All right, we're going to go ahead and get started. I am Stephen Willey, one of the senior biotech analysts here at Stifel. I'm glad to have with us in the next session Nkarta. I believe they are fresh from ACR, at least David Shook, the CMO, is with. I am too. I'm tired from ACR, not fresh, but I got in at 1:00 A.M. I'm staying with the CEOs here as well, as you can hear. But I'm caffeinated. You guys want to make any kind of opening statements before we get into? Do you need us to? In the Q&A? I don't need you to do anything, Paul. All right. Then why don't you just jump in? All right. We can just jump right into questions. So maybe in terms of clinical trials, you guys have activated a number of these in recent months. I think patients are now being screened and dosed in a couple of these already. Can you just provide a general outline of the clinical development strategy that you're pursuing between the company-sponsored trials, NTrust-1, NTrust-2, the IST at Columbia? And then what specific questions are you trying to address here, and how is this data going to inform next development steps? We just talked about this five minutes ago, so I have a fresh answer for you. All right. OK, so we have an incredibly collaborative relationship with our ISTs, and we have a well-integrated clinical trial strategy in autoimmune disease for which Dave will tell you what we're doing. In terms of data readouts and things like that, we've guided to 2025, and we expect that that would be the time frame in which anyone that's doing any clinical trial with an Nkarta cell is probably going to have enough data to be able to present. What we will not do, as you know, because I announced it at your meeting in July, is report out patient-by-patient data, patient case reports, patient testimonials, or anything like that. Is that helpful? That is helpful. OK. Yeah. So right now, as you mentioned, a few different clinical studies happening. So the first one we opened was the NTrust-1 clinical study that's in lupus nephritis. That was opened in part because of the enthusiasm around lupus nephritis, initial proof of concept out of Erlangen and others. So that one is open, enrolling, and dosed. The NTrust-2 we opened shortly thereafter to expand our footprint in B-cell-mediated autoimmune diseases. That's in inflammatory myopathies or myositis, systemic sclerosis or scleroderma, and then ANCA-associated vasculitis. And we went after those for a couple of different reasons. One, lupus nephritis is very busy, but also those are very clearly B-cell-mediated, where the pathophysiology is driven by pathogenic autoantibodies. And we felt like the proof of concept, either directly through available therapies or standard of care or indirectly through disease mechanism, that we felt like those are good opportunities there. is a lot of enthusiasm there, certainly among our investigators and around us, ACR and others. Our first IST in systemic lupus came from this investigator, Anca Askanase, out of Columbia, who I entered into a conversation with her and said, listen, everybody's going to lupus nephritis. I've got a million protocols pitched to me in lupus nephritis, and you're leaving all these other patients out. There's tons of patients with lupus. What about rash? What about arthritis? What about pain? What about fatigue? What about all these other things? They're not on these studies. And I said, can I open this one? And so we had a good discussion and opened this as a way to help understand how big of an opportunity this was, because at the time, really all the POC was in lupus nephritis. So you talked about how lupus is a very busy space right now. Obviously, the FDA is requiring all of these novel modalities to step through these kind of very severe refractory patients. How are you thinking about competition in the space, not necessarily from a data perspective, but just your ability to enroll these studies in a timely manner? And then kind of what have you done or what are you doing to try to improve your visibility and your positioning there? Visibility-wise, let me take a step back from this whole thing. Right now, I know you said you didn't want to talk about data, but let's just give you a little bit of a data point. Probably the largest body of data that's out there now is collective autologous CAR-T. Everything else right now is a couple of patients here and there, including we're not talking about our patients till we have enough to talk about. Enrollment and data is going to drive enthusiasm in the space. To get enrollment and data, we're competing with 60 other companies, with bispecifics, T-cell engagers, cell therapies. The good news in the cell therapy space is we're one of very few companies, if not the company in the lead, in the engineered, off-the-shelf, on-demand, allogeneic NK space. So our other competition in cell therapy are CAR-Ts, mostly autologous CAR-Ts, some allogeneic CAR-Ts. But in the space in NK cells, we're in a pretty nice position because there aren't many people doing NK cells. So in that space, we're very much in the lead. And we compete in that pack, but we're also competing in terms of patients and investigators for sites, for investigators, et cetera. And the good news there is what Dave's done and his team has built a network in the physician-investigator community that's broad and wide. We have a rheumatologist, sorry, not a person with rheumatoid arthritis, but a rheumatologist. She's amazing. She's working with the PIs. We just came back from ACR where we sit in the lobby of the hotel at the Convention Center, and people just gravitated towards her. So she's got a great background, has great relationships. We also have very grassroots, intense relationships with all of the patient organizations. So these guys spent their time going to clinical and poster sessions. I did that too, but I spent my other time meeting with the patient groups, myositis, myasthenia gravis, vasculitis, lupus, each one of them, scleroderma. Each one of them has three or four patient groups. And what I'll tell you about patient groups is that they have awareness, astute awareness of cell therapy. They have astute awareness of other new modalities, and they're interested in cell therapy trials. So that's good. So we've got a lot of things that are in our favor because it's going to take patients, physicians, and data to determine who's going to win in this space. And we're happy to be competing in this space with a lot of really cool players that are working really hard alongside of us. That's right. I think last time we connected in person in Newport, you were on your way to host a golf tournament sponsored by the Lupus Foundation, if I remember correctly. LADA, the Lupus and Allied Disease. Yeah. All right. I'll add from a medical standpoint, I think the differentiation here in autoimmune disease, much more so than malignancy, safety is at a premium. One of the things that has sort of taken the shine off the initial Schett data and others is the accumulation of initially thought to be one-offs, now more consistent CAR-T expansion-related toxicities, CRS, and ICANS, where it has really kind of cast a pall over the space and maybe throttled back some of the initial enthusiasm. Things that those kind of toxicities, like prolonged cytopenia, infection, ICANS, et cetera, which have always been a part and intrinsic to CAR-T, are showing back up again, where initially it was thought, no, that's not going to be seen in this patient population. One thing that NK cells have always done well is be safe, be accessible, be scalable. So this is a big opportunity in a big patient population that demands a safe, accessible therapy. In oncology, the idea of bringing cell therapy, next-generation therapies to the community is nice, and we've been at that for a long time. Here, this is necessary. This is where these big groups of patients live and are treated. The enthusiasm for cell therapy and immune-facing therapies in autoimmune disease was not for the few thousand people with refractory lupus nephritis. It was for how big can this go? How impactful can these diseases, these therapies, be? And so as you start talking about cell therapies, how can you expand the manufacturing, the accessibility? How can you deliver these as an outpatient, put these in the hands of a rheumatologist, et cetera? That's where we feel like that's a differentiator for us, is to be able to have an advantage in safety and accessibility. Yep. So by the way, if you want to know how brilliant some of these patients are, I had dinner last night with a group that I just met for the first time last night called LupusChat. They're young women with lupus that are living all over the country. And they're in dispersed geographical locations, which is where all the lupus patients are, right? And none of them are living well, some of them live in Manhattan, right? But for the most part, they're living out Long Island, or they're living in Worcester, Massachusetts, or they're living in Ashgabat, or wherever. And so through the podcast, they educate each other on where the sites are, what the therapies are, what all the modalities and the differences in the modalities. And they're pretty impressive. Do you get sense from some of these patient groups that they're not deemed to be eligible for these trials because they don't have "baseline disease" that is refractory to the point that the FDA is allowing them? That's right. That's okay. Yeah, yeah, we do, and I think for the most part, well, it's rare to meet people in the patient groups that haven't been through multiple rounds of therapy. I met a 17-year-old girl. She was on a panel at ACR last week, and 17-year-old, been through five therapies that didn't work and is on multiple drugs, so they get on a lot of drugs very quickly because most of them don't work, and most of them are awful, and the primary candidate there is steroids. They're all on steroids. The conversations they have are more about how many milligrams of prednisone they're willing to take or not take, and so they're really interested in new modalities: antibodies, T-cell engagers, cell therapies, but they're probably most knowledgeable about auto CAR-T. Our job is to educate them about allogeneic NKs. OK. And I do want to talk about steroids and just tapering background therapy, et cetera, at some point. But you talked about the safety profile of 019. You're obviously coupling that with kind of a logistically advantageous lymphodepletion process where you're dropping fludarabine. So we've had some conversations with rheumatologists who seem to maybe have a little bit of a dismissive perspective around kind of what the dropping of fludarabine means. And they just kind of view cyclophosphamide as just it's lymphodepletion, right? I need to do it with a CAR-NK, I need to do it with a CAR-T. Do you get similar feedback? And is there anything that you think kind of explains this disconnect at all? I'd say there are varied opinions, and it has to do with education and awareness of these medicines and kind of what they've learned, either in who they've learned it from. Certainly, if you're looking to say it's not a big deal, that's going to be your education, but I would say there is some variance in opinion. In general, I think less chemotherapy is better. I think generally everybody acknowledges that. I think the disconnect becomes, OK, how bad is fludarabine, and what do I get in exchange for it, and if you say, hey, it has this risk of prolonged cytopenias that we see, it has this neurotoxicity risk, a secondary malignancy risk, and they say, yeah, but how high? And what do I get in exchange? And if it's for a lifetime of drug-free remission, that sounds OK, pile it onto the cyclophosphamide. But those kind of conversations become more relevant as you talk about, well, what do you get in exchange for that? If you say, hey, you do accept a risk of prolonged cytopenia or secondary malignancy or whatever it is with fludarabine, and it'll buy you two years of drug-free remission. Then it becomes, I think some of that early stuff was about the concept that this is a one-and-done. And it was like, if I'm going to bomb them, just bomb them. Pile on the drugs. Get it all done once. And so I think as we understand what the toxicity profile is, people get a little bit more awareness of that and how dependent the space will be on fludarabine. I think there'll be some leveling out. So yeah, there's varied opinions on how that goes. We certainly feel like it's important enough short-term and long-term benefits that we would evaluate it on a silo. Can I add one more thing to that? Yeah, of course. Women of childbearing potential are not thrilled about cyclophosphamide or fludarabine, right, so part of this is how appealing a clinical trial and ultimately a commercial product is to the population that takes it, and so if you talk to a rheumatologist and say, would you give fludarabine? The answer would be, if I think I have to, I will, right? If I think I'm going to get your Schett data out of this, then I will do that. I would prefer not to, so I will also tell you, I had one conversation with a rheumatologist last year at ACR where that person said to me, why do I need cell therapy? I have steroids, so I think sometimes it depends on who you talk to. There are a number of really very good academic rheumatologists out there. And there are a number of folks that have been doing rheumatology for years. And the population, it's a big population. And so I think what we all need to do is make sure that the key opinion leaders that are actually doing the clinical trials are paying attention to their patient population and what's going to be in their best interest short and long term. And we probably like the idea of having optionality for those clinicians and those patients so that they can make their own decisions there. I guess the question was kind of asked in the context, maybe, or poorly asked in the context of also knowing that you were getting requests from the oncology community to see if you could drop fludarabine, right? So is this just a function of there's a user experience in the oncology setting that doesn't yet exist in the rheumatology setting? I mean, I think. I'm not sure that's the case. I think it's can we differentiate in a way that's meaningful to and lines up with our product, right? We know NK cells and T cells are fundamentally different. The biology is different. The way they expand is different. The way we use them is different. The need for LD is different. And so here, one of the main drivers here and what we felt lined up with our platform nicely is cyclophosphamide is used as standard of care. It's been a control arm for some approvals. And if we, in a Cy-only approach or a fludarabine-free model, the pathway for registration becomes much cleaner and where you don't have to worry about contribution of component of fludarabine, rituximab, IL-2, whatever that you're adding on top of it. And then we know that cyclophosphamide alone therapy provides maybe 30%, 40% renal response alone. The addition of one agent to that, and you see others going that way of adding on to standard of care. The addition of one agent onto standard of care. Belimumab was approved with a 4% or 5% incremental add against baseline MMF or CYC. As CYC alone, you don't need Erlangen data to drive an approval. And And to say, hey, rheumatologists, before you get to before we totally revolutionize the way you treat, add this one agent on to the agent you're already using, and you'll get a 20%, 30%, 40% bump in your responses without. We've treated 40-plus patients with 019, never seen ICANS once, never seen life-threatening CRS before. Those are real data we're able to share and to be able to feel like we can maybe incrementally add to the practice in a way that lines up with our, I mean, that's what the hope is, and if you work your way, I don't want to say backwards, but if you work your way from refractory patients to more diverse patient populations, you start looking at arthritis and MS or pediatrics, right? Then that becomes a much more discriminating set of physicians and patients about whether they're willing to give something like this, so if you could, I mean, I wish we had all the money in the world to do this so we could just get there as quickly as possible. The younger patients with intact immune systems are likely going to respond well to cell therapy and prevent the future awfulness that comes with these diseases. So it also depends on the disease. We talk a lot about lupus nephritis. But when you look at some of the other indications we're looking at, there may be less of a tolerance for fludarabine. And particularly, I attended a pediatric session at ACR. And one of our principal investigators was saying that even ACR is going in the direction of treating younger and younger patients in these studies and trying to help the peds. That's going to be fludarabine would be a pretty tall order for the kids, right, Dave? Mm-hmm. So maybe we can talk about the differential dosing strategy that you guys are pursuing in NTrust-1 and NTrust-2. So NTrust-1 is kind of the conventional day 0-7-14 schedule. NTrust-2 is the compressed day 0-3-7 schedule. Why look at different dosing schedules in different disease states? And I guess, does this complicate your ability to interpret the data across the two trials? So i.e., if you see a differential response in NTrust-2 versus NTrust-1, how do you know if that's a byproduct of the dosing schedule versus just the subtype of the autoimmune disease? Let me just say before Dave dives into that that the goal is that they will all be on the same compressed dosing schedule. One of them just happened to get approved or cleared before the other. And then we started the second one with the right regimen. And now the goal is to get them all on the compressed dosing regimen because that's giving more drug more upfront in a compressed period of time, which is better for the patients. It's much better for the convenience of taking the time out of work to get your therapy, whether in a clinical trial or even commercially. OK. Yeah, exactly. I mean, I think we know there's the impact of dose intensity of moving more proximal to LD. We get better PK. We get better dose intensity without having to ramp the dose up as high. And when we filed the NTrust-1 IND, the compressed dosing PK and safety data from the NHL study weren't even started. We filed the compressed dosing without those data. And so when NTrust-2 came around, we had safety data that we were able to use as a part of our filing package. But as Paul said, the plan will be to consolidate the platform. OK. And so you just actually touched on some of that compressed dosing data in non-Hodgkin's. I think it was a week or two ago. And it looked like, I guess, just per the responses that you were seeing, mostly partial responses, I think maybe a CR with a retreatment. If you look at the conventional dosing schedule used in NTrust-1, you saw a couple of single-cycle CRs in some patients. And so if I'm an investor and I'm looking at these two non-Hodgkin's data sets. The second one is. How do you look at the compressed dosing NHL data and maybe not view that as an indictment of the compressed dosing schedule? So how would you message that to an investor who would look at the compressed dosing data and say that this doesn't look as good in non-Hodgkin's? Yeah. So first and foremost, they're drastically different data sets. So the initial NHL data set was a mixture of indolent and aggressive lymphoma with some, and we actually saw very good responses in aggressive diffuse large B-cell lymphoma, or autologous CAR-T are well approved. In this setting, we knew and we heard from investors, from investigators, from analysts, others said, if you're not active post-CAR-T, you're not a drug. And so we specifically said what's the most aggressive. We took everybody in that cohort as aggressive diffuse large B-cell lymphoma that had failed CAR-T and often bispecifics as well. So that was the end of the line. And so we're actually very encouraged by the amount of activity that we saw in that patient population because of, obviously, historically, lots of allocell therapies and even autocell therapies kind of hit that wall of post-CAR-T. And that's where the responses stopped. And so in this population, we were able to make inroads in a very difficult patient population that had failed CAR-T, show a response in most of them, and drive a pretty long CR without retreatment or multiple cycles. And in that population, now we still believe that there is activity there. It would likely be a more involved study to show that. And so we've opted to deprioritize that product or that disease state right now. But we were still got additional safety data to show you can give those doses in seven days versus 14 days, get good PK exposure without compromising safety. Paul, you mentioned steroids as use of background therapy in lupus. How is the NTrust-1 protocol? How does that allow for the tapering of background therapy? And it seems like a lot of the KOLs out there are kind of using this drug-free remission as the gold standard that maybe all these sponsors should be held hostage to. Do you agree with that? And does the protocol of NTrust-1 allow you to achieve that? That first part's for you because that's your expertise. Yeah. So I think that was what the pitch was, right? Cell therapy of Schett and others was not an incremental add-on standard of care. It was the drug-free remissions. And so that's what everybody is shooting for, and ourselves included, is to be able to look and say, yes, no reason to think we can't replicate those data. It's certainly pulling off background immune suppression. In terms of steroids, it's a challenging one because some patients are on steroids for a really long time. And even in a remission state, stay on a low dose every other day, sort of physiologic dosing. The study does have guidance on weaning off, certainly coming off of background therapy, and guidance on coming off of steroids or maintaining low levels of steroids. And what we've heard is maintenance of low dose or physiologic steroids is not as a deal breaker as staying on therapeutic doses of steroids. So yes, we'll be looking to pull off background immune suppression. We do think that's the promise of cell therapy. And then steroids to pull off of certain treatment dose. And if patients or physicians feel like they need to stay on low dose background, so physiologic dosing, because they've been on it for 20 years or something, there's a little bit of flex there. Now, the good news there is that the patients are aware. The number one question I get from the patient groups are, "So how long do I have to get off my background therapies for?" They'd love to get off steroids, by the way. Hate steroids, right? So I think the big issue is if they finally found something that works somewhat. So back in the days of drugs like beta interferon, when it worked somewhat, at least somewhat's better than nothing, right? If they're somewhat controlled, they don't want to not be somewhat controlled. And so their awareness of how long from when they taper to when we dose is important. And that's a big issue that we have to deal with across the board, whether in trials or commercially, is you can't let that go too long because they're going to relapse. And then you're going to have a patient that's going to enter trial or a therapy where they're going to be in a raging relapse. It's not a good place for them to be. OK. Maybe a few more questions here. So maybe for you, David. So I guess when I go through some of the lupus literature, there seems to be this suggestion across most of which I've come across of the role regarding longer-lived plasma cells in terms of their role in the underlying pathology of the disease. We know that CD19 is not touching this subtype, right? All these patients have their humoral immunity intact. How does that make you think about kind of what the longer-term durability data of anything CD19 targeting might be in the setting of lupus, whether it's a CAR-T auto, whether it's a CAR-NK, whether it's a bispecific? Yeah. Yeah, I mean, I think the role of LLPCs is really kind of evolving and unknown at this point. And as you said, the humoral response, which is quite protective, is spared in here as it is in oncology. Even patients that have CAR-T, that have CAR-Ts persistent for a year and a half, they maintain their vaccine-associated responses, right? And that's an important safety advantage. And if you make a decision that you're going to target CD38 or BCMA or something and start wiping out those, then you really add on a measure of additional safety concern to these that you want to avoid if you have to. Now, your question of that role of those cells, so far it doesn't appear that relapse is really the problem. There are some patients that are not responding to CD19. So far, the pretty impressive response rate of CD19-directed therapies, in my mind, is the sort of strongest argument that these cells aren't playing a huge pathogenic role. And the subset that maybe aren't responding to 19, maybe there's a subset that will need a 38 or a BCMA-directed approach rather than you get your 19 effect and then the LLPCs drive this remission. Because now we're seeing some of these remissions are a couple of years out. And those LLPCs maintain responses pretty reactively. That's where you get when you get your flu shot or COVID shot or whatever, they'll hold on to it. So it does not appear that LLPCs are playing a huge role yet. But I think that data set is unclear. OK. Maybe last question because I know we're going to get kicked off here pretty soon. But you just came from ACR. I think there's presentation of the first CAR-NK data today in lupus from a Chinese group. Just any thoughts on the data that you saw? I'm not sure. So I haven't seen the updated presentation relative to the abstract, but not sure if you have any. Yeah, we looked at it this morning. So 22 patients, 50% went into CR, a DORIS deep remission, about 2/3 of which went into LDAS, which is another form of remission. I mean, I think what I take is the upside, huge doses, several billion cells, do not look armored with cytokines. So take it for what it's worth. I mean, one, you can get B-cell depletion with CAR-NK cells. You can get immune reset with CAR-NK cells. We'll dive through the data more. But I think that and a couple of grade 1 CRS, no ICANS. It was a late-breaking session on CAR-NK cells. That's a big deal for NK cells. Safety will continue to show up. One of their big slide highlights was very, very safe. All right. Cool. Always appreciate the time, guys. Yeah. Thanks. Thanks a lot.