Good morning and welcome to the Jefferies Global Healthcare Conference. My name is Matthew Bacora with the Jefferies Healthcare Investment Banking team, and it's with my great pleasure to introduce you to Ronald Martell, the CEO of Jasper Therapeutics.
Thank you, Matthew. On behalf of all of my colleagues at Jasper, we want to say thank you and really appreciate Jefferies for providing us this opportunity. Safe harbor statement, as you all have heard before, I encourage you to look at our filings with the SEC here, as some of the statements I may make today may constitute forward-looking statements. Jasper Therapeutics, our lead program, briquilimab, really is the definition of a portfolio and a product and has true franchise potential in mast cell mediated, mast cell driven diseases. We know that the mast cell is the perpetrating cell in a number of diseases, maybe better than 30 diseases. We are currently studying a couple of those in a couple of urticarias and in asthma. Importantly, the mast cell is a normal healthy cell in these diseases. The mast cell is not pathogenic.
However, it is the perpetrating cell. What's really important to note about the mast cell is a receptor on the surface of the mast cell called KIT, a tyrosine kinase receptor, that this receptor acts as the sole survival pathway for mast cells. When the normal ligand stem cell factor binds to KIT, it activates the survival pathways and energizes the mast cell. When we block KIT with our antibody, we shut down all downstream signaling. When you shut down downstream signaling, you shut down FOXO3A, and FOXO3A is responsible for regulating BIM. When BIM is unregulated, it tells the cells to die. That really relates itself then to, or lends itself to, using an antibody as a therapeutic here to target mast cells and leads to a very superior efficacy profile and a very favorable safety profile.
Continuing with that biology of a mast cell, we know, again, if you drug them, they will die. It takes a while for the mast cells to return to the skin. We think that the right way to treat mast cell related diseases is get the antibody on board, initiate that apoptosis, clear the antibody out, and then bring the antibody back before symptoms return. Ideally, we could do this with a lot of diseases where you give patients drug-free intervals and you really only have the drug on board when that perpetrating cell is set to cause the problem that's associated with the disease. That is what we're doing here with briquilimab. As I said, we're currently in three clinical trials, mast cell clinical trials, chronic spontaneous urticaria, chronic inducible urticaria, and asthma.
I'll talk specifically about each one of these as I move forward. Chronic spontaneous urticaria is quite a debilitating disease. Some think that it's just hives. You can tell from these pictures that these are not just ordinary hives. This has a very significant impact on the quality of life of these patients. We're currently conducting a study we refer to as BEACON. It's our phase one to study in chronic spontaneous urticaria, where we're looking at a number of different dose levels as well as dose intervals. Again, we're looking at all of these different doses and intervals because we think that the ideal way to drug this is from an optimum biologic dosing standpoint.
This will give us that data to be able to identify what is that right dose up front, what's the right interval for that dose then to bring the drug back, and is it the same dose level or maybe it's a reduced dose level. In January of this year, we presented the data from the cohorts listed here in blue. In the cohorts in orange, our data that will be coming mid-year. We recently provided some updated guidance on what does mid-year mean. Mid-year means we will have this data in the first half of Q3 this year. What we've learned so far about briquilimab in urticarias and specifically in chronic spontaneous urticaria is that briquilimab demonstrated a rapid onset of clinical activity. This is really important for those patients.
If you remember back to that picture, if you have that type of hives that are completely covering your back or your entire trunk, you do not want to wait four or six weeks for a drug to work. You want this drug to work now. In a moment, you will see from the efficacy where we saw significant clinical responses within the first week, deep and durable clinical responses here, and a safety profile that certainly looks favorable. What we have learned additionally here is we will start with the PK, very nice dose response to the PK. With Cmax's here and the Tmax that almost looks more like an IV, you can see within days, each of these dose levels reaches its Cmax. Again, we believe that the apoptosis for the mast cells are Cmax driven.
Also, I'll point out that our half-life is only about nine days. When you think about the half-life in nine days and typical antibodies with drug clearance, three, three and a half half-lives, it means that we're below those therapeutic thresholds probably by week four-ish or so. Why is that important? I'll get to that when we talk about safety. Continuing with the data driven from the BEACON study here, we're looking at the tryptase levels corresponding to dose. Mast cells produce tryptase. It's a signal that they send out. Mast cells produce probably about 99.5% of the tryptase in the body. Basophils produce a little bit, but it's predominantly the mast cells that are producing tryptase. It is an absolute correlate to mast cell presence, inhibition, and depletion.
What you'll see here is starting in the light blue at the 80 mg dose and then 120, 180, and 240. Again, a very nice dose response here. At all levels, we did see patients have their tryptase go below LLOQ. At the 180 mg and 240, we saw the most sustained reduction in tryptase. That would imply that we're seeing mast cell depletion here, not just mast cell inhibition. Again, going back to that half-life, if you're thinking of maybe about four weeks or so is when you're starting to lose that concentration necessary for depleting mast cells. If you're looking at the orange line at the 240, you'll see that that suppression of tryptase is maintained for another four weeks. That's likely coming from the fact that we depleted a significant amount of these mast cells.
One of the primary endpoints of the study and a validated efficacy measure is a score called the UAS7. What you'll notice here is a couple of things. One is our nearest competitor, barzolvolimab, is in yellow. These are the data from their clinical trial. I recognize this is a cross trial comparison, but I will thank Matt Phipps for putting this slide together. He's given us the ability to use this slide. What you'll notice here is in the 120 mg, the blue line, and the 240 in the orange line, within the first week, patients had a significant drop in their UAS7.
At the 120 mg dose, if we would have dosed this as a four-week drug instead of an eight-week drug, what you see there is that the efficacy maximizes in the two to four-week range, but then we start to lose that efficacy because of the shorter half-life of the drug. By week eight, when we give the second dose, it is almost back to baseline. This time you will notice that it drops all the way down to zero and the patients experience a complete response. Now, turning to the 240, what you will see here is again that very rapid response. In fact, by week two, all three patients in this cohort experienced a complete response. That was durable through an eight-week period of time. We are very pleased by the overall efficacy we have seen here.
Here's sort of putting it into perspective of the other drugs that are either approved or in development. omalizumab or Xolair is approved in CSU. Dupixent is now approved here as well. In development is or seeking approval is remibrutinib and then rarzolvolimab in the yellow and then briquilimab in the orange. You'll see that our efficacy stands up nicely to any of the drugs that are approved or in development in CSU. Here's just another way of looking at the 240 mg dose cohort. We're also looking at well-controlled disease. That first chart didn't show you when we were looking at that spaghetti plot, it showed the loss of complete response starting at week eight. What was incomplete there was showing that some patients still, one of the patients still had a complete response out to 10 weeks.
Two of the patients had well-controlled disease out to 12 weeks. Turning now to safety, I stated that we had a favorable safety profile. This is the overall safety analysis and treatment emergent adverse events. You'll see that we did have 27 of those compared to eight in the placebo arm. We did have one treatment-related serious adverse event. We had one patient experience hypersensitivity to briquilimab, not an anaphylaxis, but a hypersensitivity. Now let's turn to the specific KIT-related adverse events. This is all tied back to the optimal biologic dose. Why do we want to give patients as long of a drug-free interval or reduced exposure is because there are other cell types in the body that present KIT, mainly melanocytes, taste buds, cells in the bone marrow, and the progenitors of the spermatogonia.
It is really important if we want to reduce the incidence of these and potentially the severity of these KIT-related adverse events that we do not constantly block those cells. We think that we have the ability to reduce the incidence as well as the severity of these events by dosing in an optimal biologic dosing standpoint. What you will notice here is the melanocytes associated with hair color changes. We observed four patients that observed hair color change compared to one in the placebo group. In the taste change, we had six that had hypogeusia. This is actually a loss of a certain type of taste. The taste that is associated here is in the umami, bitter, salt that patients may notice that they have an absence of that. This is not like paxlovid where you are walking around with a constant metallic taste in your mouth.
It's an absence of taste. I think importantly here is that the median time for resolution here was 31 days. This was very transient and self-resolved. In fact, all of the CTCAE adverse events that were observed with briquilimab all self-resolved before the next dose, which is really important. Patients did not have to make the choice of coming off of the drug. There were no drug holidays, dose delays that were required. Turning lastly to neutropenia, it's called neutropenia as an adverse event, but really what we're talking about here is a reduction in neutrophils. We're not talking about patients developing any clinical sequelae. This is not febrile neutropenia. This is a transient drop in neutrophils. We did see one grade 3 neutropenia, again, without any clinical sequelae. It just met the criteria of grade 3 by the total number of neutrophils that it went down.
Importantly to note that this patient had a history or has a history of idiopathic neutropenia and thrombocytopenia. Importantly, this patient was on the 180 mg Q8 week dosing cohort. This patient has gone on to multiple additional doses of briquilimab and has not experienced another grade 3 neutropenia. How does this compare to barzolvolimab? You'll see that at their 16-week time point, their data looked somewhat similar to ours at the 30-week time point. Having said that, they have not disclosed their taste change since their first IV study. We're not sure exactly how it compares. I think one of the big things here is the difference between what happened with their 16-week data and 52-week data. Again, this is where we think we will have a significant differential profile is they're drugging the patients in an AUC.
They're maintaining constant inhibition of the mast cells and then by extension, all these other KIT presenting cells. Especially on the melanocytes, which affects the hair color and the skin hypopigmentation, we think that that's why that shows up over time. If in fact we're giving the melanocytes time off to recover, restore the production of melanin, we may be able to reduce the incidence and severity of these two adverse events. One last thing on safety, looking at the neutrophils, what you'll see here is the neutrophil counts by cohort. I'll draw your attention to the orange line, the 240, so the highest dose that we've reported on to date. What you'll see is that there is absolutely this KIT class effect. On first dose, you see a depression in the neutrophils.
What we see here with briquilimab is that by week four, the neutrophils start to recover. This is in keeping with exactly what we're attempting to do here. If we think about the neutrophils as a biomarker for the melanocytes or the taste buds, we think that we may be able to restore function in those cells before we give the next dose to, again, potentially have a significantly differentiated safety profile. I mentioned the data that will be coming in the mid-year that were the cohorts that were listed in orange. Those are the data that are in the center of this slide where it says additional data coming in 2025. What I didn't mention was two pieces of this information.
One is that next week at the EAACI meeting next Saturday, we will be presenting data from our SPOTLIGHT study or the study in inducible urticaria. We will be reporting out data on the next 12 patients in that study that were at the 180 mg dose level. In addition to that, later when we have the mid-year data, we will have data from the open label extension portion of the BEACON and SPOTLIGHT studies where all the patients in that study are then eligible for this open label. We would anticipate in the mid-year to have 20-25 patients who have had multiple doses of 180 mg in the CSU study and probably 10-15 patients from the SINDU study.
All of this will enable us to then select our dose to be used in our phase II-B clinical trial that we're planning on commencing in the second half of this year. It will lead then to our phase III registrational program approximately one year later. I mentioned the SPOTLIGHT study. This is the study that will read out at the EAACI meeting enrolling two types of inducible urticarias, cold urticaria and symptomatic dermographism. We will report on the patients with the 180 mg dose level. We saw very nice efficacy from single dose at 120 mg here where 93% of the patients had a clinical benefit in this study. 92% of the patients at 120 mg had either a complete or partial response.
The 180 milligram dose level was durable, as you'll see here from this time frame here for the better part of four to six weeks. We'll be looking to see if the 180 milligram level extends the durability beyond the six weeks that was observed with 120. Safety profile consistent with what we previously showed, although no hypersensitivity reaction. We've only seen the one in the BEACON study to date. Let's turn now to asthma. We are very interested in this study as well. It is well known that mast cells are sort of the conductor in the orchestra. They get the whole party started for an asthmatic response. They're responsible for releasing everything from prostaglandin to R2 to initiate the asthmatic response. We are attempting to see if we can knock down those mast cells in the lung. Can we affect that asthmatic response?
We'll also be looking secondarily. Mast cells are known to be involved in the recruitment phase, including recruiting such things like eosinophils. Currently, the endotypes in asthma are driven by eosinophils. It will be very interesting to see if we can knock down the eosinophils here as well. This clinical trial is an asthma challenge study where we identify what allergen, cat, dander, house mites, tree pollen that a patient might be allergic to. We challenge them and we give them briquilimab. We bring them back for a challenge six weeks later and then 12 weeks. We'll measure their FEV1. We've guided that these data will be available in the second half of this year. Very large market opportunities here.
There are a number of other drugs that are in development on the left-hand side of the page with two of those drugs being approved in Dupixent and Xolair. Having said that, there are only two drugs that are depleting mast cells, and that's briquilimab and barzolvolimab. All of the other approaches are only inhibiting the mast cell, and we believe that the superior approach will be to deplete the mast cells. Very large market opportunity in urticaria, more than 3.5 million patients in the G6 with a significant number of these patients that are uncontrolled by antihistamines. Asthma, very large market opportunity as well. Ultimately, we think that this franchise, again, really the definition of a portfolio and a product, it could be significant here in the tens of millions of patients in all of these areas.
In conclusion, 2025 is going to be a very important and transformative year for Jasper with the mid-year readout and the initiation of our phase II- B adaptive clinical trial that will run directly into our registrational trials next year, the readout coming up in a week on the [SINDU] brackets study and then the asthma study in the second half of this year. Thank you very much.