Vaxart, Inc. (VXRT) Earnings Call Transcript & Summary

Greetings, and welcome to the Vaxart COVID-19 Phase II Top Line Results Conference Call. A question-and-answer session will follow management's opening remarks. As a reminder, this conference is being recorded. I would now like to turn the webcast over to your host, Edward Berg, Senior Vice President and General Counsel. Please go ahead, sir.

Good morning, and welcome to today's call. Joining us from Vaxart are Andrei Floroiu, Chief Executive Officer; Dr. Sean Tucker, Founder and Chief Scientific Officer; and Dr. James Cummings, Chief Medical Officer. Before we get started, I would like to remind everyone that during the conference call, Vaxart may make forward-looking statements, including statements about the company's financial results, financial guidance, its future business strategies and operations and its product development and regulatory process, including statements about its ongoing or planned clinical trials. Actual results could differ materially from those discussed in these forward-looking statements due to a number of important factors, including uncertainty inherent in the clinical development and regulatory process, the extent and duration of the impact of the COVID-19 pandemic and other risks described in the Risk Factors section of Vaxart's most recently filed annual report on Form 10-K and other periodic reports filed with the SEC. Vaxart undertakes no obligation to update any forward-looking statements after the date of this call. I'll now turn the call over to Andrei Floroiu. Andrei?

Thank you, Ed, and thank you all for joining us today. We are very excited to talk to you about our Phase II COVID-19 data because we believe that what the world reads -- what the world really needs today is breakthrough innovation in vaccines. The world needs next-generation vaccines. Incremental improvements to what we already have are not enough to significantly move the needle. What we really need are novel vaccines that have transformational potential. We need vaccines that are easier to administer, that can enable more people to be vaccinated faster. We need vaccines that employ novel mechanisms of action to better harness the power of our immune systems, and we need vaccines that have more benign tolerability profile. So in this context, we are very proud that Vaxart is the first company to report data from the first part of our Phase II study for an oral pill COVID-19 vaccine that activates not only systemic immunity but mucosal immunity also. We believe that this positive data adds significantly to the evidence supporting the potential that Vaxart's oral pill vaccine platform has been transforming how we fight infections -- infectious diseases globally. My colleagues, Dr. James Cummings and Dr. Sean Tucker, will go over the study and our data in more detail. So without further ado, I would like to hand this over to Dr. Cummings. James?

Thanks, Andrei. As discussed in the press release we issued a little earlier this morning, we're reporting top line data from our Part 1 of our Phase II clinical study evaluating our S-Only COVID-19 vaccine candidate. I'll refer to this as the 201 study. The vaccine candidate evaluated in 201 study was developed based on the viral spike protein from the original Wuhan strain of SARS-CoV-2 that was prevalent really at the start of the pandemic, about 2.5 years ago [Audio Gap] not received prior mRNA COVID-19 vaccination, ages 18 to 55 years and 56 to 75 years. Subjects were randomized into 6 cohorts, stratified by age, vaccination history and dose. These subjects received either a high or a low dose of the S-Only vaccine on day 1 and again on day 29, and the immune responses were assessed prior to vaccine administration on days 1 and 29 and on day 57. The primary end point of this study was safety of the S-Only vaccine construct. And the data clearly shows that this candidate was safe and well tolerated. There were no vaccine-related solicited Grade 3 adverse events, which are events that subjects were specifically asked to report and include symptoms such as fever and fatigue and vomiting and there were no vaccine-related serious adverse events. These safety findings are consistent with the results from over 650 subjects who participated in clinical studies of our tablet vaccine platform. Importantly, few or no subjects in this 201 study reported any symptoms to the severity that were commonly reported in clinical studies of the mRNA vaccines. We believe that this differentiated safety profile, if we continue to see it in larger studies, could help many people who are reluctant to take an injected vaccine due to concerns over feeling ill or really needing to take time off from work or activities of daily living if they experience post-vaccine symptoms. This will help them overcome their vaccine hesitancy. And increasing the number of the total of vaccinated individuals is critical for controlling the spread of COVID-19 and getting the pandemic well in hand. The secondary end point of the 201 study was the immunogenicity of the S-Only vaccine construct. We're pleased that multiple assessments clearly demonstrate this candidate induces potent antibody and T-cell responses and stimulates both serum and mucosal immunity. As many of you may know, we previously conducted a Phase I clinical study of our vaccine candidate that was based on both the S and the N protein of SARS-CoV-2, which I'll refer to as the 101 study. Based on the results of the Phase I study as well as our ongoing preclinical research, we modified the vaccine construct used in the 201 study to the S-Only with a specific old increasing serum antibody responses. We believe that the data reported today demonstrates this modification really had the desired effect. We observed increases in serum antibody responses in the 201 study and generated a neutralizing antibody response profile that's similar to those reported when boosting mRNA vaccines, although the comparison is not from a head-to-head trial, so we interpret it with that limitation in mind. The geometric mean titer or GMT of our SARS-CoV-2 specific serum-neutralizing antibodies increased from day 1 to day 57 and ranged by cohort between 1.2 and 2-fold with higher increases seen for higher doses. Although we've not done head-to-head studies comparing our vaccine candidate with approved mRNA vaccines, our review of the published data for an approved mRNA booster indicates that the GMT rise was between 1.5 and 1.9-fold. For our study, the 201 study, among 18- to 25-year-old subjects previously vaccinated with mRNA vaccines, the GMT of SARS-CoV-2-specific serum-neutralizing antibodies increased 1.6-fold from 41 AUs per ml at day 1 to 778 AUs per ml at day 57. Notably, subjects who started with a lower titer were likely to have a higher increase. Our S-Only vaccine candidate achieved this neutralizing antibody profile while also inducing mucosal immune responses, which have not been reported for injectable vaccines. We believe this is a key differentiating factor between our oral tablet vaccines and injected vaccines. The 201 data demonstrate that approximately 50% of subjects who previously received an mRNA vaccine had at least a 1.5-fold increase in mucosal IgA antibodies after receiving the S-Only candidate. Additionally, all subjects who had a mucosal response to the S-Only vaccine and again, I want to remind everyone out there, it's based on the Wuhan strain. We showed that this mucosal immune response also had cross-reactivity with the Omicron variants, including BA.4 and BA.5 as well as other coronaviruses. Again, these cross-reactive responses were observed in subjects who had previously received an mRNA vaccine as well as in naive subjects that is those who really had not previously been vaccinated against COVID-19. We believe a key benefit of our mucosal immunity platform is the ability to generate robust, diverse immune responses that may be able to address these emerging viral variants and may help the global community to get out from behind the immunologic curve or protection, where, unfortunately, we've been for the past 2 years as the emergence of new viral variants outpaces the ability to update the currently approved injectable vaccines. Another finding of the 201 study is that the S-Only candidate boosted the immune response in subjects who had previously received an mRNA vaccine series. We believe these data demonstrate that our oral tablet vaccine candidate may be able to provide an additional benefit to the millions of people worldwide who've already received an mRNA vaccine. It's clear that additional vaccinations will be required to provide protection from emerging variants as shown by the U.S. government's announcement recently that updated mRNA vaccines designed to protect against Omicron severance will be available in the coming days. We now have data to show that our oral tablet vaccine can increase immune responses and those who've received mRNA vaccines as well as those who have never been vaccinated against COVID-19. The data reported today also demonstrate that our oral candidate stimulated T-cell responses, again, not head-to-head, but we see levels similar to those reported from clinical studies of the mRNA vaccines. SARS-CoV-2-specific T-cell responses were observed in a majority of subjects after the second dose of the S-Only candidate. The T-cell responses observed in the 201 study were lower than those reported in the 101 study, confirming the effect of the end protein on T-cell responses. Taken together, the data reported today, at least at this stage of development, differentiate our oral tablet COVID-19 vaccine candidate from injectable vaccines with respect to safety and immune stimulation profiles. We believe the ability to stimulate broadly cross-reactive mucosal and serum antibody responses and to activate the antibody and T-cell components of the immune system may well have the potential to provide protection against COVID-19 that has not yet been achieved with the approved injected vaccines. If these findings are confirmed in later-stage studies, we believe that our oral tableted COVID-19 vaccine would provide important health and economic benefits to individuals, national health systems and the global public health community. Now let me turn for a minute to our strategy for continuing to advance our COVID-19 vaccine clinical program. Recent guidance from the U.S. Food and Drug Administration and other regulatory and global health organizations suggest that future COVID-19 vaccines may be bivalent and inclusive of an Omicron BA.4/5 construct. As previously announced, we're evaluating new Omicron-based constructs, both as Omicron-only monovalent vaccine candidates and as bivalent candidates in combination with our Wuhan constructs. These constructs will be evaluated in preclinical models this year and will advance to clinical trials in the first half of 2023. We believe this will allow us to move forward with the best possible vaccine constructs for our planned COVID-19 Omicron challenge study in the second half of 2023 with hVIVO as well as larger trials in the United States and internationally. I'll now turn this call over to Dr. Sean Tucker, my friend, our Chief Science Officer and our founder, will provide some additional context for how the data reported today support our COVID-19 program and our broader vaccine development efforts. Sean?

Thanks, James. As we indicated, we initiated the 201 study last October. We wanted to answer 2 important questions about the immune stimulating profile of the S-Only vaccine. And the first question was whether the S-Only construct could improve the serum antibody response observed from the 101 study, which was our S and N construct. And the second question was whether the S construct could boost responses in subjects who previously received an mRNA vaccine. And as James really showed in the data we've reported today, the answer to both those questions is a sounding yes, and that is fantastic. As James noted, the observed increase in mucosal IgA is very encouraging, and we believe the positive findings for multiple immunogenicity measurements may ultimately translate to enhance protection against infection with SARS-CoV-2. In particular, several leading academic researchers as well as members of the White House Summit on the Future of COVID-19 Vaccines, have talked about the potential of mucosal immune responses to block viral variants better than a serum-based response. Further, we and Duke University published a preclinical study in Science Translational Medicine showing that mucosal immune responses might do a better job in blocking transmission even to those that are unvaccinated. While we are still in early development, these results give us hope that we can improve on the current approach of frequent injections with limited effect on global COVID-19 disease. Previously reported data from the 101 study showed long-lasting cross-reactive IgA responses with that S+N vaccine candidates. While we haven't done time course studies yet for the S-Only candidates, the IgA mucosal responses we observed in this 201 study did cross-react with multiple viral variants, including Omicron subvariants, BA.4/5. Based on the 101 results, we would anticipate the IgA responses observed in the 201 study may be similarly long lasting. If we are right, this is important in the durability of the protection that the vaccine may provide. The 201 data also confirmed that the S -- sorry, the N-construct that plays an important role in stimulating T-cell responses and suggest that the inclusion of the N may also improve the T-cell responses to S. These data, in summary, suggest that a bivalent vaccine candidate comprising both the S-alone construct and the S+N construct could provide benefit by improving both the T-cells as well as the antibody responses. We believe the data reported today are clearly an important advance of our COVID-19 vaccine program, but they are equally important for validating our oral tablet vaccine platform. With this data, we have demonstrated a favorable safety and tolerability profile in more than 650 subjects and shown preliminary efficacy in 2 different viral respiratory indications, flu and we should say, immunogenicity with COVID-19. Collectively, these data advance our understanding of how to optimize development and deployment of our vaccine in our current programs and future product opportunities. We are really excited about the potential for the oral vaccine technology to transform approaches to the critical global health challenges and are confident we have the expertise and resource to realize this potential. I'll now turn this call back over to Andrei for some closing remarks.

Thank you, Sean. So early in the pandemic, many of us realized that an oral pill vaccine has the potential to revolutionize how we vaccinate people all around the world easily, quickly, painlessly with just a glass of water. Later, as coronavirus started to mutate and expose the limitations of the current generation needle vaccines, more and more people became increasingly excited about the prospects of mucosal vaccines. Those vaccines that harness more of our immune system with a potential to offer broader, longer-duration protection against current and emerging variant. The potential of both oral and mucosal vaccines seem so radical compared to today's injectable vaccines that it is natural that many wonder, can these vaccines become a reality? We believe they can and they will. We have previously shown -- sorry, we have previously shown that our oral pill vaccine can protect as well, if not better, against flu as a leading injectable vaccine in a Phase II human challenge study. We also have generated promising clinical data across multiple studies for our norovirus vaccine. So today, we add evidence for a third program with exciting clinical data supporting the great potential of our platform against COVID-19. And as we do so, we feel we are a step closer to realizing the full promise of oral pill vaccine. We, therefore, look forward to sharing additional updates with you in the months ahead as we progress our program. And with that, I'd like to thank everybody for joining our call today. And now we're going to move to the Q&A portion of the call. Operator?

[Operator Instructions] Our first question is coming from Charles Duncan from Cantor Fitzgerald.

Thanks, Andrei and team, for taking our questions and congratulations on the progress and sharing your perspectives on the data to date. I had a couple of questions, but just as a perspective biller, I guess the first question before I get into some of the more details is, why present this data now? And also, why not include any data slides? Are you soon to request a presentation at an upcoming clinical meeting? Or can you just help us understand why now?

This is Andrei. Yes, we heard you. I think either Sean or James, you mind taking that?

Yes, this is Sean. I'll take that. I felt like that we had enough data that was material and we needed to get it out there, and that's sort of what our lawyers thought. And from the standpoint of actually putting this forward, yes, I think you're right. It's because there's so much data in here, it's really important to get it out into a conference. And I think from our standpoint, we also want to add to it because there's still things we haven't done yet, for example, measure neutralizing antibody responses to Omicron. And those are the kind of things we want to put into a big package, make sure it's robust and then present it at a conference. So we did feel like that there was enough here that was material that we needed to get it out.

Okay. Appreciate that. Can you tell us a little bit about the sample size in terms of the number of subjects? And then do you have data from the other cohorts? It would seem to me that the -- a little bit older cohort might be of very much of interest and need here.

So Charles, for the sample size of the cohorts, again, we broke it down into naive subjects and to those who've been prior vaccinated with mRNAs. And when we look at those distributions, we look at different ages, 18 to 55 or 56 to 75, the more senior component. And then looking at the different doses, we looked at a 1x 10 to the 10 times 2 doses or 1x 10 to the 11 times 2 doses. Now initially, if you go on ClinicalTrials.gov, you'll see that the study itself was designed to be a little bit larger, right? And one of the issues of performing a clinical trial during a pandemic is that you get the subjects that are available, right? So in moving this forward, we adjusted our size of our study to give what we thought would be timely information on this first portion of our Phase II that would inform us on our program moving forward.

Okay. So the actual sample size, I'm not sure if I missed it. I might have spaced what you said.

So in terms of -- I can go through the different cohorts, if you would like, from those who are 18 to 55 years of age, who have a low dose who were naive. There were 12 subjects. And those that were a high dose naive and 18 to 55, we had 9. And those of the seniors who received the low dose, we had 8. From prior vaccinated and those who were aged 18 to 55 in a low dose, we had 13. And those who received the high dose in the 18 to 55, we had 12. And in the elderly component, in the low dose, we had 12. So a total of 66.

Got it. And then with regard to safety, it seems like that is clearly one of the points of differentiation in addition to the efficacy profile being different and perhaps value added. I guess I'm wondering, back to the observations regarding safety, no Grade 3 or greater safety observations for elicited events. Can you describe the gastrointestinal kind of symptoms or responses that were reported by patients on the first dosing and the second dosing? Any observations there?

I can't break it down by dosing in particular. I can tell you that there was infrequent Grade 1 or other GI symptoms, to include some nausea, no vomiting, some mild abdominal discomfort. But again, these are very small numbers, and they were short-lived, well tolerated. So I think the important thing from my standpoint, when I look at our safety profile is, one, how this compares to our platform, which is it's in sync with what we've seen with our other vaccinations or vaccine programs, but also how this sort of adds up to what we've seen as a community with the currently approved vaccines. There are many reports and personal experiences for those on the phone you may have had of being wiped out after the first or second dose of an approved injectable vaccine and really being nonfunctional in terms of the work or activities of daily living standpoint. We didn't see any of that. I hope that helps to clarify.

It does. It's super. It was definitely a personal experience. Can I ask you one last question, and then I'll hop back in the queue. And I think Andrei or Sean alluded to this, would you anticipate additional data to be reported later on this fall? And could that be in a peer reviewed or even a preprint form of a peer-reviewed journal article so we could see some of the data?

I think the plans are to publish this in the peer-reviewed literature. As far as the specific timing, sometimes it depends on which peer-reviewed literature format, you wish to push it forward out. Our goal is to continue to analyze a little more data as Sean had mentioned, and then certainly, to present this in a format at a meeting, et cetera, but also in the peer-reviewed literature. As far as specific timing, I can't say because that's also dependent on -- on the publication we choose.

That makes sense. Congrats on the data and progress thus far.

Next question is coming from Mayank Mamtani from B. Riley.

Congrats on this encouraging data. So first on serum antibody response, could you please also comment on any comparison you've done with convalescence? I know you had provided some perspective with the mRNA vaccines. And then relatedly, if you could also talk a little bit about the dose response. I know that is question also with the 101 study. So it looks like you did get a dose response. So can you just comment on that? And then I have a couple of follow-ups.

This is Sean. I'll take the question about the convalescence. So we haven't done a ton of work in convalescent sera in the past. We did a little bit. So I -- and we'll definitely try to do some better comparisons. I can tell you that the subjects that did walk through the door that looked like they had signs of being infected, but claim they didn't have an infection or an mRNA vaccine, their titers were somewhere in the 100 to 200 AU per ml range. So that's from the standpoint of microneutralization. And you did ask a good question about the IgA and IgG and I'll go through and look at that much more carefully. But certainly, from the subject that actually walked to the door that looked like their signatures of convalescence was in the 100 to 200 AU per ml range with, again, the caveat that that's a small N. And then you asked a question as well about dose response, Mayank?

Yes. Thank you.

Yes. So obviously, we're still small numbers in the study, but it does appear that more higher dose, more looks like it improve the responses. So if you're looking at groups that had a better increase, it definitely looks like it went up with those doses at the higher level than the people that took a lower dose. So with, again, the caveat the small N, when I'm talking about it, I'm talking about sera responses. So -- but yes, it looks like that there was a dose response for serum antibodies.

Yes, definitely looking forward to seeing those antibodies when you present the data. So then my next question is on IgA, mucosal immune response. So it looks like the threshold for responder rate is different from your study 101. So -- and also commenting on why is that, but also like I think you broke that previously in response specific to RBD and S response -- spike responses. Do you have that information with this data set? Or is that something you're working on still?

Sure. So yes, we've looked at RBD. We've looked at S. We've looked at to IgA responses against SARS-CoV-2, Wuhan. And then, of course, we've broken it down that we've been able to look as well at other coronaviruses, such as Omicron. I think that when we look at the response rate for this vaccine versus the 101, they're basically about the same. When you're using the same criteria, it's about 50%. Given, of course, deal -- the biggest issue with when you're looking at mucosal samples that you're taking material in, that's not exactly pristine like sera, you're talking about taking [indiscernible] in taking it and figuring out if there is a response. And so we feel comfortable saying that approximately 50% of the subjects respond in sera or -- sorry, in saliva or the nose. And again, it looks similar in terms of the profile from the 101 in terms of number of responders, the magnitude of responses with one caveat is that as -- when we did the 101 study, Mayank, keep in mind, people were certainly more naive from the standpoint of infection. We think the baseline has actually gone up in people over time in terms of their IgA response. So now you're talking about having to increase a bigger magnitude to call it a responder. So that may be part of the reason why the response rate doesn't -- hasn't changed. It's just because your baseline may actually be higher. And certainly, this is one of the things we saw in this study, too, Mayank, is that people that came in with a high sera response, say, like they had a high -- an IgA response in the hundreds of thousands upon vaccination. Those didn't go up, but didn't really to any extent. I mean maybe that's a limit to the assay. But if you talk about people that came in with low IgA responses in the sera, those are the people that seem to have a higher response rate. And again, we'll break this out in publication in presentations in the coming fall.

Yes, that makes a lot of sense. And then just a final question on next step. And specifically, as the bar you're setting for your Omicron variant-specific vaccine, how would you characterize that based on the preclinical models that you're running, but also operationally, how seamlessly again that be integrated into your Phase II protocol like you did with the S-Only because you do have a protocol, right, which goes up to 1,000 subjects with Part 2. So is that Omicron variant-specific vaccine just kind of be involved whenever that's ready next year? And then in parallel, you can also have the challenge study running second half of next year. Can you just clarify sort of how you're thinking about all this?

Sure. This is James. So that Part 2 of our Phase II protocol that you mentioned, that was designed over a year ago and assuming the construct we wanted to push forward with is the current Wuhan-based S-Only construct. The world has changed a lot since then with the waves of Omicron, changing government regulatory guidance and our understanding -- our own understanding of how our S and -- our S and N constructs perform clinically. Taking all that into account, the important next steps clinically are for us to compare the new Omicron-based constructs clinically as monovalent and potentially bivalent constructs and then doing the Omicron human challenge study in the U.K. with the best construct moving forward.

Your next question is coming from Roger Song from Jefferies.

Great. A couple of -- from us as well. So the first one is the -- for neutralizing antibody. I think Andrei or James, you provided some perspective for the mRNA 1.5 to 1.9-fold increase for the booster. And we know days, probably this is the benchmark for the homologous booster, but they're also slightly higher for heterologous booster for mRNA. Maybe just -- the real question is, so what is your goal for the neutralizing antibody sera as a booster, given you also have some benefit for the IgA and some other T-cell and cross-reactivity here?

Yes, I'll take this question. So I think the goal with the neutralizing antibodies was basically to show that we could provide something that was a reasonably equivalent sera response. And as you pointed out, the platform itself lends itself better from the standpoint potentially of T-cells and obviously mucosal. So we think there would be added benefit. I mean, I think from our standpoint, the fact that we're able to show some boosting is really important for us, and it shows that we complement the mRNA. So I think I'm not sure if there's a set benchmark but at least people can kind of look at the neutralizing antibodies and get a sense that based on other work that a minimum amount of protection is going to be afforded. So I think that's one thing. And then, of course, you asked the question about variant-specific looking at that, and that's something we're going to do, again, looking at more of the whole platform. Obviously, we have done the work in terms of looking and showing that we can make an Omicron response in the nose. Everybody that had a Wuhan response, had an Omicron response in terms of increased IgA and we're going to look as well in the sera to see -- because I don't -- this is something that you pointed out potentially in it as well is that there may not be as much room to increase greatly in terms of Wuhan, you maybe just maxed out but one of the things that could happen is you drag up the variant specific much to a greater extent. And that's something we'll figure out as we go forward. Did -- I hope I answered your question?

Yes, that's helpful. Maybe just a follow-up on the variants. So far, do you have the immunogenicity difference between the ancestral Wuhan stream and different variants in the -- even other coronavirus on the IgA and IgG and neutralizing antibody level?

Yes. So the short answer is we have done that only for IgA responses in mucosal samples because those assays were well developed. We definitely know certainly from the 101 study that if anybody got a response against Wuhan, S or RBD, those people also increased against Omicron and any S and RBD, that's no problem. Same thing we saw in this study that we saw increases in the antibody response to Wuhan, those same subjects have an increase against Omicron, SARS-CoV-1 and other things that we've tested. You made a good point. Have you looked at neutralizing antibodies? Our plan is to look at the neutralizing antibodies, both in the base of samples and saliva samples as well as in the serum against Omicron. We had this planned on doing that thing very quickly because we thought we were going to focus on mucosal response but now we have such strong data on the news that we're going to basically look at it very soon. So that's coming up. And yes, it's a good question.

Excellent. Maybe just a last one from us is the IgA. I understand you -- this time, you showed the 50% for the -- and this still 1.5-fold increase, slightly lower than last time I think you made a point, maybe the baseline higher. But so a similar question. What is in your current thinking, what will be considered as the good responder -- response rate for IgA considering you probably want to prevent the transmission or infection down the road when you do the challenge study?

I'll let James answer the question in terms of the challenge study. But I think from our standpoint, what we want to be able to do is basically see that we got a significant number of people, greater than 50%, having a measurable IgA response. And again, because it's so hard to basically see changes, we feel like that would be important and again, this is sort of where we're at. James can probably talk -- and again, one of the things that -- one of the things I should point out is that, we believe that even if we're not measuring an IgA response, there could be still something there. One of the -- we like to look at the quality of the antibodies that were being made, something like neutralizing antibodies in the nose. I think you -- we did publish a study that said that one of the things we saw is that of the -- when we look near to our IgA responses in the 101 study with convalescence, the equivalent amounts were being produced in the nose, but the quality in terms of neutralizing potential was higher in the people that have been vaccinated. And those another thing that we want to basically look at is, are we improving the quality of those antibodies as well? I'll let James answer the question about the challenge study.

Thanks, Sean. So Roger, in the planned challenge study, what we'll be looking at is the mucosal immune responses, after immunization, and we'll be looking at the potential impact that we'll have on viral shedding. And I think that they're related there. I think one of the -- one of the pieces to also hallmark and the question we've been asked by others is how long does that immune response last, the durability? And Sean, I don't want to misspeak with so many analysts on the phone, but I think we have data from that 101 study that it goes out. Is it a year?

Yes. It's up to a year, we've looked and it looks like it's still durable.

Right. So I think that the initial responses and their impact on viral shedding is one of the data points we plan to collect when we move forward with hVIVO on the Omicron challenge. And then the durability piece, again, we'll continue to look at that, but we've gotten, I think, very positive data on our previous study.

Excellent. Thanks and congrats on the data.

And Roger, this is Andrei. I wanted to add to what my colleague said on your first question regarding the neutralizing antibodies. So -- as we said before, I want to caveat this by saying that we are still analyzing this data and processing it. So rather than give you an answer, I'll turn this around to some interesting questions that we are trying to answer. So does this data suggest that our oral tablet vaccine as a booster gives you a similar serum immune response as the injectable vaccines? And would that alone mean that you could expect similar efficacy? And then aside from that, what's interesting is that the vaccine seems to activate mucosal immunity and generate T-cell responses. So you could look at the set of response as being, one, which may or may not be similar to what injectable vaccines do, but then also you have in addition to that, the mucosal response and the T-cell response. So the totality of that we believe is what's very differentiating and very exciting too. Now as far as the strength of the serum responses that we've observed, I think my colleagues, James and Sean, provided some data points you can piece the data together here as far as fold increases from baseline and also something that can help us triangulate fold increases from convalescent plasma. Again, we need to do more work there. But internally, we are very encouraged by what we think we are seeing here.

Next question is coming from Kumar Raja from Brookline Capital Markets.

I'm [ Shubhendu ] for Kumar. Congratulations on the data. So there is some evidence that previous infection or vaccination or both, they can offer protection to a different extent against the different variants, say, Delta and Omicron. So with regard to the present Phase II data, what are your thoughts on the ability of the S-Only to protect against the different variants? Is it going to be kind of uniform protection? Or are we expecting differential protection depending on the strain that impacts it?

I'll take that one to start, Sean.

Go ahead, James.

And if you want to back clean up? Yes. So -- so as you know, this study wasn't built for efficacy, right, but safety and with secondary immune readouts. And I think what we've shown is along with being safe and well tolerated because vaccine did have immune responses. And when we looked at the -- certainly the mucosal immune responses, we saw cross-reactivity across for those who responded, they're responding not just to the Wuhan strain but they responded to the Omicron variants as well, right? What that means in terms of efficacy, that will be a follow-on study. So I don't want to go too far down that path. But Sean, did you want to add any specific granularity there?

Yes, I'll just add to it. Obviously, we've seen some really important and meaningful responses in the mucosal samples that shows -- that suggest that we're getting a very cross-reactive response. I think one of the best things that we can do in terms of testing it and how it impacts is to do those challenge studies and eventually follow-on studies for -- in Phase III. One of the things about the challenge model is that it doesn't take very many of SARS-CoV-2 viruses to sort of get infection at least from the first time. So we think that a little bit of a mucosal response could go a long way in terms of providing protection. With the caveat, of course, we're going to do the study and show it -- so from the mucosal standpoint cross-reactivity is good. On the other side of the question, I think one of the things that has been noted with the mRNA vaccine, you get a very, very strong sera response that wanes very quickly and it seems it's much more -- not strain, it's much more strain specific. We don't know what the kinetics of our sera responses are, whether they're going to be more durable, and we're going to look to see how well they are in terms of cross-reactivity as well going forward.

Thank you. At this point, I'd like to turn the floor back over to Ed for further questions.

Thank you. Many of our questions have been answered that have been asked via our IR portal. I have a few, though, that the first one is for Sean. How does this strategy and these data compared to other mucosal vaccine strategies? And James, please feel free to go into.

Sure. Obviously, there's been a lot of interest in the mucosal approach. There's been announced a couple of studies that were oral, but no data in humans. And there's been some work that people are working on for intranasal delivery as well. So far, I haven't seen anything super compelling when it comes to intranasal vaccine approaches, showing a mucosal response. There's a couple of things. One of the things I should note is that one of our competitors, Altimmune was one of the best in the world from intranasal accommodated adenovirus. And when they did their Phase I study, they didn't find that it worked very well. So I -- it's an interesting point, and it may be that they're putting vaccines are in the [indiscernible] for something like SARS-CoV-2 where people have been exposed to a lot of coronaviruses may impact the ability for it to work. If James has additional info, that would be great.

No Sean, I think you sort of hit it on the head, right? And when it comes to oral tableted vaccines that are thermostable and against COVID being in clinical trials in a Phase II, we're the leader here. So some of this is uncharted territory in terms of where we are. And I think we've laid out a good plan of where we're going.

Okay. Next question. This one is for James. The company has mentioned a follow-on clinical trial in India. Can you give us some information about the status of the study and the plans for the company?

Sure. So -- and I touched on this a little bit, I think, in the presentation when we're chatting, but the study for our S-Only COVID-19 vaccine construct in India was initially planned over 10 months ago. And that said, a lot has changed since that time. And as we've announced, there are -- we are now developing new Omicron-based constructs. We've also learned a lot since that time, specifically some of the data we've presented here about our S construct and our S+N construct and how they might fit into our development strategy. We'll be refining our future vaccine studies based on outcomes from our proposed Phase I studies involving improved constructs, either alone or as a bivalent approach potentially in H1 of next year. We're committed to developing our COVID-19 vaccine, both in the United States and internationally. And a key part of our development program now is the U.K. Omicron challenge study which we announced should be in the second half of '23.

Thanks. A question for Sean. Why aren't the results in this study the same as seen in the nonhuman primate study that you conducted?

Yes. Obviously, very people -- humans are not large monkeys. They certainly are different. One of the things that I'd like to point out is that when we do NHP studies or nonhuman primate studies is that those monkeys have really never seen coronaviruses before and so there's almost no background. When you give your vaccine, you can see a very strong response. I can tell you that humans, particularly if you have young kids around, they get coronavirus infections every 2 to 4 months, several times a year. And the background levels of antibodies and things in humans is a lot higher. So when you -- and so from that standpoint, it definitely impacts the ability of your vaccine to be -- add on to that immune response. Even if SARS-CoV-2 is a little bit specific in some ways, there's definitely more background when it comes to the assays and what you're measuring and looking at the changes. So there's definitely a difference just from the standpoint of your exposures and that makes a big difference as you're trying to measure these things.

Thanks. The next question is for James. Given the data that we presented today, what is the path to an EUA and what does it look like?

I'll pull out my crystal ball, right? So really, it depends on a few different factors, right? We'll certainly leverage how the U.K. challenge study results look and that data will be very important in moving this program forward. But it will also depend on the state of the pandemic at that time. If we as a society are unlucky and we see a particularly voracious strain or 2, highly contagious or high degree of morbidity and mortality, then I think there'll be more of an appetite to move forward with our next-generation solutions to this pandemic. If the strains continue to come out, I think that EUA might be -- and aren't particularly deadly, there may be less emphasis on. It's very difficult to know. There are some things we do know, right? We know that there are going to be more variants coming out. The coronavirus has a very sloppy gene editor. So it's not if, it's when. And most experts would say it's 3 to 4 variant strains per year is what you should be considering, right? And right now, we're showing a cross-reactivity with our mucosal approach. We're just not seeing that with the standard injectables that really, I think, harken an IgG serum response. So you don't have that protection of prior to infection getting a handle or a hole on the virus and/or decreasing transmission. So I think these are very important things that certainly if proven out in larger studies, would portend a very viable market for our program moving forward.

Okay. I have no more questions. So this concludes the question-and-answer session at this time.

Thank you. Are there any further closing comments? If not, then that concludes today's teleconference and webcast. You may disconnect your lines at this time, and have a wonderful day. We thank you for your participation today.