Hi, everybody. Welcome to the next session of H.C. Wainwright's annual Inflammation and Skin Disease Conference. My name is Joe Pantginis, Managing Director and Senior Research Analyst here at the firm. Very happy to have with us Celldex. Presenting for the company is Dr. Diane Young, Senior Vice President and Chief Medical Officer, Teri Lawver, Senior Vice President, Chief Commercial Officer, recent nice addition to the company, and of course, Sarah Cavanaugh, Senior Vice President of Corporate Affairs at Celldex. Guys, thank you very much for being here. Look, having covered Celldex for well over 15+ years, it's so completely gratifying to me to really see the progress that you've made and really being on the cusp of potential approvability of barzolvolimab, which will be the bulk of our conversation today, in about a year or so, depending on how the studies go, with urticaria, sorry, being in phase III's. With that said, I of course want to make sure we dive right in based on time today and hit the salient points on the time that we have. Again, ladies, thank you very much for being here. Thank you for having us. With barzo being your lead asset, obviously, and it's been in a nice development program, I think there needs to be a quick reminder, plus a little bit of a compare and contrast. I know sometimes it's difficult to talk about the competitive landscape, but this is at the forefront of investor minds, obviously, as to the antibody's mechanism of action and also, relative, I said, to the competitive assets also targeting urticaria and beyond. Yeah, I'll start. barzolvolimab is an anti-KIT monoclonal antibody, and this is a novel mechanism of action that is really targeting the root cause of the diseases we're dealing with, which is mast cells. KIT is a receptor that is expressed by mast cells, and it's really critical for their function and survival. barzolvolimab, with a unique mechanism, blocks the KIT receptor and leads to mast cell depletion. This is a novel mechanism. The other drugs that are out there for urticaria are targeting things that are triggering the urticaria, various IgE, or they're targeting mediators such as IL-4, IL-13 with Dupixent. barzolvolimab is going for the mast cells itself. It's a very broad and novel mechanism. No, that's really helpful. Of course, there was additional news with Dupixent today, so maybe we'll touch on that a little bit later. Look, I guess part of the bulk of this conversation in leading up to the current phase III's, data are always key. I was hoping we could get a bit of a review of the phase II data set, or I should say even broad phase II data set, in CSU as well as ColdU and SD, that were so incremental in driving your quickly progressing pivotal programs. We conducted phase II studies in CSU and CIndU. In CSU, we studied antihistamine-refractory patients, including those who had had prior biologics and other advanced therapies. Really, in that study, we saw that barzolvolimab has rapid, profound, and durable effects on urticaria symptoms. We reported very high complete response rates, so we had up to 51% complete response rate at week 12, meaning no itch, no hives. When we continued the therapy out to week 52, that went up to 70%. Even off therapy for seven months, we still had a 41% complete response rate, and that's really unprecedented. In addition, the other endpoints in the study, notably angioedema and quality of life, also showed really dramatic improvements. We did a study in inducible urticaria, which is urticaria which is triggered by various conditions. There we studied cold urticaria and symptomatic dermographism, and the endpoint for those studies is provocation tests and the ability to provoke the urticaria. We saw that we had statistically significant benefits in terms of patients having negative provocation tests on barzolvolimab, and that was in both cold urticaria and symptomatic dermographism, with both doses of barzo in the study versus placebo. As well, we showed benefits in terms of Urticaria Control Test and quality of life. Really nice clinical responses, as well as the provocation tests. No, that's fantastic. Maybe just a little more colour, then I know will help Teri's conversation later as her job gets more broad as well, is the durability component. I'm hoping you can just maybe dive into that a little bit more, especially when we consider the landscape. Yeah. The durability, so two parts of that. In the CSU study, we treated patients for 52 weeks, and then they went off therapy for six months. In that study, we observed that patients really maintained their response, and when they were recurring, they were coming back at a milder level of disease. This is totally novel. Other drugs in this space don't do this. It raises the question about whether we're seeing some sort of disease modification here. The companion to the durability that we saw in the CSU study was in the CIndU study. We had a different design where after 20 weeks of treatment, they went off therapy, and then if they recurred, we allowed them to go back onto barzolvolimab. Part of the results of that study that we recently presented were that with retreatment, you get the exact same response as you had at the beginning. That really sets us up with some flexibility in the future as to how physicians will treat patients. No, got it. I guess, again, with the potential for disease modification here, not to repeat or re-emphasize, and I don't want to overstate unless it's really true there is, targeting KIT as the core target here as the key area of disease. I'm not having you to repeat that, but it just seems pretty obvious, not real scientific term there, but it's a nice correlation. Yeah, I agree. It's really interesting, and it definitely differentiates us from the other agents so far. Got it. It's interesting to add to that when you. Please do. Look at the biology, tryptase is a marker of mast cell burden. For these patients on study, at the end of study, if their disease is back, it's typically also milder in form. When you look at their tryptase, their tryptase levels are now much more normalized, whereas when they were at baseline, they were much higher. We're seeing that change in biology too. No, that's perfect. I appreciate those comments. Look, as I alluded to earlier, all eyes right now are on the fact that you guys are a pivotal stage company. That brings in a lot more eyes on the investor front and, of course, building interest in the physician community that might not necessarily know about Barzo or broadening the experience there, again bringing in Teri's future responsibilities and what she's also building now. With that said, your phase III CSU data are due approximately in the Q4. Of course, in biotech, things can waver a little bit. One of the things that we've been impressed with is that this study has enrolled quite quickly. I was wondering, first, can you comment on that? Even more importantly, can you discuss the endpoints of the study and how we, the Street, and even physicians should benchmark the success of this study, and what really represents a positive outcome beyond the, of course, required stat sig? Yeah. We were very pleased that our enrollment went so well and that really completed six months of where we had guided, and really faster than the competitors' trials. These were very large studies, and these are the largest studies that have been conducted in this antihistamine-refractory population, including patients refractory to advanced therapies. We think that this really speaks to the unmet need out there. There are clearly a lot of patients in need of new therapies. There was also great enthusiasm for the drug. We were very gratified by the participation of both allergists and dermatologists in the study. We were really pleased with how well it went. I would also say that our operations team did a fantastic job, and we had a CRO who has had experience in this area, so all these things really work together. In terms of the endpoint, so our endpoint is the mean change from baseline in Urticaria Activity Score 7, which is the daily diary that patients do, and this is a traditional endpoint for CSU, as you mentioned. We've sized the study. It's 90% powered to see a 10-point change in the UAS7 between placebo and active. That being said, and I would say it's 90% powered to do that in the omalizumab-refractory group. It's overpowered in a sense for the larger group of the study. I would say that when we are looking at the results, we would really like to see similar results to what we saw in phase II, which we believe are differentiating. We're really looking for high complete response rates because we believe that complete response is the most important thing for patients, no itch, no hives. We're also interested in looking at the group of patients who had prior omalizumab and were refractory to omalizumab because that's really an area of unmet need. No, that's great. Look, I think I'll ask a devil's advocate question, but before I do that, if you could just give us a quick reminder of the size and design of the study, because obviously you mentioned about omalizumab-refractory patients as well. Yeah. We had 1,900 patients on the study. It looked at two different dose regimens of barzolvolimab and placebo. It has a six-month placebo control period with a 12-week endpoint, and then the patients go on to active treatment for another 36 weeks. We have tried to keep all elements of the study very similar to what we did in phase II in terms of inclusion, exclusion criteria, endpoints, things like that. The only real difference is that we added a loading dose to our two dose regimens, and that was based on data that we saw in phase II. Okay. Got it. Sort of the devil's advocate question, and you see a lot of these and, of course, it's not related, so it's loose analogy here. In cardiovascular diseases where, okay, there's a bogey that the Street's expecting. You're talking about being powered for a 10-point difference in UAS7, and it's like, well, what happens if you come in with a nine, eight, or a seven? It's still clinically meaningful, and you could still hit very important numbers, but again, it's like you always have versus cardiovascular MACE, where the Street might have wanted a 15% impact on survival, and they got a 13%, which is still doctors say that's awesome, but the Street got disappointed. I guess, there's this balance that we're trying to hit here, even though the phase II data support what you're looking for. Again, just playing strictly devil's advocate. I think we've tried as best we can to keep everything as similar as we can to phase II. We tried to monitor the study very closely going along. Beyond that, we have to see what happens. No, of course. I get it. It's always to me, just the constant balance of physicians, what they're looking for and what investors are looking for, and sometimes they're different in the interpretations. Again, just very encouraged about what you've shown so far. Thanks for that. Look, Teri, like I said, you've got a lot of things going on in the background since you've joined, obviously, and your position is going to be really growing in prominence, hopefully as we look towards potential approval. phase III data are not too far off. I think a key point to this discussion today and beyond, obviously, is the commercial profile of barzo. This really also needs to include a view towards the competitive landscape, which we already started to touch on, including Novartis. Like I said, there was additional news today with Dupixent and the role in following drugs like XOLAIR. Little long-winded sort of intro on my part, but I guess from the baseline, what kind of market sizes are we looking at for the two top indications here with regard to CSU and cold? We see significant headroom for growth in these early indications. If we take CSU in the U.S. just as a starting point, approximately 1.8 million people in the U.S. suffering from this disease, but only 32% receiving a proper diagnosis, and that diagnosis can take anywhere from seven months to three years when it happens. The new entrants into the category, as we've seen with other I&I diseases, typically create a tailwind for both speed of diagnosis and movement on to advanced therapies. With those tailwinds, we see the worldwide market for chronic urticaria advanced therapies, so that's CSU and CIndU, reaching peak sales of $12 billion with potential upside. Got it. I think there's another aspect of numbers here and potential disconnects about how investors view the size of these markets when they hear these indications that they may not have heard about or are just learning about. I think those comments are extremely helpful. Of course, this talks to physicians' potential use, but also the understanding of investors. Where do you think barzo, at least initially, may fit in the treatment landscape with regard to targeted populations or stages of disease, or what have you? Because obviously the phase III's right now, excuse me, include omalizumab-resistant patients. There are two large and growing patient populations where we believe barzolvolimab is really uniquely positioned to address the unmet need. The first of those is in first-line advanced therapy, so patients who are refractory to background antihistamines, who are presenting with severe disease and angioedema. If we look at the angioedema scores from our phase II data and not only the overall scores, which were 65% angioedema-free at 12 weeks, and that deepening to almost eight out of 10 patients at one year. When we look at the placebo-adjusted delta on angioedema-free, it's more than double what's been seen with any historical therapies before us. When we quantify that first-line opportunity, in our phase II studies, we had 36% of the population with both severe disease and presenting with angioedema. Even if we assume the broader population is, say, half as severe as those who enrolled in our studies, that's still 15% of the first-line market. Keep in mind, for angioedema, these patients have historically been treated with chronic corticosteroids, oral corticosteroids, and the entire community, both the physicians and the CSU patients, understand how toxic that is. They really need an alternative. The second opportunity for entry point is as the preferred therapy of choice for all second-line advanced therapies. For patients who have tried any of the current three approved advanced therapies and are still symptomatic, barzolvolimab offers a really important option, being, we believe, potentially the first product with, in our label, demonstration of efficacy in a bio-refractory population, as well as efficacy regardless of IgE levels. When we speak with physicians and patients who are at this critical juncture of having tried an advanced therapy, still suffering with their symptoms, barzolvolimab can take the guesswork out. Give people a lot of confidence in the opportunity. When we quantify that second entry point, we assume, say, a 50% flow-through from first-line advanced to a next therapy in a given year, which is consistent with what we've seen both with XOLAIR in this category, but also what we've seen in other I&I categories. That would make the second-line plus advanced therapy market eclipse first-line from a market opportunity within the first few years. Those two really nice entry points for barzolvolimab. Okay, got it. You know what? That links nicely, I think, and, of course, this is open to all of you as well. You talked about the landscape, where it would fit here, and to me, there's also this, I don't want to keep saying disconnects between physicians and investors. Docs always talk about having multiple tools in the bag. It's not like you're going to supplant Dupixent or Novartis or what have you. They want multiple tools. They're going to look at it at different stages, use it in different patient populations as you build market penetration for the indications you talked about. As your education moves forward, of course, not just on the phase III data, which will be absolutely critical, I also see the linking again back to the underlying mechanism of action with regard to the disease modification. Maybe you could talk to the multiple tools in the bags right now and sort of get the initial doctor feedback from the current phase II data and as you're looking forward and doing a lot of your initial research here? Let me start addressing the unmet need and where barzolvolimab fits even in this competitive landscape, and then maybe Diane can talk about the uniqueness of the mechanism behind that. Even with these entries, as we say, we believe that's a tailwind for barzolvolimab in terms of bringing people into treatment. Now, there are three really important areas of unmet need that barzolvolimab can address in a unique way. The first, and Diane touched on these, but the straight-up differentiation in three critical areas that we're hearing from physicians and patients are absolutely pivotal. First is those patients who are in complete response, not UAS7 less than six, but zero, so absence of itch and hives. Barzolvolimab in our phase II trial was the first trial to show a majority of patients in complete response at 12 weeks. The second area we think about is the deepening of response, right? That deepened to 71% at 52 weeks, and then that off-drug durability. Differentiation, deepening of response, and durability. We see that across complete response. We see that in return to normal quality of life, which is the number one factor that patients point to in terms of what they're looking for in a treatment. For those patients with angioedema, again, complete absence of angioedema, 65% at 12 weeks, eight out of 10 at 52 weeks, and then even off treatment at 76 weeks, still a majority angioedema-free. That differentiation, deepening, and durability is a really unique profile, and as Diane alluded to, where we have the option to show off-drug durability, right? Typically, I&I drugs, when they talk about durability, are talking about on-drug durability. We're seeing the same level of complete response off drug that other companies are seeing on drug, right? That gives us an immense amount of optionality in terms of utilization paradigms, in terms of differentiation with the payers, and in terms of really filling big needs that while these other new therapies are really good additions to the armamentarium, there are some things they won't be able to address that barzolvolimab will. Okay, just making sure, because you alluded to Diane a little bit, making sure you didn't have any additional comments there. No, just to reiterate, I think our mechanism in depleting mast cells is really targeting the root cause of the disease. Omalizumab targets IgE, which is one trigger. Dupilumab targets IL-4, IL-13, which is a mediator and affects a subset of patients. BTK is a pathway that's downstream of IgE receptor. We think we have a broader effect. I'll just reiterate, I think physicians are very excited about having different options for CSU. We're seeing that now with new drugs becoming available after only having omalizumab for a long period of time. They definitely talk about how it's all about discussions with their patients, and they're going to take into account how severe are the patients, what are their symptoms, how convenient are the dosing regimens. They're really happy to have new things, and they're pretty enthusiastic about barzolvolimab. No, perfect. I appreciate that. I'm going to ask the broader question here that sometimes as a company gets closer to filing or has filed or is awaiting FDA decision has negatively impacted some companies in the past. We won't mention any names, but the broader question here is how are your manufacturing preparedness here with regard to barzo and being able to hit the ground running? Yeah, I can say the team is working very hard on that. We're obviously working with contract manufacturing, and we're really monitoring the whole process. We're preparing to enter the market with a prefilled syringe, and then we're developing plans for an auto-injector to follow that. Got it. It's easy then to just plug and play with your CROs to be able to get more slots available and pre-plan for those. So far. Fashion. Yep. Okay. Again, I'll just stick to the broader profile of the company right now, and then if we have time, I'll ask another question here. How we doing? Yep. Over the years that I've been covering you've always had and been able to keep a big war chest going with regard to cash on hand. I'm hoping you can sort of discuss that. You guys obviously just did another sizable raise, over $300 million, which again, shows that you continue to attract important investment into the company. I'll also maybe so discuss that. I would also link that to providing leverage in any potential, or upcoming, or ongoing BD discussions. That's the second part of the question with regard to what are your general views towards BD at this point? Sure. As you alluded to, we ended 2025 with $518 million in the bank, and our cash guidance at that point was through 2027. We just recently completed a raise and brought in an additional $345 million. I'm sure we'll update our guidance when we report out Q1 relatively soon. From that perspective, it was fantastic to have that money raised. It was a great mix of some current investors and some new investors who've been very excited by the story. I think what really drove that excitement was seeing that enrollment get completed early, and it certainly spoke to the enthusiasm around the program. Also, as you mentioned at the start of the call, it brought those top-line results into the Q4 of this year, so we're really all looking forward to that. From a business development perspective, it certainly always makes sense to have cash on hand. You know how important that is. We have been very clear that we want to take this drug forward on our own in the United States. It's part of why Teri is here, and we are working through all those pieces. We'll certainly be smart. We'll look at the opportunities that are out there and evaluate them as they make sense, but we are really looking forward to launching this drug. Oh, perfect. You know what, I am going to ask my last question because again, it's also different personalities in the investment community. I can't say 100% focus is on Barzo right now, but it's very high. You always have the mantra in people's heads that's saying, "Okay, what have you done for me lately? Got Barzo going on, what do you have going on in the background?" Maybe you could take a minute or a minute and a half just to maybe discuss your pipeline assets, at least from a high-level standpoint. Sure. Let me do two things. I'll have Diane quickly talk through 622. Maybe what we can do is I can end by capping through the milestones for both barzolvolimab and 622. Perfect The rest of the year. All right. Yeah. We're very excited about CDX-622. This is a bispecific antibody that targets TSLP as well as stem cell factor. Stem cell factor is the ligand for the KIT receptor, so that part of it is a different way of targeting mast cells. We have entered this into phase I, which is fully enrolled. We presented some of the single ascending dose data, and it looks very promising. We will have the multiple ascending dose data later this year, and we have initiated a proof of mechanism study in asthma. Because we believe with the two targets that pulmonary diseases are a good direction to go with this, but there's actually a lot of potential. We're really excited, and I can tell you that our Chief Scientific Officer, Tibor, has a number of other things behind that that are not clinical stage yet. Absolutely. Tibor has always delivered for the long term, coming up with assets. He has. If we look at from a milestone perspective, for barzolvolimab, we really focused on CSU and on inducible urticaria. As we said, you'll see top-line data from the phase III in CSU in Q4. We also will continue to enroll to the phase III inducible urticaria study. We recently completed enrollment in two phase II studies, one in Prurigo Nodularis and one in Atopic Dermatitis. The PN data is expected in the summer of 2026. The Atopic Dermatitis data is expected in late 2026. You're going to get PN. You're going to get both phase III studies in CSU reading out at the same time in Q4, to be followed by the Atopic Dermatitis data. Diane mentioned the 622 study, so you'll have the phase I multiple ascending dose, healthy volunteer data, and then you'll also have the sub-Q multiple ascending dose data. That'll all come around Q3 of 2026. Lots of opportunities to look at data and add to the story. No, absolutely. Look, we're great on time here. Teri, Diane, Sarah, thank you so much for doing this. Great commentary. Wish you the best of luck coming into the phase III data, and really a lot going on with all the catalysts that Sarah just mentioned as well. For those on the call here, please enjoy all the other sessions, of course, for our fourth annual Inflammatory Skin Disease Conference. Again, ladies, thank you very much. Thank you, Joe. We really appreciate the time. Thank you.