雷傑納榮製藥 (REGN) 2024 Q4 法說會逐字稿

Hello, and welcome to Regeneron Pharmaceuticals' fourth quarter 2024 earnings conference call.

您好，歡迎參加再生元製藥 2024 年第四季財報電話會議。

My name is Tawanda, and I will be your operator for today's call.

我的名字是 Tawanda，我將擔任您今天的電話接線生。

(Operator Instructions) Please note that this conference is being recorded.

（操作員指示）請注意，本次會議正在錄音。

I will now turn the call over to Ryan Crow, Senior Vice President, Investor Relations.

現在我將電話轉給投資者關係資深副總裁 Ryan Crow。

Thank you, Tawanda.

謝謝你，Tawanda。

Good morning, good afternoon, and good evening to everyone listening around the world.

全世界聽眾朋友們，早安、下午好、晚上好。

Thank you for your interest in Regeneron , and welcome to our fourth quarter 2024 earnings conference call.

感謝您對 Regeneron 的關注，歡迎參加我們 2024 年第四季財報電話會議。

An archive and transcript of this call will be available on the Regeneron Investor Relations website shortly after the call ends.

本次電話會議的存檔和記錄將在會議結束後不久在 Regeneron 投資者關係網站上提供。

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.

參加今天電話會議的還有董事會聯合主席、共同創辦人、總裁兼執行長 Leonard Schleifer 博士；董事會聯席主席、共同創辦人、總裁暨首席科學官 George Yancopoulos 博士；商務執行副總裁 Marion McCourt；以及執行副總裁兼財務長克里斯費尼莫爾 (Chris Fenimore)。

After our prepared remarks, the remaining time will be available for your questions.

在我們發表準備好的發言之後，剩下的時間將用來回答你們的提問。

I would like to remind you that remarks made on today's call may include forward-looking statements about Regeneron.

我想提醒您，今天電話會議的言論可能包括 Regeneron 的前瞻性陳述。

Such statements may include, but are not limited to, those related to Regeneron and its products and business, financial forecasting guidance, development programs and related anticipated milestones, collaborations, finances, regulatory matters, payer coverage and reimbursement, intellectual property, pending litigation and other proceedings, and competition.

此類聲明可能包括但不限於與 Regeneron 及其產品和業務、財務預測指南、開發計劃和相關預期里程碑、合作、財務、監管事項、付款人承保和報銷、智慧財產權、未決訴訟和其他程序以及競爭相關的聲明。

Each forward-looking statement is tailored to the risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement.

每個前瞻性陳述都針對可能導致實際結果和事件與該陳述中的預測有重大差異的風險和不確定性而量身定制。

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, 2024, which we expect to file with the SEC tomorrow, February 5.

有關這些風險和其他重大風險的更完整描述，可在 Regeneron 向美國證券交易委員會提交的文件中找到，包括截至 2024 年 12 月 31 日的 10-K 表格，我們預計將於明天（2 月 5 日）向美國證券交易委員會提交該表格。

Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information at future events or otherwise.

無論是由於未來事件中的新資訊還是其他原因，Regeneron 都不承擔更新任何前瞻性聲明的義務。

In addition, please note that GAAP and non-GAAP financial measures will be discussed on today's call.

此外，請注意，今天的電話會議將討論 GAAP 和非 GAAP 財務指標。

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 accessed on the Regeneron Investor Relations website.

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，可在我們的季度業績新聞稿和公司介紹中找到，兩者均可在 Regeneron 投資者關係網站上查閱。

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

通話結束後，Chris 和 IR 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.

接下來，請允許我將電話轉給我們的總裁兼執行長 Leonard Schleifer 博士。

Thank you, Ryan, and thank you, everyone, for joining today's call.

謝謝瑞安，也謝謝大家參加今天的電話會議。

Regeneron capped 2024 with a strong fourth quarter, highlighted by 10% revenue growth, reflecting the strength and durability of our key franchises, primarily Dupixent, Libtayo, and EYLEA, and EYLEA HD. 2024 was also a year in which we made significant investments across our broad pipeline, which yielded notable progress across several key programs.

Regeneron 以強勁的第四季度為 2024 年畫上了句號，亮點是收入增長了 10%，這反映了我們主要特許經營權（主要是 Dupixent、Libtayo、EYLEA 和 EYLEA HD）的實力和持久性。 2024 年也是我們對廣泛的產品線進行大量投資的一年，並在多個關鍵項目上取得了顯著進展。

For my remarks today, I will review some of our key performance drivers, then briefly discuss a few of our more differentiated pipeline opportunities, and close with a few comments on capital allocation.

在今天的演講中，我將回顧我們的一些關鍵業績驅動因素，然後簡要討論一些更加差異化的管道機會，最後就資本配置發表幾點評論。

After my remarks, George will provide further updates on our pipeline.

在我發言之後，喬治將進一步更新我們的產品線。

Marion will then review our commercial performance, and finally, Chris will detail our financial results for the fourth quarter of 2024 and our guidance for the current year.

然後，馬里恩將回顧我們的商業表現，最後，克里斯將詳細介紹我們 2024 年第四季的財務業績和本年度的指引。

To start, I would like to share my perspective on the current state of Regeneron.

首先，我想分享一下我對 Regeneron 現況的看法。

From the beginning, our focus has been on science and innovation, developing cutting-edge technology platforms that repeatedly yield scientific breakthroughs.

從一開始，我們就專注於科學和創新，開發尖端技術平台，並持續取得科學突破。

These efforts have led to 13 products that have been approved or authorized worldwide, several of which are driving revenue growth and hold significant future potential.

這些努力已促使13種產品在全球範圍內獲得批准或授權，其中一些產品正在推動收入成長並具有巨大的未來潛力。

Our approach has already delivered five blockbuster drugs, a leading pipeline of approximately 40 product candidates across various therapeutic areas, and a world-class DNA sequence length healthcare database, providing us with unparalleled insights into key drivers of disease.

我們的方法已經帶來了五種轟動性藥物、一條涵蓋各個治療領域的約 40 種候選產品的領先產品線以及一個世界一流的 DNA 序列長度醫療保健數據庫，為我們提供了有關疾病關鍵驅動因素的無與倫比的見解。

At the JPMorgan Conference last month, we detailed 10 differentiated mid- and late-pipeline opportunities that could collectively address a total market opportunity of over $220 billion.

在上個月的摩根大通會議上，我們詳細介紹了 10 個差異化的中後期產品線機會，這些機會共同可以帶來超過 2,200 億美元的總市場機會。

Given these opportunities, the strength of our early-stage pipeline, and our turnkey technology platforms, we have never been more confident in Regeneron's future, and we are incredibly excited about what lies ahead.

鑑於這些機會、我們早期管道的實力以及我們的交鑰匙技術平台，我們對 Regeneron 的未來從未如此有信心，我們對未來的發展感到無比興奮。

Moving to our quarterly results, Dupixent continues to be a transformative medicine, with over 1 million patients on treatment around the world across seven approved indications.

從我們的季度業績來看，Dupixent 繼續成為一種變革性藥物，全球有超過 100 萬名患者在 7 種核准適應症中接受治療。

In the US, Dupixent remains the leader in new-to-brand prescription share across all of its approved indications, and continues to be well-positioned for future growth, given the potential for further penetration in approved indications, the ongoing launch in COPD, and potential 2025 launches in chronic spontaneous urticaria and Bullous pemphigoid.

在美國，Dupixent 在其所有核准適應症的新品牌處方藥份額中仍然處於領先地位，並且考慮到其在獲批適應症中的進一步滲透潛力、COPD 的持續推出以及 2025 年在慢性自發性蕁麻疹和大皰性類天皰瘡方面的潛在推出，該藥物在未來的增長方面仍然處於有利地位。

Regarding the ongoing launch in COPD, where Dupixent is the first and only biologic approved, we and our partner, Sanofi, have made great progress securing broad payer coverage and reimbursement, positioning us to drive uptake over the course of this year and beyond.

關於正在進行的慢性阻塞性肺病 (COPD) 治療藥物的上市，Dupixent 是第一個也是唯一一個獲批的生物製劑，我們和我們的合作夥伴賽諾菲在確保廣泛的付款人覆蓋和報銷方面取得了巨大進展，這使我們能夠在今年及以後推動該藥物的普及。

EYLEA HD and EYLEA continue to lead the anti-VEGF category, and our commercial efforts remain focused on driving EYLEA HD uptake, while preserving share for EYLEA in an increasingly competitive category.

EYLEA HD 和 EYLEA 繼續引領抗 VEGF 類別，我們的商業努力仍然專注於推動 EYLEA HD 的普及，同時在競爭日益激烈的類別中為 EYLEA 保持份額。

Over the course of this year, we expect continued competitive pressure on EYLEA, while strengthening the profile of EYLEA HD by offering it in a more convenient prefilled syringe administration, broadening its label to include macular edema following retinal vein occlusion, or RVO, and adding more dosing flexibility, including every four-week dosing, as well as extended dosing intervals of up to every 24 weeks for certain indications.

今年，我們預計 EYLEA 將繼續面臨競爭壓力，同時透過提供更方便的預充注射器給藥方式來加強 EYLEA HD 的形象，擴大其標籤範圍以包括視網膜靜脈阻塞或 RVO 後的黃斑水腫，並增加更多的給藥靈活性，包括每四周給藥一次，以及針對某些適應症將給藥間隔延長一次至每 24 週。

With these anticipated label enhancements, EYLEA HD will offer the broadest set of retinal disease indications with the greatest dose and flexibility of any product in the anti-VEGF category, positioning it to become the new standard of care in the category.

透過這些預期的標籤增強，EYLEA HD 將提供最廣泛的視網膜疾病適應症，並且具有抗 VEGF 類別中任何產品的最大劑量和靈活性，使其成為該類別中的新治療標準。

And we anticipate these enhancements will lead to an acceleration in EYLEA HD uptake, starting in the second half of this year.

我們預計，從今年下半年開始，這些增強功能將加速 EYLEA HD 的普及。

Leptin became Regeneron's latest blockbuster product in 2024, and we are looking to build on that by expanding shared metastatic non-melanoma skin cancers, along with making further inroads in lung cancer.

瘦素成為再生元（Regeneron）在 2024 年的最新重磅產品，我們希望在此基礎上擴大共享轉移性非黑色素瘤皮膚癌，並在肺癌領域取得進一步進展。

We also plan to seek regulatory approval for high-risk adjutant cutaneous squamous cell carcinoma, a setting in which [Kevzara] failed and over the longer term could represent a blockbuster opportunity globally in and of itself.

我們還計劃尋求監管部門對高風險輔助性皮膚鱗狀細胞癌的批准，Kevzara 在此方面失敗了，但從長遠來看，這本身可能代表著全球性的重磅機會。

Moving to our pipeline and focusing on the upcoming year, we expect regulatory approvals for Linvoseltamab in relapsed refractory multiple myeloma, odronextamab in late-line follicular lymphoma, and the aforementioned Libtayo indication in adjuvant CSCC.

轉向我們的產品線並著眼於即將到來的一年，我們預計 Linvoseltamab 用於治療復發難治性多發性骨髓瘤、odronextamab 用於治療晚期濾泡性淋巴瘤，以及前面提到的 Libtayo 用於治療輔助性 CSCC 的適應症將獲得監管部門的批准。

In addition, we expect to weed out pivotal or proof-of-concept data this year from several other programs, including our pivotal AERIFY studies for Itepekimab, our IL-33 antibody, and former smokers with COPD.

此外，我們預計今年將從其他幾個項目中篩選出關鍵或概念驗證數據，包括針對 Itepekimab、我們的 IL-33 抗體和患有 COPD 的既往吸煙者的關鍵 AERIFY 研究。

Pivotal data for the [itepekimab] Libtayo combination in first-line metastatic melanoma are also anticipated in 2024.

預計 2024 年還將獲得 [itepekimab] Libtayo 組合治療一線轉移性黑色素瘤的關鍵數據。

We also expect pivotal data for our C5 antibody siRNA combination in generalized myostatin.

我們也期待獲得有關 C5 抗體 siRNA 組合在全身肌肉生長抑制素方面的關鍵數據。

Finally, we expect to learn more about our potential opportunity to improve the quality of weight loss in obese patients on semaglutide by blocking myostatin in active RNA.

最後，我們希望進一步了解透過阻斷活性 RNA 中的肌肉生長抑制素來改善使用索馬魯肽的肥胖患者減肥品質的潛在機會。

George will soon discuss these programs in more detail and provide updates on many of the other programs in our broad and differentiated pipeline.

喬治很快將更詳細地討論這些項目，並提供我們廣泛而差異化的管道中的許多其他項目的最新動態。

Finally, regarding capital allocation, this morning we were pleased to announce the initiation of a quarterly cash dividend program and an additional $3 billion share repurchase authorization, increasing our total current buyback capacity to approximately $4.5 billion.

最後，關於資本配置，今天早上我們很高興地宣布啟動季度現金股息計劃和額外 30 億美元的股票回購授權，將我們目前的總回購能力提高到約 45 億美元。

These decisions reflect our board and management's ongoing commitment to returning capital to shareholders, but this does not change the core of our capital allocation framework.

這些決定反映了我們的董事會和管理層對向股東返還資本的持續承諾，但這不會改變我們資本配置框架的核心。

Importantly, our dividend will not impact the way we plan to heavily invest in our business and pipeline going forward, does not impair our ability to do business development in the future, and we anticipate that share repurchases will remain the primary means of returning capital to shareholders.

重要的是，我們的股利不會影響我們未來對業務和通路進行大量投資的計劃，不會損害我們未來開展業務發展的能力，而且我們預計股票回購仍將是向股東返還資本的主要方式。

However, initiating a dividend reflects our continued confidence in the future cash flows from our business, provides more balance to our approach to capital return, gives us flexibility in how we return capital in the future, and expands the pool of potential Regeneron shareholders to include funds with a dividend mandate.

然而，啟動股利反映了我們對未來業務現金流的持續信心，為我們的資本回報方式提供了更平衡的平衡，為我們未來的資本回報方式提供了靈活性，並擴大了潛在再生元股東的範圍，將具有股息授權的基金納入其中。

In closing, Regeneron remains in a very strong position scientifically, commercially, and financially, enabling us to invest heavily in R&D and deliver tremendous innovation from our pipeline, maximize the growth opportunities from our inline brands, initiate a quarterly dividend, and significantly increase our capacity to repurchase shares.

最後，Regeneron 在科學、商業和財務上仍然處於非常強大的地位，這使我們能夠在研發上投入大量資金，從我們的產品線中提供巨大的創新，最大限度地挖掘我們直列品牌的成長機會，啟動季度股息，並顯著提高我們回購股票的能力。

We look forward to keeping you updated in these innovations throughout 2025 and beyond.

我們期待在 2025 年及以後向您通報這些創新。

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

說完這些，我現在將電話轉給喬治。

Thank you, Len.

謝謝你，Len。

At last month's JPMorgan Healthcare Conference, we showcased our robust R&D efforts and the promising opportunities within our pipeline that have the potential to revolutionize the practice of medicine across several different disease areas.

在上個月的摩根大通醫療保健會議上，我們展示了我們強大的研發力量和我們產品線中的良好機遇，這些機會有可能徹底改變幾個不同疾病領域的醫療實踐。

This year holds the potential to be transformative for Regeneron, as we hope to capitalize on several of our scientific and technological breakthroughs.

今年對 Regeneron 來說具有變革的潛力，因為我們希望利用我們的多項科學和技術突破。

We anticipate reporting pivotal or proof-of-concept data from multiple programs across diverse therapeutic areas, including in oncology, COPD, and obesity, while also rapidly advancing our factor XI antibodies to multiple Phase 3 trials.

我們期待報告來自不同治療領域（包括腫瘤學、慢性阻塞性肺病和肥胖症）的多個項目的關鍵或概念驗證數據，同時也迅速推進我們的 XI 因子抗體進行多個 3 期試驗。

These programs represent significant opportunities for Regeneron to address substantial unmet needs across large commercial categories, positioning Regeneron for long-term growth.

這些項目為 Regeneron 提供了重要機遇，可滿足大型商業類別中大量未滿足的需求，為 Regeneron 的長期成長做好準備。

Let me highlight some of these opportunities and recent pipeline advancements.

讓我重點介紹其中的一些機會和最近的進展。

Starting with EYLEA HD, in December, we and Bayer reported positive data from the Phase 3 quasar study in retinal vein occlusion, where EYLEA HD demonstrated non-inferior vision gains within every eight-week dosing regimen, compared to the standard-of-care 2-milligram EYLEA dosed every four weeks.

從 EYLEA HD 開始，去年 12 月，我們和拜耳報告了視網膜靜脈阻塞第 3 期 Quasar 研究的積極數據，與每四周服用一次的標準 2 毫克 EYLEA 相比，EYLEA HD 在每八週的給藥方案中均表現出非劣效的視力增益。

Additionally, approximately 90% of EYLEA HD patients were able to maintain eight-week dosing intervals throughout the 36 weeks.

此外，大約 90% 的 EYLEA HD 患者能夠在 36 週內維持八週的給藥間隔。

These data, together with our recently presented long-term follow-up data from the PULSAR and PHOTON studies in wAMD and DME, respectively, continue to support EYLEA HD's best-in-class clinical profile.

這些數據加上我們最近分別在 wAMD 和 DME 中提出的 PULSAR 和 PHOTON 研究的長期追蹤數據，繼續支持 EYLEA HD 一流的臨床表現。

We remain on track to submit a supplementary BLA for this indication later in the first quarter.

我們將在第一季稍後針對該適應症提交補充 BLA。

We also plan to seek approval from the FDA to potentially include every four-week dosing, maximizing EYLEA HD's dosing flexibility for physicians.

我們還計劃尋求 FDA 的批准，可能包括每四周給藥一次，從而最大限度地提高 EYLEA HD 為醫生提供的給藥靈活性。

Along with the submission for a pre-filled syringe and the potential FDA approval in April to extend dosing intervals to up to 24 weeks, the longest intervals in the category, EYLEA HD is set to provide the greatest dosing flexibility across the broadest indication set of any anti-VEGF therapy, all in a convenient pre-filled syringe.

隨著預充式註射器的提交和 FDA 在 4 月批准將給藥間隔延長至 24 週（同類藥物中最長的間隔）的不斷推進，EYLEA HD 將為所有抗 VEGF 療法中最廣泛的適應症提供最大的給藥靈活性，並且全部包含在一個方便的預充式註射器中。

Next, immunology and starting with Dupixen.

接下來是免疫學，從 Dupixen 開始。

In November, Dupixen was approved in Europe to treat Eosinophilic Esophagisits in children as young as one year old, making it the first and only medicine indicated for these young patients in the US and the European Union, and further highlighting Dupixen's exceptional safety profile.

11月，Dupixen 在歐洲獲得批准，用於治療一歲以下兒童的嗜酸性食道炎，成為美國和歐盟首個也是唯一一個針對此類兒童患者的藥物，進一步凸顯了 Dupixen 卓越的安全性。

The supplementary BLA resubmission for chronic spontaneous urticaria was recently accepted by the FDA, with a target action date of April 18, potentially making it the first new target therapy for CSU in a decade.

FDA 最近接受了針對慢性自發性蕁麻疹的補充 BLA 重新提交，目標行動日期為 4 月 18 日，這可能使其成為十年來首個針對 CSU 的新型標靶療法。

Finally, a supplementary BLA was submitted for Bullous pemphigoid late last year, marking another first, as Dupixen is the only biologic to achieve significant improvements in disease remission and symptoms for this indication.

最後，在去年底提交了一份用於治療大皰性類天皰瘡的補充生物製劑許可申請，​​這又是一個第一，因為 Dupixen 是唯一一種能顯著改善該適應症的疾病緩解和症狀的生物製劑。

While Mary will discuss the ongoing launch of Dupixen in COPD, I want to remind you of another potentially significant opportunity in COPD within Apicumab, our interleukin-33 antibody discovered by Regeneron.

雖然瑪麗將討論 Dupixen 在 COPD 領域的持續上市，但我想提醒您，Apicumab（由 Regeneron 發現的我們的白細胞介素 33 抗體）在 COPD 領域還有另一個潛在的重要機會。

We anticipate reporting pivotal results in former smokers from the RF program in the second half of this year, partially over oping and distinct population from that treated with Dupixent.

我們預計將在今年下半年報告 RF 計畫對戒菸者的關鍵結果，部分結果超出接受 Dupixent 治療的人群，且與接受治療的人群截然不同。

As part of our long-term commitment to improving the lives of patients with allergic conditions, I would also like to highlight the compelling initial data from our ongoing Dupixent plus lymboceltimib trial for severe fruit allergy.

作為我們長期致力於改善過敏症患者生活的一部分，我還想強調一下我們正在進行的 Dupixent 加 lymboceltimib 治療嚴重水果過敏的試驗中令人信服的初步數據。

These two agents have the potential to eliminate immunoglobulin E or IgE, the key driver allergic reactions and prevent IgE for returning, thereby reversing severe allergies.

這兩種藥物有可能消除免疫球蛋白 E 或 IgE（引起過敏反應的主要驅動因素），並防止 IgE 復發，從而逆轉嚴重過敏。

Last month, we shared initial clinical data from the first patient in our proof-of-concept study, which showed greater than 90% reductions in both total and food specific IgE levels following initial treatments at low doses.

上個月，我們分享了概念驗證研究中第一位患者的初步臨床數據，該數據顯示，在低劑量初始治療後，整體和食物特異性 IgE 水平均降低了 90% 以上。

This trial is continuing to enroll patients, and we plan to provide updates throughout 2025.

該試驗正在繼續招募患者，我們計劃在 2025 年全年提供最新進展。

Turning now to oncology, where we continue to break new ground.

現在轉向腫瘤學，我們在該領域不斷取得新突破。

Last month, we announced positive data for Libtayo in high-risk adjuvant CSCC, becoming the first immunotherapy to show a benefit in this high-risk population.

上個月，我們公佈了 Libtayo 在高風險輔助 CSCC 中的積極數據，成為第一個在該高風險族群中顯示出益處的免疫療法。

At the first prespecified interim analysis for disease-free survival adjuvant Libtayo demonstrated a 68% reduction in the risk of disease recurrence or death compared to placebo, with no new safety signals identified.

在第一次預定的無疾病存活期中期分析中，輔助治療 Libtayo 與安慰劑相比，使疾病復發或死亡風險降低了 68%，並且沒有發現新的安全訊號。

This is the same setting in which Merck reported last year that KEYTRUDA had failed, highlighting that antibodies even within the same class, do not always produce the same treatment effect.

這與默克去年報告的 KEYTRUDA 失敗的情況相同，突顯出即使是同一類抗體，也不總是產生相同的治療效果。

We plan to submit these data to the FDA in the first half of 2025 and present these results at a medical meeting later this year.

我們計劃在 2025 年上半年向 FDA 提交這些數據，並在今年稍後的醫學會議上展示這些結果。

This data set reinforces our belief that Libtayo provides a best-in-class foundation for combinations with our other oncology assets.

這個資料集強化了我們的信念，即 Libtayo 為與我們其他腫瘤學資產的結合提供了一流的基礎。

Data from early clinical trials in melanoma suggests that [Fianlimab] our Lag-3 antibody, when combined with Libtayo might be the first combination to demonstrate meaningful additive benefit compared to PD-1 monotherapy without exacerbating safety.

來自黑色素瘤早期臨床試驗的數據表明，我們的 Lag-3 抗體 [Fianlimab] 與 Libtayo 結合使用，可能是第一個與 PD-1 單藥療法相比顯示出有意義的附加益處且不會加劇安全性的組合。

This combination is being studied in an ongoing randomized Phase 3 trial versus KEYTRUDA monotherapy in first-line metastatic melanoma, with results expected in the second half of this year.

目前正在進行一項隨機 3 期臨床試驗，研究該組合療法與 KEYTRUDA 單藥治療一線轉移性黑色素瘤的效果，預計結果將在今年下半年公佈。

If these data confirm best-in-class activity in melanoma, it will increase our confidence for this combination in other cancer settings.

如果這些數據證實了黑色素瘤中的最佳活性，它將增加我們對其他癌症環境中這種組合的信心。

Turning to our CD3 bispecifics.

轉向我們的 CD3 雙特異性抗體。

We are pleased to announce that we have recently resubmitted the BLA for linvoseltamab, or BCMA by CD3 bispecific for relapsed refractory multiple myeloma following the resolution of third-party manufacturing issues.

我們很高興地宣布，在第三方製造問題解決後，我們最近重新提交了林沃司他單抗（或 BCMA by CD3 雙特異性抗體）用於治療復發難治性多發性骨髓瘤的 BLA。

Linvoseltamab has the potential to be the best-in-class BCMA by CD3 bispecific due to its differentiated clinical profile, dosing and administration with nearly double the reported complete response rates at similar duration of follow-up.

Linvoseltamab 具有成為同類最佳 BCMA CD3 雙特異性抗體的潛力，因為它具有差異化的臨床特徵、劑量和給藥方式，在相似的隨訪時間內其完全緩解率幾乎是報告的兩倍。

Given the strength of the data in late lines of therapy, including the observed level of efficacy and favorable safety profile of lumoseltimab, we are pursuing a differentiated approach in earlier lines of therapy emphasizing monotherapy and novel limited combination approaches.

鑑於後期治療數據的強度，包括觀察到的 lumoseltimab 的療效水平和良好的安全性，我們正在早期治療中採取差異化方法，強調單一療法和新的有限組合療法。

For odronextamab, our CD20 x CD3 bispecific we are pleased to announce that we have resubmitted the BLA for relapsed refractory follicular lymphoma where odronextamab has also demonstrated potentially best-in-class efficacy, and we expect an FDA decision in the second half of 2025.

對於我們的 CD20 x CD3 雙特異性藥物 odronextamab，我們很高興地宣布，我們已經重新提交了復發難治性濾泡性淋巴瘤的 BLA，其中 odronextamab 也表現出了潛在的最佳療效，我們預計 FDA 將在 2025 年下半年做出決定。

In December, at the American Society of Hematology meeting, we presented initial results from the safety lead-in portion of the confirmatory Phase 3 OLYMPIA trial.

12 月，在美國血液學會會議上，我們展示了確認性 3 期 OLYMPIA 試驗安全性引導部分的初步結果。

Odronextamab monotherapy delivered complete responses in all 12 patients evaluable for efficacy with previously untreated follicular lymphoma.

Odronextamab 單藥療法使所有 12 名可評估療效的未曾治療的濾泡性淋巴瘤患者均獲得完全緩解。

As a reminder, the standard of care regimen in this setting, rituximab plus chemotherapy has historically achieved complete responses in approximately 67% of patients.

需要提醒的是，在這種情況下，標準治療方案是利妥昔單抗合併化療，歷史上約有 67% 的患者獲得了完全緩解。

Based on this impressive monotherapy efficacy for odronextamab in both late line and first-line patients we are once again exploring a differentiated program in early lines of therapy, highlighted our head-to-head evaluation of odronextamab monotherapy compared to Rituxan plus chemotherapy in our Phase 2 OLYMPIA 1 trial, which has already achieved over 40% enrollment.

基於 odronextamab 在晚期和一線患者中均表現出的令人印象深刻的單藥治療效果，我們再次探索早期治療中的差異化方案，重點介紹了我們在第 2 階段 OLYMPIA 1 試驗中對 odronextamab 單藥治療與 Rituxan 加化療進行的頭對頭評估，該試驗的入組率已超過 40%。

Our CD28 costimulatory bispecifics for solid tumors are also progressing.

我們針對實體腫瘤的CD28共刺激雙特異性抗體也正在取得進展。

We're working to mitigate safety concerns related to their combination with PD-1 blockade while prioritizing combination with CD3 bispecifics.

我們正在努力減輕它們與 PD-1 阻斷劑結合相關的安全問題，同時優先考慮與 CD3 雙特異性抗體的結合。

The science suggests that this approach may enhance efficacy with fewer immune-mediated adverse events.

科學表明，這種方法可以提高療效，並減少免疫介導的不良事件。

We will provide updates on these innovative combinations later this year.

我們將在今年稍後提供有關這些創新組合的最新消息。

Moving now to a rapidly advancing Factor XI program.

現在轉向快速推進的 XI 因子計劃。

We're employing a two-pronged approach to anticoagulation that offers a potential for improved blood prevention and lower bleeding risk supported by genetic data from the Regeneron Genetics Center our approach has delivered two antibodies with unique profile to meet different market needs.

我們採用雙管齊下的抗凝血方法，有可能改善血液預防並降低出血風險，並在再生元遺傳中心的遺傳數據的支持下，我們的方法提供了兩種具有獨特特徵的抗體，以滿足不同的市場需求。

Regeneron 708, which targets the catalytic domain of Factor XI may provide improved efficacy compared to standard of care options.

Regeneron 708 針對的是因子 XI 的催化域，與標準治療方案相比，可能提供更高的療效。

Offering patients who need significant anticoagulation activity, a potentially more effective option.

為需要顯著抗凝血治療的患者提供潛在更有效的選擇。

On the other hand, ReGeN-9933, which targets the two domain is expected to carry a lower risk of bleeding.

另一方面，針對這兩個結構域的 ReGeN-9933 預計出血風險較低。

Potentially making it a viable option for patients with the highest bleeding risk who would otherwise not be candidates for currently available anticoagulants.

對於那些出血風險最高、原本不適合使用目前可用的抗凝血劑的患者來說，這可能使其成為可行的選擇。

Late this year, we reported positive proof-of-concept data with the prevention of venous thromboebulism following total knee replacement with both antibodies demonstrating robust antiserobotic effects, Regeneron 7508 was superior to enoxaparin and non-inferior pixaban, while ReGen-9933 was numerically better than

今年晚些時候，我們報告了積極的概念驗證數據，顯示兩種抗體在預防全膝關節置換術後靜脈血栓形成方面均表現出強大的抗血清作用，Regeneron 7508 優於依諾肝素且不遜於 pixaban，而 ReGen-9933 在數值上優於

[Enoxaparin].

[依諾肝素]。

These data support the advancement of both antibodies into broad pivotal programs across multiple indications and patient types with initial Phase 3 studies expected to begin enrolling this year.

這些數據支持將這兩種抗體推進到涵蓋多種適應症和患者類型的廣泛關鍵項目中，初步的 3 期研究預計將於今年開始招募。

Moving briefly to obesity, where we are progressing early clinical programs and an expansive pipeline of preclinical assets.

簡單談談肥胖症，我們正在推動早期臨床計畫和廣泛的臨床前資產管線。

Our muscle-sparing Phase 2 COURAGE study is investigating the addition of tezivogrimab to semaglutide with and without garatizumab to improve the quality of weight loss and evaluate the maintenance of weight loss after discontinuing semaglutide.

我們的保留肌肉的 2 期 COURAGE 研究正在研究在索馬魯肽中添加 tezivogrimab，同時聯合或不聯合加拉珠單抗，以改善減肥質量，並評估停用索馬魯肽後減肥效果的維持情況。

This trial is fully enrolled with data expected in the second half of the year.

此項試驗目前已全部招募完畢，預計今年下半年將取得數據。

Moving to our Regeneron Genetics medicine pipeline, starting with our differentiated siRNA plus antibody approach.

轉向我們的再生元遺傳學藥物管道，從我們的差異化 siRNA 加抗體方法開始。

We have a potential to address multiple complement-mediated diseases.

我們有潛力治療多種補體介導的疾病。

In December, at the ASH Annual Meeting, we presented compelling updated results from an exploratory cohort in our Phase 3 program for paroxysmal lateral hemoglobin urea.

12 月，在 ASH 年會上，我們展示了陣發性側血紅蛋白尿素 III 期計劃中探索性隊列的令人信服的最新結果。

Our combination achieved greater disease control compared to the standard current of care, ravulizumab and only our combination lowered mean LDH levels to the normal range.

與目前的標準治療方法 ravulizumab 相比，我們的組合療法取得了更好的疾病控制效果，並且只有我們的組合療法將平均 LDH 水平降低到正常範圍。

When ravulizumab patients were switched to our combination, their mean LDH levels, which remained higher than normal, also became normalized.

當 ravulizumab 患者轉而接受我們的聯合治療時，他們的平均 LDH 水平（之前仍然高於正常值）也恢復正常。

We are also evaluating this combination in generalized myasthenia gravis with pivotal results expected in the second half of this year.

我們也正在評估這種組合療法在治療全身性重症肌無力方面的療效，預計今年下半年獲得關鍵結果。

In addition, we recently initiated our Phase 3 program exploring this combination in geographic atrophy in dry age-related macrodegeneration where we believe our systemic approach has several advantages over currently approved intravitreal agents.

此外，我們最近啟動了第 3 階段計劃，探索這種組合在乾性老年性大變性地圖樣萎縮中的應用，我們相信我們的系統方法比目前批准的玻璃體內藥物有幾個優勢。

For DB-OTO, our autoferilin gene therapy program for genetic hearing loss, we announced data last month from the ongoing clinical program, [ DB ] OTO is an AAV-based dual vector gene therapy delivered to the inner ear to enable hearing and children suffering from profound genetic hearing deficit.

對於 DB-OTO，即我們針對遺傳性聽力損失的自體營養素基因治療項目，我們上個月公佈了正在進行的臨床項目的數據，[DB]OTO 是一種基於 AAV 的雙載體基因療法，輸送到內耳，以恢復聽力並幫助患有嚴重遺傳性聽力缺陷的兒童。

We reported that 10 out of 11 treated children with at least one post-treatment assessment showed a notable increase in hearing with some reaching the normal range.

我們報告稱，接受治療的 11 名兒童中，有 10 名至少進行過一次治療後評估，其聽力明顯提高，有些甚至達到了正常範圍。

We look forward to continuing to share additional data later this year.

我們期待今年稍後繼續分享更多數據。

Regarding our collaboration with Alnylam, we are advancing several new siRNA CNS programs, including synuclein for Parkinson's and tau for Alzheimer's and other neurodegenerative diseases with trials initiating later this year.

關於我們與 Alnylam 的合作，我們正在推進幾個新的 siRNA CNS 項目，包括用於治療帕金森氏症的突觸核蛋白和用於治療阿茲海默症和其他神經退化性疾病的 tau，試驗將於今年稍後開始。

And finally, I would like to highlight two recent advances that extend our leadership position in the field of structured big data that will be necessary to allow computational approaches to revolutionize the health care industry.

最後，我想強調一下最近的兩項進展，這兩項進展擴大了我們在結構化大數據領域的領導地位，這對於計算方法徹底改變醫療保健產業是必要的。

Over the past decade, we have become the leader in high-throughput human DNA sequencing, enabling us to create the world's largest G&A sequence linked health care database, encompassing nearly 3 million individuals, all with DNA sequence linked to de-identified health care records.

在過去的十年中，我們已經成為高通量人類 DNA 定序領域的領導者，這使我們能夠創建世界上最大的 G&A 序列連結醫療保健資料庫，該資料庫涵蓋近 300 萬人，所有個人的 DNA 序列都與匿名醫療保健記錄相關聯。

We are now emerging also as the leaders in high-throughput proteomics, as reflected by the selection of the Regeneron Genetic Center to generate the proteomics data for the UK Biobank pharma proteomics project, building on our previous selection to provide the sequence data for the UK Biobank.

我們現在也正在成為高通量蛋白質組學領域的領導者，這一點從我們選擇再生元基因中心為英國生物銀行製藥蛋白質組學計畫生成蛋白質組學數據可以看出，此前我們已選擇為英國生物銀行提供序列數據。

Importantly, our new strategic collaboration with Truveta is expected to dramatically expand our database to include up to an additional 10 million individuals from Truveta's network of leading US health system with the opportunity to generate both DNA sequence and proteomics information.

重要的是，我們與 Truveta 的新策略合作預計將大幅擴展我們的資料庫，將來自 Truveta 領先的美國醫療系統網絡的多達 1000 萬個人納入其中，並有機會產生 DNA 序列和蛋白質組學資訊。

While our leadership position in this big data space has already proven invaluable for our drug discovery and development efforts we believe it can ultimately help us contribute to revolutionizing the field of health care analytics and management.

雖然我們在這個大數據領域的領導地位已經證明對我們的藥物發現和開發工作具有不可估量的價值，但我們相信它最終可以幫助我們為醫療分析和管理領域的革命性變革做出貢獻。

In summary, I have never been more excited about the future of Regeneron and our potential to transform the practice of medicine and revolutionize the health care industry.

總而言之，我從未像現在這樣對 Regeneron 的未來以及我們改變醫療實踐和革命性醫療保健行業的潛力感到興奮。

Our pipeline is more innovative and exciting than ever, and we anticipate several pivotal or proof-of-concept data readouts throughout 2025, positioning Regeneron for long-term success.

我們的產品線比以往任何時候都更具創新性和令人興奮，我們預計在 2025 年將會有幾次關鍵或概念驗證數據讀數，為 Regeneron 的長期成功做好準備。

Let me now turn the call over to Marion.

現在讓我把電話轉給馬里恩。

Thank you, George.

謝謝你，喬治。

Regeneron's fourth quarter performance demonstrates our ongoing leadership across therapeutic categories.

Regeneron 第四季的業績證明了我們在治療領域的持續領導地位。

Our commercial team is well positioned to optimize our 2025 growth opportunities driven by new indications, new product enhancements and new product approvals.

我們的商業團隊已做好準備，透過新的適應症、新產品的增強和新產品的批准，充分利用我們 2025 年的成長機會。

Turning to fourth quarter results, starting with EYLEA HD and EYLEA.

談到第四季度的業績，首先從 EYLEA HD 和 EYLEA 開始。

In January, we announced combined fourth quarter US net sales of $1.5 billion for EYLEA HD and EYLEA capturing over 46% of the total anti-VEGF category.

今年 1 月，我們宣布 EYLEA HD 和 EYLEA 在美國第四季的淨銷售額總計達 15 億美元，佔抗 VEGF 類藥物總銷售額的 46% 以上。

For the full year, net product sales grew by 1.4% to approximately $6 billion despite increasing competition in the category.

儘管該類別的競爭日益激烈，但全年淨產品銷售額仍成長了 1.4%，達到約 60 億美元。

EYLEA HD net sales were $305 million in the fourth quarter and $1.2 billion for the full year, representing 20% of the combined net sales for LHD and EYLEA.

EYLEA HD 第四季淨銷售額為 3.05 億美元，全年淨銷售額為 12 億美元，佔 LHD 和 EYLEA 合併淨銷售額的 20%。

Fourth quarter net sales for EYLEA HD were affected by elevated wholesaler inventory levels at the end of Q3, which were absorbed over the course of the fourth quarter.

EYLEA HD 第四季的淨銷售額受到第三季末批發商庫存水準上升的影響，這些庫存在第四季度被吸收。

In 2025, our team is laser-focused on growing EYLEA HD adoption.

2025 年，我們的團隊將專注於擴大 EYLEA HD 的採用。

Physicians tell us that EYLEA HD has the potential to be the new standard of care for retinal diseases and several catalysts occurring this year will put us in a position to grow our competitive share.

醫生告訴我們，EYLEA HD 有可能成為視網膜疾病治療的新標準，今年發生的幾種催化劑將使我們處於擴大競爭份額的位置。

The team is ready to launch the prefilled syringe and our two-year label updates, both of which are anticipated to occur in the second quarter.

團隊已準備好推出預充式註射器和我們的兩年標籤更新，預計這兩項更新都將在第二季進行。

Physicians easily await the prefilled syringe, which has been described as being changing by clinical trial participants.

醫生很容易等待預充式註射器，臨床試驗參與者形容它正在改變。

Further, our two-year long-term follow-up data from the PULSAR PHOTON studies in wAMD and DME, respectively, clearly illustrate EYLEA HD's ability to extend dosing beyond any other competitor in the anti-VEGF category.

此外，我們分別在 wAMD 和 DME 中從 PULSAR PHOTON 研究中獲得的兩年長期追蹤數據清楚地表明了 EYLEA HD 延長給藥的能力超越了抗 VEGF 類別中的任何其他競爭對手。

Two other potential FDA approvals are also expected later this year, the RVO indication and additional dosing flexibility.

FDA 預計今年稍後還將批准另外兩項藥物，即 RVO 適應症和額外的劑量靈活性。

In RVO clinical trials, EYLEA HD dosing could be extended to every 12 weeks following loading doses making it the only medicine with durability beyond 4 weeks and also the only medicine to show a numeric improvement and vision for RVO patients compared to EYLEA dosed every 4 weeks.

在 RVO 臨床試驗中，EYLEA HD 給藥可以在負荷劑量後延長至每 12 週一次，使其成為唯一具有超過 4 週持久性的藥物，也是唯一與每 4 週給藥一次的 EYLEA 相比，顯示 RVO 患者在數值上得到改善並改善視力的藥物。

In terms of additional dosing flexibility across all of our approved indications, we look forward to the potential FDA approval of every 4-week dosing for the subset of patients who need it which would mean EYLEA HD has the most flexible dosing schedule of any anti-VEGF medicine.

在我們所有核准適應症的額外給藥靈活性方面，我們期待 FDA 批准對有需要的患者亞群進行每 4 週一次的給藥，這意味著 EYLEA HD 擁有所有抗 VEGF 藥物中最靈活的給藥時間表。

Fourth quarter EYLEA net sales were $1.2 billion, primarily driven by persistent physician demand in spite of a recent aflibercept 2-milligram biosimilar launch, wholesale inventory levels were elevated at the end of the fourth quarter, and we expect EYLEA net sales will be negatively impacted in the first quarter of 2025 as this increase in inventory is absorbed.

第四季 EYLEA 淨銷售額為 12 億美元，主要受持續的醫生需求推動，儘管最近推出了 2 毫克阿柏西普生物仿製藥，但第四季度末批發庫存水平有所上升，我們預計，隨著庫存增加被吸收，EYLEA 淨銷售額將在 2025 年第一季度受到負面影響。

We also expect ongoing market dynamics will put downward pressure on EYLEA business.

我們也預期持續的市場動態將對 EYLEA 業務造成下行壓力。

We continue supporting existing and new patients who benefit from EYLEA while prioritizing uptake of EYLEA HD, which has the clinical profile to potentially become the new standard of care in the anti-VEGF category.

我們將繼續支持受益於 EYLEA 的現有和新患者，同時優先考慮採用 EYLEA HD，其臨床特徵有可能成為抗 VEGF 類別的新治療標準。

Turning now to Libtayo, which achieved blockbuster status in 2024 with global net sales of $1.2 billion.

現在來看看 Libtayo，它在 2024 年獲得了轟動的地位，全球淨銷售額達到 12 億美元。

In the fourth quarter, global net sales grew by 50% year-over-year to $367 million with US net sales reaching $251 million.

第四季度，全球淨銷售額年增50%至3.67億美元，其中美國淨銷售額達2.51億美元。

Libtayo's strong performance was based on growth in non-melanoma skin cancers and steady gains in lung cancer.

Libtayo 的強勁表​​現基於非黑色素瘤皮膚癌的增長和肺癌的穩定增長。

Looking forward, we eagerly await the submission and potential approval of Libtayo in high-risk adjuvant CSCC beginning in the US, where we estimate there are approximately 10,000 patients who may benefit from treatment.

展望未來，我們熱切期待 Libtayo 在美國提交並獲批用於治療高風險輔助 CSCC，我們估計美國約有 10,000 名患者可能從治療中受益。

And next to Dupixent, which continues to deliver exceptional results in type 2 inflammatory diseases, approved in seven indications worldwide, more than 1 million patients are currently benefiting from Dupixent treatment.

Dupixent 在 2 型發炎疾病領域持續取得卓越成果，已在全球 7 種適應症中獲得批准，目前已有超過 100 萬名患者正在受益於 Dupixent 治療。

Three of these indications, atopic dermatitis, asthma and nasal polyps have achieved blockbuster status each generating over $1 billion in annual net sales.

其中三種治療異位性皮膚炎、氣喘和鼻息肉的藥物已獲得轟動性地位，每種藥物的年淨銷售額均超過 10 億美元。

In the fourth quarter, Dupixent worldwide net sales grew 15% year-over-year to $3.7 billion with increasing volume across all indications, age groups and geographies.

第四季度，Dupixent 全球淨銷售額年增 15% 至 37 億美元，所有適應症、年齡層和地區的銷量均有所增長。

In the US, net sales grew 10% year-over-year to $2.7 billion, driven by a 24% increase in total prescriptions including the recent COPD launch.

在美國，淨銷售額年增 10% 至 27 億美元，這得益於包括最近推出的 COPD 藥物在內的總處方量增加 24%。

As Sanofi noted, fourth quarter results were negatively impacted by onetime items.

賽諾菲指出，第四季的業績受到一次性項目的負面影響。

We continue to see broad growth across all blockbuster indications of atopic dermatitis, asthma and nasal polyps, despite new entrants and atopic dermatitis, Dupixent continues to be first choice for physicians who now understand that IL-4 and IL-13 are crucial drivers of type 2 inflammation.

我們繼續看到異位性皮膚炎、氣喘和鼻息肉等所有重磅適應症的廣泛增長，儘管出現了新進入者和異位性皮膚炎，但 Dupixent 仍然是醫生的首選，他們現在了解到 IL-4 和 IL-13 是 2 型發炎的關鍵驅動因素。

Additionally, there is robust uptake in our recent US launches for cenozoic esophagitis, [Pragagilaris] with current trends suggesting that these indications will likely also achieve blockbuster status.

此外，我們最近在美國推出的治療新生代食道炎的藥物[Pragagilaris] 也獲得了強勁的市場需求，目前的趨勢表明這些適應症也可能獲得重磅藥物的地位。

We are off to a promising start in COPD, following approvals in more than 30 countries.

繼獲得 30 多個國家的批准後，我們在 COPD 領域取得了良好的開端。

In the US, the FDA approved Dupixent in September of last year, and we are very encouraged by our progress in early market adoption Together with our partner, Sanofi, we've made significant strides in securing US access and reimbursement for commercial and Medicare patients.

在美國，FDA 於去年 9 月批准了 Dupixent，我們對早期市場採用方面取得的進展感到非常鼓舞，我們與合作夥伴賽諾菲一起，在確保美國商業和醫療保險患者能夠獲得該藥物並獲得報銷方面取得了重大進展。

At the start of this year, nearly 85% of commercial patients and nearly 90% of Medicare patients have coverage.

今年年初，近 85% 的商業患者和近 90% 的醫療保險患者都獲得了保險。

Additionally, we are pleased that global gold treatment guidelines for COPD now include Dupixent as the only recommended biologic medicine for these patients.

此外，我們很高興看到，全球慢性阻塞性肺病黃金治療指南現已將 Dupixent 列為該類患者唯一推薦的生物藥物。

We look forward to accelerating the launch of this important indication and to make a significant difference in the lives of hundreds of thousands of COPD patients worldwide.

我們期待加速這項重要適應症的推出，並為全球數十萬名慢性阻塞性肺病患者的生活帶來重大改變。

Our teams are also preparing for a potential April launch in chronic spontaneous urticaria pending FDA approval, we believe Dupixent offers a compelling treatment option and if approved, would be the first new targeted therapy in the US in over a decade for the estimated 300,000 CSU patients.

我們的團隊也準備在 4 月推出用於治療慢性自發性蕁麻疹的藥物，等待 FDA 批准，我們相信 Dupixent 提供了一種引人注目的治療選擇，如果獲得批准，它將成為美國十多年來針對估計 30 萬名 CSU 患者的首個新型靶向治療方法。

In conclusion, we continued to deliver solid performance across our commercial portfolio in the fourth quarter.

總之，我們的商業投資組合在第四季持續保持穩健的表現。

We also see significant growth opportunities in 2025 and beyond with near and medium-term catalysts to drive growth.

我們也看到 2025 年及以後存在巨大的成長機會，並有短期和中期催化劑來推動成長。

With that, I'll turn the call to Chris.

說完這些，我就把電話轉給克里斯。

Thank you, Marion.

謝謝你，瑪麗安。

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

除非另有說明，我今天對 Regeneron 財務業績和前景的評論將基於非 GAAP 基礎。

Regeneron ended 2024 with strong financial performance in the fourth quarter, delivering growth on both the top and bottom line.

2024 年底，Regeneron 第四季財務表現強勁，營收和利潤均成長。

Total revenues grew 10% year-over-year to $3.8 billion, primarily reflecting higher Sanofi collaboration revenue driven by Dupixent growth and strong global net sales growth for Libtayo and modest growth for combined net sales of EYLEA HD and EYLEA in the US.

總營收年增 10% 至 38 億美元，主要反映了賽諾菲合作收入的增加，這得益於 Dupixent 的成長、Libtayo 的強勁全球淨銷售額成長以及 EYLEA HD 和 EYLEA 在美國綜合淨銷售額的溫和成長。

Fourth quarter diluted net income per share was $12.07 on net income of $1.4 billion, up 2% from the prior year.

第四季每股攤薄淨利潤為 12.07 美元，淨利潤為 14 億美元，較上年增長 2%。

On a full year basis, total revenues were $14.2 billion, representing growth of 10% when excluding revenues from Ronapreve. 2024 earnings per share grew 4% from the prior year to $45.2.

全年總收入為 142 億美元，不包括 Ronapreve 的營收則成長了 10%。 2024年每股收益較上年增長4%至45.2美元。

Turning to collaboration revenue in the fourth quarter.

轉向第四季的合作收入。

Revenues from the Sanofi collaboration were $1.2 billion, of which $1 billion related to our share of collaboration profits.

賽諾菲合作計畫的收入為 12 億美元，其中 10 億美元與我們分享的合作利潤有關。

Regeneron's share of profits grew 18% versus the prior year driven by volume growth for Dupixent and higher collaboration margins.

由於 Dupixent 的銷售成長和合作利潤率的提高，Regeneron 的利潤份額較上年增長了 18%。

For the year, our share of profit, net of development balance reimbursement increased to the highest level since initiation of the collaboration, reaching approximately 20% of of total antibody net sales.

本年度，我們扣除開發餘額補償後的利潤份額增至合作開始以來的最高水平，達到抗體淨銷售額總額的約 20%。

The Sanofi development balance was approximately $1.6 billion at the end of 2024, reflecting a reduction of approximately $175 million from the end of the third quarter and approximately $700 million from the end of 2023.

2024 年底賽諾菲開發餘額約 16 億美元，較第三季末減少約 1.75 億美元，較 2023 年底減少約 7 億美元。

We continue to expect this balance to be fully reimbursed by the end of 2026 which is expected to result in a significant increase in Sanofi collaboration revenue and cash flow thereafter.

我們繼續預計該餘額將在 2026 年底前全額償還，預計這將導致賽諾菲合作收入和現金流大幅增加。

Moving to Bayer.

轉向拜耳。

Fourth quarter ex US net sales of EYLEA and EYLEA 8-Mig were $888 million, up 2% on a constant currency basis versus the prior year.

第四季度，EYLEA 和 EYLEA 8-Mig 的美國以外淨銷售額為 8.88 億美元，以固定匯率計算較上年增長 2%。

Total buyer collaboration revenue was $377 million, of which $349 million related to our share of net profits outside the US.

買家合作總收入為 3.77 億美元，其中 3.49 億美元與我們在美國以外的淨利潤份額有關。

Now to our operating expenses.

現在談談我們的營運費用。

R&D expense was $1.2 billion in the fourth quarter.

第四季研發費用為12億美元。

The increase in R&D expense versus the prior year was driven by cost to support advancement of Regeneron's broad clinical pipeline, including our C5 and Factor XI programs in hematology, certain oncology programs, itepekimab in COPD and our ongoing program in obesity.

與前一年相比，研發費用的增加是由於支持 Regeneron 廣泛臨床管線進展的成本，包括血液學中的 C5 和因子 XI 計畫、某些腫瘤學計畫、COPD 中的 itepekimab 以及我們正在進行的肥胖症計畫。

Fourth quarter SG&A was $681 million, with growth from the prior year, primarily reflecting investments to support the launch of EYLEA HD and our international expansion.

第四季銷售、一般及行政開支為 6.81 億美元，較上年有所成長，主要反映了對支持 EYLEA HD 推出和國際擴張的投資。

Fourth quarter 2024 gross margin on net product sales was 86%, up slightly from the prior year quarter.

2024 年第四季淨產品銷售毛利率為 86%，較去年同期略有上升。

Now to cash flow and the balance sheet.

現在討論現金流和資產負債表。

Regeneron generated approximately $3.7 billion in free cash flow in 2024 and ended the year with cash and marketable securities less debt of approximately $15.2 billion.

2024 年，Regeneron 產生了約 37 億美元的自由現金流，年底的現金和有價證券減去債務約 152 億美元。

In 2024, we deployed $2.6 billion towards share repurchases, including a meaningful step-up in the fourth quarter, during which we repurchased nearly $1 billion of our shares.

2024 年，我們部署了 26 億美元用於股票回購，其中第四季的回購金額顯著增加，回購了近 10 億美元的股票。

Consistent with our capital allocation framework, we are investing heavily in our R&D capabilities to drive long-term growth, exploring business development opportunities and returning capital to shareholders.

根據我們的資本配置框架，我們正在大力投資研發能力，以推動長期成長、探索業務發展機會並向股東返還資本。

This morning, we announced an additional share repurchase authorization of $3 billion, increasing our capacity for repurchases to approximately $4.5 billion as of today.

今天上午，我們宣布了額外 30 億美元的股票回購授權，截至今天，我們的回購能力增加到約 45 億美元。

In addition, we are enhancing our approach to returning capital to shareholders.

此外，我們正在加強向股東返還資本的方式。

As announced this morning, our Board of Directors has authorized the initiation of a quarterly dividend with the first dividend payable on March 20 and to shareholders of record as of February 20.

正如今天早上宣布的那樣，我們的董事會已批准開始季度股息，第一筆股息將於 3 月 20 日支付給截至 2 月 20 日登記在冊的股東。

The dividend will be $0.88 per share, equivalent to $3.52 per share on an annual basis.

股息為每股 0.88 美元，相當於年度每股 3.52 美元。

We are confident in the long-term growth of our business, our innovative R&D engine, our differentiated pipeline and the durability of our cash flows, all of which support the initiation of our first quarterly dividend and the announcement of an additional share repurchase authorization.

我們對業務的長期成長、創新的研發引擎、差異化的產品線和現金流的持久性充滿信心，所有這些都支持我們啟動第一季股息並宣布額外的股票回購授權。

I'll conclude with a review of our 2025 financial guidance.

最後，我將回顧我們的 2025 年財務指引。

We expect 2025 R&D spend to be in the range of $5 billion to $5.2 billion.

我們預計 2025 年研發支出將在 50 億美元至 52 億美元之間。

The increase versus 2024 is driven by cost to support our expanding late-stage pipeline including Phase 3 programs for our Factor XI antibodies and hemoc bispecifics as well as programs in obesity and genetic medicines and the advancement of multiple new assets into the clinic.

與 2024 年相比的成長主要是由於支持我們不斷擴大的後期產品線的成本，包括第 XI 因子抗體和 hemoc 雙特異性抗體的 3 期計劃、肥胖症和基因藥物計劃以及多種新資產進入臨床階段的進展。

We expect 2025 SG&A to be in the range of $2.55 billion to $2.7 billion, representing 3% growth at the midpoint of this range versus 2024, driven by investments to support multiple potential oncology launches.

我們預計 2025 年銷售、一般及行政費用將在 25.5 億美元至 27 億美元之間，與 2024 年相比，增長 3%，這主要得益於對多個潛在腫瘤學產品上市的支持投資。

We expect our gross margin on net product sales to be in the range of 87% to 88%.

我們預計淨產品銷售毛利率在 87% 至 88% 之間。

This guidance reflects a change in product mix as well as ongoing start-up costs for our new fill finish facility and investments to drive future efficiencies across our manufacturing network.

該指引反映了產品結構的變化以及我們新灌裝設施的持續啟動成本和推動整個製造網路未來效率的投資。

We expect cost of collaboration manufacturing to be in the range of $1 billion to $1.15 billion in 2025 and primarily driven by higher Dupixent volumes.

我們預計，到 2025 年，協作製造成本將在 10 億美元至 11.5 億美元之間，這主要受 Dupixent 產量增加的推動。

Recall that we are reimbursed for these costs as revenue, making them generally neutral to net income.

回想一下，我們以收入的形式補償這些成本，這使得它們對淨收入通常沒有影響。

We expect 2025 capital expenditures to be in the range of $850 million to $975 million, primarily related to ongoing expansion of the R&D facilities at our Tarrytown headquarters and investments to increase both manufacturing capacity in the US and Ireland to support our expanding pipeline.

我們預計 2025 年的資本支出將在 8.5 億美元至 9.75 億美元之間，主要用於持續擴建位於 Tarrytown 總部的研發設施以及投資增加美國和愛爾蘭的製造能力，以支持我們不斷擴大的產品線。

Finally, we expect our 2025 effective tax rate to be in the range of 11% to 13%.

最後，我們預計 2025 年的有效稅率將在 11% 至 13% 之間。

In summary, Regeneron delivered solid financial results in 2024 and our strong financial position and prudent capital allocation enables Regeneron to deliver long-term shareholder value.

總而言之，Regeneron 在 2024 年取得了穩健的財務業績，我們強大的財務狀況和審慎的資本配置使 Regeneron 能夠實現長期股東價值。

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

說完這些，我就把電話轉回給瑞安。

Thanks, Chris.

謝謝，克里斯。

This concludes our prepared remarks.

我們的準備好的演講到此結束。

We will now open the call for Q&A to ensure we were able to address as many questions as possible.

我們現在將開始問答環節，以確保我們能夠解答盡可能多的問題。

We will answer only one question from each caller before moving to the next.

我們將只回答每個來電者的一個問題，然後再回答下一個問題。

Towanda, can you go to the first question, please?

托旺達，您能回答第一個問題嗎？

(Operator Instructions) Our first question comes from the line of Brian Abrahams.

（操作員指示）我們的第一個問題來自 Brian Abrahams。

Your line is open.

您的線路已開通。

Hey, guys.

嘿，大家好。

Good morning.

早安.

Thanks for taking my question.

感謝您回答我的問題。

Consensus numbers suggest expectations for annual sales erosion of about 7% annually over the next few years for the EYLEA franchise.

一致數據顯示，未來幾年 EYLEA 特許經營的年銷售額預計每年將下降約 7%。

Just given what you've been seeing on the ground and some of the dynamics you described, including competitive pressure, but a potential acceleration in HD with some of those approvals, do you think that these expectations look reasonable?

鑑於您在實地看到的情況和您所描述的一些動態，包括競爭壓力，但隨著一些批准，高清業務可能會加速發展，您認為這些預期合理嗎？

And I know you guys don't typically provide guidance, but I just -- I think any directionality might be helpful here.

我知道你們通常不會提供指導，但我只是——我認為任何方向性都可能有所幫助。

Just to understand whether folks are looking at dynamics here the right way or if expectations may be way off?

只是想了解人們是否以正確的方式看待這裡的動態，或者預期可能相差甚遠？

So as you pointed out, we don't give guidance.

正如您所指出的，我們不提供指導。

I wanted to give you a summary today of how we see the market and certainly, as it relates to EYLEA HD and the strengthening of the profile that we hope with additional FDA approvals this year related to delivery system with the prefilled syringe, indication with RVO, dosing flexibility and then also the clinical data that further cements EYLEA HD as the product with the greatest durability -- we believe that combination of factors for EYLEA HD and the fact that already in our year -- this past year in the market, EYLEA HD at $1.2 billion in net sales is a blockbuster product

今天，我想給大家總結一下我們對市場的看法，當然，這與 EYLEA HD 有關，我們希望今年能獲得 FDA 的更多批准，包括預充式註射器的輸送系統、RVO 適應症、劑量靈活性，以及​​進一步鞏固 EYLEA HD 作為最耐用產品的臨床數據。

.

。

We see that as a very compelling profile.

我們認為這是一個非常引人注目的形象。

But I did want to be very realistic in my comments indicated, we do expect to see additional competitive pressure on EYLEA.

但我在我的評論中確實希望非常現實，我們確實預計 EYLEA 將面臨額外的競爭壓力。

Obviously, there's a biosimilar in the market today.

顯然，目前市場上存在生物相似藥。

So that is a factor that needs to be considered as well.

所以這也是需要考慮的因素。

But overall, we certainly believe we have a very strong position.

但總體而言，我們確實相信我們擁有非常強勢的地位。

I also noted today that our category share in the fourth quarter was at 46%.

我今天也指出，我們第四季的品類份額為 46%。

So obviously, we have a very strong position in the marketplace.

顯然，我們在市場上佔有非常強勢的地位。

Our next question comes from the line of Tyler Van Buren with TD Cowen.

我們的下一個問題來自 TD Cowen 的 Tyler Van Buren。

Hey, guys.

嘿，大家好。

Good morning.

早安.

Thank you very much for taking the question.

非常感謝您回答這個問題。

So the dividend initiation is an exciting disclosure and earlier than some might have expected.

因此，開始派發股息是一個令人興奮的披露，而且比一些人預期的要早。

So I'm curious why you guys decided to institute the dividend now as opposed to when the Sanofi development balance was paid off by the end of next year and whether you plan to increase it from these levels over time.

所以我很好奇為什麼你們決定現在設立股息，而不是在明年年底賽諾菲發展餘額支付時設立股息，以及你們是否計劃隨著時間的推移增加股息。

Thanks, Tyler.

謝謝，泰勒。

Thanks for the question.

謝謝你的提問。

So obviously, we publicly were talking about initiating it at the end of the repayment of the Sanofi development balance.

因此很明顯，我們公開談論在賽諾菲開發餘額償還結束時啟動該計劃。

I think for a variety of reasons, we have a lot of confidence as we reiterated on the call today that, that would be paid down.

我認為，出於多種原因，我們非常有信心，正如我們在今天的電話會議上重申的那樣，這筆錢將會得到償還。

It's also obviously a differentiation in our capital allocation strategy to sort of migrate a little bit away from share buybacks, although as Len indicated in his remarks, that it will be the primary purpose of returning capital to our shareholders but allowing us a little bit more flexibility of starting the dividend.

顯然，我們的資本配置策略也有所不同，即稍微遠離股票回購，儘管正如 Len 在其評論中所指出的，這主要是為了向我們的股東返還資本，但也讓我們在開始派發股息時有更大的靈活性。

And it also opens up a larger base of shareholders.

這也開拓了更大的股東基礎。

So there are a lot of funds out there that have a dividend mandate.

因此有很多基金都有股息授權。

And this will give them the opportunity to invest in Regeneron that they wouldn't have otherwise in the past been able to do.

這將使他們有機會投資Regeneron，而這是他們過去不可能的事。

Our next question comes from the line of Cory Kasimov with Evercore.

我們的下一個問題來自 Evercore 的 Cory Kasimov。

Hey, good morning, guys.

嘿，大家早安。

I wanted to ask on the adjuvant CSCC Libtayo readout that you top lined in January.

我想問一下您在一月份列出的輔助 CSCC Libtayo 讀數。

How critical is it that the product also hits an overall survival in addition to the DFS top line?

除了 DFS 營收之外，產品的整體生存能力有多重要？

And can you kind of comment as to how you see this as the opportunity here from a commercial perspective relative to the indications you already have?

您能否評論一下，相對於您已有的跡象，從商業角度來看，您如何看待此舉帶來的機會？

Well, because these patients are relatively earlier stages of their disease, they tend to have long survival times from their initial surgeries and so forth.

因為這些病人的疾病相對較早，所以從初次手術等開始他們往往能存活很久。

So there are very few survival events.

因此存活下來的事件非常少。

That said, of course, the FDA will be looking at the data to make sure that at least numerically, things are not going in surprising or wrong directions.

當然，話雖如此，FDA 也會查看數據，以確保至少從數字上看，事情不會朝著令人驚訝或錯誤的方向發展。

But we have confidence that the package is going to look pretty attractive.

但我們相信，這個方案將會非常吸引人。

And then just adding on the commercial perspective.

然後再加上商業視角。

As I noted, we obviously have a very capable and talented oncology, Libtayo team, the US and in key international markets.

正如我所指出的，我們顯然擁有一支非常有能力和才華的腫瘤學、Libtayo 團隊、美國和主要國際市場。

But for the US, we estimate there'd be about 10,000 patients who may benefit from the adjuvant CSCC indication.

但對於美國來說，我們估計大約有 10,000 名患者可能受益於輔助 CSCC 適應症。

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

我們的下一個問題來自高盛的 Salveen Richter。

Good morning.

早安.

Thanks for taking my question.

感謝您回答我的問題。

Could you just speak to the magnitude of inventory impact on EYLEA HD that played out last quarter and also the dynamics that are happening in the marketplace with [PAV-FLU], the biosimilar?

您能否談談上個季度庫存對 EYLEA HD 的影響程度，以及生物相似藥 [PAV-FLU] 在市場上的動態？

So Salveen, as we had noted last quarter, there had been a build an EYLEA HD inventory, and that obviously impacted fourth quarter for EYLEA HD burning off that inventory.

因此，正如我們上個季度所注意到的，Salveen 已經建立了 EYLEA HD 庫存，這顯然對 EYLEA HD 第四季度產生了影響，因為庫存已經消耗殆盡。

As to the specific numbers, the range of impact in total would have been in the range of -- if we looked at the combined and EYLEA net product sales for the fourth quarter, the favorable impact was predominantly to EYLEA, and that was about $85 million, and that was the result of higher wholesale inventory levels for EYLEA partially offset by lower wholesale inventory levels for EYLEA HD.

至於具體數字，如果我們查看第四季度的綜合和 EYLEA 淨產品銷售額，總影響範圍將在以下範圍內，有利的影響主要集中在 EYLEA，約為 8500 萬美元，這是由於 EYLEA 批發庫存水平較高，但 EYLEA HD 批發庫存水平較低部分抵消了這一影響。

Do you want to comment on PAV-FLU?

您想對 PAV-FLU 發表評論嗎？

Well, it's Glenn, it's really difficult to comment on PAV-FLU.

嗯，我是格倫，對 PAV-FLU 的評論確實很難。

I will know one thing that very recently, we had some victories at the Federal Circuit Court of Appeals, which thus far is leading to the conclusion that there's only one competitor biosimilar.

我知道一件事，最近我們在聯邦巡迴上訴法院取得了一些勝利，迄今為止得出的結論是，只有一種競爭對手的生物相似藥。

If that holds, that really changes the dynamic quite a bit in terms of pricing and things like that.

如果情況屬實，那麼定價等方面的動態將會發生很大變化。

So having one competitor is quite different than having multiple competitors.

因此，擁有一個競爭對手與擁有多個競爭對手是截然不同的。

So I encourage you to look at some of the recent wins we had at the Federal Circuit on the injunctions against other players.

因此，我鼓勵你看看我們最近在聯邦巡迴法院針對其他參與者的禁令中取得的一些勝利。

In terms of what's actually going in the market, I think maybe you'll be on AMG's call this afternoon, maybe they can give you a more direct answer.

至於市場實際情況，我想也許你會在今天下午接到 AMG 的電話，也許他們可以給你更直接的答案。

Our next question comes from the line of Chris Schott with JPMorgan.

我們的下一個問題來自摩根大通的 Chris Schott。

This is Taylor Hanley on for Chris Schott.

這是泰勒漢利 (Taylor Hanley)，代替克里斯肖特 (Chris Schott)。

I just had a question on how you're thinking about operating expenses going forward.

我只是想問一下，您對未來的營運費用有何看法。

So with numerous programs advancing to late-stage development.

因此，許多專案都進入了後期開發階段。

How are you thinking about balancing investments across the pipeline?

您如何考慮平衡整個管道的投資？

And do you think that there would be the potential to partner any of these programs?

您認為這些項目有合作的潛力嗎？

Or should we think about Regeneron and keeping everything in-house going forward?

或者我們應該考慮 Regeneron 並將一切保留在公司內部？

So I think it's important to note that our primary allocation of our capital is to our research and development efforts.

因此，我認為值得注意的是，我們資本的主要分配是用於研發工作。

We're in the midst of doing a little interesting exercise that if you compare our investment to other companies and you take into account equity investments and other upfronts and milestones that essentially buying research and development, I think the data is going to show that we have an incredibly productive dollar to dollar pound for pound R&D capabilities in the industry.

我們正在做一個有趣的小練習，如果你將我們的投資與其他公司進行比較，並考慮到股權投資和其他前期付款和里程碑付款（本質上是購買研發），我認為數據將表明我們擁有業內令人難以置信的高效研發能力。

In terms of whether or not we would partner, I think we have always been -- that is a financial partner, perhaps or a strategic partner in some program.

關於我們是否會合作，我想我們一直是──也許是某個專案的財務合作夥伴，或是策略夥伴。

We've always kept an open mind to see what is the best for the program and how can we best allocate our resources.

我們始終保持開放的心態，尋求對該計劃最有利的方案以及我們如何最好地分配我們的資源。

So we don't manage the business in any fixed allocation way.

因此我們不以任何固定的分配方式來管理業務。

We don't say we're going to spend X percent.

我們並沒有說我們要花百分之多少。

We look at what's worth spending our money on.

我們看看什麼東西值得我們花錢。

We look at what the potential ways to fund our programs are and we try and make decisions that way rather than having some allocation quotas or the like.

我們會研究為我們的專案提供資金的潛在方式，並嘗試透過這種方式來做出決定，而不是採用某些分配配額或類似方法。

That flexibility, I think, has served us well, and it will continue to serve well given that we have more than 40 programs in the clinic and many, many more heading towards the clinic.

我認為，這種靈活性對我們很有幫助，考慮到我們在診所有 40 多個項目，還有更多的項目正在進入診所，這種靈活性將繼續發揮作用。

Our next question comes from the line of Christopher Raymond with Piper Sandler.

我們的下一個問題來自派珀·桑德勒 (Piper Sandler) 的克里斯托弗·雷蒙德 (Christopher Raymond)。

This is Sam on for Chris.

這是 Sam 為 Chris 表演的。

On EYLEA, we noticed you had a modest price increase, which is the first time we've seen that for EYLEA.

在EYLEA上，我們注意到你們的價格略有上漲，這是我們第一次看到EYLEA出現這種情況。

Meanwhile, we've seen Roche have more regular price increases for Mobimo since they launched.

同時，我們發現，自 Mobimo 推出以來，羅氏公司對其價格進行了更頻繁的上調。

Any comments on your pricing strategy for EYLEA going forward?

您對 EYLEA 未來的定價策略有何評論？

Is the goal to stabilize average sale price over time?

目標是隨著時間的推移穩定平均銷售價格嗎？

No comment.

沒有意見。

Okay.

好的。

I was going to say no comment.

我本來想說不予置評。

I'll add.

我補充一下。

You mentioned a price increase for EYLEA.

您提到了 EYLEA 的價格上漲。

There is a modest price increase for DHT.

DHT 的價格略有上漲。

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

我們的下一個問題來自富國銀行的 Mohit Bansal。

Great.

偉大的。

Thank you very much for taking my question.

非常感謝您回答我的問題。

Maybe, I just wanted to get a little bit more color on how you are thinking about the cadence of EYLEA HD of the year -- for the year because it seems like you're saying that you expect incremental conversion and pre-fill syringe and label expansion comes in.

也許，我只是想更多地了解您如何看待今年 EYLEA HD 的節奏——因為您似乎在說，您預計今年將會出現增量轉換和預填充注射器和標籤擴展。

Could you help us understand?

你能幫助我們理解嗎？

I mean, is it like -- is it going to be more incremental?

我的意思是，它會不會更漸進？

Or do you think that there's an infection partially due to prefiling given the market acceptability of that of that combination?

或者您是否認為，考慮到市場對該組合的接受度，存在部分由於預先歸檔而導致的感染？

Thank you.

謝謝。

Mohit, I don't have additional comment at this time.

Mohit，我目前沒有其他評論。

I wanted to give the overall balance we see obviously opportunity for EYLEA HD to continue to grow.

我想從總體上看，我們顯然看到 EYLEA HD 繼續發展的機會。

As you know, the market is probably about 10% naive patients, 90% switch patients going over to EYLEA HD and among those patients that are switching the source of business is often coming from EYLEA second forisumab and third Avastin. to the overall market dynamics, I don't have additional comments.

如你所知，市場上大概有 10% 是初治患者，90% 是轉用 EYLEA HD 的患者，而在這些轉用患者中，業務來源通常來自 EYLEA 的第二個 forisumab 和第三個 Avastin。對於整體市場動態，我沒有其他評論。

Yes.

是的。

I mean I encourage you, obviously, to look beyond the hyperfocus on EYLEA.

我的意思是，我顯然鼓勵你不要只專注於 EYLEA。

We have Dupixent launching away in -- we have pivotal data coming up with itepekimab in COPD.

我們已經推出了 Dupixent——我們掌握了 itepekimab 治療 COPD 的關鍵數據。

We have first-line melanoma, metastatic melanoma data coming up.

我們即將獲得一線黑色素瘤和轉移性黑色素瘤的數據。

Second part of this year.

今年下半年。

We've got data in myasthenia graphics coming up.

我們即將獲得重症肌無力圖表中的數據。

We're starting a trial in geographic atrophy.

我們正開始地理性萎縮的試驗。

And I could go on and on and on, and I would encourage you to work through those because our strategy is not to be solely dependent on any one thing, yet still optimize every single thing.

我可以繼續說下去，我鼓勵你們努力解決這些問題，因為我們的策略不是只依賴任何一件事，而是仍然優化每一件事。

So we will do everything we can to optimize each of our programs, HD and so forth, but we don't want to become dependent on any one thing which is why we're so excited about the pipeline.

因此，我們將竭盡全力優化我們的每一個程序、高清等等，但我們不想依賴任何一件事，這就是我們對管道如此興奮的原因。

So I would say it's the pipeline.

所以我會說這是管道。

Our next question comes from the line of Tim Anderson with Bank of America.

我們的下一個問題來自美國銀行的蒂姆·安德森。

This is Alice Nettleton on for Tim Anderson.

這是 Alice Nettleton 為 Tim Anderson 主持的節目。

Sorry, another one on EYLEA.

抱歉，EYLEA 上又有一個。

Why don't we come back to that question at the end, so we can get some non-EYLEA questions in.

我們為什麼不最後再回到這個問題上，這樣我們就可以提出一些非EYLEA 的問題。

We'll put you at the end of the queue and we'll come back to you.

我們會將您放在隊列的末尾，然後再回來找您。

Our next question comes from the line of Akash Tewari with Jefferies.

我們的下一個問題來自 Jefferies 的 Akash Tewari。

I'm not going to ask an idea question.

我不會問想法問題。

George, I'd love your take on Factor XI.

喬治，我很想聽聽你對第十一個因素的看法。

We've seen both Andexxa and some of the private map players show issues in preventing ischemic stroke events with the map also showing an inverse dose response on bleed prevention.

我們已經看到 Andexxa 和一些私人地圖玩家在預防缺血性中風事件方面都存在問題，地圖也顯示出對出血預防的逆劑量反應。

That said, Regeneron is the only company that's shown an incremental benefit in a total knee replacement study versus

儘管如此，Regeneron 是唯一一家在全膝關節置換研究中顯示出增量收益的公司，而

(inaudible).

（聽不清楚）。

So can you talk about your confidence on 5708 and some of the recent data sets in the space?

那麼您能談談您對 5708 以及該領域的一些最新數據集的信心嗎？

Yes.

是的。

Our strategy from the beginning was take advantage of our understanding from the genetics to design and select two antibodies that have very complementary with different profiles can address different patients and allow physicians and patients to choose the best antibody for their needs.

我們從一開始就採取的策略是利用我們對遺傳學的理解來設計和選擇兩種具有不同特徵且高度互補的抗體，以針對不同的患者，並允許醫生和患者根據他們的需求選擇最佳的抗體。

So our antibody that the 750 that you mentioned that hits the cata domain in side-by-side comparisons is biochemically the strongest blocker and has the strongest anticoagulant activity of anything in this class.

因此，您提到的 750 抗體在並排比較中擊中了 cata 域，從生化角度來看，它是最強的阻斷劑，並且具有此類中最強的抗凝血活性。

And that would be designed for the patients who need the most anticoagulant control.

這是為最需要抗凝血控制的患者而設計的。

And as you said, it performed very impressively in the initial proof-of-concept studies with regard to that functionality.

正如您所說，它在有關該功能的初步概念驗證研究中表現非常令人印象深刻。

The 9933, which affects the 82 domain is designed to be slightly gentler, and the genetic suggests it may have very little, if any bleeding risk but perhaps a little bit less anticoagulation activity.

影響 82 域的 9933 被設計得稍微溫和一些，基因顯示它幾乎沒有出血風險，但抗凝血活性可能稍差一些。

So that's designed to give alternatives or options for the patients and the physicians who are most concerned in that setting about bleeding risk.

因此，這旨在為最關注出血風險的患者和醫生提供替代方案或選擇。

So we think this is a very powerful optionality and flexibility to be able to offer both physicians and patients who struggle between solving the dilemma about how do I control anticoagulation without causing bleeding and all of those concerns that go with that.

因此，我們認為這是一種非常強大的可選性和靈活性，能夠為醫生和患者提供幫助，幫助他們解決如何控制抗凝血而不引起出血的難題以及隨之而來的所有問題。

And in this way, we'll have data and we'll have comparative data in multiple settings to allow the physician and the patient to hopefully choose the best approach for their situation.

這樣，我們就會有數據，並且會在多個環境下進行比較數據，以便醫生和患者能夠根據自己的情況選擇最佳的治療方法。

And we think that certainly, patients, the settings are really crying out for this sort of optionality and flexibility.

我們認為，患者確實迫切需要這種可選擇性和靈活性。

This is why so many patients in so many indications, not only in atrial fibrillation, but across the entire spectrum of diseases in which thrombi and clots are a problem are left untreated or not maximally treated.

這就是為什麼如此多的患者，不僅是心房顫動患者，而且是所有以血栓和血塊為問題的疾病患者，都未能得到治療或未得到最大限度的治療。

So we're hoping to address that huge unmet need by evaluating and getting data on these two genetically validated approaches.

因此，我們希望透過評估和獲取這兩種經過基因驗證的方法的數據來解決這一巨大的未滿足需求。

Our next question comes from the line of William Pickering with Bernstein.

我們的下一個問題來自伯恩斯坦的威廉·皮克林。

Hi, thank you for taking my question.

你好，謝謝你回答我的問題。

It's about your complement programs.

它與您的補充程序有關。

So it seems like your antibody siRNA combo has potential to deliver really leading efficacy.

因此，看起來您的抗體 siRNA 組合有可能提供真正領先的功效。

But on safety, you've seen some great AE so far -- discuss how you see these combos fitting into the MG and GA treatment landscapes.

但就安全性而言，到目前為止您已經看到了一些出色的 AE - 討論您如何看待這些組合適應 MG 和 GA 治療領域。

And for GA specifically, anything about the design of the Phase 3 trial that would kind of minimize some of those safety events that you've seen so far?

具體來說，對於 GA，第 3 階段試驗的設計是否可以盡量減少您迄今為止看到的一些安全事件？

Yes.

是的。

So first of all, the safety events are consistent with what's been seen with the class in general.

首先，安全事件與班級整體的情況一致。

Right now, we don't really have evidence to suggest that it's different than the other approaches vis-a-vis safety.

目前，我們還沒有確鑿的證據表明它與其他安全方法有何不同。

In terms of efficacy, it's an incremental benefit that is able to drive many more of the patients into the normal range.

從療效方面來看，這是一種漸進式的益處，能夠讓更多的患者恢復正常範圍。

So the current drugs can achieve in some patients as deep complement inhibition as we're seeing but they don't do it for all the patients.

因此，目前的藥物可以在某些患者身上達到我們所看到的深度補體抑制效果，但並不能對所有患者都起到這樣的作用。

We're doing it for a much higher percentage of patients.

我們為更大比例的患者提供此項服務。

So we're not really lowering complement to much lower levels, we're just driving more of the patients to the levels that are already being achieved.

因此，我們實際上並沒有將補體水平降低到更低的水平，我們只是讓更多的患者達到已經達到的水平。

This is consistent with the safety profiles being analogous to what's already been seen with the class.

這與該類別中已經看到的安全性概況類似，是一致的。

But very importantly, it's the uncontrolled patients, which are causing the problems, whether it be in PNH or perhaps some of these other complement mediate diseases who are being suboptimally treated, which we hope we now have a solution for.

但非常重要的是，正是那些不受控制的患者導致了問題，無論是 PNH 還是其他一些未得到最佳治療的補體介導疾病，我們希望現在找到了解決方案。

For those patients, roughly 30% of the population is even with the best standard of care who are left suboptimally treated.

對於這些患者，大約有 30% 的人即使接受了最好的標準護理，也未能得到最理想的治療。

That said, complement inhibition for an elderly or older AMD patient is certainly a concern with any approach.

儘管如此，對於老年或老年 AMD 患者來說，補體抑制無疑是任何治療方法所關注的問題。

And as you said, we are doing a variety of things that are somewhat standard for the class to try to choose first of all, enroll patients who are not as high risk to make sure, for example, they're vaccinated against the organisms of risk and, of course, monitoring them closely.

正如您所說，我們正在做各種各樣對於班級來說有些標準的事情，首先嘗試選擇那些風險不太高的患者，以確保他們接種了針對危險生物的疫苗，當然，還要密切監測他們。

But we have to balance that, of course, with the concerns and the safety events that have been happening with the intravitreal approaches, I mean these are designed to slow down slowly progressing vision-threatening events yet the safety events can cause catastrophic immediate vision loss in patients.

但是，當然，我們必須平衡這一點，因為人們擔心玻璃體內注射方法的安全事件，我的意思是，這些方法旨在減緩緩慢進展的視力威脅事件，但安全事件可能會導致患者立即出現災難性的視力喪失。

So that's a little bit of a dilemma.

這真是有點進退維谷。

Do you take a prevention that can make you immediately blind to slow down your eventual blindness?

您是否採取了可能讓您立即失明的預防措施，以減緩最終失明的速度？

We're hoping to offer another option for these patients that might not risk their vision.

我們希望為這些患者提供另一種可能不會損害視力的選擇。

But as you said, we'll have to balance the safety infectious types of events which, as I said, are a class-specific type of problem.

但正如你所說，我們必須平衡安全傳染類型的事件，正如我所說，這是特定類別的問題。

Thanks, George.

謝謝，喬治。

I think we have time for two more questions.

我想我們還有時間回答另外兩個問題。

Our next question comes from the line of Dave Risinger with Leerink.

我們的下一個問題來自 Leerink 的 Dave Risinger。

Yes, thanks very much.

是的，非常感謝。

So my question is on obesity.

我的問題是關於肥胖的。

George, could you please discuss the need to combine myostatin with an active in blocker to treat obesity and optimized body composition.

喬治，您能否討論一下將肌肉生長抑制素與活性阻斷劑結合起來治療肥胖症和優化身體組成的必要性。

I ask because I'm curious about whether if the Activin doesn't have the right benefit risk profile, whether you could develop a myostatin as a stand-alone or not?

我之所以問這個問題是因為我很好奇，如果 Activin 沒有正確的效益風險狀況，是否可以發展出獨立的肌肉生長抑制素？

Thanks very much.

非常感謝。

Yes, you pretty much summarized exactly our strategy based on our previous data in humans, including in sarcopenic individuals, the combination can grow more muscle.

是的，您根據我們先前在人類身上獲得的數據，準確地總結了我們的策略，包括對於肌少症患者，這種組合可以生長更多的肌肉。

However, we do have some concerns with the Activin A blockade.

然而，我們對於 Activin A 阻斷確實有一些擔憂。

The GDF8 blockade now based on both genetics and what we've seen looks to be exceedingly safe in terms of all the early data.

現在，基於遺傳學和我們所見的 GDF8 阻斷從所有早期數據來看似乎是極其安全的。

We don't have as much data with the Activin A, and so we're left with more concerns.

我們沒有太多有關 Activin A 的數據，因此我們有更多的擔憂。

So we're testing the combination, but we can fall back on just single approaches which might have a little bit less efficacy in terms of muscle preservation but might be safer.

因此，我們正在測試這種組合，但我們可以依靠單一的方法，雖然在肌肉保存方面效果可能稍差一些，但可能更安全。

So that's why we're exploring these individually, but also together.

這就是為什麼我們不僅要單獨探索這些問題，而且要一起探索這些問題。

So to understand the best benefit/risk profile I want to remind you that, for example, at Lilly, they're trying a receptor blocker that not only blocks these two growth factors but more than a dozen other related growth factors.

因此，為了了解最佳的效益/風險狀況，我想提醒您，例如，在禮來公司，他們正在嘗試一種受體阻斷劑，它不僅可以阻斷這兩種生長因子，還可以阻斷十幾種其他相關的生長因子。

So that may yield good efficacy, but the concerns there is not only you're blocking the [milestone] and the Activin A, but a dozen other factors as well. and what are the potential side effects you'll see here.

因此，這可能會產生良好的療效，但令人擔憂的是，你不僅阻礙了 [里程碑] 和 Activin A，還阻礙了其他十幾個因素。以及您將在這裡看到哪些潛在的副作用。

That's why we like our program that we can actually target the two most important factors as we've shown preclinically and clinically muscle preservation while also trying them individually.

這就是為什麼我們喜歡我們的計劃，我們實際上可以針對兩個最重要的因素，正如我們在臨床前和臨床上展示的肌肉保存，同時也單獨嘗試它們。

So that way, we'll have, once again, the most flexibility as a lot of our programs are designed to dissect and separate individual agents in various processes to understand best the benefit risk profile where you might trade efficacy for safety and vice versa.

這樣，我們將再次擁有最大的靈活性，因為我們的許多程序都是為了在不同的流程中剖析和分離單一代理而設計的，以便最好地了解效益風險狀況，您可能會用功效換取安全性，反之亦然。

Thanks, George.

謝謝，喬治。

I don't see Bank of America in the queue.

我沒有看到美國銀行在隊列。

So we'll just go to the next question in the queue is our final question.

因此我們將直接進入隊列中的下一個問題，這是我們的最後一個問題。

Our final question comes from the line of Terence Flynn with Morgan Stanley.

我們的最後一個問題來自摩根士丹利的特倫斯弗林 (Terence Flynn)。

This is Chris on for Terence.

這是克里斯，代替特倫斯。

Just a question on your Lag-3 plus PD-1 combo in non-small cell lung cancer program.

我只想問一下關於您在非小細胞肺癌專案中使用 Lag-3 加 PD-1 組合療法的問題。

What is the efficacy bar on the duration of response or PFS that you need to see for you to advance that into a pivotal program?

您需要看到什麼樣的反應持續時間或 PFS 療效標準才能將其推進到關鍵專案？

Yes.

是的。

As we've seen from the small data set with our friends at Bristol in terms of their combination, those data sets are very small, and they're hard to really make convincing conclusions on.

正如我們從布里斯託的朋友的組合小數據集中看到的那樣，這些數據集非常小，很難真正得出令人信服的結論。

That's why we are more focused on our melanoma data.

這就是我們更加關注黑色素瘤數據的原因。

If the melanoma data really deliver the sort of efficacy profile, safety and efficacy profile that we've seen in our proof-of-concept studies when we read out the Phase 3.

如果黑色素瘤數據確實提供了我們在讀出第三階段的概念驗證研究中看到的那種功效、安全性和有效性。

I think that's going to generate enormous excitement both for the potential to really help first-line melanoma patients but also to extend this combination to a variety of other cancer settings, including potentially lung cancer.

我認為這將引起極大的興奮，因為它有可能真正幫助一線黑色素瘤患者，而且可以將這種組合擴展到各種其他癌症治療，包括潛在的肺癌。

So I think that the bigger data set in the Phase 3 study is going to provide the most insight and the most potential confidence as opposed to the smaller Phase 2 and proof-of-concept studies, which obviously can generate excitement, but they're not really definitive as we've seen from our own data, but also from our friends who have other related programs going on.

因此，我認為，與規模較小的第 2 階段和概念驗證研究相比，第 3 階段研究中更大的數據集將提供最深入的見解和最潛在的信心，這顯然可以引起人們的興奮，但它們並不是真正確定的，正如我們從自己的數據中看到的那樣，也從正在進行其他相關項目的朋友的數據中看到的那樣。

So I really point to the pivotal melanoma data.

所以我確實指出了關鍵的黑色色素瘤數據。

If that really emerges as the new standard of care in melanoma, it's going to -- I think it's going to provide a lot of interest and excitement in other cancer settings as well.

如果這真的成為黑色素瘤治療的新標準，我認為它也將在其他癌症領域引起人們的極大興趣和興奮。

I see Bank of America is back in the queue.

我看到美國銀行又回到了隊列。

So we will take our final question from them as promised.

因此我們將按照承諾回答他們的最後一個問題。

Our next question comes from the line of Tim Anderson with Bank of America.

我們的下一個問題來自美國銀行的蒂姆·安德森。

This is Alice on for Tim.

這是愛麗絲為提姆表演的。

So back to my question on EYLEA.

回到我關於 EYLEA 的問題。

We talked to one big purchaser of EYLEA recently, who said that Regeneron essentially hasn't sweetened the contract terms on standard dose in an effort to compete with Amgen's product yet.

我們最近與 EYLEA 的一位大買家進行了交談，他表示，為了與安進的產品競爭，Regeneron 基本上還沒有提高標準劑量的合約條款。

So can we infer from this that you are likely to hold the ground on price and pricing concessions with the goal being that doctors will start using high dose more once the label and product enhancements come through.

因此，我們是否可以從中推斷，您可能會堅持價格和價格讓步，目標是一旦標籤和產品增強功能實現，醫生就會開始更多地使用高劑量。

Alice, thank you for your patience.

愛麗絲，謝謝你的耐心。

We don't comment on pricing strategy, but I certainly will complement our very talented market access and pricing team, but no comment.

我們不會對定價策略發表評論，但我肯定會稱讚我們非常有才華的市場准入和定價團隊，但不予置評。

With that, we will conclude the call.

至此，我們將結束本次通話。

Thank you, and thanks to everyone who dialed in for today's call.

謝謝大家，也謝謝今天接電話的所有人。

We apologize for those remaining in the Q&A queue.

對於那些仍留在問答隊列的人，我們深表歉意。

We did not have enough time to hear from you. but we're always happy to follow up.

我們沒有足夠的時間聽取您的意見。但我們始終樂意跟進。

We're available to answer any or any questions you may have.

我們隨時可以解答您可能遇到的任何問題。

Thank you once again.

再次感謝您。

Have a great day.

祝你有美好的一天。

Ladies and gentlemen, that concludes today's conference call.

女士們、先生們，今天的電話會議到此結束。

Thank you for your participation.

感謝您的參與。

You may now disconnect.

您現在可以斷開連線。