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

Good evening, and thank you for standing by. Welcome to the Celldex Therapeutics Corporation Update Conference Call. [Operator Instructions] Please be advised that today's conference may be recorded. [Operator Instructions] I would now like to hand the conference over to your host today, Sarah Cavanaugh. Please go ahead.

Good evening, and thank you for joining us tonight to discuss interim results from our Phase Ib multiple-ascending dose study of barzolvolimab in patients with chronic spontaneous urticaria, which were released tonight at the EAACI 2022 Annual Meeting. On our call this evening, I have Anthony Marucci, Co-Founder, President and CEO; Dr. Diane Young, Senior Vice President and Chief Medical Officer; Dr. Tibor Keler, Co-Founder, Executive Vice President and Chief Scientific Officer; Dr. Margo Heath-Chiozzi, Senior Vice President of Regulatory Affairs and Medical Lead of the program; and Dr. Diego Alvarado, Executive Director of Research and Research Lead on the program. We're also very pleased to welcome Dr. Marcus Maurer, Professor of Dermatology and Allergy at Charité in Berlin. Dr. Maurer is a mast cell expert focused in urticaria. He conducted our Phase Ib study in chronic inducible urticaria and is a lead investigator in our ongoing CSU study. He also presented this evening interim results at EAACI and will provide his perspectives on this data on our call tonight. Given the time difference, he will not be able to join us for Q&A on this call but has graciously offered to be available for investor questions at EAACI or one-on-one. In the Investors section of the celldex.com website, you will find today's press release, a copy of the EAACI presentation and the slides we will refer to on this call, which are all located on the Events & Presentations page. Before we begin our discussion, I would like to direct your attention to Slide 2 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 would now like to turn the call over to Anthony.

Thank you, Sarah, and thank you all for joining us this evening. We are very excited with the interim results from the study as we represent an important step forward in the clinical development of barzolvolimab. We have confirmed barzolvolimab's favorable safety profile in the multi-dose setting and demonstrated outstanding clinical activity across multiple clinical assessments even at this early time point that exceeds the standard of care. We observed rapid, marked and durable responses in a severely symptomatic CSU patient population, including in patients with prior Xolair experience for whom there are no currently approved treatment options and where several recent clinical studies of new medicines for this patient population have been unsuccessful. From a scientific perspective, this study also provides direct evidence on the critical role of mast cells in CSU and speaks of barzolvolimab's unique mechanism of action as a mast cell depleting agent, which further supports our continued expansion into our other mast-cell-driven diseases. At this time, I'm going to ask Diane to walk you through the data, which represent our first multi-dose, placebo-controlled data in chronic spontaneous urticaria. Diane?

Thank you, Anthony. I want to echo Anthony's enthusiasm. Following the compelling data we presented in chronic inducible urticaria, or CIndU, at EAACI last year, we have now established clinical proof of concept in a second form of urticaria with the data presented tonight in chronic spontaneous urticaria. CSU is a disease of misery for patients. Unlike CIndU, the itch and hives have no identifiable triggers. It has long been considered that mast cell activation drives the disease, resulting in the intense itching, hives and swelling of the skin that can go on for years or even decades. These symptoms often impact patients' lives far beyond their physical health, including all aspects of their personal lives, self-esteem, mental health and job performance. Unfortunately, it is a common disease with up to 1% of the total population affected. Current therapies provide symptomatic relief only in subsets of patients. The first step in treatment is antihistamines, which relieve symptoms in only about half of all patients even when escalated to 4x the approved dose. Antihistamine-refractory patients are typically treated with omalizumab, which is also only effective at controlling urticaria symptoms in about half of these patients. And for the remaining 50% of patients where omalizumab doesn't adequately control their disease, there are no approved options. Barzolvolimab is a humanized monoclonal antibody that targets the receptor tyrosine kinase KIT, which is a critical receptor for mast cell function and survival. Based on this unique mechanism of targeting mast cells which are believed to be the root cause of the disease, barzolvolimab has the potential to broadly impact urticarias and other mast-cell-driven diseases. Before I review the results, let me provide an overview of what the presentation covers. Tonight's presentation included interim data from our ongoing Phase Ib randomized, double-blind, placebo-controlled, multiple-ascending dose study in patients with moderate to severe antihistamine-refractory chronic spontaneous urticaria, including those who have received prior biologics. The study design is outlined on Slide 5. The study includes 4 dose cohorts, 0.5, 1.5, 3 and 4.5 milligrams per kilogram. The 2 lower doses are given at week 0, 4 and 8, and the 2 higher doses are given at week 0 and 8. The study is a 24-week study with a 12-week treatment period and a 12-week follow-up period. Each blinded cohort included at least 8 patients treated with barzolvolimab and 2 patients treated with placebo. Placebo was included in the study to more objectively assess the primary end point of the study's safety and tolerability. The placebo patients from each cohort were pooled for this analysis. We used the following standard assessments to evaluate clinical activity: the Urticaria Activity Score 7, or UAS7, which is comprised of the Hives Severity Score and the Itch Severity Score and the Urticaria Control Test, or UCT. The data cutoff for the presentation was May 23. Given that the study is still ongoing, we were unblinded by dosing groups, but remain blinded to individual patient level data. Through the May cutoff, all patients in the first 2 cohorts had completed study participation through 24 weeks, and the patients in the third cohort, which is 3 milligrams per kilogram of placebo, were ongoing. The 4.5 milligram per kilogram cohort is still enrolling, and data from this group are not included. For safety, we presented all available data on adverse events. For hematology parameters, we presented data through the active treatment period of 12 weeks for the 0.5 milligram and 1.5 milligram per kilogram dose groups and all available data through 12 weeks for the 3 milligram per kilogram and placebo dose group. 12 patients were enrolled in the 3 milligram per kilogram or placebo cohort, and 7 of 12 had completed the 12-week treatment period as of the data cutoff date. For clinical activity, we presented data through 12 weeks for the 2 lower dose groups, 0.5 milligrams per kilogram and 1.5 milligram per kilogram, which reflects 3 doses administered every 4 weeks. For the 3 milligram per kilogram group, we presented clinical activity data through week 8, a time point which all patients in the cohort had crossed as of the data cutoff date. I want to point out that this means the current data set only reflects a single dose of barzolvolimab at 3 milligrams per kilogram for the purposes of activity, but 2 doses for safety and hematology in today's presentation. As outlined on Slide 6, the patient population enrolled in this study is highly symptomatic with mean baseline scores in UAS7 ranging from 29.4 to 36.6, representing severe disease. Many patients have been struggling with their disease for multiple years, and nearly 50% have received all approved treatment options, including omalizumab, for which the majority had an inadequate response. Furthermore, mean baseline UCT scores of 1.7 to 3.4 also indicate poor disease control. Given these baseline characteristics, we were very pleased to see outstanding clinical activity. On Slide 7, you can see that patients experienced rapid, marked and durable decreases in itch and hive symptoms as measured by UAS7. All doses were clinically active with a mean percent reduction from baseline for UAS7 of 39.7% for the 0.5 milligram per kilogram dose group at week 12, 66.6% for the 1.5 milligram per kilogram dose group at week 12, and 75.1% for the ongoing 3 milligram per kilogram dose group at week 8 with only 1 dose included for clinical activity measurements. The corresponding numbers for placebo patients are 35.9% at week 12 and 31.1% at week 8. Of great importance to patients and their physicians, as shown on Slide 8, a similar magnitude of improvement in mean UAS7 scores was seen in the more than 40% of patients with prior omalizumab experience that received barzolvolimab. These data speak to the clear role of mast cells as drivers of urticaria and to barzolvolimab's unique mechanism of action as a mast cell depleting agent. Dramatic improvements in both itch and hives resolution, as outlined on Slide 9, drove these changes in UAS7 numbers. Here, you can clearly see rapid onset as soon as 1 week after the first dose. Slide 10 shows the percentage of patients who achieved complete response by UAS7. Our clinical activity goal for this study was to be as good or better than the standard of care for antihistamine refractory patients. In this population, omalizumab has demonstrated a UAS7 equal to 0 or complete control of disease at 12 weeks reported as 36% in the label. We have shown activity across all 3 dose groups with 57.1% complete control of symptoms in the 1.5 milligram per kilogram dose group at 12 weeks. At 8 weeks with only a single dose of 3 milligrams per kilogram, the complete control rate was 44.4%. The corresponding number for placebo was 16.7% at 12 weeks and 0% at 8 weeks. As expected, the low dose of barzolvolimab at 0.5 milligrams per kilogram demonstrated a suboptimal 11.1% complete control rate at 12 weeks. Urticaria control, which is an important assessment used in routine clinical practice, is presented on Slide 11. UCT is a patient-reported outcome measure assessing urticaria's symptoms, effective treatment, quality of life and urticaria control over the last 4 weeks, which is validated in both CSU and CIndU. Patients entered the study with a UCT mean values ranging from 1.7 to 3.4, representing very poorly controlled disease. UCT scores greater than or equal to 12 represent well-controlled disease, which was noted in 75% of patients in the 1.5 milligram per kilogram dose group at week 12 and 83% of patients in the 3 milligram per kilogram dose group at week 8. The magnitude of UCT score improvement of 8 points is similar to the level of improvement seen in our Phase Ib CIndU study. On Slide 12, we present rapid and profound reduction in serum tryptase, which we've demonstrated is indicative of skin mast cell depletion and is associated with greater clinical activity, in particular, complete and more sustained response. Turning now to safety. The primary end point of this Phase Ib study was assessing safety and tolerability associated with the administration of multiple ascending doses of barzolvolimab. We are pleased that, as expected, barzolvolimab continues to demonstrate a favorable safety profile. Adverse events were mild to moderate in nature, all resolving on study with none leading to treatment discontinuation. Slide 13 shows the adverse events that occurred in more than 10% of barzolvolimab-treated patients, urinary tract infections, headache, neutropenia and back pain. UTIs, back pain and headache were all reported as not treatment related. The UTIs occurred at a similar rate in placebo and treated patients with half of the UTIs reported during active treatment and half reported during the 12-week recovery period, all cleared with standard antibiotic therapy. There was one serious adverse event of salmonella gastroenteritis, which was also not related to study therapy. The only treatment-related adverse event reported in 10% or more of patients was asymptomatic neutropenia. On Slide 14, we have graphed the hematology parameters, which were closely monitored in this multiple ascending dose study. The hematologic changes overall in the multi-dose CSU study across all parameters are consistent with our prior single-dose studies with no pattern of further decreases with multiple doses and no clinical consequences associated with these laboratory findings. As seen in prior studies, neutrophil declines are typically observed within 1 month following a patient's first dose. Importantly, as we expected in this study, there was no progressive decline observed with additional doses. Four patients, 2 in the 0.5 milligram and 2 in the 1.5 milligram per kilogram dose groups had decreases in neutrophil counts reported as adverse events. The screening and baseline neutrophil counts for these patients were at the lower end of the normal range when they initiated the study. The pattern observed in the neutrophil changes for these patients was similar to the pattern seen in patients across the barzolvolimab program to date, generally transient, asymptomatic and mild decreases, and did not cause delay in their dosing. Interestingly, findings previously noted more commonly, such as hair color changes and taste changes and infusion reactions, were seen in less than 10% of patients in this study. We are pleased that the data thus far confirm that additional dosing and exposure continue to support the favorable safety profile of barzolvolimab. Importantly, these safety data were reviewed in an ongoing fashion with the independent data review committee, the investigators and the Celldex medical team without concern. In summary, the favorable safety profile in a multi-dose setting and the excellent clinical activity data found in this study continue to add to our growing excitement for the barzolvolimab program in chronic urticaria and other mast-cell-driven indications. We believe we have an active, well-tolerated drug and look forward to further characterizing its potential in the ongoing Phase II studies we initiated earlier this month. I'd now like to ask Dr. Maurer to share his thoughts on the study results Dr. Maurer and his clinical sites have played an important role in the study of treatment for chronic urticarias and his deep knowledge of mast cell biology and chronic urticaria have been invaluable to Celldex in our work on the barzolvolimab program. Dr. Maurer?

Well, thanks, Diane. I'll be very happy to comment on these results. Actually, we are very excited about these data, these insights. There's a lot of firsts here. This is the first time we're looking at multiple dosing. This is the first time we have placebo-controlled data. And what we see in these patients, not just the data but the way they feel when being treated, it's marvelous. And to me, as a mast cell biologist, it is extra exciting because it confirms the concept that all chronic urticaria is mast cell driven, mast cell dependent. We saw from the chronic inducible urticaria patients just how well barzolvolimab works and to reproduce that now in the chronic spontaneous urticaria patients, that's really, really cool. And to hit mast cells and still see this very well-tolerated treatment work over time with multiple dosing, that just is very promising and further encourages the development for barzolvolimab to be a chronic urticaria drug, for both chronic spontaneous urticaria and chronic inducible urticaria. So the efficacy, when I first saw the data reminded me of omalizumab or better, that's how I would like to phrase that. We looked at all the outcomes that were also looked at in omalizumab-treated patients with chronic spontaneous urticaria and to have UAS7 of 0, which is the goal of treatment per guideline in close to 60%. That's great. That's what we need, especially since we know that many of these patients were experienced with omalizumab and had not shown a satisfactory response to omalizumab. And mind you, we're still looking at data that mostly comes from the low dose. So we are very much looking forward to the rest of the data that will come from the 3 milligram per kilogram cohort and, of course, more details to come on this dose as we move forward. Now I also really like that the urticaria control test was included in this study. It really is our go-to measure in routine clinical factors and to see that 75% of patients in the 1.5 cohort at week 12 and more than 80% in the 3-milligram cohort at week 8 achieved controlled disease. Now this is very rewarding and very exciting. Also nice to see, of course, that tryptase is confirmed as a marker, but the more exciting outcome to me as a clinician and urticariologist is that we see this remarkable response reproduced in chronic spontaneous urticaria patients previously described in chronic inducible urticaria. And as for safety, I know there were discussions, would it be different to dose ones or to receive multiple doses of barzolvolimab and to see that it's pretty much the same? There's no new safety signal here. This -- what we see here is consistent with the prior single dose, including hematological changes. So it appears to be a very well-tolerated and safe treatment. And yes, while we continue to try to figure out what it is that explains some of these transient and moderate adverse events, we are fairly certain that it hasn't got anything to do with mast cells and that this is not something that would stop us from using this drug in the routine clinical setting. So I'm very excited to have these encouraging results, further supporting the development. I hope that we will make progress soon. And I realize that there are millions of chronic spontaneous and chronic inducible urticaria patients out there who right now cannot be helped. And to have a potent treatment like barzolvolimab, which is at the same time well tolerated and safe, is just very exciting to see for our field and for urticaria patients globally. So well, we are looking forward to more results to come, but I'm very happy with what we've seen so far. And I will be happy to answer any questions or to provide more info on how I see these data, if you would like. Thank you very much.

Thank you, Dr. Maurer, for your insights this evening. These data clearly support the continued development of barzolvolimab, including our recently initiated Phase II subcutaneous chronic urticaria studies. Last week, we announced the first patient has been dosed in our Phase II CSU study, and we are currently screening patients in our Phase II CIndU study. Slide 16 shows you the design of the CSU trial. We're excited to continue making progress with barzolvolimab. And on -- Slide 17 outlines our upcoming development plans for the upcoming months across disease indications in the chronic urticarias, prurigo nodularis and EoE. Importantly, as we discussed on our year-end call in February, we are well prepared for these activities with the successful development of our subcutaneous formulation, which offers a convenient administration route for patients and physicians. Work is also well under way with our CMO to optimize our scale-up barzolvolimab manufacturing to support late-stage trials as we work towards commercialization. In summary, the data reported today confirm we have a very potent, well-tolerated and active drug candidate for patients suffering from chronic urticarias and other mast-cell-driven diseases. We have observed outstanding clinical activity, including in oma-experienced patients. To date, no other agents have been successful in patients inadequately controlled by oma. In addition to the excellent clinical activity, the favorable safety profile observed in the multi-dose setting affirm our confidence in our ongoing Phase II studies in CSU and CIndU and continue to support our belief that barzolvolimab has a very broad potential across multiple mast-cell-driven diseases. Lastly, we look forward to completing the treatment of the phase in the ongoing Phase Ib CSU and CIndU studies by year-end and reporting data at a medical meeting thereafter. Operator, we are now ready to take questions.

[Operator Instructions] Our first question comes from the line of Yatin Suneja with Guggenheim.

Congrats on excellent data. Just a couple for me, a few on the efficacy and then maybe 1 or 2 on the safety. So first is a clarification question. So the efficacy data that you're showing on the 3-milligram dose, is that before the second dose? We're just trying to get a sense whether you should or whether we should expect any additional benefit with multiple dosing because if you look at the tryptase level, they do try to come -- they are trending up after 6 weeks. So just trying to get a sense of how mature these data might be. And should we see further improvement with second dose?

Sure, Yatin. I'll have Diane answer that question for you.

Yes. So the -- for the 3 milligram per kilogram dose, the efficacy is measured at 8 weeks, and that reflects the single dose. The efficacy was measured before the second dose was given.

And to answer -- this is Tibor. To answer the second part of your question, it remains to be seen, but we do believe we're suppressing tryptase levels quite significantly even with that initial dose. So whether the second dose will just continue that level of suppression or drive it further down, I think that remains to be seen in terms of how that impacts the efficacy scores that we're already seeing.

Got it. And then with regard to the Xolair-experienced patient, can you just talk about like are they refractory patients or how refractory they might be? And then what level of complete relief you might have seen in these patients of these cohort? I do see data on UAS7, but I'm just trying to get a sense of complete relief that these patients saw.

Yes. So the Xolair-experienced patients, the majority of the patients that were in the study had an inadequate response to omalizumab, so either for symptom control or intolerance. And in terms of response, they did achieve complete responses in that group similar to what was seen with the entire group, but those numbers are very small, so we didn't show that data.

Okay. And then one question on the safety side, and maybe if Dr. Maurer can also chime in if he is still available. Can you just talk about these 4 patients? Obviously, you saw them at the lower dose, nothing on the higher dose. I mean, you are all doing a lot of monitoring, which doesn't really happen in clinical practice. So trying to get a sense of how significant these findings might be as it relates to neutropenia that you saw in these 4 patients?

Yes. So there were 4 patients, 2 in each of the lowest dose groups, who had decreased neutrophil counts that were reported as adverse events. All these patients started the study with baseline counts at the lower range of normal, and they had a similar pattern of decrease as we've seen in other barzol-treated patients. One patient had values that never got below 1,500, which actually was the normal range for that patient, but with the grading scale that we applied in the study, it was a grade 1. Two patients had values that dipped below the 1,500 level at isolated time points and we're above that level subsequently. And a single patient dipped below 1,000 at 2 isolated time points and was above 1,000 on subsequent blood draws. There was no pattern of further decrease in counts in any of these patients. All of these were asymptomatic, didn't cause any delays in dosing and returned to normal by the end of the study. And just -- so you know, we did do very intensive hematology monitoring in this study. As a dose-escalation study, the investigators were interested in reporting on value so that they would be commented on by the independent data monitoring committee, which evaluated each dose level and looked at the data. And all this data was reviewed and there were not clinical concerns with the data. Yes, and Dr. Maurer was not able to join us for the Q&A, given the time difference.

And our next question comes from the line of Thomas Smith with SVB Securities.

And let me add my congrats on the early data here. Just maybe one on efficacy. If you could just talk a little bit about some of the concomitant therapies that were used here. I know all the patients were on background H1 antihistamines. But do you know what proportion of patients were on either H2 antihistamines or leukotriene receptor agonist? And do you have a sense of whether this was generally balanced across treatment groups?

So all patients had to be on a background of antihistamine therapies. They had to -- they also could be on leukotriene antagonist, but it had to be a stable dose over the course of the study. I don't have the breakdown of those therapies at this time.

Okay. Got it. And then just on dosing. Obviously, still waiting for the results here from the higher dose cohort. But maybe you could share some updated thoughts on how you think about dosing. Any thoughts to maybe changing the randomization in the Phase II to bias enrollment toward the 150 mg or 300 mg cohorts?

No. I think that the study overall increases our confidence in the doses that we've selected for Phase II. And in Phase II, we do want to look at a range of doses in more patients, so we really get a good idea of the data. And I think we feel very comfortable with the data that we've chosen. But the doses we've chosen, sorry.

Okay. Got it. And then just one other question, I guess, on safety, and appreciate the color that was given on some of the other on-target related AEs, the hair color change, the taste change. It sounded like these occurred relatively infrequently in the study. I guess any additional color you can provide on kind of patient experience? Or were there any patient quality of life metrics that were captured beyond just the urticaria activity scores?

So in terms of the adverse events that were previously reported, infusion reactions and then the KIT related ones that you mentioned, we did have a few cases of those in the study, but they were less than 10%. So that's why they don't appear in the adverse event table.

Any quality measure?

And yes, we did measure -- yes, we've measured other quality of life instruments, but we don't have those data yet. But I mean our feedback is that patients did feel very well on the study and tolerated the drug well.

Tom, we'll have those data once we complete the study in total, and that includes the 4.5 mg. So we'll have most of those data at that point.

And our next question comes from the line of Kristen Kluska with Cantor Fitzgerald.

Let me also add my congratulations on these data. First question I have, I know you don't have any individual patient data, but maybe can you help us better understand the profile and the symptomology of the baseline scores of UAS7 at 30 and even 42 because you had a couple of those? And then what would you view as the meaningfulness on these particular items with the data you saw? And again, just going by the scores and not necessarily the individual patient data.

Sure. Yes. So I think when you look at the demographic data in the study, we were really dealing with a very severe patient population. The UAS7, the mean UAS7 scores ranged from 29.4 to 36.6. And the maximum value that you can have on the UAS7 is 42. And if you look in the ranges, we did have patients that got that high. So these were really highly symptomatic patients. You can also see that by the urticaria control test. So that ranged from 1.3 -- to 1.7 to 3.4. And that score has a maximum of 16. So these are really very -- these are very low values, again, indicating urticaria that's really out of control. So when you're looking at the results that we see, you have to look at it in the context of patients that are very severely impacted by their disease.

And then I wanted to touch on durability. So recognizing it's early, can you make any trends as it relates to the different parameters based off of all patients versus those who were previously on Xolair? And mechanistically, would you expect there to be a difference over time, especially in light of what you've seen through 12 weeks? And I don't know if you can comment for Xolair, but do you have any context still like how long some of these patients had tried the therapy for before they were deemed inadequate responders?

Yes. So in terms of durability, we're -- in this study, we're looking at the first 12 weeks, which is really the treatment period. So you do see with the 1.5 milligram and the 3 milligram per kilogram doses that you get a good response in rates maintained over the treatment period. We'll report on the follow-up period and the durability of this at a later time frame. And in terms of the question you asked about Xolair, the majority of the patients that were -- had previous experience with omalizumab were having inadequate response. They were either intolerant or they were -- they were -- had symptoms despite that. We do have -- we did collect data about that, but we will be analyzing that and presenting it at a later time point.

Again, Kristen, once we disclose the final data after we're done with the 4.5 mg, we'll have that information.

Okay. And my final question is whether you are aware if any of these patients had any comorbidities?

Yes, we captured the comorbidities of patients on the study and that, again, will be something that we'll be looking at and analyzing going forward.

And our next question comes from the line of Sam Slutsky with LifeSci Capital.

Thanks for the update. A couple for me. I guess for patients where you have safety data past the 12 weeks, just curious if it looks any different across parameters from the week 12 time point and so forth, any view there?

So just to comment on it generally, in our adverse event data, we are including all the data from the whole study, so it includes the follow-up periods for the 2 lower dose groups. But really, we -- the only thing I can say is that the hematology values do improve over time, but we didn't have any new signals or anything in particular that emerged in the -- with later follow-up.

Got it. And then I'm curious too if you have any info on just the proportion of patients in the study who had type 2b autoimmune urticaria, which historically doesn't respond as well to Xolair versus other subtypes?

We haven't analyzed that data.

That's the kind of stuff that we drill down towards when we get all the data sound, including the 4.5 mg.

Got it. Understood. And then lastly, just for me, remind me, what's the potential timing for when we might see the next update from other cohorts and just on the follow-up?

Yes. So we're planning to have all the patients enrolled for the 4.5 milligram per kilogram and then do an analysis of all the data, and probably we'll do that by the end of the year or early next year.

Yes. We'd like to present it at a medical meeting, if we can, Sam. So it will be around those time points. So if there's something at the end of the year or more likely at quart AIS, then we would present those data.

And our next question comes from the line of Joe Pantginis with H.C. Wainwright.

Great data. So not to belabor this point, but I'm just curious about a couple of things. I appreciate all the great details you give Diane about the neutropenia. So -- and you said the patients were symptomatic, didn't require anything. So curious, the process that you went through to identify, say, the UTI patient or patients as unrelated?

Well, that -- so the -- there was a single patient who had a report of neutropenia that also had a UTI. And as you can see from the adverse event table, UTIs are really quite common in this study with the same rate in placebo as in the treated patients. And the investigator made the attribution that the UTI was not related to the barzolvolimab and it was similar in character to the other UTIs that we saw in the other patients, which were just very routine and treated with a course of antibiotics.

Right. It is somewhat common in this age group.

Yes. And this is mostly female, middle-aged population where UTIs are quite common.

I appreciate that. And then I know this kind of question has been asked on prior conference calls around barzo's data releases. But when you look at the potential tryptase impacts to consider that have might -- let me rephrase. When you look at the potential tryptase impacts that you're seeing and there are very dramatic reductions with these doses, what is the other potential that you would consider for other, say, phenotypic effects beyond mast cell impacts, if any?

Tibor?

Yes. I'm not exactly sure I understand where you're going with that, Joe. I mean, I think the tryptase data we have from these cohorts is pretty much what we predicted based on our earlier subjects of...

Yes, Tibor, no, I'm sorry. So let me rephrase. So instead of like the tryptase levels, the impact that it has on reduction of mast cells and any potential clinical impacts that might be not foreseen at this point, but maybe could come out?

I see. Well, I think the data suggests that -- to have the optimal clinical effect, we really do need to reduce tryptase levels to near or below detectable levels. And we've shown previously that does correlate with a very significant reduction in mast cells in the skin. There are hypothetical potential concerns about longer-term mast cell depletion. We haven't seen any evidence that, that's something of concern for us, and we will continue to monitor that. But to date, we think that, that's still the best approach to really controlling these mast-cell-driven diseases.

Got it. And I guess for Anthony and the company, when you look at -- it's very nice to see the oma experience data that you have in the poster, and I guess, pretty forward-looking question here. But how may this impact both your pivotal plans and also your initial target market population?

Well, I think what it does is it allows us to be agnostic about the population that we bring into these studies, whether they be naive or experienced or refractory. So hopefully, that broad ability to recruit those types of patients will make those studies go quicker, be more amenable to investigators. And certainly, if these data hold up here, obviously, it's a larger market that this drug will address than the others. So that's all a positive.

[Operator Instructions] And our next question is going to come from the line of Chris Howerton with Jefferies.

I'll also offer my congratulations. Really appreciate all the details. I think most of everything I would have wanted to ask has already been asked. Tangential to this readout, we have also been getting questions from investors around potential for reproductive aberrations with KIT inhibitions. So I guess, can you tell us when the preclinical reproductive toxicology studies will read out and we'll learn more about that?

Chris, this is Tibor. Yes, certainly, we have some data that speaks to that based on what we've recently reported from our 6-month chronic tox study that was done in mature animals. And thus far, we are very pleased to see the outcome of that, particularly without any evidence of impact on female reproductive organs. There are, of course, additional toxicology studies the agency will be looking for that look at pre- and post-natal development in animals as well as juvenile toxicology studies. So we're in the process of doing the analysis for those additional studies, working with the CROs to get those set up. It may be some time yet before we have data from those studies, but we are obviously performing all the studies required for these types of programs by the FDA.

Thank you. And there are no other questions in the queue, I'd like to turn the call back over to Anthony Marucci for any further remarks.

Thank you very much, and thank you to everyone for joining us this evening. As you can tell, we're very excited and look forward to providing further updates as soon as we possibly can as well as on the other studies throughout the year. So we wish everybody a great night, and a happy 4th of July weekend.

This concludes today's conference call. Thank you for participating. You may now disconnect. Everyone, have a great evening.