Jasper Therapeutics (JSPR) Earnings Call Transcript & Summary

Thank you for standing by. Welcome to the Jasper Therapeutics Data Update Webinar. [Operator Instructions] 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 Charite 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, many 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 in the accompanying slides, our most recent Forms 10-K and 10-Q and the reports that we filed or may file on 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 with a drug lot A34954, which was the first time it was introduced into the BEACON study. Two of the 3 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 discussing today are Cohort 8, in which the patients were administered 240 milligrams of briquilimab every 8 weeks. In Cohort 9, we're -- a loading dose of 240 milligrams was given followed by 180 milligrams every 8 weeks. We enrolled a total of 17 patients across 2 cohorts, 13 received active drug and 4 received placebo. Of the 13 patients receiving active drug, 3 were enrolled at sites in the EU, 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 with Cohort 6 which evaluated a single dose of 240 milligrams. While Cohort 6 did achieve high -- slightly higher Cmax 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 lot used in 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 2 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 supply chain from 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 in 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 and foresight or patient insight 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 1 new clinical site that enrolled 5 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. Yes. So I'm a clinician investigator that -- 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. So this is basically summarizing the data that I will present in the next slide on the cohorts 8 and 9. And you see that as part of the internal investigation, the patients in the BEACON cohorts 8 and 9 were switched to the new lot during the 24-week dosing period. So this 54 lot was then replaced at all clinical sites with the 55 lot that was used and is used in the open-label extension. And 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 2 doses with the initial lot. Moving to the next slide. So this is basically showing it all, I think, because it does show that the lot and question was doing what was supposed to be doing, and that is depleting mast cells. So we're 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. So 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 [Audio Gap] the orange line, the 240-milligram single dose stays the same after the lot was changed to the 34955 lot. So this was consistent also in the efficacy with this -- well, unexpected reduced efficacy that for me would be supportive that the patients were looking here that 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, so with 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. So this is a late responder something that we do see in clinical trials, including KIT targeted clinical trials. Taken together, this clearly states that, as I said before, the drug was doing what we're supposed to be doing. So the KIT mediated depletion of mast cells by looking at the reduced tryptase levels clearly show that -- that 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. And 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. And this is unchanged by the way for the 2 different lots. And this is also true for the KIT related safety data, where we do see low rates of hair color changes. We don't see anything skin discoloration. We do see taste change and neutrophil count decrease. So in the rates that we have seen before, so this further shows that the drug at questioned was and is doing what it was supposed to be doing. So to conclude these investigations. I'm really confident to say that the -- I call it weird or anomalous efficacy does really not appear to be the result of an issue with the study drug or with the study conduct. There were no issues, deviations, as mentioned by Dan, and the redosing of the cohort 8 and 9 patients did not drive a different outcome in efficacy nor in safety. And as mentioned before, there were no protocol deviations, issues with site training and so on and so forth. So we and I personally also to think and convinced that this unexpected efficacy results is largely to be the result of patient selection or 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 that 9 out of the 10 patients that did not show any response, the period to have not have chronic spontaneous urticaria. So no mast cell-driven disease. Now this does happen and it for sure has happened in basically every larger clinical trial before it's chronic spontaneous urticaria is a disease that is diagnosed based on the clinical experience. So there is the possibility that there are patients in there that do not have CSU, but, for example, urticaria and vasculitis that is mast cell mediated. And it's likely that these patients are also have been included in other studies, where they have also been nonresponders even though we can't give concrete numbers on this. The solution from this either 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, and our recommendation is to have a certified immunologist or dermatologists who knows CSU. That means he or she should have a history of diagnosing, but also treating chronic spontaneous urticaria patients. And maybe also an expanded review of patient's history during this study can help making the right diagnosis, including visual records of lesions on smartphones. And in the end, of course, as always, larger sample size will certainly mitigate an impact of non-mast cell chronic 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 assess changes in the early asthmatic response, as well as the airway hyperresponsiveness to a methycholine 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-milligram dose of briquilimab in patients with the 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 6 -- week 6 allergen challenge assessment, 8 were on active drug, 6 on placebo. This slide shows the effects of briquilimab on serum tryptase levels. A single 180-milligram dose of briquilimab resulted in serum tryptase reductions at 6 weeks which is similar to this tryptase reductions observed at 180 milligrams with briquilimab in BEACON, spotlight and our chronic urticaria open-label extension study. Looking at the FEV1 response following allergen challenge at baseline in 6 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 delayed asthmatic response. On the next slide, we see that we have 2 example patients showing the effect of briquilimab -- showing the effect that briquilimab can have on early and late asthmatic responses. These patients were 2 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 6 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 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 in 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 hyper-responsiveness. This study shows for the first time that a potent 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 will be the efficacy and safety data on additional patients enrolled in the BEACON study as well as 24-plus weeks of safety data from the original patients enrolled in cohorts 8 and 9, and 20-plus weeks of efficacy and safety data on around 40 CSU patients enrolled in the OLE study at 180 milligrams 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-plus 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 in the accumulation of eosinophils and 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. [Operator Instructions] So our first question comes from Yaron Werber at Cowen.

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 in Q1 from cohort 8 or 9 from redosing and also remind us from your prior [ CIndU ] cohorts? And then second, just on the asthma. I know it's only obviously a single dose. So we 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, which is considered clinically meaningful and then between 10% to 20% early to late response, reduction in FEV1 is considered -- FEV1 is considered clinically meaningful. So 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.

Yaron, thank you for the questions. Maybe I'll ask Dan to respond to the asthma questions, and then I'll close it up by answering your question around the data in Q1. Dan?

Thank you. So your question has to do with the methacholine response and the reduction in hyper responsiveness to a single dose of briquilimab. First of all, this is a -- as you mentioned, it's a single dose, 180 milligrams, administered to the patients. And then the allergen bronchoprovocation is done 6 weeks later. We've seen from the briquilimab studies in CSU that the complete suppression of mast cells lasts for about 4 to 6 weeks. And so we're beginning already to see a return of mast cells by that 6-week period of time. We are seeing a significant number of doubling doses of methacoline to cause a 20% reduction in FEV1. And 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.

Thank you, Dan. And 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 milligrams Q8 weeks where the first 11 patients we reported on -- from that study in July, showed a 71% complete response rate at 12 weeks. So we're 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. And 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 milligrams and patients having -- all those patients having received at least 4 doses of 240 or a loading dose of 240 followed by 180. And again, all of those patients having received at least 4 courses of therapy resulted in a very favorable safety profile. So we'll look forward to the totality of that data in Q1.

Our next question comes from Matthew Phipps at William Blair.

Following up on the [indiscernible] point shift. Are you surprised to see such a big difference between Challenge 1 and Challenge 2 given you see everyone benefit and sputum eosinophil reductions right away with Challenge 1. We surprised that it's such a big shift in Challenge 2. And then I guess what could be some possible next steps in asthma. I realize you got to point this out, but is it just happen to now go back and do a multi-dose challenge study? Or could you move into more of a moderate [indiscernible] patient population?

Dan?

So the sample size in this study is small. And so I don't think that we have fully characterized the responses that are going to be seen in asthma. The -- the patients that were treated, we're seeing that mast cell depletion results are favorable improvement in FEV1 in the early and late asthmatic response, both at 6 weeks and at 12 weeks. I think what you're seeing is the -- we've depleted the mast cells in the bronchial epithelium and it takes time for them to return. And so 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. So I'm quite favorably impressed with the results, and that needs to be borne out in larger clinical trials.

If I can just ask 1 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 -- but 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.

Next question comes from Leonid Timashev at RBC.

I just wanted to follow up on the nonresponder patients. I guess -- are you surprised that there is 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 ultimately did respond. And I guess related to that, have you gone back and looked at some of the other nonresponders 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 may be other reasons that those patients hadn't responded?

Yes. Leo, thank you for the question. So we have looked at previous nonresponders 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 should imply that having either complete 100% inhibition of total body mast cells or mast cell depletion. And 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 when you're depleting the mast cells, but yet not getting a clinical response, what -- how to interpret that? What's that mean?

Well, in the end, we can use a highly effective KIT-targeted approach for diagnosis of mast cell mediated disease. So I mean, this is different to what we are hugely 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 don't have skin biopsy, which would be wonderful to have, but difficult to do in every patient. But based on the tryptase data, we see a robust reduction in these tryptase levels, indicating that there's at least also a robust reduction of mast cell numbers, whether it's 100% or less, we don't know. But there is no reason to believe that you can achieve more by further depleted mast cells. If you already have your tryptase reduction, you can't go beyond that. So increasing doses would not help here. So I do believe that doses that are investigated -- doses that are investigated here are effective doses, even though there might, of course, be individual patients where late response may occur, for example, if they start out with a higher number of mast cells in the higher tryptase level. But -- yes, that's my take on it.

Our next question comes from Silvan Tuerkcan at Citizens JMP.

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? Like would you kind of like -- how would you crack down on the referrals from outside clinics to centers? And 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? And then I have a quick follow-up on the asthma.

Yes. So, the KOL panel provided us with some really good guidance here. And a few of those things we already implemented, to your point is 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. So I think there's a number of things like that and 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. But Dr. Metz, maybe you can speak a little bit more about some of the clinical aspects here.

Yes. So I especially like the comment on previous omalizumab response, the -- what this would tell you, regardless of whether there was any positive or a negative response from omalizumab, it will tell you that this patient has been seen by a specialist before, because only the specialist would prescribe an omalizumab. So knowledge about this for a patient that was, for example, referred, will provide information on the history of the disease. So the patient has a long-standing disease and has been seen by a specialist a couple of times. So 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 on to the market 10 years ago, more than 10 years ago, initially, we said that if a patient does not respond to oma then reconsider your diagnosis because we knew that there might be misdiagnosed in there, and this includes specialists, specialist centers. So this will occasionally happen, but you can decrease this substantially by just making sure that you know your patient. And 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.

And then on the asthma side -- it's very early days and you don't 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?

Dan?

Sure. I think omalizumab, which has been used in asthma is administered every 2 to 4 weeks, depending on your IgE concentrations in your body weight. And so if we were able to administer a highly effective mast cell depleting drug every 2 months, I think that would be a huge win for sure.

Our next question comes from Emily Bodnar at H.C. Wainwright.

Maybe just a follow-up on the previous question about prior omalizumab use. Do you have information on those 10 patients and how many of those had previous omalizumab use? And if they did have it in the past, how they did on it?

Do you know the answer to that?

Yes. Thanks for the question. Only 1 patient had prior oma use. We don't have the history of their response on omalizumab.

Okay. And 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. So 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. And so the reduction of the accumulation of eosinophils and induced sputum really points to the role of the mast cell as essentially the central actor in driving airway inflammation. And 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. And so 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.

And Emily, I'd just add to that, that prior to this study, it was known that mast cells play the pivotal role in the release phase in asthma, releasing histamine prostaglandin R2. It was also known that mast cells are involved in the recruitment phase, because no one had ever been able to drug the lung mast cells previously it wasn't clear that central role that Dan just described. And now it's very clear that mast cells play a pivotal role in that recruitment phase in asthma as well.

Your next question comes from Justin Zelin at BTIG.

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 that you could statistically power your study so that it won't distort the efficacy signal here?

Sure. Thank you, Justin. So we have contemplated that and we have looked at other clinical trials. So let me hand this off to Dr. Metz, and then I'll circle back.

Yes. The problem is that it's not too easy. So the main misdiagnosis for sure, is urticaria vasculitis. And there is ongoing investigations and better understanding and the overlap between chronic spontaneous urticaria and urticaria vasculitis, which is there. So in some of these patients there are features of the urticaria vasculitis, but it still CSU. And for others, it's completely mast cell independent full-blown urticaria vasculitis. And of course, there are features that is also in the management algorithm of chronic spontaneous urticaria to rule out this differential diagnosis. And this is mostly the duration of the wheels. So if a patient has wheel 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. So you have to rely on what the patient is telling you. And so this is something that is difficult to control for. The other thing or what you would do if you hear from a patient will last on average, longer than 24 hours is taking a biopsy. And then you do see in the biopsy the features of urticaria vasculitis. But again, this is not something that you would do to verify the diagnosis in every patient. So in the end, it does go through the -- it's numbers game. You will always have some patients, and you have to account for those that you might have some misdiagnosed patients in the trial. But Ron, I mean, if you have some other thoughts on it.

Thank you, Dr. Metz. Just adding to that in Dr. Metz' prepared remarks and our analysis of data sets would suggest that 25 or so percent of the patients probably that are currently "diagnosed CSU" probably don't have that. And when you look at other clinical trials with whether it's Remi, Dupi, Barzo and their data while they've never specifically spoken to nonresponders, their data would imply that similar type of percentage. And I think to Dr. Metz' last comment, it becomes a numbers game. And 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 and again, you can look at the other clinical trials that have done the same.

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 don't 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 just seen so much allergen induced asthma over the years. And 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 and the whole asthmatic clinical picture, it does raise an important question of whether or not this is going to work in nonallergic asthma. And given that the mast cell is common to both forms of asthma, I think that there is some real encouraging signs that this could be effective in -- not only T2-high asthma but also in T2-low asthma, and that's something that just will need to be investigated in future clinical trials.

I'll now turn it over to Ron to close out the call.

Great. Well, 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 in 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 milligrams -- 240 followed by 180 milligrams. And important to note, and we'll provide much more of a safety update and focus on us in Q1. But important to note that to date, we've only seen 1 grade 3 neutrophil decrease in the entire BEACON study, and that includes the data we now have with patients receiving 4 doses of 240 or 240 followed by 3 doses of 180. And now that we have the investigation closed and behind us, moving to the turn of the calendar year, we'll 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're guiding that we would initiate sometime mid next year. So with that, I'd like to thank Dr. Metz and all of the other participants in the clinical trials, and I wish everyone a happy holidays. Thank you.