Vaxart Inc (VXRT) 2020 Q4 法說會逐字稿

Greetings, and welcome to the Vaxart Fiscal Year 2020 Corporate Update Conference Call and Webinar.

(Operator Instructions)

As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Mr. David Holmes of LifeSci Advisors. Please go ahead, sir.

Thank you, Hector. Good afternoon, and welcome to the Vaxart Corporate Update Conference Call. With me today are Andrei Floroiu, Vaxart's Chief Executive Officer; and Sean Tucker, the company's Chief Scientific Officer. During the course of the conference call, we will be making forward-looking statements regarding the future events and the future performance of the company. These forward-looking statements may be accompanied by such words as should, believe, could, potential, will, expected, plan and other words and terms of similar meaning.

Examples of such statements include, but are not limited to, statements relating to our ability to develop and commercialize our product candidates and clinical results and trial data, our expectations with respect to the important advantages we believe our oral vaccine platform can offer over injectable alternatives, expectations regarding our ability to develop effective vaccines against new and emerging variant strains, the expected role of mucosal immunity in blocking transmission of COVID-19, and our expectations with respect to the effectiveness of our product candidates, including our potential role in mitigating the impact of COVID-19.

All of these statements are based on the beliefs and expectations of management as of today. These statements involve certain assumptions of risks and uncertainties and could cause actual results to differ materially. We assume no obligation to revise or update forward-looking statements, whether as a result of new information, future events or otherwise. Investors should read carefully the risks and uncertainties described within the safe harbor section of our website as well as the risk factors included in the company's most recent quarterly and annual filings with the U.S. Securities and Exchange Commission.

Following Vaxart's prepared remarks, there will be a question-and-answer session, and a replay will be posted on the Investors section of the company's website. At this time, I would like to turn the call over to Andrei Floroiu. Andrei, please go ahead.

Thank you, David. Good afternoon, everyone, and thank you for joining us. I'm excited to provide an update on our clinical programs and outline some of our priorities for the coming year. We started the year with a -- actually, rather, we started last year with a peer-reviewed publication in The Lancet ID, featuring results from a Phase II clinical trial of our pandemic flu vaccine, a trial that was sponsored by BARDA. In this flu challenge study, we showed that our oral tablet vaccine protected against flu as well as the leading injectable flu vaccine, Fluzone.

Importantly, our oral tablet flu vaccine induced -- produced much lower levels of serum-neutralizing antibodies than Fluzone, less than 1/10 as much, but was just as protective. This is a very important finding. In the context of COVID-19, serum-neutralizing antibodies are seen as a key metric for injectable COVID-19 vaccine. So it is very important to recognize that for our oral tablet vaccine, serum-neutralizing antibodies are not an appropriate proxy for efficacy.

The protection of our oral vaccine in the flu challenge study was driven in part by B cells that recognize HA of IgA class as opposed to HAI type for the injectable flu vaccine. These results provide important evidence that our vaccine is working through a different mechanism of action than injectable vaccine. In fact, our oral vaccine generated a broader adaptive immune response, including mucosal T cells, and local IgA to effectively protect from influenza.

Early last year, at the beginning of the COVID-19 pandemic, our team had the foresight to design a vaccine that incorporates both the spike, S; and nucleocapsid, N, viral protein. This approach was based on our expectation that coronavirus was likely to mutate and spun new S-muted variants. The N protein is more conserved, less prone to mutations. And also a great target for potent T cell responses.

This and recent studies suggest that targeting the N protein may use broader protection from the new variants of SARS-CoV-2. Therefore, we are very excited about moving towards Phase II with a COVID-19 vaccine candidate that could be transformational, an oral tablet that works through a very different mechanism and which could prove to be a very valuable globally against the fight against -- in the fight, rather, in the fight against coronavirus.

We believe our COVID-19 vaccine constructs have several important advantages. One, the triggering of mucosal immunity, the first-line of defense against airborne pathogens such as coronavirus; two, the (technical difficulty) tablet; and three, the simplicity and lower cost of distribution of a room temperature stable pill.

Recently, we have seen the emergence of new SARS-CoV-2 strain against which some of the leading injectable vaccines offer reduced protection. At the same time, it has become clear that mass vaccinations by needle take a long time.

And that new strains may emerge faster than we can vaccinate people. Therefore, a better solution is needed, given that COVID-19 may be a challenge for years to come. Our strategy for tackling this global challenge is to employ a multivalent portfolio approach, looking to improve on many aspects of the first generation injectable vaccines, including convenience and speed of administration, breadth and depth of protection and ease and cost of distribution.

This involves advancing our S and N vaccine candidate into Phase II, while in parallel developing S-only vaccine construct. We believe that with our COVID-19 vaccine portfolio, Vaxart will have multiple paths forward depending on geography. In the developed world, annual boosting of those previously vaccinated are effective with the potential of comparing cross-variant protection. In the developing world, de novo vaccinations were a much more practical solution than cold chain dependent injectables.

Based on the fundamental underpinnings of our overall delivery platform, we have also restarted our norovirus program. As a quick reminder, the United States has approximately 20 million norovirus cases every year. Health economic impact is felt mainly by children under the age of 5 as well as elderly, over the age 65.

Recently published health economic data from the American Journal of Preventive Medicine puts the cost of over $10 billion annually. Based on this data and internal estimates, we believe there is an annual $10 billion-plus opportunity for a norovirus vaccine in the U.S. alone. We are currently in the clinic with this norovirus vaccine, administering booster doses to a few patients who participated in our earlier norovirus Phase I bivalent study.

The data we'll generate here should give us an indication of the duration of protection provided by our vaccine as well as the magnitude of response that is generated by the booster. In addition, this year, we have 2 additional studies planned. The first will evaluate our norovirus vaccine in people over the age of 65. And the second will be a challenge study that will provide us with efficacy data in this disease model.

I'll conclude by reminding everyone that to date, we have dosed nearly 500 subjects with vaccines based on our oral platform, across 13 clinical trials targeting 7 different viruses.

And now to provide some additional scientific background, I would like to pass the microphone to Sean to discuss our COVID-19 oral tablet vaccine Phase I results. Sean?

Thanks, Andrei. As this was a Phase I study, the primary objective was to determine the safety of VXA-CoV2-1, our oral COVID-19 vaccine delivered by tablet. Overall, the vaccine was appeared to be well-tolerated. 60% of subjects reported no symptoms in the 7 days post vaccination. And among those 40% who did experience symptoms, the majority had only mild symptoms. These resolved without the need for medical treatment. No subjects discontinued this study do a solicited adverse event, and today, there have been no serious adverse events reported.

The secondary objective of the study was to determine immunogenicity of the vaccine. Overall, immune responses against SARS-CoV-2 were observed in approximately 85% of subjects. We are very encouraged by the substantial T cell responses we saw as a result of the tablet vaccine. And I'm delighted to say that these results are the best we have ever seen in a human study.

The cytotoxic T cell responses at day 8 had a high percentage of cells that made gamma interferon, TNF-alpha and CD107a in response to stimulation with the S protein, with substantial increases compared to the first day of the study. Potent T cell responses may offer protection against severe COVID-19 illness across multiple variants.

These cell plasma blasts, which are the immune cells involved in antibody production, also increased in subjects' post immunization. There was also up-regulation of the mucosal homing receptor and surface IgA on those B cells in a dose-dependent manner.

While no neutralizing antibodies responses were observed in the serum of subjects, preliminary analysis showed that the increases in IgA responses, the S protein receptor buying domain and/or the N protein could be found in the majority of subjects. IgA, as a reminder, is a class of antibody plays a crucial role in mucosal immunity, the first-line defense against respiratory pathogens.

These IgA antibody -- specific IgA antibodies were detected in several different compartments, including nasal and saliva samples. Given the dose-dependent manner in which the B cells of interest were activated, future studies of this candidate will focus on dose-ranging and boosting to increase the mucosal immune responses to SARS-CoV-2.

In 2019, we anticipate starting several studies, which were highlighted by Andrei before. For COVID-19, we are going to perform a Phase II study, Part A, immunogenicity and dose ranging; Part B, efficacy; and a boosting study previously vaccinated infect in subjects. For norovirus, we are currently in a Phase Ib trial for booster vaccinations at 12 months or longer post first dose and we are planning dose-ranging Phase I study in the elderly, 65 years of age and older as well as performing a norovirus challenge study.

We look forward to advancing multiple studies throughout the year and delivering both clinical data and publications to support a proprietary oral vaccine platform technology. We expect these data throughout the year to provide the medical community and investors with a great opportunity for this novel and groundbreaking approach.

With that, I will now ask the operator to open up for questions.

(Operator Instructions) Your first question comes from the line of Mayank Mamtani with B. Riley Securities.

And appreciate the update. So maybe just picking on the last topic that, Sean, you talked about around the study design. Can you give us a little more color on the number of patients, the time lines? And maybe also in context of the recent FDA guidance document that came out last week, how do you sort of accommodate for the focus there being on utilizing antibodies?

Hello. Sorry, can you hear me now? So yes, let's answer that. Yes, sorry. Yes, let me answer that question. So the first thought of that, of course, is the Part A is the dose-ranging study where there's going to be 3 different dose levels and priming and boosting at all 3 levels, the ends are 16, but there's also -- it's broken out into elderly and young people to sort of get a good mix.

And that guideline -- guidance will basically be able to provide us insights into how to go forward with an efficacy study and do -- and case the proper dose and dosing regimen into a Phase II efficacy study, which we plan to run outside the U.S. and placebo-controlled trial. And I believe the ends for that study were approximately a total of about 900. And obviously, with the recent guidance that has come out with the FDA in terms of using potentially surrogates, we have to reevaluate that.

And certainly, from this candidate, the VXA-CoV2-1, if it's a T cell approach, we wouldn't be able to use a surrogate from the standpoint of getting -- proving essentially efficacy, we would still have to do an efficacy study. And improve that the vaccine could prevent something such as severe illness and hospitalization.

And Mayank, this is Andrei. I just wanted to add to that, that our conversations with the regulators indicated that they are fully aware that our vaccine is a mucosal vaccine and they indicated flexibility in working with us to find the path to approval. So we don't expect the same kind of metrics and proxies that are being developed oriented to the vaccines to apply to us necessarily.

Actually, that brings me to the second question that I had around -- yes, your T cell response is comparably superior to what we have seen from others. And the recent Nature paper from [Sterling], and there's a lot of literature coming out highlighting the importance of IgA also. Maybe T cell comparison has sort of started to come out against other peers. But can you comment on how your IgA responses are looking like relative to other more like -- more of the intramuscular vaccine? Do you have any thoughts on that?

So just as a highlight, I would say that our IgA responses in terms of we've compared in different indications, head-to-head, our mucosal approach definitely produces much more mucosal IgA than intramuscular approach. I mean that's pretty clear. I mean -- and in this study, we have not, of course, done a head-to-head comparison between our approach versus an injected vaccine, but I would say that as far as I know, we're the first vaccine company to report getting mucosal IgA of significance. So as far as I know, that's where we're at.

Okay. And my final question was on norovirus, do you have any plans to do pediatric since that is also a big part of the population that gets exposed to it? And also what does that mean as a read-through because pediatric in COVID is also a very big need?

Yes. I think that right now that -- sorry, go ahead.

No, you take it, Sean.

So yes, we will be moving into the pediatric space on norovirus. I would expect this to happen in a number of years rather than this year. So I don't think it will really overlap. Well, we hope it won't overlap with COVID too much. The key thing for us is that while right now, all of our vaccines are delivered in tablets, which are really easy to swallow for someone who's 12 and older, it becomes -- it's not a format that will be allowed a small infant to basically take it up for a child.

And so we're developing other formulations to allow it to potentially be swallowed in a sort of a slurry with a buffer. So we are working on that but -- we will be moving into the pediatric space on norovirus.

Okay. Understood. And just last question then. Do you expect coronavirus vaccine to be a single boost or prime boost with a 1 month -- or you just don't know, you have to run the study, you're not sure yet?

Well, obviously, the answer is different with people that have been priorly infected or people that have been priorly immunized than it would be with people that are naive. We are doing this dose-ranging study, of course, with people that are naive, so we can understand more about the kinetics. But you might expect that for a lot of the western world countries, a lot of people will already be immunized within a year. And we will probably look at this in terms of a 1 dose sort of regimen on a boost.

And Mayank, just to elaborate a little bit on that. I think we -- what we want to do is to develop a portfolio approach that can accommodate different needs in different geographies and also keep pace with the evolution of the virus, right?

So whereas last year, the challenge was to develop any vaccine against 1 strain, I think the challenge is now becoming developing vaccines that can offer a broad protection against various variants that are present now, so let's future ones. So that's where we think that vaccines that target S and N, perhaps in combination with vaccines that only target S for various strains, may play a role.

(Operator Instructions) Your next question comes from the line of Vernon Bernardino with H.C. Wainwright.

Andrei and Sean, thanks for the additional details as far as the update on the programs with the COVID vaccine are concerned. So Mayank basically asked all my questions. But one thing that perhaps we haven't talked about in a while, I was wondering if you could provide update and that is, is there anything going on with your collaboration with Johnson & Johnson?

So that collaboration is still ongoing. And as you can appreciate, both us and J&J have been extremely focused and busy with our respective COVID-19 programs. And once there is something to announce as far as the next steps with our full programs, we'll make some public announcement.

Have you had any discussion with them as far as collaborating on the oral tablet COVID vaccine development?

Nothing of substance that we would have to -- would announce publicly for now.

Okay. And when, again, may we see results from the ongoing COVID vaccine trial?

So the only thing we said is that we are looking to start a Phase II trial in Q2. And as we get closer to that, we'll elaborate on time lines following that.

Your next question comes from the line of [Shubhendu San Roy] with Brookline.

So I'm Shubhendu on behalf of Kumar from Brookline. I really appreciate the business update. I had a couple of questions. One was, so for Q2, in terms of enrollment of patients for the COVID vaccine study, do you see any challenges, especially for older patients now that we have a few vaccines out there? Do you see that could be a problem or anything?

This is Andrei. Thank you for your question. Look, it's hard to predict the future, but we think that given the attractiveness of an oral COVID-19 vaccine, given the relatively small number of patients that we need for the dose-ranging study and given that we still expect a significant share of the U.S. population to not have been vaccinated. At this point, we don't see enrollment as being a significant issue. But we'll update as necessary as we progress.

And I would add that I think conducting a placebo-controlled trial in the U.S. and broadly speaking, developed world, may be a challenge because it's placebo controlled and they are large. But in the dose-ranging study, all of the subjects are going to be on active drugs so that minimizes the challenge.

Right. Right. And in terms of the product needed for Phase II, you think you would have enough supply for that?

Yes.

Okay. I had a couple of questions for the COVID results. And could you please comment on how long is the CD8 T response is expected to last? And you have a really good response -- CD8 T cell response, but then, do we have any idea of how long it is going to last?

Yes. This is Sean, by the way, of course. The -- yes, we expect the CD8 responses to last a long time. And the reason why we think so is because when people that have been infected with SARS-CoV -- the original SARS, you can find T cell responses 17 years later and cross reactive against SARS-CoV-2. So we do expect that most -- one of the advantages of a T cell response is that they are long-lasting.

We know that the magnitude of the responses we looked at prime are pretty high. And we know that the convalescent people from SARS-CoV-2 get about 0.2% -- we have interferon response. So our expectation is that our responses will stay and be maintained, and we'll be able to find those cells. And when we -- we'll have more guidance probably little later on that. But yes, our expectation is that T cells are going to be very long lasting.

Right. And so in the same breath, you expect the overall protection against illness and infection by the vaccines we expect long as well?

So yes. So I would say -- if you're talking about protection based on sort of a T cell response, we do expect it to be long-lasting. A T cell response is not going to -- by itself, will not provide sterilizing and protection but would protect against severe infection and hospitalizations. And that's what we expect to last for quite some time. And again, if we can boost the -- mucosal responses are really robust, we also potentially can actually block infection.

Your next question is a follow-up from Vernon Bernardino with H.C. Wainright.

Andrei and Sean, given the challenges perhaps conducting an optimal investigational COVID vaccine study in the United States as well as many countries in the western world where there has already been a rollout of the authorized vaccines, have you considered perhaps trying to do a study with the oral tablet vaccine just in Brazil, for example, because obviously, that is a variant of concern and one in which there has been very low vaccine efficacy demonstrated by the -- all the vaccines so far that have completed Phase III or in Phase III.

So Vernon, thank you for your question. I'll answer first, and then I'll let Sean add anything if he wants to. So from the get-go a month ago, we said that our intention was to conduct larger Phase II studies, placebo-controlled, looking for efficacy outside of the U.S. So that remains the plan. However, at this point, we -- as we said in the opening remarks, we see the world kind of divergence in terms of need. So in the developed world, there is a lot of interest for one, cross-variant protection, and then boosting, periodic boosting, whether it's annual or so on.

So one of the studies that we are looking to do in the developed world is to boost those that have been previously infected or vaccinated. And then to do de novo vaccinations as you suggested, in developing countries such as Brazil, India and so on. Sean, I don't know if you want to add anything?

Vernon, your question is spot on. Our intention is potential is to open up regulatory paths in Latin America, South Africa and potentially India to basically be able to address us, as you suggested, the strains that are emerging that are not necessarily covered by the vaccines very well. And again, with this product that drives a cross-reactive T cell response, that would be a pretty good way to find and look for efficacy.

Perfect. Yes. I just asked because it seems like it'd be the easiest study to do of all, especially if you're going to go to a boost strategy eventually anyway.

It's a very good question and strategy.

Your next question is a follow-up from Mayank Mamtani with B. Riley Securities.

Just on the topic of strategy, I thought I'll ask you this question. What about doing a challenge study? Have you guys opened any conversations with certain countries that have shown some willingness to at least be open-minded to it? And then my other higher-level question was, how do you sort of see the broader landscape of vaccines that are looking at either oral modality or going after [N 13]? Like what sort of you see broadly among your peers?

So let me take the first question. Sorry, Mayank -- sorry, could you please repeat the first question?

Just potential of doing a challenge study, like something similar to what you did in flu where you (inaudible) and the call...

I was thinking about your second question while forgetting the first one. So we've had concrete discussions in some regions where they are open to doing challenge studies but we feel like it's going to take some time for those to actually become reality. But of course, we'll be very interested in doing that in whatever region where they -- where regulators are open to doing that. And as far as your second question, I'll let Sean elaborate. We are not aware of any (inaudible) oral vaccines that are relatively advanced or in the clinic. So we don't think too much about that competitively. Sean, I don't know if you have anything else to add?

Yes. Just on the oral side of things, I'd say that we've for -- we've been in this business in the oral tablet for a long time, and there's definitely a lot of learning to do to get it to work, and we think our technology is very important for that. In terms of -- again, nothing has been reported. I think we're the first mucosal vaccine to report beta as far as I know.

And if competitors come out and report data, that's great. In terms of an end response as well. I mean, I think there's only a few other companies that are looking at N, and so far, they haven't reported beta. So I don't have -- I can't really comment on what they've shown yet.

Understood. And actually, a follow-up that I just got was on the publication cadence from Phase I data, like how are you thinking about that, Sean, just kind of putting this in a peer review journal? And also, I know you've considered working with universities like Stanford, where thinking about this as a heterologous kind of approach to a protein-based vaccine or an mRNA vaccine or even looking at studies where you can maybe in a prospective way, look at your data and compare it, be it T cell, be it IgA, to some of these other approaches in the more real-world setting. Like, when can we see some of that more sort of prospective and more direct comparison that we can see -- in a proper study, proper controlled study?

Yes. I mean again, I don't think we can provide guidance on timing for these things, but we certainly will write up results for the Phase I study. There is definitely some things that we'd like to finish and detail out before we actually go and write the manuscript. And you did mention something, yes, we do have lots of friends in the academic world, and there's ways for us to basically sort of look at our T cell responses in a sort of more, what I should say, head-to-head manner by collaborating with some of the sharing samples, for example, and everything else, some of those things will just take a while to get in place the agreements. But I do expect that we will get data coming out in Q2 without providing exact guidance at this point, but that would be a reasonable expectation is that we'll have a lot more to talk about in next quarter.

Ladies and gentlemen, we have reached the end of the question-and-answer session, and I would like to turn the call back to Mr. Andrei Floroiu, CEO, for closing remarks.

I want to thank everybody that attended this conference, and we're looking forward to progressing all of our programs and to updating you soon. Thank you so much.

This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.