Thank you for standing by, and welcome to the Jasper Therapeutics KOL Webinar. At this time, all attendees are in a listen-only mode. A question-and-answer session will follow the formal presentations. If you'd like to submit a question, you may do so by using the Q&A text box at the bottom of the webcast player or by emailing your questions to questions@lifesciadvisors.com. 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 Head of Investor Relations, Alex Gray. Please go ahead, Alex.
Thank you, Tara, and thank you to those listening in today. Joining us for the prepared remarks are Dr. Joshua Boyce, the Albert L. Sheffer Professor of Medicine in the field of allergic diseases at Harvard Medical School. And from Jasper, Ron Martell, CEO, Dr. Wendy Pang, SVP, Research and Translational Medicine, and Dr. Ed Tucker, CMO. Also on the line is Herb Cross, Chief Financial Officer, who will be available during the Q&A session. Due to other commitments, Dr. Boyce and Dr. Tucker will not be able to participate in the Q&A. During today's events, 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 in the accompanying slides, our most recent Forms 10-K and 10-Q, and the reports that we may file on Form 8-K with the Securities and Exchange Commission. All our statements are made as of today, May 20, 2024, based on information currently available to us. We can give no assurance that these statements will prove to be correct. 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 turn over the call to Ron Martell. Ron?
Good morning, and thank you, Alex. I'm Ronald Martell. I'm the CEO of Jasper Therapeutics, and on behalf of Professor Boyce and all of my colleagues at Jasper, I'd like to welcome you to the Jasper KOL webinar. To summarize and provide an overview of the announcement that we made last week regarding our intent to develop briquilimab in asthma. For today, we'll start with Dr. Wendy Pang, who will provide us with an overview of mast cells in asthma and a review of the preclinical data with briquilimab. We'll then turn the call over to Professor Boyce, who will talk about the current treatment landscape and the need for a new and better asthma treatments. Finally, Dr. Edwin Tucker will provide us with an overview of the clinical development program for briquilimab in asthma.
As many of you on the call are likely aware, mast cells are potent drivers of the inflammatory response in the skin, the lung, and the gut. Mast cells, however, are fairly primitive in their role in the immune system, specifically when in the skin, and protect from things like venom or parasitic infections. Mast cells are largely triggered by allergens and other irritants that cause mast cells to degranulate. For this reason, we think that having the ability to safely deplete mast cells could lead to significant clinical benefit for patients in a variety of diseases. Our lead program, briquilimab, is an aglycosylated IgG1 antibody targeting c-Kit. Importantly, when briquilimab binds to c-Kit on the surface of mast cells, we shut down all activity in that cell, thereby making certain that those mast cells no longer degranulate.
This is important whether we're talking about mast cells in the skin or when we're talking about mast cells in the lung for asthma, like we will today. Importantly, it certainly appears as if we can deplete these mast cells, and when they're depleted, the durability of that opportunity is significant and may be longer than three months. We think that briquilimab is the definition of a portfolio in a product, and we've looked at a number of different diseases. We've taken better part, the better part of this last year to evaluate what should our next opportunity be here beyond the urticarias. As you know, we're conducting two ongoing clinical trials, the BEACON and the SPOTLIGHT studies in CSU and inducible urticarias.
As we explored the opportunity for what is the next indication, it was really important for us to anchor this in the biology of the mast cell and to really understand the clinical opportunity here. For that reason, we conducted our own internal research with the Jasper mouse, and you'll hear more about that, and looking at mast cells in airways. In addition to that, there are two significant bodies of clinical data here looking at imatinib and masitinib, that we fully now understand the role of the mast cell, and provided us with a strong clinical rationale for developing briquilimab in the asthma setting.
Lastly, certainly, and you'll hear this from Dr. Boyce, that there's a significant unmet medical need in this setting. With that, I'd like to turn the call over to Dr. Wendy Pang. Wendy?
Thanks, Ron. So we know, based on a significant body of data from the last several decades, that mast cells play an important role in the allergic inflammation and tissue remodeling that occurs in asthma. Mast cells are found throughout the lung, and they can respond to a vast multitude of triggers, including environmental allergens, which then leads to the release of cytokines and other mediators of inflammation, which then, in turn, help to drive a wider inflammatory response that includes recruitment of other innate and adaptive immune system cells, stimulation of the nervous system, an increase in vascular permeability, crosstalk with fibroblasts, et cetera. And this chronic inflammation that occurs in asthma leads to airway tissue remodeling.
Shown on the left, the lungs of patients with asthma, the level of tryptase, which can be used as a biomarker for mast cell burden, increases with the severity of disease, demonstrating that elevated mast cell numbers in the lungs are correlated with disease burden. In patients with severe asthma, tryptase is not only significantly elevated in the lungs but also in blood plasma, reflecting a significant mast cell burden in these patients. Importantly, mast cells are an innate immune cell, and they interact with multiple adaptive immune system pathways. As shown on the right, elevated tryptase in the lungs, indicating increased mast cell burden, has been observed in severe asthma patients across different subtypes, suggesting that mast cells play an important role in asthma independent of Type 2 inflammation status.
Briquilimab is a humanized, aglycosylated monoclonal antibody that binds to c-Kit and potently and specifically blocks the binding of its ligand stem cell factor, thus depriving mast cells of their key survival signal. Briquilimab's ability to fully and potently inhibit c-Kit signaling leads to mast cell apoptosis. More importantly, because briquilimab is aglycosylated, briquilimab binding to mast cells does not cause mast cell degranulation, nor does briquilimab recruit immune cells via Fc receptors that may cause mast cell degranulation as well. After briquilimab is cleared from the body, c-Kit signaling is restored. We've evaluated briquilimab in over 100 people to date, and briquilimab has been well tolerated with no serious drug-related adverse events to date. At Jasper, we have developed a novel mouse model to directly be able to evaluate briquilimab in vivo in multiple disease settings.
This mouse has been engineered such that the usual mouse c-Kit extracellular domain has been replaced with the human c-Kit extracellular domain. Using this mouse model, which retains normal c-Kit signaling, we can directly test briquilimab instead of having to use mouse antibody analogues that would be different from the clinical antibody. One such disease model that we've developed using the Jasper c-Kit mouse is in asthma. Using the gold standard asthma animal model, we can induce disease in this Jasper c-Kit mouse by exposing them to cockroach antigen. We then treat animals with either placebo or a single dose of briquilimab, which is approximately equal by allometric scaling to the human doses we're using. A few days to weeks later, we evaluate the animal's lung function as well as lung pathology.
So here on the top left, you can see healthy PBS control animals that were not induced to develop asthma. They have few mast cells in the lungs. In contrast, the lungs of animals that are induced to develop asthma, which is shown on the top right panel on the left side, have a significantly higher mast cell burden. However, in animals with asthma but treated with a single dose of briquilimab, mast cell numbers are significantly reduced, and this is shown on the bottom left. Importantly, lung function testing in these animals showed that briquilimab-treated as, asthmatic animals, which are indicated by the blue lines, had significant improvement in pulmonary resistance following methacholine challenge, and this is in contrast to the placebo-treated asthmatic animals indicated by the red line.
Notably, the lung function after just a single dose of briquilimab approaches that of normal, healthy, non-asthmatic animals, indicated by the black lines. We're planning to submit these findings, as well as additional, evaluations we've done in this mouse model, for a manuscript to be published hopefully later this year. In addition to Jasper's c-Kit mouse model, briquilimab-driven mast cell depletion has also been observed in non-human primates. African green monkeys administered weekly briquilimab for one month showed a dose-dependent decrease in mast cells in the lungs. Taken together, these preclinical or nonclinical data suggest that the mechanism of mast cell depletion by c-Kit signaling blockade is conserved across mammalian species, and we can leverage this mechanism to address diseases such as asthma.
With that, I'd like to introduce Dr. Joshua Boyce, Chief of the Division of Allergy and Immunology at the Brigham and professor at Harvard Med School. He was also principal investigator on a recent clinical trial evaluating the tyrosine kinase inhibitor imatinib in asthma patients. Dr. Boyce?
Well, thank you, Wendy. So I'm going to talk about current treatments and unmet need in asthma. And really, since 1991, with the publication of the NHLBI guidelines for the diagnosis and management of asthma, asthma management has really focused on treatment of the disease as an inflammatory process, with inhaled glucocorticoids, and with the addition of long-acting beta agonists, for control of asthma not adequately responding to steroids alone. But even with those strategies, there's still a substantial fraction of the asthma population who have moderate to severe disease, and yet do not achieve adequate control with existing conventional treatments.
And this led to the development of the biologics, and we now have five different monoclonal antibodies that are directed against, cytokines, cytokine receptors, and IgE, all of which have mechanistic, relationships to the asthma pathophysiology. And currently, it's estimated that there are about 2.5 million biologic-eligible patients with severe asthma in the US and European Union, and of those, approximately 300,000 are currently receiving, biologics. And these biologics have, significantly improved outcomes from asthma, in patients with severe disease, as I'll, explain in a couple of slides. So when we talk about severe asthma, we are not talking about a single disease entity.
In fact, even the designations of Type 2 high asthma and Type 2 low asthma are probably vast oversimplifications, and within each category are probably subgroups of asthma, not all of which we are currently able to characterize. When we talk about Type 2 high asthma, we're talking about asthma that is associated with persistent evidence of Type 2 cytokine actions that produce eosinophilia, IgE synthesis, and sensitization to antigens. And within the Type 2 high group, we can identify individuals who have persistently elevated blood eosinophil counts, usually defined as in excess of 150 eosinophils per cc or 300 eosinophils per cc, depending on the study. We have patients who have both blood eosinophilia and are allergic, as evidenced by positive skin tests or positive specific IgE tests to common inhaled allergens.
Then we have individuals who lack blood eosinophilia but do have positive skin tests. So all three of these groups sort of fall under the Type 2 high designation. There are several biomarkers used, either clinically or in research protocols, to identify patients with Type 2 high asthma. These include elevated exhaled nitric oxide, a reflection of inducible nitric oxide synthase in the airways, high serum IgE, elevated serum periostin, and high blood or sputum eosinophil counts. Again, all of these are reflections of the actions of Type 2 cytokines. The Type 2 low group is really sort of a default designation when patients who have severe asthma lack these indices of Type 2 high disease. There really is no single accepted biomarker by which you can categorize a patient as Type 2 low.
So we basically rely on the absence of the Type 2 high markers. Patients with Type 2 low asthma may have neutrophil accumulation in the airways that can be measured by sputum neutrophil counts. But it's important to note that even patients with eosinophilic Type 2 high asthma often also have a lot of neutrophils. It's just that they have the eosinophils, whereas the Type 2 low group does not. Type 2 low asthma may be associated with high TNF levels in the BAL fluid or high levels of YKL-40, which is a human ortholog of chitinase in the mouse, that can be measured in the blood. But none of these are well standardized. So basically, Type 2 low is sort of a wastebasket diagnosis, where patients lack Type 2 high indicators but still have severe disease.
When we think about breaking apart severe asthma into these Type 2 high and Type 2 low categories, we can see from this slide where the placement of the currently available respiratory biologics fall. For patients who have blood eosinophilia, both with and without positive skin tests, the biologics that target interleukin 5 or the interleukin 5 receptor are clinically indicated because IL-5 and IL-5 receptor is important for the development of eosinophilic inflammation in the lung. Dupixent, which targets the IL-4 / IL-13 receptor alpha, is approved also for eosinophilic asthma, both with and without allergy. Tezspire, which is an antibody against thymic stromal lymphopoietin, is effective for eosinophilic asthma as well.
As you begin to move across the spectrum here, you can see that when patients are allergic and have positive skin tests, they're also eligible to receive Xolair, which is a monoclonal against immunoglobulin E. Now, when you start to think about patients who are Type 2 high but don't have eosinophilia, just have positive skin tests, the therapeutic options start to diminish, and you're left only with Xolair and Tezspire. Then when you talk about Type 2 low asthma, the only biologic to date that has demonstrated any efficacy at all is Tezspire. So effectively, what this means is about half of all patients with severe asthma really have limited options in terms of treatments that can be administered if they are essentially uncontrolled on conventional glucocorticoid therapy with long-acting beta agonists.
Now, this slide shows you again, the labeled indication for each biologic, kind of what we went through in the previous slide, the dosing regimen and the annualized exacerbation risk reduction. And this tends these days to be the principal outcome that clinical trials target when they are looking at outcomes in patients on biologics who have severe asthma. And that's because the exacerbation rate is important, but it's also because, to date, there really haven't been standardized treatments for asthma that have significant impacts on airway hyperresponsiveness, the sensitivity of the lower airways to methacholine, which tends to be relatively fixed.
Now, a few years ago, this study, called the KIT In Asthma or KIA study, was published in the New England Journal of Medicine, and this was really a proof of concept study based on the fact that in severe asthma, refractory to treatments, there's an expanded population of mast cells in the airway epithelium, as well as in the airway smooth muscle, and the numbers of these mast cells correlate with airway hyperresponsiveness. This trial was set up with the primary outcome being a change in airway hyperresponsiveness to methacholine. As you can see in the left-hand figure here, treatment with imatinib, the KIT inhibitor, actually did impact airway reactivity with increases in PC20, which means an increased concentration of methacholine was necessary to elicit a given change in lung function.
You can also see that there's a trend toward an increase at 6 months in the placebo group, which probably reflects the fact that these carefully monitored patients were faithful to their inhaled glucocorticoids during the clinical trial. And on the right, you can see the serum tryptase levels decreased by about 40%, indicating that the imatinib had hit its target. And this 40% reduction is essentially the same magnitude of effect that was seen in bronchial biopsies on the numbers of mast cells. So this KIT inhibitor is not a mast cell ablative drug. Rather, it attenuates mast cell numbers and probably impacts their ability to be activated. Now, adding further fuel to the fire, that inhibiting mast cells may be therapeutically efficacious is this phase III study of masitinib, which is another KIT inhibitor.
And what you see here is the primary outcome is a reduction in exacerbations. So unlike the KIA study, where the primary outcome was a change in airway hyperresponsiveness. You can see that there's a fairly consistent reduction in exacerbations across essentially all patient groups who were enrolled in this study. It's very important to note that both the KIA study and the masitinib phase III study showed essentially equivalent degrees of efficacy in patients who had Type 2 high indices and patients who had Type 2 low indices. This is very important because, as I said, the options therapeutically for patients with type 2 low disease are really quite limited. Now, at the moment, there is a large multi-centered adapt, adoptive—s orry, adaptive clinical trial sponsored by the National Heart, Lung, and Blood Institute, which includes an arm using imatinib to target the KIT receptor.
And in this case, they are specifically targeting patients who have blood eosinophil counts less than 300 per microliter, which would put them into the Type 2 low category. And that is based on the observations made in the KIA trial, that Type 2 low patients do tend to respond well to the KIT inhibitor. But that study, of course, was underpowered to detect a change in exacerbations. The PrecISE trial is much larger and better powered. So to sort of summarize what I've said here, severe asthma patients have significant unmet needs that may be broadly addressed by KIT inhibitions, which in all likelihood, is working by depleting tissue mast cells.
New treatments are needed for patients with severe asthma. Preclinical evidence that targeting the mast cell reduces the asthmatic response is compelling, and these two clinical trials that I talked about show that KIT inhibition improves airway hyperreactivity, reduces exacerbations, and improves lung function as well. Mast cell depletion may lead to broad therapeutic benefit in asthma patients across endotypes. This brings to mind the possibility that an asthma challenge study design is appropriate proof of concept to evaluate the clinical potential of briquilimab. With that, I'm now going to turn it over to Dr. Ed Tucker to talk about briquilimab clinical development. Thank you for your attention.
Thank you, Professor Boyce. I'm now going to talk about briquilimab clinical development program. One of the key features of briquilimab is the design and characteristics to enable an optimal biologic dosing approach for diseases driven by mast cells. On the left-hand side of the picture here, you'll see we begin with dosing briquilimab to a threshold which initiates depletion of the mast cells—b riquilimab binds to the c-Kit receptor, initiating the apoptotic process, which drives down the population of mast cells, which are then phagocytosed over a period of time, relieving both the mast cells in the tissue and potentially the relief for patients. During that time, the drug is cleared from the body and thus giving a drug-free interval of several weeks for c-Kit signaling to return in other c-Kit-expressing cells.
Now, we follow the biology here, so as mast cells take about three months or longer to recover, we're setting our clinical program on redosing schedules, which match the biology. And in doing so, we think that we can enhance the durability of effect while minimizing the safety concerns of those other c-Kit-expressing tissues. And we'll continue to dose the patients on this schedule, maintaining the effect. And so we've demonstrated, as Dr. Pang and Professor Boyce have shown, that c-Kit inhibition can drive down the populations of mast cells in several tissues, as shown in several different models. Here on the right-hand side, we're showing our healthy volunteer data, where we show a really nice dose-response curve. As we escalate or increase the dose of briquilimab in the healthy volunteers, we see an increasing reduction in mast cell depletion.
And this mast cell depletion was shown to occur as early as seven days, consistent with the earlier discussions around mast cell depletion and the effects of c-Kit inhibition. This basically shows that we have consistency across several animal models, but also several tissue models as well. And this is the foundation of our entire clinical development program, which was started with the urticaria program. And here we're looking to eliminate the mast cells from the skin, which is a perpetrator of the diseases of urticaria. CSU and CIndU are being tested in two studies. The first is the BEACON study, which we began enrolling in the latter part of last year, and we look forward to sharing our data in the third quarter of this year. And similarly, we're testing briquilimab in a single-dose study in chronic inducible urticaria, two types, chronic cold urticaria and symptomatic dermatographism.
We look forward to sharing data from that study in the second half of this year. That leads me to the next indication, which we've talked about earlier today from Professor Boyce, which is our challenge study in asthma. This is a phase I-B/II, which we anticipate will demonstrate the proof of concept of mast cell depletion in asthma with a therapeutic dose of subcutaneous briquilimab, which will inform for future studies. We want to demonstrate the safety and efficacy of the therapeutic in a new indication, that being asthma. We feel that the challenge study is, has a high predictive value for future trials. We want to assess the early and late asthmatic response, as well as the airway hyperresponsiveness, which Professor Boyce mentioned earlier, following the briquilimab administration.
Our study design is intended to be efficient, enabling rapid advancement into later-stage studies. We're really excited at Jasper that we anticipate that our first patient into the study will be by the fourth quarter of this year. Thank you for your attention, and I'm now going to hand over to Ronald Martell.
Thank you, Ed. In summary, we believe that mast cell depletion via briquilimab offers a novel therapeutic approach with potential to address unmet medical need for asthma. Early-stage disease in asthma is driven by mast cell degranulation. Reduction of inflammation by mast cell depletion may reduce excess inflammation and epithelial remodeling. As with urticaria, mast cell depletion may lead to a durable effect based on long periods of mast cell recovery, lasting days to months. Finally, c-Kit may have an impact across multiple disease endotypes. In conclusion, 2024 has been and will continue to be a transformational year for Jasper with our launch of the development program in asthma, in addition to the key clinical readouts from our urticaria program. We look forward to providing further updates as our programs advance. With that, I'd like to open the meeting to questions. Operator?
Great. Thank you, Ron. At this time, we'll be conducting a question-and-answer session with our speakers. If you'd like to submit a question, you may do so by using the Q&A text box at the bottom of the webcast player or by emailing your questions to questions@lifesciadvisors.com. Please hold for a brief moment while we pull for questions. Our first question comes from Jeanna Han at Cowen. Please go ahead, Jeanna.
Hi, thanks so much. I just want to ask whether briquilimab is going to be an attractive, c-Kit targeting is going to be attractive for asthma in terms of safety. Don't you think that there's going to be obviously the c-Kit-targeted toxicities and also more of a risk for anaphylaxis in this population, especially when you think back on the fact that Xolair's black box warning for anaphylaxis was kind of more of an issue with asthma patients than in urticaria patients? Thank you so much.
Good morning, Jeanna. Thank you for the question. Dr. Wendy Pang has joined us on the call here, and I think it'd be great for her, as a treating physician, to address some of those safety questions. Wendy?
Yeah, thanks, Ron. So, I think the issue that you're bringing up is an important one. However, I think the key here is that for briquilimab, it's an aglycosylated antibody, and we have demonstrated that this aglycosylation actually minimizes the potential for hypersensitivity reactions because it actually doesn't recruit immune cells to the mast cell. Whereas if you think about other mast cell-targeting antibodies that have wild-type Fcs, they will recruit immune cells to mast cells, and these immune cells, because they contribute to an inflammatory environment, can trigger degranulation of that mast cell. And with regards to the differences between an asthma population and a non-asthmatic population in terms of hypersensitivity reactions, it really depends on again that hypersensitive milieu.
And we think that briquilimab, you know, while we can't fully eliminate any potential hypersensitivity reaction, because it's really an antibody class effect, by aglycosylation and eliminating the potential for that Fc receptor to recruit any immune cells or immune mediators, through aglycosylation, we think that we can potentially minimize the unwanted effects.
Thank you, Wendy.
Thank you, sir. Thank you.
Thank you for the questions, Jeanna. Our next question comes from Gavin Clark-Gartner at Evercore. Please go ahead, Gavin.
Hey, thanks for putting on this, really great event. So I'm just wondering, what's the impact of corticosteroids on mast cell counts, and how may you, control or account for this in subsequent trials?
Good morning, Gavin. Wendy?
Yeah, thanks, Ron. So steroids, they have an impact on a number of different immune cell types. It's not as clear in terms of their direct impact on mast cells, but because steroids have a profound impact on neutrophil counts and numbers and where they go, as well as T-cell function, and because all of these cells play a role in what is a dynamic immune process in a disease like asthma, we think that yes, certainly steroids will have an effect, but in subsequent and later trials, I think, the potential population for using that we may target that includes, you know, the severe asthmatic population. They actually tend to be very steroid unresponsive or poorly responsive.
We think that by targeting the mast cells, which are actually not directly targeted by the steroids, we have the potential to really break an important link in that complex immune web, if you will, that makes up asthma. And I think that's the potential for briquilimab in a disease such as asthma.
That's helpful. Thanks, Wendy. And this may be too early to speculate on this, but is it possible that c-Kit inhibition and mast cells in general may have greater roles in different part of the diseases? So in other words, is it possible there could be a larger benefit on exacerbations in clinical trials and maybe a slightly smaller benefit on FEV1, or we have to just see some data to find out?
I think we'll need to see some data to find out, but because I would say that we know that mast cells are an intricate player in this inflammatory milieu, and because briquilimab can potently impact mast cell numbers, there's the potential to see an impact across all of those measures that you just mentioned.
Awesome. Thanks again for putting on the event.
Thank you, Gavin.
Thanks for the questions, Gavin. So our next question comes from Greg Renza at RBC. Please go ahead, Greg.
Great. Thank you. Good morning, Ron and team. Thanks for putting the event on, and thanks for taking my questions. Ron, maybe two questions for me for the team. Just relative to briquilimab's positioning, what does briquilimab need to demonstrate to be competitive with other biologics in severe asthma? Just curious on you and your team's view on that. And then secondly, just in terms of urgency and prioritization, what would you view as the most optimal timeline to get to the proof of concept and eventually just to register briquilimab in severe asthma? Thanks so much.
Good morning, Greg. I'll start with the second question. So this is clearly a priority for us. We believe that there's strong clinical and preclinical rationale for this disease, and it's why we intend to initiate this study before the end of the year and hopefully conclude it before the end of allergy season through the course of the winter. I think you know, if we're successful there, then moving forward into a true phase II dose-finding study, either the latter part of next year or early 2026, could then put us on a cadence that maybe brings asthma in you know, 12 or so months behind a potential timeline for an urticaria approval.
We're putting together an aggressive timeline here, but we think that the opportunity certainly warrants that. Again, if we follow the biology here, as we have in the urticarias, we believe there's a high probability and risk reward to move forward in that fashion. I think as it relates to the positioning here, you know, it always starts with safety. The current data we've generated to date certainly looks as if we can safely deplete mast cells and having that depletion be durable.
What we know about the mast cell, again, is that we can safely live without skin mast cells, and it will be one of the key learnings from this study, is to understand what level of depletion in the lung and what does that tissue type look like for the return of the mast cells. But everything certainly looks like this briquilimab could be safe in this setting. And then, ultimately, you know, if we're able to, similar to what we're doing in CSU, be able to provide patients with an opportunity that maybe is an administration of only once a quarter or potentially longer, that could be a significant benefit in this setting.
And ultimately, I think, as Wendy was speaking to, and I think you heard Dr. Boyce as well, is that you know, thinking about the three phases of asthma, you know, with the last phase being the remodeling, is that if, in fact, we're able to really interrupt this disease and remodel, then this could be a significant opportunity, and a meaningful choice for patients in the future.
That's great. Thanks for all the color.
Thank you, Greg.
Thanks for the questions, Greg. Our next question comes from Matthew Phipps at William Blair. Please go ahead, Matthew.
Morning. Thanks for putting this on and taking my questions. Yeah, I was wondering if there's any evidence from either the imatinib or masitinib trials that looked at maybe time to rebound of tryptase levels after stopping treatment, if that could kind of help inform the frequency of briquilimab infusion you would need in asthma?
Wendy?
Yeah. Thanks for the question. So for tyrosine kinase inhibitor, such as imatinib or masitinib, they while they can inhibit c-Kit, they don't inhibit, at least to the levels that you can dose patients with, to the limit, or to the extent that we need to actually induce mast cell apoptosis. So mast cells only undergo apoptosis when c-Kit signaling is completely inhibited and blocked. And that's what briquilimab can do, because it's very potent, and it binds with greater affinity and avidity to c-Kit than its normal ligand stem cell factor. But c-Kit inhibitors can't do that. So when we look at the masitinib and the imatinib studies, we don't think, and the evidence suggests, that we are not driving significant mast cell apoptosis in that case.
So if we're not driving mast cell apoptosis, it's hard to assess mast cell repopulation in using c-Kit tyrosine kinase inhibitors in the data that we have to date. But I think we can look at briquilimab and the early preclinical studies and our healthy volunteer studies, and we think that it does take, as Ron mentioned, on the order of weeks to months for mast cells to start repopulating in various tissues. I think the other thing important here to note is that because an imatinib or a masitinib does not actually induce significant mast cell apoptosis, they would need to be chronically administered, and these tyrosine kinase inhibitors clearly come with other off-target toxicities.
And they are really off target here, because they're not targeting cells with c-Kit expression, but they can influence liver function and other organ function. So I think we have to be careful with long-term tyrosine kinase inhibitor use, because it can bring on potential adverse effects that a specific antibody, such as briquilimab, we don't expect that it would happen with briquilimab.
Got it. Thanks, Wendy. That makes sense. One quick follow-up. Did you guys say at what kind of time point you would do the asthma challenge? Just wondering, how many doses of briquilimab would be given prior to that? I guess, you know, do you think it'll have as rapid an effect as it does in something like CSU, or will it need a little bit more time on treatment before seeing benefit? Thanks.
Wendy, do you care to answer that?
Yes, sure. So, we think that mast cell depletion in the lungs, from what we've seen in both our mouse models as well as our non-human primate models, is very robust and we believe actually rather quite rapid. And so we anticipate that we would be able to rechallenge basically these individuals with the antigens that can induce their asthmatic response relatively early, you know, on the order of weeks. And we do think, based on the data available, that a single dose of briquilimab will be, you know, will be sufficient to see a change in the asthmatic response to allergens. So we intend to challenge the patients in our phase one on the order of weeks.
The exact study design, we are still finalizing, and we're in discussions with the regulators, so I don't want to comment on the exact final design until we've had a little bit more progress in that area.
Very helpful. Thanks, Wendy. Thanks, everybody.
Thank you, Matt.
Thanks for the questions, Matt. Our next question comes from Pete Stavropoulos at Cantor Fitzgerald. Please go ahead, Pete.
Yeah. Hi, Wendy and team. Thanks for hosting this call. Is there anything from the healthy volunteer data that you collected or the data you will collect from the CSU study that will help inform them, the dosing and timing for the challenge in the asthma proof of concept study? And how are you thinking about leveraging the data from the imatinib studies?
Wendy, would you like to address that?
Yeah, sure. So, the data from the healthy volunteers, we have basically some markers of skin mast cell depletion. And we have, based on our preclinical models in mouse and in non-human primates, a general sense of the relationship between mast cell depletion in the lungs and the skin, in both of those tissues. And part of the reasons why we've elected to go into these areas is that the depletion is profound and rapid. And so we think that the mast cells in these tissues are very responsive in terms of going down the apoptotic route after briquilimab exposure.
And so, we think that this is going to, you know, this has already helped us really go and pick the direction that we want to take the briquilimab franchise. With regards to the urticaria studies, we are doing, you know, as most of you know, a dose escalation trial in the BEACON study, for example. And we will have data already by the time we start the asthma trial into mast cell depletion in the skin, because those patients do receive skin biopsies, and we can make, again, you know, those similar calculations and comparisons and make a very informed decision by the time we dose our asthma patients.
Okay. In the New England Journal of Medicine paper, you know, that was published for imatinib, there was a total of about 27 secondary outcome measures that were pre-specified in the protocol. And there were various inflammatory measures they looked at between baseline and after six months of dosing. You know, are there any other measures that they published or released that were, you know, directionally positive, that helps build confidence that c-Kit and the mast cells are the right target? And can you speculate with depletion of mast cells, will it be a larger signal?
Yeah. So the imatinib study, for example, they were looking specifically at severe refractory asthma patients. And so the measures, the outcome measures for that population are going to be different than the population we are starting out in, in our earliest phase, which are, you know, those patients with mild allergic asthma, just as a starting point. But I think when we do go into the severe asthma space, based on data from this phase one trial, that I think the key measures really are in this space at least, they are the withdrawal of steroids and other maintenance medications from these patients' medication lists.
And these other outcome measures, I think they do reflect improved quality of life and improved just overall well-being of these patients. And so certainly the list of secondary outcomes that was done in the KIA or the imatinib study, we will be evaluating as potential outcome measures for a future briquilimab study. If as you know, your question is, are there other secondary measures? There probably are. That's going to take you know, a weighing of the pros and the cons of including each particular measure in a larger study. So we don't have an exact prescription for that, if you will.
Okay. Thank you for taking my questions.
Thanks, Pete.
All right. Thanks, Pete. Our final question comes from Emily Bodnar at H.C. Wainwright. Please go ahead, Emily.
Hi, good morning. Thanks for taking the questions. I'm curious, based on your, your discussion earlier, it sounds like you think there could be potential differentiation in Type 2 low patients. So are you kind of planning to focus on, on that population, or do you truly think this could be broadly effective across different types of asthma patients? And, which endpoints do you think are, are most relevant for, for the Type 2 low patients that you might be looking at? Thank you.
Certainly. Well, I'll take the first part of that question and then ask Wendy to respond to the second. We think ultimately, as the mast cell is a major contributor to this disease, and that it really doesn't matter, you know, the endotype. The mast cell is there across the endotypes, that if we're able to safely deplete the mast cell, then it's more about that than the endotype. So we do think that this could have broad applicability. Wendy, anything you'd like to say about the second part to the question?
Yeah. So I think it's important to realize that mast cells interplay in terms of their cytokine and chemokine signaling with both TH1 and TH2 immune pathways. So mast cells play a role. They're a link in both of those inflammatory responses. So by targeting mast cell depletion with briquilimab, we think there is potential to impact these patients, whether they are Type 2 low or not. In terms of measurements, it's, I think, really the gold standard in the asthma space right now is whether you can take them off their existing maintenance therapies, which can be very difficult to manage.
And oftentimes, for these particularly severe asthma patients, they're very poor at controlling their asthma symptoms. So the gold standard, I think, applies across the asthma endotypes, which is if you can withdraw their existing maintenance medications, especially the more difficult or more side effect-prone meds.
Great. Thank you.
Thank you, Emily.
Yeah, thanks for the questions, Emily. So this concludes our Q&A session for today. I'll now turn it back over to Ron for closing remarks.
Great. Thank you all for joining us here this morning. I hope you share the enthusiasm and excitement that we have for briquilimab and for the opportunity in asthma. We think based on the preclinical data, both generating and generated in academic labs as well as our own and with our proprietary Jasper mouse that support that significant clinical data here validating the clinical relevance of drugging c-Kit in asthma, along with the unmet medical need, make this a clear choice for us for our next indication to develop briquilimab, and further as an example of the portfolio opportunity that is briquilimab.
We look forward to the balance of this year, bringing forward data from the BEACON study, the SPOTLIGHT study, and then initiating our first clinical trial in asthma. So thank you again for your time, and look forward to updating you on the company's progress throughout the course of this year.