Earnings Call: Q1 2019

May 9, 2019

Good morning, ladies and gentlemen. Thank you for standing by, and welcome to the Atara Biotherapeutics First Quarter 2019 Financial Results and Corporate Update Conference Call. At this time, all participants are in a listen only mode. Later, we will conduct a question and answer session and instructions will follow at that time. As a reminder, this conference call will be recorded. I will now turn the call over to Doctor. John Craighead, Vice President of Investor Relations and Corporate Communications of Atara Biotherapeutics. Please go ahead, sir. Thank you, operator. Good morning, everyone, and welcome to the Atara First Quarter 2019 Financial Results and Corporate Update Conference Call. Earlier this morning, we issued a press release providing an overview of the company's Q1 2019 financial results and recent operational progress. Please note that this press release is available in the Investor and Media section at atarabio.com. I'm joined on the call today by Doctor. Isaac C. Hanover, President and Chief Executive Officer Doctor. Dietmar Berger, Global Head of R&D and Upal Kopikar, Chief Financial Officer. We will begin with prepared comments from Isaac and Dietmar and then open the call for your questions. We would like to remind listeners that the company's management will be making forward looking statements. Actual results could differ materially from those stated or implied by our forward looking statements due to risks and uncertainties associated with the company's business. These forward looking statements are qualified in their entirety by the cautionary statements contained in today's press release and the company's SEC filings. These statements are made as of today's date, and the company undertakes no obligation to update these statements. Now, I'd like to turn the call over to Atara's Chief Executive Officer and President, Doctor. Isaac Ciechanover. Isaac? Thank you, John, and thank you, everyone, for joining us this morning. We continue to make important progress advancing our T cell immunotherapy programs across 3 major value drivers: tab cel, multiple sclerosis and our next generation CAR T programs. On today's call, we will provide an update on our recent progress and upcoming milestones. In a moment, Doctor. Dietmar Berger, our Global Head of R and D, will discuss our clinical development programs in more detail. But I would like first to provide an update on the status of our ongoing tab cel Phase 3 studies for patients with EBV plus PTLD. Enrollment in these studies is proceeding slower than anticipated. The factors that make this condition challenging to identify and enroll patients in clinical studies are similar to other ultra rare and rapidly progressive diseases. We are aggressively implementing strategies to address these challenges that Dietmar will outline shortly and remain confident in our ability to successfully execute on our clinical development plan. As we have mentioned previously, we are also in discussions with the FDA and EMEA to align on a global regulatory strategy for tab cel. The objective is to align on a tab cel development plan for patients with EBV PTLD, which may allow us to potentially expedite a U. S. Regulatory submission. We are encouraged so far with our progress, and we expect the outcomes of these ongoing regulatory discussions in the first half of twenty nineteen. Overall, we view our tab cel pivotal development and regulatory progress to date as acknowledgment of the critical need to find new option to treat patients with this ultra rare and often life threatening disease. In parallel, we are continuing to advance our additional programs, including ATA188 and ATA190 for multiple sclerosis. We remain on track to present initial Phase I safety results for our off the shelf allogeneic ATA188 program at the Congress of the European Academy of Neurology, or EAN, in June of this year, with additional efficacy and safety results expected later this year. In addition, for our next generation CAR T portfolio, our collaboration of MSK reported positive Phase I clinical results for their mesothelin targeted CAR T immunotherapy for patients with solid tumors at the 2019 AACR Annual Meeting. Efficacy and safety results presented for patients with malignant pleural mesothelioma who have also received a PD-one checkpoint inhibitor and lymphodepleting chemotherapy exceeded our expectations. Following administration of a novel mesothelin targeted CAR T, MSK investigators observed a 72% response rate in a subset of these patients. These data are among the first proof of concept results for CAR T treat solid tumors. And given the strong fit with our next generation platform, we have prioritized development of mesothelin. We expect this to be our 1st CAR T program to enter the clinic with an IND anticipated in 2020. We are also excited for updated results from the MSK investigator sponsored mesothelin targeted CAR T study to be presented at ASCO in June. I would now like to turn the call over to Dietmar, who will provide a more detailed update on our clinical development programs. Dietmar? Thank you, Isaac, and good morning, everyone. As Isaac mentioned earlier, I would like to provide some additional detail on the status of our ongoing tab cel Phase 3 studies for patients with EBV positive PTLD. The factors that make this condition challenging to identify and enroll patients in clinical studies are similar to other ultra rare and rapidly progressive diseases. For example, the window for patient recruitment during the course of disease progression is short and the overall incidence of the disease requires a substantial number of study sites. As we advance our tab cel program, we continue to gain multi institution clinical experience and new insights about the epidemiology diagnosis, treatment and prevention of EBV plus PTLD. These insights were not available when we initiated our studies. As an example, this wide variation of PTLD incidence rates depending on many factors in the transplant setting, including the transplant type, level of immunosuppression, patient age and local standard of care at the transplant center. We have gained experience regarding these components during the conduct of our clinical studies based on our work with leading physicians in the area and from interactions with EBV plus PTLD patients and their families. At the same time, our experience confirms that the median overall survival in EBV positive PTLD patients following a solid organ or allogeneic hematopoietic cell transplant with failed rituximab therapy is short and PTLD is a life threatening condition with a high unmet medical need. Median survival in the hematopoietic stem cell transplant patient population is approximately 16 to 56 days. In the solid organ transplant setting, 1 year survival in patients with high risk rituximab refractory EBV PTLD is 36% with no patients expected to live beyond 2 years. We are aggressively addressing enrollment by continuing to open additional sites now with a number of 32 and leveraging our significant thought leader network to identify potential EBV plus PTLD patients as early as possible. We have further optimized our patient recruitment strategies over the last year, including earlier patient detection, outreach via social media and patient advocacy, setting up referral centers and close collaboration with key transplant centers in both the HCT and SOT settings. In addition, we continue to see strong investigator physician and patient interest as are frequently providing tab cel to patients in need under our early access and single patient use programs. We now plan to submit a tabcel European conditional marketing authorization application based on the initial Phase 3 results in 2020. This is based partially on our current enrollment trend, which now precludes submission by the last possible European filing window this year. But more importantly, we believe this updated European filing strategy provides flexibility to align on a tab cel development plan for patients with EBV PTLD with both FDA and EMA and to finalize timelines for a U. S. Regulatory submission. Again, we are encouraged with our progress and we expect the outcomes of these ongoing regulatory discussions in the first half of twenty nineteen. To ensure the integrity of the ongoing open label tab cel Phase 3 studies, the company anticipates disclosing initial top line EBV PTLD results following acceptance of the EMA regulatory submission. Moving now to our multiple sclerosis and next generation CAR T pipeline programs. We have made consistent progress on both as noted in our press release this morning. Our programs in MS are on track. We are advancing an off the shelf allogeneic ATA188 Phase 1 study in patients with progressive MS with initial safety results expected to be presented at EIM this June. We also plan to present additional safety data and initial efficacy results from that study at the Scientific Congress in the second half of twenty nineteen. In addition, we expect to initiate a randomized study of autologous ATA190 in progressive MS patients in the second half of this year. Turning to next generation CAR T immunotherapy programs, we are excited about our recent progress. Our collaborators at Memorial Sloan Kettering Cancer Center recently presented positive Phase 1 results for their mesothelin targeted CAR T immunotherapy in patients with pleural solid tumors at AACR in March. As Isaac mentioned, we were encouraged by the 72% response rate in a subset of patients and we look forward to MSK's presentation of updated results at ASCO in June. Based on the MSK data, we are prioritizing our development of a next generation mesothelin targeted CAR T immunotherapy with an MSK novel 1XX CAR signaling domain and the PD-one dominant negative receptor for patients with mesothelin associated solid tumors with an IND for this program planned in 2020. Using more physiologic T cell activation and targeted checkpoint inhibition offers the potential for a next generation CAR T cell approach in different solid tumor settings. Atara is expecting presentations highlighting tab cel and our next generation CAR T immunotherapy technology at ASCO 2019. I would now like to turn the call back over to you. You can go ahead and take your questions. Operator? Thank you. We will now open the line for any questions. We ask that you please limit yourself to one question and encourage you to reenter the queue if you wish to ask a second question. We have a question from the line of Anupam Rama of JPMorgan. Your line is open. Hey guys, thanks so much for taking the question. On PTLD enrollment dynamics, hey guys, thanks so much for taking the question. On PTLD enrollment dynamics, I think the press release said you have 32 sites open and you're planning on opening more. What are the timelines for this? And is there a regional focus here for site initiation? And then just another quick question on the Tuesday oral presentation for mesothelin CAR T, these data sound like they're going to be updated from AACR. So perhaps you can help us understand the scope of the new data we'll be getting. Thanks so much. Yes. Thank you, Anupam, for the question. With regards to PTLD and the enrollment dynamics, we are in process opening new sites, and we're also planning to extend the geography where the study is currently focused primarily on the U. S. We're planning to expand to other regions consecutively and aggressively. Looking at this, I want to point out that this is not the only activity that realistically and we're looking at a slew of recruitment strategies that we have started over the last year. Those look at earlier patient detection, outreach via social media, patient advocacy. We set up referral centers because sometimes these patients have to be transferred from one site to the other. And we collaborate very closely with key transplant centers in both the HCT and SOT settings. So we are confident that we will be able to execute on these studies. Regarding the mesothelin presentation at AACR, you're correct. This will be an update of the current data that we have seen at AACR. So we are expecting more details on the patient population, potentially more patients and Great. Thanks so much for taking our questions. Great. Thanks so much for taking our questions. Another question from the line of John Newman of Canaccord. Your line is open. Hey, guys. Good morning. Thanks for taking my question. So I'm just curious, I know you probably don't want to divulge details, but with regard to the work that you're currently doing with the Expanded Access Program, will you be able to incorporate those data into any regulatory filing with either the FDA or Europe? And to Anupam's question on the mesothelin CAR T, it does sound like there will be data from some additional patients. Just wondered if you could give us a sense as to sort of potentially how many? And then also on your IND filing for CAR T in 2020, should we assume that that's initially an autologous product? Thanks. So thanks, John. With regards to the first question regarding the early access program, our concept is to present the totality of data to regulatory authorities and the totality of data includes a broader set of experience, including our pivotal trials, but then also the Memorial Sloan Kettering studies that have happened over several years, obviously, and it also includes the early access program. From the early access program, and this was really an early access study also. From the early access program, you will also obtain safety and efficacy information and we have published some of that information on various tumor types actually at different meetings, the most recent publication being on leiomyosarcoma last year. With regards to the mesothelioma data, you're correct, we're expecting more patients. I cannot provide details at this point because the ASCO presentation is under embargo. But obviously, these are data from the ongoing study, and the study has continued recruitment as you know with the same pace that it did before. This is Isaac. So John, just one addition to the EAP to give you some color. Because this is a life threatening disease, patients who, for example, can't make it to a study site, we are sure at Atara that every patient who wants access to this drug to this therapy gets it. And so there are patients, for example, who do fall out. The timing is relatively short to some of these patients who are progressing in their disease. And so that data is important and will be part of our kind of the totality of information that both agencies look at. Great. And your final question regarding mesothelin, yes, initially, this is an autologous program with the objective to later on put it on to our allogeneic platform. Yes. It's very similar to what we did with the 188 program where we get our proof of concept for this next generation molecule with the 1XX and PD-one knockout, then we can then move very rapidly into making allo versions of it very similar to how we did the 190 program and then move forward to 180. We have another question from the line of Salim Syed of Mizuho. Your line is open. Hey, guys. Thanks for all the color. Really appreciate it. Just a couple for me. One on MS, given that I guess this now becomes the more important catalyst for the year given the delay in the PTLD. How should we be thinking about success of the Phase 1 study here? I know you guys have described this in the past as this being a high risk, high reward program. So any color on how investors should interpret the data when we get it? What do you define as a successful outcome here? And then the second question, just on the commercial opportunity of PTLD, Given the delay in enrollment in the clinical trial, is there any read across how you guys are thinking about the commercial opportunity in PTLD? Thank you. All right. Thank you, Salim. Regarding the MS study, once again, the BMS program is on track. We are presenting the safety data at EIN and the efficacy data, the initial efficacy data and additional safety later during the year. This is a safety study. This is a Phase I dose escalation study of the allogeneic program. We are excited about this because this is the first time that you have an allogeneic T cell immunotherapy in basically a neuro inflammatory disease, right? And a positive study at the initial data set will be, yes, it's safe. We can provide this to patients. We have a dose escalation setting. And then obviously, we're very interested in other endpoints and other outcomes. We're planning to present those at the later during the year. And we're looking at different types of endpoints, including the EDSS score, including brain imaging, including biomarkers, but these will be later during the year. And Salim, in regards to just the read through from the trial to the market, we think PTLD is a very important market for us and for patients. We have a therapy that has curative intent, it's cost effective and has a strong value proposition and a great read through by both physicians and patients. In addition, PTLD, as we said, is an ultra rare disease, and the number of patients that qualify for our studies is smaller. And as such, using the Phase III as a surrogate for ultimate market, I don't think, is not how we look at it. What we see is, with regards to the demand, both from our Phase III studies as well as the EAP and, as Dietmar mentioned, SPUs for patients where we'll have to send the therapy to their site that isn't associated with the trial. All that gives us a lot of comfort as well as the MSK experience of the previous data that you've seen in regards to the disease state and just the unfortunate outcomes to that occur in these patients who don't get this therapy. Hi, Selim. It's Uphol. I just want to add to what Isaac said. Dietmar alluded to this earlier on the call where we've seen a wide variation of EBV positive PTLD incidence rates. And there are several factors, right? So it's experience and standard of care of the transplant center, the type of transplant ACT versus SOT. There's variation in the organ type, the level up and the degree of immunosuppression and pediatric versus adult patients to the age matters as well. So what we do want to net out for you is that rates of HCT, SOT incidents that we've seen is in the low single digit range. It's blended across all these factors. And beyond PTLD, what we've seen from EAP and the EBV positive malignancies in the patients is tab cel is more than just PTLD. It's representing along with MPC a pipeline or product opportunity. Great. Thanks so much guys. Another question from the line of Matt Sykes of William Blair. Your line is open. Good morning. Thanks for taking my questions. So if I could start, I mean, you still say the regulatory discussions are on track for kind of concluding in the first half that you're pushing out the EMA filing by a year. So that would lead one to assume that the FDA maybe is not as interested in going for this faster approval and once more of a complete data set. And I guess my question is, can you define what you mean by initial Phase III results that determine you guys have used in conjunction with the EMA filing? Thank you, Matt. Let me take your questions one at a time. So, thank you, Matt. Let's take your questions one at a time. So we are currently in discussions with regulatory authorities, and I would call these regulatory strategy discussions. This is about the overall submission package, the totality of data. These discussions are progressing well. We had announced that we think it will be done by the end of the first half of the year. And we're still in that phase. We cannot update you exactly on those discussions at this point in time because they're ongoing, but we are encouraged by the progress of those discussions. Then regarding the timeline of the European submission, I want to point out that we have provided a wide range here purposefully and it's based partially on the current enrollment trend. You have specific windows where you submit in Europe specific acceptance dates they have. The latest EU filing window this year is in November, and we've realized very recently that the enrollment trend now precludes a submission by that latest EU filing window. But more importantly, right, this wide range is based on the ongoing discussions with the regulatory authorities in both the U. S. And Europe, right? The objective of these discussions again is to align on a global tab cel development plan and align on a global development plan that's really based on totality of data, including all the different data sources that we have, similar to the current plan that already exists for the conditional marketing authorization submission in Europe. As a potential result of these discussions, we hope to finalize the timing of our U. S. Regulatory submission and really to give you more of an update then by the end of the first half of the year. However, as these discussions are still ongoing, we provided this wide submission time frame in order to anticipate a range of possible regulatory discussion outcomes. The only thing I would add, Matt, is as Dietmar said, we provided this wide range in order to give us flexibility in regards to where the FDA discussions will net out. So I wouldn't make the conclusion in your question that this is already alluding to FDA commentary where they're not supportive. In fact, they've been very supportive with us, and that's why we feel comfortable that we'll be able to tell you in 'nineteen. Just at this point, we are in those discussions, and we can't make commentary around it. Yes. And actually, on the FDA breakthrough, right, and on the EMA Prime, you're actually encouraged to have these ongoing discussions with both agencies. And they've been supportive throughout the progress and they're really open to having those discussions. Regarding the subset, right, regarding the number of patients or initial Phase 3 results, the regulatory strategy is really based on this concept of totality of data, which means that you look at the overall experience you have, that allows you to submit based on a subset of data for the pivotal studies. As these regulatory discussions are ongoing, we cannot speak about exactly what that subset is, but the initial results that we will see are exactly that subset of a preplanned analysis. Got it. Okay. Thank you. And then regarding the mesothelin CAR, I mean, obviously, the data at ACR was very encouraging. When you guys move forward next year with your own next gen version, do you think you'll initially start with the local regional delivery for mesothelioma and the pleural cavity or would you go kind of right to IV and try to include some other mesothelin positive tumors? I know they're also, I believe, starting to look at triple negative breast cancer at MSK as well. Yes. We have not finalized our clinical strategy, obviously, and this is still under discussion. I want to say the data from MSK are intriguing and they are based on a local regional administration into the intrapleural space. So this is definitely an area that we will study. Besides that, we will obviously study the IV application as well. The preclinical data for the 1XX activating domain are really encouraging also the preclinical data that have been seen for the PD-one dominant negative receptor. That's what we're thinking that with a next generation product beyond the intrapleural application or the local region application? How can this product be applied also intravenously to other types of tumors? And you're right, breast cancer is one tumor, triple negative breast cancer, high unmet medical need, but also a subset of those tumors is mesothelin positive. But there's a variety of other tumors that we're thinking of, right? And if you look at the types of mesothelin positive tumors, they include pancreatic cancer, ovarian cancer, other types of diseases. So we'll have to think carefully about the development plan overall. Yes. The only other thing I would add, Matt, is that you can imagine, even in our own commentary, this current program exceeded expectations. So the bulk of the data is in mesothelioma patients, and that you should assume that that's going to be the center of where we take this therapy. The efficacy data is, as we say, intriguing. The safety data is the other important part that really differentiates this molecule. And demand and interest in this program has only increased with the publication at AACR, which is why we're going to have an update in June at ASCO. So I really I would say we're absolutely interested in broader indication than other administration sites, but intrapleural and mesothelioma as a primary should still be the core where initially this program will be developed. We have another question from the line of Salveen Richter of Goldman Sachs. Your line is open. Hi. Thank you for taking the questions. It is Mariana Boatman for Salveen. I have a couple. One of them is, you have mentioned the wide variation in incidence rates of PTLD and I was wondering if we could get a little more clarity especially as regards to the depletion protocols? And also how that sort of has different how that influences incidence rates in the U. S. Versus Europe and in the U. S. The sort of like MSK protocols versus West Coast protocols like how should we be thinking about that? Thank you. Yes. Thank you for the question. This goes into a lot of detail of the biology of PTLD. And eventually, what we are speaking about here is immunos suppression associated lymphoproliferative disease. There's also a recent paper coming out of Stanford that describes the disease really in that way. And there, obviously, the level of immunosuppression becomes really important. And this is where the T cell depleting programs around the transplant and any type of immunosuppressive activity actually become important. I'm answering the question that way because not only the T cell depletions, also the other types of factors that come together at the transplant center. Eventually, we're talking about the mix between prevention of PTLD, but then also treatment afterwards. We do see that the treatment paradigm is actually quite stable. But on the prevention side, some of those factors that you're talking about, for example, less intensive T cell depletion regimens or the use of post transplant cyclophosphamide as well as more aggressive monitoring and treatment of EBV positive ripenib with rituximab all play a role. The answer has to be broader because these factors are really different at the individual sites. And in some sites, you see an increase in the immunosuppressive regimens. In other sites, see a decrease and that then directly impacts the incidence of PTLD at that site. And we're learning as we go along and as we work with those sites about the exact factors at each specific site. When you talk about Europe versus the U. S, overall, the standard of care in the transplant setting is global with a lot of site specific variation. It's not even variation between Europe and the U. S. It's really site specific variation. And you find sites in Europe that exactly do their transplant as they do it at the Hutch and Seattle, and you find other sites that orient themselves more towards other U. S. Sites. And that variation needs to be taken into account. But overall, what we provided as like a median in the basically saying it's a low single digit low to medium single digit range in incidence across all the sites and across all these factors. That's, I think, one of our key conclusions. Got it. Thank you. Thanks for the color. And I had another question on the next generation CAR T. There were prior trials where mesothelin CAR T were used at National Cancer Institute. And I believe the response rate was fairly low. I think they were not done in the presence of immunosuppressants checkpoint inhibitors. I'm wondering how do you explain the difference in response rates that MSK has gotten versus NCI? Yes. Thank you for the question. There were obviously different studies that we're looking at mesothelin targeted therapeutics. I think there are various factors here, right? One is, this is a different product, right? This is a different mesothelin targeting domain, a different SCFV that has been very carefully selected. And I think that SCFV and we have licensed that SCFP is one key component. And really, we're talking about direct binding and the different binding and characteristics and specificity of that specific Fcfe. And the other factor here is this is intrapleural administration. I think at this point in time, we don't know eventually what the intrapleural pleural administration does versus the IV administration. But you definitely achieve high cell doses at the site of the tumor when you give the cells intrapleurally. And then the addition of the checkpoint inhibitor may play a role. Obviously, the checkpoint inhibitor in itself, there are studies with checkpoint inhibitor alone that give you a specific response rate. The studies that MSK has been demonstrating obviously had much higher response rates than what has been seen in these earlier trials. So we're not talking about an effect of a checkpoint inhibitor alone. We're talking about an effect of checkpoint inhibitor together with cells because you're really maintaining activity of the cells, you're adding to the persistence, you're unleashing the T cell component eventually with a checkpoint inhibitor. So there are various factors that are different. Eventually, what really counts for me is the clinical efficacy and the observation that has been seen in those patients, and this is obviously very encouraging, and we will follow through on that. The only thing I would add to that last comment is it's still a small subset of data, but we know what a baseline of the PD-one inhibition does in this condition. And so the additive effect of the combination is clear. We've also had or MSK has had experience single patients where response rates were even seen before the PD-one was administered. And so the synergy of the 2 and also our addition of the P1 knockout in the next generation, I think, is what ultimately is a factor in really differentiating this product from prior programs. The other key component is, we can talk about response rate, but safety is also the key issue in all of this. Those earlier studies as well as other studies really were even able to achieve efficacy because the product itself wasn't tolerated. So from one of the things that we're really intrigued by this program is the ability to actually administer this and give multiple doses to patients over the long period of time, because in these conditions, I think that's necessary in order to get a durable response. Got it. That's very useful. Thank you so much. We have another question from the line of Mark Frome Cowen and Company. Your line is open. Hey, thanks for taking my questions. Can you guys provide some metrics maybe on exactly kind of where you are on enrollment? And then you mentioned opening more sites. So kind of like where would you like to be? Is the right number 40? Is it 50? What's the right number of sites over maybe the next 6 months? So we cannot comment on the exact status of enrollment and the patient population in ongoing open label Phase 3 study and we haven't done that before. For the additional sites, we're now at the number of 32. We have really not spoken about the overall number of sites that we're looking at. And by the way, that number is changing, right? And we realize that enrollment is still obviously you add more sites. We're currently in the process of adding more sites, and we will also expand the geographic footprint beyond the U. S. And then we think that adding sites, for example, in Europe will be another key factor that allows us to recruit really more expeditiously. And we're also far along into our into this study, right? So as we mentioned, the European submission had a cutoff date of November simply because that's the last date that they're willing to accept a submission. And so with additional sites, these are all planned for us. We were obviously increasing the numbers, but we're far along into the study that I think a lot of the other aspects besides for site additions like advocacy, outreach, trying to identify the patients when they first develop PTLD. So really try to create the backlog earlier on because when ultimately, it's time to give the therapy, That window is relatively short. And so we've taken really a proactive approach to identify patients really early that may become eligible for the study or the EAP program. And that active surveillance is a really key part of what we're doing to ensure that the study is still we're able to complete them in a timely manner. Okay, great. And then turning to the MS program, can you just remind us of kind of the dose escalation scheme that you're using in 188 and kind of when we get these data updates first at EAM, but then also in the second half when we start to see efficacy data, how those doses compare to what was seen before with 190? Well, we are currently in thanks for the question. We're currently in the dose escalation phase. Obviously, details will be at that EAN abstract. But if you think about this just from a general perspective, we have published data together with Michael Pender, right, on the autologous 190 program. Those data were generated at a specific also initially dose escalation, but then final dose of T cells per patient, right? We started our study and that's what you would do with an allogeneic program. You start at a lower dose and then you escalate basically to that dose and potentially even beyond, right? And you will see that data at EAN. What's really important with all of this then obviously is in the progressive dose cohort expansion is how the safety turn out, and that's what you will see at EAN. But we're covering a range of doses, and you will see data on a clinically relevant dose. Okay. Thank you. We have another question from the line of Mary Raydock of Jefferies. Your line is open. Hi, everyone. Good morning and thanks for taking my questions. First one is just on tab cel and the EBV PTLD trial. I'm just wondering if you can provide more color on whether it's a number of patients out there that's lower than expected or whether it's more weighted toward not getting to the patients soon enough to give them treatment? Thank you for the question. It's always a mix of both, right? Now eventually PTLD is an ultra rare disease. And then we're talking about a pivotal trial here, where we usually try to and we are to have a homogeneous patient population. So the number of patients for the trial is even smaller. What makes this especially challenging and what we've also learned is that it's a rapid progression, right? Once patients are identified for the trial, you need to be able to provide treatment very, very rapidly, which means you don't have the time to open an additional site for a patient that is coming off, right? You need to have the site open or you have to transport the patient to another site, right? The median survival of patients in the relapsedrefractory setting after HCT is 16 to Physicians identify the patient. They come to us. We need to deliver really quickly. Eventually, that is also why an allogeneic product makes so much sense for these patients because you don't have time to think about other treatment approaches. You have to be able to deliver a product within 3 to 5 days as we want to and as we can do with tab cel, with the allogeneic product. So that value proposition is absolutely there. And the fact that you see all those requests for the early access program, the fact that we have an NPC study, the fact that we're planning for a basket trial, really that explores the overall, I want to say, value and market opportunity for tab cel. Got it. That's very helpful. And then just as a follow-up to that, I'm wondering if you're noticing any differences between SOT and No real differences in the No real differences in the study. Obviously, if you look at the epidemiology, there's more solid organ transplant cases, which means there's also more opportunity to have PCLD. Also in the solid organ transplant setting, it's very dependent on the organ type and the PTLD occurs basically with a delay because you've got these years years of immunosuppression. So you can see PTLD in very different settings in the solid organ transplant arena. Right here, you can see it either at the transplant center or you can even see it at community sites where those patients are treated over the course of like the long term follow-up of their transplant. And that's another key learning for us, right? What are the sites that you need to go to? How do you approach, for example, these community centers? How do you include them? That's where we get to this concept of referral centers, right, where we then can treat PTLD. So there's a lot of de learning. And there are slight differences between HCT and SOT. Eventually, I want to point out though PTLD is PTLD is PTLD, right? The biology of the immuno depression associated with lymphocytic disease is the same in these different areas. And the response to tab cel is also very similar in those different areas. Got it. Thank you. And last question is on the mesothelin program. Pretty interesting that you guys are administering intrapleurally or that the therapy is being administered intrapleurally and you're seeing such a nice efficacy. And I'm wondering if that route of administration, if there's understanding that that's making a big difference with having the cells trapped in that area, and if you can comment on that. Eventually, the answer to this had to be, we don't know, right, because nobody has ever studied the intrapleural versus IV, so that you could really come to a comparison. But obviously, we have these very positive data with the intrapleural administration, with the additional checkpoint inhibition and with the specific product that they use with a specific binder, the specific Fcfe. So we will follow-up on this and all this will go into how we design our development program for the 2nd generation product. Got it. Do you have a sense of whether you're getting better than expected persistence based on intrapleural delivery, I guess? Yes. Some of the specific data were already at AACR, right? And Prasad Adesumelli, the investigator, was demonstrating that he does see mesothelin targeting CAR T cells in the circulation for an extended period of time. So he was at that point in time interpreting that as better than expected persistence. We'll potentially see updates of that at ASCO as well. This concludes our question and answer session. And I will now turn the call back over to Doctor. Isaac Sihanover for closing remarks. Thank you. I want to thank everyone for taking the time to join us on the call today. I also wish to acknowledge the many extraordinary contributions by Atara employees that enabled us to reach this point. I have the utmost confidence in our team to achieve many important milestones ahead. And when a new CEO is named, he or she will be in a great position to further realize Atara's mission to transform the lives of patients with serious diseases. Thank you all.