Cabaletta Bio, Inc. (CABA) Earnings Call Transcript & Summary

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 is a President of Science and Tech at Cabaletta. Pascal Touchon, CEO and President of Atara Bio and Kevin Xie, CEO and President of Gracell -- CFO.

CFO. CFO.

CFO, I'm sorry, CFO. 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 1 to 2 summary of your company and what you're working on?

Yes, 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 2 INDs open. The first is in lupus with 2 cohorts, 1 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 3 cohorts there, 1 in antisynthetase myositis, the other in dermatomyositis and then immune-mediated necrotizing myositis. We have given public guidance that we intend 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 3 programs 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 allogenic T cell therapy that is targeting some specific cancer related to Epstein-Barr virus initiation. And we have allogenic 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, approved, now launched in Europe and is 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 allogenic 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 2 months' time, we'll have a readout of that study in progressive MS patients, which is aiming at improving disability in MS patients. And 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., latent infection with EBV. And 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. And they all benefit from the same platform around allogeneic EBV T cells coming from healthy donors that we're able to manufacture at scale because we are a 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 3 technology platforms. One is a FasTCAR, which is the next day manufacturer -- autologous manufacturer platform. Two is we call TruUCAR, it's allogeneic technology. Third, SMART CART, our solid tumor program. We have 5 programs in the clinical stage, collectively have treated 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 TruUCAR on the [heme] and then SMART CART 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 starting to enroll patients in China through an investigator-initiated trial.

Great. Thank you for that. So I think there's a growing body of interest from both investors as well as corporates like yourself in 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 your programs? I know that it seems like you all have a CD19. So I think that would be great to hear from you.

Yes, sure. Thanks for that question. So recently, there have been 10 published reports from the investigator at FAU University, Georg Schett, using a -- 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 9 days. And this has led in 10 patients, so it's 7 lupus patients, 2 myositis patients, 1 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 remission of therapy and in the systemic sclerosis patient that patient's disease has completely been -- progression has 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. So our construct is functionally identical to this construct that was used in the Schett's study, which has very clear clinical proof of concept with the 1 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 later -- come on to later in the discussion. But in short, it has allowed us to open 2 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, 5 shots on goal, 5 indications, which we will be rolling in parallel without a requirement for dose escalation. So that means a 6-patient pilot study. In any 1 of those first 5 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 2 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 cells, the allogeneic cells. And 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 lymphodepletion for 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 lymphodepletion. And 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 2 years without any issue in terms of the relapsing. At the same time, we have optimized our costimulatory domain with 1XX, 1 invented by Michel Sadelain in MSKCC that is leading to less T cell exhaustion, hence enabling more functional persistence of the T cells. And then last but not least, we are manufacturing the product in a way that maintain memory T cell phenotype. So having the EBV T cells, 1XX with costimulatory domain and memory cell phenotype enable us to have optimized all the way toward more persistent allogeneic sales coming from healthy donors. But 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 a first-ever study with an autologous type of T cells for MS treated 10 patients in a Phase I and 7 out of 10 had positive response in terms of improvement. You have to consider that we're talking here about progressive MS, the disease where by definition, these patients are progressing in disability. They are declining with time. And here, you had 7 out of 10 that improve on disability. Now we replicated that with an allogeneic program ATA188. In Phase I, we have treated 24 patients. And over the 1-year study, plus an open-label extension, all the patients that we followed, we have only 4 out of 24 that progressed. I mean, 20 out of 24 either were stable or improved. In fact, 7 out of the 24 improved, 13 stable, 4 progressed. That's unheard of in progressive MS because the patient should be progressing with time and here with patients improving and, in fact, or being stable. And that's what we're doing in our Phase II study now, and that's what it influenced that also last year, there were 2 amazing papers, 1 in science from Harvard team that shows very clearly that multiple sclerosis in 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 trigger. We believe it's also the driver of the disease. And we believe so also because there was another paper in [Natural] 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 patients 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 the brain, is in fact is 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 progressive MS with this allogeneic T cell therapy targeting EBV with very acceptable 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.

Yes, seems to be a theme. Kevin?

Yes, sure. The paper on nature late last year, obviously was very groundbreaking and there's great news to the patients that autoimmune disease is a large market and lupus, for example, has huge unmet needs. The current standard of care does have very marginal clinical benefit. So compared to what the paper have shown. And so obviously, companies large and small, with similar program are going into this field or thinking about going to this field. So the question is that whether CD19 is enough and how durability will look like, how the safety profile look like. So those are the questions that I'm sure that the markets are waiting to see. So for us, our leading program 12F with CD19 BCMA. So far, we treated about 60 oncology patients and mostly on multiple myeloma and also some lymphoma patients. So we have had a lot of experience. But first, we can look at that what does the BCMA can offer besides CD19. So there actually has been studies, including [indiscernible], have had paper in 2016 that is suggesting there is a group of plasma cell antibody secreting cells that can stay in the plasma for a very, very long time, maybe lifetime. That over time can still trigger the immune system reaction. And the BCMA obviously express on the plasma cell. And internally, we also have a 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 the addition of BCMA's dual target is going to potentially add clinical benefit to 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 late-line oncology patients, right? So for us, fortunately, we already have about 60 oncology patient data with very, very let's say a tolerable safety profile. What does it mean? It means we haven't seen any ICANS or [neurotoxicity] of any grade. We mostly seen very low-grade CRS, Grade 1, Grade 2. And for example, one of the cohort, we have a frontline newly diagnosed multiple myeloma study had 16 patients, 75% of that patients actually had 0 CRS event. So those data give us a lot of comfort to expand this program into the 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 manufacture process is overnight process versus typically it is days or weeks process. Obviously, that means FasTCAR get back to the patients and it offers multiple benefits, both therapeutically and economically to the patient and the health care 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 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 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 autoimmune cell therapies as opposed to where everyone's got a lot more experience in oncology.

Maybe I can start with 2 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 5 to 10 minutes IV of the cells and then 1-2 hours monitoring that's it. So the patient can be treated in outpatient clinic. That's also possible because of the safety. As you said, Yigal, 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. I said more than 120 patients treated already. And again, we have repeated treatment because in all possible administrations, we are testing cycles of administration that are repeated once a year. We have some patients that have been treated more than 4 years now in our Phase I 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 4 years later. The patients that were improved are still improved 4 years later, except 1 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 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 ATA188 and they are fine with it because it's very easy to use. It's no different from a monoclonal antibody. In fact, it's easier if you use ocrelizumab, OCREVUS in MS, it's a 4 to 5 hours IV with a lot of surveillance as well of the patients. Here is just 5 to 10 minutes, [bolus of cell], that's it. So that neurologists were not used to use cell therapy in an autoimmune disease -- neuroautoimmune disease to get comfortable with that. And now they are fine. They don't see any issue with the use of cell therapy. So safety to be able to make sure that you monitor that ideally try to limit [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 a monoclonal antibody. It shouldn't be any major difference there. Of course, you have difference in the logistics, allogenic is pretty easy. You ship that within 3 days, is delivered to the patients. but still they need to have somewhere where the cells are being cryopreserved. But then you just [thaw] 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 only for depletion is key for autoimmune disease.

Yes. I would agree with most of those points. I think definitely, the bar for safety is far higher. And the ability to grow 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 current preconditioning that 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 of 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 1 infusion and leading to long-term durable results. Safety, safety, safety, for us selecting a binder that is fully human has been also shown not to have neurotoxicity, CRS ,the 4-1BB costimulatory domain also shown across multiple in vitro studies. And also if you look at YESCARTA or KYMRIAH out of the market, YESCARTA usually needs in-patient 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 and anything -- you can go for anything? Or are there some limitations?

Yes. The field has really expanded and 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 the 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 auto antibody 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 -- 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. Because of -- 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 data, now it's really opened up 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 us are extremely diverse, heterogenous. So how the patient will react from an efficacy and 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. There is possibility to also attack plasma cells because you have some of these long-term plasma cells that are producing antibodies. And we have that example with a product, which explains why we believe that we have a better efficacy on CD20. Because CD20 will not eliminate plasma cells, we can eliminate plasma myself. 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 can't cross well the blood-brain barrier. That's why ocrelizumab and others 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. 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 that 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 German -- presented about here 4 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 going to be to bring these drugs to the market in the U.S., given we have this very unusual setup. Second question is on preconditioning, which is acceptable within oncology setting. But in a refractory autoimmune setting, if you don't need it, maybe you don't, I'm curious what 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 is kind of a discrete opportunity. But you also referenced eliminating plasma cells. So BCMA, CD20, CD22. So yes, we've stumbled across CD19, but is that the right opportunity. And then the final thing, that is 4, and I'll remind you if you lose track, but the fourth one is supply chain. So you have 2 guys with very big guns and lots of capacity who are blazing the route here. And while you may have interesting sale constructs, it's going to be a race. So how do you participate in that? Presumably you need a partner manufacturing supply. You hope to hook up with J&J, Lilly, Astro and Roche, what's the appetite? I know from my conversations, many of them are holding out for allogeneic cells rather than diving in for [autologist], so I'm just curious. So here we go. There we go. I warned you, there's going to be a shopping list. You can take whatever those resonates the most.

Yes. So these are questions we been receiving over the last couple of days. And so 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 it. 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 6 patient pilot cohorts without the requirement for dose escalation, because we were able to draw from the compelling data from Germany and basically say, look, our -- 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. So that's the rapid clinical trial development approach. And if -- while we're not commenting on clinical -- later-phase clinical trial designs, you can draw from oncology. If you look at, for example, what Kite did, in their YESCARTA development pathway, they converted an early Phase II late phase clinical study.

Okay. And maybe on that, I mean, we have an interesting level of interaction on the CD19 allogeneic CAR T is more on safety. Because of the allogenic part of it and so on. And that's understandable, but we were able to clear the IND for lymphoma and therefore, we can move forward. But with ATA188 where we 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. And we're also running now a placebo-controlled study, which is, to my knowledge, the first ever placebo controlled study in cell therapy and autoimmune disease, and that's going to read out in November. And the [ATA] was very, very nice to us to support us, and they gave us 2 fast track designation for ATA188, 1 in PPMS, 1 in SPMS for that reason but they're already thinking with us about the Phase III and how they go to Phase III with that type of program. So I would say the ball has started to roll with the [indiscernible] in terms of thinking about pivotal development in autoimmune disease of cell therapy. A bit on allogenic and maybe on your last questions, I mean, allogeneic, we believe, is a key there because we already scale up. We know that we can make thousands of doses with 1 leukopak. In fact, [indiscernible] and we have the data to show that once we have a pivotal commercial stage is to make up to 20,000 doses from 1 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, logistics or supply and we've treated with all the product plus ATA188 in both cancer and terminal disease, more than 500 patients worldwide. We delivered that within 3 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 [autologist]. 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 an [autologist] approach, why you are hesitant about the allogeneic alternative, which your colleagues are exploring?

Sure. Yes. 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 first launch with 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 thinking about what other modalities or how can we increase scale with our current modality, and those are very 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 5 years of our operations. We have plans to build our own facility, and we are also, of course, looking at 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'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 eyes 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...

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 pooling into this field, and we have experience on both. So at the end of the day, is the end result of the patients, it's efficacy and safety. So in our experience, for example, the percentage of [CRs] from allogeneic program versus autologous, there's still a gap. The safety in terms of CRS that we have consistently seen much better safety profile from autologous for the reasons. I think there's a much 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 gives 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 a 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 with 2 round of Cy/Flu. Why we're doing that because we already have 60-patient oncology -- 60 oncology patients data that's generating very consistent, tolerable safety profile. So that's a good starting point for us there. We're starting with the same dose, which is 1x10^5 per kilo. So it's about 1 million cells. And this is a good starting point for now. And certainly, we wanted to have ideally not having even less lymphodepletion cycle or even without 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, Lonza is supporting us in the U.S. for Phase 1. And the fast manufacturing process we have, which is the 2-day process in terms of the time taking the [indiscernible] 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, is going to yield significant economic benefit for both the company and also to the health care system.

Great. I think in our final minutes, maybe we can squeeze in 1 company-specific question for each of you. So perhaps I can start with you, Gwen. So you're going to have your initial data in the first half of '24 and it can come from any of the 5 cohorts that you've spoken of and potentially more than 1 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?

Got you. Got you. Thanks. So in terms of -- so we've given public guidance that we will announce initial 3-month data from our -- from -- 3-month data from patients in the first half of 2024. That data, if you look 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 3 years. We've treated over 16 patients in a dose escalation study. And that has been published over time. You can look at some of the corellative type data. We also -- we 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. 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 ahead of the curve with now about 2.5 years of follow-up and still in clinical remission. And 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. And 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 for certain steps of the process and so forth. And those are things we're well ahead of the curve on and we'd 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 in the interim until we get to Stage 3 of our manufacturing strategy, which is our own facility and potentially a strategic partnership.

Pascal, you mentioned the EMBOLD data in November for ATA188 in 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.

Yes. 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 [transformational] pivotal study type of criteria is confirmed disability improvement at 12 months. Confirm means 2 consecutive time points. So it has to be at least 9 months and 12 months, patients are evaluated every 3 months. And it is disability improvement measured by EDSS, which is the validated scale used for any type of regulatory approval in that particular space. These are progressive MS patients, but 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 lesion. But 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 including the nonactive part. So it's very limited armamentarium 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. So we'll have data on that 12 months confirmed disability improvement. We will 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 improves with time, 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 armamentarium or battery of biomarkers, both imaging biomarkers, MTR, MRI as well as a number of feed biomarkers available, that will be disclosed in terms of that 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'll 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 maybe beyond progressiveness. But that's a very exciting catalyst for us. And before that, we will have important catalysts also coming on top sell 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 of the FDA to be able to give some new guidance on the timing of the BLA that we expect to be relatively soon. And at the same time, we are actively negotiating with potential partners for a U.S. commercial deal. So ideally, we would like to see clarity of the FDA, the 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 2 months. So most exciting 2 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 the next, in 1.5 '24. 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 will answer your last question first, no, we're not waiting for the [IIT] 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 [IIT] obviously is going to give us additional insight on the real 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 we would like to see is some patients have had 9 months even -- some patients -- definitely half of the patients will have, I would say, 6 months follow-up time and some of them may even have 9-month follow-up time. Some is relatively early, maybe just had a 3-month follow-up time. So the key metrics we're going to report is the same as with all the other trials in terms of safety and efficacy on the [SLEDAI] score system. And 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 was a [SLEDAI] score starting from and all that. So I think there will be a lot more information for the market to digest in the next 6 to 12 months.

Definitely. It sounds like a lot of really great data in the next 6 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.