Novavax, Inc. (NVAX) Earnings Call Transcript & Summary

Ladies and gentlemen, thank you for standing by, and welcome to the call on the results from the pediatric expansion of the Novavax PREVENT-19 pivotal Phase III trial. [Operator Instructions] Please be advised that today's conference call is being recorded, but the recording will not be publicly distributed. I would now like to turn the conference over to Silvia Taylor, Senior Vice President of Global Corporate Affairs. You may begin.

Good evening, everyone, and thank you to all of you who have joined today's call. We're delighted to share with you today the results from the adolescent portion of our PREVENT-19 pivotal Phase III trial. 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 us ing during this evening's call at novavax.com/events. Joining me today for discussion and the Q&A period are: 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. With that, I'd now like to turn it over to Filip, beginning on Slide 3. Filip?

Thank you, Silvia. So I'm going to start on Slide 3, describing the PREVENT-19 study. This was the adult portion of our study and the adolescent portion is a add-on or expansion of this study. So you remember, this study had 30,000 adults, greater than 18 years of age, 2/3 of whom received vaccine and 1/3 received placebo, and we follow them for efficacy. Our primary efficacy endpoint is PCR symptomatic mild, moderate or severe disease occurring 7 days after the second dose. If you remember, our overall efficacy was 90.4% with a 100% efficacy against match strain, and those are the strains most similar to the prototype strain the vaccine was built against. Additionally, we had 92.6% efficacy against variant, and that's all variants. And we had a number of different variants within the study. In fact, we saw alpha, beta, gamma, epsilon, iota, kappa, zeta, as a group overall. And finally, I want to remind you that this vaccine worked very well against severe disease. We had no moderate or severe disease in the vaccine group, which yielded an efficacy estimate of 100%. So let's move to Slide 4, and Slide 4 describes the adolescent expansion. In this portion of the study, we randomized 2,200 adolescents, 18 -- 12 to 18 years of age. And once again, this is a 2:1 randomization, 2/3 receiving vaccine, 1/3 receiving placebo. Now, the primary effectiveness endpoint is different. So this was one that we negotiated with the FDA, and this is the basis for licensure. And what the regulators want us to show is that the immune response, the neutralizing immune response was non-inferior in the adolescent compared to young adults, 18 to 26 years of age. So if you achieve that endpoint then you achieve the data required for licensure. And it essentially says that the vaccine is meant to work as well in adolescents as it does in adults. However, we did look at efficacy used in the same definition as in the adults. However, because we could not be sure how many -- how much disease we would have in this group, the first effectiveness endpoint wasn't tied to the licensure-enabling endpoint. So let's move to Slide 5. Slide 5 depicts the strains that circulated during the time of the study. You can see the dose 1 and dose 2. [ One ] being starting in April 26, and the second dose 2 started going in on May 17. And we evaluated efficacy from May 24 to September 27, and you can see the diagram that Delta really predominated throughout that time period. This was before the rise of Omicron. So let's go to Slide 6 and Slide 6 describes the demographics of the population we enrolled. You can see it was split evenly by gender. We had more younger adolescents, 12 to 15 years of age versus 15 to 18 years of age. And this was likely because a vaccine became available for the older adolescents during that time, so there was less need for them to be recruited and enrolled. We did well as far as having both racial as well as ethnic diversity. And interestingly, the baselines are a positive rate. So those who came in prior to vaccination, 15% of them had already been exposed to COVID. Okay. Let's move to Slide 7, and Slide 7 describes the safety are at a very high level from [ what we saw ]. In this diagram, blue represents the vaccine group and gray placebo group. And you can see that any adverse events in the top bars are well balanced, [ if there were ] any medically attended adverse event. Severe disease, serious adverse events and deaths are at a very, very low rate and balanced between the 2 groups. In fact, there were no death. And I could say the majority of the SAEs were psychiatric diagnoses, probably showing the toll this Pandemic has taken on our children. Let's move to Slide 8. Slide 8 shows the local reactogenicity that we saw after the dose 1 and dose 2 of the vaccine. On the left-hand side, I'm displaying dose 1, and on the right-hand side, dose 2. And for each of the terms, pain, tenderness, redness and swelling, I broke those down by age groups. Now, what you can see by scanning the bars is really there wasn't any real difference between the age groups, the 12 to 15s versus the 15 to 18 as expected. We had a small increase in reactogenicity after dose 2. After dose 1, pretty much the adverse event, the reactogenicity events were similar to that in adults as well there are a higher grade event. After dose 2, they were generally similar, although we had a slight increase in redness and swelling in the adolescents compared to young adults, and we think that's just because their arms are thinner. So it's easier to spot that event. But the Grade 3 were similar to the adults. So now, let's turn to Slide 9, and Slide 9 shows the systemic reactogenicity event. The slide could have been sustained, dose 1 on the left, dose 2 on the right, with each category having both younger and older adolescents. And once again, you can see there's minimal difference between the younger and older adolescents. After dose 1, they were generally similar to those of young adults. However, there was slightly higher muscle pain. However, Grade 3 and higher were similar to adults. After dose 2, in general, they were lower than that seen in adults, except for headache, fever and nausea and vomiting. And once again, the higher grade fever or the higher grade events were the same as in young adults. Okay. Let's move to Slide 10. And Slide 10 is the licensure-enabling endpoint -- the effectiveness endpoint. So what we were asked to do here is to compare the neutralizing immune responses in young adults, aged 18 to 26 compared to the adolescent. And you can see in the main study, the 18- to 26-year olds had a geometric mean titer of 2,600 and the adolescents had a geometric mean titer of 3,800. So not only were they non-inferior, but in fact, they were superior, they were in a [ 4-fold ] higher than the young adults. And you can see the seroconversion rates were also quite high, 99%, more or less. On the bottom, I've marked down the GMT titers for [ neut ] is achieved in the Phase III study in the U.K. and the U.S. overall. And you can see these adolescents generated a neutralizing titer that was 3, almost 4-fold higher than we saw in the Phase III studies where we had good protection for both of those studies. So let's move to the next slide, which is another [ immunologic ] slide. This is looking at the magnitude of IgG. Once again, I've put the comparison on the right for your interest in the 18- to 26-year-old, they achieved a titer of 99,000. The children overall 139,000. And you can see the younger children had a higher magnitude of immune response compared to the older children. But once again, a favorable result for the children. Okay. Let's move to Slide 12. Slide 12 is data we've presented previously, and it's taking the serum from these children who received 2 doses and looking at the immune responses against a broad array of variants. And you can see for the prototype, we achieved titers above 100,000, and those are notching with Omicron providing the lowest result. But importantly, 100% of these children are converted to all the variants we tested in this assay. Now, we move to Slide 13. And Slide 13 is our hACE2 functional assay. So what this assay does is, it explores how well the antibody can block the variant spikes to the immunoreceptor. And importantly, in this assay, this is a very stringent assay. And in this case, these adolescents had a 2- to 4-fold higher response than in adult. So if you were to look over at the prototype bar, for instance, cut that in half, that is the response that was seen in adults that was associated with protection at the 90% to 100% range -- well, 100% for prototype, for alpha at 93% if you cut that in half. So that's the kind of response we're looking at and the meaning of that response perhaps. Okay. Let's move to Slide 14. Slide 14 is the clinical efficacy. This is depicting how much mild, moderate or severe disease that was in this group. You can see there were 6 cases in the vaccine group, 14 cases in the placebo group, and that results in a vaccine efficacy of roughly 80% with a lower bound of 46%. The lower bound met its statistical success criteria. And I have to say that, of these cases, 11 out of 20 were Delta, and all of our variants that we are able to sequence were Delta. In fact, all the sequences we were able to drive were Delta variant. Importantly, this is a small group, which is less than 10% of the overall adult study. So there's generally broad confidence intervals around this vaccine efficacy estimate. You can see, however, the 95% CIs overlap that we saw in a more precise adult study. So we think the adult study is a better reflection of how the vaccine performed, although it's clear that there were different variants in this study and circulated in the adult study. So, let's move to Slide 15, and this is an analysis looking at how the vaccine did in the younger adolescents versus older adolescents. And you can see the point estimates are very similar between 81% and 77%. And finally, let's look at Slide 16. Slide 16 is when we look at Delta specifically. So just those cases, we were able to confirm Delta variants. We saw 3 cases in the vaccine group, 8 cases in the placebo group, and that went to a vaccine efficacy of 82%, once again, with a lower bound above the required 30%. An important feature here, as well as with the overall vaccine efficacy is, all the cases were mild, and I'll comment on that on the next slide. But in general, vaccine efficacy is harder to demonstrate against mild disease versus moderate and severe disease. And that's just happened to be the way these adolescents became ill from the Delta [ when it hits them ]. So let's go to Slide 17. Slide 17 is the overall summary. There were no safety signals observed in this data set, which went through a crossover. The vaccines were well tolerated. The reactogenicity events were generally similar or of lower magnitude in severity compared to the young adults in the study, with those few exceptions I mentioned on that slide. Overall, the IgG and wild-type neutralization responses were higher than observed in adults, is where the IgG and hACE2-inhibition against the variants that we compare to the adult. We achieved our primary effectiveness endpoint, which demonstrated the neutralizing responses who are non-inferior to young adults. And in fact, the adolescent responses were about 1.5-fold higher than an adult. Our efficacy against Delta was 82%, with lower bound greater than 30%, and our overall efficacy was approximately 80% or around 46%. And this is whole criteria for success. And as I mentioned previously, these were all mild cases, which are generally more difficult to prevent with vaccination compared to moderate and severe cases. A small number of cases in this study, a very broad confidence intervals for the overlap [indiscernible] the adult vaccine efficacy of 90%. And finally, the findings were consistent between the 15- and 18-year olds and the 12- to 15-year olds. So let's move to Slide 18, just to give some next steps. We plan to start submitting this data to the global regulatory dossier in the first quarter of this year. We have Pediatric investigational plans agreed to by the FDA, MHRA and EMA. And the next study, which is an age de-escalation study and it's going to start in school-aged children. We're targeting that to begin early Q2. So with that, I'll hand this over to Silvia. Silvia?

Thank, Filip. Today, we see a continued need globally for a differentiated vaccine, specifically our protein-based vaccine, Nuvaxovid. We believe today's positive results demonstrate our vaccine' vast potential to protect against COVID-19 in pediatric population. With these data in hand, we remain focused on executing key next steps in our pediatric program, including filing globally to expand our authorization of our vaccine in the adolescent population and later to younger children. So with that, I now want to turn it over to the operator for Q&A.

[Operator Instructions] And our first question today will come from Georgi Yordanov with Cowen and Company.

And congratulations on the data. So just a couple on our end. On the SAEs that you saw in the adolescent child, do you see any [ aids ] related to myocarditis or anything similar to what we've seen with some of your competitors? And you alluded to some of them in the prepared remarks, but if you can just give us a little bit more color there? And then I do have a follow-up.

Sure. And maybe I'll even expand on the question you asked. So we did not see any myocarditis in this data set. In the larger data set that includes all of our studies, myocarditis happens sporadically, it happens in the placebo group and the control group at its usual rate. We do not have an imbalance in these findings. This has been adjudicated by the EMA, MHRA and all the regulators right now. And you're going to scrutinize the label, and you'll see that we don't have an adverse drug reaction of myocarditis in our labels. I'll have to warn you that we have a relatively small database. It's only 60,000 individuals right now. So as we deploy the vaccine in the broader population, we're keeping a very close eye on this and the other adverse events associated with vaccination. So we can make sure we inform the public and the regulators about how our vaccine performs from a safety perspective.

And the second question is around the Omicron variant. So just given that the Omicron variant has now become the dominant around the world, do you anticipate any difficulties in conducting a global pediatric study? And then related to that, do you have any updates for us on the Omicron-specific vaccine? And then given the results shown by some of your competitors, how do you see the need for a variant-specific vaccine at this stage of the pandemic?

Okay. There was a lot to unpack. And maybe I'll start, and Greg can jump in about the Omicron vaccine development. So, actually, I don't foresee a problem with enrolling children in the study. So first of all, Omicron in many places seems to be peaking and going down just from an attack rate perspective. I think we have good evidence that this vaccine induces a functional and a broad immune response, including against Omicron. Now, whether where we conduct the study, still has to be determined. It is likely to be a multinational study, and we hope to get a broad spread of children enrolled really throughout the world. Greg, do you want to talk about Omicron vaccine development?

Sure. So we are working on Omicron. I think we've got 2 strands of activity. One is to look at how our current Wuhan vaccine interacts with Omicron. As you may know, Filip showed some data today, and we have data on -- published data that's out there that show that there's very good cross reactivity with our Wuhan vaccine in Omicron virus protection. But we are also noting that there's quite a drop-off in many of the other technologies and over time, so that it suggested an Omicron vaccine switch may be needed in the future. So with that in mind, we have moved quickly. We are in GMP manufacturing, and we're expecting to start a trial of a vaccine candidate in the first quarter.

And I think your question is it needed? I think Greg answered that. It isn't clear. We think that the optimal product may benefit from being variant-specific. But we haven't actually seen a ton of data. I mean, I'd point you back to our own clinical data where we had that entire Greek alphabet variants that circulated and our efficacy was over 90% with complete protection against moderate and severe disease against those [ variants ].

And our next question will come from Charles Duncan with Cantor Fitzgerald.

And let me add my congratulations to the team on these data. I wanted to follow up on a previous question regarding myocarditis. And, I guess, yes, I appreciate your extensive answer to the last question, Filip. But, I guess, I'm wondering if there -- if you could speculate on any mechanistic rationale for Nuvaxovid for the vaccine being differentiated in terms of possible etiology of myocarditis. Is there any way to believe that this won't show up in an unbalanced way with your vaccine?

Yes. So I'm data-driven. And I think the data will show all, but I think you gave me the right to speculate. So we know the mechanism of some of the other adverse events of interest with vaccination, specifically thrombocytopenia with thrombosis. And this vaccine tend to do that, right? It can cause [ causing ] in the same way vis-a-vis adenovector can. The one thing I know about this vaccine is that, it works locally. So much of their immunologic action happens at the injection site in the draining lymph node, and that might be a clue for one thing, why we -- our systemic reactogenicity is slightly lower because all the action is kind of in those lymph nodes in brain from the injection site. And it may have implications for safety, we just simply don't know yet.

Okay. But you haven't seen anything thus far despite being over a year out from PREVENT-19 initial dosing, correct?

That's right. What I said was, I mean, we've seen cases in the vaccine group, we've seen cases in the placebo group. Our event rates are balanced and no regulator has [indiscernible] to adverse drug reaction to date.

Okay. And then with regard to the plan to submit this information to agencies for which filings are pending, would you anticipate this to be major amendment? And would it possibly change the kind of timing of an EUA review? Or are you -- and are you being prepared, getting prepared to file a full BLA if that's necessary as well here in the United States?

Okay. Also a relatively multi-factorial question. So we've already achieved regulatory approval in many territories. So in those territories, this becomes the first clinical variation, right? We already have the greater than 18, and this will bring in the 12- to 18-year-old. In the places where we still haven't been granted authorization, those applications have already been made. So they ought to have the full dossiers for greater than 18. So it's going to be a case-by-case basis with negotiation with those agencies to understand if they want to bring us into the initial EUA or if they want to do it sequentially, probably sequentially makes more sense, they can act faster. Now, that being said, it's up to them. And also remember, we can -- there are certain territories such as the U.S., where we can file the clinical study report directly into the IND. So they have access to this data even before they receive the official request for authorization, and [indiscernible] escalation.

Sorry, last question, subsequent pediatric study plan for Q2. Can you provide a little bit of color on its design and age range and size?

Yes. So, our preliminary plans us call for starting out in school-aged children, right? So 6- to 11-year olds before we age de-escalate to 2- to 5-year olds. You saw in our data that our immune responses were very high, higher in adolescents than in adults. And perhaps you saw in a couple of those reactor events, specifically the tenderness/pain and some of the vomiting and so forth, it was creeping up in that group as well. We think we have a very safe product that has low reactogenicity. I want to remind you that this adjuvant has been used -- is being used in a Phase III malaria vaccine study that's ongoing in Western Africa. And they've taken this down to children as low as 5-month of age, and not had a problem. So whether we choose to do fractional dosing at some point in the children, will really be in conjunction with discussions with the DSMB and with the regulators. But right now, we're aiming to try to take our full dose into kids as young as is tolerable and is required.

And congrats on the update.

And our next question will come from Eric Joseph with JPMorgan.

So just a couple from us. With all the [indiscernible] cross-file comparisons, I'm wondering, Filip, whether you venture a comment as to how these efficacy data in adolescents compare with either the mRNA vaccine. I know there's different time periods and regions in which studies are being conducted, but maybe just at this point, would you kind of comment on whether this efficacy might support differentiation in protection compared to mRNAs? And then, secondly, regarding the regulatory process here in the U.S., just wondering if you might comment on when you would get the confirmation on the eligibility of -- [ is actually ] for EUA having sought a request for that?

Yes. So you're a little bit hard to hear, but I think your second question was, when do we think we're going to get our EUA in the U.S.? And we're in the middle of the regulatory process, and I don't think we have a clean visibility into that. Silvia, do you have anything else to say on that topic?

You're right.

Okay. And the first question you were asking for me to make a comparison between this data and other sponsors adolescent data. And I'm not sure I can do that. I think the difficulty is equivalent to that are true, people use different case definitions. And certainly, the epidemic has changed in children, depending on the variant, et cetera. So without a head-to-head study, I'm not sure that's possible. What I can tell you is that, we're quite pleased with this data, and we're confident that we're seeing another data point showing we have consistent efficacy against variant, as well as non-variant. And our product is well tolerated. So we think it has a bright future.

And our next question will come from Mayank Mamtani with B. Riley FBR.

Congrats on these results. So maybe the first question is around, anything incremental from this data set we gleaned on the durability of protection, be it from VE numbers or immunogenicity data? Looks like everything is in that short time period follow-up. Just wanted to confirm with you if there's anything about durability that we could learn from this data set.

Yes. That's a good question, and you're right. This have a crossover design. We have to do that to main study integrity as with our other studies. So the efficacy you saw was really in a relatively short amount of time that happened between primary vaccination and the crossover. As far as what you can try to drive from this data as far as the durability from an immunogenicity perspective, one feature is that, these adolescents. The levels were high, they were 2 to 4x higher in adults. So we know that the antibodies decay at a pretty [ depictable ] rate. So you could expect perhaps there may be some longevity of protection in adolescents compared to adults. But since we don't have a great estimate of longevity in adults yet, I'm not sure that was very helpful.

Got it. And then on the safety reactogenicity specifically systemic, I appreciate the color between adults and this population. I was just curious if you could talk what the placebo rates were for some of these events that you broke out specifically for Grade 3. Like just want to understand if there's any implication of that?

Yes, that's a good idea. I didn't bring that data. We'll see if we can make that available to the community.

And my final question was about the pediatric studies that might be ongoing in certain territories where you might be going as low as 2 years old or your partner might. So, can you give us a status on what those studies are and when we should expect data from that?

Yes. I think you need to talk to -- I believe you're referring to a study which is ongoing in India by our partner, Serum Institute. They are doing a pediatric study where they are age de-escalating down to 2 years of age. You would need to ask them about details about those studies since they are the regulatory sponsors. We think it's going to be supportive to this data we generated here today, but the efficacy data will be coming from this study and not from the study that they're conducting.

And this will conclude our question-and-answer session. I'd like to turn the conference back over to Silvia Taylor for any closing remarks.

Thank you, and thank you to all of you for joining today's call. We're excited by our results discussed today, and we look forward to reporting on additional milestones in the months to come. Have a good evening.

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect your lines at this time.