Please be advised that today's conference is being recorded. I'd now like to hand the conference over to Sarah Cavanaugh. Please go ahead.
Thank you. Good afternoon, and thank you for joining us to discuss the top-line results from our phase II barzolvolimab program in eosinophilic esophagitis, or EoE. Joining me on the call today are Anthony Marucci, Co-Founder, President and CEO; Dr. Tibor Keler, Co-Founder, EVP and Chief Scientific Officer; Dr. Diane Young, Senior Vice President and Chief Medical Officer; Dr. Margo Heath-Chiozzi, Senior Vice President of Regulatory Affairs; and Dr. Diego Alvarado, Vice President of Research. Please note the slides for today's call are available in the Investor Relations section of our website. Before we begin our discussion, I would like to direct your attention to slide two with respect to important information regarding the forward-looking statements that today's speakers will be making. Please be advised that a question and answer period will be held later in this call. I'd now like to turn the call over to Anthony.
Thank you, Sarah, and good afternoon, everyone. Today we are reporting top-line results from our phase II study of Barzo in EoE. As many on this call know, identifying the key drivers of this difficult-to-treat disease has challenged the field over the years, and patients continue to need more effective treatment options. The depletion of eosinophils has not consistently resulted in improved clinical outcomes, but patients and research in the field have suggested that other cell types, including mast cells, could play an important role in the disease pathogenesis. As we explore barzolvolimab with more than that full potential as a mast cell inhibiting agent, we are leading important contributions to the emerging science that defines which diseases are ultimately mast cell driven.
In studies conducted in chronic spontaneous urticaria, cold urticaria, symptomatic dermographism, and pruritus nodularis, we demonstrated barzolvolimab's ability to profoundly deplete skin mast cells and impact disease symptoms, which supported continued development in these indications and atopic dermatitis, which, like PN, is an itch-driven skin condition. We designed the phase II study in EoE to determine if barzolvolimab could deplete mucosal mast cells in the GI tract and in turn improve clinical outcomes in this disease. Results from this well-run study were clear and confirmed that barzolvolimab profoundly depletes mucosal mast cells, but the depletion of mast cells did not result in improvements in the EoE symptoms. We are disappointed in this outcome, especially for patients who need more treatment options.
We have repeatedly said that we needed to not only see profound impact of cell depletion, but also a reduction of the endoscopic scores that would be clinically meaningful and compare favorably to the current standard of care. These results did not meet our internal hurdle rate, and we will not advance development in this indication. Diane will walk you through the data tonight, and we will answer as many questions as we can. That said, there is a significant body of data associated with the study, and our team is currently working through the top-line analysis, which we just received, and additional data still to come. The Celldex team is committed to advancing mast cell science and its impact on important diseases, and we plan to publish these results in the future as we feel it is important for the field for both mast cell science and EoE.
Before I turn the call over to Diane, I would like to thank all the clinical trial investigators, site staff, and patients involved in this trial. Diane?
Thank you, Anthony. Good afternoon, everyone. Let me start by reminding you of the study design outlined on slide three. This study is a randomized, double-blind, placebo-controlled, parallel group trial. Sixty-five patients with active EoE were randomly assigned on a one-to-one ratio to receive subcutaneous injections of barzolvolimab at 300 mg every four weeks or placebo during a 16-week placebo-controlled treatment phase. Following completion of the placebo-controlled treatment phase, all patients entered a 12-week active treatment phase and received barzolvolimab at 300 mg every four weeks. Patients then entered a follow-up phase for an additional 16 weeks. Endoscopies were conducted at baseline, weeks 12, and 28. The primary endpoint of the study is the reduction of esophageal intraepithelial or mucosal infiltration of mast cells as assessed by peak mast cell count at 12 weeks.
Secondary endpoints include the reduction of dysphagia, reduction of eosinophils in the esophagus, and safety. A key exploratory endpoint for the study was the endoscopic scoring of EoE-related inflammation and fibrosis, or the ERAS scale, as it is more commonly called. Dosing is complete in the study, and patients are being followed as per protocol. As you can see on slide four, demographics and baseline disease characteristics were generally well-balanced across treatment groups. Patients on the study were highly symptomatic and had moderate to severe EoE, as indicated by high baseline peak mast cell and eosinophil counts and dysphagia symptom questionnaire, or DSQ, scores. Slide five outlines the primary endpoint, which the study clearly met: the absolute change in peak intraepithelial mast cell counts from baseline to week 12.
Peak mast cell counts, as measured by CD117 or KIT positive cells per high power field at baseline, were 50.3 in the placebo arm and 55.4 in the barzolvolimab at 300 mg every four weeks arm. At week 12, the absolute change from baseline was a decrease of 2.7 cells per high power field for placebo compared to a 36 cell per high power field change from barzolvolimab . The result was highly statistically significant, with a p-value less than 0.0001. We also analyzed the change in intraepithelial mast cells using tryptase staining, which may be more specific to mast cells in the esophagus. In barzolvolimab treated patients, there was a 75% depletion at week 12. Based on available data, this depletion continued to deepen to approximately 90% at week 28.
This finding is important because it confirms that barzolvolimab profoundly depletes both cutaneous and mucosal mast cells. Identifying the key drivers of EoE has been a challenge for the field. A growing body of evidence suggested that mast cells might play an important role in the disease. We demonstrated barzolvolimab's ability to profoundly deplete mucosal mast cells, but we now know that this did not result in improvement in clinical outcomes, providing direct evidence that mast cells are not a primary driver in EoE, as you can see in the secondary and exploratory endpoints outlined on slide six. The first box shows the change from baseline in the dysphagia symptom questionnaire at week 12, where there was no improvement observed compared with placebo.
This was echoed in the change from baseline endoscopic evaluations, as measured by endoscopic scores outlined in the second figure on this page, where there was also no improvement over placebo noted. We were also surprised, based on the close interaction between mast cells and eosinophils, by the lack of eosinophil depletion depicted in the chart on the right. In order to determine whether a longer duration of barzolvolimab treatment would have improved outcomes, we conducted an unblinded review of all available data through the full 28-week treatment period and the full 44-week study, and the results for these endpoints are consistent with the results at 12 weeks, despite deepening profound mast cell reduction.
While this is not the outcome we wanted, our work here answers a key question about the involvement of mast cells in this disease, and we are hopeful these findings will support the advancement of EoE research and the drive for more effective therapies for patients. Another important finding was the continued confirmation of barzolvolimab's favorable safety profile outlined on slide seven. This is our first study evaluating this more frequent every four-week dosing regimen of barzolvolimab at 300 mg, and the safety profile is consistent with prior studies with less frequent dosing. The most common adverse events observed in 10% or greater of barzolvolimab treated patients were hair color changes, nasopharyngitis, or the common cold, and fatigue.
The hair color changes were grade one events with a single grade two and mostly occurred in the beard, which is fast cycling hair, especially in men who shave regularly. These changes have either resolved or are resolving with follow-up. Four patients discontinued related to adverse events on the placebo arm, and one patient discontinued on barzolvolimab, reporting hair and face changes. There were no treatment-related FAEs on the barzolvolimab arm. Again, these safety findings are highly supportive of barzolvolimab's overall safety profile, and we were pleased to see this consistency with the more frequent dosing regimen of 300 mg given monthly. In summary, on slide eight, there were a number of key learnings in this study.
We have now demonstrated that barzolvolimab depletes mucosal mast cells as well as cutaneous mast cells, as demonstrated in prior studies, which supports broad future development of KIT or stem cell factor-targeted therapies, including in other GI conditions where mucosal mast cells are believed to play an important role. Broad mast cell depletion did not result in improved clinical outcomes in EoE, providing direct evidence that mast cells are not a primary driver in this setting, furthering the scientific understanding in EoE. We will complete the phase II study, but we will not pursue further development in EoE. Lastly, we were pleased to confirm barzolvolimab's favorable safety profile at 300 mg in a more frequent dosing regimen. With that, I will turn the call over to Anthony to close. Anthony?
Thank you, Diane, and thank you all for joining us. While we are disappointed in the clinical outcome in EoE, we are proud of our progress and continued execution. We remain committed to leading the science and the exploration of mast cell biology to deliver life-changing therapies to patients in need. Barzolvolimab has significant potential to become a transformational medicine for patients, and we continue to work to determine which disease settings offer the best opportunities for future success. As you can see on slide nine, barzolvolimab is currently being studied in five indications, including two phase III studies in chronic spontaneous urticaria, and two phase II studies in cold urticaria, symptomatic dermographism, atopic dermatitis, and pruritus nodularis. We are also preparing to initiate a phase III program in cold urticaria and symptomatic dermographism.
We look forward to continuing to update you on our progress as we advance these programs and additional candidates from our KIT and stem cell factor pipeline. We appreciate your support in this endeavor and look forward to answering your questions tonight. Operator?
If you'd like to ask a question at this time, please press Star, one, one on your touch-tone phone and wait for your name to be announced. To withdraw your question, please press Star, one, one again. Please stand by while we compile the Q&A roster. Our first question comes from Thomas Smith with Leerink Partners.
Hey guys, good afternoon. Thanks for the update here and thanks for taking the questions. The first question on safety, I think it looks really clean here through that 16-week treatment period. Can you just comment on what you saw out beyond that time point? I think you mentioned kind of an unblinded review of the data that we had beyond the 16 weeks. Could you just comment on that time point and were there any other patients who discontinued treatment with longer dosing?
The data is not complete, but we do have data on the majority of patients, so I can just generally say that the safety profile further out is very consistent with what we're seeing, and there's really no additional signals there.
Okay, got it. That's helpful. Just to follow up on the dosing, if I could, obviously the mast cell depletion here looks really strong. Could you talk about the kinetics that you saw here with the 300 mg q4 week dosing, and then talk about your level of confidence in the two dose levels that you're using in the phase III CSU program?
As far as kinetics for the immunohistochemistry, those are from the 12-week and week 28 analysis. We don't have fine-tuned kinetics based on when we took the biopsies, but our expectation is that we have very profound depletion. As you said, it occurs quickly and further gives us confidence overall for our phase III programs.
Got it. That's helpful. If I could just sneak in one last follow-up just on the neutrophil count, if you could just comment on any grade 3 neutropenia that you observed or I guess the consistency of the experience here relative to the existing bars of experience, that would be super helpful. Thank you so much.
Yeah, we had just one adverse event of neutropenia, which was a grade 2 and resolved while on study. The curve for the neutrophil counts looks very consistent with what we've seen with all of our other programs.
Thank you, Tom.
Our next question comes from Yaron Werber with TD Cowen.
Great. Thanks for taking the question and for doing the call. The pruritus nodularis phase II, it's ongoing. Based on that positive phase 1 data, it looks like it's a 24-week study, 120 patients, right? One to one to one. It seems like it's still enrolling, but the primary completion on clinicaltrials.gov looks like it's early next year. It looks like we're potentially on track for data in the first half of next year. Can you, I know you haven't given that, but can you, does that make sense? Secondly, just on safety, are there any hypersensitivity or any anaphylaxis or any sort of rare AEs that popped up in the study? Thank you.
Sorry, Jaron, why don't we have Diane take the second question first, and then I can give you a timing on the data at the end.
We did not see anaphylaxis in the study. Really, nothing as far as hypersensitivity, and there were no related serious adverse events in marginal treatment patients.
Yeah. Yaron, what it says on clinicaltrials.gov is how we're tracking. I think it'll be data sometime in 2026, but as we get closer, we can certainly fine-tune as to when we'll have that data. It will be sometime in 2026.
Our next question comes from Kristen Kleska with Cantor Fitzgerald .
Good noon, everybody. Clearly not the results you wanted, but importantly, it did have a good mechanistic rationale here for depleting the intraepithelial mast cells. Curious, as you think about future innovation and indications for Celldex, how do these data help kind of fine-tune where you may consider looking next and what that rationale may be? Thank you.
Kristen, you really want to take it from a biologic standpoint, and you have an emergency answer or anything else?
Hi Kristen. I think what we learned about here was mostly related to EoE with regards to the potential lack of a driving role for mast cells. I don't think there's a lot of read-through through many other indications. This is a really unique and difficult-to-treat disease. Clearly we have to do our homework. What I do think is that we appreciate that mast cells have a real important role, but may not always be drivers in a number of indications, and that's really what led us to develop our bispecific antibody approach. We're targeting mast cells along with other pathways. It may really be what's needed in certain indications. Our future is really working through also understanding what other pathways work in conjunction with mast cells, and you'll see that as we roll out some of our bispecific programs.
Thank you.
Thanks, Kristen.
Our next question comes from Judah Frommer with Morgan Stanley.
Yeah, hi guys, thanks for taking the question. Maybe sticking with EoE and I guess potential additional analyses. I think it's become better understood in the last few years that there are varying potential endotypes for EoE. Just curious how you're thinking about maybe further investigating the data you have. Is there an opportunity to do sort of sub-cohort analyses based on endotypes or any other defining factors between groups, or if that's just not worth your while?
I know we certainly have a lot of data to go through, and we're anxious to get as much out of this study as possible based on all the biopsy and opportunities. The challenge with a lot of subgroup analysis is the size of this study will be difficult to give really significant evaluation with regards to the numbers that fall into a particular endotype or have specific disease characteristics. We do plan to do the work and certainly will be presenting on that.
Yeah, Judah, we'd rather be helpful here. Even though if it didn't work out for us in EoE, we think there's enough data that we could be helpful in giving out some information based on any kind of analysis we'll do. We'll definitely do that.
Thanks.
Our next question comes from Sam Slutsky with LifeSci Capital.
Hi, good afternoon. Thanks for taking the question. I guess since you won't be progressing in EoE anymore, is there room to add an additional indication to the pipeline over the next year? Can you just discuss how you're thinking of new indication selection between barzolvolimab versus CDX-622?
Yeah, we intend on adding additional indications going forward, Sam. As we always said too, we'd like to get data from our studies to give us additional insights. We know what we want to go after, but we want to see if some of the studies that we have correspond, that we can get some cohorts or patients with comorbidities that would fit what we want to go after. As far as looking at CDX-622 versus barzo, we're going through that process now. Obviously, there are different types of diseases we can go after with CDX-622 that wouldn't necessarily be top of mind with barzo, but we'll get more clarity around that as the year ends, and we'll just be happy to discuss that with you.
Okay. I guess just real quick on that potential indication expansion, is that something we might get insights on next year, or is that kind of 2027? How are you thinking on that?
That's probably next year. As these data sets come out, we'll get more information. I think we have our list. We're just looking for more clinical data to have a check of box for us. It'll be sometime in 2026.
Okay, thanks.
Our next question comes from Yatin Suneja with Guggenheim.
Hi, this is Iris on for Yatin. Thanks for taking our question and thanks for the update. It's a really important piece of the scientific bubble. My question is about the safety. Would you be able to provide a little bit more color on how soon do you see the hair color change based on this continuation of the blinded data? Would you expect to disclose the full safety data at some point? Thank you.
Diane?
The pattern of hair color changes is similar to what we've seen so far. We haven't done a complete analysis of that yet. We're still looking at top-line data as Anthony indicated, and we will plan to publish these results at some point.
Thank you. If I may have a follow-up question, are there any other GI indications you think this MOA would be applicable? Thank you.
For barzo?
Yes.
We do think that there are certainly other GI indications that have a different biology than what we see in EoE where we do know that mast cells play a role. We will investigate them. It may be something that's better tackled with our bispecific approach than barzo specifically, but we are looking into additional GI indications.
Yeah, understood. Thank you so much.
Our next question comes from Richard Law with Goldman Sachs.
Hey guys, this is Patterson on for Richard. Maybe just a quick question on the DSQ scores. Do you think that there's any possibility that it could have just taken more time for symptomatic changes to play out if you were to extend this study? Is there anything specifically about your patient baseline characteristics that you think could have contributed to the negative result? Some of the things we noted just looking at this study versus DBIs was patients had higher eosinophils and I think greater history of esophageal dilation. Things like that. Thanks.
We are definitely going to do more analyses to try to understand. We see the same things that you're describing in the demographics, and I think that is something we should look at. The data that we have looked at in the study really does not suggest that longer treatment is going to have an improvement in symptoms. There really is not an improvement in symptoms, although the mast cells have a deepening of response. We don't believe that longer treatment gets a greater benefit.
I remember we were very clear. We wanted to see the impact on the mast cells, which we did see, but we also wanted to see the stages for similar to what's currently standard of care. Once we know we didn't meet those, it was, you know, we put it to bed.
Got it. Thank you.
Thank you.
Our next question comes from Alex Thompson with Stifel .
Hey, great. Thanks for taking our questions. I guess shifting gears to your ongoing phase III CSU study, I wonder if you could comment on the progress there, expectations around timelines, and what portion of patients have been dosed with multiple doses at this point? If you're seeing any blinded signals around anaphylaxis, hypersensitivity, or other severe adverse events. Maybe as a follow-up too, can you talk about your confidence in the underlying mechanism here in pruritus nodularis and atopic derm, just given the results today? Thank you.
As far as the phase III goes, Alex, we said that we've got it to two years' rolls and that we're happy where we are. As far as talking about efficacy or safety of an ongoing study, we won't do that. We'll wait for the study to be completed. As far as a read-through of this to atopic dermatitis, that's absolutely no read-through. We think that the better read-through is PN. PN, we saw some good data in our phase 1b and some other evidence from other studies. We absolutely see no correlation between this and atopic dermatitis. PN is the indication you'd want to look at.
I guess as a quick follow-up, would you say no news is good news on the phase III as it relates to severe safety signals?
No news is good news, right?
Okay, thank you.
You're welcome, Alex.
That concludes today's question- and- answer session. I'd like to turn the call back to Anthony Marucci for closing remarks.
Thank you, operator. As I said earlier, there's a significant body of data associated with the study, and our team is currently working through the analysis. We will use what we learn to continue to drive innovation in mast cell science and deliver life-changing therapies for patients. Thank you all for joining us this evening and have a good night.
This concludes today's conference call. Thank you for participating. You may now disconnect.