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.

歡迎參加再生元製藥公司2022年第一季財報電話會議。我是Gigi，將擔任本次電話會議的接線生。 （接線生說明）請注意，本次會議正在錄音。

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

現在我將把電話交給投資者關係副總裁瑞安·克羅。您可以開始了。

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Gigi。各位全球聽眾，早安、下午好、晚上好。感謝您對Regeneron的關注，歡迎您參加我們2022年第一季財報電話會議。本次網路直播的存檔將在會議結束後不久發佈在我們的投資者關係網站上。

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.

今天與我一同出席的有：創始人、總裁兼首席執行官倫納德·施萊弗博士；聯合創始人、總裁兼首席科學官喬治·揚科波洛斯博士；執行副總裁兼商務主管瑪麗昂·麥考特；以及執行副總裁兼首席財務官鮑勃·蘭德里。在我們分別致詞後，我們將進入問答環節。

I would 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.

我還要提醒各位，今天電話會議的發言包含Regeneron公司的前瞻性陳述。這些陳述可能包括但不限於與Regeneron及其產品和業務、財務預測和指導、研發項目及相關預期里程碑、合作、財務、監管事宜、支付方覆蓋範圍和報銷問題、知識產權、未決訴訟和其他程序以及競爭相關的陳述。每項前瞻性陳述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預測的結果和事件有重大差異。

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.

關於這些及其他重大風險的更完整描述，請參閱Regeneron向美國證券交易委員會提交的文件，包括其截至2022年3月31日的季度報告（10-Q表格），該報告已於今天上午提交給美國證券交易委員會。 Regeneron不承擔任何更新前瞻性聲明的義務，無論是因為出現新資訊、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 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，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的調節信息，請參閱我們網站上發布的財務業績新聞稿。

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

通話結束後，鮑勃·蘭德里和投資者關係團隊將隨時解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構成對CheckMate Pharmaceuticals, Inc.證券的購買要約，也不構成對CheckMate Pharmaceuticals, Inc.證券的出售要約邀請。關於對CheckMate股票的要約收購，Regeneron和Scandinavian Acquisition Sub, Inc.已向美國證券交易委員會（SEC）提交了附表TO的要約收購聲明及其他要約收購材料，CheckMate也已向SEC提交了附表14D-9的徵求建議聲明。 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（視情況而定）或SEC的網站www.sec.gov上免費取得。

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.

您應該仔細審查提交給美國證券交易委員會的此類材料，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?

那麼，現在讓我把電話交給我們的總裁兼執行長倫‧施萊弗博士。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.

謝謝瑞恩。歡迎參加你的首次財報電話會議。希望所有利害關係人和我一起熱烈歡迎你加入再生元團隊。也感謝所有參加本次電話會議的各位。

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.

繼 2021 年的卓越表現之後，Regeneron 在 2022 年也取得了強勁的開局。我們第一季的業績得益於全公司的高效執行，我們持續投資於差異化研發，並專注於商業績效，從而持續獲得回報。

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.

我們也透過審慎的資本配置繼續提升股東價值，包括今年前三個月回購約 3.5 億美元的股票。

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.

在財務業績方面，我們實現了強勁的兩位數營收和非GAAP每股收益成長。若不計入新冠病毒抗體雞尾酒療法研發帶來的營收貢獻，營收成長25%，這反映了我們日益多元化的核心業務持續蓬勃發展。

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.

EYLEA全球淨銷售額在第一季成長11%，達到近24億美元，其中美國市場營收達15億美元，年增13%，超過了美國抗VEGF藥物市場的整體成長速度。 EYLEA又迎來了一個里程碑：經過十餘年的發展，其全球注射量近期突破5000萬次，這充分證明了其卓越的療效和安全性。

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 將繼續代表著重要的長期成長機會，這主要得益於人口老化、糖尿病患者群體快速成長以及我們正在研究的 aflibercept 8 毫克有望補充和增強我們的視網膜產品線。

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.

就Dupixent而言，第一季全球營收超過18億美元，較去年同期成長43%，這得益於我們不斷重新定義2型發炎性疾病的治療方式。我們仍有很大的機會在已核准的適應症領域惠及更多患者，並期待今年稍後和2023年初在美國推出Dupixent的7項新適應症，包括兒童異位性皮膚炎、嗜酸性食道炎和結節性癢疹。目前，美國約有20萬名患者患有這三種疾病，但尚無核准的——即沒有獲得FDA批准的——全身性治療方案。

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.

在腫瘤領域，Libtayo 在 FDA 批准的非黑色素瘤皮膚癌適應症中持續佔據顯著市場份額，並被視為標準療法。除了皮膚腫瘤外，我們在美國單藥治療非小細胞肺癌方面也開始取得進展，這為今年稍後 Libtayo 聯合化療的潛在上市奠定了基礎，屆時 Libtayo 將能夠惠及更多非小細胞肺癌患者。

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，我們仍然認為 Libtayo 是我們免疫腫瘤學發展策略的基礎，並期望它能與我們研發管線中的各種抗體、雙特異性抗體和共刺激雙特異性抗體以及其他管線候選藥物（包括我們合作研發的藥物）相結合，成為我們研究性臨床項目的支柱。

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.

今年四月，我們宣布達成收購CheckMate Pharmaceuticals的協議，這是Regeneron首次收購該公司。交易完成後，我們預期CheckMate的差異化Toll受體9激動劑vidutolimod將為Regeneron針對難治性癌症的潛在療法管線增添一種極具前景的新療法。

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，我們仍將按計劃在今年下半年分享針對難治性實體瘤（如卵巢癌和前列腺癌）的數據；提交 odronextamab 的生物製品許可申請 (BLA)，odronextamab 是一種潛在的同類最佳 CD20xCD3 雙特異性抗體，用於治療難治性 BCMA 淋巴瘤；並推進 REGN5458（我們的雙特異性抗體的 BCMACD3）。

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，關於我們持續進行的COVID-19應對措施，隨著疫情可能進入地方性流行階段，再生元仍致力於對抗病毒。我們堅信單株抗體將繼續發揮重要作用，尤其是在保護免疫功能低下、對COVID-19疫苗反應不足的個體，以及治療口服抗病毒藥物耐受性差或可能引發嚴重藥物交互作用的感染患者方面。我們正在推動下一代抗體的研發，這些抗體旨在對抗多種變異株，包括Omicron譜系的變異株，並在上個月啟動了首次人體試驗。

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

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，我們對在研產品組合強勁的商業發展勢頭以及今年迄今在推動研發管線方面取得的進展感到非常振奮。在2022年剩餘的時間裡，我們預計將獲得至多8項美國和歐盟監管機構的批准，提交至多4項美國或歐盟監管機構的申請，公佈8毫克劑量阿柏西普的關鍵數據，以及其他研發管線項目的各項數據，喬治將對此進行詳細介紹。

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.

我們對公司的長期前景仍然充滿信心，我們的研發管線持續高效運轉，並且我們擁有強勁的財務實力，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，我將把電話交給喬治。

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

謝謝你，Len，我今天就從眼科開始。

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.

在最近舉行的血管生成會議上，我們公佈了阿柏西普8毫克治療濕性老年黃斑部病變（AMD）患者的II期CANDELA研究的令人鼓舞的結果。 CANDELA研究達到了主要安全性終點，在第44週未觀察到新的安全性訊號；療效終點方面，在第44週，阿柏西普8毫克在視力、乾燥和其他解剖學指標方面均優於對照組。

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.

目前，針對糖尿病性黃斑水腫（DME）的PHOTON研究和針對濕性老年黃斑部病變（AMD）的PULSAR研究正在進行中。 III期研究的主要目的是確定阿柏西普8毫克劑量能否在維持療效和安全性的前提下，延長給藥間隔。

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.

在PHOTON和PULSAR兩項研究的III期設計中，患者在基線時被隨機分配到3個組：每8週接受一次2毫克EYLEA治療的組；每12週接受一次8毫克阿柏西普治療的組；以及在接受負荷劑量後，每16週接受一次8毫克阿柏西普治療的組。這兩項研究的主要終點是第48週時最佳矯正視力（BCVA）的平均變化。如果8毫克阿柏西普在給藥頻率較低的情況下，療效不劣於2毫克EYLEA，則可達到主要終點。

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 試驗結果將於今年下半年公佈，如果結果積極，我們將在 2023 年初向美國​​和歐盟提交監管審批申請。

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.

接下來談談Dupixent，該藥物在本季度取得了顯著的臨床進展和監管方面的突破。 1月份，我們宣布了針對結節性癢疹（一種未被滿足的重大醫療需求疾病）的第二項陽性III期研究結果。在今年的AAAAI和AAD年會上，我們發表了首個針對結節性癢疹的陽性III期研究的詳細數據。此外，我們也發表了嗜酸性食道炎和慢性自發性蕁麻疹（CSU，生物製劑初治患者）的陽性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.

針對奧馬珠單抗難治性患者的第二項 III 期 CSU 研究在中期分析中未達統計學意義。正如我們在三月宣布的那樣，我們已完成兩項 Dupixent III 期 COPD 研究的第一項的受試者招募，預計將於明年上半年公佈該研究的數據。

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，我們預期FDA將在新的PDUFA截止日期6月9日之前，就Dupixent用於治療6個月至5歲中重度異位性皮膚炎兒童的適應症做出決定。此外，我們也對即將與美國國家過敏症和傳染病研究所（NIAID）合作進行的一項試驗感到興奮，該試驗旨在評估Dupixent在包括美國黑人和西班牙裔兒童在內的弱勢群體中治療氣喘的療效和安全性。

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 將於 8 月 3 日前對我們針對 12 歲及以上嗜酸性食道炎患者的補充生物製品許可申請 (BLA) 做出決定，並且我們已經完成了針對結節性癢疹適應症的監管申請，預計 FDA 很快就會接受該申請。

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.

轉向Libtayo和腫瘤領域。我們對腫瘤產品線即將取得的里程碑進展感到興奮，包括FDA對我們用於治療非小細胞肺癌的Libtayo化療組合申請的決定、血液學雙特異性抗體的數據解讀和潛在的監管申報，以及我們用於治療實體瘤的雙特異性抗體的初步數據解讀。

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雙特異性抗體odronextamab在濾泡性淋巴瘤和瀰漫性大B細胞淋巴瘤方面均具有同類最佳的療效潛力，並已獲得FDA授予的快速通道資格。我們首次人體試驗的詳細結果已於近期發表在《柳葉刀血液學》雜誌上，我們針對晚期濾泡性淋巴瘤和瀰漫性大B細胞淋巴瘤的註冊意向項目預計很快將完成患者招募。基於我們從更新的遞增給藥方案中觀察到的安全性，我們認為odronextamab有望完全在門診給藥。我們期待在今年稍後提交包含更新數據的申請，並等待FDA的監管回饋。

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.

我們正在研發的治療復發或難治性多發性骨髓瘤的BCMAxCD3雙特異性抗體REGN5458，其研發工作進展順利。在獲得監管部門回饋後，我們計劃於2023年上半年提交監管審批申請。針對早期多發性骨髓瘤的研究，以及一項旨在評估REGN5458聯合多種標準治療藥物和在研藥物治療多發性骨髓瘤的傘式研究，即將啟動患者招募。

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.

今年下半年，我們預計將公佈三款首創雙特異性抗體的初步臨床數據。這三款抗體分別是：用於治療晚期卵巢癌的MUC16xCD3單藥療法、用於治療MET基因改變的非小細胞肺癌的METxMET雙特異性抗體，以及與Libtayo聯合用於治療晚期前列腺癌的PSMAxCD28共刺激雙特異性抗體。對於這些晚期癌症，患者的治療選擇有限，因此任何持久的療效都將是一個令人鼓舞的早期跡象，需要透過包括聯合用藥在內的更多臨床研究來證實。

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.

我們繼續推進腫瘤學策略方針，以 Libtayo 作為我們的基礎抗 PD-1 療法，並透過利用我們廣泛的腫瘤產品線進行合理的組合來增強，無論是將 Libtayo 與第二種檢查點抑制劑結合（就像我們在黑色素瘤和其他疾病中使用 LAG-3 抗體一樣），還是與不同的雙抗體組合，或與我們產品中的其他藥物特異性組合，或與我們產品中的其他藥物特異性組合，或其他藥物結合。

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.

簡單談談我們針對新冠病毒的抗體。正如我們近期宣布的，FDA已延長了我們用於新冠病毒治療和預防的REGEN-COV生物製品許可申請（BLA）的審查期限，新的審批日期為7月13日。此次延期是由於我們與FDA就REGEN-COV暴露前預防用途的補充數據進行了持續討論。在監管流程推進的同時，我們也正在推動下一代新冠病毒抗體的研發，並於4月啟動了一項針對新候選藥物的首次人體試驗。我們仍然認為，新冠病毒抗體的一個主要未滿足需求在於免疫功能低下患者的慢性疾病預防，未來的研發工作將著重於這一人群。

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

最後，我們來談談 Regeneron Genetics 的藥物研發，我們和合作夥伴將繼續推動我們的研發管線。

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.

我們與Alnylam公司在siRNA領域的合作非常令人振奮，我們首創的siRNA與抗體療法聯合療法旨在最大限度地提高靶點阻斷的療效和持續時間。首個此類聯合療法是我們的C5 siRNA抗體組合，即cemdisiran聯合pozelimab。目前，針對陣發性睡眠性血紅素尿症（PNH）和重症肌無力的III期臨床試驗正在進行中。我們將很快開始對患者進行給藥。

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.

在陣發性睡眠性血紅蛋白尿症（PNH）領域，我們計劃在初治患者和轉換治療患者中測試我們的聯合療法，並將其與包括拉武利珠單抗和依庫珠單抗在內的標準療法進行比較。除C5外，我們還有多個聯合療法項目處於臨床前研發階段。

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公司合作，該公司是siRNA療法治療非酒精性脂肪性肝炎（NASH）領域的領導者。我們開展了多個項目，旨在開發由Regeneron遺傳學中心發現的新標靶。 ALN-HSD在NASH患者中的首批數據預計將於2022年中期公佈。我們正在推進第二個標靶PNPLA3的臨床試驗，預計今年稍後啟動。此外，我們最近還發現了一個新的、極具潛力的靶點，該靶點已由RGC驗證，目前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.

我們很高興地宣布一項重要的里程碑：我們與Alnylam公司共同啟動了首個靶向中樞神經系統（CNS）的siRNA臨床項目，該項目靶向澱粉樣前體蛋白（APP），旨在治療腦澱粉樣血管病變和阿茲海默症。研究表明，這種siRNA方法能夠降低中樞神經系統中目標蛋白的水平，這有望為該方法在多種基因明確的神經退化性疾病中的應用打開大門。

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.

第一季度，我們與Intellia公司聯合發布了基於CRISPR技術的轉甲狀腺素蛋白澱粉樣變性基因敲除計畫的最新進展。需要提醒的是，這是CRISPR技術在人類身上實現基因組編輯的首例。我們近期發表的數據顯示，在患有遺傳性轉甲狀腺素蛋白澱粉樣變性伴隨多發性神經病變的患​​者中，轉甲狀腺素蛋白水平在追蹤觀察期內持續降低超過90%，且目前觀察到的安全性良好。

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.

我們的基因藥物產品組合目前包括與Alnylam合作開發的多種siRNA候選藥物，這些藥物針對肝臟、大腦和眼睛疾病；此外，還包括與Intellia合作開發的基於晶體的基因療法；以及我們利用病毒載體進行基因遞送的項目，例如與Decibel合作開發的針對先天性聽力損失的療法，以及其他內部項目。雖然目前仍處於早期階段，但我們認為這些突破性的方法有望改變醫學實踐。

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 commercial performance in the first quarter reflects strong execution and the competitive strengths of our diversified and growing portfolio.

謝謝你，喬治。我們第一季的商業業績反映了我們強有力的執行力以及多元化且不斷增長的產品組合所帶來的競爭優勢。

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.

首先來看安麗（EYLEA）。第一季全球淨銷售額年增11%，接近24億美元。同期，安麗在美國的淨銷售額成長13%，達到15.2億美元，安麗持續鞏固其市場領先地位。在所有已證實的適應症中，安麗憑藉其卓越的療效和安全性，以及廣泛的真實世界患者和醫生經驗，成為首選的抗VEGF治療藥物。

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 所提到的，我們非常自豪的是，EYLEA 自上市以來已幫助改善或挽救了世界各地患者的視力，累計治療量超過 5000 萬次。

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.

EYLEA在所有核准適應症的市佔率持續成長。在糖尿病眼疾領域，我們觀察到從患者初次診斷到接受EYLEA持續治療的整個治療過程中，使用率均顯著提高。我們相信，糖尿病眼疾仍將是EYLEA未來成長的重要來源，因為遺憾的是，大多數患者仍未被充分診斷​​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 研究之外，我們正在進行的阿柏西普 8 毫克臨床試驗計畫也持續引起視網膜領域的高度關注和關注。如果 III 期臨床試驗結果支持，阿柏西普 8 毫克有望成為抗 VEGF 治療模式的重大革新。

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.

總而言之，基於我們目前 EYLEA 的表現和 aflibercept 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.

現在來看Libtayo，第一季全球淨銷售額達1.25億美元。在美國，淨銷售額為7,900萬美元，這得益於FDA批准的非黑色素瘤皮膚癌適應症需求的持續成長。在非小細胞肺癌單藥治療適應症方面，處方醫生數量有所增加，這主要歸功於品牌知名度的提升、處方醫生的積極反饋，以及越來越多的醫療機構和網絡將Libtayo納入治療方案和路徑。我們正努力鞏固這一發展勢頭，以期在今年稍後獲得化療聯合用藥的批准，這將極大地拓展Libtayo在肺癌治療領域的患者群體。

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，讓我們來看看Dupixent，該產品本季再次實現了顯著成長，全球淨銷售額成長43%，超過18億美元。這項業績得益於所有已獲準適應症的強勁市場需求，以及不斷擴大的地域覆蓋範圍和潛在的未來適應症，包括用於年輕患者。

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 是一種具有變革意義的藥物，對患者和處方醫生都極具價值，並擁有巨大的成長潛力。在美國，其淨銷售額成長了 38%，達到 13 億美元。在異位性皮膚炎領域，Dupixent 是中度至重度患者的第一線系統性治療藥物。醫療專家認可 Dupixent 的獨特優勢，包括雙重 NT-IL-4 和 IL-13 作用機制、顯著的療效、快速緩解症狀以及良好的安全性。目前，全球已有超過 43 萬名患者正在接受 Dupixent 治療，涵蓋所有適應症。該公司正在積極籌備，計劃於 6 月將 Dupixent 的適應症擴展至 6 個月及以上的異位性皮膚炎兒童。我們估計，在美國，約有 7.5 萬名符合生物製劑治療條件的兒童有望從 Dupixent 中獲益。

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.

我們也期待未來能將Dupixent的適應症擴展至其他皮膚病，包括目前尚無FDA核准藥物治療的結節性癢疹。美國約有75,000名結節性癢疹患者需要新的治療方案，而Dupixent有望為他們帶來益處。

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.

在競爭激烈的生物製劑氣喘適應症領域，Dupixent 憑藉其獨特的雙重作用機制、易於給藥、已證實的安全性、廣泛的適應症以及在類固醇依賴型患者和兒科患者中的應用，持續增長，為醫療保健專業人員提供了引人注目的差異化優勢。

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.

近期兒科氣喘藥物上市後，處方量呈現正向趨勢。在鼻息肉治療方面，Dupixent 仍然是耳鼻喉科醫生和過敏科醫生的首選藥物，即使在上市三年後，其銷售仍保持快速增長。

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.

許多患有第 2 型過敏性疾病的患者同時也患有其他 2 型疾病。例如，在我們進行的異位性皮膚炎臨床計畫中，40% 的患者同時患有氣喘。 Dupixent 的獨特之處不僅在於其在 FDA 批准的各項 2 型疾病適應症中的療效和安全性，還在於其能夠同時治療同一患者的多種 2 型疾病。

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的應用範圍擴展到更多第二型糖尿病疾病領域。目前，針對嗜酸性粒細胞性食道炎的上市準備工作正在進行中，該領域尚無FDA批准的藥物，存在巨大的未滿足醫療需求。

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.

值得注意的是，在我們的嗜酸性粒細胞性食道炎（EoE）臨床計畫中，約有45%的患者同時患有異位性皮膚炎或氣喘。如果Dupixent核准用於治療EoE，我們估計美國至少有5萬名患者可從中獲益。鑑於目前缺乏針對多種EoE症狀患者的有效治療方案，關鍵意見領袖持續對我們的臨床數據給予正面回饋。

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.

現在簡單談談Dupixent在美國以外的市場表現。第一季度，產品淨銷售額成長61%，達到4.85億美元。過去一年，Regeneron已在美國以外的幾個關鍵市場擴大了商業版圖，我們對目前與賽諾菲銷售整合的進展感到鼓舞。

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.

總而言之，我們看到了 Dupixent 的巨大潛力，它將繼續改變患者及其家人的生活，我們將繼續推進各項舉措，將 Dupixent 帶給有需要的人。

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，我們對旗下所有產品的表現都感到滿意。我們將繼續推動現有品牌的發展，並按計劃推進未來產品的上市，這將使Regeneron實現持續的長期成長。

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

現在，我把電話交給鮑伯。

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，瑪莉安。我今天的評論是關於再生元公司的財務業績，除非另有說明，否則展望將基於非GAAP準則。

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.

2022年開始，Regeneron表現強勁，第一季營收及利潤均達到兩位數成長，主要得益於公司各部門的高效執行。第一季總營收年增17%至29.7億美元。若不計入與新冠病毒抗體雞尾酒療法相關的全球營收，總營收成長25%，彰顯了公司核心業務的持續強勁勢頭。第一季稀釋後每股淨收益成長16%至11.49美元，淨利達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.

首先從合作收入和拜耳公司開始。 2022年第一季，除美國以外，EYLEA淨產品銷售額為8.69億美元，以報告匯率計算年增7%，以固定匯率計算年增13%。拜耳公司合作總收入為3.85億美元，其中3.38億美元是我們應得的美國以外EYLEA銷售淨利份額。

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.

2022年第一季，賽諾菲合作項目總營收為6.31億美元，較去年同期成長73%，主要得益於Dupixent的強勁表現。本季度，我們實現了5,000萬美元的銷售里程碑，同時，過去12個月抗體合作產品在美國以外的累積銷售額也達到了20億美元。

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，我們記錄了與羅氏合作相關的 2.16 億美元收入，與羅氏在美國以外地區銷售 Ronapreve 有關。我們預計，這項合作帶來的額外收入主要將在 2022 年下半年產生。

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 REGEN-COV 在美國的情況，與我們今年稍早的評論一致，我們在 2022 年第一季沒有錄得 REGEN-COV 在美國的任何銷售額。如果沒有新的政府合約的執行和履行，我們預計今年不會錄得 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 年第一季其他收入為 9,400 萬美元。其中包括我們的合作夥伴 Ultragenyx 支付的 3000 萬美元預付款，用於在美國以外地區推廣 Evkeeza。

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.

接下來是營運費用。研發費用增加12%至7.51億美元，主要原因是人員增加和臨床生產成本上升，包括下一代新冠抗體的研發成本，但REGEN-COV臨床試驗成本的降低部分抵消了這一增長。

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.

自2022年第一季起，我們將調整非GAAP財務報表的列報方式，將與資產收購相關的在研研發項目以及與許可和合作協議相關的預付款和選擇加入付款納入其中。今後，我們將把這些費用作為一項名為「收購在研研發項目」的新項目，同時計入GAAP和非GAAP財務報表。

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，收購智慧財產權研發支出為2,800萬美元，其中包括向合作方Adicet支付的2,000萬美元選擇加入費。 2021年全年，共有4,400萬美元的預付款未計入非GAAP研發費用，這些款項均已計入2021年第四季。

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.

銷售、一般及行政費用年增10%至3.89億美元，主要原因是安永（EYLEA）成長計畫的相關成本以及為支持公司擴張而增加的員工人數。商品和服務成本年增58%至1.98億美元，主要原因是Dupixent銷售額成長以及美國以外地區賽諾菲（Sanofi）Praluent商業供應量增加。

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

最後，2022 年第一季的實際稅率為 11.6%，而去年同期為 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.

接下來我們來看現金流和資產負債表。 2022年第一季，Regeneron公司產生20億美元的自由現金流，其中包括2021年第四季確認的美國政府支付的REGEN-COV銷售款項。截至2022年第一季末，該公司持有的現金及有價證券減去債務後為114億美元。

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.

我們持續推進資本配置優先事項。上個月，我們宣布達成協議，將以約2.5億美元的股權價值收購CheckMate Pharmaceuticals。本週早些時候，我們啟動了對CheckMate股份的要約收購，預計該交易將於2022年年中完成，但需獲得監管部門批准並滿足其他慣例成交條件。

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年第一季回購了價值3.52億美元的股票。我們將繼續伺機買入，在股價與其內在價值出現偏差時進行投資。

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，我將簡要介紹我們對2022年全年業績指引和展望的更新。我們先前已將全年研發投入指引調整為29億美元至31億美元。此次上調主要受下一代新冠抗體臨床生產成本的影響，其中大部分已計入第一季度，以及我們研發管線中其他項目的推進。此外，我們預計全年實際稅率將在12%至14%之間。有關我們最新全年業績指引的完整摘要，請參閱今天早些時候發布的新聞稿。

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，憑藉我們強大的財務實力，我們將繼續增加對研發的投入，這使得 Regeneron 能夠實現可持續的長期成長。

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

這樣，我就把電話轉回給瑞恩了。

Thank you, Bob.

謝謝你，鮑伯。

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.

吉吉，我們的發言到此結束。現在進入問答環節。由於排隊等候的聽眾超過20位，為了確保我們能夠回答盡可能多的問題，我們將對每位聽眾只回答一個問題，然後再回答下一位。

Gigi, please go ahead.

吉吉，請繼續。

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

（操作說明）我們的第一個問題來自 Piper Sandler 公司的 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.

我有個問題想問Marion，關於EYLEA以及它的競爭對手。我知道你們說過，目前市場和業務方面的回饋比較平淡，但羅氏對這款藥的市場反應卻截然不同，這著實令人驚訝。他們強調了股票市場的高度熱情，而且我知道大家都在熱議在獲得永久性J代碼後會發生什麼。

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?

我知道你們有很多策略可以運用，其中最重要的是推出高劑量版本的EYLEA。但你們能否談談回饋問題，以及它們在近期到中期內將如何影響你們的應對策略？我們未來該如何看待淨定價？

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，很高興能為你介紹市場狀況。首先，我想談談安永。正如我們今天報告的那樣，在競爭激烈的市場中，安永在各個適應症方面的表現都非常強勁。我們不僅獲得了遠超預期的市場份額，而且在各個適應症方面也取得了具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.

再次提醒，在農村市場，我們與安樂共同佔據了VEGF品類約50%的市場。而在品牌市場，我們佔了超過75%的品牌市佔率。

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.

我確實認為最好還是讓羅氏公司來評論他們新產品在市場上的接受度。我只想說，處方醫生和意見領袖們都非常重視EYLEA已證實的安全性、其療效，以及我們在適應症和市場使用方面所做的全面評估，這些都證明了EYLEA的可靠性。

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.

至於定價等其他相關事宜，我們通常不予置評。但我可以肯定地說，展望未來，我們看到安樂死展現出強大的領導地位，其在體驗、市場接受度和使用率方面都遙遙領先於同類產品。

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科里·卡西莫夫。

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?

關於EYLEA，我想進一步了解高劑量配方。假設結果如您預期，您認為這款產品在治療領域的潛在定位是什麼？它是否有可能全面取代您目前的劑量？或者您認為它主要會應用於某些特定市場領域？

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，目前我們需要等待臨床數據更加成熟，再來評估產品特性。當然，在進入上市準備階段時，我們會充分考慮產品特性與病患需求和市場機會的匹配度。因此，關於市場接受度的具體情況，我們還需要進一步討論。我們仍然保持樂觀。但當然，我們需要等待臨床數據更加成熟，產品特性也更加明確。

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 資本市場的 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?

如果您能詳細說明收購或擬收購Checkmate Pharmaceuticals的理由，我將不勝感激。在盡職調查過程中，有哪些數據特別引人注目，引起了您的興趣？您是否計劃將他們的資產與Libtayo結合使用，而不是像他們之前的試驗那樣與nivolumab或pembro結合使用？

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.

我確信－－是倫。我也相信喬治很樂意參與討論。但遺憾的是，由於我們剛發起收購要約，我們目前還沒有時間進行相關討論。我們期待著進行討論，前提是交易能夠如我們預期那樣在年中左右完成。

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

好吧，萊恩。好吧。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.

但由於我們無法回答這個問題，如果您重新排隊，我們會再來問您另一個問題。

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薩爾文·里希特。

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?

關於這些針對實體瘤下半年的初始雙特異性抗體資料集，您能否具體談談我們最初會看到什麼？以及您希望從這些數據集中看到哪些具有臨床意義的結果？

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.

正如我剛才所說，我們主要針對晚期、接受過大量預先治療的病人。我們希望能夠觀察到客觀的療效，而療效的數量和持續時間正是我們關注的重點。我們渴望看到大量持久的療效，證明每一種新型藥物都能真正改善晚期病人的病情。

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每個人帶來非常重要的機遇，無論是在晚期治療方面，還是在與早期患者進行邏輯結合方面。因此，他們每個人屆時都可能成為一個重要的項目，不僅在經濟方面，而且與其他相關機構合作也能產生顯著效益。

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

正如我所說，我們在所有這三個項目中都尋找的是具有持續時間的回饋。

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.

為了確保大家都能理解喬治剛才說的意思，我再補充一點：這類試劑似乎與其他抗癌藥物一樣，雖然最初是針對病情最嚴重、最難治的患者，但這類免疫試劑在早期患者中療效更佳。因此，如果能在晚期、接受過大量預處理的患者中發現療效，那將非常令人鼓舞。

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

下一個問題來自加拿大皇家銀行資本市場的布萊恩亞伯拉罕。

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?

恭喜所有的進展。您能否詳細談談增加 odronextamab 劑量後觀察到的安全優勢？我想，這與正在研發的其他雙特異性抗體，以及最終的 CAR-T 療法相比，意味著什麼？您又如何確信，在這個劑量下，odronextamab 能保持同樣強大的療效？

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。事實上，我們率先提出了雙特異性抗體的概念，因為我們是遞增劑量療法領域的早期拓荒者。我們自己的數據和其他研究者的數據都證實，當初始劑量較低，然後逐漸增加到最佳劑量時，可以降低嚴重副作用的發生率，尤其是細胞激素釋放症候群。

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.

我們最初的給藥方案其實很低，所以最初的給藥方案也是逐步遞增的。但是，在與FDA合作後，我們重新定義了逐步遞增的給藥方案，並制定了一個更漸進的方案。這個方案只是將達到最大劑量的時間延長了一周，而我們最終達到的劑量顯然是一樣的。

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.

我們想說的是，根據新劑量遞增方案的初步結果（我們預計未來某個時候會提供詳細數據），結果非常令人鼓舞。我們先前觀察到的顯著細胞激素釋放症候群發生率已經很低，現在看來似乎進一步降低，正如我之前所說，我們認為這種治療方案可以在門診環境中應用。

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，我們找到了一種安全性——看起來安全——的方案，可以在門診環境中使用，這非常令人鼓舞。而且，它在很短的時間內就能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巴克萊資本的卡特·古爾德。

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.

我有個問題。我想了解您是如何看待您在心血管領域的整體策略佈局的？我們最近聽到很多大型製藥和生技公司都在重新投入心血管領域。如果您梳理一下適應症和產品線，我認為您在心血管領域的研發管線非常廣泛。但您在這方面並沒有得到太多認可，而且您和Evkeeza的銷售額可能仍然只占公司總銷售額的一小部分。那麼，您認為心血管領域未來會成為Regeneron公司一個重要的商業領域嗎？我只是想更深入地了解您在這方面的雄心壯志。

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.

顯然，我們尚未完全發揮我們在細胞遺傳學方面的專業知識和能力，我們正在探索如何實現這一目標。其中一些方法可能需要我們重新考慮試劑和標靶的組合，希望您能聽到更多相關資訊。但我們承認，就目前而言，它並非我們近期業績的主要貢獻者。

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

我們的下一個問題來自 Baird 公司的 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?

這裡是盧克·赫爾曼，替布萊恩·斯科尼發言。能否再詳細談談5458？您對目前正在招募病患的II期研究能否支持提交上市申請有信心嗎？關於具體的上市時間表，以及您特別看好的合併用藥方案，您有什麼建議嗎？

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。就小樣本量而言，我們獲得了極具競爭力的緩解率，且緩解深度和持續時間都非常高。我們認為，對於這些晚期患者，如果我們能在正在進行的更大規模的II期註冊研究中複製這些結果，就足以支持註冊申請。我們持續觀察到非常可接受的安全性和耐受性。正如您所說，這只是整個專案的第一步。我們對聯合療法充滿信心，也對推進到更早期的治療方案感到非常興奮。

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.

就聯合用藥而言，正如我們之前討論過的，這非常合乎邏輯，而且臨床前數據也非常令人信服，即與所謂的共刺激雙特異性藥物聯合使用，這些藥物也能與同一骨髓瘤細胞上的靶點結合，但現在激活我們和其他人所說的[信號 2]，這將非常令人興奮，並且確實有可能增強反應性、加深反應性和延長持續時間。

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.

我們還有一系列下一代候選藥物，可以疊加到下一系列邏輯組合之上，這些組合都涉及這些共刺激分子。而且，正如Len已經提到的，我們認為，更早採用治療方案只會提高療效，增加獲得更持久療效的機會，甚至可以說，有可能治癒疾病。

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.

以上就是我們專案的基本概述。首先，我們將透過複製正在進行的註冊研究（可能包括二期臨床試驗）中獲得的數據，在晚期患者群體中獲得註冊。其次，我們將增加合併用藥方案，以增強療效、加深療效並延長療效持續時間。第三，我們將把治療方案擴展到更早的治療階段。

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?

這裡是布列塔尼，替泰勒發言。恭喜你們又一個季度業績斐然。接下來我要問一個多方面的問題，其中也包括與REGEN-COV雞尾酒療法相關的問題。對於正在進行的下一代候選藥物研究，你們預計何時會提交審批申請，以及未來的監管路徑會是怎樣的？另外，如果我們在進入地方性流行階段後，病例數仍然處於相對較低的時期，那麼關鍵性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。我們正在繼續與FDA討論監管路徑，包括如何獲得現有雞尾酒療法的全面批准（希望如此），以及下一代雞尾酒療法的監管路徑。這是一個持續進行的討論，可能會有所變化，支持該計畫的相關研究也可能會有所調整。因此，目前我們不打算討論任何細節。但這些問題都很好。

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.

毋庸置疑，當你還要考慮供應問題時，情況就變得更加複雜了。正如喬治所說，我們正在與監管機構討論授權需要哪些條件。但我們始終在追逐下一個變體，雖然我們可能擁有目前市場上最強大的端到端生產能力，但仍然需要知道針對哪種抗體生產哪種變體，以及如何持續追蹤這些變體，這仍然是一個相當複雜的問題。但我們致力於將單株抗體作為解決方案的重要組成部分。我認為它們可以成為解決方案的一部分，但這需要一些巧妙的科學方法。

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?

祝賀你們所有專案都取得了進展。關於 PHOTON 和 PULSAR 的結果，我有一個問題。多年來，我一直關注你們關於 EYLEA 的進展，你們的團隊在下一代藥物研發方面總體上是正確的，儘管這些研發未能取代 EYLEA 作為標準療法的地位。因此，我對你們關於 CANDELA 研究結果的評論以及它如何影響你們對 PHOTON 和 PULSAR 結果的解讀很感興趣。也就是說，你們團隊認為，對於那些能夠接受高劑量治療並延長至每 16 週一次的患者來說，最終的差異化療效究竟是什麼？這是否需要與 faricimab 研究的結果進行比較，才能使其成為市場上具有競爭力的藥物選擇或高劑量替代方案，以補充 EYLEA 的不足？

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.

而我猜想，之所以這麼說，是因為你們一直以來都認為，許多將 EYLEA 與按說明書用藥進行比較的研究其實並不公平。法瑞西單抗顯然使用了額外的負荷劑量。但在實際應用中，EYLEA 與其他任何藥物的治療效果其實都相當。

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?

所以我很想知道，您認為這些高劑量阿柏西普研究的背景分析，究竟該如何幫助我們確定，如果高劑量阿柏西普上市，哪些病人應該接受這種治療？

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.

顯然，這最終將由臨床醫生在查看所有數據後自行決定。但我認為，重要的考量因素仍然不僅包括療程（因為療程確實重要）、療效、療效管理，還包括安全性。我認為高劑量EYLEA的顯著優勢在於，從分子層面來看，無論是否出現免疫反應等問題，EYLEA都是非常成熟的藥物。如果我們能夠在保持相同安全性的前提下過渡到更高劑量，並延長療程，我認為這比採用一種安全性未經證實、但已有5000萬次注射驗證的新型分子作用機制更具吸引力。坦白說，我認為即使是FDA也會認為，改變同一分子的給藥方案與引入一種新分子是不同的。

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.

因此，我們無法預測，也不敢妄言臨床醫生在看到數據後會採取什麼行動，但我們強烈認為，如果沿用 EYLEA 的基礎，並且能夠獲得目前從小型 CANDELA 研究中獲得的預期安全性，以及能夠延長研究持續時間，那麼或許會促使我們更加關注實際數據。我認為這種過渡方式比使用新試劑的過渡方式更有效率。

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查理楊。

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?

我是Charlie Yang，替Matthew發言。我想跟進一下關於REGN5458這款BCMA雙特異性抗體。我的問題是，鑑於競爭對手的產品目前領先，並且可能在今年晚些時候獲得批准，他們已經在進行與DARZALEX等抗體組合的測試，我很好奇您對REGN5458的前景有何信心。能否也談談您對競爭格局以及不同應用場景下的商業機會的看法？

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，在這裡略微領先或落後其實意義不大。關鍵在於你的藥物本身的療效如何。當然，還有你有哪些合併用藥的機會。正如我們所說，如果我們能在可能具有關鍵意義的二期臨床試驗中重現我們在初步研究中觀察到的療效，那麼它將成為一種在療效方面極具競爭力的藥物，而這顯然才是真正重要的。

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.

但就合併用藥而言，我們相信我們擁有一些最有趣、最具顛覆性的潛在組合，例如與新型藥物（如共刺激雙特異性抗體）的組合，這與傳統藥物的組合截然不同。因此，它不僅能提升單藥療法在晚期治療中的療效，而且在早期治療中也能發揮同樣重要的作用，甚至更進一步，從而真正將療效提升到一個新的水平。

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，領先或落後一點並不像產出真正優質的數據那麼重要。我們認為，關鍵在於你是否能夠提出真正有趣且合乎邏輯的組合，這些組合能夠真正改變遊戲規則。我們相信我們擁有這樣的機會，這也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莫希特·班薩爾。

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?

太好了，謝謝您抽出時間。我有一個關於EYLEA，特別是高劑量EYLEA的問題。 George，我很想聽聽您對DME試驗設計的看法。看起來2毫克組的給藥方案是每個月一次，共5次，和說明書上寫的一樣，但8毫克組只有3次。您能解釋一下這種差異背後的原因嗎？這樣會不會讓高劑量EYLEA處於劣勢？

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。當然，正如Len所說，高劑量EYLEA的最終目標是在減少注射次數的同時，達到與低劑量EYLEA相同的療效和安全性（安全性至關重要）。坦白說，正如您所說，要用更少的注射次數達到PHOTON試驗的效果，難度確實比2毫克EYLEA更大。但這正是高劑量阿柏西普的目標。所以這確實具有挑戰性，但關鍵在於更高的劑量。這就是我們的目標，我想最終的數據會說明一切。

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。而且我認為我們可以排除這種可能性。當然，如果初始劑量過高，可能會影響療效的測定結果。但正如喬治所說，根據我們設計時的認知，我們對此持樂觀態度。

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

好的，謝謝。我想我們結束了。

Gigi, we conclude the call.

Gigi，通話結束了。

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。您可以斷開連線了。