Good afternoon, everyone. Thanks for joining us here on day two of the Leerink Partners Global Healthcare Conference. My name's Tom Smith. I'm one of the senior biotech analysts here at Leerink, and it's my pleasure to welcome our next company to the stage, Celldex Therapeutics, and represented today by President and CEO Anthony Marucci, CSO Tibor Keler, and CMO Diane Young. Thank you all for joining us. Looking forward to the discussion.
Yeah. Great to see you again, Tom. Always good to talk to you, so.
Likewise. Just add a little bit of the state. 2025, great year of execution, some very good data points. I think, you know, for investors, clearly a lot of focus around the phase III CSU readout that we're now expecting in Q4 of this year.
Mm-hmm.
Study enrolled rapidly, way ahead of schedule.
Yeah.
Over enrolled. Seems like there is. We interpret that as evidence of clinician demand for better urticaria therapeutics, also patient demand.
Mm-hmm
...for folks that are, you know, it's a population we think has been pretty underserved historically. Anthony, maybe you could kinda kick us off and level set us, you know, highlights from 2025.
Mm-hmm
What else we have to look forward to here in 2026?
Yeah. 2025 was, as you said, a year of execution. Finished up our CIndU studies, both, and our CSU studies. For CSU, we finished our 52-week therapeutic study where we dosed patients out to 52 weeks, and then followed that on with a 20-week follow-up period for those patients, and we presented our 76-week data. In both of those studies, the data was unprecedented, right? At 52 weeks, we had up to a 71% complete response rate. Followed those patients out for another 28 weeks, and at 76 weeks, with patients off drug, 41% of those patients still had a complete response. The same thing for the CIndU study. We did our 12- and 20-week studies, finished them up in 2025. We presented the 12-week data.
Again, really, excellent data there. Then starting future studies. We initiated the phase III study in SD and in ColdU at the end of December, and that led us into 2026. You pointed out that we started the year by announcing the phase III CSU studies accrued six months ahead of schedule. They were the largest studies ever conducted in CSU patients that were antihistamine refractory and biologically refractory patients. We accrued 1,939 patients, was 109 patients above the level that we set. We were in 500 sites. We were in 43 different countries, great execution by our ops team.
Great kudos to our partnerships with our CRO and Diane's clinical science team, but it was a collective effort. Tibor and the CMC team made sure that drug was available to all these places, on top of managing the CDMOs, to get through phase III and commercial development from manufacturing. A big lift, as you can imagine, for a company our size, but certainly one that we relished in the fact that we could do it. We did it in a speedy time limit. There was an unmet need here, too, around the excitement. Interestingly, we had a good mix of allergists and dermatologists on this study.
In the U.S., where we accrued 26% of the study in the U.S., 53% of those patients were put on by derms, something that surprised many investors, thinking that it would be more just allergists. Again, we're just very, very happy and satisfied by what we've seen so far, and we look forward to flipping the card in the fourth quarter.
That's great. Yeah, I wanna double-click on that data point because I know you guys very thoughtfully wanted to make sure there was a representative derm-
Mm-hmm
...presence in this study to be able to drive potentially, like, the broadest uptake of the product possible. I would be curious if we have feedback, I guess, from the dermatology community over what, you know, what drove them. I'm also surprised. Sounds like you were surprised as well that the majority of patients in the U.S. are coming from dermatology practices. We've historically thought of this as more of, like, an allergist driven-
Yeah. We just thought because of the severity of the patient population that we saw in the phase II study, where 70% of the patients were considered very severe, that you wouldn't see the uptake by the derms in phase III, but we were very happy to see it.
Yeah. One of the other design elements we always liked about the study is you're enrolling the biologic experienced patients. Do we have a sense for kind of how that card has flipped over, like a proportion or, you know, a certain proportion that we were targeting?
The only thing we know at this point is 75% of the study was antihistamine refractory, and the other 25% was biologically experienced or refractory. That's what we know at this point.
Great. Okay. Excellent. I wanna talk about the data that you just presented at EADV and, look, we've always thought of this as, you know, your high efficacy option, unprecedented complete response rates that you alluded to in your opening comments, Anthony. I thought what was really intriguing out of the EADV data was the durability of effect I felt like was on full showcase. Maybe you could just walk through sort of the highlights of that data set in CSU, and then we'll come back and maybe talk about the commercial implications of what you're seeing clinically.
Mm-hmm. Yeah. What we showed was a subset of the patients from the CSU phase II study, and we were really focusing on that durability of response off treatment. We had the patients who had well-controlled disease at 52 weeks and then saw what happened to them as they went out to 76 weeks. Again, you know, very, very high rate of maintaining complete response. Those that did relapse, relapsed with mild disease and you can. There's a. It's a beautiful figure, you know, kind of a heat map of response that's really hard to describe. But we were able to show this.
We looked at the PK, and we showed that we had this complete response that was persistent despite the fact that, you know, barzolvolimab levels were below the level where you would be expecting to have significant KIT suppression. Also we did see, you know, tryptase coming back to normal levels. Quad AI also picked that up as a poster to highlight in their press release, which was really nice.
This was looking at patients who achieved response, basically like well-controlled disease, about half of them were complete responders, like seven months removed from treatment.
Yes.
Yeah, we think of that as relatively unprecedented, but I wanna talk about kind of the clinical implications of this. Like, what do we think that this is truly disease modifying?
What our experts have said to us is it certainly raises the question of disease modification. There's not a standard definition in this disease. You know, we certainly have a much longer response than can be explained by pharmacokinetics alone. You know, it is longer than you would expect. There is spontaneous remission, but it's a much higher rate than you would expect from that. You know, there's something about it that is, you know, causing this prolonged response.
What's the potential, like biologic rationale for that? Is it that you are totally depleting, wiping out mast cells, and the mast cells that repopulate are a different phenotype lineage?
Yeah. Certainly we think the mechanism of action is what's at play here, the ability of barzolvolimab to really take out the effector cell in this disease and keep it out of the picture for a long period of time. When these slowly come back and do come back, we're not seeing the same level of disease in those patients. You know, we followed them out to 76 weeks. It's certainly likely that eventually more patients would see their disease return and you know, that's still a really unprecedented length of time for controlling disease without treatment.
Got it. Yeah. Fascinating. Sorry, Anthony.
Yeah. Again, it speaks to the severity of the disease. You know, what our health experts are telling us that the longer you have had the disease, right? If you're going out four, five, six years, the less likely you are to have any kind of spontaneous remission. Seven years on the mean of duration of disease. These weren't patients that were gonna, you know, remarkably remit quickly. And to see that kind of response post the data and post submission, it was just remarkable to us. It. We think it has a lot of implications going forward.
Could you talk about the potential commercial implications of a?
Yeah
... drug with that profile? I suppose one aspect is just like unprecedented efficacy also could introduce potential either intermittent dosing-
Mm-hmm
or a curative like effect that. How does one potentially price for something like that?
Well, that's a discussion we have to have when we talk to the payers when we get there, and we got plenty of consultants to help us out with that. I think that, you know, as we look through the datasets, there are a couple of things that jumped out at us. You know, as Diane said, we did have a more severe population. Originally, we were just looking at the UAS-seven scores. What we also saw is that we had a high rate of patients with severe angioedema on the study. When you put those two numbers together, it turned out to be a good third of the study, 36% of our phase II, whose patients had both severe UAS-7 CSU, and they had a mean score of 53 on their angioedema score.
If anybody who understands angioedema, a score of 19 is considered severe, and the mean on our phase II study was 53. With that, we saw, you know, remarkable control over AAS7, which is the angioedema score. We also saw that improvement in quality of life as well as the complete responses. When you take all three of those pieces of efficacy into consideration, there is a path for both frontline inclusion for those patients that have severe angioedema and severe CSU, and then the other entry point, which would be second line advanced label post a DUPIXENT or post a XOLAIR or remibrutinib going forward. Those are the two areas where we see an entry point, and something that I don't think a lot of investors were paying attention to.
Yeah. That's very interesting. Wanna talk about the EMBARK CSU study, and you've implemented a loading dose.
Mm-hmm
there. Obviously, you didn't have that in the phase II experience. Like talk about potential impact on both efficacy and safety with the loading dose.
Yeah. As you said, we're using the same dose as we had in the phase II, but we have added a loading dose to each one. A 300 milligram loading dose to the 150 Q4 week arm, and a 450 milligram loading dose to the 300 milligram every 8 week. We really did this on the basis of looking at the data from the study and modeling, and it looked like, you know, with the subcutaneous dosing in the study that we get a little bit faster response initially with the 300 milligram dose, but we also see that, you know, over the 8-week period of time, it starts to come back a bit.
With a loading dose, we can sort of smooth that out and hopefully get you know, more rapid efficacy up front. We don't think it's you know, we think it's gonna produce better you know, better efficacy, particularly early, and we don't think it's gonna cause any issues with the safety profile at all. You know, we have looked at that level of loading dose in our other phase II studies going on, and we have certainly looked at higher exposures than that when we were looking at intravenous dosing. We don't really see you know, a difference in terms of the safety profile.
That makes sense. Let's talk about expectations for the phase III and I guess how we're framing those. The phase II results, quite compelling. Obviously, replication of that would be, you know, the best.
Mind-blowing?
Yeah, the best pivotal results we've seen in urticaria.
Mm-hmm
The agents that are currently approved and that we have late-stage data for all look relatively similar, kind of in the XOLAIR range of
Mm-hmm
efficacy. Just sort of help us frame, like, how you think about good results. Is it just something kind of north of what we've seen from the XOLAIR? Is there a certain threshold that you're looking for?
I think our expectation is that we would have data similar to our phase II data. I mean, that's what we're hoping for, especially when you add in the loading dose, which, again, we're just trying to get a better effect early on. At the end of the day, whether you're getting the 150 or the 300, you're getting similar doses anyway, but it's just a matter of can you get those responses faster. So that's our expectation. But at the same time, you know, being a finance person, you're always modeling in, you know, improvement in the placebo rate, a decrease in your drug rate, and at the same time, we powered the study 90% to show a 10-point improvement. I mean, that's the hurdle. We think the study is very much well overpowered.
On top of that, we also are powered at 90% to show a 10-point improvement in the refractory population. I think, you know, if we can get anywhere near what we had in phase II, it's an absolute slam.
Yep. Just to build on that, but on the safety tolerability-
Mm-hmm
side. Similarly, replication of phase II, we would be very comfortable with that. Is there anything particularly?
Yeah
that we're looking for or anything that we're kind of managing around?
Well, Diane, go ahead.
No. I would say, you know, we're looking to, you know, see similar profile to what we saw in phase II.
Yeah. I mean, you know, we've already had 600-700 patients already in our various studies, so I think we're very comfortable with the safety profile. If we can match up safety profile in the phase III, that would be remarkable.
Yep.
'Cause remember, the neutropenia was all transient. The hair lightening and the hypopigmentation were all grade ones, very, very mild, and they do reverse, so that's our expectations going forward.
Right. Just remind us the long-term experience there. I think it was about three-quarters of patients stayed on drug, and of those, like three-quarters of patients complete responders. Is that right?
In terms of?
In terms of long-term CSU experience.
Yes
Yes. Yeah
over the course of a year.
Mm-hmm.
Yeah.
Yeah. Okay. That's great. Now let's talk about the market opportunity. It's fairly dynamic times. We have Rhapsido that was approved. remibrutinib seems to be launching well. I guess any early market feedback that you're hearing on that launch, and how does that launch shape the way you're thinking about kind of where barzolvolimab fits in?
Yeah. Again, like I said, where I think we fit in are two entry points, right? They're both areas where we think the data is superior, and that's in the severe angioedema patients and severe CSU. The other entry point is you don't do well or you're not completely controlled on XOLAIR or remi DUPIXENT. We would be the drug of choice in second line advanced therapeutics. That's the way we look at it. We feel that we have a clear space to operate, right? We're not competing with them. What we're hearing about the Rhapsido launch is that it's going well, that doctors seem to like it, and we expected that. It seems very XOLAIR-like in its efficacy, but it's an oral, so you gotta take it twice a day, every day.
If you miss doses here and there, you tend to have hives pretty immediately. Not unexpected, but evidently we think that's gone well, and I think longer term, that's good for us, right? It's been an underserved population. We know that there are plenty of CSU patients out there. We had so many companies targeting CSU as an indication with their drugs. There have been 28 companies that have targeted CSU as an indication for their drugs, and it's Sanofi and Novartis and Roche, Novartis with XOLAIR, and hopefully now us that have succeeded. Everybody else has not done well, and that includes companies that have billion-dollar drugs elsewhere.
Yep. I wanna talk about inducible urticaria, where we've launched the phase III.
Mm-hmm.
There's another one. We saw data at EAACI from the inducible urticaria experience. You had actually had a late-breaking poster at EAACI. Maybe just kinda hit the highlights on that data set, and then for the phase III CIndU experience, like, are there tangible learnings we can take away from the urticaria operational execution?
Mm-hmm
enrollment aspect that we can apply to CIndU?
Yeah. The data that we showed at EAACI, the late-breaking poster was retreatment data. In the CIndU phase II, they received 20-week placebo-controlled period, and then when they were in the follow-up, if they recurred in terms of symptoms, they could be retreated. What we showed in that poster was that as we really expected, when you retreat, you get the same response as you did initially. There was no diminution in the response, and the safety profile was very similar. We expected that, but it was just, you know, it was nice to see that. The other data that we presented was 20-week placebo-controlled data just showing improved quality of life and urticaria control.
In terms of, you know, what we've learned from the CSU study, I think we've learned a lot. We're actually going back to many of the sites that we used. It's a smaller study, so we don't need so many sites, but we're, you know, we're using the same CRO. We're going back to the same sites. I've gone to the investigator meetings, and the investigators are all very well trained in barzolvolimab, and so it's been, you know, it's really. This is a very easy study to get started.
Can you talk about the translatability of, I mean, the, you know, unprecedented efficacy, I would argue, in both CSU and CIndU , like, other considerations now as we move into large phase III cold urticaria and SD studies? The endpoints, I think, specifically in cold urticaria, have been a little tricky. Just maybe walk us through how you've designed and how you've kind of like optimized for success in those settings.
Yeah. We are using the same endpoints as we did in phase II in terms of the primary endpoint being complete response by provocation test. That's what we used in phase II. That's, you know, we've gotten alignment on that. We're also incorporating into some of our secondary endpoints, you know, some patient-reported outcome data, particularly looking at itch as well, which is something we learned from our, you know, our phase II study. You know, we've learned a lot from the phase II about how to use those provocation tests, how to instruct the sites and things like that that are useful in terms of the phase III.
I wanna switch gears from urticaria to. We have a couple other datasets coming this year. We'll start with prurigo nodularis, and it sounds like we may get that phase II proof of concept study first, potentially.
Mm-hmm.
You have phase I-B data.
Yep.
Really nice signal. That was with the IV form of the drug. I guess two things. Just, like, remind us, level set us on the rationale for depleting mast cells in PN and how that translates to clinical effect, and then when you think about translating the phase I-B to this phase II study, like, remind us of the differences besides just, you know, we're using the subQ now.
The rationale is really that there has to do with the mechanism of itch, and it's actually a you know growing area of research about the relationship between mast cells and sensory neurons and the involvement in diseases with itch, and prurigo nodularis is such a disease. We actually started our research because we saw a case of prurigo nodularis in our CIndU, our phase I-B CIndU study, and it completely responded, and that led us to do phase I-B in prurigo nodularis, which was a study that had single doses of barzolvolimab at three mg per kg and 1.5 mg per kg and placebo, and we treated moderate to severe prurigo nodularis patients.
Particularly at the three milligram per kg IV dose, single dose, we saw, you know, a 57% reduction, or 57% of patients had at least a four-point reduction in itch at the eight-week time period. We also saw healing of lesions, particularly again in the three milligram per kg group. The other thing in that study was we looked at tryptase, and we did see a difference in that indication between the three mg per kg and the 1.5 mg per kg in terms of level of tryptase suppression, which was different than what we had seen in urticaria. In setting up the phase II, we went to subcutaneous dosing, and we are looking at higher dose of barzolvolimab than we looked at in urticaria. Our highest dose. We have two doses.
One is 450 milligram loading dose with 300 mg every four weeks. We have 450 milligram loading dose with 150 mg every four weeks. It's, you know, two doses versus placebo. We've completed enrollment, and we're gonna have the data this summer.
Just to level set when data is coming out. The PN data will come out first in the summer, followed by the CSU phase III studies sometime in the fourth quarter, and then the AD data set from phase II towards the end of the year.
That's great.
That will be the order of when we're putting out data.
That's great. PN, just from a market opportunity perspective, I mean, this is one, I feel like investors, it's a smaller opportunity. The patient numbers are lighter than in many other dermatologic conditions. We do have NEMLUVIO that seems to be doing pretty well.
Mm-hmm.
DUPIXENT, it seems like also, you know, how do you think about, I guess, the potential commercial opportunity in PN?
Yeah, once again, I think it is a smaller indication. I would equate it to CIndU, which is around a third of the CSU population. Again, I think it's also underserved and underdiagnosed. I think as the NEMLUVIOs are out there, as the DUPIXENTS are out there, as we hopefully will get out there in PN, it'll be easier to find the patients, it'll be easier to treat the patients. Again, I think the market is bigger than what we're all thinking, right? There's very few markets that I've ever looked at that turned out to be smaller than we thought of, especially as we did more work. I think PN is another one of those disease indications that's underdiagnosed.
Yep. Last question on PN. How are you framing expectations for this phase II study?
Again, we'd love to mimic what we had in phase one. We're always looking to be at least as good as the current standard of care. Again, both NEMLUVIO and DUPIXENT got approved pretty much around the same time. What we think that if we have an effect on the NRS scores, which is the itch, and we also have an effect on the lesions in a bigger way, I think that's your differentiator.
Yep. Let's talk briefly about atopic dermatitis and, yeah, comes last this year, but a little bit different, I think, biologic rationale there. We don't know necessarily that AD is a mast cell-driven condition, but I guess like how are you guys thinking about like what's level of excitement around the AD readout? I guess level of conviction that we will see a signal there, and what does a good signal look like in this phase II study?
Yeah. I think AD was kind of an extension of the PN in terms of itch is still one of the predominant symptoms of AD. There do seem to be neuroimmune mechanisms involved in the itch. There's other roles that are hypothesized for mast cells in terms of the complex pathophysiology of AD. You know, I think we would say that, you know, with PN, we had. With the PN phase II, we had clinical data. We have, you know, responses in our hands. In AD, we don't have that level of certainty with that much data, but we, you know, we think it's a reasonable hypothesis to test.
Again, we say we would like to be, you know, as good or better than what exists. I think, you know, from a commercial standpoint, we would see this drug, you know, fitting in after, you know, the standard of care with DUPIXENT but before a JAK inhibitor. You know, that's the kind of position we're in.
Are we enrolling biologic-experienced patients?
We're enrolling it. It's an open, all-comer study.
All comer.
We're enrolling everybody.
Excellent. Okay. In the last minute, we're not gonna do this justice, but I wanna talk about CDX-622. You've generated some healthy volunteer data. We put it into proof of mechanism study in asthma. Just talk about biologic rationale for going there with TSLP stem cell factor, and what patients are we enrolling in this proof of mechanism.
Sure
When could we see data from this?
We're in phase I, both in healthy volunteers as well as in this proof of mechanism study. The concept with these more moderate asthma patients is to get PD data around both the impact of inhibiting TSLP as well as inhibiting mast cells. Because of the work that's been done with you know, approved TSLP inhibitors like TEZSPIRE, where there's a really clear biomarker pattern that we would expect to see. This is more validation work on this molecule for proof of concept. We think asthma is certainly an indication of interest as well as other pulmonary indications. It's a small open label study. We're not directing in terms of exactly when we would be presenting data.
We are presenting data in Q3 on the healthy volunteer study, which will include the multiple ascending dose as well as subcutaneous dosing.
Awesome. All right. Well, we'll stay tuned on that front. Big year ahead. Looking forward to all of the results this year, but especially the phase III CSU data.
Yeah. As we all are.
Thank you, Celldex team, for joining us. We'll stay tuned.
Thank you.
Thank you.