輝瑞 (PFE) 2021 Q4 法說會逐字稿

Good day, everyone, and welcome to Pfizer's Fourth Quarter 2021 Earnings Conference Call. Today's call is being recorded.

大家好，歡迎參加輝瑞公司 2021 年第四季度收益電話會議。今天的電話正在錄音。

At this time, I would like to turn the call over to Mr. Chris Stevo, Senior Vice President and Chief Investor Relations Officer. Please go ahead, sir.

此時，我想將電話轉給高級副總裁兼首席投資者關係官 Chris Stevo 先生。請繼續，先生。

Thank you, Sylvia. Good morning, everyone. Welcome to Pfizer's Fourth Quarter Earnings Call. I'm joined today by Dr. Albert Bourla, our Chairman and CEO; Frank D'Amelio, our CFO; Mikael Dolsten, President, Worldwide Research and Development and Medical; Angela Hwang, Group President, Pfizer Biopharmaceuticals Group; Aamir Malik, our Chief Business and Innovation Officer; and Doug Lankler, our General Counsel. We expect this call to last 90 minutes.

謝謝你，西爾維亞。大家，早安。歡迎來到輝瑞公司第四季度財報電話會議。今天，我們的董事長兼首席執行官 Albert Bourla 博士加入了我的行列；我們的首席財務官 Frank D'Amelio； Mikael Dolsten，全球研發和醫療總裁；輝瑞生物製藥集團總裁Angela Hwang； Aamir Malik，我們的首席業務和創新官；和我們的總法律顧問 Doug Lankler。我們預計此通話將持續 90 分鐘。

The materials for this call and other earnings-related materials are on the Investor Relations section of Pfizer.com. Please see our forward-looking statements disclaimer on Slide 3. And additional information regarding these statements and our non-GAAP financial measures is available on our earnings release and in our SEC Forms 10-K and 10-Q under Risk Factors. Forward-looking statements on the call are subject to substantial risks and uncertainties, speak only as of the call's original date, and we undertake no obligation to update or revise any of these statements.

本次電話會議的材料和其他與收益相關的材料位於 Pfizer.com 的投資者關係部分。請參閱我們在幻燈片 3 上的前瞻性聲明免責聲明。有關這些聲明和我們的非公認會計原則財務指標的更多信息可在我們的收益發布和我們的風險因素下的 SEC 10-K 和 10-Q 表格中獲得。關於電話會議的前瞻性陳述受到重大風險和不確定性的影響，僅在電話會議的原始日期發表，我們不承擔更新或修改任何這些陳述的義務。

With that, I will turn the call over to Albert.

有了這個，我會把電話轉給阿爾伯特。

Thank you, Chris. Hello, everyone.

謝謝你，克里斯。大家好。

2021 was a watershed year for Pfizer, a year in which we set all-time highs in all major areas of focus for Pfizer. We reached an estimated 1.4 billion patients with our medicines and vaccines. That's more than 1 out of every 6 people on earth. Never before has Pfizer's patient impact been so wide reaching.

2021 年是輝瑞公司的分水嶺，這一年我們在輝瑞公司的所有主要關注領域都創下歷史新高。估計有 14 億患者使用我們的藥物和疫苗。這超過了地球上每 6 個人中的 1 個。輝瑞對患者的影響從未如此廣泛。

We improved our ranking from fourth to second among large biopharma companies in the PatientView Global Survey. According to Morning Consult, 61% of Americans have a favorable view of Pfizer, which is up 33 points since January of 2020. Just last week, Fortune ranked us 4th on its annual World's Most Admired Companies list, the highest ranking we have ever achieved. 95% of our colleagues said in an internal survey that they are proud to work for Pfizer, which ranks among the best in corporate America. We increased our investments in research and development from $8.9 billion in 2020 to $10.5 billion in 2021, and we initiated 13 pivotal clinical studies, the highest number ever for Pfizer. Last but not least, we grew revenues by 92% operationally to $81.3 billion and Adjusted diluted EPS by 92% operationally to $4.42.

在 PatientView 全球調查中，我們在大型生物製藥公司中的排名從第四位提高到第二位。根據 Morning Consult 的數據，61% 的美國人對輝瑞（Pfizer）有好感，自 2020 年 1 月以來上升了 33 個百分點。就在上週，《財富》雜誌在其年度全球最受尊敬公司排行榜中將我們排名第四，這是我們有史以來的最高排名.我們 95% 的同事在一項內部調查中表示，他們為為輝瑞工作而感到自豪，輝瑞在美國企業界名列前茅。我們將研發投資從 2020 年的 89 億美元增加到 2021 年的 105 億美元，我們啟動了 13 項關鍵臨床研究，這是輝瑞有史以來的最高數字。最後但同樣重要的是，我們的運營收入增長了 92%，達到 813 億美元，調整後的攤薄後每股收益增長了 92%，達到 4.42 美元。

Our success in leading the fight against COVID-19 have not only made a positive difference in the world. I believe they have fundamentally changed our company and our culture forever. Colleagues across Pfizer are inspired by what we have achieved and most are more determined than ever to be part of the next potentially game-changing breakthrough. To that end, we are applying the Lightspeed principles developed for our COVID-19 work to our other therapeutic areas to make sure we continue to move at the speed of science for the benefits of all patients.

我們在領導與 COVID-19 的鬥爭中取得的成功不僅對世界產生了積極影響。我相信他們從根本上永遠改變了我們的公司和我們的文化。輝瑞的同事受到我們所取得的成就的啟發，並且大多數人比以往任何時候都更加堅定地成為下一個可能改變遊戲規則的突破的一部分。為此，我們正在將針對 COVID-19 工作開發的 Lightspeed 原則應用於我們的其他治療領域，以確保我們繼續以科學的速度前進，以造福所有患者。

As a result, we believe we can do even better with each of these metrics in 2022, each one of them. Our full year 2022 financial guidance, for example, includes, for the first time ever, a forecasted revenue midpoint, that it is triple digit, $100 billion, and an Adjusted diluted EPS midpoint of $6.45.

因此，我們相信，到 2022 年，我們可以在這些指標中的每一個指標上做得更好。例如，我們的 2022 年全年財務指導首次包括預測收入中點，即三位數，1000 億美元，調整後的稀釋後每股收益中點為 6.45 美元。

While Comirnaty is having a significant positive impact on Pfizer's financial performance, it is the tremendous impact that COVID-19 vaccines have had on society that it is most important. In the U.S. alone, the COVID-19 vaccination program is estimated to have saved more than 1 million lives and prevented more than 10 million hospitalizations, according to a December 2021 Commonwealth Fund report.

儘管 Comirnaty 對輝瑞的財務業績產生了重大的積極影響，但最重要的是 COVID-19 疫苗對社會產生的巨大影響。根據聯邦基金 2021 年 12 月的一份報告，僅在美國，COVID-19 疫苗接種計劃估計就挽救了超過 100 萬人的生命並防止了超過 1000 萬人住院。

The economic impact is equally astonishing, astounding. According to December 2021 Heartland Forward report, the rapid deployment and wide availability of COVID-19 vaccines in the U.S. created an estimated economic savings of $438 billion in 2021 alone, which amounted to U.S. GDP being 2.3% higher than it otherwise would have been, 2.3 points.

經濟影響同樣驚人，令人震驚。根據 2021 年 12 月的 Heartland Forward 報告，僅在 2021 年，美國迅速部署和廣泛使用 COVID-19 疫苗就創造了 4,380 億美元的經濟節省，這相當於美國 GDP 比其他情況下高出 2.3%， 2.3 分。

I'm proud to say that Pfizer contributed significantly to these benefits, given that approximately 6 out of 10 doses administered in the U.S. as of February 6, 2022, were Comirnaty. This is the value of our science, what our culture has enabled and what drives our people.

我很自豪地說，輝瑞對這些益處做出了重大貢獻，因為截至 2022 年 2 月 6 日，在美國施用的 10 劑中約有 6 劑是 Comirnaty。這是我們科學的價值，是我們的文化所促成的，也是我們人民的動力。

Now I would like to speak to 3 factors that will help drive our growth going forward. The first is the long-term outlook for COVID-19 and why we believe we are well positioned to continue to lead the battle against this disease. Second, our thoughtful capital allocation strategy and why we believe it can help drive our growth in the second part of the decade. And third, how our commitment to ESG principles is designed to create sustainable growth for Pfizer to deliver meaningful value to patients and society.

現在，我想談談有助於推動我們向前發展的 3 個因素。首先是 COVID-19 的長期前景，以及為什麼我們認為我們有能力繼續領導與這種疾病的鬥爭。其次，我們深思熟慮的資本配置策略以及為什麼我們相信它可以幫助推動我們在本世紀後半段的增長。第三，我們對 ESG 原則的承諾如何旨在為輝瑞創造可持續增長，從而為患者和社會提供有意義的價值。

Let me start with the COVID-19 pandemic. Our scientists continue to monitor the SARS-CoV-2 virus and believe it is unlikely that it will be fully eradicated in the foreseeable future. They believe this for several reasons. The global distribution of the virus makes it difficult to contain. The virus has shown an ability to mutate often, making it difficult to stay ahead of it. And the data appear to show that natural infections do not lead to the type of durable protection needed to prevent all transmissions and viral mutations. As a result, people can become reinfected by the same or different strains over time.

讓我從 COVID-19 大流行開始。我們的科學家繼續監測 SARS-CoV-2 病毒，並認為在可預見的未來它不太可能被完全根除。他們相信這一點有幾個原因。該病毒的全球分佈使其難以遏制。該病毒已顯示出經常變異的能力，因此很難保持領先。數據似乎表明，自然感染不會導致防止所有傳播和病毒突變所需的持久保護類型。因此，隨著時間的推移，人們可能會再次感染相同或不同的菌株。

That said, we now have the tools in the form of vaccines and treatments, that we believe will help enable us to not only better manage the pandemic, but also help countries move into an endemic phase. In other words, we believe these tools will help us allow us to go back to normality and spend time with family and friends, travel, attend indoor dining and concerts and enjoy many other activities, while lowering the risk of overburdening hospitals and health care systems around the world.

也就是說，我們現在擁有疫苗和治療形式的工具，我們相信這將有助於我們不僅能夠更好地管理這一流行病，而且還有助於各國進入流行階段。換句話說，我們相信這些工具將幫助我們恢復正常生活，與家人和朋友共度時光、旅行、參加室內用餐和音樂會以及享受許多其他活動，同時降低醫院和醫療保健系統負擔過重的風險世界各地。

All of us at Pfizer are extremely proud of the role we have continued to play in bringing these tools to the world. Throughout 2021, we continued our efforts to bring our COVID-19 vaccine to more populations and to further ramp up our manufacturing and distribution capabilities. As a result, the market share of our Comirnaty vaccine has continued to grow, representing 70% of all doses distributed across the U.S. and EU as of February 5.

輝瑞的所有人都為我們在將這些工具推向世界方面繼續發揮的作用感到非常自豪。在整個 2021 年，我們繼續努力將我們的 COVID-19 疫苗帶給更多人群，並進一步提高我們的製造和分銷能力。因此，我們的 Comirnaty 疫苗的市場份額持續增長，截至 2 月 5 日，占美國和歐盟分發的所有劑量的 70%。

When it comes to Paxlovid, we expect to produce 6 million treatment courses during the first quarter of '22. Overall, we expect to produce 30 million courses in the first half of 2022 and 120 million courses for the full year, of course, depending on the global need. Having recently received a conditional marketing authorization from the European Medicines Agency, Paxlovid has now received emergency or conditional authorization for use with certain populations in approximately 40 countries so far. We are in discussions with governments around the world and expect that as the number of authorizations increase, so will the number of contracts for this treatment, which could truly be a game changer.

談到 Paxlovid，我們預計在 22 年第一季度將生產 600 萬個療程。總體而言，我們預計 2022 年上半年將生產 3000 萬門課程，全年生產 1.2 億門課程，當然，這取決於全球需求。 Paxlovid 最近獲得了歐洲藥品管理局的有條件上市許可，目前已獲得緊急或有條件授權，可在約 40 個國家/地區的某些人群中使用。我們正在與世界各地的政府進行討論，並預計隨著授權數量的增加，這種治療的合同數量也會增加，這可能會真正改變遊戲規則。

At Pfizer, we are keenly aware of our responsibility to continue to invest in R&D to maintain our leadership in providing these tools and other meaningful solutions to the world. That's why we continue to develop and test different versions of our vaccine to potentially address variants of concern as they emerge, and why we are currently working on a new Omicron-based vaccine candidate and on a bivalent COVID-19 vaccine candidate. It is also why just 2 months after receiving Emergency Use Authorization from the U.S. Food and Drug Administration for Paxlovid, we are already working on a potential next-generation oral COVID-19 treatment. Going forward, we are confident in our ability to maintain this leadership position because of our significant investments in R&D; combined with our ability to move at the speed of science without compromising quality or safety; the strong credibility we have earned with governments, health care providers and consumers; combined with our extensive global field presence and our unparalleled capabilities for high-quality manufacturing at scale.

在輝瑞，我們敏銳地意識到我們有責任繼續投資於研發，以保持我們在向世界提供這些工具和其他有意義的解決方案方面的領導地位。這就是為什麼我們繼續開發和測試不同版本的疫苗以潛在地解決出現的關注變體，以及為什麼我們目前正在研究一種新的基於 Omicron 的候選疫苗和一種二價 COVID-19 候選疫苗。這也是為什麼在獲得美國食品和藥物管理局對 Paxlovid 的緊急使用授權僅 2 個月後，我們就已經在研究一種潛在的下一代口服 COVID-19 治療方法。展望未來，由於我們在研發方面的大量投資，我們對保持這一領先地位的能力充滿信心；結合我們在不影響質量或安全的情況下以科學的速度前進的能力；我們在政府、醫療保健提供者和消費者中贏得的強大信譽；結合我們廣泛的全球現場存在和我們無與倫比的大規模高質量製造能力。

Now the second thing I wanted to touch on is how we think about our capital allocation and to repeat once more our strategy. We feel that the entirety of our business continues to demonstrate a robust top line growth trajectory through 2025. Consensus estimates are beginning to slowly recognize this momentum. However, consensus estimates currently saw our top line shrinking from 2025 to 2030. I want to repeat that this is inconsistent with our own plans. Our goal is to continue to be a growth company from '25 to 2030, despite the impact of LOEs expected during that period.

現在我想談的第二件事是我們如何看待我們的資本分配並再次重複我們的策略。我們認為，到 2025 年，我們的整個業務繼續展現出強勁的收入增長軌跡。共識估計開始慢慢認識到這一勢頭。然而，目前的共識估計顯示，我們的收入從 2025 年到 2030 年會萎縮。我想重申，這與我們自己的計劃不一致。我們的目標是從 25 年到 2030 年繼續成為一家成長型公司，儘管在此期間預計會受到 LOE 的影響。

Our confidence in our ability to achieve that is underpinned by the momentum of our business, the durability of our COVID-19 offerings, which as I just described, the underestimated strength of our internal pipeline; and of course, by our ability to deploy capital into growth-focused business development to access external science.

我們對實現這一目標的能力充滿信心，這得益於我們業務的發展勢頭、我們 COVID-19 產品的耐用性，正如我剛才所描述的，我們內部管道的實力被低估了；當然，通過我們將資本部署到以增長為重點的業務發展以獲取外部科學的能力。

A few words about that. We leverage business development opportunities to advance our business strategies and objectives. The strength of our balance sheet and cash flows allows us to pursue new business development opportunities going forward that could add at least $25 billion of risk-adjusted revenues to our 2030 top line expectations. We expect to do this while still maintaining our growing dividend as well as flexibility for other uses of our cash.

說幾句。我們利用業務發展機會來推進我們的業務戰略和目標。我們的資產負債表和現金流的實力使我們能夠尋求新的業務發展機會，這可以為我們的 2030 年收入預期增加至少 250 億美元的風險調整收入。我們希望在保持增長的股息以及現金其他用途的靈活性的同時做到這一點。

The focus of our business development efforts will continue to be on compelling external science in the form of both later-stage assets as well as earlier medical innovations that have the potential to be breakthroughs for patients. Our focus will largely be in the therapeutic areas and platforms where we have the scientific skills and acumen to add substantial value and select the most successful targets. In addition, we feel that we have distinctive attributes, such as world-class excellence in clinical development and unsurpassed manufacturing and commercial capabilities at scale that makes us a very attractive partner across a variety of deal arrangements. We believe the opportunities to deliver on this approach exist, and I will be personally focusing on this execution.

我們業務發展工作的重點將繼續放在以後期資產和早期醫療創新的形式引人注目的外部科學上，這些創新有可能成為患者的突破口。我們的重點將主要集中在我們擁有科學技能和敏銳度的治療領域和平台，以增加實質性價值並選擇最成功的目標。此外，我們認為我們具有獨特的屬性，例如世界級的卓越臨床開發和無與倫比的大規模製造和商業能力，這使我們成為各種交易安排中非常有吸引力的合作夥伴。我們相信實現這種方法的機會是存在的，我個人將專注於這種執行。

I want to emphasize that despite our significant capital flexibility, we will never lower the scientific and financial standards we apply in our business development. As we pursue these opportunities, we will continue to be highly disciplined in our evaluation and prioritization processes.

我想強調的是，儘管我們有很大的資本靈活性，但我們永遠不會降低我們在業務發展中應用的科學和財務標準。在我們追求這些機會的同時，我們將繼續在評估和優先排序過程中保持高度紀律。

Since 2019, we have already invested almost $25 billion in business development transactions, adding more than $13 billion in consensus, I repeat, in consensus 2030 revenue. I would point out that the $13 billion of consensus currently includes nothing for the Trillium assets, the Biohaven collaboration or the recently announced mRNA deals, all of which have substantial potential. I see this pace of business development accelerating going forward, and I'm confident it will be an important driver in ensuring Pfizer as a growth company in the back half of this decade.

自 2019 年以來，我們已經在業務發展交易上投資了近 250 億美元，我重複一遍，在 2030 年的共識收入中增加了超過 130 億美元的共識。我要指出的是，目前 130 億美元的共識不包括 Trillium 資產、Biohaven 合作或最近宣布的 mRNA 交易，所有這些都具有巨大的潛力。我看到這種業務發展的步伐正在加快，我相信這將成為確保輝瑞在本世紀後半期成為一家成長型公司的重要驅動力。

One highly visible example of our approach to business development is the recent investments we are making in mRNA technology and collaborations. mRNA has emerged as a versatile technology with potential application across many infectious diseases, cancer, rare genetic disorders and even autoimmune diseases. Although mRNA is not the holy grail, we believe the technology has the potential to have a game-changing impact on global health, which is why we have developed a robust mRNA strategy and are aggressively building our platform.

我們的業務發展方法的一個非常明顯的例子是我們最近在 mRNA 技術和合作方面的投資。 mRNA 已成為一種多功能技術，在許多傳染病、癌症、罕見遺傳疾病甚至自身免疫疾病中都有潛在的應用。儘管 mRNA 不是聖杯，但我們相信該技術有可能對全球健康產生改變遊戲規則的影響，這就是我們制定強大的 mRNA 戰略並積極構建我們平台的原因。

While the pandemic has demonstrated that it is not that easy to deliver mRNA vaccines at scale, Pfizer has emerged as a leader in this space. With decades of experience on our side, we have developed what is arguably the most efficient clinical development and vaccine manufacturing capabilities the world has ever seen. We also have rapidly scaled and built out new capabilities in record time by hiring nearly 2,400 new colleagues in these functions in a 9-month time frame. Going forward, we plan to continue to invest to capitalize on the leadership we have built in terms of both mRNA R&D and manufacturing.

雖然大流行表明大規模提供 mRNA 疫苗並不容易，但輝瑞已成為該領域的領導者。憑藉我們數十年的經驗，我們已經開發出可以說是世界上最有效的臨床開發和疫苗製造能力。我們還通過在 9 個月的時間框架內聘用了近 2,400 名新同事從事這些職能，從而在創紀錄的時間內迅速擴展並建立了新的能力。展望未來，我們計劃繼續投資，以利用我們在 mRNA 研發和製造方面建立的領導地位。

In addition, of course, to these internal investments and improvements, we are also making external investments to build out our capabilities in this space. For example, Pfizer recently has entered into 4 important business development deals to help advance our mRNA strategy. We are expanding our collaboration with BioNTech to use the existing platform to co-develop an mRNA vaccine candidate for herpes zoster virus to protect against shingles.

當然，除了這些內部投資和改進之外，我們還在進行外部投資以增強我們在這一領域的能力。例如，輝瑞最近達成了 4 項重要的業務發展交易，以幫助推進我們的 mRNA 戰略。我們正在擴大與 BioNTech 的合作，利用現有平台共同開發一種針對帶狀皰疹病毒的 mRNA 候選疫苗，以預防帶狀皰疹。

Our agreement with Beam Therapeutics expands our mRNA efforts to another core therapeutic area for Pfizer, the rare disease, with a 4-year research collaboration for 3 targets for rare genetic diseases of the liver, muscle and central nervous system. We believe this will give us the potential to use mRNA to treat diseases, not just prevent them.

我們與 Beam Therapeutics 達成的協議將我們的 mRNA 工作擴大到輝瑞公司的另一個核心治療領域，即罕見病，與針對肝臟、肌肉和中樞神經系統罕見遺傳疾病的 3 個靶點進行為期 4 年的研究合作。我們相信這將使我們有可能使用 mRNA 來治療疾病，而不僅僅是預防疾病。

Our agreement with Acuitas gives us the ability to collaborate with and license their proprietary lipid nanoparticle technology for up to 10 targets for mRNA vaccines and therapy. We believe this will give us greater independence in this space. And we have signed a strategic collaboration and licensing agreement with Codex DNA, a leader in the development of automated solutions for on-demand synthesis of genes and mRNA, potentially allowing enzymatic assembly of DNA at the front end of the mRNA production process. This could possibly reduce the time to produce a new vaccine from 3 months down to 2 months. If successful, this would be an important differentiator when developing a vaccine for the flu, for example, as it would allow us to select a strain much closer to the start of any flu season.

我們與 Acuitas 的協議使我們能夠與他們的專有脂質納米顆粒技術合作並獲得許可，用於 mRNA 疫苗和治療的多達 10 個目標。我們相信這將使我們在這個領域擁有更大的獨立性。我們還與 Codex DNA 簽署了戰略合作和許可協議，Codex DNA 是開發基因和 mRNA 按需合成自動化解決方案的領導者，可能允許在 mRNA 生產過程的前端進行 DNA 酶促組裝。這可能會將生產新疫苗的時間從 3 個月縮短到 2 個月。例如，如果成功，這將是開發流感疫苗時的一個重要區別，因為它可以讓我們選擇更接近任何流感季節開始的毒株。

These deals represent only 4 pieces of a much bigger strategic puzzle. As we continue executing on our mRNA strategy, you should expect to see more targeted activity in this area.

這些交易僅代表了一個更大的戰略難題的 4 個部分。隨著我們繼續執行我們的 mRNA 戰略，您應該期望在該領域看到更多有針對性的活動。

Of course, our business development activity in the last quarter went beyond executing on our mRNA strategy. This is an update of the slide I showed you last quarter, and I would like to highlight a few of the other recent deals. They are marked as new in this slide.

當然，我們上一季度的業務發展活動超出了我們 mRNA 戰略的執行範圍。這是我上個季度向您展示的幻燈片的更新，我想重點介紹其他一些最近的交易。它們在這張幻燈片中被標記為新的。

The acquisition of Trillium builds on our strong track record of leadership in oncology, enhancing our hematology portfolio as we strive to improve outcomes for people living with blood cancers around the globe. Our strategic collaboration with Biohaven leverages our leading commercial capabilities in pain and in women's health.

收購 Trillium 建立在我們在腫瘤學領域的良好領導記錄的基礎上，增強了我們的血液學產品組合，因為我們努力改善全球血癌患者的預後。我們與 Biohaven 的戰略合作利用了我們在疼痛和女性健康方面領先的商業能力。

(technical difficulty)

（技術難度）

I apologize. We're back. I apologize for the technical issue. I will repeat my script for this last slide, and then we go forward.

我道歉。我們回來了。我為技術問題道歉。我將為最後一張幻燈片重複我的腳本，然後我們繼續。

So of course, our business development activity in the last quarter went beyond executing on our mRNA strategy. This is an update of the slide I showed you last quarter, and I would like to highlight a few of the other recent deals. You can see them with the indication of new.

因此，我們上一季度的業務發展活動當然超出了我們的 mRNA 戰略的執行範圍。這是我上個季度向您展示的幻燈片的更新，我想重點介紹其他一些最近的交易。您可以看到它們帶有新的指示。

The acquisition of Trillium builds on our strong track record of leadership in oncology, enhancing our hematology portfolio as we strive to improve outcomes for people living with blood cancers around the globe. Our strategic collaboration with Biohaven leverages our leading commercial capabilities in pain and women's health, with Biohaven's groundbreaking oral CGRP receptor antagonist, the only one approved in the U.S. for both acute and preventative treatment of migraine, so that we can potentially bring a valuable new treatment option to patients living with this debilitating neurological disease outside the U.S.

收購 Trillium 建立在我們在腫瘤學領域的良好領導記錄的基礎上，增強了我們的血液學產品組合，因為我們努力改善全球血癌患者的預後。我們與 Biohaven 的戰略合作利用了我們在疼痛和女性健康方面領先的商業能力，以及 Biohaven 的突破性口服 CGRP 受體拮抗劑，這是美國唯一獲批用於偏頭痛急性和預防性治療的藥物，因此我們有可能帶來有價值的新療法美國以外患有這種使人衰弱的神經系統疾病的患者的選擇

And through our proposed acquisition of Arena, we plan to leverage Pfizer's leading research and global development capabilities to accelerate the clinical development of etrasimod for patients with immuno-inflammatory diseases.

通過我們對 Arena 的擬議收購，我們計劃利用輝瑞領先的研究和全球開發能力來加速 etrasimod 用於免疫炎症性疾病患者的臨床開發。

Now I would like to share some details about Pfizer's enhanced ESG strategy. The strategy is focused on 6 areas where we see opportunities to create a meaningful and measurable impact over the next decade: product innovation, equitable access and pricing, product quality and safety; diversity, equity and inclusion; climate change and business ethics.

現在我想分享一些關于輝瑞強化 ESG 戰略的細節。該戰略側重於我們認為有機會在未來十年內產生有意義和可衡量影響的 6 個領域：產品創新、公平獲取和定價、產品質量和安全；多樣性、公平性和包容性；氣候變化和商業道德。

Each quarter going forward, I will provide examples of how we are embedding ESG into all core areas of our business. This quarter, I would highlight our efforts to improve clinical trial diversity, to improve diversity within our colleague base and help ensure equitable access to our COVID-19 vaccine and treatment.

今後每個季度，我都會舉例說明我們如何將 ESG 嵌入我們業務的所有核心領域。本季度，我將強調我們為改善臨床試驗多樣性、改善我們同事群體的多樣性以及幫助確保公平獲得我們的 COVID-19 疫苗和治療所做的努力。

Last year, Pfizer published an industry-first retrospective analysis of demographic data of U.S. participants in 213 of our interventional clinical trials that initiated enrollment from 2011 through 2020. The analysis demonstrated that overall trial participation of Black or African American individuals was at the U.S. census level, 14.3% versus 13.4%; participation of Hispanic or Latino individuals was below U.S. census, 15.9% versus 18.5%; and female participation was at U.S. census, 51.1% versus 50.8%.

去年，輝瑞（Pfizer）在 2011 年至 2020 年開始招募的 213 項介入性臨床試驗中，對美國參與者的人口統計數據進行了業界首創的回顧性分析。分析表明，黑人或非裔美國人的總體試驗參與情況在美國人口普查中水平，14.3% 對 13.4%；西班牙裔或拉丁裔個人的參與率低於美國人口普查，分別為 15.9% 和 18.5%；在美國人口普查中，女性參與率分別為 51.1% 和 50.8%。

We published this analysis to be transparent and for it to serve as the baseline as we measure progress in this area. We believe that diversity in trials is a matter of equity and good science and are taking decisive steps designed to improve diversity in our trials. Our goal is to achieve racially and ethnically diverse participation at or above U.S. census or disease prevalence levels, as appropriate, in all our trials.

我們發布此分析是為了透明，並將其作為我們衡量該領域進展的基準。我們認為，試驗中的多樣性是公平和良好科學的問題，並且正在採取旨在改善試驗多樣性的決定性步驟。我們的目標是在我們所有的試驗中，酌情在美國人口普查或疾病流行水平或以上實現種族和族裔多元化參與。

The second item I want to highlight is the significant progress we are making in diversifying our colleague base, particularly at more senior-level positions. In the last 3 years, for example, we have increased the percentage of women at the vice president level and above globally from 32% to 42%. Over the same time frame, we have increased the percentage of minorities at the vice president level and above in the U.S. from 19% to 25%.

我想強調的第二個項目是我們在使我們的同事基礎多樣化方面取得的重大進展，特別是在更高級別的職位上。例如，在過去 3 年中，我們將全球副總裁及以上級別的女性比例從 32% 提高到了 42%。在同一時間範圍內，我們將美國副總統及以上級別的少數族裔比例從 19% 提高到 25%。

The third item I wanted to highlight is the progress we are making to help ensure our COVID-19 vaccine and oral treatment are accessible by everyone everywhere. I am thrilled to say that we remain on track to meet or exceed our global -- our goal of delivering at least 2 billion doses of our vaccine to low and middle-income countries by the end of 2022, having just met our goal of delivering the first 1 billion by the end of 2021.

我想強調的第三個項目是我們正在取得的進展，以幫助確保世界各地的每個人都能獲得我們的 COVID-19 疫苗和口服治療。我很高興地說，我們仍有望達到或超過我們的全球目標——我們的目標是到 2022 年底向低收入和中等收入國家提供至少 20 億劑疫苗，剛剛實現了我們的目標到 2021 年底前 10 億。

I also want to highlight 2 data points about our 2 billion dose commitment. One billion of these doses are being provided to the poorest countries completely free of charge. Thanks to our agreement with the U.S. government, Pfizer is providing these doses to the U.S. government at a not-for-profit price, and the government is then providing them to the poorest countries for free. Also, the 1 billion doses we delivered in 2021 represented 37% of all doses we delivered this last year.

我還想強調關於我們 20 億劑承諾的 2 個數據點。其中 10 億劑完全免費提供給最貧窮的國家。由於我們與美國政府達成的協議，輝瑞公司以非營利性價格向美國政府提供這些劑量，然後政府將這些劑量免費提供給最貧窮的國家。此外，我們在 2021 年交付的 10 億劑疫苗占我們去年交付的所有劑量的 37%。

In terms of our oral COVID-19 treatment, we have signed a voluntary license agreement with the Medicines Patent Pool, which we hope will lead to expanded access, pending country regulatory authorization or approval, in 95 low- and middle-income countries that account for approximately 53% of the world population. Lastly, I'm pleased to announce that the Compensation Committee of our Board of Directors has been reviewing methods for linking executive compensation with ESG performance, which we expect to begin this year. For details regarding the impact of our ESG strategy had on our business in 2021, please keep an eye out for Pfizer's 2021 ESG report, which will be published online in mid-March.

在我們的口服 COVID-19 治療方面，我們已與藥品專利池簽署了一項自願許可協議，我們希望該協議將在 95 個中低收入國家擴大使用範圍，等待國家監管授權或批准約佔世界人口的 53%。最後，我很高興地宣布，我們董事會的薪酬委員會一直在審查將高管薪酬與 ESG 績效掛鉤的方法，我們預計將於今年開始。關於我們ESG戰略對我們2021年業務的影響，請關注輝瑞將於3月中旬在線發布的2021年ESG報告。

In summary, 2021 was an outstanding year for Pfizer, and we look forward to continuing to apply the lessons learned from COVID-19 to deliver breakthroughs for patients across all our therapeutic areas. We remain focused on being nimble, investing in our R&D organization and exploring dynamic partnerships that will enable us to fully realize the power of our science.

總而言之，2021 年對輝瑞來說是傑出的一年，我們期待繼續應用從 COVID-19 中吸取的教訓，為我們所有治療領域的患者帶來突破。我們仍然專注於保持敏捷，投資於我們的研發組織並探索動態的合作夥伴關係，這將使我們能夠充分認識到我們科學的力量。

None of this is possible without the contributions of our amazingly purpose-driven colleagues, who continue to rise to the challenge of addressing the world's most devastating diseases. In 2021, our colleagues exceeded expectations. Therefore, we will once again use part of the bonus pool that the Board approved for bonus-eligible colleagues and executives to provide a onetime, special COVID-19 Circumstances Bonus to our non-bonus-eligible colleagues across the board to reward them for their hard work and to help them cover personal, family and living expenses incurred because of the COVID-19 pandemic.

如果沒有我們以驚人的目標為導向的同事的貢獻，這一切都是不可能的，他們繼續迎接挑戰，解決世界上最具破壞性的疾病。 2021 年，我們的同事超出了預期。因此，我們將再次使用董事會為符合獎金條件的同事和高管批准的部分獎金池，為我們所有不符合獎金條件的同事提供一次性的特殊 COVID-19 情況獎金，以獎勵他們努力工作，並幫助他們支付因 COVID-19 大流行而產生的個人、家庭和生活費用。

With that, I will turn it over to Mikael to update you on our R&D efforts. After Mikael, Frank will provide financial details on the fourth quarter and our outlook for 2022. So, Mikael?

有了這個，我將把它交給 Mikael 向您介紹我們的研發工作。在 Mikael 之後，Frank 將提供第四季度的財務細節以及我們對 2022 年的展望。那麼，Mikael 呢？

Thank you, Albert. I'm delighted to share updates from this quarter as we continue to deliver first-in-class science. Today, I will share updates from our COVID-19 programs and select other assets in our pipeline. Let's start with Paxlovid.

謝謝你，阿爾伯特。隨著我們繼續提供一流的科學，我很高興分享本季度的更新。今天，我將分享我們 COVID-19 計劃的更新，並選擇我們管道中的其他資產。讓我們從 Paxlovid 開始。

As the COVID-19 pandemic continues to burden public health, we have advanced the science on our novel oral antiviral therapeutics. Importantly, we see consistent, potent antiviral activity in vitro against all current variants of concern, including both Delta and Omicron.

隨著 COVID-19 大流行繼續給公共衛生帶來負擔，我們推進了新型口服抗病毒療法的科學發展。重要的是，我們在體外看到了針對所有當前關注的變體（包括 Delta 和 Omicron）的一致、有效的抗病毒活性。

This would be expected from how the compound was designed. On the left, you can see a crystal structure showing how tightly nirmatrelvir binds to the active site of the Omicron variant. History has told us from the HIV protease field that the closer the therapeutic is designed to mimic the substrate, the harder it is for resistance to emerge. That, combined with the essential nature of the protease, the short duration of treatment and the co-dosing with ritonavir to drug exposures that are over 5 to 6x the amount of compound needed to kill the virus in an in vitro assay, suggest there is reduced risk for resistance.

從化合物的設計方式可以預料到這一點。在左側，您可以看到一個晶體結構，顯示 nirmatrelvir 與 Omicron 變體的活性位點結合的緊密程度。歷史從 HIV 蛋白酶領域告訴我們，治療方法設計得越接近於模擬底物，就越難產生抗藥性。結合蛋白酶的基本性質、治療時間短以及與利托那韋共同給藥的藥物暴露量是體外試驗中殺死病毒所需的化合物量的 5 至 6 倍以上，表明存在降低抗藥性的風險。

External data support our findings. In this slide, the lower values, the stronger potency, illustrated by nirmatrelvir being on the lower end of the Y axis on the left, having the most potent activity. Nirmatrelvir maintains in vitro potency in the low nanomolar range, as you can see in these graphs that include other authorized or approved therapeutics.

外部數據支持我們的發現。在這張幻燈片中，值越低，效力越強，尼馬特雷韋位於左側 Y 軸的下端，具有最強的活性。 Nirmatrelvir 在低納摩爾範圍內保持體外效力，正如您在這些圖表中看到的那樣，這些圖表包括其他授權或批准的治療方法。

On the left is in vitro data from a study done with the Icahn School of Medicine at Mount Sinai and Pfizer. Nirmatrelvir demonstrated potent antiviral activity, as measured by IC50, a measure of drug efficacy indicating the concentration needed to inhibit infection by half. This is consistent with findings from the Rega Institute at KU Leuven in Belgium, shown on the right.

左邊是來自西奈山伊坎醫學院和輝瑞公司的一項研究的體外數據。 Nirmatrelvir 顯示出有效的抗病毒活性，通過 IC50 測量，IC50 是一種藥物功效的量度，表明將感染抑制一半所需的濃度。這與比利時魯汶大學雷加研究所的研究結果一致，如右圖所示。

We anticipate a New Drug Application decision by the FDA in the high-risk population in second half of '22; pivotal readouts of our household contact and standard-risk studies in the second quarter and second half of '22, respectively; and the study start in children 6 to 18 years old in the first quarter of '22. In the standard-risk study, we're expanding enrollment by 750 non-hospitalized patients with symptomatic COVID-19, and vaccinated standard-risk patients may also be eligible, provided their last SARS-CoV-2 vaccine dose was received at least 12 months prior to screening. This expansion will allow us to further evaluate the secondary end points seen in the interim analysis, which showed a 70% reduction in hospitalization and no death in the treated compared to placebo.

我們預計 FDA 將在 22 年下半年對高危人群做出新藥申請決定；分別在 22 年第二季度和下半年我們的家庭接觸和標準風險研究的關鍵讀數；該研究於 22 年第一季度開始在 6 至 18 歲的兒童中進行。在標準風險研究中，我們正在擴大 750 名有症狀的 COVID-19 未住院患者的招募範圍，並且接種了標準風險疫苗的標準風險患者也可能符合條件，前提是他們最後一次 SARS-CoV-2 疫苗接種至少 12放映前幾個月。這種擴展將使我們能夠進一步評估中期分析中看到的次要終點，與安慰劑相比，治療組的住院率降低了 70%，並且沒有死亡。

We also are advancing work on a potential next-generation SARS-CoV-2 antiviral with the aim of achieving similar high clinical efficacy in pan-coronavirus design properties that maintain activity with a favorable safety profile and counter potential viral resistance, but without the need for ritonavir boosting. A first in human study is expected in the second half of '22.

我們還在推進一種潛在的下一代 SARS-CoV-2 抗病毒藥物的工作，目的是在泛冠狀病毒設計特性方面實現類似的高臨床療效，以良好的安全性和對抗潛在的病毒耐藥性保持活性，但不需要用於利托那韋升壓。預計 22 年下半年將首次進行人體研究。

Now we also continue to advance vaccine development and have achieved Emergency Use Authorization for use in children as young as age 5. Effectiveness data for 3 doses of the vaccine for 12 -- people 12 years and older, and early laboratory data observed with Delta and other variants of concern, including Omicron, suggest that people vaccinated with 3 doses of Comirnaty may have a higher degree of protection against both symptomatic and severe outcomes compared to 2 primary doses.

現在，我們還繼續推進疫苗開發，並已獲得用於 5 歲以下兒童的緊急使用授權。 12 人（12 歲及以上）的 3 劑疫苗的有效性數據，以及與 Delta 和 Delta 觀察到的早期實驗室數據其他令人擔憂的變體，包括 Omicron，表明接種 3 劑 Comirnaty 疫苗的人與 2 次主要劑量相比，可能對症狀和嚴重後果具有更高程度的保護。

Informed by this data, in addition to the immuno-bridging data, we are evaluating a third 3-microgram dose in our study of children 6 months through 4 years of age, with the belief that a third dose may be optimal for this age group. However, as pediatric cases and hospitalization are at an all-time high, FDA urged us to start a rolling EUA authorization submission with the 2-dose efficacy, immunogenicity and safety data we have accumulated thus far, while we continue to collect data, including on third-dose administration. We plan to submit third-dose data once they're available.

根據這些數據，除了免疫橋接數據外，我們正在對 6 個月至 4 歲兒童的研究中評估第三劑 3 微克劑量，相信第三劑可能是該年齡組的最佳劑量.然而，由於兒科病例和住院人數處於歷史最高水平，FDA 敦促我們開始滾動 EUA 授權提交，其中包含我們迄今為止積累的 2 劑療效、免疫原性和安全性數據，同時我們繼續收集數據，包括關於第三劑給藥。我們計劃在第三劑數據可用後提交。

In the meantime, FDA has scheduled an Advisory Committee meeting for February 15 to consider the 2-dose pediatric data collected today. If Emergency Use Authorization of 2 doses is granted and the CDC recommends usage, parents will have the opportunity to begin a COVID-19 vaccination series for their children between 6 months and 4 years of age, while awaiting potential authorization of a third dose.

與此同時，FDA 已安排在 2 月 15 日召開諮詢委員會會議，以審議今天收集的 2 劑兒科數據。如果授予 2 劑緊急使用授權並且 CDC 建議使用，父母將有機會為 6 個月至 4 歲的孩子開始 COVID-19 疫苗系列，同時等待第三劑的潛在授權。

Turning to the adult population. In the wake of surging Omicron cases, in January, we completed a lab analysis of the effect of a third dose boost of Comirnaty on live virus neutralization. Encouragingly, there was a more than 25-fold increase in Omicron live virus neutralization titers observed between day of dose 3 and 1 month post-dose 3. We observed a moderate 4-month post-dose 3 antibody decay for wild type and the Omicron variant. Between 1 month and 4 months post-dose 3, neutralizing titers were at 1.6 and twofold lower for wild type and the Omicron, respectively.

轉向成年人口。在 Omicron 病例激增之後，我們在 1 月份完成了對 Comirnaty 第三劑加強對活病毒中和的影響的實驗室分析。令人鼓舞的是，在給藥 3 天和給藥 3 後 1 個月之間觀察到 Omicron 活病毒中和滴度增加了 25 倍以上。我們觀察到野生型和 Omicron 的 4 個月後劑量 3 抗體適度衰減變體。在第 3 次給藥後 1 個月和 4 個月之間，野生型和 Omicron 的中和效價分別低 1.6 和兩倍。

We're now starting to see effects of a third dose boost in maintaining a high level of protection against Omicron in the real world. These data from Kaiser Permanente Southern California show Omicron-related emergency department visits without hospitalization on top and hospitalization on the bottom. Three doses of Comirnaty provided better vaccine effectiveness against Omicron than 2 doses. And there was high vaccine effectiveness of 3 doses against Omicron-related hospitalization, similar to Delta-related hospitalization. We did see some waning of effectiveness against emergency department admissions due to Omicron 3 months or more after third dose, which suggest the potential need for another boost of the current vaccine or an Omicron-based vaccine.

我們現在開始看到在現實世界中保持對 Omicron 的高水平保護方面的第三次劑量提升的效果。這些來自南加州 Kaiser Permanente 的數據顯示了與 Omicron 相關的急診科就診次數，頂部未住院，底部未住院。與 2 劑相比，3 劑 Comirnaty 對 Omicron 的疫苗效果更好。並且有 3 劑疫苗對 Omicron 相關住院治療的有效性很高，類似於 Delta 相關住院治療。我們確實看到由於 Omicron 在第三劑疫苗後 3 個月或更長時間對急診科入院的有效性有所減弱，這表明可能需要再次加強當前的疫苗或基於 Omicron 的疫苗。

We have started an Omicron-based vaccine candidate trial in adults 18 to 55 years of age. This study will evaluate more than 1,400 participants across 3 cohorts. Those who have already received 2 doses of the current vaccine 90 to 180 days prior to enrollment will receive 1 or 2 doses of the based Omicron-based vaccine. Those who have already received 3 doses of the current vaccine 90 to 180 days prior to enrollment will receive 1 dose of the current vaccine or the Omicron-based vaccine. And those who are vaccine-naive will receive 3 doses of the Omicron-based vaccine. This study is part of our science-based approach to develop a variant-based vaccine that we hope achieves a similar level of protection against Omicron as the current vaccine has with both wild type and earlier variant, but with potentially longer duration of protection.

我們已經在 18 至 55 歲的成年人中開始了一項基於 Omicron 的候選疫苗試驗。這項研究將評估 3 個隊列的 1,400 多名參與者。在入組前 90 至 180 天已接種 2 劑當前疫苗的人將接種 1 劑或 2 劑基於 Omicron 的疫苗。在入組前 90 至 180 天已接種 3 劑當前疫苗的人員將接種 1 劑當前疫苗或基於 Omicron 的疫苗。那些未接種過疫苗的人將接受 3 劑基於 Omicron 的疫苗。這項研究是我們開發基於變體的疫苗的科學方法的一部分，我們希望這種疫苗對 Omicron 的保護水平與當前疫苗對野生型和早期變體的保護水平相似，但可能具有更長的保護持續時間。

Now let's turn to our next-generation CDK inhibitors for cancer. Most patients with advanced or metastatic breast cancer eventually develop resistance to both endocrine and CDK4/6 inhibitor therapy despite their transformative efficacy. Inhibition of CDK2 delivered with a CDK-selective active drug or a triple-active CDK2/4/6 agent may prevent, delay or reverse resistance and prolong survival.

現在讓我們轉向我們的下一代癌症 CDK 抑製劑。大多數晚期或轉移性乳腺癌患者最終都會對內分泌和 CDK4/6 抑製劑治療產生耐藥性，儘管它們具有轉化功效。使用 CDK 選擇性活性藥物或三重活性 CDK2/4/6 藥物抑制 CDK2 可預防、延遲或逆轉耐藥性並延長生存期。

These are data from a subset in the CDK2/4/6 inhibitor Phase 1 dose escalation and antitumor activity study of heavily pretreated patients with hormone receptor positive metastatic breast cancer. The most improvement in terms of tumor size reduction was seen in patients treated with monotherapy or in combination with fulvestrant. We observed 3 confirmed partial responses and 3 patients with stable disease for more than 12 months. One patient has been receiving ongoing treatment for more than 28 months. There's been an acceptable safety profile at the recommended Phase 2 dose, which is 25 milligrams twice daily. We plan to conduct a Phase 1 dose expansion and expect to complete it in the fourth quarter of this year.

這些數據來自 CDK2/4/6 抑製劑 1 期劑量遞增和對激素受體陽性轉移性乳腺癌患者進行大量預處理的抗腫瘤活性研究中的一個子集。單藥治療或與氟維司群聯合治療的患者在腫瘤縮小方面的改善最大。我們觀察到 3 名確認的部分緩解和 3 名病情穩定超過 12 個月的患者。一名患者接受持續治療超過 28 個月。推薦的第 2 階段劑量（每天兩次 25 毫克）具有可接受的安全性。我們計劃進行第一階段的劑量擴展，並預計在今年第四季度完成。

Selective CDK2 inhibition with a CDK2-only inhibitor may allow dose titration and has the potential to be used in combination with approved CDK inhibitors, such as palbociclib or other next-generation CDK selective inhibitors. There were 2 confirmed partial responses in the Phase 1 study of our selective CDK2 inhibitor in patients with advanced or metastatic hormone receptor HER2-negative breast cancer, who had received/progressed on prior CDK4/6 inhibition and endocrine therapy. One patient had a maximum tumor shrinkage of 54% following CDK2 inhibitor treatment for approximately 8 months, and the second had 100% shrinkage of all target lesions following treatment for approximately 9 months.

僅使用 CDK2 抑製劑的選擇性 CDK2 抑制可能允許劑量滴定，並有可能與批准的 CDK 抑製劑聯合使用，例如 palbociclib 或其他下一代 CDK 選擇性抑製劑。在我們的選擇性 CDK2 抑製劑在晚期或轉移性激素受體 HER2 陰性乳腺癌患者中的 1 期研究中確認了 2 項部分反應，這些患者之前接受過/進展了 CDK4/6 抑制和內分泌治療。一名患者在 CDK2 抑製劑治療約 8 個月後最大腫瘤縮小 54%，第二名患者在治療約 9 個月後所有靶病變縮小 100%。

We are showing scans of the first patient at baseline and 8 weeks. There was an acceptable safety profile as a monotherapy, and we're currently exploring combinations. We expect the Phase 1/2 study to be completed in the second quarter of '23.

我們展示了第一位患者在基線和 8 週時的掃描。作為單一療法有可接受的安全性，我們目前正在探索組合。我們預計 1/2 階段研究將在 23 年第二季度完成。

Now let's turn to our 6-valent Lyme disease vaccine candidate, which we are developing in partnership with Valneva. We have received further positive data from our Phase II proof-of-concept study and expect to start Phase 3 in the third quarter of this year with a dosing regimen of 0, 2 and 6 months to prime, followed by routine boosters before the start of a Lyme season. Our Phase 2 studies continue and includes a pediatric population ages 5 to 17 years.

現在讓我們轉向我們正在與 Valneva 合作開發的 6 價萊姆病候選疫苗。我們從我們的 II 期概念驗證研究中獲得了進一步的積極數據，預計將在今年第三季度開始第 3 階段，其給藥方案為 0、2 和 6 個月至啟動期，然後在開始前進行常規加強萊姆季節。我們的 2 期研究仍在繼續，包括 5 至 17 歲的兒科人群。

Since Lyme disease is seasonal, our goal is to establish a regimen that results in high antibodies at the beginning of each season. We therefore looked at a boost 1 year after the primary series. We saw a substantial boost antibody response in Phase II to all 6 serotypes present in North America and Europe following the 3-dose primary series vaccination schedule, with a 14- to 31-fold rise in season 1 and a 51- to 69-fold rise in season 2. The vaccine candidate was generally well tolerated at all dose levels tested, and we are excited about further development and the potential to help prevent this debilitating disease.

由於萊姆病是季節性的，我們的目標是建立一個在每個季節開始時產生高抗體的方案。因此，我們在主要係列賽后 1 年看到了提升。在 3 劑主要係列疫苗接種計劃之後，我們在 II 期看到了對北美和歐洲存在的所有 6 种血清型的顯著增強抗體反應，第 1 季增加了 14 至 31 倍，增加了 51 至 69 倍在第 2 季上升。候選疫苗在所有測試的劑量水平上通常都具有良好的耐受性，我們對進一步的開發和幫助預防這種使人衰弱的疾病的潛力感到興奮。

Last quarter, we told you that we saw robust dystrophin expression out to 1 year in our Duchenne Muscular Dystrophy gene therapy Phase 2b study. I will show you encouraging functional motor data in a moment. We recently shared some very sad news that a DMD patient with advanced disease in the non-ambulatory cohort of the Phase 1b trial passed away after presenting with hypovolemia and cardiogenic shock. The patient was 16 years old and the first in the non-ambulatory cohort treated with Rapamune, along with steroids, as part of the immunosuppressive regimen. Rapamune is not used in the Phase 3 ambulatory study. Like most non-ambulatory DMD patients, he had more advanced disease with underlying cardiac dysfunction. There is evidence of an active viral infection, and we're investigating how this may have contributed to the outcome. Additional assessment will be required to define next steps to restart the Phase 1b study in non-ambulatory patients who are more progressed in the disease.

上個季度，我們告訴您，我們在 Duchenne 肌營養不良症基因治療 2b 期研究中看到了長達 1 年的強健抗肌萎縮蛋白表達。稍後我將向您展示令人鼓舞的功能性運動數據。我們最近分享了一些非常悲傷的消息，即 1b 期試驗的非門診隊列中的一名患有晚期疾病的 DMD 患者在出現低血容量和心源性休克後去世。該患者 16 歲，是第一個接受雷帕明治療的非門診隊列，連同類固醇，作為免疫抑制方案的一部分。 Rapamune 未用於第 3 期門診研究。與大多數非臥床 DMD 患者一樣，他患有更晚期的疾病並伴有潛在的心功能不全。有證據表明存在活躍的病毒感染，我們正在調查這可能如何導致結果。將需要進行額外的評估，以確定在疾病進展較快的非門診患者中重新開始 1b 期研究的下一步。

I will now share data from this study. The ambulatory cohort -- sorry, I had one more sentence to say here. 19 patients were enrolled in this study, 16 of whom received the dose selected for our Phase 3 program, and 3 of whom received a previously studied lower dose. At 1 year post treatment, there was a 5.6-point improvement in ambulatory function, as measured by North Star Ambulatory Assessment, compared to an external control matched for age and baseline function. This is particularly encouraging given that patients at this age and stage of disease typically experience a considerable decline in ambulatory function, as illustrated by the external control.

我現在將分享這項研究的數據。流動隊列——對不起，我在這裡還有一句話要說。 19 名患者參加了這項研究，其中 16 人接受了我們為第 3 期計劃選擇的劑量，其中 3 人接受了先前研究的較低劑量。在治療後 1 年，與年齡和基線功能匹配的外部對照相比，通過北極星動態評估測量的動態功能改善了 5.6 點。這尤其令人鼓舞，因為在這個年齡和疾病階段的患者通常會經歷相當大的行走功能下降，如外部對照所示。

On the right, we show time in study with 6 participants nearing or more than 3 years in treatment. The ambulatory cohort in Phase 1b is similar but slightly older on average to the population in the Phase 3 CIFFREO trial. Considering the favorable benefit-to-risk profile in this study and observed in the ambulatory patient population and in consultation with the Data Monitoring Committee, we believe the safety profile of our DMD gene therapy is manageable in this patient group.

在右側，我們顯示了 6 名參與者接近或超過 3 年的治療時間。 1b 期的門診隊列與 3 期 CIFFREO 試驗中的人群相似，但平均年齡稍大。考慮到本研究中有利的風險收益比以及在門診患者群體中觀察到的情況，並與數據監測委員會協商，我們認為我們的 DMD 基因治療的安全性在該患者群體中是可控的。

Additional mitigation are being added to our study in consultation with eDMC and other medical experts. Pending regulatory feedback, we anticipate Phase III study sites to begin reopen in the next few months, with a potential to report top line results and, subject to clinical trial success, submit a BLA by the end of '23.

在與 eDMC 和其他醫學專家協商後，我們的研究中增加了額外的緩解措施。在等待監管反饋之前，我們預計 III 期研究地點將在未來幾個月內開始重新開放，並有可能報告一線結果，並在臨床試驗成功的情況下，在 23 年底之前提交 BLA。

Turning now to Internal Medicine and ponsegromab, our candidate for cachexia due to cancer. It targets GDF-15. GDF-15 is frequently elevated in cancer patients, drives reduction of appetite and body weight loss and is associated with poor outcomes. There may also be a potential to treat cachexia associated with other chronic diseases, such as heart failure and COPD. We have encouraging Phase 1b data, which I will show next.

現在轉向內科和 ponsegromab，我們因癌症而治療惡病質的候選藥物。它針對 GDF-15。 GDF-15 在癌症患者中經常升高，導致食慾下降和體重減輕，並與不良結果相關。還有可能治療與其他慢性疾病相關的惡病質，例如心力衰竭和慢性阻塞性肺病。我們有令人鼓舞的 1b 階段數據，我將在下面展示。

Ponsegromab was evaluated in 10 cancer patients who are undergoing antitumor treatment and had more than 5% body weight loss in the last 6 months or more than 2% body weight loss with a body mass index of less than 20 kilogram per meter square or diagnosed sarcopenia. Ponsegromab administration was found to suppress circulating GDF-15 levels in cancer cachexia patients, below the level observed in healthy subjects. Preliminary data from the Phase 1b trial show ponsegromab treatment resulted in significant body weight gain compared to historical placebo.

Ponsegromab 在 10 名正在接受抗腫瘤治療且在過去 6 個月內體重減輕超過 5% 或體重減輕超過 2% 且體重指數低於 20 公斤/平方米或被診斷為肌肉減少症的癌症患者中進行了評估.發現 Ponsegromab 給藥可抑制癌症惡病質患者的循環 GDF-15 水平，低於在健康受試者中觀察到的水平。 1b 期試驗的初步數據顯示，與歷史安慰劑相比，ponsegromab 治療導致體重顯著增加。

You can see the nice trend in body weight increase remained even after the dosing was stopped at week 12. The gray dotted line indicates the historical cut-off associated with improved survival. We are co-developing a companion diagnostic with Roche Diagnostics designed to enable precision medicine. And we expect to start the Phase 2 study in cancer cachexia in the fourth quarter of this year.

即使在第 12 週停止給藥後，您仍可以看到體重增加的良好趨勢。灰色虛線表示與提高生存率相關的歷史截止值。我們正在與羅氏診斷共同開發一種伴隨診斷，旨在實現精準醫療。我們預計將在今年第四季度開始癌症惡病質的二期研究。

Injectable GLP-1 receptor agonist offer potent lowering of glucose and weight in diabetic and obese patients with proven cardiovascular benefits, but this drug class is underutilized due to its injectable administration route. Our small molecule oral GLP-1 receptor agonist danuglipron could potentially offer a convenient oral alternative to injectables and is being evaluated for the treatment of type 2 diabetes, obesity and NASH. It has been developed in our Internal Medicine research group with a vision to expand the use of this potent, easily administrated GLP-1 drug class to a primary care setting.

可注射的 GLP-1 受體激動劑可有效降低糖尿病和肥胖患者的血糖和體重，並證明對心血管有益，但由於其可注射給藥途徑，該藥物類別未被充分利用。我們的小分子口服 GLP-1 受體激動劑 danuglipron 可能為註射劑提供一種方便的口服替代品，並且正在評估用於治療 2 型糖尿病、肥胖症和 NASH 的效果。它是在我們的內科研究小組中開發的，旨在將這種強效、易於管理的 GLP-1 藥物類別擴展到初級保健環境。

Here are data from the Phase 2 study in type 2 diabetes. We recorded strong dose-dependent reduction in both HbA1c, a measure of long-term blood sugar levels, and body weight compared to the marginal effect noted with placebo. After 12 weeks of treatment with a 200-milligram twice daily dose, HbA1c decreased by almost 1.6% and body weight decreased by 5.4 kilograms. The safety and tolerability profile is consistent with the GLP-1 class, and the most frequent adverse events were GI-related. We expect to start a Phase IIb titration optimization study mid-'22 with doses up to 200 milligram twice a day and complete the Phase IIb study in nondiabetic subjects with obesity in the first quarter of next year.

以下是 2 型糖尿病 2 期研究的數據。與安慰劑觀察到的邊際效應相比，我們記錄了 HbA1c（一種衡量長期血糖水平的指標）和體重的強烈劑量依賴性降低。每天兩次服用 200 毫克的劑量治療 12 週後，HbA1c 下降了近 1.6%，體重下降了 5.4 公斤。安全性和耐受性與 GLP-1 類一致，最常見的不良事件與 GI 相關。我們預計在 22 年中期開始一項 IIb 期滴定優化研究，每天兩次劑量高達 200 毫克，並在明年第一季度完成對非糖尿病肥胖受試者的 IIb 期研究。

Finally, here are select recent and upcoming milestones from across the pipeline. The solid blue dots represent milestones achieved, and the open blue dots represent anticipated milestones. Programs in bold are major anticipated events. Some of the programs on the right have already been designated as Lightspeed, meaning they have accelerated development time lines or are being considered for Lightspeed designation.

最後，這裡是從整個管道中選擇的最近和即將到來的里程碑。實心藍點代表已實現的里程碑，空心藍點代表預期的里程碑。粗體的節目是重大的預期事件。右邊的一些程序已經被指定為 Lightspeed，這意味著它們已經加快了開發時間線或正在考慮指定 Lightspeed。

Finally, I would like to take a moment to thank Morrie Birnbaum, our outgoing Chief Scientific Officer with the Internal Medicine Research unit, for his immense contribution over the last 7 years. And welcome Bill Sessa, who joins us from Yale School of Medicine, following a decade-long career in academia, including service as Vice Chair of Pharmacology, Professor of Medicine and Director of the Vascular Biology and Therapeutics program at Yale. Bill is an eminent leader in the field, a groundbreaking scientist and a celebrated innovator, and I know he will bring his tremendous vision and insights to our investigation of cardiovascular and metabolic diseases.

最後，我想花一點時間感謝即將離任的內科研究部門首席科學官 Morrie Birnbaum，感謝他在過去 7 年中做出的巨大貢獻。歡迎比爾·塞薩 (Bill Sessa) 從耶魯大學醫學院加入我們，他在學術界工作了十年，包括擔任耶魯大學藥理學副主席、醫學教授和血管生物學和治療學項目主任。比爾是該領域的傑出領導者、開創性的科學家和著名的創新者，我知道他將為我們對心血管和代謝疾病的研究帶來他巨大的遠見和洞察力。

Thank you for your attention. I look forward to your questions. Now let me turn it over to Frank.

感謝您的關注。我期待著你的問題。現在讓我把它交給弗蘭克。

Thanks, Mikael. I know you've seen our release, so let me provide a few highlights regarding the financials. The COVID-19 vaccine, once again, had a positive impact on our quarterly results, and Albert and Mikael have already addressed the key points on the COVID-19 landscape.

謝謝，米凱爾。我知道你已經看過我們的發布，所以讓我提供一些關於財務的亮點。 COVID-19 疫苗再次對我們的季度業績產生了積極影響，Albert 和 Mikael 已經解決了 COVID-19 領域的關鍵問題。

Turning to the income statement. Revenue increased 106% operationally in the fourth quarter of '21, driven by COVID-19 vaccine sales and strong performance from a number of our other key growth drivers. Looking at the revenue, excluding the COVID-19 vaccine direct sales and alliance revenues and Paxlovid contribution, fourth quarter was slower than the first 9 months of the year, declining by 2% operationally. As we discussed during our third quarter call, there was a 4% negative impact or approximately $500 million from fewer selling days in the U.S. and international. Excluding that impact, operational growth would have been 2%, which is still lower than the mid- to high single-digit growth we had experienced during the rest of the year.

轉向損益表。在 COVID-19 疫苗銷售和我們其他一些關鍵增長驅動因素的強勁表現的推動下，21 年第四季度的運營收入增長了 106%。從收入來看，不包括 COVID-19 疫苗直銷和聯盟收入以及 Paxlovid 貢獻，第四季度比今年前 9 個月慢，運營下降 2%。正如我們在第三季度電話會議中所討論的那樣，美國和國際銷售天數減少造成了 4% 的負面影響或約 5 億美元。排除這種影響，運營增長將是 2%，這仍然低於我們在今年剩餘時間經歷的中高個位數增長。

This was factored into our forecast for the year, but let me briefly walk you through this. In our biopharma business, you will remember that the fourth quarter of '21 faced a tough comp from the fourth quarter of 2020 for Prevnar as pneumococcal vaccinations were strong ahead of COVID-19 vaccine availability. Excluding vaccines from the current and comparable period would add 5 percentage points to the growth. Adjusting for the unusual comp period differences related to vaccines and selling days, our revenue growth would have been approximately 7%, which is similar to what we've been delivering lately.

這是我們對今年預測的考慮因素，但讓我簡要介紹一下。在我們的生物製藥業務中，您會記得，與 2020 年第四季度相比，Prevnar 的第四季度面臨著艱難的競爭，因為肺炎球菌疫苗在 COVID-19 疫苗上市之前表現強勁。從當前和可比期間排除疫苗將使增長增加 5 個百分點。調整與疫苗和銷售天數相關的不尋常的補償期差異，我們的收入增長約為 7%，這與我們最近提供的相似。

For the year, operational revenue growth was 92%. Excluding Comirnaty direct sales and alliance revenues and Paxlovid, 2021 operational revenue growth was 6%. This is consistent with our projected revenue CAGR of at least 6% from 2020 through the end of 2025. Of course, there will be some variability in quarterly and annual growth rates due to a variety of factors, but we continue to expect at least a 6% CAGR through 2025.

全年，營業收入增長92%。不包括 Comirnaty 直銷和聯盟收入以及 Paxlovid，2021 年營業收入增長 6%。這與我們預計的從 2020 年到 2025 年底的收入複合年增長率至少為 6% 一致。當然，由於各種因素，季度和年度增長率會有一些變化，但我們繼續預計至少到 2025 年的複合年增長率為 6%。

The adjusted cost of sales increase, shown here, reduced this quarter's gross margin by approximately 16 percentage points compared to the fourth quarter of 2020, which is almost entirely driven by the impact of the COVID-19 vaccine. Adjusted SI&A expenses in the fourth quarter increased primarily due to increased product-level spending, including Comirnaty and higher health care reform sales-based fees. The increase in adjusted R&D expense this quarter was primarily driven by increased investments in late-stage pipeline projects, including additional spending related to our oral COVID-19 treatment.

此處顯示的調整後銷售成本增加使本季度的毛利率與 2020 年第四季度相比降低了約 16 個百分點，這幾乎完全是由 COVID-19 疫苗的影響推動的。第四季度調整後的 SI&A 費用增加主要是由於產品級支出增加，包括 Comirnaty 和更高的醫療改革銷售費用。本季度調整後研發費用的增加主要是由於對後期管道項目的投資增加，包括與我們的口服 COVID-19治療相關的額外支出。

(technical difficulty)

（技術難度）

Frank, I think you were disconnected.

弗蘭克，我想你斷線了。

Yes, we can hear you, Frank. Go ahead.

是的，我們可以聽到你的聲音，弗蘭克。前進。

Okay. I'm not sure where I left off, but I think what I'll do is start with the '22 financial guidance. So we've again provided total company guidance, which includes the business with the COVID-19 vaccine. We will continue to provide insight into our expected revenues for Comirnaty. And now for the first time, we'll also provide some color on our expected revenues for Paxlovid. However, note that we will no longer be providing EPS guidance for the business, excluding Comirnaty. Similarly, we won't provide EPS guidance for Paxlovid.

好的。我不確定我從哪裡停下來，但我認為我要做的是從 '22 財務指導開始。因此，我們再次提供了全面的公司指導，其中包括使用 COVID-19 疫苗的業務。我們將繼續深入了解我們對 Comirnaty 的預期收入。現在，我們還將首次為 Paxlovid 的預期收入提供一些顏色。但是，請注意，我們將不再為該業務提供 EPS 指導，不包括 Comirnaty。同樣，我們不會為 Paxlovid 提供 EPS 指導。

Our revenue guidance represents a record for Pfizer, and we expect total company revenue to be in the range of $98 million to $102 billion, representing an operational growth rate of 24% midpoint. Please consider that this revenue range reflects approximately $1.1 billion of anticipated negative impact from changes in foreign currencies and also the impact of the loss of Meridian sales of approximately $300 million, both of which your models may not take into account.

我們的收入指引是輝瑞公司的創紀錄水平，我們預計公司總收入將在 9800 萬美元至 1020 億美元之間，運營增長率為 24% 的中點。請考慮到這個收入範圍反映了大約 11 億美元的預期負面影響，即外幣變化以及大約 3 億美元的 Meridian 銷售損失的影響，您的模型可能沒有考慮這兩個因素。

Regarding our COVID-related revenues, we now expect the COVID-19 vaccine revenue for the year to be approximately $32 billion, an increase of approximately $1 billion compared to our prior guidance provided on December 17. For Paxlovid, we expect sales of approximately $22 billion. This means that excluding the COVID-related revenues, we expect sales to be $46 billion at the midpoint, representing operational growth of 5%. While this is slightly below the 6% CAGR that we continue to expect between 2020 and 2025, I would remind you that there will be volatility along the way.

關於我們與 COVID 相關的收入，我們現在預計今年 COVID-19 疫苗收入約為 320 億美元，與我們之前在 12 月 17 日提供的指導相比增加了約 10 億美元。對於 Paxlovid，我們預計銷售額約為 22 美元十億。這意味著，不包括與 COVID 相關的收入，我們預計中點銷售額為 460 億美元，運營增長 5%。雖然這略低於我們繼續預期的 2020 年至 2025 年之間 6% 的複合年增長率，但我要提醒您，在此過程中會有波動。

Let me give you some detail on our cost and expense guidance. For Adjusted cost of sales, we are expecting a range of 32.2% to 34.2%. Given that we are now more than 12 months past the launch of Comirnaty, we expect its negative impact on our cost of sales margins to be less than it was in 2021, assuming a similar level of revenues. Further, Paxlovid is expected to have a very positive impact on cost of sales as a percentage of revenues in 2022. On Adjusted SI&A, we expect $12.5 billion to $13.5 billion, an increase of $900 million at the midpoint. We expect our Adjusted R&D guidance range to be $10.5 billion to $11.5 billion at the midpoint, that is about $500 million higher than last year. We expect an Adjusted effective tax rate for the year somewhat higher than 2021 at approximately 16%. These assumptions yield an Adjusted diluted EPS range of $6.35 to $6.55 or 47% operational growth at the midpoint compared to '21, excluding an expected $0.06 negative impact from foreign exchange.

讓我詳細介紹一下我們的成本和費用指南。對於調整後的銷售成本，我們預計範圍為 32.2% 至 34.2%。鑑於我們現在距離 Comirnaty 推出 12 個多月，我們預計其對我們的銷售利潤率成本的負面影響將低於 2021 年，假設收入水平相似。此外，預計 Paxlovid 將對 2022 年銷售成本佔收入的百分比產生非常積極的影響。在調整後的 SI&A 方面，我們預計在 125 億美元至 135 億美元之間，中點增加 9 億美元。我們預計調整後的研髮指導範圍中點為 105 億美元至 115 億美元，比去年高出約 5 億美元。我們預計今年調整後的有效稅率略高於 2021 年，約為 16%。與 21 年相比，這些假設產生了 6.35 美元至 6.55 美元的調整後稀釋每股收益範圍或 47% 的中點運營增長，不包括預期的 0.06 美元來自外彙的負面影響。

I'd like to point out some additional information, which may be helpful for your models. You will note that our guidance assumes a weighted average share count of approximately 5.8 billion, which represents an increase of approximately 100 million shares over 2021. This accounts for the number of shares that we normally issue for employee compensation annually. The increase of 100 million shares over '21 decreases our EPS by about $0.10 at the midpoint. I noticed that most of your models instead assume a flat share count for '22 as compared to '21.

我想指出一些額外的信息，這可能對您的模型有幫助。您會注意到，我們的指導假設加權平均股數約為 58 億股，這意味著比 2021 年增加了約 1 億股。這說明了我們通常每年為員工薪酬而發行的股票數量。 21 年 1 億股的增加使我們的每股收益在中點減少了約 0.10 美元。我注意到，與 '21 相比，您的大多數模型都假設 '22 的份額數量持平。

From the first quarter of '22 and going forward, we've made a decision to modify our Adjusted financials treatment of amortization of intangibles. Previously, we only excluded amortization related to large mergers and acquisitions and exclude all intangible asset amortization expense. This is anticipated to contribute $0.06 to our 2022 Adjusted diluted earnings per share, helps improve comparability with our peers. 2022 guidance once again assumes no share repurchases. We will note that Pfizer did not repurchase shares in either 2020 or 2021. And we continue -- and while we continue to have outstanding unused authorization to repurchase another $5.3 billion of stock, can be opportunistic, given the potentially value-enhancing business development opportunities, which are available to us, we do not expect to repurchase shares in 2022.

從 22 年第一季度及以後，我們已決定修改我們對無形資產攤銷的調整後財務處理。此前，我們只排除了與大型併購相關的攤銷，並排除了所有無形資產的攤銷費用。預計這將為我們 2022 年調整後的稀釋後每股收益貢獻 0.06 美元，有助於提高與同行的可比性。 2022 年指引再次假設沒有股票回購。我們會注意到輝瑞公司在 2020 年或 2021 年都沒有回購股票。而且我們繼續——雖然我們仍然有未使用的授權來回購另外 53 億美元的股票，但考慮到潛在的增值業務發展機會，這可能是機會主義的，我們可以使用，我們預計不會在 2022 年回購股票。

Now a word on our 32% stake in the Consumer joint venture with GSK. As you know, GSK has announced its intention to engage in a demerger transaction for at least 80% of its 68% stake in the JV in the summer of 2022. We talked about our stake as a noncore asset, whose value we will seek to realize over time. While we have determined neither the manner or timing of how we will do so, there are a number of possible alternatives and we will attempt to monetize this asset in the manner which will create the most value for our shareholders.

現在談談我們與葛蘭素史克在消費者合資企業中 32% 的股份。如您所知，葛蘭素史克已宣布打算在 2022 年夏季對其持有的合資企業 68% 股權中的至少 80% 進行分拆交易。我們談到了我們作為非核心資產的股權，我們將尋求其價值隨著時間的推移意識到。雖然我們還沒有確定我們將如何做到這一點的方式或時間，但有許多可能的替代方案，我們將嘗試以能為我們的股東創造最大價值的方式將該資產貨幣化。

We receive approximately $600 million in pretax income from the JV annually, and this will not change as a result of the demerger transaction, and our guidance assumes that this will continue throughout 2022 with no change to our 32% stake.

我們每年從合資企業獲得約 6 億美元的稅前收入，這不會因分拆交易而改變，我們的指導假設這將持續到 2022 年，我們 32% 的股份不會發生變化。

Let me quickly remind you of some assumptions and context on the projected COVID-19 vaccine contribution and our collaboration agreement. The Pfizer-BioNTech COVID-19 vaccine collaboration construct is a 50-50 gross profit split. Pfizer books the vast majority of the global collaboration revenue, except for Germany and Turkey, where we receive a profit share from BioNTech, and we do not participate in the China region. We continue to expect that we can manufacture 4 billion doses in total by the end of 2022. And -- the $1 billion increase in expected COVID vaccine revenues to approximately $32 billion in 2022 primarily represents the impact of contracts signed since mid-December, which we cut off from our prior guidance. While we cannot predict what may be needed due to Omicron or other variants, I would also caution you that there is less potential upside to this guidance through the year compared to the situation we faced in 2021 when the vaccine was newly available and few people have received any doses of the vaccine.

讓我快速提醒您有關預計的 COVID-19 疫苗貢獻和我們的合作協議的一些假設和背景。輝瑞-BioNTech COVID-19 疫苗合作結構是 50-50 的毛利潤分成。除了德國和土耳其，我們從 BioNTech 獲得利潤分成，而且我們不參與中國地區，輝瑞公司記賬了全球合作收入的絕大部分。我們繼續預計，到 2022 年底，我們總共可以生產 40 億劑疫苗。而且——預計到 2022 年 COVID 疫苗收入將增加 10 億美元，達到約 320 億美元，這主要代表了自 12 月中旬以來簽訂的合同的影響，其中我們切斷了之前的指導。雖然我們無法預測由於 Omicron 或其他變體可能需要什麼，但我還要提醒您，與我們在 2021 年新推出疫苗且很少有人擁有疫苗時所面臨的情況相比，該指南全年的潛在上行空間較小接種過任何劑量的疫苗。

As you will remember, our cost of sales for the COVID-19 vaccine revenue includes manufacturing and distribution costs, applicable royalty expenses and payments of BioNTech representing 50% gross profit split. We expect that the Adjusted income before tax margin for the COVID-19 vaccine contribution to be slightly higher than the high 20s as a percentage of revenue that we had in 2021.

您會記得，我們的 COVID-19 疫苗收入的銷售成本包括製造和分銷成本、適用的特許權使用費和 BioNTech 的付款，佔毛利潤的 50%。我們預計 COVID-19 疫苗貢獻的調整後稅前收入占我們 2021 年收入的百分比將略高於 20 年代的高位。

Unlike the situation for Comirnaty, demand for Paxlovid should have upside from these levels depending on the outcomes of discussions with certain governments and potential purchases for stockpiling against future coronavirus pandemics. If we remove the projected COVID-19 vaccine and Paxlovid contribution from both periods, you will see that we expect the 2022 revenue range to be $45 billion to $47 billion, representing approximately 5% operational revenue growth at the midpoint.

與 Comirnaty 的情況不同，對 Paxlovid 的需求應該會從這些水平上升，這取決於與某些政府的討論結果以及為應對未來的冠狀病毒大流行而進行的潛在購買。如果我們從這兩個時期剔除預計的 COVID-19 疫苗和 Paxlovid 貢獻，您會看到我們預計 2022 年的收入範圍為 450 億美元至 470 億美元，在中點時運營收入增長約 5%。

Please remember, our guidance excludes the former revenue contribution of approximately $300 million for Meridian and all '21 quarters have been recast to exclude Meridian's discontinued operations accounting for its divestiture. Going forward, we will not give earnings guidance, excluding the estimated income from our Comirnaty direct sales and alliance revenues and Paxlovid. However, to help you with your forecasting a couple of minutes ago, I gave you my view on 2022 Comirnaty pretax margins. For Paxlovid, I would think about its margins as being typical for a small molecule drug and unlike Comirnaty, it is expected not to be dilutive to pretax earnings. To help you further, several years ago before COVID-19 existed, I spoke about our business being on a path to a 40%-plus pretax margin level in 2022, the business, excluding Comirnaty and Paxlovid. Going forward, we will continue to be prudent in our capital allocation activities with the opportunities for deployment shown here on this slide.

請記住，我們的指導不包括 Meridian 之前約 3 億美元的收入貢獻，並且所有 21 個季度都已重新調整，以排除 Meridian 因剝離而終止的業務。展望未來，我們將不提供收益指導，不包括來自我們的 Comirnaty 直接銷售和聯盟收入以及 Paxlovid 的估計收入。但是，為了幫助您在幾分鐘前進行預測，我向您介紹了我對 2022 年 Comirnaty 稅前利潤率的看法。對於 Paxlovid，我認為它的利潤率對於小分子藥物來說是典型的，並且與 Comirnaty 不同，預計它不會稀釋稅前收益。為了進一步幫助您，幾年前在 COVID-19 出現之前，我談到了我們的業務正在朝著 2022 年 40% 以上的稅前利潤率水平邁進，該業務不包括 Comirnaty 和 Paxlovid。展望未來，我們將繼續謹慎地進行資本分配活動，並在本幻燈片中顯示部署機會。

In summary, exceptionally strong quarter and year based on continued strong performance for our growth drivers. During the year, we raised guidance and for the year, we met or exceeded our guidance in all key metrics. Our pipeline continues to advance, and we have invested record amounts to support that advance. Last week, Arena shareholders voted to approve Pfizer's acquisition of the company. We look forward to a targeted closing of the Arena acquisition as soon as the first half of 2022, subject to the satisfaction of the closing conditions, including antitrust approvals. We continue to expect to be active in regards to business development throughout 2022 as we continue to get access to the best external science and bring breakthroughs to patients in 2025 and beyond. With that, let me turn it over to Chris to start the Q&A session.

總而言之，基於我們增長動力的持續強勁表現，季度和年度異常強勁。在這一年中，我們提出了指導，並且在這一年中，我們在所有關鍵指標上都達到或超過了我們的指導。我們的管道繼續推進，我們已投入創紀錄的金額來支持這一進展。上週，Arena 股東投票批准輝瑞收購該公司。我們期待盡快在 2022 年上半年有針對性地完成對 Arena 的收購，但前提是要滿足包括反壟斷批准在內的完成條件。隨著我們繼續獲得最好的外部科學並在 2025 年及以後為患者帶來突破，我們繼續期望在整個 2022 年積極參與業務發展。有了這個，讓我把它交給克里斯開始問答環節。

Thank you, Frank. Apologies, everyone, for those technical difficulties. Just want to remind you, we do have the prepared remarks posted to the website. So if there's anything you missed because of difficulties, please refer to the prepared remarks. And given the technical difficulties, we're going to try to let the Q&A session run a little longer to answer people's questions. Sylvia, first question, please?

謝謝你，弗蘭克。對於這些技術困難，大家深表歉意。只是想提醒您，我們確實已將準備好的備註發佈到網站上。所以如果你因為困難而遺漏了什麼，請參考準備好的備註。考慮到技術上的困難，我們將嘗試讓問答環節延長一點時間來回答人們的問題。西爾維婭，請問第一個問題？

Your first question comes from the line of Geoff Meacham from Bank of America Securities.

您的第一個問題來自美國銀行證券公司的 Geoff Meacham。

Just had to -- the first one, on Paxlovid guidance. I know you guys are factoring in only signed agreements. But could you give us a general sense as to agreements or doses perhaps that are under discussion? And is that dependent on the supply ramping? The second question, on external BD, Albert, I understand the strategy. I think the uncertainty is really the ability to scale some of the products that you brought in. So if COVID is less of a long-term contributor than you assume, what's the appetite to do higher-impact larger deals? You clearly have the capacity.

只需要 - 第一個，關於 Paxlovid 指導。我知道你們只考慮簽署的協議。但是，您能否就可能正在討論的協議或劑量給我們一個一般性的認識？這是否取決於供應的增加？第二個問題，關於外部BD，Albert，我理解策略。我認為不確定性實際上是擴展您引入的某些產品的能力。因此，如果 COVID 的長期貢獻者沒有您想像的那麼大，那麼進行影響更大的大型交易的意願是什麼？你顯然有這個能力。

Thank you. Angela, do you want to take a little bit the Paxlovid?

謝謝你。安吉拉，你想吃一點 Paxlovid 嗎？

Sure. So currently, we are in active discussions with over 100 countries and governments around the world. So I'd say that the discussions are going really well. In terms of where we are with the contracting, as you say, we've included some of the contracts that we already are -- that we have. But of course, this number changes every day and contracts are being secured and distribution agreements being secured literally on a day-to-day basis. So I think that this is a number to watch out for, and we do continue to expect movement.

當然。因此，目前，我們正在與全球 100 多個國家和政府進行積極討論。所以我想說，討論進展得非常順利。正如你所說，就我們在合同方面的情況而言，我們已經包括了一些我們已經存在的合同——我們已經擁有的合同。但是，當然，這個數字每天都在變化，並且每天都在保證合同和分銷協議的安全。所以我認為這是一個需要注意的數字，我們確實會繼續期待運動。

I think that there is a tremendous amount of interest for our product. And certainly, as the clinical program continues to develop and emerge. As you know, we only have the high-risk study right now. We still have the standard risk and the prophylaxis that's coming up. And I think that the full clinical program will also be another point of impetus for contracting and ordering. So I think it's going just really well and more to come on this one.

我認為我們的產品引起了極大的興趣。當然，隨著臨床項目的不斷發展和出現。如您所知，我們現在只有高風險研究。我們仍然有標準的風險和即將到來的預防措施。而且我認為完整的臨床計劃也將成為簽約和訂購的另一個推動點。所以我認為這件事進展得非常順利，而且還有更多。

Thank you. Aamir, maybe some comments on the BD.

謝謝你。 Aamir，也許是對 BD 的一些評論。

Sure. Thanks for the question, Geoff. I think in terms of the top line, we're going to be incredibly flexible. We have said repeatedly that we are most interested in compounds that have potential to be real breakthroughs. And this can take the form of later-stage clinical development as well as earlier-stage medical innovation. We're going to bias to the TAs, Oncology, I&I, Rare, Vaccines, Internal Medicine and Hospital where we've got the scientific chops to make good choices and add real value. And we're going to be flexible on the deal types. Acquisitions are obviously very much in the cards, but strategic partnerships and alliances are well. And in fact, some of our best successes have come from some capital-light collaborations. If we see a larger opportunity that's strategic and creates value and meets the criteria that I just described, we've obviously got the balance sheet to utilize to do that. So we certainly will look at those. But we're going to talk about and focus on the priorities that I described more so than synergy-driven deals per se.

當然。謝謝你的問題，傑夫。我認為就收入而言，我們將非常靈活。我們一再說過，我們最感興趣的是有潛力成為真正突破的化合物。這可以採取後期臨床開發和早期醫療創新的形式。我們將偏向於 TA、腫瘤學、I&I、Rare、疫苗、內科和醫院，在這些領域我們擁有科學印章，可以做出正確的選擇並增加真正的價值。我們將靈活處理交易類型。收購顯然非常有可能，但戰略夥伴關係和聯盟也很好。事實上，我們的一些最佳成功來自一些輕資本合作。如果我們看到一個更大的戰略機會，創造價值並符合我剛才描述的標準，我們顯然可以利用資產負債表來做到這一點。所以我們肯定會看看這些。但我們將討論並關注我所描述的優先事項，而不是協同驅動的交易本身。

Thank you, Aamir. And Geoff, just to add to both points because I'm sure that both will be asked a lot. On the Paxlovid, clearly, the numbers could become way bigger than what we have right now. But this is not something that we have done in the past, and we don't plan to do right now to give based on what could be the potential as a guidance. We are giving guidance based on what it is more or less secure, either signed deals or already agreed but not signed yet deal, but agreed price and volumes, I mean.

謝謝你，阿米爾。還有 Geoff，我想補充一下這兩點，因為我相信這兩個問題都會被問到很多。顯然，在 Paxlovid 上，這些數字可能會比我們現在擁有的要大得多。但這不是我們過去做過的事情，我們現在不打算根據可能作為指導的潛力去做。我的意思是，我們根據它或多或少的安全性提供指導，無論是已簽署的交易還是已經商定但尚未簽署的交易，但商定的價格和數量。

So clearly, if you remember, when we started with the vaccine, we -- in the beginning, we had a guidance of, I think, $15 billion in the first quarter, something like that. Eventually, it made $36 billion. Here, we start even stronger on our first production with Paxlovid. So -- and that's why we manufacture and we move ahead with our plans and already, we are at 120 million treatments, and we have the ability to go higher if the discussions that we are having materialize at all.

很清楚，如果你還記得，當我們開始使用疫苗時，我們 - 一開始，我認為第一季度的指導是 150 億美元，類似的東西。最終，它賺了 360 億美元。在這裡，我們開始使用 Paxlovid 製作我們的第一部作品。所以 - 這就是我們製造並推進我們的計劃的原因，我們已經有 1.2 億次治療，如果我們正在進行的討論完全實現，我們有能力走得更高。

In terms of also the business development, I just want to emphasize that because I'm getting a lot of this question on the size. We are agnostic to size. Where we are biased, it is deals. But in order to justify the premium, we will have to do significant cost synergies. This is not -- these are -- could be very profitable deals for other, let's say, periods of the history of the company, not now.

就業務發展而言，我只想強調這一點，因為我收到了很多關於規模的問題。我們不知道大小。我們有偏見的地方就是交易。但為了證明溢價的合理性，我們將不得不進行顯著的成本協同效應。這不是——這些是——對於公司歷史上的其他時期來說可能是非常有利可圖的交易，而不是現在。

Right now, the company is having a manufacturing machine, but it is performing at its best; an R&D machine, but it's performing at its best; a commercial machine that keeps being the leader in the industry in terms of the ability to execute and deliver. So the last thing I want to do, it is to do a deal that in order to justify the premium to the shareholders of the other company, we will have to shut down manufacturing sites and to consolidate research sites and consolidate field forces so that we can justify -- so we can generate the cost synergies.

目前，該公司擁有一台製造機器，但它的性能處於最佳狀態；一台研發機器，但它的性能處於最佳狀態；在執行和交付能力方面一直處於行業領先地位的商用機器。所以我最不想做的事情是做一筆交易，為了向另一家公司的股東證明溢價的合理性，我們將不得不關閉生產基地，整合研究基地和整合現場力量，以便我們可以證明——所以我們可以產生成本協同效應。

This is not the time to disrupt the momentum of the company. This is the time to bring into this manufacturing machine, the research machine, the commercial machine more substrate in addition to what we produce organically ourselves. And this is why the business development is aiming in these areas. So let's go to the next one.

現在不是破壞公司發展勢頭的時候。除了我們自己有機生產的產品外，現在是時候將更多的基板帶入這台製造機器、研究機器、商用機器。這就是為什麼業務發展瞄準這些領域的原因。那麼讓我們進入下一個。

Your next question comes from Mohit Bansal from Wells Fargo.

您的下一個問題來自富國銀行的 Mohit Bansal。

Maybe one on Paxlovid. So there have been some news reports talking about logistical and access issues for Paxlovid. And I understand that supply is tight for now. But would love to get your thoughts on how you're working on improving the logistics when the supply is no longer an issue, especially in a world where home testing will become a norm and one needs to take this drug within 5 days of diagnostics.

也許是 Paxlovid 上的一個。因此，有一些新聞報導談到了 Paxlovid 的後勤和訪問問題。我知道目前供應緊張。但是，如果供應不再是問題，特別是在家庭測試將成為常態並且需要在診斷後 5 天內服用這種藥物的世界，您希望了解您如何改善物流。

I wouldn't say that we have logistical issues of supply. But Angela, would you like to take that, please?

我不會說我們有供應的後勤問題。但是安吉拉，你願意接受嗎？

Sure. So first of all, again, our deliveries and our allocations for the doses have gone extremely well here in the U.S. Just to give you some context, 265,000 doses have been allocated by the U.S. government since the EUA was approved. And of that 265,000, 85% of all the doses have been ordered. So -- and we see a range of ordering patterns from the states. Some states are ordering 100% of the allocation. Others are at 80%, 70%, so on and so forth. So there's really only a handful that haven't really ordered up to their allocation. But I would say, for the most part, the weekly orders are going up and increasing week by week, and there is a very strong placement of orders. So I'd say that the drawdown, right, of the doses and the utilization is going really well. And again, it's different by state what the allocations are and how that's going.

當然。因此，首先，再一次，我們在美國的交付和劑量分配都非常順利。為了給你一些背景信息，自 EUA 獲得批准以來，美國政府已經分配了 265,000 劑。在這 265,000 劑中，已訂購了所有劑量的 85%。所以——我們看到了來自各州的一系列排序模式。一些州正在訂購 100% 的分配。其他的則為 80%、70%，依此類推。因此，實際上只有少數沒有真正訂購到他們的分配。但我想說的是，在大多數情況下，每週的訂單都在增加，並且每週都在增加，並且下單非常強勁。所以我想說的是，劑量和利用率的下降，對的，進展順利。再說一次，分配是什麼以及如何進行的狀態會有所不同。

And then as Albert said, I don't know that we have logistical -- there are not logistical issues. I think initially, what was difficult was that it was not clear where the doses were being located because every state had a different system for where to actually distribute Paxlovid from. But there are a number of tools now that have gone up online, both at the state level as well as on Pfizer's website.

然後正如阿爾伯特所說，我不知道我們有後勤問題——不存在後勤問題。我認為最初的困難在於不清楚劑量的位置，因為每個州都有不同的系統來實際分配 Paxlovid。但是現在有許多工具已經上線，無論是在州一級還是在輝瑞的網站上。

We've taken the state government tool and also loaded it on our website so that both HCPs and patients can see where Paxlovid is being -- where it's available and where the orders as well as prescriptions can be placed. So I think in that regard, that's all been ironed out. I think looking forward into the future, I mean, clearly, having a seamless sort of end-to-end from diagnosis, positive results to them being able to prescribe quickly and having the patient be able to acquire the drug quickly, is our goal. And I think on all of those fronts, we're working with a number of partners, both from a testing and a diagnostics perspective, but also from a telemedicine perspective and from a pharmacy perspective to ensure that we have as fast and as efficient, I can say, a patient journey, right, from diagnosis right onto treatment. So all of that is in place, and you'll hear more -- you'll continue to hear more about that as the launch and as the utilization increases.

我們採用了州政府工具並將其加載到我們的網站上，以便 HCP 和患者都可以看到 Paxlovid 的位置——它在哪裡可用以及可以在哪裡下訂單和處方。所以我認為在這方面，這一切都已經解決了。我認為展望未來，我的意思是，很明顯，從診斷、積極的結果到他們能夠快速開出處方並讓患者能夠快速獲得藥物，這是我們的目標.我認為在所有這些方面，我們正在與許多合作夥伴合作，無論是從測試和診斷的角度，還是從遠程醫療的角度和藥房的角度，以確保我們擁有盡可能快和高效，我可以說，從診斷到治療，是一段耐心的旅程。所以所有這些都已經到位，你會聽到更多——隨著發布和利用率的增加，你會繼續聽到更多關於它的信息。

So again, to punctuate and give a little bit of context to what Angela said. The 85% that -- it has already been ordered from the quantities that we are making available to the U.S. government, it's a very, very high number. For example, the same number in the first month for vaccines, if you remember well, if you remember from that time, was dramatically lower than that because it takes time for the states to get their act together. And it is really variable state by state.

再次強調一下，並為安吉拉所說的內容提供一點背景。 85% 已經從我們提供給美國政府的數量中訂購，這是一個非常非常高的數字。例如，第一個月的疫苗數量相同，如果你記得清楚的話，如果你記得從那時起，就會大大低於這個數字，因為各州需要時間來共同採取行動。它實際上是逐州可變的。

So there are states right now that once the quantities are made to them available, they are ordering immediately. And there are states that take their time until they get their act together for the distribution. In general, way, way, way more efficient than what used to be in the first month of the vaccine. Also, what is extremely important it is that every week, there is constant replenishment, which although we do not have right now data for scripts because it's too early, what we do have, it is that the quantities that the states are accumulating, they're disappearing and then immediately, they are placing orders.

因此，現在有些州一旦向他們提供數量，他們就會立即訂購。有些州會花時間直到他們為分發而採取行動。總的來說，比接種疫苗第一個月的效率要高得多。另外，非常重要的是每週都有不斷的補充，雖然我們現在還沒有腳本數據，因為太早了，但我們有的是，各州正在積累的數量，他們'正在消失，然後他們立即下訂單。

So I would say we have, let's say, we are pretty happy with the way that the first month, the collaboration with the U.S. government went in terms of allocating doses. And there is dramatically also improvement in the tools as Angela described. But the bigger improvement will come from the fact that the second month, we'll make available way more quantities. In the third month, way more quantities because the issues right now for people trying to find it, it is that it is in a few places in the state because you can't expand the network of places that it is available when you have smaller quantities. So that will be very, very different in this month. And basically, all over the place, I think, in the third month where significant quantities will be delivered. Okay. I think let's go to the next question.

所以我想說，我們對第一個月與美國政府在分配劑量方面的合作方式感到非常滿意。正如安吉拉所描述的那樣，工具也有了顯著的改進。但更大的改進將來自於第二個月，我們將提供更多數量的產品。在第三個月，數量要多得多，因為現在對於試圖找到它的人來說是個問題，它在該州的一些地方，因為你無法擴展它的可用地方網絡，當你有更小的時候數量。所以這個月會非常非常不同。基本上，我認為，在第三個月將交付大量貨物。好的。我想讓我們進入下一個問題。

Next question is from Evan Seigerman from BMO Capital Markets.

下一個問題來自 BMO Capital Markets 的 Evan Seigerman。

I was wondering if you could provide an update on the SEC review process for the Arena deal. If I'm not mistaken, there was a recent procedural move where you and Arena were through the -- where you refiled the HSR Act filing essentially to allow the FTC an additional 30 days for review. And then I'd also love for you to walk me through your assumptions on how you forecast $13 billion in revenue from BD transactions. That would imply that your specific targets and combination of targets in mind. Any color here that you could provide would be very helpful.

我想知道您是否可以提供有關 Arena 交易的 SEC 審查流程的最新信息。如果我沒記錯的話，你和 Arena 最近有一個程序性舉措——你重新提交了 HSR 法案文件，基本上是為了讓 FTC 再有 30 天的時間進行審查。然後我也希望你能告訴我你如何預測 130 億美元的 BD 交易收入的假設。這意味著您的特定目標和目標組合牢記在心。您可以提供的任何顏色都會非常有幫助。

Yes. Thank you very much. On the last one, just to make sure, but this is not our assumption. Our assumption is way higher of the $13 billion. What I just gave you, it is what is the consensus of the deals that we have signed so far. But on the FTC review, I would like to ask Doug to provide us maybe a review on that, Doug Lankler, our General Counsel.

是的。非常感謝你。最後一個，只是為了確定，但這不是我們的假設。我們的假設遠高於 130 億美元。我剛才給你的，是我們迄今為止簽署的協議的共識。但是關於 FTC 的審查，我想請 Doug 向我們提供一個審查，我們的總法律顧問 Doug Lankler。

Yes. As you pointed out, we did request to refile, which is not unusual. Under -- it's -- the deal is, of course, subject to customary closing conditions and typical antitrust clearance and shareholder approval, which, as you know, we've received. We don't expect a significant break in time from our proposed sense that the deal will close in the first half of this year. We still expect it to close in the first half of this year.

是的。正如你所指出的，我們確實要求重新提交，這並不罕見。根據 - 它是 - 這筆交易當然取決於慣例成交條件和典型的反壟斷許可和股東批准，如你所知，我們已經收到了。我們預計交易將在今年上半年完成的提議不會有重大突破。我們仍然預計它會在今年上半年關閉。

Thank you. And Aamir, although I did explain that this is consensus numbers, not our numbers. Do you want to make any other comment on the $13 billion of 2030 revenues? That consensus for cash for the deals that we have signed?

謝謝你。還有 Aamir，雖然我確實解釋過這是共識數字，而不是我們的數字。您想對 2030 年 130 億美元的收入發表任何其他評論嗎？我們已經簽署的交易的現金共識？

Yes. The only thing I would add is we feel very good about the progression of all of the substrate and the deals since 2019 that Albert outlined. We've seen a significant number of approvals and EUAs in that group, submissions as well as quite a few Phase 3 starts. So we think that, that substrate is progressing well. And the $13 billion is the consensus number. Our expectations of what's there are materially higher. And there are a number of transactions. We spoke to Trillium, Biohaven and even some of the recent things that we've done in mRNA that are not yet factored in the consensus forecast on those transactions.

是的。我唯一要補充的是，我們對 Albert 概述的自 2019 年以來所有基板和交易的進展感覺非常好。我們已經看到該組中的大量批准和 EUA、提交以及相當多的第 3 階段啟動。所以我們認為，基板進展順利。 130 億美元是共識數字。我們對實際情況的期望更高。並且有許多交易。我們採訪了 Trillium、Biohaven，甚至我們最近在 mRNA 上所做的一些事情，這些事情尚未納入對這些交易的共識預測中。

Your next question comes from Umer Raffat from Evercore ISI.

您的下一個問題來自 Evercore ISI 的 Umer Raffat。

Perhaps 2 on vaccines today, if I may. First, on the flu vaccine, I know you've had a trial ongoing on your modRNA since September. And I noticed you just initiated a new trial of a self-amplifying mRNA for flu. And I wonder if the decision to progress a second mRNA program in flu was triggered by any emerging data from your first-gen flu Phase 1 that's been ongoing? And then secondly, on Omicron-specific booster, perhaps in light of some of the emerging data on immunogenicity differences or lack thereof versus regular COVID vaccine, I guess my question is, what's your confidence on ability to show superiority of an Omicron-specific booster versus regular? And what would be the regulatory criteria?

如果可以的話，今天可能有 2 個關於疫苗的問題。首先，關於流感疫苗，我知道您自 9 月以來一直在對您的 modRNA 進行試驗。我注意到你剛剛啟動了一項針對流感的自我擴增 mRNA 的新試驗。我想知道在流感中進行第二個 mRNA 程序的決定是否是由您正在進行的第一代流感第一階段的任何新數據觸發的？其次，關於 Omicron 特異性助推器，也許鑑於與常規 COVID 疫苗相比免疫原性差異或缺乏免疫原性差異的一些新興數據，我想我的問題是，您對展示 Omicron 特異性助推器優勢的能力有什麼信心與常規相比？監管標準是什麼？

I think Mikael can take that question. On the flu vaccine, just to make sure that I clarify, the plan was always to initiate an samRNA for flu and to run the 2 programs in parallel. It's not that we saw data that forced us to do an SA. It was always the plan. We are advancing new forms of mRNA technology in SA. It is one of the most promising next generation of RNA technologies. But Mikael, any comments on that and on the Omicron-specific, our confidence for superiority?

我認為 Mikael 可以回答這個問題。關於流感疫苗，只是為了確保我澄清，計劃總是為流感啟動 samRNA 並並行運行 2 個程序。並不是我們看到了迫使我們進行 SA 的數據。這一直是計劃。我們正在南非推進新形式的 mRNA 技術。它是最有前途的下一代 RNA 技術之一。但是 Mikael，對此以及 Omicron 特定的，我們對優勢的信心有何評論？

Thank you. Yes, we are accumulating, first of all, from our mod mRNA data trial data on various regimens and on multivalent constructs. We remain of the view that we aspire to develop a flu vaccine. Currently, the most aggressive timelines are focused on the mod mRNA. Our plans is to develop something that have differentiation versus the current heptavalent standard of care. I know other companies have spoken about being similar, while at this moment, we still see opportunities to possibly differentiate with an mRNA based on mod mRNA.

謝謝你。是的，首先，我們正在從我們的 mod mRNA 數據試驗數據中積累關於各種方案和多價構建體的數據。我們仍然認為我們渴望開發流感疫苗。目前，最激進的時間線集中在 mod mRNA 上。我們的計劃是開發與當前七價護理標準不同的產品。我知道其他公司也談到了類似的情況，而目前，我們仍然看到了可能與基於 mod mRNA 的 mRNA 進行區分的機會。

As Albert alluded to, we are actually filing the IND for the self-amplified. I think the protocol may have gone up already on ClinicalTrials.gov, but dosing is going to be within the next couple of months or so. And it's entirely based on us aiming to develop that platform, which has particular relevance for combination vaccine given that possibly, we expect to have much lower mRNA burden and can, over time, build vaccine combination of several different pathogens. We'll keep you updated on progress with the mod mRNA in flu. And we certainly see data that suggests that this is a feasible path, and we are working to refine our approach to aim for a differentiated vaccine.

正如 Albert 所暗示的，我們實際上是在為自我放大提交 IND。我認為該方案可能已經在 ClinicalTrials.gov 上發布，但劑量將在未來幾個月左右進行。它完全基於我們旨在開發該平台的目標，該平台與組合疫苗特別相關，因為我們可能期望具有更低的 mRNA 負擔，並且可以隨著時間的推移構建幾種不同病原體的疫苗組合。我們將讓您了解流感中 mod mRNA 的最新進展。我們當然看到數據表明這是一條可行的道路，我們正在努力改進我們的方法，以研製出差異化的疫苗。

What about Omicron? How confident we are about the superiority?

歐米光呢？我們對優勢有多大信心？

Yes. The regulatory path is that we expect to have -- if successful, an Omicron boost would show higher neutralizing antibodies for Omicron versus a similar boost by the wild type vaccine and acceptable titers to the other previously available strains to provide -- preserve broad protection, but possibly with higher Omicron.

是的。監管路徑是，我們期望 - 如果成功，Omicron 加強將顯示更高的 Omicron 中和抗體，而野生型疫苗的類似加強和其他先前可用菌株的可接受滴度 - 保持廣泛的保護，但可能使用更高的 Omicron。

I really think we should let the science play out here. We are talking about a number of weeks before we get data. And as I alluded to, it has 3 different arms on top of 3 doses, Omicron versus a wild type. That was on top of 3 previous doses on top of 2 previous vaccine doses, 1 or 2 Omicron. That will be a very interesting data set and then Omicron or naive. So I think it's a really interesting trial and we'll extract a lot of data and we'll report whether we can get that superiority.

我真的認為我們應該讓科學在這裡發揮作用。我們談論的是在獲得數據之前的幾週。正如我所提到的，它在 3 個劑量之上有 3 個不同的臂，Omicron 與野生型。這是在之前的 2 劑疫苗（1 或 2 Omicron）之上的 3 劑。那將是一個非常有趣的數據集，然後是 Omicron 或 naive。所以我認為這是一個非常有趣的試驗，我們會提取大量數據，我們會報告我們是否可以獲得這種優勢。

But in any case, I would just want to punctuate that our current vaccine is active of the 3 doses and raise relevant neutralizing antibodies. And the T cell responses that we see are likely the one that contribute in real-world evidence to provide effective protection of the current vaccine against hospitalization and death. Omicron vaccine is an interesting opportunity that we learn more about. But our science is progressing against several dimensions on how to further improve over time mRNA vaccines, although they're all pretty good ones. So you should expect Pfizer continue to be a leader in this field through multiple approaches together with BioNTech.

但無論如何，我只想強調一下，我們目前的疫苗在 3 劑疫苗中是有活性的，並會產生相關的中和抗體。我們看到的 T 細胞反應很可能有助於提供真實世界的證據，以有效保護當前疫苗免於住院和死亡。 Omicron 疫苗是我們了解更多的有趣機會。但是我們的科學在如何隨著時間的推移進一步改進 mRNA 疫苗的幾個方面取得了進展，儘管它們都是非常好的疫苗。因此，您應該期望輝瑞與 BioNTech 一起通過多種方法繼續成為該領域的領導者。

Your next question comes from Louise Chen from Cantor.

您的下一個問題來自 Cantor 的 Louise Chen。

So my first question for you is, what are the key pushes and pulls to your underlying business, excluding COVID? And what gives you confidence that you can still meet that top line sales guidance that you gave through 2025 despite some of the volatility that we're seeing right now? And then I just wanted to ask you on your TL1A antibody and where you are with development of that product and the reporting of data. Have you changed any of the timelines for when you report data?

所以我問您的第一個問題是，除了 COVID 之外，您的基礎業務的關鍵推動力和拉力是什麼？儘管我們現在看到了一些波動，但什麼讓您有信心仍然可以滿足您在 2025 年之前給出的頂級銷售指導？然後我只是想問你關於你的 TL1A 抗體的問題，以及你在開發那個產品和報告數據方面的進展。您是否更改了報告數據的任何時間表？

On the 6%, what gives us confidence, it is that we are -- we keep meeting the goal, as I said, that we set the goal in '19 for a 6% all the way CAGR. And then we had -- year-to-date, we are at 6% right now. The year, particularly, it is at 5% for the underlying business. But there is a little bit of volatility. But always, we knew that this will be a year that we are losing some of the revenues of Chantix and compared to previous year, which affects quite significant this deal, which then as we are launching new products that are coming up. Maybe I will ask Angela to give a little bit more details on the inputs and how this is progressing and also, Mikael, on the antibody question. Angela?

在 6% 上，讓我們充滿信心的是，我們一直在實現目標，正如我所說，我們在 19 年設定的目標是 6% 的複合年增長率。然後我們有 - 年初至今，我們現在是 6%。尤其是這一年，基礎業務為 5%。但有一點波動。但我們一直都知道，與前一年相比，今年我們將失去一些 Chantix 的收入，這對這筆交易產生了相當大的影響，因為我們正在推出即將推出的新產品。也許我會請安吉拉提供更多關於輸入的詳細信息，以及這是如何進展的，還有米凱爾，關於抗體問題。安吉拉？

Thank you, Louise. I think the 6% confidence is really driven by 2 things. First of all, the launches, right, that will take place between now and 2025, which will continue to drive growth for us. But also importantly, in our in-line portfolio, Louise, every single one of our products still have opportunities to grow. They can grow from a number of different ways, right? There's still under-diagnosed patients. So from new diagnosis, we can continue to drive a tremendous amount of growth in Eliquis and in Vyndaqel. In many of our products, we still have class growth.

謝謝你，路易絲。我認為 6% 的信心實際上是由兩件事驅動的。首先，從現在到 2025 年的發布會，對我們來說，這將繼續推動我們的增長。但同樣重要的是，在我們的在線產品組合 Louise 中，我們的每一款產品仍然有增長的機會。他們可以通過多種不同的方式成長，對吧？仍有未確診的患者。因此，從新的診斷開始，我們可以繼續推動 Eliquis 和 Vyndaqel 的巨大增長。在我們的許多產品中，我們仍然有階級增長。

I mean think about the CDK4/6s, think about XTANDI, think about BRAF/MEKTOVI. These are all therapies that are still, I think, underutilized from a class perspective. So there's growth there. And then finally, for all of them, there's the opportunity to grow in terms of market share, just given just the strong clinical profile and strong life cycle support that we have for all of our products. So I think we see tremendous amount of growth still. We just have not tapped out of growth in our core in-line brands. And then you add on top of that the launch brands, this is where we're going to get our growth from.

我的意思是想想 CDK4/6s，想想 XTANDI，想想 BRAF/MEKTOVI。我認為，從階級的角度來看，這些都是仍未得到充分利用的療法。所以那裡有增長。最後，對於他們所有人來說，只要考慮到我們所有產品的強大臨床概況和強大的生命週期支持，就有機會在市場份額方面增長。所以我認為我們仍然看到了巨大的增長。我們只是沒有利用我們核心在線品牌的增長。然後你再加上發布品牌，這就是我們要從中獲得增長的地方。

Mikael?

邁凱爾？

Thank you, Angela. On the TL1A, as you remember at the previous earnings call, we showed some really strong data in the range of 34% endoscopic improvement and with a biomarker of 48% in the patients, way above expected standard of care. That trial has enrolled very fast. It's fully enrolled. Full trial readout will be Q4. We are obviously considering, based on the encouraging data in the previous trial, opportunity for interim analysis that pending data could allow us to accelerate development of the program towards potential pivotal studies. So all in, it's moving very well and very fast.

謝謝你，安吉拉。在 TL1A 上，正如您在上一次財報電話會議上所記得的那樣，我們展示了一些非常強勁的數據，內窺鏡改善了 34%，患者的生物標誌物為 48%，遠高於預期的護理標準。該試驗的註冊速度非常快。它已完全註冊。完整的試用版將在第四季度發布。基於先前試驗中令人鼓舞的數據，我們顯然正在考慮進行中期分析的機會，即未決數據可以使我們加速該計劃的發展，以實現潛在的關鍵研究。總之，它進展得非常好而且非常快。

Next question comes from Steve Scala from Cowen.

下一個問題來自 Cowen 的 Steve Scala。

Just to be absolutely clear, I understand that Pfizer wants to be conservative on Paxlovid. But it seems that Pfizer has merely scratched the surface on its 2022 potential and that scratching of the surface is what's in 2022 Paxlovid guidance. So please just tell me if you disagree with that statement.

絕對清楚，我知道輝瑞希望對 Paxlovid 持保守態度。但輝瑞似乎只是觸及了其 2022 年潛力的表面，而觸及表面正是 2022 年 Paxlovid 指南中的內容。因此，如果您不同意該聲明，請告訴我。

Secondly, and just to be clear, once again, do you not see growth for Pfizer overall in '25 to '30 without business development? And then lastly, on danuglipron, Slide 39 shows some very good data. I'm curious what was the discontinuation rate in the study? Can the dose be increased further? And does Pfizer expect additional weight loss beyond 12 weeks?

其次，再次澄清一下，如果沒有業務發展，您是否看不到輝瑞在 25 至 30 年的整體增長？最後，關於 danuglipron，幻燈片 39 顯示了一些非常好的數據。我很好奇這項研究的中止率是多少？可以進一步增加劑量嗎？輝瑞公司是否預計 12 週後會進一步減輕體重？

Yes. So let me take the 2 first questions, and then Mikael can take the research one. Look, it's not that we are giving a conservative guidance. What we do, we have principles that we follow because otherwise, we can be lost. And the principle that we are following, it is that we are only giving guidance for contracts that have been signed or they are very close to be signed because we have agreed critical terms, predominantly, right? So this is what you have heard about Paxlovid.

是的。所以讓我回答前兩個問題，然後 Mikael 可以回答研究問題。看，我們並不是在給出保守的指導。我們所做的，我們有我們遵循的原則，否則，我們可能會迷失。我們遵循的原則是，我們只對已經簽署或即將簽署的合同提供指導，因為我們主要就關鍵條款達成了一致，對吧？這就是您聽說過的有關 Paxlovid 的信息。

Clearly, this is only a very small fraction of the 120 million treatments that we are right now preparing to manufacture. And it is a small fraction of things that we are discussing right now around with different governments. But we are not taking, for example, an approach that we take all the discussions that we are having with the different governments, we risk adjust them to see how many things can go part through and then we give a guidance. This is not what we do. We only give -- and this is the same with the vaccines, things that have been signed or are already agreed by the time in a specific deadline. And I think that Frank said it was last week, I think, this deadline. So clearly, there is a lot of potential, but it is not that we are putting a little bit of our own conservatism in the numbers. We are following a principle so that we can always be clear with what we say and why we say it. So that's the thing then. What about the study dose and the 12 weeks delay, Mikael?

顯然，這只是我們目前準備生產的 1.2 億種治療方法中的一小部分。這只是我們現在正在與不同政府討論的事情的一小部分。但是，例如，我們沒有採取與不同政府進行所有討論的方法，我們冒著調整它們的風險，看看有多少事情可以參與，然後我們給出指導。這不是我們要做的。我們只給予——疫苗也是如此，在特定期限內已經簽署或已經同意的東西。我認為弗蘭克說這是上週，我想，這個截止日期。很明顯，有很多潛力，但這並不是說我們在數字中加入了一點我們自己的保守主義。我們遵循一個原則，以便我們始終清楚我們所說的內容和原因。事情就是這樣。研究劑量和 12 週的延遲怎麼樣，Mikael？

On the danuglipron, I'm pleased that you were happy and impressed with our data. And indeed, I would say the glucose lowering through HbA1c and the body weight that you know are probably among the best in such a short treatment period. Tolerability and discontinuation rates improved versus previous study because we extended the dose titration from week to 2 weeks. And overall safety adverse event, I think, are very much in line with what you see comparable titration approaches with injectable. Given that we see that we can improve tolerability and the discontinuations with this medium titration rate, we have -- the next studies coming up will be a further slow dose titration maybe up to a month or so. And we think that may even bring readouts of efficacy further above this, so we are very pleased with the profile. And I think the next study will nail down for us dose regimen and will help us to move with a strong profile into a potential pivotal study.

關於 danuglipron，我很高興您對我們的數據感到高興和印象深刻。事實上，我會說通過 HbA1c 降低的葡萄糖和你所知道的體重可能在如此短的治療期內是最好的。與之前的研究相比，耐受性和停藥率有所提高，因為我們將劑量滴定從一周延長至 2 週。我認為，總體安全性不良事件與您看到的可注射滴定方法非常一致。鑑於我們看到我們可以通過這種中等滴定率提高耐受性和停藥，我們有——接下來的研究將是進一步緩慢的劑量滴定，可能長達一個月左右。而且我們認為這甚至可能使功效讀數進一步超出此範圍，因此我們對配置文件非常滿意。而且我認為下一項研究將為我們確定劑量方案，並將幫助我們以強大的形象進入一項潛在的關鍵研究。

Your next question comes from Tim Anderson from Wolfe Research.

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

A few questions. The RSV vaccine data previously said early '22. Now you're saying first half '22. Does that imply there's been some slippage because early to me, I always felt that mid-January, February, something like that.

幾個問題。 RSV 疫苗數據此前表示 22 年初。現在你說的是 22 年上半年。這是否意味著出現了一些滑點，因為對我來說，早在 1 月中旬，2 月，我就一直感覺到類似的情況。

mRNA flu, second question. What's a realistic time frame for a potential regulatory filing of a product like that, assuming you find success in your trials? And then last question, the IBRANCE sales, soft. You say it's due to patient assistance programs. We haven't seen that impact on other CDK4/6s. And I haven't generally heard about those programs impacting other brands, either at Pfizer or other companies. So I'm wondering what else may be putting pressure on IBRANCE where you're having to cut price to maintain access.

mRNA流感，第二個問題。假設您在試驗中取得成功，對此類產品進行潛在監管備案的現實時間框架是多少？然後是最後一個問題，IBRANCE 的銷售，軟。你說這是由於患者援助計劃。我們還沒有看到對其他 CDK4/6 的影響。而且我通常沒有聽說過這些計劃會影響輝瑞或其他公司的其他品牌。所以我想知道還有什麼可能會給 IBRANCE 帶來壓力，因為您必須降價以維持訪問權限。

Yes. What was your question on flu, Tim?

是的。你對流感有什麼問題，蒂姆？

A realistic time frame for filing for approval of a mRNA flu vaccine.

申請批准 mRNA 流感疫苗的現實時間框架。

Yes. So why don't we go, Mikael? What about RSV? You can speak about both. We have both now, adult and maternal, and then the mRNA. And then Angela, you speak about IBRANCE.

是的。那麼我們為什麼不去，米凱爾？呼吸道合胞病毒呢？你可以談論兩者。我們現在有成人和母體，然後是 mRNA。然後安吉拉，你談到了 IBRANCE。

Yes. On the RSV, we have enrolled very well maternal and adult and are basically, I would say, fully enrolled. So it's entirely to ensure we have the number of events that we were looking for. And we expect both trials to read out, whether it's somewhere between Q1, Q2 or at the later part of Q2. We'll just see and as events accumulate, but it's going very well. So I feel very optimistic with RSV starting to conclude, and we're looking forward to that data.

是的。在 RSV 上，我們已經很好地註冊了孕產婦和成人，並且基本上，我想說，完全註冊。所以這完全是為了確保我們擁有我們正在尋找的事件數量。我們希望這兩項試驗都能讀出，無論是在第一季度、第二季度之間還是在第二季度後期。我們只會看到，隨著事件的累積，但進展非常順利。所以我對 RSV 開始得出結論感到非常樂觀，我們期待著這些數據。

mRNA flu, we are right now accumulating immunogenicity from several different type of dose regimens. And if we are able to conclude with the optimal dose regimen using the mod mRNA, a potential Phase 2, Phase 3 study could certainly be initiated this year. But of course, it's a little bit early to speculate before you have identified the right Phase 2/3 dose regimen. If we would embark on such a study this year, we expect it can conclude very fast given our experience to run very large trials in this sector and this population of adults. And so we're talking about possible conclusion then within next year. But it's -- I would say, one step at a time, we'll keep you informed. We are encouraged so far, and we'll go from there.

mRNA流感，我們現在正在從幾種不同類型的劑量方案中積累免疫原性。如果我們能夠得出使用 mod mRNA 的最佳劑量方案，那麼今年肯定會啟動一項潛在的 2 期、3 期研究。但是，當然，在您確定正確的 2/3 期劑量方案之前進行推測還為時過早。如果我們今年開始這樣的研究，我們預計它可以很快結束，因為我們有在這個領域和這個成年人群體中進行非常大的試驗的經驗。因此，我們正在討論明年內可能得出的結論。但這是 - 我會說，一次一步，我們會隨時通知您。到目前為止，我們受到鼓勵，我們將從那裡開始。

Thank you, Mikael. And then what about Angela on the IBRANCE?

謝謝你，米凱爾。那麼 IBRANCE 上的安吉拉呢？

Sure. I can confirm that the patient assistance program is indeed the primary reason for the decline in volume that you've seen on IBRANCE. Just to give you some perspective, in Q4 of 2021, our PAP prescriptions were up 32% compared to where it was in Q4 of 2020. And all of this is 53% more than what it was pre-COVID. And so this is really what has caused us a tremendous amount of paid prescriptions. And I can -- and that's really the primary reason. We also saw and throughout the year, and this has been something that we've been watching quarter-over-quarter, just some slowdown in new patient starts. And -- but we've seen this sort of phenomenon across multiple products in our portfolio. So there's a small contribution from that, but the largest contribution by far is truly this phenomenon we're seeing here in terms of PAP.

當然。我可以確認，患者援助計劃確實是您在 IBRANCE 上看到的數量下降的主要原因。只是為了給您一些視角，在 2021 年第四季度，我們的 PAP 處方與 2020 年第四季度相比增加了 32%。所有這些都比 COVID 之前增加了 53%。所以這確實是導致我們大量付費處方的原因。我可以——這確實是主要原因。我們還看到了全年，這是我們一直在觀察的季度環比情況，只是新患者開始的速度有所放緩。而且 - 但我們已經在我們的產品組合中的多個產品中看到了這種現象。所以這有一點貢獻，但迄今為止最大的貢獻確實是我們在 PAP 方面看到的這種現象。

Thank you, Angela. Before we move to the next question, I realized that I didn't answer one of the questions that Steve made, Steve Scala, about if we believe that we need business development to grow in the period, '25 to '30. And clearly, this is not the belief right now. We think that we have a clear LOE number that we estimate around $17 billion. And we have a pipeline that delivers more than the LOEs. So only organically, we would like to have right now in our calculations, we are a positive growth trajectory. The $25 billion I just mentioned needs to be on top of everything, the balance between LOEs and internal pipeline does, everything new that will be invented in the meantime and, of course, the COVID trajectory through 2030. But we don't need right now business development at all to grow. What we need business development is to maintain high level of 6% growth top line all the way to 2030, for example.

謝謝你，安吉拉。在我們轉到下一個問題之前，我意識到我沒有回答史蒂夫提出的史蒂夫斯卡拉的一個問題，即我們是否認為我們需要在 25 到 30 年期間實現業務發展。顯然，這不是現在的信念。我們認為我們有一個明確的 LOE 數字，我們估計約為 170 億美元。而且我們有一個管道，它提供的不僅僅是 LOE。所以只有有機地，我們現在希望在我們的計算中，我們是一個積極的增長軌跡。我剛剛提到的 250 億美元需要在一切之上，LOE 和內部管道之間的平衡，同時將發明的所有新事物，當然還有到 2030 年的 COVID 軌跡。但我們不需要正確現在業務發展完全可以增長。例如，我們需要的業務發展是保持 6% 的高增長收入水平一直到 2030 年。

Your next question comes from Andrew Baum from Citi.

您的下一個問題來自花旗的 Andrew Baum。

A couple of questions. First, what are your expectations that you'll need 2 shots of Omicron as opposed to one? The reason I ask is recently published animal models suggest that one Omicron mRNA vaccine actually generates lower levels of neutralizing antibody against Omicron than the ancestral spike variant, presumably due to antigenic sin. It obviously has implications for both revenues in terms of 2 shots but also compliance. And then second, perhaps you could comment on the outlook for CD47 and talk to the differences between your molecule and Gilead's, which obviously has run into some safety issues with the trial suspension.

幾個問題。首先，您對 Omicron 需要 2 次而不是 1 次的期望是什麼？我問的原因是最近發表的動物模型表明，一種 Omicron mRNA 疫苗實際上產生的針對 Omicron 的中和抗體水平低於祖先的穗變體，可能是由於抗原性罪。它顯然對 2 次拍攝的收入以及合規性都有影響。其次，也許您可以評論 CD47 的前景，並談談您的分子與吉利德的分子之間的差異，這顯然在試驗中止時遇到了一些安全問題。

Yes. I will take the first one very quickly, so that I can give time to Mikael to speak about the second one. Look, we have to wait to see the results. But I don't think it is all mRNA vaccines are the same. So I don't think we should extrapolate preclinical data for one effort to what will be the clinical, let's say, results of the other efforts. We are testing both, one sort, we are testing 2 sorts. We are testing pretty soon hybrid vaccines. But everything that we have seen so far give us confident that we will have a very strong reaction and immunogenicity of an Omicron -- against Omicron. But of course, that's based on preclinical. We need to wait to see the first clinical data so that this assumption can be validated. With that, Mikael, what about the Gilead? And by the way, also, Andrew, you said what about your expectations. Our expectations are not based on one sort or 2 sorts or 5 sorts, our expectation is, as I said, it is contract signed as per last week with Comirnaty. So what we'll sign further on will be in addition to whatever we have given so far. Mikael, on the Gilead.

是的。我會很快拿第一個，這樣我就可以給 Mikael 時間來談談第二個。看，我們必須等著看結果。但我不認為所有的 mRNA 疫苗都是一樣的。所以我認為我們不應該將一項努力的臨床前數據外推到其他努力的臨床結果。我們正在測試兩者，一種，我們正在測試兩種。我們很快就會測試混合疫苗。但是到目前為止，我們所看到的一切都讓我們相信，我們將對 Omicron 產生非常強烈的反應和免疫原性——針對 Omicron。但當然，這是基於臨床前的。我們需要等待看到第一個臨床數據，以便驗證這個假設。有了這個，米凱爾，基列呢？順便說一句，安德魯，你也說了你的期望。我們的期望不是基於一種或兩種或 5 種，我們的期望是，正如我所說，它是根據上週與 Comirnaty 簽訂的合同。因此，我們將進一步簽署的內容將是我們迄今為止所提供的內容之外的內容。米凱爾，在基列。

Yes, the interest in our product from Trillium was triggered by its unique design. It is what we call a receptor fusion blocker protein in contrast to magrolimab that you referred to that's on hold. The Gilead antibody, it binds with a lower affinity to the target, and that was by purpose to allow it particularly to accumulate on high-expressing cancer cells and less accumulate on red blood cells to cause -- not to cause anemia or hemolytic anemia.

是的，我們對 Trillium 產品的興趣是由其獨特的設計引起的。它就是我們所說的受體融合阻滯劑蛋白，與您提到的被擱置的 magrolimab 形成對比。吉利德抗體以較低的親和力與靶標結合，其目的是使其特別積聚在高表達的癌細胞上，並減少在紅細胞上的積聚以引起 - 不引起貧血或溶血性貧血。

And indeed, in our studies that have generated proof of concept, we have seen single-agent activity in blood cancers with basically negligible effect on red blood cells. So this is playing well out. We do not know why magrolimab is on clinical hold. But of course, this differentiation that we have in our molecule may be one example of why our molecule has been doing so well thus far. While we initially focus on lymphoid malignancies of the B cell type, we think we also may become increasingly interested in to go to the myeloid space where magrolimab has been, AML and MDS, particularly if our profile now may be superior, and we're waiting readout from such studies also. So for us, the Trillium deal is delivering on all what we expected and may actually have upside due to its more unique profile.

事實上，在我們已經產生概念證明的研究中，我們已經看到單藥在血癌中的活性，對紅細胞的影響基本上可以忽略不計。所以這玩得很好。我們不知道為什麼 magrolimab 處於臨床擱置狀態。但是，當然，我們在分子中的這種差異化可能是為什麼我們的分子迄今為止表現如此出色的一個例子。雖然我們最初專注於 B 細胞類型的淋巴惡性腫瘤，但我們認為我們也可能越來越有興趣進入 magrolimab 曾經存在的骨髓空間、AML 和 MDS，特別是如果我們現在的概況可能更好，而且我們正在也在等待此類研究的讀數。因此，對我們而言，Trillium 交易實現了我們的所有預期，並且由於其更獨特的形象，實際上可能有上行空間。

Your next question comes from Chris Schott from JPMorgan.

您的下一個問題來自摩根大通的 Chris Schott。

Maybe just to start with on -- just some clarifications around guidance. I know you're not giving a lot of details around core versus COVID-related earnings this year, but there's a lot of questions on that front. But if I just take the low end of your sales range at $45 billion, apply a 40% margin, tax adjust that, I think I may get a number somewhere around $2.60 per share at the low end. Is there any issues with that math I'm doing? Or am I in the right ballpark there, if I just want to think about the low end of core guidance for this year?

也許只是開始 - 只是對指導的一些澄清。我知道你沒有提供很多關於今年核心收益與 COVID 相關收益的細節，但在這方面存在很多問題。但是，如果我只是將您的銷售範圍的低端設為 450 億美元，應用 40% 的利潤率，並進行稅收調整，我想我可能會在低端得到一個大約每股 2.60 美元的數字。我正在做的數學有什麼問題嗎？或者如果我只想考慮今年核心指導的低端，我是否處於正確的位置？

My second question was on Paxlovid, and you're referencing here typical small molecule, I guess, gross margins for this one. Just help us frame that a bit more. I guess is something in the mid-80s a reasonable level to think about for gross margins for this product? Or is it substantially higher or lower? I'm just trying to better understand profitability as we maybe think about some of these contracts coming forward this year and maybe that Paxlovid number moving.

我的第二個問題是關於 Paxlovid，我想你在這裡指的是典型的小分子，我猜是這個小分子的毛利率。只是幫助我們更多地構建它。我想在 80 年代中期考慮這個產品的毛利率是否合理？還是顯著更高或更低？我只是想更好地了解盈利能力，因為我們可能會考慮今年即將推出的一些合同，也許 Paxlovid 的數字會發生變化。

And then just a final one, just to wrap up. I'm still trying to get my hands around the BD side of the business and kind of the approach. I guess should we be thinking about a significantly different approach to business development for Pfizer today versus what the company was doing 2 or 3 years ago prior to the COVID upside? Or is this more just a continuation of, I guess, the focus on what you were looking at if we're thinking back to like 2019 as an example?

然後只是最後一個，只是為了結束。我仍在嘗試了解業務的 BD 方面和方法。我想我們是否應該為輝瑞考慮一種與 2 或 3 年前在 COVID 上行之前的業務發展截然不同的方法？或者，我想，如果我們以 2019 年為例，這僅僅是對您所關注內容的關注的延續嗎？

Yes. I'll take very quickly the third one, and then Frank can take the first 2 questions. I wouldn't -- I would say it is a continuation, but with a way more accelerated pace. I don't think we are changing what we're saying since 2019. We are going into the science, as Aamir said. We are going into areas that we think we'll make fewer mistakes in selecting the right targets. We will be more successful, so we will be able to meet at least the success rates of the industry. Our aim is to exceed them.

是的。我會很快回答第三個問題，然後弗蘭克可以回答前兩個問題。我不會 - 我會說這是一個延續，但速度更快。我不認為自 2019 年以來我們正在改變我們所說的內容。正如 Aamir 所說，我們正在進入科學領域。我們正在進入我們認為在選擇正確目標時會犯更少錯誤的領域。我們會更成功，所以我們至少能夠達到行業的成功率。我們的目標是超越他們。

As we are selecting assets, we prefer to go to areas that we can add value. And there are significant areas that we can add value by becoming the preferred partner of several biotechs. And also, we have seen, as Aamir said, that some of the best deals we have done, were not the most capital-intensive deals, right? So there are -- so all of that, we are learning. We are not going to relax the discipline that we are having in selecting, but we are going to intensify a lot our activity in that area. Because, of course, we think that now is the time science is at the stage that we can find enough targets to be able to add value and create value. So that's on the BD side.

當我們選擇資產時，我們更喜歡去我們可以增加價值的領域。通過成為多家生物技術公司的首選合作夥伴，我們可以在很多重要領域增加價值。而且，正如阿米爾所說，我們已經看到，我們所做的一些最好的交易，並不是資本最密集的交易，對吧？所以有 - 所以所有這些，我們正在學習。我們不會放鬆我們在選擇方面的紀律，但我們將加強我們在該領域的活動。因為，當然，我們認為現在是科學處於可以找到足夠的目標以增加價值和創造價值的階段。所以這是在BD方面。

Now Frank, a lot of financial questions for margins, guidance, et cetera.

現在弗蘭克，很多關於利潤、指導等的財務問題。

Sure. So Chris, on the walk through you did on the, I'll call it, the business, excluding Comirnaty and Paxlovid. I would use the midpoint on the revenue. You used, I think, a 40% income before tax margin. And then you got to tax effect that. I didn't hear you say tax effected. So if you do the math, you do the walk through and then you tax effect it, obviously, dividing that by shares outstanding, that will give you, I think, a number that's in the ballpark.

當然。所以克里斯，在你做的過程中，我稱之為業務，不包括 Comirnaty 和 Paxlovid。我會使用收入的中點。我認為你使用了 40% 的稅前收入。然後你必須對它徵稅。我沒有聽到你說稅收影響。因此，如果您進行數學計算，然後進行演練，然後對其徵稅，顯然，將其除以流通股，我認為這將為您提供一個大致上的數字。

On Paxlovid gross margin, let me answer the question this way. One, because we don't give margin information by individual product, right? It's something that for many reasons, we don't do. But the way to think about it is, one, that the income before tax margin on that, the margin profile is similar to our other solid oral dose products. And remember, when you look at the gross margin, there's going to be SI&A investment in Paxlovid this year because we're launching that product. There's additional R&D investment product that year because we're continuing obviously to evolve that product.

關於 Paxlovid 毛利率，讓我這樣回答這個問題。一，因為我們不按單個產品提供保證金信息，對嗎？出於多種原因，我們不這樣做。但思考的方式是，第一，稅前收入利潤率，利潤率概況與我們的其他固體口服劑量產品相似。請記住，當您查看毛利率時，今年將對 Paxlovid 進行 SI&A 投資，因為我們正在推出該產品。那一年還有額外的研發投資產品，因為我們顯然正在繼續發展該產品。

All of that obviously is captured in the income before tax margin on that business, which is similar to our other solid oral dose products. It's all factored in our guidance.

所有這些顯然都反映在該業務的稅前利潤中，這與我們的其他固體口服劑量產品相似。這一切都在我們的指導中。

The one place where you can really see the impact, and hopefully, this is helpful, if you look at our cost of sales as a percentage of revenue last year for the full year, 37.7%. If you look at our guidance this year, 32.2% to 34.2%, the midpoint is 33.2%, that's down at the midpoint, 4.5%, most of which is being driven by the Paxlovid revenue this year. So maybe that's a way to help you in terms of just how to work the numbers.

如果您查看我們去年全年的銷售成本佔收入的百分比 37.7%，那麼您可以真正看到影響的地方，希望這會有所幫助。如果你看一下我們今年的指導，從 32.2% 到 34.2%，中間值為 33.2%，低於中間值 4.5%，其中大部分是由今年 Paxlovid 收入推動的。所以也許這是一種在如何處理數字方面幫助你的方法。

Thank you, Frank.

謝謝你，弗蘭克。

Your next question comes from Chris Shibutani from Goldman Sachs.

您的下一個問題來自高盛的 Chris Shibutani。

Two questions. One, again, just to make sure I understand clearly the thinking about what underpins the intermediate growth expectation through '25. I believe when that was originally issued back in 2019, that did not assume contribution from business development to achieve that CAGR of 6% to '25. Is that still the case? That would be the first question.

兩個問題。再次，只是為了確保我清楚地理解對 25 年中期增長預期的支撐因素的思考。我相信當它最初在 2019 年發佈時，並沒有假設業務發展對實現 25 年 6% 的複合年增長率的貢獻。還是這樣嗎？那將是第一個問題。

And then the second question relates to Paxlovid. We have the standard-risk study that you've modified expanding. Can you talk about what kind of result we would need to see in order to influence the kind of decisions and discussions that Angela is having with governments? In particular, the primary end point, which just missed statistical significance on the alleviation of symptoms, do you need to hit that? Or are the discussions being guided around the ability to meet the secondary end point, which was the decreased risk of hospitalizations in severe disease from that standard-risk study?

然後第二個問題與 Paxlovid 有關。我們有您修改擴展的標準風險研究。您能否談談我們需要看到什麼樣的結果才能影響安吉拉與政府的決策和討論？尤其是主要終點，它在緩解症狀方面錯過了統計學意義，你需要達到那個嗎？還是圍繞滿足次要終點的能力展開討論，即標準風險研究中嚴重疾病住院風險的降低？

Yes. And maybe I can take both in the interest of time. I can confirm that our guidance for 6% was excluding BD. So that was from '19 all the way to '25, 6% CAGR from the things that we had at that time.

是的。也許我可以考慮時間。我可以確認我們對 6% 的指導不包括 BD。所以從 19 年一直到 25 年，我們當時擁有的東西的複合年增長率為 6%。

As regards the standard-risk primary end point, I think most of the governments, if not all, they are focusing right now all their purchases and their discussions that we are having on the ability to reduce hospitalizations. And by the way, most of the -- I mean, FDA, for example, has already approved vaccinated and unvaccinated, which is included -- that means that includes also people that were in the standard-risk population because the high-risk population were all unvaccinated. So if we go -- the standard risk, I think, will contribute. But I think everybody is moving with the assumption that we give it to all people to prevent hospitalization. That's the main -- and that's the main thing that everybody is looking.

至於標準風險的主要終點，我認為大多數政府（如果不是全部的話）現在都將注意力集中在他們所有的採購和討論上，我們正在討論減少住院的能力。順便說一句，大多數——我的意思是，例如，FDA 已經批准了接種疫苗和未接種疫苗的人，包括在內——這意味著還包括標準風險人群中的人，因為高風險人群都沒有接種疫苗。所以如果我們去 - 我認為標準風險將有所貢獻。但我認為每個人都在假設我們將其提供給所有人以防止住院。這是主要的——這是每個人都在關注的主要事情。

Now the in-house contract, it is very different. And I can say it's very much the landscape. There are no discussions around that right now. But if it comes positive, clearly, that could be used also in preventing infections in high-risk populations when someone in the household or in the senior house or in other, let's say, business -- in other settings that people are living together, one is getting infected. But this is something that will come on top of any discussions that we are having right now, if it is positive.

現在的內部合同，就大不一樣了。我可以說這是非常風景。目前沒有圍繞這方面的討論。但是，如果它是積極的，很明顯，這也可以用於預防高危人群的感染，當有人在家庭或高級住宅或其他，比方說，商業 - 在人們共同生活的其他環境中，一個正在被感染。但這將是我們目前正在進行的任何討論的基礎，如果它是積極的。

The next question comes from Vamil Divan from Mizuho Securities.

下一個問題來自瑞穗證券的 Vamil Divan。

I guess I'll stick with the same theme around Paxlovid and business development. So first on Paxlovid, just to make sure we're all starting on the same page, I guess. Can you comment exactly how many doses are included in the guidance that you're giving right now? You mentioned in the release the 20 million to the U.S., I think 2.75 million to the U.K. So obviously, there's been some other contracts that have been signed. So I don't know if you can give us a number or a range just so we have a sense of kind of what's included right now.

我想我會圍繞 Paxlovid 和業務發展堅持相同的主題。所以首先在 Paxlovid 上，只是為了確保我們都從同一個頁面開始，我猜。您能否準確評論您現在提供的指導中包含多少劑量？你在發布中提到了 2000 萬到美國，我認為 275 萬到英國。所以很明顯，還有一些其他的合同已經簽署。所以我不知道你是否可以給我們一個數字或一個範圍，以便我們對現在包含的內容有所了解。

And then on business development, I just thought one thing that's sort of interesting when you're talking about Slide 13. Albert, you mentioned the strength of your balance and cash flow has allowed you to pursue new BD opportunities going forward that could add at least $25 billion of risk-adjusted revenues for 2030. And I'm just curious, that $25 billion is sort of a specific number. I'm wondering sort -- obviously, this is in your prepared remarks. So I'm sure it was well thought out. So I'm just curious what sort of drove that. Obviously, the number could be much smaller or probably a lot bigger depending on what you do over the next few years. So maybe you can just provide some clarity on why you worded that the way you did.

然後在業務發展方面，當您談論幻燈片 13 時，我只是想到了一件有趣的事情。阿爾伯特，您提到您的餘額和現金流的優勢使您能夠追求新的 BD 機會，這可能會增加2030 年風險調整後的收入至少為 250 億美元。我很好奇，250 億美元是一個特定的數字。我想知道排序 - 顯然，這是在你準備好的評論中。所以我確信這是經過深思熟慮的。所以我只是好奇是什麼驅動的。顯然，這個數字可能要小得多，也可能要大得多，這取決於你在接下來的幾年裡做什麼。所以也許你可以澄清一下你為什麼要這樣說。

Why we selected $25 billion -- to speak about $25 billion, you mean?

為什麼我們選擇 250 億美元——你的意思是說 250 億美元？

Yes, saying at least $25 billion in adjusted revenues.

是的，至少 250 億美元的調整後收入。

Yes. I got it. Frank, would you like to take the Paxlovid and the doses?

是的。我知道了。弗蘭克，你想服用 Paxlovid 和劑量嗎？

Of course. So Vamil, on the Paxlovid guidance, you heard Angela mentioned before, we're very active right now, 100-plus negotiations with different governments. We don't want to put any information out there that could, I'll call it, lead to misleading assumptions, and those assumptions being detrimental to those contract negotiations.

當然。所以 Vamil，關於 Paxlovid 的指導，你聽說過 Angela 之前提到過，我們現在非常活躍，與不同的政府進行了 100 多次談判。我們不想公開任何可能導致誤導性假設的信息，而這些假設對合同談判有害。

But now you mentioned a couple of contracts that have been announced and publicly and where the dose information was included. You mentioned the U.S., 20 million; the U.K., 2.75 million. If you look at everything we've announced publicly, give or take, it's about 30 million treatments. And so that 30 million treatments is clearly included in the guidance that we provided in the $22 billion revenue.

但現在你提到了一些已經公開宣布的合同，其中包括劑量信息。你提到美國，2000萬；英國，275 萬。如果你看看我們公開宣布的一切，給予或接受，大約有 3000 萬次治療。因此，我們在 220 億美元的收入中提供的指導中明確包含了 3000 萬種治療方法。

Thank you. And Aamir, why you selected $25 billion?

謝謝你。還有阿米爾，你為什麼選擇 250 億美元？

Sure. So Vamil, a couple of thoughts. One, we obviously -- between the strength of our balance sheet and the cash flows, we have the ability to deploy significant capital. And going beyond our growing dividend, we think that those cash flows deployed into business development are going to give us an attractive return. So that's one piece of it.

當然。所以 Vamil，有幾個想法。一，我們顯然——在我們的資產負債表和現金流之間，我們有能力部署大量資本。除了我們不斷增長的股息之外，我們認為那些部署到業務發展中的現金流將為我們帶來誘人的回報。所以這是其中的一部分。

The second is we think that this is, frankly, a great time for scientific advancement in our industry. As you look across academia, venture biotech, big, small, there's no shortage of external substrate that we think can complement what we're doing internally. And we're going to be thoughtful and disciplined about the science that we want to pursue. And the combination of those 2 things, combined with the capabilities that we have, we think that there is significant growth that we can add to our business through business development going forward.

其次，坦率地說，我們認為這是我們行業科學進步的好時機。縱觀學術界，風險生物技術，大大小小的，不乏我們認為可以補充我們內部工作的外部基質。我們將對我們想要追求的科學進行深思熟慮和自律。這兩件事的結合，再加上我們擁有的能力，我們認為我們可以通過未來的業務發展為我們的業務增加顯著的增長。

Yes. And also, it is very important also to understand, Vamil, that we believe that once you put a target, you better execute way better when you have a target in front of you. And actually, we believe that the target needs to be public because we're a public company, and we don't have a problem to do it.

是的。此外，Vamil 了解一下也很重要，我們相信一旦你設定了一個目標，當你面前有一個目標時，你會更好地執行。實際上，我們認為目標需要公開，因為我們是一家上市公司，這樣做沒有問題。

So also, we went in to analyze the substrate and the opportunity. And as always, we are providing at least $25 billion because, as always, we like to have targets that we are putting out there, and we are beating them. But we believe that with the current -- our analytics that we have done, this is a very reasonable target to achieve without, let's say, utilizing all of our fire power right now. So that will allow us to do dividend and other uses of capital and still do that. And we are confident to put it out there so that people can start measuring against it. Thank you very much.

因此，我們也進去分析了底物和機會。和往常一樣，我們提供至少 250 億美元，因為一如既往，我們希望有我們提出的目標，並且我們正在擊敗它們。但是我們相信，就目前我們所做的分析而言，這是一個非常合理的目標，可以在不利用我們所有的火力的情況下實現。因此，這將使我們能夠進行股息和資本的其他用途，並且仍然可以這樣做。我們有信心把它放在那裡，這樣人們就可以開始衡量它。非常感謝你。

Your next question comes from Kerry Holford from Berenberg.

您的下一個問題來自 Berenberg 的 Kerry Holford。

So firstly, just on the oral GLP-1. I wonder if you can confirm the number of pills per day that you'll be using in your Phase 2b study up to that maximum dose of 200 mg per -- twice a day. What's the pill burden for the highest dose?

所以首先，就口服 GLP-1。我想知道您是否可以確認您在 2b 期研究中每天使用的藥片數量，最大劑量為 200 毫克/天 - 每天兩次。最高劑量的藥丸負擔是多少？

And also on obesity, you've not discussed that today. But do you have the Phase 2a data in-house? I noted that you said you've moved another oral GLP-1 molecule into the clinic. And I'm just interested to know how that asset may differ from the initial danuglipron?

還有關於肥胖，你今天還沒有討論過。但是你有內部的 2a 階段數據嗎？我注意到你說你已經將另一種口服 GLP-1 分子轉移到診所。我只是想知道該資產與最初的 danuglipron 有何不同？

And then lastly, just on the guidance. So if I'm thinking about your $4 billion sort of range on your sales guidance, given you've given us the point estimates or thereabouts for the vaccine and the antiviral, should I assume the majority of the flex remaining relates to the base business? And if so, can you help me understand the key moving parts within that element of the business? Which drugs may be a driver of that flex?

最後，只是關於指導。因此，如果我正在考慮你們 40 億美元的銷售指導範圍，鑑於你們已經給我們提供了疫苗和抗病毒藥物的點估計或附近，我是否應該假設剩餘的大部分彈性與基礎業務有關?如果是這樣，您能否幫助我了解該業務要素中的關鍵移動部分？哪些藥物可能是這種彈性的驅動因素？

Thank you, Kerry. Let me take very quickly in the interest of time, the last one. No, the flex is spread around everything. So you should assume, for example, in the $31 billion of -- in the $32 billion that we gave -- for $33 billion, right, on the vaccines, $500 million down, that's $1 billion on the Paxlovid, $500 million -- not $500 million. That's another $1 billion. And then on the business, as always, we gave $1 billion, up and down. So whatever you think is the midpoint, $1 billion up, which is consistent with what we were doing all these years for that level of business.

謝謝你，克里。考慮到時間，讓我很快採取最後一個。不，彈性分佈在所有東西上。所以你應該假設，例如，在 310 億美元中 - 在我們提供的 320 億美元中 - 330 億美元，對，疫苗，5 億美元，Paxlovid 的 10 億美元，5 億美元 - 不是5億美元。這又是 10 億美元。然後在業務上，我們一如既往地上下捐贈了 10 億美元。因此，無論您認為中點是什麼，10 億美元以上，這與我們這些年來為該級別業務所做的工作是一致的。

And Mikael, on the oral, do you want...

Mikael，在口頭上，你想要...

Danuglipron is a BID drug and pill burden will be relatively low. You also asked for the additional GLP-1 drug we have in clinical development. That's a once a day drug. As we have now, I think, really defined what will be soon optimal titration for an oral GLP-1, and we were, of course, pioneering that, there isn't really data on it. We may actually consider to take the once daily in the same study of danuglipron, given that we have now this unique opportunity to look through what seems to be 2 great drugs. But currently, I believe danuglipron has all what it takes to go forward to a potential pivotal study based on this study that we shared with you. But it's, of course, a unique situation to have more than one molecule, and it gives us the very best option for going into Phase 3 quite rapidly after concluding that Phase 2b, pending, of course, expected outcome.

Danuglipron 是一種 BID 藥物，藥丸負擔相對較低。您還要求提供我們在臨床開發中的其他 GLP-1 藥物。那是一天一次的藥。我認為，正如我們現在所擁有的那樣，真正確定了口服 GLP-1 的最佳滴定度，當然，我們是開創性的，沒有關於它的真正數據。實際上，我們可能會考慮在同一項研究中每天服用一次 danuglipron，因為我們現在有這個獨特的機會來研究似乎是兩種偉大的藥物。但目前，我相信 danuglipron 擁有一切必要條件，可以根據我們與您分享的這項研究開展一項潛在的關鍵研究。但是，當然，擁有多個分子是一種獨特的情況，它為我們提供了在結束第 2b 階段之後非常迅速地進入第 3 階段的最佳選擇，當然，還有待預期的結果。

Thank you, Mikael. And the last question, please.

謝謝你，米凱爾。最後一個問題，請。

Your final question comes from the line of Carter Gould from Barclays.

您的最後一個問題來自 Barclays 的 Carter Gould。

I'll keep it to one since we're at the end. And at the risk of not getting an answer, on OUS pricing for Paxlovid, I understand the underlying aspect is driving sort of your pricing strategy between GDP and the volume-based discounts. But in practice, how consistent has the pricing been across geographies? Any color at a high level would be helpful. And as we think about potentially the standard-risk data, the prophy data kind of playing out over the course of the year, should we anticipate that pricing will be relatively consistent per course in the second half relative to the first half? Any color there would be helpful.

我會保持一個，因為我們已經結束了。冒著沒有得到答案的風險，關於 Paxlovid 的 OUS 定價，我理解潛在的方面是推動你在 GDP 和基於數量的折扣之間的定價策略。但在實踐中，不同地區的定價有多一致？任何高級別的顏色都會有所幫助。當我們考慮到潛在的標準風險數據，即在一年中出現的預防數據時，我們是否應該預期下半年每門課程的定價將相對於上半年相對一致？那裡的任何顏色都會有幫助。

Our pricing for Paxlovid is a tier pricing. So there is a tier for high-income countries, and that is more or less in line with what you have seen published for Merck's, for example, product, and we have seen published ourselves. Only exception was in the U.S., that they got a very special price because of higher orders, but the rest are more or less consistent.

我們對 Paxlovid 的定價是分級定價。因此，高收入國家有一個等級，這或多或少與您看到的默克公司發布的內容一致，例如產品，我們自己也看到發布。唯一的例外是在美國，因為訂單量大，他們得到了一個非常特別的價格，但其餘的或多或少是一致的。

And then there is, of course, there is a second tier for middle-income countries. And for the lower-income countries, we are going to provide it at cost. But also for the low-income countries, in addition to our own providing at cost, of course, we have also initiated a process that a very big number of generic companies will start manufacturing for the low-income countries, which will be 53% of the global population.

當然，中等收入國家還有第二層。對於低收入國家，我們將按成本提供。但是對於低收入國家，除了我們自己按成本提供，當然，我們也啟動了一個流程，非常多的仿製藥公司將開始為低收入國家生產，這將是 53%全球人口。

Now if the price will remain consistent, clearly, this is nothing to comment here. We will not, let's say, commenting on how prices may or may not evolve in the future.

現在，如果價格將保持一致，顯然，這裡沒有什麼可評論的。比方說，我們不會評論未來價格可能會或可能不會發生變化。

Thank you very much. Now some closing comments very quickly. We have generated strong results, of course, for both pace and impact and financial performance, and we look forward to continue that in 2022. I want to speak a little bit about a few changes in people that we are doing.

非常感謝你。現在很快就結束了一些評論。當然，我們在步伐、影響和財務業績方面都取得了強勁的成果，我們期待在 2022 年繼續保持這種勢頭。我想談談我們正在做的一些人的變化。

Speaking about that, we continue to attract visionary, purpose-driven leaders, with a track record of delivering breakthrough results for patients. Case in point, last week, we announced that Dr. William Pao will join Pfizer as Executive Vice President and Chief Development Officer, effective March 21 of this year. Dr. Pao brings more than 25 years of experience as an oncologist and scientist. He joins us from Roche, where he most recently served as the Head of Pharma Research and Early Development. He oversaw the discovery and early development of a portfolio of new molecular entities to treat diseases related to cancer, neuroscience, ophthalmology, rare diseases and can go on and on and on. Of course, cancer is a very big part of his portfolio.

說到這一點，我們繼續吸引有遠見、目標導向的領導者，他們在為患者提供突破性成果方面有著良好的記錄。例如，上週，我們宣布 William Pao 博士將加入輝瑞，擔任執行副總裁兼首席開發官，自今年 3 月 21 日起生效。 Pao 博士擁有超過 25 年的腫瘤學家和科學家經驗。他從羅氏加入我們，最近擔任藥物研究和早期開發負責人。他監督了一系列新分子實體的發現和早期開發，以治療與癌症、神經科學、眼科、罕見疾病相關的疾病，並且可以繼續下去。當然，癌症是他投資組合中非常重要的一部分。

Clearly, I want to mention that Dr. Pao succeeds Rod MacKenzie, a legendary leader in Pfizer, who recently announced his intent to retire after 35 years with Pfizer. I want to thank Rod for his incredible contribution to Pfizer, including the outstanding leadership in helping bring Comirnaty and Paxlovid to the world so quickly.

顯然，我想提一下，鮑博士接替了輝瑞的傳奇領導人羅德·麥肯齊，後者最近宣布打算在輝瑞工作 35 年後退休。我要感謝 Rod 為輝瑞做出的令人難以置信的貢獻，包括在幫助 Comirnaty 和 Paxlovid 如此迅速地推向世界方面的傑出領導。

Of course, also, I need to touch base on something that everybody has in mind. I want to take a moment to recognize my trusted colleague and friend, Frank D'Amelio, who also has announced his intention to retire from Pfizer after an incredibly impactful decade and a half with the company as CFO. Frank is one of the smartest, more respected and most effective leaders I have ever had the good fortune to work with, and the positive impact he has had on Pfizer and on all our stakeholders is immeasurable.

當然，我也需要觸及每個人都想到的東西。我想花點時間認識一下我值得信賴的同事和朋友弗蘭克·達梅里奧（Frank D'Amelio），他也宣布打算在輝瑞公司擔任首席財務官 15 年之後從輝瑞公司退休。弗蘭克是我有幸與之共事的最聰明、最受尊敬和最有效的領導者之一，他對輝瑞公司和我們所有利益相關者的積極影響是無法估量的。

Frank isn't going anywhere yet, just to clarify, as he has agreed to stay on board and as we search for his successor and also to serve in a consulting role through the transition. That said, I wanted to take the opportunity to thank him publicly for all he has meant to Pfizer and to me personally. And Frank, on behalf of our 80,000 colleagues around the world, I wish you good health, every happiness as you begin a new chapter when this time comes, because it's not yet. Wherever life's journey takes you, I'm sure it will be directionally correct.

弗蘭克還沒有去任何地方，只是為了澄清一下，因為他已同意留在董事會，我們正在尋找他的繼任者，並在過渡期間擔任諮詢角色。也就是說，我想藉此機會公開感謝他對輝瑞和我個人的一切意義。弗蘭克，我代表我們在世界各地的 80,000 名同事，祝你們身體健康，祝你們幸福快樂，因為現在還沒有開始新的篇章。無論人生的旅程將你帶到哪裡，我相信它的方向都是正確的。

And that will bring an end to our call. Thank you for joining us.

這將結束我們的呼籲。感謝您加入我們。

Have a great rest of your day.

好好休息一天。

Ladies and gentlemen, this does conclude Pfizer's Fourth Quarter 2021 Earnings Conference Call. You may now all disconnect.

女士們先生們，輝瑞公司 2021 年第四季度財報電話會議就此結束。您現在可以全部斷開連接。