雷傑納榮製藥 (REGN) 2025 Q1 法說會逐字稿

Welcome to the Regeneron Pharmaceuticals first-quarter 2025 earnings conference call.

歡迎參加再生元製藥 2025 年第一季財報電話會議。

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

我叫喬希，今天我將擔任您的電話接線生。

(Operator Instructions)

（操作員指示）

Please note that this conference call is being recorded.

請注意，本次電話會議正在錄音。

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

現在我將電話轉給投資人關係資深副總裁 Ryan Crowe。你可以開始了。

Thank you, Josh.

謝謝你，喬希。

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

向全世界聽眾致上最誠摯的問候：早安、下午好、晚上好。

Thank you for your interest in Regeneron and welcome to our first quarter 2025 earnings conference call.

感謝您對 Regeneron 的關注，歡迎參加我們的 2025 年第一季財報電話會議。

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

此次電話會議的存檔和記錄將在會議結束後不久在 Regeneron 的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席主席、聯合創始人、總裁兼首席執行官 Leonard Schleifer 博士；喬治·揚科普洛斯博士 (George Yancopoulos)，董事會聯席主席、聯合創始人、總裁兼首席科學官；商務執行副總裁 Marion McCourt；以及執行副總裁兼首席財務官克里斯·費尼莫爾 (Chris Fenimore)。

After our prepared remarks, the remaining time will be available for Q&A.

在我們準備好發言之後，剩餘的時間將用於問答。

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 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. 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, 2025, which was filed with the SEC this morning. Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events, or otherwise. In addition, please note that GAAP and non-GAAP financial measures will be discussed on today's call. Information regarding our use of non-GAAP financial measures and a reconciliation of those measures to GAAP is available in our quarterly results press release and our corporate presentation, both of which can be found on the Regeneron Investor Relations website. Once our call concludes, the IR team will be available to answer any further questions.

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。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、指導、開發計劃和相關預期里程碑、合作、財務、監管事項、付款人承保和報銷、知識產權、未決訴訟和其他程序以及競爭相關的聲明。每個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，包括今天上午向美國證券交易委員會提交的截至 2025 年 3 月 31 日的季度 10-Q 表。無論是因為新資訊、未來事件或其他原因，Regeneron 均不承擔更新任何前瞻性聲明的義務。此外，請注意，今天的電話會議將討論 GAAP 和非 GAAP 財務指標。有關我們使用非 GAAP 財務指標以及這些指標與 GAAP 的調節的信息，請參閱我們的季度業績新聞稿和公司介紹，這兩份文件均可在 Regeneron 投資者關係網站上找到。通話結束後，IR 團隊將隨時解答您的任何進一步的問題。

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

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

Thanks, Ryan and thanks to everyone joining today's call.

謝謝，瑞安，也感謝今天參加電話會議的所有人。

For my remarks, I will review some of our key performance drivers, then briefly discuss some pipeline advances we've made this year. I will then hand the call over to George, who will provide additional insights on our pipeline.

在我的演講中，我將回顧我們的一些關鍵績效驅動因素，然後簡要討論我們今年取得的一些管道進展。然後我會把電話交給喬治，他將對我們的管道提供更多見解。

From there, Marion will review our first quarter 2025 commercial performance, and finally, Chris will detail our financial results and provide an update on our 2025 financial outlook.

首先，馬里恩將回顧我們 2025 年第一季的商業表現，最後，克里斯將詳細介紹我們的財務業績並提供我們 2025 年財務前景的最新資訊。

Let's get to it. Regeneron's performance in the first quarter was mixed with some difficult news related to our retinal franchise offset by encouraging news relating to the rest of our commercial portfolio, as well as advances in our robust pipeline of differentiated clinical candidates.

讓我們開始吧。再生元第一季的業績好壞參半，其中與我們的視網膜特許經營權相關的一些艱難消息被與我們其餘商業產品組合相關的令人鼓舞的消息以及我們強大的差異化臨床候選藥物管線的進展所抵消。

Beginning with EYLEA and EYLEA HD. On a macro basis, in the first quarter of 2025, the overall size of the branded anti-VEGF category contracted due to an increase in the usage of low cost off-label, repackaged Avastin likely driven by patient affordability issues because of a funding gap at copay assistance foundations.

從 EYLEA 和 EYLEA HD 開始。從宏觀角度來看，2025 年第一季度，品牌抗 VEGF 類別的整體規模出現萎縮，原因是低成本非說明書用途、重新包裝的 Avastin 的使用量增加，這可能是由於共付額援助基金會的資金缺口導致患者無法負擔費用。

With respect to EYLEA, first quarter of 2025 US net sales were $736 million, down 39% compared to the first quarter of last year, and down 38% compared to the fourth quarter of 2024. However, physician unit demand decreased by 14% sequentially with the balance of the decline primarily attributable to lower wholesale inventory levels, which ended the quarter in the normal range.

EYLEA方面，2025年第一季美國淨銷售額為7.36億美元，較去年第一季下降39%，較2024年第四季下降38%。然而，醫生單位需求環比下降了 14%，其餘下降主要歸因於批發庫存水準較低，導致本季末處於正常範圍內。

With respect to EYLEA HD in the United States, first quarter of 2025 sales were $307 million, up 54% compared to the first quarter of last year and were essentially flat on a sequential basis. Compared to the fourth quarter of 2024, EYLEA HD physician unit demand grew by 5%, which was offset primarily by a modest wholesaler inventory drawdown.

就美國EYLEA HD而言，2025年第一季的銷售額為3.07億美元，與去年第一季相比成長54%，與上一季基本持平。與 2024 年第四季相比，EYLEA HD 醫師單位需求增加了 5%，但主要被批發商庫存適度減少所抵銷。

On the regulatory front, last Wednesday, we were disappointed with the FDA's decision to issue a complete response letter for our submission seeking approval for the EYLEA HD prefilled syringe. Since receiving the CRL, we have held several teleconferences with the FDA to better understand the contents of the CRL.

在監管方面，上週三，我們對 FDA 決定對我們提交的 EYLEA HD 預充式註射器批准申請發出完整回覆信感到失望。自從收到 CRL 以來，我們已與 FDA 舉行了多次電話會議，以便更好地了解 CRL 的內容。

And believe the key outstanding issue relates to a question posed by the FDA to a third party component supplier. This component supplier has expeditiously responded to FDA requests for information. The CRL did not identify any issues with respect to the safety or efficacy of EYLEA HD, the usability of the device, proposed labeling, or pre-approval inspection findings.

並認為關鍵的未決問題與 FDA 向第三方零件供應商提出的問題有關。該零件供應商已迅速回應 FDA 的資訊請求。CRL 沒有發現與 EYLEA HD 的安全性或有效性、設備的可用性、建議標籤或批准前檢查結果有關的任何問題。

We also recently announced that the FDA had accepted for priority review an sBLA for EYLEA HD to treat macular edema following retinal vein occlusion or RVO and for monthly dosing and approved indications following the use of a priority review voucher.

我們最近也宣布，FDA 已接受 EYLEA HD 的 sBLA 優先審查，用於治療視網膜靜脈阻塞或 RVO 後的黃斑水腫以及每月給藥，並在使用優先審查憑證後批准了適應症。

We believe these product enhancements will strengthen EYLEA HD's position in the competitive anti-VEGF category if approved.

我們相信，如果獲得批准，這些產品增強將加強 EYLEA HD 在競爭激烈的抗 VEGF 類別中的地位。

Moving to Dupixent. First quarter 2025 net product sales grew 20% globally on a constant currency basis versus the first quarter of 2024, reflecting strong growth across all approved indications in all groups, and all age groups, I should say, and in all geographic regions.

轉移到 Dupixent。2025 年第一季度，全球淨產品銷售額以固定匯率計算較 2024 年第一季度增長 20%，反映出所有群體、所有年齡組（應該說）和所有地理區域的所有獲批適應症均實現強勁增長。

In the US, where net product sales grew 19%, Dupixent now leads in both new to brand prescription share and total prescription share across all of its approved indications, with the only exception being chronic spontaneous urticaria or CSU, which was approved by the FDA only 11 days ago.

在美國，Dupixent 的淨產品銷售額成長了 19%，目前在其所有核准適應症中，無論是在新品牌處方藥份額還是總處方藥份額方面都處於領先地位，唯一的例外是慢性自發性蕁麻疹 (CSU)，該藥物僅在 11 天前獲得 FDA 的批准。

The COPD launch in the US continues to gain momentum with prescribers increasingly appreciating the role of Type 2 inflammation in certain patients with COPD coupled with greater urgency to identify and treat eligible patients.

美國的 COPD 藥物推廣勢頭持續增強，處方醫生越來越認識到 2 型發炎在某些 COPD 患者中的作用，同時更加迫切地需要識別和治療符合條件的患者。

Payers are increasingly recognizing the value that Dupixent offers and have implemented broad and favorable coverage decisions for commercial and Medicare patients. With those pieces in place, we now look to drive patient awareness in Dupixent as a new treatment option for COPD through a recently launched direct to consumer campaign.

付款人越來越認識到 Dupixent 提供的價值，並為商業和醫療保險患者實施了廣泛而有利的核保決策。有了這些準備，我們現在希望透過最近發起的直接面向消費者的活動，提高患者對 Dupixent 作為 COPD 的新治療選擇的認識。

Libtayo in the US grew 21% compared to the first quarter of last year and has established itself as a cornerstone therapy for advanced non-melanoma skin cancer, while its share of the lung cancer market continues to increase.

美國的Libtayo與去年第一季相比成長了21%，並已成為晚期非黑色素瘤皮膚癌的基石療法，同時其在肺癌市場的份額也持續增加。

In the highly competitive firstline advanced non-small cell lung cancer market, Libtayo is now second in new to brand prescription share despite launching years after other competing therapies, reflecting its differentiated clinical profile and our commercial strategy.

在競爭激烈的一線晚期非小細胞肺癌市場中，儘管 Libtayo 比其他競爭療法晚推出數年，但現在其新品牌處方藥份額排名第二，這反映了其差異化的臨床特徵和我們的商業策略。

We expect Dupixent, EYLEA HD and Libtayo to continue delivering significant growth for the foreseeable future through additional penetration and approved indications, potential future indications, potential combinations with other pipeline candidates, as well as other potential product enhancements.

我們預計，Dupixent、EYLEA HD 和 Libtayo 將在可預見的未來透過額外的滲透和批准的適應症、潛在的未來適應症、與其他候選藥物的潛在組合以及其他潛在的產品增強繼續實現顯著增長。

Now briefly moving to our pipeline, which now includes approximately 45 product candidates in clinical development. We continue to make significant investments in R&D which have yielded notable progress across several key programs so far this year, including four regulatory approvals and nine regulatory submissions.

現在簡要介紹我們的產品線，目前包括約 45 種處於臨床開發階段的候選產品。我們繼續在研發方面進行大量投資，今年迄今已在多個關鍵項目上取得了顯著進展，包括四項監管批准和九項監管提交。

For the remainder of 2025, we anticipate US regulatory approvals for linvoseltamab in relapsed/refractory multiple myeloma, odronextamab in late line follicular lymphoma, Libtayo in adjuvant CSCC, Dupixent in bullous pemphigoid, as well as differentiated enhancements to the EYLEA HD US label.

對於 2025 年剩餘時間，我們預計美國監管機構將批准 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、Libtayo 用於治療輔助性 CSCC、Dupixent 用於治療大皰性類天皰瘡，以及對 EYLEA HD 美國標籤的差異化增強。

We also now expect to read out pivotal or proof of concept data across programs in immunology, oncology, hematology, internal medicine, and rare diseases, programs that George will discuss in a minute.

我們現在也希望讀出免疫學、腫瘤學、血液學、內科和罕見疾病等領域項目的關鍵數據或概念驗證數據，喬治將在稍後討論這些項目。

In closing, Regeneron remains in a very strong position, scientifically, commercially and financially, enabling us to invest heavily in R&D and deliver scientific breakthroughs, maximize growth opportunities from our inline brands, successfully launch new products and indications, and return capital directly to shareholders through dividends and share repurchases.

最後，再生元在科學、商業和財務方面仍然處於非常強大的地位，這使我們能夠大力投資研發並實現科學突破，最大限度地利用我們內聯品牌的成長機會，成功推出新產品和適應症，並透過股息和股票回購直接向股東返還資本。

We look forward to providing updates on these efforts as we move through the remainder of 2025.

我們期待在 2025 年剩餘時間內提供有關這些努力的最新進展。

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

說完這些，我會把電話轉給喬治。

Thanks, Len.

謝謝，Len。

2025 is shaping up to be an exciting year for advancing our broad and differentiated pipeline, and we look forward to reporting several pivotal or proof of concept data sets from multiple programs.

2025 年將成為我們推進廣泛且差異化產品線的令人興奮的一年，我們期待報告來自多個專案的幾個關鍵或概念驗證資料集。

I'd like to briefly highlight these significant opportunities and discuss additional pipeline advancements, starting with Dupixent, which continues to set a high bar across multiple Type 2 allergic diseases. Earlier this month, Dupixent was approved for the treatment of adults and adolescents with chronic spontaneous urticaria, who remain uncontrolled despite antihistamine treatment.

我想簡要地強調這些重要機遇，並討論其他管道進展，首先是 Dupixent，它繼續為多種 2 型過敏疾病設定高標準。本月初，Dupixent 已獲準用於治療患有慢性自發性蕁麻疹的成人和青少年，這些患者儘管接受抗組織胺治療，病情仍未得到控制。

This approval marks the seventh Type 2 allergic disease for which Dupixent has been approved by the FDA and is the first new treatment option for CSU patients in over a decade. Dupixent was also accepted for priority review for the treatment of bullous pemphigoid with the PDUFA date of June 20.

這項批准標誌著 Dupixent 已獲得 FDA 批准用於治療第七種 2 型過敏性疾病，也是十多年來 CSU 患者的第一個新的治療選擇。Dupixent 也被接受用於治療大皰性類天皰瘡的優先審查，PDUFA 日期為 6 月 20 日。

Bullous pemphigoid represents yet another first in class opportunity for Dupixent, which is the only biologic to achieve significant improvements in disease remission and symptoms in this setting. And finally, Dupixent became the first ever biologic medicine to be approved for COPD in Japan, marking the 45th country in which the COPD indication has been approved.

大皰性類天皰瘡為 Dupixent 帶來了另一個同類藥物中首創的機遇，Dupixent 是唯一一種能顯著改善此類疾病的生物製劑。最後，Dupixent 成為日本第一個獲準用於治療 COPD 的生物藥物，這也是日本第 45 個批准該藥物用於治療 COPD 的國家。

We are eagerly awaiting the pivotal readout for itepekimab, our interleukin-33 antibody for COPD and former smokers regardless of eosinophil levels, with data expected in the middle of 2025. In addition to COPD, we recently initiated a Phase 3 program for itepekimab in chronic rhinosinusitis with nasal polyps, an indication with strong genetic validation as well as a Phase 2 study in chronic rhinosinusitis without nasal polyps.

我們熱切期待伊替派單抗（Itepekimab）的關鍵讀數，伊替派單抗是我們的針對 COPD 和既往吸煙者的白細胞介素 33 抗體，無論嗜酸性粒細胞水平如何，預計數據將於 2025 年中期公佈。除了 COPD 以外，我們最近還啟動了 itepekimab 治療伴有鼻息肉的慢性鼻竇炎的 3 期研究，該適應症已得到強有力的基因驗證，同時我們還啟動了針對不伴有鼻息肉的慢性鼻竇炎的 2 期研究。

In addition, next year, we are expecting proof of concept data for itepekimab in non-cystic fibrosis bronchiectasis.

此外，明年，我們期待獲得伊替米單抗治療非囊性纖維化支氣管擴張的概念驗證數據。

Turning now to oncology efforts. We recently submitted US and EU regulatory filings for Libtayo in adjuvant CSCC where Libtayo became the first immunotherapy to show a benefit in a high-risk population. In early June, these data will be presented in an oral presentation at the American Society of Clinical Oncology, or ASCO annual meeting, highlighting a 68% reduction in the risk of disease recurrence or death compared to placebo with no new safety signals identified.

現在轉向腫瘤學研究。我們最近向美國和歐盟提交了 Libtayo 在輔助 CSCC 治療中的監管文件，其中 Libtayo 成為第一個在高風險族群中顯示出益處的免疫療法。6月初，這些數據將在美國臨床腫瘤學會（ASCO）年會上以口頭報告的形式公佈，重點強調與安慰劑相比，該藥物使疾病復發或死亡的風險降低了68%，且沒有發現新的安全信號。

This data set underscores our belief that Libtayo provides the best in class foundation for combinations with our other oncology assets. And in this regard, Libtayo is being tested in combination with fianlimab, our LAG-3 antibody in several solid tumor settings.

這本資料集強調了我們的信念，即 Libtayo 為與我們其他腫瘤學資產的結合提供了一流的基礎。在這方面，Libtayo 正在與我們的 LAG-3 抗體 fianlimab 聯合在幾種實體瘤環境中進行測試。

In melanoma, early clinical data have suggested that this combination can provide substantial additive benefit compared to PD-1 monotherapy without exacerbating safety. An ongoing Phase 3 trial in firstline metastatic melanoma, evaluating this combination compared to KEYTRUDA monotherapy is expected to read out in the second half of this year.

在黑色素瘤中，早期臨床數據表明，與 PD-1 單一療法相比，這種組合可以提供顯著的附加益處，而不會降低安全性。目前正在進行的針對一線轉移性黑色素瘤的 3 期試驗將評估該組合療法與 KEYTRUDA 單藥療法的療效，預計今年下半年公佈結果。

We reiterate that if these data confirm best in class activity in melanoma, it will increase our confidence for this combination in other cancer settings. In first line advanced non-small cell lung cancer, a pre-planned interim analysis was conducted this month on two ongoing Phase 2 studies evaluating this combination.

我們重申，如果這些數據證實了黑色素瘤中最佳的活性，它將增加我們對這種組合在其他癌症環境中的信心。在一線晚期非小細胞肺癌中，本月對兩項正在進行的評估該組合的 2 期研究進行了預先計劃的中期分析。

Due to limited follow-up, the Phase 2 portion of the studies will continue unchanged until additional data are available. The next analysis for these studies are expected in the first quarter of 2026, in which a decision whether to advance to Phase 3 will be made.

由於後續行動有限，研究的第 2 階段部分將繼續保持不變，直到獲得更多數據。這些研究的下一次分析預計將在 2026 年第一季進行，屆時將決定是否進入第三階段。

No new safety signals were observed in either study.

兩項研究均未觀察到新的安全訊號。

Turning to our CD3 bispecifics. The European Commission recently granted conditional marketing authorization for Lynozyfic, or linvoseltamab, our BCMA by CD3 bispecific for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least three prior therapies, marking Lynozyfic's first global regulatory approval.

轉向我們的 CD3 雙特異性抗體。歐盟委員會最近授予 Lynozyfic（又稱 linvoseltamab）有條件上市許可，該藥物是我們的 BCMA by CD3 雙特異性藥物，用於治療已接受過至少三種先前療法的複發/難治性多發性骨髓瘤成年患者，這標誌著 Lynozyfic 首次獲得全球監管批准。

In the US, our resubmission of the linvoseltamab BLA for relapsed/refractory multiple myeloma was accepted by the FDA with the PDUFA date of July 10. We believe linvoseltamab has the potential to be the best in class BCMA by CD3 bispecific due to its differentiated clinical profile, dosing, and administration.

在美國，我們重新提交的用於治療復發/難治性多發性骨髓瘤的林沃司他單抗生物製品許可申請 (BLA) 已被 FDA 接受，PDUFA 日期為 7 月 10 日。我們相信，由於其差異化的臨床特徵、劑量和給藥方式，林沃司他單抗有可能成為 CD3 雙特異性 BCMA 的最佳產品。

A broad clinical program in earlier lines emphasizes monotherapy and limited combinations and continues to advance with the confirmatory Phase 3 LINKER-MM3 study in relapsed/refractory multiple myeloma now fully enrolled.

早期的廣泛臨床項目強調單一療法和有限的聯合治療，並且隨著復發/難治性多發性骨髓瘤的驗證性 3 期 LINKER-MM3 研究的繼續推進，目前該研究已完全招募患者。

At ASCO, also in oral presentations, we will present initial results from the Phase 1/2 LINKER-MM2 trial, evaluating linvoseltamab in combinations with carfilzomib, and with bortezomib in patients with relapsed/refractory multiple myeloma.

在 ASCO 上，我們也將以口頭報告的形式介紹 1/2 期 LINKER-MM2 試驗的初步結果，該試驗評估了林沃司他單抗與卡非佐米以及硼替佐米聯合治療復發/難治性多發性骨髓瘤患者的療效。

Both combinations demonstrate a high rate of deep and durable responses with a safety profile consistent with the individual drugs, supporting further development.

兩種組合均表現出高深度和持久的反應率，其安全性與單一藥物一致，並支持進一步開發。

Over to our next demand, our CD20 by CD3 bispecific. The FDA has accepted the BLA resubmission for relapsed/refractory follicular lymphoma with a PDUFA date of July 30. Odronextamab has demonstrated potentially best in class efficacy in this late-line setting and our differentiated clinical development focuses on monotherapy and limited novel combinations in earlier line and continues to advance.

我們的下一個需求是 CD20 和 CD3 雙特異性。FDA 已接受復發/難治性濾泡性淋巴瘤的 BLA 重新提交，PDUFA 日期為 7 月 30 日。Odronextamab 已證明在這種後期治療環境中具有潛在的最佳療效，而我們的差異化臨床開發則側重於早期治療中的單一療法和有限的新型組合，並且仍在繼續推進。

Turning to hematology. We are rapidly advancing our Factor XI program, where we are investigating two different antibodies that target different Factor XI domains to create a tailored approach to anticoagulation, offering the potential for improved blood clot prevention and lower bleeding risk.

轉向血液學。我們正在快速推進我們的 XI 因子計劃，我們正在研究針對不同 XI 因子結構域的兩種不同抗體，以創建一種定制的抗凝血方法，從而有可能改善血栓預防並降低出血風險。

We remain on track to enroll patients in pivotal studies this year, both in settings with large patient populations and longer follow-up, as well as in settings with smaller populations and shorter follow-up. They may provide a quicker path to market.

我們今年仍將按計畫招募患者參與關鍵研究，既包括患者人數眾多、追蹤時間較長的環境，也包括患者人數較少、追蹤時間較短的環境。它們或許能提供一條更快速的市場途徑。

Moving to our obesity efforts. Regeneron has decades of experience in muscle biology, growth factors, signaling pathways and genetics. We are capitalizing on this expertise to position ourselves as a key player in the rapidly expanding obesity market by investigating agents that enhance GLP-1 weight loss by maintaining muscle mass.

轉向我們的肥胖問題努力。Regeneron 在肌肉生物學、生長因子、訊號路徑和遺傳學方面擁有數十年的經驗。我們正在利用這些專業知識，透過研究透過維持肌肉質量來增強 GLP-1 減肥效果的藥物，將自己定位為快速擴張的肥胖症市場中的關鍵參與者。

Our muscle-sparing Phase 2 COURAGE study is investigating the addition of Trevogrumab, our GDF8 antibody to semaglutide, with and without garetosmab, our anti-activin antibody with the goal of improving the quality of weight loss.

我們的保留肌肉的 2 期 COURAGE 研究正在研究將 Trevogrumab（我們的 GDF8 抗體）添加到 semaglutide 中，並聯合或不聯合使用 garetosmab（我們的抗激活素抗體），目的是提高減肥品質。

We expect to report data for the 26 week primary endpoints, including percentage of weight loss and percentage of fat loss compared to baseline in the second half of this year. At the upcoming American Diabetes Association meeting in June, we anticipate that LLY will present Phase 2 data from a very related program evaluating semaglutide combined with an antibody that binds to activin Type 2 receptors, which blocks myostatin and activin signaling.

我們預計將在今年下半年報告 26 週主要終點的數據，包括與基線相比的體重減輕百分比和脂肪減輕百分比。在即將於 6 月舉行的美國糖尿病協會會議上，我們預計 LLY 將展示一項非常相關的計劃的第 2 階段數據，該計劃評估了司美格魯肽與一種結合激活素 2 型受體的抗體的結合，從而阻斷了肌生長抑制素和激活素信號傳導。

The weight loss, lean mass preservation, and overall metabolic profile, along with safety and tolerability, will help inform next steps for our programs as well.

體重減輕、瘦體重維持和整體代謝狀況以及安全性和耐受性也將有助於指導我們計劃的下一步。

And finally, moving to our Regeneron Genetics medicines pipeline. Our novel C5 siRNA and antibody combination has demonstrated rapid, complete, and uninterrupted inhibition of C5, as seen in an ongoing pivotal program in patients with paroxysmal nocturnal hemoglobinuria.

最後，轉向我們的再生元遺傳藥物管道。我們的新型 C5 siRNA 和抗體組合已證明能夠快速、完全且不間斷地抑制 C5，正如陣發性睡眠性血紅蛋白尿症患者正在進行的關鍵計劃中所見。

These profound findings increase our confidence in seeing robust improvement in generalized myasthenia gravis, where pivotal results from an ongoing Phase 3 program are expected in the second half of this year. A unique mechanism of action provides more complete C5 inhibition than observed with other C5 approaches that are approved in this indication, as well as the potential for more convenient subcutaneous regimens.

這些意義深遠的發現增強了我們對全身性重症肌無力得到顯著改善的信心，正在進行的第三階段計劃的關鍵結果預計將在今年下半年出現。獨特的作用機制提供了比在此適應症中批准的其他 C5 方法更完全的 C5 抑制，以及更方便的皮下治療方案的潛力。

In summary, Regeneron continues to deliver scientific firsts and drive innovation. Our unique R&D capabilities have allowed us to build one of the most prolific pipelines in our industry, and we look forward to reporting multiple impactful readouts later this year.

總而言之，Regeneron 繼續實現科學突破並推動創新。我們獨特的研發能力使我們能夠建立行業內最豐富的管道之一，我們期待在今年稍後報告多個有影響力的讀數。

With that, let me turn it over to Marion.

說完這些，讓我把話題交給馬里恩。

Thank you, George.

謝謝你，喬治。

Despite a challenging environment in the first quarter, our commercial teams are positioned to capitalize on multiple near-term opportunities across the portfolio, including product enhancements and launches of both new medicines and new indications for previously approved medicines.

儘管第一季環境充滿挑戰，但我們的商業團隊仍準備好利用整個產品組合中的多個近期機遇，包括產品增強以及新藥和先前批准藥物的新適應症的推出。

Looking to the future, as George highlighted, our pipeline is poised to deliver the next wave of significant commercial opportunities that may provide innovative medicines to even more patients. Beginning with our first quarter results for EYLEA HD and EYLEA , combined US net sales were $1.04 billion, down 30% sequentially, primarily reflecting lower wholesaler inventory levels for both products, which declined during the quarter to the normal range, as well as continued competitive pressures.

展望未來，正如喬治所強調的，我們的產品線將帶來下一波重大商業機會，為更多患者提供創新藥物。從 EYLEA HD 和 EYLEA 第一季業績開始，美國合併淨銷售額為 10.4 億美元，環比下降 30%，主要反映了這兩種產品的批發商庫存水平較低，在本季度下降至正常範圍，以及持續的競爭壓力。

In aggregate sequential physician unit demand for EYLEA HD and EYLEA declined by 11%. We believe there was a significant negative impact in the branded anti-VEGF category due to an ongoing funding gap at not-for-profit patient assistance foundations that provide copay support for eligible patients with retinal diseases.

整體而言，EYLEA HD 和 EYLEA 的醫師單位需求量連續下降了 11%。我們認為，由於為符合條件的視網膜疾病患者提供共付額支持的非營利性患者援助基金會持續存在資金缺口，品牌抗 VEGF 類別受到了顯著的負面影響。

Consequently, low cost off-label repackaged Avastin increased its anti-VEGF category share by approximately 6 percentage points to 32%. Despite these challenges, EYLEA HD and EYLEA captured 41% of the anti-VEGF category, maintaining market leadership.

因此，低成本的非說明書重新包裝的 Avastin 使其抗 VEGF 類別份額增加了約 6 個百分點，達到 32%。儘管面臨這些挑戰，EYLEA HD 和 EYLEA 仍佔了抗 VEGF 類別的 41%，維持了市場領先地位。

For the first quarter, EYLEA US net sales were $736 million, primarily due to lower wholesaler inventory levels, lower physician demand, as well as increased competition. While we expect competitive pressures for EYLEA to persist, our focus remains on promoting the ongoing adoption of EYLEA HD, which has the potential to become the new standard of care.

第一季度，EYLEA 美國淨銷售額為 7.36 億美元，主要原因是批發商庫存水準下降、醫生需求下降以及競爭加劇。雖然我們預計 EYLEA 的競爭壓力將持續存在，但我們的重點仍然是推動 EYLEA HD 的持續採用，它有可能成為新的護理標準。

EYLEA HD was the only branded medicine in the anti-VEGF category to maintain US net sales quarter over quarter, achieving $307 million and growing 54% year over year. In August, we anticipate potential FDA approvals of EYLEA HD in retinal vein occlusion and for every four week dosing across all approved indications.

EYLEA HD 是抗 VEGF 類別中唯一一款美國淨銷售額維持較上季成長的品牌藥物，達到 3.07 億美元，較去年同期成長 54%。我們預計 8 月 FDA 將批准 EYLEA HD 用於治療視網膜靜脈阻塞，並批准其用於所有核准適應症的每四週給藥。

If approved in RVO, EYLEA HD would be the first and only treatment that can be dosed up to every eight weeks, which is twice as long as any other product in the category. In addition, with the potential approval of every four week dosing, EYLEA HD would offer physicians the most flexible dosing options in the category.

如果在 RVO 獲得批准，EYLEA HD 將成為第一個也是唯一一個可以每八週服用一次的治療方法，這是同類產品中給藥時間的兩倍。此外，隨著每四周給藥一次的潛在批准，EYLEA HD 將為醫生提供同類產品中最靈活的給藥選擇。

With these label enhancements and anticipated approval of the prefilled syringe, we expect to see an acceleration in EYLEA HD demand.

隨著這些標籤的增強和預充式註射器的預期批准，我們預計 EYLEA HD 的需求將會加速成長。

And now to Dupixent. In the first quarter, Dupixent achieved global net sales of $3.7 billion, representing a 20% year over year increase on a constant currency basis. In the US, net sales grew 19% to $2.6 billion based on robust demand across all approved indications.

現在來看看 Dupixent。第一季度，Dupixent 實現全球淨銷售額 37 億美元，以固定匯率計算年增 20%。在美國，由於所有核准適應症的強勁需求，淨銷售額成長 19%，達到 26 億美元。

In the first quarter, US net price was unfavorably impacted by the annual reset of commercial insurance deductibles and the implementation of Medicare Part D redesign. Dupixent continues to live up to its potential to dramatically improve patients' lives with approvals in seven indications, four of which have achieved blockbuster status globally.

第一季度，美國淨價格受到商業保險免賠額年度重置和醫療保險D部分重新設計的實施的不利影響。Dupixent 繼續發揮其顯著改善患者生活的潛力，已獲得七項適應症的批准，其中四種已在全球範圍內取得重磅藥物地位。

Dupixent's unique mechanism of action makes it the only medicine that addresses the underlying drivers of disease and treats multiple comorbid Type 2 conditions. Despite increasing competition in established indications, Dupixent remains the market leader.

Dupixent 獨特的作用機制使其成為唯一能夠解決疾病根本驅動因素並治療多種合併症 2 型疾病的藥物。儘管在既定適應症領域的競爭日益激烈，Dupixent 仍然是市場領導者。

In atopic dermatitis, increased promotional spend from competitors has accelerated market growth, with Dupixent continuing to capture the vast majority of new patients. In asthma, Dupixent continues to lead all biologics, and new to brand share and is now the category leader in total prescriptions.

在異位性皮膚炎領域，競爭對手增加促銷支出加速了市場成長，Dupixent 持續吸引絕大多數新患者。在氣喘領域，Dupixent 繼續領先所有生物製劑，並成為新品牌份額，目前是總處方類別的領導者。

Momentum in new indications continues to build, and COPD uptake is accelerating. Most pulmonologists have extensive experience in prescribing Dupixent for asthma and are increasingly prescribing it for COPD. Many have remarked on Dupixent's ability to reduce exacerbations, rapidly and meaningfully improve lung function, and reduce the need for oxygen therapy.

新適應症的勢頭持續增強，COPD 的吸收正在加速。大多數肺科醫生在使用 Dupixent 治療氣喘方面擁有豐富的經驗，並且越來越多地使用該藥物來治療 COPD。許多人都對 Dupixent 減少病情惡化、快速且顯著改善肺功能以及減少氧氣治療需求的能力發表了評論。

With physician and patient awareness building and strong reimbursement established, the COPD launch has outperformed all other Dupixent indication launches in cumulative new to brand prescriptions with the exception of atopic dermatitis.

隨著醫生和患者意識的提高以及強有力的報銷機制的建立，COPD 的上市在累計新品牌處方方面已經超過了除特應性皮膚炎之外的所有其他 Dupixent 適應症的上市。

Earlier this month, Dupixent was approved to treat patients with chronic spontaneous urticaria, or CSU, where we estimate there are more than 300,000 patients in the US with a disease inadequately controlled by antihistamines.

本月初，Dupixent 已獲準用於治療慢性自發性蕁麻疹 (CSU) 患者，我們估計美國有超過 30 萬名患者患有這種疾病，但抗組織胺無法充分控制。

Dupixent is the first new targeted treatment for CSU in over 10 years, providing a new treatment for patients that previously had limited options. The launch is underway, and early feedback has been favorable. Our Dupixent team is also preparing for potential approval in bullous pemphigoid, which would represent the fourth approval in a chronic and debilitating skin disease driven by Type 2 inflammation.

Dupixent 是十多年來首個針對 CSU 的新型標靶治療方法，為先前選擇有限的患者提供了新的治療方法。此次發布正在進行中，早期反饋良好。我們的 Dupixent 團隊也正在為大皰性類天皰瘡的潛在批准做準備，這將是由 2 型發炎引起的慢性和衰弱性皮膚病的第四次批准。

Nearly 30,000 adults in the US suffer from this difficult to treat condition where current care is limited to corticosteroids and immunosuppressants. These treatments have poor clinical efficacy as well as safety concerns, particularly in older patients.

美國有近 3 萬名成年人患有這種難以治療的疾病，目前的治療方法僅限於皮質類固醇和免疫抑制劑。這些治療方法臨床療效較差，且有安全隱患，尤其是對老年患者而言。

If approved, Dupixent would be the first and only targeted medicine to treat this disease. In summary, Dupixent is now firmly established as the standard of care across a range of Type 2 conditions and has substantial growth opportunities in both existing and new indications.

如果獲得批准，Dupixent 將成為第一個也是唯一一個治療該疾病的標靶藥物。總而言之，Dupixent 現已牢固確立為一系列 2 型疾病的治療標準，並且在現有和新適應症中都具有巨大的成長機會。

Turning now to Libtayo. First quarter, global net sales grew 8% year over year on a constant currency basis to $285 million with US net sales reaching $193 million, up 21%. First quarter results reflect typical seasonality dynamics in the timing of shipments and lower inventory levels.

現在轉向 Libtayo。第一季度，全球淨銷售額以固定匯率計算年增 8%，達到 2.85 億美元，其中美國淨銷售額達到 1.93 億美元，成長 21%。第一季的業績反映了出貨時間和庫存水準較低的典型季節性動態。

In the US, demand continues to increase across both non-melanoma skin cancer indications, and lung cancer, and we are seeing growth in approved indications internationally. We look forward to the potential FDA approval of Libtayo for adjuvant treatment of high risk cutaneous squamous cell carcinoma, where we estimate there are approximately 10,000 patients in the US who may benefit from this treatment.

在美國，非黑色素瘤皮膚癌和肺癌的需求持續增長，我們看到國際上批准的適應症也在增長。我們期待 FDA 批准 Libtayo 用於高風險皮膚鱗狀細胞癌的輔助治療，我們估計美國約有 10,000 名患者可能受益於這種治療。

Our oncology teams are excited about the potential to launch two new hematology products later this year, linvoseltamab in relapsed/refractory multiple myeloma and odronextamab in relapsed/refractory follicular lymphoma.

我們的腫瘤學團隊對今年稍後推出兩種新的血液學產品感到非常興奮，即用於治療復發/難治性多發性骨髓瘤的 linvoseltamab 和用於治療復發/難治性濾泡性淋巴瘤的 odronextamab。

Both have demonstrated best in class clinical profiles in these later line settings.

兩者均在後期設置中展現出一流的臨床特性。

In summary, our commercial portfolio is well-positioned to capitalize on many near term growth opportunities, enabling us to deliver more treatments to more patients.

總之，我們的商業組合處於有利地位，可以利用許多近期的成長機會，使我們能夠為更多患者提供更多治療。

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

說完這些，我會把電話轉給克里斯。

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. First quarter of 2025 total revenues were $3 billion inclusive of higher Sanofi collaboration revenue driven by Dupixent growth and higher US net sales of EYLEA HD compared to the prior year.

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。2025 年第一季總營收為 30 億美元，其中包括受 Dupixent 成長推動的賽諾菲合作收入增加以及 EYLEA HD 美國淨銷售額較上年同期增加。

First quarter diluted debt income per share was $8.22 on net income of $928 million. Beginning with collaboration revenue, revenues from the Sanofi collaboration were approximately $1.2 billion, of which $1 billion related to our share of collaboration profits.

第一季每股攤薄債務收益為 8.22 美元，淨收益為 9.28 億美元。從合作收入開始，賽諾菲合作的收入約為 12 億美元，其中 10 億美元與我們的合作利潤份額有關。

Regeneron's share of profits grew 27% versus the prior year driven by volume growth through Dupixent and higher collaboration margins. The Sanofi development balance was approximately $1.5 billion at the end of the first quarter, reflecting a reduction of approximately $180 million from the end of 2024.

由於 Dupixent 的銷售成長和更高的合作利潤率，Regeneron 的利潤份額較上年增長了 27%。第一季末，賽諾菲開發餘額約 15 億美元，較 2024 年底減少約 1.8 億美元。

Moving to Bayer. First quarter net sales of EYLEA and EYLEA 8 mg outside the US were $858 million, up 5% versus the prior year on a constant currency basis and inclusive of $146 million of EYLEA 8 mg sales. Total Bayer collaboration revenue was $344 million of which $317 million were related to our share of net profits outside the US.

轉投拜耳。第一季度，EYLEA 和 EYLEA 8 毫克在美國以外的淨銷售額為 8.58 億美元，以固定匯率計算比上年增長 5%，其中包括 1.46 億美元的 EYLEA 8 毫克銷售額。拜耳合作總收入為 3.44 億美元，其中 3.17 億美元與我們在美國以外的淨利潤份額有關。

Now to our operating expenses. R&D expense was $1.2 billion in the first quarter. Modest growth versus the prior year was driven by continued investments to support Regeneron's innovative pipeline, including higher personnel expenses and clinical manufacturing costs.

現在談談我們的營運費用。第一季研發支出為12億美元。與前一年相比，溫和的成長得益於對再生元創新管道的持續投資，包括更高的人員費用和臨床製造成本。

First quarter SG&A was $537 million, down 8% from the prior year. The decline was driven by lower general and administrative expenses while selling expenses were flat year over year. First quarter 2025 gross margin on net product sales was 85%.

第一季銷售、一般及行政費用為 5.37 億美元，較上年下降 8%。下降的原因是一般及行政開支下降，而銷售開支較去年同期持平。2025 年第一季淨產品銷售毛利率為 85%。

The lower gross margin versus the prior year reflects higher inventory write-offs in the first quarter of 2025 and a changing product mix. Our effective tax rate increased versus the prior year, primarily driven by a lower benefit from stock-based compensation deductions.

與去年相比，毛利率較低反映了 2025 年第一季庫存註銷增加以及產品組合變化。我們的有效稅率較前一年增加，主要原因是股票薪資扣除收益減少。

Regeneron generated $816 million in free cash flow in the first quarter and ended the quarter with cash and marketable securities of $17.6 billion and debt of approximately $2.7 billion. We continue to monitor developments regarding pharmaceutical sector tariffs.

再生元在第一季產生了 8.16 億美元的自由現金流，本季末的現金和有價證券為 176 億美元，債務約為 27 億美元。我們將繼續關注製藥業關稅的發展。

While we do not expect previously enacted tariffs to have a material impact on our business, any potential impact from sector-specific tariffs is not quantifiable at this time due to uncertainty around the details of implementation.

雖然我們預計先前頒布的關稅不會對我們的業務產生重大影響，但由於實施細節的不確定性，目前無法量化特定行業關稅的任何潛在影響。

Regardless of any potential tariffs, Regeneron has always been committed to making significant investments in the United States to expand our R&D and manufacturing capabilities. We recently announced a new agreement with FUJIFILM, Diosynth Biotechnologies in North Carolina to invest over $3 billion to nearly double our US large scale manufacturing capacity.

無論任何潛在的關稅，再生元始終致力於在美國進行大量投資，以擴大我們的研發和製造能力。我們最近宣布與北卡羅來納州的富士膠片 Diosynth Biotechnologies 達成一項新協議，投資超過 30 億美元，使我們在美國的大規模製造能力幾乎翻倍。

This agreement, along with our $3.6 billion expansion of our Tarrytown, New York R&D and preclinical manufacturing facilities, our fill/finish facility in Rensselaer, New York, and the acquisition of an additional property in Saratoga Springs, New York represent planned US investments of over $7 billion.

該協議，加上我們斥資 36 億美元擴建位於紐約州塔里敦的研發和臨床前製造設施、位於紐約州倫斯勒的灌裝/完成設施以及收購位於紐約州薩拉託加溫泉的另一處房產，代表著計劃在美國投資超過 70 億美元。

These investments will enable us to continue to grow in the US and support a differentiated R&D engine while significantly increasing our ability to manufacture both clinical and commercial supply. Beyond these investments, we continue to return capital to shareholders in the first quarter both through share repurchases and the payment of our recently initiated quarterly dividend.

這些投資將使我們能夠在美國繼續發展並支援差異化的研發引擎，同時顯著提高我們製造臨床和商業供應的能力。除了這些投資之外，我們還在第一季繼續透過股票回購和支付最近開始的季度股息向股東返還資本。

We repurchased approximately $1.1 billion worth of our shares in the first quarter with approximately $3.9 billion remaining available for share repurchases as of March 31. We continue to see share repurchases as an efficient use of capital and remain opportunistic buyers of our shares.

我們在第一季回購了價值約 11 億美元的股票，截至 3 月 31 日，剩餘約 39 億美元可供回購。我們仍然認為股票回購是資本的有效利用方式，並將繼續作為我們股票的機會主義買家。

In addition to share repurchases, our newly initiated dividend program allows us increased flexibility to return capital to shareholders. We paid our first quarterly dividend last month, and the Board of Directors has declared the next dividend of $0.88 per share, which will be paid in June.

除了股票回購之外，我們新啟動的股利計畫還使我們能夠更靈活地向股東返還資本。我們上個月支付了第一筆季度股息，董事會宣布下一筆股息為每股 0.88 美元，並將於 6 月支付。

Finally, we have updated our 2025 gross margin guidance to be in the range of 86% to 87%. This change is primarily driven by higher than expected inventory write-offs in the first quarter. A full summary of our latest guidance can be found in our press release issued earlier this morning.

最後，我們已更新 2025 年毛利率預期，至 86% 至 87% 之間。這項變化主要是由於第一季庫存注銷售量高於預期所致。我們最新指南的完整摘要可在我們今天早上發布的新聞稿中找到。

In conclusion, Regeneron's strong financial position will allow us to continue to invest in our differentiated R&D capabilities and pipeline to deliver new medicines to patients and long-term value to shareholders.

總之，再生元強大的財務狀況將使我們能夠繼續投資於差異化的研發能力和產品線，為病患提供新藥，並為股東帶來長期價值。

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

說完，我會把電話轉回給瑞安。

Thank you, Chris.

謝謝你，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.

我們現在開始問答環節。

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.

為了確保我們能夠解答盡可能多的問題，我們將先回答每個來電者的一個問題，然後再回答下一個問題。

Josh, can we go to the first question, please?

喬希，我們可以開始第一個問題嗎？

Tyler Van Buren, TD Cowen.

泰勒範布倫 (Tyler Van Buren)，TD Cowen。

Regarding the EYLEA HD CRL for the prefilled syringe, can you elaborate further on the question posed by the FDA? And perhaps more importantly, compare the situation to the original EYLEA HD CRL as that speed to resolution was very quick, about 2.5 months if I'm not mistaken, which would still be ahead of the RVO in every four week dosing PDUFA in August.

關於預充式註射器的 EYLEA HD CRL，能否進一步闡述 FDA 提出的問題？或許更重要的是，將情況與原始的 EYLEA HD CRL 進行比較，因為其解決速度非常快，如果我沒記錯的話大約是 2.5 個月，這仍然領先於 8 月份每四周給藥一次的 RVO PDUFA。

Right. It's Len speaking.

正確的。我是 Len。

I think you have to understand a little bit of detail on the processes and what happens. And that when you're reviewing -- when the FDA is reviewing your submission for an approval of a new device, we don't necessarily make all the components and in this case, we don't make all the components.

我認為你必須了解有關流程和所發生情況的一些細節。當您審查時 - 當 FDA 審查您提交的新設備批准文件時，我們不一定會生產所有組件，在這種情況下，我們不會生產所有組件。

You might be buying a stopper from somebody, some glass from somebody else, a needle from somebody else, and so forth. And we have the design and then we have an assembly. When the FDA has questions about one of the components, it's -- that's what it's referred to as a drug master file.

您可能從某人那裡購買一個塞子，從其他人那裡購買一些玻璃，從其他人那裡購買一根針等等。我們有設計，然後進行組裝。當 FDA 對某個組件有疑問時，這就是所謂的藥物主文件。

They go to the holder of that drug master file. Let's say it's somebody who makes one of the components. The FDA has a question, well, how do you guys do this? And then the holder of the master file responds to the FDA.

它們會交給藥品主文件的持有者。假設某人製造了其中一個組件。FDA 有一個問題，那麼，你們是如何做到這一點的呢？然後主文件持有者向 FDA 回應。

By rule, we are not partied to that up and back between the FDA and the third party component supplier. The reason we're not partied is because most of the time, these questions relate to general practices where in which the supplier is not only supplying Regeneron, they might be supplying 20 other pharmaceutical companies, which is in fact the case in some of these DMFs we're dealing with here.

根據規定，我們不參與 FDA 與第三方零件供應商之間的往來。我們之所以沒有參與其中，是因為大多數時候，這些問題與一般做法有關，即供應商不僅向 Regeneron 供貨，還可能向其他 20 家製藥公司供貨，事實上，我們在此處理的一些 DMF 就是這種情況。

So that's the general tone of things. The questions get asked. In this particular case, based on our phone calls, after we received the CRL last Wednesday, we realized that nobody had gotten these questions until the day of the CRL or the day before or literally after the CRL.

這就是事情的整體基調。問題被提出。在這個特殊情況下，根據我們的電話記錄，在我們上週三收到 CRL 後，我們意識到直到 CRL 當天或 CRL 前一天或之後才有人收到這些問題。

In any case, based on our conversation with the FDA, we believe that there's one key issue that is left to resolve. There are a few other minor ones which I think were just clarifications, but the one key issue relates to a supplier.

無論如何，根據我們與 FDA 的對話，我們認為還有一個關鍵問題需要解決。還有一些其他的小問題，我認為只是澄清一下，但一個關鍵問題與供應商有關。

And the supplier has told us that the FDA asked for some data. They have all the data. They expeditiously supplied it. Now of course, we don't know the data because we can't be involved by rule in that process. We take it, that word that they think that they have satisfied the agency.

供應商告訴我們 FDA 要求提供一些數據。他們擁有所有數據。他們迅速地提供了它。現在當然我們不知道數據，因為我們無法透過規則參與過程。我們認為，他們認為他們已經滿足了該機構的要求。

Of course, the FDA has to review this. They could be up and back. You said this. Well, we really wanted that. Maybe you have more of this, and so forth. So that leads to a little bit of uncertainty on how fast this could all get resolved.

當然，FDA 必須對此進行審查。他們可以來回走動。你這麼說。嗯，我們確實想要這個。也許您還有更多這樣的情況，等等。因此，對於這個問題能多快解決，存在一些不確定性。

We do have commitments from the FDA that they will move expeditiously as well. That doesn't mean they'll approve it. But they will review quickly the data that's submitted and have an up and back because they recognize, I think, the importance in advance of the prefilled syringe being a better way of administering the product than that of a vial for patients getting intravitreal injections.

我們確實得到了 FDA 的承諾，他們也會迅速採取行動。這並不意味著他們會批准它。但他們會快速審查提交的數據並進行複核，因為我認為他們提前認識到預充式註射器對於接受玻璃體內注射的患者來說是一種比小瓶更好的給藥方式。

So boil all that down, how long can this take? It could go quickly, as you said. The last time this happened, it took a few months. It could go longer. We don't think there's a reinspection involved. It's not an issue related to that.

那麼歸結起來，這需要多長時間？正如您所說，它可以很快完成。上次發生這種情況時，花了幾個月的時間。它可以持續更長時間。我們認為不需要重新檢查。這不是與此相關的問題。

So we don't think there will be these internal long timelines for that. But we'll know more in the coming weeks or months. And we will hopefully get it across the finish line in a short while. But we'll try and keep you posted once we know what the FDA is really up to.

因此，我們認為不會有這樣的內部長期時間表。但在接下來的幾週或幾個月內我們就會知道更多。我們希望很快就能完成它。但一旦我們了解 FDA 的真實動向，我們會盡力及時通知您。

I'm sorry that that's a little indefinite, Tyler, but that's the nature of the process.

抱歉，泰勒，這個問題有點不確定，但這就是過程的本質。

Let's move to the next question, please, Josh.

喬希，請讓我們進入下一個問題。

Alexandria Hammond, Wolfe Research.

亞歷山大‧哈蒙德，沃爾夫研究公司。

I want to pivot a little bit, and I'm curious on the pipeline. So on your factor XI antibodies, how you prioritize which indications to go after? And how should we think about the timing of launches? Can you provide any follow up to on your discussions with regulatory authorities on aligning trial design?

我想稍微轉變一下，我對管道很好奇。那麼對於您的 XI 因子抗體，您如何確定優先治療哪些適應症？我們該如何考慮發射時機？您能否提供與監管機構就協調試驗設計進行討論的後續資訊？

How do we prioritize -- I couldn't hear --

我們如何決定優先順序——我聽不清楚--

Factor XI indications.

因子 XI 適應症。

Indications. Well, we're doing a combination of indications that are maybe to be expected and will take a little bit longer, as well as some indications that we haven't disclosed that we think we might be able to get across the finish line sooner.

適應症。嗯，我們正在進行一些可能在意料之中、需要更長的跡象，以及一些我們尚未透露的跡象，我們認為我們可能能夠更快地完成任務。

In terms of our approaches, what we're trying to prioritize are indications and studies where we'll be able to show the benefit not only of the anticoagulation profile but of the differentiated bleeding risk profile of both of these antibodies.

就我們的方法而言，我們試圖優先考慮的是適應症和研究，我們不僅能夠展示抗凝血特性的益處，還能展示這兩種抗體的差異化出血風險特性的益處。

And the hope is to actually show that one or both of these antibodies have very favorable anticoagulations as well as substantially lower bleeding risks than available options for patients. So we haven't disclosed all the indications.

我們希望能夠真正證明，這些抗體中的一種或兩種都具有非常有利的抗凝血作用，且出血風險比患者可用的選擇要低得多。所以我們還沒有透露所有的跡象。

We haven't shown the timing of them. But there's a variety of them. And there -- some of them will be coming in sooner. Some of them will be taking a little bit longer. And we hope that they will be emphasizing, as I said, the potential for really addressing what's holding back a lot of patients in this field from receiving anticoagulation therapy, which is minimizing the bleeding risk that these people invariably suffer from.

我們還沒有展示它們的時間。但它們有很多種。其中一些人將會更早到達。其中一些會花費更長的時間。正如我所說，我們希望他們能夠強調真正解決阻礙該領域許多患者接受抗凝血治療的原因，從而最大限度地降低這些人必然會遭受的出血風險。

As we've announced, we are beginning to enroll Phase 3 studies this year.

正如我們所宣布的，我們今年將開始招募第三階段的研究。

Let's move to the next question, please.

請讓我們進入下一個問題。

Chris Schott, JPMorgan.

摩根大通的克里斯·肖特。

I just had one on EYLEA and the foundation funding. I appreciate the color on the call, but just any updated thoughts on when we could think about the foundation reopening and how quickly once it's reopened, we could think about some of these volumes moving from the generic Avastin back to branded agents?

我剛剛收到一份關於 EYLEA 和基金會資助的報告。我很欣賞電話中的精彩內容，但您是否有任何最新的想法，例如我們何時可以考慮重新開放基金會，以及基金會重新開放後，我們可以多快考慮將其中一些藥物從通用 Avastin 轉回品牌代理？

Chris, thanks for the question.

克里斯，謝謝你的提問。

Just for the benefit of everybody, let me just remind everybody how all this works. When you're under commercial insurance and you're younger than 65, if you have a copay in your insurance program, sponsors that people like Regeneron can directly to a patient supply copay assistance in the form of a coupon, et cetera, et cetera.

為了大家的利益，讓我提醒大家這一切是如何運作的。當您參加商業保險並且年齡小於 65 歲時，如果您的保險計劃中有共付額，那麼像 Regeneron 這樣的贊助商可以直接以優惠券的形式向患者提供共付額援助，等等。

When a patient turns 65 and if they go on Medicare, which most of our patients getting intravitreal injections are, those patients that are responsible for a copay, typically around 20% if they're in plain old Medicare, it varies somewhat if they're in Medicare Advantage.

當患者年滿 65 歲時，如果他們加入醫療保險，那麼我們接受玻璃體內注射的大多數患者都需要承擔共付額，如果他們加入的是普通醫療保險，則共付額通常約為 20%，如果他們加入的是醫療保險優勢計劃，則共付額會有所不同。

Some people -- many people have insurance, supplemental gap insurance, AARP, whatever you want to call it, which covers these copays. But there are still others who don't have the insurance and can't afford the copay associated with an injection of an anti-VEGF agent, for example.

有些人－許多人都有保險，補充差額保險，AARP，無論你想怎麼稱呼它，它都涵蓋了這些共付額。但還有一些人沒有保險，無法承擔注射抗 VEGF 藥物相關的共付額。

The government has indicated that companies can be part of this safety net, if you will, to help patients who need financial assistance. And the way this works is that companies and others can support independent charitable foundations who then assist patients with retinal disease regardless of the drug they need.

政府表示，如果願意的話，公司可以成為這個安全網的一部分，以幫助需要經濟援助的病人。其運作方式是，公司和其他機構可以支持獨立的慈善基金會，然後這些基金會為患有視網膜疾病的患者提供幫助，無論他們需要什麼藥物。

The foundations take in financially eligible patients and give out the assistance that they can afford to give out on a first come, first serve basis. And so there is no direct relationship. If we give money to a foundation, it could go to support VABYSMO. It could go to support PAVBLU. It could go to support EYLEA.

該基金會接收符合經濟條件的患者，並以先到先得的原則提供力所能及的援助。因此沒有直接關係。如果我們向基金會捐款，這些錢可以用來支持 VABYSMO。它可以用來支援 PAVBLU。它可以用來支援EYLEA。

It could go to support -- in fact, in these funds, as they're constructed today, it could go to support the drugs for geographic atrophy. There's no connection as there shouldn't be in what we give and then what the -- how the foundations dole out the resources.

它可以用來支持——事實上，在今天建立的這些基金中，它可以用來支持治療地理性萎縮的藥物。我們捐贈什麼和基金會如何分配資源之間不應該有連結。

We would like to help as many patients as we can. It turns out we -- was the if not the sole, the vast supporter of these foundations in the recent history. We're talking about having given large sums of money in the neighborhood of over $400 million last year to do this charitable work.

我們希望盡力幫助盡可能多的患者。事實證明，在近代史上，我們是這些基金會的最大支持者，即便不是唯一的支持者。我們說的是，去年我們已經捐贈了超過 4 億美元的大筆資金來做這項慈善工作。

As our commercial outlook in the field has changed, as our resources have changed, we looked at this and said, we'd like to continue doing this, but we can't do it all ourselves. We'd like to help as many people as possible.

隨著我們在該領域的商業前景發生變化，隨著我們的資源發生變化，我們對此表示，我們想繼續這樣做，但我們不能自己做所有的事情。我們希望幫助盡可能多的人。

And so we're trying to come up with a way where others and Regeneron could make sure that people in need get the drug, copay support without regard to what drug they actually choose or their doctors choose. And one of the things that we've come up with is sort of a standard thing that's done that we all have seen this in our charitable philanthropic efforts, we're considering a matching program where Regeneron would put up and say we'll put up X dollars to some amount and that people depending upon other people putting up, we would match their contributions.

因此，我們正在嘗試找到一種方法，讓其他人和再生元公司能夠確保有需要的人能夠獲得藥物和共同支付支持，而不管他們實際選擇什麼藥物或他們的醫生選擇什麼藥物。我們想出的辦法之一是一種標準做法，我們都在慈善活動中看到了這一點，我們正在考慮一個配套計劃，由再生元公司出資，並表示我們將出資 X 美元到一定數額，而那些依賴其他人出資的人，我們將匹配他們的捐款。

We would hope that this might stimulate others to be more philanthropic than they've been. We are working through the mechanics of this with the foundation. When this all can get launched, we hope in the not too distant future.

我們希望這可以激勵其他人比以前更加熱衷於慈善。我們正在與基金會合作研究這個機制。我們希望在不久的將來這一切都能夠啟動。

Whether or not others will step up to the plate, I'm not sure, but we certainly hope because patients do need this. I hope that that answers your question. And since this is such an important issue, because if I haven't answered it, we'll give you another question to drill down on this a little further.

我不確定其他人是否會採取同樣的行動，但我們當然希望如此，因為患者確實需要這樣做。我希望這能回答你的問題。由於這是一個非常重要的問題，如果我還沒有回答，我們會給你另一個問題來進一步深入探討這個問題。

We'll move on for now. Chris, if you'd like to ask another question, please hop back in the queue. Josh, let's move to the next question, please.

我們現在繼續。克里斯，如果你想問另一個問題，請回到隊列中。喬希，請我們進入下一個問題。

Terence Flynn, Morgan Stanley.

摩根士丹利的特倫斯弗林。

Just wanted to ask an additional one on the prefilled syringe. Len, thanks for all the details. But can you confirm that this component is something that's used in your prefilled syringe that's already approved in Europe, or is this a different component or is the component used in any other prefilled syringes?

我只是想再問一個有關預充式註射器的問題。Len，謝謝你提供的所有詳細資訊。但是您能否確認該組件是已在歐洲批准的預充式註射器中使用的組件，或者這是不同的組件，還是其他預充式註射器中使用的組件？

Just trying to understand the novelty here and why this might be a hang up.

只是想了解這裡的新穎之處以及為什麼這可能是一個障礙。

Yes, this is the same device, same design, and the same components that was approved in Europe last year and has been safely used for months. So we don't think there's any issue whatsoever with the approvability of this.

是的，這是相同的設備，相同的設計和相同的組件，去年在歐洲獲得批准，並且已經安全使用了數月。因此我們認為此事的可批准性沒有任何問題。

But the FDA has their own set of questions. They want to know did you do this or where's the data for that and that sort of thing. And they don't just automatically approve it just because Europe has approved it. But yes, your question is a good one, Terence.

但 FDA 也有自己的一連串問題。他們想知道你是否做過這件事或這件事的數據在哪裡等等。他們不會因為歐洲批准了就自動批准。但是的，你的問題很好，特倫斯。

It gives us all some confidence that these issues should be resolvable because they were resolved for European approval.

這讓我們所有人都有信心，這些問題是可以解決的，因為它們是經過歐洲批准的。

Let's move to the next question, please.

請讓我們進入下一個問題。

Akash Tewari, Jefferies.

Akash Tewari，傑富瑞。

So you mentioned $400 million in patient assistance to Good Days. Can you comment on what percent of your US patient base receives funding in 2024? Is 25% a fair estimate? And just to kind of drill into the specifics, from what you've seen in Q1, what percentage of those patients are dual covered or have supplemental insurance so they would be able to get back onto EYLEA without help from Good Days?

您提到向 Good Days 提供 4 億美元的患者援助。您能否評論一下到 2024 年有多少比例的美國患者能夠獲得資助？25% 是合理的估計嗎？為了深入了解具體情況，從您在第一季看到的情況來看，有多少比例的患者擁有雙重保險或補充保險，因此他們能夠在沒有 Good Days 幫助的情況下重新加入 EYLEA？

And then Len, assuming that other -- Roche and some of these other players don't -- aren't receptive to this matching program, what are you -- what is your team going to do, right? Is there a situation where funding to Good Days doesn't return at any point in 2025?

然後 Len，假設其他人——Roche 和其他一些球員——不接受這個匹配計劃，你——你的球隊會怎麼做，對嗎？是否存在 Good Days 的資金在 2025 年的某個時候無法恢復的情況？

A lot of questions embedded in there, but the first series of questions, we can't answer. We don't do any correlations about our contributions and the implications for EYLEA usage. That's not permitted. It's not appropriate and the people who make the decisions at Regeneron on are not the commercial people.

這其中隱藏著很多問題，但第一連串問題我們無法回答。我們沒有對我們的貢獻和對 EYLEA 使用的影響進行任何關聯。這是不允許的。這是不合適的，而且再生元的決策者不是商業人士。

This is not a conduit of any shape, matter or form, and that's not permissible under the rules. So we don't -- we can't answer any of those questions about EYLEA . In terms of what our game plan is, well, I think you've heard it.

這不是任何形狀、物質或形式的管道，並且根據規則這是不允許的。所以我們無法回答有關 EYLEA 的任何問題。關於我們的比賽計劃，嗯，我想你已經聽說了。

We want to stimulate a community of givers. You mentioned one. It doesn't have to be. It could be somebody else. If Elon Musk wants to give, that's good by us too. We're not targeting anybody in particular. We're just saying that we would like to stimulate others, and I should just leave it at that.

我們希望激發一個奉獻者社區。你提到了一個。不一定非得這樣。也可能是其他人。如果伊隆馬斯克願意捐贈，我們也很樂意。我們並不是針對任何特定的人。我們只是說我們想激勵其他人，我就不多說了。

Let's move to the next question, please.

請讓我們進入下一個問題。

Carter Gould, Cantor.

卡特·古爾德，領唱者。

Sorry to come back to the regulatory operations, and I appreciate all the color and nuance on the prefilled syringe. But Len, this is your fourth CRL and as well as a delay in the past sort of 12 months. Is there acknowledgement this performance is unsatisfactory across the regulatory group? And maybe you could highlight any steps you've taken to improve regulatory performance?

很抱歉再次回到監管操作，我很欣賞預充式註射器上的所有顏色和細微差別。但是 Len，這是您的第四次 CRL，並且在過去 12 個月內已經延遲了。監管機構是否承認這項表現並不令人滿意？也許您可以強調一下您為提高監管績效所採取的任何措施？

I recognize their idiosyncrasies. And if I'm being a fair, please correct me, but the rate of CRLs and delays really stands out versus peers.

我認清他們的特質。如果我是公平的，請糾正我，但與同行相比，CRL 和延遲率確實很突出。

Well, that's a tough one. Well, if anybody's going to take responsibility, it's going to be me. I'm not putting this on a regulatory group whatsoever because I think they've done a spectacular job as a manufacturing group. We have a lot of activity at the FDA. I can't remember what we said, nine submissions and we -- so we're going to have more than our share of regulatory interactions.

嗯，這是一個棘手的問題。好吧，如果有人要承擔責任的話，那就是我。我不會把這歸咎於監管部門，因為我認為他們作為製造業部門已經做得非常出色了。我們在 FDA 有很多活動。我不記得我們說過什麼，九份提交，所以我們將承擔超過我們份額的監管互動。

I think our team is first-rate. The kinds of issues that have come up are reflecting, in my view, an increased scrutiny by the FDA post-COVID on contract manufacturers performing a variety of functions. All of our CRLs, -- I should say not all, but for the vast majority of our CRLs, they relate to these issues at third party suppliers which the FDA recognized were woefully behind the times during COVID.

我認為我們的團隊是一流的。在我看來，出現的這類問題反映出 FDA 在新冠疫情後對履行各種職能的合約製造商加強了審查。我們所有的 CRL——我應該說不是全部，但對於我們絕大多數的 CRL 來說，它們都與第三方供應商的這些問題有關，FDA 認識到這些問題在 COVID 期間嚴重落後於時代。

There wasn't enough of them. They were flunking inspections. And so I think the FDA is trying to step up the game if you will of these contract manufacturers. And since we're so active, we see more. I don't think it's a -- I'll acknowledge for sure that we're unhappy about this.

它們的數量不夠。他們沒有通過檢查。因此我認為 FDA 正在試圖加強這些合約製造商的監管。因為我們非常活躍，所以我們看到更多。我不認為這是——我肯定承認我們對此感到不滿。

And if there's a blame, I'm happy to take it personally. But it's certainly not the reflection on a regulatory group and/or manufacturing people who are working really hard to get this right. Now in some cases, the rules have changed sort of midgame.

如果有人指責我，我很樂意承擔責任。但這肯定不是監管機構和/或製造業人員為做好此事而付出巨大努力的反映。現在在某些情況下，規則在比賽中期已經改變了。

We had a CRL where we hadn't quite enrolled enough people. And why did the FDA change that sort of approach was because other manufacturers weren't bothering to enroll anybody over a 10 year period. And so they've said, we're not going to do these accelerated approvals.

我們有一個 CRL，但尚未招募足夠多的人。FDA 改變這種方法的原因是其他製造商在 10 年內都懶得招募任何人。所以他們說，我們不會採取這些加速審批措施。

So we got caught up in that. But we've rectified that. And we're expecting that approval to come. There was another CRL related to a manufacturing thing with -- originally with EYLEA, out of our control. We got that. I don't want this to sound like excuses.

所以我們陷入了其中。但我們已經糾正了這一點。我們期待獲得批准。還有另一個與製造相關的 CRL — — 最初與 EYLEA 有關，不受我們控制。我們明白了。我不想讓這聽起來像是藉口。

We own the issues because it's our product, but it is reflective, I think, more of what is going on at the level of the contract manufacturers.

我們負責這些問題，因為這是我們的產品，但我認為，它更反映了合約製造商層面正在發生的事情。

Let's move to the next question, please.

請讓我們進入下一個問題。

Brian Abrahams, RBC.

布萊恩·亞伯拉罕斯，RBC。

This is Joe on for Brian.

這是喬 (Joe) 取代布萊恩 (Brian)。

So for itepekimab, has there been any further evolution of our understanding in IL-33 as a therapeutic target since it's Phase 2 COPD data and the mechanistic rationale behind itepekimab's more pronounced benefit in former smokers?

那麼對於伊替派單抗，自從獲得 2 期 COPD 數據以及伊替派單抗對戒菸者有更顯著益處的機制原理以來，我們對 IL-33 作為治療靶點的理解是否有了進一步的發展？

And as you expand itepekimab development, how will the COPD results guide the further expansion?

隨著 itepekimab 開發的擴大，COPD 結果將如何指導進一步的擴展？

Well, a lot of our insights into IL-33 come from genetics in the pathway. As you know, from our Regeneron Genetics Center, we have a large number of human sequence. We can actually see variation in the IL-33 pathway.

嗯，我們對 IL-33 的許多見解都來自於該通路的遺傳學。如您所知，我們從再生元遺傳學中心獲得了大量的人類序列。我們實際上可以看到 IL-33 路徑的變化。

And what we actually see is that patients who are genetically deficient in this pathway are protected from COPD and those who have excess IL-33 activity are more prone to COPD as well as a series of other diseases, some of which we've described we're investigating with additional clinical trials.

我們實際上看到的是，基因上缺乏這種途徑的患者不會患上 COPD，而 IL-33 活性過高的患者更容易患上 COPD 以及一系列其他疾病，其中一些我們已經描述過，我們正在通過額外的臨床試驗進行研究。

So that's where the whole rationale and the whole idea comes from which indications we go after. As we've already said, our Phase 2 study showed an overall reduction in exacerbations that was driven by this former smoker population.

這就是我們所追求的整個原理和整個想法的來源。正如我們已經說過的，我們的第二階段研究表明，這群曾經吸煙的人引起的病情惡化總體上有所減少。

We think we might be understanding a little bit about that mechanism, but nothing definitive and new up until this point. And I do remind you that these Phase 3 studies did pass an interim analysis about halfway through the program, which gives us additional hope and confidence.

我們認為我們可能對該機制有所了解，但到目前為止還沒有任何明確的新見解。我確實提醒您，這些第三階段研究確實在專案進行到一半時通過了中期分析，這給了我們額外的希望和信心。

So the genetics is strong here. The Phase 2 data was strong here. And the fact that we passed an interim efficacy barrier gives us confidence here. But obviously, we'll be getting the data in a short period of time, and that will be definitive.

所以這裡的遺傳基因很強。第二階段的數據表現強勁。而且，我們通過了暫時的功效障礙這一事實給了我們信心。但顯然，我們將在短時間內獲得數據，而且數據將是確定的。

Any thoughts on future indications based on the COPD results?

根據 COPD 結果對未來適應症有何想法？

Well, we announced, as I just described in my comments, a few ongoing studies and a few studies that we're initiating. We're also very excited about the opportunity in asthma because the data is very strong there. And I think that depending on the COPD results, we might be considering moving into that space as well because the genetics there is also very, very strong.

嗯，正如我剛才在評論中所描述的，我們宣布了一些正在進行的研究和一些我們正在啟動的研究。我們對氣喘領域的治療機會也感到非常興奮，因為該領域的數據非常強勁。我認為，根據 COPD 的結果，我們可能也會考慮進入該領域，因為那裡的遺傳學也非常非常強。

Let's move to the next question, please.

請讓我們進入下一個問題。

William Pickering, Bernstein.

威廉‧皮克林，伯恩斯坦。

On the EYLEA HD monthly dosing submission, the [LRR] safety trial just completed enrolling in March, and I believe that you submitted the filing before that. So what percent of the total enrollment was included in the submission?

關於 EYLEA HD 每月劑量提交，[LRR] 安全試驗剛剛在 3 月完成招募，我相信您在此之前就提交了文件。那麼，提交的申請佔總入學人數的百分之多少？

Did you have alignment with the FDA? This would be sufficient? And what's your overall level of confidence in this submission at this point?

您是否與 FDA 達成了一致？這樣就夠了嗎？目前，您對這份提交的整體信心程度如何？

I don't think we're going to get into the details of all of that. Suffice to say that they've accepted our submission and therefore, there's no deficiency, say like we didn't have enough numbers or something like that.

我認為我們不會深入討論所有這些細節。可以說，他們已經接受了我們的提交，因此不存在任何缺陷，例如我們的數量不夠或諸如此類的情況。

Now it's a review issue. And we'll see how that process goes. And we'll let you know when we know something. But in terms of whether or not we've satisfied the requirement for evaluation, we did pass that hurdle because it was accepted for review.

現在這是一個審查問題。我們將觀察這一進程如何進行。一旦我們知道了什麼，我們就會通知你。但就我們是否滿足評估要求而言，我們確實跨越了那道障礙，因為它已被接受審查。

Let's move to the next question.

我們來討論下一個問題。

Evan Seigerman, BMO Capital Markets.

埃文·塞格曼 (Evan Seigerman)，BMO 資本市場。

I want to pose one for you, Len. Hypothetically speaking, if you could redesign a way to provide patient assistance without the use of charities and current legislation aside, how would you structure that program for Medicare?

我想為你擺一個姿勢，Len。假設一下，如果您可以重新設計一種在不使用慈善機構和現行立法的情況下提供患者援助的方式，那麼您將如何建立醫療保險計劃？

Would it be direct kind of co-payments for patients who need it or other kind of mechanisms? How do you think about that?

對於有需要的患者來說，這是否是直接的共同支付方式，還是其他類型的機制？您對此有何看法？

Yeah. That is a great question, and I addressed that, I think, recently on a CNBC interview that I gave. But let me revisit it. Just to level set everybody, remember the point being is that we cannot do direct patient assistance to people who are having their drugs paid for by government funding.

是的。這是一個很好的問題，我想我最近在接受 CNBC 採訪時已經回答過這個問題。但請讓我重新回顧一下。只是為了讓每個人都公平起見，請記住，我們不能直接為那些由政府資助支付藥費的患者提供患者援助。

I suggested with the stroke of a Presidential pen that they could choose to allow sponsors to provide copay assistance directly the way we do for commercial patients. The notion that somebody is going to take an expensive drug that requires treatment for cancer, let's say, or an injection in the eye or something like that because they get copay assistance seems to me ill-founded.

我以總統的筆跡建議，他們可以選擇允許贊助商直接提供共付額援助，就像我們為商業患者提供的那樣。有人因為獲得了共同支付援助而願意服用治療癌症所需的昂貴藥物，或註射眼部藥物或類似藥物，這種想法在我看來是沒有根據的。

And maybe it might increase utilization perhaps. But far more importantly, it means patients will get the best drug that they and their doctors choose for them. There is lots of evidence. And we just had it this quarter that we -- most retinal specialists will tell you that Avastin is not the best drug to treat patients with a variety of retinal diseases, yet people who are poor, who can't afford copays wind up getting that in a disproportionate number as you saw when there was no copay assistance here.

也許它可能會提高利用率。但更重要的是，這意味著患者將獲得他們和醫生為他們選擇的最佳藥物。有很多證據。我們本季剛剛了解到，大多數視網膜專家會告訴您，Avastin 不是治療各種視網膜疾病患者的最佳藥物，但正如您在沒有共付額援助時看到的那樣，貧困人口、無力承擔共付額的人最終會以不成比例的數量接受這種治療。

And that's really the wrong that needs to be righted. And were I designing this, I would allow copay assistance by directly from sponsors to patients. I think one could literally do this. If the President wanted to do this, he would get millions and millions of seniors would be greatly appreciative that they weren't fussing and worrying and figuring out, well, am I getting the best treatment that's going to make me not lose my vision or am I getting the right cancer treatment so that I can live to see the next year and so forth.

這確實是需要糾正的錯誤。如果我設計這個，我會允許贊助商直接向患者提供共同支付援助。我認為人們確實可以做到這一點。如果總統願意這樣做，數以百萬計的老年人將會非常感激，因為他們不用再煩惱、擔心，也不用再糾結，我是否得到了最好的治療，讓我不會失去視力，或者我是否得到了正確的癌症治療，讓我可以活到明年等等。

I think that that would be a great thing for the President to do.

我認為這對總統來說是一件偉大的事。

Let's move to one more -- next question, please.

讓我們再討論一個問題──請問下一個問題。

Salveen Richter, Goldman Sachs.

薩爾文·里克特，高盛。

You tightened your capital expenditure guidance for this year. Can you help us understand this in the context of your recent manufacturing announcements and cadence here for forward spend noting the current environment?

您收緊了今年的資本支出指引。您能否根據您最近的製造公告和當前環境下的未來支出節奏來幫助我們理解這一點？

Yeah. Thanks, Salveen for the question.

是的。謝謝 Salveen 提出這個問題。

We lowered the top end of the range by $25 million. There's nothing really to look through that other than just some timing of the way we see the expenditures going out. But we're committed to our capital plans and nothing has changed accordingly.

我們將最高價格範圍降低了 2500 萬美元。除了我們看到支出支出的時間安排之外，實際上沒有什麼可以看透的。但我們致力於我們的資本計劃，因此一切都沒有改變。

I think we have time for one more question.

我想我們還有時間再回答一個問題。

David Risinger, Leerink Partners.

Leerink Partners 的 David Risinger。

Well, I'm hoping you can address a big picture question. The industry is facing three major US government risks, specifically actions that are harming biopharma innovation, including FDA disruption, questioning of proven medical science, evisceration of the NIH, in addition, tariff threats, and then finally, the Trump administration's agenda to take down drug prices more than the Biden administration.

好吧，我希望你能回答一個大問題。該行業正面臨美國政府的三大風險，具體來說，這些行動正在損害生物製藥創新，包括 FDA 的干擾、對已證實的醫學科學的質疑、對 NIH 的削弱，此外還有關稅威脅，最後是川普政府比拜登政府更大力降低藥品價格的議程。

So considering what appears to be a lack of appreciation in Washington of the benefits that the biopharmaceutical industry brings to Americans, could you please comment on how you and your executive team and Board are engaging differently today with Washington leadership to change the political agenda for the better?

因此，考慮到華盛頓似乎對生物製藥行業為美國人帶來的好處缺乏認識，您能否評論一下您和您的執行團隊和董事會今天如何以不同的方式與華盛頓領導層接觸，以改變政治議程？

Great question, David.

很好的問題，大衛。

Look, I think during this transition period, there is a lot of disruption in Washington. There is loss of personnel, reduction in force, new people in charge, new focuses, and so forth. I told the President that I thought that RFK Jr., while he thinks outside the box, needed some assistance on the science front.

聽著，我認為在這個過渡時期，華盛頓出現了很多混亂。人員流失、兵力減少、負責人上任、關注點發生變化等等。我告訴總統，我認為羅伯特甘迺迪雖然思考方式很獨特，但在科學方面仍需要一些幫助。

I said that straight out and offered to provide that. And I think that there are others who feel similarly as I do that we can't lose the ability to do science. Does that mean that the way science has been done in this country, the way grants have been given out, is done exactly right?

我直接說了這一點並願意提供這一點。我認為其他人也會和我一樣認為我們不能失去從事科學研究的能力。這是否意味著這個國家進行科學研究的方式、發放補助的方式都是完全正確的？

No, there is room for improvement across all of what we do. We saw that during COVID when one of our antibodies didn't get the kind of indication it clearly should have based on the science. Why that happened? Somebody wasn't following the science.

不，我們所做的一切都還有進步的空間。我們發現，在 COVID 期間，我們的一種抗體沒有得到科學所明確指出的那種指示。為什麼會發生這樣的事？有人沒有遵循科學。

So there's room for improvement. But of course, there's risk, David, as you pointed out. If we take a path where we just stop following science and we give up on tried and true methodologies, I think we could be in trouble.

因此還有改進的空間。但當然，正如你所指出的，大衛，這是有風險的。如果我們走上一條不再遵循科學、放棄經過驗證的方法的道路，我認為我們可能會陷入困境。

If we take a fresh look at things but still get guided by scientific principles, I think things could improve. Obviously, experience does matter, and I really hope that we do not lose really good people at the FDA in the rank and file or even at the policy level.

如果我們重新審視事物，但仍然以科學原理為指導，我認為事情會有所改善。顯然，經驗確實很重要，我真的希望我們不會在 FDA 的基層甚至政策層面失去真正優秀的人才。

I think that would be deleterious. So I think that we don't get to set the policy. We hopefully get to influence a little bit and we try and work through it. But the company spends a fair amount of effort trying to keep people on a path that will serve the health of our citizens as best it can.

我認為那將是有害的。所以我認為我們無權制定政策。我們希望能夠產生一點影響，並努力解決它。但該公司花費了相當大的努力，試圖讓人們走上一條盡可能服務公民健康的道路。

Okay. Thank you and thanks to everyone who dialed in today for your interest in Regeneron. We apologize to those remaining in the Q&A queue who we did not have a chance to hear from today. As always, the Investor Relations team is available to answer any remaining questions you may have.

好的。感謝你們，也感謝今天撥打電話關注 Regeneron 的所有人。對於那些今天沒有機會聽取我們問答意見的仍在等待隊列中的人們，我們深感抱歉。像往常一樣，投資者關係團隊可以解答您可能有的任何其他問題。

Thank you once again and have a great day.

再次感謝您並祝您有美好的一天。

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。