雷傑納榮製藥 (REGN) 2022 Q1 法說會逐字稿

Welcome to the Regeneron Pharmaceuticals' First Quarter 2022 Earnings Conference Call. My name is Gigi, and I'll be your operator for today's call. (Operator Instructions) Please note that this conference is being recorded.

歡迎參加 Regeneron Pharmaceuticals 2022 年第一季度收益電話會議。我的名字是 Gigi，我將成為您今天通話的接線員。 （操作員說明）請注意，本次會議正在錄製中。

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

我現在將把電話轉給投資者關係副總裁 Ryan Crowe。你可以開始了。

Thank you, Gigi. Good morning, good afternoon and good evening to everyone listening around the globe. Thank you for your interest in Regeneron and welcome to our first quarter 2022 earnings conference call. An archive of this webcast will be available on our Investor Relations website shortly after the call ends.

謝謝你，吉吉。早上好，下午好，晚上好，全世界的每一個人都在聽。感謝您對 Regeneron 的興趣，並歡迎參加我們的 2022 年第一季度收益電話會議。電話會議結束後不久，我們的投資者關係網站將提供此網絡廣播的存檔。

Joining me today are Dr. Leonard Schleifer, Founder, President and Chief Executive Officer; Dr. George Yancopoulos, Co-Founder, President and Chief Scientific Officer; Marion McCourt, Executive Vice President and Head of Commercial; and Bob Landry, Executive Vice President and Chief Financial Officer. After our prepared remarks, we will open the call for Q&A.

今天加入我的是創始人、總裁兼首席執行官 Leonard Schleifer 博士； George Yancopoulos 博士，聯合創始人、總裁兼首席科學官； Marion McCourt，執行副總裁兼商務主管；和執行副總裁兼首席財務官 Bob Landry。在我們準備好發言後，我們將打開問答電話。

I would also like to remind you that remarks made on this call today include forward-looking statements about Regeneron. Such statements may include, but are not limited to, those related to Regeneron and its products and businesses, financial forecast and guidance, development programs and related anticipated milestones, collaborations, finances, regulatory matters, payer coverage and reimbursement issues, intellectual property, pending litigation and other proceedings and competition. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement.

我還想提醒您，今天在這次電話會議上發表的言論包括關於 Regeneron 的前瞻性陳述。此類聲明可能包括但不限於與再生元及其產品和業務、財務預測和指導、開發計劃和相關的預期里程碑、合作、財務、監管事項、付款人覆蓋和報銷問題、知識產權、待定訴訟和其他訴訟和競爭。每項前瞻性陳述都存在風險和不確定性，可能導致實際結果和事件與該陳述中的預測存在重大差異。

A more complete description of these and other material risks can be found in Regeneron's filings with the United States' Securities and Exchange Commission, including its Form 10-Q for the quarterly period ended March 31, 2022, which was filed with the SEC this morning. Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

有關這些和其他重大風險的更完整描述，請參見 Regeneron 向美國證券交易委員會提交的文件，包括其截至 2022 年 3 月 31 日的季度的 10-Q 表格，該表格於今天上午向美國證券交易委員會提交. Regeneron 不承擔任何義務更新任何前瞻性陳述，無論是由於新信息、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 the reconciliation of those measures to GAAP is available on our financial results press release, which can be accessed on our website.

此外，請注意，GAAP 和非 GAAP 措施將在今天的電話會議中討論。有關我們使用非 GAAP 財務指標的信息以及這些指標與 GAAP 的對賬信息，請參閱我們的財務業績新聞稿，該新聞稿可在我們的網站上訪問。

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

一旦我們的電話結束，Bob Landry 和 IR 團隊將可以回答任何進一步的問題。

This earnings call is neither an offer to purchase nor a solicitation of an offer to sell securities of CheckMate Pharmaceuticals, Inc. In connection with the tender offer for CheckMate stock, Regeneron and Scandinavian Acquisition Sub, Inc. filed with the SEC and tender offer statement on Schedule TO and other tender offer materials, and CheckMate filed a solicitation recommendation statement on Schedule 14D-9 with the SEC. Copies of the documents filed with the SEC by Regeneron and CheckMate are available free of charge on Regeneron's website at investor.regeneron.com or on CheckMate's website at ir.checkmatepharma.com as applicable, or at the SEC's website at www.sec.gov.

本次財報電話會議既不是購買 CheckMate Pharmaceuticals, Inc. 證券的要約，也不是出售要約的要約。關於向 SEC 提交的 CheckMate 股票、Regeneron 和 Scandinavian Acquisition Sub, Inc. 的要約收購和要約收購聲明關於附表 TO 和其他要約收購材料，CheckMate 向美國證券交易委員會提交了附表 14D-9 的招標建議聲明。 Regeneron 和 CheckMate 向 SEC 提交的文件副本可在 Regeneron 的網站investor.regeneron.com 或 CheckMate 的網站 ir.checkmatepharma.com（如適用）或 SEC 的網站 www.sec.gov 免費獲取.

You should review such materials filed with the SEC carefully because they contain or will contain important information about the tender offer for CheckMate stock that holders of CheckMate securities and other investors should consider before making any decision with respect to the tender offer.

您應仔細查看向 SEC 提交的此類材料，因為它們包含或將包含有關 CheckMate 股票要約收購的重要信息，CheckMate 證券持有人和其他投資者在就要約收購做出任何決定之前應考慮這些信息。

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

有了這個，讓我把電話轉給我們的總裁兼首席執行官 Len Schleifer 博士。倫?

Thank you, Ryan. Welcome to your first earnings call. Hope all of our stakeholders will join me in giving you a warm welcome to the Regeneron team. Thanks to everyone joining the call as well.

謝謝你，瑞安。歡迎參加您的第一次收益電話會議。希望我們所有的利益相關者和我一起熱烈歡迎您加入 Regeneron 團隊。也感謝大家加入電話會議。

Following an exceptional 2021, Regeneron is off to a strong start in 2022. Our first quarter results were driven by execution across the entire company as we continue to realize the benefits of our sustained investment in differentiated research and development, along with our focus on commercial performance.

在經歷了非凡的 2021 年之後，再生元 (Regeneron) 在 2022 年迎來了強勁開局。我們第一季度的業績受到整個公司執行力的推動，因為我們繼續意識到我們對差異化研發的持續投資以及我們對商業的關注所帶來的好處表現。

We also continue to drive shareholder value through prudent capital allocation, including approximately $350 million of share repurchases in the first 3 months of this year.

我們還通過審慎的資本配置繼續推動股東價值，包括在今年前 3 個月進行約 3.5 億美元的股票回購。

Regarding our financial performance, we delivered strong double-digit revenue and non-GAAP earnings per share growth. Excluding revenue contributions from our investigation of COVID antibody cocktail, revenues grew 25%, reflecting our increasingly diversified core business, which continues to thrive.

關於我們的財務業績，我們實現了強勁的兩位數收入和非公認會計準則每股收益增長。不包括我們對 COVID 抗體雞尾酒調查的收入貢獻，收入增長了 25%，反映了我們日益多元化的核心業務，該業務繼續蓬勃發展。

For EYLEA, global net sales grew 11% to nearly $2.4 billion in the first quarter, including $1.5 billion of revenues in the United States, up 13% versus last year, which outpaced the U.S. anti-VEGF category growth. In yet another milestone for EYLEA, after more than 10 years, we recently surpassed 50 million EYLEA injections globally, a testament to its well-established efficacy and safety profile.

對於 EYLEA，第一季度全球淨銷售額增長 11% 至近 24 億美元，其中包括美國的 15 億美元收入，比去年增長 13%，超過了美國抗 VEGF 類別的增長。在 EYLEA 的另一個里程碑中，經過 10 多年，我們最近在全球進行了超過 5000 萬次 EYLEA 注射，這證明了其良好的療效和安全性。

We believe EYLEA continues to represent a significant long-term growth opportunity, primarily driven by an aging population, increasing utilization among a rapidly-growing diabetic population as well as the potential for our investigational aflibercept 8 milligrams to complement and enhance our retinal franchise.

我們相信 EYLEA 繼續代表著一個重要的長期增長機會，主要受人口老齡化、快速增長的糖尿病人口使用率增加以及我們的研究性阿柏西普 8 毫克補充和增強我們的視網膜專營權的潛力的推動。

For Dupixent, in quarter 1, global revenues for the quarter exceeded $1.8 billion, an increase of 43% to last year as we continue to redefine the treatment of Type 2 inflammatory diseases. A significant opportunity remains to reach even more patients in already-approved indications, and we look forward to potentially launching Dupixent in 7 new indications in the U.S. later this year and in early 2023, including pediatric atopic dermatitis, eosinophilic esophagitis and prurigo nodularis. Collectively, approximately 200,000 U.S. patients are suffering from these 3 indications today, but currently have no approved -- no FDA-approved systemic treatment options.

對於 Dupixent，在第一季度，隨著我們繼續重新定義 2 型炎症性疾病的治療，該季度的全球收入超過 18 億美元，比去年增長 43%。在已獲批准的適應症中接觸更多患者仍然是一個重要的機會，我們期待在今年晚些時候和 2023 年初在美國推出用於 7 個新適應症的 Dupixent，包括小兒特應性皮炎、嗜酸性粒細胞性食管炎和結節性癢疹。總的來說，今天大約有 200,000 名美國患者患有這 3 種適應症，但目前還沒有獲得批准——沒有 FDA 批准的系統治療方案。

In oncology, Libtayo continues to capture significant share in FDA-approved non-melanoma skin cancer indications where it is considered the standard of care. Beyond dermato-oncology, we're beginning to generate momentum in monotherapy non-small cell lung cancer in the United States, helping to build a foundation for potential launch of Libtayo plus chemotherapy later this year, which would allow Libtayo to address a much larger population of non-small cell lung cancer patients.

在腫瘤學領域，Libtayo 繼續在 FDA 批准的非黑色素瘤皮膚癌適應症中佔據重要份額，並被視為護理標準。除了皮膚腫瘤學，我們開始在美國推動單一療法非小細胞肺癌的發展，幫助為今年晚些時候推出 Libtayo 加化療奠定基礎，這將使 Libtayo 能夠解決更大的問題非小細胞肺癌患者人群。

As we have said before, we continue to consider Libtayo to be foundational to our immuno-oncology development strategy and expect it to serve as the backbone for our investigational clinical program in combination with various antibodies, bispecifics and co-stimulatory bispecifics in our pipeline as well as other pipeline candidates, including those from our collaborations.

正如我們之前所說，我們繼續認為 Libtayo 是我們免疫腫瘤學開發戰略的基礎，並期望它與我們管道中的各種抗體、雙特異性和共刺激雙特異性結合成為我們研究性臨床項目的支柱以及其他管道候選人，包括我們合作的候選人。

In April, we announced our agreement to acquire CheckMate Pharmaceuticals, Regeneron's first-ever acquisition of the company. Upon closing, we expect CheckMate differentiated Toll receptor 9 agonist, vidutolimod, will add a promising new modality to Regeneron's pipeline of potential approaches for difficult-to-treat cancers.

4 月，我們宣布了收購 CheckMate Pharmaceuticals 的協議，這是 Regeneron 對該公司的首次收購。完成後，我們預計 CheckMate 分化的 Toll 受體 9 激動劑 vidutolimod 將為 Regeneron 的難治性癌症潛在方法管線增添一種有前途的新模式。

Looking ahead, we remain on track for the second half of this year to share data in difficult-to-treat solid tumors, such as ovarian and prostate cancers; to submit a BLA for odronextamab, a potentially best-in-class CD20xCD3 bispecific for refractory B-cell lymphomas; and to advance REGN5458, our BCMAxCD3 bispecific.

展望未來，我們將在今年下半年繼續分享難以治療的實體瘤的數據，例如卵巢癌和前列腺癌；提交 odronextamab 的 BLA，這是一種潛在的同類最佳 CD20xCD3 雙特異性難治性 B 細胞淋巴瘤；並推進 REGN5458，我們的 BCMAxCD3 雙特異性。

Finally, regarding our ongoing COVID-19 response, Regeneron remains committed to combating the virus as we head towards the likely endemic stage. We firmly believe that monoclonal antibodies will continue to play an important role, particularly to protect immunocompromised individuals who do not respond adequately to COVID-19 vaccines as well as to treat infected patients whom an oral antiviral therapy is not well tolerated or might trigger serious drug-drug interactions. We are progressing next-generation antibodies that are designed to be active against multiple variants, including those of Omicron lineage, and initiated a first-in-human study last month.

最後，關於我們正在進行的 COVID-19 應對措施，Regeneron 將繼續致力於與病毒作鬥爭，因為我們正邁向可能的流行階段。我們堅信單克隆抗體將繼續發揮重要作用，特別是保護對 COVID-19 疫苗沒有充分反應的免疫功能低下的個體，以及治療口服抗病毒治療不能很好耐受或可能引發嚴重藥物的感染患者-藥物相互作用。我們正在開發下一代抗體，這些抗體旨在對抗多種變體，包括 Omicron 譜系的變體，並於上個月啟動了一項首次人體研究。

Concurrently, as the FDA continues their review of our REGEN-COV BLA for COVID-19 treatment and prophylaxis, we are working closely and collaboratively with them and other global regulatory authorities to establish clinical and regulatory pathways to bring additional safe and effective monoclonal treatment options to patients as quickly as possible.

同時，隨著 FDA 繼續審查我們用於 COVID-19治療和預防的 REGEN-COV BLA，我們正在與他們和其他全球監管機構密切合作，建立臨床和監管途徑，以帶來更多安全有效的單克隆治療選擇盡快給患者。

In closing, we are excited about the strong commercial momentum for our in-line portfolio and the progress we have made advancing our pipeline so far this year. For the remainder of 2022, we anticipate up to 8 additional U.S. and EU regulatory approvals, up to 4 additional U.S. or EU regulatory filings, pivotal data for aflibercept at 8 milligrams as well as various other data readouts from other pipeline programs, which George will discuss.

最後，我們對我們的在線產品組合的強勁商業勢頭以及我們今年迄今為止在推進我們的管道方面取得的進展感到興奮。在 2022 年剩餘時間內，我們預計將獲得多達 8 個額外的美國和歐盟監管批准、多達 4 個額外的美國或歐盟監管文件、8 毫克阿柏西普的關鍵數據以及來自其他管道項目的各種其他數據讀數，喬治將討論。

We remain confident in the long-term outlook for our business, and our pipeline continues to be highly productive, and we are in a strong financial position, all of which positions Regeneron to deliver sustainable growth and long-term value creation.

我們對我們業務的長期前景充滿信心，我們的管道繼續保持高產，我們處於強勁的財務狀況，所有這些都使 Regeneron 能夠實現可持續增長和長期價值創造。

Now, I will turn the call over to George.

現在，我將把電話轉給喬治。

Thank you, Len, and I will start with ophthalmology today.

謝謝你，Len，我今天將從眼科開始。

At the recent Angiogenesis meeting, we presented encouraging results for the Phase II CANDELA study of aflibercept 8 milligram in patients with wet AMD. CANDELA met the primary safety endpoints with no new safety signals observed through week 44, and efficacy endpoints numerically favored aflibercept 8 milligram in visual acuity, drying and other anatomical measures through week 44.

在最近的血管生成會議上，我們為濕性 AMD 患者中阿柏西普 8 毫克的 II 期 CANDELA 研究提出了令人鼓舞的結果。 CANDELA 達到了主要安全終點，在第 44 週沒有觀察到新的安全信號，而療效終點在數值上支持阿柏西普 8 毫克在視力、乾燥和其他解剖學測量中到第 44 週。

Phase III studies, PHOTON in DME and PULSAR in wet AMD are ongoing. The primary objective of the Phase III study is to determine whether aflibercept 8 milligram dosing can allow for more extended dosing intervals while maintaining efficacy and safety.

III 期研究，DME 中的 PHOTON 和濕性 AMD 中的 PULSAR 正在進行中。 III 期研究的主要目的是確定阿柏西普 8 毫克給藥是否可以延長給藥間隔，同時保持療效和安全性。

Regarding Phase III design in both PHOTON and the PULSAR studies, patients are randomized at baseline to 3 groups: An every 8-week EYLEA 2-milligram arm; an every 12-week 8-milligram aflibercept arm; and every 16-week 8-milligram aflibercept arm following loading doses. The primary endpoint of both these studies is mean change in best-corrected visual acuity or BCVA at week 48. The primary endpoint will be met if 8-milligram aflibercept is non-inferior to 2-milligram EYLEA, while being dosed less frequently.

關於 PHOTON 和 PULSAR 研究中的 III 期設計，患者在基線時被隨機分為 3 組：每 8 週 EYLEA 2 毫克組；每 12 週 8 毫克阿柏西普組；負荷劑量後每 16 週 8 毫克阿柏西普組。這兩項研究的主要終點是第 48 週時最佳矯正視力或 BCVA 的平均變化。如果 8 毫克阿柏西普不劣於 2 毫克 EYLEA，則將達到主要終點，同時給藥頻率較低。

We anticipate results of both PHOTON and PULSAR in the second half of this year, and if positive, to file for regulatory approvals in the U.S. and EU by early 2023.

我們預計 PHOTON 和 PULSAR 將在今年下半年取得成果，如果是積極的，將在 2023 年初之前在美國和歐盟提交監管批准。

Moving to Dupixent, which had a remarkable quarter in terms of clinical updates and regulatory progress. In January, we announced our second positive Phase III study in prurigo nodularis, a disease with high unmet need. At the AAAAI and AAD meeting this year, we presented detailed data from the first positive Phase III study in prurigo nodularis. And we also presented detailed data from our positive Phase III studies in eosinophilic esophagitis and in chronic spontaneous urticaria or CSU in biologic-naive patients.

轉到 Dupixent，該公司在臨床更新和監管進展方面表現出色。 1 月，我們宣布了針對結節性癢疹的第二項陽性 III 期研究，這是一種需求未得到滿足的疾病。在今年的 AAAAI 和 AAD 會議上，我們提供了來自第一個針對結節性癢疹的陽性 III 期研究的詳細數據。我們還提供了來自我們在嗜酸性食管炎和慢性自發性蕁麻疹或未接受生物製劑患者的 CSU 中的積極 III 期研究的詳細數據。

The second Phase III CSU study in patients refractory to omalizumab did not reach statistical significance at an interim analysis. And as announced in March, we have completed enrollment in the first of the 2 Phase III Dupixent studies in COPD and anticipate data from this first study to read out in the first half of next year.

對奧馬珠單抗難治的患者進行的第二項 III 期 CSU 研究在中期分析中未達到統計學意義。正如 3 月份宣布的那樣，我們已經完成了 COPD 的 2 項 III 期 Dupixent 研究中的第一項的註冊，並預計該第一項研究的數據將在明年上半年公佈。

In terms of regulatory progress, we expect an FDA decision for Dupixent in children aged 6 months to 5 years with moderate to severe atopic dermatitis by the new June 9 PDUFA date. We are also excited about an upcoming trial in collaboration with the National Institute of Allergy and Infectious Diseases or the NIAID to assess efficacy and safety of Dupixent for asthma in underserved populations, including Black and Hispanic children in the United States.

在監管進展方面，我們預計 FDA 將在 6 月 9 日新的 PDUFA 日期之前對 6 個月至 5 歲患有中度至重度特應性皮炎的兒童做出 Dupixent 決定。我們還對即將與美國國家過敏和傳染病研究所或 NIAID 合作開展的一項試驗感到興奮，該試驗旨在評估 Dupixent 在服務不足的人群（包括美國的黑人和西班牙裔兒童）中治療哮喘的療效和安全性。

Additionally, we are expecting an FDA decision for our supplementary BLA in eosinophilic esophagitis in patients 12 years and older by August 3, and we completed our regulatory submission for prurigo nodularis indication with FDA acceptance of this application anticipated shortly.

此外，我們預計 FDA 將在 8 月 3 日之前對我們在 12 歲及以上患者的嗜酸性粒細胞性食管炎中的補充 BLA 做出決定，我們完成了我們對結節性癢疹適應症的監管提交，預計 FDA 將很快接受該申請。

Moving to Libtayo and oncology. We are excited about the upcoming milestones in our oncology pipeline, including the FDA decision on our Libtayo chemo combo application for non-small cell lung cancer, data readouts and potential regulatory filings for our hematologic bispecifics as well as initial data readouts from our bispecific antibodies for solid tumors.

搬到 Libtayo 和腫瘤學。我們對我們的腫瘤學管道即將到來的里程碑感到興奮，包括 FDA 對非小細胞肺癌的 Libtayo 化療組合申請的決定、我們的血液學雙特異性藥物的數據讀數和潛在的監管文件，以及我們雙特異性抗體的初始數據讀數對於實體瘤。

In hematology, odronextamab, our CD20xCD3 bispecific, has the potential for best-in-class efficacy in both follicular and diffuse large B-cell lymphoma, and was recently granted Fast Track designation from the FDA for these indications. Detailed results of our first-in-human study were recently published in Lancet Hematology and our registration intent programs in late-stage follicular lymphoma and DLBCL are expected to complete enrollment soon. Based on the safety profile we are observing from an updated step-up dosing regimen, we believe odronextamab has the potential to be administered entirely within the outpatient setting. We look forward to filing with this updated data set later this year pending regulatory feedback from the FDA.

在血液學領域，我們的 CD20xCD3 雙特異性藥物 odronextamab 在濾泡性和瀰漫性大 B 細胞淋巴瘤中具有同類最佳療效的潛力，並且最近獲得了 FDA 對這些適應症的快速通道指定。我們首次人體研究的詳細結果最近發表在《柳葉刀血液學》上，我們在晚期濾泡性淋巴瘤和 DLBCL 中的註冊意向計劃預計將很快完成註冊。根據我們從更新的遞增給藥方案中觀察到的安全性概況，我們認為 odronextamab 有可能完全在門診環境中給藥。我們期待在今年晚些時候提交這個更新的數據集，等待 FDA 的監管反饋。

Development of REGN5458, our BCMAxCD3 bispecific investigated for relapsed or refractory multiple myeloma, remains on track. And pending regulatory feedback, we are planning to submit regulatory approval in the first half of 2023. Studies in earlier lines of the disease, as well as an umbrella study in multiple myeloma investigating 5458 in combination with various standard of care products and investigational candidates, will begin enrollment shortly.

REGN5458 的開發，我們的 BCMAxCD3 雙特異性針對複發或難治性多發性骨髓瘤進行了研究，仍在進行中。在等待監管反饋的情況下，我們計劃在 2023 年上半年提交監管批准。該疾病早期線的研究，以及多發性骨髓瘤的綜合研究，調查 5458 與各種標準護理產品和研究候選人相結合，即將開始招生。

In the second half of the year, we anticipate initial clinical data disclosures for 3 first-in-class bispecifics. Our MUC16xCD3 monotherapy for late-stage ovarian cancer, our METxMET bispecific antibody for MET-altered non-small cell lung cancer, as well as our PSMAxCD28 co-stim bispecific in combination with Libtayo in late-stage prostate cancers. For these late-stage cancers, patients have limited options and showing any durable response would be a promising early sign to be confirmed with additional clinical studies also involving combinations.

在今年下半年，我們預計 3 個一流雙特異性藥物的初步臨床數據披露。我們針對晚期卵巢癌的 MUC16xCD3 單一療法、針對 MET 改變的非小細胞肺癌的 METxMET 雙特異性抗體，以及我們的 PSMAxCD28 聯合刺激雙特異性聯合 Libtayo 在晚期前列腺癌中。對於這些晚期癌症，患者的選擇有限，並且顯示出任何持久的反應將是一個有希望的早期跡象，需要通過也涉及組合的其他臨床研究來證實。

We continue to progress our strategic approach to oncology, which starts with Libtayo as our foundational anti-PD-1 therapy and is augmented by logical combinations utilizing our broad oncology pipeline, whether it involves combining Libtayo with a second checkpoint inhibitor, as we are doing with the LAG-3 antibody in melanoma and other settings, with different combinations of bispecifics or with other agents in our portfolio.

我們繼續推進我們的腫瘤學戰略方法，從 Libtayo 作為我們的基礎抗 PD-1 療法開始，並通過利用我們廣泛的腫瘤學管道的邏輯組合來增強，無論它是否涉及將 Libtayo 與第二種檢查點抑製劑結合，就像我們正在做的那樣在黑色素瘤和其他環境中使用 LAG-3 抗體，使用不同的雙特異性組合或與我們產品組合中的其他藥劑。

Briefly turning to our antibodies against COVID-19. As we recently announced, the FDA extended its review of our REGEN-COV BLA for COVID-19 treatment and prophylaxis, with a new action date of July 13. This extension was due to ongoing discussions with additional data provided to the FDA on pre-exposure prophylaxis use of REGEN-COV. As this regulatory process continues, we are advancing next-generation COVID-19 antibodies and initiated a first-in-human trial with a new candidate in April. We continue to believe that a major unmet need for COVID antibodies is in chronic disease prevention for immunocompromised patients, and future development efforts will be addressing this population.

簡要談談我們針對 COVID-19 的抗體。正如我們最近宣布的那樣，FDA 延長了對我們用於 COVID-19 治療和預防的 REGEN-COV BLA 的審查，新的行動日期為 7 月 13 日。此次延期是由於與向 FDA 提供的額外數據進行的持續討論。暴露預防使用 REGEN-COV。隨著這一監管過程的繼續，我們正在推進下一代 COVID-19 抗體，並於 4 月啟動了一項新候選人的首次人體試驗。我們仍然認為，對 COVID 抗體的主要未滿足需求是免疫功能低下患者的慢性病預防，未來的開發工作將針對這一人群。

Concluding with our Regeneron Genetics medicine, where we and collaborators continue to advance our pipeline.

以我們的 Regeneron 遺傳學藥物結束，我們和合作者繼續推進我們的管道。

For our siRNA collaboration with Alnylam, we are very excited about our first-in-class approach to combining siRNA with antibody therapeutics, designed to maximize effect as well as duration of target blockade. The first of these is our C5 siRNA antibody combination, cemdisiran plus pozelimab. Phase III studies of their combination treatment for paroxysmal nocturnal hemoglobinuria, or PNH, and myasthenia gravis are underway. We will be dosing patients shortly.

對於我們與 Alnyam 的 siRNA 合作，我們對我們將 siRNA 與抗體療法相結合的一流方法感到非常興奮，該方法旨在最大限度地提高效果以及靶標阻斷的持續時間。其中第一個是我們的 C5 siRNA 抗體組合，cemdisiran 加 pozelimab。他們聯合治療陣發性睡眠性血紅蛋白尿症或 PNH 和重症肌無力的 III 期研究正在進行中。我們將很快對患者進行給藥。

In PNH, we are planning to test our combo in both naive and switch patients tested against standard of care therapies, including ravulizumab and eculizumab. Beyond C5, several edition combination programs are in our pre-clinical pipeline.

在 PNH，我們計劃在幼稚和轉換患者中測試我們的組合，針對標準護理療法進行測試，包括 ravulizumab 和 eculizumab。除了 C5，我們的臨床前管道中還有幾個版本組合程序。

We continue to work with Alnylam as leaders in the use of siRNA therapeutics to address non-alcoholic steatohepatitis, or NASH, with several programs addressing novel targets discovered by the Regeneron Genetics Center. First data in NASH patients for ALN-HSD are anticipated mid-2022. We are progressing a second target, PNPLA3 into the clinic later this year, and we have recently identified an additional novel promising target that has been validated by RGC and is awaiting peer review publication.

我們繼續與 Alnylam 合作，作為使用 siRNA 療法來解決非酒精性脂肪性肝炎或 NASH 的領導者，並通過幾個項目解決了再生元遺傳學中心發現的新靶點。 ALN-HSD 的 NASH 患者的第一批數據預計在 2022 年年中。我們正在將第二個靶點 PNPLA3 推進到今年晚些時候進入臨床，我們最近確定了另一個新的有希望的靶點，該靶點已被 RGC 驗證並正在等待同行評審發表。

We are also pleased to report a notable milestone that we and Alnylam initiated our first CNS-targeted siRNA clinical program, targeting amyloid precursor protein or APP, in development for both cerebral amyloid angiopathy and Alzheimer's disease. Showing that this siRNA approach can reduce levels of the target protein in the CNS has the potential to open the door for using this approach in multiple genetically-defined neurodegenerative diseases.

我們也很高興地報告一個顯著的里程碑，我們和 Alnyam 啟動了我們的第一個 CNS 靶向 siRNA 臨床計劃，針對澱粉樣蛋白前體蛋白或 APP，正在開髮用於腦澱粉樣蛋白血管病和阿爾茨海默病。表明這種 siRNA 方法可以降低 CNS 中靶蛋白的水平，有可能為在多種基因定義的神經退行性疾病中使用這種方法打開大門。

In the first quarter, we and Intellia provided an update on our joint CRISPR-based knockout program for transthyretin amyloidosis. Just to remind you, this is the first example of achieving CRISPR-based genomic editing in human beings. Our recent update demonstrated greater than 90% reduction of transthyretin durably achieved for the follow-up observation period in patients with hereditary transthyretin amyloidosis with polyneuropathy as well as acceptable safety observed so far.

在第一季度，我們和 Intellia 提供了關於我們聯合的基於 CRISPR 的轉甲狀腺素蛋白澱粉樣變性淘汰計劃的更新。提醒一下，這是在人類中實現基於 CRISPR 的基因組編輯的第一個例子。我們最近的更新表明，在患有多發性神經病的遺傳性轉甲狀腺素蛋白澱粉樣變性患者的隨訪觀察期內，轉甲狀腺素蛋白持續降低了 90% 以上，並且迄今為止觀察到的安全性是可接受的。

Our genetics medicine portfolio now includes the diverse pipeline of siRNA candidates that we are working on with Alnylam, targeting the diseases of the liver, the brain and the eye as well as our crystal-based approaches in collaboration with Intellia and our viral-targeted gene delivery programs, such as with Decibel addressing congenial forms of hearing loss and other internal programs. While it's still early, we think these groundbreaking approaches have the potential to change the practice of medicine.

我們的遺傳學藥物組合現在包括我們與 Alnylam 合作開發的多種 siRNA 候選藥物，針對肝臟、大腦和眼睛的疾病，以及我們與 Intellia 和我們的病毒靶向基因合作的基於晶體的方法交付計劃，例如通過分貝解決適合性形式的聽力損失和其他內部計劃。雖然現在還為時尚早，但我們認為這些開創性的方法有可能改變醫學實踐。

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

有了這個，我會把電話轉給 Marion。

Thank you, George. Our commercial performance in the first quarter reflects strong execution and the competitive strengths of our diversified and growing portfolio.

謝謝你，喬治。我們第一季度的商業業績反映了我們多元化和不斷增長的投資組合的強大執行力和競爭優勢。

Starting with EYLEA. First quarter global net sales grew 11% year-over-year to nearly $2.4 billion. Over the same period, U.S. net product sales grew 13% to $1.52 billion as EYLEA continues to strengthen its leadership position. Across all proved indications, EYLEA is the preferred anti-VEGF treatment based on its differentiated efficacy and safety profile as well as extensive real-world patient and physician experience.

從 EYLEA 開始。第一季度全球淨銷售額同比增長 11% 至近 24 億美元。同期，隨著 EYLEA 繼續鞏固其領先地位，美國產品淨銷售額增長 13% 至 15.2 億美元。在所有已證明的適應症中，EYLEA 是首選的抗 VEGF 治療，基於其差異化的療效和安全性以及廣泛的真實世界患者和醫生經驗。

As Len mentioned, we are incredibly proud that EYLEA has helped improve or save the vision of patients around the world, with more than 50 million treatments since launch.

正如 Len 提到的，我們為 EYLEA 幫助改善或拯救世界各地患者的視力而感到無比自豪，自推出以來已進行了超過 5000 萬次治療。

Category growth in EYLEA market share continued to increase across all approved indications. In diabetic eye disease, we have seen notable increases across the patient continuum from initial patient diagnosis through to receiving ongoing EYLEA treatment. We believe diabetic eye disease will remain an important source of future growth for EYLEA, as unfortunately, most patients remain underdiagnosed and undertreated.

在所有批准的適應症中，EYLEA 市場份額的類別增長繼續增加。在糖尿病眼病中，我們看到從最初的患者診斷到接受持續的 EYLEA 治療的整個患者連續體顯著增加。我們相信糖尿病眼病仍將是 EYLEA 未來增長的重要來源，因為不幸的是，大多數患者仍然未被充分診斷和治療。

Beyond EYLEA, our investigational aflibercept 8 milligram clinical program continues to generate excitement and a high level of interest within the retinal community. If supported by Phase III results, aflibercept 8 milligram has the potential to be a major enhancement to the anti-VEGF treatment paradigm.

除了 EYLEA，我們的研究性阿柏西普 8 毫克臨床計劃繼續在視網膜界引起興奮和高度興趣。如果得到 III 期結果的支持，阿柏西普 8 毫克有可能成為抗 VEGF 治療範式的重大改進。

In summary, we are confident in Regeneron's ability to maintain leadership over the long term based on our current EYLEA performance and future potential of aflibercept 8 milligram.

總之，基於我們目前的 EYLEA 表現和阿柏西普 8 毫克的未來潛力，我們對 Regeneron 長期保持領先地位的能力充滿信心。

Turning now to Libtayo, with first quarter global net sales of $125 million. In the U.S., net sales were $79 million based on steadily-improving demand across FDA-approved non-melanoma skin cancer indications. The number of prescribers has increased in our non-small cell lung cancer monotherapy indication based on growing brand awareness, positive prescriber feedback and an increasing number of institutions and networks that have included Libtayo in protocols and pathways. We are working to build on this momentum ahead of the potential chemotherapy combination approval expected later this year that would dramatically expand the patient opportunity for Libtayo in lung cancer.

現在轉向 Libtayo，第一季度全球淨銷售額為 1.25 億美元。在美國，基於 FDA 批准的非黑色素瘤皮膚癌適應症的需求穩步提高，淨銷售額為 7900 萬美元。基於品牌知名度的提高、處方者的積極反饋以及越來越多的機構和網絡將 Libtayo 納入協議和途徑，我們的非小細胞肺癌單藥治療適應症的處方者數量有所增加。我們正在努力在今年晚些時候批准潛在的化療組合之前鞏固這一勢頭，這將極大地擴大 Libtayo 治療肺癌的患者機會。

And finally, on to Dupixent, which again achieved remarkable growth for the quarter, demonstrated by a 43% increase in global net sales to over $1.8 billion. Our performance is fueled by a robust uptake across all approved indications as well as an expanding geographic footprint and potential future indications, including use in younger patients.

最後，Dupixent 在本季度再次取得顯著增長，全球淨銷售額增長 43%，超過 18 億美元。我們的業績得益於所有批准的適應症的強勁吸收以及不斷擴大的地理足跡和潛在的未來適應症，包括在年輕患者中的使用。

Dupixent is a transformational medicine for patients and prescribers with significant growth potential ahead. In the U.S., net product sales grew 38% to $1.3 billion. In atopic dermatitis, Dupixent is the first-line systemic treatment in patients with moderate to severe disease. Health care specialists recognize Dupixent's differentiated profile, which includes dual NT-IL-4 and IL-13 mechanism of action, compelling efficacy, rapid symptom relief and well-established safety profile. More than 430,000 patients worldwide are currently on treatment across all indications, and launch preparations are underway for the June potential label expansion for children as young as 6 months of age with atopic dermatitis. We estimate approximately 75,000 biologic eligible children in the U.S. could benefit from Dupixent in this younger age group.

Dupixent 是一種面向患者和處方者的轉型藥物，具有巨大的增長潛力。在美國，淨產品銷售額增長 38% 至 13 億美元。在特應性皮炎中，Dupixent 是中度至重度疾病患者的一線全身治療。醫療保健專家認可 Dupixent 的差異化特徵，其中包括雙重 NT-IL-4 和 IL-13 作用機制、令人信服的療效、快速症狀緩解和完善的安全性特徵。目前，全球有超過 430,000 名患者正在接受各種適應症的治療，並且正在為 6 月針對患有特應性皮炎的 6 個月大兒童的潛在標籤擴展進行啟動準備。我們估計，美國約有 75,000 名符合生物學條件的兒童可以從這個年輕群體的 Dupixent 中受益。

We also look forward to potentially extending Dupixent's label to include additional dermatology conditions, including prurigo nodularis where patients have no currently FDA-approved medicines. Approximately 75,000 U.S. patients with PN are in need of new treatment options and may benefit from Dupixent.

我們還期待著可能將 Dupixent 的標籤擴展到包括其他皮膚病學條件，包括患者目前沒有 FDA 批准的藥物的結節性癢疹。大約 75,000 名美國 PN 患者需要新的治療選擇，並可能從 Dupixent 中受益。

In the highly-competitive biologic asthma indication, Dupixent continues to grow based on its compelling differentiation for health care professionals based on its unique dual mechanism of action, ease of administration, demonstrated safety, broad label and use in both steroid-dependent patients and pediatric patients.

在競爭激烈的生物哮喘適應症中，Dupixent 憑藉其獨特的雙重作用機制、易於管理、安全性、廣泛標籤以及在類固醇依賴患者和兒科中的使用，為醫療保健專業人員提供引人注目的差異化，從而繼續增長耐心。

There are positive prescribing trends from the recent pediatric asthma launch. In nasal polyps, Dupixent remains the preferred choice for both ENTs and allergists, with rapid growth even 3 years after initial launch.

最近推出的兒科哮喘藥物出現了積極的處方趨勢。在鼻息肉方面，Dupixent 仍然是 ENT 和過敏症患者的首選，即使在首次推出 3 年後仍保持快速增長。

Many patients with Type 2 or allergic disease suffer from another concomitant Type 2 disease. For example, in our atopic dermatitis clinical program, 40% of patients also had asthma. Dupixent is differentiated not only by its efficacy and safety profile in individual FDA-approved Type 2 indications, but also its potential to simultaneously address multiple Type 2 diseases in the same patient.

許多患有 2 型或過敏性疾病的患者患有另一種伴隨的 2 型疾病。例如，在我們的特應性皮炎臨床項目中，40% 的患者還患有哮喘。 Dupixent 的獨特之處不僅在於其在 FDA 批准的單個 2 型適應症中的療效和安全性，而且還在於其在同一患者中同時治療多種 2 型疾病的潛力。

We look forward to expanding Dupixent into even more Type 2 diseases. Launch preparations are underway for eosinophilic esophagitis, where there are no FDA-approved medicines and significant unmet need.

我們期待將 Dupixent 擴展到更多的 2 型疾病。嗜酸性食管炎的上市準備工作正在進行中，目前尚無 FDA 批准的藥物和大量未滿足的需求。

Importantly, in our EoE clinical program, approximately 45% of patients also had atopic dermatitis or asthma. If approved in EoE, we estimate at least 50,000 patients in the U.S. could benefit from Dupixent in this indication. Key opinion leaders continue to provide positive feedback on our clinical data, especially given the lack of effective approved treatment alternatives for the patients who suffer from multiple EoE symptoms.

重要的是，在我們的 EoE 臨床計劃中，大約 45% 的患者還患有特應性皮炎或哮喘。如果在 EoE 中獲得批准，我們估計美國至少有 50,000 名患者可以從 Dupixent 中受益。主要意見領袖繼續對我們的臨床數據提供積極的反饋，特別是考慮到對患有多種 EoE 症狀的患者缺乏有效的批准治療方案。

Turning briefly now to Dupixent in markets outside the U.S. In the first quarter, net product sales grew 61% to $485 million. Over the past year, Regeneron has expanded our commercial presence in several key markets outside the United States, and we are encouraged with progress so far integrating our sales efforts with Sanofi.

現在簡要轉向美國以外市場的 Dupixent。第一季度，淨產品銷售額增長 61% 至 4.85 億美元。在過去的一年裡，Regeneron 擴大了我們在美國以外幾個主要市場的商業影響力，我們對迄今為止與賽諾菲整合銷售工作取得的進展感到鼓舞。

In summary, we see significant potential for Dupixent to continue to change the lives of patients and our families, and we will continue to advance initiatives that bring Dupixent to those in need.

總之，我們認為 Dupixent 具有繼續改變患者和我們家人生活的巨大潛力，我們將繼續推進將 Dupixent 帶給有需要的人的舉措。

In conclusion, we are pleased with the performance across our portfolio. We continue to advance our in-line brands and are on track to deliver on future launches, positioning Regeneron for sustained and long-term growth.

總之，我們對我們投資組合的表現感到滿意。我們繼續推進我們的在線品牌，並有望實現未來的發布，將再生元定位為持續和長期的增長。

Now, I'll turn the call over to Bob.

現在，我將把電話轉給 Bob。

Thank you, Marion. My comments today are on Regeneron's financial results, and outlook will be on a non-GAAP basis unless otherwise noted.

謝謝你，馬里恩。我今天的評論是關於 Regeneron 的財務業績，除非另有說明，否則前景將基於非公認會計原則。

Regeneron is off to a strong start in 2022, with double-digit top and bottom line growth in the first quarter driven by execution across the business. First quarter total revenues grew 17% year-over-year to $2.97 billion. Excluding global revenues related to the COVID-19 antibody cocktail, total revenues grew 25%, demonstrating continued strength of our core business. First quarter total diluted net income per share grew 16% to $11.49 on net income of $1.3 billion.

Regeneron 將在 2022 年迎來強勁開局，在整個業務執行的推動下，第一季度實現了兩位數的頂線和底線增長。第一季度總收入同比增長 17% 至 29.7 億美元。不包括與 COVID-19 抗體雞尾酒相關的全球收入，總收入增長了 25%，顯示了我們核心業務的持續實力。第一季度總攤薄後每股淨收入增長 16% 至 11.49 美元，淨收入為 13 億美元。

Beginning with collaboration revenue and starting with Bayer. First quarter 2022 ex-U.S. EYLEA net product sales were $869 million, growing 7% on a reported basis and 13% on a constant currency basis versus first quarter of 2021. Total Bayer collaboration revenue was $385 million, of which we recorded $338 million for our share of net profits from EYLEA sales outside the U.S.

從合作收入開始，從拜耳開始。 2022 年第一季度（美國除外） EYLEA 產品淨銷售額為 8.69 億美元，與 2021 年第一季度相比，按報告基礎增長 7%，按固定匯率計算增長 13%。拜耳合作總收入為 3.85 億美元，其中我們的淨利潤份額為 3.38 億美元EYLEA 在美國以外的銷售

Total Sanofi collaboration revenue was $631 million in the first quarter of 2022 and grew 73% from the prior year, driven by Dupixent. In this quarter, we recognized the $50 million sales milestone upon achieving $2 billion of aggregate ex-U.S. sales for antibody collaboration products on a rolling 12-month basis.

在 Dupixent 的推動下，2022 年第一季度賽諾菲合作總收入為 6.31 億美元，比上年增長 73%。在本季度，我們在實現 20 億美元的美國以外地區總銷售額後，實現了 5000 萬美元的銷售里程碑。抗體合作產品的銷售額以滾動 12 個月為基礎。

Finally, we recorded Roche collaboration revenue of $216 million related to Roche sales of Ronapreve outside the U.S. We do expect additional revenue from this collaboration primarily in the second half of 2022.

最後，我們記錄了與羅氏在美國以外銷售 Ronapreve 相關的羅氏合作收入 2.16 億美元。我們確實預計，主要在 2022 年下半年從這種合作中獲得額外收入。

Regarding REGEN-COV in the U.S. Consistent with our commentary from earlier this year, we did not record any U.S. sales for REGEN-COV in the first quarter of 2022. Absent the execution and fulfillment of an additional government contract, we do not expect to record any U.S. sales for REGEN-COV this year.

關於美國 REGEN-COV 與我們今年早些時候的評論一致，我們在 2022 年第一季度沒有記錄 REGEN-COV 在美國的任何銷售。由於沒有執行和履行額外的政府合同，我們預計不會記錄今年 REGEN-COV 在美國的任何銷售額。

Other revenue in the first quarter of 2022 was $94 million. This includes a $30 million upfront payment from our collaborator, Ultragenyx to market Evkeeza outside of the U.S.

2022 年第一季度的其他收入為 9400 萬美元。這包括我們的合作夥伴 Ultragenyx 為在美國以外市場推廣 Evkeeza 支付的 3000 萬美元預付款。

Moving now to our operating expenses. R&D increased 12% to $751 million, driven by higher headcount and clinical manufacturing costs, including for next-gen COVID antibodies, partially offset by lower clinical trial costs for REGEN-COV.

現在轉到我們的運營費用。研發增長了 12%，達到 7.51 億美元，這主要得益於更高的員工人數和臨床製造成本，包括下一代 COVID 抗體，但部分被 REGEN-COV 的臨床試驗成本降低所抵消。

Starting in the first quarter of 2022, we are changing the presentation of our non-GAAP results to include in-process R&D acquired in connection with asset acquisitions as well as upfront and opt-in payments related to license and collaboration agreements. Going forward, we will now include these charges in both GAAP and non-GAAP results as a new line item called acquired in-process research and development.

從 2022 年第一季度開始，我們將更改非公認會計原則結果的呈現方式，以包括與資產收購相關的正在進行的研發，以及與許可和合作協議相關的預付款和選擇性付款。展望未來，我們現在將這些費用包括在 GAAP 和非 GAAP 結果中，作為一個新的項目，稱為獲得的過程中研究和開發。

In the first quarter of 2022, acquired IP R&D was $28 million, which includes a $20 million opt-in payment to our collaborator, Adicet. In full year 2021, there were $44 million of aggregate upfront payments excluded from non-GAAP R&D expense, all of which were recorded in the fourth quarter of 2021.

2022 年第一季度，收購的 IP 研發為 2800 萬美元，其中包括向我們的合作夥伴 Adicet 支付的 2000 萬美元的選擇加入付款。在 2021 年全年，有 4400 萬美元的總預付款不包括在非公認會計原則的研發費用中，所有這些都記錄在 2021 年第四季度。

SG&A expense increased 10% year-over-year to $389 million, primarily due to costs related to growth initiatives for EYLEA and higher headcount to support our expanding organization. COCM increased 58% year-over-year to $198 million due to higher sales of Dupixent and an increase in shipments of commercial supplies of Praluent for Sanofi outside the United States.

SG&A 費用同比增長 10% 至 3.89 億美元，這主要是由於與 EYLEA 的增長計劃相關的成本以及為支持我們不斷擴大的組織而增加的員工人數。由於 Dupixent 的銷售額增加以及 Praluent 為賽諾菲在美國以外的商業用品的出貨量增加，COCM 同比增長 58% 至 1.98 億美元。

Finally, the first quarter 2022 effective tax rate was 11.6% compared to 10.5% in the prior year.

最後，2022 年第一季度的有效稅率為 11.6%，而去年為 10.5%。

Shifting now to cash flow and the balance sheet. In the first quarter of 2022, Regeneron generated $2 billion in free cash flow, inclusive of collections from the U.S. government for sales of REGEN-COV recorded in the fourth quarter of 2021. It ended the first quarter of 2022 with cash and marketable securities less debt of $11.4 billion.

現在轉向現金流和資產負債表。在 2022 年第一季度，Regeneron 產生了 20 億美元的自由現金流，其中包括美國政府在 2021 年第四季度記錄的 REGEN-COV 銷售收入。截至 2022 年第一季度，其現金和有價證券減去114億美元的債務。

We continue to deliver on our capital allocation priorities. Last month, we announced the agreement to acquire CheckMate Pharmaceuticals for a total equity value of approximately $250 million. Earlier this week, we launched the tender offer for CheckMate shares and expect this deal to close in mid-2022, subject to receipt of regulatory approval and other customary closing conditions.

我們繼續履行我們的資本配置優先事項。上個月，我們宣布以約 2.5 億美元的總股本價值收購 CheckMate Pharmaceuticals。本週早些時候，我們發起了對 CheckMate 股票的要約收購，預計這筆交易將在 2022 年年中完成，但需獲得監管部門的批准和其他慣例成交條件。

In addition, we repurchased $352 million of our shares in the first quarter of 2022. We continue to be opportunistic buyers where we see dislocation between our stock price and our intrinsic valuation.

此外，我們在 2022 年第一季度回購了 3.52 億美元的股票。我們仍然是機會主義買家，我們看到我們的股價與我們的內在估值之間存在錯位。

I will conclude with select updates to our full year 2022 guidance and outlook. We were updating full year R&D guidance to be in the range of $2.9 billion to $3.1 billion. The increase in guidance is driven by clinical manufacturing costs for next-gen COVID antibodies, most of which were recorded in the first quarter, and advancing programs across our pipeline. We also now expect our full year effective tax rate to be in the range of 12% to 14%. A complete summary of our latest full year guidance is available in our press release issued earlier this morning.

最後，我將對我們的 2022 年全年指導和展望進行部分更新。我們將全年研髮指導更新為 29 億至 31 億美元。指導的增加是由下一代 COVID 抗體的臨床製造成本推動的，其中大部分是在第一季度記錄的，以及在我們的管道中推進的項目。我們現在還預計全年有效稅率將在 12% 至 14% 之間。我們今天上午早些時候發布的新聞稿中提供了我們最新的全年指導的完整摘要。

In conclusion, our core business is performing well, and we continue to make investments in our R&D engine supported by our strong financial position, leaving Regeneron well positioned for sustainable long-term growth.

總之，我們的核心業務表現良好，在我們強大的財務狀況的支持下，我們將繼續投資於我們的研發引擎，使再生元處於可持續的長期增長中。

With that, I will pass the call back to Ryan.

這樣，我會將電話轉回給 Ryan。

Thank you, Bob.

謝謝你，鮑勃。

Gigi, that concludes our prepared remarks. We'd now like to open the call for Q&A. With more than 20 callers in the queue and to ensure we are able to address as many questions as possible, we will answer only one question from each caller before moving to the next.

Gigi，我們準備好的發言到此結束。我們現在想打開問答電話。隊列中有 20 多個呼叫者，為了確保我們能夠解決盡可能多的問題，我們將只回答每個呼叫者的一個問題，然後再轉到下一個問題。

Gigi, please go ahead.

吉吉，請繼續。

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

（操作員說明）我們的第一個問題來自 Piper Sandler 的 Chris Raymond。

Just a question maybe for Marion, if I can, on EYLEA and sort of the competitive set. I know you guys have said feedback from the market and the biz now has been somewhat muted, but it's actually kind of striking how different Roche is sort of viewing the reception of the drug. They highlight a lot of enthusiasm from stocks, and I know there's a lot of talk about what will happen after a permanent J-code.

如果可以的話，可能只是對 Marion 的一個問題，關於 EYLEA 和某種競爭性集合。我知道你們已經說過來自市場的反饋，現在商業已經有些沉默，但實際上羅氏對藥物接受度的看法有多麼不同。它們突出了股票的很多熱情，而且我知道有很多關於永久 J 代碼之後會發生什麼的討論。

But I know you guys have a lot of levers to pull here, not least of which is launching the high-dose format of EYLEA. But can you talk a little bit about the rebates, how they are playing into your counter strategy in the maybe near to intermediate term? And how we should be thinking about net pricing going forward?

但我知道你們這裡有很多槓桿，尤其是推出高劑量 EYLEA。但是你能談談回扣嗎，它們在可能接近中期的情況下如何影響你的反制策略？以及我們應該如何考慮未來的淨定價？

Chris, happy to give you some characterization of the market. First, let me comment on EYLEA. And as we reported today, our performance certainly with EYLEA in a very competitive marketplace is quite strong across indications. And certainly, we see very strong performance not only in capturing more than our fair share of the market growth, but also competitive share gains across indications.

克里斯，很高興為您介紹市場的一些特徵。首先，讓我評論一下EYLEA。正如我們今天報導的那樣，我們在競爭激烈的市場中與 EYLEA 的表現在各個方面都非常強勁。當然，我們看到了非常強勁的表現，不僅在獲得超過我們在市場增長中的公平份額，而且在各種跡像中都有競爭力的份額增長。

As a reminder, in rural market, we have about 50% of the VEGF category market share with EYLEA. And in the branded marketplace, over 75% of the branded market share.

提醒一下，在農村市場，我們與 EYLEA 擁有約 50% 的 VEGF 類別市場份額。而在品牌市場中，超過 75% 的品牌市場份額。

I really do think it's probably best to let Roche comment on uptake of their new product in the marketplace. I'll share that prescribers and key opinion leaders come into us on the importance of the demonstrated safety they see with EYLEA, the efficacious profile that we have and certainly the extensive consideration across indications and in-market use that has been incredibly robust.

我真的認為最好讓羅氏評論他們的新產品在市場上的使用情況。我將分享開處方者和主要意見領袖對我們所看到的 EYLEA 所證明的安全性的重要性、我們所擁有的有效形像以及對適應症和市場使用的廣泛考慮的重要性，這已經令人難以置信的強大。

As it relates to other items on pricing and things of that sort, generally, we don't comment. But I certainly will say that looking ahead, we see strong leadership with EYLEA and a profile that is certainly leading the category in terms of experience, uptake and use.

由於它與定價和類似事物的其他項目有關，一般來說，我們不發表評論。但我肯定會說，展望未來，我們看到了 EYLEA 的強大領導力，以及在經驗、吸收和使用方面肯定處於領先地位的形象。

Our next question comes from the line of Cory Kasimov from JPMorgan.

我們的下一個問題來自摩根大通的 Cory Kasimov。

To follow up on EYLEA, I wanted to ask about the high dose formulation. Assuming the results read out as you anticipate, how do you think about this product potentially slotting into the treatment landscape? Is it possible that this could broadly take over from your current dose? Or would you expect it to be primarily used in certain segments of the market?

為了跟進 EYLEA，我想問一下高劑量配方。假設結果如您預期的那樣讀出，您如何看待該產品可能進入治療領域？這是否有可能廣泛取代您目前的劑量？還是您希望它主要用於某些市場領域？

So I think at this point, we'll want to wait and look at product profile as the clinical data matures. And then certainly, as we move into launch preparation planning, we'll be considerate of how the profile matches up against patient need and opportunity. So I think more to come on specifics on uptake. We remain optimistic. But of course, we need to wait and see how the clinical data matures and the profile of product is clarified.

所以我認為在這一點上，隨著臨床數據的成熟，我們將等待並查看產品概況。當然，當我們進入啟動準備計劃時，我們將考慮配置文件如何與患者的需求和機會相匹配。所以我認為更多關於吸收的細節。我們保持樂觀。但當然，我們還需要拭目以待，看看臨床數據如何成熟，產品概況如何明確。

Our next question comes from the line of Evan Seigerman from BMO Capital Markets.

我們的下一個問題來自 BMO Capital Markets 的 Evan Seigerman。

I love if you could expand on some of the rationale behind acquiring or proposing to acquire Checkmate Pharmaceuticals. Anything in the data that was particularly notable when you were doing your diligence that piqued your interest? And do you expect to go forward combining their asset with Libtayo versus say, nivolumab or pembro as they had on their prior trials?

如果你能詳細說明收購或提議收購 Checkmate Pharmaceuticals 背後的一些理由，我很高興。當您盡職盡責時，數據中是否有什麼特別值得注意的地方引起了您的興趣？您是否希望將他們的資產與 Libtayo 結合起來，而不是像他們之前的試驗那樣使用 nivolumab 或 pembro？

I'm sure -- it's Len. I'm sure George would love to stand upon the thinking. But unfortunately, because we just launched the tender offer, we're really not committed to have that discussion. And we'll look forward to that discussion, assuming that the deal closes around the middle of the year as we anticipate.

我確定——是萊恩。我敢肯定，喬治很願意堅持這種想法。但不幸的是，因為我們剛剛啟動了要約收購，所以我們真的不打算進行那個討論。我們將期待這次討論，假設交易如我們預期的那樣在年中左右完成。

Fair enough, Len. Fair enough. That's all right.

很公平，萊恩。很公平。沒關係。

But because we couldn't answer that question, if you get back in the queue, we'll come back to you for another question.

但是因為我們無法回答這個問題，所以如果你回到隊列中，我們會再找你問另一個問題。

Fair enough.

很公平。

Our next question comes from the line of Salveen Richter from Goldman Sachs.

我們的下一個問題來自高盛的 Salveen Richter。

On these initial bispecific datasets in solid tumors in the second half, could you just speak to what exactly we're going to see initially? And then what you would like to -- you would want to see from the dataset in terms of being clinically meaningful?

關於下半年實體瘤的這些初始雙特異性數據集，您能否談談我們最初將看到的內容？然後你想 - 你想從數據集中看到臨床意義？

Well, as I indicated in my remarks, basically, we're going into late-stage patients, heavily, pre-treated. We're hoping to actually be able to report on seeing objective responses, and the number and the duration of the responses is what we're looking for. We would love to be able to see significant numbers of durable responses, showing that each one of these novel agents is really making a difference in the late-stage patients.

好吧，正如我在講話中指出的那樣，基本上，我們將進入晚期患者，經過大量預處理。我們希望能夠真正報告看到的客觀響應，而響應的數量和持續時間正是我們所尋找的。我們希望能夠看到大量持久的反應，表明這些新型藥物中的每一種都確實對晚期患者產生了影響。

That, of course, would open up for each one of them, we think, very important opportunities in terms of both those late-stage settings, but also particularly with logical combinations going back into earlier and earlier stage patients. So each one of them could become then a significant program not only in monetary, but in combination with logical other agents.

當然，我們認為，這將為他們中的每一個打開非常重要的機會，就這些晚期設置而言，而且特別是對於回到早期和早期患者的邏輯組合。因此，它們中的每一個都可以成為一個重要的程序，不僅在貨幣方面，而且在與邏輯上的其他代理結合時。

So as I said, responses with duration is what we're looking for in all 3 of those programs.

所以正如我所說，有持續時間的響應是我們在所有 3 個程序中尋找的。

Just to amplify a little bit what -- to make sure nobody missed what George just said is that, it seems to be the case that with these types of reagents, much as it is the case with other anti-cancer agents, that while you start in the latest, most difficult patients, there is better activity in earlier lines with these kinds of immune reagents. So finding activity in the late, heavily pre-treated would be very encouraging.

只是為了放大一點——為了確保沒有人錯過 George 剛才所說的話，似乎使用這些類型的試劑，就像使用其他抗癌劑一樣，當你從最新、最困難的患者開始，使用這類免疫試劑在較早的系列中具有更好的活性。因此，在後期進行大量預處理的活動將非常令人鼓舞。

Our next question comes from the line of Brian Abrahams from RBC Capital Markets.

我們的下一個問題來自 RBC Capital Markets 的 Brian Abrahams。

Congrats on all the progress. Can you elaborate a little bit more on the safety benefit that you're seeing for odronextamab stepped up dosing? And I guess, what it means in terms of differentiating versus other bispecifics in development, and ultimately, CAR-T, and then your confidence that you'll retain similarly strong efficacy with this dose?

祝賀所有進展。您能否詳細說明您看到的 odronextamab 加量給藥的安全益處？我猜想，這對於區分開發中的其他雙特異性藥物以及最終的 CAR-T 意味著什麼，然後您是否有信心使用該劑量保持同樣強大的功效？

Yes. We actually had initiated the concept for bispecifics in general as we were very early players in the field of this concept of step-up dosing. And what it seems to be -- being confirmed by our own data and other people's data is that when you give them initially at low doses and gradually stepped up to your optimal dose, you are reducing the incidence of severe side effects and particularly cytokine release syndrome.

是的。實際上，我們實際上已經啟動了雙特異性藥物的概念，因為我們是這個逐步給藥概念領域的早期參與者。它似乎是——由我們自己的數據和其他人的數據證實，當你最初以低劑量給予它們並逐漸增加至最佳劑量時，你正在減少嚴重副作用的發生率，特別是細胞因子釋放綜合徵。

We had actually pretty low rates with our original, so our original dosing regimen was also a step-up dosing regimen. But in collaboration with the FDA, we redefined the stepped-up dosing and came up with an even more gradual program. It only extends the timing to get to maximum dose by 1 week, and we're still obviously getting to that same dose.

實際上，我們原來的用藥率非常低，所以我們原來的給藥方案也是一種逐步增加的給藥方案。但與 FDA 合作，我們重新定義了遞增劑量，並提出了一個更加漸進的計劃。它只是將達到最大劑量的時間延長了 1 週，而且我們顯然仍在達到相同的劑量。

And what we're saying is that from the early read from the new step-up dosing, which presumably we'll give you the detailed data at some point in the future, the results are looking very promising. The already low rate of significant cytokine release syndrome that we were seeing, looks like it's depressed even further down to rates where we think, as I stated, we will be able to use this regimen in this approach in the outpatient setting.

我們要說的是，從新的逐步劑量的早期讀取來看，我們可能會在未來的某個時候為您提供詳細的數據，結果看起來非常有希望。我們看到的顯著細胞因子釋放綜合徵的發病率已經很低，看起來它甚至進一步下降到我們認為的比率，正如我所說，我們將能夠在門診環境中以這種方法使用這種方案。

So it's just very promising that we've come up with a safe -- what looks like to be a safe protocol that could be used in outpatient settings. And it's getting to the same maximum dose in a pretty short period of time as well.

因此，我們提出了一個安全的方案是非常有希望的——這看起來像是一個可以在門診環境中使用的安全協議。它也在很短的時間內達到相同的最大劑量。

Our next question comes from the line of Carter Gould from Barclays Capital.

我們的下一個問題來自 Barclays Capital 的 Carter Gould。

One for me. I want to understand, I guess, how you're thinking about your broader CV effort? We've heard from a number of large pharma and biotech companies sort of rededicating themselves to CV recently. And when you map out the indications and products, I'd argue, you have one of the broader pipelines across CV. But you don't really get much credit for it, and probably you and Evkeeza remain relatively small contributors to your sales. So do you see this being a major commercially relevant area for Regeneron going forward? I'd just like to understand your ambitions here a little bit better.

一個給我。我想我想了解一下，您如何看待更廣泛的簡歷工作？最近，我們從許多大型製藥和生物技術公司那裡聽到了重新致力於 CV 的消息。我認為，當您繪製出適應症和產品時，您擁有跨 CV 的更廣泛的管道之一。但是你並沒有真正得到太多的讚譽，而且你和 Evkeeza 對你的銷售額的貢獻可能相對較小。那麼您認為這是 Regeneron 未來的主要商業相關領域嗎？我只是想更好地了解你在這裡的野心。

We have not obviously realized what we think is the full potential of our CV expertise and capabilities, and we are exploring ways on how to do that. Some of which may require us to rethink combinations of both types of reagents and targets, and hopefully, you'll hear more about that. But we would agree, it's -- right now, it's not a major contributor to our near-term performance.

我們顯然還沒有意識到我們認為我們的簡歷專業知識和能力的全部潛力，我們正在探索如何做到這一點的方法。其中一些可能需要我們重新考慮兩種類型的試劑和靶標的組合，希望您能聽到更多相關信息。但我們會同意，它 - 現在，它不是我們近期表現的主要貢獻者。

Our next question comes from the line of Brian Skorney from Baird.

我們的下一個問題來自 Baird 的 Brian Skorney。

This is Luke Herrmann on for Brian Skorney. Could you talk a bit more about 5458, maybe your confidence that the currently enrolling Phase II study will support a filing? Any timeline granularity and combinations you're particularly excited about there?

這是布賴恩斯科尼的盧克赫爾曼。您能否多談談 5458，也許您對目前正在招募的 II 期研究將支持備案的信心？有什麼時間線粒度和組合讓你特別興奮嗎？

Yes. Well, in small numbers, we have very competitive response rates with deep responses and duration that we think, for these late-stage patients, should be able to support registration if we can replicate it in the larger Phase II registrational possible study that we are undertaking. We continue to see a very acceptable safety and tolerability profile. And as you said, this is just sort of the first step in the whole program. We are very excited about combinations, and we're also very excited about moving to earlier lines of therapy.

是的。好吧，在少數情況下，我們有非常有競爭力的反應率和深度反應和持續時間，我們認為，對於這些晚期患者，如果我們可以在更大的 II 期註冊可能研究中復制它，應該能夠支持註冊。承諾。我們繼續看到非常可接受的安全性和耐受性概況。正如你所說，這只是整個計劃的第一步。我們對組合感到非常興奮，我們也對轉向更早的治療線感到非常興奮。

In terms of combinations, as we've talked about before, it's very logical, and the pre-clinical data are very compelling, that combinations with so-called co-stimulatory bispecifics that also bind to a target on the same myeloma cells but now activate what we and others refer to as [signal 2], will be very exciting and has really the potential to enhance responsiveness and deepen responsiveness and deepen duration.

就組合而言，正如我們之前討論過的，它非常合乎邏輯，並且臨床前數據非常引人注目，即與所謂的共刺激雙特異性結合的組合也與相同骨髓瘤細胞上的靶標結合，但現在激活我們和其他人所說的 [信號 2]，將非常令人興奮，並且確實具有增強響應能力、加深響應能力和延長持續時間的潛力。

We have a series of additional next-generation candidate as well that we could layer on top of that next series of logical combinations, which involve these co-stimulatory molecules. And we're also thinking that obviously, as Len already mentioned, going to earlier lines of therapy is only going to increase the responsiveness and the opportunities to get longer and longer responses, and dare I say, even potentially cures.

我們還有一系列額外的下一代候選者，我們可以在下一系列邏輯組合之上進行分層，其中涉及這些共刺激分子。而且我們還認為，顯然，正如 Len 已經提到的，進行早期治療只會增加反應能力和獲得越來越長反應的機會，我敢說，甚至可能治愈。

So that's the basic summary of our programs. Get registration in the late -- late setting by replicating the data that we've seen with our ongoing registration, possible Phase II study. Adding combinations to enhance responses, deepen responsiveness and duration. And three, going into earlier lines of therapy as well.

以上就是我們項目的基本總結。通過複製我們在正在進行的註冊（可能是 II 期研究）中看到的數據，在後期進行註冊。添加組合以增強響應、加深響應和持續時間。第三，也進入早期的治療線。

Our next question comes from the line of Brittany A. Woods from Cowen & Company.

我們的下一個問題來自 Cowen & Company 的 Brittany A. Woods。

This is Brittany on for Tyler. Congrats on another strong quarter. So a multi-part question, a bit related on the REGEN-COV cocktail. For the ongoing studies of the next-gen candidates, when do you expect that it will be filed for approval for the regulatory path forward look like? And also, if we continue to be in a relatively low case period as we enter the endemic phase, what could a pivotal trial ultimately look like there?

這是泰勒的布列塔尼。祝賀另一個強勁的季度。這是一個多部分的問題，與 REGEN-COV 雞尾酒有點相關。對於正在進行的下一代候選藥物的研究，您預計它將在何時提交審批，以了解未來的監管路徑？而且，如果我們在進入流行階段時繼續處於相對較低的病例期，那麼關鍵試驗最終會是什麼樣子？

These are all really great questions. And we are continuing to discuss our regulatory path, both for getting our, hopefully, full approval for our existing cocktail, but also the regulatory path going forward for next-generation cocktails with the FDA. That's an ongoing discussion that has potential to change, and obviously, associated studies to support that program have the potential to change. So we're not, at this point, talking about the details of either. But great questions.

這些都是非常好的問題。我們正在繼續討論我們的監管路徑，希望獲得我們現有雞尾酒的完全批准，以及 FDA 對下一代雞尾酒的監管路徑。這是一個持續的討論，有可能改變，顯然，支持該計劃的相關研究有改變的潛力。因此，在這一點上，我們不是在談論兩者的細節。但是很好的問題。

And suffice it to say the complexities are increased when you have to start thinking about supply as well. So as George said, we're in discussions with the agency about what it would take to get an authorization. But you're always chasing the next variant, and we have probably what we think is greatest end-to-end capabilities in this space as is out there, but still knowing which variant to manufacture for which antibody and how to keep chasing that, it's a fairly complex situation. But we're committed to try and make monoclonal as an important part of the solution. And I think they can be, but it is going to require some artful science, so to speak.

可以說，當您還必須開始考慮供應時，複雜性就會增加。正如喬治所說，我們正在與該機構討論如何獲得授權。但是你總是在追逐下一個變體，我們可能擁有我們認為在這個領域最強大的端到端能力，但仍然知道為哪種抗體製造哪個變體以及如何繼續追逐它，這是一個相當複雜的情況。但我們致力於嘗試將單克隆作為解決方案的重要組成部分。我認為他們可以，但這需要一些巧妙的科學，可以這麼說。

Our next question comes from the line of Dane Leone from Raymond James.

我們的下一個問題來自 Raymond James 的 Dane Leone。

Congratulations on all the progress across all of your programs. One question for me on the PHOTON and PULSAR outcomes. It's been interesting to hear your narrative over many years now through EYLEA, and your team has generally been right in terms of next-generation efforts that have kind of failed to displace EYLEA as the standard of care. And to that point, I'm a little interested from your commentary on the CANDELA readout and how that impacts your interpretation of PHOTON and PULSAR. Meaning, what does your team really think ends up being a differentiated outcome for those patients that are able to treat and extend on the high dose out to q.16 weeks? And does that have to be a comparison to what read out with faricimab studies to make it a compelling drug option or a higher dose option in the market to complement EYLEA?

祝賀您所有程序的所有進展。我有一個關於 PHOTON 和 PULSAR 結果的問題。多年來通過 EYLEA 聽到您的敘述很有趣，而且您的團隊在下一代努力方面通常是正確的，但未能取代 EYLEA 作為護理標準。至此，我對你對 CANDELA 讀數的評論以及它如何影響你對 PHOTON 和 PULSAR 的解釋有點感興趣。意思是，對於那些能夠治療高劑量並延長至 q.16 週的患者，您的團隊真正認為最終會產生什麼差異化結果？這是否必須與 faricimab 研究的結果進行比較，才能使其成為市場上引人注目的藥物選擇或更高劑量的選擇，以補充 EYLEA？

And the context for this, I guess, I'd put it as you guys have generally contended that a lot of these studies comparing against per label EYLEA are not actually fair studies to be running. Faricimab obviously used extra loading dose. But in the real world, the treatment extent of EYLEA versus any of these other agents is actually quite equivalent.

我猜想，我的背景是你們普遍認為，與每個標籤 EYLEA 進行比較的許多這些研究實際上並不是公平的研究。 Faricimab 顯然使用了額外的負荷劑量。但在現實世界中，EYLEA 與任何其他藥物的治療程度實際上是相當的。

So I'd be just interested to hear how you think that contextualization of these high-dose aflibercept studies really inform of who should get the higher dose if and when it becomes available?

所以我很想听聽你認為這些高劑量阿柏西普研究的背景化如何真正告知誰應該獲得更高劑量，如果以及何時可用？

That's going to be obviously a choice for clinicians to decide once they've seen all the data. But I think that an important consideration is still going to be not only the duration, because duration does matter, efficacy, efficacy management, but safety. And I think the distinct advantage we have with high-dose EYLEA is that from a molecular point of view, whether you're having immunologic reactions and those sorts of things, EYLEA is a very well-known entity. If we can transition to a higher dose with the same kind of safety and allow for longer duration, I think that is a more attractive paradigm in switching to a new molecular mechanism of action with unproven safety with 50 million injections behind it. And frankly, I do think even the FDA views the -- when you're changing dosing paradigms of the same molecule as different when you're bringing in a new molecule.

這顯然是臨床醫生在看到所有數據後做出決定的選擇。但我認為一個重要的考慮因素仍然不僅是持續時間，因為持續時間確實很重要，功效，功效管理，還有安全性。而且我認為我們使用高劑量 EYLEA 的明顯優勢在於，從分子的角度來看，無論您是否有免疫反應和諸如此類的事情，EYLEA 都是一個非常知名的實體。如果我們可以轉換到具有相同安全性的更高劑量並允許更長的持續時間，我認為這是一個更有吸引力的範例，可以轉換到具有未經證實的安全性的新分子作用機制，其背後有 5000 萬次注射。坦率地說，我認為即使是 FDA 也認為 - 當你改變相同分子的劑量範式時，當你引入新分子時會有所不同。

So we can't say and we wouldn't dare to speak for what clinicians will do once they see the data, but we do feel strongly that having the same EYLEA backbone, if we get the safety that we anticipate thus far from the small CANDELA study, and we get the kind of extension of duration, perhaps more driving to look at the actual numbers. I think that sort of transition is more efficient than transitions that may occur with new reagents.

所以我們不能說也不敢說臨床醫生在看到數據後會做什麼，但我們確實強烈認為擁有相同的 EYLEA 主幹，如果我們得到我們迄今為止預期的安全性，而不是小CANDELA研究，我們得到了那種持續時間的延長，也許更多的驅動看實際數字。我認為這種轉變比新試劑可能發生的轉變更有效。

Our next question comes from the line of Charlie Yang from Morgan Stanley.

我們的下一個問題來自摩根士丹利的 Charlie Yang。

This is Charlie Yang on for Matthew. I just want to follow up on the REGN5458, BCMA bispecific. I guess my question here is, given the competitor is ahead and potentially account getting approval later this year, and they are already testing in combination with DARZALEX, for example, I'm just curious about kind of your confidence on the 5458 in terms of its outlook. And maybe just provide some thoughts on the competitive landscape and the commercial opportunity across different line of settings?

這是馬修的查理楊。我只想跟進 REGN5458，BCMA 雙特異性。我想我的問題是，鑑於競爭對手領先並且可能在今年晚些時候獲得批准，並且他們已經在與 DARZALEX 組合進行測試，例如，我只是好奇你對 5458 的信心它的前景。也許只是提供一些關於不同設置線的競爭格局和商業機會的想法？

Yes. We think being marginally ahead or behind here isn't really going to mean all that much. It's how good your actual agent is. And also, of course, what opportunities you have for combinations. And so as we said, if we can reproduce the efficacy we've seen in our initial studies in our potentially pivotal Phase II program, that will make it a very, very competitive agent in terms of efficacy, and that's what obviously really matters.

是的。我們認為在這裡稍微領先或落後並不意味著什麼。你的實際代理有多好。當然，還有你有什麼組合的機會。正如我們所說，如果我們能夠在我們潛在的關鍵 II 期計劃中重現我們在初步研究中看到的功效，那將使其在功效方面成為非常非常有競爭力的藥物，這顯然是真正重要的。

But also in terms of combinations, we do believe that we have some of the most interesting and potentially game-changing combinations with novel agents such as these co-stimulatory bispecifics that are whole different opportunities than combinations with traditional -- more traditional agents. So it can take the efficacy that hopefully, we will see with the monotherapy, both in the late-stage setting but just as, if not more importantly, in the earlier stage settings, and really extend and take it to another level.

但在組合方面，我們確實相信我們擁有一些最有趣且可能改變遊戲規則的新型藥物組合，例如這些共刺激雙特異性藥物，與與傳統藥物組合的機會完全不同——更傳統的藥物。因此，它可以發揮我們希望在單一療法中看到的效果，無論是在晚期環境中，還是在早期環境中，如果不是更重要的話，並且真正將其擴展到另一個層次。

And so being a little bit ahead or behind here is not going to be as important as producing really good data. Combinations, we think it's really whether you can really come up and you have in your portfolio very interesting logical combinations that can really be game-changing. And we think that we have those opportunities, which is why we're so excited about this program.

因此，在這裡稍微領先或落後並不像產生真正好的數據那麼重要。組合，我們認為這真的取決於你是否真的能想出並且你的投資組合中有非常有趣的邏輯組合，它們真的可以改變遊戲規則。我們認為我們有這些機會，這就是我們對這個項目如此興奮的原因。

Our next question comes from the line of Mohit Bansal from Wells Fargo.

我們的下一個問題來自富國銀行的 Mohit Bansal。

Great. Thank you for squeezing me in. Maybe a question on EYLEA, high-dose EYLEA. George, I would love to get your take on the design of the DME trial. It seems like there are 5 monthly doses in the 2-milligram arm just like label, but only 3 for the 8-milligram arm. Could you please walk us through the rationale behind this difference? And wouldn't it put high-dose EYLEA at a disadvantage?

偉大的。謝謝你把我擠進去。也許是關於 EYLEA 的問題，高劑量 EYLEA。喬治，我很想听聽您對 DME 試驗設計的看法。就像標籤一樣，2 毫克的手臂似乎有 5 個月的劑量，但 8 毫克的手臂只有 3 次。您能告訴我們這種差異背後的基本原理嗎？它不會讓高劑量的 EYLEA 處於劣勢嗎？

Yes. Well, certainly, the whole goal of the high-dose EYLEA is to deliver the same efficacy and safety, as Len said, safety being very important, but with the reduced injection schedule. And so honestly, it is, as you said, more challenging to be accomplishing the results in PHOTON with less loading injections than for the 2-milligram EYLEA. But that is the goal with the high dose aflibercept. So it is challenging, but it is the higher dose. That's what the goal is, and I guess the data will speak.

是的。嗯，當然，高劑量 EYLEA 的整個目標是提供相同的功效和安全性，正如 Len 所說，安全性非常重要，但注射時間減少了。老實說，正如您所說，在 PHOTON 中以更少的負載注射完成結果比使用 2 毫克 EYLEA 更具挑戰性。但這是高劑量阿柏西普的目標。所以這是具有挑戰性的，但它是更高的劑量。這就是目標，我想數據會說話。

Yes. And I think we could eliminate. If we gave too high the loading dose, obviously, it might complicate some of the efficacy readouts. But as George said, I think the -- based on what we know when we designed it, this looks like it could -- we're optimistic.

是的。我認為我們可以消除。顯然，如果我們給予過高的負荷劑量，可能會使某些功效讀數複雜化。但正如喬治所說，我認為 - 基於我們在設計時所知道的，這看起來可以 - 我們很樂觀。

All right. Thank you. I think we're done.

好的。謝謝你。我想我們已經完成了。

Gigi, we conclude the call.

吉吉，我們結束通話。

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

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連接。