Thank you, operator, and good morning to some, and good afternoon to the rest. Before we start the presentation that will be conducted by President and CEO Paul Chaplin and Executive Vice President and CFO Henrik Juuel, I would like to read the following statements in our disclaimer. 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 from the results discussed.
Forward-looking statements include statements regarding our short-term objectives and opportunities, financial expectations for the full year, and financial preparedness as of year-end, as well as statements concerning plans, objectives, source, 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 this, I will hand it over to you, Paul.
Yes. Thank you, Rolf, welcome everyone to our Q1 update. If you go to Slide 3, Bavarian Nordic is a fully integrated vaccine company, and at the beginning of last year, we set ourselves a new vision to become one of the largest pure-play vaccine companies by 2025. Within just one year, we have really made huge progress towards that vision and in the execution of our strategy.
We've greatly expanded with a number of employees to more than 700 currently, and that's to help produce, distribute, and sell our commercial portfolio of vaccines, where we have currently four products around the world. We have built up a commercial infrastructure in key markets, which allows us to sell and distribute these products. Importantly, we are continuing to expand and build on our expertise of commercial manufacturing here in Denmark.
Added to that, we have a rather exciting R&D pipeline with two near-term assets. We have an RSV late-stage program that's currently in a human challenge study with data coming later this year. We have a COVID-19 vaccine which we're developing as a universal booster vaccine, hopefully providing a more durable and broader protection than the current first wave of vaccines.
Really some exciting times and data points coming in the next few months. Added with all of that, we have our strong ambition to remain a profitable company, and using those profits to develop more products in the pipeline, which we'll add later to our commercial portfolio. If you turn to Slide 4, as I've just said, we have a vision to become one of the largest pure-play vaccine companies, but we also recognize the importance of protecting and taking care of the world around us, and to act in a responsible way in all matters.
Being a vaccine company, however, we are ideally positioned to play an important role in ESG. Vaccines have become extremely topical in the last few months due to COVID-19 with the rollout, and it's clear that vaccines are the really only hope we have of the world coming out of lockdowns and getting back to normal. However, vaccines have played an important role for more than the last 200 years and have really improved the world's health. As you can see from the quote from Gavi, 14 of the 17 strategic goals can be achieved through vaccines.
As I said, we are very well- positioned to play an important role, and obviously, our investors and stakeholders hopefully will join us in that journey. If you'd like more information on our work on ESG, you can see that in the CSR report that's available on our website. Turning to Slide 5. We've had an extremely busy and productive Q1.
While we still face some rather strong headwinds for our rabies franchise due to COVID and the travel restrictions, I'm sure Henrik will come to that in the coming slides, we are seeing some signs of stability on tick-borne encephalitis despite COVID. Similar to last year, our smallpox contracts, both with the U.S. but also with new orders from E.U. countries, have allowed us to record larger revenues in Q1.
That leaves us with the confidence that we maintain our full-year guidance that we set a few weeks ago. You'll have heard the news this morning, and I'll come back to that in the coming slides, that we're expanding our portfolio of commercial products in Germany with a collaboration to market and distribute Dynavax's innovative Hep B vaccine. I'll come back to that in the later slides, but that is a very exciting development, considering that we've only set up our commercial enterprise in Germany nine months ago.
If we look at some of the orders, as I said, it's interesting that we're starting to see an expansion of orders outside of the U.S. for JYNNEOS, that's smallpox vaccine, both in Europe and also in Canada. As I've said, that's allowed us to record slightly higher revenues in Q1, and Canada will probably be revenue recognized next year. The U.S. government continues to honor its options of the order that was placed a few years ago with another $12 million exercise of an option. On Ebola, we've seen some exciting news, where together with our partner, Janssen, we're going to manufacture additional doses, which will help be distributed and help with the current outbreak in Central and Western Africa.
We've also announced the news that our vaccine is WHO pre-qualified, which will allow an easier distribution of these vaccines in areas that are desperately needing an Ebola vaccine in the current outbreak. On R&D, and I'll come back to this in the coming slides, we've probably seen the best preclinical data of any COVID-19 vaccine candidates, and I'll walk you through that.
The phase I data from our partners, with AdaptVac and ExpreS2ion and their EU consortium, the early data is confirming that very strong preclinical data. We're about to initiate a phase II study, which I'll come back to. On RFPs, as I said, we're halfway through a human challenge study, where we'll be reporting data from that exciting study later this year.
If we turn to Slide 6. As I said this morning, we made an important announcement that we've come to an agreement with Dynavax, where we will market and distribute their highly innovative two-dose vaccine against hepatitis B, HEPLISAV-B. That will be launched in Germany later this year. This will break the current E.U. monopoly, which is currently valued about DKK 27 million annually.
As you'll see on the right part of that slide, this next year will add to a very strong portfolio of commercial assets that we'll have in the largest E.U. market. As I said, if you just go back nine months, we had no commercial presence in Germany. Within that nine-month period, we're very proud to announce that Dynavax has approached Bavarian Nordic as the ideal company to distribute and market their innovative vaccine, which has an advantage over the current vaccine in that it's a two-shot vaccine, providing a very strong efficacy within four months.
Within one month, sorry, versus the three-shot regime that's currently been around for a number of years, that takes six months to complete. As I said, this will add to a very strong portfolio we already have in the largest E.U. market. Slide 7. COVID-19, and one of the questions I often get is, aren't you a little late? Why are you developing a COVID vaccine when most of the world, particularly in Europe and the U.S., is already vaccinated or will be shortly?
There's a couple of issues with the first-wave vaccines. Thank God they're here, and we can all get protected from COVID-19. The durability and the breadth of protection that they provide is a little unclear. We don't know how long they last or whether they truly protect against some of the more serious variants that are emerging. I'll come back to that in the coming slides.
It is unlikely, or most people in the community believe that COVID-19 can be eliminated through vaccination, and it's likely, just like other infectious diseases, that we'll have to manage the burden of disease through vaccination, and frequent or additional boosters are going to be required. Obviously, the bottlenecks that we've experienced in the last six months have highlighted the need that more vaccines are required, more vaccine manufacturers are required to meet the current demand.
Lastly, the first wave of vaccines, there's a lot of question marks whether they are really truly suitable as booster vaccines. Two of the first-wave vaccines are based on an adenoviral vaccine platform. It is known from the literature that they suffer from a pre-existing immunity generated to the viral vector itself, which may make frequent boosting difficult or impossible, or certainly reduce their efficacy.
With RNA, there is now growing concerns that there are quite some Grade 3 systemic adverse reactions that are increasing with additional boosters. Some data that Moderna have published, the Grade 3 AEs or adverse reactions, systemic adverse reactions, were at 2.7% in the first vaccination, going up to 9.7% after the second. In their booster study, which they've reported, it's almost 15%. Clearly increasing after shot, after shot, after shot. That raises questions, is this platform really the ideal platform for regular boosters?
From our position, with everything I've just said, there is room and a need for improved vaccines, both from a safety perspective, a durability perspective, and a breadth of protection perspective. If we go to Slide 8, as I said, we've probably published some of the strongest preclinical data for any COVID-19 vaccine, and I will go through that in the next slide.
Our platform, which is based on a VLP or viral-like particle platform, is relatively easy to produce and/or adapt should there be a need to adapt the vaccine for new variants, should there be further mutations beyond what we're already seeing. As I said, our partners and the E.U. consortium are already in phase I, where we're beginning to see some data confirming the preclinical data.
Within a matter of weeks, we'll be starting a phase II study, while we're also in parallel gearing up production to potentially start a phase III should we be able to secure funding in the coming weeks and months. If we turn to Slide 9, I keep talking about the best preclinical data, so let's talk about it.
On the left-hand side is the neutralizing titers that are induced in primates following two shots of a non-adjuvanted ABNCoV2, which is our COVID-19 vaccine candidate. It's known from the literature that the level of neutralizing antibodies is predictive of the final efficacy that you may see in the clinic, and that is by comparing to convalescent human serum. Many publications are saying that your clinical efficacy should be greater than 80% if you have a ratio of one or greater to the human convalescent serum.
You can see in primates, we have a 50-fold higher neutralizing titers with our vaccination compared to the high convalescent sera, which bodes well to predicting a high efficacy in the clinic, which of course, still needs to be tested. In these animals, there was complete protection following a challenge with SARS-CoV-2, which again bodes well for strong efficacy in the clinic.
On the right-hand side is some additional neutralizing data where we've looked at the sera from the primates and their ability to neutralize new variants. Well, some of them are quite old variants. Wuhan is the main strain that obviously emerged from China and is equivalent to the data on the left-hand side of the graph. The middle is the British variant, which, as you know, was shown to be more infectious in the U.K.
On the far last column is the South African variant, which is causing issues around the world. What we see is that we see exactly the same neutralizing titers, 50 x higher than human convalescent sera, and no difference between the variants and the Wuhan strain. This is not the same data that others have published for current approved vaccines. For example, in a publication, the Pfizer-BioNTech data show that there's almost a threefold lower neutralizing titer against the South African variant.
The Janssen vaccine actually reported 74%, if I'm correct, efficacy in the U.S., which is primarily, at that time, Wuhan, and only a 57% efficacy in South Africa. Again, a reduced efficacy probably associated with a lower neutralizing titer. These data really bode well that our vaccine, by generating such high neutralizing titers, is going to give a broader protection against the current circulating variants than the existing approved vaccines. Slide 10. As I said, we have phase I trial ongoing, sponsored by our partners and the E.U. consortium.
They've already reported preliminary data showing that the vaccine is extremely well-tolerated, particularly in its non-adjuvanted form, and induces high levels of neutralizing antibodies, again, supporting the preclinical data that I've just shown you. In June, just a few weeks away, we'll be initiating a phase II study, which is shown in the bottom half of this slide. It will be essentially two groups. One group will be seronegative, i.e., not previously vaccinated or infected, and they will be receiving a primary vaccination regime of two vaccinations, four weeks apart.
Group two will all be seropositive, so previously vaccinated, and these will receive a single booster with our ABNCoV2 candidate, which is how we believe we'll be developing the vaccine primarily in Europe and the U.S. This will lead to data that we will be reporting mid of this year.
Changing tracks a little bit, moving to Slide 11, talking a little bit about RSV. As you are all probably aware, we announced at the end of last year, we were delaying the initiation of our phase III due to the low infection rates of RSV caused by the shutdowns and the social distancing and all the other measures associated with COVID-19. We are, however, doing a human challenge, which is currently being conducted, and we will be able to report the data from this study later this year.
That will hopefully give us added confidence that we are truly looking at a highly efficacious vaccine. That will hopefully allow us to initiate a phase III study next year. On Slide 12, we've been investing quite heavily in our manufacturing plant, adding a fill-finish capability, state-of-the-art fill-finish manufacturing, which is now complete. We are actually in the process of transferring a number of products to the line.
The liquid-frozen formulation of JYNNEOS is very advanced, and we should be validating that process in the coming weeks. We've already initiated the first engineering runs also for the freeze-dried version of JYNNEOS, and I'm pleased to announce that we've also initiated the first engineering runs for Rabipur, really indicating that our tech transfer activities from GSK remain completely on track.
In addition to that, we're expanding our bulk facility to allow us to produce the bulk for both Rabipur and IMVAMUNE. That is going extremely well, on track, on budget. Later this year, we will be shutting down our bulk facility as we start to reconnect both the expansion part that is ongoing right now with the existing building one as we call it, where we've currently been manufacturing our smallpox vaccine.
As planned, there will be a shutdown of the bulk manufacturing, but as I said, that's all part of the plans. When we've finished all this work, we truly believe we're creating a center of excellence for vaccine manufacturing based on CEF cells . As I said, highly productive Q1. A lot happening, and there'll be a lot more news flow coming in the coming months. With that, I will hand over the presentation to Henrik.
Thank you very much, Paul. On Slide 13, we will start the presentation of the financial results. Before we move into the hardcore financial numbers, let's have a look at the performance and the market development for our two vaccines, the rabies, our Rabipur product, and our TBE vaccine, Encepur, in these markets. On Slide 13, it's all about our rabies business. As we have preached many times now, I think when we look at the rabies market, I think we have to distinguish between the U.S. market and the German market, as they are very different markets.
If we start with the German market, which is at the bottom of the slide to the left, you will see that the German market has since first quarter 2020 declined by more than 90%. This is due to the fact that the German market is nearly 100% a pre-exposure market, meaning a traveler's market. Rabies is not endemic in Germany, the market here is really a traveler's market where people vaccinate when they go to relevant countries.
The situation is that there's nearly nothing left in the German market at the moment. We are, of course, awaiting travel patterns returning to normality, and then we expect the market to come back full force again. I think what's worth mentioning here is that when we are comparing to the first quarter 2020, we are comparing to a period just before the COVID-19 situation really started last year. 91% down at the German market, and which is a good proxy for other European rabies markets, unfortunately.
If you look at the U.S. market, this is a very different story because the U.S. market consists of both a post-exposure and a pre-exposure market, as rabies is endemic in the U.S. market, which makes it a much more resilient market to the COVID-19 situation. However, that said, we are still seeing a decline in the U.S., with the market being down 21% first quarter this year compared to prior year. How have we performed under these conditions? We can see that to the right side of the slide here, we delivered total revenue of DKK 80 million for the first quarter against DKK 218 million last year.
A decline of 63%, explained primarily by the COVID-19 impact, but also by the fact that last year, the first quarter before COVID broke out, we had an extremely strong first quarter as we also faced a situation with our competitor being out of stock. Adding to that, also wholesalers stocking up to ensure that we could safely deliver into the market. We are comparing against a very strong first quarter, but we also feeling the impact of the pre-exposure segment, both U.S. and Europe, being significantly down.
I think the good key message to take away here is that our market share is still performing well. We have in the U.S. today approximately 73% of the market. We did lose some percentage points as our competitor came back in the fourth quarter last year, but that was fully expected naturally. We are happy to say today that even today we have 5%-6% higher than the average share in 2019 before we took over the responsibility, of course, for this Rabies business.
A strong position, and we are well-positioned to grab the market when it comes back and travel resumes again. On Slide 14, let's have a look at the TBE, tick-borne encephalitis market, which is a pure European business. Here we have shown the German market as an example for how things are looking in Europe. We do not yet have the full consolidated market data for all of Europe. The indications we get that the total market in Europe is down in the first quarter compared to last year due to COVID, but actually with Germany being the exception.
We have seen in the first quarter of 2021 an 8%, nearly an 8% growth compared to the same quarter last year, which is a good sign that things are returning to some more normal situations in the German market. The demand for TBE vaccines as such should not at all be impacted by the COVID-19 situation. Of course, the access to your physicians, et cetera, has shown to impact the total market.
With an 8% growth right now, I think that is a good sign for the current vaccination season. If you look to the right, you will see our numbers. We delivered revenue of DKK 98 million for the first quarter against DKK 103 million last year, so 5% down. This is caused by the total combined European market being somewhat down, with Germany being the exception, of course. Then it is also due to some inventory movements at the wholesalers.
Again, key good takeaway here is that we have actually, since we took over, gained market share with our TBE business. In Germany, I think we have gained year- to- date this year 0.3 percentage point market share. Again, very well- positioned to grab the market when it comes back in Europe. Hopefully, I think what we are seeing in the first quarter is just Germany leading the way. Next Slide 15 shows our profit and loss for the first quarter, where we delivered a strong top line with DKK 535 million krona of revenue, driven by strong smallpox revenue. DKK 336 million was actually coming out of the smallpox business, as you can see the donut chart to the right.
DKK 246 million of that was revenue for products BDS batches delivered to BARDA as part of the $202 million order that we got last year. The other part, DKK 90 million krona, is related to the three European countries to whom we have supplied smallpox vaccines as well. This is a little more than the EUR 11 million that we announced previously and simply due to somewhat better pricing terms.
You can see the two products we already talked about, Encepur coming in the DKK 98 million krona revenue, and Rabipur, DKK 80 million krona revenue. Finally, a small piece of contract work coming from BARDA funding of our phase III study and qualification of some of the work going on with our fill-finish facility. Production costs came in at DKK 377 million krona, which gave us gross profit of DKK 158 million krona.
R&D added up to DKK 122 million krona, nearly twice as high as the level we saw in first quarter of 2020, driven by RSV in the first quarter here. We have, during the first quarter, manufactured all the material that we will need for a planned phase III trial for RSV. We have also started the human challenge trial. Quite a lot of money has actually been spent on the RSV projects. This RSV manufacturing has actually also impacted our production cost for the first quarter as we are using our commercial facilities also to produce clinical material. Of course, we allocate costs to those R&D projects, and a lot of that has gone into the R&D line.
We are not allocating this on 100% basis, meaning there is some infrastructure costs, et cetera, which is not being absorbed by commercial products when you manufacture for R&D. There is also a negative impact on production costs for the first quarter due to the manufacturing of the RSV material. SG&A costs came in at DKK 124 million krona, more or less at the same level as we saw in the first quarter of 2020, but with several moving parts underneath that.
We have seen, for instance, on distribution, a significant saving as we have moved away from the GSK distribution network and now established it at home. On the other hand, we also had, particularly on admin, relatively low level of admin costs in first quarter of 2020 as we were only starting up or ramping up the integration project for the Encepur, Rabipur products integrations.
All in all, adding that together, SG&A costs slightly below the level we saw in prior year. All of this together gives us an EBIT for the first quarter of DKK - 88 million krona. Deducting the depreciation and amortization or adding these back gives us an EBITDA for the quarter of DKK 1 billion krona. I think with this situation, again, strong revenue driven by our smallpox business this time. We had gross profit and OpEx impacted by the RSV and manufacturing of phase III material in particular. We still had a positive EBITDA. With this, I think we are in a position where we can maintain our revenue and EBITDA guidance.
Turning to Slide 16. Quick update on our cash flow and balance sheet. If you look at the cash flow table to the left, we delivered net cash flow for a period of DKK -43 million. This was, of course, driven by a negative net profit for the period and/or was strongly supported by the proceeds from the private placement that we did, raising approximately DKK 1.1 billion krona.
Cash flow from investment activities reduced, of course, cash flow for a period by nearly DKK 1.1 billion. Most of that was really related to placing of the liquidity in securities, but also some of it, approximately DKK 100 million krona, was related to the continued investments in our property and continued investments in our tech transfer plans. To the right, just a few selected balance sheet figures. I will just mention the equity here.
We have seen an increase to now nearly DKK 6 billion krona, and of course, positively impacted by the recent private placement we did. I think after the quarter and after this private placement, we had a very, very strong cash position of nearly DKK 2.6 billion krona, allowing us the flexibility to move ahead with our strategy and honor our obligations to GSK during the next periods. With this numbers on this slide here, happy to say again that we can also maintain our cash guidance for the full year. On the next slide, to the left, we have an overview of our 2021 financial outlook and guidance.
As I said, we are maintaining this guidance on all aspects, both on the top line, where we are guiding a level of DKK 1.9 billion krona -DKK 2.2 billion krona, and EBITDA of DKK 100 million krona- DKK 250 million krona, and the cash position of between DKK 1.4 billion krona and DKK 1.6 billion krona. We are still seeing some uncertainties in the market, and we haven't seen the reopening as we had hoped for earlier this year.
Therefore, we still stick to this way of guiding with using intervals. Of course, we do hope that we get some more clarity on the market situation for the rest of this year during the next quarter here, so that we can come out with, hopefully, a more precise guidance in connection with our Q2 report later.
As we have said previously, I think, of course, the low end of the guidance really reflects a delayed reopening, whereas the upper end really reflects that we should see the reopening happening now, basically, with an effect that could mean already some traveling starting to occur later this year. We've also previously said that the smallpox and Ebola business are not expected to be impacted by COVID-19. That's still the case.
As you will have seen, we did announce the additional Ebola order, $28 million recently. We announced that, and we stated that there would be no impact on our guidance from this, as we had to agree with all the customers to defer delivery of some of their products into next year. Finally, on the right-hand side of this slide here, just a brief overview of what are the key activities and priorities for the remaining part of 2021. Within R&D, of course, we have some very exciting period ahead of us in terms of the human challenge trial, where we expect to have read out in September.
We will continue to prepare ourselves for an initiation of a phase III trial next year on RSV, of course, also continue to be monitoring the market to see what is the prevalence of RSV, how feasible do we assess that it is to conduct a phase III given the COVID-19 situation. Of course, also a lot of resources are put behind our COVID-19 vaccine candidate, which we are, as Paul said, accelerating into phase II within a couple of weeks.
In parallel to that, we are working to scale up manufacturing so that we can produce volumes at phase III levels. I think finally on R&D, I can mention also that we are continuing to work with our new construct MVA-BN intravenous administration of Brachyury will continue throughout this year. On the commercial side, of course, this is still to continue to drive the profitable growth. The key activity will be to take over the remaining countries in terms of marketing authorizations and distribution. We are nearly there, and actually expect that by the end of June, we have taken over all markets.
One activity that we can now add to the list on commercial is, of course, now we know we have HEPLISAV on board from Dynavax, and a key activity will be to have a successful launch for this product in the fourth quarter of this year. On the manufacturing side, the fill-finish facility is up and running. Construction complete, qualification nearly complete.
This year, we will pass a very important milestone as we will fill the first commercial product on the line. Of course, on manufacturing, I think it's all about staying on the right path and complete the construction that we need, the amendments we need to the bulk facility to transfer manufacturing of the Rabies and TBE products. Then, of course, continue to stay on plan on the tech transfer of these products as well. With that, I will give the word back to the operator for question and answers, please.
Thank you, sir. As a reminder, to ask a question, you need to press star one on your telephone. To withdraw your question, please press the pound key. Once again, please press star one for a question. Sir, your first question comes from the line of Michael Novod from Nordea Equities. Please go ahead, your line is open.
Thank you very much. This is Michael from Nordea in Copenhagen. Three questions, please. First of all, the preliminary data you've seen out of the first phase I trial with ABNCoV2, can you probably detail a bit more on that? Is it for the low-dose cohorts? I would assume it is. Just maybe try to explain what you're actually seeing in terms of neutralizing antibodies. Secondly, I know it's very difficult to comment on these sort of funding discussions. Is it still the belief that the most likely funding should come from government funding, or do you also still pursue other avenues regarding funding for ABNCoV2?
Lastly, on the manufacturing temporary shutdown you're doing according to plan, maybe if you could just talk a bit about the structure of this, whether it would have any implications, whether you are manufacturing in advance to meet demand, et cetera, just to get a bit more light on the potential impact from this?
Thanks, Michael. The preliminary data from the phase I is we're using the lower doses. If you remember, our partners are looking at both non-adjuvanted and adjuvanted vaccine. The main conclusions from the study, apart from the fact it's well-tolerated, is that the tolerability is better with non-adjuvanted, which is exactly what you'd expect. Not that it's bad with the adjuvant, it is improved without the adjuvant.
Lastly, in terms of the immune response, it's kind of in line with what we're seeing from preclinical. We're seeing superior titers compared to human convalescent sera, even at the very low doses. The dose that we're going to move forward with is much higher. They're now moving to the slightly higher doses in that trial. Really encouraging. It looks pretty good.
Terms of funding, I think at this stage it's safe to say that we are following a number of different tracks still. There is what's out there in the public in terms of the open discussions that we're having currently with the Danish government. That's public, so I can mention that. We're also looking at other funding, CEPI and whatever, but that's more early stages. I think nothing's really changed since the last time we talked.
We're talking to governments, and we're looking for funding from the usual sources. In terms of manufacturing, our main goal right now is to scale up and manufacture to supply phase III. We are, however, beginning to prepare for commercial production. Again, as we've said before, the commercial production piece really requires additional funding, also for the phase III. Of course, we're not sitting on our hands doing nothing until we get funding, but the bulk of that activity really needs to wait for funding.
Yeah. Michael, I think you had a question on the announced manufacturing shutdown as well. Maybe I can take that one.
Yeah.
This is a planned shutdown, something we wanted to highlight here as well, because of course it has implications. As it is long planned, I think we have also planned the manufacturing schedules around it. For instance, we now manufacture all the Ebola batches that we need to deliver under the latest order to Janssen.
We managed to get all the RSV materials, phase III material, manufactured before we do this plant shutdown. It's simply a necessary thing to do to connect the two new buildings or the new building to the old one, once the new one has been constructed. Of course, it is something that you don't want to drag on for too long. It does impact your flexibility to manufacture bulk in this facility, and it does impact your finances when you're not manufacturing commercial products in this facility. As I said, it's all planned, and it's factored into our guidance for this year, so there's no additional impact.
I think one thing that will help us offset a negative impact of having sort of idle capacity in some quarters will be that we are actually, for the first time this year, we are going to use our fill-finish facility for commercial manufacturing. You can see there, we start having the opposite situation. For the first time, actually using one of our facilities for commercial use.
Okay, thanks a lot.
Sir, your next question comes from the line of Boris Peaker from Cowen. Please go ahead.
Great. My first question is on the COVID vaccine. What's the development timeline from today until approval? I'm just curious, what data do you need to see in order to decide to make a phase III investment?
Yeah. As I said, phase II starts in a few weeks. Initial data readout in August. Again, if we just ignore the whole funding piece we've been talking about, we would be in a position to start phase III towards the end of this year. Again, if the regulators are still supporting accelerated reviews, we could see an approval mid of next year.
Got you. Maybe my second question is on the RSV. I'm just curious if we could set expectations for the human challenge study, specifically in terms of data that you need to see in order to move forward. Also, you outlined a timeline starting an RSV study in 2022. I'm just curious, with probably a lot of people still working from home and wearing masks, what do you need to see socially from social interaction to decide that 2022 is a good year to do an RSV study?
Yeah. First of all, the challenge component. In the challenge study, we're obviously treating or vaccinating subjects either with our vaccine or with placebo, and then they will be challenged with RSV. They'll be tracked for a period post-challenge. We're really looking for a significant reduction in the viral load in the blood.
As you know, these are healthy individuals, and even in the placebo group, they will eventually clear the RSV. You're really looking for a delta or a difference between the vaccinated arm and the placebo arm. We haven't publicly said what the threshold is that we're looking for, but I have publicly said before, if we don't see an effect, then obviously the program is not going to move forward. In terms of the trigger to start a phase III, it's a very good question.
We are tracking the incident rates of RSV, and they remain extremely low. I don't know whether you saw, GSK has announced they're initiating a phase III, and they updated their protocol from 18,000 subjects, I think it was, to 25,000 subjects just last week. My speculation on that is probably that's due to the low rates of RSV.
I think our decision not to move ahead this year has been endorsed as being far too risky, but we are monitoring it. It's a bit like the exactly same situation last year. We were monitoring it, and at some point, we had to make a decision, are we going or are we not going? We certainly need to see the rates of RSV raised to more normal levels that we saw before the pandemic.
Got you. Okay. Thanks for taking my question.
Sir, your next question comes from the line of Peter Welford from Jefferies. Please go ahead. Your line is open.
Hi. Thanks for taking the questions. I've got a few. Just sticking on COVID-19. I'm curious there, when you say for the phase II study that you're planning, that the roughly, I think part of them are seronegative and part of them are seropositive. Are the seronegative subjects who have had a vaccine or an infection and test negative at a certain time post that event and therefore, due to an underlying condition, I guess, or due to time, or are they actually patients who have not yet been infected or not yet been vaccinated?
Also, if you could just outline what the endpoint is, please, for the phase II study that you're looking at. Just with regards to Japanese encephalitis and cholera. Appreciate you've yet to transfer them into it, but I wonder if you could give us some idea of what you think the German market opportunity is currently for those, please, from Valneva. Then finally, just on J&J. Just curious there if you can give us any updates at all on the status of any of the J&J collaboration vaccines, whether or not there's any news we can expect on those or any other progress you can report. Thank you.
Thanks, Peter. On the COVID phase II, the seronegative arm currently is planned to be truly seronegative, so previously not vaccinated or infected. That's the group we're going for. On the seropositive arm, so these are people who have proven vaccination and the fact that they actually have antibodies. Clearly, timing is important here. I kind of get the question, that's why we're starting in a few weeks, and we'll be conducting that study in both the Netherlands and Germany, and we believe it is doable to identify those subjects.
Sorry, just to be clear, presumably you will test some of these patients for antibodies at the start, because obviously there is some potentially are asymptomatic, and I guess I am just thinking it is going to be increasingly difficult to necessarily know as well who has had a prior infection.
They will be screened and tested, yes. I guess it's only those people who have had a non-symptomatic infection that wouldn't know that they've been infected. There are quite actually a few of those. Yes, they will be screened, and they need to be negative serologically for SARS-CoV-2. Okay.
Great. The endpoint?
Oh, yes. Sorry. Obviously safety is an important endpoint always. The other endpoint is really looking for a significant increase in the neutralizing antibody titers.
That's great. Thanks. Yeah, Japanese encephalitis, cholera, and J&J, please.
I'll take J&J first. On J&J, unfortunately, the other collaborative programs that we have, they have been impacted by COVID. The trials are either put on hold or have been delayed in their initiation simply because it's just too difficult to recruit right now. On the other programs, we're not expecting any news flow in the near term.
On the two other products, Japanese encephalitis and the cholera product, I think we haven't guided any specific things relating to our expectations for these products. I think what we can say is that we are taking over these products in our markets from first of January 2022, and obviously, I think they are to a large extent travelers' vaccines, so that means they are negatively impacted as we speak here.
Hopefully, you can say we can put COVID-19 behind us and the market is back from next year when we actually take over the marketing and distribution responsibility in Germany for these products. As we get closer to that, I think we will come back and make sure that you're better equipped for the forecast expectations on these products as well.
Thanks, is it reasonable to assume, presumably, should we think of these products in HEPLISAV-B as largely being a way to cover the cost of your sales force rather than perhaps look at them as being a profit generator, so to speak, if that makes sense?
I think definitely. I think with adding these three products now to our existing infrastructure, we're really leveraging the investment we have done there. It's not something that will turn our P&L upside down. Clearly not, it is going to help us to cover that cost, and it will also make positive contributions to our bottom line for these products. I think it's a good way of leveraging, you can say, some untapped synergies that we are sitting on with a full commercial infrastructure and only two products in the bag so far in Germany.
That's great. Thank you.
Once again, if you would like to ask questions, just press star one. We've got another question comes from the line of Jesper Ilsøe from Carnegie. Please go ahead, your line is open.
Thank you so much. A question on the COVID-19 vaccine development as well. You have phase I/II and phase II data coming up. Besides safety data, what will you look at when you see? Can you hear me?
Yeah, we can hear you.
Okay, there was some disturbances on the line. What will you look at in the phase I/II data as you read across into your own phase II data? Also considering that you would do a phase II with a higher dose versus the phase I/II and the limitation you see in that phase I/II study. How certain is it that your vaccine can be a one-shot, also considering the much better neutralizing antibody titers pre-clinically with two shots versus one shot?
Tied to that, what is the most important factor in the data sets when thinking about phase III funding discussions and possibilities, i.e., what are these, say, organizations, governments we are looking at to make your vaccine stand out? Perhaps you can also touch upon the data you saw from Medicago and GSK as a read across into your own vaccine, and how you see the VLP-based competition in COVID-19. Thank you.
Yeah. Let me see if I remember all those questions, there was a few there. The ongoing phase I/II study is important because our collaborators are really looking at a range of doses starting low, which is the data I've indicated that we have now. They're also looking at adjuvanted and non-adjuvanted. Based on the preclinical data, it really looked as if we didn't need an adjuvant. That's kind of the assumption that we have made already, to go into phase II.
The encouraging thing is that already with the low-dose data that we have now seen, the two things that we're looking for is safety. Are there any signals that would be of a concern? So far, albeit with a low number of subjects, it looks very promising from a tolerability point of view. The other thing we really wanted to confirm was, do we need an adjuvant or not? AdaptVac in most of the data that they've generated preclinically have always used an adjuvant. We had little data to support our assumption that we didn't need it.
The initial data that we've seen has clearly shown that the adjuvant isn't really adding anything in terms of the immunogenicity of our ABNCoV2. Actually, as I sit here now, I think I already have the data I need to proceed into phase II, which is exactly what we're going to do. As I said, what we're looking for in phase II is a confirmation in the large number of subjects of safety. We also wanna make sure, to your point, that the single-shot booster in people previously vaccinated is sufficient to generate this strong, broad immune response.
We are encouraged by the preclinical data where the second shot really makes a big difference in animals that are already primed. We believe that in people previously vaccinated, primed either with the adenoviral platform or the RNA platform or any other platform, that we will be able to boost those responses very strong with this candidate, because it is clearly highly immunogenic and really generating strong immune responses. I'm just trying to remember some of your other questions.
The Medicago data. Yep. Obviously, always encouraged to see positive data coming out. It's a VLP technology, but interestingly, it is adjuvanted. The data that they're seeing requires an adjuvant. Again, I think what that points to me at least, is that the platform we have, yes, it's a VLP, but it's a superior VLP in my view, because we have a much denser expression or array of the RBD on the VLP, and we don't need an adjuvant.
As I've said, that's confirmed now in the phase I, but also in preclinical. Not having adjuvant will reduce the COGS, reduce the reactogenicity that you'll see when you get vaccinated and make our platform extremely competitive. Again, it's really encouraging to see that a VLP platform is generating very positive data.
Perfect. Thank you so much. Perhaps you can also touch upon what the most important factors are when taking discussions with, say, CEPI and the like, when they see your data. What's the most important factors there to make your vaccine stand out versus the competition?
Yeah. On that, CEPI specifically has got a number of applications out there. One is specifically on new candidate vaccines generating a broader protection. As I said, I keep saying it, I think we have the best preclinical data that anyone has. No one has shown the same neutralizing titers, particularly against the South African variant, as ourselves. That is putting us in a pretty strong position. The other application that CEPI is looking at is really for new candidate vaccines that can address the developing world.
Again, I think there with the ease of production, we feel confident that we can even address that, maybe through partnerships with others, but we can address that as well. I think when it comes to government or governments, it's really about hedging their bets. The EU's done a big deal, obviously, on the RNA vaccines. There's a lot of people raising concerns that maybe, are we putting all our eggs into one basket? As I said, there is now increasing data coming through where there is quite some alarming adverse reactions, systemic adverse reactions on repeated vaccinations.
It is also known with the RNA platform that you're really not getting the same sort of strong protection or immunity, I should say, against the different variants. I think we're well-positioned in our discussions that on the data that we have, and it's growing day by day, that we have a rather unique candidate that is addressing a lot of the concerns that exists right now, both from funding agencies like CEPI, but also governments around the world.
Thank you. Thank you so much, Paul.
Once again, if you would like to ask questions, just press star one. Sir, no more question at this moment. Please continue.
Okay. Thank you. Thank you everyone for attending the call and for your questions. Have a great day, and we'll catch up next time.