Great. Good afternoon, everyone. Happy to introduce Ron Martell, CEO of Jasper Therapeutics, with us today. I think in lieu of a presentation, we're just gonna sort of do a fireside chat. Maybe, Ron, do you wanna kick things off with a brief overview of the company, and then we'll get into it? Sure. First, on behalf of all of my colleagues at Jasper, I'd love to thank Alex and the Stifel team for all of their continued support and the opportunity to be here today. Jasper Therapeutics, we're a clinical stage biotech company. Our lead asset, briquilimab, is a monoclonal antibody in clinical trials in chronic spontaneous urticaria, chronic inducible urticaria, and asthma. We've had significant readouts earlier this year, and we have data coming here in Q4 and early next year. Our antibody binds to Kit, and Kit is the primary survival pathway on mast cells. We understand that if you inhibit Kit, you shut down all phosphorylation and, importantly, mast cells apoptose. It is a key mechanism and primary target in the INI space. Yeah. I think I wanna start off with just sort of an overview of where the urticaria landscape is today. I guess in particular with, you know, launches of remibrutinib and DUPIXENT, how do you expect that to evolve over the next, you know, 5+ years? Sure. So first of all, really happy for CSU patients that they finally start to have some choices. It's been decades, where their only options were antihistamines or omalizumab. Mm-hmm. And so now there are some choices for patients. Maybe I'll start with an oversimplistic or overly reductive approach to it, but you can either inhibit the mast cell or you can deplete mast cells. Mm-hmm. To date, the only approaches that appear that look like you can deplete mast cells are with an antibody like briquilimab or with barzolvolimab. All of the other approaches only inhibit the mast cell, thereby needing to maintain 24/7, 365 inhibition, or the clinical symptoms will return as soon as that therapy is cleared. We think that depleting mast cells is the superior mechanism for efficacy. If we can chronically give these safely, and we think based upon the properties of briquilimab, specifically the half-life. Yeah. that we only have a nine-day half-life, that we get that concentration to initiate the apoptosis and clear the antibody, then we can have a superior safety profile. There'll be choices for patients in the future, but if you wanna deplete your mast cell and have a prolonged efficacy experience. Yep. Likely, briquilimab will be the superior choice. Yeah. I think this idea of depletion, I think there's obviously, as you're alluding to, there's degrees of depletion. Are you using a sledgehammer? Are you being a little bit more selective about it? I think that goes to the fact that Kit's not just expressed on mast cells as well, right? Can you talk a little about this idea of therapeutic index and half-life and design of briquilimab, like how you're trying to thread that needle? Sure. So again, with a mast cell, we know that Kit is the sole survival pathway. If you shut down phosphorylation, you shut down FOXO3a, BIM's unregulated apoptosis takes over. If we're able to do that, with that understanding, then drugging a mast cell all comes down to a Cmax, not AUC. Kit, as you say, Alex, is present on melanocytes, on taste buds, on stem cells. Importantly, there's no evidence in those cells that Kit is the sole survival pathway. Clearing the antibody so you can restore signaling to those cells is critically important. If you look at our data that we've generated, and as an example, if we take the stem cells and if we look as a biomarker, look at the neutrophils, we do see a small dip in the neutrophils on initial dose. Then we see those neutrophils start to rebound at about week four, which is consistent with the half-life of the drug. If you're thinking about neutrophils being a biomarker for the stem cells or maybe even the melanocytes or others, maybe we're restoring the SCF signal back to those cells as well. Now, if you're using a small molecule or even barzolvolimab, because barzolvolimab's half-life is about 22 days. Yeah. With their dose and schedule, they're never giving those cells an opportunity to restore signaling. We are starting to see a differential safety profile play out where we're seeing a lower incident rate of those Kit-related adverse events, and we're seeing a lower severity of those events as well, because again, the antibody is clearing, giving an opportunity to restore signal. Yep. And, you know, obviously there's the, there's the dosing, the half-life here. You're mechanistically a little bit different too, in the way that you inhibit Kit activation. Is that a key element of differentiation in your view versus barzolvolimab? I think so. It, you know, it certainly appears as if briquilimab is more potent than barzolvolimab. Now, we have not done head-to-head, and so, you know, you can compare IC50s or IC90s or whatever you want to compare, but unless they are done under the same conditions, you cannot really tell. Having said that, when you look at the efficacy of briquilimab, you see a much more rapid and deeper response to a single dose of briquilimab than what you do to barzolvolimab. That may be in the design of the antibody. Yeah. Briquilimab is classically designed to bind to the epitope of the natural ligand SCF. Yeah. Barzo, on the other hand, is an anti-dimerization antibody, so binding further down the stalk. That historically in antibody development has conferred a differential in potency. Okay. Now, you've alluded to some of the clinical data you've generated, but maybe starting with CSU, can you walk through your clinical program and, you know, the data that you've generated to date, both? Let's start with, you know, efficacy. Sure. Our primary study in CSU is a study we've referred to as Beacon. Beacon is a classic dose escalation study, but it goes beyond that because this is one place where it's good to be a fast follower. We learned a lot from barzolvolimab's development. Prior to there being in the clinic, there had never been a drug that could deplete mast cells. It wasn't really well understood what it took to deplete a mast cell or what the kinetics are for the mast cell return. We also designed this study looking at different dose levels as well as different dose intervals. What we've now learned is that 180 mg and above with briquilimab gives us what appears to be superior efficacy. We've learned that briquilimab is an eight-week antibody with dose levels above 180 mg. At the 240 mg level, we got 100% complete responses. It was an n of five, but we got 100% complete responses, and those were durable through eight weeks. That is why we have a couple of additional cohorts that'll be coming. We announced in the press release yesterday that in the first half of Q1, we'll have that repeat dosing data looking at loading with 240 and then either followed by 240 or followed by a step down to the 180. I think it makes sense, right, that your clinical efficacy is looking, you know, at least the same as barzolvolimab at this point. I guess on safety, you are still seeing neutrophil reductions and other on-target Kit-adverse events. You know, how much more data do you think that you need to, you know, prove out this differentiation on the safety side of things? I think the data that will be coming in Q4 will be really important. Yeah. In Q4, we will have, for the very first time ever, multiple repeat dosing with 240. Yep. We'll have eight or so patients that will have received at least two, and most of them three doses of 240, Q8 week. That will give us a really good indication of what a significant dose of briquilimab looks like from a safety standpoint. Having said that, on all of the other doses, we now have better than six months' worth of follow-up on safety. The incidence profile looks lower than that of barzolvolimab. Importantly, the grade and severity do as well. Let's take the neutrophils as an example. Sure. When we have seen a decrease in neutrophils, what we've seen though is a median time to resolution of the decrease in the neutrophils of only 15 days. That again is very consistent with the half-life and the clearance. It's a mild transient dip in the neutrophils, and then they rebound. Yep. Makes sense. Maybe, you know, I wanna get to the Q4 data, but can you take us back and sort of go through what happened in July and with the dosing and some of the initial data there and what you've done to elaborate what happened there? Sure. In July, we announced data from three different cohorts. The one cohort, and we'll talk more about this, was from the OLE or open label extension. In that study, we gave 180 mg Q8 weeks. In the first 11 patients, when we looked at that data, they were quite remarkable. We had complete responses of 73% and a total well-controlled disease of 82%. Comparing that to barzolvolimab, which had about 51% and 38%, so significantly better than that of barzolvolimab. We'll have an update on that in January. I'll talk about that in a moment. The other two data sets that we released in July were around what we refer to as cohorts eight and nine, which were 240 Q8 week and 240 followed by 180 Q8 week. Unfortunately, in those 13 patients, we had two patients in the EU that had complete responses. and then in the U.S., we had 10 patients, at five centers who had no clinical response, and completely anomalous to anything we've seen, in the past. That made us step back and initiate an investigation. The investigation initially focused around the drug product. First question we asked was, did somehow these patients get shipped placebo? We looked at the PK on these patients and no, in fact, the PK looked very similar to the PK that we had seen at these dose levels in the past. That's only a partial answer, because we, you know, the PK is just showing that there's antibody on board, but maybe that antibody had denatured, had fragmented, so we needed to do more work beyond that. Then we looked at the tryptase levels, and the tryptase levels were down, consistent with what we've seen before. That meant that they had active antibody on board. We did not stop there. We went and recalled drug from the site that had actually been used in these 10 patients. We took drug that was stored at the third-party logistics company. We went back to the CDMO and we recalled samples from the DS and the DP. We shipped all of that drug in a blinded fashion to a third-party lab who ran an entire battery of tests to determine that there was no difference in the drug that was given to these patients from any drug that was stored anywhere or made along the supply chain. That gave us good comfort that there was not an issue with the drug product. We then extended the investigation to, we hired a CRO to go out and do a site audit. They audited these five sites, and we hired that same CRO to do an audit of all 10 of these patients. That's what we'll have coming here in Q4 is the final summary of all of that data. We're pulling together a panel of three KOLs to do a review of all the data and give their summary of their findings. Mm-hmm. Right now, the leading hypothesis is, it may be as simple as, or it may be multifactorial. It may be that these 10 patients don't have mast cell-mediated disease. Mm-hmm. It could be that, you know, there was something related to the injection or the injection site affecting bioavailability. It could also be that maybe we end up seeing some patients who are late responders, but we'll be able to draw the investigation to a conclusion. Fortunately, we know it's not related to the drug product. Okay. So then that's part of the broader 4Q update. What is a good outcome, you know, with your 4Q update more broadly? A good outcome of that investigation is, first, as I alluded to earlier, a clean safety profile with redosing the 240. Because even if these 10 patients do not show efficacy, we know that they are getting active drug, so the safety. Yeah. will be absolutely interpretable. The other good outcome from this is, a conclusion from an independent group of KOLs that say, you know, maybe these patients unfortunately don't have mast cell-mediated disease. As one other KOL has said to me, he said, you know, we've been looking for a diagnostic for CSU for decades. Yeah. Maybe we found one in briquilimab because if you do not respond to briquilimab, you do not have mast cell-mediated disease. Yeah. We'll see, and we'll be looking forward to putting this chapter behind us. The other important thing to note is that when we saw these results, we immediately, because we weren't sure about the drug, we immediately recalled that drug, not for safety reasons. I use the word recall. Maybe I should say we immediately told sites to not use that drug. We shipped them drug from a new lot. Yeah. All of those patients were being retreated with a new lot. We began enrolling new patients into those cohorts. Okay. And that is what we're gonna get in the first quarter of next year? What we'll get in the first quarter of next year is, in the first half of the first quarter. Yeah. Is we'll get the data on the new patients. Yeah. That are enrolled in those cohorts. We'll get even longer-term follow-up than on the redosing of those patients. Okay. and we'll also be getting more data on the OLE. Yep. Those 11 patients that I alluded to that efficacy. By the time we get to the data set, in early Q1, the N in that study, in the OLE study, will be approaching 40 patients. Yeah. Our largest cohort to date, where we'll have around between 35- 40 patients, where we'll have at least 12 weeks of follow-up on the 180 Q8 week, and probably about half of those patients where we'll have 24 weeks' worth of follow-up. For both efficacy and safety, we'll have that data. In addition, we will have the update from the OLE in CIndU and inducible urticaria. Previously, we've reported on single agent use in urticaria. Yep. had, that was reported at EAACI this summer. Very significant efficacy results there seen with a single dose at 180. And when we update that in Q1, we'll have 15-ish patients that will have multiple doses at 180. Yeah. I guess you're thinking about the data in the first half of the first quarter. Is efficacy, you know, is efficacy need to be better than barzolvolimab? Does safety need to be better than barzolvolimab? If you have the same efficacy but better safety, is that a sufficient profile for you? How are you thinking about kind of, you know, what the product profile might look like? Yeah. So I think that, comparable efficacy, is, is a winner. I mean, we're just, we're a fast follower, right? Yep. Better efficacy is a better win. Efficacy that's comparable or better with a better safety profile is a clear. Sure. That's a home run. Moving forward now, what are the next steps here moving into a 2B/3 in CSU? We've guided to starting the phase IIb study in the middle of 2026. Mm-hmm. We know that we have an efficacious drug. The objective for concluding Beacon and the objective for the phase IIb is really putting two efficacious doses into the phase IIb so that we can come out of that phase IIb with a single dose to take into the phase III that we know has been optimized for both efficacy and safety. Yep. Because we think we have an opportunity to win on both of those. How many doses do you think you need to bring into IIb? Two doses. Two doses. Is there an opportunity for you to accelerate CIndU development as well at this point? There is. However, we, we, so first of all, we think, and this is where we agree with Celldex, that the same dose that's used in the CSU trial is the dose that you'll use in CIndU. Yep. As a reminder, in these diseases, the mast cell is actually not diseased. Something in the immune system is, but the mast cells are not. Whatever dose it takes to deplete, inhibit the mast cells in these diseases is the same. The dose we choose for CSU will be the same dose we use for CIndU. We think from a development standpoint, though, CIndU will be a lot easier because we will be able to rely upon the safety database that is generated in CSU. There strategically, there is not a real advantage to, quite frankly, the spend on starting that study in parallel with the CSU. What our objective is, is to have those lined up so that they conclude at the same time, because the CSU trials will be dramatically overpowered for efficacy. Yep. You need a certain safety database. Again, this is where we think we have an opportunity to make up some time on Celldex. They took two doses into their phase III, which meant that they need a total safety database in around 2,100 or 2,200 patients. If we take one dose into our phase III, that means our safety database is only 1,200 - 1,500 patients. We potentially are enrolling 500-700 less patients than what they will need, than what they are enrolling. Makes sense. On the broader competitive landscape, your, what are your thoughts on MRGPRX2 as another way to, you know, block mast cell activation in this space? Is that a major competitor for you? I think it's an interesting target, and I think it probably will find its place into the armamentarium. I think, maybe sort of, to my earlier comments that I haven't seen data that would suggest that blocking MRGPRX2 will deplete mast cells. Yep. I think it. More strategy, EU-like than Kit-like. Yeah. Yeah. I think it will fall into more of that inhibitory realm. Yep. I think the other thing too, with whether it's X2 or any of the other approaches, is how do you identify a biomarker or test. Yep. To ensure that that patient's disease is driven by X2? Yep. Yep. Makes sense. I guess, you know, the other strategically interesting question here is if you end up with a profile that might look similar efficacy than barzolvolimab but maybe better safety, you think you're gonna have enough safety data to differentiate that on the label? Or do you think you're kind of potentially destined to share a label with barzolvolimab and that? Yeah, I think that these therapies will likely be judged on their own safety profile. Yep. You know, the good and the bad of what the agency requires for approval for these types of therapies are a very substantial safety database. Yep. Again, 1,200-1,500 patients where your safety profile will be easy to interpret, from a class effect. Yep. Makes sense. And then I wanted to talk about cash runway. Where are you at today? What's in your current assumptions? We have cash, into the third quarter of next year. Yep. We have enough cash to complete all the activities I just described, as well as all the prep work for our phase IIb study. Mm-hmm. We have drug supply already made for that study. We would need capital, though, to execute that study. Yep. That study, that we're contemplating is not dissimilar to what Celldex did also. Yep. you know, a total N, three arms of about 100-ish patients. so we'll, we'll be contemplating what are our options. Yep. you know, that could include a capital raise. It could include some type of clinical co-development, type of financing. It could include, you know, something more strategic. Yep. This is Kit is a hot target in the INI space. Yep. We'll see how that plays out. I guess for you, you know, if you had the capital, is asthma still an interesting label expansion opportunity, or would you take the opportunity to look at some of the phase II readouts next year and think about other indications to go after? Yeah. We will be reading out the initial results from our asthma study here in Q4. Yep. I think that will be interesting. It's an early proof of concept study where we're really testing the underlying biologic question of if you can deplete mast cells in an asthmatic patient, will that have any impact on their disease. We'll get some early signals from that in Q4. We're keenly interested in that disease. I think, interestingly, as you probably would expect, that's something that's a really large market opportunity that's high on strategic's radar. Yep. I think that's an indication that's begging for a partnership. Yes, to your point, we're keenly watching the development, you know, whether that be from Celldex or others. Yep. Fortunately for us, again, this is where it's good to be a fast follower. Celldex told us and taught us not to go into EOE. And they've taught us that PN is a, is a great place to go. Yep. We're keenly watching all these developments. Great. Ron, thank you very much. Thank you.