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公司2024年第二季財報電話會議。我是Shannon，將擔任本次電話會議的接線生。 （接線生說明）請注意，本次電話會議正在錄音。

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

現在我將把電話交給投資者關係高級副總裁瑞安·克羅。您可以開始了。

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.

謝謝香農。各位全球聽眾，早安、下午好、晚上好。感謝大家對再生元公司的關注，歡迎參加我們2024年第二季財報電話會議。本次電話會議的錄音和文字記錄將在會議結束後不久發佈在 Regeneron 投資者關係網站上。

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

今天與我一起參加電話會議的有：董事會聯席主席、聯合創始人、總裁兼首席執行官 Leonard Schleifer 博士；董事會聯席主席、聯合創始人、總裁兼首席科學官 George Yancopoulos 博士；商業執行副總裁 Marion McCourt；以及高級副總裁兼首席財務官 Chris Fenimore。我們發言結束後，剩餘時間將留給各位提問。我們預計今天的電話會議將持續約 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.

我想提醒各位，今天電話會議上發表的言論可能包含 Regeneron 的前瞻性陳述。此類聲明可能包括但不限於與 Regeneron 及其產品和業務、財務預測和指導、開發計劃和相關預期里程碑、合作、財務、監管事項、支付方覆蓋範圍和報銷問題、智慧財產權、未決訴訟和其他程序以及競爭相關的聲明。每項前瞻性聲明都存在風險和不確定性，可能導致實際結果和事件與該聲明中預測的結果和事件有重大差異。

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.

有關這些及其他重大風險的更完整描述，請參閱 Regeneron 向美國證券交易委員會提交的文件，包括其截至 2024 年 6 月 30 日的季度 10-Q 表格，該表格已於今天上午提交給美國證券交易委員會。Regeneron不承擔任何更新任何前瞻性聲明的義務，無論是由於新資訊、未來事件或其他原因。

In addition, please note that GAAP and non-GAAP financial measures will be discussed on today's call. Information regarding our use of non-GAAP financial measures and a reconciliation of those measures to GAAP is available in our quarterly results, press release, and our corporate presentation, both of which can be 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報告、新聞稿和公司演示文稿，這些資料均可在 Regeneron 投資者關係網站上查閱。通話結束後，克里斯和投資者關係團隊將解答您提出的任何其他問題。

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

接下來，我將把電話交給我們的總裁兼執行長倫納德‧施萊弗博士。倫？

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.

謝謝你，瑞恩。感謝各位參加今天電話會議。再生元持續保持強勁的執行力，第二季營收和利潤均實現了兩位數成長，同時在廣泛的產品線中也取得了重要進展。

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.

今天，我想先簡單回顧本季的一些關鍵業績驅動因素，然後再討論近期的發展機會。我發言結束後，喬治將就我們的管道項目提供進一步的最新資訊。之後，瑪莉昂將對我們的商業業績進行評估。最後，克里斯將詳細介紹我們的季度財務業績，並討論我們全年業績指引的最新情況。

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% 至 35.5 億美元，主要得益於 EYLEA HD 在美國的銷售。賽諾菲合作收入增加，反映出Dupixent持續強勁的表現以及Libtayo的穩健成長。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，並繼續在抗 VEGF 類別中超越近期推出的產品。EYLEA HD 和 EYLEA 合計淨產品銷售額為 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.

儘管抗 VEGF 領域的競爭日益激烈，但我們仍然取得了 EYLEA HD 的強勁上市勢頭，同時保持了 EYLEA HD 和 EYLEA 45% 的市場份額，在同類產品中處於領先地位，這令我們倍感鼓舞。我們致力於將 EYLEA HD 預充式註射器引入美國市場，並將繼續把這一目標放在首位，我們正朝著 2025 年初推出預充式註射器的目標穩步邁進。總之，基於其差異化的臨床特徵，以及視網膜專家的高度熟悉和滿意度，我們繼續將 EYLEA HD 定位為視網膜疾病的新標準治療方案。

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% 至 35.6 億美元，反映出其在所有獲準適應症、年齡層和地區均實現了強勁成長。6 月，歐盟委員會批准 Dupixent 用於治療血液嗜酸性粒細胞增多的 COPD 患者，這標誌著 Dupixent 首次獲得全球監管機構批准用於治療 COPD。此次獲準使 Dupixent 能夠幫助歐盟約 22 萬名嗜酸性 COPD 患者，這些患者目前即使接受最大劑量和符合條件的治療也無法控制病情。該藥物的核准也標誌著首個獲準用於治療該疾病的生物製劑問世。

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 合作，討論其對該適應症的持續審查，並期待他們在 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做好準備，迎接許多肺科醫生、呼吸系統領域的意見領袖及其患者翹首以盼的美國市場上市。在美國，COPD 2 型發炎領域存在著巨大的未滿足需求，約有 30 萬名符合條件的患者，而我們潛在的產品上市將顯著推動 Dupixent 的持續成長。

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 第二季全球淨產品銷售額為 2.97 億美元，以固定匯率計算成長了 43%。儘管競爭激烈，Libtayo 仍保持在非黑色素瘤皮膚癌領域的領先地位，同時在非小細胞肺癌領域取得了令人矚目的進展。我們也對在建立國際商業佈局方面取得的進展感到滿意，這將支持 Libtayo 和其他未來產品。在此之前，我們在 2022 年年中從賽諾菲收購了 Libtayo 的全部全球權利。

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.

關於使用 linvoseltamab 或 BCMA 以 CD3 雙特異性抗體治療復發難治性多發性骨髓瘤。在審查 linvoseltamab BLA 時，FDA 通知我們，linvoseltamab 的第三方灌裝生產商在另一家公司的產品候選藥物的上市前檢查中發現了一些尚未解決的問題。

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.

雖然我們現在認為這些問題已經解決，但仍需要重新檢查。因此，我們預計 linvoseltamab 獲得 FDA 批准的任何可能性都可能會推遲到 8 月 22 日 PDUFA 日期之後。FDA尚未告知我們任何與linvoseltamab的安全性、有效性或我們正在進行的驗證性試驗狀態相關的可批准性問題。更廣泛地說，就我們的研發管線而言，我們對今年晚些時候或 2025 年即將公佈的幾項數據感到興奮，這些數據將進一步為可能支持重大長期增長機會的項目提供信息，喬治稍後將對此進行討論。

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，我們的研發管線不斷創造創新和差異化的機會，目前已有超過 35 個計畫處於臨床開發階段，涵蓋多個不同的治療領域。我們的銷售團隊在市場推廣產品方面表現出色，並在競爭激烈的類別中持續累積優勢。最後，我們將繼續審慎地運用資本，以期為股東創造長期價值。

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

這樣，我就把電話交給喬治了。

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，Len。從Dupixent開始。關於 COPD，我們第二次驗證性試驗 NOTUS 的數據在美國胸腔科學會會議上作為最新成果發表，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 研究中，Dupixent 將病情加重次數減少了 34%，同時顯著改善了肺功能，證實了先前報告的 III 期 BOREAS 試驗的空前結果。根據 NOTUS 和 BOREAS 的數據，Dupixent 最近獲得了歐洲監管機構的批准，用於治療接受最大標準吸入療法仍無法控制的嗜酸性 COPD 患者。其他提交的文件正在接受世界各地其他監管機構的審查，包括美國、中國和日本的監管機構。

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，我們還期待 Dupixent 在慢性自發性蕁麻疹和大皰性類天皰瘡 III 期研究中獲得數據結果。在首次獲得 FDA 批准後的七年裡，Dupixent 已在全球獲得七種不同適應症的批准，並繼續為其他重要疾病適應症帶來潛在的新批准。關於我們正在進行的小型試驗研究，旨在利用我們創新的方法（將 Dupixent 和 linvoseltamab 或 BCMA 透過 CD3 雙特異性抗體相結合）來消除嚴重的食物過敏，我們仍然期待在今年年底前看到初步數據。

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.

我們正在為某些 COPD 患者開發 IL-33 抗體 itepekimab，目前兩項 III 期研究已全部完成招募。針對這種毀滅性疾病的第二個候選療法的研究結果和監管文件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.

轉入腫瘤科，從 fianlimab 開始。在即將於 9 月舉行的 ESMO 會議上，我們期待展示我們的 LAG-3 抗體與 Libtayo 聯合療法，以及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。隨著完全緩解率和中位無惡化存活期的持續改善，治療效果不斷增強。

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那樣，我們期待明年在黑色素瘤治療中獲得 III 期結果，這可能會使 fianlimab 和 Libtayo 成為黑色素瘤治療的新標準，並最終有可能成為其他癌症治療的新標準。

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這種組合療法在非小細胞肺癌中的抗腫瘤活性。我們也正在推動 fianlimab 的早期治療研發，目前正在進行圍手術期非小細胞肺癌和圍手術期黑色素瘤的概念驗證，未來可能會有更多適應症。

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.

接下來是針對實體腫瘤的雙特異性抗體。我們的共刺激雙特異性抗體正在多項研究中進行測試，包括作為單一療法以及與 CD3 雙特異性抗體和 Libtayo 聯合使用。在 ASCO 會議上，我們展示了 EGFR by CD28 雙特異性抗體與 Libtayo 聯合應用的研究結果。對於以往對免疫療法無反應的微衛星穩定型結直腸癌腫瘤，CD28 標靶 EGFR 與 Libtayo 聯合治療顯示出令人鼓舞的抗腫瘤活性，在沒有肝轉移的患者中總緩解率為 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.

就安全性而言，迄今為止，我們尚未觀察到使用我們建議的 II 期劑量的該藥物出現嚴重的免疫相關不良事件。劑量擴展隊列正在測試 CD28 加 Libtayo 對 EGFR 的療效，目前已在各種實體瘤中招募患者，包括伴或不伴 EGFR 突變的非小細胞肺癌、微衛星穩定型結直腸癌、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.

接下來是我們的 PSMA by CD28 共刺激雙特異性抗體，該抗體與 Libtayo 聯合使用時，已在晚期前列腺癌治療中顯示出良好的活性。我們現在已經開始將我們的 PSMA 與 CD28 costim 雙特異性抗體和我們的 PSMA 與 CD3 雙特異性抗體進行聯合治療，根據臨床前研究，這可能維持與 Libtayo 聯合治療的療效，並可能改善安全性和耐受性。我們也在其他癌症中測試CD28介導的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的雙特異性抗體。在歐洲血液學協會會議上，我們以口頭報告的形式介紹了 linvoseltamab 或 BCMA by CD3 雙特異性抗體，並展示了更新的關鍵數據，這些數據繼續表明，在療效、安全性、劑量以及住院負擔方面，linvoseltamab 在晚期多發性骨髓瘤治療中具有潛在的同類最佳特性。

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，隨著追蹤時間的延長，回饋意見不斷加深。對 117 名患者進行 14 個月的中位隨訪，50% 的患者達到完全緩解或更佳療效，客觀總體緩解率為 71%。目前，針對骨髓瘤早期階段和前驅疾病（如冒煙型骨髓瘤和意義不明的單克隆丙種球蛋白病或 MGUS）的 linvoseltamab 的進一步研究也在進行中。在早期多發性骨髓瘤治療中開發 linvoseltamab 為我們提供了一個重要的機會，可以幫助患者及其醫生應對這些疾病，因為這些疾病目前的治療模式很複雜。

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.

談談我們的非腫瘤血液學產品線。如前所述，我們預計今年稍後將獲得兩種因子XI抗體在預防膝關節置換術後靜脈血栓栓塞的概念驗證結果。針對因子 XI A2 結構域的抗體研究目前已完成招募，我們預計今年下半年在醫學會議上發表研究結果。

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.

我們針對 XI 因子催化結構域的第二款抗體的 II 期中期試驗結果預計將於今年年底公佈，供內部分析。我們也啟動了一項額外的概念驗證研究，以進一步評估兩種抗體譜在預防週邊置入導管患者血栓形成方面的作用。這些研究的結果將決定明年是否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 受體激動劑可能帶來的負面後果。正如廣泛報導的那樣，這些藥物造成的體重大幅下降，不幸的是，也會導致肌肉大量流失，這尤其令老年肥胖患者擔憂。

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聯合使用，無論是否聯合我們的活性NA抗體，都可能防止這種肌肉流失，正如先前在非人靈長類動物中證明的那樣。我們針對健康受試者測試更高劑量 trevogrumab 或肌肉生長抑制素抗體的 COURAGE II 期研究的 A 部分現已成功完成，未發現新的安全訊號。研究的 B 部分評估了我們的肌肉保護抗體與索瑪魯肽聯合用於肥胖參與者的療效，目前已開始招募患者。假設招募速度合理，我們仍預期在 2025 年下半年公佈主要結果，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.

最後，我將談談我們在基因藥物領域所做的努力。在 ASGCT 會議上，我們展示了我們針對由耳蛋白基因突變引起的遺傳性聽力損失的 DB-OTO 基因治療計畫的最新數據。第一個接受這種療法治療的兒童是一名 11 個月大的女孩，她出生時患有重度耳聾，治療 24 週後聽力恢復正常。此外，在第二個孩子身上也觀察到了初步的聽力改善，該孩子在 4 歲時接受了治療，並在 6 週後進行了評估，並製定了後續隨訪計劃。

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，我們的研究中已有 5 名患者接受了治療，我們預計今年將招募更多患者。我們也期待在未來幾年內將更多的耳蝸蛋白基因治療計畫引入臨床，以期解決更常見的單基因聽力損失問題。關於我們與 Intellia 在轉甲狀腺素蛋白澱粉樣變性伴隨心肌病變方面的合作，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患者，這表明研究人員和患者對此表現出了相當大的興趣。

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，我們有望成為第一個利用 CRISPR 技術在體內插入矯正基因以治療血友病 B 的團隊。如前所述，我們已在該試驗的主要階段招募了首批患者，首位患者應該很快就會接受給藥。我們與 Alnylam 合作開發的 siRNA 不僅成功地沉默了肝臟中的基因，而且首次成功地沉默了大腦中的基因。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攜帶 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階段，包括針對亨廷頓氏症的 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，我們採用的創新方法，即首次將抗體與 siRNA 結合，兩者都靶向同一分子，目前進展順利，我們預計將在今年年底前公佈針對陣發性睡眠性血紅蛋白尿症這一初步潛在適應症的最新數據。

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症的第三階段研究計畫。總而言之，我們將繼續推進創新研發項目，並預計在未來 12 至 18 個月內公佈幾組關鍵性數據和概念驗證數據。我們的早期研究工作持續取得成果，多個創新項目預計將在同一時期進入臨床階段。

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

接下來，我將把電話交給瑪莉安。

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 Regeneron 在各個治療領域的領先地位。我們的業績表明，我們的產品組合持續保持強勁實力和多樣性，現有和即將推出的產品及適應症在多個地區持續推動著成長機會。

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.

我先從美國版的EYLEA HD和EYLEA說起。第二季度，兩種藥品的合併淨銷售額年增2.3%，達到15.3億美元。安永EYLEA HD 持續保持在該類別中的領先地位，同時 EYLEA HD 仍然是這個競爭激烈的類別中成長最快的藥物。EYLEA HD 在第二季持續保持上市勢頭，淨產品銷售額達 3.04 億美元，季增 52%。EYLEA HD 仍然是自十多年前 EYLEA 上市以來，抗 VEGF 療法中上市速度最快的，其發展軌跡證實，向 EYLEA HD 的重大過渡正在進行中。

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 的處方範圍和深度持續擴大，其應用對象涵蓋了廣泛的患者群體，包括未接受過治療的患者群體，該群體自上一季以來翻了一番。根據早期治療的正面效果，醫生也越來越多地將患者從其他抗 VEGF 療法轉為使用 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.

而這些轉用 EYLEA HD 的患者，早期真實世界數據表明，治療間隔正在延長。EYLEA HD 的耐用性，以及與 EYLEA 相同的可靠療效、視力和安全性，代表著對患者生活的重要改善和對醫生診療效率的顯著提高。

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。我們認為這表明處方醫生對 EYLEA HD 的臨床表現以及報銷情況充滿信心，因為永久性 J 代碼已經充分確立。

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充式註射器選擇的重要性，正如 Len 所提到的，我們對即將推出的 EYLEA HD 預充式註射器感到非常興奮。總而言之，我們對 EYLEA HD 和 EYLEA 第二季的表現感到滿意，並繼續朝著將 EYLEA HD 確立為視網膜疾病新標準的目標穩步前進。

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.

緊隨其後的是 Dupixent，該公司第二季以固定匯率計算成長了 29%，全球淨銷售額為 35.6 億美元。我們即將迎來一個重要的里程碑，全球使用 Dupixent 的患者人數已達 100 萬人。此外，由於在適應症、年齡和地理方面存在巨大的未滿足需求，Dupixent 還有很大的機會讓更多患者受益。

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，淨銷售額成長了 24%，達到 26.1 億美元，這主要得益於所有五種核准適應症的需求增加。Dupixent 繼續保持其市場領先地位，並在所有核准適應症中保持著新藥處方量第一的地位。我們的商業團隊將繼續全力以赴，推動各項舉措，以提高患者意識並支持處方行為。我們持續看到，在異位性皮膚炎、氣喘和鼻息肉等重磅適應症領域，我們的藥物滲透率不斷提高。

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，最近在嗜酸性食道炎和結節性癢疹方面的上市情況超出了我們的預期，新患者的起始治療數量也穩定增加。我們聽說了一些令人矚目的故事，一些年僅一歲的嗜酸性粒細胞性食道炎 (EoE) 患者，在今年 1 月 Dupixent 獲批後，現在都已康復。

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了 Dupixent 用於治療血液嗜酸性粒細胞增多的 COPD 患者，德國的患者已經開始接受治療。我們都認識到，全球範圍內患有這種衰弱性疾病的患者存在著巨大的未滿足需求，而 Dupixent 是第一個用於治療 COPD 的生物製劑。我們的美國團隊已做好準備，迎接 FDA 預計在 9 月底批准 Dupixent 用於治療 COPD，並估計大約有 30 萬美國患者可能會從 Dupixent 的這種適應症中受益。此外，FDA 預計將於下個月對 Dupixent 用於治療青少年慢性鼻竇炎和鼻息肉做出決定。

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.

正如喬治所提到的，Dupixent 的兩個 III 期臨床試驗計畫將於今年稍後公佈結果，分別針對慢性自發性蕁麻疹和大皰性類天皰瘡。如果這些試驗的數據是正面的，Dupixent 有可能幫助更多未滿足醫療需求的患者。第二季度，Libtayo 也取得了重大進展，全球淨銷售額達 2.97 億美元，以固定匯率計算年增 43%。強而有力的商業執行使公司在皮膚癌和肺癌市場都獲得了市場份額。

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，淨銷售額成長了 40%，達到 1.82 億美元，所有市場領域和適應症都成長。在非黑色素瘤皮膚癌領域，隨著需求和市場份額的不斷增長，我們繼續擴大 Libtayo 的領先地位。在肺癌領域，利必妥被醫生們公認為肺癌患者的重要療法，並持續逐步擴大市場份額。在美國以外，我們的團隊取得了優異的成績，淨產品銷售額達到 1.15 億美元，Regeneron 繼續推進其國際擴張。Libtayo 在部分國際市場的淨產品銷售額因約 1500 萬美元的庫存採購而受到有利影響。

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.

我們的腫瘤科團隊也熱切期盼美國食品藥物管理局 (FDA) 和歐盟對 linvoseltamab 用於治療晚期多發性骨髓瘤的潛在決定。我們相信 linvoseltamab 代表著同類最佳的機會，我們期待它未來的上市。總而言之，我們的商業團隊繼續朝著我們的目標邁進，即為全球更多患者提供 Regeneron 的藥物。在已核准的適應症範圍內，未來具有巨大的成長潛力；我們強大的產品線為推進病患照護提供了近期和長期的機會。

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

接下來，我將把電話交給克里斯。

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，瑪莉安。除非另有說明，我今天對 Regeneron 的財務業績和展望的評論將以非 GAAP 準則為基礎。再生元公司第二季營收和利潤均實現了強勁的兩位數成長。

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% 至 35 億美元，主要得益於 EYLEA HD 在美國持續強勁的上市、賽諾菲合作收入的增加以及 Libtayo 全球銷售的持續成長。第二季稀釋後每股淨收益較上年同期成長 13%，達到 11.56 美元，淨收益為 14 億美元。第二季度，我們與賽諾菲的合作收入成長至 11 億美元，主要包括我們應得的合作利潤 9.88 億美元，較上年同期成長 32%，這主要得益於 Dupixent 銷量持續成長和利潤率提高。

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.

賽諾菲合作收入的另一組成部分——生產和商業供應的報銷額為 1.57 億美元。考慮到銷售量增加，但生產效率提高，我們仍然預計 2024 年生產和商業供應的報銷額將與 2023 年全年水準相當。截至第二季末，賽諾菲的研發資金餘額約為 20 億美元，比第一季末減少了約 1.9 億美元。我們仍預計到 2026 年底，賽諾菲將全額償還這筆款項。

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.

加入拜耳公司。第二季度除美國以外，EYLEA 和 EYLEA 8 毫克的淨銷售額為 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.

接下來是我們的營運費用。第二季研發支出年增 10% 至 11 億美元，反映出我們為支持強大的研發管線（包括後期腫瘤學和血液學計畫）而持續進行的投資。我們將繼續進行深思熟慮的投資，以便能夠迅速進入 III 期項目，預計在未來 12 至 18 個月內將獲得數據讀數支持這一目標。

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.

第二季銷售、一般及行政費用較上年同期成長 19%，達到 6.66 億美元，主要原因是為支持 EYLEA HD 的上市以及我們持續的國際商業擴張而進行的投資。第二季毛利率和淨產品銷售額約為 89%，這反映了我們灌裝/包裝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.

接下來我們來看現金流量表和資產負債表。再生元公司在 2024 年上半年產生了約 16 億美元的自由現金流，並在季度末持有現金和有價證券減去債務後約 148 億美元。今年上半年，我們回購了約 9 億美元的股票，截至第二季末，我們約有 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 年全年財務預期進行了一些細微的調整。我們更新了 2024 年毛利率預期，目前預計毛利率約為 89%，主要反映了產品組合的預期變化以及更高的非產品特定成本，包括灌裝/包裝設施的啟動成本。我們最新的全年業績預期完整摘要已發佈在今天早上早些時候的新聞稿中。總而言之，Regeneron 在第二季度取得了優異的業績，並已做好充分準備，在短期和長期內繼續推動成長。

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

這樣，我就把電話轉回給瑞恩了。

Thank you, Chris. This concludes our prepared remarks. We will now open the call for Q&A. 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。我們的發言稿到此結束。現在開始問答環節。為了確保我們能夠解答盡可能多的問題，我們將在回答每位來電者的一個問題後再進行下一位來電者的問題。香農，我們能直接進入第一個問題嗎？

(Operator Instructions) Tyler Van Buren, TD Cowen.

（操作說明）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?

嘿，夥計們。早安.恭喜你們本季取得佳績。關於愛麗 (EYLEA) 系列產品，我非常欣慰地看到該系列產品的整體銷量同比增長，並且 45% 的品類份額環比保持穩定。那麼，您認為EYLEA HD的上市是否已經達到一定階段和成熟度，從而使其在整個品類中的份額在未來幾個季度保持相對穩定，使您能夠參與到視網膜疾病市場的增長中來？該市場目前是否仍以每年約10%的速度成長？

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，那我分幾次接受吧。謝謝你的提問。首先，我想說的是，我們非常高興地宣布，本季淨銷售額總計達到 14 億美元——抱歉，是 15.4 億美元。正如您所提到的，這比去年同期增長了 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，我再簡單評論一下 EYLEA HD。我們目前確實還處於啟動階段。這是我們今天公佈的第三個完整季度業績。當然，令人鼓舞的是，本季淨銷售額成長了 52%。當然，這一數字意味著淨銷售額比上一季增加了 1 億美元，這在競爭激烈的市場中是非常可觀的。

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.

所以，我們當然會繼續推進產品發布，並且認為這非常重要。當然，EYLEA 是 EYLEA HD 的重要轉診病患來源。接下來，我們看到來自 faricimab 和 Avastin 的轉換，本季度我們也非常高興地報告，我們在初治患者群體中看到了 EYLEA HD 的使用增加。總而言之，我們認為這表明 EYLEA HD 有潛力成為新的護理標準，並且肯定具備這樣的實力。

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。我也來介紹一下這方面。我認為，就今年這個階段而言，我們追蹤到的中檔品類成長更多是個位數，而不是兩位數，而我認為這正是你在問題中提到的。

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，瑪莉安。我們進入下一個問題吧。

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。非常感謝您回答我的問題，也一直祝賀您的進步。我想談談您在肥胖症領域，特別是瘦素的研究工作。您能否簡要解釋一下將該專案推進到第二階段的理由？我知道瘦素一直備受爭議。顯然，你在先前的試驗中看到了一些有趣的數據。但是，為什麼要在例如替拉帕肽的基礎上再添加這種藥物，而不是使用禮來公司正在進行的其他一些試驗中使用的三重激動劑呢？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，我們接下來會在很多不同的項目中引入瘦素。我相信你指的是與其他減肥藥併用的那種。這是基於以下結果得出的結論：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實際上正處於肥胖加劇階段的患者中，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.

它們已經飽和了。一旦你體重大幅下降，瘦素水平就會下降，你可能會進入瘦素發出信號的範圍，這會使個體對食物的渴望增加。因此，對於這些患者來說，體重減輕可能受到瘦素減少的限制，而瘦素減少又會促使他們增加進食行為。

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.

所以這可能是，而且至少在動物研究中已經表明，瘦素可能確實在這種情況下發揮重要作用。正如你所指出的，在對病情穩定的肥胖患者的歷史研究中，瘦素已經飽和，給予更多瘦素可能不會帶來益處。但在這些瘦素水平下降的情況下，瘦素水平的下降和低水平可能會導致覓食衝動，在這種情況下給予瘦素可能會在其他藥物所獲得的減肥效果的基礎上進一步減輕體重，而其他藥物的減肥效果往往會在某個階段達到平台期，至少根據動物研究，這種平台期可能部分是由瘦素的下降所驅動的。如您所知，這些研究是與禮來公司合作進行的。所以，我們正在與他們的藥物替拉帕肽合作研究它。

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

謝謝你，喬治。我們來看下一個問題。

Brian Abrahams, RBC Capital Markets.

Brian Abrahams，加拿大皇家銀行資本市場。

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.

嘿，早安。感謝您回答我的問題，並祝賀您本季的成就和所有進展。關於 linvo，在您準備在那裡的潛在上市之際，我很好奇您收到的反饋，醫生們可能會如何看待它與現有療法的相對關係，以及人們對您在幻燈片中提到的療效和給藥優勢的認可程度如何？或許您也可以再詳細說明第三方設施的一些問題，他們也很有信心這些問題能夠解決。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.

我將負責第三方問題，喬治或瑪麗昂可以負責，討論人們如何看待BCMA方法以及它在長期發展中可能扮演的角色。在我們整個生物製藥領域，第三方填充劑類型和製造方面存在許多問題，並出現了大量的 CRL（完整報告清單）。

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 有過類似事件，當時 FDA 正在檢查我們用於其他產品的填充劑。他們發現了一些需要整改的情況，但由於這些問題的性質，我們認為有必要進行複查，因為我們得到的消息是這些問題已經得到整改。但由於需要重新檢查，所以可能無法完成，很可能無法在我們的 PDUFA 日期之前完成。這就是我們提醒你注意這一點的原因。

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.

這是一個行業普遍存在的問題。我認為美國食品藥物管理局（FDA）實際上正在計劃就此類事項舉行一些公開聽證會。我們正在與FDA合作，因為這是優先審查申請，目的是看看我們如何以最快的速度解決這個問題。

George or Marion, do you want to cover these?

喬治還是瑪莉昂，你們想負責這些？

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，然後交給瑪莉安。但正如我們總結和詳細介紹的，並且我們將繼續展示的那樣，隨著數據的成熟和患者的持續治療，我們的雙特異性抗體的療效數據繼續保持領先地位，他們的反應也越來越深，目前我們的完全緩解率達到 50%，我們相信，我們的 PFS 和總生存期數據也是同類最佳的。

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努力消除癌症，並使患者獲得長期持久的療效和存活期。我們認為這正是病人和醫生所關注的重點。我們相信，就安全性、給藥方案和住院負擔而言，我們的產品在其他方面也是一流的。至於馬里恩認為醫生群對這些數據的看法，我會請馬里恩對此發表評論。

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.

謝謝你，喬治。當然，我們對linvoseltamab可能即將獲得批准感到非常興奮。George 描述了差異化的臨床療效和安全性，這對醫生來說極為重要。我們擁有一支經驗豐富的血液科團隊，隨時準備啟動專案。

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，我還要補充一點，這位是Len。我還要補充一點，顯然，我們不會只限於最後一行。我們正積極嘗試以單藥療法或合併療法的方式，將這種療法推廣到更多早期治療方案。

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.

癌症治療的經驗法則是，越早進行治療，往往能獲得越多的療效。但考慮到喬治剛才跟你說的我們在上一行看到的回覆數量，這將會非常了不起。所以我們對推進這項工作感到非常興奮，我們會繼續努力——我們會隨時向您報告最新進展。

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，我只是想補充一下 Len 剛才說的，這就是為什麼我們要在這些早期療法中進行這些試驗的原因。顯然，在獲得臨床試驗結果之前，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.

好的，先生們。我們來看下一個問題。

Cory Kasimov, Evercore ISI.

Cory Kasimov，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.

謝謝大家。早安.感謝您回答這個問題。因此，我們收到了越來越多關於貴公司 Factor XI 專案的諮詢。您能否談談您提供的兩種抗體之間，可能對喬治來說，有哪些不同之處？那麼，在接下來的報告撰寫過程中，您將重點放在哪些關鍵方面，以確保您走在正確的道路上？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。所以非常重要的是，我們創造出了能夠破壞其作用機制的抗體。一個影響活化結構域，另一個影響催化結構域。我們在這兩類抗體中都開發出了同類中唯一或同類最佳的抗體，這些抗體能夠根據所有跡象，最有效地擊中並抑制目標，並結合大量的遺傳學研究（部分得益於我們自己的 Regeneron 遺傳學研究等等），這表明這兩種方法將使我們能夠分離並優化最佳療效和最佳安全性。

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，我們很有可能會針對不同的目標族群推進這兩種抗體的研發，其中一些族群的療效是主要驅動因素，而有些族群的安全性可能是最重要的。所以它們的作用機制非常獨特。他們確實在探索這個靶點，不僅透過分解作用機制更加精確，而且比競爭對手的抗體更強大，因為競爭對手的抗體只能做到其中一項或兩項。

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.

所以我們對這些項目感到非常興奮。正如我們所說，我們正在進行一些概念驗證研究，我們希望到今年年底能夠宣布我們未來可能會對這兩種抗體採取何種方向。

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

謝謝你，喬治。香農，我們進入下一個問題吧。

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。還有一個關於安永及其商業進展的小問題。所以我覺得你們在永久 J 代碼的聲明中已經非常明確了，我們不應該看到像 VABYSMO 獲得永久 J 代碼時那樣的轉折，因為當時還有一些其他變量，例如折扣等等。

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.

但我們收到了一些市場回饋，即使 J 代碼發生了變化，仍然存在准入障礙，尤其是在 Medicare Advantage 計劃中。Marion，我很好奇你是否可以談談那裡的動態，以及你認為在永久 J 程式碼之後，存取權限方面的事情會如何發展。

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。我非常非常樂意發表評論。因此，對於一部分市場，即按服務收費的聯邦醫療保險患者來說，醫生享有開放的准入和處方自由。如果我們進入那些受支付方影響的市場領域，我們的團隊已經成功地為 EYLEA HD 開闢了准入途徑，覆蓋了超過 80% 的患者群體。

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，我們確實取得了重大進展，我們將繼續努力解決醫生可能遇到的一些利用管理或階梯式編輯問題。我想說的是，當醫生和辦公室工作人員提供資訊時，這些問題通常很容易解決。但總的來說，最重要的訊息是 EYLEA HD 的醫療覆蓋範圍非常廣。而且，在已實施報銷的市場中，80% 的市佔率都得到了覆蓋。

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

謝謝你，瑪莉安。香農，我們來看下一個問題吧。

Akash Tewari, Jefferies

阿卡什‧特瓦里，傑富瑞集團

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。這裡是凱西，替阿卡什報道。那麼，關於您的肌肉生長抑制素項目，您能否談談您在 III 期試驗中更傾向於使用雙藥聯合療法還是三藥聯合療法？另外，您認為肌肉生長抑制素與 GIP、GLP、胰淀素合併療法相比會如何？這些療法可能顯示 90% 以上的脂肪與肌肉減少效果。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。嗯，我們再次強調，我們關注的是創建能夠讓我們更好地剖析該通路並分離出最重要的參與者的單一試劑。如您所知，例如，其他人正在使用一種抗體，該抗體可以阻斷所有通路，不僅是我們所針對的兩條通路，還有大約 20 條與肌肉無關的其他通路，我們知道這些通路已知會產生各種其他潛在的副作用和不良反應。

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，我們針對該機制中的兩條肌肉特異性路徑進行了研究。我們想看到的是，哪種藥物在療效和安全性方面表現最佳，我們認為這一點非常重要。一旦我們確定了這一點，我們就可以推進將這兩種抗體中的一種或兩種與減肥藥結合使用，或者我們還在研發管線中開發各種單分子解決方案，使單個分子能夠攻擊我們想要攻擊的多個通路中的任何一個，以及減肥通路。

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，我們希望透過盡可能精確、科學地剖析該途徑，從而使我們能夠從可以採取的單分子解決方案中進行選擇。也就是說，請記住，這不僅僅是增加減肥效果的問題，因為隨著減肥效果的增強，無論你使用哪種途徑，你都可以使用 GLP-1 激動劑、GPR 拮抗劑，還可以添加其他途徑。肌肉萎縮越嚴重，發生得越快，這正是患者所希望的，因為這是必要的，因為你要模擬飢餓狀態來激活該通路，這必然會導致肌肉萎縮，原因就在於激活了我們正在研究的這些通路。

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，目前任何以快速減重為目標的減重方法，由於其依賴進化上保守的途徑，必然會導致嚴重的瘦身和肌肉流失，這對患者，尤其是老年肥胖患者，會造成巨大的損害。透過引入這些阻斷這些特定路徑的代理人，我們或許能夠做到兩件事。我們或許可以阻止伴隨快速而劇烈的體重減輕而來的、必然在進化過程中保留的肌肉流失，同時或許還能增加脂肪的減少量，而這正是你想要減掉的。

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.

這就是我們目前在臨床前研究中，包括透過非人靈長類動物研究所證明的，而我們現在正在進行的這些研究應該能夠告訴我們，所有這些在進化上高度保守的途徑是否真的適用於人類，以及我們是否真的能夠優化減重（這並不重要），尤其是在保持肌肉的同時優化減脂。我們相信，只有我們才能真正精確地探究這些路徑，並且能夠剖析它們，從而確定哪條路徑才是最佳、最安全的，能夠為患者帶來最大的益處。

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

好的。謝謝你，喬治。香農，請問下一個問題。

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。非常感謝你的提問。僅涉及linvo、Dupixent和食物過敏。我知道現在說這些還為時過早，但這確實是一個令人興奮的項目。您能否幫我們估算一下，如果今年稍後以及未來一段時間我們看到的數據支持推進這種聯合療法，那麼您認為這種療法可能適用於多少食物過敏患者或患者百分比？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.

我認為這最終還是要回到收益與風險比的問題。正如我在其他節目中所說，這正是我們關注的重點。根據我們展示的所有數據，我們相信，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細胞，然後透過給予世界上歷史上最安全的生物製劑之一——Dupixent，來非常安全地防止它們復發。當然，這還需要在患者身上得到驗證。

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，我們先從最嚴重的食物過敏患者開始。對於這些患者，例如，他們有非常高的未滿足需求、非常高的風險等等，因此有必要採取這種方法。它的效果越好，更重要的是，我們越能證明它的安全性，那麼它的適用範圍就能越廣。事實上，如果最終我們真的找到了一種非常安全的方法來消除所有致敏細胞，並防止它們反彈。

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.

尤其需要記住的是，這些患者中的大多數還患有其他過敏性疾病，其中一些患者可能已經適合使用 Dupixent。所以你給他們服用的藥物可能確實對他們有幫助，而且就幾乎所有生物製劑而言，這種藥物已被證明相當安全。我們或許可以接診病情較輕的過敏患者。因此，我們可以從目前遇到的最嚴重的患者入手，這些患者的需求未得到充分滿足，我們需要研究這種方法是否有效，以及是否安全，以及它的安全性如何。越安全，我們就可以逐步擴大研究範圍。

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.

最終也不必局限於食物過敏，實際上可以消除幾乎所有過敏症，從最嚴重的到最普通的，但這取決於益處、風險和安全性，而這正是我們在這些初步研究中測試的內容。對於初步研究，我們選取了食物過敏最嚴重的患者，他們有很高的未滿足需求和很高的風險狀況。根據研究進展，我們可以將研究範圍擴大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。如果只看每年急診室就診人數，就會發現可能有數十億人因食物過敏而去急診室。顯然，實際發生過敏性休克的人數較少。

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.

但正如喬治所說，如果只需要在BCMA中進行誘導治療就能啟動服用杜匹洛韋的過程，那麼杜匹洛韋是一種非常安全的藥物，我們有數十萬，接近數百萬的患者正在服用這種藥物。所以我們知道了這種藥物的特性。所以這一切都符合科學原理。我們只需要慢慢來，穩健行事，看看結果如何。

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

謝謝Len和George。我們進入下一個問題吧。

Tim Anderson, Wolfe Research.

提姆·安德森，沃爾夫研究公司。

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。我有一個關於安禮集團的問題，以及司法部自四月以來對安禮集團行銷行為的調查，他們聲稱安禮集團違反了《虛假申報法》。您能否提供一下接下來的發展？特別是在此期間，出於謹慎考慮，Regeneron 自 4 月以來是否改變了任何行銷策略？這是否對處方醫生產生了任何影響？我這麼問是因為在第 6 張幻燈片中，你提到了其他導致銷售下降和價格下跌的市場動態。我只是好奇那些是什麼。

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產品。坦白說，我們認為這場訴訟毫無根據。我們沒有改變做法，打算堅決與之抗爭。我想，一旦你看到我們在法庭上的文件，你會對此有更深刻的理解。

David Risinger, Leerink Partners

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。所以 Regeneron 顯然是一家非常優秀的研發領導者，但公司外部也發生了大量的創新，而且該公司擁有雄厚的資產負債表，卻沒有真正加以利用。所以我的問題是，是否有可能透過收購治療嚴重眼疾的新型潛在重磅療法來利用 Regeneron 在眼科疾病領域的商業優勢？如果屬實，該公司是否認為在近期到中期內有任何機會這樣做？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到的問題。我們是否應該努力爭取一些並非源自於我們自身創新的機會？我們從未見過如此大規模的事件。顯然，我們已經進行了一些小規模的測試，數量從幾億到幾百萬不等。至於我們是否可以利用我們現有的產品或研發能力，這當然是我們正在考慮的事情，但目前對於後期產品，我們還沒有看到任何機會。

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

謝謝你，Len。香農，我們進入下一個問題吧。

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.謝謝您回答我的問題。關於這裡的 Factor XI 項目，您能否談談其中蘊含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.

正如我所說，我們目前正處於評估針對因子 XI 的兩類抗體的階段，這兩類抗體以兩種不同的方式攻擊該路徑。我想我們已經討論過了。其中一種藥物在預防血栓形成方面更有效，但可能伴隨更嚴重的副作用。另一種方法可能效果稍差，但安全性較高。

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，我們認為使用攻擊兩個不同部位的兩種抗體來精確地研究這條路徑非常重要。這是其中一種酵素。它具有活化結構域和催化結構域。透過分別阻斷這兩個不同的結構域，我們期望能夠提供兩種不同的方案，每種方案都包含一流的抗體。

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特徵，我們就能知道在抗體研發方面，我們應該朝哪個方向發展，或者兩者兼而有之。我們可以很容易地想像，對於風險較高的患者，比如說，將療效較差的藥物引入到更注重安全性和預防血栓不太重要的環境中。所以這一切都將取決於這些個人資料。

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前獲得關鍵數據，這將更好地確定它們的療效和安全性，以及它們與目前市面上各種現有藥物的比較情況，並確定它們在哪些適應症上的應用方向。因此，我們希望透過初步的概念驗證研究，更了解兩種抗體及其兩種不同的特性。

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.

然後，我們就能知道該如何引導他們，以及最終的機會是什麼。但顯然，這裡仍然非常需要能夠阻止、凝固和血栓形成的藥物。安全性能在這裡至關重要，我們非常高興有機會擁有這兩個密切相關但截然不同的性能指標。

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.

我再補充一下喬治所說的，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。如果你能為部分、大部分或某個細分市場帶來類似的療效，但安全性更高，那麼你就真的擁有了一個巨大的機會。所以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.

在合適的條件下，我們能否使用其中一種或另一種抗體來實現治療？正如喬治所建議的那樣，這兩種抗體可以達到相同或更好的療效，但安全性更高。如果我們能做到這一點，如果我們能為患者做到這一點，那麼我們將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，由於安全狀況的原因，您不會使用某些代理，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，我們進入下一個問題吧。

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.恭喜你本季取得佳績。我讚賞 Len 先前對預充式註射器工作的評論，但對於 Marion 和她的團隊來說，更重要的是確保高劑量上市的勢頭不會因為 VABYSMO 使用預充式註射器在短期內相對不利而受到影響。如果您能更具體地說明您的時間表，那就太好了。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.

嗯，我想我在準備好的演講稿中說過，我們預計將於 2025 年初發布。我不確定競爭對手究竟會如何發布產品，但我認為，如果他們比我們先發布，我們大概也就落後幾個月而已。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特性、藥物的持久性以及他們使用活性成分阿柏西普的安全經驗。因此，我們對正在進行的發布會感到非常有信心。

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

謝謝。香農，我們還有時間再問兩個問題。

Terence Flynn, Morgan Stanley.

Terence Flynn，摩根士丹利。

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。這裡是克里斯替特倫斯報道。我們只有一個關於EYLEA HD的問題。鑑於您在第二季所看到的市場動態。我們該如何看待 2024 年下半年的轉換速度？

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

你該好好考慮一下。那是你的工作。我不知道瑪麗昂是否想對此發表任何評論。

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，正如我之前所說，我們對 EYLEA HD 的發布進度非常滿意。

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

好的。謝謝。香農，我們來問最後一個問題。

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?

香農，非常感謝你回答我的問題。我只想再談談 EYLEA HD。瑪麗昂，就目前而言，轉換治療和未經治療的患者之間的適應程度分別是多少？我猜他們大多都是轉換型糖尿病患者，而且在初期治療這類患者是否比較困難？

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.

那麼，展望未來，你認為你現在還處於轉型初期嗎？或者，您認為在建立 EYLEA HD 與標準劑量 EYLEA 的模型時，從定價和獲取途徑的角度來看，我們還應該考慮哪些其他因素？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.

所以，對於 EYLEA HD 患者來說，總是包括轉診患者和初次接受治療的患者。今天我提到了將患者轉用 EYLEA HD 的情況，這非常令人鼓舞，這並不奇怪，因為 EYLEA 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.

第三類轉診患者來源是阿瓦斯汀，然後還有其他所有藥物。但正如我在本季報告中提到的，真正令人鼓舞的是，未接受過治療的患者的使用率比上一季翻了一番。因此，我們將繼續看到持續的組合，就像每個產品一樣，如果它在該類別中具有合適的特性，但 EYLEA HD 的處方發展進展非常順利。

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.

謝謝瑪麗昂，也謝謝今天所有撥入電話對 Regeneron 有興趣的朋友。對於那些仍在問答隊列中但沒有機會發言的人，我們深表歉意——我們沒能聽到他們的意見。如有任何疑問，投資人關係團隊隨時為您解答。再次感謝，祝您今天過得愉快。

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了。