Conference Transcript - NKTX 2026-06-30

Emily Botner, Analyst — H.C. Wainwright

Good afternoon, everyone, and thank you for joining our H.C. Wainwright fourth annual virtual cell therapy conference. My name is Emily Botner, and I'm an equity research analyst at H.C. Wainwright. I'm pleased to introduce Nadir Mahmood, who is the president of NCARTA Therapeutics. Maybe to start, for those who are newer to NCARTA, Nadir, if you can give us a bit of an intro to your allogeneic CAR and K cell therapy platform and some of

Nadir Mahmood, Other

your ongoing programs with NKX19. Great. Well, thanks so much for having me today. And apologies for a little bit of a late start here. So NCARDA is an autoimmune disease company. We are developing a lead program, which is a CD19-directed CAR NK cell, a natural killer cell that is engineered to express a CAR chimeric antigen receptor against CD19, and also engineered to express a membrane-bound IL-15 to enhance persistence in a variety of B-cell-mediated autoimmune diseases. And so we're particularly excited about this program and the profile of a CAR-NK given the targeting, but also the unique safety profile that exists with NK cells that we believe really allows us to unlock the full potential of this type of approach in an autoimmune disease setting. So we currently have two company-sponsored INDs. The first one, Entrust One, is in our nephrology indications, lupus nephritis, and primary membranous nephropathy. And then ENTRUS2 is a basket trial looking at systemic sclerosis, myositis, ankyosciative vasculitis. And recently, we just added our rheumatoid arthritis to that as well. And then we've got a couple of investigative-sponsored trials as well. One is in systemic lupus, and then the other one is and myasthenia gravis. So really for us, the concept and idea here is building on the data that everybody's familiar with from Georg Schett at Erlangen and what we've now been seeing from a number of other companies using B-cell depletion strategies is to really try and what we believe is find the sweet spot of where NK cells fit within this paradigm, which is can we deliver potentially the transformative potential of cell therapy, like what we've seen from autologous CAR-T with these incredible, you know, immune resets that lead to long-term drug-free remission with a more safer and more convenient therapy that allows broader accessibility to the larger patient population that faces these diseases. So really trying to get out there in the community setting. And that's where we believe NK cells, because we don't see cytokine release syndrome or in your neurotic neurotoxicities, really have a safety profile that is unique that allows us to be able to do that. Yeah, maybe going along with that,

Emily Botner, Analyst — H.C. Wainwright

obviously, as you mentioned, majority of the data we've seen in the autoimmune disease space has been with autologous CAR-T therapy. As an allogeneic CAR and K therapy, how do you kind of think that this may be a better suited type of therapy for autoimmune diseases, where obviously patients have more chronic disease compared to the oncology settings?

Nadir Mahmood, Other

Yeah, I think there's, you know, a really interesting feature that emerged from the very initial data published by Georg Shett and his colleagues, which was really demonstrating that the B cell killing and that immune reset that occurs following that actually doesn't require this prolonged depletion and killing of B cells. That really that B cell burden needs to be taken down and depleted early on in the first, say, three to four weeks. And you don't need sort of this continuous expansion of a population that then targets and kills this ongoing larger population of B cells like you have in a tumor setting, for example. So we believe that observation really ties nicely with one of the key features of NK cells, which is they're not a very persistent cell type. When you put an NK cell in, it's going to last for a few weeks, kind of do its job, and then it goes away. And that's where we believe in an autoimmune disease setting where that risk benefit ratio is really different than in an oncology setting and you've got and you're typically used to giving you know immunosuppressive therapies or glucocorticoids for example that this really presents an opportunity to have something that can come in drive that deep b-cell depletion trigger that immune reset and give you these responses without having to deal with sort of potential long-term toxicity or even near-term toxicity because the NK cells won't expand in vivo. So when you have that biological, that fundamental difference in the biology of how NK cells work versus T cells, you're not going to see those side effects like CRS, ICANs that you typically see with T cells because the biology is just different. But if we can drive that B cell depletion the way that we believe we can, then, and you can trigger that immune reset, then we believe you have a therapy that could lead to longer term durable remissions. But then the other added benefit and something that FDA has given us green light to do now is you can redose these therapies, right? So if a patient is able to get into remission for a certain period of time, call it, you know, several months, a year, a couple of years, and then they're relapsed or they're starting to flare, there's an opportunity to go back and give them this therapy again because it's safe, because it can be administered in an outpatient setting, there's a lot of opportunity there where we believe as you tackle some of these chronic indications in autoimmune disease, the NK cell approach really does a nice job sort of marrying that, you know, the benefit of a cell therapy, but with the convenience of what looks like more of a traditional biologic,

Emily Botner, Analyst — H.C. Wainwright

but with a really clean safety profile to date. Yeah, makes sense. Can you discuss some of the translational work that you've done and the results you're seeing in terms of B-cell depletion and how that kind of compares to what you would expect to see with some of the

Nadir Mahmood, Other

Talgos CAR-T trials? Yeah, so the translational work that we're doing sort of is what you've seen from a lot of folks where, you know, we're going to look at peripheral B-cell kinetics. We're looking at BATH elevation also as it's a surrogate for tissue depletion. And then, of course, we're going to look to see what the reconstitution of B-cells is following depletion. So, can we get naive B-cell population indicative of a true immune reset. The other thing translationally that we're doing also is we're looking at tissues and lymph nodes. So I think the peripheral B-cells are a nice indicator that you're getting depletion, but ultimately the action is happening in the lymph and in the tissues, right? That is where we're seeing these pathogenic autoantibodies driving inflammation and damaging tissue. And so what we want to be able to see is, okay, we can get the peripheral B cells down, but what are we doing to actually get to the sites of action? And can our cells get there and deplete B cells? So that's part of the data that we're generating. When we give our update this year, we will be sharing whatever data we have there. So I think those are sort of how we're thinking about translational. And, you know, one more point on that is when we started this trial, we were using only cyclophosphamide as the only conditioning agent, but we've since moved over to a more robust conditioning with fludarabine and cyclophosphamide, and the reason is because we see more deeper B-cell depletion when you have fludarabine and cyclophosphamide. And we believe that is part of the regimen that can drive us to depleting enough of the peripheral B-cell sync so that the NK cells themselves can get to the tissues and lymph nodes and do the activity there. And that also is probably closest to what Dr. Shett has demonstrated in his autologous CAR-T work using fludarabine and cyclophosphamide.

Emily Botner, Analyst — H.C. Wainwright

Yeah. Maybe moving to UNTRUST-1, which is the lupus nephritis trial that you discussed, maybe talk a bit more about the trial design there, where you kind of are in development in that trial, and what some of the kind of key endpoints are for efficacy.

Nadir Mahmood, Other

Yeah. So lupus nephritis, like this is an important B-cell-driven kidney disease where standard of care is really chronic immunosuppression. So there's an incredible need for a more durable intervention. So what we're looking at are sort of your traditional renal responses as sort of the primary efficacy lens. So there'll be complete renal response, partial renal response rates, proteinuria, complement, anti-double-stranded DNA. And so these are end points that, you know, the field recognizes and FDA has accepted in other programs. And now that we're fully outpatient and we can go with 4 billion cells per dose given three times for total of 12 billion cells with only a two-hour observation window, you know, I think it really gives us the opportunity to access a much broader population of lupus nephritis patients who are out there, you know, who can't always come into the large medical centers in the big cities to be seen and sort of put their lives on hold, especially, you know, when nephritis flares are being managed with immunosuppressives or corticosteroids. So those are sort of the primary efficacy endpoints we're looking at. And then we're also, as I mentioned earlier, on the translational side, we're going to be looking at B-cell kinetics, BAF signaling,

Emily Botner, Analyst — H.C. Wainwright

reconstitution of naive B-cells. Yep. Are there any, I guess, numbers in terms of complete renal response that you're kind of looking to see to get comfortable with maybe

Nadir Mahmood, Other

moving that indication forward? Yeah, I think given this patient population really doesn't have much in terms of standard of care, and you look at what some of the other companies in the cell therapy space have reported, which are really to date pretty small data sets. I think, you know, I think one study has about eight or nine, and others got about six. So, you know, what the bar is exactly probably trying to drive meaningful remission that is durable. I think it's a little early to sort of say kind of exactly what that bar is going to be, but certainly something we're going to continue tracking as more data emerges so we can start to sort of set expectations for ourselves as well for the street sort of as to what that looks like. But really, I think we do want to see complete Reno responses and see that there's durability there at least several months, potentially longer. And with the ability to retreat, we might have some examples where we could potentially put folks back into remission if we have that opportunity. Yeah, maybe on that

Emily Botner, Analyst — H.C. Wainwright

point, we did have a question come in about kind of navigating reimbursement with potential redosing. I don't know if that's something you've thought about at all. Yeah, I mean, it's something

Nadir Mahmood, Other

still early in terms of how we're assessing things. I think that the redosing provides an opportunity for flexibility in terms of how you can approach what the overall commercial sort of approach and strategy looks like. I think we do believe and we are confident that in the most cases, a single cycle of cells with the three doses given over the course of a week should be sufficient to drive, in our opinion, hopefully long-term durable remissions. And so we sort of see the the redosing more as sort of a an opportunity to create some additional flexibility for either patients that maybe got close and didn't quite get there or that can you know have an opportunity to be retreated but we it's not we're not looking at it sort of as a chronic we're going to give this you know every couple of months sort of approach there so I think that's something we're going to look at but right now we're sort of still focused on okay what does the original cycle look like in terms of what market access and reimbursement could be.

Emily Botner, Analyst — H.C. Wainwright

Yeah, makes sense. On the NTRUST2 trial, you mentioned, obviously, it's a basket trial with several indications. I think RA is obviously an interesting one. We've seen some NK cell competitor data this year in that setting. Maybe talk to us a bit more about why you're excited about RA and how you think NKX19 as an engineered cell therapy can maybe differentiate.

Nadir Mahmood, Other

Yeah. So RA is an indication that we actually didn't originally have in the trial. It's something we added more recently, and that was really based on feedback from some of our investigators. And as I think data has emerged from some of our competitors, Artiva had some really nice data at ULAR that they presented with a 71% ACR 50 at six months in a refractory population. So I think seeing a signal like that and the opportunity that's there, but still with a differentiated product relative to our competitors. I think that was something that our investigators like, you've got to get this into patients. You know, we want to support evaluating this in our RA. So I think scientifically as well, there's a lot of rationale around CD19 and targeting by that. And I think the big difference sort of in our approach versus competitors' approach there is the fact that this isn't a combination that we're utilizing. There isn't a monoclonal antibody that we're co-administering to drive responses. For us, it's really an engineered cell targeting CD19, which we believe in these B-cell-mediated autoimmune diseases, including RA, is the primary antigen that represents the lineage of these autoantibody-producing B-cells. And so we think with the engineering and a simpler trial design, simpler regimen, there's an incredible opportunity to, you know, potentially get some really strong responses, maybe in line with what our competitors saw. But we think, you know, would that combine with the convenience and also continue to be outpatient in that setting, that there's an incredible opportunity in this population. Because if you look historically, I mean, the response rates have been, even with rituximab alone, have been abysmal. So I think there's a lot of room and I think a lot of opportunity to show that there's something truly meaningful for this patient population that can drive these durable responses. And so this is an indication that was just recently added. So we're still kind of in the early days in terms of enrollment and treatment of patients relative to the other indications

Emily Botner, Analyst — H.C. Wainwright

and interest too. Yeah. Maybe to talk more about the data update that you're planning for this year, what should we be expecting in terms of what you might share for interest one and interest two? Obviously, you have different indications as we've discussed. So how might that look?

Nadir Mahmood, Other

Yeah, I think given that this is going to be our first data update for the autoimmune program, I think that one of the fundamental things we want to do is basically provide an update kind of across the board what we're seeing in both interest one and interest two patients treated to date. Now, I think it's going to be important to understand and what we're going to try and communicate is, you know, there's a couple of things. One is we started early on with cyclophosphamide only as lymphodepletion, and now we have cyclophosphamide and fludarabine, which is the regimen that we are confident in, in terms of moving forward. And so we're going to share what we had from cyclophosphamide only, but really our focus is going to be on those patients treated who were pre-treated and conditioned with flu and psi. The next part is, unlike a T cell, you have to do a real dose escalation for an NK cell therapy. So we started with 1 billion cells per dose times 3, then we moved to 2 billion, and now we're at 4 billion. And so it was only earlier this year that we started the 4 billion. And so what we want to really focus our update around is what is that regimen and dose that we're going to take forward and how do the responses at that dose with fludiarabine cyclophosphamide inform what our next steps in clinical development are. So we'll share all the efficacy, response data, any translational data, because we understand and we believe, too, that, you know, demonstrating that you're getting a mechanistic effect here that's driving the responses, especially, you know, for some of these patients who are dosed more recently, we're not going to have that much longitudinal data. And so the way you sort of bridge and get confidence in the durability is saying, we're seeing strong early responses. And with that, we're seeing translational data that suggests that we're driving an immune reset. So ideally, we want to be able to put data together in a way that we can convey all of that, but also very clearly articulate which particular indications and what doses we are moving forward.

Emily Botner, Analyst — H.C. Wainwright

Yeah. Is that something that you're planning to do with this update, kind of disclosing go-forward dosing and go-forward indications, or would that be a later topic?

Nadir Mahmood, Other

Ideally, that is part of what we'd like to update, is really sort of, you know, not just here's the data, but here's the data, and here are next steps in clinical development and sort of where we want to go forward with the program. So to the extent that we will have any, you know, FDA regulatory conversations and have guidance on sort of what the path forward looks like, you know, we'd be happy and wanting to share that information and that update as well.

Emily Botner, Analyst — H.C. Wainwright

Yeah, I think as we've seen some kind of pivotal trials in the space emerging, majority of companies have kind of done single arm, fairly small trials. Do you think that that's probably the same path that you'll be taking as well?

Nadir Mahmood, Other

Most likely, I mean, that's, I think, the really exciting opportunity here that FDA has demonstrated through now, you know, a few companies that, unlike other modalities and historically in these autoimmune diseases, we are now seeing multiple examples of single arm trials. You know, and relatively manageable trials when it is a, you know, a randomized control trial in the context of, like, comparing cells plus rituximab to rituximab alone. But given that we've got the engineering and if we can demonstrate, you know, strong efficacy with some early durability, then I think we do have an opportunity here to potentially accelerate development by moving into some single-arm trials. And the FDA has told us, as they've told other companies, like when you're at that point and you're ready to have that conversation, like we're ready to have that meeting with you. So I think the door and the opportunity is there for us.

Emily Botner, Analyst — H.C. Wainwright

Yeah, makes sense. I guess for durability, what would you kind of like to see longer term, maybe next year as you kind of have more data to read out? And how do you think that might differ for an allogeneic approach relative to like a tall guest therapies?

Nadir Mahmood, Other

Yeah, I think when you have something that has this really unique safety profile, like a car NK does, and the ability to redose, and we can manufacture this at scale, I think the logistical parts and accessibility really lend themselves to this idea of redosing. And so for us, like I mentioned before, it's not sort of like this is going to be something that patients, we expect patients to be taken like every couple of months. But I think we want to see at least several months of durability before we get to redosing, you know, potentially 12 plus months, something like that, I think would be an interesting target for us to look at. But as the data emerges and we continue to have conversations with the rheumatology community sort of around some of those aspects, I think there's definitely opportunity. I mean, we're already seeing opportunities to re-dose and potentially drive deeper responses with more durability with some of the patients that got our earlier doses. So, you know, we'll be providing some interesting updates around that too.

Emily Botner, Analyst — H.C. Wainwright

So maybe to end, if you can kind of go through a summary of kind of what we should be looking out for for the next 12 to 18 months.

Nadir Mahmood, Other

Yeah, I mean, really the big catalyst for us is the data readout in 2026. So everything we're doing right now is 100% execution focused and focused on trying to make sure we provide a robust and meaningful update, where it's not, you know, a couple of patients here, a couple of patients there, but, you know, a meaningful number of patients with sufficient follow up that we can actually say that we've, at least in the indications that we're focused on, that we can say we've got something here in terms of a program, and this is what the next steps look like. So really, any updates or anything else we do over, you know, the remainder of 2026 is going to be geared towards that. And then as we get into 2027, you know, depending on what we talk about at the data readout, you know, hopefully it provides opportunity to really take the next step in terms of clinical development and move this program forward. So really, I think that's kind where we're headed i think that's what people really have their eyes right now on is our 2026 update so we're excited to provide that soon enough yeah definitely i think we're very excited

Emily Botner, Analyst — H.C. Wainwright

for that as well thank you so much nadir thanks everyone who's been listening and have a great

Nadir Mahmood, Other

rest of your day all right thanks emily