on oncology and autoimmune disease. We benefit from a platform that is extremely differentiated, very unique, in the sense that we rely on donor-derived, allogeneic EBV, or Epstein-Barr Virus T cells, that we extract from donors, and we're able to manufacture it, and this is the backbone of our different products. And what is amazing is that we are the only, so far, and first and only approved therapy, as an immunotherapy based on T cells Ebvallo that has been approved in Europe and is going to be hopefully approved in the U.S. relatively soon. And that's the backbone of our platform, on which then we are building a very exciting product called ATA3219, that is targeting CD19 as an allogeneic CD19 CAR-T.
But a very, very different allogeneic CD19 CAR-T compared with anything that exists, because we are the closest possible to an autologous CAR-T, but being off the shelf, being allogeneic. Let me explain why, and, and Cokey will, will detail that later on. It's really around the idea of having something that is benefiting from our platform experience. We've treated more than 600 patients with our different products so far, with great safety over several infusion and several years of follow-up. At the same time, we've optimized all the elements, all the features for an allogeneic CAR-T that could be potentially best in class. So that product, ATA3219, is now in a clinic in lymphoma, and we also cleared recently an IND for lupus nephritis, and we are moving into that study initiation for the second part of this year.
We have not only a cohort looking at lupus nephritis, where we use lymphodepletion in the same ways as academic studies have been published so far, but we have also a very exciting cohort we plan to initiate without lymphodepletion. And we'll give you more details later on, but we think it's very important for the patients, especially autoimmune patients, that do not want to receive chemo, to test how we could use a product or allogeneic CD19 CAR-T without lymphodepletion. And the reason we think it's possible, and we'll detail, is really because we have experience already with that cell. So that's our first product, ATA3219.
We expect to have initial clinical data on the lymphoma study at the end of this year, in Q4, as well as initial clinical data in the lupus study for the cohort in lupus nephritis in first half of 2025, for the cohort without lymphodepletion in SLE in the second half of 2025. Now, we also have a product called ATA3431, that is at preclinical stage right now, which is dual CAR-T targeting CD19 and CD20, with great data preclinical stage, that shows that we are better, more potent, more effective than autologous benchmark. And this product is planned to go through an IND in the second half of 2025. So that's for the CAR-T exciting portfolio that we have, which is again, very differentiated.
Now, we have also tab-cel that is approved in Europe, and we filed the BLA for the U.S., the U.S. FDA in May of this year, so we expect to get the BLA acceptance hopefully relatively soon. And then if the product gets a priority review, it has already a BTD status, so hopefully we could get priority review, it could be approved in the first quarter of 2025. So very exciting next, 12-18 months for the company.
Great, let's start with your allogeneic CD19 programs. You know, there are clearly many players in this space, so help us understand, A, how you think about differentiation, but B, maybe discuss some of the challenges that we're seeing in the field right now.
Cokey, you want-
Sure, let me start. Thanks for the question. I think the problem statement is what we call the allo conundrum, which is: How do you get donor-derived or foreign cells into a patient and avoid alloreactivity, which is attacking the patient, or a graft rejection, which is rejection of the drug? We think, based on our EBV-specific T cell platform, it's an elegant solution to this using natural biology. And what we're trying to achieve is you take all the efficacy you've seen with the autologous approved products, Kymriah, Tecartus, Yescarta, but with off the shelf. And that's what we've designed, and that's what ATA3219 is. It's really, beyond the problem statement, three points of differentiation, right? There's the biology is number one, that we're again, accessing this very potent population of T cells from healthy donors. It...
We are maintaining the T cell receptor, which itself is a survival signal. We don't think it's a great idea to edit that out. We don't do gene editing, and we think, favoring our biology approach versus gene editing really favors the biology of T cells. Gene editing, could wreak havoc on the fitness of those T cells, its CMC complexity, and there's also potentially regulatory challenges the more editing you do. The second piece is really, we've seen with tab-cel, over 20 years of the tab-cel experiences, we know how to make this product. It has an amazing therapeutic index, which again, is efficacy over minimal, safety events. We've seen from our EBV T cell programs, over 600 patients, again, no issues, but very, potent.
And the last piece on the, on, on top of this chassis is really: What did we learn throughout time? We've engineered two main elements. One is this next-gen chimeric antigen receptor, which is called 1XX. It's differentiated because it's CD28 based also, versus the 4-1BBs. We know from the Takeda data, amazing potency and efficacy with their autologous program. And then the last piece is, we've learned so much from how we make the T cells. We can optimize manufacturing for a memory-like phenotype, and this has been shown best exemplified by Novartis's program, really enhanced potency and persistence.
You plan to report first phase 1 data in non-Hodgkin lymphoma in the fourth quarter. Could you frame what you'll present, how to think about the relevant benchmarks here, and how this release will inform your next steps?
... Oh, I thought you were going to take it, but, so I, I can take it. I think what's happening is that we will have a few patients available of data at the time, but we think that these first few patients are going to be very important. In fact, when we discuss with many experts and many potential partners as well, they all say the same thing, that the first few patients, if we can show the type of efficacy and safety that we expect, together with some PK data that shows that you have the right level of expansion and persistence of these allogeneic CAR T, we have then a confirmation that our platform is really delivering what we've seen at the preclinical level, and also what we've seen from all the clinical data coming from each feature of the product taken separately.
You know, it's very amazing that you have a product that is now starting its clinical program, but with five elements that each of them have been proven clinically to be not only safe and effective, but to be potentially better than the existing. The platform, which is this backbone of allogeneic EBV T cells, this costimulatory domain 1XX that has been shown in a clinic in autologous program to lead to a better potency and very good safety compared with other autologous program, where you can use 10 times less cells, 25 million in a Takeda program, compared with the 250 million of cells. So you use much less cells because you are more potent, but at the same time, you don't compromise safety. The third element is the memory phenotype, because clearly having that memory phenotype allows to have also a lower dose.
I mean, Novartis' example is interesting, where they use only 12.5 million cells per patient for an autologous CD19 CAR T. We don't know yet what those will be. We start at 40 million, but we know that our cells will be more potent because they have more memory phenotype from that point of view. Then the fourth element is really around the experience that we've had with our backbone, where from a safety point of view, we've seen that the product has been able to expand, and that's the case with that cell, even without lymphodepletion, and be very safe. And then the fifth element, which is very important, is that we are doing partial HLA matching.
There was another company recently showing data in their gene editing allogeneic CAR T that shows that when you do partial HLA matching, you have better response and you have longer response. And that's really what we aim at. So you see, these five elements are all in one product, which is ATA3219, and that's why we're so confident that these first two patients data will be of extreme importance for clarifying the value of the platform, that data is building and developing, and therefore the differentiation that we can bring to the field of CD19 CAR T with an off-the-shelf allogeneic that is better than the existing and the product in development.
Ignoring the target here, you've done prior work with your platform and, and CAR Ts. Help us understand what you learned from that, and also, how you think you could then fit into the treatment paradigm here. For instance, with CD19 and lymphoma, could you be used post-autologous therapies, which has been, in some cases, difficult for the other allogeneic approaches?
Yeah, I mean, what we're doing in our lymphoma study is to look at two type of patients with lymphoma, with non-Hodgkin lymphoma. One type of patients are post-CAR-T or post-CD19, bispecific and CAR-T type of CD19 positive, of course. And then naive patient as well. It's for the patients, again, because of the different product and the ability to have potentially better persistence, functional persistence of the cells that we've shown in preclinical model. In fact, in preclinical model, with ATA3219, we've shown that we are better than the benchmark autologous CD19 CAR-T, which is a top-selling product right now from another company. So we have shown that better effectiveness in preclinical model that we think could really translate into clinic very soon.
You also spoke about your effort in autoimmune disorders. When may we see this first data set, and what is your dosing strategy? And within that, how are you thinking about B-cell depletion or the, you know, the level that you'd like to see in the phase I NHL data that will give you confidence in the expansion to autoimmune?
Yeah. So as Pascal said, we have a safe to proceed with our IND and auto, and we're looking at lupus nephritis first. What is unique about this space is you've only really seen proof of concept with an autologous CAR T product. And why that's important to point out is, again, we haven't seen any allogeneic data yet. And so what that tells us scientifically is you want to mimic as closely as possible autologous alpha-beta T cells. So that's why we're also moving into the space. We think that it's also important in this space to think about this immune reset that people talk about, and it's not clear that you will get that with biologics, and there's also the question about chronic dosing versus one-time dosing.
And, we can expand from there, from lupus, and we obviously can look at other opportunities in the B-cell space. To your point about B-cell depletion, we think the data say that you have to be pretty exhaustive. And in other words, it's likely a lot of these patients will see something like Ocrevus, which is a B-cell depleter, but for some reason, that hasn't shown clinical benefit per se. And that's why we think it's been so amazing to see the data of the CAR-Ts. You must have some level of deep B-cell depletion that only a T-cell-mediated therapy can accomplish.
... What are your thoughts on the potential to reduce or eliminate lymphodepletion? Maybe talk about your features of your approach here and how you might be able to ensure that.
Yeah, that's another great topic we're talking about. And we get from them is, this is very different from oncology. Autoimmune space, you're asking for a set of heme oncology docs to do lymphodepletion, and then a rheumatology staff to follow disease progression or disease improvement. We think to unlock the potential in autoimmune, you're gonna have to think about two things: number one, the outpatient setting, which is not lymphodepletion, and the second is minimal disruption to the patient and what they're currently on. That's why no lymphodepletion is gonna be important in this space. We're adding an amendment to our IND to not use lymphodepletion to treat cohort, which is severe SLE.
The why we are thinking about going into this space is really based on our clinical experience, so the scientific rationale is obviously based on data. What we've seen with tab-cel is three things, right? Safety, consistent potency, and the last piece is obviously all the other elements we've engineered on top of that. So the safety piece we've seen again in 600+ patients. We haven't seen alloreactivity or graft versus host issues or host versus graft. The second piece is, without lymphodepletion, we've seen efficacy with tab-cel. We've seen PK/PD parameters, correlates with efficacy, so that gives us confidence that we have the right platform to go without lymphodepletion. And then you can imagine, based on that chassis, then, you thoughtfully engineer again this better co-stim domain in the CAR and this memory T cell phenotype.
This is why we're very confident about trying this in the clinic.
Could you provide an update on your allogeneic CD19, CD20 CAR and the strategy for this asset?
Yeah, given also that maybe one thing I would like to add on the safety aspect of our platform is not only that we have treated more than 600 patients now, but about 130 of these patients were with progressive multiple sclerosis, and that was with another product called ATA188, that was developed to be able to eliminate the B cells infected with Epstein-Barr virus in the brain of this patient as a potential cause for the disease and disease progression. But what is very interesting from this data that we have is the safety was very favorable, and these were fully immunocompetent patients. So they've been treated, 130 of these patients, for several infusions, several years of follow-up, without any safety issue, be it GVHD or ICANS or whatever type of neurotoxicity or, of course, CRS. Nothing.
Nothing at all. And that's very exciting because that means that our backbone technology and platform is really able to be used in autoimmune patients with great safety, even with repeated infusion and several years of follow-up. And now we have also a very exciting data coming from an abstract. We presented a poster at the recent International Society of Cell and Gene Therapy Congress, where we've been able to show that preclinically, ATA3219 is able to fully deplete B cells, which is expected to have a very high level of cytolysis to kill all the B cells there in preclinical model at the same level as an autologous benchmark, but with much less pro-inflammatory cytokines release.
That's very exciting because that's how we built it as a possibility to have a very good killing power on B cells, but limiting the pro-inflammatory cytokines, which are the potential for toxicity in these patients. So having a product that preclinically is safer than autologous CAR-T CD19 CAR-T, and clinically is leveraging the backbone of allogeneic EBV T-cell have been used in many patients, including more than 100 of autoimmune patients with good safety, is something that shows that we have a very unique type of product to go to autoimmune disease. So coming back to CD19, CD20 now.
Yeah. So we have a program called ATA3431. It's dual targeting CD19 and CD20. Why we're excited about the program is targeting both antigens is probably essential in oncology, where you often see antigen escape. We do see this with CD19-directed therapies. We've seen amazing data from the autologous programs, a couple now, where the overall response rate is 90%, the complete response rate is 70%, and that's differentiated from CD19-directed autologous, where the overall response and complete response rates are a little bit lower. So it seems like you're gaining potency by targeting two antigens just in oncology. In autoimmunity, I think there's another opportunity that we're excited about, and that's because twenty, again, is validated in autoimmune disorders. Ocrevus does work in certain autoimmune disorders.
So again, we're looking at the data as it emerges from autologous approaches cautiously. We think it's gonna emerge in the next months, but we think with this program, we have this ability, again, off the shelf to take that efficacy you see with autologous programs, again, present patients and physicians with an off-the-shelf solution and then move into oncology and autoimmunity.
Right. Let's turn to Ebvallo here. Could you provide us an update on how the EU launch is progressing and the upcoming milestones in the U.S.?
So in Europe, it's our commercial partner, Pierre Fabre Laboratories, who is commercializing Ebvallo since they got the transfer or the approval in March 2023. So it's a bit more than a year now, and the launch is on track. I mean, they're very pleased with the launch. Maybe three elements why they're pleased. First of all, from pricing point of view, they were able to get a listed price of EUR 75,000 a dose, and on the pivotal study, it was about 7.8 doses per patient. So that means is a price per patient of about EUR 585,000, which is about $640,000 at the current exchange rate. So that's significant pricing.
They have a few hundred patients every year with second-line PTLD in Europe, and now they are working on, of course, stimulating the demand. Interestingly, in Q1, there was about two-thirds of the twelve-month demand were in Q1. So it's really accelerating from that. When you see overalling type of demands data, I think two-thirds of the demand in the last quarter is showing that the launch is progressing well. The third aspect, of course, reimbursement, pricing and reimbursement. So they are very hopeful that by the end of 2024, they should get the top countries with pricing and reimbursement, and that will be really in 2025, where we'll see then the acceleration of the sales. So very, very good start in Europe.
In the U.S., we filed the BLA in May, and so we are now waiting for the BLA acceptance. Hopefully, you know, typical 60 days period there and clarification of PDUFA. If again, as we have a BTD status, if we get a priority review, which is possible, that will mean probably Q1 2025 for a potential approval of the product, if everything works well. And Pierre Fabre is getting ready to launch the product in the U.S. As you know, we've done an expanded agreement with them for them to get the global rights now, and they have started to recruit their team. They plan to recruit about 70 people in the U.S. They have already a CEO with the former G.M. U.S. of Kite, so she knows very well the activity of cell therapy in hem/onc, as well as with transplanters.
She has recruited a very stellar team of expert and leaders covering all the different functions to be able to launch that. And what is very exciting for us is that Pierre Fabre Laboratories was not present yet in oncology in the U.S., but they have recruited this great team, and they're going to be 100% focused on that cell. And that's why it's very exciting to see how they're going to be able to be ready to launch the product, hopefully in Q1 2025.
Just remind us here on the milestones, the near-term milestones.
Yeah. So that expanded deal on top of the open deal was to bring up to $640 million of value, upfront and milestone, and significant double-digit royalties for us. So right now, we've already received about $27 million at signing. It was $20 million, upfront, plus $7 million of inventory so sale. We received another $20 million for, following a positive pre-BLA meeting that we had with the FDA. That was received in April. We have another $20 million coming, hopefully at the time of the BLA acceptance, so relatively soon. Then we have $60 million at the time of the approval. That's for the regulatory milestone. Then beyond that, once the product is launched, we have these significant double-digit royalties on the sales, plus sales milestone. So it's very good and, exciting, situation for us, for Atara.
What are next steps as it relates to the expansion opportunities post the phase II multi-cohort data that we saw at ESMO IO?
Yeah, there, there were some very exciting data we presented. In fact, we are running that study called EB Vision, across different type of cohorts that could lead to label expansion once the products are approved in the U.S. and certainly in Europe, once the data are mature enough. And so over the next few years, we hope to be able to discuss with regulatory authorities based on the data and, trying to get some label expansion. Now, at ESMO IO in December, we presented very exciting data on 18 patients with, PTLD, with CNS expression, and some of them, in fact, were a first-line patient. One was first-line patient.
That's very important because CNS PTLD is about 15% of the case of PTLD, but the typical treatment that is being used for this type of lymphoma is anti-CD20, like rituximab, and this doesn't cross the blood-brain barrier very well, very efficiently. So the prognosis of this patient with CNS expression of their lymphoma is very poor. Now, we get this data on 18 patients, showing that we have-
Excuse me.
Bless you. We have about 77+% response, so very high level of response rate. And what is striking is that the overall survival at one year on all patients treated was over 70%, but it was nearly 86% in responders and 0% in non-responders. Again, showing how severe is this type of post-transplant lymphoproliferative disorder, particularly with CNS expression, because all patients that are not responders or that will not have been treated will die within a year, and we are able to save 86% of them for one year to be in 86% of all survival at one year.
So very dramatic impact of tab-cel in that type of situation, and so that's why we're hopeful that this could be one of the potential expansion of the label that could go into first-line PTLD, not only second-line PTLD, when there is this CNS expression.
Help us to understand where you stand with manufacturing for your portfolio?
So, as you know, we had always relied on CDMOs, but also, a few years ago, on internal manufacturing. Back in 2022, we decided to externalize company manufacturing, because when you are in allogeneic cell therapy, you don't need to have permanent manufacturing when the patients are, in demand, because you have inventory. You just use your inventory. So you make these allogeneic T cells like monoclonal antibodies. You make campaign of manufacturing that allows you to have an inventory ready for use, and then once your inventory is, being used, you start to replenish it through additional campaigns.... So that's clearly showed to us that in the business model for allogeneic, which is very similar to the business model for monoclonal antibodies, you don't need to have your internal manufacturing.
You can rely upon good CDMOs that allows you to make the manufacturing you need when you need it, and then manage your inventory. And that's what we're doing with tab-cel. That's also what we're doing with allogeneic CAR Ts. We use two CDMOs, Charles River and FUJIFILM Diosynth. In fact, FUJIFILM Diosynth is using for the manufacturing of CD19 CAR T of ATA3219, as well as tab-cel, the facility that used to be the Atara facility. We sold to them the facility. That decreased overhead. We get $100 million at the time of cash. That allows us to have access to the manufacturing we need when we need it, and we have a long-term strategic agreement with them to get this capacity of manufacturing, but just when we need it. We don't need that permanently.
You used to have a pharma partnership for your oncology vertical. Help us think about your plans going forward with regard to partnerships.
I think we are very open to potential partnership. At this stage, we see three possibilities. One is, we have this allogeneic CAR T platform, which, for which we will have data very soon, that will hopefully confirm what we've built, which is a potential best-in-class. This platform could be amenable to different type of development, different type of targets beyond CD19 and CD20 we just discussed. And we've had discussion with some companies that are interested to potentially leverage our platform to be able to target new type of tumors. Could be solid tumors, by the way, it could be liquid tumors as well. So we'll be open to this type of partnership. Now, in the autoimmune field, maybe at some stage it will be important to be able to expand further beyond lupus nephritis and SLE.
What we have in mind that next year, when we have the first data and we clarify the dose, especially with our lymphodepletion, then we can expand that, maybe with some partners, expand that further and be able to go in many, many more type of indication. We can go to multiple sclerosis, where we have great experience, and when we have a great product in that case, we could go to other type of B-cell-related type autoimmune disease, such as myasthenia gravis, such as myositis, and even rheumatoid arthritis, because there have been some interesting data recently shown by Dr. Schett, again, with using that case a bispecific, not an autologous CAR T, that shows that patient with RA could benefit from this type of B-cell depletion.
So this is a very huge field for a biotech company, and so partnering might make sense at the time. And the last one is, we have an EBV vaccine candidate that we've been doing at some collaboration level with our partners in Australia at QIMR, and that's certainly something that we don't want to develop by ourselves. So we are in discussion with some companies on that EBV vaccine, which could be an interesting additional value-creating catalyst for us.
One last question here. Speak to your technology platform again and the moat that is built around that in the context of almost this kind of matching technology that you have.
Yeah. So we, we have that technology, and the amazing things about Atara is, on one hand, we are entering the clinic with this allogeneic CAR T, but it's based on an experience that we have with tab-cel and even ATA188, where, as we said, we have treated 600 patients. So we know how to manage all the supply. We have scaled up the technology already, so it's not that we have to scale up. We already have scaled up the technology. So we know that we can make this allogeneic CAR T for a few thousand dollars of cost of goods once we are at commercial stage.
And that's very exciting because we know how to manage the supply, how to manage the cost of goods to create a truly differenced, differentiated type of technology that could really answer the medical need and the business need. Let me explain why I differentiated the two. The medical need is very clear, like what we see in autoimmune disease. There is a medical need to have this type of potential of drug-free, symptom-free period with a full depletion of B cells in these patients, and that has been shown with autologous CAR T. So there is a medical need there. There is a medical need in lymphoma as well, where the current product, a CAR T that exists, that are autologous, and even the allogeneic one, are just able to get about 40% CR at six months, complete remission at six months.
That means 60% of the patients are not able to get that, so that's a large number. Autologous CAR T are not adapted to large population. In fact, the most advanced autologous company, Kite, has just been able last year to treat 6,000 patients, even though they've been 7 years in the business and invested millions and millions in manufacturing. Only 6,000 patients. So there is no way that autologous CAR T, we believe, can really address the medical need of autoimmune disease. When you think that this, we're talking about hundreds of thousands, millions of patients, there's absolutely no way autologous CAR T can address that. Allogeneic is, we believe, the future there. So that's the medical need.
But the business need is also important because, as I said, it's not only to have a product that is truly off-the-shelf and made at a low cost of goods of $a few thousand, but a product that can really be used in a way that simplify the use for the patient, the convenience for the patient. Our dream, our vision will be that we can treat autoimmune disease with ATA3219, without lymphodepletion, and with a good safety that allows to treat patients in outpatient clinic. It's not yet proven, we're just entering the clinic, but that's the vision we have, that to have, ATA3219 as easy to use than a monoclonal antibody, but having a much more profound B-cell depletion with good safety to allow for reset of the immune system, and therefore, a long-term impact on these patients.
Great. Well, with that, Pascal and Cokey, thank you so much.
Thank you very much.
Thank you.
Thank you all.