Novavax Inc (NVAX) 2021 Q4 法說會逐字稿

Ladies and gentlemen, thank you for standing by, and welcome to the Novavax Fourth Quarter and Full Year 2021 Financial Results and Operational Highlights Conference Call. (Operator Instructions) Please also be advised that today's conference call is being recorded. (Operator Instructions) I would now like to hand the conference call over to your speaker today, Silvia Taylor. You may begin.

女士們，先生們，感謝您的支持，並歡迎參加 Novavax 2021 年第四季度和全年財務業績和運營亮點電話會議。 （操作員說明）還請注意，今天的電話會議正在錄製中。 （操作員說明）我現在想將電話會議交給你今天的演講者，西爾維婭·泰勒。你可以開始了。

Good afternoon, and thank you all for joining us today to discuss our fourth quarter and full year 2021 operational highlights and financial results. A press release announcing our results is currently available on our website at novavax.com, and an audio archive of this conference call will be available on our website later today.

下午好，感謝大家今天加入我們，討論我們的第四季度和 2021 年全年運營亮點和財務業績。宣布我們結果的新聞稿目前可在我們的網站 novavax.com 上獲得，本次電話會議的音頻檔案將於今天晚些時候在我們的網站上提供。

Before we begin with prepared remarks, I need to remind you that we will be making forward-looking statements during this teleconference, which are based on our current expectations and beliefs. For example, statements relating to future financial or business performance, conditions or strategy including expectations regarding revenue, operating expenses, cash usage, clinical development of our vaccine candidates, timing of future regulatory filings, authorizations and actions and other anticipated milestones are forward-looking statements. Novavax cautions that these forward-looking statements are subject to numerous assumptions, risks and uncertainties which change over time, and actual results could differ materially from what is described in such statements. We encourage you to consult the risk factors discussed in our SEC filings for additional detail.

在開始準備發言之前，我需要提醒您，我們將在本次電話會議期間根據我們當前的期望和信念做出前瞻性陳述。例如，與未來財務或業務業績、條件或戰略有關的陳述，包括對收入、運營費用、現金使用、我們候選疫苗的臨床開發、未來監管備案的時間、授權和行動以及其他預期里程碑的預期，都是前瞻性的陳述。 Novavax 告誡說，這些前瞻性陳述受到許多假設、風險和不確定性的影響，這些假設、風險和不確定性會隨著時間的推移而變化，實際結果可能與此類陳述中的描述存在重大差異。我們鼓勵您查閱我們提交給美國證券交易委員會的文件中討論的風險因素以獲取更多詳細信息。

Joining me today is Stan Erck, President and CEO, who will provide an overview of recent achievements, discuss regulatory updates and preview our upcoming strategic priorities; additionally, John Trizzino, Chief Commercial Officer and Chief Business Officer, will provide an update on the status of our global COVID-19 vaccine rollout, supply and manufacturing as well as address the broader market opportunity for our COVID-19 vaccine; Dr. Filip Dubovsky, Chief Medical Officer, will discuss recent clinical development across our pipeline; and Jim Kelly, Chief Financial Officer and Treasurer, will provide an overview of our financial results. Dr. Greg Glenn, President of Research and Development, will also be available for the Q&A section at the end of today's call.

今天加入我的是總裁兼首席執行官 Stan Erck，他將概述最近的成就，討論監管更新並預覽我們即將到來的戰略重點；此外，首席商務官兼首席商務官 John Trizzino 將提供我們全球 COVID-19 疫苗推出、供應和製造狀態的最新信息，並為我們的 COVID-19 疫苗提供更廣泛的市場機會；首席醫療官 Filip Dubovsky 博士將討論我們管道中最近的臨床開發；首席財務官兼財務主管 Jim Kelly 將概述我們的財務業績。研發總裁 Greg Glenn 博士也將在今天電話會議結束時參加問答環節。

I would now like to hand the call over to Stan. Please turn to Slide 4. Stan?

我現在想把電話交給斯坦。請翻到幻燈片 4。斯坦？

Thanks, Silvia, and thanks, everyone, for joining us today as we discuss the substantial progress made by Novavax in 2021 and into the beginning of 2022. Through continued execution across all areas of our business, today, we have rapidly transitioned into a global commercial company, now delivering our COVID-19 vaccine throughout the world.

感謝 Silvia，感謝大家今天加入我們，討論 Novavax 在 2021 年和 2022 年初取得的重大進展。通過在我們業務的所有領域持續執行，今天，我們已迅速轉變為全球商業公司，現在在世界各地提供我們的 COVID-19 疫苗。

Since making our first submission for our authorization in August of last year, we've delivered upon all of our commitments across our entire business, including, in regulatory, we have authorizations today from 12 regulatory agencies as well as emergency use listing from the World Health Organization, rapidly expanding access to our COVID-19 vaccine. We are authorized in 38 countries and have emergency use listing from the WHO representing the potential to reach over 170 total countries. Adding this all up, these markets represent 6 billion lives.

自去年 8 月首次提交我們的授權以來，我們已經兌現了我們在整個業務中的所有承諾，包括在監管方面，我們今天獲得了 12 個監管機構的授權以及來自世界的緊急使用清單衛生組織，迅速擴大獲得我們的 COVID-19 疫苗的機會。我們在 38 個國家獲得授權，並擁有來自 WHO 的緊急使用清單，代表著可能覆蓋 170 多個國家。加起來，這些市場代表著 60 億人的生命。

In commercialization, we've initiated the commercial rollout of Nuvaxovid. We have shipped our vaccine to the European Union Australia, Indonesia and South Korea and first doses of our vaccine have now been administered in all of these markets.

在商業化方面，我們已經啟動了 Nuvaxovid 的商業推廣。我們已將疫苗運往歐盟、澳大利亞、印度尼西亞和韓國，我們的第一劑疫苗現已在所有這些市場接種。

Manufacturing capacity, we've achieved our target of annual capacity of more than 2 billion doses with the ability to meet the current and future global demand for our vaccine. And with respect to clinical data, we have built upon our robust data of clinical evidence, robust body of clinical evidence, and we have generated additional data to support expanded indications and policy recommendations that will drive utilization across our 3 core targets, primary vaccinations, boosters and pediatric populations. These include new data we announced today demonstrating protection against all COVID-19 infection and durability of efficacy over 6 months, booster data demonstrating broad cross-reactivity against variants, and adolescent data demonstrating clinical efficacy against variants.

製造能力，我們已經實現了年產能超過 20 億劑的目標，能夠滿足當前和未來全球對我們疫苗的需求。在臨床數據方面，我們建立在我們強大的臨床證據數據、強大的臨床證據基礎之上，並且我們已經生成了額外的數據來支持擴展的適應症和政策建議，這將推動我們三個核心目標的使用，主要疫苗接種，助推器和兒科人群。其中包括我們今天宣布的新數據，這些數據證明了對所有 COVID-19 感染的保護作用和 6 個月以上的療效持久性、證明對變體的廣泛交叉反應性的增強數據，以及證明對變體的臨床療效的青少年數據。

With respect to COVID-19 variants, we also demonstrated our ability to rapidly respond to variants of COVID-19. We developed an Omicron-specific variant vaccine and within weeks of initiating development, we began GMP manufacturing. This serves as an important proof of concept that we can evolve our vaccine as the pandemic evolves with new variants. With all of this momentum over the past 60 days, we are now delivering our protein-based vaccine to the world, and we expect this momentum will only accelerate.

關於 COVID-19 變體，我們還展示了我們快速響應 COVID-19 變體的能力。我們開發了一種 Omicron 特異性變體疫苗，在開始開發的幾週內，我們開始了 GMP 生產。這是一個重要的概念證明，我們可以隨著新變種的大流行演變而進化我們的疫苗。憑藉過去 60 天的所有這些勢頭，我們現在正在向世界提供我們的蛋白質疫苗，我們預計這種勢頭只會加速。

In 2022, we see significant opportunities for Nuvaxovid due to the ongoing urgent need for vaccine globally. These include a global vaccination rate of only 56%, clearly, we have not yet met the WHO goal of 70% global vaccination. Waning immunity over time after vaccination, the continued rise of variants and pent-up demand for additional vaccine options, especially a protein-based option, all of these factors contribute to the urgency of bringing our vaccine to the market.

2022 年，由於全球對疫苗的持續迫切需求，我們看到了 Nuvaxovid 的重大機遇。其中包括僅 56% 的全球疫苗接種率，顯然，我們還沒有達到世界衛生組織 70% 全球疫苗接種率的目標。疫苗接種後隨著時間的推移免疫力下降，變種的持續增加以及對額外疫苗選擇的被壓抑的需求，尤其是基於蛋白質的選擇，所有這些因素都導致我們的疫苗推向市場的緊迫性。

With line of sight into all of these factors informing the need for our vaccine today, for the first time, we are providing financial guidance outlining our expectation to achieve full year 2022 total revenue of between $4 billion and $5 billion.

通過對所有這些因素的了解，我們首次提供了財務指導，概述了我們對 2022 年全年總收入在 40 億至 50 億美元之間的預期。

With that, please turn to Slide 5, where we provide an overview of our regulatory progress to date. Through our focus on expediting our regulatory filings since the first submissions in August 2021, we've now gained authorizations in 38 countries. For our product, Nuvaxovid, we have received authorizations from all 27 member states of the European Union, Great Britain, Canada, Australia, Singapore, New Zealand, the United Arab Emirates, and in partnership with SK Bioscience, we also received approval of our BLA in South Korea.

有了這個，請轉到幻燈片 5，我們在其中概述了我們迄今為止的監管進展。自 2021 年 8 月首次提交以來，我們一直專注於加快監管備案，目前我們已在 38 個國家/地區獲得授權。對於我們的產品 Nuvaxovid，我們已獲得歐盟所有 27 個成員國、英國、加拿大、澳大利亞、新加坡、新西蘭、阿拉伯聯合酋長國的授權，並且與 SK Bioscience 合作，我們還獲得了我們的批准BLA 在韓國。

For COVOVAX, which is our vaccine manufacturer and marketing bio partner in Serum Institute, we received authorizations from India, Indonesia, the Philippines and Bangladesh. For both Nuvaxovid and COVOVAX, we've also received emergency use listing from the World Health Organization, representing the potential for our vaccine to reach more than 130 additional countries. In these geographies, Novavax is the first protein based COVID-19 vaccine authorized for commercial use based on Phase III data, allowing us to bring to the market an important alternative based on a well-understood technology.

COVOVAX 是我們在血清研究所的疫苗製造商和營銷生物合作夥伴，我們獲得了印度、印度尼西亞、菲律賓和孟加拉國的授權。對於 Nuvaxovid 和 COVOVAX，我們還收到了世界衛生組織的緊急使用清單，這表明我們的疫苗有可能到達 130 多個其他國家。在這些地區，Novavax 是第一個根據 III 期數據授權用於商業用途的基於蛋白質的 COVID-19 疫苗，使我們能夠將基於眾所周知的技術的重要替代品推向市場。

With significant regulatory progress made to date, we expect to expand our regulatory authorizations through additional submissions, including making Nuvaxovid available in the United States where we have already filed our request for EUA in January. As Filip will discuss later on today's call, we are also executing upon a robust clinical development program to make our vaccine more widely available.

隨著迄今為止取得的重大監管進展，我們希望通過額外提交來擴大我們的監管授權，包括在美國提供 Nuvaxovid，我們已經在 1 月份提交了 EUA 請求。正如菲利普將在今天的電話會議稍後討論的那樣，我們還在執行一項強有力的臨床開發計劃，以使我們的疫苗更廣泛地可用。

And with that, I'll now hand it over to John to discuss our progress in delivering doses of our vaccine globally.

有了這個，我現在將把它交給約翰來討論我們在全球提供疫苗劑量方面的進展。

Thank you, Stan. Novavax continues to build a body of evidence to enhance our highly competitive Nuvaxovid product profile, which demonstrates high levels of efficacy and a reassuring safety profile. Beginning with our positive Phase III data, we have built upon our clinical package with new data from boosting studies, pediatric populations and today with data demonstrating our vaccine's ability to protect against infection and its strong durability over time.

謝謝你，斯坦。 Novavax 繼續建立大量證據來增強我們極具競爭力的 Nuvaxovid 產品形象，該產品展示了高水平的療效和令人放心的安全性。從我們積極的 III 期數據開始，我們利用來自加強研究、兒科人群的新數據以及今天的數據證明我們的疫苗具有防止感染的能力及其隨著時間的推移具有很強的耐久性，從而建立了我們的臨床數據包。

Taken together, our product profile results in a differentiated vaccine that will help achieve global health policy goals and at the same time, allow us to satisfy existing and future demand globally. As we look to expand access to our vaccine, we've already begun to see supportive policy recommendations for Nuvaxovid, which is a testament to the robust clinical data package we've generated to date.

總而言之，我們的產品簡介產生了一種差異化的疫苗，這將有助於實現全球衛生政策目標，同時使我們能夠滿足全球現有和未來的需求。隨著我們尋求擴大疫苗的使用範圍，我們已經開始看到對 Nuvaxovid 的支持性政策建議，這證明了我們迄今為止生成的強大臨床數據包。

Ministries of health and national immunization technical advisory groups across the European Union at the World Health Organization and in Canada, Australia and Singapore have published their recommendations for Nuvaxovid as a 2-dose primary series. And in some national policy recommendation bodies have recommendations allowing heterologous vaccination and boosting.

世界衛生組織和加拿大、澳大利亞和新加坡的衛生部和國家免疫技術諮詢小組已經發布了他們對 Nuvaxovid 作為 2 劑主要係列的建議。並且在一些國家政策建議機構中有建議允許異種疫苗接種和加強免疫。

With regulatory authorizations and policy recommendations in hand, we've mobilized our global manufacturing and supply network to execute on the rollout of our first commercial product, Nuvaxovid.

憑藉監管授權和政策建議，我們調動了我們的全球製造和供應網絡來執行我們的第一個商業產品 Nuvaxovid 的推出。

Since December of last year, we've begun shipping doses around the world, including 9 million doses to Indonesia, 6 million to Australia, 2 million to South Korea and 27 million doses that have already been delivered to our European distribution center. Shipments are already arriving in individual EU countries, and we expect shipments to continue to additional countries in the EU will quickly follow these initial deliveries.

自去年 12 月以來，我們已開始向全球運送疫苗，其中 900 萬劑發往印度尼西亞，600 萬劑發往澳大利亞，200 萬劑發往韓國，2700 萬劑已運往我們的歐洲配送中心。貨物已經抵達各個歐盟國家，我們預計將繼續向歐盟其他國家的貨物運送，這些貨物將很快跟進這些初始交付。

As already reported, an additional 42 million dose order commitment is in place for the second quarter, resulting in 69 million total doses for Europe in the first half of 2022. In all of these markets, vaccinations with Nuvaxovid have begun.

正如已經報導的那樣，第二季度額外的 4200 萬劑訂單承諾到位，從而導致 2022 年上半年歐洲的總劑量為 6900 萬劑。在所有這些市場中，已經開始使用 Nuvaxovid 進行疫苗接種。

For the COVAX Facility, we are collaborating closely with Gavi and our global partners to optimize supply quantities and delivery schedules. And together, we are committed to achieving our shared goal of equitable access. Now with regulatory authorization in 38 countries and a WHO EUL, our vaccine has the potential to access more than 170 countries around the globe. This global access is supported by bilateral supply agreements already in process of being shipped, License partners, Serum Institute, SK Bio and Takeda, all manufacturing, we expect additional approvals in the U.S. and others with immediate product availability. And through our partnership with Serum Institute, we have already shipped 9 million doses to Indonesia in support of our commitment to equitable access.

對於 COVAX 設施，我們正在與 Gavi 和我們的全球合作夥伴密切合作，以優化供應數量和交付時間表。我們一起致力於實現我們的共同目標，即公平獲取。現在，我們的疫苗獲得了 38 個國家的監管授權和 WHO EUL，有可能進入全球 170 多個國家。這種全球訪問得到了雙邊供應協議的支持，這些協議已經在發貨過程中，許可合作夥伴、血清研究所、SK Bio 和武田，所有製造，我們預計在美國和其他國家獲得更多批准，並立即提供產品。通過與血清研究所的合作，我們已經向印度尼西亞運送了 900 萬劑疫苗，以支持我們對公平獲取的承諾。

In the U.S., we further solidified our partnership by extending our funding agreement through 2023. With this latest modification to our agreement, our $1.8 billion of allotted funding will support additional booster and adolescent booster studies for our vaccine, reflecting the U.S. government's ongoing investment to support expansions of our label. We are appreciative of the ongoing support from the U.S. government, and in the future, we see an opportunity to pursue procurement agreements to supply doses to the U.S.

在美國，我們通過將資助協議延長至 2023 年進一步鞏固了我們的合作夥伴關係。通過對我們協議的最新修改，我們分配的 18 億美元資金將支持我們疫苗的額外加強和青少年加強研究，這反映了美國政府持續投資於支持我們標籤的擴展。我們感謝美國政府的持續支持，並且在未來，我們看到了尋求採購協議以向美國供應劑量的機會。

We are frequently engaged with health ministers, public health authorities and KOLs around the globe, and it is clear that there is a strong demand for an effective protein-based alternative that is safe, effective and refrigerator stable to allow for ease of transport and on-site storage. In addition, as doses of our vaccine are being received across the globe, we believe consumer choice will play an increasingly important role in driving demand.

我們經常與世界各地的衛生部長、公共衛生當局和 KOL 進行接觸，很明顯，人們強烈需要一種安全、有效且冷藏穩定的基於蛋白質的有效替代品，以方便運輸和-現場存儲。此外，隨著我們的疫苗劑量在全球範圍內接受，我們相信消費者的選擇將在推動需求方面發揮越來越重要的作用。

Through Nuvaxovid's reassuring tolerability and safety profile, we are confident that utilization of bar vaccine can support preferences over time, building additional demand now and into the future.

通過 Nuvaxovid 令人放心的耐受性和安全性，我們相信棒狀疫苗的使用可以隨著時間的推移支持偏好，在現在和未來建立額外的需求。

Please turn to Slide 6. As we execute on the commercial rollout of Nuvaxovid, we have readied our global manufacturing infrastructure with sites around the world consistently producing vaccine at commercial scale. Through our partnership with Serum Institute as well as our Novavax-owned facilities and other manufacturing partnerships, we have significant bioreactor capacity for antigen production and achieved large-scale production of our Matrix-M adjuvant, together supporting our over 2 billion doses of annual capacity.

請轉到幻燈片 6。在我們執行 Nuvaxovid 的商業推廣時，我們已經準備好我們的全球製造基礎設施，在世界各地的工廠持續以商業規模生產疫苗。通過與 Serum Institute 以及 Novavax 擁有的設施和其他製造合作夥伴關係，我們擁有強大的抗原生產生物反應器能力，並實現了 Matrix-M 佐劑的大規模生產，共同支持我們超過 20 億劑的年產能.

Now please turn to Slide 9 -- please turn to Slide 7. In evaluating the global market demand for Nuvaxovid, data today demonstrates continued need for primary vaccination, boosters and for the pediatric market. There is still a need to increase vaccination rates globally. In fact, data from the CDC show a persistent increase in the mortality rate for the unvaccinated over recent months reiterating the urgent need to deliver our vaccine globally. These data show that mortality rates are lower for those that receive a booster dose.

現在請轉到幻燈片 9 - 請轉到幻燈片 7。在評估 Nuvaxovid 的全球市場需求時，今天的數據表明對初級疫苗接種、加強劑和兒科市場的持續需求。仍然需要在全球範圍內提高疫苗接種率。事實上，來自 CDC 的數據顯示，近幾個月來未接種疫苗者的死亡率持續上升，這再次表明我們迫切需要在全球範圍內提供疫苗。這些數據表明，接受加強劑量的人的死亡率較低。

Also, boosting is necessary to increase protection versus those that have only received the primary series, especially as variants of COVID-19 continue to emerge. We believe this presents an additional opportunity for Nuvaxovid to support the fight against the ongoing pandemic.

此外，與僅接受主要係列的保護相比，加強保護是必要的，尤其是隨著 COVID-19 變體的不斷出現。我們相信這為 Nuvaxovid 提供了一個額外的機會來支持抗擊當前的流行病。

Please turn to Slide 8, where we provide an overview of the market opportunity across primary, booster and pediatric indications as well as global opportunities to ensure equitable access to vaccine. For primary vaccination, we believe that Nuvaxovid can serve as a desirable alternative for those that remain hesitant and those that want additional vaccine options.

請轉到幻燈片 8，我們在其中概述了初級、加強和兒科適應症的市場機會，以及確保公平獲得疫苗的全球機會。對於初級疫苗接種，我們相信 Nuvaxovid 可以作為那些猶豫不決和想要額外疫苗選擇的人的理想替代品。

We also expect that waning immunity and the continued emergence of variant strains will drive ongoing demand for booster and annual revaccination and we believe our vaccine is ideally positioned to support this need through its demonstrated ability to produce robust immune responses against variants.

我們還預計，免疫力減弱和變異毒株的持續出現將推動對加強免疫和每年重新接種的持續需求，我們相信我們的疫苗能夠通過其對變異產生強大的免疫反應的能力來滿足這一需求。

In the pediatric populations, we see continued need for a differentiated vaccine option. We are encouraged by the positive results from our pediatric expansion in our PREVENT-19 Phase III trial announced earlier this month, which demonstrated our vaccine's vast potential to serve as an alternative for pediatric populations.

在兒科人群中，我們看到對差異化疫苗選擇的持續需求。我們對本月早些時候宣布的 PREVENT-19 III 期試驗中兒科擴張的積極結果感到鼓舞，這證明了我們的疫苗作為兒科人群替代品的巨大潛力。

And finally, on a global scale, we see significant gaps in vaccine access, which we believe Nuvaxovid can address through its favorable distribution and storage profile.

最後，在全球範圍內，我們看到在疫苗獲取方面存在巨大差距，我們相信 Nuvaxovid 可以通過其有利的分銷和儲存狀況來解決這一問題。

With that, I'd like to hand it over to Filip to discuss our clinical development plan and additional detail and recent clinical data for Nuvaxovid. Filip?

有了這個，我想把它交給 Filip 來討論我們的臨床開發計劃以及 Nuvaxovid 的更多細節和最近的臨床數據。菲利普?

Thank you, John. Please turn to Slide 9.

謝謝你，約翰。請轉到幻燈片 9。

John outlined the 3 major areas where we see an opportunity for a vaccine to have an additional impact. We're gathering clinical data to support both label expansion as well as policy recommendations.

John 概述了我們認為疫苗有可能產生額外影響的 3 個主要領域。我們正在收集臨床數據以支持標籤擴展和政策建議。

Let's go to Slide 10 and talk about primary vaccination. As John described, we continue to seek emergencies authorization in additional territories for primary vaccination. In parallel, we are reading data from our Phase III studies to pursue full approvals. We expect to file our BLA in the second half of this year. We're also gathering additional data for our vaccine can be used to -- for additional populations and in a more flexible manner, to allow for better use.

讓我們轉到幻燈片 10 並討論初級疫苗接種。正如約翰所描述的，我們繼續在其他地區尋求緊急情況授權以進行初級疫苗接種。與此同時，我們正在閱讀我們的 III 期研究數據以尋求全面批准。我們預計在今年下半年提交我們的 BLA。我們還在為我們的疫苗收集更多數據，這些數據可用於更多人群，以更靈活的方式，以便更好地使用。

Today, I will give a couple of examples. One from our BLA data set from our U.K. Phase III study and another study we recently launched in South Africa.

今天，我將舉幾個例子。一項來自我們英國 III 期研究的 BLA 數據集和我們最近在南非啟動的另一項研究。

Please turn to Slide 11. Here's the design of the U.S. Phase III study -- the U.K. Phase III study. In all 15,000 participants have received vaccine and have received placebo. The primary endpoint was PCR-confirmed mild, moderate or severe disease beginning 7 days after the second dose.

請轉到幻燈片 11。這是美國 III 期研究的設計——英國 III 期研究。共有 15,000 名參與者接種了疫苗並接受了安慰劑。主要終點是第二次給藥後 7 天開始的 PCR 確認的輕度、中度或重度疾病。

Please turn to Slide 12. This slide describes the emergence of variants during the conduct of the study. The cases for the primary efficacy valuation were collected over 3 months during a time window from the 10th of November to the 24th of January, as marked in the green box. You can see that the majority of patients were caused by the alpha variant, which emerged during the conduct of the study.

請轉到幻燈片 12。這張幻燈片描述了在研究進行期間出現的變體。主要療效評估的案例是在 11 月 10 日至 1 月 24 日的時間窗口內收集了 3 個月的時間，如綠色框所示。您可以看到大多數患者是由研究進行期間出現的 alpha 變體引起的。

Now let's go to Slide 13. Here we see the primary efficacy data that was used to obtain approval for emergency use authorization. The data was collected over that 3-month period, which represents a median of 55 days surveillance. There were 10 cases in the vaccine group, 96 cases in the placebo group with the resultant efficacy of approximately 90%. All the severe cases occurred in the placebo group were due to low case count, this was not specifically significant.

現在讓我們轉到幻燈片 13。這裡我們看到了用於獲得緊急使用授權批准的主要功效數據。這些數據是在這 3 個月期間收集的，這代表了 55 天監測的中位數。疫苗組10例，安慰劑組96例，總有效率約為90%。安慰劑組發生的所有重症病例都是由於病例數少，這並不特別顯著。

So let's move on to Slide 14. The data I will present today represent the BLA MAA data, the efficacy endpoints were collected over a 6-month time period and marked and in the green box on the slide. The alpha variant continues to be the predominant variant during the efficacy collection window.

所以讓我們繼續看幻燈片 14。我今天將展示的數據代表 BLA MAA 數據，功效終點是在 6 個月的時間段內收集的，並在幻燈片上的綠色框中標記和標記。在功效收集窗口期間，α 變體仍然是主要的變體。

Now let's go to Slide 15 and look at some data. Here, we have displayed high-level safety data. The safety profile is very consistent with previous studies. The event rates are low and balance between vaccine and placebo group, serious, severe and adverse event, the special interest occurred at very low frequencies.

現在讓我們轉到幻燈片 15 並查看一些數據。在這裡，我們展示了高級別的安全數據。安全性與之前的研究非常一致。疫苗組和安慰劑組之間的事件發生率低且平衡，嚴重、嚴重和不良事件，特別關注的發生頻率非常低。

Let's move to Slide 16. Here we have the placebo-controlled efficacy data collected over the 6-month surveillance period, which represents a median of approximately 100 days of surveillance. There were 24 cases in the vaccine group and 134 cases in placebo group, which yielded a vaccine efficacy of 82.7% with lower boom greater than 73%. This is consistent with the reno about the decay of antibody for this vaccine and for all other Covid vaccines. Importantly, this expanded data set, we had an adequate number of cases to statistically demonstrate vaccine efficacy against severe disease. We saw a vaccine efficacy of 100% with a lower bound confidence interval above 0.

讓我們轉到幻燈片 16。這裡我們收集了 6 個月監測期間的安慰劑對照療效數據，這代表了大約 100 天監測的中位數。疫苗組24例，安慰劑組134例，疫苗有效率為82.7%，低潮率大於73%。這與雷諾關於該疫苗和所有其他 Covid 疫苗的抗體衰減的觀點一致。重要的是，通過這個擴展的數據集，我們有足夠數量的病例來統計證明疫苗對嚴重疾病的功效。我們看到了 100% 的疫苗效力，下限置信區間高於 0。

Now let's turn to Slide 17. So this is a graphic representation of the protection. The vaccine group is in blue, while the placebo group is in gray. The vaccine group and placebo group diverged on day 0, which was the day of the second dose of vaccine was administered, indicating that efficacy can be observed early in the primary vaccination schedule.

現在讓我們轉到幻燈片 17。這是保護的圖形表示。疫苗組為藍色，而安慰劑組為灰色。疫苗組和安慰劑組在第 0 天（即接種第二劑疫苗的當天）出現分歧，這表明可以在初次接種計劃的早期觀察到療效。

Now let's go to Slide 18. The data on this slide represents our first evaluation of protection against infection. Infection is designed and defined as either still converting to the N protein or being PCR positive, thus capturing both symptomatic and asymptomatic cases. This analysis included a collected through the extended data set.

現在讓我們轉到幻燈片 18。這張幻燈片上的數據代表了我們對預防感染的第一次評估。感染被設計和定義為仍轉化為 N 蛋白或 PCR 陽性，從而捕獲有症狀和無症狀病例。該分析包括通過擴展數據集收集的。

Overall, there were 36 cases in the vaccine group and 195 cases in the placebo group, which yielded a vaccine efficacy of 82.5% with a tight lower bound of 75%.

總體而言，疫苗組有 36 例，安慰劑組有 195 例，疫苗效力為 82.5%，緊縮下限為 75%。

Okay, let's jump to Slide 19 for a quick summary. I presented data from the extended data cut that will be used to support the BLA MAA or from our U.K. Phase III study. The top line safety continues to be reassuring, clinical efficacy was maintained with the expected diminution as immune responses waned, vaccine efficacy against severe disease was preserved with no severe cases throughout the expanded period. The vaccine demonstrated protection from infection which recapitulates what we saw in our nonhuman primate studies. And this has potential implications for transmission as well as for promotion of long-term COVID sequalae. If you're not infected, you can't transmit the virus, nor can you have long COVID.

好的，讓我們跳到幻燈片 19 進行快速總結。我展示了來自擴展數據切割的數據，這些數據將用於支持 BLA MAA 或來自我們的英國 III 期研究。一線安全性繼續令人放心，隨著免疫反應的減弱，臨床療效保持在預期的下降範圍內，針對嚴重疾病的疫苗效力得以保持，在整個擴展期間沒有嚴重病例。該疫苗顯示出對感染的保護作用，這概括了我們在非人類靈長類動物研究中看到的情況。這對傳播以及促進長期 COVID 後遺症具有潛在的影響。如果你沒有被感染，你就不能傳播病毒，也不能長期感染新冠病毒。

Okay, let's turn to Slide 20 and talk about the study we began last week. In this study, we're evaluating alternate dosing schedules. -- in people living with HIV, we're evaluating both a 3-dose schedule and an extended dosing schedule to define the best approach for vaccinating immunocompromised participants.

好的，讓我們轉到幻燈片 20，談談我們上週開始的研究。在這項研究中，我們正在評估替代給藥方案。 - 在艾滋病毒感染者中，我們正在評估 3 劑計劃和延長的給藥計劃，以確定為免疫功能低下的參與者接種疫苗的最佳方法。

Additionally, we're comparing our Day 0 and 21-day schedule to 0 and 70-day schedule to generate data that will support additional flexibility in our vaccine is used in the real world. This study began last Friday and is an example of the approach we are taking to expand the reach of our primary vaccination populations.

此外，我們將第 0 天和第 21 天的時間表與第 0 天和第 70 天的時間表進行比較，以生成數據，以支持我們在現實世界中使用疫苗時具有更大的靈活性。這項研究於上週五開始，是我們為擴大初級疫苗接種人群範圍而採取的方法的一個例子。

Okay, please turn to Slide 21, and we'll talk briefly about boosting. For heterologous boosting, we are encouraged by the policy recommendations in some countries, allowing heterologous vaccination and boosting. We continue to collaborate with academic and government groups to gather additional data, and this will be used to -- and we will initiate our own studies in the second quarter.

好的，請轉到第 21 張幻燈片，我們將簡要討論提升。對於異種加強免疫，我們對一些國家的政策建議感到鼓舞，允許進行異種免疫接種和加強免疫。我們將繼續與學術和政府團體合作以收集更多數據，這將用於——我們將在第二季度開始我們自己的研究。

For homologous boosting, our initial data and regulatory filings will leverage the USC Australia Phase II study as well as data from the South Africa Phase II study. I will detail some of that data in the next slide. We anticipate this will be ready for regulatory submission in the second quarter. Additional data will be coming from our Phase III study, where we boosted all the participants. And as John mentioned, we have received support from the U.S. government to expand the adolescent study to include boosting.

對於同源促進，我們的初始數據和監管文件將利用南加州大學澳大利亞 II 期研究以及南非 II 期研究的數據。我將在下一張幻燈片中詳細介紹其中的一些數據。我們預計這將在第二季度為監管提交做好準備。額外的數據將來自我們的第三階段研究，我們提升了所有參與者。正如約翰所提到的，我們得到了美國政府的支持，以擴大青少年研究以包括增強。

Now let’s go to Slide 22 and review some of the data that will support the initial boosting indication. This is indicative data from our U.S. and Australia Phase II study. The first 2 bars displayed the wild-type neutralization response after 2 doses in the U.K. and U.S., Mexico Phase III study. Above the bars are the high levels of efficacy seen against strains closest to the original strain as well as variants. As a reminder, the majority of cases in both studies were determined to be variants.

現在讓我們轉到幻燈片 22 並查看一些支持初始增強指示的數據。這是來自我們美國和澳大利亞 II 期研究的指示性數據。在英國和美國、墨西哥 III 期研究中，前 2 個條形圖顯示了 2 劑後的野生型中和反應。條形上方是針對最接近原始菌株的菌株以及變體所看到的高水平功效。提醒一下，兩項研究中的大多數病例都被確定為變異。

On the third bar is immune response we saw after a single boosting dose of 6 months. You can see that we induced neutralizing responses were 4.5 fold higher than associated with protection in the Phase III studies giving us reason to believe we could have comparable or higher efficacy after a boosting dose.

第三條是我們在單次加強劑量 6 個月後看到的免疫反應。您可以看到，在 III 期研究中，我們誘導的中和反應比與保護相關的反應高 4.5 倍，這使我們有理由相信在加強劑量後我們可以具有相當或更高的功效。

Now please turn to Slide 23. The quality of the immune responses is equally important as the magnitude of immune response. This slide displays neutralizing response against prototype, Delta and Omicron variants. This is a stringent assay conducted at the Matt Frieman Lab in the University of Maryland, which measures 99% utilization.

現在請轉到幻燈片 23。免疫反應的質量與免疫反應的大小同樣重要。這張幻燈片顯示了對原型、Delta 和 Omicron 變體的中和反應。這是在馬里蘭大學馬特弗里曼實驗室進行的一項嚴格檢測，可測量 99% 的利用率。

On the left-hand side are the results after 2 doses, neutralizing immune responses that were preserved against all variants. There's a fourfold decrease between the original strain and the Omicron variant. On the right-hand side, you can see that after a single boost, there was a large increase neutralizing titers against all variants. The absolute levels after boosting compared favorably with those seen at their 2 doses. I want to remind you that in our Phase III study, we saw 96% to 100% protection against a prototype after 2 doses, shown here in black on the left-hand side and 82% against Delta displayed in blue on the left hand side.

左側是 2 劑後的結果，中和了針對所有變體保留的免疫反應。原始菌株和 Omicron 變體之間減少了四倍。在右側，您可以看到在單次增強後，針對所有變體的中和滴度均大幅增加。加強後的絕對水平與在 2 次劑量時看到的水平相比是有利的。我想提醒您，在我們的 III 期研究中，我們看到 2 劑後對原型的保護率為 96% 至 100%，左側以黑色顯示，左側以藍色顯示 82% 對抗 Delta .

Okay. Please turn to Slide 24, and let's talk about children. We have concluded the study in children of 12 to 18 years of age and plan to submit this to our global regulators in the first quarter. In fact, we have already submitted the clinical study report to the regulatory agencies that have mechanisms to accept submission of clinical data in advance of the complete filing. As we have previously detailed, we plan to initiate an age de-escalation study in the second quarter. But let me review a bit of data from our adolescent study to show you why we're so excited about the pediatric indication.

好的。請轉到幻燈片 24，讓我們談談孩子。我們已經完成了對 12 至 18 歲兒童的研究，併計劃在第一季度將其提交給我們的全球監管機構。事實上，我們已經將臨床研究報告提交給有機制在完成備案之前接受臨床數據提交的監管機構。正如我們之前詳述的那樣，我們計劃在第二季度啟動年齡降級研究。但讓我回顧一下我們青少年研究的一些數據，向您展示為什麼我們對兒科適應症如此興奮。

Please turn to Slide 25. This slide reviews our adolescent data. Importantly, we achieved our primary effectiveness endpoint, which showed immune responses in 12 to 18 year olds were non-inferior to low set and young adults in the main part of the Phase III study. In fact, those responses were 1.5 fold higher than seen in adults. From a regulatory perspective, by achieving this endpoint the efficacy in the adult portion of the study is deemed to apply to the adolescent. Additionally, although the number of cases was modest, we saw 82% efficacy against the Delta variant.

請轉到幻燈片 25。這張幻燈片回顧了我們的青少年數據。重要的是，我們實現了我們的主要有效性終點，在 III 期研究的主要部分中，12 至 18 歲的免疫反應不劣於低組和年輕人。事實上，這些反應比成人高出 1.5 倍。從監管的角度來看，通過達到這一終點，研究成人部分的療效被認為適用於青少年。此外，儘管病例數量不多，但我們看到 Delta 變體的療效為 82%。

Now let's move to Slide 26. Displayed here is the local reactogenicity comparing 12- to 18-year olds to 18- to 25-year olds, overall, the adolescent compared favorably to young adults. There was a small increase in mild swelling and redness seen after dose 2 likely because of the growth of teenage one. All the events were short-lived with a median duration of 1 to 2 days.

現在讓我們轉到幻燈片 26。這裡顯示的是 12 至 18 歲與 18 至 25 歲之間的局部反應原性，總體而言，青少年優於年輕人。第 2 劑後輕度腫脹和發紅有小幅增加，可能是因為青少年的生長。所有事件都是短暫的，中位持續時間為 1 至 2 天。

Now let's turn to Slide 27 and look at the solicit symptoms. The solicited reactogenicity was also favorable and compared well between adolescents to those in the young adults. There's a small increase in Grade 3 fatigue in teams, however, overall, the rates of all grades of fatigues were lower than in the young adults. All events are short-lived, median duration of 1 day except for muscle pain, which was 2 days.

現在讓我們轉到幻燈片 27 並查看徵集症狀。請求的反應原性也很有利，並且在青少年與年輕人之間進行了很好的比較。團隊中 3 級疲勞的發生率略有增加，但總體而言，所有級別的疲勞發生率均低於年輕人。所有事件都是短暫的，中位持續時間為 1 天，除了肌肉疼痛為 2 天。

The reason we're so excited about this data is because the reactogenicity appears favorable compared to the young adults despite the immune response being significantly higher than seen in the younger adults. This may bode well for vaccine evaluation in young children and may help increase vaccine acceptability in this age group.

我們對這一數據如此興奮的原因是，儘管免疫反應明顯高於年輕人，但與年輕人相比，反應原性似乎更好。這對於幼兒的疫苗評估可能是個好兆頭，並可能有助於提高該年齡組對疫苗的接受度。

Finally, let's go to Slide 28 and look at our near-term pipeline. Displayed here is our near-term pipeline, and I want to point out some of the clinical highlights. As we've talked about from Nuvaxovid, we will continue to work on our label and policy expansions, including boosting and pediatric indications.

最後，讓我們轉到幻燈片 28，看看我們的近期管道。這裡展示的是我們的近期管道，我想指出一些臨床亮點。正如我們從 Nuvaxovid 談到的，我們將繼續致力於我們的標籤和政策擴展，包括促進和兒科適應症。

For the Omicron vaccine, we have previously stated we have 1 in development. It still isn't clear if an Omicron vaccine is needed. I've share data that our vaccine has worked well against all variants in the U.S. and U.K. Phase III studies, and our immune responses against Omicron appears sound, especially after boosting dose. However, we are in the midst of a GMP campaign at the manufacture the vaccine, and the material will be available towards the end of the first quarter. Our plan is to conduct a strain change study immediately thereafter.

對於 Omicron 疫苗，我們之前曾表示我們有 1 種正在開發中。目前尚不清楚是否需要 Omicron 疫苗。我分享的數據表明，我們的疫苗在美國和英國的 III 期研究中對所有變體都有效，而且我們對 Omicron 的免疫反應似乎很好，尤其是在加強劑量後。但是，我們在疫苗生產過程中正在進行 GMP 活動，材料將在第一季度末提供。我們的計劃是此後立即進行應變變化研究。

In these sorts of studies, we being licensure by comparing the immune response induced by the Omicron vaccine with immune responses induced by the original strain, which is similar to what's done for influenza when the strains change on an annual basis. As far as our combination influenza-COVID study goes, it's complete and being analyzed.

在這些類型的研究中，我們通過比較 Omicron 疫苗誘導的免疫反應與原始毒株誘導的免疫反應來獲得許可，這類似於當毒株每年發生變化時對流感所做的事情。就我們的流感-COVID 聯合研究而言，它已經完成並正在分析中。

As you remember, the study explored a wide range of antigen doses for the combination vaccine as well as for the quadrivalent influenza vaccine by itself. We expect the results to be available in April. And based on those results, we will conduct the Phase II studies to confirm specific formulations that we will take into the pivotal study.

如您所知，該研究探索了聯合疫苗以及四價流感疫苗本身的多種抗原劑量。我們預計結果將在 4 月公佈。基於這些結果，我們將進行 II 期研究，以確認我們將納入關鍵研究的特定配方。

Okay. Let me turn it over to Jim to discuss our financial results.

好的。讓我把它交給吉姆討論我們的財務結果。

Thank you, Filip. Please turn to Slide 29. This afternoon, we announced our financial results for the fourth quarter and full year 2021. I'll begin with an overview of the full year 2021 total revenue performance and our year-end cash position and then my commentary will focus primarily on our fourth quarter results.

謝謝你，菲利普。請轉到幻燈片 29。今天下午，我們宣布了 2021 年第四季度和全年的財務業績。我將首先概述 2021 年全年的總收入表現和我們的年終現金狀況，然後我的評論將主要關注我們的第四季度業績。

For the full year 2021, Novavax recorded total revenue of $1.1 billion, a milestone for the company. This $1.1 billion reflects 141% growth in total revenue year-over-year and consists of $949 million of grants revenue and $198 million of royalty and other revenue. Grants revenue has been an important source of capital to fund our Nuvaxovid clinical program and scale up of our commercial manufacturing capabilities. During 2021, we recorded grants revenue of $811 million and $135 million from the U.S. government and CEPI, respectively. Under the U.S. government agreements, we have $800 million of funding remaining, and we expect to recognize the majority of this amount during 2022. For 2022, we do not expect to recognize a material amount of grant revenue from CEPI as we've completed the activities funded under this agreement.

2021 年全年，Novavax 的總收入為 11 億美元，這對公司來說是一個里程碑。這 11 億美元反映了總收入同比增長 141%，其中包括 9.49 億美元的贈款收入和 1.98 億美元的特許權使用費和其他收入。贈款收入一直是資助我們的 Nuvaxovid 臨床計劃和擴大我們的商業製造能力的重要資金來源。 2021 年，我們分別從美國政府和 CEPI 獲得了 8.11 億美元和 1.35 億美元的贈款收入。根據美國政府協議，我們還有 8 億美元的資金剩餘，我們預計將在 2022 年確認大部分資金。對於 2022 年，我們預計不會從 CEPI 確認大量贈款收入，因為我們已經完成了根據本協議資助的活動。

We ended 2021 with $1.5 billion in cash and received an additional $350 million milestone payment from Gavi in the first quarter of 2022. This means Novavax is well capitalized as we launch Nuvaxovid globally.

我們以 15 億美元的現金結束了 2021 年，並在 2022 年第一季度從 Gavi 收到了額外的 3.5 億美元里程碑付款。這意味著隨著我們在全球推出 Nuvaxovid，Novavax 資本充足。

Please turn to Slide 30. Turning to our fourth quarter 2021 results. Novavax recorded total revenue of $222 million compared to $280 million in the fourth quarter of 2020. Fourth quarter 2021 royalties and other revenue grew to $127 million compared to $20 million in the prior year and reflect the additional royalties from our license partners on their sales to South Korea and Indonesia.

請轉到幻燈片 30。轉到我們 2021 年第四季度的業績。 Novavax 的總收入為 2.22 億美元，而 2020 年第四季度為 2.8 億美元。 2021 年第四季度的特許權使用費和其他收入增長至 1.27 億美元，而去年同期為 2000 萬美元，這反映了我們的許可合作夥伴向其銷售的額外特許權使用費韓國和印度尼西亞。

Fourth quarter 2021 grants revenue of $95 million compares to $259 million in the prior year. The decline in grants revenue resulted from the completion of the manufacturing scale-up activity funded by CEPI earlier in 2021.

2021 年第四季度的贈款收入為 9500 萬美元，而去年同期為 2.59 億美元。贈款收入的下降是由於 CEPI 於 2021 年早些時候完成了由 CEPI 資助的製造規模擴大活動。

We recorded total operating expenses of $1 billion in the fourth quarter of 2021, including $963 million for R&D. This reflects a significant increase to R&D expenses as compared to both the same quarter prior year and the third quarter of 2021. This increase was primarily the result of the accelerated recognition of embedded lease expenses tied to our contract manufacturing agreements, and the expensing of Nuvaxovid prelaunch inventory that in the future will be capitalized to the balance sheet. Neither of these items impact cash flow in the period and by expensing these manufacturing costs in 2021, we expect lower cost of goods sold expense in future periods. We will revisit the concept of less-than-full cost COGS on our first quarter call.

我們在 2021 年第四季度記錄了 10 億美元的總運營費用，其中包括 9.63 億美元的研發費用。這反映了與去年同期和 2021 年第三季度相比，研發費用顯著增加。這一增加主要是由於加速確認與我們的合同製造協議相關的嵌入式租賃費用，以及 Nuvaxovid 的費用未來將在資產負債表中資本化的預發行庫存。這些項目都不會影響該期間的現金流，並且通過在 2021 年將這些製造成本費用化，我們預計未來期間的商品銷售成本成本會降低。我們將在第一季度電話會議上重新審視低於全成本 COGS 的概念。

When seeking to understand the operational run rate for R&D costs during 2021, we believe our Q1 to Q3 R&D expense run rate is a better starting point for estimating future R&D cost trends. We expect our full year 2022 R&D expenses to be lower than 2021, and a significant portion of 2022 R&D costs will continue to be funded by the U.S. government.

在尋求了解 2021 年研發成本的運營運行率時，我們認為第一季度至第三季度的研發費用運行率是估計未來研發成本趨勢的更好起點。我們預計 2022 年全年研發費用將低於 2021 年，並且 2022 年研發費用的很大一部分將繼續由美國政府資助。

We recorded general and administrative expenses of $84 million in the fourth quarter of 2021 as compared to $61 million in the fourth quarter of 2020. This increased the G&A as the result of our support of the Nuvaxovid launch, and we expect G&A to continue to grow into 2022 as we further enhance our commercial capabilities to bring Nuvaxovid to markets around the world. And finally, for the fourth quarter of 2021, we recorded a net loss of $846 million as compared to a net loss of $178 million in the fourth quarter of 2020.

我們在 2021 年第四季度記錄了 8400 萬美元的一般和管理費用，而 2020 年第四季度為 6100 萬美元。由於我們支持 Nuvaxovid 的推出，這增加了 G&A，我們預計 G&A 將繼續增長到 2022 年，我們將進一步增強我們的商業能力，將 Nuvaxovid 推向世界各地的市場。最後，在 2021 年第四季度，我們錄得 8.46 億美元的淨虧損，而 2020 年第四季度的淨虧損為 1.78 億美元。

Please turn to Slide 31, where we'll provide an overview of our financial guidance for 2022. As discussed earlier, we expect to achieve full year 2022 total revenue of between $4 billion and $5 billion. As a reminder, total revenue reflects all sources, including product sales in Nuvaxovid by Novavax, grants revenue, royalties and other revenue. We look forward to sharing our progress towards realizing this total revenue guidance and plan to provide additional guidance related to full year 2022 operating expenses on future earnings calls.

請轉到幻燈片 31，我們將在其中概述我們對 2022 年的財務指導。如前所述，我們預計 2022 年全年總收入將在 40 億美元至 50 億美元之間。提醒一下，總收入反映了所有來源，包括 Novavax 在 Nuvaxovid 的產品銷售、贈款收入、特許權使用費和其他收入。我們期待分享我們在實現這一總收入指導方面取得的進展，併計劃在未來的收益電話會議上提供與 2022 年全年運營費用相關的額外指導。

With that, I'd like to turn it over to Stan to discuss our upcoming strategic priorities.

有了這個，我想把它交給斯坦來討論我們即將到來的戰略重點。

Thanks, Jim. We're pleased to report those results of a highly productive fourth quarter, reflecting our rapid transition into a global commercial organization. With significant results achieved to date and our expectation of achieving $4 billion to $5 billion of total revenue in this year alone, I'd like to end today's call by providing an overview of our strategic areas of focus for the remainder of '22.

謝謝，吉姆。我們很高興地報告第四季度的高產業績，反映了我們向全球商業組織的快速過渡。迄今為止取得的顯著成果以及我們預計僅在今年就實現 40 億至 50 億美元的總收入，我想通過概述我們在 22 年剩餘時間的戰略重點領域來結束今天的電話會議。

On the commercial front, through '22, we will distribute doses globally to our customers to meet our revenue targets. On the regulatory and manufacturing front, we expect to gain additional authorizations where we have already filed, including in the U.S. We will pursue full approval of our vaccine, including filing our BLA in the second half of '22. We'll add additional manufacturing sites to our filings and will manufacture doses to supply all of our current as well as additional demand for 2022. And finally, we will develop -- we will advance clinical development of other vaccine candidates in our pipeline, including continuing clinical development to expand the use of Nuvaxovid into additional indications such as boosters and into the pediatric population as well as continuing the development of our Omicron vaccine and will advance our COVID influenza combination vaccine, which is a key component of our pipeline. We expect to announce data in April and to initiate a Phase II trial that will also include a NanoFlu stand-alone arm, bring us one step closer to pursuing licensure of our product.

在商業方面，到 22 年，我們將在全球範圍內向我們的客戶分髮劑量，以實現我們的收入目標。在監管和製造方面，我們希望在我們已經提交的地方獲得額外的授權，包括在美國。我們將尋求對我們的疫苗進行全面批准，包括在 22 年下半年提交我們的 BLA。我們將在我們的備案文件中增加額外的生產基地，並將生產劑量以滿足我們目前以及 2022 年的所有額外需求。最後，我們將開發——我們將推進我們管道中其他候選疫苗的臨床開發，包括繼續臨床開發，將 Nuvaxovid 的使用擴大到其他適應症，如加強劑和兒科人群，並繼續開發我們的 Omicron 疫苗，並將推進我們的 COVID 流感聯合疫苗，這是我們管道的關鍵組成部分。我們預計將在 4 月公佈數據，並啟動一項 II 期試驗，該試驗還將包括一個 NanoFlu 獨立臂，使我們離獲得我們的產品許可更近了一步。

Thanks for your attention. I will now turn it over to the operator for Q&A.

感謝您的關注。我現在將其交給接線員進行問答。

(Operator Instructions) Our first question today comes from Roger Song from Jefferies.

（操作員說明）我們今天的第一個問題來自 Jefferies 的 Roger Song。

Congrats for all the progress. So the first question from me is regarding the sales guidance or revenue guidance. I think that's very nice. You provided $4 billion to $5 billion overall guidance. Could you provide any comments around the breakdown between the product sales like APA or versus the royalty and grant and other revenues?

祝賀所有的進步。所以我的第一個問題是關於銷售指導或收入指導。我認為這非常好。您提供了 40 億至 50 億美元的總體指導。您能否就 APA 等產品銷售或特許權使用費、贈款和其他收入之間的細分提供任何評論？

Yes, I'll take it. This is Stan. And the vast majority is related to product sales. And of that, the vast majority of that is related to Nuvaxovid product sales. And so we book Nuvaxovid product sales as product has shifted into the hands of our customers.

是的，我會接受的。這是斯坦。而且絕大多數與產品銷售有關。其中，絕大多數與 Nuvaxovid 產品銷售有關。因此，我們預訂 Nuvaxovid 產品銷售，因為產品已轉移到我們的客戶手中。

On our partner sales such as Serum, we booked the portion of the sales that is revenue related to us through royalties. And so it's virtually all product-related sales with the exception of the government grants that Jim mentioned, would be largely expanded in 2022 and on the order of magnitude of about $600 million to $800 million, in that range.

在我們的合作夥伴銷售（如 Serum）中，我們通過版稅計入了與我們相關的收入部分。因此，除了吉姆提到的政府補助之外，幾乎所有與產品相關的銷售額都將在 2022 年大幅擴大，並在該範圍內達到約 6 億至 8 億美元的數量級。

Of the $800 million, we expect more than half will occur in 2022.

在 8 億美元中，我們預計超過一半將發生在 2022 年。

Yes. Okay. So it's product-related revenue.

是的。好的。所以這是與產品相關的收入。

Go ahead, sorry. Hello?

繼續，對不起。你好？

Next question? Yes. Sorry, did I miss something?

下一個問題？是的。抱歉，我錯過了什麼嗎？

Yes. No -- yes, that's great. And then regarding the COVID-flu combo vaccine data in April this year, so just -- can you just provide some kind of your expectation and what is the go-no-go decision point to move forward into the Phase II?

是的。不——是的，那太好了。然後關於今年 4 月的 COVID-flu 組合疫苗數據，所以只是 - 你能提供一些你的期望嗎？進入第二階段的決定點是什麼？

Yes. So we go into this trial, knowing some things already. We know how our -- the response to our flu vaccination was and including in a Phase III immunogenicity trial, we know from preclinical studies what we wanted to show was that by putting the COVID and the NanoFlu vaccine together is neither one suppressed the immune response to the other. And in animals, we found that we need to -- we need to confirm that in humans, but we're pretty confident that those data will be available to us.

是的。所以我們進入這個試驗，已經知道一些事情。我們知道我們對流感疫苗的反應如何，包括在 III 期免疫原性試驗中，我們從臨床前研究中知道，我們想要證明的是，將 COVID 和 NanoFlu 疫苗放在一起並不會抑制免疫反應給對方。在動物身上，我們發現我們需要——我們需要在人類身上證實這一點，但我們非常有信心這些數據可供我們使用。

And then we took a pretty broad range of vaccine arms, so that we could come to a conclusion on what dose level we want between flu and COVID in various arms. And that will be really key because it's a more complicated vaccine. And there, we want to make sure we've got the right dose. So that's the point of the Phase I/II trial. I think it will give us information to go into a Phase II trial that will confirm the dose selection, and that will be later this year.

然後我們採用了相當廣泛的疫苗組，這樣我們就可以得出結論，我們希望在不同的組中流感和 COVID 之間的劑量水平。這將非常關鍵，因為它是一種更複雜的疫苗。在那裡，我們要確保我們有正確的劑量。這就是 I/II 期試驗的重點。我認為它將為我們提供進入 II 期試驗的信息，該試驗將確認劑量選擇，這將在今年晚些時候進行。

Great. Maybe just one last one from me is the, recently your competitor Sanofi and GSK, they provide some positive data for their protein-based vaccine. And maybe just curious your thoughts around how this will impact your commercial adoption for [all that] vaccine?

偉大的。也許我的最後一個是，最近你的競爭對手賽諾菲和葛蘭素史克，他們為他們的蛋白質疫苗提供了一些積極的數據。也許只是好奇您對這將如何影響您對 [all that] 疫苗的商業採用的想法？

Yes. I don't think it has much impact on us right now. I mean it's hard for us to tell about a competitive product when we haven't seen the data, and we don't know the timing of when they're going to file or enter into the marketplace. So we're pretty confident based upon what little we've seen that our combination of efficacy data and safety data and the fact that we're in the market will give us a good head start on any potential competition.

是的。我認為它現在對我們沒有太大影響。我的意思是，當我們沒有看到數據時，我們很難判斷一個有競爭力的產品，而且我們不知道他們何時提交或進入市場的時間。因此，我們非常有信心，基於我們所見的很少，我們的功效數據和安全性數據的組合以及我們在市場上的事實將使我們在任何潛在的競爭中取得良好的開端。

Our next question comes from Charles Duncan from Cantor Fitzgerald.

我們的下一個問題來自 Cantor Fitzgerald 的 Charles Duncan。

Stan and team, congrats on executing well during a challenging environment throughout '21. Also, thanks for the sales guidance. I did want to ask you a little bit more detail about that. In terms of -- you said that it was primarily driven by actual sales of Nuvaxovid, could you give us some color on the timing? Is this a quarterly build? Or would you anticipate bulk of the sales in the first half of this year and then it to be relatively stable over the course of the year?

Stan 和他的團隊，恭喜你在 21 世紀充滿挑戰的環境中表現出色。另外，感謝銷售指導。我確實想問你更多關於這方面的細節。就 - 你說它主要是由 Nuvaxovid 的實際銷售推動的，你能給我們一些時間上的顏色嗎？這是一個季度構建嗎？或者你會預計今年上半年的大部分銷售額，然後在一年中相對穩定？

Well, we're not -- I'm sorry, Charles, but we're not giving quarterly guidance. And so we've come up with -- we've got these APAs that are in place. We have manufacturing schedules, which will support them. And it's the timing of our customers and when they want their shipments will determine the quarterly pace of these. And of course, there's going to be a fairly quick out the door because we've already announced that we've shipped 27 million doses to Europe. And jammed, I note that we've shipped 27 million doses to Europe in January and so for further distribution to our customers.

好吧，我們不是 - 對不起，查爾斯，但我們沒有提供季度指導。所以我們想出了——我們已經有了這些APA。我們有製造計劃，這將為他們提供支持。這是我們客戶的時間安排，他們何時需要他們的出貨量將決定這些產品的季度速度。當然，這將是一個相當快的出口，因為我們已經宣布我們已經向歐洲運送了 2700 萬劑疫苗。卡住了，我注意到我們已經在 1 月份向歐洲運送了 2700 萬劑疫苗，以便進一步分發給我們的客戶。

So a lot's gone out the door. We've got -- as John also noted, we have a 42 million dose order just from Europe in the second quarter. And -- but as far as further definition of doses and doses by quarter, we're not able to provide that guidance right now.

所以很多東西都出了門。我們有——正如約翰也指出的那樣，我們在第二季度從歐洲獲得了 4200 萬劑訂單。而且 - 但就劑量和按季度劑量的進一步定義而言，我們現在無法提供該指導。

Okay. That's cool. We're okay with that. Regarding the guidance, though, is it dependent on U.S. approval? It doesn't seem like it would be, but is there perhaps the $4 million versus $5 million -- or billion dependent on approval and use in the United States.

好的。這很酷。我們沒關係。但是，關於指導，它是否取決於美國的批准？似乎不會，但可能是 400 萬美元與 500 萬美元 - 或 10 億美元取決於美國的批准和使用。

I think the U.S. represents upside potential for us.

我認為美國代表著我們的上行潛力。

Okay. And then relative to the BLA, you mentioned the BLA in Europe and then potential for BLA filing here in the United States. Can you give us a little bit of color on what additional work needs to be done to support a BLA filing here in the U.S.? And are you signaling that we should forget about an emergency use authorization and really focus on BLA?

好的。然後相對於 BLA，您提到了歐洲的 BLA，然後是在美國提交 BLA 的可能性。您能否告訴我們需要做哪些額外的工作來支持在美國提交 BLA 申請？你是否在暗示我們應該忘記緊急使用授權並真正專注於 BLA？

No is the answer to the last question, but I'll let Filip step in and maybe provide some opinion on BLA.

否是最後一個問題的答案，但我會讓 Filip 介入，並可能就 BLA 提供一些意見。

Sure. I think, just to reiterate, we're going full blast for our EUA. We're in contact with the FDA periodically to make sure all the questions are answered. So looking forward to moving forward with that. And as you know, we don't control the pace they review the filing, we're looking forward to a successful of our packet in the near future.

當然。我想，重申一下，我們將為我們的 EUA 全力以赴。我們會定期與 FDA 聯繫，以確保所有問題都得到解答。所以期待著繼續前進。如您所知，我們無法控制他們審查文件的速度，我們期待在不久的將來我們的數據包取得成功。

The clinical data that's required for the BLA and the MAA are very similar. What they're really looking for is longer-term safety and it's a long-term safety of the product. The U.S. is different from some territories, including Europe, in that from time to time, they want a lot block-consistency study. So that's an additional small study we would have to conduct to support the U.S. BLA as opposed to the MAAs.

BLA 和 MAA 所需的臨床數據非常相似。他們真正在尋找的是長期的安全性，這是產品的長期安全性。美國與包括歐洲在內的一些地區不同，他們不時需要大量的塊一致性研究。因此，這是我們必須進行的一項額外的小型研究，以支持美國 BLA 而不是 MAA。

Now all that being said, a condition for us to get the MAAs are well, we had the successful EUAs first before we move on to the plan licensure. And that's the path we're going to be following in the U.S. as well.

話雖如此，我們獲得 MAA 的條件很好，在我們繼續獲得計劃許可之前，我們首先獲得了成功的 EUA。這也是我們將在美國遵循的道路。

Okay. That's super. Last quick question is on safety since you brought it up. So I guess I'm wondering if you've seen any outsized incidence of myocarditis in patients -- or in people who have then vaccinated? And does that change over time as you track them over time, any incidents?

好的。太棒了自從您提出以來，最後一個快速問題是關於安全的。所以我想我想知道你是否在患者中看到過任何心肌炎的超常發病率 - 或者在隨後接種疫苗的人中？當您隨著時間的推移跟踪它們時，這是否會隨著時間的推移而改變，任何事件？

Yes. So we, of course, take all safety very seriously. And we've previously announced that in any safety database as large as ours, you expect to see cases in the vaccine and placebo group. What I can tell you is like those rates of myocarditis or balanced between the vaccine and placebo group.

是的。因此，我們當然非常重視所有安全問題。而且我們之前已經宣布，在像我們這樣大的任何安全數據庫中，您都希望在疫苗組和安慰劑組中看到病例。我可以告訴你的是心肌炎的發病率或疫苗組和安慰劑組之間的平衡。

Additionally, you know that our safety has been adjudicated by close to a dozen regulators globally and if you scrutinize our label, you'll see that we don't have myocarditis that had a drug reaction in any of our labels. Now all that being said, as acknowledged that ours is a relatively small database, only roughly 60,000 individuals. So as we start selling millions and millions of doses, we'll get a much better ability to understand if there's any risk for myocarditis or not.

此外，您知道我們的安全性已由全球近十幾個監管機構裁定，如果您仔細查看我們的標籤，您會發現我們的任何標籤中都沒有出現藥物反應的心肌炎。現在說了這麼多，我們承認我們的數據庫是一個相對較小的數據庫，只有大約 60,000 個人。因此，當我們開始銷售數百萬劑時，我們將更好地了解是否存在心肌炎風險。

Okay. Very good. That's helpful. Congrats on the progress last year and into this year.

好的。很好。這很有幫助。祝賀去年和今年取得的進展。

Our next question comes from Georgi Yordanov from Cowen and Company.

我們的下一個問題來自 Cowen and Company 的 Georgi Yordanov。

Congratulations on all the progress for me as well. Just a clarification on the guidance. Is there an expected time line in the countries that have signed the APAs we need to accept doses by? And again, related to the $4 billion to $5 billion, do you expect the majority of the currently signed APAs to be satisfied this year?

也祝賀我取得的所有進展。只是對指導的澄清。在簽署了我們需要接受劑量的 APA 的國家/地區，是否有預期的時間表？再說一次，與 40 億至 50 億美元有關，您預計目前簽署的大多數預約定價安排今年會得到滿足嗎？

And then as a follow-up, our estimates suggest that you could generate $2 billion to $3 billion in cash flows in the next, let's say, 12 to 18 months. How do you plan to utilize this cash? What are your thoughts on potential BD opportunities or share buybacks?

然後作為後續行動，我們的估計表明，你可以在接下來的 12 到 18 個月內產生 20 億到 30 億美元的現金流。您打算如何使用這筆現金？您對潛在的 BD 機會或股票回購有何看法？

Georgi, John Trizzino here. So yes, the APAs are behind and backing up all of the expectation for our revenue guidance this year. There -- so we don't typically reveal any kind of detail timing obligations. But we're, as we've talked about in the presentation, shipping across the board to all of the APAs. And so I think the timing of all the shipments is in line and we feel real confident about what the APAs are that are supporting the revenue recognition.

喬治，約翰特里齊諾在這裡。所以，是的，APA 支持並支持我們今年對收入指導的所有預期。那裡 - 所以我們通常不會透露任何詳細的時間義務。但是，正如我們在演示文稿中談到的那樣，我們正在向所有 APA 全面運送。因此，我認為所有發貨的時間安排都是一致的，我們對支持收入確認的 APA 非常有信心。

As far as BD opportunities are concerned, I think I'll probably pass it back to Stan mostly for that, but I think it's probably an expectation that we would be utilizing our cash in an effective way. But Stan?

就 BD 機會而言，我想我可能會主要為此將其轉回給 Stan，但我認為這可能是一種期望，即我們將以有效的方式利用我們的現金。但是斯坦?

Well, thanks. Thanks For ducking that one, John. So yes, we do expect to generate cash, and the cash will be used for invested in our internal projects like the combination of NanoFlu and other respiratory parts of our franchise. Part of it will be used to explore BD opportunities. And I think that's where our focus will be -- I doubt that our focus on stock buyback in the next 12 months.

非常感謝。謝謝你避開那個，約翰。所以是的，我們確實希望產生現金，這些現金將用於投資我們的內部項目，例如 NanoFlu 和我們特許經營的其他呼吸系統部分的組合。其中一部分將用於探索 BD 機會。我認為這就是我們的重點——我懷疑我們在未來 12 個月內對股票回購的關注。

That's great. And then just a quick follow-up. Given that there could potentially be a significant booster market this fall, maybe could you just talk about how do you see yourself prepared to participate in it? Some of your competitors have indicated plans to develop bivalent boosters, is that something in the plans? And would you be able to generate data to get authorization ahead of the fall? Or given the strong data you've already generated do you believe the stand-alone vaccine will be sufficient?

那太棒了。然後只是快速跟進。鑑於今年秋天可能會有一個重要的助推器市場，也許您能談談您如何看待自己準備參與其中嗎？您的一些競爭對手已經表示計劃開發二價助推器，這是計劃中的內容嗎？您是否能夠生成數據以在秋季之前獲得授權？或者鑑於您已經生成的強大數據，您認為獨立疫苗就足夠了嗎？

Dr. Dubovsky?

杜博夫斯基博士？

Thank you. It's a good question. And we're obviously building our database both for homologous boosting, including looking at multiple rounds of boosting the Phase II in U.S. Australia that's now vaccinated people with upper 4 doses and the studies we're planning for heterologous boosting also envision at 3 or 4 doses in boosting on top of heterologous vaccination.

謝謝你。這是個好問題。而且我們顯然正在為同源加強建立我們的數據庫，包括查看美國澳大利亞的多輪加強 II 期，該階段現在已經接種了 4 劑以上的人，我們計劃進行異源加強的研究也設想在 3 或 4在異種疫苗接種的基礎上加強劑量。

So it isn't -- it really isn't clear to us if a buydown will be required. It isn't clear to us that a Omicron-specific vaccine will be required. But we're going to be prepared for both. So the initial study design calls for looking at Omicron compared to the original prototype [Wuhan]. But how we insert the bivalent product into that study or a subsequent study or alternate study, we're deciding on right now.

所以不是——我們真的不清楚是否需要買斷。我們不清楚是否需要 Omicron 特異性疫苗。但我們將為兩者做好準備。因此，最初的研究設計要求將 Omicron 與原始原型 [武漢] 進行比較。但是我們如何將二價產品插入該研究或後續研究或替代研究，我們現在正在決定。

I guess I should say you know that our dose -- our antigen level is very, very low in our vaccine. And there's not a problem for us to include alternate additional antigens. You can see that from our flu product, which the amount of range we have is much, much higher than what we have in the COVID vaccine. So it's not a specific technology limitation for us to have a polyvalent vaccine, including bivalent vaccine.

我想我應該說你知道我們的劑量——我們的疫苗中的抗原水平非常非常低。對我們來說，加入替代的額外抗原也沒有問題。您可以從我們的流感產品中看到這一點，我們擁有的範圍遠遠高於我們在 COVID 疫苗中的範圍。因此，擁有多價疫苗（包括二價疫苗）對我們來說並不是一個特定的技術限制。

Our next question comes from Mayank Mamtani from B. Riley Securities.

我們的下一個問題來自 B. Riley Securities 的 Mayank Mamtani。

Congrats on a productive quarter and year, and thanks for providing a helpful 2022 outlook. And let me also pass on, thanks for the revenue guidance there. So -- but first question, causing some confusion on the fourth quarter numbers, maybe I can ask Jim. So 2 part on revenue and cost recognition methodology here. So as you've recognized stockpile doses on P&L and maybe going forward on balance sheet, could you just clarify, do we still assume manufacturing about 2 billion doses this year? And more importantly, it would be helpful to understand the OpEx rate. I know you said 1Q to 3Q to be a better proxy, but obviously, people are interested in learning about your cash flow generation this year. So OpEx is an important part of the equation. And then I have a follow-up on revenue guidance.

祝賀一個富有成效的季度和年度，並感謝您提供有用的 2022 年展望。讓我也繼續說下去，感謝那裡的收入指導。所以——但是第一個問題，在第四季度的數字上造成了一些混亂，也許我可以問吉姆。所以這裡是關於收入和成本確認方法的 2 部分。因此，既然您已經在損益表上確認了庫存劑量，並且可能在資產負債表上繼續進行，您能否澄清一下，我們是否仍假設今年生產約 20 億劑？更重要的是，了解 OpEx 率會有所幫助。我知道你說 1Q 到 3Q 是一個更好的代理，但很明顯，人們有興趣了解你今年的現金流量。所以運營支出是等式的重要組成部分。然後我對收入指導進行了跟進。

Well, thanks for the question. And of course, certainly anticipated a great deal of interest in our -- the shape of our business as we commercialize Nuvaxovid. When providing guidance on the R&D trend, what we're sharing with you is the R&D trends whereby we are capitalizing the inventory, meaning that the vast majority of our R&D is clinical activity and then, of course, the manufacturing in support of clinical.

嗯，謝謝你的問題。當然，當我們將 Nuvaxovid 商業化時，當然預計會對我們的業務形態產生極大的興趣。在提供有關研發趨勢的指導時，我們與您分享的是我們利用庫存資本化的研發趨勢，這意味著我們的絕大多數研發是臨床活動，當然還有支持臨床的製造。

And that's very different from what you saw in the fourth quarter where there was a significant prelaunch inventory that in subsequent periods would find its way onto our balance sheet. The shape of R&D when you compare 2022 to 2021 full year is we expect 2022 to be lower. So hopefully, that alone is helpful. We will provide additional cost structure guidance beginning next quarter. And so I'm not going to be able to provide any more details on that today. I will reinforce that we have built up our manufacturing capability to produce up to 2 billion doses in the year.

這與你在第四季度看到的非常不同，第四季度有大量的預發布庫存，在隨後的時期會進入我們的資產負債表。當您將 2022 年與 2021 年全年進行比較時，研發的形狀是我們預計 2022 年會更低。所以希望，僅此一項是有幫助的。我們將從下個季度開始提供額外的成本結構指導。所以我今天不能提供更多細節。我要強調的是，我們已經建立了製造能力，可以在一年內生產多達 20 億劑。

Okay. Great Okay. And then the second question, maybe for John, in terms of the quality control process that is happening in the original country, India, where the vaccines are coming from, and then they get to the particular country, there's a local quality control process and then subsequently, there's revenue recognition. So can you clarify -- different countries have different timing and processes. Can you just clarify what would be the expectation for U.S., for instance? And then how does this all come together for a statement you put out in third quarter filing of potentially recognizing $7.2 billion in APAs at some point across these different quarters, initial quarters? .

好的。好的好的。然後是第二個問題，也許是約翰，關於在原國家印度發生的質量控製過程，疫苗來自哪裡，然後它們到達特定國家，有一個當地的質量控製過程，並且然後是收入確認。您能否澄清一下——不同的國家有不同的時間和流程。例如，您能否澄清一下對美國的期望？那麼，您在第三季度提交的一份聲明中說，在這些不同季度（初始季度）的某個時間點，可能會承認 72 億美元的 APA 的聲明，這一切是如何結合在一起的？ .

To clarify, I think what you're referencing is a disclosure around performance obligations of $7.2 billion. Is that correct?

澄清一下，我認為您所指的是有關 72 億美元履約義務的披露。那是對的嗎？

That's correct.

這是正確的。

Okay. When you see our K, it will say $8 billion, right? And it's everything from the outstanding amounts under operation work speed, our order book of APAs, milestones and adjuvant commitments from our license partners. So there's a number of different items in there. And so as you can tell, it's above our guidance range of $4 billion to $5 billion. And therefore, you'd expect that we'd meet those obligations in this year into next.

好的。當你看到我們的 K 時，它會說 80 億美元，對吧？這包括運營工作速度下的未償金額、我們的 APA 訂單、里程碑和我們的許可合作夥伴的輔助承諾。所以里面有很多不同的項目。如您所知，它高於我們 40 億至 50 億美元的指導範圍。因此，您預計我們會在今年到明年履行這些義務。

Great. And then just a quick follow-up for Fil on the NanoFlu COVID combo next study. Would that include a bivalent or a Omicron-specific construct, this study you're planning for? And then on the -- great to see the 6-month durability data, some cases in the Delta wave. Are you able to put in context what we may have seen from the currently, very effective EUA-approved vaccine at that time period, maybe in a comparable way because it looks like most of the data was in the Alpha wave?

偉大的。然後只是對 NanoFlu COVID 組合下一項研究中 Fil 的快速跟進。您計劃進行的這項研究是否包括二價或 Omicron 特定結構？然後 - 很高興看到 6 個月的耐用性數據，在 Delta 浪潮中的一些案例。您能否將我們在當時非常有效的 EUA 批准的疫苗中看到的內容放在上下文中，也許以類似的方式，因為看起來大部分數據都在 Alpha 波中？

Yes. So let me take you this separately. Right now, our plans are to not use Omicron in our combination in the Phase II study. Now some of that will depend what happens as the pandemic evolves. We'll have that vaccine in hand, and it certainly wouldn't be a problem to include the Omicron into the quadrivalent study. What we're looking for is more of a proof of concept. And by including the prototype strain in there, we can do a direct in logic comparison back to the Phase III studies that were associated with protection, both in the U.K. and the U.S.

是的。所以讓我把這個分開。目前，我們的計劃是在 II 期研究的組合中不使用 Omicron。現在，其中一些將取決於隨著大流行的發展會發生什麼。我們將擁有該疫苗，將 Omicron 納入四價研究當然不是問題。我們正在尋找的更多的是概念證明。通過在其中包含原型菌株，我們可以直接在邏輯上比較與英國和美國的保護相關的 III 期研究。

Now as far as -- I think we wanting me to speculate on what the durable protection would be like as alternate strains emerge. And as you know, we don't have any data on that other the immunogenicity data I shared with you, which show that we have an immune response, which does recognize Delta as well as Omicron as well as a host of other variants.

現在就 - 我認為我們希望我推測隨著替代菌株的出現，持久保護會是什麼樣子。如你所知，我們沒有任何關於我與你分享的其他免疫原性數據的數據，這表明我們有免疫反應，它確實識別 Delta 以及 Omicron 以及許多其他變體。

Now if you remember back to the Atlas and efficacy data, that although we didn't have a lot of cases, that had a good estimate of efficacy against Delta, which is 82% and the lower bound of roughly 75%. And I think that's consistent with what the other sponsors have shown in their studies against Delta.

現在，如果您還記得 Atlas 和功效數據，儘管我們沒有很多案例，但對 Delta 的功效有一個很好的估計，即 82% 和大約 75% 的下限。我認為這與其他贊助商在針對達美航空的研究中所顯示的一致。

Our next question comes from Eric Joseph from JPMorgan.

我們的下一個問題來自摩根大通的 Eric Joseph。

Just one confirmatory one to start. Is there anything from your interactions with the FDA so far that would suggest that the EUA pass is not still open? I think a lot of investors are just looking for confirmation that the EUA path with Nuvaxovid is indeed open.

只需一個確認即可開始。到目前為止，您與 FDA 的互動中是否有任何跡象表明 EUA 通行證尚未開放？我認為很多投資者只是在尋求確認 Nuvaxovid 的 EUA 路徑確實是開放的。

And then secondly, as it relates to the nonclinical BLA requirements and needing to demonstrate law consistency runs, does it matter which facilities those are being generated at? Is Serum sufficient? Or would you need to conduct those in part using your own supply chain?

其次，由於它涉及非臨床 BLA 要求並需要證明法律一致性運行，這些在哪些設施生成是否重要？血清夠嗎？或者您是否需要部分使用您自己的供應鏈來執行這些操作？

So maybe I'll take the second part of the question and just to make the point that Serum is, in fact, part of our supply chain. And all of our global filings were harmonized to include the product and the manufacturing process out of Serum to be part of their filing. Now our application to the FDA includes the Serum as a manufacturer and therefore, the Lot-Lot consistency study has to be made for material made in Serum.

所以也許我會回答問題的第二部分，只是為了說明血清實際上是我們供應鏈的一部分。我們所有的全球文件都進行了協調，將 Serum 的產品和製造過程包括在他們的文件中。現在我們向 FDA 的申請包括作為製造商的血清，因此，必須對血清製成的材料進行批次一致性研究。

Okay.

好的。

And on the first -- this is Stan...

首先——這是斯坦……

The first question, it's EUA all the way. I mean I think both us and the agency are working towards getting an EUA for this product as fast as possible.

第一個問題，一路都是EUA。我的意思是我認為我們和該機構都在努力盡快為該產品獲得 EUA。

All right. And maybe just a follow-up to the second question. As it relates to manufacturing, I mean part of the prior communication was that you're expecting to supplement your supplement to regulatory bodies with additional CMC packages. Can you -- I guess is there any updated timing that you might be providing today?

好的。也許只是對第二個問題的跟進。由於它與製造有關，我的意思是之前的部分溝通是您希望通過額外的 CMC 包來補充您對監管機構的補充。你能 - 我猜你今天可能會提供任何更新的時間嗎？

No. I think that the first goal was accomplished with all the filings Well, first of all, Filip said that we harmonized all of our production, which is really important. Number two, our first filings has been with Serum because they are there with the volume that can service all of the various EUAs. And right after we get those EUAs, which as you recall, it's only been within the last weeks, we put together packages to file additional sites such as SK in Korea and our [CSD] facility. And so those will just be coming on time. It will be supplements to all of our filings. We'd like to have the flexibility to ship virtually anywhere from any of our plans.

不。我認為第一個目標是通過所有文件實現的 嗯，首先，菲利普說我們協調了我們所有的生產，這非常重要。第二，我們的第一份申請是使用 Serum，因為它們的數量可以為所有各種 EUA 提供服務。在我們得到那些 EUA 之後，正如你記得的那樣，這只是在過去幾週內，我們將包裹放在一起以提交其他站點，例如韓國的 SK 和我們的 [CSD] 設施。所以這些只會準時到來。它將是我們所有文件的補充。我們希望能夠靈活地從我們的任何計劃中運送到幾乎任何地方。

Okay. Just to clarify, finally, as it relates to just manufacturing. When it comes to at the plant in Prague, agreements with Fujifilm, Diosynth and like in terms of making API, I guess what is the -- what should be the current understanding of the integration of those facilities as part of the supply chain from all the commentary, everything seems sounds to be very heavily weighted towards Serum? I guess is there really -- effectively should we be thinking about those other facilities making API that I mentioned earlier are kind of factoring into the global supply chain?

好的。最後，澄清一下，因為它與製造有關。當談到在布拉格的工廠，與富士膠片、Diosynth 等就製造 API 達成的協議時，我猜想目前對將這些設施整合為供應鏈一部分的理解應該是什麼？評論，似乎一切聽起來都非常重視血清？我想是否真的存在——實際上我們是否應該考慮那些我之前提到的製造 API 的其他設施在某種程度上是全球供應鏈的因素？

Yes, they will. It's just -- we had -- somebody has to be first. Serum was there and ready and scaled up and producing very large quantities, but SK has made on the order of 100 million doses that will be folded into the supply chain very quickly. And same for Prague. And we're working -- we continue to work with Fuji.

是他們會。只是——我們有——必須有人成為第一。血清已經準備好並擴大規模並生產了非常大的數量，但 SK 已經生產了約 1 億劑的訂單，這些劑量將很快併入供應鏈。布拉格也一樣。我們正在努力——我們將繼續與富士合作。

So as I say, it gives us multiple options. We have done what we said we would do 2 years ago, which is to go from 0 manufacturing capacity to this level now, which frankly exceeds 2 billion doses a year. And so that gives us a lot of flexibility in terms of supplying any anticipated and unanticipated orders that we get from various governments. We're in good place.

正如我所說，它為我們提供了多種選擇。我們已經做了我們兩年前說要做的事情，就是從 0 製造能力到現在這個水平，坦率地說，每年超過 20 億劑。因此，在供應我們從各國政府獲得的任何預期和未預期的訂單方面，這給了我們很大的靈活性。我們在好地方。

(Operator Instructions) Our next question comes from David Risinger from SVB.

（操作員說明）我們的下一個問題來自 SVB 的 David Risinger。

So I have a few questions. The first is, could you just discuss the gross margin prospects for the company? And how we should think about gross margin? Because there are a lot of partners that you have and it's difficult to try to estimate what the various cost components would be from the various supply sources.

所以我有幾個問題。首先，你能談談公司的毛利率前景嗎？我們應該如何看待毛利率？因為你有很多合作夥伴，很難估計來自不同供應源的各種成本構成。

The second question is the release indicates that you initiated a Phase III booster study. When do you expect to generate data from that trial and file for Booster approval in the U.S.? And then the final question is for the Omicron-specific vaccine. For that, when do you plan to submit that for approval in the U.S. and -- both as a primary vaccine and also as a booster?

第二個問題是發布表明您啟動了 III 期加強研究。您預計何時從該試驗中生成數據並在美國提交 Booster 批准？最後一個問題是針對 Omicron 特異性疫苗的。為此，您計劃何時將其提交美國批准，並且作為主要疫苗和助推器？

So let me distribute this. First, we'll give it to Jim for the -- to talk about or not talk about our future margins, and then turn it over to Filip, if I could to address the others.

所以讓我分發這個。首先，我們將把它交給 Jim，讓他談論或不談論我們未來的利潤，然後交給 Filip，如果我可以解決其他人的話。

All right. So thanks for the question. And I'll start by saying gross margin as a percent of revenue is a little complicated because you have different price points, right? So you've got some degree of variability depending on the local market price. So perhaps easier to view it on in absolute terms. So we expect that we're going to have price or cost per unit in the, call it, $3 to $5 a dose range. But that said, you heard earlier that we've written off and expense a fair amount of inventory expense in 2021.

好的。所以謝謝你的問題。我首先要說毛利率佔收入的百分比有點複雜，因為你有不同的價格點，對吧？因此，根據當地市場價格，您會有一定程度的可變性。所以也許更容易從絕對角度來看待它。因此，我們預計每單位的價格或成本將在 3 到 5 美元/劑量範圍內。但話雖如此，您之前聽說我們已經在 2021 年註銷並支出了相當數量的庫存費用。

And so what that means is that as we move into 2022, begin to recognize sales and COGS, we're going to have periods of it's called 0 cost or low-cost COGS early on as we realized the benefit of manufacturing expenses that hit R&D in 2021.

所以這意味著，隨著我們進入 2022 年，開始認識到銷售和銷貨成本，我們將有一段時間被稱為零成本或低成本銷貨成本，因為我們意識到製造費用對研發的好處2021 年。

Okay. I think as I was outlining -- and boosting initially. And so I guess I'll start. So right now, we have the phase II study in Australia and the U.S., which we have in hand as well as the South African study, which is also boosting study. We know from our interactions with regulators that many consider this adequate to get a for-boosting indication. And we've had discussions with MHRA, EMA, TGA, and they all seem to have a pathway to use that data by itself.

好的。我認為正如我在概述 - 並最初提升。所以我想我會開始。所以現在，我們在澳大利亞和美國有第二階段的研究，我們手頭還有南非的研究，這也在促進研究。我們從與監管機構的互動中了解到，許多人認為這足以獲得提振跡象。我們已經與 MHRA、EMA、TGA 進行了討論，他們似乎都有自己使用這些數據的途徑。

Whether that's sufficient for the U.S., isn't clear? In case it isn't, we do have the boosting study, which we -- as ongoing from the 301 U.S. study where we boosted the participants. So that will be ready in due course. Now that study is started much later than the other 2. So that data wouldn't be available for a while. So in short, it's been really clear and that will be based on regulatory discussions with the FDA, whether the data that we plan to file in the first quarter -- or the second quarter, sorry, will be adequate to get a boosting indication in the U.S.

這對美國來說是否足夠，尚不清楚嗎？如果不是這樣，我們確實有增強研究，我們 - 從我們增強參與者的 301 美國研究中進行。所以這將在適當的時候準備好。現在該研究的開始時間比其他 2 晚得多。因此，該數據將在一段時間內無法獲得。所以簡而言之，這真的很清楚，這將基於與 FDA 的監管討論，我們計劃在第一季度或第二季度提交的數據，抱歉，是否足以在美國

I think you had a question that was similar to that about time lines of U.S. for Omicron. And we haven't disclosed when that study will read out.

我想你有一個類似於 Omicron 的美國時間線的問題。我們還沒有透露該研究何時宣讀。

Okay. And just a quickly follow-up on that. Will that include any assessment of a booster in that Omicron study that you just mentioned?

好的。只是對此的快速跟進。這是否包括對您剛才提到的 Omicron 研究中的助推器的任何評估？

Yes. It's a -- we haven't gone into detail into the design of that study. But in short, we're going to be looking at people who've been vaccinated with other people's vaccine, primarily because there are no more naive people left in this world. So that's the most relevant population to evaluate the vaccine. The study design we have in mind should be able to fill those data that's required for a boosting indication as well as for strain change. So it will be able to serve for this need.

是的。這是一個 - 我們還沒有詳細介紹該研究的設計。但簡而言之，我們將關注那些接種過其他人疫苗的人，主要是因為這個世界上不再有天真的人了。所以這是評估疫苗最相關的人群。我們考慮的研究設計應該能夠填充增強適應症和應變變化所需的那些數據。因此它將能夠滿足這一需求。

And ladies and gentlemen, with that, we'll conclude the question-and-answer session. I'd like to turn the conference call back over to Stan for any closing remarks.

女士們，先生們，我們將結束問答環節。我想把電話會議轉回給 Stan 做任何結束語。

Thank you. I think that people who have been following us for some time will recognize that this has been a very transformational quarter for us. We've -- we're a revenue-generating company. We've got obligations to support that revenue generation and report on that. We're very excited by this. We've now got manufacturing process that's been approved by virtually the world. We've got regularity to our shipping. We've got good cadence, and we're looking forward to every quarter talking with you more.

謝謝你。我認為關注我們一段時間的人們會認識到，這對我們來說是一個非常具有變革性的季度。我們 - 我們是一家創收公司。我們有義務支持創收並就此進行報告。我們對此感到非常興奮。我們現在擁有幾乎得到世界認可的製造工藝。我們的運輸有規律。我們的節奏很好，我們期待每個季度與您進行更多交流。

Thanks very much, and keep your questions coming. Talk soon.

非常感謝，請繼續提出您的問題。一會再聊。

Ladies and gentlemen, with that, we'll conclude today's conference call. We do thank you for attending. You may now disconnect your lines.

女士們，先生們，至此，我們將結束今天的電話會議。我們非常感謝您的出席。您現在可以斷開線路。