Celldex Therapeutics, Inc. (CLDX) Earnings Call Transcript & Summary

Okay. Well, welcome once again, everybody, to the 46th Annual TD Cowen Healthcare Conference. I'm Yaron Werber, 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. So team, thanks for joining. We appreciate it.

Thank you. Appreciate you having us.

Lots going on, lots of big announcements on finishing both enrollments in the CSU, the EMBARQ program and starting the Phase III CIndU study as well. So it's going to be an action-packed year for this year, plus prurigo nodularis data and AD data. So lots really going on.And 622 data, and we only have 28 minutes just to orient us. So maybe the faster than enrollment than expected enrollment for EMBARQ despite competition, what does that tell you? And kind of what are you seeing? Is the enrollment more U.S.-centric? Is it really global in nature?

No, it's global in nature. And certainly, we just think that there's an excitement around the drug. There's an excitement around the PIs that were on the study. And certainly, you had Remi getting approved this year in '25. You also had Dupi getting approved and then the face of that to accrue a study 6 months prior to your guidance. We over accrued the study because we had patients in screening when we announced that we were going to close. So it's just a tremendous amount of enthusiasm, we believe, for the drug, for how it went and for the future of it.

And then can you just remind us what you said on powering for the studies and your ability to then obviously combine them as well?

Yes. Well, so 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. But 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. So the overall group is overpowered in the sense.

And what about the powering for that subgroup.

90% to see a 10-point difference, yes.

Excellent. I mean a 10-point difference is very doable. I mean it's massively overpowered given the data. And it's at 52 weeks.

12 weeks -- sorry, 12 weeks is the endpoint. Yes.

12 weeks, but the study is 52 weeks...

The study is 52 weeks. We have a placebo-controlled period for 24 weeks and -- but the primary endpoint is at 12 weeks.

And when you're looking at both subtypes, subgroups, the naive and the experience, 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 are similar kinds of responses in both groups. This is obviously a much larger data set, but we expect to see similar results.

With -- as you kind of think about what the bar is, what your sense is the bar maybe even in the Oma experience?

I mean we're looking for statistically significant benefit. Our rates are higher than anybody else's. We're looking -- we're hoping for the same thing.

Yes. So 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 competitor drugs while the patients were on treatment. So as you remember, at 12 weeks, it was upwards of 51% at 52 weeks. It was deepening in upwards of 71%. So 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.

And I would just say for omalizumab refractory, there is nothing that's been approved or has demonstrated statistically significant efficacy in that population.

And what about -- can you just remind us what did Remi show in that population?

So Remi has not precisely looked at that population. They have done analyses where they've looked at omalizumab experience. They don't see a statistically significant difference that they've reported. They do see some -- it looks like they have some activity there, but they haven't -- it's not sized to look at that.

And what was the magnitude of the difference even not start saying?

They see kind of a difference similar to what they're seeing in their overall population.

Is the study powered to look at 2 different doses? You're doing 300 loading with 150 every 4 weeks and 450 loading and 300 every 8.

We didn't specifically power it to look at a difference in doses.

And so based on that, you decide which one dose or both to file?

Correct. Correct. And often, FDA will approve several -- a couple of doses because it's good to have options.

You noted the 76-week data. And at that point, patients were off therapy for about even as long as 27 months, right? And the mast cells repopulate by 28 by 2, 3 months completely?

So yes, based on our -- the tryptase levels coming back throughout this 7-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.

And so 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. And in these patients where you've really shut this down for a full year, I think there's a profound effect in terms of the timing that it requires for the disease. I mean, we do expect that in the 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. So we're still learning about exactly what's going on, but extremely pleased with this unprecedented activity.

With respect to what you might be able to include in section -- clinical Section 14 in the label with this long-term data, does it have any translatability? Or is it going to be mostly coming from the Phase III?

I mean, probably most of the data in the label will be from the Phase III. That's the precedent, and that's what we have to discuss with FDA, obviously.

We clearly have very strong publications that will outline this activity. I think that will help support it.

Support and that's something the [ MSLs ] and...

Absolutely...

But the thought is not to have a treatment-free period necessarily.

I don't know. In our initial label, I don't -- that will not be...

No, we want to give the docs that optionality.

Would you consider doing a Phase IV study with like, let's say, Q12-week dosing where you get to effect in 24 weeks, you go less durable?

You're asking me to spend more money Yaron. Yes. There are certain things that we would want to 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 want to look at, but I'm sure that's one of them.

What else would come to mind?

I think there's going to be all sorts of questions. And just to mention, we consider Phase IV type studies. There's also -- in this field, once something gets approved, the treating physicians themselves often use the drug in new ways and try to give it so that the patients will have the best experience.

Yes. Right, longer dosing period...

Longer dosing, double the dose, more frequent, less frequent.

Intermittent. Yes, 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 a reminder. Looking at Phase II data that we are seeing and the things [indiscernible] inclusion/exclusion criteria? Did the patient population -- 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. And it's obviously a broader geographic distribution, but we kept the criteria the same.

Just because you enrolled so fast, we've seen other companies that enroll really quickly and then they kind of get off kilter on the actual patients that got into the trial.

Tried to keep it exactly the same.

Yes, same patient population.

Since we're pretty close to commercial -- since we're closer to commercial than we were to actual data, any thoughts on pricing? Like are we thinking Xolair as a comp? Or is -- 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 Dupi, [indiscernible].

When -- in terms of some of the AEs and monitoring in the study for neutropenia, hair changes, it just standard when they come in and how frequently are patients coming in?

So in the study, patients are coming in on a monthly basis. And what was your initial question?

And then secondly, from -- once you're on the market, what are you anticipating in terms of monitoring? Is it just sort of baseline early on and then cadence of normal visits or anything particular comes to mind?

Yes. No. So we've been -- in terms of the question monitoring comes up most frequently with hematology. We've been very pleased with the consistency of the data across our study that 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. So it doesn't seem like monitoring would be beneficial in that situation.

And in terms of surveillance overall for hypersensitivity, how is that done in the study?

That's just adverse event reporting. You capture adverse events when the patients come in to visit the physician, you ask them if anything has happened and they report it.

Okay. 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.

And so that's this year?

We haven't guided on the exact timing.

We've said by the time the BLA -- Yes.

How is that study done? It's healthy volunteer and it's a short-term study...

Yes, we're giving healthy men clinically relevant dose of barzolvolimab, following them, obviously, understanding their impact, not just on their sperm count, but on other aspects of their sexual life of their hormone levels and all that's going to be captured and reported in. And 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 nonhuman primates, have you seen changes in hormone levels as well or just for [indiscernible]?

We actually did not do hormone level analysis in the preclinical study.

Okay. So as the market is getting more competitive, where do you think based on the data, barzol is going to get used? And is it slightly different initially, let's say, first year or 2 versus year 3 and 4?

Well, certainly, years 1 and 2 and 3 and 4 can be a little bit different. But we believe that there are 2 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. And we look at that from our Phase II studies where we looked at both severe CSU numbers severe angioedema numbers. And 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. So we looked at both the UAS7 of greater than or equal to 28 plus an angioedema score of greater than or equal to 50 and 36% of the patients on that study had both. So 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. And then the other entry point would be the drug of choice in second-line advanced therapy, right? So if you take Xolair or you take Dupi or you take Remi, once you go through those, whether you don't do well, whether you don't tolerate, whether you're not getting the control you're looking for, you drop down to barzol. So we think that, that is an excellent entry point on both. We certainly believe now that with [indiscernible] and Dupi on the market, it's going to certainly grow that market significantly. It's been an underdiagnosed market forever. And I think the analogs that I would leave investors with is go look at the psoriasis and the rheumatoid arthritis markets, whereas more competitors came in, the diagnoses became quicker. And then long term, you think that those second-line advanced therapy indications, that population becomes larger than the front line. So we think that it's got an excellent opportunity here.

And just remind us the loading dose is an IV loading dose and...

Everything subcu.

Subcu in the office?

Yes.

And then from that point in the study, it was health care or a caregiver administration?

Yes...

No, all of it's in office administration in the study.

And then would it be outpatient in the real world? So patients can self-inject at that point?

They can self-inject. We're looking -- we're going to start -- go commercial with a prefilled syringe in office. And the goal is within the first year to have a self-injected, auto-injector.

In the first year. Okay. But the prefilled syringe, they could still take at home as well.

They could.

No. Well, we won't -- we won't have -- you have to have all the instructions for the patients and things like that. And that's -- it's some additional work that we have to do to...

Before -- if the auto-injector isn't available you can still inject it...

Yes, that's correct.

Okay. And the auto-injector is about a year behind or so?

We would say so. We're doing the work on that now.

Any questions from the audience? Then maybe let's move to CIndU. So you presented the data at ACAI in '24, both in ColdU and SD. And now you're starting your Phase III, the EMBARQ-ColdU and SD study, 240 patients, 1:1 randomized. So 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 why choose that one and not the higher dose?

Yes. So both doses were active in the Phase II study, as you mentioned, 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. And we felt that 150, we had a lot of good data on. We do feel that the loading dose would augment the rapidity of the response at the beginning as we decided for CSU. So this is what we selected to go ahead with CIndU. I don't know -- did you have anything else?

No. I think this is a great compromise when you're doing a single-dose study. And I certainly expect that 150 monthly or 300 Q8 weeks is really a similar...

And you're using the higher loading dose here -- point, right, to get yourself a faster onset. The -- so Novartis recently assumed that the REM IND study showed stat significance against both and they're filing an IND. What -- how well diagnosed is CIndU relative to CSU? It's obviously about 15% of the overall market.

I think 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 if you have a ColdU and very severe reactions, that's probably easy to figure out. But some of these -- some of the other ones may be more challenging. So I think that CIndU is probably underrecognized, undertreated, et cetera, just like CSU.

Yes. And again, drugs coming on the market is only going to make that market more available to be diagnosed. And then certainly, if the drugs work, you'll see more people getting treated.

Yes. Maybe let's go back to CSU for a second and Dupi. How do you think Dupi is getting used just given the data? So the data on the oma experience wasn't good. So it really should be for Oma naive, but Oma is going biosimilar late this year.

I mean, I've heard that it's being used with comorbidities. So if you have AD and you have a concomitant CSU, it's being used there. But 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 seems to be the other group.

Not a great drug, but easy drug to give or drug they're comfortable with. Okay. Let's move to the PN study. And maybe just remind us the trial design and what you said on timing? And then maybe we'll talk about the Phase Ib data.

Yes. So the PN Phase II randomized placebo-controlled trial, we're looking at 2 doses of barzolvolimab versus placebo. We have 24-week placebo-controlled period, 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. So we're now in the process of cleaning the data and getting ready for data readout later this year.

So in the Phase Ib, this was 24 patients. It was only a single dose, right? Showed a clinically meaningful 4-point reduction in itch, 57% of patients on the lower dose and 43 -- actually, I'm sorry, at the higher dose and 43% at the 1.5 mg per kg lower dose achieved the endpoint at 8 weeks versus, I believe, 25% or so on placebo. There's also obviously good data on skin clearance and almost clear and clear versus essentially none on placebo. What's most important in PN? Is it skin clearance? Or is 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 getting a lot worse. But I think the lesions are also very disfiguring and very uncomfortable for patients. So I think what patients want is both. They want rapid relief of itch and they want clearing of the lesions.

And 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. If we have -- if we work on both ends, that's a win. .

And the 2 doses that you're using, is it the same 150 Q4 and 300 Q8?

No. In that study, we're -- our higher dose is 300 Q4, and then we're using 150 Q4. And the reason we went with a higher dose there was because in the Phase Ib, it looked like the 3 milligram per kilogram worked better and the tryptase suppression was more complete. And that was a little bit different than what we saw in our early studies with CSU. So we wanted to make sure we included a high enough dose to look at everything.

We want to make sure we don't underdose those 2.

And the loading dose is still 300 -- or is it 450 as well? It's 450. So everything -- because it's a much more -- right, it's a higher severity disease essentially where it needs higher suppression. And is it powered against placebo...

Yes, each arm versus placebo.

Each arm is about 45 patients or so.

It was -- well, it's -- we had 140 total patients, but we planned for 40. Yes.

Okay. So it is powered against placebo.

Yes.

Is the next step a Phase III? And is the primary at 12 weeks? Or is the primary longer?

We're going to follow what the others have done, whatever if it's 12 weeks, we'll do 12, if it's 16, we'll do 16. But we're going to follow the path that's already been provided for us. So whatever that is, it's probably a 12- or 16-week endpoint.

Yes. But we'll certainly let the data guide us as to what our best features to differentiate might be and have endpoints related to that.

Okay. And so you mentioned the data is this summer.

Yes.

Yes. So then the next program is the Phase II atopic dermatitis, and I think the data for that is late this year, right?

Correct. Cadence will be PN, the CSU Phase III and then AD later on.

So AD is going to be later on. And AD is also finished enrollment.

Yes.

Yes. But the data is going to be later in the year. So can you talk about the trial design there?

It's actually quite similar to the PN study. It's a 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 because that study we did similar to others, 16-week placebo-controlled period, 16-week active and then 16-week follow-up.

And that's also 120 or did it overenrolled...

It overenrolled. It was 131, I believe, the final number overenrolled a little bit.

And here, you're actually looking at itch and then secondary endpoint is skin clearance.

Yes, correct.

What -- and so where does -- where do you think this fits? Because the endpoint is a little different than, let's say, a JAK or a Dupi endpoint, which is primary is more skin clearance first.

No. So we chose -- the reason we chose the itch endpoint was because we -- that's what we felt most confident about based on the PN data. So we thought itch, we have a better idea. But we certainly included all the other ones as secondary endpoints. And again, going ahead with a future trial, we would look at all the data and decide what was the most relevant thing for the primary endpoint.

Yes. So you asked about where it would fit. So we -- it's an all-comer study. But 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.

Yes.

I mean the activity on itch can also be a differentiator. What percentage of patients have severe itch or moderate to severe itch?

Patients had to have -- they had to have an itch score of greater than or equal to 5 at entry. I don't -- we don't yet have the demographics for everybody enrolled.

Still blind. Yes, still blinded.

Okay. Okay. Well, lastly and very important is the stem cell factor TSLP bispecific. And your Phase Ia, you started in December of '24. You had positive SAD data showing about an 18-day half-life, no immunogenicity, fairly clean safety. That was a single IV dose, and now patients are enrolled in the MAD, right? So we're in Part 2 now. And I think data is in Q3.

That's correct. Yes. So 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. So we should have all that data when we report this summer.

And so the subcu, the Part 3 is also going to be the summer. It won't be Q4. So it sounds like it's going to be at the same time.

I believe so.

And that's going to be a SAD.

Correct.

And so the natural question is what's next for that program? Is that going to go into asthma? Is it going to go into AD?

So we have started a proof of mechanism study in asthma. So from healthy volunteers, I think we'll get a lot of data related to the safety profile and to tryptase reductions, which will inform us about mast cells. But 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 at the level of the lungs in terms of inflammation, in terms of mast cells and other really important inflammation markers. So that's happening now. That's going to 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 opportunity, I believe, for a drug that inhibits both TSLP and mast cells.

And the sputum sample, did deep lung sputum or just regular sputum...

Lung...

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. And that study just recently started. So it was probably too early to have data this year.

Well, we're not informing about what timing we'll have data, but it is an open-label study. So for us, 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.