Thank you for standing by. Welcome to the Jasper Therapeutics Data Update Webinar. At this time, all attendees are in a listen-only mode. A question-and-answer session will follow the formal presentations. To our covering analysts joining us live, please raise your hand to indicate you have a question and join the queue. As a reminder, this call is being recorded, and a replay will be made available on the Jasper Investor Relations website following the conclusion of the event. I'd now like to hand the call over to Jasper's Head of Investor Relations, Alex Gray. Please go ahead, Alex. Thank you, Wilson, and thank you for those listening in today. Joining us for the prepared remarks are Ronald Martell, CEO; Dr. Daniel Adelman, Acting CMO; and Dr. Martin Metz, Professor of Dermatology and Allergy at Charité in Berlin. Also on the line is Herb Cross, CFO, who will be available during the Q&A session. We will be presenting slides on today's call, which are available via the webinar link and posted to our Investor Relations website. During today's event, we will be making forward-looking statements based on our estimates and assumptions and our current expectations and projections about future events. All statements other than statements of historical fact made during today's event are forward-looking statements. These statements are subject to a number of risks, assumptions, and uncertainties, any of which may be significant, and our actual results may differ materially and adversely from those stated or implied in any forward-looking statements. For a description of risks and factors that could affect our future financial results and business, please refer to the disclosure and the accompanying slides. Our most recent Forms 10-K and 10-Q, and the reports that we have filed or may file in Form 8-K with the Securities and Exchange Commission. All our statements are made as of today, December 2, 2025, based on information currently available to us. We can give no assurance that these statements will prove to be correct, and you should not rely on any forward-looking statements as predictions of future events. We undertake no duty to update any forward-looking statements except as required by law. I'll now hand the call over to Ronald Martell. Ron? Good morning, and thank you for joining us this morning. On today's call, we will begin by reviewing findings from our internal investigation into the unexpected efficacy results observed in the BEACON trial in CSU, or chronic spontaneous urticaria, first reported in July. We will then turn it over to Dr. Metz to present the redosing data from the affected cohorts in BEACON and provide his comments on the investigation. Finally, we will discuss the initial results from the ETESIAN study evaluating briquilimab in allergic asthma. As a reminder, in July, we presented data from cohorts 8 and 9 of the BEACON study showing an unexpected lack of clinical response. None of the 10 patients enrolled in the U.S. achieved complete response or well-controlled UAS7 by week 12, which was a sharp departure from what we've seen previously. All 10 patients were dosed Lot A34954, which was the first time it was introduced into the BEACON study. Two of the three patients in the EU sites achieved CRs. However, the EU sites used a different lot of drug. We immediately replaced drug Lot 34954 with Lot 34955, which was being used at sites in the EU as well as in the open-label extension study. We also launched an internal investigation into the results, including a comprehensive review of all manufacturing records, drug handling, site training and site logs, and data handling. Additionally, samples of drug substance and drug product from across the supply chain were recovered and tested internally and by an independent lab. We also reviewed all the U.S. sites and the U.S. patients, which included protocol adherence, patient medical history, patient screening, and all PK, PD, and efficacy data. Finally, we convened a panel of independent experts in CMC and in clinical urticaria to review the findings of the internal investigation, which included manufacturing and analytical records as well as full patient dossiers. I'll now hand it over to Dr. Adelman to review the findings from the investigation. Dan? Thank you, Ron, and good morning. Before reviewing the results of the investigation and the redosing data, I'd like to provide a quick reminder on the trial design. The cohorts that we will be Cohort 8, in which the patients were administered 240 mg of briquilimab Cohort 9, where a loading dose of 240 mg was given, followed by 180 mg every eight weeks. We enrolled a total of 17 patients across two cohorts. Thirteen received active drug, and four received placebo. Of the 13 patients receiving active drug, three were enrolled at sites in the European Union. The other 10 were enrolled at sites in the United States and are the subject of our investigation. Moving to PK and PD results, as you can see, the pharmacokinetics in cohorts 6, 8, and 9 are all quite consistent. Similarly, the effect on tryptase levels observed in cohorts 8 and 9 are consistent Cohort 6, which evaluated a single dose of 240 mg. Cohort 6 did achieve slightly higher Cmax's and slightly deeper tryptase reduction on average, the results are within the normal variation that we would expect for cohorts of this size. These results demonstrate consistent PK and PD across the different lots of drug used in the study. Furthermore, there is no indication from these data of any variation in results due to the drug product Cohort 8 and 9. going one step further, this slide shows PK and PD effects on tryptase levels from cohorts 6 through 9, broken out by response, with patients receiving CR or well-controlled disease shown in blue and non-responding patients shown in red. Once again, the pharmacokinetics and pharmacodynamic effects on tryptase levels observed are consistent across the two groups, while the UAS7 in the right panel shows the dramatic difference in clinical outcomes. Together, these data tell us that the drug was present at therapeutic levels and that the mast cell depletion was occurring, even in patients who did not respond to treatment, suggesting that the investigational drug was not the problem, but rather patient-specific factors were most likely the cause of the unexpected results. This slide includes a selection of the analyses conducted by Jasper and by independent labs to confirm potency of the drug product samples from across the Lot A34954 compared to reference standards. As you can see, physical, chemical, and in vitro cell line experiments show no difference in briquilimab lots or clinical samples. Additionally, there are no significant deviations or issues with drug product or drug substance uncovered in our investigation. Concurrently, we assessed clinical operations, data management, and our clinical sites. We conducted a thorough examination which did not reveal meaningful deviations in drug substance and drug product manufacturing, drug kitting, shipment and storage, injection preparation, timing and storage, types of syringes, injection volume or site, or patient and site data entry, data management, and analysis. We also reviewed site-specific screening and dosing data for each patient and prepared comprehensive patient folios for review by a CSU KOL panel. We did have one new clinical site that enrolled five patients in active arms of cohorts 8 and 9, with none achieving CRs or well-controlled disease. These were the first BEACON patients enrolled at this site, which is a community-based clinical research center. Taken together, the PK and PD data, our investigation indicates that patient-specific factors were the most likely cause of the unexpected results and that many, if not most, of the patients enrolled at the new clinical site likely did not have CSU. I'll now turn it over to Dr. Metz to present the updated results from cohorts 8 and 9 following redosing, as well as provide his opinion on the investigation. Martin? Thank you very much, Dan. Yeah, so I'm a clinician investigator, and I am participating in the BEACON study and help Jasper in understanding this, well, unexpected and unlikely efficacy results that you have just seen. This is basically summarizing the data that I will present in the next slides on the cohorts 8 and 9. You see that as part of the internal investigation, the patients Cohort 8 and 9 were switched to the new lot during the 24-week dosing period. This 5/4 lot was then replaced at all clinical sites with the 5/5 lot that was used and is used in the open-label extension here in Europe in the BEACON trial. What you will see is that after transitioning of the U.S. patients to a different lot, no changes were seen in the PK and PD measures, and also no changes in the efficacy outcome when they were redosed. There was one patient who did achieve well-controlled disease after third dose, but this patient already had a quite substantial drop in the UAS7 already after the first two doses with the initial lot. Going to the next slide. This is basically showing it all, I think, because it does show that the lot in question was doing what it was supposed to be doing, and that is depleting mast cell. We are looking at the total serum tryptase measured in these patients, and you see a robust reduction in the tryptase that is sustained also after the change of the lot. For both lots, you have the effective and expected reduction in the tryptase levels. When we look at the urticaria activity score, you see in the orange line, the 240 mg single dose stays the same after the lot was changed to the 34955 lot. This was consistent also in the efficacy with this, unexpected reduced efficacy that, for me, would be supportive that the patients we're looking at here do not have a mast cell-mediated disease and therefore not a chronic spontaneous urticaria. I mentioned before that there was this one patient who showed a well-controlled disease within the first treatment period, with the 34954 lot, but you can also appreciate that there was a substantial drop in the UAS7 at the beginning, and this further improved over time. This is a late responder, something that we do see in clinical trials, including targeted clinical trials. Taken together, this clearly states that, as I said before, the drug was doing what it was supposed to be doing. The c-Kit-mediated depletion of mast cell by looking at the reduced tryptase levels clearly shows that it works, and therefore we can look at the safety. We can completely take the results that we see in the safety to completely evaluate the drug in our patients. When you look at the overall safety, this is still, as before, a very encouraging safety tolerability result with very low rates of adverse events and treatment- emerging adverse events. This is unchanged, by the way, for the two different lots. This is also true for the c-Kit-related safety data, where we do see low rates of hair color changes. We do not see any skin discoloration. We do see taste change and neutrophil count decrease. In the rates that we have seen before, this further shows that the drug at question was and is doing what it was supposed to be doing. To conclude these investigations, I'm really confident to say that the, I call it weird or anOmalous efficacy, does not appear to be the result of an issue with the study drug or with the study conduct. There were no issues with deviations, as mentioned by Dan, and the Cohort 8 and 9 patients did not drive a different outcome in efficacy nor in safety. As mentioned before, there were no protocol deviations, issues with site training, and so on and so forth. We and I personally also do think and am convinced that this unexpected efficacy result is largely to be the result of patient selection, of bad patient selection. The KOL panel reviewed all of the data, especially the tryptase and efficacy data and the safety data, and the conclusion that we as the panel had was that 9 out of the 10 patients that did not show any response appeared to not have chronic spontaneous urticaria, so no mast cell-driven disease. This does happen, and it for sure has happened in basically every larger clinical trial before. Chronic spontaneous urticaria is a disease that is diagnosed based on the clinical experience. There is the possibility that there are patients in there that do not have CSU, but, for example, urticaria vasculitis that is not mast cell-mediated. It is likely that these patients also have been included in other studies, where they have also been non-responders, even though we cannot give concrete numbers on this. The solution from this, or the recommendation, important recommendation for the future, both for Jasper but also for other companies investigating chronic spontaneous urticaria, is to really ensure quality patient selection. This is crucial. Our recommendation is to have a certified immunologist or dermatologist who knows CSU. That means he or she should have a history of diagnosing, but also treating chronic spontaneous urticaria patients. Maybe also an expanded review of patient history during screening can help making the right diagnosis, including visual records of lesions on smartphones. In the end, of course, as always, larger sample size will certainly mitigate an impact of non-mast cell-driven chronic spontaneous urticaria patients. Thank you. Thank you, Dr. Metz, and thank you for participating on the call today, as well as your work as an investigator in the BEACON trial and as a member of the KOL panel. Dr. Metz will be available during the Q&A session at the end of the call. I'd now like to hand the call back over to Dan to review our exciting new data from the ETESIAN study. Dan. Thanks, Ron. Before we review the data, I'll quickly review the ETESIAN trial design and objectives. The primary objective was to assess the safety and efficacy of briquilimab in patients with mild allergic asthma in response to an allergen challenge. The primary efficacy response was measured as the late asthmatic response. Additionally, we assessed changes in the early asthmatic response, as well as the airway hyperresponsiveness to a methacholine challenge and the effects of the drug on serum tryptase levels and sputum eosinophils. The ETESIAN trial was a double-blind placebo-controlled challenge study evaluating a single 180 mg dose of briquilimab in patients with a diagnosis of mild allergic asthma. Patients were given a baseline allergen challenge prior to dosing, followed by additional challenges at week 6 and week 12 following dosing. On today's call, we'll review data from the 14 patients who completed at least the week 6 allergen challenge assessment. Eight were on active drug, six on placebo. This slide shows the effects of briquilimab on serum tryptase levels. A single 180 mg dose of briquilimab resulted in serum tryptase reductions at six weeks, which is similar to the tryptase reductions observed at 180 mg with briquilimab in BEACON, SPOTLIGHT in our chronic urticaria open-label extension study. Looking at the FEV1 response following allergen challenge at baseline and six weeks post-dosing, 12 weeks post-dosing for the placebo and the active dose groups, we see clear separation of the response curves at both 6 and 12 weeks for patients receiving briquilimab and little effect for patients receiving placebo, indicating a remarkable and sustained effect of mast cell depletion on the early and especially the late asthmatic response. On the next slide, we see that we have two example patients showing the effect of briquilimab, showing the effect that briquilimab can have on early and late asthmatic responses. These patients were two of the responders in this initial study, and the other briquilimab patients also had improvements in early and late asthmatic responses. For patients receiving briquilimab, more methacholine was required to evoke a 20% drop in FEV1 in the post to pre-challenge comparison at weeks 6 and 12 compared to baseline. These data demonstrate the potential of briquilimab to dramatically reduce airway hyperresponsiveness following allergen challenge. Here we show sputum eosinophil responses to allergen challenges conducted at screening, six weeks, and 12 weeks. Patients receiving briquilimab had less accumulation of sputum eosinophils and a diminished response to allergen challenge when compared to either pre-dose challenge or placebo. Sputum eosinophils are known to be a key driver of asthmatic symptoms, and as you can see, treatment with briquilimab clearly suppresses sputum eosinophil response following allergen challenge at 6 and 12 weeks post-dosing. Moving to safety, we're pleased to see that briquilimab was well tolerated in this asthmatic population, with no grade 3 or serious treatment-related adverse events observed. We are further encouraged to see that safety observations possibly related to c-Kit blockade were limited to low-grade events. While ETESIAN was a small study, the initial results provide proof of concept for the use of briquilimab in asthma. The PD data demonstrated deep and sustained biologic effects on key biomarkers driven by briquilimab, including serum tryptase and the accumulation of sputum eosinophils. There were substantial improvements in the early and late asthmatic responses observed in the allergen challenge and reductions in airway hyperresponsiveness. This study shows for the first time that a potent c-Kit-specific therapeutic that targets the mast cell has therapeutic potential for the treatment of asthma. Given that the mast cell may be the central actor in both T2 high and T2 low disease, further investigation of the effects of briquilimab in all asthma endotypes is warranted. We are currently evaluating next steps for development, including potential dose-ranging repeat dose studies in a broader asthmatic population. I'll now hand it back over to Ron to summarize today's updates and review our upcoming milestones. Ron? Thank you, Dan. To wrap up today's remarks, I'd like to review the status of our programs following today's update and look ahead to our upcoming milestones. In CSU, briquilimab has demonstrated the ability to drive rapid onset of deep clinical responses with an encouraging safety profile seen with repeat doses in cohorts 8 and 9. We plan to report additional BEACON data and open-label extension data in the first quarter of next year, which will enable us to finalize our phase IIb dose selection. In addition, in the update, we'll include the efficacy and safety data on additional patients enrolled in the BEACON study, as well as 24+ weeks of safety data from the original patients enrolled in cohorts 8 and 9, and 20+ weeks of efficacy and safety data on around 40 CSU patients enrolled in the OLE study at 180 mg Q8 weeks. We also plan to include multi-dose data from CIndU patients enrolled in the OLE in the Q1 update, which will consist of 15+ weeks of efficacy and safety results from around 15 CIndU patients. Moving to asthma, as Dan stated, the ETESIAN data provides strong proof of concept for briquilimab's mechanism of action in asthma, with the initial results demonstrating the potential to reduce both airway hyperresponsiveness and the accumulation of eosinophils in sputum, both of which are key factors in managing chronic asthma and reducing exacerbations. Jasper is evaluating next steps to advance briquilimab in chronic asthma, and we plan to provide an update in Q1 of next year. With that, I'd like to open the meeting to questions. Operator? Thank you, Ron, and thank you to our speakers. At this time, we'll be conducting a question-and-answer session. As a reminder to our covering analysts who are joining us live, please raise your hand to indicate you have a question and join the queue. Please hold for a brief moment while we pull for questions. Our first question comes from Yaron Werber at TD Cowen. Please go ahead, Yaron. Great. Thanks so much, and thanks for doing this. We appreciate it. Maybe a couple of questions more, actually, on the first one. Can you give us a little bit of a sense? What should we expect to see Cohort 8 or 9 from redosing and also remind us from your prior CIndU cohorts? Second, just on the asthma, I know it's only obviously a single dose, so we've got to take it with a grain of salt as to what we can, how much clarity we can see here. There's obviously some initial markers of activity. I believe the doubling of the dose for methacholine challenge is considered clinically meaningful, and then between a 10%-20% early to late response reduction in FEV1 is considered clinically meaningful. Can you maybe just put this data in context for us? I know, again, it's a single dose, so it's not obviously enough of an experience. Thank you. Good morning, Yaron, and thank you for the question or questions. Maybe I'll ask Dan to respond to the asthma questions, and then I'll close it out by answering your question around the data in Q1. Dan? Sure. Thank you. Your question has to do with the methacholine response and the reduction in hyperresponsiveness to a single dose of briquilimab. First of all, this is a, as you mentioned, it's a single dose, 180 mg administered to the patients, and then the allergen bronchoprovocation is done six weeks later. We've seen from the briquilimab studies in CSU that the complete suppression of mast cell lasts for about four to six weeks, and we are beginning already to see a return of mast cell by that six-week period of time. We are seeing a significant number of doubling doses of methacholine to cause a 20% reduction in FEV1. Based on the exposure to the patients, this looks as though it is clearly suppressing the hyperresponsiveness induced by the allergen challenge. Further evaluation with multiple doses will be required to fully characterize the response of briquilimab in asthma. Okay. Thank you, Dan. Regarding data in the Q1 update, we will have, as we previously guided, somewhere between 8 and 12 patients that are new patients enrolled into cohorts 8 and 9. That will largely depend on the timing of our data cutoff. In addition to that, importantly, we will have data on the open-label extension study, which is 180 mg Q8 weeks, where the first 11 patients we reported on from that study in July showed a 71% complete response rate at 12 weeks. We are very much encouraged and looking forward to seeing that data, as well as the open-label extension in CIndU, which will be the first time repeat dosing with briquilimab will take place in that patient population. Importantly, as I stated previously, continued follow-up on safety. As Dr. Metz pointed out, we know that the patients in cohorts 8 and 9 very much received active drugs, so we already have a good indication that repeat dosing of 240 mg and patients having all those patients having received at least four doses of 240 or a loading dose of 240 followed by 180, and again, all of those patients having received at least four courses of therapy resulted in a very favorable safety profile. We will look forward to the totality of that data in Q1. Thank you for your questions, Yaron. Our next question comes from Matthew Phipps at William Blair. Please go ahead, Matthew. Good morning, guys. Thanks for taking my questions and providing all this data. Following up on the methacholine PD-20 shift, we're surprised to see such a big difference between challenge one and challenge two, given you see FEV1 benefit and sputum eosinophil reductions right away with challenge one. I'm just surprised there's such a big shift in challenge two. I guess, what could be some possible next steps in asthma? I realize you got to plan this out, but is it just tapping it and now go back and do a multi-dose challenge study, or could you move into more of a moderate asthma patient population? The sample size in this study is small, and I do not think that we have fully characterized the responses that are going to be seen in asthma. In the patients that were treated, we are seeing that mast cell depletion results in a favorable improvement in FEV1 in the early and late asthmatic response, both at six weeks and at 12 weeks. I think what you are seeing is we have depleted the mast cell in the bronchial epithelium, and it takes time for them to return. The clinical effect is, frankly, a little bit longer than I would have expected. I would have expected by 12 weeks, we would have seen closer to a return towards baseline. I am quite favorably impressed with the results, and that needs to be borne out in larger clinical trials. If I can just ask one quick follow-up. Given the difficulties in diagnosing CSU patients, would you ever consider a pivotal trial that included a responder criteria run-in followed by a randomized withdrawal? It's an interesting question. That's not been a traditional approvable study design. CSU, in practice, is, in fact, a clinical diagnosis, and I think we would want to try to replicate clinical practice as closely as possible so that the study results are translatable and as relevant as possible to clinicians. It's something to think about, though. Yeah. Thanks, Dan. Thank you for your questions, Matthew. Our next question comes from Leonid Timashev at RBC. Please go ahead. Hey. Thanks, guys. I just want to follow up on the non-responding patients. I guess, are you surprised that there's no contribution from mast cell depletion in these patients who don't have strictly mast cell-driven disease? I mean, is it possible that higher potency or higher dose could ultimately drive benefit in these patients, as we saw with that one patient who ultimately did respond? I guess, related to that, have you gone back and looked at some of the other non-responders you've had in other past cuts of data, and do you feel that they may have also been non-mast cell-driven, or are there potentially maybe other reasons that those patients hadn't responded? Thanks. Yes. Good morning, Leo. Thank you for the question. We have looked at previous non-responders, and we've had a couple of those. What is very consistent is that we see with briquilimab a deep and consistent reduction in tryptase and generally tryptase that drops below the LLOQ, which would imply that you're having either complete 100% inhibition of total body mast cell or mast cell depletion. What we've seen is that that very much correlates to efficacy. Having said that, I'll ask Dr. Metz to opine that if you're inhibiting the mast cell or you're depleting the mast cell but yet not getting a clinical response, how to interpret that? What's that mean? Yeah. In the end, we can use a highly effective targeted approach for diagnosis of a mast cell-mediated disease. I mean, this is different to what we are usually used to, knowing that a drug never works 100% in any patient. For a mast cell-driven disease, if you achieve mast cell depletion, the disease or signs and symptoms of the disease should be gone. Now, looking at the data we have, I mean, we only have tryptase as a marker for mast cell depletion here because we do not have skin biopsy, which would be wonderful to have, but difficult to do in every patient. Based on the tryptase data, we see a robust reduction in these tryptase levels, indicating that there is at least also a robust reduction of mast cell numbers. Whether it's 100% or less, we don't know, but there's no reason to believe that you can't achieve more by further depleting mast cell. If you already have your tryptase reduction, you can't go beyond that. Increasing doses would not help here. I do believe that the doses that are investigated, the doses that are investigated here are effective doses, even though there might, of course, be individual patients where a late response may occur, for example, if they start out with a higher number of mast cell and a higher tryptase level. Yeah, that's my take on it. Thank you, Dr. Metz. Thank you for your questions. Our next question comes from Silvan Tuerkcan at Citizens JMP. Please go ahead, Silvan. Yeah. Good morning, and thank you for taking my questions. Maybe my first one a little bit on a follow-up on an earlier question around how you can possibly ensure enrollment of mast cell-driven CSU patients as you scale up also with an eye on pivotal trial right in all these different geographies. What about the history per doctor? Would you kind of, how would you crack down on the referrals from outside clinics to centers? Is there any antihistamine levels or prior omalizumab response that you could add in your trial that would realistically tilt kind of the scales to ensure that? I have a quick follow-up on the asthma. Yes. Good morning, Silvan. The KOL panel provided us with some really good guidance here, and a few of those things we already implemented, to your point, as on the referrals. If a patient does not come to a treating center with a full medical history, then we're not permitting them in the study. I think there's a number of things like that, as well as a point that Dr. Metz made earlier about ensuring that we have a larger sample size that would probably wash some of this out. Dr. Metz, maybe you can speak a little bit more about some of the clinical aspects here. Yeah. I especially like the comment on previous omalizumab response. What this would tell you, regardless of whether there was a positive or a negative response to omalizumab, it will tell you that this patient has been seen by a specialist before because only a specialist would prescribe an omalizumab. Knowledge about this, for a patient that was, for example, referred, will provide information on the history of the disease. The patient has a long-standing disease and has been seen by a specialist a couple of times. This makes it more likely that the diagnosis is correct. Other than that, there will always be misdiagnosis, and there has been in the past. When Xolair came onto the market 10 years ago, more than 10 years ago, initially, we said that if a patient does not respond to Oma, then we consider your diagnosis because we knew that there might be misdiagnosis in there. This includes specialists, specialist centers. This will occasionally happen, but you can decrease this substantially by just making sure that you know your patient. If you yourself, I mean, the clinical trial unit does not know the patient, then to make sure that there is a good history indicating that someone who knows chronic spontaneous urticaria has seen patients before, one option would be a patient who was considered for omalizumab, for example. Thank you, Dr. Metz. Yeah. Thank you. And then on the asthma side, it's very early days here, and you do not have repeat dosing data, but you have the CSU data where you're kind of shooting for Q8 weeks. Is that regimen possible in asthma, you think, at this point? Sure. I think omalizumab, which has been used in asthma, is administered every two to four weeks, depending on your IgE concentrations and your body weight. If we were able to administer a highly effective mast cell-depleting drug every two months, I think that would be a huge win, for sure. Great. Thank you. Thank you for your question, Silvan. Our next question comes from Emily Bodnar at H.C. Wainwright. Please go ahead, Emily. All right. Thanks for taking the questions. Maybe just to follow up on the previous question about prior Xolair use, do you have information on those 10 patients and how many of those had previous Xolair use and if they did have it in the past, how they did on it? Do you know the answer to that? Yeah. Thanks for the question. Yeah. Only one patient had prior Oma use, and we do not have the history of their response on omalizumab. Okay. Thank you. On asthma, maybe if you could discuss the reduction in sputum eosinophils and how mast cell depletion kind of could translate to seeing that reduction. Dan? Sure. Sputum eosinophils are a reflection of airway inflammation, and we know that in T2 high asthma in particular, you see an influx of eosinophils into the airway that probably are driven by IL-4, IL-5, IL-13, and other cytokines. They are an indication of exacerbations of asthma. You're seeing them with exacerbation. The reduction of the accumulation of eosinophils in induced sputum really points to the role of the mast cell as essentially the central actor in driving airway inflammation. If we can reduce the mast cell burden in the airway, what we're seeing is a reflection of the reduction of other inflammatory cell infiltrates, whether that's going to be the eosinophil or neutrophils or other cells. To me, it's a very encouraging sign. The reduction of airway hyperresponsiveness speaks to control of chronic asthma. The reduction of eosinophils in the sputum speaks to the possibility that you're going to see a reduction in the exacerbation rates in patients with chronic asthma. Emily, I'd just add to that that prior to this study, it was known that mast cell plays the pivotal role in the release phase in asthma, releasing histamine, prostaglandin, and D2. It was also known that mast cell are involved in the recruitment phase, but because no one had ever been able to drug the lung mast cell previously, it wasn't clear that central role that Dan just described. Now it's very clear that mast cell plays a pivotal role in that recruitment phase in asthma as well. Great. Thank you. Thank you for your questions, Emily. Our next question comes from Justin Zelin at BTIG. Please go ahead, Justin. Thanks for taking the question. I wanted to ask, given that misdiagnosis is inevitable here, some misdiagnosis, I just was curious what is typically the misdiagnosis rate seen in the field and if you can build that into further clinical studies as an assumption so that you could statistically power your studies so that it won't distort the efficacy signal here. Sure. Thank you, Justin. We have contemplated that, and we have looked at other clinical trials. Let me hand this off to Dr. Metz, and then I'll circle back. Yeah. The problem is that it's not too easy. The main misdiagnosis for sure is urticaria vasculitis. There are ongoing investigations in better understanding the overlap between prior spontaneous urticaria and urticaria vasculitis, which is there. In some of these patients, there are features of urticaria vasculitis, but it's still CSU. For others, it's completely mast cell-independent, full-blown urticaria vasculitis. There are features that are also in the management algorithm of chronic spontaneous urticaria to rule out this differential diagnosis. This is mostly the duration of the wheals. If a patient has wheal duration of longer than 24 hours, then this is indicative of urticaria vasculitis. The problem is you will not be able to check for this in the office. You have to rely on what the patient is telling you. This is something that is difficult to control for. The other thing or what you would do if you hear from a patient wheal lasts on average longer than 24 hours is taking a biopsy of this wheal. Then you do see in the biopsy the features of urticaria vasculitis. Again, this is not something that you would do to verify the diagnosis in every patient. In the end, it does go through the it's a numbers game. You will always have some patients, and you have to count for those that you might have some misdiagnosed patients in the trial. Ron, I mean, if you have some other thoughts on it. Yeah. Thank you, Dr. Metz. Just adding to that, and Dr. Metz's prepared remarks and our analysis of data sets would suggest that 25% or so of the patients probably that are currently "diagnosed" as CSU probably don't have that. When you look at other clinical trials with whether it's Remi, Dupi, Barzo, their data, while they've never specifically spoken to non-responders, their data would imply that similar type of percentage. I think to Dr. Metz's last comment, it becomes a numbers game. If you have the profound efficacy that we've demonstrated previously, then we can control for that by just ensuring that we enroll enough patients that do have CSU. Again, you can look at the other clinical trials that have done the same, so. Got it. Okay. Great. And then just on asthma, maybe if you could just talk to how you view mast cell depletion offering advantages that other biologics for asthma currently do not provide. Dan? I mean, it's an interesting question, and I think we're so early into the development of this drug for the treatment of asthma, I'm not sure that we have a real clear answer right yet. I have always thought that the mast cell is the central actor that drives the whole inflammatory cascade in the airway. As an allergist, I've just seen so much allergen-induced asthma over the years. I think that if you target the mast cell, you're likely to have a profound effect on allergic asthma for sure. Because of the centrality of the mast cell in the whole asthmatic clinical picture, it does raise an important question of whether or not this is going to work in non-allergic asthma. Given that the mast cell is common to both forms of asthma, I think that there's some real encouraging signs that this could be effective in not only T2 high asthma but also in T2 low asthma. That's something that just will need to be investigated in future clinical trials. Thanks for taking the questions. Thank you, Dan. Thank you for your questions, Justin. I'll now turn it over to Ron to close out the call. Great. Again, thank you all for making time today. We're very encouraged by the strong proof of concept data in asthma, validating that briquilimab can drug the lung mast cell, and more importantly, validating the clinical relevance of drugging the mast cell in this important disease and a very large market opportunity and one that has certainly garnered a lot of interest from the strategics. We are also very encouraged by the safety data we now have at high dose, multi-dose, repeat dosing of 240 mg and 240 followed by 180 mg. Important to note, and we'll provide much more of a safety update and focus on this in Q1, but important to note that to date, we've only seen one grade 3 neutrophil decrease in the entire BEACON study. That includes the data we now have with patients receiving four doses of 240 or 240 followed by three doses of 180. Now that we have the investigation closed and behind us, moving to the turn of the calendar year, we will be able to focus on the new clinical data and a large trove of data that will be coming in Q1 that will enable us then to select our dose to move into our phase IIb study that we are guiding that we would initiate sometime mid-next year. With that, I would like to thank Dr. Metz and all of the other participants in the clinical trials and wish everyone a happy holidays. Thank you.