Hi, welcome to the 45th Annual TD Cowen Healthcare Conference. My name is Jackie Kiesa, and I'm an analyst here at TD Cowen covering life science tools. Now, today I have the pleasure of introducing Thomas Lingelbach, CEO of Valneva, who will be covering the mission and story of their specialty vaccine company. Whenever you're ready, I'll hand it over to you.
Thank you so much. It's a pleasure for me to present Valneva today. Yeah, Valneva is a leading specialty vaccine company. We are focusing on the development, manufacturing, and commercialization of prophylactic vaccines for infectious diseases in areas of high unmet medical need. We have proven expertise in the field. We brought three vaccines from bench to licensure in our history. We are focusing our commercial business on travel vaccination and travel vaccines. On the R&D side, as part of our fully integrated model, we are advancing programs that could deliver vaccine solutions being either first, only, or best in class. It's also worth noting that Valneva is a company that is technology agnostic. We have experience across the vast majority of the vaccine modalities. Our lead program today is a vaccine against Lyme disease, most advanced in the world today, partnered with Pfizer.
We are going to see a first phase III readout by the end of this year. As such, this represents a major catalyst for the company and hopefully our shareholders too. Our commercial business has been marked by continuous growth, except the COVID period where, of course, travel vaccination was literally down. We reported last year more than EUR 160 million in product sales. We have guided the market towards EUR 170 million-EUR 180 million sales this year, which would present a double-digit growth. The company had a strong cash position at year-end with almost EUR 170 million cash in hand. The current strategy of the company is geared towards targeting a profitable value proposition on the back of a successful Lyme introduction in the market, which is anticipated towards the latter part of 2027.
When we look at our portfolio, you see on top our three commercial travel vaccines. IXIARO is a vaccine against Japanese encephalitis. It's the only vaccine approved for this indication in the respective regulatory jurisdictions. We have a vaccine against cholera, which is in some markets also a label against LT-positive ETEC. The vaccine is well established for many, many years and distributed in and approved in more than 30 countries. We developed the world's first and approved chikungunya vaccine, which got licensed by now in the United States, Europe, U.K., and Canada. We just recently got the label extended by positive CHMP opinion for everyone above 12 years of age. I will present more about the ongoing development activities in the field.
When we then look at the R&D pipeline, as I said, the most clinically advanced Lyme vaccine program worldwide in an area of huge unmet medical need. We, of course, need to continue focusing on chikungunya. We are developing this vaccine also for children, for example. We have other activities such as phase IV effectiveness surveillance ongoing. We recently, second half of last year, brought an additional program into our pipeline, namely the most advanced and one of the clear leading tetravalent programs against shigellosis. It's a program that is right now in phase II-B. In parallel, while a phase II-B through a human infection model is ongoing, we have also a phase II in pediatrics that has or is about to commence. We are the only company in the world right now with an active clinical stage vaccine candidate against Zika.
Our preclinical pipeline is focused on two major indications, one EBV, and the second one is around the field of enteric diseases where we are working right now on a broad covering ETEC vaccine candidate amongst other enteric programs early stage. Let's focus a little bit on Lyme and Lyme disease. Of course, Lyme disease represents a major medical need, enhanced market opportunity. There is currently no preventative solution against Lyme disease, and also the treatment options are limited in nature. When we look at where is Lyme endemic, around 80 million people here in the United States live in areas where you have a high-risk exposure to Lyme disease. Around 200 million people live in Europe. That gives you an idea about the potential market opportunity for a preventative solution against Lyme disease. Our partner, Pfizer, is communicating the market opportunity well above $1 billion.
When we look at the case numbers, of course, Lyme disease is a vector transmitted disease. Due to global warming, you see a continuous rise of Lyme cases throughout the northern hemisphere. It is pretty severe. It is still heavily underreported every year. Last numbers from CDC show around about 500,000 cases in the United States, but certainly, and also as CDC admit, heavily underreported. When we look at the severity of Lyme disease, there are many clinical manifestations associated with Lyme disease, 10%-30% of all the cases develop in really severe progression, Lyme carditis, neuroborreliosis, or arthritis, just to name three and 5%-10% develop really persistent symptoms with long-term sequelae. This is really indicating that a prophylactic vaccine would represent a huge opportunity from a health economical perspective.
We have developed a vaccine that is suitable for people living and going to both sides of the Atlantic. Therefore, we had to develop a multivalent vaccine covering the six most prevalent Borrelia serotypes prevalent in the northern hemisphere. It follows an established mode of action targeting the outer surface protein A of Lyme borreliosis. It's a U.S. FDA Fast Track designated program. Right now, we are in the third year of multi-year phase III placebo-controlled field efficacy study. As mentioned earlier, this program has been exclusively partnered with Pfizer. We have received upfront payments when we started the co-development with Pfizer. We have future milestones up to $400 million still in total to be seen. Later tiered royalties, 14%-22%, depending on the level of sales. We are on track to see the first data readout by the end of this year.
We will see more data, of course, as we go into 2026 and anticipate the filing in 2026 simultaneously in the United States and Europe. It is also worth noting that Valneva completed its cost contributions to the shared development cost structure. We reported continuously other data, including antibody persistence data, for example. When we look at the phase III design, you see here this is also it's operationally split into cohorts. It's one study, placebo-controlled randomized one-to-one vaccine against placebo. We are testing not only the efficacy after the priming, which is a three-dose priming, but also the efficacy of a booster, given that it's highly likely that this vaccine will require an annual booster shot.
When you look at the color of the small syringes on the slide, you see that cohort one completed its primary vaccination as well as the booster, and the second cohort completed the primary vaccination. We are now in tick season, or we are about to commence tick season 2025. Hence, at the end of tick season 2025, we will see the readout across this very important study. Additional points to consider in this study, which includes more than 9,000 people, is, as I said already, it's randomized one-to-one placebo against vaccine. It's randomized two-to-one North America versus Europe. It includes everyone that is supposed to be in need of this vaccine to start with. Therefore, we have everyone in this study five years of age or older. Huge opportunity, very exciting program, and certainly a catalyst program for Valneva in 2025 and 2026.
When we look at the chikungunya vaccine, as I mentioned, we were the first company in the world to bring a chikungunya vaccine to licensure. Chikungunya, again, like Lyme disease, a vector transmitted disease, in this case, mosquito transmitted. It's an outbreak disease with potentially debilitating consequences. It often causes large explosive outbreaks affecting up to 75% of the population. We've seen this across multiple outbreaks in the past. There are also quite significant number of severe cases, including deaths associated with chikungunya disease. Of course, most cases you see reported in tropical, subtropical regions, e.g., South America. We are seeing many countries where chikungunya is at a substantial rise. Therefore, there is substantial quality of life and health economical impact. More recently, one understands better that a very significant number of infected people develop chronic symptoms.
Again, it's something where a prophylactic solution is really creating a huge benefit to mankind, especially when you consider that 75% of the world population lives in area of risk of chikungunya. When we look a little bit at the vaccine proposition, it's a live-attenuated single-shot vaccine that provides long-term protection. I mentioned already the different approvals, the positive CHMP opinion recently to extend the label into adolescence. We hope to get the same label extension across all the regulatory jurisdictions where the product is currently distributed. Of course, when we look at market, what are the markets for a vaccine against chikungunya? Of course, travelers going into chikungunya-endemic areas, the military, but also outbreak preparedness, meaning making sure that the vaccine is available should an outbreak occur. The total estimated market is around $500,000,000.
We have entered into strong partnerships with Instituto Butantan in Brazil, for example, and Serum Institute of India in India to make sure that we provide access to this vaccine in low and medium-income countries. I mentioned already a couple of the forthcoming key milestones. We expect the first approval in LMIC countries in Brazil. We will continue, of course, monitoring the antibody persistence and protection over time. We conduct a phase IV program, which is substantially funded through a partnership with CEPI. It is a highly differentiated vaccine, strong and long persistent immune response and protection after a single dose. I mentioned already the different programs that are ongoing, post-marketing, phase IV, label extensions, as well as to further substantiate the label, especially the long-term protection after a single shot, which could go as far as having a very, very long protection.
We are monitoring antibody persistence and protection levels for up to 10 years right now after a single shot in our program. When we look at Shigella, there is clearly an opportunity here to develop a first-in-class vaccine for a life-threatening disease. I think it's important that this is a very devastating disease, especially for children living in low- and middle-income countries. We got this program into our pipeline through a partnership with LimmaTech. The vaccine candidate includes the most relevant serotypes of shigellosis. The company LimmaTech reported positive phase I/II clinical data in the past, achieved FDA Fast Track designation. As said, we are right now in a phase two challenge study and a pediatric study that is going to be conducted in parallel. Of course, subject to data, we will then proceed into the next development phase.
In terms of market opportunity, there is certainly a very similar profile that you have seen for chikungunya, so travelers, military, but also locally vaccination, specifically in children, given that it's the second leading cause of fatal diarrheal disease with up to estimated 165 million cases and 600,000 deaths annually. Therefore, it got also prioritized by the World Health Organization as a needed vaccine target. When we talk a little bit about our Zika candidate, it is a so-called next-generation optimized vaccine candidate. Valneva worked on an earlier version when the big Zika outbreaks occurred years ago. Now we are working on a novel vaccine that leverages a platform that we developed as part of COVID. And we are targeting here, of course, to address the devastating effects associated with Zika infection, microcephaly, severe brain defects in newborns. I mean, we all remember that Guillain-Barré syndromes in adults.
It is worth noting that right now for this mosquito-transmitted disease, there is nothing available, no vaccines, no treatment availability. Therefore, this indication is on the one hand side, of course, PRV eligible. There are many funding organizations that are currently discussing funding of such a program in the field. We are in the midst of the phase I. We will review towards the latter part of this year the results and then decide on the next development steps, especially given that it is currently unclear how the overall development route to licensure may look like. Therefore, we are also then on the basis of data discussing with the different regulatory authorities around the globe how best, and again, subject to positive data, to develop this vaccine further.
We believe that, like for many of the other things that we are doing in vector-transmitted diseases, that due to global warming, due to the spread of the vectors, chikungunya will become again more and more a significant problem. We have seen that protection protects or infection protects only for a rather short period of time. A vaccine solution is definitely desirable. Therefore, we are excited about this activity. Now let's turn into our commercial business. As I mentioned at the very beginning of the presentation, Valneva is based on a fully integrated model. We do everything from research to sales. I mentioned also that we have been able to grow our commercial business, which is mainly geared towards travel vaccination, substantially. You see here is a history on this slide of product sales over the years. I mentioned already the COVID-19 impact.
I mean, fortunately, we had a solid baseline business even through COVID with the U.S. military. The Department of Defense is the single largest client for our IXIARO, Japanese encephalitis vaccine. Since COVID, we have been able to grow the business again. As mentioned at the beginning of the presentation, we are seeing very strong growth, and we will continue seeing very strong growth in the years to come. The commercial business, despite significant investments that we put into market access and launch activities associated with our chikungunya vaccine, is going to be cash flow positive this year and in the years to come. When we look a little bit into the future and our near and midterm financial outlook, I mentioned already the product sales guidance for 2025. We have a number of additional smaller revenue streams.
That's why you see the total revenues guided towards EUR 180 million-EUR 190 million. We anticipate EUR 90 million-EUR 100 million investments in R&D, partially offset by the grant funding and anticipated R&D tax credits. We are very cash focused and expense cautious. We're going to lower our cash burn in 2025 as compared to 2024 by more than 50%. You see that our guided cash burn is below EUR 30 million for the year 2025, despite a rather high investment level in R&D. Of course, we will continue to focus on cash management, supporting sufficient cash runway to reach the key inflection points. Mainly also here the income that we anticipate on the back of a positive Lyme vaccine approval and first commercialization.
When we look at the more midterm financial outlook, we expect continued travel sales growth for IXIARO and DUKORAL at least for the next two years. Of course, IXCHIQ is going to be the main growth driver in the commercial business. We will see how fast we will be able to ramp up our chik sales and will provide more clarity on the midterm guidance as we get more and more understanding about the uptake of a novel vaccine in a new indication. Our focused expenditure in R&D will be really geared towards a science-driven decision-making process with our key ambition to have a next phase III program ready post-Lyme. Could be Shigella, but could also be any other program. As I mentioned earlier, we expect continuous significant non-dilutive support through grants and other supporting agencies.
Of course, we're going to shift more and more our commercial business back to proprietary vaccines only. During COVID, we entered into a few what we call third-party product sales arrangements. We distributed smaller vaccines for others, leveraging our commercial infrastructure. We are shifting back to focusing more on our proprietary vaccines, which of course is expected to have a significant gross margin improvement. This is further strengthened by investments that we made into more cost-efficient manufacturing, leveraging new facilities that we built during the COVID period and which were supported by certain COVID packages that we got during the pandemic. I mentioned at the beginning already that we could be sustained profitable despite very high levels of R&D on the back of a successful Lyme vaccine introduction. This brings me to the close of this presentation.
I just would like to close up here by reminding where the near and midterm value drivers are. Of course, it's all about Lyme and the Lyme success that we are anticipating. The analyst consensus on this program is around 80% probability of success with first data readout by the end of this year. I mentioned already the strategic importance of this success, namely the financial contributions coming from Lyme and helping the company to transition into profitable waters. We see and expect growing commercial revenues with significant improvement both on top as well as bottom line. We would like to advance our pipeline and by doing so realizing future pipeline value.
All in all, we believe that Valneva is a highly differentiated and very unique, fully integrated company in this space, namely specialty vaccines in areas of high unmet medical need , addressing really the need for vaccines in areas where today prophylactic solutions do not exist. As such, have a unique value proposition that will create returns to our shareholders and value for all stakeholders that can benefit from it. Thank you so much. Any questions? Please.
I think it was a quick strategy question. With something around the 1,000-mercal stage portfolio, kind of what's guiding some of your decisions to build out those early stage packages or R&D?
Yeah. It's a good question. First of all, we believe that we have shown to be able to bring novel vaccines from bench to licensure.
There are very few companies in the world that can say this in our space, in the mid-cap space, I would say. We believe we have the capabilities to bring new vaccines, and we have the ability to continue investing in R&D. Yes, you are right. Especially on the earlier stage part, we are shifting gears a little bit towards, I would call it, higher risk, higher reward programs. Of course, it will all be subject to our financial firepower that we're going to have. We are certainly believing that going forward, we need to take the company to the next level. This means also targeting indications with more significant, also Lyme is already a very significant opportunity, but with more significant opportunities.
Thank you.