Atara Biotherapeutics, Inc. (ATRA) on Q3 2021 Results - Earnings Call Transcript
Operator: Good day, ladies and gentlemen, and welcome to Atara Biotherapeutics Quarter Three 2021 Financial Results Conference Call. At this time, it is my pleasure to turn the floor over to your host Eric Hyllengren, VP, Investor Relations and Finance. Sir, the floor is yours.
Eric Hyllengren: Thank you, operator. Good morning, everyone, and welcome to Atara's third quarter 2021 results conference call. Earlier today, we issued a press release announcing our third quarter financial results and operational progress. This press release and an updated corporate slide deck 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; 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 morning. We continue to make meaningful progress across all three strategic priorities, tab-cel, ATA188 in multiple sclerosis, and our next generation allogeneic CAR T programs. Today, we announced for the first time positive top line data for more pivotal Phase 3 ALLELE study for tab-cel in EBV positive PTLD, which includes new analysis, additional patients and extended follow up. These data confirm a strong objective response rate of 50% with clear durability of response and overall survival of 89% at one year in responders, while still demonstrating well tolerated safety profile in line with prior results. These data will be a basis for the imminent MAA submission in the EU and our plan BLA submission in the U.S. next year for patients with EBV positive PTLD. We are very excited to submit in the next few days of filing for approval in Europe and we've all recently granted accelerated assessment, we anticipate a decision regarding EU tab-cel approval in the second half on of 2022. Additionally, in October, we were extremely pleased to announce our exclusive commercialization agreement with Pierre Fabre for tab-cel in Europe, Middle East, Africa and other select emerging markets for EBV positive cancers. We believe this partnership reinforces the commercial opportunity for tab-cel in these markets and maximizes the strategic and financial value of this potentially transformative therapy. On the U.S. regulatory front for tab-cel, we continue to make step-wise progress for type B meetings with the FDA. In particular, we have aligned with the FDA on comparability approach including the statistical methodology. Based on the new request from the CMC review team following our recent interactions, we will provide the agency additional analysis of CMC data we have already submitted. We plan to have further interactions with the FDA in Q1 2022 to resolve the outstanding items and expect to complete the BLA submission for tab-cel in Q2 2022. Concurrently, we continue to work on pursuing the development of tab-cel in additional EBV patient population with a primary focus on immunodeficiency associated leasehold proliferative disease IALPD. Enrollment is continuing at in the label expansion multi cohort study which is evaluating six patient populations, including four within IALPD and two in other EBV driven disease in the U.S. and in EU. The multi-cohort study data is expected in 2023 and we believe this could be a meaningful label expansion opportunity. Turning to ATA188, our potentially transformative therapy for patients with progressive multiple sclerosis. Last month, we presented at ACTRIMS a decade Phase 1 open label extension or OLE data in patients with progressive MS fitted with ATA188 for up to 39 months. As a reminder, the natural history of patients with progressive MS is continuous disability progression. The OLE data we presented demonstrate that patients have achieved sustained disability improvement or SDI at the higher rate and longer duration that would be expected based on this naturally story. The majority of SDI seen in the data presented is driven by sustained EDSS improvement which is our primary endpoint in our Phase 2 randomizes of so-called EMBOLD study. Additionally, we presented Magnetization Transfer Ratio MTR data and making biomarker considered to reflect the state of the nation in the central nervous system. This statistically significant increase in MTR parallels the EDSS improvement observed and provide evidence than pre-the-nation maybe the driver for clinical improvement. These potential biological basis for clinically significant EDSS improvement observed with ATA188 continues to build awareness and interest in the transformative potential of ATA188 in the medical community and with potential partners. As a reminder, in the first half of 2022 we will conduct an interim analysis or IA to assess the efficacy and safety and we plan to disclose of decision regarding the next steps for the program. And or rationale for this decision based on data from the IA while still maintaining the integrity of the study. We believe these IA will be an important milestone for the company, investors and potential strategic partners. With regard to our CAR-T portfolio, our mesothelin product candidate ATA2271 and ATA3271 partnered with Bayer are progressing well. Our collaboration at Memorial Sloan-Kettering will present preclinical, clinical and translational data from the lowest dose cohorts of the open label, single-arm Phase 1 clinical study of ATA2271 and auto therapy targeting mesothelin to a mini oral presentation at ESMO IO in December '21. Meanwhile we continue to make progress on IND enabling studies for ATA3271 and another shelf allogeneic CAR-T therapy targeting mesothelin using next generation PD 1 dominant negative receptor and 1XX CAR co-stimulatory signaling domain technologies for which we anticipate an IND filing in the second half of 2022. Additionally, we plan to present new preclinical data both I mean potential benefits in solid tumors for ATA3271 at SITC in November. Turning to ATA3219, our allogeneic CD19 targeted CAR-T for patients with B-cell malignancies. We expect to submit an IND in Q1 2022, ATA3219 leverages our next-generation 1XX CAR co-stimulatory signaling domain and allogeneic CD19 targeted CAR T cell platform and is a potential best-in-class therapy that does not require TCR or actually gene editing which we believe is a key differentiator, of our platform. To further support of defaulted allogeneic off the platform we have invested in new capabilities to support our product pipeline and further drive innovation by opening on new Atara Research Center or ARC in further north to house or translational and preclinical science, process science and analytical development teams. Our talented team at this new facility will support our product pipeline and further drive innovation by leveraging our unique and differentiated allogeneic cell therapy platform. Moving now to our financials, with regard to our cash position and runway, we ended the third quarter of 2021 with 357 million in cash. This includes 46 million for the sales of shares of common stock to go ATM facility. We believe we are sufficiently funded in the second quarter of 2023 with this cash and the $45 million of pump payment received in the commercialization agreement. As we head into the final months of 2021, I'm proud of the Atara staff and partners of steady progress in improving the lives of patients with serious diseases. We are very close to filing the NDA in the EU for tab-cel, the first of application for an allogeneic T cell therapy in the world. And our progress in ATA188 clinical study could bring a truly transformational therapy to MS patients. We look forward to providing more update to you in the coming weeks. I will now turn the call over to Jakob. Jakob?
Jakob Dupont: Thank you. Pascal. I like to add further color on the progress we made during the third quarter in advancing our three strategic priorities. As Pascal mentioned, today we announced the first presentation of new positive data from the pivotal tab-cel Phase 3, ALLELE study in EBV positive PTLD confirming a strong objective response rate or ORR durability of response and continued well tolerated safety profile which support the imminent European M&A submission and plan BLA submission. These data will be presented at an oral session at the American Society of Hematology Annual Meeting next month. In these data, we observe a 50% ORR as measured by independent oncologic response adjudication with the response of 50% at both PTLD following SOT and PTLD following HCT. This response includes both complete and partial responses. Importantly overall median time to response was 1.1 months, which is critical in this setting where patients are in urgent need of treatment as they only have a few months to live. Of 19 responders at this point in time, 11 have duration of response lasting more than 6 months with a median duration of response, not yet reached. The one-year survival rate was 61% overall, 57% for SOT, 67% for HCT. Those who responded had a longer survival compared to non-responders with a median OS not reach and one-year survival rate of 89% compared to 32% in non-responders. Safety findings were consistent with previously published data with no reports of tumor flare reaction and no confirmed evidence of graft versus host disease related to tab-cell treatment. Next month at ASH, we will present additional data on tab-cel through several abstracts, including a second oral presentation on long-term survival from Phase 2 and multicenter EAP studies in relapsed-refractory EBV positive PTLD showing median overall survival of 54 months and OS at 2 years, reaching over 86% in responders or patients experience CR or PR. As a reminder, both pivotal data from the ALLELE study and historical data will be included in the regulatory filings of tab-cel. We believe the tab-cel is a truly transformational therapy for these patients with EBV positive PTLD with a median survival is just a few months for patients who have progressed on one prior line of therapy and the data we have shown today serves to deepen our conviction around the potential benefit the tab-cel can bring to patients. Regarding the tab-cel regulatory discussions in the U.S. as Pascal mentioned, we continue to make good progress with the FDA. We held a Type B meeting with the FDA's CMC review team in October and we achieved agreement on comparability approach including the statistical design to assess comparability between pivotal and commercial tab-cel products. Importantly, the FDA has not requested additional new studies or manufacturing lots. We are planning to submit additional analysis and data already submitted to the FDA at their request. We plan to interact with the FDA in the first quarter of '22 regarding these analysis to gain agreement on comparability for pivotal to tab-cel. We've also shared the clinical data from the pivotal ALLELE Phase 3 study along with data from supportive and historical studies. We received productive feedback from the agency that will help to guide the structure of our BLA filing. Following agreements on comparability, we plan to have a pre-BLA meeting prior to submitting the BLA for tab-cel in the EBV positive PTLD in the second quarter of 2022. Moving to ATA188 our product candidate for multiple sclerosis. At ACTRIMS last month, we presented encouraging 2-year clinical data from the Phase 1 open label extension and new translational MTR data from the Phase 1 study of ATA188 in progressive MS. As context, patients who have progressive MS will unfortunately only continue to worsen over time as the disease progresses. If there was a treatment that offer the possibility of maintaining the current level of physical function, it would have a tremendous impact on these patients' lives. As we saw in the clinical data presented at ACTRIMS most patients in OLE were progression-free. Taking a step further, the prospect of a treatment improving a patients disability would be even more transformational for them and has never been seen before. The data we presented at ACTRIMS showed that 7 of 8 patients was sustained disability improvement or SDI in the Phase 1 or open label extension SDI was maintained at all subsequent time points up to 33 months with multiple locations regaining enough function that they no longer needed to a walking aid and were able to watch a few hundred meters unassisted. With regard to the presentation of new MTR data, there is an increasing body of scientific evidence using MTR as a key measure of remyelination in MS. In patients treated with ATA188 who achieved sustained EDSS improvement versus those who did not, MTR for non-enhancing T2 chronic brain lesions increased with the trend at 6 months that achieved statistical significance at 12 months. This significant MTR increase may be indicative of remyelination. A similar trend of MTR increase has also been seen in normal appearing brain tissue. The ATA188 Phase 1 MTR data assessing normal appearing brain tissue in PPMS and SPMS patients compares favorably to Siponimod data from their Phase 3 study in SPMS. This comparison is made on Slide 37 of our updated corporate presentation for which I'd like to highlight the following. We expect this course of MTR in progressive MS is declined or demyelination. As seen in the placebo group in the Phase 3 Siponimod study data, Siponimod showed slowing of demyelination based on the small decrease in NCR versus placebo. On the other hand, ATA188 uniquely indicates remyelination base on a relatively large magnitude increase in MTR. On Slide 38 starting at six months after ATA188 treatment in normal appearing brain tissue and Unenhancing T2 Lesions MTR is increased in patients with EDSS improvement and relatively stable in those without. This parallels the time course of clinical EDSS improvement. For the first time in progressive MS, ATA188 treated patients with EDSS improvement demonstrated a statistically significant increase in MTR in Unenhancing T2 Lesions in patients with EDSS improvement. This MTR analysis where the time course for increased MTR parallels EDSS improvement observes provides evidence that remyelination may be the driver for clinical improvement and supports a potential biological basis for the clinical EDSS improvements observed with ATA188. Moreover, these unique and finding suggesting remyelination has generated new investigator inquiries and excitement as we continue to enroll the Phase 2 randomized, placebo-controlled in both study. We believe this MTR data further support the probability of success of ATA188 as we head towards the upcoming interim analysis in the first half of 2022. Turning into our potentially best-in-class CAR T portfolio. As a reminder our approach does not require TCR or HLA gene editing. And presents a differentiated approach that in - that retains the endogenous T-cell receptor. This has been shown in academic studies to increased persistence, durability and trafficking. The safety and tolerability of our allogeneic EBV T-cell therapies and platform has now been supported by clinical studies and evidence and approximately 400 patients in various disease areas and our EBV platform that enables scaling of manufacturing in stirred tank bioreactors. In closing, I would like to extend my gratitude to the entire staff, our collaborators and the patients involved in our studies. Working together, we are hopeful that we will bring our transformative therapies to patients in need. I will now turn the call back to the operator to begin the Q&A portion of the call. Operator?
Operator: And our first question comes from Salim Syed from Mizuho. Go ahead.
Salim Syed: Yes, hi thanks guys for all the color and congrats on the progress. So, a couple from me on ATA188 so Pascal, Jakob when we get the data in the first half of 2022 historically in multiple sclerosis trials I think folks generally understand companies need two trial to file for regulatory approval. But progressive of multiple sclerosis there is also an unmet need and I think it's pretty established that you guys will let us know if you're going to have a large increase and here or a smaller increase? And I'm just wondering, is - a fair way to interpret this is that if you say hey, we're going to increase this by a large and that the P value, you're seeing is less than 0.01 and you only need one trial and if it's a smaller increase the P value there is something like you think you can get to a 0.05 or less and just wondering if you can actually give us that P value when you disclose the data? And then the second question, just more around the limited disclosure that we're going to get in the first half of 2022. Can you just remind us is this being driven by the FDA, where they've asked you to limit the disclosure or is this more an entire decision and the reason why I ask is, I think some investors would argue here that it's more capital efficient to disclose more data - I'm just sort of curious how conceptually you're thinking about that? Thank you.
Pascal Touchon: Yes, thank you Salim for your question and I will ask AJ to start answering there. I’m starting with the second question, because that will give color to the first one there AJ.
AJ Joshi: Sure thanks for the question Salim. Again starting by your second question, maybe you can just give an overall kind of view on this. So, as you know the IA for this, randomized placebo-controlled Phase 2 study, we're going to hit both efficacy and safety criteria as well as some additional biomarkers. And as you know, when we do the IA will have a range of results, everything from people who have been study for well beyond a year or with people with higher data around the three-month timeframe. So it's going to be a fairly large data set for us there. And the objective, as you kind of alluded to is to adapt the sample size, which at this stage is 80, but we could certainly - the plan is to potentially adapt it to a larger size, depending on the trend we're seeing and possibly discussions with the FDA. And what we're seeing is, we are in an incorporate form. We will communicate publicly after that IA is done both what we plan to do in terms of the adjustments and sample size as well as provide detail on the rationale that we're using based on those IA results. So we are going to provide some additional detailed rationale there. Now today, we won't get into the specifics - of the actual data that we're going to share because to some extent the actual data that we’d share will depend on the IA results, but we can't emphasize that the IA-based rationale for any adjustments we're going to make in EMBOLD study will be made clear. But we still have to maintain the integrity of that double-blind study in that kind of leads into our last question that you're asking. So maybe I can just give an example to add a little color to this, so what will providing and what we won’t be able to provide. So, at the time of the IA let's say we see a trend of EDSS improvement that in the active ATA188 arm, but similar to what we observed in the Phase 1a study. And then we see a trend for placebo that's pretty much what we expected in our modeling. So at that point we’d likely either decide to make no or minimal change in the sample size, except if we believe that once we have discussion with the FDA that we could transform the study into Phase 3, which will be of course of a much larger expansion. At that point then, we publicly disclose our decision we’d give a specific rationale around it without disclosing the detailed data, so we can preserve the integrity of the study. So this is really, again, it's really about, this is a strong robust Phase 2, its still fully placebo control, so – like an oncology setting and that’s what going to happen - as much as we can to maintain the entire with that study. So that's the main rationale behind giving the details on the rationale, but not details on the data itself. So that kind of leads into your second question about we’ll we be disclosing P values. We're not going to be discussing specific P values or the statistical methodology at this point for the study and we wouldn't be disclosing that.
Salim Syed: Got it.
Pascal Touchon: And again that study the aspects related to the specifics. We cannot give you the specifics at that time. All the actually information will share, because that specifics will be depending on the results and our discussion with the FDA, but we do plan to communicate enough to make sure that there is a clear understanding from investor community in particular about how meaningful is this particular milestone of this interim analyze is there.
Operator: And our next question comes from Matt Phipps from William Blair. Go ahead, Matt.
Matt Phipps: I just want to thanks for taking my question. Just wanted to clarify some of the regulatory discussions around CMC so any color on what the CMC team is focused on this point, because you said on the Q2 call that you're aligned regarding comparability approach. And so just kind of curious what additional information you’re looking for. And then again, just to make sure I understand the sequence of events correctly, you're going to submit this additional analysis that the FDA requested and then discuss that in Q1 will that be another Type B meeting or something informal and then hold a pre-BLA meeting in Q2?
Pascal Touchon: Thank you Matt and maybe I start and Jakob can chime in if needed there as you said, we have reached agreement on the methodology we presented during the recent Type B in October this new compatibility analysis and you may remember, we said in Q2. This is a new analysis based on analyzing all the batch manufactured by Atara this 74 batches there. So that's a lot of data that we sent with the FDA there. And we believe and we've shown in our analyzes that these set of data demonstrate comparability between the pivotal study process and the Internet commercial process I should say, keeping in mind of course as you may remember that in reality this process difference is between these manufacturing process there should minimum they are really minimum there. But we analyze all the batches presented all these data an immense amount of data to the FDA. So what the FDA has asked is additional data analyses related to a few attributes there and we will provide them because the data they have the data already, but they ask us to do additional analysis. So we’ll do with additional analyses we’ll provide the FDA with this analyses for which data I already submitted. And then once the FDA analyses we plan for further discussion. We are not commenting yet on the type of discussion, but Type B would make sense for sure of there. And then once we've got to that level of discussion and alignment with the FDA an agreement on the comparability, that's where, then we will go to a pre-BLA meeting to be able then to present all what we plan to submit including clinical and all the other stuff and then we'll be able to file for BLA. So that's the sequence of events there that we are planning based on this discussion with the FDA. Does it answer your question.
Matt Phipps: And then maybe on the kind of asked data, we'll see the way of study, maybe you can just. I don't think if you can say yet, but maybe how many patients received like a switch in cell line. And if that was included in the kind of these response rates can you remind me on that?
Pascal Touchon: Yes Jakob you want to answer that one.
Jakob Dupont: Yes so, Matt. Thanks for the question. So we haven't included that particular on detail in the abstract at this point in time. But what you can see here, and this is what we're reporting obviously is that we have a 50% response rate in all these PTLD patients and a 50% response rate in both HCT and SOT, and this is of course by independent oncologic and radiographic assessments so this is really independently reviewed. And I will say that most of the responses were with the first therapy. But of course we can switch slots, but those details were not included in the current abstract presentation.
Pascal Touchon: But you can expect it’s an all presentation at ASH. So you can expect much more detail at ASH.
Operator: And our next question comes from John Newman from Canaccord. Go ahead, John.
John Newman: Thanks for taking my question and congrats on all the progress, especially in Europe with tab-cel. The question I have - excuse me, in the past FDA has tended to look at durability at six months for CAR T products or T-cell products. In your case I think you provided some additional durability data to the FDA, but I just wanted to ask - my understanding is that the median follow-up for the study at this point is very, very long. And the reason I'm asking that is because I'm assuming then at this point the FDA may have all the data that they would want regarding the durability. But I just wondered if you could perhaps just comment a bit about the follow up for the study. Thanks.
Pascal Touchon: Thank you, John for your question. Jakob, do you want to take that one.
Jakob Dupont: Yes, sure absolutely. Thanks, John. So, as you recall, last year we disclosed that the data cut that we provided the agency with the number of patients, this is in October of last year, was a reasonable number from the FDA perspective. But they wanted this six months duration of response data, which again is required for regulatory approval, which is why we did this most recent data cut. And so we do again have this durability of response data. As I mentioned earlier in my comments that we think are quite encouraging. And I think the 89% survival of responders at one year is quite encouraging. So that's for the ALLELE study now. I also mentioned that we have a second oral presentation at ASH, which is on our historical and supportive studies. And there again we have median of 56 months of overall survival in that circumstance, which again is of course a very profound result for these patients. So I think the totality of the data between the ALLELE study and then the additional supportive data that will also be presented at ASH again shows a long-term benefit for these patients, where you get high response rates, a rapid response, a durable response and an impact on overall survival for these patients that have a really lethal disease.
John Newman: I have one additional question, just sort of a general question on ATA188. Just wondering if you could comment on the understanding that you have regarding the way the agency thinks about the potential for EDSS improvement versus simply slowing EDSS decline. I think the MS therapies that have been approved or progressive MS are simply slowing the decline. I'm just curious if you could perhaps provide some color on how the agency thinks about something like EDSS improvements?
Pascal Touchon: Thank you John for your question I'll start and A.J we’ll take up he might want to chime in. But I mean, that's why it was so important for us to have this dialogue with the FDA at the end of last year where we align on these primary criteria for EDSS sustained improvement at 12 months which is having two consecutive time points for improvement, and the last one being a 12-month there. That was very important, because as you say, it was not yet - no product has been approved and to our knowledge only one has try to develop on the EDSS improvement for the Phase 3 that was MDA study there with - unfortunately that study failing there. So it was very important there that we talk with the FDA and we align with them and they did say that sustainability improvement is an important primary endpoint for probably PMS. And the third was EDSS improvement that's why we change our primary criteria in the EMBOLD study to be sustained EDSS improvement. So that's the first nobody else has done that nobody else is trying to do that. Because even the few studies that are trying to go now in PMS, nobody is trying to look at the - sustaining EDSS improvement. So, but that's - first that has been in line with the FDA. Does it answer your question, John?
Operator: And our next question comes from Tessa Romero from JPMorgan. Go ahead.
Tessa Romero: A couple of questions from me this morning on the CAR T programs if I could so just thinking a little bit about the mesothelin CAR T program ATA2271 ahead of the updates coming up here at ESMO IO in December. What are you looking to understand in this data update and given what we know about from the prior MSK data and also your allogeneic program? And what would be a win scenario in your view here? And then my second question is on that ATA3271 allogeneic program, what are the gating factors to IND submission at this point? Thanks so much.
Pascal Touchon: Thank you very much for your question. Jakob, do you want to take the first one?
Jakob Dupont: Yes, absolutely so Tessa, thanks for your question. So as mentioned, we're excited to announce that we have a mini oral presentation with our collaborators at Memorial Sloan-Kettering for the autologous mesothelin program and again we think that our allo CAR T platform really is an exciting one and potentially best-in-class because we are leveraging technology like 1XX of next generation costimulatory domain and PD-1 dominant negative receptor. And of course this first study is for the auto program and then we have the following allogeneic one using our EBV T cell platform. And again, we don't do gene editing. And we think that that's really important for the performance of the sales until - limit risk as well. So at ESMO IO our collaborators, Sloan-Kettering will present preclinical data for the program, but also clinical data from low dose patients. So you'll see safety there translational data as well as some potential early efficacy I will say, of course, these are low-dose cohorts. But again, I would say, safety is really important here of course as we move into these CAR T therapies for solid tumors. And then, I also think, you know, these questions are persistence of the cells is really important. Turning on to the allogeneic program 3271 just one comment, we are having a presentation here at SITC very shortly with preclinical data, updated data for that allo mesothelin program. So that will be a poster presented at SITC and then we are very much on track with the IND filing in the second half of next year. And I will say, you know, as with any IND, you have to get all of your studies ready for the IND filing including of course for this type of therapy, the manufacturing aspects with this type of program. But I will say everything is moving ahead, very well with our partner Bayer here and again preceding that will be the IND filing for 3219 which is or allogeneic CD19 CAR T, which we think could be best-in-class and again we're targeting a Q1 IND of next year.
Pascal Touchon: There so maybe two additional point, we are very excited about this program. And so to 3271 in particular one aspect that is very unique to - in fact two aspects. First one is this 3271 is going to be made is being made right now in stirred-tank bioreactor that's a big first for an allogeneic CAR T or CAR T in general there. And I think that's why it's taking the time to put that together because that's a big first, but we have already evidence at some early stage that we can make this allogeneic CAR T into stirred-tank bioreactor which is growing, we believe, to change radically the manufacturing efficiency of allogeneic cell therapy manufacturing. So what's the pace there. The other aspect is the fact that we are maintaining TCR in 3271 we’re maintaining the EBV TCR there in our manufacturing process. We believe that's very important not only from a safety point of view as a recent example have been shown. But also we believe from an efficacy point of view. In fact, recently a clinical study has been published in Nigeria using mesothelin CAR T cells that edited to lose TCR PD-1 expression and what was very interesting in the Phase 1 study, that the others could not detect CAR T cells in 12 of the 15 patients. And the only three patients after just a few weeks and the only three patients in which we could detect where the patient for which they were in fact I think a few TCR that we're not gene editing. And they were TCR positive CAR T cells that were present there. So for us is a clear evidence that if you maintain the TCR you have more persistent if you delete the TCR all you modify the TCR for allogeneic CAR Ts for gene editing not only create a risk in terms of having additional gene addition in terms of safety. But you also a limit the CAR T that will stay only for few weeks, does it answer your question.
Operator: And our next question comes from Phil Nadeau from Cowen. Go ahead, Phil.
Phil Nadeau: Let me add my congratulations on real data. A few questions for from us on tab-cel - guess first on the guidance for Q2 FDA filing and I'm curious how confident are you that you can complete the BLA in Q2. It does seem like the FDA and the CMC division in particular are dealing with cell therapies is kind of evolving its requirements on the fly so appreciate that you have alignment. How confident are you that you know exactly what the FDA wants and that there is not going to be a newer request when you talk to the agency in Q1.
Pascal Touchon: Thank you, Phil I'll start and Jakob will chim in. I mean first of all, I like to say we are very confident that we are ready to file, I mean as I said we are filing in the next few days in Europe and so we have a full file ready to go and on all aspects of this product. We believe we have invested and develop a product that is of high quality and we've great data there and we're going to file in Europe in the next few days. Now in terms of the U.S. and the FDA discussion I mean, it's true that the, it's a step-wise type of a process. So far, we have a lot of questions coming there and there is a lot of data also that we could do that. I mean we are discussing think that they often are more the BLA review level and we're doing that in value study meeting that we have increased with the team and we are making progress step-wise progress there. So we certainly are understandings their questions and we're going to put together this new analyses they are asking for. And all the interactions with them, we cannot predict whether they will have ask other question, but we think we have given them all the data that that exists on the product and it's really around new analyses more than trying to create new data at this stage. Jakob, anything to add.
Jakob Dupont: Yes, and just to maybe amplify that as well. I do think as you see, we're making this step-wise progress. So, at the last quarterly call, we announced that we've got this clarity in agreement that the FDA wanted to see all of the lots that were manufactured in order to make this determination of comparability between pivotal and commercial material and the great news is we can do that. We have all those lots. So that was great clarity to get from the agency and at this quarterly call, we can now announce that we've made further step-wise progress with that October Type B meeting where we've now come to agreement with the FDA on comparability approach, including the statistical methodology. So again, this was an area of much discussion and we came to agreement there and then the agency have now further focus and said they want additional analysis on certain data points here, which we now providing to them in advance of our next interaction with the agency in Q1 of next year. So again, I think there is clear evidence of progress here and I think we are confident in that progress and Pascal says, it's really incredible as a pretty small company here that we are completing our first regulatory filing and submitting in Europe here as Pascal mentioned within the next couple of days. But the implications of that, is that we have a full regulatory filing that's been completed and we can leverage all of those documents. All of those analyses and all of that data in the BLA filing so we're really ready to go and so we've also of course shared clinical data with the FDA from the ALLELE study any other supportive studies as well and gotten guidance from the FDA in that clinical feedback that actually helps us to position the data in the BLA filing the type of information that you would get in a pre-BLA meeting. So again I think very nice progress here. And again very proud of the team here at Atara that's worked so hard on getting this regulatory filing together.
Phil Nadeau: And maybe a follow-up to your second point there in the past management suggested that if you thought you had perfect clarity on what was necessary for the FDA filing, you might be able to progress to the filing without a pre-BLA meeting. Today, it sounds like you think you need a pre-BLA meeting. So I guess we’re curious, what do you expect to learn at the pre-BLA meeting that you haven't already established from all the other Type B meetings that you've had?
Pascal Touchon: Yes maybe I can answer that one. I think it's really a step-wise aspect there that we need to have that final agreement on the comparability and that will lead also to the content of the model free. And then the pre-BLA will be just to align on the different aspects of the file in terms of content, because as we said, we have the file ready to go EMA. But FDA is asking some different type of analysis and so on. So want to make sure that the way we put together the file or we plan to put together the file for the BLA is aligned with the FDA there. So that's why a pre-BLA meeting, we believe and we discuss that with them will be, necessary more what I would call maybe the administrative part, which is to make sure that the way we put the data together that we have is aligned with their expectations.
Phil Nadeau: Perfect. And then last question from us is on to 3219. It sounds like the IND is on track for first quarter of next year. How long do you think it will take from the IND to actually dosing the first patient, I think in for prior CAR T therapies that there was somewhat of a lag maybe six months or so will that apply to 3219 or is it possible that you could dose a patient sooner than that?
Pascal Touchon: Yes, we're not going to comment on that Phil at this stage. So we will do that comment at a later stage when we are reaching that point. But suffice to say that we are trying to get all the learnings we can and with a lot of expense in the company about total CAR T and CD19 CAR T about the best way to accelerate the timing from IND to first patient and to make sure that we have the right type of patient that study is there. So we're working on that activity as we speak, but sorry, but we cannot give details is too early for that.
Operator: And our next question comes from Jonathan Miller from Evercore. Go ahead.
Jonathan Miller: Thanks guys for taking my question. One on one of the 188, I thought the MTR data you shared ACTRIMS is very interesting and obviously went through it again, a little bit on the call today. But I understand that MTR declines are associated with clinical decline in MS broadly, but has the inverse ever been demonstrated, I mean that is - has MCR stabilization but associated with disease stabilization or MCR increase associated with disease improvement. How much confidence do we have in this biomarker sort of being predictive in both directions I guess is my question there?
Pascal Touchon: Yes, no thank you very much for your question. AJ, do you want to take that one.
AJ Joshi: Sure, yes thanks for the question. I think the best way to look at it is this biomarker has been most utilized in the relapsing remitting space when you're looking at trying to make those correlations and when you're thinking about the disability improvement or resolution of symptoms in MS. Remember this is all about myelination right. So when you look at relapsing remitting lesions that are active. You will see MTR having significant decline. I shouldn't say substantial decline and then when those lesions resolve. You will see the MTR increase that by definition that the disability that's associated with that lesion is getting better, right. So in RMS there has been connections between MTR increase and presumably remyelination there and improvement in the clinical status of those patients. In progressive MS as you know, no has ever seem disability improvement and that's why to the questions you've asked. It's not been shown in progressive MS, as you see evidence of the MTR utilization for improvement in disability in RMS just hasn't been seen in progressive and that's why the data that we have are so unique. Because if you take a look at it for example, in the chronic T2 lesions where they're generally considered very old and many of those lesions we consider almost dead lesions. Those lesions are where we're seeing statistically significant remyelination and really importantly that's associated when you see the remyelination the patients who having that remyelination are the ones who had disability improvement. So this is the first time that people are seeing that in progressive MS. And this is why the data are so important because hints of it and relapsing remitting, but here, we're showing something really powerful in the progressive MS.
Jonathan Miller: And thanks, so much that makes a lot of sense. So I guess one more on and that's franchise. Just following up on the color you gave to Salim earlier in the call. When you talk about maintaining the integrity of the study, obviously the – even a smaller part of the study here is randomized, double-blind, are we to assume that the blinding is going to be maintained throughout the interim analysis? And therefore, the amount of data that you actually have in-house is going to be limited by what the prespecified DSMB run analysis provides you with like you're not, you're not going to have a bunch of data that you're hiring from us. It is more about the maintaining the blind in the study and a limited amount of data being pulled out of the IA is that's fair?
Pascal Touchon: AJ will start and I’ll chime in.
AJ Joshi: Sure, I think the best way to look at it is, we are, as you might imagine for any really robust randomized controlled trial work putting in as many controls as possible to make sure we maintain a stronger blind as possible. So of course the DSMB the safety monitoring committee will see all those at the data monitoring committee will see all the data. There'll be very limited exposure to the data internally. So it's not like we're looking to hide any specific information. But again, the best way to look at is, this will be conducted robustly. So we maintain the blind as much as we can so that way. The power of the result at the end will be a strong as we can.
Pascal Touchon: Yes and again, Jon I think, as we say the specifics of what we can say are going to be clarified at the time of the IA, because that depends very much from the data. That depends very much on the status of best of the following discussion with the FDA. Could it be the trans-communication of I mean, there are many valuables there. What we can confirm today is that these are not only will be very important milestone, but we'll be able to say while preserving the integrity of the study to say, not only what we are deciding based on that, but why we decided to a certain extent in terms of detail.
Jonathan Miller: Thanks so much Pascal it make sense. Maybe switching gears for just a second to 2271, looking forward to seeing some of that early data at ESMO IO just to expand on what you said previously, there I understand this is from the lower dose cohorts. But can you tell us how many patients in total. You're going to have there and whether we should expect meaningful dose response to continue beyond these cohorts we see it as ESMO IO?
Pascal Touchon: Yes, I think we are not commenting at this stage on the many patients and so on. You will have to wait for few weeks there we’ll give you details at the time, but we said last time that it was really the lowest dose cohort. So on the cohort one and 2 only. So these are I mean step-wise. Remember it was 1 million per for key for cohort 1 per kick cohort 2 and these are the low dose there. So that's why we are really focusing on safety and transnational there. I think that for us one of the key aspects will be really the PK because I mean we seen data from this type of CAR T and that are showing expansion. And then the CAR T starts to exhaust, and there is no more CAR T or at least much lower level there and if we could be able to see something different there but we’ll really be some proof of concept for having 1XX and as a costimulatory domain and PD1 DNR both of them having a role to play on persistence and we see difference mechanism against immunosuppressive so I think that could be great if we could show that.
Operator: And our next question comes from Salveen Richter from Goldman Sachs. Go ahead Salveen.
Unidentified Analyst: Thank you for taking the question. This is Tommy on for Salveen. Can you just remind us of the key points of differentiation on the tariffs mesothelin targeting CAR Ts compared to other competitors? Thank you.
Pascal Touchon: Yes Jakob do you want to take that one.
Jakob Dupont: Yes sure absolutely. So for our mesothelin CAR T just a reminder that this is a program that we partnered with Bayer and there are two programs in the franchise. There is the autologous program 2271, which is currently in the clinic, and that is the ESMO IO presentation that's going to occur here in December. And then there is the 3271 program, which is the allogeneic program where we're heading towards an IND filing in the second half of next year. So firstly what both of these programs have in common is the binder against mesothelin. So this is a binder that's already been derisked by an academic first generation program at Memorial Sloan-Kettering. So we know from the first gen program that this is a safe binder and again we'll share data here coming at the end of this year at ESMO IO. Additionally, what we have in our programs are 1XX costimulatory domain. So this is next generation costimulatory domain developed by Dr Michel Sadelain at Memorial Sloan-Kettering, where the idea is to innovate co-stimulation in the T-cells, so that you enhance in vivo expansion persistence and reduce exhaustion of those cells. So again this is an important costimulatory domain. Additionally, both programs also have PD1 dominant negative receptor constructed into the cells, where you do not - where the cells are not at risk for the tumor suppression from tumor PD L1 expression. And so again this is a unique feature that could also enhance in vivo persistence and prevent exhaustion as well. And so, the additional feature with the allogeneic program is that we're using our EBV allogeneic EBV T-cells as the cellular foundation for that those allo CAR T. And I think what's really important here is that we have a lot of clinical experience as we mentioned today nearly 400 patients treated with our EBV allo T cell platform they had - these cells have a great performance in patients. A great safety profile and importantly, we retain the intrinsic T cell receptor in those our allo EBV T-cells, and that's really important because as Pascal also mentioned a few minutes ago that those programs where you knock out the T cell receptor with CRISPR Cas9 you're actually really limiting the function of those T cells in vivo and yes, there's this evidence from the German publication in blood from a few months ago that shows that if you knock out the intrinsic T cell receptor the persistence of those cells. The in vivo side so toxicity of those cells and the performance of those cells is not as good as if you retain the intrinsic T cell receptor. And I will say. Another important feature and probably really critical here is that we do not do gene editing in our approach. We know the gene editing can have safety liabilities and issues we do not do gene editing in our CAR T programs. And so we think that that could also be a differentiating factor for us as well. Pascal anything further?
Pascal Touchon: No, I think you called all the aspect there and it's a very unique and differentiated platform there and also I think not only on the sort burden allogeneic following very fast. It's very exciting indeed.
Operator: Our last question comes from Yigal Nochomovitz, I'm sorry I can't pronounce your last name, Nochomovitz Yigal.
Yigal Nochomovitz: Hi, no worries. Hi Pascal and team. Thanks for taking the questions. Just curious, are there scenarios where at the interim analysis for ATA188. The study could either be stopped for either overwhelming efficacy or futility or is the interim analysis necessarily going to result in the sample size adjustment with the study continuing?
Pascal Touchon: Yes thank you for your question AJ?
AJ Joshi: Yes, there is - as with any other kind of robust interim you got week. There's always a possibility that you would on highly unlikely event that these stock for utility. And our intent would not, there's always a possibility that you start. We've an amazing efficacy round. So it's a standard interim analysis where you have those possibilities, but the primary intent really here is adjustment in sample size that would be our expectation.
Yigal Nochomovitz: Okay. And then just a separate question, when are we going to get an update on the Match trial and where would this be presented?
Pascal Touchon: I think we don't have the Match trial anymore. When we merger two trial that became the ALLELE, so ALLELE is now the pivotal study when we merge few number about not three years ago. We merged that into one study only one pivotal study only I think both SOT and HCT got.
Operator: And no further questions at this time.
Pascal Touchon: Thank you.
Operator: At this time, the conference has now concluded. We appreciate your attendance. You may now disconnect your lines and have a wonderful day.
