雷傑納榮製藥 (REGN) 2023 Q3 法說會逐字稿

Welcome to the Regeneron Pharmaceuticals Third Quarter 2023 Earnings Conference Call. My name is Shannon, and I will be your operator for today's call.

歡迎參加再生元製藥 2023 年第三季財報電話會議。我叫香農，我是今天電話的接線生。

(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.

（操作員說明）請注意，本次會議正在錄製中。我現在將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 third quarter 2023 earnings conference call. An archive and transcript of this webcast will be available on our Investor Relations website shortly after the call ends.

謝謝你，香農。世界各地的聽眾早安、下午好、晚上好。感謝您對 Regeneron 的關注，歡迎參加我們的 2023 年第三季財報電話會議。通話結束後不久，我們的投資者關係網站將提供該網路廣播的檔案和文字記錄。

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

與我一起參加今天電話會議的還有董事會聯合主席、聯合創始人、總裁兼首席執行官 Leonard Schleifer 博士； George Yancopoulos 博士，董事會聯合主席、共同創辦人、總裁兼首席科學官； Marion McCourt，執行副總裁兼商務主管；和鮑勃·蘭德里，執行副總裁兼財務長。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 about Regeneron. Such statements may include, but are not limited to those related to Regeneron and its products and businesses -- business, financial forecast and guidance, revenue diversification, development programs and related anticipated milestones, collaborations, financial and competition. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-Q for the quarterly period ended September 30, 2023, which was filed with the SEC this morning.

我想提醒您，今天電話會議的言論可能包括有關再生元的前瞻性陳述。此類聲明可能包括但不限於與再生元及其產品和業務相關的聲明—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、合作、財務和競爭。每項前瞻性陳述都存在風險和不確定性，可能導致實際結果和事件與該陳述中的預測有重大差異。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 9 月 30 日的季度報告 10-Q 表格。

Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

再生元不承擔任何更新任何前瞻性陳述的義務，無論是由於新資訊、未來事件或其他原因。

In addition, please note that GAAP and non-GAAP measures will be discussed in today's call. Information regarding our use of non-GAAP financial measures and a reconciliation of those measures to GAAP is available in our financial results press release and our corporate presentation, both of which can be accessed on our website. Once our call concludes, Bob Landry and the Investor Relations team will be available to answer any further questions.

此外，請注意，今天的電話會議將討論公認會計原則和非公認會計原則措施。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，兩者都可以在我們的網站上訪問。在我們的電話會議結束後，鮑勃·蘭德里和投資者關係團隊將可以回答任何進一步的問題。

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

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

Thanks, Ryan, and thanks to everyone joining today's call. Regeneron delivered another strong quarter marked by continued execution across the company, which drove double-digit top line growth and notable progress across our innovative R&D pipeline. Total revenues increased by 15% on a reported basis compared to the prior year quarter, primarily driven by Sanofi collaboration revenues and LIBTAYO global net product sales, which grew by 50% and 62%, respectively. Dupixent global net product sales were $3.1 billion, up 33%, reflecting strong growth across all approved indications.

謝謝瑞安，也謝謝參加今天電話會議的所有人。再生元公司又迎來了一個強勁的季度，整個公司的持續執行力推動了兩位數的營收成長，並在我們的創新研發管道上取得了顯著進展。與去年同期相比，總收入成長了 15%，這主要是由賽諾菲合作收入和 LIBTAYO 全球產品淨銷售額分別成長 50% 和 62% 推動的。 Dupixent 全球產品淨銷售額為 31 億美元，成長 33%，反映出所有核准適應症的強勁成長。

Non-GAAP net income per share -- diluted share increased by 4%, including an unfavorable $0.77 impact from acquired IPR&D.

非 GAAP 每股淨利潤－稀釋後每股收益成長 4%，其中包括收購的 IPR&D 帶來的 0.77 美元不利影響。

Today, I will briefly discuss the launch of EYLEA HD, the progress we continue to make across our pipeline, and our latest thinking on capital allocation. I will then hand the call over to George, Marion and Bob, who will provide additional commentary on our pipeline, developments, commercial execution and our financial results for the quarter.

今天，我將簡要討論 EYLEA HD 的推出、我們在管道上繼續取得的進展，以及我們對資本配置的最新思考。然後，我會將電話轉交給喬治、馬里昂和鮑勃，他們將對我們的管道、開發、商業執行和本季度的財務業績提供更多評論。

Starting with EYLEA HD, which is off to a great start. We launched in late August shortly following FDA approval, and recorded $43 million of net product sales in the final 6 weeks of the quarter, which compares favorably to recent launches in the retinal disease category. Importantly, revenues were driven by strong initial demand with multiple reorders by distributors before the end of the quarter.

從 EYLEA HD 開始，這是一個好的開始。我們在 FDA 批准後不久於 8 月下旬推出，並在本季最後 6 週內錄得 4,300 萬美元的產品淨銷售額，這與最近推出的視網膜疾病類別相比相當不錯。重要的是，收入是由強勁的初始需求推動的，分銷商在本季度末之前多次重新訂購。

In addition, samples for EYLEA HD were made available shortly after the launch, enabling prescribers and patients to trial the product. Early EYLEA HD utilization has come from across the spectrum of wet age-related macular degeneration and diabetic macular edema patients, and momentum continues to build as positive real-world clinical experiences accumulate.

此外，EYLEA HD 的樣品在推出後不久就提供了，使處方者和患者能夠試用該產品。 EYLEA HD 的早期應用來自濕性老年黃斑部病變和糖尿病黃斑水腫患者，隨著積極的現實臨床經驗的積累，這種勢頭不斷增強。

We have also made significant progress establishing access and reimbursement, and we will continue to work on positioning EYLEA HD, the highest dose anti-VEGF therapy approved by the FDA, as a new standard of care in these retinal diseases.

我們在存取和報銷方面也取得了重大進展，我們將繼續致力於將 EYLEA HD（FDA 批准的最高劑量抗 VEGF 療法）定位為這些視網膜疾病的新護理標準。

Moving on to the recent progress we have made advancing our pipeline. Within hematology oncology, in our CD3 bispecific platform, the BLA for odronextamab, our CD20xCD3 bispecific in certain lymphomas, was accepted by the FDA and granted priority review, which are -- with a March 31 PDUFA data assigned. We also remain on track to submit a BLA next month for linvoseltamab, our BCMAxCD3 bispecific for multiple myeloma, with pivotal trials now underway for both programs to support potential accelerated approvals, we are preparing for 2 commercial launches next year.

接下來是我們最近在推進管道方面的進展。在血液腫瘤學領域，在我們的CD3 雙特異性平台中，odronextamab（我們在某些​​淋巴瘤中的CD20xCD3 雙特異性藥物）的BLA 已被FDA 接受並獲得優先審查，並分配了3 月31 日的PDUFA 數據。我們還有望在下個月提交linvoseltamab 的BLA，這是我們針對多發性骨髓瘤的BCMAxCD3 雙特異性藥物，目前這兩個項目正在進行關鍵試驗，以支持潛在的加速批准，我們正在為明年的兩次商業上市做準備。

Last week, we reported a potential breakthrough for patients with profound congenital hearing loss. The first patient enrolled in the Phase I/II CHORD clinical trial of DB-OTO, an investigational cell selective adenovirus associated viral gene therapy designed to provide durable physiological hearing to individuals with profound congenital hearing loss caused by mutations in the otoferlin gene, experienced hearing improvement 6 weeks after treatment compared to baseline. We are looking forward to continued follow-up with this patient as well as enrollment of additional patients to further validate this gene therapy approach.

上週，我們報告了針對嚴重先天性聽力損失患者的潛在突破。第一位參與DB-OTO I/II 期CHORD 臨床試驗的患者，DB-OTO 是一種研究性細胞選擇性腺病毒相關病毒基因療法，旨在為因otoferlin 基因突變引起的嚴重先天性聽力損失的個體提供持久的生理聽力。與基線相比，治療後 6 週有所改善。我們期待繼續對該患者進行隨訪，並招募更多患者，以進一步驗證這種基因治療方法。

While otoferlin gene deficiency is an ultra-rare condition, we are hopeful that we can expand our approach to gene therapy in the year to more common genetic causes of profound hearing loss.

雖然耳鐵蛋白基因缺陷是一種極為罕見的疾病，但我們希望今年能夠將基因治療方法擴展到導致嚴重聽力損失的更常見的遺傳原因。

Finally, regarding capital allocation. While we continue to prioritize internal R&D investment, given the strength of our balance sheet and anticipated future cash flows, we believe we have the flexibility to take additional actions to drive shareholder value. Beyond our ongoing share repurchase program, we continue to actively pursue emerging science and innovative platforms that complement our core R&D strengths.

最後，關於資本配置。雖然我們繼續優先考慮內部研發投資，但考慮到我們的資產負債表實力和預期的未來現金流，我們相信我們可以靈活地採取額外行動來推動股東價值。除了我們正在進行的股票回購計劃之外，我們還繼續積極尋求新興科學和創新平台，以補充我們的核心研發優勢。

In addition to the Decibel acquisition, we announced last month an expanded research collaboration with Intellia combining our proprietary antibody targeted viral vector delivery technologies with Intellia's CRISPR platform to jointly explore in vivo programs outside of the liver for neurological and muscular diseases.

除了收購Decibel 之外，我們上個月還宣布擴大與Intellia 的研究合作，將我們專有的抗體靶向病毒載體遞送技術與Intellia 的CRISPR 平台相結合，共同探索肝臟以外神經和肌肉疾病的體內項目。

We have always managed Regeneron with a focus on generating long-term returns, and we will continue to think carefully about how to strategically deploy our capital, with the goal of delivering breakthroughs to patients and value to shareholders.

我們管理再生元一直注重創造長期回報，我們將繼續仔細思考如何策略性地部署我們的資本，目標是為患者帶來突破，為股東帶來價值。

In closing, we had a strong third quarter, the EYLEA HD launch is progressing well, our pipeline is delivering important innovations, and we continue to look at ways to efficiently allocate capital.

最後，我們的第三季表現強勁，EYLEA HD 的推出進展順利，我們的產品線正在提供重要的創新，我們將繼續尋找有效分配資本的方法。

With that, let me turn the call over to George.

現在，讓我把電話轉給喬治。

Thanks, Len. I'd like to start with our recent data update for EYLEA HD. At the EURETINA Meeting last month, we presented the 2-year results from the PULSAR study in wet AMD, which demonstrated that the vast majority of EYLEA HD patients randomized to 12- and 16-week dosing intervals continue to sustain vision and anatomic improvements through 96 weeks. 78% of all EYLEA HD patients were able to maintain at least every 12-week dosing intervals for the entire 2-year period, with 88% assigned to at least every 12-week dosing by the end of the 2-year period.

謝謝，萊恩。我想從我們最近的 EYLEA HD 數據更新開始。在上個月的EURETINA 會議上，我們展示了濕性AMD 的PULSAR 研究的2 年結果，該結果表明，絕大多數EYLEA HD 患者隨機接受12 週和16 週的給藥間隔，透過以下方式繼續維持視力和解剖學改善： 96 週。所有 EYLEA HD 患者中的 78% 能夠在整個 2 年期間維持至少每 12 週給藥一次，其中 88% 的患者在 2 年期結束時至少每 12 週給藥一次。

Similarly, 70% of patients randomized to every 16-week dosing at baseline we're able to maintain at least that interval through 2 years with 78% assigned to at least every 16-week dosing at week 96. Moreover, during the second year, many patients met the criteria for extension to even longer dosing intervals, with 47% meeting the criteria for at least 20-week dosing intervals, including 28% who were eligible for 24-week dosing equals.

同樣，70% 的患者在基線時被隨機分配到每16 週給藥一次，我們能夠在2 年內至少維持該間隔，其中78% 的患者在第96 週被分配到至少每16 週給藥一次。此外，在第二年許多患者符合延長給藥間隔的標準，其中 47% 符合至少 20 週給藥間隔的標準，其中 28% 符合 24 週給藥間隔的標準。

The safety profile of EYLEA HD remain consistent with EYLEA, sustaining vision and anatomic improvements while maintaining such extended dosing intervals over 2 years in both wet AMD and DME is a remarkable advancement for the patients and their physicians. We believe that these results give EYLEA HD the potential to become the new standard of care for these retinal diseases.

EYLEA HD 的安全性與 EYLEA 保持一致，在濕性 AMD 和 DME 中維持視力和解剖學改善，同時維持如此延長的給藥間隔超過 2 年，這對患者及其醫生來說是一個顯著的進步。我們相信這些結果使 EYLEA HD 有可能成為這些視網膜疾病的新護理標準。

Moving to our immunology and inflammation pipeline. On Dupixent in COPD, our first pivotal study BOREAS met the primary and all 2 secondary endpoints in a previously unprecedented success for a biologic in a Phase III study in patients with uncontrolled COPD and evidence of type 2 inflammation. Based on recent feedback from the FDA, in addition to the positive results from the BOREAS study, a positive interim analysis of the replicate Phase III NOTUS study would enable an sBLA submission. The independent data monitoring committee will conduct an interim analysis of the NOTUS study later this year.

轉向我們的免疫學和發炎管道。在Dupixent 治療COPD 上，我們的第一項關鍵研究BOREAS 達到了主要終點和所有2 個次要終點，在針對未受控制的COPD 和2 型發炎證據的患者進行的III 期研究中，生物製劑取得了前所未有的成功。根據 FDA 最近的回饋，除了 BOREAS 研究的積極結果外，對複製 III 期 NOTUS 研究的積極中期分析也將有助於提交 sBLA。獨立數據監測委員會將於今年稍後對 NOTUS 研究進行中期分析。

For itepekimab, our anti-IL-33 antibody, the Phase III AERIFY-1 and 2 studies remain on track for readout and potential regulatory submissions in 2025, both itepekimab and Dupixent could transform the treatment paradigm for COPD by leveraging their distinct mechanisms of actions in reducing different types of inflammation that contribute to COPD disease progression, and we look forward to the results of these studies.

對於 itepekimab（我們的抗 IL-33 抗體），III 期 AERIFY-1 和 2 研究仍有望在 2025 年進行讀數和潛在的監管提交，itepekimab 和 Dupixent 都可以利用其獨特的作用機制改變 COPD 的治療模式減少導致慢性阻塞性肺病疾病進展的不同類型的炎症，我們期待這些研究的結果。

Moving to oncology and combination with Libtayo. We remain on target and are currently enrolling our pivotal study of Libtayo combined with our LAG-3 antibody, fianlimab, in first-line metastatic melanoma. We believe this combination may provide a significant advance for patients in this setting based on our encouraging earlier-stage studies. At the annual ESMO meeting, we presented data from the Phase II trial of neoadjuvant Libtayo treatment for resectable cutaneous squamous cell carcinoma or CSCC, which demonstrated event-free survival for the vast majority, 89% of the patients at 1 year.

轉向腫瘤學並與 Libtayo 合併。我們仍然堅持目標，目前正在進行 Libtayo 與我們的 LAG-3 抗體 fianlimab 聯合治療一線轉移性黑色素瘤的關鍵研究。根據我們令人鼓舞的早期研究，我們相信這種組合可能會為這種情況下的患者帶來重大進步。在年度 ESMO 會議上，我們展示了新輔助 Libtayo 治療可切除皮膚鱗狀細胞癌或 CSCC 的 II 期試驗數據，該試驗證明絕大多數患者（89%）的 1 年無事件生存率。

It is also noteworthy that of the 51% of patients who had a pathological complete response, none have since experienced disease recurrence. These results add to the growing body of evidence of Libtayo and other checkpoint inhibitors may have utility in earlier stages of CSCC and other malignancies. To further explore this, we are conducting a Libtayo trial in adjuvant CSCC for patients at heightened risk. We're also evaluating the combination of the Libtayo and fianlimab in adjuvant melanoma, and plan to initiate a study of this combination in the perioperative melanoma setting as well.

另外值得注意的是，在 51% 獲得病理學完全緩解的患者中，沒有人出現疾病復發。這些結果為 Libtayo 和其他檢查點抑制劑可能在 CSCC 和其他惡性腫瘤的早期階段發揮作用提供了越來越多的證據。為了進一步探討這一點，我們正在針對高風險患者進行輔助性 CSCC 的 Libtayo 試驗。我們也正在評估 Libtayo 和 fianlimab 聯合治療黑色素瘤的輔助治療，並計劃在圍手術期黑色素瘤中啟動此聯合治療的研究。

On to bispecifics. First in hematology/oncology. We are pleased that odronextamab, our CD20xCD3 bispecific, was recently accepted for review by both the FDA and European regulatory authorities in relapsed/refractory follicular lymphoma and diffuse large B-cell lymphoma. Based on the pivotal Phase II data from the ELM-2 study, we have initiated a robust OLYMPIA Phase III development program, investigating odronextamab as monotherapy as well as in combination with current standards of care in earlier lines of follicular lymphoma and DLBCL. We are looking forward to the pivotal data presentations from ELM-2 later this year.

關於雙特異性。首先是血液學/腫瘤學。我們很高興我們的 CD20xCD3 雙特異性藥物 odronextamab 最近被 FDA 和歐洲監管機構接受審查，用於治療復發/難治性濾泡性淋巴瘤和瀰漫性大 B 細胞淋巴瘤。基於 ELM-2 研究的關鍵 II 期數據，我們啟動了一項強有力的 OLYMPIA III 期開發計劃，研究 odronextamab 作為單一療法以及與當前濾泡性淋巴瘤和 DLBCL 早期治療標準的結合。我們期待今年稍後 ELM-2 的關鍵數據演示。

We're also on track to submit our regulatory application for linvoseltamab our BCMAxCD3 antibody for relapsed/refractory multiple myeloma by the end of the year. This bispecific may potentially offer best-in-class efficacy and convenience. The LINKER-MM3 confirmatory Phase III study (inaudible) linvoseltamab monotherapy compared to a standard of care regimen is enrolling and studies in earlier lines of multiple myeloma and other plasma cell diseases will be enrolling soon.

我們也預計在今年年底前提交 linvoseltamab 的監管申請，我們的 BCMAxCD3 抗體用於治療復發/難治性多發性骨髓瘤。這種雙特異性藥物可能提供一流的功效和便利性。與標準護理方案相比的 LINKER-MM3 驗證性 III 期研究（聽不清楚）linvoseltamab 單一療法正在招募，針對多發性骨髓瘤和其他漿細胞疾病早期系列的研究也將很快招募。

Finally, in addition to the ongoing Phase I combination study of odronextamab in our CD22xCD20 co-stimulatory bispecific, we're also on track to initiate a study of linvoseltamab with a corresponding costimulatory bispecific next year.

最後，除了正在進行的 odronextamab 在我們的 CD22xCD20 共刺激雙特異性藥物中的 I 期聯合研究之外，我們還計劃明年啟動 linvoseltamab 與相應的共刺激雙特異性藥物的研究。

Next, on to bispecifics for solid tumors, which are being investigated in combination with Libtayo and other modalities. At ESMO, we shared initial clinical data for the combination of ubamatamab, our MUC16xCD3 bispecific with Libtayo in advanced ovarian cancer. In these early data, promising durable responses were observed with ubamatamab monotherapy as well as encouraging combination activity with Libtayo with evidence of turnaround responses after initial progression on monotherapy leading in multiple patients upon addition of the Libtayo.

接下來，關於實體瘤的雙特異性藥物，目前正在與 Libtayo 和其他方式結合進行研究。在 ESMO，我們分享了 ubamatamab（我們的 MUC16xCD3 雙特異性藥物）與 Libtayo 聯合治療晚期卵巢癌的初步臨床數據。在這些早期數據中，觀察到ubamatamab 單藥治療有希望的持久反應，並且與Libtayo 的聯合治療令人鼓舞，有證據表明，在添加Libtayo 後，多位患者在單藥治療初始進展後出現了好轉反應。

A randomized Phase II expansion study is ongoing to evaluate 2 active monotherapy doses of ubamatamab, with the lower dose also tested in combination with Libtayo in order to optimize dosing and evaluate the potential added activity of Libtayo. In addition, we're exploring ubamatamab in multiple rare cancers that are known to express high levels of MUC16.

正在進行一項隨機 II 期擴展研究，以評估 ubamatamab 的 2 個活性單藥治療劑量，同時也對較低劑量與 Libtayo 聯合進行測試，以優化劑量並評估 Libtayo 的潛在附加活性。此外，我們正在探索 ubamatamab 在多種已知表達高水平 MUC16 的罕見癌症中的作用。

In terms of our costimulatory bispecifics for solid tumors, we are currently exploring multiple different CD28 costimulatory bispecific antibodies in early clinical trials in a variety of tumor settings in combination with Libtayo with corresponding CD3 bispecifics.

就我們針對實體瘤的共刺激雙特異性抗體而言，我們目前正在各種腫瘤環境中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 和相應的CD3 雙特異性抗體的組合。

We are continuing development of our PSMAxCD28 co-stimulatory bispecific in advanced prostate cancer, focusing and identifying the window of opportunity for maintaining the remarkable antitumor activity observed this treatment while minimizing serious toxicity. In order to explore this, we have expanded enrollment in the PSMAxCD28 monotherapy cohort, and we'll soon initiate cohorts in which investigators will have an option of adding a low dose of cemiplimab to the PSMAxCD28 treatment in certain patients.

我們正在繼續開發用於晚期前列腺癌的 PSMAxCD28 共刺激雙特異性藥物，重點關注並確定維持這種治療所觀察到的顯著抗腫瘤活性的機會窗口，同時最大限度地減少嚴重毒性。為了探索這一點，我們擴大了 PSMAxCD28 單藥治療隊列的招募範圍，並且我們很快就會啟動隊列，研究人員可以選擇在某些患者的 PSMAxCD28 治療中添加低劑量的 cemiplimab。

Moreover, we plan to initiate a trial combining PSMA/CD28 with PSMA/CD3 since, based on preclinical data CD28 costims with appropriate CD3 bispecifics may yield antitumor activity without severe immune-mediated adverse events. We also hope to progress an additional prostate specific CD3 bispecific towards the clinic in the next year, which we may also combine with our PSMA costimulatory bispecific.

此外，我們計劃啟動一項將PSMA/CD28 與PSMA/CD3 結合的試驗，因為根據臨床前數據，CD28 與適當的CD3 雙特異性藥物的組合可能會產生抗腫瘤活性，而不會產生嚴重的免疫介導的不良事件。我們也希望明年將額外的前列腺特異性 CD3 雙特異性藥物推向臨床，我們也可能將其與我們的 PSMA 共刺激雙特異性藥物結合。

In terms of our MUC16xCD28 costim in combination with Libtayo in ovarian cancer, we are planning on presenting initial data by the end of the year. Regarding our EGFRxCD28 costim in combination with Libtayo, we are planning on presenting updated dose escalation data in 2024. We will soon commence enrollment across 8 tumor-specific expansion cohorts in the study, including colorectal cancer with or without liver metastasis, as well as EGFR mutant non-small cell lung cancer.

就我們的 MUC16xCD28 costim 與 Libtayo 聯合治療卵巢癌而言，我們計劃在今年年底前提供初步數據。關於我們的EGFRxCD28 costim 與Libtayo 組合，我們計劃在2024 年提供更新的劑量遞增數據。我們很快將開始在研究中招募8 個腫瘤特異性擴展隊列，包括伴或不伴肝轉移的結直腸癌，以及EGFR突變型非小細胞肺癌。

Now to genetic medicines. We and Intellia recently announced expansion of our research collaboration to include Regeneron's proprietary antibody target delivery technology, with the goal of expanding the reach of in vivo gene editing to neurological and muscle diseases. The aim of this expanded collaboration is to address a current bottleneck in genetic medicine, the inability to deliver genetic payload beyond the liver.

現在談談基因藥物。我們和 Intellia 最近宣布擴大我們的研究合作，納入 Regeneron 專有的抗體標靶遞送技術，目標是將體內基因編輯的範圍擴大到神經和肌肉疾病。這次擴大合作的目的是解決目前遺傳醫學的瓶頸，無法將遺傳有效負載傳遞到肝臟以外。

Our proprietary preclinically validated antibody-directed AAV approach will initially test 2 in vivo nonliver targets. Additionally, we and Intellia announced FDA clearance to start a pivotal Phase III trial of NTLA-2001 for the treatment of ATTR amyloidosis with cardiomyopathy. The first time in investigational in vivo CRISPR-based gene therapy editing is clear to enter a late-stage clinical development in the United States. The trial is expected to initiate by year-end 2023.

我們專有的臨床前驗證抗體導向 AAV 方法將首先測試 2 個體內非肝臟標靶。此外，我們和 Intellia 宣布 FDA 批准啟動 NTLA-2001 的關鍵 III 期試驗，用於治療 ATTR 澱粉樣變性心肌病變。首次在體內基於 CRISPR 的基因治療編輯研究顯然將在美國進入後期臨床開發。該試驗預計將於 2023 年底啟動。

Moving to our Alnylam collaboration. Alnylam recently presented updated interim ALN-APP data in early onset Alzheimer's disease. Updated data showed that single doses of ALN-APP achieved sustained robust reduction in APP alpha and APP beta measured in the CSF up to 10 months after administration, as well as reduction of amyloidogenic peptides implicated in Alzheimer's disease and cerebral amyloid angiopathy.

轉向我們的 Alnylam 合作。 Alnylam 最近發布了早發性阿茲海默症的最新中期 ALN-APP 數據。更新的數據顯示，單劑量的ALN-APP 在給藥後長達10 個月內實現了CSF 中APP α 和APP β 的持續強勁減少，以及與阿茲海默症和腦澱粉樣血管病變有關的澱粉樣勝肽的減少。

Alnylam has also announced that a first patient has been redosed with ALN-APP in the multi-dose portion of the study currently proceeding outside of the United States. We and Alnylam plan to initiate additional clinical programs for neurodegenerative diseases, including for amyotrophic lateral sclerosis next year.

Alnylam 也宣布，目前在美國境外正在進行的研究的多劑量部分中，第一位患者已重新接受 ALN-APP 治療。我們和 Alnylam 計劃明年啟動更多針對神經退化性疾病（包括肌萎縮側索硬化症）的臨床計畫。

Finally, I would like to highlight DB-OTO, our otoferlin gene therapy, Regeneron's first clinical program for genetic hearing loss, which we've developed over the last few years in collaboration with Decibel Therapeutics, a company we recently acquired. Last week, we announced the first preliminary results from this trial. A child who received an intraocular injection of DB-OTO in 1 year experienced improvements in hearing tests in that year through week 6 compared to baseline, including both auditory brainstem responses as well as behavioral audiometry.

最後，我想強調DB-OTO，我們的otoferlin 基因療法，這是Regeneron 的第一個針對遺傳性聽力損失的臨床項目，是我們在過去幾年中與我們最近收購的公司Decibel Therapeutics 合作開發的。上週，我們公佈了該試驗的第一個初步結果。一名在 1 年內接受眼內注射 DB-OTO 的兒童在該年至第 6 週的聽力測試中與基線相比有所改善，包括聽覺腦幹反應和行為測聽。

We are looking forward to continuing evaluation of this innovative approach in the ongoing trial for the ultra-rare otoferlin gene related hearing loss, as well as in other planned clinical programs, which include more common forms of genetic hearing loss.

我們期待在正在進行的超罕見耳鐵蛋白基因相關聽力損失試驗以及其他計劃的臨床項目（其中包括更常見形式的遺傳性聽力損失）中繼續評估這種創新方法。

In conclusion, Regeneron's R&D engine continues to grow and deliver differentiated late and early-stage opportunities, and we are looking forward to progress in the remainder of this year and looking ahead to 2024.

總而言之，再生元的研發引擎持續成長，並提供差異化的後期和早期機會，我們期待在今年剩餘時間內取得進展，並展望 2024 年。

With that, I will turn it over to Marion.

這樣，我就把它交給瑪莉安。

Thank you, George. I'm delighted to share details of our commercial performance in the third quarter, including very encouraging early signals for EYLEA HD as well as ongoing results from our in-line brands.

謝謝你，喬治。我很高興分享我們第三季度商業業績的詳細信息，包括 EYLEA HD 非常令人鼓舞的早期信號以及我們的一線品牌的持續業績。

Starting with our anti-VEGF retinal franchise, Regeneron achieved $1.49 billion in total net sales for the quarter in the U.S. We were excited to rapidly launch EYLEA HD in late August following its U.S. approval. And total net sales for the quarter were $43 million. Early launch indicators have been very positive. Physician enthusiasm was extremely high prior to EYLEA HD launch. And that interest has translated into early use in a broad range of patient types across wet AMD and diabetic eye disease.

從我們的抗 VEGF 視網膜特許經營權開始，Regeneron 本季在美國的總淨銷售額達到 14.9 億美元。我們很高興能夠在美國獲得批准後於 8 月底迅速推出 EYLEA HD。該季度總淨銷售額為 4,300 萬美元。早期的發射指標非常積極。在 EYLEA HD 推出之前，醫師的熱情非常高漲。這種興趣已轉化為早期用於濕性 AMD 和糖尿病眼疾等多種患者類型。

It is noteworthy that physicians are prescribing EYLEA HD in recalcitrant switch and naive patients. We are already hearing anecdotal case reports from physicians whose recalcitrant patients are returning. Many of these patients have now been able to achieve drawing that they were unable to obtain with other products.

值得注意的是，醫生正在為頑固性轉換患者和初次接受治療的患者開出 EYLEA HD 處方。我們已經聽到醫生的軼事病例報告，他們的頑固患者正在返回。這些患者中的許多人現在已經能夠實現使用其他產品無法獲得的繪圖效果。

To accelerate this early launch momentum, our highly experienced team is rapidly advancing reimbursement and market access. We have confirmed paid claims from 100% of Medicare jurisdictions and many large payers have recently published coverage policies for EYLEA HD. This includes both Medicare Advantage and commercial plans. While early, the speed of EYLEA HD coverage is significantly outpacing recent competitive launches.

為了加速這早期發布勢頭，我們經驗豐富的團隊正在迅速推動報銷和市場准入。我們已確認 100% 的 Medicare 司法管轄區已支付索賠，許多大型付款人最近發布了 EYLEA HD 的承保政策。這包括 Medicare Advantage 和商業計劃。雖然還處於早期階段，但 EYLEA HD 的覆蓋速度已明顯超過最近推出的競爭產品。

In addition, we continue to be on track to have a permanent J-Code by April 1, 2024, which we anticipate will drive additional uptake.

此外，我們繼續預計在 2024 年 4 月 1 日之前擁有永久的 J 代碼，我們預計這將推動更多的採用。

These early reimbursement successes and positive physician experiences are being shared by prescribers with our team and more broadly with the retina community. These initial results bode well for the future of EYLEA HD, and substantiate our belief that EYLEA HD will rapidly become the new standard of care across its approved indications. EYLEA HD's unsurpassed safety and durability demonstrated in clinical trials, coupled with prescriber confidence in EYLEA's efficacy and safety record, is expected to drive continued category leadership.

這些早期報銷的成功和積極的醫生經驗正在由處方者與我們的團隊以及更廣泛的視網膜社區分享。這些初步結果對 EYLEA HD 的未來來說是個好兆頭，並證實了我們的信念，即 EYLEA HD 將迅速成為其批准適應症的新護理標準。臨床試驗中證明 EYLEA HD 無與倫比的安全性和耐用性，加上處方者對 EYLEA 功效和安全記錄的信心，預計將繼續推動該類別的領導地位。

In summary, while the launch is still in early days, we are pleased with our progress and look forward to providing future updates. EYLEA remains the category leader with 45% anti-VEGF share for the quarter in an increasingly competitive market. With over 70 million injections worldwide since launch, EYLEA continues to demonstrate a strong and consistent safety profile, a key differentiator given retinal vasculitis and intraocular inflammation events with certain new products introduced in the retinal category. With both EYLEA HD and EYLEA, our formidable retina franchise is poured for sustained leadership.

總而言之，雖然發布仍處於早期階段，但我們對我們的進展感到滿意，並期待提供未來的更新。在競爭日益激烈的市場中，EYLEA 本季以 45% 的抗 VEGF 份額保持類別領先地位。自推出以來，EYLEA 在全球範圍內進行了超過7000 萬次注射，繼續展示強大且一致的安全性，這是視網膜類別中推出的某些新產品在視網膜血管炎和眼內炎症事件方面的一個關鍵區別因素。憑藉 EYLEA HD 和 EYLEA，我們強大的視網膜系列產品將持續保持領先地位。

Next, to Dupixent. Global net sales grew 33% year-over-year to $3.1 billion, and U.S. net sales grew 30% to $2.4 billion. This impressive third quarter performance demonstrates Dupixent's clinical and safety differentiation across all approved indications as well as its continued growth potential.

接下來，前往杜比森特。全球淨銷售額年增 33%，達到 31 億美元，美國淨銷售額成長 30%，達到 24 億美元。這一令人印象深刻的第三季業績證明了 Dupixent 在所有核准的適應症中的臨床和安全差異性及其持續成長潛力。

In the third quarter, more than 50,000 new patients are taking Dupixent in the U.S. alone, and there are now more than 750,000 patients on Dupixent worldwide. In atopic dermatitis, Dupixent's largest indication, we continue to see more than 20% growth 6 years post launch. Physicians have great confidence from the combination of efficacy, safety and ease of use across all age groups, including as young as 6 months.

第三季度，光在美國就有超過 5 萬名新患者服用 Dupixent，目前全球有超過 75 萬名患者在使用 Dupixent。在異位性皮膚炎（Dupixent 最大的適應症）方面，我們在推出 6 年後繼續看到超過 20% 的成長。醫生對所有年齡層（包括 6 個月大的嬰兒）的有效性、安全性和易用性都充滿信心。

Not only is the remarkable adherence once patients begin therapy, we also see Dupixent as being the clear treatment of choice for new patients with moderate to severe disease, with significant growth opportunity.

不僅患者開始治療後具有顯著的依從性，我們也認為 Dupixent 是中度至重度疾病新患者的明確治療選擇，具有顯著的成長機會。

In asthma, Dupixent is differentiated from all other medicines in the category based on its rapid and sustained effect on lung function, reduced exacerbations and reduced corticosteroid use. In the U.S. Dupixent continues to lead new patient prescriptions, and we are quickly approaching our goal of being the #1 prescribed medicine for asthma.

在氣喘方面，Dupixent 與該類別中所有其他藥物的不同之處在於它對肺功能的快速和持續的影響，減少了病情惡化並減少了皮質類固醇的使用。在美國，Dupixent 繼續引領新的患者處方，我們正在迅速實現成為排名第一的氣喘處方藥的目標。

Together with our partner, Sanofi, Regeneron continues to advance recent launches in eosinophilic esophagitis and prurigo nodularis, which are already meaningfully contributing to Dupixent's growth. Since FDA approval, approximately 20,000 new patients with eosinophilic esophagitis have been initiated and demand is also robust for prurigo nodularis where Dupixent is rapidly becoming the standard of care within a year of approval. We also look forward to offering Dupixent to even more patients in the future with anticipated regulatory approvals of pediatric eosinophilic esophagitis as well as multiple near-term Phase III data readouts on COPD, chronic spontaneous urticaria and bullous pemphigoid.

Regeneron 與我們的合作夥伴賽諾菲 (Sanofi) 一起繼續推進最近在嗜酸性食道炎和結節性癢疹方面的上市，這些藥物已經對 Dupixent 的增長做出了有意義的貢獻。自 FDA 批准以來，已有約 20,000 名新的嗜酸粒細胞性食道炎患者開始接受治療，對結節性癢疹的需求也很強勁，Dupixent 在批准後一年內迅速成為護理標準。我們也期待未來向更多患者提供Dupixent，預計兒童嗜酸粒細胞性食道炎將獲得監管部門的批准，以及慢性阻塞性肺病、慢性自發性蕁麻疹和大皰性類天皰瘡的多個近期III 期數據讀出。

In summary, Dupixent continues to be a key driver of our growth, and we look forward to seeing its transformational benefits extending to even more patients with type 2 inflammatory diseases across indications, demographics and geographies.

總之，Dupixent 仍然是我們成長的關鍵驅動力，我們期待看到其變革性益處擴展到更多適應症、人口統計和地理的 2 型發炎性疾病患者。

And finally, to Libtayo. Third quarter global net sales grew 59% year-over-year on a constant currency basis to $232 million, with U.S. net sales up 52% to $144 million. Global growth was driven by our non-melanoma skin indications coupled with increased utilization in both monotherapy and chemotherapy combination settings in lung cancer. We're working to expand access and use in many additional countries following recent regulatory approvals. We continue to see a growing number of prescribers choosing Libtayo when treating their patients.

最後，到 Libtayo。第三季全球淨銷售額以固定匯率計算年增 59% 至 2.32 億美元，其中美國淨銷售額成長 52% 至 1.44 億美元。全球成長是由我們的非黑色素瘤皮膚適應症以及肺癌單一療法和化療聯合治療的利用率增加所推動的。在最近獲得監管部門批准後，我們正在努力擴大在許多其他國家/地區的訪問和使用範圍。我們繼續看到越來越多的處方醫生在治療患者時選擇 Libtayo。

In conclusion, Regeneron's performance in the third quarter continues to deliver growth and value for patients and shareholders with opportunity for sustained growth. We're encouraged by favorable early indicators from the EYLEA HD launch and continue to deliver compelling performance from our in-line brands, including EYLEA, Dupixent and Libtayo.

總之，再生元第三季的業績持續為患者和股東帶來成長和價值，並有持續成長的機會。我們對 EYLEA HD 發布的良好早期指標感到鼓舞，並繼續從我們的一線品牌（包括 EYLEA、Dupixent 和 Libtayo）提供引人注目的性能。

Now I'll turn the call over to Bob.

現在我將把電話轉給鮑伯。

Thanks, Marion. My comments today on Regeneron's financial results and outlook will be on a non-GAAP basis, unless otherwise noted.

謝謝，馬里昂。除非另有說明，我今天對再生元的財務表現和前景的評論將基於非公認會計原則。

Regeneron performed well in the third quarter, with execution across the business continuing to drive strong top and bottom line growth. Third quarter 2023 total revenues increased 15% year-over-year to $3.4 billion, primarily driven by sales growth for Dupixent, coupled with improving margins within the Sanofi collaboration as well as continued growth from Libtayo.

再生元第三季表現良好，整個業務的執行力持續推動營收和利潤的強勁成長。 2023 年第三季總營收年增 15%，達到 34 億美元，主要受到 Dupixent 銷售成長、賽諾菲合作利潤率提高以及 Libtayo 持續成長的推動。

Third quarter diluted net income per share grew 4% to $11.59 on net income of $1.3 billion. This included a $100 million acquired IPR&D charge incurred in the third quarter of 2023, which decreased growth by approximately 7 percentage points.

第三季稀釋後每股淨利成長 4%，達到 11.59 美元，淨利為 13 億美元。其中包括 2023 年第三季產生的 1 億美元的智慧財產權和研發費用，這導致成長率下降了約 7 個百分點。

Moving to collaboration revenue and starting with Bayer. Third quarter 2023 ex-U.S. EYLEA net product sales were $872 million, up 6% on a constant currency basis versus the prior year. Total Bayer collaboration revenue was $377 million, of which $350 million related to our share of EYLEA net profits outside the U.S. Total Sanofi collaboration revenue was $1.1 billion in the third quarter, up 50% versus the prior year, which included the final $50 million sales-based milestone.

轉向合作收入並從拜耳開始。 2023 年第三季（美國除外） EYLEA 產品淨銷售額為 8.72 億美元，以固定匯率計算比上年增長 6%。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 淨利潤中所佔份額有關。第三季度賽諾菲合作總收入為11 億美元，比上年增長50%，其中包括最終5000 萬美元的銷售額基於里程碑。

Our share of profits from the commercialization of Dupixent and Kevzara was $863 million, an increase of 57% versus the third quarter of 2022, driven by Dupixent's continued volume growth and improving margins. As we guided last quarter, third quarter reimbursements for the manufacturing of commercial supplies from Sanofi, a component of Sanofi collaboration revenues, declined sequentially, primarily due to the ongoing phase-in of a new higher-yielding manufacturing process. In the fourth quarter, we expect a continuation of this trend with reimbursements from manufacturing of commercial supplies expected to be sequentially lower by approximately $40 million.

在 Dupixent 銷售持續成長和利潤率提高的推動下，我們從 Dupixent 和 Kevzara 商業化中獲得的利潤份額為 8.63 億美元，較 2022 年第三季增長 57%。正如我們上季度指導的那樣，第三季度賽諾菲商業用品製造的報銷（賽諾菲合作收入的一部分）連續下降，這主要是由於新的高收益製造工藝的持續逐步實施。在第四季度，我們預計這一趨勢將持續下去，商業用品製造的補償預計將環比減少約 4,000 萬美元。

Other revenues were $138 million in the third quarter of 2023, up 62% versus the prior year and inclusive of $34 million of reimbursements from BARDA for ongoing development of our next-gen COVID antibody as per the agreement announced in August 2023.

2023 年第三季的其他收入為1.38 億美元，比上一年增長62%，其中包括BARDA 根據2023 年8 月宣布的協議，為持續開發我們的下一代新冠抗體而提供的3400 萬美元的報銷。

Moving now to our operating expenses. Third quarter 2023 R&D expense grew 17% year-over-year to $954 million, representing continued investment in our expanding pipeline. R&D growth was primarily driven by higher head count and related costs in funding our advancing late-stage pipeline, as well as increased clinical manufacturing activity.

現在轉向我們的營運費用。 2023 年第三季研發費用年增 17% 至 9.54 億美元，這表明我們對不斷擴大的產品線進行了持續投資。研發成長主要是由於人員數量的增加和為推進後期管道提供資金的相關成本以及臨床製造活動的增加所推動的。

SG&A grew 14% from the prior year to $534 million in the third quarter, reflecting higher head count in related costs and higher contributions to an independent not-for-profit patient assistance organization.

第三季SG&A 較前一年成長14%，達到5.34 億美元，反映出相關成本的人員數量增加以及對獨立非營利病患援助組織的捐款增加。

In the third quarter, we recorded acquired IPR&D of $100 million, reflecting the payment of a development milestone to our collaborator, Alnylam, related to the Phase I ALN-APP program in early onset Alzheimer's disease. This impacted both GAAP and non-GAAP EPS by approximately $0.77.

第三季度，我們獲得了 1 億美元的智慧財產權和研發費用，反映了向我們的合作夥伴 Alnylam 支付的與早發性阿茲海默症 I 期 ALN-APP 計畫相關的開發里程碑付款。這對 GAAP 和非 GAAP 每股盈餘產生了約 0.77 美元的影響。

Third quarter COCM was $212 million, up 20% versus the prior year, driven by manufacturing costs associated with higher sales volumes from collaboration products, partially offset by lower Dupixent manufacturing costs. Fourth quarter COCM is expected to be the lowest quarter of the year as we continue to transition to the higher-yielding manufacturing process for Dupixent.

第三季 COCM 為 2.12 億美元，比上年增長 20%，這是由於協作產品銷售增加帶來的製造成本推動的，但 Dupixent 製造成本的降低部分抵消了這一影響。隨著我們繼續向 Dupixent 更高產量的製造流程過渡，第四季度 COCM 預計將是今年最低的季度。

Now to cash flow and the balance sheet. Through the third quarter of 2023, Regeneron generated approximately $3 billion in free cash flow and ended the third quarter with cash and marketable securities less debt of approximately $13 billion. We continue to deliver on our capital allocation priorities, buying back $507 million and $1.9 billion of our shares in the third quarter and the first 9 months of 2023, respectively, with $1.8 billion remaining authorized under our existing share repurchase program.

現在來看看現金流量和資產負債表。截至 2023 年第三季度，再生元產生了約 30 億美元的自由現金流，第三季末現金和有價證券減去債務約 130 億美元。我們繼續履行我們的資本配置優先事項，在 2023 年第三季和前 9 個月分別回購 5.07 億美元和 19 億美元的股票，其中根據我們現有的股票回購計劃仍授權 18 億美元。

Additionally, in the third quarter, we also announced and completed the acquisition of Decibel Therapeutics for approximately $100 million, to strengthen our genetics medicine portfolio. As Len mentioned, we continue to evaluate opportunities to utilize our strong financial position and build upon our core competencies with the goal of delivering long-term shareholder value.

此外，在第三季度，我們還宣布並完成了以約 1 億美元收購 Decibel Therapeutics，以加強我們的遺傳藥物組合。正如萊恩所提到的，我們將繼續評估利用我們強大的財務狀況的機會，並建立我們的核心競爭力，以實現長期股東價值。

Finally, we've made some minor changes to our full year 2023 financial guidance based on our year-to-date results and our latest outlook, updating the guidance ranges for SG&A, R&D, gross margins, COCM and capital expenditures. A complete summary of our latest full year 2023 guidance is available in our press release issued earlier this morning.

最後，我們根據年初至今的業績和最新展望對 2023 年全年財務指引進行了一些細微調整，更新了 SG&A、研發、毛利率、COCM 和資本支出的指引範圍。今天早上早些時候發布的新聞稿中提供了我們最新的 2023 年全年指導的完整摘要。

As we approach the end of 2023, I'd like to provide some commentary on the preliminary outlook for 2024. We expect continued improvements in profitability from the Sanofi collaboration, which will continue to accelerate the paydown of the antibody development balance, which as of September 30, 2023, was approximately $2.5 billion. Once this balance is fully repaid in the next few years, we expect a meaningful step-up in our share of Sanofi collaboration profits.

隨著 2023 年底的臨近，我想對 2024 年的初步展望提供一些評論。我們預計與賽諾菲的合作將持續改善盈利能力，這將繼續加速抗體開發平衡的回報，截至截至2023 年9 月30日，金額約25 億美元。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。

Separately, for Praluent, we expect significant category and competitive pressures that negatively impact U.S. sales in 2024.

另外，對於 Praluent，我們預期重大的類別和競爭壓力將對 2024 年美國銷售產生負面影響。

Moving to our operating expenses. Consistent with our capital allocation priorities, we continue to invest in our growing internal R&D pipeline to drive long-term growth. As you just heard from George, our pipeline continues to broaden, while our infrastructure to support that growth continues to expand. R&D investment in 2024 will be driven by advancing strategically important late-stage programs such as our fianlimab and Libtayo combination, confirmatory hem onc studies, including in earlier lines of therapy, our expanding collaboration in genetic medicines, as well as higher clinical manufacturing costs and the continued expansion of our R&D organization.

轉向我們的營運費用。根據我們的資本配置優先事項，我們繼續投資於不斷成長的內部研發管道，以推動長期成長。正如您剛從喬治那裡聽到的那樣，我們的產品線不斷擴大，而支持這種增長的基礎設施也在擴大。 2024 年的研發投資將受到推進具有戰略意義的後期計畫的推動，例如我們的fianlimab 和Libtayo 組合、驗證性hem onc 研究（包括早期治療系列）、我們在基因藥物方面不斷擴大的合作，以及更高的臨床製造成本和我們的研發組織不斷擴大。

With this in mind, we expect year-on-year R&D growth in 2024 to be in the mid-teens compared to our anticipated 2023 spend. We also expect to make additional investments in our commercial business and G&A functions to support the launch of EYLEA HD, our planned hem onc launches and our international expansion.

考慮到這一點，與我們預期的 2023 年支出相比，我們預計 2024 年的研發年增將達到十幾歲左右。我們還希望對我們的商業業務和 G&A 職能進行額外投資，以支持 EYLEA HD 的推出、我們計劃的 hem onc 發布以及我們的國際擴張。

In conclusion, Regeneron continues to deliver strong results, and our robust financial position allows us to make strategic investments to drive this growth over time. With that, I will now pass the call back to Ryan.

總之，再生元持續取得強勁的業績，我們穩健的財務狀況使我們能夠進行策略性投資，以推動這一成長。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 that 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 please go to the first question?

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

(Operator Instructions) Our first question comes from the line of Evan Seigerman with BMO Capital Markets.

（操作員說明）我們的第一個問題來自 BMO 資本市場的 Evan Seigerman。

Congrats on all the progress. So you have over $15 billion of cash and marketable securities on your balance sheet. Maybe Bob, you could talk about how you think about capital allocation. I know interest rates are high. But how well could you spend that money to drive even higher returns for Regeneron shareholders?

祝賀所有的進展。因此，您的資產負債表上有超過 150 億美元的現金和有價證券。也許鮑勃，你可以談談你如何看待資本配置。我知道利率很高。但你能用這筆錢為再生元股東帶來更高的回報嗎？

Yes. Thanks, Evan. I mean, I know having dealt with you and certainly many of our investors, this is certainly an issue that we've been tasked to solve. Now obviously, interest rates are a lot higher. So obviously, what we're returning on that is certainly much better than the kind of the days of 2020 and 2021. But we kind of stick to our knitting here with regards to our capital allocations. I mean George just went through a plethora of, obviously, pipeline progress that we're making. Again, first and foremost, we're going to make sure that, that is fully funded to the extent possible on that.

是的。謝謝，埃文。我的意思是，我知道在與您以及我們的許多投資者打交道後，這肯定是我們需要解決的問題。現在顯然，利率要高得多。顯然，我們的回報肯定比 2020 年和 2021 年的情況要好得多。但在資本配置方面，我們還是堅持我們的做法。我的意思是，喬治剛剛經歷了我們正在取得的大量管道進展。再說一遍，首先也是最重要的是，我們將確保盡可能提供充足的資金。

And then with regards to acquisitions, you heard with Len's intro. I mean we continue to look at a lot of opportunities. Certainly, the market that is out there on the biotech space is not in the greatest shape as you know. So again, we think there are opportunities out there. But just because we have the means, it doesn't mean that we're going to kind of push into something that may not give us an optimal result. It may not be kind of -- we like franchises, as you've heard me say that before. So we need to make sure that it's the right fit with George and the team with regards to that. So we'll continue to do that.

關於收購，您已經聽過 Len 的介紹。我的意思是我們繼續尋找很多機會。當然，生物技術領域的市場狀況並不如您所知。所以，我們再次認為那裡有機會。但僅僅因為我們有辦法，並不代表我們會去推動一些可能不會為我們帶來最佳結果的事情。這可能不是——我們喜歡特許經營權，正如你以前聽我說過的那樣。所以我們需要確保它與喬治和球隊在這方面是合適的。所以我們將繼續這樣做。

And you've seen our share repurchases, of which we're $1.9 billion through 9-months. We've done that at a very good price with regards to how we're buying that back. We're very kind of scientific in our approach on that. We do think that stock continues to be undervalued given all the pipeline progress and the catalysts that we have. So we're going to continue to push that button going forward.

您也看到了我們的股票回購，其中 9 個月的回購金額為 19 億美元。就如何回購而言，我們已經以非常優惠的價格做到了這一點。我們的方法非常科學。我們確實認為，考慮到所有管道進展和我們擁有的催化劑，股票繼續被低估。因此，我們將繼續推動這一按鈕。

So we're going to stick to our knitting. But again, as Len kind of alluded to, we are looking at a lot of opportunities that are out there. And if the right one makes the necessary fit, then we'll move forward. And again, you kind of saw that with Checkmate and Decibel, albeit those were smaller, but again, those were nice kind of franchise fits into the business.

所以我們要堅持我們的編織。但正如 Len 所提到的，我們正在尋找很多機會。如果合適的人能夠滿足必要的需求，那麼我們就會繼續前進。再說一遍，你在《Checkmate》和《Decibel》中看到了這一點，儘管它們規模較小，但同樣，這些都是適合該業務的特許經營權。

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)。

Congrats on the progress. My question is regarding the ulcerative colitis trial you are doing with Dupixent. Could you talk a little bit about the rationale behind that? And are you enriching this trial in any way on the basis of eosinophil counts or any other marker there?

祝賀取得的進展。我的問題是關於您正在使用 Dupixent 進行的潰瘍性結腸炎試驗。您能談談這背後的理由嗎？您是否根據嗜酸性粒細胞計數或任何其他標記物以任何方式豐富了這項試驗？

Yes. So as you sort of hinted at, what we have realized is that all of the diseases that we are treating with Dupixent really are interrelated diseases that reflect a systemic disorder, that is upregulation of so-called type 2 inflammation, and in some cases it manifests in the lungs, in some cases in the skin, in some cases in the gut, and so forth all over the body. And in many cases, in most patients actually in more than one location.

是的。因此，正如您所暗示的那樣，我們已經意識到，我們用 Dupixent 治療的所有疾病實際上都是相互關聯的疾病，反映了系統性疾病，即所謂的 2 型發炎的上調，在某些情況下表現在肺部，有時表現在皮膚，有時表現在腸道，等等全身各處。在許多情況下，大多數患者實際上在不只一個地點。

And so in every disease that we're going after, including now, as you mentioned, in ulcerative colitis, we believe that there are a subset of patients who may be marked with type 2 inflammation in their gut. We are, as you say, indicating -- utilizing biomarkers that might select out these patients. And so we're going to see whether a subset of ulcerative colitis patients are driven by this type 2 inflammation that's driving all the other related manifestations of this systemic disorder.

因此，在我們正在研究的每種疾病中，包括現在，正如您所提到的潰瘍性結腸炎，我們相信有一部分患者的腸道可能患有 2 型發炎。正如你所說，我們正在表明——利用生物標記可能會篩選出這些患者。因此，我們將了解是否有一部分潰瘍性結腸炎患者是由這種 2 型發炎引起的，而這種發炎會導致這種全身性疾病的所有其他相關表現。

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。

Yes. Just maybe on into COPD. I think the last time we talked to you guys on this, you were talking about the risk reward on taking an interim look on NOTUS, just given the alpha hit. It looks like you've decided to take that step here. But can you give us a sense of the alpha hit you are taking by doing this interim look?

是的。也許只是慢性阻塞性肺病。我想上次我們和你們討論這個問題時，你們談論的是考慮到 alpha 的影響，對 NOTUS 進行臨時研究的風險回報。看起來您已經決定在這裡踏出這一步。但你能否讓我們了解一下你透過這次臨時造型所受到的阿爾法打擊？

And I mean just looking at BOREAS with the 30% reduction in exacerbations, it would seem you have a decent amount of room here if NOTUS is tracking similarly. But if you can give us any more color on how you're thinking about this, the risk reward of this decision. And I assume you've got a press release that -- result of that if it's going to be the end of the year?

我的意思是，只要看看 BOREAS，惡化率減少了 30%，如果 NOTUS 也進行類似的跟踪，那麼您似乎還有相當大的空間。但如果你能給我們更多關於你如何看待這個問題的信息，以及這個決定的風險回報。我想你們已經收到一份新聞稿──如果是在今年年底，結果會如何？

Yes. We're not going to get into the details of the statistical niceties on how you do this. An alpha sparing approach is what's typical for an interim analysis. We'll work closely with Sanofi on how to do this in the most efficient manner possible and get to the information as appropriate when it appears.

是的。我們不會詳細介紹如何執行此操作的統計細節。阿爾法保留方法是中期分析的典型方法。我們將與賽諾菲密切合作，研究如何以最有效的方式做到這一點，並在資訊出現時及時獲取資訊。

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

我們的下一個問題來自瑞銀集團 (UBS) 的 Colin Bristow。

Congrats on the quarter. Not surprisingly, we've been getting an increasing number of questions on your obesity assets. And I was wondering if you could just talk to your strategy and level of enthusiasm here, and maybe frame out some of the time lines, you've got the GRP75, the leptin receptor antagonist. I think you shared some pretty provocative data at ADA on the myostatin blocker and the activin A blocker. Maybe you could just tell us your lever enthusiasm. Is this something that you're going to go full force and plan to have a major presence in down the road? Just some color there would be helpful.

恭喜本季。毫不奇怪，我們收到越來越多關於您的肥胖資產的問題。我想知道你是否可以在這裡談談你的策略和熱情程度，也許還可以製定一些時間表，你有 GRP75，瘦素受體拮抗劑。我認為您在 ADA 上分享了一些關於肌肉生長抑制素阻斷劑和激活素 A 阻斷劑的相當爭議性的數據。也許您可以告訴我們您對槓桿的熱情。您是否會全力以赴並計劃在未來佔據重要地位？只要有一些顏色就會有幫助。

Yes. As you said, we're very excited about, I guess, 2 of the approaches that we've been taking in obesity. One is our unique collection of targets that we've either been the first to discover, like the GPR75, genetically identified target that came from our Regeneron Genetics Center, which is a very exciting new target for obesity, as well as our new approaches such as our leptin receptor agonistic antibody.

是的。正如您所說，我想我們對我們在肥胖問題上採取的兩種方法感到非常興奮。其中一個是我們獨特的標靶集合，這些標靶是我們第一個發現的，例如來自我們再生元遺傳學中心的基因鑑定標靶GPR75，這是一個非常令人興奮的肥胖新標靶，以及我們的新方法，例如作為我們的瘦素受體激動性抗體。

But one thing we're doing is moving those programs forward and understanding exactly what their potential is in the field of obesity. But as you said, right now, the field, which is dominated by the GLP-1 agonists, also is recognizing increasing problems with this type of weight loss, meaning that about 40% of the weight loss is due to muscle loss. That means if you lose 20 pounds, 8 pounds of that approximately, on average, will be muscle. Most patients will never get that muscle back. This can, over time, especially if patients go off these drugs and regain the weight as fat, can create potentially a very large public health problem in dilemma.

但我們正在做的一件事是推動這些計畫並準確地了解它們在肥胖領域的潛力。但正如您所說，目前以 GLP-1 激動劑為主的領域也認識到這種類型的減肥問題越來越多，這意味著大約 40% 的體重減輕是由於肌肉損失。這意味著，如果您減掉 20 磅，平均而言，其中大約 8 磅將是肌肉。大多數患者永遠無法恢復肌肉。隨著時間的推移，特別是如果患者停用這些藥物並以脂肪的形式體重反彈，可能會造成一個非常大的陷入困境的公共衛生問題。

So we also have been, as you pointed out, very active in the field of muscle preservation and muscle growth agents. We've developed some of, I think, some of the most exciting candidates in the field that have the ability to do this. And we are certainly considering how to study these muscle preservation and muscle growth agents in combination with existing weight loss agents to see whether we can maintain or even grow muscle in the setting of weight loss. Hopefully, perhaps increasing the quality of the weight loss, maybe even resulting in greater weight loss. But most importantly, making sure that the patients in terms of their muscle and so forth, do a lot better. And we will be talking about our clinical trials in this area, we hope, very shortly.

正如您所指出的，我們在肌肉保存和肌肉生長劑領域也非常活躍。我認為，我們已經培養了一些該領域最令人興奮的候選人，他們有能力做到這一點。我們當然也在考慮如何將這些肌肉保存和肌肉生長劑與現有的減肥劑結合起來進行研究，看看我們是否可以在減肥的情況下維持甚至生長肌肉。希望也許能提高減肥的質量，甚至可能帶來更大的減肥效果。但最重要的是，確保患者在肌肉等方面做得更好。我們希望很快就會討論我們在這一領域的臨床試驗。

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

我們的下一個問題來自 TD Cowen 的 Tyler Van Buren。

Congrats on the tremendous quarterly results. It's great to see the early EYLEA HD sales, of course. And you mentioned that naive and switch patients are being treated. But are you seeing switches from Vabysmo specifically? And to what extent are you guys sending samples out as we think about assessing additional demand beyond sales?

祝賀取得了巨大的季度業績。當然，很高興看到 EYLEA HD 的早期銷售。您提到正在治療初治和轉換患者。但您是否特別看過 Vabysmo 的開關？當我們考慮評估銷售之外的額外需求時，你們在多大程度上發送了樣品？

Thanks, Tyler. So let me address the first part. And the positive anecdotal case reports we're getting back really carry across the theme of better vision, better drawing than they've seen with other anti-VEGF products. They also comment on very frequently the tremendous confidence that they have in the safety of EYLEA and the experience over many, many years.

謝謝，泰勒。那麼讓我談談第一部分。我們收到的正面的軼事案例報告確實體現了比其他抗 VEGF 產品更好的視力、更好的繪畫的主題。他們也經常評論說，他們對 EYLEA 的安全性以及多年來的經驗充滿信心。

In terms of the switches, it's early days. We are seeing switches from EYLEA, as you would expect, and of course, we're the category leaders, so there are more potential patients to consider as well. But we are also hearing switches from faricimab, we're hearing also switches from Avastin and other products in the category. And the early reports have been quite encouraging.

就開關而言，現在還處於早期階段。正如您所期望的那樣，我們看到 EYLEA 的轉變，當然，我們是該類別的領導者，因此有更多潛在患者需要考慮。但我們也聽到 Faricimab 的轉變，我們也聽到 Avastin 和該類別中其他產品的轉變。早期的報告非常令人鼓舞。

To your other part of your question related to sampling, we do have a sampling program for EYLEA HD. It's intended to give physicians experience with EYLEA HD in an appropriate way. The program is constructed on an on-demand basis. We don't disclose the number of samples or things of that sort, and certainly, that's not what you were asking. But I can share with you that we have seen a high conversion rate from practices ordering EYLEA HD samples and then subsequently placing orders of commercial products through commercial channels.

對於與抽樣相關的問題的其他部分，我們確實有 EYLEA HD 的抽樣程序。它旨在以適當的方式為醫生提供 EYLEA HD 的體驗。該程式是按需構建的。我們不會透露樣品的數量或類似的事情，當然，這不是你問的。但我可以跟大家分享的是，我們從訂購EYLEA HD樣品，然後透過商業管道訂購商業產品的做法中看到了很高的轉換率。

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

我們的下一個問題來自摩根士丹利的特倫斯·弗林。

This is Max Skor on for Terence Flynn. A quick one from us. Could you provide an update on the timing or relative implications of the biosimilar EYLEA litigation with Mylan?

我是特倫斯·弗林 (Terence Flynn) 的馬克斯·斯科爾 (Max Skor)。我們快來一張。您能否提供有關生物相似藥 EYLEA 與 Mylan 訴訟的時間安排或相關影響的最新資訊？

Yes. So we had a trial in West Virginia, a bench trial, and we are waiting for a decision from the judge. Out of our control. And as soon as it comes, it will come. It's been several months, so it could come soon or not. It's one of those things where it's really beyond our ability to predict and control.

是的。因此，我們在西維吉尼亞州進行了一次審判，一場法官審判，我們正在等待法官的決定。超出我們的控制範圍。而且既然來了，就一定會來。已經好幾個月了，可能很快就會到來，也可能不會。這是真正超出我們預測和控制能力的事情之一。

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

我們的下一個問題來自巴克萊銀行的卡特·古爾德。

Congrats on the progress. Maybe a follow-up for Marion. Thanks for all the color on the commercial dynamics for high-dose EYLEA. Can you -- one thing you didn't touch on as much though is sort of how maybe some of the step edit language has evolved? Is that sort of tracking in line with what you were seeing with standard dose EYLEA, or any broader commentary on how that's tracking relative to your expectations?

祝賀取得的進展。也許是馬里昂的後續行動。感謝您對高劑量 EYLEA 商業動態的所有關注。你能——儘管你沒有太多涉及的一件事是某些步驟編輯語言是如何演變的嗎？這種追蹤是否符合您在標準劑量 EYLEA 中看到的情況，或者是否有任何關於追蹤相對於您的期望的更廣泛的評論？

Sure. So as a quick reminder, as we get into payer mix. I'll remind everybody that these are approximate based on typical patterns in the category. It's a little bit different when you look at a product that just launched. But about 45% of our overall business is in Medicare fee-for-service. And as I mentioned to you in the call today, we've made great progress there, not only in coverage, which is the first step to get coverage but then taking the extra step to make sure that claims are being paid.

當然。快速提醒一下，當我們進入付款人​​組合時。我會提醒大家，這些是基於該類別中的典型模式的近似值。當你看一個剛推出的產品時，情況有點不同。但我們整體業務的約 45% 是按服務收費的 Medicare。正如我今天在電話中向大家提到的，我們在這方面取得了巨大進展，不僅在承保方面，這是獲得承保的第一步，而且還採取了額外的步驟來確保索賠得到支付。

So we're seeing now that 100% of Medicare fee-for-service jurisdictions have coverage and demonstrated paid claims. When we go over to Medicare Advantage, which is roughly about 25% of anti-VEGF category business and commercial, which is about 20%, what we're seeing so far, and we are making good progress with payers. We're seeing that EYLEA HD is being positioned consistently with EYLEA and other brands in the category. And there are plans, as you know, that have a step edit or utilization management. The good news is that EYLEA HD is being positioned consistently with EYLEA and other brands. We don't see a differentiation there.

因此，我們現在看到 100% 的 Medicare 按服務收費司法管轄區都有承保範圍並證明已支付索賠。當我們談到醫療保險優勢時，它大約佔抗VEGF 類別業務和商業的25% 左右，大約佔20%，這是我們迄今為止所看到的，我們在付款人方面取得了良好的進展。我們看到 EYLEA HD 的定位與 EYLEA 和該類別的其他品牌一致。如您所知，有些計劃具有步驟編輯或使用率管理。好消息是 EYLEA HD 的定位與 EYLEA 和其他品牌一致。我們沒有看到那裡有什麼區別。

Our next question comes from the line of Robyn Karnauskas with Truist Securities.

我們的下一個問題來自 Truist Securities 的 Robyn Karnauskas。

Question on CSU. I know it's a big opportunity. Many patients are not controlled well with antihistamines and you have a CRL. Is Study C sufficient? Anything in particular you think the FDA is looking for? Is there a disconnect? Are they changing how they -- what they view for the bar for approval? What's your thoughts there?

關於科羅拉多州立大學的問題。我知道這是一個很大的機會。許多患者使用抗組織胺後病情控制不佳，而您有 CRL。研究C夠嗎？您認為 FDA 正在尋找什麼特別的東西？有斷線嗎？他們是否正在改變他們對酒吧批准的看法？你有什麼想法？

Yes. Well, as you know, we had one very positive study. We had a second study, that actually had a P of 0.049, but for various statistical purposes just missed meeting its predetermined statistical hurdle, but it's certainly all the indicators are going in the right direction. And what the FDA indicated that they wanted to see the results of our ongoing Study C, as we call it, to make their decision.

是的。嗯，如你所知，我們進行了一項非常積極的研究。我們進行了第二項研究，實際上 P 值為 0.049，但出於各種統計目的，只是未能達到預定的統計障礙，但可以肯定的是，所有指標都在朝著正確的方向發展。 FDA 表示，他們希望看到我們正在進行的研究 C（我們稱之為研究 C）的結果，以便做出決定。

And so what we're hoping is that study, which is in the same population of the very positive initial study, remember, the second study was in these recalcitrant patients who have failed Xolair among other therapies. But Study C is in the same population as our very first Study A, the very positive study. And we're hoping that if we get consistent data in that study, that the FDA will consider and look favorably upon it.

所以我們希望這項研究是在非常積極的初始研究的同一人群中進行的，請記住，第二項研究是在這些頑固的患者中進行的，這些患者在 Xolair 等其他療法中都失敗了。但研究 C 與我們的第一項研究 A（一項非常積極的研究）屬於同一群體。我們希望，如果我們在該研究中獲得一致的數據，FDA 將會考慮並給予正面的對待。

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。

With regard to your cancer portfolio, as we look to additional data coming out at ASH and the proof-of-concept we've seen so far, but combination data that we're looking to with Libtayo, can you just talk to us about the optimization still required here and how you're thinking about positioning it in the context of emerging targets and competitive dynamics?

關於您的癌症組合，我們正在尋找 ASH 上發布的更多數據以及我們迄今為止看到的概念驗證，但我們正在尋找 Libtayo 的組合數據，您能和我們談談嗎這裡仍然需要優化，您如何考慮在新興目標和競爭動態的背景下對其進行定位？

Yes. We have a very large collection of combination opportunities that we're very excited about. The first one that we hope has a chance of really crossing the finish line in a very significant way, in a very seen population, is our combination of Libtayo in combination with fianlimab, putting together these 2 checkpoints, the anti-PD-1 on the anti-LAG-3.

是的。我們擁有大量的組合機會，對此我們感到非常興奮。我們希望第一個有機會在非常顯著的人群中以非常重要的方式真正跨越終點線，是我們的 Libtayo 與 fianlimab 的組合，將這 2 個檢查點放在一起，抗 PD-1抗-LAG -3。

And I think in this case, we believe we have evidence that we have the best-in-class type of activity with both agents separately. And as you've hopefully seen in our earlier stage clinical trials, the data suggests that when we put them together, we really can make a remarkable advance for patients in terms of the number of patients who respond and the extent of their progression-free survival.

我認為在這種情況下，我們相信我們有證據表明我們分別與這兩種藥物進行了同類最佳的活動。正如您希望在我們的早期臨床試驗中看到的那樣，數據表明，當我們將它們放在一起時，我們確實可以在有反應的患者數量和無進展程度方面為患者取得顯著的進步生存。

And we're now, as we announced in a pivotal trial where we hope that we will in the -- within the next year, perhaps be able to provide the results from that trial, which might confirm this remarkable advance for patients. If it works in this first-line melanoma setting, it really opens up the door to a whole series of other opportunities, both in related melanoma settings, such as an even earlier stage melanoma setting such as the adjuvant and perioperative settings, but we could be moving to other cancers as well with that proof-of-principle.

正如我們在一項關鍵試驗中所宣布的那樣，我們現在希望我們能夠在明年之內提供該試驗的結果，這可能會為患者證實這一顯著的進展。如果它在一線黑色素瘤環境中發揮作用，那麼它確實為一系列其他機會打開了大門，無論是在相關黑色素瘤環境中，例如更早期的黑色素瘤環境，例如輔助和圍手術期環境，但我們可以透過這項原理驗證，我們還將轉向其他癌症。

So that's the nearest term Libtayo checkpoint combination approach. As you know, with our bispecifics, the combination opportunities there are also very exciting, either with Libtayo or with each other. And we have, in that space, shown that our individual agents, the important thing is we have now validated so many of our individual agents as having once again the potential for best-in-class type of activity. Whether it's our agent for myeloma or our CD20 bispecific in, for example, follicular lymphoma and so forth and so on.

這就是最接近的術語 Libtayo 檢查點組合方法。如您所知，透過我們的雙特異性抗體，無論是與 Libtayo 還是彼此之間的組合機會也非常令人興奮。在這個領域，我們已經證明了我們的個體代理，重要的是我們現在已經驗證了我們的許多個體代理再次具有同類最佳活動類型的潛力。無論是我們治療骨髓瘤的藥物或是我們治療濾泡性淋巴瘤等疾病的 CD20 雙特異性藥物。

But we're also excited about our costim bispecifics. We've released the data about the incredible efficacy in at early stages that we see in combination with Libtayo. But that one, that one is countered by concerns with immune-mediated adverse events that we're seeing in these patients. It is hard to dramatically increase the extent of immunotherapy benefit without having it associated with increased autoimmune type reactions. We're working very hard on that, and we think, based on preclinical data, that the trick may be combining our costims with our CD3 bispecifics where we don't see these dramatic potential increases in the mechanisms that may lead to immune adverse events.

但我們也對我們的 costim 雙特異性抗體感到興奮。我們已經發布了與 Libtayo 結合使用的早期階段令人難以置信的功效的數據。但我們在這些患者身上看到的免疫介導的不良事件卻抵消了這一點。如果不與自體免疫型反應增加有關，就很難顯著提高免疫療法的益處。我們正在為此努力工作，我們認為，根據臨床前數據，訣竅可能是將我們的costim 與我們的CD3 雙特異性抗體結合起來，在這種情況下，我們沒有看到可能導致免疫不良事件的機制的這些巨大的潛在增加。

So in summary, our checkpoint combinations are very near term. Our bispecifics are single agents have been validated and hopefully will be being considered by the FDA for approval in the relatively near future. And the combinations are beginning to demonstrate exciting opportunity, and we're trying to tune that in order to try to present the best efficacy safety profile for patients.

總而言之，我們的檢查點組合是非常近期的。我們的雙特異性藥物是單一藥物，經過驗證，希望在不久的將來 FDA 會考慮批准。這些組合開始展現出令人興奮的機會，我們正在努力調整它，以便為患者提供最佳的療效和安全性。

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門的布萊恩亞伯拉罕斯 (Brian Abrahams)。

Congrats on the good launch so far. You mentioned in the press release some impact of price on EYLEA. I was wondering if you could elaborate a little bit more on this, when you think this might stabilize? Any extent that this might affect high-dose EYLEA as well?

祝賀到目前為止的良好發布。您在新聞稿中提到了價格對 EYLEA 的一些影響。我想知道當您認為情況可能會穩定下來時，您是否可以對此進行更多詳細說明？這是否也會影響高劑量 EYLEA？

Sure, Brian. So I would comment that, in an increasingly competitive category, there, of course, there's been some pressure on EYLEA. I'd also reflect that in 12 years in the market, it's really modest rebating and discounting if you look at the history of the brand. And of course, that on a brand that has never taken a price increase.

當然，布萊恩。因此，我想說的是，在競爭日益激烈的類別中，EYLEA 當然面臨一些壓力。我還想，如果你看看這個品牌的歷史，在市場上的12年裡，回扣和折扣確實是微乎其微的。當然，這是一個從未漲價的品牌。

But we will continue to be very much watching uptake of EYLEA HD, taking very responsible and appropriate and thoughtful measures on pricing. And certainly, as I reported to, early days, we're making some very strong progress in the marketplace in terms of making sure that physicians gain confidence in reimbursement of EYLEA HD as they initiate patients.

但我們將繼續密切關注 EYLEA HD 的使用情況，在定價方面採取非常負責任、適當且深思熟慮的措施。當然，正如我所報告的，早期我們在市場上取得了一些非常強勁的進展，確保醫生在開始治療患者時對 EYLEA HD 的報銷充滿信心。

Our next question comes from the line of Yatin Suneja with Guggenheim.

我們的下一個問題來自 Yatin Suneja 與古根漢的關係。

Question on Dupixent. Could you maybe share your views on the newer mechanism? For example, OX-40 or perhaps a longer-acting version of Dupixent on the franchise? Maybe if you can talk about your efforts in terms of life cycle management of Dupixent?

關於 Dupixent 的問題。能否分享一下您對新機制的看法？例如，OX-40 或特許經營中 Dupixent 的長效版本？也許您可以談談您在 Dupixent 生命週期管理方面所做的努力？

Yes. Maybe getting back to some of the comments that I made before. The collection of so-called allergic or type 2 conditions, which Dupixent addresses are all characterized by a systemic inflammatory problem increase in the so-called type 2 inflammation. Which if you look at the science and literature is really of this digital pathway that largely evolved and was one of the most active parts of the immune system, to fight things like fecal parasites, which are really not an issue now in the developed world.

是的。也許回到我之前發表的一些評論。 Dupixent 所解決的所謂過敏或 2 型病症的集合，其特徵都是所謂的 2 型發炎中全身性發炎問題的增加。如果你看一下科學和文獻，這確實是這種數字途徑的一部分，它在很大程度上是進化而來的，是免疫系統最活躍的部分之一，可以對抗糞便寄生蟲等東西，而這在已開發國家現在確實不是問題。

This part of the immune system should essentially in the modern world be entirely quiescent. It serves almost no role. The problem is it becomes unleashed abnormally to do things that it shouldn't be doing, like fighting allergens or attacking the skin or the gut in atopic dermatitis or eosinophilic esophagitis.

在現代世界中，免疫系統的這一部分基本上應該是完全靜止的。它幾乎沒有任何作用。問題是它會異常釋放，去做不該做的事情，例如對抗過敏原或攻擊異位性皮膚炎或嗜酸性食道炎的皮膚或腸道。

What Dupixent does uniquely is that it controls, and the data now demonstrate this, the incredible effect, that it puts this useless angry tiger back in the cage where it belongs. And that is why it has this incredible profile of not only efficacy but safety. Because what's shutting down is it's shutting down a pathway that should be vestigial in the modern world, that becomes unleashed and attacks all different parts of the body.

Dupixent 的獨特之處在於它能夠控制，現在的數據證明了這一點，令人難以置信的效果，它將這只無用的憤怒老虎放回了它所屬的籠子裡。這就是為什麼它不僅具有令人難以置信的功效而且安全性。因為關閉的是它關閉了一條在現代世界中本應殘留的通路，這條通路被釋放並攻擊身體的所有不同部位。

We believe that any of this current competition that's ongoing doesn't share these remarkable features that give Dupixent its incredible broad efficacy across the spectrum of diseases with its unique safety profile. Because all of these other approaches, including, for example, the OX-40 approach and so forth, are addressing different fundamental immune pathways that are important in the immune system's function to do a lot of actual useful things in the modern world. Like, for example, fighting viral infections in cancer and so forth.

我們相信，目前正在進行的任何一項競爭都沒有這些顯著的特徵，而正是這些特徵使 Dupixent 在多種疾病上具有令人難以置信的廣泛功效及其獨特的安全性。因為所有這些其他方法，包括 OX-40 方法等，都在解決不同的基本免疫途徑，這些途徑對於免疫系統的功能非常重要，可以在現代世界中完成許多實際有用的事情。例如，對抗癌症中的病毒感染等。

So Dupixent really has a very unique profile, which if we can help explain and if all physicians and patients can understand it, make it the perfect drug for this condition. It uniquely blocks this digital pathway that gets out of control and appropriately and causes disease all over the body. Dupixent shuts down this what should be a vestigial pathway, and it helps disease, whether in the same patients, it could be manifesting in the skin in the lungs, in the nose, in the gut and so forth, it shuts it down without really untoward effects with regards to the ability of the body to actually fight infections and so forth.

因此，Dupixent 確實具有非常獨特的特徵，如果我們能夠幫助解釋，並且如果所有醫生和患者都能理解它，那麼它就會成為治療這種情況的完美藥物。它獨特地阻止了這種數位通路的失控並適當地導致全身性疾病。 Dupixent 關閉了這個應該是殘留的通路，它有助於疾病，無論是在同一個患者中，它可能表現在肺部、鼻子、腸道等皮膚上，它關閉它而沒有真正的作用。對身體實際抵抗感染的能力等產生不良影響。

In fact, if you look at our clinical studies and some of the data that we published, in many, if not most cases, you actually see unbelievably reduced infections in the setting of the Dupixent treatment. Because what you're doing is you're putting the bad part of the immune system back under control and you're allowing the rest of immune system to do its function.

事實上，如果您查看我們的臨床研究和我們發布的一些數據，在許多（如果不是大多數）案例中，您實際上會發現 Dupixent 治療的感染率令人難以置信地減少。因為你所做的就是讓免疫系統的不良部分重新受到控制，並讓免疫系統的其他部分發揮其功能。

All of these other approaches are trying to attack critical parts of the immune system that have important other functions, and they don't address the widespread problem that occurs systemically and causes all of these diseases. So as you've seen already with various agents, they may work in one of Dupixent indications, but they don't work, they failed in other indications. And if they work, they also often come with the concerns about safety because they're designed to be immunosuppressive, which Dupixent is not.

所有這些其他方法都試圖攻擊具有重要其他功能的免疫系統的關鍵部分，而且它們無法解決系統性發生並導致所有這些疾病的普遍問題。正如您已經看到的各種藥物，它們可能對 Dupixent 適應症之一有效，但它們不起作用，在其他適應症中失敗。即使它們有效，也常常會帶來安全性擔憂，因為它們被設計為具有免疫抑製作用，而 Dupixent 則不然。

So just to add a small point to what George's eloquent explanation of why Dupixent is such a special drug and the prediction that it would be safe because it's attacking this vestigial part of the immune system, you're looking at somewhere in the neighborhood of 0.75 million people on the drug, many more than that so that have demonstrated the safety that is predicted by the science.

因此，喬治雄辯地解釋了為什麼 Dupixent 是一種如此特殊的藥物，並預測它是安全的，因為它攻擊的是免疫系統的這個殘餘部分，為了補充一點，你會看到 0.75 附近的某個地方百萬人服用該藥物，遠不止於此，證明了科學預測的安全性。

Including in children, as we know, as young as 6 months is approved there where it's been demonstrating not only incredible safety but incredible efficacy.

據我們所知，包括兒童在內，小至 6 個月大的兒童就已獲得批准，該藥物不僅表現出令人難以置信的安全性，而且具有令人難以置信的功效。

Shannon, I think we have time for 2 more questions, please.

Shannon，我想我們還有時間再問兩個問題。

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 a strong quarter. Just actually really 2 quick ones for me. First one being, can you just comment whether you saw any impact from increased utilization of biosimilar ranibizumab during the quarter on EYLEA sales. A number of high-volume clinics had highlighted favorable margin opportunities from using more biosimilar ranibizumab which seems to be potentially a transient impact and use of some of the brands, but it would be interested in your commentary there.

恭喜季度表現強勁。對我來說實際上只有兩個快速的。首先，您能否評論一下本季生物相似藥雷珠單抗的使用增加是否對 EYLEA 銷售產生任何影響。許多大批量診所強調了使用更多生物相似藥雷珠單抗帶來的有利利潤機會，這似乎可能是某些品牌的短暫影響和使用，但它會對您的評論感興趣。

And then we've gotten just a lot of inbounds in terms of ongoing patent litigation of EYLEA. Could you just maybe state for us what your current expectation is for EYLEA patent life? And just any thoughts you have on how the ruling that we're awaiting could actually impact your base case.

然後，我們在 EYLEA 正在進行的專利訴訟中收到了大量的投訴。您能否為我們說明您目前對 EYLEA 專利壽命的期望？您對我們正在等待的裁決如何實際影響您的基本情況的任何想法。

Yes. So I'll cover the patents and then Marion can cover any additional insight into the marketplace. On the patents, we're involved in litigation. There's a couple of key patents that have evolved in this case that both relate to formulation as well as dosing. On the base case is that, for us, assuming that the exclusivity will expire in May, but we will see what happens in the litigation, which could be an upside, obviously, for the franchise.

是的。因此，我將介紹專​​利，然後馬里昂可以介紹對市場的任何其他見解。在專利方面，我們捲入了訴訟。在這種情況下，出現了一些關鍵專利，它們都與配方和劑量有關。基本情況是，對我們來說，假設排他性將於五月到期，但我們將看看訴訟中會發生什麼，這顯然對特許經營權來說可能是一個好處。

All right. And on the ranibizumab impact, it's relatively early in their launches, and -- but there hasn't been a notable impact to the category. The Lucentis biosimilar shares in the low single-digit area in the third quarter, and certainly, the impact has been seen more relative to Lucentis, which has declining share. But certainly, this is not extended to EYLEA HD.

好的。就雷珠單抗的影響而言，其上市時間相對較早，而且——但尚未對該類別產生顯著影響。第三季 Lucentis 生物相似藥的份額處於低個位數區域，當然，相對於份額不斷下降的 Lucentis 而言，其影響更大。但當然，這並沒有擴及到 EYLEA HD。

We'll just take our last question, please, Shannon.

我們只回答最後一個問題，香農。

Our last question is from the line of Brian Skorney with Baird.

我們的最後一個問題來自 Brian Skorney 和 Baird 的對話。

It looks like J&J had a really good first quarter of their myeloma bispecific. So it definitely seems like there's a good demand there. But also an element of them having control of a lot of offerings for myeloma. So obviously, head-to-head superiority would always dominate each in oncology, but with the initial launch of your bispecific next year. I'm just wondering what your strategy is for competing in the initial late line as a third-to-market? Do you think that there is differentiated enough data here to kind of take share? Or is the focus really on generating data in earlier line of combos to kind of move up market share?

看起來強生公司的骨髓瘤雙特異性藥物第一季表現非常好。所以看來那裡確實有很好的需求。但也是他們控制大量骨髓瘤產品的因素。很明顯，在腫瘤學領域，面對面的優勢將始終佔據主導地位，但隨著明年雙特異性抗體的首次推出。我只是想知道你們作為第三個進入市場的公司在最初的後期競爭中的策略是什麼？您認為這裡有足夠的差異化數據來分享嗎？或者，重點真的是在早期的組合中產生數據以提高市場份額嗎？

Well, of course, it's both. We do believe that data rules, the best, both efficacy, safety profile but also convenience profile. And we will be continuing to show our evolving and maturing data, which we believe could result in best-in-class in terms of efficacy, in terms of response rates and complete response rates in terms of safety, in terms of the frequency of cytokine release syndrome and so forth. And in terms of differentiation in terms of mandated hospitalization.

嗯，當然，兩者都是。我們確實相信資料規則是最好的，既具有功效、安全性，又具有便利性。我們將繼續展示我們不斷發展和成熟的數據，我們相信這些數據可以在功效、緩解率和完全緩解率、安全性、細胞激素頻率方面實現同類最佳釋放綜合徵等。在強制住院方面的差異化。

So we will be continuing to present our data. Of course, we'll see exactly ultimately what gets in the label and what the FDA supports but there's the potential here for best-in-class differentiation in terms of efficacy, safety and convenience and schedule. And of course, as you said, we're also moving with, we think, an exciting program in earlier lines of therapy. And all of this is also going to be combined with the opportunities for our future combinations. We have a variety of costim bispecifics that we're excited about combining specifically with this agent in the plasma cell dyscrasia setting.

因此，我們將繼續展示我們的數據。當然，我們最終會確切地看到標籤上的內容以及 FDA 支援的內容，但在功效、安全性、便利性和時間表方面有可能實現一流的差異化。當然，正如您所說，我們認為，我們也在早期治療中開展一項令人興奮的計劃。而這一切也將與我們未來的組合機會結合。我們有多種 Costim 雙特異性藥物，我們很高興能在漿細胞惡液質環境中與該藥物專門結合。

So we think it's a very exciting opportunity. As you said, unfortunately, there's a large opportunity out there because there's a lot of patients that are still in need. I think that if you have the best agent for late-stage patients. A lot of people want to use it. And then if we figure out the best program to demonstrate how it can be utilized in earlier-stage patients that can certainly enhance that opportunity let alone if we come up with one of our magic combos that really takes it to the whole next level.

所以我們認為這是一個非常令人興奮的機會。正如你所說，不幸的是，那裡有很大的機會，因為仍有許多患者需要治療。我認為如果你有針對晚期患者的最佳藥物。很多人都想使用它。然後，如果我們找到最好的程序來展示如何將其用於早期患者，這肯定可以增加這個機會，更不用說如果我們想出一個神奇的組合，真正將其提升到一個新的水平。

Okay. Thanks, George, and thanks to everyone who dialed in today and for your interest in Regeneron. We apologize to those remaining in the queue that we do not have a chance to hear from. But as always, the Investor Relations team here is available to answer any remaining questions you may have. 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的人致歉，我們沒有機會收到他們的消息。但與往常一樣，這裡的投資者關係團隊可以回答您可能遇到的任何剩餘問題。再次感謝您，祝您有美好的一天。

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

今天的電話會議到此結束。感謝您的加入。您現在可以斷開連線。