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Good day, and thank you for standing by. Welcome to the Celldex Therapeutics webcast. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star-1-1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1-1 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Sarah Kavanaugh. please go ahead. Thank you. Good morning and thank you for joining us. We're very excited to start our day discussing positive top line results from our two phase three studies in chronic spontaneous urticaria, Embark CSU1 and Embark PSU2. In addition to being available in the webcast portal, the accompanying slides for this morning's call are also on the investor relations page of our website in the events section. Joining me on the call this morning are Anthony Marucci, co-founder, president, and chief executive officer, Dr. Tibor Keller, co-founders, executive vice president, chief scientific officer, Doctor Diane Young, senior vice president and chief medical officer, Terry Lauber, senior vice president and chief commercial officer, doctor Margo Chiozzi, senior vice president of regulatory affairs and quality, and Doctor Diego Alvarado, vice president of research. Before we begin our discussion on this top line data, I would like to direct your attention slide two with respect to important information regarding the forward-looking statements that today's speakers will be making. We will hold a question and answer period after the presentation of the data. I would also like to note that these are very large studies encompassing almost 2,000 treated patients, and we received results very recently. The team has worked very hard to analyze the key data, and you will find today's discussion fulsome. That said, we are continuing to review data, and there will likely be questions we are unable to answer at this time. We look forward to presenting the full 24-week data set, which we intend to submit for presentation to the American Academy of Allergy, Asthma, and Immunology Annual Meeting in February. With that, we will now advance to slide three, and I will turn the call over to Anthony. Anthony Acciavatti, Thank you, Sarah, and good morning, everyone. For decades, we have seen well-controlled disease accepted as an adequate outcome in CSU. Today, we are incredibly pleased to share Phase III top-line data that clearly demonstrate that barzavolumab can do better for patients. Turning to slide four, the data we are going to share with you this morning deliver on barzovolumabs' potential to be a transformational therapy for patients with CSU. Once again, this time across two studies comprising of nearly 2,000 patients from more than 500 sites in 43 countries. The primary endpoint and all key secondary endpoints have been met at both barzavolumab dose levels. Across each endpoint, the data are clinically meaningful and demonstrate highly statistical significant decreases in disease activity. We are seeing rapid, profound, and durable efficacy that is best in disease in CSU. This deep efficacy continues to be clearly demonstrated in patients with the highest level of disease burden, severe disease that is refractory to omalizumab, and CSU that presents with severe angioedema, uniquely positioning and differentiating barcobal map. While we are primarily going to show you efficacy at 12 weeks today, we saw in Phase 2 these effects are sustained or deepened from Week 12 to Week 24 across all primary and key secondary endpoints. Our overall safety profile through the 24 weeks also remains consistent with our Phase II experience, now in a much larger, diverse patient population. We have dosed about 2,400 patients with subcutaneous barzavolumab across our Phase II and Phase III reported studies, delivering more than 11,000 individual doses of either barzovolumat 150 or 300 milligrams in our Phase III studies alone to date. Our large Phase III experience reinforces that barzavolumab has a predictable, consistent, well-tolerated safety profile that we believe results in a favorable benefit-to-risk profile that will support barzovolumabs' broad use across CSU. We couldn't be more excited about these data and what it means for patients and physicians. remind you on slide 5 CSU is a miserable disease that affects 1.8 million people in the US alone these people experience relentless unpredictable hives itch and disfiguring swelling that affects all aspects of their lives including sleep and mental health with bars of all of that we believe we have developed a highly differentiated medicine of choice for patients with CSU with the unique mechanism of mast cell depletion that directly targets the root cause of CSU. This mechanism is directly tied to the profound clinical benefit patients experience. We look forward to completing the phase three studies while we are actively preparing for a BLA submission in 2027 and potential commercialization. With that, I will ask Diane to talk you through the data. Diane? Thank you, Anthony. I want to echo Anthony's comments. These robust data continue to reinforce that Barzavolumab, with its unique mechanism of action, has the potential to redefine the CSU treatment landscape. It's been seven years since Barzovolumat first entered the clinic, and this rapid development would not have been possible without the support of the CSI community, especially patients, investigators, and study coordinators. Their enthusiasm for and dedication to the Barzavolimab program is the reason why we are so excited to share these data with you today. Turning to slide six, let's review the trial design. The phase three program is designed to establish the efficacy and safety of Barzavalimab in adult patients with CSU who remain symptomatic despite H1 antihistamine treatment. Both Phase III trials are randomized, double-blind, placebo-controlled, parallel-group global studies. 1,939 patients, 963 in Embark CSU1 and 976 in Embork CSU2 were randomized evenly to barzavolumab 150 milligrams every four weeks following a 300 milligram loading dose, barzovolumat 300 milligrams every eight weeks following a 450 milligram loading dose or placebo for 24 weeks at which point patients on placebo were re-randomized to active treatment across both dosing groups 1935 patients were ultimately treated on study and 1634 or 84 percent of patients completed the 24-week placebo-controlled treatment period the total treatment period is 52 weeks. As such, this is an ongoing study and remains blinded until completed. A phase 3B long-term extension study, or LTE, is ongoing, which patients can enter following completion of the phase 3 trial. The primary endpoint of the study evaluates the clinical effect of barzavolumab in reducing urticaria activity, weekly urticari activity score, or UAS-7, at week 12. The study is designed to detect the clinically meaningful difference between each of the active arms versus placebo in the overall population, as well as in the subpopulation of omelizumab refractory patients. The primary endpoint analysis was performed when all patients completed the placebo-controlled portion of the study at 24 weeks. The study was 90% powered to detect at least a 10-point difference between each of the active arms versus placebo in the overall population as well as in the subpopulation of omelette and apophactory patients. The key secondary endpoints are listed on the right-hand side of this slide, and we will review these in more detail shortly. Slide 7 shows the demographic and baseline characteristics of the patients we enrolled into this study. Both studies are very well balanced across all arms and enrolled a diverse patient population with severe disease. As seen in our prior studies, roughly two-thirds of our patient population had severe CSU as demonstrated by a mean UAS-7 score greater than or equal to 28 at baseline. They also had very high rates of angioedema. The Dermatology Life Quality Index indicates a severe population with mean scores of 14 to 16. The DLQI is a validated tool that measures the impact of CSU on daily life, indicating that their CSU had a very large impact on their quality of life. Across the two studies, 288 patients were enrolled who were refractory to omelizumab, representing approximately 16% of patients in CSU1 and 13% of patients in CSU2. Turning to slide 8, we are excited to dive into the efficacy results with you now. On slide 9, let's look at the primary endpoint, mean change from baseline in urticaria activity score over seven days at week 12. UAS-7 is a patient-reported outcome tool. Patients record their daily itch and high severity, which is totaled every week. We observed profound decreases with barzavolumab treatment in UAS7 at week 12. Both barzovolumabs doses are clearly separated from placebo in both trials. The results are clinically meaningful and highly statistically significant. with mean decreases of about 20 points on barzavolamab compared to 10 points in the placebo group, with comparisons having p-values less than 0.00001. As we saw in phase two, the primary endpoint resulted strongly supported by positive data across all key secondary endpoints, shown here on slide 10. For the purposes of today's top-line results, we are going to share the data across the three secondary endpoints we believe are of highest importance to patients and physicians and reflect the greatest unmet needs with current CSU therapies. The proportion of all patients with complete response or UAS7 equal to zero, complete response rates in the subset of patients with disease refractory to omalizumab, and the proportion of patients who had no angioedema symptoms at week 12, as demonstrated by an AAS-7 score of zero in the subset of patients, who had angio-edema at baseline. While we will not review the other key secondary inputs today in detail, all were clinically meaningful and met high statistical significance. Importantly, this efficacy was sustained or deepened from week 12 to 24 across the primary at all key secondary endpoints. We also note that DLQI is not a key secondary endpoint in this trial, but we know that quality of life is important to patients and physicians. We look forward to sharing data on these secondary end points early next year at an upcoming scientific conference that reinforces the profound benefit barzavolumab can have on quality of life. First on slide 11, let's talk about what matters most to patients and physicians, complete response. As a reminder, complete response measured by UAS 7 equals zero indicates the complete absence of itch and hives. Given the importance of this endpoint to patients and physicians and Barzavolimab's unique ability to drive sustained complete response, we are showing you this data at both 12 and 24 weeks. The difference compared to placebo is striking, and by week 12, up to 46% of patients have a complete response, which deepens to up to 54% by week 24. Consistent with phase 2, barzavolumab offers complete response levels that are unprecedented in CSU. Importantly, this profound efficacy is also demonstrated in the patient populations with greatest unmet needs, patients with disease refractory to omalizumab and patients who have angioedema. The proportion of omalazumab refractory patients with complete response at week 12 is shown on slide 12. Our definition of omalyzumab refractory is very strict. who were treated with omalizumab at approved doses for at least three months and whose symptoms never responded, who responded initially but their symptoms subsequently returned, or patients who discontinued omalismab due to intolerance. Again, even with this very high bar, we see results consistent with what is seen in the overall patient population, with clinically meaningful and statistically significant separation from placebo. As is consistent with our mechanism of action, we know that barzavolumab tackles the root cause of CSU and we believe it should have broad applicability across all patient populations. Up to 55% of patients with CSU refractory to omalizumab experience complete response at 12 weeks. These two studies are the first phase three studies to demonstrate efficacy in the omalazumab refractory CSU population, a major advancement in the field. On slide 13, we show the profound benefit for patients with angioedema. Angioedemia is marked by painful, deep, and disfiguring swelling beneath the skin, most commonly on the lips, eyelids, face, hands, feet, or genitals. Angioendema is significantly correlated with higher disease burden, and we believe that barzavolumab has the potential to set a new standard in angioedema control, as shown here. We see clinically meaningful and statistically significant separation from placebo. Up to 74% of patients with angioEDMA baseline achieved complete angioEdMA control at week 12 on barzolomab. As we have now seen across multiple studies in CSU, it is clear that targeting the root cause of the disease yields profound clinical benefits, offering new hope for patients and physicians who need better therapies for this miserable disease. The profound clinical activity demonstrated across the Phase 3 program is supported by a well-tolerated safety profile that is consistent with our Phase 2 barzavolamab experience. Turning to slide 14, let's review safety results from the trials. As shown on slide 15, the combined placebo-controlled safety data set includes almost 2,000 patients observed for 24 weeks. As a standard practice for clinical trials, in phase 2, we reported adverse events observed in 10% of patients or greater. For Phase III studies, you typically report AEs observed in greater than 3% to 5% of patients. For the purposes of this analysis, near reporting at 3% cutoff. Barzavolumab showed favorable safety consistent with prior experience. There were no new meaningful safety signals identified. Across the study on barzobolinav, the vast majority of adverse events observed were mild to moderate, and the most common adverse events are KIT-mediated and expected to be reversible, as we have demonstrated in our Phase II CSU study. The rate of serious events was balanced between placebo and the barzolinav arms. I will provide a brief summary of the serious adverse events reported as treatment-related, which can be attributed to either barzavolumab or placebo. There were two cases of anaphylaxis following the first dose of barzavalumab administration adjudicated by a blinded independent expert committee as probable. The symptoms occurred shortly after dosing, and the patients made a full recovery. A single case of anaphylaxis, adjudicated as probable, occurred following the first dose of placebo in the 300 mg barzopalimab Q8 weak arm. As a reminder of our protocol, to maintain blinding for patients in the 300 mg Q8 week cohort, patients received placebo on alternating visits to match the dosing frequency of the 150 mg Q4 weak arm, This patient tolerated their first Barzal dose well, and then four weeks later, immediately following their first placebo dose, experienced symptoms. The adjudication committee deemed this probable based on the acuteness of the event immediately following blinded placebo treatment. There were five other treatment-related serious adverse events on the two studies. A patient in the placebo arm experienced symptoms after the first placebo dose reported as grade 3 anaphylaxis, which was adjudicated as unlikely. The patient discontinued treatment. In the 150 milligram arm, one patient reported grade 2 urticaria, angioedema, and throat tightness and did not seek medical attention. The patient continued treatment. This potential hypersensitivity event was sent to the adjudication committee and deemed to be consistent with their underlying disease. In the 300-milligram arm, one patient experienced grade 3 anemia and neutropenia that was not associated with infections. Treatment was discontinued, and they fully recovered with barzolamab on board. In the 300-milligram arm, one patient experienced a single grade 2 event of malaise, chest pain, and shortness of breath, recovered, and continues on treatment. A patient experienced symptoms reported as grade 3 anaphylaxis, adjudicated to be unlikely, which occurred following the third dose of placebo in the 300-milligram barzavolamab QAE cohort. To be clear, there were two adjudicated cases of probable anaphylaxis following barzovolamap treatments across both Phase III studies. To date, these two adjuticated cases are the only cases observed across the entire barzavolumab subcutaneous program, including ongoing studies in AD, SD, and CoVu, representing more than 2,400 barzovolumabs treated patients. This is well in line with what you would expect to see with injectable biologics. On slide 16, we are very pleased to see in this robust phase three study that the results indicate that treatment with barzavolamab did not lead to increased rates of infections and there was no association between neutropenia and infection. Most importantly the rates of infection were balanced across placebo and barzavalimab treated patient groups including the rates of serious infections. This supports that barzvalimab did not lead to increase infections. Rates of neutropeny are consistent with Phase II, 9.1% of patients on the 150-milligram arm and 11.7% of patients on 300-milligram arm experienced an adverse event reported as neutropenia. These events were mostly mild to moderate. To summarize, the safety observations from 24 weeks of placebo- controlled treatment in almost 2,000 patients are consistent with the favorable safety profile we observed throughout this program. The safety profile primarily reflects that mechanism-related adverse events are generally mild and without clinical sequelae and are expected to be fully reversible. We believe this safety profile, combined with the unprecedented efficacy, results in a highly favorable benefit-to-risk profile. support our plan to submit a BLA in 2027, and we are making great progress on CMC and other supporting activities required for a successful submission. Turning to slide 17, I will now pass the call over to Terri to talk about the opportunity to bring barzavolumab to patients as we plan for commercialization. Terri? Thank you, Diane. Let's turn to slide 18. With these exceptional results, I want to describe how we see the potential for bars of Olinav to uniquely address large CSU patient populations with significant unmet needs. We have heard time and time again from the CSU community that they are looking for more than just improvement. They aspire to be completely free from their symptoms and the anxiety associated with not knowing when the next flare might occur. In these top-line results, we see barzavolumab's potential to address these needs. Here, we illustrate where we see barsavolamab fitting into the evolving CFU treatment paradigm, addressing two large CFU populations with significant unmet needs. First, we view barzavalumab as a potential first-line advanced therapy of choice for patients presenting with severe disease or with severe angioedema. Earlier, Diane reviewed the exceptional Embark CSU results in delivering both UAS 7 equals 0, meaning complete control of disease at up to 54% of patients at week 24, and AAS 7 equals 0 for complete control of angioedema in up to 74% of patients at week 12. As a reminder, more than two-thirds of patients in our Embark CSU Phase III program were experiencing angioedeema at baseline, with mean AAS scores at baseline over 50, indicating severe angioedaema. Currently, there are no approved CSU therapies with labeling demonstrating angioedinga controls. Drawing your attention to the right of this page, we also believe that Barzogolimab has the potential to be the therapy of choice for second-line advanced CSU treatment in patients who remain symptomatic after treatment with any one of the currently approved therapies. Diane previously shared the profound complete response measured at UAS 7-0 in up to 55% of patients at Week 12 whose disease is refractory to omelizumab. Currently, there are no approved CSU therapies with labeling supporting the use of an advanced therapy refractory CSU. Turning to slide 19, I want to reiterate how thrilled we are with today's results as they establish a strong foundation and prepare us well for potential commercial success. Barzivolumab is a unique, novel, first and only in-class antibody with the potential to deliver efficacy that is highly differentiated on the endpoints most important to CSU patients and their healthcare professionals. Today's positive phase 3 readout amplifies our excitement about the transformational impact Barzivolumab can have for patients and reinforces our confidence in the significant potential of this novel therapy. We remain fully focused on bringing barzavolamab to patients as expeditiously as possible and on executing a streamlined and robust launch strategy that is fitting of this innovative therapy. With that, I will turn it back to Anthony to wrap up. Anthony? Thank you, Terri. Let's turn to slide 20. We are incredibly proud of our progress and execution over the past seven years, delivering on our leadership in mass cell biology and bringing Barzavolumab through to phase three. Today's results mark the next phase of the journey of bringing people with CSU what we believe to be life-changing therapy. These results are unprecedented and offer new hope for patients, physicians, and the CSU community. As demonstrated across the life of barzavolumab program and reinforced in phase three, suppressing KIT with barzavalumab targets the root cause of CSU and leads to rapid, profound, and durable efficacy. The favorable safety profile is also highly consistent with what we've observed in the past experience, which we are incredibly pleased with these large, nearly 2,000 patient trials. We continue to work on bringing this important medicine to patients and are focused on completing the Embark CSU studies and preparing for BLA submission in 2027. As mentioned by Sarah earlier, we plan to submit the 24-week data from the Embarks CSU trials for presentation at Quad AI in February. We also look forward to sharing more about bars of all mass potential and additional indications in the near future. We plan to report to Phase II atopic dermatitis results in the fourth quarter of this year, and our Phase III, SD, and cold-due trials are on track. To conclude, I'd like to thank everyone for your support on our Barzal-Volumab program, especially the patients, and we are excited about the next phase as we prepare to become a commercial stage organization. Thank you for joining us. Before I turn the call back to the operator and opening up the call for questions, I would like to remind you that this is an incredibly large data set, representing nearly 2,000 patients, and we have only recently received it. We are thrilled with the results and want to share them as quickly as possible, and also want to remind that we may not be able to answer questions, every question you may have at this time. Operator, please open the call. Thank you. As a reminder, to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1 again. Our first question comes from the line of Tom Smith with LeRink Partners. Your line is now open. Hi. This is Natura on for Tom Smith. Congrats on the data, and we have a few questions. The first one, on the onset of efficacy, how quickly did you see responses, and How consistent was the experience between OMA-naive and OMA refractory patients? And have a few follow-ups. So we see, you know, we have rapid responses in these studies. We are going to present more about that data at the Quad AI next year. We're very pleased with the rapidity of response that we're seeing. It was still going through the data. We know we see it as early as two weeks. We're looking to see if we see this even earlier, but it's very rapid, as we said. And again, we're going through all the data now, but two weeks at minimum, maybe even faster as we go through the data. Got it. And in the two adjudicated cases of anaphylaxis, can you elaborate more on the clinical course for these patients? Like, was there any additional background that could have contributed to this? And were there any commonalities between these patients that might allow for identification of patients that are at greater risk for anaphylaxis? DR. Yeah. So, you know, as we described, you have two cases of confirmed anaphalaxis, you know, following administration of Barzal across the whole program. know these two cases were adjudicated by an independent anaphylaxis adjudication committee in both of these cases the you know the the onset of symptoms was was rapid in one patient it was 10 minutes and the other was 2.5 hours the you know one one patient was actually had hospitalization the other one was just treated in the clinic and discharged so you know that's less severe so but they You know, they were both found to be probable in the whole axis by degeneration. Got it. Very helpful. Right. And I have you looked at the exposure adjusted rate of anaphylaxis for this sub-Q of basolimab, and how does this compare to other biologics that are approved to treat allergy conditions? We have not looked at the exposure-adjusted rates at this time with this data we're going to get later. But at this point, we have two cases out of 2,400 patients, which compares very favorably with other biologics. Got it. And last question, what are the discontinuation rates observed for these study arms? you give like a brief comment on that? Yeah, so the overall discontinuation rate from the placebo controlled period was 16%. The main reasons for discontinuation were withdrawal of consent by patients as well as adverse events. Thank you. Our next question comes from the line of Yaron Warber with TD Cowan. Your line is now open. Great. Thanks so much. So maybe just a quick question. It looks like the serious adverse events are pretty much identical in the Barzil on to placebo at 1% to 2%. I just want to make sure, is that correct? And can you give us a sense? Yeah, go ahead. No, no. I was just going to say that the rates of serious adverse events are similar between the Barzal-treated groups and the placebo group. And so that's super encouraging. When you're looking at the grade 3 and 4, I mean, you're calling some of them in slide 15. Is there anything else that's worthwhile for us to keep in mind with that respect? Yeah, no. There was also, there was no increase in grade three, grade four adverse events on barzavolumab versus placebo across the study. Okay, amazing. And when you look at skin hypopigmentation, it looks like there were both cases of hyper and hypo. They're all sort of around 10% versus kind of low single. Anything specific worth calling out there? Thanks and congrats on the data. looks really good thank you so so hyperpigmentation you know we've described it before and you really see you know similar picture here hyperpignmentation shows up here we actually have seen that previously we saw that in our phase two studies of CSU and Sindhu the rate was about 4% in those studies, so it didn't make it to our, you know, indicator based on the 10% cutoff. But we do know from the Phase II data that those cases are, you know, mostly mild. They were reversing. And we do believe it's a KIPP-mediated effect because similar events were reported on in that new therapy. And then maybe just a final question. Even in patients who discontinue in the study? Because we know from your previous data that efficacy is fairly durable. Would you still look at their efficacy over time? Thank you. Oh, we will look at the efficacy in the patients who discontinue the study. We haven't gotten to that yet, but we will do that. We expect to see similar numbers. You're on. Thank you. Our next question comes from the line of Yatin Seneha with Guggenheim. Your line is now open. Hey, guys. Thank you for taking my question. Congratulations on very good results. I mean, obviously, the street is a little bit more focused on investors, a little more focused on the safety side today. So quick clarification. So it seems to us that you only have just two cases of anaphylaxis out of these 2,400 patients. So the percentage is much lower than what we see with many biologics. So, the question is, what do you think is the implication for the label, if any? And the reason I ask is that because all these widely used drugs, like even Dupixent, have anaphalaxis and warning flagged on the label. So is that going to be anything different for you? So that's sort of his first question, and then I have a follow-up. Thanks. Yes. So, you know, as we discussed, we have two adjudicated cases following the administration of Barzal across the entirety of our subcutaneous program, which is about 2,400 patients. And these occurred immediately following the first Barzolamab dose. As we said previously, and the data supported, we believe that we will have a label consistent with other biologics. You know, that is something in the warning precaution section, you know, for hypersensitivity and anaphylaxis. Any biologic, with the exception of Zolair and Teva's drug, have similar warning labels for hypers sensitivity and anaphlaxis, and as you know we've been telling that to people for the last four or five years. So these data are extremely encouraging, and two out of 2,400 is well within the range of acceptability. Got it. Very good. Thank you so much. Then just one follow-up on the angioedema benefit that you're seeing. Could you talk about the baseline severity of these patients specifically on angioendema? I mean, I think that's where you also differentiate because I don't know if any other drug has shown that level of benefit on angiodema. So I'd love to understand how that is. Sure. So, just like in the phase two study, the baseline was pretty high. A number of them came in with severe disease, and these data are, you know, replicating the phase two experience, what we're seeing. Very severe patients coming in. The differential between us, our drug, and the placebo patients is obviously statistically significant and much better than what you would experience without the drugs out there. So, on par. This is Terry. I might add two things. One is the placebo delta on these results is the best that's been seen by far with any CSU medicine in any publication. And a reminder of the correlation between the incredibly high burden of disease that comes with angioedema. So these results really speak to the overall impact of these results. Thank you. Our next question comes from the line of Kristin Kluska with Kantor. Your line is now open. Hi everyone. Huge congratulations on these data sets, very impressive. So you mentioned of the 2,400 patients on therapy. Can you just clarify if that includes all studies to date, including other ones that are currently up and running? And just given that it seems that these two cases reported today and the one in PN for anaphylaxis occurred on the very first dose, is there also a case to be made that maybe just if certain physicians are higher risk, they'll just administer the first dose in office? Sure. Sure. So, yes, it is across all current and studies done in subcutaneous. That would include the AD study. That will include the ongoing Phase III, SD, and cold use studies. And we do agree that these two cases, you know, occurred after the first dose as well as the IV case you mentioned. Chris, Kristen, you know, the state HPP and office administration is debating for the launch, and we continue to plan for an auto-injector at the back-home administration, roughly 18 months post-initial approval. Okay, thank you. And then, Teri, you've talked about the two different patient segments where you think you could have the highest unmet need where Barzo could be attractive. the roughly 500k or so, what percent or number of patients do you think are applicable to each of the categories? Thank you so much again. In the first line with severe or angioedema, so we know that 55% of patients overall present with angio edema. There are no published data on the percent of that breakdown, mild, moderate to severe, but the best data that we have access to tells us that up to a third of those with angioligema are categorized as severe angiologema. And then you can see here on the slide, 25% to 30% of patients with CFDs presenting with severe. When we look at the overlap, the intersection of those two, Kristen, we estimate that at about 20% of first-line patients from a large of all and that is uniquely positioned with this clinical profile to be the potential therapy of choice. On the second line data, this is very much evolving. There was no second line advanced CSU therapy until just a few months ago. We do see that number growing, and the trajectory that we see, along with the analogs we've seen in other INI diseases, would project that the second-line advanced therapy market would eclipse the first-line advance therapy market within the first two years of the Bart-Rivola MAP launch. Thank you. Thank you, our next question comes from the line of Sam Flutzke with LifeSite Capital. Your line is now open. Hey, thanks for taking my question. Congrats on a positive update. I guess two for me. One, as you kind of move towards commercialization, could you talk about the build-out as you're thinking about sales reps, ex-U.S., first U.S. plans, and then kind of what has to be done between now and then? And then just a quick clarification, I think I heard you mention 16% dropouts due to AEs. Do you know what the rate was kind of between arms, and then was there anything driving it, or was it pretty dispersed across AEs? Thanks. I'll answer the AE question first. So there was a 16% overall dropout rate in the study. The dropout rates related to AEs was more like 8%. And then the most common ones were, you know, they were low rates, but, you know, were hair color change, you, know, skin pigment changes, and neutropenia. And And it's really very consistent with what we've seen in our previous studies. Sam, let me address your question about the commercial build-out. Obviously, first, these results are unequivocal and give us great confidence in the commercial strategy that we've been discussing for the last several months. In terms of our field team, we will build a competitive, appropriately sized field team. We know, based on the data we're collecting, all of the available public data, tracking it monthly, we know exactly who are the HTTs who are prescribing advanced therapy. And our field footprint plan is to be present with a competitive presence in all of the offices where advanced therapy is being prescribed. You also asked about our U.S. plans. Sam, obviously the U.S. plans, we're going to look and consider several things, including for future indication, future pipeline, and we're looking at the regulatory and policy environment as we go on. So we're look at all of those things to move forward, and once we get a little bit more clarity, we can give you a better update that we're at. Thank you. Our next question comes from the line of Judah Frommer with Morgan Stanley. Your line is now open. Yeah, hi guys, congrats on the data. Thanks for taking the questions. Maybe first, and I apologize if I missed a bit, but what are your thoughts on commercialization of both doses? Could you potentially see pushing the every eight week dose that did not have the anaphylaxis? Could there be kind of different prescribing patterns with one versus the other given the safety profile? Thanks. Thank you for the question. We see the very strong and consistent efficacy and safety across both doses as giving us optionality. We've seen there are certain patients and certain HTPs who like the consistency of the potential for every four-week therapy, which is a very manageable dosing regimen. And we know that there are patients and physicians who would prefer less frequent dosing. That Q8 week dosing, 300 meg Q8 weeks, gives us a very nice potential competitive advantage in terms of frequency. It provides the potential for seven days per year of treatment, which is best in class for any CSU therapy. So we really like the consistency and the optionality, and we'll seek the opportunity to present that optionality in the label. And you're also, remember, you know, we had the cases F-150 and the placebo was F-300. The other two cases that were adjudicated unlikely to be anaphylaxis were both placebo as well. So we don't think it's anything with the 150 or the 300, because as you can see, even patients that got placebo had reactions as well." Got it. Okay. And then just on the hair color changes numerically, those rates look higher than the Phase 2. I don't think there were any placebo hair color changes in the Phase 2. Was there any change in the assay or the investigation on hair color changes between Phase 2 and Phase 3? Yeah, so the hair color changes, as we said, hair color changes are really expected in the study. It's a kid-mediated effect. It's mild. It'S reversible. So we expect hair color changes in the study. A couple of things to note here is that we have longer follow-up in this study. So this is a 24-week placebo-controlled period as opposed to some other earlier studies with shorter follow-ups. But I would say that there's much greater awareness of hair color change. We are looking for them in the studies. We talk about it in the informed consent. The investigators are all aware. So I think people are looking for these things. And we do, in fact, see, as you mentioned, see all these kidney-mediated effects now in placebo. And I think that's the nature of it. It can be kind of a subtle finding and people are more aware, so they're calling it. But it's really just reports of patients and investigators. And Judith, remember also, this is a population that the mean is in the late 40s. So you're expecting to see hair whitening, and that's why you're seeing it also in the placebo. But remember, from the time we started this program in phase one, we were looking for these kit-mediated on-target effects, hypopigmentation, hair color changes, all these things were part of the history of targeting kit. And, you know, as we're learning through clinical development, these are the things that we want to learn. We're not going to shy away from them, But obviously, they have no clinical benefit, I mean, risks. They're completely reversible, as we have seen in our Phase 2, and we'll show it again as the patients go through the Phase 3 program, that these are completely reversible and have no political impact whatsoever. Thanks. Thank you. Our next question comes from the line of Derek Archulow with Wells Fargo. Your line is now open. Hey, good morning, and congrats on the data, and thanks for all the color here. So, just two questions. Is it your intent to file for approval of both doses of Barzo, or is there a case to pursue just one? And then the second question is, just remind us whether you need any longer-term data from this study prior to filing the BLA. Thanks. Margo, can you answer the both doses for Darren? Yeah, we intentionally set out to characterize both doses because we'd like to offer patients optionality. And since the data looks so consistent across them, we will certainly want to support that that's an appropriate way of using the product. On the what else are we going to need, we have been aligned with the agency throughout the development. And so we're certainly going to share this data and then align with them on how to get this drug to patients as quickly as possible. So, we, you know, want to share with them where we are, and then we're going to align with them on where to go. Maybe just to follow up there, I guess the question is really, do you need any, like, longer-term data? Do you need to show, like 52-week data from this study or any additional safety? Well, I mean, this is the 24-week cut with then ongoing data coming in as we're going. So we, you know fully anticipate having these were large studies so we have a lot of data and so we'll be talking you know like we don't know I don't have a crystal ball in terms of what magnitude but we certainly will be sharing with them how this large data set is emerging understood thank you so much again okay sorry no I was going to say we already have over 500 patients treated out to a year or so. Whatever the FDA needs, we're close. Excellent. Thank you. Thank you, our next question comes from the line of Alex Thompson with Stiefel. Your line is now open. Great, thanks for taking our questions. You know, I guess, you know, another one on dosing and thoughts about the label moving forward. How are you, you now, thinking about the addition of the loading dose here relative to phase two? Does it seem to be beneficial relative to, you know, your expectations in terms of clinical efficacy? Is that something that might be up for discussion with FDA, especially when you think about safety profile here? And then when you're thinking about positioning as a second-line option, you now, as with other I&I markets, should we expect premium pricing here relative just from the first-line comps that are out there? Thanks. Yeah, so let's take the first part with Timur, and then Terry can answer the other part. So we believe the loading doses are helpful. We still have data to analyze here, but overall, we certainly don't believe they've contributed at all to a difference in the AE profile. We think our profile in phase three is very consistent with what we had in phase two. Again, our loading doses our modest. just intended to get patients into the level of KIT saturation more rapidly by giving this loading dose. Again, we'll look at the data more carefully, but we think that certainly we know that rapid response is important to patients, and we think these doses have clearly a good safety profile, and I would expect that we will use the loading dose as part of our regimens in the commercial approach. Yeah, and Alex, just to level set everything here. So if you remember in the phase two, the 300 dose was below the 51% that we saw at 150. It was around 37 and a half. And we saw that at the, you know, six to eight week time frame, the300 was coming back a little bit. So in this case, and we saw a, what, a 44% blended rate of response in the stage two study. So when you look at the rates now, the 300 and the 150 are fairly close. So we think that loading dose was helpful here to the point where 44.25 was the blended rate in phase two, and then the phase three rate was 43.6. So the word that keeps coming up with us is consistency on all the data here. And this was the same here. Terry, you want to answer that question on pricing? Sure. Allison, your pricing question. We do believe a substantial differentiation of the overall profile as well as the differentiation in important patient populations that other therapies cannot adequately address. That combination of factors, we do believe, will translate into economic differentiation as well and will support a value-based premium pricing strategy. Thank you. Our next question comes from the line of Richard Law with Goldman Sachs. Your line is now open. Hi, everyone. This is Tawana Usman. I'm for Rich. Thanks for taking our questions, and congrats on the results this morning. To follow up on the earlier label question, I wanted to ask, given the emergence of the two anaphylaxis cases, do you anticipate any risk of a box warning, and if so, how do you anticipate that might impact commercial uptake? No, so as we've said, we really believe that these data are really supporting a label which is consistent with the other biologics out there, which is a warning that includes hypersensitivity including anaphylaxis, and that's what we, it's our expectation. Yeah, I mean, two out of 2,400 patients, do the math, it is extremely low, so we're very happy with it. Thank you. If I could drop in one more on commercial, how do you expect Bargo will be used between chronic and intermittent use in a commercial setting based on efficacy and safety profile you shared today? The CSU is a chronic disease and this is a chronic therapy. That is how we anticipate the label and the intentionality for use. Thank you. Thank you, our next question comes from the line of Andy Chen with Wolff Research, your line is now open. Hi, thank you. This is Jason taking it for Andy. We just want to ask about the neutropenia, so the overall infection rate looks good, but could you break out the infection outcome specifically among patients who develop neutropinia and specifically do those patients have more opportunistic infections or generally more severe infections compared to placebo, and are there any trends of treatment time increasing with infection risk slash rate? Thank you. So, we have absolute, you know, consistency in terms of similarity of rates of infections and serious infections across placebo and barzavolumab-treated groups here, including serious infections. We do not see an association of infections with neutropenia. In terms of the infections, we do not see opportunistic infections. There's really nothing in this data that indicates any sort of infection. Thank you. Appreciate it. Thank you, Susan. Our next question comes from the line of Edso DeRoot with Barclays. Your line is now open. Hey, good morning. This is Gustav for Edso. Congratulations on the data. At launch, what do you think would be the biggest driver of physician adoption versus GED-B or DUPI? Is it more the angiogenetic control, the efficacy of refacturization? I'm sorry, you're coming off very muffled. Can you repeat that? Yes. Can you hear me now? Still a little muffled, but better. Go ahead. Okay. All right. a little bit better go ahead okay all right so uh uh what do you think will be the biggest driver of physician adoption versus remy or dupy is it the angiodermal control the efficacy you're seeing in refractory patients what are your thoughts on that we we see two very large patient cohorts with significant unmet needs where barzavolumab is uniquely positioned to address patient needs, and this is where we see the greatest adoption likelihood. The first is for first-line advanced therapies for patients who have tried highest-dose antihistamines, are still experiencing active disease, and who are presenting with either severe disease or severe angioedema or that combination. For reference, on the size of that opportunity in our Phase II trials, and we're still in part of this, calculating this for our phase three. In our phase two trials, 36% of patients had both severe angioedema and severe CSU. So this is a very meaningful portion of the first line advanced therapy population. The second likely high adoption opportunity for Garzavolumab is as the treatment of choice for second line advanced therapies. So, this is for patients who have tried any one of the currently approved advanced therapies and are still experiencing symptoms. And as we've seen with other INI biologics, INI categories, we would anticipate the second-line advanced therapy market, in fact, to acquit the first-line advance therapy market within the first few years as far as the Volumab launch. As a reminder, there are no other approved CSU therapies. with labeled indications demonstrating efficacy in a biological refractory population. Thank you. This concludes the question and answer session. I'd now like to hand the call back over to Anthony Marucci for closing remarks. Thank you, operator. And I want to thank everybody for joining us this morning. We are extremely happy to be able to present our data set with you at 12 weeks. As we said, we will present the complete data set at Quad AI in February, and we are working hard to go through all the data that we have so far, but we are incredibly happy about our data. We want to thank the physicians, the patients, everyone who has supported us throughout this Phase III program. We got this thing done in less than seven years, which is extraordinary, and we continue to want to show you good data going forward. So we look forward to it, and have a good day. Thank you. This concludes today's conference. Thank you for your participation. You may now disconnect.