To 2025 RBC Global Healthcare Conference. My name is Suphawat Thongthip, the Assistant Vice President, and we are pleased to have Jasper Therapeutics with us today. Joining us is Ron Martell, the Chief Executive Officer. If you have any questions, we have a quick Q&A at the end for the team. Thank you, Ron, for joining us today. Obviously, an important year for Jasper, and we're going into an important data point later on in mid-2025. Very exciting. Maybe just to get started, could you just give us a brief introduction about Jasper for those of us who are less familiar? And perhaps maybe an outline of the significance of c-Kit as a therapeutic target in early carry and maybe in the broader information and immunology RNI.
Sure. First of all, Suphawat, on behalf of all of my colleagues at Jasper, thank you to you and the RBC team for this opportunity to be here today. We really appreciate that. Yeah, so Jasper Therapeutics, we are focused on mast cell-mediated, mast cell-driven diseases. Our lead asset is a drug called briquilimab. Briquilimab is a monoclonal antibody specifically designed to target c-Kit on the surface of mast cells. Our antibody has a high affinity and avidity for that receptor. What's really important here is to understand that basic biology. c-Kit on a mast cell, and c-Kit is on a few other cell types in the body, like melanocytes, taste buds, stem cells. We'll talk about that as it relates to safety in a moment. Specifically, c-Kit on a mast cell is the primary survival pathway on a mast cell.
If you shut down c-Kit, you will make the mast cell apoptose. That is the key here, and that is the mechanism of action here. Shut down that phosphorylation, you shut off FOXO3A. BIM then is upregulated, and it tells the mast cell to have an orderly and programmed death. That is really important as it relates to mast cells also, because the last thing you want to do is to trigger mast cells. That is what we are trying to stop in most of these diseases. It is really fortunate that it is a very clean mechanism, and that is what we do with briquilimab.
Got it. Got it. Yeah. Maybe we can just dig right in. Briquilimab's main program is in chronic urticaria, chronic spontaneous urticaria in particular, or CSU. Maybe let's just dig right into the BEACON study. That's the phase I-II study of briquilimab in CSU. Could you remind us of briquilimab's data in that study so far? What you've learned from that study so far?
Sure. We designed BEACON to really explore optimal biologic dosing. We think, especially in these mast cell-mediated, mast cell-driven diseases, that that really is the way to treat and to drug these diseases. Again, biology, we know that shutting off the mast cell depletes the mast cell. Mast cells then will regenerate and repopulate the skin. Briquilimab has a half-life of only about nine days. If we lean into that biology, we can get the drug on board, deplete those mast cells, clear the antibody out before we redose. Why am I explaining all this?
That's how we designed the BEACON study, was to look at a range of both dose levels as well as dose intervals to teach us what's that optimal dose to deplete those mast cells and what's the optimal interval of time to reintroduce briquilimab and at what dose levels. Because as I touched on a moment ago, c-Kit is present on other cell types, so you can get these c-Kit-related adverse events if you're constantly blocking those other c-Kit cells. We tested it in BEACON to look at all these different doses to give us that information. Specifically, the data that we presented in January, the first initial handful of cohorts from this study looked at dose ranges from 10 mg all the way up to 240 mg on one dose or every eight weeks or every 12 weeks.
What we've really learned from that study is a few things that are really exciting. One is that briquilimab has a very rapid onset of clinical relief, and that matches the PK in the drug. When we look at the PK from the study, within a week, the Cmax is reached with briquilimab. It gets very rapidly from that subcutaneous space, the subcutaneous tissue through all five compartments to the target cells. We learned that briquilimab rapidly brings relief to these patients and that the durability of that relief or complete responses seen in these patients corresponds to that half-life that we talked about a few moments ago. Some really important data where we saw between 50% and 100% complete responses in these CSU patients that at the 240 level were durable for eight weeks.
Yeah, I mean, that's a really interesting data point. I think you were referring to the data point at the 240 mg dose cohorts, right? And that's 100% complete response that you achieve by week two, and it's sustained into week eight. Just maybe help us contextualize that treatment effect, you know, compared to other therapies. And perhaps maybe have you speculated as to the mechanism underlying this rapidity onset of effect and durability?
Yeah, so the data we've generated look better than anything to date, whether that's the small molecules, omalizumab, barzolvolimab, the only other antibody in this space that targets c-Kit. And they've had remarkable data. It's important to note when I make that statement, you know, this was a small sample size. So I hesitate to have cross-trial comparisons. We're very pleased with the data we've generated. A high portion of the patients, you know, upwards to 70% or 100% with complete responses that were durable and well-controlled in the other patients that didn't receive a complete response. So, you know, upwards to that 70% of all patients either have a complete response or their disease is well-controlled. And again, that durability really matches the dose, the 120 mg. That durability looks like it's about four weeks. The 180 mg is probably somewhere in that six weeks.
The 240 is eight weeks. So we've learned a lot about briquilimab and mast cells in the BEACON study to date.
Got it. I mean, yeah, of course. That's why we are hoping to see more, I think, in the mid-year update. Maybe I think that's one point of confusion in the January dataset in terms of maybe perhaps the lack of dose response between the 120 and 180. Just, I mean, wondering if you could help maybe clarify this. You know, what's your thought? What's going on there? I think that would be helpful.
Sure. Yes, I think what you're referring to is specifically the 180 mg Q8 week cohort. Again, on PK, there was a very nice dose response in the patients. Tryptase, the same thing, very nice dose response. In fact, at the 180 mg on the Q8 week, all of those patients, their tryptase went below the lower limit of quantification or LLOQ. It was very clear that briquilimab was depleting the mast cells in these patients even at the 180 mg Q8 week. The confusion came when you look at the complete response in that cohort, that it was slightly less. About 43% of the patients in that cohort had a complete response, where the 120 Q8 week had about 50% of the patients had a complete response. Optically, it looks like in that cohort, it underperformed.
Now, when you look at the 180 mg, same dose, but given on a Q12 week basis, the 180 mg outperformed the 120. So a nice dose response there. The hypothesis is, our working hypothesis is small sample size. So there's only seven patients in that cohort, and each patient accounts for about 18 percentage points. And there were two patients in that cohort that had no response. Yet they had tryptase that was completely floored. So it's telling us that we're getting rid of those mast cells, but those two patients had no response. More than likely, those two patients don't have CSU. In CSU, it's a diagnosis by exclusion. There's the possibility that other diseases manifest and look similar to urticaria but aren't mast cell-driven. That's the hypothesis. That's what's happened in those patients.
Those patients are still blinded, so we can't do the definitive diagnosis, which is to do a biopsy, which once those patients are unblinded, we'll see if we can get their consent to do that.
Got it. Got it. The next topic that I would like to touch on is the safety. Which you alluded to a little bit earlier, I guess what's your latest views on the safety profiles of briquilimab and maybe the broad anti-c-Kit antibody? I know you've reported early data on the safeties, I mean, particularly with respect to the hair color change, the taste change, and neutropenia. I mean, what do you think about the long-term treatment paradigm with the anti-c-Kit class and briquilimab?
Sure. Again, there's those five cell types in the body that present c-Kit. As a class, I think we now have a pretty good picture of what's the effect of dosing and hitting those cell types. The great news is that to date, there have not been any surprise AEs with our drug or with barzolvolimab. It's well understood what's happening. I think early on, there was a concern about neutropenia. You're blocking stem cells, so are you going to really set off an impact, a cascade in the hematopoiesis? What we now know is that when you block c-Kit on a stem cell, you don't deplete that stem cell. The stem cells become a little quiescent while they're trying to figure out an alternative survival mechanism to stay alive.
It's important to note also, and because we've worked in the transplant space, that only about 10% of the bone marrow, 20% are actively needed to maintain normal hematopoiesis. If you're blocking that, the other cells upregulate and you get back to normal hematopoiesis. Having said that, the significant difference between our drug and barzo, their half-life is about 21 or 22 days. Ours is about nine days. The way that they're dosing, either every four weeks or every eight weeks, they constantly have drug on board. If you look at their neutrophil counts, they go down and then they stay down as long as the patients are on drug, where with briquilimab, the neutrophils dip slightly, but then they come back up right correlating to the half-life of the drug.
The hypothesis here and from the early data is that we may be able to reduce the number of c-Kit adverse events, the severity of those events, and maybe even eliminate those. We will see when we have longer-term follow-up, but I think the safety profile is looking really good that this could be a chronic therapy without significant adverse events.
Got it. Thank you. Thank you, Ron. I mean, obviously, we'll see more with the longer-term follow-up data, which is basically the next area that I would like to discuss. Obviously, you plan to provide an update from the BEACON study in mid-2025, or to be precise, the first half of the third quarter, right? You were being very specific. Just maybe give us an overview in terms of what you're going to show. I know there are a few different cohorts and how many patients of data that you plan to show.
Sure. I think these next cohorts of data that are coming in the mid-year will be really important data to enable us and you and the investors to really understand the differentiation between briquilimab and barzo. Importantly, for Jasper and briquilimab, it will really enable us to choose the doses to move forward into our phase ii- B adaptive clinical trial that we intend to initiate before the end of the year. Specifically, data that will be coming in that timeframe. First, slightly before then, we also have announced that the patients in the inducible urticaria trial, the SPOTLIGHT trial, those patients, 12 patients that are dosed at the 180 mg dose level, that data has been accepted for presentation at EAACI. That will be in the middle of June. The SPOTLIGHT data at the 180 will be presented there.
Then specifically to the BEACON data, there are a number of cohorts of data that will be coming. There will be four additional patients at the 240 single dose level. There will be eight total patients to look at for the 240 as a single dose. There will be eight patients at 360 single dose, thinking that that potentially could be a loading dose. The drug was fairly safe at 240, so we wanted to push it up to 360. The important cohorts I think that people are really waiting for are the 240 Q8 week and the 240 followed by 180 Q8 week. Each of those cohorts will have eight patients in those cohorts.
In addition to that, all the patients that have been on the BEACON study for at least 24 weeks are eligible now to roll over into the open label extension, which is 180 mg Q8 weeks. We would anticipate having somewhere in the neighborhood of 20 or 25 patients' worth of data at that time. I think that that will also go a long way to resolve that question about from January, the 180 Q8 week. Now we'll have 20 or 25 patients to add to those seven patients.
Got it. Got it. Very helpful. Just in terms of expectations, benchmarking on the efficacy and safety, what do you have the bar, internal bar on that front, 100% CR for 240?
Yeah, I don't think 100% will continue. I've been doing this now for almost 40 years, and I've yet to work on a drug where it works on 100% of the patients. Having said that, yes, if our objective here is to really come out of the BEACON study with two doses, we can move into our phase II- B study that really will give us the opportunity to show that differentiation and optimal biologic dosing. We know that we have doses that can drive complete responses and have durability. We know we have safety. We didn't really touch on this before, but in the safety, there were only 15 total c-Kit-related adverse events in the first 12 weeks of the BEACON study. All of those c-Kit-related adverse events, except for one, were all grade one, so mild, transient, and importantly, self-resolved before the next dose.
We didn't have a single patient who had to have a dose alteration, discontinuation, drug holiday. Every one of those patients that had those c-Kit-related adverse events went on to their next dose right on time, including the one patient that had a grade three neutropenia. That patient, we found out afterwards, had a history of idiopathic neutropenia. Importantly, that patient has now gone on to two additional doses of briquilimab without a repeat of that grade three neutropenia. That's really comforting for us to see that that safety profile was consistent in that type of a patient. If we're able to show that the c-Kit-related adverse events with briquilimab in a larger sample size really are mild and transient, that will be significantly different than anything else out there.
From an efficacy standpoint, if we can match the efficacy that has been seen with barzo, then that's a home run to have a differentiated safety profile and a similar safety or a similar efficacy. Yeah, we'd be very happy with those outcomes.
Barzo is the bar.
Yeah.
Got it. Obviously, you're going to pick two doses. Are they going to be from this cohort? I mean, which more or less every eight weeks? My question is, would you consider a lower dose, for example, at 120 for once every four weeks to move forward with that?
I think we have enough data to suggest that that could be an option. However, I think we have enough data also that would tell us that we don't have to do a four-week. The drug at eight weeks, whether that's the 180 or the 240, is safe at that level. From a convenience standpoint for the patients and a tolerability, that will more than likely move forward with two eight-week doses. We'll let the data tell us what's the best thing to do.
Got it. Got it. Obviously, you plan to start, I think you have data for phase II, II, III, I think, with those two dose cohorts in the second half of 2026, and then pick one to move forward with phase III. I guess, how do you see the positionings in terms of the timeline relative to bazro? Barzo has already got their phase III started with more doses in their studies. How do you see the timeline relative to barzo?
If we are able to achieve those timelines that you just described, that puts us about 18 months behind barzo.
Got it. Okay. Got it. Very helpful. What's your thought about the broader CSU, I mean, urticaria landscape? DUPIXENT just got approved, and remibrutinib is going to have the, I think, NDA submitted soon. That's also an emergence of oral c-Kit inhibitors. I mean, maybe could you help putting briquilimab in context with obviously the small therapeutics good for the patients, but it's also, I think, intensify perhaps the competitive landscape.
Sure. First, we're very pleased that DUPIXENT got approval. From our standpoint, that will only help to teach derms how to use a biologic in CSU, which they currently don't have an option for something like that. In fact, a lot of these patients are referred out from the dermatologists. I think in an oversimplification and maybe being overly reductive, there are only two drugs out there, either in development or approved, that deplete mast cells. That's briquilimab and barzolvolimab. All of the other therapies out there only inhibit the mast cell. They don't deplete the mast cell. You see that in the efficacy difference when you look at whether it's remi or Dupi or oma. They have nice efficacy, but it doesn't come close to what's been observed to date with briquilimab and barzolvolimab because we're depleting the mast cell.
Good news for CSU patients that currently have omalizumab and antihistamines. In the future, they'll have treatment options, but we think that briquilimab has the opportunity to be the therapy of choice in this disease setting.
Got it. I know we're almost out of time. Maybe just in the last minute, could you maybe tell us more about the broader pipeline? I know we expect another data point later in the second half from the asthma study, and then potentially there could be a fourth indication. How do you prioritize that?
Again, sort of how I started the conversation, we think diseases that are mast cell mediated, mast cell driven are prime targets for us to go after. We chose asthma. Asthma is our next indication outside of the urticarias. We're looking at mild and moderate asthma. Those data will be available in the second half of this year. We're really encouraged about the opportunity in asthma. There are upwards to 20-30 other diseases that we're looking at.
Got it. Awesome. I think we are at time. Thank you so much, Ron, for joining Alpha Thai Chat.
Thank you.