Valneva SE (VLA) Earnings Call Transcript

Okay. Thanks, everyone. I think we're going to get started. Hello, and thank you for joining us for Valneva's Investor Day. I'm Josh Drumm, Vice President of Investor Relations, and it's my pleasure to welcome you this morning, as well as those listening on the webcast. Today, you're going to hear from Valneva's management and senior leaders about the company's near and midterm value drivers, including its late-stage development pipeline, commercialized vaccines and select preclinical vaccine candidates. In a few moments, I'll introduce CEO, Thomas Lingelbach, to provide a brief overview of Valneva in our late-stage development pipeline. Thomas will then hand it over to Katrin Dubischar, Director of our chikungunya vaccine program to provide an overview of VLA1553, including recently reported data. Katrin will then welcome John Kanaras, General Manager of our U.S. Subsidiary to discuss the commercial outlook for our chikungunya vaccine candidate. This will be followed by a discussion from Thomas on Valneva and Pfizer's Phase III vaccine candidate for Lyme disease, VLA15 also including recently reported follow-up data from an ongoing Phase II study. Thomas will then introduce our preclinical pipeline and welcome Anders Lilja, Valneva's Director of Preclinical R&D to provide some additional detail on select preclinical programs. Our CFO, Peter Buhler, will then provide an overview of our commercialized vaccine products as well as a brief financial overview before opening the floor for the panel to take your questions. [Operator Instructions] Before we kick things off, I'd like to remind listeners quickly that during this presentation, we will be making forward-looking statements, which are subject to certain risks and uncertainties that could cause actual results to differ materially from those expressed or implied by these forward-looking statements. You can find additional information about these risks and uncertainties in our periodic filings with the Securities and Exchange Commission and with the French market authority, which are listed on our company website, www.valneva.com. Please note that today's presentation includes information provided as of today, December 6, 2022, and Valneva undertakes no obligation to revise or update forward-looking statements except as required by applicable law. With that, it's my pleasure to introduce Thomas to begin today's presentations.

Many thanks, Josh. Good day, everyone. Great pleasure to have you here, and those are also on the webcast. Yes, Valneva. As you know, Valneva is a fully integrated specialty vaccine company. We are focusing on the development, manufacturing and commercialization of prophylactic vaccines for infectious diseases in areas of high unmet medical needs. We take a highly specialized and targeted approach to the development of our vaccines. And what does it really mean? It means that we are technology agnostic. So which means we go by indication, we pick an indication where we believe that there is value in generating a vaccine preventable solution. And then we pick the best possible technology for it. We are not a technology company. We are a disease company that focuses really on where we can make a change to people's life. We have a very highly experienced team at Valneva. Some of my colleagues are with us here today. And we have shown something that not many biotech companies can say. We have brought products from the bench to global licensure. And of course, we have an infrastructure around our manufacturing operations, which especially in the world of biologics is key. And we decided a few years ago to build a strong position in travel vaccines. As such, we built our own commercial infrastructure. And I'm glad that we have the representative of our single largest commercial subsidiary today with us, John. In order to really best position our travelers vaccines in the market, and our ambition is to grow the travel franchise further. When you look at our value proposition today, there are basically 4 key pillars. You know that the company has been going through quite, I would say, a momentous period over the past 18 months going into COVID, out of COVID and respective development activities. But we have kind of reshaped our strategy towards continuing with our advanced clinical development programs and clearly focus here on CHIK launch globally and with Pfizer to progress our Lyme program as quickly as we can. Then to rebuild the pipeline. We positioned quite a significant number of our R&D staff and allocated them to our COVID vaccine development activities, which resulted in a kind of a delay in bringing preclinical candidates into the clinic and towards the clinic. And we have, of course, now reactivated this engine and go full steam towards preparing the next clinical candidates. And we are also -- and this is part of our strategy, evaluating assets for potential in-licensing. I mentioned already our commercial products. We're going to hear more about it. But it's very clear that we are focusing on maximizing the opportunity around travel -- around travel vaccination, which is an exciting feel in vaccines. And with regards to COVID, we are still sitting on a bunch of inventory doses, and we are trying to deploy this inventory into international markets. Of course, having gone out of COVID meant also for the company to resize its operations. And we are in the middle of this process right now as we speak and expect the saving of approximately $12 million on an annualized basis. Looking at the pipeline, you will hear about our chikungunya program, our Lyme disease vaccine program, we used to work on C. diff. We were one of the companies that brought C. diff program to end of Phase II. We shafted at that point in time, and we are now looking for potential partners following, I would say, some bivalent results that others kind of presented around C. diff. We are in the process of evaluating our Zika vaccine candidate for reactivation in the clinical development, which is, again, a very important point, given that Zika got now on the blueprint by WHO, there is a clear demand for Zika vaccine. And we follow 100% the WHO target product profile having used an inactivated whole virus based approach for our Zika vaccine. Then we will talk more about the commercial products. You will hear that from Peter later, and we will then wrap up also with an outlook around what's next, including our COVID activities. With this introduction, I would like to hand over to Katrin.

Good morning. So good morning. It's a pleasure to be here today and talk about our chikungunya vaccine candidate. And I want to start off with talking a little bit about the disease itself. So chikungunya isn't a very well-known disease, but it's actually a major public health concern. The disease is often described as associated with low mortality, but with very high morbidity. And this is owed due to the fact that, in contrast to some other arboviral diseases, chikungunya is very highly symptomatic. So up to 97% of people who get bitten by an infected mosquito will develop symptoms of chikungunya. Those symptoms are primarily high fever that has a very acute onset and pain -- joint pain. And the joint pain for chikungunya has been described to be really severe, very painful, so actually, the name of the disease comes from an African word for -- from a Kimakonde word for meaning to be contorted or to be bent up because of the painful experiences of those people that aren't able to stand up right anymore. Chikungunya doesn't only have an acute phase. It progresses to a chronic phase in around 43% of the individuals. And that chronic phase can last months to years and can also be associated with severe joint pain. So there is a high burden of disease owed both to the very high symptomatic acute phase and the chronic symptoms that can really be a debilitating disease. People are sometimes unable to work. And so there is a high economic burden also associated with the disease. Outbreaks of chikungunya have been described on many continents, including in the Americas. And there is a potential for outbreaks to also happen in Southern Europe or in Southern United States where the [indiscernible] mosquitoes that can transmit the chikungunya virus are residing. And that has already happened. For example, we've seen chikungunya outbreaks in Italy. These outbreaks in the regions that I just described can take place if and in fact, the traveler returns and is still in the viremic phase of the disease. Therefore, they can spark a local transmission if they return home and are bitten by a mosquito, which will then be able to pass the infection on. At present, there is no symptomatic -- there's only symptomatic treatment against chikungunya, no targeted antivirals, and there is also no vaccine available to date. And with that, clear unmet medical need, we've set out to develop our chikungunya vaccine candidate. We're using a live-attenuated technology for our candidate targeting to induce a long-lasting immunity with a single dose. And as I'll speak more to later, we've completed our clinical program that will be supporting our BLA filing with the FDA. We've been able to achieve a number of important regulatory milestones over the last years, including the start of our BLA submission as the first chikungunya vaccine program globally, fast track and breakthrough designation, the prime designations. When we think about the target populations for our chikungunya vaccine candidate on the 1 hand, we're seeing the use of this in Western countries in travelers, in military to support true readiness and also for outbreak preparedness reasons. We also, of course, have a medical need in endemic regions. Many of those are in low middle income countries. And therefore, we've partnered with Instituto Butantan and CEPI. I'll briefly introduce the licensure pathway for chikungunya vaccines ought to the specific epidemology, which includes short-lived, very explosive but short-lived outbreaks, classical efficacy studies are not considered feasible for chikungunya vaccines. And therefore, regulators have agreed to license chikungunya vaccines based on serological end points. In the U.S., this pathway is referred to as the accelerated approval pathway. That's a brief overview of our clinical trial profile supporting our BLA submission. We've conducted a Phase I clinical study in 120 adults. We've tested 3 dose levels of our vaccine candidate and also included the revaccination in that study. In terms of results, we've seen that the vaccine was highly immunogenic with a single immunization. We haven't seen anamnestic response after the revaccination, confirming that this is truly a single-dose vaccine candidate. And we've seen a supportive safety profile with those data. And since we didn't need to confirm any further schedule optimization in a Phase II clinical study, we've been able to advance directly into Phase III trials. We've conducted a pivotal Phase III trial that was a placebo-controlled randomized controlled study, looking at safety and immunogenicity data and the lot-to-lot consistency clinical study. And I also want to briefly mention the way we determined our primary endpoint for those studies. We've determined this [ surrogate ] of protection using sero from individuals immunized in our Phase I clinical trial and transferred those sero to non-human primates. So we were able to transfer the antibodies built by immunization to non-human primates and have them challenged those nonhuman primates with wild-type chikungunya virus. And when we monitor the animals for development of disease and for viral titers, we were able to determine which antibody level pre-challenge was resulting in a non-detectable viral load after the challenge. And this cut of titer has been agreed with the FDA as our definition for seroresponse. Just in brief, that's the design of our Phase III clinical trial. We ran that study in the United States. We included adults above 18 years and above with no upper age limit. We've been enrolling around 4,100 individuals, about the 3080 received the VLA1553 vaccine and about 1,000 received the placebo immunization. The primary end point was on day 29 following the immunization and everybody was followed until month 6 in the trial. We looked at immunogenicity in a subgroup of about 460 participants. We've been able to report results from that study in the past. So what I'd like to focus on here for today is some new data that we've been able to generate in the October ACIP meeting on our vaccine candidate, there was considerable interest in data in older adults. So we've been looking at a new analysis population, a secondary analysis population from our trial where we were able to bring the number of elderly participants with immunogenicity data up to 107. And what we've seen there in terms of results is actually matching very nicely what we've seen in the primary analysis of that study. We see 99% of those aged 65 and older develop seroresponse in our study, and we also saw good persistence in that population. This slide is coming back to the results from our pivotal trial, but it's also highlighting the very exciting findings we've been able to publish on Monday on antibody persistence with our candidate. So I just want to walk you through the graph quickly. What you can see here to the left in the blue columns is results for the per protocol population in our pivotal trial with around 99% sero protections on day 29, so the primary end point, and if you look to the far right here, the purple column presents the seroresponse observed after 12 months in the recent date. And as you can see nicely seroresponse persists at 99% after 12 months, which is a really encouraging finding. This slide now shows you the development neutralizing antibody titers over time. So the kinetics. The population we're looking at here is the whole sample population of our antibody persistence study that's roughly around 360 individuals we were monitoring. And what we can see here is that as observed in the past, we see a peak neutralizing antibody titer at day 29 in our vaccine recipients. We see a slight decline up until month 6, but the titers stay comfortably above the level determined for seroresponse with the FDA. And then very importantly, now throughout the follow-up phase from month 6 to month 12, we see that the titers remain absolutely stable, which very nicely supports our prospects of inducing long-lasting immunity with a single dose. And then the other point I'd like to mention on that slide is you see actually 2 lines here. The blue color one is for younger adult, below 65 years of age. The darker maroon color represents adults 65 years and above. And as you can see, the lines are basically superimposed confirming that we see comparable titer levels in older adults and younger adults. And the reason why I'm highlighting that is not only because it's something that's not commonly observed with the vaccines, Oftentimes, you see lower immune responses in elderly individuals. But in our case, chikungunya also has a higher rate of causing severe disease in older adults. Just around our clinical data up. These are results from the lot-to-lot consistency trial. So lot-to-lot consistency trials are studies that are routinely asked from the FDA for development of vaccines to demonstrate that the vaccine can be manufactured consistently from lot-to-lot. And we have met the primary endpoint in that study. It's about 408 participants. The GMT values for the 3 lots tested match nicely and also the seroresponse rate observed in that study, 98% approximately match very nicely with the data we've seen in the pivotal clinical trial. That's a quick summary of our key clinical data highlights. I'm not going to work through all the points on immunogenicity because we mentioned both of those now. Just to briefly point out that we have seen also in our Phase I clinical study at an earlier time point of day 14, that neutralizing antibody titers had already developed in all the vaccines at that point in time. In terms of safety throughout our program, the vaccine has shown to be generally well tolerated. We see about 50% of the individuals will develop solicited systemic adverse events. The most common ones are headache, fever and -- sorry, headache, fatigue and myalgia. Most of the adverse events are mild or moderate intensity handful of severe adverse events have been reported about 2%, and that's most commonly fever. Now moving forward to more forward-looking slides. The first thing I want to highlight briefly is our collaboration with CEPI and Instituto Butantan. So CEPI has recognized the large unmet medical need around chikungunya vaccines and has therefore installed funding of chikungunya vaccines. And with -- in the framework of that CEPI funding, we have also entered a collaboration with Instituto Butantan who are an important Brazilian vaccine manufacturer. This collaboration will entail that Butantan will make the vaccine available manufacturer and also commercialize worldwide in LMIC markets, and we will also do some joint development steps. So what will be our next development steps in terms of ongoing clinical trials, the antibody persistence study that I've showed data with you previously, will continue with annual readouts for at least 5 years after immunization. And the second study that we're currently ongoing is a trial in Brazil in adolescents. This study is carried out in collaboration with Instituto Butantan, and the study will, on the one hand side, support an additional label expansion with the travelers markets for chikungunya -- for our chikungunya vaccine. On the other hand, we expect that the data from that study will be supportive for local licensure in Brazil. In terms of future clinical trials, we are considering co-vaccination studies of this vaccine candidate. We will further expand into other pediatric age subsets, and potentially do studies in special populations. And we also expect that under the accelerated approval pathway agreed with the FDA, we will be doing post-marketing effectiveness clinical trials in the form of Phase IV observational studies. On the regulatory outlook, we've been able to start submission of our BLA with the FDA in August of this year. We're looking forward to completing the rolling BLA submission in December. After we've completed our filing, there will be the FDA's review phase and at the end of the filing acceptance review phase, they will determine whether we are eligible for a priority review. We should be eligible based on the fact that we've been granted the breakthrough designation, and if they grant priority review, that will put us on a 6-month review clock. And the FDA will also determine the action due date at the end of their filing acceptance period. We may also see vaccines and related biologic to Products Advisory Committee meeting come up and the timing of such a meeting would be also determined in dependence of the action due date. Last not least, chikungunya has been a neglected tropical disease for a while and hence, the FDA has included chikungunya on their neglected tropical disease priority review out list, meaning the first the sponsor who will get the first approved BLA for chikungunya vaccine is eligible to receive a priority review voucher. And so should we receive the PRV, the intention of the company is to monetize that. Apart from our regulatory processes with the FDA. We've also received the priority medicines designation from the EMA and we expect to commence further regulatory processes, including with the EMA at the second half of next year. So thank you very much. And with that, I'll hand it over to John.

Good morning. My name is John Kanaras, I'm the General Manager for Valneva here in the U.S., and I'll be providing an update on our thinking and planning regarding the commercialization of VLA1553. Simply stated, it comes down to where we see this vaccine addressing the unmet medical need created by chikungunya. The COVID-19 pandemic has taught us help -- sorry -- has taught us how vulnerable we are to emerging infectious disease threats, especially those that originate outside our borders. And the WHO, along with many other public health organizations, have begun launching initiatives to mitigate the risk of diseases without breaking pandemic potential. The global arbovirus initiative that was launched back in March of this year. List chikungunya as 1 of these diseases that has outbreak potential, not pandemic because, it won't go there. The frequency and magnitude of outbreaks has been increasing globally over the past 20 years. And many times, that spark of an outbreak is initiated by a traveler, either within region of a country or across borders. As shared by my colleague, chikungunya has 2 distinct phases and is associated with significant morbidity and has both an acute and chronic phase. Of particular note, the chronic phase can last months and years and is often associated with chronic rheumatism that can be considerably disabling. While there's no seminal estimate of the cost both human and economic cost of chikungunya globally. There is one recent estimate by researchers out of Yale University that estimate the burden of chikungunya in the Americas. These researchers attempted to estimate the underreporting that happens with chikungunya during the outbreak and expansion of chikungunya between 2013 and 2015. Through their estimates, accounting for that under reporting, they projected that there were 39.9 million cases of chikungunya, 23.8 million disability-adjusted life years lost at a cost of $185 billion to society. The reason for this is the cycle of transmission, unlike respiratory diseases, where the cycle of transmission is primarily human to human. The cycle of transmission for chikungunya is almost exclusively vector to host. So as described previously, an infected mosquito, this is the urban cycle, an infected mosquito will bite a naive host. That host will become viremic than another mosquito bites that viremic hosts ingests the virus and then transmits that virus to another naive human continuing in the cycle. And that's what causes these acute and abrupt outbreaks. There are 2 primary vectors, and the geography for these vectors has expanded considerably over the past 2 decades. The Aedes aegypti vector was the original vector. you see on this graph, the vectors and their habitat. So in green, those geographies are not suitable for either vector and yellow is suitable for Aedes aegypti and blue for albopictus and then red suitable for both. So the Aedes aegypti mosquito was the originating mosquito, primarily habitat in tropical and subtropical regions. It originated in Africa and then in the early 2000s, spread to Asia. At the same time, there was a mutation in the virus that allowed it to then be able to be carried by the albopictus, and that's important because the habitat for the albopictus is broader. It goes into temperate climates and even colder climates. And then in about 2013, the virus was introduced into the Americas, specifically the Caribbean and spread from there. So at this point, there are over 100 countries where chikungunya has either been reported or is endemic and that impacts about 3.9 billion inhabitants. And so those inhabitants are clearly at risk for the disease. But equally importantly, travelers to those endemic areas are at risk for the disease. And given the cycle of transmission that we just described, what has happened and can happen is that an infected traveler can [ unwillingly ] come back and start local transmission in their geography. And so if we can zoom in on the U.S. and Europe right now, I'll share with you kind of what the habitat for these vectors are in the U.S. and Europe, specifically the top half of the slide looks at albopictus and where it's currently endemic. On the far -- my far right, your left, is the U.S., obviously. And then if you look at the your right in red is where albopictus has been established within Europe. The bottom half of the slide looks at aedes aegypti and where it's endemic in the U.S. and also limited establishment of aegypti within Europe at this point. And so again, the risk of outbreak is really linked to infected travelers coming back. And what we're advocating for and what we believe is an opportunity is to help protect the domestic public health security of each country by routinely vaccinating appropriate patients before they travel abroad, so they do not unwillingly bring back the virus and start local transmission. And both the U.S. CDC and ECDC monitor both imported cases and locally transmitted cases. So on your left, my right is data from the U.S. CDC. You see a spike in cases in 2013, '14, following the introduction in the Caribbean and then a pretty consistent trend of case reporting leading up into the pandemic when things kind of shut down. Similarly in Europe, you see a spike in cases during an outbreak in Italy and France, but a consistent flow of cases being observed within Europe, mainly imported cases. Fortunately, there haven't been many locally transmitted cases, but there's always the potential for that. And again, the rationale for advocating for policy to proactively vaccinate outbound travelers who are at risk for chikungunya. So that naturally flows to where we see the opportunities for this vaccine and where we think we can have an impact on the unmet medical need of this disease. So specifically within travelers, both civilian travelers going to CHIK endemic markets, military people who are deployed, active duty personnel and dependents deployed to CHIK endemic markets and then local procurement opportunities with governments who are preparing for potential outbreaks. Those are varied and a lot of competing priorities within government budgets for that, but it's -- those are discussions that are being had. And then on the left side -- your left side on my right, is the opportunity for having a big impact on the markets where chikungunya is currently endemic working with Butantan and CEPI to commercialize the vaccine in those endemic markets. Fortunately, VLA1553 fits perfectly within our existing commercial infrastructure. We have an experienced team of professionals who have tremendous depth of experience commercializing vaccines generally and travel vaccines specifically. This is pretty much a plug-and-play vaccine for us within our existing infrastructure. At the same time, there may be some additional resources needed depending on the market to fully capitalize on the opportunity for chikungunya. And -- but in the grand scheme of our overall plan, it's relatively modest in terms of the additional resources needed. Now one of the key issues with respect to the opportunity is how many outbound travelers are going to these CHIK endemic markets. These data are from IATA and they look at outbound passenger data from Valneva markets to CHIK endemic markets. Now these are passengers, not unique travelers. The easiest way to think about unique travelers is divided by 2. That's a factor that we usually get from IATA that accounts for unique travelers. And so what you see, 2 key points on the slide. Number 1 is the global travel recovery is beginning. We see it clearly in our commercial data. We see it in the IATA data. And IATA is projecting that the global travel recovery will be fully in place by 2025. That's point number one. Point number 2 is a small percentage of a large number, it's still a large number. And so we're not saying that every outbound unique traveler is appropriate for our vaccine. But even if we get just a small percentage of outbound travelers protected, that yields significantly doses sold and significant patients protected. This is new data regarding understanding the customer perspective on chikungunya disease and their likelihood to recommend or prescribe a vaccine [indiscernible] for the HCP or for the traveler to accept the vaccines. So let me warn you to the data. So first, we did two large-scale quantitative internet-based survey studies about a year ago with -- first with health care professionals globally and then with travelers globally. What you see on this slide are strictly the U.S. respondents. We ask them questions in a 5-point Likert scale. And what these data show for the as we expose both the HCPs and the travelers to a general summary of the chikungunya disease and the map of where it's endemic. And then we ask them these 2 questions. So for HCPs, we ask what is your likelihood of recommending a chikungunya vaccine if recommended by the ACIP. Now this was a generic chicken venue vaccine. This was not our target product profile. Just trying to understand what the interest is in the chikungunya vaccine candidate of HCP said they were very likely to recommend or prescribe and 73% said they were somewhat likely. So top 2 box score of 78%. For the travelers, we similarly ask them, if you're a doctor recommended chikungunya vaccine, again, a generic vaccine, not specifically our vaccine candidate, how likely are you to get vaccinated. And so 52% -- top box score was 52% in the top box score. And then somewhat likely, the second highest box was 29%. So a combined 79% top 2 box score. And so what we take this as is that there's considerable interest in the disease and the vaccine, if educated properly. But we also know that awareness is really low, and we've got a lot of work to do to educate both physicians and travelers. We've started that work this year with presence at many international congresses, and we'll continue that work into 2023. This is also new information. So the market access environment for travel vaccines has historically been primarily an out-of-pocket market where patients pay out of pocket and there's limited access due to affordability issues by patients. But that landscape is changing, specifically in the U.S. with the passage of the Inflation Reduction Act this summer. There was a component of the Inflation Reduction Act that requires that all ACIP-recommended vaccines, for patients enrolled in Part D plans will be covered without cost sharing. So even if used in limited populations, zero cost sharing, the industry lingo is first dollar coverage. So it's covered at $1. This is new. And so in the U.S., there's 49 million American 65 and older, an estimated 10,000 Americans turn 65 every day with the aging in of the baby boomer population, and we're really encouraged by this policy change because it clearly demonstrates the importance of vaccines, not just routine vaccines but all vaccines in protecting individuals. This policy is not only good for the individual, but again, it's important and good for our domestic public health security given the outbreak potential of chikungunya. Another really key point on this slide is that it anchors to an ACIP recommendation for coverage to be in place, it has to be recommended by the ACIP. And so that transitions to this next slide, which is the #1 priority we have in the U.S. is to work with the CDC to get a recommendation for this vaccine and appropriate individuals. And so the ACIP process is well known to us, we've been through it with IXIARO. As you all know, the CDC established the Work Group in May of this year. We had a joint presentation to the ACIP in October. And the CDC has declared an estimated date for a recommendation vote to be February 2024. So the bottom half of the slide is it comes from a CDC slide deck with their time line, superimposed over that is our regulatory -- expected regulatory time line. And so we're working really closely with the CDC to give them all the data they need to help them integrate the information so that they can make an appropriate recommendation for whom this vaccine should be recommended and in what circumstances, and should that recommendation come to be, then the information shared on the previous graph would -- previous slide would fall into place where individuals would have first dollar coverage for our chikungunya vaccine who are Medicare Part D. So in closing, just to summarize, chikungunya is a significant public health threat with significant morbidity, the habitat for the vectors has continued to expand, and there's a very real threat and potential for further expansion and even local transmission within markets like the U.S. And so we believe vaccinating travelers is a really important consideration for policymakers. This vaccine is -- fits in perfectly to our existing commercial infrastructure, and we believe that we've got the capability and expertise to maximize its potential and help to protect patients support HCPs and stakeholders and deliver value for our shareholders as well. So with that, I will turn it over to Thomas to talk to you about Lyme.

Thank you so much, John. Yes, let's turn over to Lyme disease. And you know that we are very excited about our Lyme vaccine program. In our collaboration with Pfizer, you know that this program is the only vaccine development program targeting Lyme disease in the world on the planet today. And we have gone through numerous clinical studies, Phase I, Phase II, and we are right now in Phase III with active enrollment ongoing. I mentioned the partnership with Pfizer. I'm going to explain more what the terms and conditions of this partnership look like. We have developed here a very modern recombinant subunit-based vaccine approach covering through a multivalent, 6 valent, to be precise the main serotypes prevalent in the Northern Hemisphere. And again, I'm going to go through those in detail. This vaccine follows a proven mode of action. There used to be a Lyme vaccine back in the '90s, here in the United States. This vaccine was, I would say, a development success by a public fiasco, and basically, we follow a similar scientific mode of action and therefore, have a high probability to reproduce also the respective effectiveness numbers that you've got to see. The program got Fast Track designation by U.S. FDA back in 2017. Our partnership with Pfizer at a glance here. So we established the strategic alliance with Pfizer back in April 2020. We amended and updated the agreement earlier this year. In the summer, we adjusted a couple of points due to the evolution of the partnership and also the evolution of, let's say, the development plan as part of the continuous regulatory interactions. We changed the cost-sharing split from 30/70 to 40/60. Pfizer invested $95 million in to Valneva and became one of our top 5 shareholders. And of course, this is a deal that gives Pfizer the full responsibility to for late-stage development as well as control over global commercialization. We are eligible to receive a bit more than $400 million in milestone payments. We received already $165 million. We have then later tiered royalties starting at 14% to 22% combined also with -- as I mentioned earlier, cumulative sales milestones as part of the $400 million bucket. Yes, and we have a wonderful core development structure in place, excellent working relationship. And I would say the best possible partner for this program you could find. Yes, Lyme disease. I mean, we are here in New York City. I don't think that I need to talk a lot about Lyme disease. It is a very severe tick transmitted infection. We see this really at a rise because we learned earlier about chikungunya vectors. Here, we are also talking about a vector transmitted disease. And of course, due to global warming and other implications, the tick population is at a rise and because the tick population is at a rise, the disease is at a rise, and we see here in the U.S., for example, a clear distribution, Lyme is everywhere. You can even find Lyme cases in California, but you see distribution from north to south, from east to west. And you have in Europe, you have some countries with high incidence rates of Lyme. It started all off in the so-called Alpine Belt, but then you now see that it's spreading and even countries where there was no Lyme disease in the past like France has a quite significant number of Lyme disease cases today. The -- it is very important to note that Lyme borreliosis can progress to serious life-altering symptoms. It starts with an early localized disease. The famous bullseye called erythema migrans, then the non-specific flu-like symptoms. It then progresses towards disseminated disease. This can take days, weeks or even months after the initial infection. And this includes things like neuroborreliosis, carditis, arthritis and other severe clinical manifestations. It's also important that the world has learned a lot about the clinical manifestations about Lyme disease. And what was considered a rather -- a need for -- back in the '90s, there was a paper -- people saying, the vaccine against Lyme diseases a vaccine for [ UPs ], right? I mean, nowadays, I mean, we have all learned that this is very, very different, and Lyme is very, very serious. And yes, and then there are persistent symptoms. And there is no -- literally no response to treatment and very long-lasting, sometimes up to lifelong clinical manifestations. The -- clearly, vaccination is a solution. And the prevention by a vaccine would be a significant improvement over current preventative treatment strategies. And the physical prevention strategies have limited effectiveness. As we all know, the antibody -- the antibiotic prophylaxis after the tick bite is effective for a certain period of time, but the bite is often unnoted. And the early disease may be missed, and then the diagnosis still today is a challenge and the potential for severe [indiscernible] manifestations is really, really huge. When it comes to the mode of action we are using and targeting the so-called outer surface protein A of Lyme borreliosis uses called OspA and this mechanism is basically a mechanism that takes place in the mid gut of the tick. So basically, when the tick sucks the blood from the human host, this blood contains anti-OspA antibodies. And those anti-OspA antibodies do the job in the mid gut of the ticket. Some of the mechanisms that really take place in the mid gut of the tick are understood, others not yet fully, right? So we know that clearly, the antibody to OspA neutralize bacteria in the midgut of the tick and blocking therefore, the transmission to the host back with the secretes that the tick gives after it attached to the human host. However, there are also mediated effective functions in the tick and those are, as I said, not fully understood at this point in time. When we talk about our vaccine design and the way we have structured this vaccine, I would call it modern protein engineering. What you see here is truncated, stabilized, lipidated, so-called heterodimers. So what does it all mean? It means that you target primarily the C terminal of the region containing the protective antibodies, the epitopes, and then you combine it pair wise, serotype 1 with serotype 2, serotype 3 with serotype 4, 5 with 6. You use a linker, which is basically derived from a certain number of amino acids from serotype 2 and stabilize it with a disulfide bond you lipidate it. So the lipidation together with [ L1 ] has an improvement in effect on positive immunogenicity. So it's a sort of an additional adjuvantation. And yes, and the interesting feature that we did, and we talk more about the old Lyme history is that we have replaced a region in serotype 1 that has -- when they sequenced back in the '90s, they saw that there was a region that had an [ neumology ] to a human T cell epitope. This is called hLFA-1, and replace that, which exists only in serotype 1 with a similar region from serotype 2. The old vaccines that were in development back in the '90s were as a full length, not only the C terminal, full length serotype 1 only. One license, LYMErix by GSK, Immulyme, Sanofi successfully conducted Phase III. After 3 immunizations, they showed 76% or 92% efficacy in a placebo-controlled setting. We worked, of course, before spending a lot of money together with Pfizer in late-stage development, we looked at proof-of-concept. So is there an animal model that can help us to predict where we're going to land on the effectiveness of the vaccine, and so we had only one data point. And the one data point was that the old vaccines, a serotype 1 full length worked. So we recooked it. And when you see here, the Lip-OspA is basically the native full-length OspA serotype 1. So in a way, the old LYMErix construct. And we did an active immunization to through the tick challenge model in mice, which mimics very nicely the overall mode of action because it takes place in the mid-gut of the tick, right? And we showed that VLA15 was as efficacious as the native full-length OspA, looking at serotype 1 only. And we did also a passive transfer model and showed also there that the human sera from people immunized with VLA2000 -- with VLA15 were protective. When we look at the development plan, I mentioned already one Phase I study, 3 Phase II studies, including pediatrics, more than 1,000 people pre-Phase III had received the vaccine candidate. We are now in Phase III. Enrollment is ongoing. And I'm going to talk more about the VALOR study in a minute. When we look at the key immunogenicity data that we obtained over the course of the last years, this is a very interesting and important slide. When you develop a multivalent vaccine, there are a couple of things that you want to have. Number one is you want to have a balanced immune response across the different serotypes. And this is something that we achieved through the various Phase II studies, so you see a very nice and balanced immunological profile against the 6 serotypes. Second, you want to say that -- you want to see that, of course, you have an antibody uptake. You see the immune response going up and staying up for the protection targeted across the tick season. And then since we know from the old Lyme vaccines that a booster will be necessary. You want to see the anamnestic response. So what happens if you give a booster shot? And this is shown here on the red bar, and you see that after a booster shot, the immune response goes significantly higher as compared to primary immunization. So a fantastic anamnestic response, and whether a booster every year is needed or a booster every other year, every third year, this is something that we have to show as part of the further development. Safety, not a lot to say, bottom line message generally well tolerated and very, very consistent with other licensed lipidated vaccines. When we look at the 6-month antibody persistence results that we recently kind of presented, this was another very important point because also here, we saw that the antibody levels remained above the baseline 6 months after completion of the 3 dose priming. We saw that the higher antibody levels observed in the 3 dose versus the 2 dose, where -- which again, gave us a validation of our decision to go for the 3 dose priming. And we confirmed the safety profile that we saw in the past. So how does the current study look like that we are currently running? 6,000 people U.S./Europe. So randomized 1:1, placebo against [indiscernible], randomized 2:1, U.S. versus Europe. -- primary endpoint, and this is -- this was something that we had to change after regulatory consultations, primary endpoint, efficacy after 3 plus 1, so 3 dose priming plus a booster for the second season. So the study goes over 2 seasons. And then we look at the primary endpoint efficacy after booster in the second season. And as a secondary endpoint, the efficacy number after the first season. This study is called VALOR, currently actively recruiting and we are targeting completion of course, in time for the tick season 2023. And with that, I close the part on Lyme and with just 1 word on Lyme. We are very, very excited about the fact that we are working towards finding a vaccine preventable solution for such a devastating disease. And we really hope that we will be able to successfully complete this program on time with hopefully a positive data readout at the end of the tick season 2024 and then a submission for licensure in 2025. Yes. But with 2 very exciting programs like our Lyme and CHIK programs in late-stage development or even in the licensure process already in the case of CHIK. And with COVID that has been a great development success for Valneva but unfortunately not turned into a commercial success. We have to ask ourselves what's next in the pipeline. We consider ourselves a vaccine powerhouse that is able to bring products from bench to licensure. So therefore, the key question is how do we generate more programs in our clinical pipeline? And as I mentioned at the beginning, due to the fact that we redirected resources to COVID, we had kind of slowed down our preclinical activities. So we ramped it up. And we are trying to do a combination of bringing our preclinical programs forward, re-prioritizing our resources onto clinic -- onto preclinical activities, but at the same time, we will continue, as we have done in the past, to look for outside opportunities to potentially even in license earlier-stage clinical assets. When we look at our own pipeline, the important thing to note here is that we have 4 programs in our preclinical pipeline. And I'm not counting here what we discussed earlier, for example, with regards to Zika. Zika was already in the clinic, we may reactivate bring it back into the clinic. Here, we are talking about really things that we developed from bench onwards. And the most advanced program that we have is a program targeting the Human metapneumovirus. Commercially, and I'm very glad that Anders is here today, who is heading up our preclinical activities to present this more. But especially the potential combination, hMPV and RSV is expected to really tackle a very significant unmet medical need. EBV vaccine candidate against the Epstein-Barr virus. Very recently, again, a significant learning around EBV and primary and secondary mechanisms that vaccination against EBV could result in. We have been working on parvovirus and on Campylobacter. And to some of the questions that I received earlier, and I think we had -- with Peter had the conversation outside over coffee. No, we are not targeting only travel vaccines in our development. We are targeting areas of high unmet medical need. And with the exception of mRNA, this company has R&D capability and expertise across all different vaccine technologies that are out there. And I think this is a very important point to consider when we also look about into our preclinical activities. And with that, a little introduction to our future pipeline development. I would like to hand over to Anders.

Good morning, everyone. So I'd like to start to talk about respiratory infections in general for a minute. So respiratory infections, of course, affect all of us, right? On a fairly regular basis, at least annually, and the severity ranges from just a simple annoyance to being in bed for a few days. And for the most of us don't care which virus infects us, right? Because it's not really that important. But for some patient populations or some populations, they're very, very young, they're immunocompromised or they're elderly some of these infections can be fatal threats. And one of the most well-known, which is in the news currently is RSV. RSV has been the plague for decades or it had been a known plague for decades. And this is an especially bad season, which might have seen in the news. There are several states there are no pediatric emergency or pediatric intensive care unit beds available because of RSV. Good news is that after a very long unit towards an RSV vaccine, there were a couple of top line results reported by GSK and Pfizer in the past couple of months. And it seems, of course, I'm not pivot to the details, but it seems from the top line data that RSV vaccines are underway and will soon be available to prevent this terrible infection. So this begs the question, what comes next in the respiratory infection space, and also what lessons were learned from the long RSV development that we can apply to other infections. And the answer to the first question, we believe it's Human metapneumovirus, as Thomas mentioned, hMPV, for short. hMPV is very similar to RSV, both on the biological level. as well as in terms of epidemiology and disease burden. It might be a touch less severe, but it's nevertheless a significant threat to the same population as RSV is, for the very, very young and for the elderly. And it's a great number of people in the hospital every year. So there is, of course, no hMPV vaccine. And we are planning to develop a vaccine based on a protein subunit, which I'll talk about in a minute. It has a large market potential. And as Thomas mentioned, it has a potential for combining with RSV or other vaccines. This is the current development landscape. So Moderna has actually completed a Phase I. Icosavax have just started the Phase I and then ourselves and the NIH have preclinical programs in advanced preclinical stage, I would say. There's a few things worth noting here, and that is the -- that both the Moderna and Icosavax candidates are already bivalent. So they are combining either hMPV with parainfluenza virus in the case of Moderna or hMPV and RSV in the case of Icosavax, which shows the great potential for pairing these up. And another important factor note is that Moderna has chosen a full-length F protein. And I'll get back to that in a minute, but this is important. But it's a way for now, the Moderna is not an engineered stabilized antigen, which I will talk about a lot in a minute. The other 3 approaches, including ours, is -- are stabilized. So Moderna has posted their data or publish the data, and they reported a sixfold boost in previously exposed adults, which -- and this was not dose dependent. It was constant over the dose range they tested. It is, of course, very hard to know without the cordial protection, but the sixfold boost really means, whether this is a significant increase or not. But again, comparing to RSV, a similar virus albeit different virus. The NIH and Pfizer have posted higher boosts for their RSV vaccines, and take it for where it's worth, but it's hinting that there's a room for improvement for this -- compared to the Moderna vaccine candidate. The other question I posed in the first slide was what lessons can we learn from the RSV success and apply it to hMPV? And the clear answer is structure-based antigen design. So the RSV vaccine were to truly enable the RSV vaccine and got this to the finish line, most likely, was the application of structure-based design and the discovery first of the RSV F pre-fusion structure, which allows scientists to stabilize it, and uses as an antigen in the vaccines where the previous post-fusion structures had failed. Why isn't subordinate shown in this cartoon, so from left to right, you have first the pre-fusion structure, which is sitting on the virus surface. When the virus comes in contact with receptors on the cell surface for entering the host cell, it goes through a large confirmational change. First, it inserts to fusion peptides or fusion peptides, -- into the cell membrane. This confirmational change continues as a giant engine, if you will and brings the 2 memories together, fuses the lipid membranes so the virus can enter the cell. And the end result is that you have a post-fusion structure, which is basically the spend molecules. It's no longer active. And whether you have epitopes exposed on postfusion structure or not is sort of irrelevant because that just bind but it doesn't prevent anything. So what you really want is antibodies to target the pre-fusion structure and can prevent either the attachment to the cell or is confirmational change. So our -- and this is what was enabled with the RSV vaccine and brought this to the goal line. So our hMPV vaccine is based on these principles. So we have a stabilized pre-fusion F antigen. F is immunodominant and highly conserved as it is for RSV. The desired immune response is a high level of neutralizing antibodies, biased towards TH2, so this is a type of T cells -- sorry, you want to avoid tissues. Biased towards TH1. You want to avoid TH2, because TH2 T cells or TS2 biased responses have been shown to [indiscernible] increased risk of vaccine-enhanced disease for RSV and also for SARS-CoV1, but not for 2. Just like RSV, there are 2 subtypes of HMPV A and B. And of course, you want to vaccine to protect against both. The approach we have taken is the same as for the 2 RSV vaccines I mentioned, subunit protein. We will and we are looking at adding an adjuvant whether it's needed in the end we'll see or we at least assuming this is the case. And again, there is potential for combining this vaccine because it's the same technology with other RSV -- or with RSV vaccines. This slide outlines how it came to our pre-fusion antigen. And I can't go into details because the method, I think, is a trade secret and the details of the design are not yet public. But in a simple way, you start with the structural information available. So the RSV pre-fusion structure at the time, there was, of course, a sequence for hMPV and you can do simulations to model the hMPV structure. Based on the simulations, you can then design modifications to stabilize this protein or fix it in a pre-fusion form, you test these experimentally. And you use the data that company's experiments to feed back and go over this a few times. And in the end, you have, in our case, a pre-fusion F protein. There is not an hMPV pre-fusion structure known. It was not at the time. Characterization shown on the right-hand side, it's fairly simple in this research stage, you look at purity and yield by standard methods, you look at the trimer composition. So the native F protein is a trimer, which is, of course, important for have the right confirmation. You look at the higher trimer content. But the most, of course, important is you can use pre- and post-fusion specific antibodies to show that it's binding pre-fusion specific antibodies but not post-fusion specific antibodies, to have a high likelihood that this is in the right confirmation. We are currently developing -- we are currently determining the [indiscernible] and crystal structures of our F antigen, data is not yet available, but that is something that's ongoing. It will be the final proof that we have the real thing. Of course, we've also shown immunogenicity, and this is also something we did in these iterations. For the final candidate, we have done mouse immunogenicity in challenge studies. Mice were immunized with either a pre-fusion F protein based on the A1 strain or a B1 strain, or A1 strain or a B1 strain. There's several. And then challenged with the subgroup A2 virus. We determined neutralizing titers against A1 and B1 and we also challenged the animals with the A2 virus and looked at the viral loads in lungs of these animals after challenge. So the left-hand panel, you see the neutralization of A1 subtype virus. And as you can see, the A1 vaccine, not surprisingly, induced higher titers against the A1 virus than the B1 strain vaccine. What was surprising was in a different experiment. We showed that the A1 vaccine also induced higher titers against B1 virus for neutralization. And finally, in the right-hand panel, as say a challenge study here, here small bars are good. And you can see that for the A1 virus, we have really small -- low dose levels, already complete protection against viral application in the lung. So the A1 strain is better than the B1 strain as a vaccine antigen also against heterologous subtypes. So to summarize hMPV part, our proprietary hMPV vaccine candidate is based on an adjuvanted subunit stabilized pre-fusion F protein. The stabilized pre-fusion F candidate is ours. We have developed it from scratch. And I would say it's cutting edge in terms of being innovative. It is produced in CHO cells, which is a standard vaccine production platform. So there's nothing -- there's no challenges there. And the purification process is also based on standard methods, and we have production yields that are suitable for product for larger-scale production and upscaling. Immunization with the pre-fusion A1 F protein generated superior neutralizing antibody responses against both homologous and heterologous strains and also the challenge -- it protected well against challenge alert low doses. And as I mentioned, adjuvant, evaluation is in progress, and we have some promising results. Switching now to the other program that Thomas mentioned, EBV, Epstein-Barr Virus. This is not a respiratory infection. It is a herpes virus. Most of us are infected with it when we get to adulthood, 95% or so by the age of 25. It stays with a host for life. You most likely know EBV for its -- as being a causative agent of infectious mononucleosis, also known as mono or kissing disease. It's a fairly severe febrile infection [indiscernible] and out of commission for a few weeks at minimum. It has a big impact on job time lost, students being out of school for a long time and for the armed services. But it's actually, in the long run, probably more significant from medical perspective and from a public health perspective is that it's a causative agent for infectious -- for multiple sclerosis. This was a landmark paper that was published early this year, although there had been interim analyses previously, so this was not a great surprise. But the paper this year from Björnevik et al made a very, very strong link between multiple sclerosis and prior EBV infection and mononucleosis. And also it's been known for decades that EBV is associated with human cancers of several different kinds. EBV was first isolated from a cancer cell, so this is -- it was the first isolated oncovirus, as a matter of fact. A few words about the infectious cycle of EBV because this has become important understanding where we are thinking of our vaccine development. EBV enters the host usually through the mouth and infects epithelial cells in the oropharynx. And from there, there's a secondary spread to B cells. And then they can -- of course, they set up latency in B cells, and the virus can then reactivate periodically and reinfect epithelials, et cetera. The B cells are required for -- the B cell infection is required for infectious mononucleosis as well as the -- likely for multiple sclerosis. The epithelial cells are important. If you want to have sterilizing immunity, you need to prevent the initial infection. And of course, epithelial cells is also important in several of the human cancers. The reason I'm telling you this is that the different antigens we're looking at for EBV elicit antibodies that block either infection of epithelial cells or infection of B cells or both, and that's where it becomes important. Similar to the Lyme case, there has been a significant clinical trial made in the past by GSK that kind of guides our thinking on this and also provides a proof of concept, to an extent. So GSK had a gp350, a subunit protein vaccine adjuvant with AS04, which went to a Phase II in the early 2000s. And shown in this table, you can see a protection data, and it shows that you had a statistically significant 78% reduction of mononucleosis in this patient population, but no protection against infection itself. In hindsight, this was not surprising because the gp350 protein elicits antibodies that only block B cell infection. So in a sense, this vaccine did exactly what it did. It elicited these antibodies that prevented a B cell infection, which prevented the mononucleosis disease, but it was not a sterilizing immunity because the host can still get infected through the epithelial cells. So for our second generation EBV vaccines, ourselves and other developers, are including additional antigens, which will elicit antibodies that also block infection of epithelial cell infection. This is a look at the landscape for EBV. Moderna, again, it's always Moderna, are already in Phase I. They have 2 antigens called GP220 and gH/gL/gp42. gp220 is a variant of gp350. The name is a bit misleading, but it's a splice variant. So it has the same epitopes as gp350. gH/gL/gp42 is, of course, a tripartite complex that's a variation gH/gL. NIH have their own program, which is based on ferritin nanoparticles, which is one of their platform technologies. They are actually in the clinic already with only gp350, which, as I just told you, will likely not work as well as is needed. But they have also out-licensed the technology to a company called ModeX. And ModeX have published non-human primate data where they have also this gH/gL with and without gp42. And it seems likely this is what will become from NIH and MODEX, the final formulation. And they have published a guidance that they will enter the clinic next year. And then there's our own program. And we are looking at 3 antigens, the gp350, again, gH/gL and gB. gB is the EBV version of F. So it's the fusion protein. We think that antibodies of gB has the potential to block infection of any cell type, which we find highly intriguing. We have 2 paths. We're doing our own development with our own designs, and we also have an exclusive evaluation of a third-party designs. A few words, so this ties back again to the RSV story. We have taken a rational approach in this. There is structural information for all of these 3 antigens. So from left to right, it's gp350, gH/gL and gB. Not shown here, there's also gH/gL/gp42 structure available. So we have all the information, and we are -- we have already designed a large number of antigens we are currently testing. Of course, this is very confidential, so I cannot go into the details. And -- but they range from minor tweaks that will help with productivity, increase production yields, et cetera, to the other end of spectrum, where we have more significant innovation, where we think we were able to improve the immunogenicity of these proteins compared to the wild-type version. As I mentioned, we have -- this is our own internal design process. We have also an exclusive license agreement where we are evaluating designs that are of slightly different nature in parallel. And these 2 programs are complementary. But in the end, we will basically pick the best antigen combination from either of the programs to take to the clinic. So to summarize here, neutralizing antibodies block EBV infection of B cells and epithelial cells. Our vaccine candidate will be based on adjuvented, subunit viral glycoproteins that would elicit high titers of EBV neutralizing antibodies, and neutralizing both B cells and epithelial cells. We are evaluating both external and internal designs. And we will again combine the best antigens from either of these approaches. This is, again, subunit protein technology, can be easily produced in CHO cells and scalable to whatever quantity we need and purified using standard methods. And again, we will use modern or novel adjuvant technologies to maximize the immune response to these antigens. This is also plans that are drawn out, but this has to come after the antigen selection. With that, I hand over to Peter.

Thank you, Anders. So now let's look a bit at our commercial product proposition. Right now, we're selling 2 of our proprietary products, and we have a couple of products that we in-license from third parties. The first proprietary product is IXIARO, a product against Japanese encephalitis that we sell in the [indiscernible] markets where we have a direct presence, and you see them listed here, so U.S.A., Canada, U.K., France, Nordics, the Benelux countries and Austria. And then we have -- we also sell it through partners in specific other key markets, for instance, Germany. IXIARO generated about EUR 100 million revenues prior to the pandemic, and they actually delivered double-digit sales growth at least for the last 3 years prior to the pandemic. Second product we distribute is DUKORAL. DUKORAL is a product against cholera and against ETEC in certain countries, which delivered about EUR 30 million in sales prior to COVID. And again, we distributed in the markets where we have a direct presence. Here, the key difference is -- to IXIARO is that we do not sell DUKORAL currently in the United States. So those are the 2 products -- 2 of our own products. And then as you see at the bottom of the slide, we have a number of products we in-licensed from third parties in specific markets. So it started in 2016 when we in-licensed a product against flu for the Austrian market, followed in 2018 by rabbies product for Canada. And then in 2020, 2 products that we in-licensed from Bavarian Nordics. And finally, we announced earlier this year a deal for distribution of VBI's hepatitis B product in European markets. So you see, we have a really good track record here where from 2016 to date, we in-licensed a quite a number of products. And in the first 9 months of the current year, we generated approximately EUR 18 million in revenues. Now looking at the commercial performance and the sales performance and how it developed once the pandemic hit. So what you see here is we sold approximately EUR 130 million of products pre-pandemic, which then, of course, dramatically collapsed as the pandemic hit, and it was basically divided by 2 in 2020 and 2021. Now looking at 2022, we actually see a nice recovery of the travel market, in particular, for IXIARO, but also for DUKORAL. And then what you see also here in the chart very nicely illustrated is the significant growth, of course, of the third-party products. So we announced earlier this year that we expect to achieve EUR 70 million to EUR 80 million product sales this year for our existing travel franchise, of course, significantly driven by the third-party products as well. And then we clearly -- the way we look at it is we clearly see a significant recovery again in 2023. And then by '24, we expect to be back at pre-COVID levels. That, of course, always provided there is not, again, a major wave of COVID-19 pandemic. Actually, as we ramped up sales in the current year, we also experienced some supply shortages with both IXIARO and DUKORAL, and we expect to recover these shortages in 2023. Looking at our first 9 months performance, and we presented this to the market about a month ago. So we see IXIARO delivering EUR 19.4 million growth -- sales, sorry, significant growth over last year, about 4x the revenues of 2021, and that is the travel market, so excluding the DoD. We see cholera -- the cholera product, DUKORAL as well nicely growing to EUR 9.2 million, where, in the prior year, we had almost no sales, EUR 0.5 million sales only. And then as I already mentioned, third-party products increasingly significantly -- increasing significantly. You see the U.S. Department of sales -- Defense sales are down, and that was expected based on the delivery schedule. And here, we expect a new supply contract in 2023. Now a few words on our COVID-19 vaccine sales. As Thomas already mentioned, we really think it was a huge development success. But unfortunately, it did not result in a commercial success. And we generated a year-to-date sales of EUR 23.9 million at the end of September. That was driven by shipments to the EU member states that maintained a certain number of doses and also to the Kingdom of Bahrain. Now how do we expect to execute on our commercial strategy? And we basically identified 3 key levers to accelerate commercial performance again. The first pillar here is the recovery of the travel health market. So as people start traveling again, we will continue to build on our brand identity and our reputation as a company that is really committed to collaborate and partner with health care practitioners and travelers to provide vaccines to travelers. We are providing tools and services to the health care practitioners and will, of course, support the customers as we see the market recovering. The second pillar is expanding our vaccine portfolio. And here, it's, of course, as I alluded to, adding third-party distribution products, but we would -- and we are, of course, continuously looking for complementary partnerships. And then the third pillar, and John talked quite a bit about that, is the launch of our chikungunya vaccine expected in the United States in 2023. So we are, right now, of course, building our commercial capabilities and infrastructure to really make that launch a success. We invested in market access capabilities also in-house. And we develop, of course, the brand and are continuing to invest into better understanding the market. On this slide, you see an illustration how we roll out our new travel health campaign, so this is basically what we will provide to the doctors to support our unique travel vaccine range. And it basically highlights our strong R&D capabilities and our commitment to the travel market. Now before we move on to the financials, I need to spend a few words, I think, on our COVID-19 vaccine. Again, given the lack of commercial success, we decided to suspend the manufacturing in the third quarter of 2022, but we will continue to execute on certain clinical trials that had started previously. And those -- some of those will run also into 2023. As Thomas mentioned, we have quite significant stock of 8 million to 10 million doses that are available for sales. And we, of course, continue our efforts to try and deploy those into international markets. We have discussions with various governments around the world. But right now, we do not include anything in our internal forecast related to that product. So anything we would sell would come as an upside. And we have some time, of course, because, right now, we have a shelf life of 18 months, and we expect to be able to extend that to 24 months. Now spending a few minutes on financial overview. So as you know, we listed the company on NASDAQ in May of last year. And then we did 2 successful follow-on offerings that actually generated good cash inflows. And then also, as previously explained, Pfizer invested $95 million into Valneva to support actually our contribution to the Lyme trial. So at the end of September, we had a cash position of EUR 260 million. And through the global offering, we added close to EUR 100 million net to that position. So the way we look at it is we're really well financed at least to 2024 to execute on our current business. Now given the COVID wind-down, we also went into a program that we called reshape, which is really looking into how we optimize our company to ensure our continued growth and deliver on our programs. So we are reducing our workforce, because we significantly increased the workforce because of the COVID program. And the way we look at it is we will decrease by about 20% to 25% our number of FTEs, and that will be done through a combination of natural attrition, but there will also be layoffs in 2022, but also again in 2023 as we wind down the programs. And we expect an annual saving of approximately EUR 12 million. Now as we focus on the future, we will clearly be a more nimble company post restructuring, but we will still be -- our headcount will still be about 25% above pre-COVID, which really positions us well to retain our talent and deliver on our programs. With the resizing of the company, we will, of course, continue to advance our chikungunya vaccine, invest in our Lyme disease vaccine together with Pfizer. And then, of course, also, as Anders alluded to, progress our preclinical assets. Now when we look at the equity story and how we expect to generate value over the coming years, as you see illustrated on this slide, today, our revenues are basically composed by IXIARO, DUKORAL and the third-party products. In 2023 and 2024, we will add our chikungunya program, VLA1553 to that, which would -- which we expect to significantly add to our top line. Of course, not so much in '23 because this will be the year of launch in the U.S., but apart from 2024. And then after that, the next step will be VLA15. Once it's launched into the market, we will get significant milestones for the first initial sales and then, of course, also generate, as discussed previously, double-digit royalties, with basically no spend attached to it. So we really see here a clear trajectory for growth and dramatically increase our top line. Before I conclude, I'll just remind you the related guidance we issued -- or we reconfirmed when we released our Q3 financials. So we expect total revenues for the year to be in the range of EUR 340 million to EUR 360 million composed of EUR 30 million to EUR 40 million revenues related to our COVID vaccine product sales, EUR 70 million to 80 million of our travel vaccines and then approximately EUR 240 million of revenues that are primarily driven by revenues recognized from the EC and the U.K. COVID contract. In terms of R&D spend, we expect quite a bit lower spend than we initially planned for. And so basically, what we guided is EUR 95 million to EUR 110 million, and we maintain that for now. So this concludes my section, and I think we're going to hand -- pass into Q&A, and I would ask my colleagues to join me up here. And Josh, you will moderate the Q&A, right?

While the panel is assembling, I'll just remind our webcast listeners that if you want to ask a question, you can submit your question via the text box in the webcast player or by e-mailing questions to questions@lifesciadvisors.com. We can take our first question.

Evan Wang from Guggenheim. Just interested, thank you for the presentation, very helpful, in terms of the chikungunya program, you highlighted a potential for a VRBPAC meeting. Is that based on any recent feedback from FDA? And if so, any additional that the FDA is looking for?

Does the microphone work?

Yes.

Excellent. So indeed, that expectation is based on FDA communications that we have had. And as I mentioned in the presentation, we're looking forward to receive more information from the FDA, including a potential date for an advisory committee meeting. And we believe that this will be determined only later once we're clear on the actual due date from the FDA side.

Got it. And then you've talked about some potential for in-licensing deals. Can you help us think about how Valneva is thinking about the type of deal? In terms of staging, what kind of validation you guys are looking for size?

I think you are referring to the -- what I mentioned around pipeline. Am I right? Yes -- so yes, I mean, you have seen that we have really strong R&D capabilities from early research all the way to bringing product to licensure. We have capacity in, I would say, earlier clinical stage programs. We have a very good, very solid and extremely strong preclinical pipeline, but we lag a little bit the earlier-stage clinical part. So we are currently looking into potentially augmenting this clinical pipeline. We have a process ongoing. We have a dedicated team ongoing that is screening the market at this point in time. Please keep in mind that the principles of what I explained around Valneva's basic mission will apply all of our assets, whether you look at the commercial assets or whether you look at our development assets, our highly differentiated assets, first-in-class, only-in-class, best-in-class. And this is clearly the direction of travel we've got to take. We're not going to go into the me-too space. We're not going to work on the 20th [ novel program ] or flu program. And we're not going to go into the ring with the big gorillas, so -- which means we're going to find -- we're going to screen for programs. And today, we have not limited ourselves to how we're going to finance it or -- so we believe that science will win. And we will look at the quality of the respective asset. And then we will take a decision how to bring it on board. We have a very, very strong shareholder base. We have extremely strong financial partners with whom we are working together for a long time. And we are convinced that if the asset is right, we will be able to finance it.

Other questions? I could take one question. Yes.

Just curious on the Lyme vaccine. Obviously, I live just North of Manhattan in the countryside, and Lyme is right there. And I know the population that surrounds me. And persuading them to take 3 doses of a Lyme vaccine, I know, would be difficult. They probably do 1. They may do 2, but 3 would be difficult for them. And then if it was annual, that also probably would be difficult for them. They would say, why do I need to get it? And I'm just wondering whether you've thought about starting some kind of program on an oral version of the Lyme vaccine, which would persuade them to do it because it's much easier. And was that not possible?

It's an excellent question, and the answer is not yet. So I think, on the one hand side, you are right. The more doses you have for priming, the more issues you are facing with compliance on the second or third dose, in particular. Having said that, we have many vaccines in the market today, which are based on a 3-dose priming and which are very successfully being, I would say, applied in the market field. Of course, it all depends around the balance of severity of the disease, the power of protection. And therefore, the recommendation will be key. The final efficacy number would be key. We are less concerned about a booster after the first season, especially since we have all experienced the COVID situation, the -- and it was a reason for why actually the FDA also wanted to see the efficacy data post booster because we ought to understand that there is a clear lack of evidence for COVID, for example, what really happens effectively from a fixing perspective post COVID. So we are less concerned about this booster. And whether then an annual booster will be needed or not, we have to see because, right now, you have seen that there is a very high anamnestic response. And whether the -- I would say the antibody persistence will be good enough after the first booster to potentially last for another 2 or 3 years, as it was the case initially for tick-borne encephalitis when it was introduced, we have to examine. And then as part of life cycle management in vaccines, I mean, we talked about this before, you know that. I mean, routes of application, routes of delivery, different ways of, I would say, applying the vaccine antigen is certainly something that all vaccine companies constantly are working on, but mostly in -- as part of life cycle management. And this is also how we look at it.

Alex Osipov, Cowen. Thanks for the presentation. I also had a question about the Lyme vaccine. Obviously, recognizing this isn't part of the development strategy currently, but was wondering if you think, in theory, there's an avenue for this mechanism of action to be efficacious against Borrelia already in the patients, in other words, for existing Lyme patients.

Yes, it's an interesting question. It's currently not in our focus.

[ Kyle ] from Oppenheimer. Congrats on the data yesterday again. So a good -- do you mind sharing more color on sort of the launch plan of chikungunya, considering both FDA approval process and also ACIP?

John, do you want to take it?