Novavax, Inc. (NVAX) Q1 2021 Earnings Report, Transcript and Summary

Good day and welcome to the Novavax First Quarter 2021 Financial Results and Operational Highlights Conference Call. [Operator Instructions] Please note this event is being recorded. I would now like to turn the conference over to Silvia Taylor, Senior Vice President, Investor Relations and Corporate Affairs. Please go ahead.

Good afternoon, and thank you to everyone who has joined today's call to discuss our first quarter 2021 operational highlights and financial results. A press release announcing our results is currently available on our website at novavax.com. An audio archive of this conference call will be available on our website later today. The presentation slides we will be using for this call are all on our website in the Events section. Joining me today are Stan Erck, President and CEO, who will provide an overview of our progress in the first quarter as well as updates on the regulatory time lines in our manufacturing scale-up. Additionally, Dr. Greg Glenn, President of Research and Development, will provide an update on our global clinical development. John Trizzino, Chief Commercial Officer, Chief Business Officer and Interim Chief Financial Officer, will provide an update on our supply commitments and financial results for the quarter. Additionally, Dr. Filip Dubovsky, Chief Medical Officer, 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 that could include financial, clinical or commercial projections. Statements relating to future financial or business performance, conditions or strategies and other financial and business-related matters, including expectations regarding revenue, operating expenses, cash usage and clinical development and anticipated milestones, are forward-looking statements within the mandate of the Private Securities Litigation Reform Act. Novavax cautions that these forward-looking statements are subject to numerous assumptions, risks and uncertainties, which change over time. I would now like to hand the call over to Stan. For those of you following the accompanying slides, please turn to Slide #3.

Thank you, Silvia, and thank you to everyone for joining us today. In the first quarter, we built on our many achievements of 2020 -- every aspect of our business. I'm proud to say we remain tireless in our efforts, delivering on key clinical milestones, advancing efforts to ready our global supply chain for commercialization and progressing 2373 towards regulatory authorization around the world. I'd like to begin today's call by first providing a recap of some of our key achievements in the first quarter, including the fall. We announced both interim and final analyses in our South Africa Phase IIb and U.K. Phase III trials. We demonstrated 2373's favorable safety profile, immunogenicity and outstanding efficacy against multiple strains of COVID-19. We continue to advance our PREVENT-19 pivotal Phase III trials in the U.S., including expanding the study into pediatric populations. We initiated multiple crossover and booster arms in order to refine our visitor strategy, which will be key to our future. We leveraged our platform to advance the development of both our variant strains combination vaccines into preclinical studies. In our global supply chain, we expanded our global presence with new manufacturing agreements as well as advancing our existing partnerships. We successfully began GMP manufacturing at commercial scale at all of our sites. We secured additional supply agreements including finalizing an APA with Gavi for a commitment of 1.1 billion doses to address global equitable access to our vaccine in partnership with the Serum Institute of India. We'll talk later about this. We progressed our dialogue with regulatory authorities globally, making significant progress towards completing CMC and the remaining clinical requirements. Today, we are pleased to share more details on our recent progress. I will ask other members of our management team and talk about our clinical progress and plans, about the status and expectations that we have for advanced purchase agreements during this pandemic period, stretching over the next couple of years, and about our financial performance in the first quarter. Then I'd like to take back the microphone to cover a couple of important areas. Point 1, I'd like to update our guidance on a couple of near-term deliveries that we get daily questions on. And point 2, I'd like to start focusing the attention of our investors on what the mid to longer term outlook looks like for Novavax. It's a picture that is very compelling. With that, I would now like to hand it over to Greg Glenn to discuss our clinical developments in the first quarter. He'll be followed by John Trizzino and then all rejoined.

Thanks, Stan. Turning to Slide 4. In the first quarter, we made excellent progress in advancing 2373 through our various clinical trials. As Stan mentioned, we announced both interim data and final analyses for our South Africa Phase IIb and U.K. Phase III trials, rapidly completed our enrollment of our PREVENT-19 Phase III trial and initiated a number of other studies building on the excellent safety and efficacy data generated to date. In the next few slides, I will give an overview of these key clinical developments from the quarter as well as discuss our upcoming clinical milestones. Beginning with our South Africa Phase IIb trial on Slide 5. In the complete analysis from this trial, which included over 4,400 participants, 2373 achieved its primary endpoint, demonstrated overall efficacy of 48.6% and efficacy of 55.4% amongst HIV negative trial participants. We also confirm II/III efficacies against the B.1.351 variant first identified in South Africa, demonstrating approximately 51% efficacy against mild, moderate or severe disease against this variant in HIV negative participants. Importantly, there were no severe cases in the vaccine group and 5 severe cases, including 2 deaths, in the placebo group. Four out of 5 were due to the variant of concern, B.1.351. Last week, full results from our South Africa Phase IIb study were published in the New England Journal. Now moving to Slide 6. You can see a summary of results from the final analysis of our U.K. Phase III trial, which included over 15,000 participants. In this trial, 2373 achieved its primary efficacy endpoint, demonstrating overall efficacy of 89.7%. The final analysis also confirmed 2373's high efficacy against multiple variants of COVID-19, demonstrating 96.4% efficacy against the original COVID-19 and 86.3% efficacy against the B.1.1.7 variant, first identified in the U.K. The final analysis also showed that 14 days after 1 dose, vaccine efficacy was 83.4%. In participants 65 years of age and older, we demonstrated a vaccine efficacy of 89%. And finally, over 40% of the study participants in this trial had medical comorbidities that placed them at high-risk for severe COVID disease. Among this group, 2373 demonstrated a 90.9% efficacy. We view this as particularly important, illustrating 2373's ability to protect a portion of the population at high-risk for COVID-19 disease. Our results from this trial have been submitted for publication in a peer-reviewed journal and posted to net archives. In summary, on Slide 7, 2373 has shown excellent efficacy in trials conducted in settings where both the original and variant strains were circulating. Importantly, in both trials, 2373 demonstrated 100% protection against severe disease and it was well tolerated. Adverse events were balanced between the vaccine and placebo group. At this time, we have also initiated crossover arms in both trials, which will help further inform our booster strategy. Now turning to our PREVENT-19 Phase III trial in Slide 8. In the U.S. and Mexico, where we are conducting this trial, we announced that in February, we had completed enrollment for this trial -- this Phase III trial. The notably diverse study population included 30,000 participants from a wide range of demographic backgrounds as well as individuals who are at high-risk of COVID-19 due to factors such as medical comorbidities or age. At the end of April, we also implemented a blinding crossover allowing all subjects in our PREVENT-19 trial to receive active vaccine. The successful conduct of the trial will allow unblinding for a final analysis as opposed to an interim analysis, based on the events we've accrued prior to crossover as the trial is well powered to describe efficacy. Stan will discuss the timing of announcements in more detail later in the call. The updated protocol has been posted to our website today. Moving to Slide 9. PREVENT-19, which have been enrolling U.S. participates in December of last year, was also conducted in the context of a rapid emergent of variant strains. By the end of April, at the close of the endpoint accrual period, we've seen the rapid rise of B.1.1.7 strain. This variant now accounts for over 60% of the U.S. cases. But as I mentioned, in our U.K. Phase III study, we showed that 2373 was 86% effective against the B.1.1.7 variant and 96% effective against the original strain of COVID-19. And now turning to Slide 10. We also initiated a pediatric extension of PREVENT-19 in April. On this slide, you can see the study design, which includes 3,000 adolescent participants, 12 to 17 years old, across 75 trial sites in the U.S. 2/3 of the participants will receive 2373 and 1/3 will receive placebo in order to evaluate the efficacy, safety and immunogenicity of 2373. We see this as an important step towards expanding the reach of our vaccine and making progress towards ending the pandemic. We expect to implement a blinded crossover of 6 months after the initial set of vaccinations. In parallel with advancing 2373 through our various efficacy trials, we saw significant progress in 2 other areas of our clinical program in the first quarter. Our variant strain, COVID-19 variant vaccine and combination vaccine candidates. I would like to briefly touch on our recent developments of these 2 programs. Last week, we shared preliminary data at the World Vaccine Congress from a preclinical study of our B.1.351 candidate, which you can see on Slide 12. As a part of this work, primates who originally received a 2-dose regimen of 2373 last year were boosted 1 year later with our B.1.351 candidate, containing Matrix-M adjuvant. Data from this study showed within 7 days of receiving the B.1.351 booster, animals exhibited strong functional immune response. Immunity debt, as we showed at the World Vaccine Congress, can block 1.351 spike from binding to ACE2. We'll have more to say on this work in the coming weeks. Finally, turning to Slide 13. We also dedicated significant efforts during the quarter to exploring various combination vaccines, including a combined NanoFlu 2373 vaccine candidate, all combined with Matrix-M adjuvant. We recently completed a preclinical study of this combination vaccine to assess its immunogenicity and protective efficacy in animal models, and the data are summarized in the manuscript posted to bio archive. Briefly, we found that the combination NanoFlu 2373 vaccine induced strong functional antibodies in ferrets with hemagglutinin inhibition antibodies and ACE2 receptor inhibiting antibodies that were comparable between immunization with both a combination vaccine and respective component vaccines. In these animals, the combination vaccine induced high levels of anti-spike and neutralizing antibodies. When immunized hamsters were challenged with SARS-CoV, the quadrivalent and 2373 combination vaccine showed protection which was not diminished compared to the 2373 alone. No viral replication was detected 4 days after the COVID challenge and the lung showed no changes. These results demonstrate that a novel combination of flu COVID vaccine has the potential for a transformative impact on both diseases. We expect to bring this candidate into clinical trials later this year. I would also like to highlight on Slide 14, ongoing clinical trials conducted by our partners, reflecting collaboration around the world for development of our COVID vaccine. These include both a Phase I/II trial conducted by Takeda in Japan as well as a Phase II/III clinical trial conducted by the Serum Institute of India to evaluate the safety and immunogenicity of 2373. These trials were initiated in the first quarter. Enrollment is complete in the Takeda trial and enrollment is about to begin in the Phase III portion of the Serum trial. We look forward to sharing additional updates as these trials progress and expect these clinical trials led by our partners will play a meaningful role in promoting global access to our vaccine. Next, I would like to discuss the combo study, which was initiated in April. This is a U.K. government-sponsored study being conducted by the University of Oxford that will assess 2 dose priming and boost regimens of COVID vaccines, mixing the AZ, Pfizer, Moderna and Nova vaccines in various combinations, given 8 weeks apart. The study will evaluate the safety and immunogenicity with results expected in the third quarter. We also wish to highlight an exciting collaboration regarding an important advance in malaria prevention. The University of Oxford's malaria vaccine candidate R21, which includes our Matrix-M adjuvant, has been advanced through a Phase IIb clinical trial conducted in a study population of 450 children, ages 5 to 17 months. In April this year, we announced a publication of the data from this trial in Preprints with The Lancet, where R21 demonstrated 77% efficacy. These landmark results underscore the potential for this vaccine to serve as a tool to help control malaria globally. Clinically -- clinical development of this vaccine candidate continues with a Phase III licensure trial underway in 4 countries in Africa to evaluate the safety and efficacy of R21 in 4,800 participants, ages 5 to 36 months. We look to the commercial potential of this vaccine and we supply Matrix-M adjuvant to the component to Serum Institute of India, who will manufacture the R21 vaccine. In efforts to ensure widespread distribution, Serum Institute has granted rights to use -- has been granted rights to use Matrix-M adjuvant in the vaccine in endemic regions and will pay Novavax royalties on its market sales of the vaccine. Novavax will have rights to sell and distribute the vaccine to travelers in military vaccine markets. With that, I'd like to turn it over to John to discuss our key supply developments for the quarter.

Thanks, Greg. Turning to Slide 15. You can see a snapshot of our global supply commitments to date as well as our licensing agreements. With this as a backdrop, let me state that in the quarter, we saw that the urgency to make 2373 available globally only intensified amidst the backdrop of the evolving COVID-19 pandemic. Today, there continues to be a vast need for equitable distribution of COVID-19 vaccine. While the U.S. has fully vaccinated 35% of all adults greater than 18 years of age, demand outside the U.S. far outpaces supply. This unmet demand across the globe reinforces the importance of bringing our vaccine to market and has resulted in continued demand for 2373 now and through 2022, which we believe reflects the continued confidence in 2373's ability to combat the pandemic. Our commitment to the principles of fair and equitable access to 2373 that includes supplying vaccine to low-, middle- and high-income countries remains at the core of our values. In light of this, we were happy to announce last week the finalization of an advanced purchase agreement with Gavi, expanding upon our memorandum of understanding announced in February. Under the agreement, we have committed cumulative 1.1 billion doses of 2373 through the COVAX facility. We expect to manufacture and distribute 350 million of these doses, utilizing antigen and adjuvant manufactured at facilities directly funded by previous investments from CEPI. Under a separate agreement with Gavi, Serum Institute will manufacture and distribute Novavax licensed product for the remaining balance of the 1.1 billion doses for low- and middle-income countries participating in the COVAX facility. Together with Serum, we expect to begin delivery of doses in the third quarter of 2021, dependent on the appropriate regulatory authorizations. In the first quarter, we also finalized an advanced purchase agreement with the Government of Canada to supply 52 million doses with the option to purchase an additional 24 million doses. We also announced our intention to transfer our technology and partner with the Government of Canada to explore opportunities to manufacture our vaccine at the National Research Council's Biologics Manufacturing Center. As of today, in addition to our advanced purchase agreements with Gavi, our bilateral advanced purchase agreements total approximately 200 million doses committed to countries around the globe. In addition, we continue negotiations with the European Commission on behalf of the 27-member states for a potential supply agreement. We are pleased with our progress to date, and we will share additional details as these discussions reach finalization. Based on the many inquiries over the past year and those ongoing discussions, we understand that the COVID-19 pandemic and demand for vaccine is here to stay. We will continue to support this demand in the years to come. As such, we are currently negotiating a number of other supply agreements with countries globally that are looking to secure a vaccine for 2022 and beyond. Given the need to complete the primary vaccination in most countries, the demand for 2373 remains extremely high. With that, I would now like to turn to Slide 16 to review our financial results. Today, we issued our first quarter earnings release, which walks through the details of our financial results for the quarter. We also filed our 10-Q for the first quarter of 2021 today. This includes details on important business and financing events, during and subsequent to the first quarter. Notably, Novavax revenue in the first quarter of 2021 was $447 million compared to $3 million in the same period in 2020. This significant increase was due to the increase in research and development expenses to $593 million relating to the 2373 activities performed under the U.S. government and CEPI funding agreements. We raised net proceeds of approximately $565 million during the first quarter through utilization of our ATM offerings. The quarter ended with a very strong cash position of over $2 billion compared to over $800 million at year-end 2020. This increase in cash was primarily due to $772 million of payments received under advanced purchase agreements and the $565 million of ATM funding just referenced. With that, I'd like to hand it over to Stan to discuss some of our updated timing and guidance as it relates to our upcoming lifestyles.

Thanks, John. Okay. So let's turn to slide 17. And on this call, we've reviewed a long list of recent successes, including their clinical safety and efficacy data. Now I'd like to talk about the near and midterm focus of the company. And I'd like to start by addressing the questions that we get asked every single day with the goal of updating our guidance for the short term. First question we always get is when can we expect to see the results from the U.S. Phase III efficacy trial? The second is what is the timetable of regulatory filings in the various parts of the world? And the third is what is the trajectory for scaling up our manufacturing on a global basis? Let me take them one at a time. Unblinding U.S. Phase III trial -- let's start with the timing of the U.S. Phase III trial. So please turn to Slide 18. We have previously guided that we expect to unblind the trial in the second quarter of this year. And based on the timing of the unblinding of our South African and U.K. trials, I think that a lot of people have an expectation that we might be able to unblind the trial in April. But instead, we initiated a blinded crossover in this trial in April for which we show the study design on the slide. We believe implementing the crossover and thus bypassing an interim unblinding will actually give us a comprehensive data set more quickly. This gives us the ability to collect more cases, increasing the robustness of our data set when measuring efficacy against factors such as severe disease and against variants. We continue to guide that we will announce our Phase III clinical data in the second quarter. We look forward to sharing our results with you in a few weeks. So with respect to regulatory authorizations, moving now to Slide 19. Our timetable for regulatory filings, we know that we're delayed from where we thought we'd be at this point. But now we're giving guidance that nearly all of the major challenges have been overcome and we can clearly see the light at the end of the tunnel. All facilities in our network have already demonstrated the ability to manufacture commercial scale GMP material. The filing timetable depends on completing the final phases of qualification and validation of the assays that are needed to complete the demonstration of process consistency and to subsequently finalize the reports for regulatory filing. It has been a massive effort and has dependent on our global manufacturing partners to help us accumulate a suitable data package. And not surprisingly, it is currently the top priority of the company. It is not likely that we'll finish this work in time to submit by the end of June, so I'm changing our guidance to reflect that we expect to complete our regulatory filings in the third quarter. We are planning multiple filings that will be made with the U.S. FDA, the U.K. MHRA and with the EU EMA as soon as our data packages are complete. In other markets, we will continue our rolling review processes initiated earlier this year, including with Health Canada, Australian Therapeutic Goods Administration and New Zealand MedSafe. Additionally, we anticipate starting rolling submissions to WHO for emergency use listing. A rolling submission process is also underway with the Republic of Korea's Ministry of Food and Drug Safety, which SK Bioscience initiated in collaboration with Novavax in April of this year. These regulatory authorities will all complete their reviews of our submissions on their own timetables and we hope to have market authorizations in multiple countries during the third quarter. As of today, we are not able to predict a date with precision, so we won't. It is in everybody's interest to push to make this happen as early in the quarter as possible. Let me next discuss the current state of our manufacturing and our anticipated capacity as we look to the remainder of the year. Please turn to Slide 20. On our last earnings call, we discussed the significant strides taken in 2020 to build out our global supply chain as seen on our global supply chain map. Some of the key manufacturing developments included reaching an agreement in principle with GSK to support fill and finish manufacturing of up to 60 million doses for use in the U.K., establishing manufacturing capabilities in Canada through our memorandum of understanding with the Canadian government to produce 2373 at the National Research Council's Biologics Manufacturing Center, finalizing exclusive license agreements with both Takeda and SK Bioscience in Japan and South Korea respectively. Today, our global supply chain now spans over 10 countries with all of our manufacturing sites producing GMP material at scale. I think we've done a remarkable job of standing up manufacturing in these multiple plants across the globe. I'm happy to report that we have got to the point where we've successfully manufactured our drug substance, a recombinant protein nanoparticle, at commercial scale in each of these plants. The drug substance production is the most complicated step in the overall manufacturing processes. Our guidance has been that we would be at full operating cadence by the end of the third quarter. As has been fairly widely reported, we are having difficulty getting to that point due to a global shortage of a few raw materials, including a shortage of 2,000-liter bags, depth filters, which are used in the purification process and then growth media. As closely as we try to manage these materials, we have been running into shortages that has cost us to delay production runs. Our expectation is that our suppliers are adding sufficient capacity such that we will be operating at full capacity, but likely not until the fourth quarter. We expect we will be at full capacity throughout 2022 and beyond. The impact on us will be a somewhat slower rollout on product approval, but not dramatically. We are building inventory of our drug substance and the adjuvant as we speak. We have tens of millions of doses made already and will continue to produce approximately 100 million doses per month by the end of the third quarter. These will be ready to go and when we get our regulatory authorizations. So now let's turn to slide 21. Let's look at the next 6 to 12 months. With licensure expected in the third quarter, at least in some parts of the world, we will begin shipping product. With our new agreement with Gavi and the COVAX facility, our doses over the next 6 to 12 months may be prioritized to lower-priced countries. We have taken this position because we think it's the right thing to do and is in line with our original funding from CEPI. I think that it's particularly timely given the discussion around the waivers of IP rights during the pandemic. I believe that we have taken the lead to show the world the right way to get product distributed on an equitable basis globally. We expect that even with early products sold at low prices, we will be able to match that with revenue from higher income countries to be able to generate sufficient cash flow to expand our business rapidly. Beginning in early 2022, we will have a rapid increase in our ability to service our high-income country APAs because of the following reasons: reaching manufacturing capacity of over 150 million doses per month starting in the fourth quarter of this year, including from Serum Institute; increased capacity coming from online, from new manufacturing partners and resolution of any outstanding raw material constraints. With respect to the U.S. market, we are well positioned with our technology and timing to supply product for boosting and seasonal revaccination. In the ex-U.S. market, there continues to be variability with many countries continuing to have very low vaccination rates. Therefore, significant unmet demand remains globally that we will be able to support 2022 and beyond. This will continue to include the supply to high-income markets from our facilities, and we expect low and middle-income countries to be supported by Serum. Over the next 4 to 6 quarters, we expect all of these factors to contribute to Novavax generating billions of dollars of revenue. We plan to be in the clinic with our variant strain antigen in the fall and data will come soon after that. We can then determine our best path forward for our booster or revaccination strategy. That strategy will be dependent on durability of protection and ongoing variant strain surveillance. We'll sort that out and make the right call at that time. Longer term, we expect to upgrade our vaccine to be combined with flu, which will require further expansion of our production capability, which is something we think our platform is unique in being able to do. We initiated this program late last year and published data last week showing that in an animal model or combination NanoFlu COVID vaccine was able to elicit strong antibody levels to both flu and the coronavirus. And when the animals were challenged with coronavirus, they are completely protected. This has the potential to be the standard for seasonal respiratory vaccines. With a single vaccination using our same platform, we could have a vaccine that elicits broadly neutralizing antibodies, is efficacious against both coronavirus and flu, is stable, and can be made and formulated at large scale. That would require running trials with the combination COVID flu vaccine. That's been hard for us to start up because we haven't had the benefit of our own production capabilities and our contractors are all focused on COVID. But we will be able to get a combo vaccine into patients' arms by the end of this year. Just to confirm that the formulation has affected us apart, I would guide people to think about the launch of such a combo vaccine out in 2025. So even if you see other well tolerated protein adjuvanted vaccines compete with us for the COVID-only market in the next several years, we think that our unique COVID flu combo will come out on top in the long run. In the future, as we generate significant revenue in our production facilities come online, you'll see us use our capital, our people and the labs to produce more vaccine programs that our team has long been hoping to work on. This is just the beginning for Novavax. In all cases, we will continue to build these vaccines on the platform that has consistently shown competitive advantages, including the development of broadly neutralizing antibodies with the potential to protect against a wider range of variants, both in COVID and in flu, a stability profile that allows for the refrigerated shipment of storage of vaccine, a safety profile that leads to fewer side effects and with our combination vaccine, the potential to protect against multiple infectious diseases with a single vaccination. Turning finally to Slide 22. With another successful quarter, strengthening every aspect of our business, we are rapidly advancing toward our mission of delivering 2373 globally. With that being said, we recognize the need to seamlessly deliver on our more near-term milestones ahead, including executing in our clinical trials, finalizing preparations to ready our global supply for commercialization, obtaining regulatory authorizations for 2373 and advancing our variant strain in combination vaccines in the clinical development to most effectively address the evolving pandemic. Before opening up the call to Q&A, I want to thank our entire Novavax team for their continued dedication and tireless efforts over what was once again a very busy and productive quarter. These efforts, combined with the support of our partners globally, have brought Novavax significantly closer to delivering our COVID-19 vaccine. I will now turn it over to the operator for Q&A.

[Operator Instructions] The first question comes from Kelechi Chikere with Jefferies.

Just a couple on my end. I guess, first, can you give us an idea or additional color on how much vaccine that you have actually stockpiled? And I guess also related to that, how much are you actually producing per month currently?

Yes, it's a good question. This is Stan. And it varies quite dramatically by site, by month as we either have raw material supplies or not. We -- as I mentioned to you that in the third quarter, we had expected to be able to produce roughly 70 million or 80 million doses per month at the Novavax sites, excluding Serum. And I would guess that we're probably in half that right now. We've made 30 million or 40 million doses on the shelf and it's getting larger every week.

The next question comes from Charles Duncan with Cantor Fitzgerald.

Team, congrats on a good quarter of progress. Thanks for taking my questions. I have a couple of them. The first is, I'm wondering if you can provide any additional color on the U.K. emergency use authorization? And then secondarily, maybe a perspective on emergency use authorizations versus, say, full authorization. I guess, I'm wondering, do you prefer to stick with an EUA approach for countries outside the U.K. and others that you filed? Or would you pursue a full authorization?

Okay. Yes. So U.K. -- U.K. has been -- we've worked closely with a lot of these groups. U.K. we've had the most dialogue with and I think the expectation we had -- always had was that we would try to get a filing into the U.K. with the full CMC and clinical package by the end of June. That's now moved into July. I think the MHRA is paying close attention and is likely to be the first approval and authorization, I guess, is the right word. And so it could be others like Korea just at the same time, I think.

And just as far as the EUA versus final approval, we think that emergency use of conditional authorization is on the route to getting full approval. And that's just because the safety data needs to mature to have a complete package to allow for final approval.

Yes. So everything we're putting in for the EUA is relevant to the BLA.

And then moving on to PREVENT-19. In terms of the crossover, could you just help me think through kind of the strategy there? It seems like the crossover eliminates the control arm. And I'm just really wondering what you're hoping to learn from the crossover? Or is it just a way to increase the number of patients that have been exposed to full -- fully vaccinated?

Yes. So the situation in the PREVENT-19 study was complicated by the fact that a lot of emergency use vaccine was made available in the U.S. and the U.S. public health system was advocating its use. So for us to maintain the integrity of the study, we had to take on a strategy where we would provide vaccine to all the participants. And the most rational way to do that would be through a crossover. This allows us to also look at waning of protection by comparing the people who are initially vaccinated with those that are vaccinated in the crossover design. We're going to get a lot of information from the study, including a larger safety database. But importantly, we are going to have enough cases, as Stan reported, prior to crossover for us to be able to have a final analysis in the second quarter.

Okay. Final question regarding perhaps the future strategy of combining COVID vaccine with an influenza vaccine or NanoFlu. I think Stan, you mentioned perhaps being able to market that in 2025. I'm wondering what are the rate-limiting steps to getting there. And we've got several seasons beforehand and it seems like that would be a pretty interesting combination of vaccines. So what needs to be done to get there?

Well, it's generally clinical development, but…

I'll take a crack at it there. There are a couple of issues. One of them is if you've been watching the influenza epidemiology, you will have seen that flu has disappeared this season. And we need to understand how it's going to turn back to its normal cadence before we plan to do any kind of efficacy evaluation, naturally only in our own studies where we think we can get a result. And for that, we need to understand when flu comes back and how it will come back. So that's an important bit of information we need because we need to compare the combination vaccine to the 2 individual components. We'll get the efficacy results for COVID, while we already have them from the U.K. and South Africa. And we'll get confirmation from the final Phase III study in the U.S., but we also need efficacy results from the NanoFlu so we can use it to leverage the combination product.

Do you anticipate a trial -- I think you had mentioned of a trial perhaps even starting this next flu season for the Northern Hemisphere or the follow not?

Immunogenicity trial.

So it’s immunogenicity trial starting in the fall.

The next question comes from Eric Joseph with JPMorgan.

First, on manufacturing, Stan, if I heard correctly, you have 30 million to 40 million doses on the shelf currently. That would seem or sound well below the target of 110 million doses by the end of the quarter to satisfy OWS. So I'm just wondering what the impact might be to remittance or follow through on that award, whether any of that payment is at risk? Secondly, on PREVENT-19, it sounds like you had some visibility on a net accrual rate in initiating the crossover trial portion. Can you just say clearly whether or not you've already conducted an interim efficacy analysis or pretty much what prompted the move to initiate the crossover portion of the study at that time? And then finally, given some of the challenges in sourcing of raw materials to complete manufacturing, how should we be thinking about the impact to product margins from where things stood at the beginning of the year?

Yes. Let me take the manufacturing-related ones. I think that U.S., we -- I think our expectation is we'll have the 110 million doses made right around the end of the year, the first/second month of next year. So that will take that. The impact of cost of goods sold is -- it's not a long-term impact at all. I think it's -- if you're not running a plant, the first product you make costs a lot. But if you're making a regular cadence, the cost of goods sold should be where it always is. And so I'm not worried about our cost of goods sold margins.

And as far as the crossover, like I mentioned before, the real reason we did it was because EUA vaccine came available. In our other studies, for instance our Phase II studies, about 60% of the people have dropped out to receive EUA vaccine. So that was the real driver for us to maintain the integrity of the study.

Okay. I mean, really just a follow-up on Charles' question, it seemed like that might sort of invalidate the placebo arm. Do you -- I guess, what proportion of patients from the study have -- do you expect to cross over? Are you -- how do you maintain confidence that you'll still be able to accrue the dose primarily on the placebo arm?

The primary efficacy is obviously conducted prior to crossover where there's a placebo comparator. And that's going to be the final analysis. We didn't conduct an interim -- this can be a single analysis. It can be conducted on a data set. All of our alpha is going to be used against that endpoint. So we're going to have a more precise estimate of efficacy. And that data will be available before the end of this quarter.

The next question comes from Mayank Mamtani with B. Riley FBR.

Appreciate the comprehensive update. My questions are mostly the specific follow-ups to previously-asked questions. So maybe just, Stan, starting from the nonclinical CMC manufacturing components of the submission, are you able to comment on what might be these sort of things that are causing the holdup? Is it just process coordinating between the different sites? Or are there any specific issues around any particular assay? So if you're able to comment on that, that would be great.

No. I mean, and part of it has to do with manufacturing at different sites and showing comparability between the processes and the actual end product between the different sites. And you have to develop assays that can follow those. And so I think it probably took a little longer than we expected to get a potency assay that was worked across -- told the same story across all the sites. But I'm happy to say we did. We've crossed that bridge. We're -- we made a big breakthrough there and we're now racing towards validating everything and putting it into a package.

Okay. And then on the protocol amendment, I'm sorry if I shouldn't be calling it an amendment for PREVENT-19 study, could you just verify the final event rate is still -- I think 144 cases, I guess, will be -- was what we had in the initial protocol? And then my more important question is, as you know, the label for some of these EUA approved vaccines will start to look more specific to a booster going into the fall. So are you able to comment what could be gleaned out of PREVENT-19, if anything, around your booster strategy if at all?

Okay. Let me take that in 2 bits. First, as far as the number of cases, the previous version of the protocol called for an events-driven analysis. We're not there anymore. And we weren't there because, like I explained, we had to adjust the study to maintenance its integrity. So now it's a time-based analysis. It's going to be done on events that were collected prior to crossover. And that's going to be the total number of events we have in our analysis, and that will address our efficacy in that label.

As far as the other question about boosting, nothing from PREVENT-19 will speak directly to boosting. The data we have on boosting is coming from our Phase II study where we've just completed a 6-month boost of people who are initially vaccinated, both with 1 and 2 doses. Additionally, it will come from the South Africa study where people who receive 2 doses are getting a single boost dose in that context. So those are the -- that's the main data we're going to have to talk about boosting in addition to all the really compelling preclinical data that Greg shared with you previously.

I guess a natural follow-up to that is, can that be part of your regulatory submission? The U.K. COMCOR data, the South Africa data, those elements, do they make sense to be part of your regulatory package?

I think in the initial filing, our main intent is to get primary licensure with the vaccine we have in hand. And a booster trial's use is going to be considered as that data matures and is available. It's my thinking we're going to be filing in advance of having that data mature. So it will come on as a variation or as an imminent to that file.

Okay. Great. And then final question. On the -- so Stan, you gave color on the monthly run rate getting to 150 million in fourth quarter. Any commentary you can -- I know you used to talk about the annual run rate also? And if you're still guiding to that -- getting to that 2 billion doses mark. And I understand that includes contribution from Serum for about 1 billion, which you seem to be picking up some slack near-term for Serum. So any color on when you can get to that 2 billion doses a year run rate, just factoring in Novavax and your partners' capacity?

Yes. I think we will be there by the end of this year and expect to be there throughout the entire 2022.

The next question comes from Vernon Bernardino with H.C. Wainwright.

Congrats on the tremendous progress. One question I had is, given the U.S. currently appears to be a flush of vaccine doses. Once you have authorization to provide the 110 million doses promised to the U.S. government, do you anticipate the government to distribute those doses in the U.S. or outside the U.S.? Or is this a buy agreement one that allows you to perhaps change it to one with potential stockpiling like a place marker for a future COVID-19 vaccine against an emerging variant?

Yes. I think all of the above. I don't think we know -- I don't think anybody has determined what the fate of those 110 million doses are. And that's a discussion that we will have.

Okay. And then given the promising results with your RSV vaccine, ResVax, although the data are from a small sample, even one looks like promising data in women who got vaccinated while pregnant, do you anticipate conducting a maternal unitization study with 2373?

Right now, our main focus is -- in the pregnant population is to really do what some of the other sponsors have done. We're planning a registry at the far end to capture those cases and assure safety. We should have a relatively sizable population of pregnant women in our studies right now and we're following them very carefully to build that safety database out as well.

Okay. And then last question and I'll go back to the queue. As you probably know, Moderna's vaccine had a single-shot vaccine efficacy of 43%. Regarding the conduct of PREVENT study, have you had enough subjects not coming back for the second dose of 2373? I assume you have. I asked because data from the Phase I/II showed that while antibody levels at day 189 has fallen below the ranges observed in combos and sera from recovered COVID-19 patients, the IVG levels from a single 2373 dose of 25 micrograms plus Matrix-M might not have been enough to confer protection. Therefore, if you advance the combination of the flu plus 2373 to single shot -- and I saw in the paper that what was used as a primary regimen -- you could have a very differentiated vaccine available when it's ready for commercialization, especially if you met the threshold of 50% vaccine efficacy against severe diseases with a single shot.

Yes. I think those are all good observations. I mean, we'll see. We're going to do a trial in fall combination vaccine and that's one reason we'll learn about. But I think you summarized some of the findings quite well.

And so if I may, just I think, lost to the number. You said that the U.K. drops of 60%?

And that was data from the U.S. Phase II study, although there was a similar proportion in the U.K. Those people didn't drop out of the study, they just saw the commercial-used vaccine. So they're still being followed.

This concludes our question-and-answer session. I would like to turn the conference back over to Stanley Erck for any closing remarks.

Well, thanks, everybody. As we -- every quarter gets more data pointing to a successful vaccine, we're getting close to the end, and -- which is really the beginning for us and that's what we're all racing to do. I think we've eliminated all of the serious hurdles to getting -- risk hurdles to getting to where we need to be to get an improved vaccine. And so we're excited about that and we look forward to shipping our first product. Thank you.

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.