Novavax Inc (NVAX) 2021 Q2 法說會逐字稿

Good day, everyone, and welcome to the Novavax Second Quarter 2021 Financial and Operating Results. (Operator Instructions) Please note that this event is being recorded.

I'd now like to turn the conference over to Silvia Taylor, Senior Vice President, Corporate Affairs and Investor Relations. Please go ahead.

Thanks, Cole. Good afternoon, everyone, and thank you to all of you who have joined today's call to discuss our second quarter 2021 operational highlights and financial results. 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. We've also posted the slides we are using during today's call under Events in the Investors section of our website.

Joining me today is Stan Erck, President and CEO, who will provide an overview of our progress in the second quarter, our supply commitments, our regulatory time lines as well as updates on manufacturing; Dr. Filip Dubovsky, Chief Medical Officer, will discuss developments for our COVID-19 program; and John Trizzino, Chief Commercial Officer, Chief Business Officer and Interim Chief Financial Officer, will provide an update on our financial results for the quarter. Additionally, Dr. Greg Glenn, President of R&D, will be available for the Q&A section at the end of today's call.

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 projections 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 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 would now like to hand the call over to Stan. For those of you following the accompanying slides, please turn to Slide 3.

And thank you, Silvia, and thanks to everyone for joining us today. As we start this presentation today, we can note that through the development of vaccines and treatments to date, significant progress has been made to combat the COVID-19 pandemic. However, we also note that with the continued circulation of variants and with the inequitable access to vaccines that persists in many parts of the world, Novavax' mission to bring NVX-CoV2373, to market as swiftly as possible has never been more important.

At Novavax, this week, we took a major step forward in advancing this mission. We are announcing the filing of multiple regulatory submissions for 2373 with our partner, Serum Institute. These regulatory submissions encompass global markets, including filings with the Drug's Controller General of India as well as with regulatory agencies in Indonesia and the Philippines. We view these submissions as the first of many, bringing us 1 step closer to delivering 2373 to those in need.

In addition to these regulatory developments, I'd like to begin today's call by providing an overview of a few of our major achievements in all areas of our business since the beginning of the second quarter. We announced positive data from our PREVENT-19 pivotal Phase III trial, demonstrating 90% overall efficacy and 100% protection against moderate and severe disease. Filip will talk more about this shortly.

We took major steps in exploring 2373's boosting capabilities, including positive results announced today from our 6-month booster study in our ongoing U.S. and Australia Phase II trial. In conjunction with our PREVENT-19 trial, these outstanding data make a compelling case for 2373 to become the universal booster of choice.

We also continue to explore heterologous boosting alongside other vaccines in the market by participating in 2 partner-led studies: the Com-COV2 study and the CoV-Boost mix-and-match study being conducted in U.K. We furthered the global reach of our vaccine candidate, finalizing advanced purchase agreements with Gavi for 1.1 billion doses and with the European Commission announced yesterday, for up to 200 million doses of 2373.

And on the manufacturing front, we continue to work closely with our global partners to progress toward our anticipated manufacturing capacity. We have made significant progress during the quarter to ready our global supply chain for the delivery of 2373 following anticipated regulatory approvals. And today, we reaffirm our guidance to be at a monthly capacity of 100 million doses by the end of the third quarter and 150 million doses by the end of the fourth quarter.

In parallel with these developments, we have our eye on the future, advancing other candidates in our pipeline that we believe are pivotal in our ability to continuously address the world's most urgent global health needs. We are excited to share with you more about these and our many other achievements in the second quarter.

Today, our management team will discuss clinical developments for 2373 and our financial results for the second quarter. And I will discuss updates on our supply commitments globally, progress toward regulatory approvals of 2373 and the status of our manufacturing and global supply chain. I'll also highlight our key areas of focus moving into the remainder of 2021 as well as 2022 and beyond.

With that, I would now like to hand the call over to Filip to discuss our many clinical developments over the second quarter.

Thanks, Stan. We achieved a number of milestones in the second quarter across the clinical program, and I'll highlight a few of these in the overall context of our studies.

So maybe switch to Slide 5, please. So here are the clinical programs that we've conducted over -- been in the development. We started off in the Phase I, Phase II in the U.S. Australia. There we established the dose level, the hemologic profile and the preliminary safety profile of the study, and this is a study that's ongoing, and we've conducted some 6-month boosting, which I'll talk about later.

Moved on to a Phase II study in South Africa, and this is our preliminary efficacy evaluation as well as defining the overall safety profile and exploring the efficacy and safety in a small group of HIV subjects. Moved on to our first big Phase III study in the U.K., and this is a licensure-enabling study that collected licensure-enabling safety as well as efficacy data, included a small influenza co-administration study, and I'll touch base on that data a bit later as well. And finally, we conducted a large Phase III study in the U.S. and this define the safety data and immunogenicity data as well as efficacy there in the U.S. population.

Let's move on to Slide 5, please. We just want to remind you of the design of the PREVENT-19 study in the U.S. and Mexico. And this is a study that included 30,000 adults age greater than 18 years of age, and it was randomized 2 to 1. And as you know, we've gone ahead and crossed these people over in a blinded crossover fashion, and the enrollment in the 2 dose crossover is almost complete.

Additionally, we expanded this study to include adolescents, 12 to 18 years of age, and we enrolled 2,248 of these children. The dosing is complete and the file for safety, immunogenicity and efficacy is ongoing. We have a blinded crossover planned, and we should be beginning that next week.

So let's move on to Slide 6, please. Here, what I've displayed is the Kaplan-Meier curve for the primary efficacy end point. And overall, as you remember, the overall efficacy was 90%, as Stan mentioned. From this graph, you can see a couple of other things. You can see the separation of the vaccine of placebo rates began before day 21, before the second dose was given. Additionally, you can see through day 90, there's no convergence of the rights suggesting durability of protection for our vaccine. And finally, I want to remind you that all the severe cases occurred in the placebo group.

So let's move on to Slide 7. Slide 7 contains data, which is updated from we chatted last and this is because we got additional sequence data from the disease cases in the study. So the way this slide is designed is that the variance of concern are in red, the variance of interest are yellow in the variants that are neither of concern or interest, those that represent the strains closest to the Wuhan strain, more like matched strains are represented in green.

You can see the overall, we had 14 cases in the vaccine group and 63 cases in the placebo group. And I remind you, this was a 2:1 randomized study. So you can consider the placebo group, half of where we have normally been in the 1:1 randomized study. And that efficacy like we talked about was 90% with a lower bound of 83%.

Our key secondary endpoint was against strains that were neither variants of interest or variants of concern. That was most like the Wuhan strain. And there we had 100% efficacy. You can see there are no disease causing strains in green under the vaccine column. Against moderate and severe disease, we had 100% efficacy with a lower bound of 87% and that's irrespective of variants or nonvariants. You can see there were no cases at all in a moderate disease group under the vaccine column. And finally, we had exploratory analysis against variants of concern and interest, which we saw efficacy of 92.6%, with a lower bound of 80%.

We had enough cases in this study also to estimate the vaccine efficacy against B.1.1.7, which is the alpha variant first seen in the U.K. And there, we had a point estimate of 93% with a lower bound of 80%. What's remarkable across all of these end points is really the consistency of the efficacy as well as the precision and the high lower bound.

So let's turn to Slide 8. Slide 8 outlines the design of the U.K. study. This is a 1:1 randomized study with 15,000 adults greater than 18 years of age. And this also we crossed the subjects over and enrollment of all the crossover vaccinations has been complete.

So let's move on to Slide 9, which shows a Kaplan-Meier curve of the primary endpoint. As we've talked about previously and it's published now, the primary efficacy was 89% overall. Once again, you can see the separation of the curves beginning right at day 21 or before. And once again, there's no convergence of the curve suggesting durability of protection. There is small red S' that denote severe disease, and they're all in the placebo group. In fact, over all of our programs, we have yet to see a severe case in the vaccinated group.

Let's turn to Slide 10. Part of this study was a influenza substudy where people received a licensed dose of influenza vaccine with the first dose of 2373. What I've highlighted here is the local and systemic reactors and events. Left-hand side is local of both placebo, flu alone, Novavax alone and then a carbonation Novavax and flu. And what you can see is that the efficacy profile is quite favorable. There's a small increase in the amount of mild symptoms, but overall, the vaccine is tolerable. And this is mimicked in the systemic side as well.

The influenza HAIs and seroconversion were preserved with coadministration, and I'll detail this data in a subsequent slide. And I'll remind you that the overall efficacy of the study was 89.7%. And when we did a subgroup analysis of those in the flu study, we saw that the efficacy was preserved at 87.5% even though there was a very small subgroup of only 400 individuals.

So let's go to Slide 11 and look at immuno. So as displayed on Slide 11 is the HAI responses of people who received the license vaccine alone compared to when given with 2373. On the left-hand side, you can see the quadrivalent data, and this is people who were aged 16 to 64 years of age who by standards in the U.K. received quadrivalent cell culture influenza vaccine.

The older subjects received adjuvanted vaccine and they're on the right-hand panel. This was a very small group of older subjects because the public health infrastructure in the U.K. works very well. And we only had 16 subjects who received our vaccine plus influenza, so the confidence intervals are quite wide.

However, on the left-hand side, these were a larger group of individuals, so we can be more precise in our estimates of the immune response to the flu vaccine. And you can see that the HAI responses to flu vaccine were preserved for all 4 strains. In fact, numerically, the HAI responses as well as seroconversion responses were higher in the co-administrated vaccine compared to the vaccine alone.

So let's move on the next slide, Slide 12, please. This is a comparison of the efficacy results from our 2 Phase III studies that were independently conducted and powered. You can see that the efficacy was remarkably consistent 89% in the U.K. study and 90% in the U.S. study, less than a single percentage point difference in the 2 studies indicating that the vaccine response is very robust.

Against matched strain efficacy, in the U.K., we saw a 96% against the prototype. And in the U.S., Mexico, where we had greater variant spreading, we saw 100% efficacy against those who were not variants of concern or interest. Again, efficacy against variants in the U.K. was 86% against alpha, in the U.S., 93% against alpha, and overall, in the U.S., variance of concern and interest 92%. So this vaccine works quite well against variance impact.

And finally, we have this observation that in the U.S., our efficacy in severe disease was 100%. We didn't have enough cases in the U.K. to estimate efficacy, but all severe cases were in the placebo group. And I would say also in the South Africa, all the severe and hospitalized cases were in the placebo group as well.

So let's move on to Slide 13, please. Slide 13 is a display of the South Africa Phase IIb design. And the only point I want to make here is that enrollment of all the crossover and boost vaccinations has started. And this design is a little bit different from the other 2 in that the people who received placebo initially got 2 doses of vaccine at 6 months. However, the people who got 2 doses initially got a single boost dose at 6 months. And this will allow us to collect additional boost data, both from a safety and immunogenicity perspective in this population.

So let's move to Slide 14, please. Slide 14 despites the study design of our Phase IIb study that we started in the U.S. and Australia over a year ago. Here, we enrolled 1,208 adults aged 18 to 84, and half of those were adults who are greater than 60 years of age. After the 2-dose primary series, we went back and we boosted some of these select individuals at 6 months of -- to 6 months.

We plan an additional boost at 1 year. And the groups that I've highlighted in red -- perhaps click, please. They are highlighted in red and on the printed slides are the group will be talking about. These are people who received 2 doses initially at day 0 and 21, and half of them were boosted at day 189 with a 5-microgram dose of 2373.

Let's go to Slide 15, please. So Slide 15 displays adverse events comparing dose 1 to dose 2 to dose 3. And we've displayed adverse events overall, severe adverse events, medically attended adverse events, SAEs, discontinuations and a potentially immune-mediated medical complications. And you can see there's a lot of consistency between dose 1, 2 and 3, and there is an excess of adverse events in dose 3. And the rates of severe AEs and SAEs are very low indeed. So this data was reviewed by our external safety motoring committee, and they voiced no concerns and suggest that we proceed with vaccination.

Let's move to Slide 16, please. Slide 16 highlights the local systemic reactions after vaccination. And what you can see is for the local reactions, we had an increase of (inaudible) for dose 2 and then additionally for dose 3, which is completely expected with additional vaccinations. What you can also see is that more than 90% of the reactions were either none, mild or moderate with a very low rate of grade 3 or more events. The median duration was short, less than 2 days median, with the exception of erythema, which was 2.5 days.

Let's go to Slide 17, please. Slide 17 is the companion slide, which details the systemic symptoms, and it's very similar to what we saw previously. As expected, the symptoms increased with dosing. And with the exception of fatigue, more than 90% reported either none, mild or moderate symptoms, and the event rate was quite low overall. Once again, the median duration was short, less than 1 day with the exception of muscle pain, which is 2 days.

Let's move to Slide 18 and look at some immuno data. What I've detailed here is the immune response, the immunokinetics of anti-IgG response conducted with our validated assay, and this is against a prototype. So you can see the peak response after 2 doses on day 35 was 41,000, which decreased over time. When we boosted it, it rose up to over 200,000 units. And this represents a 4.6-fold increase compared to the peak seen after primary vaccination.

Go to Slide 19, please. This is the same data, but it's displayed by age. And the point here is that in both younger and the older adults, we had a good impact from boosting. In fact, the impact to older adults was even higher than younger adults to the boost, which is likely because they have slightly lower titers to begin with.

Let's move on to Slide 20, please. So all the data I've shown you up until now from an immunogenicity perspective, was against our validated anti-spike for the prototype strain. We also developed a validated anti-spike assay for the beta variant, so the 1 was first identified in South Africa. And you can see we got a really nice boost with that as well. From a 4,400 a day at the 6-month time period to over almost 170,000 a day 217. So what we have here is some evidence that the vaccine has potential to cross react against variants. know this is true because we have good efficacy against variants.

Let's go to Slide 11, please. Slide 21 displays wild-type neutralization. Once again, this is against the prototype strain. And you can see very similar patterns to what we saw with the IgG responses at peak day 35, midyear at month 6 and boosted to over 6,000 with an increased fold rise in the older adults.

Let's move on to Slide 22. So on this slide, what I've displayed is the peak responses that we observed in the U.K. Phase III study. Next to that, in the middle column is in the immune responses that we observed in the PREVENT-19 study. And finally, on the right-hand side, I have the boost data we just showed. Additionally, I've put in the vaccine efficacy as the top of the Phase III studies. And what you can see is that compared to the 2 Phase III programs, where we showed efficacy, not only against variants, but also against non-variants we had a 4.7 to 4.4 fold rise. This gives us a lot of hope that we're going to increase durability of protection as well as protection overall.

Let's move on to the next slide. This slide is a companion slide which shows wild-type microneutralization responses. And once again, you can see the peak responses in the U.K. as well as the U.S. Phase III study and that we had a large boost from these with our -- in our Phase II program.

I guess a couple things to point out here. One of them is that the fold rise is greater for the microneutralization than for IgG. And this suggests the potential maturation of immune response with greater spread. I'll show you a little bit more data about this in the next couple slides. We were quite curious to understand our immune response to these vaccines -- to this vaccine because we had such good efficacy against the variants.

Let's move to Slide 24. Slide 24 is a pretty complicated slide, so I'm going to take my time going through this data. We developed a functional human ACE2 inhibition assay. So what we did is we developed spike proteins from the prototype strain, delta, beta and alpha. And what we do in this assay is we show that antibodies that are generated by vaccination can block that interaction. So this is a functional assay.

On the left-hand side, you can see the day 35 data. So the day 35 data is the peak response after 2 doses. And in black, you can see the prototype; in blue you can delta; in red, beta; and in green, alpha. And I want to remind you that the efficacy against the prototype was between 96% and 100% and against alpha was between 86% and 94%. And the other variants displayed functional immune responses that lie between those 2. So we have high hope that the efficacy against those variants will be somewhere between that, which we saw for the prototype and that which we saw for alpha.

On the right-hand side, you can see the responses after boosting, and we had between a sixfold to 10.8-fold increase over what we saw at day 35. Importantly, Delta is getting a lot of attention. You can see that it had a 6.6-fold rise over the peak response after the primary vaccination series.

Another couple of observations on this part of the graph. One of them is that we left no one behind. You can see that 100% of the people were boosted into high levels, especially when you compare the levels we've seen here to those which were shown to be protected on the left-hand side of the graph. Another observation is that we really have very consistent responses across the 3 variants, and this we attribute really to the maturation of the immune response with boosting.

So let me move on to Slide 25, which is a quick clinical summary. So we have data from 2 independent Phase III studies that have shown high levels of vaccine efficacy: in the U.K., 89.7% overall; in the U.S. over 90%. And both of these studies have shown strong efficacy against variants, against both the B.1.1.7, the alpha variant as well as all variants of concern and interest in the U.S. study.

Next slide. I've shared with you today about our single-dose boosting at 6 months and this significantly increases immune responses. Both wild-type neutralization as well as anti-spike IgG were boosted between 4.3 to 6.4-fold over the peak primary vaccination response. In our functional hACE-2 immune response, we were able to take this against alpha, beta and delta, not only in our primary vaccination series, but also after we boosted it and these went from a peak of 6.6- to 10.8-fold increase. We think that this data will support the use of our vaccine in a boosting campaign.

And furthermore, we shared data with you that the co-administration with flu doesn't adversely impact the influenza immune response. So we have high hopes that our boosting could be incorporated into the annual influenza vaccination campaign.

So let me turn this back over to Stan.

Thanks, Filip. Moving to Slide 27, we provide an overview of our supply commitments to date. There remains significant demand for 2373 globally with vaccination rates varying widely from country to country. We continue to see significant opportunity in ex U.S. markets to provide supply for initial vaccinations. In high-income countries, we believe our technology well positions us to become the booster of choice.

Yesterday, we were pleased to announce the finalization of an advanced purchase agreement with the European Commission for the purchase of up to 200 million doses of 2373. We expect to begin delivery of initial doses following anticipated regulatory approval from the European Medicines Agency. And through this agreement, 2373 is expected to be the first protein-based COVID-19 vaccine available in the European Union.

Additionally, we finalized our APA with Gavi reaffirming our commitment to fair and equitable access to 2373, the cumulative 1.1 billion doses that we, alongside our partner, Serum Institute Committed to the COVAX Facility will be critical in ensuring widespread initial vaccination, particularly in developing markets.

So let's turn to our regulatory and manufacturing updates. I'm excited to discuss our progress during the second quarter for 2 key areas: the first is our progress toward de regulatory authorization of 2373 and anticipated time lines for completing our filings; the second is our progress towards achieving our anticipated manufacturing capacity and our expectations for the supply of 2373 globally. I will then discuss our key areas of strategic focus for the remainder of 2021 as well as our expectations moving into 2022 and beyond.

Starting with our efforts to gain regulatory authorization 2373 this week, by submitting its first regulatory filings in multiple countries, Novavax has graduated to a new level.

Please turn to Slide 28. As I mentioned earlier on today's call, we filed regulatory submissions in multiple markets in partnership with Serum Institute. These regulatory submissions for emergency use authorization were filed with the Drugs Controller General of India and regulatory agencies in Indonesia and the Philippines.

We expect to file for emergency use listing to the World Health Organization in August. We expect that the granting of emergency use listing by the WHO will open the door for exports to numerous countries, many of whom are participating in the COVAX Facility. These major milestones reflect the strength of our continued partnership with Serum Institute and mark an important first step toward accelerating global equitable access to 2373. We expect these submissions to be the first of many with additional filings expected in the coming months.

We are also working on submissions that will eventually cover the rest of the world because we're dealing with regulatory agencies that have different requirements and in countries that have different needs, these regulatory filings and the subsequent approval processes will occur over a series of months. Let me cover the ones that we are working on now.

In the U.S., we are continuing to work with the FDA in collaboration with our team that we now refer to as the U.S. government to finalize our filing package for authorization under emergency use authorization. The current time line looks to now be in the fourth quarter, hopefully early in the fourth quarter. This time line is based upon a couple of factors. First, the completion of validation of analytical methods. And additionally, we have many complex critical activities as part of our finalization of our authorization submission that are being carried out with multiple third parties. Importantly, I believe all the key components are in place to achieve our filing within the fourth quarter.

The good news is that the EUA pathway remains open. Peter Marks, Director of the Center for Biologics Evaluation and Research at the Food and Drug Administration was quoted in a Bloomberg interview this week saying that, "There probably is going to be a point at which we stopped giving emergency use authorizations. But right now, one wouldn't want to rule out continuing to give emergency use authorizations." We still don't have an approved protein-based vaccine, for instance, and there are some people here that might be a very good alternative. So I think that's good news.

So regarding our progress toward completing regulatory filings in other geographies, we continue to advance our program with the MHRA, which is the U.K. regulatory agency, we are targeting to submit to MHRA in the third quarter, but as with all applications, this may change based on discussions planned for later this month to support our planned application in the third quarter. Given that there are many countries who will rely on MHRA authorizations as a basis for their own regulatory approvals, this is another important global filing.

In addition to filing with the MHRA, we are preparing to file an additional important markets within weeks of the MHRA filing, including the European Medicines Agency, the Australian Therapeutic Goods Administration, in Health Canada and in New Zealand through MedSafe. As always, gaining regulatory authorization for 2373 remains a top priority as we move into the remainder of 2021, and we continue to work tirelessly with regulatory authorities to complete our filings. We view the completion of multiple filings announced today as a significant first step but only the first step in gaining authorization of 2373 around the world.

So moving to Slide 29. Next, I will discuss our anticipated time line towards achieving our manufacturing capacity and progress made during the quarter to prepare our global supply chain for commercialization. Today, we remain on track to achieve manufacturing capacity of 100 million doses per month by the end of the third quarter of '21 and 150 million doses per month by the end of the fourth quarter of '21. Our manufacturing and developments during the second quarter reflected our progress toward reaching our anticipated manufacturing capacity as well as our efforts to proactively build our -- for future expansion.

Notably, we took additional strides towards producing 2373 in Canada, initiated technology transfer to produce 2373 at the National Research Council's Biologics Manufacturing Center in Canada. We're excited to see such progress at this facility, which completed construction in June '21. We expect to begin large-scale GMP manufacturing once the facility receives regulatory approval from Health Canada. The production of 2373 in Canada will represent the first manufacturing capacities in the country for a COVID-19 vaccine.

We expect our global supply chain to support expansion of distribution 2373 beginning in the second half of '21, and we anticipate shipping vaccine upon anticipated regulatory approvals. Initially, our doses may be prioritized to low-income countries where we'll be able to support critical unmet demand for primary vaccinations. We view our partnership with Serum Institute as a key component in delivery supply to low and middle income countries, including Serum Institute's contribution to the COVAX Facility.

We remain confident in our ability to deliver upon our bilateral supply agreements, including with the European Commission as well as our commitment to the U.S. government, especially as the need for boosters increase among high-income countries around the world.

With that, I'd now like to hand over the call to John to discuss our financial results for the quarter.

Thanks, Stan. Moving to Slide 30. We issued our second quarter earnings press release, which discusses our financial results for the quarter, and we'll be filing our 10-Q for the second quarter 2021 today, which includes details on important business and financing events during the second quarter. With that said, I'd like to provide a high-level overview of some of our key financial results for the quarter.

Novavax's revenue in the second quarter 2021 was $298 million compared to $36 million in the same period in 2020. This increase was due to increased development activities related to CoV2373 under the U.S. government and CEPI agreements.

During the quarter, we filed an ATM offering in June 2021, which allowed us to issue and sell up to $500 million in gross proceeds of common stock. As of June 30, 2021, no shares have been issued under the new ATM. We ended the quarter with a strong cash position of $2.1 billion compared to $806 million at year-end 2020. This increase in cash was primarily due to $1.1 billion in payments received under advanced purchase agreements, the timing of payments to third parties, and the $565 million of ATM funding in Q1.

With that, I would now like to turn the call back to Stan to discuss our strategic focus for the months to come.

Thanks, John. Turning to Slide 31. I will lastly highlight our key areas of strategic focus for the remainder of '21. These include the following: completing additional regulatory filings and gaining regulatory authorizations of 2373 in multiple markets; readying our global supply chain for commercialization and reaching our anticipated manufacturing capacity of 150 million doses per month; beginning expansive distribution of 2373; and finally, advancing life cycle management of 2373.

We believe these near-term priorities are critical in laying the foundation for commercial success in the coming years. As we look towards 2022 and beyond, we believe that the clinical development of 2373 to date positions our vaccine to become the universal boost of choice and the preferred vaccine for annual revaccination.

Our differentiated technology as well as our global chain will enable us to support demand in an anticipated booster market in 2022 and beyond. As we continue to develop other areas of our pipeline, both our variant strain and combination vaccine programs will play a meaningful role in our long-term success, enabling us to effectively address continued evolution of COVID-19 alongside seasonal influenza.

Before opening the call to Q&A, I wanted to take a moment to acknowledge and thank the Novavax clinical trial participants around the world. These individuals made a crucial and life-saving contribution during an unprecedented global pandemic. And now they are the reasons that some countries are starting to reopen. I and my colleagues have heard from many of you about your experiences, and we are grateful for your generosity.

We know that in some situations, clinical trial participants are being challenged with respect to proof of vaccination. We want these folks to know that we are doing everything we can to advocate for them. This includes working with governments to make the case that those who participate in clinical trials should be considered fully vaccinated from a public health perspective and treated in the same manner as someone who has received a deployed vaccine. These are unprecedented questions, and we are supporting the efforts to devise solutions.

While we can't control the decisions that countries and private entities make around vaccine mandates, we will also do our best to keep you informed on our progress. I want to reiterate that we are working day and night to finalize the requirements for the submission process, and I want to personally thank all of the clinical trial participants for their vital contributions to public health during the pandemic. For those who have reached out to us directly, we appreciate you willingness to know about your situation.

I'd also like to thank our entire Novavax team for their continued dedication an over incredibly busy quarter. These tireless efforts, combined with the support of our partners globally, bring us significantly closer to delivering our COVID-19 vaccine.

And I would now like to turn it over to the operator for Q&A.

(Operator Instructions) Our first question today will come from Kelechi Chikere with Jefferies.

Congrats on all the progress you've made over the quarter, and thank you for the comprehensive update. I guess on my first question, what gives you confidence that you'll be able to file in the U.S., EU and U.K.? And I guess how much risk is there associated with addressing some of those last remaining issues that are the gating steps to those filings? Any color there would be extremely helpful.

Yes. I think the risk reduction is dramatic. I think that it's a matter of now mechanics of getting all the data -- final data assembled and submitted. And it's -- we're talking weeks here. We're not talking months. So I'm not worried about the future submissions.

Got it. So you believe that at least the time lines that you've put forth, you'll be able to reach those. Is that more or less correct?

I do. This is a very big transformation -- transition of the company we filed. We've now filed with the regulatory agencies in 3 countries, and we've got a complete filing package for those we are finishing the additional requirements in the various countries that I mentioned. We've listed dates that we plan on making with a lot of confidence.

Got it. Got it. Perfect. And I guess my last question, what additional data do you need to generate and -- to file to support your booster strategy campaign? Does it make sense to -- is there even a possibility that you can include some of the data that we're seeing here in the EUA filings to the U.S., EU and U.K.?

Yes. So certainly, we've shared this data with some of those agencies informally. I think initially, we were planning to file with just the overall primary indication of better than (inaudible) of age for the primary vaccination. And this data will follow on for a subsequent variation. Hopefully, this data will be in even prior to beneficial BLA or MAA. I think we've done very good.

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

Congrats on progress being made here. So if I may just ask a quick follow-up on the U.K. filing that seems to be taking a little longer than maybe that was anticipated. I'm just curious if the Com-COV2 data that is being worked upon also a mix-and-match vaccine data. I'm just curious if you have an update on that. And if that data set is playing any role with what is going on in the U.K.? And if you can comment on the CMC side, the first part of that question would be helpful, too.

Okay. Well, I'll take the clinical study portion of the question. So there are 2 studies that are being funded by the BTF and are being done by University of Oxford in Southampton. One of them is a heterologous vaccination study that you referenced, Com-COV2. And the other 1 is a boosting study where people receive 2 doses of other response vaccines that are being boosted by our vaccine, and that's the CoV-Boost study. Those data -- those studies are sponsored by ourselves or sponsored by the universities. And we understand the data will be very valuable and published in the September time frame, so look forward to that data as with yourselves.

We've discussed this data with the U.K. regulators and they suggested it would be helpful, but I thought that our Phase to boost data in conjunction with our South Africa data, would really be desirable to include it in a labeled indication.

Great. And maybe if I could ask a specific question on the boost data here. The headline number of 4x on both IgG spike and also the wild-type utilization, how do you see this compare relative to maybe what we have seen with mRNA? And then the IgG decay here in your kinetic seems quite steep. I'm just curious, Filip, how should we think about that? Is there anything with the platform? Or just we should be expecting this sort of decay at 6 months irrespective of mRNA or a protein-based vaccine?

I guess a couple of thoughts, and Greg can jump in as well. I'm not sure that measuring the absolute value of either (inaudible) or IgG at 6 months is an indication of efficacy at that time point. I think we've seen that from some of the other sponsors who started before we did and have data in that regard.

We certainly haven't seen any decay in the Kaplan-Meier curves that I showed you, although clearly, that was only for the first 90, 100 days or so. I guess the other thing is that assays matter in different kind of assays measure different things. And finally, I would say it's not only the quantity of the antibody we induce but also the quality. And you saw from the data we showed was a functional H2 inhibition results that our antibody is able to really cross neutralize variants. Probably cross neutralize isn't the right word, to be able to block the functional interaction between Spike in ACE2.

So much like we saw with the influenza study, where we had good cross protection against drifted strains. I think we're seeing the same thing. This is a combination of the absolute titers you achieved and how good your antibody levels are. And I guess the other point is that these titers, if we hit titers of 200,000 like we demonstrated here, that's going to take a very long time for that to decay, and we have a much better chance of spreading in binding and protection because of the boost data and the maturation of immune response. Greg, do you want to say anything?

That's good. Thank you.

Awesome. And my final question on manufacturing, maybe Stan, are you able to comment on sort of what might be your monthly run rate, say, for July or anything on the doses that you may have stockpiled or even like the shelf life because I think folks are concerned that this bureaucracy of getting -- just getting into the market might be impacting what doses you may have already sitting on the shelf and not getting to people who can benefit from that?

Yes. I think we're certainly working to make sure that we don't run into a shelf life problem of product being made. We have been successful in extending dating from 6 months to 9 months on a variety of our in-process work. Our expectation is that's not going to be an issue. We expect a fairly rapid licensure, and we expect to be able to use the product we make -- that we're scaling up right now.

We're scaling up globally to this rate of 100 million doses by the end of next month. And so you can figure out what that rate is to get to that point and then from 100 million to 150 million. But our -- until the product is filled, we don't have to worry about dating because the drug substance, the antigen itself is frozen. So that's all on the shelf. We've got many tens of millions of doses they're already ready to go. And by the end of August when we expect to begin shipping, being able to ship, we'll have -- globally will have probably over 100 million doses that we're able to ship. So we're work cooking on that issue. I mean it's going well.

Our next question will come from Charles Duncan with Cantor Fitzgerald.

I had kind of a broader question to start with, and that is regarding an annual boosting campaign. I guess I'm wondering if you could lay out how you think that would look and what you think the strongest source of competitive advantages that you may have? Is it in distribution? Or is it efficacy or tolerability or an ability for your vaccine to work nicely in the sandbox, if you will, with other vaccines such as influenza?

Well, maybe I could add to that from the medical side. And like Stan said, pretty much all of the above. I think that we'll see as additional data emerges what the exact reaction profile of various vaccines are when they're given either a homologous boosting or heterologous boosting. And I think we'll have an advantage there. I think we've demonstrated that when we boost with our vaccine, we get very broad protection against all the brands we've tested it against. To be clear, I mean broadly immune response against all the variants you've tested against. So I think we're in good shape there as well. I suspect that as we go forward, we're going to have additional data, which is going to speak to the pathology of our vaccine and how long we can use it in the shelf life and so forth.

Yes. I would just add, Charles, that there's a variety of factors here. And I think you heard in the presentation and the data that was presented today, that we're confident in the benefit and value of our boost strategy. But it really remains some additional data to be collected globally on what that policy position -- our global health policy position is going to be on Boost and what the time frame is for that.

So we're obviously collecting all the information relative to the data we had -- we're looking at the data from the other manufacturers. And certainly, we're in communication in the U.S. and globally about what that health care policy will be to support a boost strategy. And I think the data is suggesting that we're prepared for whatever that might be.

Could you imagine a 6-month boost or 12 months or annual boost?

Yes. I think we're -- the data that was shown was a 6-month homologous boost data. I think Filip has talked about, we're going to be running a clinical trial in the fall is going to be looking at heterologous boost. And so we see significant value in a 6-month boost strategy as confirmed by the data. But we'll have to wait to see what the likes of ACIP and others will say in regard to that.

Okay. And then quickly going on to the MHRA meeting that you -- I think you mentioned later this month or next month. What is the specific question that you're looking to get out of MHRA? Or is it a checkup meeting prior to filing an application for -- or finishing the application for approval in the U.K.?

Yes. This is -- this -- we hope would be the final meeting where we would have the submission after that. We're looking at the final questions that they come up with and leading to a filing in September.

Last question regarding influenza. I'm quite interested in seeing that move forward. I think it may be interesting to see a combination vaccine. And I guess I'm wondering when you consider the results that you have with the quadrivalent vaccine, what do you think was the driver of the influenza or the response? Was it Matrix-M? And could you speculate on what the response might look like when you combine with 2373 with NanoFlu?

Yes. This is Greg. I mean I just -- I think we have 2 sets of data now. So 1 is a very efficacious COVID vaccine with Matrix-M. And previously, as you know, we had really good success in older adults with our NanoFlu vaccine.

In this trial, this is a licensed vaccine given during the administration. And I think it showed to us that you could give a very good flu response and COVID response simultaneously. So we're looking forward to -- I think we're staying with our expectation as this fall, we'll be starting our combination flu COVID vaccine with Matrix-M. And we know Matrix-M has some really good future that creates a better quality and quantity of immune response.

I think that COVID has really proven the technology can be very powerful for protection against these respiratory vaccines. And I think flu, there has been the gap improving immune response, improving the efficacy with flu would be our expectation with this combo vaccine. So we're very excited to get that program into the clinic, and I expected that as we've said, I think that sometime this fall, we'll enroll our first subject in the combo trial.

And our next question will come from Vernon Bernardino with H.C. Wainwright.

Congrats on the tremendous progress. I know it's been a long trip and I've been there with you and reading all the way. I know you just announced the submission for EUA, India, Indonesia and the Philippines. But can you give us an idea how long the regulatory process takes in those countries? And do you -- can you provide any insight in how many doses have been already distributed by others and other vaccines in those geographies and perhaps by the time 2373 becomes available in India, Indonesia and the Philippines?

So I can speak to Indonesia. I think that they have had about 70 million doses distributed to date. A lot of those vaccine doses are for the Sinopharm, which is the inactivated vaccine and countries have expressed real interest in trying to have a booster with a vaccine like ours. So we did -- we have been approached by their government or at least our partner, Serum, was approached by Indonesia because of their extremely difficult situation they're having with the delta virus vaccine.

And I guess when I looked at the data we had today with boosting, it was very encouraging to see how good our immune response was with delta. And we can't predict the timing of these regulatory interactions very easily. We're hoping that something fairly soon could happen. But right now, we just don't have a prediction for the timing of their actions.

Okay. And as a follow-up to that, I know that you're going to manufacture 350 million doses and SII will manufacture the balance of the 1.1 billion. How much of those doses will be going to 3 countries?

Yes. So we don't -- so COVAX controls -- Gavi controls it, Gavi and UNICEF. So we don't have -- currently, we don't know the order in which they want to provide doses for through the COVAX Facility.

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

I guess with respect to the equity filings with EMA and MHRA can you -- I'm sorry if I missed it, but can you speak to what extent the submission packages or requirements differ from those already submitted with Serum Institute for India, Indonesia and the Philippines? Or I'm just curious to know whether you're seeing European regulators move the goalpost at all, given that it's kind of taken this long to complete those submissions?

And then, Stan, you sound fairly confident on the authorization path remaining opening in the U.S. following the approval -- potential approval of the mRNA vaccines. I'm curious to know if there's any other feedback specifically from the agency that gets you comfortable with that windows getting open through the fourth quarter. And whether or not it does, we'll be curious to get a sense of how to think about time lines to a BLA filing with 2373?

Yes. So a couple questions there, but my confidence in my statement is generated by news articles. Peter Marks and before that -- before I read that quote, I would have said we can't predict whether the EUA -- it's been a question mark for a bunch, whether the EUAs going to remain open. And when Peter Marks said that it will remain open in particular because we want to get a protein-based COVID vaccine through the system. My confidence went up a lot. And so that's what I base it on.

On the regulatory issues. So every -- so we have made products in different plants and use it in different clinical trials. And what is the only difference between what we're filing with everybody else and what we're intending to file with the MHRA and EMA is we're finishing up some comparability work between lots that needs to be done. And those -- I think the actual studies are done, and they did as we put together, and that's what's going to take, getting the data put together and submit it to the MHRA. And so it's -- I have a great deal of confidence that, that package will go into them on the timetable we just talked about.

How are you planning to update investors, I guess, as it relates to those package submissions?

Well, I think when -- obviously, when we get an approval, you'll get a press release. And I think when we file with major agencies like MHRA and EMA will announce that in the press release.

Okay. And maybe just 1 follow-up, if I could. I'm just trying to understand -- better understand some of the language in the most recent filing here. As it relates to your agreement with the U.S. government saying that it would like to see FDA alignment on your analytical methods before conducting additional U.S. manufacturing. And I guess how do I understand that? Is that suggest some kind of optimizational approval before continued U.S. production? And would it have some variants...

That's sort of the source of some of the delay with the FDA as we have this USG, the U.S. government, that is our partner in developing this vaccine, and they are the gate to our submitting to the FDA. So there has to be some negotiation with U.S. government and does the validation activities meet their standards and then we take it to the FDA. And there's always a time lag with the FDA these days. And so -- It's -- but we need -- but they want us to get FDA concurrence that our assay is fully validated, and that's what the time difference is.

Okay. Would this have any impact on the originally planned delivery of the 100 million doses under the original warp speed agreements now that you are originally expecting delivery in the first half of '22?

Sure, it does. Because the original timetable calls for starting to deliver those doses in the fourth quarter and through the second quarter of next year. And I think that probably we won't get any doses shipped in the fourth quarter, and it will just push it back to the first and second quarter. We've stockpiled those doses. So it's -- they will come in a rush once we get the FDA approval.

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

Yes. This has been a huge transition quarter for the company. I mean getting regulatory submissions is huge. We're on the verge of product approval. We believe we have additional -- we've demonstrated additional demand for the product and with the EU filing, and we've got great data that shows our vaccine is effective against the various strains. And so we're very optimistic and we look forward to reporting to you next quarter. Thank you.

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