雷傑納榮製藥 (REGN) 2019 Q3 法說會逐字稿

Good morning, and welcome to the Regeneron Pharmaceuticals Third Quarter 2019 Earnings Conference Call. My name is Sheryl, and I will be your operator for today's call. (Operator Instructions) Please note that this conference call is being recorded.

早安，歡迎參加 Regeneron Pharmaceuticals 2019 年第三季財報電話會議。我叫謝麗爾，我將擔任您今天通話的接線生。（操作員說明）請注意，本次電話會議正在錄音。

I will now turn the call over to Justin Holko. Sir, you may begin.

現在我將把通話交給賈斯汀·霍爾科。先生，您可以開始了。

Thank you, Sheryl. Good morning, good afternoon and good evening to everyone listening around the world. Thank you for your interest in Regeneron Pharmaceuticals, and welcome to the Third Quarter 2019 Conference Call. An archive of this webcast will be available on our website.

謝謝你，謝麗爾。全世界的聽眾朋友們，早安、下午好、晚上好！感謝您對 Regeneron Pharmaceuticals 的關注，歡迎參加 2019 年第三季電話會議。本次網路直播的錄影檔案將會發佈在我們的網站上。

Joining me today on the call are Dr. Leonard Schleifer, Founder, President and Chief Executive Officer; Dr. George Yancopoulos, Founding Scientist, President and Chief Scientific Officer; Marion McCourt, Senior 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.

今天與我一起參加電話會議的有：創始人、總裁兼首席執行官 Leonard Schleifer 博士；創始科學家、總裁兼首席科學官 George Yancopoulos 博士；高級副總裁兼商業主管 Marion McCourt；以及執行副總裁兼首席財務官 Bob Landry。在我們發言完畢後，我們將開放問答環節。

I would also like to remind you that remarks made on this call today include forward-looking statements about Regeneron. Such statements may include but are not limited to those related to Regeneron and its products and business, financial forecast and guidance, development programs and related anticipated milestones, collaborations, finances, regulatory matters, payer coverage and reimbursement issues, intellectual property, pending litigation and competition. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-Q for the quarterly period ended September 30, 2019, which has been filed with the SEC today. Regeneron does not undertake any obligation to update publicly any forward-looking statements whether as a result of new information, future events or otherwise.

我還要提醒各位，今天電話會議上發表的言論包含 Regeneron 的前瞻性陳述。此類聲明可能包括但不限於與 Regeneron 及其產品和業務、財務預測和指導、開發計劃和相關預期里程碑、合作、財務、監管事項、支付方覆蓋範圍和報銷問題、智慧財產權、未決訴訟和競爭相關的聲明。每項前瞻性聲明都存在風險和不確定性，可能導致實際結果和事件與該聲明中預測的結果和事件有重大差異。有關這些及其他重大風險的更完整描述，請參閱 Regeneron 向美國證券交易委員會提交的文件，包括其截至 2019 年 9 月 30 日的季度報告（10-Q 表格），該報告已於今日提交給美國證券交易委員會。無論是由於新資訊、未來事件或其他原因，Regeneron 均不承擔公開更新任何前瞻性聲明的義務。

In addition, please note that GAAP and non-GAAP measures will be discussed on today's call. Information regarding our use of non-GAAP financial measures and a reconciliation of those measures to GAAP is available in our financial results press release, which can be accessed on our website.

此外，請注意，今天的電話會議將討論GAAP和非GAAP指標。有關我們使用非公認會計準則財務指標以及這些指標與公認會計準則的調節表的信息，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查閱。

Once our call concludes, Bob Landry and the IR team will be available to answer further questions.

通話結束後，鮑伯·蘭德里和投資者關係團隊將回答進一步的問題。

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

接下來，我將把電話交給我們的總裁兼執行長倫·施萊弗博士。

Thanks, Justin. Thanks to everyone who's joining the call today. We had another great quarter, marked by continued execution, to deliver double-digit top and bottom line growth while making progress with our innovative R&D engine. EYLEA global net sales grew 14% to $1.9 billion, including U.S. EYLEA net sales growth of 16% to $1.2 billion. We continued to build on our leadership position in retinal diseases with market share gains across wet age-related macular degeneration and diabetic eye diseases.

謝謝你，賈斯汀。感謝今天所有參加電話會議的人。我們又迎來了一個非常棒的季度，這得益於我們持續高效的執行力，實現了兩位數的營收和利潤成長，同時我們的創新研發引擎也取得了進展。EYLEA 全球淨銷售額成長 14% 至 19 億美元，其中美國 EYLEA 淨銷售額成長 16% 至 12 億美元。我們在視網膜疾病領域繼續鞏固領先地位，在濕性老年黃斑部病變和糖尿病眼疾方面獲得了市場份額。

DUPIXENT continued to deliver strong growth while transforming the lives of thousands of patients around the world suffering from a number of Type 2 inflammatory diseases. Global net sales of DUPIXENT are now annualizing at more than $2.5 billion. Launches in atopic dermatitis, asthma and chronic rhinosinusitis with nasal polyps are generating broad-based growth for this important brand. We're still in the early days of DUPIXENT as approvals around the world continue and our enthusiasm continues to increase.

DUPIXENT 持續保持強勁成長勢頭，同時改變了世界各地成千上萬患有多種 2 型發炎性疾病的患者的生活。DUPIXENT 的全球淨銷售額目前已超過 25 億美元。針對異位性皮膚炎、氣喘和伴隨鼻息肉的慢性鼻竇炎的上市，為這個重要品牌帶來了廣泛的成長。DUPIXENT 目前仍處於早期階段，世界各地的審批工作仍在繼續，我們的熱情也與日俱增。

Through the strength of the performance of DUPIXENT, we generated improved profitability for our own -- for our antibody collaboration with Sanofi. We expect profits to continue to increase, further diversifying our earnings base driven by growth in DUPIXENT as well as effective cost management across the collaboration.

憑藉 DUPIXENT 的出色表現，我們提高了自身的盈利能力——也提高了我們與賽諾菲的抗體合作的盈利能力。我們預計利潤將繼續成長，在 DUPIXENT 成長的推動下，我們的收入基礎將進一步多元化，同時在整個合作過程中有效控製成本。

Importantly, our efforts in oncology are bearing fruit in the form of global launches of Libtayo, our anti-PD-1 therapy in cutaneous squamous cell carcinoma; as well as new data from Libtayo in lung cancer; and our portfolio of innovative bispecific antibodies, including our BCMA antibody in multiple myeloma. We aim to be a leader in immuno-oncology by bringing important new treatments to patients with both blood and solid tumor cancers.

重要的是，我們在腫瘤學領域的努力正在取得成果，例如在全球範圍內推出了用於治療皮膚鱗狀細胞癌的抗 PD-1 療法 Libtayo；以及 Libtayo 在肺癌治療方面的新數據；還有我們創新的雙特異性抗體產品組合，包括用於治療多發性骨髓瘤的 BCMA 抗體。我們的目標是成為免疫腫瘤學領域的領導者，為血液腫瘤和實體腫瘤患者帶來重要的全新療法。

Beyond oncology, we have novel programs that have generated significant late-stage results that we intend to file with regulators, such as evinacumab in homozygous familial hypercholesterolemia. Similarly, results from the PALM study in the Democratic Republic of Congo demonstrated that our antibody combination was superior to the standard of care in preventing death from Ebola in the recent outbreak. We expect further pipeline readouts by the end of the year as George will speak to in a few moments.

除了腫瘤學領域，我們還有一些創新項目，這些項目已經取得了顯著的後期成果，我們打算向監管機構提交申請，例如用於治療純合子家族性高膽固醇血症的 evinacumab。同樣，剛果民主共和國的 PALM 研究結果表明，我們的抗體組合在預防伊波拉疫情中的死亡方面優於標準療法。我們預計到今年年底會有更多管道數據公佈，喬治稍後會就此發表演說。

Taken together, we continue to demonstrate that Regeneron has the talent and track record to tackle some of the world's most scientifically challenging health issues while creating long-term value for shareholders. We continue to execute on our strategy, and a result -- and as a result, are in a strong financial position. We think carefully about how -- about our capital and how to deploy it strategically.

綜上所述，我們不斷證明 Regeneron 擁有解決世界上一些最具科學挑戰性的健康問題的才能和業績，同時為股東創造長期價值。我們繼續執行我們的策略，並取得了成果——因此，我們擁有強勁的財務狀況。我們會認真思考如何利用我們的資本以及如何進行策略性部署。

As such, we will continue to invest in R&D, as we have shown that those investments have generated significant value for shareholders and for patients. Business development efforts will continue as we seek the best science and capabilities to pair with our own innovations. Beyond R&D, and based upon our confidence in the business to deliver value both in the short and longer term, we are initiating a $1 billion stock buyback program.

因此，我們將繼續投資研發，因為我們已經證明，這些投資為股東和患者創造了巨大的價值。我們將繼續努力拓展業務，尋求最先進的科學技術和能力，以與我們自身的創新結合。除了研發之外，基於我們對公司在短期和長期內創造價值的信心，我們正在啟動一項 10 億美元的股票回購計畫。

These are exciting times for Regeneron. We have strong momentum as we head into the end of the year and into 2020.

對於再生元公司來說，這是一個令人興奮的時刻。進入2020年並邁入2020年，我們擁有強勁的發展勢頭。

Now I'll turn the call over to George.

現在我把電話交給喬治。

Thanks, Len. I will begin with DUPIXENT. There is nothing more gratifying than hearing directly from so many individuals about how DUPIXENT changed their lives after years of suffering from diseases such as asthma, atopic dermatitis and nasal polyposis. Just last week, a co-worker shared her story, how she was dreading her fourth surgery for nasal polyposis and instead convinced her doctor to try DUPIXENT. Not only did her nasal polyposis vanish without surgery, but her co-morbid asthma also dramatically improved.

謝謝你，Len。我先從DUPIXENT說起。沒有什麼比直接聽到這麼多人講述 DUPIXENT 如何改變了他們多年來飽受哮喘、異位性皮膚炎和鼻息肉等疾病折磨的生活更令人欣慰的了。就在上週，一位同事分享了她的故事，她原本很害怕接受第四次鼻息肉手術，但最終說服了她的醫生嘗試使用 DUPIXENT。她的鼻息肉不僅無需手術就消失了，而且同時患有的氣喘也得到了顯著改善。

Such stories reflect the science behind DUPIXENT. Many patients suffer from a body-wide hyperactivation of the Type 2 immune pathway, which manifests in disease at many different sites, including the lungs, skin, upper respiratory system and even GI tract. DUPIXENT can be life-changing as it can reverse the systemic Type 2 hyperactivity, thus simultaneously treating multiply apparent, distinct disease entities.

這些案例反映了DUPIXENT背後的科學原理。許多患者患有全身性 2 型免疫通路過度激活，導致肺部、皮膚、上呼吸道甚至胃腸道等多個部位出現疾病。DUPIXENT 可以改變人生，因為它能逆轉 2 型系統性過度活躍，從而同時治療多種明顯的、不同的疾病實體。

The other remarkable aspect of DUPIXENT is its safety profile. Since Type 2 hyperactivity is often counterproductive, DUPIXENT is not immunosuppressive. Across all of our studies, we have not seen increases in serious infections. In fact, in our AD studies, where people are prone to skin infections, we actually have seen a numeric decrease in infections.

DUPIXENT的另一個顯著特點是其安全性。由於 2 型過度活躍往往適得其反，因此 DUPIXENT 不具有免疫抑製作用。在我們所有的研究中，都沒有發現嚴重感染病例增加。事實上，在我們的 AD 研究中，在那些容易發生皮膚感染的人群中，我們確實觀察到感染數量有所下降。

The DUPIXENT opportunity is growing in several ways by expanding to new territories to younger age groups into new Type 2 diseases. For example, the nasal polyposis indication was recently approved by the European Commission. We are submitting for atopic dermatitis in the pediatric population later this year and we are enrolling Phase III studies in eosinophilic esophagitis and chronic obstructive pulmonary disease. In addition, there are numerous ongoing or soon to be initiated trials in additional Type 2 diseases, including bullous pemphigoid, prurigo nodularis, chronic spontaneous urticaria, hand and foot atopic dermatitis, alopecia areata and allergic bronchopulmonary aspergillosis.

DUPIXENT 的機會正在以多種方式增長，包括擴展到新的地區、更年輕的年齡群體以及新的 2 型疾病。例如，鼻息肉適應症最近已獲得歐盟委員會批准。我們將於今年稍後提交兒童異位性皮膚炎的申請，並且我們正在進行嗜酸性食道炎和慢性阻塞性肺病的 III 期研究。此外，還有許多正在進行或即將開始的試驗針對其他 2 型疾病，包括大皰性類天皰瘡、結節性癢疹、慢性自發性蕁麻疹、手足異位性皮膚炎、斑禿和過敏性支氣管肺麴菌病。

We're also very excited about the potential of DUPIXENT to accelerate and enhance allergen desensitization. Our combination trial with the immunotherapy for grass allergy will be presented at a future medical conference. And data in combination with Aimmune's AR101 for peanut allergy are planned for late next year. Related to our DUPIXENT efforts, we are expecting a readout of our interleukin-33 antibody, Regeneron 3500, in atopic dermatitis and COPD over the coming year.

我們對 DUPIXENT 在加速和增強過敏原脫敏方面的潛力也感到非常興奮。我們將在未來的醫學會議上發表我們針對草過敏的免疫療法聯合試驗結果。結合 Aimmune 的 AR101（用於治療花生過敏）的數據計劃於明年年底公佈。就我們的 DUPIXENT 研發工作而言，我們預計在未來一年內將公佈我們的白細胞介素-33 抗體 Regeneron 3500 在異位性皮膚炎和 COPD 治療中的療效結果。

As you know, DUPIXENT is currently approved for uncontrolled moderate-to-severe asthma and atopic dermatitis and is approved in earlier stages of these diseases. However, because of its efficacy and safety profile, including the lack of immunosuppression, we believe DUPIXENT can have an important benefit earlier in these diseases, where biologics have thus not -- thus far not been utilized. And we are considering studying DUPIXENT in patients with these earlier stages of disease.

如您所知，DUPIXENT 目前已獲準用於治療未控制的中度至重度氣喘和異位性皮膚炎，並且已獲準用於治療這些疾病的早期階段。然而，由於其療效和安全性，包括不抑制免疫反應，我們相信 DUPIXENT 可以在這些疾病的早期階段發揮重要的益處，而生物製劑迄今尚未在這些疾病中使用。我們正在考慮對處於疾病早期階段的患者進行DUPIXENT的研究。

Now we'll turn to our immuno-oncology efforts. First, I want to remind you how challenging it is to create best-in-class biologicals and how often failure is still the rule. The foundation for Regeneron's success over the years has been our technology platforms that we have repeatedly used to produce first-in-class or best-in-class biologics, whether EYLEA for eye diseases, PRALUENT for heart disease, DUPIXENT for allergic Type 2 diseases or the recent stunning success with our Ebola antibody cocktail. I need not remind you that in all of these settings, there were very few, if any, successful competitors. Instead, numerous competitors, including some of the biggest biopharma companies in the world, failed. And now we feel that we can create similar advantage by bringing our next-generation technologies to immuno-oncology.

現在我們將轉向免疫腫瘤學方面的工作。首先，我想提醒大家，創造一流的生物製劑是多麼具有挑戰性，失敗仍然屢見不鮮。多年來，Regeneron 取得成功的基礎是我們反覆使用的技術平台，這些平台生產出同類首創或同類最佳的生物製劑，無論是用於治療眼部疾病的 EYLEA、用於治療心臟病的 PRALUENT、用於治療 2 型過敏性疾病的 DUPIXENT，還是最近在埃博拉抗體雞尾酒療法方面取得的驚人成功。我無需提醒各位，在所有這些情況下，幾乎沒有成功的競爭對手。相反，包括一些全球最大的生物製藥公司在內的眾多競爭對手都失敗了。現在我們認為，透過將我們的下一代技術應用於免疫腫瘤學領域，我們可以創造類似的優勢。

Arguably the biggest advance in this field has been PD-1 blockade. But even here, most efforts to develop PD-1 or PD-L1 blockers have not produced best-in-class results, with Merck's pembrolizumab being a clear outlier. Moreover, even with this best-in-class PD-1 blocker, most cancers do not respond. And for those that do, only a fraction of the patients have satisfactory response. We are very far from curing cancer in general. This is why we feel that with our technological advantages, we can make a major contribution.

可以說，該領域最大的進展是 PD-1 阻斷。但即便如此，大多數開發 PD-1 或​​ PD-L1 阻斷劑的努力也沒有取得同類最佳的結果，默克的帕博利珠單抗顯然是個例外。此外，即使使用這種一流的 PD-1 阻斷劑，大多數癌症也無反應。即使接受治療，也只有一小部分患者能獲得滿意的療效。我們距離徹底治癒癌症還很遙遠。正因為如此，我們認為憑藉我們的技術優勢，我們可以做出重大貢獻。

First of all, we believe we can use our VelocImmune human/mouse, the widely acknowledged gold standard for making fully human antibodies, to make best-in-class checkpoint blockers such as for PD-1. Moreover, we have developed a next-generation VelocImmune mouse that, when combined with our recently described Veloci-Bi platform can produce the most natural antibody-like bispecifics more rapidly and routinely than other approaches. Our bispecifics naturally have long half lives without complex engineering, without mutations and can be delivered like normal antibodies without requiring constant infusion. This has allowed us to emerge as a leader in the so-called CD3 bispecific space, in which a bispecific can be used to link a killer T cell to a tumor target.

首先，我們相信我們可以使用我們的 VelocImmune 人類/鼠抗體（公認的製造全人源抗體的黃金標準）來製造一流的檢查點阻斷劑，例如 PD-1 阻斷劑。此外，我們開發了一種新一代的VelocImmune小鼠，當與我們最近描述的Veloci-Bi平台結合使用時，可以比其他方法更快、更常規地生產出最天然的抗體樣雙特異性抗體。我們的雙特異性抗體天然具有較長的半衰期，無需複雜的工程改造，無需突變，並且可以像普通抗體一樣進行遞送，而無需持續輸注。這使我們能夠成為所謂的 CD3 雙特異性領域的領導者，在該領域中，雙特異性抗體可用於將殺傷性 T 細胞與腫瘤標靶連接起來。

Moreover, we have invented what we believe is the next important class of bispecifics, which we call co-stimulatory, or co-stim, bispecifics that can synergize with both our PD-1 antibody and with our CD3 bispecifics. We believe that progress in cancer will require amplifying and deepening the responses and settings where PD-1 antibody is already active as well as activating responses where PD-1 has little or no activity, such as in prostate, pancreatic, colorectal and other settings. We hope that our bispecifics will demonstrate such synergies together as well as with our PD-1 antibody.

此外，我們發明了我們認為的下一類重要的雙特異性抗體，我們稱之為共刺激或共刺激雙特異性抗體，它可以與我們的 PD-1 抗體和 CD3 雙特異性抗體產生協同作用。我們認為，癌症治療的進展需要增強和深化 PD-1 抗體已發揮作用的治療效果和適應症，以及激活 PD-1 抗體作用甚微或沒有作用的治療效果，例如在前列腺癌、胰腺癌、結直腸癌和其他癌症治療中。我們希望我們的雙特異性抗體能夠彼此之間以及與我們的 PD-1 抗體之間展現出協同作用。

We have already begun establishing the individual efficacy profiles of our 3 classes of immuno-oncology agents. In terms of our PD-1 antibody, Libtayo, we defied expectations by identifying important new cancer setting where PD-1 therapy had not previously been characterized despite the broad efforts in the field. We obtained rapid approval in cutaneous squamous cell carcinoma, or CSCC, based on some of the best response rates yet described for a PD-1 block into a solid tumor setting, approaching 50% in late-stage metastatic and locally advanced CSCC. While others have subsequently explored their PD-1 therapies in this setting, Libtayo remains the first and only approved therapeutic in advanced CSCC, and based on cross-study comparisons, has an outstanding efficacy profile.

我們已經開始建立我們3類免疫腫瘤藥物的個人療效概況。就我們的 PD-1 抗體 Libtayo 而言，我們出乎意料地發現了重要的全新癌症領域，儘管該領域已進行了廣泛的努力，但 PD-1 療法此前並未在該領域得到充分研究。我們憑藉在實體腫瘤治療中 PD-1 阻斷療法取得的極佳療效，在皮膚鱗狀細胞癌 (CSCC) 中迅速獲得批准，在晚期轉移性和局部晚期 CSCC 中療效接近 50%。雖然其他研究者隨後也探索了 PD-1 療法在這種治療環境下的應用，但 Libtayo 仍然是目前唯一獲批用於治療晚期 CSCC 的療法，根據交叉研究的比較，它具有出色的療效。

We believe non-melanoma skin cancers represent an important previously untapped opportunity, and we are working to expand our leading position in this space. A registrational study in adjuvant CSCC is already ongoing. In addition, Dr. Neil Gross of MD Anderson recently presented exciting early results with Libtayo in neoadjuvant CSCC with 70% response rates and 55% complete pathological responses. And we are now planning a larger new adjuvant study.

我們認為非黑色素瘤皮膚癌代表著一個以前未開發的重要機遇，我們正在努力擴大我們在該領域的領先地位。一項針對輔助治療性皮膚鱗狀細胞癌的註冊研究已經展開。此外，MD安德森癌症中心的尼爾·格羅斯博士最近公佈了Libtayo在CSCC新輔助治療中令人興奮的早期結果，有效率達70%，病理完全緩解率達55%。我們現在正計劃進行一項更大規模的輔助治療研究。

We're also looking forward to a potentially pivotal data in the first half of 2020 for another -- from another important common skin cancer where PD-1 therapies have not been extensively characterized. That is basal cell carcinoma. Finally for skin cancers, we're also exploring Libtayo in melanoma in various combination studies intended to show increased benefit over PD-1 therapy alone.

我們也期待在 2020 年上半年獲得另一項可能具有關鍵意義的數據——來自另一種重要的常見皮膚癌，PD-1 療法尚未得到廣泛的表徵。那就是基底細胞癌。最後，對於皮膚癌，我們也正在探索 Libtayo 在黑色素瘤中的應用，進行各種聯合研究，旨在證明其療效優於單獨使用 PD-1 療法。

Beyond skin cancers, we are working to establish Libtayo as a therapeutic in non-small cell lung cancer, the largest current PD-1 opportunity. Along these lines, earlier today, we provided an update on our lung study with Libtayo monotherapy in high PD-L1 expressers. This 700-patient study is now over 90% enrolled. Based on an early interim analysis of overall survival in about 1/3 of anticipated events, the IDMC recommended continuing the trial as planned.

除了皮膚癌之外，我們正在努力將 Libtayo 確立為非小細胞肺癌的治療藥物，這是目前 PD-1 治療領域最大的機會。今天早些時候，我們更新了 Libtayo 單藥治療高 PD-L1 表現患者的肺部研究結果。這項涉及 700 名患者的研究目前已完成 90% 以上的入組。根據對約 1/3 預期事件的總體生存率進行的早期中期分析，獨立數據監察委員會 (IDMC) 建議按計劃繼續進行試驗。

We also announced that in the first 361 randomized patients, the confirmed objective response rate as determined by the investigators is currently 42% Libtayo versus 22% for chemotherapy. These objective response findings, while not sufficient for regulatory approval in this setting, support our hope that Libtayo may prove an important therapeutic and non-small cell lung cancer. The next event-driven interim analysis for overall survival is anticipated in 2020.

我們也宣布，在前 361 名隨機分組的患者中，研究人員確定的確認客觀緩解率目前為：Libtayo 組 42%，化療組 22%。雖然這些客觀反應結果不足以獲得該領域的監管批准，但它們支持了我們的希望，即 Libtayo 可能成為治療非小細胞肺癌的重要藥物。下一次以事件驅動的總體存活期中期分析預計將於 2020 年進行。

In terms of other important phase -- in terms of our other important Phase III study in lung cancer, which is comparing Libtayo with chemotherapy versus chemotherapy alone. We expect full enrollment in the second half of next year.

在其他重要階段方面—在我們另一項重要的肺癌 III 期研究方面，該研究比較了 Libtayo 聯合化療與單獨化療的效果。我們預計明年下半年將有全面招生。

As with our PD-1 antibody, we are also establishing the efficacy and safety profile of bispecifics first as single agents. Starting with our CD3-class of bispecifics, we have already reported that Regeneron 1979, our CD20xCD3 bispecific, demonstrated impressive single-agent response rates in late-stage lymphoma patients, including in those that have failed CAR-T therapy.

與我們的 PD-1 抗體一樣，我們也首先確定雙特異性抗體作為單一療法的療效和安全性。從我們的 CD3 類雙特異性抗體開始，我們已經報導過，我們的 CD20xCD3 雙特異性抗體 Regeneron 1979 在晚期淋巴瘤患者中表現出令人印象深刻的單藥反應率，包括 CAR-T 療法失敗的患者。

At the European Hematology Association meeting, based on a small number of patients, we reported 93% objective response rates with 71% complete responses in late-stage follicular lymphoma and reported 57% response rates in late-stage diffuse large B-cell lymphoma patients, including 2 responses in 4 patients that had failed CAR-T therapy.

在歐洲血液學協會會議上，我們根據少量患者報告，晚期濾泡性淋巴瘤的客觀緩解率為 93%，完全緩解率為 71%；晚期瀰漫性大 B 細胞淋巴瘤患者的緩解率為 57%，其中包括 4 例 CAR-T 療法失敗的患者中的 2 例緩解。

While the ASH abstracts that we'll be posting tomorrow will only include older data, our presentation at ASH will include additional patients in longer duration of follow-up with about 20 patients at effective dose levels for each of follicular lymphoma and DLBCL. We have already initiated a potentially pivotal Phase II study which intends to enroll independent arms with different subtypes of non-Hodgkin lymphoma.

雖然我們明天發布的 ASH 摘要只包含較早的數據，但我們在 ASH 上的報告將包含更多隨訪時間更長的患者，其中濾泡性淋巴瘤和 DLBCL 各有約 20 名患者達到有效劑量水平。我們已經啟動了一項可能具有關鍵意義的 II 期研究，該研究計劃招募患有不同亞型非何杰金氏淋巴瘤的獨立患者群。

In terms of our BCMAxCD3 bispecific, based on early single-agent proof of concept data that we will present at ASH, we are encouraged about the potential of this treatment for multiple myeloma. Remind you that the abstracts -- the ASH abstract posting tomorrow will also reflect all the data, including only our first dosing level with the BCMA bispecific. We look forward to updating these results with promising new data from our second dosing cohort at ASH.

就我們的 BCMAxCD3 雙特異性抗體而言，根據我們將在 ASH 上展示的早期單藥概念驗證數據，我們對這種治療多發性骨髓瘤的潛力感到鼓舞。提醒各位，摘要－明天發布的 ASH 摘要也將反映所有數據，包括我們使用 BCMA 雙特異性抗體的第一個劑量水平。我們期待在 ASH 會議上，用來自第二組給藥隊列的有希望的新數據來更新這些結果。

Finally, our third CD3 bispecific, MUC16xCD3, continues in a trial as a single agent and will shortly start a combination phase with Libtayo.

最後，我們的第三種 CD3 雙特異性抗體 MUC16xCD3 正在作為單一藥物進行試驗，並將很快開始與 Libtayo 聯合用藥的試驗階段。

In terms of the first example of our entirely novel class of so-called co-stim bispecifics, our PCMAxCD28 bispecific, we have begun dosing patients in recently initiated combinations with Libtayo. In this prostate cancer setting, which is normally not responsive to PD-1, we hope that our PCMAxCD28 bispecific can trigger responses as it has in preclinical studies.

就我們全新類別的所謂共刺激雙特異性抗體的第一個例子而言，我們的 PCMAxCD28 雙特異性抗體，我們已經開始在最近啟動的與 Libtayo 的聯合治療中給患者用藥。在前列腺癌這種通常對 PD-1 沒有反應的環境中，我們希望我們的 PCMAxCD28 雙特異性抗體能夠像在臨床前研究中引發反應。

In summary, we are very excited that the initial entries for our 3 different classes of immuno-oncology therapeutics are establishing their individual potentials, and we are entering into the next stage, exploring combinations.

總而言之，我們非常高興看到我們 3 類不同的免疫腫瘤療法的初步試驗結果正在展現出各自的潛力，我們正在進入下一階段，探索聯合療法。

In terms of combinations, we're not limiting ourselves to our internal portfolio. Our external immuno-oncology collaborations fall into 2 broad categories: Cell therapy, including CAR-Ts and other approaches; and vaccine-like approaches. Once again, these all have the potential of being explored individually but also in combination with our PD-1 and other checkpoint inhibitors as well as with our 2 classes of bispecifics. Altogether, we believe we are making significant progress on our strategy to become a leader in the immuno-oncology space.

在組合方面，我們並不局限於我們內部的產品組合。我們的外部免疫腫瘤學合作分為兩大類：細胞療法，包括 CAR-T 療法和其他療法；以及疫苗樣療法。再次強調，這些藥物都有可能單獨進行研究，也可以與我們的 PD-1 和其他檢查點抑制劑以及我們的 2 類雙特異性抗體結合使用。總而言之，我們相信我們在成為免疫腫瘤學領域領導者的策略上取得了重大進展。

I would like to finish with brief discussions updating our ophthalmology efforts and also briefly touch on our rare disease portfolio. For EYLEA, we are planning registrational clinical programs in wet AMD and DME, evaluating a novel and higher-dose formulation of 8 milligrams in 8-week -- sorry, in 12-week and 16-week regimens. The Phase II trial in wet AMD is underway. Beyond EYLEA, we are continuing preclinical development of a new VEGF blocker, gene therapy and other novel approaches, including with our Alnylam collaborators.

最後，我想簡要介紹我們眼科領域的工作進展，並簡要介紹我們的罕見疾病項目。對於 EYLEA，我們計劃在濕性 AMD 和 DME 中開展註冊臨床項目，評估一種新型高劑量配方，劑量為 8 毫克，療程為 8 週——抱歉，是 12 週和 16 週。濕性老年黃斑部病變的第二期臨床試驗正在進行中。除了 EYLEA 之外，我們也持續進行新的 VEGF 阻斷劑、基因療法和其他新方法的臨床前開發，包括與我們的 Alnylam 合作者合作。

We have also made substantial progress in our rare disease portfolio. In mid-2020, we are planning a regulatory submission for evinacumab in homozygous familial hypercholesterolemia based on Phase III data showing nearly 50% LDL reduction in patients already treated with statins and PCSK9s. By the end of 2019, we're also expecting a readout of garetosmab for fibrodysplasia ossificans progressiva. And we are becoming increasingly excited about our C5 program.

我們在罕見疾病領域也取得了實質進展。2020 年年中，我們計劃根據 III 期數據，向監管機構提交 evinacumab 用於治療純合子家族性高膽固醇血症的申請。數據顯示，在已接受他汀類藥物和 PCSK9 治療的患者中，evinacumab 可使 LDL 降低近 50%。到 2019 年底，我們也將獲得 garetosmab 治療進行性骨化性纖維發育不良的試驗結果。我們對我們的C5專案越來越感到興奮。

Let remind you, we set a very high bar for entry into existing markets with novel agents. In the case of C5, our goal was to achieve convenient self-administration with a subcutaneous dosage form as well as more complete blockade of inappropriate complement activation. We are encouraged by our progress towards these goals and plan to present our first data for our C5 antibody, pozelimab, in paroxysmal nocturnal hemoglobinuria patients at a future medical conference. We're also exploring options for combination with cemdisiran, a novel SRNA developed by our Alnylam collaborators.

再次提醒各位，我們對新代理商進入現有市場設定了非常高的進入門檻。對於 C5，我們的目標是實現皮下給藥形式的便捷自我給藥，並更徹底地阻斷不適當的補體活化。我們對實現這些目標所取得的進展感到鼓舞，並計劃在未來的醫學會議上公佈我們針對陣發性睡眠性血紅蛋白尿症患者的 C5 抗體 pozelimab 的首批數據。我們也正在探索與 cemdisiran 結合的可能性，cemdisiran 是由我們的 Alnylam 合作者開發的新型 SRNA。

In closing, this is a very interesting time to be at Regeneron. Now we'll turn the call over to Marion.

總之，現在是加入 Regeneron 的絕佳時機。現在我們把電話交給瑪莉安。

Thank you, George. We continued to execute well in the third quarter led by our core EYLEA and DUPIXENT businesses as well as promising Libtayo market introduction.

謝謝你，喬治。第三季度，在核心業務安理國際 (EYLEA) 和度普利尤單抗 (DUPIXENT) 以及前景可觀的利普泰優 (Libtayo) 市場推廣的帶動下，我們繼續保持良好的業績。

Starting with EYLEA. Global net product sales grew 14% year-over-year to $1.9 billion. In the U.S., net product sales grew to $1.2 billion. This represents 16% year-over-year growth. A combination of overall market growth and share gains drove strong third quarter performance of EYLEA. Growth in the overall market continues at a mid- to high single-digit range, underpinned by the aging population and increase in diabetes prevalence. EYLEA's share of the branded market also increased to 73% of net product sales for the quarter driven by physician preference for EYLEA. We continue to invest in EYLEA to advance our market-leading position across all indications.

從愛麗莎開始。全球淨產品銷售額年增 14%，達到 19 億美元。在美國，產品淨銷售額成長至 12 億美元。這相當於年增16%。整體市場成長和市佔率提升共同推動了安永第三季的強勁業績。受人口老化和糖尿病盛行率上升的推動，整體市場持續保持中高個位數成長。由於醫生對 EYLEA 的偏好，EYLEA 品牌市佔率在本季淨產品銷售額中也成長至 73%。我們將繼續投資安永，以鞏固我們在所有適應症領域的市場領先地位。

Let me take a moment to remind you of select strategic commercial initiatives to enhance our market-leading position in wet AMD and further penetrate diabetic eye disease, where there is significant growth opportunity. In wet AMD, we are growing our position by focusing on EYLEA's rapid and sustained outcomes to improve and protect vision. Wet AMD currently represents just under 60% of EYLEA business and EYLEA continues to grow in this patient group.

請容許我花一點時間提醒各位，我們採取了一些策略性商業舉措，以鞏固我們在濕性 AMD 領域的市場領先地位，並進一步滲透到糖尿病眼疾領域，該領域存在著巨大的成長機會。在濕性 AMD 領域，我們專注於 EYLEA 的快速和持續療效，以改善和保護視力，從而鞏固我們的地位。濕性老年黃斑部病變目前佔 EYLEA 業務的近 60%，EYLEA 在該患者群體中的業務持續成長。

In diabetic eye disease, our expanded field team is making tremendous strides. Our strategy is to increase diagnosis and treatment rates by educating health care professionals, consumer awareness and applying technologies to support diagnosis. With approximately 15% of the market receiving an anti-VEGF treatment, there's an important opportunity to help patients preserve and improve their vision. Our growth in DME indicates our strategy is delivering results.

在糖尿病眼疾領域，我們擴大的現場團隊正在取得巨大進展。我們的策略是透過教育醫療保健專業人員、提高消​​費者意識和應用技術支援診斷來提高診斷率和治療率。約有 15% 的市場接受了抗 VEGF 治療，這為幫助患者保護和改善視力提供了一個重要的機會。我們在DME領域的成長顯示我們的策略正在取得成效。

Our diabetic retinopathy launch is off to an encouraging start, with EYLEA use increasing in both proliferative disease and severe non-proliferative disease. We anticipate EYLEA use to increase as retina specialists see the benefits of actively treating these patients.

我們的糖尿病視網膜病變產品上市取得了令人鼓舞的開端，EYLEA 在增殖性疾病和嚴重非增殖性疾病的使用量均有所增加。我們預計，隨著視網膜專家看到積極治療這些患者的好處，EYLEA 的使用量將會增加。

Finally, we plan to launch the EYLEA prefilled syringe before the end of this year. Taken together, EYLEA has compelling efficacy and safety, breadth of indications, dosing flexibility and clinical and real-world experience.

最後，我們計劃在今年年底前推出EYLEA預充式註射器。綜合來看，EYLEA 具有令人信服的療效和安全性、廣泛的適應症、靈活的給藥方式以及臨床和真實世界經驗。

Turning to oncology. We're commercializing Libtayo with Sanofi. Global net sales of Libtayo were $52 million, including $4 million from our recent ex U.S. market launches that began this quarter. In the U.S., we continue to establish Libtayo as a standard of care across all lines of therapy for advanced cutaneous squamous cell carcinoma, or CSCC. Libtayo is now the #1 systemic CSCC treatment in terms of total patients. It is outperforming chemotherapy and has made rapid share gains within the anti-PD-1 class, where Libtayo has 80% share in new patients. We expect growth to continue based on demographics, enhancements in patient identification and referrals.

轉向腫瘤學。我們正在與賽諾菲合作，將Libtayo商業化。Libtayo 的全球淨銷售額為 5,200 萬美元，其中包括本季開始的近期在美國以外市場推出的 400 萬美元。在美國，我們繼續將 Libtayo 確立為晚期皮膚鱗狀細胞癌 (CSCC) 所有治療方案的標準療法。就患者總數而言，Libtayo 現在是排名第一的 CSCC 系統性治療藥物。它的療效優於化療，並在抗 PD-1 類藥物中迅速獲得了市場份額，Libtayo 在新患者中佔據了 80% 的市場份額。我們預計，基於人口結構變化、患者識別和轉診的改進，成長將持續下去。

In addition, recent updates to the National Comprehensive Cancer Network, or NCCN guidelines, list Libtayo as the preferred single-agent systemic option. Libtayo is the only CSCC, anti-PD-1 treatment with a 2A recommendation. Ex U.S. launches in CSCC are currently underway in multiple markets, including Germany, the U.K. and Brazil. While early, we are seeing encouraging progress on access and reimbursement as well as prescribing trends and physician interest.

此外，美國國家綜合癌症網絡（NCCN）指南的最新更新將利妥昔單抗列為首選的單藥全身治療方案。Libtayo 是唯一獲得 2A 級建議的 CSCC 抗 PD-1 治療藥物。目前，CSCC 在美國以外的多個市場正在進行推廣，包括德國、英國和巴西。雖然還處於早期階段，但我們在獲取途徑、報銷、處方趨勢和醫生興趣方面都看到了令人鼓舞的進展。

Moving to PRALUENT. In the second quarter, global net sales were $70 million. We are working diligently with our collaborator Sanofi to address brand profitability.

遷移至 PRALUENT。第二季度，全球淨銷售額為 7,000 萬美元。我們正與合作夥伴賽諾菲密切合作，努力提升品牌獲利能力。

Turning to KEVZARA. In the third quarter, global net sales were $55 million. In the U.S., we see steady growth as KEVZARA continues to make headway in the IL-6 subcutaneous class, with 48% share of new-to-brand prescriptions and 30% share of total prescriptions.

轉向 KEVZARA。第三季度，全球淨銷售額為 5,500 萬美元。在美國，我們看到 KEVZARA 在 IL-6 皮下注射劑領域持續取得進展，實現了穩步增長，其新品牌處方份額為 48%，總處方份額為 30%。

Now for DUPIXENT, which is transforming the lives of patients suffering from many Type 2 inflammatory diseases. Global net product sales in the third quarter were $633 million. In the U.S., net product sales reached $508 million, representing 131% year-over-year growth. Total prescriptions in the U.S. grew approximately 21% compared to the second quarter. We continue to see strong prescribing trends across all approved indications. Weekly new-to-brand prescriptions for the third quarter averaged approximately 1,350 patients per week, up from 1,200 in the prior quarter.

現在來說說 DUPIXENT，它正在改變許多 2 型發炎性疾病患者的生活。第三季全球淨產品銷售額為 6.33 億美元。在美國，淨產品銷售額達到 5.08 億美元，年增 131%。美國處方總量較第二季成長約 21%。我們持續看到所有核准適應症的處方量呈現強勁成長趨勢。第三季每週新開處方藥的患者平均約 1,350 人次，高於上一季的 1,200 人次。

In atopic dermatitis, DUPIXENT continues to outpace other biologic launches in dermatology. For adults, we are pleased to see an increased number of patients with moderate disease being prescribed DUPIXENT earlier in the treatment paradigm and ahead of immunosuppressant therapy. We see ample opportunity in atopic dermatitis as approximately 20% of adult patients with the greatest need have used DUPIXENT. Additionally, our ongoing launch in adolescents continues to contribute meaningfully to the brand.

在異位性皮膚炎領域，DUPIXENT 繼續超越其他皮膚科生物製劑的上市速度。對於成年患者，我們很高興看到越來越多的中度疾病患者在治療方案的早期階段，在免疫抑制劑治療之前，就被處方了 DUPIXENT。我們看到異位性皮膚炎領域存在著很大的機會，因為大約 20% 的成年患者（他們最需要這種藥物）已經使用過 DUPIXENT。此外，我們在青少年族群中持續進行的推廣活動也持續為品牌做出重要貢獻。

As a reminder, DUPIXENT is the first biologic approved for atopic dermatitis in adolescents, many of whom remained uncontrolled using topical therapies. This launch has been aided by physician experience with the efficacy and safety and adults.

需要提醒的是，DUPIXENT 是第一個獲準用於治療青少年異位性皮膚炎的生物製劑，許多青少年使用局部療法仍無法控制病情。此次上市得益於醫師們在成人病患的療效和安全性方面的經驗。

In asthma, DUPIXENT in positioned to capitalize on this significant market opportunity. Approximately 75% of DUPIXENT asthma patients are new to biologics, demonstrating our ability to grow this market. Prescribing trends are accelerating among both allergists and pulmonologists. With only 15% of eligible patients being treated with a biologic, there's significant opportunity to educate patients about DUPIXENT. As a result, last month, we initiated our asthma direct-to-consumer TV campaign.

在氣喘領域，DUPIXENT 已做好充分準備，抓住這一巨大的市場機會。約 75% 的 DUPIXENT 氣喘患者是首次使用生物製劑，這顯示我們有能力拓展這一市場。過敏科醫生和肺科醫生的處方趨勢都在加速成長。由於只有 15% 的符合條件的患者接受了生物製劑治療，因此有很大的機會向患者普及 DUPIXENT 的相關知識。因此，上個月，我們啟動了氣喘直接面向消費者的電視廣告宣傳活動。

Finally, our launch in chronic rhinosinusitis with nasal polyps is going extremely well. Encouragingly, patients are being initiated on DUPIXENT regardless of prior surgery. As a reminder, in the U.S., up to 90,000 adults with this disease are considered uncontrolled despite prior surgery or systemic corticosteroid use. About 55,000 patients have had prior surgery. While early in the launch, we believe this will be a meaningful growth opportunity for DUPIXENT.

最後，我們針對慢性鼻竇炎伴隨鼻息肉的治療方案的推出進展非常順利。令人鼓舞的是，無論之前是否接受過手術，患者都可以開始接受 DUPIXENT 治療。提醒大家，在美國，儘管之前接受過手術或使用過全身性皮質類固醇，但仍有多達 90,000 名患有這種疾病的成年人病情未被控制。約有 55,000 名患者曾接受過手術。雖然目前還處於上市初期，但我們相信這將是 DUPIXENT 的一個重要成長機會。

We have an unprecedented opportunity with DUPIXENT in Type 2 inflammatory diseases. The number of physicians prescribing is growing. And with more than 100,000 patients globally treated with DUPIXENT, the outlook remains exceedingly positive.

DUPIXENT 為我們在 2 型發炎性疾病領域帶來了前所未有的機會。開處方的醫生人數正在增加。目前全球已有超過 10 萬名患者接受了 DUPIXENT 治療，前景依然非常​​樂觀。

In closing, the commercial organization delivered a solid performance in the third quarter. We have the right strategy and we are executing to deliver short- and long-term growth.

總之，商業部門在第三季取得了穩健的表現。我們擁有正確的策略，並且正在執行該策略，以實現短期和長期成長。

Now I'll turn the call over to Bob.

現在我把電話交給鮑伯。

Thanks, Marion. For the third quarter 2019, Regeneron delivered double-digit growth on the top and bottom lines driven by strong performance from both EYLEA and DUPIXENT and increased profitability within the Sanofi Alliance. Total revenues for Regeneron grew 23% year-over-year to $2.05 billion driven by continued growth of our core brands, EYLEA and DUPIXENT. Non-GAAP diluted net income per share grew 14% year-over-year to $6.67 on non-GAAP net income of $762 million.

謝謝你，瑪莉安。2019 年第三季度，Regeneron 的營收和利潤均實現了兩位數成長，這主要得益於 EYLEA 和 DUPIXENT 的強勁表​​現以及賽諾菲聯盟內部獲利能力的提高。受核心品牌 EYLEA 和 DUPIXENT 的持續成長推動，Regeneron 的總營收年增 23%，達到 20.5 億美元。非GAAP稀釋後每股淨收益年增14%至6.67美元，非GAAP淨收益為7.62億美元。

Since Marion discussed our EYLEA results in the U.S., I will start with our Bayer and Sanofi collaborations. Starting with the Bayer collaboration. Ex U.S. EYLEA net product sales, which are reported to us by Bayer, were $730 million, representing a 12% reported and a 14% constant currency basis increase year-over-year. Total Bayer collaboration revenue for the third quarter of 2019 grew 15% year-over-year to $303 million, of which $275 million was derived from our share of net profits from EYLEA sales outside the U.S.

既然 Marion 已經討論了我們在美國開展的 EYLEA 計畫成果，那麼我將從我們與拜耳和賽諾菲的合作開始談起。從與拜耳的合作開始。根據拜耳公司向我們報告，除美國以外，EYLEA淨產品銷售額為7.3億美元，按報告匯率計算年增12%，以固定匯率計算年增14%。2019 年第三季拜耳合作總營收年增 15% 至 3.03 億美元，其中 2.75 億美元來自我們在美國以外地區銷售 EYLEA 產品所獲得的淨利份額。

Total Sanofi collaboration revenue was $404 million, up 58% year-over-year, as commercial profitability improved sharply. For the third quarter of 2019, Regeneron recognized a profit of $94 million in connection with the commercialization of non IO antibodies compared to a loss of $39 million in the prior year period and a profit of $39 million in the second quarter of this year. Both the year-over-year and sequential increase was driven by higher DUPIXENT profits. As we head into the end of the year and into 2020, we expect continued improved profitability driven by strong DUPIXENT net sales growth, continued cost containment on PRALUENT and KEVZARA and improvements in our operating leverage.

賽諾菲合作計畫總收入為 4.04 億美元，年增 58%，商業獲利能力大幅提高。2019 年第三季度，再生元公司確認非 IO 抗體商業化帶來的利潤為 9,400 萬美元，而去年同期虧損 3,900 萬美元，今年第二季獲利 3,900 萬美元。年比和環比成長均由 DUPIXENT 利潤成長推動。隨著我們進入年底和 2020 年，我們預計在 DUPIXENT 淨銷售額強勁增長、PRALUENT 和 KEVZARA 成本持續控制以及經營槓桿改善的推動下，盈利能力將繼續提高。

Turning now to expenses. Non-GAAP R&D expenses were $603 million for the third quarter of 2019 compared to $497 million for the third quarter of 2018, an increase of 22%. We are continuing to invest in our pipeline and research capabilities which is critical to the long-term success of the business.

接下來談談費用。2019 年第三季非 GAAP 研發費用為 6.03 億美元，而 2018 年第三季為 4.97 億美元，成長了 22%。我們將繼續投資我們的產品線和研發能力，這對企業的長期成功至關重要。

Our oncology pipeline continues to forge ahead, and we are advancing several wholly owned molecules into clinical development with more to come. In addition, we are funding external partnership obligations as jointly developed molecules are rapidly advancing. While we are not yet giving guidance for 2020, we anticipate non-GAAP R&D expenses to increase.

我們的腫瘤藥物研發管線持續推進，我們正在將幾個自主研發的分子推進到臨床開發階段，未來將有更多分子進入臨床開發。此外，由於共同開發的分子正在快速推進，我們正在為外部合作義務提供資金。雖然我們尚未給出 2020 年的業績指引，但我們預期非 GAAP 研發費用將會增加。

Our non-GAAP unreimbursed R&D expense, which is calculated as the total non-GAAP R&D expense less R&D reimbursements from our collaborators, was $441 million for third quarter 2019 compared to $311 million for the third quarter of 2018. Based on the current forecast for the remainder of the year, we are tightening our previous full year 2019 guidance for non-GAAP unreimbursed R&D to $1.68 billion to $1.71 billion.

2019 年第三季度，我們的非 GAAP 未報銷研發費用（計算方法為非 GAAP 研發總費用減去合作方的研發報銷）為 4.41 億美元，而 2018 年第三季為 3.11 億美元。根據今年剩餘時間的當前預測，我們將先前對 2019 年全年非 GAAP 未報銷研發的預期收緊至 16.8 億美元至 17.1 億美元。

Next, non-GAAP SG&A expense was $379 million for the third quarter of 2019, a 16% year-over increase driven by higher headcount and related costs and launch-related expenses for U.S. Libtayo and for new indications for EYLEA and DUPIXENT. We are tightening our previous full year 2019 guidance for non-GAAP SG&A to $1.55 billion to $1.58 billion.

其次，2019 年第三季非 GAAP SG&A 費用為 3.79 億美元，年成長 16%，主要原因是人員增加及相關成本，以及美國 Libtayo 上市相關費用和 EYLEA 和 DUPIXENT 新適應症的上市相關費用。我們將 2019 年全年非 GAAP 銷售、一般及行政費用預期收緊至 15.5 億美元至 15.8 億美元。

Sanofi reimbursement of Regeneron commercialization-related expenses, line items found within Sanofi collaboration revenue, was $115 million for the third quarter of 2019. Based on spending trends and cost containment efforts related to PRALUENT and KEVZARA, we are lowering and tightening our previous full year 2019 guidance for Sanofi reimbursement of Regeneron commercialization-related expenses to $490 million to $510 million.

2019 年第三季度，賽諾菲向 Regeneron 支付的商業化相關費用（包含在賽諾菲合作收入中的項目）為 1.15 億美元。根據與 PRALUENT 和 KEVZARA 相關的支出趨勢和成本控制措施，我們將先前對賽諾菲 2019 年全年 Regeneron 商業化相關費用報銷的預期下調並收緊至 4.9 億美元至 5.1 億美元。

In the third quarter of 2019, combined non-GAAP cost of goods sold and cost of collaboration and contract manufacturing were $210 million compared to $102 million in the third quarter of 2018. The year-over-year increase in cost of goods sold was primarily due to the company's obligation to pay Sanofi its share of Libtayo U.S. gross profits, lower fixed cost absorption and higher inventory reserves and write-offs. The year-over-year increase in cost of collaboration and contract manufacturing was primarily due to recognition of manufacturing costs associated with higher sales of DUPIXENT.

2019 年第三季度，非 GAAP 銷售成本和合作及合約製造成本總計為 2.1 億美元，而 2018 年第三季為 1.02 億美元。銷售成本年增主要是由於公司有義務向賽諾菲支付其應得的 Libtayo 美國毛利潤份額、固定成本吸收減少以及庫存準備金和減值增加。合作和合約製造成本同比增加主要是由於確認了與 DUPIXENT 銷量增加相關的製造成本。

Turning now to taxes. For the third quarter of 2019, our GAAP effective tax rate was 12.9% compared to 6.5% for the third quarter of 2018. Based on our actual results to date and forecast for the remainder of the year, we are raising our full year 2019 GAAP effective tax rate guidance to 12% to 14%. We continue to expect our full year 2019 non-GAAP tax rate to be higher than our full year 2019 GAAP effective tax rate.

接下來談談稅務問題。2019 年第三季度，我們的 GAAP 實際稅率為 12.9%，而 2018 年第三季為 6.5%。根據我們迄今為止的實際業績和今年剩餘時間的預測，我們將 2019 年全年 GAAP 有效稅率預期上調至 12% 至 14%。我們仍預期 2019 年全年非 GAAP 稅率將高於 2019 年全年 GAAP 實際稅率。

Turning next to our cash flow and balance sheet. Year-to-date, we've generated $1.35 billion in free cash flow, defined as net cash provided by operating activities less capital expenditures. We ended the third quarter of 2019 with cash and marketable securities of nearly $6 billion.

接下來我們來看現金流量表和資產負債表。今年迄今為止，我們已產生 13.5 億美元的自由現金流，自由現金流定義為經營活動產生的現金淨額減去資本支出。截至 2019 年第三季末，我們持有現金及有價證券近 60 億美元。

Earlier today, we announced a $1 billion share repurchase program. With that announcement, let me take a moment to discuss our capital allocation priorities. In terms of capital deployment, investing in our internal research capabilities and advancing our pipeline remains our top priority. As evident by our productivity and the high returns we've generated historically on our R&D, these investments are critical for our business and shareholders.

今天早些時候，我們宣布了一項10億美元的股票回購計畫。有鑑於此，我想花一點時間談談我們的資本配置重點。在資金部署方面，投資於我們的內部研發能力和推進我們的產品線仍然是我們的首要任務。從我們的生產力和我們歷來在研發方面獲得的高回報來看，這些投資對我們的業務和股東至關重要。

Second, we seek to complement our internal efforts with external strategic partnerships and collaborations. Over the last 18 months, we've funded in excess of $900 million in equity and upfront payments, comprising more than 5 new strategic opportunities in the areas of RNAi therapeutics, oncolytic viruses and CAR-T therapies. Following these R&D investments, we assess additional strategic uses of our cash.

其次，我們尋求透過外部策略夥伴關係和合作來補充我們的內部努力。在過去的 18 個月裡，我們投入超過 9 億美元的股權和預付款，涵蓋了 RNAi 療法、溶瘤病毒和 CAR-T 療法等領域的 5 個以上的新策略機會。在這些研發投資之後，我們將評估現金的其他策略用途。

Our overall business is growing with increasingly diversified revenue and cash flow streams. Coupled with the strength of our balance sheet and our confidence in the long-term outlook for the business, we view share buybacks at current trading levels as an efficient use of capital.

我們的整體業務正在成長，收入和現金流來源日益多元化。鑑於我們穩健的資產負債表以及對公司長期前景的信心，我們認為在當前交易水準下進行股票回購是有效利用資本的方式。

In conclusion, we are very pleased with our financial results and performance this quarter. With continued execution on our R&D and commercial strategies, we are positioned for long-term growth.

總之，我們對本季的財務表現和表現非常滿意。透過持續執行我們的研發和商業策略，我們已為長期成長做好準備。

With that, I'd like to turn the call back to Justin.

那麼，我想把電話轉回給賈斯汀。

Thank you, Bob. Sheryl, that concludes our prepared remarks. We'd now like to open the call for Q&A.

謝謝你，鮑伯。謝麗爾，我們的演講稿到此結束。現在我們開始問答環節。

(Operator Instructions) Our first question comes from Chris Raymond from Piper Jaffray.

（操作說明）我們的第一個問題來自 Piper Jaffray 公司的 Chris Raymond。

So just maybe a question on the EYLEA franchise. And maybe just from a high-level perspective, you guys have been framing your next-generation efforts in a pretty similar way, I think, for a few quarters now. And so the high-dose formulations in the clinic now, which I think is new. But your discussion on the other mechanisms still seem to be framed in the same way that you had the last few quarters.

所以，我有個關於EYLEA系列的問題。或許從宏觀角度來看，我認為你們在過去幾個季度裡，對下一代工作的規劃方式都相當相似。所以現在臨床上出現了高劑量製劑，我認為這是一種新的現象。但是，你對其他機制的討論似乎仍然和過去幾季一樣，沒有改變。

And so I guess the question is I'm wondering if you can talk about where -- when we might see something from these novel mechanisms in the clinic. And maybe talk about these efforts in the context of the IP runway you have with EYLEA.

所以我想問的是，您能否談談我們何時才能在臨床上看到這些新機制的應用？或許可以結合安永的智慧財產權儲備來談談這些努力。

And then maybe a second part of the question, can you describe more tactically any continued impact from the supply hiccups of compounded Avastin on the quarter?

那麼，問題的第二部分可能是，您能否更具體地描述一下，複合型阿瓦斯汀的供應中斷對本季造成的任何持續影響？

So Marion will take any comments about the Avastin supply issues. Let me just say that -- I'm not going to comment on our patent situation here. I can say one thing for sure, is that our data exclusivity runs some ways into 2024, so we have a reasonable runway there.

所以，Marion會接受任何關於阿瓦斯汀供應問題的意見。我只想說——我不會對我們的專利情況發表評論。我可以肯定地說，我們的數據獨家使用權可以持續到 2024 年，所以我們還有相當長的時間。

In terms of timing, obviously, we're working hard. We tend, Chris, not to predict when things will finally go into the clinic. But as soon as they do, we will let you know. We're hard at work at it. And the one that we mentioned, the high-dose, the new formulation, is now underway in our Phase II program.

就時間安排而言，顯然，我們正在努力。克里斯，我們通常無法預測病情何時最終會發展到臨床階段。但一旦有消息，我們會立即通知您。我們正在努力實現這個目標。我們提到的高劑量新配方目前正在我們的 II 期臨床試驗中進行。

Marion, you want to comment on the Avastin situation?

瑪莉昂，你想對阿瓦斯汀的情況發表一下看法嗎？

Sure, Len. And just to comment, in the third quarter, there were some temporary spot shortages of Avastin in select geographies, so they may have given some modest benefit to EYLEA. We mentioned the same in the second quarter. And the one thing I can add is that we are hearing that patients that are started on Avast -- excuse me, started on EYLEA because of these shortages do continue on EYLEA therapy. So we'll continue to monitor the situation, which is episodic. And of course, in many instances, are related to ongoing issues with compounding and quality concerns.

當然，萊恩。另外補充一點，第三季度，部分地區出現了阿瓦斯汀的暫時性短缺，這可能為安永帶來了一些輕微的好處。我們在第二季也提到這一點。我還可以補充一點，我們聽說，由於這些短缺，開始使用 Avast（抱歉，應該說是 EYLEA）的患者確實繼續接受 EYLEA 治療。因此我們將繼續關注這一時斷時續的情況。當然，在許多情況下，這些問題都與配藥和品質方面的持續問題有關。

Our next question comes from Ronny Gal from Bernstein.

我們的下一個問題來自伯恩斯坦公司的羅尼·加爾。

A couple, if you don't mind. First, on the CD3xCD20. George, it looks like you might have actually got here with Roche. Can you comment a little bit about your -- the -- kind of how you differentiate your program from the [Marcelin] program, the [developed] program?

如果你不介意的話，我想跟你分享一下。首先，在 CD3xCD20 上。喬治，看來你確實是跟羅氏公司一起來的。您能否稍微談談您的專案與馬塞林專案（Marcelin program）或已開發的專案有何不同？

And are you going straight into first line with this? Or are you still thinking it's going to be in a relapse setting for the next set of trial?

你是打算直接把這個放到第一行嗎？還是你仍然認為下一輪試驗將在復發環境下進行？

And if you can remind us whether the partnership with Sanofi gives them the right to enter this program? Or is it still at your control. And given you're now in a kind of an excess cash situation, you have more choice about what you're going to do with this?

請問您能否提醒我們一下，與賽諾菲的合作關係是否賦予了他們參與該計畫的權利？或者，它仍然在你的掌控之中？鑑於你現在手邊比較寬裕，你對如何使用這筆錢就有了更多選擇？

Well, maybe I'll start at the back because it's the easiest. It's a wholly owned program that we control and nobody has an option on it. Number one.

嗯，或許我會從後面開始，因為這樣最容易。這是一個完全由我們掌控的自主項目，任何人都沒有選擇權。第一。

Number two, in terms of the comparisons with Roche, I mean, obviously, these are cross-trial comparisons. But we're very encouraged with how our data looks and how we both have a -- how we have a chance to have best-in-class potential. One of the most important things, we believe, about not only this program but our immuno-oncology franchise in general, is that we have, we believe, an unparalleled opportunity to generate synergistic therapeutics that can work very powerfully together. So we are certainly going to be exploring our CD20xCD3 in combination with our PD-1 antibody, Libtayo, which we're very interested in. But also, we have an assortment of additional bispecifics in the settings where one might need additional efficacy. We believe that we can add to it, and we've certainly shown that and demonstrated that in preclinical models.

第二，就與羅氏的比較而言，我的意思是，顯然，這些是跨試驗的比較。但我們對數據的表現以及我們雙方——我們雙方——都有機會擁有業內最佳潛力感到非常鼓舞。我們認為，不僅對於這個項目，而且對於我們整個免疫腫瘤學領域而言，最重要的一點是，我們擁有一個無與倫比的機會，可以開發出能夠協同發揮強大作用的療法。因此，我們肯定會探索將我們的 CD20xCD3 與我們的 PD-1 抗體 Libtayo 結合使用，我們對此非常感興趣。此外，在可能需要額外療效的情況下，我們還有一系列其他的雙特異性抗體。我們相信我們可以在此基礎上有所貢獻，而且我們已經在臨床前模型中證明了這一點。

So we think that, that's what really differentiates us, is that we really have a lot of tools in our tool kits a lot of possibilities for combining a lot of things with synergistic capabilities together. In addition to the fact that each one of our individual agents, we believe that based on the emerging data, has a chance to be best-in-class. And we're moving very aggressively into a near-term pivotal, approvable trials. And we'll be moving into earlier stages as well.

所以我們認為，真正讓我們與眾不同的是，我們的工具包裡有很多工具，有很多可能性可以將很多東西結合起來，發揮協同效應。除了我們每個經紀人都有可能成為一流人才之外，根據不斷湧現的數據，我們相信他們每個人都有機會成為一流人才。我們正積極推動近期關鍵性、可獲批准的試驗。我們也將進入更早的階段。

Certainly, it's Len, just to echo what George said. We feel good about our position, but we don't take Roche lightly. They're a formidable -- Roche/Genentech are a formidable competitor with lots of experience in the CD20 space. But they may have historical approaches that may be -- might be disruptible by new agents and combinations.

當然，正如喬治所說，是倫。我們對自己的地位感到滿意，但我們不會輕視羅氏。他們是強大的競爭對手——羅氏/基因泰克是強大的競爭對手，在 CD20 領域擁有豐富的經驗。但他們的歷史方法可能會被新的因素和組合所顛覆。

Our next question comes from Geoff Meacham from Bank of America.

下一個問題來自美國銀行的傑夫‧米查姆。

Just have a couple for Bob. I wanted to ask about the commercialization-related expenses. Was this just lower reimbursable expenses to Regeneron? Or is it related to, say, DUPI profitability? Or is this sort of -- should be looked at as the next phase of the JV expense base overall?

給鮑伯留幾個。我想詢問一下與商業化相關的費用。這是否意味著 Regeneron 可報銷的費用降低了？或者這與 DUPI 的獲利能力有關嗎？或者，這應該被視為合資企業整體費用基礎的下一個階段？

And then for George. Obviously, you've got Libtayo-chemo combos going and CTLA-4 combos going, but how much of a priority is it to test more novel mechanisms with PD-1, just given recent data from AZ and Bristol?

然後是喬治。顯然，目前已經有了利妥昔單抗-化療聯合療法和 CTLA-4 聯合療法，但考慮到 AZ 和 Bristol 最近發表的數據，測試更多 PD-1 的新機制究竟有多重要？

Geoff, I'll start. Well certainly, with the launch of DUPIXENT in the new indications, I mean we're moving full speed ahead with regards to that. And we've been talking about PRALUENT and KEVZARA cost containment for the last couple of quarters I would say in the third quarter, you're meaning -- we meaningfully saw what we were -- have been working on with our Sanofi counterparts in terms of trying to rein in a little bit with regards to the amount of OpEx associated with PRALUENT and KEVZARA.

傑夫，我先來。當然，隨著 DUPIXENT 在新適應症中的推出，我們在這方面正在全速推進。在過去的幾個季度裡，我們一直在討論 PRALUENT 和 KEVZARA 的成本控制問題。我想說，在第三季度，我們真正看到了我們與賽諾菲的同事一直在努力控制與 PRALUENT 和 KEVZARA 相關的營運支出。

Okay. And so certainly, we're following closely the PD-1 field. As you said, it is evolving. Our goal, as it's been from the beginning, is to have a foundational PD-1 therapeutic that is at least competitive, if not best-in-class. And so we're very excited, for example, about some of the data that we reported on today in terms of the response rates in our first-line monotherapy lung cancer study. But once again, the story is as you said, that we think that we have an enormous opportunity of combining with our novel sets of reagents. Some of which are already in combinations in the clinic not only with the entire assortment of checkpoint inhibitors but also with our entire assortment of bispecifics.

好的。因此，我們當然會密切關注PD-1領域。正如你所說，它正在不斷發展。我們從一開始就設定的目標，就是研發出一種基礎性的 PD-1 療法，使其至少具有競爭力，即使無法成為同類最佳。例如，我們對今天公佈的一線單藥治療肺癌研究的回應率數據感到非常興奮。但正如你所說，我們認為我們有一個巨大的機會，可以與我們新開發的試劑組合結合。其中一些藥物已經在臨床試驗中與所有檢查點抑制劑以及我們所有的雙特異性抗體進行聯合治療。

So as I already mentioned, we're exploring combinations with the bispecifics of the CD3 class that are in the clinic already, but we've already initiated our second class of bispecifics, these co-stimulatory bispecifics, which have the opportunity to activate PD-1 responsiveness in tumors that are not normally responsive to PD-1. So not only can they enhance responsiveness in tumors that are responding to some degree already, but they can actually endow responsiveness in those that don't in preclinical models. And we hope that, that pertains, obviously, in the clinic. This creates, we think, a great way of extending the benefit that immuno-oncology has already provided by taking it deeper in cancers that are already responsive, but also opening up cancers that haven't responded to date.

正如我之前提到的，我們正在探索與臨床中已使用的 CD3 類雙特異性抗體的組合，但我們已經啟動了第二類雙特異性抗體，即共刺激雙特異性抗體，它們有機會激活通常對 PD-1 沒有反應的腫瘤的 PD-1 反應性。因此，它們不僅可以增強已經產生一定程度反應的腫瘤的反應性，而且實際上還可以使那些在臨床前模型中沒有反應的腫瘤產生反應性。我們希望這一點，顯然也適用於臨床實務。我們認為，這為擴大免疫腫瘤學已經帶來的益處提供了一種很好的方法，不僅可以更深入地治療已經產生反應的癌症，還可以治療迄今為止尚未產生反應的癌症。

So I do want to just emphasize again, why do we have this ability? Because we have a unique platform for making these bispecifics. As far as I'm aware, we're the only platform that couples essentially a naturally derived bispecific antibodies using a genetically humanized mouse, together with this Veloci-Bi platform that we recently announced, to rapidly and routinely make natural bispecifics that behave just like normal antibodies.

所以我想再強調一下，為什麼我們要擁有這種能力？因為我們擁有一個獨特的平台來製造這些雙特異性抗體。據我所知，我們是唯一一個將基因改造小鼠中天然來源的雙特異性抗體與我們最近發布的 Veloci-Bi 平台相結合的平台，可以快速、常規地生產出像普通抗體一樣表現的天然雙特異性抗體。

You don't have to give them by constant infusion. You don't have to introduce linkers. You don't have to make mutations in there so that they have longer half lives because they look, and they're manufactured in fact, just like regular antibodies. They behave like them. You can give them normally like you give biologics. You don't have to go to special -- extensive lengths to manufacture them. This allows us to rapidly and routinely make many of these and put them into the clinic very rapidly in these various combinations and target them in exactly the way we want to, in some cases, initiate; or in other cases, trigger or activate a co-response. And I think it's the collection of these put together that allow for very exciting combinations, as I said.

你不需要透過持續輸注的方式給藥。你不需要引入連接子。你不需要對它們進行突變來延長它們的半衰期，因為它們看起來，實際上也是像普通抗體一樣製造出來的。他們的行為和他們一樣。你可以像注射生物製劑一樣正常注射它們。你不需要花太多精力去製造它們。這使我們能夠快速、常規地製造許多此類藥物，並以各種組合方式快速將其投入臨床應用，並按照我們想要的方式進行精準治療，在某些情況下，啟動治療；或者在其他情況下，觸發或激活協同反應。正如我所說，我認為正是這些元素的集合體才能產生非常令人興奮的組合。

Yes, and let me just add something very quickly. Geoff, you also alluded to there were other combinations out there, whether it be CTLA-4, LAG-3 or what have you. We in this field recognize that not all antibodies are created equally. As George said, I mean, you've got some antibody like a KEYTRUDA that worked in first line; and others, let's say, in PD-L1; or others even in PD-1 that may not work as well, didn't work. And so we have to make sure we explore some of these other antibodies, LAG3 or what have you ourselves, to be satisfied that there's not opportunity for a combination therapy there as well.

是的，我再補充一點。傑夫，你也暗示過還有其他組合，像是 CTLA-4、LAG-3 等等。我們這個領域的專家都體認到，並非所有抗體都具有相同的特性。正如喬治所說，我的意思是，有些抗體，例如 KEYTRUDA，在一線治療中有效；而其他一些抗體，例如 PD-L1 抗體；甚至還有一些 PD-1 抗體，可能效果不太好，或者根本無效。因此，我們必須確保我們自己探索一些其他的抗體，例如 LAG3 或其他抗體，以確保沒有機會進行聯合治療。

(Operator Instructions) We still have several callers that we'd like to squeeze in.

（操作員指示）我們還有幾位來電者需要接聽。

Our next question comes from George -- I'm sorry, Geoff Porges from SVB Leerink.

下一個問題來自喬治——抱歉，是 SVB Leerink 的 Geoff Porges。

A quick question. You have 3 products that are -- look like they're annualizing at about $200 million a year in revenue: KEVZARA, Libtayo and PRALUENT. And certainly, Libtayo is still growing strongly. First, Bob, can you give us a sense of whether they're actually contributing to cash flow at that revenue level? And secondly, do you envisage any further changes in the commercial support, the structure behind those products, such that they could enhance the profitability or at least not drag on the profitability of DUPIXENT in the future?

問個問題。你們有 3 款產品，看起來每年的收入約為 2 億美元：KEVZARA、Libtayo 和 PRALUENT。當然，Libtayo 的發展勢頭依然強勁。首先，鮑勃，你能告訴我們，在這樣的收入水平下，它們是否真的對現金流做出了貢獻嗎？其次，您是否設想在商業支援和這些產品背後的結構方面進行任何進一步的改變，以便提高盈利能力，或者至少在未來不會拖累 DUPIXENT 的盈利能力？

Geoff, I'll start. And you can imagine for competitive reasons, we're not going to get into kind of specific products with regards to what they're generating from a cash flow perspective. We've given kind of high-level cover -- color with regards to what the drivers have been. Obviously, DUPIXENT on our current profitability for the quarter.

傑夫，我先來。您可以想像，基於競爭原因，我們不會深入探討具體產品在現金流量方面的表現。我們已經對車手們的情況進行了一些高層次的報道——一些細節方面。顯然，DUPIXENT 對我們本季的獲利能力有影響。

Repeat the second question, the second part of it.

重複第二個問題，也就是它的第二部分。

Yes. Are there any changes that you could envisage in terms of the structure or the spend that, let's say, allow you to capture more of the profitability of DUPIXENT?

是的。就結構或支出而言，您能否設想一些改變，例如，使您能夠獲得更多 DUPIXENT 的盈利能力？

You have sort of faded out at the end. This is Len. But I think what you're asking, can we change the structure or the profitability? I think Sanofi and Regeneron are constantly looking at this. We see the same data you do. It is very early for Libtayo. So that's one thing. It's getting a little bit late for PRALUENT and KEVZARA. And we are focused on making sure we do the right thing overall for the -- so that they're not a drain on the overall alliance. You can be assured of that.

最後你有點淡出了人們的視線。這是倫。但我認為你問的是，我們能否改變結構或獲利能力？我認為賽諾菲和再生元一直在關注這個問題。我們看到的數據和你們看到的一樣。現在對Libtayo來說還為時過早。這是其中一件事。對 PRALUENT 和 KEVZARA 來說，時間已經有點晚了。我們專注於確保我們為聯盟整體做出正確的決定，以免他們成為整個聯盟的負擔。這一點你可以放心。

Our next question comes from Terence Flynn from Goldman Sachs.

下一個問題來自高盛的特倫斯·弗林。

I was just wondering, for your BCMAxCD3 bispecific, are you encouraged because you're seeing activity in a second type of cancer here with the platform or encouraged because you have a competitive efficacy profile relative to the CAR-T and ADC data we've seen from the competitors? And then any commentary you can share at a high level regarding the safety/tolerability profile at this point?

我只是想問一下，對於您的 BCMAxCD3 雙特異性抗體，您是因為在該平台上觀察到對第二種癌症的活性而感到鼓舞，還是因為相對於我們從競爭對手那裡看到的 CAR-T 和 ADC 數據，您的療效具有競爭力而感到鼓舞？那麼，您能否就目前該藥物的安全性/耐受性情況分享一些高層次的評論？

Yes. I think that it's fair to -- I think you made 2 great points. I mean I think, one, it's very important to see that the platform is consistently producing what looked like very competitive, exciting data. And so it's encouraging for that reason. And secondly, if the platform is producing competitive data in a particular area, then it's exciting for that reason as well. So I guess the answer is yes and yes on both of those.

是的。我認為這樣做是公平的——我認為你提出的兩點都很好。我的意思是，我認為，首先，非常重要的是要看到該平台持續產出看起來非常有競爭力、令人興奮的數據。因此，從這個角度來看，這令人鼓舞。其次，如果該平台在特定領域產生具有競爭力的數據，那麼僅憑這一點也令人興奮。所以我想這兩個問題的答案都是肯定的。

We shouldn't go any further. We'll show you the data at ASH.

我們不應該再繼續下去了。我們將在 ASH 會議上向你們展示這些數據。

Our next question comes from Terence -- I'm sorry, the question comes from Matthew Harrison from Morgan Stanley.

下一個問題來自 Terence——抱歉，這個問題來自摩根士丹利的 Matthew Harrison。

George, I just wanted to follow up on some comments you made around C5. I guess, 2 parts here. So first, you mentioned a couple products that you expected at ASH, but you just said a future medical meeting for C5. Should we expect this at ASH? Or is this -- are we not going to see this at ASH? And then you also said that you're encouraged. So should we think about this as something that it looks like you plan to move into pivotal studies at this point?

喬治，我只是想就你之前對 C5 發表的一些評論做個後續說明。我想，這裡有兩個部分。首先，您提到了一些您預計會在 ASH 上推出的產品，但您剛才又說 C5 將在未來的醫學會議上亮相。我們應該期待在ASH會議上看到這種情況嗎？或者說——我們難道不會在ASH上看到這個嗎？然後你還說你受到了鼓舞。所以，我們是否可以認為，您目前似乎計劃進入關鍵性研究階段？

Well as I said, we had a very high bar before we would get excited about it, which was we want to feel like we could change the field. As you know, the current approaches are limited to intravenous delivery. We were looking for a subcutaneous, self-administered approach and we were also looking for more complete suppression of hemolysis. And so we are excited because we feel like we satisfied our high bar.

正如我所說，我們設定了一個很高的標準，只有當我們覺得自己能夠改變這個領域時，我們才會感到興奮。如您所知，目前的方法僅限於靜脈注射。我們當時正在尋找一種皮下注射、患者自行給藥的方法，同時也希望能更徹底抑制溶血。因此我們感到很興奮，因為我們覺得我們達到了自己設定的高標準。

In terms of where we're actually going to present it, we're hoping to present it as soon as possible in a major medical conference. And so that we don't get prevented from presenting it at such conferences, we can't tell you where we're presenting. Sorry about that.

至於我們實際上將在哪裡展示這項研究，我們希望盡快在一個大型醫學會議上進行展示。為了不被阻止在這樣的會議上進行展示，我們不能告訴你我們將在哪裡進行展示。抱歉。

Our next question comes from Yaron Werber from Cowen.

我們的下一個問題來自 Cowen 公司的 Yaron Werber。

Great. So George, maybe just one for you relating to -- give us a sense. In the Phase II high-dose EYLEA study, you're testing 8 milligrams. Can you advance that right away into the parallel Phase III pivotals? Or do you need to show sort of safety first before you can move to a pivotal and the pivotal would have a different dose?

偉大的。喬治，或許你可以問你一個相關的問題──讓我們來感受一下。在第二階段高劑量 EYLEA 研究中，你們正在測試 8 毫克劑量。能否立即推進到並行的 III 期關鍵性試驗階段？或者說，在進行關鍵性試驗之前，是否需要先證明其安全性，而關鍵性試驗的劑量也會有所不同？

And maybe if I can just throw in, any initial feedback on the Beovu launch that you're seeing in the last literally 3 weeks or so?

我可以補充一點嗎？在過去三週左右的時間裡，您對 Beovu 的發布有什麼初步反饋嗎？

I'll leave the last for Marion to comment on. But in terms of the first, of course, there's always safety concerns. But depending on whether one sees something unexpected or not, we are planning to do it exactly as you said. The Phase II is intended to simultaneously be providing data while we're running the Phase III to give us confidence that the high-dose EYLEA is actually performing and doing the things that we're predicting that it would actually do. So we're not limiting the Phase III by the Phase II data.

最後一點，就留給瑪莉安來評論吧。但就第一點而言，當然始終存在安全隱患。但是，如果出現意料之外的情況，我們將按照您所說的去做。第二階段試驗旨在與第三階段試驗同時提供數據，以增強我們對高劑量 EYLEA 實際療效的信心，並驗證其是否達到了我們預期的效果。因此，我們不會用 II 期資料來限制 III 期研究。

And Marion?

瑪麗昂呢？

Sure. And just first, we're pleased with the EYLEA performance through this third quarter and certainly been in a competitive market for some years. But specifically to the most recent launch, Novartis' launch, when you take all the important competition seriously and certainly have been prepared for new market entrants. But it is really early, so we can't report on any impact. We're not seeing any impact at this time. And I think the market will be looking to product profile to determine issues of safety, efficacy and product use.

當然。首先，我們對安永第三季的表現感到滿意，而且多年來我們一直處於競爭激烈的市場中。但具體到最近諾華的上市，你會發現他們非常重視所有重要的競爭對手，並且已經為新的市場進入者做好了準備。但現在還為時過早，所以我們無法報告任何影響。目前我們尚未發現任何影響。我認為市場會關注產品概況，以確定安全性、有效性和產品用途等問題。

Our next question comes from Evan Seigerman from Crédit Suisse.

我們的下一個問題來自瑞士信貸的埃文·塞格曼。

Congrats on the progress. So one for Bob. I was wondering if you could provide us some more color on the rationale for the newly announced share repurchase program. On this, this seems to be kind of a deviation from your prior capital allocation strategy. So why now? Do you believe that your share price is undervalued and that this is the best way to invest capital? Or are there other factors impacting the decision?

恭喜你取得進展。所以，這杯是給鮑伯的。我想請您詳細介紹一下新宣布的股票回購計畫的理由。這一點似乎與你之前的資本配置策略有所不同。那麼，為什麼是現在？您是否認為您的股票價格被低估了，而這是投資資本的最佳方式？或者有其他因素影響這項決定嗎？

Thanks, Evan, for the question. And again, we wanted to be kind of pointed during our script with regards to calling out the framework that we have on this because we do get a lot of questions on it. I think exactly where you kind of ended off on the question with regards to -- we currently like the valuation. Obviously, all the work we do inside here and what we know is coming and...

謝謝埃文的提問。再次強調，我們希望在腳本中明確指出我們在這方面的框架，因為我們確實收到了很多關於這方面的問題。我認為你最後在這個問題上的觀點正是——我們目前對估值感到滿意。顯然，我們在這裡所做的一切工作，以及我們所知道的未來…

Bob, I got to interrupt you. I kind of hate the valuation.

鮑勃，我得打斷一下。我不太喜歡這個估值。

The valuation from a purchasing point of view is what we certainly like. Thanks for that help, Len, on that. We like the levels. And as I tried to point out, I mean, we sufficiently invest in R&D in the right areas. Things continue to move through the clinic. We are also going into external transactions. We mentioned in May the Alnylam transaction, and I talked about a little bit that -- there on the script. So now is the right time with regards to being able to kind of put additional capital to work. And again, to reiterate what you said, we do like -- we think the valuations are attractive from our point of view at this level.

從購買角度來看，這個估值正是我們非常滿意的。謝謝你的幫助，Len。我們喜歡這樣的關卡設計。正如我試圖指出的那樣，我的意思是，我們在正確的領域投入了足夠的研發資金。診所裡各項事務仍在持續進行中。我們也在進行外部交易。我們在五月提到了 Alnylam 的交易，我在劇本裡也稍微談到了這一點。所以現在正是投入額外資金的好時機。再次重申你剛才所說的，我們認為──我們認為目前的估值水準很有吸引力。

Our next question comes from Yatin Suneja from Guggenheim Partners.

下一個問題來自古根漢合夥公司的亞廷·蘇內賈。

Congrats on the quarter. The question is on the lung cancer update that you provided today. I mean if you end up with an identical result to KEYTRUDA in the front-line lung setting, do you compete on anything other than the price? Is that going to be the strategy? Could you maybe comment on the strategy there?

恭喜你本季取得佳績。這個問題是關於您今天提供的肺癌最新情況。我的意思是，如果第一線肺部治療的效果與 KEYTRUDA 完全相同，那麼除了價格之外，你們還能在其他方面競爭嗎？這就是他們的策略嗎？您能否就此策略發表一下看法？

Yes, it's a little early to comment on a strategy till we see the data. I just remind you, this is going to be a very large space. KEYTRUDA is annualizing right now at about, I think, $12 billion. And the whole space is predicted to go much larger than that with most of the sales, at least initially, coming in lung cancer.

是的，在看到數據之前，對策略發表評論還為時過早。我提醒一下，這將是一個非常大的空間。KEYTRUDA目前的年化收入約為120億美元。預計整個市場規模將遠超過這個數字，至少在初期，大部分銷售額將來自肺癌領域。

We have 2 strategies I think that George has been articulating for years. One is we need a foundational strategy so that if it just turns out the only checkpoint inhibitor that continues to make a difference, as it has for the last 5 years in lung cancer, is a PD-1 inhibitor, we want to be there with ours and we want to compete. And we'll see how the data goes.

我認為喬治多年來一直在闡述我們有兩種策略。其一是我們需要一個基礎策略，這樣，如果最終證明唯一能繼續發揮作用的檢查點抑制劑（就像過去 5 年在肺癌領域那樣）是 PD-1 抑制劑，我們希望我們的產品也能參與其中，並與之競爭。我們來看看數據如何。

But it could be one experiment away with either some combination, a co-stim, a bispecific or something else. And then everybody's back, loaded up in the starting gate. So this has been, I think, articulated innumerable times by George: PD-1 is a foundational technology for us in the immuno-oncology space, lung cancer is the biggest opportunity, we want to be there.

但或許只需要一次實驗，嘗試一些組合療法、協同刺激療法、雙特異性療法或其他療法就能成功。然後，所有人都回到了起點，準備就緒。所以，我認為喬治已經無數次闡述過這一點：PD-1 是我們免疫腫瘤學領域的基礎技術，肺癌是最大的機遇，我們希望參與其中。

Our next question comes from Cory Kasimov from JPMorgan.

我們的下一個問題來自摩根大通的科里·卡西莫夫。

This is Matthew on for Cory. So my question is on your BCMA bispecific programs. Can you talk about the differences between REGN5459 and 5458? What informed your decision to advance the former into the clinic? And whether this was in any way dependent on the initial 5458 clinical data.

這是馬修替科里報道。所以我的問題是關於你們的BCMA雙特異性項目。您能談談REGN5459和5458之間的差異嗎？是什麼促使您決定將前者推進臨床應用？以及這是否在某種程度上取決於最初的 5458 例臨床數據。

Yes. I mean, these are all great questions. I think the important point to make is, and it was brought up by a previous caller, that we are really validating our platform and we're excited that it looks like the platform works. And what we're beginning to understand is that one way to control, not only efficacy but also safety, is by the components that are used, particularly the constant components in our platform. I'll remind you, they're all created from entirely natural sequences of antibodies and so forth, so there's no immunogenicity problems.

是的。我的意思是，這些都是很好的問題。我認為需要強調的重點是，正如先前的來電者所提到的，我們正在真正驗證我們的平台，我們很高興看到該平台運作良好。我們逐漸明白，控制療效和安全性的方法之一，就是控制所使用的成分，特別是我們平台中的恆定成分。我提醒你，它們都是由完全天然的抗體序列等製成的，所以不存在免疫原性問題。

And so what we're doing, we committed not based on any data that we saw, but to test a couple of variants of the constant aspects of the platform to try to optimize the efficacy and safety profile. Though obviously we're seeing what look like very competitive profiles right now, we're always aspiring to even do better. So it's just a matter of building and optimizing our platform to maximize the efficacy, the safety equation as best as we can and learn that -- how we can take the platform and generalize it and optimize it to the best. And that's why we're testing, in some cases, at least 2 versions of related bispecifics.

因此，我們所做的，並非基於我們看到的任何數據，而是為了測試平台恆定方面的幾個變體，以嘗試優化其功效和安全性。雖然目前我們看到的競爭非常激烈，但我們始終渴望做得更好。所以，現在的問題在於建立和優化我們的平台，以最大限度地提高療效和安全性，並學習如何推廣和優化該平台，使其達到最佳狀態。因此，在某些情況下，我們會測試至少 2 個相關的雙特異性抗體版本。

So let me just repeat what George said, maybe in my words, is that the platform is powerful, and therefore the activation energy to try more than one thing is low. And so we have that as a competitive advantage.

所以，讓我重複喬治說過的話，也許用我自己的話來說，那就是這個平台很強大，因此嘗試多件事的啟動能量很低。因此，這是我們的競爭優勢。

Thank you. I think we have one more -- time for one more question, Sheryl.

謝謝。我想我們還有一個問題──謝麗爾，最後一個問題。

Our final question comes from Josh Schimmer from Evercore.

最後一個問題來自 Evercore 公司的 Josh Schimmer。

It looks like the sequential quarter-over-quarter growth of DUPIXENT in the third quarter was much lower than it was in the second quarter despite very strong underlying prescription trends. Can you discuss some of the factors underlying that, including potential inventory or gross to net fluctuations or any other factors that might have contributed?

儘管處方趨勢非常強勁，但DUPIXENT第三季的環比成長率似乎遠低於第二季。您能否探討一下造成這種情況的一些潛在因素，包括潛在的庫存波動、毛利與淨利之間的波動，或其他可能導致這種情況發生的因素？

Josh, Marion will take that.

喬什，瑪莉安會接手的。

Sure, happy to. So Josh, we're very pleased with the quarter-on-quarter performance. And as I mentioned in my script, when we just look at, obviously the percentage growth of TRxs quarter-over-quarter, and I believe it was 21%, it was quite substantial. As it relates to gross to net and inventory, I know that inventory is within the normal range and therefore don't have more to report on that area.

當然可以，我很樂意。喬希，我們對本季業績非常滿意。正如我在腳本中提到的，當我們只看 TRxs 的季度環比增長百分比時，顯然是 21%，這是一個相當可觀的增長。關於毛利與淨利和庫存，我知道庫存處於正常範圍內，因此這方面沒有什麼需要報告的。

Great. Thank you, everybody, for joining the call. We'll be around to take questions.

偉大的。謝謝大家參加這次通話。我們會隨時解答疑問。

Thanks a lot.

多謝。

Thank you. Ladies and gentlemen, this concludes our conference for this morning. Thank you for your participation. You may now disconnect.

謝謝。女士們、先生們，我們今天早上的會議到此結束。感謝您的參與。您現在可以斷開連線了。