Okay. Well, welcome, once again, everybody, to the 46th annual TD Cowen Healthcare Conference. I'm Yaron Werber, a biotech analyst here at TD Cowen, and it's a great pleasure to moderate the next fireside chat with Celldex. With us today, Anthony Marucci, President, CEO, and Co-founder, Tibor Keler, EVP, Co-founder, and CSO, and Diane Young, Senior Vice President and Chief Medical Officer. Team, thanks for joining. We appreciate it.
Thank you.
Thank you.
Appreciate you having us.
Lots going on.
Mm-hmm.
Lots of big announcements. I'm finishing both enrollments in the CSU, the EMBARQ program, and starting the phase III CIndU study as well.
Mm-hmm.
It's gonna be an action-packed year for you for this year, plus, well, prurigo nodularis data.
Mm-hmm
AD data.
Data.
Lots really going on.
CDX-622 data.
Six 622 data. We only have 28 minutes... just to orient us. Maybe the faster the enrollment than expected enrollment for EMBARQ, despite competition, what does that tell you? Kinda what are you seeing? Is the enrollment more US-centric? Is it really global in nature?
No, it's global in nature. Certainly we just think that there's an excitement around the drug. There's an excitement around the PIs that were on the study. Certainly, you had remi getting approved this year, in 2025. You also had Dupixent getting approved. Then the face of that, to accrue a study six months prior, to your guidance.
Yeah.
We over-accrued the study 'cause, you know, we had patients in screening when we announced that we were gonna close. It's just, you know, a tremendous amount of enthusiasm, we believe, for the drug, for how it went and for the future of it.
Can you just remind us what you said on powering for the studies and your ability to then obviously combine them as well?
Yeah. The studies are 90% powered to see a 10-point difference in the mean change from baseline in Urticaria Activity Score 7 compared with placebo. Very importantly, it's powered to see that in both in the overall subset and in the overall group, and then in the subset who are refractory to omalizumab. The overall group is overpowered in a sense.
What about the powering for that subgroup, the OMA-?
9, 90%.
It's 90% to see a 10-point difference.
Both. 90% both.
Yeah.
Excellent.
Yeah.
I mean, a 10-point difference is very doable. I mean, it's massively overpowered given the data.
Right.
It's at 52 weeks.
12 weeks.
No, 12 weeks.
12 weeks.
12 weeks. Sorry.
I'm sorry.
12 weeks is the endpoint, yes.
12 weeks. The study is 52 weeks.
The study is 52 weeks. We have a placebo control period for 24 weeks but the primary endpoint is at 12 weeks.
When you're looking at both subgroups, the naives and the experienced, are you expecting similar results in both based on the previous data?
Based on what we've seen previously in our other studies, it looks like there's similar, you know, similar kinds of responses in both groups. This is obviously a much larger data set, but, you know, we expect to see similar results.
With as you kinda think about what the bar is, what's your sense is the bar maybe even in the OMA experienced?
I mean, we're looking for, you know, we're looking for statistically significant benefit. You know, you know, our rates are higher than anybody else's. We're looking... we're hoping for the same thing in phase III...
Yeah
I would say.
The interesting part coming out of the phase II study, Yaron, was that our 76 week follow-up data, the complete response rate there was 41%, and that was higher than any of the competitive drugs while the patients were on treatment. As you remember, at 12 weeks, it was upwards of 51%. At 52 weeks, it was deepening and upwards to 71%. You know, we really appreciate the fact that this drug works very, very well, works very, very rapid, and the deepening of response is also something that we're truly glad about.
I would just say for omalizumab refractory that, you know, there is nothing that's been approved or has demonstrated, you know, statistically significant efficacy in that population.
Yeah.
What about the, can you just remind us what did remy show in that population?
Remy has not precisely looked at that population. They have done analyses where they've looked at omalizumab experienced. They don't see a statistically significant difference that they've reported. You know, they do see some, you know, it looks like they have, you know, some activity there, but, you know, they haven't. It's not sized to look at that.
What was the magnitude of the difference even outside setting?
They, you know, they see, you know, kind of a difference, you know, similar to what they're seeing in their overall population. Yeah.
Is the study powered to look at two different doses? You're doing, you know, a 300 loading with 150 every four weeks and 450 loading and 300 every eight.
We didn't specifically power it to look at a difference in doses.
based on that, you decide which 1 dose or both to file?
Correct. Correct. Often, you know, FDA will approve, you know, a couple of doses because it's good to have options.
The, you noted the 76-week data, and at that point, patients were off therapy for about even as long as-
28 weeks. Yeah
... you know, 20 to seven months, right? The mast cells repopulate by two, three months completely?
Yeah, based on the tryptase levels coming back, you know, throughout this seven-month period, we know that they're at normal tryptase levels, which indicate that patients' mast cells are back to the same level as you would see in healthy patients or healthy individuals.
What confers that activity in your view, the durable activity?
Well, I think you have this profound impact on the effector cell that's driving the disease. In these patients where you've really shut this down for a full year, I think there is a, there's a profound effect in terms of the timing that it requires for the disease. I mean, we do expect that in a majority of patients the disease is likely to come back, but it comes back very slowly because you are repopulating these mast cells slowly. They may not be as sensitive to the triggers as they were when the disease was flaring for them initially. We're still learning about exactly what's going on, but, you know, extremely pleased with this, you know, unprecedented activity.
With respect to what you might be able to include in the clinical section 14 in the label with this long-term data, does it have any translatability or is it gonna be mostly coming from the phase III?
I mean, probably most of the data in the label will be from the phase III. You know, that's the precedent and that's what we have to discuss with FDA, obviously.
We'll clearly have very strong publications that will outline this activity, I think that will help support.
That's something the MSLs.
The use. Yes.
medical affairs can discuss.
Absolutely. Yes.
Right. The thought is not to have a treatment-free period necessarily.
I don't know. In our initial label, I don't-
No.
You know, that will not be in there.
Yeah.
No, we wanna give the docs that optionality.
Would you consider doing a phase IV study with like, let's say, Q 12-week dosing where you get to effect and at 24 weeks you go less durable?
You're asking me to spend more money, Yaron. Yeah. We There are certain things that we would wanna do in phase IV. That's certainly one of the options that we would have. I'm sure Diane and her team can come up with other things that they'd wanna look at, but I'm sure that's one of them.
What else would come to mind?
Oh, I think there's going to be all sorts of, you know, all sorts of questions. Just to mention, you know, we consider phase IV type studies. There's also, in this field, once something gets approved, the treating physicians themselves, you know, often use the drug in new ways and try to, you know, give it so that the patients will have the best experience.
Yeah. Right, longer dosing periods.
Yeah, longer dosing.
Intervals.
Double the dose. You know, more frequent, less frequent.
Intermittent. Yeah, those types of things.
Okay. Any questions from the audience? If anybody has any questions at any point, just go ahead and raise your hand and happy to take it.
Just as a reminder.
Go ahead.
Looking at the phase II data that we've seen and the phase III enrollments. Did you. I can't remember exactly what changed on inclusion, exclusion criteria. Do the patient population-
Yeah.
Was the patient population pretty fast or pretty similar or not?
Patient population exclusion, inclusion, exclusion was the same. The only thing we changed is that we did a loading dose.
Correct. It's obviously a broader geographic distribution. We kept the criteria the same.
Just 'cause you enrolled so fast, we've seen other companies that enroll really quickly, and then they kinda get off kilter on the actual patients that got into the trial.
Nope. Same.
We tried to keep it exactly the same.
Yep, same patient population.
Since we're closer to commercial than we were to actual data, any thoughts on pricing? Like, are we thinking Xolair as a comp, you know, how are we thinking of pricing now?
We're doing that work now. Certainly we have a ways to go before we can declare what we think it is, but we certainly are looking at a premium, to where Dupixent, Olumiant, and Rinvoq are.
When, in terms of some of the AEs and monitoring in the study for neutropenia, hair changes, is it just standard when they come in and how frequently are patients coming in?
In the study, patients are coming in, on a monthly basis. What was your initial question?
Secondly, from, you know, once you're on the market, what are you anticipating in terms of monitoring? Is it just sort of baseline early on and then, and cadence of normal visits or anything particular comes to mind?
No. We've been, you know, in terms of the question monitoring comes up, you know, most frequently with hematology. We've been, you know, very pleased with the consistency of the data across our study that, you know, we have neutropenia events. They're mostly mild. They reverse while the patients are on therapy, and we haven't seen any association with infections. It doesn't, you know, it doesn't seem like monitoring would be beneficial in that, in that situation.
In terms of surveillance overall for hypersensitivity, how is that done in the study?
That's just adverse event reporting. You know, you capture adverse events when the patients, you know, come in to visit the physician. He, you know, asks them if anything's happened, they report it.
Any update on the sperm study in men?
It's ongoing. We expect the study to read out in time for our filing for the BLA. That's the requirement.
That's this year?
We haven't guided on the exact timing.
We've said by the time the BLA is available. Yeah.
How is that study done? It's healthy volunteer.
Yeah.
It's a short-term study or?
Yes. We're giving healthy men, clinically relevant dose of barzolvolimab, following them, you know, obviously understanding their impact, not just on their sperm count, but on other aspects of their sexual life, of their hormone levels. All that's going to be captured and reported in. You know, just to remind folks that this is a known impact based on KIT biology that systemic inhibition of KIT will impact the maturation of sperm. It's 100% reversible. We've demonstrated this in our prior preclinical studies and certainly expect to see the same with our studies in men.
In non-human primates, have you seen changes in hormone levels as well, or just sperm maturation?
We actually did not do hormone level analysis in the preclinical study.
Okay. As the market's getting more competitive, where do you think, based on the data, barzolvolimab is gonna get used? Is it slightly different initially, let's say, first year or two versus year three and four?
Certainly years one and two, and three and four can be a little bit different. We believe that there are two entry points for us coming into the market. The first entry point would be frontline, first line advanced therapy in those patients that have severe CSU and severe angioedema. We look at that from our phase II studies where we looked at both severe CSU numbers, severe angioedema numbers. The way we measured severe angioedema, as you know, Yaron, anything above a 19 is considered severe. We went and looked at the median numbers in our study, and the median numbers were 53.
Wow.
We looked at both the UAS7 of greater than or equal to 28, plus an angioedema score greater than or equal to 50, and 36% of the patients on that study had both. If you want to look at it commercially and say, "Okay, I'm going to cut this number in half," we have a good entry point into that frontline therapy using those. The other entry point would be the drug of choice in second line advanced therapy, right? If you take Xolair or you take Dupixent or you take remi, once you go through those, whether you don't do well, whether you don't tolerate it, whether you're not getting the control you're looking for, you drop down to barzolvolimab. We think that that is an excellent entry point on both.
We certainly believe now that with Repzido and Dupixent on the market, it's gonna certainly grow that market significantly. It's been an underdiagnosed market forever.
Mm-hmm.
I think the analogs that I would leave investors with is go look at the psoriasis and the rheumatoid arthritis markets, where as more competitors came in, the diagnoses became quicker. Long term, you'd think that the second line advanced therapy indications that population becomes larger than the frontline. We think that it's got an excellent opportunity here.
Just remind us, the loading dose is an IV loading dose?
No.
No.
Everything's sub-Q.
It's sub-Q in the office?
Yes.
Yes.
From that point in the study, it was healthcare or a caregiver administration?
Yes. No, all of it's in office.
It's all in the study.
... in the administration in the study.
Yeah.
Would it be outpatient in the real world?
Mm-hmm.
Patients can self-inject at that point?
They can self-inject. We're gonna go commercial with a pre-filled syringe in office, and the goal is within the first year to have a self-injected auto-injector.
In the first year?
Mm-hmm.
Okay. the pre-filled syringe they could still take at home as well?
They could.
No. No. We won't have. You know, you have to have all the instructions for the patients and things like that.
Right.
... that's, it's some additional work that we have to do to, you know.
Right. The question is-
... be able to get that.
If the auto-injector isn't available.
Oh, okay.
you can still inject it.
Yeah.
Yes.
Okay. No, that's.
Yeah.
Yeah, that's correct.
Okay. The auto-injector's about a year behind or so?
We would say so.
Okay.
We're doing the work on that now.
Any questions from the audience? Maybe let's move to CIndU. You presented the data at AAAAI in 2024, both in ColdU and in SD, and now you're starting your phase III, the EMBARQ-ColdU and SD study. 240 patients, one-to-one randomized. Here you're doing a 450 loading dose and 150 Q4 weeks, right, against placebo. In the phase III, sort of the 300 was a little bit better in ColdU and 150 was a little bit better in SD. Maybe help us understand, you know, why choose that one and not the higher dose?
Yeah. Both doses were active in the phase II study, as you mentioned. You know, both of them were statistically significant in both forms of CIndU. When we came to design this study, because CIndU is a rare population than CSU, we wanted to just look at one dose to try and keep the study accrual times manageable. You know.
We felt that, you know, 150 we had a lot of, you know, good data on. We do feel that the loading dose would, you know, would augment the rapidity of the response at the beginning as we decided for CSU. This is what we selected to go ahead with CIndU. Did you have anything else?
No. I think, you know, this was a great compromise when you're doing a single dose study. I certainly expect that 150 monthly or 300 Q eight weeks is really a similar-.
Yeah.
Right.
You're using the higher loading dose here.
Yes.
Yes.
-to get yourself to your point, right? To get yourself a faster onset. You know, so, you know, Novartis recently assumed that the REM IND study showed stat significance against both and they're filing an IND. How well diagnosed is CIndU relative to CSU? It's obviously about 15% of the overall market.
I think, you know, there's actually been less work done on CIndU, and now that's starting to change. But I think CIndU faces all the same problems as CSU. I mean, I think there are some patients where they might have a very clear association, like, you know, if you have a ColdU and very severe reactions, that's probably easy to figure out. But some of these, you know, some of the other ones may be more challenging. I think this, you know, CIndU is probably, you know, under-recognized, under-treated.
Yeah.
et cetera, just like CSU.
Yeah. Again, two drugs coming on the market, it's only gonna make that market more available to be diagnosed.
Mm-hmm.
Certainly, if the drugs work, you'll see more people getting treated.
Yeah. Maybe let's go back to CSU for a second and Dupi. How do you think Dupi is getting used just given the data? The data in the OMA experience wasn't good. It really should be for OMA naive, but OMA's going biosimilar late this year.
I mean, I've heard that it's being used with comorbidity. If you have AD and you have a concomitant CSU, it's being used there. We don't have all the information that you probably would want.
We also hear that dermatologists may be trying it because they're so familiar with it, so that's seems to be the other group that's using it.
Not a great drug, but easy drug to give or drug they're comfortable with.
Yeah.
Okay. Let's move to the PN study. Maybe just remind us the trial design and what you said on timing, and then maybe we'll talk about the phase I-B data.
The PN phase II randomized placebo-controlled trial, we're looking at two doses of barzolvolimab versus placebo. We have, you know, a 24-week placebo control period, a 12-week primary endpoint. We're looking at patients with moderate to severe prurigo nodularis. The enrollment is completed. The planned number of patients was 120, and we had 140. You know, we're now in the process of, you know, cleaning the data and getting ready for data readout later this year.
In the phase I-B, now this was 24 patients, it was only a single dose, right?
Right.
Showed a clinically meaningful four-point reduction in itch. 57% of patients on the lower dose. Actually, I'm sorry, at the higher dose, and 43% at the 1.5 mgs per kg lower dose, achieved the endpoint at eight weeks versus, I believe 25% or so on placebo. There was also obviously good data on skin clearance on almost clear and clear versus essentially none on placebo. What's most important in PN? Is it skin clearance or is it itch?
I think they're both important. It's I mean, PN is one of the most pruritic diseases that there is, and the itching actually, the chronic itch contributes to the lesions, you know, getting a lot worse. I think the lesions are also very disfiguring and very uncomfortable for patients. I think what patients want is both. Like what they want rapid relief of itch, and they want, you know, clearing of the lesions.
That's our differentiation. If we have an effect on both, and I think we've shown that we do, small patient population, but we'll see it in phase II.
Yeah.
If we work, on both ends, that's a win.
The two doses that you're using, is it the same 150 Q4 and 300 Q8?
No. In that, in that study, we're our higher dose is 300 Q4, then we're using 150 Q4. The reason we went with a higher dose there was because in the phase I-B, it looked like the 3 mg per kg worked better and the tryptase suppression was more complete. That was a little bit different than what we saw in our early studies with CSU. We wanted to make sure we included a high enough dose.
We wanna.
look at efficacy.
Right. We wanna make sure we don't underdose the phase II.
Yeah. The loading dose is still 300 or is it 450 as well?
450.
It's 450.
450. 'Cause it's a much more, right, it's a higher severity disease essentially.
Correct.
It needs higher suppression. Is it powered against placebo even?
Yes. Yeah. The each arm, you know, versus placebo.
Each arm is about 45 patients or so?
It was... Oh, well, we had 140 total patients.
Yeah.
We planned for 40.
Yeah.
Yeah.
Okay.
Yeah.
against placebo.
Yes.
Is the next step a phase III? Is the primary.
Yeah.
at 12 weeks or is the primary longer?
We're gonna follow what the others have done. Whatever... If it's 12 weeks, we'll do 12. If it's 16, we'll do 16.
Yeah.
You know, we're gonna follow the path that's already been provided for us. Whatever that is, it's probably a 12 or a 16-week endpoint.
Yeah, we'll, you know, we'll certainly let the data guide us as to what our best features to differentiate might be and, you know, have endpoints related to that.
Okay. You mentioned the date is this summer?
Yes.
Yeah. The next program is the phase II atopic dermatitis, and I think the data for that is late this year, right?
Correct.
Um-
The cadence will be PN, the CSU, phase III, and then AD later on.
AD is gonna be later on. AD is also finished enrollment.
Yes.
Yes.
Yeah. The data's gonna be later in the year. Can you talk about the trial design there?
Sure.
It's actually quite similar to the PN study. It's a, you know, randomized placebo-controlled study looking at the same doses of barzolvolimab as we looked in the PN versus placebo. The endpoint there is the primary endpoint is the percent decrease in the peak pruritus score at 16 weeks. 'Cause that study we did similar to others, 16-week placebo control period, 16-week active, and then 16-week follow-up.
That's also 120, or it over-enrolled.
It over-enrolled. It was 131, I believe, the final number. It over-enrolled a little bit.
Okay. Here you're actually looking at itch, and then secondary endpoint is skin clearance?
Yes, correct.
Where do you think this fits? 'Cause the endpoint's a little different than, let's say, a JAK or a DUPY endpoint, which is primary is more skin clearance first.
The reason we chose the itch endpoint was because we felt most confident about based on the PN data. We thought itch we have a better, you know, we have a better idea. We certainly included all the other ones as secondary endpoints. Again, you know, going ahead with a future trial, we would look at all the data and, you know, decide what was the most relevant thing for the, you know, for the primary endpoint.
Yeah. You asked about where it would fit.
Mm-hmm.
You know, It's an all-comer study.
Mm-hmm.
Where we think we would fit would be the IL-4, IL-13 failures, but before you get to the JAKs.
Before you get to the JAKs.
Yep.
I mean, the activity on itch can also be a differentiator.
Mm-hmm.
What % of patients have severe itch or moderate to severe itch?
They had to have an itch score of greater than or equal to 5 at entry. We don't yet have the demographics for everybody enrolled yet.
Yeah, still blinded.
lastly, excuse me, and very important is the stem cell factor TSLP bispecific. You have phase I-A, you started in December of 2024. You had positive SAD data showing about a 18-day half-life, no immunogenicity, fairly clean safety. That was a single IV dose, now patients are enrolled in the MAD, right? We're in Part 2 now, I think data is in Q3.
That's correct. Yeah. We will be reporting both on the multiple ascending dose with the IV dosing, but also we are doing a single ascending dose with our subcutaneous formulation, which we've introduced into that trial. We should have all that data when we report this summer.
The, the sub-Q, the phase III is also gonna be this summer?
Yes.
It won't be a Q4? It sounds like it's gonna be at the same time.
I believe so.
that's gonna be a SAD?
Correct.
The natural question is what's next for that program? Is that gonna go into asthma? Is that gonna go into AD?
We have started a proof of mechanism study in asthma. From healthy volunteers, you know, I think we'll get a lot of data related to the safety profile and to, you know, tryptase reductions, which will inform us about mast cells. We really want to be, understand what we're doing in patients. Asthma made the most sense because we will get a lot of PD data related to the TSLP side of the molecule, but also we're collecting sputum samples. We'll really get, information on what we're doing, you know, at the level of the lungs in terms of inflammation, in terms of mast cells, and other, really important, inflammation markers. That's happening now. That's gonna help inform the broader program. We certainly think pulmonary indications make a lot of sense for this combination.
We're also looking at potentially things like food allergy and a lot of, a lot of opportunity, I believe, for a drug that inhibits both TSLP and mast cells.
The sputum sample, it's deep lung sputum or just regular sputum?
Lung. Lung, yeah.
Lung sputum.
Yes.
With a bronch or with a swab?
I think this is induced sputum where they essentially are induced to bring up sputum from the lungs.
Okay. That study just recently started.
That's correct.
Right? It's probably too early to have data this year.
We're not informing about what timing we'll have data, but it is an open-labeled study. For us, you know, we hope to be getting data throughout the year in terms of how that's going and helping us inform moving forward.
Well, terrific. Team, thanks so much for joining. We appreciate it.
Thank you.
Thank you.
An exciting year.
Good to see you.
We'll follow closely.
We look forward to it.
Thank you.
Thank you.
Thank you.