莫德納 (MRNA) 2022 Q1 法說會逐字稿

Good morning. My name is Kevin, and welcome to Moderna's First Quarter 2022 Earnings Call. (Operator Instructions) Please be advised that this call is being recorded.

早上好。我的名字是凱文，歡迎來到 Moderna 的 2022 年第一季度財報電話會議。 （操作員說明）請注意，此通話正在錄音中。

At this time, I'd like to turn the call over to Lavina Talukdar, Head of Investor Relations at Moderna. Please proceed.

此時，我想將電話轉給 Moderna 投資者關係主管 Lavina Talukdar。請繼續。

Thank you, Kevin. Good morning, everyone, and thank you for joining us on today's call to discuss Moderna's first quarter 2022 financial results and business updates. You can access the press release issued this morning as well as the slides that we'll be reviewing by going to the Investors section of our website. On today's call are Stephane Bancel, our Chief Executive Officer; David Meline, our Chief Financial Officer; Stephen Hoge, our President; and Paul Burton, our Chief Medical Officer.

謝謝你，凱文。大家早上好，感謝您加入我們今天的電話會議，討論 Moderna 2022 年第一季度的財務業績和業務更新。您可以訪問我們網站的“投資者”部分，訪問今天上午發布的新聞稿以及我們將審查的幻燈片。今天的電話是我們的首席執行官 Stephane Bancel；我們的首席財務官 David Meline；我們的總裁斯蒂芬·霍格；和我們的首席醫療官 Paul Burton。

Before we begin, please note that this conference call will include forward-looking statements made pursuant to the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. Please see Slide 2 of the accompanying presentation and our SEC filings for important risk factors that could cause our actual performance and results to differ materially from those expressed or implied in these forward-looking statements.

在我們開始之前，請注意，本次電話會議將包括根據 1995 年《私人證券訴訟改革法案》的安全港條款作出的前瞻性陳述。請參閱隨附演示文稿的幻燈片 2 和我們提交給 SEC 的重要風險因素可能導致我們的實際業績和結果與這些前瞻性陳述中明示或暗示的內容存在重大差異。

I will now turn the call over to Stephane.

我現在將把電話轉給 Stephane。

Thank you, Lavina. Good morning or good afternoon, everyone. Welcome to our Q1 2022 conference call. Today, I will start by a quick business review of the quarter before Paul walks you through an update on Spikevax real-world evidence, and then Stephen reviews our clinical programs. David will then present the key financials, and I will then come back to conclude before we take your questions.

謝謝你，拉維娜。大家早上好或下午好。歡迎參加我們的 2022 年第一季度電話會議。今天，在 Paul 向您介紹 Spikevax 真實世界證據的更新之前，我將首先對本季度的業務進行快速回顧，然後 Stephen 回顧我們的臨床項目。然後，大衛將介紹關鍵的財務狀況，然後在我們回答您的問題之前，我會回來總結一下。

I'm happy to share that the team delivered strong financial results this quarter. Revenues of $6.1 billion, GAAP net income of $3.7 billion and GAAP diluted EPS of $8.58. We ended Q1 with a cash balance of $19.3 billion. For our share buyback program, we continue to retire shares in Q1 like we already did in Q4. David will share some numbers on share count in a few minutes.

我很高興與大家分享，該團隊本季度取得了強勁的財務業績。收入為 61 億美元，GAAP 淨收入為 37 億美元，GAAP 攤薄後每股收益為 8.58 美元。我們在第一季度結束時的現金餘額為 193 億美元。對於我們的股票回購計劃，我們將繼續在第一季度退市，就像我們在第四季度所做的那樣。大衛將在幾分鐘內分享一些關於股票數量的數字。

For 2022, we are reiterating $21 billion in signed advanced purchase agreements. We have previously shared market share increases seen in the OECD countries with Spikevax when supply was no longer limited and when real-world publications highlighted differentiating data amongst the market vaccine. I'm happy to share that our market share has increased or still consistent across OECD countries.

對於 2022 年，我們重申已簽署 210 億美元的預購協議。我們之前曾與 Spikevax 分享了經合組織國家的市場份額增加，當時供應不再受到限制，並且現實世界的出版物強調了市場疫苗之間的差異化數據。我很高興與大家分享，我們的市場份額在經合組織國家中有所增加或保持一致。

While a subset of our team is focused on delivering on the $21 billion signed APAs for fiscal year 2022, another subset of our team is focused on preparing the next wave of product launches. With our flu vaccine candidate, mRNA-1010, plans to start a Phase III study in Q2 in the Southern Hemisphere, Moderna will have very soon 4 vaccine candidates in Phase III. An Omicron containing bivalent COVID booster, a flu booster, an RSV booster and the CMV vaccine.

雖然我們團隊的一部分專注於在 2022 財年交付價值 210 億美元的簽署 APA，但我們團隊的另一部分專注於準備下一波產品發布。隨著我們的流感疫苗候選藥物 mRNA-1010 計劃於第二季度在南半球開始 III 期研究，Moderna 很快將有 4 種候選疫苗進入 III 期。含有二價 COVID 加強劑、流感加強劑、RSV 加強劑和 CMV 疫苗的 Omicron。

Starting with our Omicron containing bivalent COVID booster, mRNA-1273.214, we could see up to 3 respiratory vaccine launches from the fall of 2022 over the next 2 to 3 years. We believe each of these 4 vaccine candidates in Phase III could have multibillion-dollar annual peak sales. And because they all use the exact same mRNA technology as our approved vaccine, Spikevax, we believe this pro-vaccine candidate in late-stage clinical trials have a high probability of success.

從我們的含有 Omicron 的二價 COVID 增強劑 mRNA-1273.214 開始，我們可以看到從 2022 年秋季開始在未來 2 到 3 年內推出多達 3 種呼吸道疫苗。我們認為，這 4 種處於 III 期的候選疫苗中的每一種都可能擁有數十億美元的年銷售峰值。而且因為它們都使用與我們批准的疫苗 Spikevax 完全相同的 mRNA 技術，我們相信這種在後期臨床試驗中的前疫苗候選者有很高的成功概率。

In addition to our 4 late-stage vaccine, we continue to expand the applications of mRNA technology beyond vaccines. We should have important proof-of-concept data in patients in 2 of our therapeutic modalities later this year. Propionic acidemia and methylmalonic acidemia in our rare genetic business portfolio, and the personalized cancer vaccine.

除了我們的 4 種後期疫苗，我們還在繼續擴大 mRNA 技術在疫苗之外的應用。今年晚些時候，我們應該在我們的兩種治療方式中獲得重要的概念驗證數據。我們罕見的基因業務組合中的丙酸血症和甲基丙二酸血症，以及個性化癌症疫苗。

Slide 7 shows the continued growth of Moderna. We now have 46 development programs in the pipeline. The organization has continued to grow to 3,200 team members.

幻燈片 7 顯示了 Moderna 的持續增長。我們現在有 46 個開發項目正在籌備中。該組織繼續增長到 3,200 名團隊成員。

With that, let me hand it over to Paul to review real-world evidence studies of our COVID booster. Paul?

有了這個，讓我把它交給保羅審查我們的 COVID 助推器的真實證據研究。保羅?

Thank you, Stephane, and hello, everyone. While there continues to be many studies posted and published on our mRNA vaccine, I would like to highlight some data today on vaccine boosting. But first, it's important to understand why booster vaccines are so critical as we transition through the COVID-19 pandemic and the understanding that we need to have about the evolution of the SARS-CoV-2 virus.

謝謝你，斯蒂芬，大家好。雖然仍有許多關於我們的 mRNA 疫苗的研究發表和發表，但我今天想強調一些關於疫苗加強免疫的數據。但首先，重要的是要了解為什麼加強疫苗在我們過渡到 COVID-19 大流行時如此重要，以及我們需要了解 SARS-CoV-2 病毒的進化。

On Slide 9, we can see the change in COVID-19 cases over time, with the massive rise we observed due to Omicron in the last weeks of 2021 in the early part of 2022. The Omicron wave was caused by BA.1. And while that was certainly the dominant version of SARS-CoV-2 at that time, remarkably, BA.1 is now almost extinct here in the United States and around the world having been replaced by new subvariants. This continues to demonstrate the remarkable evolutionary capacity of this virus.

在幻燈片 9 上，我們可以看到 COVID-19 病例隨時間的變化，我們在 2022 年初的 2021 年最後幾週觀察到由於 Omicron 的大量增加。Omicron 波是由 BA.1 引起的。雖然這在當時肯定是 SARS-CoV-2 的主要版本，但值得注意的是，BA.1 現在在美國和世界各地幾乎絕跡，已被新的子變體取代。這繼續證明了這種病毒的非凡進化能力。

BA.2 is now the dominant strain in the in the United States, with another subvariant of that BA.2.12.1 increasing rapidly, showing enhanced transmissibility. While BA.2 is dominant today, that increased transmissibility and infectivity of BA.2.12.1 is likely going to ensure it will be the dominant circulating strain very soon as we are seeing in New York and in the Northeast of the United States. Other new subvariants BA.4, BA.5, seen in South Africa, have also been detected in the United States, and we will need to carefully monitor their growth trajectories and pathogenicity.

BA.2 現在是美國的主要菌株，該 BA.2.12.1 的另一個子變體迅速增加，顯示出增強的傳播性。雖然今天 BA.2 占主導地位，但 BA.2.12.1 的傳播性和傳染性增加可能會確保它將很快成為我們在紐約和美國東北部看到的主要傳播菌株。在南非發現的其他新子變體 BA.4、BA.5 在美國也被發現，我們將需要仔細監測它們的生長軌跡和致病性。

The slowing of booster uptake now means there will be individuals who are undervaccinated and underprotected as we move into late spring and summer when we thought we would have declining case counts and balance, which could now be impacted by BA.2.12.1, BA.4 or BA.5. The speed and breadth of evolution of this virus that we see so clearly again today underpins our prediction for the global need for a varied adapted booster campaign this coming fall.

現在，加強劑攝取的放緩意味著隨著我們進入春末和夏季，當我們認為病例數和平衡會下降時，將會有一些人接種不足和保護不足，而現在這可能會受到 BA.2.12.1、BA 的影響。 4 或 BA.5。我們今天再次如此清楚地看到這種病毒的進化速度和廣度，這支持了我們對即將到來的秋天全球需要進行各種適應性增強運動的預測。

The good news is that a booster of vaccine protects against both BA.1 and BA.2. This is seen clearly when we look at data from the United Kingdom Health Security Agency. This graph looks at vaccine effectiveness against symptomatic disease for people who received the Moderna, Pfizer or AstraZeneca vaccine for their primary vaccination on the left. You can see that against both BA.1, Omicron and BA.2, vaccine effectiveness wanes over time. But a booster dose of either the Pfizer or Moderna mRNA vaccines increases vaccine effectiveness and protection, as you can see on the right.

好消息是，加強疫苗可以同時預防 BA.1 和 BA.2。當我們查看來自英國衛生安全局的數據時，可以清楚地看到這一點。這張圖表在左側顯示了接受 Moderna、輝瑞或阿斯利康疫苗作為主要疫苗接種的人的疫苗對症狀性疾病的有效性。您可以看到，針對 BA.1、Omicron 和 BA.2，疫苗的有效性會隨著時間的推移而減弱。但是，如右圖所示，輝瑞或 Moderna mRNA 疫苗的加強劑量可提高疫苗的有效性和保護性。

These 2 vaccines are combined together in this analysis. But again, even in this setting, there's gradual waning of vaccine effectiveness over time following boosting. This waning of vaccine effectiveness begs the question, will a second booster dose provide clinical utility and help to restore vaccine effectiveness and provide protection against COVID-19?

在此分析中將這兩種疫苗結合在一起。但同樣，即使在這種情況下，隨著時間的推移，疫苗的有效性也會隨著時間的推移而逐漸減弱。疫苗效力的這種減弱引出了一個問題，第二次加強劑量是否會提供臨床效用並有助於恢復疫苗效力並提供針對 COVID-19 的保護？

While there are several examples of studies showing the high clinical effectiveness of additional boosting with the Moderna vaccine, on Slide 11, I want to highlight the results of a recent study from Ontario that looked at exactly this question and measured the effectiveness between a first and second booster vaccine dose in a high-risk population, those people living in long-term care facilities.

雖然有幾個研究示例表明使用 Moderna 疫苗進行額外加強具有很高的臨床有效性，但在幻燈片 11 上，我想強調安大略省最近一項研究的結果，該研究正是針對這個問題並測量了第一次和第二次疫苗之間的有效性。在高危人群（居住在長期護理機構的人）中進行第二次加強疫苗接種。

A key finding from this study, which was conducted in over 55,000 individuals, was that indeed, a second boost of vaccination showed increased vaccine effectiveness against Omicron infections, symptomatic disease, and importantly, against severe outcomes in this high-risk setting. In fact, an increase in vaccine effectiveness was seen at 7 days from the second booster vaccination and continued to increase in effectiveness over time.

這項在超過 55,000 人中進行的研究的一個關鍵發現是，事實上，第二次加強疫苗接種顯示出疫苗對 Omicron 感染、症狀性疾病的有效性提高，而且重要的是，在這種高風險環境中，對嚴重後果的影響。事實上，在第二次加強接種後的第 7 天，疫苗的有效性出現了提高，並且隨著時間的推移，有效性繼續提高。

Turning now to Slide 12. I would like to provide a perspective on who might gain particular benefit from annual vaccine boosting. There are many health, age-related and environmental occupational risk factors that lead to populations being at higher risk for COVID-19. First, age greater than 50 years. We know that hospitalization and mortality rates begin to increase steeply for those with COVID-19 who are over the age of 50.

現在轉到幻燈片 12。我想就誰可能從每年的疫苗加強接種中獲得特別好處提供一個觀點。有許多健康、年齡相關和環境職業風險因素導致人群感染 COVID-19 的風險更高。第一，年齡大於50歲。我們知道，對於 50 歲以上的 COVID-19 患者，住院率和死亡率開始急劇上升。

And then turning to people over the age of 18 that have other health risk factors, such as people with kidney disease, cancer, autoimmune disease and HIV patients, other health factors that either result in immunocompromise or place people at higher physiological risk for severe disease, if indeed, they are infected with SARS-CoV-2.

然後轉向 18 歲以上有其他健康風險因素的人，例如患有腎病、癌症、自身免疫性疾病和 HIV 患者，其他健康因素會導致免疫功能低下或使人們面臨更高的嚴重疾病生理風險，如果確實如此，他們感染了 SARS-CoV-2。

Finally, environmental or occupational risk factors, such as health care workers, first responders, those in high-density housing or living conditions such as college students, military personnel or the incarcerated. We believe it is people in these broad categories who could benefit most from annual boosting for COVID-19.

最後，環境或職業風險因素，如衛生保健工作者、急救人員、高密度住房或生活條件中的人，如大學生、軍人或被監禁者。我們認為，這些廣泛類別的人可以從 COVID-19 的年度提升中受益最大。

And so in summary, we've seen as we continue to anticipate SARS-CoV-2 to keep evolving rapidly with multiple new variants and recombinant variants circulating globally. Real-world evidence demonstrates the effectiveness of a booster shot, a third dose of mRNA-1273 against evolving variants of concern. And an additional booster, a fourth dose of mRNA-1273 shows incremental vaccine effectiveness when compared to a third dose against infection, symptomatic infection and severe disease in a high-risk population.

總而言之，我們已經看到，隨著我們繼續預期 SARS-CoV-2 將隨著多種新變體和重組變體在全球範圍內傳播而迅速發展。現實世界的證據證明了加強注射的有效性，即第三劑 mRNA-1273 對抗不斷演變的關注變體。此外，與第三劑相比，第四劑 mRNA-1273 在高危人群中對感染、症狀性感染和嚴重疾病的疫苗有效性增加。

We believe people are at high risk due to health, age and environmental or occupational risk factors. And we believe that when taken together with the viral epidemiology and waning of protection, there is an important need for a variant-adapted booster vaccine and for boosting of populations this coming fall.

我們認為，由於健康、年齡和環境或職業風險因素，人們處於高風險之中。我們相信，當考慮到病毒流行病學和保護的減弱時，非常需要一種適應變體的加強疫苗，並在即將到來的秋季增加人口數量。

With that, I'll now turn it over to Stephen to take you through the progress in our clinical development pipeline. Stephen?

有了這個，我現在將把它交給斯蒂芬，帶你了解我們臨床開發管道的進展。斯蒂芬?

Thanks, Paul. Good morning and good afternoon, everyone. Paul just shared with you the effectiveness of our booster mRNA-1273 against Omicron in the real-world setting. But on Slide 15, I'd like to pivot to our strategic rationale for why we think a seasonal booster will be necessary.

謝謝，保羅。大家早上好，下午好。 Paul 剛剛與您分享了我們的增強型 mRNA-1273 在現實環境中對抗 Omicron 的有效性。但在幻燈片 15 上，我想談談我們為什麼認為需要季節性助推器的戰略理由。

So first, we think neutralizing titers will wane similar to the endemic human coronaviruses. And that decline in neutralizing titers will increase their risk of breakthrough infection and hospitalization for those at higher risk, particularly as Paul just described, older adults or those with medical -- immunocompromised. The emergence of new variants of concern like the BA.4, .5 subvariants could accelerate the impact of that waning and broaden the risk of breakthrough across the population. So with that, we do believe a booster will be needed in the fall, and we're working hard to make improvements to our available boosters.

因此，首先，我們認為中和滴度會像地方性人類冠狀病毒一樣減弱。而中和滴度的下降將增加他們突破性感染和住院風險較高的人的風險，特別是正如保羅剛剛描述的那樣，老年人或有醫學-免疫功能低下的人。 BA.4、.5 子變體等新變體的出現可能會加速這種減弱的影響並擴大整個人群的突破風險。因此，我們確實相信秋季將需要一個助推器，我們正在努力改進我們可用的助推器。

The desired features for a Northern Hemisphere fall-winter booster, we think will be that it improves the durability of protective neutralizing antibodies against Omicron and its subvariants beyond 6 months, i.e., the full Northern Hemisphere fall and winter infection season. We'd like to retain high and durable protection against Deltas and ancestral strains, and we'd like to broaden cross-protective immunity to increase the potential for protection against new emerging variants or subvariants that might happen over the coming months.

北半球秋冬助推器的理想特性是，我們認為它將提高針對 Omicron 及其子變體的保護性中和抗體的持久性超過 6 個月，即整個北半球秋冬感染季節。我們希望保留對 Deltas 和祖先菌株的高度和持久的保護，並且我們希望擴大交叉保護免疫，以增加針對未來幾個月可能發生的新出現的變體或亞變體的保護潛力。

So on Slide 16, I'd like to summarize our work in developing that improved booster. Our primary focus, as you know, has been on developing a bivalent vaccine, and we have taken 3 bivalents into clinical trials. The first mRNA-1273.211 includes 9 of the common mutations and was based on a combination of our prototype wild-type vaccine and Beta. The mRNA-1273.213 bivalent included 11 mutations based on what had emerged from Beta and Delta. And our mRNA-1273.214 booster includes 32 mutations, also now based on the wild-type prototype vaccine and the combination with the Omicron original variant of concern.

所以在幻燈片 16 上，我想總結一下我們在開發改進的助推器方面所做的工作。如您所知，我們的主要重點是開發二價疫苗，我們已將 3 種二價疫苗用於臨床試驗。第一個 mRNA-1273.211 包括 9 個常見突變，是基於我們的原型野生型疫苗和 Beta 的組合。 mRNA-1273.213 二價包括 11 個基於 Beta 和 Delta 出現的突變。我們的 mRNA-1273.214 加強劑包括 32 個突變，現在也是基於野生型原型疫苗以及與 Omicron 原始變體的組合。

Our latest bivalent, mRNA-1273.214 that includes those 32 mutations that have emerged remains our lead candidate for the fall Northern Hemisphere campaign. The objective of that booster will be to demonstrate superior immunogenicity against variants of concern when it compares to our approved current prototype booster or mRNA-1273 at 50 micrograms. And of course, we want to maintain noninferiority against ancestral strains in case they reemerge.

我們最新的二價 mRNA-1273.214 包括已經出現的 32 個突變，仍然是我們秋季北半球運動的主要候選人。與我們批准的當前原型增強劑或 50 微克的 mRNA-1273 相比，該增強劑的目的是證明對關注變體的優越免疫原性。當然，我們希望保持對祖先品系的非劣效性，以防它們再次出現。

Now on Slide 17, I'll summarize the ongoing clinical development work across that portfolio of bivalent boosters. I'll remind you that mRNA-1273 has been authorized or approved in many markets as a third and even a fourth booster. The data for the first bivalent, mRNA 211 has already demonstrated superiority against all variants of concerns tested, including Omicron and Delta, and I'll cover that data in just a moment. But our lead candidate remains, as I said a moment ago, our mRNA-1273.214, which is being evaluated in 2 separate studies, a Phase II/III in the United States and a Phase III P305 study in United Kingdom. Again, both of those are being conducted at a booster dose of 50 micrograms.

現在在幻燈片 17 上，我將總結該二價增強劑組合正在進行的臨床開發工作。我會提醒您，mRNA-1273 已在許多市場上被授權或批准為第三甚至第四助推器。第一個二價 mRNA 211 的數據已經證明了對所有測試的關注點變體的優勢，包括 Omicron 和 Delta，我將在稍後介紹這些數據。但正如我剛才所說，我們的主要候選人仍然是我們的 mRNA-1273.214，它正在兩項獨立研究中進行評估，一項在美國進行的 II/III 期研究和一項在英國進行的 III 期 P305 研究。同樣，這兩項都是以 50 微克的加強劑量進行的。

Now on Slide 18, just quickly to update you on the data we have from the 211 first bivalent. Not surprisingly, the safety and reactogenicity profile of the bivalent boosters is consistent with what we saw with mRNA-1273. As you'll see on the chart, both solicited adversary local reactions and systemic reactions are broadly consistent in both frequency and severity. And the frequency and types of unsolicited adverse events were also comparable between the groups with no serious adverse events in the bivalent vaccine group up to 28 days after the booster dose.

現在在幻燈片 18 上，快速向您更新我們從 211 第一二價獲得的數據。毫不奇怪，二價增強劑的安全性和反應原性與我們在 mRNA-1273 中看到的一致。正如您將在圖表中看到的，請求的對手局部反應和全身反應在頻率和嚴重程度上大致一致。並且在加強劑量後長達 28 天的二價疫苗組中，無嚴重不良事件的組之間未經請求的不良事件的頻率和類型也具有可比性。

Moving to Slide 19. We have some of the neutralizing antibody data from that study, evaluating again, our mRNA-1273.211 bivalent and comparing that with an approved or authorized mRNA-1273 booster. Looking at neutralizing titers and GMTs, both immediately pre-booster at 1 month or day 29 at 6 months on day 181, across the 3 variants of concern which we tested, higher neutralizing titers were seen for day 29 and day 181 across all the variants of concern with the bivalent booster.

轉到幻燈片 19。我們有一些來自該研究的中和抗體數據，再次評估我們的 mRNA-1273.211 二價，並將其與批准或授權的 mRNA-1273 增強劑進行比較。查看中和滴度和 GMT，在我們測試的 3 個關注變體中，在第 181 天的第 1 個月或第 29 天在第 181 天立即預加強，在第 29 天和第 181 天觀察到更高的中和滴度在所有變體中與二價助推器有關。

On Slide 20, we represent that as a ratio and comparing the performance of the bivalent booster to mRNA-1273 at 1 month and 6 months, and superiority was met for the ancestral and all variants of concern at different time points, as you'll note here. The clinical endpoint for superiority was defined as a geometric mean titer ratio, or GMR, where the lower bound excluded -- the lower bound of the 95% confidence interval excluding one.

在幻燈片 20 上，我們將其表示為比率並比較二價增強劑與 mRNA-1273 在 1 個月和 6 個月時的性能，並且在不同時間點滿足祖先和所有關注變體的優勢，因為你會注意這裡。優越性的臨床終點被定義為幾何平均滴度比或 GMR，其中不包括下限 - 95% 置信區間的下限不包括一個。

And as you'll note, at day 29, a GMR for the ancestral SARS-CoV-2 virus was 1.28; Beta was 1.3; Delta was 1.75; and importantly, Omicron was as high as 2.2. And the 95% confidence interval for Omicron, the lower bound was 1.74, again, demonstrating strong trend towards superiority in this data. Excitingly, at day 181 or 6 months, that superiority was also met for the ancestral virus, Beta and the Omicron variant, which is important because the primary goal we have here is to improve the durability of protection by increasing those titers.

您會注意到，在第 29 天，祖先 SARS-CoV-2 病毒的 GMR 為 1.28； Beta 為 1.3； Delta 為 1.75；重要的是，Omicron 高達 2.2。 Omicron 的 95% 置信區間下限為 1.74，再次表明該數據具有強大的優勢趨勢。令人興奮的是，在第 181 天或第 6 個月時，祖先病毒、Beta 和 Omicron 變體也達到了這種優勢，這很重要，因為我們在這裡的主要目標是通過增加這些滴度來提高保護的持久性。

So on Slide 21, in conclusion, the safety and reactogenicity profile of the 50-microgram bivalent 211 booster was comparable to the 50-microgram of the authorizer-approved 1273 booster. And we believe that the superiority already demonstrated by the bivalent platform in 211 bodes well for our overall strategy. We continue to believe that bivalent boosters will ensure the broadest immunity across the evolutionary certainty of SARS-CoV-2 and maintain current protection while expanding the breadth and durability of neutralizing antibodies, including, as I just demonstrated a moment ago with 211, out to 6 months. We anticipate the 1 month or day 29 data from our Omicron containing bivalent mRNA-1273.214 in June of 2022.

因此，在幻燈片 21 上，總而言之，50 微克二價 211 加強劑的安全性和反應原性與授權人批准的 1273 加強劑的 50 微克相當。我們相信，211 二價平台已經展現出的優勢對我們的整體戰略來說是個好兆頭。我們仍然相信，二價增強劑將確保在 SARS-CoV-2 的進化確定性中獲得最廣泛的免疫力，並保持當前的保護，同時擴大中和抗體的廣度和持久性，包括，正如我剛才用 211 演示的那樣， 6個月。我們預計 2022 年 6 月我們的 Omicron 包含二價 mRNA-1273.214 的 1 個月或第 29 天數據。

Now turning to the rest of our respiratory vaccine pipeline on Slide 23. We announced positive Phase II data from our flu vaccine, mRNA-1010 at our Vaccines Day event. mRNA-1010 is our -- is part of our speed-to-market approach. We plan to start a Phase III immunogenicity study in the second quarter of this year and a Phase III efficacy trial later this year with mRNA-1010. As part of our flu vaccine strategy, we are also advancing in parallel, vaccine candidates that contain both HA antigens and NA antigens. We started a Phase I/II trial of mRNA-1020 and mRNA-1030 last month.

現在轉向幻燈片 23 上我們呼吸系統疫苗管道的其餘部分。我們在疫苗日活動中宣布了流感疫苗 mRNA-1010 的 II 期陽性數據。 mRNA-1010 是我們的 - 是我們加快上市速度的一部分。我們計劃在今年第二季度開始一項 III 期免疫原性研究，並在今年晚些時候使用 mRNA-1010 進行一項 III 期療效試驗。作為我們流感疫苗戰略的一部分，我們也在同時推進同時包含 HA 抗原和 NA 抗原的候選疫苗。我們上個月開始了 mRNA-1020 和 mRNA-1030 的 I/II 期試驗。

Our RSV vaccine, mRNA-1345, a Phase III trial in older adults is ongoing, and we are enrolling participants worldwide. We also have an ongoing pediatric RSV trial enrolling as well. In combinations, we plan to start a Phase I trial for both our COVID plus flu and our COVID flu RSV vaccines this year. Our Phase I trial for the hMPV/PIV3 combination vaccine is also now fully enrolled. And our RSV and HMPV combo and our endemic human coronavirus vaccine combo are in preclinical.

我們的 RSV 疫苗 mRNA-1345 正在進行一項針對老年人的 III 期試驗，我們正在全球範圍內招募參與者。我們還有一項正在進行的兒科 RSV 試驗正在招募中。結合起來，我們計劃今年開始對我們的 COVID plus 流感和我們的 COVID 流感 RSV 疫苗進行 I 期試驗。我們的 hMPV/PIV3 聯合疫苗的 I 期試驗現在也已完全註冊。我們的 RSV 和 HMPV 組合以及我們的地方性人類冠狀病毒疫苗組合處於臨床前階段。

Before moving from respiratory vaccines, I wanted to take a step back and reflect on the incredible progress over the past 2 years. We have or will have progressed 3 candidates into pivotal Phase III studies within 1 year of an IND being opened. This speed is made possible by our mRNA platform. And we believe our COVID vaccine success has derisked our vaccine pipeline, and we can now move quickly into our RSV and flu pivotal studies. Importantly, in RSV and flu, we are looking at seasonal endpoints or immunogenicity endpoints, which we believe can be -- can allow us to progress faster through Phase III towards its readouts and ultimately to commercialization.

在從呼吸道疫苗轉向之前，我想退後一步，反思過去 2 年中令人難以置信的進步。在 IND 開放後的 1 年內，我們已經或將有 3 名候選人進入關鍵的 III 期研究。我們的 mRNA 平台使這種速度成為可能。而且我們相信我們的 COVID 疫苗成功已經使我們的疫苗管道脫險，我們現在可以迅速進入我們的 RSV 和流感關鍵研究。重要的是，在 RSV 和流感中，我們正在研究季節性終點或免疫原性終點，我們相信這可以讓我們更快地通過 III 期讀數並最終實現商業化。

Now turning to the rest of our pipeline. We have an ongoing Phase III study for our CMV vaccine, mRNA-1647, which is enrolling well and is now enrolling participants globally. Our EBV vaccine to prevent infectious mononucleosis is in Phase I, and our EBV vaccine to prevent long-term sequela such as multiple sclerosis is in preclinical studies. Our HIV vaccines are in Phase I clinical trials with our partners. And the recently announced HSV and VZV vaccines are in preclinical studies.

現在轉向我們管道的其餘部分。我們正在進行一項針對 CMV 疫苗 mRNA-1647 的 III 期研究，該疫苗的招募情況良好，目前正在全球招募參與者。我們用於預防傳染性單核細胞增多症的 EBV 疫苗處於 I 期，我們用於預防多發性硬化症等長期後遺症的 EBV 疫苗處於臨床前研究中。我們的 HIV 疫苗正在與我們的合作夥伴進行 I 期臨床試驗。最近宣布的 HSV 和 VZV 疫苗正在臨床前研究中。

Within public health vaccines, our Zika vaccine continues to enroll in Phase II. And we are pleased to update that our Nipah virus vaccine, IND, was opened, and we look forward to starting that trial soon with our partner.

在公共衛生疫苗中，我們的寨卡疫苗繼續進入第二階段。我們很高興地更新我們的尼帕病毒疫苗 IND 已經開放，我們期待與我們的合作夥伴盡快開始該試驗。

Now moving to our therapeutic pipeline on Slide 26. Within oncology, our personalized cancer vaccine is ongoing in a Phase I study and a Phase II study. And we expect the first look at the data from our Phase II study, which is evaluating personalized cancer vaccine plus KEYTRUDA versus KEYTRUDA alone, in the fourth quarter of this year. We have 4 other candidates in Phase I or preclinical stages across oncology.

現在轉到幻燈片 26 上的治療管道。在腫瘤學領域，我們的個性化癌症疫苗正在進行 I 期研究和 II 期研究。我們預計將在今年第四季度首次查看我們 II 期研究的數據，該研究正在評估個性化癌症疫苗加 KEYTRUDA 與單獨的 KEYTRUDA。我們在腫瘤學的 I 期或臨床前階段有 4 名其他候選人。

In cardiovascular and autoimmune, we have 2 candidates in each area in clinical trials or in the preclinical stage. And within rare diseases, our propionic acidemia program, or PA program for short, which I will give more detail on the next slide, is ongoing in a Phase I/II study. Our MMA program is also ongoing in the Phase I/II study. And our GSD1a program has an open IND and we look forward to enrolling the first participants in that study. We have 3 other candidates in preclinical and rare disease as well.

在心血管和自身免疫方面，我們在臨床試驗或臨床前階段的每個領域都有 2 名候選人。在罕見疾病中，我們的丙酸血症計劃或簡稱 PA 計劃（我將在下一張幻燈片中提供更多詳細信息）正在進行 I/II 期研究。我們的 MMA 項目也正在進行 I/II 期研究。我們的 GSD1a 計劃有一個開放的 IND，我們期待著招募該研究的第一批參與者。我們還有其他 3 名臨床前和罕見疾病的候選人。

Now before I hand it off to David, on Slide 27, I wanted to provide a bit more color on our Phase I/II study in propionic acidemia. As a reminder, PA is a rare metabolic disorder that is characterized by a deficiency of propionyl-CoA carboxylase, an enzyme that's involved in the breakdown of several of the building blocks of proteins called amino acids. As a result, a deficiency in that enzyme, harmful intermediate compounds can build up to toxic levels in the body. This can lead to serious health problems, including recurrent episodes of life-threatening metabolic decompensation events.

現在，在我把它交給大衛之前，在幻燈片 27 上，我想為我們的丙酸血症 I/II 期研究提供更多的色彩。提醒一下，PA 是一種罕見的代謝紊亂，其特徵是缺乏丙酰輔酶 A 羧化酶，這種酶參與分解稱為氨基酸的蛋白質的幾種組成部分。結果，缺乏這種酶，有害的中間化合物會在體內積累到毒性水平。這可能導致嚴重的健康問題，包括反復發作的危及生命的代謝失代償事件。

Our therapy for PA encodes for 2 of those proteins that form the deficient enzyme, PCCA and PCCB, and has 1 mRNA for each in the drug. The Phase I/II study is an adaptive trial design, enrolling participants greater than 1 years of age in the United States, United Kingdom and Canada. Participants received 1 dose of mRNA-3927 every 2 or every 3 weeks for up to 10 doses in that study.

我們的 PA 療法編碼了 2 種形成缺陷酶的蛋白質，PCCA 和 PCCB，並且在藥物中每種蛋白質都有 1 個 mRNA。 I/II 期研究是一項適應性試驗設計，在美國、英國和加拿大招募 1 歲以上的參與者。在該研究中，參與者每 2 週或每 3 週接受 1 劑 mRNA-3927，最多 10 劑。

The first cohort is fully enrolled, and we are now enrolling patients in the additional cohorts. Five patients have now completed the initial 10-dose course of the study and became eligible for continuing dosing in the open-label extension. And all 5 of those patients have elected to participate in the OLE. A total of 75 doses have now been administered across Phase I/II and the OLE study.

第一個隊列已完全註冊，我們現在正在將患者納入其他隊列。五名患者現已完成最初的 10 劑研究過程，並有資格在開放標籤擴展中繼續給藥。所有 5 名患者都選擇參加 OLE。現在在 I/II 期和 OLE 研究中總共施用了 75 劑。

Now the study is focused on evaluating safety and PK/PD. It is also looking at clinical events, those that are most important, including the metabolic decompensation events I mentioned previously. And of course, we are also evaluating potential biomarkers in the study. We look forward to enrolling more patients and sharing the data this year.

現在該研究的重點是評估安全性和 PK/PD。它還關注最重要的臨床事件，包括我之前提到的代謝失代償事件。當然，我們還在研究中評估潛在的生物標誌物。我們期待今年招募更多患者並分享數據。

And with that, I'd like to turn this over to our financial review from David.

有了這個，我想把它交給大衛的財務審查。

Okay. Thank you, Stephen. We're providing today the analysis of actual 2022 first quarter results, along with a view of key drivers of financial performance going forward. Overall, we had a good start to 2022, and I'm very pleased with our operational and commercial performance.

好的。謝謝你，斯蒂芬。我們今天提供對 2022 年第一季度實際業績的分析，以及對未來財務業績的關鍵驅動因素的看法。總體而言，我們在 2022 年有一個良好的開端，我對我們的運營和商業表現感到非常滿意。

Turning now to Slide 29, starting with an overview of our sales performance. Total product sales in the first quarter of 2022 were $5.9 billion. This compares to product sales of $1.7 billion in the first quarter of 2021. The total sales growth is driven by the fact that we were in an earlier stage of our manufacturing ramp-up in Q1 of last year, with our U.S.-based manufacturing lines roughly 3 months ahead of our international manufacturing capabilities. This also explains the different geographic sales mix. In the first quarter of 2022, sales outside the U.S. were $5 billion, and sales to the U.S. government were $0.9 billion. The majority of sales in Q1 of last year were to the U.S. government.

現在轉到幻燈片 29，從我們的銷售業績概述開始。 2022 年第一季度的產品總銷售額為 59 億美元。相比之下，2021 年第一季度的產品銷售額為 17 億美元。總銷售額增長是由於我們在去年第一季度處於製造增長的早期階段，我們的生產線位於美國比我們的國際製造能力提前大約 3 個月。這也解釋了不同地域的銷售組合。 2022年第一季度，美國以外的銷售額為50億美元，對美國政府的銷售額為9億美元。去年第一季度的大部分銷售額是針對美國政府的。

Turning to Slide 30 to go into more detail of our Q1 results. Total revenue was $6.1 billion in the first quarter of 2022 compared to $1.9 billion in Q1 of last year. The increase of total revenue was driven by the sale of our COVID-19 vaccine. Cost of sales was $1 billion or 17% of the company's product sales in the first quarter. Cost of sales in percent of sales in Q1 of last year was 11% on a reported basis and 22% on adjusted for prelaunch inventory costs, which were expensed in 2020.

轉到幻燈片 30 以更詳細地了解我們的第一季度業績。 2022 年第一季度的總收入為 61 億美元，而去年第一季度為 19 億美元。總收入的增長是由我們的 COVID-19 疫苗的銷售推動的。第一季度銷售成本為 10 億美元，占公司產品銷售額的 17%。去年第一季度銷售成本佔銷售額的百分比為 11%，經調整後的發布前庫存成本為 22%，這些成本於 2020 年計入費用。

Compared to the prior year adjusted 22%, we are benefiting this quarter from an increased average selling price driven by customer mix, favorable impacts from the scale-up of our manufacturing processes, partially offset by higher write-downs for excess and obsolescence inventory and a current period expense related to future purchase commitments.

與去年調整後的 22% 相比，本季度我們受益於客戶組合推動的平均銷售價格上漲，我們製造流程擴大的有利影響，部分被過剩和過時庫存的更高減記抵消，以及與未來採購承諾相關的當期費用。

Research and development expenses were $554 million in the first quarter of 2022 compared to $401 million in the same period in 2021. The increasing R&D spend continues to be driven by clinical trial expenses for our expanding and maturing development portfolio.

2022 年第一季度的研發費用為 5.54 億美元，而 2021 年同期為 4.01 億美元。不斷增長的研發支出繼續受到我們不斷擴大和成熟的開發組合的臨床試驗費用的推動。

Selling, general and administrative expenses were $268 million for Q1 2022 compared to $77 million for the same period in 2021. The growth in spending was driven by the commercialization of our COVID-19 vaccine globally, with continued investments in personnel and outside services in support of the accelerated company build-out. Our Q1 2022 results also include the initial upfront endowment of $50 million for the newly established Moderna Foundation.

2022 年第一季度的銷售、一般和管理費用為 2.68 億美元，而 2021 年同期為 7700 萬美元。支出的增長是由我們的 COVID-19 疫苗在全球的商業化推動的，並持續投資於人員和外部服務以提供支持加速公司建設。我們 2022 年第一季度的業績還包括為新成立的 Moderna 基金會提供的 5000 萬美元的初始預付款。

Provision for income taxes was $572 million in the first quarter of 2022 compared to $39 million in the prior year period. Our effective tax rate for the first quarter was 14%. Let me remind you of the fact that we had a net operating loss carryforward of $2.3 billion at the end of 2020, which resulted in a nonrecurring benefit to the reported tax rate last year.

2022 年第一季度的所得稅準備金為 5.72 億美元，而去年同期為 3900 萬美元。我們第一季度的有效稅率為 14%。讓我提醒您一個事實，我們在 2020 年底有 23 億美元的淨營業虧損結轉，這導致去年報告的稅率產生了非經常性收益。

We recorded after-tax net income of $3.7 billion in Q1 compared to $1.2 billion in the prior year. Diluted earnings per share in Q1 2022 were $8.58. As a final point on the quarter and beyond, we currently do not have any commercial activities or R&D activities in the Ukraine or Russia.

我們在第一季度的稅後淨收入為 37 億美元，而去年為 12 億美元。 2022 年第一季度的稀釋後每股收益為 8.58 美元。作為本季度及以後的最後一點，我們目前在烏克蘭或俄羅斯沒有任何商業活動或研發活動。

Turning to cash and cash deposits on Slide 31. We ended Q1 2022 with cash and investments of $19.3 billion compared to $17.6 billion at the end of 2021. The increase is driven by our commercial activities. The balance of cash deposits for future product supply was $5.3 billion compared to $6 billion at the end of 2021. The reduction quarter-over-quarter is driven by product deliveries against customer deposits.

轉向幻燈片 31 上的現金和現金存款。截至 2022 年第一季度，我們的現金和投資為 193 億美元，而 2021 年底為 176 億美元。增長是由我們的商業活動推動的。用於未來產品供應的現金存款餘額為 53 億美元，而 2021 年底為 60 億美元。環比減少是由於產品交付與客戶存款相對應。

Now turning to Slide 32. Our capital allocation priorities remain unchanged. Our top investment priority has been and will continue to be reinvesting in the base business across multiple areas. For R&D, we continue to forecast to spend in the range of $2.5 billion to $3 billion in order to advance and accelerate our pipeline, both for existing and new programs.

現在轉到幻燈片 32。我們的資本配置重點保持不變。我們的首要投資重點一直是並將繼續在多個領域對基礎業務進行再投資。對於研發，我們繼續預測將花費 25 億至 30 億美元，以推進和加速我們現有和新項目的管道。

Our second investment priority is to seek attractive external investment and collaboration opportunities to further expand the reach of Moderna's technology and capabilities. We are considering attractive opportunities that enable and complement our platform and take a disciplined approach in evaluating potential outside investments. We're in multiple active discussions regarding additional external collaboration opportunities.

我們的第二個投資重點是尋求有吸引力的外部投資和合作機會，以進一步擴大 Moderna 的技術和能力範圍。我們正在考慮具有吸引力的機會，以支持和補充我們的平台，並採取嚴格的方法評估潛在的外部投資。我們正在就額外的外部合作機會進行多次積極討論。

After evaluating internal and external investment opportunities, we then assess additional uses of cash. We completed our initial $1 billion share buyback program in January and announced a new share buyback program of $3 billion in February. Across these 2 authorizations, we repurchased a total of 3.8 million shares for $0.6 billion during the first quarter.

在評估內部和外部投資機會後，我們會評估現金的其他用途。我們在 1 月份完成了最初的 10 億美元股票回購計劃，並在 2 月份宣布了一項 30 億美元的新股票回購計劃。在這兩項授權中，我們在第一季度以 6 億美元的價格回購了總計 380 萬股股票。

The next slide shows a progression of our share count since we initiated our share repurchase program. As a reminder, we received board approval for our initial $1 billion share repurchase program in August 2021 and began repurchasing shares in the fourth quarter of 2021. Our quarter-end basic shares outstanding declined from 405 million at the end of September 2021 to 400 million at the end of March 2022.

下一張幻燈片顯示了自我們啟動股票回購計劃以來我們的股票數量的進展情況。提醒一下，我們於 2021 年 8 月獲得了董事會批准我們最初的 10 億美元股票回購計劃，並於 2021 年第四季度開始回購股票。我們的季度末基本流通股從 2021 年 9 月底的 4.05 億股下降至 4 億股2022 年 3 月末。

We repurchased 7 million shares, more than offsetting 2 million shares of common stock issued in connection with equity compensation over this period. Our diluted weighted average shares outstanding also declined from 434 million in the third quarter of 2021 to 426 million in the first quarter of 2022, primarily as a result of the share repurchase activity.

我們回購了 700 萬股，超過了在此期間因股權補償而發行的 200 萬股普通股。我們的稀釋加權平均流通股也從 2021 年第三季度的 4.34 億股下降至 2022 年第一季度的 4.26 億股，這主要是由於股票回購活動。

Now let's turn to 2022 financial framework on Page 34. We have signed advanced purchase agreements for expected delivery in 2022 in the amount of approximately $21 billion. There's a potential downside to this number from timing of COVAX deliveries if COVAX is unable to confirm demand aligned to their contracted volume in the 2022 calendar year. There is also an upside to this number from potential additional contracts for the fall booster dose, including for the U.S. market.

現在讓我們轉到第 34 頁的 2022 年財務框架。我們已簽署預購協議，預計在 2022 年交付，金額約為 210 億美元。如果 COVAX 無法確認與 2022 日曆年的合同量相符的需求，那麼從 COVAX 交付時間來看，這個數字可能會下降。這個數字還有一個好處，那就是秋季加強劑量的潛在額外合同，包括美國市場。

In 2022, we believe that the SARS-CoV-2 virus will evolve into an endemic phase with a more seasonal sales pattern. As a result, we continue to expect the timing of sales to be larger in the second half of 2022 than in the first half.

2022 年，我們認為 SARS-CoV-2 病毒將演變為流行階段，銷售模式更具季節性。因此，我們繼續預計 2022 年下半年的銷售時機將大於上半年。

Our total cost of sales includes the cost of goods manufactured, third-party royalties as well as logistics and warehousing costs. We continue to expect cost of sales as a percent of product sales to increase compared to prior year, driven by both a decrease in our average selling price and a forecasted increase in manufacturing cost. The year-on-year decrease in average selling price is due to the higher share of COVAX APAs for delivery this year compared to last year.

我們的總銷售成本包括商品製造成本、第三方特許權使用費以及物流和倉儲成本。我們繼續預計銷售成本佔產品銷售額的百分比將比上一年增加，這主要是由於我們的平均銷售價格下降和製造成本的預測增加。平均售價同比下降的原因是今年交付的 COVAX APA 份額高於去年。

As the COVID-19 pandemic evolves into an endemic phase, we forecast our manufacturing unit costs to increase. This is driven by a move to smaller dose presentations and the cost for adjusting our production and supply chain infrastructure, including future purchase commitments. We continue to expect our full year 2022 reported cost of sales in the low to mid-20% range, which incorporates all the expected adjustments that we've identified for the 2022 calendar year. The cost of sales for Spikevax beyond 2022 will be further impacted by geographic customer mix, the pricing effects of the private market as it develops as well as our initiatives to optimize and improve efficiency.

隨著 COVID-19 大流行演變為流行階段，我們預測我們的製造單位成本將會增加。這是由向更小劑量展示的轉變以及調整我們的生產和供應鏈基礎設施的成本推動的，包括未來的採購承諾。我們繼續預計我們 2022 年全年報告的銷售成本在 20% 到中低範圍內，其中包含我們為 2022 日曆年確定的所有預期調整。 Spikevax 2022 年以後的銷售成本將進一步受到地域客戶組合、私人市場發展的定價效應以及我們優化和提高效率的舉措的影響。

For R&D and SG&A, we continue to expect full year expenses to be approximately $4 billion, driven by our maturing development portfolio and the global scale up of the company. Based on current tax laws, we continue to expect our 2022 tax rate to be in the mid-teens as a result of the benefits from the foreign-derived intangible income, driven by our international business mix and stock-based compensation deduction. Finally, regarding capital expenditures, we continue to plan for capital expenditures in the range of $0.6 billion to $0.8 billion as we further build out our manufacturing and general company infrastructure globally.

對於研發和 SG&A，我們繼續預計全年支出約為 40 億美元，這主要得益於我們成熟的開發組合和公司在全球的擴張。根據現行稅法，我們繼續預計我們 2022 年的稅率將在十幾歲左右，這是由於我們的國際業務組合和基於股票的薪酬扣除推動了來自外國的無形收入的好處。最後，在資本支出方面，隨著我們進一步在全球範圍內建設製造和一般公司基礎設施，我們將繼續規劃 6 億至 8 億美元的資本支出。

As this is the last earnings call for me as CFO of Moderna, I would like to take the opportunity to welcome Jorge Gomez, who's well qualified to lead Moderna in the next stage of its development. I would also like to recognize my own team and my colleagues for our success in ramping up a global commercial company and contributing to taming the pandemic. I have great confidence in the company's ability to fully realize the vast potential of its mRNA technology platform against the many remaining unmet medical needs.

由於這是我作為 Moderna 首席財務官的最後一次財報電話會議，我想藉此機會歡迎 Jorge Gomez，他完全有資格領導 Moderna 下一階段的發展。我還要感謝我自己的團隊和我的同事們，他們成功地發展了一家全球商業公司並為應對這一流行病做出了貢獻。我對公司充分實現其 mRNA 技術平台的巨大潛力以應對許多未滿足的醫療需求的能力充滿信心。

This concludes my remarks concerning the financial performance, and I would like to turn the call back over to Stephane.

我對財務業績的評論到此結束，我想將電話轉回給斯蒂芬。

Thank you, David, for that review of the quarter and those kind of words. More importantly, I would like to thank you for agreeing to come out of retirement in the spring of 2020 to help us scale Moderna at an unprecedented speed from an early-stage development U.S.-centric company to a commercial, global company. I am very grateful for you agreeing to come out of retirement to help us. Your work to get us to this point was crucial. You built a strong team and robust business processes. Thank you for also agreeing to stay on as a consultant as we transition to your successor. And so I want to wish you and your wife well in the next phase of your life.

謝謝你，大衛，對本季度的回顧和那些話。更重要的是，我要感謝您同意在 2020 年春季退休，幫助我們以前所未有的速度將 Moderna 從一家以美國為中心的早期發展公司發展為一家商業化的全球公司。我非常感謝您同意退休來幫助我們。你讓我們走到這一步的工作至關重要。您建立了強大的團隊和強大的業務流程。感謝您在我們過渡到您的繼任者時同意繼續擔任顧問。所以我想祝你和你的妻子在你生命的下一個階段一切順利。

As many of you know, we announced that Jorge Gomez will join us as Chief Financial Officer, effective next Monday, May 9. Jorge brings with him experience in the capacity of CFO for global health care organizations, which are Dentsply and Cardinal health. Jorge has the same kind of high-quality finance trading as David as a General Motor finance alumni. He has a broad set of international experiences in addition to having been CFO of publicly-traded companies.

眾所周知，我們宣布豪爾赫·戈麥斯 (Jorge Gomez) 將於 5 月 9 日下週一加入我們擔任首席財務官。豪爾赫 (Jorge) 帶來了在全球醫療保健組織（包括登士柏和 Cardinal health）擔任首席財務官的經驗。 Jorge 作為通用汽車金融校友，擁有與 David 一樣的優質金融交易。除了擔任上市公司的首席財務官外，他還擁有廣泛的國際經驗。

I would also like to welcome Arpa Garay, who is joining us from Merck at the end of this month as our Chief Commercial Officer. She was a member of Merck Executive Committee where she most recently served as Head of Marketing. Arpa also has a very impressive background and multiple experiences in both sales and marketing. I look forward to partnering with these 2 leaders to continue to scale rapidly Moderna.

我還要歡迎 Arpa Garay，他將於本月底從默克公司加入我們，擔任我們的首席商務官。她是默克執行委員會的成員，最近擔任營銷主管。 Arpa 在銷售和營銷方面也有非常令人印象深刻的背景和豐富的經驗。我期待與這兩位領導者合作，繼續快速擴展 Moderna。

Before moving to Q&A, I would like to review with you our 2022 priorities. Priority number one, to execute on the $21 billion of signed APAs and to prepare for a successful fall 2022 booster season.

在進行問答之前，我想與您一起回顧一下我們 2022 年的優先事項。第一要務是執行價值 210 億美元的 APA，並為成功的 2022 年秋季助推賽季做準備。

Priority number two, to execute on our 4 Phase III vaccine programs, an Omicron COVID-19 bivalent booster, flu booster, RSV booster and CMV prime series vaccine, which could lead to 3 respiratory commercial launches over the next 2 to 3 years.

第二個優先事項，執行我們的 4 個 III 期疫苗計劃，即 Omicron COVID-19 二價加強劑、流感加強劑、RSV 加強劑和 CMV 主要係列疫苗，這可能會在未來 2 至 3 年內推出 3 次呼吸系統商業啟動。

Priority number three, to expand beyond infectious disease vaccine into therapeutics and share proof-of-concept with for PA, MMA and PCV programs.

第三個優先事項，從傳染病疫苗擴展到治療，並與 PA、MMA 和 PCV 項目共享概念驗證。

Priority number four, to bring forward more M&A candidates into clinical development.

優先事項四，將更多併購候選人帶入臨床開發。

And last but not least, priority number five, to continue to expand our mRNA platform, so the possibility of mRNA impact to patients continues to increase over time.

最後但同樣重要的是，優先事項五，繼續擴展我們的 mRNA 平台，因此 mRNA 對患者產生影響的可能性會隨著時間的推移而不斷增加。

I also wanted to remind people of our upcoming events this year, (inaudible) in just 2 weeks on May 17. We'll also host our typical annual R&D Day in September and first ESG Day in November.

我還想提醒人們我們今年即將舉行的活動，（聽不清）在 5 月 17 日的短短兩週內。我們還將在 9 月舉辦典型的年度研發日，並在 11 月舉辦第一個 ESG 日。

While we have had a profound impact on humanity over the last 2 years, we believe that what is ahead of us to help protect and treat hundreds of millions of people is even more exciting. We'll continue to execute on our mission, and we thank you for your support. This is just the beginning.

儘管我們在過去 2 年中對人類產生了深遠的影響，但我們相信，在我們面前幫助保護和治療數億人的事情更加令人興奮。我們將繼續執行我們的使命，感謝您的支持。這僅僅是開始。

Operator, we'll be happy to take questions now.

接線員，我們現在很樂意回答問題。

(Operator Instructions) Our first question comes from Salveen Richter with Goldman Sachs.

（操作員說明）我們的第一個問題來自高盛的 Salveen Richter。

And David, it's been a pleasure working with you. Two questions for me. One is for COVID, based on what's known right now, what regimen as you think about dosing in candidate do you have the most confidence on for annual boosting as you look to in 2023 and beyond?

大衛，很高興與您合作。我有兩個問題。一個是針對 COVID 的，根據目前已知的情況，當您考慮到 2023 年及以後的年度提升時，您對候選人的給藥方案最有信心嗎？

And then secondly, just given your balance sheet and the -- as you look to kind of entering an endemic phase here, how are you thinking about later stage BD and M&A to bolster the revenue line?

其次，考慮到您的資產負債表和 - 當您希望在這裡進入一個流行階段時，您如何考慮後期階段的 BD 和併購以支持收入線？

Thank you, Salveen, it's Stephen. So first, on the COVID booster and what we perceive. As of today, subject to data and obviously collaborating with regulators, we are, as I said, most excited about our bivalent vaccine platform and including Omicron as the now dominant variant and family of subvariants that are infecting people today. Our objective, just like with our bivalent 211 booster data that I presented today, is to provide at least 6 months of protection from that.

謝謝你，Salveen，我是斯蒂芬。首先，關於 COVID 助推器和我們的感知。截至今天，根據數據並顯然與監管機構合作，正如我所說，我們對我們的二價疫苗平台感到最興奮，並將 Omicron 作為目前感染人們的主要變體和亞變體家族。我們的目標，就像我今天展示的二價 211 助推器數據一樣，是提供至少 6 個月的保護。

And because we think this will be a seasonal vaccine, it will be very similar to what people are used to from a food perspective. Meaning in the Northern Hemisphere, you get boosted in the October time horizon, and that would cover you well through the early part of spring when transmission will subside. And so provided that we are able to provide that duration of protection as we've demonstrated already with the 211, we actually think then that means a seasonal annual booster in the fall that would cover people for the year. And as I said, we think it will be the bivalent Omicron containing booster for this year.

而且因為我們認為這將是一種季節性疫苗，所以從食物的角度來看，它與人們習慣的非常相似。這意味著在北半球，你會在 10 月的時間範圍內得到提升，這將在春季早期傳播消退時很好地覆蓋你。因此，只要我們能夠提供如我們已經在 211 中展示的那樣的保護期限，我們實際上認為這意味著秋季的季節性年度助推器將覆蓋全年的人員。正如我所說，我們認為它將是今年包含二價 Omicron 的助推器。

For 2023 plus, we would expect to continue to update the bivalent platform to reflect the then dominant or then at-risk circulating strains of the variant. So it maybe Omicron this year. It may be Omicron again next year or it may be something new.

對於 2023 年以後，我們預計將繼續更新二價平台，以反映該變體當時占主導地位或處於危險中的循環菌株。所以今年可能是 Omicron。明年可能又是 Omicron，也可能是新事物。

Thanks, Stephen. It's Salveen, it's Stephane. So as you know, in term of capital allocation, our priority #1 is to invest in the business. We believe we have this really unique platform that is very different from typical pharma companies or biotech companies where we have an ability to scale very quickly. As we discussed today, we are actively preparing the pivotal studies and the launch of 4 programs in Phase III, as we discussed. As you know, there's a lot of program in Phase II. And I think there's around 30 vaccines in development today.

謝謝，斯蒂芬。是 Salveen，是 Stephane。如您所知，在資本配置方面，我們的首要任務是投資業務。我們相信我們擁有這個真正獨特的平台，與我們能夠快速擴展的典型製藥公司或生物技術公司截然不同。正如我們今天所討論的，正如我們所討論的，我們正在積極準備第三階段的關鍵研究和啟動 4 個項目。如您所知，第二階段有很多計劃。我認為今天大約有 30 種疫苗正在開發中。

And Stephen has showed you today that we believe we have built for our platform and all our investment in digital and a great team, we have the ability in around 12 months to go from opening an IND in vaccine to starting the Phase III. So I think where the pipeline is and where it's going to be 12 months, 24 months from now, that is really exciting.

斯蒂芬今天向您展示了我們相信我們已經為我們的平台以及我們對數字化和優秀團隊的所有投資建立了一個偉大的團隊，我們有能力在大約 12 個月內從打開疫苗 IND 到開始第三階段。所以我認為管道在哪裡，以及從現在開始的 12 個月、24 個月後將在哪裡，這真的很令人興奮。

And then there's therapeutics. We always get a question around COVID-19 for obvious reason. But as we've said in our remarks, this year will be very exciting around therapeutics. We have 2 rare genetic disease programs that are well recruiting, as Stephen described, for which we are eager when we have it, to share data with you. And assuming this is positive, we will do more in rare genetic disease.

然後是治療方法。出於顯而易見的原因，我們總是會收到有關 COVID-19 的問題。但正如我們在評論中所說，今年在治療方面將非常令人興奮。正如斯蒂芬所描述的，我們有 2 個正在招募的罕見遺傳疾病項目，我們渴望在擁有這些項目時與您分享數據。假設這是積極的，我們將在罕見遺傳病方面做得更多。

As you recall, because you've been following the company for a long time, we started with a few infectious vaccines and as we got more confirmation that the technology was working in human and more recently, more capital, we had a very unprecedented acceleration of our infectious disease vaccine. Well, we plan to do the same in rare genetic disease if we get positive clinical data and in this personal cancer vaccine. And as you know, they are -- as Stephen said, more cancer programs, autoimmune programs. And also quite exciting to work with our partner, Vertex, towards getting, following the application, the CF mRNA candidate into the clinic.

正如你所記得的，因為你已經關注公司很長時間了，我們從一些傳染性疫苗開始，隨著我們越來越多地確認這項技術在人類身上發揮作用，而且最近有更多資金，我們獲得了前所未有的加速我們的傳染病疫苗。好吧，如果我們獲得積極的臨床數據和這種個人癌症疫苗，我們計劃在罕見的遺傳病中做同樣的事情。正如你所知，它們是——正如斯蒂芬所說，更多的癌症項目、自身免疫項目。與我們的合作夥伴 Vertex 合作，在申請後將 CF mRNA 候選者帶入臨床也非常令人興奮。

In term of M&A, I can tell you, our teams have never been as busy. They are looking at a lot of opportunities literally across the world, across therapeutic area, but also technologies. And so we will not be shy to invest, to expand the platform, have [full] technology, full products, and that's really where we are in term of M&A. So more to come when things get finalized and signed.

在併購方面，我可以告訴你，我們的團隊從未像現在這樣忙碌。他們正在世界各地尋找大量機會，跨越治療領域，也包括技術。所以我們不會羞於投資，擴大平台，擁有[完整的]技術，完整的產品，這就是我們在併購方面真正所處的位置。當事情最終確定和簽署時，還有更多的事情發生。

And as you know, the third bucket of our priority is in terms of balance sheet, is returning shareholders to capital via share buyback. And so this, as David said, we'll continue to buy back share at attractive prices. And we'll continue to have a dialogue with the Board as to what should we do after the current plan, if needed. But now, we're all focused on executing the current plan. Thank you.

如您所知，我們的第三個優先事項是資產負債表，即通過股票回購將股東返還資本。因此，正如大衛所說，我們將繼續以有吸引力的價格回購股票。如果需要，我們將繼續與董事會就當前計劃之後我們應該做什麼進行對話。但是現在，我們都專注於執行當前的計劃。謝謝你。

Our next question comes from Matthew Harrison with Morgan Stanley.

我們的下一個問題來自摩根士丹利的 Matthew Harrison。

Great. I guess 2 for me. So first, David, could you just comment a little bit more on the upside and downside levers to COVID revenues this year? And in particular, what would be the features that would not allow COVAX to accept the deliveries? Or what should we be looking out for to understand that?

偉大的。我猜2對我來說。那麼首先，大衛，您能否就今年 COVID 收入的上行和下行槓桿多發表一些評論？特別是，哪些功能不允許 COVAX 接受交付？或者我們應該注意什麼來理解這一點？

And then secondly, just on flu, could you maybe give some updated comments on where you are in terms of regulatory discussions? It sounds like it's not clear yet whether or not you're going to need a full efficacy study for approval. And so I'm just wondering where those discussions are and when you think you'll be ready to give people a clearer picture on what the outlook is for the flu program.

其次，就流感而言，您能否就您在監管討論方面的情況發表一些最新評論？聽起來尚不清楚您是否需要進行全面的功效研究才能獲得批准。所以我只是想知道這些討論在哪裡，以及你認為你何時準備好讓人們更清楚地了解流感計劃的前景。

Sure. So on the first one, in terms of the outlook for sales in 2022, I think the most important point is COVAX had an option for additional doses in 2022, which they chose not to exercise. So that's impacted the outlook. We formally were reporting options that could be taken up. That's been taken off the table as they didn't exercise.

當然。所以在第一個方面，就 2022 年的銷售前景而言，我認為最重要的一點是 COVAX 可以選擇在 2022 年增加劑量，他們選擇不行使。所以這影響了前景。我們正式報告了可以採用的選項。由於他們沒有鍛煉，因此已將其從表中刪除。

And what we see is, in our plans in the $21 billion, there continue to be some volume for COVAX. They are actually the consolidator of demand from the countries. So what they need to do is get the confirmed requirements from each country and then that becomes a confirmed order to the company. And notwithstanding having contracts, there's still that process they have to go through. So that's why we want to flag there's some level of uncertainty associated with the timing of that demand that we're reflecting in the APAs.

我們看到的是，在我們 210 億美元的計劃中，COVAX 的交易量仍然很大。他們實際上是各國需求的整合者。所以他們需要做的是從每個國家得到確認的要求，然後這成為給公司的確認訂單。儘管有合同，但他們仍然必須經歷這個過程。這就是為什麼我們要指出與我們在 APA 中反映的需求時間相關的某種程度的不確定性。

And then, of course, we have, as we've said before, a number of negotiations and discussions going on with other countries around the world as we look forward to the fall season and look forward to the variant booster offerings that are making their way through the approval process. So likewise, that presents some potential for additional sales that are not presently in the APA count for this year.

然後，當然，正如我們之前所說，我們正在與世界其他國家進行一些談判和討論，因為我們期待秋季並期待正在製作他們的變體助推器產品通過審批程序的方式。同樣，這也帶來了一些額外的銷售潛力，這些銷售目前不在今年的 APA 計算中。

Thanks. This is Stephen, Matthew. So on the question of flu and where we are, we have been consulting with regulatory agencies globally, as you might imagine, around a path forward for our mRNA-1010 program as there are issued guidance around accelerated approval that are still open. At the end of the day, we still believe that there's a potential path towards an accelerated approval at least in some markets with our mRNA-1010 program using a safety and immunogenicity endpoint as has been previously discussed.

謝謝。這是斯蒂芬，馬修。因此，關於流感問題以及我們所處的位置，正如您所想像的那樣，我們一直在與全球監管機構協商，圍繞我們的 mRNA-1010 計劃的前進道路，因為有關加速批准的已發布指南仍然開放。歸根結底，我們仍然相信，至少在某些市場上，我們的 mRNA-1010 計劃使用安全性和免疫原性終點，至少在某些市場上存在加速批准的潛在途徑，如前所述。

At the end of the day, that will be a review matter, and we'll have to generate that data and have conversations on the back of that data with regulators as a path forward. But even if we do move forward with accelerated approval, which is the study that we're starting, the Q2 Phase III study that we're talking about starting this quarter. Even if we do move forward on the back of that, we will have an obligation even under accelerated approval to demonstrate efficacy at some point in a follow-on study to move from accelerated to full approval.

歸根結底，這將是一個審查問題，我們必須生成這些數據，並在這些數據的背後與監管機構進行對話，作為前進的道路。但即使我們確實推進了加速批准，這是我們正在開始的研究，我們正在談論從本季度開始的第二季度第三階段研究。即使我們確實在此基礎上取得進展，即使在加速批准下，我們也有義務在後續研究中的某個時間點證明從加速批准到完全批准的有效性。

And so because we're certain of that need at some point, we are also planning to start a Phase III efficacy study, which will then be conducted perhaps in the Northern Hemisphere winter, this coming fall. And we also announced data plans for that.

因此，由於我們在某個時候確定了這種需求，我們還計劃開始一項 III 期療效研究，然後可能在即將到來的秋天的北半球冬季進行。我們還為此宣布了數據計劃。

And what that would do is, we would hope, we'd find a path forward for both the accelerated approval, but also rapidly being able to move that to a full approval on the back of that efficacy result. Now for some reason, the accelerated approval is not available in some markets or all markets, we would instead go directly to full approval with a very short latency given the timing of those 2 studies.

我們希望這樣做會為加速批准找到一條前進的道路，同時也能夠在該療效結果的基礎上迅速將其推向全面批准。現在由於某種原因，加速批准在某些市場或所有市場都不可用，鑑於這兩項研究的時間安排，我們將直接以非常短的延遲直接獲得完全批准。

Our next question comes from Gena Wang with Barclays.

我們的下一個問題來自巴克萊銀行的 Gena Wang。

Congrats on the strong quarter. And David, we will miss you. I have a few questions regarding the revenues. David, you mentioned that second half this year will be higher than the first half. Since first quarter, we already delivered $5.9 billion revenues. Should we expect less than $4.5 billion for the second quarter this year?

祝賀強勁的季度。大衛，我們會想念你的。我有幾個關於收入的問題。大衛，你提到今年下半年會比上半年高。自第一季度以來，我們已經實現了 59 億美元的收入。我們是否應該預計今年第二季度不到 45 億美元？

And then my second question is regarding the ex-U.S. $5 billion revenue. What is the breakdown between you and the rest of the world?

然後我的第二個問題是關於前美國的。 50億美元的收入。你和世界其他地方的分歧是什麼？

And the third question is regarding the prices for U.S., EU and the rest of the world. And where do you see these prices change for the remaining of 2022 and also 2023?

第三個問題是關於美國、歐盟和世界其他地區的價格。您認為 2022 年剩餘時間和 2023 年這些價格會發生什麼變化？

Okay. Good. So I'll try to cover them all. And if I miss one, come back to it. So in terms of -- first of all, maybe I'll start at the end on pricing. We previously disclosed the ranges of pricing that we had in the contracts last year. And what you see is that pricing has continued as we contracted for 2021. So really, no change on the price across the various customers. It's really net prices being impacted, as I mentioned, by the mix of customers where we have our COVAX sales at the very lowest price offer. Whereas the other countries, the developed countries, we have varying higher prices.

好的。好的。因此，我將嘗試涵蓋所有內容。如果我錯過了一個，請回到它。所以就 - 首先，也許我會從定價開始。我們之前披露了去年合同中的定價範圍。你所看到的是，隨著我們 2021 年的合同，定價仍在繼續。所以說真的，不同客戶的價格沒有變化。正如我所提到的，淨價格確實受到了我們以最低價格提供 COVAX 銷售的客戶組合的影響。而其他國家，發達國家，我們有不同的更高的價格。

So those continue. We haven't commented on pricing for beyond 2022. But certainly, I think it's fair to assume that, to the extent that the market moves to a private market, typically, you see higher prices and driving markets based on the needs of the market as opposed to when you're addressing the government-acquired product for -- in this pandemic context. So that's one.

所以那些繼續。我們沒有對 2022 年以後的定價發表評論。但是，我認為可以公平地假設，在市場轉向私人市場的情況下，通常情況下，您會看到更高的價格並根據市場需求推動市場而不是在這種大流行背景下解決政府購買的產品時。所以這是一個。

Secondly, in terms of the 2022 outlook, I think you got it right. So basically, first of all, I think it would be a mistake for us to move into quarter-by-quarter accounting of where we see the demand given the variability of this pandemic. But what we see with the $21 billion of signed APAs, we mentioned last quarter and it's the same this quarter, that $21 billion we think will be somewhat higher second half sales than first half. And as you correctly pointed out, the math would then point to the second quarter being likely the lowest that we'll see throughout this year. So I think your thinking on that is right.

其次，就 2022 年的前景而言，我認為你是對的。因此，基本上，首先，我認為考慮到這種流行病的多變性，我們按季度計算需求量是錯誤的。但是，我們在上季度提到的 210 億美元簽署的 APA 中看到，本季度也是如此，我們認為 210 億美元的下半年銷售額將略高於上半年。正如您正確指出的那樣，數學將表明第二季度可能是我們今年全年看到的最低季度。所以我認為你的想法是對的。

And sorry, the third point was?

抱歉，第三點是？

Third point -- that's very helpful. The third question is ex-U.S. $5 billion revenue, what is the breakdown between Europe and the rest of the world?

第三點——這很有幫助。第三個問題是前美國50 億美元的收入，歐洲與世界其他地區之間的細分是什麼？

Yes. So we had -- it was a pretty broad spread. I don't have top-of-mind with specific quantities by country or region, but it was a pretty a broad spread of demand if you look across the world in the first quarter.

是的。所以我們有 - 這是一個相當廣泛的傳播。我不知道按國家或地區劃分的具體數量，但如果你在第一季度放眼全球，這是一個相當廣泛的需求分佈。

Yes. And maybe just to add, Gena, it's Stephane. On the pricing, as David said, has moved into pandemic. As we've been saying, we have to discuss with payers as part of kind of health economics and value of products as it's done for every pharmaceutical product, especially in the U.S. And as you might be aware, CMS has already communicated that for fiscal year 2023, which starts in October 2022, the reimbursement for COVID-19 vaccine is going to be $60. Thank you.

是的。也許只是補充一下，Gena，它是 Stephane。正如大衛所說，定價已經進入大流行。正如我們一直在說的那樣，我們必須與付款人討論作為健康經濟學和產品價值的一部分，因為它對每一種藥品都是如此，特別是在美國。正如你可能知道的那樣，CMS 已經就財政問題進行了溝通從 2022 年 10 月開始的 2023 年，COVID-19 疫苗的報銷將是 60 美元。謝謝你。

Our next question comes from Michael Yee with Jefferies.

我們的下一個問題來自 Jefferies 的 Michael Yee。

I have to ask the last question to David before he gets to go back and then a question for Stephen on the pipeline. I'm going back to the question around the guidance. Can you maybe help us quantify the exposure to COVAX? There was an article I guess talking about some of that recently in the press. And I think that's part of what your APA commentary out today is, I'm sure. Are you saying that, that's partly in the $21 billion, but then offset by potential U.S.A. orders that could come later this year? So maybe you could just talk about that dynamic a bit?

我必須在大衛回去之前問他最後一個問題，然後問斯蒂芬的問題。我將回到圍繞指導的問題。您能否幫助我們量化對 COVAX 的接觸？我猜最近在媒體上有一篇文章談到了其中的一些內容。我認為這就是您今天發表的 APA 評論的一部分，我敢肯定。你是說，這部分是 210 億美元，但隨後被今年晚些時候可能到來的美國潛在訂單所抵消？所以也許你可以談談那個動態？

And then a question for Stephen is, again, definitely excited about propionic acidemia. Can you just rightsize your expectations because it's 5 patients but at the lowest dose? So is that a therapeutic dose you would expect to see biomarker changes? Maybe just talk a little bit about that.

然後斯蒂芬的一個問題是，再一次，對丙酸血症非常興奮。您能否調整您的期望，因為它是 5 名患者，但劑量最低？那麼這是您期望看到生物標誌物變化的治療劑量嗎？也許只是談談這一點。

Sure. So yes, so I'm not sure I have too much to add in terms of the color as to the outlook for the balance of the year. Certainly, again, the $21 billion, we don't, right now, have included any contracts as a result of additional U.S. business, which we think is quite likely we certainly believe there's a recognition of the need for boosters in the U.S., and the dialogue is quite active. That's also true around the world with our customers in other countries and regions.

當然。所以，是的，所以我不確定我在顏色方面有太多要補充的東西，就今年餘額的前景而言。當然，再一次，210 億美元，我們現在不包括由於額外的美國業務而產生的任何合同，我們認為這很可能我們當然相信美國需要助推器，並且對話相當活躍。世界各地的其他國家和地區的客戶也是如此。

And then we wanted to be clear that in the case of COVAX, which is as we've said before, the lowest priced business in the portfolio, but we have confirmed contracts there in place. And we wanted to flag that they are, as I said, a consolidator of underlying demand. And they continue to work through in those developing markets what is exactly that demand picture and what is the timing of it and the ability of those countries to absorb the product that they're receiving. So we want to flag that.

然後我們想明確一點，就 COVAX 而言，正如我們之前所說，它是投資組合中價格最低的業務，但我們已經確認了那裡的合同。正如我所說，我們想指出它們是潛在需求的整合者。他們繼續在這些發展中市場研究需求情況的確切內容，時間安排以及這些國家吸收他們收到的產品的能力。所以我們要標記它。

Quite frankly, if you ask me, should this be an issue of big concern in terms of the total outlook, I would tell you I would put it as quite modest. But we're trying to give some sense as to the range of outcomes in terms of this information.

坦率地說，如果你問我，如果就總體前景而言，這是一個值得關注的問題，我會告訴你，我會說得相當謙虛。但我們正試圖就這些信息的結果範圍提供一些意義。

Thank you, Michael. So look, you point to the most important things, I'll say, which is this [enrollment remains] a small number of patients. It's a rare disease. And as you said, we're looking now in Cohort 1 and Cohort 2 at our lowest dose levels, and we're continuing to enroll. And I would expect, as is appropriate for a Phase I study where we are doing dose finding, Phase I/II, that we will continue to enroll and explore a range of doses, including potentially higher doses in a Cohort 3.

謝謝你，邁克爾。所以看，你指出最重要的事情，我會說，這是[登記仍然]少數患者。這是一種罕見的疾病。正如你所說，我們現在正在尋找最低劑量水平的隊列 1 和隊列 2，並且我們正在繼續註冊。我希望，正如我們正在進行劑量發現的 I/II 期 I 期研究一樣，我們將繼續招募和探索一系列劑量，包括在隊列 3 中可能更高的劑量。

Now that said, we will have a body of data building. As we said, we've got 5 participants who moved into the open-label extension. One has already -- at least one has already been approaching approximately a year on drug, a total of 75 doses. And so as you look -- as you look at that body of data, it will start to provide potentially an early signal. And I think in that sense, the things that I will personally be looking at, I think we'll be focused on, first and foremost, it's clinical end points. It is the clinical endpoints that matter most to these patients, obviously.

話雖如此，我們將擁有一個數據構建體。正如我們所說，我們有 5 名參與者進入了開放標籤擴展。一個已經 - 至少一個已經接近大約一年的藥物，總共 75 劑。因此，當您查看時-當您查看該數據體時，它將開始提供潛在的早期信號。我認為從這個意義上說，我個人將關注的事情，我認為我們將首先關注臨床終點。顯然，對這些患者最重要的是臨床終點。

We are developing the medicine to try and prevent the sequela of disease. And so obviously, that includes things like metabolic decompensation events, hospitalization, other interventions, other progression signs of their disease. And importantly, that's something you really only measure over time as opposed to a biomarker, which I'll get to in a second. You really need to see about what that looks like over time. Now the benefit of where we will be this year is that we will have a reasonably large amount of time for these small number of patients on drug. And so that's something that we'll be focused intensely on. But again, it's [small in] and that we'll be looking at.

我們正在開發藥物以嘗試預防疾病的後遺症。很明顯，這包括代謝失代償事件、住院治療、其他干預措施、疾病的其他進展跡象。重要的是，這是你真正只能隨時間測量的東西，而不是生物標誌物，我稍後會談到。你真的需要看看隨著時間的推移會是什麼樣子。現在，我們今年所處的位置的好處是，我們將有相當多的時間為這些少數藥物患者服務。所以這是我們將重點關注的事情。但同樣，它[小]，我們將關注。

When it comes to biomarkers, we're looking at a range of biomarkers. It's important to note there are no validated biomarkers in this disease. It's not even guaranteed that we discover a validated biomarker in this disease. But obviously, it will be helpful as an evidence of pharmacology and the potential for benefit in clinical endpoints that we do try and measure those.

當談到生物標誌物時，我們正在研究一系列生物標誌物。重要的是要注意在這種疾病中沒有經過驗證的生物標誌物。甚至不能保證我們會在這種疾病中發現一種經過驗證的生物標誌物。但很明顯，這將有助於作為藥理學的證據以及我們確實嘗試和測量這些臨床終點的潛在益處。

And so we're looking at a range of biomarkers. We've described many of the ones that are associated with the disease. And that will be other data that we will have as we pull together these first couple of cohorts and we have a cogent story to tell around them. And the balance of the clinical endpoints and the biomarker data together will help us decide whether we've found the correct dose to move forward or whether more work is needed to find a more optimal dose for this patient population.

因此，我們正在研究一系列生物標誌物。我們已經描述了許多與該疾病相關的疾病。這將是我們將前幾個隊列聚集在一起時將擁有的其他數據，並且我們圍繞他們講述一個令人信服的故事。臨床終點和生物標誌物數據的平衡將幫助我們確定我們是否找到了正確的劑量以繼續前進，或者是否需要更多的工作來為該患者群體找到更優化的劑量。

I think the encouraging thing is, as we stand today, is that we do know there are patients that have been on drug for quite a long period of time. And that longitudinal experience allows us to look at clinical endpoints and also gives us some good indication, hopefully, where we're going to be on safety, which is obviously essential for this medicine to move forward.

我認為令人鼓舞的是，正如我們今天所站的那樣，我們確實知道有些患者已經服用了很長時間的藥物。這種縱向經驗使我們能夠查看臨床終點，也為我們提供了一些很好的指示，希望我們將處於安全狀態，這顯然對於這種藥物的發展至關重要。

Our next question comes from Tyler Van Buren with Cowen.

我們的下一個問題來自 Tyler Van Buren 和 Cowen。

So the Ontario study provides some interesting initial evidence that the fourth dose is beneficial. And you mentioned the populations that should get the fourth dose. So how big in aggregate is this population in total? What percent of the U.S. and global population do these patient groups comprise?

因此，安大略省的研究提供了一些有趣的初步證據，證明第四劑是有益的。你提到了應該接種第四劑的人群。那麼這個人口總共有多少呢？這些患者群體占美國和全球人口的百分比是多少？

And the second question was just a follow-up on prior reflections to make sure that I'm clear. Did you say that the average selling price per Spikevax dose in 2022 will be lower than '21 due to COVAX orders? And does this not account for a potential increased price from future U.S. orders? And could these offset that decline in ASP, especially if you sell a sizable portion of doses at year-end at that $60 per dose price I believe you just mentioned per the CMS announcement?

第二個問題只是對先前思考的跟進，以確保我清楚。您是否說由於 COVAX 訂單，2022 年每劑 Spikevax 的平均售價將低於 21 年？這難道不能說明未來美國訂單的潛在價格上漲嗎？這些能否抵消 ASP 的下降，特別是如果你在年底以每劑 60 美元的價格出售相當大一部分劑量，我相信你剛剛在 CMS 公告中提到過？

Very good. Go ahead. Yes.

很好。前進。是的。

Sorry. Go ahead, David, you take the first one, and then I'll comment on the...

對不起。繼續，大衛，你拿第一個，然後我會評論...

Yes. So if I track that, in terms of pricing, that's correct. We have had and we continue to have, based on the customer mix this year versus last year, we had indicated that we'll have a year-over-year decline in the average price of product being sold when we look at the $21 billion of APAs compared to last year's actual.

是的。因此，如果我在定價方面進行跟踪，那是正確的。根據今年與去年的客戶組合，我們已經並且我們繼續擁有，我們曾表示，當我們查看 210 億美元時，我們所售產品的平均價格將同比下降APA 與去年的實際值相比。

And the key contributor to that decline for the year is, in fact, the inclusion of COVAX volume in the confirmed APAs that we previously were discussing. So that contributes to an average sale price decline. Will that sale price on average in 2022 change from that outlook? Yes. It can to the extent there were change in volume for COVAX, including if it were some -- of the volume were to defer beyond '22 into '23, for example, that would improve your average price calculation.

事實上，今年下降的主要因素是我們之前討論過的已確認的 APA 中包含了 COVAX 交易量。因此，這導致平均銷售價格下降。 2022 年的平均售價是否會與該前景有所不同？是的。它可以在一定程度上 COVAX 的交易量發生變化，包括如果它是一些 - 例如，交易量將超過 22 年推遲到 23 年，這將改善您的平均價格計算。

And then likewise, to the extent which we've indicated, we have an expectation of additional sales of product in 2022 for the fall season, including potentially for private market should that develop. That would then presumably have a favorable impact on the average price. So hopefully, that is clear.

同樣，在我們已經表明的範圍內，我們預計 2022 年秋季的產品銷售會增加，如果這種情況發展，可能會進入私人市場。那麼這可能會對平均價格產生有利影響。所以希望，這很清楚。

And just to comment on the number of individuals who we think at high risk. Clearly, it can change as we see the vaccine -- we've seen with the epidemiology of the virus, as Stephen commented earlier. But just going back to our Vaccines Day earlier, we think that, that high-risk population is somewhere in the range of about 1.7 billion people worldwide.

並且只是評論我們認為處於高風險中的個人數量。顯然，隨著我們看到疫苗，它會發生變化——正如斯蒂芬早些時候評論的那樣，我們已經看到了病毒的流行病學。但回到我們早些時候的疫苗日，我們認為，高危人群在全球約 17 億人的範圍內。

Okay. Congratulations again, David, on your second retirement.

好的。再次祝賀大衛，您第二次退休。

Our next question comes from Cory Kasimov with JPMorgan.

我們的下一個問題來自摩根大通的 Cory Kasimov。

This is Tiffany on for Cory. So as the U.S. government hasn't procured a budget for boosters this fall and if they continue to not place orders, can you walk us through some of the implications of what that privatization potentially means and how the company is thinking about it? You mentioned potentially higher prices, but anything from market research that might suggest demand change or how you're thinking about discounts, et cetera?

這是科里的蒂芙尼。因此，由於美國政府今年秋天還沒有為助推器採購預算，如果他們繼續不下訂單，你能告訴我們私有化可能意味著什麼以及公司是如何考慮的嗎？您提到了潛在的更高價格，但市場研究中可能暗示需求變化或您如何考慮折扣等的任何內容？

Sure. Tiffany, this is Stephane. So indeed, while we are in discussion with the U.S. government, as you would assume is appropriate, we're also working towards assuming that there's no government order or American order for vaccines. We want to make sure we can protect as many Americans as we can with the vaccine. And so with our commercial U.S. team, we're working very diligently, and David and I have spent quite some time in the last weeks and months to make sure that we have all the wholesaler contracts and all the pieces you need to be able to be commercial in the [rational sense] of the world in vaccine.

當然。蒂芙尼，這是斯蒂芬妮。因此，事實上，雖然我們正在與美國政府進行討論，但正如你所認為的那樣，我們也在努力假設沒有政府訂單或美國的疫苗訂單。我們想確保我們可以用疫苗保護盡可能多的美國人。因此，與我們的美國商業團隊一起，我們非常勤奮地工作，大衛和我在過去幾周和幾個月里花費了相當長的時間來確保我們擁有所有批發商合同和你需要的所有部件能夠在疫苗的世界[理性意義上]商業化。

And we have quite a number of executives that are vaccine self-experienced in the U.S. on our team. And so while we hope that the U.S. government, like other countries in the world, will decide to place another like we've done in the past to allow the maximum number people, recruiting people and ensure to get vaccinated, we're getting fully already assuming the day 0 order from the U.S. government, just in case if that happens. That is a 100% private market in the fall, and the company will be ready for that.

我們的團隊中有很多在美國有疫苗經驗的高管。因此，雖然我們希望美國政府像世界上其他國家一樣，決定像我們過去所做的那樣安排另一個，以允許最大數量的人員、招募人員並確保接種疫苗，但我們正在充分已經假設來自美國政府的第 0 天訂單，以防萬一。那是秋季 100% 的私人市場，公司將為此做好準備。

Okay. Great. And then just a second one. So how should we think about operating expenses moving forward and potentially steering away from COVID as a big driver there? Will it be pipeline dependent or something else?

好的。偉大的。然後只是第二個。那麼，我們應該如何考慮向前發展的運營費用以及可能從 COVID 轉向那裡的大驅動力呢？它會依賴於管道還是其他什麼？

Yes, it's a good question. We've tried to give you the indication of the trends for expenses across the business. What I would expect to continue is a very significant investment in R&D as that pipeline progresses and expands. And I would say it shouldn't be surprising if you see -- if you move past 2022 that you'll see a continued increase in the investments in that area, presuming success which we're feeling very good about.

是的，這是個好問題。我們試圖讓您了解整個企業的開支趨勢。隨著管道的進展和擴展，我希望繼續對研發進行非常重大的投資。我想說的是，如果你看到——如果你超過 2022 年，你會看到該領域的投資持續增加，這並不奇怪，假設我們對成功感到非常滿意。

And then in terms of the other considerations, in terms of cost, in terms of SG&A and -- if you look at the business now, we've substantially built out the company, as we've talked about, as a global commercial enterprise. So I think we're while perhaps not precisely there yet, we're largely there in terms of if you look at the structure of the business globally. So that I think you might consider to be more of a steady state. So that would be my initial comments on the thinking on that.

然後在其他考慮方面，在成本方面，在 SG&A 方面，以及 - 如果你現在看業務，正如我們所討論的那樣，我們已經將公司大幅打造為一家全球商業企業.因此，我認為我們雖然可能還不完全在那裡，但如果你看一下全球業務的結構，我們基本上就在那裡。所以我認為你可能會考慮更穩定的狀態。這就是我對此想法的初步評論。

Our next question comes from Geoffrey Meacham with Bank of America.

我們的下一個問題來自美國銀行的 Geoffrey Meacham。

This is Alex [Hammonds] on for Geoff Meacham. So on BD, how do you think about partnerships versus acquisitions? And how large of a deal would you be willing to consider? And then if I may, can you provide your thoughts on the RSV competitive landscape? And any color on time lines for the readout?

這是 Geoff Meacham 的 Alex [Hammonds]。那麼在 BD 上，您如何看待合作與收購？你願意考慮多大的交易？如果可以的話，您能否提供您對 RSV 競爭格局的看法？讀數的時間線上有什麼顏色嗎？

Yes. So this is Stephane. Partnership versus M&A., I think it's really a question of risk and then willingness of sellers to sell, because there needs to be two to tango. And so as we've done from our deal with Metagenomi, whether we do a partnership in terms of licensing for Metagenomi, because we are very excited about the science and the team that we discovered over time and with diligence. We thought at this stage of the generating technology of that company, it was not the best thing for us to do from a risk-adjusted basis to acquire the company.

是的。這就是斯蒂芬。合夥與併購，我認為這實際上是一個風險問題，然後是賣家出售意願的問題，因為需要有兩個來探戈。正如我們從與 Metagenomi 的交易中所做的那樣，無論我們是否在 Metagenomi 的許可方面建立合作夥伴關係，因為我們對隨著時間的推移和勤奮發現的科學和團隊感到非常興奮。我們認為在該公司發電技術的現階段，從風險調整的基礎上收購該公司對我們來說不是最好的事情。

And in terms of M&A, we would be very happy to buy the right company that we really believe will drive value to Moderna on a risk-adjusted basis. In terms of deal size, we're looking at a lot of different things. But again, we are staying very disciplined. We are here to create value, not to do things just for the sake of doing things. As you know, a lot of us have a significant share in the company, and we are already focused on creating value.

在併購方面，我們很樂意購買合適的公司，我們相信這將在風險調整的基礎上為 Moderna 帶來價值。就交易規模而言，我們正在考慮很多不同的事情。但同樣，我們保持非常自律。我們來這裡是為了創造價值，而不是為了做事而做事。如您所知，我們中的許多人在公司中佔有重要份額，並且我們已經專注於創造價值。

So the BD team, as I said, is the most busy they have been in a long time. We're looking at a lot of things literally around the world because the best science is not always in this country. If there's a lot of amazing science in this country, but there's a lot of other smart people around the planet. And we think we modernize infrastructure and capital, actually has a lot of technology that we could partially scale up where there's production teams that have cool science, but not necessarily the right balance sheet and our infrastructure to scale and to maximize patient impact.

因此，正如我所說，BD 團隊是他們很長時間以來最忙碌的。我們正在研究世界各地的很多事情，因為最好的科學並不總是在這個國家。如果這個國家有很多驚人的科學，但地球上有很多其他聰明人。我們認為我們對基礎設施和資本進行了現代化改造，實際上有很多技術可以部分擴大，因為生產團隊擁有很酷的科學，但不一定有正確的資產負債表和我們的基礎設施來擴大規模並最大限度地擴大患者影響。

Stephen, you want to take technology?

斯蒂芬，你想拿技術嗎？

Sure. So on RSV, so first, where we are on the data of our program, 1345, we think the titers, the neutralizing antibody titers, GMTs we've seen, look really strong relative to competitors. And we also feel quite optimistic and positive about our history of generating strong T cell responses against respiratory viruses. And the mRNA platform, in particular, has demonstrated, we think, through the COVID pandemic, pretty remarkable performance relative to more traditional approaches. And so the combination has us optimistic. We ultimately don't need to go demonstrate in a clinical trial that potential benefit. And that's a Phase III study that we're now in and going full speed at.

當然。所以在 RSV 上，首先，在我們的程序數據 1345 上，我們認為滴度，中和抗體滴度，我們看到的 GMT，相對於競爭對手來說看起來非常強大。我們也對我們對呼吸道病毒產生強烈 T 細胞反應的歷史感到非常樂觀和積極。尤其是 mRNA 平台，我們認為，通過 COVID 大流行，與更傳統的方法相比，它的表現相當出色。因此，這種組合讓我們感到樂觀。我們最終不需要在臨床試驗中證明潛在的好處。這是一項我們現在正在全速進行的第三階段研究。

That Phase III study, like our other respiratory virus efficacy studies is a case-driven design. And so at the end of the day, we have to enroll people, vaccinate them and then make sure that we accrue enough cases to conduct the interim and final analysis. That is something that we're trying to make sure we're enrolling in geographies where we expect and anticipate RSV surges.

與我們的其他呼吸道病毒功效研究一樣，該 III 期研究是案例驅動的設計。所以在一天結束時，我們必須招募人員，為他們接種疫苗，然後確保我們積累了足夠的病例來進行中期和最終分析。這是我們正在努力確保我們在我們預期和預期 RSV 激增的地區註冊的事情。

And there have been recent reports from a competitive landscape perspective of others modifying their studies to increase the number of enrolled subjects in their pivotal studies because perhaps they haven't yet hit that rate of case accrual. In some ways, we think that provides us an opportunity to close even more ground because now we're all rapidly working to try and demonstrate the potential of RSV vaccines to help this same older adult population. So it's beyond our control to know when exactly we will have those cases accrued. But obviously, we'll be working hard to make sure that we're as enriched as possible.

從競爭格局的角度來看，最近有報導稱，其他人修改了他們的研究，以增加他們關鍵研究中的註冊受試者數量，因為他們可能還沒有達到這個案例積累率。在某些方面，我們認為這為我們提供了一個關閉更多領域的機會，因為現在我們都在迅速努力嘗試並展示 RSV 疫苗幫助同樣的老年人群的潛力。因此，我們無法確切知道何時會累積這些案件。但顯然，我們將努力確保我們盡可能豐富。

Now from an overall competitive perspective, other than the vaccine -- the freestanding RSV vaccine in older adults, which as I said, we're quite optimistic about the GMT -- T cell response to the platform, we are also studying combos. Because at the end of the day, these are not the only virus -- it's not the only virus affecting these populations.

現在從整體競爭的角度來看，除了疫苗——老年人的獨立 RSV 疫苗，正如我所說，我們對 GMT 非常樂觀——T 細胞對平台的反應，我們也在研究組合。因為歸根結底，這些不是唯一的病毒——它不是影響這些人群的唯一病毒。

And so I'll remind you that we have an RSV flu, COVID combo, which we are going to start a clinical study on, we believe, this year, which would be a combination of all of the 3 most common respiratory pathogens that are impacting older adults. And as I said, a moment ago, we fully enrolled our RSV and human metapneumovirus combination, which I'll remind you, that's in the pediatric population and another important population for RSV, where both of those viruses can lead to morbidity in young children.

所以我要提醒你，我們有一種 RSV 流感和 COVID 組合，我們相信，今年我們將開始一項臨床研究，這將是所有 3 種最常見的呼吸道病原體的組合，它們是影響老年人。正如我剛才所說，我們完全註冊了我們的 RSV 和人類偏肺病毒組合，我會提醒你，這是在兒科人群和 RSV 的另一個重要人群中，這兩種病毒都可能導致幼兒發病.

And so we are continuing down our strategy of making sure that we're not just addressing 1 pathogen, but that we're providing the best potential health intervention. So that includes that combination strategy. And over time, we think as we demonstrate the potential of our platform against any individual virus, the part of the real value we will deliver to health care systems and patients is the ability to do those combinations quickly to reflect the epidemiology, the underlying patient population is different in younger kids than it is in older adults.

因此，我們正在繼續我們的戰略，以確保我們不僅針對一種病原體，而且我們正在提供最好的潛在健康干預措施。這包括組合策略。隨著時間的推移，我們認為，當我們展示我們的平台對抗任何單個病毒的潛力時，我們將為醫療保健系統和患者提供的真正價值的一部分是能夠快速進行這些組合以反映流行病學、潛在患者年幼兒童的人口與老年人不同。

Kevin, we have time for one more question.

凱文，我們有時間再問一個問題。

Okay. Our last question comes from Joseph Stringer with Needham & Company.

好的。我們的最後一個問題來自 Needham & Company 的 Joseph Stringer。

I had one on the rare disease programs. And just curious, you have the PA in MMA and clinical development here in an initial readout in PA. How much is the PA readout? Would that be sort of derisking in terms of bringing additional rare disease programs into the clinic? Has it been more of a -- some of the hurdles and challenges to expanding that area of the pipeline? Is it then more on an indication-specific basis? Or have you been sort of waiting for the initial proof-of-concept readouts to bring more programs into the fold? Or has it been more of influenced by sort of the focus on COVID and potentially headwinds related to the COVID pandemic? Any additional color on that would be helpful.

我有一個關於罕見病項目的。只是好奇，您在 PA 的初始讀數中擁有 MMA 和臨床開發中的 PA。 PA讀數是多少？就將更多的罕見病項目引入臨床而言，這會是一種冒險嗎？擴大管道的那個區域是否更像是一些障礙和挑戰？那麼它是否更多地基於特定適應症？或者您是否一直在等待最初的概念驗證讀數以將更多程序納入其中？還是更多地受到對 COVID 的關注以及與 COVID 大流行相關的潛在不利因素的影響？任何其他顏色都會有所幫助。

Great. Thank you for the question. And it is going to be a mix of all of the factors you listed. So first, let me talk about PA and what that readout means for us as a platform.

偉大的。感謝你的提問。這將是您列出的所有因素的混合。首先，讓我談談 PA 以及該讀數對我們作為一個平台意味著什麼。

So it is our most advanced rare disease platform with an mRNA LNP targeted for those metabolic diseases. And in that sense, MMA and PA, both will provide validation that the technology risk associated with that are addressed. And that would cause us, from a derisk perspective, from a strategy perspective to expand the number of diseases we go into quite quickly there that could use that same technology.

因此，它是我們最先進的罕見病平台，具有針對這些代謝疾病的 mRNA LNP。從這個意義上說，MMA 和 PA 都將驗證與之相關的技術風險已得到解決。從風險的角度來看，從戰略的角度來看，這將導致我們擴大可以使用相同技術的疾病的數量。

We have been waiting for that readout. We haven't sat on our hands though. I'll note that we have a third program, GSD1a with an open IND that, as we've said before, in this slightly -- is in a different lipid nanoparticle system. So we've continued to look at whether other improvements could help. And we'll continue to look at those. But obviously, if we have a very strong signal out of PA, we will be on gating other programs that can benefit from the technology that with NBD risk from the PA program.

我們一直在等待那個讀數。不過，我們還沒有坐在我們的手上。我會注意到我們有第三個程序，GSD1a，它有一個開放的 IND，正如我們之前所說的，在這個稍微 - 是在一個不同的脂質納米粒子系統中。因此，我們繼續研究其他改進是否會有所幫助。我們將繼續研究這些。但很明顯，如果我們從 PA 發出非常強烈的信號，我們將關閉其他可以從 PA 計劃中存在 NBD 風險的技術中受益的計劃。

When it comes to just the challenges of conducting these studies, I'll remind you that these are, unfortunately, very ill children often in these studies and relatively rare diseases. And so yes, it has been difficult throughout the pandemic in an experimental context to bring people in.

當談到進行這些研究的挑戰時，我會提醒你，不幸的是，這些研究中的孩子經常病得很重，而且疾病相對罕見。所以，是的，在整個大流行期間，在實驗環境中很難讓人們參與進來。

And there have been several times during the last 2 years that we have actually taken an active decision with investigators and families not to be enrolling people because, obviously, bringing sick children into hospitals was exposing them to risks around SARS-CoV-2. There are obviously also even more recently in the Omicron surge. Lots of disruption that these institutions have faced as staff and others have become ill, and therefore, we can't connect the studies.

在過去的 2 年中，我們實際上已經多次與調查人員和家屬一起積極決定不招收人，因為很明顯，將生病的兒童送進醫院會使他們面臨 SARS-CoV-2 周圍的風險。顯然還有最近在 Omicron 的激增。隨著工作人員和其他人生病，這些機構面臨著許多破壞，因此，我們無法將這些研究聯繫起來。

We hope that a lot of that is behind us now as we move to an endemic phase for SARS-CoV-2 and that, that will -- that we will really see a pickup in our ability to continue to execute the study. So we're proud of the progress we've made in the last year.

我們希望，隨著我們進入 SARS-CoV-2 的流行階段，現在很多事情都已經過去了，那將會——我們將真正看到我們繼續執行研究的能力有所提高。因此，我們為去年取得的進展感到自豪。

Well, thank you very much for joining us today. And we look forward to meeting a lot of you in person in Boston when we do the R&D day 2 weeks from now. Have a great day. Thanks.

嗯，非常感謝你今天加入我們。我們期待在兩週後的研發日期間在波士頓與你們中的許多人見面。祝你有美好的一天。謝謝。

Ladies and gentlemen, this does conclude today's presentation. You may now disconnect, and have a wonderful day.

女士們，先生們，今天的演講到此結束。您現在可以斷開連接，度過美好的一天。