Developing Effective COVID-19 Oral 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 . 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 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 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 or T cells' response throughout the blood, but you can actually create it at the wet surfaces and that's the first site of 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.

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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 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 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. I think we are pretty much the farthest ahead when it comes to developing something that could be used for many, many different indications.

Karen Jagoda: This is pretty exciting work. So in the old days when they did have the oral vaccines, did somebody decide it was just more efficient to use the injection model instead of trying to handle the liquid? I recall, I'm going to age myself here, but getting the on a sugar cube. So I guess that's what we're talking about here, isn't it?

Sean Tucker: Yeah. I mean, let's go back a little bit in history. In the old days in the vaccine development, what they did to basically make a vaccine is they would either take the pathogen of interest, inactivate it completely or attenuate it, basically make it weakened so that it would be able to elicit immune responses without causing disease.

Sean Tucker: And what they had found is that the oral polio vaccine was actually quite effective, but there were some issues with that because that attenuation could potentially be reverted and actually lead to causing polio. So there was an impetus to basically build something else, and so they were able to create an inactivated polio vaccine that for the developed world seemed to be a better situation.

Sean Tucker: So what we did essentially is, we wanted to take advantage of the idea of oral delivery but not build something that was attenuated replicating and pathogen specific. So we had to create this technology that could be used for just anything and it took a little while to figure out.

Sean Tucker: And what we figured out is how to take essentially a dead polio virus and cut and paste what I would call the proteins of interest or the DNA that codes for the proteins of interest of each pathogen into that system and have it recognized, and so that's how we've improved upon the idea. Obviously people have made oral vaccines in the past, it's just that they were using the older technology, which had some limitation.

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Developing Effective COVID-19 Oral Vaccine in Tablet Form with Sean Tucker Vaxart An Empowered Patient Podcast Published December 21, 2020

Karen Jagoda: That's a great description. You were obviously working on other indications before COVID came along. So are you going to be able to go back to some of that work in the near term or is COVID really your main focus right now?

Sean Tucker: Well, COVID is going to be our main focus for the foreseeable future, but we did announce just a few a month ago or so that we are going to actually revive our Norovirus program. So we're going to be making an oral Norovirus vaccine, and we'll be proceeding into phase two trials sometime next year.

Sean Tucker: So from that standpoint, we do have other indications we are pursuing, but right now COVID is our main focus. I expect that Norovirus will also be revived next year and I would anticipate other things coming along as well.

Karen Jagoda: I always like to think of these stories as a silver lining or catalyst for business development and research development, something you didn't expect a year ago, so it sounds like you've really jumped on this. And the idea here is that patients like yourself would be more willing to take the pill as opposed to getting the needle. Is that the feedback you're getting from the people you are working with in your clinical trials?

Sean Tucker: So I think everybody appreciates that everyone would rather have a tablet to take that's an adult, rather than a shot. I mean, certainly nobody likes to go get stuck with the needle in the arm. Obviously there's a lot of reasons that make an oral vaccine attractive and that's one of it from the standpoint of the patient.

Sean Tucker: The subjects are more likely to take a tablet than they are a shot. And certainly from the standpoint of room temperature, stability, I mean, as you probably have read quite a bit about the Pfizer vaccine looks really good from the standpoint of efficacy but it needs to be kept at really, really low temperatures and most clinics don't have that. There's a big advantage from the standpoint of the Vaxart technology from this oral room temperature oral tablets that we don't have to deal with the same freezer issues.

Karen Jagoda: And also shipping issues. We're seeing all this with the dry ice on the airplanes and the special freezing facilities. So it sounds to me like your drugs would just be handled like any other drugs in the distribution channel, is that right?

Sean Tucker: The usual way that vaccines are handled is everything's kept refrigerated. So ours could even potentially have an advantage over the existing channels. We could use the existing vaccine channels from the standpoint of just refrigeration, but we don't need to, so I think that is a big advantage for us.

Karen Jagoda: Tell us a little bit about your background. You're obviously a curious scientist, so tell us how you got here.

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Developing Effective COVID-19 Oral Vaccine in Tablet Form with Sean Tucker Vaxart An Empowered Patient Podcast Published December 21, 2020

Sean Tucker: I started off as an engineer. I was a chemical engineer working at a normal chemical company and got interested in and learned a little bit more. I have a bachelor's in chemical engineering and then I got a master's in biochemical engineering.

Sean Tucker: And then as I was working in biotech I started getting very interested in the science and one of my colleagues told me, "Hey, you should really look into immunology. This is an exciting field that's growing, and there's lots of different things going on." And so I went back to school, got a PhD in immunology and have worked in biotech in the San Francisco Bay Area over the last 20 some odd years, so it's been quite an adventure to say the least.

Karen Jagoda: And who is on the team at Vaxart?

Sean Tucker: We have a lot of industry experts. The head of Vaxart is a guy named Andrei Floroiu who has got some background in terms of investment and other biotech companies. And we have some industry vets from places like MedImmune and Dynavax and Merck. So we have a lot of people on the team that have lots of experience in biotech as well as in vaccines.

Karen Jagoda: So when do you expect that the vaccine for COVID-19 might be available for general distribution?

Sean Tucker: That's always a good question. And then because of the way that the regulatory path is changing constantly, our plan right now is to do what we call an efficacy trial. It's going to be a phase two, and we believe it'll start sometime early next year.

Sean Tucker: And then once we get a readout of how well the vaccine does, for example, Pfizer reported about a 95% essentially efficacy rate, we will be able to hopefully get some similar data. Then we will make a proposal to the FDA and worldwide other regulatory agencies, what it takes to get licensure.

Sean Tucker: And so my expectation is that maybe in a year from that we will be having some conversations, but it's just as you're probably aware, because things are moving very rapidly in this field and the regulatory environment it's likely to change with the fact that Pfizer and are pretty far ahead, I can't give exact timelines for availability.

Karen Jagoda: But I think you're underscoring the need to have alternatives to those kinds of vaccines. And so is that really the justification for continuing on here, that those injectable vaccines aren't going to handle everybody's needs?

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Developing Effective COVID-19 Oral Vaccine in Tablet Form with Sean Tucker Vaxart An Empowered Patient Podcast Published December 21, 2020

Sean Tucker: I'd say that, look, it's very exciting, the fact that we have vaccines that have a really high efficacy. But the key thing from the standpoint of the world is to be able to get a substantial number of the people of the world vaccinated, such that there's herd immunity and the virus can't really transmit because that's really going to solve the problem. And it may be that the needle vaccines are only going to be able to solve a certain percentage of that problem.

Sean Tucker: We think that oral tablets have a different approach and are able to solve some of the things that vaccines can't do. And my expectation is that we're not going to be able to find a COVID vaccine that's going to be one take and you'll be done for life. It's likely that you're going to have to get repeated vaccination over time. And certainly, from my standpoint, I believe the oral tablet is certainly the best way to approach this for boosting immunity going forward.

Karen Jagoda: Thanks to my guest today. Sean Tucker, founder and chief scientific officer at Vaxart, Vaxart.com. I'm Karen Jagoda and you've been listening to the EmpoweredPatientPodcast.com show. Follow me on Twitter @KarenJagoda, like us on Facebook at Empowered Patient Radio. Thanks for listening and we'll see you next time.

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