Hi, everyone. My name is Maury Raycroft, and I'm one of the Biotech A nalysts at Jefferies. It's with great pleasure that I'd like to welcome our guest today, Thomas Lingelbach, the CEO of Valneva. Thanks so much for joining us today, Thomas. We're going to do fireside chat format. So maybe to start off, for those who are new to the story, if you can give a one-minute intro to Valneva. Yeah, thank you so much. Thank you for giving us the opportunity to present today and to be here on the chat. Yeah, Valneva is a specialty vaccine company, fully integrated, focusing on prophylactic vaccines, in the areas of high unmet medical need. We have a commercial business, established commercial business in travel vaccines, and we have two late-stage assets, namely, one vaccine against Lyme in phase III, partnered with Pfizer, and, our Chikungunya vaccine, which, just obtained the very first, approval of a Chikungunya vaccine in the world, by U.S. FDA. Very good. Good intro, and much congrats on the approval. Maybe talk a little bit about how the approval label and expectations around the label come up to what you were expecting. Well, so first of all, it's important to say that we feel extremely proud. Because, working on a disease for which, nothing exists, no prophylactic solution, no therapeutic solution, and which represents an area of a growing, unmet medical need is a fantastic thing to do. At the same time, we have been pathfinders, in the regulatory process with FDA because it's the first time that that a vaccine, an outbreak vaccine, got approved through the Accelerated Approval Pathway. So together with FDA, we developed the standards on what it really means to, A, get it approved through an Accelerated Approval Pathway with a surrogate, you know, developed through passive transfer in non-human primates, but also to design a phase IV study or phase IV studies in our case, that show a later real-life effectiveness, which is not easy in a situation where you cannot predict the outbreaks and you cannot predict the incidences. And therefore, this has been a very intense process, and we are very pleased that we have been playing really a pioneering role in this field. Got it. And you mentioned the post-marketing studies, and you talked about this on your conference call yesterday, which would include an observational effectiveness study in Brazil for ages 12 through up, as well as the pragmatic randomized controlled efficacy study in adults in endemic countries. Maybe talk about these studies, and what you aim to achieve with these studies. Well, I mean, first of all, you know, in both studies, we have to show, on the one hand side, effectiveness in real-life settings, but also increase, the safety database, right? Because safety, also, the licensure has been based on more than 3,500 people who had actually received the vaccine. It is important that, you continue monitoring the safety profile of the vaccine, the tolerability profile of the vaccine, and to further educate the risk-benefit, you know, for such a vaccine, which is expected to address a huge, you know, unmet medical need, especially also in LMIC countries, where we have seen, you know, multiple outbreaks, and multiple settings, also in, in, I would say, more established Western countries. You know, we have seen outbreaks in France, Italy, Spain, and with global warming, those vector-transmitted diseases and mosquito-transmitted diseases will be at the rise. Now, in the two phase IV studies that are necessary in future for outbreak diseases in, you know, the accelerated approval pathway, we have to show, first of all, how the vaccine really behaves in a real vaccination setting. So which means we're going to target in a pilot vaccination phase that we achieve a greater than 15% vaccination rate, and also establish the lab network and to see really sero positivity, so prior exposure to the chik virus versus non-prior exposure, what it really does to the effectiveness of the vaccine and the safety and tolerability. That's probably the one part of it, to keep it simple. I mean, we could talk for hours about the details of the studies, but you can look at the webinar presentation that we gave yesterday. The other one is more a controlled setting where you actively control against either a placebo group, so it's called a pragmatic controlled study. So and here we have to select really a region with an outbreak situation. So and we are still in the process of identifying where this will be. Might be also Brazil, but might be also another country. Got it. And maybe talk about just the safety and efficacy portions of these studies and what you need to achieve there, and total number of patients and endpoints measured. And finally, for the cost of this study, how does that work, and also timelines as well? ... So basically, I would say the observational study will target a predefined number of cases. And this has been the basis of the powering of the study. So therefore, it is not predictable at this time what the total N is really going to be. As I said, the important thing is vaccination rate above 15%, and a total case number of greater than 450. This is what we have agreed with the authorities on this protocol. For both studies, immunogenicity, well, effectiveness and safety will be the key objectives. And for the second study, we have estimated around 20. And with regards to costs, I would say, of course, this is a quite extensive phase 4 program. It is the first time that such a phase four program in an outbreak disease is going to be executed. So we hope it will be all executable according to plan, I would say. And we have roughly agreed with FDA that this whole program will, you know, take from around 2025 all the way until 2029. And what we have said is that that the costs will roughly be, or are estimated right now to be roughly in the range of the phase three immunogenicity. More precise, we have not been at this point in time. Makes sense. And, for the time frame, you mentioned that, are there certain time points, additional time points throughout the study where you could have updates? Yeah, of course. I mean, there is the pilot vaccination phase for the 402 study. So, I mean, as we are working on the preparation for those studies, there will certainly be, you know, interim points where we will report on some news flow with regards to the ongoing phase 4. Got it. And are there any specific requirements from FDA as far as that goes on when they want to see updates? Well, of course, in a phase four program, and some of you may look at the approval letter, they have predefined timelines, so they expect certain, I would say, milestones being achieved at certain points in time, and there will definitely be regular updates and interactions with the agency. Got it. And also talk about any other studies you're running, including the immunocompromised study in immunocompromised patients and the timing for when you plan to pursue label expansion in the United States. Yeah. So, we reported actually yesterday in the morning immunogenicity and safety data from the part A of our study in adolescents in Brazil. This data came out as good as it could have come out. And we are using this data for the submission to the European Medicines Agency, but also to ask for label extension in the U.S. in 2024. Then, yes, we plan a study in immunocompromised. We are also planning the pediatric study, so which means for the under 12 years of age. And we will also include in one of the phase three studies, of course. We will also include in one of the phase 3 studies, an earlier time point, to monitor the onset of immunity, because, you know, our phase 3 was designed according to the alignment with the agencies at the time to on a primary endpoint, day 29. We have multiple data points from earlier studies that we have also a rapid onset of immunity, that we're going to achieve the protective thresholds somewhere between day 8 and day 14, but we will include that into one of the phase 3 protocols so that we have also phase 3-powered data on that one. So this will be another, you know, expected readout. Got it. And, maybe talk a little bit about the ACIP meeting and the draft recommendation there. And, just for the vote in February, you mentioned that having the outbreak study designs could be sufficient for the vote. Is there anything else you think they would want to see with those studies as far as progress goes? I, I think we have been entertaining and supporting a very constructive process with ACIP to date. I think at this point in time, we are not expecting that they will need more information than what they have right now. You mentioned draft recommendations. I mean, draft recommendations are draft recommendations, right? So which may or may not be the final ones. Thus far in the draft recommendations, there are no real surprises. And so we are looking forward to the vote in February. Got it. And, for the draft recommendation, vaccination was specifically recommended for adults traveling to areas with a current outbreak, or it may be considered for adults traveling to areas with evidence of CHIKV transmission within the last five years. Mm-hmm. Does this agree with the language you're seeking in a recommendation? Is it clear enough, or what would you define as, like, an ideal definition? Yeah, well, I mean, it's, it's not easy to define the outbreak situation, the, and, and, you know, and it will undergo a permanent change. Because, I mean, as I said, we have seen outbreaks in areas where there have never been outbreaks before. So I mean, the, the definition, where is really an outbreak risk, where has there been an outbreak, will, will be a kind of a moving target going forward. I think the other part that, we looked at quite favorably was that they specifically, mentioned the elderly, and you know that our vaccine performs in an excellent way in elderly. We have, not-- we are the only ones that have not seen any, you know, difference in immunological, serum response in elderly as compared to younger adults. So this is certainly something, a card that we will be able to nicely play. Makes sense. There's been discussion around the market size for Chikungunya. What is the latest on market research? What does it tell you based on different market segments of travel to outbreak regions, government and military contracts, and endemic sales? Yeah. So, Maury, you and I, we had this discussion multiple times. I mean, we are basing our, our, let's say, soft guidance towards a total market size of roughly EUR 500 million by 2032, on the basis of two independent external market studies. I mean, both, you know, see the, let's say, the segment outside of LMIC to be roughly half of that market size. You know, some more, some less. We believe it's too early to further go into guidance on market size because, A, we will undergo many more, regulatory processes. And, you know, every single regulatory authority may take a slightly different stand on, indication, risk, benefit, and as we all know, vaccination recommendations, unfortunately, they are still, handled at a national basis. So we also have to see how the different countries deal with different recommendations, and we believe it would only be prudent to really further fine-tune the commercial opportunity once we see really all those things falling into place. Got it. And, you've talked about not having a government or military contract in place before the ACIP vote in February. Are there good benchmark contracts for what that type of contract could look like? And how do you think about the United States as far as potential initial military contract coming from the US? Well, so first of all, I mean, I have personal experience with two vaccines that got into the military vaccination schedule, one being IXIARO. And you know that for our IXIARO vaccine, the DoD is still the single largest customer. I think typically it takes the DoD a bit of time to update their vaccination recommendations and to translate this into supply contracts and supply agreements. So, we are not seeing this to come, you know, immediately after ACIP, but we clearly see an opportunity and a desire also on the DoD side to get Chikungunya or IXCHIQ in its portfolio. Makes sense. For IXIARO, I think the recent contract you had there was for $32 million. Is that a good reference for what a contract could look like or? Yeah, I think if you look back, with the exception of pre-COVID, we had always single-year contracts. We operate under a single-source supplier contract with the DoD. We have the only FDA-approved vaccine against Japanese encephalitis. And as you know, the number of doses or the value of the contract spans over, always over, a 12-month period. You know, there are... You know, they determine the supply schedule, I would say. The 32 is a minimum. They can go higher than that. It depends on certain factors like throughput patients and others. We see, you know, unless the political environment changes, we see this pretty stable in terms of consumption, and we see this probably to represent quite a good analog of what we may expect going forward. Got it. For getting the approval, you qualify for PRV. Talk about the value of that and how you see the market for selling that PRV. Well, I mean, we have publicly stated that... So first of all, we got the PRV, hallelujah, right? So, and so, we also said publicly that we got to monetize this PRV as quickly as we can. We have engaged a bank that you probably know very well, Maury. And, so basically, we have, and we are in the process of really launching a potential sales process. I believe that there is a market, and you know that, historically, over the past, you know, couple of years, at least the last three years, the, let's say, the market price has been centered around ±$100 million.... for the PRV, and this is also what we included in our, in our financial guidance for the year, and we have no reason to believe that we may not achieve that at this point in time. Got it. Makes sense. And for people tweaking their models with thinking about the launch, you said, what do you expect prior to the ACIP vote as far as revenues from CHIKV? Oh, this is a very good question. Very difficult to answer. I mean, we have agreed as part of the approval with FDA, the lot release protocol. We have the launch lot ready, waiting now, you know, final labeling and packaging, and as soon as we have that, we're gonna move the product into the U.S. And then we have to see whether there will be pre-ACIP, you know, orders. And then typically, you know, for other vaccines, we have seen that there is some, you know, what we call channel sales, you know, going in, but it is very difficult to say at this point in time. We are on working day number 3 post-approval, so, it's probably not prudent to give any guidance here. Got it. And, maybe talk about the sales force and potential overlap with your current sales force. So number one is, you know, we are one of the very few companies that has an established, commercial infrastructure in travel. It is a commercial infrastructure that targets specific segments. We have it in key markets, basically in all key Western travel markets, except Germany, probably, where we work with our long-term partner, Bavarian, together. And basically, right now, there is, of course, a huge synergy. There's a bundling effect in, you know, in the travelers segment. At the same time, you've seen in our last financial report that we are investing quite significantly in sales and marketing, which is a combination of, you know, increasing the number of staff on the ground, but also, you know, brand managers, MSLs, because it will all be about medical education, supporting all the processes around, vaccination recommendations and the like. Makes sense. And, let's shift gears to Lyme Disease. You're currently in a phase III at Pfizer for this program. Maybe talk a little bit about the study and currently where the study's at. Yeah, of course. I mean, we are extremely excited about the Lyme vaccine development. We are also extremely excited about the Lyme partnership with Pfizer. I think. I mean, undoubtedly, you know, Lyme represents one of the very, very big untapped, you know, I would say, vaccine-preventable diseases in the Northern Hemisphere. And the phase III in around 9,000 people is currently ongoing. We do a placebo-controlled field efficacy study, randomized 1 to 1 against placebo, randomized 1 to 2 in between Europe and U.S. It includes the entire initial target population, meaning everyone above 5 years of age. We want to make sure that we have fully powered efficacy data for the main or for the key future segment. I mean, the first cohort has been, you know, basically completed its first tick season. So the first cohort will get a booster, you know, for the next tick season. Second cohort is enrolling, and we expect the enrollment to be completed on time, so that those people are really, you know, fully immunized well ahead of the next tick season and in time with the peak profile of the tick season. So no issues on enrollment, no difficulty finding people to be part of the Lyme studies, and so far, so good, I would say. I mean, we have a lot of flanking, continuous data points, minor ones, on coming from the follow-up from the different phase II studies, as you know, including, you know, persistence of antibodies over time. The real readout on Lyme will be at the end of the tick season 2025, where we will read out both the efficacy number post-priming, as well as the efficacy number post-priming plus first booster. Got it. And is it possible that you might do a Cohort 1 early readout from that? No, we have. I think we discussed this opportunity or possibility with Pfizer at length, and we concluded that the incremental sample size would not justify, or the incremental sample size needed would not justify the earlier readout. Therefore, we decided to go for the final readout at the end of the second tick season or third tick season. Makes sense. And, maybe briefly just talk about the process that you'd have to go to, for the Lyme disease or for the Lyme vaccine program. Is it similar to, CHIKV and ACIP, or is it something different? No, I mean, first of all, it is a different regulatory process because we are talking here about a standard licensure process. Also, it's fast-tracked, which is very important. But it's based on an efficacy study, but we expect, of course, also an ACIP process. And so the and this will all be prepared well in advance. Similar, you know, market access activities, you know, market preparation activities, which will all be done by Pfizer. Got it. And we didn't talk about the rest of your pipeline, which you started to talk about more recently. Maybe provide a highlight for the rest of your early-stage pipeline. Yeah. So, so basically, I, I mean, we have reinitiated our Zika vaccine development. Why? Because, A, it's another outbreak disease in an area of very significant unmet medical need. And we were one of only two companies that worked on a program pre-COVID, where we showed good data. We further optimized the formulation, and we'll go into another clinical trial early next year. You know that especially for Zika, WHO recommended to limit vaccine development to, you know, non-reactogenic technologies, I would say, or technologies that are based on a well-known established tolerability profile. Especially, you know, inactivated whole virus approaches have been called out, which is why we believe we could really play a pioneering role in that as well. By the way, it's also a PRV-eligible disease. And it will also follow Accelerated Approval Pathway, and with all of our experiences, we believe it's a nice fit. It's also gonna be a nice industrial and commercial fit going forward. Also, the commercial, you know, kind of opportunity right now is under evaluation, not only by us, but by many others, because it's really unpredictable. And then on top of that, I mean, we have said publicly, I mean, we are a mid-sized company. We have, in our history, brought now three vaccines from bench to licensure, which I don't think is something many smaller companies can say. But we have a kind of an earliest clinical stage pipeline gap, which is a result of the fact that during COVID, we worked on a COVID vaccine, which became the first one to receive an ordinary license in Europe, but we came too late, so decided to stop the endeavor on COVID. But it resulted in a situation that outside of tick and Lyme, we had to put the entire R&D team on COVID. So therefore, we have quite exciting early-stage work right now. We have just completed HMPV for preclinical proof of concept, and we are looking to potentially partner this asset with someone who sees value in an RSV HMPV combo. We are one of the companies working on EBV, which is really a very, very big but also complex development, and we are working towards antigen identification and prioritization of certain antigens. Yes, we will try to augment our pipeline strategically. We have a couple of processes ongoing right now to potentially partner and/or in-license earlier-stage clinical assets. But I think it's fair to say that, you know, amongst all these mid-sized vaccine companies, we are the only ones that are absolutely technology agnostic. We have experience with all different kind of vaccine technologies. All of our programs are based on different technologies, and so we need to fulfill our investment criteria, meaning first, only, or best-in-class. So if the product will not have the possibility to meet one of those three criteria, we're not gonna do it. And that's why we are currently going through the evaluation, but it's one of our declared strategic objectives for 2024. And I would say we are well prepared for it. Very good. Thomas, congrats again, and thanks for joining us today. Thank you so much.