Thank you, Nadia. Hello, and thank you for joining us. We're excited to discuss the recent FDA approval of IXCHIQ, the world's first chikungunya vaccine and the third vaccine the company has advanced from early development to commercialization. It's my pleasure to welcome you today. Please note that you can find our press release from Friday and the analyst presentation published earlier today, available within the investor section of our website. I'm joined today by Valneva's CEO, Thomas Lingelbach, and Chief Medical Officer, Juan Carlos Jaramillo, who will provide an overview of chikungunya and IXCHIQ, the market outlook, and the ongoing and planned clinical development activities. There will be an analyst Q&A session at the conclusion of the prepared remarks.
Before we begin, I'd like to remind listeners 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. Please note that today's presentation includes information provided as of today, November 13th, 2023 , and Valneva undertakes no obligation to revise or update forward-looking statements except as required by applicable securities laws. With that, it's my pleasure to welcome Thomas to begin today's presentation.
Thank you so much, Josh. Yeah, so Valneva is really excited about this first approval of the world's first chikungunya vaccine, IXCHIQ. As a leading specialty vaccine company, you know that we aim to deliver vaccines in areas of unmet medical needs, supporting our vision to contribute to a world in which no one dies or suffers from a preventable disease. As such, this important milestone marks an important step forward in the prevention of chikungunya. I would like to personally express a huge thank you to everyone who helped make this possible. I would also like to recognize CEPI and Instituto Butantan for their collaboration in potentially bringing this product to low- and middle-income countries. With that, it's a pleasure to hand over to my colleague, Juan Carlos, to start with the presentation.
Thank you, Thomas, and good morning. Good afternoon, everyone. To begin, chikungunya virus is a serious and debilitating mosquito-borne viral infection that poses a significant unmet medical need globally. It's currently regarded as one of the most likely viral infections to emerge in new geographic areas, making this a major public health threat. The disease is transmitted by the Aedes aegypti and Aedes albopictus mosquitoes, which often cause large outbreaks affecting one third to three-quarters of the population in the local setting. We have witnessed and documented that chikungunya outbreaks are explosive and rapidly moving, but not predictable, usually overwhelming the local healthcare systems. Outbreaks have occurred in Asia, Africa, across Latin America, more recently in Europe, specifically Italy, with the potential to spread further in regions across the European market and also the United States.
The most recent large outbreak was captured in Paraguay early this year, with over 110,000 cases reported in the first three months, after which PAHO issued an epidemiologic alert for the Americas. Next slide, please. Today, it is estimated that more than 75% of the world's population live in areas at risk for CHIKV transmission. Transmission has been reported in more than 110 countries globally, and the areas of greatest risk for travelers are thought to be the Americas, parts of Africa and Asia. Travelers that are infected and returning home from these areas can, in addition, trigger local outbreaks. Most concerning is that the modeling now shows that the problem may only get worse due to global warming and climate change.
As temperatures continue to rise, we are likely to see vector habitats expand, which pose an immediate risk of outbreaks in warmer areas of the United States and Europe. Next slide, please. There is a high disease burden that comes with a health economic impact. The disease causes high morbidity, which is characterized by sudden onsets of high fever and joint pain. There are well-established publications that 43% of the patients that get chikungunya virus develop chronic disease with debilitating joint pain that may last for months to years and may never fully recover. Next slide, please. The economic burden caused by chikungunya virus disease is significant and is driven by a combination of various factors, mainly hospitalizations and the related costs linked to the loss of productivity. The cost of local outbreaks usually runs into $10s of millions.
Seen here on the slide, the large outbreak in the U.S. Virgin Islands in 2014 and 2015 had cost them approximately 1% of their GDP. Next slide, please. As seen on this slide, the disease has a huge impact on health-related quality of life, which is caused by pain. There are physical handicaps in daily life, with many downstream effects on physical and mental well-being. The quality of life of these patients with chronic, long-lasting sequelae can be compared with those living with moderate rheumatoid arthritis. Now, Thomas, I hand it back to you.
Thank you. Page nine of the presentation shows the development path to date for, as Josh mentioned, Valneva's third vaccine that we've brought all the way from early R&D to approval. Since we began to in-license and pre-clinically develop the product based on our collaboration with Peter Liljeström and the Karolinska Institute, we have gone through major steps in the development. We had shown initially efficacy and 12-month persistence in non-human primates, followed by a phase I that was unique in its nature because it included an intrinsic virus challenge. It showed already a 100% seroresponse rate, and a safety profile that supported going straight into phase III. At that point, we also started our collaboration with CEPI.
In a non-human primate study, we showed protection and passive transfer models and established an immunological surrogate and phase III endpoint needed for the so-called accelerated approval pathway. We went through phase III, and basically, the phase III data were excellent, and I come to that in more detail. We started the rolling submission with the FDA in 2022, and as we all celebrate today, got the initial U.S. approval on November 9th, by way of accelerated approval pathway for adults aged 18 and above. We also received, as you already heard, our priority review voucher, which we expect to monetize to fund further, R&D investment for Valneva. We are now looking forward to ACIP recommendations expected in February 2024. What are the key clinical highlights to date for this vaccine?
With the trade name IXCHIQ and the development name VLA1553, it is a live attenuated vaccine that demonstrates rapid and long-lasting immunity with a single shot. The core immunogenicity data clearly show a 99% seroresponse rate after a single vaccination, and the immunogenicity profile is maintained over time. We showed close to a 100% after 12 months, and a 24-month time point is shortly coming up. Older adults achieved a similar seroresponse in neutralizing antibody titers as younger adults, and the 100% seroresponse after 14 days is already sustained up to month 12.
In the adolescent trial that we reported, the trial met primary endpoint, highly immunogenic, also in baseline negative individuals, and as we reported this morning, also very importantly, the safety profile in a positive way, even in people who had prior exposure to chikungunya. On safety, the vaccine was generally well tolerated amongst the more than 3,500 adolescents and more than 750 adults and 750 adolescents evaluated for safety to date. The pooled safety data showed that around 50% of study participants had solicited systemic adverse events, most commonly headache, fatigue, and myalgia. The majority of solicited adverse events, however, were mild or moderate, and 2% of study participants reported severe solicited adverse events, most commonly fever.
And the adolescent trial, as I mentioned already, suggests a favorable safety profile regardless of previous chik infection. When we turn to page 11 of the presentation, you see the really compelling, overall immunological response across different studies. On the left-hand side, you see that we see generally a close to 100% seror esponse rate, and on the right-hand side, you see what I mentioned earlier, namely, that they have absolutely comparable titers in younger and older adults. Page 12 of the presentation clearly shows also the onset of immunity. Here, data from different trials, because in the phase III pivotal study, the primary endpoint was day 29. But as you can see from the different datasets, somewhere in between day eight and day 15, we surpassed the sero response threshold that is likely to predict efficacy.
We will evaluate this also in phase III powered setting in one of our forthcoming studies. Now, when we look at the phase IV requirements that are needed under the accelerated licensure pathway, I would like to point out the phase IV into two key post-marketing effectiveness studies. One called VLA1553-402, the other one, VLA1553-404. 402 will be an observational effectiveness study in population greater than 12 years of age in the endemic areas of Brazil. It is intended to estimate the efficacy of IXCHIQ in the prevention of symptomatic laboratory-confirmed chikungunya virus infection cases after a single vaccination. The test- negative control study, validated with RT-PCR case confirmation, for which we need around 450 cases and around 890 controls.
The municipality selection will be based on CHIKV risks and test infrastructure. The whole study will be started with a pilot vaccination period to ensure that we are getting to the estimated greater than 15% vaccination coverage, and include a safety evaluation, meaning incidence of medically attended AEs in about 5,000 people. It will also include a survey, sero survey, meaning pre-exposure assessment. The timelines that we have committed with FDA are in between 2025 and 2028, including the pilot phase. For study 404, study 404 was basically introduced since there's a statutory requirement for well-controlled clinical investigation as part of the accelerated approval pathway, and it is introduced to address potential biases associated with the pure observational design.
The objective for this pragmatic, randomized, controlled effectiveness and safety study in adults in an endemic country, for which we estimate a sample size of around 20,000, is to assess efficacy of IXCHIQ in the prevention of symptomatic laboratory-confirmed chikungunya cases after a single vaccination compared to control participants during the same trial period. There will be a one-to-one randomization in between IXCHIQ and placebo or an active control. Safety evaluation will include around or more than 10,000 individuals for severe chikungunya-like adverse reactions and prolonged arthralgia. Again, study period here a bit longer, from 2025 to 2029. Page 14 shows a slide that we showed last week at the analyst report, basically outlining that external studies clearly evaluated that the chikungunya market is estimated to exceed $500 million per year by 2032.
We have basically a number of different segments. One, on the left-hand side, you see the segments that are targeted directly by Valneva, namely travelers from non-endemic regions to areas with high risk of or risk of chikungunya, military from endemic regions, but also outbreak preparedness in response to a potential risk for a domestic outbreak. Some people call it also stockpiling or outbreak preparedness programs. And then, most importantly, also here, the segments that we are targeting by our partnerships through CEPI and Instituto Butantan, primarily the LMIC markets. And this is an important part for the future commercial profile of this vaccine. We estimated previously that the left-hand side of this entire market segment will present roughly half of the total market potential.
Turning to page 15, IXCHIQ fits perfectly within our existing commercial infrastructure. We have a high caliber team with significant experience in the vaccine space, both from a commercial perspective, but also from an industrial perspective. So we expect really to commercialize this vaccine ourselves for all countries except the LMICs. Through our existing commercial infrastructure in most of the key markets, which we have extended through well-established distribution partners. We have an integrated sales, marketing, medical, and market access, government affairs capability, focused on increasing awareness and unlocking the brand's potential. We will leverage data-driven insights and digital tools to enhance commercial capabilities and make this vaccine a success over time. Juan Carlos?
Thank you, Thomas. So going on slide 16, I will now briefly describe the key features of IXCHIQ. It's the world's first licensed vaccine, and it's indicated for the prevention of disease caused by chikungunya virus in individuals 18 years of age and older who are at an increased risk of exposure to CHIKV. We expect to benefit by being the first to market with a potential best-in-class vaccine. We also believe we have differentiated and competitive product, characterized by strong and durable immunological response from a single injection. We have seen that no overall differences in immunogenicity between the younger and older adults, for example, 65 and above, and generally well tolerated among the greater than 3,600 adults and 754 adolescents evaluated for safety. Thomas, over to you.
Thank you. Yeah, last slide on this presentation, page 17. We mentioned at the very beginning, this is the first approval of the world's first chikungunya vaccine, but we hope to see more approvals coming in the future. This map outlines how we are going to prepare for global market launches. On the left-hand side, the U.S. Here, I think it is important that with the adolescent study data that we reported earlier today, we expect next year to support a label expansion for this vaccine, allowing the vaccine to get approval also for everyone above 12 years of age. We have filed the NDS with Health Canada and expect the review completion mid-2024.
We have Europe, where we filed the marketing application with EMA in October of 2023. We got accelerated assessment by CHMP granted. We expect further additional countries with established travelers or endemic markets to follow after U.S., Canada, Europe and U.K. With regards to LMIC, and our partnership with Instituto Butantan, we would like to file IXCHIQ early next year with potential licensure in 2025, and then complete the tech transfer, and get licensure for a locally produced product called VLA1555, potentially also in 2025. Other LATAM or LMIC countries are expected to follow. We will go through a prioritization in 2024, and expect already first submissions in 2024, which could also lead to WHO prequalification.
With all of that, we expect this exciting new vaccine, and first vaccine under Accelerated Approval Pathway, in an outbreak indication, really to follow a global reach, over the years to come and addressing a very high unmet medical need as outlined by my colleague. With that, I would like to hand back to the operator to take your questions.
Thank you. Dear participants, as a reminder, if you wish to ask a question, please press star one one on your telephone keypad and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by. We will compile the Q&A roster. This will take a few moments. Now we're going to take our first question, and it comes from the line of Evan Wang from Guggenheim Securities. Your line is open. Please ask your question.
Oh, great. Hey, guys. Congrats on the approval. Great to see you guys cross the finish line. Would love to hear, you know, some of the pre-commercial prep you're going, you have going on, and how we can think about, you know, start thinking about the launch now, you know, maybe in the context of the ACIP meeting, how early are you prepared to begin marketing, this product? Any kind of considerations you can provide in terms of, you know, available doses? And two, you know, great to see, you know, some of the consistency of adolescent data. I think, you know, you saw, you know, we saw the approval letter, some of, you know, some of the required studies for, you know, pediatrics and at pregnant women population.
So, I guess, how are you thinking about, you know, some of the filings? I guess you mentioned in adolescents, but beyond, and do those required studies accelerate some of the timelines there? Thanks.
Okay. So let me get started on some a couple of points. I will, first of all, address all the other, let's say, studies to come, and before I let also Juan Carlos talk a little bit about the way we are currently preparing for commercialization in the United States, but also the ACIP process. So yes, you rightly mentioned that, we are planning a quite significant number of further studies in the field of chikungunya. Besides, the phase IV studies that were clearly mentioned as the two key slides on the key two studies that I mentioned on the slide. Sorry. There are, of course, pediatric. There's a pediatric study that we are planning to start next year.
And there is also a study in immunocompromised that will start very soon. So which means 2024 would be a year where we expect to really kick off a couple of main studies going forward. I think with regards to supply, we have already agreed with the FDA on the last release protocol. We have launched material ready that will go through as respective release procedures, final labeling and packaging, and should be available very early on in 2024 in the United States. Juan Carlos, a couple of words to market preparation in the ACIP.
Yes. Thank you. So we, we have initiated about 24 months ago, making sure that we have the right, teams in place, hiring MSLs in, in some of the regions, and also looking at pre-launch activities. So we've done various analysis of the gaps. First, making sure that we understand the importance of educating and bringing chikungunya disease awareness, not only to the prescribing physicians, but also to the general public. I think for us, is one of the most important parts is looking at now with the approval, especially with a final label, is working with ACIP, as we are being asked to provide information and data to them.
As you've probably seen, there will be an ACIP recommendation in February of next year, and we're working closely with the ACIP working group lead in order to make sure that the timelines are kept from our end. With regards to the launch, teams in the U.S. are well prepared, and we're looking forward to having this product on the market as soon as possible and benefit it to the people that need it the most.
Great! Congrats again.
Thank you. Now we're going to take our next question. Just give us a moment. And the next question comes to line of James Stamos from Jefferies. So line is open, please ask your question.
Hi, this is James on for Maury. Congrats on the approval. Thanks for taking our questions. So for confirmatory efficacy, you've talked about the phase IV outbreak study. How is that going to be run logistically, including how many patients and which countries? And then you've also mentioned a study in immunocompromised subjects, presumably that will be used to expand the label, but does that also satisfy the safety requirement?
Good question. So couple of different things. So safety not on the immunocompromised, of course, this will support further safety database, but will not be sufficient overall. So the two studies that I mentioned, which are shown on page 13 of the presentation, the one study, named 402, which is really the observational effectiveness study, in everyone above 12 years of age, will be done in Brazil. And as I tried to explain, when we talked about this slide, it will be preceded by a pilot vaccination, where in selected municipalities, based on CHIKV risk, and we need to see that we achieve there a greater 15% vaccination coverage before the main part of the study, you know, basically starts.
Since this is a test- negative case control study, by the end of the day, the number of cases count in order to achieve the necessary power. So it's not, we cannot say how many people we really need at this point in time, because as I said, this will all, you know, be developed as we are going through the pilot phase and as we are then conducting, the observational, you know, effectiveness study. The study 404, however, is a pragmatic randomized controlled study. Here we know that we will roughly have a sample size of give or take 20,000, in an endemic country. We have not chosen this country yet.
We're gonna work on that, you know, over the course of next year, for a study start in 2025.
Okay. Thanks for that. Could you potentially get a U.S. military contract done prior to the ACIP vote in February? And have you been having preliminary talks there? What about talks around government stockpiling for outbreaks?
All discussions around, be it military, be it potential stockpiling, those discussions, of course, have been initiated, and will be further intensified now that we got the approval. But in order to manage expectations, we do not expect anything right now prior to ACIP. Based on our own experience, from IXIARO, but also from other vaccines I've personally worked on, it would take a bit longer for the U.S. military to come up with their respective vaccination recommendations and potential procurement plans.
Thanks for that. And final question. So for commercial launch, what do you expect prior to the ACIP vote in February? And how do we think about the launch in general? Is IXIARO a good precedent? Finally, how are you thinking about pricing?
JC?
Yes. It's a very good question, and thank you. I'll start off first with the pricing. I think that we, during the ACIP working group, I believe held in October of this year, they were discussing around how the health economic model and also the budget impact models were being looked at. Currently, we are anticipating that our price will be similar to other travelers vaccines in the U.S. This is also something that we are finalizing at the current moment with that.
Regarding, yes, we've taken the uptakes and also looked at the marketplace around travelers, and we are mimicking in certain launch activities where we are targeting specific travel agencies and travel departments in the U.S., and this is how we expect to enter the market, hopefully soon.
Okay, great. Thank you for taking my question. I'll hop back in the queue.
Thank you. Now we're going to take our next question. The next question comes to line of Samir Devani from Rx Securities. Your line is open. Please ask your question.
Yeah. Hi. Hi, everyone. Let me add my congrats on another great achievement. I guess I got two questions. Just in terms of the phase IV studies, you're talking about commencing those from 2025. So I'm just wondering, is that due to you waiting for formal licensure in Brazil? I guess that's the first question. And then, just maybe in terms of first shipments, when should we expect you to be making first shipments to the travel centers? Thanks.
Yeah, so to your first question, Samir, yes, of course, that's the reason. So we need IXCHIQ approved in Brazil. And to your second part, as I said, I mean, we have launch material ready. We're going through the launch procedure, launch release procedure right now, and then, you know, labeling, packaging, and then we will check. So we expect, you know, early next year, arrival of the product in the United States. Very early.
Great. And maybe just one further one. How much launch stock or how many doses in the launch stock do you currently have?
Samir, I need to follow it up. I don't want to give you a wrong answer, but I would say definitely more than sufficient. We can follow up, because I don't want to give a wrong number here.
Okay, that's great. Thanks very much.
Thank you. Dear participants, as a reminder, if you wish to ask a question, please press star one one on your telephone keypad. Now we're going to take our next question. The next question comes to the line of Max Herrmann from Stifel. Your line is open. Please ask your question.
Great. Thanks very much for taking my questions, and congratulations on a great approval. So two questions. Firstly, just in terms of your relationship with the Instituto Butantan and the potential for use in endemic regions, I wondered what the kind of royalty or what the agreement are, and what's the commercial relevance for Valneva? Then secondly, just to clarify on the observational study, I'm trying to get my head around it a little bit. I thought they said that that was an efficacy study, but seems more of a safety evaluation. Is that what—What is the primary objective of the observational study? Thank you.
So the observational study is a combination of both. That's very clear. With regards to Butantan, so basically, the Butantan agreement under the CEPI umbrella ensures, you know, access for LMIC countries, and through Butantan, meaning through local manufacturing, which is what, why we are also local secondary manufacturing, I should say. Which is why we are calling it VLA1555 in all the presentations, which has nothing to do with the initial licensure of IXCHIQ in Brazil. So these are two different things. Yeah, so Butantan is expected to produce locally for LMIC countries.
Now, whether this will really cover all LMIC countries or whether we will, you know, manage some of the LMICs direct, this is still something that we will further evaluate, but for the time being, Butantan is expected to cover all LMICs through supply at Butantan. Valneva will provide drug substance at a predefined tech transfer price, and Valneva will also receive royalties on sales. That's how it works, Max.
Right. Just to follow up on the observational study in Brazil, I take it that's gonna have to be quite a long-term study. So you, you're saying you're gonna look at various municipalities that maybe have a high risk of chikungunya, then vaccinate over 15% of the population in those regions, and then look at the outcome data, both in terms of safety, adverse event reporting, but also prevention, potentially.
Yeah. So we start, of course, with the safety evaluation in the pilot vaccination period, and then will be followed through the observational effectiveness, you know, part. And as you have seen, I mean, 2025, 2028, this is already a long period. So, and, please also keep in mind that we are breaking new grounds here, right? I mean, you know, this is the first time that we see all of those, those kind of studies in an outbreak disease. I mean, all experts right now, at FDA, and other institutions believe that this is feasible, but yet to be verified, Max.
Right. No, appreciate it. Okay, thank you.
Thank you. Dear participants, as a quick reminder, if you wish to ask a question, please press star one one on your telephone keypad. There are no further questions. I would now like to hand the conference over to the management team for any closing remarks.
Thank you so much for your time today. Thanks a lot for all your nice words of appreciation that we will, of course, share with all colleagues at Valneva who make it happen. Thank you so much, and have a good rest of the day. Bye-bye.