Atara Biotherapeutics, Inc. (ATRA) on Q1 2021 Results - Earnings Call Transcript
Operator: Good afternoon, everyone. Thank you for standing by and welcome to the Atara Biotherapeutics First Quarter 2021 Financial Results Conference Call. Please be advised that today's call is being recorded. I would now like to hand the call over to Eric Hyllengren, Vice President of Investor Relations and Finance at Atara Biotherapeutics. Please go ahead, sir.
Eric Hyllengren: Thank you, Rob. Good afternoon, everyone, and welcome to Atara's First Quarter 2021 Results Conference Call. Earlier today, we issued a press release announcing our first quarter financial results and operational progress. This press release and an updated investor presentation are available in the Investors and Media section at atarabio.com. On today's call, members from the Atara executive team will provide an update on our financial results and operational progress, and also review our upcoming key milestones and objectives. Joining me on today's call are Dr. Pascal Touchon, President and Chief Executive Officer; Dr. Jakob Dupont, Executive Vice President and Global Head of Research and Development; Utpal Koppikar, Chief Financial Officer; Joe Newell, Chief Operations Officer; Dr. AJ Joshi, Chief Medical Officer; and Dr. Kristin Yarema, Chief Commercial Officer. We will begin with prepared comments from Pascal and Jakob, then open up the call for your questions. We would like to remind listeners that during the call, the company's management will be making forward-looking statements. Actual results could differ materially from those stated or implied by our forward-looking statements due to risks and uncertainties associated with the company's business. These forward-looking statements are qualified in their entirety by the cautionary statements contained in today's press release and the company's SEC filings. These statements are made as of today's date, and the company undertakes no obligation to update these statements. Now I'd like to turn the call over to Pascal. Pascal?
Pascal Touchon: Thank you, Eric, and thank you all for joining us this afternoon. We are off to a strong start in 2021, making progress on all three of our strategic priorities; tab-cel, ATA188 in multiple sclerosis, and our next-generation allogeneic CAR T programs. We are moving ahead to deliver on our key milestones this year, including the expected tab-cel BLA and MAA filings, progress on the ATA188 program, especially presentation of new clinical and translational data from our Phase 1 open-label extension study, and first clinical data on our mesothelin CAR T program in advanced mesothelioma. For tab-cel, we are in active discussions with the FDA on the content of CMC Module 3, including methodologies and data to assess comparability between the product used in the pivotal clinical study and the intended commercial product. Supported by our Breakthrough Therapy designation, we have been having regular dialogue since January with the FDA on the CMC Module 3. And most recently, a teleconference last Friday, where we discussed key aspects of our comparability data package. We believe that we have provided the FDA a robust data package to demonstrate comparability between various process versions of tab-cel, and we are encouraged by the ongoing interactions as we work towards aligning with the FDA.
Jakob Dupont: Thank you, Pascal. As Pascal described, we've made steady progress across all three of our strategic priorities in the first quarter. For tab-cel, we are in active discussions with the FDA and are aligned on key aspects of comparability with regulators. We are the first allogeneic T-cell therapy company to be ready to submit a BLA for FDA approval. The discussions we are having with FDA are part of our BTD status prior to BLA submission and may set precedents for other allogeneic products that follow. At this time, we are focused on the CMC Module 3 with the FDA and we believe that we have provided a robust data package to determine comparability between various process versions of tab-cel and are encouraged by the ongoing interactions. We expect to align on comparability and then we plan to complete our BLA submission for PTLD in the third quarter of this year. Our confidence is reinforced by the fact that tab-cel is truly remarkable for an investigational product being developed for an ultra-rare disease. In that, it already has many years of clinical experience with nearly 300 patients treated with life-threatening EBV positive diseases in clinical trials, as well as expanded access in single patient use settings, including 150 patients with EBV positive PTLD. This clinical experience shows the tab-cel's efficacy and safety profile in PTLD patients is consistent from both an efficacy and safety perspective, irrespective of product version and across studies, including the pivotal ALLELE study interim analysis data. Additionally, we are presenting combined long-term overall survival data from clinical studies of tab-cel at two medical congresses. Data from three clinical studies of tab-cel demonstrates that patients with EBV positive PTLD, following either HCT or SOT that is relapsed refractory to initial treatment have over 80% two-year survival whether they achieved a complete or a partial response. For perspective, these patients with EBV positive PTLD after HCT or SOT have a median survival of only two to three months in the second line and beyond treatment setting without tab-cel treatment. These data suggest the potential transformative impact for these patients in great need, and that tab-cel may provide an effective treatment options marked by long-term overall survival regardless of partial or complete response. Of note, the British Society of Hematology just released updated guidelines for the management of EBV positive PTLD. These guidelines specifically recommend the use of EBV positive or EBV specific CTO immunotherapy for relapsed refractory PTLD including CNS PTLD where available. And tab-cel data were particularly referenced among several datasets. These guideline recommendations are similar to the NCCN guidelines for non-Hodgkin's lymphoma that also recommend EBV specific CTO therapy like tab-cel for relapsed refractory EBV positive PTLD.
Operator: Thank you. Our first question today will be coming from the line of John Newman with Canaccord Genuity. Please proceed with your questions.
John Newman: Hi, guys, thanks for taking the questions, and congratulations on the continued progress. Question I have is regarding the tab-cel filing. Pascal, if I can remember correctly, last year when you and Atara disclosed the data on tab-cel. I think you had also mentioned that you had come to an agreement or understanding with the FDA in terms of the number of patients that they would like to see for the filing. I'm just curious if that was the case. The reason I'm asking is because it's always seemed to me like the discussion you're having regarding the previous data generated at Sloan Kettering and the data that you've generated is more around the analysis rather than the amount of data. So I just wondered if you could discuss that. Thank you.
Pascal Touchon: Thank you, John, for your question. Jakob, do you want to start answering that? And I'll make another comment after that.
Jakob Dupont: Yes. So we do believe that the guidance still holds that the number of patients that we've enrolled in ALLELE is sufficient for the BLA filing. Now what we've been working on, which Pascal reported on today is that we now know more about the durability of response of these patients and that data is looking good. Now, of course, we still are working on this issue of comparability, which will help us to get to the point of initiating the BLA. And it will also help us to position the historical data relative to the pivotal data from the ALLELE study, where we either present the historical data in parallel on the BLA filing or in the field analysis. Pascal?
Pascal Touchon: Yes. And just to clarify, as we said in the past, John that we are planning a data cut in Q2 with new data available in Q3 to be able to complete the Clinical Module 5 for the BLA submission. And what we're doing meanwhile is really to work on the CMC Model 3. Does it answer your question?
John Newman: Yes. Thank you.
Operator: Thank you. Our next question comes from the line of Salim Syed with Mizuho. Please proceed with your questions
Salim Syed: Great. Good afternoon, guys. Thanks for all the color and congrats on all the progress. A couple from me on ATA188, if I can. The first, I don't know, maybe this for AJ or Jakob perhaps, or Pascal. As we approach the interim data in the first half of 2022, just curious how you guys are thinking about the overall program here for ATA188. What do you need to see on that interim that would make you confident that you can convert this to a registrational study and apply for approval just on this one trial. And then the second question is more just on your discussions with the FDA. If I recall, on the last call, you had mentioned in the coming months, you'd have some discussions on whether SPMS and PPMS would be treated as one population or two. Have you had those discussions or is there any update you can provide there? Thanks so much.
Pascal Touchon: Thank you, Salim, for your two questions. So first question, AJ.
AJ Joshi: Sure. And then to some extent, Salim, they're a little bit interrelated. When you talk about the interim analysis, there's two elements of it. Our feel for what would make this potential registrational trial starts with alignment with FDA on that patient population we talked about earlier. So whether they're going – whether they want us to look at this as two separate progressive MS populations, or as we've articulated a single non-active progressive MS population. Depending on how that answer comes out, then we will then take a look at the interim analysis data. And there, when we see the data, and again, you know, we have a specific SAP that take – that's kind of going to govern how we approach this. When we see the data, we're going to look to potentially adjust the sample size, to make sure we have the best chance of hitting the right power for the study. And now if the FDA, for example, has given us good alignment around that patient population, we might have a small adjustment in sample size to kind of make this a robust Phase 2 study or maybe a larger adjustment in sample size if we think that there's an opportunity to essentially turn this into one of two pivotals. Whether this could be the only pivotal, I think that's a – that would be a great kind of grand slam, but I think that would really be dependent on lots of conversations with FDA. I think our base case is strong Phase 2, good potential to turn this into a one of two pivotal programs, depending on those discussions with FDA and the interim analysis. And then, the last piece that you mentioned would really be amazing, but I think that's not really something we anticipate as a single study just yet.
Pascal Touchon: Yes. And maybe to also answer your second question a bit more in detail, what we've done recently, we had very nice interaction with thought leaders, medical expert of MS. But in fact, I've worked with different kind of consensus position on the patients with SPMS and PPMS there. And these experts are all clear that this is the same disease, and this is the same evolution of these patients there, from the pathophysiological aspect there. So we are reinforcing our belief with this expert position that has been communicated publicly. And now we are planning an interaction with the FDA, leveraging these expert positions to discuss with them whether it could be one or two population from a pivotal point of view story. It doesn't change anything on the Phase 2. It’s just, as AJ just say, if we want to leverage this Phase 2 importantly transforming this into a Phase 3 pivotal study, we need to have this alignment about – is that one population or is it two population in that study? But we are very encouraged by the expert view on this particular question. Does it answer your question?
Salim Syed: Yes, it does. Thanks so much, guys. Appreciate it.
Pascal Touchon: Thank you, Salim.
Operator: Our next question is coming from the line of Jonathan Miller of Evercore ISI. Please proceed with your questions.
Jonathan Miller: Hey, guys. Thanks so much for taking the questions. Just a couple of quick ones, I guess. Just to clarify, it seems like the tab-cel BLA, still expected 3Q. Obviously, you're having all these interactions with the agency, but it feels like there's still some Ts to cross. When do you know for sure that you'll be able to file on time? Or is that the sort of thing that we're not actually going to know until the filing comes in 3Q? Secondly, the tab-cel multi-cohort study is opening sites, but are you enrolling and dosing it? What's the time line look like for actually getting patients into those cohorts? And do you have a sense on when we could hope to see the initial data from those most important first couple of cohorts? And then just switching gears a little bit on mesothelin CAR data coming in Q4. Is it fair to expect enough patients there to get a sense for ORR? Or is this going to be really a very small cohort and we shouldn't be expecting to get a robust ORR from it? Will we get persistence data at that point to complement the AACR presentation that you were talking about? What can we expect out of that initial mesothelin presentation? Thanks.
Pascal Touchon: Okay. Thank you, Jon, for your three questions. Let's start with the first one. Jakob, do you want to address the first one about the – when we will know exactly whether we can finally complete the BLA?
Jakob Dupont: Yes, absolutely. So, Jon, thank you so much for your question. So because of our BTD status, we benefit from a number of active interactions with the FDA to speak about this comparability issue. So we've had a number of type B meetings and informal calls with the FDA over the last several months to discuss comparability and other topics related to that CMC Module 3. And as we've described, these are progressing well. And the active dialogue with the FDA has to be taken into context because we are bringing forward the first allogeneic T cell therapy for a submission for an FDA approval. So we think with these discussions, we're making good progress on comparability. And as Pascal mentioned, we’re also working towards an additional data cut to complete that Module 5. So as we mentioned, we are still moving towards that completion of the BLA filing by Q3 of this year, obviously with these active engagements with the agency on comparability.
Pascal Touchon: Yes. So just to add on that, I think we are really according to our plan, we’re working on these different aspects, I would say, in parallel, both the clinical and the CMC part. And so we are working ahead to move into that BLA filing in Q3, moving ahead with different discussions with the FDA. We'll continue to transparently communicate with our investors and the key analysts there about the progress there. But today we are really moving ahead for that particular BLA into Q3 2021. Now your second question was around the multi-cohort study. AJ, do you want to address that one?
AJ Joshi: Sure. So this is a study – it's a good question. This is a study that had some COVID-19 impact in terms of the initiation of our sites. So we have not enrolled a patient yet. However, we have really started activating initiating sites at a very good pace now. The early pace was slow related to COVID-19 because this was a study that we were starting up in the middle of COVID. So that's where we took the bit of an impact, but the most recent scenario has been that we've opened up a bunch of sites. So we would expect now the enrollment to get onto the pace that we were anticipating, and that still leaves us with the same target timeline that we've given previously of data coming out, which is 2023.
Pascal Touchon: Does it answer your second question, Jon?
Jonathan Miller: Yes, absolutely. Thank you. And then on mesothelin?
Pascal Touchon: Yes, the first question on the meso CAR T and what to expect at the end of the year, Jakob?
Jakob Dupont: Absolutely. So as Pascal mentioned in the introductory remarks, we have enrolled the first cohort on the mesothelin, the autologous CAR T the 2271 program. And so we're certainly collecting safety data there. We will also have tumor assessments. Of course, these are relatively small cohorts of patients, but we will certainly get response data. Tumor assessments are built in at regular intervals in the protocol, and we will also get some sense of how long the patients stay on study. And then some of the translational elements around persistence of the cells in the bloodstream of patients will also be something that we'll be able to report out on as well.
Pascal Touchon: Yes. And then I will add that this is a very exciting type of clinical data because that's for the first time ever that a CAR T with a PD-1 DNR and 1XX as a co-stimulatory domain is being used in patients in the U.S. So we’re all very eager to get view of the data and to share that with you at the appropriate time, because we think that's very exciting as we believe that we are really building these CAR Ts with the mesothelin binder, the scFv, the PD-1 DNR and IXX are the best way to address solid tumors. And of course, today's advanced mesothelioma, where we are testing the product in. But beyond that, we intend to go in other type of tumors. So very exciting time indeed.
Operator: Our next question is coming from the line of Anupam Rama with JPMorgan. Please proceed with your question.
Tessa Romero: Hey, guys, how are you? This is Tessa on the call tonight for Anupam. Thanks for taking our question. So just one from us, we're thinking about the commercial potential of ATA188 in MS. As it stands today, is this a program that Atara is thinking about partnering ex-U.S. say in Europe, similar to what you guys are planning to do for tab-cel? Thanks so much you.
Pascal Touchon: Thank you, Tessa, for your question. I’ll answer it. So we are now in Phase 2 in this randomized controlled trial. We’re also moving ahead on a lot of translational work that is pretty exciting. And we will come in first half 2022 with the interim analysis data, plus some other data that we believe will allow different things. One is of course, this discussion with the FDA on the potential to transform this Phase 2 into Phase 3 and discuss about further steps in a pivotal study. But we think it would be the right time also to discuss this data confidentially with potential partners, and we are already engaged with a number of companies. And as I said during my remarks, a number of them are extremely excited about this potential for ATA188 to be a big game-changer in the field of MS there. So these discussions are progressing. We have further data there. But the idea is that we believe we will benefit in terms of value creation from adding a partner for us, with us, for this pivotal study type of program to address not only pivotal in PMS, in progressive MS, but also pivotal in relapse emitting MS, where we believe the product has a great potential as well, and maybe some other disease there. So I think a partner will be important. And we are not at this stage going to communicate on what type of partnership, but let's just say that this is a partnership we believe will allow us to accelerate and expand the development of ATA188 across different type of indications, but at the same time preserve value for Atara and our shareholders for these potential game-changer in the field of MS and autoimmune disease. Does it answer your question, Tessa?
Tessa Romero: Absolutely. Thank you so much for taking our questions.
Pascal Touchon: Thank you.
Operator: Our next question is coming from the line of Phil Nadeau with Cowen and Company. Please proceed with your questions.
Phil Nadeau: Good afternoon. Congrats on the progress and thanks for taking our questions; a few from us. So first on tab-cel, we're curious whether you'd be willing to provide any more detail on what remains to be aligned between Atara and the FDA on compensability. And if not maybe just broadly as we think about allogeneic cell therapy products, what are the key elements of characterizing comparability between one production batch versus another, or cells that are manufactured by one group versus another?
Pascal Touchon: Thank you, Phil, for your question. Jakob, do you want to start, and I'll follow-on?
Jakob Dupont: Yes, absolutely. So when we – in our discussions with the agency about comparability, we're focused on the discussions regarding the pivotal material that we used in the ALLELE study and then the commercial material. And in point of fact, there are some very small differences actually between the pivotal material and the commercial material. It's really just refinements that we're making. So we believe that we actually have a very strong data package supporting the comparability of the pivotal material to the commercial material. And yes, there are a few refinements that have been made to get this product up to the GMP level for commercialization as well. So again, we think this is manageable and we have a strong case.
Pascal Touchon: And maybe what I could add, Phil, that while at this stage we cannot share specifics of this ongoing dialogue with the FDA. Maybe I can give an example of the type of topics that we are discussing with them. That example would be the number of manufactured lots to be included in an allogeneic cell therapy comparability study. I think we shared in the past that we have analyzed for each process version 15 lots per product versions of our – in our comparability study, which, on one hand, is much, much more than the typical free lots that one will have to use for comparability studies for small and large molecule type of product. And it's less than what autologous CAR T will do because for autologous CAR T as you know, each patient requires his own unique manufacturing lot, and that's why they have more – as many patients as they have in a study, they have a lot of patients. We are different there, and that's the whole purpose, by the way, of allogeneic cell therapy. It is to treat many patients with one manufactured lot. So you can have fewer lots being manufactured, and you have lower cost of goods and more accessibility and availability of therapies for patients. So we believe 15 lots is significant for such allogeneic cell therapy, particularly in the context of a rare disease, and that's why we feel strong about this robustness of our data package there. So that gives you an example of the type of discussion we have with the FDA to make sure that it applies to tab-cel, and also, it's in line with what is the fundamentals of allogeneic cell therapy. Does it answer your question, Phil?
Phil Nadeau: Yes, that's very helpful. That's perfect. And second question on the Q2 data cut that you noted would complete Module 5, the Clinical Module. What determines the timing of that data cut? Does there – is there a safety one and maximum time that laps from the data cut to the completion of the filing? Or is it some other element that determines when exactly you make that data cut?
Pascal Touchon: Yes. AJ?
AJ Joshi: Yes. Thanks for the question. I think the data cut timing is really based upon the prior discussions we've had with FDA on the amount of data that they wanted to complete the filing. So remember, they were looking for specific numbers of patients with a specific amount of duration of follow-up, so the data cut is timed to ensure we have the right amount of data to complete that filing.
Phil Nadeau: Perfect. And last clinical questions on the mesothelin program. What do you imagine would be the path to market for ATA2271? Do you think that what we saw from the initial CAR Ts in B-cell malignancies is reasonable, meaning like a single-arm study in a very severe patient population? Or would you expect something more rigorous?
Pascal Touchon: No. I think it's a good question. I'll start and Jakob, you – or AJ, you might want to chime in there. I would say, in the CAR T space, it depends very much on the indication and what's available for that indication there. So in advanced mesothelioma, for example, there is a clear medical need with no treatment that is able really to allow for long-term control of the disease in these patients there or elimination of the disease there. So having treatment that is having a very impactful effect in terms of objective response rate, in terms of MR assist, in particular, and then adding duration of response is what usually allows the FDA to accept that as a pivotal to go-to approval. It has to be really this time high-level of objective response and duration of response. Now to move beyond that into situations where there are existing therapies, that's where there might be a need at some stage for the CAR T field to go into more comparative type of studies. But the way we see right now, the first type of clinical work with ATA2271, this is addressing patients that have limited options and hence, having high-level of objective response rate as well as duration of response, means that this could be discussed with the FDA for potential submission there. I don't know whether Jakob or AJ, you want to add anything to that?
Jakob Dupont: Yes. I completely agree, Pascal, with the statement. And I do think in mesothelioma, there is a treatment paradigm focused, obviously, on chemotherapy. But we know the checkpoint inhibitors, the PD-1 access drugs do have activity here, but again, focusing on that unmet need, those patients that really don't have any more treatment options, that is the best path now. As we've also described for ATA2271, it is a mesothelin antigen directed CAR T. It also has 1XX, which we think is going to be a preferred co-stimulatory domain for persistence and activity of that CAR. But the other key point here is that we've built in PD-1 dominant negative receptor into that CAR T, so you're intrinsically providing and overcoming of the immune suppression that the mesothelioma is providing through PD-L1 tumor expression. So the fact that this is built into the cell, we think augments the chances of success here. But I think from a development standpoint, by far the clearest path to rapid approval is to go into a late-line unmet need population single-arm study response rate duration of response.
Phil Nadeau: Perfect. That's very helpful. And then last question is just a housekeeping question on financials. You had about $3.6 million in revenue this quarter from the Bayer collaboration. Was there anything special about the amount of activity you did for Bayer in Q1? Or should we assume some similar amount of revenue in all quarters going forward?
Utpal Koppikar: Phil, it's Utpal. Thanks for that question. We have roughly $70 million of deferred revenue on our balance sheet, and it's going to be a bit choppy in terms of how this revenue gets recognized in the P&L. So as you start to model it out, it's a level of effort that we're putting into delivering on the commitments to Bayer. So this $70 million odd you should see come through the P&L over the next two to three years. That's what we should be looking for.
Phil Nadeau: That's very helpful. Thank you.
Operator: Our next question comes from the line of Salveen Richter with Goldman Sachs. Please proceed with your questions.
Elizabeth Webster: Hey, good afternoon. This is Elizabeth on for Salveen. I guess just a broad question here and how you're thinking of allocating resources in the context of expanding the tab-cel program, running the MS program, and then also the emerging mesothelin CAR-T program. How all of these are developing in parallel? Thank you.
Pascal Touchon: Thank you, Elizabeth, for your question. I'll start and Utpal might want to chime in there. It's an important question because we are moving into not only commercial stage, we expect next year for tab-cel, but, of course, pivotal development of ATA188, and then further clinical studies with our allogeneic CAR T portfolio there and pipeline. So the way we see it is for tab-cel it's relatively clear that we have decided to partner for Europe, so we are now actively discussing with a number of companies, so it's moving very well indeed. And so the idea will be that we won't have any expenses linked with Europe for tab-cel because that will be covered by the partnering there. For the U.S., we have decided to launch ourselves, so we are starting to invest progressively into some activities, and that will progressively go up in time to be ready for the launch, possibly in 2022 there. So we believe that we have the approach that makes sense to make it a successful launch in terms of the balance between investment and a return on investment there. And we have a very detailed plan put together by Kristin Yarema, our Chief Commercial Officer, for that. So that's for tab-cel, so we are controlling well the situation there. For ATA188, as we said, moving into pivotal studies, especially if we want as we aim at to make that a big game-changer in the field of MS and autoimmune disease, that's where we believe we'll need a partner to go into that. And that's why we believe a partner in 2022 will allow us to accelerate and expand pivotal study across many indications for ATA188. At the same time, we're also investing in new manufacturing process, which we believe will allow us with stirred-tank bioreactor to cover a large number of patients with a low cost of goods. So that's really a significant investment in ATA188, which is really going to pick up next year, but that's going to be aligned with partnering with a large company there. Now on the allo CAR T, on one hand, we have the mesothelin CAR T franchise, for which we have already a partnering in place, and that's being funded really by Bayer there. And then for ATA3219, we can fund the next stage of development to be able to go to the clinic next year and to prove that we have here a potential best-in-class in B-cell malignancies. And then we have a number of other programs that are early stage and might move to IND-enabling studies over the future. And in that case, we believe that we will be well-funded to be able to pursue these programs. So clearly, today, the key in terms of resource allocation is to get to the finish line with tab-cel, have a partner in Europe, launch by yourself and create revenues opportunity and profitability progressively in the U.S. and then on ATA188, which is the second big type of investment needed over the next two years, this is really going to rely on partners. And we are very confident on finding a partner there because if we are right, everybody will want this type of product because that's really what everybody is waiting for, something really new, very transformative in MS, this is something in high demand. Does it answer your question?
Elizabeth Webster: Yes, that's helpful. Thank you.
Pascal Touchon: Thank you.
Operator: Thank you. Our next question comes from the line of Matt Phipps of William Blair. Please proceed with your questions.
Matt Phipps: Hi, guys, thanks for taking my question. I'm hoping you can kind of clarify some things with me, because when I go back and look at your January regulatory update press release and your Q4 press release, all the talk of CMC and Module 3 is related to the comparability between non-pivotal study and pivotal study. And there was a lot of discussion on whether this was going to be looked at parallel or pooled. And now you're saying that it's more an issue between the product used in the pivotal and the intended commercial product, so this seems like a much different issue. And I'm wondering if the original issue has been resolved and if this one has just recently come up, or if there are any other details you can give us on that?
Pascal Touchon: Yeah. Thank you for your question, Matt. Jakob, do you want to start and I'll chime in?
Jakob Dupont: Sure, absolutely. So thanks for the question, Matt. So what – they're really related questions here because the comparability issue of pivotal to commercial that needs to be solved for the sake of the BLA filing now and we're focused on that particular part. So once we have the discussions with the FDA and we've come to agreement around those comparability aspects, they are going to be applied to the same topic when you think about the historical to the pivotal. So this is really all part of the same discussion. Now we are focusing particularly on pivotal to commercial because that is – there we're getting all of the information that's going to help and form this other topic of historical to pivotal.
Pascal Touchon: And I will add that it was really in two steps, that's why the communication has been in two steps, Matt. I mean there was a first step back in the fall where we were discussing with the FDA regarding different aspects of what will be needed for submission, but we provided them with data showing, we believe, comparability between historical and pivotal. Now since then, we've had as we said during several Type B meeting and formal calls, to discuss about something else, which is the Module 3 CMC. And in any Module 3 CMC, one needs to show comparability between pivotal and intended commercial, that's a prerequisite to file a BLA. So it was really two steps in terms of the discussion with the FDA, and that's why the communication is evolving now. We are really focusing on that one, but solving that one and we believe we are making great progress there, will anyway, also answer the other one because it's about the methodology and the type of data that we have on comparability. So it really was two steps. And it's really since January that we have had all these specific interactions as part of a BTD status with the FDA and progress made on this aspect that is essential for the Module 3 because you need to have this comparability fully aligned with the FDA to be able to move forward there with the BLA. Does it make sense, Matt?
Matt Phipps: I mean, that helps. And I get that it's all related. But I guess, back in the fall and early in January, when it was talk of non-pivotal versus pivotal, had you yet, at that point completed your I guess 15 lots of commercial product to show to the FDA? Or is that something that you have now recently shown them and they are now questioning the comparability of that to the pivotal study?
Pascal Touchon: Exactly, it was in two steps. First step was, and you may remember when we said last year, back in September, we had a Type B meeting, where we provided comparability data between historical and pivotal. Second step has been since then that we've provided them and we started to discuss that we had a Type B in January, talking about pivotal to commercial. So it was a second set of data and then we have had a further discussion with them based on their guidance with one new analysis and so on. So that's the second step of discussion that's been based on pivotal to commercial.
Matt Phipps: Okay. I mean, I guess that's the reason you've done 15 lots of comparability for the – or I guess, that's all commercial product is because you're seeing higher-than-expected variability as you trying to compare this to the pivotal or non-pivotal?
Pascal Touchon: No, there was not a higher variability. I mean, the 15 lots has been based on statistical methods there to be able to show equivalence based on value statistical tests there between two-type of process versions there. And the 15 lots has been done for historical, for pivotal, for intended commercial there. So the 15 is not linked with a particular aspect, but statistical power to be able to show equivalence between these different process versions.
Matt Phipps: Okay. Also, the wording specifically now states methodologies to assess comparability. I assume this is methodologies with data that you have already generated and not something that has to be done as a new analysis or something like that.
Pascal Touchon: Yeah. I think we provided the FDA with methodology from the point-of-view of statistical analysis and other type of aspects of that methodology on the data on these manufactured lots with different process versions. And the alignment that we are having with the FDA is around these methodologies. And again, I'd like to remind you that we are the first in kind. Nobody else has been coming to the FDA with that type of allogeneic cell therapy. So as I said, with the example of sample size, the FDA asked to align with us being the first about the number of samples – number of lots that make sense for an allogeneic cell therapy because nobody else has been to that level with the FDA. And I gave that example that is for a small molecule or large molecule comparability study, you need three manufactured lots. For an autologous CAR T, you have to provide as many as you manufacture treating patients, and it's one lot per patient. So if you have a study with 60 patients or 100 patients that mean you have 60 or 100 lots. In allogeneic cell therapy, it's different. We believe 15 is very significant, much higher than the three that is being used with molecules. And at the same time, it's something that is powered from a statistical point of view to be able to address the variability in a run-through cell therapy.
Matt Phipps: Okay. And then I guess, I think last question. The wording has also clearly changed from on-track to complete a rolling submission by Q3 to now working toward completing a BLA in Q3, no mention of rolling. I assume this is just kind of getting things closer to Q3, in general, where you're not going to even do a rolling submission; you have to submit it all in Q3. Is that right?
Pascal Touchon: We can still have a rolling submission. It's not that we cannot have a rolling submission. It's just then there will be some time where we can hold the submission and then complete the submission with the clinical module and altogether we think that we are working through all this Module 5 as you know, that's based on the data cut and the analyzes in Q3. While we are working on Module 3 so it depends when we have that alignment with the FDA on comparability, so then that means the Module 3 can be finalized but there is nothing discussion with the FDA that say that we cannot do a holding BLA, just to be clear.
Matt Phipps: Okay, thank you.
Operator: Our next question is coming from the line of Tony Butler with ROTH Capital. Please proceed with your question.
Tony Butler: Yes, thanks a lot. Pascal apologies I was just disconnected a little bit and you may have said this, so please forgive me, there are really three questions. One is Jakob alluded to enrolling sites for ATA188 very, very rapidly, in clinicaltrials.gov it was 17, is that a fair number or would there be more sites to be added. That's question one. Number two, Pascal, you set up a little bit of a trial balloon on 188 suggesting that there was a great deal of I think your phrase was large company interest in 188 and that implies partnership, but I just wanted to know what you were thinking around 188 longer-term? And the third question involves 2271 or importantly the relationship with Bayer is that relationship because they are responsible for filing the IND, as well as eventually commercialization, will you all be doing the manufacturing. I'm just trying to separate church and state there with respect to that program. Thanks very much.
Pascal Touchon: Thank you, Tony for your three question. Maybe the first on AJ you want to address it from the number of sites.
AJ Joshi: Sure, absolutely. So, you're asking whether we are continuing to enroll and activate more sites and the answer is absolutely yes. We've got sites open now in the U.S., and in Australia and we're continuing to add more U.S. sites, and we'll also be opening up Canadian sites over the course of this year as well.
Tony Butler: Thank you.
Pascal Touchon: Regarding the ATA188 partnering aspect I mean the discussion we are having with some companies is really around establishing the type of framework from partnering that will create significant value for the company and our shareholders. And at the same time allow us to expand and accelerate the development of these potentially transformative treatment there. So that's the type of thing that we're seeing that clearly as I trying to explain earlier on moving into pivotal studies in PMS in relapse remitting MS maybe in some other type of autoimmune disease where you have a link and association between EBV and the disease such as lupus, RA that's required some partnering because that's a very significant efforts with ALLELE but partnering should be done in a way that preserves value for the company and our shareholders. So that's the overall framework and I cannot give you more details about that. But of course we are working actively on these type of framework there. Now, Your last question for 2271 maybe to clarify, 2271 at this stage, this is the autologous version. So the IND is run by Memorial Sloan-Kettering and we are funding that and of course we have access to these. Now moving forward in that development, there will be a need for someone else to move forward, if it goes into further development and that's the plan to have Bayer as a partner there to move forward for 2271. Meanwhile, as we know, we are working toward the IND for 3271, the allogeneic version and this one we are doing the work right now but Bayer and that's part of the deal Bayer will be the company filing the IND, we believe it could be in Q2, Q3 next year and then developing the product and then commercializing the product. So at this stage the work done by Atara is really to support the first in human study for Memorial with 2271 at the same time worked on the allogeneic 3271 IND enabling studies to be able then to provide a partner with the right set of data to move forward toward the IND. Does it answer your question?
Tony Butler: Thank you. Yes, it does. Thank you very much for the time.
Operator: Our next question comes from the line of Ben Burnett with Stifel. Please proceed with your question.
Ben Burnett: Hey, thanks very much. I just wanted to ask a few questions about commercialization plans for tab-cel and I guess specifically what capacity do you expect to be at on approval, just in terms of the size of the cell banks. And then secondly, I guess is there any unique thing that needs to happen here to certify on board hospitals. I know that you guys use the Atara MatchMe delivery process. I'm just curious how easy it is to adapt that to new sites and if there is any certification process like we've seen with some CAR-T programs.
Pascal Touchon: Thank you Ben for your question. Kristin, do you want to address that question.
Kristin Yarema: Sure, absolutely. And thank you for the question. So, as we said before, we are on track building inventory, so we expect at the time of launch and soon thereafter to be able to address about 95% of patient needs with our capacity, our inventory. So that's very exciting for us. And again, we're well on track with that. In terms of some kind of certification requirements or the model we're doing a lot of work with institutions right now, really going in and doing research with pharmacy directors and cell labs at an individual level and we are not anticipating that will require extensive certification requirements. In fact, that is one of the things that we think is quite exciting about our model.
Ben Burnett: Okay, thanks for the color. Appreciate it.
Pascal Touchon: Yeah. And one thing, it's important also to clarify maybe Joe might want to comment on that because the differences between the pivotal process version and commercial process versions are minimal there, that's why we are confident in terms of comparability. That's why we are also confident in terms of building inventory. Joe, do you want to comment on that?
Joe Newell: Absolutely. Pascal, I think then the other aspect of it is just, we've seen great process control across all of the process version, supporting commercial and the clinical product we're seeing there, we're seeing increased yield production. So to that point of building that inventory, very confident with what we have already made and released to support pre-commercial inventory. And we've seen the same level of process control and manufacturing robustness as we continue to build out that library.
Ben Burnett: Okay. Okay, got it. Great, thank you.
Pascal Touchon: And Joe on the differences between the pivotal and the commercial.
Joe Newell: Yes, absolutely. I think it is still minimal. Quite honestly the change was made, it was generally made to support the commercial GMP compliance requirements to support the BLA. I'll give an example. We moved the manufacturing site for our EBV viral reagent from a CMO to our own facility in Thousand Oaks. We did that for two reasons, one better control of our supply and then most importantly to ensure that we can meet the commercial GMP compliance requirements in support of the BLA from that facility. So again, minimal changes and generally if the change was made it was made to support the BLA's success.
Pascal Touchon: Thank you Joe.
Operator: Thank you. Our next question comes from the line of Yigal Nochomovitz with Citi. Please proceed with your question.
Carly Kenselaar: Hi, this is Carly on for Yigal. Thanks very much for taking our questions. We have a couple on the CAR-T pipeline specifically on ATA3219 the CD19 program. We're just curious if you had considered incorporating the PD-1 dominant-negative receptor into the CD19 program as a potential strategy for boosting persistent. Obviously, it's incorporated into your mesothelin program so we're just wondering if you could kind of expand on the rationale for including in the mesothelin and CAR-T, but not for CD19.
Pascal Touchon: Thank you Yigal for your question. Jakob, do you want to address that one.
Jakob Dupont: Yeah, thanks for that Carly. So in terms of liquid tumor targeting product like 3219 it makes sense obviously for the binder to begin CD19 as we target these cells. It also makes sense for 1XX to be in there as we think this is a potentially best-in-class co-stimulatory molecule. But the PD-1 DNR is not as useful in the context of liquid tumors because if you think about the mechanism of immune suppression that occurs in solid tumors, there is the creation of the PD-1 protein by the tumor that prevents the T-cells from really having their fight against solid tumors. But that's really not in effect that you find in liquid tumors. And so there is really not a good need to put the PD-1 DNR into the 3219 specifically because it is targeting B cells that express CD19 in this regard. Now, we do think the other aspect about 3219 that is so compelling to us is the fact that we're using our allogeneic EBV specific T cell because what in essence you have as you've got a T-cell a CAR-T cell that will target CD19 on the B-cell malignant cells, but the EBV specificity the native EBV TCR that is in these allo T-cells is one that's actually complementary in this setting, you don't need to delete that T-cell receptor with something like CRISPR Cas9 and so forth. So it actually leads these allogeneic T cells more intact by leaving the native TCR in place which is specific for EBV. So we think that the performance is part of the reason why we think 3219 could be best-in-class is not only because of the 1XX but also because of our EBV T cell specificity of those cells.
Carly Kenselaar: Got it. That's really helpful. And then I guess just sticking with 3219 as you start to think about sort of their initial clinical development plan can you share any preliminary thoughts on the Phase 1 trial design particularly regarding types of B-cell malignancies that you plan to enroll whether you would plan to study 3219 in patients previously been treated with a CD19 targeted therapy and any early thoughts you have on lymphodepletion would be helpful. Thank you.
Pascal Touchon: Yeah, Joe do you want to start off.
Joe Newell: Yeah, I can start for sure. So, we will do, obviously a classic dose escalation and expansion study in that Phase 1. We get as we announced last year have a good pre-IND meeting with the agency. That was very successful last year, so we had some early discussions around the Phase 1 clinical trial design, but we have not per se spoken about the details and it's still an area of refinement that we're working on now but certainly CD19 expressing B cells malignancies will be the target there. And we think there are some very interesting opportunities again because of the 3219 molecule or product where we think there is going to be better persistence here, but because it's allogeneic there are some other things that you can consider including potentially re-dosing of patients as well. So, there is a lot of flexibility with that program, and we're going to refine the clinical trial design in the coming months.
Pascal Touchon: I think the other aspect maybe to add on that is, so far whether it's autologous CD19 CAR-T or first kind of initial data with lack of durability proven so far of other allogeneic technologies and CD19 the level of response if you look at DLBCL already not follicular which is different, the level of response has been more on the 40% in terms of long-term response, long-term CR, because here you need CR in these type of patients there. So we believe there is still room to have a best-in-class with higher level of response. At the same time durability of response, because the intent is to really have long-term durability of response with the curative intent type of this product and then of course, a better safety than the autologous. So all of these aspect where we think or approach might bring some interesting data we need of course go to the clinic there but from the way we've built the product, we think that we could address this medical need in terms of response rate, safety, and durability of response. Does it answer your question Carly?
Carly Kenselaar: Yes, it does. Appreciate all the detail. Thank you for taking the questions again.
Pascal Touchon: Thank you.
Operator: Thank you. Thank you for joining the Atara Biotherapeutics first quarter 2021 financial results conference call. You may now disconnect.
