Developing Effective COVID-19 Oral Vaccine in Tablet Form with Sean Tucker Vaxart An Empowered Patient Podcast Published December 21, 2020 Karen Jagoda: Welcome to the EmpoweredPatientPodcast.com show. I'm Karen Jagoda and my guest today is Sean Tucker. He's founder and Chief Scientific Officer at Vaxart, that's Vaxart.com and the topic is Innovations In Vaccines. So welcome to the show today, Sean. I appreciate you taking a few minutes to talk to us about this extremely timely topic. Sean Tucker: Thanks for having me. I'm really excited about talking about our platform. Karen Jagoda: So let's start with talking a little bit about the mission of Vaxart and why you decided to start the company. Sean Tucker: Sure. So the history behind the company is I could never go get a flu vaccine, because I just found it inconvenient to wait in line or call my doctor and get things scheduled. I just felt I was too busy, but I thought, hey, if someone could actually send me the vaccine that I could take every year I would take it all the time. Sean Tucker: So, what I came up with was the simplest solution from the user standpoint was basically just tablets because there's no device, no learning, and it's very easy to distribute. We spent the next several years trying to figure out how to make it simple for the user, but certainly make it work on the immunology side of things. Karen Jagoda: So the idea of an oral vaccine seems to be contrary. When we think of vaccines, we usually think about the poke in the arm. So is this a new technology that you've come up with? Sean Tucker: Yes. The short answer is, yeah. As you are partly aware, most vaccines are actually given by the injection in the arm and that's been reasonably successful in a number of cases. What we wanted to do was do something where you could swallow a tablet. Sean Tucker: The trick was basically coming up with a way for getting your immune system in the intestine to recognize that the protein was not just food, but something that it needed to mount immune response and then develop memory. And that was basically what we invented was a way to basically convince the immune system in the intestine to go after the foreign protein as a foreign invader and essentially create the memory so that it would work as a vaccine. Karen Jagoda: And to then send that throughout the body? Sean Tucker: Yeah. Again, the way your immune system works in the intestine, is that if you deliver your protein there and you can get it recognized as being foreign, you'll get antibodies and T cells basically throughout the body. Not just in the systemic system, basically the blood and the tissues, but also in the mucosal system Sean Tucker Vaxart Page 1 of 7 EmpoweredPatientPodcast.com ©TBI LLC 2020 Developing Effective COVID-19 Oral Vaccine in Tablet Form with Sean Tucker Vaxart An Empowered Patient Podcast Published December 21, 2020 where you're creating antibodies and T cells at wet surfaces and that's very difficult to do by an injection. So I think there was definitely a benefit from actually delivering your vaccine to some place like the intestine or the mouth. Karen Jagoda: This is really extraordinary information. So tell us about the general benefits of an oral vaccine. Sean Tucker: Well, I think that you can appreciate from the standpoint of the end user, that having a vaccine that can come to you rather than actually having to go get it is substantial. And particularly during a pandemic where most people are supposed to be cloistered away in their homes and not really being exposed to the outside as much as possible. Sean Tucker: But also on the standpoint of places that don't have refrigeration and a cold chain, it's really advantageous to be able to send out vaccine that's room- temperature stable, out to the little villages or rural areas of the US. So from that standpoint, it's phenomenal. Sean Tucker: And then of course what I just mentioned before is that if you actually give a vaccine at a wet surface, a mucosal surface is how we call it in the sciences, you can actually create not just an antibody or T cells' response throughout the blood, but you can actually create it at the wet surfaces and that's the first site of infection for a lot of pathogens. For example, like COVID where the first place that the virus invades is the nasal respiratory system or the intestinal mucosal system. Karen Jagoda: So is this form of a vaccine cheaper to produce as well? Sean Tucker: There are certainly cost advantages from the standpoint of manufacturing. On the upstream side of things, we do the same things that everybody else does in terms of growing cells in large tanks, essentially, and amplifying up the vaccine. What's more, I would say is how cost-effective on the downstream side of things it is. It's really expensive to go and put stuff sterilely into syringes and vials because you have to make sure that everything is sterile. There's a lot of testing involved and it's complicated machinery. Sean Tucker: When you actually use tablets, when you make your vaccine something in a dried powder and you put it in a tablet, that's actually pretty inexpensive. It can be done at very large volumes because one, it doesn't have to be sterile and the tableting machines can make tens of thousands of tablets every minute. It's really a phenomenally better system on the downstream side of things. Sean Tucker Vaxart Page 2 of 7 EmpoweredPatientPodcast.com ©TBI LLC 2020 Developing Effective COVID-19 Oral Vaccine in Tablet Form with Sean Tucker Vaxart An Empowered Patient Podcast Published December 21, 2020 Karen Jagoda: I also think about these vaccines for injections about the waste, about the numbers that will be contaminated or the numbers that won't be used in a particular place in time for them to still be used. So do the pills have a longer shelf life as well? Sean Tucker: We think that those pills will have a much longer shelf life. From the standpoint of what we've done in the past, we know that the pills will last in the fridge pretty much indefinitely, and it room temperature stable we know that for at least two years. Similar vaccines that we've made prior to COVID have lasted it at 25 degrees Celsius without a problem. Karen Jagoda: So tell us a little bit about the work that you're doing on your vaccine development for COVID-19. Sean Tucker: Sure. So we have developed a vaccine candidate that's in tablets that are about the size of a small Advil, they're about 220 milligrams. And what we're doing is right now we're in phase one trials where we're assessing whether the vaccines are safe. So far, it looks pretty good from the standpoint, there's no serious adverse events and it seems to be well tolerated. And what we're doing now is basically measuring the immune responses to COVID after giving people those tablets. Sean Tucker: It's open label, meaning we don't have it placebo controlled. And the advantage of doing that right now is the standpoint we don't have to wait to unblind it, we can actually look at the data as we go. And so far everything is looking good and similar to what we've seen in preclinical models in terms of the immune responses and how the platform has behaved with other indications, such as Norovirus and influenza. Karen Jagoda: So you're currently making available an oral vaccine for influenza? Sean Tucker: We are in clinical development for influenza. We did what's called a challenge study earlier this year or published earlier this year. Where we essentially gave our oral tablet and compared to a market-leading, injected vaccine that probably everyone has taken on your podcast. And waited three months then just gave everybody influenza and then just counted how many people got sick. Sean Tucker: And what we found is we did equivalently well to the injected vaccine in terms of protecting against illness. And in fact, it looked like we actually did better from the standpoint of protection against shedding, meaning that flu replication and coming out the nose. Sean Tucker: So from our standpoint, that looked like a pretty good success. We have put that program on hold to focus entirely on COVID this year, but it is possible we're going to bring that back up in the future. Sean Tucker Vaxart Page 3 of 7 EmpoweredPatientPodcast.com ©TBI LLC 2020 Developing Effective COVID-19 Oral Vaccine in Tablet Form with Sean Tucker Vaxart An Empowered Patient Podcast Published December 21, 2020 Karen Jagoda: Who's your competition for oral vaccines? Sean Tucker: At this point, there's not really any competition from the standpoint of an oral vaccine platform. There have been other oral vaccines that have been marketed, for example, that you might be aware there's an oral polio vaccine that came out years ago, and there was also an oral typhoid vaccine. Sean Tucker: But there's not really a platform technology, something that can be used for any different indication for oral.