Good day, and welcome to the Novavax COVID-19 Vaccine Data Review Conference Call. All participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star, then one on your telephone keypad. To withdraw your question, please press star then two. Please note this event is being recorded. I would now like to turn the conference over to Silvia Taylor, Senior VP of Global Corporate Affairs and Investor Relations. Please go ahead.
Good evening, everyone, and thank you to all of you who have joined us for today's call to discuss Novavax's initial Omicron cross-reactivity data from our COVID-19 booster and adolescent studies. A press release announcing our results is currently available on our website at novavax.com, and an audio archive of this conference call will be available on our website later today. Please also note that we have posted the slides that we are using during this evening's call at novavax.com/events. Joining me today for discussion and a Q&A period are Stan Erck, President and CEO, Dr. Filip Dubovsky, Chief Medical Officer, Dr. Greg Glenn, President of R&D, and John Trizzino, Chief Commercial Officer and Chief Business Officer. Before we begin with prepared remarks, I need to remind you that we will be making forward-looking statements during this teleconference, which are based on our current expectations and beliefs.
For example, statements relating to future financial or business performance, conditions, or strategy, including expectations regarding revenue, operating expenses, cash usage, clinical development of our vaccine candidates, timing of future regulatory filings and actions, and other anticipated milestones are all forward-looking statements. Novavax cautions that these forward-looking statements are subject to numerous assumptions, risks, and uncertainties which change over time, and actual results could differ materially from what is described in such statements. We encourage you to consult the risk factors discussed in our SEC filings for additional detail. I'd now like to hand the call over to Stan.
Thank you. Thank you, Silvia. Thanks everybody for joining the call. We're on a little bit of a tight timeline today, but we'll be brief. Just noting the number of announcements that we've had over the past few weeks, including product authorizations in Europe with the WHO in Indonesia. Product shipments, our first shipments of product to Indonesia, followed by not insignificantly starting up a new trial to test our vaccine as a booster yesterday. On top of all that, we have some important news, particularly given the prominence of Omicron currently. Some data on how our vaccine performs against this variant.
I'll turn it over to Filip Dubovsky, our Chief Medical Officer, who can go through the slides for you. Thank you.
Okay, let's skip to slide three. This really just lays out the clinical development plan. Those of you who follow us know this. We have two phase III studies, 30,000 people and 15,000 people. This was the basis of our efficacy data that we've gotten our approvals on. We also had a phase II study in South Africa and importantly, a phase I, phase II study in Australia that this is our boosting study. We continued these participants through and boosted them, and this is some of the data we'll be sharing today. I do want to remind you of the efficacy we saw in our two phase III studies. They were remarkably consistent, 89.7% versus 90% overall.
The important numbers to look at here are the matched strains. 96% for the U.K. study and 100% for the U.S. study, as well as for the Alpha, 86% in the U.K. and 93% in the U.S. These are important because they serve as benchmarks when you compare the immune responses against the variants we'll be looking at today. I guess one more point I'd like to make is that in the U.S. study, where we had the broadest number of variants circulating, we actually had complete protection for moderate and severe disease against all variants. What kind of assays have we developed? We're gonna be sharing data from three kinds of assays. Let's move to slide five now.
We have a binding assay, which is just an anti-spike IgG ELISA. This measures the ability of the antibody that's induced by the vaccine to bind to the spike protein. This is a fit-for-purpose assay that's being conducted at Novavax Discovery Labs. We have a human ACE2 inhibition assay, and this is a functional assay. Some of you may have seen data from this before, and we've published this. What this assay does is probes the ability for the antibody to prevent the receptor binding domain of the spike protein from actually binding to the receptor. We know this is a required event for the virus to invade the cells. This is a very stringent assay, as we've talked about previously. This is also conducted in the Novavax Discovery Labs.
Finally, we have a wild type neutralization assay, and this is another functional assay that measures the ability of the antibody to prevent the varied viruses from invading cells. This is conducted by our academic partner, the Matthew Frieman Lab at the University of Maryland School of Medicine. This is also a fit-for-purpose assay. Some of the other immune assays we've published on before are validated assays, and they are different, and we'll look into different values. The data we have prepared to review today come from two studies. One of them is the U.S.-Australia phase II boosting study, and we have data from both after 2 doses as well as 3 doses with a 6-month boost. There we have the anti-spike IgG, the human ACE2 receptor inhibition, as well as a variant wild type neutralization.
We also have a little bit of data from the adolescent phase III study, and this is just data after two doses. Those participants haven't been boosted yet. For that we have variant IgG as well as human ACE2 receptor inhibition. Let's go to slide seven. This is just to remind you of the design for the phase II study. This is a study that recruited 1,288 adults in the U.S. and Australia. I've outlined here the arm that we boosted and will be describing today. Everyone received two doses at day 0 and 21, and then a portion of the subjects received a third dose at day 189, at 6 months.
We continue to boost these subjects, and we have boosting data that's being developed now, boosting at 1 year, and that data should be available sometime next year. Let's move to slide 8. Slide 8 is data which comes from our clinical immunology lab. This is validated assays, which are different from the assays we'll be describing in the near future. What I've done here is transpose the immune responses we saw in the U.K. phase III study on the left, the PREVENT-19 U.S. Mexico study in the middle, and the boosting data we saw from the 6 months on the right-hand side. I've overlaid the efficacy on top of that for both the prototype and Alpha strain.
What you can see is that with a third dose, we got 3.7 to 4-fold increase of antibody compared to what we saw in those two studies where we had high levels of efficacy. Let's move to slide 9. This is a companion slide which describes the wild-type neutralization response. Once again, this is an assay done at 360biolabs, so different from the assays we'll be looking at, so don't compare the values. What you can see once again is a third dose boosted the immune response 4.6 to 5.5-fold above that which we saw in the phase III studies once again with high levels of efficacy against variants as well as prototype strains.
Our first new data slide is slide 10, and what this shows is the variant-specific IgG after two doses and three doses. The left-hand side is the two-dose data, and that's day 35, and the right-hand side is day 217, so that's 20 days after the 6-month boost. We saw a variant-specific IgG response against all the variants after two doses. In fact, we had 100% seroconversion against all the variants after two doses. You can see we had a significant bump with a third dose, 5.4 to 11.1-fold above the peak responses we saw at day 35. Well, it starts with the two prototype and Alpha bars.
Just to remind you, those are the ones that we have efficacy with, so you can kind of use those as a benchmark, although direct comparisons of course are tricky. Let's move to slide 11. Slide 11 shows the ACE2 inhibition responses. Once again, you can see we detected ACE2 inhibition responses against all the variants after two vaccinations. We have a significant bump after the third dose. You can see that after three doses, those levels were pretty much comparable or superior to that which we saw against the prototype with two doses where we saw efficacy. You'll notice that Omicron is lower than the others. This is completely expected.
Remember, the Omicron has many mutations in the receptor binding domain, and that's what really this assay measures, is ability for the spike to bind the ACE2. We would anticipate having a lower response against Omicron. However, the third dose really does correct the magnitude of the immune response to Omicron as well as the other variants. Let's move to slide 12. Slide 12 shows the wild type neutralization responses. This assay done at the University of Maryland is a 99% neutralization response. Some other people run this as a 50%, but this is a bit more stringent. What you have compared for prototype Delta and Omicron is the day 35 responses versus the day 217 responses.
You can see in all three instances, you get a boost with a third dose up to quite high levels. The difference between the prototype and the Omicron is less than a fourfold difference after two doses. Although I should caution you, these are different viruses, so comparing between various viruses in this assay should be done with caution. I guess you can also see that the day 217 responses are really comparable to those that we saw after two doses on day 35, suggesting that efficacy will be maintained with a three-dose schedule. Let's turn to the PREVENT-19 study. This is the overall design. Once again, this is a study where we had 30,000 adults.
Two-thirds of them received vaccine, one-third received placebo, and then we crossed them over, so those who received vaccine initially got placebo, and those who received placebo initially got vaccine. We did a sub-study for that, including adolescents, and that had 2,248 adolescents, and once again, two-thirds received vaccine and one-third received placebo. The data we'll be revealing is the data that we generated for the immune responses after two doses in the vaccine group. Let's turn to slide 15. What you see on slide 15 is the anti-spike IgG for all the variants. This is after two doses once again. You can see that we had very high levels of antibody against all the variants, including Omicron.
In fact, the immune responses in adolescents were 2 to 3-fold higher than that which we saw in adults. Clearly, since we had 100% seroconversion in adults, we had 100% seroconversion against all the variants in these adolescents as well. Let's go to slide 16. Slide 16 shows the ACE2 inhibition data. Once again, we saw values which were higher than that in adults, 2.4 to 4-fold higher than we saw in adults. These results also compare quite favorably to what you can achieve with two doses in adults, that which we did in the phase III study in the U.S. and U.K. I want to take the opportunity to reiterate what our next steps are for the Omicron vaccine development.
Given that we do have an ongoing pandemic, we're obviously developing an Omicron-specific vaccine. The GMP manufacturing is expected to begin soon, and we expect to begin clinical studies in the first quarter of the new year with our material. Let me go to slide 18, which tries to sum up kind of what I've described today. From our phase III studies, we demonstrated protective efficacy against a broad array of variants that circulated while we conducted those studies in the U.S., Mexico, as well as the U.K. For our anti-spike IgG response, we saw 100% seroconversion to prototype Alpha, Beta, Delta, and Omicron after two doses.
Furthermore, we boosted these responses 5.4-fold for prototype up to 9.3-fold for Omicron, and that's above the peak responses seen after the two-dose primary vaccination schedule. This represents a 61-fold for prototype and a 73-fold for Omicron increase just prior to the boosting with dose three. For the human ACE2 inhibition assay, we observed ACE2 activity against the prototype, Alpha, Beta, Delta, and Omicron after two doses. After we boosted with a third dose, we achieved 100% seroconversion against all variants of the population. These boosted titers increased from 6-fold for the prototype up to 19.9-fold for Omicron compared to the peak responses following the two-dose primary series.
This level really represented a 54-fold for the prototype and a 24-fold for Delta and a 36-fold for Omicron increase from just prior to the boosting dose given at 6 months. For the wild type neutralization assay, I want to reiterate, this is a 99% wild type assay, we observed neutralization after 2 doses for prototype Delta and Omicron. After 2 doses, the Omicron wild type neut response was a little bit less than 4-fold lower than for the prototype. We saw significant increases after boosting to both Delta and Omicron, and these were comparable to the levels we saw in the U.S. and U.K. study as far as absolute magnitudes of neuts.
Finally, I'll share with you some immune responses in our adolescents, and they very much matched what we saw for the IgG and HAI responses in the adults, except they were 2 to 4-fold higher following two doses of vaccine. With that's the end of my prepared remarks. I will turn it now over to the operator for Q&A.
Thank you.
Yeah, this-
We will now be-
Sorry, this is Stan.
Thanks.
I just want to make one remark before we do turn it over to Q&A. I think that the audience should recognize that this is yet another demonstration of the power of our technology platform. We get very broadly neutralizing antibodies through the combination of our adjuvant and recombinant nanoparticle and in the case of COVID, that we've done that yet again. With that, I'll turn it over to the operator for Q&A.
Thank you. We will now begin the question and answer session. To ask a question, you may press star then one on your telephone keypad. If you're using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star then two. At this time, we will pause momentarily to assemble our roster. Our first question comes from Kelechi Chikere with Jefferies. Please go ahead.
Thank you. Just a couple of questions on my end. I guess first, can you help put into context the data that you're presenting here and the data that we've seen for the mRNA vaccines, particularly as it relates to the fold reduction after two doses versus Omicron and the fold increase after the third dose? Any additional color there or context there will be really helpful. I guess my second question is just related to, can you speak to whether you've foregone your decision to move forward with a multivalent vaccine or is that something that you could still do in Q1?
Maybe I'll take the first question and Greg can jump in as well. It's very difficult. It's, in fact, more than difficult. It's possibly fraught with error to try to compare immune responses with using different assays, right? I think within an assay it's a fair comparison, but when you start comparing things like fold rises, like you mentioned, we had a little bit less than a four-fold decrease for our wild type neuts, compared to some of the others which may or may not have been higher. Same for the fold increase after boosting. I'm not sure that I can say a lot more. Greg, do you have an opinion on this or a view?
Well, yeah, I agree with that. It's, you know, the absolute numbers, the magnitudes are a little. That's difficult to say. However, I would point out that what Filip presented is data on very stringent assays. The inhibition assay is a mechanistic assay that requires a very high affinity antibody to block binding of spike to hACE2. We're detecting antibodies that do that for Omicron after the two-dose regimen. Similarly, with the wild type assay, we're detecting neutralizing antibodies, again, measured stringently with a 99% level of neutralization against Omicron after two doses. After three doses, they're very robust, and they look similar to the kind of immune responses we had in our phase III trial. So I think this is very promising. Obviously, we're gonna be interested.
You know, we just started a booster trial. There's gonna be some surveillance that is boosting our subjects from our phase III trial, so we'll be able to collect some additional data there. You know, as far as other variants, we're keeping all of our options open. I will say we've made very good progress moving from you know, the identification of Omicron. We have now cloned, expressed, and characterized our nanoparticle vaccine, and the key event to sort of trigger the GMP manufacturers to provide the recombinant virus, baculovirus, which we've done. We're moving very fast to develop clinical data on Omicron and keeping our options open. It does seem, at this point, very wise to push hard to get Omicron tested in the clinic.
Yeah. Just that, I mean, there's no specific issue with making a bivalent vaccine. Certainly that's within our power to do. It's just in the first instance, we wanna go with a strain change kind of approach for licensure. In that case, using a monovalent will just be simpler and faster.
Okay. All right. Thank you.
Our next question comes from Charles Duncan with Cantor Fitzgerald. Please go ahead.
Hey, good afternoon, Stan and team. Thanks for taking my questions. Congratulations on these observations today. I just wanted to maybe follow up on the last question, and that is, you know, if you consider the observations from the different assays, do you favor one over any of the others in terms of having predictive value for clinical efficacy? I had a follow-up with regard to the adolescent component of PREVENT-19. I'm wondering if you could provide us any observations in terms of safety, particularly myocarditis or any other safety observations from that cohort.
Let me start off with the assays and then maybe Greg can jump in once again. I think the assays tell you different things, right? That's why, for instance, you saw a big change in the human ACE2 inhibition, and that's because that's where that particular variant holds a lot of its mutations. We know, and we've done this for a while, that we generate immune responses that are neutralizing, that aren't specific to the RBD, that are on different parts of the spike. That's why the wild type neuts, you know, are personally my favorite view to look at it. However, the wild type neuts suffer from having different viruses in each of them. As far as being comparable between various viruses, that's a bit trickier.
Whereas the ACE2 is in my opinion probably a bit more robust when you look variant to variant. Greg, do you have an opinion on that?
I just would say the anti-spike IgG is unique to our technology because we're the only group to make a full-length glycoprotein with a transmembrane domain. That, in my view, affects the whole structure, sort of like a string of pearls. I really like seeing that measure because there are different mechanistic contributions to, you know, ameliorating or eliminating while preventing disease. I feel like it's a nice picture to see, and of course, it's more sensitive with anti-spike IgG. Together we see, you know, two mechanistic assays and the overall overarching assay of immune responses to spike. I think it's, you know, really robust and informative.
I think, you know, my prediction at the end of the day, they'll all have some level of predictive value for protection.
Okay. That's helpful, Filip.
And as far-
Greg.
As far as your second question, do you wanna-
Yep.
Follow up with that?
No, please.
As far as your second question about the safety, we haven't discussed safety or efficacy out of the adolescent study. However, you may wanna look at the SmPC that's published by the EMA, and there our ADRs are listed, and there’s no cardiac finding, at least in the view of the EMA.
Okay, great. Just one quick follow-up regarding the booster study from PREVENT-19. I'm wondering if you've begun to enroll patients or if not, when you intend to, and is there a data milestone in terms of number of patients or something like that? Can you project timing?
Yeah. We started vaccinating a couple days ago, and more and more sites are coming on board. It's a big study, obviously. You know, the volunteers, the participants have to agree to enter the boosting portion. It is unclear as to exactly what the final denominator is gonna be. That being said, you know, the vast majority still did continue in the study. They didn't drop out, even those who sought vaccination with emergency use authorized vaccine. Assuming those people, participants do choose to volunteer, we're gonna have the ability to look at a heterologous as well as homologous boosting that population. Furthermore, this is designed as an efficacy study, so we are gonna be collecting endpoints after boosting.
The analysis of that is gonna be very tricky because we don't have a comparator group anymore. We're gonna have to do comparison from within the study, which is gonna obviously be confounded by emergence of new variants and force of infection.
Interesting. Okay. Thank you for taking our questions and the updates.
Again, if you'd like to ask a question, please press star then one. Our next question comes from Mayank Mamtani with B. Riley. Please go ahead.
Good afternoon, team. Thanks for taking our questions, and appreciate you turning around this data quickly. In just diving a little deeper into the immune response learnings that we have and obviously, you know, trying to compare that against both the quality and magnitude of, you know, responses we have seen from, you know, your peers. Are you able to provide us with the specific fold-utilizing titers pre and post-booster, like you have for the, you know, IgG, like you've provided that 74-fold increase? Are you able to provide that on the neutralizing titers maybe?
You know what? We don't have that data formatted in that way. So no.
Okay.
I just have the data tables.
We'll try to do that math looking at that chart. But just maybe if you are able to comment on just high level at, you know, at six months, what you're learning about, you know, what your boost could do, you know, given what you've learned from the primary vaccine series. As you can imagine, the rationale for my question is, you know, getting into the data that we have seen from mRNAs where there's absolutely no protection at three months, specific to Omicron, in spite, despite the boost.
Is there anything different that we should expect from the platform that, you know, as you follow along for longer, the sera for subjects that are vaccinated with the booster, with the Novavax booster?
I mean, my guess is that we're gonna be quite practical about that and get our real-world evidence to get a great feel for that. I just went back, while you were asking your question, to see what we did have on the neutralizing titer previous to boost, and we didn't actually run those samples. This is a very time-consuming assay, and, you know, to do the wild type neuts and the samples which we'll run, which are the values that I showed you. So we don't have the pre and post boost data available. I don't know. I mean, Greg, do you wanna speculate what we do know about our immune responses? Are they broader than many? Stan touched on this before.
We know even from our flu data that we're able to induce HAIs against a very broad range of drift strains as well as ancestral strains. We see this as a strength of the platform. You know, if you just think back on the efficacy data we showed in the U.S., we had very high levels of efficacy against all the variants which floated around, which were basically drift variants, and a complete protection against moderate and severe disease in that study. I mean, Greg, do you have a sense of is there a way to guess when we need to apply different doses? I don't think so.
Yeah, it's not easy to tell. What you can see from the data Filip showed today is what we have been saying for several years, that when you make a spike or a surface protein that is normally in a virus packed in a surface, we present these things in a different way. We have absolute fidelity. We have, I think, something unique amongst vaccines, is we make the full-length spike protein, and we can actually study it. Now, I know we'll be following up on some COVID-specific information, but if you look back at flu, we've shown that we have broadly neutralizing monoclonal antibodies. We know the epitopes they bind to. We know we make antibodies in humans to these broadly neutralizing epitopes.
These sort of responses are something we can expect based on what we know about our construct and our technology. The beauty of the adjuvant, I think Stan mentioned this, is that this you know really fans the flame and increases the immune responses to conserved epitopes. I think that's what's driving these broadly cross-neutralizing antibodies. It is pretty interesting to me to see how, you know, at the third dose, how everything kind of catches up and gets very similar. I think that's the strength of our technology. We have a lot of good data, and I'm sure in the future we'll present on this phenomenon with more, you know, science around the structure and function.
It is an advantage of our technology, so we can actually study that in detail from our vaccine, and I think the strength of our technology.
Great. Just if I can squeeze in one follow-up. Do we have data from your Beta variant-specific vaccine? You know, I'm just thinking as you think about that multivariant vaccine construct. Looks like, you know, Beta does the efficacy goes down the most with Beta and obviously with Omicron. Like, how much does that data play a role in sort of your call on, you know, what variant constructs go into that multivariant vaccine later this year?
Well, some of the key mutations with Beta are in the Omicron, right? I think, again, maybe you can look forward to a science day and, you know, we just have some real specifics on that. It's clear we have those epitopes that make antibodies to them. To me, you know, this is just again showing how broad the technology is. I think we, you know, we're seeing Omicron is as far away from the prototype as anything, and we do see some diminution due to that. That's why we're, you know, we're moving ahead, and we're doing this very quickly, I might add, with an Omicron, you know, spike protein vaccine.
Right now it's not entirely clear how that might be deployed, but we wanna show that we can make it.
This, you know, this data suggests it's probably wise to try to make it and see how it looks clinically. You know, I-
But I-
I look at-
Yeah.
Go ahead.
Greg, I guess that you just tickled my brain, and a point I'd like to add is after three doses, irrespective of the variants we probed, you know, our immune responses were very robust. They were quite high. So my sense is that an optimal product may need to include variants, but if you just look back at either the IgG or the human ACE2 following a third dose, this is a pretty very broad immune response, which really is comparable to what we saw in the phase III studies with two doses against the prototype. So I mean, I guess my sense is a little bit as long as you get a third dose in, you have a high chance of having good outcome.
These changes are meaningful immune escape changes. Against that background, I think the vaccine approach is really strong.
Great. Thanks so much for taking our question, and I'll hop back in the queue.
This concludes our question and answer session. I would like to turn the conference back over to Stan Erck for any closing remarks.
Well, thanks, everybody, for signing on at what is sort of the last minute. We thought the data were significant enough in this current environment, and this is initial data that we're giving you. We have more data to come. We've got new trials starting, and look forward to reporting on those throughout, well, as we transition into the new year. Thanks again.
The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.