Q4 2021 Moderna Inc Earnings Call

Good morning, My name is Kevin and I'll be greater today.

Kevin: Good morning, my name is Kevin, and I'll be your operator today. Welcome to Moderna's fourth quarter and full year 2021 earnings call. At this time, all participants are on a listen. Following the formal remarks, we will open the call up for questions. Please be advised that this call is being recorded. At this time, I'd like to turn the call over to Lavina Talukdar, Head of Investor Relations at Moderna. Thank you, Kevin. Good morning, everyone.

Welcome to <unk> during this fourth quarter and full year 2021 earnings call. At this time all participants are in a listen only mode. Following the formal remarks, we will open the call up for questions. Please be advised that this call is being recorded at this time I'd like to turn the call over to Olivia to Luca <unk> head of Investor Relations. Please proceed.

Thank you Kevin.

Lavina Talukdar: And thank you for joining us on today's call to discuss Moderna's fourth quarter and full year 2021 financial results and business updates. You can access the press release we issued this morning, as well as the slides that we'll be reviewing by going to the investor section of our website. On today's call, our Stephane Bancel, our Chief Executive Officer, David Muehne, our Chief Financial Officer.

Everyone and thank you for joining us on today's call to discuss mature in its fourth quarter and full year 2021 financial results and business update you can access the press release, we 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 Stefan bunch L. Our Chief Executive Officer, David Mclean, Our Chief Financial Officer, Stephen Hoge, Our President and Paul Burton, Our Chief Medical Officer.

Lavina Talukdar: Stephen Hoge, our President, and Paul Burton, our Chief Medical Officer. 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 slot two 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 states. With that, I will turn it over to Stephane. Thank you Lavina. Good morning and good afternoon everyone.

Before we begin please note that this conference call will include forward looking statements made Christian went to the Safe Harbor provisions of the private Securities Litigation Reform Act of 1995.

See slide two 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 with that I will turn it over to Keith.

Stefan.

Stephane Bancel: Welcome to our Q4 2021 conference call. Today I will start by a quick business review of Fiscal Year 21 before Paul walks you through some real-world evidence data. Stephen will then review our clinical programs before David presents our financial results. I will then come back to close to share some thoughts about where we are heading.

Thank you Laurie good morning, good afternoon, everyone.

Throughout Q4, when you got Q1 conference call.

Let me start by quick business review of fiscal year 'twenty, one before Paul walks you through some real world evidence data.

Stephen will then review our clinical programs before David presents our financial results.

Well come back to growth to share some thoughts about where we are heading.

We are pleased to report to the $18 5 billion of revenues for fiscal yes, what you don't get one and a GAAP net income of $12 2 billion translating into a GAAP diluted earnings per share of 28 29 billion.

Stephane Bancel: We are pleased to report today $18.5 billion of revenues for fiscal year 2021 and a GAAP net income of $12.2 billion, translating into a GAAP-diluted earnings per share of $28.29 billion, with a cash balance at the end of the year of $17.6 billion. We're not this morning that we have completed, or August, 2021, $1 billion share by back then, which reduced our average checkout during the fourth quarter of the first time in the company history.

With a cash balance at the end of the year of $17 6 billion barrels.

We announced this morning that we have completed August one gigawatt to one $1 billion share buyback plan, which reduced our average share count during the fourth quarter for the first time in company history.

Stephane Bancel: I am very proud of a team's ability to advance, as well as expand with new programs our development pipeline. In respiratory vaccines, for COVID, as you know, we received full PLA approval from the US FDA for SpikeVac. With authorization, for 12 to 17 years old in key markets globally, we are running a 50 microgram dose study in the U.S. for adolescents following discussions with the FDA. We are pleased to report that we have also started to receive authorizations for children aged 6 to 11 years of age being in Australia last week, with more countries expected in the days and weeks to come.

I am very proud of our team's ability to adapt.

As well as expand with new programs our development pipeline.

In respiratory vaccines.

As you know, we would give ford geely, but prove.

For the U S EBITDA phosphate box.

We have authorization for sweat with domestic or key markets globally. We are running a 50 microgram dose studied in the U S for adolescents following discussions with the FDA.

We are pleased to report this revenue started to receive authorization Fox Euro 611 years of age beginning in Australia last week, we've increased expectation the days and weeks to come.

Well. So those are first party best in the Omicron specific vaccine trial, among its about 70% of <unk> nine and.

Stephane Bancel: Also, those are the first participants in the Omicron-specific vaccine trial, mRNA-1273.529. And today we are announcing that we plan to bring mRNA-1273.214, a bivalent vaccine combining the wild-type vaccine, mRNA-1273, and the Omicron vaccine, mRNA-1273.529, into the clinic with a total mass of 50 micrograms, into the clinic. We're very excited that now LSV is in phase 3.

And today, we're announcing that we plan to bring <unk> sweater 70 freed up to windfall bivalent vaccine combining of the wild type vaccine amongst prospective free and the omicron vaccine <unk> 75 to nine into one single dose <unk> into the clinic with total mass or 15 microgram.

We're very excited that now as the phase III.

This is our first vaccine starting to phase III.

Stephane Bancel: This is our third vaccine starting phase 3, and Foroohar, we are waiting for phase 2 data for Amarnie Tentan. As soon as we have them, we will pick those, and we'll initiate phase 3 foroohar, and we will start phase 1 for COVID plus group program, Amarnie Telt7. For latent viruses, CMV is enrolling in Phase 3, EBV and HIV are now in Phase 1, and we are very excited to announce last week that we are adding two new latent virus programs to our development pipeline, one vaccine against HSV and one vaccine against VZV. More latent virus vaccines are in the works in our labs.

And fall through where we think the phase II data for <unk>.

As soon as we have.

We will pick a dose and will initiate a phase III for flu and when we stopped all phase Westfall Kobe Christopher program amounted to 73.

For latent virus CMV is enrolling in phase III you began this JV I'll now in phase one and we're very excited to announce last week that we added two new latent virus program to our development pipeline, one vaccine against HSV and went vaccine against <unk>.

More or less in balance these vaccines are in the works in all apps.

In fact predicts pier and EMEA kind of Clinique <unk> more patients.

Stephane Bancel: We announced a new checkpoint cancer vaccine, mRNA 4359. And Merck has informed us that they are returning the rights to the Keras vaccine. We are evaluating future steps for this program. The company continues to expand at the rapid pace.

We announced the new checkpoint cost of active M&A 40 for if you could go back and look at him from those that we are returning the rights to the carriers vaccine, while evaluating future steps for this program.

Stephane Bancel: We now have one approved medicine, two in-phase free, RSVNCMV, and five in-phase, There's a total of 44 programs. We're deploying Capitore to Axel Wright and expand the pipeline. The company now has 3% team members across the world, with a great culture and 11 commercial subsidiaries across Americas, Europe, and Asia-Pacific. Our $17 billion cash balance at the end of the year is enabling us to scale across research, development, manufacturing, commercial, and GM. With this, let me now turn to Paul.

The company continues to expand at a rapid pace. We have one approved medicine, two week phase III OSB in CMV and firing phase tool.

44 programs.

We are deploying capital to accelerate and expand the pipeline. The company now has 3000 team members across the world with a great culture, and 11 commercial subsidiaries across Americas, Europe , and Asia Pacific All 17 billion the rough cash balance at the end of a year is it anyway.

For you guys to scale across research development manufacturing commercial and Jamie We've maybe thats helpful.

Thank you Stefan and Hello.

Paul Burton: Thank you, Stephane, and hello. Thank you, Stephane. And hello, everyone.

Okay.

Paul Burton: It is almost exactly three months ago that we first heard about the, And today we look back on three months that have seen millions of new cases of COVID-19 infection worldwide due to Omicron, and a death toll that turned out to be almost 20% higher than that seen during the Delta wave. It is clear that SARS-CoV-2 is a virus capable of making very large evolutionary leaps in its structure and function. And while we are hopeful that we are about to enter a period of relative stability in the Northern Hemisphere, we believe firmly that a vaccine booster dose that will be required for the fall of 2022 to provide ongoing protection against this virus.

Thank you Stefan and Hello, everyone. It is almost exactly three months ago that we first heard about the <unk>.

Okay.

Paul.

And today, we look back from three mode that have seen millions of new cases of COVID-19 infection worldwide due to omit truck and a desk toll that turned out to be almost 20% higher than that seen during the depth to wave. It is clear that solids covey too, it's a virus capable of making very large.

Evolutionary leaps in its structure and function.

And while we are hopeful that we are about to enter a period of relative stability in the northern hemisphere. We believe firmly that a vaccine booster dose will be required for the fall of 2022 to provide ongoing protection against this virus.

We have seen measures taken by the United Kingdom recently to offer an additional boost to dose to those higher risk and we believe such measures will become more widespread with governments looking to protect their populations from disease. Later this year and support the health care systems.

Paul Burton: We have seen measures taken by the United Kingdom recently to offer an additional boost to those higher risks. And we believe such measures will become more widespread with governments looking to protect their populations from disease later this year and support their health care system. As always, a huge note of appreciation to the frontline workers, the health care workers who have continued to immunize us and protect us during this pandemic. Their tireless work has saved millions of lives worldwide.

As always a huge note of appreciation to the frontline workers the health care workers.

We have continued to immunize us and protect us during this pandemic.

Tireless work to save millions of lives worldwide.

Yeah.

I am going to review some data today that underpins why we believe an additional boost Shaw will be required certainly by the fall of 2022.

Paul Burton: I'm going to review some data today that underpins why we believe an additional booster shot will be required, certainly by the fall of 2022. First, let me share with you some data from a study of almost 440,000 individuals in the United States Veterans Administration Database, looking at the effectiveness of mRNA-1273 spike vaccine, used in the primary series vaccination set. As we know, the mRNA vaccines are extremely safe and effective, and the data here show the exceptional effectiveness of mRNA-1273.

First let me share with you some data from a study of almost 440000 individuals in the United States Veterans Administration database looking at the effectiveness of mrna 12, 73 spiked VIX.

And the primary series vaccination setting.

As we know the mrna vaccines extremely safe and effective and the data here shows the exceptional effectiveness of mrna 12 73.

Paul Burton: In this well-powered and prospectively designed comparative effectiveness study, mRNA-1273 significantly reduced the risk of COVID-19 infection and hospitalization compared to BNT162b2. These data are reassuring and continue to underpin the strong global confidence that governments, healthcare systems and individuals have in mRNA COVID-19 vaccines and mRNA-1273. Indeed, an example of that is the very recent announcement by the CDC of British Columbia for the preferential use of the Moderna vaccine in anyone over 12 years of age living with immunocompromised. A similar pattern of results is seen from real world effectiveness studies in the United Kingdom.

And this well powered and prospectively designed comparative effectiveness study.

RNA 12, 73 significantly reduce the risk of COVID-19 infection and hospitalization compared to <unk>.

These data are reassuring and continue to underpin the strong global confidence governments health care systems and individuals hub in mrna COVID-19 vaccines and <unk>.

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Indeed, an example of that is the very recent announcement by the <unk>.

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For the preferential use at the Moderna vaccine and anyone over 12 years of age living with immuno compromise.

A similar pattern of results as seen from real World effectiveness studies in the United Kingdom.

The growth so I'm going to show you here come from the United Kingdom Health Security Agency looking at the effect of the <unk> buy in Tech our Mcdonough vaccines.

Paul Burton: The graphs I'm going to show you here come from the United Kingdom Health Security Agency looking at the effect of either the Pfizer-BioNTech or Moderna vaccine, and their vaccine effectiveness against hospitalization. First, let me show you the results in people who for their primary vaccination received the Pfizer-BioNTech vaccine, and were then boosted with either the Pfizer-BioNTech vaccine or the Moderna vaccine. We see retained protection against the Delta variant of concern in the field square.

Paul Burton: But we see waning of effect, in the field circles against Omicron. The same is true, though more pronounced, on the next part of this graph. And here you see individuals who received as their primary vaccine the AstraZeneca vaccine. Again, in this very large real world assessment. We can see that mRNA-1273 provides protection, against hospitalization, due to both Delta but to a lesser extent Omicron infection. Of note, we do see waning of protection over time against hospitalisation due to Omicron infection.

Yeah.

And that vaccine effectiveness against hospitalization.

First let me show you the results and people who for the primary vaccination received the funds up by in Tech vaccine and within this stayed with either the size or by intend vaccine or the <unk> vaccine.

We see retained protection against the Delta variant is concern in the field squares.

We see waning of effect.

In the field cycles against Omicron.

The same is true the more pronounced on the next part of this graph.

And here you see individuals who received as the primary vaccine the astrazeneca vaccine.

Again in this very large real world assessment, we can see that mrna 12 73, Chris provides protection.

Hospitalization.

Hey, Bert its delta, but to a lesser extent omicron infection.

Of note, we do see waning of protection over time against hospitalization due to AUM mix on infection.

Paul Burton: And this fits with the profound immunivasion we know to be the case with Omicron. But it is also a driver of our belief that not only will a boost of vaccination be required later in 2022, but also a booster will be required that protects against both the Delta and Omicron variants of concern, as Stephane announced earlier. This is because Delta, as we know, is associated with strong pathogenicity, and Omicron, as we have seen, due to its transmissibility and infectivity, is also associated with substantial morbidity and strain on healthcare systems through sheer bulk of cases.

And this fits with the profound immune evasion, we know to be the case with overcome.

It is also a driver availability.

Not only with a boost of explanation be required later in 2022.

Also boost will be required that protects against both the delta and omnicom variance is concern.

As Stefan and outstanding.

This is because the delta as we know is associated with strong pathogenicity and omicron as we have seen due to its transmissibility and infectivity is also associated with substantial morbidity and strain on health care systems through sheer bulk of cases.

Paul Burton: Hence, protection against both Delta and Omicron may well be necessary in the next boost to vaccination. On slide 10, we see data directly explaining the clinical phenomenon I just showed you. These data come from one of our previously conducted clinical studies. Sera from individuals immunized and boosted with mRNA-1273 is able to substantially neutralize the ancestral SARS-CoV-2 virus, D614G, shown here in black.

Hence protection against both Delta and <unk> may well be necessary in the next booster vaccination.

On slide 10, we see data directly explaining the clinical phenomenon I just showed you.

These data come from one of our previously conducted clinical studies.

Sarah from individuals immunized and boosted with mrna $12 73 is able to substantially neutralize the ancestral solace koby to virus D. Six one <unk> shown here in black.

Paul Burton: But to a lesser extent, Omicron, shown in red, and this is particularly true by six months following booster administration. Again, it is these data coupled with the real-world effectiveness data that I just showed you that leads us to believe an additional booster that will be needed later in 2022. Providing protection against both Delta and Omicron variants of concern. You can see this point made clearly again in slide 11, where we estimate the duration of protection against either the ancestral D614G strain or against omicron. With lower starting titers, protection against Omicron wanes and forwards to levels that would begin to allow breakthrough infection to occur due to Omicron and around nine months after boosting.

But to a lesser extent omicron, Sharon in Red and <unk>.

This is particularly true by six months following boosted administration.

Again it is these data coupled with the real world effectiveness data that I. Just showed you that leads us to believe an additional boost index will be needed later in 2022.

Providing protection against both Delta and omicron areas of concern.

You can see this point made clearly again in slide 11, where we estimate the duration of protection against either at the <unk> and.

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Against Homochrome.

With the lowest starting Titus protection against a macro wanes and forwards to levels that would begin to allow breakthrough infection to occur due to omicron.

Around nine months after boosting.

As leaders in mrna vaccines and COVID-19 disease, we will continue to monitor this carefully along with other emerging variants and continue to do whatever we can to provide people with a safe and highly effective vaccine booster for 2022 and years to come.

Paul Burton: As leaders in mRNA vaccines and COVID-19 disease, we will continue to monitor this carefully, along with other emerging variants, and continue to do whatever we can to provide people with a safe and highly effective vaccine booster for 2022 and years to come. We announced in January that we were able to go from identification of Omicron to testing of a new vaccine in humans in just two months. That is a remarkable testament to the Moderna mRNA platform and its utility.

We announced in January that we were able to go from identification of omicron to testing of a new vaccine in humans in just two months that is a remarkable testament to the Mcdonough mrna platform and its utility.

Slide 12 will be familiar to many of you as we first presented this slide at our vaccines day in April 2021.

Paul Burton: Slide 12 will be familiar to many of you as we first presented this slide at our Vaccines Day in April 2021. The graph is an illustration of the different phases of a pandemic to endemic continuum and its effect as measured by morbidity or disease burden over time. The shape of the graph was adopted from what we knew about previous pandemics at the time and what we expected from the current pandemic. Taking into consideration the increased levels of immunity, their immune systems collectively became familiarised, with the SARS-CoV-2 virus. These are through infection or vaccination.

The graph is an illustration of the different phases of the pandemic to endemic continue.

Its effect as measured by morbidity or disease burden over time.

The shape of the growth was adopted from what we knew about previous pandemics at the time.

We expected from the current pandemic taking into consideration the increased levels of immunity is that immune systems collectively became familiarized with the Sars cov two virus deepa.

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Paul Burton: As the graph shows, and with hindsight, it is easy to recognise that the very first wave of the pandemic, when all of the world's population was naive to this virus, caused the highest levels of morbidity and mortality. With each subsequent wave in mid 2021 with Delta, and in late 2021 and early 2022 with Omicron, the morbidity observed from these waves tended to be less severe, certainly relative to the first wave, as our immune systems became more experienced. Fighting, the SARS-CoV-2 virus. Beyond 2022 there still remains uncertainty.

As the graph shows and with hindsight. It is easy to recognize the very first wave of the pandemic when all of the world's population with naive to this virus caused the highest levels of morbidity and mortality.

With each subsequent wave in mid 2021 with Delta and in late 2021 early 2022 with Omicron morbidity observed from these waves tended to be less severe certainly relative to the first wave is that would mean systems became more experienced at fighting.

Lasalle is kobe to virus.

Beyond 2022, there still remains uncertainty however, given what we know now of other pandemics like the 1918 influenza pandemic and more importantly, what we have observed with the Sars Cov two pandemic. We do believe that we are transitioning into and then demick phase marked by period.

Paul Burton: However, given what we know now, other pandemics like the 1918 influenza pandemic, and more importantly, what we have observed with the SARS-CoV-2 pandemic, we do believe that we are transitioning into an endemic phase marked by a period of stability in case counts, hospitalizations, and deaths, at least in the Northern Hemisphere. We will continue to carefully monitor the situation in the Southern Hemisphere and winter approaches.

Stability in case counts.

Specializations in depth at least in the northern hemisphere.

We will continue to carefully monitor the situation in the southern hemisphere as winter approaches there.

Paul Burton: Thank you, on a background of continuing Delta and Omicron infection pressure. And we will work as quickly as possible to generate new specific boost of vaccine data. In the endemic phase, the virus will continue to circulate, but at rates that are static and more predictable. We continue to expect morbidity from the virus when it is endemic, and we believe like other respiratory virus. We will see a seasonal pattern of diseased birds emerge.

The background of continuing Delta and omicron infection pressure.

And we will work as quickly as possible to generate new specific booster vaccine data.

And the endemic phase the bias will continue to circulate rates the tough static a more predictable we continue to expect morbidity from the virus. When it is endemic and we believe like other respiratory viruses, we will see a seasonal pattern of disease, but emerge.

Paul Burton: But the good news is, because our immune system is now much more familiar with the virus, either through vaccination, infection or both. We do not expect that the majority of the population will be as susceptible to severe disease in the endemic phase as they were in the pandemic. Inset, as with other respiratory viruses, we believe protection from SARS-CoV-2 will be critical for populations that are likely to be most susceptible to severe disease and high bird.

The good news is because our immune system is now much more familiar with the virus either through vaccination infection or both we do not expect that the majority of the population will be as susceptible anticipated disease in the endemic phase, let's say, we're in the pandemic phase.

Instead as with other respiratory viruses, we believe protection from salons Covey too will be critical for populations that are likely to be most susceptible to severe disease and high bad disease.

Paul Burton: Providing the broadest protection possible will be a focus for us in the endemic phase. And we believe that Stphane mentioned multivalent facts, against SARS-CoV-2 and its variants will help achieve. As I alluded to earlier, respiratory viruses cause significant disease annually, and endemic coronaviruses are no exception to this. Slide 13 shows the incidence of community acquired infections leading to hospitalizations in New York City during the 2018-2019 season prior to the SARS-CoV-2 pandemic.

Providing the broadest protection possible will be a focus for us in the endemic phase and we believe as Stefan mentioned multivalent vaccines against Sars Covid, two and its variance will help achieve this.

As I alluded to earlier with spirit, two viruses caused significant disease annually.

And debit Corona viruses are no exception to this.

Slide 13 shows the incidence of community acquired infections, leading to hospitalizations in New York City.

During the 2018 to 2019 season.

To the Sars Cov two pandemic.

On the chart you can see that other endemic.

Paul Burton: On the chart, you can see that other endemic human coronavirus, in fact caused the highest level of hospitalizations in individuals between 65 and 79 years of age and those 80 years and above followed by RSV and influenza.

Corona viruses.

In fact cause the highest level of hospitalizations and individuals between 65, and 79 years of age and those 80 years and above followed by RSV in influenza.

Across OECD countries. The estimated impact from endemic human Corona viruses leads to over 1 million outpatient visits and 350000 hospitalizations and 20000 deaths in the over 65 year old population annually.

Paul Burton: Across OECD countries, the estimated impact from endemic human coronaviasis leads to over 1 million outpatient visits, 350,000 hospitalizations, and 20,000 deaths in the over 65 year of population annually. We believe SARS-CoV-2 will follow a similar pattern of seasonal disease as other respiratory viruses do and will impact vulnerable populations. Protecting populations against SARS-CoV-2 will be critical in the months and years to come. Protecting against combinations of respiratory viruses such as SARS-CoV-2, flu and RSV with a single yearly shot will be central to our strategy.

We believe <unk> will follow a similar pattern of seasonal disease as other respiratory viruses do and will impact vulnerable populations.

Protecting populations against <unk> will be critical in the months and needs to come.

Protecting against combinations of respiratory viruses, such as Sars Covid, two flu and RSV with a single geely shops will be central to our strategy.

Paul Burton: Stephen Hoge will shortly provide an update on our robust, ongoing strategy to achieve, So, in summary, the available real-world data continue to show the remarkable effectiveness of mRNA-1273. Real-world data shows that a 50-microgram boosted dose of mRNA-1273 provides protection against hospitalization caused by Omicron, but we note waning of antibody titers by six months post-boost.

Stephen Hoag will shortly provide an update on our robust ongoing strategy to achieve that.

So in summary, the available real World data continue to show the remarkable effectiveness of mrna $12 73.

Real World data shows that a 50 microgram booster dose of mrna 12, 73 provides protection against hospitalization caused by overcome but we note waning of antibody titers by six months post boosting.

We believe that our full 2022 booster will be needed globally and this lead is an mrna vaccines. We believe it is important to develop booster vaccines that will give us an opportunity to protect against omicron and future variance as we continue our fight to help in this pandemic.

Paul Burton: We believe that a full 2022 booster will be needed globally. And as leaders in mRNA vaccines, we believe it is important to develop booster vaccines that will give us an opportunity to protect against Omicron and future variants as we continue our fight to help end this pandemic. I will now hand over to Dr. Stephen Hoge to provide further updates on this topic and the Moderna pipeline. Thank you, Paul.

I will now hand over to Dr. Stephen Hope.

To provide further updates on this topic and the <unk> pipeline Steven.

Thank you Paul good morning, and good afternoon, everyone.

Stephen Hoge: Good morning and good afternoon, everyone. On slide 16, I'd like to briefly summarize our COVID-19 booster development strategy for the endemic, As Paul covered, the strategic rationale for a seasonal booster has three parts. First, we think neutralizing titers will wane, similar to the endemic human coronaviruses as Paul just described, that decline in neutralizing titers will increase the risk of breakthrough hospitalization in those at higher risk, specifically including older adults in the immune compromised.

On slide 16, I'd like to briefly summarize our COVID-19 boost your development strategy for the endemic phase So as Paul covered the strategic rationale for seasonal booster has three parts first we think neutralizing titers will win similar to the endemic human Coronavirus is as Paul just described.

That decline in neutralizing titers will increase the risk of breakthrough hospitalization in those at higher risk specifically, including older adults immune compromised.

We think the emergence of new variance of concern will also have the risk of accelerating waning and broadening the risk of breakthroughs to other populations.

Stephen Hoge: We think the emergence of new variants of concern will also have the risk of accelerating waning and broadening the risk of breakthroughs to other populations. So the desired features for our Northern Hemisphere Fall and Winter 2022 Booster are described here.

So the desired features for our northern Hemisphere fall and winter 2022 booster are described here.

Stephen Hoge: First, we'd like to improve the durability of protection for neutralizing antibodies against Omicron and Omicron mutations to at least six months. That will provide full protection through the Northern Hemisphere fall-winter infection season. We'd like to retain the high and durable protection we've been seeing with a prototype vaccine against Delta and the ancestral. And third, we'd like to broaden cross-protective immunity to the extent possible to increase the potential for protection against a new emergent variant of concern, which could emerge perhaps from the Southern Hemisphere this mid-year.

First we'd like to improve the durability of protection for neutralizing antibodies against Omicron and omicron mutations to at least six months that will provide full protection through the northern hemisphere fall winter infection season.

We'd like to retain the high and durable protection, we've been seeing with the prototype vaccine against Delta and the in central streams.

And third we'd like to broaden cross protective immunity to the extent possible to increase the potential for protection against the new emerging varian of concern, which could emerge perhaps from the southern hemisphere. This mid year.

So on slide 17, I'll quickly summarize our strategy for developing an updated booster for fall 2022.

Stephen Hoge: So on slide 17, I'll quickly summarize our strategy for developing an updated booster for fall 2022. We are currently evaluating three different booster strategies in adults age 18 plus. The first, as both Paul and Stphane have mentioned, is a bivalent booster vaccine made up of the prototype mRNA-1273 and an Omicron specific mRNA-1273-529. This bivalent has been called 214.

Stephen Hoge: We are also evaluating if we previously announced an OMACON specific blister at marnay1273.529. And of course, we will continue to evaluate our prototype booster, mRNA-1273, for which there is a large body of real-world evidence, as Paul mentioned. We're evaluating these three different approaches across two studies in the United States and the United Kingdom, a phase two study in the United States of approximately 750 participants, and a 3,000 participant study in the United Kingdom.

We are currently evaluating three different booster strategies in adults age 18, plus the first as both Paul and Stefan had mentioned is a buyback booster vaccine made up the prototype and $12 73 and in OMA cone specific 12 to 73, 5%.

Stephen Hoge: Both are looking at both bidalent and omicron specific boosters, and both will be looking at both third and fourth dose of those boosters. In the UK study, we'll also be looking at heterologous boosting, including on the background of other mRNA vaccines and non-mRNA. Now, I'd like to take a moment on slide 18 to provide some scientific insight into why we believe the bivalent vaccine booster for the fall of 2022 offers a potential advance, Slide 18 includes data on some of our prior by valent booths.

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We are also evaluating as we previously announced and Omar Khan specific booster. Good morning, 12, $73 five to nine.

And of course, we will continue to evaluate our prototype booster. Good morning, $12 73 for which there is a large body of real world evidence as Paul just described.

We are evaluating these three different approaches across two studies in the United States and United Kingdom Phase III study in United States of approximately 750 participants and.

<unk> 3000 participants study in the United Kingdom, both are looking at both <unk> and Micron specific boosters and both will be looking at both third and fourth dose of those boosters.

In the UK study, we will also be looking at heterologous boosting including on the background of other mrna vaccines and non mrna vaccines.

Now I'd like to take a moment on slide 18 to provide some scientific insight into why we believe the bivalent vaccine booster for the fall 2022 offers a potential advantage.

Slide 18 includes data on some of our prior bivalent boosters and this data is emerging data suggests to us that there may be an opportunity to improve durability against variance of concern while preserving activity against <unk>.

Stephen Hoge: And this data, this emerging data, suggests to us that there may be an opportunity to improve durability against variants of concern while preserving activity against the ancestral, This data is based on one of our prior bivalents, mRNA-1273.211, or 2-11 for short.

This data is based on one of our prior by Valens in more than a $12 73 to one one or 211 for sure.

Stephen Hoge: And 2-11, as you may recall, was based on the 1273 vaccine and the beta variant of concern, which emerged approximately a year ago. When we compare over time how the two different booster strategies, our prototype booster on the left-hand column here and our bivalent booster on the right-hand column, Due against the two different virus variants that were in the vaccine, you see an emergence of potential improvement in durability. So first, to orient you to the slide, mRNA-1273 was given at 50 micrograms as a booster to those who had previously received two doses of the mRNA-1273 vaccine.

211, as you May recall was based on the $12 73 vaccine and the beta version of concern, which emerged approximately a year ago.

When we compare over time, how the two different booster strategies, our prototype booster on the left hand column here and are by their with booster on the right hand column here.

Do against the two different.

Virus variants that were in the vaccine you see an emergence of potential improvement in durability. So first Orient you to the slides.

Stephen Hoge: And on the top left panel, you'll see how the neutralizing titers or pseudovirus neutralizing titers against the ancestral strain of the virus, the D614G virus in our validated. Underneath there, you'll see how the pseudovirus neutralization titers against the beta variant of concern in blue. And in the middle column, you'll contrast that with a bivalent 2-1-1 booster, which in this case included the beta variant of concern, again, at the same dose level, 50 micrograms. Top right panel is the Ancestral Virus, D614G, and lower right is the beta variant of concern or the B.1.351.

And more than a 12 73 was given the 50 microgram does a booster did those who had previously received two doses of mrna 12 73 vaccine.

And on the top left panel, you'll see how the neutralizing titers are pseudo virus neutralizing titers against the ancestral strains of the virus the <unk> virus in our validated clinical assays.

Underneath there youll see how those.

<unk> suite of virus neutralization titers against the beta version of concern in Blue.

And in the Middle column, you contrast that with the Bivalent 211 booster, which in this case included the beta version of concern again at the same dose level 50 micrograms top right panel as Dan Cesspool variant of concern.

Virus <unk>.

And lower right is the beta version of concern or the B, one dot 351.

Stephen Hoge: Now, as you'll note, comparing the performance against the ancestral D614G virus. Both mRNA-1273 and the bivalent beta-containing booster do a good job boosting neutralizing titers by day 29 after the booster. So one month post-booster, neutralizing titers are approximately 1800 for 1273 and 2200 for the bivalent. And importantly, as we test the serum six months after booster, noted as day 181 here, you'll see that neutralizing titers remain high, approximately 1,000 in both booths.

Now as Youll note comparing.

The performance against the ancestral <unk>, both in the morning, <unk> 73, and the bivalent beta containing booster.

Do a good job boosting neutralizing titers by day 29 after the district. So one month post booster neutralizing titers are approximately 1800 for $12 73, and 'twenty 200 for the bivalent.

And importantly, as we test the serum six months. After booster noted is day 181 here.

Youll see that neutralizing titers remained high at approximately 1000 in both boosters.

Stephen Hoge: The situation against the variant of concern, in this case beta, is slightly different. Again, both boosters increased neutralizing titers by day 29, one month after booster, to quite reasonable levels, approximately 1,000 in both cases. However, when you follow up six months, there is a difference in the neutralizing titers that emerge.

So the situation against the Varian of concern in this case beta just slightly different.

Again, both boosters increased neutralizing titers by day 29, one month after booster to quite reasonable levels approximately a thousand in both cases.

However, when you follow out six months there is a difference in the neutralizing titers that emerges.

Stephen Hoge: And not surprisingly, the bivalent booster, which includes the beta variant of concern, starts to see more durable neutralizing titers, 402 as noted here, as opposed to 154 for mRNA-1273. So, in summary, six months after a 2-1-1 bivalent booster, the neutralizing titers against the beta variant of concern appear to be more durable than with just the prototype booster, and the durability or the rate of decline for the beta-neutralizing titers more closely matches that seen for the ancestral virus following the bivalent 2-in-1 boost.

And not surprisingly the bivalent booster, which includes the beta version of concern starts to see more durable neutralizing titers 402 as noted here as opposed to a 154 for $12 73.

So in summary, six months after a 211 bivalent booster the neutralizing titers against the beta version of concern appear to be more durable than with just a prototype booster.

And the durability or the rate of decline for the beta neutralizing titers more closely matches that seen for the ancestral virus. Following the bivalent 211 booster, including the beta version of concern therefore appears to be improving the durability of neutralizing titers against that bearing a concern.

Stephen Hoge: And including the beta variant of concern, therefore appears to be improving the durability of neutralizing titers against that variant of, Now on the next slide, slide 19, we have that same data, but now plotted as a function of time to help you visualize a little more clear. On the left-hand side, we're contrasting the mRNA-1273 booster as a black, against the five-valent beta-containing booster in the red line. [inaudible] On the left-hand side, you're again looking at the Ancestral D614G neutralizing titers.

On the next slide Slide 19, we had that same data, but now plotted as a function of time to help you visualize a little more clearly.

On the left hand side.

We're contrasting the mrna 12 73 booster as a black line.

Against the bivalent beta containing booster and the Red line.

On the left hand side, you again looking at the ancestral DCM 14, G neutralizing titers and as you can see following a booster of approximately six months after post dose two neutralizing titers for both of the boosters, the bivalent and the prototype vaccine increased significantly.

Stephen Hoge: And as you can see, following a booster approximately six months after Bostos 2, neutralizing titers for both of the boosters, both bivalent and the prototype. Increased Significant, and the data we have out to six months. If you project that forward as we do with the dotted lines, it suggests that we will maintain quite high neutralizing titers, perhaps as long as one year. Now the situation on the right hand side highlights we think the potential for improving durability with a bivalent vaccine. Again, here, the black line is mRNA-1273, and the red line is a bivalent beta-containing booster. The same goes...

And the data we have up to six months.

You project that forward as we do with the dotted lines suggests that we will maintain quite high neutralizing titers, perhaps as long as one year.

Now the situation on the right hand side highlights, we think the potential for improving durability with the bivalent vaccine.

Again here the Black line is more than $12 73, and the Red line is the bivalent beta containing booster the same dose level.

Stephen Hoge: While both boosters increase neutralizing titers to approximately 1,000 within one month of boosting. What starts to emerge six months later is a different degree of durability in those neutralizing titers, with the bivalent vaccine containing the beta antigen doing slightly better, as you can see with the red line. If you project that forward, it suggests that the bivalent vaccine neutralizing titers against the beta variant of concern will remain quite high, perhaps as long as a year, whereas with a prototype vaccine, those neutralizing titers appear to be decaying more quickly, back towards baseline levels or pre-booster levels by approximately eight to nine months. On slide 20.

While both boosters increased neutralizing titers to approximately 1000 within one month of boosting.

What starts to emerge six months later as a different degree of durability in those neutralizing titers with the bivalent vaccine containing the beta antigen doing slightly better as you can see with the Red line.

And if you project that forward it suggests that the bivalent vaccine.

Neutralizing titers against a beta version of concern will remain quite high perhaps as long as a year.

With a prototype vaccine those neutralizing titers appear to be the key more quickly.

Back towards baseline levels are pre booster levels by approximately eight to nine months.

On slide 20, just to quickly summarize therefore, where we are in COVID-19 booster development for fall 2022.

Stephen Hoge: Quickly summarize, therefore, where we are in COVID-19 booster development for fall 2022. We believe that a seasonal booster will be necessary to prevent breakthrough diseases, including hospitalization in vulnerable populations, and we believe that the continued evolution of the virus is going to continue to put pressure on pre-existing immunity, whether that's naturally derived or vaccine-provided. We think the fall 2022 booster should reflect the diversity of circulating mutations that are out there in order and seek to achieve greater than six months of neutralizing titer durability to increase the potential for protection throughout the entire fall season.

We believe that our seasonal booster will be necessary to prevent breakthrough diseases, including hospitalization and vulnerable populations.

We believe that the continued evolution of the virus is going to continue to put pressure on preexisting immunity, whether that's naturally derived or vaccine provided.

We think the fall 2022 booster should reflect the diversity of circulating mutations that are out there.

And seek to achieve greater than six months of neutralizing titer durability increase the potential for protection throughout the entire fall season. In this case, we think September through February .

Stephen Hoge: In this case, we think September through February. So Moderna is developing an Omicron-containing bivalent booster based on data that we have from prior bivalent candidates that suggests that incorporating the variant of concern or those mutations from that variant of concern has the potential to improve the durability against such a mutation. Now, moving to slide 21.

So <unk> is developing an omicron containing bivalent booster based on data that we have from prior bivalent candidates that suggests that incorporating the varian of concern of those mutations from that during concern has the potential to improve the durability against such great concern.

Moving to slide 21.

Stephen Hoge: Just quickly catching up on other developments in our COVID-19 vaccine. We have made progress in primary series and booster in adolescent and pediatric population. So in adolescence first, we've received regulatory approvals for spike facts in Europe, United Kingdom, Australia, Canada and many other countries.

Just quickly catching up on other developments in our COVID-19 vaccine.

We have made progress in primary series and booster in adolescent and pediatric populations.

So in adolescence first we have received regulatory approvals for <unk> in Europe , United Kingdom, Australia, and Canada and many other countries.

Stephen Hoge: In the U.S., we plan to submit an EUA for 100 micrograms of MRA-1273 in adolescents that are immune compromised or at elevated risk of severe outcomes, and we're also evaluating the potential of a lower dose, 50 micrograms as a primary series. And lastly, as has been noted previously. We're preparing to submit data for 50 micrograms as a booster dose in adolescents and 50 micrograms as the booster dose in adults as well. And that will include data on heterology.

In U S. We plan to submit an EUA for 100 micrograms of more than 12 months 73, and net of lessons that are immune compromised or an elevated risk of severe outcomes and we're also evaluating the potential of a lower dose 50 micrograms as a primary series.

And lastly, as has been noted previously.

We are preparing to submit data for 50 micrograms as a booster dose in adolescence, and 50 micrograms as the booster dose in adults as well and that will include data on heterologous boosting.

In pediatrics or the six to 11 year old we received provisional approval for <unk> in Australia and submitted to multiple other international regulatory agencies and expect authorization shortly.

Stephen Hoge: In Pediatrics for the 6 to 11 year old, we've received provisional approval for spike vacs in Australia and submitted to multiple other international regulatory agencies and expect authorization shortly. The U.S. Submission is pending alignment with the United States FDA on Adolescent Applications. And we will also continue to evaluate lower doses, including a 25-micron primary series. Finally, in the youngest, 6-month to 5-year-old pediatric population.

The U S submission is pending alignment with the United States FDA on Adam on the Atlassian application and we will also continue to evaluate lower doses, including a 25 microgram primary series dose.

Finally in the youngest six months to five years old pediatric population, we expect data on our 25 microgram two dose primary series in the first quarter and depending that data, we will plan to submit to regulators.

Stephen Hoge: We expect data on our 25-microgram, two-dose primary series in the first quarter, and depending that data, we'll plan to submit to regulators. We're also continuing to evaluate lower doses and the potential of a third dose in that. Pivoting to the broader respiratory vaccine portfolio on slide 2022, beyond COVID-19, we continue to make progress across all of our respiratory, Fonmentioned, our flu vaccine is fully enrolled with Phase 2, and pending that data, we will prepare to move forward, which we still anticipate doing in 2022, into a Phase 3 study.

We're also continuing to evaluate lower doses and the potential of a third dose in that population.

Pivoting to the broader respiratory vaccine portfolio on slide 2022 beyond COVID-19, we continue to make progress across all of our respiratory vaccines as Stefan mentioned, our flu vaccine is fully enrolled with phase II and pending that data, we will prepare to move forward, which we still anticipate doing in 2000.

22 into a phase III study.

Stephen Hoge: We're also preparing to start a combination flu and COVID vaccine, which is currently in preclinical. But we expect to start the phase one study this year. Our older adult RSV program has started its phase three study portion, and that pivotal study is ongoing. We have a pediatric RSV study, which we will move forward and finish. We have also two different respiratory combination vaccines.

We're also preparing to start a combination flu and Covid vaccine, which is currently in preclinical, but we expect to start the phase one study this year.

Our older Adult RSV program has started its phase III study portion.

And that pivotal study is ongoing.

We have a pediatric RSV study, which we will move forward in phase one.

We have also two different respiratory combination vaccines first the human Metapneumovirus apparent blurring the virus three vaccine, which is in phase one b and is now fully enrolled and.

Stephen Hoge: First, the human melanoma virus and parenteral virus three vaccine, which is in phase one B and now fully enrolled, and an RSV plus HMPV vaccine, which remains in preclinical development and we hope. Moving now to latent and public health vaccines on slide 23. As discussed, CMV continues to enroll in the phase three CM victory study. We have also moved forward to new latent virus vaccines into clinical testing. Our EBV vaccine to prevent infectious mononucleosis is in phase one.

And in RSV, plus <unk>, PV vaccines, which remains in preclinical development and we hope to start shortly.

Moving now to Leighton and public health vaccines on slide 23 as discussed CMV continues to enroll in the phase III and victory study.

We have also moved forward to new latent virus vaccines into clinical testing, our EBV vaccine to prevent infectious mononucleosis is in phase one and our HIV. Our first HIV vaccine <unk> 16, 44 is also in phase one.

Stephen Hoge: And our HIV, our first HIV vaccine, mRNA 1644, is also in phase one. We announced two new development candidates, which I'll cover briefly in the next couple of slides, against HSV and VZV. And our public health vaccines against Zika and Nipah continue to. Briefly on slide 24, I'd like to introduce the first of our two new development candidates in this, and Moderna 1608 is our vaccine against herpes simplex virus 2. HSV-2 primarily infects the genitals and establishes lifelong latent infections within the sensory neurons.

We announced two new development candidates, which I'll cover briefly in the next couple of slides against HSV, <unk> and our public health vaccine against Zika and NEPA continued to progress.

Briefly on slide 24, I'd like to introduce the first of our two new development candidates in this space.

Im wondering <unk> eight is our vaccine against herpes simplex virus two.

HSV, two primarily infection, the genitals and establishes lifelong latent infections within the sensory neurons theres a significant burden of disease in developed markets, including approximately 18 million people, who reaches HSV positive HSV, two positive and the United States globally that represents about five.

Stephen Hoge: There is a significant burden of disease in developed markets, including approximately 18 million people who are HSV positive and HSV2 positive in the United States. Globally, that represents about 5% of the population. The Primary Burden of Disease is a reduction in quality of life recurrently. Our mRNA-1608 vaccine encodes antigens on the surface of the HSV virus and has been able to induce very strong immune responses, as illustrated in the figure to the right. Neutralizing Titers in Mice Following an HSV-2 Vaccine with mRNA 1608, are significantly above the levels seen in human sera from those who are seropositive.

5% of the population.

<unk> burden of disease is a reduction in quality of life.

Current lesions.

Our <unk> 16 of weight vaccine encodes antigens on the surface of the HSV Pirates and has been able to induce very strong immune responses as illustrated in the figure to the right.

Neutralize the titers in mice following an HSV two vaccine with <unk> 16 of late.

Are significantly above the levels seen in human serum from those who are seropositive.

Stephen Hoge: This gives us reason to believe that we will be able to provide a significant benefit with this vaccine in this population. The second development candidate is on the following slide, slide 25. This is our mRNA 1468 program against herpes zoster or shingles. Herpes Zoster is caused by the reactivation of latent varicella zoster virus or BCV for short.

This gives us reason to believe that we will be able to provide a significant benefit with this vaccine in this population.

The second development candidate is on the following slide slide 25.

This is our <unk> 14, 68 program against Herpes zoster shingles.

Herpes zoster is caused by the reactivation of latent varicella zoster virus or BCB for Schwartz.

Stephen Hoge: It's principally a disease that's seen as a result of declining immunity in older adults where protection against VZV declined, leading to reactivation of the virus and painful and very itchy leashes. Herpes zester occurs in about one out of three adults in their lifetime, and the instance is increasing as as populations age and particularly increases over the, On the right-hand side is previously published data in the Journal of Vaccine on our VZV.

Simply a disease that is seen as a result of declining annuity in older adults where protection against <unk> declined leading to reactivation of the virus and painful and very itchy lesions.

Herpes zoster occurs in about one out of three adults in their lifetime and the incidence is increasing as is.

As populations age and particularly increases over the age of system.

On the right hand side as previously published data in the journal of vaccine on our <unk>.

Stephen Hoge: Vaccine. In this case, mRNA 1468. The R vaccine in non-human primates was compared against the protein and protein plus adjuvant as a stand-in, a proxy for the Shingrix vaccine, which is already approved for this indication. As you note on the right, in non-human primates.

Vaccine in this case.

Hey morning, $40 68.

Our vaccine in nonhuman primates was compared against.

Right.

The protein and protein plus adjuvant as a stand in a proxy for the shingles vaccine for which is already approved for this indication as you noted the right <unk>.

Human primates.

Stephen Hoge: The mRNA vaccine against GE resulted in significant and elevated neutralizing titers after two doses, and we believe will provide the basis for a strong potential clinical benefit with mRNA-14, Moving now to our Therapeutic Pipeline. We continue to make progress across a range of different programs. On Slide 26, I'll note a few very quickly.

The mrna vaccine against GE resulted in significant and elevated neutralizing titers. After two doses and we believe will provide the basis for a strong potential clinical benefit.

They're more in a <unk> 68.

Moving now to our therapeutic pipeline.

We continue to make progress across a range of different programs on slide 26, I'll note a few very quickly.

Stephen Hoge: First, our PCV program in Phase 1 is ongoing and Phase 2 is fully enrolled. We expect data in the fourth quarter of 2022. We're also going to provide a bit of an update on the checkpoint vaccine, a newly announced development in Canada in just a minute, highlighting its other therapeutic areas. Our VegF program continues to move forward in phase two with AstraZeneca.

First our PCV program in Phase one is ongoing in the phase two is fully enrolled we expect data in the fourth quarter of 2022.

We were also going to provide a bit of an update on the checkpoint vaccine our newly announced development candidate in just a minute.

Highlighting in other therapeutic areas. Our VEGF program continues to move forward in phase two with Astrazeneca.

Stephen Hoge: And in rare diseases, our PA and MMA programs continue to enroll in their phase one with the phase one first dose level cohort fully enrolled in PA and continued enrolling of additional cohorts. We also continue to make progress across all of our other preclinical programs in rare diseases, including GSD1A, PKU, CN1, and the Cystic Fibrosis Program with BERT. On slide 27, I'd like to briefly cover our latest development candidate, a checkpoint vaccine to promote anti-checkpoint T cell responses in cancer.

And in rare diseases or <unk> in MMA programs continue to enroll in their phase one.

With the phase one cohort dose level cohort fully enrolled in Ta.

Continued enrolling additional cohorts.

We also continue to make progress across all of our other preclinical programs in rare diseases, including GST, Renee PKU, San Juan and the cystic fibrosis program.

Vertex.

On slide 27, I'd like to briefly cover our.

Latest development candidates checkpoint vaccine to promote anti checkpoint T cell responses.

In cancer.

Stephen Hoge: Otherwise known as mRNA, 40359. [inaudible] So briefly, the objective of this program is to stimulate effector T cells that target and kill suppressive immune and cancer cells that express high levels of target checkpoint antibodies. It's been previously identified that there are pre-existing IDO and PDO 1 specific T cells that have been identified in cancer patients and tumors.

Otherwise known as <unk> more than $843 59.

So briefly the objective of this program is to stimulate effector T cells that target and kill suppressive immune in cancer cells that express high levels of target checkpoint antigen.

We previously identified that there are pre existing <unk> and PDL one specific T cells that have been identified in cancer patients in tumors.

Stephen Hoge: Ido and PDO 1 specific T cells can kill and remove the immunosuppressive regulatory immune cells and cancer cells that over express these answers, is an important counterbalance that helps liberate the immune response against the tumor. Our vaccine can expand IDO and PD-L1 specific T-cells in preclinical models. The vaccine-induced direct tumor cell killing can facilitate recognition of tumor-associated antigens by other cytotoxic T cells, leading to more broad tumor killings, systemic blockade with PD-1 or PD-L1 antibodies may further amplify this effect.

<unk> and PDL, one specific T cells can kill and remove the immunosuppressive regulatory immune cells and cancer cells that over express these antigens.

An important counterbalance that helps liberate the immune response against the tumor.

Our vaccine can expand Idaho, and PD lone specific T cells in preclinical models.

And the vaccine induced direct tumor cell, killing Ken facilitate recognition of tumor associated antigens by other studies toxic T cells, leading to more broad tumor killing.

Systemic blockade with PD, one or PD lone antibodies may further amplify this effect we.

Stephen Hoge: We will initially be developing mRNA 4359 against indications including first line cutaneous melanoma stage 3b and first line non-small cell fungal. With that, I'd like to turn it over to David to walk you through the process. Okay, thank you, Stephen. We're providing today the analysis of actual 2021 fourth quarter and full year results, along with a view of key drivers of financial performance going forward. 2021 was a transformative year for the company as it marked a transition from an R&D focused entity to a commercial stage company. I'm very pleased with our performance and wanted to thank all of our employees at Moderna for their dedication and response to the many challenges during this unprecedented company scale up.

We will initially be developing mrna $43 59 against indications, including first line cutaneous melanoma stage III B and first line non small.

Non small cell lung cancer.

With that I'd like to turn it over to David did walk you through the financials.

Okay. Thank you Steven.

We're providing today the analysis so the actual 2021 fourth quarter and full year results along with a view of key drivers of financial performance going forward.

2021 was a transformative year for the company as it marks a transition from an R&D focused entity to a commercial stage company I am very pleased with our performance and wanted to thank all of our employees at <unk> for their dedication in response to the many challenges.

This unprecedented companies scale up.

David Muehne: Turning now to slide 29, starting with an overview of our sales performance. Total product sales in the fourth quarter of 2021 were $6.9 billion, representing 297 million doses delivered to our customers. This compares to sales of $4.8 billion for 208 million doses in Q3 and $199 million in Q2. We increased our dose supply in the fourth quarter by 43% compared to Q3 after a relatively stable picture in Q2 and Q3 as we successfully focused on removing bottlenecks in our supply chain network.

Turning now to slide 29, starting with an overview of our sales performance.

Total product sales in the fourth quarter of 2021 were $6 $9 billion, representing 297 million doses delivered to our customers.

This compares to sales of $4 8 billion for 208 million doses in Q3, and 199 million doses in Q2.

We increased our dose supply in the fourth quarter by 43% compared to Q3 after a relatively stable picture in Q2 and Q3 as we successfully focused on removing bottlenecks in our supply chain network.

David Muehne: Sales of our COVID vaccine have shifted in terms of geographic mix over the course of the year, in line with our expectations and the ramp up of our international manufacturing capabilities. Sales outside the U.S. to the rest of the world were $6.1 billion in the fourth quarter, reflecting 252 million doses. And sales to the U.S. government were $0.7 billion in the fourth quarter, reflecting 45 million doses sold.

Sales of our Covid vaccine have shifted in terms of geographic mix over the course of the year in line with our expectations and the ramp up over international manufacturing capabilities.

Sales outside the U S to the rest of the World were $6 1 billion in the fourth quarter, reflecting 252 million doses and the sales to the U S. Government were <unk> 7 billion in the fourth quarter, reflecting 45 million doses sold.

For the full year, we sold 807 million doses, resulting in product sales of $17 7 billion.

David Muehne: For the full year, we sold 807 million doses, resulting in product sales of $17.7 billion. We generated sales of $5.4 billion in the US and $12.3 billion with customers in the rest of the world. Approximately 25% of our delivered doses went to low and middle income countries, either through direct sales or facilitated by donations from other customers. Turning to slide 30 to go into more detail of our Q4 results. The transformation of Moderna from an R&D focused biotech company to a commercial stage business continues to be apparent when reviewing our financial results.

We generated sales of $5 4 billion in the U S and $12 3 billion with customers on the rest of the world.

Approximately 25% of our deliver doses went to low and middle income countries, either through direct sales or facilitated by no nations from other customers.

Turning to slide 30 to go into more detail of our Q4 results.

The transformation of <unk> from an R&D focused biotech company to a commercial stage business continues to be apparent when reviewing our financial results.

David Muehne: The comparison of the fourth quarter of 2021 to prior year is not very meaningful due to the significant growth, which is why I primarily focus on the quarter over quarter comparison relative to Q3 on this slide. Total revenue was $7.2 billion in the fourth quarter of 2021 compared to $5 billion in the third quarter and $0.6 billion in the prior year period.

The comparison of the fourth quarter of 2021 to prior year is not very meaningful due to the significant growth, which is why primarily focus on the quarter over quarter comparison relative to Q3 on the slide.

Total revenue was $7 2 billion in the fourth quarter of 2021 compared to 5 billion in the third quarter and <unk> 6 billion in the prior year period.

David Muehne: The increase of total revenue was driven by the sale of the company's COVID-19 vaccine. Product sales in Q4 2021 were $6.9 billion, compared to $4.8 billion in the third quarter, an increase of 44%. Cost of sales was $952 million or 14% of companies.

The increase of total revenue was driven by the sale of the company's COVID-19 vaccine product sales in Q4, 2021 for $6 9 billion compared to $4 8 billion in the third quarter, an increase of 44%.

Cost of sales was $952 million or 14% of companies.

David Muehne: Product Sales in the fourth quarter compared to 722 million, or 15% of product sales in the third quarter. The quarter over quarter percentage improvement was driven by favorable manufacturing costs, while the average selling price remained relatively stable.

Product sales in the fourth quarter compared to $722 million or 15% of product sales in the third quarter.

The quarter over quarter percentage improvement was driven by favorable manufacturing cost as the average selling price remained relatively stable.

David Muehne: Research and Development Expenses were $648 million in the fourth quarter compared to $520 million in the third quarter and $759 million in the same period in 2020. The higher spend versus prior quarter was primarily driven by increased clinical trial expenses from her expanding and maturing development portfolio. The decrease in spending compared to 2020 was mainly due to the fact that the prior year number includes approximately $200 million of pre-launch inventory costs.

Research and development expenses were $648 million in the fourth quarter compared to $521 million in the third quarter and $759 million in the same period in 2020.

The higher spend versus prior quarter was primarily driven by increased clinical trial expenses from our expanding and maturing development portfolio. The.

The decrease in spending compared to 2020 was mainly due to the fact that the prior year number includes approximately $200 million.

Pretty launch inventory costs.

Selling general and administrative expenses were $201 million for Q4 compared to $168 million in the prior quarter and $79 million for the same period in the prior year.

David Muehne: Selling general and administrative expenses were $201 million for Q4 compared to $168 million in the prior quarter and $79 million for the same period in the prior year. 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 buildup. Provision for income taxes was $542 million in the fourth quarter, following $219 million in the third quarter and an insignificant amount in the prior year. Her effective tax rate for the fourth quarter was 10%.

The growth in spending was driven by the commercialization of our COVID-19 teen vaccine globally with continued investments in personnel and outside services in support of the accelerated company buildup.

Provision for income taxes was $542 million in the fourth quarter following $219 million in the third quarter and an insignificant amount in the prior year.

Our effective tax rate for the fourth quarter was 10%.

David Muehne: The quarter over quarter increase was primarily driven by higher earnings. [inaudible] Let me remind you of the fact that we had a net operating loss carry forward of 2.3 billion at the end of 2020. In 2021, we released the valuation allowance against the related deferred tax assets, which resulted in a non-recurring full year benefit to our effective tax rate of about five percentage points. We recorded net income of $4.9 billion in Q4 compared to $3.3 billion in Q3, an increase of 46%. This compares to a loss of $0.3 billion in Q4 of last year. Diluted earnings per share for Q4 2021 were $11.29.

Quarter over quarter increase was primarily driven by higher earnings.

Let me remind you of the fact that we had a net operating loss carryforward of $2 3 billion at the end of 2020.

In 2021, we released the valuation allowance against the related deferred tax assets, which resulted in a nonrecurring full year benefit to our effective tax rate of about five percentage points.

We recorded net income of $4 9 billion in Q4 compared to $3 3 billion in Q3, an increase of 46%.

This compares to a loss of <unk> 3 billion in Q4 of last year.

Diluted earnings per share for Q4, 2021 were $11 29.

David Muehne: Turning now to full year financial results on slide 31. Total revenue was $18.5 billion for the full year 2021 compared to $0.8 billion in 2020. The significant growth was driven by the sales of 807 million doses of the company's COVID-19 vaccine, resulting in product sales of $17.7 billion. Cost of sales was $2.6 billion, or 15% of the company's product sales in 2021, including third-party royalties of $641 million. A portion of the inventory costs associated with this year's product sales was expensed as pre-launch inventory in 2020. If inventory sold for the full year was valued at cost, our cost of sales for the period would have been $2.8 billion or 16% of product sales.

Turning now to full year financial results on slide 31.

Total.

David Muehne: Research and development expenses were $2 billion in 2021 compared to $1.4 billion in 2020. The growth in spending in 2021 was driven by clinical trial expenses for expanding pipeline and the related organizational build out. Selling general and administrative expenses were $0.6 billion for the full year 2021 compared to $0.2 billion in 2020. The growth in spending in 2021 was mainly due to increases in consulting and outside services, personnel related costs, marketing expense and distributor fees, primarily attributable to the company's COVID-19 vaccine commercialization related activities and increased headcount. Provision for Income Taxes was 1.1 billion for the full year 2021, compared to an insignificant amount in 2020.

<unk> was $18 5 billion for the full year 2021, compared to <unk> 8 billion in 2020.

The significant growth was driven by the sales of 807 million doses of the company's COVID-19 vaccine, resulting in product sales of $17 7 billion.

Cost of sales was $2 6 billion or 15% of the company's products sales in 2021 <unk>.

Including third party royalties of $641 million.

A portion of the inventory costs associated with this year's product sales was expense does prelaunch inventory in 2020.

It's inventory sold for the full year was valued at cost our cost of sales for the period would have been $2 8 billion or 16% of product sales.

Research and development expenses were $2 billion in 2021 compared to $1 4 billion in 2020.

The growth in spending in 2021 was driven by clinical trial expenses for our expanding pipeline and the related organizational buildup.

Selling general and administrative expenses were <unk> 6 billion for the full year 2021, compared to <unk> 2 billion in 2020.

The growth in spending in 2021 was mainly due to the increase is it consulting and outside services personnel related costs marketing expenses and distributor fees, primarily attributable to the company's COVID-19 vaccine commercialization related activities and incur.

<unk> head count.

Provision for income taxes was $1 1 billion for the full year 2021, compared to an insignificant amount in 2020.

David Muehne: The effective tax rate in 2021 was eight percent. [inaudible] It was lower than the U.S. statutory rate, primarily due to a non-recurring benefit related to the release of the valuation allowance. The ongoing benefit of the foreign-derived intangible income deduction, as well as benefits related to stock-based compensation. Now, it didn't come with $12.2 billion for the full year 2021, compared to a net loss of 0.8 billion in 2020. Diluted earnings per share were $28.29 for the full year 2021.

The effective tax rate in 2021 was 8%.

Lower than the U S statutory rate, primarily due to a nonrecurring benefit.

Later to the release of the valuation allowance.

Ongoing benefit for the foreign derived intangible income deduction as well as benefits related to stock based compensation.

Net income was $12 $2 billion for the full year 2021, compared to a net loss of <unk> 8 billion in 2020.

Diluted earnings per share were $28 29 for the full year 2021.

Turning to cash and cash deposits on slide 32.

David Muehne: Turning to cash and cash deposits on slide 32. We ended 2021 with cash and investments of $17.6 billion compared to $15.3 billion at the end of Q3. The increase is driven by our commercial activity. The balance of cash deposits for future product supply was $6 billion at the end of the year compared to $6.7 billion at the end of Q3. The reduction quarter over quarter is driven by commercial deliveries against our commitment.

We ended 2021 with cash and investments of $17 6 billion compared to $15 3 billion at the end of Q3.

The increase was driven by our commercial activity.

The balance of cash deposits for future product supply was $6 billion at the end of the year compared to $6 7 billion at the end of Q3.

The reduction quarter over quarter is driven by commercial deliveries against our commitments.

David Muehne: Now turning to slide 33. Now turning to slide 33. Our capital allocation priorities remain unchanged.

Now turning to slide 33.

David Muehne: Our top investment priority has been and will continue to be reinvesting in the base business across multiple areas. For R&D, we have significantly increased our spending in 2021 to approximately $2 billion. And we expect to continue to further increase our spending in this area to advance and accelerate our pipeline, both for existing and new programs. We're also further increasing our investment into our global manufacturing network in digital automation and AI, as well as scaling up our global commercial operations.

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 have significantly increased our spending in 2021 to approximately $2 billion and.

We expect to continue to further increase our spending in this area to advance and accelerate our pipeline both for existing and new programs.

We are also further increasing our investment into our global manufacturing network and digital automation and AI as well as scaling up for global commercial operations.

David Muehne: 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 investment. Our announced collaborations with Metagenome and Charisma Therapeutics fall into this category. After evaluating internal and external investment opportunities, we then assess additional uses of cash.

Our second investment priority is to seek attractive external investment and collaboration opportunities to further expand the reach of <unk> technology and capabilities.

We were considering attractive opportunities that enable and complement our platform and take a disciplined approach and nobody awaiting potential outside investments are announced collaborations with another Gino me and charisma therapeutics fall into this category.

After evaluating internal and external investment opportunities. We've done assess additional uses of cash we announced a $1 billion share buyback program in August of last year, which we completed in January of this year as part of today's press release, we announced that the board has authorized a new <unk>.

David Muehne: We announced a $1 billion share buyback program in August of last year, which we completed in January of this year. As part of today's press release, we announced that the board has authorized a new share buyback program of $3 billion. Similar to last year, we provide you with a financial framework for 2022, which you will find on page 34. We have signed advanced purchase agreements for expected delivery in 2022 in the amount of approximately $19 billion and signed option agreements for delivery in 2022 of approximately $3 billion on a probabilitized basis.

Share buyback program of up to $3 billion.

Similar to last year, we provide you with a financial framework for 2022, which you will find on page 34.

We have signed advanced purchase agreements for expected delivery in 2022, and the amount of approximately $19 billion and signed the option agreements for delivery in 2022 of approximately $3 billion on a probability basis.

David Muehne: In 2022, we believe that the SARS-CoV-2 virus will evolve to an endemic phase and as a result, We expect the timing of sales to be larger in the second half of 2022 than the first half. Our total cost of sales includes the cost of goods manufactured, third party royalties, as well as logistics and warehousing costs.

In 2022, we believe that the Sars Covid two virus will evolve to an endemic phase and as a result.

We expect the timing of sales to be larger in the second half of 2022, then the first stuff.

Our total cost of sales includes the cost of goods manufactured.

Third party royalties as well as logistics and warehousing costs.

David Muehne: For the full year 2022, we expect a cost-of-sales ratio in the low to mid-20s percentage range. The increase compared to prior year is driven by an expected increase in manufacturing costs, as well as a decrease in expected average selling price per dose. The forecast increase of manufacturing costs is primarily driven by higher costs for fill-finish activities due to an expected shift from pandemic pack sizes to smaller dose and vial presentation. The decrease in average selling price is driven by the forecast increased deliveries to low-income countries.

For the full year 2022, we expect our cost of sales ratio in the low to mid 20% range.

The increase compared to prior year is driven by an expected increase in manufacturing costs as well as a decrease in expected average selling price per dose.

The forecast increase in manufacturing costs is primarily driven by higher costs for fill finish activities.

The expected shift from pandemic pack sizes to smaller dose and vital presentations.

The decrease in average selling prices driven by the forecast increased deliveries to low income countries.

David Muehne: For R&D and SG&A expenses, we 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 expect our 2022 tax rate to be in the mid teens. As a result of the benefits from foreign derived intangible income driven by our international business mix and stock based compensation deductions. Finally, regarding capital expenditures, we are planning for capital expenditures in the range of 0.6 to 0.8 billion as we further build out our manufacturing and general company infrastructure globally.

For R&D and SG&A expenses, we 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 expect our 2022 tax rate to be in the mid teens as a result of the benefits from foreign derived intangible income driven by our international business mix and stock based compensation deductions.

Finally regarding capital expenditures, we are planning for capital expenditures in the range of <unk> six to <unk> 8 billion as.

As we further build out our manufacturing in general company infrastructure globally.

David Muehne: This concludes my remarks concerning the financial performance and I now turn the call over to Stephane. Thank you, David, Stephen and Paul. Let me now share some thoughts about where we're heading. I am pleased to see how the team is executing on our product strategy. Priority number one, fine respiratory annual booster. Our LTV is already in phase three. We're waiting for our flu data to start the phase three on flu and to start the phase one on a COVID plus flu candidate, mRNA 1073.

This concludes my remarks concerning the financial performance and I'll now turn the call over to Steve Holmes.

Thank you David Steve on that Board, let me now share some thoughts about where we're heading.

I'm pleased to see how the team is executing on our product strategy product and number one pain respiratory annual Cousteau positive is already in phase III, but when he bought through data for the phase III.

The phase one on a COVID-19 physical candidate among the 10 70 free.

David Muehne: Procedure number 2, latent virus vaccines, CMVs in phase 3, now we have 5 candidates, including BZV against shingles, and more coming. Priority number three, therapeutics with a new checkpoint cancer vaccine, and priority number four, expanding our unique mRNA platform to create new medicines. As I shared in January at the J.P. Morgan Healthcare Conference, there was a big change in commercial momentum for Moderna between early 2021 and early 2021. In Arizona variant 1, both mRNA vaccines looked the same after phase 3 data, and now we see strong real-world evidence that SpikeVax has a long duration of efficacy. Hillary Clinton won with a supply constraint.

Processing of the tool latent virus these vaccines CRB their phase III now.

<unk> holiday.

Could you give you me against shingles and more coming.

The number of free fire predicts within your checkpoint cancer vaccine and broken number four expanding our unique multi platform to create new medicine.

As I said in January at the Jpmorgan Conference There was a big change in commercial momentum from within that between early 2021 and 22.

Both of them on the vaccine look the same after phase III data and then we see strong evidence that as part of that is long duration of efficacy.

We were supply constrained and now we're getting to a place we wanted to scale manufacturing. Thanks to investments made last year and are less of a constraint.

Stephane Bancel: And now we're getting to a place where we can scale manufacturing thanks to investments made last year and our less supply constraints. We have contracts with many governments around the world. But in early 2021, we had few team members on the ground in most countries.

We have contracts with many governments around the world.

But I just wanted to ask you one with few team members on the ground in most countries.

Stephane Bancel: On 5.37, you can see that SPACVAC's booster market share has increased across key markets. You can see that changing market share data from around the world where we have teams on the ground. Even in Germany, where there is a national MRNA champion, we have moved our share of the booster market from 4% in October 2021 to almost 40% in January 2021. And it is also clear that OECD countries or high-income countries have become de facto MRA markets. We have continued to increase our signed APAs to now around $19 billion.

On slide seven you can see the spike of extra boost our market share has increased across key markets.

You see that shifting market share base out from around the world, where we have teams on the ground even in Germany, where there is a national chapter M. We have more of our share of the market from 12%.

So almost 40% in January 'twenty you Antoine.

Have you just a clear that OECD countries are high income countries have become de facto and pneumonia markets.

Stephane Bancel: We also have approximately $3 billion in prioritized options. We continue to have numerous discussions with governments and NGOs around the world. For example, the current US contract has its last shipment coming before the summer of 2022. This means that, with the $19 billion plus $3 billion of options, there is currently no APS for the U.S. for the second half. Continue, and let's go.

We have continued to increase our scientists peers, who now around 19 billion, but.

We still have approximately <unk> prioritize upfront with.

Continue to have numerous discussions with governments and Ngos around the world for example, the currency risk contract plus ship coming be focused somehow 2022.

This means that in the 19 billion.

Sean There is currently no Apu mobile U S second half.

No.

As David mentioned.

Stephane Bancel: David Meachams, when we shift it to endemic, we expect to see a tonality in sex, if here we expect to see continued from our vaccination and boosting the stalonymy sphere in our first house, and a shift to boosters as a fourth-dose booster in the Northern Hemisphere in the second half of the year, similar to flu vaccine. We were pleased to announce last week a big expansion of our commercial network. From our current 11 countries where we have Moderna commercial teams on the ground, we announced an additional 10 countries. In Europe, Poland, Netherlands, Belgium, Sweden, Norway and Denmark.

We shifted to where we expect to see it in phase <unk>, we expect to see continued primary vaccination and boosting the southern hemisphere in the first half.

And the shift of Brookdale as a form of those boosts, though nobody.

Is that in the second half of the year seemingly off of flu vaccines.

We were pleased to announce last week, a big expansion of our commercial network.

From our current 11 countries, where we are from within our commercial teams on the ground, we're not an additional tank offerings in Europe , Poland, Netherlands, Belgium, Sweden, Norway, and Denmark have you in Asia, Malaysia, Taiwan, Singapore, Hong Kong.

Stephane Bancel: And in Asia, Malaysia, Taiwan, Singapore, Hong Kong. You have seen the impact of our strong real-world evidence data, coupled with teams on the ground, drive greater Moderna market penetration. I believe the STEM phenomena will happen in the STEM new market. With a direct commercial presence in these 21 important markets, we will maximize the impact of Spyvax and also have the teams to launch our planned respiratory annual booster, our latent virus vaccine, and the rest of the portfolio.

You have seen the impact of a strong real world evidence data coupled with teams on the ground drive greater market penetration.

I believe the same phenomena that we will have plenty of those new markets.

We have a direct commercial presence in the 'twenty one in both end markets with maximizing backups buybacks.

So as a team is to not find much breath away annual cousteau latent virus vaccine and the rest of the portfolio.

Stephane Bancel: That commercial coverage and capabilities will prove critical in our ability to maximize our impact on patients and the resulting value creation. We now have distributors in Central and Eastern Europe. We have distributors in Asia-Pacific, and with this week's announcement, in Latin America.

Coverage and capabilities is critical.

To maximize our impact on patients and the resulting value creation.

We now have distributors in central and Eastern Europe , where obviously, we're tucking in Asia Pacific and we just quick announcements in Latin America. We of course continue to work with <unk> to provide access to all of our team total income coffers.

Stephane Bancel: We, of course, continue to work with COVAX to provide access to our vaccine to low-income countries. Strategically, we want to create a new business model with governments around our pan-respiratory annual booster. We have started to create a subscription or service model with governments around the world.

Strategically we want great and you'll be in that small data, we've got and that's the ramp of pine respiratory annual boosts, though we're starting to create a subscription service model, we've got and that's around the world we are in.

Memoranda of understanding with the government of Canada, and Australia. We are currently in discussion with several of our countries.

Stephane Bancel: We are currently in discussions with several of our colleagues. These are 10-year agreements, for the supply of pan-respiratory annual booster. We have also spoken with UNMASS, which has signed APS for 2023, as you can see on the slide. Numerous discussions are ongoing as we speak about securing supply for 2023 for the endemic setting to protect people at risk, 50 years old and above, people with comorbidity factors, people whose jobs put them at risk, and others who simply do not want to get serious disease. As we show you the path, the field strategy for capital location.

These are 10 year agreements for.

While the supply of apartment respiratory annual booster.

We have to still go out and Matt, which have signed Ppas for you as you can see on this slide.

Can you remember the discussion is ongoing as we speak about securing supply for 2024, you probably added <unk> <unk> to protect people at risk.

You guys are identical people, becoming commodities effect all people was struck with that much risk and others with simply because that's the walk to get to your guidance.

As we shut in the past.

Further hemo capstone Acacia.

Stephane Bancel: As David said, the priority number one is and remains to invest in the company. We have this unique MRNA platform and we have $17 billion to invest, to grow our pipeline, to launch new medicine and to expand the capabilities of our platform. Party number two is to expand the platform by e-licensing or M&A as we see new interesting nucleic acid technologies that can complement and strengthen the Moderna platform. Project number three is to return capital to shareholders. After completing our August 1991 billion share buyback plan and reducing our share count for the first time, we announced this morning a new three billion share buyback.

David The <unk> number one is and remains to invest in the company. We have this unique platform and where <unk> been done got off to invest to grow our pipeline to <unk> expense.

Capabilities of our platform.

Question number two is to extend the platform licensing or M&A as we see new interesting nucleic acid technologies that could complement and strengthen them on that platform.

Breakdown before you used to return capital to shareholders after.

After a comprehensive August .

1 billion share buyback plan and we're just seeing a shutdown for a first time, we announced this morning, a new 40 billion share buyback.

Stephane Bancel: As we grow Moderna, we care deeply about building the right company, which is responsible company to its community. In 2021, 25% of doses we shipped were to low and middle income countries. We're investing in the Moderna Science Center in Cambridge and launching an AI academy. We pledge to achieve net zero carbon emissions globally by 2030. We've announced the Moderna Charitable Foundation and the Global Fellowship Program. And we announced plans to invest up to $400 million in manufacturing facilities in Africa.

As we grow mobile now we kept deeply but building the right company, which is responsible company with community.

In 2021, 25% of those easily shipped were too low and middle income countries.

We're investing in more than a science center in Cambridge, and launching an AI Academy.

With venture received a net zero carbon emissions globally by 2000 therapy.

We've announced Madonnas charitable foundation and a global Fellowship program.

And we announced plans to invest up to following I mean is it all.

In manufacturing facility in Africa, we hope to be able to announce some positive developments soon about these exciting projects.

Stephane Bancel: We hope to be able to announce some positive developments soon about this exciting project. We will continue to push the boundaries of corporate social responsibilities and share this with you. Before taking your questions, we'd like to remind you of 2022 events. March 24th will be our annual Vaccine Day. May 17th will be our annual Science Day, where we present new platform additives. September 8th will be our annual R&D Day, where we present development pipeline key updates. And today we are announcing that we'll be hosting our first ESG Day on November 10th.

We will continue to push the boundaries of corporate social responsibility and shut these will go.

Before taking your questions I would like to remind you are 25 March.

<unk> will be our annual vaccine, they're mid 17 would be annual science day, where we presented new platform <unk> September would be our annual R&D, there, where we put that development pipeline key updates and so is there one thing that would be USD or first ESG as they're on November 10th.

I would like to close by sharing our excitement about the future of our company.

Stephane Bancel: I would like to close by sharing how excited we are about the future of our company. Because mRNA is an information molecule, we always knew this would be a company with zero drug approach all along. Well, now we know which future it will be. We are passionate about our ability to have a profound impact on humanity. We believe nobody should be hospitalized because of a respiratory virus, with the technology to do that. We believe nobody should have medical consequences, short-term or long-term, because of a latent virus. We have a technology to do that.

Because mrna is an information way.

We always knew this would be a company with zero drug approved.

Well now, we know which fluctuates would be we are passionate about our ability to have a profound impact on humanity.

We believe a number of these will be hospitalized because of a respiratory virus.

Technology to do that.

Nobody who have medical consequences shutdown or lockdown because of a latent virus.

We are a technology to do that we believe we're kind of a profound impact on disease treatments with rapid hicksville <unk> gene editing programs.

Stephane Bancel: We believe we can have a profound impact on disease treatment with both therapeutics first, and then our gene editing programs. This is just the beginning. Hope you liked it.

This is just the beginning right now we'd be happy to take your questions.

Operator: We'll be happy to take your questions. Ladies and gentlemen, if you have a question or a comment at this time, please press the star then the one key on your touchtone, The question has been answered. Do you wish to remove yourself from the queue? Our first question comes from Salveen Richter. Good morning.

Ladies and gentlemen, if you have a question or a comment at this time. Please press. The Star then the one key on your Touchtone telephone. If your question has been answered or you wish to remove yourself from the queue. Please press the pound key our first question comes from <unk> Richter with Goldman Sachs.

Good morning, Thanks for taking my question outside of the flu data that we're going to see this year, we're going to get personalized cancer vaccine data as well as rare disease data could you just speak Q in rare disease.

Salveen Richter: Thanks for taking my question. Outside of the flu data that we're going to see this year, we're going to get personalized cancer vaccine data as well as rare disease data. Could you just speak to, in rare disease, what success would look like and what the regulatory path there could be? And then for the personalized cancer vaccine, you know, whether we would be able to get a sense of proof of concept this year? Sure. Thank you for the question, Salveen.

What success would look like and what the regulatory path there could be and then for the personalized cancer vaccine.

Whether we'd be able to get a sense of proof of concept this year.

Sure. Thank you for the questions Habib.

Stephen Hoge: So first, in the rare disease space, you know, it's important to recognize that these are phase one, two studies, both the PA and MMA study. And I'll speak to the PA study mostly because, as I said a moment ago, it's the one that has enrolled its first cohort and is moving forward with enrollment. So, first and foremost, we are going to be looking at safety in these studies, as you'd expect from a Phase I-II.

So first in the rare disease space.

It's important.

Recognize that these are our phase one two studies both the PAA in MMA study and I'll speak to the ph study mostly because.

As I said, a moment ago. It's the one that is has enrolled its first cohort and is moving forward with enrollment.

So first and foremost we're going to be looking at safety in these studies as you would expect from a phase one two and so one of the most important things to establish is can we continue to dose. Unfortunately very ill people children in the case of both of these studies with mrna lnp's for up to six.

Stephen Hoge: And so, one of the most important things to establish is, can we continue to dose, unfortunately, very ill people, ill children, in the case of both of these studies, with mRNA LNPs for up to six months, or even longer, if they stay on the upbring label extension. And establishing the safety of the platform on chronic dosing, repeatedly, over six to 12 months, is an important objective of that part of the study.

Months or even longer if they stay on the open label extension and establishing the safety of the platform on chronic dosing repeatedly over six months to 12 months is an important objective of that of that part of the study.

Stephen Hoge: When it comes to efficacy, again, these are early studies and small in number, as usually is the case with rare diseases. And so, I have to be careful about interpreting any of the data from the early clinical reads too concretely. But the things we'll be looking for, you know, first and foremost, we'll be looking at, at the performance of the medicines in terms of preventing clinical outcomes. And so in the case of proprionic acidemia, these will be major metabolic decompensation events or hospitalizations that do happen with some regularity, unfortunately, for those folks who suffer from these rare diseases or disease like PA. And we'll also be looking at biomarkers and so specifically biomarkers that have correlated with preclinical disease and perhaps to a lesser extent with some of the existing transplant based therapeutic therapeutic interventions in these diseases. It's important to note that across all of all these things in the biomarkers, There are not, unfortunately, validated biomarkers for these diseases because there have not yet been therapeutics approved.

When it comes to efficacy.

Again. These are early studies in small in number as usually is the case with rare diseases and so I have to be careful about interpreting any of the data from the early clinical reads to concretely, but the things we'll be looking for first and foremost.

We will be looking at.

At the performance of the medicines.

<unk> in terms of preventing clinical outcomes and so in the case of appropriate I guess edema that these will be major metabolic decompensation events or hospitalizations.

That do happen with some regularity Unfortunately for those folks who suffer from these rare diseases or diseases like P. A.

And we will also be looking at Biomarkers, and so specifically biomarkers that core.

Have correlated with preclinical disease.

And perhaps to a lesser extent with some of the existing transplant based therapeutics and therapeutic interventions in these diseases.

But it's important to note that across all of them.

All of these things in the biomarker space there are not unfortunately validated biomarkers for these diseases, because they have not yet been therapeutics approved.

Stephen Hoge: And so it'll be a balance between looking at efficacy signals early, to be fair, potential signals of improvement in clinical outcomes, and looking at biomarkers across a relatively small number of individuals. And so there will be heterogeneous disease, both genetically and in terms of their performance. Our hope is when we get compositive data that's clear, that we'll be able to then present that and have discussions with regulators, which is the second part of your question, and have a discussion about what outcomes matter most for a potential pivotal study if we continue forward.

And so it'll be a balance between looking at.

Efficacy signals early to be fair.

Potential signals of improvement in clinical outcomes.

And looking at Biomarkers across a relatively small number of individuals and so there'll be heterogeneous disease, both genetically in terms of their performance.

Our hope is when we get a composite of data that's clear that.

That will be able to present that and have discussions with regulators because the second part of your question.

And have a discussion about what outcomes matter most for a potential pivotal study if we continue forward.

Stephen Hoge: But we do believe that the things that will ultimately matter most are clinical outcomes and so the prevention of major decompensation events and hospitalizations and obviously, although the studies will be small in patient number, perhaps even hospitalization and death. So we'll be looking for those sorts of signals from our early studies, but it's important to recognize as I said a moment ago, that these are relatively small in number and we'll wanna be circumspect in how we move forward into those efficacy studies and those regulatory consultations will be based on those data and we'll provide updates when we have them, on the PCV program. As you said, we have completed enrollment in the phase two study of PCV. And we expected that PCV, as a reminder, that is a head to head comparison of Keytruda alone versus Keytruda plus vaccine.

But we do believe that the things that will ultimately matter most are clinical outcomes and so the prevention of major decompensation events and hospitalizations and obviously, although the studies will be small in patient number perhaps even population the desk.

We will be looking for those sorts of signals from our early studies, but it's important to recognize as I said a moment ago. These are relatively small in number and we want to be circumspect in how we how we move forward into those efficacy studies and those regulatory consultations will be based on those data and we will provide updates when we have it.

Stephen Hoge: And we're looking at relapse free survival in approximately a year. That data we would expect to come in the fourth quarter of, And because it is a randomized head-to-head study, I could provide a clear signal of the potential benefit of personalized cancer vaccine, versus Keytruda alone, which is obviously the standard we're going for. That data would emerge based on when we completed enrollment, announced that completion in the fourth quarter of this year, and based on that data, we would consult with regulators and obviously decide how to proceed forward.

On the PCV program.

As you said, we have completed enrollment in the phase II study of the PCB and we expected that PCB is a reminder, that is a head to head.

Comparison of Keytruda alone versus Keytruda, plus vaccine and we're looking at relapse free survival approximately a year.

That data, we would expect to come in the fourth quarter of this year and because it is a randomized head to head study I could provide a clear signal of the potential benefit of personalized cancer vaccines.

Versus Keytruda alone, which is obviously the standard going forward.

Data would emerge.

Just on when we complete enrollment announced that completed in the fourth quarter this year and based on that data.

Would consult with regulators and obviously decided how to proceed forward it's topics.

Thank you.

Yeah.

Our next question comes from Gena Wang with Barclays.

Stephen Hoge: Our next question comes from Gena Wang. Thank you for taking my questions. I have two questions. So the first one is regarding the flu data, the phase two data in early 2022. Can you be a little bit more specific on timing?

Thank you for taking my questions I have two questions. So the first one is regarding the flu data the phase II data in early 2022 can you be a little more specific on timing.

Gena Wang: And what kind of data, you think, because you're filable that without the need of a phase three trial was the efficacy outcome. The second question is regarding the one, two, seven, three, US, age 12 to seven, team in the press release. You said, you know, if they have not conclude on benefit risk profile of 100 microgram primary series, what additional data you would need to provide? And we need to provide 50 microgram data in order to receive approved. Great.

What kind of data do you think it could be viable without the need of a phase III trial the efficacy outcome.

The second question is regarding the 127 Debbie.

U S aged 12 to 17.

The press release, you said FDA has now conclude.

Benefit risk profile of 100, Michael Glen primary release.

Additional data you would need to provide and will you need to provide 50 microgram data in order to receive approval.

Great. Thank you gena for both those questions.

Stephen Hoge: Thank you, Gena, for both those questions. So, first, a clarification on the flu data. We do not believe that the Phase 2 data alone would be fileable, and that's based on, you know, previously published regulatory guidance, not specific guidance to Moderna, but ultimately we don't think Phase 2 on flu alone, which is an immunogenicity, safety immunogenicity study of approximately several hundred, is sufficient for filing. The question is, from a filing perspective, what sorts of Phase 3 studies are necessary and whether or not an accelerated approval is possible based on just safety and immunogenicity or whether we will need to demonstrate efficacy in an independent efficacy study, a Phase 3 efficacy study, prior to filing.

So first a clarification on the flu data.

Do not believe that the phase II data alone would be <unk>.

And that's based on previously published regulatory guidance on specific guidance to Madonna, but ultimately we don't think phase two on flu alone, which is an immunogenicity safety and Immunogenicity study of approximately several hundred is sufficient for filing the.

Question is from an from a filing perspective.

What sorts of phase III studies are necessary and whether or not an accelerated approval as possible based on just safety and immunogenicity or whether we will need to demonstrate efficacy in an independent efficacy study a phase III efficacy study prior to filing and those who consultations that have not yet happened with regulators, but will on the back of that phase.

Stephen Hoge: And those are consultations that have not yet happened with regulators, but will on the back of that Phase 2 data that we expect shortly. It's important to note that there are precedents for accelerated approvals based just on safety and immunogenicity in a phase three study, which would be a few thousand people. But you will always have to then follow up with an efficacy study perhaps post-approval. And so, you know, in summary, we expect to have to do an efficacy study in flu at some point.

Two data that we expect shortly.

It's important to note that there are precedents for accelerated approvals.

Based just on safety and Immunogenicity in a in a phase III study, which would be a few thousand people.

But you always have to then follow up with an efficacy study, perhaps post approval and so in summary, we expect to have to do an efficacy study in blue at some point. The question is whether or not it would be before after accelerated approval.

Stephen Hoge: The question is whether or not it would be before or after accelerated approval with a phase three immunogenicity and safety study. That phase three study would follow on the current phase two study, and we don't think that the phase two study alone is followed. We do intend, as I said previously and as I said before, to try and start those phase three studies, whether they're efficacy, safety, immunogenicity study this year. On the question of the 1273 adolescent filing in the U.S. And so, the FDA has not provided, has not completed its review of the 100-microgram adolescent primary series. And we have decided on consultation with them to evaluate a lower dose, a 50-microgram primary series dose of adolescents 12 to 17.

With a phase III Immunogenicity and safety study that phase III study would follow on the current phase II study and we don't think that the phase II study alone is volatile.

We do intend as I said.

Previously and as we've said before to try and start those phase III studies, whether their efficacy safety Immunogenicity study this year.

On the question of the $12 73 adolescent filing in the U S and so.

No.

The FDA.

Has not provided.

Has not completed its review of the 100 microgram adolescent.

Primary series and we have decided.

Consultation with them to evaluate a lower dose of 50 microgram primary series dose.

Yeah.

That lesson is 12 to 17. It is important to note that the 12 to 17 adolescent 100 Microgram primary series has been approved globally and many other markets and we believe has been administered quite broadly perhaps up to over 1 million adolescence globally.

Stephen Hoge: It's important to note that the 12 to 17 adolescent 100-microgram primary series has been approved globally in many other markets. And we believe has been administered, you know, quite broadly, perhaps up to over a million adolescents globally. And so, we'll continue to collect that real-world data as well as the observational data from our monitoring studies. And as and when appropriate, submit that to the FDA for their continued evaluation of the 100-microgram primary series.

So we will continue to collect that real world data as well as the observational data from our monitoring studies and as and when appropriate submit that to the FDA.

Their continued evaluation of the 100 microgram primary series.

Stephen Hoge: We are, in the interim, given the strong real-world efficacy data that we've seen for the spike vaccine mRNA 1273, particularly in immune-compromised populations. We are, in the interim, preparing an EUA filing in the United States for 100 micrograms for immune-compromised adolescents or those at high risk of severe outcomes from disease. Because we think the strong efficacy profile of mRNA 1273 at 100 micrograms provides a clear benefit risk in that population.

We are in the interim given the strong real world efficacy data that we've seen for spike back from only 12 months 73, particularly in immune compromised populations. We are in the interim preparing an EUA filing in the United States for 100 micrograms.

Immune compromised adolescence or those at high risk of severe outcomes from disease, because we think the strong efficacy profile of <unk> 12 to 73 and 100 micrograms provide.

<unk> provides a clear benefit risk in in that population. We do believe that 100 micrograms provides a benefit more broadly which is why it's been authorized globally, but we'll continue to work with the FDA in the U S to evaluate other potential dose sparing strategies.

Stephen Hoge: We do believe that 100 micrograms provides a benefit more broadly, which is why it's been authorized globally. But we'll continue to work with the FDA and the U.S. to evaluate other potential dose-sparing strategies, and submit that data as we develop it. Thank you. Next question comes from Matthew Harris. Great. Good morning.

And submit that data as we develop it.

Thank you.

Our next question comes from Matthew Harrison with Morgan Stanley .

Matthew Harris: Thanks for taking the questions. I have two clarifications and then a question. So first one, on flu, should we expect that when you present to us the phase two data, whether or not you'll have had those regulatory discussions or be able to talk about potential next steps in terms of what scope of phase three studies you would need? And then second, on PA, can you give us a sense of how many cohorts you think you need to see before you may be able to provide that initial data?

Great. Good morning, Thanks for taking the questions I have two clarifications and then a question. So first one on flu.

Should we expect that when you present to us the phase two data whether or not youll have had those regulatory discussions or be able to talk about potential next steps in terms of what scope of phase III studies, you would need and then second.

On <unk> can you give us a sense of how many cohorts you think you need to see before you might be able to provide that that initial data and then third just just on that.

Matthew Harris: And then third, just on the, Timing of COVID revenues this year. I believe at JPM you would talk more about first half waiting than second half waiting and it seems like that's switched and I've gotten just a couple questions that I thought would be helpful to clarify.

Timing of Covid revenues this year I believe it J P M.

You had talked more about first half weighting than second half waiting and it seems like Thats switched and I've gotten just a couple of questions that I thought would be helpful to clarify is that mainly because you are now targeting boosters for the fall or is there something else happening here in terms of the weighting of the revenues.

Stephen Hoge: Is that mainly because you're now targeting boosters for the fall, or is something else happening here in terms of the weighting of the revenues? Thank you. So, thanks, Matthew.

So thanks, Matthew I'll take the first two questions. So first on flu.

Stephen Hoge: So, first on flu, it's obviously not in our hands alone. We will, whether we would be able to connect with the FDA and get feedback back. As we all know, the agency globally, but also the agency in the United States, agencies are, have a lot going on right now.

Obviously not in our hands alone, we will whether we would be able to.

Connect with the FDA and get feedback back as we all know the agency.

Globally, but also the agency United States agencies are.

Have a lot going on right now.

And so they are there.

There may be some delays in getting that feedback. So it is not we will probably share the phase two data as we have it and we will obviously rapidly.

Stephen Hoge: And so, there may be some delays in getting that feedback. So, it is not, we will probably share the phase two data as we have it, and we will obviously rapidly consult with agencies, but we will not gate on hearing back from agencies before we share that data and our plans for moving forward. But if it's possible to get that response more quickly, obviously that will be something we'll share at that point.

<unk> with agencies, but we will not gate on hearing back from agencies before we share that data.

Our plans for moving forward.

But if we're if it's possible to get that responds more quickly obviously that will be something we'll share at that time.

Stephen Hoge: So I wouldn't expect it, the short version, of being able to have that agency feedback, but it's possible, and we'll keep our fingers crossed that perhaps the agencies can turn that around more quickly. On PA, so the number of dose level cohorts, I think it's important to say that there are sort of two features here that we'll be looking at. Obviously, the dose level cohorts, so how many different dose level or dose frequency cohorts that we're looking at in that study, but also then the duration of time on that study, because the primary objective of the intervention of the PA program particularly is to prevent the major metabolic decompensations. And so that is also something that requires time to accrue so that you can understand within an individual patient whether you've changed the rate of those recurring events. And so it's a mix of two things.

So I wouldn't expect it so the short version of.

Being able to have that agency feedback, but it's possible and we'll keep our fingers crossed that perhaps we could see agencies can turn that around more quickly on.

On P. A.

So the number of dose level cohorts I think it's important to say that there are two features here.

We'll be looking at obviously the dose level cohorts, so how many different dose level or dose frequency cohorts that were looking at in that study. But also then the duration of time on that study because the primary objective of the intervention of the Ta program, particularly is to prevent the major debt metabolic decompensation.

So that is also something that requires time to accrue so that you can understand.

Within an individual patient whether you've changed the rate of those recurring events and so it's a mix of two things I mean, I think we would probably expect to see two to three dose level cohorts, but also given the rate of enrollment that would probably also allow us to accrue approximately a year on drug for many of the early recipients.

Stephen Hoge: I mean, I think we would probably expect to see two to three dose level cohorts, but also given the rate of enrollment, that would probably also allow us to accrue approximately a year on drug for many of the early recipients. And that combination, those who've been on for a while, as well as seeing what dose escalation can achieve, perhaps in biomarkers, will be the composited data that we think will allow us to make a determination whether we've got the right dose level and whether we've got a clear indication of benefit, and obviously whether or not we're seeing chronic safety and tolerability, which we will expect.

And that combination dose who've been on for a while as well as seeing with dose escalation can achieve.

Perhaps in Biomarkers will be the composite of data that we think will allow us to make a determination whether we've got the right dose level and whether we've got a clear indication of benefit and obviously, whether or not we're seeing it's chronic.

Chronic safety and Tolerability, which we fully expect.

Stephen Hoge: And if we have that data and it feels clear, then we will move to regulatory consultation on the next step of clinical studies and obviously update all of you with that information. So not a concrete number of dose level cohorts, but more a function of both time on drug for the early cohorts and perhaps a second or third dose level cohort data that will provide us with that. And I'll turn it over to, I think, David for the third question. Yeah, so in terms of the first half, second half timing, as we've looked now at, as we move into 22, what do we see?

And if we have that data and it feels clear then we will move to regulatory consultation on the next step of clinical studies, and obviously update all of you with that information so.

On a concrete number of.

Dose level cohorts, but more a function of those time on drug for the early cohorts and perhaps a second or third dose level cohort of data that will provide us with that clarity.

And I'll turn it over to David for the third question.

Yes, so in terms of the first steps second half timing as we look now at as we move into 'twenty two what.

David Muehne: We see that the emerging market countries of COVAX have indicated that they're having a lot of challenge to absorb all the product that they're receiving through donations. And therefore, as we as we looked at, in particular, the second quarter timing versus the third quarter, we refined that outlook to be, as I described, first half, second half, and then secondly, the second half is certainly, as Stephane mentioned, we think there's going to be quite strong boost for sales that will cause the second half to be a bit higher than the first half. Thank you. Our next question comes from Michael Yee. Hi, thank you for the question. We had a two-part question.

What do we see we see that the.

The emerging market countries of Kovacs have indicated that they are having a lot of challenge to absorb all the product that they're receiving through donations and therefore as we as we looked at in particular, the second quarter timing versus the third quarter, we refine.

And that outlook to be as I described.

First up second half and then secondly, the second half was certainly as Stefan mentioned, we think there's going to be quite strong boost for sales.

We will cause the second half to be a bit higher than the first.

Yeah.

Thank you. Our next question comes from Michael Yee with Jefferies.

Alright, Thank you for the question.

Michael Yee: One was thinking about your COVID boost strategy and the three different strategies you laid out, including the bivalent, which I think is great. Can you just talk about at what point you would decide to pick which strategy that would be, and you're confident that whatever that would be, that that would be ready and able to be approved by the FDA to distribute, presumably for the fall 2022 booster season? And if that is actually the product that would be in the guidance for 2020.

Two part question.

One was thinking about your.

Colby <unk>.

Strategy in three different strategy, we've laid out including the bivalent, which I think is great.

Can you just talk about how long.

We might decide to take quick strategy that would be and youre confident that whatever that would be that that would be ready and able to be approved by the FDA to distribute presumably for the fall 2020 Q Mr season.

That is actually a product that would be in the guidance for 2000.

Michael Yee: And the second question relates to USA. I know previously you had talked about USA boosting auctions and purchases, but I can't actually remember what or where we are for USA for 2022 or for 2023, and maybe just speak to the color about that market. Thank you. Great, Michael.

And the second question relates to USA I know previously you had talked about you might say burstein op engine purchases, but I can't actually remember what where we are for USA for 2022, 23, and <unk> and maybe just speak to the color about about that market. Thank you.

Great Michael I'll take the first question on perhaps turn it over to Stephane and second.

Stephen Hoge: So I'll take the first question and perhaps turn it over to Stphane in a second. So in terms of the strategy, so the most important thing to start with, maybe, is that 1273 as a booster already exists. And so that is a booster candidate. Although we're evaluating it at a fourth dose, we'd expect to have that safety data, you know, relatively quickly in the immunogenicity data. And we've seen strong real world evidence of mRNA 1273.

So.

In terms of the strategy so.

It does.

Most important thing to start with maybe the $12 73 as a booster.

D exists and so that is a.

Stephen Hoge: And so that booster candidate is obviously something that's well known to market and could be available quite quickly. We're evaluating the Omicron specific and the Omicron containing bivalent or 214 in two studies that are ongoing right now. Now, the challenge with all of that, and I think it's where your question is going, is that when you when you're trying to evaluate durability, a difference in durability, that takes time.

Booster candidate, although we are evaluating is it a fourth dose we would expect to have that safety data relatively quickly.

<unk> data and we've seen strong real world evidence of them more than 873, and so that booster candidate is obviously, something that's well known to markets and could be available quite quickly.

We're evaluating the omicron specific and the omicron containing by the 100 to one four in two studies that are ongoing right now.

Now the challenge with all of that and I think it's where your questions going is that when you when you're trying to evaluate durability of different and durability.

That takes time and so while we're running these studies both the underground continuing bi valent.

Stephen Hoge: And so while we're running these studies, both the Omicron and Omicron containing bivalent, and we expect to have data in the first half of this year that would be one month post boost, and we could turn around and establish, we believe, the safety and the potential benefit of those boosters. And we would hope that the bivalent would continue to be the more compelling. The challenge is that it's going to be very hard to achieve six months of durability data before Q3.

And we expect to have data.

The first half of this year that would be one month post boost and we could turnaround and established we believe the safety and the potential benefit of the of those boosters and we would hope that the bivalent would continue to be the more compelling.

The challenge is that it's going to be very hard to achieve six months of durability data before.

Q3, and that's just a function of time.

Stephen Hoge: And that's just a function of time. If you boost people now, it will take time to get that day one of the one or six month durability data that we've already started to show with our bivalent vaccine. And so the question then becomes, how do we proceed from a filing perspective if we're aiming at the fall for 2022? And those are consultations that are ongoing with regulators. Now, we do have the benefit of having tested multiple previous bivalent vaccines, and we do have the benefit of being able to use the six month follow up data there to start to evaluate this potential for better durability.

People know it will take time to get that day, one of the one or six months durability data that we've already started to show with our bivalent vaccines.

The question then becomes how do we proceed from a filing perspective, if we're aiming at the fall for 2022.

And those are consultations that are ongoing with regulators now we do have the benefit of having tested multiple previous bivalent vaccines and we do have the benefit of being able to use the six month follow up data there to start to evaluate this potential for better durability.

Stephen Hoge: And so you could imagine a world where we proceed with the one month data on our bivalent vaccine showing safety and non-inferiority perhaps against the existing variants, including perhaps the circulating variant concerns known as Omicron, and that we follow up over time perhaps in, you know, the early part of the fall with data that would confirm the improvement and durability. And then we would rely on the fact that the previous bivalent vaccines like mRNA 211 had shown that benefit of durability against previous variants of concern, including some that contain some of the same mutations seen in Omicron.

And so you could imagine a world where we proceed with that one month's data on or by ballot vaccine showing safety and non inferiority, perhaps against the existing variance, including perhaps circulating brine concerns known as homegrown.

And then we follow up over time, perhaps in the early part of the fall with data that would confirm the improvement in durability and then we would rely on the fact that the previous previous bivalent vaccine like mrna to one one had shown that benefit us.

Our ability against previous variance of concern, including some that contain some of the same mutations seen in Omaha, and so it's a relatively complicated picture because we all we do believe as we've said that it is time to update the vaccine against the mutations that are currently circulating and to improve the durability against those new variance of concern.

Stephen Hoge: And so it's a relatively complicated picture because we all, we do believe, as we've said, that it is time to update the vaccine against the mutations that are currently circulating and to improve the durability against those new variants of concern. But it does run into the challenge of timing of those bivalents.

But it does bring into the challenge of timing of those families. So this consultation with regulators are ongoing.

Stephen Hoge: So those consultations with regulators are ongoing and we'll provide updates as we align with them on the path forward. That's quite different than the public health decision from governments as to which vaccines they may want to prepare to stockpile in advance of a fall booster season, which likely can proceed in parallel even without the regulatory bivalents as it has in the past as it did during the original first wave of the pandemic. So with that, maybe I'll turn it over to Stphane to talk about.

And we will provide updates as we align with them on the path forward that is quite different than the public health decision from governments as to which vaccines. They may want to prepare to stockpile in advance of the fall booster season.

Which likely can proceed in parallel even without the regulatory filings as it has in the past as it did during the original first wave dependent.

So with that maybe I'll turn it over to Stefan to talk about.

The fall in U S. Thank.

Stephane Bancel: Thank you. Thank you. Thank you, Stephen. Good morning, Michael.

Stephane Bancel: So let me maybe talk about it in two angles. The first one is, as we said this morning, in these increased APAs, we've announced that 19 billion, there is no signed APA between Moderna and the US government. So the number in there from the US is zero.

Thank you Steven Good morning, Michael So let me maybe talk about it in two in two angles. The first one is as we said this morning.

<unk> and creative Aps, we've announced 19 billion.

There is no sign that appear for between without any U S. Government. So the number in there from a USDA zero and because there is no option I know that the government has from a previous contract that you have to go out and Thats us no option.

Correctly, so zero dollars in the <unk> progress.

What is not clear today.

Stephane Bancel: And because there's no option either that the government has from a previous contract, the US government has no option, frankly. So there's zero dollar in the three billion of option probabilities. What is not clear today is what will the U.S. government decide to do for the fall of 2020. We feel like they have done in 2021, buy vaccines from the manufacturers and give them away for free, like they did for the first, second and third dose.

East West would be U S government decides to do for 2022.

We feel like we have done in 2020 , one buyer vaccines pharma manufacturers and give them a wiffle framework.

First second and third dose.

Stephane Bancel: Will it be a private market, or will it be a mix of both private and free vaccines available? Because you could see a world where if we can sell to private markets, there are private networks, and even companies that might want to procure the vaccines.

Would it be a private market would be a mix of both from private and.

Stephane Bancel: And that's a bit that is not clear to me. So this is why in a very conservative manner, because what we have communicated so far are signed APAs or options. And because the US government has zero, we did not include any of those numbers.

<unk> vaccine available.

Because if we see if we.

We can sell.

Private markets private networks, and you are a company that might want to procure the vaccine and therapy that is not why.

Very conservative mono because what we have communicated so far <unk> options.

Because the U S government zero, we could any of those numbers.

Stephane Bancel: Thank you. Thank you, Michael. Kevin, we have time for two additional questions. Thank you. Okay, our next question comes from Cora Kazma. Hey, good morning, guys.

Thank you.

Thank you Mike Kevin.

Kevin we have time for two additional questions. Thank you.

Our next question comes from Cork asthma of Jpmorgan.

Cory Kasimov: Thank you for taking my questions. First one is I want to follow up on what you were just discussing and just kind of looking beyond this fall, though. And it's kind of we think about moving into this endemic phase and how your thinking is evolving regarding the outlook for the commercial marketplace in like 2023 plus. Do you expect APAs for larger countries, be it the US or Europe or anywhere else? Or do you think you'll be doing more selling into private markets? In other words, is there a any reason not to shift away from an APA structure?

Hey, good morning, guys. Thank you for taking my questions first one is I want to follow up on what you were just discussing and just kind of looking beyond.

This fall, though and it's kind of we think about moving into this endemic phase and how youre thinking is evolving regarding the outlook for the commercial marketplace in like 2023, plus do you expect.

As for larger countries be it the U S or Europe or anywhere else or do you think you'll be doing more selling into private markets. In other words is there a is there any reason not to shift away from an API structure and then secondly, just on capital allocation recognize your priorities remained the same year and clearly with 44 programs in development.

Cory Kasimov: And then secondly, just on capital allocation, recognize your priorities remain the same here. And clearly, with 44 programs in development, new subsidiaries opening around the world, you have enough capital to do many things simultaneously. But how should we think about priorities with nearly 20% of your year end cash being dedicated to this latest buyback? Is that 15 to 20% range of kind of your balance sheet an appropriate number to be thinking about in the future?

<unk> new subsidiaries opening around the World do you have enough capital to do many things simultaneously, but how should we think about priorities with nearly 20% of your year end cash being dedicated to this latest buyback is that 15% to 20% range.

Kind of your balance sheet and appropriate number to be thinking about in the future. Thank you.

Cory Kasimov: Thank you. So let me take the first question, Corey, and I'll turn to David for the buyback question. So if you look at the countries outside the US, they are, In like the non-pandemic markets, they are mostly, you know, direct contract with governments anyway. So what is it going to look like in terms of shape and form is not very clear.

So let me take the first question Corey and.

Tons with David buyback question. So if you look at the countries outside the U S. They are.

Let's say non pandemic market they are must be.

Direct contract with garments anyway.

So what are you going to look like at them Akshay platform, even though it's very clear that putting Europe as purchase together the vaccines for a pandemic.

Stephane Bancel: For example, you know, Europe has purchased together the vaccines for the pandemic together, which is not the case, let's say, for seasonal flu, for example. So will they continue that model for COVID and move to that model for other vaccines, or will they go back to a national system? It is to be seen. But all countries like Japan, Canada, and so on have basically a single, you know, buyer market. Some countries have small private markets, but it's mostly a kind of government orders.

Which.

He is not the case at Sephora seasonal profile. Therefore, so we will continue that's more therefore copied and move more therefore over vaccines.

Back to a national system.

Used to be to be seen but all countries like Japan kind of that so basically a single buyer market. Some hopefully there's enough small private markets.

But it's mostly kind of government oil and so we are in discussions with governments about 'twenty free as you saw we have already signed contracts about 'twenty for you because some countries like the UK Nols and.

Stephane Bancel: And so we are in discussions, you know, with governments about 23. As you saw, we've already signed contracts for 23, because some countries like the UK and the world, wanted to secure supply because they believe very deeply that the endemic markets will require annual boosters and so we just want to get the hell of it. And as you saw, what's we're doing with Canada and Australia, which I think is a very interesting new model of kind of service-based subscription like partnership, is we're basically, you know, trying to secure, you know, as we said, you, And we're in discussion with several more countries about setting a similar model in their countries where we build a plant, they reserve a given volume for a year, let's say 20, 50 million dollars, 100 million dollars, depending on the market size.

I wanted to secure supply because we believe very deeply that the endemic market will require annual boost dose and so we just want to get ahead of it.

And as you saw throughout the week.

And of that in Australia, which I think is a very interesting new mosaic kind of service base subscription like partnership.

We're basically.

Trying to secure as we said you know 10 year agreements.

And we're in discussion with several more countries.

About 15 does seem a dominant in the countries, where we've been in the plants.

In Brazil.

Volume for year 2015, we have those under those depending on the on the market size.

Stephane Bancel: And then what we commit to them is to be able to customize the respiratory vaccines with what they believe they want. So as you saw from Paul's presentation, there's a lot of respiratory virus that most people are not aware of, even their name, look at PIV and very few people knew that there were coronaviruses circulating and creating so much hospitalization and death every year. Well our vision is to bring all of those components together and discuss with local public health experts on an annual basis what do they want in their vaccine for Canada or a vaccine for Australia.

And then what we commit to them is to be able to customize.

The respiratory vaccines, we believe.

Believed they want so as you saw from <unk> presentation, there's a lot of respiratory virus that most people are not aware of even their names.

Look at PID and victory knew that there were coronavirus to secretary at creating somewhat of a subsidiary Xi'an and deaths every year.

Our vision is to bring all of those components together and discuss local public health experts on a natural basis, whether they want in their vaccine for kind of where that came from Australia as we discussed on the floor in the fall.

Stephane Bancel: As we discussed on the flu call in the fall, sometimes you know WHO picks a flu strain like H3 and then it's a different flu strain that winter that is between let's say North America, Europe and or Asia like Japan and so on.

Some time ago deputy ratio of peaks of pro strength like a train.

And then it's a different strengths.

That is between let's say North America, Europe , and Asia, ex Japan, and so on and so the ability to customize and work with local public health authorities to customize a vaccine that we think is a really unique feature of this platform.

Stephane Bancel: And so this ability to also customize and work with local public health authorities to customize the vaccine they want we think is a really unique feature of this platform. So that's what we're trying to do here is to really establish very long term agreements. I am not aware of other companies having done this type of thing in pharma.

Because every two combined components and so.

So that's what we're trying to do here.

To really establish very long term agreement.

Aware of over company that we can go on this type of thing again pharma and I think it is something we can do and the teams are working very actively also.

David Muehne: And I think this is something we can do and that the teams are working very actively on. We'll have to wait a few more months to see more coming, but that's quite a lot of discussion. We just have to forget that because we cannot do, you know, 10 countries at the same time in discussions because those are very customized and very complex partnerships. But that's exactly where we're trying to head.

We'd have to wait a few more months seem upcoming but quite that discussion. We just have to wait for that because we cannot doing though tech offerings at the same time in discussion because it's a very customized and very.

<unk> partnerships.

But that's exactly where we are frankly, David you want to talk about.

David Muehne: David, you want to talk a bit about buybacks? Sure. Yeah. Yeah. I mean, I guess what I'd say about the announcement today, I think what you need to think about is a few things as we did. So, you know, why 3 billion? Why now?

Thinking about the buybacks sure yeah, Yeah, I mean I.

I guess, what I'd say about the announcement today I think what you need to think about is a few things as we did so you know why 3 billion why now it starts with a few things one is.

David Muehne: It starts with a few things. One is, as we said, investing internally and externally and ensuring that we have plenty of firepower to allow us to do that. So clearly, when we enter 2022, we're in a good position to fund all of the opportunities that we think we have, and they're very compelling. So that's one.

As we said investing internally and externally and ensuring that we have plenty of firepower to allow us to do that so clearly where we enter 2022, we're in a good position to fund all of the.

<unk>, we think.

We have and they are very compelling. So that's one two is I'm looking at what visibility we have of additional cash generation for the company.

David Muehne: Two is looking at, you know, what visibility we have of additional cash generation for the company. And, you know, again, we feel very good about that, certainly as we enter 2022. And then thirdly, we look at the valuation levels. And, you know, certainly we think this is quite attractive at these levels. So combination of all that adds up to an announcement of 3 billion. To your question, should I be filling in the model for that to continue on an ongoing basis?

And you know again, we feel very good about that.

Certainly as we enter 2022, and then thirdly, we look at the valuation levels and certainly we think this is quite attractive at these levels. So combination of all that adds up to what the announcement of $3 billion.

To your question should I be filling in.

The model for that to continue on an ongoing basis.

David Muehne: I think it's a little bit early for us to comment right now on that question, and I'd encourage you just to wait and let's see how this evolves. But we feel very good about the prospects for the business. I think the statement today is one of a strong confidence that we can achieve all of the objectives that we've set out for the company. That's helpful.

I think it's a little bit early for us to comment right.

Right now on on that question and I'd encourage you just to wait and let's see how this evolves, but we feel very good about the prospects for the business I think the statement today is one of the strong confidence we can achieve all of the objectives that we've set out for the company.

That's helpful. Thank you.

Our last question comes from Tyler Van Buren with Cowen.

Cory Kasimov: Thank you. Our last question comes from Tyler Van Buren with Caltech. Hey, good morning.

Hey, good morning, Thanks, very much for fitting me in on a similar topic of conversation can you just provide your latest thoughts on future U S pricing for Spike backs do you expect future contracts with pricing that is normalized relative to ex U S countries.

Tyler Van Buren: Thanks very much for fitting me in. On a similar topic of conversation, can you just provide your latest thoughts on future US pricing for SpikeVAX? Do you expect future contracts to have pricing that is normalized relative to ex-US countries? And maybe just on a second point to clarify, do you believe that a new variant wave emerging by year end is necessary to record the vast majority of the $3 billion in APA options? So, let me start.

Maybe just.

On a second point to clarify do you believe that a new variant wave emerging by year end as necessary to record the vast majority of the $3 billion an AP options.

So, I will not comment on U.S. pricing for obvious reasons, because of our discussions with the government. I think, as we said before, once this goes into a normal private market, we do expect the pricing to be higher. We think the vaccine does not reflect, sorry, the price does not reflect the value of a vaccine from a pharmacoeconomic standpoint. And I mean, the the the options are three billions.

So let me stop so I would just comment on the U S pricing for obvious reasons, because it's all discussions that go on that.

Yes.

I think as we've said before once these goes into a normal private market.

We expect the pricing to be higher we think.

The vaccine does not reflect sort of a private number reflect the value of a vaccine from a from a macroeconomic standpoint.

So they are just different stage. Some are just waiting funding from governments to move into fully signed APS. Some are, you know, things with COVAX that has no placeholders for future needs. So I don't think there needs to be a new variant for some of it to happen. And plus, the US on top of that, but again, we have never managed through a pandemic and through a transition from pandemic to endemic. So as always, we want to be cautious and prudent. But I think it doesn't need a new variant for a matter of a chunk of a three billion to move into signed APS.

And I.

I mean.

Options are 3 billion. So just different stage, some just waking funding from governments to moving 245 P. M.

Some things.

Things, we've coax, that's asking a placeholder for future needs. So I don't think there needs to be a Dubai fall some of it will happen.

And plus the U S on top of that but okay.

We have never managed for a pandemic that for transition from pandemic towards Amy So as always love to be cautious and put up.

But I think he doesn't need a new variant fall of motto track over freebie them to move into some of the peers.

Great. Thanks, so much.

Great, thanks so much. Ladies and gentlemen, this concludes the Q&A portion of today's conference. I'd like to turn the call back to Stephanie for any questions. Well, thank you very much, everybody, for joining us. I look forward to talking to you in the coming days and weeks and especially to welcoming you to our vaccine day, which will be exciting in March. Thank you. Ladies and gentlemen, this concludes today's presentation.

Ladies and gentlemen, this concludes the Q&A portion of this conference I'd like to turn the call back to Stefan for any closing remarks.

Well. Thank you very much everybody for joining I look forward to talking to you in the coming days and weeks and especially to welcome UFO vaccine day, which will be exciting in March. Thank you.

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

Okay.

Okay.

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And then.

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Okay.

Yes.

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