Hello, welcome to Oppenheimer's 36th Annual Healthcare Conference. I am Cheng Li, one of the biotech analysts here at Oppenheimer, and it's a pleasure to welcome you to our next company, Vaxart. It's my honor to introduce Steven Lo, CEO, and James Cummings, CMO at Vaxart. We want to leave probably a few minutes for Q&A after the presentation, so if you have any questions you want to send, please use the chat function at the bottom of your screen, or you can email your question to me at cheng.li@opco.com, which is C-H-E-N-G dot L-I at O-P-C-O dot com. With that, I will turn it over to Steven. Thanks again for joining us.
Great. Thank you, Cheng, also thank you to the rest of the Oppenheimer team for the opportunity for Vaxart to present at this week's conference. We're delighted to be here. As a reminder, we will be making forward-looking statements during the presentation. Again, we're just excited to talk to you about Vaxart. For those of you who are not familiar with us, we are pioneering a transformative approach to oral pill vaccines. Our platform is designed to generate both systemic and mucosal immunity. These pills are thermostable. We think it will revolutionize how vaccines are distributed as well as administered.
We are very excited that at the end of last year, we announced a partnership with Dynavax that validates the promise of our platform, extends our cash runway, and more importantly, allows for the future opportunity for our, one of our lead assets, COVID-19. Speaking of our assets and our pipeline, we have multiple programs. One of them is a BARDA-funded COVID-19 vaccine, which we have been working on and moving forward, which Dr. Cummings will share with you shortly. We also have a norovirus vaccine opportunity, where we have conducted numerous studies, and we're excited to hopefully move that forward in the coming year. We also have some very robust data in influenza, and all of these comprise vaccines that are on our oral pill vaccine platform, which also we manufacture here in the United States.
With that, I'll turn it over to Dr. James F. Cummings, our Chief Medical Officer.
Thanks, Steve, thanks for the folks at OpCo for having us. Next slide. Here we go. Our oral pill vaccines, they're different than the injectable vaccines in a couple of ways. The injectable vaccines, by and large, present with a systemic immunity circulating within the body. Our vaccine provides not just the systemic immunity, but also a mucosal immunity, that's generally featured by dimeric IgA. What does that mean? That means we have the ability to stop the invading virus or organism before it gets into the body's cells, which is potentially an advantage. From a safety standpoint, there's no injection site reactions because we're a pill, and our safety profile to date has been about the same as placebo, which is encouraging.
From administration, you know, Steve mentioned, you know, there's an advantage to having a thermostable pill and that you don't necessarily have to schedule time with a medical professional. There's no red bag medical waste in terms of syringes, needles, gauze, et cetera. There's no logistics chain of the freezers and storage conditions that are required for many of the injectables today. Next slide. Just an overview of how our vaccine works. You ingest the pill with a glass of water, it goes into the distal portion of the ileum, the small intestine. What is the pill? What's in it? Well, there's a delivery vehicle, the vector, that's Ad5, along with the pathogen of interest's antigen, and then the molecular adjuvant. This is something that tells the body, "Hey, this isn't food.
I know it's in your stomach, I know it's in your intestine, but you should really take a closer look at this from an immunologic standpoint." That's what generates or helps generate the immune response. Next slide. When we look at what type of immune responses we're talking about, I've already mentioned the fact that injectables, by and large, present with an IgG systemic immune response. This is very much a lock-and-key type of response. It's very specific to that, the antigen of that strain and organism or virus of interest. Whereas with a systemic and mucosal immune response, we do present with the systemic response, but along with that, this mucosal response with dimeric IgA, has multiple sticky fingers, if you will, points of contact for that offending organism.
It allows for a strain, cross-strain potential protection, certainly immune reaction, moving forward. We think that mucosal IgA response is really one of the critical pieces of importance when you're dealing with an infection that comes through a mucosal surface, like the respiratory tree, like the gastrointestinal tract, and others. Next slide. This is just a brief glimpse of our clinical pipeline. We have a COVID-19 vaccine that is currently in phase II testing, supported by BARDA. We're looking forward to top-line data of a seminal cohort in the near future, then towards the end of the year, we're looking at top-line data from the larger 5,000-person cohort. We'll talk a little bit about that. We have a norovirus vaccine.
Our first-generation vaccine, Gen 1, went all the way through phase II in a challenge study, and we showed protection against infection and disease. For the bivalent or second-generation vaccine, and we've instituted this Gen 2 construct, if you will, across the portfolio for the following reasons. It's a little more stable, it's easier to produce, and it's more immunogenic. Your cost of the goods should go down, your immunogenicity or your vaccine response should go up. There's a lot of good news there. We've shown that in comparison in the Norovirus. I will state that the COVID vaccine and across the other members of our portfolio are all using the Gen 2 construct now.
We have an influenza vaccine, where we've done a monovalent H1 vaccine study back in 2017, published in Lancet ID, a great peer-reviewed journal, where we took a look at our vaccine compared to the number 1 flu vaccine at the time, which was Fluzone. What we showed was statistically similar, but numerically superior prevention of infection and decrease in infection compared to placebo. That was a very much a good news story. Since that time, as I mentioned, we transitioned to the Gen 2 constructs. We have a seasonal or trivalent vaccine against influenza, as well as a pandemic vaccine against influenza. I'll show you a little bit of data about that in just a second, some very exciting preclinical data.
Looking at the HPV vaccine, that's in preclinical development, and this is a therapeutic vaccine. The difference being there's a lot of great HPV vaccines out there to prevent infection, but once you're infected, you know, the horse is out of the barn. A therapeutic vaccine in the preclinical models actually melts tumors that are caused by this HPV infection. Next slide. Looking at our current studies and portfolio. For COVID-19, our friends at BARDA were able to fund a phase II-B clinical trial. It's enrolled 5,400 subjects. That's 400 in the sentinel safety group, and that's 5,000 in the larger cohort looking at efficacy.
This is actually taking a look at efficacy over a 12-month period of time, where folks are monitored for infection by weekly swabs, as well as symptomatic disease by diary cards and visits to the clinic. We are excited to look at what could be a very robust data set from this study. Again, this study uses our second-generation vaccine construct. It's double-blinded, and folks either got the approved mRNA COVID vaccine or our test candidate vaccine in a head-to-head comparative efficacy study. Next slide. This is just an idea of timelines. As I mentioned, we did a 12-month observation period for both groups. The first group's primary endpoint was safety, and we should have the safety 12-month data on those 400 subjects coming out soon.
The 12-month safety data on 5,000 subjects, 2,500 receiving the mRNA vaccine, 2,500 receiving our candidate vaccine, that should be coming out at the end of the year. Next slide. Taking a look at positive phase IIb data, right? You've seen the timelines for this, but, you know, we do have an agreement in place with Dynavax, and Steve will go into that a little later in the presentation. There is the generation of potentially a $50 million milestone out of the remaining $670 million in development and commercial milestones that are attributed with this. It's a tiered royalty type of event.
We also think that positive results that come out of this study, it validates the platform, we're looking at other portions of the portfolio I just mentioned as really being able to take off. Steve, do you want to make any other comments on this slide before we go forward? We'll get to that in just a little bit then. Next slide. In terms of the next on our hit parade, our Norovirus, I mentioned that Norovirus is part of our portfolio, we're into the second gen version of that. It's a $10 billion annual U.S. economic burden, that's not just our numbers. That numbers comes from some pretty high-powered biostatisticians that have published in, again, the peer-reviewed literature.
The potential to reduce rates of norovirus infection, illness, and shedding. We've seen this in our vaccines when we did our challenge study in the Gen 1 construct, where we not only showed protection from illness and infection, but we also showed a marked decrease in viral shedding. When you shed virus, that's how you transmit disease. We're very excited about this potential additional impact. Next slide. You know, lifetime, you'll have likely 8 episodes of norovirus if you're not lucky. It could be more because it's underreported from a biosurveillance standpoint. Worldwide, you see those infections versus the U.S., $20 million, and the economic burdens and costs. The death and hospitalizations in the U.S., there's about 10,000 hospitalizations, 900 deaths. I would say that those numbers, again, are likely underreported.
The majority of those deaths are in the older or more senior population. Next slide. In terms of our challenge study, we showed a 30% relative reduction in GI.1 and a 21% relative reduction in acute gastroenteritis. We were able to make a p-value of 0.003, and for the relative reduction in norovirus AGE, it was 0.149. Not the p-value we were hoping for, but again, a numeric trend in the right direction, given the smaller numbers of this study. We looked at virus in the stool, emesis incidents, and virus in the emesis for the secondary endpoints, as well as being able to identify what we feel are correlates of protection.
Functional antibodies, blocking antibodies, the NBAA that we've developed, as well as looking at fecal IgA, identify some correlates of protection using our machine learning concepts to push this forward. Really, the next steps for the correlates could be used with the second-generation to further vaccine development. Next slide. I mentioned that we had a second-gen construct that we've looked at, and this is the study. We did a lower and a higher dose of our second-generation construct compared to what is a higher dose one, E11 of the first-generation construct. Again, these were small numbers, right? We want to take a look at what the immunogenicity looked like when we gave these two different constructs, if you will, in these populations. Next slide.
When we take a look at it, we saw statistically significant improvement in neutralizing antibodies with our second-generation construct compared to our first-gen. 141% improvement in GI.1, 94% compared to GII.4, and GI.1 and GII.4 are the strains that are most commonly associated with infections in humans. Seeing this data really jump off the page at us, we're very excited to pivot over towards our Gen 2 construct for the next steps in our norovirus campaign. Next slide. Here we are in terms of the second-gen norovirus pathway or progress. We've already done the head-to-head, that's in the middle of the table, and now we're looking at a phase II-B study, which would be 600 subjects, and that's looking at safety and immunogenicity.
After which we would go to the FDA for an end-of-phase II meeting and confirm the design of our proposed phase III study. That phase III study, depending on feedback we get from the agency, could be anywhere from 10,000-25,000 subjects. We're very excited to move forward with that, should we have partnership or other funding to move that program forward? Next slide. Now on to influenza. As I mentioned, it's pretty exciting that we had demonstrated protective efficacy in influenza in the past. That was with the gen 1 construct. I think gen 2 will be even stronger. We have some interesting H5 pandemic flu data to share with you in the preclinical animal model, which is the ferret. Next slide.
Here we are looking at our protective efficacy or decrease in infection from our study that was published in Lancet ID, and taking a look at the difference between administering our candidate vaccine, Fluzone or placebo. Fluzone generated a 38% decrease in infection. We demonstrated a 49% decrease in infection with a p-value of 0.001. Statistically significant, and very exciting, I think, with the challenge strain of wild type influenza A H1N1. Next slide. I mentioned the very interesting ferret study. Ferrets are the model, the preclinical model we use in influenza vaccines and therapeutics. This was a great study in that for the ferrets that we gave our new construct influenza H5 vaccine to, they all survived. Anyone who received the placebo, they all died.
Looking at the middle ground, that was a previous construct. We're very excited to take a look at what our influenza vaccine can do within the human community. When you look at the amount of nasal viral load, I mentioned that we decrease viral shedding. Take a look at the impact on the right-hand side of the slide. The decrease in viral load for, you know, those who received our vaccine was greater than 2 logs reduced by day 3. Decreasing virus in the nose should decrease viral shedding, and that should decrease transmission of disease as well. Again, some pretty good news. Next slide.
Great.
I'll turn it back over to you, Steve.
Thanks, James. Just as James outlined, we have lots of important value-creating milestones into 2027. As he had mentioned, we had completed enrollment in our COVID-19 study back in late 2025. We expect to have the top-line data on the 400 subject sentinel cohort very shortly, and then by the end of the year, additional data for the 5,000 subjects. That's definitely important to us as we are tracking Norovirus as well. Our hope with either funding or a partnership is we can convince the phase II-B study, and from that standpoint as well, we're also looking at what we can be doing from the influenza standpoint. These are our important milestones certainly this year and into 2027. I'll end with just a highlight of our management team members.
You've met James here, but we also want to highlight our Founder and Chief Scientific Officer, Sean Tucker. Of all the sciences, is his vision, and we're also delighted to have on our team our CFO, Jeroen Grasman, our GC, Ed Berge, and our Head of Human Resources, Lori Hastings. We're a lean and mighty team, and, you know, we're excited as we get into some upcoming data. Just as a recap, as James has shared with you, our platform is unique, that it's designed to generate both systemic and mucosal immunity. He's talked about our thermostable oral pill platform.
We have our Dynavax partnership, which, as he mentioned, we have milestones at the end of phase II, and should Dynavax, or Sanofi, since Sanofi bought Dynavax, exercise that opt-in, we receive $50 million in a milestone payment, but also future milestones related to regulatory approval and the royalties. As, as you may imagine, we're highly focused on executing and finishing out our COVID study, and we again look forward to interacting with many of you. We wanna thank Oppenheimer for the opportunity to present and turn it back over to Cheng.
Great. Thank you, Steve and James, for the excellent and very comprehensive presentation. I think we have some minutes for Q&A. Again, I will encourage our audience to ask a question or send your question to me at cheng.li@opco.com. I have a few question I can just maybe kick things off with the discussion, and I think it's really impressive for the deal you made with Dynavax last year, especially in a pretty challenging, I would say, I mean, macro environment, also regulatory environment for infectious diseases. Can you talk about maybe to some due diligence that Dynavax did before reaching the deal and kind of the key point that they value for your oral COVID-19 program?
Great. Yeah, thanks for the question, Cheng. From our standpoint, we had, you know, quite a bit of interaction with Dynavax, and, you know, since we're based in South San Francisco, they're actually on the other side of the bay in Emeryville, so it was very easy to have lots of interactions. As any company would do during the due diligence, they're going to get into a lot of the things that we're working on, right? Validating the science, understanding the platform a bit more, what we have done with some of our regulatory submissions, the whole clinical trial design that James covered, what we've heard back from a data safety monitoring board, to also how we're manufacturing this oral pill vaccine, which again, is in South San Francisco, and finally, our intellectual property rights, right?
It was very extensive, and we were certainly happy when they decided to move forward and give us the $30 million, $25 million cash upfront, plus a $5 million equity investment in the company. You know, from there. You know, that was announced in November of last year, but of course, they've also had their news, and they have subsequently.
Yeah.
been acquired by Sanofi on December twenty-fourth.
Yeah, I mean, it's great to see, like, the continued M&A activity in the field, including the over $2 billion deal between Sanofi and Dynavax. I mean, just maybe following on that, any just, like, thinking about how to work with, like, a new partner, which is bigger and also is more, I would say, experienced in those kind of, both COVID and probably, like, influenza.
Yes. Yeah, by, in a sense, by default, our partner is not just Dynavax, but it's now Sanofi. I think anytime there's a large player involved, we're very happy because they are one of the market leaders, as it turns out, with vaccines, right?
Yeah.
They continue to make investments in vaccines. They believe in vaccines. They have great market share, from our view, we're happy to have that interaction with them. They are certainly aware of what we are working on. Certainly in their diligence with Dynavax, they, of course, looked at all the deals that Dynavax has. Obviously, it's no surprise to them that, you know, Dynavax is in a collaboration with Vaxart.
Got it. I think we are probably looking forward to the 4,400 sentinel cohort data. I think you mentioned that'll be coming shortly. How should we maybe frame the expectation? I think it's mostly on safety, but, I mean, any kind of potential sign on efficacy we are hoping to see, and how would you maybe help us frame, like, a base case scenario of the data from those 400 sentinel cohort?
As you know, as I mentioned, the primary endpoint of that cohort is safety, so we should have some high-level safety data. You know, another piece of it is looking at efficacy, looking at first case of symptomatic disease or first time of infection. These numbers are small, so there could be overlap of the error bars. It could be, you know, a home run. I'm not sure. I'm blinded just like everybody else. Once we, you know, uncap that data and take a look, we'll be presenting it, and I think that, it's gonna do a couple of things, right?
Validation of, you know, the platform of the construct is one thing, then not just making sure that it's safe, but taking a look at what, over a 12-month course of time, the impact of our vaccine against infection or symptomatic disease could be compared to, directly compared to an mRNA injectable that's been approved, right? I think that, you know, mRNAs were a good first, push in terms of against a pandemic. As we look forward, we're hoping for better, faster, stronger vaccine alternatives. I think that we fit that bill.
Yeah, definitely looking forward to that data. Also, I'm just wondering: how will the 400 sentinel cohort data inform you have, like, 5,000 patient data, I think, expected later this year? Yeah, how should we, like, inform the.
how would the 400 patient data inform the 5,000 patient?
Yeah, well, so as I said, the real purpose of that, the primary purpose of that, 400 person cohort was a sentinel safety cohort, and we've gotten through the observation period where the DSMB would say, "Stop," right? Now, I meet with the DSMB regularly across the study to ensure that we would continue, and that's I think that the larger impact would be, was there a safety signal? Well, we didn't see anything while we were executing the study that would encourage us to stop, so I would say that I don't expect that to happen coming up. That's my forward-leaning statement.
In terms of impact overall on the study beyond that, I think that it should give us a sneak peek at what the potential efficacy could look like. More than that, I, you know, I think we're gonna have to wait for the full study. Its impact on the full study, although it's nice to get a signal, I think we're gonna have to wait for the full amount of data. We'll see.
Yep, definitely looking forward to that. Maybe just moving to the norovirus program, I think, again, you kind of have a pretty impressive data with your second-generation construct, and you show really good, like, immunogenicity compared to the first-generation construct. I mean, just curious, I think you mentioned you are probably gonna look for a partnership to move the program to, like, a phase II-B and Phase III trial. Just any comments or color can share on the interest level from, like, partners and what is the really the best way to move the program forward? I mean, there's, like, a quite significant unmet need for norovirus.
Right. Yeah, what was interesting is we had, as a company, started a lot of conversations on a Norovirus partnership, and then we ended up finishing out a deal for COVID, right? Now it's time to get back to Norovirus, and with many companies, right, we have discussions not just about the one vaccine, but about the whole entire platform, right? It really depends on the company. You know, there is still interested parties. We're working through some of the questions that will come in, but also, in one of the slides, we even showed where a competitor, Moderna, is, right?
Yeah.
Moderna is in the process of finishing out their study, and I think it's safe to say that, a lot of the interested parties, they just wanna see what's happening with the competitor before they'll say, "Okay, let's move things forward." That makes a lot of sense. As a company, we also look at, you know, is this something that we want to continue to also invest, without a partner? You know, those are strategic discussions that as a company, we're evaluating right now. We believe in norovirus, as you mentioned, it's a great opportunity, it's an unmet need, and our commitment is still there.
Okay. Sounds good. I guess just lastly, I think you just mentioned you have a lot of things going on in your early-stage program, including the avian flu, and also you have some great data in influenza. Anything we should expect from your pipeline, this year, and also kind of the top priority for the company in 2026?
Well, certainly, as James mentioned, it's, the COVID study data results will be not only informative for COVID, but also the rest of the platform. That, I think, will also be helpful because we have more subject data that is now, you know, a full year. That, I think, is important. The deal with Dynavax actually has brought a little more attention to the fact that there is an oral pill vaccine platform.
that potentially could be paired with or other antigens. That's also another area that, I think we're having some early-stage discussions, but, you know, we always keep things with a lot of optionality because it's just important that we move the whole platform forward.
Got it. just any additional probably indication you think your platform can apply to, and besides, yeah, the key focus on norovirus, COVID, and also flu, any just additional, you know, areas we can potentially go?
From my standpoint, anything that comes through a mucosal surface to infect you, the impact of our mucosal immunity would have its greatest effect, right? Any pathogens that come through the respiratory tract, through the gastrointestinal tract, or through the genitourinary tract, I think are potentially prime targets for us to take a look at as we look to expand the portfolio based on the success of the studies we're seeing now.
Steve?
Yeah, I think that's a great opportunity, as James mentioned, right? We want to keep the platform available for other antigens. That's part of the fun scientific discussion that our founder, Sean Tucker, likes to have. You know, stay tuned for potential other opportunities in the future for us.
Got it. Maybe just squeeze in one last question. I mean, those like mRNA vaccines. I think the next step is to do, like, combo shots or, like, combining, like, COVID with, like, flu. How are you thinking about maybe the combination strategy with the oral program? I think that's also a pretty exciting, like, next step.
Yeah. I think I'll take that as twofold, right? One is, what's another pill? One pill instead of two. We've shown that we can manufacture one tablet with several strains or different things in it, if one wanted to be additive, this is a very modular vaccine approach, where adding a pill or two together, we've demonstrated both clinically and pre-clinically in certain areas, a non-interference. You could take a pill or two or three and show, you know, immunogenicity that could be, you know, not just preventative, but potentially life-saving. You know, if there were an injectable that were already available, you could certainly take a pill and an injection. Although, I think the trend for vaccines that I see is getting away from injections, if possible, for a variety of reasons.
Yeah, of course. I think we're just about out of time, so we can just wrap up things here. I want to thank James and Steve again for joining us, for the excellent presentation, and we look forward to your, like, upcoming updates from the second cohort.
Same here.
Thank you.
Thank you for your time.
Yeah, appreciate it.
Of course. Our pleasure.