All right, good morning, and thank you so much for joining us for our second day of our first annual I&I Summit. I'm Jeroen Warburg with the TidyCal and Biotech Team, and it's a great pleasure to moderate the next session with Celldex. With us today really needs no introduction: Anthony Marucci, Founder, President, and CEO; Tibor Keler, Founder, Executive Vice President, and Chief Scientific Officer; and Diane Young, Senior Vice President and Chief Medical Officer. Team, thanks so much for joining. We appreciate it. Thank you, Jeroen. Appreciate the invitation. Yeah, we have lots to discuss. I want to talk about, we'll talk about the recent CSU data. We'll cover the ongoing phase III in CSU, then move on to PN and AD, and then talk about 622. We should definitely cover the lay of the land of Celldex, since you have a lot going on into next year. Maybe just to start, you just showed the 76-week phase II data from the CSU phase II, showing a 41% complete response rate. This is seven months after stopping barzolvolimab. This is essentially durability of therapy. A 41% response rate is something that you see on CR rate. It's something that you see on Xolair. I believe it's higher than Dupi. This is kind of a ruxolitinib, almost like CR on therapy. Maybe can you put this in context, maybe competitively with other drugs? Why is there such a durable remission, given that mast cells do come back? I can start. Basically, this data is unprecedented compared to other drugs. As you mentioned, seven months after the last dose of barzolvolimab, we have a 41% complete response rate, which is similar to what other drugs achieve when they are on drugs. I would say in terms of the competitors, Xolair, if you stop Xolair, it returns within a few weeks. We have not seen what happens when you stop ruxolitinib. We know that it's a drug with a short half-life, and we hear anecdotally that if you stop taking a pill, even while you're taking it, you get symptoms back. We have not seen their long-term follow-up. Dupixent had very modest efficacy and does appear to be somewhat slow to come back, but they do not have very many weeks of data, and it's a modest improvement to begin with. We really think this data is unprecedented, as I said. I'll let Tibor answer why it's happening. We know it's still maintained after the drug has cleared. Seven months, certainly, we know the drug has cleared. We also have data that mast cells are back based on the tryptase levels coming within the normal range at week 76. We've talked about these data with KOLs. People have commented on this clearly being indicative of disease modification. Whether we've modified the mast cells that are returning is unclear. We don't have direct evidence of that, but we're extremely pleased with this long-term effect and think it'll make a big difference for patients. As you think about future studies, how would this translate into what you can do maybe in the OLE after the phase III? For right now, we're really focused on getting the efficacy and safety data that we need with a certain duration of therapy. The OLE is designed to get additional follow-up information as well as explore retreatment. We think that when the drug is approved, that out in the community, they will play with some of these things, just as they do now with Xolair, for example. They're changing the frequency and the duration. I think it's something that we also may study in phase IV studies if there's particular schedules that people want to look at. Yeah, I mean, Jeroen, I think these data certainly give KOLs and physicians in the community real options now to consider how they can treat patients to get them to complete response and so on and so forth. These data are really giving us some real options to consider. I mean, when you're talking about potentially exploring different dosing schedules, are you considering maintenance kind of dosing or at some point going to a Q3 months or maybe even going to a Q6 months? I think that they're all things that could be explored. I think we just have to get more data. Yeah. I mean, we'll have a better idea once we get the phase III data and get into the LTE. Again, I mean, the data that we have just on the 150 or 300 is extraordinary. I think it's just going to give people in the field a lot of optionality. Certainly, as we continue to explore the LTE and perhaps possibly phase IV studies, those are the kinds of things that we'll want to think about. Yeah. In the ongoing EMBARK- CSU1 and CSU2, those are enrolling, I think, on clinicaltrials.gov. I think it's got a target, so to speak, of ending the studies on June of 2027. I think we'll have a better understanding maybe not ending primary completions, but hitting the primary endpoint, the 52-week study, right? I think we'll have an update on probably enrollment sometime first half next year, I imagine. Yes, we would. In the studies, is there any sort of anaphylaxis monitoring that's going on, maybe at baseline to try to even identify any potential, I should say hypersensitivity, not anaphylaxis, to identify any baseline risk factors like underlying urticaria, underlying previous hives, things like that? No, the patients all have urticaria, so that's true. There's nothing special we're looking at at baseline in that regard. Okay. Okay. Got it. Let's move on to maybe just remind us in terms of the powering. Obviously, both of these studies are against placebo, and you need the big sample size for safety. You probably don't need it on each of them that much for the efficacy side. Is there any chance to even look to see whether you can hit stats in the Xolair prior exposed subset, even maybe if you pull them? Yeah. Yeah, actually, that's the reason for the size of the study is that we did set the study up both to show statistical significance in the overall population and to have an adequate safety database, and also to be able to look at the population that's Xolair refractory and experienced. Okay. And then let's actually talk next about PN and AD, right? Both of those phase IIs are expected second half next year. In PN, we already have some proof of concept from the previous phase I-B, where you showed very good data. I believe you're still enrolling. Can you maybe talk quickly about the remind us the trial design and what gives you comfort and confidence in PN? Yeah. So the trial design, it's a randomized placebo-controlled phase II study. We're looking at two different regimens of subcutaneous dosing versus placebo. It's 120 patients. We're looking at the typical endpoints for PN. We're looking at an endpoint of 12 weeks, but we're looking at the percentage of patients who have a four-point reduction in NRS. And we're also going to look at the investigator global assessment. And I think we get confidence from the data that we have from the phase I-B that this is certainly a very effective drug at reducing it. I mean, phase I-B had remarkable results for being a single dose. And the data look to compare very favorably with other drugs out there. And then we also had the anecdotal case in the original CIndU study. So there's quite a bit of evidence that this should be successful in PN. Yeah. Yeah. I think hitting on both, Jeroen, the itch, reducing the itch, and healing of those lesions, I think that gives us tremendous confidence going forward. I mean, when you look at the data for Dupi, right, it's essentially kind of becoming more and more of the standard of care over time. What has Dupi showed, and what gives you ultimately confidence it could be fairly competitive? Yeah. Dupi shows a reduction of itch in the majority of patients, and they show lesion healing in a lower percentage of patients. We think there's room to improve in both those areas. That's based on the mechanism that were are mast cells considered pathogenic in that indication? That's what we're going to find out. I certainly think mast cells are pathogenic in itch. Tibor, did you want to comment? I think there was some skepticism of that role until we showed our phase I-B data, where it really demonstrated that this interplay between mast cells and sensory neurons is really critical to the itch. Of course, that's driving that incredible itch is what drives the scratching and the lesions. Yeah, the remarkable results we saw with just a single dose really suggest these mast cells play a pretty critical role in that itch cycle. Okay. And then maybe moving to atopic dermatitis. You started 120 patients, phase II started in December of 2024. Data, again, is expected in the second half of next year as well. Can you maybe give us also a little bit of a sense? What's the role of mast cells in AD? I think it's similar. This non-histaminergic itch that's going on that drives some of the worst symptoms in atopic dermatitis is thought to be through this mast cell sensory neuron interplay. Mast cells obviously also contribute to inflammation through when they degranulate and call in other cells, other immune cells, and activate them. We know there's an increase in stem cell factor that also helps attract and activate mast cells. We think it has a multifactorial role, but our confidence really comes from what we've shown already and what we believe will be a strong impact on the itch in these patients. Okay. That is also testing two different regimens, right, versus placebo? Correct. Yes. The primary endpoint, just remind me, is it also 12 weeks, or is it 16 or 24? The primary endpoint in that study is 16 weeks. Okay. Excuse me. Bless you. I have a window open. I think that's what it is. Okay. Let's move to CDX-622 because you just showed the phase I data. This was in the phase I healthy volunteer, was in 56 patients. It was a SAD and a MAD. We saw so far the SAD data from part one showing an 18-day half-life. For the audience, this is a stem cell factor times TSLP bispecific that's currently in phase I. Maybe give us a little bit of a sense. At this point, you're going to be starting the subQ formulation in part three in the fourth quarter, and the MAD is ongoing. I think we might see the data shortly. Can you give us maybe a little bit of a sense? What do you think this would be the next stage for you? It sounds like you're going to go to mild to moderate asthma, but maybe talk about the profile. Yeah. Just as an introduction, the pipeline behind barzolvolimab is to take advantage of our appreciation of the role of mast cells in a lot of different diseases and appreciating that in many cases, mast cells will be a strong contributor, but there will be other pathways also driving the pathology. We thought a combination of taking out mast cells and inhibiting the alarmin TSLP, which is a huge driver of TH2 inflammation, would be optimal in many different settings, pulmonary indications, allergic indications, and even fibrotic situations. We built this bispecific, which, as people who develop bispecifics understand, there is a lot of liabilities with that. We were extremely pleased to see that the pharmacokinetics are much like a regular antibody, and we have had no immunogenicity to date. Those are big hurdles for bispecifics. Importantly, in healthy volunteers, we could measure tryptase reductions indicating that we are definitely hitting the mast cells. This is step one. We're excited. We're ongoing in the multiple ascending dose, which is going to look at higher exposures. We're also introducing the subQ formulation. We're expecting to continue to have great data out of those two studies while we get some proof of mechanism in an asthma population. The benefit of that study is really the well-understood effect of inhibiting TSLP based on the data that's been published with Tezspire. We will get mostly biomarker information in that study that really shows us that 622 is working on both ends, shutting down TSLP, inhibiting mast cells, and in particular, lung mast cells. That will set us up for a number of different indications. We're, as I mentioned, considering different pulmonary indications. We also think food allergy would be a really interesting direction for 622 should the data continue to support that. Other pulmonary indications could be, what is it, would be allergic asthma or? Certainly, severe asthma is a consideration. As I mentioned, there's always challenges in doing large clinical studies there. We do like COPD and watching closely the results that are coming out from there. We've considered chronic cough as an interesting option. There are some other fibrotic conditions. As we finish out these phase I studies, we will evaluate and perhaps design a phase II approach that's multi-pronged, and we'll be able to talk more specifically about that next year. Yeah. I mean, Jeroen, we're definitely thinking of 622 as another pipeline and a product type of drug. We want to do it right. We want to check all the boxes as we move along. We want evidence to show us the way. Looking forward to getting more and more data out of this program soon. Yeah. Maybe, Anthony, you have a lot of catalysts next year. Do you want to maybe take a moment to summarize them and then let me know? Yeah. I'll try to take them in some sort of order. Moving forward, we've indicated that we'll start the phase III study in both cold U and symptomatic dermographism by the end of this year. In the first quarter of 2026, we'll have the phase II cold U and SD OLE readout from that phase II. We've guided that we'll have CSU phase III accrual done by the summer. That is the two-year part that we were looking at. We also believe we'll have AD data in the second half of 2026, PN data in the second half of 2026, and the 622 MAD data also sometime in the second half of 2026, as well as thinking through what other indications or what we'd like to look at for barzol and setting up the future studies for 622. There's a lot of work to be done, as always, but this is why we do this. Yeah. In both studies, it sounds like both of Embark CSU studies are enrolling pretty much sort of unpaced. Yeah. We're very happy with the enrollment. Like I said, we guided to two years, and we started it in the summer of 2024. We expect them to be accrued by the summer of 2026. Yeah. Terrific. I think we're right at time. Tim, thanks so much for joining. We appreciate it. Thank you, Jeroen. Good seeing you as always. Talk to you soon. You.