雷傑納榮製藥 (REGN) 2025 Q4 法說會逐字稿

Welcome to the Regeneron Pharmaceuticals fourth-quarter 2025 earnings conference call. My name is Shannon, and I will be your operator for today's call. (Operator Instructions) Please note that this conference call is being recorded.

歡迎參加 Regeneron Pharmaceuticals 2025 年第四季財報電話會議。我叫香農，我將擔任您今天通話的接線生。（操作員說明）請注意，本次電話會議正在錄音。

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

現在我將把電話交給投資者關係高級副總裁瑞安·克羅。你可以開始了。

Thank you, Shannon. Good morning, good afternoon, and good evening to everyone listening around the world. Thank you for your interest in Regeneron and welcome to our fourth-quarter 2025 earnings conference call. An archive and transcript of this call will be available on the Regeneron Investor Relations website shortly after our call concludes.

謝謝你，香農。全世界的聽眾朋友們，早安、下午好、晚上好。感謝您對 Regeneron 的關注，歡迎參加我們 2025 年第四季財報電話會議。本次電話會議的錄音和文字記錄將在會議結束後不久發佈在 Regeneron 投資者關係網站上。

Joining me on today's call are Dr. Leonard Schleifer, Board, Co-Chair, Co-Founder, President, and Chief Executive Officer; Dr. George Yancopoulos, Board, Co-Chair, Co-Founder, President, and Chief Scientific Officer; Marion McCourt, Executive Vice President of Commercial; and Chris Fenimore, Executive Vice President and Chief Financial Officer.

今天與我一起參加電話會議的有：董事會聯席主席、聯合創始人、總裁兼首席執行官 Leonard Schleifer 博士；董事會聯席主席、聯合創始人、總裁兼首席科學官 George Yancopoulos 博士；商業執行副總裁 Marion McCourt；以及執行副總裁兼首席財務官 Chris Fenimore。

After our prepared remarks, the remaining time will be available for your Q&A. I would like to remind you that remarks made on today's call may include forward-looking statements about Regeneron. Such statements may include but are not limited to those related to Regeneron and its products and business, financial forecast and guidance, development programs, and related anticipated milestones, collaborations, finances, regulatory matters, payer coverage and reimbursement, intellectual property, pending litigation, and other proceedings and competition.

在我們發言完畢後，剩餘時間將留給各位提問。我想提醒各位，今天電話會議上發表的言論可能包含 Regeneron 的前瞻性陳述。此類聲明可能包括但不限於與 Regeneron 及其產品和業務、財務預測和指導、開發計劃和相關預期里程碑、合作、財務、監管事項、支付方覆蓋範圍和報銷、智慧財產權、未決訴訟和其他程序和競爭相關的聲明。

Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-K for the year ended December 31, 2025, which we plan to file with the SEC next week. Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events, or otherwise.

每項前瞻性聲明都存在風險和不確定性，可能導致實際結果和事件與該聲明中預測的結果和事件有重大差異。有關這些及其他重大風險的更完整描述，請參閱 Regeneron 向美國證券交易委員會提交的文件，包括截至 2025 年 12 月 31 日止年度的 10-K 表格，我們計劃在下周向美國證券交易委員會提交該表格。Regeneron不承擔任何更新任何前瞻性聲明的義務，無論是由於新資訊、未來事件或其他原因。

In addition, please note that GAAP and non-GAAP financial measures will be discussed on today's call. Information regarding our use of non-GAAP financial measures and a reconciliation of those measures to GAAP is available in our quarterly results press release and our corporate presentation, both of which can be found on the Regeneron Investor Relations website. Once our call concludes, the IR team will be available to answer any further questions.

此外，請注意，今天的電話會議將討論GAAP和非GAAP財務指標。有關我們使用非 GAAP 財務指標以及這些指標與 GAAP 的調節的信息，請參閱我們的季度業績新聞稿和公司演示文稿，這兩份文件均可在 Regeneron 投資者關係網站上找到。通話結束後，投資人關係團隊將隨時解答您的任何問題。

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

接下來，我將把電話交給我們的總裁兼執行長倫納德‧施萊弗博士。萊恩，你來吧。

Thanks, Ryan, and thanks to everyone for joining today's call. Regeneron capped 2025 was another solid quarter of commercial execution with fourth quarter total revenue up 3% year-over-year driven by double-digit net sales growth for three of our leading products. Compared to the fourth quarter of last year, global net product sales for Dupixent as reported by Sanofi, increased by 32% and Libtayo by 13% at constant exchange rates, while EYLEA HD in the United States grew by 66%.

謝謝瑞恩，也謝謝各位參加今天的電話會議。Regeneron 2025 年第四季商業執行穩健，總營收年增 3%，主要得益於我們三款領先產品的淨銷售額實現了兩位數成長。與去年第四季相比，賽諾菲報告稱，Dupixent 的全球淨產品銷售額按固定匯率計算增長了 32%，Libtayo 增長了 13%，而 EYLEA HD 在美國的增長率為 66%。

Global Dupixent net sales were $4.9 billion in the fourth quarter and $17.8 billion for the full year 2025. Dupixent is currently the most widely used innovative brand antibody medicine with more than 1.4 million patients on therapy globally. Now approved in eight indications, most of which remain significantly underpenetrated, Dupixent is well positioned for future growth.

Dupixent 第四季全球淨銷售額為 49 億美元，2025 年全年淨銷售額為 178 億美元。Dupixent是目前使用最廣泛的創新品牌抗體藥物，全球有超過140萬名患者正在接受治療。目前，Dupixent 已獲準用於八種適應症，其中大多數適應症的滲透率仍然很低，因此 Dupixent 為未來的成長奠定了良好的基礎。

Global Libtayo net product sales were $425 million in the fourth quarter and $1.45 billion for the full year 2025. In the US, Libtayo continues to be the market-leading immunotherapy for advanced non-melanoma skin cancers. Following FDA and EC approvals of Libtayo for adjuvant CSCC in the fourth quarter, we are making great progress launching this potential blockbuster opportunity, with this indication expected to be a significant growth driver for Libtayo in 2026 and beyond.

Libtayo 第四季全球淨產品銷售額為 4.25 億美元，2025 年全年淨產品銷售額為 14.5 億美元。在美國，Libtayo 仍然是治療晚期非黑色素瘤皮膚癌的市場領先的免疫療法。繼 FDA 和 EC 在第四季度批准 Libtayo 用於輔助治療 CSCC 之後，我們在推出這一潛在的重磅藥物方面取得了巨大進展，預計該適應症將成為 Libtayo 在 2026 年及以後的重要增長動力。

Libtayo also continues to build share in advanced non-small cell lung cancer, where in the US, it is now the second most prescribed immunotherapy in the first line setting with new patient market share in this setting greater than Opdivo, Tecentriq, and Imfinzi combined. EYLEA HD net product sales in the United States were $506 million in the fourth quarter up 66% and $1.6 billion for the full year 2025 of 36% despite continued patient co-pay affordability issues that have dampened branded anti-VEGF category growth.

Libtayo 在晚期非小細胞肺癌領域也持續擴大市場份額，在美國，它現在是第一線治療中處方量第二大的免疫療法，在該領域的新患者市場份額超過了 Opdivo、Tecentriq 和 Imfinzi 的總和。儘管患者自付費用問題持續存在，抑制了品牌抗 VEGF 藥物類別的成長，但 EYLEA HD 在美國的第四季淨產品銷售額為 5.06 億美元，年成長 66%，預計到 2025 年全年銷售額將達到 16 億美元，年成長 36%。

In November, the FDA approved LHD for macular edema following retinal vein occlusion or RVO, and monthly dosing across all approved indications, further strengthening the EYLEA HD compelled profile. Our FDA submission seeking approval of the EYLEA HD prefilled syringe using a new manufacturer has been accepted for review, a standard pre-license inspection has been scheduled, and the decision on our filing is expected in late April.

11 月，FDA 批准 LHD 用於治療視網膜靜脈阻塞或 RVO 引起的黃斑水腫，並批准其在所有已批准的適應症中每月給藥一次，進一步加強了 EYLEA HD 的強制性地位。我們向 FDA 提交的關於使用新製造商生產的 EYLEA HD 預填充注射器的審批申請已被接受審查，標準的上市前檢查已經安排，預計將在 4 月下旬做出關於我們申請的決定。

In addition, as a backup, Catalent Indiana continues to work with the FDA to resolve findings from a previous inspection. We continue to believe that all three of these product enhancements are key to fully unlocking EYLEA's HD commercial potential. While we anticipate continued growth in EYLEA HD this year, EYLEA 2 milligrams will continue to be under competitive pressure, which is expected to intensify in the second half of 2026 as multiple biosimilar products are launched in the United States.

此外，作為備用方案，Catalent Indiana 繼續與 FDA 合作，解決先前檢查中發現的問題。我們仍然相信，這三項產品改進是充分釋放安樂高清產品商業潛力的關鍵。雖然我們預計今年 EYLEA HD 將繼續成長，但 EYLEA 2 毫克將繼續面臨競爭壓力，預計隨著多種生物相似藥在美國上市，這種壓力將在 2026 年下半年加劇。

Regarding patient affordability, we are pleased that we matched a $60 million donation to the good days retinal vascular and neovascular disease fund in the fourth quarter. Today, we reiterated our commitment to helping patients afford their medicines by extending our matching program through the end of this year up to $200 million.

關於患者負擔能力，我們很高興在第四季度向「美好時光」視網膜血管和新生血管疾病基金捐贈了 6000 萬美元。今天，我們重申了我們幫助患者負擔得起藥品費用的承諾，將我們的配​​捐計劃延長至今年年底，總額高達 2 億美元。

Turning now to our negotiations with the United States government regarding efforts to reduce drug costs for American patients. We are actively engaging in constructive discussions with the Centers for Medicare and Medicaid services and other federal agencies, and we anticipate reaching agreement in alliance with the framework previously established by other companies.

現在我們來談談與美國政府就降低美國病患藥品成本所做的談判。我們正在積極與醫療保險和醫療補助服務中心以及其他聯邦機構進行建設性討論，我們預計會與其他公司先前建立的框架達成協議。

We remain optimistic about striking a deal with the administration to achieve our shared goals, ensuring timely and affordable access to groundbreaking medical advancements for American patients, maintaining the United States' leadership in biotechnology, innovation, and manufacturing and addressing the long-standing imbalance in the distribution of costs for medical innovation, which has historically placed a disproportionate burden on American patients.

我們仍然樂觀地認為，我們將與政府達成協議，實現我們的共同目標，確保美國患者及時、負擔得起地獲得突破性的醫療進步，保持美國在生物技術、創新和製造領域的領先地位，並解決醫療創新成本分配長期不平衡的問題，這個問題歷來給美國患者帶來了不成比例的負擔。

Finally, looking ahead to the next 12 months, Regeneron has several key objectives that I'd like to share. First, we anticipate at least four FDA approvals, including three for new molecular entities across three distinct modalities plus approval for the EYLEA HD prefilled syringe as well as several additional regulatory submissions.

最後，展望未來 12 個月，Regeneron 有幾個關鍵目標想和大家分享。首先，我們預計至少會有四項 FDA 批准，其中包括三種不同治療方式的新分子實體的批准，以及 EYLEA HD 預充式註射器的批准，此外還有幾項其他監管申請。

We expect registration-enabling data for multiple programs, including fianlimab, our LAG-3 antibody, in combination with Libtayo and advanced melanoma, as well as a combination of cemdisiran and pozelimab in PNH.

我們期待獲得多個項目的註冊支持數據，包括我們的 LAG-3 抗體 fianlimab 與 Libtayo 聯合用於治療晚期黑色素瘤，以及 cemdisiran 和 pozelimab 聯合用於治療 PNH。

In addition to the ongoing clinical studies in key areas such as myeloma, anticoagulation, and complement-mediated diseases, 2026 will be an important clinical development execution year as we anticipate initiating 18 additional Phase 3 studies, with cumulative target enrollment of approximately 35,000 patients over multiple years, setting the foundation for Regeneron's next wave of potential blockbuster products.

除了正在進行的骨髓瘤、抗凝血和補體介導疾病等關鍵領域的臨床研究外，2026 年將是重要的臨床開發執行年，因為我們預計將啟動 18 項額外的 3 期研究，目標是在多年內累計招募約 35,000 名患者，為 Regeneron 的下一波潛在重磅產品奠定基礎。

We also plan to begin clinical development of at least three first-in-class antibodies that address novel targets, of which two were discovered and validated by the Regeneron Genetics Center, as well as our long-acting IL-13 antibody in atopic dermatitis. We expect strong commercial execution to continue, maximizing the potential of our leading brands across key therapeutic areas.

我們也計劃開始至少三種針對新標靶的首創抗體的臨床開發，其中兩種是由 Regeneron 遺傳學中心發現和驗證的，還有我們用於治療異位性皮膚炎的長效 IL-13 抗體。我們預計強勁的商業執行力將持續維持，最大限度地發揮我們領先品牌在關鍵治療領域的潛力。

And finally, we plan to continue to prudently deploy capital through share repurchases, dividends, and complementary business development, all with the goal of driving long-term shareholder value. Obviously, a busy, and a fast and ambitious year ahead, one that I'm particularly energized and excited to evolve. We look forward to reporting our progress on these goals as we move through the year..

最後，我們計劃繼續審慎地運用資本，透過股票回購、分紅和配套業務發展來實現長期股東價值。顯然，未來一年將會非常忙碌、節奏很快且充滿雄心壯志，我對此充滿熱情，也十分興奮，期待著在這一年中取得進步。我們期待在今年餘下的時間向大家報告我們在實現這些目標方面取得的進展。

With that, I'll turn the call over to George.

這樣，我就把電話交給喬治了。

Thanks, Len. Earlier this month at the JPMorgan conference, we highlighted the breadth and depth of our pipeline, which is expected to generate clinical data over the next few years spanning oncology, hematology, complement mediated diseases, anticoagulation, and obesity as well as in other areas.

謝謝你，Len。本月初在摩根大通會議上，我們重點介紹了我們產品線的廣度和深度，預計未來幾年內，該產品線將產生涵蓋腫瘤學、血液學、補體介導疾病、抗凝血、肥胖症以及其他領域的臨床數據。

In 2026, we plan to build on our established leadership in ophthalmology as well as immunology information while advancing key late-stage programs. Starting with ophthalmology, EYLEA HD was recently approved by the FDA for monthly dosing and for the treatment of RVO, further strengthening its clinical profile. Data supporting these approvals will be presented at the upcoming Angiogenesis meeting, further highlighting the efficacy, safety, and durability of EYLEA HD, along with dosing flexibility designed to support more personalized patient care.

2026年，我們計劃鞏固我們在眼科學和免疫學資訊領域的領先地位，同時推進關鍵的後期專案。從眼科領域開始，EYLEA HD 最近獲得了 FDA 的批准，可每月給藥一次，用於治療視網膜靜脈阻塞 (RVO)，進一步加強了其臨床療效。支持這些批准的數據將在即將召開的血管生成會議上公佈，進一步強調 EYLEA HD 的療效、安全性和持久性，以及旨在支持更個性化患者護理的劑量靈活性。

In terms of our ophthalmology pipeline, for our C5 program for geographic atrophy, we expect interim data from our Phase 3 study in the second half of 2026. We are currently evaluating our C5 siRNA, cemdisiran, as monotherapy and also with pozelimab, our potentially best-in-class C5 antibody, with the goal of providing a systemic treatment that avoids the safety issues from repeated intravitreal injections associated with currently approved GA therapies. In case intravitreal delivery is required to adequately treat this disease, we've also begun clinical development of an intravitreal formulation of pozelimab to evaluate local C5 inhibition for appropriate patients.

就我們的眼科產品線而言，針對我們治療地圖狀萎縮的 C5 項目，我們預計將在 2026 年下半年獲得 3 期研究的中期數據。我們目前正在評估我們的 C5 siRNA cemdisiran 作為單藥療法以及與我們潛在的同類最佳 C5 抗體 pozelimab 聯合使用的效果，目標是提供一種全身治療方案，避免目前已獲批准的 GA 療法因重複玻璃體內註射而帶來的安全問題。如果需要玻璃體內給藥才能充分治療這種疾病，我們也已開始對 pozelimab 的玻璃體內製劑進行臨床開發，以評估局部 C5 抑制對合適患者的療效。

Beyond GA and ophthalmology, we have initiated a study of a novel intravitreally delivered T-cell receptor-blocking antibody for non-infectious uveitis, a disease generally driven by autoimmune T-cells. This advance was made possible by our unique antibody capabilities, as we are not aware of any other company that's been able to generate such an antibody. This year, we also plan to initiate clinical development for a long-acting antibody targeting a novel genetically validated target for glaucoma, along with a long-acting antibody that aims to treat thyroid eye disease and Graves' disease.

除了 GA 和眼科之外，我們還啟動了一項針對非感染性葡萄膜炎（一種通常由自體免疫性 T 細胞驅動的疾病）的新型玻璃體內注射 T 細胞受體阻斷抗體的研究。這項進展得益於我們獨特的抗體研發能力，據我們所知，目前還沒有其他公司能夠生產出這樣的抗體。今年，我們還計劃啟動針對一種新型基因驗證的青光眼標靶的長效抗體的臨床開發，以及一種旨在治療甲狀腺眼疾和格雷夫茲病的長效抗體的臨床開發。

Moving to immunology and inflammation, we are committed to strengthening our leadership by advancing several next-generation therapeutic approaches. As we first revealed at the JPMorgan conference, in addition to exploring longer dosing intervals for Dupixent, we are progressing VelocImmune-derived, fully human, long-acting antibodies with enhanced binding properties that target the IL-4 receptor alpha, the same target as Dupixent, as well as antibodies targeting IL-13, IL-4, and a bispecific antibody targeting both IL-4 and IL-13. All of these approaches are designed to enable extended dosing.

在免疫學和發炎領域，我們致力於透過推進幾種下一代治療方法來鞏固我們的領先地位。正如我們在摩根大通會議上首次透露的那樣，除了探索延長 Dupixent 的給藥間隔外，我們還在推進 VelocImmune 衍生的全人源長效抗體的研發，這些抗體具有增強的結合特性，靶向 IL-4 受體 α（與 Dupixent 相同的靶點），以及靶向 IL-13、靶向 IL-4 受體 α（與 Dupixent 相同的靶點），以及靶向 IL-13、2IL-4 的抗體和靶向 IL-4 的雙抗體-13、 IL-4 和 IL-13 的雙抗體-4 的靶向 IL-4。所有這些方法都是為了實現延長給藥時間而設計的。

Our long-acting IL-13 antibody is expected to enter the clinic in the coming months, embarking on an expedited development plan in atopic dermatitis that we believe will enable us to remain competitive as other industry players are pursuing related approaches.

我們的長效 IL-13 抗體預計將在未來幾個月內進入臨床試驗，我們將加快開發治療異位性皮膚炎的計劃，我們相信這將使我們能夠在其他行業參與者尋求相關方法時保持競爭力。

Our other long-acting antibodies are expected to enter the clinic by 2027, each with a custom development plan. At the same time, our Regeneron Genetics Center has utilized its large-scale genetics approaches to identify several exciting new immunology and inflammation targets.

我們其他長效抗體預計將於 2027 年進入臨床試驗階段，每種抗體都有客製化的開發計畫。同時，我們的 Regeneron 遺傳學中心利用其大規模遺傳學方法，發現了幾個令人興奮的新的免疫學和發炎目標。

Similar to Dupixent, we believe these may represent future pipeline and product opportunities. The first of these antibodies is expected to enter clinical development in the first half of this year. After initially evaluating healthy volunteers, we plan to rapidly advance this candidate to establish proof of concept in several genetically linked diseases such as lupus, Sjögren's, and primary biliary cholangitis.

與 Dupixent 類似，我們認為這些可能代表未來的研發管線和產品機會。預計首批此類抗體將於今年上半年進入臨床開發階段。在初步評估健康志願者之後，我們計劃迅速推進該候選藥物的研發，以在幾種與基因相關的疾病（如狼瘡、乾燥綜合徵和原發性膽汁性膽管炎）中建立概念驗證。

Turning now to allergy. Our initial cat and birch Phase 3 study demonstrated that allergen-specific monoclonal antibody cocktails can meaningfully address ocular endpoints, adding to earlier data that showed significant reductions in nasal, respiratory, and skin endpoints. These Phase 3 data from the cat and birch programs will be presented at the upcoming AAAAI conference. We anticipate initiating the confirmatory Phase 3 study for cat allergy in the first half of the year, while the confirmatory Phase 3 study for birch allergy is already underway.

接下來我們來談談過敏症。我們最初的貓和樺樹 3 期研究表明，過敏原特異性單株抗體混合物可以有效改善眼部終點，進一步補充了早期數據顯示的鼻部、呼吸道和皮膚終點顯著減少的情況。貓和樺樹計畫的這些第三階段數據將在即將舉行的 AAAAI 會議上公佈。我們預計今年上半年啟動貓過敏的確認性 3 期研究，而樺樹過敏的確認性 3 期研究已經開始。

We are also advancing an innovative strategy with the goal of eliminating all IgE-mediated allergies. Our initial clinical effort is in patients suffering from severe food allergies, involving transient linvoseltamab treatment followed by long-term Dupixent maintenance. This approach demonstrated proof of principle, with the first four treated patients all achieving over 90% sustained IgE reductions.

我們也在推動一項創新策略，目標是消除所有 IgE 介導的過敏症。我們最初的臨床研究對像是患有嚴重食物過敏的患者，包括短暫的 linvoseltamab 治療，然後是長期的 Dupixent 維持治療。這種方法證明了其原理，前四名接受治療的患者均實現了超過 90% 的持續 IgE 降低。

These results validate our approach of first removing IgE-producing plasma cells and then preventing their return. Building on this, we are developing next-generation agents specifically targeting IgE-producing cells, with the first expected to enter clinical development over the next year for potentially more rapid and broader allergy applications.

這些結果驗證了我們先去除產生 IgE 的漿細胞，然後防止其再生的方法。在此基礎上，我們正​​在開發專門針對產生 IgE 的細胞的下一代藥物，預計第一個藥物將在明年進入臨床開發階段，並有望實現更快速、更廣泛的過敏治療應用。

On to oncology and fianlimab, our LAG-3 antibody combination with Libtayo. Our pivotal study in first-line metastatic melanoma remains on track to read out in the first half of this year. Early clinical data from our first in-human study across multiple advanced melanoma cohorts suggested a potentially differentiated investment class profile. Also, in the first half of this year, we're expecting an interim analysis for our study in adjuvant melanoma, as well as Phase 2 data in advanced non-small cell lung cancer, a more speculative setting in which clinical validation has not yet been established for LAG-3 and PD-1 combinations.

接下來是腫瘤學和fianlimab，我們的LAG-3抗體與Libtayo的組合。我們針對第一線轉移性黑色素瘤的關鍵性研究仍按計畫進行，預計今年上半年公佈結果。我們首次針對多個晚期黑色素瘤患者群體進行的人體研究的早期臨床數據顯示，可能存在差異化的投資類別特徵。此外，今年上半年，我們預計將發表輔助黑色素瘤研究的中期分析結果，以及晚期非小細胞肺癌的 2 期數據。晚期非小細胞肺癌是一個更具推測性的領域，LAG-3 和 PD-1 聯合療法的臨床驗證尚未在該領域得到證實。

Moving to linvoseltamab, our BCMAxCD3 bispecific, is establishing a new benchmark in multiple myeloma. In late-line disease, and with the caveat of cross-trial comparisons, linvoseltamab has demonstrated nearly double the complete response rate compared to other BCMAxCD3 bispecifics at similar follow-up times, with lower rates of cytokine release syndrome, shorter hospitalization requirements, and more convenient dosing intervals.

轉向使用我們的 BCMAxCD3 雙特異性抗體 linvoseltamab，正在為多發性骨髓瘤樹立新的標竿。在晚期疾病治療中，考慮到跨試驗比較的局限性，linvoseltamab 在相似的隨訪時間內顯示出比其他 BCMAxCD3 雙特異性抗體高出近一倍的完全緩解率，同時細胞因子釋放綜合徵的發生率更低，住院需求更短，給藥間隔更方便。

Building on its remarkable monotherapy activity across multiple lines of therapy, we are undertaking an ambitious development plan to simplify the existing myeloma treatment paradigm, which currently relies on highly complex, intense, and burdensome triple and quad drug combinations by exploring linvoseltamab monotherapy as well as in simple combinations in early-line settings.

基於其在多線治療中卓越的單藥治療活性，我們正在進行一項雄心勃勃的開發計劃，旨在簡化現有的多發性骨髓瘤治療模式（目前依賴於高度複雜、強度高且負擔沉重的三聯和四聯藥物組合），通過探索 linvoseltamab 單藥治療以及在早期治療中的簡單組合來簡化該模式。

In our Phase 2 study in newly diagnosed multiple myeloma, all nine evaluable patients treated with linvoseltamab monotherapy at the planned Phase 3 dose achieved MRD negativity, an endpoint the FDA recently endorsed as a registrational enabling for this malignant disease. Even more compelling are the early signals in myeloma precursor and related settings.

在我們針對新診斷的多發性骨髓瘤患者進行的 2 期研究中，所有 9 名接受計劃的 3 期劑量 linvoseltamab 單藥治療的可評估患者均達到了 MRD 陰性，這是 FDA 最近認可的該惡性疾病的註冊終點。更引人注目的是骨髓瘤前驅期及相關疾病的早期訊號。

For example, in evaluable patients with high-risk smoldering myeloma, linvoseltamab once again achieved 100% MRD negative in all 12 evaluated patients, whereas the standard of care, daratumumab, achieved less than 10% complete response. Similarly, in second-line patients with light chain amyloidosis, linvoseltamab monotherapy normalized abnormal light chain levels in approximately two weeks, whereas in a separate study, a daratumumab-containing quad combo regimen took approximately five months to approach these levels in first-line patients.

例如，在可評估的高風險冒煙型骨髓瘤患者中，linvoseltamab 再次在所有 12 名接受評估的患者中實現了 100% 的 MRD 陰性，而標準療法 daratumumab 的完全緩解率不到 10%。同樣，在二線輕鏈澱粉樣變性患者中，linvoseltamab 單藥治療在大約兩週內使異常輕鏈水平恢復正常，而在另一項研究中，含 daratumumab 的四聯療法在一線患者中大約需要五個月才能達到這些水平。

Both of these promising results could herald market advances to existing standard of care, which can involve complex and toxic multi-drug combinations. With four pivotal studies underway and four more initiating by the middle of this year, we are rapidly advancing our linvoseltamab development program with the hopes of transforming the myeloma treatment paradigm and ultimately preventing progression to malignant disease.

這兩項令人鼓舞的結果可能預示著現有標準療法的市場進步，而現有標準療法可能涉及複雜且有毒的多藥組合。目前，我們正在進行四項關鍵研究，並計劃在今年年中啟動另外四項研究，我們正在快速推進 linvoseltamab 的開發計劃，希望能夠改變多發性骨髓瘤的治療模式，並最終阻止其發展為惡性疾病。

On to complement-mediated diseases, our C5 program consists of customized approaches to treat different diseases, which require different levels of target inhibition to maximize efficacy for each condition. I previously summarized above our C5 efforts in geographic atrophy.

對於補體介導的疾病，我們的 C5 計劃包括針對不同疾病的客製化治療方法，這些疾病需要不同程度的標靶抑制才能最大限度地提高每種疾病的療效。我之前已在上文中總結了我們在地理萎縮方面所做的 C5 工作。

In our pivotal study for generalized myasthenia gravis, we showed that cemdisiran alone achieved differentiated efficacy and convenience with every three-month subcutaneous dosing, delivering a potentially best-in-class profile with a placebo-adjusted improvement in the myasthenia gravis activities of daily living score of 2.3 points at 24 weeks, the primary endpoint of the study, and the best result among C5 inhibitors to date based on cross-trial comparisons. We remain on track to submit our US regulatory application in the first quarter, with potential approval anticipated later this year or early next year.

在我們針對全身性重症肌無力的關鍵研究中，我們證明，每三個月皮下注射一次西地西蘭即可實現差異化的療效和便利性，在 24 週時，重症肌無力日常生活活動評分較安慰劑組提高了 2.3 分，這是該研究的主要終點，並且根據跨試驗比較，這是迄今為止 C5 抑製劑中的最佳結果，具有潛在的同類療效。我們仍按計劃在第一季提交美國監管申請，預計今年稍後或明年年初獲得批准。

In paroxysmal nocturnal hemoglobinuria, or PNH, where our Phase 3 lead-in data showed the combination of cemdisiran and eculizumab was necessary to achieve potentially best-in-class disease control, with 96% of patients controlled in the pivotal trial lead-in cohort, and with the ability to rapidly rescue patients previously treated with ravulizumab who had not been well controlled. These results once again have the potential to deliver a best-in-class profile, with pivotal data expected late this year or early next year, positioning this combination of C5 complement inhibitors as a new standard of care for PNH.

在陣發性睡眠性血紅蛋白尿症（PNH）中，我們的 3 期導入數據顯示，cemdisiran 和 eculizumab 的聯合治療對於實現同類最佳的疾病控制至關重要，在關鍵性試驗導入隊列中，96% 的患者病情得到控制，並且能夠快速挽救先前接受 ravulizumab 治療但病情控制不佳的患者。這些結果再次展現出成為同類最佳藥物的潛力，關鍵數據預計將於今年稍後或明年年初公佈，這將使這種 C5 補體抑制劑組合成為 PNH 的新標準療法。

Moving to anticoagulation, clot prevention remains a critical unmet need, since less than half of eligible patients receive anticoagulant therapy, primarily due to concerns about their bleeding risk. To address this, we are developing two complementary Factor XI antibodies, one optimized for maximal antithrombotic activity and the other designed to further reduce bleeding risk, enabling a tailored approach based on individual patients' benefit-risk profile.

就抗凝血治療而言，血栓預防仍然是一個亟待解決的關鍵問題，因為只有不到一半符合條件的患者接受了抗凝血治療，這主要是由於擔心出血風險。為了解決這個問題，我們正在開發兩種互補的因子XI抗體，一種針對最大抗血栓活性進行了優化，另一種旨在進一步降低出血風險，從而能夠根據個別患者的獲益風險比進行量身定制的治療方案。

Initial clinical data support this strategy, showing impressive efficacy and a favorable bleeding profile compared to current standards of care. Pivotal studies are already underway in prevention of post-surgical venous thromboembolism, or VTE, with pivotal studies of cancer-associated VTE prevention, catheter-associated thrombosis, stroke prevention in patients with atrial fibrillation, and peripheral artery disease, all expected to initiate this year.

初步臨床數據支持此策略，與目前的標準治療相比，顯示出顯著的療效和良好的出血情況。預防術後靜脈血栓栓塞症（VTE）的關鍵研究已經展開，而癌症相關 VTE 預防、導管相關血栓形成、房顫患者中風預防以及外周動脈疾病的關鍵研究預計都將在今年啟動。

Moving to obesity, we continue to pursue a differentiated strategy that includes olorelapide, our in-licensed GLP-GIP agonist, entering pivotal monotherapy studies in 2026, as well as a co-formulation of olorelapide with PRALUENT, our antibody to PCSK9. Since current GLP agonists do not meaningfully lower LDL cholesterol, this co-formulated combination is designed to treat the large population of people living with obesity who also suffer from hyperlipidemia, with a single, convenient, and similarly affordable once-weekly subcutaneous injection, analogous to the currently approved GLPs.

轉向肥胖症，我們繼續推行差異化策略，其中包括我們引進的 GLP-GIP 激動劑奧洛瑞拉派，該藥物將於 2026 年進入關鍵性單藥治療研究，以及奧洛瑞拉派與我們針對 PCSK9 的抗體 PRALUENT 的聯合製劑。由於目前的 GLP 激動劑無法顯著降低 LDL 膽固醇，因此這種複方製劑旨在治療大量同時患有肥胖症和高脂血症的人群，只需每週一次皮下注射，即可方便快捷地進行治療，其價格與目前已批准的 GLP 類似。

Moreover, imagine if someone had invented a new GLP that, in addition to delivering profound weight loss, could also lower bad cholesterol by 50% to 60%. It would create an important and differentiated opportunity for the many obese patients simultaneously suffering from hyperlipidemia with elevated cardiovascular risk. Our clinical program for this novel combination that we believe can deliver these same dual benefits is expected to begin later this year.

此外，想像一下，如果有人發明了一種新的 GLP，除了能顯著減輕體重外，還能降低 50% 到 60% 的壞膽固醇。這將為許多同時患有高血脂症和心血管疾病風險升高的肥胖患者創造一個重要且獨特的機會。我們相信，這種新型組合療法能夠帶來相同的雙重益處，我們的臨床試驗計畫預計將於今年稍後啟動。

Before I turn the call over to Mary, I would like to quickly address a couple of additional developments in our pipeline. In rare diseases, our DB-OTO gene therapy continues to produce transformative outcomes, with meaningful hearing gains in 11 of the 12 treated children born with profound genetic deafness. This program was selected as the first new molecular entity to receive the FDA Commissioner's National Priority Voucher Designation, and we are awaiting a regulatory decision in the first half of this year.

在將電話交給瑪麗之前，我想快速地談談我們專案進度中的幾個其他方面。在罕見疾病領域，我們的 DB-OTO 基因療法持續取得變革性成果，在接受治療的 12 名患有嚴重遺傳性耳聾的兒童中，有 11 名兒童的聽力得到了顯著改善。該計畫被選為首個獲得美國食品藥物管理局局長國家優先憑證認定的新分子實體，我們正在等待今年上半年的監管決定。

In fibrodysplasia ossificans progressiva, or FOP, a debilitating disease in which the soft tissues of the body are progressively replaced with abnormal bone, our garetosmab program demonstrated a more than 99% reduction in abnormal bone formation at 56 weeks, an unprecedented result, and we are awaiting on regulatory decisions in the US and EU in the second half of this year.

在進行性骨化性纖維發育不良症（FOP）這種使身體軟組織逐漸被異常骨骼取代的衰弱性疾病中，我們的 garetosmab 計畫在 56 週時顯示出異常骨骼形成減少超過 99%，這是一個前所未有的結果，我們正在等待美國和歐盟在今年下半年做出監管決定。

Our commitment and dedication to these types of rare diseases, particularly those that affect children, not only speak to the heart and soul of Regeneron but have also proven to pave the way for broader opportunities in the future, as we would hope would be the case here.

我們對這類罕見疾病，特別是影響兒童的罕見疾病的承諾和奉獻，不僅體現了 Regeneron 的核心價值觀，而且也已證明能夠為未來帶來更廣泛的機遇，我們希望這次也能如此。

In summary, our scientific and clinical momentum continues to accelerate across the R&D enterprise with multiple pivotal readouts, regulatory milestones, and first-in-class programs advancing in 2026. I have never been more excited about the breadth, depth, and potential impact of our pipeline.

總而言之，我們的科學和臨床發展勢頭在整個研發領域持續加速，多個關鍵性結果、監管里程碑和首創項目將在 2026 年取得進展。我從未像現在這樣對我們產品線的廣度、深度和潛在影響感到如此興奮。

With that, let me turn it over to Marion.

接下來，我將把麥克風交給瑪莉安。

Thank you, George. The fourth quarter delivered a strong finish 2025, completing a successful year across our commercial portfolio, our market-leading brands, EYLEA HD, Dupixent, and Libtayo continue to deliver sustainable growth based on their clinical profile as well as our ability to execute effectively in competitive markets.

謝謝你，喬治。第四季為 2025 年畫上了圓滿的句號，我們的商業組合也取得了成功，我們市場領先的品牌 EYLEA HD、Dupixent 和 Libtayo 繼續保持可持續增長，這得益於它們的臨床表現以及我們在競爭激烈的市場中有效執行的能力。

In 2025, we expanded use of our existing brands and successfully launched new medicines and indications across multiple therapeutic areas and geographies. We begin 2026 well positioned to advance our portfolio and are excited by upcoming opportunities to change the lives of even more patients.

2025年，我們擴大了現有品牌的使用範圍，並在多個治療領域和地區成功推出了新藥和新適應症。2026 年伊始，我們已做好充分準備推進產品組合，並對即將到來的機會感到興奮，這些機會將改變更多患者的生活。

Starting with our retinal franchise EYLEA HD and EYLEA, which delivered combined US net sales of $1.1 billion in the fourth quarter. EYLEA HD net sales reached $506 million, representing 18% sequential growth.

首先是我們的視網膜產品線 EYLEA HD 和 EYLEA，它們在第四季度為美國帶來了 11 億美元的淨銷售額。EYLEA HD淨銷售額達5.06億美元，較上季成長18%。

Performance was driven by a 10% increase in physician demand compared to the third quarter, highlighting EYLEA HD's strong clinical profile and commercial momentum despite a 7% sequential decline in the overall anti-VEGF category. This fourth quarter dynamic is typical for the anti-VEGF category.

與第三季相比，醫生需求成長了 10%，推動了業績成長，這凸顯了 EYLEA HD 強大的臨床表現和商業勢頭，儘管抗 VEGF 類別整體環比下降了 7%。第四季的這種動態是抗 VEGF 類別的典型特徵。

For full year 2025, the category maintained approximately 5% growth versus 2024, while the innovative branded segment, which excludes Avastin and biosimilars declined by approximately 12%. Importantly, EYLEA HD represents a growing proportion of Regeneron's total anti-VEGF franchise now contributing nearly half of total net sales.

2025 年全年，該類別與 2024 年相比保持了約 5% 的成長，而不包括 Avastin 和生物相似藥的創新品牌細分市場則下降了約 12%。值得注意的是，EYLEA HD 在 Regeneron 的抗 VEGF 產品線中所佔比例越來越大，目前貢獻了近一半的淨銷售額。

Following recent label enhancements to include monthly doses and retinal vein occlusion, EYLEA HD now has the broadest label and greatest dosing flexibility of any anti-VEGF medicine. Physicians were eagerly awaiting both label enhancements, and we are seeing positive early launch signals in our efforts to get this important medicine to even more patients.

經過最近的標籤改進，包括每月一次的給藥方案和視網膜靜脈阻塞，EYLEA HD 現在擁有所有抗 VEGF 藥物中最廣泛的標籤和最大的劑量靈活性。醫生們一直熱切期盼著這兩項標籤改進，而我們也看到了積極的早期上市跡象，這有助於我們將這種重要的藥物帶給更多的患者。

The combination of this new dosing flexibility with EYLEA HD's demonstrated durability further strengthens its position in the anti-VEGF retinal category. New real-world market data shows that on average, patients with ongoing anti-VEGF therapy who switched to EYLEA HD, we're able to extend their treatment duration by almost four weeks. This underscores EYLEA HD's durability profile in addition to its well-established efficacy and safety. We look forward to the potential FDA approval of our prefilled syringe, which if approved, will provide additional convenience for retina specialists and further enhance EYLEA HD's profile.

EYLEA HD 的新型給藥靈活性與已證實的持久性相結合，進一步鞏固了其在抗 VEGF 視網膜藥物領域的地位。最新的真實世界市場數據顯示，平均而言，正在接受抗 VEGF 治療的患者改用 EYLEA HD 後，治療持續時間可延長近四周。這不僅凸顯了EYLEA HD的持久耐用性，也證明了其卓越的功效和安全性。我們期待 FDA 能夠批准我們的預充式註射器，如果獲得批准，將為視網膜專家提供更多便利，並進一步提升 EYLEA HD 的知名度。

While EYLEA HD grew, EYLEA 2 milligrams fourth quarter US net sales declined 15% sequentially to $577 million. Together, EYLEA HD and EYLEA continued to lead the innovative branded anti-VEGF category.

儘管EYLEA HD銷售成長，但EYLEA 2毫克第四季美國淨銷售額較上季下降15%至5.77億美元。EYLEA HD 與 EYLEA 攜手持續引領創新品牌抗 VEGF 品類。

Looking ahead, we remind you of two separate factors that will impact early 2026. The first quarter is typically impacted by patient reauthorizations. And as we disclosed earlier this month, wholesaler inventory levels were elevated by approximately $30 million at the end of the fourth quarter for EYLEA HD as well as EYLEA. We expect first quarter net sales will be negatively impacted as the inventory is absorbed.

展望未來，我們提醒您有兩個因素將對 2026 年初產生影響。第一季通常會受到患者重新授權的影響。正如我們本月稍早披露的那樣，截至第四季度末，EYLEA HD 和 EYLEA 的批發商庫存水準增加了約 3000 萬美元。我們預計，由於庫存需要消化，第一季淨銷售額將受到負面影響。

For EYLEA HD, we anticipate high single-digit sequential demand growth in the first quarter, while EYLEA demand is expected to decline at a double-digit rate based on competition and importantly, ongoing conversion to EYLEA HD.

對於 EYLEA HD，我們預計第一季需求將實現高個位數環比增長，而由於競爭以及更重要的，EYLEA 的需求預計將以兩位數的速度下降，這是由於持續向 EYLEA HD 的轉換所致。

Turning now to Dupixent, which delivered $4.9 billion in the fourth quarter global net sales, representing 32% year-over-year growth on a constant currency basis. US net sales grew 36% year-over-year to $3.7 billion based on broad demand growth and strong performance across several ongoing launches. Dupixent is now approved in eight Type 2 inflammatory diseases and is the number one prescribed biologic among dermatologists, pulmonologists, allergists, ear, nose, and throat specialists based on the combination of its differentiated efficacy, safety, and treatment experience.

現在來看 Dupixent，該公司第四季全球淨銷售額為 49 億美元，以固定匯率計算年增 32%。受市場需求全面成長和多款新品上市表現強勁的推動，美國淨銷售額年增 36% 至 37 億美元。Dupixent 目前已獲準用於治療八種 2 型發炎性疾病，並且憑藉其差異化的療效、安全性和治療經驗，成為皮膚科醫生、肺科醫生、過敏科醫生、耳鼻喉科醫生處方量最高的生物製劑。

Across Dupixent's established indications, including atopic dermatitis, asthma, nasal polyps, and eosinophilic esophagitis, Dupixent continues to deliver robust demand growth supported by strong physician preference in each of these indications. We've also seen remarkable uptake in our more recent launches, including COPD, chronic spontaneous urticaria, as well as prurigo nodularis, and with physicians regularly sharing their experiences on how Dupixent has changed the lives of their patients, many of whom previously had no approved treatment options. With many indications still significantly underpenetrated, Dupixent continues to be well positioned to deliver near, medium and long-term growth.

在 Dupixent 已確立的適應症範圍內，包括異位性皮膚炎、氣喘、鼻息肉和嗜酸性食道炎，Dupixent 在這些適應症中持續保持強勁的需求增長，這得益於醫生對這些適應症的強烈偏好。我們也看到，我們最近推出的產品，包括 COPD、慢性自發性蕁麻疹以及結節性癢疹，都獲得了顯著的市場認可。醫生也經常分享他們使用 Dupixent 後，患者的生活發生了怎樣的變化，其中許多患者以前都沒有獲批的治療方案。由於許多適應症的市場滲透率仍然很低，Dupixent 仍處於有利地位，預計將實現近期、中期和長期成長。

Turning to oncology and hematology. Libtayo reported $425 million in global net sales in the fourth quarter, up 13% year-over-year on a constant currency basis. In the US, net sales grew 14% year-over-year to $285 million based on strong demand growth across all approved indications. Libtayo is the leading immunotherapy for advanced non-melanoma skin cancers our recent launch in adjuvant CSCC is off to a great start, including the recent addition of Libtayo in the NCCN guidelines as the only Category 1 preferred immunotherapy in this setting.

轉向腫瘤學和血液學。Libtayo 公佈第四季全球淨銷售額為 4.25 億美元，以固定匯率計算年增 13%。在美國，由於所有核准適應症的需求強勁成長，淨銷售額年增 14%，達到 2.85 億美元。Libtayo 是治療晚期非黑色素瘤皮膚癌的領先免疫療法，我們最近在輔助性 CSCC 治療中推出的產品取得了良好的開端，包括最近將 Libtayo 添加到 NCCN 指南中，作為該領域唯一的 1 類首選免疫療法。

In advanced non-small cell lung cancer, Libtayo is now the second most commonly prescribed treatment for patients receiving their first immunotherapy. Physicians increasingly recognize Libtayo as a preferred treatment option based on clinical experience, versatility as a monotherapy in combination with chemotherapy, supported by an increasing body of robust clinical data including recently reported five-year survival results.

對於晚期非小細胞肺癌，利必妥（Libtayo）現在是接受首次免疫療法的患者中第二常用的治療藥物。基於臨床經驗、作為單藥療法與化療聯合療法的多功能性，以及越來越多的可靠臨床數據（包括最近報道的五年生存率結果），醫生們越來越認可 Libtayo 是一種首選治療方案。

Briefly turning to Lynozyfic, our new treatment for relapsed refractory multiple myeloma. We are encouraged by the launch progress to date. With physicians appreciating Lynozyfic's differentiated clinical profile, less burdensome hospitalization requirements, and convenience dosing regimen, we expect adoption to continue to steadily build over time in this late-line setting with the larger commercial opportunities in earlier lines of therapy.

簡單介紹 Lynozyfic，這是我們治療復發難治性多發性骨髓瘤的新療法。我們對目前的發布進展感到鼓舞。由於醫生們對 Lynozyfic 的差異化臨床特性、較少的住院要求和便捷的給藥方案表示讚賞，我們預計隨著時間的推移，該藥物在後線治療中的應用將繼續穩步增長，而早期治療中的商業機會更大。

In summary, in the fourth quarter, we delivered strong growth across EYLEA HD, Dupixent, and Libtayo, and we continue to progress several launches, including Lynozyfic. In 2026, our commercial portfolio is well positioned to capitalize on many near-term growth opportunities, enabling us to deliver more treatments to patients.

總而言之，在第四季度，我們在 EYLEA HD、Dupixent 和 Libtayo 方面實現了強勁增長，我們繼續推進多項產品的上市，包括 Lynozyfic。到 2026 年，我們的商業產品組合已做好充分準備，能夠抓住許多近期增長機遇，從而為患者提供更多治療方案。

With that, I will turn the call to Chris.

接下來，我將把電話轉給克里斯。

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

謝謝你，瑪莉安。除非另有說明，我今天對 Regeneron 的財務業績和展望的評論將以非 GAAP 準則為基礎。

Fourth quarter 2025 total revenues of $3.9 billion grew 3% compared to the prior year, reflecting higher collaboration revenue driven by strong global Dupixent sales growth, continued growth in net sales of EYLEA HD and Libtayo as well as higher other revenue, partially offset by lower net sales of EYLEA 2 milligrams. Fourth quarter diluted net income per share was $11.44 on net income of $1.2 billion.

2025 年第四季總收入為 39 億美元，比上年增長 3%，這主要得益於 Dupixent 全球銷售強勁增長帶來的合作收入增加、EYLEA HD 和 Libtayo 淨銷售額的持續增長以及其他收入的增加，但部分被 EYLEA 2 毫克淨銷售額的下降所抵消。第四季稀釋後每股淨收益為 11.44 美元，淨收益為 12 億美元。

Beginning with the Sanofi collaboration, fourth quarter total Sanofi collaboration revenues were approximately $1.6 billion, of which $1.5 billion related to our share of collaboration profits. Regeneron's share of profits grew 42% versus the prior year primarily driven by Dupixent and improving collaboration margins.

從與賽諾菲的合作開始，第四季度賽諾菲合作總收入約為 16 億美元，其中 15 億美元與我們應得的合作利潤有關。再生元公司利潤份額較上年增長 42%，主要得益於 Dupixent 的上市和合作利潤率的提高。

The Sanofi development balance was just below $600 million at the end of the year reflecting a reduction of approximately $300 million since the end of the third quarter and over $1 billion in full year 2025. Dupixent's continued strength enabled a rapid reimbursement of the development balance in 2025, which we now expect to be fully reimbursed by mid-2026. Once fully reimbursed, Sanofi collaboration revenues will reflect our full share of global profits for Dupixent and Kevzara.

截至年底，賽諾菲的研發資金餘額略低於 6 億美元，較第三季末減少了約 3 億美元，預計到 2025 年全年將超過 10 億美元。Dupixent 的持續強勁表現使得 2025 年的研發餘額得以迅速償還，我們現在預計到 2026 年年中將全部償還。一旦全部款項到位，賽諾菲的合作收入將反映出我們在 Dupixent 和 Kevzara 全球利潤中所佔的全部份額。

Moving to Bayer. Fourth quarter net sales of EYLEA and EYLEA 8 milligrams outside the US were $817 million, inclusive of $312 million of EYLEA 8-milligram sales. Total Bayer collaboration revenue was $319 million, of which $270 million related to our share of net profits outside the United States.

加入拜耳公司。第四季度，EYLEA 和 EYLEA 8 毫克在美國以外的淨銷售額為 8.17 億美元，其中包括 EYLEA 8 毫克銷售額 3.12 億美元。拜耳合作總收入為 3.19 億美元，其中 2.7 億美元與我們在美國以外的淨利潤份額有關。

Other revenue, which includes profit share and royalties associated with license agreements as well as amounts earned for contract manufacturing grew 33% in the fourth quarter to $239 million. This included $179 million related to royalty income from Alaris plus our share of profits from ARCALYST.

其他收入（包括與許可協議相關的利潤分成和特許權使用費以及合約製造收入）在第四季度增長了 33%，達到 2.39 億美元。這其中包括來自 Alaris 的 1.79 億美元特許權使用費收入，以及我們從 ARCALYST 獲得的利潤份額。

Alaris net sales exceeded $1.5 billion in 2025 and achieving the top royalty tier of 15% for the first time. Per our agreement with Novartis, escalating royalty tiers, which range from 4% to 15% are applied to cumulative net sales from the start of each calendar year. This leads to the step-ups and royalty income each quarter as higher royalty tiers are applied to cumulative net sales.

Alaris 2025 年淨銷售額超過 15 億美元，並首次達到 15% 的最高版稅等級。根據我們與諾華公司的協議，自每個日曆年年初起，累計淨銷售額將以 4% 至 15% 的遞增特許權使用費等級進行計算。隨著累計淨銷售額適用更高的特許權使用費等級，每季都會出現階梯式成長和特許權使用費收入。

Now to our operating expenses. R&D expense was $1.3 billion in the fourth quarter, reflecting continued investments to support Regeneron's innovative pipeline, including multiple late-stage opportunities. Fourth quarter SG&A was $691 million, inclusive of a matching contribution to the Good Days' Retinal Vascular and Neovascular Disease Fund of approximately $60 million.

接下來是我們的營運費用。第四季研發支出為 13 億美元，反映了為支持 Regeneron 的創新產品線（包括多個後期研發機會）而進行的持續投資。第四季銷售、一般及行政費用為 6.91 億美元，其中包括向 Good Days 視網膜血管和新生血管疾病基金提供的約 6,000 萬美元的配捐。

Our effective tax rate in the fourth quarter was 17%. The increase in our tax rate from the prior year primarily reflects a lower tax benefit from stock-based compensation. Regeneron generated $4.1 billion in free cash flow in 2025 and ended the quarter with cash and marketable securities less debt of $16.2 billion.

第四季我們的實際稅率為17%。與前一年相比，我們稅率的上升主要反映了股票選擇權激勵帶來的稅收優惠減少。Regeneron 預計 2025 年將產生 41 億美元的自由現金流，並在季度末持有現金及有價證券減去債務後為 162 億美元。

We returned $3.8 billion to shareholders in 2025, primarily through $3.4 billion in share repurchases. We continue to be opportunistic buyers of our shares, with $1.5 billion remaining authorized for repurchases as of December 31.

2025年，我們向股東返還了38億美元，其中34億美元主要透過股票回購實現。我們將繼續伺機回購我們的股票，截至 12 月 31 日，我們仍有 15 億美元的授權回購額度。

We also initiated a quarterly dividend last year, providing us with additional flexibility to return capital to shareholders. In 2025, we paid nearly $400 million in cash dividends and announced this morning that our Board of Directors has authorized a quarterly dividend of $0.94 per share payable in March equivalent to $3.76 on an annual basis. We continue to view our dividend as a way to expand the pool of potential Regeneron's shareholders to include funds with a dividend mandate while share repurchases will remain the primary means of returning capital to our shareholders.

去年我們也開始實施季度分紅，這讓我們有更大的彈性向股東返還資本。2025 年，我們支付了近 4 億美元的現金股息，並於今天上午宣布，我們的董事會已批准每季派發每股 0.94 美元的股息，將於 3 月支付，相當於每年 3.76 美元。我們仍然將分紅視為擴大 Regeneron 潛在股東群體的一種方式，以納入具有分紅目標的基金，而股票回購仍將是向股東返還資本的主要手段。

I will conclude with our financial guidance for 2026. Consistent with what was provided at the JPMorgan conference a few weeks ago, we expect 2026 R&D spend to be in the range of $5.9 billion to $6.1 billion. The increase versus 2025 is driven by cost to support our expanding late-stage pipeline including new Phase 3 studies in oncology and hem/onc are Factor XI antibodies and our obesity program.

最後，我將給出我們2026年的財務預期。與摩根大通會議上幾週前提供的資訊一致，我們預計 2026 年研發支出將在 59 億美元至 61 億美元之間。與 2025 年相比，成長的驅動因素是支持我們不斷擴大的後期研發管線的成本，包括腫瘤學和血液/腫瘤學領域的新 3 期研究、因子 XI 抗體以及我們的肥胖症計畫。

In addition, as you heard from George, we plan on advancing several new molecules into the clinic across a number of different therapeutic areas, including ophthalmology and [I&I]. We expect 2026 SG&A to be in the range of $2.5 million to $2.65 billion, reflecting investments to support the ongoing launches of Libtayo and adjuvant CSCC and Lynozyfic and late-line multiple myeloma, as well as other potential launches, including cemdisiran and gMG.

此外，正如喬治所說，我們計劃在多個不同的治療領域（包括眼科和…）推進幾種新分子進入臨床試驗。[I&I]。我們預計 2026 年的銷售、一般及行政費用將在 250 萬美元至 26.5 億美元之間，這反映了對 Libtayo 和輔助性 CSCC 以及 Lynozyfic 和晚期多發性骨髓瘤的持續上市，以及其他潛在上市（包括 cemdisiran 和 gMG）的投資。

We expect our gross margin and net product sales to be in the range of 83% to 84%. This guidance reflects a change in product mix as well as cost to support expanding our bulk manufacturing capacity and fill-finish capabilities. We also expect 2026 capital expenditures to be in the range of $1.1 billion to $1.3 billion, primarily related to the ongoing expansion of the R&D facilities at our Tarrytown headquarters and investments in our manufacturing network to support our growing commercial portfolio and pipeline.

我們預計毛利率和淨產品銷售額將在 83% 至 84% 之間。此指導意見反映了產品組合的變化以及為支持擴大我們的散裝生產能力和填充包裝能力而進行的成本調整。我們也預計 2026 年的資本支出將在 11 億美元至 13 億美元之間，主要與我們在塔里敦總部的研發設施的持續擴建以及對我們製造網絡的投資有關，以支持我們不斷增長的商業組合和產品線。

Finally, we expect our 2026 effective tax rate to be in the range of 13% to 15%. It is important to note that our 2025 effective tax rate benefited from a favorable tax audit settlement, which reduced our 2025 ETR by 1.2 percentage points. A full summary of our guidance can be found in our earnings press release published earlier this morning.

最後，我們預計 2026 年的實際稅率將在 13% 至 15% 之間。值得注意的是，我們 2025 年的實際稅率得益於一項有利的稅務審計和解協議，該協議使我們 2025 年的實際稅率降低了 1.2 個百分點。有關我們業績指引的完整摘要，請參閱今天早上早些時候發布的盈利新聞稿。

In conclusion, Regeneron's strong performance in 2025 positions us well to continue investing in our differentiated pipeline to deliver significant advances for patients and deploying capital to drive long-term value for shareholders.

總之，Regeneron 在 2025 年的強勁表現使我們能夠繼續投資於我們差異化的研發管線，為患者帶來重大進展，並部署資本為股東創造長期價值。

With that, I'll pass the call back to Ryan.

這樣，我就把電話轉回給瑞恩了。

Thank you, Chris. This concludes our prepared remarks. We will now open the call for Q&A. (Event Instructions). Shannon, can we please move to the first question.

謝謝你，克里斯。我們的發言稿到此結束。現在開始問答環節。（活動說明）香農，我們能進入第一個問題了嗎？

(Operator Instructions) Alexandria Hammond, Wolfe Research.

（操作說明）亞歷山德里亞·哈蒙德，沃爾夫研究公司。

So clearly, there's a ton of interest in the upcoming as for Libtayo film. So in metastatic melanoma and adjuvant, any update on when we could receive this data beyond first half? Should we expect to get an adjuvant interim update with the metastatic?

顯然，大家對即將上映的 Libtayo 電影非常感興趣。那麼，關於轉移性黑色素瘤和輔助治療，除了上半年的數據之外，我們何時才能獲得這些數據？我們是否可以期待獲得轉移性疾病的輔助治療中期進展報告？

And I guess as a follow-up, we know there are several interims for the adjuvant. So if we don't get an update on the adjuvant with the metastatic readout, when could we expect that next interim?

我想作為後續，我們知道輔助治療有幾個過渡階段。如果轉移性結果的輔助治療方面沒有更新訊息，我們什麼時候才能等到下一次中期結果？

Thanks, Alex. We don't really have any additional clarity right now on the timing for the advanced melanoma readout. First half is the best estimate at this time.

謝謝你，亞歷克斯。目前我們對晚期黑色素瘤的檢測結果公佈時間還沒有更明確的資訊。目前來看，上半年是最佳預估。

In terms of the adjuvant timing, that's also in the first half. They may coincide. They may not. Once we have the data, we will read it out shortly thereafter.

就佐劑用藥時間而言，那也是在上半程。它們可能同時出現。他們可能不會。一旦我們獲得數據，我們將盡快將其讀出。

Chris Raymond, Raymond James.

克里斯·雷蒙德，雷蒙德·詹姆斯。

Just a question on Dupixent IP. I'm sure you're aware of Sanofi's commentary yesterday about taking potential for taking the runway out well beyond the current thinking, and I think their commentary took things out maybe to the [2040] or beyond range. I know you don't want to get too much detail here, Len, but maybe any commentary you can provide in light of those comments yesterday.

關於Dupixent IP的問題。我相信您已經了解了賽諾菲昨天發表的評論，他們表示有可能將跑道延長到遠遠超出目前設想的範圍，我認為他們的評論將時間範圍擴大到了 2040 年甚至更遠。我知道你不想透露太多細節，Len，但或許你可以根據昨天的那些評論提供一些看法。

No. No additional comments. I thought Sanofi did a good job laying out what the realm possibilities are.

不。沒有其他意見。我認為賽諾菲很好地闡述了該領域的可能性。

I think we should highlight the fact that we have also a lot of exciting follow-on opportunities in this space, particularly with our collection of what we hope will prove to be the best-in-class long-acting IL-13, IL-4, and IL 413 bispecifics as well as what we call a new souped-up Dupixent molecule that is a new version of Dupixent that was naturally selective that might have even more improved properties.

我認為我們應該強調，我們在這個領域還有很多令人興奮的後續機會，特別是我們擁有一系列我們希望能夠成為同類最佳的長效 IL-13、IL-4 和 IL 413 雙特異性抗體，以及我們稱之為新型增強型 Dupixent 分子的藥物，它是 Dupixent 的新版本，具有天然選擇性，可能具有更優異的性能。

I think it's worth just highlighting again because a lot of people don't realize how special Dupixent is. In terms of -- not only its remarkable efficacy, how I mean, it delivers -- it doesn't just help a little. It really dramatically benefits patients across these eight now approved diseases. But the thing that I think is underappreciated is its incredible safety profile.

我覺得有必要再強調一下，因為很多人沒有意識到Dupixent有多特別。就其效果而言——不僅僅是它顯著的功效，我的意思是，它確實有效——它不僅僅是有點幫助。它確實能極大地造福這八種已獲批准疾病的患者。但我認為它最被低估的一點是它極高的安全性能。

And I think that -- we've all seen now so many people are trying all sorts of other approaches to go after some of the same disease like atopic dermatitis. We're seeing data, let's say, with OX40 and OX40 ligand which I think most people now realize they're somewhat [porting] not only from the efficacy side, but perhaps even most importantly, from the safety side. What people, I think, don't appreciate and understand is when we discovered Dupixent in this whole -- understood this whole pathway, we realized that this was a specific pathway that was driving only allergic disease and it was a [vestigial] -- largely a vestigial part of the immune system that was no longer required to fight most pathogens.

而且我認為——我們現在都看到很多人正在嘗試各種其他方法來治療同一種疾病，例如異位性皮膚炎。我們看到的數據，例如 OX40 和 OX40 配體，我認為現在大多數人都意識到，它們在某種程度上不僅在療效方面，而且可能更重要的是，在安全性方面，都具有一定的借鑒意義。我認為人們沒有意識到和理解的是，當我們發現 Dupixent 並理解了整個通路時，我們意識到這是一個專門驅動過敏性疾病的特定通路，它是免疫系統中一個（退化的）部分，不再需要它來對抗大多數病原體。

That's why unlike most other immunomodulators, it doesn't suppress overall immunity. When you suppress overall immunity with things like [JAK] inhibitors or things like [Oppligand], you suppress everything and then you raise concerns and fears the possibility that the general immunosuppression will now subject the patients to more infections, which is generally actually what we see. And remarkably, with Dupixent, you don't see these sorts of things.

這就是為什麼它不像大多數其他免疫調節劑會抑制整體免疫力的原因。當你使用 JAK 抑制劑或 Oppligand 等藥物抑制整體免疫力時，你抑制了所有免疫力，然後你會擔心，整體免疫抑制可能會使患者更容易感染，而這通常也是我們所看到的。值得注意的是，使用 Dupixent 時，你不會看到這類情況。

So you don't see general line increases in infections. We don't have black box warnings on sections because we're not generally suppressing the immune system. We're only suppressing the part of the immune system, which is largely [vestigial] and is largely activated in our modern world for reasons we have theories about, but won't get into now, that drive allergic inflammation. So it's a very special approach and you don't have to worry about, for example, getting Kaposi sarcoma or things like that with treatment with.

所以你不會看到感染人數普遍上升。我們沒有在藥品說明書上添加黑框警告，因為我們通常不會抑制免疫系統。我們只是抑制了免疫系統的一部分，這部分免疫系統在很大程度上是（退化的），並且在我們現代社會中很大程度上被激活，其原因我們有一些理論，但現在就不深入探討了，它驅動著過敏性炎症。所以這是一種非常特殊的治療方法，例如，您不必擔心在接受治療後會患上卡波西氏肉瘤之類的疾病。

Salveen Richter, Goldman Sachs.

薩爾文·里克特，高盛。

Just a follow-up here on the frontline metastatic melanoma data in the first half. Is there any way you could frame for us how to think about the bar on hazard ratio here? And just any commentary about the PD-L1 expression levels of these patients as we look to this first interim read?

這裡是對上半年一線轉移性黑色素瘤數據的後續補充。您能否為我們解釋一下這裡風險比率的下限是什麼？對於這些患者的PD-L1表現水平，大家有什麼看法？這是我們第一次進行中期分析的結果。

I think as we've discussed before, this study is largely powered to get an effect in terms of the primary endpoint, which is the PFS analogous to the current combination standard of care. I hope -- of course, we hope that we might actually achieve better. We have two dose groups in the study and so forth. But we're also powered that if we were to hit at that level as the current standard of care. We would also hope to demonstrate a benefit in the study is appropriately powered to pick up an overall survival benefit. That is the minimum hopeful expectations, and we might we might see better than that as well.

我認為正如我們之前討論過的，這項研究的主要目的是在主要終點（即 PFS，類似於目前的聯合標準治療）方面取得成效。我希望——當然，我們都希望我們能夠取得更好的成績。本研究設有兩組劑量組，以此類推。但我們也相信，如果我們能達到目前的照護標準，我們就能達到更大的成就。我們也希望證明，該研究具有足夠的統計效力，能夠發現整體存活獲益。這是最低的樂觀預期，我們或許也能看到更好的結果。

And regarding PD-L1 status of the enrollment, we are not -- we are screening patients, but we are not using it as an inclusion or exclusion criteria. There's no forward cap meaning the patients with high expression or low expression. So this population, we expect would represent a true first-line advanced melanoma population. And we look forward to the results.

至於入組患者的 PD-L1 狀態，我們並沒有——我們正在篩選患者，但我們並沒有將其作為納入或排除標準。沒有前向上限，這意味著沒有高表達或低表達的患者。因此，我們預計該族群將代表真正的一線晚期黑色素瘤患者群體。我們期待結果。

Tyler Van Buren, TD Cowen.

泰勒·範·布倫，TD·考恩。

I wanted to ask about broader R&D strategy. In your presentation, you have the slide where you divide your pipeline among the six therapeutic areas and [I&I] has expanded significantly as of late as well as ophthalmology, which is not terribly surprising, and I would argue is necessary given the history of the company. So would you say that these two areas in addition to oncology, will remain a bigger focus than the three others? Or are you committed to remaining relatively balanced across all six areas over the next few years?

我想詢問一下更廣泛的研發策略。在您的簡報中，您有一張幻燈片，將您的產品線劃分為六個治療領域，[免疫和免疫] 近期以及眼科領域都得到了顯著擴展，這並不令人驚訝，而且考慮到公司的歷史，我認為這是必要的。那麼，您認為除了腫瘤學之外，這兩個領域將比其他三個領域更受關注嗎？或者，您是否致力於在未來幾年內保持所有六個領域的相對平衡？

Well, Tyler, thanks for bringing that up. First of all, I do want to point out that we are somewhat disappointed with the industry in that we invent a great leading drug like EYLEA and then you get literally dozens and dozens of companies just trying to come up with a me-too and take a little bit of that business or the same thing with DUPIXENT. They're just trying to come up and try to mimic Dupixent and maybe try to make a little incremental improvement.

泰勒，謝謝你提出這個問題。首先，我想指出，我們對這個行業感到有些失望，因為我們發明了像EYLEA這樣優秀的領先藥物，然後就有幾十家公司試圖推出仿製藥，搶佔一點市場份額，DUPIXENT也是如此。他們只是想跟上潮流，模仿 Dupixent，或許還能做出一些小小的改進。

What our goal is to really do what I think this industry should be doing, which is taking advantage of the most innovative approaches to come up with new drugs for new indications. And what we do is we take an agnostic approach that is generally guided by genetics, which has proven to be so successful in our history.

我們的目標是真正做我認為這個行業應該做的事情，那就是利用最具創新性的方法來研發針對新適應症的新藥。我們採取的是一種不可知論的方法，這種方法通常以遺傳學為指導，而這在我們的歷史上已被證明是非常成功的。

This is perhaps one of the first, if not the first company that its entire future on the power of genetics, first mouse and now human genetic. So we make our choices based on the most powerful available data and technology that can guide decision-making, which is large-scale human genetics, which allows us to use AI in ways that other people can't. And that allows us to pick targets.

這或許是第一家（如果不是第一家）將整個未來都寄託在基因技術的公司，原本是小鼠基因技術，現在是人類基因技術。因此，我們根據最強大的可用數據和技術來做出選擇，這些數據和技術可以指導決策，即大規模人類遺傳學，這使我們能夠以其他人無法做到的方式使用人工智慧。這樣我們就可以挑選目標了。

So many of the targets that we've now described, for example, in ophthalmology and in immunology and inflammation, but across other areas of wealth are driven by the same kind of genetic that allows us to know whether Dupixent will work in an indication enough. That is the genetic says that if you're missing that genetic pathway, you're likely going to help your disease and if you have increases in that genetic, you're going to get more of that disease. And that has proven very powerful for us to make a decision.

我們現在描述的許多目標，例如眼科、免疫學和炎症，以及其他財富領域，都是由同一種基因驅動的，這使我們能夠知道 Dupixent 是否對某種適應症有效。基因學說表明，如果你缺少某種基因通路，你很可能會加重病情；而如果這種基因通路增強，你就會患上更嚴重的疾病。事實證明，這對我們做出決定非常有幫助。

That's how we find indication. We are therapeutic agnostic, but obviously, we have capabilities broadly across all these areas, but we are very excited about these new programs because like our previous success, they are driven by human genetics, telling us that these targets if we can make, and we believe we have the most powerful technologies to address these targets, whether it be antibodies bispecifics, genetic method.

這就是我們尋找跡象的方法。我們對治療方法持開放態度，但顯然，我們在所有這些領域都具備廣泛的能力，但我們對這些新項目感到非常興奮，因為與我們之前的成功一樣，它們是由人類遺傳學驅動的，告訴我們，如果我們能夠製造這些靶點，我們相信我們擁有最強大的技術來解決這些靶點，無論是抗體、雙特異性抗體還是基因方法。

If we properly can target these genetically validated, we can create new opportunities, new drugs for new indications, not just also protecting our existing franchisees by making sure that we always have the best anti-VEGF approach and portfolio. We have the best [antiology] portfolio and so forth. When we want to break new ground, we're doing it across all these therapeutic areas, we're very excited about.

如果我們能夠正確地針對這些經過基因驗證的靶點，我們不僅可以創造新的機會，開發針對新適應症的新藥，還可以透過確保我們始終擁有最佳的抗 VEGF 方法和產品組合來保護我們現有的特許經營權。我們擁有最好的[抗藥性]產品組合等等。當我們想要開拓新領域時，我們會在所有這些治療領域中嘗試，我們對此感到非常興奮。

Dave Risinger, Leerink Partners.

Dave Risinger，Leerink Partners。

So my question is for George. George, could you talk a little bit more about the souped-up version of Dupixent that's in development, including the event path ahead?

所以我的問題是問喬治的。喬治，你能否再詳細談談正在開發的 Dupixent 升級版，包括未來的活動路線？

Yes. Obviously, Dupixent is a very unusual antibody. I don't know if everybody remembers the history of it, but some of the biggest companies in the world try to make a molecule like Dupixent and sales in clinical trials, for example, Amgen using an inferior humanized mouse approach try to make a Dupixent that is starting the same receptor as we did and their body completely failed in all their clinical trials.

是的。顯然，Dupixent 是一種非常不尋常的抗體。我不知道大家是否還記得這段歷史，但世界上一些最大的公司都試圖製造像 Dupixent 這樣的分子，並在臨床試驗中進行銷售。例如，安進公司使用一種較差的人源化小鼠方法，試圖製造一種與我們相同的受體結合的 Dupixent，但他們在所有臨床試驗中都徹底失敗了。

So Dupixent was apparently a special molecule. What we continue to do is use our best technologies, our best antibody generating technology, starting with our best-in-class human immune system in a mouse generating millions and millions of versions over the last many, many years and testing them in comparing.

所以，Dupixent顯然是一種特殊的分子。我們一直在做的，就是運用我們最好的技術，我們最好的抗體生成技術，從我們一流的人類免疫系統開始，在小鼠體內生成了數百萬個版本，並在過去的許多年裡對它們進行測試和比較。

And we think that we have one that might actually be in some ways, even better than Dupixent. It looks like it may be longer acting and they have some other advantages as well. So we're going to be moving it forward in the clinic as we announced and we'll be testing it, and we'll see whether indeed. We have been able to come up with an even better Dupi or [supi-Dupi], as we call it.

我們認為我們開發的這種藥物在某些方面甚至可能比 Dupixent 更好。它似乎藥效更持久，而且還有其他一些優點。因此，我們將按照先前宣布的方式，在臨床試驗中推進這項研究，並進行測試，看看是否真的有效。我們已經開發了一種更好的 Dupi，或者我們稱之為 [supi-Dupi]。

And just to remind everybody that while not formally in the alliance with Sanofi, it is covered by the alliance, meaning that if it goes into full development that we'll be doing this with Sanofi.

再次提醒大家，雖然我們沒有正式加入賽諾菲聯盟，但該項目已納入聯盟範圍，這意味著如果該項目進入全面開發階段，我們將與賽諾菲合作進行。

Tazeen Ahmad, Bank of America.

塔津·艾哈邁德，美國銀行。

I wanted to spend a minute on geographic atrophy. You guys have a cohort, I believe, reading out in the second half of this year on your GA program. I think there was a lot of promise a few years back just given the number of patients with GA, but the two approved drugs have proven not to be able to get a ton of market share. So what do you think is differentiated in your program? Do you think that you'll need to show a visual acuity benefit? Or is it going to be in your mind, it's just as good to show slowing of vision loss, given that you expect to have a better safety profile than both those drugs.

我想花一分鐘時間談談地理萎縮。我相信你們今年下半年會有一批學生參加研究所畢業論文宣讀會。幾年前，考慮到 GA 患者的數量，我認為這種療法很有前景，但事實證明，兩種核准的藥物並沒有獲得很大的市場份額。那麼，你認為你們的課程有哪些獨特之處呢？你認為你需要證明你的視力有優勢嗎？或者，這只是你的個人看法，考慮到它比那兩種藥物都具有更好的安全性，那麼減緩視力喪失的效果也同樣很好。

Well, let me just remind you that the first drug in the [wet AMD] space was [Macugen], which was an [aptamer]. And if you compare the benefits that it provided compared to something like EYLEA, yes, it had a benefit but it was just barely slowing down wet AMD disease as opposed to what we were able to do with EYLEA where we could actually reverse and improve vision even and maintain or maintain the restored vision for years thereafter.

嗯，我得提醒你一下，第一個針對濕性AMD的藥物是Macugen，它是一種[適體]。如果將它提供的益處與 EYLEA 之類的藥物進行比較，是的，它確實有益處，但它只是勉強減緩了濕性 AMD 的病情發展，而 EYLEA 則可以真正逆轉甚至改善視力，並在之後的幾年內保持或維持恢復後的視力。

So obviously, the approaches that we have at our disposal, things like our antibodies and our sRNAs have historically proven to be much more powerful at blocking pathways, then technologies approaches such as active [pegylated] does and [pegylated] peptides and so forth. So one possibility and opportunity, of course, is that by providing more profound blockade, one might actually see better benefit.

顯然，我們現有的方法，例如我們的抗體和 sRNA，在阻斷路徑方面，已經證明比活性[聚乙二醇化]D 和[聚乙二醇化]勝肽等技術方法要有效得多。當然，一種可能性和機會是，透過實施更深層的封鎖，或許能夠獲得更大的利益。

Another, of course, important aspect of our program is we are trying both systemic blockade as well as local blocking. So one of the problems with the existing therapies and why they're not so widely used, they're largely [preventages], but they come with very dangerous side effects in that they can cause essentially problems that might resolve intermediate blindness like retinal vasculitis with occlusive vasculitis disease.

當然，我們方案的另一個重要面向是，我們正在嘗試系統性阻斷和局部阻斷。因此，現有療法存在的問題之一，也是它們沒有被廣泛應用的原因，是它們大多是預防性的，但它們會帶來非常危險的副作用，因為它們可能會導致一些問題，例如視網膜血管炎伴隨閉塞性血管炎等中度失明。

So imagine you're taking something to prevent the line that can actually cause blindness. So the systemic approach, now of course, they may have its own problems, there's always risk. So they come with its own problems in terms of systemic infection, but it should be free from causing these local potential blinding risks in the eye. So you may end up either with better efficacy or the same efficacy but with a better safety profile in terms of avoiding these blinding risks.

想像一下，你服用某種藥物是為了預防這種線狀物，但這種藥物其實會導致失明。所以，系統性的方法當然也有它本身的問題，總是存在著風險的。因此，它們在全身感染方面有自身的問題，但應該不會造成眼睛局部潛在的致盲風險。因此，最終可能會獲得更好的療效，或療效相同但安全性更高，從而避免這些致盲風險。

And also, in the case of right now, the current treatments, most patients actually have bilateral disease. So you have to inject both eyes. And many of them also suffer now. And in fact, these drugs can actually, in some cases, cause wet AMD, progression [wet AMD], they need the injections in both eyes, and they also need injections with anti-VEGF.

而且，就目前的情況而言，大多數患者實際上患有雙側疾病。所以你需要雙眼都注射。現在他們中的許多人也深受其害。事實上，在某些情況下，這些藥物實際上會導致濕性老年性黃斑部病變（濕性老年黃斑部病變）的進展，患者需要在雙眼注射藥物，並且還需要注射抗 VEGF 藥物。

So obviously, a systemic approach will avoid all these complications, you would have to give two sets of injections to both sets of eyes and so forth. So we're very excited because there's many, many opportunities here.

顯然，系統性的方法可以避免所有這些併發症，否則就需要給兩隻眼睛各注射一次，等等。所以我們非常興奮，因為這裡有很多很多機會。

And I also remind you that we are testing both the monotherapy, in terms of cemdisiran alone, which works so spectacularly in myasthenia grabs as well as the combination of some distrain with the antibody, which worked so beautifully and was required to optimally work in PNH.

我還要提醒各位，我們正在測試兩種療法：一種是單獨使用西地西蘭的單藥療法，這種療法在治療重症肌無力方面效果顯著；另一種是將西地西蘭與抗體聯合使用，這種療法效果非常好，也是治療陣發性睡眠性血紅蛋白尿症 (PNH) 的最佳療法。

We don't know because we collectively society, the medical system does not understand why in one case, you need complete blockade. In the other case, you need this sort of [segesterone] type of effect. We're exploring both. So there's many, many, many ways to provide improved benefit for these patients who really need an improved way of treating their disease.

我們不知道，因為我們整個社會、醫療系統都不明白為什麼在某些情況下需要完全封鎖。另一種情況下，你需要這種[黃體酮]類型的效果。我們正在對兩者進行探索。因此，有很多很多方法可以為這些真正需要改進疾病治療方法的患者帶來更好的益處。

It could be something that really addresses the tremendous bird that's inflicted by palatal disease, layered with anti-VEGF requirements and so forth. It could be better efficacy, it could be better safety. And it could also be for example, a systemic approach that does not completely inhibit the complement system. So many, many, many ways to imagine delivering a better outlook for patients who really need it here, especially if more of them will choose to undertake this preventative approach.

這可能是一種真正能解決腭部疾病給鳥類帶來的巨大痛苦的方法，它結合了抗 VEGF 需求等等。它可能療效更好，也可能安全性更高。例如，它也可能是一種系統性方法，不會完全抑制補體系統。有很多很多很多方法可以為真正需要的患者帶來更好的前景，特別是如果更多的患者選擇採取這種預防方法的話。

Just to add one point, which George fully emphasizes VEGF is made locally. And so you give a local drug to a local problem. The C5 is made systemically primarily in the liver. So it may require systemic blockade as opposed to individual. But we have all the tools to dissect what the best approach is.

補充一點，喬治非常強調，VEGF 是局部產生的。所以，你用當地的藥物來解決當地的問題。C5主要在肝臟中系統性合成。因此，可能需要係統性阻斷，而不是針對個體。但我們擁有所有必要的工具來分析哪一種方法才是最佳方案。

And final note on this to Tazeen. The primary endpoint of our initial pivotal study is the growth rate in GA lesion area, but I would note that we do have a prospective secondary endpoint that will measure 15-letter loss of visual acuity. So we will have an endpoint that looks at visual acuity at year one and year two of this study, unlike incumbent therapies, we looked at this on a post-op basis.

最後再跟塔津說幾句。我們最初的關鍵性研究的主要終點是 GA 病灶面積的成長率，但我需要指出的是，我們還有一個前瞻性的次要終點，即測量視力下降 15 個字母的情況。因此，我們將以本研究第一年和第二年的視力為終點，與現有療法不同，我們是在術後進行觀察的。

Geoff Meacham, Citi.

傑夫‧米查姆，花旗銀行。

Thanks, for the question. I just want to talk about EYLEA HD for a sec. Maybe just talk about the trends for growth for this year. I wanted to get maybe your perspective as you kind of exit '25 and going to '26, sources of growth with regard to new patients, switches versus competition? And then on the prefilled syringe related, do you characterize that as kind of a tipping point? Are there ophthalmologists? Are there practices that are sort of waiting for that? I want to get a sense for how much of a gating factor that is to ultimate demand.

謝謝你的提問。我只想簡單談談EYLEA HD。或許可以談談今年的成長趨勢。我想了解您在即將告別 2025 年、邁入 2026 年之際，對新患者、病患流失與競爭等方面的成長來源有何看法？那麼關於預充式註射器，您是否將其視為一個轉捩點？這裡有眼科醫生嗎？是否存在一些正在等待這種情況發生的機構或個人？我想了解這會對最終需求造成多大的限制。

And I'm going to start with the last portion on EYLEA HD and the prefilled syringe potential approval that we talked about today. And as you know from the numbers that we shared, we're making good progress with EYLEA HD in the marketplace, the recent label enhancements with Q4 weekly dosing in RVO have been very well received. And of course, prefilled syringe, as I mentioned, will be a convenience factor for offices.

接下來，我將從今天我們討論的關於EYLEA HD和預填充注射器潛在批准的最後一部分開始。正如您從我們分享的數據中了解到的，EYLEA HD 在市場上取得了良好的進展，最近針對 RVO 的 Q4 每週給藥方案的標籤改進也受到了熱烈歡迎。當然，正如我所提到的，預充式註射器對於辦公室來說將是一個便利因素。

So some that find that to be incredibly important. Obviously, we'll have a new opportunity to use EYLEA HD, but obviously, we have a lot of users today. It will only get better when we get and potentially have the prefilled syringe approval.

所以有些人認為這一點極為重要。顯然，我們將有新的機會使用 EYLEA HD，但顯然，我們目前有很多用戶。只有當我們獲得預充式註射器的批准後，情況才會變得更好。

Akash Tewari, Jefferies.

阿卡什‧特瓦里，傑富瑞集團。

On your PCSK9 GIP/GLP combo, can you talk about the co-formulation here? How are you able to deliver both drugs in a single auto-injector versus something that came to an on-body infusion? And what are the chances you partner this asset out to share the development cost? Can you characterize any of those discussions so far?

關於您的 PCSK9 GIP/GLP 組合，可以談談這裡的組合製劑嗎？你們是如何做到用一個自動注射器同時輸送兩種藥物，而不是像以前那樣透過體表輸液的方式給藥的？你將這個計畫與合作夥伴共同分擔開發成本的可能性有多大？您能否概括一下目前為止的討論內容？

We don't comment on the status of discussions. We're always open minded to deal with and enhance our shareholder value.

我們不評論討論的進展。我們始終以開放的心態來處理並提升股東價值。

But as you touched on it, that's the magic, and that's the secret of our capabilities best-in-class formulations group that delivered unprecedented formulation capability with EYLEA and EYLEA HD. It's the same people doing the same things that have figured out how to magically be able to get into an auto injector of very similar injected is just for GLP, similar sort of volume, both the antibody and a peptide.

但正如您所提到的，這就是魔力所在，也是我們一流的配方團隊擁有卓越能力的秘訣，正是這種能力，使得 EYLEA 和 EYLEA HD 擁有了前所未有的配方能力。是同一批人做著同樣的事情，他們已經神奇地掌握瞭如何將非常相似的注射物（例如抗體和肽）注入自動注射器的方法，這只是為了符合 GLP 標準，注射量也大致相同。

And so we're very excited because Len's the one who, he put it this way. Imagine inventing a GLP, that in addition to doing what -- the leading GLP do is also just lowers cholesterol, bad cholesterol, by 50% to 60%. We wouldn't everybody want to take that because we understand that so many people who suffer from obesity also suffer from cardiovascular risk. And while losing weight helps your cardiovascular is, it also was dramatically driven by the bad cholesterol, which weight loss doesn't appreciably impact.

所以我們非常興奮，因為 Len 是這麼說的。想像一下，發明了一種 GLP（良好實驗室規範），它除了具備目前領先的 GLP 所具備的功能外，還能將膽固醇（壞膽固醇）降低 50% 到 60%。我們不希望每個人都接受這種治療，因為我們了解到許多肥胖患者也面臨心血管疾病的風險。雖然減肥對心血管健康有益，但它也很大程度上是由壞膽固醇引起的，而減肥對壞膽固醇的影響並不明顯。

So it's a very, very exciting opportunity. We're very excited that our scientists we're able to figure out how to make this magic happen, and we think it's going to offer patients a really differentiated way of not only having their desirable weight loss, but also dramatically improving their [hypolipidemia] associated cardiovascular risk as well. So we're very, very excited to be able to offer this opportunity and move forward with our clinical program to see if it's a reality.

所以這是一個非常非常令人興奮的機會。我們非常興奮，我們的科學家能夠找到實現這一奇蹟的方法，我們認為這將為患者提供一種真正與眾不同的方式，不僅可以實現他們理想的減肥目標，還可以顯著改善他們與低血脂相關的心血管風險。因此，我們非常非常興奮能夠提供這個機會，並推進我們的臨床項目，看看它是否能夠實現。

Okay. We have time for two more questions, Shannon.

好的。香農，我們還有時間再問兩個問題。

Terence Flynn, Morgan Stanley.

Terence Flynn，摩根士丹利。

Bayer is going to be presenting some Phase III data for their oral Factor X inhibitor, asundexian, next week. Just wondering anything you'll be focused on in that data set as it pertains to your Factor XI antibody program in terms of development, et cetera.

拜耳將於下周公布其口服 X 因子抑制劑 asundexian 的一些 III 期臨床試驗數據。我想知道，就您的因子XI抗體專案而言，您會專注於該資料集中的哪些內容，例如開發等方面。

Yes. I mean it is very hard to compare these small molecules with antibodies. As we know, historically, and if the case here, small molecules suffer from both lack of specificity that we know they inhibit multiple [proteases] including the target of interest here. And they also have off-target effect as well.

是的。我的意思是，很難將這些小分子與抗體進行比較。眾所周知，從歷史上看，如果這裡的情況也是如此，小分子藥物缺乏特異性，我們知道它們會抑制多種蛋白酶，包括這裡感興趣的目標。它們也會產生非標靶效應。

And so the hope here is by having an antibody, which we think is very, very different than a small molecule, the specificity as well as the efficacy may allow you have a very different profile where you will actually have better anticoagulation, but also, hopefully, better safety, less bleeding, which we think what it's all about. And so there will be some read-through, there will be some usefulness to following that.

因此，我們希望透過抗體（我們認為它與小分子藥物非常非常不同），其特異性和療效可能會帶來截然不同的效果，從而實現更好的抗凝血效果，同時也有望提高安全性，減少出血，我們認為這才是關鍵所在。因此，閱讀這些內容會有一些價值，遵循這些內容也會有一些幫助。

On the other hand, we believe our antibody has a very substantial differentiated and potentially advantageous profile. And so the key thing is if our antibodies really can deliver what we believe they can with dramatic decreases in the overall bleeding risk, then they should allow somebody to essentially get an occasional shop once after a procedure, let's say, or once a month attention, things like that, that won't require these patients to be either having worried about making sure they stay on their meds or borrowing and so forth.

另一方面，我們認為我們的抗體具有非常顯著的差異化和潛在的優勢特性。因此，關鍵在於，如果我們的抗體真的能夠像我們認為的那樣，大幅降低整體出血風險，那麼它們應該能夠讓患者在手術後偶爾接受一次治療，或者每月接受一次治療等等，這樣患者就不必擔心是否堅持服藥或借藥等等。

So very different opportunity. Of course, there's some read through, but we think our antibiotic is going to be very different.

這是截然不同的機會。當然，會有一些交叉反應，但我們認為我們的抗生素將會非常不同。

Shannon, let's go to the last question, please.

香農，我們來問最後一個問題。

Evan Seigerman, BMO Capital Markets.

Evan Seigerman，BMO資本市場。

I'd love you to talk a little bit about the confidence that gives you to move your GLP-1 GIP to Phase III clinical trials globally, just given how rapidly this market is evolving. Put it another way, what's differentiated about this asset from currently available standard of care and other advanced assets in development?

鑑於這個市場發展如此迅速，我很想請您談談是什麼讓您有信心將您的 GLP-1 GIP 推進到全球 III 期臨床試驗。換句話說，這種資產與目前可用的標準療法和其他正在研發的先進資產有何不同？

So I think if you go back and listen carefully to what George is saying that the biggest advance here from our perspective is the ability to combine this with our [PCSK9] [antibody], there are only two approved PCSK9 antibodies and the ability to combine this antibody with these peptides in the same syringe at the same dosing interval, I think that's highly differentiated for the 15% -- the 50% or more people who are obese and have high cholesterol.

所以我覺得，如果你仔細聽喬治的話，你會發現從我們的角度來看，最大的進步在於能夠將這種藥物與我們的[PCSK9][抗體]結合使用。目前只有兩種核准的PCSK9抗體，而能夠將這種抗體與這些勝肽類藥物結合在同一注射器中，並在同一給藥間隔內使用，我認為這對於15%到50%甚至更多的肥胖且高膽固醇患者來說，具有很大的差異化優勢。

We know several hundred thousand people already take both a GLP and a PCSK9 inhibitor. And that's without the convenience of having to put that together in a single shot and without really focusing any marketing on the obese group. So I think, Evan, that's what the core of the differentiation could be.

我們知道已有數十萬人同時服用 GLP 和 PCSK9 抑制劑。而且這還不包括一次完成所有工作的便利性，也沒有真正將行銷重點放在肥胖群體上。所以我覺得，艾文，這可能就是差異化的核心。

Obviously, we're considering putting it together with other assets in our pipeline, other combinations we can't imagine directly competing, but I do think we should have favored that's competitive to the best-in-class. But the commercial strategy is not directly competed with that combination. George, do you want to add something?

顯然，我們正在考慮將其與我們研發管線中的其他資產結合起來，以及其他我們無法想像會直接競爭的組合，但我確實認為我們應該優先選擇能夠與同類最佳產品競爭的產品。但這種商業策略並不與該組合直接競爭。喬治，你還有什麼要補充的嗎？

Yes. So remember, one of the reasons we have confidence is there has already been extensively studied in China. And it's designed to be and the clinical data suggests it is very [prozepetide-like] in its efficacy and safety profile when compared to the same population. And it is already in advanced Phase III trials in China.

是的。所以請記住，我們充滿信心的原因之一是，中國已經對此進行了廣泛的研究。它的設計目的就是如此，臨床數據表明，與同一人群相比，它的療效和安全性與普羅澤肽非常相似。目前該藥物已在中國進入後期三期臨床試驗階段。

That's why we think we have very much a tozepatide line or a best-in-class type agent. But as Len said, we don't necessarily want to just compete just for the weight loss. A lot of people are just so focused on the weight loss load and they're trying to say, let me get a little bit more weight loss. A little less nauseousness, a little less vomiting.

這就是為什麼我們認為我們擁有非常優秀的托澤帕肽系列藥物，或者說是同類最佳的藥物。但正如 Len 所說，我們不一定想只為了減肥而參賽。很多人都太專注於減肥這件事了，他們總是想著，讓我再減掉一點體重。噁心和嘔吐的症狀減輕。

They're all competing around the weight loss. They're all fighting in that space. We want to take this to a whole other place where we're adding of completely new benefit, a completely different benefit to the weight loss. So let everybody else fight for an extra 1% or 2% of weight loss, we're going to give you 50% to 60% [LDL] lowering with the associated expected cardiovascular benefit.

他們都在競相減肥。他們都在那個區域戰鬥。我們希望將減重提升到一個全新的高度，增加一種全新的、與減重完全不同的益處。所以，讓其他人去爭取額外 1% 或 2% 的減重吧，我們將為您帶來 50% 到 60% 的 [LDL] 降低，以及相關的預期心血管益處。

That's highly differentiated. So we didn't get this to compete just by itself in the obesity space, though we think we have an agent here that is very similar to the best-in-class type of reagent. It's all about the combinations.

這差異化程度很高。因此，我們研發這款產品並不是為了讓它單獨在肥胖症領域參與競爭，儘管我們認為我們這裡有一種與同類最佳試劑非常相似的藥物。關鍵在於組合搭配。

And the first combination that we're rolling out we think is this very, very exciting one. And frankly, honestly, every obese patients should take okay, regardless of their lipid stats because lower lipids is better. And that would be better. It would, frankly, be better for the entire population.

而我們即將推出的第一個組合，我們認為非常非常令人興奮。坦白說，所有肥胖患者都應該服用，無論他們的血脂指標如何，因為血脂越低越好。那樣會更好。坦白說，這對全體民眾都有好處。

Why do we know? Because cardiovascular disease driven by [hypolipidemia] still the number one killer in America and people are not taking it. So it may be almost a Trojan horse. Imagine, they just -- they want to lose their weight and they're not even going to realize that they're going to be helping their hearts, they can decrease the overall rate of cardiovascular disease and death in this country. A Trojan horse to really make an impact for society.

我們為什麼知道？因為低血脂引起的心血管疾病仍然是美國的第一大殺手，而人們卻沒有接受治療。所以它很可能就是一匹特洛伊木馬。想像一下，他們只是想減肥，卻根本沒意識到這樣做對心臟有益，還能降低這個國家心血管疾病和死亡的整體發生率。一個真正能對社會產生影響的特洛伊木馬。

This is what we're trying to do. Everybody, frankly, in America should be on a [PCSK9]. This is a way to actually do it and do it in a way that people will actually want to take. And we think we have a variety of other ways not to compete on the weight loss side, but to give another important benefit on top of the weight loss.

這就是我們正在努力的方向。坦白說，美國每個人都應該…[PCSK9]。這是切實可行的方法，也是人們真正願意接受的方法。我們認為我們還有其他多種方法，不僅可以在減肥方面與其他品牌競爭，還能在減肥的基礎上提供其他重要的益處。

Thank you, George, and thanks to everyone who dialed in today for your interest in Regeneron. We apologize for those remaining in the Q&A queue. We do not have a chance to hear from today. As always, the IR team is available to answer any remaining questions that you may have. Once again, have a great day and a nice weekend.

謝謝喬治，也謝謝今天所有撥入電話對 Regeneron 有興趣的朋友。對於仍在問答隊列中的用戶，我們深表歉意。我們今天沒有機會聽到消息。如有任何疑問，投資人關係團隊隨時為您解答。再次祝您今天過得愉快，週末愉快！

This concludes today's conference. Thank you for your participation. You may now disconnect.

今天的會議到此結束。感謝您的參與。您現在可以斷開連線了。