Good afternoon. My name is Gregory Glenn. I'm the President of Research and Development here at Novavax. I'm proud to come to you with data from our phase I trial. It has come to our attention that a reporter with STAT News misunderstood and misreported our safety data regarding hospitalization. To be clear, there were no hospitalizations. I need to state this upfront because of this confusion. This article has been corrected and posted. What I'm going to do today is walk you through our data from our phase I trial. Let's go to the next slide. We have a safe harbor statement, which I will not read.
Let's go to the next slide. Novavax has constructed a recombinant nanoparticle vaccine, and it's illustrated here how we've done this. This, by the way, this information is posted on our PLOS ONE article cited below. We have a full-length stabilized SARS-CoV-2 spike glycoprotein vaccine. It forms a nanoparticle. The nanoparticle is then adjuvanted with Matrix-M, which is our partner in creating the very strong immunogenicity. You can see on the right an illustration of the trimer, and that trimer is then inserted into a nanoparticle.
The vaccine is a liquid formulation in a vial, and it's stable at room temperature—sorry, at two to eight degrees, as standard for vaccines that use the cold chain. So if you go to the next slide, I'd like to start with some recent data we generated in an important challenge model. The vaccine, the spike protein vaccine, is called NVX-CoV2373. We immunized cynomolgus macaques with our vaccine with the doses we're using in the clinical trial and a fractional dose. The animals were immunized twice at day zero and 21.
We then measured antibody responses prior to challenge and two weeks prior to challenge, and then the animals were challenged with live wild-type SARS-CoV-2 virus. What you see here are the immune responses on the left. You can see these are robust wild-type neutralizing antibody responses. And then the second panel, which you can see, is we have then looked for the presence of subgenomic RNA in the lungs of the animals. And you can see the placebo had clearly had virus at day two and day four. In the vaccinated animals, in the clinical doses, the vaccine induced sterile immunity.
And you can see the same phenomena in the nasal swabs. So the animals were also challenged in the nose. You can see there was presence of virus in the nose. And in the vaccinated animals, we had complete sterile immunity. This is quite remarkable. We think that this is important because this suggests that the vaccine can not only protect against the lower respiratory tract illness that is the cause of much of the morbidity and mortality to this virus, but it may also disrupt the transmission through neutralizing the virus in the nose. So we wanted to start this program with this data. And now if we go to the next slide, we'll get into the details of the phase I study.
Okay. So let's talk about the study design. This was a phase I trial. It was part of part one of a phase I/II protocol. This is a randomized, observer-blinded, placebo-controlled trial. And it was designed to evaluate the immunogenicity and safety of our vaccine, NVX-CoV2373. And the trial regimen focused on assessing the 5 and 25 microgram dose levels with or without Matrix-M.
You can see the groups here. You can see there were 25 placebos receiving placebo vaccination on day 21. Group B contained no adjuvant. It was 25 micrograms of the spike protein nanoparticle. Group C had 5 micrograms of our nanoparticle vaccine with Matrix-M. You can see Group D had 25 micrograms of the nanoparticle with Matrix-M. Group E was a single dose. It's notable that, just to remind everyone, they have the dose at day zero and a placebo dose at day 21.
It's a booster dose.
It's a booster dose, but the placebo dose was given at day 21, so in that group.
Gotcha.
What you can see here is our focus, designated by the red box here, was to look at the two doses that we thought were the most likely prospects for going forward in development. That is the 5 micrograms with Matrix-M and the 25. We are testing the hypothesis that this two-dose regimen could induce a good immune response and have a good safety profile. If you go to the next slide, the study objectives for the phase I trial were the primary outcomes, which were reactogenicity, safety lab assessments, and the immunoglobulin anti-spike IgG protein responses.
Secondary outcomes include adverse events, wild-type neutralizing antibodies, and T-cell responses. If you go to the next slide, this shows you now the anti-spike IgG in a µg/mL on a log scale on the left. What you can see here on the far left, we were able to obtain human convalescent serum from a colleague at Baylor College of Medicine. This was from subjects who were PCR positive and had relatively clinically significant illnesses. I'll give you some details in a minute on that. As an anchor for our data, you can see that we had—you can see the geometric mean titer and the scatter of the anti-spike IgG responses.
What we provided on the right -hand in the blue area is some of the details, some of the actual numbers, so you can refer to that as well. You can see convalescent serum gave a response of 8,000 approximately. The placebo, you can see on the bottom there at day zero, A0, which it says there, 821 and 835, you can see there's no responses. At day zero, the unadjuvanted two-dose vaccine provided some level of IgG.
Now, it's important to compare that with the adjuvant group, so at day 21, B21 and C21 are the comparators , and D21, you can see the addition of adjuvant to the nanoparticle gave a very robust response, and you can see that also with E21, so at 25 micrograms with our Matrix-M adjuvant, you see a marked increase in immune response. Then, going back to B35, which would be the immune response seen after the second dose, you can again compare that to the D35 with a two-dose regimen. Again, adjuvant is a much higher response, so it was very clear the adjuvant gave a profound effect.
The other thing you can see clearly is the second dose provided a more than one -log increase in the anti-spike IgG protein. And when you look at these, these are quite robust responses. You can see relative to that seen in the geometric mean of the convalescent serum with the 5 micrograms, we have 63,000 titer compared to 8,000. And so these look like very robust responses. You can see the one-dose regimen, Group E on the right, that resulted in about 2,000 to 3,000 titer. So again, you can see the benefit of the two-dose regimen. So the adjuvant effect was clear.
The other notable feature here is that you can see there was no difference between the responses in 5 and 25 micrograms. In other words, this was a dose-sparing regimen here. And you can see very robust responses with this two-dose. Okay. So if we go to the next slide, we are very grateful we are able to collaborate with the University of Maryland School of Medicine and Matthew Frieman, who is a coronavirus expert. He has an assay that's done in the BSL-3 facility for wild-type neutralizing antibody. You can see here now the results. Again, I'll start with a human convalescent serum.
Again, noting that these subjects were relatively ill and had clinically significant illnesses. You can see they had a titer of geometric mean titer of 983. Now, the patterns you saw that I described in the IgG are again evident here. You'll see why there's a strong relationship between the induction of spike antibodies and the wild-type neutralizing antibodies. Again, you can see the value of the adjuvant at one dose and two doses. You can see the value of the second dose.
The immune response goes up very significantly with the second dose. And you can see that there again is dose-sp aring. Very similar take-home messages. This is a very high neutralizing antibody. You can see the response at day 35 after two doses with the 5 micrograms, with 50 micrograms of Matrix-M gave a titer of 3,906, very robust, approximately fourfold greater than the response than the antibodies detected in the human convalescent serum that we obtained from Baylor. Now, if you go to the next slide, there's just a little more detail on this. This again, just to remind you, these are subjects who were PCR positive in that hospital setting.
And you can see that there were some that were asymptomatic, some that had quite significant clinical illness such as hypoxia, shortness of breath, cough, or clusters of symptoms that were clinically significant and required outpatient care, and then several who were also hospitalized. And you can see there's a strong relationship between the severity of the disease phenomena and the micro-immune titers. So we think that this is a very good anchor for our data for understanding our data.
We would expect that a clinically significant illness is likely to lead to the sort of titers that could protect people. And so without overstating that case, we think this is a very good anchor to understand that our immune response here is measured at the day 35 titer is quite high and is certainly in line with what you might expect to be protective. Okay. So the next slide.
As I mentioned, it's very important to see if they're in the case of these types of viruses; we want to have functional responses. Here what we're looking at is the relationship between the measurement of anti-spike IgG antibodies and functional neutralizing antibodies as we measure it in the wild-type assay. And this is quite interesting. You can see on the left, the convalescent serum; there's a very tight relationship. And the way you measure that is a correlation. A correlation of one is perfect. Correlations of 0.7 are very good. You can see the correlation here is 0.958. So very tight correlation between the measurement of a spike antibody to our vaccine and a neutralizing antibody.
Now, this on the left is from the convalescent serum from the patients at Baylor. So they did not receive the vaccine. You would expect them to have a functional immune response from a natural infection, and you see that, and it shows that our assays are detecting the right kind of antibodies. Now, on the right side, the far right, you can see our adjuvant vaccines, and you can see there's a correlation between the anti-spike IgG and the neutralizing antibodies of approximately 0.95. So very close relationship. This tells us that we have a significant portion of our antibodies is highly functional, able to neutralize the virus and presumably block the infection.
You can see in the middle, this is dose group B. They received the vaccine without Matrix-M. You can see there's still a good correlation, but not nearly as strong as when we add the adjuvant. This again is further evidence that the adjuvant allows us to induce not only high quantities of antibodies, but very high-quality antibodies, resulting in neutralizing antibodies. Going to the next slide, there is another arm of the immune system that's quite important in viral respiratory diseases. We also looked at T cells in a subset of our subjects here. We were looking for antigen-specific CD4+ T cells.
These are in subjects who were immunized. You can see the different groups, the placebo, and the vaccine alone. Group C was given the vaccine with 5 micrograms of Matrix and 50 of the placebo. We've drawn these cells now after the second immunization, looked at the PBMCs, and they are now measuring the antigen-specific CD4+ T-cell population as a % of the total T cells. What you can see in the upper left panel, as you might expect, there's no reactogenicity in the placebo groups.
The way this graph is designed, you can see what's called a Th1 response on the left and a Th2 response on the right. The Th1 response is considered to be a desirable qualitative response that could result in protection. If there's an imbalance where there's too much Th2 responses, it's felt this might lead to an adverse type of antibody that could lead to less protection. You can see in group B, no adjuvant, very little T-cell responses. In group C, where we use five micrograms with 50 Matrix, you can see very strong T-cell responses at day 28 , reflecting what we call polyfunctional CD4 cells.
It includes the secretion of IL-2, TNF-alpha, and interferon gamma, all of which are indicative of a T-cell that would be very active. Then you can see we've also tabulated any cell that has any two and any three. We do see these polyfunctional T-cells in this population, which is very desirable. By contrast, the Th2 response is quite low. We look at IL-5 and IL-13, and really quite a bit lower than what we see with the Th1 response. This is a Th1 bias response, very desirable. The magnitude is high. You can see with the 25 microgram with Matrix-M in group D, we also got a robust response, again, indicating the adjuvant is important for making these polyfunctional T-cells. Again, the control group was very low in induction of the cytokines associated with Th2.
So very robust T-cell responses, has a desirable phenotype, has a Th1 response, and this will be important as we move forward. Go to the next slide. Okay. So I'm going to now talk about safety. What we do is we look for solicited localized symptoms and solicited systemic symptoms. These are then with the way this slide is designed, you can see vaccine one on the left and vaccination two on the right. On the top, you have any detection of any kinds of local symptoms, and at the top, and you have vaccination one and vaccination two. And then it's broken down by different facets of this data.
So you can see with the first of all, the tabulation with vaccination one, the vast majority of these reports are mild or not at all. And then we have a small number of moderate reactions. You can see with erythema, which is redness and swelling at the site, are very, very low or nonexistent, and there's some level of mild and moderate pain, so very desirable profile in terms of local reactogenicity. The vaccine, the second dose, is a little higher. Again, a few more moderate events, and you can see they're kind of clustered around the local pain and local tenderness, and again, I would say with perspective of a lot of vaccines, this is a very good safety profile for a vaccine.
If you go to the next slide, these are now solicited systemic symptoms. Again, they're graded through mild, moderate, severe. These are functional gradations. These are not, of course, not treatment, as I mentioned at the beginning. Just to be clear, there are no hospitalizations in this trial, and these are patients who are reporting their functional reports after vaccination. And again, you can see the vast majority of the reactions that we recorded are mild or nonexistent. There are some moderate, and there are very scattered few that are considered severe, which would mean that this would disrupt the activity of the subject.
And so you can see on the right a slightly increased level and severity. But again, remembering this is a placebo-controlled trial, you can see a number of placebo events reminding you that the second dose of the 25 with Matrix at the bottom is also placebo. So we see a number of placebo events, including a few severe events. This suggests that these are really sporadic and no particular pattern in terms of adverse events. We do expect there will be some level of adverse events such as headache and myalgia. And we do see that here. Again, overall, it's our assessment this is a very good safety profile for the vaccine.
Go to the next slide. Just to summarize, we do see a dose-independent response. Both dosage levels induced high and comparable levels of IgG. It's dose-varying. You could not, and I'm sorry; there's a little error there. This response appears to be the same for five and 25 microgram. For a vaccine like this, it's going to be deployed. This is very convenient. This allows us to extend the supply of vaccine enormously by using such a low dose. We did see IgG responses that were compared favorably with those from convalescent serum for people who really had quite an important clinical illness. And the adjuvant was required for the optimal response.
We did see wild-type neutralizing antibodies that were numerically superior to convalescent serum, which is encouraging. Both dosage levels induced high and comparable wild-type neutralizing antibodies, and we did see a 100% neutralization seroconversion rate after the second dose. Again, that's very important not to have people who are essentially left behind and don't have neutralizing antibody responses after the vaccination, and again, as I mentioned, the response and neutralization response is tightly correlated with IgG. That's a very desirable feature of a vaccine.
We did have a strong T-cell response. They're multifunctional CD4 T-cells that were induced. They're largely the TH1 phenotype, and we had reassuring safety. We had no serious adverse events. That means no hospitalizations. All the unsolicited events were mild or moderate, and the local and systemic reactogenicity was not dose-limiting, and we think generally well tolerated. Okay, and I think with that, we're going to turn to questions.
I'll let Paulie do that.
Okay.
This is Stan Erck, CEO, and Greg. Thank you very much. That is a presentation that you've spent a lifetime getting ready to make, and it's really a big deal. We've completed the phase I trial. I think that we can say that we couldn't have asked for a better profile of a vaccine for a pandemic, particularly in the timeframe that we've done this in, and so the Novavax team has done it, and we've got a good safety profile, as Greg just mentioned. We got all the immune responses that we could ask for, particularly in a phase I trial, so where do we go? The pandemic rages on. We work 24/7.
We've got two sets of tasks now before us that we've been working on. The first is, actually, we typically do this after you get your clinical data, but we're trying to figure out how to make vaccine at super large scale globally, and we're doing that. We have now started production. We started tech transfer and production in over seven countries of both the antigen and the adjuvant and what they call fill and finish packaging of the vaccine globally.
We're doing it in Europe. We're doing it in India. We're doing it in the U.S., and we're doing it in Asia, and so that is going as fast as humanly possible so that we can make a target, which is to have tens of millions of doses available toward the end of this year and 100 million doses available early in the first quarter of next year in the U.S. and a similar amount in Europe, and that's our goal.
We have ambitious goals for capacity for 2021. And we think we can make somewhere in the order of one to two billion doses of vaccine in that time period. Then we have to show that we have to extend these results that we got in phase I and we take it into phase II trial as soon as possible. We delivered these data to the FDA yesterday or today. And the FDA will look at them and give us feedback and a thumbs up on proceeding into a trial of approximately 1,500 people in the U.S. and Australia, which will extend these results into the older adult population and expand what we've done in the 131 people in this trial.
A nd in parallel, we are making plans for global trials that show efficacy. And so our goal is to have efficacy trials in multiple countries and with the target of getting into our first efficacy trial by the end of September. And we'll keep everybody posted on the details of those plans as they become clearer to us, both for the manufacturer and the clinical development and the ultimate licensure of this product on a global basis. So with that, I'd like to turn it over for Q&A.
Yes. At this time, if anyone does have a question on the phone, you can press star, then number one on your telephone keypad. Again, it's star and then number one. And we do already have some questions that have come into the line. Our first question is from the line of Eric Joseph from J.P. Morgan.
Hey, guys. Thanks for taking the questions, and congrats on the data update here. I guess the first question is, to the extent it's possible, there's going to be a lot of interest in being able to draw comparisons across the competitive landscape. And I appreciate that there are different little differences in the particular assays used to look at neutralizing antibody titers.
But to the extent that's possible, can you sort of characterize your convalescent serum samples here in terms of titer and how that sort of establishes the bar that you're —what that represents as a bar that you're referencing to when looking at the activity of your candidate being somewhere around three to four times more potent? And then secondly, as we think about the phase II study design, can you just kind of give us a little bit more color on sort of the doses that are being moved forward there and at what point in follow-up you think you'd be able to advance a dose into the phase III? Thanks.
Thanks, Eric. I appreciate the questions and the interest. So yeah, so I think we, like all the companies, have attempted to anchor their immunogenicity on convalescent serum from humans that have been collected in different settings. And the rationale, as you can appreciate, is that generally speaking, in the context of viral infections, there's an expectation that an infection that's clinically significant should result in immunity. In fact, if you have someone who's really sick, it kind of defines the ceiling of what might be achievable.
And so we were able to collaborate with Baylor College of Medicine, who was obviously being overwhelmed with subjects. And we were able to obtain the clinical history and ensure that they were PCR positive and serum samples that would allow us to assess the immunogenicity. Frankly, this process has all moved very fast. I know all the other companies and investigators have struggled a bit to obtain convalescent serum. One reason is that most of it's being used as plasma for therapy, and we were able to do this, as I said, through Baylor College of Medicine, so we, frankly, didn't know where this would fall out.
We knew that we had clinically significant illnesses, so we felt that was important and identified the serum. We were, I'd say, gratified to see that, in fact, there was a good relationship between the severity of the clinical outcomes that we'd collected and the titer, the neutralizing titer, which fits with, I would say, the normal scientific paradigm of recovery from a viral infection, so I think it's a good anchor. It's in the same assay. Our assay, by the way, is conservative. It's a wild-type assay. It's 100% neutralization.
Obviously, all this is done blind at the University of Maryland. We're very gratified or have a lot of gratitude that they were able to do so much work for us in such high quality and get such clear answers. And you can see, if you look at the slide there, slide 10, if you wouldn't mind putting that up or if you can't see it, slide 10 has the geometric mean. And it really sits at the top of this set of convalescent serum. And so again, it looks like we've really pushed the immune response to a good place with these neutralizing antibodies. So that's gratifying. I missed. Sorry, help me out with the other piece of the question.
phase II.
Oh, phase II. So yeah. So just to be clear, as Stan mentioned, this data has been delivered to the FDA for review. That's going to their review. We believe it should be very positive. It will then be important for us to then kick off the next stages of our trials. Our phase II trial is slated to, so as you can see here, we have a really convincing answer on dose and that the five micrograms is going to be the suitable dose to go with. And so, however, these are healthy young adults or 18-59, not exactly young, but maybe they can still play soccer. So it's important to extend our data, our safety , and immunogenicity data into older adults. And we felt it was wise for us to use the higher dose.
We're having a small set of subjects who are going to receive the 25-microgram dose again in the older adults just to confirm this result that five micrograms is the dose going forward, but for our planning purposes right now, this is such good data and so clearly superior that we are, in fact, planning to use the five-microgram dose in our healthy studies.
A follow-up, if you don't mind. I guess given that you don't have a dose-responsive relationship from five to 25 micrograms, appreciating your point about the safety profile here being your comfort with the safety profile, I'm still curious to know whether you'd see any need to evaluate perhaps a lower dose, a lower aggregated dose in the phase II?
Yeah. So what you see here is you see the evidence that we're at the top of a dose -response curve. So we're still at the maximum dose that the immune response can be achieved with this vaccine and formulation. So clearly, it's possible we could go down in the dose. Now, we're on a very fast trajectory out to clinical trials. So we may investigate this in one of our trials by going down in the dose. And that would be, of course, another positive thing to see that we could further dose spare. You may have seen in the primate study, we used a fractional dose, which is something we wanted to know about. And again, in that study, we saw sterile immunity. That was the one.
There was one very low titer virus in one animal in that study with the fractional dose. But it was half matrix, half the matrix dose of 25, and then half the nanoparticle dose of 2.5. And we still saw a very robust response. So we think there could be room to explore down. However, we're on a very rapid trajectory. We've got to make some assumptions today. In fact, we made this guess that this would be likely two months ago based on our non-human primate preclinical data and our previous experience with Ebola. And it looks like we chose wisely. We felt there would be likely to be dose sparing. And we're very glad to see it so clear in terms of the fact that the 5 and 25 really are hard to distinguish.
Great. Thanks for taking the questions.
Thank you.
Our next question comes from the line of Charles Duncan from Cantor Fitzgerald.
Thank you. Thanks, Stan, Greg, and team. Congrats on a great result from our perspective. Wanted to ask you a couple of questions. So first of all, with regard to convalescent serum, I'm wondering if you could provide any additional color on the clinically significant disease and perhaps look at at-risk patient population beyond just age. So do you have any additional insights that you can make on the comparison? And then secondarily, with regard to the clinical results, you did study a little bit broader sample in terms of age, up to 59-year-olds, and some of the other data sets that we've seen. And I'm wondering if you had any data from some of those older patients, say 55 to 59, in your sample set.
Yeah. Thanks. Good question. So we haven't stratified by age in the analysis. So we unblinded last week. So that would be a kind of exploratory analysis. And I'll take that up. That's an interesting thought. As you know, we have recently unblinded a phase III pivotal trial for influenza. And that is focused on the older adult population, 65 and above. So we have a lot of experience with our safety and the immune responses. As you know, we met all eight co-primary endpoints. Every secondary endpoint, we had a significant result. And the exploratory endpoints, we saw great T cell responses.
So actually, the agency will allow people to bring some of that experience to bear on the current product. So they're looking for a platform like this. And if you have that kind of data, I think that's going to be relevant. So that will help us extend into this older adult population. So we're very confident that we can induce a good response, a good T cell response, and a good antibody response in older adults based on our experience in phase I, phase II, and phase III with our NanoFlu, which is obviously a very similar platform technology. So just breaking this down a little bit more in terms of the convalescent serum, the guys on the top are the ones that were in the ICU.
There's a cluster in the middle. These are people that were ill, and they had really , actually, syndromes that you would expect to essentially be moderate COVID disease in a clinical trial. So they had cough, fever, shortness of breath, and hypoxia but just were not sick enough to be hospitalized. And then we had a smattering of a few asymptomatic subjects. And you can see some of them had titers. And you know that story.
But of course, you can see the immune response. The way this assay works, you start at a dilution of 20. So you see all those dots at the very bottom. Those are no neutralizing antibodies. That just is the place where we actually start the dilution of serum. So there are a few people in the convalescent serum who had no detectable antibodies by that measure. And you can see also, if you look back at the IgG, it's a very concordant story. The neutralizing antibodies and the spike IgG really go together very nicely. Again, more severe have a higher spike in IgG. And I showed you the correlation. So I will tell you, there's a lot of work that goes into establishing good measures.
We think our measures of immunity are extremely sound. We've worked hard with our collaborators to make sure that data was good. We've been gratified. We really saw a very reliable picture on sort of the quality information that came out of our collaborators at the University of Maryland School of Medicine, so we're quite confident this is really good data. We know these are really very good functional immune responses, and it's our view that this trial has been a fantastic advance forward for a pandemic vaccine.
Yeah. That's very helpful, Greg. We definitely appreciate substance over speed. One quick question regarding the phase II and timing of it versus the phase III. I guess I'm wondering if you see the phase II data with a little bit older patient population or sample to be enabling for the phase III. Is that a nice -to-have? Is it a need to have? Or could you anticipate actually starting the phase III before you got the phase II results with that little bit different sample?
Those are great questions. So all issues that we discuss with our partners at Operation Warp Speed, I will tell you right now, the plan is to extend the safety data in adults over 60 and over. That data can be collected fast. Then we'll use that. Again, it's going to be an interim look at the data. And we'll use that to allow us to move into the broader population for the phase III trial. So I think we're on track to do that soon. And we think that'll be an important part of what will trigger the phase III trial.
Excellent. Thanks for taking the questions, and Godspeed on the future progress.
Thanks for your support.
Do you have more questions online now? The next question comes from the line of Mayank Mamtani from B. Riley.
Thanks for taking my question. And I appreciate you putting out this data in such a tight timeline. Also helpful clarification upfront on the safety around hospitalization. So good to lay that out. So two questions for me quickly. So Greg, as you think about the older population and you think about the adaptive immune response, obviously you talk about CD4 and Th1. What other elements do you think, like CD8 T cells also, that you may or may not have yet? Could you comment on that just broadly as you think about the older population?
Yeah. So that's really good. So let me just hearken back. As you know, the flu vaccine, the seasonal influenza vaccine, where the results were very good. One of the features we have there in immune senescence is an almost absence of antigen-specific T cell responses. Matrix-M is a very good adjuvant for inducing CD4 and CD8 responses. And so what we're seeing today, CD4 responses, is not just important to show that it has a Th1 phenotype. I would say more importantly, we know that these cells are involved in enhancing the antibody maturation and maintaining durability of responses. So this T help does, in fact, manifest itself as better and longer antibody responses. It's really critical.
And we know that that could be a real issue with the older adult population. And so we expect that our Matrix-M adjuvant will generate very robust T cell responses, CD4 polyfunctional T cell responses in that population. Now, we know that CD8 responses in our animal studies and again, in our preclinical paper, which is posted and out there under review, we do show we get very robust CD8 responses. Today, we're showing some preliminary data. We expect to bolster that and pursue showing the CD8 responses. It's a little more technically difficult. When you do that in mice, there are very narrow genetic backgrounds for their MHC class I pockets.
So with genetically diverse humans, it's a little more involved. But I think in the future, we will be able to show CD8 responses. And just one other comment. We just provided the scatter plot. You can see the magnitude of these responses are really quite robust compared to what's been reported out there. So we're very happy with these responses. These are in a small subset of subjects. And we're continuing to expand on that data. So I think you want a vaccine that does recruit both arms of the immune system, both the T cells as well as the antibodies. And you can see here, we have a very good profile.
Again, that's why we're very buoyant about this vaccine because it looks so promising. And then I would say that today, our challenge data has looked very good. In fact, we see sterilizing immunity, which is really encouraging in more than one animal model. And so again, prospects for a vaccine that really has good efficacy seem quite high. And we're very eager to get out into the phase, the efficacy studies.
Absolutely. I mean, the volume of evidence to date across mice, baboons, challenge studies, and this look fantastic. Just quickly on the five -microgram dose, if I may, a two-part question there. Can you comment on the reactogenicity that you saw here, maybe relative to the NanoFlu, which also looked pretty good? Just kind of observations since the Matrix-M adjuvant is kind of the common denominator.
So if you could comment on that. And then it definitely seems like a sweet spot where you've landed with this lower dose. If you could comment on the scalability of this and what is specifically your assumption? You've said 100 million doses by the end of the year. Does that include an assumption of five- microgram? Or is it a dose higher when you think about delivering on that dose goal by the end of the year?
No, that's standard. My forecasts were based upon a five microgram dose, and so that's the most likely dose that we're going to go forward with. As Greg said, we will evaluate at some point in a future trial, and probably not too distant a future, at least an arm that tests the level below five micrograms to see if there's a smaller dose available than that, which obviously automatically expands potential capacity, so we'll look at all of that over the coming months.
Greg, any?
Yeah. Of course, we are using the baculovirus insect cell system. That's the basis of two licensed products. I think we have the nanoparticle and the Matrix-M really are the culmination of years of thinking and work to come up with an ideal vaccine platform. But it is the manufacturing is based on a well-established manufacturing platform. And so I think it's given us confidence. And having doses varied is really convenient. It's given us confidence that we can, as we scale up and make a lot of doses.
Any color on the reactogenicity of what you saw in NanoFlu versus?
Yeah. Yeah. NanoFlu in older adults, I think when you get into older adults, things quiet down a little bit. Again, their safety profile was compared to the Fluzone High-Dose, where you really couldn't distinguish the reactogenicity between the Matrix-M adjuvanted nanoparticle vaccine and Fluzone High-Dose. So I think we're giving a lot of detail here. But you can see that there's a lot of subjects who report no reactogenicity. I'll point out some of the really positive things. You can see there's almost no fever. We had one subject who had a very low-grade fever.
So that can be a very difficult thing to have in a trial when you're out in COVID. So our view is the reactogenicity looks quite good, mostly mild to moderate. Frankly, most of it mild to nothing. So that as a profile for a vaccine is really quite good. And given the fact that we are so immunogenic in terms of the immune response, I think together this is a good profile. And as I mentioned, the fact that it's a two to eight -stored liquid formulation is also very attractive. So we're celebrating. We think this is a tremendous result. We're eager to get the FDA's view on this. We have, I think, a very positive outlook.
A lot of people that we work with in terms of scientific advisors, etc., they're looking at this. I saw with some gratification that Ed Belongia, who's a very experienced vaccinologist at Marshfield Clinic, he's an expert in these respiratory diseases. He was impressed with the data. And I know him from social meetings, etc. When he's impressed, you know the data must be very good. So we're extremely excited about this data set.
It's great to hear. Congrats again. And look forward to more updates. Good luck to you.
And we do have one more question on the line currently. Before I get to this question, anyone else have this question? Star one, once again, star one for any other questions. Next question we have online comes from Seamus Fernandez from Guggenheim.
Great. Thanks. So I guess the focus of my question, I think most of the questions have been asked, but one that hasn't really been addressed is distribution. Can you just talk a little bit about, as you progress towards the broader manufacturing capabilities, what your storage conditions are and what you envision as some of the complexities?
And then separately, just on the commercial side, as we think about the potential for additional negotiations, we know that you have the sort of robust plan and agreement with BARDA. But expanding beyond that, where do you see the opportunities to kind of add additional capabilities? And would you anticipate needing any distribution partners in that regard? Or is this something that Novavax is prepared to distribute and handle on its own? Thanks.
Yeah. Thanks. This is Stan, so one of the highlights, I think, and distinguishing features of our vaccine is that it is stable. We've got data that says you can store it at room temperature for days, perhaps weeks. It has long-term stability as much data as we have because you can't have too long-term stability if you're only working on it for six months, but two to eight degrees, it looks very stable. This is really important. I mean, it's important in a normal commercial vaccine, but in a pandemic global, think of being able to distribute it worldwide with using the established cold chain, and it's formulated as a liquid.
We are co-formulating it, the adjuvant and antigen, so it's a single vial. All the characteristics of a vaccine for a pandemic are contained in this product profile, and so we're really, really happy about that. I think the people who have funded this program, like Operation Warp Speed and CEPI and the Gates Foundation, really appreciate the character. And maybe it's not unique to our product, but it might be. And so we're very happy with that. Going downstream to your question of how are we going to get it distributed globally, we're going to have partners. And as I say, we're trying to manufacture it. We've got seven different countries going right now.
And there's the process of getting the antigen and adjuvant made at a large scale and then find fill-finish capacity in many, many different countries globally. And we'll seek out partners. Once we make the product and deliver it to the U.S. government under our contract with Operation Warp Speed, that will be distributed under established vaccine distribution systems.
Ultimately, we'll get past the pandemic period in the next however long, whether it's a year or two, and we'll get into a commercial distribution system that we'll have to yet define as we try to commercialize both this product and, frankly, our flu vaccine down the road. So we're going to be the respiratory vaccine company of the world, so.
And maybe just as a follow-up question, would you mind just providing an update? And I know this is a little off topic, but other efforts beyond flu, I know that you've proceeded on the RSV side to some degree. I was just wondering where we would see additional vaccines, other catalysts moving forward. I know you guys are well in the weeds on COVID-19. And thanks for that, of course, from all of us. But just love to know about some other catalysts as well. Thanks.
So we actually got everybody who has followed the company knows that we had two phase III programs in RSV, one in the older adults and one in maternal. In my view, both of those vaccines worked quite profoundly. We dropped hospitalization from pneumonia in kids globally by 50%. Nothing else has ever done that in the first year of life. And we also had an effect in the high-risk older adult population. So I think those are two vaccines that we could go back to.
We could restart those trials with maybe a bit of a different design. U se our Matrix-M adjuvant, which we didn't use before. And so those are two very high unmet needs. So look at the respiratory world. You've got RSV, you've got flu, you've got COVID. And then, of course, we have to be ready for down the road new pandemic threats. Ultimately, there's an opportunity to combine these vaccines and have a combo available vaccine with flu and COVID someday. There's lots of opportunities. We're not a one-shot shop.
Yeah. You may have seen we published our RSV phase III trial in the infants was published in the New England Journal of Medicine last week. So there was, I think, a good outcome, great vaccine.
Yep. Well, again, congratulations on these data and look forward to seeing the phase II and the phase III advancing.
Thank you. Thank you very much.
And we do have one last question in the queue. This is from the line of Vernon Bernardino from H.C. Wainwright.
Hi. Thanks for taking my question. And congratulations on the results. You give hope that we could have a safe vaccine next year. And that's really something to celebrate. Question I had is, will you be expecting to continue to follow the Matrix-M adjuvanted subjects who were given 2373 as far as their antibody levels? And I was wondering if you could remind us if you did follow and if you could remind us the antibody levels in the non-primate challenge studies, what the antibody levels were afterward. And that's it.
Yeah. Thanks. Hi, Vernon. Good question. So we will follow up on the phase I subjects for safety out to a year. And we'll have several blood draws to look at the immune kinetics. Right now, everyone's going to be interested in durability. We don't have a lot of data on that because everything is fairly fresh. But we have a couple of primate studies where we're going to look for the long-term immunogenicity. I would say this is very reminiscent of our Ebola vaccine. From an immune standpoint, the immune system doesn't care whether it's an Ebola glycoprotein or a COVID glycoprotein.
So in that context of that development program, we did follow subjects out to one year. And we measured immune responses out at one year. We had done work on the Ebola vaccine like this. The ELISA using the IgG to the GP protein was associated with protection, and in fact, a titer of around 5,000 was, we found, to be protective. We could see in the humans at the end of the second dose, we had 50,000. And now at one year, it was 5,000. So we see persistent responses, and that's going to be a topic of a lot of interest. One thing I would say, as Stan mentioned, we are of the view this virus is not easily going to go away.
And there probably will be an appetite for boosting schedules, and so that is completely something that's up in the air. But we can demonstrate by this trial that the vaccine is boostable, which it could be a very important quality for a COVID-19 vaccine. So nanoparticle Matrix-M has that feature that you can boost. I think that's a very desirable feature.
No other questions. Thank you at this time.
All right. So this is Stan. Let me wrap it up. Thanks everybody who stuck around for this amount of time. We couldn't be more excited about where we are. We've been working for this day for the last decade in trying to get vaccines against emerging infectious diseases. This one became very apparent as recently as late January and February that this level of effort was going to be needed.
We worked our way through the mice and the non-human primates. And now we've got our first human data. Everything is consistent. All the studies are consistently showing that the vaccine has the power to prevent COVID disease. And so we're going to be working as hard as we can to continue this into efficacy trials and ultimately where it needs to be in the marketplace. So thank you.
Thanks, Jim. And that does conclude today's call. Email now.