All right, good afternoon, everybody, and thank you once again for joining us for the 45th Annual TD Cowen Healthcare Conference. I'm Yaron Werber from the biotech team, and it's a real great pleasure to introduce Ron Martell, CEO of Jasper. I think Ron and I have known each other for 23 years or 24 years. It's pretty crazy going back to a long, long time ago. Ron's going to do a presentation, and then we'll open it up for Q&A as well. Ron, thanks for coming. We appreciate it.
On behalf of all my colleagues at Jasper, I'd like to thank Yaron, Jana, and the TD Cowen team for this opportunity this afternoon, and look forward to discussing Jasper Therapeutics. As I discuss Jasper this afternoon, I remind you all that some of the comments I make may constitute forward-looking statements and direct you to our Form 10-K, Form 10-Q, and others that outline some of those risk factors, and those are all available on our website. Briquilimab. Briquilimab is Jasper's lead asset. Briquilimab is an antibody-targeting c-Kit, and I'll talk a little bit more about the biology here as we move forward, but there really is an opportunity for franchise potential here with Briquilimab in mast cells.
Mast cells are known to be the primary driver of multiple allergic and atopic diseases, including urticarias and asthma, but two diseases where we have ongoing clinical trials and other interesting opportunities like food allergy or potentially COPD. This afternoon, I'll discuss primarily our BEACON study in CSU, highlight just quickly our study, a SPOTLIGHT Study in CIndU, and then our upcoming data in asthma in our so-called adhesion study, and those data will be available in the second half of this year. The building blocks are being put into place for this franchise potential and an opportunity to really have a differentiated compound in this space in the diseases like urticaria, but more broadly as it relates to mast cells. It really does start with the biology of the mast cell. C-Kit is the primary survival pathway on a mast cell.
If you stop stem cell factor or SCF from binding to c-Kit or CD117 on the surface of a mast cell, you shut down all downstream signaling. All phosphorylation shuts down, and importantly, you shut down FOXO3A. FOXO3A is responsible for regulating BIM. When BIM is unregulated, it initiates apoptosis. This all happens within hours, but this is the critical piece, is that shutting down c-Kit makes mast cells apoptose and leave the skin, and they're the perpetrating cell in the diseases like urticarias. We have a specific antibody that is designed to target c-Kit. It binds in the epitope, same epitope, it's sort of 1, 3, where the normal ligand does, binds with a higher affinity and avidity, and importantly, only has about a nine-day half-life. Why is that important?
We think the underlying thesis here to really have a differentiated compound and approach to these diseases is to dose the initial dose to deplete those mast cells, lean into the half-life to clear the drug out. C-Kit is present on a number of other cells in the body, like taste buds, melanocytes, stem cells, and briquilimab will target those other cells, but we lean into our half-life so that the briquilimab is only on those other affected cells as little as it needs to be or as little as it needs to be in order to deplete the mast cells.
We're approaching this from an optimum biologic standpoint, and we're now beginning to see from the data that are emerging from BEACON and from SPOTLIGHT, the ability to have that, the properties of the antibody and this approach lead to a differentiated profile as we approach these diseases. Let's talk about urticarias. Urticarias are a debilitating inflammatory disease. This is not just merely having a few hives or itches. As you see, unfortunately, you see some of these pictures here. This is a chronic condition that unfortunately also leads to an increase in suicide. These are significant hives, wheals, and itching that these patients live with. Unfortunately, there's only two approved therapies in this space. One is antihistamines, and most of these patients are on four times the FDA-approved dose.
In fact, I just came from AAAAI, and there were a number of posters there written about the so-called fog that these patients live in because they're taking such high levels of antihistamines. We think we have an opportunity to really give these patients not only a better quality of life, but a quality of life that comes on with a rapid onset of the drug. I'll show you those data in a moment. The data I'll speak to here come from our study called the BEACON study, the study of briquilimab in chronic spontaneous urticaria, randomized, double-blind, placebo-controlled study, where we looked at a variety of doses and dose intervals to really interrogate that optimal biologic dose strategy. In this patient population, we enrolled moderate to severe, so patients that have a UAS7 of 16 or greater.
Those pictures that you observed, that's those type of patients we're talking about. All of these patients had to have failed antihistamines, and all the patients in the blue cohorts that you're looking at here all had to have failed the only other approved drug, omalizumab or Xolair. This is a highly refractory patient population that didn't have any other options that enrolled in this clinical trial. Approximately 30 sites in the U.S. and EU. Dr. Tom Casale is the U.S. primary investigator, and on Saturday, the BEACON study was selected this past Saturday at AAAAI. The BEACON study was selected as the late breaker in this section, and Dr. Casale presented the data.
In the evening on Saturday, Dr. Martin Metz, the other investigator, he leads the EU, did an event for us, and those data, or that presentation rather, is available on our website. I would encourage you all to go and listen to Dr. Metz's presentation on the BEACON data as well. Primary endpoint here, UAS7, and of course, we looked at important biomarkers like tryptase, and I'll show you those data in a moment.
As I stated, the data we reported earlier and that were presented at AAAAI or the cohorts in blue, I'll be walking you through some of that data. In addition to that, we have a number of additional cohorts that are currently enrolling in the study, and those data will read out in the mid-year timeframe, and I'll talk a bit more about the timing associated with those. What do we find in the BEACON study?
What we saw is what we had hoped we would see, and based on the biology of the disease and the design of the molecule, we're starting to see that differential profile play out. What we observed were rapid onset of clinical activity. Within one week of administration of briquilimab, patients started to see a benefit, and within two weeks, patients were having complete responses. Those pictures you just saw, patients that looked just like that, within two weeks, 100% of their hives, wheals, and itches were completely gone. Not just a reduction, but patients were seeing complete resolution of their disease within a two-week period of time. In addition to that, overall, on the UAS7 score, we saw as much as a 29% or a 29-point drop in the UAS7. Again, if you remember, all these patients had to have at least 16 or greater.
That makes them mild or moderate. You see if they had a 29-point score coming in or they had a 29-point drop, that means that they had to have had a score above a 30 or so, a 35. We saw these responses be highly durable, and depending on the dose, at the 120 mg dose, the complete response was durable for about a four-week period of time, at the 180 mg, about six weeks, and at the 240 mg for about eight weeks. With a single dose of briquilimab, you saw complete responses, and you saw dose-dependent durability of those complete responses as well. Importantly, in this patient population, safety and tolerability is really important here as well. With the exception of my note about suicide, you know, this isn't a fatal disease.
It is important to have a favorable safety profile, and again, we're seeing that differentiated safety profile from both the approved therapies and the other drugs that are in development. We're seeing that safety profile play out in that the safety, the AEs associated with briquilimab were mild, transient, self-resolved before the next dose. What do we observe? First of all, from a PK, we saw a very nice dose-dependent PK, and I'll draw your attention here really to the Tmax. Not only do we get a significant Cmax here, but what you'll see here is we have a Tmax that looks almost like an IV type of a drug. This drug rapidly leaves the subQ, gets into all five compartments, and then ultimately, from the next slide, you'll see that it rapidly gets to the mast cells.
We have a half-life of about nine days. Here's the biomarker in this space, tryptase, and what you'll observe here is a nice dose-dependent response in tryptase. Tryptase is released by mast cells, and that's an indication of the presence of mast cells. If you see tryptase going down, you know that your drug is affecting, it's either inhibiting the mast cell or it's depleting the mast cell. What you see is starting at about the 80 mg dose, you see that we are definitely inhibiting the mast cell, more than likely not depleting the mast cell at the 80 mg dose. At the 120 mg, you see the tryptase level almost reaching LLOQ or the lower limit of quantification, but at the 180 mg and the 240 mg, you're seeing the level of tryptase go below LLOQ.
That tells you that along with the durability here, that we're inhibiting the mast cell for certain, and we're more than likely depleting a significant number of mast cells with a single dose here as well. Remember the half-life of the drug and that PK. At the 240 mg, as an example, most of the drug is gone by four to six weeks, and yet we still have lower limit of quantification of reduction in tryptase. Here you'll see that translate into clinical outcome. Here's the UAS7 scores on these patients, and you'll see that drop. What you'll notice here, looking at the blue line and the red or the orange line, the 120 mg and the 240 mg, is that within one week, you see this dramatic drop in the UAS7 score of these patients.
By week two with the 240 mg dose, you see complete resolution. All three of the patients in that cohort had scores of zero, and they entered here with a median of about 27 as their baseline score coming into that cohort and went down to absolutely zero. What you'll also notice here is because of the dose intervals that we gave, as the 240 mg, as an example, that was a single dose. The patients, their disease starts to come back at week eight. However, we believe if we would have dosed them at week eight, we could have kept those scores to zero. Similarly, if you're looking at the 120 mg dose, and it's why I said in one of my lead-in slides, at 120 mg, it looks like maybe it's a Q4 week dose.
If we would have dosed at week four, instead of having those patients have an opportunity to rebound, we could have kept that score down because you see, I'll let your eye follow across to week eight on the X-axis on the 120 mg dose, you'll see what happens when we dose them then at week eight. Even though they rebounded, next time we gave it, now this time we drove them all the way down to zero. We think the 120 mg is probably a four-week dosing cadence. Here are the results looking in totality at the study, looking at complete responses, and what you'll see here is a nice dose response and complete response looking at four weeks after the second dose of briquilimab, with the exception of the 240 mg where it was a single dose, and so only looking at week eight in that patient population.
How does all this data stack up against the competition? Again, the only drug that's approved here is Xolair. The other three drugs in the middle, Dupi, Remi, and Barzo, are all in development. Should these data hold in a larger clinical trial? From an efficacy standpoint, briquilimab is looking to be superior at this point to those other therapies. We'll see, small sample size, but briquilimab is doing what we had hoped it would from an efficacy standpoint. Here's just another look at the 240 mg. Let's turn our attention to safety. Briquilimab has a very tolerable safety profile. What you'll see on this slide is treatment emergent adverse events, and interestingly, or not dissimilar to what's often seen in trials, are that the TEAEs are pretty similar between briquilimab and placebo. We did have one discontinuation related to a serious adverse event.
We had one patient who had a hypersensitivity. It's important to note that this was not an anaphylaxis. This case was reviewed by an independent adjudication committee. This is three individuals that are experts in this space, not investigators in the trial. They blindedly, we sent to them blinded the package, and they reviewed this case and deemed it to be a hypersensitivity and not an anaphylaxis. As I said before, c-Kit is present on other cell types in the body, most notably on the melanocytes, the taste buds, and the stem cells. It's also on the progenitor of the spermatogonia. The four most common adverse events that are observed by blocking c-Kit here are hair color changes and skin discoloration because of the effect on the melanocytes, hypogeusia, and the decrease in neutrophils. What you'll see here is hair color changes were similar to placebo.
We saw four patients here with no real dose-dependent relationship here. If you look over on the AE grading comments, the last bullet in each of the boxes gives you the doses that are associated with these emergent events here, and hair color changes, there was no dose correlation at this point in time. We did not see any skin discoloration. We did see six cases of hypogeusia. It's important to note that this is not like Paxlovid. Patients are not walking around with a specific type of taste in their mouth. It is an absence or diminishing of taste, and the six patients that were observed to have this said that they had a decrease in their ability to taste salt or bitter or umami.
Importantly, that the median time to resolution was only 31 days, so if you're getting this drug every eight weeks or so, you probably are only experiencing this maybe half the time that you're on drug. On the neutrophil count side, we did have one Grade 3 neutropenia. However, this patient had a history of idiopathic neutropenia, and it's important to note that while this patient did have this Grade 3 neutropenia experience on the first dose, they've gone on now to two additional doses of briquilimab and have not had another Grade 3 neutropenia. It does appear maybe with this patient that it was idiopathic here as well. Also, you'll see that there was no dose-dependent or at this point, nothing that relates to dose on neutrophils.
Important to note here that all of these, with the exception of that Grade 3 neutropenia, all of these cases were mild, transient, self-resolved before the next dose. No dose interruptions, no drug holidays, no discontinuation. The patient journey here will be significantly differentiated as we think about this related to maybe our potential competition in barzolvolimab. I'll show you here the data comparing our study versus their study. The data that they reported out at 16 weeks and then at 52 weeks, we just updated this slide, so our follow-up is now median of 30 weeks of follow-up, and both numerically as well as experience is significantly different. We had no discontinuations, no drug holidays. It doesn't appear as if we have any increase in accumulation, so it says 30 weeks of follow-up.
If we were to go back and look at the previous data set, this has not changed. Even though we keep following these patients out further, we're not seeing an effect because remember, our drug is being cleared from the system, so we're dosing to Cmax. Get in, hit the mast cell, clear it out, don't dose again until the mast cells start to come back. Where on the other hand, barzolvolimab is being dosed to an AUC.
They constantly have drug on board, so with the more and more continued saturation, probably explains as an example the hair color and the skin discoloration that the constantly inhibiting or exposing the melanocytes to c-Kit inhibition is bringing down the production of the melanin, and thereby you're seeing these numbers grow over a period of time where with briquilimab we wouldn't expect that, and now up to 30 weeks of follow-up, we haven't observed that yet. Let's take a look specifically at neutrophils. Neutrophils here, and I'll draw your attention to the orange line, the 240, so the highest dose we've tested to date. You'll see that an initial drop in the neutrophils, but importantly here, what you don't see is driving those neutrophils below the lower limit of normal.
Importantly, as we saw going back to the PK and the drug clearance, by about week four, the neutrophils start to recover. You see that briquilimab is losing its effect on those stem cells, so they are back to that production or they are getting back to that normal production. We think that if you extrapolate the neutrophils as a biomarker for those other c-Kit presenting cells, we might be able to see this same type of effect on those other type of cells and giving them recovery. We have a significant amount of data readout that will be coming in the mid-year. On January 8 in AAAAI , we updated on the first 49 patients from our study. Mid-year, we will have approximately 45 or more additional patients from those cohorts we added.
We'll have four additional patients on the 240 mg as a single dose, eight patients of 360 mg as a single dose, eight patients on 240 mg followed by 240 mg every Q8. Back to that question when we saw the complete responses through eight, what happens if we give them another dose? We'll be doing that, and we'll also be looking at 240 mg followed by 180 mg. Maybe the right thing to do is we lowered them more like an induction or a loading dose of that 240 mg. What if we backed off to a 180 mg dose as more of a maintenance dose? In addition to that, all of the patients in the BEACON study, those 49 patients are now eligible to roll over to an open label extension study, which is 180 mg Q8 week.
All of this puts us in a position to be able to start our Phase IIb adaptive clinical trial in the second half of this year, and if we maintain pace there, we'll be able to start Phase III clinical trial in Q4 of 2026. All of this is setting it up for briquilimab to, in a larger patient population by mid-year, really demonstrate the optimal biologic approach that can lead to a differentiated profile, which will lead to a differentiated patient experience by not giving up anything on the efficacy. If you saw how rapidly we were depleting those mast cells and getting reductions in UAS7, but also translating into a better safety profile, we look forward to a significant body of data coming this year and initiating our registrational program in the second half of this year.
With that, I'll open it up for questions. Yaron? I think they're—
Thank you, Ron. I appreciate it. Maybe a couple of questions. When we're looking at the data by mid-year, 45 additional patients, right? There's going to be both longer-term open label extensions, right? Plus you're going to try the 240 mg single and the 360 mg single. You'll have more of the 240 mg Q8, and then you'll have a 240 mg loading dose stepped down to 180 mg. How much follow-up do you think we'll have from those at that point, assuming, let's say, it's going to be sort of in the June-ish, early July at EAACI?
The minimum we would have is 12 weeks of follow-up. Whatever the last cohort in—these are all running and recruiting patients in parallel—but whatever the last cohort to fill, then 12 weeks after, so that'll be the shortest duration.
Some of the patients, like the 240 mg single dose, have been in for a while now. It will range sort of like what the BEACON study did when we announced those data in January. The shortest follow-up we had there was on the 240 mg single dose because that was the last cohort to fill. There will be a range from 12 weeks to up to a year.
At what point do you need to decide to start a Phase IIb in Q4? You probably need to decide the dose by mid-year or so, right? Roughly.
That's right.
In that Phase IIb , is there a placebo as well? There will be a placebo in that as well. It does not have to be one-to-one-to-one, right? It does not have to be one-to-one. You can hyper-enroll the other two dose levels?
Yes.
Got it.
The placebo, similar to the placebo in the BEACON study, it's largely there for study conduct. We want to make certain that both physicians and patients are blinded. Phase IIb will be significantly larger than what BEACON was, and it will be powered if we're able to show the type of efficacy that we observed so far in BEACON. It will be powered statistically.
As you think about, are you trying to maximize for sort of best data? Because based on your dosing, if you absolutely want to keep the trough and the max response at all point, I mean, you're getting some bounce back by Q8. If you dose every four weeks, it will be completely suppressed with a max reduction at each point, but at Q8, it does exhaust a little bit.
I think your point is when you dose again, you're retracing even a lower, deeper sort of low on—can you talk about that? Because that's going to be important as to how you think about dosing, whether it's Q8 or even Q12.
Yeah. Again, with a much larger sample size, we'll have data that will really tell us what isn't really well understood at this point is what's really the return kinetics of a mast cell. With this larger data set, we'll be able to look at a range of doses that tell us much more about the return kinetics of the mast cell.
In Phase IIb, do you have any sense what's the primary endpoint going to be or which week would you choose? Is it at 24 weeks? Is it going to be later? Is it earlier?
It will likely be 12 weeks at this point. We're having discussions with the regulators. Celldex has done 12 weeks. Remi did 16. I think it will largely depend on what is the dose interval we choose because the proper endpoint is probably four weeks after that second dose. That's probably the proper endpoint here. If it's a 12-week dose, then it would be a 16-week endpoint. If it's an 8-week dose, then it's probably 12.
I see. As opposed to waiting through two cycles, I guess it would be technically at that point, it would be three if you counted into—okay. Maybe when you're thinking about potentially new indications, I mean, you've talked about asthma. We're going to be waiting for another set of data on EOE. There's a signal already in PN with a class. Even as you think forward, at some point, do you want to partner this before you move into phase three? Is it something you could do alone, especially given the multiple indication opportunity?
Yes. As my opening slide stated, we see the franchise potential here, and there is no shortage of diseases. We are running an asthma study right now that will read out in the second half of this year that we are very excited about. We were just at AAAAI and met with CoFAR. CoFAR, if you know CoFAR from the food allergies, they are very interested in doing something in food allergies. If we are successful in asthma, it begs the question of COPD. The other commonality for all of those is those are very large markets, and those are the kind of things that pharma love.
Mast cells are a very hot target, and if you want the best approach, don't just ask me, but ask them. The best approach is depleting a mast cell, not inhibiting the mast cell. If you can safely deplete the mast cell, then its application is a really large opportunity, and this has the TI that pharma love.
Terrific, Ron. Thank you. I think we're at time. Really appreciate you coming in.
Thank you, Yaron.