雷傑納榮製藥 (REGN) 2022 Q3 法說會逐字稿

Hello, and welcome to Regeneron Pharmaceuticals Third Quarter 2022 Earnings Conference Call. My name is Towanda; and I will be your operator for today's call. (Operator Instructions) Please note that this conference is being recorded.

您好，歡迎參加再生元製藥公司2022年第三季財報電話會議。我是Towanda，將擔任本次電話會議的接線生。 （接線生說明）請注意，本次會議正在錄音。

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

現在我將把電話交給投資者關係副總裁瑞安·克羅。您可以開始了。

Thank you, Towanda. Good morning, good afternoon and good evening to everyone listening around the globe. Thank you for your interest in Regeneron and welcome to our third quarter 2022 earnings conference call. An archive of this webcast will be available on our Investor Relations website shortly after the call ends. Joining me today are Dr. Leonard Schleifer, Founder, President and Chief Executive Officer; Dr. George Yancopoulos, 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.

謝謝Towanda。各位全球聽眾，早安、下午好、晚上好。感謝您對Regeneron的關注，歡迎參加我們2022年第三季財報電話會議。本次網路直播的存檔將在會議結束後不久發佈在我們的投資者關係網站上。今天與我一同出席會議的有：創辦人、總裁兼執行長Leonard Schleifer博士；共同創辦人、總裁兼首席科學官George Yancopoulos博士；執行副總裁兼商務主管Marion McCourt；以及執行副總裁兼財務長Bob Landry。在我們發言結束後，我們將進入問答環節。

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

我還要提醒各位，今天電話會議所作的發言包含有關Regeneron公司的前瞻性陳述。這些陳述可能包括但不限於與Regeneron及其產品和業務、財務預測和指導、研發項目及相關預期里程碑、合作、財務、監管事宜、支付方覆蓋範圍和報銷問題、知識產權、未決訴訟和其他程序以及競爭相關的陳述。

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, 2022, which was filed with the SEC this morning.

每項前瞻性聲明均受風險和不確定性因素的影響，這些因素可能導致實際結果和事件與聲明中預測的結果和事件有重大差異。有關這些風險和其他重大風險的更完整描述，請參閱Regeneron向美國證券交易委員會提交的文件，包括其截至2022年9月30日的季度報告（10-Q表格），該報告已於今天上午提交給美國證券交易委員會。

Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. In addition, please note that GAAP and non-GAAP 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, which can be accessed on our website. Once our call concludes, Bob Landry and the IR team will be available to answer further questions.

再生元公司不承擔任何更新前瞻性聲明的義務，無論是因為新資訊、未來事件或其他原因。此外，請注意，今天的電話會議將討論GAAP和非GAAP財務指標。有關我們使用非GAAP財務指標以及這些指標與GAAP的調節表的信息，請參閱我們網站上發布的財務業績新聞稿。電話會議結束後，Bob Landry和投資者關係團隊將解答您的其他問題。

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

那麼，現在讓我把電話交給我們的總裁兼執行長倫‧施萊弗博士。倫？

Thank you, Ryan, and thank you to everyone joining today's call. Regeneron's strong operational momentum continued in the third quarter, highlighted by important developments across our pipeline and outstanding commercial execution. Total revenues for the quarter increased by 11% compared to last year when excluding contributions from our COVID antibody cocktail With global net sales of Dupixent and Libtayo, as well as U.S. net sales of EYLEA once again reaching new all-time quarterly highs and growing by double digits.

謝謝瑞安，也謝謝今天所有參加電話會議的各位。再生元在第三季度繼續保持強勁的營運勢頭，這主要得益於我們研發管線的重要進展和卓越的商業執行。若不計入新冠抗體雞尾酒療法的貢獻，本季總營收較去年同期成長11%。 Dupixent和Libtayo的全球淨銷售額，以及EYLEA在美國的淨銷售額，再次創下季度歷史新高，並實現了兩位數的成長。

Before diving deeper into our commercial results, I'd like to review some of the recent progress we have made across our pipeline, starting with the striking pivotal data that we reported in September for our investigation of aflibercept 8 milligrams, which we believe could ultimately transform the treatment landscape for patients. With nearly 90% of DME patients and 80% of wet AMD patients able to sustain 16 weeks maintenance dosing through 48 weeks of treatment, we believe aflibercept 8 milligrams may shift the current treatment paradigm with more patients receiving less frequent injections while achieving visual acuity gains, anatomical improvements and a safety profile comparable to EYLEA. It has proven to be very difficult to decrease the treatment burden beyond what we were able to achieve with EYLEA over a decade ago with many potential treatments failing either due to suboptimal visual outcomes or safety issues.

在深入探討我們的商業成果之前，我想先回顧一下我們研發管線近期取得的一些進展，首先是我們在9月份公佈的關於阿柏西普8毫克劑量研究的關鍵性數據，我們相信這些數據最終可能會徹底改變患者的治療格局。近90%的糖尿病性黃斑水腫（DME）患者和80%的濕性老年性黃斑部病變（AMD）患者能夠在48週的治療期間維持16週的劑量，我們相信阿柏西普8毫克劑量有望改變目前的治療模式，使更多患者能夠接受更少的注射，同時獲得視力提升、眼部結構改善，並且安全性與眼部結構相當安全性與眼部結構相當，並且相當安全性與眼部結構改善，並且相當安全性與眼部結構改善性與眼部結構相當，並且相當安全性與眼部結構相當。事實證明，要進一步降低治療負擔非常困難，而這已經是我們十多年前使用EYLEA所取得的成就了，許多潛在的治療方案都因視覺效果不佳或安全性問題而失敗。

A recently approved anti-VEGF agent did not demonstrate in pivotal studies that the majority of patients in either the disease were able to sustain 16-week maintenance dosing throughout the first year of treatment, supporting our view that aflibercep 8 milligrams has the potential to become the next-generation standard of care anti-VEGF treatment, assuming regulatory approval. We plan to submit the aflibercep 8-milligram pivotal data to the FDA under a single BLA at the end of this year and have decided to use a previously granted priority review voucher to expedite the FDA review process. Prelaunch planning is already underway with the potential FDA approval by late August 2023.

近期獲準的一種抗VEGF藥物在關鍵性研究中未能證實大多數患者能夠在治療的第一年內持續接受16週的維持劑量，這支持了我們的觀點，即8毫克阿柏西普有望成為下一代抗VEGF治療的標準療法（假設獲得監管部門批准）。我們計劃在今年底以單一生物製品許可申請（BLA）的形式向FDA提交8毫克阿柏西普的關鍵性數據，並已決定使用先前獲得的優先審評券來加快FDA的審查流程。上市前準備工作已啟動，預計2023年8月底獲得FDA批准。

In addition to the pivotal of aflibercep 8 milligram data, Regeneron continue to make notable progress in our immunology and oncology pipelines. Starting with immunology. In September, we received FDA approval for Dupixent in prurigo nodularis, the first systemic therapy for this indication and the fifth disease for which Dupixent is now approved.

除了aflibercep 8毫克劑量資料的關鍵性進展外，Regeneron在免疫學和腫瘤學研發管線方面也持續取得顯著進展。首先是免疫學方面。今年9月，Dupixent獲得FDA核准用於治療結節性癢疹，這是第一個用於此適應症的全身性療法，也是Dupixent核准的第五種疾病。

So far this year, Dupixent has received 4 U.S or EU regulatory approvals, expanding the treatment-eligible population by approximately 225,000 patients including 2 diseases that previously had no FDA-approved systemic therapies.

今年到目前為止，Dupixent 已獲得 4 項美國或歐盟監管部門的批准，使符合治療條件的患者人數增加了約 225,000 人，其中包括 2 種以前沒有 FDA 批准的系統性療法的疾病。

In the first half of next year, we are looking forward to EU regulatory decisions for eosinophilic esophagitis, prurigo nodularis and atopic dermatitis in patients as young as 6 months. With these potential additional indications, approximately 200,000 more patients with these type 2 inflammatory diseases could benefit from Dupixent's unmatched clinical profile. Additionally, we expect pivotal data readouts for Dupixent in chronic inducible cold urticaria, and chronic obstructive pulmonary disease in the first half of next year.

明年上半年，我們期待歐盟監管機構就Dupixent用於治療嗜酸性食道炎、結節性癢疹和異位性皮膚炎（適用於6個月及以上嬰兒）做出審批決定。這些潛在的新增適應症將使約20萬名患有此類2型發炎性疾病的患者受益於Dupixent無與倫比的臨床療效。此外，我們預計明年上半年也將公佈Dupixent治療慢性誘發性寒冷性蕁麻疹和慢性阻塞性肺病的關鍵性數據。

Moving to Oncology, where the depth and breadth of our pipeline has positioned Regeneron to ultimately become a global leader. We presented several data sets at this year's European Society for Medical Oncology Annual Meeting, further underscoring the importance of Libtayo as the foundation for our overall oncology strategy. George will review the data in more detail during his remarks, but we were particularly encouraged by the results for Libtayo monotherapy in neoadjuvant CSCC as well as the Libtayo combination with Fianlimab, our LAG-3 antibody in first-line metastatic melanoma. We also presented monotherapy data for our MUC16xCD3 bispecific in recurrent ovarian cancer which has the potential will be combined with Libtayo as well as data for our METxMET biparatopic, bispecific in metaled non-small cell lung cancer. I'd also note the early but very exciting results for our PSMA by CD28 Co-stimulatory bispecific in combination with Libtayo, which showed promising antitumor activity in patients with advanced metastatic castrate-resistant prostate cancer.

進入腫瘤領域，我們豐富的產品線使Regeneron最終成為全球領導者。在今年的歐洲腫瘤內科學會年會上，我們展示了多項數據，進一步強調了Libtayo作為我們整體腫瘤策略基石的重要性。 George將在發言中更詳細地介紹這些數據，但我們尤其對Libtayo單藥治療新輔助皮膚鱗狀細胞癌（CSCC）以及Libtayo聯合Fianlimab（我們的LAG-3抗體）治療一線轉移性黑色素瘤的結果感到鼓舞。我們也展示了MUC16xCD3雙特異性抗體單藥治療復發性卵巢癌的數據，該抗體有望與Libtayo聯合使用；此外，我們還展示了METxMET雙位點雙特異性抗體治療轉移性非小細胞肺癌的數據。我還要指出，我們的 PSMA by CD28 共刺激雙特異性抗體與 Libtayo 聯合用藥的早期但非常令人興奮的結果，該抗體在晚期轉移性去勢抵抗性前列腺癌患者中顯示出有希望的抗腫瘤活性。

The patients enrolled in our study have a poor prognosis with an expected survival of 1 to 2 years, depending upon their treatment history. Given prostate cancer has been largely unresponsive to PD-1 inhibition and immunotherapy in general, there is a clear need for new treatments. In 2020 alone, there were over 375,000 deaths globally from prostate cancer and it was the second leading cause of cancer death in American Man. We continue to expand our co-stimulatory bispecific efforts in prostate cancer with an acceleration in enrollment in our first-in-human study since we reported our top line results in August, and we look forward to updating you on this program in the first half of next year.

我們研究中的患者預後較差，預期存活期為1至2年，取決於其既往治療史。鑑於前列腺癌對PD-1抑制劑和免疫療法普遍反應不佳，因此迫切需要新的治療方法。光是2020年，全球就有超過37.5萬人死於攝護腺癌，是美國男性癌症死亡的第二大原因。自8月公佈初步結果以來，我們一直在加速推進前列腺癌首項人體試驗的入組，並持續擴大雙特異性共刺激抗體在前列腺癌領域的應用。我們期待在明年上半年向您報告該專案的最新進展。

Now turning to our commercial performance. In the third quarter, EYLEA global net sales grew 8% at constant currency to $2.4 billion. In the U.S., EYLEA net sales were $1.63 billion, up 11% year-over-year and outperforming the anti-VEGF category growth of only 4%. Despite recent branded and biosimilar entrants, EYLEA set a new all-time high for anti-VEGF category share in the United States.

現在來看我們的商業業績。第三季度，安禮全球淨銷售額以固定匯率計算成長8%，達到24億美元。在美國，安禮淨銷售額為16.3億美元，較去年同期成長11%，遠超抗VEGF藥物品類4%的整體成長速度。儘管近期有品牌藥和生物相似藥進入市場，安禮在美國抗VEGF藥品品類的市佔率仍創下歷史新高。

Dupixent continued to grow at a remarkable pace bolstered by approvals in new diseases and younger patient populations in previously approved indications. In the third quarter, global net product sales were $2.3 billion, up 45% at constant currency compared to last year, reflecting growth across all indications in all geographies. And Dupixent's differentiated clinical profile and ability to effectively treat more and more patients in both currently approved indications and potentially for additional type 2 inflammatory diseases -- is expected to drive strong growth in the future.

由於新疾病的批准以及在已批准適應症中更年輕患者群體的拓展，Dupixent 繼續保持顯著的增長勢頭。第三季度，全球淨產品銷售額達 23 億美元，以固定匯率計算年增 45%，反映出所有適應症和所有地區均實現成長。 Dupixent 獨特的臨床特性及其在現有已獲準適應症以及潛在其他 2 型發炎性疾病領域有效治療更多患者的能力，預計將在未來推動強勁成長。

Libtayo total net sales grew 25% globally at constant currency to $143 million in the third quarter, including 21% growth in the United States driven by non-melanoma skin cancer indications and monotherapy non-small cell lung cancer. At the start of the third quarter, we acquired global rights to Libtayo from Sanofi with potential future combinations, including with chemotherapy in non-small cell lung cancer as well as other pipeline agents in development, we believe Libtayo is poised to become a more meaningful revenue contributor over time.

第三季度，Libtayo全球淨銷售額以固定匯率計算成長25%，達到1.43億美元，其中美國市場成長21%，主要得益於非黑色素瘤皮膚癌適應症和非小細胞肺癌單藥治療的推動。第三季初，我們從賽諾菲手中收購了Libtayo的全球權益。鑑於未來可能與其他藥物合併使用，包括與非小細胞肺癌化療藥物以及其他在研藥物，我們相信Libtayo有望隨著時間的推移成為更重要的收入貢獻者。

We are excited about the strong commercial performance for our core products, the compelling efficacy, safety and durability data that we reported for aflibercep 8 milligrams as well as the notable progress we have made advancing our pipeline, particularly in oncology. Our pipeline now includes approximately 35 product candidates in clinical development including a number of marketed products that we're investigating for additional indications, some of which George will discuss in a moment.

我們對核心產品的強勁商業表現感到振奮，尤其對8毫克阿柏西普的顯著療效、安全性和持久性數據感到滿意。此外，我們在推進產品線方面也取得了顯著進展，尤其是在腫瘤領域。目前，我們的產品線包含約35個處於臨床開發階段的候選產品，其中包括一些已上市產品，我們正在研究其在其他適應症方面的應用，喬治稍後會詳細介紹其中的一些。

In closing, our strategy continues to focus on investing in our internal R&D capabilities while exploring potential collaborations that will enable us to fully realize the power of our science. We remain confident in this strategy and in our growth prospects as well as in our ability to deliver breakthroughs to patients and value to shareholders.

最後，我們的策略仍然是專注於投資內部研發能力，同時探索潛在的合作機會，以充分發揮我們的科學實力。我們對這項策略、成長前景以及為患者帶來突破性進展和為股東創造價值的能力充滿信心。

Now I'll turn the call over to George.

現在我把電話交給喬治。

Thank you, Len. I'll start with ophthalmology. The positive pivotal results for aflibercept 8-milligram in the PULSAR and PHOTON studies, we recently presented the American Academy of Ophthalmology Annual Meeting. The results of these trials in wet AMD and DME, respectively, demonstrated that a remarkably high percentage of patients were able to be rapidly initiated into and then successfully maintained through week 48 on 12- and 16-week dosing intervals. While achieving vision gains that were not inferior to the current standard of care, EYLEA 2-milligram dose every 8 weeks. These results suggest that aflibercept 8 milligrams has the potential to become the new standard of care in these retinal diseases. I think it would be helpful if we step back for a minute and try to put these results in context.

謝謝Len。我先從眼科方面說起。我們最近在美國眼科學會年會上公佈了PULSAR和PHOTON研究中阿柏西普8毫克的積極關鍵性結果。這些試驗分別針對濕性老年黃斑部病變（AMD）和糖尿病黃斑水腫（DME）患者，結果表明，相當高比例的患者能夠快速開始接受治療，並在12週和16週的給藥間隔下成功維持治療至第48週。同時，患者的視力改善效果不遜於目前的標準治療方案－每8週一次的EYLEA 2毫克。這些結果表明，阿柏西普8毫克有望成為這些視網膜疾病的新標準治療方案。我想，如果我們先回顧一下，將這些結果放在更廣闊的背景下解讀，會很有幫助。

While what our trials did was push the limits far beyond what has been accomplished with any currently available anti-VEGF therapies. Rather than using response criteria to try to identify or slowly extend patients to longer dosing intervals, our trials tested whether all patients could be randomly assigned and rapidly initiated on extended dosing intervals of aflibercept 8-milligram without compromising visual improvement or safety. These aflibercept 8-milligram trials accomplished just that for the vast majority, while delivering a safety profile consistent with that of EYLEA. 89% of DME patients and 77% of wet AMD patients -- we're able to be rapidly initiated and maintained on a 16-week of aflibercept 8-milligram dosing regimen, while 93% of DME and 83% of wet AMD patients we're able to be rapidly initiating maintained on at least a 12-week dosing interval, all while delivering efficacy similar to that of EYLEA administered every 8 weeks.

我們的試驗突破了現有任何抗VEGF療法的極限。我們沒有採用療效評估標準來篩選或逐步延長患者的給藥間隔，而是測試了所有患者能否在不影響視力改善或安全性的前提下，隨機分組并快速啟動8毫克阿柏西普的延長給藥間隔治療。這些8毫克阿柏西普的試驗在絕大多數患者中實現了這一目標，同時安全性與EYLEA相當。 89%的糖尿病黃斑水腫（DME）患者和77%的濕性老年性黃斑部病變（AMD）患者能夠快速啟動並維持16週的8毫克阿柏西普給藥方案，而93%的DME患者和83%的濕性AMD患者能夠快速啟動並維持至少12週的給藥間隔，且療效的83%的濕性AMD患者能夠快速啟動並維持至少12週的給藥間隔，且療效的83%的水分EY

We believe these are truly unprecedented and potentially game-changing results, which have not been achieved using any other anti-VEGF agent. This has speculated that our PDUFA and PHOTON results were due to our dose modification criteria and even try to theoretically extrapolate that their agent could have somehow approached these results using our criteria. We put these speculative extrapolations into the category of wishful thinking. And based on our expert analysis of the data, we conclude it is all about the drug and not the trial design.

我們相信這些結果是前所未有的，並且可能具有顛覆性的意義，是其他任何抗VEGF藥物都無法達到的。有人推測，我們的PDUFA和PHOTON試驗結果是由於我們採用的劑量調整標準，甚至有人試圖從理論上推斷，他們的藥物如果採用我們的標準，或許也能達到類似的結果。我們認為這些推測純屬一廂情願。基於我們對數據的專家分析，我們得出結論：關鍵在於藥物本身，而非試驗設計。

Briefly moving on to Dupixent. Building on our recent approval in eosinophilic esophagitis in adults and adolescents, we are planning on submitting a supplementary BLA for eosinophilic esophagitis and in 1- to 11-year-old children in mid-2023. Dupixent ability to treat eosinophilic esophagitis highlights how important it is that our IL-4 and IL-13 blocker more completely targets the entire type 2 inflammatory cascade and not only eosinophils.

接下來簡單談談Dupixent。基於我們近期獲準用於治療成人和青少年嗜酸性粒細胞性食道炎，我們計劃於2023年中期提交Dupixent用於治療1至11歲兒童嗜酸性粒細胞性食道炎的補充生物製品許可申請（SLA）。 Dupixent治療嗜酸性粒細胞性食道炎的能力凸顯了我們的IL-4和IL-13阻斷劑能夠更全面地靶向整個2型發炎級聯反應（而不僅僅是嗜酸性粒細胞）的重要性。

As you heard Len mentioned, the FDA label was expanded yet again in the third quarter as Dupixent became the first and only treatment indicated for prurigo nodularis, a debilitating chronic skin disease. This marks the fifth disease for which Dupixent is now approved. Our collective clinical data with Dupixent support a unifying molecular mechanism underlying these related diseases from asthma to atopic dermatitis to nasal polyps to prurigo nodularis to eosinophilic esophagitis. In this unifying hypothesis, IL-4 and IL-13 induced inflammation is driving all of these related diseases in different tissue compartments.

正如Len所提到的，FDA在第三季度再次擴大了Dupixent的適應症範圍，使其成為首個也是目前唯一獲批用於治療結節性癢疹（一種嚴重的慢性皮膚病）的藥物。這標誌著Dupixent核准的適應症已增加到第五種。我們收集的Dupixent臨床數據支持一種統一的分子機制，該機制與氣喘、異位性皮膚炎、鼻息肉、結節性癢疹以及嗜酸性食道炎等相關疾病密切相關。根據這個統一的假設，IL-4和IL-13誘導的發炎在不同的組織隔間中驅動著所有這些相關疾病的發生和發展。

Moving to Libtayo in oncology. In the third quarter, our robust oncology pipeline has started to deliver data readouts from our latest and most innovative programs, and we are expecting these readouts to accelerate in the remainder of 2022 and continuing to 2023. The European Society of Medical Oncology, or ESMO, Annual Meeting in September, was truly a banner event for Regeneron with several notable oral presentations for assets in our oncology pipeline, which I'd like to briefly summarize.

在腫瘤領域，我們轉向Libtayo。第三季度，我們強大的腫瘤產品線已開始公佈最新、最具創新性的項目的臨床數據，我們預計這些數據將在2022年剩餘時間和2023年加速發布。 9月舉行的歐洲腫瘤內科學會（ESMO）年會對於Regeneron而言可謂是一次盛會，我們在會上就腫瘤產品線中的多個重要項目進行了口頭報告，我將在此簡要概述一下。

Starting with Fianlimab our LAG-3 antibody in combination with Libtayo. At ESMO, we shared data from 2 independent advanced melanoma expansion cohorts from our first-in-human study, which importantly showed consistent efficacy and safety between the 2 replicate cohorts. Fianlimab in combination with Libtayo demonstrated greater than 60% response rates in each cohort, a median PFS estimated to be 24 months across both cohorts and a median duration of response that had not yet been reached. The preliminary safety profile of the combination appears to be in line with anti-PD-1 monotherapy and potentially with less toxicity compared to anti-CTLA-4 combinations.

首先介紹的是Fianlimab（我們的LAG-3抗體）與Libtayo的聯合療法。在ESMO大會上，我們分享了來自首次人體試驗的兩個獨立的晚期黑色素瘤擴展隊列的數據，重要的是，這兩個重複隊列均顯示出一致的療效和安全性。 Fianlimab聯合Libtayo在每個隊列中均顯示超過60%的客觀緩解率，兩個隊列的中位無進展生存期（PFS）估計為24個月，中位緩解持續時間尚未達到。此聯合療法的初步安全性似乎與抗PD-1單藥療法相當，並且可能比抗CTLA-4聯合療法毒性更低。

While dual LAG-3 and PD-1 inhibition has previously shown promise in advanced melanoma, response rates greater than 45% with median PFS of more than a year had not been previously reported. These initial results in melanoma suggest that Fianlimab-Libtayo combination has a potentially best-in-class profile in this setting. We are enrolling our Phase III metastatic melanoma study -- we intend to initiate a Phase III adjuvant melanoma study later this year and have additional plans in other solid tumors where Fianlimab has the potential to be first-in-class.

儘管LAG-3和PD-1雙重抑制先前已在晚期黑色素瘤中展現出療效，但此前尚未報道過緩解率超過45%且中位無進展生存期超過一年的病例。這些在黑色素瘤中的初步結果表明，Fianlimab-Libtayo聯合療法在該適應症中可能具有同類最佳的療效。我們正在進行轉移性黑色素瘤的III期臨床研究，並計劃於今年稍後啟動一項III期輔助治療黑色素瘤研究。此外，我們也計劃在其他實體瘤領域進行Fianlimab的臨床試驗，以期在該領域成為同類首創療法。

The neoadjuvant cutaneous squamous cell carcinoma, or CSCC, a Phase II study of Libtayo monotherapy has shown promising results. Given prior to potentially curative surgery in patients with large tumors Libtayo was able to deliver major pathological responses to 63% of patients prior to surgery. This raises the possibility that Libtayo could decrease the burden of these major and potentially disfiguring surgeries for the many patients who require them each year. We are pleased that concurrent with the ESMO presentation, these data were published in the New England Journal of Medicine.

一項針對新輔助治療皮膚鱗狀細胞癌（CSCC）的Libtayo單藥治療II期研究顯示出令人鼓舞的結果。在腫瘤較大的患者接受可能治癒的手術前給予Libtayo治療，63%的患者在術前即獲得了顯著的病理緩解。這表明Libtayo有可能減輕每年眾多需要接受此類大型且可能導致毀容手術的患者所承受的負擔。我們欣喜地看到，這些數據與ESMO會議報告同時發表於《新英格蘭醫學雜誌》。

Regarding next steps, we are talking to regulators about possible pathways for labeling and potential inclusion in the NCCN guidelines. Also at ESMO, we presented initial clinical data for Ubamatamab and our MUC16xCD3 bispecific developed for advanced ovarian cancer, our first clinical data for a CD3 bispecific in a solid tumor. In heavily pretreated ovarian cancer population, we observed durable responses to this MUC16xCD3 monotherapy in a patient subset whose tumors overexpressed MUC16, response rates were as high as 31%. Most of the treatment of Vergent adverse events occurred with the initial step-up dosing. Ubamatamab is being developed as a monotherapy as well as in combination with Libtayo as well as in combination with our MUC16 costim bispecific. We are looking forward to more data across these programs in 2023.

關於後續步驟，我們正在與監管機構探討可能的標籤審批途徑以及納入NCCN指南的可能性。此外，在ESMO大會上，我們公佈了Ubamatamab和我們開發的用於治療晚期卵巢癌的MUC16xCD3雙特異性抗體的初步臨床數據，這是我們首個用於治療實體瘤的CD3雙特異性抗體的臨床數據。在先前接受過大量治療的卵巢癌患者中，我們觀察到MUC16xCD3單藥治療在腫瘤MUC16過度表現的患者亞群中具有持久療效，緩解率高達31%。 Vergent治療的大部分不良事件發生在初始劑量遞增階段。 Ubamatamab正在開發作為單藥療法，以及與Libtayo聯合用藥和與我們的MUC16 cosim雙特異性抗體聯合用藥。我們期待在2023年獲得這些項目的更多數據。

In our ESMO investor presentation, we shared more detailed data for a PSMA by CD28 costim bispecific in combination with Libtayo representing the first efficacy and safety data for this new class of bispecifics, which we had initially top lined and discussed at our second quarter earnings. We have since continued to enroll patients in this study, and we are planning to present updated data at a medical meeting in the first half of 2023.

在ESMO投資人報告中，我們分享了PSMA/CD28共刺激雙特異性抗體合併Libtayo的更詳細數據，這是該類新型雙特異性抗體的首個療效和安全性數據。我們曾在第二季財報中初步介紹並討論過該類抗體。此後，我們繼續招募患者參與這項研究，並計劃在2023年上半年的醫學會議上公佈更新後的數據。

Regarding our hem/onc pipeline, we are looking forward to data from odronextamab. -- our CD20 x CD3 bispecific as well as linvoseltamab, our BCMA by CD3 bispecific at the American Society of Hematology or ASH Annual Meeting in December. For odronextamab, we will present pivotal Phase II data for both follicular lymphoma and diffuse large B-cell lymphoma in 2 separate oral presentations. Upon discussions with the FDA, we are now targeting a second half 2020 regulatory filing for this program. We hope to initiate combination studies with an appropriate CD20 costim bispecific in the near future.

關於我們的血液/腫瘤產品線，我們期待在12月舉行的美國血液學會（ASH）年會上公佈odronextamab（一種CD20×CD3雙特異性抗體）以及linvoseltamab（一種BCMA×CD3雙特異性抗體）的數據。我們將分別以口頭報告的形式，展示odronextamab在濾泡性淋巴瘤和瀰漫性大B細胞淋巴瘤治療中的關鍵性II期臨床數據。經與FDA討論，我們目前計劃在2020年下半年提交該項目的監管申請。我們希望在不久的將來啟動與合適的CD20共刺激雙特異性抗體的聯合用藥研究。

For linvoseltamab, our BCMAxCD3 bispecific antibody remained on track with development and are planning to file pending discussions with the FDA in 2023. We have now completed enrollment in our potentially pivotal Phase II study. As I mentioned earlier, data from this study will be updated at ASH.

對於linvoseltamab，我們的BCMAxCD3雙特異性抗體研發進展順利，並計劃於2023年向FDA提交待決的核准文件。我們目前已完成一項可能具有關鍵意義的II期臨床試驗的患者招募。正如我之前提到的，該研究的數據將在ASH會議上更新。

As with odronextamab,we are planning on initiating combination studies for linvoseltamab with co-stimulatory bispecifics in the near future. We believe existing standard of care therapies leave significant room for improvement in these difficult-to-treat settings, and we have been encouraged by the interim efficacy and safety data we have generated to date for both odronextamab and linvoseltamab.

與 odronextamab 一樣，我們計劃在不久的將來啟動 linvoseltamab 與共刺激雙特異性抗體的聯合用藥研究。我們認為，在這些難治性疾病中，現有的標準治療方案仍有很大的改進空間，而迄今為止，我們獲得的 odronextamab 和 linvoseltamab 的中期療效和安全性數據都令我們感到鼓舞。

Finally, at ESMA, we also shared initial data for our METxMET bispecific antibody in MET-altered non-small cell lung cancer. Responses were enriched in patients with higher levels of met expression. No dose-limiting toxicities were observed. Even the modest overexpression of MET may render lung cancer susceptible to this mechanism of action and we're looking forward to the METxMET antibody drug conjugate data next year.

最後，在ESMA會議上，我們也分享了METxMET雙特異性抗體在MET基因改變的非小細胞肺癌的初步數據。 MET表現量較高的患者療效較佳。未觀察到劑量限制性毒性。即使是MET的輕微過度表現也可能使肺癌對這種作用機制敏感，我們期待明年獲得METxMET抗體藥物偶聯物的數據。

In summary for oncology, a rich commentator of the pipeline is delivering competitive data. And with our full ownership of Libtayo, we're excited about the potential to advance standard of care in oncology with our portfolio approach.

總而言之，在腫瘤領域，我們擁有豐富的研發管線數據，​​並且取得了顯著的成效。憑藉我們對Libtayo的全資所有權，我們對透過產品組合策略提升腫瘤治療標準充滿信心。

Concluding with the Regeneron Genetic Medicines efforts, where we continue to progress our pipeline and discovery engine. In September, we and Alnylam reported promising data from our ongoing Phase I study of Alnylam HSD in nonalcoholic steatohepatitis or NASH. -- we are planning on initiating a Phase II study shortly, which is just one part of our multipronged approach, exploring multiple genetically validated targets for NASH.

最後，我們來談談Regeneron基因藥物業務，我們將繼續推動產品線和研發進程。今年9月，我們與Alnylam公司共同公佈了正在進行的Alnylam HSD治療非酒精性脂肪性肝炎（NASH）的I期臨床試驗的初步數據，結果令人鼓舞。我們計劃近期啟動II期臨床試驗，這只是我們多管齊下策略的一部分，該策略旨在探索多個經基因驗證的NASH標靶。

Also in September, we and Intellia announced initial data from the cardiomyopathy arm of our ongoing Phase I study of NTLA-2001, an investigational CRISPR-based therapy for the treatment of transthyretin amyloidosis, which show deep and sustained mean serum TTR reductions of over 90% and was generally well tolerated. Finally, in October, our collaborators a decibel Therapeutics announced FDA clearance for an NDA application for DB-OTO, our first virally delivered gene therapy product candidate designed to provide hearing to individuals with otoferlin-related hearing loss. This IND provides clearance to initiate a pediatric Phase I/II clinical trial in the United States.

同樣在9月，我們和Intellia公佈了正在進行的NTLA-2001 I期臨床試驗中心肌病變組的初步數據。 NTLA-2001是一種基於CRISPR技術的在研療法，用於治療轉甲狀腺素蛋白澱粉樣變性。數據顯示，NTLA-2001可使血清TTR平均顯著且持續降低90%以上，且整體耐受性良好。最後，在10月，我們的合作夥伴decibel Therapeutics宣布，我們首個病毒載體基因治療候選產品DB-OTO的新藥申請（IND）已獲得FDA批准。 DB-OTO旨在幫助患有耳蛋白相關聽力損失的患者恢復聽力。此IND申請獲准在美國啟動一項兒科I/II期臨床試驗。

With that, I will turn it over to Marion.

接下來，我將把任務交給瑪莉安。

Thank you, George. Our third quarter performance reflects strength in growth across our commercial portfolio. We continue to extend our leadership position in additional therapeutic categories is part of our commitment to deliver life-changing medicines to patients in need. With Dupixent's approval in prurigo nodularis, Libtayo's anticipated approval in combination with chemotherapy in first line advanced non-small cell lung cancer and recent data demonstrating the compelling profile of aflibercept 8-milligram Regeneron's commercial business is poised to deliver long-term growth.

謝謝喬治。我們第三季的業績反映了我們商業產品組合的強勁成長動能。我們不斷鞏固在更多治療領域的領先地位，這是我們致力於為有需要的患者提供改變生命的藥物的承諾的一部分。隨著Dupixent核准用於治療結節性癢疹，Libtayo有望獲批與化療聯合用於一線治療晚期非小細胞肺癌，以及近期數據顯示8毫克阿柏西普具有顯著療效，Regeneron的商業業務有望實現長期增長。

Starting with EYLEA, which reached $2.4 billion in global net sales for the third quarter. This represents an 8% increase on a constant currency basis, a remarkable achievement for a brand that launched 11 years ago. In the U.S., EYLEA net sales grew 11% year-over-year to $1.63 billion to again achieve over 1 million injections in the quarter. despite the overall 2% sequential category decline in volume from the second to third quarter of 2022,

首先來看安禮 (EYLEA)，第三季全球淨銷售額達到 24 億美元。以固定匯率計算，這相當於成長了 8%，對於一個 11 年前創立的品牌來說，這是一個了不起的成就。在美國，安禮的淨銷售額年增 11%，達到 16.3 億美元，本季注射量再次突破 100 萬支。儘管 2022 年第二季至第三季度，整個品類的銷量較上月下降了 2%，但安禮的業績依然亮眼。

EYLEA continued to grow across all indications, gaining share from both branded and unbranded agents. In fact, EYLEA reached all-time highs in category share of approximately 50%, with a commanding 75% share in the branded category. We continue to strengthen and extend EYLEA's leadership position in the anti-VEGF category.

EYLEA在所有適應症領域持續成長，從品牌藥和非品牌藥手中奪取了市場份額。事實上，EYLEA的市佔率達到了約50%的歷史新高，在品牌藥領域更是佔了75%的領先地位。我們將繼續鞏固和擴大EYLEA在抗VEGF領域的領先地位。

As we recently announced, the FDA has granted pediatric exclusivity for EYLEA, thereby extending the period of EYLEA U.S. market exclusivity by an additional 6 months through May 17, 2024. Since announcing positive Phase III results earlier this year, there's been widespread excitement in the retina community about the aflibercept 8-milligram data set and aflibercept 8-milligrams potential to become the future standard of care if approved.

正如我們最近宣布的那樣，FDA 已授予 EYLEA 兒科獨佔權，從而將 EYLEA 在美國的市場獨佔期延長 6 個月至 2024 年 5 月 17 日。自今年稍早公佈積極的 III 期臨床試驗結果以來，視網膜領域對阿柏西普 8 毫克的數據以及阿柏西普 8 毫克如果獲得批准可能成為未來標準療法的潛力感到普遍興奮。

Next to Libtayo. Total global product sales were $143 million, growing 25% on a constant currency basis. In the U.S., net sales grew 21% to $95 million based on growth in our lung and non-melanoma skin indications. We see particular opportunity for growth in lung cancer over time. In monotherapy, there are already steady increases in prescribers and total utilization. We are launch-ready for the potential chemotherapy combination approval, which significantly expands the patient opportunity.

僅次於利妥昔單抗（Libtayo）。全球產品總銷售額達1.43億美元，以固定匯率計算成長25%。在美國，淨銷售額成長21%至9,500萬美元，主要得益於肺癌和非黑色素瘤皮膚適應症的成長。我們認為，肺癌領域未來具有巨大的成長潛力。在單藥治療方面，處方醫師數量和總使用量均呈現穩定成長的趨勢。我們已做好上市準備，一旦化療合併用藥獲得批准，將顯著擴大患者的治療機會。

And finally, to Dupixent, third quarter global net sales were $2.3 billion, up 45% on a constant currency basis. In the U.S., net sales grew 45% to $1.82 billion, driven by robust demand across atopic dermatitis, asthma and nasal polyps. Growth was also driven by a rapid launch trajectory across recent indications, including Eosinophilic Esophagitis and pediatric atopic dermatitis where Dupixent is the only biologic to be approved from infancy through adulthood. Starting with dermatology and atopic dermatitis, Dupixent is the leading first-line systemic therapy with strong uptake across the spectrum of moderate to severe disease and across age groups. The ongoing launch in children as young as 6 months is progressing very well, providing relief to children and their families as well as reinforcing the safety of Dupixent for all age groups. We have also expanded Dupixent's leadership in dermatology following its approval in prurigo nodularis. Dupixent is the only FDA-approved medicine for this chronic debilitating skin disease that affects approximately 75,000 adults in the U.S. Early launch indicators are positive with patients already being initiated on therapy.

最後，Dupixent第三季全球淨銷售額達23億美元，以固定匯率計算成長45%。在美國，淨銷售額成長45%至18.2億美元，主要得益於異位性皮膚炎、氣喘和鼻息肉治療領域的強勁需求。此外，Dupixent近期在包括嗜酸性食道炎和兒童異位性皮膚炎在內的多個適應症領域快速上市，也推動了銷售額的成長。在兒童異位性皮膚炎領域，Dupixent是唯一獲準用於嬰幼兒至成人的生物製劑。 Dupixent最初應用於皮膚病和異位性皮膚炎治療，目前已成為領先的一線全身治療藥物，在中重度疾病和各個年齡段均獲得了廣泛應用。目前正在進行的6個月及以上嬰兒的上市進展順利，不僅為患兒及其家庭帶來了福音，也進一步證實了Dupixent對所有年齡層的安全性。 Dupixent獲準用於治療結節性癢疹後，進一步鞏固了其在皮膚病領域的領先地位。 Dupixent是目前唯一獲得FDA核准用於治療這種慢性致殘性皮膚病的藥物，在美國影響約75,000名成年人。早期上市指標顯示，患者已開始接受治療，療效良好。

Dupixent also continued to perform well in the highly competitive asthma market with steady growth in prescriptions and new patient starts as well as in nasal polyps. Early launch performance in the Eosinophilic Esophagitis has been very strong, with broad adoption from both gastroenterologists and allergists. The medical community has embraced Dupixent as patients previously had very limited options Dupixent is the only medicine indicated to treat Eosinophilic Esophagitis and is the only treatment shown to address the underlying disease causes resulting in unprecedented symptom relief. There are approximately 50,000 adults in adolescent patients in the U.S., and we continue to advance our clinical efforts in younger patients where substantial unmet need remains. Outside the U.S. Dupixent net sales were $506 million, growing 44% on a constant currency basis. There is rapid uptake across approved indications, and we continue to execute on recent launches and expand into new geographies. As part of this, Regeneron's increased presence in key international markets supports efforts to bring Dupixent to even more patients.

在競爭激烈的氣喘市場，Dupixent 也持續表現良好，處方量和新患者數量穩定成長，鼻息肉治療方面也是如此。 Dupixent 在嗜酸性粒細胞性食道炎的早期上市表現非常強勁，並獲得了胃腸病學家和過敏科醫生的廣泛認可。由於患者先前治療選擇非常有限，Dupixent 已獲得醫學界的廣泛認可。 Dupixent 是目前唯一獲準用於治療嗜酸性粒細胞性食道炎的藥物，也是唯一被證實能夠解決根本病因並帶來前所未有的症狀緩解的療法。在美國，約有 5 萬名成人和青少年患者，我們將繼續推進年輕患者族群的臨床研究，以滿足他們尚未充分滿足的醫療需求。在美國以外，Dupixent 的淨銷售額為 5.06 億美元，以固定匯率計算成長了 44%。 Dupixent 在已核准的適應症中均取得了快速成長，我們將繼續推動近期上市的藥物，並拓展新的市場。作為其中的一部分，Regeneron 在關鍵國際市場的業務不斷拓展，有助於將 Dupixent 帶給更多患者。

In conclusion, our third quarter performance demonstrates strength and growth across our commercial portfolio. We are successfully executing on initiatives to deliver life-changing medicines to patients and advancing strategies to maximize new and upcoming launches. Our commercial portfolio is positioned well to drive long-term and sustainable growth.

總之，我們第三季的業績展現了我們商業產品組合的強勁勢頭和成長勢頭。我們正成功地推動各項舉措，為患者提供改變生命的藥物，並積極推動各項策略，以最大限度地提升新產品和即將上市產品的市場效益。我們的商業產品組合已做好充分準備，推動長期可持續成長。

Now I'll turn the call to Bob.

現在我把電話轉給鮑伯。

Thank you, Marion. My comments today on Regeneron's financial results and outlook will be on a non-GAAP basis unless otherwise noted. Regeneron performed well in the third quarter, with growth from key brands and execution across the business, continuing to drive strong financial results on both the top and bottom line. Excluding global revenues related to the COVID-19 antibody cocktail, third quarter total revenues increased 11% year-over-year to $2.9 billion, demonstrating continued growth momentum from our core business in reflecting the favorable impact of the Libtayo transaction.

謝謝，Marion。除非另有說明，我今天對Regeneron財務業績和展望的評論將基於非GAAP準則。 Regeneron第三季表現良好，主要品牌的成長和業務各環節的執行力持續推動營收和利潤雙雙強勁成長。剔除與新冠病毒抗體雞尾酒療法相關的全球收入，第三季總收入年增11%至29億美元，這體現了我們核心業務的持續成長勢頭，也反映了Libtayo交易帶來的正面影響。

Third quarter total diluted net income per share was $11.14 on net income of $1.3 billion. Beginning with collaboration revenue and starting with Bayer. Third quarter 2022 ex U.S. EYLEA net product sales were $817 million, up 4% on a constant currency basis versus third quarter 2021. Total Bayer collaboration revenue was $333 million, of which $315 million related to our share of EYLEA net profits outside the U.S. Total Sanofi collaboration revenue was $711 million in the third quarter of 2022 and grew 22% from the prior year, driven by Dupixent.

第三季稀釋後每股淨收益為11.14美元，淨利為13億美元。以上數據均包含合作收入，且首先來自拜耳。 2022年第三季（不含美國），EYLEA淨產品銷售額為8.17億美元，以固定匯率計算較2021年第三季成長4%。拜耳合作總收入為3.33億美元，其中3.15億美元與我們在美國以外地區EYLEA淨利的份額有關。 2022年第三季度，賽諾菲合作總營收為7.11億美元，較上年同期成長22%，主要得益於Dupixent的強勁表現。

Recall that in connection with the Libtayo transaction, we increased the repayment of our antibody collaboration development balance from 10% to 20% of antibody collaboration profits, A portion of this step-up is recorded as a reduction to antibody collaboration revenues, while another portion is recorded as R&D expense. Given Regeneron is now recording its full 50% share of antibody collaboration R&D expense as incurred. Previously, Regeneron had only recognized a partial share of its antibody collaboration R&D expenses as incurred, with the remaining share of expenses added to the antibody development balance.

回顧一下，在Libtayo交易中，我們將抗體合作開發餘額的償還比例從抗體合作利潤的10%提高到20%。這一比例的提高一部分計入抗體合作收入的減少額，另一部分則計入研發費用。鑑於Regeneron目前已將其應承擔的50%抗體合作研發費用全部計入發生額。此前，Regeneron僅將部分抗體合作研發費用計入發生額，剩餘部分則計入抗體開發餘額。

Also, as we highlighted last quarter and in accordance with the agreement, we recorded a onetime development balance repayment of $57 million as an incremental reduction to Sanofi collaboration revenue in the third quarter of 2022. We have posted to our website supporting materials to further explain the accounting associated with this and other elements of the Libtayo transaction.

此外，正如我們上季度重點強調的，根據協議，我們在2022年第三季度計入了一次性開發餘額償還款5700萬美元，作為賽諾菲合作收入的增量減少。我們已在網站上發布了相關資料，以進一步解釋與此及Libtayo交易其他要素相關的會計處理。

Moving now to our operating expenses. R&D increased 38% year-over-year to $817 million, partially driven by the impact of the Libtayo transaction, which affects R&D in 2 ways. First, Regeneron now records all R&D expense for Libtayo, which was previously shared equally with Sanofi. Second, as I mentioned earlier, Regeneron now records our full 50% share of antibody collaboration spend for Dupixent and itepekimab.

接下來談談我們的營運費用。研發費用年增38%至8.17億美元，部分原因是Libtayo交易的影響，該交易對研發產生兩方面的影響。首先，Regeneron現在將Libtayo的全部研發費用計入公司帳目，而此前這部分費用是與賽諾菲平均分攤的。其次，正如我之前提到的，Regeneron現在將Dupixent和itepekimab抗體合作研發支出中我們應承擔的全部50%份額計入公司帳目。

SG&A expense increased 20% year-over-year to $467 million primarily driven due to incremental cost related to assuming global rights to Libtayo. Cost of goods sold in the third quarter was $109 million, and product gross margin in the quarter increased but 94% as compared to 90.2% in the prior year. The more favorable gross margin was driven by the non-recurrence of REGEN-COV sales in the current period in the removal of the payment to Sanofi for their share of U.S. Libtayo gross margin. Finally, the third quarter 2022 effective tax rate was 12.1% compared to 10.8% in the prior year.

銷售、管理及行政費用年增20%至4.67億美元，主要原因是承接Libtayo全球權益相關的額外成本。第三季銷售成本為1.09億美元，產品毛利率為94%，高於去年同期的90.2%。毛利率的提高主要得益於本期REGEN-COV銷售額不再重複，從而免除了向賽諾菲支付其在美國Libtayo毛利率中所佔份額的費用。最後，2022年第三季實際稅率為12.1%，高於去年同期的10.8%。

Shifting now to cash flow and the balance sheet. Year-to-date in 2022, Regeneron has generated $2.9 billion in free cash flow and ended the third quarter of 2022 with cash and marketable securities less debt of approximately $10.3 billion. We remain focused on leveraging our strong financial position to deliver long-term value for shareholders. Over the first 9 months of 2022, we have deployed in excess of $2.8 billion in capital. We have executed approximately $1.2 billion in business development initiatives, including the $900 million acquisition of Libtayo rights. Additionally, we have repurchased over $1.6 billion of our shares including over $900 million in the third quarter alone. As of September 30, we had approximately $1.2 billion remaining on our current share repurchase authorization, and we remain opportunistic buyers.

現在我們來看現金流和資產負債表。 2022年至今，Regeneron已產生29億美元的自由現金流，截至2022年第三季末，公司現金及有價證券減去債務約103億美元。我們將繼續專注於利用自身穩健的財務狀況，為股東創造長期價值。 2022年前9個月，我們已投入超過28億美元的資金。我們已執行約12億美元的業務拓展計劃，其中包括以9億美元收購Libtayo的權益。此外，我們已回購超過16億美元的股票，光是第三季就回購了超過9億美元。截至9月30日，我們目前的股票回購授權額度還剩約12億美元，我們仍將積極尋找合適的收購機會。

As we approach the end of the year, we've made some minor changes to our 2022 guidance ranges. A complete summary of our latest full year financial guidance is available in our press release issued earlier this morning.

隨著年底臨近，我們對2022年的業績預期範圍進行了一些微調。完整的全年財務預期摘要已發佈在今天早些時候的新聞稿中。

In addition to these changes, I would also like to provide some initial thoughts on our 2023 expense outlook. We continue to make investments to advance our pipeline and position the company for long-term growth. We expect R&D investment to grow in 2023 comparable to or slightly above the 9-month year-to-date growth rate reported earlier today. The incremental R&D investment in 2023 will be driven by advancing our immuno-oncology, hematology, immunology and genetic medicine pipeline as well as the continued expansion of our R&D organization.

除了上述調整之外，我還想就我們2023年的支出展望做一些初步說明。我們將繼續加大投資，推動產品線研發，為公司的長期成長奠定基礎。我們預計2023年的研發投入將與今天稍早公佈的今年前9個月的成長率持平或略高。 2023年研發投入的增加將主要得益於我們在免疫腫瘤學、血液學、免疫學和基因藥物領域的產品線推進，以及研發團隊的持續擴張。

In addition, 2023 will be the first full year reflecting the impact of the Libtayo transaction where we record a 100% of the global R&D spend for Libtayo and our full 50% share of the Sanofi antibody collaboration R&D spend as incurred.

此外，2023 年將是反映 Libtayo 交易影響的第一個完整年度，屆時我們將記錄 Libtayo 全球研發支出的 100% 以及我們在賽諾菲抗體合作研發支出中 50% 的全部份額。

For SG&A in 2023, we currently project growth in the mid-teens versus 2022, given we'll be recording a full year of global Libtayo expenses, along with targeted investments in the build-out of our international infrastructure.

鑑於我們將記錄一整年的 Libtayo 全球支出，以及對國際基礎建設的專項投資，我們目前預計 2023 年的銷售、一般及行政費用將比 2022 年增長 15% 左右。

Finally, for other operating income and expense in the third quarter of 2022, we recognized the remaining $44 million of deferred income related to previously received upfront payments and development milestones for Fasinumab as a result of the program's discontinuation. We do not currently expect any material other operating income or expense in the fourth quarter of 2022 in 2023 and beyond absent any new transactions.

最後，關於2022年第三季的其他營業收入和支出，我們確認了與Fasinumab專案終止相關的剩餘4,400萬美元遞延收入，與先前收到的預付款和研發里程碑付款有關。目前，我們預計在2022年第四季、2023年及以後，如果沒有新的交易，不會出現任何重大的其他營業收入或支出。

In conclusion, Regeneron has performed exceptionally well in the first 9 months of 2022, and our strong financial position enables continued investment to drive long-term growth.

總而言之，Regeneron 在 2022 年前 9 個月表現非常出色，我們強勁的財務狀況使我們能夠繼續投資，推動長期成長。

With that, I will pass the call back to Ryan.

這樣，我就把電話轉回給瑞恩了。

Thank you, Bob. Towanda, this concludes our prepared remarks. We'd now like to open the call for Q&A with the number of callers in the queue, I'd like to ensure we are able to address as many questions as possible. As a result, we'll only be able to answer one question from each caller before moving to the next. Towanda, please open the call for Q&A.

謝謝鮑勃。托萬達，我們的演講到此結束。現在我們開始問答環節。鑑於排隊人數眾多，為了確保我們能夠回答盡可能多的問題，我們只能回答每位來電者的一個問題，然後才會輪到下一位。托萬達，請開始問答環節。

(Operator Instructions)

（操作說明）

Our first question comes from the line of Evan Seigerman with BMO.

我們的第一個問題來自 BMO 的 Evan Seigerman。

Congrats on the progress. So with nearly $13 billion on the balance sheet, and minimal debt. Can you provide more color on your capital allocation priorities? Would you consider business development on a larger scale and are issuing a dividend?

恭喜取得的進展。目前公司資產負債表上擁有近130億美元的資金，負債極低。能否詳細說明一下您的資本配置重點？您是否考慮擴大業務規模並派發股息？

It's Bob. With regards to capital allocation, demonstrated today by our growth in R&D and the 2023 forward guidance, we are going to continue to invest, first and foremost, in the R&D pipeline that we have we issued our 10-Q this morning. Within the MD&A, you'll see a plethora of trials that are currently ongoing. And as George mentioned in his script, we're very bullish with regards to what is in the pipeline. Now again, with regards to business development, it's not an end or an or, right? As you saw and what we've done in the first 9 months of 2022, where we do think there are opportunities and where we do think we can do collaborations where 1 plus 1 is 3, then we're absolutely going to take that opportunity.

我是鮑伯。關於資本配置，正如我們今天在研發方面的成長以及2023年的前瞻性指引所表明的那樣，我們將繼續優先投資於我們現有的研發管線，我們今天早上已經發布了10-Q報告。在管理階層討論與分析（MD&A）部分，您會看到目前正在進行的大量試驗。正如喬治在他的演講稿中提到的，我們對管線中的項目非常樂觀。再說一遍，關於業務拓展，這並非一個終點或二選一的問題，對吧？正如您所看到的，以及我們在2022年前9個月所做的工作，如果我們認為存在機會，並且我們認為可以開展合作，實現1+1>3的效益，那麼我們絕對會抓住這些機會。

And I think Checkmate was a good example of that. I would expect that you'd see more of that. With regards to your question on dividends, it's never an never. Obviously, that tool is in our tool chest. If we do decide to play that card as of right now, we don't have dividends in the foreseeable future in our plan. We have been very opportunistic with regards to buybacks. Again, the MD&A issued earlier today. The 10-Q will show you what we've been buying back our shares. Again, we'll remain opportunistic buyers, and we do have a remaining $1.2 billion remaining under our current $3 billion authorization.

我認為「將軍」（Checkmate）就是一個很好的例子。我預計你會看到更多類似的案例。關於你提到的分紅問題，這並非絕對。顯然，分紅是我們工具箱裡的一個工具。如果我們現在決定派發股息，那麼在可預見的未來，我們的計劃中不會包含分紅。我們在股票回購方面一直非常積極。今天稍早發布的管理層討論與分析（MD&A）以及10-Q表格會詳細列出我們的股票回購情況。我們將繼續保持積極的回購策略，目前我們30億美元的授權額度下還有12億美元剩餘。

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

我們的下一個問題來自泰勒·範·布倫和考恩的系列。

Congratulations on the great quarter. So I just pulled up the odronextamab and 5458 ASH abstracts. And It'd be great to get a brief preview from you guys and what you need -- what you believe you ultimately need to show at the conference to be competitive relative to what others have shown.

恭喜你們本季表現出色。我剛剛調了 odronextamab 和 5458 ASH 的摘要。如果你們能簡單介紹一下情況，以及你們需要做些什麼——你們認為最終需要在會議上展示哪些內容才能在與其他與會者的競爭中脫穎而出——那就太好了。

I don't think we want to stoop ourselves given that the conference is coming up pretty soon, Tyler. But odronextamab has the potential of being a very important molecule. We recognize that there are some people ahead of us. And we recognize that some of the most recent time lines have pushed back a little bit based on recent regulatory feedback. The regulators have recently been focused on having Phase III trials substantially enrolled at the time of submission before they'll grant accelerated approval. But we are confident in the profile of odronextamab and as George says, there's also the future possibility of combinations with other things in our pipeline that could really even lead for us.

泰勒，鑑於會議即將召開，我認為我們不能妄自菲薄。但odronextamab確實有可能成為一個非常重要的分子。我們意識到，目前還有一些公司走在我們前面。我們也意識到，根據最近的監管回饋，一些最新的時間表有所延遲。監管機構最近一直關注的是，在提交申請之前，III期臨床試驗的入組人數必須達到一定規模，才會批准加速審批。但我們對odronextamab的特性充滿信心，正如喬治所說，它未來還有可能與我們研發管線中的其他藥物合併使用，這甚至可能成為我們未來的突破性進展。

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

我們的下一個問題來自高盛的薩爾文·里希特。

On EYLEA, what are you observing in the market between yourselves and Roche for the business launch?

關於安永，您和羅氏在市場方面對安永的業務拓展有何觀察？

So happy to give more characterization. As I mentioned, we see EYLEA continuing to perform extremely well, reaching all-time high, category share 50% and now as well growth in the overall branded market where we participate with other branded agents, including Roche. One thing I will mention, just to give a bit more insight is that EYLEA captured growth coming primarily from Lucentis and also from Avastin. And in fact, if you put the Roche portfolio together, the growth of EYLEA, obviously, was positive, while there was a decline in overall market share for the Roche products combined.

很高興能提供更多細節。正如我之前提到的，安怡（EYLEA）的表現持續非常出色，市場份額達到歷史新高，高達50%，並且在我們與其他品牌代理商（包括羅氏）共同參與的整個品牌市場中也實現了增長。我想補充一點，以便更深入地了解情況，安怡的增長主要來自盧森蒂斯（Lucentis）和阿瓦斯汀（Avastin）。事實上，如果將羅氏的產品組合放在一起比較，安怡的成長顯然是正的，而羅氏所有產品的整體市佔率卻有所下降。

Our next question comes from the line of Matthew Harrison with Morgan Stanley.

我們的下一個問題來自摩根士丹利的馬修·哈里森。

George, I was wondering if you could just comment on your outlook for the COPD study for Dupixent and how you think about that market opportunity?

喬治，我想請你談談你對Dupixent治療COPD的研究前景的看法，以及你如何看待這個市場機會？

Obviously, COPD has been a very difficult disease for new therapies and biologics, in particular, we think that there's a category of patients with COPD who have or are marked by more what we call Th2 type inflammation, we think that, as I said in my remarks, that there's this unifying hypothesis that there are a lot of TH2 type of diseases that manifest in different ways. We believe that this subset of patients with COPD may, may be or fit into that category and being able to benefit these patients.

顯然，慢性阻塞性肺病（COPD）一直是新療法和生物製劑研發的困難之處。我們認為，有一部分COPD患者表現出或具有更明顯的Th2型發炎特徵。正如我剛才所說，存在一個統一的假設，即許多疾病都存在Th2型炎症，只是表現形式各不相同。我們相信，這部分COPD患者可能屬於Th2型炎症，因此，我們有望幫助他們從中獲益。

(technical difficulty) terms of either reducing their exacerbations and/or improving their lung function would really make a difference to these patients. And so we're anxiously awaiting the data, and we're hopeful that we will have another set of patients where we might be able to demonstrate that Dupixent could really make a difference.

（技術難題）就減少病情惡化和/或改善肺功能而言，這些患者將受益匪淺。因此，我們正焦急地等待數據，並希望能找到另一組患者，證明度普利森特確實能夠帶來顯著療效。

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

我們的下一個問題來自 Wolfe Research 的 Tim Anderson。

Lilly will be launching lebrikizumab in '23 in atopic derm and they have data that looks comparable to Dupixent, at least in this one indication, pretty much a direct competitor although not identical on mechanism. They know the derma space because of Taltz and the positioning is going to be that they can dose every month versus Dupixent, which is every 2 weeks. So I'm wondering if you have any strong views on that product, or if you think there's going to be a total non-starter, which is pretty much the consensus view.

禮來公司將於2023年推出用於治療異位性皮膚炎的lebrikizumab，其數據看起來與Dupixent相當，至少在這一適應症上是如此。儘管作用機制不完全相同，lebrikizumab幾乎是Dupixent的直接競爭對手。禮來公司憑藉Taltz在皮膚病領域累積了豐富的經驗，其產品定位是每月給藥一次，而Dupixent則需要每兩週給藥一次。所以我想知道您對這款產品有什麼看法，或者您是否認為它會完全失敗，而這幾乎是大家的共識。

Maybe Marion can comment on it. But look, there's room for competitors in this market. we're really modestly penetrated in the opportunity. I don't think that the profile of what you say is actually going to be so far as we've seen it so far, they're all that similar we have the earliest from infancy already to Adult. That's a big deal, okay? In addition, the fact that many of these people have other comorbidities whether it be asthma or nasal polyps, for example, and they can get -- if they do have comorbidities, a single drug can treat both is a very big differentiator, so I think when you're the market leader, when you're so far ahead, when you have really a differentiated profile, you have an advantage. Obviously, Lilly is a fine company. They know what they're doing. But as I said, there's room frequently when new good drugs come to market, there is a growth of the market. We're not going after a fixed number of patients. We're actually growing those patients. Marion, I don't know if you want to add anything.

或許瑪莉安可以就此發表評論。但你看，這個市場還有競爭的空間。我們目前在這個領域的滲透率還很低。就我們目前所見，你所說的患者群體特徵其實並不完全相同，因為我們從嬰兒期到成人都有相應的藥物。這意義重大，懂​​嗎？此外，許多患者還伴隨其他疾病，例如氣喘或鼻息肉，如果他們確實有這些疾病，一種藥物就能同時治療所有疾病，這是一個非常大的差異化優勢。所以我認為，當你成為市場領導者，遙遙領先，擁有真正差異化的產品時，你就擁有了優勢。當然，禮來是一家優秀的公司，他們知道自己在做什麼。但正如我所說，當新的好藥上市時，市場通常會成長，因此也存在發展空間。我們並非瞄準固定數量的患者，而是不斷擴大我們的患者群體。瑪莉昂，我不知道你是否還有什麼要補充的。

I would just add that most of the key opinion leaders that we speak to recognize that the dual mechanism of action, the anti-IL-4 coupled with anti-IL-13 is very, very important. So certainly, efficacy shouldn't be assumed. There's also a reinforcement of the incredible efficacy that's seen for patients with moderate true severe disease. And obviously, real-world experience is compelling the administration with Dupixent is really quite straightforward. It's self administration, and we actually see there the active patient or parent involvement has been very helpful in establishing Dupixent, but certainly, as Len mentioned, expanding the education and category to bring more atopic dermatitis patients into the treatment continuum is very positive for patients and certainly for Dupixent.

我還要補充一點，我們訪談的大多數關鍵意見領袖都認為，Dupixent的雙重作用機制－抗IL-4和抗IL-13－非常重要。因此，療效當然不容忽視。此外，對於中度至重度患者，Dupixent的顯著療效也得到了進一步證實。顯然，實際應用經驗表明，Dupixent的給藥方式非常簡單。患者可以自行給藥，我們發現，患者或家長的積極參與對Dupixent的推廣應用起到了至關重要的作用。當然，正如Len所提到的，擴大教育範圍，讓更多異位性皮膚炎患者納入治療方案，對患者和Dupixent本身都大有裨益。

Not to pile on, but since -- just to add on to what Len was saying. I mean, the fact that the IL-13 have failed in these other important TH2 inflammation-driven diseases like asthma and like COPD and others right now, really does suggest that they are not fully addressing the TH2 inflammation both in any one particular disease, but also, as Len said, so many of these individuals, if you just look at our label or any label that describes these diseases, they suffer from other allergic comorbidities. And so Obviously, you can make such a difference for a patient where one drug can treat a systemic disease as opposed to treating the disease only in one of the many compartments where it manifests itself. I think this is the way I think medicine in the field should be moving. This is a systemic disease where TH2 inflammation is probably ramping in many compartments in the body you don't only want to treat it in one compartment, you want to treat the entire body. And that's what we've been showing systematically by going one disease after another with Dupixent. It works in every compartment and it broadly attacks the underlying inflammation that's related and causative in all of these diseases.

我不想再添油加醋，但既然——只是想補充Len剛才說的話。我的意思是，IL-13在其他一些重要的TH2發炎驅動疾病（例如氣喘、慢性阻塞性肺病等等）中療效不佳，這確實表明它們並沒有完全解決TH2發炎問題，無論是針對特定疾病，還是像Len說的那樣，很多患者，如果你看看我們的藥品說明書或任何描述這些疾病的說明書，都會發現他們還患有其他過敏性疾病。顯然，如果一種藥物能夠治療全身性疾病，而不是僅僅治療疾病在多個部位中的某個部位，對患者來說意義重大。我認為這才是醫學發展的方向。這是一種全身性疾病，TH2發炎可能在身體的多個部位同時加劇，你不能只治療某個部位，而應該治療整個身體。而這正是我們用Dupixent治療各種疾病所繫統性地證明的。它作用於身體的各個部位，並廣泛地攻擊與所有這些疾病相關的潛在發炎。

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 Mohit Bansal。

Congrats on the progress. If I could probe a little bit further on the comments you made about the growth of anti-VEGF market, you said it's about 4% year-over-year, seems like a bit of a slowdown from what the high growth we have seen. Could you elaborate further, do you see just one quarter. Do you see any underlying trend there? And is it because of the high growth we saw post COVID, which is tapering down? If you could help us understand that.

恭喜您的進展。關於您之前提到的抗VEGF市場成長情況，我想再深入探討。您提到該市場年增約4%，這似乎與我們之前看到的高速成長相比有所放緩。能否進一步解釋一下？您認為這只是一個季度的情況嗎？您是否看到了任何潛在的趨勢？這是否是因為新冠疫情後出現的高速成長正在放緩？如果您能幫助我們理解這一點，那就太好了。

I think it's very difficult to extrapolate one quarter. Certainly, I did mention that there had been a sequential decline of about 2% going from the second quarter into the third quarter in the overall anti-VEGF category, but I think it's really difficult to extrapolate from that. The numbers you shared on overall year-over-year growth of category at about 4% and we recognize as well, I think we'll have to see as a bit more time goes by, but it's really difficult to draw conclusions on what may or may have occurred in one quarter period.

我認為很難僅憑一個季度的數據就做出推論。誠然，我之前提到過，抗VEGF藥物整體銷售量從第二季到第三季較上季下降了約2%，但我認為很難以此為基礎來推斷。您分享的該品類年增約4%的數據，我們也意識到，我們需要觀察一段時間才能得出結論，但僅憑一個季度的數據就斷定可能發生或正在發生的事情，確實非常困難。

There's still quite a bit of room of growth in the diabetic guide disease area where we still see a decent growth there in that category.

糖尿病指南疾病領域仍有相當大的成長空間，我們仍然看到該類別有相當可觀的成長。

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

我們的下一個問題來自克里斯托弗·雷蒙德和派珀·桑德勒。

Just another question maybe on the VEGF market and EYLEA specifically. So in our checks, we get a sense that there's some docs who believe that susvimo confers differentiated efficacy, but on the other hand, there's still a sizable amount of docs who've yet to see a patient for follow-up after the first dose. Sort of just curious if in the field, you're seeing a difference in perception of susvimo by time of experience. That is any discernible change in perception of the more patient follow-up they've had?

關於VEGF市場以及EYLEA公司，我還有一個問題。我們調查發現，有些醫師認為Susvimo具有差異化療效，但另一方面，仍有相當一部分醫師尚未對接受首次注射的患者進行追蹤。我們想了解的是，在臨床實務中，醫師對Susvimo的看法是否會隨著經驗的累積而改變？也就是說，隨著追蹤患者的增多，醫師對Susvimo的看法是否會有明顯的改變？

I think it's probably best that [Roche] answer questions on what they're hearing about us. I'll just share at this point, I haven't heard characterization of that. Use is still at a low level, in fact, quite modest. I can characterize the EYLEA's performance as I did in terms of market leadership and the growth we see in our business in terms of market share and other parameters. And that is across indications and certainly substantially creating EYLEA as leader in the anti-VEGF category. And obviously, we're very enthusiastic as is the retina community, probably even more important about the possibilities and potential of aflibercept 8 milligram, if approved in the future.

我認為最好還是由羅氏公司來回答他們聽到的關於我們的傳聞。目前我只能說，我還沒聽到任何相關的評價。事實上，使用量仍然很低，相當有限。我可以像之前一樣，從市場領導地位以及我們在市場佔有率和其他指標所看到的業務成長來評價EYLEA的表現。這涵蓋了所有適應症，無疑地使EYLEA成為抗VEGF藥物的領導者。顯然，我們和視網膜疾病領域一樣，對阿柏西普8毫克（如果未來獲得批准）的前景和潛力充滿熱情，甚至可能比視網膜疾病領域更熱情。

Our next question comes from the line of Christopher Schott with UBS.

我們的下一個問題來自瑞銀集團的克里斯多福·肖特。

Congrats on the quarter. So on EYLEA in '23, was starting to see some formulary updates. So I was wondering could you just speak to how you see the market share evolving over the quarter 23 in light of the susvimo then obviously biosimilars?, and then just as we think about high-dose value in the back half of the year, anything you can say in terms of anticipated OpEx changes?

恭喜您本季業績出色。關於愛立信在2023年的業務，我們開始看到一些藥品目錄的更新。我想請您談談，考慮到舒維莫（Susvimo）以及生物相似藥的上市，您如何看待愛立信在2023年季度的市場份額變化？此外，考慮到下半年高劑量藥物的價值，您能否就預期的營運支出變化談談您的看法？

So as a start, we don't predict future market share performance. So I'm going to stay away from specifics in that area. Certainly, not only this quarter, but over several quarters, we've been able to demonstrate continuing strong performance with EYLEA as anti-VEGF category leader, and certainly, we'll continue to work on that. And as agents have entered the market, our competitive readiness abilities have been very strong. But most important, frankly, it's the profile of EYLEA, the clinical attributes, the safety of the product, the breadth of indications, ease of access for physicians and patients.

首先，我們不預測未來的市佔率表現。因此，我不會就此領域的具體細節發表意見。當然，不僅是本季度，在過去的幾個季度裡，我們已經證明，EYLEA 作為抗 VEGF 藥物的領導者，業績持續強勁，我們當然也會繼續努力。隨著其他藥物進入市場，我們的競爭準備能力也非常強大。但坦白說，最重要的是 EYLEA 的產品特性、臨床療效、安全性、適應症範圍以及醫生和患者的便利性。

But going forward, certainly, we'll be very much prepared to launch aflibercept 8 milligram. And as we get into that launch potentially with an FDA approval, we'll be able to give more characterization, but as George and Len described today, the profile we see with aflibercept 8-milligram and opinion leaders in the retina community confirm that this profile potentially has all the ingredients to become standard of care. And certainly, that's what we'll work on all the benefits of vision, coupled with safety and now this potential of substantial durability that hasn't been seen before in the category.

但展望未來，我們當然會做好充分準備推出8毫克阿柏西普。一旦獲得FDA批准，我們將能夠提供更詳細的資訊。正如George和Len今天所描述的，我們觀察到的8毫克阿柏西普的特性，以及視網膜領域意見領袖的回饋，都顯示它具備成為標準療法的全部潛力。當然，我們將繼續努力，充分發揮其在改善視力、確保安全性以及展現出前所未有的持久療效方面的優勢。

Colin, it's Bob. With regards to OpEx, I mean Marion and I will do what we always do on the brands. We'll look at what totally makes sense. I mean, as you know, it's kind of a defined number of retinal docs. So it's not as if we're going into a tremendously new area that creates a lot of new touch points on it. And on top of that, Marion's team right now is a very tight functioning sales rep team on the top of their game. So again, we don't expect some gigantic pivots in this area. But again, we will make sure that we fund this appropriately and that it is the commercial side of it is going to match how well the clinical data is going to stand up on it.

科林，我是鮑伯。關於營運支出，我和瑪莉安會像往常一樣對待品牌，我們會仔細評估哪些方案完全合理。你也知道，我們服務的視網膜科醫生數量是固定的，所以我們不是要進入一個全新的領域，需要建立很多新的聯繫點。而且，瑪莉安的團隊目前是一支非常有效率、運作良好的銷售團隊，他們都非常優秀。所以，我們預期在這個領域不會出現什麼巨大的轉變。但是，我們會確保資金投入充足，並確保商業方面的投入能夠與臨床數據相符。

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

我們的下一個問題來自 RBC 的 Brian Abrahams。

Congrats on the continued execution and innovation. On the prostate bispecific, now that you've had more time with the evolving data, any views on predictors of response or durability there? And I'm curious how your learnings might shape your latest thoughts on threading the therapeutic window, both for the PSMA as you accelerate the trial enrollment as well as your other co-stimulatory bispecifics.

恭喜你們在持續的執行和創新方面所取得的成就。關於前列腺雙特異性抗體，現在你們對不斷更新的數據有了更多了解，對於預測療效或持久性的因素有什麼看法？我很想知道，你們的最新研究成果將如何影響你們對治療窗口的掌握，無論是PSMA（正在加速臨床試驗招募）還是其他共刺激雙特異性抗體。

Yes. I think that -- our data actually shows that with the remarkable response rates we saw, especially going to the higher doses that -- it's not as if you have to look hard to find biomarkers for response. Remember, just to remind you that at the highest dose, 3 out of the 4 patients had very profound responses. So response predictors are not necessarily the issue, but you also point to the question about therapeutic window. Certainly, we are seeing autoimmune-related side effects associated with these responses.

是的。我認為——我們的數據實際上表明，鑑於我們觀察到的顯著療效，尤其是在高劑量組，尋找療效生物標記並不難。請記住，在最高劑量組中，4名患者中有3名出現了非常顯著的療效。因此，療效預測指標並非關鍵所在，但您也提到了治療窗口的問題。當然，我們也觀察到與這些療效相關的自體免疫副作用。

And so we are working hard now. We are actually -- we've accelerated enrollment in this program. We're trying to understand more the relationship between the responders and having these autoimmune side effects. I mean one, very positive perspective is we don't see these serious autoimmune side effects and people who don't see responses. So it's the people who benefit who do get the autoimmune side effects. These are obviously coupled. It's because I think the drug is doing what we intended to do. I think this is some of the most exciting data in the history of immunotherapy that you can take where people have historically called a cold tumor that has almost no responses to immunotherapy or PD-1 therapy and get these incredibly high rates of very deep and so far, durable responses.

所以我們現在正努力工作。實際上，我們已經加快了該專案的招募速度。我們正在努力更深入地了解有效應答者與自體免疫副作用之間的關係。一個非常正面的方面是，我們沒有看到那些沒有回應的患者出現嚴重的自體免疫副作用。也就是說，只有那些獲益的患者才會出現自體免疫副作用。這兩者顯然是相關的。我認為這是因為這種藥物正在發揮我們預期的作用。我認為這是免疫療法歷史上最令人振奮的數據之一，因為以往人們認為這種腫瘤是“冷腫瘤”，對免疫療法或PD-1療法幾乎沒有反應，而現在卻獲得瞭如此高比例的深度且目前為止持久的應答。

And we will continue to work on improving the therapeutic window. In terms of the bispecific program more broadly, and I want to harken back, Len sort of answered the previous question about CD20 and BCMA. But I do want to amplify on some of those comments, which is, we think that there are indeed a very small number of bispecs in the CD20 space and the BCMA space, which are actually looking quite competitive with each other, including ours. The emerging data suggests the efficacy and safety profiles of these agents will be competitive with each other. We'll see our updated data we'll presented at ASH. But I think what's emerging is that these small numbers of competitors will exist in this field.

我們將繼續致力於改善治療窗口。就雙特異性抗體計畫而言，我想再次提及Len之前關於CD20和BCMA的問題。但我希望就他的一些觀點進行補充，那就是，我們認為CD20和BCMA靶向的雙特異性抗體數量確實非常少，而且它們之間的競爭非常激烈，包括我們自己的產品。現有數據表明，這些藥物的療效和安全性將不相上下。我們將在ASH會議上公佈更新後的數據。但我認為，目前可以確定的是，這個領域將會存在著數量不多的競爭對手。

I think that there's going to be room for these. There's actually a lot of patients in these late-stage settings who need treatment. So I think that there's going to be room for these small numbers of competitors there. But the future is going to be about moving into earlier lines of therapy, and there's going to be [subtleties] there about how one executes, designs those studies, the co-therapies, more standard co-therapies that are used there. And so there's going to be a lot of actually art to how one moves these agents into the earlier lines of therapies. But the other very important thing is in addition to moving into earlier lines of therapy with these more standard combinations where, as I said, there's going to be a lot of art to doing those studies is going to be the (inaudible) combos, and as we just talked about with the CD20 and costim bispecifics that we've now shown that we're leading the field with in prostate cancer. We have very similar type agents now that we're going to be combining with our CD20 bispecific in lymphoma and with our BCMA bispecific in myeloma. And we think that these are going to really have the opportunity to continue to change the game and change the practice of medicine for these patients.

我認為這些藥物會有市場空間。實際上，很多晚期患者都需要治療。所以我認為，即使只有少數競爭者，這些藥物也有生存空間。但未來在於將治療方案擴展到更早期的治療階段，這會有很多技巧，例如如何執行、設計研究、聯合治療，以及更常用的聯合治療方案。因此，將這些藥物應用於更早的治療階段，實際上需要很多技巧。但另一個非常重要的方面是，除了將這些更常用的聯合療法應用於更早期的治療階段（正如我所說，這些研究需要很多技巧）之外，還有（聽不清）聯合療法，就像我們剛才討論的CD20和costim雙特異性抗體，我們已經證明，我們在前列腺癌領域處於領先地位。我們現在擁有非常相似的藥物，我們將把它們與用於治療淋巴瘤的CD20雙特異性抗體以及用於治療骨髓瘤的BCMA雙特異性抗體聯合使用。我們認為這些藥物將有機會真正改變治療格局，並改變這些患者的醫療實踐。

So it's about taking agents that are indeed going to be competitive and quite competitive with each other in these late-stage settings where I think they're all going to be making important contributions to the treatment of these patients, but then moving in very artful ways to these earlier lines of therapy and using them there, where I think there's also going to be room, but there's always going to be room for differentiation as well as the future. We are making these combos with all of these exciting opportunities we have in our portfolio, can really take the utilization of these agents and the treatment for these patients and these cancers to a whole another level, as we believe we're already showing that we're doing in prostate cancer.

所以，關鍵在於選擇那些在晚期治療中確實具有競爭力的藥物，我認為它們都將在晚期治療中為患者的治療做出重要貢獻。然後，巧妙地將它們應用於早期治療，我認為早期治療也存在發展空間，但未來也始終存在差異化的空間。我們正在利用我們產品組合中所有令人振奮的藥物，開發出各種聯合療法，這能夠真正將這些藥物的應用以及針對這些患者和這些癌症的治療提升到一個全新的水平，正如我們在前列腺癌領域已經展現的那樣。

George, there was one question about biomarkers in prostate cancer. Maybe you might just comment on how quickly you can use PSA in studies after people were exposed to both agents.

喬治，有個關於前列腺癌生物標記的問題。您能否談談在患者同時接受兩種藥物治療後，PSA 在研究中的應用速度如何？

Right. And some of the data we've already shown and we will continue to show many of our patients have remarkably high PSA levels because they have very high burden of disease, as we all know, depending on the assay and the labs and so forth, normal PSA levels are in the single to low-single digits, maybe 1 to 4 is considered the highest levels. We have patients who entered into our study with PSAs in the hundreds, 500, 600 and so forth. And we saw with this combination treatment as soon as you put the combination on board, essentially at the next time point that we measured within 3 weeks or so, we saw a dramatic drop on the order of 99% reductions in the PSA. And these are really astounding results. And now where we continue to follow up patients over time. We've seen that, for example, bone lesions have entirely normalized and so forth. So the effects are incredibly rapid as reflected in the PSA.

沒錯。我們已經展示過一些數據，並且會繼續展示，很多患者的PSA水平都非常高，因為他們的疾病負擔很重。眾所周知，根據檢測方法和實驗室的不同，正常的PSA水平在個位數或低個位數，最高值可能在1到4之間。在我們研究的患者中，有些PSA值高達數百、500、600甚至更高。我們發現，採用這種聯合治療後，一旦開始合併治療，大約在3週後的下一次測量中，PSA值就出現了顯著下降，降幅高達99%。這些結果確實令人震驚。現在，我們繼續對患者進行長期追蹤。我們發現，例如，骨骼病變已經完全恢復正常等等。因此，從PSA值的變化來看，療效非常迅速。

And to the point about predicting which patients respond, it doesn't matter whether you had patients who had relatively low burden as measured by PSA, where their PSA was measured in the in, let's say, 40 to 50 range or whether you had incredibly high PSAs in the 500 to 600 range, those patients seem to similarly respond in terms of very dramatic very profound drops in the PSA within weeks of starting therapy.

至於預測哪些患者有反應這一點，無論患者的 PSA 值相對較低（例如在 40 到 50 之間），還是 PSA 值非常高（例如在 500 到 600 之間），這些患者在開始治療後的幾週內，PSA 值似乎都會出現非常顯著的下降，反應也類似。

And as we've continued to follow these patients, incredibly durable responses are first patient has now been out for more than a year. Their immune side effects have resolved, whereas their complete remission has remained completely intact. And as I said, not only completely normalize the PSA levels, but the bone lesions and so forth have all normalized, at least as measured by bone scans and so forth. So this is really -- has the potential to be so game-changing for these late-stage patients who really have at this point, no other real recourse.

隨著我們對這些患者的持續追踪，我們發現療效極其持久。首例患者出院已超過一年。他們的免疫副作用已經消退，完全緩解狀態也保持完好。正如我所說，不僅PSA水平完全恢復正常，骨骼病變等也全部恢復正常，至少從骨骼掃描等檢查結果來看是如此。因此，對於那些目前別無他法的晚期患者而言，這確實有可能帶來翻天覆地的改變。

Thank you, Len, George. I think we have time for one more question, Towanda.

謝謝，倫，喬治。托萬達，我想我們還有時間再問一個問題。

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

最後一個問題來自卡特·古爾德在巴克萊銀行的業績。

Maybe just to come back to -- for Marion, just how we should think about your expectations for the time line to receive a J-code for high-dose EYLEA next year. We've seen in the past pretty varied time lines here in terms of Libtayo there has turned around almost immediately Roche clearly had a more paced process. And I guess more to the point, should our expectation be that's more of like a January 1, 2024 type event? Or is the potential for a J-code maybe in the later part of '23?

也許我們還是回到正題——對於Marion來說，我們應該如何看待你對明年獲得高劑量EYLEA的J代碼的預期？過去我們看到Libtayo的審批時間差異很大，有的幾乎立即就獲得了批准，而羅氏的審批流程顯然更為謹慎。我想更確切地說，我們應該預期EYLEA會在2024年1月1日左右獲得批准嗎？還是說J代碼有可能在2023年下半年取得？

Thank you for the question. And certainly, we'll stay very close on this. And obviously, the importance of new BLA, new J-code is important. In terms of timing, I would need a crystal ball. Certainly, we'd share with you. We'll be working very closely with the proper organizations and officials. But at this time, it's too early to give anything definitive on expectation for J-code timing.

感謝您的提問。當然，我們會密切關注此事。顯然，新的BLA和新的J程式碼非常重要。至於具體時間，我恐怕無法預知。當然，我們會與您分享相關資訊。我們將與相關機構和官員緊密合作。但目前，對於J代碼的發佈時間給出任何確切的預期還為時過早。

Yes. And this in Len, I mean my own perspective, I'm just slightly different is that I'm not convinced in this particular setting that the J-code is like the end of deal of -- like you're going to see these dramatic changes in uptakes post J-code.

是的。至於Len，我的意思是，就我個人而言，我的看法略有不同，我並不認為在這種特定情況下，J代碼就意味著一切的終結——就像你會看到J代碼出現後，用戶數量會發生劇烈的變化一樣。

Okay. I think that's all we have time for today. Thank you, everyone, for joining the call. As always, the Investor Relation is standing by for any follow-up questions you may have. Have a great day, everyone.

好的。我想今天就到這裡吧。感謝各位參加本次電話會議。投資者關係部門隨時準備好解答您可能提出的任何後續問題。祝大家今天愉快。

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect

女士們、先生們，今天的電話會議到此結束。感謝各位的參與。現在您可以掛斷電話了。