Hey. Welcome, everyone. We're going to get started here. I'm Gavin Clark-Gartner, one of the biotech analysts here at Evercore ISI, and I'm really happy to be joined with Ron Martell, who is the CEO of Jasper Therapeutics. Thanks for joining us, Ron.
Gavin, thank you very much. And on behalf of all of my colleagues at Jasper, we really appreciate all the support from Evercore and from all the work you do.
Absolutely. All right, so let's dive right into it since we only have 20 minutes. Good place to start. Why don't you just give us an overview of Jasper Therapeutics and where things stand today?
Sure, so Jasper Therapeutics, we're a clinical stage biotech company. Our lead program is a monoclonal antibody targeting c-Kit, specifically as a therapeutic targeting c-Kit on mast cells. We have three ongoing clinical trials, one in inducible urticaria where we announced some top-line data a few weeks ago, another one in asthma where we announced yesterday we've dosed our first patient, and the third clinical trial is in chronic spontaneous urticaria, also known as the BEACON study that we've guided. We will have the top-line data from that clinical trial the week of January 6th.
Awesome. All right, so let's start off by focusing on urticaria since that'll be the nearest term data update. And I wanted to specifically spend a good chunk of time laying out what you've kind of called the optimal biologic dosing profile, also kind of called Therapeutic Window, and specifically how that enables differentiation versus other c-Kit antibodies and barzolvolimab. So maybe that's just a good place to start. Why do you think your dosing paradigm is ideal? What attributes of briquilimab enable that?
Sure. Well, we think that using an optimum biologic dose in these diseases, specifically targeting mast cells, has significant therapeutic advantages. We know, the field knows that c-Kit is the primary survival pathway for mast cells. If you dose to a certain concentration or Cmax that will shut down the receptor, you shut down all internal phosphorylation, you shut down FOXO3a. FOXO3a is responsible for regulating Bim. Bim initiates apoptosis. So if you follow that biology and you know that you can then deplete mast cells, you really approach this disease based on the biology of the mast cell. What's the ideal dose to deplete those mast cells? Then we also know that it takes a while for mast cells to repopulate the skin. So what's the timing of that next dose and how much drug would you give based on the return kinetics for the mast cells?
And so we think that this will not only provide us with an opportunity to have maybe the optimal dose and strategy that's convenient for patients to drive efficacy, but potentially could be a safer regimen as well.
Yeah, that makes sense. And just to probe on one of the points, you mentioned it's getting to a certain Cmax concentration to trigger depletion. It's probably some degree of maintaining that concentration. And we're not exactly sure how long that is. Do we have any hypotheses for what that length could be, roughly what that concentration is for briquilimab too?
You know, that's what we're really going to learn in the BEACON study. So what we know is that mast cells, at least in a dish, begin apoptosing within hours. And if you look at the data from barzo when they did skin biopsies, you saw within the first couple of days, you saw mast cells started to be depleted from the skin. Now, when you take that data and that thought and you look at our most recent study, the SPOTLIGHT study, within a week, the vast majority of the patients, almost 100% of the patients who were going to respond, which we had 93% of the patients respond to the drug, had that response within a week.
It tells you that with briquilimab, at least we can hit that Cmax quickly, not quite like a Tmax, but our Cmax almost looks like the Tmax. And then you start that apoptosis and that activity happens really fast, and then you see the clinical efficacy happen rapidly.
Yeah. And thinking about the different safety profile and the adverse events where you may differentiate, maybe just lay out what those are.
Sure. So we've been discussing c-Kit on the surface of mast cells. c-Kit is also present on four other cell types in the body. It's present on stem cells, arguably the most important cell in the body. We'll come back to that. It's present on taste buds, on melanocytes, and the progenitor of the spermatogonia. So it plays a different role on each one of those cell types, but an important role and important to understand how when you're blocking c-Kit on a mast cell, how you might see those then on-target effects.
But equally important, going back to your very first question about optimum biologic dosing, that if we are depleting mast cells, but yet you continue to dose with the same level of drug that you had on board, and if you have depleted the mast cells or substantially depleted the mast cells in the skin, then that leaves free antibody to hit these other c-Kit presenting cells. And we think that that then could translate into a safety difference between our drug and barzo.
Yeah, got it. And for the different events, I mean, there's neutropenia, there's hair color changes, maybe some skin color changes with longer-term treatment, and maybe partially depending on dosing, right? So this is just mechanistically what we've seen. For those different adverse events, do you believe any are most important to differentiate on?
I certainly think from the hematology side, and you mentioned neutropenia. So again, c-Kit is present on stem cells. Importantly to know that stem cells have redundant survival pathways. So just blocking c-Kit on the surface of a stem cell will not kill that stem cell. It makes them go a little quiescent for a little while. When we've looked in the bone marrow of patients, we see that the reticulocytes nadir between day eight and day 12, but by day 28, they come back to baseline. So really important to see if, again, with our dose and strategy, if we're able to provide these patients with an opportunity to have their bone marrow recover off of what that nadir might be off of that first dose.
And again, that could be a significant differentiator between us and barzo because they're dosing more to an AUC or an MEC. And so they're constantly having drug on board. And from the data that they've released earlier, it suggests that they see that first dose effect. We would expect we do as well. But then over their 52-week period, they maintain that suppression of the neutrophils. And so we're seeing if we can avoid that constant suppression of the neutrophils.
Yeah, got it. And a question that we get frequently is, you know, Celldex has shown with barzolvolimab that serum tryptase does seem to correlate pretty closely with clinical efficacy. Why do you think this is maybe not necessarily the best biomarker? I guess what room on the table does this biomarker leave?
Sure. So we know that serum tryptase is an important biomarker. It's produced by mast cells. 99% of the tryptase in the body comes from mast cells. A little bit comes from basophils. So it's a biologic signal of an active mast cell. So if you're seeing the tryptase go down, you're seeing an inhibition or a suppression and maybe depletion of mast cells. So it does correlate with the clinical efficacy. However, on an individual patient basis, the predictability is just not there. Why do I say that? As an example, the data from our SPOTLIGHT study that I was discussing earlier, we had one patient in that study that had a complete response, but only saw a 50% reduction in tryptase. We had another patient who had a complete response. Their tryptase nadired, then it came back 70% off of that nadir, and they maintained their complete response.
So while it definitely correlates to, it's not predictive of efficacy.
Yeah, that makes sense. All right, so let's transition to think about what an optimal dosing interval could look like. I guess one of the questions embedded in this is how long of a drug-free or a low-concentration drug period do you really need for some of this differentiation on the safety side to come through? You know, is it one, two, four weeks? Do we have any idea?
I think any interval is better than none. The question is, what is that optimal interval based on the return kinetics of the mast cell? That's really unclear at this time. There's some early data that suggested with barzo, with a single dose of 3 mg IV, that they saw complete depletion of the mast cells, and it took the mast cells about 18 weeks to come back. We think that that's not likely in your average patient, again, with the kinetics of the tryptase as well. We think with our half-life, our half-life is only about nine days. If you think three and a half half-lives for clearance of the antibody, any interval longer than about a month for dosing would provide anywhere from four weeks or more for patients to have a drug-free interval, which could be meaningful.
Again, if we, as an example, looking at the stem cells and where we saw the bone marrow rebound by day 28 or day 29, that means you could be potentially giving patients a month or maybe even longer, depending on our dosing interval, with a healthy marrow without any insult from blocking of c-Kit. And I think that this also could translate into a potential benefit also to your earlier question regarding the potential graying or hypopigmentation.
Yeah, got it. And if we were to just say in a silo, you know, you're testing eight weeks and 12 weeks as your longer intervals in the ongoing CSU study, how important in a silo is the 12-week dosing interval commercially, or is it really more about the drug-free period? I guess to ask a little differently, you know, if you have eight weeks where it looks like some of the safety differentiation is coming through, maybe it's even towards the 10 weeks, but you know, by the time you hit 12 weeks getting out that far, you know, you do see more of a disease rebound. You know, how do you think about that result as long as you're getting some of the off-drug period?
Yeah, so first and foremost is establishing that we have efficacy that is comparable to Celldex. If we establish that, then we have a drug and we're only 12-ish months behind them. We're the definition of a fast follower. Secondly, if we can differentiate on safety and if we can illustrate, again, it's a modest sample size in the beacon study, but if we can illustrate that there's trends towards a safety difference here, that's a really big win. And convenience is then really nice to have. If we're on an eight-week schedule, asking patients to come in every eight weeks to their derm for a 2 ml Sub-Q, potentially ultimately delivered in a pen that they could take at home and forget about your disease. I don't know how much difference there is between, there definitely is a difference between every four weeks and every eight weeks.
Eight weeks to 12 is nice, but you know, that's not a deal breaker.
Yeah, well said. All right, so thinking forward to January 6th that week, as you do show the initial CSU data, can we just lay out what's the trial design, what doses will be included there, what kind of follow-up will you have when you have that data, and then also just lay out the different measures, you know, will we have the serum tryptase, the UAS7 curves, et cetera, just kind of lay out that update?
Sure. So we designed the BEACON study to address all of your previous questions, really the optimal biologic dosing. So we're looking at a number of different dose levels, as well as a number of different dose intervals and dose levels based on those dose intervals. So we're starting; we have cohorts that start at 10 mg, then 40 mg, then 80, 120, and we're testing Q8 and Q12, then 180, Q8 and Q12, and then 240. The 240 mg dose level, we initially designed the study thinking about a loading dose or an induction dose.
So, is there the rationale to hit the mast cells even harder upfront with a loading dose, drive as deep a depletion, does that change the mast cell return kinetics and potentially even provide an opportunity for a longer dose interval after that first dose and maybe even then a reduced dose after that because now all you're really doing is maintaining that depletion that you've already achieved with the larger dose? A number of different cohorts that we'll be presenting data on the week of January 6th. What we'll have is we will have primary efficacy is UAS7 and UCT at 12 weeks. We will have serum tryptase on all patients over the course of that efficacy period. So we'll have a lot more data to share as it relates to tryptase.
And then I think importantly from a safety standpoint is we will have comprehensive longitudinal safety data on all patients in the BEACON study for their entire time on study. So not just safety for the 12-week efficacy period. So you'll get a good look at what it means to take 120 mg every eight weeks and have six months or potentially more of safety data.
All right, great, and let's be a little more specific or quantitative on kind of the expectations for the trial, so thinking about the efficacy bar on UAS7 to roughly match barzo, are you guys laying out like a reasonable range you might expect?
I haven't really laid out a reasonable range. I think I use the word comparable. Again, small sample size. And so, you know, one could imagine a scenario where we're significantly better than them, but again, small sample size or, you know, if we're a few points less than them, you know, we need to make certain we're within that range of where they are.
Yeah, yeah, that's very fair. And then turning to the safety side of things, the ability to discern some of, it'll be early, right? But the ability to discern some of that early differentiation, like if you take hair color changes as one example, because we're unlikely to see hypopigmentation in a shorter study, but you just kind of take the hair color changes. There's been variability in the different barzo studies. Is there any type of range you guys are looking at and, you know, what would be early potentially best in class data on that measure?
Yeah, to your point, there's been variability in the studies reported to date, and that possibly has something to do with investigator and patient bias here. As a reminder, you know, the median age for patients in these trials is 40+ , so you know, there's naturally some graying going on and how do you differentiate the graying that's taking place via the study or not. I think, and I would agree with you that, you know, probably within the safety time window that we're looking at here, that likely the opportunity to see the hypopigmentation probably won't be observed.
Yeah, that makes sense. I'll quickly ask about potential for any hypersensitivity reactions or, you know, anaphylaxis, however exactly you want to define that in whatever you're seeing or not seeing in the study.
Yeah, well, to be clear, we remain blinded to the study. The only data that's been observed by anyone in the company is the safety officer who has seen the blinded safety data and reviewed that along with the IDMC. What I can say is that we've had no discontinuations in the study, no drug holidays in the study, and no reported anaphylaxis in the study.
All right, great. And my last one, as you'll be sharing this data, should we expect any data from the CIndU study, particularly at the 180 dose?
I think it's based on the timing of initiating that cohort. It's premature. Once those data mature sometime in the first half, we'll bring those forward and likely present them at a scientific meeting.
Yeah, that makes sense. And that puts us right at time. We didn't even have time to talk about asthma, but I suspect as we go past the CSU data into 2025, we'll be talking about that a lot more. So.