Good day, and thank you for standing by. Welcome to the Bavarian Nordic first quarterly report, Q1, for the three-month period ending 31st of March 2022. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during this session, you will need to press star one on your telephone. Please be advised that today's conference is being recorded, Monday, the 9th of May 2022. 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 Sørensen . Please go ahead.
Yeah. Good afternoon. Thank you, operator, and welcome to this Q1 presentation of Bavarian Nordic's first quarter results. As usual, I am here together with the A team, President and CEO, Paul Chaplin, and Executive Vice President, CFO, Henrik Juul. Before we start our presentation, just want briefly to walk through this 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 materially from the results discussed. Forward-looking statements include statements regarding our short-term objectives, opportunities, financial expectations for the full year and cash position as of year-end, as well as statements concerning plans, objectives, goals, future events, performance, and 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 would hand the presentation over to you, Paul.
Thanks, Rolf, and welcome everyone to the Q1 update. If you turn to slide three, I just wanna walk through a little bit of background on Bavarian Nordic. In the last two years, Bavarian Nordic has truly transformed into a commercial company. Of course, the journey continues as we have a big ambition to become one of the largest pure-play vaccine companies by 2025. Up till now, we have four commercial products, and to sell and distribute, we've built up an excellent commercial infrastructure, both in the U.S. and in Europe, and that allows us to drive strong growth, and have a strong financial position. You'll see that we've recorded at the end of Q1, a cash position of DKK 2.9 billion.
We're in a very strong financial position to continue the transformation and move towards our vision to become this largest pure-play vaccine company. Obviously, what we've achieved to date has built the foundation where we can add new products. We obviously also this year will be selling and distributing three additional products for other companies in certain territories. We wanna continue to add to our commercial portfolio through our internal growth. This year, in 2022, is a year of investment as we are investing in the future growth in two in-house programs, one for RSV and one for COVID-19, both of which will or have enter phase three during 2022. We will be completing the investment in our manufacturing here in Denmark, which will allow us eventually to bring our two new products for rabies and TBE in-house.
We will be finalizing the tech transfer of our freeze-dried JYNNEOS to our new state-of-the-art facility this year. This will allow us to unlock the current option with the U.S. government for almost $300 million, which will be revenue recognizing in the years ahead in 2023, 2024, and 2025. It's truly a year of investment. It's one that's been planned, and it's one, obviously, with the successful completion of RSV and COVID-19, will allow us to fulfill our vision to become the largest pure-play vaccine company by 2025. If you go to the next slide, just some of the key highlights from an extraordinarily strong quarter in terms of our pipeline progression.
On RSV, we saw a breakthrough designation from the FDA, which means after review of our data to date, the FDA has concluded that this program is likely to meet a high unmet medical need in terms of preventing RSV infection in the elderly. It'll also allow us to have expedited review and allow us to further accelerate the regulatory process for this program. Later in the quarter, we secured a license agreement with Nuance Pharma, who will distribute and sell our RSV vaccine in China and selected Asian markets. This is part of our partnering strategy to ensure that we can sell and distribute this product when we launch.
Then in April, we initiated the phase three trial as planned, which will enroll 20,000 subjects this year and will read out in the first half or mid of next year in 2023. Our ABNCoV2, our COVID-19 vaccine candidate, has also seen a lot of activity in this quarter. We've reported additional phase two data, which I'll come to later in the slides, and we are on course to start our phase three program. However, as I'll come to in later slides, the regulatory environment is changing, which may change some of the timelines in terms of initiation, but we're still confident that we'll be able to report the data and continue the filing process later this year.
In terms of the sales of our commercial products, I know Henrik will be coming back to that, but we've seen some positive growth of our rabies business, albeit coming from a low point in Q1, and our TBE franchise is a sluggish start with a decline in the market. The main quarter for TBE is Q2, so we're hopeful to see some sort of a rebound later this year. We've added to the executive management with the arrival of Russell Thirsk, who is a highly experienced individual coming out of GSK, and I'm sure he will be a strong contributor to the team moving forward. If we go to the next slide 5, let's talk a little bit about ABNCoV2. I'm frequently asked, why are you continuing to develop a vaccine? Aren't you too late?
We already have vaccines on the market. My answer to that is, yes, it's true, we have vaccines on the market that has allowed us to come out of lockdown. However, the data from those vaccines is clearly showing that the level or the durability of protection is quite short and wanes even within six months. It's really not even providing protection for a full flu-like season, and therefore, there is an unmet medical need for better vaccines giving you longer-lasting protection. We believe with ABNCoV2, which is based on a virus-like particle technology that is designed specifically to stimulate strong B-cell responses, that we will address the durability issue and have an improved vaccine.
To date, we've reported phase two data that shows exactly that this vaccine, which is designed specifically to stimulate B-cells, is generating very strong antibody responses to all the variants of concern, including Omicron, to levels that have been reported to be associated with high levels of efficacy greater than 90%. We're really now geared up to start the phase three and really evaluate this vaccine in a head-to-head comparison with an RNA-based COVID-19. Up until a few weeks ago, we were about to start a study which we've reported before, which was utilizing national booster programs where we would get access to the comparative vaccine in these national programs, because we had previously been told that member states in the EU and in the U.S. could not provide the vaccine directly to companies.
That situation has now changed, or I should say is changing in the EU, at least, and that we've had indications that member states in the EU have the potential to provide vaccines to companies. Under that development, we really have to change the trial design and truly do a randomized head-to-head comparison with the RNA-based vaccine. This, however, is seen by us as a very positive development. A randomized controlled study is a lot easier to conduct than trying to enroll subjects in a national booster program. Many of the national booster programs are coming to a halt in Europe, and it was challenging to find sites that we could enroll. We see this as a positive development. However, in this, you know, just as we were about to start the other study, this development comes, so it will have an impact.
We're hopeful that that impact will not be that great, and we're still very, very confident that we'll be able to read out the results later this year, and if allowed by the regulators, continue to file the rolling BLA by the end of the year. Let's move to the next slide, and let's talk about some of the latest data. Just to try and explain this data, as you know, in the phase two study, we evaluated two doses, 50 micrograms and 100 micrograms, and we've previously concluded that both doses gave very highly comparable results. What we're showing you here is both groups combined and the neutralizing antibodies that were generated two weeks post-booster against the various variants of concern.
The last cluster is the Wuhan strain, which obviously is the original strain, and then the various different variants of concern, both the fold increase and the GMT. You can see that, similar to other vaccine candidates that have reported, neutralizing titers against different variants of concern, it goes that Wuhan and Alpha are very, very similar. Then you get Delta, Beta, and the lowest response is always against Omicron, and that is true with our data set. However, it should be noted that while Omicron is generating or we're generating the weakest antibodies against Omicron, it's still at levels that have been associated with efficacy above 90%. We're very, very happy with this data set.
It is showing the concept that we're developing the vaccine for as a universal booster, and we will be entering phase three very shortly. The comparator will be against an RNA vaccine against the Wuhan variant, as we've agreed with the regulators. Let's turn to the next slide seven. A little bit about RSV. RSV is often a disease that goes unmissed or unrecognized by many investors and the community. However, RSV causes as many deaths in the elderly annually as influenza. However, what many people also don't realize is that the burden of disease is much higher for RSV than flu.
What I mean by that is the stay in hospital, if you are hospitalized, is longer, and the mortality post being hospitalized is higher if you've been hospitalized with a severe RSV infection than if you've been hospitalized with flu. There's a huge unmet medical need for a prophylactic vaccine that will prevent infection in the elderly and in risk adults. We have a completely differentiated approach in our vaccine candidate that has shown some excellent immune responses in phase two. Last year, we reported on some exceptional efficacy in a human challenge study of almost 80%. An exciting candidate, one that clearly meets the criteria to be evaluated further in phase three.
In April, we began enrolling in the phase three study, which will enroll 20,000 subjects both in Germany and in the U.S., and will read out in the first half of next year. As I said, it also has a breakthrough designation from the FDA, which again is confirming the excellent data set that we have, and we've already begun to think about launch with a partnership with Nuance Pharma for China and selected Asian countries. With that, I'll pass over to Arne. One more slide. Slide eight. Just one last word. We are investing a lot in 2022, and part of that is also completing the investment in our manufacturing facility in Denmark, which is going on track, on budget. Excuse me.
When this is completed, later this year, it will allow us to truly start the physical tech transfer of our rabies and TBE vaccine, which we'll be able to manufacture at this site by 2024. It will also allow us in parallel to manufacture other MVA-based products, such as JYNNEOS or our Ebola vaccine or our RSV vaccine for launch. So as I said, it's a great investment that's going according to schedule, and it's really building up a center of excellence in terms of manufacturing of viral-based vaccines. With that, I will now hand over the presentation to Henrik.
Thank you, Paul, and good afternoon, good morning to all the listeners. Let's turn to slide number ten. I will start with a quick overview of the revenue generated during the first quarter of 2022. In total, we delivered revenue of 320 million DKK, which was 40% lower than prior year, which included a significant revenue related to our BARDA business, and which, you know, most of you is quite sort of chunky business, that happens in some quarters and not all quarters. Let's have a quick look at the individual lines here.
Our Rabies business with Rabipur/RabAvert and RabAvert delivered total revenue of DKK 117 million, up 45% compared to prior year, and driven by extremely strong market performance both in the US and in Germany, which I'll come back to on one of the next slides. In contrast to this, Encepur delivered DKK 69 million, so 30% down compared to prior year, due to a still unfortunately depressed TBE market in Germany. Here, we should also remember that we are comparing against a strong first quarter of last year, where we saw an 8% positive growth, which gave us optimism for the TBE market coming back. During the first quarter, we also delivered DKK 30 million revenue in our IMVAMUNE, our Ebola vaccine to Janssen.
This was finalization of the order that we executed upon last year, so no more revenue is expected on Ebola for this year. We delivered the first revenue on the two products that we have an agreement with Valneva on, so that's the IXIARO and Dukoral products that delivered a total revenue for the first quarter of DKK 40 million. Then we also saw a nice milestone revenue being recognized from the agreement we signed with Nuance Pharma for China and selected markets on RSV. $12.5 million translated into DKK 83 million. Finally, we have a little contract work mainly related to the qualification of the fill and finish facility and the BARDA contract.
In total, DKK 300 million for the first quarter. If we turn to the next page, let's spend a little time. This is a build. I will just show all the builds here. Talking a little about our Rapis business, and if we first start looking at the markets, the US market showed strong growth, 22% compared to the same quarter of last year, and getting to a level close to the pre-COVID-19 levels. Continued strong growth in the US market, and we are nearly looking at a market that is back to pre-COVID levels. If we look at the German market, that was really a market that was severely hit by COVID-19 as people were not traveling to exotic destinations.
However, we have during the last three quarters seen strong growth from a low level though. I think here in the first quarter, it's actually a 257% growth. Despite that it comes from a low level, the growth is material enough to have an impact on our total numbers. Therefore, you also see strong Nordic revenue on the Rapis business, 117 million DKK, so up 45% and really driven by both the U.S. and the German markets. We have on the market share basis that the U.S. market share ended at approximately 64% after the first quarter, which is in line with the level we saw prior to our competitor facing a stock out situation in the autumn of 2020. Really strong performance in the Rapis markets and by our team.
Next slide. Again, this is a build slide. This slide talks about the TBE market, where Europe is representing most of our business, or sorry, Germany is representing most of our business here. Unfortunately, what we saw here in the first quarter is that the sort of the depressed situation we have seen the last quarters in the German market for TBE continued, and we basically saw a market being down by 23%, compared to the same quarter last year. Based on our intelligence in the market, I think what we are seeing right now is that there is, again, access to physicians is there. We suffered from that in the past as physicians were occupied with the COVID-19 vaccinations. That is not so much the problem any longer.
Now it's mainly coming from a weak demand from patients. There's some indications of some temporary vaccination fatigue among people who have been vaccinated one, two, three or even four times with the COVID. There is at the moment relatively poor public press coverage of TBE. I think this is unfortunately a trend that cuts across many vaccines in the space. It's not only TBE. I think if you look into some of the big vaccine companies like GSK and Pfizer, and you look into the performance of their vaccines in Europe, you will see the same tendency that the vaccine market is unfortunately still depressed in Germany. We are, however, still optimistic that this market will come back relatively soon. We have, as Paul alluded to, expectations to the second quarter.
Second and third quarter are the most important quarters for us in the TBE business. Hopefully we will see some signs of the markets coming back here in the second quarter already. Our performance in Germany on Rabipur shows that there is pockets within the vaccine space with good growth already. We remain optimistic that also for the TBE market, we are going to see growth soon. On the next slide, that is just to remind you about the marketing and distribution partnerships that we have concluded. The two bottom ones, IXIARO and DUKORAL, we made the partnership with Valneva, and we have already launched these two products in Germany and in Switzerland and delivered the first DKK 40 million in revenue during the first quarter.
We have the third one, HEPLISAV-B, which we have in license from Dynavax, and which we are planning to launch here in the second quarter in May this month, actually, to be more precise. This is going to be a launch in Germany only. It is a quite exciting launch as this is a real first time launch of this product in the market. On slide fourteen, quick overview of the total profit and loss. As already presented, revenue of DKK 320 million.
We had total production cost of DKK 292 million, leading to a gross profit of DKK 28 million, a relatively low gross margin, partly due to the plant shutdown of the bulk facility, which means we have less production costs being absorbed by the manufacturing of revenue generating products. Research and development costs ended at DKK 105 million, somewhat lower than the same period of last year, and primarily explained by the fact that we manufactured all the RSV phase 3 material in the first quarter of last year. SG&A costs came in at DKK 115 million, below last year's level and primarily due to lower distribution costs and commercial costs.
Adding net financial items and tax, et cetera, it takes us to a net profit for the period of DKK -272 million or an EBITDA of a loss of DKK 94 million. Remember, EBITDA is the level that we guide on. These two or this slide here includes two of the parameters that we guide on revenue and EBITDA. Based on these results, which are overall in line with our own expectations, we are confirming our guidance for the full year on these two parameters. Next slide, quick overview of the cash flow and our balance sheet. Net cash flow for the period was a negative of DKK 192 million. We saw positive contribution from operating activities of 24, driven by improved working capital, primarily with lower receivables during the quarter.
We saw a negative contribution from investment activities of close to DKK 300 million, where that more or less equally split between investments in plants, the expansion of our bulk facility, and the other part going into investments in intangible assets, which includes our tech transfer process of Rabipur, RabAvert, and Ensifur, and our development of the COVID-19 vaccine that we are capitalizing. Finally, we had a positive contribution from financing activities of a net of DKK 75 million, and it's primarily explained by another DKK 80 million we got from the Danish Minister of Health as part of the agreement we signed last year.
To the right, we see some selected balance sheet figures, and I will only for now focus on our net cash position, so that is the DKK 2,594 million when we have excluded all debt. If we add back the current engagement with the European Investment Bank, that takes us to a current cash and cash equivalent position of DKK 2,947 million, which brings us in a very strong position to continue pursuing our strategy and all our plans, including the phase three trials that we either have or will initiate very soon. If you go to the next slide. I already mentioned that we have confirmed or maintained our guidance for the 2022 revenue and EBITDA, and I can say the same on the cash position based on the previous slide.
That is, we still have a guidance in terms of revenue of between DKK 1.1 billion and DKK 1.4 billion. We are guiding earnings before interest, tax, depreciation, amortization. Guiding here a loss between 1 billion and 1.3 billion Danish kroner. We are guiding a cash position by the end of year of between DKK 1 billion and DKK 1.2 billion. To the right on this slide, you see our usual overview of key activities and key milestones for the remainder of the year. I will just highlight a few of the most important ones. Obviously, if you look on RSV, we already initiated the phase 3 enrollment. The next important milestone is, of course, to complete enrollment, which we are planning to do, by the end of 2022.
COVID-19 next, major important milestone will of course be the initiation of the phase three trial. As Paul alluded to, we are still targeting to complete or have the first data readout from this COVID-19 trial, and if the regulatory bodies allows it, start rolling submissions already this year. If you look further down, I already mentioned it at key important commercial milestone will be to have a successful launch of HEPLISAV-B in Germany, which will be initiated here during the months of May. Just final remarks. Overall, we are happy with the financial results we have seen, and therefore we are in a position where we can maintain our guidance for the full year despite all the uncertainties in the world at the moment.
With that, I will ask the operator to open up for questions.
Thank you. As a reminder, to ask a question, you will need to press star one on your telephone. To withdraw your question, please press the hash key. Please stand by while we compile the Q&A roster. Your first question comes from the line of Gil Blum from Needham & Company. Please ask your question.
Morning, good afternoon, everyone. Thanks for taking our question. Maybe a broader one, considering trends that we've seen both in Reuters and TD. What do you think are the attitudes of the average European towards COVID right now? I would say that in the US there's a bit of a reading through COVID, but I would appreciate your commentary around this. Thank you.
Yeah. I can take that. Well, I can speculate if you want. I think, you know, as Henrik alluded to, there seems to be a little bit of fatigue, vaccine fatigue. I don't know whether there's a better word for it, in Germany at least.
where we're seeing a slower than normal uptake, not only of our vaccines, but others are reporting the same thing. I think there is some fatigue out there. I think, you know, in Europe at least, you know, all the lockdowns have essentially come to an end and we're all back moving around, and people tend to forget about COVID when the sun is shining and things are getting back to normal. I do believe, however, you know, it was the same last year, this time last year. Then of course, Omicron emerged, and there was obviously a need for everyone to get a third booster. I feel the sentiment will be very similar as last year. We're all happy and we've forgotten about COVID.
As we get near the autumn, I would imagine the number of cases will increase, particularly as the data is showing that the third booster really wears off before six months. I would imagine that, whether there's fatigue or not, we're gonna need to get revaccinated in the autumn.
Thank you, Paul. That, that's very helpful. Maybe a follow-up question just to remind me of what do we think the primary endpoint is gonna be for the pivotal study of your COVID vaccine? Thank you.
Yeah. It's to demonstrate non-inferiority of the peak neutralizing titers against Wuhan between AD and COP2 and an RNA comparator.
It's not, and will include like secondary endpoints such as, you know, rate of hospitalization and things like that.
Well, it's a smaller study. While obviously we'll be looking at hospitalization and real cases of COVID, it's not powered for that. It's purely an immunogenicity endpoint. Obviously, there are secondary endpoints. Safety, of course, is a key one, but also looking at the immune responses to other variants of concern. The primary endpoint, which will allow for registration, is a non-inferiority immune endpoint to a comparator RNA.
Okay. Gotcha. Thank you very much for taking our questions and, congrats on the progress.
Thank you.
Thank you. Your next question comes from the line of Peter Verdult from Citi. Please ask your question.
Thank you, Peter from Citi. Just one for Paul, really, on the timelines, phase three timelines. For COVID, are the timelines to still be in a position to file this year? Is that a sensible base case, or would you concede that it's optimistic and that the risks on the timelines are slipping is quite high? Just wanted to get a sense with the changes that you're having to deal with in the trial design, where the risks are. Similarly, as you get ready with the RSV program, prevalence rates we're seeing, enrollment rates, does that still give you confidence that you'll be having that data mid-year? How much confidence do you have that you'll be having that data mid-year? I think one of your competitors, the timeline slipped somewhat for their phase three re-readout.
It's just the confidence around the timelines on the pivotal phase three programs. Thank you.
Yeah, thanks, Peter. So on COVID, as I said, this latest regulatory development is relatively new, unfortunately. So that's the unfortunate side of it. You know, we were literally about to start the previous study. I call it previous because we have to adapt. The reason we definitely have to adapt is that the approval that we had with the regulators was that they were happy for us to conduct to enroll in a national booster program only if we could not get access to a comparator. So as soon as the door opened that it looks like we can now get access to a comparator, you know, the regulators have clearly stated, then you have to do a fully randomized study to the comparator.
The good news, as I said in the presentation, that is a simpler study to conduct, potentially even faster, and that's why I'm saying that any slight delay we have in the start, I think will lead to a faster study. The other thing, just to raise your own confidence that we are confident, is that I've said several times we were working in parallel on both approaches, both a randomized study design, but also, going in with the national booster program. Obviously, for many months now, we've thought the national booster program was the approach, but we actually have draft protocols and things that we've already discussed with the regulators for the randomized approach.
I think we can catch up relatively quickly, but as I said, it is a relatively recent development, so I can't be very firm on exactly when we'll start that study as we're still in dialogue with a number of member states to actually get access to the vaccine. We are confident that we should foresee data readout later this year. As I said, if the regulators allow it, we'll start the rolling submission. In terms of RSV, obviously we've only just started enrollment, which is the critical phase.
Enrollment is going okay, and the site opening is going okay. We're on track as we stand. As I said, we're only one month in. There is competition, as you know. There are a number of competitors also conducting RSV studies, and even those, some of those that started last year have expanded their study and are also enrolling. We've taken that into consideration in the site selection. Yes, we remain confident that we will enroll 20,000 this year, and that we hopefully, you know, the data readout next year is dependent that we see the total number of events that we need to read out. If that's the case, I do believe we'll have data next year.
Thank you.
Thank you. Once again, if you wish to ask a question, please press star one on your telephone. Your next question comes from the line of Peter Welford from Jefferies. Please ask your question.
Hi. Thanks. Yeah. Four questions. Hi. Sorry. That should be better now. I've got four questions for Kammy, please. Firstly, just on the timing of the booking of revenues under the for the JYNNEOS for the U.S. government and Canada. Should we assume that the bulk of these happened at the very end of the year, given the manufacturing and what's going on, or is this unrelated to what's going on there? And it could be, it could happen, you know, during the earlier quarters of this year. Secondly on Encepur in Germany, you mentioned vaccine fatigue and then a sort of unwillingness. Is this something you're considering actively addressing?
I guess I'm thinking with regards to marketing, perhaps some campaigns to get out there, to address, you know, the potential lack of willingness by people apparently to go forward to it, or is this something that a more general aspect that you're basically gonna wait for the next season at this point in time? Thirdly, just on the outlook, obviously you've had the milestone from RSV, from Nuance Pharma, and also FX obviously is moving much more in your favor, by 10% or so on the dollar, versus the original guide. Are we therefore in a situation where we should be thinking about, you know, some of the weaknesses and things like Encepur, et cetera, you know, give you the confidence that actually there's a sort of offset here?
Should we be thinking more that given the milestone and given FX, that realistically, you know, the upper end of your guidance is more sensible at this point now? Just finally on COVID, coming back to the primary endpoint, I understand obviously the choice of primary endpoint as standard, but is it potentially under consideration to perhaps do a slightly larger study and also look at some of the other strains as secondary endpoints? I'm thinking particularly Omicron. Would it be viable to consider trying to show superiority, given obviously we know that the existing mRNA vaccines don't necessarily induce strong immunity against some of the new strains? Is it possible to try and tease out some sort of benefit?
I guess I'm just thinking from your perspective, coming late to the market, this seems potentially like an opportunity where you could actually use this study to your advantage at this point, or is it just realistically too costly and too big to be able to achieve those sorts of measurements? Thank you.
Yeah. Thanks, Peter. Let me take the first couple of questions here. First of all, timing of the revenue from JYNNEOS. We have in our guidance included the Canada order, approximately DKK 200 million, and then we have DKK 100 million left over from the orders from last year. That's DKK 300 million in total. The BARDA order, the DKK 100 million, cannot be executed until we have opened the bulk facility again. That will be in the fourth quarter. The Canada order, I think we are expecting most of that to happen in the second half of the year. Most part of our smallpox revenue, the DKK 300 million, will take place in the second half of this year.
In terms of Encepur Germany, what can we do to help the market turn around, and is this something we can address last in terms of marketing, et cetera? I think we are basically doing everything we can here. I think we should also remember that we have approximately 30% of the German market. Pfizer, a strong market share, sits on 70% of the market. They should really be turning this market around, and they will be gaining most from it. According to our own intelligence, they are doing what they're supposed to do.
What we are lacking right now is there's not much communication from national authorities in the market, which there usually is, where people in sort of national campaigns are reminding people about the tick season kicking in and the risks of not being vaccinated, et cetera. That's probably where more can happen. We of course doing our best to push for this to happen again. I think the good thing is that we are seeing, as we said, pockets of vaccine markets developing well. We saw our Encepur market in Germany showing fantastic growth. We do see this as a temporary phenomena and are optimistic that the TBE market will also return in the near future.
In terms of our outlook, you're right, we haven't changed our outlook, despite we got the Nuance milestone payment, which was not in our original guidance. On the top line, we are helped by a stronger dollar, that's correct. We simply believe with the uncertainties that we are seeing in today's world, that it was just a tad too early to change anything in terms of our guidance. We are a little uncertain about, of course, how Imsevikuu will develop, despite we are optimistic. I will assume that we will have a close look at this again in connection with our second quarter report. For now, I think we have concluded that it's a little too early with all the uncertainties we are seeing in the world at the moment to change the guidance.
On the forex, remember also that the currency might help us on the top line. Unfortunately, not so much on the bottom line as a lot of the clinical trials that we're investing in are in U.S. dollar-denominated. Then I think there was a question.
Yeah.
To you, Paul, on the primary endpoint on COVID.
Yeah. Thanks, Peter. The primary endpoint really is locked in that the regulators, and when I say regulators, that's EMA and also the FDA, have been pretty insistent that the primary endpoint should be only against the Wuhan strain, which is the only strain any vaccine has shown efficacy against, or at least the RNA vaccines. To go to superiority claim there, we probably won't get away with that as an endpoint. Don't forget against Wuhan, we're looking at 95% efficacy. It's gonna be very difficult to trump that, to be honest. Having said all that, of course, the secondary endpoints, we will look at variants of concern.
While secondary endpoints may not be allowed in the so-called label claim, of course, if we can generate superior data, that may well be used by other bodies such as ACIP, who, you know, make the final recommendation in the U.S. anyway. We are trying to address some advantages that we may think we have over the RNA in terms of the overall trial design. As I said, the primary endpoint is really locked in.
Sorry, just follow up. I understand totally on the primary endpoint, I guess. My question was just on the last point there, which is given what you've seen with Omicron and the neutralizing antibody titers that you generated, it's when you think about the sizing of this study, are you thinking about potentially sizing appropriately to get as possible superiority the NAbs against Omicron? Because I would imagine, you know, the trial size to achieve that is probably not massively, but fairly significantly larger than the trial size required to just show non-inferiority against Wuhan on the primary endpoint immunogenicity.
I think you've answered the question for me. It's exactly that's the problem. This trial size would be significantly larger. It will take longer, and then you may still miss that endpoint. I think, you know, I think the risk, the expense and the timing risk is too great to go for such a trial design.
That's great. Thank you.
Thank you. Your next question comes from the line of Michael Novod from Nordea Equities. Please ask your question.
Yeah, thanks a lot. First a question on RSV. Maybe, Paul, you can explain a bit on sort of the importance of the T-cells, especially regarding hospitalization, which is the primary endpoint in phase three. Also with the data in mind on nirsevimab we saw earlier. Just to get a feeling on how you actually differentiate or how you believe you differentiate also versus other data readouts coming out rather soon, probably. Secondly, on the rabies business, can you explain the big jump? Did you get some contract wins in the U.S. during the quarter, during the end of last year to sort of explain the significant jump also in revenues compared to the market?
Then lastly, third-party revenues, you're starting to book more and more. Maybe Henrik could detail a bit on what sort of level we should expect, just for modeling purposes in 2022.
I'll take the first one. Thanks, Michael. Yeah, one of the big differentiating factors is indeed the T cells, as you mentioned. You know, when we were developing this RSV candidate vaccine, we only really saw full protection in animal models when we had all five antigens from RSV expressed in our NDA. What we see in preclinical studies is that T cells play a very major role in clearing the virus. That's also seen in the clinic, and there's a number of publications that point to that fact. When you look at some publications looking at the human challenge model, neutralizing antibodies in the blood do not correlate with protection in that model.
The two parameters that do correlate, however, is IgA from nasal swabs, which is a special type of antibody in the mucosa, and T-cell memory T-cells in the lung. Also, there's a publication looking at a group of elderly subjects and looking at factors which was correlated with the fact whether they got RSV in a normal season or they didn't. Here again, neutralizing antibodies in the blood did not correlate with being protected from RSV. What did correlate in protection was whether you had a strong T-cell response before the RSV season. Again, indicating that T-cells play an important role. You brought up the therapeutic antibody data recently that was published, I think it was in The Lancet.
That was a very interesting publication because that therapeutic antibody in children showed very high efficacy from mild RSV symptoms. When you looked at hospitalization rates for severe disease of RSV, there's absolutely no difference between placebo and the therapeutic antibody. What I conclude from that, and all the other bits of data I've just said, is that T-cells play a really important role. In the absence of T-cells, such as a therapeutic antibody, you don't prevent the hospitalization and the severe disease, you're only preventing mild disease. We're the only vaccine candidate that generates a very strong and broad T-cell response against multiple RSV antigens. Time will tell, but it is a differentiating factor, and there is a lot of data pointing that we have a very good vaccine design.
Yeah, okay. Thanks, Michael. Let me take the question on rabies first. I think, yeah, we showed extremely strong growth, 45% in total. It's actually not explained by any particular contracts or such in the U.S. It is really, I think, the abnormal growth is really explained by what we see in the German market. The German market grew by 257%, and it comes from a very low base. Here we should remember that we have more than 90% of that market in Germany. We are having a huge benefit of the market coming back. Actually, if you look at the total growth in absolute terms, in our rabies business, it's more or less equally divided between U.S. and Germany.
Of course, we did see a nice growth in the U.S., but it's actually from the 22% we saw in the U.S. and to the 45%, that is actually explained by the significant growth in Germany, given our strong market share there still. I'm afraid I missed your second question. You wanted some input on revenues to be able to model for 2022. Which product did you talk about?
No, it was more the third-party revenues that you're booking, so from partnering products. It was more to get a feeling of that, and you're also starting to book additional products for the rest of the year, just to get a feeling of where we are, sort of in terms of the share of revenue pool.
Yeah. We haven't guided anything there yet, and it's still relatively new business to us. I do not feel comfortable starting guiding on that, and particularly not on HEPLISAV-B, which is a totally new launch. It's quite an exciting launch, of course. Total market value, EUR 20-25 million for the German market. Where we hopefully come in with a strong product, it's so far the only two-dose only hepatitis B vaccine coming into the market. In terms of the other two products from Valneva, I can't really guide on that. It's a little too early, and it's also two products that have been heavily impacted by COVID-19.
We need to see perhaps if some of the positive trends we have seen on rabies business also will spill over to other travel vaccines. That's a little too early to say, unfortunately. I'm afraid I can't help you much more, as we have very few data points on these new products here.
Okay. Thanks a lot.
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