Good morning. At this time, I would like to welcome everyone to Cabaletta Bio's conference call and webcast. Currently, all participants are in listen-only mode. After the speaker's remarks, there'll be a question and answer session. Please note that this call is being recorded and is the property of Cabaletta Bio. Unauthorized recording, reproduction, or transmission of this call without the express written consent of Cabaletta Bio is strictly prohibited. I would now like to turn the call over to Will Gammick of Precision AQ. Please proceed. Thank you, Michelle. Good morning, everyone, and thank you for joining Cabaletta Bio's conference call and webcast to discuss initial clinical data from the Phase I, II RESET-Myositis and RESET-SLE trials that was presented at EULAR earlier today. Before we begin, I encourage everyone to go to the investors section of our website at cabalettabio.com, where you can find the press release and slides related to today's call. I would like to remind everyone that we will be making forward-looking statements which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and their actual results may differ materially. Please review the risk factors in our SEC filings for additional details. We will begin the call with prepared remarks by Steven Nichtberger, our CEO. Iain McInnes, the Muirhead Chair of Medicine and Versus Arthritis Professor of Rheumatology at the University of Glasgow, will provide an overview of the current landscape for autoimmune diseases and the unmet need. Then David Chang, our CMO, will review the results of the initial clinical data presented at EULAR in more detail. In addition to the previously mentioned speakers, Gwendolyn Binder, our President of Science and Technology, and Anup Marda, our CFO, will join for the question and answer portion of the call. With that, I'll now turn the call over to Dr. Nichtberger. Thanks, Will, and thank you everyone for joining us today. We're excited that we had the opportunity to share initial clinical data from our RESET-Myositis and RESET-SLE clinical trials evaluating CABA-201 earlier today at EULAR. By way of background, CABA-201 was specifically designed for patients with autoimmune diseases. It was intentionally engineered to be similar to the academic 4-1BB costimulatory domain containing CD19 CAR T, evaluated by Dr. Georg Schett and his colleagues, which has generated transformative outcomes for patients with a variety of autoimmune diseases, igniting interest in the field. Not all CAR Ts are created equally. CABA-201 contains the identical signaling and 4-1BB costim domains as the academic construct, with a fully human CD19 targeting domain that binds to the same epitopes on the CD19 antigen as the murine FMC63 binder utilized in the academic studies, with the same biologic activity. CABA-201's binder has demonstrated a favorable safety profile when evaluated in approximately 20 oncology patients as a dual CAR with no ICANS observed and less than a 5% risk of grade three CRS in cancer patients. The key questions we intend to address today include, 1, is the initial safety profile of CABA-201 consistent with the academic construct which inspired our design? Specifically, what is the incidence and severity of CRS and ICANS? And two, is the initial CAR T cell expansion and B-cell elimination profile for CABA-201, as well as the serologic, translational, and clinical data, consistent with the academic clinical data, supporting the continued use of the selected dose of CABA-201, which is identical to the weight-based dose used in the academic studies? Next slide. CABA-201 is being studied across a broad range of autoimmune diseases within five disease-specific, company-sponsored INDs in lupus, myositis, systemic sclerosis, myasthenia gravis, and pemphigus vulgaris. Today, we're also pleased to announce the incorporation of the juvenile myositis cohort within the myositis IND for CABA-201, which we believe is the first company-sponsored clinical trial evaluating cell therapy and autoimmunity for a pediatric population. This builds on our previously announced success, gaining a rare pediatric disease designation in juvenile dermatomyositis earlier this year. There are now 10 independent cohorts, each with six patients able to be enrolled. Based on completed enrollment in any one cohort, data permitting, we expect to engage in discussions with FDA regarding design of potentially registrational trials for one or more of the cohorts. In addition, inspired by a clinical publication from one of our scientific founders, CABA-201 is being evaluated without a preconditioning regimen in an exploratory study. The early safety and activity data from the RESET clinical program inspired us to initiate the RESET-PV sub-study of CABA-201 without preconditioning.... now at up to 10 active clinical sites that are considering integration of the protocol amendment to the ongoing DesCAARTes trial. Today's presentation focuses on initial clinical and translational data from the RESET-Myositis and the RESET-SLE trials, which we believe support a promising safety profile consistent with the academic experience, as well as a promising activity profile consistent with the academic experience, supporting the use of the selected dose of CABA-201 at 1 × 10^6 cells per kilogram, which is the same dose used by Professor Schett's group with their similar 4-1BB containing CD19 CAR-T construct. Next slide. The RESET clinical trial program currently has 18 clinical sites open for enrollment across four trials: lupus, myositis, systemic sclerosis, and myasthenia gravis. Following a relatively modest start to the year, we are seeing enrollment ramp up, with five patients now enrolled across the program, including three patients enrolled over the last two months. As we move into the second half of 2024, we believe the initial clinical data presented today on CABA-201, combined with an expanding network of engaged investigators with sites already open across the country, provide the foundation for accelerated enrollment in our clinical trial program. With that, I'll turn the call over to Iain McInnes, the Muirhead Chair of Medicine and Versus Arthritis Professor of Rheumatology at the University of Glasgow, to provide his perspective on the treatment landscape for autoimmune diseases. Iain? Thanks, Steven. What a pleasure it is to be joining you today. I don't know how many of you are in the virtual room. I've just come across the road from the EULAR Annual Congress, addressing nearly 4,000 people in the rheumatoid arthritis plenary session. So it's nice to sit back and relax with a convivial company. So look, what an exciting time it is for us in the field of immune-mediated inflammatory diseases. Actually, the last time I remember this level of excitement was around the introduction of the biologics, the original TNF inhibitors, a couple of decades ago. And we've, of course, seen so much change in that time. We've, we've seen new medicines come along, we've seen consolidation in the field, but that does not mean that we've solved the problem. Ladies and gentlemen, despite the extraordinary progress we've made, we have significant unmet needs. We do not achieve remission nearly often enough, and that remission, once achieved, has to be maintained by the ongoing therapeutics. These are expensive therapeutics. They're also therapeutics that carry their own risks of toxicity, of intolerance, and frankly, the inconvenience of often young people, because many people with immune-mediated diseases we're talking about are young, and they have a lifetime ahead of them. Of course, the other implication of that, well-known to you all, is that young people with chronic disease impose huge healthcare burden, costs on themselves, their family, costs on society, costs on the healthcare providers. So we, as a field, are rapidly seeking solutions that allow earlier intervention, if you like, disease interception, or in those with established disease, profound interventions that allow us to reestablish a state of so-called immunologic homeostasis. That is a state of balance in the disordered immune response. So today we're thinking mainly about SLE and myositis, two of a number of autoimmune diseases. By the way, if you're interested, the autoimmune disease prevalence is rising. We just reported last year on 22 million people in the U.K. Biobank databanks, increasing prevalence of autoimmunity over 20 years. So this is a challenge that is set to grow, not diminish. These are particularly challenging disorders, lupus, myositis, and the need here for drug-free, long-term, durable disease remission is absolutely imperative. Let's think first of all about myositis. Only one FDA-approved therapy in one subtype, that's IVIG in dermatomyositis. Think of that against the whole range of mechanisms of action we have available in rheumatoid and in psoriatic arthritis in the axSpA spectrum. It's a stark contrast. IMNM, the necrotizing variant, considered one of the most refractory subtypes, where patients are often resistant to standard of care, including off-label IVIG and/or other B-cell targeting agents, rituximab being the most commonly applied. Lupus. Systemic lupus erythematosus, the disease of the wolf, a disease of multiple tissues, a disease that is devastating its impact on disadvantaged people, particularly in young people, more often women than men. 40% of people with lupus will go on and develop life-threatening target organ disease, lupus nephritis, for example. But remember, it's a disease that is no respecter of tissue boundaries, lungs, brain, skin, joints, reproductive possibility, and an enriched life beyond them. 25% risk of death within 10 years in the lupus nephritis cohorts. And sadly, incomplete responses, despite the advances of immune-targeted therapies in the last year or so-... Take all of that together, the clinical challenge is very clear: we need durable, effective, safe therapeutics that reestablish immune tolerance, that homeostasis that has eluded us thus far, to eliminate the need for long-term therapy. Next slide, please. So the recent academic experience from my, my friends and colleagues over in Erlangen, Georg Schett and his colleagues with CAR T therapies directed to CD19 in autoimmune disease, has given a potentially transformative signal in the way in which we may treat these diseases. Academic data from the Erlangen group that has now tested over 20 patients in lupus, myositis, and systemic sclerosis, has demonstrated the ability to deliver drug-free, complete responses that are durable and reliable in those patients, with thus far, a favorable safety profile. As a living therapy, CAR T-cells have shown the ability to achieve deep B-cell depletion in the periphery, as well as in the relevant secondary lymphoid organs, where B-cell derives. That's a key differentiating feature from our previous attempts to target the B-cell compartment in immune disease. And achieving this systemic B-cell depletion, not just in the periphery, is critical to enabling an immune system reset. So while chronic therapies such as monoclonal antibodies or even bispecifics may have the opportunity to provide benefits for patients with autoimmune diseases, with chronic dosing, to date, have not yet shown that any other modality beyond a target CAR T treatment has the ability to deeply deplete B-cells in all tissues, lymph nodes, lymphoid organs, likely the tissue origins of autoimmune disease, leading to an immune system reset and a drug-free, durable, reliable, complete response. So excited by the initial clinical data for CABA-201 to provide a first look at the safety profile and clinical activity of the CAR T CD19 construct. So with those general remarks, it's a pleasure to turn over to David from the Cabaletta team, who will give a more detailed review of the initial data presented at EULAR. David? Great. Uh, thank you, Iain. Next slide, please. So our Phase I, II RESET myositis trial for CABA-201 in myositis is designed to evaluate a single dose of CABA-201, following preconditioning with fludarabine and cyclophosphamide at typical doses, the same doses that were used in the academic studies. There are three independent parallel enrolling cohorts in the study: immune-mediated necrotizing myopathy, dermatomyositis, and anti-synthetase syndrome. Each of which can dose up to and over six patients, in addition to the pediatric cohort, which has been recently added to the study. The key inclusion/exclusion criteria are listed on the left part of the slide, and the primary endpoint of the study is the incidence and severity of adverse events up to 20 days post CABA-201 infusion. We are also evaluating several clinical and translational markers of disease activity as secondary endpoints in the study. Next slide, please. Our RESET-SLE Phase I, II trial for CABA-201 in lupus is designed to be similar to our RESET-Myositis study. We aim to evaluate a single dose of CABA-201 across the Phase I, II RESET clinical trial program, without a dose escalation requirement, following typical preconditioning. There are two independent cohorts in the lupus study, the non-renal SLE and the lupus nephritis cohort, which includes biopsy-confirmed Class 3 or Class 4 lupus nephritis, each of which can dose six patients or more. Key inclusion and exclusion criteria are listed on the left part of the slide, and the primary endpoint is similar to the myositis study, which is the incidence and severity of adverse events up to 28 days post CABA-201 infusion, while also monitoring clinical and translational markers of disease activity as secondary endpoints. Next slide. Prior to dosing any patients, we provided this framework for important parameters that we believe should be examined and assessed when it comes to the evaluation of any cell therapy in autoimmune diseases. To that end, we've provided the important criteria across translational, clinical, and patient experience metrics, that are intended to provide clarity to the interpretation of our initial clinical data. Importantly, we plan to report on all of these parameters for the two patients reviewed today, through the relevant follow-up period, with additional insights into timing of B-cell repopulation and B-cell phenotyping for the first myositis patient in our study. Next slide. So in this slide, the first myositis patient on the left column, you can see that his dose, for the immune-mediated necrotizing myopathy cohort in the RESET-Myositis study. He's a 31-year-old male with a 2-year history of disease, positive for the Anti-SRP antibody, and who had prior disease-specific therapies that included IVIG, rituximab, methotrexate, and steroids. The last dose of rituximab was approximately 8 months prior to CABA-201 infusion. On the right side, you see the first lupus patient dose is in the non-renal SLE cohort in the RESET-SLE study. He is a 26-year-old male with a 6-year history of disease, positive for anti-double-stranded DNA antibody, and who had prior disease-specific therapies that included cyclophosphamide, voclosporin, belimumab, tacrolimus, mycophenolate, hydroxychloroquine, and steroids. Both patients were treated with a single infusion, weight-based dosing regimen of CABA-201 at 1 × 10^6 cells per kilogram, following a pre-conditioning regimen of cyclophosphamide and fludarabine that was identical to that used in the academic study by the Schett and McInnes group. Next slide, please. CABA-201 was administered on the first day of a 4-day hospital stay, as currently required by the study protocol, and was generally well tolerated, with no serious adverse events, no infections reported for either patient through the follow-up period. There was no cytokine release syndrome and no immune effector cell-associated neurotoxicity syndrome, or ICANS, of any grade observed for either patient during their post-infusion, 28-day, dose-limiting toxicity observation windows. Tocilizumab was not administered to either patient. All chronic maintenance therapy or concomitant medications were discontinued for both patients prior to infusion of CABA-201 and through the follow-up period, other than a planned prednisone taper for the lupus patient. Next slide. In both patients dosed with CABA-201, the kinetics of CAR-T expansion and B-cell depletion was consistent with the initial patients reported in the academic studies. Peak expansion on the left-hand side occurred at day 15 post-infusion, which is also when complete B-cell depletion was observed in both patients, which you can see on the right side. The rapid contraction of the CAR T cells following peak expansion is suggestive of elimination of the target B-cells in the body. Next slide, please. B-cell depletion was sustained in both patients dosed with CABA-201 through the first month of follow-up, despite the recovery of leukocytes, as anticipated on the right side, after approximately 2 weeks- 3 weeks. This transient leukopenia is an expected effect of the preconditioning regimen. Next slide. As shown in the graph on this slide, the serologic and clinical markers in the first myositis patient with predominantly muscle symptoms related to the immune-mediated necrotizing myopathy, was dosed with CABA-201, demonstrated improvement while discontinuing all disease-specific therapies, and is consistent with the clinical data reported by Dr. Schett and his colleagues using the academic construct. Autoantibodies on the bottom left declined as expected, with the SRP declining, as well as SSA Ro52. The CK levels approached normal levels by three months, and the MMT-8 was starting to improve, consistent with academic data of another IMNM patient. On the far right-hand side, you can see the TIS, or the Total Improvement Score graph, demonstrating the clinical effects of CABA-201 during the first three months. And to facilitate comparison and put this into context, we've also included in the background data that has been previously reported on the clinical response from the myositis patients treated with the academic CD19 CAR-T product in gray. While the three antisynthetase syndrome myositis subtype patients, who had significant lung disease, demonstrated variable responses at three months, and by six months they were all major responders. More recently, as reported by Professor Schett earlier today, the first IMNM patient treated with the academic construct in the ongoing CASTLE academic study demonstrated a minor improvement in the total improvement score at three months, which continued to improve to a major response by 6 months, despite no additional therapies. We believe that taken together, these translational and clinical data demonstrate that the dose of CABA-201 we are using is replicating the data from the academic studies. The design of our recent clinical trial program with individual cohorts for each subtype of each disease should allow us to develop early insights regarding any differences in clinical responses for each of the myositis subtypes. Next slide. The first lupus patient treated with CABA-201. We are very encouraged by the early trends that we are seeing here. The early trends are showing improvements towards improvement across multiple components of the SLEDAI-2K, from a baseline of 26- 10 at Week 4, including resolution of the patient's vasculitis, arthritis, and hematuria. For a patient who had previously received disease-specific therapies, including voclosporin, belimumab, cyclophosphamide, tacrolimus, and mycophenolate, we believe it is important that these results to date were achieved with no administration of B-cell depleting therapies within 6 months of enrollment, as well as discontinuation of all therapies at infusion other than ongoing taper for prednisone 10 milligrams per day. Next slide, please. We are excited to share the translational data from the first myositis patient dosed with CABA-201, who illustrates both the tissue level effects of CABA-201, in addition to the repopulation of B cells at 2 months post-infusion. On the left side of the slide, you can see the interferon gamma peak prior to the peripheral CABA-201 expansion peak suggests that the CAR T-cells may be migrating to the tissues, where they demonstrate cytotoxicity against relevant CD19-positive target cells. The resultant B-cell depletion that occurs, observed on the right side of the slide, is then followed by a spike in B-cell activation factor, or BAFF, triggering the reemergence of B cells for that patient. Next slide, please. So based on the B-cell phenotyping assays conducted so far to characterize the B-cell repopulation in the first myositis patient, the data demonstrated a complete elimination of the B cells following a B-cell population, followed by repopulation, with a marked shift towards the emergence of early naive transitional B-cell populations, consistent with the potential reset of the patient's immune system. Confirmatory analyses, including single-cell B-cell receptor sequencing, is ongoing. By week 12, the patient's B-cell repertoire is beginning to gradually shift from the early naive transitional phenotype to a naive B-cell phenotype. We are encouraged by this initial data, indicating the potential for CABA-201 to deeply but transiently deplete the immune system in patients with autoimmune diseases. Now I will turn it over to Steven to conclude our presentation. Thanks, David. CABA-201 has been specifically designed for patients with autoimmune diseases and was engineered to be similar to the academic CD19 CAR T construct, which ignited interest in the field based on academic data from over 20 patients with autoimmune disease, including long-term follow-up for up to three years. We aimed to answer two primary questions with our initial clinical data at EULAR. One, is the initial safety profile of CABA-201 consistent with the academic construct which inspired our design? Specifically, what is the incidence and severity of CRS and ICANS? And two, is the initial CAR T-cell expansion and B-cell elimination profile for CABA-201, as well as the serologic, translational, and clinical data consistent with the academic data, supporting the continued use of the selected dose of CABA-201, which is identical to the weight-based dose used in the academic studies. Based on the initial clinical data presented today, we are encouraged by the observation of no CRS, ICANS, or infections of any grade reported through the follow-up period for each of our first two patients. On the dose selection front, we believe the pharmacokinetic, pharmacodynamic, serologic, translational, and clinical data that we've presented are supportive of the dose we're developing. Starting with the engineering of CABA-201, we have been focused on replicating the academic clinical experience at least as well as any other company in the industry. Excuse me. Today, we took an important next step to working towards achieving the vision of the company since it was launched in 2018, to develop and launch the first targeted curative cellular therapies for patients with autoimmune diseases. The RESET clinical trial program currently has 18 clinical sites open for enrollment across four clinical trials, lupus, myositis, systemic sclerosis, and myasthenia gravis. Following a relatively modest start to the year, we are seeing enrollment ramp up, with five patients now enrolled across the program, including three patients enrolled over the last eight weeks. As we move into the second half of 2024, we believe the initial clinical data presented today on CABA-201, combined with our expanding network of engaged investigators with an industry-leading number of sites open across the country, provides the foundation for accelerated enrollment in our clinical trial program. Next slide. In the second half of 2024, we plan to present additional follow-up data from these and other patients dosed in the RESET myositis and RESET lupus trials. We also plan to report the initial clinical data from the RESET-SSc and RESET myasthenia gravis trials, each of which are now actively recruiting patients. We really appreciate that you chose to invest the time with us today and want to close by expressing our gratitude to the patients enrolled in our clinical studies. Now I'll turn the call over to the operator to begin the Q&A portion of the call. Operator? Thank you. In the interest of time, please limit yourself to one question. If you have additional questions, feel free to return to the queue. Please stand by while I compile the queue. Our first question comes from Josh Zimmer with Cantor Fitzgerald. Your line is open. Great. Thanks so much for taking the question. I guess I just got one I'll ask for the Cabaletta team. When do you expect the other 3 patients who are enrolled to be treated? And what if you have 18 sites currently enrolling, how do you expect that to evolve over the course of the year? Thank you. ... Thanks. Excuse me. Thanks for the question, Josh. So, historically, you can see from ClinicalTrials.gov when each of the first two patients were enrolled in the clinical study, and dosing and the follow-up are subsequently reported today. So you can calculate, it typically takes us, as well as other companies who have similar requirements to post their information on ClinicalTrials.gov for their first patients, about 2-3 months to go from enrolling to dosing. And that's a fairly standard timeline. A lot goes into that, ranging from the need to make an appointment for apheresis, thus our interest in apheresis-free solutions, to the delay associated with scheduling around vacations or of the patient or the physician or holidays for the hospital. And so there, there's a lot that goes into those timelines, but that, that's the nature of the, of, of the approach right now. As to the way we expect it to roll out, I think, the answer is, we don't know, and, because nobody's ever done this. It is incredibly difficult, challenging, to get the rheumatology, the neurology, the nephrology, any medical specialist who manages these patients with neurologic or rheumatologic disease or dermatologic disease, to first of all, meet, second of all, trust, and third of all, desire to work with the hematologist, the infusion specialist, the oncologist who is going to do the infusion of the therapy. And managing the handoff of the patient from the medical specialist to the infusion specialist and back again, is a very complicated, logistically challenging task. That may explain why, despite major pharmaceutical companies competing with us for these sites, we lead the industry with 18 sites open in the United States. The talent of the team, honed for the 4 years before we ever in-licensed CABA-201 on our legacy portfolio, where exactly the same tasks were required to open clinical sites, gave us a window into how to do this really well. That explains why we have the number of sites open we do. We expect those site numbers to continue to relentlessly increase, not only for lupus and myositis trials, but for the newly opened scleroderma and myasthenia gravis trials. So we're gonna see more and more sites opening. We're going to apply the learnings and share the learnings from our clinical data with all of our investigators as soon as we can, through personal visits and engagement very deeply, allow them to share these data with their communities of referring rheumatologists and others. And all of this is gonna result in what we would argue is a setup for Cabaletta to be among the leaders in enrollment for autoimmune CAR T products in the industry. I don't know what that number is, and I don't have expectations that I wanna set. And frankly, I think if we did that, we would be gauging how well we guess as opposed to how well we did. Cool. Thanks so much, and congrats on the progress. Thanks. Thank you. Our next question comes from Yatin Suneja with Guggenheim. Your line is open. Hey, guys. Congrats to the team on the presentation and the data. Two questions for me. Could you talk about the response kinetic difference between the antisynthetase patient and the IMNM patient? I also noticed that the IMNM patient can achieve a max score of 70 on a 100-point scale, but the antisynthetase patient can go up to 100. Could you maybe also help us understand the nuance there? Thank you. Yeah. Thanks, Yatin, for the question. Maybe, our Chief Medical Officer, David Chang, can answer this. Yeah, so let me answer the second one first, and if you could just clarify the first question after that. But the second question related to the maximum. So on our slide, we showed the maximum total improvement score for our IMNM patients was approximately 70. And the reason behind that is it all depends on where patients start. So if they start at a mild disease level, there's less room for improvement. So it's an improvement score, it's not a final state score, such as achieving remission or low disease state. And it isn't a difference between antisynthetase versus anti-SRP, immune-mediated necrotizing myopathy. It's more dependent on where patients start at their baseline and how much room there is to improve. So when we did the calculation for that particular patient, knowing what the baseline was, we said, "If everything got better, everything got better, then that maximum score could only be 70, because the patient already started as a less severe state." But you can see that even with the Schett data, with his IMNM patient, that patient doesn't get up to 95, 99, 100, that the other three patients, the other two patients with antisynthetase syndrome patients are achieving. And maybe I'll just give you one example just to help you think about this: let's use one of the components of the TIS is Physician Global, and your maximum point is 20. One needs to get a 4-point improvement to get that maximum score. So if somebody's starting with a Physician Global of three, they're never gonna get that maximum score of 20. So you can go down the line with all the 5 components, 6 components, the 6 components and calculate that out, what's the maximum score you can get? So I think here it isn't the difference in disease phenotypes, more of the baseline disease activity, and it's that some may just take longer. So it's very possible in IMNM patients, there's a longer time to see that muscle improvement because they have such a predominant muscle disease, whereas in antisynthetase, part of it is driven also by the lung disease. Iain, you want to add something? Yeah, just to add to that, it's a more generic phenomenon. There's a common misunderstanding that the symptoms and signs that a patient presents with are directly correlated to immunologic activity. By corollary, you switch the immune system off, the symptoms improve immediately, but that, of course, is not what happens. There are target tissues that are damaged, and if you would like to reflect on history, we've been very familiar with tissue damage in the immune disease field for years. Think bone erosion and rheumatoid. Think unrecoverable renal function in lupus over the years. If you think about muscle for a moment, we all know that it takes time to rebuild muscle strength and muscle conditioning. Anyone who's been off their feet for a while or suffered a fracture will be well aware of that. So in fact, the logical prediction of the biology here, and remember, this is a really high-quality biology-driven intervention, so we should use the biology to help us understand the impact. The prediction is that there will be delay between immunologic restitution and actual functional recovery of a tissue organ. It's really important that we bear that in mind as we reflect now and reflect in future on what the CAR-T revolution is going to deliver. Thank you, David, Steven. Thanks, Ian. Yatin, were both of your questions answered? Yes, very helpful. Thank you. Great. Thanks. Thank you. Our next question comes from Kelly Shi with Jefferies. Your line is open. Hi, good morning. This is Yun, on for Kelly. Thank you very much for taking the question, and congratulations on the positive data. One question on the B cell phenotyping. I noticed that the markers that you used are slightly different from what Dr. Schett looked at, so assume you're going to look at the same, including class switching, for example, please? Thank you. Gwen, maybe you can take this question. She's our President of Science and Technology, Gwendolyn Binder. Yes. Thank you so much for the question. And that's a great observation. Yes, in our slides, we're looking at the transitional B cells, the naive B cells, whereas Professor Schett looked at IgD as a marker of naive B cells and then looked for that class switch. So he's looking at B cells expressing IgD containing BCRs or IgG containing BCRs. A very simple way of saying it, which represents whether there's antigen experience in the B cells. This patient that we're presenting today is unique. As David mentioned, the patient had experienced Rituximab about eight months prior to enrollment on the study. And so the frequency of those memory IgG expressing B cells was so low, the sensitivity of the assay could not capture those cells. But our assays could capture a little bit of those memory B cells by using the markers we use, CD38, CD24. So if you look at the graph on Slide 21, you can see that there's a small proportion about 4% as a red line shown in baseline, which represents those memory B cells. And then in the light blue are the transitional B cells, which as illustrated in the picture on the left-hand side, you can see that these are cells that are recently emigrating from the bone marrow and not antigen experienced. And in dark blue, the naive B cells, which are a little bit more mature but still not antigen experienced. And so what we see, as the B cells come back at week eight, is we see a complete loss of those memory B cells. We see no red line, and you see that the predominant population of B cells are those transitional B cells coming out of the bone marrow as the patient is regenerating the B-cell compartment. And that is also it corresponds, as David took us through, with the increased levels of BAFFs to support that B-cell reconstitution. And then you can see, at week 12, you start to get further progression into that naive B-cell compartment, as you would expect. And so we would anticipate, over time, we would start to get some memory B cells come back as we continue to survey this patient. But this data is wholly consistent with a deep depletion of B cells and then a regeneration of new naive transitional B cells. But as we move forward, we will continue to look at both these markers and also the markers -- we will continue to use the markers that Schett utilized in his studies as well. Does that answer your question? Yes. Thank you very much. You're welcome. Thank you. Our next question comes from Samantha Semenkow with Citi. Your line is open. Hi, good afternoon from you, Lauren. Apologies in advance for any background noise. Just looking at the expansion data, if we compare the magnitude of CABA expansion with the data that Schett has reported, it seems CABA has a lower magnitude of expansion and a later peak expansion date. But the efficacy data thus far, it does seem to be tracking in line with Schett's data. So I know obviously we're working with small numbers here in both data sets, but I'm curious if you have any hypotheses for why this might be the case, given both of the CABA-201 patients, they do look similar in their magnitude. And how are you thinking about the amount of expansion you need for CABA-201 in the context of efficacy and safety data that you've seen thus far? Thank you. Yeah, maybe we can answer this in two parts, starting with Gwen and then passing off to David for the clinical. Sure. Yeah, thank you so much for the question, and that's a great observation. So, maybe just looking at slide 16. So first, the magnitude of expansion for the IMNM patient falls squarely within the median of peak expansion observed in the case series published by the Schett Group. The SLE patient is a little bit lower peak expansion, and I believe that that is due to an overall lower level of leukocyte counts in this patient. If you look at slide 17, this patient had a pretty consistent and low level of leukocytes at baseline. And so we think that this lower peak expansion may be reflective of that. But just flipping back to slide 16, you'll see that even though it's a lower level of peak expansion overall, the percentages of CAR T cells is similar between the two patients, and this also falls within the ranges previously reported. Interestingly, as you noted, despite the peak being around day 15, which, as you noted, is a little bit later than the peak published in the case series with Schett, which is day 9, we do see this immediate drop in B cells in the periphery, so on the right panel there. And as David took us through on Slide 20, we are seeing this peak of interferon gamma early on, which indicates... So interferon gamma is produced when T cells are engaging with their target antigen. And so, that indicates that the B cells are, the T cells, the CAR T cells are actually active. They're engaging with the target B cells earlier than we actually see that peak expansion. And so this is why we believe that this reflects that the cells are actually going into the tissues and mediating that B cell cytotoxicity ahead of when we actually see that peak of the CAR T cells in the peripheral circulation. So the majority of the B cells that are being targeted in the body are actually in the tissues. So I will pause. Oh, the one last thing I will add here is that the one difference between our product and the Schett product is the Schett process was able to use fresh cells because they manufacture on site, they treat on site. Our cells are frozen, and so with fresh cells, they will be more able to immediately expand rapidly upon infusion to greater levels than with frozen cells. And that may contribute to a different dynamic on the actual timing of the peak, but it's very well established in the literature, and of course, all of the approved CAR T products are frozen. And our peak expansion is similar to peak expansion timeframes that you will see in, for example, multiple myeloma with the anti-BCMA CAR T. And the myeloma setting is much more similar to the frequency of target you would expect to see in healthy patients versus the peak expansion that you would see in leukemia and lymphoma, where the tumor burden is much higher and would drive a much faster expansion and peak. So our data is consistent with what we expect, and then again, the correlatives in terms of the cytokines and the cadence of B-cell depletion is consistent with a therapeutic that is behaving in a similar fashion to the Schett construct. And I'll turn it over to you, David, to talk about the clinical aspects. Yeah, and one thing I want to add to what Gwen had just indicated is that regarding the peak expansion timing that we're reporting at day 15, we actually didn't have a time point in between day seven and day eight and day 15, so it could have been earlier. But the discussion that we've had with Carl June, who's one of the developers of CAR T therapy in oncology 15 years ago, we spoke with him, and he said, "This-- yeah, this makes sense in terms of kinetics of a frozen product." So one thing we've done, everything we've done, we've done almost identical to what was done by the German group in terms of the dose, the pre-conditioning regimen. The one thing we didn't do was using fresh cells, but there was a reason behind that. The reason was because it makes the convenience, the flexibility, much more palatable for patients and sites, so that if you have a frozen product, in essence, you're allowed to let the patient and the site choose their time to do the dosing. So, this is the most likely explanation that has been confirmed by Carl June, that the onset of peak expansion occurring a few days later is not unexpected. I think there's a question that I just want to go back to regarding the expansion. If you look at the numbers, you see numbers of- ... 3.something% and a little bit higher. But we went back and looked at Schett's data, and in his first two myositis patients, the first patient, the peak expansion is 3.5%. The second patient, who relapsed, was 50-something%. So that doesn't really explain. The peak expansion is not necessarily the driver for patients actually achieving full immune reset. What it tells you is that there were cells that multiplied because it engaged with the target B cell. And that's what you want. You want the target engagement, you want the expansion reflecting that target engagement, then you want the immune reset, you want naive cells coming back. And the data we've seen to date confirmed that that's what we're seeing. So it isn't necessarily the peak expansion. I think we have to look at all the parameters, in particular, the complete depletion and the repopulation of naive B cells. Thank you. Our next question comes from Douglas Tsao with H.C. Wainwright. Your line is open. Hi, good morning. Thanks for taking the questions. Maybe, what I'm curious is, when interpreting this data or thinking about this data, how do you-- obviously, you've started to see very nice sort of, or similar results to the academic experience. I guess, you know, at what point do you feel confident to sort of use that data since they're sort of further ahead of you, both the number of patients as well as just the time course of treatment in terms of response rates and durability to inform your own development plans? And I'm curious, you know, you've had some success using the data from academics in terms of, you sort of help getting the FDA to approve your initial dosing. You know, do you expect, or how do you expect the agency to consider the data from the academic experience in terms of design and potential registration studies? Thank you. Yeah, thanks. Thanks, Doug, for the question. Listen, in 2022, actually 2021, when we first saw Professor Schett's publication of the first patient, we thought it was too good to be true. But we decided that we need to get into the CD19-directed space at risk, in a sense, knowing that if this worked, the original premise of our company was going to be aged. And so we invested ourselves in thinking about what the perfect product would look like. And we came up with the notion that there are very few things that have ever been developed with this level of clinical data in the first study. Think about how many other targeted therapies you've ever seen, where 15 out of 15 patients have not just a response, but a complete response, where that response is completely transformative versus everything else out there. So, where the number one safety issue was fever that can be managed usually with an antipyretic, you know, Tylenol or the equivalent. And in some patients, if they had a second day of fever, they would prophylactically use a dose of tocilizumab. That's the side effect profile for this complete response cohort. And so we asked ourselves, how could we improve on this? And the answer was not to manufacture it differently or to, you know, a fast manufacturing timeline to get the product back to the patient more quickly. That added more risk than benefit. The answer was not to change elements of the targeting domain. If we could, we wanted to target the same epitopes. And so we did, with a fully human equivalent of the FMC63 binder. It was not to try to change the costimulatory domain, because this was delivering data that was just really terrific. It was generational. And so we started there, Doug, with the idea that we need to imitate everything that this bold academic physician and his team achieved through replicating their product as closely as we could. We then approached FDA with data in hand showing that not only our structure and our epitope binding domains, but also our function, was comparable sufficiently so that we did not need to do a dose-finding study. In fact, if you dose find and try to go to a lower dose, you don't know if you'll get durability, so you're gonna wait two or three years to see if you have comparable outcomes. If you're trying to improve safety, what are you trying to improve? Fever? You're gonna get rid of the fever. Well, the fever is part of the mechanism of action. So I'm not sure either of those was viable, and we made that argument to FDA, and we came away with no dose finding required, which is a distinguishing feature of our company's program versus every other that we know of when starting an autoimmune-focused program with a novel chemical or construct. and so now your question is directed to, you know, okay, so you've leveraged the Schett data, very, you know, clever perhaps, and you've had great advantage from doing that. But the proof is in the pudding as to whether we've succeeded. Today, we took the first step on a long road to, demonstrating through data, not through our beliefs, but through data, that in fact, we are replicating the Schett data. We'll continue to hold ourselves to that standard, not that we are gonna have data that is as fabulous as his initial cohort, because I don't think anybody will.... we will have side effects, we will have failure to treat, effectively in some patients. And that's fine, as long as what we have is at least as good, if not better than any other company in the industry. And there's room for all of us, but I'd like us to be the best, and I'd like us to be the first. And to do that, we rely not on what we need to do data-wise going forward, which of course, is necessary, but the design of our clinical program. Unlike other companies, we chose not to do a basket study, and I want to, you know, maybe investors appreciate, maybe not, so I'll just review quickly. To set up a basket study means you get a group of the rheumatology, neurologists, et cetera, to partner with the oncologist around a single protocol, and then you go to the hospital and the administration of each of those departments, and you say, "I have one protocol. It's gonna be really easy. We get a lot of patients, and all you need to do is use our drug, and it's really easy to enroll in one clinical trial. It's easy to open up a site, because after all, we just have one clinical... You know, one legal set of documents, one budget. It, it all hangs together, and it is fast and easy." If your objective as a company is to generate the fastest and first clinical data in the industry, that's what you would do. But if your objective is, on the other hand, to launch the first product that is targeted and, targeted and curative for autoimmune diseases, you would do what we did. What we did was informed by discussions with FDA, both at the, operating team level in formal discussions, but also informed by more informal discussions, at more senior levels with the agency. What we came away with was the following: by having a separate IND for each indication, and within each indication, having separate cohorts for each subtype, we will have the most scientifically rigorous, homogeneous set of data, barring none. Using that as a foundation, we can then go back to the agency, we believe, based on early discussions, we can go back to the agency in order to discuss our early data in the first 6 patients of any one of our 10 cohorts, and ask whether, number one, a comparator is necessary, and number two, whether or not it is necessary, whether we can take what is a homogeneous clinical study set of data, set of patients, and simply expand the cohort that is already enrolling. If there's a comparator required, add in a comparator arm to that existing clinical study. That will save us the time it takes to open a new study. The reason nobody else did this is because it takes a very long time and an awful lot of effort to go through the same budgeting and contracting, and IRB, and cell therapy reviews for 4 or 5 or 6 INDs. It takes 4, 5, or 6, you know, times the effort for the hospital systems as well as for the company. And so it's very hard work to set the foundation that we've set. But going forward, we believe that if all else is equal on enrollment, we have the foundation built from which we can move directly into Phase III studies without starting new clinical trials, but rather by modifying the existing clinical study. In many of these indications and subtypes, there are no active therapies approved by FDA. In that context, we think adding more patients is the way to go. Where there is usual care that is deemed to be effective or where approved therapy exists, we would add on and propose adding on additional cohorts in our existing trials. All of this is gonna be driven by our data, not by the academic data. We're no longer, in a regulatory sense, at all, relying on the academic experience. That was a stepping stone for our company. We now today move into our clinical data, and we're really looking forward to the next six months, 12 months, and couple of years to talk about what the Phase III programs look like, to deliver that data, and to launch the first targeted curative cellular therapy in the industry. Does that answer your question? Yes, it does. And just really quickly, Steven, I mean, you know, as you say, you're gonna go back to the agency after you have dosed that six patients in any given cohort. I'm just curious, at how long after that patient is dosed? I mean, is it just completion of dosing, or are you gonna wait for three month data, six month data? I'm just curious if... Or is that still a little to be determined? Yeah, and it's a great question. So we are not gonna publicly say what our trigger is. Internally, we've obviously discussed at length. It'll be driven by the quality and quantity of our data, not only the data with the single cohort, but the broader cohort. Because I failed to say, you know, the activity, if you are providing a complete response in the vast majority of patients, proving that you are better than any comparator or better than no comparator, proving that you are effective, it's fairly easy. It's dozens of patients. And statistics would be on our side with those sorts of numbers, with any of these cohorts. But if you want to talk about safety in 100,000 potential patients or 1,000,000 potential patients, you want to have far more than that. The way we're addressing the safety question, part of which will inform when we go back to FDA to discuss our regulatory pathway to approval, is informed by how much safety data we have and the nature of that data. So because we have a single dose in every patient, with a single preconditioning regimen in every patient, confirmed by these first two patients, and, you know, I'll be the one to say, it's only two patients, but sometimes you have an engineering problem, and you recognize in cell therapy that's often the case... We feel pretty good about this on the backdrop of the 15 patients from the academic experience with a similar product. But at the end of the day, we need to see our own efficacy, our own safety, and our own data overall, to be able to inform the question, how soon we go back to FDA. And it's driven by the combination of how much follow-up do we think we need in that sixth patient, and how many patients do we have overall in the program, applying safety data from all of these cohorts to each of the indications? We believe that given the similarities in autoimmune disease across all of these diseases, the abnormality of the immune system being addressed in a similar identical way with an identical dose, that the combination of disease-specific safety data, plus compounded by, enhanced by the data from all of our patients, allow us to move forward with these regulatory discussions with FDA, pending again the quality and the quantity of the clinical data on all aspects, efficacy and safety. Does that answer the question? Okay. Yes, it does. Thank you very much. Thank you, Doug. Thank you. Our last question comes from Ben Burnett with Stifel. Your line is open. Hey, thank you very much. Congrats on these data. I just wanna ask just about the kind of the enrollment trends you're seeing or expecting in the clinical program. Just based on the epidemiology and the clinical trial footprint that you have, is there a certain type of myositis that we should expect to sort of dominate enrollment in that study? So those who don't learn from history are doomed to repeat it. We were arguably overly optimistic in 2023 about what we thought we could achieve in early 2024. So rather than guess and be judged on how well we guess, we will, you know, keep all 18 sites as the basis for going forward. We'll expand on all 18, with each of our four trials adding dozens, together, dozens and dozens, and dozens of additional sites across our program. And as we expand the number of sites, as we generate more clinical data, and as we begin to see how patients show up, we'll be better informed to start to address some of these important questions that you're asking. But at this point, it's too early for us or frankly, any other company to know, who's gonna show up and how quickly. You know, in a discussion with Professor Schett yesterday, he has been very impressed by two things that really stuck with me. One is the number of patients with scleroderma who showed up. He reported on 6 treated patients with scleroderma at this meeting. He was hardly trying, and the patients were reaching out through any way they could to get into the trial. I think that's generally, you know, similar to what we perceive, that like myositis, the unmet need in lupus, in scleroderma, is extremely high. These patients have terrible prognoses. In the case of lupus, if you're a 35-year-old... In the case of, I'm sorry, scleroderma, if you are diagnosed with scleroderma and you're 35 years old, and your kids are, you know, in tow in the doctor's office, and you're just diagnosed with scleroderma, you have a 50% chance that you're dead in 10 years, despite best therapy today. You know, think about that for a moment. Do you wanna try CAR T therapy if the safety profile looks like the academic experience and the efficacy is even remotely close? And the same in, you know, in myositis. Terrible situation for the patients to have almost no options. And in both of those, I have to say, there is almost no competition for sites or for patients right now. There aren't many pharmaceutical products and many cell therapies already IND cleared and ready to ramp up trials. So we are thinking pretty expansively, honestly, about our ability to continue to engage clinical study sites for those indications, as well as myasthenia gravis and lupus, where over 35 cellular therapies are actively being developed in the United States. I have to say, you know, of those 35 cellular therapies, on our last review, possibly about a week ago, all but two or three are talking about data from a single site or maybe from two sites, but no more than that. That's not a path to drug development and approval. That's a path to exploratory data. So our job is launch the first product in the field, having the sites is the first step, enrolling whoever shows up, and that is the objective, to enroll whoever shows up, who meets our criteria, and provide them the opportunity of the promise of a drug-free, long-term, durable, complete response. That's the objective in the program. So I thank you- Okay. for your question. I believe, I'll turn it over to the operator. Thank you. That will conclude the Q&A portion of today's call. You may now disconnect. Everyone, have a great day.