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，歡迎來到 Regeneron Pharmaceuticals 2022 年第三季度收益電話會議。我叫托旺達；我將成為您今天通話的接線員。 （操作員說明）請注意，本次會議正在錄製中。

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

我現在想將電話轉給投資者關係副總裁 Ryan Crowe。你可以開始了。

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.

謝謝你，托旺達。早上好，下午好，晚上好，全世界的每一個人都在聽。感謝您對 Regeneron 的興趣，並歡迎參加我們的 2022 年第三季度收益電話會議。電話會議結束後不久，我們的投資者關係網站將提供此網絡廣播的存檔。今天加入我的是創始人、總裁兼首席執行官 Leonard Schleifer 博士； George Yancopoulos 博士，聯合創始人、總裁兼首席科學官； Marion McCourt，執行副總裁兼商務主管；和執行副總裁兼首席財務官 Bob Landry。在我們準備好發言後，我們將打開問答電話。

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.

我還想提醒您，今天在這次電話會議上發表的言論包括 Regeneron 的前瞻性陳述。此類聲明可能包括但不限於與再生元及其產品和業務、財務預測和指導、開發計劃和相關預期里程碑、合作、財務、監管事項、付款人覆蓋範圍和報銷問題、知識產權、待定訴訟和其他訴訟和競爭。

Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-Q for the quarterly period ended September 30, 2022, which was filed with the SEC this morning.

每項前瞻性陳述都存在風險和不確定性，可能導致實際結果和事件與該陳述中的預測存在重大差異。有關這些和其他重大風險的更完整描述，請參見 Regeneron 向美國證券交易委員會提交的文件，包括今天上午向 SEC 提交的截至 2022 年 9 月 30 日的季度的 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. 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.

Regeneron 不承擔任何義務更新任何前瞻性陳述，無論是由於新信息、未來事件或其他原因。此外，請注意，GAAP 和非 GAAP 措施將在今天的電話會議中討論。有關我們使用非 GAAP 財務指標的信息以及這些指標與 GAAP 的對賬信息，請參閱我們的財務業績新聞稿，該新聞稿可在我們的網站上訪問。一旦我們的通話結束，Bob Landry 和 IR 團隊將可以回答更多問題。

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

有了這個，讓我把電話轉給我們的總裁兼首席執行官 Len Schleifer 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.

謝謝你，Ryan，也謝謝大家加入今天的電話會議。 Regeneron 強勁的運營勢頭在第三季度繼續保持，突出體現在我們管道的重要發展和出色的商業執行。剔除我們的 COVID 抗體雞尾酒的貢獻時，本季度總收入比去年增長 11% 隨著 Dupixent 和 Libtayo 的全球淨銷售額以及 EYLEA 的美國淨銷售額再次達到歷史新高並增長兩位數。

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.

在深入研究我們的商業結果之前，我想回顧一下我們在管道中取得的一些最新進展，首先是我們在 9 月報告的用於調查阿柏西普 8 毫克的驚人關鍵數據，我們相信這些數據最終可能改變患者的治療環境。由於近 90% 的 DME 患者和 80% 的濕性 AMD 患者能夠在 48 週的治療中維持 16 週的維持劑量，我們相信阿柏西普 8 毫克可能會改變當前的治療模式，讓更多的患者接受更少的注射頻率，同時實現視力提高、解剖學上的改進和與 EYLEA 相媲美的安全性。事實證明，要減少超過十年前我們使用 EYLEA 所能達到的治療負擔是非常困難的，因為許多潛在的治療由於視覺效果欠佳或安全問題而失敗。

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.

最近批准的一種抗 VEGF 藥物在關鍵研究中沒有證明大多數患有這兩種疾病的患者能夠在整個治療的第一年維持 16 週的維持劑量，這支持了我們的觀點，即阿柏西普 8 毫克有可能成為假設監管部門批准，下一代護理抗 VEGF 治療標準。我們計劃在今年年底根據單一 BLA 向 FDA 提交 aflibercep 8 毫克的關鍵數據，並決定使用先前授予的優先審查憑證來加快 FDA 審查過程。 FDA 可能會在 2023 年 8 月下旬批准上市前的計劃。

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.

除了關鍵的 aflibercep 8 毫克數據外，再生元在我們的免疫學和腫瘤學管道上繼續取得顯著進展。從免疫學開始。 9 月，我們獲得 FDA 批准 Dupixent 治療結節性癢疹，這是該適應症的第一個全身治療，也是 Dupixent 現在獲批的第五種疾病。

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，將符合治療條件的人群擴大了約 225,000 名患者，其中包括 2 種以前沒有獲得 FDA 批准的全身療法的疾病。

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，我們期待歐盟對 6 個月以下患者的嗜酸性食管炎、結節性癢疹和特應性皮炎的監管決定。有了這些潛在的額外適應症，大約 200,000 多名患有這些 2 型炎症性疾病的患者可以從 Dupixent 無與倫比的臨床特徵中受益。此外，我們預計明年上半年 Dupixent 在慢性可誘發寒冷性蕁麻疹和慢性阻塞性肺病中的關鍵數據讀數。

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.

轉向腫瘤學，我們管道的深度和廣度使 Regeneron 最終成為全球領導者。我們在今年的歐洲醫學腫瘤學會年會上展示了幾個數據集，進一步強調了 Libtayo 作為我們整體腫瘤學戰略基礎的重要性。 George 將在他的講話中更詳細地審查數據，但我們對 Libtayo 單藥治療新輔助 CSCC 的結果以及 Libtayo 與 Fianlimab 聯合治療的結果感到特別鼓舞，Fianlimab 是我們在一線轉移性黑色素瘤中的 LAG-3抗體。我們還展示了我們的 MUC16xCD3 雙特異性治療復發性卵巢癌的單藥治療數據，該數據有可能與 Libtayo 結合使用，以及我們的 METxMET 雙特異性雙特異性治療金屬非小細胞肺癌的數據。我還注意到我們的 PSMA 通過 CD28 共刺激雙特異性與 Libtayo 組合的早期但非常令人興奮的結果，這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.

參加我們研究的患者預後較差，預期生存期為 1 至 2 年，具體取決於他們的治療史。鑑於前列腺癌在很大程度上對 PD-1 抑制和免疫療法沒有反應，顯然需要新的治療方法。僅在 2020 年，全球就有超過 375,000 人死於前列腺癌，它是美國男性癌症死亡的第二大原因。自從我們在 8 月份報告了我們的頂級結果以來，我們繼續擴大我們在前列腺癌方面的共刺激雙特異性研究，並加快了我們首次人體研究的註冊人數，我們期待在上半年向您更新該計劃明年的。

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.

現在轉向我們的商業表現。第三季度，EYLEA 全球淨銷售額按固定匯率計算增長 8% 至 24 億美元。在美國， EYLEA 的淨銷售額為 16.3 億美元，同比增長 11%，超過了僅 4% 的抗 VEGF 類別增長。儘管最近有品牌和生物仿製藥進入，但 EYLEA 在美國的抗 VEGF 類別份額創下了歷史新高。

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.

Dupixent 繼續以驚人的速度增長，這得益於先前批准的適應症中新疾病和年輕患者群體的批准。第三季度，全球淨產品銷售額為 23 億美元，按固定匯率計算比去年增長 45%，反映了所有地區所有跡象的增長。 Dupixent 的差異化臨床特徵和有效治療越來越多患者的能力，包括目前批准的適應症和潛在的其他 2 型炎症性疾病——預計將推動未來的強勁增長。

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.

Libtayo 第三季度全球總淨銷售額增長 25% 至 1.43 億美元，其中包括非黑色素瘤皮膚癌適應症和單藥治療非小細胞肺癌推動的美國增長 21%。在第三季度初，我們從賽諾菲（Sanofi）獲得了 Libtayo 的全球權利，未來的潛在組合包括非小細胞肺癌的化療以及其他正在開發的管道藥物，我們相信 Libtayo 有望成為更有意義的公司一段時間內的收入貢獻者。

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.

我們對我們核心產品的強勁商業表現、我們報告的 aflibercep 8 毫克令人信服的功效、安全性和耐用性數據以及我們在推進我們的管道，特別是在腫瘤學方面取得的顯著進展感到興奮。我們的產品線現在包括大約 35 個處於臨床開發階段的候選產品，其中包括一些我們正在調查其他適應症的上市產品，George 稍後將討論其中一些產品。

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，我們的戰略繼續專注於投資我們的內部研發能力，同時探索使我們能夠充分發揮科學力量的潛在合作。我們對這一戰略和我們的增長前景以及我們為患者帶來突破和為股東創造價值的能力仍然充滿信心。

Now I'll turn the call over to George.

現在我將把電話轉給喬治。

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.

謝謝你，萊恩。我將從眼科開始。在 PULSAR 和 PHOTON 研究中，阿柏西普 8 毫克的積極關鍵結果，我們最近在美國眼科學會年會上提出。這些濕性 AMD 和 DME 試驗的結果分別表明，非常高比例的患者能夠以 12 周和 16 週的給藥間隔快速啟動並成功維持至第 48 週。在實現不低於當前護理標準的視力增益的同時，EYLEA 每 8 週服用 2 毫克劑量。這些結果表明，阿柏西普 8 毫克有可能成為這些視網膜疾病的新護理標準。我認為如果我們後退一分鐘並嘗試將這些結果放在上下文中會很有幫助。

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.

雖然我們的試驗所做的只是突破了目前任何可用的抗 VEGF 療法所能達到的極限。我們的試驗不是使用反應標準來嘗試識別或緩慢延長患者的給藥間隔，而是測試是否所有患者都可以隨機分配并快速開始延長阿柏西普 8 毫克的給藥間隔，而不會影響視力改善或安全性。這些阿柏西普 8 毫克試驗為絕大多數人完成了這一目標，同時提供了與 EYLEA 一致的安全性。 89% 的 DME 患者和 77% 的濕性 AMD 患者——我們能夠快速啟動並維持 16 週的阿柏西普 8 毫克給藥方案，而 93% 的 DME 和 83% 的濕性 AMD 患者我們'能夠在至少 12 週的給藥間隔內快速啟動，同時提供與每 8 週給藥一次的 EYLEA 相似的功效。

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.

我們相信這些確實是前所未有的並且可能改變遊戲規則的結果，這是使用任何其他抗 VEGF 藥物都沒有實現的。這推測我們的 PDUFA 和 PHOTON 結果是由於我們的劑量修改標準，甚至試圖從理論上推斷他們的代理可能以某種方式使用我們的標準接近這些結果。我們將這些推測性的推斷歸入一廂情願的範疇。根據我們對數據的專家分析，我們得出結論，這完全與藥物有關，而不是試驗設計。

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.

簡要介紹 Dupixent。在我們最近批准的成人和青少年嗜酸性食管炎的基礎上，我們計劃在 2023 年中期提交一份針對嗜酸性食管炎和 1 至 11 歲兒童的補充 BLA。 Dupixent 治療嗜酸性粒細胞性食管炎的能力凸顯了我們的 IL-4 和 IL-13 阻滯劑更完全針對整個 2 型炎症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.

正如你聽到 Len 提到的，FDA 標籤在第三季度再次擴大，因為 Dupixent 成為第一個也是唯一一個治療結節性癢疹（一種使人衰弱的慢性皮膚病）的藥物。這標誌著 Dupixent 現在被批准用於治療的第五種疾病。我們與 Dupixent 的集體臨床數據支持這些相關疾病的統一分子機制，從哮喘到特應性皮炎到鼻息肉到結節性癢疹到嗜酸性食管炎。在這個統一的假設中，IL-4 和 IL-13 誘導的炎症正在驅動不同組織區室中的所有這些相關疾病。

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.

搬到 Libtayo 從事腫瘤學。在第三季度，我們強大的腫瘤學管道已開始提供來自我們最新和最具創新性的項目的數據讀數，我們預計這些讀數將在 2022 年剩餘時間內加速並持續到 2023 年。歐洲醫學腫瘤學會或 ESMO ，9 月的年會，對於 Regeneron 來說確實是一次標誌性的活動，有幾個值得注意的關於我們腫瘤學管道資產的口頭報告，我想簡要總結一下。

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.

從 Fianlimab 開始，我們的 LAG-3 抗體與 Libtayo 相結合。在 ESMO，我們共享了來自我們首次人體研究的 2 個獨立的晚期黑色素瘤擴增隊列的數據，重要的是顯示了 2 個重複隊列之間的一致療效和安全性。 Fianlimab 與 Libtayo 聯合在每個隊列中顯示出超過 60% 的反應率，兩個隊列的中位 PFS 估計為 24 個月，中位反應持續時間尚未達到。該組合的初步安全性似乎與抗 PD-1 單一療法一致，並且與抗 CTLA-4 組合相比可能具有更低的毒性。

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.

雖然雙重 LAG-3 和 PD-1 抑制先前已在晚期黑色素瘤中顯示出前景，但之前沒有報導過超過 45% 的中位 PFS 超過 1 年的反應率。這些黑色素瘤的初步結果表明，Fianlimab-Libtayo 組合在這種情況下具有潛在的同類最佳特徵。我們正在招募我們的 III 期轉移性黑色素瘤研究——我們打算在今年晚些時候啟動一項 III 期輔助黑色素瘤研究，並在 Fianlimab 有可能成為一流的其他實體瘤中製定額外的計劃。

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.

Libtayo 單一療法的 II 期研究新輔助皮膚鱗狀細胞癌或 CSCC 已顯示出有希望的結果。在對大腫瘤患者進行潛在治愈性手術之前給予 Libtayo 能夠在手術前為 63% 的患者提供主要的病理反應。這增加了 Libtayo 可以為每年需要這些手術的許多患者減輕這些重大且可能毀容手術的負擔的可能性。我們很高興在 ESMO 報告的同時，這些數據發表在《新英格蘭醫學雜誌》上。

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.

關於下一步，我們正在與監管機構討論可能的標籤途徑和可能納入 NCCN 指南的途徑。同樣在 ESMO，我們展示了 Ubamatamab 和我們為晚期卵巢癌開發的 MUC16xCD3 雙特異性的初步臨床數據，這是我們在實體瘤中的第一個 CD3 雙特異性臨床數據。在經過大量預處理的卵巢癌人群中，我們觀察到在腫瘤過度表達 MUC16 的患者亞群中對這種 MUC16xCD3 單一療法的持久反應，反應率高達 31%。大多數 Vergent 不良事件的治療發生在初始遞增劑量。 Ubamatamab 正在開發為單一療法以及與 Libtayo 組合以及與我們的 MUC16 costim 雙特異性組合。我們期待 2023 年在這些計劃中獲得更多數據。

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.

在我們的 ESMO 投資者介紹中，我們分享了 CD28 costim 雙特異性的 PSMA 的更詳細數據，並與 Libtayo 相結合，代表了這種新型雙特異性藥物的首個療效和安全性數據，我們最初在第二季度收益中對其進行了討論和討論。此後，我們繼續在這項研究中招募患者，併計劃在 2023 年上半年的醫學會議上提供更新的數據。

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 hem/onc 管道，我們期待來自 odronextamab 的數據。 -- 我們的 CD20 x CD3 雙特異性以及 linvoseltamab，我們的 BCMA by CD3 雙特異性在 12 月的美國血液學會或 ASH 年會上。對於 odronextamab，我們將在 2 個單獨的口頭報告中展示濾泡性淋巴瘤和瀰漫性大 B 細胞淋巴瘤的關鍵 II 期數據。在與 FDA 討論後，我們現在的目標是在 2020 年下半年為該項目提交監管文件。我們希望在不久的將來啟動與適當的 CD20 costim 雙特異性聯合研究。

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雙特異性抗體仍在開發中，併計劃在 2023 年與 FDA 進行討論。我們現在已經完成了我們潛在的關鍵 II 期研究的註冊。正如我之前提到的，這項研究的數據將在 ASH 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 與共刺激雙特異性藥物的聯合研究。我們相信，現有的護理治療標準為這些難以治療的環境留下了很大的改進空間，我們對迄今為止為 odronextamab 和 linvoseltamab 生成的中期療效和安全性數據感到鼓舞。

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，我們還分享了 METxMET 雙特異性抗體在 MET 改變的非小細胞肺癌中的初步數據。具有較高水平表達的患者的反應豐富。未觀察到劑量限制性毒性。即使 MET 的適度過度表達也可能使肺癌易受這種作用機制的影響，我們期待明年的 METxMET 抗體藥物偶聯物數據。

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.

總結腫瘤學，管道的豐富評論員正在提供有競爭力的數據。憑藉我們對 Libtayo 的全部所有權，我們對通過我們的投資組合方法推進腫瘤護理標準的潛力感到興奮。

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.

以 Regeneron 基因藥物的努力結束，我們將繼續推進我們的管道和發現引擎。 9 月，我們和 Alnyam 報告了我們正在進行的 Alnylam HSD 在非酒精性脂肪性肝炎或 NASH 中的 I 期研究的有希望的數據。 --我們計劃很快啟動一項 II 期研究，這只是我們多管齊下的方法的一部分，探索 NASH 的多個基因驗證目標。

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 公佈了我們正在進行的 NTLA-2001 I 期研究的心肌病部門的初步數據，NTLA-2001 是一種基於 CRISPR 的研究性療法，用於治療轉甲狀腺素蛋白澱粉樣變性，顯示深度和持續的平均血清 TTR 降低超過 90 % 並且通常耐受性良好。最後，在 10 月，我們的合作者 a decibel Therapeutics 宣布 FDA 批准 DB-OTO 的 NDA 申請，這是我們第一個病毒交付的基因治療產品候選者，旨在為患有 otoferlin 相關聽力損失的個體提供聽力。該 IND 提供了在美國啟動兒科 I/II 期臨床試驗的許可。

With that, I will turn it over to Marion.

有了這個，我會把它交給馬里恩。

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.

謝謝你，喬治。我們第三季度的業績反映了我們商業投資組合的強勁增長。我們繼續擴大我們在其他治療類別的領導地位，這是我們為有需要的患者提供改變生活的藥物承諾的一部分。隨著 Dupixent 在結節性癢疹中的批准，Libtayo 與化療聯合用於一線晚期非小細胞肺癌的預期批准以及最近的數據表明 aflibercept 8 毫克 Regeneron 的商業業務令人信服，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,

從第三季度全球淨銷售額達到 24 億美元的 EYLEA 開始。這意味著按固定匯率計算增長了 8%，對於一個 11 年前推出的品牌來說，這是一項了不起的成就。在美國， EYLEA 淨銷售額同比增長 11% 至 16.3 億美元，本季度再次實現超過 100 萬次注射。儘管從 2022 年第二季度到第三季度整體品類銷量環比下降 2%，

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 在所有適應症上繼續增長，從品牌和非品牌代理商那裡獲得了份額。事實上，EYLEA 的品類份額達到了歷史最高水平，約為 50%，在品牌品類中佔據了 75% 的份額。我們繼續加強和擴大 EYLEA 在抗 VEGF 類別中的領導地位。

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 的兒科獨占權，從而將 EYLEA 美國市場的獨占期再延長 6 個月，直至 2024 年 5 月 17 日。自今年早些時候宣布積極的 III 期結果以來，人們普遍感到興奮視網膜社區關於阿柏西普 8 毫克數據集和阿柏西普 8 毫克在獲得批准後成為未來護理標準的潛力。

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.

在利塔約旁邊。全球產品總銷售額為 1.43 億美元，按固定匯率計算增長 25%。在美國，基於我們的肺部和非黑色素瘤皮膚適應症的增長，淨銷售額增長了 21% 至 9500 萬美元。隨著時間的推移，我們看到了肺癌增長的特殊機會。在單一療法中，開藥者和總利用率已經穩步增加。我們已準備好接受潛在的化療組合批准，這顯著擴大了患者的機會。

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，對於 Dupixent，第三季度全球淨銷售額為 23 億美元，按固定匯率計算增長 45%。在美國，由於對特應性皮炎、哮喘和鼻息肉的強勁需求，淨銷售額增長了 45% 至 18.2 億美元。最近適應症的快速啟動軌跡也推動了增長，包括嗜酸性食管炎和小兒特應性皮炎，其中 Dupixent 是唯一從嬰儿期到成年期獲得批准的生物製劑。從皮膚病學和特應性皮炎開始， Dupixent 是領先的一線全身治療藥物，在中度至重度疾病譜和年齡組中具有強大的吸收能力。正在進行的針對 6 個月大的兒童的推出進展順利，為兒童及其家人提供了緩解，並加強了 Dupixent 對所有年齡組的安全性。在獲得批准治療結節性癢疹後，我們還擴大了 Dupixent 在皮膚病學領域的領導地位。 Dupixent 是唯一獲得 FDA 批准的治療這種慢性衰弱性皮膚病的藥物，這種疾病影響了美國大約 75,000 名成年人。早期推出指標是積極的，患者已經開始接受治療。

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.

Dupixent 在競爭激烈的哮喘市場上也繼續表現良好，處方和新患者開始以及鼻息肉的穩定增長。嗜酸性食管炎的早期上市表現非常強勁，被胃腸病學家和過敏症學家廣泛採用。醫學界已經接受了 Dupixent，因為患者以前的選擇非常有限 Dupixent 是唯一用於治療嗜酸性食管炎的藥物，也是唯一被證明可以解決潛在疾病原因的治療方法，從而導致前所未有的症狀緩解。在美國，大約有 50,000 名成人青少年患者，我們將繼續推進我們在年輕患者中的臨床工作，這些患者仍有大量未滿足的需求。美國以外的 Dupixent 淨銷售額為 5.06 億美元，按固定匯率計算增長 44%。批准的適應症迅速被採用，我們繼續執行最近的發布並擴展到新的地區。作為其中的一部分，再生元在主要國際市場的影響力增加，支持將 Dupixent 帶給更多患者的努力。

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，我們第三季度的業績證明了我們商業投資組合的實力和增長。我們正在成功地執行為患者提供改變生活的藥物的計劃，並推進戰略以最大限度地提高新的和即將推出的產品。我們的商業組合定位良好，可以推動長期和可持續的增長。

Now I'll turn the call to Bob.

現在我將把電話轉給 Bob。

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.

謝謝你，馬里恩。除非另有說明，否則我今天對 Regeneron 的財務業績和前景的評論將基於非公認會計原則。 Regeneron 在第三季度表現良好，主要品牌的增長和整個業務的執行，繼續推動收入和利潤的強勁財務業績。不包括與 COVID-19抗體雞尾酒相關的全球收入，第三季度總收入同比增長 11% 至 29 億美元，表明我們核心業務的持續增長勢頭反映了 Libtayo 交易的有利影響。

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.

第三季度每股攤薄淨收益總額為 11.14 美元，淨收益為 13 億美元。從合作收入開始，從拜耳開始。 2022 年第三季度（不包括美國 EYLEA）的淨產品銷售額為 8.17 億美元，按固定匯率計算，比 2021 年第三季度增長 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的 EYLEA 淨利潤中所佔份額有關。在 Dupixent 的推動下，賽諾菲在 2022 年第三季度的合作收入為 7.11 億美元，同比增長 22%。

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.

回想一下，在 Libtayo 交易中，我們將抗體合作開發餘額的償還額從抗體合作利潤的 10% 增加到 20%，其中一部分被記錄為抗體合作收入的減少，而另一部分被記錄為抗體合作收入的減少。記為研發費用。鑑於 Regeneron 現在記錄了其在抗體合作研發費用中的全部 50% 份額。此前，Regeneron 僅在發生時確認其抗體合作研發費用的部分份額，剩餘的費用份額被添加到抗體開發餘額中。

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，正如我們在上個季度強調的那樣，根據協議，我們記錄了 5700 萬美元的一次性開發餘額償還，作為 2022 年第三季度賽諾菲合作收入的增量減少。我們已在我們的網站上發布支持材料以進一步解釋與 Libtayo 交易的這一要素和其他要素相關的會計。

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.

現在轉到我們的運營費用。研發同比增長 38% 至 8.17 億美元，部分原因是 Libtayo 交易的影響，該交易以兩種方式影響研發。首先，Regeneron 現在記錄了 Libtayo 的所有研發費用，這些費用以前與賽諾菲平分。其次，正如我之前提到的，Regeneron 現在記錄了我們在 Dupixent 和 itepekimab 的抗體合作支出中的全部 50% 份額。

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.

SG&A 費用同比增長 20% 至 4.67 億美元，主要是由於與承擔 Libtayo 全球權利相關的成本增加。第三季度的商品銷售成本為 1.09 億美元，該季度的產品毛利率增長了 94%，而去年同期為 90.2%。更有利的毛利率是由於本期間 REGEN-COV 銷售的非經常性在取消向賽諾菲支付其在美國 Libtayo 毛利率中的份額而推動的。最後，2022 年第三季度的有效稅率為 12.1%，而去年為 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.

現在轉向現金流和資產負債表。 2022 年年初至今，Regeneron 已產生 29 億美元的自由現金流，截至 2022 年第三季度，現金和有價證券減去債務約為 103 億美元。我們仍然專注於利用我們強大的財務狀況為股東創造長期價值。在 2022 年的前 9 個月，我們部署了超過 28 億美元的資本。我們已經執行了大約 12 億美元的業務發展計劃，包括以 9 億美元收購 Libtayo 權利。此外，我們已經回購了超過 16 億美元的股票，其中僅在第三季度就回購了超過 9 億美元。截至 9 月 30 日，我們目前的股票回購授權剩餘約 12 億美元，我們仍然是機會主義買家。

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.

隨著我們接近年底，我們對 2022 年的指導範圍進行了一些小改動。我們今天上午早些時候發布的新聞稿中提供了我們最新的全年財務指導的完整摘要。

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.

除了這些變化之外，我還想就我們 2023 年的費用前景提供一些初步想法。我們繼續進行投資以推進我們的管道並為公司的長期增長做好準備。我們預計 2023 年研發投資的增長將與今天早些時候報告的 9 個月的年初至今增長率相當或略高。 2023年的增量研發投資將由推進我們的免疫腫瘤學、血液學、免疫學和基因醫學管道以及我們研發組織的持續擴張來推動。

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 交易影響的第一個全年，在該交易中，我們記錄了 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的全部 50% 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.

對於 2023 年的 SG&A，我們目前預計與 2022 年相比增長在十幾歲左右，因為我們將記錄一整年的全球 Libtayo 費用，以及對我們國際基礎設施建設的有針對性的投資。

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，對於 2022 年第三季度的其他營業收入和費用，我們確認了剩餘的 4400 萬美元遞延收入，這些遞延收入與之前收到的 Fasinumab 預付款和因該計劃終止而導致的開發里程碑相關。在沒有任何新交易的情況下，我們目前預計 2022 年第四季度及 2023 年及以後不會有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.

總之，再生元在 2022 年前 9 個月的表現異常出色，我們強大的財務狀況使持續投資能夠推動長期增長。

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

這樣，我會將電話轉回給 Ryan。

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.

謝謝你，鮑勃。 Towanda，我們準備好的發言到此結束。我們現在想打開隊列中的呼叫者數量的問答電話，我想確保我們能夠解決盡可能多的問題。因此，我們只能回答每個來電者的一個問題，然後再轉到下一個問題。 Towanda，請打開問答電話。

(Operator Instructions)

（操作員說明）

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?

祝賀進展。因此，資產負債表上有近 130 億美元，債務極少。您能否為您的資本配置優先事項提供更多色彩？您會考慮更大規模的業務發展並派發股息嗎？

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.

是鮑勃。關於資本配置，今天我們在研發方面的增長和 2023 年的前瞻性指引證明了這一點，我們將繼續投資，首先是我們今天上午發布 10-Q 的研發管道。在 MD&A 中，您會看到目前正在進行的大量試驗。正如喬治在他的劇本中提到的那樣，我們非常看好正在籌備中的內容。再說一次，關於業務發展，這不是結束或或，對嗎？正如您所看到的以及我們在 2022 年的前 9 個月所做的工作，我們確實認為有機會並且我們確實認為我們可以在 1 加 1 等於 3 的情況下進行合作，那麼我們絕對會抓住這個機會.

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 Checkmate 就是一個很好的例子。我希望你會看到更多。關於你關於股息的問題，從來都不是。顯然，該工具在我們的工具箱中。如果我們決定現在就打出那張牌，那麼在可預見的未來，我們的計劃不會有紅利。我們在回購方面非常投機取巧。同樣，今天早些時候發布的 MD&A。 10-Q 將向您展示我們一直在回購我們的股票。同樣，我們仍將是機會主義買家，根據我們目前的 30 億美元授權，我們確實還有剩餘的 12 億美元。

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

我們的下一個問題來自 Tyler Van Buren 和 Cowen。

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.

祝賀偉大的季度。所以我剛剛提取了 odronextamab 和 5458 ASH 摘要。很高興能從你們那裡得到一個簡短的預覽以及你需要什麼——你認為你最終需要在會議上展示的東西才能與其他人展示的東西相比具有競爭力。

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，鑑於會議很快就要召開了，我認為我們不想自卑。但 odronextamab 有可能成為一個非常重要的分子。我們認識到，我們前面還有一些人。我們認識到，根據最近的監管反饋，最近的一些時間線已經推遲了一點。監管機構最近一直專注於在提交申請時大量註冊 III 期試驗，然後再給予加速批准。但我們對 odronextamab 的概況充滿信心，正如 George 所說，未來還有可能與我們管道中的其他東西組合，甚至可以真正引領我們。

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 Salveen Richter。

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

在 EYLEA 上，您對自己和羅氏之間的業務啟動市場有何觀察？

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.

很高興能給出更多的描述。正如我所提到的，我們看到 EYLEA 繼續表現出色，達到歷史最高水平，類別份額達到 50%，現在我們與包括羅氏 (Roche) 在內的其他品牌代理商一起參與的整個品牌市場也在增長。我要提到的一件事是，為了更深入地了解，EYLEA 獲得了主要來自 Lucentis 和 Avastin 的增長。事實上，如果將羅氏的產品組合放在一起，EYLEA 的增長顯然是積極的，而羅氏產品的整體市場份額則有所下降。

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，我想知道您是否可以評論一下您對 Dupixent 的 COPD 研究的前景以及您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，對於新療法和生物製劑而言，COPD 一直是一種非常困難的疾病，特別是，我們認為有一類 COPD 患者患有或具有更多我們稱之為 Th2 型炎症的特徵，我們認為，正如我在我的話，有一個統一的假設，即有很多 TH2 類型的疾病以不同的方式表現出來。我們認為，這部分 COPD 患者可能、可能或適合該類別，並且能夠使這些患者受益。

(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.

（技術難度）減少病情惡化和/或改善肺功能的術語確實會對這些患者產生影響。因此，我們正在焦急地等待數據，我們希望我們將有另一組患者，我們可能能夠證明 Dupixent 確實可以發揮作用。

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

我們的下一個問題來自沃爾夫研究公司的蒂姆安德森。

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.

禮來公司將在 23 年推出 lebrikizumab 在特應性皮膚中，他們的數據看起來可以與 Dupixent 相媲美，至少在這一跡像上，儘管在機制上並不相同，但幾乎是直接競爭對手。由於 Taltz，他們知道真皮空間，並且定位將是他們可以每月服用一次，而 Dupixent 每兩週服用一次。所以我想知道您是否對該產品有任何強烈的看法，或者您是否認為這將是一個完全非首發，這幾乎是共識觀點。

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.

也許 Marion 可以對此發表評論。但是看，這個市場上還有競爭對手的空間。我們真的很謙虛地抓住了這個機會。我認為你所說的內容實際上不會像我們迄今為止所看到的那樣，它們與我們最早從嬰儿期到成年期的相似。這是一件大事，好嗎？此外，事實上，這些人中的許多人都有其他合併症，例如哮喘或鼻息肉，而且他們可以得到——如果他們確實有合併症，單一藥物可以治療這兩者是一個很大的區別，所以我想想當你是市場領導者，當你遙遙領先，當你真正擁有差異化形象時，你就有優勢。顯然，禮來是一家不錯的公司。他們知道自己在做什麼。但正如我所說，當新的好藥上市時，經常有空間，市場有增長。我們不會追踪固定數量的患者。我們實際上正在培養這些患者。 Marion，我不知道你是否想補充什麼。

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.

我只想補充一點，我們與之交談的大多數關鍵意見領袖都認識到雙重作用機制，即抗 IL-4 和抗 IL-13 非常非常重要。所以當然，不應該假設功效。對於患有中度真正重度疾病的患者來說，這種令人難以置信的療效也得到了加強。顯然，現實世界的經驗令人信服，使用 Dupixent 的管理非常簡單。它是自我管理，我們實際上看到積極的患者或父母的參與對建立 Dupixent 非常有幫助，但當然，正如 Len 所提到的，擴大教育和類別以將更多的特應性皮炎患者納入治療連續體對患者來說是非常積極的當然對於 Dupixent。

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.

不是為了堆砌，而是因為——只是為了補充萊恩所說的話。我的意思是，IL-13 在這些其他重要的 TH2 炎症驅動的疾病（如哮喘、COPD 和其他疾病）中失敗的事實確實表明它們並沒有完全解決任何一種特定疾病中的 TH2 炎症，而且，正如 Len 所說，這些人中的許多人，如果你只看我們的標籤或任何描述這些疾病的標籤，他們就會患有其他過敏性合併症。顯然，您可以為患者帶來如此不同的效果，一種藥物可以治療全身性疾病，而不是僅在疾病表現出來的眾多隔間之一中治療疾病。我認為這就是我認為該領域的醫學應該發展的方式。這是一種全身性疾病，其中 TH2 炎症可能在身體的許多隔間中加劇，您不僅想在一個隔間內治療，還想治療整個身體。這就是我們通過使用 Dupixent 治療一種又一種疾病來系統地展示的內容。它在每個隔間都起作用，並且廣泛地攻擊與所有這些疾病相關和致病的潛在炎症。

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.

祝賀進展。如果我可以進一步探討你對抗 VEGF 市場增長的評論，你說它同比增長約 4%，與我們所看到的高增長相比似乎有點放緩。您能否進一步詳細說明，您是否只看到四分之一。你在那裡看到任何潛在的趨勢嗎？是因為我們在 COVID 之後看到的高速增長正在逐漸減少嗎？如果你能幫助我們理解這一點。

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.

我認為很難推斷出四分之一。當然，我確實提到過從第二季度到第三季度整體抗 VEGF 類別連續下降了約 2%，但我認為很難從中推斷出來。你分享的類別整體同比增長約為 4% 的數字，我們也認識到，我認為隨著時間的推移，我們將不得不看到，但很難就可能發生的情況下結論或可能發生在一個季度內。

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增長空間，我們仍然看到該類別的增長相當可觀。

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

我們的下一個問題來自 Christopher Raymond 和 Piper Sandler 的觀點。

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?

另一個問題可能是關於 VEGF 市場和 EYLEA 的具體問題。因此，在我們的檢查中，我們感覺到有些醫生認為 susvimo 具有不同的療效，但另一方面，仍有相當數量的醫生在第一次給藥後尚未見患者進行隨訪.有點好奇，如果在現場，你會看到經驗時間對 susvimo 的看法有所不同。他們對更耐心的隨訪的看法有任何明顯的變化嗎？

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 [Roche] 最好回答他們聽到的關於我們的問題。我只是在這一點上分享，我還沒有聽說過這種描述。使用仍然處於低水平，實際上相當適中。我可以描述 EYLEA 的表現，就像我在市場領導地位和我們在市場份額和其他參數方面看到的業務增長方面所做的那樣。這跨越了適應症，並且肯定在很大程度上創造了 EYLEA 作為抗 VEGF 類別的領導者。顯然，我們和視網膜社區一樣非常熱情，如果將來獲得批准，可能對阿柏西普 8 毫克的可能性和潛力更為重要。

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

我們的下一個問題來自瑞銀的克里斯托弗·肖特（Christopher Schott）。

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?

祝賀本季度。所以在 23 年的 EYLEA 上，開始看到一些處方更新。所以我想知道你能否談談你如何看待第 23 季度市場份額的變化，因為 susvimo 然後顯然是生物仿製藥？然後就像我們考慮今年下半年的高劑量價值一樣，任何事情您可以說預期的運營支出變化嗎？

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.

因此，作為開始，我們不預測未來的市場份額表現。因此，我將遠離該領域的細節。當然，不僅在本季度，而且在幾個季度中，我們已經能夠展示 EYLEA 作為抗 VEGF 類別領導者的持續強勁表現，當然，我們將繼續努力。並且隨著代理商進入市場，我們的競爭準備能力已經非常強大。但坦率地說，最重要的是 EYLEA 的概況、臨床屬性、產品的安全性、適應症的廣度、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，我們當然會非常準備推出 8 毫克阿柏西普。隨著我們可能在獲得 FDA 批准的情況下進入該產品發布，我們將能夠提供更多表徵，但正如 George 和 Len 今天所描述的，我們在 aflibercept 8 毫克和視網膜社區的意見領袖中看到的概況證實了這一點profile 可能具有成為護理標準的所有成分。當然，這就是我們將致力於實現視覺的所有好處，再加上安全性以及現在在該類別中從未見過的這種實質性耐用性的潛力。

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，我是鮑勃。關於運營支出，我的意思是 Marion 和我將做我們一直在品牌上做的事情。我們將看看什麼是完全有意義的。我的意思是，如你所知，這是一種確定數量的視網膜文檔。所以這並不是說我們要進入一個非常新的領域，在上面創造很多新的接觸點。最重要的是，Marion 的團隊現在是一個運作非常緊密的銷售代表團隊，在他們的遊戲中處於領先地位。再說一次，我們不期望在這個領域出現一些巨大的轉變。但同樣，我們將確保我們為此提供適當的資金，並且它的商業方面將與臨床數據的支持程度相匹配。

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

我們的下一個問題來自於 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.

祝賀持續的執行和創新。關於前列腺雙特異性，既然您已經有更多時間處理不斷變化的數據，那麼您對那裡的反應或持久性預測因素有何看法？我很好奇你的學習如何影響你對治療窗口的最新想法，無論是在你加速試驗註冊時的 PSMA 還是你的其他共刺激雙特異性藥物。

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，隨著我們看到的顯著反應率，尤其是在更高的劑量下——這並不是說你必須努力尋找反應的生物標誌物。請記住，只是提醒您，在最高劑量下，4 名患者中有 3 名有非常深刻的反應。所以反應預測變量不一定是問題，但你也指出了關於治療窗口的問題。當然，我們看到了與這些反應相關的自身免疫相關副作用。

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.

所以我們現在正在努力工作。實際上，我們已經加快了該計劃的註冊速度。我們正試圖更多地了解反應者之間的關係以及這些自身免疫性副作用。我的意思是一個非常積極的觀點是我們沒有看到這些嚴重的自身免疫副作用和沒有看到反應的人。因此，受益的人確實會產生自身免疫性副作用。這些顯然是耦合的。這是因為我認為藥物正在做我們打算做的事情。我認為這是免疫療法歷史上最令人興奮的數據之一遠，持久的反應。

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。就更廣泛的雙特異性計劃而言，我想回顧一下，Len 有點回答了前面關於 CD20 和 BCMA 的問題。但我確實想放大其中一些評論，也就是說，我們認為在 CD20 領域和 BCMA 領域確實存在非常少的雙規範，它們實際上看起來彼此之間相當有競爭力，包括我們的。新出現的數據表明，這些藥物的療效和安全性將相互競爭。我們將看到我們將在 ASH 上展示的更新數據。但我認為正在出現的是，這些少數競爭者將存在於這個領域。

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.

我認為這些都會有空間。實際上，在這些晚期環境中，有很多患者需要治療。所以我認為這些少數競爭對手會有空間。但未來將是關於進入更早的治療線，關於如何執行、設計這些研究、聯合療法，以及在那裡使用的更標準的聯合療法，將會有[微妙之處]。因此，如何將這些藥物轉移到早期的治療線中將會有很多實際的藝術。但另一件非常重要的事情是，除了使用這些更標準的組合進入早期治療線之外，正如我所說，進行這些研究將是（聽不清）組合，並且正如我們剛剛談到的 CD20 和 costim 雙特異性藥物，我們現在已經證明我們在前列腺癌領域處於領先地位。我們現在有非常相似的類型藥物，我們將與我們的 CD20 雙特異性淋巴瘤和我們的 BCMA 雙特異性骨髓瘤結合。我們認為這些將真正有機會繼續改變遊戲規則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.

所以這是關於在這些晚期環境中採取確實具有競爭力並且相互競爭的代理，我認為他們都將為這些患者的治療做出重要貢獻，但隨後非常巧妙地進入這些早期治療方法的方法並在那裡使用它們，我認為在那裡也會有空間，但總會有差異化的空間以及未來。我們正在利用我們投資組合中的所有這些令人興奮的機會進行這些組合，可以真正將這些藥物的利用以及對這些患者和這些癌症的治療提升到一個全新的水平，因為我們相信我們已經表明我們'正在做前列腺癌。

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，有一個關於前列腺癌生物標誌物的問題。也許您可能只是評論人們在接觸這兩種藥物後在研究中使用 PSA 的速度有多快。

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.

正確的。我們已經展示的一些數據，我們將繼續展示我們的許多患者的 PSA 水平非常高，因為眾所周知，他們的疾病負擔非常高，這取決於化驗和實驗室等，正常的 PSA 水平在個位數到低個位數，也許 1 到 4 被認為是最高水平。我們有數百名、500 名、600 名等進入我們研究的患者。我們看到，一旦您將組合加入，基本上在我們在 3 週左右內測量的下一個時間點，我們就看到了這種組合治療，我們看到 PSA 下降了 99% 的數量級。這些都是非常驚人的結果。現在，隨著時間的推移，我們將繼續跟踪患者。例如，我們已經看到，骨損傷已經完全正常化等等。因此，正如 PSA 所反映的那樣，效果非常迅速。

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，無論您是否有患者的 PSA 負擔相對較低，他們的 PSA 測量值在 40 到 50 範圍內，或者您是否有令人難以置信的在 500 到 600 範圍內的高 PSA，這些患者似乎在開始治療後幾週內 PSA 非常顯著非常顯著下降方面做出了類似的反應。

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.

隨著我們繼續跟踪這些患者，令人難以置信的持久反應是第一位患者現在已經出院一年多了。他們的免疫副作用已經解決，而他們的完全緩解仍然完全完好無損。正如我所說，不僅使 PSA 水平完全正常化，而且骨病變等也都正常化了，至少通過骨掃描等測量。所以這真的 - 對於這些在這一點上真的沒有其他真正追索權的晚期患者來說，有可能改變遊戲規則。

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

謝謝你，倫，喬治。我想我們還有時間再問一個問題，托旺達。

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

我們的最後一個問題來自於 Barclays 的 Carter Gould。

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?

也許只是回到 - 對於 Marion，我們應該如何考慮您對明年收到高劑量 EYLEA 的 J 代碼的時間線的期望。過去，我們在 Libtayo 方面看到了非常不同的時間線，幾乎立即就發生了轉變，羅氏顯然有一個更有節奏的流程。而且我想更重要的是，我們是否應該期望這更像是 2024 年 1 月 1 日類型的事件？還是在 23 年後期可能會出現 J 代碼？

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.

感謝你的提問。當然，我們會在這方面保持密切聯繫。顯然，新 BLA 和新 J 代碼的重要性很重要。在時間方面，我需要一個水晶球。當然，我們會與您分享。我們將與適當的組織和官員密切合作。但在這個時候，對 J-code 時序的期望給出任何明確的結論還為時過早。

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。在 Len 中，我的意思是我自己的觀點，我只是稍微不同的是，我不相信在這個特定的環境中 J 代碼就像交易的結束——就像你會看到這些J-code 後的吸收量發生了巨大變化。

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。我想這就是我們今天的全部時間。謝謝大家加入電話會議。與往常一樣，投資者關係部隨時為您提出任何後續問題。祝大家有個美好的一天。

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。感謝您的參與。您現在可以斷開連接