雷傑納榮製藥 (REGN) 2024 Q2 法說會逐字稿

Welcome to the Regeneron Pharmaceuticals second-quarter 2024 earnings conference call. My name is Shannon, and I will be your operator for today's call. (Operator Instructions) Please note that this conference call is being recorded.

歡迎參加再生元製藥 2024 年第二季財報電話會議。我叫香農，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。

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

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。

Thank you, Shannon. Good morning, good afternoon and good evening to everyone listening around the world. Thank you for your interest in Regeneron and welcome to our second quarter 2024 earnings conference call. An archive and transcript of this call will be available on the Regeneron Investor Relations website shortly after the call ends.

謝謝你，香農。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 年第二季財報電話會議。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檔案和文字記錄。

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.

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

我想提醒您，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 Regeneron 及其產品和業務、財務預測和指導、開發計劃和相關預期里程碑、合作、財務、監管事項、付款人覆蓋和報銷問題、知識產權、待定的訴訟訴訟和其他程序以及競爭。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。

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 June 30, 2024, 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.

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 6 月 30 日的季度的 10-Q 表。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。

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 Investor Relations team will be available to answer any further questions.

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。在我們的電話會議結束後，克里斯和投資者關係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 continued its track record of strong execution, highlighted by double-digit revenue and earnings growth in the second quarter along with important advances across our broad pipeline.

謝謝，瑞安。感謝大家參加今天的電話會議。再生元持續保持強勁執行力的記錄，第二季營收和獲利成長兩位數，以及我們廣泛的產品線取得重要進展。

For my remarks today, I'd like to briefly review some of the key performance drivers for the quarter and then discuss near-term pipeline opportunities. After my remarks, George will provide further updates on our pipeline. Marion will then review our commercial performance. And finally, Chris will detail our quarterly financial results and discuss updates to our full year guidance.

在今天的演講中，我想簡要回顧一下本季度的一些關鍵績效驅動因素，然後討論近期的管道機會。在我發言後，喬治將提供有關我們管道的進一步更新。然後，馬里昂將審查我們的商業表現。最後，克里斯將詳細介紹我們的季度財務業績，並討論我們全年指導的更新。

Second quarter 2024 total revenues grew 12% to $3.55 billion, primarily driven by sales of EYLEA HD in the United States. Higher Sanofi collaboration revenues reflecting the continued strong performance of Dupixent as well as robust growth for Libtayo. EYLEA HD generated $304 million in its third full quarter on the US market and continues to outperform recent launches in the anti-VEGF category. Net product sales for EYLEA HD and EYLEA combined were $1.53 billion, representing a 2.3% growth compared to the prior year.

2024 年第二季總營收成長 12%，達到 35.5 億美元，主要受到 EYLEA HD 在美國銷售的推動。賽諾菲合作收入的增加反映了 Dupixent 持續強勁的業績以及 Libtayo 的強勁成長。 EYLEA HD 在美國市場的第三個完整季度創造了 3.04 億美元的收入，並且繼續優於最近推出的抗 VEGF 類別藥物。 EYLEA HD 和 EYLEA 的產品淨銷售額合計為 15.3 億美元，比上年增長 2.3%。

We are encouraged that despite increased competition in the anti-VEGF space, we have achieved a strong EYLEA HD launch trajectory while maintaining our category-leading combined EYLEA HD and EYLEA market share of 45%. Our efforts to bring an EYLEA HD pre-filled syringe, United States market remain a high priority, and we are tracking towards a potential pre-filled syringe launch by early 2025. In summary, we continue to position EYLEA HD as the new standard-of-care for retinal diseases based on its differentiated clinical profile, coupled with strong familiarity and satisfaction among retinal specialists.

令我們感到鼓舞的是，儘管抗 VEGF 領域的競爭加劇，我們仍實現了強勁的 EYLEA HD 上市軌跡，同時保持了我們類別領先的 EYLEA HD 和 EYLEA 市場份額 45%。我們努力在美國市場推出 EYLEA HD 預充式註射器，這仍然是我們的首要任務，我們正在追蹤可能在 2025 年初推出的預充式註射器。化的臨床特徵以及視網膜專家的強烈熟悉度和滿意度，對視網膜疾病進行非護理。

Dupixent global revenues grew 29% on a constant currency basis to $3.56 billion, reflecting strong growth across all approved indications, age groups, and geographies. In June, the European Commission approved Dupixent for COPD in patients with raised blood eosinophils, marking the first global regulatory approval for Dupixent in COPD. This approval enables Dupixent to address the approximately 220,000 eosinophilic COPD patients in the EU that are currently uncontrolled on maximum and eligible therapy. The approval also represents the first biologic approved to treat this disease.

以固定匯率計算，Dupixent 全球營收成長 29%，達到 35.6 億美元，反映出所有核准的適應症、年齡層和地區的強勁成長。 6 月，歐盟委員會批准 Dupixent 用於治療血液嗜酸性粒細胞升高的慢性阻塞性肺病 (COPD) 患者，這標誌著全球監管機構首次批准 Dupixent 用於治療慢性阻塞性肺病 (COPD)。這項批准使 Dupixent 能夠解決歐盟約 22 萬名嗜酸性細胞性慢性阻塞性肺病患者的問題，這些患者目前在最大和合格的治療中仍無法得到控制。該批准也是第一個被批准用於治療這種疾病的生物製劑。

We continue to work with the FDA regarding its ongoing review for this indication and expect their decision by the September 27 PDUFA date. We and our partner, Sanofi, are prepared for US launch that many pulmonologists, respiratory key opinion leaders, and their patients have been eagerly anticipating. There is a high unmet need in COPD with Type 2 inflammation with approximately 300,000 eligible patients in the United States, and our potential launch represents a significant driver for Dupixent's continued growth.

我們將繼續與 FDA 就該適應症的持續審查進行合作，並預計他們會在 9 月 27 日 PDUFA 日期之前做出決定。我們和我們的合作夥伴賽諾菲已準備好在美國推出，許多肺科醫生、呼吸系統關鍵意見領袖及其患者一直熱切期待。美國約有 30 萬名符合條件的患者，患有 2 型發炎的慢性阻塞性肺病 (COPD) 的需求尚未得到滿足，我們的潛在推出是 Dupixent 持續增長的重要推動力。

Libtayo global net product sales were $297 million in the second quarter, an increase of 43% on a constant currency basis. Despite intense competition, Libtayo has maintained its leadership position in non-melanoma skin cancers, while making impressive inroads in non-small cell lung cancer. We are also pleased with the progress we have made in establishing an international commercial footprint to support Libtayo and other future products following our purchase of full global rights to Libtayo from Sanofi in mid-2022.

Libtayo第二季全球產品淨銷售額為2.97億美元，以固定匯率計算成長43%。儘管競爭激烈，Libtayo 仍保持其在非黑色素瘤皮膚癌領域的領導地位，同時在非小細胞肺癌領域取得了令人印象深刻的進展。繼我們於 2022 年中期從賽諾菲購買 Libtayo 的全部全球權利後，我們在建立國際商業足跡以支持 Libtayo 和其他未來產品方面取得了進展，對此我們也感到很高興。

Regarding linvoseltamab or BCMA by CD3 bispecific for relapsed refractory multiple myeloma. During its review of the linvoseltamab BLA, the FDA informed us that the third-party fill-finish manufacturer for linvoseltamab had unresolved findings from a pre-approval inspection for another company's product candidate.

關於 linvoseltamab 或 BCMA CD3 雙特異性治療復發難治性多發性骨髓瘤。在對 linvoseltamab BLA 進行審查期間，FDA 告知我們，linvoseltamab 的第三方填充製造商在對另一家公司的候選產品進行批准前檢查時發現了未解決的問題。

While we now believe these findings have been resolved, a reinspection will be required. And therefore, we anticipate any potential FDA approval for linvoseltamab is likely to be delayed beyond the August 22 PDUFA date. The FDA has not informed us of any approvability issues for linvoseltamab related to safety, efficacy, or the status of our ongoing confirmatory trial. More broadly on our pipeline, we are excited about several upcoming readouts later this year or in 2025 to further inform programs that could support significant long-term growth opportunities which George will discuss in a moment.

雖然我們現在相信這些發現已經解決，但仍需要重新檢查。因此，我們預計 FDA 對 linvoseltamab 的任何潛在批准可能會推遲到 8 月 22 日 PDUFA 日期之後。 FDA 尚未通知我們任何與安全性、有效性或我們正在進行的驗證性試驗狀態相關的 linvoseltamab 的批准問題。更廣泛地說，在我們的管道中，我們對今年晚些時候或2025 年即將發布的幾份報告感到興奮，這些報告將進一步為可能支持重大長期增長機會的計劃提供信息，喬治稍後將討論這些計劃。

In closing, our pipeline continues to generate innovative and differentiated opportunities and now has over 35 programs in clinical development spanning several distinct therapeutic areas. Our commercial team is executing well with our in-market products and is building momentum in competitive categories. Finally, we continue to prudently deploy capital with the goal of delivering long-term value to shareholders.

最後，我們的產品線繼續創造創新和差異化的機會，目前擁有超過 35 個臨床開發項目，跨越多個不同的治療領域。我們的商業團隊在市場產品方面表現良好，並在競爭類別中建立勢頭。最後，我們持續審慎配置資本，以期為股東創造長期價值。

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

這樣，我就把電話轉給喬治。

Thank you, Len. Starting with Dupixent. Regarding COPD, data from our second confirmatory trial, NOTUS, was featured as a late-breaking presentation at the American Thoracic Society Conference and simultaneously published in the New England Journal of Medicine.

謝謝你，萊恩。從 Dupixent 開始。關於慢性阻塞性肺病，我們的第二項驗證性試驗 NOTUS 的數據在美國胸腔科學會會議上作為最新報告發表，並同時發表在《新英格蘭醫學雜誌》上。

In NOTUS, Dupixent reduced exacerbations by 34% while significantly improving lung function, confirming the unprecedented results from the previously reported Phase III BOREAS trial. Based on data from NOTUS and BOREAS, Dupixent was recently approved by the European regulatory authorities for eosinophilic COPD patients uncontrolled on maximum standard-of-care inhaled therapy. Additional submissions are under review with other regulatory authorities around the world, including in the US, China, and Japan.

在 NOTUS 中，Dupixent 將病情加重減少了 34%，同時顯著改善了肺功能，證實了先前報告的 III 期 BOREAS 試驗中前所未有的結果。根據 NOTUS 和 BOREAS 的數據，Dupixent 最近獲得歐洲監管機構批准，用於治療經最高標準護理吸入治療未控制的嗜酸性細胞性慢性阻塞性肺病患者。其他提交的資料正在接受世界各地其他監管機構的審查，包括美國、中國和日本。

Beyond COPD, later this year, we are looking forward to data readouts from Phase III studies of Dupixent in chronic spontaneous urticaria and bullous pemphigoid. Seven years, after its initial FDA approval and with approval in seven different indications around the world, Dupixent continues to deliver potential new approvals for additional important disease indications. Regarding our small pilot study to potentially eliminate severe food allergies using our innovative approach that combines Dupixent and linvoseltamab or BCMA by CD3 bispecific, we continue to expect to see initial data by the end of this year.

除了 COPD 之外，今年晚些時候，我們期待 Dupixent 治療慢性自發性蕁麻疹和大皰性類天皰瘡的 III 期研究的數據讀出。七年後，Dupixent 首次獲得 FDA 批准並在全球七種不同適應症中獲得批准，並繼續為其他重要疾病適應症提供潛在的新批准。關於我們使用 Dupixent 和 linvoseltamab 或 CD3 雙特異性結合 BCMA 的創新方法潛在消除嚴重食物過敏的小型試驗研究，我們繼續期望在今年年底看到初步數據。

On itepekimab, our IL-33 antibody in development for certain COPD patients, our two Phase III studies are now fully enrolled. Study readouts and regulatory submissions for our second therapeutic candidate for this devastating disease are expected in the second half of next year.

關於 itepekimab（我們正在為某些 COPD 患者開發 IL-33 抗體），我們的兩項 III 期研究現已全部入組。我們針對這種毀滅性疾病的第二種治療候選藥物的研究結果和監管提交預計將於明年下半年公佈。

Moving to oncology and starting with fianlimab. Our LAG-3 antibody in combination with Libtayo, at the upcoming ESMO meeting in September, we look forward to presenting longer-term follow-up on the metastatic melanoma cohorts from our first-in-human study. Responses have continued to deepen with the proportion of complete responders and median progression-free survival continuing to improve.

轉向腫瘤學並從 fianlimab 開始。我們的 LAG-3 抗體與 Libtayo 結合，在即將於 9 月舉行的 ESMO 會議上，我們期待展示我們首次人體研究中轉移性黑色素瘤隊列的長期追蹤結果。隨著完全緩解者比例和中位無惡化存活期持續改善，緩解持續加深。

These results strengthen our view that fianlimab and Libtayo may be the most promising immunotherapy combination in clinical development. As we recently announced, we are looking forward to the Phase III readout in this melanoma setting next year, which could position fianlimab and Libtayo as a new standard-of-care in melanoma and eventually potentially other cancer settings.

這些結果強化了我們的觀點，即 fianlimab 和 Libtayo 可能是臨床開發中最有前景的免疫療法組合。正如我們最近宣布的，我們期待明年在這種黑色素瘤環境中進行 III 期試驗，這可能會將 fianlimab 和 Libtayo 定位為黑色素瘤以及最終可能的其他癌症環境的新護理標準。

Additionally, we hope to gain insights into the antitumor activity of this combination in non-small cell lung cancer later this year. We are also advancing fianlimab development to earlier lines of therapy with proof-of-concepts in perioperative non-small cell lung cancer and perioperative melanoma now underway with additional indications likely to follow.

此外，我們希望在今年稍後深入了解該組合在非小細胞肺癌中的抗腫瘤活性。我們也正在將 fianlimab 的開發推進到早期療法，並針對圍手術期非小細胞肺癌和圍手術期黑色素瘤進行概念驗證，目前正在進行中，後續可能還會出現其他適應症。

On to bispecifics for solid tumors. Our costimulatory bispecific antibodies are being tested in numerous studies, including as monotherapies as well as in combination with CD3 bispecifics and with Libtayo. At the ASCO Conference, we presented results for our EGFR by CD28 bispecific in combination with Libtayo. In microsatellite stable colorectal cancer tumor historically unresponsive to immunotherapy, EGFR by CD28 in combination with Libtayo demonstrated encouraging antitumor activity, with an overall response rate of 20% in patients without liver metastases.

關於實體瘤的雙特異性。我們的共刺激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。在 ASCO 會議上，我們展示了 CD28 雙特異性藥物與 Libtayo 組合的 EGFR 結果。在歷史上對免疫療法無反應的微衛星穩定結直腸癌腫瘤中，CD28 的 EGFR 與 Libtayo 聯合顯示出令人鼓舞的抗腫瘤活性，在無肝轉移的患者中總體反應率為 20%。

Regarding safety, to-date, we have not observed severe immune-related adverse events with this agent at our recommended Phase II dose. Dose expansion cohorts testing EGFR by CD28 plus Libtayo continue to enroll in various solid tumors, including non-small cell lung cancer with or without EGFR 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 期劑量下尚未觀察到該藥物與免疫相關的嚴重不良事件。以 CD28 加 Libtayo 測試 EGFR 的劑量擴展隊列繼續招募各種實體瘤，包括有或沒有 EGFR 突變的非小細胞肺癌、微衛星穩定大腸直腸癌、頭頸癌、鱗狀細胞癌等。

On to our PSMA by CD28 costimulatory bispecific, which has already demonstrated promising activity in late-line prostate cancer when combined with Libtayo. We have now initiated combination treatment of our PSMA by CD28 costim bispecific with our PSMA by CD3 bispecific, which based on preclinical studies may maintain the efficacy of served with the Libtayo combination that may improve the safety and tolerability profile. We are also testing PSMA by CD28 in other cancers.

關於我們的 CD28 共刺激雙特異性 PSMA，它與 Libtayo 聯合使用時已經在晚期前列腺癌中表現出有希望的活性。我們現在已經開始對 CD28 costim 雙特異性藥物的 PSMA 與 CD3 雙特異性藥物的 PSMA 進行聯合治療，基於臨床前研究，該治療可能會保持與 Libtayo 組合的療效，從而提高安全性和耐受性。我們也在其他癌症中透過 CD28 測試 PSMA。

Next to our bispecifics for hematology oncology. The linvoseltamab or BCMA by CD3 bispecific, an oral presentation at the European Hematologic Association Conference, we presented updated pivotal data, which continue to demonstrate a potentially best-in-class profile in late-line myeloma in terms of efficacy, safety, dosing, as well as hospitalization burden.

接下來是我們用於血液腫瘤學的雙特異性藥物。 CD3 雙特異性的 linvoseltamab 或 BCMA 在歐洲血液學協會會議上進行了口頭報告，我們提供了更新的關鍵數據，這些數據繼續證明了晚期骨髓瘤在功效、安全性、劑量、還有住院負擔。

As we expected, responses continue to deepen with longer follow-up. At 14-month median follow-up of 117 patients, 50% achieved a complete response or better with an objective overall response rate of 71%. Additional studies of linvoseltamab are now also underway in earlier stages of myeloma and in precursor conditions such as smoldering myeloma and monoclonal gammopathy of unknown significance or MGUS. Developing linvoseltamab in earlier-line myeloma settings presents an important opportunity for us to help patients and their physicians in these diseases, which currently have complex in treatment paradigms.

正如我們預期的那樣，隨著隨訪時間的延長，反應繼續加深。在對 117 名患者進行 14 個月中位數追蹤時，50% 的患者達到完全緩解或更好，客觀整體緩解率為 71%。目前也在骨髓瘤的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）中進行林沃塞他單抗的其他研究。在早期骨髓瘤環境中開發林沃司他單抗為我們提供了一個重要的機會，可以幫助患者及其醫生治療這些疾病，目前這些疾病的治療模式很複雜。

Touching on our non-oncology hematology pipeline. As highlighted previously, later this year, we are anticipating proof-of-concept results for our two Factor XI antibodies in the setting of prevention of venous thromboembolism after knee replacement surgery. The study for the antibody targeting the Factor XI A2 domain is now fully enrolled, and we expect to present results at a medical meeting in the second half of this year.

談到我們的非腫瘤血液學管道。正如之前所強調的，今年晚些時候，我們預計我們的兩種因子 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結果。針對因子 XI A2 結構域的抗體研究現已全面入組，我們預計將在今年下半年的醫學會議上發表結果。

Interim Phase II results for our second Factor XI antibody, which targets the catalytic domain, are expected by the end of this year for internal analysis. We have also started an additional proof-of-concept study to further evaluate the two antibodies profile for thrombosis prevention in patients who have a peripherally inserted catheter. Results of these studies will inform whether to proceed to registrational studies with one or both of these antibodies by next year.

我們的第二個因子 XI 抗體（針對催化結構域）的中期 II 期結果預計將於今年年底得出，以進行內部分析。我們也啟動了一項額外的概念驗證研究，以進一步評估這兩種抗體對於週邊插入導管患者預防血栓形成的作用。這些研究的結果將決定是否在明年之前對其中一種或兩種抗體進行註冊研究。

Moving to obesity. Our most advanced approach is designed to address the potential negative consequences of widespread use of GLP and GIP receptor agonists. As 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 older obese patients.

轉向肥胖。我們最先進的方法旨在解決廣泛使用 GLP 和 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可能導致肌肉大量損失，這尤其涉及老年肥胖患者。

Our myostatin antibody when combined with semaglutide with or without our active NA antibody may protect against this muscle loss as previously demonstrated in non-human primates. Part A of our COURAGE Phase II study testing a higher dose of trevogrumab or myostatin antibody in healthy subjects has now been successfully completed with no new safety signals identified. Part B of the study, which evaluates our muscle preservation antibodies in combination with semaglutide and obese participants has started enrolling patients. Assuming a reasonable pace of enrollment, we continue to expect to report top-line results, including changes in body weight, fat mass and muscle mass by the second half of 2025.

我們的肌肉生長抑制素抗體與索馬魯肽（無論有或沒有我們的活性 NA 抗體）聯合使用，可以防止這種肌肉損失，正如之前在非人靈長類動物中所證明的那樣。我們的 COURAGE II 期研究的 A 部分在健康受試者中測試了更高劑量的 trevogrumab 或肌肉生長抑制素抗體，現已成功完成，沒有發現新的安全信號。研究的 B 部分評估了我們的肌肉保存抗體與索馬魯肽和肥胖參與者的結合，已開始招募患者。假設入學速度合理，我們繼續期望在 2025 年下半年之前報告主要結果，包括體重、脂肪量和肌肉量的變化。

I will conclude with our genetics medicines efforts. At the ASGCT Conference, we presented updated data from our DB-OTO gene therapy program for genetic hearing loss due to mutations of the otoferlin gene. The first child treated with this therapy, an 11-month-old girl who is profoundly deaf at baseline, had hearing in the normal range by 24 weeks after treatment. Also, initial hearing improvements were observed in a second child, dose at 4 years of age, at a 6-week assessment with additional follow-up plan.

我將以我們在遺傳藥物方面的努力作為結束語。在 ASGCT 會議上，我們展示了 DB-OTO 基因治療計劃的最新數據，該計劃用於治療因 otoferlin 基因突變導致的遺傳性聽力損失。第一個接受這種療法治療的兒童是一名 11 個月大的女孩，她在基線時患有嚴重耳聾，但在治療後 24 週時聽力恢復到正常範圍。此外，在為期 6 週的評估和額外的後續計劃中，在 4 歲時服用的第二個孩子中觀察到了初步聽力改善。

As of July, we have dosed five patients in our study, and we are on track to enroll several more patients this year. We also look forward to bringing additional otoferlin gene therapy programs to the clinic in the coming years with the potential to address more common forms of monogenic hearing loss. Regarding our Intellia collaboration in transthyretin amyloidosis with cardiomyopathy, the world's first Phase III program for in vivo CRISPR-based therapy is enrolling at a rapid pace, indicating considerable interest from investigators and patients.

截至 7 月，我們的研究已對 5 名患者進行了給藥，今年我們預計將招募更多患者。我們也期待在未來幾年將更多的 otoferlin 基因治療計畫引入臨床，有可能解決更常見形式的單基因聽力損失。關於我們在轉甲狀腺素蛋白澱粉樣變性心肌病變方面的 Intellia 合作，世界上第一個基於 CRISPR 的體內治療的 III 期計畫正在快速招募，這表明研究人員和患者相當感興趣。

In addition, we are also on track to be the first to use of CRISPR technology to insert a corrective gene in vivo for a deficiency disease, hemophilia B. As noted previously, we have enrolled initial patients in the leading portion of this trial, and first patient should be dosed soon. Our siRNA collaboration with Alnylam has not only demonstrated successful silencing of genes in the liver but also for the first time for siRNA in the brain. This opens up opportunities for us to go after other disease-causing genes in the brain.

此外，我們也有望成為第一個使用 CRISPR 技術在體內插入糾正基因來治療缺陷性疾病 B 型血友病的公司。第一個病人應該盡快給藥。我們與 Alnylam 的 siRNA 合作不僅證明了肝臟中基因的成功沉默，而且還首次證明了大腦中 siRNA 的成功沉默。這為我們尋找大腦中其他致病基因提供了機會。

A study of ALN-SOD in ALS patients with SOD1 mutations recently initiated. Other CNS-directed siRNA programs are expected to enter the clinic shortly, including targeting HTT for Huntington's disease, synuclein for Parkinson's and tau for Alzheimer's and other neurodegenerative diseases. Additionally, with regard to our C5 program, our innovative approach involving the first combination of an antibody together with an siRNA both targeting the same molecule is progressing well and we are expecting to present updated data for initial potential indication, paroxysmal nocturnal hemoglobinuria by the end of this year.

最近啟動了一項針對具有 SOD1 突變的 ALS 患者的 ALN-SOD 研究。其他針對中樞神經系統的 siRNA 計畫預計很快就會進入臨床，包括針對亨廷頓舞蹈症的 HTT、針對帕金森氏症的突觸核蛋白以及針對阿茲海默症和其他神經退化性疾病的 tau 蛋白。此外，關於我們的C5 項目，我們的創新方法涉及首次將抗體與siRNA 組合，兩者都靶向相同的分子，進展順利，我們期望在年底前提供初始潛在適應症（陣發性睡眠性血紅蛋白尿症）的最新數據今年的。

We're also looking forward to starting our Phase III program in geographic atrophy in the second half of this year. In summary, we continue to drive forward our innovative development pipeline and anticipate reading out several pivotal and proof-of-concept data sets over the next 12 to 18 months. Our early research efforts continue to be productive with multiple novel programs potentially advancing to the clinic over that same time frame.

我們也期待在今年下半年啟動地理萎縮的第三階段計畫。總而言之，我們將繼續推進我們的創新開發流程，並預計在未來 12 至 18 個月內讀出幾個關鍵和概念驗證資料集。我們的早期研究工作持續富有成效，多個新穎的項目有可能在同一時間範圍內推進到臨床。

And with that, I will turn the call over to Marion.

接下來，我會將電話轉給馬里昂。

Thank you, George. Our second quarter commercial results further solidify Regeneron's leadership across therapeutic categories. Our performance demonstrates the ongoing strength and diversity of our product portfolio with continued growth opportunities powered by existing and upcoming product and indication launches across multiple geographies.

謝謝你，喬治。我們第二季的商業業績進一步鞏固了再生元在治療領域的領導地位。我們的業績證明了我們產品組合的持續實力和多樣性，以及在多個地區現有和即將推出的產品和適應症的推動下的持續成長機會。

I'll start with EYLEA HD and EYLEA in the US. In the second quarter, combined net sales for both medicines grew 2.3% year-over-year to $1.53 billion. EYLEA continues its clear category leadership while EYLEA HD remained the fastest growing medicine in this highly competitive category. EYLEA HD continued its launch momentum in the second quarter, delivering net product sales of $304 million, which represents 52% sequential growth. EYLEA HD continues to be the fastest launch of any anti-VEGF therapy since EYLEA more than a decade ago and the trajectory confirms a significant transition to EYLEA HD is underway.

我將從 EYLEA HD 和美國的 EYLEA 開始。第二季度，這兩種藥物的淨銷售額合計年增 2.3%，達到 15.3 億美元。 EYLEA 繼續保持其明顯的類別領導地位，而 EYLEA HD 仍然是這個競爭激烈的類別中成長最快的藥物。 EYLEA HD 第二季持續保持推出動能，產品淨銷售額達 3.04 億美元，季增 52%。 EYLEA HD 仍然是自十多年前 EYLEA 以來推出最快的抗 VEGF 療法，其發展軌跡證實了向 EYLEA HD 的重大轉變正在進行中。

The breadth and depth of EYLEA HD prescribing continues to grow with utilization across a broad range of patients, including a treatment-naive population, which has doubled since last quarter. Physicians are also increasingly switching patients to EYLEA HD from other anti-VEGF treatments based on their positive early treatment experiences.

EYLEA HD 處方的廣度和深度隨著廣大患者的使用而不斷增長，其中包括未接受過治療的人群，該人群自上季度以來增加了一倍。基於積極的早期治療經驗，醫生也越來越多地將患者從其他抗 VEGF 治療轉為 EYLEA HD。

And these switch patients, early real-world data indicate that treatment intervals are being extended with EYLEA HD. EYLEA HD's durability, along with the same trusted efficacy, visual acuity and safety as EYLEA represents a meaningful improvement for patient lives and greater efficiency for physician practices.

對於這些轉換的患者，早期的現實數據顯示 EYLEA HD 的治療間隔正在延長。 EYLEA HD 的耐用性以及與 EYLEA 相同的值得信賴的功效、視力和安全性代表著對患者生活的有意義的改善和醫生實踐的更高效率。

The number of physician offices ordering EYLEA HD during the second quarter increased by more than 50% compared to the prior quarter. We believe this suggests prescriber confidence in EYLEA HD's clinical profile as well as in reimbursement now that the permanent J-code has been well established.

第二季訂購 EYLEA HD 的醫生診所數量比上一季增加了 50% 以上。我們相信，這表明處方者對 EYLEA HD 的臨床概況以及報銷充滿信心，因為永久 J 代碼已經得到很好的確立。

Of note, we recognize the importance of providing physicians with a pre-filled syringe option and as Len mentioned, we're excited about our anticipated EYLEA HD pre-filled syringe launch. In summary, we're pleased with our second quarter performance for EYLEA HD and EYLEA and remain on track to achieve our goal of establishing EYLEA HD as the new standard-of-care for retinal disease.

值得注意的是，我們認識到為醫生提供預填充注射器選項的重要性，正如 Len 所提到的，我們對預期的 EYLEA HD 預填充注射器的推出感到興奮。總而言之，我們對 EYLEA HD 和 EYLEA 第二季度的業績感到滿意，並將繼續實現我們將 EYLEA HD 確立為視網膜疾病新護理標準的目標。

Next to Dupixent, which delivered 29% growth in the second quarter on a constant currency basis with global net sales of $3.56 billion. We are approaching the important milestone of 1 million patients on Dupixent worldwide. In addition, there's substantial opportunity for even more patients to benefit from Dupixent based on significant unmet need across indications, ages and geographies.

其次是 Dupixent，第二季以固定匯率計算成長 29%，全球淨銷售額為 35.6 億美元。我們正在接近 Dupixent 全球患者數量達到 100 萬的重要里程碑。此外，由於跨適應症、年齡和地理區域的顯著未滿足的需求，更多患者有很大機會從 Dupixent 中受益。

In the US, net sales grew 24% to $2.61 billion, driven by an increased demand across all five approved indications. Dupixent continues its number one leadership position and new-to-brand prescriptions across all approved indications. Our commercial team remains laser-focused on pursuing initiatives that drive patient awareness and support prescribing. We continue to see increasing penetration in our blockbuster indications of atopic dermatitis, asthma and nasal polyps.

在美國，受所有五個批准適應症需求成長的推動，淨銷售額成長 24%，達到 26.1 億美元。 Dupixent 繼續保持其第一的領導地位，並在所有批准的適應症中提供新品牌處方。我們的商業團隊仍然專注於推動提高患者意識和支持處方的措施。我們持續看到異位性皮膚炎、氣喘和鼻息肉等重磅適應症的滲透率不斷提高。

Additionally, recent launches in eosinophilic esophagitis and prurigo nodularis are exceeding our expectations and new patient initiations are steadily increasing. We hear remarkable stories of patients as young as one year of age with EoE, who are now thriving on Dupixent following its approval in January of this year.

此外，最近針對嗜酸性粒細胞性食道炎和結節性癢疹的治療超出了我們的預期，並且新患者的治療正在穩步增加。我們聽到了年僅一歲的 EoE 患者的非凡故事，在今年 1 月獲得 Dupixent 批准後，他們現在在 Dupixent 上茁壯成長。

The European Commission also recently approved Dupixent in COPD patients with raised blood eosinophils with patients already getting treatment in Germany. We all recognize that there is significant unmet need worldwide among patients with this debilitating disease and Dupixent represents the first biologic medicine for COPD. Our US team is ready for the anticipated FDA approval of Dupixent in COPD by late September and estimate approximately 300,000 US patients may benefit from Dupixent in this indication separately, an FDA decision for Dupixent in adolescents with chronic rhinosinusitis and nasal polyps is expected next month.

歐盟委員會最近也批准 Dupixent 用於治療血液嗜酸性粒細胞升高的慢性阻塞性肺病患者，這些患者已經在德國接受治療。我們都認識到，全球範圍內患有這種使人衰弱的疾病的患者的需求明顯未得到滿足，而 Dupixent 代表了第一種治療慢性阻塞性肺病的生物藥物。我們的美國團隊已做好準備，預計FDA 將在9 月底批准Dupixent 治療慢性阻塞性肺病，並估計大約30 萬名美國患者可能會從Dupixent 的這一適應症中受益，FDA 預計下個月將決定將Dupixent 用於患有慢性鼻竇炎和鼻息肉的青少年。

As George mentioned, there are two Dupixent Phase III programs reading out later this year in chronic spontaneous urticaria and bullous pemphigoid. If data from these trials are positive, Dupixent has the potential to support even more patients with unmet need. We also made significant progress with Libtayo in the second quarter with global net sales of $297 million, up 43% year-over-year on a constant currency basis. Strong commercial execution resulted in market share gains across both skin and lung cancers.

正如 George 所提到的，今年晚些時候，有兩個 Dupixent III 期計畫將在慢性自發性蕁麻疹和大皰性類天皰瘡方面公佈。如果這些試驗的數據是正面的，Dupixent 有潛力為更多需求未滿足的患者提供支援。第二季度，我們與 Libtayo 的合作也取得了重大進展，全球淨銷售額達到 2.97 億美元，以固定匯率計算年增 43%。強大的商業執行力導致皮膚癌和肺癌的市場份額增加。

In the US, net sales grew 40% to $182 million with growth across all market segments and indications. In non-melanoma skin cancer, we continue to extend Libtayo leadership with increasing demand and market share. In lung cancer, Libtayo is recognized by physicians as an important therapy for their lung cancer patients and continues to gradually gain market share. Outside the US, our teams are delivering excellent results with net product sales of $115 million as Regeneron continues its international expansion. Libtayo net product sales in some of these international markets were favorably impacted by approximately $15 million of stocking purchases.

在美國，隨著所有細分市場和適應症的成長，淨銷售額成長了 40%，達到 1.82 億美元。在非黑色素瘤皮膚癌領域，隨著需求和市場份額的增加，我們繼續擴大 Libtayo 的領導地位。在肺癌方面，Libtayo被醫生認為是肺癌患者的重要治療方法，並繼續逐步獲得市場份額。在美國以外，隨著 Regeneron 繼續進行國際擴張，我們的團隊取得了出色的業績，產品淨銷售額達到 1.15 億美元。 Libtayo 在其中一些國際市場的淨產品銷售額受到約 1500 萬美元的庫存採購的有利影響。

Our oncology team is also eagerly awaiting the potential FDA and EU decisions for linvoseltamab in late-stage myeloma. We believe linvoseltamab represents a best-in-class opportunity and we look forward to potential launch. In summary, our commercial team continues to deliver on our goal to provide Regeneron medicines to even more patients worldwide. There is meaningful future growth potential within our approved indications and our robust pipeline provides both near and long-term opportunities to advance patient care.

我們的腫瘤學團隊也熱切等待 FDA 和歐盟對林沃司他單抗治療晚期骨髓瘤的潛在決定。我們相信 linvoseltamab 代表了一流的機會，我們期待潛在的推出。總之，我們的商業團隊將繼續實現我們的目標，為全球更多患者提供再生元藥物。我們批准的適應症具有有意義的未來成長潛力，我們強大的產品線為推進患者護理提供了近期和長期的機會。

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

這樣，我會將電話轉給克里斯。

Thank you, Marion. My comments today on Regeneron's financial results and outlook will be on a non-GAAP basis unless otherwise noted. Regeneron delivered strong double-digit top and bottom-line growth in the second quarter.

謝謝你，馬里昂。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。再生元在第二季度實現了兩位數的營收和淨利潤強勁增長。

Total revenues increased 12% year-over-year to $3.5 billion, primarily driven by strong execution of the ongoing EYLEA HD launch in the US, higher Sanofi collaboration revenue and continued global sales growth from Libtayo. Second quarter diluted net income per share grew 13% from the prior year to $11.56 on net income of $1.4 billion. Second quarter revenues from our Sanofi collaboration grew to $1.1 billion, primarily composed of our share of collaboration profits of $988 million, which increased by 32% compared to the prior year driven by Dupixent's continued volume growth and improving margins.

總營收年增 12%，達到 35 億美元，這主要是由於 EYLEA HD 在美國推出的強勁執行力、賽諾菲合作收入的增加以及 Libtayo 的全球銷售持續成長。第二季攤薄後每股淨利較上年同期成長 13%，達到 11.56 美元，淨利為 14 億美元。第二季我們與賽諾菲合作的營收成長至11 億美元，主要由我們分享的9.88 億美元合作利潤組成，在Dupixent 銷量持續成長和利潤率提高的推動下，該利潤比上年增長了32 %。

Reimbursement from manufacturing and commercial supply, the other component of Sanofi collaboration revenue was $157 million, taking into account increased volumes, offset by manufacturing efficiencies, we continue to expect reimbursement for manufacturing and commercial supply in 2024 to be comparable to 2023 on a full year basis. The Sanofi development balance was approximately $2 billion at the end of the second quarter, reflecting a reduction of approximately $190 million from the end of the first quarter. We continue to anticipate this balance will be fully reimbursed to Sanofi by the end of 2026.

製造和商業供應的補償是賽諾菲合作收入的另一個組成部分，為1.57 億美元，考慮到銷售的增加，被製造效率所抵消，我們仍然預計2024 年製造和商業供應的補償將與2023 年全年相當基礎。第二季末賽諾菲開發餘額約20億美元，較第一季末減少約1.9億美元。我們仍然預計這筆餘額將在 2026 年底前全額償還給賽諾菲。

Moving to Bayer. Second quarter ex-US net sales of EYLEA and EYLEA 8 mg were $908 million, up 8% on a constant currency basis versus the prior year. Total Bayer collaboration revenue was $375 million, of which $353 million related to our share of net profits outside the US.

搬到拜耳。第二季 EYLEA 和 EYLEA 8 mg 在美國以外的淨銷售額為 9.08 億美元，以固定匯率計算比上年增長 8%。拜耳合作總收入為 3.75 億美元，其中 3.53 億美元與我們在美國以外的淨利潤份額有關。

Now to our operating expenses. Second quarter R&D expense grew 10% year-over-year to $1.1 billion, reflecting continued investments to support our robust pipeline, including late-stage oncology and hematology programs. We continue to make thoughtful investments to enable us to move quickly into Phase III programs is supported by data readouts anticipated over the next 12 to 18 months.

現在我們的營運費用。第二季研發費用年增 10% 至 11 億美元，反映出為支持我們強大的產品線（包括後期腫瘤學和血液學計畫）而持續進行的投資。我們繼續進行深思熟慮的投資，使我們能夠快速進入第三階段計劃，並得到未來 12 至 18 個月預計數據讀數的支持。

SG&A grew 19% from the prior year to $666 million in the second quarter, primarily driven by investment to support the launch of EYLEA HD as well as our ongoing international commercial expansion. Second quarter gross margin and net product sales was approximately 89%, which reflected ongoing start-up costs for our fill/finish manufacturing facility.

第二季的SG&A 較上年增長 19%，達到 6.66 億美元，這主要是由支持 EYLEA HD 推出以及我們正在進行的國際商業擴張的投資所推動的。第二季的毛利率和產品淨銷售額約為 89%，這反映了我們的填充/成品製造工廠的持續啟動成本。

Now to cash flow and the balance sheet. Regeneron generated approximately $1.6 billion in free cash flow through the first six months of 2024 and ended the quarter with cash and marketable securities less debt of approximately $14.8 billion. We repurchased approximately $900 million of our shares through the first six months of the year and had approximately $3.6 billion available for repurchases as of the end of the second quarter.

現在來看看現金流量和資產負債表。 Regeneron 在 2024 年前六個月產生了約 16 億美元的自由現金流，本季末現金和有價證券減去債務約為 148 億美元。今年前六個月，我們回購了約 9 億美元的股票，截至第二季末，我們還有約 36 億美元可用於回購。

Finally, we have made some minor changes to our full year 2024 financial guidance. We have updated our 2024 gross margin guidance and now expect gross margin to be approximately 89%, primarily reflecting anticipated changes in product mix as well as higher non-product specific costs, including start-up costs for our fill/finish facility. A complete summary of our latest full year guidance is available in our press release issued earlier this morning. In summary, Regeneron delivered outstanding results in the second quarter and is well positioned to continue to drive growth in the near and long-term.

最後，我們對 2024 年全年財務指引進行了一些細微調整。我們更新了 2024 年毛利率指引，目前預計毛利率約為 89%，主要反映了產品結構的預期變化以及更高的非產品特定成本，包括我們的灌裝/包裝設施的啟動成本。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。總而言之，再生元在第二季度取得了出色的業績，並有能力繼續推動近期和長期的成長。

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

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. Shannon, can we go to the first question, please?

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徵集。為了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。 Shannon，我們可以回答第一個問題嗎？

(Operator Instructions) Tyler Van Buren, TD Cowen.

（操作員說明）Tyler Van Buren，TD Cowen。

Hey, guys. Good morning. Congratulations on the great quarter. Regarding the EYLEA franchise, I'm really encouraged to see that the overall franchise is up year-over-year and that the 45% category share is maintained quarter-over-quarter. So do you believe that EYLEA HD is reaching a stage and maturity of its launch, where it will allow the overall category share to be relatively stable in the coming quarters that will allow you to participate in the retinal disease market growth and is the market still growing around 10% year-over-year?

大家好。早安.恭喜這個偉大的季度。關於 EYLEA 特許經營權，我真的很高興看到整體特許經營權同比增長，並且 45% 的類別份額環比保持不變。那麼您是否認為 EYLEA HD 已達到其推出的階段和成熟度，這將使整體類別份額在未來幾個季度相對穩定，這將使您能夠參與視網膜疾病市場的成長，並且該市場仍然存在嗎？增長10%左右？

So Tyler, I'll take it in a couple of pieces. Thank you for the question. First, I did want to comment, we were very pleased to report the total net sales of 1.4 -- excuse me, $1.54 billion in the quarter. Obviously, as you mentioned, that's a 2.4% increase year-over-year.

泰勒，我會把它分成幾個部分。感謝你的提問。首先，我確實想評論一下，我們非常高興地報告本季的總淨銷售額為 1.4——對不起，為 15.4 億美元。顯然，正如您所提到的，同比增長 2.4%。

Additionally, I'll just comment a little bit more on EYLEA HD. We certainly are very much in the launch stage. This is our third full quarter of results that we're reporting today. And certainly, we're encouraged that in the quarter, we had a 52% increase in net sales. And certainly, that calculation represents $100 million net sales increase from the prior quarter, which is very significant in this competitive market.

另外，我將對 EYLEA HD 進行更多評論。我們當然還處於啟動階段。這是我們今天報告的第三個完整季度的業績。當然，令我們感到鼓舞的是，本季我們的淨銷售額成長了 52%。當然，這項計算顯示淨銷售額比上一季增加了 1 億美元，這在這個競爭激烈的市場中非常重要。

So certainly, we are continuing to progress our launch and see it is important. Certainly, EYLEA is an important source of switch patients for EYLEA HD. Next, we see switches coming from faricimab, also Avastin, very pleased as well this quarter to report that we're seeing increased use of EYLEA HD in naive patient population. So all-in-all, we see this indicative that EYLEA HD has the potential and certainly the profile to be the new standard-of-care.

當然，我們正在繼續推進我們的發布，並認為這很重要。當然，EYLEA是EYLEA HD轉換患者的重要來源。接下來，我們看到來自 faricimab 的轉換，也是 Avastin，本季也非常高興地報告說，我們看到 EYLEA HD 在初治患者群體中的使用增加。總而言之，我們認為這表明 EYLEA HD 具有成為新護理標準的潛力，當然也有其特點。

I think you also asked me about market growth, overall market growth. Let me cover that as well. I would say probably at this stage in the year, we're tracking more on single-digit growth in the category in the midrange as opposed to double-digit, which I think is what was cited in your question.

我想你也問過我關於市場成長、整體市場成長的問題。讓我也介紹一下。我想說，可能在今年的這個階段，我們更多地追蹤中檔類別的個位數成長，而不是兩位數成長，我認為這就是您問題中引用的內容。

That's right. Okay. Thank you, Marion. Let's move to the next question please.

這是正確的。好的。謝謝你，馬里昂。讓我們進入下一個問題。

Evan Seigerman, BMO Capital Markets.

Evan Seigerman，BMO 資本市場。

Hi, guys. Thank you so much for taking my question and always congrats on the progress. I want to touch on your work in obesity specifically with leptin. Can you just walk me through some of the rationale of moving this to a Phase II? I know that leptin had been controversial. Clearly, you saw some interesting data in earlier trials. But why do you want to add this on top of say, tirzepatide, versus using triple agonist that Lilly is doing some of the other trials. Thank you so much.

嗨，大家好。非常感謝您提出我的問題，並始終祝賀您的進展。我想談談您在肥胖方面的工作，特別是瘦素方面的工作。您能否向我介紹一下將其轉移到第二階段的一些理由？我知道瘦素一直存在爭議。顯然，您在早期試驗中看到了一些有趣的數據。但為什麼你想在替澤帕肽之上添加這個，而不是使用禮來公司正在做的其他一些試驗的三重激動劑。太感謝了。

Well, we have leptin going forward in a number of different programs. I believe the one that you're talking about is in combination with other weight loss agent. And that's based on results that suggest that the reason leptin doesn't work in normal obese patients is because in those patients who have a high degree of fat and are in fact on the upswing of their obesity profile, their leptin levels are very high.

嗯，我們在許多不同的項目中都在推進瘦素。我相信你所說的那種是與其他減肥劑結合使用的。這是基於以下結果：瘦素對正常肥胖患者不起作用的原因是，在那些脂肪含量高且肥胖程度實際上呈上升趨勢的患者中，他們的瘦素水平非常高。

They're already saturating. Once you undergo profound weight loss, the leptin levels drop and you may be getting into the range where the leptin is now providing a signal, which is creating an increased desire in the individual to each. And so in these patients, it may be that some of the weight loss is limited by decreases in the leptin, which is then driving increasing feeding type of behavior.

他們已經飽和了。一旦你經歷了嚴重的體重減輕，瘦素水平就會下降，你可能會進入瘦素現在提供訊號的範圍，這會增加個人對每個人的慾望。因此，在這些患者中，部分體重減輕可能受到瘦素減少的限制，而瘦素減少又導致了進食行為的增加。

So this might be and at least it's been shown in animal studies to be the situation where leptin might actually be playing an important role. So as you point out, in historical studies in stably obese patients, leptin is already saturated and giving more leptin may not have a benefit. But in these settings where there are falling leptin levels, the falling and low leptin levels may lead to a food-seeking drive and giving leptin in that setting may allow further weight loss on top of that obtained with these other agents, which tend to plateau at a certain point, and that plateau at least based on animal studies may be in part driven by these drops in the leptin. And these studies, as you know, are done in collaboration with a partnership with Lilly. So there -- so we're studying it in collaboration with their agent tirzepatide.

因此，這可能是，至少在動物研究中已經表明，瘦素實際上可能發揮重要作用。因此，正如您所指出的，在穩定肥胖患者的歷史研究中，瘦素已經飽和，給予更多的瘦素可能沒有好處。但在瘦素水平下降的這些環境中，瘦素水平下降和低水平可能會導致尋求食物的衝動，在這種情況下給予瘦素可能會在使用這些其他藥物獲得的體重基礎上進一步減輕體重，而體重往往會趨於穩定。如您所知，這些研究是與禮來公司合作完成的。所以我們正在與他們的藥物替澤帕肽合作研究它。

Thanks, George. Let's move to the next question.

謝謝，喬治。讓我們進入下一個問題。

Brian Abrahams, RBC Capital Markets.

布萊恩‧亞伯拉罕斯 (Brian Abrahams)，加拿大皇家銀行資本市場部。

Hey, good morning. Thanks for taking my question and congratulations on the quarter and all the progress. On linvo, as you prepare for the potential launch there, I'm curious the feedback you're getting on how docs may position it relative to existing therapies, how much appreciation there is out there for the efficacy and administration advantages that you cited in your slide? And maybe you could also elaborate a little bit more on some of the issues with the third-party facility and they're confident if that's resolved. Thanks.

嗨，早安。感謝您提出我的問題，並祝賀本季和所有進展。在 linvo 上，當您為潛在的推出做準備時，我很好奇您收到的反饋，關於文檔如何相對於現有療法定位它，以及您在 中提到的功效和管理優勢有多少讚賞。的幻燈片？也許您也可以詳細說明第三方設施的一些問題，如果問題得到解決，他們很有信心。謝謝。

I'll take the third-party issue and George can cover or Marion, how people are thinking about a BCMA approach and where it might fit in the longer term. There's been a lot of third-party filler type and manufacturing issues with lots of CRLs across our, the biopharmaceutical space.

我將討論第三方問題，George 或 Marion 可以介紹人們如何考慮 BCMA 方法以及它在長期內可能適用的情況。在我們的生物製藥領域，大量 CRL 存在大量第三方填充劑類型和製造問題。

As you know, we had one last year with HD EYLEA and this was a case where the FDA was inspecting our filler for a different product. And they found some observations the observation is needed to be remediated, but because of the nature of the observations, a reinspection is necessary, we believe, based on what we've been told is that the observations have been remediated. But since there's a reinspection required, it might not get done, it's likely not to get done in time for our PDUFA date. That's why we called your attention to that.

如你所知，去年我們與 HD EYLEA 進行了一次合作，這次 FDA 正在檢查我們的填充劑是否有不同的產品。他們發現一些觀察結果需要補救，但由於觀察結果的性質，我們認為，根據我們被告知的觀察結果已得到補救，重新檢查是必要的。但由於需要重新檢查，因此可能無法完成，也可能無法在 PDUFA 日期之前及時完成。這就是為什麼我們提請您注意這一點。

This is an industry-wide issue. I think the FDA is, in fact, having planning some public hearing on these sorts of things. We're working with the FDA because this is a priority review application to see how we can resolve this in this expeditious manner as possible.

這是一個全行業的問題。我認為 FDA 事實上正在計劃就此類事情舉行一些公開聽證會。我們正在與 FDA 合作，因為這是一項優先審查申請，以了解我們如何以盡可能迅速的方式解決這個問題。

George or Marion, do you want to cover these?

喬治或瑪莉安，你想報道這些嗎？

Yes, I'll start and then I'll hand it over to Marion. But as we summarize and we've detailed and as we'll continue to be presented, the efficacy data with our bispecific continues to look like it is leading the field as the data matures, and patients continue on treatment, they continue to progress to deeper and deeper responses and where now we have complete response rates at 50% with, we believe, best-in-class PFS and overall survival type numbers.

是的，我先開始，然後把它交給馬里昂。但正如我們總結、詳細介紹以及我們將繼續介紹的那樣，隨著數據的成熟，我們的雙特異性藥物的療效數據看起來仍然處於領先地位，並且患者繼續接受治療，他們繼續進展到越來越深入的反應，現在我們的完全反應率為50%，我們相信，PFS 和總體生存類型數字是一流的。

This is obviously really important because what cancer treatment is all about is trying to eliminate the cancer and getting long-term durable responses and survival in the patients. And we would imagine that this is exactly what patients and physicians are focused about. Other aspects of our profile, we also believe in terms of safety and our dosing schedule and hospitalization burden also, we believe, are best-in-class. In terms of how Marion believes the physician community is appreciating the data, I'll ask Marion to comment on that.

這顯然非常重要，因為癌症治療的目的是試圖消除癌症並獲得長期持久的反應和患者的生存。我們可以想像，這正是病人和醫師所關注的問題。我們也相信，在我們的其他方面，我們的安全性、給藥方案和住院負擔也是一流的。至於馬里昂認為醫生界如何欣賞這些數據，我將請馬里昂對此發表評論。

Thanks, George. And certainly, we're very excited about the potential upcoming approval for linvoseltamab. George describes the differentiated clinical efficacy, safety profile that will be incredibly important to physicians. We have a highly experienced hematology team in place and ready for launch.

謝謝，喬治。當然，我們對 linvoseltamab 即將獲得批准感到非常興奮。喬治描述了差異化的臨床療效和安全性，這對醫生來說非常重要。我們擁有一支經驗豐富的血液學團隊，隨時準備推出。

Yes, I would just add, this is Len. I would just add that we're not limiting ourselves, obviously, just to the last line. We are trying to move this aggressively either in monotherapy or in combinations to much early lines of therapy.

是的，我想補充一點，這是萊恩。我想補充一點，顯然我們並沒有將自己限制在最後一行。我們正在嘗試透過單一療法或聯合療法積極地將其轉移到早期的治療中。

The rule of thumb has been in cancer that you tend to get more responses as you move to earlier lines. But this would be quite remarkable given what George just told you about the amount of responses we're seeing in the last line. So we're very excited about moving this forward and we'll go -- we'll keep you updated as we do that.

在癌症中，經驗法則是，當您移至較早的線路時，您往往會得到更多的反應。但考慮到喬治剛剛告訴你我們在最後一行看到的回覆數量，這將是相當引人注目的。因此，我們對推動這一進程感到非常興奮，我們會繼續這樣做，我們會隨時向您通報最新情況。

Yes. Just a follow-up on what Len said, obviously, this is why we're moving to these trials in these earlier lines of therapy. Obviously, we won't be commercializing those areas until we get the results from those clinical trial.

是的。顯然，這只是萊恩所說的後續行動，這就是我們在這些早期療法中進行這些試驗的原因。顯然，在我們得到這些臨床試驗的結果之前，我們不會將這些領域商業化。

Sure. Absolutely.

當然。絕對地。

All right, gentlemen. Let's go to the next question.

好吧，先生們。讓我們進入下一個問題。

Cory Kasimov, Evercore ISI.

科里·卡西莫夫，Evercore ISI。

Thank you, guys. Good morning. Thanks for taking the question. So we're getting an increasing amount of inbound interest in your Factor XI program. Can you speak to the differences, I guess, probably for George between your two antibodies? And what will be the key aspects you'll be focused on in your upcoming readouts to know you're on the right track? Thank you.

感謝你們。早安.感謝您提出問題。因此，我們對您的 Factor XI 計劃產生了越來越多的興趣。我想，您能談談您的兩種抗體之間可能對喬治來說的差異嗎？在即將到來的讀數中，您將重點關注哪些關鍵方面，以確保您走在正確的軌道上？謝謝。

Yes. So very importantly, what we've done is we've created antibodies that split the mechanism of action. One affects the activation domain, the other the catalytic domain. We have developed in both these classes, the only ones in class or the best-in-class type of antibodies, which are best at actually hitting and inhibiting that target based on all of the signs, a huge amount of genetics in part fortified by our own Regeneron genetics efforts and so forth, it suggests that these two approaches will allow us to separate and optimize optimum efficacy and optimum safety.

是的。因此非常重要的是，我們所做的是我們創造了能夠分解作用機制的抗體。一個影響活化域，另一個影響催化域。我們在這兩類抗體中都開發了同類中唯一的或同類中最好的抗體，它們最擅長根據所有跡象實際擊中和抑制該目標，大量的遺傳因素在一定程度上得到了加強我們自己的再生元遺傳學工作等等，這表明這兩種方法將使我們能夠分離和優化最佳功效和最佳安全性。

So it's quite possible that we might actually move forward with both of these antibodies for different target populations in some of which where efficacy is the primary driver and others where safety might be most important. So they're very unique in their mechanisms of action. They really are exploring this target both much more precisely by splitting the mechanism of action, but also more powerfully than competitors that have antibodies that can do one or the other of these things.

因此，我們很可能實際上會針對不同的目標族群推出這兩種抗體，其中一些族群的功效是主要驅動力，而有些族群的安全性可能是最重要的。因此它們的作用機制非常獨特。他們確實透過分解作用機制更精確地探索了這一目標，而且比擁有可以完成其中一項或另一項任務的抗體的競爭對手更強大。

So we're very excited about these programs. As we said, we have some proof-of-concept studies ongoing, and we hope by the end of the year to be able to announce the directions we may be taking either or both of these antibodies going forward in the future.

所以我們對這些計劃感到非常興奮。正如我們所說，我們正在進行一些概念驗證研究，我們希望在今年年底之前能夠宣布我們未來可能採取的這兩種抗體中的一種或兩種的發展方向。

Thanks, George. Let's move to the next question, please, Shannon.

謝謝，喬治。讓我們進入下一個問題，香農。

Chris Raymond, Piper Sandler.

克里斯·雷蒙德，派珀·桑德勒。

Hey, thanks. And just a quick question on EYLEA and the commercial progress. So you guys, I think, were pretty clear in your messaging on the permanent J-code is we should not really see an inflection that was seen maybe with VABYSMO when they got their permanent J-code as there were some other variables such as discounting, et cetera, going on with that example.

嘿，謝謝。我想問一個關於 EYLEA 和商業進展的簡單問題。所以，我認為，你們在關於永久 J 代碼的消息中非常清楚，我們不應該真正看到當他們獲得永久 J 代碼時可能在 VABYSMO 中看到的變化，因為還有一些其他變量，例如折扣等等，繼續那個例子。

But we've gotten some market feedback that access barriers remain even with the J-code change and specifically among Medicare Advantage plans. Marion, I'm curious if you can talk about the dynamic there and how you see things playing out with respect to access post permanent J-code.

但我們得到的一些市場回饋表明，即使 J 代碼發生變化，准入障礙仍然存在，特別是在 Medicare Advantage 計劃中。 Marion，我很好奇您能否談談那裡的動態以及您如何看待訪問永久 J 代碼後的情況。

Sure. I'm very, very happy to comment. So certainly, for a portion of the market, fee-for-service Medicare patients, there's open access and freedom of prescribing for physicians. If we go to those areas of the market where there's a payer impact, our teams have successfully opened access for EYLEA HD in a way that covers over 80% of patient lives.

當然。我非常非常高興發表評論。因此，當然，對於部分市場，即按服務收費的醫療保險患者來說，醫生有開放的准入和處方自由。如果我們進入那些對付款人有影響的市場領域，我們的團隊已經成功地開放了 EYLEA HD 的訪問權限，覆蓋了 80% 以上的患者生活。

So certainly, significant progress has been made and we continue to work through situations where physicians might be having some utilization management or step edits I will share that those are often easily managed when the physician and office staff provide information. But overall, the takeaway message should be that EYLEA HD has a very strong payer coverage. And again 80% of the market where reimbursement is in place.

因此，當然，已經取得了重大進展，我們將繼續解決醫生可能進行一些利用管理或步驟編輯的情況，我將分享當醫生和辦公室工作人員提供資訊時，這些通常很容易管理。但總體而言，重點應該是 EYLEA HD 擁有非常強大的付款人覆蓋範圍。 80% 的市場都實施報銷。

Thanks, Marion. Let's move to the next question, Shannon.

謝謝，馬里昂。讓我們進入下一個問題，香農。

Akash Tewari, Jefferies

阿卡什‧特瓦里，傑弗里斯

Hi. This is Kathy on for Akash. So for your myostatin program, can you talk about your preference for using a doublet versus triplet combination approach in your Phase III trials? And also where do you think myostatin will stack up versus GIP, GLP, amylin combination approaches, which could show potentially like 90% plus fat versus muscle loss. Thank you.

你好。這是阿卡什的凱西。那麼，對於您的肌肉生長抑制素計劃，您能談談您在 III 期試驗中對使用雙聯體與三聯體組合方法的偏好嗎？另外，您認為肌肉生長抑制素與 GIP、GLP、胰島澱粉樣多肽組合方法相比，效果如何，這些方法可能顯示 90% 以上的脂肪與肌肉損失相比。謝謝。

Yes. Well, once again, what we focused on is creating individual reagents that allow us to best dissect the pathway and separate out which are the most important players. As you're aware, other people, for example, are using an antibody that blocks all the pathways, not only the two that we've targeted, but about 20 others that are irrelevant for muscle and we know are known to have a variety of other potential side effects and adverse effects.

是的。好吧，我們再次關注的是創造單獨的試劑，使我們能夠最好地剖析該途徑並分離出最重要的參與者。如您所知，例如，其他人正在使用一種抗體來阻斷所有途徑，不僅是我們針對的兩條途徑，還有大約 20 種與肌肉無關的途徑，我們知道它們有多種途徑其他潛在的副作用和不利影響。

So we targeted the two muscle specific pathways in this whole mechanism. And what we want to see is which one might have the best efficacy to safety profile that we believe is very important. Once we determine that, we may move forward with either one or both of these antibodies in combination with the weight loss agents or we also have been developing in our pipeline, a variety of unimolecular solutions that will allow a single molecule to do whichever one of these multiple pathways we want to attack in addition to the weight loss pathway.

因此，我們針對整個機制中的兩條肌肉特定途徑。我們希望看到哪一種可能對我們認為非常重要的安全性具有最佳功效。一旦我們確定這一點，我們可能會繼續將這些抗體中的一種或兩種與減肥劑結合使用，或者我們也在我們的管道中開發各種單分子解決方案，這些解決方案將允許單個分子執行以下任一操作除了減肥途徑之外，我們還想攻擊這些多種途徑。

So what we're hoping to do is by dissecting the pathway as precisely and scientifically as possible, allow us to choose between the unimolecular solutions that we can have to follow on. That said, remember, it's not just a matter of amplifying the weight loss because with more weight loss, regardless of pathway you use, you can throw on the GLP-1 agonist, you can throw on GPR antagonist, you can lay on additional pathways. The more rate loss and the more rapidly occurs, which is what patients want, out of necessity because you're mimicking the starvation to get the pathway, it inevitably leads to muscle loss because of why, because of activation of these very pathways that we're looking at.

因此，我們希望做的是透過盡可能精確和科學地剖析該途徑，使我們能夠在我們必須遵循的單分子解決方案之間進行選擇。也就是說，請記住，這不僅僅是擴大體重減輕的問題，因為隨著體重減輕的增加，無論您使用哪種途徑，您都可以使用GLP-1 激動劑，您可以使用GPR 拮抗劑，您可以使用其他途徑。速率損失越多，發生得越快，這正是患者想要的，出於必要，因為你模仿飢餓來獲得途徑，它不可避免地導致肌肉損失，因為為什麼，因為這些途徑的激活，我們正在看。

So any approach right now that focuses on rapidly causing weight loss will of necessity because it plugs into evolutionarily conserved pathways of necessity will result in profound lean body and muscle loss, which can be a huge detriment to these patients especially the older obese patient. And by invoking these agents blocking these specific pathways, we may be able to do two things. We may block this associated necessarily evolutionary conserved muscle loss that accompanies rapid and profound weight loss while also perhaps increasing the amount of fat loss, which is what you specifically want to lose.

因此，目前任何專注於快速減肥的方法都是必要的，因為它插入了進化上保守的必要途徑，將導致嚴重的瘦身和肌肉損失，這可能對這些患者，尤其是老年肥胖患者造成巨大損害。透過調用這些阻斷這些特定途徑的藥物，我們也許能夠做兩件事。我們可以阻止這種必然與演化相關的保守性肌肉損失，而這種損失伴隨著快速而深刻的體重減輕，同時也可能增加脂肪減少的量，這正是你特別想減掉的。

This is what we've now shown in preclinical studies, including through nonhuman primates and these studies that we're embarking on right now should tell us whether all of these pathways, which are incredibly evolutionarily conserved will indeed pertain in humans and whether we really can optimize not only the weight loss, that's not what's important, but optimize particularly fat loss while maintaining the muscle. And we believe we're the only ones who are properly precisely interrogating the pathways and we'll be able to dissect them to decide on which exactly is the best, safest pathway to give the best benefit to the patient.

這就是我們現在在臨床前研究中所展示的內容，包括透過非人類靈長類動物進行的研究，我們現在正在進行的這些研究應該告訴我們，所有這些在進化上極其保守的途徑是否確實適用於人類，以及我們是否真的不僅可以優化減肥，這不是最重要的，而且可以在保持肌肉的同時優化特別是脂肪的減少。我們相信，我們是唯一能夠正確、精確地研究這些途徑的人，我們將能夠剖析它們，從而決定哪一條才是最好、最安全的途徑，為病人帶來最大的利益。

Okay. Thanks, George. Shannon, next question, please.

好的。謝謝，喬治。香農，請下一個問題。

Chris Schott, JPMorgan

克里斯‧肖特，摩根大通

Great. Thanks so much for the question. Just on linvo, Dupixent and food allergy. I know it's early but an exciting program. Can you help us just a bit to frame out the number of patients or percent of those with food allergy where you think this could be an appropriate treatment if the data we see later this year and going forward supports moving that combination forward? Thanks so much.

偉大的。非常感謝您的提問。只是關於 linvo、Dupixent 和食物過敏。我知道現在還早，但這是一個令人興奮的計劃。如果我們今年稍後和未來看到的數據支持推動這種組合的發展，您能否幫助我們確定您認為這可能是適當治療的患者數量或食物過敏患者的百分比？非常感謝。

I think that it's all going to be a matter of the benefit to risk profile once again. And this is what, as I've said in these other programs we're focusing on. We believe, based on all the data that we've shown, that we may have a very safe way of eliminating the actual cells that are causing all these allergic responses and then very safely keep them from coming back by giving one of the world's historically most safe biologics, which is Dupixent. Of course, we have to prove this in patients.

我認為這一切都將再次取決於收益與風險狀況的關係。正如我在其他計劃中所說，這就是我們關注的重點。我們相信，根據我們所展示的所有數據，我們可能有一種非常安全的方法來消除引起所有這些過敏反應的實際細胞，然後透過給予世界歷史上最安全的細胞之一來非常安全地防止它們回來。最安全的生物製劑，那就是Dupixent。當然，我們必須在患者身上證明這一點。

And so we are starting in the most severe food allergy patients. And in these patients where they have, for example, very high unmet need, very high risks and so forth, it warrants undertaking this approach. The more effective it is, but more importantly, the safer we can prove it is then the broader the population can go. And in fact, if ultimately, we really have a very safe way of eliminating all allergy inducing cells and then preventing their rebound.

因此，我們從最嚴重的食物過敏患者開始。例如，在這些患者中，他們有非常高的未滿足需求、非常高的風險等，因此有必要採取這種方法。它越有效，但更重要的是，我們可以證明它越安全，那麼可以涵蓋的人群就越廣泛。事實上，如果最終的話，我們確實有一種非常安全的方法來消除所有過敏誘導細胞，然後防止它們反彈。

And remember, particularly, most of these patients are also suffering from other allergic diseases, some of them may already be indicated for Dupixent. So you're giving them a drug which may actually be helping them anyway and has been shown to be quite safe in terms of as almost any biologic goes. We may be able to go into milder and milder allergy patients. So we can start and we are starting with the most severe patients we're seeing in these patients with a high unmet need, whether this approach is both effective, but also safe and how safe it is and the safer it is, we can broaden wider and wider.

請特別記住，這些患者中的大多數還患有其他過敏性疾病，其中一些可能已經適合使用 Dupixent。因此，您給他們的藥物實際上可能對他們有幫助，並且已被證明與幾乎所有生物製劑一樣非常安全。我們也許能夠進入越來越輕微的過敏患者。因此，我們可以開始，我們從我們所看到的最嚴重的患者開始，這些患者的需求未得到滿足，這種方法是否既有效，又安全，以及它的安全性如何，越安全，我們可以擴大範圍越來越寬。

There's also ultimately no need to be limited to food allergies, you can actually eliminate essentially all allergies from the most serious to the most mundane, but it depends on the benefit risk and the safety, which is what we're testing in these initial studies. And for the initial studies, we're taking the most severe food-allergic patients who have a very high unmet need and very high-risk profile depending on how it goes there, we can broaden to milder and milder types of disease.

最終也沒有必要僅限於食物過敏，實際上您可以消除從最嚴重到最普通的所有過敏，但這取決於效益風險和安全性，這就是我們在這些初步研究中測試的內容。對於初步研究，我們正在研究最嚴重的食物過敏患者，他們的需求未得到滿足非常高，風險狀況也非常高，具體取決於其進展情況，我們可以擴展到越來越輕微的疾病類型。

I mean the numbers I get are quite staggering. Looking at -- if you just look at the number of emergency room visits a year, it could be hundreds of thousands of millions of people go to the emergency room for food-based allergies. Obviously, a smaller number for actual anaphylaxis.

我的意思是我得到的數字相當驚人。看看——如果你只看每年急診室就診的人數，可能有數十億人因食物過敏而去急診室。顯然，實際過敏反應的數字較小。

But just to reinforce exactly what George says, if all it takes is an induction in BCMA to induce the process where you can get on to Dupi, Dupi is a very safe agent, and we've got hundreds of thousands, approaching million of patients on the drug. So we know the profile of that drug. So this is all makes great scientific sense. We just have to take our time, do it safely and see how it develops.

但為了準確地強調 George 所說的，如果只需在 BCMA 中進行誘導即可誘導進入 Dupi 的過程，那麼 Dupi 是一種非常安全的藥物，我們已經有數十萬、接近數百萬患者關於藥物。所以我們知道該藥物的概況。所以這一切都有很大的科學意義。我們只需要慢慢來，安全地進行，看看它如何發展。

Thanks, Len and George. Let's move to the next question, please.

謝謝，萊恩和喬治。請讓我們進入下一個問題。

Tim Anderson, Wolfe Research.

蒂姆·安德森，沃爾夫研究中心。

Thank you very much. I have a question on EYLEA and this DOJ investigation into the marketing practices that emerged since April, where they assert that you guys violate the False Claims Act. Can you provide an update on what happens from here, specifically in the interim and out of prudence, has Regeneron changed any of its marketing practices since April. And is that having any impact even on prescribers. I asked because on Slide 6, you mentioned, other market dynamics that resulted in lower volumes and lower price. I am just wondering what those where.

非常感謝。我有一個關於 EYLEA 和 DOJ 對自 4 月以來出現的營銷行為的調查的問題，他們聲稱你們違反了《虛假申報法》。您能否提供有關此後發生的情況的最新信息，特別是在過渡期間和出於謹慎考慮，再生元自 4 月份以來是否改變了其營銷實踐。這甚至對處方者也有影響嗎？我問這個問題是因為在幻燈片 6 上，您提到了其他導致銷售下降和價格下降的市場動態。我只是想知道那些在哪裡。

There's nothing in the marketplace related to this lawsuit. And frankly we think there's nothing to this lawsuit. And we have not changed our practice, and we intend to fight it vigorously. And I think once you see our papers in court, you'll get a much better understanding of that.

市場上沒有任何與此訴訟相關的資訊。坦白說，我們認為這起訴訟沒有任何意義。我們的做法也沒有改變，我們打算大力打擊。我認為，一旦您在法庭上看到我們的文件，您就會對此有更好的理解。

David Risinger, Leerink Partners

大衛‧瑞辛格（David Risinger），Leerink Partners

Yes. Thanks very much. So Regeneron is obviously a tremendous R&D leader, but there's also substantial innovation happening outside of the company, and the company has a tremendous balance sheet that it's not really putting to work. So my question is, is there an opportunity to leverage Regeneron's eye disease commercial presence by acquiring novel potential blockbuster therapies for severe eye disease. And if so, does the company see any opportunities in the near to medium term to do so? Thanks very much.

是的。非常感謝。因此，再生元顯然是一家龐大的研發領導者，但公司外部也發生了大量創新，而且該公司擁有龐大的資產負債表，但尚未真正投入使用。所以我的問題是，是否有機會透過收購治療嚴重眼疾的新型潛在重磅療法來利用再生元的眼疾商業存在。如果是這樣，公司在中短期內是否看到了這樣做的機會？非常感謝。

Yes, it's a great question, and it's one we ask every day here. Is there some opportunity that we are -- isn't resulting from our own innovation that we should be trying to acquire. We have not seen any such large scale. Obviously, we've done some smaller scale and hundreds of millions of kind of numbers or a few million and whether or not we would -- we could leverage any of our in-line products or research capabilities, it's certainly something we think about, but there's nothing that we at the moment for late-stage products see an opportunity for.

是的，這是一個很好的問題，也是我們每天都會問的問題。我們是否有一些機會不是來自於我們自己的創新，而我們應該努力獲得這些機會。我們還沒有見過如此大規模的。顯然，我們已經做了一些較小規模的數據，數億或幾百萬，無論我們是否可以利用我們的任何在線產品或研究能力，這肯定是我們考慮的事情，但目前我們認為後期產品沒有任何機會。

Thanks, Len. Let's move to the next question, please, Shannon.

謝謝，萊恩。讓我們進入下一個問題，香農。

Salveen Richter, Goldman Sachs.

薩爾文·里克特，高盛。

Good morning. Thanks for taking my question. On the Factor XI programs here, could you speak to the potential commercial opportunity that are represented and what the future development plans look like here? Thank you.

早安.感謝您提出我的問題。關於這裡的 Factor XI 計劃，您能否談談所代表的潛在商業機會以及未來的發展計劃？謝謝。

Well, as I said, we're in the stages of evaluating our Factor XI two classes of antibodies that are attacking this pathway in two different ways. We expect I think we've already talked about. One of them will be more effective at preventing clot formation, but potentially come with slightly more serious side effect profiles. The other might be less effective, but much safer.

嗯，正如我所說，我們正處於評估因子 XI 的兩類抗體的階段，它們以兩種不同的方式攻擊這一途徑。我們預計我想我們已經討論過了。其中一種可以更有效地防止血栓形成，但可能會帶來稍微嚴重的副作用。另一種可能效果較差，但更安全。

And as I said, we thought it was important to really precisely interrogate this pathway using these two antibodies that are attacking, two different parts. So this is one enzyme. It has an activation domain, a catalytic domain. And by blocking independently the two different domains, we expect to deliver two different profiles each one with the best-in-class antibody.

正如我所說，我們認為使用這兩種攻擊兩個不同部分的抗體來真正精確地詢問該通路非常重要。所以這是一種酵素。它有一個活化域，一個催化域。透過獨立阻斷兩個不同的結構域，我們期望提供兩種不同的配置文件，每種配置都具有一流的抗體。

Once we really understand those profiles, we will understand in which directions to be taken either one or both potentially in antibodies. We can easily imagine taking forward, the more effective one, but for a higher-risk patients, let's say, the less effective one into settings where you might want more safety and clot prevention is not as important. So all of this is going to depend on these profiles.

一旦我們真正了解了這些概況，我們就會了解抗體中的一個或兩個可能採取的方向。我們可以很容易地想像採用更有效的方法，但對於風險較高的患者來說，可以說，將效果較差的方法轉移到您可能需要更多安全性且預防血栓不那麼重要的環境中。所以所有這一切都將取決於這些設定檔。

And as I said, we hope to get our key data by the end of this year, and that should better define the efficacy and safety profile how they compare to the various existing agents that are out there now and which direction to take them for which indication. So two antibodies, two distinct profiles we hope to better understand them based on our initial proof-of-concept study.

正如我所說，我們希望在今年年底之前獲得關鍵數據，這應該可以更好地定義它們與現有各種現有藥物的療效和安全性概況，以及將它們帶入哪個方向指示。因此，兩種抗體，兩種不同的特徵，我們希望根據我們最初的概念驗證研究來更好地理解它們。

And from there, we'll understand where to take them and what the ultimate opportunity will be. But obviously there's still enormous need here for agents that can block, clot and thrombus formation. And so much depends on safety profiles here, and we're very excited about having the opportunity to have these two very related but distinct profiles.

從那裡，我們將了解將它們帶到哪裡以及最終的機會是什麼。但顯然，這裡仍然非常需要能夠阻斷、凝結和血栓形成的藥物。這裡很大程度上取決於安全配置文件，我們非常高興有機會擁有這兩個非常相關但又不同的配置文件。

Just to amplify a little bit of what George said the direct oral anticoagulant market is a very, very large market. It's about a $20 billion market. if you could bring to part of that market, most of that market or some fragment similar efficacy, but with a better safety profile then you really have a big opportunity here. So that's what we're focusing on.

只是為了放大一點喬治所說的直接口服抗凝血劑市場是一個非常非常大的市場。這是一個價值約200億美元的市場。如果你可以為部分市場、大部分市場或某些片段帶來類似的功效，但具有更好的安全性，那麼你真的有很大的機會。這就是我們關注的重點。

Can we deliver with one or the other antibody in the proper setting, as George was suggesting a same or better efficacy, but with a better safety profile. If we can give you that, if we can give patients that, then we will be able to really have a big, large market opportunity.

我們能否在適當的環境下使用一種或另一種抗體，正如喬治所建議的那樣，具有相同或更好的功效，但具有更好的安全性。如果我們能夠為您提供這一點，如果我們能為患者提供這一點，那麼我們將能夠真正擁有一個巨大的市場機會。

And there are many settings where you don't use certain agents because of the safety profile, which could create whole new opportunities as well.

在許多情況下，由於安全原因，您不使用某些代理，這也可能創造全新的機會。

Okay. Thank you. Let's move to the next question please, Shannon.

好的。謝謝。香農，讓我們進入下一個問題。

Carter Gould, Barclays

卡特·古爾德，巴克萊銀行

Good morning. Congrats on the quarter. I appreciated the earlier commentary from Len on the pre-filled syringe effort, I guess, but for Marion and the team, just the confidence that the high dose launch momentum won't be disrupted by the relative near-term disadvantage of VABYSMO having a pre-filled syringe and if you wanted to give more specificity on your own timelines, that would be appreciated. Thank you.

早安.恭喜本季。我想，我很欣賞 Len 對預裝注射器工作的早期評論，但對於 Marion 和團隊來說，只有相信高劑量發射勢頭不會因為 VABYSMO 的相對近期劣勢而受到干擾。自己的時間表上提供更多具體信息，我們將不勝感激。謝謝。

Well, I think I said in my prepared remarks that we're anticipating a launch in early 2025. I'm not sure what the competition is actually going to do about launching, but we're a matter of months, I think, a part if they launch ahead of us. And so I don't think that that's going to have a significant impact in the marketplace where people really are focused, I think, on the profile of our drug, the durability of our drug, the safety experience they've had with aflibercept, the active ingredient. So we feel pretty confident in the ongoing launch.

好吧，我想我在準備好的發言中說過，我們預計在 2025 年初發布。於我們發射的話。因此，我認為這不會對市場產生重大影響，因為人們真正關注的是我們藥物的概況、我們藥物的耐用性以及他們使用阿柏西普的安全體驗，活性成分。因此，我們對正在進行的發布充滿信心。

Thank you. We have time for two more questions, please, Shannon.

謝謝。我們還有時間再問兩個問題，香農。

Terence Flynn, Morgan Stanley.

特倫斯‧弗林，摩根士丹利。

Hi. This is Chris on for Terence. Just one question from us about EYLEA HD. Given what you have seen in the market dynamics in 2Q. How should we think about the pace of conversion for the second half of 2024?

你好。這是克里斯替補特倫斯。我們只有一個關於 EYLEA HD 的問題。鑑於您在第二季的市場動態中看到的情況。我們該如何思考2024年下半年的轉型步伐？

You should think hard about it. That's your job. I don't know if Marion wants to have any comment there.

你應該認真思考一下。那是你的工作。我不知道馬里昂是否想對此發表評論。

I would just say that as I commented earlier, we're very pleased in our progress in the EYLEA HD launch.

我只想說，正如我之前評論的那樣，我們對 EYLEA HD 發布所取得的進展感到非常高興。

All right. Thank you. Let's move to the final question, please, Shannon.

好的。謝謝。讓我們進入最後一個問題，香農。

Mohit Bansal, Wells Fargo

莫希特‧班薩爾，富國銀行

Thank you very much for taking my question, Shannon. I just want to, again, talk about EYLEA HD. In terms of -- Marion, if you could comment on, at this point, how much is switch versus naive patient adjustment? I assume most of them are switch and are they difficult to treat patients in the beginning?

非常感謝您提出我的問題，香農。我只想再談談 EYLEA HD。就馬里昂而言，您是否可以評論一下，在這一點上，轉換與天真的患者調整相比有多少？我認為他們中的大多數都是轉換者，他們一開始就很難治療患者嗎？

And then when you think about going forward, do you think you're in the early innings of conversion? Or do you think there is some other dynamics we should think about from the pricing as well as access point of view as we model EYLEA HD versus standard dose EYLEA going forward? Thank you.

然後，當您考慮繼續前進時，您認為自己處於轉變的早期階段嗎？或者您認為，在我們對 EYLEA HD 與標準劑量 EYLEA 進行建模時，我們應該從定價和獲取的角度考慮其他一些動態？謝謝。

So it's always a combination of initiation for EYLEA HD of switch patients and then, of course, naive patients. So I'd mentioned the profile today of switch patients to EYLEA HD, which is very encouraging comes not surprisingly from EYLEA because it's the largest product in the category, secondarily from faricimab.

因此，EYLEA HD 的起始治療始終是轉換患者和初次接受治療的患者的組合。因此，我今天提到了將患者改用 EYLEA HD 的情況，這是非常令人鼓舞的，這來自 EYLEA 並不奇怪，因為它是該類別中最大的產品，其次是 Faricimab。

And then the third source of switch patients would be Avastin and then there's everything else. But what's really encouraging, as I mentioned in the quarter, is that the utilization among treatment-naive patients doubled from the prior quarter. So we'll continue to see an ongoing combination as does every product potentially, if it's got the right profile in the category, but the evolution of prescribing to EYLEA HD is progressing very well.

第三個轉換患者來源是阿瓦斯汀，然後還有其他一切。但正如我在本季提到的，真正令人鼓舞的是，初次接受治療的患者的使用率比上一季翻了一番。因此，我們將繼續看到一種持續的組合，就像每個產品一樣，如果它在該類別中具有正確的配置，那麼 EYLEA HD 處方的演變進展非常順利。

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

謝謝馬里昂，也感謝今天撥電話的所有人對再生元的興趣。我們向那些留在問答隊列中沒有機會的人道歉——我們沒有機會收到消息。像往常一樣，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。

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

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。