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All right. Good afternoon, everyone. I'm Stephen Willey, one of the senior biotech analysts here at Stiefel. And apologies for the late start. We're trying to get Nadir patched in, but he is available through Paul's phone, I believe. There we go. So very glad to have with us in the next session and Carta, Paul Hastings, who you see there as the CEO, Nadir Mahmood is the president. He's on the phone. You guys want to make any opening remarks before we jump into Q&A? Nadir, do you want to give a little brief overview? So I'll let everyone hear my voice here. So apologies that we couldn't be on video, the little technical difficulties. But as an overview, Encarn is an autoimmune disease company. We're developing a CD19 target CAR natural killer cell for autoimmune diseases. The cell is allergenic, off-the-shelf. We're administering outpatient, and this is in indications across two company-sponsored INDs. First one, Entrust. There we go. First one is Entrust 1. We just lost him. By the way, this is part of his CEO training, like how to deal with audio-visual problems when they happen. But so the first is Entrast 1, which is in lupus nephritis. And the second is Entrost 2, which the basket study, which has scleroderma myositis, vasculitis, and now rheumatoid arthritis. And as you know, we have upcoming data at ACR. Hold on a second. okay you're back yes okay all right i just went through interest one and interest two so you can take it from there how's that okay now here it is to look at um this potential cell therapy what we've really seen from the the autologist card key space but really deliver this potential therapeutic benefit to patients in a therapy that is readily available off the shelf, on demand, with incredible safety profile that can make it more amenable and more accessible to a broader range of patients. And we're looking forward to presenting our first set of data at the American College of Rheumatology Convergence 2026 meeting in November of this year. And also to have the ability to redose if it's needed. One of the things we keep hearing from investors now is how safe are your cells because of all the safety issues that we've been hearing about and then can you retreat and can you retreat with lymphodepletion and what you'll see is yes we can and so we've done that in oncology we're now doing it in autoimmunity and we're actually seeing similar results that we saw in oncology so we'll be presenting those data either at the plenary session not the plinery but the oral presentations at ACR or at the company event which we will hold at ACRA as well where we'll explain all the data that we have so What we think we have is a safe cell, an effective cell, and one that can be retreated if needed, which is important for patients, right, because it's difficult to retreat with autologous CAR-Ts, et cetera, and case cells are handmade for autoimmune disease because you can do all those things with them. Okay. I definitely want to get to the clinical data we're going to see at the ACR meeting, but maybe you can just kind of first speak to some of the operational logistics underlying Entrust 1 and 2. I know you made a number of protocol amendments earlier this year in agreement with FDA. How have those changes impacted patient enrollment kinetics up to this point? Oh, in an amazing sort of way. So when we went from oncology to autoimmune disease, the FDA basically said to us, I don't blame them, right? You have safety data on oncology, but now you're in a new patient population, autoimmune patients. And as a person with Crohn's disease, I've had it since I was 13 years old, autoimmune patients are going to react differently to, you know, chronic therapies than to an oncology patient with a therapeutic. And so they asked us to start all over on the safety database. And so we actually had to go through these patient by patient staggers. We had to have 24 observation period once they got dosed with the cells. originally where they had to stay within a 30 mile radius of the institution 60 mile radius of the institute for 30 days after they got dosed all of that is now gone because of our safety profile in autoimmune patients so the fda and we work together with a protocol amendment and we now have the ability to dose patients they can walk in get their cells off the shelf be observed for two hours and go home. So all outpatient administration of these cells, no hospitalization time, and the ability to actually be convenient for the patient so that they don't have to sit in the hospital for a week. And then they also agreed with us to condense the dosing from where it was to zero, three, and seven days. And we're looking at a new dosing schedule, which is even more compressed, which we're working with them on now, so that everything we do is for the patient to make this as convenient as possible for thepatient. When you make the investigational agent convenient for thepatient and you provide services for the patients like travel and daycare and doggy daycare and reimbursement for their time if they're missing work and it's on their request alone, then that makes it easy for thepatiant as well. And so when you put all these things together, enrollment started going very well compared to difficult to enroll patients to grabbing them from Albany and bringing them to Manhattan or grabbing them from wherever in Kentucky to the University of Kentucky. So now it makes it a lot easier. Enrollment is up and it's convenient for the patient. And also added community-based centers. So when you take away all those restrictions, even though we have one amazing community center, by the way, it does have overnight stays in their institution. But when you actually open up these community centers, and by the way, I recently heard that Lilly is focused on community-based centers for all of their trials now as well. And I think this is amazing because you can, you know, part of the, you know, with restrictions on trials, it makes them only accessible to patients, which is 5% of the patient population that wants to be in clinical trials is accessible to them when they're in academic medical centers. So when you open it up to community- based centers, the dynamic gets better. And as you can see at ACR, we will be setting you up from logistics to actually tactics. At ACR we'll be reporting in two indications with, you know, a handful of patients in each with durable responses. And so we could focus on the indications, see which ones enrolled well, see which ones responded well. And so now we've gone from a big basket study and we will talk about where we go next, which will be down the path of a couple indications for our pivotal studies. So it's all allowed us, all of this has allowed us to be more convenient for the patient, more convenient for the clinician in the institution to administer the cells and the lymphodepletion, and ultimately enrollment improved in a dramatic sort of way. Okay. I might have to revisit my R&D estimates. I don't think they contemplate. Okay, so we don't want to over-promise and under-deliver. No, I know. So you've dose escalated now up to 4 billion cells per dose. And this is administered on day 037. And I know you have the ability to dose higher if needed. I know, you just talked about maybe looking at a more compressed schedule. I'm not sure if there's anything that you can say there. But can you just speak to the data that you're using to guide dose escalation across all of these different disease states right now? And are these decisions being predicated just upon B-cell depletion, reconstitution, PKPD, or are you actually looking at clinical data to inform dose escalation as well? So, Didier, do you want to talk about what have we said about dose dosing publicly? I want to make sure I'm not having a senior moment here. we're on doom 037 and we're always looking to see if there's other ways to enhance um efficacy while maintaining a clean safety profile so i think dose escalation looking at other ways of potentially compressing doses so i Think the pkpd point steven i think that's an important piece that's definitely one consideration the other thing we're going to look at because now you know if you recall we started dosing at four billion cells um with the flu cy regiment earlier this year so you know we're starting to see data around what that could look like so we're going to use data also on some follow-up of certain revisions to help inform do we need to go higher do we to do something more in terms of changing the regimen to give us an even better opportunity to deepen responses if we need too so those those options are there and we believe we can scale that i don't think they're going to have limitations from sort of a manufacturing perspective if we need to go higher. So what Nadir is alluding to is always looking for the best optimized dose as possible. But what we hope to achieve here, and what we are seeing early signs of, is a dose response curve. The thing about our cells is we like to say that our cells are just like a biologic, right? NK cells don't expand in humans as much as T cells do. The dose you give is the dose you get. So our big 4 billion dose times three, once the patient gets all those cells is about equivalent to once T cells expand, right? So that's a pretty interesting, we hope to be a therapeutic dose. If that 4 billion does is safe, we have the option to go higher. So when you develop drugs, you want to know whether your tox profile is so good and you want to be able to maximize as much as possible your efficacy. So we probably will go higher at some point and look to see if that higher dose is better. But when coming back to your comments about PKPD B-cell depletion, nobody really knows today. We think that full B-cel depletions leads to durable responses. We need to do more of that. And what does full B-cell depletion mean? Some CEOs will tell you it's measuring it in blood. I say that's wrong. Measure the lymph nodes. We're doing lymph node biopsies. We're taking the risk, working with our patients and our clinicians, to do lymph node biopsied. Now, NK cells have a different profile, PKPD, than T cells. They traffic to different areas. But we're still doing those lymph node Biopsies, and we are looking at B-cel depletation. And we're trying to figure out, does B- cell depletition correlate with durable clinical responses or not, because no one's really proven that yet. There's some correlations that are being made, but we're going to do that. We're goingto look at that. But what's more important than the PKPD and, you know, biomarkers, if you will, in this case, B-cell depletion, is how is the patient responding? The disease activity indices associated with all of these diseases, if you think lupus is tough, look at myositis and scleroderma, you you know, look at CRIS and TIS and R-CRIS and M-Cris and all these other disease activity indices. And if you ask a Crohn's disease patient like me about the Crohn disease activity index, I'll roll my eyes and say, are you kidding me? Like, ask me if I have diarrhea, ask me if it's bloody, askme if I can live and not be exhausted. And so we're doing the same study in our myositis and scleroderma and RA patients. Alongside each one of those studies, we're joining a patient reported outcome study separate from our clinical study where We call them in their homes on a Zoom call, and we ask them, in their words, what their symptoms were when they ended the study and what their symptoms are now that they've either responded or not responded to the drug, so that we can come up with, with the FDA, outcomes that make sense to patients, that are more patient-friendly and actually easier to understand from an investment point of view than TIS, R-CRIS, which is a composite of all kinds of different things. And so how's your skin? Is your skin flexible? Can you raise your arms? Can you eat? Can you swallow? How are your taste buds? Can you taste food in the case of scleroderma? So we're doing all those things in parallel. So PK, PD, and B-cell depletion, critically important, equally important, are patient reported outcomes in these highly subjective autoimmune diseases with these patients and the durability of those patient reported outcomes alongside with those scales that they use, which is essentially asking a patient to take a pencil and put it on a line about how they're feeling today, right? These things are not ideal, but we're working on that with the FDA and with our patients and with our clinicians. Okay. I know you also have a couple of ISTs that are enrolling looking at myasthenia and also lupus with or without lupUS nephritis or- SLE, yes. SLE with or without lUPUS nephritis. Is the dose escalation that you're able to move to in the Entrust 1 and to. Are those incorporated into the ISTs? And some of the protocol amendments have been incorporated into those studies as well? In some cases, but let me tell you what we're going to do by the end of this year. We're goingto tell you where we'regoing next, and we're going to go from a huge list ofindications down to a very specific list of indications. We may revisit the ISTsthe other indications that we haven't enrolled as many patients to as much meaningful data as possible but we're going to take the data we have and focus in a couple of different areas so that we can take the capital we have which we have plenty of and get these things through as close to pivotal trials if not all the way through with room on the other side so we're gonna focus first in the key indications we've got great data on with durable responses in large numbers of patients focus on that and then revisit over time these other indications, but we will start with a very focused group of indications so that we can actually focus the company, focus the supply, focus, the clinicians in the, in, in a couple of different areas. And we expect that those areas will be relatively easy to enroll refractory patients who really want a therapeutic and where it's not so crowded that you can't enroll more than one patient every other year in an academic medical center. So that's where we'll go next. Okay. Maybe getting to the ACR presentations specifically, I know that you're a bit limited with respect to what you can say here, but maybe you can just provide a high-level framework of what we should be expecting to see in terms of patient numbers, duration of follow-up, and then just some of the specific efficacy metrics that you hope to share in an effort to provide proof of concept. Yeah. Nadir, do you want to take a crack at that? And I'll add to it if I need to. So we have three presentations at ACR. The first one is an oral presentation on myositis. And we have a poster presentation on scleroderma. And then there is a third presentation, which is also oral, on the last day covering safety, which is unusual to have a safety-only presentation at a major conference like this. But it's really an opportunity, I think, to demonstrate, especially given what we've seen with the autologous space recently the potential for a truly safe outpatient therapy in the setting so in terms of data as you can see we are focusing our presentations on two different indications from the six that we have across the two is the two ind studies and so the whole idea here is this is where we're driving our focus and our emphasis right now. And so what you can expect there is, as Paul mentioned earlier, about a handful or more patients that have about three months more or more of follow-up. And so the idea there is to start having not, you know, one or two patients, but we've always wanted to have a meaningful number of patients at a clinically meaningful dose with some relevant amount of follow up that we can share to talk about why we are excited and what we're thinking about those particular indications and so when you think about this process that we've gone through right not your typical cell therapy dose escalation but more like a traditional pharmaceutical or biologic style dose escalization going from 1 billion cells to 2 billion cells now to 4 billion cells and so now that we are at what we believe sort of is is a is a dose that can deliver data that we can talk about in terms of what we think the program can go, that's really what we want to present and what we wanna have in the myositis presentation in the scleroderma poster. And then the safety is gonna cover sort of the entirety of the program across all indications, all dose levels to sort of show what we've been able to see from a safety perspective. So we'll have a community-based academic, Dr. Valenzuela, presenting the myicitis data in an oral presentation. We'll have Dr. Dinesh Khanna, who is world-renowned in scleroderma, present the scleroterma poster the next day. Then imagine getting an oral presentation on a safety database, right? This is why this is so important to ACR and important to rheumatologists to understand how safe these cells are. We got an oral representation, which Dr. Valenzuela will give. And it's important to note that Dr. Valenzuelo is the highest enroller in our studies, community-based center, right, academic, academically trained owns his own community-based center so he will be given that oral presentation on that last actually late breaker day is when they gave us a oral presentation even though it's not a late breaker because we submitted the protocol uh the uh abstract the time so one oral on myositis poster on scleroderma and an oral on safety across all of our indications right not oncology and then a company-sponsored event which we'll do well we'll pull it all together. And then I want you to pay attention to the dose response, because we'll have patients, you asked about durability, Stephen, there are patients that were on 1 billion, 2 billion cells. If they're respondents, they're going to have more durability, right? So you can connect the durability of responders at lower doses to where we are at higher doses. And then you can look at, you know, not a lot of retreated patients in autoimmune disease, but maybe one or two that have been retreated. Did we deepen the response the way we did in oncology? In oncology, we had patients that came out of CR that we retreated, put them back in CR. Are there patients in autoimmune disease that maybe weren't a TIS 50 or greater that we then retreated with a higher dose and got a Tis 50 or later after the first cycle of dose? We're going to see that. And so what we hope you'll see is a dose response, like a traditional therapeutic, which I think people will be excited about. It's a cool story. And then you'll See the ability to retreat, not the necessity, but the ability to retreat and why that's important if patients don't respond the first time. What if they respond somewhat the first time and maybe have some unforeseen circumstances in their life and they, you know, their disease regresses a little bit and then we retreat them, what happens then? We'll show that data as well. Whoops, you're on mute, Sian. Apologies for that. I know you kind of acronymed out some of the endpoints relative or relevant within the context of myositis, which is TIS and it's Gliriderma, which is Chris. And I think we've seen some CAR-T data. And Chris and our Chris, yeah. Yeah, correct. And so how do you think about the CAR-D data that we've seen there as kind of an efficacy benchmark that investors might be holding you hostage to? I love it. We want to match their efficacy and give a better safety profile. Simple as that. Okay. And then... And the durability. I want to like match the durability, yeah? Yeah. And then what can you say about background therapy in the context of Entrust 1 and 2? I know, for instance, if I look at like the Kaba data, for example, I think they had patients drop all immunomodulators, you know, prior to dosing. Are you allowing for stable background therapy? And how should investors think about that if you are? You know, we're allowing a certain dose of steroids if they need to use steroids. They come off all their other therapies, though. We don't have, you know, I've heard some CAR T companies, a lot of methotrexate and other agents, particularly in RA. We right now, right in India, we have no immunomodulating therapies or background therapies other than steroids. Is that correct? That's right. Yeah. So when a patient comes on therapy, think of an RA patient. And by the way, we're excited about RA because we think CD19 is a great target for RA as well as the cells, but we're not as far along there because we just started doing that. But if you think about an RA patient, RA patient comes into a trial and you take them off everything they've been on and they might actually have a bit of a flare, right? So you don't want to see that flare. So you want to keep them on a low dose of steroids to kind of prophylax against the flare while they're getting their cells. So that's something that we do allow up to a certain milligram amount. How much additional data, say like in myositis and scleroderma, which you've highlighted, how much additional patient data would you like to generate from Entrust 1 and 2 before you feel comfortable pivoting to registrational development? Well, look, one question we want to ask ourselves is, because you don't want to leave anything on the table, is should we go higher or not, right? And get deeper responses. And that's hard to do when you've got three months of follow-up, but we're going to think about doing that. but we want as much data as we can get. So we're going to keep Entrust 102 going anyway to collect the data, but we'd like to have, what I'm anticipating we will do is over time, maybe one of those retreated patients will become a case study at the next medical meeting. Maybe the next set of data is presented next year at the meeting with more durable responses after you see three months durability, maybe get six, 12 months durability. So I think we'll always be looking at Entrust for the durable durability factor because people want durability. You give people three months durability they want 12 months, you give them 12 months they want 24 months, right? So we want to keep that going and then starting enrolling the pivotal trials as well. Okay. And I know the FDA has been pretty friendly in terms of kind of the patient data requirements, number of patients that have been required for some of these registrational cohorts. I think the cabaletta myositis registritional development effort in that disease is what, 17 patients, right so yeah we we want to go forward our goal and i've told our clinical people sometimes they don't like it single arm trials we've been invited by the fda to do these kind of trials in cell therapy so single arm trial well i'll get someone a placebo if you don't need to right now i'm a little skeptical of this registry concept where you go get a registry of data and try to compare that registry to um to your population in your trial because you have to go to these registries and negotiate all these ridiculous contracts. But if there's a way to look at standard of care and make sure that your results are better than standard of carer through the literature, you want to do that. But in myositis and in scleroderma, you can probably do that given the lack of therapies in those diseases and what's available, IVIG, for example, and other things. So look at that, look at the literature and be able to compare that and make sur that your responses are durable. So they've been great in terms of number of patients. They basically said if you dose escalate And you've got efficacy and safety, we would welcome you to consider a single arm trial. And I think you're seeing a lot of these single arm trials being encouraged. They have a whole initiative at the FDA on speeding the discovery to development effort, and they're being very friendly to cell therapy. We're grateful for that. Okay. What's your level of confidence around potentially being able to initiate a registrational effort before the end of 27? That's next year. Pretty good. Pretty high. Yeah. Okay. Pretty high, yeah. Okay, yeah, I guess I've always kind of thought about this first update as being important, obviously, for a number of reasons we just discussed. Well, you don't get an oral presentation at ACR because you got shitty data, right? But it seems to me that the update in 27 that you mentioned, right, in terms of additional follow-up. Oh, yeah-yeah-yeah, no, look, I think we'll be able to tell you at the end of it, a little bit of a lack of trust right now around these patient deaths, not just with investment, but with the FDA, and we gotta make sure that we're doing the right thing and showing the safety profile. and so everybody and i think we all will and whether that's a manufacturing issue or just a rapid expansion a release of cytokines release of gamma interferon release of macrophages who knows what that is but that's going to be important for all cell types and i think where nk cells are going to come out is you're not going to see any of the hyperimmune syndrome because we don't have that rapid expansion in the patient and the release of all those cytokine and the icans and the cytokin release syndrome that comes to it with it that then releases the gammon and feron, the macrophages and all that stuff. So that's what we're hoping for NK cells, but the proof will be in the durability of responses and in the durability of the lack of these, you know, unfortunate toxicities, which are fine in oncology patients and may not be good for autoimmune patients. Understood. That's all we have for time. I know we're a bit over, but thanks. Thank you for coming up with. Yeah. Thanks for patching in. I appreciate it. Sorry, everyone for the technical difficulties and thanks for joining. Thank you.