Good morning, everyone. My name is Pascal Touchon. I'm the CEO of Atara Biotherapeutics. A pleasure to be here, and thank you, JP Morgan, for inviting us to present today. After the usual forward-looking statement, I'd like to really spend the next few minutes detailing why Atara is in a unique position in the allogeneic cell therapy field, not only with the fact that we are the first- ever to have delivered on the transformative potential of allogeneic cell therapy with the approval of EBVALLO in Europe in December 2022. This is the first- ever and still the only allogeneic T-cell therapy approved in the world, in that case, for the treatment of post-transplant lymphoproliferative disorder.
Very exciting milestone that we achieved some months ago, and now we are busy putting together the BLA submission for the U.S. FDA that we expect to file in Q2 of this year. That's very exciting because we can then bring tab-cel, EBVALLO in Europe to American patients on top of having brought that to European patients with our partner, Pierre Fabre, in Europe. Now, we've expanded also recently the global partnership with Pierre Fabre, and I'll give you more details about that in a minute. That's important for us to be the first-ever company to bring an allogeneic T-cell therapy to the market because it's also helping our ability to develop further assets or other product that benefit from our knowledge or know-how or expertise in bringing a product to regulatory approval, where we can accelerate the development of this product.
I'm talking here about allogeneic CAR-Ts, and in particular, ATA3219 or allogeneic EBV CD19 CAR-T, which has unique features, unique aspect of its design that we believe can create a potential best-in-class in not only hematological disease like lymphoma, but also in autoimmune disease. Most recently, we have focused our activities on tab-cel, on our allogeneic CAR-T, and streamlined the operations and activities with a strategic restructuring, which is helping us to have now cash- runway into 2027. So three years of cash ahead of us, which give us the time to do a lot of things that I will explain in a moment. Now, let me spend a few minutes on our partnership with Pierre Fabre. We are extremely pleased of this partnership.
Pierre Fabre is an amazing partner for a biotech company and has now launched a product, EBVALLO, in Europe. But most recently, we closed the deal at the end of September-December, which is a global expansion of that partnership with Pierre Fabre, where now they have the global rights for the product, for tab-cel, and the most important focus will be the launch in the U.S. following, hopefully, BLA approval. Now, that deal is based upon having not only a very significant level of upfront and milestone, reaching $640 million for that expanded deal. So this is in addition to the European deal, where we had already significant upfront and milestone. At the same time, we have significant double-digit tiered royalties for the future sales of the product.
So we think it's a win-win situation on that deal between Pierre Fabre and us to be able to benefit from the value that we have created for patients and our shareholders with tab-cel, now reaching, hopefully very soon, American patients. Now, we receive at the close about $27 million, which was a mix of upfront and purchase of inventory, and we are now moving into this preparation for the filing of the BLA in Q2. We've hopefully the ability to get some priority review as we have a BTD status. We do hope that the FDA will look favorably at our submission from that point of view. But let's see that in the next few months when we can announce the BLA acceptance, hopefully.
Now, on top of paying these upfront milestones and all these future royalties, Pierre Fabre is also supporting us in terms of the expenses to bring tab-cel to American patients. So they are reimbursing us with global development expenses, regulatory expenses, and a few other process development. And they're also acquiring the inventory as we make the product with our CDMO, CRL, and FUJIFILM Diosynth. So not only this is helping us from a milestone point of view, but also from a reimbursement, of course, point of view. And in total, the regulatory milestone between now and the BLA approval, including the BLA approval, will be $100 million, and that's going to help us in terms of cash- runway and in terms of having the money to invest in future value- creation for our allogeneic CAR-T portfolio.
Substantially, after we got the BLA approval, we will be transferring nearly all the activities on tab-cel to Pierre Fabre. So I mean by that, not only the clinical development, the regulatory, the manufacturing activities, which means that then Atara will be really a very focused allogeneic CAR-T company with, at that time, hopefully in early 2025, already some exciting clinical data coming from our development of allogeneic CAR-T in lymphoma and in autoimmune disease. On tab-cel, we feel confident right now about our BLA filing, and the reason is that we've had good alignment with the FDA on the CMC aspect a few months ago, which allowed us to do a new data- cut for pivotal study called the ALLELE study.
It's the study in second-line PTLD, and with this new data- cut, we were able to show a very impressive 49% objective response rate through IORA. That's extremely impressive because these patients are in second-line PTLD. They just have a few weeks to a few months to live for most of them, because the median OS is just three to four weeks when they come from HCT type of PTLD, and it's just a few months, up to four months, when they come from SOT setting. So we have a very serious, rapidly progressing type of disease here with that second-line PTLD, and here we have the ability, hopefully, to give up to 49% objective response rate in these patients.
Now, safety was very consistent and favorable as before, and at the same time, we have the consistent result in terms of estimated overall survival and in terms of duration of response. I will also highlight that the significance of this 49% is very clear, with a very, very low P value of 0.0001. So all good for the submission from a clinical point of view, and we look forward to our interaction with the agency very soon. Now, separately, in December, we also presented some exciting data in a very specific part of the patient. About 10%-15% of the patient with PTLD have a CNS PTLD, and these are very difficult patients to treat because most of the current treatment of lymphoma, such as anti-CD20 antibodies, do not cross well the blood-brain barrier.
Here we have a level of efficacy with nearly 78% objective response rate and significant overall survival that is really a change, a big game changer for these patients that are affected by this disease. This is also important because it was the first time we started to present data from our multi-cohort study, where one of the cohorts, which is looking at label- expansion for tab-cel, is specifically looking at CNS PTLD, and in particular, first-line patients. Exciting data that are going to come later to regulatory authorities once we have achieved the first approval in the first indication, which is second-line PTLD.
Now, tab-cel is important not only because it's a product that now is approved in Europe, going to be submitted in the U.S., going to create revenue for the company and for our partner, Pierre Fabre, but it's also the backbone of our technology and our platform, where we have started with tab-cel to approach EBV-associated disease such as PTLD and other cancer through a product that is an EBV-specific T- cells. Now, what we're doing now is to add another target to this type of cells in transducing a chimeric antigen receptor, which allows to have an allogeneic EBV CAR-T, where the main target then is linked to the chimeric antigen receptors.
This allows us to benefit from all the property of the biology of EBV-T cells, which are extremely able to traffic, to persist, to expand, but then to have a new target for oncological disease, hematological in particular, as well as autoimmune disease. Now, we have two products on which we are focusing our attention right now and our resources. One is ATA3219, which is an allogeneic EBV CD19 CAR-T. The other one is ATA3431, which is an allogeneic EBV CD19/20 CAR-T, so dual target from that point of view. We are approaching these two products with one going to the clinic right now in immunological malignancies as well as autoimmune disease, and with a particular focus on lupus nephritis, and the other one being in IND-enabling studies.
Why do we believe that this is addressing in a very different way the market need and the medical need? We believe so because we have optimized all the different features of the product, whether it's for ATA3219 or ATA3431, to be potentially best in class. What we are doing is to address what are the limitations of current allogeneic approaches, be they around gene-edited alpha beta T- cells, be it around gamma delta T- cells, or being around NK allogeneic CAR, because the all of these products are really having limitations in how they can deliver a service to patients and create some interesting market opportunities. In particular, the fact they are not persisting. They are persisting for just a few weeks, and they require very heavy and prolonged lymphodepletion to try to persist a bit longer.
That, we believe, is leading to lower level of efficacy, in particular, less durability of remission. Here we have a product at Atara, a product type of platform, which is really trying to optimize all the elements that will ensure safety, efficacy, and persistence, hopefully leading to durability of remission. Let me detail that for you very rapidly. You can see on the left the way we are designing this allogeneic CAR- T, where we are in fact maintaining the endogenous TCR, because that's the EBV TCR, and we know from different clinical study that this is leading to more persistence of the T-cells in patients. At the same time, we are doing a partial HLA matching, which is something we know how to use. We've treated more than 500 patients with our platform so far of allogeneic EBV T-cells.
So doing partial HLA matching has benefit together with the endogenous TCR in terms of persistence, in terms of safety, and avoiding GvHD in particular. And then we are using a very unique, newly developed type of, costimulatory domain called 1XX. It was invented by Michel Sadelain at MSKCC, and this is designed to allow more functional persistence of the T-cells, because it's been designed to avoid the exhaustion of the T-cells once they are infused into patients. And then we also optimize our manufacturing process to have more of a memory- phenotype in the final product, which has been proven in the clinic to lead to more persistence of the cells and more efficacy of the cells and good safety. So you see how we are optimizing all the different elements.
The reason we're doing so is because we've learned from what others have been doing. We think that the fact that you don't see any product today truly as allogeneic CAR- T or NK cells in pivotal study, despite many years of development, is because none of them has been able to be superior to the autologous CAR- T. Most recently, some company decided to stop their development in third- and fourth- line type of lymphoma because they don't have a competitive product. That's really interesting to see how ourself, instead of having to design several versions of the product, we decided to optimize the first version that is going to clinic right now. Now, we are also supported by three key clinical type of data.
In fact, each of the items, each of the features of our product, have been used separately in a clinic by leading teams in the field of CAR-T. We have, of course, 1XX, the signaling domain that has been used in autologous CD19 CAR-T and showing extremely good efficacy with up to 78% CR, and also this being achieved with very low dose, only 25 million cells per patient, which is in fact 10 times less than a typical dose of an autologous CAR-T. You give less cells that are more potent, more persistent, and you get very high- level of CR. That's 1XX by itself that has enabled that particular product, TAK- 940, to be that effective.
We also benefit from some data, academic data, preliminary data, in the clinic, in NHL and other type of B-cell malignancies, through an allogeneic EBV CD19 CAR-T. And that's an MSKCC study that they presented some update at ASH last month that shows that they have a very, optimal type of durability of remission, with significant, overall survival at three years in patient post-transplant with advanced B-cell malignancies. So again, an evidence that from a safety and efficacy point of view, you obtain good safety with allogeneic EBV CD19 CAR-T, at the same time you have long durable remission. And third, but clearly important, the phenotype.
We believe, based on the data from YTB 323 that were presented a few last year, in fact, at ASH, that optimizing the memory- phenotype in a final product will lead to more persistence of the T-cells, and therefore durability of remission. And here, that particular product from another company as an autologous CD19 CAR-T, just working on a memory- phenotype, was able to be very effective with 69% CR at six months and delivering only 12.5 million cells per patient, which is 20 times less than the typical autologous CAR-T dose. So what we're doing is to bring all that together in one product, and we are the only one to do so. We use three validated, clinically, optimized type of features to put that everything into one product, which is ATA3219.
The same applies to our CD19, 20, 3431. Why do we believe that we have here something that could create value for shareholders and for patients? First of all, in lymphoma, in hematological malignancies, there is still a huge medical need that is not satisfied. What I'm saying here is that the fact that when you look at what's happening in the U.S. today, out of about 15,000 patients that are eligible for CAR-T, autologous CAR-T that have been approved, only about 10%-20% of them are receiving CAR-T. And out of this 10%-20%, only 30%-40% will have complete remission maintained at six months and beyond.
So that's clearly a medical need that is unmet, because that means a vast majority of the patients either do not access CAR-T or have a very short type of effect of the CAR-T, and certainly non-long durable remission beyond the six months time frame. So here is a need, and of course, there have been a lot of product being developed to address that need, be it bispecific or allogeneic cell therapy. But I said earlier, these are creating some either issue in terms of durability or remission, or sometimes safety issues as well, which are really not enabling a full use of this type of product. And our aim with ATA3219 is to develop a product that is potentially best in class in achieving full safety and long-term efficacy, the ability to answer that medical need.
Now, the product, as I said, takes all these elements in one product, the 1XX, the memory- phenotype, and the EBV T-cell as a backbone of the product. We think based on our preclinical data, that we have element of superiority that are in being and to be confirmed in the clinical data. Here you see some preclinical data where we compared ATA3219 to an autologous benchmark, an approved product today that is very successful in the field of B-cell malignancies. You can see that not only we have in animal models, more persistence of the product, but we also better efficacy in the long- term. That's quite impressive to see this type of data at preclinical level.
Now it's up to us to move to the clinic in the next few months, and we have already an IND cleared for lymphoma, and we're going to—we are now enrolling patients as we speak. Now, the other aspect of our focus for ATA3219 is autoimmune disease. You're probably all aware that there have been some significant progress in that space over the last 18 months, with publication from an academic team in Germany showing some impressive result in lupus nephritis, and they updated their result at ASH last month with eight out of eight patients being in remission, some of them for up to two years after an infusion of autologous CD19 CAR-T. We have also seen some results in myositis and in systemic sclerosis, which show that there is really a new era.
It's in developing new treatment of B-cell linked type autoimmune disease, in having the use of CAR-T brought from hematological malignancies to autoimmune disease. Of course, what you need there is to be safe and to have the level of efficacy to be replicated in larger population and more diverse population. And that's really what we're going to try to do with ATA3219, where we have already good preclinical data, but we also a unique position on the data that nobody else in the field of autologous or allogeneic is having. That we have already treated with our backbone technology, with our allogeneic EBV T-cell, more than 130 patients with autoimmune disease, with very good safety.
I'm talking about ATA188, a product that was developed in multiple sclerosis, where we presented results that were negative in terms of efficacy a few months ago in 110 multiple sclerosis patients, following a study in the same type of progressive MS patient in 24 patients, a phase I study that was very positive. So in total, we've treated more than 130 patients, some of them for several years, many of them with several infusion of the product, and we had a pristine type of safety profile in these patients. So that's important because that means the backbone of allogeneic CAR-T has already been proven to be safe in autoimmune patients, patients that are fully immunocompetent.
Now, we're bringing the CD19 CAR on top of that, so of course, we still need to demonstrate that this safety profile is confirmed when you have the allogeneic EBV CD19 CAR-T. But that's a unique type of strength of our technology to have that experience in autoimmune disease that nobody else is having. The second product we're developing is ATA3431 right now, which is in IND-enabling studies. We hope to be able to file the IND next year, and that's a dual-targeting CD19/CD20 allogeneic EBV CAR-T, which is quite exciting because it could address some of the issue of the antigen escape and address the need for even higher efficacy.
I mean, whether with 3219 or 3431, the objective we have is to be best in class, which is to be much higher than the current 40% CR at six months being observed with autologous CAR-T, together with hopefully a better safety, because that's what will break the barrier of access. That's what will allow to have more patients being treated and a bigger market for this allogeneic CAR-T. Now, we're confident on 3431 because here again, in preclinical data, when we compare against an autologous benchmark, we have superior efficacy, and that's very clear from this very, very challenging Raji model, where we have CD19-null CD20+, where we can show very impressive level of efficacy in these animal models with our ATA3431.
As a conclusion, I'd like to clarify that the next few months, the 12-18 months ahead of us, are going to be very important from a catalyst point of view for the company, because not only we are moving ahead very resolutely towards the BLA filing, hopefully BLA acceptance, BLA approval, for tab-cel in the U.S., but at the same time, we are moving into the clinic in lymphoma with ATA3219, and we are planning to file an IND for lupus in Q1. Thank you very much for your attention, and happy to take any questions now.
Thank you so much for the presentation. I guess I can kick this off. Nobody else has any questions yet. I was wondering if you could speak a little bit more in detail about the concrete steps you're taking for the BLA submission for tab-cel and what the current market opportunity there is.
No, thank you for your question. So, in September last year, we had a very important step achieved, which was full alignment with the agency on the CMC aspect of the product. Not only the control of our product, the way we do the control in manufacturing and post-manufacturing, but also the way to define comparability between different manufacturing process versions. That was on the heels of the guidance from the FDA that were published in July of last year, which we believe we were able to influence in the way we have been engaged with the last few years with the agency to show them, because we are the first one to come with an allogeneic T-cell therapy, to show them how we believe we should demonstrate comparability between different manufacturing process version.
This has allowed us to then do a new data- cut for study, and following the time to get the independent review of the scans, we now have this data that are ready for submission. So we go through the pre-BLA meeting and then the BLA submission in Q2. That's what we expect. And then hopefully, if we can get a priority review based on our BTD status and based on the urgent need that these patients are having, because today there is no treatment for these patients. They are dying, and there is absolutely no treatment available. So we expect and hope to have some priority review, which will lead to possibility of getting this to the patient as early as possible, certainly in early 2025.
Now, the market opportunity is clear in the sense that this is an ultra-rare disease, that is a few hundred patients in the U.S., but at the same time, there is a lot of value brought by our product because we consider the benefit that we're bringing to patients being treated with something around 50% response rate. Once the patient is responding, is usually a long-term responders, and we have many studies that have been published from previous work that was done by MSK ourselves, that shows that you have survival at two years in the responders that is over 85%. So very impressive survival rate from these patients. So the value is there.
The value is there for the patient, for the families, for the physicians, but also for the healthcare system, because these are relatively younger patients, average age is 40 years old, and the healthcare system is investing a lot in the transplantation of these patients. Of course, the ability to have, half of them possibly surviving long- term is having a lot of value there for the system. And being ultra-rare, that means it doesn't have too much of a budget impact for the system at the same time. So we're very confident about the potential for price aligned with the value of the product at a high- level. We are very also hopeful because these patients are well identified. They are transplant patients. All the transplanters across the U.S. knows very well that there is a risk of PTLD related to EBV reactivation in these terms.
They are being tested for that. All the typical diagnostic tests are available for testing EBV, and that allows to identify these patients. Since these are second-line patients in our first indication, they are being identified at time of diagnosis, the time where they are being receiving rituximab or rituximab plus chemo. So the physician knows that if rituximab fail, which is the case in about 40%-60% of the cases, he's got tab-cel hopefully approved to answer the patient needs. Good identification of patient, relatively small number, but high pricing potential allows to have a significant business potential. That's just the first indication, because we are working also on a multi-center study looking at additional label- expansion for the product.
... Thank you so much. Super helpful. And then another question I had is in regards to CD19 CAR-T platform. Can you speak a little bit more about the competitive landscape? I know there's a significant amount of players there. Any differentiation and upcoming milestones for, for your company?
I think it's a very good question because sometimes we are being asked: Why do you go there? It's so crowded. It's crowded, but the crowd is not that effective. And it's interesting to see that after so many years of developing some allogeneic approaches, there is still no real pivotal study in place. In fact, there was one company having two pivotal study, and they just decided and announced a couple of weeks ago to stop these studies and go back to try to do earlier line of treatment, in lymphoma and do a new pivotal study that has not started yet. That's interesting because the reason I believe they did that is because they are not competitive. And you need to have a product as an allogeneic offer that is better than the autologous.
Better in terms of efficacy, ideally better in terms of safety as well, and then that will allow more access to more patients. That's our aim. The other interesting aspect that most of the other companies have done kind of iteration of development of the product. They started a clinical development with the first version. They say, "Oh, it's not that good, but now we're going to improve into having another version." So now they started again, first- in- human, with another version of the product with some so-called improvement. But all that takes time. What we did was different as a strategy. We decided to optimize the product from the beginning. So instead of having several versions of the product that goes to the clinic, we have one version, 30-90, but that version, we believe, is optimized to be best in class.
Thank you. And then one final question for me. Can you speak a little more in depth about your cash- runway and what programs you'll allocate this to, and any other details there?
Now, we have now really two key resource allocation focus. One is tab-cel for the BLA. Again, we want to accelerate that. We want to get that to American patient. I was talking earlier about the potential. We've said that we believe the peak- sales potential of that product across different indications in the U.S. is over $500 million of sales. And we have an agreement now with Pierre Fabre, where we have significant double-digit tiered royalties on that product, plus milestone, the sales milestone and regulatory milestone.
So we want to accelerate that because that will become a reality only if we get the progress that needs to be obtained, such as the BLA submission, the BLA acceptance, the BLA approval, and of course, the successful commercial launch, and we'll be working hand in hand with Pierre Fabre to help them to be as successful as possible for the launch in the U.S. So that's the focus of resources. Now, these resources are being supported by the FTEs and all external costs that we have by the cash we're receiving from Pierre Fabre in terms of not only reimbursement of expenses, but also in terms of the milestone. So that's really how we're going to focus on that, but at the same time, get the funding of our activities. Separately, in parallel to that, we have our development of allogeneic CAR-T.
We are moving into first-in-human study in lymphoma, in lupus nephritis with 3219, into IND-enabling studies for 3431, and that is being supported by the cash we have at hand, as well as the cash we're receiving and will be receiving, hopefully, from Pierre Fabre. Plus, we did a registered direct now a few days ago of $15 million from our top investors, who is really very excited about what we're doing on CAR-T, creating value there. And they're going to help us to make sure that we have enough cash to do this development that is starting right now in the clinic, and also the preclinical development, IND-enabling studies for the dual CAR-T.
So that is also linked with the fact that we have streamlined the organizations, and we thank, of course, very much all those that are departing Atara these few days. But it's really important that we can focus our activities and have the talent necessary to be able to develop a product. So that's why we can say we have cash into 2027. That means three years of cash. And that's very important because that means that early 2025, hopefully, we can get into the approval of tab-cel in the U.S. and start to transfer activities to Pierre Fabre. In second part of 2024, we may have the first clinical data on lymphoma, then of course, lupus on the CAR-T, plus the IND next year of ATA3431.
Basically, it means that in 2025, we will have a different company that is more allogeneic CAR-T focused only, with sufficient cash to go into 2027, maybe beyond, and at the same time, clinical data, so we can expand the activities on allogeneic CAR-T in lymphoma and B-cell malignancies, as well as in autoimmune disease.
Thank you so much. Any questions?
I have a couple of questions. So first one, so, I believe there's two company using the same technology, just like use EBV, BST. They failed.
Yes.
So what's your advantage over them?
I think we took a very different route. I mean, one company failed, and again, I'm not blaming them because they had to try different things. One company failed because they tried to develop a multi-virus product. They were trying to have in one product, the ability to address six different viruses. And I can tell you only one is already very challenging from a manufacturing and CMC point of view. I cannot imagine the nightmare of having to develop something that is equipotent on six different viruses. So at least we know one virus very well. We think this virus is very important, not only to address large number of EBV-associated disease, but also as a backbone for allogeneic CAR-T, and that's something we now control and manage quite well. But I think that was one of the issue that one company faced.
The other company faced a different situation, that they decided to go into, first of all, a very complex study in NPC that was not really easy to manage and administer, and spend a lot of money on that. And NPC is a very rare disease as well, where it was challenging for them to go there. And then the other aspect is they went into a particular allogeneic CAR-T, but with a target that is challenging because you have fratricide situation, and that therefore, it's very difficult to manufacture as well. So I'm not saying-- I'm not blaming them. I mean, they had to try different things. I'm just saying that we have a very, very different technology, and now again, we have a product that is approved, and that tells a lot about how advanced we are from that point of view.
Next question. So, regarding CD19 CAR treated a patient in autologous setting, those patients tend to be a relapse within one year. So how's your clinical data and how to mitigate this kind of risk?
We believe that there are two ways to mitigate. One is the fitness of the cells. That's why we believe the way we have optimized manufacturing and the different features of the design of our CD19 CAR-T is really to have better fitness of our T-cells that can persist longer, but not only persist, be functionally persistent. That means they can really traffic, expand, address the immunosuppressive environment in a way that allows them to have this long-term efficacy. Now, the other aspect is the antigen escape, and that's why we're developing the CD19/CD20, which we believe we can address from scratch, the possibility of antigen escape and the different type of balance between CD19 and CD20 type of presence at the surface of the tumor cells.
Okay, thank you.
Thank you so much. If no final questions, I think we can conclude the session. Thanks again.
Thank you all.