Well, thanks for joining us today, everybody, at the Citizens JMP Life Sciences conference in 2024. Pleased to have DBV Technologies joining us for a fireside chat. My name is Jon Wolleben, and I've been covering this story since, I think, 2016 or 2017, which predates you two a little bit. But we have CEO DBV. By quite a bit, actually. CMO Pharis Mohideen here to help talk us through the story. Good morning, all. And everything that's going on. So thanks again for freeing up the time, guys. Oh, please. Thanks for having us. Well, I think maybe a good place I'd like to start is just very high level, what you guys are focused on for those unfamiliar with the story, and then we can dig into more of the details. But high level, strategy and focus for you guys at DBV. Sure. Yeah. We're a pediatric immunology company focusing on the fact that the human skin is actually a pretty powerful immune organ. We're using patch technology worn on the scapula of children to desensitize them against allergens. Our lead product is for peanut. The platform is called Viaskin. So the lead product is called Viaskin Peanut. That's our area of focus, pursuing 2 BLAs in parallel, 1 in toddlers 1-3, and 1 in children 4-7. We hear about peanut allergy all the time. In the news, usually under very bad circumstances, deaths pretty much every year. If you have young children, obviously you see peanuts in most schools, airplanes, etc. Can you put some numbers around what we know about prevalence today? Then you guys are looking at two different age groups. Can you tell us a little bit about where you're looking to apply your technology and then what we know about the prevalence and the unmet need, why we need a therapeutic? The highest unmet need is in children 1-5, because that's typically the age of diagnosis, which for all food allergies, which makes sense, this is at the age where you want your kids to explore and try new foods. And obviously you might uncover the allergy to one of them. So 1-5 is the age of diagnosis. We also know that as a rule, pediatric, the younger patients are best responders to all forms of immunotherapy, certainly ours also. Our data anchors that quite strongly. So indication 1-3 and 4-7 is for historical reasons, which you can come to if you wish. And that is our area of focus. It is estimated there's about 670,000 kids in the U.S. through the age of 1 and 7 that have a confirmed diagnosis of peanut allergy, making the annual incidence to be about 72,000 kids born every year with the condition. And then is there heterogeneity in peanut allergy, or is it I've got an 18-month-old. If we found out he had peanut allergy, it'd be like, all right, we're not having any risk here. We'd want to get treatment. Any sense about people that kind of understand they've had a reaction and they don't worry about it, or do all of those parents and families want to go seek a treatment? Yeah, sure. There's a whole spectrum of allergic reactions. You can have relatively mild, and then you can have life-threatening anaphylactic reactions. The trigger or the amount of peanut protein can vary tremendously. The thing that makes it difficult is that what you tolerate on a given day can change based on something as simple as how much sleep you had the night before. So it's a relatively complicated disease with a lot of moving parts. So really, it's not a one-size-fits-all for each individual subject. Yeah, I'll add to that. Your previous reaction is not indicative of the severity of your next one, which is why it makes it so haunting to parents. Scary, yeah. There's a seminal study out years ago now showing that early introduction of peanut protein can reduce the incidence of peanut allergy later on. Wondering if we're seeing that translate, what does the trajectory of the prevalence look now? Because even, like I mentioned, with our son, we had the peanut puffs, so we gave it to him. We anxiously waited six hours, and now once a week we give him more peanut puffs just to have that early introduction. But are we seeing that translate in numbers quite yet? It's not translating into numbers. The incidence is pretty much the same. If anything, it's still going up as a percentage of population. Two studies, one in Sweden and one in Australia, looking at whether post-introduction of these feeding guidelines, the incidence dropped showed that there's a reduction that was quite small, in part because there's some confusion around the protocol is which amount given when. And the compliance by parents is also very difficult given the fact that young children are young children. So there's many other things you have to manage. So in real life, those strategies have not shown to be successful in reducing the incidence of peanut allergies. Yeah, we all know we should exercise and eat vegetables, and we're correct, yeah. Correct. And And only have three beers. Yeah. And one other kind of market dynamic I want to ask you about is we had a recent approval for Xolair for food allergy. Can you talk a little bit about that product vis-à-vis Viaskin Peanut and then how that might change the opportunity, if at all? I'll start with your last question. It's not going to change the opportunity for us at all. That being said, Xolair's approval is significant for the members of the food allergy community and the peanut allergy community. But the patient population is very different. We see it being used in older children and adolescents, particularly because adolescents perceive to be at higher risk. They may not pay attention to what they're eating. That it would be used also for people going to be for a while in a higher risk situation, for example, traveling to part of the world where the labels might not be quite as reliable, will be camping or trekking, so away from emergency rooms. We see it being used there. And when we say we, in dialogue with the KOL community, that's what we hear. And then some patients as a bridge to OIT. But as you know, it blocks immune response. It's not a form of immunomodulation that can reeducate the immune system. In the younger patients, which is the ones that we are targeting, we're hearing that there's a preference for something that may be transformative to the disease, which our product indicates maybe. And in that regard, we see Viaskin Peanut addressing a very different population and need within that population than Xolair does. I'm not sure we touched on this. Can you talk about the use case for Viaskin Peanut in the real world? Yeah. The indication will be for the prevention of allergic reactions, including anaphylaxis, as a result of accidental peanut consumption. So that's going to be a protection against what is actually scaring parents. So both the medical risk of anaphylaxis and, I would argue, just as importantly, if not more importantly, this anxiety that essentially becomes part of family life is today the day I'm going to get a phone call from school or from the basketball coach that something terrible has happened to my child. So parents are looking for also the peace of mind that comes with adding that element of incremental protection, above being vigilant to labels and talking to the waiter and talking to the babysitter, as well as carrying an EpiPen. That's going to be part of the background anyways. But a treatment such as Viaskin Peanut, simple gesture every day to provide that layer of protection that also translates into reduction of family anxiety, is really what we're addressing. Does that answer your question, in part? No, in part. No? OK. Logistics of Xolair versus oral immunotherapy versus Viaskin Peanut and how it's actually administered. Oh, sorry. Xolair is an injection given every 2-4 weeks. That blocks IgE response. While our product looks at a Treg stimulation to the lymphatic system as to reeducate the immune system to not recognize peanut protein as being dangerous. So the MOAs are radically different. And obviously, the implied we're not making claims, but the implied long-term benefit of one versus the other are very different. If you stop using Xolair, you don't have a protective effect anymore. There are reasons to believe that with immunotherapy, you can achieve what would be a more sustained unresponsiveness. Again, to be clear, we have data that indicates it's a possibility. We'll have to do the longer-term studies. But at the mode of action level, these are two radically different ways to approach a therapy. OK. Does that answer your question? I was looking for a once-a-day patch. Do you want to change seats with me? What I might add to that for omalizumab is a couple of things. So with blocking the immune system at such a young age, there's some reluctance in terms of is there any consequence long-term when the immune system is still developing? That's one thing we've heard from our investigators. The second thing is in the 1-7-year-old population, in those younger children, obviously with an injectable that comes into play. But what we've heard kind of on an anecdotal level is they would use it, but only for their extreme patients, patients who have multiple food allergies, who have documented very severe life-threatening reactions with minuscule, minuscule amounts of exposure to their allergen, not sort of your quote, I hate to use the term, run-of-the-mill, but patients who might have a higher level before they hit that severity mark. That's kind of not the patient that they would target, really. Sort of the two-standard deviation out type patient is what we're hearing. Do you have a sense of how many children in that 1-7 age group see treatment with oral immunotherapy today, whether home brew or Palforza, the approved product? We don't have formal audit data of that. We do know Palforza, as you know, was only so much of a commercial success. What has been published is that that form of OIT was being offered to pretty much every family that had a diagnosis of peanut allergy. And more than 80% of the time it was turned down by the family because of the burden it represents, the adverse event on therapy, as well as the fact that an interruption of treatment turns out to be a setback. You have to go back. And that's a trait that's shared by both Palforza as well as other forms of OIT. So it's used. We don't think it's used very broadly. We don't have any survey data around it. But the limitations we saw of Palforza apply obviously to all forms of OIT, including home brew. OK. So we've honed in on kind of the opportunity, the unmet need. Can we talk a little bit about the data you've generated now, and specifically dig into response rates, safety, compliance adherence, all those kind of key metrics you're talking about that could differentiate Viaskin Peanut? Yeah, sure. So in the 1- to 3-year-olds, we published our EPITOPE data last year in the New England Journal of Medicine. Great efficacy results, 67% met the response rate versus 33.5% for placebo. The safety profile in 1- to 3-year-olds has been entirely consistent with what we saw in the 4- to 11-year-olds. Local application site reactions that rarely lead to discontinuation, they get better over time, really low rates of anaphylactic reaction. So the profile, from a safety standpoint, has just been so consistent across the board. Great efficacy results in 1 year. We just talked about the 2-year extension to that. One of the key data points for me is that after 2 years, 4 out of 5 subjects could consume 1,000 mg of peanut protein. That's about 3 or 4 peanut kernels. And they came in at a median baseline of 100. So that's a huge, huge amount of protection. You'd have to go so far out of your way to consume three peanut kernels. You'd almost have to do that on purpose. So the efficacy in the one to three, great. The VITESSE study is up and running as we speak about that. We spoke about that last year in the four to seven-year-olds. Can you talk about the efficacy safety in the 1-3 versus 4-7-year-olds? Yeah, no. The efficacy, as I said, in 1-3 was great. The 4- to 7-year-old, we did a lot of post-hoc analyses off of the original 4- to 11-year-old study. We modeled that every which way you could think of. And that is why the VITESSE study is in 4- to 7s. And it makes a lot of sense, just intuitively for the disease state, where younger patients just do better. It's a fact with whatever therapeutic area you're using. So we dropped down from 4-11 to 4-7. That study is ongoing. We just hit our 50% recruitment mark in the first quarter. We're on schedule for that to report out in the third quarter. We're really pleased with where we're going. Safety profile in 4- to 7s looked no different than any older age group, 8-11, 4-11. Safety is super consistent. Every reason to believe the 4-7 will have a good response also. Can you talk a little bit about how you measure efficacy in these trials? Because it's something a little bit unique in food allergy, the double-blind placebo-controlled food challenge, what that is and how you're measuring success, because the responder rate can vary depending on how they come in. Then you talk a little bit about the level of peanut they eat. Wrap it to some clinical relevance, what doctors and patients care about. Sure. So the food challenge is an incremental exposure to progressively larger amounts of peanut protein. You start at 1 mg, and you build up to 600 as an endpoint or 1,000 as an endpoint, depending on what study the FDA likes to see, 600 as a benchmark that's equal to about two or three peanut kernels. And it's double-blind. So on one day, you do a placebo. And our food challenge is in the placebo versus active. You really can't tell the difference. And then you come back, and then you repeat it with whichever you took the day before, either placebo or active. And you study the patients. And basically, you drive them almost to a full-blown anaphylactic reaction. And quite honestly, it's a pretty brutal process to go through. It's the best one we have today. And then that's how you check your responder rate. You do that at baseline and then at month 12. Do those reactions during the food challenge count in your safety data? No, they don't. None of the studies that we've conducted, that's just not the way the FDA counts them. As you could imagine, it's not really a product-specific safety. You said FDA cares about a 600 mg threshold. Do physicians care about? Is that a meaningful level? Yeah, that's absolutely meaningful, because you have thresholds that cut you off to get in. So if you don't react, let's say, at 100 mg or 300 mg, and then FDA likes to see a 2- or 3-fold jump in that. And that's absolutely clinically meaningful. Can you talk a little bit about reactive versus a listening dose or tolerated dose? We see it different ways. Why you chose the way you're measuring it? Yeah. So we chose that way based on the literature and our clinical endpoint. Different companies do it different ways. We felt like this was a very stringent way to do it. We pushed them pretty hard. And then you measure your level when you have a reaction. That's correct. So you measure the baseline, and then you measure it again at 12 months later. So there's no one that's right or wrong. It's just a preference. And FDA seems to have accepted either one right now. What stuck out to me when I saw the EPITOPE data in the 1- to 3-year-olds was the number of actual reactions in the study. You guys had a lower number of reactions. That seems to be where rubber hits the road to me. If I'm living my life and I don't have a reaction, that's a good outcome. But is it just that become a powering issue from a trial perspective, where if you only have a handful of reactions during the study, you'd have to have a massive study versus a food challenge? Do you mean in terms of the accidental peanut consumption? Yeah. Does FDA care about that as an efficacy, or is that a safety endpoint, or both? No, I think, yeah, it's a little bit of both. So that's not a powered endpoint that we look at in terms of accidental peanut consumption. But we've obviously looked at that data, and the rates are lower with longer-term exposure and in the first year relative to placebo also. Yeah. If I may add, back in 2016 or 2017, the FDA held an ad comm trying to see what's the right way to assess efficacy for food allergy treatment. Studies in the wild, well, you would see whether or not you actually have reduction in accidental exposure. The consequence of it would be difficult to run. They would have to be very large. So they chose to use the food challenge as a way to assess essentially those thresholds and clinical response. So what is observed in studies are interesting observations, but the studies are not powered to capture whether or not those accidental consumptions are meaningful, active versus placebo, or just simply for a number of reasons. There's a long history here with the regulatory background with Viaskin Peanut. Can you give us a summary of kind of what's happened at a high level and then what you're working on now to address those concerns that FDA had initially? Yeah. Our first BLA in children 4-11 with peanut allergy, we received a Complete Response Letter. This was in August of 2020, because the agency believed that because the product, the patch adhesion, which had not been well as in how does it adhere to the back of the child, had not been well characterized by the company, this was before our time. And the study had slightly missed its primary endpoint. 15% super superiority of delta to the 95% confidence interval was 12.4% instead of 15%. The agency suggested that had the patch adhered better, it maybe would have worked better. To make a long story short, we did not subscribe to that point of view. But this was mid-pandemic, with a product reviewed by the vaccine division at the FDA. They had other things to worry about. So we agreed to redesign the patch on the FDA's recommendation as to improve what would be the adhesion to the skin. Whether that will translate per se as higher efficacy remains to be seen. Now, VITESSE will answer that question here. We believe we have data to show that's an independent phenomenon. But that being said, that was the reason why we have a modified patch in the older kids. Not surprisingly, with the original patch in the younger kids, we blew away the primary endpoint, which we think just reinforces our point of view that adhesion here is not a marker of clinical response. Well, I think maybe if you could touch briefly, sorry to interrupt. The difference: FDA typically will see a patch to apply something to the skin, whereas you're an immune modulatory mechanism. That's not a light switch. That's exactly it. There's no stoichiometry here. There's no PK/PD relationship between allergen exposure and clinical response. So you don't have this tool you would have with a traditional patch that associates wear time to drug being delivered to systemic circulation and thus clinical response. That tool does not exist. More importantly, even if it did exist and it doesn't, we know very well from other forms of immunotherapy that's the repetitive exposure of the immune system to the allergen that drives clinical response, which is what our patch does. How important? Applied once a day. How important is the biomarker changes you guys are modeling then as well to show that the efficacy that you're seeing clinically isn't just by accident or anything? To piggyback on that, that it's not just a patch. It's an immune modulatory. Right. So we absolutely have tracked IgE, IgG4, and it follows traditional allergen immunotherapy patterns. So we know that the allergen is getting into the system. The immune system is reacting to it in an appropriate manner relative to other therapies in the past. Mechanistically, everything's lining up with the clinical results. Absolutely. Correct. And then so you mentioned the VITESSE trial in the 4-7-year-olds is ongoing now, 50% enrollment, on track for data, I believe, third quarter of 2025. Correct. On track for last patient first visit in 2025, correct. Yes. Then can you talk about what you need to do in the one to three-year-olds and anything else in the four to seven-year-olds that FDA had asked for? Yeah, sure. So actually, there are two separate BLA programs, completely distinct. And they're mirror image programs. So each of them have a 12-month safety study I'm sorry, 12-month efficacy study, EPITOPE reported out already. VITESSE will report out, as you said, 2025. And the FDA had asked us for supplemental safety studies for both of them. They were not looking for any specific safety signal. They just wanted to get to ICH guidance of about 600 exposed on active product. So those are the two comfort studies that we're talking about, COMFORT Toddlers and then COMFORT Children. Because the initial PEPITES phase 3 study was in 4-11-year-olds. So you take half those patients away from the safety database is why you need to run COMFORT Children. Is that the right way to think about it? They want 600. ICH guidelines are about 600 patients on active. The FDA wants to see about 600 patients, 4-7, on active. We'll have 300 with. 270 all in COMFORT Children. 400 on, we have 600 in VITESSE randomized 2:1. So 400 on active. We'll be adding 270 randomized 2:1 in COMFORT to get to roughly 600. When do you plan on starting the COMFORT trials? We'll be starting it as we are getting close to full recruitment with VITESSE, as to not compete with ourselves. One study, obviously, having a food challenge. The other one does not. So expect to start this study this year. A little bit easier. To run both of them at the same time. Is it a little bit easier to run a safety study than an efficacy trial? And can you talk about the nuances in what you're measuring? Yeah, they generally are, because the safety studies traditionally have not had the food challenges. They've only been six months in duration and 3-to-1 randomization as opposed to 2-to-1 randomization. Generally, they're more popular relative to the efficacy studies. So 6 months and 12. Six months, right? So shorter as well. Shorter as well. How do you think about the timelines between the two programs, parallel development paths? Is one in the lead? Which one do you think will end first? Does it matter? Does it make it easier from a regulatory perspective to have both packages at the same time or sequence them in any way? How do you think about is there a strategy to this? There's no absence of strategy. At the end of the day, it's the pace of recruitment that will drive which BLA will be ready first. So we don't have a preference whether 1-3 launches before 4-7, the other way around, or close together. They're likely to be close together. The data sets for both programs should be available in 2025, putting BLAs together in parallel. At this point in time, we're not handicapping one as more likely to complete or to be registered before the other one. We're sort of constructively indifferent. Just one more, as I'm thinking out loud, any potential advantages for having two separate BLAs for two different age groups and perhaps two different products or brand names and pricing strategies? Is that potential? The answer is yes. The biggest benefit is there's obviously embedded risk management. A supplemental BLA, the supplemental BLA is not worth much till the BLA is approved. Since we have two programs in parallel, both being independent BLAs means if one progresses faster, that's OK, because it does not essentially in any way reduce the attractiveness of the other program. So that was why we thought two BLAs in parallel was preferable. They're also two different patches. So that played better to the agency. Yes, it will be two different brand names. And given they've had the value proposition, which will be obviously embedded in the label, is likely to be different. We want to keep the option open of pricing that might be different. Interesting. And then as we're bumping up on time, the last question we always like to ask is remind our audience of your cash position and runway it provides in terms of both calendar and then also potential news flow. Yeah. We have $101.5 million at the end of the first quarter. Our guidance takes this to the end of 2024. Reality is it probably goes deeper than that for just good cost management reasons. The news flow will be the initiation of the COMFORT trial in toddlers, last patient first visit of VITESSE. So a year later will be a data readout. And that data readout sometime in 2025, plus year three of our treatment in toddlers, year two of the data read out in November of last year. So later on this year also, toddler year three will be reading out. So in all of that, our number of events that we think would be catalytic to financing but again, we're not announcing one right now. And we're keeping options open. Perfect. Well, a great overview. We're looking forward to the progress. Congrats again. Thanks for joining us. Thanks, Jon. Thank you. Thanks a lot. Appreciate it.