Could be pool. [audio distortion]
All right. Seems like we're live.
We're live, man.
Thanks for joining, everyone. Next up, we have the team from Celldex Therapeutics. We have Anthony Marucci, Diane Young, and Tibor Keler. Thanks so much for joining. I'm going to kick it over to you guys just for an overview of the company, where things stand today, and then we'll go into Q&A from there.
Okay. So we finished off 2025 as a late-stage company in phase III development in our CSU program, and we're looking to initiate a phase III in our CIndU program by the end of this month. On top of the CSU, cold and SD, we also have a phase II study going on in prurigo nodularis, which is expected to read out in 2026, and atopic dermatitis in a phase II that's also supposed to be reading out in 2026. 2026 is going to be a huge year for us. We expect our phase III study to complete accrual in the CSU study. We've always guided to two years of accrual when we started the study in July of 2024. So we think by July of 2026, we'll complete accrual and then look to flip the card at that point.
Beyond Barzol, we have our second program that's currently in healthy volunteer studies called CDX-622. It's our first bispecific program, which targets stem cell factor and TSLP. We have it in three healthy volunteer studies. We just finished the single ascending dose, or the SAD study, as they call it. On the scientific terms, we're accruing the MAD study now. Then we're also going to be doing a subQ single ascending dose study, which will read out in 2026. And then we will start a proof of mechanism study in severe asthma. So lots of stuff going on. The company's growing, and we look forward to 2026.
Awesome. All right. Maybe we can flip the order here. Let's actually start out with 622, and we'll come back to Barzol. Maybe we could just kind of walk through kind of one of the key pitches on SCF-248 versus SCF-220, and I'll phrase the question this way. With Barzol, and this is specifically talking about the SCF side, kind of isolating the TSLP for now, but on the SCF side, with Barzol, we've seen that you need more than 50% tryptase reduction to get full efficacy. What you've achieved so far is about 50% with the highest doses that you've gone to. Why is that enough?
Yeah. So let me start by introducing it a little bit in the context of so stem cell factor is the sole ligand for KIT. In theory, inhibiting stem cell factor should result similarly as inhibiting KIT. The nuance here is that there are two forms of stem cell factor, a predominantly membrane expressed form called SCF-220 and a predominantly secreted form that ends up as soluble SCF, which is called SCF-248. Our bispecific CDX-622 has an SCF neutralizing antibody that's really predominantly targeting the soluble form, or SCF-248. We believe that there's a real opportunity here in that mast cells, we feel, and particularly in the context of inflammation, rely predominantly on the soluble form of stem cell factor, whereas many of the other KIT-related functions, such as hematopoiesis, melanogenesis, et cetera, are more reliant on the membrane form of SCF.
So now getting to your question, yes, there is a potential trade-off that one may not be quite as omnipotent against all mast cells by targeting only the soluble form. On the other hand, what we've seen so far and what we've presented regarding the toxicology data, we do think that by targeting stem cell factor, the soluble form of stem cell factor, we may avoid some of the KIT-related adverse effects targeting other KIT functions. What we don't know yet, so we've presented at least with the single ascending dose that the maximum inhibition was 50%. So first of all, we're looking forward to the multiple ascending dose, which is greater exposure, and we may certainly drive tryptase reduction further. Secondly, what we don't know is whether that 50% reduction is inhibiting your mast cells 50% in all tissues, or are we really targeting some mast cell population?
For example, mucosal mast cells may be far more sensitive than, for example, dermal mast cells, and that's something that we're learning right now. So tryptase is a nice biomarker. It's great to follow, but we have more to learn. And we're really excited about the data. And we really look at this not just in the context of mast cell inhibition. We are also super excited about what we're learning about TSLP and TSLP inhibition in a lot of different indications. And we think the combination is largely non-redundant and will have a lot of opportunity in different indications.
Awesome. I'm trying to think through some of the ways to prove out that thesis before actually testing directly in patients on the SCF side. Are you taking skin punch biopsies in this study at all?
We do have some skin punch biopsies being performed, so we'll be getting that data later together with the multiple ascending dose. And we're also introducing the subcutaneous dosing. So that's data that we'll be presenting next year. We're also looking at this in preclinical models, and we think that that's going to be valuable to really understanding which mast cell populations are most impacted.
I'm trying to think through how to interpret the skin punch biopsy data. The first thing that came to my mind is, all right, we would look for in the skin punch biopsies, look for the same amount of inhibition as like 80% or 90%, kind of what Barzol did, but with a 50% tryptase reduction, whereas Barzol was at 80% or 90%. Hopefully, that made sense. But is that the right way to kind of interpret this? Do we have clear benchmarks to do that?
Yeah. I think it's a little bit more complicated than that. It depends on what technology you're using to measure the mast cells. Obviously, we have a number of different ways by immunohistochemistry looking at RNA, so understanding what their gene expression profiles are. We're doing a combination of those things. And again, each indication, I think each situation will maybe have its own perspective in terms of what level of inhibition or depletion is associated with the best clinical activity. We have that data, of course, with Barzol for CSU and urticaria, which is great.
Awesome. That makes sense. What about any biomarkers on the TSLP side of things?
Yes. Not much in the healthy volunteer study, but that's really the rationale for our going into a small asthma study. It is a biomarker study, and the concept there is that we understand very well, primarily from the TEZSPIRE data, what inhibition of TSLP does in those patients in relation to different biomarkers. And we will also be looking at, of course, our impact on lung mast cells and other inflammation signals. So we will have that data, certainly with that study.
Awesome. And just back to the SCF side, I know AbbVie had this program they licensed, I think, from Opsidio. It's an SCF-248. After a phase II atopic derm study, I have not heard anything about it for a long time. What do we know about that?
We're in the same boat. So we saw the press release. We understand that they went into an atopic dermatitis study that was funded by AbbVie. We're aware that that's no longer continuing, but there's been nothing publicly released about that.
Got it. And just.
I will just point out that, while it targets the SCF-248, it is not a neutralizing stem cell factor antibody. It has a different mechanism, which they describe as inducing the internalization of that particular isoform of SCF, so definitely a different approach.
All right. That's an important point. Awesome. And what's the timing for the MAD data for 622?
We've disclosed that Q3 2026.
OK. Awesome. All right. For Barzol then, for CSU side, you're enrolling all comers, so prior omalizumab, post- omalizumab patients. I guess thinking commercially, how much of the use do you think is going to be prior omalizumab as opposed to post- omalizumab ?
Initially, we think it'll fall behind omalizumab , right? O malizumab has been around for a long time. The allergists have used it for over 15 years. We think that on the normal scale, it will be behind omalizumab . Now, will there be those cases where a patient is considered severe either by angioedema, poor quality of life, a high UAS-7 score? We think that there are doctors that will certainly give Barzol well before that. But the fact that we know we can target both the antihistamine refractory population and the biologically experienced and the biologically refractory population, it's going to be used variously in a number of different areas. I think that we're going to be happy about that, that we can sit here and say, hey, we can target the whole population. When and where that happens, only time is going to tell.
And again, you want to get a good launch going. You want to get it out there as much as you can. And then over time, you want to be the drug of choice in the disease area.
Awesome. So I asked this same question last year. I actually checked consensus numbers, and I'll ask it again this year. I'm seeing consensus has your pricing at around $40,000 a year. If I think about a lot of the other analogs in immunology, especially acknowledging a lot of the use is going to be in a post-biologic population off the bat. Looking at the analogs, shouldn't your price essentially be double that range?
I think it's higher than $40,000. I think when you asked that question last year, Galderma wasn't, Nemluvio wasn't approved, and that came out at $59,000. I think it's certainly going to be much higher than that. How much? We'll have to see. Obviously, the 76-week data showed us a lot, the fact that we can treat for 12 months and get benefit for 19 months for the patient. That will be a discussion you have with the payers, per se. That's why we have market access people to go in and have those conversations. We will certainly look for a premium on that.
Yeah. All right. That makes sense. That makes sense. And have you said the mix of prior or post- omalizumab patients coming into the phase IIIs, not that it probably impacts efficacy all that much?
I think in the phase II, it was probably, what, 20% that were omalizumab refractory. So we think that that percentage in the experienced refractory would still match up. We may see some more patients that are other than omalizumab . We may see dupilumab . We may see remibrutinib, but definitely most of them are going to be omalizumab .
Yeah. All right. That makes sense. I don't know how much work you guys have done on the commercial side on this point, but the number of patients who are on omalizumab today in the U.S., I think Novartis has noted around 80,000. Is that roughly what you've kind of triangulated on from your own research?
A little bit higher, only because, like I said, we can handle the whole population. So the numbers are probably 40% higher than that.
Yeah. Awesome. All right. On the AD side of things, I think my number one question for this indication has always been patient selection. And I don't know how to go about this, right? You can kind of look at patients who have residual itch as a kind of a proxy for mast cell activity. You could go based on prior treatments. You could go on IgE high or low or an eosinophil count too. Do you think patient selection is going to be a relevant consideration on the atopic derm side? How do you think about it?
Yeah. So I think eventually, and especially since there's so many new agents in development and new agents getting approved, I think that that is definitely the direction that the research is going to take. I would say it is a heterogeneous disease. So we've decided to do our study really in all comers without trying to guess what would be a responsive population, just to see how we do. And then we'll study and see if anything sorts out as far as more likely to respond.
Yeah. That makes sense. I mean, is there any consideration on AD patients that have other comorbid atopic conditions? Is that being kind of a good segment to go after?
We'll certainly look at that. I mean, we're going to gather all that data and see how that pans out. I did also want to mention that in our study, we are allowing people who have had virtually any prior therapy for AD as long as they've washed out of it. So we may get some information on response in people who have had other treatments and things like that, which we'll certainly look at.
Do you allow for concomitant steroid use on the topical side during the study?
In our study, we don't.
OK. Got it. That makes sense. On the PN side, don't you know your dose already for PN? If you know the dose, why not just upsize this trial, use it as a registrational and go file?
No, that's a great point. We actually know that we have to do two studies. If you look at dupilumab and you look at nemolizumab, they both had to do two studies. FDA wants to see replicate results. I think in terms of dosing, we had the phase I-B study, which was IV dosing. And we decided to go into the phase II with two different regimens, but they're both subQ regimens. And they're a bit higher than what we looked at in CSU, and they have a loading dose. So I would say once we're done with this study, we'll have a good idea of our dose. And then hopefully, we can streamline whatever we need to do for registration.
Awesome. And what do you think about additional indications for Barzol moving forward?
Additional indications?
Additional indications, yeah. Any you're considering, any thinking about going after? I mean, you also have 622 advancing, right? So that's kind of where some of the resources are going to go.
Yeah. Some of the additional allergic diseases we were thinking about, food allergy is certainly a consideration. Certainly, I want to see the PN data and look at whether CIP is another indication, and then allergic rhinitis and so on and so forth. So there are a number of things that we're looking at. Certainly, we want to be able to score them properly and then move forward.
Yeah. And I guess on this topic then, what do you think about partnership opportunities too, given two assets, broad indication potential, late-stage development at this point?
We're thinking about it. I mean, obviously, you have to think about it. But especially now with Barzol ready to flip the card at some time in 2026, that's something that we would take forward ourselves if we can in the United States. I mean, outside the U.S., we've always said that we would look for a partnership. But we've gone through the tough part. We're bringing in people on the commercial side to help with that heavy lifting. So we'll see. We remain positive on it.
Awesome. We have two minutes. Maybe let's actually go back to 622 for a second. So after you get the MAD data third quarter of next year, what's your plan on the next study that you're going to run?
I think what we're hoping is we address all the questions related to basic safety, immunogenicity. Give us the confidence that investing in significant phase II trials makes sense for this molecule. Everything looks good so far. The asthma study is going to be an open label study. We'll be having data from that. I think the intention is to go into randomized phase II trials backed by sufficient data that really supports that investment.
Yeah. There's something I've wondered too. If you were to run a CSU study for 622, and let's say the efficacy is very close to Barzol, why not, like a broader life cycle management strategy, why not go full steam into SCF instead of c-Kit.
Obviously, we're extremely pleased. We hit Barzol and aren't looking at it as a life cycle. We're really looking at it as indication expansion opportunities, not just with 622. But this is our first molecule in this pipeline of SCF-targeted molecules where we have other combinations targeting specific indications based on the combination of targeting stem cell factor or mast cells with other. So we're really looking at this molecule now really is to validate the platform and to allow for expansion. Certainly, there's opportunity to consider broader access with that. But at least initially, this is our goal with the 622 program.
Perfect. I guess my last closing question, what are you most excited for next year?
The CSU data obviously is that we're most excited for. And again, we think the future is extremely bright. We've got five indications that we think Barzol will work very, very well. And with 622 and the other things that Tibor has got in his pipeline, I think the future looks extremely bright.
Awesome. Right on time. So we'll wrap it up there. Thanks. [crosstalk]