雷傑納榮製藥 (REGN) 2021 Q4 法說會逐字稿

Welcome to the Regeneron Pharmaceuticals Fourth Quarter 2021 Earnings Conference Call. My name is Michelle, and I'll be your operator for today's call. (Operator Instructions) Please note that this conference is being recorded.

歡迎參加再生元製藥公司2021財年第四季財報電話會議。我是Michelle，將擔任本次電話會議的接線生。 （接線生說明）請注意，本次會議正在錄音。

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

現在我將把電話交給投資者關係總監馬克·哈德森。您可以開始了。

Thank you, Michelle. Good morning, good afternoon, and good evening to everyone listening around the globe. Thank you for your interest in Regeneron, and welcome to the fourth quarter 2021 conference call. An archive of this webcast will be available on our website.

謝謝米歇爾。各位全球聽眾，早安、下午好、晚上好。感謝您對再生元公司的關注，歡迎參加2021年第四季電話會議。本次網路直播的存檔將在我們的網站上提供。

Joining me on the call today are Dr. Len Schleifer, Founder, President and Chief Executive Officer; Dr. George Yancopoulos, Co-Founder, President and Chief Scientific Officer; Marion McCourt, Executive Vice President and Head of Commercial; and Bob Landry, Executive Vice President and Chief Financial Officer. After our prepared remarks, we will open up the call for Q&A.

今天與我一同參加電話會議的有：創始人、總裁兼首席執行官倫·施萊弗博士；聯合創始人、總裁兼首席科學官喬治·揚科波洛斯博士；執行副總裁兼商務主管瑪麗昂·麥考特；以及執行副總裁兼首席財務官鮑勃·蘭德里。在我們分別致詞後，我們將進入問答環節。

I'd also like to remind you that remarks today may on today's call 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 milestone, collaborations, finances, regulatory matters, payer coverage and reimbursement issues, intellectual property, pending litigation and other proceedings and competition.

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

Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-K for the period ended December 31, 2021, which we are planning to file with the SEC early next week. Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

每項前瞻性聲明均受風險和不確定性因素的影響，這些因素可能導致實際結果和事件與聲明中預測的結果和事件有重大差異。有關這些風險和其他重大風險的更完整描述，請參閱Regeneron向美國證券交易委員會提交的文件，包括截至2021年12月31日止期間的10-K表格，我們計劃於下週初向美國證券交易委員會提交該表格。 Regeneron不承擔任何更新前瞻性聲明的義務，無論是因為新資訊、未來事件或其他原因。

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

此外，請注意，今天的電話會議將討論GAAP和非GAAP財務指標。有關我們使用非GAAP財務指標以及這些指標與GAAP的調節表的信息，請參閱我們網站上發布的財務業績新聞稿。

Once our call concludes, Bob Landry and the IR team will be available to answer further questions. With that, let me turn the call over to our President and Chief Executive Officer, Dr. Len Schleifer.

通話結束後，鮑伯·蘭德里和投資者關係團隊將回答其他問題。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, Mark, and thanks to everyone joining today's call.

謝謝馬克，也謝謝今天所有參加電話會議的朋友。

The fourth quarter of 2021 capped off a terrific year for Regeneron. Our performance was driven by strong execution across the organization, despite the ongoing challenges posed by COVID-19. We're all proud of the incredible work and dedication of our employees who continuously deliver on our mission to bring important medicines and novel medical breakthroughs to patients in need.

2021年第四季為Regeneron公司輝煌的一年畫下了圓滿的句點。儘管面臨新冠疫情帶來的持續挑戰，但公司上下高效執行，依然取得了優異的業績。我們為所有員工的卓越工作和奉獻精神感到無比自豪，他們始終致力於實現我們的使命：為有需要的患者帶來重要的藥物和創新的醫學突破。

Throughout 2021, we delivered strong top and bottom line growth. Revenues, excluding our COVID antibody cocktail, grew 19%, a testament of our diversified and strengthening core business. Our innovative and world-class pipeline advanced across a wide variety of diseases.

2021年全年，我們的營收和利潤均實現了強勁成長。剔除新冠抗體雞尾酒療法後，營收成長了19%，這充分證明了我們多元化且不斷增強的核心業務實力。我們創新且世界一流的研發管線在多種疾病領域都取得了進展。

We also unveiled initial clinical data and pipeline advancements from our Regeneron Genetics medicines portfolio, which has the potential to unlock significant long-term value.

我們也發表了 Regeneron Genetics 藥物組合的初步臨床數據和研發管線進展，這些藥物組合有可能釋放巨大的長期價值。

Additionally, we returned substantial cash to shareholders in the form of share buybacks. In '21, we spent approximately $1.7 billion repurchasing over 3 million shares.

此外，我們也以股票回購的形式向股東返還了大量現金。 2021年，我們斥資約17億美元回購了超過300萬股股票。

For EYLEA, 2021 global sales grew 19% to $9.4 billion. Even after 10 years on the market and millions of injections later, we continue to view EYLEA as an enduring product, with significant future opportunity, despite new market entries.

2021年，EYLEA全球銷售額成長19%，達94億美元。即使上市10年，注射量達數百萬次，我們仍然認為EYLEA是一款經久不衰的產品，儘管有新的市場產品進入市場，但它仍具有巨大的未來發展潛力。

In the second half of the year, we look forward to the results from our Phase III aflibercept 8-milligram high-dose program. If those data continue to support that aflibercept 8 milligrams provides extended dosing duration without compromising on safety and efficacy, aflibercept 8 milligrams has the potential to complement and enhance our retinal franchise.

今年下半年，我們期待阿柏西普8毫克高劑量III期臨床試驗的結果。如果這些數據繼續支持阿柏西普8毫克能夠在不影響安全性和有效性的前提下延長給藥持續時間，那麼阿柏西普8毫克有望補充和增強我們的視網膜產品線。

With Dupixent, we are delivering on a goal of transforming the treatment of type 2 inflammatory diseases. 2021 global sales of Dupixent were $6.2 billion, representing 53% growth for the year. Looking ahead, Dupixent's outlook is bright. There are significant opportunities to increase market penetration rates in approved indications, and we are in the midst of a wave of new data submissions and launches in potential new indications, further fueling Dupixent's growth.

憑藉Dupixent，我們正在實現革新2型發炎性疾病治療的目標。 2021年Dupixent全球銷售額達62億美元，年增53%。展望未來，Dupixent前景光明。在已核准適應症領域，市場滲透率仍有顯著提升空間；同時，我們正處於新適應症資料提交和上市的高峰期，這將進一步推動Dupixent的成長。

In oncology, Libtayo continues to thrive in the approved non-melanoma skin cancers. We look forward to potential Libtayo plus chemotherapy approval later this year in the broader population of non-small cell lung cancer patients.

在腫瘤學領域，Libtayo 在已核准的非黑色素瘤皮膚癌治療中持續取得良好療效。我們期待 Libtayo 聯合化療方案今年稍後預計獲批，用於治療更廣泛的非小細胞肺癌患者群體。

Our oncology footprint continues to expand. We have advanced many candidates and combinations into the clinic with a range of antibodies, bispecifics and co-stimulatory bispecifics across many cancer settings. This year, we look forward to sharing what we hope will be groundbreaking data in difficult-to-treat solid tumors, such as prostate cancers and ovarian cancers, both of which are conditions with historically low response rates to immunotherapy.

我們在腫瘤領域的商業版圖持續擴張。我們已將多種候選藥物和聯合療法推進至臨床試驗階段，涵蓋多種抗體、雙特異性抗體和共刺激雙特異性抗體，並應用於多種癌症治療。今年，我們期待分享在難治性實體腫瘤（例如前列腺癌和卵巢癌）治療方面有望取得突破性進展的數據。這兩種癌症對免疫療法的反應率歷來都較低。

We also remain encouraged in the progress of our maturing CD3 bispecifics. We are confident in the overall safety and efficacy profile for odronextamab, our CD20xCD3 bispecific.

我們對正在研發中的CD3雙特異性抗體的進展感到鼓舞。我們對CD20xCD3雙特異性抗體odronextamab的整體安全性和有效性充滿信心。

We are forging ahead with REGN5458, our BCMAxCD3 bispecific, which we believe will play an active role in the treatment of multiple myeloma given its competitive profile.

我們正在全力推進 REGN5458 的研發，這是一款 BCMAxCD3 雙特異性抗體，我們相信，鑑於其優異的療效，它將在多發性骨髓瘤的治療中發揮積極作用。

Last but not least, we are immensely proud of our rapid response efforts against COVID-19. In 2021, REGEN-COV, our antibody cocktail, was administered to millions of people globally, making a major impact during the darkest days of the pandemic. Based on preclinical data, we recently announced that REGEN-COV is highly unlikely to be active against the Omicron variant. Appropriately, the FDA amended the emergency use authorization for REGEN-COV, limiting its use in the U.S. in light of the Omicron variant being dominant.

最後，我們為自身在應對新冠疫情方面做出的快速反應感到無比自豪。 2021年，我們的抗體雞尾酒療法REGEN-COV在全球數百萬人身上投入使用，在疫情最嚴峻的時期發揮了重要作用。基於臨床前數據，我們近期宣布REGEN-COV極不可能對Omicron變異株有效。鑑於Omicron變異株先前佔據主導地位，美國食品藥物管理局（FDA）相應地修訂了REGEN-COV的緊急使用授權，限制其在美國的使用。

Regeneron remains committed to helping fight the COVID-19 pandemic. We are progressing next-generation antibodies that are active against Omicron, Delta and other variants of concern. We are scaling up manufacturing efforts and completing the necessary requirements to begin clinical trials for next-generation candidate in the coming months.

再生元始終致力於對抗新冠肺炎疫情。我們正在推進針對奧密克戎、德爾塔及其他相關變異株的下一代抗體研發。我們正在擴大生產規模，並完成必要的準備工作，以便在未來幾個月內啟動下一代候選藥物的臨床試驗。

Concurrently, we are working closely and collaboratively with the FDA and other global regulatory authorities to establish and define clinical pathways to bring additional safe and effective monoclonal antibody treatment options to patients as quickly as possible. As one of the leaders in the fight against COVID-19, our VelociSuite platform of technologies makes us uniquely positioned to promptly develop and deliver potentially life-saving medicines.

同時，我們正與美國食品藥物管理局 (FDA) 及其他全球監管機構密切合作，制定和完善臨床路徑，以便盡快為患者提供更多安全有效的單株抗體治療方案。作為對抗 COVID-19 領域的領導者之一，我們的 VelociSuite 技術平台使我們能夠迅速開發和交付可能挽救生命的藥物，從而擁有獨特的優勢。

As the COVID-19 story transforms from pandemic to endemic, we believe there will remain a significant opportunity to use our next-generation monoclonals as a prevention for those immunocompromised individuals who do not respond adequately to COVID-19 vaccines. In addition, monoclonal antibody therapy is likely to play an ongoing role in treatment for infected individuals.

隨著新冠肺炎疫情從全球大流行轉變為地方性流行病，我們相信，對於那些對新冠疫苗反應不足的免疫功能低下人群，我們仍將擁有利用新一代單株抗體進行預防的重要機會。此外，單株抗體療法也可能在感染者的治療中繼續發揮作用。

In conclusion, 2021 was another high-performance year for Regeneron. With strong commercial results from our in-line marketed products, 30-plus pipeline candidates progressing through clinical trials, our discovery efforts firing on all cylinders, a growing portfolio of highly productive external collaborations and our strong financial position with over $12 billion in cash and marketable securities, Regeneron is extremely well positioned for the future.

總之，2021年對Regeneron而言又是業績斐然的一年。憑藉已上市產品的強勁商業表現、30多個在研藥物正在進行臨床試驗、研發工作全面展開、日益增多的高效外部合作項目，以及超過120億美元的現金和有價證券等雄厚的財務實力，Regeneron已為未來做好了充分準備。

Now I will turn the call over to George.

現在我將把電話交給喬治。

Thanks, Len. I'll start by briefly addressing our novel monoclonal antibodies for COVID-19. As Len mentioned, we are rapidly developing next-generation antibodies that retain potency against Omicron and other variants of concern.

謝謝，Len。我先簡單介紹一下我們針對新冠病毒的新型單株抗體。正如Len所提到的，我們正在快速開發新一代抗體，這些抗體對奧密克戎病毒和其他令人擔憂的變種病毒仍然有效。

Early in 2019, we anticipated that the virus would mutate and, thus, began generating large pools of virus-neutralizing antibody candidates from both human survivors and our VelocImmune mice. We have continually evaluated and refreshed this pool and now have next-generation candidates that, based on preclinical studies, effectively neutralize Omicron and other variants of concern. We're on track to initiate clinical trials with the first of these in the coming months.

2019年初，我們預料到病毒會發生變異，因此開始從人類康復者和我們的VelocImmune小鼠中篩選出大量的病毒中和抗體候選物。我們持續評估並更新這些候選物，目前已篩選出新一代候選抗體。基於臨床前研究，這些抗體能夠有效中和Omicron病毒和其他令人擔憂的變異株。我們正按計畫推進，預計在未來幾個月內啟動首個候選抗體的臨床試驗。

In addition, we are in discussions with the FDA regarding how to streamline the development program for monoclonal antibodies, considering the unwavering unmet need and demand for these medicines, especially with potential future virus variants in mind. As Len already highlighted, since we believe that monoclonal antibodies will continue to play an especially important role in the treatment of future protection of the several million immunocompromised people in the United States alone, we are committed to undertaking a development pathway that will make this possible in the near future.

此外，鑑於對單株抗體藥物的巨大未滿足需求，尤其是在考慮到未來可能出現的病毒變種的情況下，我們正在與FDA探討如何簡化單株抗體的研發流程。正如Len先前強調的，我們相信單株抗體將在治療和保護僅在美國就有數百萬免疫功能低下人群方面繼續發揮至關重要的作用，因此我們致力於採取一種能夠在不久的將來實現這一目標的研發路徑。

Moving on to ophthalmology. At the upcoming Angiogenesis meeting, we will present the final Phase II data from the aflibercept 8-milligram CANDELA study in patients with wet AMD. In this study, aflibercept 8 milligram, given at the same protocol-specified dosing schedule, as currently approved EYLEA 2-milligram met its primary safety endpoint, with measures of drawing numerically favoring the 8-milligram dose over the 2-milligram dose.

接下來談談眼科。在即將召開的血管新生會議上，我們將發表阿柏西普8毫克治療濕性老年黃斑部病變（AMD）患者的CANDELA II期研究的最終數據。在該研究中，按照與目前已批准的EYLEA 2毫克相同的方案規定的給藥方案，阿柏西普8毫克達到了其主要安全性終點，各項指標均顯示8毫克劑量組優於2毫克劑量組。

These 2 -- these Phase II results give us more confidence that the upcoming Phase III readouts has a potential to show that the higher 8-milligram aflibercept dose can at least match the efficacy and safety of EYLEA, but with more convenient dosing.

這兩個 II 期結果讓我們更有信心，即將公佈的 III 期結果有可能表明，更高的 8 毫克阿柏西普劑量至少可以與 EYLEA 的療效和安全性相媲美，而且給藥更方便。

Moving on to Dupixent. Building on the outstanding clinical success Dupixent has shown so far across a wide spectrum of allergic or type 2 inflammatory diseases, the second Phase III study in prurigo nodularis recently met primary and key secondary endpoints, making Dupixent the first and only systemic medicine to demonstrate such success in this indication.

接下來是Dupixent。 Dupixent迄今為止在多種過敏性疾病或2型發炎性疾病中均取得了卓越的臨床成功，而最近在結節性癢疹中進行的第二項III期研究也達到了主要終點和關鍵次要終點，這使得Dupixent成為第一個也是唯一一個在該適應症中取得如此成功的全身性藥物。

These data confirm the results from the first Phase III trial, where 60% of Dupixent patients met the primary endpoint of its reduction compared to 18% of placebo patients at 24 weeks.

這些數據證實了第一項 III 期試驗的結果，在 24 週時，Dupixent 組有 60% 的患者達到了主要終點（即降低劑量），而安慰劑組只有 18% 的患者達到了該終點。

Nearly 3x many Dupixent patients experienced reduced skin lesions compared to placebo as well. Prurigo nodularis marks the sixth disease for which Dupixent has demonstrated profound benefit for patients, providing convincing evidence that the IL-4 and IL-13 pathways inhibited by Dupixent are the key drivers of the type 2 inflammation underlying all of these diseases.

與安慰劑組相比，接受Dupixent治療的患者中，皮膚病變減少的比例幾乎是前者的三倍。結節性癢疹是Dupixent已證實能顯著改善患者的第六種疾病，這有力地證明了Dupixent抑制的IL-4和IL-13通路是所有這些疾病中2型發炎的關鍵驅動因素。

We have to appreciate how remarkable the Dupixent story is in terms of the important benefit it provides for the many patients across this diverse set of clinical conditions, together with its well-established safety profile, and highlights how Dupixent is delivering on its promise of providing a pipeline in a product.

我們必須認識到 Dupixent 的發展歷程是多麼卓越，它為眾多患有各種臨床疾病的患者帶來了重要的益處，同時其安全性也得到了充分證實，這凸顯了 Dupixent 如何兌現其在產品研發方面提供產品線的承諾。

At the upcoming AAAAI meeting, in addition to the other important Dupixent updates, we will present pivotal results for the recent top line studies in eosinophilic esophagitis, or EOE, and for the first chronic spontaneous urticaria, or CSU study. EOE is a complex disease, and we are excited to share these data with the scientific community and patients. Our first regulatory submission for EOE in adolescents and adults is underway, with regulatory submissions for prurigo nodularis also starting in the first half of this year.

在即將召開的美國過敏、氣喘和免疫學會 (AAAAI) 年會上，除了其他重要的 Dupixent 最新進展外，我們還將公佈近期嗜酸性食道炎 (EOE) 一線研究的關鍵結果，以及首個慢性自發性蕁麻疹 (CSU) 研究的結果。 EOE 是一種複雜的疾病，我們很高興能與科學界和患者分享這些數據。我們針對青少年和成人 EOE 的首個監管申請正在進行中，針對結節性癢疹的監管申請也將於今年上半年啟動。

Anticipated flow of Dupixent-related clinical data update continues. We are planning on reporting results in an additional Phase III study in CSU this time in omalizumab experienced patients and also for the chronic cold-induced urticaria indication in the second half of this year.

Dupixent相關臨床數據更新的預期進展仍在繼續。我們計劃在今年下半年公佈一項針對慢性自發性蕁麻疹（CSU）的III期研究結果，該研究納入了既往接受過奧馬珠單抗治療的患者，並同時報告了Dupixent治療慢性寒冷誘發蕁麻疹的適應症。

These represents more difficult-to-treat patients or condition and present a higher bar for Dupixent. We're looking forward to results of these pivotal studies.

這些病例代表了更難治療的患者或病情，也對Dupixent提出了更高的要求。我們期待這些關鍵性研究的結果。

Moving on to oncology and first Libtayo. Progress in our oncology portfolio includes pivotal readouts and regulatory filings for Libtayo presented an anticipated data readouts for our bispecifics as well as multiple upcoming milestones with novel diversified pipeline entrants. As Len mentioned, the Libtayo chemotherapy combination for patients with non-small cell lung cancer is under review at the FDA with a PDUFA date of September 19, 2022, which could address a larger portion of the patients with lung cancer.

接下來談談腫瘤領域，首先是Libtayo。我們在腫瘤產品組合方面取得了進展，Libtayo的關鍵性數據已公佈，監管文件也已提交。此外，我們也公佈了雙特異性抗體的預期數據，以及多個即將取得里程碑式進展的新型多元化產品線。正如Len所提到的，Libtayo用於治療非小細胞肺癌的化療聯合方案正在接受FDA的審查，預計PDUFA批准日期為2022年9月19日，這將使更多肺癌患者受益。

In hematology, at the American Society of Hematology Annual Meeting, we presented encouraging data for REGN5458, our BCMAxCD3 bispecific, investigated for relapsed or refractory multiple myeloma, with safety data that has shown no grade 3 or higher cytokine release syndrome to date and strong efficacy data.

在血液學領域，我們在美國血液學會年會上展示了 REGN5458 的令人鼓舞的數據，REGN5458 是一種 BCMAxCD3 雙特異性抗體，用於治療復發或難治性多發性骨髓瘤，其安全性數據顯示迄今為止尚未出現 3 級或更高級別的細胞因子釋放綜合徵，並且療效數據非常顯著。

We believe our investigational agent is promising and has the potential to be competitive in this indication. We are planning on investigating this product for earlier lines of myeloma therapy, in combination with standard of care, and are excited about the combination with an appropriate co-stimulatory bispecific, which could further enhance responses.

我們相信，我們的在研藥物前景廣闊，並有望在這個適應症領域展現競爭力。我們計劃研究該產品與標準療法聯合用於早期多發性骨髓瘤治療的療效，並對與合適的共刺激雙特異性抗體聯合使用充滿期待，因為這可能進一步增強療效。

Odronextamab, our CD20xCD3 bispecific, has the potential for a best-in-class efficacy profile in both follicular lymphoma and diffuse large B-cell lymphoma, and our updated step-up dosing protocol may mitigate safety concerns and decrease the need for hospitalizations to manage cytokine release syndrome.

我們的 CD20xCD3 雙特異性抗體 Odronextamab 在濾泡性淋巴瘤和瀰漫性大 B 細胞淋巴瘤方面具有同類最佳的療效，我們更新的遞增劑量方案可能會減輕安全問題，並減少因治療細胞激素釋放綜合徵而需要住院治療的情況。

In terms of progress of our bispecifics for solid tumors, as previously disclosed, we are observing early signs of activity for our MUC16xCD3 bispecific monotherapy developed for late-stage ovarian cancer, and we are excited to be sharing these early data later this year.

就我們針對實體瘤的雙特異性抗體的進展而言，正如先前披露的那樣，我們觀察到針對晚期卵巢癌開發的 MUC16xCD3 雙特異性單藥療法已出現早期活性跡象，我們很高興能在今年稍後分享這些早期數據。

In addition to monotherapy, the MUC16xCD3 bispecific is being investigated in combination with Libtayo and in a first of its kind in a combination trial with a MUC16xCD28 bispecific. These combinations are in early stages that are advancing through dose escalations.

除了單藥治療外，MUC16xCD3雙特異性抗體正在與Libtayo聯合用藥進行研究，並且首次開展了與MUC16xCD28雙特異性抗體聯合用藥的臨床試驗。這些合併用藥方案尚處於早期階段，目前正在進行劑量遞增試驗。

Later this year, we are hoping to share initial results for a unique biparatopic MET X MET antibody studied in advanced non-small cell cancer patients with MET protein alterations. Early signs of clinical activity we have observed so far with the naked MET X MET bispecific antibody, especially in patients with MET overexpression, bode well for our follow-on agents, the MET X MET bispecific antibody drug conjugate, which is now enrolling patients in a Phase I study.

今年晚些時候，我們希望分享一項針對MET蛋白改變的晚期非小細胞肺癌患者的獨特雙位點MET X MET抗體的初步研究結果。目前，我們觀察到裸露的MET X MET雙特異性抗體，尤其是在MET過度表現患者中，已展現出早期臨床活性，這預示著我們的後續藥物——MET X MET雙特異性抗體藥物偶聯物——也將取得良好療效。該藥物偶聯物目前正在進行I期臨床試驗，招募病患。

We are also excited about our early-stage EGFRxCD28 co-stimulatory bispecific program for lung and other cancers.

我們也對我們針對肺癌和其他癌症的早期 EGFRxCD28 共刺激雙特異性抗體計畫感到興奮。

For prostate cancer, we are expecting initial readouts from our first co-stimulatory bispecific PSMAxCD28 later this year as well. PSMAxCD28 is progressing through dose escalation in combination with Libtayo.

對於前列腺癌，我們預計今年稍後也將獲得首個共刺激雙特異性抗體PSMAxCD28的初步結果。 PSMAxCD28目前正與Libtayo合併進行劑量遞增試驗。

We are excited about the potential of our broad oncology portfolio, which includes multiple Phase I, II and III assets, as many are beginning to believe the future is going to involve the right combination of targeted immunotherapy agents.

我們對自身廣泛的腫瘤產品組合的潛力感到興奮，其中包括多個 I 期、II 期和 III 期資產，因為許多人開始相信，未來將涉及靶向免疫療法藥物的正確組合。

Concluding with our Regeneron Genetic medicines efforts, we and our collaborators have made significant strides in expanding the capabilities and scale of our groundbreaking work in genetics medicines. In terms of our siRNA collaboration with Alnylam, ALN-HSD is progressing through healthy volunteers, and initial data in NASH patients are anticipated by the middle of this year.

最後，我們回顧一下Regeneron基因藥物項目，我們和我們的合作夥伴在擴展基因藥物領域突破性研究的能力和規模方面取得了顯著進展。在與Alnylam的siRNA合作方面，ALN-HSD正在健康志願者中進行試驗，預計今年年中獲得NASH患者的初步數據。

With the C5 siRNA and the antibody combination, another first of its kind, healthy volunteer data were presented at ASH, demonstrating PK and PD results supportive of the monthly subcutaneous dosing regimen selected for pivotal studies.

在 ASH 上，C5 siRNA 和抗體組合又首次展示了健康志願者的數據，證明了 PK 和 PD 結果支持為關鍵研究選擇的每月皮下給藥方案。

Phase III studies of the combination for paroxysmal nocturnal hemoglobinuria, or PNH, were also initiated. Recall, in PNH, we are planning to test our combination in both naive and switch patients tested against standard of care therapies, including ravulizumab and eculizumab.

針對陣發性睡眠性血紅素尿症（PNH）的合併療法III期研究也已啟動。回顧一下，在PNH治療中，我們計劃在初治患者和轉換治療患者中測試該聯合療法，並將其與包括ravulizumab和eculizumab在內的標準療法進行比較。

Also Alnylam has recently announced submission of the CTA application for ALN-APP, the industry's first-ever investigational RNAi therapeutic for CNS diseases. This agent will be evaluated in both the relatively rare disease driven by amyloid precursor protein, known as cerebral amyloid angiopathy, or CAA, as well as in early-onset Alzheimer's disease.

此外，Alnylam公司近期宣布已提交ALN-APP的臨床試驗申請（CTA），ALN-APP是業界首個用於治療中樞神經系統疾病的在研RNAi療法。該藥物將針對兩種疾病進行評估：一種是相對罕見的由澱粉樣前體蛋白驅動的疾病，即腦澱粉樣血管病變（CAA）；另一種是早發性阿茲海默症。

Finally, later this quarter, we and Intellia will provide our -- an update on our joint TTR CRISPR-based knockout program for transthyretin amyloidosis. This will include additional ascending dose interim clinical data from the polyneuropathy arm of the ongoing Intellia 2001 Phase I study.

最後，在本季晚些時候，我們和Intellia將發布我們共同進行的基於CRISPR技術的TTR基因敲除計畫（用於治療轉甲狀腺素蛋白澱粉樣變性）的最新進展。這將包括正在進行的Intellia 2001 I期臨床試驗中多發性神經病變組的更多遞增劑量中期臨床數據。

We have also expanded the study to include patients with transthyretin amyloidosis with cardiomyopathy, which we believe will address an even broader patient population.

我們也擴大了研究範圍，納入了患有轉甲狀腺素蛋白澱粉樣變性伴隨心肌病變的患者，我們相信這將涵蓋更廣泛的患者群體。

We are very excited by our large and diverse pipeline of siRNA candidates that we are advancing with Alnylam, ranging from targeting the liver, the brain and the eye, as well as our CRISPR-based approaches in collaboration with Intellia and our viral-targeted gene delivery programs, such as with Decibel. While still early, we think these groundbreaking approaches have the potential to change the practice of medicine.

我們與Alnylam合作推進的siRNA候選藥物種類繁多、靶向肝臟、大腦和眼睛，以及我們與Intellia合作的基於CRISPR的技術，還有我們與Decibel等公司合作的病毒靶向基因遞送項目，這些都讓我們倍感振奮。雖然目前仍處於早期階段，但我們相信這些突破性的方法有望改變醫學實踐。

And with that, I will turn the call over to Marion.

接下來，我將把電話交給瑪莉安。

Thank you, George.

謝謝你，喬治。

Our fourth quarter business performance demonstrated the strength and resilience of our in-line brands and creates a foundation for commercial success as we prepare for future launches.

我們第四季的業務表現展現了我們現有品牌的實力和韌性，並為我們未來推出新產品奠定了商業成功的基礎。

Starting with EYLEA. We recently announced fourth quarter U.S. net sales of $1.55 billion and $5.79 billion in 2021. This represented 17% year-over-year U.S. growth for the full year, which is noteworthy for a brand 10 years post launch.

首先是安樂。我們最近公佈了第四季美國淨銷售額為15.5億美元，2021年全年淨銷售額為57.9億美元。這代表著全年美國市場年增17%，對於一個上市10年的品牌來說，這是一個值得關注的成績。

EYLEA reached record share across all approved indications and is the recognized leader in a category that continues to grow due to favorable demographic trends. EYLEA remains physicians' top choice for patients with indicated retinal diseases due to its demonstrated efficacy, safety, dosing flexibility and unsurpassed real-world experience, with more than 40 million administered injections worldwide.

EYLEA 在所有核准適應症中均創下市場份額新高，並憑藉其在人口結構有利趨勢下持續增長的領域中，穩居市場領先地位。 EYLEA 療效顯著、安全性高、給藥方案靈活，且擁有豐富的真實世界經驗（全球注射量超過 4000 萬次），因此始終是醫生治療適應症視網膜疾病患者的首選藥物。

We are also excited about ongoing strategic initiatives that position our retinal franchise for future growth, such as our educational efforts in place across existing indications where many patients don't receive the treatment they need.

我們也對正在進行的策略性舉措感到興奮，這些舉措將使我們的視網膜業務在未來實現成長，例如我們在現有適應症中開展的教育工作，因為許多患者沒有得到他們需要的治療。

Beyond EYLEA, we are encouraged by promising early results for high-dose aflibercept 8 milligram, which, if supported by Phase III clinical results, potentially represents next-generation treatment for a range of eye diseases.

除了 EYLEA 之外，高劑量阿柏西普 8 毫克的早期結果也令人鼓舞，如果 III 期臨床結果支持，它有可能成為治療一系列眼部疾病的下一代療法。

Turning to Libtayo, where global net sales in the fourth quarter were $121 million, in the U.S., net sales reached $81 million. In advanced cutaneous squamous cell carcinoma, which currently drives majority of performance, Libtayo is the #1 systemic treatment, and we saw steady growth as the market continued its post-COVID recovery.

Libtayo第四季全球淨銷售額達1.21億美元，其中美國淨銷售額為8,100萬美元。在目前貢獻了大部分業績的晚期皮膚鱗狀細胞癌領域，Libtayo是排名第一的全身性治療藥物，隨著市場在新冠疫情後持續復甦，我們看到了穩定成長。

In advanced basal cell carcinoma, Libtayo is also rapidly being established as standard of care in patients who have progressed or are inappropriate for hedgehog inhibitors, building on our strength in non-melanoma skin cancers.

對於晚期基底細胞癌，Libtayo 也正在迅速成為治療進展或不適合使用 hedgehog 抑制劑的患者的標準療法，這建立在我們非黑色素瘤皮膚癌方面的優勢之上。

In advanced non-small cell lung cancer, we are making progress in the launch of our monotherapy indication with a steadily growing prescriber base. There is also significant opportunity in the chemotherapy combination setting. And if proved, Libtayo would be available for a much broader range of first-line lung cancer patients than for monotherapy alone. Our experience is that medical oncologists consider combination treatment first and reserve monotherapy for a much smaller group of patients, which, in part, has limited Libtayo uptake in lung cancer to date.

在晚期非小細胞肺癌領域，我們的單藥療法適應症推廣進展順利，處方醫師群體也穩定成長。化療合併治療方面也蘊藏著巨大的潛力。如果療效得到證實，Libtayo 將比單純單藥治療覆蓋更廣泛的第一線肺癌患者。我們的經驗表明，腫瘤內科醫生通常會優先考慮聯合治療，而將單藥治療保留給一小部分患者，這在一定程度上限制了 Libtayo 在肺癌領域的應用。

Briefly turning to our cardiovascular franchise. Evkeeza, our treatment for patients with HoFH, was successfully launched in 2021 and is already the standard of care. We continue to see initiations in both switch and category naive patients. In 2021, we are focused on employing innovative efforts to identify patients not currently diagnosed with HoFH.

簡單介紹一下我們的心血管業務。 Evkeeza 是我們針對純合子家族性高膽固醇血症 (HoFH) 患者的治療方案，已於 2021 年成功上市，並已成為標準治療方案。我們持續看到新患者（包括轉換治療患者和初治患者）開始接受該藥物治療。 2021 年，我們將致力於透過創新舉措，識別目前尚未確診為 HoFH 的患者。

On to Dupixent, which grew 51% in global net sales in the fourth quarter year-over-year to $1.77 billion, in the U.S., net sales grew 46% to $1.35 billion. Dupixent is well positioned for ongoing rapid growth based on significant unmet need in existing and potential new disease areas, with anticipated expansion into even younger age groups and new geographies worldwide.

接下來是Dupixent，第四季全球淨銷售額年增51%至17.7億美元，在美國的淨銷售額成長46%至13.5億美元。 Dupixent在現有和潛在的新疾病領域存在巨大的未滿足需求，預計未來將進一步拓展至更年輕的年齡群體和全球新的地區，因此有望實現持續快速增長。

In atopic dermatitis, prescribing trends are strong across the spectrum of moderate to severe disease. Dupixent is health care specialists' first-line systemic treatment of choice due to several highly differentiating product characteristics, including its dual anti-IL-4 and IL-13 mechanism of action, compelling efficacy and rapid symptom relief, well-established safety profile, with no risk of serious infections due to immunosuppression and clinical data in children as young as 6 months.

在異位性皮膚炎領域，從中度到重度疾病，處方趨勢均十分強勁。 Dupixent 因其多項顯著的產品特性，成為醫療專家首選的第一線全身性治療藥物。這些特性包括：雙重抗 IL-4 和 IL-13 作用機制、顯著的療效和快速緩解症狀、完善的安全性（無免疫抑制引起的嚴重感染風險），以及在 6 個月大嬰兒的臨床數據。

If approved, we look forward to expanding Dupixent's skin indications to include babies and young children with atopic dermatitis as well as 2 new dermatologic indications. There are no currently approved biologic medicines for prurigo nodularis, where we estimate approximately 75,000 patients may benefit from Dupixent in the U.S. alone. We're also progressing an important opportunity to help chronic spontaneous urticaria patients.

如果獲得批准，我們期待將Dupixent的皮膚適應症擴展至包括患有異位性皮膚炎的嬰幼兒，以及另外兩種新的皮膚病適應症。目前尚無核准的生物製劑用於治療結節性癢疹，我們估計僅在美國就有約75,000名患者可能受益於Dupixent。此外，我們也積極推動一項重要的研發計劃，以幫助慢性自發性蕁麻疹患者。

Dupixent is also steadily growing in the highly competitive asthma space. We see ongoing potential to differentiate Dupixent in moderate to severe disease through its competitive profile, including a broad label that allows use in uncontrolled steroid-dependent patients, regardless of their eosinophil levels, as well as use in patients as young as 6 years of age.

在競爭激烈的氣喘治療領域，Dupixent 也穩定成長。我們看到，憑藉其具有競爭力的特性，Dupixent 在中重度氣喘治療領域持續展現出差異化優勢，其適應症範圍廣泛，包括可用於治療未控制的激素依賴型氣喘患者（無論其嗜酸性粒細胞水平如何），以及可用於治療 6 歲及以上的兒童患者。

Dupixent is also the preferred treatment of ENTs and allergists in chronic rhinosinusitis with nasal polyps, regardless of prior surgery and contributes meaningfully to our business.

Dupixent 也是耳鼻喉科醫生和過敏科醫生治療慢性鼻竇炎伴鼻息肉的首選藥物，無論之前是否接受過手術，並且對我們的業務做出了重要貢獻。

We are also progressing our launch plans for eosinophilic esophagitis, a gastrointestinal disease with substantial unmet need. We estimate at least 50,000 patients in the U.S. could benefit from Dupixent if approved. We've received positive feedback from key opinion leaders on the strength of our data and lack of suitable treatment alternatives for this serious disease.

我們也正在推動嗜酸性食道炎的上市計劃，這是一種胃腸道疾病，目前存在大量未被滿足的醫療需求。我們估計，如果Dupixent獲得批准，美國至少有5萬名患者將從中受益。我們已收到關鍵意見領袖的正面回饋，他們對我們的數據優勢以及目前針對這種嚴重疾病缺乏合適的替代療法表示讚賞。

In summary, in 2021, our commercial team delivered strong growth across the portfolio. Our momentum and new launch opportunities position us well for the future growth.

總而言之，2021年，我們的商業團隊實現了全線產品組合的強勁成長。我們目前的成長動能和新產品上市的機遇，為我們未來的發展奠定了堅實的基礎。

Now I'll turn the call over to Bob.

現在我把電話交給鮑伯。

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

謝謝，瑪莉安。我今天對再生元公司財務業績和展望的評論，在適用情況下將採用非GAAP準則。

Regeneron's fourth quarter capped off a strong year. In the quarter, we delivered top and bottom line growth driven by strong execution within our core business.

再生元第四季業績為強勁的一年畫上了圓滿的句號。本季度，由於核心業務的出色執行，我們實現了營收和利潤的雙重成長。

Fourth quarter total revenue grew 104% year-over-year to $5 billion. Excluding revenues related to the COVID-19 antibody cocktail, total fourth quarter revenue grew 17% year-over-year to $2.7 billion, demonstrating continuing strength of our core business.

第四季總營收年增104%，達50億美元。若不計入與新冠病毒抗體雞尾酒療法相關的收入，第四季總收入年增17%，達到27億美元，顯示我們核心業務持續強勁。

Fourth quarter total diluted net income per share was $23.72 on net income of $2.7 billion.

第四季稀釋後每股淨收益為 23.72 美元，淨收益為 27 億美元。

Starting with REGEN-COV. In the fourth quarter, we delivered the remaining 1.1 million doses from our September 2021 U.S. government supply agreement and recognized $2.3 billion of U.S. net sales. In accordance with our global collaboration with Roche, the amount of manufactured products supplied by each party to the global market resulted in the recognition of a true-up payment related to Roche's share of profits. As a result, in the fourth quarter, we recognized a $260 million charge in cost of goods sold and recorded no Roche collaboration revenue.

首先來看REGEN-COV疫苗。第四季度，我們交付了2021年9月與美國政府簽訂的供應協議中剩餘的110萬劑疫苗，並確認了23億美元的美國淨銷售額。根據我們與羅氏的全球合作協議，雙方向全球市場供應的疫苗數量導致我們確認了一筆與羅氏利潤份額相關的調整付款。因此，第四季度我們確認了2.6億美元的銷售成本費用，並且沒有確認任何與羅氏合作相關的收入。

As mentioned, we completed all deliveries under the September 2021 U.S. government supply contract in the fourth quarter. With the FDA's recent amendment to REGEN-COV's emergency use authorization, we do not expect to record any U.S. REGEN-COV sales in the first half of 2022.

如前所述，我們已於第四季完成了2021年9月美國政府供應合約下的所有交付。鑑於FDA近期對REGEN-COV緊急使用授權的修訂，我們預計2022年上半年不會錄得任何美國REGEN-COV銷售額。

I will now move to our collaborations, starting with Bayer. Fourth quarter 2021 ex-U.S. EYLEA net product sales as reported to us by Bayer were $934 million, growing 9% on a reported basis and 12% on a constant currency basis. Total Bayer collaboration revenue was $372 million, of which we recorded $354 million for our share of net profits from EYLEA sales outside the U.S.

接下來我將談談我們的合作，首先是與拜耳的合作。根據拜耳提供給我們的資料，2021年第四季除美國以外，EYLEA淨產品銷售額為9.34億美元，按報告匯率計算成長9%，以固定匯率計算成長12%。拜耳合作總收入為3.72億美元，其中我們計入了來自美國以外EYLEA銷售的3.54億美元淨利份額。

Total Sanofi collaboration revenue was $518 million in the fourth quarter of 2021. Despite seasonally higher fourth quarter operating expenses, our share of the profits from the commercialization of Dupixent and Kevzara was $388 million, which compares favorably to our share of profits of $230 million in the fourth quarter of last year.

2021 年第四季度，賽諾菲合作總營收為 5.18 億美元。儘管第四季度營運費用季節性較高，但我們從 Dupixent 和 Kevzara 的商業化中獲得的利潤份額為 3.88 億美元，與去年第四季我們獲得的 2.3 億美元利潤份額相比，情況有所好轉。

Moving now to fourth quarter 2021 operating expenses. R&D decreased slightly to $639 million primarily due to lower spending on REGEN-COV development as compared to the fourth quarter of 2020.

現在來看2021年第四季的營運支出。研發支出略降至6.39億美元，主要是因為與2020年第四季相比，REGEN-COV的研發支出減少。

SG&A expense increased 30% year-over-year to $495 million primarily due to cost related to growth initiatives for EYLEA and higher head count-related costs.

銷售、一般及行政費用年增 30% 至 4.95 億美元，主要原因是與安永 (EYLEA) 成長計畫相關的成本以及與人員增加相關的成本。

Cost of goods sold were $559 million primarily related to REGEN-COV manufacturing costs and, as I mentioned earlier, the recognition of the $260 million true-up payment to Roche for their share of profits related to the COVID antibody cocktail.

銷售成本為 5.59 億美元，主要與 REGEN-COV 的生產成本有關，正如我之前提到的，還確認了向羅氏支付的 2.6 億美元，作為其在 COVID 抗體雞尾酒療法中應得的利潤份額。

Finally, the fourth quarter 2021 effective tax rate was 12.7%.

最後，2021 年第四季的實際稅率為 12.7%。

Shifting now to cash flow and the balance sheet. For the year, Regeneron generated $6.5 billion in free cash flow and ended the year with cash and marketable securities less debt of $9.8 billion.

接下來我們來看現金流和資產負債表。 Regeneron公司本年度自由現金流為65億美元，年末現金及有價證券減去債務後餘額為98億美元。

In the fourth quarter 2021, we exhausted the remaining balance on our $1.5 billion share repurchase authorization. And in November, we announced a new $3 billion share repurchase authorization. Across both, we've repurchased approximately 850 million of shares in the fourth quarter of 2021. We continue to be opportunistic buyers where we see dislocation between our stock price and our intrinsic valuation.

2021年第四季度，我們用完了15億美元股票回購授權的剩餘額度。 11月，我們宣布了一項新的30億美元股票回購授權。這兩項措施加起來，我們在2021年第四季共回購了約8.5億股股票。我們將繼續抓住機會，在股價與其內在價值出現偏差時進行買入。

Now let me conclude with our initial 2022 outlook and guidance. As I mentioned earlier, we do not expect to record any U.S. REGEN-COV sales in the first half of 2022.

現在，讓我總結一下我們對2022年的初步展望和指導。正如我之前提到的，我們預計2022年上半年在美國不會有任何REGEN-COV的銷售。

For U.S. Praluent throughout 2021, we observed significant category and competitive pressures. We expect these pressures to accelerate throughout 2022.

2021年全年，美國Praluent市場面臨顯著的品類與競爭壓力。我們預計這些壓力將在2022年加劇。

And now for our 2022 expense guidance. For R&D, we forecast our 2022 R&D expense to be in the range of $2.8 billion to $3 billion. As we highlighted throughout 2021, critically important development programs are advancing in 2022, including the late-stage randomized studies versus branded comparators for the LAG3 Libtayo combination, BCMAxCD3 and C5 programs in development expenses to advance next-generation antibodies against COVID-19.

接下來是我們的2022年費用預期。研發方面，我們預計2022年的研發費用將在28億美元至30億美元之間。正如我們在2021年多次強調的那樣，一些至關重要的研發項目將在2022年取得進展，包括LAG3/Libtayo聯合療法的後期隨機對照試驗（與品牌對照藥物進行比較）、BCMAxCD3以及C5項目，這些研發項目旨在推進針對COVID-19的下一代抗體的研發。

For SG&A, we forecast our 2022 SG&A expense to be in the range of $1.65 billion to $1.77 billion. Based on our initial plan, we expect SG&A expenses to be spread evenly across the quarters in 2022.

對於銷售、管理及行政費用（SG&A），我們預測2022年的SG&A費用將在16.5億美元至17.7億美元之間。根據我們最初的計劃，我們預計2022年的SG&A費用將平均分攤到各個季度。

For COGS, we forecast 2022 product gross margin on our percentage of net product sales to be between 90% and 92%. We expect cost of collaboration manufacturing to be in the range of $750 million to $830 million driven by continued growth in our Dupixent franchise.

對於銷售成本，我們預測2022年產品毛利率（佔淨產品銷售額的百分比）將在90%至92%之​​間。我們預計，受Dupixent產品線持續成長的推動，合作生產成本將在7.5億美元至8.3億美元之間。

And finally, we anticipate our 2022 effective tax rate to be in the range of 13% to 15%. A complete summary of our full year guidance is available in our press release issued earlier this morning.

最後，我們預計2022年的實際稅率將在13%至15%之間。我們今天早些時候發布的新聞稿中提供了全年業績指引的完整摘要。

In conclusion, our core business continues to advance and strengthen. With growth continuing across our existing portfolio and investments in our R&D engine supported by our strong balance sheet, we remain well positioned for sustainable long-term growth.

總之，我們的核心業務持續發展壯大。憑藉現有業務組合的持續成長以及研發投入，再加上我們穩健的資產負債表，我們仍處於實現永續長期成長的有利地位。

Thanks, Bob. Michelle, that concludes our prepared remarks. We now like to open up the call for Q&A. (Operator Instructions) Please go ahead, Michelle.

謝謝，鮑伯。米歇爾，我們的演講到此結束。現在進入問答環節。 （操作說明）米歇爾，請開始。

(Operator Instructions) Our first question comes from Evan Seigerman with BMO.

（操作說明）我們的第一個問題來自 BMO 的 Evan Seigerman。

You touched on your solid tumor oncology franchise, specifically the MET X MET in MUC16xCD3 bispecifics that we're supposed to get this year. Can you elaborate a little as to kind of what we should be expecting with these data readouts and how that could inform potentially pivotal trials or a registration path?

您剛才提到了您的實體腫瘤治療產品線，特別是我們今年應該能獲得的MET X MET靶向MUC16xCD3雙特異性抗體。您能否詳細說明我們應該對這些數據解讀抱持什麼樣的預期，以及這些數據將如何指導潛在的關鍵性試驗或註冊流程？

Yes. These are both being evaluated in late-stage patients who have essentially failed all existing therapies. And obviously, the excitement would be if one saw evidence of convincing objective responses that were durable in these settings, then those would certainly inform how would we move forward on these.

是的。這兩種療法都在晚期患者中進行評估，這些患者基本上已經對所有現有療法都無效。顯然，如果能在這些患者身上看到令人信服且持久的客觀療效，那將非常令人振奮，因為這無疑會引導我們下一步的治療方向。

And we've already announced that we've been observing encouraging early signs of efficacy, and we will be elaborating on these and giving the details in these future presentations.

我們已經宣布，我們觀察到了一些令人鼓舞的早期療效跡象，我們將在未來的演講中詳細闡述這些跡象並提供詳細資訊。

Our next question comes from Carter Gould with Barclays.

下一個問題來自巴克萊銀行的卡特·古爾德。

Maybe I'll just take on the elephant in the room. For Len and Marion, would love to get your thoughts on -- as you think about the EYLEA franchise in the context of what looks like a very accommodating label on faricimab and their pricing, as we think about the implications for your high-dose label and commercial positioning.

或許我應該直面這個顯而易見的問題。 Len 和 Marion，我很想聽聽你們對 EYLEA 系列產品的看法——考慮到 faricimab 的標籤似乎非常寬鬆，定價也比較合理，這會對你們的高劑量標籤和商業定位產生什麼影響？

Yes. I'll let Marion get into the details. But we don't see faricimab as a transformative therapy of any kind, notwithstanding any label. It's very hard to see when you look at it dispassionately any scientific evidence for the contribution of Ang2 blockade.

是的，我會讓瑪莉安詳細解釋。但我們並不認為法瑞西單抗是一種變革性療法，無論它被貼上了什麼標籤。客觀地來看，很難找到任何科學證據顯示血管張力素II受體阻斷劑的作用。

People forget, nobody has a greater interest and would love to see Ang2 blockade being a value given that George and his colleagues were the ones who discovered and cloned Ang2, the first in the world on that. But there's really no evidence that we can see where you've separated that out.

人們往往忘記了，沒有人比喬治和他的同事更關心Ang2阻斷技術的價值，畢竟他們是世界上第一個發現並複製Ang2的人。但實際上，我們根本看不到你是如何將它分開的。

So what we're seeing here is a higher dose of faricimab relative to Lucentis and possibly on a [moral] basis relative to EYLEA. We remind everybody that there are a lot of lessons learned here. One of the biggest lessons is efficacy is super important, but well beyond that is safety. And nothing right now contract the, I don't know, almost 50 million injections that have been given worldwide with EYLEA.

所以，我們現在看到的是，法瑞西單抗的劑量比雷珠單抗（Lucentis）更高，而且從倫理角度來看，可能也比艾來恩（EYLEA）更高。我們提醒大家，這裡有很多值得學習的教訓。其中最重要的一點是，療效固然重要，但安全性遠比療效重要。目前還沒有任何藥物能與艾來恩（EYLEA）在全球近5000萬次的注射量相提並論。

So we feel pretty good. The competition is always good. Obviously, competition is going to eat into a product. We suspect that faricimab may take a lot of the -- of its share initially from Lucentis, but we'll see.

所以我們感覺還不錯。競爭總是好事。當然，競爭肯定會蠶食產品的市佔率。我們估計，法瑞西單抗最初可能會從盧森蒂斯手中搶走很多市場份額，但我們拭目以待。

Marion might want to elaborate.

瑪莉昂或許想詳細說明一下。

Yes. Thank you, Len. Certainly, to give some very early market feedback, the comment that we're getting from key opinion leaders is that they don't see first [met via] product that potentially is a game changer and that the dosing is complex. And there are remaining questions on the clinical trial design and, of course, as Len mentioned, safety.

是的，謝謝你，Len。當然，就目前市場回饋而言，我們從關鍵意見領袖那裡得到的評價是，他們認為目前還沒有出現一款能夠顛覆產業格局的首創產品，而且給藥方案也比較複雜。此外，臨床試驗設計以及安全性方面也存在一些疑問，如Len所提到的。

More importantly, I'll go back over to EYLEA, where we certainly are establishing the product as standard of care and more across indications with great flexibility of dosing, indications, experience, real-world evidence, prefilled syringe and busy times. So we look forward to strong performance going forward on EYLEA, and we're very optimistic about what could be a next-generation product with our own aflibercept 8-milligram high-dose product if the Phase III data works out.

更重要的是，我會回到EYLEA計畫上來，我們正在努力將該產品確立為標準療法，並使其在多種適應症中得到更廣泛的應用，其劑量、適應症、經驗、真實世界證據、預充式註射器以及在繁忙時段的療效都具有極大的靈活性。因此，我們期待EYLEA計畫未來能夠取得強勁的進展，並且如果III期臨床試驗數據理想，我們對我們自主研發的8毫克高劑量阿柏西普產品作為下一代產品充滿信心。

Our next question comes from Tyler Van Buren with Cowen.

下一個問題來自 Cowen 公司的 Tyler Van Buren。

So for your next-generation COVID antibody cocktail, looks like it's -- you said it's entering the clinic in the coming months. So was there a slight delay versus the prior Q1 guidance?

所以，關於你們的下一代新冠抗體雞尾酒療法，你說過它將在未來幾個月進入臨床試驗階段。那麼，與之前第一季的預期相比，是否略有延遲？

And you referred to FDA streamlining development of monoclonal antibodies. So can you give us your latest thoughts on how long it might take to get to market? I noticed Bob mentioned that there won't be sales in the first half, so just curious if we could see something in the second half.

您提到FDA正在簡化單株抗體的研發流程。能否談談您對產品上市所需時間的最新看法？我注意到Bob提到上半年不會有銷售，所以我想知道下半年是否有可能看到一些進展。

Yes. George can comment on what he thinks is necessary, but I just want to be clear. I don't think there's any delay, whether we come in just at the end of this quarter or early in the next quarter or thereabouts. It's tough to exactly estimate when we'll start. But we're scaling up, and we're rolling forward.

是的。喬治可以就他認為必要的事項發表意見，但我只想澄清一點。我認為不會有任何延誤，無論是在本季度末、下季度初還是前後幾個時間段。很難準確估計我們何時開始。但我們正在擴大規模，並穩步推進。

George can comment on some of the global and U.S. regulatory considerations and guidances that we know about thus far.

喬治可以就我們目前所了解的一些全球和美國監管方面的考慮因素和指導意見發表評論。

Yes. There's not much to add. I mean, we're continuing to discuss with regulators what the program is and what are the abilities as was done with vaccines to expedite the development programs compared to what was necessary for the first-generation agents developed using the same platform. So we will update that as we learn more.

是的，沒什麼要補充的了。我的意思是，我們正在繼續與監管機構討論該項目的具體內容，以及它如何像疫苗研發那樣，加快藥物研發進程，使其比使用相同平台開發的第一代藥物所需的時間更長。我們會隨著了解更多資訊而更新相關資訊。

George, there's some confusion, just so you could clarify it. Our next-generation antibody work on just -- Omicron on is a work on all of them.

喬治，這裡有些誤解，你來澄清一下。我們下一代抗體的研究——Omicron——是針對所有這些抗體的。

Yes, George, go ahead.

好的，喬治，請繼續。

As I mentioned in my script, so obviously, we have one of the largest collections of antibodies to choose from. And what we do as a variant emerges is we select new candidate antibodies that will work against the new variant, but will also retain their activity against the previous variants of concern. And that's exactly the candidates that we're advancing right now. They work against Omicron, but they work against Delta. They work against all the other variants before. .

正如我在稿子裡提到的，我們擁有數量龐大的抗體庫可供選擇。當出現新的變異株時，我們會篩選出新的候選抗體，這些抗體不僅能對抗新的變異株，還能維持對先前關注的變異株的活性。而這正是我們目前正在推進的候選抗體。它們不僅對奧密克戎變異株有效，而且對德爾塔變異株也有效，對先前所有的變異株都有效。

And anything -- any comment on stealth Omicron, do you think it will work there, too?

還有什麼要說的嗎？關於隱形版的歐米克隆號，你覺得它在那裡也能發揮作用嗎？

Well, yes. Obviously, we take all these things into consideration. And so when a new variant that looks like it could be coming along that might be important, we certainly have made sure that the candidates that we're advancing now are going to be active against all of those as well.

是的，我們當然會把所有這些因素都考慮在內。因此，當出現一種可能很重要的新變種時，我們一定會確保我們目前正在推進的候選疫苗也能有效對抗所有這些變種。

Our next question comes from Salveen Richter with Goldman Sachs.

下一個問題來自高盛的薩爾文·里希特。

Could you just speak to the RNAi programs? I think we're going to get first data this year from ALN-APP from that program. And how do you think about the optimization of delivery to the brain here and what we might see and how the C5 program could be differentiated?

您能談談RNAi計畫嗎？我認為我們今年會從該專案的ALN-APP中獲得第一批數據。您認為如何優化藥物向大腦的遞送，我們可能會看到什麼結果，以及C5計畫如何脫穎而出？

Okay. So you're asking about the brain and CNS and the APP program, but you're always asking about C5. Okay.

好的。所以你問的是大腦、中樞神經系統和APP程序，但你總是問C5。好的。

So yes, with the brain, obviously, as we all know, there have been disappointing results with antibodies that have been delivered to try to decrease APP levels. They work in a fundamentally different way.

是的，就大腦而言，顯然，我們都知道，用抗體降低APP水平的嘗試結果令人失望。它們的作用機製本質上是不同的。

One of the problems that they cause, they cause the famous inflammatory syndrome that may complicate activity. So obviously, the hope of siRNA programs is they work by a completely different mechanism.

它們造成的問題之一是會引發著名的發炎綜合徵，這可能會使治療活動變得複雜。因此，siRNA療法的希望顯然在於它們的作用機製完全不同。

They will actually decrease the production of APP and allowed to be cleared by normal mechanisms as opposed to letting it be made continuously at the normal rate and then trying to remove it by artificial mechanisms that they themselves may be toxic, i.e., the antibody efforts. So that's why they may be fundamentally different.

實際上，它們會降低APP的生成，並允許其透過正常機制清除，而不是像抗體療法那樣，讓APP以正常速率持續生成，然後試圖透過可能本身就具有毒性的人工機制將其清除。所以，這就是它們本質上可能存在差異的原因。

Importantly, we're exploring this not only in Alzheimer's disease, as we all know. It's not as if the early results in Alzheimer's disease are going to really address the important endpoints, that is cognition and efficacy in slowing down cognitive decline and so forth. They're going to be looking at levels of biomarkers and so forth.

重要的是，我們不僅在阿茲海默症領域探索這一主題，正如我們所知。阿茲海默症早期研究結果並不能真正解決重要的終點指標，例如認知功能以及延緩認知衰退的療效等等。他們主要關注的是生物標誌物的水平等等。

That's why we're also excited that we are developing the same exact agent, in some ways, a much more rapidly progressing, though albeit much rare disease known as cerebral amyloid angiopathy, or CAA, because there, the ability to both look at the biomarkers, but also, more importantly, look at important efficacy parameters is going to allow us to proceed much faster and much smaller numbers of patients.

正因如此，我們也對正在開發同一種藥物感到興奮，這種藥物在某些方面用於治療一種進展更快、雖然罕見得多的疾病，即腦澱粉樣血管病（CAA）。因為在CAA中，我們既可以觀察生物標記，更重要的是，還可以觀察重要的療效參數，這將使我們能夠更快地推進治療，並減少患者的數量。

And therein, we may be, over the next couple of years, able to establish both definitive efficacy, but maybe even get authorization approved in those indications, and that will certainly be quite in advance for the entire field of these types of diseases, and particularly for the first siRNA that's going into these diseases.

因此，在接下來的幾年裡，我們或許能夠確定其確切療效，甚至可能獲得這些適應症的批准，這對於這類疾病的整個領域來說，尤其是對於第一個用於治療這些疾病的 siRNA 而言，無疑是相當領先的。

So we are very excited about these programs, and we have a very large pipeline of other CNS diseases and targets that we are going forward in addressing with Alnylam.

因此，我們對這些項目感到非常興奮，我們還有非常龐大的其他中樞神經系統疾病和靶點研發管線，我們將與 Alnylam 一起推進這些研發。

So it's a very important part of our collaborative efforts with them, which also include a large number of targets in terms of genetic targets, genetically validated targets,and diseases in the eye, let alone outside of the eye such as, for example, in the liver, and that brings us to the C5 that you asked about.

因此，這是我們與他們合作中非常重要的一部分，其中還包括大量的基因靶點、基因驗證靶點以及眼部疾病，更不用說眼部以外的疾病，例如肝臟疾病，這就引出了你提到的 C5。

So as we all know, people are taking single types of approaches to target C5. Some people might have an antibody. There's now some other types of approaches and so forth.

眾所周知，目前人們針對C5的治療方法各不相同。有些人可能已經產生了抗體。現在還有其他一些治療方法等等。

What we realized is that if we could combine an siRNA with an antibody, we might have really not only combine the unique advantages of both, but incredible synergies.

我們意識到，如果我們能將siRNA與抗體結合起來，我們不僅可以真正結合兩者的獨特優勢，而且還能產生不可思議的協同效應。

And what do we mean? Antibodies have the highest effectiveness because, essentially, they can bring down activity levels almost to 0. But because of the high target load, you have to give these antibodies, and these are all the existing approved antibodies and those that are under investigation by other sponsors, you have to give them a relatively large amount of them and relatively frequently.

這是什麼意思呢？抗體之所以療效最高，是因為它們基本上可以將活性水平降低到幾乎為零。但由於標靶細胞負荷高，你必須給患者註射這些抗體——包括所有已獲批准的抗體以及其他申辦者正在研究的抗體——而且必須注射相對較大劑量、相對頻繁的抗體。

So antibodies are great. But by themselves, you need to give a lot of antibodies to deal with a high target load. siRNAs are great at reducing the target load, but they don't get you to really almost 0 activity, and that creates problems.

所以抗體固然很好，但單靠抗體本身，你需要大量的抗體才能應付高水準的標靶。 siRNA 能有效降低標靶載量，但它們無法將活性降至幾乎為零，這會帶來一些問題。

We already know that. By putting the 2 together, you now get the best of both. You reduce the target load, and you allow now a much smaller amount of antibody to control activity hopefully completely.

我們早就知道這一點。將兩者結合起來，就能兼得二者之長。既能降低標靶負荷，又能使少量抗體就足以完全控制活性。

So there really is tremendous synergy with this. This is the first of its kind that is combining siRNA with antibodies. We think there's very exciting potential for this to deliver best-in-class, both efficacy but also convenience and dosing regimen.

因此，這確實具有巨大的協同效應。這是第一個將siRNA與抗體結合的療法。我們認為它具有非常令人興奮的潛力，預計在療效、便利性和給藥方案方面都達到一流水平。

We're going for convenient subcutaneous self-administration once a month, which would really, I think, be game changing for the field and for these patients. But we're also moving these programs also to other related indications as well.

我們正在探索每月一次便捷的皮下自我給藥方式，我認為這將真正改變該領域和這些患者的治療現狀。同時，我們也正在將這些項目推廣到其他相關適應症領域。

So we're very excited about this combination approach for C5 and for these types of indications. But once again, just like what we're doing in CNS, just like what we're doing with eye, these are really franchise and portfolio opportunities.

因此，我們對C5的這種聯合療法以及針對這些適應症的療法感到非常興奮。但再次強調，就像我們在中樞神經系統和眼科領域所做的那樣，這些都是真正的特許經營和產品組合機會。

I mean, you can just imagine, if combining -- and there are so many other settings where this could be very useful, combining the benefits of siRNA and antibodies and bringing them together could really begin changing not only in this area, but in many, many other areas. And who better to do this than bringing together the leading siRNA company and the leading antibody and biologics company, Alnylam and Regeneron.

我的意思是，你可以想像一下，如果將siRNA和抗體結合起來——而且在許多其他領域，這種結合也非常有用——它們的優勢結合起來，不僅能在這個領域，還能在許多其他領域帶來真正的變革。還有誰比領先的siRNA公司Alnylam和領先的抗體及生物製劑公司Regeneron更適合做這件事呢？

So we are very excited about the individual programs with some of these siRNA, but also these incredible combination opportunities, bringing these 2 incredible technologies together, taking the advantages of both.

因此，我們對其中一些 siRNA 的個別項目感到非常興奮，同時也對這些令人難以置信的組合機會感到非常興奮，將這兩種令人難以置信的技術結合起來，發揮兩者的優勢。

Our next question comes from Ronny Gal with Alliance Bernstein.

我們的下一個問題來自 Alliance Bernstein 的 Ronny Gal。

One is for Marion. Can you talk a little bit about the VEGF market? It seems that we've been coming close to a year for a better than 10% growth. And I was wondering how much of this is catch-up versus how much of this is just higher natural market growth rate versus what we're expecting.

一個問題問的是Marion。您能談談VEGF市場嗎？我們似乎已經連續近一年維持了超過10%的成長。我想知道這其中有多少是市場追趕效應，又有多少是因為天然市場成長率高於預期。

And then can you talk a little bit about the dynamics of what it takes to compete in this market, kind of like how long to get a J code, how long to have contract with different practices? Essentially, when will -- how long will take a competitor coming online, whether innovative or biosimilar, to really be able to effectively compete in that market?

那麼，您能否談談在這個市場競爭所需的各種因素，例如獲得J代碼需要多長時間，與不同診所簽訂合約需要多長時間？本質上來說，無論是創新藥還是生物類似藥，競爭對手上線後需要多長時間才能真正有效參與市場競爭？

Sure. Ronny, happy to take it, and I'm going to take the end of your question first.

當然可以。羅尼，我很樂意回答，我先回答你問題的後半部。

And I first would say that a competitor or a new entrant to the market's ability to compete is really going to be based on the differentiation of their product profile, the quality of their studies and the confidence and enthusiasm that the key opinion leaders have on the product as it comes in. So I do think differentiation matters quite a lot.

首先，我認為競爭對手或新進業者能否在市場上競爭，真正取決於其產品定位的差異化、研究品質以及關鍵意見領袖對產品的信心和熱情。所以我認為差異化至關重要。

In the case of EYLEA, certainly, our growth in the past year has been quite pronounced. We've captured not only the market growth, but we've also captured competitive share gain more than any other products, so that our market share today for EYLEA is approaching 50% of the overall category and 75% of the branded category. And we picked up several share points in the last year in this very large category.

就安怡而言，過去一年我們的成長確實非常顯著。我們不僅抓住了市場成長機會，而且在競爭中也取得了比其他任何產品都更高的市佔率成長，目前安怡的市佔率已接近整個品類的50%，品牌品類的75%。在過去一年裡，我們在這個龐大的品類中獲得了相當可觀的市佔率。

Let me go back now to new entrants. You're asking about timing of J codes, and that is important. Quality of product, as I mentioned, reflects confidence in how well it performs, but it is a 6-month period before a new product receives a permanent J code.

現在讓我回到新入行者的話題。你們問到了J程式碼的審核時間，這很重要。正如我之前提到的，產品品質反映了人們對其性能的信心，但新產品需要6個月的時間才能獲得永久的J代碼。

So in that window of time, especially in a product which is buy and bill, there's always the concern on reimbursement. There's not experience, not with the product, but there's also not experience with applying for reimbursement under the J-code. That period of time is 6 months. And to my earlier comment, product confidence will vary based on profile.

因此，在這段時間裡，尤其對於先購買後付款的產品，報銷問題始終令人擔憂。他們既缺乏產品使用經驗，也缺乏透過J代碼申請報銷的經驗。這段時間長達6個月。至於我之前提到的，產品信心會因個人情況而有所不同。

I hope I've covered, Ronny, most of what you had in that. The only thing I think I probably missed is anti-VEGF category growth going forward. That is a little bit complicated because we're comparing to recovery in the market opposite the COVID period to some extent. However, there is growth of the category because of patient demographics and because of education.

羅尼，我希望我已經涵蓋了你剛才提到的大部分內容。我唯一可能遺漏的是抗VEGF藥物未來的成長前景。這有點複雜，因為我們在某種程度上是在與新冠疫情期間市場復甦的情況進行比較。然而，由於患者群體結構的變化和教育水平的提高，該藥物類別確實在增長。

I'll give you an example of patients who are diagnosed with DME, only about 47%, 48% of those patients are treated. And those are -- and of those that are diagnosed, there's only -- if you took all DME patients that exist, only about 25% of those patients are treated.

我舉個例子，在被診斷出患有糖尿病性黃斑水腫（DME）的患者中，只有大約47%到48%的患者接受了治療。而這些患者──如果把所有患有DME的患者都算在內，只有大約25%的患者接受了治療。

So there still is tremendous unmet need in the marketplace, and we certainly will work hard through educational initiatives to make sure that we perform very well as we have been on an ongoing basis on all of our indications. I hope that helps, Ronny.

因此，市場上仍然存在巨大的未滿足需求，我們一定會透過教育推廣活動努力工作，確保我們在所有適應症方面都能像以往一樣取得優異成績。希望這對您有所幫助，羅尼。

Can I just add one thing, Ronny, on that? It's just that it seems like it's been every single year for the last decade there has been a threat to EYLEA that a variety of number of people have predicted would be the next thing to displace EYLEA.

羅尼，我可以補充一點嗎？是說，在過去十年裡，似乎每年都會有各種各樣的人預測EYLEA會受到威脅，而這些威脅將會取代EYLEA。

And along the way, the barriers have changed. And the most important barrier that I think now exists is safety, and that safety, even for a biosimilar, the same product safety for a new product with purported differences, people have learned that the eye is a very sensitive place.

在過程中，障礙也發生了變化。我認為現在最重要的障礙是安全性，即使是生物類似藥，或者與聲稱有差異的新產品一樣，人們也已經認識到眼睛是一個非常敏感的部位。

And having given scores of millions of injections of EYLEA, there's a great deal of confidence out there. I think it's going to take a matter of time beyond J codes and meeting with practices before that level of confidence is significantly displaced.

由於已經注射了數千萬劑愛樂疫苗，人們對它充滿信心。我認為，除了J代碼的實施和與臨床實踐的溝通之外，還需要一段時間，這種信心才會顯著減弱。

Our next question comes from Robyn Karnauskas with Truist.

下一個問題來自 Truist 的 Robyn Karnauskas。

This is Nicole on for Robyn. Just a really quick question on yesterday's report, the Adicet Bio disclosing their general exercising option to license an allo CAR-T. Can you just comment on the move towards allo CAR-T and why this particular happened?

這裡是妮可，替羅賓發言。關於昨天報道中提到的Adicet Bio公司宣布行使授權選擇權，獲得異基因CAR-T療法許可的消息，我有一個簡短的問題。您能否談談他們轉向異基因CAR-T療法的原因？

Could you repeat the end of the question? It was a little hard to hear the question.

您能再說一次問題的結尾嗎？我剛才有點聽不清楚問題。

The Adicet?

阿迪塞特？

Yes. But what was the question? Can you repeat it?

是的。但是問題是什麼來著？你能再說一次嗎？

Why does that matter? What's the importance of it?

這為什麼重要？它的意義何在？

So well, as you already referred to it, I mean, this is an advance in the CAR-T space because, obviously, so far, the approved approach and upcoming approaches are all dependent on giving customized individualized autologous CAR-T cells.

正如您剛才提到的，這可以說是 CAR-T 領域的進步，因為顯然，到目前為止，已批准的方法和即將推出的方法都依賴於提供客製化的個體化自體 CAR-T 細胞。

And the results coming from this relatively novel gamma delta approach is the first gamma delta data in the world show that you could give allogeneic cells and get very remarkable -- in very small numbers, a very remarkable response rate.

而這種相對較新的伽瑪德爾方法的結果是，世界上第一個伽瑪德爾數據表明，即使使用同種異體細胞，也能獲得非常顯著的——即使數量很少，也具有非常顯著的反應率。

And so this would take the customization autologous approach and take it to the autologous to the non-autologous allogeneic way, which will really could potentially revolutionize the treatment paradigm here. And so we've been long-term collaborators with Adicet, and we're pretty excited about this allogeneic approach. And so we're investing in it.

因此，這將把自體移植的個人化治療方案擴展到非自體異體移植，這有可能徹底改變目前的治療模式。我們與Adicet公司一直保持著長期的合作關係，我們對這種異體移植方案感到非常興奮，因此我們正在對其進行投資。

Our next question comes from Matthew Harrison with Morgan Stanley.

下一個問題來自摩根士丹利的馬修·哈里森。

I was hoping for one on co-stim. I know we're supposed to get some data this year. Can you just maybe help us think about dosing levels, how you're thinking about safety currently?

我原本希望能得到一些關於聯合刺激劑的數據。我知道今年應該會有一些數據公佈。您能否幫我們考慮一下劑量水平，以及您目前是如何看待安全性的？

And just in terms of initial data, what should we expect to see, whether it's just about safety or we should really start to have some idea on efficacy as well?

就初步數據而言，我們應該期待看到什麼？是僅僅關於安全性，還是我們也應該開始對療效有所了解？

Yes. That's a great question. And as we all know, this pathway was explored many years ago now and led to, unfortunately, very dramatic safety concerns to patients, and that sort of killed the field.

是的，這是一個很好的問題。我們都知道，這條途徑多年前就有人探索過，但不幸的是，它給患者帶來了非常嚴重的安全隱患，也因此扼殺了這個領域。

And so because of those concerns and that we were reexploring utilization of this very, very powerful co-stimulatory pathway to add to -- in combination with other immunotherapies, the FDA appropriately asked us to move very, very slowly.

因此，由於這些擔憂，以及我們正在重新探索利用這個非常非常強大的共刺激路徑來增強其他免疫療法，FDA 要求我們非常非常緩慢地前進，這是理所當然的。

So the first endpoint of most concern was the safety endpoint, of course, first do no harm. And I think that what we've announced is that in our ongoing dose escalation study, it's only been recently that we have achieved what we think are therapeutic dose potential levels.

因此，首要關注的終點當然是安全性終點，首先要確保不造成傷害。我認為我們已經宣布的是，在我們正在進行的劑量遞增研究中，我們最近才達到我們認為具有治療潛力的劑量水平。

And now -- and we have -- I think the thing that we have said publicly is we successfully crossed in terms of getting to these dose levels, this very concerning and potentially game stopping safety hurdles. And so now that we're at the potentially therapeutic dose levels, we are now hoping to focus on efficacy.

現在——正如我們公開宣布的那樣——我們已經成功克服了這些令人擔憂、甚至可能導致專案停滯的安全障礙，達到了目前的劑量水平。既然我們已經達到了潛在的治療劑量水平，我們現在希望將重點放在療效上。

And remember, in several of these programs, for example, our prostate program, we're going in a setting where, at least if properly identified, there are essentially no or very rare responses to PD-1 in these types of very carefully characterized prostate patients. I mean, there has been very little hope, except for rare subsets of characterized patients that have mutations and so forth, for the PD-1 immunotherapy class.

請記住，在某些項目中，例如我們的前列腺癌項目，我們面對的是這樣的情況：至少在正確識別的情況下，對於這類經過嚴格篩選的前列腺癌患者，PD-1 療法幾乎沒有或完全無效。我的意思是，除了少數攜帶特定基因突變等特徵的患者亞群外，PD-1 免疫療法幾乎沒有其他希望。

So if we can show essentially almost any responses in these types of very recalcitrant and hard-to-treat patients with PD-1 alone in our combinations with our co-stim for prostate cancer, I think there's real reason to believe that our scientists have successfully figured out a completely novel way of taking advantage of this long known, very exciting and powerful, but dangerous pathway that we may have figured out a way to take advantage of it and done it in a safe manner.

因此，如果我們能夠證明，對於這類頑固難治的前列腺癌患者，單獨使用 PD-1 聯合我們的前列腺癌共刺激療法幾乎可以產生任何反應，我認為我們有充分的理由相信，我們的科學家已經成功地找到了一種全新的方法來利用這條早已為人所知、非常令人興奮和強大，但也很危險的通路，我們可能已經找到了一種利用它的方法，並且是以安全的方式進行的。

So this is what we're hoping to see this year that now that we are at these levels, we've gotten there without activating these huge safety concerns that were previously seeing. Essentially seeing any objective responses in this setting would really be potentially game changing. And so we're looking forward to being able to tell you about this possibility later this year.

所以，我們希望今年能夠看到，在達到目前的水平後，我們能夠避免之前出現的那些巨大的安全隱患。在這種情況下，任何客觀的回饋都將具有顛覆性的潛力。因此，我們期待今年稍後能與大家分享這方面的可能性。

Our next question comes from Cory Kasimov with JPMorgan.

下一個問題來自摩根大通的科里·卡西莫夫。

Wondering if you could frame expectations for the pending update on your program with Intellia that we're getting here near term. What new might we see relative to last summer's preliminary data disclosure?

想請您談談近期即將發布的關於您與Intellia合作項目的最新進展，以及我們可能會看到哪些新內容，與去年夏天公佈的初步數據相比？

Yes. We don't want to get too far in front of our partner. George's remarks already indicated the kind of things we'll see, but we should leave it up to Intellia to comment beyond what George said about looking at the dose escalation and including the safety and knockdown of the TTR. But Intellia should have the benefit of making some comments.

是的。我們不想搶在合作夥伴前面太遠。喬治的演講已經暗示了我們將會看到的內容，但我們應該讓Intellia公司就喬治提到的劑量遞增、安全性以及TTR的抑製作用等問題發表更多評論。不過，Intellia公司應該有機會發表一些看法。

But maybe just a couple of obvious points that's not stealing anybody's thunder. But obviously, the initial results were incredibly exciting and revolutionary.

但或許有幾點顯而易見，並不會引起太多關注。但很顯然，最初的結果令人無比興奮，具有革命性意義。

Obviously, the first systemic case CRISPR therapy, I mean, all this excitement for almost 20 years, Nobel prizes and all this, I mean, it is incredible that, together with our Intellia colleagues, I mean, this represents the first-ever systemic use of CRISPR to actually modify human genetic gene.

顯然，這是首例係統性 CRISPR 療法，我的意思是，近 20 年來，人們為此感到無比興奮，獲得了諾貝爾獎等等，我的意思是，令人難以置信的是，我們與 Intellia 的同事們一起，這代表了 CRISPR 首次系統性地用於真正修改人類基因。

But obviously, one of the most important things that one will see is the whole promise of this approach is duration, that is you are modifying the gene. And hopefully, you will never have to treat that patient again, okay? And that's part of the dream and the hope with these genetic cures.

但很顯然，這種方法最重要的優點之一在於其持久性，也就是說，它能改變基因。希望以後患者無需再接受治療，對吧？這正是基因療法的夢想和希望。

And so this is, of course, one important thing that we hope that we'll be seeing from the follow-up data, the duration, which is what is really game changing. You can permanently cure these patients. That's the theory here by permanently changing their genes.

所以，我們希望從後續數據中看到的一個重要訊息就是療效持續時間，而這才是真正具有改變意義的。理論上講，透過永久性地改變患者的基因，就可以永久治癒他們。

And so the longer you follow them up, the more you can validate the duration with, of course, the appropriate safety and continue to keep the dream alive that this whole new approach could really be game-changing for important and appropriate clinical indications.

因此，你追蹤的時間越長，就越能驗證其持續時間，當然也要確保其安全性，並繼續保持這樣的夢想：這種全新的方法對於重要的、合適的臨床適應症來說，真的可以帶來改變。

Our last question comes from Mohit Bansal with Wells Fargo.

最後一個問題來自富國銀行的莫希特·班薩爾。

And congrats on the progress. Maybe another one on faricimab. And given that your competitor also has Lucentis, which is facing biosimilar this year, are you seeing any rumblings of potential bundling or attractive pricing for those both products combined, that could be played as a strategy to take on EYLEA? And how much does payer versus provider matter in this market?

恭喜取得進展。或許可以再談談法瑞西單抗（faricimab）？鑑於您的競爭對手也有盧森蒂斯（Lucentis），而盧森蒂斯今年將面臨生物相似藥的競爭，您是否注意到任何關於這兩款產品捆綁銷售或推出優惠定價的傳聞，這或許可以作為對抗安永（EYLEA）的策略？在這個市場中，支付方和醫療服務提供者之間的差異有多大？

Sure. So at a high level, I'll share just and talk about our own business is, certainly, we have strong market understanding and work closely with all of our customers across the market segments. When it comes to how another company might be looking at their pricing or strategy, it's probably best I let them comment. But I appreciate the interest in the category and the question.

當然。那麼，我先概括地談談我們自身的業務。我們當然對市場有著深刻的理解，並與各個細分市場的客戶保持著密切的合作。至於其他公司如何看待他們的定價或策略，最好還是讓他們自己來評論。但我很感謝您對這個領域的關注和提出的問題。

Thanks, everyone. That concludes today's conference call, and thanks for your interest in Regeneron. The IR team and Bob Landry is here to take any questions that you may have. Everyone, have a nice day.

謝謝大家。今天的電話會議到此結束，感謝各位對Regeneron的關注。投資者關係團隊和Bob Landry將在此回答大家可能提出的任何問題。祝大家今天愉快。

This concludes the program. You may now disconnect.

程式到此結束，您可以斷開連線了。