All right. Good morning, everyone. Welcome to Guggenheim Healthcare Innovation Conference. Our next presenting company is Celldex Therapeutics. We have a few executives from the company here in our room. We will be chatting here with Tibor Keler, who is the Chief Scientific Officer. We have Diane Young, who is the Chief Medical Officer. We have Sarah Cavanaugh. She's the SVP Corporate Affairs. I have prepared a list of questions for you guys, but maybe I can hand it over to you or Sarah. Why don't you make some opening comment, just recap for us some of the upcoming milestones that you have. You just had earnings yesterday, and then we'll go into the Q&A. Sure. Sounds great. Thank you for having us. We really appreciate it. 2025 has been an incredibly exciting year for Celldex. I think most notably marked by data across our urticaria programs. We presented 76-week data out of the CSU program, where we saw phenomenal efficacy, including post-treatment. Just last week, we had data from our phase II inducible urticaria study in Symptomatic Dermographism and Cold Urticaria. That study is really unique. It is a very large randomized placebo-controlled study for those indications. The data there, which Diane will speak to later on, was also fantastic. That has really set us up nicely for late-stage studies in both of those indications. As you know, the phase III studies in CSU are ongoing, and we will initiate a phase III in inducible urticaria in December. On the other part of the pipeline, we had data out of the CDX-622 program a couple of weeks ago, which Tibor can speak to. Very, very well positioned for a busy 2026. Very good. Thank you for that. I want to double-click on the CSU long-term data that you have presented, because at least we have gotten very positive feedback from physicians, specifically as it relates to the off-treatment durability that you are showing. I would love to hear from you. How are you putting those data in context relative to historical norms in the disease? What are you hearing from physicians? Is that helping you from an enrollment standpoint? I'd just love to hear from you on those CSU data. Yeah. We presented the 76-week data from the study. The remarkable thing about the study, we had already seen that we have very high complete response rates. In our 52-week data, we have probably the highest complete response rate that's been seen in other studies. With the 76-week data, we had the period off-drug follow-up. In that study, we showed that seven months after the last dose, we still have a 41% complete response rate, which is really incredible. In talking to the experts, it's really unprecedented, and people are very excited about it. They use terms like disease modifying, and they're trying to understand it in various ways. I think it does help enrollment. It does help kind of the excitement. We're really very, very excited about that. How would you put that in context to sort of a historical norm? What do we get with currently available options? Yeah. Xolair, if you stop Xolair, it comes back within a few weeks. Remibrutinib, we have not seen follow-up data, but we understand it has a short half-life and that symptoms come back if you stop taking it. Dupixent has a lower response rate. They have possibly some long-term follow-up, but they have not followed it for very long in those studies. It really is unprecedented. Got it. Got it. Obviously 76-week data now, a lot of safety data, which has been very consistent. How is the perception of the safety now, specifically in context of this disease-modifying ability that this drug has? Yeah. So I think that the 76-week data really was very satisfying to everybody in terms of what it says about our safety profile. Barzol is really very well tolerated. The side effects that we get are mild. They're really more cosmetic. They're not medically serious. Importantly, with the 76-week data, we did show that they are reversible. The hematology results in terms of the neutrophil counts, we see a very consistent pattern of decrease, which we did see return back to baseline. I think the long-term data is very, very positive. Got it. Could you maybe then talk about the phase three programs, or the phase III program, the two studies that are up and running? How is the enrollment going? What are some of the key features of that study that might be different than the phase II study? In terms of the studies, there are two identical large studies, about 900 patients each. They are randomized placebo-controlled studies. They look at two different dose regimens of barzolvolimab versus placebo. I will say that they are in every way very similar to the phase II studies. They are the same inclusion-exclusion criteria. They are the same endpoints. The difference really is that we have added a loading dose to the two dose regimens. That is the biggest difference. Got it. Got it. Anything on the enrollment front, Sarah, maybe when might you be able to sort of provide an update on the enrollment and how are you thinking about communicating to the street? Sure. It's going exactly as we've guided. We've guided that we'll have data that will complete enrollment by middle of next year in the summer. Got it. Okay. Are you talking about the expectations from that study? Are you sort of, or is it too early to tell? Just trying to understand what are certain scenarios in play when it comes to data for phase II. I think we'd like to see as good as what we saw in phase II. We'd be very, very happy with that. Got it. In terms of the positioning, again, I want to again stress on the off-treatment durability that you are showing. What is the perception now or how you are thinking about positioning of the drug? Where exactly you think the uptake will be initially when you launch it and how it will evolve? I think as we look at the data and as we talk to physicians, really it's going to be about the patient and what the patient's needs are. These patients really suffer. These are serious diseases with significant impacts on their quality of life. For moderate to severe patients, it starts a conversation about what they want out of therapy. I think we're really trained to think about lines of therapy, one, two, three, and how you move through them. What we're hearing as we're talking to physicians is that this enables them to have conversations with their patients about what they want out of a treatment. We think there's lots of opportunity there. We need to see what the data looks like from the phase III, but we feel very well positioned from that perspective. Got it. Very good. On the inducible, I think there was this recent update that you provided. Can you just review for us what are some of the key features of that data? Also touch upon, are you seeing similar off-treatment durability in that population as well? Yeah. So this was at the ACAAI meeting last week. Dr. Jonathan Bernstein presented the results of the 20-week data that we had. That study was designed differently than the phase two urticaria study. We had a 20-week placebo-controlled period. Patients went off drug at that point, but they had an open-label extension that they could enroll in. That was intended to get retreatment data. What we showed at the meeting was the 20-week placebo-controlled data, which was the longest placebo-controlled period that we've shown. I just want to remind people that the study is really kind of groundbreaking because it is the largest randomized placebo-controlled study that's been conducted in inducible urticaria, in Cold U, and in SD. The primary endpoint in this case is complete responses defined by negative provocation tests. What we showed was that the Cold Urticaria patients, about two-thirds of them, had a complete response at 20 weeks, and about half of the patients with Symptomatic Dermographism had a complete response at 20 weeks. Also, the safety profile was very consistent with our other studies. Got it. And then you're starting a phase III study next month, right? That's the official guidance. Is it one study or is it a broader program? What are you able to share about the study? Yeah. So it's going to be one study with both forms of inducible urticaria that we studied. So Cold Urticaria and Symptomatic Dermographism. It's a randomized placebo-controlled study, and we're looking at complete response according to provocation tests as we did in the phase two. Okay. Are you also doing a loading dose here? Yes. Okay. Okay. What dose regimen are you able to say? The dose regimen, are they similar to the CSU? Yeah. So we're going to have a loading dose, a little bit different. We're having a loading dose of 450, and we're using the 150 every four weeks. Okay. What are the timelines? It It was just too early to say for CIndU. We haven't guided, just that we're starting it soon. Okay. Okay. Fair to assume that CSU, you file first and then basically use this as an SPLA at some point to get the approval. Yeah. That's the point that it's a much smaller study than the CSU was because we're using the safety database. Yeah. So there is nothing approved for CIndU per se. How big is that opportunity relative to CSU? About a third of the patients. There is nothing approved for CIndU. Yeah. CIndU is more on Monday. Okay. Regarding the other two studies, so you have a PN study and atopic dermatitis study. I think the data are going to come in the second half of next year. Could you just talk about the expectations from both? PN, at least we have seen some data. AD is completely novel from a biology perspective that needs to be de-risked. What are the expectations for these two studies? Yeah. So for PN, as you said, we do have direct data that we have seen efficacy in prurigo nodularis. We saw it in the first inducible urticaria study with one patient who had PN and completely resolved lesions after a single dose. We did the phase IB study, which again was a single dose intravenously, but we saw very rapid reduction in itch. And also we started to see lesion healing fairly early. I think in terms of this phase II study, it is subcutaneous dosing, but we really hope to see responses that are, we say, at least as good as, if not better than what's out there now, which is Dupixent and nemolizumab. For the AD? Oh, yeah. For AD, we have less direct evidence for that, but we do think that the profound effect that we have on itch in the PN study should translate to AD also. There we are thinking that positive results from that study would put us between Dupixent and JAK inhibitors. Dupixent, very commonly used, very popular. We think we're going to have better efficacy and a safer profile overall than the JAK inhibitor. Yeah. For the AD study, are you enrolling bio-exposed or Dupixent-exposed patients in that study? Anything you can say about, would you expect similar consistent response irrespective of the bio or previous biologic exposure, just like you get in CSU? We are allowing people with prior biologics in that study. It's a little early to say. I mean, we would think that it would be positive, but I think we're learning more and more about the different subsets that are present in AD and things like that. It will certainly be interesting to look at. For the AD study, are you doing a loading dose here in this study or? Yes. There is a loading dose. Okay. And then both the studies are going to read out next year? Yes. Second half. Second half. Second half of next year. Okay. So beyond CSU, CIndU sort of is within that AD. Are other indications that you are thinking about or just thinking about how you expand more in other areas with barzolvolimab? No, we're definitely thinking about a lot of other indications. I think different conditions related to itch are logical based on PN. I think we did have the results with EoE that showed that mast cells are not really a driver in EoE, but we did show that we depleted mast cells in the GI tract. There are potentially diseases there. I mean, there are a lot of diseases that we could potentially look at. Got it. Got it. This is where the bispecific portfolio can really come into play though, because a lot of indications are multifactorial. With the bispecific, we have an opportunity to target different realms there. Okay. Okay. Since you mentioned about bispecific, I think there was some new data for the first time that you had generated and presented on 622. I would love to sort of understand from you the mechanism, why it is unique, what is unique about it, and if you can put the data in context for us, Tibor. Yeah. So our bispecific called CDX-622 targets both TSLP and stem cell factor, stem cell factor being the ligand for KIT. In the context of bispecifics, we thought it would be advantage to target the ligand instead of the KIT, avoiding any potential cross-linking that could occur when you're binding multiple targets. Just a little word about stem cell factor. It is more nuanced than KIT. I mean, in principle, blocking stem cell factor should result in a similar effect as blocking KIT. But stem cell factor comes in two different forms, a membrane-bound form and a soluble form. And they have different functions as it relates to KIT-related activities. By targeting soluble KIT, which is what the stem cell factor antibody that's part of CDX-622 targets—only the soluble form of stem cell factor—it might avoid some of the KIT-related adverse effects that you might expect with broad KIT inhibition that relate to hematopoiesis, spermatogenesis, pigment changes, which are thought to be driven primarily by the membrane form of stem cell factor. We are really excited about this. We are certainly excited about the TSLP part of the molecule, which has been validated, of course, with the results from tezepelumab in asthma and now newer indications. We believe our antibody is very similar to tezepelumab based on our preclinical studies. We think combining these two pathways, so this alarmin that drives Th2 inflammation very potently and separately mast cells, which can contribute to that inflammation, really puts CDX-622 in a unique position for a number of different indications, pulmonary and fibrotic allergic indications. We just presented on single ascending dose data from the Healthy Volunteer study, which is a very standard approach for drug development. This was dose escalation from 0.3 mg-9 mg per kilogram IV with our first formulation. Importantly, we had really good exposure. mAb-like pharmacokinetics, as we have introduced YTE, half-life extension into the molecule. We had no immunogenicity, which is a critical hurdle for bispecifics to pass. Of course, on the safety side of things, we observed really no signals of adverse events, especially those that you might consider from inhibiting KIT, such as hematopoiesis. On the safety side, it looked great. On the mast cell side, we are able to look at tryptase as a way to monitor for inhibition or depletion of mast cells. We saw clear evidence of sustained and significant decreases in circulating tryptase levels. Really pleased with the initial outcome of the phase I Healthy Volunteer data so far. Got it. So given that you're going after the soluble form of SCF, right, is tryptase the right sort of biomarker for us to look at relative to what we saw with barzol? I think, yeah, there's a danger of comparing this molecule to what we see with barzol. I do think tryptase is still a very useful biomarker. It tells you systemically that you are having an effect on mast cells. It doesn't necessarily speak to which mast cell populations are being impacted and quite how much. There's still a lot more work to be done. One speculation might be that certain mast cell populations might be affected much more than other mast cell populations. That's yet to be seen. Really importantly, while we aren't able to really appreciate the inhibition of TSLP in the Healthy Volunteer study, its impact on inflammation and driving those factors is also going to be critical to this molecule. That's something we plan to get out of our early asthma study. Got it. These were single ascending, right? I think you went up to 9 mg per kg. How should we think about the data in the mAd cohort where you might have higher exposure? Do you think some of these biomarkers could have even more profound effect, or what we are seeing is enough? Yeah, certainly. There will be greater exposure with the multiple doses, so it'll be additive. We certainly expect that that could drive, for example, the tryptase levels lower. We'll certainly be interested in seeing how that impacts the safety profile, which we hope continues to look really, really well. Yeah, we're still, this was step one. We still have the multiple ascending dose as well as the subcutaneous formulation, which we're introducing into this trial as well to read out next year. Got it. How are you thinking? I mean, I know you are going in asthma, but if we step back, what is the developmental strategy here? Is this the asset that could actually even go into some of the GI areas that you just mentioned? How are you thinking about indications? The way we're thinking about developing this program is initially get through the phase one proof of mechanism, demonstrating that we can impact both the TSLP and the mast cell pathways that we think we can do in this small asthma study that we're doing, that we continue to have low immunogenicity, good pharmacokinetics, and exposure. These are all important hurdles from a bispecific point of view. As far as the indications go, I mean, clearly both pathways are important in asthma. That's been demonstrated. That is an indication to consider. We are very interested in appreciating whether or not this molecule opens up doors for younger patients as well, younger patient populations. If we're not seeing impacts on some of the reproductive biology, then food allergy is one of the indications we're interested in based on the role of both mast cells and TSLP in that indication as well. A lot of things on the table. There's obviously a lot of development going on in the TSLP space and following what others are presenting as well. Got it. Yeah. I think there's definitely a lot going on in the food allergy new space that I think is opening up. On the GI side, is this an asset that you could go there or you most likely stay in the respiratory and some of the allergic area? No, certainly. I mean, we're open to a number of different opportunities. We are also working within our pipeline on other bispecifics. One thing that's really important about 622 is it really paves the way for a pipeline behind it with additional bispecifics targeting stem cell factor and other really validated components. With regard to the asthma study, what is the goal here? Is it to sort of drive teze-like efficacy or just trying to understand? The primary endpoints are really biomarker related. We like asthma because the data with TESI gives you very clear endpoints regarding some of these biomarkers. We would like to see similar effects with 622, as has been shown with TESI on those biomarkers. In addition, we're planning to collect sputum samples from these patients, which will really tell us about what's happening at the lung. Getting clear evidence of the impact on mast cells and some of these other biomarkers in the lung is going to be helpful for deciding on our next indications. Got it. Very good. One question on the competition more related to Novartis. I think they are launching remibrutinib. I think the company is saying that, hey, look, the market expansion is possible because now they can talk about it. What is your view on remi and the market dynamic? Do you think the market expands with more people talking about it? Absolutely. I think if you look at the numbers that Novartis has been providing around the CSU market, they just continue to go up, go up, and go up. We feel like the data that we've seen to date for barzolvolimab positions barzol very well within that market. Got it. Very good. Maybe one more question. How is the balance sheet looking? How is the, yeah, what's the cash position and then the runway? Sure. So we reported yesterday with $543.2 million, which gets us through 2027 and a number of these important milestones. 583, right? 583. Is that what it is? Sorry. Very good. Thank you so much. It was very good, helpful. Thank you. Thank you for your time. Thank you.