Good afternoon, everyone. Thank you for joining us today at the H.C. Wainwright Global Investment Conference. My name is Emily Bodnar, and I'm an Equity Research Analyst at H.C. Wainwright. I'm pleased to introduce Ronald Martell, who's the Chief Executive Officer of Jasper Therapeutics. We'll be doing a fireside chat this afternoon, so maybe to start for those who are newer to the story, could you provide us with a brief overview of Jasper, some of your pipeline programs and recent milestones?
Sure, happy to. First, Emily, on behalf of all of my colleagues at Jasper, we thank you and H.C. Wainwright for this opportunity this afternoon, and I probably should remind everybody also that certain comments I may make today may constitute forward-looking statements. Yeah, so Jasper Therapeutics, we have our lead program is a monoclonal antibody called briquilimab. We call it bric for short. And we are focusing on utilizing that antibody to target c-kit on mast cells, and we currently have two ongoing clinical trials, one in CSU, or chronic spontaneous urticaria, and another one in inducible urticaria, and we announced this morning that Canada, Health Canada has cleared our CTA or our IND to begin our asthma study.
In Q4, we have a corporate goal of enrolling the first patient into that asthma study.
Great. As you mentioned, briquilimab targets c-Kit. So how does c-Kit play a role in urticaria, and specifically in mast cells?
Sure. So mast cells, as everyone knows, they're one of our important immune cells. And they're primarily in the skin, and in epithelial tissue, so in the skin, the lung, the gut. They're a fairly primitive cell. They were originally designed by the body to defend us against venom and parasites. So as an example, the appendix is loaded with mast cells. But in a modern world, they don't play that much of a role in our bodies anymore from an immune standpoint. However, they're present, and when they're triggered in diseases like urticaria, they create these significant rashes, or in asthma, they're the conductor in the orchestra that initiates the entire release cascade in asthma.
So mast cells, their primary survival pathway, is this receptor called c-Kit. And what's really important about mast cells are that it's the c-Kit is the primary survival pathway, and if you block the natural ligand, stem cell factor, or SCF, from binding to c-Kit, you will shut down all downstream signaling. You will shut down phosphorylation, and if you block with a high enough concentration on the surface of the cell to block enough of the c-Kit receptors, that will initiate. The cells will undergo an organized cell death or apoptosis, and that's the primary mechanism here. So it's really important to also know that in diseases like urticaria, the mast cell actually isn't diseased.
It's the same mast cell that you or I or someone who does not have urticaria have in their skin, but there's something else in the immune system that's triggering it. But this is one of those unique opportunities in medicine where you know what that perpetrating cell is, and now we have an opportunity to actually deplete that perpetrating cell with what currently looks like a very acceptable safety profile.
So c-Kit has gained a lot of clinical validation as a target from Celldex's barzolvolimab. So how does briquilimab differ from barzolvolimab in construct, and does it have potential to be differentiated?
Certainly. So, both antibodies, as you describe, are antibodies to c-Kit. They're both humanized IgG1 aglycosylated antibodies. The similarities stop there, though. First, with the aglycosylation. So it's really important, and Novartis taught the field years ago that you really need to nullify that Fc. The last thing you wanna do if you're treating mast cell diseases is bind complement or activate ADCC or CDC around a mast cell. So you need to nullify the Fc. So, our antibody was originally designed by Amgen, and they utilized a technology that they and others in the field have routinely used for nullifying the Fc. So at N297, there's a single mutation or change that was made in asparagine to a glutamine.
On the other hand, Celldex and their antibody barzolvolimab have made six structural changes to their antibody, a couple to nullify the Fc and a couple to lengthen the half-life. Why is that important? It's known in the antibody field, the more structural changes you make to an antibody, the more opportunity the body has to see it as foreign. And what's the outcome of that? The body produces ADAs or anti-drug antibodies if they view it as foreign. And at least early data indicate that there's a significant difference there. To date, with our sub-Q formulation, we've only seen about 14% ADAs. To date, those ADAs have not affected the PK or the PD of briquilimab.
On the other hand, Barzo or barzolvolimab, with their IV formulation, has observed about 51% ADAs, and they haven't disclosed yet what their ADA rate is with sub- Q, but I wouldn't be surprised if it is slightly higher than what the IV formulation is. It's known again in the field, when you use it as sub- Q, the antibody gets into all 5 compartments, and you generally have more ADAs. So we'll see how that plays out, clinically. There's also a difference in the half-life, as I described. Our half-life is only about 9 days. Theirs is 21 or 22 days. In oncology, you often want to have a longer half-life.
However, in treating mast cells, we think it's an advantage to have a shorter half-life because, again, if you're initiating that apoptosis, and those mast cells are dead and dying and all leave the skin within a couple of weeks, then you really don't want the drug around because c-Kit is present on other, cell types in the body, so it may confer a safety advantage. The last difference, structurally, our antibody, briquilimab, is designed to bind to the epitope, the binding pocket of the natural ligand SCF. Barzo, on the other hand, is an anti-dimerization antibody. It binds further down the stalk, more at, like, four or five. So in theory, there could be a potency difference here as well, because SCF could still bind in the presence of Barzo, where it can't bind.
We bind with a higher affinity and avidity than the natural ligand.
You presented phase I data in healthy volunteers, and you've shown mast cell depletion in that study. So how has the different doses that you looked at kind of informed your phase II development that's ongoing now?
Sure. So, there was a study in healthy volunteers, as you describe, and there were four dose levels in that study, 42 milligrams, 84, 158 and 280 . And what we observed was at the 42 milligram level, there was only one subject that had any mast cell depletion, a lighter weight patient. So maybe that dose level reached that threshold of concentration to initiate the apoptosis.
When we went over to the 84-milligram dose level, we depleted about 60% of the mast cells in that population, and we saw a nice corresponding dose curve then as the dose levels went up, and so that informed us for the BEACON study, our study that we're running in CSU, that our initial dose to find efficacy starts at around 80 milligrams, and then we escalate the dose from there to 120 to 180 and 240.
Great. So you recently announced an addition of a 180 mg Q8 weekly dose in the phase II study. So what drove the decision to add that arm, and how are you kind of thinking about potential for various dosing regimens like Q8 weekly versus Q12 weekly?
Sure. So yes, when we recently on our earnings, when we announced the data will be coming in Q4 now, and for the entire study, with the caveat that this new cohort that we just added, we'll see about enrollment on that. But we added that cohort, quite frankly, because we could. We could from the standpoint that it was important when we designed this study with the FDA and EMA, that it would be easy for us to add cohorts as we move forward. This field is changing rapidly, and quite frankly, we're learning a lot from Celldex. So we wanted the opportunity to be able to add cohorts easily. And then the other is that we could because enrollment has gone so well.
You know, in the late spring and early summer, enrollment really picked up, and so it enabled us to add this extra cohort without having any delay to the overall timing of the study. And never has a drug developer ever said, "You know, I've generated too much data." And so it gave us an opportunity to look at yet another dose level and interval that could inform us both in CSU and CIndU, but as well as other different indications that, like our asthma, and we announced this morning that we're moving forward in the asthma study with a hundred and... in a moment we may have the new cohort, the 180 Q8-week in that timeframe as well. That will be an initial data readout. It'll be more of a snapshot, if you will.
So we will absolutely have the primary endpoint of UAS7 at 12 weeks on all subjects. We'll have their UCT scores, same thing at 12 weeks. We'll have the tryptase data, and we'll have the safety data on all of those patients in the study. And we'll see at that time, you know, just how much data cleanup needs to be to how much more data we can present. And then we would look to potentially a meeting like QuadAI in February to provide the full study report. From an outcome standpoint, what we would anticipate is that at least one of these dose levels will show data that's comparable to Celldex. And so when I say comparable, I'm really talking about a 12-week UAS7 score.
And so if we have data that look comparable to Celldex, that means we have a drug, and we're off and running, and it only puts us twelve-ish months behind them. We're sort of the definition of a fast follower. I think where we go from there is sort of the baseline is, if we're able to dose at intervals that are longer than Celldex, that may be more convenient for patients. And then lastly is, if the combination of those dose intervals and with the shorter half-life give the patients a longer drug-free interval, then that could potentially translate into a safety advantage as well.
Yeah, I think you bring up a good point, given there's really not much out there for CSU aside from Xolair. So how do you kind of think about the market opportunity, potentially for multiple c-Kit inhibitors? And also, barzolvolimab is now entering phase III, so do you kind of view that program as the benchmark for you going forward?
Certainly we view barzo as the benchmark. First, I think it's really great for CSU patients that this is a patient population that for decades have really had nothing but antihistamines at four times the daily level. I can't imagine living life like that. There are a number of posters this last year at AAAA I talking about how depressed patients are and how bad they feel because they're taking such high levels of antihistamines. So great for patients. I also think it's great for the overall market. A good analog here is the psoriasis market. Eight or 10 years ago, there were sort of these same questions: just how big is that market? You know, can it handle multiple competitors? Will derms like biologics?
Now we know there's more than eight drugs that do more than $2 billion a year. I think that's a good analog for this market. I think the last thing I'll say there, and it's a bit overly reductive, but. You can really divide the drug development world into those drugs that deplete mast cells and those that inhibit mast cells. Currently, the only drugs that have demonstrated they can deplete mast cells are briquilimab and Barzo. All of the other drugs inhibit the mast cell, and all those drugs are largely oral with the exception of omalizumab.
And the issue with that approach is that you need to maintain 24/7, 365 inhibition, or as soon as, you know, a patient is not compliant with taking their drug to maintain that inhibition, then the symptoms are going to come right back, so it'll be really interesting to watch this landscape over the next few years.
Yeah. Maybe moving on to chronic inducible urticaria, where you also have a phase Ib/II study. How does the design of that study relate to the barzolvolimab phase I study that we've seen data for, and how do you kind of think about the bar, given we've now seen phase I and phase II data recently?
Yes. So our design of our so-called SPOTLIGHT study in inducible urticaria is designed pretty much exactly the way that Celldex designed their initial phase 1 study, a single administration of briquilimab. The patients come in, and we're really enrolling two types of inducible urticarias, symptomatic dermographism and cold urticaria. Those patients will come in, they'll receive what's called provocation tests, so either a scratch test or a cold test to induce their urticaria. Then they'll receive a single dose of briquilimab. We'll follow them for 12 weeks, and then they'll receive that same test and see how they did versus baseline. So, that study will also read out here in Q4.
Yeah. I think, with the phase I study for Barzo, I think we saw almost, like, a 95% complete response rate, whereas in phase II, the numbers looked quite a bit lower than that. So how do we- how do you kind of think about, you know, like, the true efficacy and where you kind of want to end up?
Yeah. That's a great question, and unfortunately, I think that there's been some confusion around those two studies. And I don't think it was explained really well that in their phase I study, that 90%+ that you refer to, that was because in their phase I study, they permitted patients at any time in the 12 weeks to have that response, and they called it a complete response, as opposed to in their phase II study, it was only at 12 weeks. So you saw a bit of a drop-off in that because it was only at the 12-week timeframe.
Okay. Yeah, that makes sense. And as you mentioned, you recently received the CTA approval for the asthma study, so maybe just discuss how you identified asthma as the next indication, and that's also an indication where Barzo is not being evaluated. So just, I guess, discuss the opportunity and potential for targeting c-Kit in asthma.
Sure. So we've looked at more than thirty diseases. We think that, diseases that are mast cell mediated or mast cell driven, are greenfield for us and really present a lot of opportunity. We obviously went into CSU and CIndU because of Barzo's proof of concept there. They, they've taught us in the field, that, you know, these drugs work there, so it was a logical place for us to go. For our next indication, we chose asthma, and we really followed the biology here, as well as importantly, what really pushed us over the line is additional clinical development. So, Amgen originally, as I stated before, looked at briquilimab for. They were developing briquilimab, and they were developing it for IPF.
So they did a significant amount of preclinical work, and including a couple of NHP studies, where they looked directly in the lung of these NHPs, and were looking at mast cells and demonstrating that briquilimab could deplete the mast cells in the lung. In addition to that, we have the Jasper mouse, and with the Jasper mouse, we were able to conduct an asthma challenge study there, as well, and showing that we could improve the airway in the rodents. But really, the important piece was, there's been two clinical studies, one with imatinib and one with another small molecule called masitinib, and in these two studies, they demonstrated in human clinical trials, the fact that if you're blocking c-Kit, you can have this positive impact on the airways.
The one was, the imatinib study was published in the NEJM, and the masitinib trial went all the way to phase three and showed a 33% reduction in exacerbation. So, the combination of the preclinical data, and more importantly, the clinical data here of the benefit of blocking c-Kit, really told us that that was a great indication for us to go into.
How, how does briquilimab kind of differ from these c-Kit inhibitors that kind of have a different mechanism of tyrosine kinase inhibitors? And you know, how, how are you kind of expecting to potentially see differentiated efficacy versus what we saw with those initial programs?
With the small molecule, c-Kit-
Yeah
Inhibitors? Yeah, I think the challenge with the small molecules is that their specificity. So unlike an antibody, that's the wonderful thing about an antibody, is there's an E to T of one, right? You know that it's going to target that epitope, and you can design it, so it will only bind to that epitope. On the other hand, c-Kit small molecules have the opportunity to get into a lot of other cells in the body, and the challenge through historically, through development, is: how do you create something that's targeted enough, and then how do you get it to concentration safe enough that you can inhibit the mast cell?
I haven't seen anything to date that would suggest that they can get to concentrations that can deplete the mast cell, but how can you get to concentrations high enough to inhibit the mast cell? And then it goes to what we were talking about just a moment ago, is really patient compliance, because you have to. That mast cell is still there, so as soon as you don't have enough concentration to inhibit that mast cell, the patient's symptoms will come back immediately.
How are you thinking about potential next steps in asthma beyond the asthma challenge study that you're planning to initiate soon, and what is kind of the development landscape look like there?
If we're successful in this study, and this study will teach us a lot, if we're successful here, then we would anticipate running a much larger phase two real dose-finding study, starting probably Q4 of next year. And I think the real interesting thing is here. Well, a couple of things. One is, as I stated before, the mast cell is sort of the conductor in the orchestra. It's well understood that the mast cell initiates the release phase in asthma. So everything from prostaglandins to histamines to R2, it releases all of these things that really initiate and create the asthma response that a patient gets. Interestingly, the mast cell is also very much involved in the recruitment phase, so things like eosinophils, Th2.
It'll be really interesting to see in this study if what impact do we have, as an example, on eosinophils. Because, as you probably know, in the asthma market, most of the endotypes are driven by eosinophil level, and if in fact, you know, we can lower, abrogate, reduce, that eosinophil level, then does that mean briquilimab could be used across all of the endotypes? And the last thing that will be really interesting, I'm not sure we'll learn it from this first study, but certainly have the opportunity to in the phase two.
So mast cells are very much also involved in the remodeling phase, and if we're able to impact that in the remodeling, if you put all that together, a logical next place to go could be to go into COPD. So again, we don't view this as just a derm drug. We think that there's broad application wherever mast cells are you know mediating or driving that disease.
Great. Maybe just to sum up, just discuss upcoming catalysts that you're expecting in the next, say, 12 months.
I think the one that we're laser-focused on in the company, and I think most of the people in the room probably are also, is our data readout in Q4 this year from the CSU BEACON study. Also with the data around the CIndU SPOTLIGHT study FPI and the asthma study in Q4 of this year, and then a likely presentation of the CSU and CIndU at a scientific conference early next year, and then middle of the year, second half of the year next year, the asthma readout.
Great. Okay, thank you very.