Okay, great. Good morning everyone, and thank you so much for joining us at TD Cowen's 46th Annual Healthcare Conference. My name is Sarah Cai, and on behalf of the TD Cowen Biotech team, it's my pleasure to introduce Paul Hastings, CEO of Nkarta, and Nadir Mahmood, President of Nkarta. We have a bit of a special surprise for everyone today, as Paul and Nadir are going to do a novel fireside format where they'll start by interviewing each other. We'll have them take it away, and then we'll reserve some time at the end for Q&A. Without further ado, Paul and Nadir. Yeah. It's not that we wanted to steal it from you. We were told we didn't have an analyst to come with us, so we decided to do our own fireside chat. Right. Okay. All right. Take it away. Thanks for having us. Maybe to get us started, Paul, would you like to give a overview of the company and a little bit of background? Sure. We are an autoimmune company discovering and developing natural killer cells. We have two clinical trials right now, which is our laser focus, Ntrust-1 and Ntrust-2. Ntrust-1 is looking at CD19 targeted, allogeneic off-the-shelf natural killer cells, in lupus nephritis. Ntrust-2 is a basket study which is looking at that same CD19 targeted allogeneic NK cell therapy in scleroderma, myositis, vasculitis. We have 2 ISTs. One is in systemic lupus erythematosus, and the other one is in myasthenia gravis. We're hoping by the middle of this year to update everybody on the data we have from the both of these studies to look for proof of concept to go to the next step in development, which is really moving into pivotal trials. All right. You wanna talk a little bit about the advantages, benefits of NK cell approaches versus others? Sure. Is there anything you wanna add to the introduction, if I missed anything, or did I get it all? No, I think those are the key points. Yeah. Advantages to natural killer cells. Accessibility is number one. These cells are available. They're off the shelf. Patients don't have to go through apheresis to get their cells. The cells are on demand. In terms of accessibility, we've seen no cytokine release syndrome, no neurotoxicity in any of the patients we've treated. Some minor toxicities in our oncology studies, but in our autoimmune discussions or in our autoimmune style trials, nothing. Safety, accessibility are the keys to these cells being able to administer them in an outpatient setting. The short-lived effect of these cells are, in our opinion, handmade for autoimmune disease because you want immediate B-cell depletion and reset to normal B cells. Yep. I would say just add to that we aren't in the outpatient setting just yet, but we were in oncology, and so we're confident that with the safety profile of the CAR-NK approach, we should be able to move into an outpatient setting in the autoimmune disease setting as well. Right. Which is where we'll end up, when we commercialize this product. Right. Yeah. Totally. Totally in community centers where the patients are. Yeah, exactly. It's, it's about going broader to a much larger patient population beyond the specialist cell therapy centers where the oncologist, who's a cell therapist, has to work closely with the rheumatologist. We wanna make that something that a rheumatologist can administer at their site, at their clinic, and not just in the big cities, but out in the rural communities and places where patients don't have to travel that far and, you know, upend their lives for several weeks just to get the treatment. Right. With that, maybe you can give an update on the clinical program and how that feeds into what you just said. Yeah. Just to reiterate, you know, we've got the two INDs, Ntrust-1 and Ntrust-2. The first one is in the kidney space with lupus nephritis, primary membranous nephropathy. The Ntrust-2 is the basket study, systemic sclerosis, myositis, vasculitis. We've been enrolling across both studies. We think one of our last updates we had started dose escalation, moving from our initial dose of 1 billion 0, 1 billion day three, and then day seven. Total of 3 billion cells cumulatively across the dosing. Now we had moved up to 2 billion, was sort of where we were at last update that we gave. You know, we feel confident we can continue to escalate as the safety profile continues to emerge, and we generate more data. If we need to go to higher doses, we think NK cells are primed for a situation where you have a large therapeutic window to leverage the safety profile to try and get as many cells in as possible. You wanna talk about the next dose level, what that is? The next dose level will be 4 billion cells given 3x. Per dose. Is what we're planning per dose. $12 billion total. Exactly. 12 billion total cells over the course of that which we think could be really interesting and compelling, especially when you look at sort of where autologous CAR-Ts are dosing and what that in vivo expansion cell number looks like. This might be something kind of closer to that. We've seen that from some other studies as well, that they would go up to 4.5 billion cells given multiple times. Other NK studies. Other NK studies. Yep. Sorry. Yeah. I think that's the interesting thing, just a nuance to point out there is unlike a T-cell which expands after you administer it in vivo, so you give a subtherapeutic dose- Mm-hmm You get to that therapeutic dose through an in vivo expansion. An NK cell does not expand or has a very limited in vivo expansion. What you're actually administering is the therapeutic dose, and over time, that dose will reduce and decrease. We've found through our phase I and then also from our oncology experience that trying to pack in those multiple doses within a shorter timeframe of that week. Mm-hmm Gives us the best probability of trying to maximize the number of cells that can be there to kill the target cells. Did you want to add anything on the dosing regimen? Yep. I think that's the key point is, so we start with lymphodepletion. Mm-hmm. Your standard fludarabine, cyclophosphamide lymphodepletion. Mm-hmm. Then we give the cells, day zero, day three, and day seven. That's the dosing regimen, dosing paradigm. We- Do you want to talk... Sorry. Sorry. Just quick follow-up is the LD regimen is going to be Flu/Cy, right? That's correct. Yep. You've now converged on that, like harmonized across both trials? Yes. Okay. Great. Yeah. That kind of feeds into the next question, right? Yeah. You want to talk about sort of, lymphodepletion, sort of B-cell depletion, what we're thinking there? Right. You mentioned Flu/Cy versus Cy. Mm-hmm. We originally started using cy alone, thinking that the rheumatologist would appreciate not having to use fludarabine in the population of autoimmune patients who are primarily women- Mm-hmm And primarily living in rural communities and you know, and so a lot of complications. All the other, CAR-Ts and even the CAR-NKs were using a full lymphodepletion. We noticed that with Cy alone, we weren't quite getting the lymphodepletion we wanted to. We weren't quite getting the B-cell depletion that we wanted to see. Mm-hmm. With Flu/Cy, virtually all the patients have full B-cell depletion. Lymphodepletion is important in this population. The safeguards using it, one must be diligent about and provide those services for the patients if they want them. Challenge other companies, particularly when for the women. Mm-hmm. Fertility services, etc., if they want, if they want those. What we've discovered is that the rheumatologists are now getting used to working with the cell and even on using fludarabine and cyclophosphamide. Okay To get this complete. What you really want is you want to get the knockdown of these B cells, the bad B cells, all the way down to zero, you're going to get that with fludarabine and cyclophosphamide. Then you want the cells to do their thing. Right And reset, the NK cells to do their thing and reset the B cells. Thanks. Yep. Is it my turn to ask you? Yeah. Oh, this is, yeah, this one is, this is my favorite topic. Mm-hmm. Other companies are actually looking at reduced lymphodepletion regimens, and we've increased it. Why do you think that is? Yeah. I think it's interesting. There definitely is this sort of trend with a few companies now to try this modified or reduced lymphodepletion. Now, as Paul mentioned, this is something we sort of pioneered when we first kicked off this program, but you know, we generated data that suggested that you needed the complete B-cell depletion, and that's really achieved with fludarabine and cyclophosphamide. Mm-hmm. We're seeing some companies, these are T cells, where they are either using a modified, meaning it's either cyclophosphamide or bendamustine, no fludarabine. Okay. What you see there is incomplete depletion, meaning maybe on average 75%, 80%. We're also starting to see relapses and other therapies having to come in to rescue patients after a few months. Mm-hmm. It's, you know, these aren't huge numbers that have been reported yet, but there's a few. You definitely, you can see that there probably is a trend there towards maybe not as robust durability as what we've seen sort of, say, from Schett or from others who have done the full Flu/Cy with autologous CAR-T. Then there's also examples, just a handful now, of no lymphodepletion at all. Okay. In those patients, at least from one of the studies we've seen, you know, they were getting maybe 40%, 50% on average depletion. I think the thought there is probably limited durability expected. Okay. I think there's one study where there's about three patients that were with pemphigus vulgaris. Mm-hmm who got no lymphodepletion, and they actually had pretty good B-cell depletion. Mm-hmm You know, it's certainly, I think, viable that there's probably some indications or some use cases where it probably makes sense and it can work. Yeah. I think for sort of a broader therapy, there's gonna be probably the need for true deep B-cell depletion. I think that's what we've seen when you look at the larger data sets, like a Chet, public 30+ patients, multiple, you know, pretty much all of them in complete remission, durability out several years now. I think one of the key sort of predictors of that drug-free remission is the deep B-cell depletion and then the immune reset of the naive B cells coming back. Mm-hmm. I think that's the early signal to give you confidence that what you're gonna see is a durable long-term remission. Totally. I think if you don't see that upfront, I think the expectation has to change as to sort of what that durability looks like. Mm-hmm. Data will eventually answer the question for us over time. You know, I guess it comes down to, like, are you really looking for something transformative as a therapy? Mm-hmm Or just another tool in the toolbox. Right Similar to many of the agents that we already have? What is the value proposition of going through the logistics and the challenges of an autologous product- Right ...in that setting? One and done. Yeah. Another way to look at this is maybe less severe disease requires less lymphodepletion. Mm-hmm. Maybe as we progress down the clinical path here, in earlier stage disease, you may not need as much lymphodepletion. Okay. We sort of started the trend early on thinking that was the way to go. Right. I think people started following us down that path, and then we went this path. I think people will end up here in the setting of these phase I, II trials where you're looking at two courses of immunotherapy failures, right? Right. There's no way you can get out of that with these studies. Yeah That's gonna require full lymphodepletion. As you go down the road, some of the patients that Georg Schett has treated in Germany- Mm-hmm ...who have been less severe, You might be able to prevent those patients from actually progressing. Very interesting. That's a little bit earlier in the treatment paradigm, but where we'd like to be long term. Are there safety risks associated with full lymphodepletion? Like, do you need to weigh that against There are always safety risks. It's chemotherapy. Patients are gonna have chemotherapy like reactions to chemotherapy. Yeah. What we've... You know, we spend a lot of time with patients. I'm a patient advocate myself, so I spend a lot of time with patient advocacy organizations. For the most part, while the thought of going through the chemotherapy is daunting for them, then they get in these trials and they realize, you know, it's a couple of days and then, you know, a lot... Particularly the results they've seen with the CAR-Ts etc., you know, They've been in the clinic a lot longer than we have. The patients are just willing to do it because, you know, being able to just get off something awful like a steroid. Yeah. Right. The possibility of doing that, or maybe being on lower doses of steroids. Yeah Would be very helpful for these patients. Very helpful for them. That's what we think they're going long term. Immediate, sort of worries about lymphodepletion, take it seriously, use the safety, you know, the safeguards for it. Mm-hmm And it's, you know, not really having that bad of an impact on enrollment because these patients need something that's gonna work for them. Right. Yeah. These are lower doses than what's typically administered in the chemo setting. Okay. Cyclophosphamide is one of the tools that rheumatologists also have. Yeah. That's right Trying to kill, you know, bring B cells down as well. Mm-hmm. Again, like Paul said, something, you know, the field will monitor over time. Yeah. I think that benefit of, you know, multiple years of drug-free remission. Mm-hmm Even a couple of years, I mean, that's hugely transformative for someone. Definitely. Yeah. Maybe, We mentioned the other companies. We never worry about mentioning the other companies who are pleased that everyone's doing what they're doing. You wanna talk about the results that other people have seen with NK cells? Yeah. I think the closest data to sort of what we're working on is a CD19 CAR-NK out of China from RUI Therapeutics. Mm-hmm. Really interesting data that was published, in The Lancet in November, and they also presented updated data at ACR in November. Mm-hmm. If I recall, if you look at patients that were dosed, who had at least 12 months of follow-up, they were at, you know, nine out of 13 in DORIS remission at 12 months, I think 10 out of 13 at LDAS. Mm-hmm. You know, on the, on the measure of some of the more. These are all SLE patients, so systemic lupus. In the measure of sort of the types of remission that are meaningful in that patient setting. Mm-hmm You know, they're up in the 70%-76% range. Wow With 12 months remission with an allogeneic off-the-shelf CAR-NK. Right. Their highest dose level that they were dosing was 4.5 billion cells. Okay Given either 3x or 5x over, you know, the course of like a week to two weeks. Which is where you guys are headed for. Yeah. So that's sort of, you know, where we're headed to, in terms of that type of regimen. Mm-hmm. These are all with fludarabine cyclophosphamide lymphodepletion. Okay. It mirrors our approach. Right Very much. Yeah. I think as a data point to give us confidence. Mm About sort of the potential types of They published it, right? Yeah. It's published in The Lancet now. Yeah. I think that's a really great data set that, you know. Yeah We're excited to fully, you know, maybe recapitulate something that like what they saw. Definitely. Yeah. Sorry, what's that company called, the Chinese company again? RUI. R-U-I. R-U-I. R-U-I. Yeah. Yeah. Have you guys thought about bendamustine? We have. What's the protocol on that? As an alternative? Mm-hmm, to these. Yeah. I think if you look at some of the data that, say, Fate has put out, you know. They have the fludarabine free. It's either cyclophosphamide only or bendamustine only. They're not seeing complete B-cell depletion in those patients. As we're thinking about, you know, what we saw from cyclophosphamide, we weren't seeing complete B-cell depletion. Our perspective was, look, the space has generated or generated the excitement when everybody was jumping on this, when Chet's initial data came out. As it continues to build, it's all based on fludarabine cyclophosphamide followed by cells. I think to give the program the best chance initially to see sort of where it can go in sort of this more broader population that we're looking at until, you know, maybe we figure out other specific patient subsets where we can focus later on, I think that's where we wanna be, is sort of maximum effect opportunity. Right. I think the key message about bendamustine and other things is to get it right the first time with fludarabine cyclophosphamide, compare that to other therapies so that you can actually do those. You can't do head-to-head comparisons without head-to-head trials, but at least be able to show what you've got compared to what others have seen, knowing that you're gonna see the full B-cell depletion. In the future, in our clinical development, think about how to minimize any kind of risk associated with lymphodepletion. I think Cabaletta actually did a nice sort of approach to this where they started with fludarabine cyclophosphamide. They're doing their registrational trial in dermatomyositis. They're talking about a registrational trial now in systemic sclerosis. Mm-hmm. They're adding an arm to their LN study, which was fludarabine cyclophosphamide. They're adding a new arm that is lymphodepletion free, right? They sort of built up and they're moving forward in their registrational, but now they're looking to explore, which I think is the right time to show that it works. Yeah ... you can start tweaking. You can do it. Yeah And see if there's other ways to, you know, maybe lessen the burden. Mm-hmm. Okay. maybe finally, you wanna,... Oh, you're supposed to ask me a question now. Yeah. What can we expect from Nkarta in 2026? Yeah, 2026. Now that we've gone through all the staggers and all of the initial kinda getting through, getting to the right place so that we can dose as many patients as we wanna dose. Mm In the middle of the share update on both studies, with meaningful data and meaningful number of patients with meaningful follow-up. That's coming out sometime this year. We haven't said middle of the year. We haven't said middle of the year. We said sometime this year. Sometime this year. Sometime this year, between now and the end of the year. That's for both Ntrust-1 and 2? Both. Yes. Yeah, both studies. Yeah. Yeah. We wanna target one of the main rheumatology medical meetings for the update. Okay, that makes sense. Definitely a goal of ours this year. Yep. What about our cash position? Yep. Our 10-K will get filed soon, but we ended the third quarter of last year with about $316 million in cash. We have runway to 2029, we feel like that's a opportunity for us to really put out this first data set, have plenty of runway on the back end of that as we can look for the data to mature over time. Mm-hmm. We're not in a position where we have to do a financing imminently or on this next data set. You know, our focus right now is we have the capital, so we need to focus on execution and getting to data and really trying to, hopefully with this update as well, be able to articulate sort of the next steps for the development of the program with some updates on regulatory interactions that we would have in 2026 as well. You said 316, right? Three. 316. Yeah. Yeah. Yeah. Okay. I believe you also have an IST-sponsored trial. Two. Is that right? Two. Yep. Okay. One at Columbia? Yep. One in Florida? Where was the... Yeah. The one in Columbia is in systemic lupus. Okay. Um, and then- The other is in MG. Yeah. The other one is myasthenia gravis- Okay That's with UC Irvine and University of Kansas Medical Center. Got it. Okay. Will we see data from those this year as well, or? We haven't given an update on that. I see. Yeah. Okay. Yeah. With those, because they're the ISTs, we're gonna work with the investigators and sort of... Ultimately, it'll be their call, but we'll partner with them to think about what that update looks like. Sure. Yep. Sure. Any questions from the audience? Can I ask what the donor profile looks like, the NK cells? These are healthy donors. You know, we've got some basic criteria that we look for, and then we just get leukopaks from them and isolate the NK cells. Generally, these are healthy individuals. Not like blood type or anything like that? No. Okay. What's the purity of the specimen? How much of your specimen or your dose is NK cell? It is pretty high purity. We've never talked specifically sort of about what that is, but these are effectively all NK cells. When we talk about the dose that we give, those are the CAR- CARs CAR-positive, the CAR-expressing NK cells that are in that dose. Okay, we've done our questions. My turn? If you have any. Great. Yes. Just kinda going back to lupus now. Based on what we've seen with CAR-T in lupus, how durable does a response have to be? I know you cited the RUI data also, but are you looking at kinda 6- 12 months off therapy being enough, or is it much longer than that? What are you hoping for? I think we're feeling like probably 12 months. Mm-hmm. Around 12 months is probably the benchmark. Is the right point. Okay. I think the other interesting feature, you know, that we didn't mention earlier is that this is a therapy that can be redosed. Redosed, yeah. Okay. It's not a one and done. Mm-hmm. It might be, but it doesn't- It could be. ... it... The point is it doesn't need to be. Okay. If a patient goes into a remission and it's on... you know, it's a year, I mean, I think that's an incredible year for that patient. Yeah. If they relapse and they need to come back in, we can redose. Okay. We've done this in oncology where we redose in the context where we had patients that achieved a partial response. Mm-hmm. We gave them another cycle of cells. Mm-hmm. Every patient that had a PR was driven to complete response, and then we had some patients who relapsed after several months or after a year, after getting a complete response, and we were able to put them- Yeah ...i nto CR with another cycle. Yep. So- Remarkable ... as long as there is CD19 expression to some level. Mm-hmm ... in those B cells, which we imagine there would be- Right ... unlike oncology, we don't expect as much sort of antigenic drift. Okay in the autoimmune disease setting. We think that that gives us flexibility where it doesn't have to be a four-year, five-year drug-free remission. I mean, that would be amazing. Mm-hmm We definitely can redose and we can have short time points. Do you kind of see that type of episodic therapy as being more mainstream, or I guess, what do you envision? Look, the ultimate goal is you would love to be able to give patients one dose of these cells- Mm-hmm ... and have them go into complete remission for a long period of time. The reality of these autoimmune diseases. Mm-hmm ... figure out how to work around things. Yeah. To be able to redose is a positive thing. Okay. Whether you'll need to or not is another question. Right ... the capability of being able to do that is there for, with NK cells. Yeah. Yeah. I think a lot of it's gonna depend on the patient, right? If it's a younger patient that maybe hasn't had as much exposure to immunosuppressants or steroids. Right ...and their immune system maybe is a little bit more overall intact and, slightly more robust... Mm-hmm ... than, say, someone who's elderly. Right. Maybe they have a better chance of getting an immune reset where that naive immune system now comes in and has enough juice to really overtake the system and keep the pathologic B cells at bay- Exactly, yeah. ... and prevent them from reemerging. Maybe someone who's older, whose immune system is more depleted and more beat down. Mm-hmm You know, they may not have the benefit of that youthful immune system kind of resetting. Right. Even in those patients we've seen through the literature, you know, they're getting some pretty meaningful drug-free remissions. Wow. Yeah. Another place to look at further down the road in clinical development is as the patients get older, 'cause a lot of patients with these autoimmune diseases- Mm ... some of them, they're in the autumn of their lives. Mm-hmm You wanna be able to treat those patients. The thought is that I'm 66 now. I've had Crohn's disease since I was 13 years old. The thought that my immune system wouldn't be as viable as someone like, is hard for my ego to deal with, right? We wanna make sure that we're able to treat all the patients. That'll be a little bit down the road but yeah, the, some of the younger patients that Georg Schett had originally treated. Mm-hmm Think that was a really nice thing to see that, you know, get them early, prevent them from going through 45 years of steroids. Yeah. No. It's really important. Transformative. Transformative. Yeah. Yeah, definitely. From a safety standpoint, how many times do you think a patient could be retreated, or is there really no. Well, I, we have to figure that out, right? Right. I mean, Right now, as Nadir said, in oncology we had all those examples of PRs converting into CRs. Mm-hmm With retreatment, or CRs that relapsed becoming CRs again. The ability to do that with NK cells, we've established that. Yeah. Definitely. Would you use it as a rescue for people who have done CAR-Ts for autoimmune and it failed? You'd like to get there, yes. Absolutely. Yeah. Yep. In our oncology trials, that was some of the patient population- Yeah ...l ooking at, the more severe patients. I mean, the problem in early stage clinical development is you're always going after the sickest patients. They have the least likelihood of a positive outcome, right? That's where you end up. You wanna end up there. Mm-hmm. Right? You really wanna end up there. Among all of the different trials, well, the two trials that you have going on, all the different indications that you're in, which ones do you think offer the clearest and fastest proof of concept for NKX019? That'll be determined as we continue to enroll the trials. Mm-hmm. It's... I mean, even in the area of lupus, which was really crowded. First, oncology was really crowded before, and then everyone moved to lupus and it got crowded. Mm-hmm. Now lupus seems to be loosening up a little bit in terms of patient enrollment, maybe because patients have seen the effects the CAR-Ts have and... Mm-hmm ... Again, these patients who are living in these rural areas, they don't have access to MIT or... Mm-hmm ... you know, Harvard Medical Centers, they're out in Worcester or they're out in upper state New York. You wanna be able to get those patients treated. Right. I think more of those patients are starting to see that these trials and more of our trials, Fred has done it with Artiva, have gone into the community setting... Mm-hmm ... like we're going into where you can get to those patients. Yeah. When people say that enrollment, you know, or the lack of enrollment may speak to the fact that the market's not there, I think what they're not taking into account is that we're asking these patients to take, you know, days out of their jobs and days out of their lives to come to these clinical trials, and they're giving up a lot to do that. Mm-hmm Getting these clinical trials out into those community centers, really, really important. Yeah for the future enrollment. I do think that our intention later on in this update is to also give a little bit more on- Focus where we're gonna. Mm-hmm. Right. Yeah. ... from these five indications into maybe the one or two- I think we're all excited to see that. ... we're really gonna kind of hone in and focus our energies going forward. Okay. We're lucky to have the cash, so we can do a few of them. Okay ... if we want to, yeah. You'll share all of the sub. We will ... different- Yeah. The plan is. indications ... share across all the indications. Excellent. Yeah. Kind of what are the benchmarks you're gonna be using to narrow down which indications you're gonna focus in on? Where we see the best results. Playing it simple. Yeah. That's what I thought. Okay. Great. Well, if there are any other questions from our audience. How's your biomarker and what testing are you using to track the efficacy? It depends on the, on the indication. You know, from lupus nephritis, it's a lot of kidney measurements to look at protein levels, creatinine, etc., in the kidneys. Systemic sclerosis, depending if it's more skin predominant, then we're looking at skin scores. A lot of these, some of these are early indicators where you can start getting a signal if you're seeing an improvement. Others take longer. To, you know, the earlier question kind of around, you know, how much time do you need to wait to see? For some disease like systemic sclerosis, you know, sometimes the earliest you might see something is six months, but it's really 12 months when you get a better picture of the response. We have an appendix of these things in our board book. Mm-hmm. This Thursday we have our board meeting, and it's amazing how many there are in each one of these diseases. Some of these disease activity indices are so broad, right? Some of these biomarkers haven't been validated yet, but that's our intent is to validate these as we move forward. There's other things like the double-stranded. Yeah the DNA antibodies. Other biomarkers ... other biomarkers- Yep ... that are hallmarks of these pathogenic B cells that you wanna see ideally going down. Yeah. Are they blood tests or saliva or? A lot of it is blood tests. A lot of it is blood tests, skin scores are measured by actually measuring the skin thickness using calipers and other things. Yeah. For interstitial lung disease, it's a breath, an oxygen capacity test. Great. Thank you. Okay. Hopefully we just pioneered a new fireside chat. I love it. Yeah. All right. Good. Cheers. Thank you. It's great. Thanks.