藥物。並非所有抗體藥物都一樣，而且，Libtayo的核准將為我們未來的業務奠定基礎。

And that wisdom has really panned out because if you look almost every day, there's another failure of a PD-L1 or inferior PD-1, it doesn't combine right, all sorts of things. And there really is only one right now, one gold standard, which is KEYTRUDA. And obviously, we don't have any head-to-head data. But when you look at our data, it's really impressive data. And so we think that we should remind everybody that the questions that we got 5 or 10 years ago, why bother, have sort of panned out more the way George had anticipated rather than maybe everybody else had.

事實證明，這種智慧確實得到了驗證，因為幾乎每天都有新的PD-L1抑製劑或療效較差的PD-1抑製劑上市，它們要么療效不佳，要么與其他藥物組合使用不理想，等等。目前真正有效的藥物只有一個，那就是KEYTRUDA，一個黃金標準。顯然，我們還沒有直接比較的數據。但當你查看我們的數據時，你會發現它非常出色。因此，我們認為應該提醒大家，5到10年前我們被問到的「為什麼要費這個勁」的問題，如今看來，結果比喬治·盧卡斯（George Lukas）的預期更加接近現實，而不是像其他人那樣。

As far as our specific launch plans, we'll ask you to stay tuned because we're working hard at preparing.

至於具體的發布計劃，請大家繼續關注，因為我們正在努力準備。

Our next question comes from Kennen MacKay with RBC Capital Markets.

下一個問題來自加拿大皇家銀行資本市場的 Kennen MacKay。

What a year, indeed. Maybe a question on EYLEA. A couple of years ago, you got it completely right on some of the emerging competition not being as big of risk, as myself and some of The Street had anticipated would be. But just would love to get your perspective on some of the new data from the Ang-2, and kind of how you're thinking about some of the evolving competition there again, given you were certainly right in the past.

真是跌宕起伏的一年。或許我想問一個關於EYLEA的問題。幾年前，您對一些新興競爭對手的風險並沒有我和華爾街一些人士預期的那麼大，您的預測完全正確。我很想聽聽您對Ang-2新數據的看法，以及您如何看待這些不斷變化的競爭對手，畢竟您過去的預測確實很準確。

Sure. I think George touched on it, but let me deal specifically as best we can for the product you referenced from Roche, which is a combination of anti-VEGF and anti-Ang-2. I might start out by saying we have the greatest respect for Roche-Genentech, the group. We partner with them in our COVID global efforts and we watched them really establish the anti-VEGF class with Lucentis. So we have tremendous respect for them.

當然。我想喬治已經提到了，但我想就您提到的羅氏產品——一種抗VEGF和抗Ang-2的複方製劑——具體談談我的看法。首先，我想說我們對羅氏-基因泰克集團非常尊敬。我們與他們合作進行全球對抗新冠疫情的工作，並且親眼見證了他們憑藉Lucentis成功開創了抗VEGF藥物領域。因此，我們對他們充滿敬意。

But I think when it comes to Ang-2, history has a very important lesson here, in that I was with George, I remember it, we were [tracking]. I was with George, when one of his colleagues, they were working so hard to identify, purify and clone and sequence this really important molecule that was seen to be a critical player in blood vessel formation and development, et cetera, and maybe the only real other critical factor other than VEGF. So George and his group discovered this molecule, and nobody would like to see it bear fruit in terms of a treatment? But the data that we have just don't support that. Our data, we look very carefully, we could not find a benefit of adding Ang-2 to the amazing effect get with a highly potent anti-VEGF compound such as EYLEA.

但我認為，就Ang-2而言，歷史為我們提供了一個非常重要的教訓。我記得當時我和喬治在一起，我們一直在追蹤Ang-2的來源。當時，他的一位同事正努力鑑定、純化、克隆和定序一種非常重要的分子，這種分子被認為是血管形成和發育的關鍵因素，或許是VEGF以外唯一真正重要的因子。喬治和他的團隊發現了這種分子，難道沒有人希望它能用於治療嗎？但我們掌握的數據並不支持這一點。我們仔細分析了數據，發現添加Ang-2並不能增強像EYLEA這樣高效抗VEGF化合物的療效。

So when we look at the data you refer to, it's -- we haven't seen all the data, and we'll all look for it. But from what they've disclosed, somewhere in the 40s percent, to be able to get to a 16-week regimen is what George referred to is exactly what EYLEA gets in the ALTAIR study. So we don't see so far any evidence, we'll look at the data, that there's anything more there than high dose anti-VEGF therapy, higher than Lucentis on a molar basis. And so we'll have to wait and see.

所以，當我們查看您提到的數據時，我們還沒有看到全部數據，我們都會繼續尋找。但根據他們已揭露的訊息，大約有40%的患者能夠達到16週的療程，這正是喬治提到的，也是艾力達在ALTAIR研究中接受的治療方案。因此，到目前為止，我們還沒有看到任何證據表明，除了高劑量抗VEGF療法（按摩爾濃度計算高於雷珠單抗）之外，還有其他更有效的療法。所以我們只能拭目以待。

But one has to remember also that safety, George mentioned, we have 30 million injections under our belt. That's a tremendous, tremendous safety database. And you can see what happens. There's been a reminder out there just how important the safety side of this is.

但喬治也提到，我們必須記住安全問題。我們已經累積了3000萬次注射的經驗。這是一個非常龐大的安全資料庫。你可以看到結果。我們已經多次提醒大家，安全方面有多重要。

So we'll see. We have great respect for them. But we don't see any data right now to suggest Ang-2 blockade is playing any differentiated role, if any role at all.

所以我們拭目以待。我們非常尊重他們。但目前我們沒有任何數據顯示Ang-2封鎖發揮了任何特殊作用，或者根本不起作用。

I don't know, George, if the discover or Ang-2, do you want to comment further?

喬治，我不知道，關於發現號還是Ang-2，你還有什麼想補充的嗎？

Just very quickly. As Len said, we discovered the entire family of the angiopoetins. And we obviously made the first, and we think the best, antibodies against these factors. We tried them in combination studies. I think that there is no evidence at all from any of the faricimab data that there's any additional benefit vis-à-vis mechanism of action of the combined blockade of the angiopoietin-2.

簡單來說，正如Len所說，我們發現了整個血管生成素家族。而且，我們顯然研發了第一個，也是我們認為最好的針對這些因子的抗體。我們嘗試了聯合用藥研究。我認為，從法瑞西單抗的任何數據來看，都沒有證據表明，聯合阻斷血管生成素-2在作用機制上有任何額外的益處。

I think that it's sort of a regulatory trick to try to create a differentiated molecule, put both activities within one. We think it's a better, more convincing, frankly, safer approach to actually test both blocking agents separately rather than combining them in 1 molecule when there's no benefit other than pure regulatory tricks for combining them into 1 molecule.

我認為這是一種監管上的伎倆，試圖創造出一種具有差異化功能的分子，將兩種活性成分融合在一個分子中。我們認為，與其將它們組合成一個分子，不如分別測試這兩種阻斷劑，這樣更好、更有說服力，也更安全。因為除了純粹的監管伎倆之外，將它們組合成一個分子並沒有任何其他好處。

The way we think that the data looks right now, it looks as if this is merely high dose Lucentis, and the data that they've at least reported to date suggests similar data to what we see right now currently with EYLEA. As Len mentioned, we have studies that show that up to 40% of patients can achieve 16-week dosing. I think the important add on to it is, of course, is that we have our upcoming studies with high-dose EYLEA.

根據我們目前掌握的數據來看，這似乎只是高劑量雷珠單抗（Lucentis）的療效，而且他們迄今為止公佈的數據至少與我們目前觀察到的EYLEA療效相似。正如Len所提到的，我們的研究表明，高達40%的患者可以完成16週的給藥療程。當然，我認為更重要的是，我們即將進行高劑量EYLEA的研究。

So basically, what people are doing, they're taking other molecules which didn't fare as well, and they're high-dosing them, okay? We're taking EYLEA and we're a high dosing it. And it's already starting at a place where its duration and its efficacy and its safety seem to be leading, with really no evidence that the competition has anything significantly different. But now we're testing the higher dose to see whether we can make EYLEA even better while still delivering the same safety and efficacy.

所以基本上，人們現在的做法是，他們服用其他效果不佳的分子，然後加大劑量，懂嗎？我們服用的是EYLEA，我們也在加大劑量。 EYLEA的持續時間、療效和安全性似乎都處於領先地位，而且沒有證據表明競爭對手的產品有任何顯著差異。但現在我們正在測試更高劑量，看看能否在保持相同安全性和療效的前提下，進一步提升EYLEA的效果。

So we're pretty excited about that. And as we said, we see there's no evidence that any of the competitors are providing anything different at this point.

所以我們對此感到非常興奮。正如我們所說，目前沒有任何證據表明任何競爭對手提供的產品或服務與我們的產品或服務不同。

Our next question comes from Evan Seigerman with Crédit Suisse.

我們的下一個問題來自瑞士信貸的埃文·塞格曼。

Thanks for all the work on the COVID-19 antibody. So I'm looking at REGN1979. Assuming that the trial resumes near term, what do you really need to demonstrate in this Phase II potentially pivotal trial for submission next year? I believe you kind of highlighted that earlier in the year.

感謝您在新冠病毒抗體研發上所做的一切。我現在正在關注REGN1979。假設試驗近期能夠恢復，為了明年提交申請，您在這項可能具有關鍵意義的II期試驗中究竟需要證明哪些內容？我相信您在今年早些時候已經重點強調過這一點。

Yes. I think that basically, what we have to do is just continue to see the efficacy and build on the duration that we've seen, while continuing to also decrease on any of the safety concerns and so forth. But I think the data, as it stands right now, would be very supportive of an approval as long as we can confirm it in larger numbers, and importantly, build on the already very impressive duration with some responses exceeding the year time frames.

是的。我認為，基本上，我們必須繼續觀察療效，並鞏固已觀察到的持續時間，同時繼續減少任何安全隱患等等。但我認為，就目前的數據而言，只要我們能在更大樣本量中證實其療效，並且更重要的是，在已經非常顯著的持續時間基礎上繼續延長（部分患者的療效持續時間超過一年），那麼這些數據將非常有利於批准該藥物上市。

So we're very excited about it. Obviously, there's always concerns and hurdles we have to get over. But assuming that we can get past them and we can resume enrollment and continue with the study, we hope that the data, as it matures and accrues, will continue to support that it's an important option that these patients can have.

所以我們對此感到非常興奮。當然，總是會有一些擔憂和障礙需要克服。但假設我們能夠克服這些困難，恢復招募並繼續進行研究，我們希望隨著數據的不斷改進和積累，能夠持續證明這對這些患者來說是一個重要的治療選擇。

Next question comes from Yaron Werber with Cowen.

下一個問題來自 Cowen 公司的 Yaron Werber。

George, maybe just for you. We're all very excited about the costim strategy. We'll get data at some point either late this year or next year. But how do you -- when you're thinking about costim with a CD28 and also hitting the CD3 axis with a bispecific, how would that work? If you could just give us a preview.

喬治，也許這個問題只問你。我們都對共刺激策略感到非常興奮。我們會在今年稍後或明年某個時候獲得數據。但是，當你考慮用CD28進行共刺激，同時用雙特異性抗體標靶CD3軸時，你會怎麼做？可以給我們簡單介紹一下嗎？

And then just for Bob, for you, just the REGEN-COV...

然後，就為了鮑勃，為了你，就為了再生冠狀病毒…

One question, Yaron. Sorry.

亞倫，我有個問題。不好意思。

Well, Len cut you off there.

嗯，Len打斷你了。

But just in terms of the costims. So as we've shown in some very high profile papers in Science and Science Translational. Basically, nature uses -- to activate T cells to do their job, particularly, for example, to kill cells, they need signal 1 through the T cell receptor itself, which is, a CD3 is an important component of that. But they also need signal 2, which some people refer to as a costimulatory signal. And so by combining bispecifics that involve CD3 engagement and bispecifics that involve CD28 or costimulatory engagement, you are simultaneously activating both signal 1 and signal 2. And we have shown rather compellingly in preclinical models that this really accentuates and really dramatically increases the ability of T cells to kill the target itself.

但就共刺激訊號而言，正如我們在《科學》和《轉化科學》等一些備受矚目的論文中所展示的那樣，自然界激活T細胞執行其功能（例如殺傷細胞）時，首先需要透過T細胞受體本身接收訊號1，其中CD3是重要的組成部分。但它們也需要訊號2，也就是有些人所說的共刺激訊號。因此，將涉及CD3結合的雙特異性抗體與涉及CD28或共刺激結合的雙特異性抗體結合使用，就可以同時活化訊號1和訊號2。我們在臨床前模型中已經相當有力地證明，這確實能顯著增強T細胞殺傷目標細胞的能力。

Let me we also remind you that the PD-1 and other checkpoint inhibitors provide a brake. So you have signal 1 and signal 2 which are driving the cells to kill, and then you can have a brake signal that acts through checkpoints such as PD-1. So combining all 3 or combining them in pair-wise fashion, in animal models, shows that you can just increase the amount of tumor killing that you get us compared with having just one of the approaches.

我們也要提醒各位，PD-1 和其他免疫檢查點抑制劑起到了「煞車」的作用。訊號 1 和訊號 2 會驅動細胞殺傷自身，而 PD-1 等免疫檢查點則扮演「煞車」的角色。因此，在動物模型中，將這三種方法結合起來，或兩兩結合使用，可以顯著提高腫瘤殺傷率，優於單獨使用其中任何一種方法。

So we're just trying to understand what nature does and how nature optimizes the process and then mimic it with these natural approaches to biologics that can activate in a targeted fashion only on the tumor target cells, depending on how well the targeting is, signal 1, signal 2, while releasing the brake. So the preclinical data is pretty compelling, and we can only hope that we approach it with what we're going to see in the clinic. And we do think that, over the next year, it's going to be very interesting to see how these dose escalation trials play out.

所以，我們只是想了解自然界是如何運作的，以及自然界如何優化這一過程，然後用這些天然的生物製劑方法來模擬自然，使其能夠靶向激活腫瘤靶細胞，具體激活方式取決於靶向效果，信號1、信號2，同時解除抑制。臨床前數據相當令人信服，我們只能希望它能與臨床試驗的結果相符。我們認為，在接下來的一年裡，觀察這些劑量遞增試驗的結果將會非常有趣。

We're a little bit past time. We still have 12 callers in the queue. We're going to try to get to 2 more, and then we'll catch up with everyone else following the call.

時間稍微晚了一點。還有12通電話在排隊。我們先接聽另外兩個，通話結束後再處理其他人的來電。

Our next question comes from Matthew Luchini with BMO Capital.

下一個問題來自 BMO Capital 的 Matthew Luchini。

I wanted to quickly come back to EYLEA competitive dynamics. And just trying to understand a little bit what your internal kind of market research is indicating about physician willingness to even really consider new drugs. In other words, what -- maybe you can share a little bit of a perspective on what impact the brolucizumab experience last year has had on their willingness to step away from a proven agent like EYLEA.

我想快速回到EYLEA的競爭格局上來。我只是想了解你們內部的市場調查結果，看看醫生們對新藥的接受度如何。換句話說，您能否分享一下去年brolucizumab的案例對他們放棄像EYLEA這樣已證實有效的藥物的意願產生了哪些影響？

Marion, you want to take that?

瑪莉昂，你想拿那個嗎？

Sure. I'm happy to take it. Well, I'll start with where you ended. I do think that the experience of the Novartis launch reset the table on the importance of safety and frankly, never assuming safety or assuming efficacy for any category, let alone when you're injecting into someone's eye and seeking to save their vision.

當然，我很樂意接受。好吧，我就從你剛才說的開始吧。我的確認為諾華的上市經驗重新定義了安全性的重要性，坦白說，任何藥物都不能想當然地認為安全或有效，更何況是往人眼裡注射，試圖挽救他們的視力。

We look at the competitive dynamic, as you know, very, very thoroughly. And I do think that EYLEA, during this period of time, the last couple of years but certainly during the pandemic, the characteristics of, breadth of indications, experience, the ability to treat and extend, now in a prefilled syringe for efficiency and throughput in the offices and this remarkable safety and efficacy profile make it an incredibly compelling choice for retinal specialists and injectors.

如您所知，我們對競爭格局進行了非常深入的分析。我認為，在過去幾年，尤其是在疫情期間，EYLEA憑藉其廣泛的適應症、豐富的經驗、治療和延長治療時間的能力，以及預充式註射器帶來的診室效率和操作速度，再加上其卓越的安全性和有效性，使其成為視網膜專科醫生和注射醫生的極具吸引力的選擇。

We -- obviously, even within our own portfolio, look to improvements like the EYLEA high dose for the future, the ability to treat and extend even further. But obviously, we've very deliberately, with our scientific teams, set a very, very high bar for competition.

顯然，即使在我們自己的產品組合中，我們也著眼於未來的改進，例如 EYLEA 高劑量療法，它能夠提供更全面的治療，並延長治療時間。但很顯然，我們的科學研究團隊已經非常明確地設定了非常高的競爭標準。

Yes. I think that vision is so important. We all know it, we all treasure it. Okay? And I think that there's a -- hopefully, hopefully, a new -- a realization once again about how important it is and how a catastrophic event that causes permanent loss of vision can be so catastrophic and so damning. And I think that when you have such a safe and effective agent with such an experience, one really has to take into consideration the risks, the potential catastrophic risk, of trying new approaches, unknown safety risks with their potential catastrophic risk.

是的。我認為視力非常重要。我們都知道這一點，我們都非常珍惜它。好嗎？而且我認為，人們——希望是新的——再次意識到視力有多重要，以及導致永久性失明的災難性事件會造成多麼巨大的破壞和毀滅性的後果。我認為，當有一種安全有效且經驗豐富的藥物時，人們確實必須考慮到嘗試新方法的風險，以及可能的災難性風險，包括未知的安全風險及其潛在的災難性後果。

All right. we have time for one more quick question.

好的，我們還有時間再問一個問題。

Our next question comes from Mohit Bansal with Citigroup.

下一個問題來自花旗集團的莫希特·班薩爾。

Congrats on the progress. In our conversations with experts, people -- doctors did talk about the potential use of Dupixent in milder patients, given its safety. So to that end, do you need to do a clinical trial to get there? Or do you think it is already happening to some extent at [doctor's] offices?

恭喜取得進展。當我們與專家交流時，醫生確實談到了Dupixent在病情較輕的患者中的潛在應用，因為它的安全性很高。那麼，是否需要進行臨床試驗才能實現這一目標？或者您認為目前在醫生診所中已經在一定程度上實現了？

The profile today for Dupixent treatment is for patients with moderate to severe disease, both in atopic dermatitis and also for patients that require biologic asthma treatment. I'll let team members talk about additional clinical work to that component, but that is our focus of the population. And as we discussed earlier, in the U.S. alone, we probably have about 2.2 million eligible patients just on the indications where we have approval today.

目前，Dupixent 的主要適應症是中重度異位性皮膚炎患者以及需要生物製劑治療的氣喘患者。關於這方面的其他臨床研究，我會讓團隊成員來詳細介紹，但這正是我們關注的重點族群。正如我們之前討論的，僅在美國，根據我們目前已獲批准的適應症，就有大約 220 萬符合條件的患者。

But to your comment, what I hear about time and time again from our physician prescribers and key opinion leaders is the remarkable safety profile based on a very specific mechanism of action, and that confidence in being able to treat not only adults, but now the younger age groups where we have indications, for example, in atopic dermatitis, not only for adolescents, but pediatric patients down to 6 years of age.

但對於您的評論，我從我們的醫生處方者和關鍵意見領袖那裡一次又一次地聽到的是，該藥物基於非常具體的作用機制，具有卓越的安全性，並且有信心不僅可以治療成人，而且現在還可以治療更年輕的年齡組，例如，在特應性皮膚炎方面，不僅可以治療青少年，還可以治療低至 6 歲的兒科患者。

So I think it's a great question, and it reflects back on this issue about penetration and so forth. It didn't take much market research to know how Dupixent was initially being used or how most drugs are used. Though it was approved, for example, in the moderate to severe population, atopic dermatitis, all physicians initially started with their toughest, their hardest, their more serious patients, before then gradually going backwards in the treatment paradigm. And that is one of the reasons why we're only penetrating about 6% of the moderate to severe population. So I think that, gradually with more confidence, they're going to treat people who are on the more moderate side of things.

所以我認為這是一個很好的問題，它也引出了關於藥物滲透率等問題。其實不需要太多的市場調查就能知道Dupixent最初的使用情況，或者說大多數藥物的使用情況。例如，雖然它獲準用於治療中度至重度異位性皮膚炎，但所有醫生最初都是先用它來治療病情最嚴重、最棘手的患者，然後才逐漸調整治療方案。這也是為什麼我們目前在中度至重度異位性皮膚炎患者的滲透率只有6%左右的原因之一。所以我認為，隨著信心的增強，醫生們會逐漸開始用它來治療病情較輕的病人。

That said, I think the point that the efficacy profile, but also the mechanism of action. The fact that you are probably, in the long term, may be benefiting the patient in terms of slowing or preventing the ultimate atopic march that occurs in so many patients, demands that we figure out a way to take this product to earlier patients. Those will, however, require additional studies.

也就是說，我認為關鍵在於療效以及作用機轉。從長遠來看，該產品可能有助於減緩或阻止許多患者最終出現的異位性皮膚炎進展，因此我們必須找到方法讓更早的患者也能使用該產品。然而，這需要進行更多研究。

We're trying to figure out the best way to do it, but I for one do think that, for example, many more patients with much milder asthma or other milder forms of type 2 disease, that we know in many patients is just going to get worse over time, we owe these patients. We have to figure out, through a clinical program, how to do the right studies, how to convince the FDA and how to move this treatment back towards these earlier patients.

我們正在努力尋找最佳方案，但我個人認為，例如，對於許多患有較輕哮喘或其他較輕型2型疾病的患者（我們知道，這些患者的病情會隨著時間推移而惡化），我們有責任為他們提供幫助。我們必須透過臨床試驗項目，找到進行正確研究的方法，說服FDA，並讓這些早期患者能夠獲得治療。

Thanks, everyone, for joining the call. Thank you for hanging in there a little longer than normal. Bob Landry and the Investor Relations team will be around after the call. We hope you enjoy your weekend. Please stay safe.

感謝各位參加本次電話會議。感謝大家比平常多堅持了一段時間。鮑勃·蘭德里和投資者關係團隊將在會議結束後繼續為您服務。祝您週末愉快，注意安全。

Ladies and gentlemen, this does conclude the program. You may now disconnect. Everyone, have a great day.

女士們、先生們，節目到此結束。你們現在可以斷開連結了。祝大家今天過得愉快。