Welcome to the Cantor Global Healthcare Conference. I am Pete Stavropoulos, a biotech analyst with Cantor. With us, we have Jasper Therapeutics, a company I cover, and I'm pleased to introduce Ron Martell, the CEO, so welcome, Ron, and let's start off with an introduction of yourself and a brief description of Jasper for those not familiar. Pete, well, first, on behalf of all of my colleagues at Jasper, we'd really like to thank Cantor and you for all of your support. Yeah, so Jasper Therapeutics, we are a clinical-stage biotech company. Our lead asset is a monoclonal antibody, briquilimab, we refer to as BRQ, and it targets KIT on mast cells, and we are currently conducting a number of clinical trials in urticarias. Can you just give us a brief background on briquilimab, sort of where it came from and how it ended up in your hands? Sure. So briquilimab was originally designed and put into the clinic by Amgen. They specifically designed this antibody to target KIT on mast cells. Having said that, they were originally exploring this antibody in IPF, or pulmonary fibrosis. And what we all know now is that while there are mast cells involved in that disease, they're not the primary fibrotic mechanism, and depleting mast cells doesn't reverse that. So we're the beneficiaries, though, of a well-designed antibody by Amgen, and we've now taken that forward into multiple clinical trials in urticarias. All right, so you mentioned it doesn't play a role in IPF, but what role do, I guess, mast cells actually play in CSU and CIndU? Yeah, so mast cells are the primary mechanism for diseases like urticaria. They play a critical role in asthma. There's probably 20 to 30 different diseases, prurigo nodularis, others that mast cells are involved in. But mast cells in the skin are the underlying cause of diseases like urticaria. And importantly, mast cells, they release granules, histamine, other things that create these hives, wheals, and significant itch that are known in diseases like urticaria. And what we know is that by using an antibody like briquilimab to target KIT, KIT is the primary survival pathway on a mast cell. And if you shut down KIT, you shut down all phosphorylation, and you'll trigger the mast cell to undergo programmed death or apoptosis and leave the skin. And that then has significant clinical benefits for patients for an extended period of time. Okay, so it affects the survival pathway, and I guess, you know, part of your approach is depletion of mast cells. And so, you know, when you think about some of your competitor programs, either antibody-wise or alternatively small molecule, how do you see, you know, how do you see those sort of programs playing out in terms of efficacy, especially the small molecule approach? Sure. Well, first of all, it's good to see in the field that there are, in the future, there will likely be multiple treatment options for patients with CSU, where for decades they've really only had antihistamines or omalizumab. So having some therapeutic options will be important for the field. Having said that, there's only one approach that depletes mast cells, and that's an antibody to KIT, like briquilimab. All of the other approaches, the small molecules, they only inhibit the mast cell. So you need to have inhibition of that mast cell 24/7, 365, or the symptoms will come right back. So with an approach like briquilimab, it translates into a superior clinical benefit for these patients. So do you think a small molecule c-KIT inhibitor may not lead to, I guess, efficacy or depletion? So the small molecule KIT programs that have been in development to date haven't shown that they can deplete mast cells. Even when they're dosing to, say, like IC90s, they're only achieving inhibition of the mast cell. And we know that because they're lowering tryptase, but as soon as they go below a concentration of any sort of level, then the clinical symptoms come right back. So that tells you that the mast cells are still there because the tryptase comes right back and the symptoms come right back. Okay. So I think it'll be a challenge. Somebody hopefully will figure it out. But it's been a challenge to date to get high enough concentrations inside the cell, avoiding the off-target or on-target adverse events to be able to truly deplete mast cells with a small molecule. Okay. All right, you do have two key studies underway with briquilimab, the BEACON study in chronic spontaneous urticaria and the SPOTLIGHT in chronic inducible urticaria. So starting off with BEACON in CSU, you know, you've shared data from several dosing regimens. Can you just walk us through the study design, including the time point when efficacy measurements were taken, sort of the total treatment period and the time point, you know, when subjects will actually roll over to the OLE? Sure. Well, it's important to keep in mind in looking at the design of the BEACON study, the biology of the mast cell and the properties of our antibody. So we talked about the fact that depleting mast cells and with an antibody you can do that like briquilimab, and it also takes a while for mast cells, once they're depleted, to return to the skin. And so we've taken an optimum biologic approach to drugging this disease. And by that, I mean we're focusing on what's the concentration of briquilimab to initiate that apoptosis. Our half-life is only about nine days, so we want to clear the antibody out, clear the antibody out to avoid the on-target adverse events and not reintroduce the antibody until right before the clinical symptoms start to come back or before the mast cells return, thereby giving patients as long of a drug-free interval or an opportunity for signal to be regained to other cell types that also present KIT. With that in mind, we designed the BEACON study with a number of cohorts that are looking at different dose levels and different dose intervals. What we've now learned about the disease and about briquilimab is that it looks like the optimum dosing schedule for briquilimab is every eight weeks. When we dose at 180 milligrams and above, we see very rapid reduction and clinical relief. In two weeks, we see complete responses, meaning that these patients, they're entirely, their hives, their wheals, their itching are gone within a brief two-week period of time. And we see that duration of that efficacy lasting through approximately eight weeks. So with that in mind, our drug antibody has a half-life of about nine days. The antibody is completely cleared. So when we redose the patients at week eight, we can maintain or keep that clinical benefit and minimize, reduce, or potentially eliminate the unwanted adverse events. Okay, so you know, I was going to ask you to start off with a 120 milligram dose and the 180 milligram dose once every eight weeks, once every 12 weeks. I think you presented that data at Quad AI. So you did talk about the 180 a little bit, you know, but 180 in Q12 weekly, and also discussed the 120 milligram data. Yeah, so the 120 milligram data were really interesting. Again, even at 120 milligrams, we saw a very rapid reduction in the UAS7 score in these patients. However, we were dosing it at every eight weeks, and what we know now about the drug and with the half-life is that 120 was very effective in those first few weeks, but with those concentrations, the clinical symptoms started coming back between week four and week six, so if we were to use 120 moving forward, it would likely be a Q4 week dosing regimen. Having said that, when we moved then up to the 180 and then ultimately to 240, we saw a more rapid reduction in the clinical symptoms and a deeper reduction in the UAS7 scores, with no significant increase in the KIT-related adverse events, giving 180 at every eight weeks or the 240 at every eight weeks. It tells us that we have a better dose than 120 every four weeks, which isn't very convenient for patients, and a better clinical response if we were to give 180 every eight weeks or 240 every eight weeks. Great. You did have a single dose as well as 360, and what did you see there? Sure, so yes, we've dosed 360 milligrams in patients as well as a single dose, and what we observed there was, again, complete responses in three of the four patients, so really good clinical response. Having said that, that efficacy is no different than what we see with the 240 milligram dose level, so it tells us that there isn't a need, there isn't a benefit to go up to 360. We don't need to go higher than 240, and likely we'll just end up with an increase in the KIT-related adverse events by going that high. So when I do look at the graph for the 240 and 360 single doses, what I do see is that the 240 sort of hugs the UAS7, you know, at the zero marker for, you know, out to about seven weeks, and 360 hovers at about five out to week eight. Just, can you help us understand, was it a single patient that drove that, you know? Yeah, it was. It's It's an artifact of a small n. So there were only four patients in that cohort, and three of the four patients achieved a complete response down to zero, like you stated with the 240. And there was one patient that didn't. So because it's a small n, visually it makes it look like there's a separation in the lines. Okay. And now you also reported preliminary outcomes for the open label extension. You know, where patients were receiving 180 milligrams every eight weeks, I believe it was 11 subjects' worth of data. Which cohorts did these subjects come from, and did they roll over immediately after placebo, controlled portion of BEACON, or was there a time lapse? So we do have an open label extension study in BEACON and in the SPOTLIGHT study from the CIndU study, but specifically in BEACON, all patients are eligible to enroll in or roll over into the OLE once one of two things happens. Either they've completed 24 weeks on the BEACON study, or if their UAS7 rises above 16. So if they had a clinical response to briquilimab, then unfortunately, the way the study was designed, they need to come off of briquilimab, their disease needs to come back, their UAS7 needs to go up above 16, and then they're eligible to roll over into the OLE study. We reported on the first 11 patients in that study. I should say that by the end of the year, we will have approximately 40 patients that will have at least 12 weeks' worth of data on, and we should have in the neighborhood of 25 or more patients where we'll have more than 26 weeks of data on from the OLE, so what that tells you is that the vast majority of the patients, and I believe all but two of the patients who have been given the opportunity to roll over into the open label extension have done so, and those two that did not, they went on to a different protocol, and during the time where their disease needed to come back, they chose to go into another protocol. Otherwise, all the patients are selecting going into the open label extension. Okay, and what was the rationale behind actually letting the patients have, I guess, a drug holiday if they did have a low score on the UAS7? It was the original design to see what we wanted to do two things. We wanted to be able to, in the original design of BEACON, we wanted to see if you stopped taking briquilimab, how long would it take for your disease to come back? So if you're after multiple doses, and so patients will have all received at least three doses of briquilimab before they would roll off of BEACON and potentially roll into the OLE. And we wanted to see how long it would take for their disease to come back if we're meaningfully depleting the mast cells in their skin. So that was the original concept behind it. And then we wanted to make certain that the disease came back to above 16 so that they have moderate to severe disease so we could see the effect of repeat dosing in 180. So it was 24 weeks of treatment, correct? That's correct. So what do you think will happen when you have longer periods of treatment, 48 weeks, 52 weeks, you know, two years? Do you think there's a possibility of some type of immune reset, if you want to call it? You know, I think that, well, first of all, we know that mast cells are the perpetuating cell, and so depleting mast cells is key here. We also know, at least from looking at Celldex's data, that they get a deepening response with more doses. Now, that may have to do with potency, not quite sure, and it looks like they reach a maximal effect of about 75%. But what we also know is that this is a disease where the mast cell is the perpetuating cell, but the mast cell is not diseased. It's a normal mast cell like you and I might have if we don't have CSU, but something in the immune system is triggering the mast cell. So you have a hyperreactive immune system, and depleting the mast cell may not be enough initially, and it may take a while for the immune system to calm down, and that's maybe why we see late responders. Now, on the back end, what we may find is that after you've depleted the mast cells for a prolonged period of time, you may have quieted down that immune system to where you, I wouldn't say that you've cured the disease, there's no evidence of that, but it may take longer or the disease, when it comes back, may be less severe. Okay, so you know, I know there's more data to come, but from the totality of the data you've generated to date, you think there's basically two possibilities in terms of a dosing regimen, which is the 120 as a Q4 and the 180 as a Q12, correct? I would say that based on the totality of the data, and especially the data from the OLE study in that N of 11 you described, it looks absolutely superior. With 180 milligrams given every eight weeks, at a 12-week endpoint, and looking at the UAS7 scores, we had 73% of the patients who had a complete response and a total of 82% of the patients that had well-controlled disease. Nothing in the field even comes close to that. So we're really pleased with the 180 milligram Q8 week dosing right now, and that's likely one of the doses we'll take into our phase 2b study. The data that's coming later this year that we're really interested in is the 240 every eight weeks, and it may be even more interesting than that, though, is the 240 followed by 180. So if we get a deeper response and a rapid response with the 240, what if we backed off and now did the maintenance dose of the 180? So by the end of the year, we'll be able to pick those two doses, but the 180 Q8 week looks like an absolute winner. All right. So I guess one of the things that you were trying to do is, you're trying to do with briquilimab is to, you know, thread the safety and efficacy needle. How does the 180 once every eight weeks, once every eight weeks look? Yeah, the safety profile looks very favorable. To date, on all doses of briquilimab, all the way up to 360, all of our KIT-related adverse events have been mild, transient, and self-resolved before the next dose. That's really important. So what we're seeing here is that even if you might have hypogeusia or a loss in taste, we've seen that in a few patients that it seems very transient, resolves in about 31 days for those patients that observe that, and they go on to their next dose either without incidence or without an increase in severity of those KIT-related adverse events. So the safety profile looks very, very favorable and very differentiated. Okay. Then when you do look at your data and you stack it up against your competitor, Barzo, you know, for efficacy and safety, sort of what's your, I mean, they're small n's, but your initial sort of perspective? Yeah, from an efficacy standpoint, that data that I just described with the 180 mg of 73% complete response at 12 weeks and 82% overall disease control compares very favorably to about 50% complete response at 12 weeks with barzolvolimab at 150 milligrams every four weeks or 38% complete response with Barzo at 12 weeks with the 300 milligrams every eight weeks. So more than double-digit improvement in complete response over barzolvolimab. And when we look at the safety, what we know, again, there's significant difference in half-life, nine days versus about 22 days. What you see with Barzo is not only do you see a higher incidence of KIT-related adverse events, you see an increase over time when you look at the difference between their initial data that was reported at 16 weeks versus what was reported at 52 weeks. In some of the cases, there was more than a doubling of the KIT-related adverse events, and that's because they constantly have drug on board. Okay. So just we have about five minutes left. You know, when we were supposed to see data for 240 milligram once every eight weeks and 240 followed by 180 every eight weeks, you know, mid-year, I was confounded by some issues. I guess one drug lot was, I guess, compromised. You know, any updates on that, and was it limited to one lot so far? Yeah, so yes. So we did have two cohorts, cohort eight and cohort nine, which is cohort eight is the 240 milligram every eight weeks, and cohort nine is 240 milligrams followed by 180 Q8. Unfortunately, the results there were confounding. They were dissimilar to everything we had observed. We saw patients who had no change in their UAS7 score. So we initiated a comprehensive investigation, and one of the first things we observed was that all 10 of the patients in those two cohorts received drug from a specific lot. So that was one of the first things we wanted to look at was there something unique about this lot, or did something happen to this lot of drug that could have affected the clinical outcome? And in this investigation, we've gone all the way back to the raw materials through drug substance, drug product, through the cartoning and labeling, all the way through to the patients. And what we know now, and it's very comforting to know, is that there's absolutely no issue with our drug substance and drug product. Our core manufacturing passes all spec, and all the drug is fine. We're now really focused on what I'm referring to as the last mile, although it's certainly a lot more than one mile. But so when the drug leaves the third-party logistics company who does the cartoning and packaging for us, all the way through the patients, we're looking at all aspects of shipping and ultimately drug administration, ensuring that the proper needle was used, the proper administration from sub- Q. We'll be looking at the PKPD from these patients, and we'll be looking similar to what we saw in January and what Celldex has obviously observed in their trials, that probably one in four, one in five patients don't have mast cell mediated disease. So maybe that's what we will see here also is that we're unlucky that, you know, some of these patients didn't have mast cell mediated disease, but we'll find that out. We'll have a full dossier on site audits from these sites and these 10 patients to know exactly what happened. But importantly, we're already redosing those 10 patients, and we're enrolling 10-12 new patients in those cohorts as well. So the patients that you're redosing, they're not part of the blinded study? They're part of the blinded study. Oh, they are? That's correct. Yes. Just put an open label and see if they're responding. So they remain, the patients and the physicians remain blinded to this study. Well, we're blinded to it as well, but yes, the redosing patients, redosed patients are blinded. Did any of the OLE patients receive this drug lot? No, they did not. Okay, so you know, you do have more data coming by the end of this year. Can you just lay out what the plan is for presenting the data? Sure. More than likely, you know, it'll be a company-sponsored event similar to what we've done in the past, and then potentially a scientific presentation at maybe Quad AI. That's sort of the obvious one with timing here, but yeah, so we look forward to, by the end of the year, having those 40 plus patients in the OLE with at least 12 weeks of follow-up, 10-12 new patients in cohorts eight and nine, the retreatment of the patients in cohorts eight and nine, as well as the asthma study, the data from the asthma study. We'll have that by the end of the year as well, and we'll have the results of the investigation. But the asthma study, if I remember correctly, they have the compromised, theoretically or possibly compromised drug lot? They received drug from the same lot. That's correct. Okay. But we'll be able to look at all of those patients as well. But again, really want to stress that, you know, there's no evidence that the drug product, drug substance coming out of our manufacturing facility is compromised. It looks good. All right. Have you looked at tryptase levels? We're looking at the tryptase levels. So when we looked at the initial analysis of the data on these 10 patients, we saw PK that was similar to what we've seen in other cohorts. We did see a reduction in tryptase, although the tryptase reduction wasn't as deep as what we've observed in the past. Having said that, again, this is where, you know, unfortunately with small numbers in these cohorts that we've also seen in the past where it takes, you know, a week or two or more for the tryptase levels to go down. So we'll want to see what happens on redosing here. Okay, well, we are out of time, but before we end, if we're sitting here a year from now, what would you like to say were the key value-creating accomplishments for Jasper? Certainly these data, these data, and getting to a sample size that is significant to basically wash out some of these questions and selecting our doses for the phase 2b study, launching that phase 2b study. All right. Ron, thank you very much for participating and for Jasper participating in the Cantor Healthcare Conference, and so looking forward to the updates and best of luck. Thank you, Pete.