Jasper Therapeutics, Inc. (JSPR) Earnings Call Transcript & Summary

Good day, and welcome to the Jasper Therapeutics SPOTLIGHT Data Update Conference Call. [Operator Instructions] Please note, today's event is being recorded. I would now like to turn the conference over to Alex Gray, Head of Investor Relations. Please go ahead.

Thank you, operator, and thank you to those listening in today. Joining us for the prepared remarks is Ronald Martell, CEO. Also on the line is Herb Cross, CFO. We will be presenting slides on today's call, which are available via the webinar link posted to our Invest Relations website. The slides available through the webinar link are presenter controlled, and we will be referring to slide numbers as we proceed through the presentation. Moving to Slide 2. During today's event, we will be making forward-looking statements based on our estimates and assumptions and our current expectations and projections about future events. All statements other than statements of historical facts made during today's events are forward-looking statements. These statements are subject to a number of risks, assumptions and uncertainties, any of which may be significant, and our actual results may differ materially and adversely from those stated or implied in any forward-looking statements. For a description of risks and factors that could affect our future financial results and business, please refer to the disclosure in the accompanying slides, our most recent Forms 10-K and 10-Q and the reports that we may file on Form 8-K with the Securities and Exchange Commission. All our statements are made as of today, June 16, 2025, based on information currently available to us, can give no assurance that these statements will prove to be correct, and you should not rely on any forward-looking statements as predictions of future events. We undertake no duty to update any forward-looking statements, except as required by law. We'll now turn to Slide 3, and I'll hand the call over to Ronald Martell. Ron?

Good morning. I'm Ronald Martell, CEO of Jasper Therapeutics. On behalf of my colleagues at Jasper, I'd like to welcome you to our conference call to present the data from the 180-milligram cohort of our Phase Ib/IIa SPOTLIGHT clinical trial evaluating briquilimab in chronic inducible urticaria or CIndU, following our presentation at the European Academy of Allergy and Clinical Immunology Annual Congress on Saturday. Before walking through the data in detail, I'd like to say how excited we are to be presenting such robust clinical data. It's remarkable to see all 12 patients enrolled at the 180 milligram achieved a clinical response with 11 of 12 achieving a complete response. Overall, 96% of patients enrolled in the SPOTLIGHT study at any dose achieved a clinical response and 81% achieved a complete response with the deepest and most durable results observed at the 180-milligram dose level. We're also very encouraged by the promising safety and tolerability profile that we continue to see in our studies of briquilimab across indications, which is reinforced by the new data we're reviewing today. We believe that these data provide strong positive read-through to our other clinical programs in mast cell diseases. And I will discuss our next steps in CIndU as well as the upcoming milestones in our CSU and asthma programs. Turning to Slide 4. Before we review the efficacy and safety results from the SPOTLIGHT trial in detail, I'd like to describe the high unmet medical need with CIndU. Turning to Slide 5. Chronic inducible urticaria is a debilitating condition of the skin and in severe cases, involves other organs, including the airway. There are many triggers for the hives, itch and weal that are characteristic of urticaria, including heat, cold, sunlight, water and abrasion, each of which constitutes a subtype of the disease. For the 2 most prevalent subtypes of our symptomatic dermographism or SD, caused by skin abrasion and cold urticaria caused by moving from warm to cold environments, such as air-conditioned rooms or immersion in cooler swimming pools. Mast cells are central to the pathophysiology of CIndU with degranulation leading to release of inflammatory mediators creating the symptoms of each disease. The most severe outcomes of cold urticaria, for example, can result in laryngeal edema and life-threatening asphyxia. For most patients with CIndU, physical, social and psychological impacts are significant impairments to quality of life, similar to other derm disease such as psoriasis and atopic dermatitis. Beyond antihistamines, there are no approved treatments available globally for patients with CIndU. The development of KIT inhibitors to deplete mast cells may offer a new treatment paradigm for these patients, reducing the disease burden and improving the quality of life. Moving on to Slide 6. The trial enrolled adults with 2 types of CIndU, SD or symptomatic dermographism and cold urticaria, refractory to antihistamines and assessed ascending single doses of briquilimab from 40 milligram to 180 milligram and was conducted at trial centers in the EU. At this point, we have completed enrollment in all 3 cohorts of the study, and patients who have completed the study are eligible to enroll over into our open-label extension study, evaluating 180 milligram of briquilimab dosed every 8 weeks. Our key efficacy assessment in CIndU are the TempTest and the FricTest and the UCT scores during a 12-week observation period. In addition, we also measure serum tryptase through the course of the study and observed safety and tolerability of the drug. The lower panels show the evaluated provocation tests for each CIndU subtype in the trial. The FricTest is a 4-point assessment and 0 indicates a complete response with a partial response being 2 or more pin improvement. The TempTest measures the temperature threshold at which hives occur. A complete response is achieved when the test is negative or less than 4 degrees Celsius. A partial response is a 4-degree Celsius improvement from baseline. Today, we are presenting an 8-week preliminary analysis as all patients enrolled have now passed the 8 weeks post-dose observation period. On the next slide is a top line summary of the remarkable safety observed -- remarkable efficacy observed in SPOTLIGHT. As I previously noted, 12 of 12 participants enrolled in the 180-milligram cohort achieved either a complete response or a partial response within the 8-week preliminary analysis period. This is compared to -- with 11 of 12 participants at 120 milligrams. Furthermore, 92% of participants at 180 milligrams achieved a complete response compared with 83% at 120 milligram. The responses observed were correlated with deep reductions in tryptase measurement with 10 of 12 participants at 180 milligram going below the lower limit of quantification. As reported in previous readouts, briquilimab demonstrated a rapid onset of effect with 67% of participants in the 180-milligram cohort, achieving a clinical response by week 2. Finally, we are pleased by the durability of effect observed with 58% of participants at 180 milligram maintaining clinical response at the week 8 assessment. Slide 8 summarizes the baseline characteristics of the 2 cohorts. Overall, the age, weight and gender of the participants align with expected patient demographics in CIndU. Across the 3 briquilimab cohorts, baseline FricTest and Cold TempTest indicate high disease burden. As expected, that participants were refractory to antihistamines prior to enrolling in the study. Baseline UCT scores for each cohort also indicate a high disease burden. UCT is a measurement on a 16-point scale with a score of 12 or more defined as well controlled and a score of 16 defined as complete control. Slide 9 shows mean serum tryptase measurements over time for all 3 cohorts. We see a rapid drop in tryptase by day 8 with a clear dose response on the depth and duration of the reductions in mean tryptase measurements. Mean tryptase in the 180-milligram dose cohort drops below the lower limit of quantification by day 15 and mean values for both the 120-milligram and 180-milligram cohorts remain below baseline through week 8. The rapid decline in tryptase, consistent with KIT blockade and seen in our other studies correlates with rapid onset of clinical response as we observed in 8 of 12 participants who achieved a CR or a PR by week 8. The next slide, Slide 10, shows the robust dose-dependent efficacy observed at each dose. 100% of the 180-milligram dose cohort achieved a clinical response with 92% of patients, 11 of 12 achieving a complete response by week 8. Both represent increases over the 120-milligram dose cohort in which 92% or 11 of 12 achieved a clinical response with 83%, 10 of 12 achieving a complete response by week 8. 8 of 9 participants in the 180-milligram cohort with symptomatic dermographism achieved a complete response and the remaining patient achieved a PR. For the participants with cold urticaria at the 180-milligram dose level, 100% or 3 of 3 achieved a complete response. Across all dose cohorts, 40-milligram, 120, 180 milligram, we saw 26 of 27 participants, 97% achieved a clinical response. The figures on Slide 11 show response rate observed over 8 weeks in the 180-milligram cohort, demonstrating rapid and durable disease control, consistent with the predictable pharmacokinetics seen in other -- in our prior study results as well as the rapid and sustained reduction in tryptase. As you can see, 2/3 of participants at the 180-milligram cohort achieved a clinical response by the week 2 assessment with 100% of patients achieving a clinical response by 8 weeks, 11 CRs and 1 PR and 58% of patients maintaining a clinical response through week 8. The next slide, Slide 12, shows a snapshot of clinical responses observed at week 6 assessment, showing clear dose response across the 3 cohorts with depth and durability of responses. At week 6, 92% of participants at 180-milligram cohort had clinical responses compared to 58% of participants with the 120-milligram dose cohort. Similarly, the complete response rate at week 6 was 75% for the 180-milligram cohort versus 50% for the 120-milligram dose cohort. Moving to safety on Slide 13. Briquilimab was well tolerated at all 3 dose levels evaluated in the study with no discontinuations observed due to adverse events or safety issues. Since data from the 120-milligram dose cohorts were previously disclosed, I will focus on the 180-milligram cohort. At 180 milligrams, there were no serious adverse events reported and no Grade 3 or higher adverse events. Adverse events occurring in greater than 3 participants in the 3 cohorts included nasopharyngitis, neutrophil count decreases, fatigue, headache, abdominal pain and COVID-19. Overall, we continue to be very pleased with the safety profile of briquilimab observed in CIndU as well as CSU. The next slide, Slide 14, shows safety and tolerability of observations possibly related to KIT blockade, which continue to be limited to low-grade transient events. All events reported at the 180-milligram dose level were grade 1 or 2 and none resulted in discontinuations, which is consistent with what we've seen across dose levels in both SPOTLIGHT and BEACON. There were no reported hair color changes or skin discoloration in the 180-milligram cohort or any dose cohort in this study. Taste changes were observed in 2 patients at the 180-milligram dose level and were mild and transient, consistent with prior observations. Neutrophil count reductions were reported in 6 participants at the 180-milligram dose level, all of which were mild, low-grade and transient events with 4 grade 1 and 2 Grade 2 events and a median time to resolution of 16 days. 5 of the 6 patients with neutrophil reductions at the 180-milligram dose level were diagnosed with a common cold or COVID-19 proximal to the observation of these reductions, which is important to note given that viral infections are well understood to drop -- result in drop in neutrophil counts. Also, this incidence can be accounted for by the cohort being enrolled during the winter season in Northern Europe. Most importantly, and consistent with prior clinical data, those mild grade reductions in neutrophils were transient, self-resolved in a median time of 16 days and were not associated with any clinical sequelae. Slide 15. Wrapping up discussion on neutrophil counts. Slide 15 shows that the mean AMC over the first 8 weeks following dosing for the 40 milligrams, 120-milligram and 180-milligram cohorts. Consistent with our clinical experience to date with briquilimab, given the mild, transient and self-resolving nature of the neutrophil count reduction observed, the mean neutrophil count levels for each cohort remain within the normal AMC ranges throughout the 8-week observation period. Moving to key takeaways from these data. We believe that further -- they further reinforce the potential for targeting KIT on mast cells with briquilimab to deliver rapid, deep and durable clinical benefit in mast cell-driven diseases. In the 180-milligram cohort, we saw tryptase reductions in 83% of participants to below the LLOQ, rapid onset of clinical benefit with 67% of participants achieving a clinical response by week 2, deep clinical benefit with 100% of participants achieving a clinical response over the course of the 8-week observation period and highly durable responses with 92% of participants maintaining their clinical response through week 6 and 58% of the participants maintaining clinical response through 8 weeks, including 5 complete responses at that time point. On the safety front, briquilimab continues to be well tolerated with no grade 3 adverse events or serious adverse events observed at the 180-milligram dose level. with events possibly related to KIT blockade continuing to be infrequent, transient, low-grade events that self-resolve on therapy. We are excited to see additional evidence of briquilimab’s robust efficacy and safety that further supports advancement of briquilimab into registrational studies in both CIndU and CSU. And finally, we look forward to presenting full SPOTLIGHT study results at a medical conference in the second half of 2025. We are pleased with the progress made in our development program and continue to share our clinical data updates from SPOTLIGHT and BEACON studies. With this new SPOTLIGHT data in hand, we are able to inform a further registrational study in CIndU planned for 2027. Our near-term operational focus continues to be directed towards delivering our BEACON clinical study update in CSU, in the early third quarter of this year. Early work in support of the commencement of the Phase IIb portion of our CSU registrational program in the fourth quarter of 2025, and we have guided to our initial clinical data from our ETESIAN study in asthma in the second half of 2025. We are excited to now have briquilimab clinical efficacy and safety demonstrated in 2 indications at therapeutic dose levels. And we expect to share further data from the BEACON study later this year, which will inform our dose selection for the Phase IIb study as part of a CSU registrational program. With that, I'd like to open the meeting to questions. Operator?

[Operator Instructions] And today's first question comes from Gavin Clark-Gartner with Evercore ISI.

This is Yesha, on for Gavin. We were just wondering if in the 2 Grade 2 neutropenia cases, if you could touch on if the neutrophil counts rebounded above 2,000 in these patients.

Thank you for the question. Yes, in -- not only in those 2 Grade 2s, but all of the patients who had any decrease in neutrophil count, their counts rebounded to above 2,000. And again, with that median recovery time of 16 days, so relatively quick response across the board.

And our next question today comes from Yaron Werber with TD Cowen.

This is [Jana], on for Yaron. I was wondering, I know that these -- there's no approved therapy for CIndU, but were there any patients on the study who had previous exposure to Xolair, perhaps off-label?

There were no patients in the study who had or at least no reported exposure to omalizumab.

And if I could add one quick follow-up. Could you give us a breakdown of whether the taste changes were Grade 1 or Grade 2 and the time course for recovery?

They were Grade 1, and we don't have at this time of reporting the time to resolution.

And our next question comes from Leonid Timashev with RBC Capital Markets.

I wanted to ask on the baseline characteristics. I mean you mentioned that some of these patients were pretty challenging. So I guess I'm curious how you think this compares both to patients you've seen in the real world, how it compares to patients on other competitor studies? And then just in general, whether you're seeing any correlation between any of the baseline characteristics and potential depth of response or durability of response and how you think that might evolve as you advance to more advance study?

Yes. Thank you. So I think that the -- well, I say I think I was at the EAACI meeting this weekend and attended a symposium on inducible urticaria, and the baseline demographics here are pretty consistent with the patients that seek treatment. So this is pretty representative of the patients who have symptomatic dermographism and cold urticaria. Regarding the depth of response and durability to date, while this is a small sample size, represent a significant advancement to any of the other clinical trials that have been conducted with the other agents that are in development that either target KIT or that target other mechanisms such as X2, the results both in time to onset of clinical response, the level of complete response or partial response and the durability of response. Remembering that these were single doses of briquilimab and the durability of seeing those level of clinical responses at week 6 or week 8 represent the most durable responses that have been observed in clinical trials to date.

And our next question today comes from Matt Phipps at William Blair.

I was curious at this point, whether you think kind of watching serum tryptase levels might be able to guide kind of retreatment guidelines timelines? And then could you remind us on just kind of the time gap between a patient getting this dose and then being able to be enrolled into the OLE? Just trying to figure out maybe how many patients would have seen multiple doses in the OLE at the 180 mg Q8 week regimen that we might get in that upcoming update in Q3.

Sure. So first, with the tryptase. So tryptase continues to be an important biomarker from a cohort basis, it's not a great predictor on an individual basis. As a reminder to all, mast cells in these diseases are not pathogenic or diseased. These are normal mast cells like you and I would have if we don't have either of these diseases. So the baseline levels of tryptase are consistent with normal mast cells. So at the starting point, there's not a biomarker value for doing an assessment and looking at the level of tryptase at baseline. What is important is that you reduce the tryptase levels to LLOQ or below, meaning you completely shut down the signal to the mast cell, thereby tryptase is not produced. And the longer you -- or deeper that you reduce tryptase is associated with not only mast cell inhibition, but mast cell depletion. And I think on the trailing edge for the return of the mast cells, there does seem to be a correlation with an increase in tryptase about 2 weeks before you start to see a reduction in clinical efficacy or a loss of clinical efficacy on a cohort level, but on an individual patient level, it doesn't carry that level of predictability. We'll continue to monitor it. But I think most importantly is making certain that your drug level is making tryptase drop below LLOQ, which we see here in this study, and we see sustained levels of that or durability of that. Regarding the OLE, so once patients in both the BEACON and the SPOTLIGHT study complete their 24-week follow-up period from the single dose, then they're eligible to participate in the OLE. And what we've observed to date is that all patients who have been eligible to go into the OLE have elected to participate. Now to be clear, when I use the word eligible, if patients after their 24-week observation period elected to go into a different clinical trial, then they would not be eligible for the open-label extension. And we did have a few patients, especially at the 40-milligram level because they concluded their -- they concluded their 24-week observation period some time ago, and the OLE was not available to them, but we're very pleased that for those patients who have been offered the open-label extension, they've all decided to participate. And we would anticipate having that multi-dose cohort data coming up here in the second half of this year.

And our next question today comes from Pete Stavropoulos with Cantor Fitzgerald.

Congrats on the data. Two questions. First one, on Slide 11, there's a progressive increase in complete responses with time, 50% at 2 weeks, and that climbs to greater than 70% at week 6. Those patients that took a little longer to have a complete response, was there anything notable about their baseline characteristics or kinetics or depth of tryptase reduction?

Thank you, Pete. Yes, that was a great observation on your part here. So there didn't -- there doesn't appear to be any difference in the baseline characteristics for those individuals who had a furthering of the response or a deepening of their response over the period of time. And it likely just has to do with the time it takes to inhibit and then deplete those mast cells, and the apoptosis associated with that.

Okay. And second question, you also presented additional data for CSU. You look at the UAS7 and the UCT scores, the 240 milligram has a quick onset and complete control by week 2. And the 120-milligram and 180-milligram QAW had a deepening response for those assessments after the second dose. How do those data sort of point or impact your thoughts around using a loading dose in the later studies of 240 milligram or even taking the 240 forward as a chronic dose?

Yes. So you're referring to the -- when you say additional data that we presented at EAACI -- BEACON study was selected for an additional flash talk presentation at EAACI, and we presented data from the BEACON study on the UCT data that had not been previously reported. And yes, there's -- looking at the UCT scores, there is a clear dose response as we presented here in the SPOTLIGHT study as well. And I think what that further reinforces to us, Pete, as you point out, is that at the 240-milligram level, we saw all 3 subjects, 100%, achieved complete response by week 2 with many of those patients having a meaningful clinical response at week 1. So very rapid onset here and deep and durable complete responses maintained out to week 8. That reinforces to us that the 240-milligram dose level really drives meaningful responses here. Having said that, we'll be reporting out in the first half of Q3 more data on the single dose with 240 as well as 240 every 8 weeks and 240 followed by 180 to look for both safety and efficacy. We're very fortunate here with the properties of briquilimab in a 9-day half-life that we can optimize for not just efficacy, but for safety. And likely moving forward, the 240 will be one of the doses that we move forward into the Phase IIb, and it could be as a loading dose.

And our next question today comes from Silvan Tuerkcan with Citizens.

Congrats on the data. I just had a quick question on the -- maybe if you can touch on how the clinical response rate that you presented from 6 to 8 -- or it seems to increase from 29 days to 43 days, while the, I guess, cohort tryptase levels are kind of rebounding. Is there like a lag where like tryptase may be rebounding, but your symptoms are still or response that is still continuing to improve? And what's your big takeaway from, I guess, the response rate at 8 weeks with respect to the 8 weeks and 12-week dosing regimen in CSU?

Yes. So the delta between the week 6 and the week 8 with the 120 and the 180 to us show that the 180 is more potent, is depleting more mast cells, thereby providing more durability and an additional 2 weeks of exposure. And that's consistent with what we observed in the BEACON study, where the 120-milligram dose level appeared to be maybe a 4- to 6-week dose and the 180, a 6- to 8-week dose here. And that was confirmed here in the SPOTLIGHT study as well. Regarding the tryptase and the association with tryptase here is, again, it appears in both the BEACON and the SPOTLIGHT study that when the tryptase level starts to rebound and approach the LLOQ or goes above the LLOQ as a cohort level now, not on an individual patient basis. But it appears when that begins to happen that you have about an additional 2 weeks before you start to lose or have diminished clinical efficacy. And I think the take-home for us moving forward is that briquilimab will likely be dosed on a Q8-week basis and that a Q12 regimen is probably a bit too far for us to achieve, and we think we can optimize for both efficacy and safety around the Q8-week dose.

And our next question comes from Justin Zelin at BTIG.

Congrats on this data. Maybe just to follow up, I just want to make sure I heard right that you're looking to use briquilimab in every 8-week dose regimen in this data that you're showing here in SPOTLIGHT, would that be at this dose, the 180 mg moving forward?

Justin, so based on these data, yes, it reinforces that briquilimab could be an every 8-week drug. Having said that, we will make the determination on the dose for the Phase III portion or the Phase III study in CIndU largely based off of the data set from BEACON that's coming this year. Because, again, in both of these diseases, it's the common mast cell, and we'll have a much larger data set from BEACON that will inform us on what's the optimal way to dose a mast cell. And so once we've chosen that dose for CSU, there's a strong read-through as there's a read-through from this data to CSU, there's a read-through from the CSU study back to this one to inform us what our dose that will be. So likely whatever dose we choose for the registrational studies for CSU will be the dose we choose for CIndU.

That makes sense to me. And I think I heard earlier that you also mentioned that from your data from the BEACON study, we can also look out for whether you will be using a loading dose in that dosing regimen moving forward, correct?

That's correct. As a reminder, in the BEACON study, we are studying 240 as a loading dose. We have a cohort that is enrolling 240 as a loading dose and then 180 Q8 week. In addition to that, given the safety profile we observed at 240 and the efficacy we observed there, we have also enrolled a cohort of 360-milligram single dose, which will give us insight to both the depth of response, the durability of the response and the safety at 360, such that 360 could potentially be a loading dose in the urticaria indications, and will help inform us for other development in other diseases again, because the commonality here is the mast cell. And it does appear that in a variety of other mast cell mediated or mast cell-driven diseases like asthma that we're currently studying or food allergy that we have a high interest in or others that the mast cell, again, in all of those diseases is not diseased or pathogenic. So there'll be a strong read-through and really informative for us to accelerate advancement of clinical development in those other diseases.

And our next question comes from Emily Bodnar at H.C. Wainwright.

I kind of wanted to ask a bit more about the earlier points with the Q8 weekly dosing. So it looks like you're starting to lose some of the responses between week 6 and week 8. So would you expect that when you dose patients again at week 8 that those patients who maybe lost response would kind of go back into having a complete or clinical response? And do you think with longer-term dosing that those kind of declines around the 6- to 8-week period would tend to go away?

Yes, we would expect that -- exactly that to happen. And I base that on 2 things. We observed that in the BEACON study. And if you go back and look example at the 120-milligram dose level and BEACON achieved significant clinical responses, not to the depth that we saw with 240, but we saw deep clinical responses with rapid onset, but those responses were only durable through a 4-week period. And in the BEACON study, we were dosing 120 every 8 weeks, and there was a rebound of the clinical symptoms almost back to baseline by the time they were dosed again at week 8. Yet when they were dosed at week 8, those same patients this time the cohort went to a level of complete response. And so we would expect that we would see that. And we've also -- if you look at the Barzo data, they've observed the same thing. So in the preceding weeks, generally, it looks from the data we've observed that they start to lose the clinical efficacy about 2 weeks before the next dose of Barzo. And then after a subsequent dose, they see a deepening clinical response. And I think it's important to note here that the efficacy we observed at week 8 after a single dose of briquilimab exceeds the results that have been observed with Barzo. I recognize I'm discussing cross-trial comparisons. But if you look at the 12-week data for barzolvolimab and their CIndU study, that 12-week data was, in fact, 4 weeks after either your third dose of 150 or your second dose of 300 and yet our results at 8 weeks are comparable to what they saw 4 weeks after their second or third dose.

All right, thank you. And this concludes our question-and-answer session and today's conference call. We thank you all for attending today's presentation. You may now disconnect your lines and have a wonderful day.