雷傑納榮製藥 (REGN) 2018 Q4 法說會逐字稿

Welcome to the Regeneron Pharmaceuticals Fourth Quarter 2018 Earnings Conference Call. My name is Paulette, and I will be your operator for today's call. (Operator Instructions) Please note that this conference is being recorded.

歡迎參加 Regeneron Pharmaceuticals 2018 年第四季財報電話會議。我叫寶萊特，我將擔任您今天通話的接線生。（操作員說明）請注意，本次會議正在錄音。

I will now turn the call over to Mark Hudson, Senior Manager, Investor Relations. You may begin.

現在我將把電話轉交給投資者關係高級經理馬克·哈德森。你可以開始了。

Thank you, Paulette. Good morning, and welcome to Regeneron Pharmaceuticals' Fourth Quarter 2018 Conference Call. An archive of this webcast will be available on our website for 30 days under Events.

謝謝你，寶萊特。早安，歡迎參加 Regeneron Pharmaceuticals 2018 年第四季電話會議。本次網路直播的存檔將在我們網站的「活動」欄位下保留 30 天。

Joining me on the call today 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'll open up 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 forecasts and guidance, development programs and related anticipated milestones, collaborations, finances, regulatory matters, intellectual property, pending litigation and competition.

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、智慧財產權、未決訴訟和競爭相關的聲明。

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, or SEC, including its Form 10-K for the year ended December 31, 2018, which we are planning to file with the SEC tomorrow. Regeneron does not undertake any obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise.

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 (SEC) 提交的文件，包括截至 2018 年 12 月 31 日止年度的 10-K 表格，我們計劃明天向 SEC 提交該表格。Regeneron公司不承擔任何公開更新任何前瞻性聲明的義務，無論是由於新資訊、未來事件或其他原因。

In addition, please note that the 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.

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

通話結束後，Bob Landry、Jay Markowitz 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。

Thank you, Mark, and good morning to everyone who has joined us on today's call and webcast.

謝謝馬克，也向今天參加電話會議和網路直播的各位問好。

2018 mark Regeneron's 30th year anniversary. And it was a remarkable year for the company. We are pleased with our pipeline progress, our commercial execution and our financial results. And we remain true to our founding mission of inventing important new medicines for patients in need.

2018年是Regeneron公司成立30週年。對公司而言，這是意義非凡的一年。我們對我們的產品線進展、商業執行和財務業績感到滿意。我們始終秉持創立之初的使命，為有需要的病患研發重要的新藥。

EYLEA, the market-leading anti-VEGF therapy approved across a range of retinal disease, continues to grow. 2018 U.S. net product sales were $4.08 billion, an increase of 10% year-over-year. And 2018 global EYLEA product sales totaled $6.7 billion, an increase of 14% year-over-year.

EYLEA 是市場領先的抗 VEGF 療法，已獲準用於治療多種視網膜疾病，且銷售持續成長。2018 年美國淨產品銷售額為 40.8 億美元，較去年同期成長 10%。2018 年安樂全球產品銷售額總計 67 億美元，較去年同期成長 14%。

We continue to invest in retinal diseases and are pursuing new indications, new formulations and new molecular entities. We have a PDUFA date in May for diabetic retinopathy without diabetic macular edema, or DME, and our submission was based upon our Phase III PANORAMA trial in which we were able to reduce vision-threatening complications of diabetes.

我們將繼續投資於視網膜疾病，並致力於開發新的適應症、新的製劑和新的分子實體。我們針對不伴隨糖尿病性黃斑水腫（DME）的糖尿病視網膜病變，已於 5 月獲得 PDUFA 批准。我們的申請是基於我們的 III 期 PANORAMA 試驗，在該試驗中，我們成功減少了糖尿病的致盲併發症。

In 2018, we made progress fulfilling DUPIXENT's pipeline in a product promised by showing efficacy in additional diseases and patient populations. The clinical data continue to support our scientific hypothesis that DUPIXENT targets the molecular drivers of allergic and atopic diseases.

2018 年，我們在實現 DUPIXENT 產品線目標方面取得了進展，該產品承諾在更多疾病和患者群體中展現療效。臨床數據持續支持我們的科學假設，即 DUPIXENT 靶向過敏性和特異性疾病的分子驅動因素。

In its first approved indication, adult atopic dermatitis, DUPIXENT is now annualizing above $1 billion in net product sales in the United States alone. George and Marion will provide more detail, but let me emphasize that we are still in the early stages of the DUPIXENT opportunity with hopefully many more launches in new diseases, geographies and age groups.

DUPIXENT 的首個核准適應症是成人異位性皮膚炎，目前僅在美國，其年淨銷售額就已超過 10 億美元。George 和 Marion 將提供更多細節，但我想強調的是，我們仍處於 DUPIXENT 機會的早期階段，希望未來能在新的疾病、地區和年齡組中推出更多產品。

Finally, despite the remarkable accomplishments in the nascent field of immuno-oncology, most cancer patients still don't benefit from this approach. We believe that the comprehensive and differentiated strategy that George outlined for you at the JPMorgan Conference is already beginning to deliver on its potential: to bring the hope and promise of immuno-oncology to many more patients.

最後，儘管免疫腫瘤學這一新興領域取得了顯著成就，但大多數癌症患者仍然無法從這種方法中受益。我們相信，喬治在摩根大通會議上向你們概述的全面而差異化的策略已經開始發揮其潛力：為更多患者帶來免疫腫瘤學的希望和前景。

In September 2018, Libtayo became the third FDA-approved PD-1 antibody and the first FDA-approved therapy for the treatment of advanced cutaneous squamous cell carcinoma. In December, at the 2018 American Society of Hematology Annual Meeting, or ASH, we presented new data for Regeneron 1979, our wholly-owned CD20xCD3 bispecific, which we are advancing this year into potentially registrational studies.

2018 年 9 月，Libtayo 成為 FDA 批准的第三種 PD-1 抗體，也是 FDA 批准的第一種用於治療晚期皮膚鱗狀細胞癌的療法。12 月，在 2018 年美國血液學會年會 (ASH) 上，我們展示了 Regeneron 1979 的新數據，這是我們全資擁有的 CD20xCD3 雙特異性抗體，我們今年將推進該抗體進入潛在的註冊研究階段。

We simplified and amended our Immuno-Oncology Discovery Agreement with our collaborator, Sanofi. In the new agreement, we will continue to collaborate on Libtayo as well as our MUC16xCD3 and BCMAxCD3 bispecific antibody programs. For the rest of our immuno-oncology programs, including our co-stimulatory bispecifics, Regeneron retains exclusive rights.

我們簡化並修改了與合作方賽諾菲的免疫腫瘤學發現協議。在新協議中，我們將繼續在 Libtayo 以及我們的 MUC16xCD3 和 BCMAxCD3 雙特異性抗體計畫上合作。對於我們其餘的免疫腫瘤學項目，包括我們的共刺激雙特異性抗體，Regeneron 保留獨家權利。

In summary, in 2018, we continued to build upon the foundation that we established over the last 30 years, which positions us for future continued success as an innovative biotechnology company. And as I said at JPMorgan, after 30 years, all of us at Regeneron feel that we are just getting started.

總而言之，2018 年，我們繼續鞏固了過去 30 年奠定的基礎，這使我們作為一家創新生物技術公司，在未來能夠繼續取得成功。正如我在摩根大通所說，經過 30 年的發展，我們 Regeneron 的所有人都覺得我們才剛起步。

With that, I will now turn the call over to George.

接下來，我將把電話交給喬治。

Thank you, Len, and good morning to everyone. I'd like to begin with our efforts to continue to expand and optimize the benefits provided to patients by EYLEA. As a reminder, in September of 2018, the FDA accepted our supplemental BLA for diabetic retinopathy with an action date of May 13, 2019. This potential label expansion to include patients with diabetic retinopathy without DME, coupled with our existing approval in DME, puts EYLEA on the forefront of treating diabetic eye diseases.

謝謝你，Len，大家早安。首先，我想談談我們為繼續擴大和優化EYLEA為患者帶來的益處所做的努力。提醒一下，2018 年 9 月，FDA 接受了我們針對糖尿病視網膜病變的補充生物製品許可申請 (BLA)，批准日期為 2019 年 5 月 13 日。這項潛在的標籤擴展，將包括不伴有糖尿病性黃斑水腫的糖尿病視網膜病變患者，再加上我們目前在糖尿病性黃斑水腫方面的批准，使 EYLEA 處於治療糖尿病眼病的前沿。

Let me emphasize data from our Phase III PANORAMA study in diabetic retinopathy. In addition to anatomic improvement, we have, for the first time, shown that EYLEA can reduce vision-threatening complications in people who have diabetic retinopathy. Contrary to the perception of some that diabetic retinopathy is a slowly evolving condition, our PANORAMA study demonstrated that patients with moderately severe or severe diabetic retinopathy may progress rapidly, developing vision-threatening complications or new onset DME.

讓我重點介紹一下我們針對糖尿病視網膜病變的 III 期 PANORAMA 研究的數據。除了改善解剖結構外，我們還首次證明，EYLEA 可以減少糖尿病視網膜病變患者的失明併發症。與一些人認為糖尿病視網膜病變是一種緩慢發展的疾病的看法相反，我們的 PANORAMA 研究表明，中度或重度糖尿病視網膜病變患者病情可能會迅速進展，出現威脅視力的併發症或新發糖尿病性黃斑水腫。

With more than 40% of the overall patient population suffering from these events and more than 50% of the patients in the severe category, it's certainly showing the high risk that these patients are under. In the overall patient population, EYLEA reduced these events by more than 75%. In patients with -- in any case, more complete data on the 52-week Phase III PANORAMA study will be presented in the angiogenesis meeting on Saturday and has been submitted to the FDA.

超過 40% 的患者群體遭受這些事件的困擾，超過 50% 的患者屬於重症患者，這無疑表明這些患者面臨很高的風險。在所有患者中，EYLEA 使這些事件減少了 75% 以上。無論如何，關於為期 52 週的 III 期 PANORAMA 研究的更完整數據將於週六在血管生成會議上公佈，並已提交給 FDA。

It is remarkable that despite many attempts to improve upon the efficacy of VEGF blockade for retinal disease, based on the data we have seen, no other mechanism has proven more beneficial and no other drug in head-to-head pivotal trials has shown superior visual acuity outcomes compared to EYLEA. But we aren't standing still. Our goal is to further advance the treatment of retinal diseases.

值得注意的是，儘管人們多次嘗試提高 VEGF 阻斷治療視網膜疾病的療效，但根據我們所看到的數據，沒有其他機制被證明更有益，也沒有其他藥物在頭對頭的關鍵性試驗中顯示出比 EYLEA 更優異的視力結果。但我們並沒有停滯不前。我們的目標是進一步推進視網膜疾病的治療。

Later this year, we will begin clinical development of a higher-dose formulation of aflibercept to determine whether it can safely provide improved efficacy and longer-lasting benefit. In addition, we are actively developing new molecular entities, which we may advance to clinical trials as soon as this year. And we are in the earlier stages of development for gene therapies and other novel approaches.

今年晚些時候，我們將開始對更高劑量的阿柏西普製劑進行臨床開發，以確定它是否能夠安全地提供更好的療效和更持久的益處。此外，我們正在積極開發新的分子實體，最快可能在今年將其推進到臨床試驗階段。我們目前仍處於基因療法和其他創新方法的早期研發階段。

I'd now like to turn to DUPIXENT. Our own clinical studies support decades of basic science suggesting the target of DUPIXENT, that is interleukin-4 and interleukin-13 signaling is a fundamental driver of Type 2 inflammation, common to many allergic or atopic deceases. This scientific insight underlies the basis of why many believe DUPIXENT is a pipeline in a product.

我現在想改用DUPIXENT。我們自己的臨床研究支持了數十年的基礎科學研究，這些研究表明 DUPIXENT 的靶點，即白細胞介素-4 和白細胞介素-13 信號傳導，是 2 型炎症的基本驅動因素，而 2 型炎症是許多過敏性或特應性疾病的常見特徵。這項科學見解是許多人認為 DUPIXENT 是產品研發管線的基礎。

Following our FDA approval for adult atopic dermatitis in 2017 and our approval in asthma at the end of last year, we are anticipating 3 important upcoming regulatory milestones for DUPIXENT. First, a decision by the FDA in adolescent atopic dermatitis with an action date of March 13, 2019. Second, an EMA decision in the first half of the year on asthma in adults and adolescents. And third, potential FDA acceptance of the supplemental BLA for chronic rhinosinusitis with nasal polyposis based on 2 overwhelmingly positive Phase III studies.

繼 2017 年獲得 FDA 批准用於治療成人異位性皮膚炎，以及去年年底獲得 FDA 批准用於治療氣喘之後，我們預計 DUPIXENT 將迎來 3 個重要的監管里程碑。首先，FDA 於 2019 年 3 月 13 日就青少年異位性皮膚炎做出了決定。其次，EMA 將於今年上半年就成人和青少年氣喘問題做出決定。第三，FDA可能會接受針對慢性鼻竇炎伴鼻息肉的補充生物製品許可申請，​​該申請基於兩項結果非常積極的III期研究。

As DUPIXENT potentially expands into adolescents with atopic dermatitis, it is important to remember how serious and devastating this disease can be. The teenage years are hard enough without a debilitating skin condition that may impact self-image, sleep and the ability to concentrate in school. Most of the patients in our trials have the disease covering over half their bodies. And patients have described the accompanying itch as similar to unrelenting poison ivy that never goes away.

隨著 DUPIXENT 可能擴展到患有異位性皮膚炎的青少年，重要的是要記住這種疾病有多嚴重和破壞性。青少年時期本來就充滿挑戰，如果再加上嚴重的皮膚疾病，可能會影響自我形象、睡眠和在學校的注意力，那就更是難上加難了。我們試驗中的大多數患者，其身體一半以上的部位都受到了這種疾病的影響。患者形容伴隨而來的搔癢感類似於揮之不去的毒藤皮疹。

As measured by EASI score, DUPIXENT reduce the extent and severity of skin lesions by an average of 60% to 70%, with significant improvements in other measures including itch. Beyond this potential approval in adolescents, we hope to bring the benefit of DUPIXENT to even younger AD patients. And this year, we expect to report results of the Phase III trial in patients aged 6 to 11 years.

根據 EASI 評分衡量，DUPIXENT 可使皮膚損傷的程度和嚴重程度平均降低 60% 至 70%，其他指標（包括搔癢）也有顯著改善。除了在青少年中獲得潛在批准外，我們希望將 DUPIXENT 的益處帶給更年輕的 AD 患者。今年，我們預計將公佈針對 6 至 11 歲患者的 III 期試驗結果。

Turning to DUPIXENT in asthma. We are anticipating approval in the EU and Japan later this year. The U.S. asthma launch is underway, and it's particularly gratifying to see good early uptake among allergists who have had prior experience using DUPIXENT for patients with atopic dermatitis. You will hear more about the asthma launch from Marion.

氣喘治療轉向使用DUPIXENT。我們預計將於今年稍後獲得歐盟和日本的批准。美國氣喘藥物上市正在進行中，尤其令人欣慰的是，對於先前使用 DUPIXENT 治療異位性皮膚炎患者的過敏症專科醫生來說，該藥物的早期接受度很高。您將從 Marion 那裡聽到更多關於哮喘防治計畫啟動的資訊。

It is widely appreciated for patients with serious allergic diseases. Our trials demonstrate substantial level of co-morbid conditions in individual patients. For example, in our adolescent atopic dermatitis trials, more than 50% had asthma as well and more than 60% to 70% had another allergic condition, such as food allergy or inhaled allergies.

它深受患有嚴重過敏性疾病患者的青睞。我們的試驗表明，個別患者存在相當程度的合併症。例如，在我們針對青少年異位性皮膚炎的試驗中，超過 50% 的患者同時患有氣喘，超過 60% 至 70% 的患者患有其他過敏性疾病，如食物過敏或吸入性過敏。

Many believe that allergic atopic diseases is a systemic condition driven by immune imbalance due to the Type 2 inflammation, which manifests itself to different degrees in different parts of the body in different patients. Consistent with this viewpoint and with our own emerging clinical data, we're exploring multiple potential new allergic or atopic conditions for DUPIXENT. As I mentioned previously, we have a pending supplementary BLA for chronic rhinosinusitis with nasal polyposis.

許多人認為過敏性特異性疾病是一種由 2 型發炎引起的免疫失衡所驅動的全身性疾病，這種疾病在不同患者的身體不同部位表現出的程度也不同。與此觀點以及我們自身不斷湧現的臨床數據一致，我們正在探索 DUPIXENT 的多種潛在的新過敏或特異性疾病。正如我之前提到的，我們有一項針對慢性鼻竇炎伴鼻息肉的補充生物製品許可申請正在審批中。

In addition, we have recently initiated Phase II/III study of dupilumab in patients and adolescents with eosinophilic esophagitis, the Phase II study in collaboration with Aimmune Therapeutics of dupilumab in peanut allergy, and we have completed the enrollment in Phase II study for grass allergy. We will update you in the future about new trials and new indications.

此外，我們最近啟動了度普利尤單抗治療嗜酸性食道炎患者和青少年的 II/III 期研究，與 Aimmune Therapeutics 合作開展了度普利尤單抗治療花生過敏的 II 期研究，並且我們已經完成了度普利尤單抗治療草過敏的 II 期研究的入組。未來我們將向您通報新的試驗和新的適應症。

We view our interleukin-33 program as a potential complement to DUPIXENT. We are studying Regeneron 3500, our interleukin-33 antibody, both as monotherapy as well as in combination with DUPIXENT in several indications, including asthma, atopic dermatitis and COPD. We will report results of the Phase II study in asthma in 2019. Two Phase II studies in atopic dermatitis were recently initiated: an anti-interleukin-33 monotherapy dose response study and a combination study with DUPIXENT. While it is unlikely that interleukin-33 blockade alone will provide the degree of benefit observed with DUPIXENT, our program is designed to capture any potential incremental benefit that may result from the combination.

我們認為我們的白血球介素-33計畫可以作為DUPIXENT的潛在補充。我們正在研究 Regeneron 3500（一種白細胞介素-33 抗體），包括作為單藥療法以及與 DUPIXENT 聯合用於治療多種疾病，包括氣喘、異位性皮膚炎和 COPD。我們將於 2019 年公佈氣喘 II 期研究的結果。最近啟動了兩項針對異位性皮膚炎的 II 期研究：一項抗白介素-33 單藥治療劑量反應研究和一項與 DUPIXENT 聯合用藥的研究。雖然單獨使用白細胞介素-33阻斷不太可能達到DUPIXENT所觀察到的療效，但我們的方案旨在捕捉聯合治療可能帶來的任何潛在額外療效。

Moving on now to our immuno-oncology portfolio. We recently unveiled what we believe is a rational and comprehensive immuno-oncology strategy, with our PD-1 antibody, Libtayo, at its foundation. In September of 2018, Libtayo, the third FDA-approved anti-PD-1, became the first FDA-approved treatment of any kind for advanced cutaneous squamous cell carcinoma, or CSCC. Outside the United States, the European Medicines Agency is reviewing our regulatory application, and we expect a decision later this year.

接下來，我們來看看我們的免疫腫瘤產品組合。我們最近公佈了我們認為合理且全面的免疫腫瘤學策略，該策略以我們的 PD-1 抗體 Libtayo 為基礎。2018 年 9 月，第三種獲得 FDA 批准的抗 PD-1 藥物 Libtayo 成為 FDA 批准的用於治療晚期皮膚鱗狀細胞癌 (CSCC) 的首個藥物。在美國以外，歐洲藥品管理局正在審查我們的監管申請，我們預計今年稍後將做出決定。

To maximize the substantial Libtayo opportunity in dermato-oncology, we will be commencing adjuvant studies in CSCC in the first half of 2019, with new adjuvant studies to follow. And we are studying Libtayo in other skin cancers where we believe it will have a benefit.

為了最大限度地發揮 Libtayo 在皮膚腫瘤學領域的巨大潛力，我們將於 2019 年上半年開始在 CSCC 中進行輔助治療研究，隨後也將進行新的輔助治療研究。我們正在研究 Libtayo 在其他皮膚癌中的應用，我們相信它會對這類皮膚癌有益。

Beyond dermato-oncology, we consider non-small cell lung cancer to be a major new potential indication for Libtayo. Our Phase III program in non-small cell lung cancer is building on the rapidly evolving treatment paradigm. As we stated previously, we have doubled the size of our trial comparing Libtayo monotherapy to chemotherapy in PD-L1-high patients. Regarding combinations, we will be focusing our efforts in first-line treatment and combination therapy of Libtayo with chemotherapy.

除了皮膚腫瘤學之外，我們認為非小細胞肺癌是 Libtayo 的重要的新潛在適應症。我們的非小細胞肺癌 III 期計畫是建立在快速發展的治療模式之上的。正如我們先前所述，我們已將比較 Libtayo 單藥治療與化療在 PD-L1 高表達患者中的療效的試驗規模擴大了一倍。關於合併用藥，我們將重點放在利妥昔單抗與化療的第一線治療和合併治療。

The ongoing Phase III combination study is being amended to enroll non-small cell lung cancer patients irrespective of histology and levels of PD-L1 expression and to randomized them to Libtayo plus chemotherapy or chemotherapy alone. Amazingly enough, despite years of effort in many pivotal trials, there is only 1 PD-1 or PD-L1 antibody approved as monotherapy in first-line metastatic non-small cell lung cancer. If our ongoing trials succeed, we have the potential to be the second.

正在進行的 III 期聯合治療研究正在修改，以招募非小細胞肺癌患者，無論其組織學類型和 PD-L1 表達水平如何，並將他們隨機分配到 Libtayo 聯合化療組或單獨化療組。令人驚訝的是，儘管多年來在許多關鍵試驗中付出了努力，但目前只有 1 種 PD-1 或​​ PD-L1 抗體被批准作為一線轉移性非小細胞肺癌的單藥療法。如果我們正在進行的試驗成功，我們有可能成為第二家。

Unfortunately for patients, even in tumor settings with some response, the majority of patients still do not benefit from PD-1 blockade. Moreover, little benefit has been demonstrated with PD-1 and PD-L1 blockade or any other immunotherapy in many of the most common tumor types, such as prostate, pancreatic, colorectal and breast. This, honestly, is an important area of unmet need.

對患者來說不幸的是，即使在腫瘤治療有一定療效的情況下，大多數患者仍然無法從 PD-1 阻斷治療中獲益。此外，對於前列腺癌、胰腺癌、結直腸癌和乳腺癌等許多最常見的腫瘤類型，PD-1 和 PD-L1 阻斷或任何其他免疫療法都未顯示出太多益處。說實話，這確實是亟待滿足的重要需求領域。

As you heard me say recently, we are excited about our bispecific franchise. And in particular, 2 classes: the CD3 bispecifics and the co-stimulatory bispecifics. We believe that these bispecifics may have important anticancer activity on their own and, in combinations that can include Libtayo, have the potential to extend the benefits of the immunotherapy in both immunoresponsive tumors as well as, thus far, immuno-unresponsive tumor types.

正如我最近所說，我們對我們的雙特異性特許經營權感到非常興奮。具體來說，分為兩類：CD3 雙特異性抗體和共刺激雙特異性抗體。我們相信這些雙特異性抗體本身可能具有重要的抗癌活性，並且與 Libtayo 聯合使用，有可能擴大免疫療法在免疫反應性腫瘤以及迄今為止免疫無反應性腫瘤類型中的益處。

Three of our CD3 bispecifics are already in the clinic, with 1 of them showing impressive initial results as a monotherapy in very advanced late-stage patients. In December of 2018 at ASH, we presented the exciting data for Regeneron 1979, our CD20xCD3 bispecific for B-cell non-Hodgkin lymphoma, or NHL. At doses we are considering for potential pivotal trials, treatment of these patients with relapsed refractory follicular lymphoma resulted in a 100% objective response rate and an 80% complete response rate. 9 out of 10 patients maintained their response during treatment. And the 1 patient that have progressed did so in the setting of prolonged treatment interruption.

我們的三種 CD3 雙特異性抗體已進入臨床治療，其中一種作為單藥療法在晚期患者中顯示出令人印象深刻的初步結果。2018 年 12 月，我們在 ASH 大會上展示了 Regeneron 1979 的令人興奮的數據，這是一種用於治療 B 細胞非何杰金氏淋巴瘤 (NHL) 的 CD20xCD3 雙特異性抗體。在我們考慮用於潛在關鍵性試驗的劑量下，對這些復發難治性濾泡性淋巴瘤患者進行治療，客觀緩解率達到 100%，完全緩解率達到 80%。10名患者中有9名在治療期間保持了療效。而那 1 例病情進展的患者，是在治療中斷時間較長的情況下出現的。

At higher doses, we are also being -- seeing increases in the response rates in the harder-to-treat relapsed refractory diffuse large B-cell lymphoma, or DLBCL, and are approaching the level of response reported with CAR-Ts. Based on our emerging data, in 2019, we're planning to initiate potential pivotal studies with our CD20xCD3 bispecific for third-line follicular lymphoma as well as DLBCL.

在高劑量下，我們也看到，對於更難治療的複發性難治性瀰漫性大B細胞淋巴瘤（DLBCL），反應率有所提高，並且正在接近CAR-T療法所報導的反應水平。根據我們目前掌握的數據，我們計劃在 2019 年啟動針對三線濾泡性淋巴瘤和瀰漫性大B細胞淋巴瘤的 CD20xCD3 雙特異性抗體的潛在關鍵性研究。

Our second CD3 bispecific antibody to enter clinical development targets MUC16 for ovarian cancer. The MUC16 epitope that we target is the remaining mAb of the membrane-bound protein that, when shed, is known as CA125, the well-known biomarker for ovarian cancer.

我們第二款進入臨床開發的 CD3 雙特異性抗體標靶 MUC16，用於治療卵巢癌。我們靶向的 MUC16 抗原決定基是膜結合蛋白的剩餘 mAb，該蛋白脫落後被稱為 CA125，是眾所周知的卵巢癌生物標記。

And our BCMAxCD3 bispecific antibody has just entered clinical development for the treatment of multiple myeloma. We're encouraged by preliminary results of both CAR-T as well as BiTEs targeting BCMA in multiple myeloma and believe that our BCMAxCD3 bispecific has the potential of being an important addition in this new area.

我們的 BCMAxCD3 雙特異性抗體已進入治療多發性骨髓瘤的臨床開發階段。我們對 CAR-T 和 BiTEs 靶向 BCMA 治療多發性骨髓瘤的初步結果感到鼓舞，並相信我們的 BCMAxCD3 雙特異性抗體有可能成為這一新領域的重要補充。

We recently announced that we're introducing to the clinic an entirely new class of bispecifics, which we term co-stimulatory bispecifics. Compelling data in our animal models indicate that this new class of bispecific can enhance the anticancer benefit when combined with our PD-1 antibody as well as with our CD3 class of bispecifics. This year, we will be introducing 2 of these co-stimulatory bispecifics into the clinic.

我們最近宣布，我們將向臨床引入一類全新的雙特異性抗體，我們稱之為共刺激雙特異性抗體。我們的動物模型中的有力數據表明，這種新型雙特異性抗體與我們的 PD-1 抗體以及 CD3 類雙特異性抗體聯合使用時，可以增強抗癌效果。今年，我們將把其中 2 種共刺激雙特異性抗體引入臨床。

We entered the field of immuno-oncology with a long-term and comprehensive vision. We have created a large number of rational combination opportunities, enabled by the mixing and matching of our technology platforms and capabilities. There are settings like advanced cutaneous squamous cell carcinoma for Libtayo and advanced relapsed refractory non-Hodgkin lymphoma for Regeneron 1979, where our antibodies have demonstrated an impressive single-agent activity in clinical trials.

我們以長遠和全面的視角進入了免疫腫瘤學領域。透過對我們技術平台和能力的靈活組合，我們創造了大量合理的組合機會。在某些特定情況下，例如 Libtayo 用於治療晚期皮膚鱗狀細胞癌，以及 Regeneron 1979 用於治療晚期復發難治性非何杰金氏淋巴瘤，我們的抗體在臨床試驗中已顯示出令人印象深刻的單藥活性。

In many other settings, however, monotherapy is unlikely to be enough. This is where our combination strategy comes into play. And to supplement our internal efforts, we have collaborations with companies like bluebird that have therapeutic modalities, potential synergistic with those that we have in-house.

然而，在許多其他情況下，單一療法可能不足以達到目的。這就反映了我們的組合策略的作用。為了補充我們內部的努力，我們與像 bluebird 這樣的公司合作，這些公司擁有與我們內部療法可能產生協同效應的治療方式。

Let me change gears now to fasinumab, our antibody to Nerve Growth Factor or NGF, the chronic pain from osteoarthritis of the hip or knee. I want to highlight 2 key points regarding our ongoing program. First, as we reported in August, fasinumab continue to show good efficacy in our latest Phase III. At week 16, the study met both co-primary endpoints and all key secondary endpoints.

現在讓我換個話題，談談法西單抗，這是我們針對神經生長因子（NGF）的抗體，可以治療髖關節或膝關節骨關節炎引起的慢性疼痛。我想重點強調我們正在進行的專案的兩個關鍵點。首先，正如我們在 8 月報導的那樣，fasinumab 在我們最新的 III 期臨床試驗中繼續顯示出良好的療效。在第 16 週，該研究達到了兩個共同主要終點和所有關鍵次要終點。

We believe that we may have identified the minimally effective dose that may mitigate treatment-associated arthropathies in total joint replacements that have been observed at higher doses and are the major safety concern of this class. With each day that goes by without safety signals stopping the Phase III studies, we are one step closer to bringing this drug to the many people who are now suffering and, sometimes, seek alternative treatments, such as opioids.

我們相信，我們可能已經找到了最小有效劑量，可以減輕全關節置換術中觀察到的與治療相關的關節病，這些關節病是在較高劑量下觀察到的，也是此類藥物的主要安全隱患。隨著 III 期研究持續進行，沒有出現任何安全信號導致研究停止，我們距離將這種藥物帶給眾多正在遭受痛苦、有時不得不尋求替代療法（如阿片類藥物）的人們又近了一步。

I've given you just a few updates about some of the 7 Regeneron-discovered drugs that are now approved and 16 additional drug candidates in our clinical pipeline. We don't have time in our prepared remarks to discuss them all, but we're happy to take questions during the Q&A.

我剛剛只是向大家簡要介紹了 Regeneron 公司研發的 7 種已獲批准的藥物以及我們正在進行臨床研發的 16 種候選藥物。我們準備的發言稿沒有足夠的時間討論所有問題，但我們很樂意在問答環節回答大家的問題。

Before I close, I would like to highlight that the Regeneron Genetics Center has recently sequenced its 500,000th individual. On top of this major accomplishment, our goal is to sequence another 0.5 million people in 2019. These genetic sequences are all linked to detailed electronic medical records. Along with our collaborators, like Geisinger Health Systems and the UK Biobanks, and with funding from our colleagues in the biopharmaceutical industry, we're amassing what may be the world's largest big data human sequencing resource, which is making a significant contribution to our drug discovery and development efforts.

在結束之前，我想先強調一下，Regeneron 遺傳學中心最近完成了第 50 萬個個體的基因定序。除了這項重大成就之外，我們的目標是在 2019 年再對 50 萬人進行基因定序。這些基因序列都與詳細的電子病歷相關聯。我們與蓋辛格醫療系統和英國生物銀行等合作者，以及生物製藥行業的同行們的資助，正在積累可能是世界上最大的大數據人類測序資源，這對我們的藥物發現和開發工作做出了重大貢獻。

With that, I'd like to turn the call over to Marion.

接下來，我想把電話交給瑪莉安。

Thank you, George, and good morning, everyone. I'd like to start with EYLEA. For the fourth quarter, U.S. EYLEA net product sales grew 11% year-over-year to $1.08 billion. And for the full year 2018, U.S. EYLEA sales grew 10% to $4.08 billion. EYLEA sales growth resulted from an increase in demand and not from price. Based on U.S. net product sales, EYLEA continues to be the market leader, with 72% of the overall branded U.S. anti-VEGF market in the fourth quarter.

謝謝你，喬治，大家早安。我想先從愛樂（EYLEA）說起。第四季度，美國安禮製藥淨產品銷售額年增 11%，達到 10.8 億美元。2018 年全年，安禮在美國的銷售額成長了 10%，達到 40.8 億美元。EYLEA的銷售成長是由於需求增加而非價格上漲。根據美國淨產品銷售額，安怡繼續保持市場領先地位，在第四季度佔據美國品牌抗 VEGF 市場 72% 的份額。

We continue to see overall market growth in both wet AMD and DME, driven by the aging population, increase in diabetes prevalence and physician preference for EYLEA. Approximately 90% of patients across all peer segments can access EYLEA as their first line of therapy. Regeneron will continue to stay engaged with stakeholders in order to preserve physician choice and patient access to EYLEA and its significant clinical benefits.

我們看到，在濕性 AMD 和 DME 市場整體成長的推動下，人口老化、糖尿病盛行率上升以及醫生對 EYLEA 的偏好，使得市場持續成長。在所有同齡群體中，約 90% 的患者可以將 EYLEA 作為第一線治療方案。再生元將繼續與利害關係人保持溝通，以維護醫生選擇權和患者獲得 EYLEA 及其顯著臨床益處的權利。

Building on our leadership position in wet AMD and diabetic eye disease, we see a major growth opportunity for EYLEA in diabetic retinopathy without DME. The PDUFA date for this new indication is May 13. As a reminder, of the estimated 3.5 million people in the U.S. for the diabetic retinopathy without DME, approximately 1 million individuals have moderately severe or severe disease and are at greatest risk for progression and loss of vision.

憑藉我們在濕性 AMD 和糖尿病眼部疾病領域的領先地位，我們看到 EYLEA 在非 DME 糖尿病視網膜病變領域擁有巨大的成長機會。此新適應症的PDUFA日期為5月13日。提醒大家，在美國約有 350 萬人患有糖尿病視網膜病變（無 DME），其中約有 100 萬人患有中度至重度疾病，他們面臨病情惡化和視力喪失的最大風險。

We believe the PANORAMA results that George described support early intervention with EYLEA and may help evolve the clinical treatment paradigm. Pending approval of EYLEA in this indication, comprehensive plans are in place to support disease education focused on the benefits of early treatment. We also remain on track to launch EYLEA prefilled syringe in 2019 pending regulatory approval.

我們認為喬治描述的 PANORAMA 結果支持使用 EYLEA 進行早期幹預，並可能有助於發展臨床治療模式。在 EYLEA 獲準用於此適應症之前，已製定了全面的計劃，以支持以早期治療益處為重點的疾病教育。我們仍按計劃在 2019 年推出 EYLEA 預灌封注射器，目前正在等待監管部門的批准。

Turning now to DUPIXENT. Local net product sales in the fourth quarter were $319 million and, in the U.S. alone, reached $259 million, representing 18% quarter-over-quarter growth and 89% year-over-year. Prescriber experience and depth continued to improve, with approximately 14,000 health care providers having prescribed DUPIXENT and over 46,000 patients have received therapy. There is a notable increase in DUPIXENT prescribing trends, with weekly new-to-brand prescriptions, or NBRx, increasing to between 750 and 850 patients per week compared to approximately 500 to 600 per week in earlier quarters.

接下來我們來看看DUPIXENT。第四季本地淨產品銷售額為 3.19 億美元，光在美國就達到 2.59 億美元，季增 18%，年增 89%。處方醫生的經驗和水準持續提高，約有 14,000 名醫療保健提供者開立了 DUPIXENT 處方，超過 46,000 名患者接受了治療。DUPIXENT 的處方趨勢顯著增加，每週新開處方（NBRx）數量增加到每週 750 至 850 名患者，而前幾季度每週新開處方數量約為 500 至 600 名患者。

We attribute our robust fourth quarter performance to patient and physician experience, our overall promotional campaign, field force impact, national branded television advertisement for atopic dermatitis and the asthma launch. On October 19th, the FDA-approved DUPIXENT's second major U.S. indication in moderate to severe asthma in patients aged 12 years and older, with an eosinophilic phenotype or with oral corticosteroid-dependent asthma. We expect a regulatory decision in the EU and Japan in the first half of this year.

我們將第四季度強勁的業績歸功於患者和醫生的體驗、我們整體的推廣活動、銷售團隊的影響、針對異位性皮膚炎的全國品牌電視廣告以及氣喘產品的上市。10 月 19 日，FDA 批准了 DUPIXENT 在美國的第二個主要適應症，即用於治療 12 歲及以上、具有嗜酸性表型或口服皮質類固醇依賴性氣喘的中度至重度氣喘患者。我們預計歐盟和日本將在今年上半年做出監管決定。

3 months into the U.S. asthma launch, we're encouraged by the early uptake in prescriber interest. Our goal is for DUPIXENT to be the preferred first-line biologic for indicated patients with moderate to severe asthma. At this point in the launch, we estimate that over 2/3 of DUPIXENT asthma patients are new to biologics. Allergists and pulmonologists recognize the benefits of DUPIXENT's differentiated clinical profile as the first and only biologic that targets 2 key cytokines central to Type 2 inflammation.

在美國氣喘藥物上市 3 個月後，我們對處方醫師早期表現出的興趣感到鼓舞。我們的目標是使 DUPIXENT 成為中重度氣喘患者的首選第一線生物製劑。在上市初期，我們估計超過 2/3 的 DUPIXENT 氣喘患者是首次使用生物製劑。過敏科醫生和肺科醫生認識到 DUPIXENT 的差異化臨床特性帶來的益處，它是第一個也是唯一一個針對 2 型發炎中 2 個關鍵細胞因子的生物製劑。

DUPIXENT is also differentiated on its efficacy and exacerbations in lung function, established safety profile and flexibility as the only asthma biologic to offer self- or at-home administration. In addition, we would like to emphasize the positive impact of allergists' familiarity with DUPIXENT for their atopic dermatitis patients. Currently, a majority of our prescriptions are coming from this specialty. We look forward to providing insight on the asthma launch in the coming months.

DUPIXENT 的其他優點還包括其對肺功能的療效和緩解作用、已確立的安全特性以及靈活性，它是唯一一種可以自行或在家給藥的氣喘生物製劑。此外，我們也要強調過敏科醫師對 DUPIXENT 的熟悉程度對其異位性皮膚炎患者的正面影響。目前，我們的大部分處方都來自這個專科。我們期待在未來幾個月內為大家帶來更多有關氣喘產品上市的見解。

Additionally, we believe that substantial opportunity remains in atopic dermatitis. To date, despite the impressive market experience that I described, less than 15% of adult AD patients in greatest need have received DUPIXENT therapy. We expect further U.S. growth if the FDA approves DUPIXENT in adolescents ages 12 to 17 on our March 11 PDUFA date. As a reminder, we estimate that the number of potential adolescent patients is about half of the target adult atopic dermatitis population. Further, we expect data from our pediatric study in atopic dermatitis ages 6 to 11 in 2019.

此外，我們認為異位性皮膚炎領域仍有很大的發展機會。儘管我所描述的市場經驗令人印象深刻，但迄今為止，只有不到 15% 的最需要 DUPIXENT 治療的成年 AD 患者接受了治療。如果 FDA 在 3 月 11 日的 PDUFA 日期批准 DUPIXENT 用於 12 至 17 歲的青少年，我們預計美國市場將進一步成長。提醒一下，我們估計潛在的青少年患者人數約為目標成人異位性皮膚炎族群的一半。此外，我們預計將於 2019 年獲得 6 至 11 歲兒童異位性皮膚炎研究的數據。

I'd now like to turn to Libtayo, which was launched in the U.S. on October 1 as the first FDA-approved treatment for patients with metastatic cutaneous squamous cell carcinoma or locally advanced disease who are not candidates for curative surgery or curative radiation. In the EU, we expect a decision later in 2019.

現在我想談談 Libtayo，它於 10 月 1 日在美國上市，是首個獲得 FDA 批准的用於治療轉移性皮膚鱗狀細胞癌或局部晚期疾病患者的藥物，這些患者不適合接受根治性手術或根治性放射治療。歐盟方面，我們預計將在 2019 年稍後做出決定。

In the U.S., fourth quarter net product sales were $15 million, driven by demand. Since launch, we have made in-roads in establishing Libtayo as a standard of care across all lines of therapy in advanced CSCC. Engagement with the medical community remains very positive, especially with medical oncologists and most surgeons. We've quickly established broad market access and the reimbursement coverage for Libtayo, with approximately 95% of total commercial, Medicare and Medicaid lives covered.

在美國，第四季淨產品銷售額為 1500 萬美元，受需求推動。自上市以來，我們已取得進展，使 Libtayo 成為晚期 CSCC 所有治療方案的標準療法。與醫學界的互動仍然非常積極，特別是與腫瘤內科醫生和大多數外科醫生的互動。我們已迅速為 Libtayo 建立了廣泛的市場准入和報銷範圍，涵蓋了約 95% 的商業保險、聯邦醫療保險和聯邦醫療補助計劃參保人群。

We believe that significant opportunities remain to increase Libtayo usage both for first-line and second-line treatment under our approved indication. As a reminder, CSCC is a life-threatening condition responsible for an estimated 7,000 U.S. deaths each year. Based on demographics and enhancements in patient identification referrals, we expect the number of newly diagnosed patients to rise annually.

我們相信，在已核准的適應症範圍內，Libtayo 在第一線和第二線治療中的使用仍有很大的提升空間。提醒大家，CSCC 是一種危及生命的疾病，估計每年在美國造成 7,000 人死亡。根據人口統計和患者識別轉診的改善情況，我們預計每年新確診的患者人數將會增加。

Now to PRALUENT. Global net product sales in the fourth quarter were $93 million, including $60 million in the U.S. In 2018, we made strides to remove access and affordability barriers, and we continued to engage with key stakeholders to drive demand. As a reminder, this market is highly impacted by discounting and contracting, which may affect net sales.

現在來說說 PRALUENT。第四季全球淨產品銷售額為 9,300 萬美元，其中美國銷售額為 6,000 萬美元。 2018 年，我們努力消除取得和負擔能力的障礙，並繼續與主要利害關係人合作，以推動需求。提醒各位，該市場受折扣和合約約束的影響很大，這可能會影響淨銷售額。

As noted last quarter, we have submitted data from the ODYSSEY OUTCOMES trial to regulatory authorities in the EU and in the U.S. Earlier this week, we announced a positive CHMP opinion for the proposed indication in Europe. And in the U.S., the FDA target action date is April 28, 2019.

正如上個季度所指出的，我們已向歐盟和美國的監管機構提交了 ODYSSEY OUTCOMES 試驗的數據。本週早些時候，我們宣布了歐洲藥品管理局 (CHMP) 對該擬議適應症的積極意見。在美國，FDA 的目標行動日期是 2019 年 4 月 28 日。

Moving to KEVZARA. Global net product sales in the fourth quarter were $35 million, including $27 million in the U.S. as demand improved. Within the IL-6 subcutaneous class, KEVZARA now has 38% of dispensed NBRx share and 23% of TRx share. KEVZARA has reimbursement coverage for 98% of U.S. commercial lives, with 79% of patients able to access KEVZARA as either first-line biologic or after failing 1 or 2 other biologic therapies.

搬到 KEVZARA。第四季全球淨產品銷售額為 3,500 萬美元，其中美國銷售額為 2,700 萬美元，原因是需求有所改善。在 IL-6 皮下注射類別中，KEVZARA 目前佔 NBRx 處方份額的 38% 和 TRx 處方份額的 23%。KEVZARA 在美國商業保險覆蓋率達 98%，79% 的患者能夠獲得 KEVZARA 作為第一線生物製劑，或在 1 或 2 種其他生物療法失敗後使用。

I'll now turn the call over to Bob.

現在我將把電話交給鮑伯。

Thank you, Marion, and good morning to everyone on the call today.

謝謝你，瑪麗昂，也祝今天參加電話會議的各位早安。

Regeneron delivered record financial results during the fourth quarter of 2018 and completed a year of strong financial performance. For the fourth quarter, non-GAAP diluted net income per share grew 31% to $6.84 on non-GAAP net income of $786 million. And for the full year, non-GAAP diluted net income per share grew 40% to $22.84 on non-GAAP net income of $2.62 billion.

2018 年第四季度，Regeneron 公司取得了創紀錄的財務業績，並圓滿完成了全年強勁的財務表現。第四季度，非GAAP稀釋後每股淨收益成長31%至6.84美元，非GAAP淨收益為7.86億美元。全年來看，非GAAP稀釋後每股淨收益成長40%至22.84美元，非GAAP淨收益為26.2億美元。

Total revenues were $1.93 billion for the fourth quarter and $6.71 billion for the full year 2018, which represented 22% growth versus fourth quarter 2017 and 14% growth versus full year 2017. For the fourth quarter of 2018, revenue growth continued to be driven by global sales of EYLEA and a significant increase in Sanofi collaboration revenue, due to lower losses from the commercialization of antibodies and the recording of a cumulative catch-up adjustment to revenue, principally due to the amendment of the Immuno-Oncology Discovery and Development Agreement.

2018 年第四季總營收為 19.3 億美元，2018 年全年總營收為 67.1 億美元，分別比 2017 年第四季成長 22% 和比 2017 年全年成長 14%。2018 年第四季度，收入成長繼續由 EYLEA 的全球銷售額和賽諾菲合作收入的大幅增長推動，這主要得益於抗體商業化損失的減少以及收入累計追趕調整的記錄，而累計追趕調整主要是由於免疫腫瘤發現和開發協議的修訂。

For the fourth quarter of 2018, global net product sales of EYLEA were $1.8 billion, an increase of 12% year-over-year. For the full year, global EYLEA net product sales were $6.75 billion, an increase of 14% year-over-year. In our reported U.S. EYLEA results, distributor inventory experienced a slight increase in the fourth quarter of 2018 as compared to the third quarter of 2018, yet remained within our normal 1- to 2-week targeted range.

2018 年第四季度，安樂全球淨產品銷售額為 18 億美元，較去年同期成長 12%。全年來看，安樂全球淨產品銷售額為 67.5 億美元，較去年同期成長 14%。根據我們公佈的美國安樂死業績，2018 年第四季經銷商庫存較 2018 年第三季略有增加，但仍保持在我們正常的 1 至 2 週目標範圍內。

Ex U.S. EYLEA net product sales, recorded by our collaborator, Bayer, were $724 million for the fourth quarter of 2018, representing a 14% reported and an 18% operational or constant-currency basis increase year-over-year. For the full year of 2018, ex U.S. EYLEA net product sales were $2.67 billion and grew 20% on a reported basis and 18% on an operational basis as compared to the full year of 2017.

根據我們的合作夥伴拜耳公司記錄，2018 年第四季安怡（EYLEA）在美國以外的淨產品銷售額為 7.24 億美元，按報告計算年增 14%，按營運或固定匯率計算年增 18%。2018 年全年，除美國以外，EYLEA 的淨產品銷售額為 26.7 億美元，按報告基準計算增長了 20%，按營運基準計算增長了 18%，與 2017 年全年相比。

Total Bayer collaboration revenue for the fourth quarter of 2018 was $302 million, of which $271 million was derived from our share of net profits from EYLEA sales outside the U.S. The $271 million represents year-over-year reported growth of 17% compared to the fourth quarter of 2017. For full year 2018, total Bayer collaboration revenue was $1.08 billion.

2018 年第四季拜耳合作總營收為 3.02 億美元，其中 2.71 億美元來自我們在美國以外地區銷售 EYLEA 產品所獲得的淨利潤份額。與 2017 年第四季相比，這 2.71 億美元年增了 17%。2018 年全年，拜耳合作總營收為 10.8 億美元。

Total Sanofi collaboration revenue was $428 million for the fourth quarter of 2018 and $1.11 billion for the full year of 2018. The increase in Sanofi collaboration revenue in the fourth quarter and full year 2018 versus the prior periods in 2017 was primarily due to increased spend and, thus, reimbursement for Libtayo clinical development activities, lower losses associated with the commercialization of antibodies and the recording of a cumulative catch-up adjustment to revenue of $149 million, primarily in connection with the amendment of the Immuno-Oncology Discovery and Development Agreement.

2018 年第四季度，賽諾菲合作總收入為 4.28 億美元；2018 年全年，合作總收入為 11.1 億美元。2018 年第四季和全年賽諾菲合作收入較 2017 年同期有所增長，主要原因是 Libtayo 臨床開發活動的支出增加，因此報銷額也增加；抗體商業化相關的損失減少；以及累計收入追趕調整 1.49 億美元，這主要是由於免疫腫瘤發現和開發協議的修訂所致。

Under the terms of the Amended Immuno-Oncology Discovery and Development Agreement, Sanofi paid the company $462 million, which included the reimbursement of fourth quarter 2018 Regeneron-incurred research and development costs of $46 million, the prepayment of $120 million for development activities for 2 bispecific programs, BCMAxCD3 and MUC16xCD3, and a termination payment. Revenue associated with the cumulative catch-up is recorded in the other line item of the Sanofi collaboration revenue reported in Table 4 of our press release.

根據修訂後的免疫腫瘤學發現和開發協議的條款，賽諾菲向該公司支付了 4.62 億美元，其中包括報銷 Regeneron 在 2018 年第四季度發生的 4600 萬美元研發費用、預付 1.2 億美元用於 BCMAxCD3 和 MUC16xCD3 這兩個雙特異性項目開發活動，以及一筆特異性項目終止付款。與累計追趕相關的收入已記錄在我們新聞稿表 4 中報告的賽諾菲合作收入的另一項中。

In the fourth quarter of 2018, we recognized a loss of $44 million in connection with the commercialization of products under the antibody license and collaboration agreement with Sanofi, which compares favorably to a loss of $114 million in the fourth quarter of 2017. But as anticipated, this quarter's loss was slightly higher than the $39 million loss from the third quarter of 2018. The lower share loss versus the fourth quarter of 2017 was primarily attributable to higher global net product sales of DUPIXENT and, to a lesser extent, PRALUENT and KEVZARA, continued cost containment for PRALUENT, partly offset by an increase in DUPIXENT commercialization expenses to support the launch in asthma and ongoing global launches in atopic dermatitis.

2018 年第四季度，我們確認了與賽諾菲根據抗體許可和合作協議進行產品商業化相關的 4,400 萬美元虧損，與 2017 年第四季度 1.14 億美元的虧損相比，情況有所好轉。但正如預期的那樣，本季的虧損略高於 2018 年第三季的 3,900 萬美元虧損。與 2017 年第四季相比，市佔率損失減少主要歸因於 DUPIXENT 的全球淨產品銷售額增加，其次是 PRALUENT 和 KEVZARA 的銷售額增加，以及 PRALUENT 成本的持續控制，但部分被 DUPIXENT 商業化費用的增加所抵消，這些費用增加是為了支持其在全球性皮膚炎領域的上市以及在全球性皮膚炎領域的上市以及持續的全球性皮膚炎領域。

As we discussed on our November 2018 earnings conference call, we continue to expect the alliances' financial results to remain variable for the next few quarters as we incur launch expenses for new indications, including a potential label expansion for adolescent patients, aged 12 to 17, with atopic dermatitis and launches into new international markets.

正如我們在 2018 年 11 月的收益電話會議上所討論的那樣，我們預計未來幾個季度聯盟的財務業績仍將波動不定，因為我們將承擔新適應症的上市費用，包括針對 12 至 17 歲患有特應性皮膚炎的青少年患者的潛在標籤擴展以及進軍新的國際市場。

Turning now to expenses. Non-GAAP R&D expenses were $533 million for the fourth quarter of 2018 and $1.96 billion for full year 2018 as compared to $444 million for the fourth quarter of 2017 and $1.78 billion for the full year 2017. The fourth quarter 2018 increase in non-GAAP R&D expense was the result of an increase in Libtayo clinical cost and higher overall R&D headcount and facilities-related costs, partly offset by a decrease in DUPIXENT and PRALUENT development costs.

接下來談談費用。2018 年第四季非 GAAP 研發費用為 5.33 億美元，2018 年全年為 19.6 億美元，而 2017 年第四季為 4.44 億美元，2017 年全年為 17.8 億美元。2018 年第四季非 GAAP 研發費用增加是由於 Libtayo 臨床成本增加以及研發人員總數和設施相關成本增加所致，部分被 DUPIXENT 和 PRALUENT 開發成本的下降所抵消。

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 $347 million for the fourth quarter 2018 compared to $265 million for the fourth quarter 2017. The year-over-year increase was primarily driven by our share of higher immuno-oncology clinical costs and R&D activities associated with the growing number of wholly-owned programs. For year 2018, non-GAAP unreimbursed R&D expense was $1.22 billion. Our press release includes all the information required to calculate unreimbursed non-GAAP R&D expense.

2018 年第四季度，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 3.47 億美元，而 2017 年第四季為 2.65 億美元。年比增幅主要源自於我們承擔的免疫腫瘤臨床成本增加以及與全資擁有的項目數量不斷增長相關的研發活動增加。2018 年，非 GAAP 未報銷研發費用為 12.2 億美元。我們的新聞稿包含了計算未報銷的非GAAP研發費用所需的所有資訊。

For 2019, we are reaffirming our previously provided guidance for non-GAAP unreimbursed R&D to be in the range of $1.59 billion to $1.71 billion. The increase in our 2019 non-GAAP unreimbursed R&D guidance as compared to full year 2018 is primarily attributable to higher clinical trial and manufacturing costs to support Regeneron's wholly-owned programs, including 4 to 6 new molecules expected to be advanced into the clinic in 2019 and the lower Sanofi reimbursement as a result of the Amended Immuno-Oncology Discovery and Development Agreement.

對於 2019 年，我們重申先前提供的非 GAAP 未報銷研發費用的指導意見，即在 15.9 億美元至 17.1 億美元之間。與 2018 年全年相比，我們 2019 年非 GAAP 未報銷研發指導的增加主要歸因於支持 Regeneron 全資擁有的項目（包括預計在 2019 年推進到臨床的 4 至 6 個新分子）的臨床試驗和生產成本增加，以及由於修訂後的免疫腫瘤發現和開發協議導致賽諾菲的報銷減少。

Next, non-GAAP SG&A expense was $411 million for the fourth quarter of 2018 and $1.36 billion for the full year 2018. As noted on our November 2018 earnings call, we realized a higher SG&A spend level in the fourth quarter of 2018 as compared to the first 3 quarters of 2018, primarily due to incremental spend for DUPIXENT, including DTC in the U.S. asthma launch, EYLEA, the launch of Libtayo as well as higher contributions to independent not-for-profit patient-assistance organizations.

其次，2018 年第四季非 GAAP SG&A 費用為 4.11 億美元，2018 年全年為 13.6 億美元。正如我們在 2018 年 11 月的收益電話會議上所指出的，與 2018 年前三個季度相比，我們在 2018 年第四季度實現了更高的銷售、一般及行政費用支出水平，這主要是由於 DUPIXENT 的增量支出（包括在美國的 DTC 哮喘產品上市）、EYLEA、Libtayo 的增量支出（包括在美國上市的 DTC 哮喘產品）、EYLEA、Libta 的捐款性。

We reaffirm our previous 2019 guidance for non-GAAP SG&A expense to be in the range of $1.5 billion to $1.6 billion. The increase in our guidance compared to full year 2018 is primarily driven by increased spend for DUPIXENT, EYLEA and Libtayo. DUPIXENT's increased spend will be focused on the recent U.S. launch of asthma, the expected U.S. launch in atopic dermatitis for adolescent patients and continued support of the atopic dermatitis indication for adults, including DTC. 2019 EYLEA spend increases will be focused on capitalizing on the potential new growth opportunity of EYLEA in diabetic retinopathy without DME, as explained earlier by Marion, and increased patient support programs.

我們重申先前對 2019 年非 GAAP 銷售、一般及行政費用的預期，介於 15 億美元至 16 億美元之間。與 2018 年全年相比，我們業績預期上調的主要原因是 DUPIXENT、EYLEA 和 Libtayo 的支出增加。DUPIXENT 增加的支出將集中用於近期在美國推出的氣喘治療藥物、預計在美國推出的青少年異位性皮膚炎治療藥物，以及繼續支持成人異位性皮膚炎適應症（包括直接面向消費者的治療）。2019 年 EYLEA 支出增加將集中於利用 EYLEA 在非 DME 糖尿病視網膜病變方面的潛在新增長機會（正如 Marion 之前解釋的那樣），以及增加患者支持計劃。

Sanofi reimbursement of Regeneron commercialization-related expenses, a line item found within Sanofi collaboration revenue was $127 million for the fourth quarter of 2018 and $426 million for the full year of 2018. We reaffirm our full year 2019 guidance of Sanofi reimbursement of Regeneron commercialization-related expenses to be in the range of $510 million and $560 million.

賽諾菲向 Regeneron 支付的商業化相關費用（該費用包含在賽諾菲合作收入中）在 2018 年第四季為 1.27 億美元，在 2018 年全年為 4.26 億美元。我們重申 2019 年全年賽諾菲對 Regeneron 商業化相關費用的報銷預期，預計報銷金額在 5.1 億美元至 5.6 億美元之間。

Turning now to taxes. Our effective tax rate was negative 21% and positive 4% for the fourth quarter and full year 2018, respectively, as compared to 69% and 42% for the fourth quarter and full year 2017. The effective tax rate for both the fourth quarter and full year 2018 was positively impacted primarily by the implementation of the Tax Cuts and Jobs Act and the sale of non-inventory-related assets between foreign subsidiaries that was finalized at the end of 2018. Remember, the 2017 effective tax rate was negatively impacted by the enactment of the Tax Cuts and Jobs Act as we had to write-down certain deferred tax assets due to the lower Federal tax rate.

接下來談談稅務問題。2018 年第四季和全年，我們的實際稅率分別為 -21% 和 4%，而 2017 年第四季和全年的實際稅率分別為 69% 和 42%。2018 年第四季和全年的實際稅率主要受到《減稅與就業法案》的實施以及 2018 年底完成的外國子公司之間非庫存相關資產出售的正面影響。請記住，由於聯邦稅率降低，我們不得不對某些遞延所得稅資產進行減記，因此 2017 年的實際稅率受到了《減稅與就業法案》的負面影響。

In the fourth quarter of 2018, we finalized our assessment of the remeasurement of our net deferred tax asset due to the Tax Cuts and Jobs Act and elected to recognize deferred taxes for global intangible low-taxed income, commonly referred to as GILTI. The net tax impact from both the remeasurement of our net deferred tax asset and sale of non-inventory-related assets have been excluded from both fourth quarter and full year 2018 non-GAAP net income, as outlined within Table 3 of our press release.

2018 年第四季度，我們最終確定了因《減稅與就業法案》而重新計量淨遞延所得稅資產的評估，並選擇確認全球無形低稅收入（通常稱為 GILTI）的遞延所得稅。如我們在新聞稿表 3 所述，重新計量遞延所得稅資產淨額和出售非存貨相關資產所產生的淨稅收影響已從 2018 年第四季和全年非 GAAP 淨收入中剔除。

We continue to monitor regulatory guidance under the Tax Cuts and Jobs Act and changes in the global tax environment and will respond as appropriate to ensure our tax strategies are sufficient and aligned with our business operations. We are reaffirming our 2019 guidance for our effective tax rate to be in the range of 14% to 16%, but want to remind you that, as in prior years, we will have volatility from quarter-to-quarter in our tax rate due to the timing of deductions for stock-based compensation.

我們將繼續關注《減稅與就業法案》下的監管指導和全球稅收環境的變化，並酌情做出反應，以確保我們的稅務策略充分且與我們的業務運作一致。我們重申 2019 年的有效稅率預期在 14% 至 16% 之間，但要提醒您，與往年一樣，由於股票選擇權激勵扣除的時間安排，我們的稅率將出現季度波動。

Turning next to cash flow and the December 31, 2018 balance sheet. Regeneron ended the fourth quarter of 2018 with cash and marketable securities of $4.6 billion. And generated free cash flow in excess of $1.8 billion for full year 2018. We calculate free cash flow as the net cash provided by operating activities less capital expenditures. Our capital expenditures for the full year 2018 were $383 million. We are reaffirming our previous 2019 capital expenditure guidance of between $410 million and $490 million.

接下來來看現金流和 2018 年 12 月 31 日的資產負債表。截至 2018 年第四季末，Regeneron 公司持有現金及有價證券 46 億美元。2018 年全年自由現金流超過 18 億美元。我們將自由現金流計算為經營活動產生的現金淨額減去資本支出。2018 年全年，我們的資本支出為 3.83 億美元。我們重申先前對 2019 年資本支出的預期，即 4.1 億美元至 4.9 億美元。

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

那麼，我想把電話轉回馬克。

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

謝謝你，鮑伯。我們的發言稿到此結束。現在我們想開放問答環節。

(Operator Instructions) And our first question comes from Ying Huang from Bank of America Merrill Lynch.

（操作員說明）我們的第一個問題來自美國銀行美林證券的黃穎。

The first question on EYLEA. Obviously, you're waiting for FDA approval in diabetic retinopathy. Can you tell us whether you do think that's going to be a significant growth driver for 2019? Or do you think we should EYLEA -- or we should expect EYLEA to grow at the market growth rate? And then maybe you can comment on the net pricing trend in 2019 for EYLEA as well. Secondly, can you talk about DUPIXENT outlook? Do you believe the asthma indication will start to be a more important growth driver versus atopic dermatitis for 2019?

關於愛力（EYLEA）的第一個問題。顯然，你們正在等待FDA批准該藥物用於治療糖尿病視網膜病變。您認為這是否會成為 2019 年的重要成長動力？還是您認為我們應該預期EYLEA以市場成長率成長？然後，您或許也可以談談安怡在 2019 年的淨定價趨勢。其次，您能談談DUPIXENT的發展前景嗎？您認為到 2019 年，氣喘適應症會比特應性皮膚炎成為更重要的成長驅動因素嗎？

Okay. So thanks for the questions, Ying. On the issue of whether or not diabetic retinopathy is going to be a growth driver in 2019, I think that we'll be in the early stages of the launch for that indication. It's going to take a lot of patient education because it's a paradigm shift. So we don't give guidance, but from a general point of view, I think it's going to take some time to develop that market. Pricing trends, I'm not sure what you're getting at, whether you're talking about external forces or not. But our price has been marked, very modestly impacted to the negative side based upon a slight discount that was provided across the board in 2018. And in terms of asthma, Marion?

好的。謝謝你的提問，穎。關於糖尿病視網膜病變是否會成為 2019 年的成長驅動因素，我認為我們目前仍處於該適應症推出的早期階段。這需要大量的病患教育，因為這是一種範式轉移。所以我們不提供指導，但從總體上看，我認為發展這個市場需要一些時間。關於價格趨勢，我不確定你想表達什麼，你指的是外在因素還是其他因素。但由於 2018 年全面提供的輕微折扣，我們的價格受到了非常輕微的負面影響。那麼，瑪莉昂，你的氣喘情況如何呢？

Yes, I'm happy to comment on asthma. So I gave you some information today on what is very early in the launch and favorable indicators. As I look to your question though in asthma growth opportunities for the future, we do see that as very important. It's not the only DUPIXENT growth driver, I also described the atopic dermatitis growth opportunity in adults and with FDA approval potentially with the adolescents this year. But back to your question on asthma, what's most interesting in these early stages of launch is the response that we're hearing from both allergists and pulmonologists to the differentiating profile of DUPIXENT. Both in terms of its clinical efficacy, the established safety profile and then also there's a very, very important factor of patients being able to self-administer or at-home administer. That, coupled with the fact that for some of these physicians, they're treating patients that have co-morbidities, such as when other Type 2 diseases occur with asthma. So again, it's very early days, but we feel good about the early launch. And I look forward to giving updates in the future. I'll also remind you just in terms of size of patient population for asthma biologics, it's about 1 million patients. But to date, only about 100,000 patients have been treated, eligible asthma patients with biologics. So it is a market with tremendous opportunity.

是的，我很樂意就氣喘問題發表評論。今天我給大家提供了一些關於產品發布初期階段和有利指標的資訊。不過，就您提出的關於氣喘未來發展機會的問題而言，我們認為這非常重要。這並非 DUPIXENT 唯一的成長驅動因素，我還描述了成人異位性皮膚炎的成長機會，並且隨著 FDA 今年可能批准用於治療青少年。但回到你關於氣喘的問題，在上市初期最有趣的是，我們從過敏症專家和肺科醫生那裡聽到了對 DUPIXENT 差異化特性的反饋。無論是從臨床療效、已建立的安全特性來看，或是從病人能夠自行給藥或在家給藥的角度來看，都是一個非常重要的因素。此外，還有一些醫生正在治療患有合併症的患者，例如氣喘合併其他 2 型疾病。所以，現在還處於非常早期的階段，但我們對提前發布感到滿意。我期待未來能為大家帶來最新消息。我還要提醒大家，就氣喘生物製劑的患者群體規模而言，大約有 100 萬名患者。但迄今為止，只有大約 10 萬名符合條件的氣喘患者接受了生物製劑治療。所以這是一個充滿巨大機會的市場。

I'd like to just add to Len's point in response to the contribution of diabetic retinopathy to the market opportunity. I don't want to address the market opportunity specifically, but very importantly, about whether this should really be paradigm shifting and whether or not there should really be a new way of treating patients. And I think that looking at the data, physicians are going to have to make their decisions. But there's a lot of very important outcomes from our study. Number one is, I already mentioned, that the rate of vision-threatening complications and progression in people who have moderate and particularly severe non-proliferative diabetic retinopathy is, I think, much higher than most people thought. Once people progress, treatment, at that point, we know, is probably not going to be as good as prevention. And I think it's a very important question to now ask in terms of the physicians in the entire community, "Should we be working harder to prevent onset of disease and loss of vision that you may never get back?" And in this particular case, "Is a little bit of prevention really worthwhile for the so many patients who are in such high risk?" And I think that, that's something that the community, I'm sure, is going to be debating strongly, especially when all this data is -- comes out and is digested and is discussed.

關於糖尿病視網膜病變對市場機會的貢獻，我想補充 Len 的觀點。我不想具體討論市場機會，但非常重要的一點是，這是否真的應該帶來範式轉變，以及是否真的應該有一種新的病人治療方法。我認為，醫生需要根據這些數據做出決定。但我們的研究得出了許多非常重要的結論。第一點，我已經提到過，中度及重度非增殖性糖尿病視網膜病變患者出現威脅視力的併發症和病情進展的速度，我認為比大多數人想像的要高得多。一旦病情發展到一定程度，我們知道，那時的治療效果可能不如預防。我認為現在對於整個醫療界的醫生來說，這是一個非常重要的問題：「我們是否應該更加努力地預防疾病的發生和視力喪失，以免患者失去可能永遠無法恢復的視力？」 就目前的情況而言，「對於這麼多高危患者來說，哪怕是一點點的預防措施真的值得嗎？」就目前的情況而言，「對於這麼多高危險群患者來說，哪怕是一點點的預防措施真的值得嗎？」我相信，這肯定會成為整個話題和討論問題。

Our next question comes from Chris Raymond from Piper Jaffray.

我們的下一個問題來自Piper Jaffray公司的Chris Raymond。

Just to -- maybe a couple of pipeline questions. So first, just on the CD28 co-stimulatory bispecifics. IgG antibodies have had some challenges, I guess, in the solid tumor setting due to the physiologic and physical properties of these tumors. So your bispecifics maintain an IgG-like structure. I guess, can you maybe talk about some of the properties of these antibodies that may allow for better tumor penetration? And are you going to be maybe a little bit more descriptive of that as we get into the clinic with these 2? And then also maybe on your C5 antibody, 3918. I think in your press release, you talked about initiating a Phase II trial in PNH. But Len, I think I heard you say last month in San Francisco that enrolling a switching study for eculizumab might be a challenge. So maybe any color there as to the plans? Is this targeted at new patients? Or is there some other strategy? And maybe if there's some other complement-mediated disease that may make sense as well?

只是想問幾個關於管道方面的問題。首先，我們只討論 CD28 共刺激雙特異性抗體。我想，由於實體腫瘤的生理和物理特性，IgG 抗體在實體腫瘤治療中遇到了一些挑戰。所以你的雙特異性抗體保持著類似IgG的結構。我想，您能否談談這些抗體的一些特性，這些特性可能有助於更好地穿透腫瘤？那麼，當我們和這兩位患者一起進入診所時，您能否更詳細地描述一下情況呢？然後也可能與你的 C5 抗體有關，3918。我認為您在新聞稿中提到了啟動 PNH 的 II 期試驗。但 Len，我想我上個月在舊金山聽到你說過，招募參與依庫珠單抗轉換研究的患者可能是一個挑戰。所以，關於這些計劃，有什麼線索嗎？這是針對新患者的嗎？或是有其他策略嗎？或許還有其他補體介導的疾病，這也能解釋得通？

So it's a highly competitive space. So we're not going to get too much into our thinking on C5. But as we get down the road, I think our strategy will emerge. I'm going to let George, of course, deal with the CD28 question.

所以這是一個競爭非常激烈的領域。所以我們不會過度討論C5的問題。但隨著時間的推移，我認為我們的策略將會逐漸明朗。當然，我會讓喬治來處理 CD28 的問題。

Yes. I think there's a whole field of pseudoscience that somehow seems to think that the problem with getting responses in solid tumors has something to do with antibodies not having access. Actually, if one really looks carefully and objectively at all the data, if anything, there is better access to the tumor where your blood vessels become actually more permeable and leaky and the levels of natural antibodies as well as administering antibodies is actually much higher in those settings. So that has nothing to do with our strategy or our approach. Our belief, and I think that the overwhelming science, argues that the lack of response to this has much more to do with very specific immune recognition issues. And that's exactly what our co-stims do. They add another level of activation specifically targeted against the tumor, which will add to the immunotherapy benefits of either, for example, checkpoint inhibitors such as PD-1 or the more conventional CD3 like bispecifics. So it's all about properly manipulating the immune environment to attack the tumor. And the problems have really nothing to do with antibody access and whether you're using a full-length antibody or something that's smaller. And certainly, all you have to do to understand that is look at the performance of our CD3 bispecific compared to, for example, smaller BiTEs. And that, I think -- cross-study even shows that the activities are really not at all limited by the size of the reagent. And that's about it.

是的。我認為偽科學領域存在一種觀點，認為實體腫瘤治療效果不佳的問題與抗體無法進入腫瘤組織有關。事實上，如果仔細客觀地觀察所有數據，就會發現，在腫瘤部位更容易接觸到血管，血管的通透性和滲漏性也會增強，天然抗體的水平以及抗體的給藥量也會更高。所以這與我們的戰略或方法無關。我們相信，而且我認為絕大多數科學研究也表明，對此缺乏反應與非常具體的免疫識別問題密切相關。而這正是我們的輔助刺激所做的事。它們增加了針對腫瘤的另一種活化水平，這將增強免疫療法的益處，例如，PD-1 等檢查點抑制劑或更傳統的 CD3 樣雙特異性抗體。所以關鍵在於正確操控免疫環境來攻擊腫瘤。而這些問題其實與抗體取得以及你使用的是全長抗體還是較小的抗體無關。當然，你只需要看看我們的 CD3 雙特異性抗體與例如較小的 BiTE 相比的性能，就能明白這一點。而且，我認為——交叉研究甚至表明，活性實際上根本不受試劑大小的限制。差不多就是這樣了。

In the interest of time, I'd just want to -- as a reminder, to ensure that we get to as many people as possible, if you could just limit the Q&A to 1 question at this time.

為了節省時間，我只想提醒一下，為了確保我們能照顧到盡可能多的人，請您這次將問答環節限制為 1 個問題。

Our next question comes from Geoffrey Porges from SVB Leerink.

我們的下一個問題來自SVB Leerink的Geoffrey Porges。

Congratulations both on the results and in not being mentioned in the safety union last night. I wonder if we could talk a little bit about the cadence through the year, Bob. Your revenue and income statement is notoriously hard to model. And you did have quite a few onetime items, nonrecurring items in Q4. Could you give us a sense of how we should be thinking about collaboration revenue through the year? And whether we should expect there to be a step down in revenue in Q1, which is what we've heard of -- about from many of your peers? Can you also comment about the cadence of expenses through the year, just so we can try and get our models a little bit more in line with your outlook?

恭喜你取得好成績，也恭喜你昨晚在安全工會會議上沒有被提及。鮑勃，我想我們能不能稍微談談這一年的節奏？眾所周知，收入和損益表很難建模。第四季確實有不少一次性項目和非經常性項目。您能否大致介紹一下我們該如何看待全年的合作收入？我們是否應該預期第一季的營收會下降？我們從很多同行那裡都聽到了類似的消息。您能否也談談全年的支出節奏，以便我們能夠調整模型，使其更符合您的預期？

Yes. Geoff, as you know, I mean, we don't get into that much specifics with regards to the quarterly division on expenses and on revenue. I will say, which may not be so evident, with regards to the fourth quarter for Sanofi 2018, right, I mean, we did call out the catch-up adjustment that we're talking about with -- as a result of amending the I/O Discovery Agreement. So I think that, that's clear. But what I also think didn't get caught during the year is that we did terminate the I/O -- sorry, the Antibody Discovery Agreement at the end of 2017. So for each of my quarters in 2018, as it pertains to Sanofi, I was going up against the 2017 run rate that included $130 million of the Antibody Discovery Agreement that I will not have to go up against in 2019. So when people saw the fourth quarter, sure, the onetime catch-up adjustment was significant, but also I didn't go up against the 2017 fourth quarter Sanofi develop -- antibody development because it had been exhausted by the third quarter of 2017. So again, a lot of maturations with regards to that. I don't see anything special with regards to how we would break out expenses throughout the year. I mean, we don't have that much seasonal impact. I have been reading the comments that you've said amongst our peers. I do not express to have the kind of the same inkling that you've heard from them and that's what -- that's been put out to the street on it.

是的。傑夫，你知道的，我的意思是，我們不會詳細討論季度支出和收入的具體情況。我想說的是，這可能不太明顯，關於賽諾菲 2018 年第四季度的情況，對吧，我的意思是，我們確實提到了我們正在討論的追趕調整——這是由於修改了 I/O Discovery 協議而導致的。所以我覺得這一點很清楚。但我認為今年沒有被發現的一點是，我們在 2017 年底終止了 I/O——抱歉，是抗體發現協議。因此，就我 2018 年的每個季度而言，就賽諾菲而言，我都要與 2017 年的業績水平作鬥爭，其中包括 1.3 億美元的抗體發現協議，而我在 2019 年就不必再與此作鬥爭了。所以當人們看到第四季時，當然，一次性的追趕調整意義重大，但我也沒有與 2017 年第四季賽諾菲的抗體研發成果進行比較，因為到 2017 年第三季度，這部分成果已經耗盡。所以，在這方面，還有很多需要改進的地方。我認為在全年費用明細方面沒有什麼特別之處。我的意思是，我們受到的季節性影響並不大。我一直在閱讀您在同行中發表的評論。我並不像你從他們那裡聽到的那樣有所察覺，而那些消息已經傳開了。

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。

The first. Len, is I was just wondering now that the comment period has closed, it would be great to hear your latest thoughts on the Part B demonstration project, if you think the final version will include a provision for EU reference pricing. And if you can't answer that, I would love to hear about insight on the Libtayo launch. Maybe just talk a little bit about, more about the kind of breadth of prescribing. How many of your targeted accounts are already prescribing? Where can that go over the course of the year?

第一個。Len，現在評論期已經結束了，我想問你對 B 部分示範項目的最新想法，你是否認為最終版本會包含歐盟參考定價條款。如果你無法回答這個問題，我很想聽聽你對 Libtayo 發表會的看法。或許可以稍微談談處方範圍之類的問題。您的目標客戶中有多少人已經開始開處方？一年下來，這些錢會流向哪裡？

So I'll let Marion comment in a minute on Libtayo, and we'll give you your 2 questions since you guys are so convicted on your opinions about us. We will anticipate something has got to give regarding the international reference pricing situation because the public, the administration, myself personally and a lot of people in the industry, I think, feel and Americans in general feel it's a bit unfair for America to produce all the drugs through its research and development ecosystem and finance it through its financial marketplace and then pay for it for its consumers and then have a very well-healed European companies get those drugs at a much lower price. The trouble is figuring out a system that can really balance that. And as I've said before, when you have biotechnology companies who have given away the European rights, there is no way to connect those 2 pricing. You can open it up all you want, but you have different people making pricing decisions. So I think the administration does get that. To the extent that this will force people to give them, as I said before, courage, we'll see. Our sense is there's a little bit of opposition to the way this has been proposed on the hill, but we have to see how it all come washes out. Marion, on the Libtayo launch?

所以我會等一會兒讓 Marion 對 Libtayo 發表意見，既然你們對我們抱持如此堅定的看法，我們就把你們的兩個問題拋給你們。我們預期國際參考定價機制必須有所改變，因為公眾、政府、我個人以及業內許多人都認為，美國民眾普遍認為，美國透過其研發體系生產所有藥物，並透過其金融市場為其提供資金，然後由美國消費者支付，而財力雄厚的歐洲公司卻能以低得多的價格獲得這些藥物，這有點不公平。問題在於如何找到一個真正能夠平衡這兩者的系統。正如我之前所說，當生技公司放棄了歐洲的權利時，就無法將這兩種定價連結起來。你可以隨意公開定價，但最終是由不同的人來做定價決定的。所以我覺得政府確實明白這一點。至於這能否像我之前說的那樣，迫使人們鼓起勇氣，我們拭目以待。我們感覺到國會山莊對這項提議的方式有些反對，但我們還得看看最終結果如何。Marion，關於Libtayo的發布？

Sure, happy to comment on the Libtayo launch. First and foremost, incredibly important because Libtayo is the first product with the approval that I mentioned earlier this morning on 4 CSCC patients with metastatic and advanced disease, where previously, they didn't have a treatment therapy. So we've had great interest. To your question on the targets of our activities, we've certainly seen uptake in an appropriate way, albeit early in the launch from some of the most prestigious academic centers, and we see that on a geographic basis across the country. Similarly, we're also seeing uptake secondarily in more community and large hospital settings that have sophisticated oncology and also, in some instances, most surgeons in their practice. I'd also comment that as we look very carefully at the launch, I reported today on 15 million ex factory sales, I mentioned that it is demand-driven. This is not a product with a lot of inventory building. And what we are seeing is that each month we're showing progress in terms of demand for Libtayo. So early days, we're pleased. The payor and access coverage, as I mentioned, went quickly and was very well managed by our team. So we feel very good about the launch of Libtayo. We're working very hard on it.

當然，我很樂意對Libtayo的發布發表評論。首先，Libtayo 非常重要，因為它是第一個獲得批准的產品，正如我今天早上提到的，它可用於治療 4 名患有轉移性和晚期 CSCC 的患者，而此前他們沒有治療方法。所以，我們收到了很多關注。關於您提出的我們活動的目標群體的問題，我們確實已經看到一些最負盛名的學術中心以適當的方式接受了我們的活動，儘管這些活動是在啟動初期進行的，而且我們在全國各地都看到了這種地域性的接受度。同樣，我們也看到，在擁有先進腫瘤學的社區和大型醫院環境中，以及在某些情況下，大多數外科醫生在其執業過程中，這種療法也得到了進一步的推廣。我還要補充一點，當我們仔細審視這次發佈時，我今天報告了1500萬的出廠銷量，我提到這是由需求驅動的。這款產品不需要大量囤貨。我們看到的是，每個月Libtayo的需求都在增加。目前還處於早期階段，但我們很滿意。正如我之前提到的，付款人和准入保障的辦理速度很快，而且我們的團隊管理得非常好。所以我們對Libtayo的發布感到非常滿意。我們正在為此付出巨大的努力。

Everybody has their own metrics, Terence, for how a launch is going. The one that I use is when an oncologist calls us up and tells us that he had a gentleman who had cutaneous squamous cell carcinoma, had exhausted all possible treatments, including multiple rounds of surgery, maximum radiation therapy, other types of target and chemotherapy, and was in the midst of a discussion and headed for hospice because the tumor had invaded from the skin, deep into his jaw and then to the base of his skull. He wasn't able to eat, let alone smile. Heading for hospice, 2 days after the drug was approved, this oncologist had heard about our drug in a podcast, convinced the patient to try it. And 6 weeks later, the patient was home for the holidays with a big smile on his face. Those are the sorts of anecdotes that tell us that this launch is making a difference and will go pretty well.

特倫斯，每個人對產品發布成功與否都有自己的一套衡量標準。我經常使用一個例子：一位腫瘤科醫生打電話告訴我們，他接診了一位患有皮膚鱗狀細胞癌的病人，這位病人已經嘗試了所有可能的治療方法，包括多次手術、最大程度的放射治療、其他類型的標靶治療和化療，醫生正在討論是否要將他送進臨終關懷中心，因為腫瘤已經從皮膚侵入到下頜深處，然後又侵入到下頜底，然後又侵入到下頜深處。他吃不下東西，更別說笑了。這位腫瘤科醫生在藥物獲批兩天后，在病人即將進入臨終關懷階段時，透過播客了解了我們的藥物，並說服病人嘗試使用。6週後，病人帶著燦爛的笑容回家過節了。這些軼事表明，此次發布正在產生影響，而且將會非常成功。

Our next question comes from Carter Gould from UBS.

我們的下一個問題來自瑞銀集團的卡特古爾德。

I have a question, I guess, for George or Len. On the -- on your CD20xCD3, I just wanted to kind of get your latest thoughts on dosing, and specifically, if you've nailed down the go forward doses with those pivotal studies. I recognize you're probably not going to give us those doses on this call, but just if you've nailed those down internally and/or you're still waiting on some of the higher-dose data?

我想問喬治或倫一個問題。關於您的 CD20xCD3，我只是想了解您對劑量方面的最新想法，特別是，您是否已經透過那些關鍵研究確定了後續劑量。我知道你可能不會在這次電話會議上告訴我們這些劑量，但是如果你內部已經確定了這些劑量，或者你還在等待一些更高劑量的數據？

Well, I think, as we've indicated and as we've shown in our presentations, in follicular lymphoma, the results are so impressive, we certainly think we're in the right dose range. And with the DLBCL, we are now getting the sort of activities that are starting to approach what one might be seeing with CAR-T-type therapies and so forth. So we certainly think we're in the right sort of dose range. And as we've said, we anticipate being able to start pivotal studies in both of those settings this year.

嗯，我認為，正如我們已經指出並在我們的演示中展示的那樣，在濾泡性淋巴瘤方面，結果令人印象深刻，我們當然認為我們處於正確的劑量範圍內。對於瀰漫性大B細胞淋巴瘤（DLBCL），我們現在正在進行一些活動，這些活動開始接近CAR-T療法等療法的效果。所以我們認為我們目前的劑量範圍是適當的。正如我們所說，我們預計今年能夠在這兩個領域啟動關鍵性研究。

Our next question comes from Geoff Meacham from Barclays.

下一個問題來自巴克萊銀行的傑夫·米查姆。

Bigger picture question. So Libtayo opens up a new therapeutic area for you guys, but I wanted to ask you about the broader I/O strategy. If rational combos are the main basis, how much of an emphasis does Regeneron place on novel MOAs or targets versus evaluating targets, let's say, pharma or others have explored? I'm just trying to get a sense for differentiation in the oncology strategy.

從更宏觀的角度來看這個問題。所以 Libtayo 為你們開闢了一個新的治療領域，但我想問你們更廣泛的 I/O 策略。如果理性組合是主要基礎，那麼 Regeneron 對新型作用機製或標靶的重視程度，與評估其他製藥公司或機構已經探索過的標靶相比，究竟有多大程度的重視？我只是想了解腫瘤治療策略的差異化之處。

Well, I think that it's a mix, of course. But as you can see from our whole new class of bispecifics, the CD28s, we, I think, are leading a whole new approach that will allow for an entirely new group of combination opportunities. And particularly, as we've tried to explain, the opportunity now activate immune responses and activate the ability of checkpoint inhibitors, like the PD-1s, to actually help in cancers that historically have not been viewed as immunoresponsive, which is as you know the vast majority of them. So we believe, and I think a lot of other people now believe, that we have one of the most innovative and leading-edge approaches to combination opportunities and that certainly having Libtayo as our foundation approach is only going to help these novel approaches try to extend the benefit to many more patients in need.

嗯，我覺得這當然是兩者兼具。但正如您從我們全新的雙特異性抗體 CD28 中看到的那樣，我認為我們正在引領一種全新的方法，這將帶來一系列全新的組合機會。特別是，正如我們試圖解釋的那樣，現在有機會激活免疫反應，並激活檢查點抑製劑（如 PD-1）的能力，從而真正幫助治療歷史上不被認為是免疫反應性的癌症，而眾所周知，這佔了癌症的絕大多數。因此我們相信，而且我認為現在很多人也相信，我們擁有最具創新性和領先性的聯合治療方案之一，而且以 Libtayo 作為我們的基礎方案，肯定有助於這些新方法將益處擴展到更多有需要的患者。

And I would add to that, Geoff, that having multiple approaches, such as an approved PD-1, the CD20, CD3, the co-stims that George mentioned and all the others, even some that others may have, under 1 umbrella, 1 program, I think is very powerful and efficient way to be able to move forward.

傑夫，我還要補充一點，將多種方法，例如已獲批准的 PD-1、CD20、CD3、喬治提到的輔助刺激療法以及所有其他療法（甚至包括其他人可能擁有的療法），整合到一個框架、一個方案中，我認為這是一種非常強大和高效的方式，能夠推動治療進展。

Our next question comes from Cory Kasimov from JPMorgan.

下一個問題來自摩根大通的科里·卡西莫夫。

I wanted to ask you about DUPIXENT and on the asthma side of things. Curious how you're thinking about kind of future biologic penetration in both the moderate and severe asthma patients, kind of subpopulations with the entrance of DUPI and other biologics. I mean, to date, it's obviously been pretty modest for other biologics even in the severe setting. So I'm curious how you see that changing over time.

我想問您關於DUPIXENT以及它在哮喘治療方面的問題。很好奇您如何看待未來生物製劑在中度和重度氣喘患者中的滲透情況，以及隨著杜普利和其他生物製劑的出現，生物製劑在不同亞群中的發展前景。我的意思是，迄今為止，即使在嚴重的情況下，其他生物製劑的療效也明顯相當有限。所以我很想知道您認為這種情況會隨著時間推移而發生怎樣的變化。

So our label, Cory, as you know, includes both moderate and severe patients. It's not unusual that early in a launch, we'll probably tend to get some of the tougher patients. As I mentioned we skew a little bit more towards biologic-naive patients than switches at this point that have heard discussions of both and see evidence and the data of both. But on -- I think we'll have to give it a little bit more time, so I can give you a more robust answer on patient types and uptake of the launch. But certainly, we think the product profile that I've reviewed, in summary, the efficacy, the safety, the ease-of-use and the interest of the 2 major prescribing audiences of allergists and pulmonologists suggest that we have an important indication and a significant opportunity ahead.

所以，科里，正如你所知，我們的標籤涵蓋了中度和重度患者。在產品上市初期，我們遇到一些比較難纏的患者並不罕見。正如我之前提到的，目前我們更傾向於那些從未接受過生物製劑治療的患者，而不是那些已經聽說過這兩種療法的討論，並且看到了這兩種療法的證據和數據，並正在考慮轉用生物製劑的患者。但是——我認為我們需要再給它一點時間，這樣我才能就患者類型和產品上市接受度給出更確切的答案。但可以肯定的是，根據我審查過的產品概況，總而言之，其療效、安全性、易用性以及過敏科醫生和肺科醫生這兩大主要處方人群的興趣表明，我們擁有重要的適應症和巨大的發展機會。

I think, as Marion had mentioned maybe in her prepared remarks, but if not, just to reemphasize, a large fraction of the allergists have had a great experience with DUPI in atopic dermatitis. And they make up a large fraction of the prescribers, not necessarily because they're treating patients with co-morbid conditions, although they can and that's in the label and they very well might, but the fact that they've had experience in another highly allergic disease has been so positive, I think that, that's having a nice halo effect for us, particularly amongst the allergists.

我想，正如 Marion 可能在她準備好的演講稿中提到的那樣，但如果她沒有提到，我只是想再次強調，很大一部分過敏症專家在使用 DUPI 治療異位性皮膚炎方面取得了很好的效果。他們佔處方醫生的很大一部分，這不一定是因為他們在治療患有合併症的患者（儘管他們可以這樣做，而且藥品標籤上也寫著，他們很可能會這樣做），而是因為他們在治療其他高度過敏性疾病方面的經驗非常積極，我認為這對我們來說產生了很好的光環效應，尤其是在過敏科醫生中。

Well, and just like EYLEA has an opportunity to be really paradigm shifting in terms of having the opportunity to really change the practice of how you treat high-risk diabetic retinopathy patients, I think DUPIXENT, in asthma, in particular, but in all of its settings, has a real opportunity to paradigm shifting because I think there's increasing appreciation that all of these so-called allergic or atopic diseases are really systemic conditions, where the body's immune system has gone awry and gone in the wrong direction. And the data is starting to build up, that DUPIXENT is really addressing this systemic perturbation of the immune system. And as we accumulate more and more data, more and more clinical studies and more and more indications, this may become increasingly clear and increase the opportunity. This is really paradigm shifting where you can really change the course of an immune system and how it's gone wrong, by correcting and correcting it in all of its manifestations, not just in 1 tissue and 1 organ, which is how historically the medical community treats diseases. So I think in the long term DUPIXENT really has an opportunity to be very paradigm shifting in the space as well.

就像 EYLEA 有機會真正改變高風險糖尿病視網膜病變患者的治療方式一樣，我認為 DUPIXENT，尤其是在哮喘治療方面，以及在所有應用場景中，都有機會真正改變治療方式，因為我認為人們越來越認識到，所有這些所謂的過敏性或特應性疾病實際上都是全身性疾病，是人體免疫系統失調並朝著錯誤的方向發展所致錯誤的方向發展所致錯誤的方向。越來越多的數據表明，DUPIXENT 確實能夠解決免疫系統的這種系統性失調問題。隨著我們累積越來越多的數據、越來越多的臨床研究和越來越多的適應症，這可能會變得越來越清楚，機會也會越來越大。這確實是一種範式轉變，它能夠真正改變免疫系統的進程及其出錯的方式，透過糾正和糾正其所有表現形式，而不僅僅是糾正一個組織和一個器官，而這正是醫學界歷來治療疾病的方式。所以我認為從長遠來看，DUPIXENT 確實有機會在這個領域帶來典範轉移。

Our next question comes from Adnan Butt from Guggenheim Securities.

我們的下一個問題來自古根漢證券的阿德南·巴特。

Maybe one detail. At this stage, are you able to break out that DUPIXENT asthma and atopic derm sales? And then the NBRx number, Marion, that you gave out, is that only for atopic dermatitis? Or is that a combined asthma, a-derm number?

或許是一個細節。現階段，您能否公佈DUPIXENT治療氣喘和異位性皮膚炎的銷售數據？瑪莉昂，你給我的 NBRx 號碼，是不是只適用於異位性皮膚炎？還是那是混合型氣喘，皮膚科醫生編號？

So the numbers that I gave you in NBRx access, those were combined numbers and, of course, the timing of the asthma launch for, obviously, covering the last couple of months of the year. I don't have specifics for you at this time of NBRx access broken out by indication. But as we move further into the launch window and have additional experience, we will probably be able to give some additional insights on what the splits are starting to look like.

所以我之前在 NBRx 訪問量方面給出的數字，是綜合數字，當然，氣喘產品上市的時間也考慮到了，顯然涵蓋了今年的最後幾個月。目前我還沒有按適應症細分的 NBRx 獲取途徑的具體資訊提供給您。但隨著發布窗口的進一步推進和經驗的積累，我們或許能夠對目前的市場區隔情況給予一些更深入的見解。

And our last question comes from Robyn Karnauskas from Citi.

最後一個問題來自花旗銀行的 Robyn Karnauskas。

So let me just think big picture on the DUPIXENT because people are pretty comfortable there. Can you -- and I get a lot of questions actually on food allergy because it's becoming a bigger deal globally and in the United States. What are these trials going to look like? And how do you -- how does this market tend to evolve? Because this could be something that could have maybe a quicker uptake versus, say, asthma. If you could just give us some sense of that market? Because could be the next place that you go after EoE.

所以，讓我從大局出發來談談DUPIXENT，因為人們對它相當滿意。你能回答一下嗎？ ——實際上，我經常被問到關於食物過敏的問題，因為食物過敏在全球範圍內，尤其是在美國，正變得越來越普遍。這些審判會是什麼樣的？那麼，這個市場的發展趨勢如何呢？因為與氣喘之類的疾病相比，這種疾病的接受速度可能會更快。您能否為我們介紹一下那個市場的情況？因為這可能是你玩完《新世紀福音戰士劇場版：Air/真心為你》之後要去的下一個地方。

Well, I don't know about the market opportunity. For us, it always starts with the science. And I think that if you look at the science and it's relating to what I was just talking about before and how all of these allergic conditions seem to reflect the systemic perturbation of the immune system. And interleukin-4 and interleukin-13 seem to be the central drivers of the immune deviations that's leading to this incredible uptake in allergic diseases in general and food allergies in particular. And based on our pre-clinical studies and actually a lot of other science as well, these 2 interleukins could be the central drivers in the whole process. And we believe that there is the possibility that we could be making a fundamental difference in the many patients who are suffering from food allergies. And we, of course, are in the midst of an important study with our collaborators at Aimmune to explore this. We think that the data from our grass allergy study will also be very relevant because desensitization approaches, whether they're from food allergies or from aeroallergens, in some ways, depend on the same sort of mechanisms. And we believe DUPIXENT is right centrally key in those. And we'll see what the data shows because we have these ongoing studies. And depending on the data and if it seems to hold true to the science, it could be important opportunity for so many patients who are suffering from these problems.

我不太了解市場機會。對我們來說，一切都始於科學。我認為，如果你研究科學，你會發現它與我之前所說的有關，所有這些過敏性疾病似乎都反映了免疫系統的系統性失調。白細胞介素-4 和白細胞介素-13 似乎是導致免疫偏差的主要驅動因素，從而引發過敏性疾病（尤其是食物過敏）的驚人增長。根據我們的臨床前研究以及許多其他科學研究，這兩種白細胞介素可能是整個過程的核心驅動因素。我們相信，我們有可能為眾多遭受食物過敏困擾的患者帶來根本性的改變。當然，我們目前正在與 Aimmune 的合作者進行一項重要的研究，以探索這個問題。我們認為，我們關於草過敏的研究數據也將具有非常重要的意義，因為脫敏方法，無論是食物過敏還是空氣過敏，在某種程度上都依賴同一種機制。我們認為DUPIXENT在這些方面起著至關重要的作用。我們將拭目以待，看看數據會如何顯示，因為我們正在進行這些研究。根據數據，如果結果符合科學原理，那麼對於許多遭受這些問題困擾的患者來說，這可能是個重要的機會。

So obviously, from our point of view from the market opportunity, we always like to focus on the most severe patients, which is why George mentioned when you go after perhaps peanut allergy first, or maybe later, you go after people who are children who have poly-food allergies, having difficulty driving. We certainly are all aware of anecdotes of people on DUPIXENT who tell us they were allergic to this, and they've been taking it for their atopic dermatitis, and now they're not. Obviously, that could be wishful thinking, but it's the sort of thing that we want to study. But I do agree, you are correct. In the severe poly-allergic, poly-food allergic individual, the uptake there could be quite strong. So that's going to become an increasing focus as we get through these initial trials that George referred to, grass and peanut, but plenty more to come.

所以很明顯，從我們的市場機會角度來看，我們總是喜歡專注於最嚴重的患者，這就是為什麼喬治提到，當你首先瞄準花生過敏患者，或者稍後瞄準患有多種食物過敏、難以駕駛的兒童患者時。我們當然都知道一些服用 DUPIXENT 的人告訴我們，他們對這種藥物過敏，他們之前服用 DUPIXENT 是為了治療異位性皮膚炎，但現在他們不再服用了。顯然，這可能是一廂情願的想法，但這正是我們想要研究的議題。但我同意，你是對的。對於患有嚴重多重過敏、多種食物過敏的人來說，這種藥物的吸收可能相當強。因此，隨著我們完成喬治提到的這些初步試驗（草和花生），這將逐漸成為我們越來越關注的重點，但未來還有更多試驗要做。

Great. Operator, this concludes today's call. Thank you, everyone, for joining. Again, Bob Landry, Jay Markowitz and the IR team is here to answer any further questions. Thank you.

偉大的。接線員，今天的通話到此結束。謝謝大家的參與。鮑勃·蘭德里、傑伊·馬科維茨和IR團隊再次在此回答任何其他問題。謝謝。

Thank you. Ladies and gentlemen, this concludes today's conference. Thank you for participating, and you may now disconnect.

謝謝。女士們、先生們，今天的會議到此結束。感謝您的參與，您現在可以斷開連接了。