Hello, everyone. Thank you for joining us for our Cell Therapy Autoimmune Panel. I'm Sam Semenkow, one of the biotech analysts here at Citi. I'm joined with my colleague, Yigal Nochomovitz, on the end. It's my pleasure to have with us today, Gwen Binder. She's President of Science and Tech at Cabaletta Bio, Pascal Touchon, CEO and President of Atara Biotherapeutics, and, Kevin Xie, CEO and President of Gracell. CFO. CFO. I'm sorry, CFO. I got mixed up. Yes. Well, thank you for all joining us today for what I hope will be a lively panel. So just to kick it off, perhaps we could just go down the line. If you could all give a very brief, like, one to two summary of your company and what you're working on. Yeah, thanks. Really a pleasure to be here. Cabaletta Bio is a clinical-stage biotechnology company. We're focused. Since we were founded in 2018, and since the beginning, we've been focused on developing targeted curative therapies for patients with autoimmune disease. Currently, our focus is in the CD19 CAR-T for broad indication autoimmune disease. We have two INDs open. The first is in lupus, with two cohorts, one with lupus nephritis and the other with non-renal lupus, and a second IND opened shortly thereafter in myositis, and to my knowledge, we're the first and only in myositis, which is a significant unmet medical need in autoimmunity. We have three cohorts there, one in antisynthetase myositis, the other in dermatomyositis, and then immune-mediated necrotizing myositis. We have given public guidance that we inftend to have initial data in the first half of 2024, and I'll stop there. So pleasure to be here. Atara Biotherapeutics is a leader in the field of allogeneic T-cell therapy for cancer and autoimmune disease, and we have three program in the clinic. But very importantly, we obtained the first-ever approval for an allogeneic T-cell therapy at the end of last year in Europe, with the approval of Ebvallo, first product that is now being launched by our partner, Pierre Fabre, in Europe very successfully. And that's an allogeneic T-cell therapy that is targeting some specific cancer related to Epstein-Barr virus, initiation. And we have allogeneic T-cells that are targeting EBV in the B-cells and eliminating these B-cells. The product has been used in more than 400 patients already, and as I said, it's approved, now launch in Europe, and it's going to be filed hopefully soon in the U.S., as we're discussing with the FDA about the timing of the filing of the BLA. Now, we have a second product that is, in fact, I would argue, the most advanced allogeneic T-cell therapy for autoimmune disease. That's a product called ATA188, that is in a phase II randomized, placebo-controlled study in progressive MS, called the EMBOLD study. That study with more than 90 patients, that is going to read out in early November. So in just two months time, we'll have a readout of that study in progressive MS patient, which is aiming at improving disability in MS patient. Again, it's an allogeneic T-cell therapy that is very specific to what we believe is at the root cause of multiple sclerosis, i.e., a latent infection with EBV. Then we're also developing a pipeline of allogeneic CAR-Ts that are relying upon the unique biology of EBV T-cells from healthy donors. We transform these cells to create allogeneic EBV CAR-Ts, and we have a CD19 program that has been already cleared for IND, going to start its first study in lymphoma very soon, and we are considering other studies. They all benefit from the same platform around allogeneic EBV T-cells coming from healthy donors that we are able to manufacture at scale, because we are at commercial stage already, at a very, very low cost, and the ability to create real value for shareholders. Thanks. Good afternoon. It's good to be on this panel. So Gracell is a clinical stage cell therapy company. We have three technology platforms. One is a FasTCAR, which is the next day manufacturer, autologous manufacturer platform. Two is we call TruUCAR, is allogeneic technology. Third, SMART CAR-T is our solid tumor program. We have five program in the clinical stage, collectively have t]reated over 100 patients so far. Until recently, the focus has been exclusively on oncology, and you heard about the top focus on the FasTCAR and the TruUCARs on the hem, and then SMART CAR-T solid tumor. Related to this panel, which is autoimmune, most recently, we have announced publicly that we're expanding our leading program, GC012F, which is a FasTCAR technology, dual CAR construct, BCMA CD19 into autoimmune space. We are planning to file the U.S. IND this year. At the same time, we have already started to enroll patients in China through our investigator-initiated trial. Great. Thank you for that. So I, I think there's a growing body of interest from both investors as well as corporates like yourself, and just the autoimmune cell therapy space. In particular, there's been a growing body of academic data as well, really supporting, in particular, CD19 CAR-Ts. Can you just talk about how that has shaped your development so far with, with your programs? I know that it seems like you all have a CD19, so I think that would be great to hear from you. Yeah, sure. Thanks for that question. So recently there have been 10 published reports from the investigator at FAU University, Georg Schett, using the FMC63 binder, which is what is in Yescarta and Kymriah, 4-1BB CD3 signaling domain, in CAR-T-cells that have been manufactured over nine days, and this has led in 10 patients. So it's seven lupus patients, two myositis patients, one patient with systemic sclerosis, and dramatic clinical results in all patients. So in myositis and the lupus patients, these patients have gone into full clinical remissions off therapy, and in the systemic sclerosis patient, that patient's disease progression has completely been halted. So this has shaped our clinical design because we have developed our own binder, which is fully human, but has the same binding affinity as FMC63, and our CAR has a 4-1BB CD3 zeta signaling chain. Our construct is functionally identical to this construct that was used in the Schett studies, which have very clear clinical proof of concept, with the one difference that we're a human binder, so that if we do, at any time, want to go back and give multiple infusions or retreatments, we can do it without having a preexisting immune response in the patients. Our manufacturing process is also substantially similar. This has allowed us to have a very efficient clinical trial design, which we might come on to later in the discussion. But in short, it has allowed us to open two INDs in parallel. The FDA is not requiring us to have safety data with our construct from the first IND before going into the second. In each of these INDs, we have multiple cohorts which we can enroll in parallel. So we have multiple shots on goal, five shots on goal, five indications, which we will be enrolling in parallel without a requirement for dose escalation. So that means a six-patient pilot study in any one of those first five indications, we can immediately then go and start talking with regulators about what a pivotal design might need to look like. So a lot of learnings from Schett. We're taking what we know works in autoimmune disease and advancing it as quickly as possible for the benefit of patients. I think our strategy was influenced by two aspects. I'll start with your question on CD19 CAR-T. We have this allogeneic CD19 CAR-T that is going to the clinic right now, and what we did here is to try to optimize an aspect that we believe is very important, which is the persistence of the cell, the allogeneic cells. We know that the EBV-T-cells, by definition, allogeneic EBV-T-cells are persistent. We know that from Ebvallo, first product approved, where it's persisting in patients that do not have an immunodepletion for a few months. We know that from ATA188, or MS program, where we have data showing that the cells are persisting up to 2 months after the infusion, again, without immunodepletion. We've seen that some early experience at MSKCC in lymphoma has shown that an allogeneic EBV CD19 CAR-T can be giving durable remission for up to two years without any issue in terms of the relapsing. At the same time, we have optimized our costimulatory domain with 1XX, one invented by Michel Sadelain at MSKCC, that is leading to less T-cell exhaustion, hence enabling more functional persistence of the T-cells. Last but not least, we are manufacturing the product in a way that maintains memory T-cell phenotype. Having the EBV-T-cells, 1XX as the costimulatory domain, and memory T-cell phenotype enable us to optimize all the way to have more persistent allogeneic cells coming from alpha goods. I would say the influence on our strategy came really early on with the MS program. In fact, the academic team in Australia that did the first-ever study with an autologous type of T-cells for MS, treated 10 patients in a phase I, and seven out of 10 had positive response in terms of improvement. You have to consider that we're talking here about progressive MS. A disease where, by definition, these patients are progressing in disability. They are declining with time. Here you have seven out of 10 that improve on disability. Now, we replicated that with an allogeneic program, ATA188, in our phase I. We have treated 24 patients, and over the one-year study, plus an open label extension, all the patients that we followed, we have only four out of 24 that progressed. I mean, 20 out of 24 either were stable or improved. In fact, seven out of the 24 improved, 13 stable, four progressed. That's unheard of in progressive MS, because the patient should be progressing with time, and here we have patients improving and in fact, all being stable. That's what we're doing in our phase II study now, and that's what it influenced that. Also last year, there was two amazing papers, one in Science, from a Harvard team, that shows very clearly that multiple sclerosis, an autoimmune disease, is caused by EBV latent infection. That is a real causal factor of the disease. Not the only one. You need also some specific HLA type, genetic profile, as well as some environmental pressure, but EBV latent infection is always the, the, the trigger. We believe it's also the driver of the disease, and we believe so also because there was another paper in Nature Medicine. We're talking about the influence of academic expert that shows how EBV latent infection is causing MS and driving MS. And in fact, it's related to molecular mimicry between part of the EBV virus and brain proteins. And they've been able to show in MS patient to find antibodies that cross-react against the EBV virus, but also against brain proteins. And there is a case of mistaken identity, where the immune system is being stimulated to attack EBV, and in fact, it's attacking the brain proteins. So now we're using that in our phase II study, and we have more than 90 patients enrolled. In total, we have treated more than 120 patients with a progressive MS, with this allogeneic T-cell therapy targeting EBV, with very acceptable phase safety, favorable safety, and again, in a phase I, 20 out of 24 patients having either improvement or stability of their disease. So we were influenced by the academic work, but we're pushing that further into real exciting data in an autoimmune disease. Yeah. Seems to be a theme. Kevin? Yeah, sure. The paper on Nature late last year obviously was very groundbreaking, and there's great news for the patients, that autoimmune disease is a large market, and the lupus, for example, is huge and immense, that the current standard of care does have very marginal clinical benefit, so compared to what the paper has shown. And so obviously that, you know, company, large and small, with similar program are either going into this field or thinking about going to this field. So the question is that, you know, whether CD19 is enough and how the durability will look like, how the safety profile will look like. So those are the questions that I'm sure that the market are waiting to see. So for us, our leading program, GC012F, with CD19 BCMA, so far we treated about 60 oncology patients, and mostly on multiple myeloma and also some lymphoma patients, so we have a lot of experience. But first we can look at that, you know, what does the BCMA can offer besides CD19? So, there actually has been studies, including Carl June's group, have had paper in 2016 that, suggesting there is a group of plasma cell antibody-secreting cell that can stay in the plasma for a very, very long time, maybe a lifetime, that over time can still trigger the immune system reaction. And, the BCMA obviously express on the plasma cell. Internally, we also have data to support that this group of antibody-secreting cells, a group of them are actually CD19 negative, but BCMA positive. So we strongly believe that in addition to the CD19, with additional BCMA is still target is going to potentially add clinical benefit to the autoimmune therapy. That's number one. Number two, on the safety, obviously, the lupus or other autoimmune patients have much lower safety issue tolerance compared with leukemia oncology patients, right? So for us, fortunately, we already have, you know, about 60 oncology patient data with very, very, let's say, tolerable safety profile. What does it mean? Means we haven't seen any ICAN neurotoxicity of any grade. We have mostly seen very low-grade CRSs, grade one, grade two. For example, one of the cohorts we have is a frontline, newly diagnosed multiple myeloma study that had a 16-patient cohort. 75% of those patients actually had zero CRS events. So those data give us a lot of comfort to extend this program into autoimmune. And that's number two. Number three, I mentioned, this is our FasTCAR Technology with fast manufacturing. What does it mean? It means that the manufacturing process is an overnight process, versus typically a days or weeks-long process. Obviously, that means faster to get back to the patients and that offers multiple benefits, both therapeutically and economically to the patient and the healthcare system as a whole. So we're very excited to get that program going. I mean, it's already started enrolling patients in China. We're filing the U.S. IND this year. So, you know, hopefully we'll be reporting some exciting data and bring some good news to patients. So Kevin, you kind of touched on my next question in terms of specific design considerations for autoimmune-based cell therapy, mentioning the, you know, less tolerance for side effects, for safety. Could the panel expand on that? What are the other specific design considerations when thinking about an autoimmune-based cell therapy? And what are the challenges to developing an autoimmune cell therapies as opposed to where everyone's got a lot more experience in oncology? Maybe you can start with two aspects of our experience since we've treated more than 120 patients now with autoimmune disease. One aspect is with ATA188 in MS, we don't need lymphodepletion. There is no pretreatment. So five to 10 inside view of the cells, and then one to two hours monitoring, that's it. So the patient can be treated in outpatient clinic. But also possible because of the safety, as you said, overall safety is very important there. And we will have a different type of profile when you use different type of cells in autoimmune patients compared with oncology. What we've seen in progressive MS is that the safety is very favorable. We didn't have any particular reaction there. As I said, more than 120 patients treated already. And again, we have repeated treatment because in our possible administrations, we are testing cycles of administration that are repeated once a year. We have some patients that have been treated more than four years now in our phase one study, and still no safety, major issues, and maintenance of the efficacy part, as I mentioned earlier, that the patients that were stable are still stable four years later. The patients that were improved are still improved four years later... except one case of relapse. So that's really something important about the ability to optimize the regimen of administrations, ideally, if it is possible, with no pretreatment, with a simple to administer drugs. The other aspect is that you are dealing with physicians that are not used to cell therapy, and when we started a program with neurologists, it was a new thing for them. They were not used to use cell therapy, but now they're used to it, and we have more than 40 sites that have been exposed to the use of 81, 88, and they're fine with it because they're easy to use. It's no different from a monoclonal antibody. In fact, it's easier if you use Ocrevus. Remember Ocrevus in MS, it's a four to five hours IV with a lot of surveillance as well of the patients. Here, it's just five to 10 minutes bolus of cell, that's it. So that allows neurologists who are not used to use cell therapy in an autoimmune disease, neuroautoimmune disease, to get comfortable with it. And now they're fine. They don't see an issue with the use of cell therapy. So, safety, to be able to make sure that you monitor that, ideally try to limit your volume for depletion, and the ability to train and get the physician comfortable with the use of this cell therapy that ultimately should be used like monoclonal antibody. It shouldn't be any major difference there. Of course, there's a difference in logistics. Storage is pretty easy. You ship that within three days, it's delivered to the patients, but still they need to have somewhere where the cells are being cryopreserved. Then you just fill the cells and then infuse that. Again, the simplicity of administration, the safety, and the ability to make sure that you limit any type of pretreatment or depletion, is key for autoimmune disease. Mm-hmm. Yeah, I would agree with most of those points. I think, you know, definitely the bar for safety is far higher, and the ability to go without lymphodepletion is a very attractive feature of your technology. But, when you look at the wider population of autoimmune disease that's potentially targetable by CD19 CAR therapy, when we talk to physicians, a single round of Cy/Flu, which is the current preconditioning, that it has been shown to be successful in the German studies, is something that the investigators are very comfortable to do in order to put their patients into a long-term remission off therapy, especially for many of these patients that have seen prior treatments, or for patients, like many in myositis, that don't have any therapies available to them at all. So I definitely agree with that simplicity of the one infusion and leading to long-term durable results. Safety, safety, safety, you know, for us, selecting a binder that is fully human has been also shown not to have neurotoxicity. CRS, the 4-1BB co-stimulatory domain, also shown across multiple in vitro studies. And also, if you look at Yescarta or Kymriah out on the market, Yescarta usually needs inpatient dosing, and Kymriah usually can be done outpatient. So this is really due to CRS. So this is really the safest profile we can use. Are there some indications, some autoimmune indications that are more suitable for cell therapy? Are there ones that you would avoid for certain reasons, or is the field open as long as you can target the B-cells, then anything is- Anything, you can go for anything, or are there some limitations? Yeah, the field has really expanded in our understanding of the role of B- cells in driving autoimmune disease. So, if you ask yourself the question, why is targeting B-cells effective in autoimmune disease? I mean, in multiple sclerosis, maybe there's a thesis about the role of EBV and molecular mimicry, but even more broadly, in autoimmune disease, B-cells, we are coming to understand, are really a driving force of not just the autoantibody response, but also the T-cell response. So it's known that you can have autoantibodies present for a long time before you even have any clinical manifestations of disease. So in many diseases, the autoantibody, in fact, is a biomarker, not actually a pathogenic mechanism. In some, it's a pathogenic mechanism. So when you deeply deplete B-cells in patients, what you're doing is you're removing the driver of T-cell-mediated autoimmunity. If you deeply deplete, like all the way, you know, in all the secondary lymphoid tissue, which is something that antibody-mediated therapeutics can't do, you then get a rejuvenation of naive B-cells that are not autoreactive and then, therefore, do not drive the T-cell response. And so nobody had the courage to actually try this approach until it was done in Germany, under their compassionate use opportunity, which is codified in their law. And now with this data, now it's really opened up a huge part, a huge field of autoimmune indications that is far larger than anything we imagined in the oncology space. I agree. I think it's going to be pretty large, the field of application. Safety will be the key to know whether you can go, because there will be- It's, I mean, some of the autoimmune disease, think about lupus, are extremely diverse, the whole genome. So how the patient will react from an efficacy safety point of view is still unknown, and we need to have all these experiments that we are conducting there. But I will add also that how you specifically target some B-cells could be important. Like with ATA188, we're targeting the EBV-infected B-cells. The possibility to also attack plasma cell, because you have some of these long-term plasma cells that are producing antibodies, and we have that, for example, with a product, which explain why we believe that we have a better efficacy than anti-CD20. Because anti-CD20 will not eliminate plasma cell. We can eliminate plasma cell. Also, the tissue specific aspect of the disease, like in MS, we believe that one of the key issue is the B-cells infected by EBV in the brain.] We know that antibodies cannot cross well the blood-brain barrier. That's why ocrelizumab and others do not have so much efficacy in non-active progressive MS. And here we have the cells. We know that they cross the blood-brain barrier, they act in the brain, and they can eliminate these B-cells in the brain. So there might be some other aspect of autoimmune disease, where if you want to have some tissue-specific elimination of B-cells, T-cells, it could be extremely effective in that aspect. Andrew has a question, I believe. Do we have a microphone? Thanks. I share your enthusiasm for the Schett data. It was eye-popping in a way that few data is. When I saw it in Germany, presented about four months ago, maybe a bit longer. But there's lots and lots of questions. So from a regulatory perspective, you're dealing with the Cell And Gene division, and it begs questions about control arms, basket trials, duration of follow-up. Novartis and Bristol, I think, are just having these conversations now. But I'm curious if you've got any thoughts about what the likely development protocol is gonna be to bring these drugs to the market in the U.S., given we have this very unusual setup. The second question is on preconditioning, which is acceptable within an oncology setting, but in a refractory autoimmune setting, if you don't need it, maybe you don't. I'm curious whether you think we need it and what we know. And then the third point you touched upon briefly was, what's the correct cell type? So EBV and vector cells, you know, is kind of a sweet opportunity. But you also referenced eliminating plasma cells, so BCMA, CD20, CD22. So, you know, yes, we've stumbled across CD19, but is that the right opportunity? And then the final thing, so there's four, and I'll remind you if you lose track, but the fourth one is supply chain. So you have two guys with very big guns and lots of capacity who are blazing the route here. And while you may have interesting cell constructs, it's gonna be a race. So how do you participate in that? You presumably need a partner, a manufacturing supply. Do you hope to hook up with J&J, Lilly, Astra, Roche? What's the appetite? I know from my conversations, many of them are holding out for allogeneic cells rather than diving in for autologous. So I'm just curious. So there we go. There we go. I warned you those are gonna be a shopping list. You can take whatever of those resonates the most. That's great. Yeah. So, these are, you know, questions we've been receiving over the last couple of days. And so, you know, thank you for asking them. I'm sure many people have this, in mind. I mean, first, regarding the development protocol, and we at Cabaletta think that we have a very unique and competitive development approach. I've been working in the field of engineering T-cell therapy since before any pharma was interested in it. I wrote the original CD19 CAR IND, and I've had multiple interactions with regulators on innovative cell therapy, clinical trial designs, and there's many ways to approach this. The way we have decided to approach this is individual INDs for each indication with multiple cohorts, so we have maximum flexibility in being able to take a particular subtype forward. As I mentioned earlier, each of these are six-patient pilot cohorts without the requirement for a dose escalation, because we are able to draw from the compelling data from Germany and basically say, "Look, our com..." And we tested it, and we presented this at ASGCT, is the comparability of our product to the Kymriah construct, basically, which is basically what the Schett group used, with a slight difference in the transmembrane domain. That's the rapid clinical trial development approach, and if, well, we're not commenting on clinical, you know, later-phase clinical trial designs. You can draw from oncology. If you look at, you know, for example, what Kite did in their Yescarta development pathway, they converted an early phase to a late phase clinical study. Okay, I just- And maybe on that, I mean, we have an interesting level of interaction on the CD19 allogeneic CAR-T, which is more on safety because of the allogeneic part of it and so on. And that's understandable, but we were able to clear the IND for in lupus, and therefore, we can move forward. But with ATA188, where we've treated more than 120 patients with an allogeneic T-cell therapy in progressive MS, at the beginning, there was a lot of question about the product and the safety. Now that we have that safety database. This is a different type of discussion. We're also running now a placebo-controlled study, which is, to my knowledge, the first-ever placebo-controlled study in cell therapy in an autoimmune disease, and that's going to be out in November. Mm-hmm. The FDA was very, very, nice to us to support us, and they gave us two Fast Track designations for ATA188, one in PPMS, one in SPMS. For that reason, that they're already thinking with us about the phase III and how do you go to phase III with that type of program. So I would say the ball is starting to roll with the CBER in terms of thinking about pivotal development in autoimmune disease or for cell therapy, a bit in allogeneic. And maybe on your last questions, I mean, allogeneic, we believe, is the key there because we already scaled. We know that we can make thousands of doses with one leukopak. In fact, our aim, and we have the data to show that once we are at pivotal commercial stage, is to make up to 20,000 doses from one Leukopak. So the product is there in inventory, available for use, so there is not so much of an issue in terms of the scalability and certainly logistical supply. And we've treated with all the product plus ATA188 in both cancer and autoimmune disease, more than 500 patients worldwide. We deliver that within three days to the site of treatment. It's treated in outpatient clinic in MS by neurologists that are pretty used now to use cell therapy and to treat. That is even easier to use than ocrelizumab in MS. So, my question about the supply chain is really geared towards the autologous. Obviously, it's much easier with allogeneic. But since you asked that, I'll stop here because it's these guys' panels. Could you talk to, from a autologous approach, why you are hesitant about the allogeneic alternative which your colleagues are exploring? Sure. Yeah. I mean, we're interested in bringing this transformative therapy to patients as quickly as possible. We never stated that we're hesitant about an allogeneic process, but this autologous approach works in patients with autoimmune disease, and it's commercializable, to a certain scale. I think scale will be a challenge, as we go very broadly into autoimmune disease, but that is not our main focus at this company, is to be first to launch with the CD19 CAR, and that's with an autologous therapy. We have the opportunity to do that with our SLE and myositis studies. That doesn't mean we're not, you know, thinking about what other modalities or how can we increase scale with our current modality, and those are very active, active things. Right now, in terms of manufacturing, we realize we're a smaller company, but we have been thinking about how to supply commercially for the last, you know, five years of our operations. We have plans to build our own facility, and we are also, of course, looking at, you know, potential strategic partnerships in order to get that global footprint as well. And so we're very confident that we will be able to launch the first, curative targeted cell therapy for patients with autoimmune disease in an autologous form. And then there are- You know, there's a big field and many steps after that to continue to increase capacity, maybe consider allogeneic, maybe consider other approaches as well. I'm not sure if that is a satisfying answer, but I think for us, our eye is on getting this to patients who really need this therapy as quickly as possible, and I believe we can do that. I want to make sure I give Kevin an opportunity to respond to anything. Sure. So Gracell has both autologous and allogeneic platforms. Under each platform, we have multiple programs, and obviously, the benefit of allogeneic is there, right? That Pascal elaborated clearly, that's why tons of capital has been pouring into this field, and we have experience on both. So at the end of the day, it's the end result of the patients, it's efficacy and safety. So in our experience, you know, for example, the percentage of CRs from allogeneic program versus autologous, there's still a gap. The safety in terms of CRS is that, you know, we have consistently seen much better safety profile from autologous for the reason I think, you know, that's a much bigger discussion in terms of rejections and all the others and what other you need to use. So the bottom line is that, right now, autologous still give the best efficacy and the safety profile to the patients, and that's why that's being used now. So coming back to the earlier few questions you mentioned. In terms of the pretreatment, we're using exactly the same pretreatment regimen for our investigator-initiated trial, lupus right now, as we use for multiple myeloma, which is two rounds of Cy/Flu. Why we're doing that? Because we already have 60 oncology patient data that's generating very consistent, tolerable safety profile. So that's a good starting point for us to have. We're starting with the same dose, which is one times 10 to the fifth per kg, so it's about 1 million cells. This is a good starting point for now, and certainly, we would want to have ideally not having even less lymphodepletion cycle, or even resolve lymphodepletion cycle. But for us, because of the experience we have had, that's a good place to have, a good place to start. Manufacture-wise, you know, Lonza is supporting us in the U.S. for phase I, and the fast manufacture process we have, which is a two-day process in terms of the time taking the clean room, is a huge advantage to not only lower the cost overall, but also bringing the capacity utilization to a much, much more efficient level. We think over time, it's going to yield significant economic benefit for both the company and also to the healthcare system. Great. I think in our final minutes, maybe we can squeeze in one company-specific question for each of you. So perhaps I can start with you, Gwen. Can you- You're gonna have your initial data in the first half of 2024, and it can come from any of the five cohorts that you've spoken of, and potentially more than one patient from some cohorts, depending upon enrollment speed. Can you just talk about what we should be expecting from you in terms of like, actual data? And if you can also just tag in on your manufacturing process you recently just announced with WuXi. Is that your commercial process or is there still more work to be done there? Gotcha. Gotcha. Thanks. So we've given public guidance that we will announce initial three-month data from our three-month data from patients in the first half of 2024. That data, if you look at the Schett paper, will be similar to that. We're looking at clinical and serologic markers of response, and also we'll be looking at typical data as we've presented from our prior cell therapy studies in autoimmune disease, which we've been conducting over the last three years. We've treated over 16 patients in the dose escalation study. That has been published over time. You can look at some of the correlative type data. We also just published Tuesday, actually, a collaboration with Professor Georg Schett. We expanded on his analysis of autoantibodies and cytokines and also vaccine responses. So we'll be looking at all of those things, whether or not that will be in the initial data package. You know, you know, we're not giving guidance on that, but that can give you an idea of the type of science we're doing with our clinical trials, and also the depth of collaboration and insights we're continuing to get from those, patients that are way, you know, that are ahead of the curve, with now about 2.5 years of follow-up, and still in clinical remission. Regarding manufacturing, we have 100% manufacturing success, from the studies we've been conducting, over the last 3 years. We have expanded into a commercially compliant CDMO, WuXi, which you referred to. We have manufactured clinical lots, also 100% success there. The current process will need some additional changes. We're thinking about that, things that are very standard in cell therapy and not dramatic changes, such as closing certain steps of the process and so forth. And those are things we're well ahead of the curve on and would implement ahead of a pivotal study. Wuxi can supply globally, so again, it can support additional sites in Europe, the U.K. and elsewhere, as well as the United States. You know, in the interim, until we get to Stage 3 of our manufacturing strategy, which is our own facility and potentially a strategic partnership. So thank you. Thank you. Pascal, you mentioned the EMBOLD data in November for ATA188 and progressive MS. Can you just talk a little bit more about what you want to see from the full data readout, and what would be considered a clinically meaningful result on EDSS improvement? Yeah. So we are on track to have the readout on our primary criteria in that study, called the EMBOLD study, which has enrolled more than 90 patients. That will be available for readout early November, half placebo, half active. And the primary criteria, which was aligned with the FDA, not only for that phase II study, but also as a potential rational pivotal study type of criteria, is confirmed disability improvement at 12 months. Confirmed means two consecutive time points, so it has to be at least nine months and 12 months. Patients are evaluated every three months. And it is disability improvement measures by EDSS, which is the validated scale used for any type of regulatory approval in that particular space. These are progressive MS patients, or more specifically, non-active progressive MS patients, which are the vast majority of progressive MS patients, do not have relapses, are not active, don't have active lesions. We're focusing on that medical need that is completely unmet because there is no approved therapy today in the world for non-active SPMS, and it's just in the U.S. where Ocrevus has been approved for PPMS, and, and including the non-active part. So it's very limited amount of therapies today, an unmet medical need that is very clear, and we're looking at confirmed disability improvement, not only delay in progression that the others have done. But we'll have data on that 12-month confirmed disability improvement. We'll also have data beyond 12 months, because in our protocol, the patient also followed beyond 12 months. So we have some patients that will have achieved 15, 18, 21, 24 months. That will be important to see whether disability improvement further improve with time, and whether we can maintain stability also in other patients. Because we believe that the benefit of the product could not only be a percentage of the patient being improvers, which is something very, very new, a change of paradigm in the treatment of progressive MS, but also some patients just being stable, which by itself is a benefit, a transformational benefit, as no treatment today is able to stabilize patients and, of course, to improve patients. We'll have a battery of biomarkers, both imaging biomarkers, MTR, MRI, as well as a number of fluid biomarkers available, and that will be disclosed in terms of data early November. Now, based on that, we think that we will have a lot of potential next step. One of them could be to go to phase III studies, and we've already discussed with the FDA. We need to discuss again with them and EMA there. But also to further understand how the product can benefit different type of patients within progressive MS and be maybe beyond progressive MS. So that's a very exciting catalyst for us. And before that, we will have important catalysts also coming on T-cell on our most advanced product, that, as you know, is already approved in Europe under the name of Ebvallo and being launched by Pierre Fabre. We are finalizing a discussion with the FDA to be able to give some new guidance on the timing of the BLA, that we expect to be relatively soon. At the same time, we're actively negotiating with potential partners for a U.S. commercial deal. So ideally, we would like to see clarity with the FDA, announcement of a deal that will help us to reduce our cash burn and improve our cash runway, and then the EMBOLD readout over the next two months. So most exciting two months ever for the company are starting now. Kevin, for the China IIT, for the lupus study, tell us about- I think the data is next in 1H 2024. Can you tell us what would constitute proof of concept there? And do you want to see that proof of concept before you submit the IND here in the United States? I answer your last question first. No, we're not waiting for the IT data to submit the U.S. IND. This IND, once again, the construct is identical to our oncology study, so we already have that IND cleared by the FDA in terms of the CMC sections, identical, the toxicology is the same. So that is in the process of submission. At the same time, the China IT obviously is going to give us additional insight on the real, you know, patient response. We have enrolled about a handful of patients. The goal is to enroll about 10 patients, potentially double digit. So come to the first data readout, first half of next year. What you'd like to see is, you know, some patients have had nine months, even some patients—definitely half of the patients will have, I would say, six months follow-up time, and some of them may even have nine months follow-up time. Some is relatively early, maybe just had a three months follow-up time. So the key metrics we're going to report is the same as with, you know, all the other trial in terms of safety, and the efficacy on the SLEDAI score system. I think when more companies start reporting data, people will start to look at more details, obviously, in terms of patient baseline, how young and old, and where the SLEDAI score starting from and all that. I think it will be a lot more information for the market to digest in the next six to 12 months. Yeah. Yeah, definitely. Sounds like a lot of really great data in the next six to 12 months. Well, thank you. That's our time. Thank you so much for being here. It's been a pleasure to have you all up here with us. Thanks. Thank you very much.