Healthcare Conference. My name is Greg Renza, one of the biotechnology equity research analysts here at RBC. For the next session, we're pleased to have Jasper Therapeutics. Joining us from Jasper is the Chief Executive Officer, Ron Martell. Ron, it's good to see you, and thanks for being here.
Greg, thank you. On behalf of all of my colleagues at Jasper, really appreciate you and RBC providing us this opportunity this afternoon.
Great. Great. So yeah, for those who may not be aware of Jasper, very interesting story, and just want to ask you, Ron, to give a brief introduction to the company or just outline the thinking on c-Kit as a therapeutic target and the stage and the trials that you're working on.
Sure. So Jasper Therapeutics is formed around our lead program, a monoclonal antibody called briquilimab, previously known as JSP-191. This is a humanized IgG1 aglycosylated antibody targeting c-Kit on the surface of mast cells. The company has been in development for the last few years, using this antibody in seven other clinical trials. And last year, we announced that we would be moving into mast cell diseases, specifically chronic spontaneous urticaria and CIndU or inducible urticarias. And those two clinical trials are underway. And a data readout from those trials here in the second half of this year, third quarter for the BEACON study, so-called BEACON study or the CSU study.
So 2024 will be a very transformational year for us as we bring that data forward. We added to that earlier this week, and you were part of helping us break that story of announcing that we would be pursuing yet another mast cell driven disease in asthma. We intend to begin enrollment of that study before the end of the year.
That's great. So certainly adding asthma to the mix in addition to CSU and CIndU, so some rather attractive large I & I indications. And maybe with respect to chronic urticaria, just talk a bit, Ron, about c-Kit's role as a therapeutic target. Just broadly, but maybe weave in a little bit just the comparisons to maybe other targets that are in development, but also that may be currently available that in the current treatment paradigm. We'll go from there.
Sure. So c-Kit is a receptor on the surface of mast cells. And mast cells are, let's call them the perpetrating cell in a number of diseases, including the urticarias and asthma and others we can talk about. And c-Kit has been known to be the primary survival pathway for mast cells for a number of years, decades, in fact. However, it's been a very difficult target to drug, especially with small molecules. c-Kit is prevalent on other cells in the body: stem cells, spermatogonia, Cajal cells of the GI, melanocytes, taste buds. And so, the difficulty with small molecules are how do you drug c-Kit without having all of those other on-target c-Kit effects?
It's one of the great things about an antibody is you can have an E to T of one. So you know what that receptor is, and if you can design an antibody to specifically bind to that target, then your probability of clinical success goes up. And we're very encouraged by you know, the design of our antibody and really understanding the biology of mast cell-driven diseases, and specifically, we'll talk about the urticarias or that. Again, c-Kit is a primary survival pathway. If you shut down that pathway, then you stop the mast cell from degranulating or releasing the particles that create the itching, the hives, the wheals in these diseases, or in asthma, you know, the asthma that you see, right?
So, by shutting that pathway down and making those cells apoptosis, you actually make the perpetrating cell leave, and those cells leave the body. This is a rare opportunity in medicine where we know what the perpetrating cell is and where it appears as if we can safely deplete that cell. So, I think as one key opinion leader told me at a Quad AI meeting earlier this year, that mast cells are having their moment. And it's great to be living in that moment.
Maybe, Ron, just walk us through some of the supporting preclinical data, the clinical data that you're pointing to, to indicate briquilimab's efficacy in CSU and also in CIndU.
Sure. Well, it certainly in drug development, it starts with the preclinical. And someone taught me a long time ago in drug development, there are three major boxes you need to check in drug development. The first is, is the target validated? Check. This target has been known for a couple of decades. The second box is, have you validated you can drug that target? Check. We've treated more than 150 patients to date, including 77 healthy volunteers, where we look specifically at the mast cells in their skin. I'll come back to that in a minute. But the third box, and the most important box is, has the clinical relevance of drugging that target been validated? And the answer is yes.
There's a growing body of data that absolutely support the validation that if you deplete a mast cell, that translates into a clinical outcome and a meaningful clinical outcome. You know, in drug development, it's often you know, like Schrödinger's cat, right? When you run that clinical trial for the first time, you're not really sure if that biology will translate into human biology. And now, having us and others in this field have conducted a number of clinical trials that validating deleting the mast cell is will lead to meaningful clinical outcomes.
And on the healthy volunteer study, just remind us what was observed in terms of that mast cell depletion, those recovery kinetics, and even some of the relevant biomarkers that are suggestive.
Sure. So again, the mast cells are, are in the skin. They're also in the alimentary tract and the lung and the gut, and, in females, in the uterus. And but the vast majority of mast cells are in your skin, and that's what causes these, these diseases, like, like urticaria. And so, we conducted a healthy volunteer study, to look to see if we can actually deplete the mast cells in the skin. And in 77, volunteers that participated, we looked at four different dose levels, and what we observed in that study was a very nice dose-response curve in the four different dose levels. But importantly, we saw significant depletion of the mast cell in the skin.
So what we did was we took a 2-mm biopsy before the drug, gave them the drug, waited two weeks, did another biopsy, waited two weeks, and did another biopsy. Same exact size of biopsy and in proximity to the previous biopsy, so it's the same skin. And what we saw was exactly what the biology would tell us, is that these cells apoptosis irreversibly, rapidly, within hours of exposure to the drug, and within a couple of weeks, these mast cells are apoptosis, and then phagocytosis removes them from the skin. And so at four-week period of time, we saw a significant amount of depletion of the mast cells in the skin. And why this is important is, you know, I keep talking about mast cells.
Well, in diseases like CSU and CIndU, and even asthma, the mast cell is actually not a diseased cell. I mean, we, we think a lot in oncology terms, where, you know, the cell is diseased. There's something aberrant about that cell. Well, in diseases like CSU and CIndU, the cell is actually not diseased. There's something else in the immune system or autoimmune that is triggering that mast cell. And so by taking biopsies, actually from healthy volunteers, those are the same mast cells that somebody that has CSU has, though.
Mm-hmm. And do we have a sense of what level of mast cell depletion is needed to drive the clinical activity in chronic urticaria?
We don't have great data on that yet.
Mm-hmm.
Celldex has certainly presented some early data from one of their studies where they showed significant depletion. But there hasn't been data yet that correlates the depth of depletion to response. That's one of the things we will be looking at in our BEACON study and SPOTLIGHT studies. The other important thing, though, that the Celldex data taught us is that mast cells take a really long time to recover. So once you deplete the mast cells in the skin, they take 18, 20, 24 weeks to return to the skin. So, importantly, when we think about our drug development program, if we depleted mast cells in a matter of the first couple of weeks, they don't return until 18-20 weeks.
Mm-hmm.
Then we certainly don't want to have drug on board, exposing patients to a drug that potentially could give adverse events or hit other c-Kit-presenting cells. And so that's taught us a lot about our drug and about the disease. And so we're approaching our dosing in these studies from an optimum biologic standpoint, to really just focus on the biology of the mast cell and drug the mast cell, not the patient in general.
Yeah, that's great, and certainly with the relatively shorter half-life, this can kind of enhance the safety and tolerability. What have you observed so far? What would we see as potential levels of acceptable, call them AEs or safety findings? Of course, we're thinking of the neutropenia, the hair color alterations, even the taste and the dysgeusia.
Right. So neutropenia is something that has been a primary concern from the introduction of drugs that target c-Kit, because c-Kit is present on stem cells, arguably the most important cell in our body. And so you having a drug that does not deplete stem cells is really important. We know a lot about the stem cells, though, we know that again, they're high level of importance to the body. They have redundant survival pathways, so just blocking c-Kit is not enough to kill the stem cells. But what's that translate into from a neutropenia standpoint? What we've observed in our studies, and I think Celldex's data are similar, is that with an initial dose of briquilimab, we see about a 10% drop in neutrophils.
However, what we don't see, and we've looked at this in both the healthy volunteers as well as a chronic tox study, we did a 26-week chronic tox study, that we didn't see any additional reduction in neutrophils with subsequent doses. So that's really important. And if you start with a normal neutrophil count, and again, ostensibly these patients have CSU or CIndU, not a disease of their bone marrow. So if you start with an ANC of 2,000, a 10% drop in your neutrophils will be imperceptible. And so we're cautiously optimistic that you know there won't be a requirement for any monitoring moving forward, and we won't have a significant deleterious effect on the bone marrow of these patients.
Okay, great, great. Just looking forward to the plans or to the coming data, what can we anticipate from the CSU study? You mentioned the Beacon trial in the third quarter. How many patients is part of the plan? What are the dose levels?
So, it's again, important to step back for a minute and to understand a little bit about the trial design. So again, we designed this study in concert and collaboration with our advisors and key opinion leaders, as well as the regulatory agencies. We thought it was really important to design a study that really test two hypotheses. One is, what is the dose of briquilimab that drives mast cells into apoptosis and then drives the level of depletion that corresponds to a significant or the most significant level of efficacy? And then the second question is, so when do we bring the drug back on board based on the timing of the mast cells? If you were to look at the design of our study and the number of cohorts, that explains that design.
So with that in mind, what we've guided is that in Q3 of this year, we'll have the first four data cohorts that we'll report out. And most specifically in those data cohorts are a data cohort at 80 mg given every eight weeks, and then another one, 120 mg, given every eight weeks. And so those are the first doses we think that cross that threshold of concentration to initiate the apoptosis. And then subsequent to that, a little later in the year, we'll bring forward two more cohorts, 120 mg at Q12 weeks and 180 mg also at Q12.
Again, we'll be looking at different dose levels to drive depletion and then different intervals of time of bringing the drug back on board for when the mast cells may start to return.
Great. Then on SPOTLIGHT in CIndU, just speak about that potential to translating the dosing and frequency of from the CSU trial to the CIndU approach.
Sure. So, in CIndU, or inducible urticarias, or our so-called SPOTLIGHT study, we're studying two types of CIndU, symptomatic dermographism, or SD, and cold urticaria. They make up about 70% of the inducible urticarias. The cold urticaria is one that can be fatal. Some people, if they jump into a cold lake or walk into a walk-in freezer or something like that, actually could, could die from this. So, there's a significant unmet medical need here. In this patient population, we'll be looking at primarily another dose of 120 mg in these patients. So it gives you an idea of where we think, you know, our therapeutic dose might be, around that 120 mg-180 mg range.
Those patients will come into the study, they'll receive a standard provocation test based on the type of urticaria they have, receive a dose of briquilimab, wait 12 weeks, the patient will come back and receive the same provocation test. So, the strong read-through, either from CSU to CIndU or CIndU to CSU, is it's the mast cell. If you're able to deplete the mast cell and deplete it durably, then you should have significant efficacy.
You mentioned Celldex's Barzo. How do you articulate briquilimab's positioning amongst the competition, amongst Barzo, and which data sets can offer more visibility to you and the team onto the potential for a superior efficacy profile or superior profile overall?
Yeah. So first of all, we're fans of Barzo. We, you know, this is a unique opportunity to be a fast follower. They've certainly taught us and the field a lot with the data they've generated, and it enabled us to be smarter, well, more informed in the designs of our clinical programs. And you probably see that read through from their data as an example, that they're the ones that have generated the data, showing that mast cells likely don't come back till, like, week 18 or week 20. So we thank them for that. Having said that, you know, there are some significant differences in the antibody. You touched on one of them earlier, the half-life. Ours is about 9 days, theirs is about 21 days or 22 days.
So if you're trying to give patients as long of a drug-free interval, having a shorter half-life here is certainly an advantage, we believe.
Great. Great. And then, what distinctions do you draw when it comes to c-Kit targeting between monoclonal? You touched on the antibody approach, but that versus small molecules, which modality, when you look forward, do you think it has the prospect of achieving the best clinical adoption?
Well, again, I think, it's, mast cells are having their moment. There are a number of drugs that are in development in this space. At the risk of being overly reductive, our antibody, and Celldex, the antibody approach is the only approach that is depleting the mast cells. All of the other drugs that are in development are inhibiting the mast cell. So they're focusing on one of the receptors on the surface of the mast cell, and attempting to block that signal so, the mast cell can't be triggered and degranulate. And the challenge with the small molecule is that a couplefold. One is ensuring that that is the trigger, right?
So let's say in the case of, you know, X 2, as an example, one of the hot targets, you know, how do you know that that urticaria is actually triggered by X 2? What if it's triggered by something else? Is that, as a drug that's inhibiting X 2, going to work in all patients? I think we've learned a lot about that from Xolair, as an example. So, omalizumab, you know, it works on the IgE pathway, and so it probably explains why Xolair doesn't work in some of the patients, that it doesn't work is because their urticaria is probably not IgE triggered. So, as a drug developer and an advocate for patients, I hope somebody can unravel the Gordian Knot for some of these small molecules.
But I think it's going to be an ongoing challenge to get an IC 50 or some level where you're getting enough inhibition or otherwise to dampen the signal, but have a safety profile, and yet also not have to take, you know, 700 tablets a year if it's a BID oral, and remember that compliance, so.
Great, and maybe we'll just circle back to the most recent news, just on asthma as a third indication. A KOL event coming up on May 20th, I believe. What can we expect from that? What should we be looking forward to learn? And maybe just comment a bit, Ron, just on the rationale for pursuing asthma and how briquilimab is the right choice for that.
Sure. So we've been working on selecting our next indication for the better part of a year-
Mm-hmm.
Really interrogating the biology of the mast cell and of these other diseases. And what really pushed it over the line for us in picking asthma is the availability of clinical data. And again, going back to box number three, is there data that validate the clinical relevance of drugging this target? And in fact, in asthma, there is. There's two studies that have been conducted with a drug you all may know of, Gleevec, and one of which is authored by Dr. Josh Boyce, who will be the KOL on our call on Monday, that shows that, you know, you—if you drug c-Kit on a mast cell in asthma, it, it, you can have a clinical outcome, but it's a really toxic drug, and so the toxicity profile isn't acceptable.
So we've looked at all of that data, and there's other clinical data sets, another one with a drug called masitinib, that really reinforced to us that the mast cell is the conductor in the orchestra here. And if we can safely remove that, then good things will happen.
Good. Well, maybe we'll leave it there, Ron. Look forward to next week and the KOL event, and congrats on the progress to date, and looking forward to the data coming later this year. Thank you.
Thank you for having us, and thank you for your support.