Good morning, everyone. My name is Maury Raycroft, and I'm one of the analysts at Jefferies. It's with great pleasure that I'd like to welcome Thomas Lingelbach, the CEO of Valneva. Thanks so much for joining us today, Thomas.
Morning, Maury. Pleasure.
We're going to do a fireside chat format. Maybe to start off, if you want to give a brief intro to Valneva, to those who may be new to the story.
Thanks. Yeah, Valneva is a specialty vaccine company focusing on the development, manufacturing, and commercialization of prophylactic vaccines in areas of high unmet medical need. We have a commercial business in travel vaccination that generates this year, according to our guidance, EUR 160 million-EUR 170 million top line. We have very unique assets across our entire portfolio. Most importantly, of course, the most advanced Lyme vaccine in development in the world, addressing a huge unmet medical need, expected to read out its final pivotal data at the end of next year, which is a big catalyst for the company, but also very recently augmented by a Shigella vaccine that is right now in Phase II . And as I said, across the board, all assets that we have, be it in commercial or be it in development, are very unique, very differentiated, only first or best in class.
Got it. Yeah, it's a great intro. And definitely want to dig into Lyme, but maybe let's start with Ixchiq first, since you've launched this drug recently. Maybe talk about where you're at with the launch and set the stage for the opportunities potential while talking about the different segments of the market.
Yeah, so our chikungunya vaccine, Ixchiq, is the third vaccine that Valneva developed from bench to licensure. It is currently licensed in three major territories: U.S., Europe, and Canada. We had now our first year in the U.S., and we are working to actually penetrate the market right now. This is, of course, quite a challenging endeavor because we are talking about a new disease and a new vaccine in a new disease. So there is a lot of effort that we are undertaking to generate disease awareness, but also penetrate the different channels. There are still a couple of areas that we have not been able to access, especially retail and the retail channel, which requires MMWR release from CDC. And this is important because we have a couple of key population segments that are specifically called out in the ACIP recommendation, including the 65-plus year olds.
Got it. And for the travel vaccine segment, maybe talk a little bit about that. On the recent conference call, you said it's tracking below the anticipated S-curve adoption typical for travel vaccines. How do you get this segment on track? And what metrics and milestones could you share with the public through 2025 to indicate progress?
Yeah. So yeah, as I said, we have really seen sales this year a little bit below our expectations. Having said that, we are very confident in the potential of this chikungunya vaccine because it's highly differentiated. It's the only chikungunya vaccine right now licensed. It has very, very high seroresponse rates and expected to last very, very long, and these key features we will use to really convince prescribers, travelers, military personnel, but also CDC in order to really broaden the recommendation and the uptake. And we are measuring, of course, how we bring the product into the distribution channels. We measure on a monthly basis the stocking, the restocking. We have not yet opened all channels that we have, for example, for IXIARO, but we are on a very good track.
Got it. Okay. And you mentioned the MMWR, which is the Morbidity and Mortality Weekly Report. Maybe talk a little bit more about the importance of that, how that relates to Ixchiq retail sales, and why this matters.
Yeah. So it has to do with the level of insurance coverage, and especially the 65-plus year olds that are covered in the U.S. under Medicare. And so basically, they all rely on access through the retail channel. And therefore, in the retail channels themselves, the big retail chains, they do not build up the product without MMWR. And that's why this is so important. So we are working with CDC to make sure that we get MMWR as quickly as we can. And it's definitely the single largest growth driver that we expect for the United States.
Got it. And there's also going to be another competitor with Bavarian Nordic with a chikungunya vaccine approval set for February 14, 2025. How could this impact Ixchiq in the near term and longer term? And how do you plan to emphasize differentiation between Ixchiq versus Bavarian Nordic's vaccine?
Yeah. First of all, it's great to have two vaccines because it means that you have a share of voice. And when it comes to disease awareness around chikungunya, the more they talk about chikungunya, the better it is. When it comes to differentiation, I mentioned already that we see a couple of key features that clearly differentiate our vaccine. One is the very high seroresponse rate across the entire population that we have tested, especially in the elderly, 65-plus year olds, specifically called out also in the ACIP recommendation. And we have an equally high seroresponse in that population. We reported adolescents' data. And then it's all about persistence, right? I mean, this is a vaccine. Our vaccine is a vaccine that, after one shot, protects for a very long time. We are monitoring antibody persistence for up to 10 years. And we'll report the three-year data very soon.
I think that's something that is probably the single largest differentiation that we see.
Got it. And for ACIP recommendations, you've talked about potential to broaden those. Maybe just talk about that plan and what timelines could look like for this.
Yeah. Good question, Maury. I think there are a couple of things. First of all, we continuously work, of course, with CDC and the Chikungunya working group and all of that. I mentioned that we would like to see the broadening of the age range. We have submitted data in adolescence, which look really great. There is also the point around continuous health economic analysis to support further broadening of the recommendations. There is, as a third element, the usage for endemic area use. There are endemic areas, for example, in the United States, Puerto Rico, Virgin Islands, just to use two examples. It is important that we see also those reflected in CDC's recommendations or ACIP recommendations because this could open the opportunity for stockpiling, which is important for an outbreak disease like chikungunya.
Got it. And at your investor day in October, you mentioned that the Department of Defense for the United States adopted Ixchiq ACIP recommendations into local protocols. So military clinics can start prescribing. What type of utilization are you seeing from the U.S. military so far? And talk about your latest engagement with the DOD as it relates to a potential stockpiling contract?
Yeah. So as you rightly said, DHA adopted the CDC ACIP recommendation, which is step number one. Then there are multiple steps that need to happen in order to get Ixchiq into, let's say, routine vaccination protocol. By way of reminder, for our product IXIARO, it took us three years to get to that point because they need to take many decisions with regards to which vaccines have to be used and when. So right now, they can order, as you said, correctly, and a few doses have already been ordered. But before this becomes really a major opportunity, I think all the respective protocols locally and centrally have to be adopted. And this will take time, and it requires continuous engagement, which we are doing. And this is a key focus that we are currently undergoing in the commercial arena.
Got it. Okay. And you said three years for IXIARO. With that experience, could you potentially accelerate that timeline?
Probably yes.
Okay. So let's move on to Lyme. You mentioned the Phase III study that's ongoing, which is supposed to top line end of next year. Could be a greater than $1 billion market opportunity in the U.S. and the EU. Maybe talk about the study design and expectations for the top line readout by 2025.
We are currently running a very classical placebo-controlled field efficacy study in more than 9,000 people. We have included the entire or the vast majority of the target population. We have everyone above five years of age in the study. The readout is basically the efficacy over two consecutive tick seasons, including a booster. Which means we're going to read out the efficacy after priming with three doses, tick season number one and the first booster, tick season number two. This is basically what we are expecting in terms of the key readout. Of course, then there is a couple of very important further secondary endpoints that are of importance, including, for example, specific efficacy against serotype 1, the most prevalent serotype in the United States. But of course, as usual, safety, tolerability, immunogenicity profiles. These are readouts that will come early 2026.
Then we expect Pfizer to submit in 2026. We hope to get then into approval because it's a fast-tracked program in 2027, including ACIP. And in the ideal world, we would start vaccinating people in the autumn of 2027 to be protected for the tick season or Lyme season 2028.
Got it. Okay. Really helpful. And what more can you say just about how the vaccine rollout could look in the United States and the EU and how the royalty scenarios for Valneva could look as well? And if you can talk more about just the tiering for that from 14% to 22%? I don't know if there's more specifics.
I mean, so first of all, based on the very initial sales in Europe and the U.S. and ACIP recommendation, Valneva will receive more than EUR 140 million in further initial milestone payments. This is the starting point. And then, as you said, tiered royalties between 14% and 22%. We have not disclosed and cannot disclose the different sales thresholds associated with those tiered royalties, but it's substantial. And of course, depending on the ACIP recommendation, we will see a faster or slower uptake of the vaccine. But we expect that the contributions from the Lyme program will drive Valneva into sustained profitability.
Got it. Helpful. And for the milestones, any more specifics you can say about what triggers the milestone payments?
It's going to be very early, and our expectation right now is that those will come in 2027.
Got it. Okay. And then for ACIP, you mentioned that's going to be an important part of this. What are the expectations for what the ACIP recommendation could look like? And maybe talk about age and boosters and what other key variables there are to consider.
Yeah. Good question. So I would say there is a base case. And the base case is certainly that the vaccine will be recommended for special target populations living in Lyme endemic areas. And when I say special, it means associated with certain risk factors. And this is the base, and it's the underlying hypothesis behind the age protections that you mentioned earlier. And for those populations, it would then be included in, let's say, the routine vaccination protocol. That's the base. Yeah. Then there is, of course, an upside case. And the upside case is that it would become a routine vaccination for everyone living in the endemic areas. And endemic areas are very clearly defined globally with more than 10 out of 100,000 cases every year. And that would be a substantial upside.
Given the high, let's say, medical impact that Lyme has and the expected very significantly positive health economic benefit, we see certainly an opportunity for the ACIP recommendation to go towards the upside case. When we talk a little bit about how the vaccine is expected to be used, the point you mentioned earlier about boosters, so our current expectation is that you need a priming and then a booster every year. That we have to see whether this is really going to be the schedule over time. And that's why we are monitoring right now immunological profiles after boosters. We have now, in a subcohort under a Phase II protocol, tested already the second year booster.
We will continue monitoring for further boostering and see whether a booster every year is needed or after a certain time, like we saw it in tick-borne encephalitis years ago, you can reduce the booster necessity over time.
Got it. And for the upside scenario with ACIP, is there a way to potentially influence that beforehand through market research, just information you're getting that?
Yeah. So I would say Pfizer are putting a significant effort behind different epi studies. And they have published in a number of countries already epi studies. They put a lot of emphasis on ensuring that the disease burden is well understood. And on the disease burden, the disease burden understanding is a key prerequisite to essentially provide with good health economic benefits and analysis. And this is the key focus the entire medical team at Pfizer are currently doing. So I would say disease awareness on the one hand side, but also understanding the size of the problem and medical education because the different clinical manifestations and health impairments around Lyme disease are huge and very significant. And this is the key focus. And this is all the pre-work that needs to go into that and is going into that in order to ensure best possible ACIP outcome.
Got it. And can you talk a little bit more about you mentioned the endemic areas earlier? Talk about number of patients in Europe and the United States. And also, how does global warming impact projections just for Lyme going forward?
Yeah. It's a good question. So basically, let's start with the latter part first. We are talking here about a vector-transmitted disease, the vector in this case being the tick. The tick population is at a rise because of global warming, and the pathogen will follow the vector, which means that the more we see in this area, and this is equally true, by the way, for mosquito-transmitted diseases, we will see Lyme cases at a rise. And the numbers are clearly indicating that. We have, over the last surveillance period reported by CDC, we have seen a 70% increase in Lyme cases in the United States. And there is still an expectation that Lyme is very significantly underreported and underdiagnosed. So the experts in the field assume a 10x underreporting right now, roughly, for Lyme disease.
We had, for example, last year in the United States, more than 400,000 reported and confirmed Lyme cases. A very interesting recent study in Germany showed in one of the German Bundesländer, they showed that almost 10% of the population was tested Lyme positive. So means prior exposure to Lyme disease. And we also saw recently through one of the Pfizer epi publications that in the eastern part of Europe, we have a very, very high incidence rate of Lyme disease. So I think this is definitely going to be a very, very growing medical threat. And with all the different and very serious clinical manifestations, we believe that prophylactic vaccination would be very, very beneficial for the society.
Got it. Wanted to move on to a couple other programs in the last couple of minutes. With IXIARO, you've guided to double product revenue by 2026, 2027, including double-digit CAGR for IXIARO for the next three years. What are the key drivers in your projected growth for IXIARO? And what information or insights do you have as it relates to the travel market rebound and military contracts?
For IXIARO, it's definitely driven by travelers. We use the IATA data to basically support our projections. We see that there is a substantial growth in the number of travelers going to Japanese encephalitis endemic areas. We have a certain level of uptake of the vaccine. I would say the growth is primarily driven by the growth in travelers. Of course, we continue to build additional channels for IXIARO as well. These are the key growth drivers.
Got it. And any more specifics you can provide on the IXIARO DOD contracts in 2025, particularly with size and timing for that?
RFP is issued. We have responded to it as usual. It's the same process that we see every year. We expect at this point in time, and we have said this to the market, we expect no substantial growth in the overall military demand. I mean, IXIARO is a mandatory vaccine for forward-deployed troops to Southeast Asia in the military schedule. We have the only licensed vaccine. So I think for us, the business is a very safe bet. Now, it's a certain process that needs to follow. I don't want to speculate about what the impact of the new government is going to be in increasing troop levels or whatever. At this point in time, and our guidance is based on the fact that we continue to see a base business in the U.S. military similar to what we have seen in prior years.
Got it. Okay, and that's actually one of the bigger picture questions I have just with the incoming administration with questions around RFK as well. I don't know if you have perspective on that and how that could play out. I think there's a lot of moving parts and variables.
Yeah. Look, I mean, when you look into the vaccine landscape, some companies have been very outspoken about and speculating about the fact what may or may not happen. I personally would rather prefer not to speculate. So my view is let's wait and see. I mean, I'm in the vaccine industry for more than 30 years. And for me, it's always vaccination has to do with risk-benefit. And for as long as there is a very clear and very positive risk-benefit for vaccination, common sense should prevail. And that's basically my personal view on that.
Makes sense. And with the Shigella, maybe talk about some of the key highlights there. Just recently, your partner, LimmaTech, announced that they vaccinated the first participant in the S4V2 Phase II-B study. Maybe talk about that and just what timelines could look like for completing enrollment for the first step to select a dose and then starting the CHIM in the second step.
Yeah. So our Shigella program is the most advanced program against shigellosis in the world. And there is a dual pathway towards licensure of such a potential vaccine, addressing the two target populations. On the one hand side, adult travelers. On the other hand, children living in endemic areas. And so we run a staggered approach and a risk-mitigated approach with controlled human infection models. And so basically, in the first CHIM study right now, we challenge with the most dominant strain, sonnei. And we will get a readout on, let's say, first indication around potential efficacy against this. But we will also see immunogenicity data so that we can have an idea about how the efficacy against the one challenge based on immunogenicity data translates into others.
Once this data have been read out and positive, we will move into the next CHIM study and from there into Phase III. So always a staggered approach. Of course, it's not designed for a hardcore efficacy readout, but the study has, of course, a sample size. And the sample size is calculated on a minimum of 50% protection against the challenge strain. And that's, let's say, the threshold for proceeding. And then there is an endemic part where we run immunogenicity studies in children and later, most likely, a placebo-controlled field efficacy study in that field.
Got it. And what could timelines look like for that one? And okay, we'll do the last question. Okay. Yeah. We'll wrap up. Maybe provide the highlights for Zika and for investors. What are key events ahead that they should be focused on?
Okay. So let's do it in the last 30 seconds. So Zika, we have currently the only active clinical development program right now in Phase I. We expect readout next year, mid next year. So essentially, when we look at next year and to our investors, we see a very exciting year ahead of us with major, major catalysts working backwards. So at the end of next year, Lyme, Phase III efficacy readout. In the third quarter, most likely Shigella CHIM readout. And over the summer, also the Zika readout. So very important triggers that can provide substantial upside to our shareholders.
Got it. Thank you, Thomas. Thanks for taking the time.
Thank you.