All right, well, good morning, everyone, and thank you for joining us at Needham & Company's 23rd Annual Healthcare Conference. My name's Ethan Markowski, and I'm a biotech associate here at Needham. With us today is Ronald Martell, CEO of Jasper Therapeutics. I will let him give an overview of the company and recent developments, and then we'll save some time for Q&A at the end, so I'll pass the floor over to you.
Thank you, Ethan. As Ethan stated, I'm Ronald Martell. I'm the CEO of Jasper Therapeutics, and on behalf of all of my colleagues here at Jasper, I'd like to thank Ethan and Gil and Needham for the opportunity to discuss Jasper Therapeutics with you this morning. As a reminder, certain statements I may make today may constitute forward-looking statements. I refer you to our Form 10-K and 10-Q, currently on file with the SEC, and any form of 8-Ks that may have been filed subsequent to those filings. Jasper Therapeutics, we are focused primarily on our lead compound, an antibody that has franchise potential in mast cell diseases. c-Kit is the target.
It's a validated target that we know that we have the ability to drug and that drugging that target, the clinical relevance of drugging that target is becoming much better understood, specifically on mast cells. Mast cells are key drivers of immunologic and dermatologic diseases with high unmet medical need, and briquilimab is a potent c-KIT inhibitor. And what we now know is that we have to deplete those mast cells, and it's a rare opportunity in any disease when you have the ability to safely deplete the perpetrating cell. And briquilimab has all of the ideal properties that you'd like to have when using specifically an antibody to target a cell like a mast cell, given its shorter half-life, and its potency to bind with a higher affinity and avidity than the normal ligand.
Our 2024 will be a transformational year, where we're focusing on two significant clinical trials, one, the Beacon study in CSU, or chronic spontaneous urticaria, and the Spotlight study in inducible urticarias. In addition to that, we've noted that we will initiate yet another clinical trial this year in a yet-to-be-named mast cell-driven disease. We continue to expand our portfolio, beyond what the company was formed around in the stem cell transplant conditioning space. We have a couple of ongoing clinical trials there that continue to generate interesting data like Fanconi anemia, sickle cell. In addition to that, the most mature program is the severe combined immunodeficiency, or SCID, where we believe we've enrolled enough patients that could form the backbone of a BLA, and we have ongoing conversations with the agency around the possibility of filing a BLA in that SCID population.
But for 2024, our primary focus is on the mast cell side of the business, in CSU and CIndU. So as I stated, mast cells are the key drivers of these of a number of different diseases, and specifically, diseases that are in the skin, the lung, and the gut. And when activated, so when SCF, or stem cell factor, binds to c-KIT on the surface of a mast cell, it powers the mast cell. It is the life source for the mast cell, and it enables it then, when it's triggered to degranulate and cause diseases like CSU and CIndU, as well as other diseases. And unfortunately, the current therapies that are approved, like omalizumab or antihistamines, don't do anything to inhibit or to deplete the mast cell. They're mostly focused on downstream activity, once the mast cell is triggered.
However, with briquilimab, we bind to the binding pocket of SCF with a higher affinity or avidity than what SCF does, and thereby we shut down all signaling to the cell. And what's now known is that when you block all signaling, via SCF as a primary survival pathway for the mast cell, that you then the cell upregulates BIM, which activates apoptosis, an organized cell death for the mast cell. And if you inhibit and block SCF from binding to c-Kit to a significant threshold to initiate that apoptosis, that apoptosis happens within hours. And within days or weeks, the mast cells are depleted from the skin. So it's an important driver for the survival, of these mast cells. And we know that with our antibody, it's a humanized aglycosylated IgG1 antibody, that it's important that the antibody be aglycosylated or have a null Fc.
It's important to understand about the design of the antibody that that's the only modification that has been made to the antibody. It's a single amino acid substitution at N297, a glutamine for an asparagine. The making minimal alterations to the glycosylation pattern of the mAb or of the antibody is really important to help avoid or eliminate ADAs or antidrug antibodies. To date, we've only seen about 15% of the patients develop ADAs, and to date, none of those antibodies have affected the PK or the PD of the antibody. Also, with briquilimab, in the design of the antibody, it only has a half-life of about nine days. We think that's really important and relevant in a disease like CSU or CIndU.
Given that, the antibody acts within hours to initiate the BIM-mediated apoptosis, then if the mast cells are gone within days or weeks, we also know that mast cells take many weeks or months to return, maybe 18-20 weeks to return. So providing an opportunity for patients to have a significant drug-free interval, we think, will be advantageous for the patients moving forward. So as I stated, we know that by blocking c-KIT on the surface of a mast cell into a significant threshold, that apoptosis happens within hours, leading to mast cell depletion. Here are results from our Healthy Volunteer study. In this study, we evaluated four doses in this population. 48 milligrams, 84 milligrams, 158, and 280 milligrams. What you'll see here is that at the lowest dose, most of the patients did not have mast cell depletion. One did.
It was a lighter weight patient, that probably approached more of the threshold of concentration to initiate mast cell depletion. But what you'll notice is at the 84 milligram level, so that most of those patients, in fact, had significant or greater than 60% of their mast cells in their skin that was depleted. And these results are looking at day 29, so a very nice dose response curve here for depletion of mast cells. So we believe with briquilimab that somewhere around that 0.8 or 80 milligram to 1 milligram is the dose where we will begin to see significant mast cell depletion. And along the X-axis here in the blue bubbles are the doses we'll be evaluating in our Beacon study, and the orange bubbles are what we'll be evaluating in the Spotlight study.
So we think that the important thing here with briquilimab in these diseases is to follow optimum biologic dosing. And so what do I mean by that? Well, we'll be looking if we know that there's a threshold of concentration to deplete the mast cell, so what's the ideal dose to deplete the mast cell, and then what's the interval of time, and don't dose again until the mast cells start to return. To date, we've studied briquilimab in more than 150 patients and healthy volunteers. And the safety profile here looks very relevant and important, and optimal for dosing diseases like CSU and CIndU and potentially other mast cell-driven diseases.
In addition to the patients we treated in the healthy volunteers, we've conducted a number of non-human primates, most significantly a 26-week chronic dosing, weekly dosing with doses as high as 300 milligrams per kilogram in these primates on a weekly basis. And what we observed in that was that, specifically on the hematopoietic lineages, such as the neutrophils and the red blood cells, that we did see about an 8%-12% decrease from baseline. However, what we did not observe, and we've now seen this in the human population as well, is that with subsequent doses, we did not see any additional increase, or decrease rather, in the reticulocytes or in the neutrophils. And so, it's really important to know that we don't have a continued impact on the stem cells in the bone marrow.
In addition to that, all of the effects on these other c-Kit presenting cells, like the melanocytes and the spermatogonia, all resolved with cessation of therapy. So as I stated, it's important to think about dosing these patients from an optimum biologic dosing standpoint. If we're initiating apoptosis in these cells and the mast cells are all gone within days or weeks, as you'll see in a study here from barzolvolimab, in their CIndU study with a dose of 3 milligrams per kilogram, a single dose, what you observe is that same phenomenon. You see this rapid depletion of the mast cells in the skin. And what you'll also notice here on the left panel is that not till probably week 18, maybe week 20 or 24, do the mast cells even start to think about returning.
So if you've depleted the mast cells and they're all gone from the skin in a matter of days or weeks, we think that this is where we have a significant advantage to, with the shorter half-life, and our dose and schedule, to give the patient as much of a drug-free interval as possible. That's because c-Kit is presented on a number of other cells in the body beyond, mast cells, stem cells, Cajal cells, the GI, melanocytes, taste buds, spermatogonia. And if the biggest sink of c-Kit in the body, is the mast cells in the skin, and if those cells are all gone, then free circulating antibody, there will just be more antibody, to target those other c-Kit presenting cells. So we believe that with a longer drug-free interval, we could have a better overall safety profile for these patients.
So let's take a look at the Beacon study, our first study in chronic spontaneous urticaria. It's a randomized double-blind, placebo-controlled, ascending dose study. We will be enrolling patients who have had CSU for greater than six months, have mild to moderate CSU, as evaluated by the UAS-7 score of greater than or equal to 16. These will be adult patients. And all of these patients will be of the highest unmet medical need. And by that, I mean they will have all failed H1 antihistamines and will have had an inadequate response to omalizumab. This is the patient population that has the highest unmet medical need.
It should be important to note that if we are successful in this study and move forward with our registrational program, which if we're successful here, we would have planned to initiate in the second half of 2025, we would in that study, we would enroll all-comers, so patients that have failed antihistamines and patients who are omalizumab naive or have had an inadequate response to omalizumab. We're conducting this study in the U.S. and the EU at approximately 30 sites. The lead investigators in the U.S. are Tom Casale, and in the EU is Dr. Marcus Maurer. We'll be enrolling about 38 patients in this study. In this study, the primary endpoint will be the UAS-7 score at 12 weeks. And in addition to that, we'll be looking at correlations between serum tryptase and skin biopsies.
This study, again, is designed as an ascending dose study with multiple cohorts. After reviewing and designing this study with both KOLs and the FDA, our objectives in this study were to design a study that really could interrogate optimal biologic dosing and, if we're successful, enable us to move from this study to our registrational study. It's important to note that this study is conducted with our sub-Q formulation, the same formulation that was used in the healthy volunteer study that I presented a moment ago. And in addition to that, this past year, we conducted and have already completed our three validation drug product and drug substance lots. So the product that will be used in this clinical trial and any clinical trial moving forward will be our commercial-grade drug.
We've significantly de-risked the CMC portion of the program with briquilimab and would believe that, we have essentially our module three for the BLA, related to briquilimab on the shelf. Let's turn now to the conduct of the study. Part one of the study is looking at doses of 10 milligrams and 40 milligrams. Again, I'll refer back to the Healthy Volunteer study, where we would expect that these would be subtherapeutic doses. These will be really interesting questions for us and to help us begin to address Project Optimus, as it will be difficult if we're successful moving forward to ask patients who, in the future, to go back and, be dosed at the subtherapeutic levels. In the part two, the randomized, double-blind, placebo-controlled portion of the study, we'll be looking at multiple dose levels here as well as dose intervals.
So the first dose level is at 80 milligrams. Well, we will be dosing these patients every eight weeks. We think that eight weeks is likely the shortest interval that we would need to dose with briquilimab. Then we'll move up to the 120 milligram dose, and you'll see there's two cohorts here at Q8 week and Q12 week, and then to 180 at a Q12 week. The final cohort here is a single dose of 240 milligrams, where we're interested in understanding, if you use a very significant dose like 240 milligrams, do you get deeper depletion of the mast cell? And if there are deeper depletion, does that correlate to any lengthening of return of the mast cell? So you might think of the 240 milligram for future development, as a loading or induction type of a dose.
What we've guided to is that we will have the initial data from this clinical study in Q3 of this year. And specifically, when we say the initial data, it's the first 4 cohorts: the 10 milligram, the 40 milligram, 80 milligram at Q8, and 120 at Q8. And when we bring those data forward, likely not at a scientific forum given the timing in Q3, but more likely in a company-announced and sponsored event to review the data, it will be on the UAS-7 at 12 weeks on those first 4 cohorts, as well as all of the corresponding data on serum tryptase and skin biopsies. Throughout the course of this year, then in the second half, we'll bring forward the remaining data on the 120, the 180, and the 240.
If we stay on the schedule that we believe we're on now, more than likely, the full study design would be available for AAAAI in February of 2025. Our second study that we're conducting in this space is the so-called SPOTLIGHT study in CIndU, inducible urticaria, where we're enrolling two types of urticaria: symptomatic dermographism and cold urticaria. In this patient population, all of these patients will have had the disease for at least three months. They all will have failed antihistamines and be all adults or greater than 18. We're conducting this study only in the EU, at five sites, and the lead investigator is, again, Marcus Maurer. So it's a pretty straightforward study, studying two dose levels, again that 40 mg, probably at the subtherapeutic level and the 120 mg level.
In this study, these patients will be given a provocation test, either the FricTest or the TempTest, which you'll see in the pictures on the right. They'll be administered a single dose of briquilimab, and then they'll come back 12 weeks later and will be given that same test again, the FricTest or the TempTest, and will be scored on their responses at that time. So, when we present the data on this study, sometime in the second half of this year, we'll have that 12-week score along with serum tryptase, skin biopsies, and other safety and other markers on all of these patients as well. Moving now to the opportunity, a very large market opportunity in the urticarias.
When you look at the data that's been generated to date by third parties here, you'll see that CSU and CIndU in the G6 represent a very large market opportunity, with about 1.4 million patients that have moderate to severe disease and about 150,000 patients that are treated annually with Xolair or omalizumab. Having said that, it takes a significant amount of time for OMA to have an effect, and probably upwards to 40% of those patients to have an inadequate response to omalizumab. Looking at the development in this space, we think that c-Kit depletion or mast cell depletion, rather, sits at the highest level in the order of hierarchy of design of therapies. And currently, there are only two that are in development: our antibody and Celldex's barzolvolimab.
All of the other therapies, the IgE or OMA, the IL-4/13, Dupi, Novartis's BTK, all of these strategies are inhibitory, so they do not deplete the mast cell. With an inhibition strategy, like any of these other drugs, you need to maintain constant inhibition of the mast cell, or the symptoms will come right back. Novartis, at their college meeting when they announced their top-line data, anecdotally mentioned that patients who stopped taking remibrutinib even for a day or two, their symptoms came right back in a day or two. And we've seen that with other therapies as well, that you need to maintain that constant inhibition, or the signal will come right back. So we think the best way to approach mast cell diseases are to deplete the mast cell.
So lastly, on this portion, just to review for a moment, so briquilimab is a monoclonal antibody targeting c-Kit. It's an aglycosylated IgG1 humanized antibody, with a short half-life of only about 9 days. Barzolvolimab has a half-life of about 21 or 22 days. And their dose and schedule, every 4 weeks or every 8 weeks, means that with barzolvolimab, they will constantly have drug on board. So we think that by depleting the mast cells and with a shorter half-life and a longer interval of dosing, that we have an opportunity to have not only a dose and schedule that is convenient for the patients, where maybe they're only receiving drug once a quarter or potentially even longer, but also a longer drug-free interval. Lastly, I stated that we're interested in exploring additional indications with briquilimab in mast cell-driven diseases.
There are probably 20 or 30 different diseases that we've taken a look at. In the bottom left here are a handful of some of the ones that are pretty interesting, like allergy or anaphylaxis, asthma, atopic derm. What we've demonstrated here at AAAAI this year, we had 3 sets of data that we presented to 1 oral and 2 posters, demonstrating the Jasper mouse. What is the Jasper mouse? In a normal mouse, a human antibody will not bind to the extracellular domain of c-KIT. So we've engineered a proprietary mouse where we've knocked in the human external domain of c-KIT. So now, for the first time ever, we can test directly in animal models, briquilimab.
We think that we have a significant strategic advantage here and look forward to presenting additional data on the power of this molecule over the course of this year. Turning now to one other study that we're conducting, looking at utilizing briquilimab as a single agent in low-risk MDS patients. In these patients, they have mainly a diseased bone marrow. They still have a few healthy stem cells in their bone marrow. And the hypothesis is here, by using briquilimab, we can mobilize or deplete those diseased stem cells, keeping the healthy stem cells and not depleting those, and making more room in the bone marrow niche so that the healthy stem cells can repopulate. It's probably important to stop it at this point and revisit a little bit about c-Kit on stem cells.
What's known about stem cells are that, unlike mast cells, stem cells have redundant survival pathways. So just blocking c-Kit on the surface of a healthy stem cell does not deplete those stem cells. If you block them for long enough, they will move down a platelet lineage and may move out of the bone marrow. But in order to get direct cell killing, as we've observed in our other transplant studies, you need to combine c-Kit with low-dose radiation or azacitidine or something like that. And what we also know here, because we have worked directly in the bone marrow, is that we're able to maintain those healthy stem cells.
This study will be an interesting study to evaluate and understand if we're able to make room in the bone marrow niche by keeping the healthy stem cells in the bone marrow niche and mobilize or move the diseased stem cells out. Like I said in the beginning, looking at our portfolio, we have a number of ongoing clinical trials here in the stem cell transplant space. Having said that, most of those studies are being conducted by either academics and institutions or by the NIH. The company's focus for 2024 and moving forward into 2025 will be on the mast cell side of the business. With that, in Q3 this year, we anticipate bringing forward the initial data on CSU.
Immediately on the heels will be the data from the CIndU study, and we'll have a number of conferences that will be presenting data at this year. Our cash runway extends through Q3 of 2025. So 2024 will be a very transformational year for us, and we look forward to presenting data, demonstrating that briquilimab is a potent antibody with the ability to deplete mast cells in mast cell-driven diseases. Great. Thank you for the presentation, Ronald. At this point, we'll move to the Q&A portion. So feel free to put your questions in the chat, and maybe I'll go ahead and get us started. You mentioned earlier in the presentation about the importance of ADAs and you know that briquilimab caused a relatively low rate. Can you put that into comparison to barzolvolimab? Because I know that's one question we hear investors mention quite frequently.
So do you know what their rate is? And maybe just touch one more time on why there might be a difference there.
Yeah. Thank you, Ethan. So yeah. So again, we've observed about a 15% ADA rate. And and that's with both our sub-Q and our IV. To date, the only thing we know about Barzo is in 2023, at an AAAAI poster with their IV formulation, they stated that they've observed 51% ADAs, no comment on neutralizing or impact on PK or PD. And that was with their IV formulation. Typically, you see a bit more ADAs with the sub-Q formulation. I I think mechanistically, and it's why I touched on the single amino acid alteration for briquilimab at N297, is that we know that with Barzo, they've made six different structural modifications to their antibody, both to nullify the FC and to increase the half-life.
Typically, the more changes you make to an antibody and the glycosylation pattern, the higher probability the body will see it as foreign and will make ADAs. So we think and the antibody community understands this. So we think that there's a possibility for higher ADAs with barzolvolimab. And as a single point of data, it appears that way. It's not yet understood the clinical relevance of that yet. Great. Thank you. And follow-up question. So I know you touched on it again in the presentation, but can you just talk a little bit about how much of an advantage the Jasper's proprietary mouse model gives you for moving into additional indications? Because that was one part that kind of stood out to me that makes Jasper a little unique compared to some of the other companies in the space. Yes.
We think it is a very significant strategic advantage, as evidenced by the data we generated and presented at AAAAI this year, looking at mast cell involvement in airways. Previously, nobody has the ability to do that in an animal model. And now we can do that for any of the diseases we want to look at. We're able to then generate an animal model to enhance our probability of success should we move into the clinic in any of those diseases. And one of the things we take great pride in here at Jasper is really understanding the biology of a disease. And I think you see that from the Jasper mouse as well as our biologic approach to dosing in the Beacon study. Great. And maybe moving on to LRMDS.
You know, recently, there was an advisory committee meeting for Geron, and wondering if you had any takeaways from that meeting or any lessons that you could apply for future development there. Sure. Well, I think, you know, it first and foremost, it's great for patients with low to intermediate risk MDS. So we're very happy for the community to have another treatment option. I think it was also reassuring to see the agency approve. Well, I guess the AdCom did. But I think the agency will likely follow that the support for those endpoints in the study, so impacting the hematologic indexes and making patients transfusion independent is a viable endpoint for approval.
I think significantly, as it relates to briquilimab, that if we're able to modify the disease directly in the bone marrow, that this could be a transformational approach to treating these diseases.
Great. And with that, I think we are running close to time. So I just want to thank you again for attending our conference and for telling everyone a little bit about Jasper Therapeutics.
Great. Thank you, Ethan.
Thank you. Take care.