Good day, and thank you for standing by. Welcome to the Bavarian Nordic conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there'll be a question-and-answer session. To ask a question during the session, you will need to press star one on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star zero. I would now like to hand the conference over to your speaker today, Rolf Sass. Please go ahead.
Yeah. Thank you, operator, and good afternoon, and good morning to some of you. Welcome to this strategy update, where we are to present very positive top-line data of our phase II COVID-19 program, as well as an RSV strategy update. Before we start our presentation, I will just briefly run through the forward-looking statements. This presentation includes forward-looking statements that involve risks, uncertainties, and other factors, many of which are outside our control that could cause actual results to differ materially from the results discussed. Forward-looking statements include statements regarding our short-term objectives, opportunities, financial expectations for the full year, and financial preparedness as of year-end, as well as statements concerning our plans, objectives, goals, future events, performance, and/or other information that is not historical information. All such forward-looking statements are expressly qualified by these cautionary statements.
We undertake no obligation to publicly update or revise forward-looking statements to reflect subsequent events or circumstances after the date made, except as required by law. With me here today, I have Executive Vice President, CFO, Henrik Juuel, and President and CEO, Paul Chaplin. I will hand the word over to Paul Chaplin to start the presentation.
Thanks, Rolf, and welcome everyone to our conference call. If you go to slide three, earlier today, we came out with two very important announcements, and I'd like to walk you through both of those, giving you a little bit more background and information. The first was our positive top-line results from our phase II study investigating ABNCoV2 as a booster vaccine for COVID-19. The results I'll walk through in the coming slides, but really are probably the best results we could have expected and really sets itself nicely for moving forward into a fully funded phase III next year. The second bit of news was our plans to move ahead with the phase III for RSV.
As I've been saying for the last couple of months, it's all about time to market, and we really feel that it's owed to our investors and to the public at large that we move this product as fast forward as possible into phase III. This is only possible if we're successful with the capital raise that we announced earlier today. If you go to slide five, this is a slide that we often use to introduce COVID-19, and I think little needs to be said about why we need improved vaccines. You know, the last few weeks there's been nothing but news of a new variant, Omicron, that could be a variant of serious concern.
It just highlights the need for better vaccines with a longer protection, a broader protection that will allow society to get back to normal. On the next slide, just to frame where we are with ABNCoV2, our COVID vaccine. It's a viral-like particle technology, which is extremely powerful platform for presenting highly dense antigen to the immune system. What we've already seen from phase I and animal studies is this vaccine is capable of stimulating very strong neutralizing titers, against SARS-CoV-2. We've shown that unlike other vaccines that are approved or in development, ABNCoV2 is able to stimulate broad neutralizing responses against all the current variants of concern. We've been able to secure funding from the Danish government to the tune of DKK 800 million.
This completely de-risks the program moving forward from a financial point of view, and provides the funds to allow us to execute up until launch, which we hope will be in 2023. Where we are right now is today we're gonna report the top-line results from one of the groups from our ongoing phase II study, and to update you where we are with the trial. Obviously with the positive results that I'll walk you through, we are now moving ahead with the fully funded phase III next year. If you go to the next slide seven, just to remind you of the design of the phase II. There are currently three groups. Two groups will receive a single booster vaccination of ABNCoV2 in people who have been previously vaccinated or who have recovered from COVID.
One group, which we'll be reporting from today, received 100 micrograms of ABNCoV2. The second group will receive 50 micrograms as a booster. That group is continuing to enroll. The third group is the seronegatives group. These are people who have previously not been vaccinated, and they're going to receive two vaccinations of 100 micrograms of ABNCoV2. We will report data from the latter two groups in the coming weeks and months ahead. Today, we're reporting the booster vaccination of 100 micrograms. If you go to the next slide. We actually enrolled 103 seropositive subjects. 23% of these were 65 years or older. 67% had completed the primary vaccination with an RNA-based vaccine and 32% with an adenoviral vector-based vaccine.
One individual had actually recovered from COVID and had not been vaccinated. What we see on the left-hand side, the graph on the left-hand side of this slide, is that the starting titers at week zero prior to the booster were relatively low, and that about 57% or more of the subjects actually had undetectable antibody titers against the various variants or were below the level of quantification, which is that line you see, LLOQ. They had very low titers and titers that were associated with lower levels of protection. To put it into context, titers of 100 have been reported to have an efficacy of around 91%, and titers of 1,000 have been reported to have an efficacy of around 96%.
If you go to the next slide. This is quite a busy slide in terms of data, but I'll walk you through it slowly to try and get the points across. These are the neutralizing titers following ABNCoV2 booster against the Wuhan COVID variant strain. If you look at the first cluster of graphs on the left-hand side, these are all subjects in the group, the whole 103. You can see at week zero, those are the starting titers I've just shown you, week one and week two. By week two, we see a 15-fold increase in the neutralizing titers to levels associated with very high levels of protection. The next three graphs are based on the starting titers. The next cluster are titers or individuals who had titers below the level of quantification, the LLOQ.
Here you can see these are people who desperately need a booster, who have extremely low titers and low levels of protection. Here you can see within two weeks of receiving the booster, there's a 40-fold increase in the level of neutralizing antibodies. The graph on the far right-hand side, these are people who have very high starting titers, higher than the median. These are people who don't really require a booster and already have titers associated with high levels of efficacy. However, two weeks post the booster, they already have. You can see that there's a two-fold increase in their levels. Basically we see very, very strong boosting responses, and obviously the responses are highest in those who have the lowest titers and who are in need of a booster.
We still see significant fold increases even in people who have very high titers against this Wuhan strain. The same trend was seen against all variants. If you go to the next slide 10, this is trying to sum up the data that we see against all the various variants, whether there was a two, four or six-fold increase in the neutralizing titers following the booster. In the top left-hand corner, you have the data from all subjects, irregardless of their starting titer, and you can see the responses against the Alpha, Beta, and Wuhan variant strains. In the bottom right-hand corner of this graph, you can see these are people with the highest starting titers greater than the median.
There you can see obviously the fold increases are slightly lower, as you'd anticipate, because these all people already have high starting titers. If you look at the upper right quadrants, these are people with the lowest starting titers below the lower level of quantification. Here you can see the majority of subjects have a very strong boost following the ABNCoV2 vaccination, and this is true for all variants, Wuhan, Alpha and Beta. If you go to the next slide 11, this is the responses against the Delta variant, which currently is still the major variant circulating around the world. This is singled out as this is a slightly different assay. This is a competition receptor binding assay, which correlates very strongly with the neutralization assays I've shown you before.
This is a very similar picture. If you look at the left-hand side, this is the overall response where you've seen 11-fold increase two weeks post the booster. At the next quadrant, these are people with very low starting antibodies, and here you see a 21-fold increase in antibodies. If you look at those at the last quadrant on the right-hand side, these are people with the highest starting titers, but we still see essentially a four-fold increase against Delta. We're really seeing very, very strong boost responses to levels associated with very high levels of efficacy against COVID-19, and this is true for all variants that we've evaluated to date, namely Wuhan, Alpha, Beta, and Delta.
If you go to the next slide, obviously we're still enrolling the other two groups in the phase II study, and we'll evaluate their immune responses as they become available, and we'll be reporting the results from the entire phase II study, the different dose groups, and also the seronegatives, and the full safety profile in Q1 next year. We are continuing to gear up for phase III with maybe more energy than before. We're currently manufacturing the phase III material as we speak, and we're finalizing the discussions on the phase III design. If you remember, what we've proposed to the authorities is a non-inferiority study comparing the immune responses induced as a booster by ABNCoV2 to a comparator, which will be an approved vaccine.
As I said, those study designs have, in general, been widely accepted by the regulators. The phase III will start next year and already report out next year, while we also upscale the manufacturing activities with a view that if everything goes as we plan, we'll start filing at the end of the year, looking for an approval in the first half of 2023. Really exciting day for the development of our COVID-19 vaccine. As I said at the beginning, I don't actually think we could have expected any data that could be any stronger than what we've already seen, and it really sets up ABNCoV2 as a really great potential as a universal booster vaccine.
To change gears and talk a little bit about RSV, if you go to the slide, the RSV slide, you'll see here RSV is a blockbuster potential. We've been talking about RSV for many years. But the realization that this is a serious disease and is a huge unmet medical need becomes stronger by the year. We have an exciting RSV vaccine candidate that is based on our MVA platform encoding five different antigens of RSV. What we've shown to date is that this is a safe, well-tolerated vaccine in the elderly population, but it is able to provide very strong immune responses, both antibodies and T-cells, in the target elderly population that we're looking at.
As you'll see in the coming slides, this year we reported from a human challenge study that we were able to significantly reduce viral load following a challenge, and actually could demonstrate an efficacy at around 80% against symptomatic RSV infections. Really some of the best data that people have generated with an RSV candidate in terms of both the safety, the immunogenicity, and the efficacy. On the next slide, just to remind you, the human challenge study. This is a study that we've already reported. We vaccinated 30 subjects with our vaccine. Another 31 received placebo. Both were challenged with RSV and were monitored closely for 12 days.
The primary endpoint of the study was to see a significant reduction in viral load in the blood, but also to look at whether we could prevent RSV symptoms. On slide 16, you'll see a reminder of the results. The left-hand graph shows the significant reduction in viral load in the blood. The blue line is the vaccinated arm, and the gray is the placebo. We met the primary endpoint demonstrating that the vaccine was highly efficacious against the replication of RSV in the blood. On the right-hand side, you can see that we significantly reduced the number of symptoms following the challenge. Again, the blue being the vaccinated and the gray being the placebo.
If you combine both parameters, we could demonstrate a 79% efficacy against symptomatic RSV infections, which is really some of the best data that's been reported. On top of the immune data that we've already seen, really sets up MVA-BN RSV as a very exciting RSV candidate. Really where we are right now in terms of the competition, it is all about time to market. Every day we're delayed, we devalue this asset, and therefore it's important that we start the RSV phase III as soon as possible. If you go to slide 17, we have finalized the design with the regulators where we will enroll 20,000 subjects. 10,000 will receive the vaccine, 10,000 will receive the placebo, and we will be looking for a reduction in lower respiratory tract infections.
Between the two groups as the primary endpoints. This is a trial that will run over one season in and around the globe, both in Australia but also in the Northern Hemisphere. As I said, it will read out within one year. The overall cost of this study, due to the increase in size, is approximately $250 million. Because of that, we have announced our intent to issue new capital to raise additional funds to allow us to start this phase III and accelerate the development and time to market. With that, I think I'll hand over the rest of the presentation to Henrik Juuel.
Thank you very much, Paul. Yes, Paul, as Paul just said, I think with a decision to move RSV into phase III next year, we have already communicated our intention to raise additional capital, where the proceeds from this will go to accelerate the RSV strategy, but also to provide flexibility to pursue potential new opportunities going forward. From the annual general meeting in the spring of this year, we carry a mandate where we can raise up to 10% of our existing registered share capital, and that is the mandate that we are intending to utilize in this situation. We expect to conduct the capital raise in the near future, however, subject to the market developments. We do believe that this is the right thing to do.
With a self-funded RSV phase III trial, we can accelerate the time to market while also retaining maximum strategic flexibility in our pursuit of a partner deal. It remains our core strategy to find a commercial partner for this asset. Again, at the bottom of the slide, just to highlight the expected use of proceeds. Main part of the proceeds will go towards funding of the pivotal phase III RSV trial. We also want to use the proceeds to retain our strategic flexibility to pursue an active M&A strategy. If opportunities come by, we can act swiftly. Then also the proceeds will be used to generally strengthen the company's capital base.
On the next slide, just want to remind you of our guidance for the full year. Revenue guidance for this year is obviously not impacted by any of the announcements yesterday and today. EBITDA, however, we have made a decision-driven adjustment of the EBITDA because with the decision to move ahead with RSV, we had to spend money already this year. To the tune of approximately DKK 30 million to make sure that our CRO we work with for the phase III can set up the necessary infrastructure to conduct the trial next year. This amount was never included in our original guidance, so therefore, we are making this decision-driven adjustment of the EBITDA. Our cash position, we haven't changed that, but of course, it is subject to the potential proceeds from a planned capital raise.
Again, to the right, I think with these announcements yesterday and today, our list of milestones for the next, say, 12 months now will include some very exciting milestones, including final results from the COVID-19 phase II study. We only showed the top line data today. More will come. It will also include initiation of the phase III trial, as well as the initiation of the COVID-19 phase III. We'll expect that initial readout from COVID-19 phase III already in the second half of next year. Even though we have had exciting news coming out yesterday and today, I think, we're also building up to very exciting, news flow in the year to come. On the next slide, I think, again, just highlighting our bold vision to become one of the largest pure-play vaccines.
I just want to highlight here that with these two late-stage assets, we actually have two potential key contributors to basically deliver on this vision to become one of the largest pure-play vaccines. Quite an exciting point in time for Bavarian Nordic. I think we'll end the presentation here and ask the operator to start the Q&A session.
Thank you. As a reminder, to ask a question, you will need to press star one on your telephone. To withdraw your question, press the pound hash key. Once again, to ask a question, please press star and one. Your first question comes from the line of Thomas Bowers from Danske Bank. Please go ahead. Your line is open.
Yes. Great. Thank you very much. A couple of questions from my side. Just kicking off with the RSV phase III design. I'm just wondering, is there sort of a cap on the sample size in what you would say the pre-agreement you have with the regulators on these potential protocol amendments? If you need to, for example, add another 5,000 patients, is that just pretty straightforward, or do you need to sort of renegotiate with the FDA, for example?
On the cost side, $250 million. I'm just wondering is there any material changes to this number if you, let's say, need to add another 5,000 subjects if you have a lower incidence rates here in the southern hemisphere initially? On COVID-19. The phase III design, of course, assuming a non-inferiority randomized trial with an active booster comparison. I guess it should be pretty straightforward to use Pfizer or Moderna in a trial setting. I guess my question is there actually a risk that you will not be able to actually get that vaccine comparator into your trial?
As I guess most of these contracts are sort of restricted government contracts only. I'm just curious if you have any issues and then maybe have to go with an AstraZeneca comparator instead. And then maybe just lastly, just can you maybe just comment on the recruitment status for the 50 microgram dose and when do you expect readout? Can you come this a little bit closer than Q1? Thank you.
Yeah. Thanks, Thomas. Let's see if I remember all your questions. The first one was related to the size of the phase III and the cost. The protocol does allow us to expand the number of subjects if, for example, the rates of RSV are lower than we had originally anticipated. The way the trial is designed is that we will enroll, as I said, 20,000 subjects for the first season. If at the end of that readout the independent board believes that we've missed the endpoint because of, as I said, rates of RSV are too low, we are able, under the current protocol, to recruit more subjects in season two. It is, however, been designed with a one season in mind.
The costs that we're indicating include the cost for the entire protocol and study, including a follow-up phase and also, as I said, potentially expanding, the recruitment beyond 20,000. The other question-
Paul, can I just ask?
Yeah.
Just to be sure, so clear. The 20,000 subjects, that will be for year one, you will not have more than 20,000 for the first season. Is that correctly understood?
That is correct.
Okay, thanks.
Yeah. Then the other question you asked related to the availability of a comparative vaccine, and, you know, we've highlighted that already. You know, in the classical way of doing a non-inferiority study, you would have a randomized trial. That does involve access to a comparator. Those discussions are ongoing and different paths are being followed. However, as a backup, we're also in discussions with the authorities about if that comparator is not available in such a setting to perform the study in a different way that would allow a direct comparison between our vaccine and a comparator, for example, like Pfizer's. Those discussions are going on in parallel.
We will do the phase III, and we will show a comparison to an antibody as in that of a comparative vaccine like Pfizer's. Your last part of the question was an update on where we were with the 50 micrograms. You know, recruitment is going well, but of course we're hitting the Christmas period, so I don't wanna say too much, but we hope to report data in Q1.
Thank you. We will go to our next question, and the question comes from the line of Peter Verdult from Citi. Please go ahead. Your line is open.
Thank you. Peter Verdult, Citi. Just a few please, Paul. Just playing devil's advocate, some cynics will say Pfizer are out there with plenty of supply. When you arrive in 2023, potentially a non-inferiority study, you know, how will you differentiate? Can you just, rather than speculating, remind us, can you quantify the magnitude of confirmed orders that you have or have not from the Danish government or other governments should you receive approval? Thinking about potential differentiation, when is the earliest indication we might get with respect to efficacy against Omicron? I'm sure you're doing those assays as we speak. A cheeky add on to the first question is, you've shown data at two weeks.
Is there anything unpublished or anything you have that shows antibodies beyond that? Second question, more simple on RSV. Are you any nearer to fruitful partnership discussions since we last checked in with you at Q3? I'm only asking, given we all know on the call that the competitive landscape is pretty tough. A number of competitors are a year ahead of you. Obviously unlike the COVID vaccine, this phase III comes at risk. Anything you can say or characterize with respect to partnership discussions would be appreciated. Thank you.
Yeah. Thanks. The first question, which was multiple layers of questions actually but, on COVID. What could our competitive advantages be? Obviously, we need to generate the data, but to what I'm about to say, but I think you know, there is an urgent need for a vaccine that provides a better or broader protection against variants. You mentioned Omicron, and no one really knows where anyone is on that yet. Interestingly, with that variant, you know, there's a lot of mutations within the RBD, also with the spike protein. Four of those mutations are shared with the Beta variants. If you remember Beta, which fortunately, it didn't become a major circulating strain, but with the Beta variant, it was up to a 36-fold reduction in neutralizing titers with some approved vaccines based on RNA.
With ours, we only saw a twofold decrease, and that twofold decrease was still at a level that was very high in efficacy. I think where we sit right now is that we seem to have a very good vaccine generating very strong responses against all the major variants without the new one, obviously, because we don't have that data, which is something unique compared to the existing approved vaccines. I would hope that one of our competitive advantages is a broader protection, but also a longer-lasting protection. I think, you know, the current wave of vaccines are generating quite weak responses and need frequent boostering, or at least looks that way. I'm hoping we would be able to provide a longer-lasting protection and a broader protection. In terms of orders that we've received, we haven't received any orders.
I mean, there is a mechanism under the funding with the Danish government that we will repay in part on delivery. That is a decision for the Danish government at some point in time. You know, I would anticipate, with the data that we have that becomes more widely available, and going into phase III, we will start having discussions on pre-orders. I do not anticipate receiving pre-orders until the phase III has already read out. Your other question was on RSV and partnering discussions. You know, I think one of the decisions that we've made. We've said all along that we need a partner, but we need to start this phase III so that we don't get further and further behind the competition.
As I said, it is all about time to market, and the longer we're delayed, the less value there is on this asset, not only for our shareholders, but also for a potential partner. That's why it's important for us to make the decision, and hopefully we'll gain the support from our investors to go ahead alone initially into phase III. That takes the pressure off finding a partner, but we will continue those partnering discussions in parallel.
Thank you.
Thank you. Your next question comes from the line of Frédéric Gomez from Pharmium Securities. Please go ahead. Your line is open.
Yes. Thanks for taking my questions. I have three on the RSV and one on the COVID. Maybe we can start with the RSV. You mentioned the fact that it's important for you to start as soon as possible the phase III. GSK started in February this year a trial in the same group of patients. I'm just wondering when we could see the first patient in and how we should see the planning in this, because you want to do that in just one season. I think it's important for you to start the recruitment ahead of the next RSV season.
The second one is on the design of the phase III. I was just wondering if there is a revaccination schedule or if it's gonna be just single dose, or could we see something with a dose at M 12 or months 24, for instance, post dose one? Just a clarification on the regulatory interactions we had in the past. Can you confirm that you, of course, discussed with FDA? I was wondering if you also met the EMA scientific advice to get a phase III design fully validated by both FDA and EMA. For the COVID, the last one is you are planning a non-inferiority against an approved vaccine. Can we expect, for instance, you to mimic the design of Valneva, which decided to run a phase III against the AstraZeneca vaccine?
Are you looking for a specific vaccine or, because it may be weird, for instance, to let this choice to investigators to decide between Moderna, Pfizer or maybe AstraZeneca or Johnson & Johnson vaccine? Thank you.
Yeah, thanks for the questions. Okay, on RSV, you're asking questions about timing. You know, we're sticking to first half of next year. That would still be before typically the RSV season. However, I'd have to say this year, what we've seen is that the RSV season has sort of, it's not seasonal this year, so I'm not sure that's still relevant. Regardless, we plan to initiate the study in the first half of next year. We're looking at doing a single booster shot in the 20,000 subjects, placebo and vaccine, to try and get a readout within one season. There will be a follow-up phase where we'll follow some of those 20,000 subjects.
However, we won't wait for the follow-up to go for a regulatory filing. We're not planning on booster shots at a later time point, but there will be a follow-up with the subjects over the following season. The other question related to regulatory approvals, and we do have regulatory approvals. We have an agreement on the protocol with the FDA, as we said before, which is the main regulatory agency we've been focusing on. There has been discussions with the European authorities as well. On COVID and the comparator, I would say for us it's important to have a comparator that has been widely approved in all territories. The problem with AstraZeneca as a comparator, of course, it hasn't been approved in the U.S., which I would see as a major drawback.
We are looking for a comparator that's been approved in all the territories where we wanna focus our commercial activities. With some of the other questions already today, you know, access to any comparator is not straightforward when these vaccines are being sold directly to governments. However, I'm quite comfortable with the different strategies that we're pursuing and the support that we're getting from the regulators in their understanding of some of the challenges that we and others actually are facing in terms of doing comparator studies. Hopefully that answered everything.
Yeah. Thanks.
Thank you. Your next question comes from the line of Gil Blum from Needham & Company. Please go ahead. Your line is open.
Hi, this is Nishant Gandhi. I'm on for Gil Blum. Thank you for taking our questions. Any comment on how you think the efficacy of your vaccine will kind of hold up against the like future variants? I know it's kind of hard to tell. If you can tell me like what are the... I mean, how easy for the company it is to address like additional mutations in terms of modifying the vaccine or any changes if you have to make. Thank you.
Yeah, thanks for the question. Again, I can't comment obviously on the new variant, Omicron, because we don't have data on that yet, and I'm not sure anyone does in terms of neutralizing responses. Up until now, all the major variants of concern that we've evaluated, Wuhan, Alpha, Beta, and Delta, we've seen extremely good responses, either in a primary vaccination setting or, as we've reported today, in a booster setting. That means that ABNCoV2 rather unique in this space in that all other vaccines that I'm aware of that are either approved or in development have shown varying abilities to provide neutralizing titers against all the variants I've just said. As I said, the Beta variant, we've seen up to a 36-fold reduction in neutralizing titers by RNA-based vaccines and similarly for Adeno and other based vaccines.
Whereas we only saw a modest twofold decrease compared to Wuhan. At that level, it was still in that level that's associated with very high levels of protection. Right now we are considering that we have a vaccine that's based on the RBD that is providing broader higher titers than other existing vaccines. Of course, we are evaluating Omicron or will be, as the reagents become available, and we'll have to see where we are in that setting. One of the advantages we have with our platform, not only does it generate strong immune responses, but we have as a backup already begun to create a new construct that could be specific for Omicron, just in case.
It does look like a variant with a lot of mutations in the spike protein and in the RBD, so we'll have to see where the data is. We have, as a precaution, already started a new construct. I would say in terms of how quick we can be, I don't think we'd be any slower than the RNA-based technologies in generating the new construct.
Great. Thank you.
Thank you. Your next question comes from the line of Michael Novod from Nordea. Please go ahead. Your line is open.
Yeah, thanks a lot. It's Michael from Nordea. Just two small follow-up questions again to the Omicron. Is there any sort of more specific timing also to Pete's question, when you could have any data available, just so we get some timing straight on terms of knowing whether you need to do a modified vaccine construct towards Omicron? And then secondly, also to that, do you have any risk that you would have to run clinical trials against other modified vaccine constructs? Because we have Moderna, BioNTech, and others working on Omicron-specific vaccines. Just try to highlight the risk that we need to do sort of clinical trials in a different setting to what is already in the plan now.
Yeah. Thanks, Michael. So in terms of timing, again, I'm gonna fudge the answer a little bit because it's a bit uncertain. One of the assays I talked about was this competitive receptor binding assay that we generated the data for Delta. Hopefully, we will get access to that commercial kit shortly. I say shortly, hopefully before the end of the year. And that would allow us to run the samples. We're also making the pseudovirus, but I think that will take a little longer. I'm hopeful that we will have an indication in the coming weeks. But that means, you know, coming weeks could mean that we're pushed into January. In terms of the risks for the phase III. Now, of course, if, you know, various scenarios, right?
If Omicron becomes the major variant, obviously that's the variant that is of major concern, and that's the one that we'll have to be focusing on. Let's, for example, say that we use an RNA vaccine as a comparator. If the current vaccine is not effective against Omicron, then the comparator will have to be an Omicron specific comparator. That's just the way it will be. That's how the world is going to change if this variant is actually escaping the current immune responses. As I said, let's see whether we do need to change our construct. I'm still... Yo u know, based on the data that we generated today, and particularly for Beta, as I said, which shares four of the mutations with Omicron, I think we're hopeful that we won't and that we're still in a good position.
As a precautionary backup, we have already begun generating a new construct. We'll just have to see how the data pans out in the coming weeks.
Okay, thanks.
Thank you.
Thanks a lot.
Thank you. Your next question comes from the line of Peter Welford from Jefferies. Please go ahead. Your line is open.
Hi. Thank you. I've got four questions left, one on RSV, first of all. I guess the question really is why 20,000 in the first place? I think some of your peer trials are already using larger populations than that. Is cost a factor here, or is it more just your analysis based on your efficacy from the human challenge? And I guess what's limiting the decision not to, in the first place, recruit more to potentially get a more rapid readout, given, as you said, time to market is key. Then just three on the COVID vaccine.
Firstly, just on the 50 microgram dose booster, what sort of potential fold increase or lower fold increase, I guess, would we need to see with that dose for you to decide it would be beneficial to move that forward into phase III? I guess what I'm asking is, based on what you see now, you know, what's the hurdle for the 50 microgram to decide that that's actually a preferred option? Secondly then, speaking as someone who's had an mRNA booster and knows what it feels like, can you talk a little bit about the injection site reactions and the sort of tolerability of this in the study, and whether or not you do think, sorry, that over time could potentially become a factor for boosters.
Finally, when you do the manufacturing, are you scaling up manufacturing on the basis of potentially likely to ship in 2024? I say that just because even though, you know, you could be available, you said to launch in 2023, I think, you know, the majority of 2022 and 2023 orders and need in the world is probably already met by existing capacity at the moment. Are you scaling up really more from a 2024 timeframe? Thank you.
Yeah. Thanks, Peter. The first question was the size of the trial and why is it not larger compared to some of the competition. I mean, again, I don't wanna comment too much on the competition. They do their thing. We believe that with the current rates of RSV that we're seeing, 20,000 subjects is sufficient to meet the endpoint. From our statistical analysis, that is gonna be sufficient. As I said, there is some flexibility in the protocol that should the rates of RSV be lower than we thought, we are allowed to expand the enrollment. One thing I would say about the competition is, of course, when they started their studies earlier this year, that was on the back of very low rates of RSV.
They may have been very cautious, probably rightly so, in terms of their estimates of what the rates of RSV were going to be this year. We're obviously seeing what the rates actually are and designing the study based on that. You had some questions on COVID. The hurdle for the 50 micrograms, that's a good question, to be honest. I think there's two things in there. One is, you know, I think we've got some great data. Would we compromise by seeing slightly lower immune responses for a lower dose?
I think one of the things that we need to be very cautionary about and evaluate further is the comparative vaccine and the absolute levels that we're seeing with a potential comparator and ensure that we are able to show non-inferiority. Based on the 100 microgram data that we've reported today, we are very confident and comfortable in showing non-inferiority with the data that I've seen reported for other potential comparative vaccines. The safety profile, you know, I didn't show any data on the safety because the trial is still ongoing. We haven't locked the database and the like. What I would say is it's still well tolerated. We've seen no serious adverse events. However, I would say that the local and systemic reactogenicity is slightly higher than we saw in the primary vaccination setting, where we really didn't see any real signals.
Here, we're seeing the usual site reactions in terms of redness, swelling, pain. Most of that is extremely well-tolerated, but I would say the reactogenicity is slightly higher than we saw in phase I. That's probably expected because we are in a booster setting, and the body is already well-primed to the antigen that we're delivering. As I said, let us wait until all the data's in before we start sharing the safety data. In terms of manufacturing, you said are we gearing up for 2023 or 2024. I think in all essence, you know, our initial capacity is looking at a 2023. Having said that's because we would be anticipating some advanced orders before we launch.
This is a very unusual market where you wouldn't launch and then, you know, have your marketing activities to get sales. We believe there could be some significant sales prior to actually filing, and launching this product.
That's great. Thank you.
Thank you. Your next question comes from the line of Jesper Ilsøe from Carnegie. Please go ahead, your line is open.
Thank you. Just a question on the long-lasting duration you have with the ABNCoV2. My question basically is, I know VLP technology in general has long duration like Merck's Gardasil. Do you expect similar, say, years of protection, or do you see this as a different virus that perhaps has, as you know, fewer years of protection? Basically, what's your base case given the data, the indications you have to date, how many years of protection do you think you could actually have with ABNCoV2? And then I have a question on RSV. Just for modeling purposes, you perhaps answered it a bit with Thomas' questions, but just the, say, potential split of R&D costs in 2022 and 2023. Just any high-level expectations you can provide? Thank you.
Yeah. Hi, Jesper. The length of protection is an interesting question because currently the first wave of vaccines don't seem to be inducing very long-lived protection. In fact, very short levels of protection with a booster being required after six months. The question really is that due to the virus in terms of SARS-CoV-2, or is that due to the vaccines? Because as I said, six months protection is really rather unique in the vaccine space. Now, for adenoviral-based vaccines, we know they don't induce long-term memory, so that fits in. We obviously with RNA, it's a new technology, and we don't know whether it's suffering from not inducing a good memory, or, as I said, whether it's something specific about this particular virus that makes it difficult to give you a memory response.
Again, however, if you look on the more optimistic side, you mentioned it yourself, the virus-like particle technology is renowned for giving you long-lived responses. I think we have the ideal platform to generate better protective longevity than the current wave of vaccines. And I think the bar is very low. At the moment, it's six months. I'm hoping that it's gonna be several years. You know, we have to generate the data before I can really start, you know, speculating on what it will be. I hope we can beat six months because there is a need. I mean, if you need a booster every six months, this is a very unusual vaccine setting. Yeah, I hope we can do better.
I think we will be able to do better based on the data we already have in terms of the magnitude, but we do have to generate that data. On the RSV, maybe, Henrik, do you wanna take that?
Sorry.
Breakdown of R&D costs, I think was the question.
Yeah. On R3, I think what we have indicated is that we expect that the phase III will cost up to $250 million, but that includes follow-on phases happening in 2023 and 2024. As Paul said, also, there's room there for potential expansion should the incidence rates be low. We are also going to spend money on, you could say, process development, scale-up for manufacturing, et cetera, but that's sort of within our existing budgets normally for R&D. Here we have chosen to be specific on the clinical development costs up to $250 million.
Okay. Thank you. Just one more question on COVID-19. Henrik, you're also out in the media reports saying that since you will start phase III here H1 2022, that's also the time you can start going to dialogue on potential orders with authorities and governments. Given that you potentially not will have, say, proof that you have a longer-lasting vaccine, what do you see as the most important element or advantage when starting negotiations with the governments and authorities? What is the real, say, trigger choosing you versus other vaccines? Is it safety? Is it the broader protection or anything particular that you see as the best advantage?
I think we need to provide some good clinical data. In the first instance, that will come from our phase II, of course, where we have already presented some really attractive data. Of course, we need to complete that study, get the rest of the data. Of course, I think the clinical data in relation to performance against Omicron will be important, et cetera. I think in terms of timing, when we can have that dialogue with governments, I think we have had the dialogue already now and then. That is to keep them aware of our vaccine candidate.
I think those could become much more concrete and specific once we are past all the phase II data and we have sort of, I would say, started the phase III, so that there, as you can see, the light at the end of the tunnel with respect to finalizing the clinical development, basically.
Thank you so much for taking my questions.
Welcome.
Thank you. Oh, thank you. As a reminder, if you'd like to ask a question, please press star and one. Your next question comes from the line of Suzanne van Voorthuizen from SEB. Please go ahead. Oh, Suzanne has just withdrawn her question. I do apologize. Oh, Suzanne is back. Let me just open Suzanne's line. Suzanne van Voorthuizen from Van Lanschot Kempen, your line is open.
Hi, guys. Sorry, something went not terribly well. Thanks for taking my question. First on COVID, and then also I have a follow-up on RSV. First, the COVID phase III booster study regarding the non-inferiority against an approved vaccine seems like you really want that one way or the other. I'm just wondering, is there a scenario possible that you will be running a trial without a comparison to an mRNA vaccine, but for example, you would purely be looking at boosting versus baseline? And maybe it sounds crazy, but could the Danish government support that you have perhaps play a role in accessing the Pfizer vaccine for phase III purposes?
Yeah, thanks. Yeah, as I said, if you go from what is the ideal study from a regulator's point of view, it's a randomized controlled study where you'd have two arms, and they like the randomized blinded part to avoid any bias in one arm or the other. That's the ideal. But for that, as we've been discussing, we really need access, physical access to the comparative vaccine, which may be difficult. Having said that, we are in discussions with a number of different regulators and bodies, one of which actually is the Danish government in a way of potentially supporting such a study. Some of the other backup solutions that we're looking at and are in discussions with the regulators is how would we do such a study?
Is there a compromise, if we don't have physical access to the comparator? One way that we're investigating as a backup is actually to be in tandem with a government program, a government booster program where we would get access to individuals going into a government program who would be receiving their booster. That's not as tight from a regulatory point of view in terms of randomization, but those are some of the discussions that we're having. We haven't been as creative just to see whether we can see a significant boost on baseline. I think from the initial discussions we've had with regulators, that wouldn't be acceptable. They want one way or another to see a comparator. Again, you know, regulators can't ask a company to do something that is impossible.
The onus of finding a solution is also with the regulators as well as it obviously lies with industry as well.
Got it. Okay. No, that's very helpful. Then, maybe on RSV, and I'm just wondering if there's more or less an ultimatum for the planned capital raise in order for you to meet the timeline of starting the phase II next year. Because it seems like this may cause a bit of an overhang on the shares. I'm wondering, by when this should be clarified. You mentioned RSV is not really that seasonal anymore. Perhaps you can elaborate on that and provide some color on how COVID changed the incidence of RSV.
Perhaps I can first comment on the capital raise. I think it is our intention to get that done as soon as possible. That means in the very near future. But of course, still subject to how the market is developing. But there's no doubt that we want to conduct this also as soon as possible so we can get any potential overhang out of this year. On the seasonality of RSV, as I'm sure you're aware, RSV follows the same sort of season as flu and other cold-like diseases. What we've seen this year is RSV outbreaks. Overall, the rates of RSV are increasing compared to what we saw the year before when obviously everyone was socially distancing and in lockdown.
However, what's unusual this year is that we've seen pockets of quite high levels of RSV during the summer months, during the late spring and summer months where you normally don't see high levels of RSV. Will that continue into next year? No one knows. Or will it return back to a more seasonal disease? Again, no one really knows. How we've modeled RSV for the phase III is basically just on the total number of on the infection rates. As I said, we're going during the first half of the year. We will be in time for the normal season. If it's not seasonal anymore, then the rates of RSV, you know, we're taking that into account in terms of the overall rates of RSV.
Got it. Thanks a lot, and congrats on the data.
Thank you.
Thank you. There are no further questions at this time. I will hand back for closing remarks.
Thank you everyone for taking the time to join the call and for all the questions and interest that you've shown today. Thank you, and have a great day.
Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.