Hello, hello. Good afternoon everyone, and thank you for joining me here at TD Cowen's 46th Annual Healthcare Conference. I'm Gina Han, and it is my pleasure to introduce Jeet Mahal, CEO of Jasper Therapeutics. As you all know, Jasper is an innovative company developing briquilimab, a c-Kit inhibitor for the treatment of chronic urticarias and other mast cell driven diseases. briquilimab has already shown really compelling phase I data in both CSU and CIndU, and we'll be starting a phase II-B trial in CSU in the second half of this year. For today, Jeet will give a presentation on the latest updates for Jasper, and at the end, we'll have some time for a kind of fireside chat Q&A situation. With that, take it away. Thanks, Gina. Thanks for joining us today. Happy to take you through Jasper Therapeutics and our work on briquilimab. I'll try to make the slide portion relatively short, so we can do Q&A, and then, you know, if you have questions, you can just let us know as well. First, these are our forward-looking statements. Jasper is really focused on the mast cell. Mast cell is a very interesting target for a number of diseases. A lot of different drugs and companies looking to target mast cells. If you think about a steward like Xolair, for indications, for 10+ years, asthma, chronic spontaneous urticaria, chronic rhinosinusitis, and now most recently, food allergy. Xolair works by clearing out IgE from the patient's system. IgE is the primary driver of mast cell degranulation. It's been a very successful drug. Now more recently, we've seen some new entrants to the mast cell space, namely Rhapsido from Novartis, with a recent approval in the United States for CSU, and DUPIXENT, of course, also with a recent approval for CSU. These competitive approaches do inhibit mast cell degranulation, but they leave the mast cell intact, and they leave other pathways that activate the mast cell intact as well. That's the difference between those pathways and targeting KIT. Mast cells use KIT as a survival pathway. When you block KIT signaling on mast cells, they undergo apoptosis and clear from the skin and the dermis and the lungs. We've shown this in primary biopsies for patients given briquilimab, as have others as well. You don't need to worry about subsequent or other pathways that could activate the mast cells because the mast cells are gone. To date, Jasper's done work in three indications of note here. First, the BEACON trial. That's our trial in chronic spontaneous urticaria. It was a phase I-B/II-A, a dose escalation study. We'll get into a little more detail in the next couple of slides there, but we're very encouraged by the data so far in the BEACON study and believe that our next stage of development will be to run a phase II-B/III in CSU. Our second study was a proof of concept in CIndU or chronic inducible urticaria. This is when the urticaria is done by a known trigger. The SPOTLIGHT study looked at patients with two known triggers, either cold and cold urticaria or pressure, scratching, otherwise known as symptomatic dermographism or ST. That data we've also reported, and we'll go through a little bit of that data today. Most recently, our last study, proof of concept study, was in patients with allergic asthma in the ETEOSIAN study. A very interesting study where we also believe we've shown proof of concept for briquilimab in asthma. First in the BEACON study. As I mentioned, the BEACON study was our first study in CSU. It was also our first multi-dose study. It was designed as a dose escalation study, starting at very low doses, 10 mg in a three-by-three design, before moving up to various other regimens in different dosing intervals. At this point, we've shown data for almost all of the intervals. The main key assessments here was the disease score UAS7. That is the disease score that is used for regulatory approval, as well as secondary markers such as serum tryptase, which is a marker of mast cell mass, and skin biopsies, looking at the mast cell presence or absence, as well as safety and PK. This was done in the U.S. and Europe in about 30 sites. First piece of data I'd like to take you through is some of the later cohorts. This is all the patients in the study that were dosed at 240 mg or higher their first eight weeks. This is looking at a marker called serum tryptase. Mast cells are the primary reservoirs of serum tryptase in the body. When they degranulate or get activated, this is one of the mediators that they release. They're also always producing serum tryptase, there's kind of a basal level of serum tryptase in most people. It's between, you know, five and 10 ng per ml. You can see here with a single dose of b riquilimab, we see the serum tryptase quickly drop by the end of week one and hold steady at these doses through about six weeks when the serum tryptase starts to recover. This is mirrored in the disease assessment. This is the urticaria activity score through seven days. They're known as the UAS7. At baseline, these patients are coming in with moderate to severe disease. The maximum score on this scale is 42. A 42 score indicates that the patient has journaled that they have severe itch and severe hives for each of the previous seven days. This is a pretty significant disease burden. In this study, we studied moderate to severe patients, and you can see again at the beginning that their disease scores were quite high. By week one or two, the briquilimab treated patients, and again, this is selected cohorts from the BEACON study along with our open label extension at 180 mg or higher, had rapid disease score control in what's known in this disease as a UAS7 score for patients that is zero for the whole week is considered a complete response, so no itch or hives on any of the preceding seven days. A UAS7 score of six or lower is considered well controlled. You can see even with the entire cohorts, we were getting rapid and deep control of the disease following the first shot, that disease control was holding through the end of the dosing period for the first four to six weeks and then starting to recover at week eight. Two of the cohorts in the red and blue line are single-dose cohorts, so they did not get a subsequent dose of drug, and you can see them, you know, come back up at week 10 or 12, whereas the other two cohorts received a 180 mg second injection at week eight, and we can see their scores going back down. Safety was also assessed in the BEACON study. Again, these are some of the later cohorts, although we also do show the pooled briquilimab and the pooled placebo. Nothing really significantly of note, in terms of serious treatment-related, serious AEs. There was only one patient with a CoFAR grade two hypersensitivity reaction in the 180 mg cohort. In terms of discontinuations, two patients with grade one or two hypersensitivity reactions and one patient with a grade three neutrophil count reduction that resolved within 18 days but did not lead to discontinuation. The second thing we want to look at in terms of safety and tolerability were AEs related to KIT biology. A number of other cells in the body also express KIT. Now, these cells are not survival-dependent, so when you block KIT signaling on these cells, they do not undergo apoptosis. However, they may be functionally dependent. Case in point are melanocytes in your skin that color your hair and your skin. melanocytes are not survival-dependent on KIT. However, if you block KIT signaling, they stop producing melanin. What we have observed in our preclinical toxicology data, as with competitive molecules, that if you inhibit KIT continuously for 12, 16, 20 weeks, you start to see graying in the hair and possibly hypopigmentation in the skin, little dots around the hair follicles where loss of pigment is seen. with BEACON, in the BEACON population, we did not see the hypopigmentation. we saw one case of slight hyperpigmentation, so a little bit of darkening, and that was also seen in placebo, one patient. and then in terms of hair color changes, we did see a slight uptick of patients experiencing hair color changes versus placebo. as you can see here, not something that appears to be dose-dependent. The other effects on this slide, taste changes, are noted. Again, your taste buds do have KIT. When you inhibit KIT, you do, as typically seen by our patients' experience, may experience a diminishment of taste. This is not a bad taste in your mouth. This is not described to us as metallic or anything like that. It's typically described as a loss of umami or a loss of sensitivity to umami, although other tastes can be affected as well. These are grade one events we've seen in the BEACON study that resolve while on drug within a few weeks, and almost all of them are first dose effects. It does seem that there's some sort of compensatory mechanism in the system to diminish that effect over time. The other effect that we've looked at, particularly, on focus were neutrophil count decreases. Neutrophils do not express KIT, so their activity level doesn't change, but their count may change because hematopoietic stem cells do express KIT, and by blocking KIT, you bias blood cell production away from neutrophils. Again, this does seem to be primarily a grade one event, not associated with infections or anything serious and resolving while on drug, typically within a week to a few weeks. Not something... None of this we think are big safety issues, although they may be tolerability issues. We were very encouraged by this data, given the length and the depth of disease control we saw earlier. Moving on to the second indication, inducible urticaria. We conducted the single-dose phase I/II SPOTLIGHT trial. These are patients with symptomatic dermographism or cold urticaria. You can see at the bottom, these are some of the tests that are used to ensure that these patients first have the disease and then evaluate their response. This was a single ascending dose study looking at single doses of 40 mg, 120 mg, and 180 mg. In the 180 mg cohort, and previous cohorts are available on our website. With the 180 mg cohort, which is the latest data, you can see that all 12 patients in this cohort achieved either a complete or a partial response by week eight. Over 2/3 had a complete response by the week two assessment. Again, very rapid and deep disease control that was very encouraging with regards to the activity of tezepelumab. Finally, tezepelumab in asthma was the ETEOSIAN study. Very fascinating study. This is mild to moderate patients with confirmed allergic asthma where we understand what their allergen is. The patients are actually given an inhaled solution of their allergen to trigger the asthmatic response where the lung function drops. First of all, we really wanna thank these participants for taking place in this study. They're confirmed to see the lung function drop. We give them either one dose of placebo or one dose of tezepelumab, 180 mg. At week six, we repeat the allergen challenge and assess lung function, changes tezepelumab, lung function changes to the patients who are on placebo, but no additional drug. We will repeat the assessment again at week 12. We saw first is the markers of the sputum eosinophils. These are cells that are recruited into the lung following allergen challenge. If you can see there, the blue bars are looking at allergen challenge one. On day 41, when the challenge is given, the sputum eosinophils are quite low. Day 42 and 43, you see the rapid recruitment of the sputum eosinophils that is not seen with the patients given tezepelumab. Then again, at the 12-week challenge, the challenge two, similar, recruitment of eosinophils in the placebo patients, and some recruitment with regards to the tezepelumab patients. 12 weeks after a single dose, we were not surprised to see diminishment of this activity. This is the FEV1 or the forced expiration volume. The other test we do in this study is the patients will blow, you know, at all the various time points here, these are in minutes, to assess their lung function volume. The lower the graph goes, the bigger impact the allergen has on affecting this volume towards the negative. What you'd like to see is the fact that there's no change. You, you know, wanna see something that's close to a straight line at zero. That would indicate that there's no impact of the allergen whatsoever. On the left-hand side in the placebo graph, you can see that the solid line, that was the pre-dose assessment of lung function, overlaps with the week six and the week 12 challenge. The placebo really not showing any effect in these patients. On the tezepelumab side, you see again the solid line, which is the pre-dose challenge. Before we give the tezepelumab, it's significantly below that of the post-dose challenges. At week six and week 12, we see less of an impact on the allergen following a single dose of tezepelumab than we saw before. The patients can kinda serve as their own controls here. Finally, looking at the future plans for the company, we're looking to start a phase II-B/III study in chronic spontaneous urticaria in the second half of this year. We'll be taking two doses versus placebo, and then looking at that data at the end of next year, through the 12-week assessment period. Based on that data, we'll select one dose to move forward into a phase III study and start a second phase III study at the same time. With that dose information, we're also planning to start a third phase III study in chronic inducible urticaria. As we approach the market, we're able to come out of the market with both indications for induced and spontaneous urticaria. The asthma data is very interesting for us as well. For now, we have not determined the next steps of the program. We would consider a phase II program sometime in 2027, depending on, you know, financing or other capabilities at the company. Finally, we wanna note that, you know, mast cell-associated diseases are not limited to just the ones we mentioned with Xolair. There's a lot of great evidence out there, preclinical or otherwise, that this may be important in COPD, IBD, prurigo nodularis, and other diseases. Jasper owns full worldwide rights to develop and commercialize tezepelumab in all indications. Thank you. Great. We went to the Q&A portion. I have some questions prepared, but obviously if at any point anyone in the audience has any questions, just raise your hand and we can ask the question here as well. To start off with, you mentioned that you'll be starting this phase II-B CSU study second half of this year with two active doses versus placebo. Yeah. I was curious how you're currently thinking about the dose selection, given that I think you're doing a few further analyses to determine which two doses to take into this phase II-B? The first thing we wanna emphasize is we're planning to take two very effective doses into the phase II-B. We have enough information to understand the dose exposure response now in this population. It's really about what's the right commercial profile. By, you know, doing this in a phase II-B setting, we'll be able to then make the choice about which of the regimens to take into phase III. What we've seen with competitive molecules is that if you keep the KIT signal suppressed throughout the dosing period, you have very deep efficacy that builds over time. You know, that likely will be one of our regimens. The other regimen, we'd want to think about testing the unique properties of upacolumab that we think could still maintain that efficacy, but with a better safety profile. namely, as we've shown today, we would want a little bit of time at the end of that dosing cycle for KIT signaling to return to the non-mast cells, then thereby, you know, potentially diminishing the effects of the on target KIT effects. One arm we're gonna keep that KIT receptor saturated, and in the second arm we're gonna really try to test a profile that could be differentiated on both efficacy and safety. Right. If I read between the lines a little bit and consider your previous data, I think maybe one of those doses will be kind of a fixed every eight-week or so regimen, kind of more consistent, and then maybe at the other dose regimen would be something with a loading dose and then maybe a lower dose or a longer interval. Yeah. You know, that's what we're doing right now. We have quite a bit of data between the BEACON study, the SPOTLIGHT study, the open label extension to those studies, which we did not cover today as well. The, the best way I'd like to think about it is based on the pharmacology of the drug and the data we've seen to date, how do we still maintain that efficacy on the front end that we saw, that very rapid drop in tryptase and the UAS7 score, but do it in a way where we can recover some of that KIT effects? We've seen other drugs in I&I that do it different ways in terms of dose selection. You can think about maybe doing something where we have a weight adjustment, so a drug like STELARA, one drug up to 100 kilos and another dose above 100 kilos. Not anything complicated, but where you can really take advantage of the pharmacology and the data you've seen to date. Other way of doing it is possibly something like TREMFYA, which is, I believe, week zero, week four, and then Q8W, right? If you have a kind of an induction, you know, schedule, which is kinda common in psoriasis before backing off, you know, to kind of improve the safety profile. you know, we're definitely think we have an eight-week drug here, but we haven't made the final determinations of the doses or the dose schedules. What kind of analyses are you still waiting for to make this decision, and kind of what do you think is the timing on that? Yeah. The timing's pretty close, right? We released the, this data in mid-January, so it's really only been six weeks or so, right? you know, you know, even though we have a stack of professionals inside the company and outside of the company helping us with this, we haven't quite finalized them, although it's not very far, right? Some of the things we wanna consider, of course, is our observed data, our observed PK, our observed PD, and our observed UAS7 data, our observed safety data, but also incorporate, you know, modeling into this as well. you know, with the ends we see here with the patient population sizes may not be reflective of either the clinical population or the eventual commercial population, so we do wanna take that into account as well. You know, we build a model for both the PK and the PD, and then finally the UAS7 response and we will run these, the various options in terms of all the different dose options out there before selecting the final one. Not much farther to go, but we're trying to do a fairly comprehensive job, at dose selection. Right. How do you think patients are kind of weighing the advantages and disadvantages of having a drug that might be more effective but with more side effects versus tolerating a few more AEs? Yeah. You know, I think every patient kind of goes through the same checklist when considering a new therapy. How well does this drug work? How fast does it work, and what happens to me when I take it either once or on a long time, right? What we believe we see right now with the KIT inhibitors is that they have the best in disease profile with regards to efficacy, both in terms of the number of patients or percentage of patients that reach a well-controlled or CR status, but also how fast the onset is. As you saw with the upacolumab data, we're seeing deep UAS7 drops within two weeks, two to three weeks, right? We do think those are very favorable pieces of this profile for such a severe disease. Remember, like, it's itch and hives, right? These patients have significant disruptions in their life, right? Their KOL, their sleep, their work, their ability to go outside, depends on the disease you have, right, you know, your mood. We do think that the, you know, the effect here, the efficacious effect here is worth a lot to these patients. At the same time, you know, there's no reason to have these KIT-related AEs if we can do something to design them out of the profile 'cause, like, I have some gray hair, you know. Do I want more? Not really, you know. Skin hypopigmentation, I can't imagine that, you know, anybody would like that either, right? Again, this is a pretty severe disease, so I'd say that's secondary to efficacy, but still something we're gonna do our best to engineer out. Right. As you say, I think that when we talk to KOLs, they always mention c-KIT as kind of the most promising mechanism on efficacy. Now that you have DUPIXENT, Rhapsido, XOLAIR all kind of approved for CSU, where do you think the c-KIT inhibitors will be positioned in this kind of treatment algorithm for CSU? Yeah. For both CIndU and CSU, the first step is high-dose antihistamine 4x the label dose, right? The question becomes, if a patient's still not responding, where do we go? For years, the only choice we had was Xolair, right? Xolair is given either every other week or every four weeks, and there's a very complicated schedule in their label about patient weight and amount of IgE a patient has in their system. If it's too high or too low or they're too heavy or too light, then Xolair doesn't work for you. It's a drug that the allergist community knows well-That works good in CSU. They do not have an indication for induced urticaria. There may be some reports of it being used off-label, I mean, again, this is a drug that's 10-plus years old. You know, the data, pretty good for Xolair. It's a well-known drug for CSU. For the other two new entrants, you know, it's more mixed, right? DUPIXENT, I think, all the derms know about. It's, you know, the top in class for atopic dermatitises, of course. You know, Sanofi failed the study versus in chronic inducible urticaria. They failed the study for Xolair refractory patients. Overall, the least efficacious rates of CR well-controlled disease. Although it's a well-known drug and used in derm offices, it's really not delivering the efficacy that the other ones are. You know, some of the derms tell us that, you know, maybe if I have a patient with overlapping label indications, so that'd AD and CSU, DUPIXENT could be of interest. For the allergist, it's not a drug they really use, you know, We're not sure how this is going to overtake Xolair, which is a drug they have been using and has, is considerably more efficacious, at least from in regards to their label, how that's gonna go in front of them. We think that, you know, DUPIXENT is a new therapy. You know, look, right now for years, nobody's had other things to try, folks are gonna try it. You know, if their phase III efficacy is reflective of real world rates, it's gonna be kind of the bottom of the barrel for efficacy in these drugs. Rhapsido is an oral BTK inhibitor from Novartis dosed twice a day. Onset is good, very good, you know, pretty quick. Overall CR rates are a little bit less than Xarelto or than Xolair, pretty strong. Of course, you know, BTK is across your entire immune system in terms of any Fc receptor, all your other immune cells that use antibody signaling, your B cells and things like that, BTK will shut those down as well. I think the question then becomes, with BTK, you know, how comfortable are derms using a class of drugs that we know have a pretty broad immune suppressive effect when they might have other choices? The final thing about, you know, where these drugs are positioned, I'll say, is that the way patients are diagnosed with chronic, you know, spontaneous urticaria is pretty interesting. They come to their derm or their allergist, and they have these itchy wheals for at least six weeks, and then the protocol is to see if you can induce it, right? Are these wheals triggered by cold or heat or pressure or exercise? There's a few others, right? Basically, you're trying to see if these patients have CIndU. If they don't have CIndU, then it's CSU. It's a diagnosis of inclusion. We do think it's really important to have a drug that has both indications, right? If you're a physician, it makes your life a lot easier to think that, "Look, I, I know I can give a c-Kit inhibitor to any of these patients," right? "I know it's gonna work on the first shot. If it's gonna work, I'm gonna know in a few weeks," right? Then after that, I can maybe go through the other therapies. Look, maybe we don't start, you know, at first line after antihistamines, I think the profiles there that, you know, that could be the ultimate, market position. Right. Makes a lot of sense. Stepping back from CSU a little bit, what do you think would be the optimal financing strategy for you at this point? Are you looking for a strategic partnership, some kind of co-development, just a straight-up raise? Yeah. You know, financing of course, you know, is the lifeblood of biotechs, and we're no different. We, you know, we need to raise money in order to do the next set of studies here. The good news for where we are right now is for this phase II-B is that the drug's already been manufactured. You know, still need to do some final kitting and labeling. The protocol's gone through first round reviews at FDA and EMA. We need to go back of course, right? It's really about, you know, financing the company and getting this study off the ground. We've looked at all the various opportunities, you know, options, right? At this point, you know, we don't think that project-based financing companies are really built for assets at this stage. They're typically phase III programs, right? We're not quite there. Although, you know, we continue to talk to them. In terms of strategic partners, you know, we'll see. You know, I think that what we've seen with our data and the Celldex data is that this is a very promising class, but strategic partnerships take a long time. They're very slow to consummate, right? We do think that equity financing, you know, is probable. That's probably in our near term future, but we continue to look through all the options. Right. Right. Makes a lot of sense. I think we are at time now. Thank you, Jeet. Yeah ... for joining us today. Thank you. Thank you everyone for attending. Yeah. Thanks. Thanks all.