We're going to go ahead and get started. So welcome, everyone. Thank you for joining. I'm Gavin Clark-Gartner, one of the Senior Biotech Analysts here at Evercore ISI, and really happy to be joined by the Celldex Therapeutics team. We have Anthony Marucci, who is the CEO, and Tibor Keler, who is the CSO. Thanks for joining, guys.
Gavin, thank you for having us. Appreciate it.
Absolutely. All right, so why don't you just start off giving us a brief overview of Celldex, where things stand today, then we'll dive into specific questions.
Sure. So obviously, we're very happy about the fact that we're now a late-stage company. We began our phase III CSU study this past summer. We also completed our 12-week study in CIndU and are preparing in 2025 to go into phase III in that disease indication. And then behind the CSU and CIndU programs, we have a study going on in EoE, which we're expecting data in 2025. We initiated a PN study this year, as we also will be initiating our Atopic Dermatitis study this month. So as 2025 rolls around, we'll have two drugs in phase III, three indications in phase II. And then behind that, we've also begun our Healthy Volunteer studies with our first bispecific called CDX-622, which is a stem cell factor and TSLP bispecific. We're doing Healthy Volunteer studies now.
We expect data from those studies in the second half of the year and then look to do a phase I-B study in severe asthma as we think that that's the appropriate indication to have a proof of concept for that drug. So a lot of things going on. 2025 will include a lot of data and just moving straight ahead and very, very happy where we are.
Yeah, that's great. All right, so let's see how much we can dive into it. Probably have 45 minutes of questions to finish the 15. Starting off on the EoE side, commercially, what is the largest unmet need in the market with DUPIXENT approved today? Is it mostly around dysphagia? And do we know how many patients are suboptimally controlled on DUPIXENT?
We don't know how many are suboptimally controlled on DUPIXENT. We saw their phase III data. We certainly believe there's a lot of room for improvement there. And we think that this market is growing. Originally, looking at claims data, the numbers were smaller. But now, as we're doing real world work and as other people are doing real world work, we think that between the U.S. and Europe is about 455,000 patients that are post- biologically eligible. We think there's a lot of opportunity in this area. And certainly, we're looking to see if we can improve on the DUPIXENT data as well.
Yeah. All right, let's go over to the phase II trial design then. First, on the dosing side, you're using 300 mg every four weeks. I mean, what's the rationale for this dosing? Do you think a different dose is required versus CSU, or you just don't really want to miss on dose given the initial proof of concept study?
Yeah, I think it's the latter. So we haven't had experience in EoE and really wanted to make sure we had sufficient exposure. We do recognize that some indications may require higher doses. We think this is a very safe dose, and we expect this to give plenty of exposure to ensure that we don't miss on the efficacy side.
That's totally fair. And how do you manage the background medications for the phase II? If someone comes on topical steroids, for example, do they just stay on a stable dose?
So no, the topical steroids are not allowed. If it's the proton pump inhibitors or antihistamines and they're on a stable dose, those can be maintained. But the topical steroids is only potentially as a rescue medication.
That makes sense. And do you have any limit around prior DUPIXENT or other biologic exposure?
Just that they wash out. So prior biologics are allowed, but they need to wash out.
Yeah, we want to make sure that we get everybody we can so it's an all-comers study.
Got it. Have you set any expectations for the number of prior DUPI patients that may come in, or too early to say?
No expectations.
No, no expectations.
Got it. And are there any other patient selection considerations you would think about for this indication? Obviously, we'll have to see the data, but any kind of a priori assumptions heading in?
The eligibility criteria in this study are standard for EoE trials, just based on the histology and obviously dysphagia symptoms. We haven't limited any patient populations. We will, of course, subsequent to data, look to understand better whether there are correlations with certain endotypes of the disease. But currently, we're looking forward to getting the data in the full data set.
How do we think about the eosinophil count reduction side of things? I mean, I think you've noted you expect to see some reduction in eosinophils. How do we think about that magnitude?
It's a great question. So based on recent data with eosinophil targeting agents that haven't met the mark, we don't know that eosinophils are as critical to the disease as once thought or as indicated by the name. But we do expect, due to the strong interplay between mast cells and eosinophils, that if you take out the mast cells, you're likely to reduce the eosinophils. This study will tell us just how deep that reduction is and whether or not it meets the standards that the FDA has been looking for.
Yeah, got it. Do you have any data on eosinophil reductions from prior studies?
So we don't have any data from human studies looking at tissue eosinophil. But we have run a preclinical asthma model in which we did see a significant, about 50% reduction in tissue eosinophils in that study.
Okay, makes sense. Thinking about it from a regulatory perspective, if you guys hypothetically, let's say you have a large symptom benefit, right, but eosinophil reduction is on the weaker side, again, hypothetically, what does that mean from a regulatory point of view?
That means we'd have to come to alignment with the agency, which currently still looks for both endpoints to be met for regulatory approval. I think there has been some pressure about the validity of the eosinophil count per se. But of course, you'd need to demonstrate that these patients are truly having the kind of significant clinical symptom improvements to get movement on that. And so we'll cross that bridge when we come to it.
Yeah, we'll cross it pretty soon.
That's totally fair. That's fair. All right, so if we start to put pen to paper and kind of compare and contrast some data as we get closer to the second half of next year, is there any reason we can't kind of take the DUPIXENT phase III data set and start making some cross-trial comparisons?
Yeah, I definitely think you can do that. I mean, from our perspective, we're looking to be as good, if not better, than DUPIXENT, and their primary endpoints are our secondary endpoints in this study, so I definitely think you can do that.
Okay, that's clear. And you'll be laying out all this data. Will this be at a medical meeting also?
Medical meeting, yes. But again, we'll see when the medical meeting is. And if it's so far down the road from when we get the data, we'll put data out and then also present it at a medical meeting.
Okay.
Next steps for us would be moving forward and having another phase II meeting with the FDA.
Yeah, that makes sense. Other thing I was looking at was the comorbid atopic conditions that were in the DUPIXENT phase III. A lot of patients with rhinitis, food allergy, asthma, atopic derm. How do you think about effect size in those different populations? Could we see a larger effect size in some of them? And do they also inform some of your other ongoing studies?
They do. And I think all the studies that we've done have informed us as well. So you see some of those same comorbidities and not the same those indications that we're working on. And certainly, we can certainly work with them with barzol. But in certain indications like asthma, we think that it would be best for 622 because asthma is proven to have multiple pathways. And so we're very excited about being able to put 622 into the clinic and based on the Healthy Volunteer data, be able to go after it with two different pathways and see if we can have an effect there. But you can certainly do it with barzol. We just think that 622 would be a better way to go about it.
That makes sense. We'll come back to 622 in a second.
Sure. Just wanted to put that in there.
Yeah, great plug. Going over to Atopic Dermatitis for a second, I think one of my questions for this indication has always been patient selection. How do you think about that at the moment?
We're taking all comers, right? And fully understanding that most of the study will be DUPI failures or other IL-13 failures. We think that that will certainly happen. But we want to offer up to be an open all-comers study because you may get certain parts of the world where DUPI may not be approved or the other IL-13. So you may have that front line. But for the most part, we certainly think it's going to be those post-DUPI failures.
Yeah, and this question is probably early, and we'll talk about it maybe in another year or two. But just to throw out hypothetically, right? Are there any type of subgroups where you think there could be larger efficacy? Like, I'm just making this up, right? But maybe it's DUPIXENT failed, residual pruritus, elevated serum tryptase to some level. Any thoughts on how we appreciate because Atopic Derm is a large market, right?
It certainly is. And all of these diseases certainly seem to have different endotypes and patients that might respond better than other patients. And we'll certainly look at that. We know we have a strong effect, antipruritic effect. And so that makes sense clearly that patients are really suffering from that. But again, we're open-minded and want to look at the entire population.
And again, we'll look at some of the studies where there have been comorbidities and see if we can glean anything out of that. I mean, what's nice about these studies is that there are some comorbidities, and you can at least glean some real-world patient data as opposed to theories.
That's totally fair. On the prurigo nodularis side, anything to frame in terms of differences from the phase I-B? Anything to call out?
The phase I-B was a small IV administration study, which really gave us some very nice proof of concept data that we're building on. The larger placebo-controlled randomized phase II is looking at two different dose schedules given subcutaneously and including a loading dose. Yeah, otherwise, the patient population is similar to what we looked at before, just a much more robust study to look at that.
That makes sense. All right. And before we go to CSU and CIndU a little more on the commercial side, I did want to touch on 622 first or a little more on the clinical development side of things. As we're thinking about the initial phase I data that'll come out in all this , how should we think about the mast cell depletion and the serum tryptase in relation to barzol?
Yeah, so we've always said tryptase is an incredibly good marker for what's going on with mast cells. And we believe that that's not any different whether you're targeting the ligand stem cell factor or whether you're targeting KIT. So we will be looking very carefully at tryptase reductions. And our hope is to be able to see significant tryptase reductions through stem cell factor neutralization even in the Healthy Volunteers.
And how are you thinking about go-forward dose selection for this program? I mean, based on what you laid out, will you be using serum tryptase kind of in a similar way to barzol? Or is there anything else we can glean from the TSLP and target engagement side?
Yeah, I think we would like to have PD data for both targets. We don't expect much on the TSLP side in Healthy Volunteers. but we do, as Anthony mentioned, plan a proof-of-concept study to start rapidly in asthma patients where we have very defined PD biomarkers associated with TSLP neutralization. So we believe early in this program, we will be able to understand the dose-response with PD biomarkers for both sides of the molecule.
Got it and turning over to the safety side, any considerations? I mean, we're very familiar with KIT SCF, but as we throw TSLP into the mix with the bispecific, anything that we should think about differently?
Now, one of the reasons we chose this combination is the relatively very clean safety profile with TSLP targeting antibodies. We were very pleased with our non-human primate toxicology study that really had a no adverse effect level at the highest dose tested. So very clean toxicology program so far. So looking forward, our expectation is not to have different or new adverse effects.
Got it. All right, let's go to urticaria then and stay a little more on the commercial side here. What is your latest market research on in terms of the total market and the addressable market that you're pursuing? And specifically, I'm wondering if you guys are focusing more on the post-omalizumab population as opposed to the pre-omalizumab?
Yeah, so we've been on record to say that the population is at least 750,000. And I would imagine that the numbers are conservative, right? Especially with some of the work that Novartis has done in the CIndU side of things. And those numbers are coming up much higher than what others have done because let's face it, most of the work done in the past was based on claims data. And I think Novartis has done some real-world stuff. So I would imagine that the CSU market from a conservative perspective is still 750,000 patients, U.S. and E.U. Having said that, we think that the markets will grow. With so many people entering CSU, all of a sudden, it can't be a tiny little market. So I think people think that there is a lot of opportunity.
And as far as where we would fit in that paradigm, XOLAIR is a great drug. And we still think that it's been entrenched in the front line population. But as we have shown in our phase I-B and now in our phase II, we can work whether you're biologically naive, whether you're biologically experienced, or you're biologically refractory. And in the phase III, we're looking at all three patient populations. At the end of the day, that's the label we want.
And certainly, we think we'll slide behind XOLAIR. And then obviously, there's an opportunity with new docs coming on, whether the derms take on a more prominent role or whether primary care physicians start dosing patients. We're seeing nurse practitioners now. But the allergists are still the main primary drivers here in CSU. And I just think that it's another tool in their toolbox. And I think they'll take advantage of it. So we're really excited about the opportunity.
Yeah, great. And I was just looking at consensus models before this fireside. I'm seeing the price that's in there for barzol is $35,000-$40,000, give or take. And I guess I'll phrase the question this way: if I'm looking at some of the, and based on your comments, if you're maybe targeting more of the post-oma population commercially, not to say from a label and clinical perspective you're not going earlier. But if you're targeting more so the post-oma population commercially, I'm trying to think of analogs. I come up with Cibinqo for a JAK1 in the Atopic Derm space, launched at $70,000 at a premium. You have kind of RINVOQ around the $80,000 range. Why does barzol not shake out in that similar range? Why would it be in the $30,000-$40,000 range?
Yeah, I don't know when these guys put their models together, right? So it varies, right? So they know what XOLAIR is getting based on the label. But we also know that there are a good number of patients on XOLAIR that get updosed and whatever. And it can't be the same price as the label. We know DUPIXENT is in that $50,000 range. We think Galderma's drug in PN, I think it was at $58,000. So I think there's a lot of room for flexibility on the price. But certainly, the 76-week data that we're going to show for CSU will be critically important to that number because we're going to see how long patients kept their response post-being treated. And I think that that will be instrumental in talking to payers about a premium. So I think at some point in 2025, we'll certainly get a better number than 2035 or 2040.
That makes sense. That makes sense. When are you planning to share that 76-week data?
So we're probably targeting EAACI in 2025. I think that would be the appropriate time to do that.
Yeah, that makes sense, and do you have any ongoing market research projects, whether that's in terms of doing a detailed analysis, whether that's claims, et cetera? Do you have pricing projects?
Yeah, yeah. I mean, look, we need to do patient interviews and hear from patients. We're doing more questioning of docs. And again, when a doc says that their patients are doing great, we need to define that better. And as we are defining it, we're finding that they're not doing that great. Some patients are doing well, but certain patients are not doing well. So we have to reframe the questions and what constitutes good, what constitutes well control, what constitutes complete control. So that's work that we'll keep doing in 2025 because we want to get clarity around that.
Yeah. And that was one of the questions I had here, which is essentially how many patients today are two questions, really. How many patients today who are on XOLAIR are "suboptimal responders"? The question is kind of how you define that. And the other piece is how many patients are no longer on XOLAIR who have been non-responders.
Yeah. And again, the work we're doing here certainly is higher than what we started at. And we think it's upwards of 50%.
Yeah, that makes sense. Maybe I'll just ask one closing question. I mean, you framed a lot of the upcoming milestones for 2025. But I'll just ask bigger picture as you start to think about additional indications beyond the multiple ones you already have ongoing. What are some other areas that you think about?
So, depending on the EoE data, and we're hopeful that it's positive, that that would expand some additional GI indications. Certainly, we want to look at these comorbidities in the CSU and CIndU studies and see if there's a good pointing us towards some other indications because quite frankly, clinical data is a lot more valuable than a theory that clinicians come up with. So those are the kinds of things that we'll look to do. But we have five indications. And can we expand it to six, seven, and eight? Sure. But we want to do it in a prudent manner.
Yeah. Awesome. Really appreciate the time, Anthony and Tibor .
Thank you.
I'm sure we'll speak again soon.
Great. Thank you.