雷傑納榮製藥 (REGN) 2024 Q1 法說會逐字稿

Welcome to the Regeneron Pharmaceuticals First Quarter 2024 Earnings Conference Call. My name is Josh, and I will be your operator for today's call. (Operator Instructions). Please note that this conference call is being recorded. I will now turn the call over to Ryan Crowe, Senior Vice President, Investor Relations. You may begin.

歡迎參加再生元製藥 2024 年第一季財報電話會議。我叫喬什，我是今天電話的接線生。 （操作員說明）。請注意，本次電話會議正在錄音中。我現在將把電話轉給投資者關係高級副總裁 Ryan Crowe。你可以開始了。

Thanks, Josh. Good morning, good afternoon and good evening to everyone listening around the world. Thank you for your interest in Regeneron and welcome to our first quarter 2024 earnings conference call. An archived and transcript of this call will be available on the Regeneron Investor Relations website shortly after the call ends. 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, Senior Vice President and Chief Financial Officer. After our prepared remarks, the remaining time will be available for your questions. We anticipate today's call will last approximately 60 minutes.

謝謝，喬許。世界各地的聽眾早安、下午好、晚上好。感謝您對 Regeneron 的關注，歡迎參加我們的 2024 年第一季財報電話會議。通話結束後不久，再生元投資者關係網站將提供本次通話的存檔和文字記錄。與我一起參加今天電話會議的還有董事會聯合主席、聯合創始人、總裁兼首席執行官 Leonard Schleifer 博士； George Yancopoulos 博士，董事會聯合主席、共同創辦人、總裁兼首席科學官； Marion McCourt，商務執行副總裁；以及資深副總裁兼財務長 Chris Fenimore。在我們準備好發言後，剩下的時間將用於回答您的問題。我們預計今天的通話將持續約 60 分鐘。

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 issues, intellectual property, pending litigation and other proceedings and competition.

我想提醒您，今天電話會議的言論可能包括有關再生元的前瞻性陳述。此類聲明可能包括但不限於與再生元及其產品和業務、財務預測和指導、開發計劃和相關預期里程碑、合作、財務、監管事項、付款人覆蓋和報銷問題、智慧財產權、未決訴訟相關的聲明以及其他程序和競賽。

Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-Q for the quarter ended March 31, 2024, which was filed with the SEC this morning.

每項前瞻性陳述都存在風險和不確定性，可能導致實際結果和事件與該陳述中的預測有重大差異。有關這些風險和其他重大風險的更完整描述可以在 Regeneron 向美國證券交易委員會提交的文件中找到，其中包括今天上午向 SEC 提交的截至 2024 年 3 月 31 日的季度的 10-Q 表。

Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. 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 accessed on the Regeneron Investor Relations website. Once our call concludes, Chris and the IR team will be available to answer any further questions.

再生元不承擔任何更新任何前瞻性陳述的義務，無論是由於新資訊、未來事件或其他原因。此外，請注意，今天的電話會議將討論公認會計原則和非公認會計原則財務指標。有關我們使用非公認會計準則財務指標以及這些指標與公認會計準則的調節的信息，請參閱我們的季度業績新聞稿和公司演示文稿，這兩者都可以在再生元投資者關係網站上訪問。在我們的通話結束後，Chris 和 IR 團隊將可以回答任何進一步的問題。

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

接下來，讓我將電話轉給我們的總裁兼執行長 Leonard Schleifer 博士。萊恩？

Thanks, Ryan. Thanks to everyone joining today's call. Regeneron is off to a strong start in 2024, reflected in our solid first quarter financial results as well as the progress we have made across our pipeline in the first 4 months of the year. For my remarks today, I'd like to briefly review some of our key performance drivers and then discuss a few of our more differentiated development programs, which have the potential to drive sustainable long-term growth for the company and value for our shareholders. After my remarks, George will provide an update on our pipeline. Marion will then review our commercial performance, and Chris will discuss our financial results. First quarter 2024 revenues grew 7% after excluding last year's revenue contribution from our COVID antibodies. Growth was primarily driven by Sanofi collaboration revenues and Libtayo global net product sales, which grew by 14% and 45%, respectively.

謝謝，瑞安。感謝大家參加今天的電話會議。 Regeneron 在 2024 年迎來了一個強勁的開局，這反映在我們第一季穩健的財務業績以及我們在今年前 4 個月在管道方面取得的進展。在今天的演講中，我想簡要回顧一下我們的一些關鍵績效驅動因素，然後討論我們的一些更具差異化的發展計劃，這些計劃有潛力推動公司可持續的長期增長並為股東創造價值。在我發言後，喬治將提供有關我們管道的最新資訊。然後，馬里昂將審查我們的商業業績，克里斯將討論我們的財務表現。在排除去年我們的新冠病毒抗體的收入貢獻後，2024 年第一季的營收成長了 7%。成長主要由賽諾菲合作收入和 Libtayo 全球淨產品銷售額推動，分別成長 14% 和 45%。

Dupixent global net product sales were $3.1 billion, up 24% reflecting strong growth across all approved indications. EYLEA HD generated $200 million in its second full quarter on the U.S. market outperforming recent launches in the anti-VEGF category. Now with the permanent J-Code in place, improving payer coverage, broad prescriber familiarity and satisfaction with the EYLEA HD clinical profile and direct-to-consumer TV promotion underway. We continue to position EYLEA HD as the new standard of care for retinal diseases.

Dupixent 全球產品淨銷售額為 31 億美元，成長 24%，反映出所有核准適應症的強勁成長。 EYLEA HD 在美國市場的第二個完整季度創造了 2 億美元的收入，超過了最近推出的抗 VEGF 類別藥物。現在，隨著永久 J 代碼的到位，付款人的覆蓋範圍、廣泛的處方者對 EYLEA HD 臨床資料的熟悉度和滿意度以及正在進行的直接面向消費者的電視推廣。我們繼續將 EYLEA HD 定位為視網膜疾病護理的新標準。

Shifting to chronic obstructive pulmonary disease or COPD where Regeneron and Sanofi have 2 differentiated opportunities to transform the treatment paradigm for patients living with this debilitating disease. As announced in February, our sBLA for Dupixent for the treatment of COPD with type 2 inflammation was accepted by the FDA for priority review with a June 27 PDUFA date.

轉向慢性阻塞性肺病或慢性阻塞性肺病，再生元和賽諾菲有兩個不同的機會來改變患有這種使人衰弱的疾病的患者的治療模式。正如 2 月宣布的那樣，我們用於治療伴有 2 型發炎的 COPD 的 Dupixent 的 sBLA 已被 FDA 接受優先審查，PDUFA 日期為 6 月 27 日。

During its review of our submission, the FDA has requested additional efficacy analyses, including an information request received earlier this week regarding subpopulations from the BOREAS and NOTUS pivotal studies. Our analyses across these requested patient subgroups indicate a consistent and clinically meaningful reduction in COPD exacerbations. While the FDA has requested these analyses to be submitted by the end of May, we anticipate providing them substantially sooner. We and Sanofi are confident that these additional analyses strongly support the approval of Dupixent and eosinophilic COPD. If the FDA determines that they need additional time to review these analyses, a decision on the sBLA could be delayed for up to 3 months.

在審查我們提交的資料期間，FDA 要求進行額外的功效分析，包括本週早些時候收到的有關 BOREAS 和 NOTUS 關鍵研究亞群的資訊請求。我們對這些要求的患者亞組的分析表明，慢性阻塞性肺病 (COPD) 加重的情況一致且具有臨床意義。雖然 FDA 要求在 5 月底之前提交這些分析，但我們預計會更早提供。我們和賽諾菲相信，這些額外的分析有力地支持了 Dupixent 和嗜酸粒細胞性慢性阻塞性肺病的批准。如果 FDA 確定他們需要額外的時間來審查這些分析，則關於 sBLA 的決定可能會延遲最多 3 個月。

We and our partner, Sanofi, are preparing for launch that many pulmonologists, respiratory key opinion leaders and their patients are eagerly anticipating. If approved Dupixent will be the only biologic therapy for COPD and the first new treatment approach for this disease in more than a decade. There is a high unmet need in COPD with type 2 inflammation with approximately 300,000 eligible patients in the United States and another approximately 300,000 eligible patients in the EU and Japan, where we are also seeking regulatory approvals. Turning to itepekimab our IL-33 antibody, which is being evaluated in former smokers with COPD regardless of eosinophil phenotype. We remain on track to report results and enable potential global regulatory filings in the second half of next year.

我們和我們的合作夥伴賽諾菲正在準備推出許多肺科醫生、呼吸系統關鍵意見領袖及其患者熱切期待的產品。如果獲得批准，Dupixent 將成為 COPD 的唯一生物療法，也是十多年來針對該疾病的第一個新治療方法。患有2 型發炎的慢性阻塞性肺病(COPD) 的需求尚未得到滿足，美國大約有30 萬名符合條件的患者，歐盟和日本還有大約30 萬名符合條件的患者，我們也在這兩個國家尋求監管部門的批准。轉向 itepekimab 我們的 IL-33 抗體，該抗體正在患有慢性阻塞性肺病 (COPD) 的前吸煙者中進行評估，無論嗜酸性粒細胞表型如何。我們仍將在明年下半年報告結果並啟用潛在的全球監管備案。

Itepekimab can potentially address up to 1 million patients in the G7 countries, while China also represents a significant opportunity. We are very excited about potentially bringing these important new therapies with COPD patients while expanding our commercial respiratory franchise. In a moment, George will describe another key opportunity in our pipeline involving Dupixent in combination with our BCMAxCD3 bispecific antibody linvoseltamab which we believe has the potential to address any severe allergy and allow the millions of severe allergy sufferers to stop living in fear of an accidental exposure. Moving from linvoseltamab in severe allergy to its differentiated opportunity in multiple myeloma where it is currently under FDA and EMA review in the relapsed refractory setting. In our registration-enabling data set, while cross trial comparisons caveat supply, we believe linvoseltamab represents a best-in-class opportunity because it has the highest objective response rates and complete response rates at similar follow-ups observed across the [BCMA] bispecific class to date requires the least number of days in the hospital compared to other drugs in the category and is the only BCMA by CD3 agent currently under review or are already approved by the FDA that evaluated every 4-week dosing.

Itepikimab 有可能為七國集團國家多達 100 萬名患者提供治療，而中國也代表著一個重大機會。我們非常高興能夠為慢性阻塞性肺病患者帶來這些重要的新療法，同時擴大我們的商業呼吸特許經營權。 In a moment, George will describe another key opportunity in our pipeline involving Dupixent in combination with our BCMAxCD3 bispecific antibody linvoseltamab which we believe has the potential to address any severe allergy and allow the millions of severe allergy sufferers to stop living in fear of an accidental曝露.從用於嚴重過敏的 linvoseltamab 轉向其用於治療多發性骨髓瘤的差異化機會，目前該藥物正在接受 FDA 和 EMA 的審查，用於治療復發難治性病例。在我們的註冊資料集中，雖然交叉試驗比較警告供應，但我們相信linvoseltamab 代表了同類最佳的機會，因為它在[BCMA] 雙特異性藥物中觀察到的類似隨訪中具有最高的客觀緩解率和完全緩解率與該類別中的其他藥物相比，該類藥物迄今需要住院天數最少，並且是目前正在審查或已獲得 FDA 批准的唯一 BCMA by CD3 藥物，每 4 週給藥一次進行評估。

If approved, we believe these are all important considerations for patients, caregivers, providers and payers that could drive linvoseltamab adoption. In closing, I'm excited and energized by the differentiated opportunities in our pipeline, which now has over 35 programs in clinical development spanning many distinct therapeutic areas. Our commercial team continues to execute well and is building momentum in competitive categories, and we continue to deploy capital with the goal of driving shareholder returns over time. With that, I'll turn the call over to George.

如果獲得批准，我們相信這些都是病人、照護者、提供者和付款人的重要考慮因素，可以推動林沃司他單抗的採用。最後，我對我們管道中的差異化機會感到興奮和充滿活力，該管道目前擁有超過 35 個臨床開發項目，涵蓋許多不同的治療領域。我們的商業團隊繼續表現良好，並在競爭領域中積蓄動力，我們繼續部署資本，目標是隨著時間的推移推動股東回報。這樣，我就把電話轉給喬治。

Thanks, Len. Since Len covered the status of the Dupixent and itepekimab programs in COPD in great detail, I'd like to start with a bit more about our innovative treatment approach for severe allergies, a first-ever combination of an immunomodulatory antibody that is DUPIXENT with a bispecific antibody. Despite the remarkable benefit demonstrated by DUPIXENT across multiple diseases characterized by allergic or type 2 inflammation, DUPIXENT alone does not immediately reverse severe allergies by itself. These allergies are caused by high levels of an immunoglobulin class known as IgE made by long-lived plasma cells. This has caused some to refer the E in IgE as E for evil. Although DUPIXENT will prevent formation of new IgE plasma cells, it does not eliminate those that have already formed.

謝謝，萊恩。由於 Len 詳細介紹了 Dupixent 和 itepekimab 計畫在慢性阻塞性肺病 (COPD) 中的現狀，我想先詳細介紹一下我們針對嚴重過敏的創新治療方法，這是免疫調節抗體 DUPIXENT 與雙特異性抗體。儘管 DUPIXENT 在治療多種以過敏或 2 型發炎為特徵的疾病中表現出顯著的益處，但 DUPIXENT 本身並不能立即逆轉嚴重過敏。這些過敏是由長壽命漿細胞產生的高水平免疫球蛋白（稱為 IgE）引起的。這導致一些人將 IgE 中的 E 稱為邪惡的 E。儘管 DUPIXENT 會阻止新 IgE 漿細胞的形成，但它並不能消除那些已經形成的漿細胞。

Regeneron scientists have shown that these allergy causing IgE plasma cells can be rapidly eliminated with a short course of treatment with our bispecific antibody known as linvoseltamab. While Dupixent treatment will then prevent these cells from returning as recently highlighted in our publication and Science Translational Medicine. We have commenced our proof-of-concept clinical trial to explore the potential for this combination approach to eliminate severe food allergy. We are hoping to see initial observations from this small study later this year, which will inform next steps.

Regeneron 科學家表​​明，使用我們稱為 linvoseltamab 的雙特異性抗體進行短期治療後，可以快速消除這些引起過敏的 IgE 漿細胞。正如我們的出版物和《科學轉化醫學》最近所強調的那樣，Dupixent 治療將阻止這些細胞返回。我們已經開始概念驗證臨床試驗，以探索這種組合方法消除嚴重食物過敏的潛力。我們希望在今年稍後看到這項小型研究的初步觀察結果，這將為下一步提供資訊。

Moving on to oncology and libtayo combinations. Early clinical results of our LAG-3 antibody fianlimab in combination with libtayo suggest that these antibodies represent one of the most promising checkpoint inhibitor combinations in clinical development. Recall, fianlimab libtayo demonstrated potential for best-in-class efficacy in first-line metastatic melanoma with objective response rates of approximately 60% across 3 independent cohorts from our first-in-human study with a safety profile that is similar to that seen with anti-PD-1 monotherapy with longer-term follow-up, these initial responses continue to deepen, including patients converting into complete responses. We look forward to presenting updated results from these expansion cohorts in the second half of this year.

繼續討論腫瘤學和 libtayo 組合。我們的 LAG-3 抗體 fianlimab 與 libtayo 組合的早期臨床結果表明，這些抗體代表了臨床開發中最有前途的檢查點抑制劑組合之一。回想一下，fianlimab libtayo 在一線轉移性黑色素瘤中表現出了同類最佳療效的潛力，在我們的首次人體研究中，3 個獨立隊列的客觀緩解率約為 60%，安全性與抗PD-1單藥治療加上長期隨訪，這些最初的反應會持續加深，包括患者轉變為完全反應。我們期待在今年下半年公佈這些擴展隊列的最新結果。

Encouraged by these initial results, last year, we initiated a Phase II/III study of the combination of fianlimab and libtayo in first-line metastatic melanoma. This study is enrolling faster than expected and will now be conducted solely as a Phase III study with the final analysis to be reported during 2025. These pivotal melanoma data will inform whether fianlimab and libtayo have the potential to emerge as a new standard of care in melanoma.

受到這些初步結果的鼓舞，去年，我們啟動了 fianlimab 和 libtayo 聯合治療一線轉移性黑色素瘤的 II/III 期研究。這項研究的入組速度快於預期，目前將僅作為一項 III 期研究進行，最終分析將於 2025 年報告。瘤。

Next, to our bispecifics for hematology oncology. Regarding odronextamab, our CD20xCD3 bispecific, as announced in March, we received complete response letters from the FDA for our BLA for relapsed/refractory follicular lymphoma and relapsed/refractory diffuse large B-cell lymphoma. The only approvability issue was related to the limited enrollment of these confirmatory trials, which we intend to address as we continue to enroll patients in these studies. The EU decision on odronextamab application is expected in the second half of this year.

接下來是我們用於血液腫瘤學的雙特異性藥物。關於odronextamab，我們的CD20xCD3 雙特異性抗體，正如3 月份宣布的那樣，我們收到了FDA 就我們的複發/難治性濾泡性淋巴瘤和復發/難治性瀰漫性大B 細胞淋巴瘤BLA 發出的完整回覆函。唯一的可批准性問題與這些驗證性試驗的入組人數有限有關，我們打算在繼續招募患者參與這些研究時解決這個問題。歐盟預計將於今年下半年就 odronextamab 的應用做出決定。

Moving on to linvoseltamab. As Len noted, this bispecific continues to demonstrate a potentially best-in-class profile in late-line myeloma in terms of efficacy, safety, dosing and hospitalization burden. In an oral presentation at the recent AACR medical meeting, we presented results of an 11-month median follow-up of 117 patients. A 71% objective response rate with 46% of patients achieving a complete response or better. We are planning to present updated 14-month follow-up results at the upcoming EHA meeting in which we anticipate observing a further deepening of responses. Regarding the ongoing FDA review, we believe the confirmatory study will be sufficiently enrolled to support approval. We're also evaluating linvoseltamab in earlier stages of myeloma and in precursor conditions such as smoldering myeloma and monoclonal gammopathy of unknown significance or MGUS.

繼續使用林沃塞他單抗。正如 Len 指出的那樣，這種雙特異性藥物在晚期骨髓瘤的療效、安全性、劑量和住院負擔方面繼續表現出潛在的同類最佳特徵。在最近舉行的 AACR 醫學會議上的口頭報告中，我們介紹了對 117 名患者進行 11 個月中位數追蹤的結果。客觀緩解率為 71%，其中 46% 的患者達到完全緩解或更好。我們計劃在即將舉行的 EHA 會議上展示更新的 14 個月後續結果，我們預計在會議上觀察到進一步深化的應對措施。關於正在進行的 FDA 審查，我們相信驗證性研究將有足夠的入組人數來支持批准。我們也正在評估 linvoseltamab 在骨髓瘤早期階段和先兆條件（例如冒煙性骨髓瘤和意義不明的單克隆丙種球蛋白病或 MGUS）中的作用。

Next, to bispecifics for solid tumors. Our cost inventory bispecific antibodies are being tested in numerous studies, including as monotherapies as well as in combination with CD3 bispecifics and with libtayo. Our EGFR by CD28 bispecific in combination with libtayo, we are planning to present updated dose escalation results in an oral presentation at ASCO, most notably, in microsatellite stable colorectal cancer, a tumor historically unresponsive to immunotherapy. EGFR by CD28 in combination with libtayo demonstrated antitumor activity.

接下來是實體瘤的雙特異性藥物。我們的成本庫存雙特異性抗體正在大量研究中進行測試，包括作為單一療法以及與 CD3 雙特異性抗體和 libtayo 的組合。我們的EGFR by CD28 雙特異性藥物與libtayo 結合，我們計劃在ASCO 的口頭報告中展示更新的劑量遞增結果，尤其是微衛星穩定結直腸癌（一種歷史上對免疫治療無反應的腫瘤） 。 CD28 與 libtayo 合併使用的 EGFR 表現出抗腫瘤活性。

Regarding safety, to date, we have not observed severe immune-related adverse events with this agent at our recommended Phase II dose. Based on these data, we are enrolling dose expansion cohorts testing our EGFRxCD28 costim bispecific plus libtayo in various cancers, including non-small cell lung cancer with or without EGF receptor mutations. Microsatellite stable colorectal cancer, head and neck squamous cell carcinoma and others.

關於安全性，迄今為止，我們在建議的 II 期劑量下使用該藥物尚未觀察到嚴重的免疫相關不良事件。基於這些數據，我們正在招募劑量擴展隊列，測試我們的 EGFRxCD28 costim 雙特異性加 libtayo 在各種癌症中的作用，包括有或沒有 EGF 受體突變的非小細胞肺癌。微衛星穩定型大腸直腸癌、頭頸鱗狀細胞癌等。

On to our PSMA by CD28 costimulatory bispecific, which is already demonstrating promising activity in prostate cancer in combination with libtayo. We will soon initiate combination treatment of our PSMA by CD28 costim bispecific with our PSMA by CD3 bispecific, which based on preclinical studies, may maintain efficacy but with better tolerability.

關於我們的 CD28 共刺激雙特異性 PSMA，它已經在與 libtayo 聯合治療前列腺癌中表現出有前景的活性。我們很快就會啟動 CD28 costim 雙特異性藥物的 PSMA 與 CD3 雙特異性藥物的 PSMA 聯合治療，基於臨床前研究，可能會保持療效，但具有更好的耐受性。

We're also evaluating our MUC16xCD28 costimulatory bispecific with ubamatamab, or MUC16xCD3 bispecific as well as with libtayo, or CD3xCD28 (sic) [BCMAxCD3] costim with linvoseltamab for myeloma and our CD22xCD28 costim with odronextamab for lymphoma. Moving on to our classical hematology pipeline. Our C5 approach involves a first-in-class combination of an sRNA with an antibody for a more complete target blockade in our initial clinical data supports potential best-in-class efficacy in paroxysmal and external hemoglobinuria or PNH.

我們也正在評估我們的MUC16xCD28 與ubamatamab 共刺激雙特異性藥物，或MUC16xCD3 雙特異性藥物以及libtayo 或CD3xCD28（原文如此）[BCMAxCD3] 與linvoseltamab 的共刺激雙特異性藥物，用於治療骨髓瘤，以及我們的CD22xCD28 與odronextamab 的共刺激藥物，用於治療淋巴瘤。繼續我們的經典血液學流程。我們的 C5 方法涉及 sRNA 與抗體的一流組合，以在我們的初始臨床數據中實現更完整的標靶封鎖，支持陣發性和外部血紅蛋白尿或 PNH 的潛在最佳療效。

Results from the preliminary cohort of the PNH Phase III study will be presented at the EHA conference in June with additional results expected later this year. In addition to PNH and myasthenia gravis, which are already enrolling their respective pivotal trials, we are planning on extending the systemic combination approach to geographic atrophy in dry AMD with the first pivotal study in GA expected to get underway this year.

PNH III 期研究的初步結果將在 6 月的 EHA 會議上公佈，預計今年稍後還會有更多結果。除了已經在招募各自的關鍵試驗的 PNH 和重症肌無力之外，我們還計劃將系統性組合方法擴展到乾性 AMD 中的地理萎縮，預計今年將開始針對 GA 的第一項關鍵研究。

We are also anticipating proof-of-concept data later this year for our 2 complementary Factor XI antibodies in the setting of prevention of venous thromboembolism after knee replacement surgery. Depending on these data, 1 or both of these antibodies could remain on a rapid path to registrational studies, which could begin by late 2024 or early 2025. We -- our first-in-class antibody TMPRSS6, a genetically validated target for iron overload diseases such as beta thalassemia, is also making progress. This antibody has potential to meaningfully reduce toxic organ iron in patients whom iron chelation is inadequate or intolerable.

我們也預計今年稍後將獲得我們的 2 種互補因子 XI 抗體在預防膝關節置換手術後靜脈血栓栓塞方面的概念驗證數據。根據這些數據，這些抗體中的一種或兩種可能會繼續快速進行註冊研究，註冊研究可能會在2024 年底或2025 年初開始。標靶β地中海貧血等疾病也在取得進展。該抗體有可能有效減少鐵螯合不足或無法耐受的患者的有毒器官鐵。

Updated proof of mechanism data in healthy volunteers will be presented at the upcoming EHA conference. These results demonstrated deep sustained reductions in serum iron and robust induction of the liver hormone hepcidin, supporting the potential to release iron from organs. We are on track to start a Phase II proof-of-concept study in beta-thalassemia patients in the second half of the year.

健康志工的最新機制數據證明將在即將召開的 EHA 會議上公佈。這些結果表明血清鐵深度持續降低，肝臟激素鐵調素強烈誘導，支持從器官釋放鐵的潛力。我們預計在今年下半年針對 β 地中海貧血患者啟動一項 II 期概念驗證研究。

Moving to obesity. Our most advanced approach is designed to address potential negative consequences of widespread use of GLP GIP receptor agonist. As it has been widely reported, the profound weight loss caused by these agents, unfortunately, can also result in substantial loss of muscle, which is particularly concerning in older, obese patients. Our antibodies to myostatin-related pathways may prevent this muscle loss. Indeed, our data in obese nonhuman primates show that combining semaglutide with trevogrumab, or an antibiotic targeting myostatin with or without [pertuzumab], our antibody targeting active NA, or myostatin 2, demonstrated a comparable reduction in body weight at week 20 relative to semaglutide monotherapy, but with improved quality of weight loss resulting in more fat loss while preserving or even increasing lean mass.

轉向肥胖。我們最先進的方法旨在解決廣泛使用 GLP GIP 受體激動劑的潛在負面後果。正如廣泛報導的那樣，不幸的是，這些藥物引起的體重大幅減輕也會導致肌肉大量損失，這對於老年肥胖患者來說尤其令人擔憂。我們針對肌肉生長抑制素相關途徑的抗體可以防止這種肌肉流失。事實上，我們在肥胖非人靈長類動物中的數據表明，將索馬魯肽與特雷沃魯單抗或靶向肌生長抑制素的抗生素（有或沒有帕妥珠單抗）、我們的靶向活性NA 的抗體或肌肉生長抑制素2 相結合，在第20 週時與索馬魯肽相比，體重明顯減輕單一療法，但減肥質量提高，導致更多脂肪減少，同時保持甚至增加瘦體重。

Part A of our proof-of-concept study in healthy volunteers intended to demonstrate safety of a higher dose of trevogrumab, has completed enrollment note that over 400 subjects, including healthy volunteers in sarcopenic patients have been dosed with trevogrumab throughout its clinical development with no meaningful safety or tolerability concerns observed to date. Part B of the study, which will evaluate muscle preservation antibodies in combination with semaglutide in obese participants remains on track to start enrolling mid-year assuming a reasonable pace of enrollment, we expect to report top line results, including changes in body weight, fat mass and muscle mass in second half of 2025. I will conclude with our genetic medicines effort.

我們在健康志願者中進行的概念驗證研究的A 部分旨在證明較高劑量Trevogrumab 的安全性，已完成註冊，注意到超過400 名受試者（包括肌肉減少症患者的健康志願者）在整個臨床開發過程中接受了Trevogrumab 治療，沒有任何副作用。研究的B 部分將評估肥胖參與者的肌肉保存抗體與索馬魯肽的組合，假設註冊速度合理，我們預計將在年中開始註冊，我們預計將報告最重要的結果，包括體重、脂肪的變化2025 年下半年的質量和肌肉質量。

At the upcoming ASGCT conference, we will present updated data from our DB-OTO gene therapy program for genetic hearing loss. The first patient treated with this therapy, a 10-month old girl who is profoundly deaf at baseline. Now at 24 weeks after treatment had hearing in the normal range and the second treated patient is following a similar trajectory of improvement through earlier stages of follow-up. We are aiming to enroll several more patients this year, potentially enabling regulatory submissions by the end of next year, and we also look forward to bringing additional auditory gene therapy programs to the clinic in the coming years with the potential to address more common forms of monogenic hearing loss.

在即將舉行的 ASGCT 會議上，我們將展示針對遺傳性聽力損失的 DB-OTO 基因治療計畫的最新數據。第一個接受這種療法治療的患者是一名 10 個月大的女孩，她在基線時患有嚴重耳聾。現在，治療 24 週後，聽力已恢復正常範圍，第二位接受治療的患者在早期追蹤階段也遵循類似的改善軌跡。我們的目標是今年招募更多患者，可能在明年底之前向監管部門提交申請，我們也期待在未來幾年將更多的聽覺基因治療計畫引入臨床，有可能解決更常見的聽覺基因治療方案單基因性聽力損失。

Our collaboration with Intellia on CRISPR gene editing continues to advance. We have begun to enroll patients in the Phase III magnitude study of Intellia 2001 for a lead indication of TTR amyloidosis with cardiomyopathy. The first in vivo CRISPR program clear to enter Phase III studies in the United States. We're also on track to be the first to use CRISPR technology to insert a corrective gene in vivo for a deficiency disease. We have now achieved clearance from both the U.S. and EU authorities for our insertion program for Factor IX, and we have already enrolled initial patients into the leading portion of this program.

我們與 Intellia 在 CRISPR 基因編輯方面的合作持續推進。我們已開始招募患者參加 Intellia 2001 的 III 期研究，研究的主要適應症是 TTR 澱粉樣變性心肌病變。第一個體內 CRISPR 計畫已在美國進入 III 期研究。我們也有望成為第一個使用 CRISPR 技術在體內插入糾正基因以治療缺陷性疾病的國家。我們現已獲得美國和歐盟當局對我們的因子 IX 插入計劃的許可，並且我們已經將最初的患者納入該計劃的主要部分。

Moving on to our sRNA collaboration with Alnylam, which has not only demonstrated successful silencing of genes in the liver, but also for the first time for siRNA in the brain. Additionally, we're excited about potentially initiating later this year a potentially pivotal study for our ALN SOD treatment in ALS patients with SOD1 mutations.

接下來是我們與 Alnylam 的 sRNA 合作，該合作不僅成功地沉默了肝臟中的基因，而且還首次成功沉默了大腦中的 siRNA。此外，我們很高興可能在今年稍後啟動一項針對具有 SOD1 突變的 ALS 患者的 ALN SOD 治療的潛在關鍵研究。

With that overview, I will turn the call over to Mary.

有了這個概述，我會將電話轉給瑪麗。

Thanks, George. Our results in the first quarter demonstrate the strong performance of our commercial portfolio and future growth opportunity. We continue to strengthen and expand our leadership positions across our in-line brands, and we are preparing for potential upcoming launches. I'll start with our anti-VEGF franchise and the ongoing launch progress of EYLEA HD.

謝謝，喬治。我們第一季的業績證明了我們商業投資組合的強勁表現和未來的成長機會。我們繼續加強和擴大我們在同線品牌中的領導地位，並正在為即將推出的潛在產品做好準備。我將從我們的抗 VEGF 專營權和 EYLEA HD 的持續上市進展開始。

First quarter U.S. net sales grew 63% sequentially to $200 million as real-world experience with efficacy and safety continues to grow EYLEA HD is delivering on its promise of extending the duration between treatments, but the majority of patients achieving this goal. Retina specialists are highly satisfied with EYLEA HD as demonstrated by prescribing across a broad range of patients. To date, most EYLEA HD patients are being switched from existing medicines most notably, EYLEA and faricimab, and we are also seeing an increase in treatment-naive patients.

隨著有效性和安全性的實際經驗不斷增長，第一季美國淨銷售額環比增長63% 至2 億美元。 。視網膜專家對 EYLEA HD 非常滿意，這一點透過對廣泛患者的處方來證明。到目前為止，大多數 EYLEA HD 患者正在更換現有藥物，尤其是 EYLEA 和 Faricimab，我們也看到未經治療的患者增加。

For the quarter, EYLEA HD and EYLEA together secured 45% of the anti-VEGF category share combined U.S. net sales were $1.4 billion, which includes a reduction in wholesaler inventory of approximately $40 million. This reflects the sequential drawdown of EYLEA inventory that was partially offset by a modest increase in EYLEA HD inventory ahead of the permanent J-code on April 1. Since launch, our team has made significant progress to enhance reimbursement and market access for EYLEA HD. The permanent J-Code has increased prescribers reimbursement confidence, reflected by increased use among existing customers as well as a step-up in new customers ordering for the first time. We're very encouraged by EYLEA HD uptake despite a different payer market today compared to when EYLEA was launched more than a decade ago.

本季度，EYLEA HD 和 EYLEA 合計佔據抗 VEGF 類別份額的 45%，美國淨銷售額合計為 14 億美元，其中批發商庫存減少約 4,000 萬美元。這反映了EYLEA 庫存的連續減少，但部分被EYLEA HD 庫存在4 月1 日永久J 代碼發布之前的小幅增加所抵消。了重大進展。永久 J 代碼增強了處方者的報銷信心，這體現在現有客戶使用量的增加以及新客戶首次訂購的增加。儘管如今的支付市場與 EYLEA 十多年前推出時不同，但 EYLEA HD 的普及讓我們深受鼓舞。

For example, while more than 80% of medical benefit lives are now covered for EYLEA HD increases in utilization management or step edits are impacting all branded products. We are also highly focused on educating patients about the potential for EYLEA HD to deliver best in category vision and safety benefits with fewer injections. In mid-March, we began our direct-to-consumer TV campaign designed to raise brand awareness among treatment experienced and treatment-naive patients. Since initiating the DTC campaign, retina specialists have reported a significant increase in patients actively asking about and being prescribed EYLEA HD. In summary, the EYLEA HD launch outperformed expectations, and we are on track to establish EYLEA HD as the new standard of care for retinal disease.

例如，雖然 EYLEA HD 現在涵蓋超過 80% 的醫療福利壽命，但使用率管理或步驟編輯的增加正在影響所有品牌產品。我們也高度重視讓患者了解 EYLEA HD 以更少的注射次數提供最佳視力和安全益處的潛力。 3 月中旬，我們開始了直接面向消費者的電視活動，旨在提高有治療經驗和未接受過治療的患者的品牌知名度。自發起 DTC 活動以來，視網膜專家報告稱，主動詢問並接受 EYLEA HD 處方的患者顯著增加。總之，EYLEA HD 的推出超出了預期，我們預計將 EYLEA HD 確立為視網膜疾病護理的新標準。

Turning now to Dupixent. From our first quarter global net sales grew 25% on a constant currency basis to $3.1 billion. In the U.S., net sales grew 17% to $2.2 billion, driven by continued robust demand and the impact of customary first quarter seasonality dynamics, including annual resets of insurance plans. Dupixent is the clear leader in new-to-brand prescription share across all 5 FDA-approved indications and leads in total biologic prescriptions in 4 of its approved indications.

現在轉向 Dupixent。從第一季開始，以固定匯率計算，全球淨銷售額成長了 25%，達到 31 億美元。在美國，受持續強勁的需求以及第一季慣例季節性動態（包括年度保險計劃重置）影響的推動，淨銷售額增長 17%，達到 22 億美元。 Dupixent 在 FDA 批准的所有 5 個適應症中的新品牌處方份額中處於明顯領先地位，並且在其 4 個批准適應症中的生物處方總數中處於領先地位。

More than 850,000 patients are currently on therapy worldwide and 3 Dupixent indications have achieved blockbuster status, atopic dermatitis, asthma and nasal polyps. Across all 3 of these indications, Dupixent is competitively differentiated based on its clinical profile, depth of clinical experience and potential to be prescribed to very young patients as young as 6 months in the case of atopic dermatitis.

目前全球有超過85萬名患者正在接受治療，Dupixent的3個適應症已達到重磅炸彈狀態：異位性皮膚炎、氣喘和鼻息肉。在所有 3 個適應症中，Dupixent 因其臨床特徵、臨床經驗深度以及向 6 個月大的異位性皮膚炎患者開處方的潛力而具有競爭優勢。

We continue to see great progress with our recent launches in EoE, Dupixent's GI indication (inaudible) and dermatology. Patient initiations across both indications continue to reach all-time highs and in late January, Dupixent was approved in pediatric EOE, the brand's fourth pediatric indication. Early launch indicators are positive as Dupixent is transforming the standard of care for these children aged 1 to 11 as it has for adults and adolescents with EoE. In addition to its approved indications, there's great potential for Dupixent in an increasing list of additional type 2 diseases, including COPD. If approved, Dupixent will achieve 2 important first, the first biologic medicine for COPD and also the first new treatment in more than a decade for this devastating disease.

我們最近在 EoE、Dupixent 的 GI 適應症（聽不清楚）和皮膚病學領域的推出繼續看到巨大的進展。這兩個適應症的患者啟動繼續達到歷史最高水平，1 月底，Dupixent 在兒科 EOE 中獲得批准，這是該品牌的第四個兒科適應症。早期推出的指標是正面的，因為 Dupixent 正在改變這些 1 至 11 歲兒童的照護標準，就像它對患有 EoE 的成人和青少年一樣。除了已批准的適應症外，Dupixent 在治療越來越多的其他 2 型疾病（包括慢性阻塞性肺病）方面也具有巨大潛力。如果獲得批准，Dupixent 將實現兩個重要的第一：第一個治療慢性阻塞性肺病的生物藥物，也是十多年來針對這種毀滅性疾病的第一個新療法。

In the U.S., approximately 300,000 patients with uncontrolled COPD show evidence of type 2 inflammation. If approved, we will rapidly -- we work to rapidly establish the unique clinical benefits of Dupixent, activate physician adoption, motivate patients to seek treatment and also advance access and affordability. We are confident that COPD will drive meaningful growth for Dupixent, if approved in this indication and see an additional opportunity to address patient unmet need with itepekimab our investigational IL-33 antibody designed to help COPD patients who are former smokers. With significant runway for growth in existing and potential new indications, we are confident in Dupixent's ongoing growth trajectory.

在美國，大約 30 萬名未受控制的 COPD 患者表現出 2 型發炎的證據。如果獲得批准，我們將迅速建立 Dupixent 的獨特臨床優勢，激活醫生的採用，激勵患者尋求治療，並提高可及性和可負擔性。我們相信，如果在該適應症中獲得批准，COPD 將推動Dupixent 實現有意義的增長，並看到利用itepekimab 解決患者未滿足需求的額外機會，itepekimab 是我們的研究性IL-33 抗體，旨在幫助前吸煙者的COPD 患者。憑藉現有和潛在新適應症的顯著增長，我們對 Dupixent 的持續成長軌跡充滿信心。

And finally, to libtayo. In the first quarter, global net sales were $264 million, up 44% on a constant currency basis from the prior year, driven by our dual focus in skin and lung cancers. In non-melanoma skin cancer, libtayo continues to lead the immunotherapy category in CSCC and BCC with opportunity for continued market growth. In lung cancer, we are making steady progress in capturing category share in both monotherapy and chemotherapy combination patients. Our oncology team is also preparing for the upcoming August 22 linvoseltamab, PDUFA date recently to reinforces that linvoseltamab has the potential to be best-in-class for late-stage myeloma patients, and we look forward to its potential launch.

最後，到libtayo。在我們對皮膚癌和肺癌的雙重關注的推動下，第一季全球淨銷售額為 2.64 億美元，以固定匯率計算比上年增長 44%。在非黑色素瘤皮膚癌領域，libtayo 繼續在 CSCC 和 BCC 免疫治療類別中處於領先地位，並有機會持續市場成長。在肺癌方面，我們在單藥治療和化療聯合治療患者的類別份額方面取得了穩步進展。我們的腫瘤學團隊也在為即將到來的 8 月 22 日 linvoseltamab（PDUFA 日期）做準備，以強調 linvoseltamab 有潛力成為晚期骨髓瘤患者的同類最佳藥物，我們期待其潛在的上市。

In summary, our commercial team continues to bring important medicines to patients across an expanding range of diseases. We are focused on differentiating our medicines to increase category share and drive market growth, potential upcoming launches across our portfolio, provide the opportunity to extend the benefits of our medicines to even more patients. And with that, I'll pass the call to Chris.

總之，我們的商業團隊繼續為越來越多的疾病患者提供重要的藥物。我們專注於使我們的藥物與眾不同，以增加類別份額並推動市場成長，我們的產品組合中即將推出的潛在產品，提供了將我們的藥物的益處擴展到更多患者的機會。這樣，我就會把電話轉給克里斯。

My comments today on Regeneron's financial results and outlook will be on a non-GAAP basis unless otherwise noted. Regeneron delivered solid financial results in the first quarter of 2024. Excluding contributions from our COVID antibodies, total revenues increased 7% year-over-year to $3.1 billion, primarily driven by continued sales growth and margin expansion from Dupixent and strong global sales growth from libtayo. First quarter diluted net income per share was $9.55 due to higher Dupixent volumes, we expect the amount of these reimbursements to be comparable to 2023.

除非另有說明，我今天對再生元的財務表現和前景的評論將基於非公認會計原則。 Regeneron 在2024 年第一季實現了穩健的財務表現。來自Dupixent 的強勁全球銷售成長。由於 Dupixent 銷量增加，第一季攤薄後每股淨利潤為 9.55 美元，我們預計這些報銷金額將與 2023 年相當。

The Sanofi development balance was approximately $2.2 billion at the end of the first quarter. We anticipate this balance will be fully reimbursed by the end of 2026, which we expect will result in a significant step-up in our Sanofi collaboration profits thereafter.

截至第一季末，賽諾菲的開發餘額約為 22 億美元。我們預計這筆餘額將在 2026 年底前全額償還，我們預計這將導致此後我們與賽諾菲的合作利潤大幅增加。

Before moving to expenses, I will mention that despite lower volumes, U.S. Praluent sales in the first quarter reflected a gross to net adjustment related to a true-up of rebates due to an adverse change in payer coverage. We now expect U.S. net sales of Praluent to be modestly higher in 2024 as compared to 2023, primarily due to this adjustment. Now to our operating expenses. First quarter R&D expense grew 17% year-over-year to $1.1 billion, reflecting continued investment in our robust pipeline. SG&A grew 13% from the prior year to $544 million in the first quarter, driven by investment to support the launch of EYLEA HD, including direct-to-consumer promotion as well as higher headcount and related costs, primarily for our ongoing international commercial expansion. First quarter gross margin on net product sales was approximately 89%, which was impacted by ongoing start-up costs for our fill/finish manufacturing facility.

在談到費用之前，我要提一下，儘管銷量較低，但美國 Praluent 第一季的銷售額反映了由於付款人覆蓋範圍的不利變化而與回扣調整相關的毛淨調整。我們現在預計 2024 年 Praluent 在美國的淨銷售額將略高於 2023 年，這主要是由於這項調整。現在來談談我們的營運費用。第一季研發費用年增 17% 至 11 億美元，反映出我們對強勁產品線的持續投資。第一季的銷售、行政管理費用較上年同期成長13%，達到5.44 億美元，主要是為了支持EYLEA HD 的推出而進行的投資，包括直接面向消費者的促銷以及增加員工人數和相關成本，主要用於我們正在進行的國際商業擴張。第一季產品淨銷售額的毛利率約為 89%，這是受到我們灌裝/成品製造工廠持續啟動成本的影響。

First quarter COCM was $193 million, reflecting a decline of 22% compared to the prior year, primarily due to lower Dupixent drug substance manufacturing costs. Now to cash flow and the balance sheet. Regeneron generated $1.4 billion in free cash flow in the first quarter and ended the quarter with cash and marketable securities less debt of approximately $14.8 billion. We repurchased approximately $300 million of our shares in the first quarter and had approximately $1.2 billion available for repurchases under our February 2023 authorization at the end of the first quarter. This morning, we also announced a new $3 billion share repurchase program, which provides us with additional flexibility to continue returning capital to shareholders over time, and we remain buyers of our shares.

第一季 COCM 為 1.93 億美元，較前一年下降 22%，主要是由於 Dupixent 原料藥製造成本下降。現在來看看現金流量和資產負債表。 Regeneron 第一季產生了 14 億美元的自由現金流，季末現金和有價證券減去債務約 148 億美元。我們在第一季回購了約 3 億美元的股票，並根據 2023 年 2 月的授權，截至第一季末有約 12 億美元可用於回購。今天早上，我們還宣布了一項新的30 億美元股票回購計劃，這為我們提供了額外的靈活性，可以隨著時間的推移繼續向股東返還資本，並且我們仍然是我們股票的買家。

Finally, we have made some minor changes to our full year 2024 financial guidance. A complete summary of our latest full year guidance is available in our press release issued earlier this morning. We now expect 2024 R&D expense to be in the range of $4.4 billion to $4.6 billion. The change in R&D guidance is solely due to the inclusion of operating expenses associated with the acquisition of 2seventy bio development programs, which closed on April 1. In summary, Regeneron performed well in the first quarter and is positioned to continue to deliver strong results in 2024 and beyond. With that, I'll pass the call back to Ryan.

最後，我們對 2024 年全年財務指引進行了一些細微調整。今天早上早些時候發布的新聞稿中提供了我們最新全年指導的完整摘要。我們現在預計 2024 年的研發費用將在 44 億至 46 億美元之間。研發指導的變化完全是因為納入了與收購 2seventy 生物開發項目相關的營運費用，該項目於 4 月 1 日結束。 總之，再生元在第一季表現良好，並準備繼續在2024 年及以後。這樣，我會將電話轉回給 Ryan。

Thank you, Chris. This concludes our prepared remarks. We will now open the call for Q&A to ensure we are able to address as many questions as possible, we will answer one question from each caller before moving to the next. Josh, can we please go to the first question?

謝謝你，克里斯。我們準備好的演講到此結束。我們現在將開始問答電話，以確保我們能夠解決盡可能多的問題，我們將回答每個來電者的一個問題，然後再轉到下一個。喬希，我們可以回答第一個問題嗎？

(Operator Instructions). And our first question comes from Colin Bristow with UBS.

（操作員說明）。我們的第一個問題來自瑞銀集團的柯林布里斯托。

Congrats on the quarter. A question for George. George, there's a lot of interest, obviously, in your muscle sparing obesity program. I was wondering if you could speak to how you think this will differentiate versus competitor muscle-sparing programs and then within that, what will you be specifically paying attention to whenever Len decides to disclose the bimagrumab Phase II data?

恭喜本季。問喬治一個問題。喬治，顯然，人們對你的肌肉保護肥胖計畫很感興趣。我想知道您是否能談談您認為這將如何與競爭對手的肌肉保留計劃區分開來，然後，每當 Len 決定披露 bimagrumab II 期數據時，您將特別關注什麼？

Thanks. Great question. As when you block with other approaches like bimagrumab, you're blocking over a dozen members of the so-called BMP, GDF family and so forth. And that raises the concern because only a couple of those are actually involved in muscle preservation that you may end up doing more harm than good. What we have identified over the years is we identified 2 members of this very large family of almost 20 factors, which 2 are specifically involved in muscle preservation and we created antibodies to each of these 2 individually.

謝謝。很好的問題。當您使用 bimagrumab 等其他方法進行阻斷時，您會阻斷所謂的 BMP、GDF 家族等的十多個成員。這引起了人們的擔憂，因為其中只有少數實際上與肌肉保護有關，因此最終可能弊大於利。多年來我們已經確定的是，我們在這個由近 20 個因素組成的大家族中確定了 2 個成員，其中 2 個專門參與肌肉保存，並且我們分別針對這 2 個因子創建了抗體。

And we're testing these antibodies individually as well as together. And obviously, in this field of obesity, safety matters almost as much as efficacy here. So we believe we have the best program that is testing specifically just the specific members of this very large family that are involved in muscle preservation where they're blocking either one or both together is going to benefit the quality of the weight loss in terms of preserving muscle and maybe even causing more fat loss while creating hopefully the best possible safety profile.

我們正在單獨和一起測試這些抗體。顯然，在肥胖領域，安全性幾乎與功效同等重要。因此，我們相信我們有最好的計劃，專門測試這個非常大的家族中參與肌肉保存的特定成員，他們一起阻止其中之一或兩者將有利於減肥的質量保留肌肉，甚至可能導致更多脂肪減少，同時可望創造最佳的安全狀況。

So we think that's a big difference between our program and other programs that are blocking as I said, almost 20 different members that are involved in all sorts of things from growth factors for the bone marrow for red blood cells, controlling all sorts of things from clotting to liver function and other things and so anyway, that's the major difference in our program.

所以我們認為，我們的專案和其他專案之間有很大的區別，正如我所說，幾乎 20 個不同的成員參與了各種事情，從骨髓的生長因子到紅血球，控制從凝血對肝功能和其他方面的影響，所以無論如何，這是我們計劃的主要區別。

Our next question comes from Evan Seigerman with BMO Capital Markets.

我們的下一個問題來自 BMO 資本市場的 Evan Seigerman。

Kind of a follow-up to Colin. When you think about endpoints in muscle sparing kind of approaches in obesity, what do you think FDA would accept. Right now, they're not really accepting dexa scans, they're just looking at weight loss. Do you think that they would evolve to look at quality of weight loss as a key endpoint asset space evolves?

有點像柯林的後續。當您考慮針對肥胖症的肌肉保護方法的終點時，您認為 FDA 會接受什麼。目前，他們並沒有真正接受 dexa 掃描，他們只是專注於減肥情況。您認為隨著關鍵端點資產空間的發展，他們會逐漸專注於減肥的品質嗎？

Well, just to remind you, if you look at our paper where we did the nonhuman primate studies and so forth, is the first thing we're going to be looking for is there is the very real possibility of increased weight loss. And that might be the simplest regulatory endpoint of all. After that, if we don't see that, but we see better quality of weight loss, that could be manifested in a variety of ways, though we, of course, recognize that those would perhaps create more complicated ways of being regulated. So obviously, if you increase the fat loss while preserving muscle you should have dramatic benefits in metabolic parameters, which are often used in the field, particularly in people with diabetes and so forth as well as ultimately in terms of function by having maintenance of function as opposed to losing function and maintaining those sort of functional endpoints.

好吧，只是提醒您，如果您查看我們進行非人靈長類動物研究等的論文，我們首先要尋找的是增加體重減輕的真正可能性。這可能是最簡單的監管終點。之後，如果我們沒有看到這一點，但我們看到了更好的減肥質量，這可以透過多種方式體現出來，儘管我們當然認識到這些可能會創造更複雜的監管方式。顯然，如果你在保留肌肉的同時增加脂肪減少，你應該在代謝參數方面獲得巨大的好處，這些參數經常在該領域使用，特別是在患有糖尿病等的人中，並且最終通過維持功能在功能方面受益而不是失去功能並維持這些功能端點。

So the simplest path might be simply weight loss one could then move into metabolic parameters or muscle actual functional outcome measures. But to us, the most important thing in the Phase II study is to really just demonstrate the quality of the weight loss in terms of fat versus muscle because ultimately, if you're preserving muscle and increasing the fat loss, it has to be much better for patients, and it may avoid a lot of catastrophic long-term effects of widespread GLP-1 use and so if we see that, we think that we have a real opportunity to turn that into real widespread benefit for patients using this class of drugs.

因此，最簡單的途徑可能只是減肥，然後可以進入代謝參數或肌肉實際功能結果測量。但對我們來說，第二階段研究中最重要的事情是真正證明脂肪與肌肉方面的減肥質量，因為最終，如果你要保留肌肉並增加脂肪減少，那麼它必須多得多對患者來說更好，而且它可以避免廣泛使用GLP-1 帶來的許多災難性的長期影響，因此，如果我們看到這一點，我們認為我們有真正的機會將其轉化為對使用此類藥物的患者真正廣泛的益處藥物。

Our next question comes from Christopher Raymond with Piper Sandler.

我們的下一個問題來自克里斯托弗·雷蒙德和派珀·桑德勒。

I have a question on the EYLEA franchise. I just noticed that McKesson bought one of the largest GPOs, U.S. retina earlier this year and there's actually been -- as you guys know, a relatively long march of retina practices being rolled up by various private equity firms over the last few years. So I know this is something that's happening across a number of therapeutic specialty areas, but maybe just talk about how you see this phenomenon impacting the practice of ophthalmology in the U.S. and any changes to your go-to-market strategy? And I guess related, the inventory drawdown, we didn't see that happen last year. Was there any effect from maybe some of these changes in your customer base that sort of drove that?

我對 EYLEA 特許經營權有疑問。我剛剛注意到McKesson 今年早些時候收購了最大的GPO 之一——U.S. retina，正如你們所知，在過去的幾年裡，各種私募股權公司實際上已經進行了相對較長的視網膜業務實踐。所以我知道這是在許多治療專業領域發生的事情，但也許只是談談您如何看待這種現象對美國眼科實踐的影響以及您的上市策略有何變化？我想與庫存減少有關，去年我們沒有看到這種情況發生。您的客戶群中的某些變化是否會產生任何影響？

Sure. So let me take the inventory item first, and then I'll come back to the overall marketplace. But this was in aggregate. As I mentioned, in the quarter, we saw a reduction in wholesaler inventory broadly of about $40 million. So that reflects market-wide. But that was a combination of 2 elements. It was a sequential drawdown of EYLEA inventory that was partially offset by a modest increase in EYLEA HD inventory ahead of the permanent J-Code on April 1. And then I would share on the overall market in all the categories where we participate, we're always very conscious of the segmentation of the market, targeting the market, what's occurring in terms of customer base and certainly, our strategies and our approach to the marketplace is reflective of that. And the range of customers we have, as you point out, in retina and how that market has evolved over time. And I think our commercialization approach has been very effective in addressing that market evolution.

當然。所以讓我先看看庫存項目，然後我再回到整個市場。但這是總體而言。正如我所提到的，在本季度，我們看到批發商庫存大致減少了約 4000 萬美元。這反映了整個市場。但這是兩個元素的組合。這是 EYLEA 庫存的連續減少，部分被 EYLEA HD 庫存在 4 月 1 日永久 J 代碼之前的小幅增加所抵消。 、市場定位、客戶群的變化，當然，我們的策略和市場方法也反映了這一點。正如您所指出的，我們在視網膜領域擁有的客戶範圍以及該市場如何隨著時間的推移而演變。我認為我們的商業化方法在應對市場演變方面非常有效。

Our next question comes from Salveen Richter with Goldman Sachs.

我們的下一個問題來自高盛的 Salveen Richter。

With regard to the COPD program here, it doesn't seem like this is an approvability question. So could you just speak to whether restrictions to specific subpopulations could be possible, albeit noting that you had a subpopulation analysis that was consistent with the broader data.

關於這裡的慢性阻塞性肺病項目，這似乎不是一個可否批准的問題。那麼，您能否談談是否可以對特定亞群進行限制，儘管您指出您的亞群分析與更廣泛的數據一致。

Yes, Salveen, thanks for the question. You're right. From our perspective, we think the data broadly supports the entire BLA and as well as all these analyses, the approval of the drug in eosinophilic COPD. As you might imagine, the FDA went anticipating or looking at a new class of biologics is very interested in checking it up and down and down and up and making sure that there's no subpopulation of the study that might be driving the data. So they might -- if one saw that, one might think about labeling it differently, but none of that has occurred. We've looked at all these analyses. We're going to submit them a way ahead of the schedule that they've asked for, and all of the analyses show a consistent and clinically meaningful reduction in the COPD exacerbations across all of these subgroups that have been asked for.

是的，薩爾文，謝謝你的提問。你說得對。從我們的角度來看，我們認為這些數據廣泛支持整個 BLA 以及所有這些分析，支持該藥物治療嗜酸性粒細胞性慢性阻塞性肺病。正如你可能想像的那樣，FDA 正在預期或研究一種新的生物製劑，並且非常有興趣對其進行上下檢查，並確保該研究中沒有任何亞群可能會驅動數據。所以他們可能——如果有人看到這一點，人們可能會考慮以不同的方式給它貼上標籤，但這些都沒有發生。我們已經看過所有這些分析。我們將比他們要求的時間表提前提交它們，所有分析都顯示，所有這些亞組所要求的 COPD 惡化均出現了一致且具有臨床意義的減少。

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

我們的下一個問題來自泰勒·範布倫 (Tyler Van Buren) 和 TD Cowen。

For this initial severe food allergy study and the results by year-end, could you elaborate on exactly what will be reported and what you would hope to see to have early clinical proof of concept and how long do you anticipate that these patients would stay on Dupixent in order to maintain low or no IgE levels?

對於這項最初的嚴重食物過敏研究和年底的結果，您能否詳細說明將報告什麼內容以及您希望看到什麼以獲得早期臨床概念證明以及您預計這些患者會繼續治療多久Dupixent 是為了維持低IgE水平或無IgE 水平？

These are great questions. We hope from the first few patients if the results are as dramatic as they are in the preclinical studies that we'll be seeing meaningful indicators that we are really reversing severe food allergy. Of course, the first thing and the most important biomarker, as I said, is this evil immunoglobulin IgE, which you can both measure, but they are also routinely tested using these skin prick tests, which are how people are actually evaluated for allergies.

這些都是很好的問題。我們希望，如果結果像臨床前研究那樣引人注目，我們將從最初的幾位患者身上看到有意義的指標，表明我們確實正在逆轉嚴重的食物過敏。當然，正如我所說，第一件事也是最重要的生物標記是這種邪惡的免疫球蛋白IgE，您都可以測量它，但它們也經常使用這些皮膚點刺測試進行測試，這就是人們實際上評估過敏的方式。

So we expect, first of all, to be seeing that happening in the study in obvious ways. And then we can follow that up, and it is allowed in the study if we see dramatic responses in these markers of the actual allergy-causing immunoglobulin to then go on and do actual food challenges and so forth in the patients. So it all depends on how obvious the reductions in this [IgE are] and if they are really dramatic, we can go on and do additional allergen-challenged tests. But we hope if the humans behave like the nonhuman primate that we might be seeing something dramatic in the initial patients.

因此，我們首先期望在研究中以明顯的方式看到這種情況的發生。然後我們可以跟進，如果我們看到這些實際引起過敏的免疫球蛋白標記物發生顯著反應，那麼研究中就允許繼續對患者進行實際的食物挑戰等。因此，這一切都取決於 [IgE] 的減少有多明顯，如果確實顯著減少，我們可以繼續進行額外的過敏原測試。但我們希望，如果人類表現得像非人類靈長類動物，我們可能會在最初的患者身上看到一些戲劇性的東西。

George, can you comment? I think they also want to know how long you have to stay on IgG...

喬治，你能評論一下嗎？我想他們也想知道你必須堅持使用 IgG 多久...

Yes. The interesting thing is the animal study suggests that the antibodies against the allergens come back as IgG, G for good antibodies. The whole point of -- if you guys are familiar with so-called immunotherapy or desensitization therapy, all of those therapies, what they're trying to do is induce production of IgG to overwhelm the IgE. That's a much harder thing to do because they're not really getting rid of the Ig. They just have to overwhelm with a lot more IgG. In the animal studies, it suggests that we get rid of the Ig and we replace it with IgG. We don't know, obviously, in the humans, it may be possible that short-term treatment, relatively short-term treatment, may allow patients who have replaced their IgE with IgG, and they will have long-term protection.

是的。有趣的是，動物研究表明，針對過敏原的抗體以 IgG 形式回歸，G 代表良好的抗體。如果你們熟悉所謂的免疫療法或脫敏療法，那麼所有這些療法的重點就是誘導 IgG 的產生來壓倒 IgE。這是一件更難的事情，因為他們並沒有真正消除 Ig。他們只需要攝取更多的 IgG 就可以了。在動物研究中，建議我們去除 Ig，並用 IgG 代替。顯然，我們不知道，在人類中，短期治療，相對短期的治療，可能會讓患者用 IgG 取代 IgE，他們將獲得長期保護。

On the other hand, we may see that to prevent these patients from making Ig and more IgGs in the future that they may have to stay on the Dupixent for substantial long periods of time. The good news about that as we all know and as was highlighted in Marion's comments, Dupixent compared to most other immunomodulatory agents, it's not immunosuppressive. It actually is corrective for the immune system. And as indicated by its labeling to very, very young patients, it's a very, very relatively safe immunomodulator and biologic. And since most people who have severe allergies also have a lot of other concomitant atopic diseases.

另一方面，我們可能會發現，為了防止這些患者將來產生 Ig 和更多 IgG，他們可能必須長期服用 Dupixent。好消息是，眾所周知，正如 Marion 評論中所強調的那樣，Dupixent 與大多數其他免疫調節劑相比，它不具有免疫抑製作用。它實際上可以糾正免疫系統。正如它對非常非常年輕的患者的標籤所示，它是一種非常非常相對安全的免疫調節劑和生物製劑。而且由於大多數患有嚴重過敏的人還患有許多其他伴隨的特異性疾病。

It may be that it is best for these patients to keep their abnormal atopy or abnormal type 2 inflammation under control. So short answer is it's -- there's a possibility it could be relatively short term, but there's also a possibility at least for some or the majority of patients, it could be relatively long term. But the good news is that they may actually have a long-term benefit for the patients because these patients are almost by definition, what you call atopic patients who might need control of their type 2 excess inflammation.

對於這些患者來說，最好控制其異常特異性或異常 2 型發炎。所以簡短的答案是——有可能是相對短期的，但至少對一些或大多數患者來說，也有可能是相對長期的。但好消息是，它們實際上可能會給患者帶來長期益處，因為根據定義，這些患者幾乎都是所謂的特異性患者，他們可能需要控制 2 型過度發炎。

Our next question comes from Terence Flynn with Morgan Stanley.

我們的下一個問題來自摩根士丹利的特倫斯·弗林。

Just had one on your LAG-3 program. Obviously, you guys are aware that Bristol discussed seeing a signal in a subset of lung cancer that benefits from a combination of PD-1 and LAG-3. So I would just love your latest thoughts on how to think about that in the context of both your program and then what you're hoping to see with this Phase II data later this year?

您的 LAG-3 計劃中剛剛有一個。顯然，你們都知道 Bristol 討論過在肺癌子集中看到一個信號，該信號受益於 PD-1 和 LAG-3 的組合。所以我很想知道您關於如何在您的計劃的背景下思考這個問題的最新想法，以及您希望在今年晚些時候透過第二階段數據看到什麼？

Right. That's a great question. Obviously, the thing that gets us excited about our program compare to the field is that we've seen levels of activity that haven't been seen in the other LAG-3 programs, particularly in melanoma. If that's true in melanoma, there would be hope that this would be seen broadly in other settings and indications. We are certainly excited to see the follow-up details on the BMS story with potential activity in a specific subpopulation that will certainly help point us in our own studies to see what we're seeing within that subpopulation that they are talking about as well as more broadly. But of course, the hope, as I said, is if it is indeed more active in one setting such as melanoma, the hope is it will be broadly more active across other cancer settings as well. So we are excited to see follow-up on their data. We're excited to see follow-up on our data, both in melanoma and in our lung studies.

正確的。這是一個很好的問題。顯然，與該領域相比，我們的計畫讓我們感到興奮的是，我們看到了其他 LAG-3 計畫中未曾見過的活性水平，特別是在黑色素瘤中。如果黑色素瘤確實如此，那麼就有希望在其他環境和適應症中廣泛看到這一點。我們當然很高興看到 BMS 故事的後續細節以及特定亞群中的潛在活動，這肯定會幫助我們在自己的研究中了解我們在他們正在談論的亞群中看到的情況以及更廣泛地。但當然，正如我所說，如果它確實在黑色素瘤等一種情況下更加活躍，那麼我們希望它在其他癌症情況下也會更加活躍。因此，我們很高興看到他們的數據的後續行動。我們很高興看到黑色素瘤和肺部研究數據的後續進展。

Next question comes from William Pickering with Bernstein.

下一個問題來自威廉·皮克林和伯恩斯坦。

I had a follow-up on the food allergy program. Could you comment on the dose of linvoseltamab that you'll be testing as compared to the myeloma setting? How -- what gives you confidence in the safety profile and if a patient misses a Dupixent dose, would they then need to start over again with linvo?

我對食物過敏計劃進行了跟進。您能否評論一下您將要測試的與骨髓瘤環境相比的林沃塞他單抗劑量？是什麼讓您對安全性充滿信心？

Yes, these are all great questions. What we've already actually shown based on a variety of studies that we've done is that normal nonmalignant noncancerous plasma cells, the cells that are the immunoglobulin factory cells are the normal versions of the cells are much more susceptible to the bispecific than our malignant myeloma cells. So in discussions and communications with the FDA, we're actually starting at much lower doses than the doses that are used in the myeloma programs, though there is an intrapatient dose escalation process. So we're literally watching -- we're starting with low doses and we're going up in the doses until we actually hopefully see elimination of the IgE. That said, in terms of the safety, I'd just remind you that the much higher myeloma doses, we came up as Len briefly summarized in this program.

是的，這些都是很好的問題。根據我們所做的各種研究，我們實際上已經表明，正常的非惡性非癌性漿細胞，即免疫球蛋白工廠細胞，是細胞的正常版本，比我們的細胞更容易受到雙特異性抗體的影響。因此，在與 FDA 的討論和溝通中，我們實際上從比骨髓瘤計畫中使用的劑量低得多的劑量開始，儘管存在患者內劑量遞增過程。所以我們實際上是在觀察——我們從低劑量開始，然後逐漸增加劑量，直到我們真正希望看到 IgE 被消除。也就是說，就安全性而言，我只是提醒您，骨髓瘤劑量要高得多，正如 Len 在本計劃中簡要總結的那樣。

We believe that we have a differentiated program in terms of not only efficacy and hospitalization burden and so forth, but also in safety. We have less than 1% Grade 3 events at those high doses in the much sicker myeloma patients. So we hope and we expect that with lower doses in a much healthier population, that this will be a hopefully pretty well tolerated approach. And a much shorter, yes. We think that ultimately, we make it by with a single short course or a very short course of treatment. In terms of whether if somebody takes a holiday, whether one has to then start all over again with the elimination of the IgE cells, we think probably not because it takes a long time to get to those levels of IgE.

我們相信，我們不僅在療效和住院負擔等方面，而且在安全性方面都有差異化的方案。在病情嚴重的骨髓瘤患者中，高劑量下發生 3 級事件的比例不到 1%。因此，我們希望並且預計，在更健康的人群中，劑量更低，這將是一種耐受性良好的方法。而且更短，是的。我們認為最終我們可以透過單一的短期療程或非常短的療程來實現這一目標。至於是否有人去度假，是否必須從頭開始消除 IgE 細胞，我們認為可能不會，因為需要很長時間才能達到 IgE 的水平。

So just delaying for a short period of time, we may not bounce back to those levels. As I said, you may have converted all of those cells to IgG or good sales by that point anyway. But of course, we have to be doing the studies, and we have to be looking at these patients in the clinic to really understand. When I -- I should mention that the Grade 3 events that I was talking about are reflected by cytokine release syndrome. A lot of that is also thought to be -- due to the load of the cancer cells. And obviously, these normal patients have much less of a load here. So it's just another reason to expect, hopefully, better safety. We're going to be going with lower doses, more gentle treatment, and they have much less load in there, so you would expect much less reason to be seeing things like cytokine release syndrome.

因此，僅僅推遲一小段時間，我們可能不會反彈到這些水平。正如我所說，到那時您可能已經將所有這些細胞轉化為 IgG 或取得了良好的銷售表現。但當然，我們必須進行研究，我們必須在診所觀察這些患者才能真正理解。當我——我應該提到，我所說的 3 級事件是由細胞激素釋放症候群反映出來的。其中很大一部分也被認為是由於癌細胞的負荷所造成的。顯然，這些正常患者的負擔要小得多。因此，這只是期望更好的安全性的另一個原因。我們將採用更低的劑量、更溫和的治療，而且它們的負荷要小得多，所以你會期望更少的理由看到細胞激素釋放綜合症之類的事情。

Our next question comes from Carter Gould with Barclays.

我們的下一個問題來自巴克萊銀行的卡特·古爾德。

I wanted to ask another follow-up sort of bispecifics in autoimmune, but I want to go down a little bit of a different path acknowledging the BCMA in Dupi effort. But we've seen sort of CAR-T efforts and ADC approaches sort of come to the rise in lupus and other autoimmune disorders and naturally, people have then started talking about T cell engagers. This seems like a natural place where Regeneron could leverage its bispecific capabilities, expertise. Are there efforts underway internally on this front? Has Regeneron looked at ways to leverage in that expertise?

我想問自體免疫方面的另一種後續雙特異性，但我想走一點不同的道路，承認 BCMA 在 Dupi 的努力。但我們已經看到 CAR-T 的努力和 ADC 方法在狼瘡和其他自體免疫疾病方面增加，自然地，人們開始談論 T 細胞接合者。這似乎是再生元可以利用其雙特異性能力和專業知識的自然場所。內部是否正在這方面努力？再生元是否考慮過利用這些專業知識的方法？

That's a phenomenal question. And first of all, let me remind you that with our long-term collaboration and recent acquisition of 2seventy. 2seventy had exactly the sort of CAR-T programs that you're referring to in lupus and other autoimmune settings, which we are now obviously pursuing together with them but that is one of the reasons why we were excited about turning the collaboration into a situation where we brought all the expertise and the scientists and leadership from 2seventy in-house because we're doing exactly what you suggested. We're hoping to actually literally look in side-by-side studies, how CAR-T approaches in these settings of autoimmune, severe autoimmune disease like lupus and so forth, compare directly head-to-head to our bispecifics. And as you are sort of suggesting, you would think that there would be really little reason to think that the CAR-T solutions would be preferable in this setting, both in terms of off-the-shelf mess and the ability to eliminate the normal cells.

這是一個了不起的問題。首先，讓我提醒您，我們的長期合作以及最近對 2seventy 的收購。 2seventy 的CAR-T 計畫正是您在狼瘡和其他自體免疫疾病中提到的那種，我們現在顯然正在與他們一起追求，但這也是我們對將合作轉變為一種情況感到興奮的原因之一我們帶來了 2seventy 內部的所有專業知識、科學家和領導力，因為我們正在按照您的建議行事。我們希望能夠真正進行平行研究，了解 CAR-T 如何治療自體免疫性、嚴重自體免疫疾病（如狼瘡等），並與我們的雙特異性藥物進行直接正面比較。正如您所暗示的那樣，您可能會認為，無論是在現成的混亂還是消除正常現象的能力方面，沒有什麼理由認為 CAR-T 解決方案在這種情況下會更可取。

As I said, it's usually a lot easier to get rid of normal cells than it is malignant cells. So whatever advantages you might have in certain settings of CAR-Ts you would think in the normal disease setting or at least normal cells in autoimmune disease settings that bispecifics might be just as good, much more convenient and much safer. So together with now our internal Regeneron cell medicines group that has involved a lot of the expertise and leadership of 2seventy, we're exploring that exact question.

正如我所說，清除正常細胞通常比清除惡性細胞容易得多。因此，無論您在某些CAR-T 環境中可能擁有什麼優勢，您都會認為在正常疾病環境中或至少在自體免疫疾病環境中的正常細胞中，雙特異性抗體可能同樣好、更方便、更安全。因此，我們現在與擁有 2seventy 的大量專業知識和領導力的內部再生元細胞藥物小組一起，正在探索這個確切的問題。

I should also say that as clearly been announced by the company and is available in our public disclosures, we have already initiated separately a variety of studies looking at our bispecifics to decrease autoantibodies and autoimmune diseases in other settings as well. So we were already looking at this, but now we're looking at these in direct comparison to our CAR-T approaches with our now internal Regeneron cell medicines efforts.

我還應該說，正如公司明確宣布的那樣，並且在我們的公開披露中可以找到，我們已經分別啟動了各種研究，著眼於我們的雙特異性藥物，以減少其他環境中的自身抗體和自身免疫性疾病。所以我們已經在研究這個，但現在我們正在將這些與我們的 CAR-T 方法和我們現在內部的再生元細胞藥物工作進行直接比較。

Next question comes from Brian Abrahams with RBC Capital Markets.

下一個問題來自加拿大皇家銀行資本市場部的布萊恩‧亞伯拉罕斯 (Brian Abrahams)。

Congrats on all the progress. I know docs are really excited for Dupi and COPD, but it is a new space for biologics. So I'm curious, the amount of education you think is going to be required and how this might affect the initial uptake trajectory. And then how you're thinking the introduction of other biologics, which have also been showing promise might impact the overall long-term market here in Dupi's positioning?

祝賀所有的進展。我知道醫生們對 Dupi 和 COPD 感到非常興奮，但這是生物製劑的一個新領域。所以我很好奇，您認為需要多少教育以及這可能如何影響最初的接受軌跡。那麼您如何看待其他生物製劑的引入，這些生物製劑也已顯示出前景，可能會影響 Dupi 定位的整體長期市場？

So certainly, we look forward to the potential launch of Dupixent in COPD. There's such unmet need and such opportunity to help those patients with an eosinophilic COPD. Our team, as you know, is very experienced with launches in Dupixent. So work is very much underway at Regeneron and also with, obviously, under our collaboration with Sanofi to make sure that we apply the best practices and launch of new indications.

因此，我們當然期待 Dupixent 可能在慢性阻塞性肺病 (COPD) 中上市。有如此未滿足的需求和機會來幫助嗜酸粒細胞性慢性阻塞性肺病患者。如您所知，我們的團隊在 Dupixent 的發布方面擁有豐富的經驗。因此，再生元的工作正在進行中，顯然，我們與賽諾菲的合作也正在進行中，以確保我們應用最佳實踐並推出新的適應症。

I will share that many of these physicians have already experienced use of Dupixent with tremendous results. We've made great progress, as you know, in asthma leading in new scripts and certainly making tremendous overall performance strides. But we will be very thoughtful on how best to reach physicians, how to make sure that we're aligned with reimbursement and affordability for patients, educating in the way we've come to understand is best for Dupixent in the various markets and indications that we've entered. So we look forward to this opportunity.

我將分享的是，這些醫生中的許多人已經體驗過 Dupixent 的使用並取得了巨大的結果。如您所知，我們在氣喘領域取得了巨大進展，推出了新的腳本，當然也取得了巨大的整體效能進步。但我們將非常深思熟慮地考慮如何最好地聯繫醫生，如何確保我們與患者的報銷和負擔能力保持一致，以我們所了解的最適合 Dupixent 在各個市場和跡象的方式進行教育我們已經進入了。所以我們期待這個機會。

Our next question comes from Mohit Bansal with Wells Fargo.

我們的下一個問題來自富國銀行的 Mohit Bansal。

I have a question on itepekimab so in our conversation and literature search, it suggests that there may be a potential for disease modification with some kind of remodeling at this mechanism. Just wanted to see if you think that is possible? And what markets would you be looking forward to in the Phase III trial beyond exacerbation when the data come.

我對 itepekimab 有一個疑問，因此在我們的對話和文獻檢索中，它表明透過對該機制進行某種重塑可能有潛力改善疾病。只是想看看您認為這是否可能？當數據到來時，您對第三階段試驗除了惡化之外還期待哪些市場。

Well, there's always the possibility of disease modification. We actually believe, for example, Dupixent in asthma may be doing exactly that sort of benefit. One of the best ways of actually looking at that is looking at overall loss of lung function over time because, as you know, in these lung diseases as Marion said, in both asthma and COPD, these are diseases of the lungs followed largely by pulmonologists, the same sort of doctors and it is well known that in both of these diseases over time, patients start permanently losing lung capacity and lung function. We are and have been and have early data suggesting that Dupixent may prefer that in asthma, and we'll certainly be looking at those sorts of things for not only Dupixent but itepekimab in the COPD patients in terms of modifying disease and long-term preservation and prevention of this otherwise unstoppable lung function loss.

嗯，疾病改變的可能性總是存在的。例如，我們實際上相信，Dupixent 治療氣喘可能正是具有這種功效。實際觀察這個問題的最佳方法之一是觀察隨著時間的推移肺功能的整體喪失，因為正如馬里恩所說，在哮喘和慢性阻塞性肺病等肺部疾病中，這些都是肺病專家主要關注的肺部疾病，同樣類型的醫生，眾所周知，隨著時間的推移，這兩種疾病的患者開始永久喪失肺活量和肺功能。我們現在和過去都有早期數據表明 Dupixent 可能更喜歡治療氣喘，而且我們肯定會在慢性阻塞性肺病患者中研究 Dupixent 和 itepekimab 在改變疾病和長期保存方面的作用以及預防這種無法阻止的肺功能喪失。

And our last question comes from Chris Schott with JPMorgan.

我們的最後一個問題來自摩根大通的克里斯·肖特。

This is Taylor on for Chris Schott. So we were wondering, would you elaborate a little bit more about how you're thinking about the linvoseltamab launch as we approach the August PDUFA and then thinking about the field more broadly in myeloma, how are you thinking about MRD negativity as a surrogate and thoughts on how you might be able to move into earlier lines in myeloma faster?

這是泰勒替克里斯·肖特發言。因此，我們想知道，當我們接近 8 月 PDUFA 時，您能否詳細說明您如何看待 linvoseltamab 的推出，然後更廣泛地考慮骨髓瘤領域，您如何看待 MRD 陰性作為替代品以及您是否想過如何能夠更快進入骨髓瘤的早期階段？

Mary can take the question on the launch and everything. I mean, obviously, the MRD negativity as endorsed by that panel gives an opportunity to get these kinds of drugs to patients earlier in a variety of settings. So we are looking forward to applying that approach in our future studies as we move towards earlier in different lines of therapy. Marion on the launch?

瑪麗可以回答有關發射和一切的問題。我的意思是，顯然，該小組所認可的 MRD 陰性為在各種情況下儘早為患者提供此類藥物提供了機會。因此，隨著我們在不同治療領域的早期發展，我們期待在未來的研究中應用這種方法。馬里昂在發射？

Sure. So we're certainly preparing for the potential launch with the August 22 PDUFA date. And we're really excited because as I've mentioned before, the recent data reinforces linvoseltamab as potentially a best-in-class product for late-stage myeloma patients. So it's a wonderful opportunity to extend our oncology franchise in the new disease area.

當然。因此，我們肯定正在為 8 月 22 日 PDUFA 日期的潛在發布做準備。我們真的很興奮，因為正如我之前提到的，最近的數據強化了 linvoseltamab 作為晚期骨髓瘤患者的潛在同類最佳產品。因此，這是擴展我們在新疾病領域的腫瘤學專營權的絕佳機會。

All right. Thanks, Len and Marion, and thanks to everyone who dialed in for your interest in Regeneron. We apologize to those remaining in the queue that we did not have a chance to hear from. As always, the IR team here at Regeneron is available to answer any remaining questions that you may have. Thank you once again, and have a great day.

好的。謝謝 Len 和 Marion，也謝謝所有撥通電話表示對再生元有興趣的人。我們向那些留在隊列中但沒有機會收到訊息的人表示歉意。像往常一樣，Regeneron 的 IR 團隊可以回答您可能遇到的任何剩餘問題。再次感謝您，祝您有美好的一天。

Thank you. This concludes the conference. Thank you for your participation. You may now disconnect.

謝謝。會議到此結束。感謝您的參與。您現在可以斷開連線。