Earnings Call: Q2 2019

Aug 8, 2019

Good day, ladies and gentlemen, and welcome to the Atara Biotherapeutics Second Quarter 2019 Financial Results Conference Call. At this time, all participants are in a listen only mode. Later, we will conduct a question and answer session instruction will follow at that time. I would now like to turn the conference over to your host, Doctor. John Craighead, Vice President, Investor Relations and Corporate Communications. You may begin. Thank you, operator. Good morning, everyone, and welcome to the Atara's Q2 2019 financial results and corporate update conference call. Earlier this morning, we issued a press release providing an overview of the company's Q2 2019 financial results and recent operational progress. This press release as well as an updated investor presentation are available in the Investor and Media section of attarabio.com. I'm joined on the call today by Doctor. Pascal Tushon, President and Chief Executive Officer Upal Kopikar, Chief Financial Officer Doctor. Chris Hack, Chief Scientific Officer and Doctor. Ajay Joshi, Chief Medical Officer. We'll begin with prepared comments from Pascal and then open the call for your questions. I'd 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 the 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 would like to turn the call over to Atara's President and Chief Executive Officer, Pascal Tuchon. Pascal? Thank you, John, and thank you, everyone, for joining us this morning. Today is my first conference call as the Chief Executive Officer of Atara Biotherapeutics. It has only been a few weeks since I joined Atara in late June, but I have already been impressed by the expertise and commitment of our teams in developing T cell immunotherapies to transform the lives of patients with serious diseases. Indeed, I am confident that we are now in a strong position to execute on our commitment and create value for patients, physicians and shareholders across our tab cel, multiple sclerosis and next generation CAR T programs. What I would like to do today is first provide a brief overview on my background and tell you why I'm so excited about Atara's potential. I joined from Novartis, where I serve as Global Head, Celentene and Member of the Oncology Executive Committee. In this role, my responsibilities included the regulatory approval, pricing and reimbursement and global launch of Kymriah, the first ever CAR T approved globally in 2 indications. I was also leading Novartis global CAR T strategy, clinical development, manufacturing and technical operations and the financials performance of the oncology cell engine activities. Prior to that role, I was Global Head Strategy, Business Development and Licensing Oncology at Novartis and beforehand Executive Vice President at Servier, where I initiated the partnership with Selective and Pfizer on allogeneic CAR T. I believe my experience makes me uniquely suited to carry out Atara's mission to transform the lives of patients with serious diseases. I think work over the last 5 years in the field of autologous CAR T as well as 1st generation gene editing allogeneic CAR T, I believe cell therapy is a next therapeutic frontier in oncology and immunology following its transformative impact on patients with B cell malignancies. What excites me most about ATARA is that its T cell immunotherapy platform could have several important advantages over both autologous CAR T therapies and gene edited allogeneic CAR T therapies. Indeed, our allogeneic T cell therapies may be immuno privileged. They are obtained from healthy donors and do not require HLA edits, hence maintaining proliferation and persistence advantages. As they are matched for each patient for more inventory and available to patient within days, the treatment is more similar to prescribing and administering a biologic than the complex process of today's autologous CAR T cell therapies. Our epsilon virus or EBV specific platform can lead to therapies directed at EBV associated diseases like tab cel and ATA188 as well as allogeneic artery therapies. Our platform is already in clinical development for EBV associated post transplant liver proliferative disease or PTLD and other EBV associated disease including nasopharyngeal carcinoma and multiple sclerosis. We are also developing next generation CAR T immunotherapies for both solid tumors and hematological cancer. Our main priority here is our mesothelin targeted next generation CAR T candidate with initially AT82,271, an autologous version to rapidly achieve clinical proof of concept followed by the allogeneic version. With our unique innovative platform and our own state of the art manufacturing facility ATOM, we are creating a leadership position in T cell immunotherapy, developing truly transformative therapies for durable treatment effect, and I feel fortunate to lead such an innovative company. I would like now to discuss our strategic priorities in greater detail, starting with tab cel. As recently announced, based on discussions with the FDA, we now plan to initiate first in the U. S. A tab cel regulatory submission for relapsedrefractory EBV positive PTLD during the second half of twenty twenty. We're also in active discussions with the EMA to align on regulatory requirements and determine tab cel submission timing in Europe. The FDA has agreed to combine our 2 ongoing tab cel clinical studies into a single study called ALAELE. Both bone marrow and solid organ transplant patients are included with target enrollment of 33 patients in each cohort. The primary endpoint remains objective response rate. We also plan to conduct an interim analysis prior to initiating BLA submission. Now let's discuss the disease burden and market characteristics of this aggressive, often deadly cancer affecting a limited but meaningful number of allogeneic stem cell and solid organ transplant patients. There are no approved therapies for PTLD And this disease disproportionately affects younger patients with a median age of under 40 compared to about 65 for all lymphomas. Unfortunately, the expected survival after failure of the standard first line therapy of rituximab with or without chemotherapy is between 3 to 12 months in the case of SOT. In HCT, survival of the rituximab failure is about 1 month. In the U. S, we estimate that there are several 100 patients with EBV positive PTLD who have failed rituximab with or without chemo. This is a typical trial disease with significant unmet medical need. Given the severe disease burden of this condition, we believe tab cel has the opportunity to deliver a compelling value proposition to patients and health systems. First off, Tapcel has demonstrated in both Phase 2 and EAP studies that it has a high and durable treatment effect with objective response rates between 50% 83% and overall survival in responders at 2 years of over 80% in both HCT and SOT. Secondly, in these studies, we have observed few treatment related serious adverse events for tab cel in PTLD patients with no observed cytokine release syndrome or treatment related mortality. In addition, tab cel has a low administration burden with no pretreatment required, a brief IV push administration and only 2 hour post administration monitoring in clinical trials. Additionally, our order share T cell order match and supply management system is designed to deliver the treatment within 3 days. Beyond the significant business case in PTLD, we're excited about the potential of tab cel as an ultra rare disease pipeline in a product. Tab cel is an ongoing Phase II clinical development for patients with platinum pretreated metastatic nasopharyngeal carcinoma in combination with pembrolizumab. This is an EBV associated cancer with limited overall survival and therapeutic options. Incidence is high in East Asia, but even in the U. S. And Europe, there are hundreds of patients in need of better therapeutic options. Our 3rd tab cel opportunity is based on a multi cohort Phase II study that we expect to start in the second half of twenty twenty. We plan to enroll patients having other EBV related cancers with poor prognosis and for which we have some clinical experience from previous studies. This study could support potential registrational opportunities. Hence, the same product may progressively treat more and more patients in multiple ultra rare severe diseases. Turning now to MS program. We're also leveraging here innovative platform in developing the 1st EBV specific T cell immunotherapy in autoimmune disease. Our off the shelf allogeneic ATA188 program for multiple sclerosis is ongoing Phase I clinical study for patients with progressive MS. In late June, we presented the initial safety data of the first three cohorts cohort for ATA188 at the 5th Congress of the European Academy of Neurology. We saw no dose limiting toxicity and no treatment related treatment emergent adverse event at grade 3 or higher. We are dosing the 4th and final plan cohort now and expect to enroll a total of 24 to 30 patients in the study. The safety results also add to the overall profile of our allogeneic T cell platform with favorable tolerability in non immunocompromised MS patient as well as immunocompromised PTLD patients. Although designed to evaluate safety and tolerability in order to determine a recommended Phase 2 dose, the study also includes clinical efficacy secondary endpoint, including a number of established measures of physical, neurological and cognitive functions. We expect to report initial results on some of these clinical secondary endpoint at Xtrims in September as well as additional safety results. On the basis of the Phase Ia data, we plan to proceed into the randomized placebo controlled portion of the study. In parallel, we plan to initiate a randomized Phase 2 study of ATA190, an autologous version of ATA188 during the second half of this year to compare the efficacy and safety profile of these 2 EBV specific cell therapies. Last but not least, I would like to provide a brief overview of our next gen CAR T portfolio. We had a number of recent presentation at both AACR and ASCO earlier this year. What was most exciting for us were the 2 presentations by our MSK collaborators on the Phase 1 clinical study with their mesothelmine targeted CAR T immunotherapy in patients with advanced mesothelioma. Mesothelmine is highly expressed on cells in aggressive solid tumors, including triple negative breast cancer, ovarian, pancreatic and non small cell lung cancers as well as mesoteloma. In the latest ASCO presentation, a subset of 16 patients with malignant mesothelioma followed for a minimum of 3 months and receiving MSK MesoCAR T together with anti PD-one and NIFU depleting chemotherapy showed a 12 months overall survival rate of 80% and an objective response rate of 63%. We view these data as highly encouraging and have prioritized our mesothelin targeted next generation CAR T program ATA-two thousand two hundred and seventy one with a plan in collaboration with MSK to submit an IND for this program in 2020. Before opening the call to your questions, I would like to comment on our recent public offering. In July, we completed an underwritten public offering of $150,000,000 for the issuance of 6,900,000 shares of common stock and 2,900,000 prefunded warrants. These successful offerings transcend our financial positions and funds plan operation into 2021 for key milestone next year, including initiating the tab cel BLA submission and next generation mesoteline CAR T IND. I would like now to turn the call back over to the operator, so we can go ahead and take your questions. Operator? Thank And our first question comes from Anupam Rama from JPMorgan. Your line is now open. Good morning. This is Tessa filling in for Anupam this morning. Thank you for taking our questions and it's very nice to meet you, Pascal. So my question is on MS. With first efficacy data for ATA188 coming at Actharms in the coming weeks, Can you walk us through scope of data here and what the points of differentiation are that we should be looking for in the Phase 1 readout? Specifically, what are your expectations in the context of the disease for the key secondary endpoints that you will be outlining for us? Thanks so much guys. Thank you very much for your question. Will ask AG Yoshi to start answering that question. Sure. Thank you, Pascal. So just to put things in perspective, this is of course a study that is focusing on the progressive MS population. And really the focus in progressive MS is to delay deterioration. That's really the end goal. Now in order to assess that particular parameter, most parameters actually you need about 1 to 2 years of assessment to really prove anything. So our challenge in setting this study up was how do we get an earlier read than a couple of years, because as you know these data are going to be around 6 month data on a couple of cohorts of patients. We work with our leaders to essentially define multiple parameters that are in a well defined clinically meaningful essentially assess those parameters across multiple time points. What you're looking for across those parameters is basically similar change across multiple parameters at a specific time point. And what that and those and I should step back for just a second. So those parameters assess both clinical function, physical function, cognitive function. It's a variety of MS issues. If you see a similar movement in multiple parameters at a specific time point, that gives you confidence that there is a real signal there at an earlier time point than that 1 to 2 years that I was talking about. So success for us here would look like movement across multiple parameters at the time points that we describe when the data are presented. And just to add on that, I mean, XTRIMS is an important step in building up evidence in terms of safety and efficacy for ATA188. So then we can move to at a later stage when we have completed this Phase 1a study into Phase 1b. We expect to present initial efficacy results from the lower dose cohort as well as additional safety results from the higher dose cohort. The 4th and final planned dose cohort is almost fully enrolled, but we do not expect to have efficacy data available at the time on the 4th cohort at extremes in September. And this is just, as I say, a step. And we plan, of course, to progressively present additional data at Future Scientific Congress as data continue to mature. Other questions? That's great. Thank you very much. I appreciate the color. Thank you. And our next question comes from John Newman from Canaccord Genuity. Your line is now open. Hi, this is Chris on for John. Thanks for taking my question. We were just wondering, do you have any incremental color for us for how fast new clinical sites can be opened? And if you have any details, additional details on what you're doing besides that to help enrollment? Thank you for your question. I think, Eiji, you might want to start answering that question. Sure. So, in terms of speed of getting sites up and running, for PTLD, you're really looking at larger scale academic centers. So those you typically have a little bit of a longer lead time to open those sites. The reality for us is though that we've been building towards this for a while so much of that lead time is already built in. So we're starting to really see the benefits of getting those sites coming in because as you know academic centers often takes anywhere between 6 9 months to really get up and running. But again, we've done a lot of that lead in already. So we do expect to open up several additional sites in the U. S. Later this year. And in addition, we are opening up additional geographies because we just got we recently got a no objection letter from Health Canada. So we'll be opening up our 1st Canadian site later this year. And then looking forward to opening up European sites next year. In terms of any additional work that we're doing, much of the focus for us now is optimizing recruitment at the existing centers. And this has been really we've been leveraging a variety of resources, including medical times liaisons and other activities that I implemented in the past in previous lives in ultra rare indications. So multiple activities we've reviewed in ultrarare indications. So that way so I think again we've got we let me step back. Multiple activities from ulcerative indications that have been used in the past, including MSLs and including a variety of outreaches to both the patient advocacy community as well as, the established physician societies. And I have to say that one of my first priority when I joined was to look in details at the way clinical operation were run to make sure that we optimize our chance to accelerate recruitment in that very important study. I have been satisfied by what I've seen and that's why I am confident regarding the guidance we've given, which is of course linked with the enrollment in these studies. What we should say as well that some of the challenges that we faced here are linked with the disease itself. It's an ultra rare disease happily progressing where sometimes the patient cannot wait for the administrative burden of being recorded in the study. And that's why we're using our EAP program or SPUs as well to be able to treat these patients. Additionally, we have to recognize that there have been a number of competitive trials either directed at PTLD or basket protocol trials in this space that have been started over the last few years. And I think there are about 12 clinical trials right now in that space. So that's also something to take into account into enrollment, but it also tells a lot about the attractiveness of that particular medical need in terms of new innovative therapies. Got it. Thank you very much. That was very helpful. Thank you. And our next question comes from Salim Syed from Mizuho. Your line is now open. Yes. Hey, guys. Thanks so much and welcome, Pascal. A few from me, if that's okay. One on the MS program, curious how you guys are thinking about the risk that these T cells, they're going to be in MS patients, so they will have immune systems. So when you're looking at efficacy, like how do you guys think about the risk here that you're giving enough T cells so that they last, right? I know you can compare PTLD, but that was an immune system knockout patient. How do you how are you guys thinking about here that these T cells will be able to last enough to provide the efficacy that you're looking for? Number 2, just on ALLO program versus auto program, 188 versus 190. If there's any theoretical risk here of 1 potentially getting past the blood brain barrier more than the other or if there's a mechanism in place that the human body essentially would reject 1 ADA because it's not perfectly HLA matched? And then the last question is just can you provide more interim details on the tab cel program? What how many patients do you need for the interim and what would the ORR hurdle be? Thank you. Thank you very much. Ajay, do you want to start? Sure. So in terms of the persistence question, we have actually experience with EBV directed T cells, EBV targeted T cells in an immunocompetent population within nasopharyngeal carcinoma program. So as you know, in the Phase 1 studies at MSK, we had about 20% response rate in essentially an immunocompetent population. So we should be very well able to apply that concept to what's happening in MS because you've got a similar scenario, immunocompetent population using allogeneic T cells. So from that perspective, I think there's relative confidence that we should have enough persistence to get an efficacy signal and maintain efficacy appropriately. Do you want? Chris, do you want to comment on the blood brain barrier passage? Sure. I think here the tab cel experience is also a good guide in that our experience is that the EBV specific T cells have the ability to traffic. They cross the blood brain barrier and in our Phase 2 experience, we have observed several patients who've had CNS located PTLD to have objective responses. We expect that to continue as well in the setting of MS. And in previous American Society of Hematology presentations, we've presented on the activity of the antiviral T cell platform with essentially the same response rate observed in patients with CNS disease compared to those whose disease presented systemically. And on the auto and allo program in MS, A. J? And then, Faiza, would you mind repeating the specific question on allo versus allo? Now? No, I think you answered that question. I think the last question was just around the interim details. How many patients and what the OR hurdle would be? Sure. So as you might imagine, with any anytime you're doing an interim analysis and you're working on that with authorities, you're going to have to show substantial benefit and with some adequate level of certainty, which is essentially your ORR. The our current ORR, when you look at the total patient population, we have 33 patients. The null hypothesis is 20%. So our ORR would have to be 37 percent to meet the statistical hurdle. And as you might imagine, any interim analysis that we do would have to have a higher ORR statistical hurdle to meet the requirements. Okay, great. Thanks so much guys. Thank you. Thank you. And our next question comes from Matt Phillips from William Blair. Your line is now open. Hi, thanks for taking my questions and Pascal welcome, good to have you. You guys mentioned in the press release that 34 sites are now enrolling in the pivotal tab cel trial. So wondering how many of those can enroll both solid transplant and bone marrow transplant patients suppose maybe just one or the other when it was 2 separate studies, there was not I mean, a lot of them some of them were overlapping, some of them weren't. And then also just when can we get some disclosures on the enrollment of the trial? Do we have to wait until you guys say that you've submitted a BLA? Will we get some info? I mean, I think some disclosure on how it's going would be important given how long it's taken. Thank you. Thank you for your questions and for your welcome remark there. So on the number of sites, we say 34 that are unique sites, but of course, some of them are doing both. So we have about 23 sites for PHY0127 sites for PHY02 that are open for enrollment right now. And I think we as we said, we are going to increase this number of sites in the U. S. And following the CTA submission there. In following the CTA submission there. In terms of the your questions on the communication related to the enrollment, in such an open study, we have decided not to communicate on the number of patients being enrolled. And we will communicate on that at the time of the initiation to submission when we go into that phase of the development of the product there. What is important to have in mind is that we want to recruit the full population in both cohorts, even though we will do the interim analysis on a smaller number of patients. Okay. Thank you. And just to add on that, I mean, the just to be clear, we plan to communicate on our guidance. So when we say we will initiate BLA submission in second half of twenty twenty, we plan to communicate on that initiation at that time. Thank you. And our next question comes from Phil Nadeau from Cowen and Company. Your line is now open. Good morning. Pascal, let me add my congratulations on your new role. First question is on tab cel and the European regulatory discussions. Can you give us some sense of what elements still meet agreement between the company and the European regulators? Is it endpoints, enrollment criteria? Where is the debate? I mean, as you know, we've adapted amended our protocol for SOT and we have merged 2 studies together, the SOT and the HTT study in one study with 2 cohorts. So that's something that has been based on our discussion and constructive dialogue with the FDA. Now we need to discuss with the EMEA, forgot these changes and see how do they react to that and then what does that mean in terms of the timing of potential submission of a CMA. We are in a prime process, which is a very unique type of process for advanced therapies where you can have regular type of interactions with the rapporteur and then of course you may benefit for an accelerated review then. So we are actively engaged with rapporteur and other members of the committees to be able now to clarify when is the timing for EMA submission of a CMA. So it's really around this change in the protocol that is linked with all this kind of the FDA that now we need to discuss with the EMA. And do you have some sense when your discussions with the EMA will conclude? [SPEAKER JEAN FRANCOIS PRUNEAU:] It's moving rapidly. Cannot say exactly when it will be concluded. But what I can say that as soon as we have clarity there, we will make that as part of our public communication. Perfect. And then next question on the next generation CAR T. Can you remind us what is the difference between your autologous ATA-two thousand two hundred and seventy one and the mesothelin CAR T that was developed by Memorial Sloan Kettering and from which we have data? Yes. Chris, do you want to start on that one? Then I will explain our strategy there. Sure. So we're very excited at the opportunity to incorporate next generation co stimulation, 1XX, for example, as well as the T cell intrinsic checkpoint inhibition through the use of the PD-one dominant negative. And we'll be using the identical binding domain as has been used in the presentations given at AACR and ASCO. So we're using the clinically validated mesothelin binding domain together with the best available technologies as we advance the mesothelin CAR T program. I think the key here is that the binding domain, the SCFV is really unique. And in a sense that the data that we have presented the early initial data we have presented at ASCO and AACR clearly show a level of safety, first of all, and then efficacy that is not very common in mesothelin targeted type of therapies. So we have that SCAV. That's something that we are learning from the 1st generation CAR T development of our collaborators at MSK. And that same SCAV is being part of the construct of the next generation with the new costimulatory domain that is aiming at having the right balance between expansion and persistence of the CAR Ts. And then of course, we have added the PD-one DNR to have really a more physiological way of addressing the need to target PD-one and make sure PD-one and make sure that we have enough activity of the cells when they have penetrated into the tumor. Perfect. And then my last question is on the earlier pipeline. Is there any update on ATA 3,219, anti CD19 CAR T or ATA-two thousand four hundred and thirty one, CD19, CD20, CD22 CAR T? Yes. We are continuing this program, of course, with our collaborators there for the one you mentioned, which is looking at 3 targets there. And then so that's with Morfit, of course. And then for the CD19, which is a Nattara development, this development is progressing well. And as you know, objective here is really in a very well known type of CAR T targets to be able to show efficacy and safety that we are allowed to prove the concept of allogeneic CAR T based on EBV specific cells. So both programs are progressing. We don't have any special comment to make on specific type of achievements there, but they are progressing very well. Great. Thanks for taking my questions. Thank you. And our next question comes from Tony Butler from Roth Capital. Your line is now open. Yes. Good morning. Good morning, Pascal, and welcome as well. My question is around 188 in MS and Actrims. There are 3 questions. Number 1 is, you stated in the release that you were looking at progressive forms of MS, but yet in clinical trials, it's actually both relapse remitting and also progressive. So I'm curious what we get at Ectorum's directly? That's number 1. Number 2 is, while you clearly won't have any MR or there will not have been enough time for patients to have been on drug to see probably any changes in MRI. I'm simply trying to understand what could you present that would at least provide enough information that the T cells do have activity and more importantly are affecting the MS directly. I would appreciate some specificity there if possible. And then finally, did I hear correctly that there were patients or at least a patient that had PTLD MS that did clear. If that's true, could you please describe clinically how that was actually determined? Thanks very much. Sure. So this is A. J. Let me start with the 3rd question. So and apologies if there was any miscommunication or misunderstanding. There is no PTLD patient with MS that we are describing. I think what we were describing earlier is the concept that we have proof that the T cells do get into the CNS. They are able to cross the blood brain barrier and access the CNS compartment and exert function because we've had treated patients with CTLD, CNS PTLD. We've also treated patients in a slightly different setting with CMV retinitis and a variety of other CNS conditions related to CMV with CMV targeted T cells. So there's very good proof that these T cells that we create virally targeted access the CNS compartment well and exert their function. So that was the proof source for why we believe all of these cells are getting in to exert function for MS. So it's not really p telling. Hope that answers question 3. It does A. J. And thank you and my apologies for misunderstanding. No, no worries. No worries. Now getting back to first question on progressive versus relapsed or remitting. You're right. Our original thought process was to take a look at both. As we got deeper and deeper into the understanding of the autologous ATA190 program and what we wanted to focus in on this program, we specifically decided to stay targeted on progressive MS. And also it's really a progressive MS population that really doesn't have a lot of inflammatory disease. So when you mentioned MRIs, you're right, there's a lot of times you can get relatively early reads in active disease by tracking MRI status. But this is not active disease. We really want to focus in on the progressive component, which is where really most other therapies have failed to have failed. And we think that's the differentiator here. So for us, the win is the early win. There's an early win and a later win. The later wins are sustained responses on various disability measures like EDSS scores and time 25 foot walk test and whole brain volume reduction. But again, those are 1 to 2 year parameters. These are not 6 month parameters. So the 6 month parameters, what you're looking for or at least what we're looking for working with our thought leaders is there's about 6 or 7 different measures of physical, physical function, cognitive function, a variety of different things, well established measures. And what you want to see is stability across those measures or no decline. Obviously, if you have improvement, that's fantastic, but it's way too early quite frankly to even assess an improvement. But if you're able to show stability and no decline in function, that is the win because these progressive patients will decline in function. So that's really what we're looking for is can you show stability or no decline in function across those various parameters across multiple parameters in a single patient. And again, I mean, this study is really there to determine a Phase 2 dose that we'll use, by the way, in our Phase 1b. And that's mainly based on safety and tolerability. But of course, all these efficacy parameters will inform of choice of the dose for the next portion of the study. May I ask one follow-up and that is in the progressive patients, will all have had or will they still be on and I'm sorry I did not look for the exclusion criteria, will they have had or still be on ocrelizumab? Thank you. Yes. They would all need to wash out of ocrelizumab before they enter the study. And ocrelizumab or any other disease modifying agent would have to be washed out before they enter the study. Thanks, Rachael. Thank you, Crystal. Sure. Thank you. And our next question comes from Yigal Nochomovitz from Citi. Your line is now open. Hi, thanks for taking the question. This is Samantha on for Yigal. I wanted to build on an earlier question on your next gen CAR T for mesothelin, specifically in respect to your dominant negative PD-one. Can you just go through all the advantages you see with including this into your CAR T versus just dosing with a PD-one? Because the MSK data suggests that you're already getting a really high response rate with pembrolizumab. I'm just curious on your thoughts there. No, that's a great question. Thank you. Chris, do you want to start? And then I'll give some feedback as well there. Sure. So, the inclusion of the dominant negative for PD-one in the preclinical models had additional anti tumor efficacy compared to the preclinical combination of CAR T cells plus an antibody based checkpoint inhibitor. Specifically, a higher proportion of the animal study had complete response of their tumor. And in addition, there was great durability. So we see a couple of important advantages in that way. In addition, of course, there's a factor of patient convenience as the combination being present in the T cell itself and able to essentially carry that checkpoint inhibitory function into the tumor in a manner like a Trojan horse allows them to then have a more convenient treatment potentially as development proceeds. And I think the belief there is that to have the joint approach on the construct will really allow a more physiological way of targeting PD-one there. And that is, as Chris has said, backed up by some animal data. But of course, we need now to go into patients and to prove that this is a better approach than combining with regular administration of PD-one blocker. Thanks for that additional detail. And then in the MSK data at ASCO, 11 out of those 16 patients were PD-one negative, but you still saw really great response rates in that population. I'm just curious whether you think expressing PD L1 is important for this therapy and do you plan to screen in your potential to plan Phase 1 for in 2020? So there was no correlation with PD L1 expression or status on the outcome in the data presented by our MSK collaborators, Doctor. Eddy Smiley and colleagues at ASCO. One thing to bear in mind is that when T cells enter the tumor environment, there's a release of cytokines that will dynamically change the expression of PD L1 and that maybe why it's so important to have the combination present. So I think the baseline PD L1 expression is generally low in mesothelioma, but that may not be the most important factor in a combination therapy that works through an immune mechanism because the cytokines would be expected to dynamically change that axis. And again, having the DNR here could be an advantage because then in situ, that's what is really important about the activity of the T cells when they have harmed the tumor there is the in situ immunosuppressive environment that is led by the PD L1 expression there. And having that through the DNR makes a lot of sense. Great. Thanks for taking our question. Thank you. And our next question comes from Salveen Richter from Goldman Sachs. Your line is now open. Yes. Hi. Thank you for taking the question. It's Mariana Brightman for Salveen. I have a couple. One of them, following up on the mesothelin sort of rationale for the changes, I also wanted to get a better sense for the timeline. And I also was trying to understand what are the manufacturing stages that process is in? What are the vectors have been made and how far along are we basically in preparation for the 2020 study? Sorry, when you say the change of the timeline for the No, no, just to understand the timeline, what is Okay, sorry. Okay. No, no. Sorry for that. So, we're working with our collaborators at MSK to be able to be ready for the IND and this is progressing very well. Our guidance has been that we will be I mean, our collaborators will be filing an IND in 2020 on this next generation CAR T, and we are very confident in this guidance. Meanwhile, as you know, we are also progressing in supporting the 1st generation study that is continuing. There is an important medical need. And as you can see, the efficacy and safety results are encouraging there. And we believe we are learning a lot from that study that and that learnings could be applied to our first study with the next generation mesoCAR T there. So time lines are in line with the guidance and things are progressing very well there for 2020. And manufacturing at this stage is to be done initially at MSK and will be transferred at our ATOM unit in due time. Got it. Thank you. Thank you. And our next question comes from Maury Raycroft from Jefferies. Your line is now open. Hi. Thank you for taking my questions. This is David on for Maury. First question is regarding tab cel. Just can you share with us any updates on the expanded access program, such as updates on the number of patients included, type of patients enrolling? And if you will report any new data from this program? Thank you for your question. So we are not giving any number of patients at this stage, but the program is really recruiting a lot of patients that either cannot participate to the study itself. The Phase III studies cannot be enrolled in the Phase III studies or add different type of patients there. So we're very pleased with the enrollment in that program and we will communicate at future congresses new data on this program. Got it. That's very helpful. And the second question is for the TAPCO, can you talk about the status of your nasopharyngeal carcinoma trial? How is enrollment currently going? And what's the sort of plan for the disclosure? Thank you for your question. A. G, do you want to answer that one? Sure. So the NPC studies as you know is ongoing. We're in the first phase of the program where we're looking to enroll anywhere between 12 24 patients in the study. As you know, it's the first time we've ever really combined cell therapy with PD-one inhibition from when I say cell therapy, the first time we've combined tab cel with PD-one inhibitor. So the major focus for us here is going to be really assessing the safety of the combination initially. From a timing of data, we're not expecting to present data this year on that program just yet. Got it. That's very helpful. And then last question is on the anti mesothelin CAR T. Can you just share with us any preliminary thoughts around your potential trial design for the CAR T program in 2020? So again, the IND is planned for filing in 2020. We are not right now giving any details on the protocol because we are discussing it right now. And we will give details on that protocol in due time. Again, that is important that we will take into account all the learnings from the 1st generation and what we're doing there. I think that's an important aspect to optimize the IND and the 1st in human study for this next generation CAR T. We're very confident that we will be able to start that in 2020 as planned with an appropriate protocol that will really allow us to have proof of concept of the clinical efficacy and safety of this next generation CAR T as rapidly as possible. Got it. Thank you for taking my questions. Thank you. And our last question comes from Ben Burnett from Stifel. And Pascal, great to see you on board and congrats. Two questions for me. Just one first, just to clarify on ATA188. What cohorts or dose levels specifically will we see efficacy data for Actharim's? And then also have patients so far in the Phase 1 progressed or made it to the point where they can enroll in the open label extension? And if they have, I guess, what's sort of been the enrollment rate or retention rate into that study? Thank you, Ben for your question, AG. Sure. And I may ask for a clarification on Part 2 of the question. So in terms of the cohorts, we'll be presenting data on 2 cohorts out to the first two cohorts out to about 6 months worth of data. We may have a little bit more on one of the initial cohorts, but again it's really just a timing issue in terms of how long the patients have been in study at this point. In terms of the enrollment into extension, I apologize, but can you clarify that because for what we have right now just as a plan is as we finish this 4th dosing cohort and we're close to finishing the 4th cohort now, We'll make kind of a database decision as to what the dosing will be for the randomized portion of this study. And is that what you're talking about as extension? Well, I'm referring to a study schema that you guys presented at EAN, wherein it looks like cohorts 1, 2, 3 and 4 have the opportunity to go into an open label extension after 1 year of treatment. I guess I was asking if anyone's made it to that point yet and what the sort of retention rates been into that section? That's okay. Now I apologize. Thank you for the clarity. Yes, so we do have a few patients in from the first cohort that have gotten out past a year and are going into the extension. I'm never going to be able to comment on percentages or anything like that because it's a little bit too early. But we do have patients who have gotten out to that time point. Okay. Okay, understood. Thank you for that. And then just one last one on tab cel and PTLD. I guess can you just talk in a little more detail about the logistics of getting patients enrolled into this study? I guess really why has it been so challenging to forecast enrollment rates? And I guess what gives you the confidence now that enrollment can be accurately forecast going forward? Sure. It's a great question. So what are the probably the prime difficulty, you know this is an ultra rare disease. So clearly, ultra rare presents challenges. And this is a different challenge in some of the other ultra rare diseases out there, because this is one where the patients really do come up in randomly. There's not major centers of excellence where you're going to have a high concentration of patients. That's step 1. Step 2 is the timing because when you look at this, you're really looking at patients catching them right as they fail therapy. Now normally that's not that big of a problem, but here these patients progress so rapidly to death that there's a short window of opportunity to really help them. So you still catching them in exactly that window is part of is a second challenge. We've done really well actually we've in terms of the operational efficiencies we've created to make sure we can catch these patients. That act has gone extremely well and we've gotten a lot better over the course of the study in achieving that. So that's what gives us a bit more confidence that we'll be able to enroll correctly or at least on the pace that we're targeting. The third thing just to keep in mind and I'm going to roll this back into the EAP program a little bit. Part of the challenges that you have is, as I mentioned, these patients kind of come up everywhere. And when we find a patient who, for example, is not at a clinical trial site, we'll actually move them over to wherever the clinical trial site is irrespective where that is in the country. But you also have to remember that these patients are often so sick that you can't actually transfer them or they have a medical they're not they're able to be transferred medically but they have a specific issue that actually prevents the transfer process. And in those cases, those are patients that get on to our expanded access program, which is what Pascal has alluded to where we actually have a fair number of patients on our expanded access program, both for PTLD and for other EBV conditions. But those are the major factors into why I think the enrollment has been a little bit difficult to work through. But since we have focused in our existing centers, we've created these operational efficiencies to make sure that that timing component, which is really critical, is not as much of a factor as it has been in the past. And to build on that, I think our confidence in the guidance is linked to the fact that we've learned so much onto the study that now we are confident that we can deliver what we said regarding the initiation of BLA submission in the second half of twenty twenty. Also to take have in mind that in a commercial setting, it will be vastly different there because we'll have the product available within 3 days to any site, any physician that is in need of that product for his patients across the country. And in the U. S, which is a very attractive market for this type of retroviral disease, that means that this possibility to treat the patient extremely rapidly offered by our TAV cell as an allogeneic T cell that is available within 3 days is going to be immensely useful for patients and physicians. Okay, great. Thanks so much for the additional color there and congrats again, Pascal. Thank you. Thank you very much, Julien. Thank you. And I'm not showing any further questions at this time. I would now like to turn the call back to Pascal Toussaint, President and CEO for any further remarks. Thank you very much and thank you everybody for having joined that call. I want to thank really you for taking the time to join us today. Look forward to providing updates for the remainder of the year on a regular basis as we continue to advance our position as a leader in the up the shelf allogeneic T cell immunotherapy. Thank you very much. Ladies and gentlemen, thank you for your participation in today's conference. This does conclude today's program. You may all disconnect. Everyone have a great day.