Good afternoon, everyone. Thanks for coming for the last day of the Jefferies Healthcare Conference. Last but not least, we have Vaxart with us today. Together with me is CEO Mr. Steve Lo and also CMO James Cummings. All right, so Steve, I know you have a very unique platform, oral vaccine. Maybe we can start with some high-level introduction on your platform, and that'll be very helpful.
Sure, that's great. First of all, thanks, Leong, and we also want to just thank Jefferies for the opportunity to participate at this week's conference. I'll start with vaccines are in the news, right? Let's all admit that. From our standpoint at Vaxart, we're actually fine with that because I certainly believe that there's an opportunity for safer, more efficacious, and frankly, more convenient vaccines in this world. That's actually what Vaxart is working on. From our standpoint, think about the last time you may have gotten a vaccine. You had to schedule an appointment, whether it's at the pharmacy or with your healthcare provider. You had to wait in line. You had to check in. If you were taking an mRNA, you may even have to plan around the fact that possibly the next day you might experience some side effects.
Getting in line, waiting, and then the healthcare provider has to give you the vaccine. You compare and contrast that with what we're excited to be working on here at Vaxart is an oral vaccine. It's actually right here in one of these bottles here. Basically, the vaccine could be delivered to you, right? You could order it from the Amazon pharmacy, and it'll be dropped maybe by drone one day to your house. We're excited about the convenience and the opportunity there. More importantly, there's some good scientific reasons why we think our vaccines will excel. I'll turn it over to James to talk about that.
Thanks, Steve. I'm James Cummings, the Chief Medical Officer, and happy to be here. Our vaccine product is a pill, a tablet that you've just seen in that bottle. It is a non-replicating adenovirus vector that in it has placed the antigen, the area of interest for an immune response, as well as an adjuvant, a hairpin-turned RNA that is a TLR3 agonist that tells the body, the intestine in particular, hey, this isn't just a piece of food to eat. This is something immunologically you should pay attention to. The pill, taken with a glass of water, has its highest level of activity in the small intestine. It then activates the immune system to produce not just a systemic immune response, circulating IgG, for example, which is what the majority of injected vaccines produce, but we also produce a mucosal immune response, very specifically dimeric IgA.
Although an IgG systemic response may be more of a lock-and-key phenomenon that has to have an exact fit or close to exact fit to be effective, a dimeric IgA has the ability to have cross-reactivity when we see things like strain drift or strain change. We have shown that in some of our publications already. That, along with the thermostability of this pill, which goes out almost two years, as well as the durability of the immune response. In some of our studies, greater than 200 days of immune response measured after taking the pill, we think these things separate us from the injected vaccines.
Yeah, James brings up a good point just on even the health economic benefits of this, right? There is no cold chain storage, the logistics, again, not the use of a healthcare provider to provide the injection because it could potentially be self-administered. All that should also be accounted for in the overall healthcare cost and convenience.
No red-bag medical waste, right, which is another concern when you're looking at the overall healthcare cost.
Absolutely. I think that's definitely a very interesting and unique platform, oral vaccine, right? I think prime a lot of interest into your actual pipeline programs. I think recently been in the news, your COVID program that's under the BARDA funding. Why don't we start to talk a little bit about that?
Sure, happy to do that. First of all, back in history, approximately a year ago, we were awarded over $450 million under Project NextGen to study our oral vaccine versus an mRNA comparator. That was a word that came from the U.S. government. We actually also dosed 400 participants in a sentinel study with the XBB strain. We were getting ready to prepare for a 10,000-participant study with the KP.2 strain. In February, we had received a stop work order because the U.S. government, HHS, wanted to evaluate and just make sure that the money was appropriately being spent on this COVID-19 study. We're proud to say that we received a lift of the stop work order shortly thereafter, approximately 60 days after that. We have proceeded to move forward with the study. James will cover that shortly.
One of the things I want to once again point out is, number one, that stop work order was essentially for 90 days, and we received the okay to proceed prior to the 90 days. That is certainly a good sign. I think secondly, as we look out in the marketplace, we are only aware of being the only company that has had a stop work order lift. That also, I think, speaks to, again, the good working relationship. We want to thank the U.S. government and HHS and BARDA for allowing us to proceed. James can cover some of the logistics of the study.
Sure. As Steve mentioned, that 400-person sentinel group had already been dosed by the time that we had received the stop work order. The safety follow-up and a follow-up for immunology, that continued, right? The 400-person cohort continued on, but we did have to pause activities for the 10,000-person cohort. Once that stop work order was lifted, we went right back to activating study sites, taking a look at screening individuals, and then beginning to actually randomize and dose folks. On the 27th of May, we enrolled our first participant in that 10,000-person cohort. That cohort is very large. It is 5,000 people who will receive our candidate vaccine, the pill. It is 5,000 folks who will receive the approved injected mRNA vaccine comparator. It should take about six months or so to enroll everyone in this study.
The follow-up period is 12 months from time of immunization. During that period, we'll be doing a couple of things. We'll be collecting safety data. That's very important, safety first. We'll also be taking a look at immunologically what's going on with folks. What's the durability of their immune response, as well as is there cross-reactivity in that immune response? We'll be taking a look at efficacy as well. We'll take a look at efficacy really in two ways. One, from a symptomatic standpoint, if someone has the symptoms of COVID or has a concern, they'll come right back to the clinic. We'll take a look at them, and we'll be able to determine if they have COVID infection or not. If they do, we'll be taking a look at what particular variant of COVID they might have, the SARS-CoV-2 virus.
Also, every week, folks who participate in this study will be swabbing themselves at home and sending that in. So we'll be taking a look at surveillance for asymptomatic infection as well. I think that this, over a 12-month period, will give us a very good snapshot of the efficacy, not just of the strain of interest, but perhaps other strains that crop up over a 12-month continuum of follow-up.
Yeah, that's a nice, very nice overview. I think definitely this is a large-scale study funded by the government, and it equals 10,000 for the second cohort that you just started dosing the first patient in May, which is very good. I think you also gave us some overview on the study design. You'll track both the symptomatic and the asymptomatic infections. I think you mentioned about seven months for the enrollment.
About six months.
Six months.
That's projected. We're enrolling now, and we're learning as we go, right? Although we project out about six months, we're learning from that sentinel cohort of 400 people. We're also, as we continue down the journey of enrolling folks in this study, making some accommodation or adjustments to maximize performance.
Yep. It also tracks for the, well, it's easier to reach and equals 255 infections or you follow those patients to 12 months.
Correct. We'll follow everyone for 12 months if they'll have us, regardless. I think looking at asymptomatic infections as well will be very instructive.
Yep. I also just want to remind folks that the first sentinel cohort of 400 patients, the DSMB had some interim analysis, recommended to proceed without any change.
That's correct. After a few weeks to months of follow-up, our data safety monitoring board met. They're independent and concluded that we should move forward with the 10,000-person cohort and to make no modifications to the study design or the clinical protocol. We also had put that through with the FDA as well. Now we're embarked on that 10,000-person cohort study. That's a double-blind study. Every participant will get a vaccine and a placebo. Whether the placebo is an injection or a pill, everyone will get both a pill and an injection in this study. We won't know what they got until we unblind. They won't know what they had. We do have people involved in the study for safety's sake that will know and be able to unblind if there's a reason.
I think at the end of 12 months, we're very excited about the data that we'll have to offer.
Yeah, we've been very happy with the enrollment progress. One of the reasons could very well be that we're aware that we're really the only study that's going on. So we're not competing with other companies right now to enroll patients into this type of study.
You have an active arm of that approved mRNA.
Yes.
Maybe we can talk a little bit about, I know we kind of touched on that in your platform overview. How's your technology addressing the emerging variants?
From our standpoint, it's really a two or three-pronged approach across our platform, not just for our COVID vaccines, but for the other vaccines in our portfolio, be it influenza or norovirus or COVID-19 or others. What we look at is safety first, right? We have a very clean safety profile. It's very similar to placebo across our studies to date, right? Along with that, I mentioned our mucosal immune response and this dimeric IgA. What we found in our studies has been that not only do we have good immunologic capture, if you will, of the strain that this vaccine was designed to go after, but there's cross-reactivity against several variants of the strain and even other beta coronaviruses. This is a very compelling, I think, way forward in terms of looking at strain drift, the potential of strain drift.
When I mentioned that we'll be taking a look at folks who have either symptomatic infection or asymptomatic infection, we'll also be sequencing those isolates to see, well, what strains broke through, if you will. I think very exciting data points. Lastly, from a mucosal immunity standpoint, one of the benefits of our approach, and it's been demonstrated clinically, is we have an impact on viral shedding. Even if you were to become infected, we have an impact on decreasing the amount of shedding. We've shown it in norovirus with an over 80% decrease area under the curve of viral shedding. We've shown it in influenza, where in our previous H1N1 study, where we had a comparator to Fluzone, we actually showed a decrease in viral shedding. We'd like to show clinically, potentially, that impact.
We have done transmission studies in our preclinical models, and we have had an impact on transmission as well.
Yep, certainly. You have the cross-reactivity against different strains, but you also work on the mucosal that prevented the virus shedding, which is very critical for preventing the pandemic. Yeah. Maybe quickly, since it is a large study funded by the government, I know you received BARDA funding. Quickly remind us on the economics of the side for the funds. You have, I think, up to $460 million?
Yes. Throughout the process, we modify the agreement. Now the current agreement has us at $460 million. It's based on milestones. We have $240 million immediately available to us. That allows us to proceed with the study, as well as just as a reminder to everybody that as part of this agreement, we have what we would call a slight profit in terms of running the study, but also as a company, we earn a fee. That covers, of course, the personnel that are solely dedicated to this, as well as the outside costs, which would include vendors and CROs, et cetera.
Yep. And if I remember it correctly, right now you have up to $240 million already available for payment.
Right, right. It is all milestone-driven. As we proceed, we receive invoices from vendors or the work that we do, and then we bill the government. Frankly, we have been really happy with the turnaround time on the payment of invoices. That is important from a cash flow perspective.
Yep, that's great to know. Before we conclude on the COVID program, maybe any comments, lots happening on a macro recently. Any comments on your COVID program from your standpoint? How do you think you are being any potential impacts? Yeah.
Sure. As a company, we always want to be flexible and adaptable. This is a phase 2b study. Based on how it is designed, we were certainly pleased when the government did not change any aspect in the study. The amount remained the same. The number of participants remained the same. Essentially, there were no changes. From that standpoint, we are certainly very happy. In terms of what could happen in the future, whether it is a phase III, et cetera, I think we continue to be flexible and adaptable. I see that in the macro environment, there are discussions around if it is placebo-controlled. I think we are biased, but I think if we had our vaccine against placebo-controlled, I have a feeling we would do quite fine there. That is certainly an important piece. There is also some discussion around high-risk groups.
As James may have mentioned, we already have in the clinical trial design high-risk groups in the current study. We will certainly have some data related to that.
All right. Maybe let's shift gears to your norovirus program. Maybe you can give us a very high-level introduction on the norovirus, and not necessarily everybody know about it.
Sure. So norovirus is responsible for one in five cases of infectious diarrhea, right?
Yep.
Norovirus generally is seasonal. Winter vomiting disease in some areas of Europe would be its reference. What we've seen is that norovirus has a large impact on both the younger community, children up to age five or eight, and then the more mature community above 60-65 or so on up. The financial impact in the U.S. alone is said to be $10 billion annually. That's just in the United States. I think a lot of people when they hear norovirus say, "Oh, it's a cruise ship virus." Certainly it has impacts on the tourist industry and the travel industry, but it also has impacts in stepwise living communities for our older population and nursery school and daycare for those of you who have kids or have associates who may have kids.
I think there's a broad swath of society that could benefit from having a vaccine, which there is no approved vaccine currently for norovirus. Our take on this is we're looking to develop the vaccine first in the adult population. That would be more towards either those who are at higher risk or those in the elderly communities. We also have a pediatric program that would be to follow.
Yep. Yeah. No, norovirus, we've definitely seen that every now and then in the news flow. We'll certainly touch on that, that you do have another competitor who is doing that, which speaks of the market potential. I think norovirus probably will be your most imminent update from the company side. You will have around mid-year your data update on your phase I, which is a second generation of your new construct. Maybe let's talk a little bit about your second generation construct. How is that different from the first generation?
Sure. Our constructs for norovirus go after GI.1 and GII.4, the two predominant strains that impact humans for infectious noroviral infection. When we look at the difference between the first generation and second generation, we're always trying to improve. What we found across our platform was by making some tweaks in the design of the vaccine, we were able to improve immunogenicity on a very immunogenic vaccine to begin with. We were also able to make some tweaks that assisted with manufacturing. By making manufacturing a bit easier and more productive, one could depress the cost of goods.
Now with the data we've learned from our phase one and two studies with our gen one construct, we're going head to head in the clinic with our gen two construct as well at a low and a high dose of gen two versus what was our standing dose for the gen one construct. As you mentioned, we'll have that data mid-year. We're very excited about that.
Yep, because the enrollment has been completed and you do have head to head to your first generation construct, but with two different doses of your second generation compared to one is lower, one is higher than your first generation.
We're committed to going forward with the best possible construct, but also at the right dose. Again, when we look at the safety features of our vaccine in terms of the profile being very clean, we think that administration will be not just simple, a pill in a glass of water, but innocuous. It shouldn't make you feel bad, right? I think that's another important factor for getting a vaccine program that's accepted when there's really no vaccine yet on the market.
Yep. So maybe on the data update, so how much data should we expect and what venue will we do the announcement?
A couple of things. One, in terms of the data to expect, we'll certainly have the safety data. These are small numbers, right? We will look at trends. We think that we will trend better in immunogenicity with this new construct. We're looking at two particular immuno readouts. We've learned a lot from our previous studies. We did complete a norovirus challenge. Some of the dialogue we've had with the FDA in terms of looking at correlates of immunity, et cetera, will come into play when we're analyzing that data. We look at mid-year, but we hope to be back at Jefferies when you're in the U.K. to discuss even more compelling data.
We're happy to host you there.
Thank you.
Yeah, definitely you have some key learnings about immunogenicity correlates from your first-generation study. I think that's mucosal related.
It is. It's two things. It's the mucosal or fecal IgAs, so that dimeric IgA antibody that I mentioned. It is also a functional antibody analysis where we look at the impact of the antibody on the virus or pseudovirus itself in an assay that we have very well characterized.
Just quickly remind us, what did you see in the preclinical comparing these two constructs? Like how much more potent?
Substantially. More than tenfold, close to a hundredfold, somewhere in that range of improved immunogenicity. We expect animals do not always directly correlate with humans, which is why we do clinical studies. Certainly the signal was so positive that in speaking to our scientific advisors and our other key opinion leaders in the community, we wanted to ensure that we are going forward with the best possible design.
That's probably why you also have even a lower dose than your first generation.
That's exactly it.
Yep. Cool. Maybe still stick to the mid-year readout. How should we think about your definition of the success there? How is that going to impact your decision to the next steps?
We'll look at those two readouts. Specifically, the functional antibody is what I find most compelling, right? Then taking a look at those two particular readouts that we found to correlate with protection with administration of our vaccine. I think the next step really is after a dose and construct selection, moving forward with partnering support or additional funding to looking at a phase 2b. With the proper partnering or funding, we can move into a phase 2b study in the second- half of this year. That would position us nicely for an end of phase II meeting with the FDA as early as 2026 and the beginning of a phase III study shortly thereafter. I think a lot of things have to be coming down the pike in the next few months.
Very exciting. I think coming back to the norovirus overall market, there is another big player who is doing some efforts there. How should we think about their approach versus yours?
It is a very similar, I would say, comparison that we are doing in COVID, right? There is an mRNA comparator and there is us. We are also aware of another company that unfortunately did not have great results in norovirus. We know that it is certainly difficult. From our standpoint, we have no problem being the fast follower as James was outlining because whenever a new company goes into an unmet need, they have to sort of set up the market, talk about the need, and get patients to receive the vaccine. I think certainly if it is a traditional mRNA injection, as we talked about earlier, I think there is room for an oral vaccine, frankly. Again, I think from a convenience standpoint.
Again, not that we're always focused on, let's say, travelers, but think about if someone were to go on a trip, take a cruise, not only do you have to worry about getting into the clinic to get an injection before you take a cruise, wouldn't it be better if it were just essentially mail-ordered pharmacy to you right before your trip?
Yep. I guess we're just not sure if people want to take an injection for norovirus before you get on a cruise or whatever.
Certainly, I think that when we look at needle phobia or concerns about injections, that's a significant portion of the population. Again, with a pill-based format, taking a pill in a glass of water, I think has a more widely accepted rate.
Yep. I think another interesting point is that now you are doing the, well, it's different vaccine, but now you're doing the head-to-head comparison with COVID. That should give us some reason when thinking about the two different technologies.
I think when we look at both not just initial protective efficacy, but cross-reactivity, as well as duration of response, and then finally the impact we have on viral shedding. It should, those three things, and then layering convenience of taking the vaccine, those four things, I think really will come to win the day.
Yep. I think that all speaks to the uniqueness of technology and the value proposition there. I know you as a platform company have multiple pipelines ongoing. I saw some recent news from the avian flu. Why don't we talk a little bit about that?
Sure. Again, we've only given out a little bit of that data so far. More to follow. We do have an H5N1 or pandemic flu program as well as a seasonal influenza program at Vaxart. Our seasonal influenza program, we published some of those results in Lancet ID in 2018, where we went head to head with the then leader in injectable vaccines. We showed numerically superior, statistically same or similar protective efficacy against infection. We also showed a decrease in viral shedding in that same study. Now we have, in the preclinical models, we've looked at H5N1, the current pandemic strains of concern that are in the news probably all the time. We've used, in preclinical, the sort of gold standard is the ferret model for a challenge study.
In this challenge study, what I can tell you is that all of the animals in the study that received our vaccine, they survived. All of the animals.
You have a 100%.
100% survival compared to the comparator group, which received no immunizations. They all died. 100% fatal challenge resulted in 100% protection if they received our vaccine. Based on that, we're very excited about our influenza program and our pandemic response for H5N1 should that need and interest arise.
Yep. We will probably see your publication on the detailed data sometime later.
Yep. That's, again, more data to come, perhaps to your next conference, but also in the peer-reviewed literature. We'll be presenting that at some national and international meetings, as well as publicizing that in the peer-reviewed literature.
Yep. Cool. I guess maybe moving back to your norovirus program, I think any active conversations are ongoing. I'm sure there should be lots of interest in your technology. I know your phase two is pending on potential partnership and funding. How should we think about that?
Yeah, we've been really pleased with the number of conversations as well as, frankly, all the different types of companies who have expressed interest. Like us, we all want to wait until the phase one data and hopefully if positive, right? I have a feeling that many of these conversations will accelerate. We've been speaking to large multinational companies who already have, let's say, vaccines in their portfolio, and norovirus would fit in quite well. We've also been in touch with some regional players who are also in the vaccine space. This would be, I think, a nice complement to what they have. On top of that, this is not just solely dedicated to the United States. We're also seeing interest from companies outside the United States who are interested in licensing our technology as well as this program for their territory.
All of this has been very promising. That is why we certainly can't wait until mid-year where we'll see the results.
Certainly stay tuned on your mid-year data update. Maybe finally, regarding your runway, remind us what's covered under your current runway outside of the BARDA COVID program.
Sure. Our runway does have us into the first quarter of next year. Again, all of the COVID vaccine trial study dollars are committed from the U.S. government and BARDA. That is essentially fully funded. We, of course, have to hit all the different milestones. We did not currently budget for the phase two in the current budget. Our runway takes us to first quarter. The desire, of course, is upon positive results, hopefully, of the norovirus study, we will either have a partner help fund that, or at the same time, we may decide, because we want to keep optionality, we may decide to fund that ourselves and we will look at ways to do that.
That's very helpful. All right, gentlemen, thanks for attending the conference. It's always a pleasure to host here.
It's been awesome. Thank you very much.
Thank you very much. Appreciate it.