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 listen-only mode. Later, we will conduct a question and answer session. Instruction will follow at that time. If anyone should require assistance at any time, please press star then zero on your touch tone telephone. I would now like to turn the conference over to your host, Dr. John Craighead, Vice President, Investor Relations and Corporate Communications. You may begin. Thank you, operator. Welcome to the Atara second quarter 2019 financial results and corporate update conference call. Earlier this morning, we issued a press release providing an overview of the company's second quarter 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 atarabio.com. I'm joined on the call today by Dr. Pascal Touchon, President and Chief Executive Officer, Utpal Koppikar, Chief Financial Officer, Dr. Chris Haqq, Chief Scientific Officer, and Dr. AJ Joshi, Chief Medical Officer. We'll begin with prepared comments from Pascal, 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. I would like to turn the call over to Atara's President and Chief Executive Officer, Pascal Touchon. 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 served as Global Head Cell & Gene 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 financial 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 Cellectis 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. Having worked over the last five years in the field of autologous CAR-T, as well as first-generation gene-edited allogeneic CAR-T, I believe cell therapy is the 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. Our allogeneic T-cell therapies may be immunoprivileged. They're obtained from healthy donors and do not require HLA edits, hence maintaining proliferation and persistence advantages. As they are matched for each patient from our 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 Epstein-Barr virus, or EBV, specific platform can lead to therapies directed at EBV-associated diseases like tab-cel and ATA188, as well as allogeneic CAR-T therapies. Our platform is already in clinical development for EBV-associated post-transplant lymphoproliferative 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 ATA2271, 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. 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 relapse refractory EBV positive PTLD during the second half of 2020. 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 two ongoing tab-cel clinical studies into a single study called ALLELE. 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. 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 three to 12 months in the case of SOT. In NCT, survival after rituximab failure is about one month. In the U.S., we estimate that there are several hundred patients with EBV-positive PTLD who have failed rituximab with or without chemo. This is a typical ultra-rare 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, tab-cel has demonstrated in both phase II and EAP studies that it has a high and durable treatment effect, with objective response rates between 50% and 83%, and overall survival in responders at two years of over 80% in both NCT 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 two-hour post-administration monitoring in clinical trials. Additionally, our off-the-shelf T-cell order, match, and supply management system is designed to deliver the treatment within three days. Beyond the significant business case in PTLD, we are excited about the potential of tab-cel as an ultra-rare disease pipeline in a product. Tab-cel is in ongoing phase II clinical development for patients with platinum pre-treated 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 third tab-cel opportunity is based on a multi-cohort Phase II study that we expect to start in the second half of 2020. We plan to enroll patients having all the 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 our innovative platform in developing the first 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 for ATA188 at the fifth 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 fourth and final planned 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 patients, as well as immunocompromised PTLD patients. Although designed to evaluate safety and tolerability in order to determine a recommended phase II 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 ECTRIMS in September, as well as additional safety results. On the basis of the phase I-A data, we plan to proceed into the randomized, placebo-controlled portion of the study. In parallel, we plan to initiate a randomized phase II study of ATA190, an autologous version of ATA188, during the second half of this year to compare the efficacy and safety profile of these two 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 two presentations by our MSK collaborators on the phase I clinical study with a mesothelin-targeted CAR-T immunotherapy in patients with advanced mesothelioma. Mesothelin 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 mesothelioma. In the latest ASCO presentation, a subset of 16 patients with malignant mesothelioma followed for a minimum of three months and receiving MSK MesoCAR T together with anti-PD-1 and lymphodepleting chemotherapy showed a 12-month overall survival rate of 80% and an objective response rate of 63%. We view this data as highly encouraging and have prioritized our mesothelin-targeted next generation CAR-T program, ATA2271, 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 million for the issuance of 6.9 million shares of common stock and 2.9 million prefunded warrants. These successful offerings strengthen our financial positions and firms plan operation into 2021 for key milestones next year, including initiating the tab-cel BLA submission and next generation mesothelin 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 you. Ladies and gentlemen, if you have a question at this time, please press star then one on your touch-tone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. To prevent any background noise, we ask that you mute your line once your question has been stated. As a reminder, ladies and gentlemen, that is star then one for questions. Our first question comes from Anupam Rama from JP Morgan. Your line is now open. Good morning, all. This is Tessa filling in for Anupam this morning. Thank you for taking our questions, and it's very nice to meet you, Pascal. My question is on MS. With first efficacy data for ATA188 coming at ECTRIMS 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 I 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. I will ask AJ Joshi to start answering that question. Thank you, Pascal. Just to put things in perspective here, this is, of course, a study that is focusing on the progressive MS population. Really, the focus in progressive MS is to delay deterioration. That's really the end goal. In order to assess that particular parameter, most parameters actually you need about one to two years of assessment to really prove anything. Our challenge in setting this study up was: How do we get an earlier read than a couple of years? As you know, these data are going to be around six months data on a couple of cohorts of patients. We worked with thought leaders to essentially define multiple parameters that are well-defined, clinically meaningful, and 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. I should step back for just a second. 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's a real signal there at an earlier time point than that one to two years that I was talking about. Success for us here would look like movement across multiple parameters at the time points that we describe when the data are presented. Just to add on that, ECTRIMS is an important step in building up evidence in terms of safety and efficacy for ATA188. We can move to, at a later stage when we have completed this phase I-A study, into phase I-B. We expect to present initial efficacy results from the lower dose cohort, as well as additional safety results from the higher dose cohort. The fourth and final planned dose cohort is almost fully enrolled, but we do not expect to have efficacy data available at the time on the fourth cohort at ECTRIMS in September. 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. 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? If you have any additional details on what you're doing besides that to help enrollment? Thank you for your question. I think AJ, you might want to start answering that question. Sure. In terms of speed of getting sites up and running, for PTLD, you're really looking at larger scale academic centers. 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. We're starting to really see the benefits of getting those sites coming in. Because, as you know, academic centers often takes anywhere between six and nine months to really get up and running. Again, we've done a lot of that lead in already. We do expect to open up several additional sites in the U.S. later this year. In addition, we are opening up additional geographies because we recently got a no objection letter from Health Canada. We'll be opening up our first Canadian site later this year. 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. This has been leveraging a variety of resources, including medical science liaisons and other activities that I implemented in previous lives in ultra-rare indications. Multiple activities from ultra-rare 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. 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. 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 rapidly progressing, where sometimes the patient cannot wait for the administrative burden of being recruited in the study. 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. I think there are about 12 clinical trials right now in that space. 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. Other questions? Thank you. 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. 1 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, they will have immune systems. When you're looking at efficacy, 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 it to PTLD, that was an immune system knockout patient. 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 ATA188 versus ATA190. If there's any theoretical risk here of one 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 188 because it's not perfectly HLA matched. Then the last question is just, can you provide more interim details on the tab-cel program? How many patients do you need for the interim, and what would the ORR hurdle be? Thank you. Thank you very much. AJ, do you want to start? Sure. In terms of the persistence question. We have actually experience with EBV-directed T cells, EBV-targeted T cells in an immunocompetent population with the nasopharyngeal carcinoma program. As you know, in the phase I studies at MSK, we had about a 20% response rate in essentially an immunocompetent population. 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. From that perspective, I think there's relative confidence that we should have enough persistence to get an efficacy signal and maintain efficacy appropriately. 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 II 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. 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. On the auto and allo program in MS, AJ? I apologize, would you mind repeating the specific question on auto versus allo? Oh, no, I think you answered that question. Great. I think the last question was just around the interim details. How many patients and what the ORR hurdle would be? Sure. As you might imagine, 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. 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% to meet the statistical hurdle. As you might imagine, any interim analysis that we do would have to have a higher ORR statistical hurdle to meet the requirement. Okay, great. Thanks so much, guys. Thank you. Thank you. Our next question comes from Matt Phillips from William Blair. Your line is now open. Hi, thanks for taking my questions. 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. I'm wondering how many of those can enroll both solid transplant and bone marrow transplant patients as opposed to maybe just one or the other? When it was two separate studies, there was not, I mean, in a lot of them, some of them were overlapping, some of them weren't. 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, or will we get some info? I think some disclosure on how it's going would be important given how long it's taken. Thank you for your questions and for your welcome remark there. On the number of sites, we say 34 that are unique sites, but of course, some of them are doing both. We have about 23 sites for phase I and 27 sites for phase II that are open for enrollment right now. I think as we said, we are going to increase this number of sites in the U.S. and also with the recent good news from Canada, open by the end of the year, Canadian site, before moving to Europe following the CTA submission there. In terms of 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 of the 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. Yes, thank you. Just to add on that, just to be clear, we plan to communicate on our guidance. When we say we will initiate BLA submission in second half of 2020, we plan to communicate on that initiation at that time. Thank you. Our next question comes from Phil Naidu 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 need agreement between the company and the European regulators? Is it endpoints, enrollment criteria? Where is the debate? As you know, we've adapted, amended our protocol for SOT, and we have merged two studies together, the SOT and the HCT study in one study with two cohorts. That's something that has been based on our discussion and constructive dialogue with the FDA. We need to discuss with the EMA throughout these changes and see how do they react to that. 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. Of course, you may benefit for an accelerated review then. 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. It's really around this change in the protocol that is linked with our discussion with the FDA that now we need to discuss with the EMA. Do you have some sense when your discussions with the EMA will conclude? 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. Next question on the next generation CAR-T. Can you remind us what is the difference between your autologous ATA2271 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. 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-1 dominant negative. We'll be using the identical binding domain as has been used in the presentations given at AACR and ASCO. 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 the 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. We have that scFv, that's something that we are learning from the first generation CAR T development of our collaborators at MSK. That same scFv 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. Of course, we have added the PD-1 DNR to have really a more physiological way of addressing the need to target PD-1 and make sure that we have enough activity of the cells once they have penetrated into the tumor. Perfect. My last question is on the earlier pipeline. Is there any update on ATA3219, the anti-CD19 CAR-T or ATA2431, the 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 three targets there. That's with Moffitt, of course. For the CD19, which is an Atara development, this development is progressing well. As you know, objective here is really in a very well-known type of CAR-T target to be able to show efficacy and safety that will allow to prove the concept of allogeneic CAR-T based on EBV-specific cells. Both programs are progressing. We don't have any special comment to make on a specific type of achievements there, but they are progressing very well. Great. Thanks for taking my questions. Thank you. 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 ATA188 in MS, in ECTRIMS. There are three questions. Number one is, you stated in the release that you're looking at progressive forms of MS, yet in clinical trials, it's actually both relapse permitting and also progressive. I'm curious what we get at ECTRIMS directly. That's number one. Number two is, while you clearly won't have any MR, or there will not have been enough time for patients who 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. 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. This is AJ. Let me start with the third question. Apologies if there was any miscommunication or misunderstanding. There's 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 treated patients with 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. There's very good proof that these T cells that we create virally targeted access the CNS compartment well and exert their function. That was the proof source for why we believe all of these cells are getting in to exert function for MS. It's not really PTLD. Hope that answers question three. It does, AJ, and thank you. My apologies for misunderstanding. No worries. And then- Going back to the first question on progressive versus relapse 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. Also it's really a progressive MS population that really doesn't have a lot of inflammatory disease. When you mention MRIs, you're right. There's a lot of times you can get relatively early reads in active disease by tracking MRI status. This is not active disease. We really want to focus in on the progressive component, which is where really most other therapies have failed. We think that's the differentiator here. For us, 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 timed 25-foot walk tests and whole brain volume reduction. Again, those are one to two-year parameters. These are not six-month parameters. The six-month parameters, what you're looking for, or at least what we're looking for working with our thought leaders, is there's about six or seven different measures of physical function, cognitive function, a variety of different things, well-established measures. 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. If you're able to show stability and no decline in function, that is the win, because these progressive patients will decline in function. 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. Again, I mean, this study is really there to determine a phase II dose that we'll use, by the way, in our phase I-B, and that's mainly based on safety and tolerability. 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. They would all need to wash out of ocrelizumab before they enter the study. Ocrelizumab or any other disease modifying agent would have to be washed out before they enter the study. Thank you, AJ. Thank you, Christophe. Sure. Thank you. 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 mesothelioma, specifically in respect to your dominant negative PD-1. Can you just go through all the advantages you see with including this into your CAR-T versus just dosing with a PD-1? 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 then. Sure. The inclusion of the dominant negative for PD-1 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 studied had complete response of their tumor. In addition, there was great durability. 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. Yeah, I think that the belief there is that to have the joint approach on the construct will really allow a more physiological way of targeting PD-1 there. That is, as Chris has said, backed up by some animal data. Of course, we need now to go into patients and to prove that this is a better approach than combining with regular administration of a PD-1 blocker. Thanks for that additional detail. In the MSK data at ASCO, 11 out of those 16 patients were PD-1 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 I in 2020? There was no correlation with PD-L1 expression or status on the outcome in the data presented by our MSK collaborators, Dr. Adusumilli 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 may be why it's so important to have the combination present. 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. 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 home to the tumor there, is the in situ immunosuppressive environment that is laid by the PD-L1 expression there. Having that for the DNR makes a lot of sense. Great. Thanks for taking our question. Thank you. Our next question comes from Salveen Richter from Goldman Sachs. Your line is now open. Yes, hi. Thank you for taking the question. Marianna Brighton 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 that process is in. Whether 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 miso-? No, just to understand the timeline. What is- Okay. Sorry. What- Okay. No, sorry for that. We 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 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 first generation study that is continuing. There is an important medical need, and as you can see, the efficacy and safety results are encouraging there. We believe we are learning a lot from that study, and that learnings could be applied to our first study with the next generation mesothelin CAR-T there. Timelines are in line with the guidance, and things are progressing very well there for 2020. Manufacturing, at this stage, is to be done initially at MSK and will be transferred at our Atara unit in due time. Got it. Thank you. Thank you. 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 the tab-cel. Can you share with us any updates on the expanded access program? Such as updates on the number of patients included, how about patients enrolling, and if you will report any new data from this program. Thank you for your question. 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 are different type of patients there. We are 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. The second question is, for the tab-cel, can you talk about the status of your nasopharyngeal carcinoma trial? How is the enrollment currently going, and what's the sort of plan for data disclosure? Thank you for your question. A.J., do you want to answer that one? Sure. Yeah, the NPC study, as you know, is ongoing. We're in the first phase of the program, where we're looking to enroll anywhere between 12 and 24 patients in the study. As you know, it's the first time we've ever really combined cell therapy with PD-1 inhibition. When I say cell therapy, the first time we've combined tab-cel with PD-1 inhibitor. 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. Oh, got it. That's very helpful. The 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? 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 first generation and what we're doing there. I think that's an important aspect to optimize the IND and the first-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. Our last question comes from Benjamin Burnett from Stifel. Your line is now open. Hey, great. Thanks so much for taking my questions. Pascal, great to see you on board, and congrats. Two questions for me. One first, just to clarify on ATA188. What cohorts or dose levels specifically will we see efficacy data for at ECTRIMS? Have patients so far in the phase I progressed or made it to the point where they can enroll in the open label extension? If they have, I guess, what's sort of been your enrollment rate or retention rate into that study? Thank you, Ben, for your question. AJ? Sure. I may ask for clarification on part two of the question. In terms of the cohort, we'll be presenting data on the first 2 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. Can you clarify that? For what we have right now, just as a plan is, as we finish this 4th dosing cohort, 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. Is that what you're talking about as extension? Well, referring to a study schema that you guys presented at EAN, where it looks like cohorts 1, 2, 3, and 4 have the opportunity to go into an open label extension after one year of treatment. I guess I was asking if anyone's made it to that point yet and what the sort of retention rate's been into that section. Okay. Now, I apologize. Thank you for the clarity. Yeah. 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 not really going to be able to comment on percentages or anything like that because it's a little bit too early. We do have patients who have gotten out to that time point. Okay. Understood. Thank you for that. 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. 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 one. Step two is the timing, because when you look at this, you're really looking at patients, catching them right as they fail therapy. 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. Catching them at exactly that window is a second challenge. We've done really well, actually. In terms of the operational efficiencies we've created to make sure we can catch these patients, that actually has gone extremely well, and we've gotten a lot better over the course of the study in achieving that. 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, 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. 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 of where that is in the country. You also have to remember that these patients are often so sick that you can't actually transfer them, or they're able to be transferred medically, but they have a specific issue that actually prevents the transfer process. In those cases, those are patients that get onto 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. Those are the major factors into why I think the enrollment has been a little bit difficult to work through. Since we have focused in on 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. To build on that, I think our confidence in the guidance is linked with the fact that we've learned so much onto the study, that now we're confident that we can deliver what we said regarding the initiation of a BLA submission in second half of 2020. To have in mind that in a commercial setting, it'll be vastly different there, because we'll have the product available within three days to any site, any physician that is in need of that product for his patients across the country. In the U.S., which is a very attractive market for this type of a driver disease, that means that this possibility to treat the patient extremely rapidly offered by our tab-cel as an allogeneic T-cell that is available within three days is going to be immensely useful for patients and physicians. Okay, great. Thanks so much for the additional color there. Congrats again, Pascal. Thank you. Thank you very much, Ben. Thank you. I'm not showing any further questions at this time. I would now like to turn the call back to Pascal Touchon, 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. We 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 off-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.