Good morning, everyone. Thank you for joining us at the H.C. Wainwright 28th Annual Global Investment Conference. My name is Emily Bodnar, and I am an Equity Research Analyst at H.C. Wainwright. I will be doing a fireside chat with Jeet Mahal, Chief Executive Officer of Jasper Therapeutics. Maybe to start, we can go through the recent merger with Kira Pharmaceuticals, maybe discuss what assets were involved with the merger, and where the combined pipeline stands today.
Sure. Thanks, Emily, and thank you for inviting us to join you today. Yes. Recently, Jasper and Kira Pharmaceuticals announced a sign-and-close merger in mid-July of this year. We are pretty excited that this now creates a company with multiple assets in immunology, two of which are in the clinic, and a third one that is close behind. Our lead asset, known as KP-104 or vensobafusp, is a dual-functional inhibitor of the complement cascade. It inhibits both the alternative and terminal parts of the complement cascade, so we think it has a very unique mechanism of action. Kira has published positive phase II data in PNH over the last few years. The lead indication there in PNH, we are looking forward to talking to the FDA next year at the end of phase II meeting about a potential approval pathway.
Furthermore, we have started a renal basket study led by patients with IgA nephropathy, looking to release the first interim data from that study later this year, and then expanding the basket study to include patients with C3G, FSGS, and possibly a few other renal indications as well. We think that the kidney undergoes different types of injury, but complement seems to be a common pathway for many of them. Our second asset, briquilimab, is an aglycosylated IgG1 antibody against the KIT receptor. Previously, we have developed that for mast cell diseases as well as a conditioning agent for patients undergoing stem cell transplantation in a variety of indications. Right now, we are completing some of the work we had agreed with the FDA regarding a potential pathway to approval for patients with SCID, severe combined immunodeficiencies, undergoing re-transplant.
We look to have the analysis done later this year and go to the FDA for a pre-BLA meeting next year, with the potential for a BLA at the end of next year. In SCID for transplant, briquilimab has both orphan and rare pediatric disease designations, so we would expect to be eligible for a priority review voucher if approved. We have also completed a phase II study in a key mast cell indication called chronic spontaneous urticaria. That was a great proof of concept. We think that this is a large market, with further potential to develop briquilimab as a chronic agent. However, with the new company and the different programs that we have and the amount of capital and the competitive landscape in CSU, we have not committed to further development there.
But we will continue to assess the landscape and what we think is a potential large opportunity for briquilimab. The third asset, I am so excited to have so many different assets right now. We have quite a development team, too. The third asset, KP-701, is a bifunctional antibody or a bispecific antibody that targets both CD79B and CD32B. CD79B, of course, part of the B cell receptor. CD32B is the FC inhibitory receptor. So by bringing those together, we think we can induce anergy in B cells. We know B cells are really important for a lot of autoantibody diseases, and we have seen great success with depletion programs like Rituxan. But really, for a lot of chronic patients who are on these agents for decades, that comes at a pretty significant cost of immune suppression, long-term immune suppression.
Even if you come off an agent like Rituxan, you are talking months and months and months before your B cell compartment starts to normalize. With this approach, we think that we can provide that type of efficacy that has already been proven by B cell targeting agents, but with a potential for improved safety profile, because again, the B cells are there, they are just more or less put to sleep. So those are the main assets. There are a few others. One of the assets, C5 long-acting program, has been out-licensed to Mirador also as part of this transaction as well, and we do have additional assets deeper in the pipeline.
Perfect. As you mentioned, KP-104 is a bifunctional biologic. So maybe walk us through the various approaches of targeting complement pathways, and what is the benefit of the dual targeting?
Yeah. So vensobafusp, KP-104, very unique molecule, we think, in the field of complement. On one end, it is an antibody target C5, similar to Soliris or ULTOMIRIS. We know that targeting C5 will disrupt the memory and attack complex. So it really is the most important step of protection with regards to analytic indications like PNH, but also what we think leads to the damage in the glomeruli. On the other end of the molecule are the actual functional domains of Factor H. So Factor H is a part of the complement cascade that provides regulation on the alternative side. So it is more like modulation, where we can basically fully block the C5 component of the complement cascade on the cell surface, be it a red blood cell or in the glomeruli, and then further enhance the activity with Factor H.
What that brings is the benefits of the upstream inhibition pathways such as Fabhalta, of course, Factor B inhibitor, that allows restoration of hemoglobin in PNH patients. That is the big difference between Soliris, ULTOMIRIS and Fabhalta for PNH patients. We know that Soliris and ULTOMIRIS protect the patients, but you are still transfusion-dependent for a lot of them because we do not see normalization of hemoglobin, but with Fabhalta, you see that normalization of hemoglobin, but you do not have the protection for the breakthrough if that occurs. With vensobafusp, you have both, and we think that is pretty unique for a disease like PNH. In the kidney space, again, we think this is a way to go directly at the complement that is already activated and sits in the kidneys with the C5 component, but also have the disease control ability from the alternative pathway.
We are pretty excited to see what the data shows in our renal study. We think that these mechanisms may be synergistic or additive, but we will have to see.
Perfect. That kind of leads into my next question. You mentioned you had positive phase II data in PNH. Maybe discuss the data a bit further in detail, and then how that compared to other competitor complement inhibitor programs.
Yeah, sure. The PNH phase II is 18 patients, kind of a very strong first step in the development of that indication, where we saw 100% of the patients, all patients got at least a 2 g /dL increase in hemoglobin. 89% of patients restored to normal hemoglobin levels. We think that is early, but indicative of potentially best-in-disease kind of profile. 100% of the patients remain transfusion-free. 94% of the patients had an LDH of below 1.5 upper limit of normal. We do think that data set shows the potential of this dual mechanism of action, where we are seeing everything we would want to see from the molecule in terms of both alternative and terminal inhibition.
Perfect. What are you looking for in terms of design of the phase III trial with your upcoming discussions with the FDA, and what does timing look like for getting that initiated?
We're looking to have our end-of-phase II meeting sometime in the first half of next year. We're completing the CSR study reports for the PNH study and want to make sure that we really nail what's next. The design of the phase III or the phase III trials we think is fairly well set at this point with regards to approval pathways, where we're seeing one study in naive and one study in C5a-experienced or switch patients. That's probably where we would start with the FDA, but we could also understand if the FDA is maybe moved off a little bit. These aren't very large studies. We think we have the development capability to do these studies through their approval.
As we kind of discussed, there are other therapies already available for PNH, so how do you view the current landscape now, and what does the market opportunity look like for a newer agent coming in?
Well, what we believe we've seen is growth in the market. I think if you really rewind the tape, folks are still pretty surprised at how successful Soliris was versus the initial estimates. Now we've seen with multiple agents being approved that there are still growth opportunities around the world for complement inhibitors. In terms of the positioning, again, we'll have to see what our data shows in the next set of studies. If the data holds, we think that this is the only molecule, again, with that bifunctional component, where we're talking about controlling both alternative and terminal pathways. For example, with Fabhalta, very important drug, more convenient oral BID than the C5 inhibitors. But risk of breakthrough. That's a pretty significant risk because that really is the primary goal of treatment, is to protect patients from the breakthrough, the PNH events.
We do think that a number of patients and physicians may want that added benefit, that added efficacy or protection, at least from a Factor B inhibitor. But then compared to the C5 programs, the benefit of remaining transfusion-free is also very meaningful. We do think that there's really a potential to position this as an incredible agent for those patients. Maybe will depend on particular physicians or physician groups in terms of how they use it with the existing agents.
Yep. You mentioned you have the phase II basket trial ongoing in several renal indications, and you've guided to initial data in the fourth quarter. What are your expectations for that initial data readout, and how many patients worth are we looking at?
The first part of the basket study is in patients with IgA nephropathy, so about 18 will be part of this first analysis. Really, that's allowing us to get a quick proof of concept in renal diseases. From there, we would expand to a larger subset of patients with IgA nephropathy, as well as add cohorts for C3G, FSGS, and potentially others. Really what we're looking for at this first stage is that proof concept, a little bit of guiding on dosing as well. Looking at the history of other programs and development in this space, it seems to be that the amount of disease burden or molecular burden we see in the renal space is a little bit less than PNH. We think that Q4 or Q8 week dosing is even possible in the renal patients.
That's another piece of key information that we want to gain in this first stage. We're pretty excited to see this first stage, but also that'll allow us to get the investigator momentum interest in expanding to these other disease areas as well.
Yeah. I think given the small cohort of patients, how do you get confident in the profile of KP-104 to support continued development in these larger indications like IgA nephropathy, or is that something you're looking at as more of a proof of concept indication?
Well, I think IgA nephropathy is interesting. We know that many of those patients are autoantibody driven. We see the success of the BAFF/APRILs, for example, or some other mechanisms that target specific autoantibody production. We don't think that's the case, or at least anywhere near the percentage of patients that are autoantibody driven in these other renal indications. So on one hand, IgAN allows us to move into the renal space quickly, with some key metrics that we know we can benchmark against Soliris, Fabhalta, even the BAFF/APRILs. In terms of future development there, we'll see, based on the data that we're generating right now, plus the stage two. So, it'll have to be a competitive profile for us to really continue long-term to go after IgA nephropathy patients. But we do think that has significant potential.
Again, we've seen the C5s and the Factor Bs do quite well in IgAN patients with regards to proteinuria. We think that if those mechanisms are additive or synergistic, we might see something on the order of the BAFF/APRILs, or even better. So we're waiting to see.
What other indications do you potentially view as high priority for KP-104? Following the stage one data later this year, what could the stage two portion of the trial look like?
Yeah. There's a lot of potential across a few different indications in the kidney space. I think if you look at the development of other agents, we could see a handful of those be high interest. I don't think we want to commit to that right now. It is something that we're assessing, and it is something we want to give more guidance to before the end of the year.
Then you talked briefly about KP-701 earlier. How do the targets differ from the traditional B-cell targets, like CD19, CD20?
Yeah. CD19 expressed pretty early in B-cell development. CD79B, of course, part of the B-cell receptor complex, so it really mirrors when the B-cell receptor is brought to the cell surface. The B-cell receptor is a little more in terms of not early B-cell maturation, of course, when they're not even specific for an antigen, but pretty early, right? And up until plasmablast stage. So that is, I think, an important part in terms of targeting these autoantibody diseases, where we still allow for B-cell maturation to a certain point before turning it off. The important part there is if you do have a reason to come off therapy, there is an early group of B-cells that are available for maturation. So that's the big difference, I think, between CD19 and CD79B, is that early stage of cohort or B-cell cohorts which are mature or not mature.
We think 701 might have some other benefits as well, based on our early assessment of PK and the preclinical data. We think that this is potentially a monthly injection.
Okay. Where are you in development with KP-701? What are the next steps for that program, and are there any clinical stage benchmarks that you are looking at currently?
Yeah. So pretty close to filing a CTA or IND. That is really one of our goals here towards the first part of next year. In terms of benchmarking, we do know that there is another CD79BxCD32B agent in phase III, and also has already produced pretty good data in IgG4 disease. So we do think that there is potential to follow the development path of a few others. But in terms of the larger potential for that molecule, we will have to see. Obviously, that is a much smaller indication than the autoantibody indications that we see being developed for B-cell depleting agents, right? So we do think that showing proof of concept possibly in an indication where there is a clear benchmark and a good open path to discovery in terms of the development pathway would give us the first road, and then we will see from there.
There should be a lot of potential for an agent like 701.
You mentioned a bit about briquilimab in your opening lines. Do you still see a path for development in CSU for briquilimab, and if so, what is that contingent on?
Yeah. Pretty exciting, CSU, obviously large indication, large chronic indication, dermatology, allergist based. We have seen some recent approvals with RHAPSIDO from Novartis and DUPIXENT from Sanofi. We know that the team at Celldex is developing barzolvolimab for CSU as well. We are awaiting their phase III data, which should be coming out pretty soon. I think we want to see that data, of course, as a key benchmark, as another aglycosylated KIT inhibitor. What their data shows in terms of complete response rate, which is really the measure of success here, I think, in this disease. Patients, this is a pretty burdensome disease from an itch and appearance standpoint, and patients really want that cleared.
We do think that CRs are the benchmark in CSU, but with the difference between briquilimab and barzolvolimab, the unwanted effects, especially on skin and hair we see with barzolvolimab, if we see that in the phase III program, that might be a key differentiator for briquilimab. So, we are not committing to that development, but we could see how it goes in terms of the phase III results from barzolvolimab. We think that RHAPSIDO launch is going well. But again, we now have vensobafusp and KP-701 to develop as well. And we will see what the best use of capital and development team time is across the portfolio.
Talk to us about where you are with the Kira merger completion and your expected cash following that merger completion.
Yeah. So I will start with the cash. So as part of the sign and close, the PIPE, about $132 million, along with an out-license to Mirador Therapeutics with an additional $12 million. So, about $140 million total, which takes the company well-funded into late 2028. In terms of the steps of the merger, technically the merger is closed, and that is part of the sign and close process. However, we are still working on shareholder conversion of the preferred to common, which requires a shareholder vote, and so that will be held in early November. And at that point, I think we will be moving forward completely as a single company.
Perfect. To close out, walk us through some of your key upcoming catalysts and milestones that investors should be looking out for in the next 12 months.
Yeah, quite a few. In terms of data that Kira Jasper is generating, this year we'll have, as we said, vensobafusp proof of concept data in IgA nephropathy. We'll have the first analysis of briquilimab in SCID patients against an external control. Moving into next year, we'll have additional data from vensobafusp in additional renal indications, C3G, FSGS, a larger set of IgA nephropathy patients. We'll have the first data coming from the 701 program. We'll have potential FDA feedback on briquilimab, and hopefully FDA feedback on the PNH pathway for vensobafusp as well. So, that's a lot for the next 12 months, and we're pretty excited about it.
Awesome. Thank you so much, Jeet. Thanks everyone who's been listening in. Hope everyone has a great rest of their day.
Thanks, Emily.