Fourth Annual Canaccord Genuity Growth Conference. I'm John Newman, one of the biotech analysts here at the firm. We are very excited to have Atara with us today. We have Pascal and, and Cokey with us today. Pascal, welcome. Thank you. I wondered if we could start with just a brief overview of Atara's core technology for those that may not be familiar, specifically your EBV allogeneic T cells, and how that is differentiated from other players in the space? Well, thank you, John, and thank you for inviting us to this conference. Atara is not only a leader in the field of cell therapy, in particular allogeneic cell therapy, but also a very differentiated and unique leader. We can say we are a leader because we are the only one having a product approved. The only approved cell therapy that is allogeneic today, T cell therapy, is EBVALLO, our product, also known as tab-cel, that has been approved in Europe at the end of 2022. We are now moving forward with the FDA for that approval also to come to the U.S. with a BLA that has been accepted, with priority review and a PDUFA date of January 15 next year. So an approved product, we are the only one, first allogeneic T-cell therapy ever approved in the world, and a process now for priority review and potential approval in the U.S. on January 15 for tab-cel. So that, being a leader, is being the first in that case, and we are the first. But we're also very differentiated because our platform of technology and allogeneic T-cells rely upon using donor-derived cells and making allogeneic EBV for Epstein-Barr virus T-cells. And this, in the case of EBVALLO tab-cel, allows to address some disease related to EBV, Epstein-Barr virus, which is this particular type of lymphoma called PTLD, for post-transplant lymphoproliferative disorder, that is post-transplant affecting some patient with a reactivation of the EBV infection, their B-cells, that leads to this lymphoma that is very deadly, very rapidly progressing. So that's how we can address some specific disease related to EBV. But the beauty of our platform is that we've been able to leverage that scale-up and that knowledge and regulatory approval of that platform now to produce allogeneic CAR T that rely on the same chassis of EBV T cells. So what we do, we take allogeneic EBV T cells, we know how to make them, and we insert the chimeric antigen receptors, creating an allogeneic EBV CAR T. Depending on the CAR we insert, we have different targets, such as, for example, CD19, for which we have developed an allogeneic EBV CD19 CAR T that is in the clinic right now. So that's very differentiated. Nobody else is doing that, and it's also differentiated in the fact that we have already a product approved, so we know how to scale up to commercial stage. We are treating commercial patients right now in Europe through our partner, Pierre Fabre Laboratories, and we've been through the regulatory process as well. So a true leader from that point of view, with a differentiated platform, which has unique, unique features in many aspects. The aim here is to create a true best-in-class in the field of allogeneic T cell therapy for lymphoma and autoimmune disease, which we believe ATA3219, our most advanced product that is entering the clinic right now, could be. Great. Thank you, Pascal. And just to follow on to your last comment, could we talk a bit more about your CD19 allogeneic program in large B-cell lymphoma, ATA3219? What I'm specifically interested in hearing more about is the unique features that are differentiated here, namely, the EBV allogeneic T cells and some of the other aspects here. Sure, I'll take that one. Thanks, John. So we start with the problem statement. What is approved in CD19 CAR T? That's autologous, and it's an alpha-beta T cell. So when we look at that problem statement, we look and say, "Well, that's what EBVALLO tab-cel is." It's an alpha-beta EBV-specific T cell. And it has this huge therapeutic index, and what I mean by that is a consistent response rate over 20 years, minimal graft versus host, and we don't see graft rejection. Because our solution is not gene editing, we use partial HLA matching. So we use the biology of transplantation. So right out of the gate, from the get-go, we maintain the T cell receptor with a very narrow, defined clonality against EBV antigens. Okay, that's the safety part. And then we have partial HLA matching to mitigate graft rejection. And then what we're doing is all the lessons Pascal alluded to that we've learned in how to make tab-cel to make a differentiated product. And so, let me describe those. The first thing is a next-generation chimeric antigen receptor. So that's one clinically validated element. It's called 1XX. This was last seen in Takeda's 940 program and autologous CD19 program. They showed amazing efficacy and a great safety profile that was superior to canonical approved CAR T programs. The second aspect is a memory phenotype that we tune in the manufacturing process. So much like Novartis' YTB program, it's a more memory-like phenotype, and also what we hope is with that, which also showed amazing efficacy and also a very nice safety profile, these two clinically validated elements on the EBV chassis are why this is a differentiated program, and that's why we're excited to get it into patients. Absolutely. Could you talk a bit about, a bit more, I should say, about the specificity, regarding the EBV T cell receptor and why that could be an important component of activity for 3219? Do you want me to start? Okay, let me start. Yeah, what we've seen again on tab-cel is that maintaining that viral specific T cell, in this case, EBV specific T cell receptor, is so important for, for one reason that Tessa Therapeutics have previously shown, but we've also shown in over 260 patients on our platform. That is, we use that T cell receptor, which is a survival signal that helps in manufacturing because we're pulling out these EBV T cells from healthy donors. But then when we look at the sequencing, they have a very clonal repertoire. And what that means is as these these T cells go into patients, what we've seen in tab-cel is very safe. So very potent, but also very safe because it's not. When you're making autologous T cells, you're stimulating polyclonal. Everything that is in your blood at the time gets stimulated, so any differentiation stage and even your autoreactive T cells. What we're doing is pulling out just that EBV specific memory repertoire, and it's proven to be quite safe. So we think that for manufacturing and also for patient safety, it's a super important aspect of our platform. I will add that on the efficacy side, coming back to what Cokey said, today, the only approved product, in terms of CAR T in the lymphoma and leukemia space, and of course, multiple myeloma, are autologous alpha beta CAR Ts. The only product having data in autoimmune disease, we'll talk about that later, are also autologous alpha beta CAR Ts. What we have in a very unique and differentiated platform is the closest possible allogeneic approach to what is an autologous is, because we maintain the property of the T cells in maintaining the endogenous native TCR, and we just add the CAR to it. So we have something that is as close as possible. So it's not only on safety with this amazing data set we have, having treated more than 600 patients with our platform already in different disease, but it's also on efficacy, the possibility to have something that can recapitulate or even improve on the efficacy results of autologous CAR T with something that is completely off the shelf, completely allogeneic, with very low cost of goods. Yeah. Okay, great. Could we talk a bit about the design of the ATA3219 study, including the number of patients and potential expectations for initial clinical data in terms of the timing? Sure, let me take that one. So it's an open label, phase I study, obviously looking at safety but also efficacy. There's four dose levels. We've been very public about this, starting at 40 million. Three to six patients per cohort, and then we have room for two expansion arms in the study. Obviously, it's in the relapsed refractory Non-Hodgkin lymphoma patient population. We expect initial data now Q1 next year, and we have lymphodepletion, so it's pretty standard. Okay. And what do you think investors should be focused on here in terms of the initial 3219 readout? We've seen a number of readouts for CAR T therapies in oncology. Your program is different just in terms of the way your CAR T is designed. What should investors be looking for, as we get into the first quarter of next year? Yeah, I think what is exciting for us is that first quarter next year, we should have this initial data. And initial data, of course, won't be a very long follow-up of the patient, but they will tell us a lot about the possibility of a platform to really deliver the promise in clinical stage in terms of the way our cells are expanding, persisting, are able to deplete the B-cells, to kill the B-cells that are in this patient, the cause of the disease, and then to be able also to have a good safety. And we have some very unique preclinical data that we like to see being recapitulated into this situation of clinical stage. 'Cause we presented data just a few months ago now that shows that preclinically, 3219 is able to have the same cytolytic potential, the same killing potential as an autologous CD19 CAR T benchmark, but with less inflammation, less release of pro-inflammatory cytokine. That's very exciting because that could lead to less toxicity in the clinic. That's to be proven, of course. But the ability for a product, due to its design, this construct that Cokey explained, to be able to kill as many B-cells as an autologous CAR T, but with less inflammation, that's going to be very exciting to see whether we can recapitulate that in the clinic, and that's coming in 2025. Okay, great. So moving on, we've seen a tremendous amount of investor focus, this year regarding CAR T in autoimmune disease, following publication of Dr. Georg Schett's academic study, in Germany, in Lupus, as well as some autologous CAR T data this year from, two separate biotech companies. Could you talk for a moment about how ATA3219 is differentiated here versus the, the other players in the space, which are, so many are autologous, some are allogeneic. Sure, let me start. I think we've talked about this because our product is based on tab-cel, and it's an EBV T cell. And our clinical experience is we don't use lymphodepletion. So right out of the gate, that's differentiated because not only is our CAR T program allogeneic, but it has the potential to go into patients without lymphodepletion. And when we talk to key opinion leaders, they think that's really important. We're moving into a new space where the patients do not tolerate lymphodepletion or these ICANS that are coming up, anecdotally in the clinic. And then obviously, what goes hand in hand with that ability, so obviously we're gonna do a study, one cohort with lymphodepletion in lupus nephritis, and then one other cohort in severe SLE without lymphodepletion. We think that we can do that because of our tab-cel experience. But also, if we go back to what we engineered, if you think about what we're doing with tab-cel, this is an effector T cell. We know how to manufacture. We've actually engineered more potency into the CAR program with 1XX and the memory phenotype. So it's all of these elements where we're reasonably confident that we can be differentiated. Not only do we have, out of the gate, a more potent T cell with less inflammatory cytokine release, but this ability to go in without lymphodepletion could be a game changer, I think, for us and also patients. Okay, great. And we saw some readouts this year from two biotech companies working with autologous CAR T in the autoimmune disease area. You know, I think that there were some questions after the data regarding things like CAR T expansion, B-cell depletion levels, B-cell rebound, reset. You know, we're still early here. There weren't a lot of patients. There's more to learn. But how do you think ATA3219 could address some of these questions? Do you want me to start? Let me start, and you can. Yeah. So I think, first of all, what's amazing about those studies out of EULAR, for example, and the biotech companies, is they're confirming the Schett hypothesis of the immune reset. I think it's sort of not surprising when you go into real-world situation, you start to see some relapses, and you might see some ICANS, because we're dealing with autologous CAR-T. So we've seen that in oncology, so we kind of expect to see that in autoimmunity. But we also think that there's room for opportunity to increase the potency and then also address the safety aspect. And that's why we're going also into that space, like others. We think the potency aspect, you know, the data, like to your point, are very early, so it's not clear if different disease indications require different levels of B-cell depletion. How does that relate to T cell persistence? Do you have the right dose? Because these studies are really going in at one dose, so it's sort of not methodical. Like you said, it's early days. And then the second piece of that. So that speaks to potency. And then the second piece, again, is, is safety, and I think Pascal alluded to this, but what you see with the Novartis program, YTB, and Takeda's 1XX program in auto, is they have a much better safety profile. What we mean by that is, in your typical autologous CD19 program, about 20% of the patients experience ICANS, which is the event that we saw the past week. With these programs that infuse fewer, more potent T cells, which we've incorporated into our product, I think the rate was 8% in the Novartis product. So that's why we think, again, there's room for improvement on the potency side and the safety side, but the data are still promising. Yeah, I think I will add to that also, that again, the fact that now some other teams, industry, biotech, and of course, pharma as well, are showing that their autologous CAR-T is indicating that they're able to have the same type of data as Dr. Schett, with some differences because they're treating more patients, more diverse populations, so efficacy could be optimized. Safety will have to be optimized, and that's why we believe our differentiation is going to be key in that respect of efficacy and safety. But also, these are autologous CAR-T. No data exist today, apart from three patients treated in China in an academic study with allogeneic CAR-Ts. And by the way, these allogeneic Chinese data are looking good. They say that the allogeneic product, which is a gene-edited one, is indeed leading to efficacy and safety. But one thing is important to keep in mind, that we don't see how autologous approach could ever be a commercial product in autoimmune disease. Just have that in mind. The first product were launched in lymphoma in 2017. YESCARTA was launched at the time, seven years ago. With seven years of investment, Kite Gilead have only been able, last year, to treat 6,000 patients. seven years of heavy investment in manufacturing, they treat only 6,000 patients. There is no way that an autologous, bespoke, one-patient, one-batch approach could treat the number of patients that are out there in need of a treatment in autoimmune disease. I mean, you have 170,000 patients in the U.S. with lupus nephritis. I mean, there is no way this patient could be treated with an autologous approach. I strongly believe, we strongly believe that autologous is doomed to failure in autoimmune, not only if there is something better in efficacy and safety, but this is not going to be a profitable business, a workable business, because they won't have the capacity to treat that many patients. Yeah. That's why allogeneic is the way forward, and we think we have a product that has been optimized to be best in class in that space. Sure. Could you discuss data generated to date for ATA 3219 in lupus? I believe you presented two posters at ISCT. Yeah Earlier this year. Yeah. Thanks, John. So it is a very well-thought-out experiment. So the question is, can our CAR T cells deplete or show cytolytic capability against B-cells from patients? Because you don't know for some reason why the patients are suddenly non-responsive to depleting antibodies. There might be some weird biology. So what we confirmed is that our CAR-Ts can deplete B-cells from MS patients, lupus patients. And the way that we did it was we tried to do it as well-controlled as possible. So we have a healthy donor, and then we make autologous CAR T, or we make EBV CAR T cells. And what was surprising to us was that the cytolytic capability was the same, potent and potent. But what we noticed in the EBV CAR T cells over multiple donors is we had a much lower cytokine burst upon activation, and I think that's consistent with our biology. It's 1XX, it's a central memory phenotype, it's the EBV platform. But I think what we're hoping is we see that benefit patients, because you are starting to see CRS and ICANS present in the clinic in response to autologous CAR T. So we were very excited to show that data, and that's, it's a key component for our safety. You spoke a little bit about this earlier, but could you talk a bit more about the planned phase I study design for ATA3219 in lupus? Sure. I'll speak to that. It's again an open label phase one study, and there's two components. There's with lymphodepletion. So what we're trying to do is mirror the study from the Schett group in Erlangen, which is to have pretty standard lymphodepletion. So it's a like for like. So you can really say, "Okay, you have these data, same patient population, and then we have these data with our product." That's lupus nephritis. And now, in a different cohort, which is severe lupus, but not lupus nephritis, we have this non-lymphodepletion protocol. And so we're gonna enroll both concurrently because they're not cannibalizing each other, and we're getting a lot of interest because we've come forth with this clinical trial amendment. And so, that's why we think, and Pascal can speak more to this, we think that we are gonna be reporting data from both cohorts at the same time, potentially, because there's a lot of interest now in what we're doing. Yeah, that's right. I think it's very competitive right now to do studies in autoimmune and lupus with cell therapy or bispecific, but we have a unique protocol in the sense that we have these two cohort in parallel. The fact not to have a cohort without lymphodepletion is very attractive for patient and physicians. We also opening site, not only in the U.S., but we plan to open in Canada and Australia, where there is a lot of interest and less competition. So we try really to get all possibility to get the enrollment on time, so we can have data mid-2025. In parallel, the data with lymphodepletion or without lymphodepletion, which I think will be very exciting to see and, could be game changing if we can show that we have the level of efficacy and safety that is linked with our differentiation and profile and technology, and then that we can use the product without lymphodepletion. Okay, great. And just a follow-on to your comments there. You know, patient enrollment has been a key metric in some of the Lupus studies for CAR T. Given that you're an allogeneic product and also that one of your studies is not utilizing lymphodepletion, how do you expect the enrollment could proceed for 3219? And curious if you will be focused on sort of larger academic centers for these studies, or if you'll also include some sort of smaller sites as well. Yeah, maybe I take that one in the sense that we have 4 key elements which make us confident that we can really enroll patient in this competitive field. One, of course, is differentiation of the product. We have a very, very different approach, and with the backbone of 600 patient treated with our chassis, with the EBV T cells, showing efficacy and safety. So that's very attractive for physicians to take our study on board because there is this reassurance that we have this type of data, clinical data from other type of product using the same backbone, the same chassis. The second one is this unique protocol that Cokey and his team put together, having this parallel cohort of lymphodepletion, no lymphodepletion. That is also something very attractive because in lupus, in particular, you have relatively young patient, a lot of women of childbearing age. None of these patients want to take chemo. You know, with the toxicity of chemo, the impact on everything, on their health and their future, they don't want to take chemo. So here we have a proposal without chemo, which I think could makes a lot of sense for them. So that's very attractive. The third point is that we are using a CRO that is very expert and has done a lot of study in that space, and they know that very well. And the fourth one is what I mentioned earlier, is to open site in Canada and Australia, because this is where there is less competition from a study point of view, and we think that we have experience with what we did in MS in the past in Canada, so, and in Australia as well. So we know how to handle this type of site. So this explain why we think that we will get the enrollment that we need to get to have some data in mid-2025, initial data in mid-2025 there. Now, at this stage, I cannot comment on what type of centers. We're discussing with a lot of different centers there. You still need to have a connection between rheumatologist, hemonc, and cell lab. So you need, at this stage, a situation where you have enough resources within the site. Now, we had experience because we had another product called ATA188, where we have treated 150 patient with progressive MS in the past, and we know how to go to community centers. That product was not requiring lymphodepletion, having just the two hours monitoring. It was used in 150 progressive MS patients in outpatient clinics with neurologists that were not used to cell therapy. So we have that ability, if the product is confirming safety, to go into that type of centers, at the proper time. Okay, great. We have just a couple of seconds remaining here, but just curious if you could, one question here on tab-cel. Could you, remind us of the commercial arrangement there in the U.S.? And I think you'll be, there's an opportunity for some substantial cash inflows on that product, if you could remind me. That's right. So we have now a global agreement with Pierre Fabre Laboratories for commercialization of tab-cel. They are the company already commercializing in Europe. Now they are getting organized to commercialize the product in the U.S. They have already recruited their team there, and they are getting ready for PDUFA date that is January 15. So they will be ready to launch, and at the time of the approval, we will get $60 million milestone for approval, plus we will transfer all activities to Pierre Fabre, so we can reduce our cash burn on tab-cel and just focus on CAR T. Plus, we'll also sell to them some inventory of intermediate and product that we have that will bring some additional cash to the company. So it's a very important event from the point of view of starting the commercialization of this product that has no competitors. There is no product approved in that space. It's ultra-rare with a high price potential, so Pierre Fabre is going to make the most. We have then, significant double-digit royalties for them and sales milestone. So the first step in terms of cash will be the approval, the milestone, the reduction of cash burn, and the, sale or purchase of inventory by Pierre Fabre. And then the second step will be for the launch, significant double-digit sales royalties and sales milestone. Excellent. Great. Well, Pascal and Cokey, thanks for joining us today. Thank you to the Atara team, and thank you to all the investors here in the room in Boston and on the webcast. Thank you very much. Thank you. Thank you.