Hi, good afternoon, everybody. Thank you for joining us for our barzol phase I-B multi-ascending dose CSU update study results that were presented this morning at a poster here at Claud AI. Just to give you a format of the meeting, I'm gonna ask Diane Young, our Chief Medical Officer, to come up and to discuss the results of the study, then we'll ask Dr. Maurer to come up and make some comments. Dr. Maurer has a prior obligation, he needs to be out of here by 5:00 P.M., I just wanna be cognizant of his time there as well. I also wanna thank the people that are joining us today via the webcast. Having said that, we're gonna make some, you know, communication of some forward-looking statements today. I ask you guys to refer to our SEC documents, which discusses our forward-looking statements or risks and everything in those documents. With that, as I said, the agenda's going to be the phase 1-B study. Dr. Maurer here is with us and here to answer some questions at the end of the day. We also have on the table in front here with us is Dr. Tibor Keler, who is Co-Founder and Chief Scientific Officer of the company, as well as Diane, who is our Senior VP and Chief Medical Officer. With that, I'll ask Diane to go through the data. Mic on? Okay, good. Thank you. Thanks, Anthony. I'm very happy to be here today, I just wanna start off by introducing Dr. Maurer, who really needs no introduction. We're so happy he's able to join us today. He's the Professor of Dermatology and Allergy and Head of Dermatologic Allergology at Charité – University Berlin, and he also coordinates the Global Allergy Networks of Urticaria and Angioedema Reference and Centers of Excellence. He is deeply committed to the study of urticaria, both in the clinic and in the laboratory. He has participated in more than 60 clinical trials, including the phase 1-B and phase II trials from Celldex Therapeutics. We look forward to your perspective after going over the data. I'm really happy to summarize the results from the phase I-B multiple ascending dose of barzolvolimab in CSU patients, which were presented earlier today. In the study, we saw rapid, profound, and durable symptom improvement in patients with moderate to severe CSU refractory to antihistamines, including in patients with prior OMA experience, and we observed clinical activity in multiple dose cohorts. barzolvolimab was well-tolerated with a favorable safety profile showing, you know, consistent results with what we've seen in our previous single-dose studies. We believe that barzolvolimab 's unique mechanism of action as a mast cell depleting agent has broad potential in mast cell-driven diseases. We believe that these data support our ongoing phase II studies in chronic inducible urticaria and CSU. We announced today that we are expecting to complete enrollment in the phase II CSU study by the end of third quarter and report top-line data in late fourth quarter or first quarter of 2024. As Dr. Maurer will much more eloquently than me describe, chronic spontaneous urticaria is a disease which is driven by mast cells. It's extremely debilitating disease which impacts all aspects of a patient's life. It is currently treated with antihistamines, and omalizumab is the only approved biologic for the 50% who don't respond to antihistamines. There is a great need for new therapies. This is the study design. You're all familiar, I believe, with the design. It's a multiple ascending dose study looking at four dose regimens and placebo, and all doses were given intravenously in this study. Patients received either three doses of 0.5 or 1.5 mg/kg given four weeks apart or 3 mg or 4.5 mg/kg given eight weeks apart. Then they were followed out to 24 weeks. The primary objective of the study was safety, and the primary endpoint for clinical activity was the mean change in Urticaria Activity Score 7 at 12 weeks. We presented interim results from this study at EAACI last year, and at that time, we presented data out to 12 weeks for the two lowest cohorts and data out to eight weeks for the 3 mg/kg cohort. For this poster and at the time of the data cutoff, all three lower dose cohorts had completed 24 weeks, and all patients in the 4.5 mg/kg cohort were through the 12-week treatment period. We were able to show data out to 20 weeks for this cohort because at that point, data from six of nine patients was available. We thought that was enough to, you know, begin to look at the results. These are the demographics and baseline characteristics. The patient population had moderate to severe chronic spontaneous urticaria with UAS7s around 30 and UCT around three, which indicates poorly controlled disease. Patients had CSU for a long time in this study, more than five years on average. All patients were refractory to antihistamines, 37% of the barzolvolimab -treated patients had prior omalizumab. The majority of these patients had an inadequate response to omalizumab, which was defined as patients who had persistent symptoms despite omalizumab and patients who were intolerant of omalizumab. We'll talk more about that later. T his is the activity shown by Urticaria Activity Score 7. This is the primary activity measure in the study, the barzolvolimab -treated patients had rapid and durable improvements in Urticaria Activity Score 7, with the most profound and durable effects being seen at the three highest dose groups. We know from the tryptase data that these are doses at which KIT receptor appears to be saturated. As a reminder, the 1.5 mg and mg/kg doses given intravenously correspond to the 150 mg and 300 mg doses that we are giving subcutaneously in our phase II studies. Another notable thing about this data is how long the symptom improvement lasted in these three highest dose groups. Patients still had reductions even at 24 weeks, which is 16 weeks after the last treatment that they received. This shows the ISS7 and the HSS7, which are the two components that make up the UAS7, specifically for itch and hives. You can see a similar pattern of rapid and durable improvement when looking at these two, these two components. The most important thing to patients is really complete relief of symptoms, which is Urticaria Activity Score 7 equals to zero or complete response. The majority of patients treated at doses greater than or equal to 1.5 mg/kg achieved complete response by week 12, is 57% for the 1.5 mg/kg group, 44% for the 3 mg/kg group, and 67% for the 4.5 mg/kg group. To provide context, omalizumab has a complete response rate of 36% in their prescribing information. Once again, the duration of complete responses is very impressive. Seven of eight patients who had been treated with barzolvolimab at 1.5 mg/kg or 3 mg/kg and had a complete response at week 12, maintained their complete response through the 24 weeks. Another measure of activity is the Urticaria Control Test, which really measures symptoms and how well the disease is controlled and the patient's general quality of life and looks back at four weeks, the previous four weeks. UCT is validated for both CSU and CIndU. With this, UCT greater than or equal to 12 is considered well-controlled disease, and UCT equal to 16 is considered complete control. On the left, we see the mean change in UCT scores over time, and on the right, we see the% of patients who achieved UCT greater than or equal to 12 over time. More than 60% of patients achieved well-controlled disease by 12 weeks, which again persisted through the follow-up period. It was interesting to us that patients in this study started with a lower UCT than in our previous CIndU study, but the magnitude of increase in UCT was roughly similar. It was kind of interesting. This chart shows the pooled results from the three highest dose groups comparing omalizumab-naive patients, shown in black, to omalizumab-experienced patients, shown in orange, looking at UAS7 on the left and UCT on the right. This is a really nice way of showing that the pattern of response is really identical between the omalizumab-naive and the omalizumab-experienced patients. 19 patients in the study had prior treatment with omalizumab, and 11 of the 19 were considered OMA-refractory, which I gave the definition before. Most of them had symptoms despite being on, you know, an adequate trial of omalizumab. Of this patient population that we're looking, which is the pooled group of 1.5, 3.0, and 4.5, there were five of these that were OMA-refractory, and four out of five had complete responses by UAS7. You know, really the OMA-refractory, again, subsets of patients, but, you know, are having responses similar to the oma-naive and to the, you know, oma-experienced in general. This shows the pharmacokinetics and serum tryptase. Consistent with our previous studies, tryptase suppression paralleled symptom improvement, and this demonstrates the impact of mast cell depletion on CSU disease activity. Tryptase has really been a remarkable biomarker for the program. It just is consistent from study to study. This is looking at the safety. Barzolvolimab administered with multiple intravenous infusions was well-tolerated. Most adverse events were mild or moderate and resolved while on study. The most common adverse events were hair color changes, COVID-19, headache, and neutropenia. COVID and urinary tract infections were all considered unrelated to barzolvolimab. This shows the hematology parameters. These are really consistent with what we have seen across our studies. We have not seen a pattern of further decrease of hematologic parameters with multiple doses. We saw transient asymptomatic neutrophil decreases as adverse events for five patients. Four of these were previously reported in the EAACI presentation. The new patient had an isolated value between 1,000 and 1,500 cells, which was above 1,500 on the next determination. You know, we're very excited about these data. We believe that the magnitude and durability of symptom improvement and the observed safety profile support our ongoing phase II studies of barzolvolimab in CSU and CIndU. This slide shows the design of the phase II study in CSU. The study's been ongoing since June, and as I said before, we now expect to complete accrual in this study by the end of third quarter and report top-line data late 2023 or first quarter 2024. We are all really looking forward to that. Now I would like to turn this over to Dr. Maurer to provide his perspective on the study results, and then we will open it up to your questions. Thank you very much. Look, we're very happy with these outcomes. Obviously, this is the best we've ever done in chronic spontaneous urticaria when it comes to the treatment. It's a disease that really is devastating and underestimated in its impact. To see what barzolvolimab can do in this patient population, which was a severe chronic spontaneous urticaria population, including patients who failed the only second-line treatment, is remarkable. Gives us a lot of hope that we'll be able to do a lot better once we have this in our hands. There's a couple of things here that are very interesting that I want to highlight. Clearly, the dose response and the difference also between what we see in CSU and CIndU. I think that deserves some comments. Let me touch on the first one first. We've seen across the three doses some variability. This is not unusual for chronic spontaneous urticaria. It's a much more fluctuating disease that than, for example, CIndU. To see that one time point, you have something that's a little bit out of the curve is not unusual. That's to be expected. To see the dose response, especially between the lowest dose and the three higher doses, gave us new insight on what barzolvolimab really does. We continue to believe that this is a mast cell depleter, and this is why it works so well. You have to answer the question, why do you see this effect, the blue line? No. Remember the blue one that goes whoop, whoop. We actually call it the whoop effect. That term was coined when we first looked at the low-dose response to omalizumab, where patients who were on four week treatment intervals right before the next injection, the last week wasn't so good. They also went whoop, whoop and had that pattern. We're not, you know, barzol is not Oma by no way. You know, we're looking at a very different MOA. At least when we see that primary MOA as in mast cell depletion. What's going on in the low dose, and how can we interpret that? My interpretation, and I may be wrong, more data may be needed, is that at a low dose, barzol doesn't kill the mast cells, but it still impacts mast cells. I'm from a therapeutic point of view, that's not so remarkable. From a biological point of view, that is really remarkable because it shows us that KIT is such an important receptor that beyond keeping mast cells alive, also regulates their activity. Because this happens early on, it may be something that contributes even at higher doses, where you would assume that why wouldn't it happen at a higher dose when it happens at a lower dose, may contribute to these to this very fast onset of action that we see. This I find from a mast cell biologist's point of view, very interesting. KIT biology is poorly understood, and barzol will clearly help us to understand this better. Maybe from a clinical and patient point of view, the comparison between CIndU and CSU is important. We know that many patients have both, and this is another interesting and important point because we know that patients with CSU who also have CIndU can have different treatment responses to treatments other than barzolvolimab. In the future, we for sure will look at patients who have two or more chronic inducible urticarias. Now, the CIndU data to you may appear as black and white, and it is. This rate of complete response is unrivaled. You can't do better than 100% complete responders, right? We all agree on that. We do get complete response in 100% of the high-dose CSU patients, as I predicted. Told you so. No, just kidding. It wasn't as clear in CSU as it was in CIndU. Why? Because we're dealing with a disease that is not as clear-cut and mono-linear as CIndU. CIndU, you have the trigger. The trigger annoys the mast cells. The mast cell degranulate. It causes the signs and symptoms. The wheals come, the wheals stop, and you're back to square one. You don't have a chronic inflammatory response, an increased susceptibility of the tissue to respond to the next trigger. The next trigger needs to be exactly the same strength in order to produce a signal. This is very different in chronic spontaneous urticaria. We're starting to see infiltrates that you do not see in CIndU. You do not see a lot of eosinophils, neutrophils, T-cells move to the wheals in CIndU. But you do in chronic spontaneous urticaria. What this does is it contributes to the wheal that is emerging, but they linger. Eosinophils can be seen in non-lesional skin in chronic spontaneous urticaria, which is post-lesional or pre-lesional skin. In other words, what mast cells do in CSU results in effects that are different than in CIndU, and that could have made it more difficult to treat chronic spontaneous urticaria. To some extent, you see that, no, we see a complete response to a lower dose of barzolvolimab in CIndU. No, we half the dose, and we still see 100% complete response. We need the higher doses in CSU, at least when we look at the first 24 weeks, to get to that complete response rate that we know from the CIndUs. Do I think that we need these high doses moving forward? I'm speculating here. No off script. This is just my thought on this. I don't think so because once we've done the job of reducing these mast cell numbers, which tend to be higher than in CIndU, which tend to have downstream effects that need to normalize before we come to a normal skin as we have it in CIndU when there's no lesion. That needs maybe a hit in the beginning, and it needs some time for things to normalize. Then all you need to do, just like in CIndU, is keep these mast cells gone. It'll be interesting to figure out, and this is not something that we are, we now have to solve, but it could very well be that, by looking at a, looking closer at the response to the treatment over time, we may have a dynamic treatment in these patients. Of course, we all think about how can we make this drug even safer? How can we reduce the, or improve the tolerability of the drug, just like we've done for CIndU, where we can half by halving the dose, the rate of side effects, and maintain complete response. I think there's still room for this in chronic spontaneous urticaria. For now, I'm very happy to say that and see that what we thought before we started this study is true. Chronic spontaneous urticaria is a mast cell-dependent disease. It is critically dependent on mast cells. When you take them out, CSU stops. This is really proof of concept that was necessary, needed, not unexpected, and clinically very, very meaningful for patients who struggle with this devastating disease. Thank you, Dr. Maurer. We appreciate your thoughts on the subject matter. As promised, we're opening it up for questions, realizing that Dr. Maurer needs to be done here by five. Fire away. Kristen. Hi, Kristen. Would you say that the omalizumab variance data is consistent separating those who are refractory versus those who had some level of response? How about amongst the different doses? By anyone. I mean, I'll just I can start and then yeah. I think because of the way we enrolled the study, we really can't distinguish among doses 'cause it's just a few patients in each dose. That's why I lumped those doses together. You know, I think that clearly the trend in those omalizumab-refractory patients is with a high response rate, you know, as with the total population. Dr. Maurer can probably talk about why that's such an important thing. I mean, of course it's important when you only have two treatment options, and you show that another treatment works in patients who failed both of them. You know, that's a big relief moving forward because now we know that we can do better than omalizumab. I'd be cautious though, because the fact that Barzol works in Oma non-responders, which is clear from this data, argues that it's a more overarching mechanism where you don't need to block individual pathways of mast cell activation. It just doesn't matter to barzol how these mast cells were activated. You just knock them out and that does the job. When you look at the way we did the study, then you have to acknowledge that there's not as rigid, rigorous, I should say, rigorous assessment of the response to omalizumab, previous response to omalizumab, as you would do if this were assessed prospectively. You know, in the future, what can we do? We can go against oma. No fear here. No. That would settle that once and for all. We could really include patients where we have UCT data, UAS data on the previous omalizumab experience. That includes patients because that happens today, patients who receive higher than standard doses of omalizumab. I think this is something that we should explore moving forward so that we can be even more confident that this is what happens. For now, I think what's fair to say is that barzol works where oma doesn't, and that's about as much color as we have on the topic. Thank you. With 24-week data on hand now, how do these findings set your expectations for the ongoing phase II trial? Can you detail some further advantages you see with things like exposure and other factors now that you're using subcu? Yeah. Yes. Okay, we can speculate. I love to speculate. That's nice. I believe that the subcu dose will work as well as the IV. I think also that the rate of, well, there will be no infusion reactions, not that there were many in the IV, but that's a clear benefit patients like that. We'll make it fit for use self-administration. Now, that's the ultimate goal, and that's what will happen. This is how we will move forward. There's a clear benefit in moving to subcu. Other than that, it's early days. No, we've just started with this study, so we'll see how it works out. I can tell you that in the long run, we'll be interested in long-term data, both on can we maintain that clinical response, can we steer patients through difficult times which may come in terms of trigger exposure, you know. Only when you go, let's say, for 52 weeks, will you have that fall period where viral infections tend to happen, or will you have that aspirin that patients take, although they shouldn't. You know, these triggers that we know from daily life make patients have exacerbations. That's why we were very interested in the long-term data. You know, the longer we treat, the more often we treat, the more confident we become that this is really something that we will continue to see moving forward. I remember the discussions that we had when we only had single-dose treatment. What will happen to these Will it get worse if we treat, you know, things that we talked about? Will that get worse as we move forward? I said then, "I don't think so." It didn't get worse by treating longer. Yes, we need those safety data moving forward, and we will get a longer exposure with the trials that are ongoing. In the long run, we will need treatment that we can give for many years in these patients before they lose the disease by themselves. Hi, I'm Daniel from Guggenheim. I have two questions. First on dosing in a maintenance phase. So far the durability looks great. I'm interested to hear your perspective on thinking about maintenance dosing. Would you think patients will be taking barzol every other month, or is there an opportunity for patients to take fewer doses over the course of a year? Yeah, that's a great question. Given what we know today, I don't think that you need to give it every four weeks. When you kill a mast cell, you really need to make sure it's dead, then it will stay gone. In other words, I think of barzol as we shoot them, that's it, you know. Then they need to bring new precursors back to make new mast cells to become mature, to become reactive again. We don't need to keep hitting the system when there are no mast cells yet. I think that's true benefit because patients, when you think about it, are happy to inject every eight weeks rather than every four weeks. Probably happier to inject every 12 weeks than every eight weeks, you know. I think this is a true benefit that the mechanism of action of this approach rides on mast cell biology. We know that the skin mast cells that drive the disease, that they are, well, they are very expensive to make for the host, you know. It takes a long time before we see these precursors come into the skin, start to mature, and then become reactive. We have to understand that a little bit better, because right now we have on the relapse data only matching mast cell data for the CIndU study. It looks like, you know, we have weeks and weeks and weeks, if not month, of absence or low levels of mast cells that will not allow for signs and symptoms to occur. Of course, the, you know, there's huge benefit. Can we push the envelope? Can we bring these patients to 12-week interval injections? I do believe it's possible. I don't... Short answer is we will be able to treat less often than every four weeks, I predict. Got it. The second question. It looks like in the three main groups there were two late responders. I'm just interested to know, you know, what is going on there from a mechanism perspective? Very good question. I don't know, but I'll be happy to speculate. Remember, he's speculating. We don't. Yeah. No. I love to speculate. Look, we know that some patients with chronic spontaneous urticaria have increased mast cell numbers. We don't know what that means, and it's not consistent across studies or across patients. The fact that it is possible, that it has been shown that individual patients have double, if not triple the number of mast cells in the skin means you're going against double, if not triple the number of enemies. That could be something that requires longer exposure or repeated exposure in order to get them down. Whereas in CIndU, it's very predictable. You know, they have as many mast cells as we do always. That's not the case in CSU. That's a simple explanation that is testable, and I'd love to see if it's true. Thanks. Thanks. Thomas Smith, SVB Securities. Thank you guys so much for this webinar. Just, I was wondering if you could provide a little additional color on the use of rescue therapy in the study, and talk about the differences between the active and placebo groups. Can I ask you guys to repeat the question? I think probably the audio on the Q&A. The question is if we can talk about rescue medications on the study, particularly in the placebo group, correct? Yeah. We haven't, you know. We have a lot of data from the study on rescue medications in terms of antihistamine rescue medications, which we have to analyze. One of the things that we looked at was, you know, we looked through all the things that they had gotten, and there is a patient in the placebo group that got omalizumab and steroids, and they actually should have gone off the study, but they stayed on the study, and they had a response. That actually, mess, you know, affects the placebo curve in the study. That's the biggest issue that we've identified so far with rescue meds. Mm-hmm. You know, we will be looking at rescue med data. It's quite complicated because the patients take, you know, they take antihistamines on it. They have to be taking them, and then they take them for rescue. You really have to do a very careful analysis. With the small number of patients, it might be hard to see the whole pattern, but, you know, we're gonna look at that. In general, this is a minor point of concern, if at all. Rescue medication never affected the trial to the extent that you would have another outcome without it. We tend to overestimate the contamination by rescue medication, but we have to understand that these are short-acting antihistamines that are only taken on the day when they are needed. There's little wash over, and patients are instructed to take the rescue medication when the symptoms get so worse that they're unbearable. In other words, they will document their disease activity as high on that day that they take their rescue medication. They will take it. They will have six hours, eight hours of relief. Next day is a new day. Even though they take the rescue medication, it will not have contaminated the daily score or the washover score or the score of the next day. It really seems like we're doing, you know, like we're adding treatment to them, but not in the way we assess the disease activity the way we do. Thanks. Sam Slutsky, LifeSci Capital. Thanks for the questions, and congrats on the data. A couple from me. Just to build on Evan's point, in the data presented, it looks like efficacy continues to go down over time. Given the kinetics of mast cell depletion, greater number in CSU, and then the removal of these other immune cells that get attracted, is there potential for efficacy to keep improving as we go out? That's, I mean, that's what we're gonna try to find with even longer chronic treatment. I mean, you know, it definitely is going up during the 12 weeks. I don't know if you have any- They let me speculate. I love to do that. Look, you're probably going into system with increased mast cell numbers, other inflammatory markers that you need to normalize before you come to where you are in SYNDGU from the get-go. The idea that you keep treating these patients, which is what we will do, is treating these patients when they're at a different point, you know. When you treat the second time, you already have less mast cells as when you treated the first time. I think the idea that the response will continue to improve or that you may even have longer intervals or lower doses needed to maintain that response is something very attractive and could be explored. I think it would then be explained by changing the baseline, and reducing, by those first hits, the systemic inflammation that is there, which you no longer have once you do it a second, third, fourth time. For Celldex Therapeutics, just on the receptor saturation, remind me what that looks like between the 1.5, 3, and 4.5 mg/kg group, and then the translation of that into the subQ dose that's being used? Yeah. I'm not sure if this is on, but with regards to saturation, we've seen that those dose levels lead to the same level of stem cell factor accumulation in the blood. That indicates to us that we've had hit a similar level of saturation, whether it's the 1.5, now that's given every four weeks, or the 3 mg or 4.5 mg. I think, as we've discussed on many occasions, you know, we think once you're at saturation, it's really more about the length of exposure you get from that particular dose. That's how we would expect to be able to think about regimens that are perhaps given less frequently. Subcutaneously, we've shown in our healthy volunteer study that the 300 mg flat dose gave very similar pharmacokinetic profile and tryptase reduction profiles as seen with the 3 mg/kg IV formulation, and similarly for the 150 compared to 1.5. Our expectation is with the different regimens we have in our subcu phase II study, we're also hitting saturation for the majority of patients, either with the four week 150 flat dose regimen or the 300 every eight week. Just lastly, real quick, on the placebo patient who got rescue omalizumab and responded, was that a complete response they had, or what kind of response? Yeah, they had a complete response. Okay. It was very transient complete response. They were antihistamine refractory, so they were never exposed to OMA. All right. Thomas Smith at SV Securities. Try this again. Could you just provide or maybe comment on the immunogenicity that you're seeing in the study to date, and I guess your expectations for the as you move to the subcue form? Right. We have seen some ADA to the antibody. Given in the IV as we've reported here, we're really pleased to see that it's had absolutely no impact on the exposure levels. The pharmacokinetics, even at the lowest doses, are actually even better than what we had expected based on single-dose treatment. This is perhaps because we've removed the sink, the target, and, you know, the subsequent doses are really lasting a long time. We have yet to address the longer-term question about ADA response, particularly with the subcu dosing. I think we'll be able to answer that question with the phase II studies. So far, the ADA that we've seen has certainly not impacted pharmacokinetics or clinical activity. Okay, great. Yeah, I appreciate that color. Maybe one for Dr. Maurer. If I could just ask you to, maybe contextualize the omalizumab experienced patients in this study versus some of the other contemporary phase II or phase III studies, for other agents like remdesivir or dupilumab? Yeah. I'd rather not, because we have not a lot of information on the OMA experience of these different patient populations in the different trials. Sometimes they're called OMA experience, sometimes they're called OMA failures. That is again, because this is a retrospective look at the patients who went into the trial. Sometimes chart data available, sometimes physician global assessment of what that previous omalizumab experience was like, without details on how long have they had OMA, what other medication did they have, what was the dose, what was the actual response? Was this a partial response? Was it a complete non-response? Was it a mix between did not tolerate and didn't respond well enough? This time I don't speculate because there's just not enough data to say that based on these different OMA experienced populations, including OMA failures, we conclude that there's a difference in the follow-up treatment in these phase II studies and phase III studies now. Yeah. I mean, like you said, it goes for Dupixent, it goes for Remy, it goes for barzol. I think we need more information on these patients as they go into the trial or a true head-to-head or prospective assessment of their OMA experience to really be able to compare different treatments for their effects in these OMA experienced populations. Understood. Thanks. I have a question coming in from, Roger Song with Jefferies, who wants to know if there's a dose-dependent drop in neutrophils observed and what the differences were in the baseline neutrophil levels in the treatment groups. The, for the three doses that, you know, we call the saturating doses, very similar you know, change in neutrophils, but the 4.5 mg/kg group had a lower, slightly lower baseline than the others. It looks lower on the chart, but if you look at the baseline, it's a bit lower than the others. Any other questions in the room? This is for Dr. Maurer. Could you just discuss all the places where barzol's profile could fit? I know it's still early days, but as we think about, you know, antihistamine refractory, post-Xolair, post-Dupixent, kinda how it could play in each of those roles. Sure, Sam. I think that barzol will work in all diseases where mast cells contribute to the pathogenesis, and that's a long, long list. You have to differentiate between diseases that are critically mast cell-driven. Now we know that chronic urticaria across all the different types of urticaria and phenotypes is such a mast cell-driven disease. The other two diseases that we really need to look at, and we're in the process of wrapping our head around this, because they are mast cell-dependent, mast cell critically dependent diseases, mastocytosis and MCAS, holding huge potential, from my point of view. These diseases must respond. Must. Because they are... We wouldn't have these diseases as humans if we had no mast cells. That's the smallest part of where Barzol, or the sp... In terms of numbers, that's a really low number in terms of patients overall who could benefit from barzolvolimab. The next tier is diseases where we know that mast cells play a role. We're not sure how important they are, but we think that they are very important. These include all the type one allergen and type two inflammatory diseases, from anaphylaxis to food allergy, to asthma, to allergic rhinitis, to chronic sinusitis with nasal polyps, to all of these IgE type two inflammatory diseases where mast cells are known to be increased, be activated. There's a correlation between mast cell activation and disease activity, so very strong circumstantial evidence that mast cells contribute to the disease. Here you may see some diseases where 60% or 80% of patients, depending on their endotype, will be complete responders, just like in chronic urticaria. The other two, 20%, may not be complete responders, may be partial responders because they have a different endotype. I'm thinking asthma here, where we clearly know that there are different endotypes where the role of mast cells in terms of contributing to the pathogenesis may be different between different patient populations with the same disease. There are other diseases where we can have fun speculating. You know, you and I, we talked about the long list of diseases that are out there. With pemphigoid, we just mentioned must respond. I think that rheumatoid arthritis must respond. I think that the chronic inflammatory intestinal diseases will respond, IBD and Crohn's. Mast cells are professional troublemakers when it comes to inflammation. Any chronic inflammatory disease you have to have, you have to at least be ready to see that kicking mast cells out will improve it. The caveat is that mast cells can be bystanders. I haven't seen a single disease yet where they are only bystanders, where they're not in some kind of feedback loop, add to the trouble that's there. It is possible. It is theoretically possible that a disease where you see increased numbers of mast cells, maybe even increased rates of mast cell degranulation, when you knock them out, it'll change nothing about the clinical, the clinical profile, but it's highly unlikely. If I had to guess how many diseases will respond to OMA, it's somewhere between 30 and 75. It's that high. That's a huge population, with varying degrees, obviously. That's where it gets really interesting, because we will not only be able to help patients who we currently can't help, but we will also learn about where mast cells play a role and then further down the road, how they do it. That's where the scientific merits of this approach are great. Evan from Guggenheim again. Two more questions. First, now that you've narrowed guidance for the phase II CSU study, where does CIndU fall in relative to CSU? Yeah, one at a time, Evan. We're guiding on the CSU. We have a better handle on that. We think CIndU will be sometime in 2024, we'll probably give an update on that mid-year. We'll have a better handle on that since it started a little bit later. Got it. Got it. Thank you. Then one more for me. In terms of EoE, Dr. Maurer, you mentioned there are numerous diseases where mast cells are playing a role. EoE is in there. Exactly. I'll group that in there. I forgot chronic prurigo. That's a sure bet. Chronic prurigo will work. There's just too many. If you know, if the guidance is whenever you see IgE be a driver, 'cause that IgE does that through mast cells, that's one argument that. There's other diseases outside of these classic type two inflammatory conditions and IgE-driven diseases. EoE, there's still a little bit of need to better understand the pathogenesis and the differential role of eosinophils versus mast cells. Look, eosinophils are not born in the esophagus or the skin or the gut or the airways. They are blood cells, and someone needs to tell them where to go, and no one does it better than mast cells. If you annoy a mast cell just hard and long enough, they will call eosinophils 'cause they think you're a parasite and they will want to fight you together. They are buddies in crime when it comes to diseases, just like they're Batman and Robin when it comes to fighting parasites. They are an effector unit where the mast cells love to call them for help when they can't do the job alone. That's why I think it's a good target. Mast cells are a good target for EoE. Down the road, we will figure out just how many patients and how well they will respond from mast cell depletion. Got it. Thank you. With that context, where are you in preparation for the EoE study? Yes. We're still guiding phase, first half of the year, and that's when we plan on starting the study. Got it. Thank you. Thomas Smith, SVB. Maybe just kind of following up on that. Now that you've laid out sort of timelines for the phase II CSU timing, if we kinda play that forward, how quickly do we think we could turn around into a potentially registrational study and what are the current thoughts around whether or not you would want to or need to go head to head versus OMA? You wanna talk about the head to head? Head to head, for regulatory purposes, we don't think that we would have to go head to head. You know, we may have to do it for other reasons, you know, for in some way, you know, because of pricing and things like that. You know, we're as far as starting phase III, we're certainly gonna plan as quickly as we can and get it started as fast as we can. It'll definitely be in 2024, Tom. The exact month, I can't tell you at this point, but it'll be in 2024. Got it. That's helpful. Thank you. Yep. Any other questions? Okay, Anthony, I'll turn it over to you to close. Okay. Well, thank you, everybody, for joining us. Dr. Maurer, thank you for joining us. I know you've been extremely busy. We thank you for your comments and your speculations, as you like to say. Everybody here joining us in person, I appreciate you guys coming and for your time and as well for those that joined us on the webcast today. We appreciate you guys taking your Sunday afternoon and listening to our presentation. With that, we look forward to updating everybody going forward. I'm sure we'll have conversations with all our investors and we'll keep everything up to date. Thank you.