雷傑納榮製藥 (REGN) 2023 Q2 法說會逐字稿

Welcome to the Regeneron Pharmaceuticals Second Quarter 2023 Earnings Conference Call. My name is Shannon, and I will be your operator for today's call. (Operator Instructions) Please note that this conference is being recorded. I will now turn the call over to Ryan Crowe, Vice President, Investor Relations. You may begin.

歡迎參加再生元製藥 2023 年第二季度收益電話會議。我叫香農，我是今天電話的接線員。 （操作員說明）請注意，本次會議正在錄製中。我現在將把電話轉給投資者關係副總裁 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 2023 earnings conference call.

謝謝你，香農。世界各地的聽眾早上好、下午好、晚上好。感謝您對 Regeneron 的關注，歡迎參加我們的 2023 年第二季度收益電話會議。

An archive of this webcast will be available on our Investor Relations website shortly Shortly after the call ends. Joining me on today's call are Dr. Leonard Schleifer, Board Co-Chair, Co-Founder, President and Chief Executive Officer; Dr. George Yancopoulos, Board Co-Chair, Co-Founder, President and Chief Scientific Officer; Marion McCourt, Executive Vice President and Head of Commercial; and Bob Landry, Executive Vice President and Chief Financial Officer. After our prepared remarks, we will open the call for Q&A.

通話結束後不久，我們的投資者關係網站將提供該網絡廣播的存檔。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、聯合創始人、總裁兼首席科學官； Marion McCourt，執行副總裁兼商務主管；和鮑勃·蘭德里，執行副總裁兼首席財務官。在我們準備好發言後，我們將開始問答環節。

I would like to remind you that remarks made on today's call may include forward-looking statements of Regeneron. Such statements may include, but are not limited to, those related to Regeneron and its products and business, financial forecast and guidance, revenue diversification, development programs and related anticipated milestones including anticipated regulatory actions, collaborations, finances, regulatory matters, payer coverage and reimbursement issues, intellectual property, pending litigation and other proceedings and competition.

我想提醒您，今天電話會議上的言論可能包括再生元的前瞻性陳述。此類聲明可能包括但不限於與再生元及其產品和業務、財務預測和指導、收入多元化、開發計劃和相關預期里程碑相關的聲明，包括預期監管行動、合作、財務、監管事項、付款人覆蓋範圍和報銷問題、知識產權、未決訴訟和其他訴訟和競爭。

Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-Q for the quarterly period ended June 30, 2023, 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.

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存在重大差異。有關這些風險和其他重大風險的更完整描述可以在 Regeneron 向美國證券交易委員會提交的文件中找到，其中包括今天上午向 SEC 提交的截至 2023 年 6 月 30 日的季度期間的 10-Q 表。再生元不承擔任何更新任何前瞻性陳述的義務，無論是由於新信息、未來事件還是其他原因。

In addition, please note that GAAP and non-GAAP measures will be discussed in today's call. Information regarding our use of non-GAAP financial mesures and a reconciliation of those measures to GAAP is available in our financial results press release and our corporate presentation, which can be accessed on our website. Once our call concludes. Rob Landry and the The IR team will be available to answer further questions. With that, let me turn the call over to our President and Chief Executive Officer, Dr. Len Schleifer. Len?

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措施。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，請參閱我們的財務業績新聞稿和公司演示文稿，這些信息可以在我們的網站上訪問。一旦我們的通話結束。 Rob Landry 和 IR 團隊將可以回答進一步的問題。接下來，讓我將電話轉給我們的總裁兼首席執行官 Len Schleifer 博士。萊恩？

Thanks, Ryan, and thanks to everyone joining today's call. Regeneron delivered strong results across the organization in the second quarter of 2023 while continuing to make progress toward our long-term objective of growing the business while simultaneously diversifying it's revenue and earnings streams.

謝謝瑞安，也感謝參加今天電話會議的所有人。 Regeneron 在 2023 年第二季度在整個組織中取得了強勁的業績，同時繼續朝著我們發展業務的長期目標取得進展，同時實現收入和收益流多元化。

Total revenues increased by 11% compared to the prior year quarter, primarily driven by Sanofi collaboration revenues and Libtayo net product sales, which grew by 39% and 49%, respectively.

總收入較上年同期增長 11%，主要由賽諾菲合作收入和 Libtayo 淨產品銷售額分別增長 39% 和 49% 推動。

Non-EYLEA revenue contributions were 41% of total revenues. The highest proportion for any quarter in the last 10 years, excluding those with COVID antibody revenue contributions. Overall, we were pleased with the trajectory of the business and believe the company continues to be well positioned to deliver long-term growth.

非 EYLEA 收入貢獻佔總收入的 41%。不包括新冠抗體收入貢獻的季度，這是過去 10 年來任何季度的最高比例。總體而言，我們對公司的業務發展軌跡感到滿意，並相信公司將繼續處於有利位置以實現長期增長。

In a few minutes, George, Marion and Bob will provide commentary on pipeline developments, commercial execution and financial results that we achieved during the second quarter. For the remainder of my remarks today, I will focus on aflibercept 8 milligrams.

幾分鐘後，喬治、馬里昂和鮑勃將對我們第二季度取得的管道開發、商業執行和財務業績發表評論。在今天剩餘的發言中，我將重點討論阿柏西普 8 毫克。

We are very excited about the emerging clinical profile including the compelling 2-year data from the pivotal PHOTON study in patients with diabetic macular edema, which George will discuss in more detail.

我們對新興的臨床概況感到非常興奮，包括來自針對糖尿病性黃斑水腫患者的關鍵 PHOTON 研究的令人信服的 2 年數據，喬治將更詳細地討論這些數據。

Now I will summarize the progress that has been made toward getting this important product candidate approved by the FDA. As we announced in late June, the Complete Response Letter, or CRL, that we received from the FDA regarding our biologic license application for aflibercept 8 milligrams for the treatment of patients with wet age-related macular degeneration, DME and diabetic retinopathy did not identify any issues related to aflibercept 8 milligrams clinical efficacy, safety profile, trial design, labeling or drug substance manufacturing nor has the FDA requested any additional clinical data.

現在我將總結這一重要候選產品獲得 FDA 批准所取得的進展。正如我們在6 月下旬宣布的那樣，我們從FDA 收到的關於我們申請阿柏西普8 毫克用於治療濕性年齡相關性黃斑變性、DME 和糖尿病視網膜病變患者的生物製品許可申請的完整回复函(CRL) 並未明確與阿柏西普 8 毫克臨床療效、安全性、試驗設計、標籤或原料藥製造相關的任何問題，FDA 也沒有要求任何額外的臨床數據。

The CRL was entirely based on unresolved observations resulting from the May 2023 FDA pre-approval inspection of a third-party contract manufacturing organization, Catalent that we generally engaged to complete vial filling for aflibercept 8 milligrams. The inspection observations were noted in a Form 483 and were related to a manufacturing line in Catalent's facility that is used to fill vials with the aflibercept 8 milligrams as well as our C5 antibody, pozelimab, for the ultrarare chapel disease, which has a PDUFA date of August 20.

CRL 完全基於2023 年5 月FDA 對第三方合同製造組織康泰倫特(Catalent) 進行預批准檢查時產生的未解決的觀察結果，我們通常聘請該組織來完成阿柏西普8 毫克的小瓶灌裝。檢查結果記錄在表格483 中，與Catalent 工廠的一條生產線相關，該生產線用於向小瓶中灌裝8 毫克阿柏西普以及我們的C5 抗體pozelimab，用於治療極其罕見的教堂疾病，該疾病有PDUFA 日期8 月 20 日。

The inspection was conducted as part of the FDA review process for both the aflibercept 8-milligram BLA and the pozelimab BLA. Broadly speaking, the observations cited production and process control procedures, equipment validation and facility maintenance.

此次檢查是 FDA 對阿柏西普 8 毫克 BLA 和 pozelimab BLA 審查過程的一部分。從廣義上講，觀察結果引用了生產和過程控製程序、設備驗證和設施維護。

We, Catalent and the FDA have had multiple discussions since the aflibercept 8-milligram CRL. There is a clear understanding of the remediation work that is required to allow the FDA to resume approving BLAs that involve manufacturing on this line. Catalent has already provided data and information to the FDA that could satisfy some of these requirements and expect to be able to provide the remaining required data and information by mid-August.

自阿柏西普 8 毫克 CRL 推出以來，我們、康泰倫特和 FDA 進行了多次討論。對於 FDA 恢復批准涉及該生產線生產的 BLA 所需的補救工作有了明確的了解。 Catalent 已經向 FDA 提供了可以滿足其中一些要求的數據和信息，並預計能夠在 8 月中旬之前提供其餘所需的數據和信息。

The FDA said they will strive to complete their review expeditiously prior to the August 20 PDUFA date for pozelimab. However, if they are unable to complete their review before this date, the FDA said that they may need to extend their review by up to 3 months.

FDA 表示，他們將努力在 8 月 20 日 PDUFA 日期之前迅速完成對 pozelimab 的審查。然而，如果他們無法在此日期之前完成審查，FDA 表示他們可能需要將審查時間延長最多 3 個月。

If they do extend the review, FDA has stated that they will continue to prioritize the review and complete it as early as possible.

FDA 表示，如果他們確實延長審查，他們將繼續優先考慮並儘早完成審查。

Importantly, the FDA has also stated that their review of the Catalent manufacturing data in the context of the pozelimab BLA will support actions for both the pozelimab BLA and the aflibercept 8-milligram BLA resubmission, which has already been submitted. In summary, we and Catalent expect to submit by mid-August, all of the Catalent manufacturing data and information required to address the observations resulting from the pre-approval inspection.

重要的是，FDA 還表示，他們在 pozelimab BLA 背景下對康泰倫特生產數據的審查將支持 pozelimab BLA 和已經提交的阿柏西普 8 毫克 BLA 重新提交的行動。總之，我們和康泰倫特預計在 8 月中旬之前提交所有康泰倫特製造數據和信息，以解決預批准檢查中發現的問題。

The FDA has stated that they will strive to complete their review expeditiously prior to August 20. If not, we anticipate the FDA will act on pozelimab and aflibercept 8-milligram BLAs before the end of the third quarter.

FDA 表示，他們將努力在 8 月 20 日之前迅速完成審查。如果不能，我們預計 FDA 將在第三季度末之前對 pozelimab 和 aflibercept 8 毫克 BLA 採取行動。

In closing, we remain confident in our strategy of focusing investment on our internal R&D capabilities while exploring potential external collaborations as well as in our ability to deliver breakthroughs to patients and value to shareholders. With that, let me turn the call over to George.

最後，我們對將投資重點放在內部研發能力、同時探索潛在的外部合作的戰略以及為患者帶來突破和為股東創造價值的能力充滿信心。現在，讓我把電話轉給喬治。

Thank you, Len. I would like to start with our recent update on the aflibercept 8-milligram data in DME that Len referred to. At the Annual American Society of Retina Specialists Meeting, we presented the 2-year results from our PHOTON study. These data demonstrated that the vast majority aflibercept 8-milligram patients randomized to the 12-week and 16-week dosing intervals continued to sustain vision and atomic improvements through 96 weeks. 89% Of all aflibercept 8-milligram patients were able to maintain at least every 12-week dosing intervals for the entire 2-year period, while 84% of patients assigned to every 16-week dosing at baseline, we're able to maintain that interval or extend beyond it.

謝謝你，萊恩。我想從 Len 提到的 DME 中阿柏西普 8 毫克數據的最新更新開始。在美國視網膜專家協會年度會議上，我們展示了 PHOTON 研究的 2 年結果。這些數據表明，絕大多數阿柏西普 8 毫克患者被隨機分配到 12 周和 16 週給藥間隔，在 96 週內繼續維持視力和原子質量改善。在所有阿柏西普 8 毫克患者中，89% 能夠在整個 2 年期間維持至少每 12 週一次給藥間隔，而 84% 的患者在基線時分配為每 16 週一次給藥，我們能夠維持該間隔或超出該間隔。

On that point, many patients met the criteria for extension to longer intervals with 44% meeting the criteria for greater than 20-week dosing intervals, including 27% who are eligible for 24-week dosing. The safety profile of aflibercept 8-milligram remained consistent with EYLEA. Sustaining vision and anatomic improvements while maintaining such extended dosing intervals over 2 years is unprecedented in the field.

在這一點上，許多患者符合延長給藥間隔的標準，其中 44% 的患者符合超過 20 週給藥間隔的標準，其中 27% 的患者符合 24 週給藥的條件。 8 毫克阿柏西普的安全性與 EYLEA 保持一致。在維持視力和解剖學改善的同時保持如此長的給藥間隔長達兩年以上，這在該領域是史無前例的。

Our results further strengthen the clinical profile of aflibercept 8-milligram and position this investigational medicine to become the future standard of care for retinal diseases. Later in the third quarter, we and Bayer our plan to share initial results from the second year analysis of the PULSAR study in patients with wet AMD.

我們的結果進一步強化了阿柏西普 8 毫克的臨床特徵，並使該研究藥物成為未來視網膜疾病的治療標準。在第三季度晚些時候，我們和拜耳計劃分享濕性 AMD 患者 PULSAR 研究第二年分析的初步結果。

Moving to our immunology and inflammation pipeline on Dupixent. We look forward to the FDA decision for our sBLA in chronic spontaneous urticaria by October 22, 2023. In terms of DUPIXENT in patients with COPD, we and Sanofi are pleased to announce that DUPIXENT was granted breakthrough designation for uncontrolled COPD with a near synetelotype based on the positive results of the Phase III BOREAS study.

轉向我們在 Dupixent 上的免疫學和炎症管道。我們期待FDA 於2023 年10 月22 日就我們治療慢性自發性蕁麻疹的sBLA 作出決定。就DUPIXENT 治療慢性阻塞性肺病患者而言，我們和賽諾菲很高興地宣布，DUPIXENT 被授予突破性認定，用於治療不受控制的慢性阻塞性肺病，具有近同絲基因型關於 BOREAS III 期研究的積極結果。

Based on ongoing discussions with the FDA, we expect that in addition to the BOREAS results, we will need to provide data from the Replicate Phase III NOTUS study to support a BLA and such data requirements remain under discussion with the FDA.

根據與 FDA 正在進行的討論，我們預計除了 BOREAS 結果之外，我們還需要提供重複 III 期 NOTUS 研究的數據來支持 BLA，並且此類數據要求仍在與 FDA 討論中。

We continue to expect final results for the NOTUS study by mid-2024. Moving to itepekimab, our anti-IL-33 antibody, which is being evaluated for COPD and former smokers. In May, Sanofi announced that the Phase III AERIFY-1 and 2 studies had passed an interim futility analysis. These studies remain on track for readout and regulatory submissions in 2025. And both itepekimab and DUPIXENT could transform the treatment paradigm for COPD by levering their distinct mechanism of action in reducing different types of inflammation that contribute to COPD.

我們預計 NOTUS 研究的最終結果將在 2024 年中期公佈。轉向 itepekimab，我們的抗 IL-33 抗體，正在針對慢性阻塞性肺病和戒菸者進行評估。 5月，賽諾菲宣布III期AERIFY-1和2研究已通過中期無效分析。這些研究仍有望在 2025 年公佈並提交監管申請。itepekimab 和 DUPIXENT 都可以通過利用其獨特的作用機制來減少導致 COPD 的不同類型的炎症，從而改變 COPD 的治療模式。

Moving to oncology and combinations with Libtayo. In June, in an oral presentation at the ASCO conference, we presented data for the combination of fianlimab, our LAG3 antibody plus Libtayo which showed consistent response rates ranging from 56% to 63% across three independent cohorts of advanced melanoma patients including a new cohort of patients who had received prior anti-PD-1 therapy in the adjuvant melanoma setting.

轉向腫瘤學以及與 Libtayo 的聯合治療。 6 月，在ASCO 會議上的口頭報告中，我們展示了fianlimab、我們的LAG3 抗體與Libtayo 組合的數據，該組合在三個獨立的晚期黑色素瘤患者隊列（包括一個新隊列）中顯示出一致的緩解率，範圍為56% 至63%先前在黑色素瘤輔助治療中接受過抗 PD-1 治療的患者。

These response rates represent about double the rate historically seen with anti-PD-1 monotherapy in similar settings, and clinically meaningful responses were observed in post-hoc analysis of various populations of interest including patients with poor prognosis factors and varying tumor PD-L1 expression levels.

這些緩解率大約是歷史上類似情況下抗PD-1 單藥治療的兩倍，並且在對各種感興趣人群（包括具有不良預後因素和不同腫瘤PD-L1 表達的患者）的事後分析中觀察到具有臨床意義的緩解水平。

The safety profile of fianlimab and the Libtayo combination in these cohorts appears to be generally consistent with the safety profile of the Libtayo monotherapy and other anti-PD-1 or PD-L1 agents, except for the higher rates of adrenaline sufficiency, which were grade 2 or lower in the majority of cases.

在這些隊列中，fianlimab 和 Libtayo 組合的安全性似乎與 Libtayo 單藥療法和其他抗 PD-1 或​​ PD-L1 藥物的安全性總體一致，但腎上腺素充足率較高，為 1 級。大多數情況下為2 或更低。

With all cases successfully managed with steroid replacement. Our Fianilimab plus Libtayo Phase III studies in metastatic and adjuvant melanoma are enrolling patients as are the Phase II portions of the Phase II/III studies in advanced non-small cell lung cancer.

所有病例均通過類固醇替代成功治療。我們針對轉移性和輔助性黑色素瘤的 Fianilimab 加 Libtayo III 期研究正在招募患者，晚期非小細胞肺癌 II/III 期研究的 II 期部分也是如此。

Next, on to bispecifics for solid tumors, which are being investigated in combination with Libtayo and other modalities. Later this year, we are planning to share initial clinical data for the combination of ubamatamab, our MUC16xCD28 bispecific plus Libtayo in advanced ovarian cancer.

接下來，關於實體瘤的雙特異性藥物，目前正在與 Libtayo 和其他方式相結合進行研究。今年晚些時候，我們計劃分享 ubamatamab、我們的 MUC16xCD28 雙特異性藥物與 Libtayo 組合治療晚期卵巢癌的初步臨床數據。

Last year, we showed encouraging ubamatamab monotherapy data in advanced ovarian cancer, and we believe that combining it with Libtayo may lead to enhanced anti-tumor activity.

去年，我們展示了 ubamatamab 單藥治療晚期卵巢癌的令人鼓舞的數據，我們相信將其與 Libtayo 結合可能會增強抗腫瘤活性。

Moving to costimulatory bispecifics. We are currently exploring multiple different CD28 costimulatory bispecific antibodies in early clinical trials in a variety of tumor settings in combination with Libtayo, or with corresponding CD3 bispecifics.

轉向共刺激雙特異性。我們目前正在各種腫瘤環境的早期臨床試驗中探索多種不同的 CD28 共刺激雙特異性抗體與 Libtayo 或相應的 CD3 雙特異性抗體的組合。

In our Phase I study of ReGen 5678, our PSMA by CD28 costimulatory bispecific in advanced prostate cancer in combination with Libtayo which has demonstrated promising antitumor activity. The safety profile of this combination continues to pose a challenge, highlighted by a recently observed second grade 5 adverse event or death. Although serious immune-mediated adverse events continue to be highly correlated to patients who experience profound responses, we have decided to discontinue enrollment of new patients with the full dose Libtayo combination.

在我們對 ReGen 5678 的 I 期研究中，我們的 PSMA by CD28 共刺激雙特異性藥物與 Libtayo 聯合治療晚期前列腺癌，已證明具有良好的抗腫瘤活性。這種組合的安全性繼續構成挑戰，最近觀察到的二級 5 級不良事件或死亡凸顯了這一挑戰。儘管嚴重的免疫介導的不良事件仍然與經歷深刻反應的患者高度相關，但我們決定停止接受全劑量 Libtayo 組合的新患者入組。

And explore PSMA by CD28 combination with lower doses of Libtayo. We also will continue to explore PSMA by CD28 as a monotherapy where we are seeing antitumor activity in some patients and we will explore PSMA by CD28 in combination with other immunotherapy modalities.

並通過CD28與較低劑量的Libtayo組合探索PSMA。我們還將繼續探索 CD28 的 PSMA 作為單一療法，我們在一些患者中看到了抗腫瘤活性，我們將探索 CD28 的 PSMA 與其他免疫治療方式的結合。

We believe our prostate cancer data support the exciting potential of cost inventory bispecifics, but with the challenge of focusing the response sold to the tumor. Our preclinical studies and mechanistic insights suggest a degree of immune-related adverse events seen when combining costims with PD-1 blockade may depend on the particular cost on target and tumor type.

我們相信，我們的前列腺癌數據支持成本庫存雙特異性藥物令人興奮的潛力，但面臨著將反應集中於腫瘤的挑戰。我們的臨床前研究和機制見解表明，將 costim 與 PD-1 阻斷劑聯合使用時出現的免疫相關不良事件的程度可能取決於靶點和腫瘤類型的特定成本。

Moreover, combining costims with CD3 bispecifics may not result in these types of severe immune-mediated adverse events. Along these lines, our other cost inventory bispecific programs continue, including our MUC16xCD28 costim with Libtayo and our MUC16xCD28 costim with ubumatamab, both in ovarian cancer. As well as our EGFR by CD28 costim with Libtayo in colorectal and other cancers.

此外，將 costim 與 CD3 雙特異性藥物組合可能不會導致這些類型的嚴重免疫介導的不良事件。沿著這些思路，我們的其他成本庫存雙特異性項目仍在繼續，包括我們的 MUC16xCD28 costim 與 Libtayo 以及我們的 MUC16xCD28 costim 與 ubumatamab ，均用於卵巢癌。以及我們的 EGFR by CD28 costim 與 Libtayo 治療結直腸癌和其他癌症。

In these early dose escalation studies, we have observed limited immune-mediated toxicities to date. We're also excited about combining our costimulatory bispecifics with our CD3 bispecifics in our hem/onc programs, which continue to progress. We have initiated dosing of our CD22xCD20 costimulatory bispecific with our odronextamab CD20xCD3 bispecific in relapsed/refractory diffuse large B-cell lymphoma, which we hope can improve on the impressive efficacy demonstrated by odronextamab alone in that setting.

在這些早期劑量遞增研究中，迄今為止我們觀察到了有限的免疫介導的毒性。我們也很高興能夠在 hem/onc 項目中將我們的共刺激雙特異性藥物與 CD3 雙特異性藥物相結合，該項目正在不斷取得進展。我們已經開始在復發/難治性瀰漫性大B 細胞淋巴瘤中使用我們的CD22xCD20 共刺激雙特異性藥物與odronextamab CD20xCD3 雙特異性藥物，我們希望能夠在單獨使用odronextamab 時所表現出的令人印象深刻的療效上有所提高。

In terms of odronextamab monotherapy, U.S. and EU regulatory submissions for both relapsed or refractory follicular lymphoma and diffuse large B-cell lymphoma remain on track. Regarding linvoseltamab or BCMA by CD3 bispecific, we recently presented updated data at the ASCO annual meeting, demonstrating early, deep and durable responses in patients with heavily pretreated a myeloma with 71% objective response rate and 59% of patients achieving a very good partial response or better at the recommended 200-milligram dose with a median follow-up of only 6 months with the data potentially improving as they mature.

就 odronextamab 單藥治療而言，美國和歐盟針對複發或難治性濾泡性淋巴瘤和瀰漫性大 B 細胞淋巴瘤的監管提交仍在進行中。關於CD3雙特異性的linvoseltamab或BCMA，我們最近在ASCO年會上提供了最新數據，證明了對經過大量預處理的骨髓瘤患者的早期、深度和持久的緩解，客觀緩解率為71%，59 %的患者達到了非常好的部分緩解或在推薦的 200 毫克劑量下效果更好，中位隨訪時間僅為 6 個月，隨著數據的成熟，數據可能會有所改善。

We believe these data support linvoseltimab's best-in-class potential with differentiated efficacy, safety, hospital requirements and favorable dosing schedule. In the fourth quarter of this year, we are planning to present additional data with longer follow-up and to submit regulatory applications for linvoseltamab.

我們相信這些數據支持林沃塞替單抗具有差異化療效、安全性、醫院要求和有利的給藥方案的同類最佳潛力。今年第四季度，我們計劃提供更多長期隨訪數據，並提交 linvoseltamab 的監管申請。

We also plan to start combination sites with a myeloma-specific costim next year.

我們還計劃明年啟動針對骨髓瘤的 Costim 的聯合治療。

Next, to genetic medicines. In the second quarter, we and Alnylam jointly announced the first human data suggesting that an siRNA can be used to silence pathological genes in the brain. Which may open up an entirely new approach for fighting back against neurodegenerative and other central nervous system diseases.

接下來是基因藥物。第二季度，我們和 Alnylam 聯合公佈了第一個人體數據，表明 siRNA 可用於沉默大腦中的病理基因。這可能會開闢一種對抗神經退行性疾病和其他中樞神經系統疾病的全新方法。

We plan to initiate additional clinical programs for CNS diseases next year. As announced by our collaborators at Intellia, we plan to initiate the first in vivo CRISPR-based Phase III clinical program by year-end. Subject to regulatory feedback in patients with transthyretin amyloidosis cardiomyopathy.

我們計劃明年啟動更多針對中樞神經系統疾病的臨床項目。正如我們在 Intellia 的合作者所宣布的，我們計劃在年底前啟動第一個基於 CRISPR 的體內 III 期臨床項目。需接受運甲狀腺素蛋白澱粉樣變性心肌病患者的監管反饋。

And in terms of our targeted gene delivery pipeline, we hope to initiate our first clinical program in 2024 for hemophilia B.

就我們的靶向基因遞送管道而言，我們希望在 2024 年啟動第一個針對 B 型血友病的臨床項目。

In conclusion, Regeneron's R&D engine continues to grow and deliver differentiated late and early-stage opportunities, and we are looking forward to several important clinical milestones in the second half of this year.

總之，再生元的研發引擎繼續增長，並提供差異化​​的後期和早期機會，我們期待今年下半年實現幾個重要的臨床里程碑。

With that, I will turn the call over to Marion.

這樣，我會將電話轉給馬里昂。

Thank you, George. In the second quarter, Regeneron delivered impressive results across our commercial portfolio. Notably, Regeneron medicines currently lead multiple disease categories and our future is promising with short- and longer-term scientific innovations on the horizon.

謝謝你，喬治。第二季度，再生元在我們的商業產品組合中取得了令人印象深刻的業績。值得注意的是，再生元藥物目前在多種疾病類別中處於領先地位，隨著短期和長期科學創新的出現，我們的未來充滿希望。

As Len mentioned, we eagerly await the anticipated approval of aflibercept 8-milligram for retinal diseases. Beyond that, a robust late-stage pipeline supports additional commercial opportunities that we anticipate will continue to drive growth.

正如 Len 提到的，我們熱切地等待 8 毫克阿柏西普治療視網膜疾病的預期批准。除此之外，強大的後期管道支持額外的商業機會，我們預計這些機會將繼續推動增長。

Starting with EYLEA, the anti-VEGF category leader in retinal diseases. U.S. IDEA net sales were $1.5 billion, down 7% year-over-year and up 5% quarter-over-quarter. EYLEA total category share's remained stable at 46% over the last two quarters and at approximately 70% for branded share. At the end of the second quarter, there was minimal sequential change in wholesaler inventory levels compared to the levels at the end of the first quarter.

從 EYLEA 開始，EYLEA 是視網膜疾病領域抗 VEGF 類別的領導者。美國IDEA淨銷售額為15億美元，同比下降7%，環比增長5%。 EYLEA 過去兩個季度的總類別份額穩定在 46%，品牌份額約為 70%。與第一季度末的水平相比，第二季度末批發商庫存水平的環比變化很小。

Our strategic focus is to maintain and grow Regeneron's anti-VEGF leadership, and we're well positioned to deliver on this goal in an increasingly competitive category. Last week at ASRS, we presented our 2-year data in diabetic macular edema, which further confirmed the unprecedented durability of aflibercept 8 milligram, with 44% of patients has signed intervals of at least 20 weeks at the end of their second year.

我們的戰略重點是維持和發展 Regeneron 在抗 VEGF 領域的領先地位，並且我們有能力在競爭日益激烈的領域實現這一目標。上週在 ASRS 上，我們展示了糖尿病黃斑水腫的 2 年數據，進一步證實了阿柏西普 8 毫克前所未有的持久性，44% 的患者在第二年末簽署了至少 20 週的間隔期。

Market enthusiasm remains high for this important innovation and our commercial team is ready and excited to launch aflibercept 8-milligram upon approval.

市場對這一重要創新的熱情仍然很高，我們的商業團隊已準備好並興奮地在獲得批准後推出阿柏西普 8 毫克。

Moving now to Libtayo. Global net sales were $210 million, up 49% year-over-year on a constant currency basis. In the U.S., net sales were $130 million, up 43% and driven by steady growth in non-melanoma skin cancer and strong growth in lung cancer. In lung cancer Libtayo use in new patient shares accelerating both monotherapy and in combination with chemotherapy. With an expanding base of prescribers in the community and academic settings. Outside the U.S., Libtayo net sales were $80 million, a 58% increase on a constant currency basis. Growth was driven by demand in the non-melanoma skin cancer indications and initial launches in lung cancer.

現在搬到利塔約。全球淨銷售額為 2.1 億美元，按固定匯率計算同比增長 49%。在美國，受非黑色素瘤皮膚癌穩步增長和肺癌強勁增長的推動，淨銷售額為 1.3 億美元，增長 43%。在肺癌中，Libtayo 在新患者中的使用可以加速單一療法和與化療的聯合治療。隨著社區和學術環境中處方者基礎的不斷擴大。在美國以外，Libtayo 的淨銷售額為 8000 萬美元，按固定匯率計算增長 58%。增長是由非黑色素瘤皮膚癌適應症的需求和肺癌的初步推出推動的。

We expect to drive accelerated performance as we build Regeneron's presence in key international markets and secure access and reimbursement for lung cancer indications. And lastly, to DUPIXENT, which continues to revolutionize the lives of patients with type 2 diseases. Global net sales were approximately $2.8 billion, up 34% year-over-year on a constant currency basis and up 12% compared to the first quarter of 2023.

隨著我們在主要國際市場建立再生元的影響力並確保肺癌適應症的獲取和報銷，我們預計將推動業績加速增長。最後，DUPIXENT 繼續徹底改變 2 型疾病患者的生活。全球淨銷售額約為 28 億美元，按固定匯率計算同比增長 34%，與 2023 年第一季度相比增長 12%。

In the U.S., net sales grew 33% year-over-year to $2.1 billion, driven by growth across all indications and age groups. Once again, DUPIXENT is the #1 prescribed biologic medicine for new-to-brand patients across all approved indications and is the category leader in total prescriptions in 4 out of 5 indications. We see impressive uptake across our recent U.S. launches with significant opportunity for future growth.

在美國，受所有適應症和年齡組增長的推動，淨銷售額同比增長 33%，達到 21 億美元。 DUPIXENT 再次成為新品牌患者在所有批准適應症中排名第一的處方生物藥物，並且在 5 個適應症中的 4 個適應症中的總處方類別中處於領先地位。我們看到最近在美國推出的產品獲得了令人印象深刻的採用，並為未來的增長提供了巨大的機會。

In eosinophilic esophagitis, well over 15,000 patients have been initiated since launch, and we are actively investing in disease awareness initiatives to empower patients to seek diagnosis and treatment for this debilitating disease. Our pruigo nodularis launch is off to a fast start with physicians rapidly recognizing DUPIXENT as the go-to treatment for this often underdiagnosed dermologic conditions.

在嗜酸性粒細胞性食管炎方面，自推出以來已吸引了超過 15,000 名患者參與，我們正在積極投資於疾病意識活動，以使患者能夠就這種使人衰弱的疾病尋求診斷和治療。我們的結節性癢疹的推出很快就開始了，醫生很快就認識到 DUPIXENT 是治療這種經常被診斷不足的皮膚病的首選治療方法。

Additionally, we look forward to our October 22 PDUFA date. In chronic spontaneous urticaria, where we estimate DUPIXENT could benefit up to 300,000 U.S. patients. We also continue to generate impressive growth across atopic dermatitis, asthma and nasal polyps, DUPIXENT's three largest indications.

此外，我們期待 10 月 22 日的 PDUFA 日期。在慢性自發性蕁麻疹方面，我們估計 DUPIXENT 可以使多達 300,000 名美國患者受益。我們還在特應性皮炎、哮喘和鼻息肉（DUPIXENT 的三大適應症）領域繼續取得令人印象深刻的增長。

There is robust demand among all indicated age groups with a significant opportunity for future growth beyond the hundreds of thousands of patients around the world whose lives have already been transformed by DUPIXENT.

所有指定年齡組都有強勁的需求，除了世界各地已經因 DUPIXENT 改變生活的數十萬患者之外，未來還有巨大的增長機會。

In summary, we delivered a strong commercial performance in the second quarter with Regeneron's Medicines position for sustained growth. We continue to demonstrate industry-leading execution across our current portfolio, and we are prepared to maximize opportunities from our robust pipeline with the goal of extending Regeneron's scientific innovations to even more patients. Now I will turn the call over to Bob.

總而言之，我們在第二季度取得了強勁的商業業績，再生元的藥品地位持續增長。我們將繼續在當前的產品組合中展示行業領先的執行力，並準備充分利用我們強大的產品線中的機會，目標是將再生元的科學創新擴展到更多患者。現在我將把電話轉給鮑勃。

Thank you, Marion. My comments today on Regeneron's financial results and outlook will be on a non-GAAP basis unless otherwise noted. Regeneron's second quarter results demonstrate continued growth and strong financial performance across the organization.

謝謝你，馬里昂。除非另有說明，我今天對再生元的財務業績和前景的評論將基於非公認會計原則。再生元第二季度業績表明整個組織的持續增長和強勁的財務業績。

Second quarter 2023 total revenues increased 11% and year-over-year to $3.2 billion, driven by strong DUPIXENT sales growth, coupled with improving profitability within our Sanofi collaboration and continued momentum from Libtayo.

得益於 DUPIXENT 銷售強勁增長、我們與賽諾菲合作盈利能力的提高以及 Libtayo 的持續增長勢頭，2023 年第二季度總收入同比增長 11%，達到 32 億美元。

Second quarter diluted net income per share was $10.24 on net income of $1.2 billion. Moving to collaboration revenue and starting with Bayer. Second quarter 2023 ex U.S. EYLEA net product sales were $886 million, up 4% on a constant currency basis versus second quarter 2022. Total Bayer collaboration revenue was $377 million, of which $350 million related to our share of EYLEA net profits outside the U.S.

第二季度稀釋後每股淨利潤為 10.24 美元，淨利潤為 12 億美元。轉向合作收入並從拜耳開始。 2023 年第二季度（美國除外）EYLEA 淨產品銷售額為8.86 億美元，按固定匯率計算比2022 年第二季度增長4%。拜耳合作總收入為3.77 億美元，其中3.5 億美元與我們在美國以外的EYLEA 淨利潤中所佔的份額有關。

Total Sanofi collaboration revenue was $944 million in the second quarter and grew 39% versus the prior year. Our share of profits from the commercialization of DUPIXENT and KEVZAR was $751 million, an increase of 51% from the second quarter of 2022, reflecting higher volumes and an improving margin profile for DUPIXENT.

第二季度賽諾菲合作總收入為 9.44 億美元，較上年增長 39%。我們從 DUPIXENT 和 KEVZAR 商業化中獲得的利潤份額為 7.51 億美元，較 2022 年第二季度增長 51%，反映出 DUPIXENT 銷量的增加和利潤率的改善。

We expect further margin expansion from the collaboration driven by continued DUPIXENT global sales growth, coupled with higher gross margins due to significant drug substance yield improvements resulting from dupilumab manufacturing process enhancements. These factors are also contributing to a gradual increase in the rate in which we are repaying the antibody development balance to Sanofi.

我們預計，在 DUPIXENT 全球銷售持續增長的推動下，此次合作的利潤率將進一步擴大，同時由於 dupilumab 製造工藝的改進，原料藥產量顯著提高，毛利率也將提高。這些因素也促使我們向賽諾菲償還抗體開發餘額的比率逐漸提高。

Once this balance is fully repaid in the next few years, we expect a meaningful step-up in our share of Sanofi collaboration profits. Recall that a portion of our Sanofi collaboration revenue is related to the manufacturing of commercial supplies for which we are reimbursed by Sanofi as we continue to phase in the higher yield manufacturing process for DUPIXENT. We expect these second half reimbursements to be approximately 25% lower than the first half of 2023, with the fourth quarter expected to be the lowest of the year.

一旦這筆餘額在未來幾年內完全償還，我們預計我們在賽諾菲合作利潤中的份額將出現有意義的提升。回想一下，我們的賽諾菲合作收入的一部分與商業用品的製造有關，隨著我們繼續分階段採用更高產量的 DUPIXENT 製造工藝，我們將得到賽諾菲的補償。我們預計下半年的報銷金額將比 2023 年上半年減少約 25%，其中第四季度預計將是全年最低的。

Other revenues were $69 million in the second quarter, up 17% versus the prior year. We continue to expect other revenue to be higher in the second half of 2023 as compared to the first half. Recall that other revenue primarily includes reimbursements for the manufacturing of certain Regeneron discovered products commercialized by other companies, including ex-U.S. PRALUENT ARCALYST and ZALTRAP as well as royalties for Alaris and in our share of global profits for Arcilist.

第二季度其他收入為 6900 萬美元，比去年同期增長 17%。我們繼續預計 2023 年下半年的其他收入將高於上半年。回想一下，其他收入主要包括再生元發現的由其他公司（包括美國以外的公司）商業化的某些產品的製造費用。 PRALUENT ARCALYST 和 ZALTRAP 以及 Alaris 的特許權使用費以及我們在 Arcilist 的全球利潤中的份額。

Moving now to our operating expenses. Second quarter 2023. R&D expense was $974 million, representing continued investment in our robust pipeline. Year-over-year R&D growth was primarily driven by higher head count and related costs in funding of the company's pipeline, which encompasses approximately 20 late-stage or potentially registrational studies, including our ongoing aflipercept-8 mg studies. Phase III studies in earlier lines of therapy for our hem/onc product candidates and our advancing fianlimab development program.

現在轉向我們的運營費用。 2023 年第二季度。研發費用為 9.74 億美元，表明我們對強大的產品線進行了持續投資。研發同比增長主要是由於人員數量增加以及公司管道融資的相關成本推動的，其中包括約 20 項後期或潛在註冊研究，包括我們正在進行的 aflipercept-8 mg 研究。我們的 hem/onc 產品候選者的早期治療系列和我們先進的 fianlimab 開發計劃的 III 期研究。

The increase in R&D expense was also driven in part by the impact of the 2022 amendments to the Sanofi collaboration agreement and increased manufacturing activity associated with the company's earlier stage product candidates. SG&A was $562 million in the second quarter, reflecting the ongoing build-out of our ex U.S. operations following the acquisition of global rights to Libtayo last year, higher head count and related costs and higher contributions to an independent not-for-profit patient assistance organization.

研發費用的增加部分是由於賽諾菲合作協議 2022 年修訂以及與該公司早期候選產品相關的製造活動增加的影響。第二季度的銷售及管理費用為 5.62 億美元，反映了去年收購 Libtayo 的全球權利後我們在美國以外的業務的持續擴張、員工人數和相關成本的增加以及對獨立非營利患者援助的貢獻增加組織。

Second quarter 2023 COCM was $213 million, up 44% versus the prior year. driven by manufacturing costs associated with higher DUPIXENT volumes. As we progress the phasing of the improved manufacturing process for DUPIXENT, we expect COCM in the second half of this year to decline versus the first half as our unchanged 2023 COCM guidance reflects with the fourth quarter expected to be the lowest of the year.

2023 年第二季度 COCM 為 2.13 億美元，比上年增長 44%。受到與 DUPIXENT 產量增加相關的製造成本的推動。隨著我們逐步推進 DUPIXENT 改進的製造工藝，我們預計今年下半年的 COCM 將較上半年下降，因為我們不變的 2023 年 COCM 指導反映了第四季度預計將是今年最低的。

Now to cash flow and the balance sheet. In the first half of 2023, Regeneron generated approximately $2.1 billion in free cash flow we ended the second quarter with cash and marketable securities less debt of approximately $12.6 billion. We continue to opportunistically deploy cash towards share repurchases throughout the second quarter buying back $723 million of our shares. At current levels, we remain buyers of our shares.

現在來看看現金流量和資產負債表。 2023 年上半年，再生元產生了約 21 億美元的自由現金流，截至第二季度末，現金和有價證券減去約 126 億美元的債務。我們在第二季度繼續機會性地部署現金進行股票回購，回購了 7.23 億美元的股票。在目前的水平上，我們仍然是我們股票的買家。

And as of June 30, approximately $2.3 billion remained available for repurchases under our existing authorization.

截至 6 月 30 日，根據我們現有的授權，仍有約 23 億美元可用於回購。

Finally, we've made some minor changes to our full year 2023 guidance ranges based on our first half results and our latest outlook for the remainder of the year, we have tightened guidance ranges for 2023 SG&A and R&D spend and provided updated guidance ranges for our effective tax rate.

最後，我們根據上半年業績和對今年剩餘時間的最新展望，對 2023 年全年指導範圍進行了一些細微調整，我們收緊了 2023 年 SG&A 和研發支出的指導範圍，並提供了更新的指導範圍我們的有效稅率。

A complete summary of our latest full year guidance is available in our press release issued earlier this morning.

今天上午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。

In conclusion, Regeneron delivered positive financial results in the second quarter of 2023 and we remain excited for the potential upcoming launch of aflibercept 8 mg in the third quarter. With that, I will now pass the call back to Ryan.

總之，再生元在 2023 年第二季度取得了積極的財務業績，我們對第三季度可能推出的阿柏西普 8 毫克仍然感到興奮。現在，我將把電話轉回給瑞安。

Thank you, Bob. 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 only be able to answer one question from each caller before moving to the next. Shannon, can we go to the first question, please?

謝謝你，鮑勃。我們準備好的發言到此結束。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，我們只能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) Our first question comes from the line of Evan Seigerman with BMO.

（操作員說明）我們的第一個問題來自 BMO 的 Evan Seigerman。

On all the updates today. So on the 8-milligram CRL, do you have any idea if it's a Class I or Class II resubmission? And you say that FDA is going to take action in the third quarter or could take action. What does that mean? Are they going to provide an approval decision? Or is that just going to be acceptance of a refiling.

關於今天的所有更新。那麼對於 8 毫克 CRL，您知道它是 I 類還是 II 類重新提交嗎？你說FDA將在第三季度採取行動或者可能採取行動。這意味著什麼？他們會提供批准決定嗎？或者這只是接受重新歸檔。

Evan, it's Len. Thanks for your question. So just to clarify, the FDA has not classified the resubmission as Class I or Class II because they have said that the time line for pozelimab will be governing what happens with our 8 milligrams. So let me remind you what happened. There was a pre-approval inspection for both products. the pozelimab is for our ultra rare disease chapel disease, and it has a PDUFA date of the 20th.

埃文，是萊恩。謝謝你的提問。因此，澄清一下，FDA 並未將重新提交歸類為 I 類或 II 類，因為他們表示 pozelimab 的時間表將決定我們 8 毫克的情況。所以讓我提醒你發生了什麼事。這兩種產品都經過了批准前檢查。 pozelimab 用於治療我們的超罕見疾病教堂疾病，其 PDUFA 日期為 20 日。

What the FDA has said is that they will review the remediation efforts in the context of the pozelimab BLA. And therefore, whatever happens there will govern the time line and results. And when we say we expect them to take action, we mean that we expect them to make an approval or not decision.

FDA 表示，他們將在 pozelimab BLA 的背景下審查補救措施。因此，無論發生什麼，都將決定時間線和結果。當我們說我們希望他們採取行動時，我們的意思是我們希望他們做出批准或不批准的決定。

If they find the manufacturing remediation acceptable for the pozelimab, then we think they'll be in a position to promptly make a decision on approval for the 8 milligrams. Does that answer your question?

如果他們發現 pozelimab 的生產補救措施可以接受，那麼我們認為他們將能夠迅速做出批准 8 毫克的決定。這是否回答你的問題？

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

我們的下一個問題來自 Tyler Van Buren 和 TD Cowen 的對話。

So the time line to the FDA potentially taking action by the end of this quarter on (inaudible) is very encouraging. Investors are clearly surprised by the short line. So kudos to you all for executing but as we think about the data submission in a couple of weeks, what additional details can you provide regarding the manufacturing data and other information that are required from Catalent and how feasible it is to review this in a few days prior to the pozelimab decision date on August 20.

因此，FDA 可能在本季度末採取行動（聽不清）的時間表非常令人鼓舞。投資者顯然對短線感到驚訝。感謝大家的執行，但當我們考慮在幾週內提交數據時，您可以提供有關康泰倫特所需的製造數據和其他信息的其他詳細信息，以及在幾週內審核此信息的可行性。 8月20 日pozelimab 決定日期前幾天。

Right. Great question. So we've been in very close contact with Catalent and the FDA with multiple meetings, oral, written and so forth. And we have a clear understanding of what's required from an information point of view and from a data point of view.

正確的。很好的問題。因此，我們通過多次會議、口頭、書面等方式與康泰倫特和 FDA 保持著非常密切的聯繫。我們從信息的角度和數據的角度清楚地了解需要什麼。

The submissions have been on a rolling basis that as Catalent has completed work, they've submitted data and information already to the FDA. There is very little that will be left for the last submission at the middle of August.

這些提交是在滾動的基礎上進行的，隨著 Catalent 完成工作，他們已經向 FDA 提交了數據和信息。八月中旬最後一次提交的作品所剩無幾。

And that's why the FDA has told us and they know what's coming, that they will strive to expeditiously review that. If they can't get that done by the few days before the pozelimab PDUFA date, they have told us that they will prioritize our review and do that as soon as possible.

這就是為什麼 FDA 告訴我們，他們知道將會發生什麼，他們將努力迅速審查。如果他們無法在 pozelimab PDUFA 日期前幾天完成這項工作，他們會告訴我們，他們將優先考慮我們的審查並儘快完成。

That's why we have confidence about this getting done in this quarter.

這就是為什麼我們對本季度完成這項工作充滿信心。

So to summarize, the data has been coming in on a rolling basis. We have everything we need on the last piece of information that we'll be rolling in and submitted by the middle of the month. the FDA will strive expeditiously to review that return in time for the August 20 PDUFA date.

總而言之，數據是滾動輸入的。我們已經掌握了最後一條信息所需的一切，我們將在本月中旬之前滾動並提交這些信息。 FDA 將努力在 8 月 20 日 PDUFA 日期之前及時審查該申報表。

But if not, there'll be a clock extension for up to 3 months, but they have told us that they will prioritize our review. And that's why we believe it will get done, if not in time for the pozelimab PDUFA date, in the near future thereafter.

但如果沒有的話，時間會延長最多 3 個月，但他們告訴我們，他們會優先考慮我們的審核。這就是為什麼我們相信即使不能及時趕上 pozelimab PDUFA 日期，也會在不久的將來完成。

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

我們的下一個問題來自富國銀行的莫希特·班薩爾 (Mohit Bansal)。

And really thank you very much for providing all the clarity on the filing situation right now. Maybe taking -- so just trying to understand this a little bit more. So is it fair to say you have already submitted everything for pozelimab. And the remaining part related to high-dose EYLEA only. Is that fair?

真的非常感謝您現在提供有關申請情況的所有說明。也許需要——所以只是想更多地理解這一點。那麼，可以公平地說您已經提交了 pozelimab 的所有內容嗎？其餘部分僅與高劑量EYLEA有關。這公平嗎？

Actually, the way you should think about it, we've submitted everything we need for pozelimab except for the final remediation of the preapproval inspection, which applies both to pozelimab and to the 8-milligram EYLEA. So it's a single preapproval inspection, same data and information required for both. Once that is in, then we will have completed everything necessary for pozelimab and for the EYLEA 8 milligrams. They are linked together. The FDA has clearly stated to us that the review of this remediation in the context of the pozelimab BLA will govern what happens to the 8-milligram remediation.

事實上，你應該這樣想，我們已經提交了 pozelimab 所需的一切，除了批准前檢查的最終補救措施，這適用於 pozelimab 和 8 毫克 EYLEA。因此，這是一次預批准檢查，兩者所需的數據和信息相同。一旦完成，我們就完成了 pozelimab 和 EYLEA 8 毫克所需的一切。它們是聯繫在一起的。 FDA 已向我們明確表示，在 pozelimab BLA 背景下對這種補救措施的審查將決定 8 毫克補救措施的情況。

And I think there's nothing specific to either pozelimab or aflibercept about the data. This has to do, as Len said, with general manufacturing processes and operations at the Catalent manufacturing facility, particularly with this one manufacturing line.

我認為這些數據沒有任何具體針對 pozelimab 或 aflibercept 的信息。正如 Len 所說，這與康泰倫特製造工廠的一般製造工藝和操作有關，特別是與這條生產線有關。

Yes. That's a very good point, George. So that's why the single preapproval inspection applies to both products. It wasn't the product specifically, it was the processes and validation on the line that fills the two products. So one remediation satisfies both, all the data and information that are being submitted on a rolling basis. The last piece comes in, in the middle of August, the FDA is aware of this.

是的。這是一個非常好的觀點，喬治。這就是為什麼單一預批准檢查適用於兩種產品的原因。具體來說，這不是產品，而是填充這兩種產品的生產線的流程和驗證。因此，一項補救措施可以同時滿足滾動提交的所有數據和信息。最後一篇文章是在八月中旬發布的，FDA 已經意識到了這一點。

They've told us in writing that they will strive to review that expeditiously. If they get it done before the end of the PDUFA, an original PDUFA clock, that's great. If they don't, they'll consider an amendment that will set the clock back 3 months. But notwithstanding that 3 months, they've told us that they will continue to prioritize our review. So we're very pleased, and we're working very hard. Catalent is working very hard. The FDA is working very hard. Everybody wants this done properly and finished and properly remediated.

他們以書面形式告訴我們，他們將努力迅速進行審查。如果他們在 PDUFA（原始 PDUFA 時鐘）結束之前完成它，那就太好了。如果他們不這樣做，他們將考慮一項修正案，將時間撥回三個月。但儘管已經過去了 3 個月，他們仍然告訴我們，他們將繼續優先考慮我們的審核。所以我們非常高興，而且我們正在努力工作。康泰倫特工作非常努力。 FDA 正在努力工作。每個人都希望這件事得到妥善處理、完成並得到妥善補救。

Our next question comes from the line of Tim Anderson with Wolfe Research.

我們的下一個問題來自沃爾夫研究中心的蒂姆·安德森。

I have a question on the vismo. So (inaudible) Q3 said they're capturing 30% of treatment-naive patients, which seems like a quite high figure, frankly. And then they said afterwards that it's not the extended dosing that's driving this as much as it is the better drawing that they say docs are seeing with their product. I'm wondering how those comments kind of line up to what you're seeing play out in the U.S. market?

我有一個關於 vismo 的問題。所以（聽不清）第三季度表示他們捕獲了 30% 的初治患者，坦率地說，這似乎是一個相當高的數字。然後他們事後說，這並不是延長劑量造成的，而是他們說醫生在他們的產品中看到的更好的繪圖。我想知道這些評論與您所看到的美國市場的情況是否相符？

Sure. So Tim, I will comment on our EYLEA performance. And as I just shared with you, the performance in the quarter was strong. certainly, we see EYLEA steadily as the standard of care in the anti-VEGF category.

當然。蒂姆，我將評論我們 EYLEA 的表現。正如我剛剛與大家分享的那樣，本季度的表現非常強勁。當然，我們認為 EYLEA 穩步成為抗 VEGF 類別的護理標準。

We continue to capture not only naive patients but also another big source of business is switch patients from Avastin.

我們不僅繼續吸引未接受治療的患者，而且另一個重要的業務來源是從阿瓦斯汀轉診的患者。

Obviously, the other branded competitors are smaller in market today. But I would say that beyond your comment, probably best to get more clarification from the individuals who are commercializing fasinumab in the market. But certainly, I do want you to know that we are seeing continued strength in EYLEA performance.

顯然，當今市場上的其他品牌競爭對手規模較小。但我想說的是，除了您的評論之外，最好從在市場上商業化法辛單抗的個人那裡獲得更多澄清。但當然，我確實想讓您知道，我們看到 EYLEA 的表現持續強勁。

And obviously, very much look forward to having the potentially game-changing opportunity bringing aflibercept 8-milligram into the marketplace where the profile of efficacy, safety and durability has so many KOLs and prescribers excited based on what they've seen recently in the clinical data presented at ASRS.

顯然，我們非常期待有可能改變遊戲規則的機會，將8 毫克阿柏西普帶入市場，該市場的功效、安全性和耐用性讓許多KOL 和處方醫生基於他們最近在臨床中看到的情況而感到興奮ASRS 上提供的數據。

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

我們的下一個問題來自克里斯·雷蒙德和派珀·桑德勒的對話。

Just maybe another market VEGF market-related question. So I know these extended dose therapies have benefits in and of themselves on the face of them, but there's been some decent level of market chatter around docs looking to free up injection capacity. Specifically to make room for geographic atrophy patients and specifically with the Apellis drug.

也許只是另一個與 VEGF 市場相關的問題。因此，我知道這些延長劑量的療法本身就具有好處，但圍繞尋求釋放注射能力的醫生，市場上存在一些相當程度的討論。專門為地理萎縮患者騰出空間，特別是使用 Apellis 藥物。

Just maybe curious how widespread was that notion before the [aflibercept] safety issue. And now with the issue, have you noticed a discernible shift among docs who were talking about that. And then maybe a related question. You guys have talked, I think, about an early effort of your own in geographic atrophy. Clearly, the market is sizable. When could we expect to hear more about that effort?

也許只是好奇在[aflibercept]安全問題之前這種想法有多普遍。現在，對於這個問題，您是否注意到正在討論該問題的文檔之間發生了明顯的轉變。然後也許是一個相關的問題。我想，你們已經談到了你們自己在地理萎縮方面的早期努力。顯然，市場規模很大。我們什麼時候可以聽到更多有關這項工作的信息？

So let me share first in terms of the market dynamic. I think the most thing and most important thing about a aflibercept 8-milligram is that it gives prescribers for all of their patients, whether a naive patient, a patient currently on EYLEA or a patient on another anti-VEGF category product the opportunity to decide if that patient is a candidate when we launch and when we have an FDA approval, if the patient is a candidate for aflibercept 8-milligram that does have benefit to the patient and prescriber and potentially to the office capacity and patient flow.

首先讓我分享一下市場動態。我認為阿柏西普8 毫克最重要的一點是，它為所有患者的處方者提供了決定的機會，無論是初次接受治療的患者、目前正在使用EYLEA 的患者還是正在使用另一種抗VEGF 類別產品的患者如果該患者是我們推出時以及獲得FDA 批准時的候選者，如果該患者是8 毫克阿柏西普的候選者，這確實對患者和處方者有利，並可能對辦公室容量和患者流量有利。

I think it's premature to comment on a category that we're not directly involved in. We are, though, very focused on making sure that we are ready for launch and certainly at the proper time, educating all stakeholders on the aflibercept 8-milligram once we have an approval.

我認為現在對我們沒有直接參與的類別發表評論還為時過早。不過，我們非常專注於確保我們準備好上市，當然是在適當的時間，對所有利益相關者進行關於阿柏西普8 毫克的教育一旦我們獲得批准。

And in terms of our own efforts, as I'm sure many of you are aware, we've been very active with what we feel are very innovative approaches in the complement blockade field. And we believe that we may have an approach that may allow potentially treatment in these retinal diseases. While avoiding some of the very concerning adverse events having to do with issues like inclusive vasculitis and so forth, and you'll be hearing much more about those efforts in the short term.

就我們自己的努力而言，我相信你們很多人都知道，我們一直非常積極地採用我們認為在補體封鎖領域非常創新的方法。我們相信，我們可能有一種方法可以潛在地治療這些視網膜疾病。在避免一些與包容性血管炎等問題有關的非常令人擔憂的不良事件的同時，您將在短期內聽到更多有關這些努力的信息。

Our next question comes from the line of Carter Gould with Barclays.

我們的下一個問題來自卡特·古爾德與巴克萊銀行的對話。

Thanks for all the transparency. Maybe switching gears a bit in terms of the update on your costim and the report of the depth and the and the change in the dosing paradigm with 567 in combination with Libtayo. George, maybe you can speak about the implications for other combination efforts of CD28 with Libtayo. Is this going to require a lower dosing with those efforts with the Libtayo portion? And just the broader implications there and just still your level of confidence, you can kind of thread that needle in terms of the dosing levels.

感謝所有的透明度。也許在您的 costim 更新和深度報告以及 567 與 Libtayo 結合的劑量範式的變化方面稍微改變一下。 George，也許你可以談談 CD28 與 Libtayo 的其他組合工作的影響。 Libtayo 部分的這些努力是否需要降低劑量？只要有更廣泛的影響，並且仍然有您的信心水平，您就可以根據劑量水平來確定這一點。

Right. No, great question. Obviously, as you know, in cancer, the biggest hurdle is actually coming up with approaches and new classes of agents that have the ability to really change the efficacy paradigm to really bring new ability to address cancers that have previously been untreatable or refractory to treatment.

正確的。不，很好的問題。顯然，如您所知，在癌症領域，最大的障礙實際上是提出能夠真正改變療效範式的方法和新型藥物，從而真正帶來新的能力來解決以前無法治療或難治的癌症。

So I think that, that excitement continues with the costim platform in terms of all of the science and the preclinical modeling and predictions have really delivered in terms of showing that this new class does seemingly have the ability to really change the efficacy paradigm.

因此，我認為，就所有科學而言，costim 平台的興奮仍在繼續，臨床前建模和預測確實表明了這個新類別似乎確實有能力真正改變功效範式。

But now we have to balance that, as you said, with the safety because with more efficacy, which is often seen in the cancer field comes more safety concerns to what you just said, what we've seen preclinically, and we're now beginning to see it in the clinic, that the amount of associated immune adverse events is related to the particular costim target.

但現在我們必須平衡這一點，正如你所說，與安全性之間的平衡，因為隨著功效的提高，這在癌症領域經常出現，隨之而來的是對你剛才所說的、我們在臨床前所看到的更多安全性擔憂，我們現在臨床上開始發現，相關免疫不良事件的數量與特定的 Costim 目標有關。

So what you see for one costim in doesn't necessarily apply to the other costim in. So we are, as you said, for our PSMA costim, moving out of lower doses of the Libtayo becaus the full dose combination while it seems like it's has the potential to be very efficacious also has, in some cases, these associated only -- remember, only in the patients who are having deep responses, these associated in some cases, that can be very serious, even resulting in death associated in new adverse events.

因此，您所看到的一種 Costim 不一定適用於另一種 Costim。因此，正如您所說，對於我們的 PSMA Costim，我們正在放棄較低劑量的 Libtayo，因為全劑量組合雖然看起來像是有潛力非常有效，在某些情況下，這些僅相關- 請記住，僅在有深度反應的患者中，這些相關在某些情況下可能非常嚴重，甚至導致新的死亡不良事件。

So -- we're moving away from full dose combinations there, and we're going and hoping that we can maintain some level of the efficacy, but avoiding these very serious immune-related adverse events. We're not doing that yet because we're not seeing these sort of immune-related adverse events with our other costims. And the other very, very important thing, just to remind you from our preclinical modeling, these types of immune-related adverse events that we're seeing with the PSMA in combination -- costim in combination with Libtayo, are not seen preclinically when you combine with the CD3 bispecific.

因此，我們正在放棄全劑量組合，我們希望能夠保持一定程度的療效，但避免這些非常嚴重的免疫相關不良事件。我們還沒有這樣做，因為我們沒有在其他藥物中看到此類與免疫相關的不良事件。另一件非常非常重要的事情，只是為了提醒您，從我們的臨床前模型來看，我們在PSMA 組合（costim 與Libtayo 組合）中看到的這些類型的免疫相關不良事件，在臨床前並沒有觀察到。與 CD3 雙特異性結合。

And so we are very aggressively trying to move forward those programs as well, where we hope we may even have a better efficacy safety profile. So it's both a very exciting time to have these very active molecules.

因此，我們也非常積極地努力推進這些計劃，我們希望我們甚至可以擁有更好的功效安全性。因此，擁有這些非常活躍的分子是一個非常令人興奮的時刻。

Remember, I remind you, we have three classes now, three independent classes of very active molecules that have been individually validated in our portfolio. We have the checkpoint inhibitors, in particular, our PD-1 and our LAG-3 checkpoint inhibitors, which are validated. We have our CD3 bispecifics were validated, and we now have our costims, which are validated from the efficacy perspective. Very exciting time to be mixing and matching them. The challenge is to mix and match them appropriately to maximize the signal to noise, the therapeutic benefit relative to the potential adverse events we would see in the patients.

請記住，我提醒您，我們現在有三類，三類獨立的非常活躍的分子，這些分子已在我們的產品組合中單獨驗證。我們擁有經過驗證的檢查點抑製劑，特別是 PD-1 和 LAG-3 檢查點抑製劑。我們已經驗證了 CD3 雙特異性抗體，現在我們有了從功效角度驗證的 costim。混合和匹配它們是非常令人興奮的時刻。挑戰在於適當地混合和匹配它們，以最大化信噪比，即相對於我們在患者身上看到的潛在不良事件的治療益處。

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

我們的下一個問題來自 Salveen Richter 與高盛的對話。

And nice updates this morning. Clearly, the possibility of a permanent J code now has moved to April, and it shortens the runway for patients switching from EYLEA ahead of potentially loss of exclusivity in May. So kind of a 2-part question here. What are the dynamics around this? And how do you, on one hand, kind of maintain and grow the switch population from EYLEA. But secondly, how should we think about the uptake of high-dose area without a permanent J code?

今天早上的更新也不錯。顯然，永久 J 代碼的可能性現在已移至 4 月，並且它縮短了患者在 5 月可能失去排他性之前從 EYLEA 轉換的跑道。這是一個由兩部分組成的問題。這方面的動態是什麼？一方面，您如何維持和增長 EYLEA 的轉換群體。但其次，在沒有永久J代碼的情況下，我們應該如何考慮高劑量區域的攝取？

Hi Salveen. I'll get started. Certainly, we're conscious of the dates and the requirement for submissions to CMS that occur at the start of a quarter. we would estimate potentially the time frame that you're referencing, if we have an approval in the third quarter. What I would share is that we anticipate use of aflibercept 8-milligram after approval and launch before we have the permanent J code. Retina specialists are sophisticated in their reimbursement capabilities at the office level. They are experienced with newer products coming into the marketplace on a fairly regular basis. and how to make certain that they validate reimbursement for products prior to having the permanent J code under a temporary J code.

嗨薩爾文。我要開始了。當然，我們了解季度初向 CMS 提交的日期和要求。如果我們在第三季度獲得批准，我們可能會估計您所參考的時間範圍。我想分享的是，我們預計在獲得永久 J 代碼之前，我們預計會在獲得批准並推出後使用 8 毫克阿柏西普。視網膜專家在辦公室層面的報銷能力非常成熟。他們對定期進入市場的新產品有著豐富的經驗。以及如何確保他們在臨時 J 代碼下使用永久 J 代碼之前驗證產品的報銷。

So obviously, we want to have the permanent J code that will be a positive. But certainly, we do see the opportunity for uptake across patient types prior to that situation with CMS.

顯然，我們希望擁有永久的 J 代碼，這將是積極的。但當然，在 CMS 出現這種情況之前，我們確實看到了跨患者類型採用的機會。

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

我們的下一個問題來自特倫斯·弗林與摩根士丹利的對話。

Len, I know we've talked about this before, but the company has been somewhat nontraditional on pricing decisions historically. You guys priced EYLEA at a discount to Lucentis. You worked with ICER on DUPIXENT pricing. So just wondering why we shouldn't expect it similar approach here with high-dose EYLEA.

Len，我知道我們之前已經討論過這個問題，但該公司在定價決策方面歷來有些非傳統。你們給 EYLEA 的定價比 Lucentis 有折扣。您與 ICER 合作制定 DUPIXENT 定價。所以只是想知道為什麼我們不應該期望高劑量 EYLEA 也能採用類似的方法。

Thanks, Terence. If your comments referencing similar, I mean, thoughtful and appropriate, we would agree.

謝謝，特倫斯。如果您的評論提到類似，我的意思是，深思熟慮且適當，我們會同意。

Our next question comes from the line of Brian Abrahams with RBC Capital Markets.

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

Congrats on all the progress and appreciate all the details. Maybe just another clarification on 8-milligram aflibercept. Can you characterize your level of confidence that a reinspection would not be required? Have you had any interactions or feedback with the agency around this? And is there a defined period of time where the FDA would need to wait reinspection or not to ensure that the remediations are sustainable before approving the BLAs?

祝賀所有的進展並欣賞所有的細節。也許只是對 8 毫克阿柏西普的另一個澄清。您能否描述一下您對不需要重新檢查的信心程度？您是否與該機構就此進行過任何互動或反饋？在批准 BLA 之前，FDA 是否需要等待重新檢查或不需要等待一段明確的時間，以確保補救措施是可持續的？

Great. Thanks for your question. Well, we've tried to be 1,000% transparent as usual at Regeneron. And this is really let me just see if I can summarize it again, what we know. We've been in close contact with the FDA as has Catalent. We know what the remediations required are, and we've been submitting them on a rolling basis.

偉大的。謝謝你的提問。嗯，在 Regeneron，我們像往常一樣努力做到 1,000% 透明。這真的讓我看看我是否可以再次總結一下我們所知道的。我們和康泰倫特一樣一直與 FDA 保持密切聯繫。我們知道需要採取哪些補救措施，並且我們一直在滾動提交這些補救措施。

We expect to submit the last requirement by the middle of August, and that will be several days before the PDUFA date for the pozelimab BLA. The FDA has been very clear that they will strive to expeditiously review that. If they can, great, it can't. They said there would be a 3-month clock extension. But even with the 3-month clock extension, they've been very categorical in saying that they would prioritize their review and try and get it done as soon as possible.

我們預計在 8 月中旬之前提交最後一份要求，這將是 pozelimab BLA 的 PDUFA 日期前幾天。 FDA 已經非常明確地表示，他們將努力迅速對此進行審查。如果他們能，那就太好了，但不能。他們說時鐘會延長三個月。但即使延長了 3 個月的時間，他們也非常明確地表示，他們將優先考慮審核並儘力盡快完成。

Those facts are what led us to believe it would be done during the third quarter. In all of this is the fact that there has been no need, no discussion, no indication whatsoever that a reinspection would be necessary.

這些事實使我們相信這將在第三季度完成。在所有這一切中，事實是沒有必要、沒有討論、也沒有任何跡象表明有必要進行重新檢查。

The FDA, of course, is free to make those decisions but we have not seen any indication of that in our very detailed and close contact. So we've given you our best estimate at this point.

當然，FDA 可以自由地做出這些決定，但我們在非常詳細和密切的接觸中沒有看到任何跡象。所以我們目前已經給了您最好的估計。

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

我們的下一個問題來自摩根大通的克里斯·肖特（Chris Schott）。

Can I just come back to the CD28 PSMA update. Maybe just elaborate a little bit more in terms of the approach of lowering the PD-1 exposure to address the safety issues here and taking that approach versus trying to work to further adjust the dosing of the bispecific piece of the equation?

我可以回到 CD28 PSMA 更新嗎？也許只是詳細說明一下降低 PD-1 暴露的方法以解決這裡的安全問題，並採取該方法而不是試圖進一步調整等式中雙特異性部分的劑量？

Well, we should say that we are adjusting both doses. We have been already exploring a variety of doses from very low doses to the highest active doses on the costim side, but we've been doing all of them in the context of the full dose of Libtayo.

好吧，我們應該說我們正在調整這兩種劑量。我們已經在 costim 方面探索了從極低劑量到最高活性劑量的各種劑量，但我們一直在 Libtayo 全劑量的背景下進行所有這些劑量。

So now what we're doing is we're exploring some of the doses that are active particularly ones that are active as monotherapy, as I mentioned, there is monotherapy activity with the PSMA costim and now were to try to decrease these immune-related adverse events.

因此，現在我們正在做的是，我們正在探索一些有效的劑量，特別是作為單一療法有效的劑量，正如我提到的，PSMA costim 具有單一療法活性，現在我們要嘗試減少這些與免疫相關的劑量。不良事件。

Let me remind you, they are in the same sort of class of immune-related adverse events that you do see with checkpoint inhibitors in general. We're just seeing them in some patients, the one with the biggest responses, in some cases to a greater extent.

讓我提醒您，它們與您在一般檢查點抑製劑中看到的免疫相關不良事件屬於同一類。我們只是在一些患者身上看到了它們，這些患者是反應最大的患者，在某些情況下反應程度更大。

So we're hoping that lowering the checkpoint inhibition may allow us to adjust the therapeutic window there. But we are, as you're saying, dealing with a couple of different doses of the costim, but now we're incorporating lower doses of the Libtayo into the program as well.

因此，我們希望降低檢查點抑制可以讓我們調整那裡的治療窗口。但正如您所說，我們正在處理幾種不同劑量的 costim，但現在我們也將較低劑量的 Libtayo 納入該計劃。

I think what George said earlier, and just maybe Bayer's repeating is that he said that we're starting with the good position of having very impressive efficacy, one and two, side effects that are for the most part in the patients who are benefiting with the efficacy. That's a very good position to begin to explore and how to get the therapeutic index or signal to noise, as George called it right.

我認為喬治早些時候所說的，也許拜耳重複的是，他說我們一開始就具有非常令人印象深刻的功效，一和兩個副作用，這些副作用大部分發生在受益於的患者身上。的功效。這是一個非常好的位置，可以開始探索如何獲得治療指數或信噪比，正如喬治所說的那樣。

Our next question comes from the line of Dane Leone with Raymond James.

我們的下一個問題來自戴恩·利昂 (Dane Leone) 和雷蒙德·詹姆斯 (Raymond James) 的對話。

Congratulations on the updates and best of luck with the resolution of the reviews for pozelimab and 8 megs aflibercept. I actually want to ask you to expand a bit on your discussions with the FDA and potential filing or early filing on DUPIXENT for COPD. The point I'd like a little bit more clarity on is specifically what you may be able to have from notice before the final readout of that study that you could potentially include in a package with the BOREAS results to get the FDA comfortable with an accelerated review for that indication?

祝賀更新，祝您好運，解決 pozelimab 和 8 megs aflibercept 的評論。實際上，我想請您詳細介紹一下您與 FDA 的討論以及 DUPIXENT 治療 COPD 的潛在申請或早期申請。我想更清楚地說明一點是，在該研究最終讀出之前，您可以從通知中獲得什麼，您可以將其與 BOREAS 結果一起包含在一個包中，以使 FDA 對加速加速感到滿意。審查該指示？

Yes. What we know right now is that we're going to need data from notice. And right now, as we said, we are still in discussions on what that data could be. And so right now, we don't have any details to give you.

是的。我們現在知道的是，我們將需要來自通知的數據。現在，正如我們所說，我們仍在討論這些數據可能是什麼。所以現在我們沒有任何細節可以向您提供。

Our next question comes from the line of Colin Bristow with UBS.

我們的下一個問題來自瑞銀集團的 Colin Bristow。

Congrats on the quarter and on the progress. Just maybe one on the itepekimab interim. Can you share anything on the futility thresholds? And if not specifically, then could you say how it sort of fared relative to BOREAS?

祝賀本季度和取得的進展。也許只是 itepekimab 臨時藥物中的一個。您能分享一些關於無用閾值的信息嗎？如果不是具體的話，那麼你能說說它相對於 BOREAS 的表現如何嗎？

I don't think we have anything specific. This was (inaudible) -- by the Data Safety Monitoring Committee, sort of a standard approach. We're pleased that we passed it. And we will look forward to further data at the end of the study.

我認為我們沒有什麼具體的內容。這是（聽不清）——由數據安全監測委員會制定，是一種標準方法。我們很高興我們通過了它。我們將期待研究結束時獲得更多數據。

Yes. And both we and Sanofi are blinded to that. We only got the go decision from the independent data monitoring committee. So we'll proceed to a final readout for both of those studies.

是的。我們和賽諾菲都對此視而不見。我們只得到了獨立數據監測委員會的決定。因此，我們將繼續對這兩項研究進行最終解讀。

Our next question comes from the line of Brian Shane with Baird.

我們的下一個問題來自 Brian Shane 和 Baird 的對話。

This is Luke on for Brian. Can you just provide a little bit more color on what drove the Libtayo growth this quarter? Was there any stocking? Or was it largely demand-based?

這是盧克為布萊恩代言的。您能否提供更多關於推動 Libtayo 本季度增長的因素？有沒有長筒襪？或者它很大程度上是基於需求的？

Luke, and I'm pleased to share it is demand growth. Certainly, we see continued and steady performance across our skin indications, both cutaneous squamous cell carcinoma and basal cell carcinoma -- in addition to that, it is exciting that we are seeing not only an increase in the number of prescribers for our lung cancer indications, but the depth of prescribing is improving and increasing in both the community and also academic settings. -- that is demand based, it is not stocking based.

盧克，我很高興與大家分享這就是需求增長。當然，我們看到皮膚適應症（皮膚鱗狀細胞癌和基底細胞癌）持續穩定的表現——除此之外，令人興奮的是我們不僅看到肺癌適應症的處方者數量增加，但在社區和學術環境中，處方的深度正在改善和增加。 ——這是基於需求的，而不是基於庫存的。

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

我們的下一個問題來自 Leerink Partners 的 David Risinger。

So my question is for George on the costims, please. You mentioned that you haven't seen the immune as with respect to your other Costim trials. Could you please comment on whether the dosing step-ups at this point are close to the higher dosing levels that you're stepping back from in the PSMA trial. I'm just trying to contextualize whether you really have advanced those other trials to the point to really know whether you're going to have similar problems in your other Costim trials?

我想問喬治關於服裝的問題。您提到您沒有看到與其他 Costim 試驗一樣的免疫效果。您能否評論一下此時的劑量增量是否接近您在 PSMA 試驗中退出的較高劑量水平。我只是想了解一下您是否真的已經將其他試驗推進到真正了解您在其他 Costim 試驗中是否會遇到類似問題的程度？

That's a very good and fair question. And those programs are at earlier stages. So we won't know until we're more advanced, whether when we get to the same sort of efficacy type levels, do we have the same sort of immune-related adverse event associations or not? What I was referring to is in the preclinical studies, the amount of this associated T cell activation that can lead to these sorts of immune-related adverse events varies depending on the tumor class and on the costim in itself.

這是一個非常好的、公平的問題。這些計劃還處於早期階段。因此，直到我們更先進時，我們才會知道，當我們達到相同的功效類型水平時，我們是否會出現相同類型的免疫相關不良事件關聯？我指的是在臨床前研究中，可能導致這些類型的免疫相關不良事件的相關 T 細胞激活量因腫瘤類別和 costim 本身而異。

So based on that, we would expect to see different ratios of immune-related adverse events. Those other programs, though right now are all in stages where they were in a full dose Libtayo combinations at this point.

因此，基於此，我們預計會看到不同比例的免疫相關不良事件。這些其他項目目前都處於全劑量 Libtayo 組合的階段。

Our last question is from Akash Tewari with Jefferies.

我們的最後一個問題是來自 Jefferies 的 Akash Tewari。

I'll switch it up. I guess maybe for your obesity program, you had data at the ADA showing synergy with your[mayostatin] inhibition program when combined with the GLP-1 I guess the natural observation here is Regeneron doesn't currently have a program in development. Is there any interest in acquiring one externally via BB or partnership at this time?

我會切換它。我想也許對於您的肥胖計劃，您在ADA 的數據顯示，當與GLP-1 結合時，您的[mayostatin] 抑制計劃具有協同作用，我想這裡的自然觀察結果是再生元目前沒有正在開發的計劃。目前是否有興趣通過 BB 或合作夥伴方式從外部收購一台？

Well, what we would say is we do think that, obviously, there's a lot of focus on obesity and particularly these new agents that are causing a large amount of weight loss. But as you described as being increasingly recognized that the quality of this weight loss may prove challenging that many patients are actually losing muscle or lean body mass which is -- can be very detrimental, particularly if they stay on these therapies or yoyo on and off them.

好吧，我們想說的是，我們確實認為，顯然，人們對肥胖有很多關注，特別是這些導致體重大量減輕的新藥物。但正如您所描述的那樣，人們越來越認識到這種減肥的質量可能具有挑戰性，許多患者實際上正在失去肌肉或瘦體重，這可能非常有害，特別是如果他們堅持這些療法或斷斷續續地進行溜溜球他們。

That can really lead to substantial changes over time and body composition and can be very debilitating for patients. And as you said, we've had a long investment in programs that can maintain muscle mass in various settings and we've shown that they can maintain or even grow muscle mass in the setting of these types of obesity treatments in our preclinical modeling.

隨著時間的推移，這確實會導致身體成分發生巨大變化，並且可能使患者非常虛弱。正如您所說，我們對可以在各種環境下維持肌肉質量的項目進行了長期投資，並且我們已經在臨床前模型中證明，它們可以在這些類型的肥胖治療環境下維持甚至增加肌肉質量。

So obviously, it is a very exciting opportunity to think about, which is can we combine some of our muscle preservation or growth strategies and biologics to prevent these concerning side effects that are being seen with the new class of profound weight loss agents.

顯然，這是一個非常令人興奮的思考機會，我們是否可以將一些肌肉保存或生長策略與生物製劑結合起來，以防止新型深遠減肥劑所出現的副作用。

And so we are very actively pursuing everything that we can imagine and hopefully, we'll be providing updates on our approaches as time goes along.

因此，我們非常積極地追求我們能想像到的一切，希望隨著時間的推移，我們將提供我們方法的更新。

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

好的。謝謝喬治，感謝今天撥通電話的所有人以及您對再生元的興趣。我們向那些留在隊列中但沒有機會收到消息的人表示歉意。與往常一樣，投資者關係團隊可以回答任何剩餘問題。再次感謝您，祝您有美好的一天。

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

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連接。