Good afternoon, and welcome to Moderna's COVID-nineteen Vaccine Update. At this time, all participants are in a listen only mode. Following the formal remarks, we will open the call up for your 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, please proceed.
Thank you, operator, and hello, everyone, And thank you for joining us on today's call to discuss new data points, including clinical data and analysis from our 1 year follow-up of our Phase 3 COVE study. You can access the press release issued this afternoon as well as the slides that we will be reviewing by going to the Investors section of our website. On today's call are Stephane Bancel, our Chief Executive Officer Stephen Hoag, our President Paul Burton, our Chief Medical Officer and Jack Collyn Miller, Senior Vice President, Therapeutic Head of Infectious Diseases at Moderna. 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 of 1995. Please see Slide 2 of the accompanying presentation and our SEC filings for important risk factors That could cause our actual performance and results to differ materially from those expressed or implied in these forward looking statements.
On Slide 3, please see the important indication and safety information for our COVID-nineteen vaccine, which has been authorized for emergency use in the United States With that, I will hand it over to Steven.
Thank you, Lavena. Good afternoon and good evening, everyone. Thanks for spending time with us. I'd like to cover a few topics today that were covered in a press release just sent out half hour ago. First, we'd like Review some of the recent vaccine effectiveness data from the real world about the Moderna vaccine and against the Delta variant.
2nd, I'd like to provide an update on some recent data from our Phase 3 COVE study looking at breakthrough infections that might inform the use of booster dose as well as immunogenicity data on the vaccine booster. And then lastly, summarize our current thinking about a booster dose. So first, summarizing some of the real momentum. Menurus COVID-nineteen vaccine remained effective in the face of that delta surge Through a median of approximately 3.5 months post completed vaccination. In fact, as highlighted in the red bottom, You can see vaccine efficacy for Moderna's mRNA-twelve seventy three that was 95% with a 95% confidence interval of 92 That real world effectiveness is very encouraging and gives us confidence that as of today, the mRNA-twelve seventy three vaccine It is really providing strong protection against all variants of concern, including Delta.
But the big question we're all wrestling with right now scientifically And the best way we can look at that is through our Phase 3 study. And that's because these the folks who have participated in our Phase 3 study are among the earliest mRNA-twelve seventy three. In fact, most of them were vaccinated over a year ago when they received their first dibs in August September of 2020. We're able to look at the effectiveness of the vaccine because we can compare those that received vaccine and vaccination, as you can see here, highlighted in blue And the early 1273 group in August, September, October against those who are originally randomized to placebo and therefore Participate in the blinded study, but yet EUA and crossover were then offered the vaccine and overwhelmingly accepted it and were vaccinated in January February this year. That creates a window, 2 different cohorts in the same study that we're following in our Phase 3, Many of whom have been vaccinated on median of about a year ago and second half we've been vaccinated on median about 7 months ago.
As we entered the period of time when Delta surged in the United States. Now As we started to look at the increase in cases of Delta in our study, as you'll note at the bottom, the number of COVID-nineteen breakthrough cases among vaccine recipients surged quite significantly from single digits to low double digits prior to June 2021 281 and 169 cases in July August respectively. So that large delta surge was Captured as vaccine breakthroughs between those two groups. And by comparing those groups and the relative risk of being in the 11 to 13 month Approximately vaccinated a year ago and those that are 6 to 8 months since their first vaccination during that surge, we can develop a view of what the impact of waning immunity between 1 year and approximately
6 to 7 months would be.
And that data was summarized in the preprint that we posted today. Now briefly, if you look at those 2 cohorts on the next slide, you'll see that at baseline heading into that risk window, they were largely the same. And so, first looking at the mRNA-twelve seventy three E cohort on the left, you'll note that there were 14,700 participants. And in the original placebo group called mRNA-twelve seventy three P here, there were 11,400 participants. The difference, approximately 3,000 participants It's made up of 2 main groups, those that had come down with COVID-nineteen prior to vaccination in the placebo group, of which there was nearly 1,000 cases And secondarily, those that decided to leave the study at the end of last year to pursue vaccination through another means, I want to be notified that they were on placebo.
But if you compare the groups across the different demographic and risk factors, you'll note that they are still substantially the same. In fact, the age group the age between the groups is Similar to 5,150, first highlighted blue row. You'll notice there are 162 cases in our original vaccination group of about a year ago and that equates to a rate of about 77 per 1,000 person years. That compares with about 88 cases in the more recent vaccination group of about the last 6 months At a rate of 49 per 1,000 person years. That actually leads to a significant relative reduction in risk.
In fact, if you look at the difference and the reduction in risk observed with being less than 6 months or 6 months approximately 6 months from your last dose of vaccine, There's a 36% reduction in risk and 95% confidence intervals as you can see are significant with a range of 17% to 51%. That is also true. If you look at the 18 to 65 population underneath, as and there's a numerical trend in the same direction, although number lower for the 65 and over population. Now as we go down, you'll also note that the numbers become smaller, but the trends generally hold. And so first looking at severe disease, you'll see that there are 13 cases of severe disease in the folks vaccinated last year, Comparing with 6 cases of severe disease and those more recently vaccinated, that is approximately a twofold increase or a 46% reduction in risk And perhaps a trend toward numerical trend toward slightly higher numbers as you move
to the 65 plus population with 6 cases of severe disease
in the older vaccination And only 2 cases in the Mauricio group. Now on the next slide, I'd like to provide a little bit of more of an overview of the severity that we're seeing across this group For context, again, all present in the manuscript. So if you look at overall per protocol COVID-nineteen cases, there were 250. And again directionally approximately 2:one ratio. There were 3 instances of hospitalization in those and all 3 were in the cohort that was vaccinated Over a year ago, and there were 2 tragic cases of death from COVID-nineteen, both present in those vaccinated in the early cohort The median follow-up of 13 months.
So overall, severe disease was present in this population and accounted in total for about 7 point 6% of the cases. All severe diseases, one present, had over 5 symptoms for COVID-nineteen with a range of 5 to 13 symptoms. The majority of cases did meet the protocol criteria based on low-two sat with a range of 88% to 93%, so hypoxia. And if you look along the severe cases, there was a trend towards greater severity in the earlier vaccination cohort. And as you'll note in the preprint, Severe cases were seen across all age groups, including in participants who do not have any known risk factors, particularly of COVID-nineteen.
So how do we estimate what that impact would look like? And what does this quantification from the Phase 3 study suggest to us? So first, the Phase 3 study does give us a direct approximation or estimate of the impact of waning immunity On protection against COVID-nineteen and allows us to estimate what the increased risk of COVID-nineteen breakthrough will be As we look forward into the future, which is the question that we're all wrestling with right now. If we estimate the impact of being greater than 7 months from your last dose In the United States, which is comparison to those 2 groups, and we extrapolate again within the United States where the study was conducted across the 66,000,000 adults in the U. S.
Who received 1273, You'd expect approximately 28 cases per 1,000 person years of exposure. That would be about 1,900,000 cases per year of exposure Or if you divide that by 12 months, that's an incremental 150,000 cases of COVID-nineteen per month That are related to what we would characterize as waning immunity. Again, all of the participants at both arms of the study were exposed, So what does that mean for us as we look forward? Now this is only one estimate and one way to look at it, but we do believe that this means as you look towards the fall and winter In the United States, we would estimate the impact of waning immunity at a minimum to be approximately 600 additional 600,000 Additional cases of COVID-nineteen. And as I covered a moment ago, although the numbers are low, we would expect some of those cases to be severe And unfortunately, some might result in hospitalization and death.
This begins to form the impetus for why we think a booster vaccine is necessary. So in the last few slides, I'll try and summarize how we're viewing the booster in the context of this data and The clinical data that we have on a 50 micron booster. So first, we do believe a third dose booster will reduce the risk of COVID-nineteen Based on the data I just presented, illustratively here, we're showing a view of what immunity might look like and again strength of immunity In the study as we conducted it, is this a surrogate for neutralizing titers perhaps, but it is not actually neutralizing titers. This is an illustrative representation. But nonetheless, you get the idea of what we believe we've now measured in the Phase 3 study, which is we have a group of participants who were vaccinated Approximately a year ago and the second group who were vaccinated at the early part of 2021, approximately 8 months ago.
Both, We believe we achieved similar levels of immunity given their similar profiles and we would have seen some leading in that immunity over time. And what we're able to do today is to take a snapshot In July August of this year, as denoted by number 1 here, and say, what's the impact of that difference in the level of immunity that was achieved as a function of time, And what we now know is that there is a significant difference between those that were 8 or 13 months from their last dose of vaccine. And we believe that that's approximately equivalent to 150,000 potential incremental cases of COVID-nineteen per month in the United States As a result of waning immunity, it's not the only breakthrough infections that are happening, but it is the delta measured by that one. Now that becomes something we hope to try and address with a booster vaccine, which would boost that immunity back up hopefully at levels that are more like Where we were immediately following vaccination. Now on this slide, I'm sharing again some data that had been previously presented at our R and D day showing neutralizing titers following the 50 microgram And booster that we've filed with regulators for mRNA-twelve seventy three.
Just quickly to orient you to the data on the slide, all of the data here has been Done in the clinically validated NIH assays, which we are very grateful for their help. And it is the data that covers both our Phase 3 study on the left hand side, an And our Phase 2 booster study, which was recently completed filed with the FDA. Now first is the Phase 3 COVE study. 1 month post vaccination, as you can see, the geometric mean titers in that cohort 1 month after vaccination was approximately 1,000 or 1081 With a very nice tight 95% confidence interval. That's the bar that we want to get back to or perhaps slightly exceed, but get back to that bar To make sure that we address the question of waning because that is ultimately what we believe fell away.
As you'll note in the Phase 2 portion, we did have pre boost titers and again this is previously presented, but 6 to 8 months after people have been vaccinated, those Titers had waned substantially down to approximately 126 and that was responded very well to boosting. And as Jackie presented a week ago, A post BOOST titer in that same booster study, 50 micrograms of 1273 as a dose 3 increased titers in all participants up to a level that was significantly Then the Phase 3 benchmark that we set ourselves, in fact, titers of 1893. And if you just look at the 65 plus sub cohort within those Roughly 300 people, 76 of them were 65 plus. And you see again the titers were significantly above the Phase 3 benchmark, even including younger healthy adults in that Phase 3 benchmark reaching titers of 1762. So We do believe that a 50 microgram dose not only achieves the objective of getting to the same level of protection that you had prior to waning immunity, But actually significantly feeds that by a factor of 1.7.
So on the next slide, if I bring us back to that illustrative picture, what we think that means is that a booster dose Given today, we'll increase the strength of that immunity, not just to levels that you had to the left of the chart, but to levels that are significantly above it, maybe perhaps 1.7 fold above it. And we know that a 50 microgram booster will be able to do that. That should counteract at a minimum the waning immunity, And we believe this will reduce COVID-nineteen cases to an even greater extent than is measured By the way, the immunity in as noted by number 1. How much greater? We can't say.
We believe there will be some benefit, But it's but it is not currently possible to give a specific answer on that number, but we believe it will be better. And that's not the only advantage of boosting. So on the next slide. We also believe that a third dose Of mRNA-twelve seventy three has a chance that it will of extending significantly extending immunity throughout much of next year as we seek to end the pandemic. It has been well demonstrated both in our prior work including with the CMV vaccine mRNA-sixteen forty seven as well as in other vaccines That a delayed booster does help refine the immune response and actually can lead to a different curve for waning immunity, so longer, more durable protection.
We do not currently have any data on what that would look like. We are going to be collecting it through our Phase 3 study, including those that just recently received their 50 micron booster In Phase 2, but also Phase 3 by continuing to study the value of any boosters. And we hope over time, we'll be able to add evidence There's more durable immunity following that 3rd dose. So overall, while we think that there is a clear benefit To the vaccine right now and continued evidence of waning immunity as we've quantified as a moment ago. We do think that there are additional benefits that can emerge with a second dose, both by increasing titer significantly above the level seen In Phase 3 and by perhaps extending the durability of immunity.
So with that, I'd like to turn it over to the operator and invite any questions from any of you about the data we've covered today or our approach to review on boosters.
Our first question comes from the line of Salveen Richter from Goldman Sachs. Your question please.
Great. Good afternoon. Thank you for taking our question. This is Elizabeth on for Salveen. So in light of your data, the real world data that's Been emerging over the past few months now and ahead of the FDA meeting this Friday.
What do you view as the key outstanding debates around the timing of booster administration? So how long after the primary series the boost is given and around the use outside of immunocompromised individuals?
Thank you for the question. It's a great one. And it's one that really I'd say is only partially directed to Moderna, Because there at the end of the day, the deployment of interventions like a booster in the pandemic really should be decisions made by public health officials, including the CDC and FDA. That said, the questions that we have or the position that we have as a company is, We do think there is building evidence already, for instance, from the Phase 3 study I just presented here that there is a benefit that we had from And not just boosting those that are immunocompromised, we already have a third dose for immunocompromised population to help them Get the highest levels of immunity, get the same levels of immunity we would hope as we saw with healthy people. But instead actually adding a 50 microgram boost to help get everybody else So maybe 6 months or later from their vaccine booster back to the level of immunity they had immediately following vaccination.
We think that's prudent this year because there is still so much circulation of SARS CoV-two virus, particularly the Delta variant that's happening right now. The pandemic is not over That we are all going to be exposed to it repeatedly and we think the risk of waiting immunity is particularly high, the risk of that breakthrough. Now we happen to think that the time for doing that It's too early rather than too late. You would rather not be too close on this thing. And so from our perspective, The data we have right now shows an obvious potential benefit at about 6 months after your primary series, 6, 7 months, give or take.
And so our filings and requests with regulators have been to consider amending the authorizations to allow a 50 microgram dose 3 Approximately 6 months after completing your primary series. And we think the day to day supports that. Now the decision of whether or not that actually happens and then if it is recommended for broad use It is not one for Moderna to make, that really rests with public health officials, but we're doing our best to make sure they have the data and the tools in hand if they choose to deploy it in that way.
Harrison from Morgan Stanley. Your question please.
Great. Good afternoon. Thanks for taking my questions. Stephen, I'm wondering if you can just talk more broadly about, I guess, risk benefit. I think when I read the Lancet Oral, I think there was a focus also on risk of a 3rd dose.
So maybe what data have you collected more broadly around Safety and rheogenicity from a third dose and how do you think about risk benefit in that context?
Right. Well, I'll maybe take a first crack at the clinical development data. And if I miss anything, I'm sure Jack you'll fill in. But then I'll I'll ask Paul to chime in because there's just so much more data that's emerged from the real world on safety and efficacy that's probably the best place to answer the question. So first on our clinical trials, We have continued to see a safety and tolerability profile of a 3rd dose booster that is consistent with the 2nd dose of our vaccine, which has generally been very well tolerated.
And we have now quite a lot of experience from our clinical trials on that 3rd dose. And as you all know and we all We'll recognize, fortunately these vaccines have been really well tolerated in mRNA vaccines generally. And therefore, the adverse events that we're now talking about are exceedingly rare in the you count them per million doses delivered And not something we will ever really be able
to see effectively in clinical studies. And that's where
we have to defer to public health officials. And I might invite Paul to come in and sort of summarize our perspective on The recent data there.
Yes, absolutely. Thank you. I think there's a couple of important studies To think about, one is, we know the data published by Victoria Hall recently in New England Journal We'll actually randomized people, immunocompromised individuals having undergone organ transplantation to that third dose and are able to carefully assess them. And we see there a robust safety profile consistent, as Stephen says, with the larger populations that we So that's I think very comforting, very reassuring. And last week as well, we saw published in JAMA By Klein and colleagues, a very nice analysis, 6,000,000 people, 11,000,000 doses looking using the Vaccine Safety Datalink.
So this is a network here run by the CDC to be able to look at cases and carefully adjudicate them And look at them. 23 different safety endpoints were identified. Crease specified Criteria for statistical significance were defined. Not one of those characteristics was met Across all of those different 23 safety endpoints. So, in the conclusion, I think we have based on the available data is This is a very safe and effective vaccine.
And with the available data we have in those other Settings that Stephen mentioned, I think we would expect the same to be seen in the booster setting as well.
Our next question comes from the line of Michael Yee from Jefferies. Your question please. Michael Yee, you might have your phone on mute. We're still not hearing you. Should we move on to our next questioner?
Yes, please.
Our next question comes from the line of Gena Wang from Barclays. Your question please.
Thank you for taking my questions. So I have two questions. First is, giving Pfizer seems to have show less effective in terms of durability And they propose 6 months. Do you think it will be a longer phase will be required for your booster strategy, I. E.
Longer than 6 months? And then second question is, do you expect Adacom for your boost regimen? We know that we will have one this Friday, but do you also But one for your booster strategy, the regimen. And then quickly, when should we expect full approval of the vaccine?
Great. Thank you, Gina, for all three questions. I'll try and take a first crack and then invite others to See if I missed anything. I don't think I should expect all 3. So first on Pfizer's lower observed effectiveness in the CDC literature and elsewhere.
I think we're probably not as guided by the fact that Pfizer had lower effectiveness and therefore is boosting at 6 months. I think what we're guided by is We have great effectiveness right now in the beta delta, but we do not want it to wane. And if anything, we think the Phase 3 data suggests to us that The last the 1st 6 or 8 months are great, but you can't count on that being stable out to a year and beyond. And so that is really what guides us to sit there and say 6 months is the right time. At the end of the day, our goal is to maintain our high effectiveness, Which in the CDC data was 92%, 95%, not wait until we fall to a lower effectiveness like the 77% or 80% that we reported in Pfizer.
We would argue that is Too late to be boosting and addressing waning immunity. The question on there are a couple of regulatory questions and I'll Of course, David, I have to defer on all of these matters to the FDA. As far as whether or not there will be an advisory committee for mRNA-twelve seventy three, Yes, we do not have any guidance on that. We'll of course be happy to participate in PADIM-one if the FDA deems that necessary. It is important to note that we are still proceeding under a slightly different regulatory framework than Pfizer.
So we are still operating under an emergency use authorization, Although we have completed our BLA filing, as you noted in your last question. And this will be an EUA amendment as opposed In Pfizer's case, they're doing a full SLA. And so it's quite logical that the FDA may be viewing the obligations of those 2 differently. But of course, we'd be happy to Proceed in any way we are asked. On the question of when to expect authorization, sorry, full approval with our BLA, We completed the filing, as everybody knows, in August, towards the end of August.
And we are actively working constructively with the FDA as we are with any global to try and answer all of their questions and make sure they have the information they need. We do not have any guidance or insight into what that time would be. I suspect They would say the same, which is that they want to make sure they do all the correct work. But I know that Our regulatory partners at the FDA are working as harder, harder than we all are. I have an incredible amount on their plate right now.
And I know they are working around the clock. And we're very grateful for all that effort and the engagement that we've seen around the BLA filing. So I'm optimistic it will happen quickly, But we recognize there are a lot of things happening right now.
Thank you.
Thank you. Our next question comes from the line of Geoff Meacham from Bank of America. Your question please.
Hey, guys. This is Alec on for Jeff. Thanks for taking our questions. First, in your illustrative example, What is the minimum value of the y axis of the strength of immunity? Just trying to get a sense as to your view on the timing of when immunity from the initial vaccination course It's effectively depleted.
I'm assuming you don't think it's as early as this fall or winter. And then can you just remind us For the supply agreements currently in the U. S, I believe it's somewhere near $500,000,000 and whether you think this would cover The 3rd dose booster, given the current rate of uptake or if an additional agreement would be needed. Thanks.
Great. Thank you, Alex. I want to go to Stephane in a second on the manufacturing and commercial question. But first on the illustrative graph, it is exactly that illustrative. And so I think You capture a fair feature of the cartoon that we didn't mean to represent.
We just we don't think it will go to 0 this fall or winter for sure. And so Please don't take the cartoon to suggest that. In fact, if you look at the data in the Phase 3 publication that we just posted in the preprint, you see very strong protection still, We believe even in those that are a year out from vaccination. And so, please let me be clear, the most valuable thing Somebody can do, we can do to end the pandemic is vaccinate the unvaccinated. Even without a booster that provides a dramatic benefit and it looks durable Despite the waning, it still looks quite substantial out to a year.
So, and the question is, is there a benefit Over and above that protection that you have from that original vaccination and when did that benefit start to become clear and what is the magnitude of that? And I think that's where we're trying to follow these And anticipate that question. 3 months ago, the answer was no, there wasn't a benefit because there weren't a lot of breakthrough cases and You would sit there and say, look, if people cross the 9 month threshold, there was no real obvious advantage or not. But two things happened. Delta emerged And that was a dramatic change in the transmissibility of that virus and therefore much more exposures.
And then the second thing that happened is we played the clock forward another 3 months. And by the time we got to about 12 months on that original vaccination cohort, you start to see and you have Delta, That should become even more significant over time. Now I don't know how much more significant, but if we imagine that there are going to be additional Surgeons of infections through the fall as people go back to school and as we all move indoors during the fall winter season, which are respiratory virus seasons that we're going Continued transmission, continued infection and that waning immunity, if not addressed, would become a more significant concern. It will, I would hope never go to 0 level of protection. And so, your question of what the origin is, I don't know.
It was an illustrative picture, but it's fair to say, there's still some protection at that point. We are mainly focused on the difference between the two groups and that was we're trying to illustrate here. Thank you for that part of the question. Stephane, do you want to take the question on whether we would need another agreement and supply?
Sure.
Thanks, Stephen. So, Alex, I think if you look at where we are, as you know, since around May in the U. S, We've got more vaccines than people wanting to be vaccinated. Thankfully, there's been a spike in the summer of vaccine use. And the 200,000,000 doses to be delivered, 100,000,000 in Q4 and 100,000,000 in Q1 Should cover, I would guess, most of the booster needs.
That is why I believe the U. S. Government I'll exercise those last options in the contract set up in September 2020 to be able to provide boosters. We should not forget That it's a bit of a complex picture because on the one hand, you have also adolescents And kids that have to be vaccinated as well with prime series, the opioid epidemic is really hard to monitor and model for us How much wastage is happening right now? If you think about it, the U.
S. FDA has authorized a fair dose already Today, I have no idea how many doses in the vial are going to be used. And I remind everybody, we are currently 10 dose per vial. And so the waste paper amount right now is tough to quantify, which is why we believe that once we get the BLA, There's maybe a certain opportunity to be able to provide the private market with the right product to be able to protect every American and to be protected. Back to
you.
Thank you.
Thank you.
Thank you. Our next question comes from the line of Michael Yee from Jefferies. Your question please.
Hi, how are you? Can you hear me now?
We can, Michael. How are you?
Very good, Very good. I had a 2 part question. What I see here is that you're saying that there is reduced efficacy between the 2 different arms Based on the timing of vaccination, I think that's clearly outlined there by 36%. My question is, what do you believe the VE or Vaccine efficacy rate is versus a unvaccinated cohort. And I think that's what people are Because even though it might be reduced efficacy, it's still very high efficacy.
And I think that that's what people are trying to struggle with. So Question 1 is, what do you think that is? Maybe the Mayo Clinic addressed that data. And then number 2 is, how do you address the idea of this Political discussion around just the idea of everyone just wants to present prevent severe and hospitalizations versus actual infections, because I feel like that's Actually the issue that's preventing people from being more enveloped with this. Thank you.
Michael, thank you for both those questions. I'm going to take a stab at the first one and maybe invite Paul to offer his As well from the real world evidence side, because this question of what is the relative efficacy of the vaccine right now as it wanes It's very hard to answer clinical trials. In particular, in our Phase 3 study, we do not have that answer because we no longer have a placebo group. And so what we can talk about here is the 36% reduction in the risk of having a breakthrough case. But 36% reduction, If it's 95% efficacy, it's very different than if it's 70% efficacy, which is your point.
And it's very hard for us To know what a reasonable control group would be here. And therefore, there is two sides to that point. One is that there There's perhaps even greater benefit to boosting than is quantified by a number like the one we're talking about today, but it's very, very difficult absent real world evidence to answer. I might invite that, do you want to Paul, do you want to take a stab at what the real evidence might suggest for us in terms of
Yes. Thanks, Tim. Michael, so I think another important paper is from Qatar, a paper by Patrick Tang When they actually are able to look at people unvaccinated and then with our Moderna Vaccine and other mRNA vaccines and what they see when you get into July is in the face of Delta and they actually Genotype cases for Delta, we see vaccine efficacy going down, effectiveness going down to maybe 75%. So the Mayo paper, which you mentioned as well, clearly shows that we're in the maybe 85 But in Qatar, exactly as you say, in the face of Delta, we're at maybe 70%, 75%. So if you take a third Cut from that, you can see that you're getting into the sort of 50% to 60%.
So that really underpins our recommendation for the booster and the timing. We have to be somewhat pragmatic. We know that 3 months ago, there were only 13,000 people hospitalized. In this country today, there's 91,000. And So we have to have a pragmatic approach to timing that is going to protect people as much as possible and really protect the health Systems here in the U.
S. And around the world.
So I think it's the idea of trying to get a range of that and not knowing. And then my second part of the question, which you might want
So Michael, this is Jackie Miller from the Development Group. And I guess you're asking a very insightful question, but I want to emphasize that Even in real world evidence, we're never going to be able to get back to the world where we have placebo controlled trials. And placebo controlled trial is really the only way to answer the question you're asking. Why is that? Because unvaccinated people are actually very different Then vaccinated people, when you choose to enter a clinical trial, you're randomized.
But when you choose to be vaccinated in the real world, that often comes with A number of very different behaviors. So for example, attitudes towards masking and congregating in large groups Inside shopping malls and the like. So the point I'm trying to make is that, yes, we still see very high Effectiveness in vaccinated versus unvaccinated people, and that should be reassuring to everyone and a Good reason to get vaccinated if you haven't already done so. But it's not also entirely reassuring in terms of waning persistence and the complex Interplay with the emergence of Delta because we know that individuals who are unvaccinated are already engaging in higher risk behaviors. Amongst the vaccinated populations, we're starting to see a difference.
And what component of that is Long term antibody persistence, what component of that is the emergence of Delta, which is a much more highly infectious variant It's really difficult to tease out. But nonetheless, maybe to emphasize your final point, certainly, Vaccination is the best way to prevent severe disease. We believe that, additional vaccinations, especially for people who may have been at the beginning of the vaccination program in the U. S. So in particular, The elderly, people with other kinds of high risk conditions that may not be covered by the current immunocompromised mandate, we believe they would benefit
I hope the A. C. I understand as
well. Yes, thank you. Yes. Just a closing thought of a political question, Michael, because it's a
great I think we're all trying to figure out, are we okay with COVID-nineteen, right? From a societal disruption perspective, from a healthcare and morbidity perspective, even from a risk of mortality perspective, Let alone the economic perspective, because we all those of us with family members that are either at high risk or those of us with kids Have all had to live with the disruption of risk of COVID-nineteen, what it means for our lives. And so I think there's an aspect of this debate, Which is playing out in real time, which is, is COVID-nineteen all of a sudden acceptable? From a Company perspective, from a product development perspective, our answer is no, our goal with the product is to prevent COVID-nineteen. And so that was the original case definition that was in our study.
And it was obviously very successful to date with 1273. We think we need to continue to provide evidence for how the product can do that, how it can prevent symptomatic COVID-nineteen that meets the criteria in the study And that's where we think a 3rd dose is necessary. If the public health debate moves off of that, it says, no, no, now we accept the disruption, economic, social Or healthcare otherwise around it. That's not for us to decide the company. That's really precise that.
But it's definitely not clear to me personally That we are yet ready to just accept an incremental 500,000 cases of COVID-nineteen and the impact that will have on our society over the next 3 months, but along the ability of people And travel, see family for Thanksgiving, all the things we'd like to do. So I personally hope we are aggressive in trying to Suppress as much COVID-nineteen as possible while the pandemic is raging because I think it's to our collective benefit.
Yes. Thank you.
Thank you. Our next question comes from the line of Joseph Springer from Needham and Company. Your question please.
Hi, thanks for taking our questions and thanks for the detailed presentation. My question is sort of related to a previous question, but Just in terms of sort of the appetite that based on your extensive clinical experience And talking to clinicians and patients and physicians and alike and KOL in the field, What sort of the temperature and the appetite regardless of what the regulatory outcome is for the booster shot for
Thanks, Joseph. It's Paul. Maybe I can just start. I mean, look, one thing we have seen this week is in the United Kingdom where the JCVI recommended with the partnership with MHRA that to the government, which was endorsed to bring out the booster shot and Indeed, the 50 microgram dose of the Moderna vaccine, both in the homologous and heterologous boosting setting, I think that speaks To the sentiment of physicians around the world, we see in other geographies as well that There is a certain fear going into winter. Governments want to protect their healthcare systems to keep beds open, to keep functioning and they know that Weighing immunity will be a barrier to that.
It will be a hurdle to do that. So I think there is well balanced Caution about what to do with waning immunity, and that a realization that boosting is a way to protect patients and to protect systems.
Great. Thanks for taking our question.
Our final question for today comes from the line of Mani Saruk from SVB Leerink. Your question please.
This is Rick on for Mani. Thanks for taking our questions. So I just wanted to touch on the development of the variant specific boosters. Would the authorization of a 1273 booster change the way the company is currently thinking about the development of the delta specific booster? And also, would you anticipate that the availability of 1273 booster would affect either the pathway to authorization for the variant And either how the trials are conducted or how regulators would look at the data.
Great. I'll try to take that, Rich, and then invite Jackie to come in if I missed anything. So thanks for the question. So first on a very specific booster, Our strategy remains that we believe that a multivalent booster is the best way to plan for the future. When it comes to the delta Specific booster, the good news is we think that the data we have so far on the prototype vaccine mRNA-twelve seventy three is that we're going to do well against delta.
That's both real world evidence data, but also immunogenicity data from the study, including papers published today, Nature Medicine. And so we are confident that the PROTECT vaccine works against Delta. We're advancing a Delta booster candidate in the clinic as we speak To make sure that we have it, if it's necessary, we don't think it's going to be necessary. But we do believe that continued expansion of our variant boosters is Important. And we think that is mostly about anticipating where the virus goes next.
And so for us that is a combination booster called 213, which is a Beta delta combination, we think it will cover all of the mutations across beta, gamma and delta that actually keep us up at night. And not because of the mono variant version of that, but because we think over time there's a risk that all of the things that made Delta so good at infecting people Could show up in a beta or gamma like stream, which is very good at hiding from our immune system. So a combination of transmissibility mutations and immune escape mutations. And the only way we can anticipate what that might look like is we take the things that keep us up at night that scare us about the current variants and we combine them in a booster. And so that's our 213 program.
We do expect that to progress fastly quickly this fall. And we would hope to have that available early if necessary broadly, although we hope it's never necessary, but if some new very scary variant emerge that could be So we are committed to continue to bring this forward. On the question of regulatory path, in general, the path for these boosters It is related to immunogenicity and safety studies. And so bridging immunogenicity study, the FDA and others have put out guidance of what that needs to look like. And those do not require thousands of people, it's more like hundreds, to demonstrate that you can provide neutralized protection against those variants of concern If they were to emerge, and that allows an opportunity for us to develop in smaller numbers at 0.1.
And 0.2, I would offer is that Not all countries are going to choose boosting. As Paul just described, the UK has already made those recommendations and moved that direction, including for 1273. Maybe the U. S. Will as well, but those are countries that are on the leading edge of the first round of vaccination and they're going to still be countries that maybe are going to be looking for boosters And have present opportunities for development of novel booster candidates throughout perhaps most of the next year.
So we don't think we're foreclosed And we don't think it's a huge risk if boosters are broadly made available in those countries that are currently 6 to 12 months from vaccination. Jackie, anything you'd add to that?
Yes. Thanks, Stephen. I think you really covered, most of it. I guess the one other thing I would say is that, just building on what she said about we're not sure if these boosters would be needed or not. I felt a lot in the I felt a lot in the last year that we are fighting a war against this virus and the pandemic.
And really the best Weapon in that war is, clinical information, clinical data. And so even if, the Delta variant, Hopefully, actually, begins to retract, as boosters get implemented. We still will have learned from this clinical development program. We will have learned about cross protection and the reproducibility of being able to Generate neutralizing responses against multiple variants. We'll have learned about, our ability to combine different sequences in the same Vaccine candidate and that really contributes to the overall strategy for combination respiratory vaccines.
And we will have learned more about dosing and administration and longer term shelf life. So I think for all of these reasons, Our continued clinical development program is really central to our strategy, in the COVID-nineteen program.
Thank you, Jack.
Thank you. And this does conclude the question and answer session of today's program. I'd like to hand Program back to Stephen Hope for any further remarks.
Well, thank you all for taking the time to speak to us today and discuss this important data. We continue to believe The vaccine our vaccine MRN-twelve seventy three has been a really important tool in combating the pandemic and the real world evidence supports it. But as we talk about today, we think there are reasons to be cautiously concerned about the future Through the winter season and boosting might be necessary for many populations and that's where we expect I hope we will go in the near future. With that, thank you for the time. Thank you for speaking
to us.
And operator, we'll end the call.
Thank you. And thank you, ladies and gentlemen, for your participation in today's conference. This does conclude the program. You may now disconnect. Good day.