雷傑納榮製藥 (REGN) 2021 Q3 法說會逐字稿

Good day, and thank you for standing by. Welcome to the Regeneron Pharmaceuticals Third Quarter Earnings Conference Call. (Operator Instructions) Please be advised that today's conference is being recorded. (Operator Instructions)

各位好，感謝您的耐心等待。歡迎參加再生元製藥公司第三季財報電話會議。 （操作說明）請注意，本次會議正在錄音。 （操作說明）

I would now like to hand the conference over to your speaker today, Justin Holko, Vice President of Investor Relations. Please go ahead.

現在我謹將會議交給今天的演講嘉賓，投資者關係副總裁賈斯汀·霍爾科。請開始吧。

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

謝謝Didi。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年第三季電話會議。本次網路直播的存檔將在我們的網站上提供。今天與我一同參加電話會議的有：創辦人、總裁兼執行長Leonard Schleifer博士；共同創辦人、總裁兼首席科學官George Yancopoulos博士；執行副總裁兼商務主管Marion McCourt；以及執行副總裁兼財務長Bob Landry。在我們發言結束後，我們將進入問答環節。

I would also like to remind you that remarks made on today's call include forward-looking statements about Regeneron. Such statements may include, but are not limited to, those related to Regeneron and its products and 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 and competition. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission including its Form 10-Q for the period ended September 30, 2021, which we filed with the SEC earlier today. Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

我還要提醒各位，今天電話會議的發言包含Regeneron的前瞻性聲明。這些陳述可能包括但不限於與Regeneron及其產品和業務、財務預測和指引、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、未決訴訟及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，包括我們今天早些時候向美國證券交易委員會提交的截至2021年9月30日的10-Q表格。 Regeneron不承擔任何更新任何前瞻性聲明的義務，無論是因為新資訊、未來事件或其他原因。

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

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

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

接下來，我將把電話交給我們的總裁兼執行長倫·施萊弗博士。

Thank you, Justin. And before I begin my remarks, let me just note that this may be Justin's last call, it may not be, at least in the position of IR. He is making a transition. He has decided he wants to make the news, not just report and explain the news and he is moving over to our commercial organization. So we're very excited, but we're not letting him go until his replacement is fully in place. So you may hear more from Justin in this role what you may not. He -- Justin has done a remarkable job. He is quick to point out to me that when he joined the company, the stock was only around $300. And now he says it's significantly higher. Justin, we thank you for your great service.

謝謝你，賈斯汀。在我開始發言之前，我想先說明一下，這可能是賈斯汀最後一次出席會議，也可能不是，至少在他擔任投資人關係經理這個職位上是這樣。他正在進行職業轉型。他決定不再只是報導和解釋新聞，而是要成為新聞的創造者，所以他將轉到我們的商業部門。我們對此感到非常興奮，但在他的繼任者完全到位之前，我們不會讓他離開。因此，你可能會聽到更多關於賈斯汀在這個職位上的消息，也可能不會。賈斯汀的工作非常出色。他很快就告訴我，他剛加入公司時，股價只有300美元左右。而現在，他說股價已經大幅上漲。賈斯汀，我們感謝你為公司做出的卓越貢獻。

Turning to our business, we turned in another strong performance in the third quarter, which was marked by significant double-digit top and bottom line growth and continued operating leverage. This was more possible as a result of the truly exceptional execution by our colleagues across the entire company from R&D to production, commercial and support teams despite the challenges that we all faced imposed by the COVID-19 pandemic.

就業務而言，我們在第三季度再次取得了強勁的業績，營收和利潤均實現了兩位數的顯著增長，並保持了持續的營運槓桿效應。這主要歸功於公司全體同事，從研發到生產、銷售和支援團隊，儘管面臨新冠疫情帶來的挑戰，他們依然展現了卓越的執行力。

Our core business of EYLEA, Dupixent and Libtayo, all contributed solid underlying growth. Additionally, we secured a third supply agreement with the United States government for REGEN-COV, our investigational antibody cocktail for treating and preventing COVID-19 in certain populations with initial deliveries fueling additional growth momentum in the quarter.

我們的核心業務，包括安永（EYLEA）、度普利（Dupixent）和利必妥（Libtayo），均貢獻了穩健的基礎成長。此外，我們與美國政府簽署了第三份供應協議，為正在研發的抗體雞尾酒療法REGEN-COV提供藥物，該療法用於治療和預防特定人群的COVID-19感染。首批交付將推動本季業績的進一步成長。

In R&D, our broad and growing pipeline, which now includes more than 30 clinical stage candidates with many more expected to enter the clinic in short order continues to advance new innovations to secure our long-term growth potential. Importantly, our pipeline continues to be largely composed and comprised of internal innovation. But increasingly, it is supplemented by external relationships that bring in novel modalities, including CRISPR and siRNA, creating unique treatment options and combination approaches as George will outline momentarily.

在研發方面，我們不斷拓展的研發管線目前包含30多個處於臨床階段的候選藥物，預計不久的將來還會有更多藥物進入臨床試驗階段，這些創新將持續推進，確保我們的長期成長潛力。值得注意的是，我們的研發管線仍主要由內部創新所構成。但同時，我們也越來越多地透過外部合作引入新的治療模式，例如CRISPR和siRNA，從而創造出獨特的治療方案和聯合療法，喬治稍後將對此進行詳細介紹。

In the third quarter, beginning with EYLEA, global net sales of EYLEA were $2.4 billion, growing 15% compared to the prior year. U.S. EYLEA sales grew 12%, reflecting recovery of the anti-VEGF category and share gains as the leading anti-VEGF treatment for retinal diseases. We see the strength of EYLEA an opportunity for steady growth continuing despite potential upcoming competition from which we currently do not see any disruptive or game-changing new engines to the anti-VEGF space for treating retinal diseases.

第三季度，以EYLEA為例，其全球淨銷售額達24億美元，較去年同期成長15%。其中，EYLEA在美國的銷售額成長12%，反映出抗VEGF藥物市場的復甦以及其作為治療視網膜疾病的領先抗VEGF藥物所取得的市佔率成長。儘管未來可能面臨一些競爭，但我們認為EYLEA的強勁表現為其持續穩定成長提供了機會。目前，我們尚未看到任何顛覆性或顛覆性的新產品或技術能夠撼動治療視網膜疾病的抗VEGF藥物市場。

Dupixent continues to be remarkable in delivering commercially and clinically across a wide spectrum of type 2 inflammatory diseases. In the third quarter, global net sales grew 55% to $1.7 billion. Growth contributions from inside and outside of the United States continued to improve operating leverage in our alliance with Sanofi.

Dupixent在治療多種第2型發炎性疾病方面，無論在商業上或臨床上，都持續展現出卓越的療效。第三季度，全球淨銷售額成長55%，達到17億美元。來自美國境內外的成長貢獻持續提升了我們與賽諾菲聯盟的營運槓桿。

Moreover, we announced positive results from 4 Phase III registrational studies in recent months, 1 in very young children with atopic dermatitis, and 3 in the potential new indications of eosinophilic esophagitis, prurigo nodularis and chronic spontaneous urticaria.

此外，我們最近幾個月公佈了 4 項 III 期註冊研究的積極結果，其中 1 項針對患有異位性皮膚炎的幼兒，3 項針對嗜酸性食道炎、結節性癢疹和慢性自發性蕁麻疹這三種潛在的新適應症。

In October, the FDA expanded our asthma label to include children aged 6 to 11, a testament to not only the efficacy, but also the safety of Dupixent in the chronic treatment of type 2 inflammatory diseases. With several other disease opportunities in clinical development, such as COPD, the expansion possibilities are significant for this remarkable medicine that is already changing the lives of hundreds of thousands of patients.

10月，FDA擴大了Dupixent的適應症範圍，將6至11歲的兒童納入其中，不僅證明了Dupixent在治療第二型發炎性疾病的療效，也證明了其安全性。目前，Dupixent正處於其他多種疾病的臨床開發階段，例如慢性阻塞性肺病（COPD），其適應症的拓展前景十分廣闊，這款卓越的藥物已經改變了數十萬患者的生活。

In Oncology, Libtayo global net sales were $120 million and grew 24%. Despite the challenges imposed on the Oncology market by COVID-19, we're working hard as the leader in cutaneous squamous cell carcinoma and progressing in our basal cell carcinoma and lung cancer launches. We are also preparing for a potential launch in 2022 in the much larger opportunity of Libtayo combined with chemotherapy in non-small cell lung cancer.

在腫瘤領域，Libtayo的全球淨銷售額為1.2億美元，成長了24%。儘管新冠疫情為腫瘤市場帶來了挑戰，但我們作為皮膚鱗狀細胞癌的領導者，正努力保持領先地位，並在基底細胞癌和肺癌的上市方面取得進展。此外，我們也積極籌備，並計劃於2022年推出Libtayo聯合化療用於治療非小細胞肺癌，這蘊藏著更大的市場機會。

REGEN-COV continues to grow in importance with increased utilization in the treatment of COVID-19. The FDA has accepted under priority review our biologic license application for the treatment and prophylaxis of COVID-19 in certain patients. We are also on review to expand the emergency use authorization for REGEN-COV in certain hospitalized patients and for pre-exposure prophylaxis.

隨著REGEN-COV在COVID-19治療的應用日益廣泛，其重要性也與日俱增。 FDA已受理我們用於治療和預防特定患者COVID-19的生物製品許可申請，​​並給予優先審查資格。此外，我們正在申請擴大REGEN-COV的緊急使用授權範圍，用於特定住院患者以及暴露前預防。

Outside of the United States, our antibody cocktail has received a full approval in Japan, is conditionally approved in Australia and the U.K., and has emergency or temporary pandemic authorizations currently in place in more than 40 other countries.

在美國以外，我們的抗體雞尾酒療法已在日本獲得全面批准，在澳洲和英國獲得有條件批准，並在其他 40 多個國家/地區獲得緊急或臨時疫情授權。

REGEN-COV has the potential for a broad range of prevention and treatment applications from preexposure prophylaxis to treatment of infected hospitalized patients. Given the anticipation of new COVID infections over time, increased utilization of REGEN-COV in appropriate cases and the need for prophylaxis in immunocompromised individuals, we anticipate an ongoing role for REGEN-COV. If global demand warrants, we have the capacity to produce between 4 million to 5 million 1.2 gram doses in 2022, excluding any further supply contributions from Roche.

REGEN-COV 具有廣泛的預防和治療應用潛力，涵蓋從暴露前預防到感染住院患者的治療。鑑於未來 COVID-19 感染病例預計持續增加，REGEN-COV 在適當情況下的使用量將持續提高，以及免疫功能低下族群的預防需求，我們預計 REGEN-COV 將繼續發揮作用。如果全球需求旺盛，我們有能力在 2022 年生產 400 萬至 500 萬劑 1.2 克裝的 REGEN-COV，這還不包括羅氏公司提供的額外供應。

To conclude, as we close out 2021, our growth momentum is strong and our outlook for continued growth fueled by the breadth and depth of our pipeline is bright. Now I will turn the call over to George.

總之，在2021年即將結束之際，我們的成長勢頭強勁，憑藉我們廣泛而深入的產品線，我們對未來的持續成長前景充滿信心。現在，我將把電話交給喬治。

Thank you, Len. I'll pick up where you left me with the REGEN-COV story. As Len mentioned, our robust COVID-19 development program involving more than 25,000 people to date has provided compelling evidence that REGEN-COV has the potential to be used for various prevention and treatment applications from pre-exposure prophylaxis to treating hospitalized patients. In the United States, REGEN-COV is currently authorized under an EUA and also being reviewed for full FDA approval for the treatment and prevention of COVID-19 in certain patients with an action date of April 13, 2022. At Regeneron, we all appreciate that widespread vaccination is the best way to broadly protect as many people as possible from COVID-19. But recent research also reveals some important gaps in coverage provided by the vaccines, leaving some individuals uniquely vulnerable, particularly the several million immunocompromised people in the United States alone who remain prisoners of the pandemic.

謝謝Len。我接著你剛才說的REGEN-COV的情況繼續講。正如Len所提到的，我們迄今為止已開展了一項強大的COVID-19研發項目，該項目已招募了超過25,000名志願者，並提供了令人信服的證據，表明REGEN-COV具有用於多種預防和治療用途的潛力，從暴露前預防到治療住院患者。在美國，REGEN-COV目前已獲得緊急使用授權（EUA），並且正在接受FDA的全面批准審查，用於治療和預防特定患者的COVID-19，預計審批日期為2022年4月13日。在Regeneron，我們都認為廣泛接種疫苗是保護盡可能多的人免受COVID-19侵害的最佳方法。但最近的研究也揭示了疫苗覆蓋範圍存在一些重要的缺口，使一些人群特別容易受到感染，尤其是在美國，數百萬免疫功能低下的人仍然深受疫情。

First, many of the immunocompromised population respond sub-optimally or not at all to vaccination, even after booster shots. Second, breakthrough infections in the general population still occur after vaccination, meaning that immunocompromised people will continue to be at risk of encountering infected individuals even within a highly vaccinated population. Therefore, we believe that REGEN-COV could be of particular importance for these immunocompromised individuals who remain unprotected and also are at highest risk for developing the most severe COVID-19 disease. This includes people with certain hematologic cancers, for example, lymphomas, leukemias and myeloma and people who take certain immunosuppressive medicines for diseases such as multiple sclerosis, in rheumatoid arthritis, for organ transplant recipients and for those with primary immunodeficiencies.

首先，許多免疫功能低下族群即使接種加強劑後，對疫苗的反應也不佳或完全無效。其次，即使接種了疫苗，一般人群中仍會發生突破性感染，這意味著即使在疫苗接種率很高的群體中，免疫功能低下者仍然面臨接觸感染者的風險。因此，我們認為 REGEN-COV 疫苗對於這些尚未獲得保護且極易發展為重症 COVID-19 的免疫功能低下人群尤其重要。這包括患有某些血液系統癌症（例如淋巴瘤、白血病和骨髓瘤）的患者，以及服用某些免疫抑制劑治療多發性硬化症、類風濕性關節炎等疾病的患者、器官移植受者以及原發性免疫缺陷患者。

In the United States, Regeneron submitted data and a request to the FDA to expand the existing emergency use authorization of REGEN-COV to include chronic prevention back in April. Further reflecting Regeneron's commitment to the immunocompromised, we recently began a big trial to optimize REGEN-COV prophylaxis in this population, including evaluation of extended dose.

在美國，Regeneron公司於今年4月向FDA提交了數據和申請，希望擴大REGEN-COV的現有緊急使用授權範圍，使其涵蓋慢性病預防。為了進一步體現Regeneron對免疫功能低下族群的承諾，我們近期啟動了一項大型試驗，旨在優化REGEN-COV在該族群中的預防效果，包括評估延長給藥時間。

Our current REGEN-COV cocktail retains potent activity against all known variants of interest, including the Delta variant. However, the virus continues to mutate and evolve. And thus, as we have previously discussed, we are advancing a novel anti-spike protein antibody cocktail into clinical development. We have done so proactively in the case of a novel innovative antibody cocktail that retains potency against new potential variants as required in the future.

我們目前的 REGEN-COV 抗體雞尾酒療法對所有已知的目標變異株（包括 Delta 變異株）均保持強效活性。然而，病毒仍在不斷變異和進化。因此，正如我們之前討論過的，我們正在推進一種新型抗刺突蛋白抗體雞尾酒療法的臨床開發。我們之所以採取這種積極主動的策略，是為了研發一種能有效對抗未來可能出現的新變異株的創新抗體雞尾酒療法。

Moving to Ophthalmology. We reported encouraging top line data of high-dose aflibercept in the Phase II CANDELA study in wet AMD. The small proof-of-concept study met its primary efficacy endpoint, a higher proportion of patients in the 8-milligram aflibercept group had no retinal fluid compared to patients treated with the currently approved 2-milligram EYLEA dose at week 16.

接下來是眼科方面。我們報告了高劑量阿柏西普治療濕性老年黃斑部病變（AMD）的II期CANDELA研究的令人鼓舞的初步數據。這項小型概念驗證研究達到了其主要療效終點，即在第16週時，8毫克阿柏西普組中無視網膜積液的患者比例高於目前已獲批准的2毫克EYLEA劑量組。

There were no safety signals observed in the comparison to the currently approved EYLEA 2-milligram dose, 2 large Phase III trials in wet AMD and DME, evaluating the high dose of aflibercept in dosing intervals of every 12 weeks and every 16 weeks are fully enrolled and are expected to report results in the second half of 2022. These Phase III data will be crucial to understanding overall efficacy, safety and convenience of high dose aflibercept.

與目前已批准的 EYLEA 2 毫克劑量相比，未觀察到任何安全性訊號。兩項大型 III 期臨床試驗分別評估了每 12 週和每 16 週給藥間隔的高劑量阿柏西普在濕性 AMD 和 DME 中的療效，目前已完成全部受試者招募，預計將於 2022 年下半年公佈結果。這些 III 期臨床試驗數據對於了解高劑量阿柏西普的整體療效、安全性和便利性至關重要。

Moving on to Dupixent. The remarkable clinical success of Dupixent across so many different allergic or type 2 inflammatory diseases, validates our early and long-standing hypothesis that these conditions are all driven by overactivation of the same fundamental immunologic pathway that is the interleukin-4 and interleukin-13 pathway, which is effectively blocked by Dupixent whether the disease manifests as asthma or chronic [rhinositis] with nasal polyps in the airways as atopic dermatitis or prurigo nodularis in the skin, as the eosinophilic esophagitis in the GI tract. Our clinical data have demonstrated an important impact of Dupixent on these many conditions that initially did not seem related. In only the past few months, Dupixent demonstrated positive results in 4 separate pivotal studies. This is a tremendous accomplishment stemming from the vision and dedication of our team and it's great news for patients suffering from these type 2 inflammatory diseases.

接下來談談Dupixent。 Dupixent在眾多不同的過敏性疾病或2型發炎性疾病中取得的顯著臨床成功，驗證了我們早期且長期的假設：這些疾病均由同一基本免疫路徑（即白細胞介素-4和白細胞介素-13通路）的過度活化所驅動。無論疾病表現為氣喘或伴隨鼻息肉的慢性鼻炎，或是異位性皮膚炎或結節性癢疹等皮膚疾病，亦或是嗜酸性食道炎等胃腸道疾病，Dupixent都能有效阻斷該通路。我們的臨床數據表明，Dupixent對這些最初看似無關的多種疾病均有顯著療效。僅在過去幾個月裡，Dupixent就在4項關鍵性研究中取得了積極成果。這源自於我們團隊的遠見卓識和不懈努力，也是2型發炎性疾病患者的福音。

In a recent Phase III trial in atopic dermatitis in infants and children as young as 6 months of age, Dupixent met all primary and secondary endpoints as well as a lower observed rate of skin infections in the Dupixent group compared to placebo.

在最近一項針對 6 個月大嬰兒和兒童異位性皮膚炎的 III 期試驗中，Dupixent 達到了所有主要和次要終點，並且與安慰劑組相比，Dupixent 組的皮膚感染率也較低。

Detailed results from this trial will be presented at a future medical meeting, and data will be submitted to the FDA by the end of this year. These data reinforce the well-established efficacy and safety profile of Dupixent with over 0.5 million patients treated to date. We also reported recent Phase III data with Dupixent in eosinophilic esophagitis or EoE, a progressive disease that damages the esophagus and impairs the ability to swallow. More than 1/3 of the patients in our trial had manifestations of this disease so severe that they previously had to undergo endoscopic dilation of the esophagus for symptomatic relief. In our study, patients taking weekly Dupixent had an approximate 24-point improvement on the 0 to 84 dysphagia symptom questionnaire, representing a 64% improvement compared to a 14-point improvement for placebo.

該試驗的詳細結果將在未來的醫學會議上公佈，數據將於今年底提交給FDA。這些數據進一步證實了Dupixent已確立的療效和安全性，迄今已有超過50萬名患者接受了該藥物治療。我們也報告了Dupixent治療嗜酸性粒細胞性食道炎（EoE）的最新III期臨床試驗數據。 EoE是一種進行性疾病，會損害食道並影響吞嚥功能。在我們試驗中，超過三分之一的患者病情嚴重，先前曾接受過內視鏡食道擴張術以緩解症狀。在我們的研究中，每週服用Dupixent的患者在0至84分的吞嚥困難症狀問卷中平均改善了約24分，與安慰劑組相比，改善率達64%（安慰劑組改善14分）。

This update reinforced previously reported Phase III results for which the 52-week follow-up results were recently presented at the United European Gastroenterology Week Virtual 2021 Congress. Completion of our regulatory filing for EoE in adolescents and adults is planned for early 2022. We also recently reported positive results for Dupixent from our Phase III trial in yet another inflammatory skin condition known as prurigo nodularis, an underdiagnosed disease characterized by extreme itch and skin nodules. The trial met its primary and all key secondary endpoints in comparison to placebo, including reduction in itch from baseline at 12 and 24 weeks, achieving clear skin and improvement in quality of life. A second trial in prurigo nodularis is fully enrolled and is expected to read out in the first half of '22 with regulatory submissions planned for the same year.

此次更新進一步證實了先前發表的III期臨床試驗結果，其中52週追蹤結果已於近期在2021年歐洲聯合胃腸病學週虛擬大會上發布。我們計劃於2022年初完成青少年和成人嗜酸性粒細胞性食道炎（EoE）的監管申報。此外，我們近期也發表了Dupixent在另一種發炎性皮膚病－結節性癢疹（一種以劇烈搔癢和皮膚結節為特徵的診斷不足的疾病）的III期臨床試驗中的積極結果。與安慰劑相比，該試驗達到了主要終點和所有關鍵次要終點，包括在第12周和第24週時瘙癢程度較基線有所減輕、皮膚完全清除以及生活品質的改善。另一項針對結節性癢疹的試驗已完成全部受試者招募，預計將於2022年上半年公佈結果，併計劃於同年提交監管申報。

If all these exciting Phase III data lead to regulatory approvals, Dupixent would be approved for 6 different allergic or type 2 inflammatory disease indications, including patients as young as 6 months.

如果所有這些令人興奮的 III 期數據最終獲得監管部門的批准，Dupixent 將獲準用於治療 6 種不同的過敏性疾病或 2 型發炎性疾病，包括 6 個月大的患者。

Moving to Libtayo in Oncology. Positive Phase III data of Libtayo in combination with chemotherapy in first-line advanced non-small cell lung cancer were presented at the ESMO 2021 meeting. These data mark Libtayo as 1 of only 2 PD-1 or PD-L1 inhibitors to demonstrate positive Phase III results in first line non-small cell lung cancer, irrespective of histology, both as monotherapy and in combination with chemotherapy. These Libtayo studies were conducted in a patient population that included difficult-to-treat disease characteristics that reflects everyday clinical practice. We are rapidly progressing towards regulatory submission for the Libtayo chemotherapy combination across histologies and PD-L1 expression levels, which could unlock an opportunity to help a larger population of lung cancer patients.

Libtayo在腫瘤治療領域取得進展。在2021年ESMO年會上，Libtayo合併化療第一線治療晚期非小細胞肺癌的III期臨床試驗數據已發表。這些數據表明，Libtayo是目前僅有的兩種在非小細胞肺癌一線治療中，無論組織學類型如何，單藥治療或聯合化療均取得陽性III期臨床試驗結果的PD-1或PD-L1抑制劑之一。 Libtayo的這些研究納入了具有難治性疾病特徵的患者群體，反映了日常臨床實踐。我們正快速推進Libtayo聯合化療方案的監管審批，該方案適用於各種組織學類型和PD-L1表達水平，預計將為更多肺癌患者帶來福音。

Turning to Hematology. At the upcoming American Society of Hematology Annual Meeting for ASH, we will provide updates to our developing Hematology portfolio. The nodal presentation we will provide a data update for our potentially registrational first-in-human trial of REGN5458. Our BCMA by CD3 bispecific antibody tested in patients with heavily pretreated multiple myeloma. REGN5458 to be a major advance in treatment of patients who have failed several prior lines of therapy, but the potential utility of our BCMA-targeted bispecific is not limited to this patient population. We will discuss our data and further development plans at our virtual ASH Investor event scheduled for Monday, December 13 regarding odronextamab or CD20 by CD3 bispecific. We are pleased with our -- with recruitment in our potentially pivotal trial since the partial clinical hall was lifted earlier this year. Exploration of subcutaneous formulation of odronextamab is on track to start by the end of this year. We are planning to initiate broader Phase III programs in 2022.

接下來談談血液學領域。在即將舉行的美國血液學會年會（ASH）上，我們將介紹我們正在開發的血液學產品組合的最新進展。在主題演講中，我們將提供REGN5458（一種針對BCMA和CD3的雙特異性抗體）潛在註冊性首次人體試驗的最新數據。 REGN5458已在接受過大量預先治療的多發性骨髓瘤患者中進行了測試。 REGN5458有望成為治療既往接受過多種療法失敗患者的一項重大突破，但我們這種針對BCMA的雙特異性抗體的潛在用途並不局限於此類患者群體。我們將在12月13日（星期一）舉行的ASH線上投資者活動上討論odronextamab（一種靶向CD20和CD3的雙特異性抗體）的數據和後續研發計劃。我們對這項潛在關鍵性試驗的招募進展感到滿意，因為今年稍早部分臨床試驗限制已經解除。 odronextamab皮下製劑的探索工作正按計畫進行，預計今年底啟動。我們計劃在2022年啟動更廣泛的III期臨床試驗計畫。

Our bispecific development program for solid tumors is progressing with our unique approaches, including the MUC16xCD3 bispecific as monotherapy in ovarian cancer as well as in combination with Libtayo or with our MUC16xCD28 costim. In addition, we expect to have initial data with our PSMAxCD28 costim in patients with prostate cancer in '22.

我們針對實體瘤的雙特異性抗體開發項目正採用我們獨特的方法穩步推進，其中包括MUC16xCD3雙特異性抗體作為卵巢癌單藥療法以及與Libtayo或我們的MUC16xCD28共刺激藥物聯合治療。此外，我們預計2022年獲得PSMAxCD28共刺激藥物在前列腺癌患者的初步數據。

We are also excited about our EGFRxCD28 costim clinical program across multiple EGF high cancer settings, including lung cancer as well as our clinical stage METxMET bispecific and our METxMET antibody drug conjugate, presenting a new (inaudible) for Regeneron into the realm of drug conjugates linked to our potentially best in class bispecific antibodies.

我們也對我們的 EGFRxCD28 共刺激臨床項目感到興奮，該項目涵蓋多種 EGF 高表達癌症，包括肺癌；此外，我們的臨床階段 METxMET 雙特異性抗體和 METxMET 抗體藥物偶聯物，為 Regeneron 進入與我們潛在的同類雙特異性抗體相連的藥物偶聯物領域帶來了新的進展（聽不清）。

In conclusion for Oncology, we are approaching an important new phase for Regeneron. We have several novel Phase I/II programs in clinical development with more expected in the coming months. We also have large Phase III studies planned such as our LAG-3 Libtayo for first-line advanced melanoma against the pembrolizumab monotherapy comparator as well as large registrational programs for our Hematology/Oncology bispecifics. We're excited about the potential that these important investments in our portfolio may bring to patients.

總之，在腫瘤領域，Regeneron 正邁入一個重要的全新階段。我們目前有多個處於臨床開發階段的新型 I/II 期項目，預計未來幾個月將有更多項目啟動。此外，我們也計劃進行大型 III 期研究，例如針對第一線治療晚期黑色素瘤的 LAG-3 Libtayo 計畫（與帕博利珠單抗單藥治療對照），以及針對血液/腫瘤雙特異性抗體的大型註冊研究。我們對這些重要的投資可能為患者帶來的益處感到無比興奮。

I would like to conclude with our Regeneron genetics medicines in our collaboration updates. We are uniquely positioned to combine products of our established biologics portfolio and emerging findings from our genetics medicine efforts. As part of our collaboration with Alnylam, we are looking forward to multiple updates on our C5 program. As we already mentioned ASH meeting, we will show first-in-human data for our C5 antibody, pozelimab in combination with the C5 inhibiting siRNA, cemdisiran. We will present initial results in healthy volunteers, which supports development of this first-of-its-kind combination of an antibody and an siRNA therapeutic. Early data on siRNA monotherapy mediated C5 (inaudible) did not achieve complete terminal complement blockade, which is necessary for adequate disease control in PNH or paroxysmal nocturnal hematuria. Adding the antibody specific for the same target protein could provide patients with a lower dose therapy and a more convenient extended dosing regimen while providing more complete C5 inhibition, resulting in better efficacy and less breakthrough hemolysis.

最後，我想談談我們Regeneron基因藥物在合作進展的最新情況。我們擁有獨特的優勢，能夠將我們成熟的生物製劑產品組合與我們在基因藥物研發方面的最新發現相結合。作為與Alnylam合作的一部分，我們期待在C5專案上取得多項進展。正如我們在ASH會議上提到的，我們將展示我們的C5抗體pozelimab與C5抑制siRNA cemdisiran聯合用藥的首次人體試驗數據。我們將展示健康志願者的初步結果，這些結果支持開發這種首創的抗體和siRNA聯合療法。早期數據顯示，siRNA單一藥物治療C5（聽不清楚）未能達到完全的末端補體阻斷，而這對於有效控制陣發性睡眠性血紅素尿症（PNH）的病情至關重要。添加針對同一標靶蛋白的抗體可為患者提供更低劑量、更便利的延長給藥方案，同時提供更徹底的C5抑制，進而提高療效並減少突破性溶血的發生。

We have also recently initiated a Phase III study testing the C5 antibody and siRNA combination in myasthenia gravis. For PNH, starting next year, we are planning to test our combo in both naive and switch patients tested against standard of care therapies, including ravulizumab and eculizumab. This study has the potential to show a true benefit of the combination approach for the treatment of this disease.

我們近期啟動了一項III期臨床試驗，旨在測試C5抗體和siRNA聯合療法在重症肌無力中的療效。對於陣發性睡眠性血紅蛋白尿症（PNH），我們計劃從明年開始，在初治患者和轉換治療患者中測試該聯合療法，並將其與包括ravulizumab和eculizumab在內的標準療法進行比較。這項研究有望證實該聯合療法在治療該疾病方面的真正優勢。

Also in collaboration with Alnylam, some of our initial genetic target discoveries are reaching the stage of clinical readouts for nonalcoholic steatohepatitis or NASH, a disease where finding compelling treatment options has been difficult. We're using the siRNA approach to silence the gene we identified as a potential target. Recall, we discovered that people with a protective HSD17B13 gene variant have a 30% to 70% lower odds of chronic liver disease. Our collaborator, Alnylam, will show initial healthy volunteer safety data for the Alnylam HSD, the HSD17B13 targeting siRNA at their upcoming R&D Day later this month.

此外，我們與Alnylam公司合作，一些我們最初發現的基因標靶正進入非酒精性脂肪性肝炎（NASH）的臨床試驗階段。 NASH是一種難以找到有效治療方案的疾病。我們採用siRNA技術來沉默我們所確定的潛在標靶基因。先前，我們發現攜帶HSD17B13保護性基因變異的族群罹患慢性肝病的風險降低了30%至70%。我們的合作夥伴Alnylam公司將在本月稍後舉行的研發日活動上公佈針對HSD17B13的siRNA——Alnylam HSD——的初步健康志工安全性數據。

Finally, in October, the Regeneron Genetics Center published a manuscript in nature, which highlighted achievement of the milestone of sequencing almost 0.5 million exomes from the U.K. Biobank database. This nature paper for the first time describes rare variants of genes that could be potential drug targets for diseases such as hypertension, diabetes, asthma and others.

最終，在10月份，再生元遺傳學中心在《自然》雜誌上發表了一篇論文，重點介紹了其完成英國生物銀行資料庫中近50萬個外顯子組定序這一里程碑式的成就。這篇《自然》論文首次描述了基因的罕見變異，這些變異可能成為高血壓、糖尿病、氣喘等疾病的潛在藥物標靶。

And with that, I will turn the call over to Marion.

接下來，我將把電話交給瑪莉安。

Thank you, George. Our third quarter business performance demonstrates the strength of our commercial portfolio. We are executing well on our in-line brands and are maximizing opportunities for diversified and sustainable growth through ongoing launches.

謝謝你，喬治。我們第三季的業績表現充分展現了我們商業組合的實力。我們旗下現有品牌運作良好，並透過持續推出新產品，最大限度地把握多元化和永續成長的機會。

First, I will highlight recent achievements with REGEN-COV, our COVID-19 antibody cocktail, which is available in the U.S. under emergency use authorization by the FDA. In the third quarter, U.S. net sales were $677 million, primarily based on the initial deliveries of our third government agreement, which was announced in mid-September. Demand for REGEN-COV accelerated sharply over the third quarter as this promising treatment option continues to help fight the surge in COVID-19 cases. REGEN-COV is increasingly seen as standard of care for outpatient treatment and post-exposure prophylaxis in appropriate patients. Our field educators continue to support key stakeholders in health care systems at administration sites.

首先，我將重點介紹我們新冠抗體雞尾酒療法 REGEN-COV 的最新進展。該療法已獲得美國食品藥物管理局 (FDA) 的緊急使用授權，並在美國上市。第三季度，REGEN-COV 在美國的淨銷售額為 6.77 億美元，主要得益於 9 月中旬宣布的第三份政府協議的首批交付。隨著這一前景廣闊的治療方案持續幫助對抗新冠病例激增，REGEN-COV 的需求在第三季急劇增長。 REGEN-COV 正日益被視為門診治療和暴露後預防的標準療法，適用於合適的患者。我們的現場培訓人員將繼續在各醫療機構的給藥點為關鍵利害關係人提供支援。

While COVID-19 cases have thankfully decreased over the last several weeks, demand for REGEN-COV remains high with many patients receiving treatment. REGEN-COV has broad therapeutic application in current and potential future integrations across the spectrum of disease from pre-exposure prevention to hospitalization. We look forward to the FDA's decision on our application for a full approval expected in April of 2022.

儘管過去幾週新冠肺炎病例有所減少，但對 REGEN-COV 的需求仍然很高，許多患者正在接受治療。 REGEN-COV 在疾病的各個階段都具有廣泛的治療應用前景，從暴露前預防到住院治療，均可應用於當前及未來的潛在治療方案中。我們期待 FDA 於 2022 年 4 月對我們的全面批准申請做出決定。

Beyond REGEN-COV, we delivered strong growth from our core business in the third quarter. Starting with EYLEA, third quarter global net sales grew 15% year-over-year to more than $2.4 billion. In the U.S., net sales grew 12% year-over-year to nearly $1.5 billion based on category recovery and EYLEA's competitor share gains. EYLEA secured nearly 50% of the overall category and over 75% of the branded category based on our overall platform of efficacy, safety and convenience.

除了REGEN-COV之外，我們的核心業務在第三季也實現了強勁成長。以EYLEA為例，第三季全球淨銷售額年增15%，超過24億美元。在美國，得益於品類復甦和EYLEA市佔率的提升，淨銷售額年增12%，接近15億美元。 EYLEA憑藉其卓越的功效、安全性和便利性，佔據了近50%的品類市場份額和超過75%的品牌藥品類市場份額。

There are positive early indicators from our unbranded direct-to-consumer campaign that educates patients with diabetic eye disease on the importance of vision care. Retina specialists have applauded our efforts encouraging diabetic patients to seek treatment to prevent irreversible vision loss.

我們面向消費者的非品牌直銷活動已初見成效，該活動旨在教育糖尿病眼疾患者視力保健的重要性。視網膜專家對我們鼓勵糖尿病患者尋求治療以防止不可逆視力喪失的努力表示讚賞。

EYLEA's competitive profile, coupled with favorable underlying demographic trends give us confidence in Regeneron's ongoing leadership position in retinal diseases.

EYLEA 的競爭優勢，加上有利的潛在人口趨勢，使我們對 Regeneron 在視網膜疾病領域持續保持領先地位充滿信心。

Turning to Libtayo. Global net sales were $120 million. In the U.S., net sales reached $78 million despite continued COVID impacts on new patient starts. With new indication launches at early stages, the vast majority of sales came from advanced cutaneous squamous cell carcinoma or CSCC, where Libtayo is the #1 systemic treatment. Building on our success in CSCC, we are quickly establishing Libtayo as standard of care in advanced basal cell carcinoma for patients in the second-line setting or where a Hedgehog inhibitor is not appropriate. In lung cancer, we are working to secure a physician experience with Libtayo as a competitive monotherapy treatment option. We look forward to the potential chemotherapy combination approval, which would unlock the much larger group of first-line patients eligible for anti-PD-1.

接下來談談利妥昔單抗（Libtayo）。其全球淨銷售額為1.2億美元。在美國，儘管新冠疫情持續影響新患者數量，但淨銷售額仍達7,800萬美元。由於新適應症的上市尚處於早期階段，利妥昔單抗的絕大部分銷售額來自晚期皮膚鱗狀細胞癌（CSCC），利妥昔單抗是該領域排名第一的全身性治療藥物。基於我們在CSCC領域的成功，我們正迅速將利妥昔單抗確立為晚期基底細胞癌二線治療或不適合使用Hedgehog抑制劑患者的標準治療方案。在肺癌領域，我們正努力讓醫師充分體驗利妥昔單抗作為一種具有競爭力的單藥治療選擇。我們期待其化療合併用藥方案獲得批准，這將使更多符合抗PD-1治療條件的第一線患者受益。

Briefly turning to Evkeeza, which is now being used to treat more patients than the prior standard of care, we continue to see initiations in both switch and new-to-category patients, illustrating how our innovative patient identification efforts can be used to support those with HoFH and in the future, other rare diseases.

簡單來說，Evkeeza 目前用於治療的患者人數已超過先前的標準治療，我們不斷看到轉換治療和新類別治療的患者開始接受治療，這表明我們創新的患者識別工作可以如何用於支持 HoFH 患者，以及未來其他罕見疾病患者。

And finally, to Dupixent, in the third quarter, global net sales grew 55% year-over-year to $1.7 billion and U.S. net sales grew 48% to $1.3 billion. This growth was driven across all approved indications, with new patient starts above pre-COVID levels. In atopic dermatitis, prescribing trends are strong across the spectrum of moderate-to-severe disease, including adolescent and pediatric patients. Dupixent continues to capture market growth based on well-established efficacy and safety, breadth of current indications and unmatched physician and patient experience. There continues to be substantial potential growth in atopic dermatitis, including in children as young as 6 months in age and more broadly in Dermatology with new potential indications of chronic spontaneous urticaria and prurigo nodularis.

最後，關於Dupixent，第三季全球淨銷售額年增55%至17億美元，美國淨銷售額成長48%至13億美元。所有已核准適應症均實現了成長，新患者用藥量也高於新冠疫情前的水準。在異位性皮膚炎領域，Dupixent的處方量在中重度患者中均呈現強勁成長趨勢，包括青少年和兒童患者。 Dupixent憑藉其已確立的療效和安全性、廣泛的現有適應症以及卓越的醫病體驗，持續保持著市場成長勢頭。異位性皮膚炎領域仍具有巨大的成長潛力，包括6個月及以上嬰幼兒，以及更廣泛的皮膚科領域，例如慢性自發性蕁麻疹和結節性癢疹等新的潛在適應症。

In respiratory disease, Dupixent continues to surpass recent competitive biologic launches. In asthma, we see ongoing potential to differentiate Dupixent through its competitive profile and label expansion as the market recovers from COVID, when asthma-related emergency room visits were down nearly 50%. Our launch in pediatric asthma is underway, extending this treatment option to 75,000 children in the U.S. who suffer from this often debilitating disease.

在呼吸系統疾病領域，Dupixent 持續超越其他近期上市的生物製劑。在氣喘領域，隨著市場從新冠疫情中復甦（疫情期間與氣喘相關的急診就診量下降了近 50%），我們看到 Dupixent 憑藉其競爭優勢和適應症擴展，具有持續的差異化潛力。我們正在推動 Dupixent 在兒童氣喘領域的上市，將這項治療選擇帶給美國 75,000 名飽受氣喘折磨的兒童。

Dupixent's label was also recently updated to include an additional marker of type 2 inflammation called pheno, which extends the eligible population beyond those with high eosinophilic levels. In addition, Dupixent can be prescribed for steroid-dependent asthma regardless of eosinophilic levels.

Dupixent的說明書最近也進行了更新，新增了一種名為pheno的2型發炎標記物，這使得適用人群不再局限於嗜酸性粒細胞水平高的患者。此外，無論嗜酸性粒細胞水平如何，Dupixent均可用於治療荷爾蒙依賴性氣喘。

In nasal polyps, we continue to see growth with Dupixent leading the market despite new competition. Dupixent continues to be the preferred choice of ENTs and allergists regardless of prior surgery.

在鼻息肉治療領域，儘管面臨新的競爭，Dupixent 仍保持市場領先地位，銷售持續成長。無論患者之前是否接受過手術，Dupixent 仍然是耳鼻喉科醫生和過敏科醫生的首選藥物。

In summary, our commercial team continues to deliver strong growth across the portfolio with differentiated brands, ongoing and potential future launches, we remain on track for long-term growth. Now, I'll turn the call over to Bob.

總而言之，我們的商業團隊憑藉差異化品牌、正在進行和潛在的未來新品發布，持續推動旗下所有產品組合實現強勁增長，我們仍朝著長期增長目標穩步前進。現在，我將把電話交給鮑伯。

Thank you, Marion. My comments today on Regeneron's financial results and outlook will be on a non-GAAP basis where applicable. In the third quarter, Regeneron once again delivered strong top and bottom line growth on increasingly diversified revenue streams with contributions from REGEN-COV in our robust core business.

謝謝，Marion。今天我對Regeneron財務表現和展望的評論將盡可能採用非GAAP準則。第三季度，Regeneron再次實現了強勁的營收和利潤成長，這得益於我們日益多元化的收入來源，其中REGEN-COV在我們穩健的核心業務中做出了貢獻。

For the third quarter, total revenues grew 51% year-over-year to $3.5 billion. Total diluted net income per share grew 84% year-over-year to $15.37 on net income of $1.8 billion. Excluding revenues related to the COVID-19 antibody cocktail, total revenues grew 18% versus the prior year.

第三季度，總營收年增51%至35億美元。攤薄後每股淨收益年增84%至15.37美元，淨利為18億美元。若不計入新冠病毒抗體雞尾酒療法的相關收入，總營收較上年同期成長18%。

Starting with REGEN-COV. In the third quarter, we recognized $677 million of U.S. net sales, which consist largely of the initial deliveries of approximately 300,000 doses to the U.S. government under the new 1.4 million dose contract as announced in September. Our collaborator, Roche, record sales of the COVID-19 antibody cocktail known as Ronapreve outside the U.S. In accordance with our Roche agreement, as a true-up payment for global profits, we recorded an additional $127 million as Roche collaboration revenue.

首先來看 REGEN-COV。第三季度，我們確認了 6.77 億美元的美國淨銷售額，這主要包括根據 9 月宣布的 140 萬劑新合同，向美國政府交付的首批約 30 萬劑疫苗。我們的合作夥伴羅氏公司在美國以外地區創下了新冠病毒抗體雞尾酒療法 Ronapreve 的銷售紀錄。根據我們與羅氏公司的協議，作為全球利潤的調整付款，我們額外確認了 1.27 億美元的羅氏合作收入。

In the fourth quarter, we expect to deliver approximately 800,000 doses of REGEN-COV in the U.S. out of which, Roche will supply approximately half of these doses. We will record all REGEN-COV U.S. net product sales. Given the mix of manufactured product supply to the market by Roche and Regeneron, the true-up payment for global profits is expected to result in 0 Roche collaboration revenues in the fourth quarter. The remaining doses from the U.S. government contract are expected to be delivered in the first quarter of 2022.

預計第四季我們將向美國交付約80萬劑REGEN-COV疫苗，其中羅氏將供應約一半。我們將記錄所有REGEN-COV疫苗在美國的淨銷售額。鑑於羅氏和Regeneron兩家公司向市場供應的疫苗種類，預計第四季度羅氏合作收入將為零。美國政府合約下的剩餘疫苗預計將於2022年第一季交付。

I will now move to our Bayer collaboration. Ex-U.S. EYLEA net product sales reported to us by Bayer worth $931 million for the third quarter of 2021, representing growth of 19% on a reported basis and 18% on a constant currency basis. Total Bayer collaboration revenue was $365 million, of which we recorded $351 million for our share of net profits from EYLEA sales outside the U.S.

接下來我將談談我們與拜耳的合作。拜耳向我們報告稱，2021年第三季度，除美國以外，EYLEA產品的淨銷售額為9.31億美元，按報告匯率計算增長19%，按固定匯率計算增長18%。拜耳合作的總收入為3.65億美元，其中我們計入了來自美國以外EYLEA銷售的3.51億美元淨利份額。

Total Sanofi collaboration revenue was $582 million in the third quarter of 2021. Our share of the profits from the commercialization of Dupixent and Kevzara was $387 million, which compares favorably to our share of profits of $213 million in the prior year. We also recognized a $50 million sales milestone payment related to achievement of $1.5 billion of ex-U.S. sales for the collaboration on a rolling 12-month basis.

2021年第三季度，賽諾菲合作項目的總收入為5.82億美元。我們從Dupixent和Kevzara的商業化中獲得的利潤份額為3.87億美元，較上年同期的2.13億美元有所增長。此外，我們還確認了一筆5000萬美元的銷售里程碑付款，該付款與合作項目在過去12個月內美國以外地區的銷售額達到15億美元有關。

Moving on to operating expenses. R&D decreased slightly to $592 million, primarily due to lower spending of REGEN-COV development as compared to the third quarter of 2020.

接下來是營運費用。研發費用略微下降至 5.92 億美元，主要是因為與 2020 年第三季相比，REGEN-COV 的研發支出減少。

Next, SG&A expense increased 34% year-over-year to $391 million, primarily due to costs related to growth initiatives for EYLEA and higher headcount. Cost to goods sold increased versus the prior year from $122 million to $224 million, primarily due to REGEN-COV manufacturing costs. Cost of collaboration manufacturing increased 50% year-over-year to $214 million, driven by higher production to support the growing Dupixent sales. Finally, the effective tax rate was 10.8% in the third quarter of 2021.

其次，銷售、一般及行政費用年增34%至3.91億美元，主要原因是安永（EYLEA）成長計畫的相關成本以及員工人數增加。銷售成本較上年同期從1.22億美元增加至2.24億美元，主要原因是REGEN-COV的生產成本增加。合作生產成本年增50%至2.14億美元，主要原因是為支持Dupixent銷售成長而提高了產量。最後，2021年第三季的實際稅率為10.8%。

Shifting to cash flow on the balance sheet. Year-to-date, Regeneron has generated $4.3 billion in free cash flow and ended the quarter with cash and marketable securities less debt of $8.7 billion. We continued to utilize our strong balance sheet in accordance with our capital allocation priorities of investing in internal R&D, funding strategic external R&D partnerships and returning cash to shareholders. Accordingly, in the third quarter, we repurchased approximately $191 million of our shares.

資產負債表上的現金流量情況有所調整。今年迄今，Regeneron已產生43億美元的自由現金流，截至本季末，公司現金及有價證券減去債務後餘額為87億美元。我們繼續利用穩健的資產負債表，按照既定的資本配置優先事項進行投資，包括投資內部研發、為策略性外部研發合作提供資金以及向股東返還現金。因此，在第三季度，我們回購了約1.91億美元的股票。

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.

最後，我想就我們2021年的業績指引做一些更新。完整的全年業績指引摘要已發佈在我們今天早些時候發布的新聞稿中。

With our -- we are updating our 2021 gross margin guidance to be approximately 88%. This estimate is inclusive of an expected payment to Roche as a true-up of global profits for the COVID-19 antibody cocktail, which will be reported as cost of goods sold. As a result, we expect our gross margin percentage in the fourth quarter to be the lowest of the year.

有鑑於此，我們將2021年毛利率預期更新至約88%。這項預期已包含預計支付給羅氏公司的一筆款項，該款項是對羅氏公司新冠病毒抗體雞尾酒療法全球利潤的調整，並將計入銷售成本。因此，我們預計第四季的毛利率將是全年最低的。

We are also updating our 2021 R&D guidance to be in the range of $2.55 billion to $2.6 billion. The change to the guidance range is related to updated phasing of expenses and lower spend on REGEN-COV. Looking ahead, we will continue to make investments into both our commercial business and our broad pipeline for long-term growth. In particular, we expect to advance critically important development programs in 2022, including the late-stage studies for the LAG-3 Libtayo combo, BCMA by CD3 and C5 along with branded comparators, as George mentioned earlier, in advancing programs with our collaborators.

我們同時更新了2021年的研發預算預期，調整為25.5億美元至26億美元。預算預期的調整與費用分期安排的更新以及REGEN-COV項目支出的減少有關。展望未來，我們將繼續投資於商業業務和廣泛的產品線，以實現長期成長。特別是，我們預計將在2022年推進一些至關重要的研發項目，包括LAG-3 Libtayo聯合療法、BCMA by CD3和C5療法以及品牌對照藥物的後期研究。正如George之前提到的，我們將與合作夥伴共同推動這些計畫。

In conclusion, we're pleased with the third quarter as we invest in our robust pipeline to drive sustained long-term growth. I will now turn the call back to Justin.

總而言之，我們對第三季的業績感到滿意，因為我們將繼續投資於我們強大的產品線，以推動長期持續成長。現在我將把電話會議交還給賈斯汀。

Thank you, Bob. Didi, that concludes our prepared remarks. We'd now like to open the call for Q&A.

謝謝鮑勃。迪迪，我們的演講稿到此結束。現在進入問答環節。

(Operator Instructions) Please go ahead, Didi.

（操作員指示）請開始，滴滴。

(Operator Instructions) Our first question comes from Geoff Porges of SVB Leerink.

（操作說明）我們的第一個問題來自 SVB Leerink 的 Geoff Porges。

Congratulations on the really remarkable results and the outlook. George, perhaps I could ask you about the costims. We've been wondering when we're going to see the first data for the CD28 costims. Could you clarify exactly what we should expect to see next year? And from which combinations? And then just related to that, just these coming up, and there's a lot of discussion about 4-1BB. Could you clarify why you chose to pursue CD28 for your costims rather than 4-1BB?

祝賀你們取得如此卓越的成果和令人振奮的前景。喬治，或許我可以問你一些關於聯合模擬的問題。我們一直想知道什麼時候能看到CD28聯合模擬的第一批數據。能否具體說明我們明年應該期待看到什麼？以及哪些組合的數據？另外，還有一點，目前有很多關於4-1BB的討論。你能否解釋為什麼你們選擇CD28而不是4-1BB來進行聯合模擬？

Yes. As we indicated, we'll be hopefully providing data in the coming year, and it all depends on how the trials progress. Obviously, one has to deal with combination trials where one is dose escalating. And so those are what are limiting getting to effective doses and so forth. In terms of the choices, it all dependent on the science. Our various studies preclinically and in humanized animal models, which show that it was, in our minds, it made most sense to initiate our efforts with the CD28 costim approach.

是的。正如我們之前提到的，我們希望明年能夠提供相關數據，但這完全取決於試驗的進展。顯然，我們必須處理合併用藥試驗中劑量遞增的問題。因此，這些因素限制了我們獲得有效劑量等等。至於選擇方案，一切都取決於科學根據。我們進行的各項臨床前研究以及在人源化動物模型中的研究表明，我們認為，首先採用CD28共刺激策略是最合理的。

Our next question comes from Chris Raymond of Piper Sandler.

我們的下一個問題來自Piper Sandler公司的Chris Raymond。

I guess maybe more of a macro question. I know the ink is hardly even dry, I guess, on some of the prescription drug pricing framework negotiations and the write-up that's a company that from Congress. But this is something I'm sure you guys are watching closely. And obviously, any changes to Medicare Part B is potentially impactful to your business. Just any thoughts here on the impact to EYLEA, especially when considering the cap on out-of-pocket spending that's been proposed and discussed?

我想這或許是一個更宏觀的問題。我知道處方藥定價框架談判和國會提交的文件墨跡可能還未乾。但我相信你們都在密切關注此事。顯然，任何對聯邦醫療保險B部分的改變都可能對你們的業務產生影響。你們對EYLEA可能受到的影響有什麼看法？特別是考慮到已經提出並討論過的自付費用上限？

So Chris, you're right. The ink isn't dry. Some of the bill has been written in disappearing ink and some is in changing ink, but -- so it's hard to get a fix on it. I would say -- as I understand the bill and based on the most recent update, the cap on expenditures is limited to Part D, as in David, drugs. So it would not affect Part B, as in boy. I think I've got that right as I said -- as you said, the ink is really not dry.

克里斯，你說得對。墨跡還沒乾。法案的部分內容是用消失墨水寫的，部分內容是用會變色的墨水寫的，所以很難確定具體內容。我想說的是——根據我對法案的理解以及最新的更新，支出上限僅限於D部分，也就是大衛的藥物部分。所以它不會影響B部分，也就是男孩的部分。我想我的理解沒錯，就像我說的——正如你所說，墨跡確實還沒乾。

I will say that, generally speaking, it is quite remarkable just from my personal perspective, that the industry that is most responsible for getting the country in the world out of the pandemic in as best shape as we can is the source of such great attack. But fortunately, I think that some rational heads have prevailed and the most draconian ideas have been written in that disappearing ink.

總的來說，就我個人而言，最令人驚訝的是，對國家乃至全世界盡可能擺脫疫情負有最大責任的行業，竟然成瞭如此猛烈攻擊的源頭。但幸運的是，我認為一些理性的人最終佔了上風，那些最嚴苛的想法也隨著時間的流逝而被扼殺了。

Our next question comes from Yaron Werber of Cowen and Company.

我們的下一個問題來自 Cowen and Company 的 Yaron Werber。

Congrats on the team on a great quarter. Really just a quick one actually on the pozelimab and cemdisiran combo. I'd already mentioned some potential combo treatment studies, PNH and MG. Again, some of the other C5s, really kind of wanted to ask a little bit about how you're thinking about real-world use of this one. I know there's a lot of movement in -- especially the MG space. Is this something that we should expect to compete maybe more with Soliris? Or are you thinking a little bit further up the line against IVIG or some of the FcRns? Just kind of want to get your thoughts there.

恭喜團隊本季表現出色。其實我只是想簡單問一下關於pozelimab和cemdisiran聯合療法的問題。我之前已經提到過一些潛在的聯合治療研究，像是PNH和MG。另外，還有一些其他的C5藥物，我想問你們是如何看待這種聯合療法在實際應用上的。我知道目前有很多進展，尤其是在MG領域。這種療法是否會與Soliris展開更激烈的競爭？還是你們認為它比較適合與靜脈注射免疫球蛋白（IVIG）或一些FcR受體拮抗劑競爭？我只是想聽聽你們的看法。

Yes. I mean we are hoping that this is going to turn out to be the best-in-class in terms of efficacy and also in terms of convenience for these disease categories. So yes, we're thinking about and depending on how the landscape evolves, that, that could be the opportunity that we would be going after.

是的。我的意思是，我們希望這款產品在療效和便利性方面都能成為同類產品中的最佳選擇，尤其針對這些疾病類別。所以，是的，我們正在考慮，而且根據市場格局的發展，這或許就是我們要抓住的機會。

Our next question comes from Josh Schimmer of Evercore ISI.

我們的下一個問題來自 Evercore ISI 的 Josh Schimmer。

For the high-dose aflibercept Phase III studies, what signals are you looking for a potential filing as [OCD sickness] benefit alone insufficient to move forward. Is that going to be under a new BLA or an SBLA? And as such, how do you think that would fall under proposed drug pricing legislation and whether it would reset the clock for that product?

對於高劑量阿柏西普的III期研究，您會注意哪些訊號來判斷是否僅憑強迫症疾病福利不足以推進該藥物的上市申請？該申請會以新的生物製品許可申請（BLA）還是補充生物製品許可申請（SBLA）的形式提交？如果是這樣，您認為這會如何與擬議的藥品定價立法相衝突，以及這是否會重置該產品的上市時間？

Yes. I'll comment on the regulatory assets and George can comment maybe on the design aspects. But at the moment, we don't think this would be a new BLA, and this would be part of the -- this would likely be an SBLA, George?

是的。我會就監管方面發表意見，喬治可以就設計方面發表意見。但目前，我們認為這不會是一份新的生物製品許可申請（BLA），而很可能是一份小型企業許可申請（SBLA），喬治？

Yes. Basically, we are, as you said, we're looking, of course, to look at differences in terms of anatomic improvements, but the trial is a noninferiority study. Where we're going to be testing is whether patients that are being treated at a dramatically increased interval do as well as regular dose EYLEA had an 8-week interval. So it's going to depend on hopefully seeing that substantially higher numbers of patients are going to be able to be treated at extended dose intervals compared to the 2-milligram dose while achieving similar visual acuity effects.

是的。正如您所說，我們當然會關註解剖結構改善的差異，但這項試驗是一項非劣效性研究。我們將要檢驗的是，接受治療間隔顯著延長的患者，其療效是否與接受常規劑量EYLEA治療（間隔8週）的患者一樣好。因此，我們希望看到，與2毫克劑量相比，更多患者能夠在延長給藥間隔的情況下獲得相似的視力改善效果。

Our next question comes from Carter Gould of Barclays.

下一個問題來自巴克萊銀行的卡特·古爾德。

Excellent results, guys. I wanted to ask on REGN14256, I guess, the new running partner for imdevimab. And if development was really in response to a specific shift you're seeing in the variants or lower efficacy? Or if you were looking to optimize on other domains? And I guess, in responding to that, could you also address kind of your expectations for running studies, conducting studies with a, I guess, a lower background rate of hospitalization?

各位，結果非常棒！我想問關於REGN14256的問題，它應該是imdevimab的新夥伴。它的研發是否真的是為了因應你們觀察到的特定變異或療效下降？還是說你們希望優化其他方面？另外，能否也談談你們對進行研究的預期，特別是考慮到住院率較低的情況？

Yes, all good and somewhat complicated questions. Right now, obviously, as we've said, our cocktail remains active against all the known variants of concern that have emerged and created issues for other antibodies and so forth. However, we want to be prepared. So we're creating a complementary cocktail that if ever variants would arise that would raise problems for our current cocktail, we would have a complementary cocktail that the way we designed it would hopefully be unaffected by the same types of mutations. So it's to be prepared for that possibility that as the virus continues to evolve, we might need a cocktail that might not be sensitive to the same mutations as the first cocktail. But the current cocktail is still active against the variants of concern.

是的，這些都是很好且有些複雜的問題。目前，正如我們所說，我們的混合療法仍然有效，可以對抗所有已知的、對其他抗體等構成威脅的變異株。但是，我們希望做好準備。因此，我們正在研發一種補充混合療法。如果未來出現可能對現有混合療法造成影響的變異株，我們就能使用這種補充療法。根據我們的設計，這種補充療法有望不受相同類型突變的影響。我們這樣做是為了應對病毒不斷進化，可能需要一種對現有混合療法中相同突變不敏感的療法。但目前的混合療法仍然有效，可以對抗所有威脅性的變異株。

Yes. There's a lot of questions in terms of how to design the study, where to do it, depending on rates of hospitalization and rates of infection. So these are the complications that we've had to navigate throughout this pandemic, as you might remember. And throughout this pandemic, we have managed to carry out the largest COVID-19 program for treatment and for prevention using antibodies. And we hope that, that all the knowledge that we gained from learning how to navigate changing, fluctuating infection rates and hospitalization rates and so forth, we can continue to take advantage of that and continue to carry out our program efficiently and as quickly as possible.

是的。關於如何設計這項研究，在哪裡進行研究，都存在著許多問題，這取決於住院率和感染率。正如您可能記得的，這些都是我們在整個疫情期間不得不應對的複雜情況。在整個疫情期間，我們成功地開展了規模最大的新冠病毒治療和預防項目，該項目利用抗體進行治療和預防。我們希望，從應對不斷變化的感染率和住院率等方面所獲得的知識，能夠繼續發揮作用，並儘可能高效、迅速地推進我們的計畫。

Yes. Let me just add to that and emphasize what George has said in his earlier remarks, which is that a lot of what we see as the big future need is in the pre-exposure prophylaxis. And that pre-exposure prophylaxis is likely not to go away because of the ongoing infections, the breakthrough infections that still occur in fully vaccinated people. Mind you, with the orals coming, we'll see whether they actually get to the United States. They do have some safety and efficacy issues as a class so far. They have not demonstrated the comparable core study comparisons, notwithstanding the kind of efficacy that monoclonals have delivered nor have they satisfied so many people's satisfaction, the safety concerns around using ImmunoGen perhaps okay for short term.

是的。我只想補充一點，強調喬治之前提到的，我們認為未來最大的需求是暴露前預防。由於持續存在的感染，以及在完全接種疫苗的人群中仍然會出現突破性感染，因此暴露前預防不太可能消失。請注意，口服疫苗即將上市，我們拭目以待它們能否真正進入美國市場。就目前而言，口服疫苗作為一個類別確實存在一些安全性和有效性問題。儘管單株抗體疫苗展現了相當的療效，口服疫苗尚未在核心研究中展現出可比性，也未能讓許多人滿意。使用ImmunoGen疫苗的安全性問題或許短期內尚可接受。

But when you're getting into longer-term prophylaxis of the immunocompromised, which is where George mentioned, we have a lot of work ongoing. It's really important to remember that we expect to have -- our molecules should be able to be given quite less frequently, I think, one might expect because you're looking at a prophylaxis mode. And we think that they should, based on the evidence we have, delivered really rather remarkable efficacy in that setting as they already have in the non-immunocompromised. So as the market transitions to a prophylaxis mode, we see an ongoing demand and need, which we're preparing to meet for monoclonal cocktail therapy.

但說到免疫功能低下人群的長期預防，正如喬治所提到的，我們還有很多工作要做。需要特別注意的是，我們預期我們的分子藥物給藥頻率會大大降低，因為這是預防性的治療方案。根據我們所掌握的證據，我們認為它們在預防性治療中也應該像在非免疫功能低下人群中一樣，在預防性治療中展現出非常顯著的療效。因此，隨著市場向預防性治療模式轉型，我們看到了持續的需求，而我們正在積極準備，以滿足單株抗體雞尾酒療法的需求。

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

下一個問題來自加拿大皇家銀行資本市場的 Kennen MacKay。

First, let me say to Len that I got your commentary towards political or rather governmental purchases of the REGEN-COV antibody cocktail. Thank you for being the voice of science and reason here. Maybe for my question, I have actually really admired your BD strategy, which shows a lot of awareness recognizing areas of expertise, but also limitations and looking to be in partnerships and licensing to outsource the latter. I was wondering what you're really interested now on the BD front, if there are any technologies that are jumping out as additional areas of opportunity for the company?

首先，我想對Len說，我理解你對政府或政治機構採購REGEN-COV抗體雞尾酒療法的評論。感謝你在這裡代表科學和理性發聲。至於我的問題，我其實非常欣賞你的業務拓展策略，它展現了你對自身專業領域的深刻理解，同時也意識到自身的局限性，並尋求透過合作和授權的方式將後者外包出去。我想知道你現在在業務拓展方面真正感興趣的是什麼？是否有任何科技領域脫穎而出，成為公司新的發展機會？

And then sort of partial to that, whether you are at all interested in this newly emerging field of protein degradation and protein degraders, as Oncology targets?

那麼，我個人比較傾向於這個領域，您是否對蛋白質降解和蛋白質降解劑作為腫瘤治療標靶這一新興領域感興趣？

George should take this. He's been the architect of the scientific underpinnings of our BD strategy and having a remarkable vision to be able to integrate that with our core expertise, George?

喬治應該接手這個職位。他是我們業務拓展策略科學基礎的奠基人，而且他擁有卓越的遠見，能夠將這些科學基礎與我們的核心專長相結合，喬治，對嗎？

Well, yes, I think if we were looking to get into new technologies and have new relationships, I don't think we would be telling you about them at this time.

嗯，是的，我想如果我們想要涉足新技術和建立新的合作關係，目前我們不會告訴你們這些。

Wait, George. Could you comment on your prior strategy on how siRNA and (inaudible)?

等等，喬治。可以談談你之前關於siRNA和（聽不清楚）的策略嗎？

Well, I think, yes, what Len referring to is I think that the whole team, the whole company at many levels from the business development group through -- the science research folks through our premanufacturing group has done a spectacular job of pivoting us from a solely biologics company to a genetic medicines company. What we've managed to do is starting with our Regeneron Genetics Center is create what we believe is perhaps the world's most powerful technology to identify new genetic targets based on our sequencing of almost 2 million individuals, all linked to electronic digital records.

嗯，我想，Len 指的正是整個團隊，從業務拓展團隊到科研人員，再到我們的預生產團隊，公司各個層級的人員都出色地完成了轉型，使我們從一家純粹的生物製劑公司轉型為一家基因藥物公司。我們以 Regeneron 基因中心為起點，成功地打造了我們認為可能是世界上最強大的技術，能夠基於近 200 萬人的基因定序數據（所有數據均與電子病歷關聯）來識別新的基因標靶。

That allows us to understand, we think, more powerfully than anybody else, the role of genetic variation, both in disease protection and causation, which have led to a whole series of new disease targets for both protection and causation. And for those, some of those are addressable by biologics and they're part of our existing approaches with biologics, but we had to use new approaches. And for those purposes, we started creating some of these important outside alliances and collaborations with companies like Alnylam for the siRNA approaches, we talked a little bit about and with Intellia with CRISPR-based approaches.

這使我們能夠比任何人都更深刻地理解基因變異在疾病保護和致病中的作用，從而發現了一系列新的疾病靶點，這些靶點既可用於疾病保護，也可用於致病治療。其中一些標靶可以透過生物製劑進行治療，並且是我們現有生物製劑治療方案的一部分，但我們必須採用新的方法。為此，我們開始與一些重要的外部公司建立聯盟和合作，例如與Alnylam公司合作開發siRNA技術，以及與Intellia公司合作開發基於CRISPR的技術。

Many of these, we've been able to build and create and take them to another level based on our very productive collaborations with these 2 great companies that we're now collaborating with. And we also invested enormously internally in terms of building our own gene therapy approaches. So we believe that we're positioning ourselves to become leaders for the foreseeable future over the next decade or so in the genetic medicine space. It's becoming an increasingly important and larger part of our portfolio. It's almost a whole separate company, we believe, in terms of the opportunities and the value that it generates. While we're maintaining our leadership position with biologics, not only with classical antibodies but also with bispecifics and all sorts of engineered formats of biologics. So I think it's been a tremendous job by our entire team and organization to essentially create this entirely new capability.

我們與這兩家優秀的公司進行了卓有成效的合作，在此基礎上，我們得以建構、創造並提升了許多技術，使其更上一層樓。同時，我們也投入大量資金自主研發基因療法。因此，我們相信，在未來十年左右的時間裡，我們已做好準備，成為基因藥物領域的領導者。基因藥物在我們產品組合中佔據越來越重要的地位。我們認為，就其帶來的機會和價值而言，它幾乎可以算作一家獨立的公司。同時，我們在生物製劑領域也保持領先地位，不僅包括傳統抗體，還包括雙特異性抗體以及各種工程化生物製劑。我認為，我們整個團隊和組織為打造這項全新能力做出了卓越的貢獻。

Our next question comes from Ronny Gal of Alliance Bernstein.

我們的下一個問題來自 Alliance Bernstein 的 Ronny Gal。

So following on the last question, can you comment a little bit about when we can see your first kind of CRISPR-based technology in a trial that you run coming into the clinic? Will it be in 2022 or 2023? And then with this full additional company, should we expect the R&D cost to continue to rise roughly at the rate they've historically been?

接著一個問題，您能否簡單介紹一下您進行的首個基於 CRISPR 技術的臨床試驗何時啟動？是在 2022 年還是 2023 年？另外，隨著公司規模的擴大，研發成本是否會繼續以過去的速度成長？

Okay. I'll remind you that I believe we announced last quarter, our first CRISPR results which were the first obtained by anybody in history in terms of using a systemic CRISPR-based therapy to actually modify genes within human beings. It was an incredibly successful study that we did in collaboration with Intellia. It was the first-ever systemic investigational CRISPR-based gene knockout approach. And in the first set of patients that we treated, we show that a single dose of this CRISPR-based therapy led to very dramatic and dose-dependent reductions in the target protein coming from the target gene. I think that the world viewed this as incredibly exciting data.

好的。我提醒各位，我們在上個季度公佈了首個CRISPR研究成果，這是史上首次利用全身性CRISPR療法對人體內基因進行修飾。這項與Intellia合作進行的研究非常成功，也是首個全身性CRISPR基因敲除研究。在首批接受治療的患者中，我們發現單次CRISPR療法即可顯著降低目標基因表現的標靶蛋白水平，且降低幅度呈劑量依賴性。我認為，全世界都對這些數據感到無比振奮。

I believe we announced it in June of '21. And I think it's just the beginning of a very large program. We have about 20 preclinical programs now under evaluation that will be rolling out in terms of going into the clinic and producing clinical results over the next couple of years.

我相信我們是在2021年6月宣布的。我認為這只是一個龐大計劃的開始。我們目前正在評估大約20個臨床前項目，這些項目將在未來幾年內陸續進入臨床試驗階段並產生臨床結果。

And Ronny, let me punctuate, right? So we'll give kind of guidance in our fourth quarter earnings in early February. I will tell you, if you look at our kind of run rate this year, R&D relative to 2020, we're coming out at roughly a 7% increase if you take the midpoint of my guidance. And I guess my word of caution is a lot of that's heavy REGEN-COV in 2020. So we're going up against the big REGEN-COV number in 2020 as compared to what we incurred in 2021. So that 7% is, I'd say, artificially light compared to where we're going to eventually end up and we do give that guidance. So I just want to make sure people are not kind of doing same year run rates as they're seeing in 2021.

羅尼，讓我補充一下，好嗎？我們會在二月初的第四季財報中給予業績指引。我想說的是，如果你看我們今年的研發投入運行速度，以及與2020年相比的成長，如果你取我指引的中位數，大約是7%。但我要提醒大家的是，這其中很大一部分是2020年龐大的再生經濟影響。也就是說，我們2020年要應對的再生經濟影響遠高於2021年。所以，我認為7%的成長率相對於我們最終的實際水準來說偏低，而我們確實給了這樣的指引。我只是想提醒大家，不要把2021年的運行速度和2021年的情況混為一談。

Our next question comes from Matthew Harrison of Morgan Stanley.

下一個問題來自摩根士丹利的馬修·哈里森。

This is [Charlie] on for Matthew. Can you please comment on the Libtayo activities and the commercial dynamics, given the relatively modest kind of quarter-to-quarter growth?

這裡是查理，替馬修提問。鑑於Libtayo的季度環比成長相對溫和，您能否談談Libtayo的營運活動和商業動態？

Sure, [Charlie]. This is Marion. Let me take that. First off, we have great ambition, of course, for Libtayo. As I mentioned, the bulk of our sales today are from our launch of cutaneous squamous cell carcinoma. Understandably, our more recent launches have brought us again into derm with basal cell carcinoma, where Libtayo is very quickly becoming the standard of care for appropriate patients based on its clinical profile and based on, obviously, patients unfortunately fail with hedgehog inhibitors, which also can be really difficult to tolerate. So we're very pleased with how that launch is going early days.

當然，查理。我是瑪莉安，讓我來接。首先，我們對Libtayo寄予厚望。正如我剛才提到的，我們目前的銷售主要來自皮膚鱗狀細胞癌的上市。可以理解的是，我們最近推出的產品又將我們帶回了基底細胞癌的治療領域，Libtayo憑藉其臨床優勢，正迅速成為適合患者的標準治療方案。當然，患者對Hedgehog抑制劑的反應往往不佳，而且Hedgehog抑制劑的耐受性也較差。因此，我們對Libtayo上市初期的進展非常滿意。

Most important, however, is our lung launch. The initial launch we had in monotherapy is understandably for a smaller target group of patients. We do believe, however, though, the experience that physicians are gaining with Libtayo in first-line monotherapy treatment is very, very important and bodes well for when we hopefully have the larger indication approved for chemo combo. And that as many of you are aware is a much larger population of patients, perhaps 4- to 5-fold more patients, and we certainly look forward to potentially being able to launch that larger indication in lung.

然而，最重要的是我們針對肺癌的上市。我們最初推出的單藥療法針對的是較小規模的患者群體，這可以理解。但我們相信，醫生們在利妥昔單抗一線單藥治療中累積的經驗非常寶貴，這為我們日後有望獲準的化療聯合療法奠定了良好的基礎。如大家所知，化療聯合療法的患者群體大得多，可能是單藥療法的4到5倍，我們非常期待能夠盡快推出利妥昔單抗的肺癌適應症。

Our next question comes from Robyn Karnauskas of Truist.

我們的下一個問題來自 Truist 的 Robyn Karnauskas。

I was wondering if you can satisfy a little bit of my curiosity about the news flow coming out of your Intellia partnership. I guess the first question I'd ask is in the event that they'll be hosting next year, in the first quarter, how much durability data might we get for TTR? And then, George, you mentioned the additional indication over the next few years that you'll be going into. When are we going to be hearing about those, would we hear about a lot of them in the beginning of the year or would we hear about them over the course of the year, I know Intellia is of huge investor interest as well as mine.

我想請您解答一下關於您與Intellia合作專案的一些問題。首先，如果他們明年第一季舉辦活動，我們能從TTR獲得多少耐久性數據？其次，George，您提到未來幾年還會有其他項目。我們什麼時候能聽到這些消息？年初會公佈很多，還是會貫穿全年？我知道Intellia專案非常受投資人關注，我也是。

I wonder if we shouldn't give Intellia the opportunity to give that kind of guidance, Robyn.

羅賓，我想知道我們是否應該給 Intellia 一個機會來提供這種指導。

I'm sure that might be the approach.

我相信這很可能是可行的方法。

Our next question comes from Alethia Young of Cantor.

我們的下一個問題來自坎托爾的阿萊西亞·楊。

Before you get with that question. I do think just to help Robyn out a little bit, I think one really important point is, yes, as the data continues to mature and certainly, we expect excellent duration data coming out over time and so forth. But I think we all have to recognize that this represents the first true validation of this entire field and approach. And our ability working with Intellia using our specific approach to actually turn it from dream into reality. And this obviously dramatically increases the probability of success of all of our future programs based on our collaborative technology with Intellia, including both knockout and insertion approaches, and we have to, of course, highlight and point out the lack of such proof of concept and success with any other approaches to date. And I think that, that really distinguishes our collaboration with Intellia. And obviously, should adjust the risk profile for all of our programs going forward, which, as Len said, hopefully, we and Intellia will be giving more resolution on going forward.

在你提出這個問題之前，我想先幫Robyn理清思路。我認為一個非常重要的觀點是，隨著數據的不斷完善，我們當然期待未來能獲得更優異的持續時間數據等等。但我認為我們都必須認識到，這代表著整個領域和方法的首次真正驗證。我們與Intellia合作，運用我們獨特的方法，將夢想變成現實。這顯然大大提高了我們未來所有基於與Intellia合作技術的專案的成功機率，包括基因敲除和基因插入方法。當然，我們必須強調，迄今為止，其他任何方法都缺乏這樣的概念驗證和成功案例。我認為，這正是我們與Intellia合作的獨特之處。顯然，這應該會調整我們未來所有專案的風險評估，正如Len所說，希望我們和Intellia能夠就此提供更多解決方案。

Go ahead, Alethia.

請繼續，阿萊西亞。

Congrats on the quarter. I just had a question about kind of, obviously, you have very robust AOE data with Dupixent. Can you just talk a little bit about how you think about the market opportunity there? And like how -- what diagnosis is like there and how you can potentially expand that?

恭喜你本季業績出色。我有個問題，顯然你們在Dupixent方面擁有非常可靠的AOE數據。能否請你談談你如何看待這個市場的機會？例如，目前的診斷情況如何？你們又該如何拓展這個市場？

Sure. So we're very excited about the possibility of launching Dupixent also for eosinophilic esophagitis. As George was describing, there's tremendous unmet need in the marketplace in patients who truly are suffering and often end up in the emergency room with difficult procedures to try to remedy for the short-term, some of the difficult symptoms they have. The size of patient population for those who are undergoing recurrent treatment is about 48,000. And then obviously, there are patients who are entering the system beyond that. But probably just as a starter number that 48,000 to 50,000 who have failed multiple treatments is the core group. And then we will extend beyond that to probably about another 150,000 patients with EoE, who also have earned the need of treatment. But the failure group, obviously, of 50,000 is the most severe.

當然。我們非常興奮地宣布，Dupixent有望也用於治療嗜酸性粒細胞性食道炎。正如喬治所說，市場上存在著巨大的未滿足需求，許多患者正遭受痛苦，最終不得不前往急診室接受複雜的治療，以期短期緩解一些難以忍受的症狀。接受反覆治療的患者族群規模約為48,000人。顯然，有更多患者正在加入治療系統。但作為初步估算，48,000至50,000名多次治療失敗的患者構成了核心群體。之後，我們將把治療範圍擴大到另外約15萬名同樣需要治療的嗜酸性粒細胞性食道炎患者。但顯然，這50,000名治療失敗的患者群最為嚴重。

Didi, we have time for 2 more quick questions.

迪迪，我們還有時間再問兩個問題。

Our next question is from Esther Rajavelu of UBS.

我們的下一個問題來自瑞銀集團的艾絲特·拉賈韋盧。

I have one on EYLEA, perhaps a multipart question. Can you give us some details on use among diabetics versus nondiabetic patients? And is the uptake among diabetics type to more consistent use among treated patients? Or are you onboarding new diabetics? And lastly, anything you can share on NPDR versus diabetic macular edema patients would be helpful as well.

我有一個關於愛立信（EYLEA）的問題，可能涉及多個面向。能否詳細介紹一下糖尿病患者和非糖尿病患者的使用情況？糖尿病患者的使用率是否高於已接受治療的患者？還是您正在招募新的糖尿病患者？最後，如果您能分享一些關於非增殖性糖尿病視網膜病變（NPDR）患者和糖尿病黃斑水腫患者的信息，那就太好了。

Sure. So let me give you a little bit of background and some characterization. Certainly, our indications for diabetic eye disease are the fastest growing in terms of new patients proportionately coming into the treatment paradigm. We also see a growth in the diabetes treatment population for EYLEA opposite, for example, wet AMD. So now our wet AMD treatment is under 60% of the total utilization of EYLEA in the U.S. marketplace.

當然。那麼就讓我先簡單介紹一下背景和特色。就接受治療的新患者病例而言，我們用於治療糖尿病眼疾的適應症成長速度最快。我們也看到，與濕性老年黃斑部病變（AMD）等情況相反，使用EYLEA治療糖尿病眼疾的患者族群也在成長。目前，濕性AMD的治療量佔EYLEA在美國市場總使用量的60%以下。

The specific growth on diabetic eye disease by indication, it's difficult to give you the exact breakdown, but we are very optimistic on even the early efforts we see in market based on our new unbranded direct-to-consumer TV campaign, which is really educating diabetic patients broadly on the importance of having their vision checked, making sure it's part of the regular check-in as patients with diabetes have other areas that they standardly review and make sure of their care. Eye disease has often been neglected with very disastrous situations of vision loss that can't be corrected. So we see that as a really important area and one that will fuel diabetic eye disease treatment broadly. But even today, and before we embarked upon that program, we see it as a high growth indication.

糖尿病眼疾的具體成長難以提供精確細分，但我們對目前市場上的早期進展非常樂觀。這主要得益於我們新推出的面向消費者的電視廣告宣傳活動，該活動旨在廣泛普及糖尿病患者對視力檢查重要性的認識，確保將其納入常規體檢項目，就像糖尿病患者需要定期檢查其他健康項目一樣。眼疾常被忽視，導致嚴重的視力喪失，而且無法治癒。因此，我們認為這是一個非常重要的領域，它將推動糖尿病眼疾治療的蓬勃發展。即使在我們啟動這個計畫之前，我們也認為糖尿病眼疾是一個高成長的適應症。

Didi, we have time for 1 more question.

迪迪，我們還有時間再問一個問題。

Our last question comes from Yatin Suneja of Guggenheim Partners.

最後一個問題來自古根漢合夥公司的亞廷·蘇內賈。

Congrats on the quarter of good performance. Just quickly on the complement efforts. Can you just talk about other CNS or Neurology applications with either the monotherapy or the combination? And then with respect to the siRNA approach, could we take that -- could you take that into the eye and what the long-term vision there is?

恭喜你們本季業績出色。關於補充療法，能否簡單談談該療法在中樞神經系統或神經病學領域的其他應用，無論是單藥治療還是合併治療？另外，關於siRNA療法，能否談談眼科治療及其長期發展願景？

Yes, we're not going to say too much about your first question. But in terms of your second question, absolutely. And so when we establish this relationship with Alnylam in terms of using siRNA, it was actually directed towards 3 separate areas. So really was 3 separate collaborations. The one in the first that we thought that we'd be moving the most rapidly into the clinic and that has turned out to be the case were with liver targets, both sort of more conventional targets like the C5, but also targets that were coming from our own pipeline like the HSD target that we talked about. And that -- those are all moving along forward and we think a very exciting fashion as we've discussed.

是的，關於您的第一個問題，我們不打算過度贅述。但關於您的第二個問題，答案是肯定的。我們與Alnylam建立siRNA合作關係時，實際上是針對三個不同的領域。所以，我們進行了三項獨立的合作。我們認為，第一個合作計畫——肝臟標靶——能夠最快進入臨床階段，而事實也的確如此。這些標靶既包括像C5這樣比較傳統的靶點，也包括我們自主研發的靶點，例如我們之前提到的HSD標靶。正如我們之前討論的，這些項目都在穩步推進，而且進展非常令人振奮。

Another key area that you just opened up, which is still preclinically, but we're hoping to eventually move into the clinic is targeting the eye targets with siRNAs. And that's really a very important area for us, and it was a very important separate part of the entire Alnylam collaboration.

您剛提出的另一個關鍵領域，目前仍處於臨床前階段，但我們希望最終能將其推進到臨床階段，就是利用siRNA標靶眼部疾病。這對我們來說確實是一個非常重要的領域，也是整個Alnylam合作計畫中一個非常重要的獨立組成部分。

And the third really critical foundational part of our collaboration with Alnylam involved using siRNAs to target in the brain. And that's also moving forward in a very exciting fashion, and we'll be talking a lot more about that going forward. So really, it's a 3 sort of pillar program, liver targets, eye targets and CNS targets. We're very excited and moving forward on all of them. And as we had guided early on, the first set of targets, of course, would be in the liver and then we'd be moving into the other 2 areas as rapidly as possible.

我們與Alnylam合作的第三個至關重要的基礎部分是利用siRNA靶向大腦。這方面的進展也令人振奮，我們將在後續工作中對此進行更詳細的闡述。因此，這實際上是一個包含三大支柱的項目：肝臟標靶、眼部標靶和中樞神經系統標靶。我們對所有這些靶點都非常滿意，並且正在積極推進。正如我們早期所規劃的，第一批靶點當然會是肝臟靶點，然後我們會盡快擴展到其他兩個領域。

Great. Thanks, everyone. That will conclude our call. Bob Landry and the IR team will be available today to answer any additional questions you may have. Thanks, everyone, and stay safe. Goodbye.

好的。謝謝大家。我們的通話到此結束。鮑勃·蘭德里和投資者關係團隊今天將隨時解答大家可能提出的任何其他問題。謝謝大家，請注意安全。再見。

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

今天的電話會議到此結束。感謝您的參與，您可以斷開連接了。