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, our President and CEO. Welcome, Ron, and just like you to give a brief introduction, and a description of the company for those who are not familiar with the story.
Great. Well, Pete, first on behalf of all of my colleagues at Jasper, we'd like to thank you and Cantor for this opportunity, and for all of your market-leading support and your coverage of the company. We really appreciate it. Thank you. So Jasper Therapeutics, we are a clinical stage biopharmaceutical company. Our lead program, briquilimab, is a monoclonal antibody targeting c-Kit, and we're specifically focusing on c-Kit in mast cell-related diseases. We have ongoing clinical trials in CSU, or chronic spontaneous urticaria, and CIndU, inducible urticarias, and we're looking for significant data readouts in Q4 from those trials this year.
Yeah, so like you mentioned, briquilimab is your lead candidate. You know, and it's being developed in several indications. You know, just a little bit background on briquilimab, and you know, what are some differences with other c-Kit monoclonals?
Sure. So briquilimab is a humanized IgG1, a glycosylated antibody. It's really important that in treating mast cell diseases, that you have an antibody that has a null Fc. Novartis taught the field this a number of years ago, and we have a well-designed antibody. In fact, our antibody was originally designed and developed by Amgen, and so we are the beneficiaries of their knowledge and expertise here. To nullify that Fc, we've made only a single modification to the structure at N 297 , an asparagine to a glutamine. So it's really important that you don't fix complement, you don't activate ADCC around an antibody or around a mast cell, but it's also important that you do that with minimal structural changes to the antibody.
It's known in the field, the more structural changes you make to an antibody, the higher probability you will have of ADAs. And to date, that seems to be playing itself out well. With our subQ formulation, we've observed about 14% ADAs, and those to date, those ADAs have not affected the PK/ PD of the drug. So we really like the structure and the design of the antibody. And the other thing that Amgen did, which is very classic in antibody design, is they designed briquilimab to bind to the epitope where the natural ligand stem cell factor, SCF, binds. And as you would expect, we have an antibody that binds with a higher affinity or avidity than the natural ligand.
Excellent. So I remember being out at San Francisco in wintertime as we entered the new year, 2023. I remember entering the meeting with you, and then basically you had just announced that you reprioritized sort of your pipeline. And so just asking you, you know, do you still view that as the right decision? And you know, I do. You can look at the stock price and so.
Stock price aside, but that's always the one of the big weighing measures, right? If you made the right decision, and that certainly tells us that we made the right decision. We were in a very fortunate place, though, where you know the company had conducted six different clinical trials in the transplant conditioning space, and demonstrated that not only is it very safe to use an antibody when targeting stem cells, and we can talk more about the safety profile of the drug. We generated really good data there, and continue to in disease settings like SCID and Fanconi anemia.
Having said that, the upside opportunity that is in mast cell diseases, and as you said, at that time, we announced we were going into CSU and then CIndU, and then this year now we announced that we're initiating a clinical trial this year in asthma. And so the opportunity in mast cell diseases is just such a large opportunity that can't be denied.
So you do have two studies underway, for briquilimab, the BEACON study, CSU, and, SPOTLIGHT study, you know, which is, chronic inducible urticaria. You know, you do have data expected later on this year. Just, starting with the BEACON study, you know, just describe the design and, the data that, you had in hand that helped, guide that design.
Sure. So the BEACON study, or the so-called BEACON study, it's our 1b, 2a clinical trial in CSU. So this study is very similar to the study that Celldex ran in that it's enrolling moderate to severe CSU patients, so patients who have a UAS7 of 16 or greater. So these patients have all failed antihistamines. And one of the differences between our study and the study that Celldex conducted is we're in this study only enrolling patients who had an inadequate response to omalizumab or Xolair. And so the study is classically designed, as you might expect. We're looking at a number of different dose levels and dose intervals.
And I think this is a significant departure from what Celldex did, where you know, it's a classic drug development cadence of you know, every four weeks or every eight weeks, with a doubling of the dose, and where we're following the biology of the mast cell. So it's known that c-Kit is the primary survival pathway for mast cells. If you shut down c-Kit, you shut down phosphorylation, and importantly, you shut down FOXO3a. FOXO3a is responsible for regulating Bim, and when Bim is unregulated, it will initiate apoptosis, and this happens irreversibly within hours. But in order to do that, you have to reach a concentration of saturation of the c-Kit receptors on the surface of a mast cell to initiate that apoptosis.
I think what you were alluding to was a healthy volunteer study that was conducted in 77 subjects, and in that, there were four dose levels: 42 milligrams, 84, 158, and 280. What was observed was at the 42 milligram level, only one of the subjects had any mast cell depletion. So it was telling you at that level, and for a wide range of body weights, only one of the subjects reached enough saturation. But when we moved to the 84 milligram level, all but two of the subjects had at least 60% of their mast cell depletion. So that told us that somewhere around 80 milligrams is that threshold of concentration with briquilimab.
We designed our BEACON studies to really starting with a therapeutic dose of 80, and then moving to 120, then 180, and then ultimately, 240. So we're looking at a range of dose levels and dose intervals at 8 weeks and at 12 weeks, to look more at the biology of the timing of the return of the mast cell.
Right. And when it comes to that data, you know, there was a certain time point where they actually looked to evaluate the mast cell in the skin. So, you know, is there. You know, we've spoken in the past, and basically, you know, you sort of mentioned that perhaps the mast cells haven't been cleared out. And so in terms of apoptotic mast cells still in the skin, you know, what are your thoughts around that?
It's certainly. So again, we know that if you reach a threshold of concentration, you will push the cells into this irreversible apoptosis. Having said that, it does take a while for phagocytosis to remove the mast cells from the skin. And so if you look at some of the mast cell depletion data, you'll see this rapid depletion. But for the skin to really reach the nadir of the mast cells, may take, like, six or seven weeks. And part of that is due to the technology and immunohistochemistry. Immunohistochemistry, it's good for looking at the presence of mast cells, but it really can't tell you whether the mast cell is alive or dead.
But what it also can do is tell you when the mast cells start to return, because then if you reach a nadir, and then you start to see an inflection in the mast cells, then you know that that's only coming from new mast cells that are growing.
Okay. And you know, originally, you know, in the early part of 2023, you sort of laid out the plan of what we expect to see when. And you know, part of the plan was to see some data. I believe two cohorts in 3Q. But you recently changed those plans.
Correct.
And so what drove that, and what should we expect to see when?
Sure. So when we gave guidance at another conference in January, we had only enrolled one patient, and so we really didn't know how long it would take to enroll the study. And if we looked at the analog from Celldex, it told us that it may take us up to 18 months to enroll the study. And so we thought that that was probably too long for a company like Jasper to wait for data. So we set an internal goal and objective for the first four cohorts, the 10 milligram, the 40, the 80 at Q8 week, and the 120 at Q8 week in Q3.
What substantially changed was that, in the late second quarter, the enrollment really started to pick up, and so we ended up well ahead of our enrollment projections, and so investors don't like it when you give partial data, and as a drug developer, you don't like to look at partial data sets either, so it made absolute sense for us to move out the guidance from Q3 to Q4, but be able to tell everyone that we would be able to provide all of the patients in all of the original planned cohorts in Q4.
Okay. And, you know, in terms of the data to come in Q4, you know, what should we sort of expect to see in terms of time points? You know, are we gonna see one- and 12-week, or are we gonna see multiple data points, you know, within that timeframe?
So, certainly on all patients, we will see the 12-week UAS7, and the 12-week UCT. We'll also have tryptase on all of those patients. What is still to be determined, and it depends on, you know, how fast we can clean the data and how clean we can get the data, is there will be patients that have been enrolled longer that we may be able to provide more of a time course, and a look on all those patients. And we'll see as the next month or two go by here how much of that data we'll be able to get cleaned. And I also should point out, we'll of course have the safety data on all these patients as well.
Okay. And now, expectations in terms of, you know, base case, to actually move forward, you know, what would you like to see?
If we have data from one of the cohorts, the efficacy data that's comparable to Celldex, that's a clear win. It means we have a drug, and we're off and running. I think from there, if we're able to dose at intervals that are longer than Celldex, then that means we might have a drug that's more convenient for patients. And then lastly, and of course, you know, this is the big one, but I don't know, you know, how we'll be able to see if we'll be able to see that in this study, given our half-life, our half-life is about nine days, theirs is about 21 or 22 days, and if we have a longer dosing interval with a shorter half-life, that could translate into a better safety profile.
Mast cells are the largest sink of c-Kit in the body, and if we're depleting all of them or substantially depleting them, then if you're dosing to more of an AUC type of a dose schedule, then you're just going to have more free antibody on board to hit those other c-Kit presenting cells that could lead to a difference in adverse events.
You know, these are small sample sizes, so what is your expectation in terms of variability? How are you gonna handle that if you have?
Yeah, well, you're absolutely right. I mean, the total sample size is less than 50 patients. It is placebo-controlled. Although, to be clear, the placebo control is really not for statistical analysis, it's for study conduct. We felt it really important to make certain that both patients and physicians were blinded in this study, especially given that the UAS7 is a patient-reported outcome. We felt it's really important to have that placebo control. Specifically to your question about, you know, small numbers, you know, we'll have to wait and see what the data tell us here.
But we're certainly expecting that, you know, we have an active drug and that one of these dosing cohorts will be able to find that it's at a minimum comparable to Celldex.
You know, one question I'm sure you get constantly, and I've had multiple times. And you alluded to it, and you did sort of answer it, but I'm gonna ask it again. Is basically, are you gonna be able to thread the needle when it comes to safety and efficacy? And basically, specifically neutropenia and on the HSC.
Yeah. I actually think that, and we've felt this for a long time because of our history working in the bone marrow, that I don't really think, and I think that the field is starting to come around to this, that there's really a threading the needle on the heme safety. So we know, and we presented some data at EMBRN this year, and we'll have some data coming later this year from our low-risk MDS study, where giving briquilimab and then looking directly in the bone marrow in this low-risk MDS study, where we took bone marrow biopsies from these patients, and where we can observe that briquilimab doesn't have a deleterious effect on healthy stem cells.
So healthy stem cells, arguably the most important cell in the body, have redundant survival pathways, and just blocking c-Kit does not make them, apoptosis does not kill them. And it makes them maybe become a little more quiescent for a little while, or if you block them long enough, it may move them down a platelet lineage, but you're not going to create chronic neutropenia in these patients. And so, one thing I think we do agree with Celldex on here is that, you know, there will be a first dose impact on the stem cells.
And we think that that impact is probably somewhere in a 10%-20% drop in the neutrophils. Having said that, if you look at the inclusion or exclusion criteria from the BEACON study, our ANC threshold is 2,000. So even if you have a 20% drop in neutrophils from 2,000, that's a lab value, but it doesn't result in an AE. And so, again, I think that there's some ways that, you know, we can manage this so that, you know, move beyond the perception to the reality that it doesn't appear as if we're having long-term deleterious effects on healthy stem cells.
Okay. You know, and part of the part three, I guess, of the study, you have one single high dose, 240 milligrams. Just help us understand the rationale for evaluating that, and then, you know, sort of tie it into Celldex's approach. You know, are you actually thinking about having some type of loading dose?
Yeah, so we, that's exactly why, you know, a year or so ago, when we designed this study, we were already thinking about the possibility of a loading dose. Again, the biology that we described earlier, where reaching a threshold of concentration to initiate the apoptosis, that, you know, a loading dose, an induction type of a dose to deplete as many mast cells as you can on the front end, is probably a good idea. And so that's why we added the final cohort at the 240 level, and why it's only a single dose, because we wanted to see, is there any differential in the depth of depletion? And then, does the depth of depletion have any correlation to the return of symptoms, or does it change the return kinetics from...
for the mast cell and the mast cell timing that they may return? If you only deplete 60%, do they return sooner? Or if you deplete 100%, do they stay depleted longer? We just don't know the answer to that, but we wanted that answer. Because whether it's for a disease like CSU or CIndU, or going into, like we are, a disease now like asthma, where asthma may be a good example of where you'd want that loading dose. You wanna drive them down as fast as possible, and then maybe convert to a maintenance dose. This study will teach us a lot about mast cells and about briquilimab that may extend beyond the CSU study.
If you had to speculate why they put a loading dose?
You know, I would--
If you look at their previous data.
Yeah, I think that, you know, there's no difference between their 150 Q4 and their 300 Q8. And so, you know, if they're trying to bump up that efficacy, that would imply the only way that they may be able to bump up the efficacy is by hitting the mast cells harder up front. There's also could be the speculation that, you know, it's driven by ADAs as well. Avoiding the impact of ADAs by driving the mast cells down as quick as possible. Either way, I think the concept is a smart one.
And now, when can we actually expect to see the complete data set?
So if we remain on the trajectory that we are now, we would expect that likely Quad AI in February of next year is when we would have, of course, not the 52-week data, obviously, but the top line complete data set from the study.
Right. Let's move on to CIndU. You do have the SPOTLIGHT study ongoing. Just to discuss, you know, basically, the study design, you know, the endpoint, and, you know, what would you consider a win in terms of efficacy?
Sure. So the SPOTLIGHT study is in inducible urticarias, and we're enrolling two types of inducible urticarias in this study. One is symptomatic dermographism, excuse me, and the second is cold urticaria. These amount to about 70% or so of the inducible urticarias. Study is really a straightforward study. The patients present. They receive what's called a provocation test, according to their disease, a cold test or a friction test, which is a scratch test. They receive that test, and they receive a dose of briquilimab. We follow them weekly for 12 weeks and look to see if there's a resolution of their disease. Study is designed with a single dose of briquilimab. We're testing 40 milligrams in that study.
Again, we don't expect the 40 to be efficacious, but it's an opportunity for us and the regulatory agencies recognize that if we're successful in the BEACON or SPOTLIGHT study, it'll be difficult to ever go back and ask patients to receive one of these sub-therapeutic doses. But it would be important for us to understand those dosing levels, and then the therapeutic dose level is at the 120 milligram.
Okay. Now, a win for you?
A win is, you know, if we again have data that looks comparable to Celldex, and it means, you know, we are the definition of a fast follower. They're only 12-ish months ahead of us.
Right. And, you know, when you think about the market, you know, in terms of CSU and urticaria in general, how are you sort of viewing that? And, you know, I guess you're sort of positioning yourself, you know, after Xolair, why not go second line?
Yeah, so I actually don't think of us as the second line to Xolair. We'll certainly be second line to antihistamines. Antihistamines will always be a first-line therapy. To be clear, in the BEACON study, we enrolled only patients who had an experience with omalizumab. And we did that really because we thought it would help with enrollment. These patients have the highest unmet medical need. They don't have any other options, and it looks as if that played itself out in the way the enrollment's gone. In our registrational studies, we'll take all comers, Oma naive and OMA experienced.
And, you know, in thinking forward about the market, first, I'd say it's really good for CSU patients that there are a number of drugs that are in development. You know, this market looks something like the psoriasis market did, eight or so years ago, when people were questioning just how big of a market is it? You know, how bad do patients need these drugs, and would derms prescribe a biologic? And now, you know, there's more than eight drugs that do couple of billion dollars each, in that market, and I think the CSU market could be very much like that, that there are so many patients who just don't get seen because there aren't treatment options. And, to be overly reductive, but, indulge me for a minute.
You know, the only two drugs out there that have shown that they can deplete mast cells are our drug and barzo. While there's a lot of other drugs in development, if you can have a drug like ours, where maybe every eight weeks or every 12 weeks, you see your derm or immunologist for a 2 ml sub- Q, and you go away and forget about your disease, you don't have to worry about it for another 8 or 12 weeks, because the mast cells are gone. This is one of those settings where taking an injection more frequently, like OMA or taking an oral once or twice a day for the rest of your life, where the those scenarios may aren't really a competitive advantage.
Right. How do you view small molecule, you know, in terms of c-Kit versus monoclonals, you know? You know, can you actually achieve that efficacy?
Yeah, I think, you know, the one of the key pieces you just said there is about inhibition. So, you know, all of those, all the small molecules, whether it's c-Kit specific or, you know, BTK, they only inhibit the mast cell. And so, you know, if you don't take the drug, and if you don't maintain 24/7 , 365 inhibition, the mast cell's right there to go back in business, and you'll have your symptoms right back immediately. I think that, you know, the challenge with the small molecules will still continue to be: How can you achieve high enough concentrations to inhibit the mast cell, but maintain a clean safety profile?
We have about two minutes left, you know. Would love to go into some of the other programs like asthma, ask you some questions, but perhaps we'll reserve that for another fireside chat in a couple of weeks or something, you know? So basically, you know, if we're sitting here, you know, 12 months from now, and I ask you, you know, what are the key value-creating events that you've had in the past year? You know, what would you like to say?
Positive data from the BEACON study, positive data from the SPOTLIGHT study. 12 months from now, we'd hopefully have positive data in hand from our asthma study. We'd have FPI in our registrational clinical trial in CSU and potentially registrational trial in CIndU. So there's a lot of execution and a lot of significant milestones over the next 12 months.
Excellent. Ron, thank you very much for attending our conference and doing the fireside chat. Always great to see you.
Thank you, Pete.