Celldex Therapeutics, Inc.

Hello. Welcome to CELF-DEX conference call and 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 the question during the session, you will need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. I would now like to turn the conference over to Sarah Kavanagh. You may begin. Thank you.

Good evening, and thank you all for joining us to discuss the latest results from our Phase 2 Barzavolumab Program in Chronic Spontaneous Cuticaria, or CSU, which are being presented tomorrow morning in a late-breaking oral presentation at the European Academy of Allergy and Clinical Immunology Congress in Glasgow, Scotland. The embargo on the study listed at the start of the call, and this evening we will be discussing the data set in full. Joining me on the call today are Anthony Marucci, Co-Founder, President, and Chief Executive Officer, Dr. Tibor Keller, Co-Founder, Executive Vice President, and Chief Scientific Officer, Dr. Diane Young, Senior Vice President and Chief Medical Officer, and Dr. Margot Hicciozzi, Senior Vice President of Regulatory Affairs. We are also very pleased to be joined by Dr. Martin Metz, Professor, Department of Dermatology and Allergy, Head of Translational Research, and Deputy Head of Clinical Trials at Charité University in Berlin. and the lead investigator for this study. Doctors Yang and Metz are joining us quite late from separate locations in Europe, and I really appreciate that. Please note the slides for tonight's call are available on the Investor Relations section of our website. Tomorrow at 4.12 a.m., when the oral presentation begins, the slides for the presentation will post on our website in the Science section under Publications. Again, the content we are discussing this evening covers the IYAKI presentation in its entirety. Before we begin our discussion, I'd like to direct your attention to slide two with respect to important information regarding the forward-looking statements that today's speakers will be making. Please be advised that a question and answer period will be held later in this call. I'd now like to turn the call over to Anthony.

Thank you, Sarah, and good evening, everyone. Thank you for joining us. In 2020, at the European Academy of Allergy and Clinical Immunology, we presented our first data from the Varzolomab program where we demonstrated that a single dose of Barzol is well tolerated and could profoundly and verbally reduce plasma triptanase, consistent with systemic mast cell suppression. In just five years, we have made remarkable progress. Barzol is now in phase three studies in CSU, enrolling patients around the world, and we are in phase two development in four other indications, chronic inducible urticaria, eosinophilic esophagitis, Virago modularis and atopic dermatitis. This year at IACI, the team will present data from our now completed phase two study in CSU that we believe clearly shows that Barzal is best in disease and can be broadly used for all patients suffering from moderate to severe CSU as shown on slide four. If CSU is a disease of misery and more effective treatment options are needed to help patients regain control of their lives. In this 76-week large randomized phase two study, Barzal consistently demonstrated the highest reported complete response rate in the field at every point in time. Patients experienced rapid complete responses as early as two weeks after the first dose. Response rates continue to deepen over 52 weeks of active treatment, and today we will show you that seven months after completing Barzol treatment, up to 41% of the patients continue to have a complete response. This is important because we know that having a complete response, which means no highs, no itch, is directly correlated with improved patient quality of life. Importantly, we are seeing this benefit across all patients on study, including patients with disease that hasn't responded to omalizumab. We believe this function of addressing the root cause of disease, the mast cell, which is exactly what we set out to do when we began development of Barzal. Barzal's unique profile and data is resonating with the medical community who need new treatment options for this terrible disease. In February of this year, we commissioned an outside research firm to conduct a survey across 205 allergists, dermatologists, nurse practitioners, and physician assistants in the United States who treat patients struggling with CSU. We learned, as you can see on slide five, that these providers largely ranked characteristics tied to efficacy and quality of life as the most important when choosing treatments for CSU. Healthcare provides for them the same survey indicated that approximately two-thirds of their patients with CSU have what they consider to be moderate to severe disease. As we go through the data tonight, I want to keep us in track and bring us back to the patients and the importance of quality of life because it is so often overlooked. As outlined on slide six, 92% of patients report their CSU impacts all aspects of their daily lives, and in a recent publication reported that patients with CSU also suffer from anxiety and depression and are at an increased risk for suicide compared to the general population. Current clinical guidelines recommend that achieving a complete response is the goal of treatment, and patients report that their disease has no impact on their quality of life when they have a complete response. Therefore, this is the goal for patients, for physicians, and for Celldex. To set the stage on slide seven before Diane walks us through the 76-week results, I want to remind you of how this trial data has progressed. First, an incredible 93% of patients on this study experienced a clinically meaningful reduction in disease burden and had either a complete response or milder disease symptoms during the active treatment period. As you can see over the timeline of this Phase II, we initially presented our 12-week data where we met all our primary and secondary endpoints for the study and showed complete response rates up to 51% compared to just 6% placebo. Later in 2024, we presented our 52-week data, and once again, we showed a remarkable complete response rate of up to 71%, which is the highest seen in a well-controlled global study. Tonight, we present our 76-week data set, and we couldn't be more excited about these data and what it means to patients and physicians. We believe we have developed a medicine of choice for all patients with moderate to severe CSU, And we look forward to confirming our data in Phase III studies now being conducted around the world. So, with this as a backdrop, let me ask Diane to walk you through the data in detail. Diane?

Thank you, Anthony. I appreciate all of you joining us tonight. I want to echo Anthony's comments. These data have the potential to redefine the treatment landscape. We have spent the last several weeks discussing these outcomes with members of our clinical advisory board and other experts in the field, and the feedback has been consistent. They have never seen data like this in CSU before. Experts view these data as potentially practice changing, enabling them to have conversations with their patients about what the goal of therapy can look like now, durable, complete response. With confirmatory data from our phase three study, Patients and physicians will be in a position to make a shared treatment decision on whether barzavolumab is the right drug for them based on the patient's individual burden of disease and its impact on their quality of life. On slide nine, we reviewed the trial design. This was a large, randomized, double-blind, placebo-controlled study conducted in patients with antihistamine refractory moderate to severe CSU who were symptomatic despite treatment with up to four times the labeled dose of antihistamines. The study also included patients who had had prior biologics, typically omalizumab. 207 patients were enrolled and treated. The primary endpoint, which we met with high statistical significance, was the mean change from baseline, UAS7, compared with placebo at week 12. The final patient visit for the study was completed in December of 2024. Slide 10 outlines the demographics of the patients we enrolled into this study. The key takeaway here is that the patients on this study had severe CSU. 70% had a UAS7 score greater than 28 at baseline. They had very high rates of angioedema, over 70% on average, which is much higher than the 40 to 50% typically seen in CSU. And roughly 20% had received prior omelizumab. They'd had CSU for a long time and entered the study with mean scores on the Dermatology Life Quality Index, a validated tool that measures the impact of CSU on daily life, ranging from 15.7 to 17.4 out of 30, indicating that CSU had a very large impact on their quality of life. The level of disease severity the patients had prior to treatment really makes these results even more impressive for me. I want to point out that we were also very pleased with the participation in the follow-up portion of the study. 161 patients completed the 52-week treatment period, and 151 of these patients, 94%, also completed the additional six-month follow-up period. This is a very robust data set to work with and gives us great confidence in what we've observed over the longer time period. We have learned a great deal about barzavolumab across this 76-week experience and are really excited about the opportunity ahead of us. Tonight we are going to start with key learnings about safety, beginning on slide 11, And then we will turn to the exciting new efficacy data from the follow-up period. The data continue to reinforce that barzavolumab has a well-tolerated safety profile with a favorable benefit-to-risk ratio. There were no new safety signals identified during the follow-up period, and the most common events across the study are mild, kit-mediated, and importantly, reversible. Let me remind you that Barzobolimab was specifically engineered by Celldex to provide potent but highly specific and durable KIT inhibition through indirect blockade of stem cell factor, the sole KIT ligand. As a result, Barzobolimab drives deep and sustained KIT suppression, resulting in the depletion of mast cells, the root cause of CSU, which is directly tied to the profound clinical benefit patients experienced in the study. As we have discussed in the past, suppressing KIT can result in some side effects that are tied to this mechanism, namely decreases in neutrophil counts and very subtle pigmentation changes of the hair and skin. These changes are almost all mild, don't impact the vast majority of patients, and are fully reversible. We will start first on slide 12 with neutrophil counts. These can be characterized as changes in laboratory values with no clinical significance. There has been no association between neutropenia and infections. The new information here today is that, as expected, during this follow-up period, absolute neutrophil counts returned to where they started at baseline, as seen on the graph on the left of this slide. When patients first take barzavolumab, they experience a decrease in neutrophil counts, typically hitting their lowest count one month from initial dosing. Neutrophil counts stabilize at this lower value with no progressive decline observed with additional doses. Most decreases remain in the normal range. Patients that dip below the normal range are typically patients who come on to study at the lower end of the normal range at study start. As we previously reported, 28 patients had an AE of decreased neutrophil count or neutropenia through the 52-week treatment period, and only 14 of these were confirmed at a second time point. These events were almost all grade 1 or grade 2 with a single confirmed case of grade 3 neutropenia, which dipped to 800 and was increasing on the next sample. Most importantly, these neutrophil decreases resolved quickly while still on barzavolumab treatment. There were no treatment-related effects of neutropenia during the follow-up period. Now let's talk about pigmentation changes. The impact of barzavolumab on skin and hair pigmentation is an expected finding, knowing that KIT contributes to several aspects of melanocyte biology, but not their ability to regenerate. If you look at the pictures on slide 13, you can see these changes are subtle, mild findings. Let's get into the specifics on hair color changes first. Hair color changes are described as small areas or a few strands of hair lightening on the face and or body, as shown in the picture on the left. Through 52 weeks of treatment, these changes were reported in 48 patients, 46 grade one, and two grade two. As expected, greater than 90% of these changes had already fully resolved at study closure, and the remainder, four patients, were expected to fully resolve with a little more time. The median time to onset for these changes was 3.4 months into treatment. Patients who reported hair color changes ranged in age from 18 to 80, with an average age of 42. During the follow-up period, one additional case of hair color change was reported, which also resolved. Turning now to skin pigmentation changes depicted in the photo on the right, these are described as small, very subtle spots of skin lightening on the body or face generally observed on areas of skin that are more exposed to the sun. We reported this for the first time in the 52-week data set as it typically occurred with longer-term treatment in the study. These changes were reported in 30 patients. 28 were Grade 1 and 2 were Grade 2. As expected, greater than 70% of these changes had already fully resolved at study closure, and the remainder, seven patients, were expected to fully resolve with a little more time. The median time to onset for these changes was eight months into treatment. Patients with reported skin hypopigmentation ranged in age from 18 to 62 with an average age of 37. During the follow-up period, six new cases were reported, which is not unexpected given barzavolumab's exposure continues beyond 52 weeks. Only one of these cases was ongoing at last follow-up and is expected to fully resolve. Most patients do not experience these hair and skin pigmentation effects. For those that do, what we consistently hear from investigators is that most patients are not bothered by these changes because they are mild, don't impact their lives, and their urticaria is so much better. This is also reflected in our discontinuation rates. Very few patients discontinued for hair color changes. No one discontinued because of skin hypopigmentation. Importantly, patients with hair and skin color changes report the same high levels of improvement in their quality of life, patients on study who do not experience. This large phase two experience reinforces that Barzavolumab has a well-tolerated safety profile over a long time period with little impact from the mechanism-related adverse effects due to their mild nature, lack of clinical impact, and reversibility. We believe this safety profile results in a favorable benefit-to-risk ratio. Which brings me to the unprecedented efficacy results from the follow-up period of this trial. The line graph on slide 14 showing the improvements in UAS7 scores over 76 weeks really speaks for itself. You can see how rapidly patients improved on drugs, marked by that steep decline in UAS7 scores which continued to improve while on active therapy out to 52 weeks. At week 48, patients had their last dose of barzavolumab, and seven months after completing active therapy at week 76, we see that the improvement in UAS7 is sustained. The mean change in baseline UAS7 score is still greater than 20 points for both the 150 milligram and 300 milligram arms. Slide 15 is my favorite slide. Here we show the complete response rate. As a reminder, complete response means that the UAS7 score was zero. That means no itch and no hives over the past week. Again, we see the same story here. Patients benefited from rapid complete response by two weeks And at 12 weeks, 51% of the patients in the 150 milligram arm had a complete response compared to just 6% on placebo. These complete response rates continue to improve out to week 52, with up to 71% of patients having complete response at that time point. Now, at week 76, seven months after their last dose of barzavolumab, up to 41% of patients still have a complete response a rate of complete response that is higher than many patients experience on active therapy with other treatments. Importantly, these data are in the context of mast cells returning to normal levels. On slide 16 in the bar chart depicted in gray, we show the average baseline tryptase for pooled healthy volunteers across our studies, about four nanograms per milliliter. Next to this, you see the baseline tryptase levels for patients when they entered the phase two study, with patients in the 150 milligram cohort in green and the 300 milligram cohort in blue, both with elevated levels relative to healthy volunteers. Despite profound tryptase suppression through the 52-week active treatment period, at week 76, shown on the right, tryptase levels have returned to the same level as healthy volunteers indicating mast cells have returned, but they have not reached baseline levels. While this study is complete, we suspect with more time, some patients would likely see their tryptase and mast cells rise and symptoms return, but likely some patients would continue to benefit. I'll note that we are encouraged to hear from urticaria experts that they believe the impact and durability of barzavolumab after completion of treatment is both distinctly different and much better than what they would expect to see from spontaneous remission, which can occur in this disease. The consensus from our discussions is that in patient populations comparable to our study, you could expect a 10% to 20% spontaneous remission rate, with most leaning towards the lower end of that range. From my vantage point as a physician, I am very excited that so many patients, 40%, have not had symptoms recur so long after receiving a complete response in the active treatment phase, and that for patients who have had symptoms recur, they have milder symptoms. Let's look at these next. Slide 17 outlines the percentage of patients who had well-controlled disease, which is a UAS 7 less than or equal to 6. Up to 56% of patients had well-controlled disease at week 76. Remembering that most of these patients had severe disease at baseline, a mean UAS7 score of 30. This is a remarkable level of improvement that has been sustained seven months after their last dose. Slides 18 and 19 speak to why these data matter to patients and physicians. Slide 18 shows you the time course of improvement in patient quality of life. Let me orient you to this slide. The y-axis shows the scale of DLQI scores. A high score means that a patient's quality of life is more negatively impacted by their disease, and decreasing scores mean their quality of life is improving. Here you can see patients start the study with high baseline scores, which plummet rapidly after treatment with Barzal and then continue to improve over the course of active treatment. And if you look to the right of the chart, seven months after completing dosing, up to 48% of patients continue to report that CSU has no impact on their daily quality of life. This is the goal of treatment for patients, to be able to live a life not controlled by their disease. Moving to slide 19, as Anthony said at the start of the call, Complete response is the goal of treatment, and literature on this topic states that achieving complete response is directly correlated to the greatest improvements in quality of life for patients. Barzavalimab has consistently shown the highest rates of complete response at all analysis time points. The impact of achieving this level of complete response is clearly reflected in patients' improved quality of life. We see these results across all patients on the study, including in patients with CSU refractory to omelizumab. These results are unprecedented and offer new hope for patients and physicians who need better therapy for this miserable disease. It is clear that deep and durable kit suppression by our unique approach with barzivalumab targeting the root cause of the disease yields profound clinical benefit that leads to improved quality of life. We believe barzavolumab's overall safety and efficacy profile clearly supports that barzavolumab can become the drug of choice for patients with antihistamine refractory moderate to severe CSU and gives us great confidence in the ongoing phase three studies, which are enrolling the same patient population. Before I hand the call over to Anthony, I want to thank the patients and physicians who participated in this study. A 76-week study is a large commitment, and we truly appreciate the role they all played in the successful execution of this study. Anthony?

Thank you, Diane. We are proud of our progress in execution over the past five years and believe it has become clear that Barzell offers new hope for patients suffering from CSU. We have demonstrated unparalleled complete response rates, which achieve the ultimate goal of therapy for patients, a complete resolution of their symptoms. This efficacy, combined with the rapid and prolonged responses shown with the data presented tonight, drives meaningful transformative improvements in patient quality of life. Targeting the root cause of disease also enables Barzal to offer patients with disease refractory to omalizumab a potential new treatment options, which they currently do not have. We believe the clear, positive benefit-to-risk ratio is being recognized by patients and physicians and supports that Barzol can become the drug of choice for patients with moderate to severe CSU. We continue to work to bring this important medicine to patients and are executing across our Phase III program, comprised of two clinical studies, each recruiting approximately 915 patients across 40 countries. We initiated the phase three program last summer and are on track to complete enrollment in the summer of 2026, as we initially guided. We have seen a high degree of excitement around Barzal in the physician community, which has certainly played an important role in recruitment across all our Barzal studies. And our team is looking forward to talking about these latest results with the community at Iachee. Tonight, we are also joined by Dr. Metz, who played a leadership role along with the late Dr. Marcus Maurer at Jarte in the Barzell Development Program since its earliest days. Dr. Metz has participated across a number of our Barzell studies and is the head investigator for this Phase II study. His exceptional background in mast cell biology and mast cell-mediated diseases, including CSU, has been invaluable to us and to the greater field. I would like to ask him to provide his thoughts on the data we share tonight, and we look forward to taking your questions. Dr. Metz.

Yes, thank you, Anthony. So actually, I don't think that I have much to say because the data really does speak for itself. So let me start with what you said, Anthony, at the beginning. And this is something that we always have to remember. CSU is a disease of misery. These patients suffer. They suffer very, very badly. And therefore, the guidelines have been recommending for quite some time now that the goal of treatment is the absence of symptoms. So really, no hives, no itch. And up to now, none of the treatments have been able to achieve this in a large number of patients. And this is what we see now, and this is what we want to see. So our patients have something to look out for in the future with a drug that works so fantastic. And let me highlight two aspects of the efficacy that I find most compelling. And the one is, as I just said, the high rate of complete control. But the other, and I have to admit that this is more surprising to me, is the sustained control even after cessation of treatment, after stopping of treatment. So seven months after the last dose, there's still such a high rate of responders. That's fascinating and interesting, and we have to look into that in more detail, but it clearly shows that there is some sort of normalization happening in these patients, and this is really great to see. Finally, one word on safety, but Diane mentioned it all and gave the details and background on it. But I just want to support what she said because we have many patients in these trials and we had patients that experienced white hair and some of these kid-mediated adverse events and Actually, none of them cared because their disease was gone. And this is what we have to be aware of. It's what the patients feel, what the patients experience. And this is the absence of signs and symptoms. And this is what they want to achieve. And therefore, it should also be what we as physicians want to achieve. So in summary, I'm really very, very happy about the data that will be presented tomorrow at the key. Thank you.

Thank you, Dr. Metz.

Great. So operator, at this point, we're ready for the Q&A. I will let folks know it's very late over in Europe. We'll take as many calls as we questions as we can. We're not going to be able to get through them all just by looking at the queue. And for anyone that we can't get to tonight, feel free to text me or call me and we'll make sure that we get your questions answered as quickly as possible. So operator, at this point, we're ready for Q&A.

Thank you. As a reminder, ladies and gentlemen, to ask the question, please press star 11 on your telephone, then wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Thomas Smith with LeeRink Partners. Your line is open.

Hey, guys. Congrats on the stellar data, and thanks for taking our questions. Just on efficacy, in the analyses that you've completed to date, have you been able to tease out any common characteristics in the patients that are still experiencing complete response at that 76-week time point? Is there any relationship with baseline disease severity or prior biologic experience? And then I was hoping you could provide some updated thoughts on how you think these data might change the value proposition for Barzo. It seems like you're having a pretty dramatic, profound, remittive effect in some patients. And just wondering if you could provide some updated thoughts on how you're thinking about things like treatment duration on average per patient and perhaps even pricing. Thanks so much.

Sure, Tom. I'll let Tibor handle the first question. I'll be happy to answer the second question.

Hi, this is Keyboard. So obviously, we're extremely interested in understanding any correlations with the patients that are experiencing this really profound, complete response and durable, complete response. We're still in the midst of doing that analysis, Tom. What I can tell you now is that the patients that have these responses are across all different endotypes and characteristics, there's nothing jumping out at us. And this is consistent with our perspective that we believe all patients are able to benefit from Barzo. So, we will continue to investigate any specifics, but as we see it so far, there's really not any obvious characteristics that define those patient populations.

Yeah, and Tom, as far as the 2nd question, we are obviously thrilled with these data that we're seeing here and we were able to follow them out for 28 weeks or 7 months. So the most we can say here is that we, after a year's worth of therapy, we're seeing some really good continued response rates. But we also believe that. they're going to be patients that their disease will come back. And when they do, we think that Barzal will be an extremely appropriate therapy for them, because we also believe they will respond to that. So, we just think that we've improved the optionality for docs and physicians going forward. And so, I just think this is a positive overall.

Got it. That makes sense. And if I could just sneak in one follow-up here on Stacey. I appreciate all the details around the hair color change and the hypopigmentation, particularly around the onset of these effects. I was wondering if you have any more granularity around the average time to resolution. I know we have the resolution rates at seven months after treatment discontinuation, but can you comment on sort of the average time to resolution with any more precision?

Sure. Diane, do you want to take that one?

As we said, the hair color changes start earlier, so the median time to onset was about 3.4 months. The median time to resolution of hair color changes were 5.6 months. For the hypopigmentation, that occurred later, as we said, the median time to onset was 8 months, and the median time to resolution was 7.3 months.

Got it. That's super helpful. Thanks for taking the questions, guys, and congrats again on the data.

Thanks, Tom.

Please stand by for our next question. Our next question comes from the line of Yaron Webber with TD Cohen. Your line is open.

Hi, this is Gina on for Yaron. Congrats on some really amazing data, and thanks for taking our questions. Brother, I want to ask how do you think this data is going to impact physician choices particularly for dermatologists when between barzavolumab and naldepixen and potentially remibrutinib in terms of how they sequence treatment options. And then on safety, I wanted to ask if there was anything that you wanted to point out on taste changes when those occurred and how fast those resolved and also how burdensome that typically is for patients. Thanks so much.

Yeah, so, you know, how they sequence is remains to be seen. You know, what we can talk about is how we think our data stacks up and as far as what we saw in our phase two study. So, you know, as Diane said on the call, we did accrue a more severe patient population in the study. We allowed up to 4X antihistamines as part of the background. whereas OMA and REMI only allowed up to 1X. We had the greatest number of patients with angioedema at baseline. As Diane said, we had the highest mean DLQI scores coming in. We also had a larger portion of the population, 20%, which were either OMA experienced or refractory. So I think all of these things go into giving the dots a great option to treat the patients, whether they're moderate to severe or have these other issues in combination. So we don't look at it as where it fits in. We always look at how many patients we believe we can treat with Barzal. And I think that these face-to-face data show us that we can treat them all, as we've always said. That's what we're most proud of here.

And I think for the taste changes, Diane, can you address that?

Yeah, sure. So, you know, taste changes are believed to be a kit-mediated effect. In this study, taste changes were not one of the most common AEs. It was less than 4%, I believe. They were mild. They're kind of subtle, like people have trouble you know, tasting salt or umami flavors. And very interestingly, the taste changes tend to occur fairly early and also reverse while patients are still on therapy. So it's kind of interesting, but it's really not that common in the study.

Thanks so much. Thank you. Please stand by for our next question. Our next question comes from the line of Christine Kluska with Canada Fitzgerald. Your line is open.

Hi, congratulations on pioneering this study and the data that you showed. So I wanted to ask mechanistically from a deeper level, what do you think these data tell you about the potential of the impact on resetting the immune system or essentially what's underlying going on, especially if the trip case levels are coming back, yet you're still seeing such a high response rate.

Hi, Kristen. So, yeah, this is something we obviously are spending a lot of time thinking about. We're so impressed with these data, and as you may know, we don't have real insights as we're not taking biopsies in this study. What I really think the prime reason for these great results is the unique mechanism of being able to deplete MAD cells, but also be engineered in long half-life for the antibody. RPK results suggest the antibody will clear in about three to four months in most patients, so that certainly doesn't account for all of it. We see that tryptanes and MAD cells are coming back, which we still are in the absence of symptoms. I do expect, as Diane mentioned, that likely with longer follow-up, some of these patients are going to have some of their symptoms returned, so we don't know whether they're in true remission or not. But we don't take further analyses and perhaps biopsy studies or more in-depth analyses in other studies to better understand mechanistically what's truly changed in these patients to support their incredibly durable, complete responses.

Thanks, all. Thank you. Please stand by for our next question. Our next question comes from the line of Yatin with Guggenheim. Your line is open.

Hey, guys. Thank you for taking my question. Let me add my congratulations as well on these remarkable data. So two for me, could you just talk about, I think you touched on it a little bit, but I'd love to hear about, you know, the durability of the fact that you might be seeing in these OMAR-exposed patients, how consistent was the response in patients that have Zolaire in the past. And then, you know, just from a Adoption perspective, could you just talk about the concept of introducing drug holiday in patient who has achieved a CR after a particular duration? How could that work? Because again, the durability seems pretty remarkable here. Thank you.

Diane, do you want to take that? And perhaps even Dr. Metz, if he wants to add on to the conversation, that'd be great.

Sure. Well, I'll start. This is Diane. So when we look at the omalizumab-experienced patients and we superimpose that curve on the figures that you've seen, it has the same pattern. So consistent with other studies that we've done, you know, Barzal appears to work in patients just as well, whether they're, you know, oma-naive or oma-refractory. Yeah.

I can just add to that. There's no reason to believe that there is any differential response because we know that the response to omalizumab is depending on the underlying type of autoimmunity in these patients, so how the muscles are activated. And that doesn't matter for basal volumab because they you get rid of the mast cells. So we don't have to care about how the mast cell gets activated. So I'm not at all surprised to see no difference whatsoever in the response of patients that were previously not responsive to Omanizumab as compared to those where Oman is.

Thank you.

And Diane? Dianne, I think Dianne also wants to know about introducing a drug holiday, as he's put it.

Yes. So what these data show is that, you know, you get the best results with 52 weeks of treatment, and that that gives you, you know, a 70% complete response rate and does give you these sustained responses if you stop treatment. We think that with these data, if they're confirmed in phase three, that physicians are really going to talk to their patients and use shared decision-making and decide how to use this drug, just as they do for the other biologics that are out there.

Thank you.

Please stand by for our next question. Our next question comes from the line of Sam Fluske with Lifestyle Capital. Your line is open.

Hey, good evening, everyone. Great work on the update. Two for me, I guess. For the cases of skin hypopigmentation that are still ongoing as far as the hair color changes, is there any change to indicate that they are getting better and maybe just haven't fully resolved yet? Or what's that kind of kinetics look like for the ongoing ones? Sure. Diane?

Yeah, so, you know, as we said, there are very few cases that are still ongoing. You know, it's not really surprising, you know, for skin hypopigmentation in particular, which occurred later to take, you know, longer to be resolving. But in fact, all the ones that remain are grade one, and we do have anecdotal notes from the physicians saying that they are improving. So, you know, we... really expect these to completely resolve. I mean, it's very, you know, the mechanism of all this is very well known with other kit inhibitors. And, you know, that's what we're seeing. They just need a little more time to completely resolve.

Okay. And then on second question, just any details on kind of what the dropout rate looked like between weeks 52 and 76? And should we be thinking about the denominator similarly of patients?

Diane?

Yes, so this is Diane. So, yeah, so we're really pleased with the great retention rate we had in that portion of the study. So there were, you know, 161 patients who completed the 52 weeks of treatment, and 151 of them completed the follow-up, which is 94% rate. And that's really pretty amazing considering, you know, they were off treatment and this was going out to 76 weeks. Of the 10 patients who discontinued, most of them were due to not being able to come to clinic or not wanting to participate with the diaries and things like that. There were just three that were due to lack of efficacy in the 10 that discontinued, and that would not significantly affect our results.

Excellent. Okay. Thank you.

Thank you. Thank you. Please stand by for our next question. Our next question comes from the line of Judah Frummer with Morgan Stanley. Your line is open.

Hi, and I'll add my congratulations on the update. More of a high level question in terms of positioning the drug within the patient population. I guess what sticks out from the data today that would maybe allow you to better market or target the drug for more moderate patients within the moderate to severe spectrum. Thanks.

Diane, would you like to take that and I can also follow up?

Yes. So, I think what these data support, and hopefully will be confirmed in phase three, that barzavolumab really works in all patients who have antihistamine refractory CSU. The overall population was moderate to severe. It works as well in moderate as severe patients. It works in patients that have had prior omelizumab. And it has a very favorable benefit to risk profile. So we believe that it could be used in all patients.

Yeah, Juno, I think, again, the fact that we know and believe now, again, that we can treat all patients, whether you're moderate or to severe, I just think it just gives patients and docs that other option now that they can talk about. And the fact that they can get to resolution of their disease fairly quickly and maintain it, I think that just gives them a great option that they didn't have before.

Thanks. And if I could just squeeze one more in. In the doc survey that you mentioned, was there anything about, you know, how docs are feeling about monitoring patients, I guess, specifically for the neutropenia, but anything on that side of the profile?

Nothing that stood out remarkably. I mean, obviously, the derms were a little bit more sensitive to doing any kind of monitoring than the allergists would be. I guess the top things were quality of life and getting a patient to a good response, good safety profile. Monitoring didn't even enter the top seven or eight categories, but it was mentioned briefly, and if anything, it was more on the derm side, but nothing of significance.

Thanks.

Please stand by for our next question. Our next question comes from the line of David Leibowitz with Citi. Your line is open.

Hi there, guys. Thanks for taking the question. This question is for mostly the doctors on the call. When we look at the slight degradation in efficacy between the 150 mcq four weeks and the 300 mcq eight weeks, what's your understanding about what kind of trade-off patients and physicians, prescribers would tolerate, I guess. And I'm sorry if this question sounds like the data is not amazing. It clearly is. Just trying to get a sense for, you know, what the trade-off is and what sentiment and what you're thinking in that respect.

Thank you. Okay. Diane, why don't you start, and we can have two more follow-up questions.

Yeah, so I think that, first of all, both 150 milligrams Q4 and 300 milligrams Q8 had positive outcomes on the study, and the study wasn't designed to look at a difference between the two. I will say that there are some differences in the population that the The 300 tend to be heavier and they tend to have more severe disease if you look at the demographics. And there's also a suggestion when you look at the curves that the initial dose for the 300 Q8 weeks may not be enough to keep tryptase down and symptoms down out to eight weeks. So we have, when we've gone to phase three, we've added a loading dose to try to get, you know, a more rapid onset of, you know, of response and maintenance of response in the beginning with the 300 milligram dose. And we think it could benefit the 150 as well.

Yeah, just to follow up on that, that we did recognize in this study that the 300 milligram Dosing in the beginning of this study resulted in waning of the effects after the 1st, initial doses. And that's something that we believe we will be showing to eliminate in the phase 3 with those loading doses. So fully expect the 300 milligrams. to look much more like the 150 milligrams when we have our phase three results and expect to be able to give patients the option of the monthly or the every other month dosing.

Got it. Thanks for the thoughts. Congrats on the progress. Thank you.

Thank you. Ladies and gentlemen, at this time, I would now like to turn the call back over to Mr. Marucci for closing remarks.

Thank you, operator. We know it's getting late here in the States and even later to Diane and Dr. Metz and Scott. And we all appreciate you joining us on the call tonight to discuss these exciting data. And we wish you all a good night. Thank you.

Ladies and gentlemen, that concludes today's conference call. Thank you for your participation. You may now disconnect.