Hello, everyone, and thank you for joining us. It is my pleasure to welcome our next speaker from Vaxart, Steve Lo, CEO. Vaxart is a company focused on oral recombinant vaccines with a proprietary delivery platform. In July, you announced top-line data from Sentinel safety cohorts from your phase IIb clinical trial, and also modification to your BARDA contract that enables the continuation of that study. We are looking forward to the updates, and Steve, welcome. Thank you for being with us, and the floor is yours.
Great. Thank you. Thanks to H.C. Wainwright for the opportunity to present at this week's conference. I am Steve Lo, and as we were just told, we are working on oral vaccines here at Vaxart. As a reminder, I will be making forward-looking statements during this presentation. Some takeaways that I want you to have for our presentation today is, number one, that we do have a very interesting and innovative oral vaccine platform. It is modular, and we are working on three important indications, COVID-19, norovirus, and flu. On the COVID study, as just mentioned, we are fully enrolled. It is a BARDA U.S. government-funded phase IIb study. The overall study will read out in the first half of 2027, but we have already been able to announce safety data from our Sentinel cohort of 400 subjects recently.
In that Sentinel cohort, there were no vaccine-related SAEs in either arm, but also lower number of AEs in the Vaxart arm versus the competitor. As a reminder, this asset is already partnered. Our partner is Sanofi. Sanofi holds a worldwide license agreement to, if they opt in, this company, Vaxart, will be eligible for up to $670 million in milestone payments and royalties, and we are delighted to have a partner in Sanofi with their significant presence in vaccines. On top of that, we are also working on norovirus. This is a great opportunity because there are 22 million U.S. cases per year. The healthcare economic burden is over $10 billion, and there are no current approved vaccines in the marketplace.
We have been on this journey with norovirus, and recently, we have a second-generation norovirus vaccine construct that we have been able to show improvement over the first generation, which I will go over shortly. As a reminder, our oral pill vaccine is thermostable. It does not involve any cold chain storage, no needles, and you do not have to go in the clinic to get an injection. We have already dosed 3,880 subjects across all of our studies with a very benign safety profile. Also as a reminder, especially as we are working very closely with the U.S. government, our manufacturing is based in the United States, and our headquarters is in South San Francisco, where our manufacturing facility is. Our vision at Vaxart is to transform how vaccines are delivered.
And if you think about, certainly this audience, the last time you had a vaccine, the amount of time and effort and involving a healthcare provider to get your injection, our vision is one day to transform that. Essentially, you may not even have to leave your house. The vaccine could be dropped right at the doorstep of your house, and I am sure with more innovation, even a drone could deliver the vaccine to your doorstep. That is certainly our vision and why the employees of Vaxart are working very hard to reach this goal. On top of the convenience, our oral vaccine platform also elicits both systemic and mucosal immune responses. From a scientific standpoint, we also believe that this would induce a broader protection.
If you see here in this graphic, we have a very unique modular platform where you can take your vaccine of choice, your antigen, and in this case, we are working on norovirus, SARS-CoV-2, or influenza, and it is put into our recombinant Ad5 delivery vehicle in our platform. This oral pill dissolves in the intestine, and it activates the immune system. This allows the protein of choice to then respond in a way where you have both a systemic and mucosal response. You see this with the fact that unlike injectable vaccines that only induce a systemic IgG, our platform generates both the mucosal and systemic response, where you have protection not only systemically but at the point of entry.
From an IgA response, mucosal IgA response, as an example, your protection could be at your nose, and this allows for greater coverage, cross-reactivity, and this is certainly something that we are wanting to prove even more with our current study. In terms of a summary of why we believe that our platform will revolutionize how the vaccines are delivered, on the left-hand side, this is your typical traditional injection vaccine, systemic immunity only. Our oral pill vaccine platform, both systemic and mucosal immunity. From a safety standpoint, certainly if there is no injection, there should not be an injection site reaction. We will show that shortly with our COVID study information. Ours is a benign safety profile.
Administration, still need, with an injection, a healthcare provider to provide that injection. With ours, self-administration, and then finally, if you think about just the logistics standpoint, no cold chain storage, a formulation that can be transported from a logistics standpoint. Definitely advantages with our platform. Here are the key programs that we are working on. As I mentioned before, from an enteric vaccine standpoint, we have a norovirus second-generation vaccine that is ready for phase II, so either investment or partnership will move this along to phase II. From a respiratory vaccine standpoint, as I will go into briefly with our COVID-19 program, it is fully funded at the phase IIb level with the U.S. government and BARDA, and then upon the results of phase IIb, should Sanofi opt in, this will also be fully funded phase III and beyond.
We have also worked in influenza, both from a seasonal influenza vaccine as well as a pandemic flu. What I will do now is highlight our interesting data from the COVID-19 study. As a reminder, this is a BARDA-funded study, phase IIb clinical trial. We have enrolled approximately 5,400 subjects. It was designed to compare safety and efficacy against a currently approved mRNA vaccine. The top-line safety data from the first 400 subjects in the Sentinel cohort are encouraging and actually very consistent with the safety profile that we have said all along and observed to date in many of our trials. We do expect the 12-month relative efficacy endpoint to read out in the first half of 2027, which is our main 5,000-subject cohort.
Now, there is not much in the news about COVID, but this is also a good reminder with this slide to share with everybody that there is still a high mortality with COVID. If you compare COVID to influenza, certainly a higher number. Also, the burden is with those who are age 65 and above, and so this is where we certainly believe that continuing to study COVID is not only important, there is a need, it remains a very deadly virus, but also it is a good indicator in terms of what we could be doing with other respiratory viruses to include flu. The current COVID-19 marketplace is concentrated amongst three companies.
If you have taken a COVID vaccine, you have most likely taken one from one of these companies, and when you sum everything up globally, it is still a $7 billion marketplace, and so for a small company like Vaxart, we would certainly love a piece of that pie. It is just a good reminder that although you are seeing, let us say, lower sales over the course of time, it is still a significant opportunity from both the U.S. sales standpoint and a global sales standpoint. Let us also remind ourselves that these are injectable vaccines. Ours, if it is in the marketplace, will be an oral vaccine. Would that change the mindset a bit? We certainly believe so, and this slide gets into that a bit more.
In our research, we have found that certainly recently, there are a lot of folks who will turn down receiving a COVID vaccine for a variety of reasons. It could be side effects, as you see in number one there. It could be just the convenience. I am busy, and do I really need to schedule an appointment to go to the pharmacy, stand in line, wait in line, wait for someone to give me that injection?
That could be another reason why someone may say, "Okay, maybe I am not interested in a COVID vaccine." We believe that opportunity on all of these is a reason why an oral pill vaccine opportunity still exists. Not only would we look at the share of those patients who have received one, because perhaps they are looking for something more convenient, or the ones who did not receive any at all, because there is a reason for them to now say, "Well, I can just stay at home, and someone could drop ship a vaccine to my doorstep." We believe this is still a great opportunity. I will now go into our phase II study design. As I mentioned earlier, this was approximately a 5,400-subject trial. It was divided up into two parts. The first part was the Sentinel safety cohort, which recently read out.
There were 400 subjects there. The main cohort, which has approximately 5,000 subjects, again, as a reminder, that will read out in the first half of 2027. We are all looking forward to that. The primary objectives were around safety and tolerability, immunogenicity, and finally, relative vaccine efficacy. The randomization, it also included age groups of 18 - 64, but also, just as a reminder, there were many subjects consistent with the U.S. population over 65 and high risk, having comorbidities. Here are the results from the Sentinel 400 safety cohort. First, as you will see in the orange, those would be the subjects who received our oral pill vaccine with a placebo injection. In order to blind the study, those subjects who received our oral pill would also have needed a placebo injection.
Then compared to the darker bar, which are those subjects that received placebo pill- non-Vaxart and the mRNA comparator. I think to no surprise to folks here in the audience, there is a lower percentage of injection site pain, even though you received a placebo injection, lower percentage of injection site tenderness, and a lower amount of swelling, et cetera. Even though folks receive a placebo injection, you are seeing that this compares favorably from a local immune reaction perspective. We are of course, very pleased and happy to see that. From a systemic immune reaction, we also compare favorably here. I certainly think about my family members and friends who received an mRNA COVID injection. Again, on the dark is those who received that, and you see a higher percentage of malaise, fatigue.
You see a higher percentage of headache for those receiving the mRNA, higher percentage in muscle pain, about the same on a loss of appetite. Again, from our standpoint, we are pleased to see that from systemic reactogenicity across the common events, ours was predominantly pretty mild. Again, I think the bars speak for itself, but again, a great outcome that we would want to see from a safety cohort. I will also review the case counts for COVID-19. As a reminder, this was not designed to be a statistical significant comparison between arms on efficacy. It was not powered to do that, but what you will see here is if you look at the case counts, you will see that it was essentially equivalent. The number of cases for COVID asymptomatic and symptomatic were similar in both arms.
From our standpoint at Vaxart, we are happy to see that there is comparable results from prevention of COVID and better safety in this population. As a summary, well-tolerated, no vaccine-related serious adverse events, no sustained Grade 3 or higher adverse events related to the vaccine were reported in either arm. You see that the mRNA competitor had greater systemic reactogenicity than our oral vaccine, and also the majority of those folks receiving the mRNA had higher injection site reactions. Very consistent, and certainly, we are looking forward to what the final results will be next year. In terms of norovirus, I will spend a few minutes just updating everybody here. Once again, Norovirus is responsible for up to $10 billion of annual U.S. economic burden. You think about if you have had Norovirus, how that will wipe a person out.
They may not be productive, they have to take care of their children, and they have to stay home. All these reasons where there is an opportunity, and this is a first-in-class potential. There are no approved norovirus vaccines that are in the marketplace right now, and so we certainly believe with our platform, there is an opportunity. We have a bivalent vaccine candidate that protects against the two most dominant strains, GI.1 and GII.4, and we think that this will also provide improved protection. We have been on a journey where we had a first-generation construct, and now we have a second-generation construct, which we are very excited about. Just as a marketplace reminder in terms of why norovirus, as I stated earlier, 22 million U.S. cases per year.
Also, on the bottom there, if you compare against other marketplaces where there are current approved vaccines, so shingles and RSV, there are vaccines already in the marketplace. If you compare the cases there, quite a few more norovirus cases. Hospitalizations, certainly more than shingles, about the same as RSV, and then deaths, a little higher than shingles, not as much as RSV. But it gives us, I think, the backdrop for us to believe in the fact that there is a market for norovirus, and there is a market for a norovirus vaccine that we are working on. Quickly, what I will cover is just a bit of our journey. From our original first-generation construct, we did a norovirus GI.1 challenge study. We showed a relative reduction in infection versus placebo, also a relative reduction in norovirus AGE, gastroenteritis symptoms.
This served as a backdrop for us where one, we know that from machine learning that the right antibodies, the right functional antibodies, the NBAA, is what we will identify as a clear correlate of protection for us as we move forward. We are using those correlates of protection to help guide us in terms of developing our second-generation candidate, which, as you see here, we have been able to move forward with our second-generation candidate. We have seen an increase, a significant improvement in the geometric fold, a rise in a norovirus-blocking antibody assay, NBAA is what we call it, and we have seen this for both GI.1 and GII.4 in our second-generation construct. Obviously, our GI.1 construct first generation did fine in the challenge study. This one with this data, we believe, would be also potentially successful in a phase II study.
And where we are at right now at Vaxart is we're waiting for either a partnership investment or a general investment to move this vaccine forward. This is also supported by eight completed clinical trials that we have in norovirus, which will help us inform designing the phase II study and beyond. I'll close with what we're doing from an influenza flu standpoint. Many years ago, we also did a phase II challenge study against the current marketed vaccine. We've shown that there is an opportunity for protection, both from mucosal and serum antibodies, reduced shedding. It is a favorable safety profile. Also from a pandemic standpoint, we also had started an H5N1 program, which showed a very strong survival benefit in animals. This is the summary of the head-to-head study that we conducted.
This was also funded by the U.S. government, by BARDA, and this was against the currently marketed vaccine, Fluzone. As you can see here, there was a better protection against Fluzone. This creates an opportunity in the future for us, should we move forward with a flu vaccine construct. From a pandemic flu standpoint, we also had designed a flu vaccine during the avian flu pandemic. We tested this in ferrets, and the simple takeaway here is those ferrets who received the flu construct survived at 100%, and those who received placebo did not. This again, gives us a good opportunity as we develop the flu program, which again, same thing, we're hoping for any type of a partnership or investment as we move things forward. Speaking of which, here are our upcoming milestones, and I'll also highlight our current collaboration agreement.
Our current collaboration agreement for COVID-19 is with Sanofi. As a reminder, we entered into this collaboration agreement with Dynavax, which was subsequently purchased by Sanofi. At this point, we have already received $30 million, an upfront payment of $25 million, $5 million equity investment. We have a potential of up to $670 million in milestone-based payments. Those are tiered royalties as well, anywhere from the low to mid-teens. This is always contingent upon Sanofi opting in after the phase IIb results are revealed. From a milestone standpoint, as you see here, we expect to complete the phase IIb in the first half of 2027. This will then allow Sanofi to potentially opt in. As you see, that could be a $50 million opt-in milestone, followed by additional regulatory milestones down the line.
We're working very closely with them, and we certainly have enjoyed our current collaboration with them now that they've purchased Dynavax. Next slide. I'll close with the fact that we have multiple value-creating milestones, and our cash runway is into the first half of 2027. COVID-19, as I shared, we are conducting this head-to-head study, and the readout would be in the first half of 2027. We have opportunities both with norovirus as well as influenza, and from a company standpoint, we're all focused on the execution of the COVID study to ensure that we get to that milestone, which is going to be very important for us. I'm also pleased that we have a very strong management team that supports all of this.
We have our Founder and Chief Scientific Officer, Sean Tucker, who has been with the company since day one, and all of the science is based on everything that he has worked on. Our Chief Medical Officer is James Cummings, who has worked in numerous vaccine companies. Our CFO is Jeroen Grasman, and then recently joining us as our Chief Technology Officer is Todd Lopeman. He actually came from Dynavax, so he had a chance to work with us while he was at Dynavax, and now has decided to join us for this cause. It is great because he has overseen the CMC and development of a lot of vaccines from its infancy to actually a commercial marketplace. Edward Berg is our GC, and Laurie Hastings is our Head of HR. With that, in closing, I think we have some great opportunities in front of us at Vaxart.
As I mentioned before, we have a differentiated platform. We are approaching an important data point. We have a partnership with a global vaccine leader, with Sanofi. The next catalyst is actually fully funded, so we are one of the only companies that continues to be funded by the U.S. government in a vaccine trial, and they will fund us all the way through. In fact, they have modified the last agreement to allow for further analysis of the study, and so we are pleased to see that in the last modification. Obviously, this is an important head-to-head design because it is our oral vaccine platform against a currently approved mRNA, and as mRNA continues to progress, we think we would compare favorably, certainly from a tolerability standpoint and hopefully from an efficacy standpoint.
We are also looking forward to working more on norovirus and flu, and we certainly have a great leadership team in place to take this company forward. I want to thank everybody for your interest and sitting in on this presentation today.