Atara Biotherapeutics (NASDAQ:ATRA) Q2 2021 Earnings Call

0:00 Good afternoon, everyone. Thank you for standing by and welcome to the Atara Biotherapeutics second quarter 2021 financial results conference call. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. Please be advised that today's call is being recorded. I now would like to hand the call over to Eric Heilengrand, Vice President of Investor Relations and Finance at Atara Biotherapeutics. Please go ahead, sir.

0:35 Thank you, operator. Good afternoon, everyone, and welcome to Atara's second quarter 2021 results conference call. Earlier today, we issued a press release announcing our second 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 Tuchon, President and Chief Executive Officer, Dr. Jacob DuPont, Executive Vice President and Global Head of Research and Development, Upal Kopikar, Chief Financial Officer, Joe Newell, Chief Operations Officer, Dr. Jose Vidal, Head of GMP Quality and Process Sciences, Dr. A.J. Joshi, Chief Medical Officer, and Dr.

1:36 Kristen Urema, Chief Commercial Officer. We will begin with prepared comments from Pascal and Jacob, 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?

2:20 Thank you, Eric, and thank you all for joining us this afternoon. We have completed a strong first half of 2021 and are making good progress on all three of our strategic priorities, TAP-Cell, ATA-188 in multiple sclerosis, and our next-generation allogeneic CAR-T programs. Supported by our breakthrough therapy designation, we have been having regular dialogue since January with the FDA. We recently conducted productive meetings with the review team at the FDA and gained alignment, clarity, and actionable next steps in order to submit the TAP-Cell BLA. First, we gained alignment with the FDA on the key methodology for evaluating comparability between TAP-Cell clinical and commercial products. In addition, the FDA asked for and we will provide to them data on substantially all TAP cell lots made to date by ATARA.

3:25 We believe this should clear the way for the FDA to make a determination at an upcoming Type B CMC meeting regarding our expanded data package supporting comparability between the product used in the pivotal clinical study and the intended commercial product. Next, the FDA decided It cannot make a determination of comparability between the non-pivotal product and the pivotal clinical study product. Hence, clinical data from the historical non-pivotal study will not be pooled with the pivotal allele study data. Rather, we intend to present these data in parallel as part of the BLA submission.

4:12 Importantly, at this time, The FDA has made no new request of ATARA to conduct additional clinical studies, develop new assays, or conduct new manufacturing of lots. We are confident that we will have a robust data package to demonstrate comparability to the FDA between pivotal and commercial process versions of TAP cells, and we are encouraged by the ongoing interactions as we work towards finalizing of CMC module 3 for the DLA submission. Turning to the pivotal allele study, we have recently successfully completed the analysis of the Q2 data cut previously requested by the FDA. Top line data shows strong objective response rate in line with prior results and a consistent safety profile with no new safety signals.

5:04 In addition, we now have new robust durability data as well. These data from a pivotal study are impressive. for such an ultra-rare and iron-methanate conditions like relapsed refractory PTLD where patients have no treatment options. The latest data cut will be discussed with the FDA for the Type B clinical meeting and is what we plan to use as the basis of both the BLA and the MAA submissions. As a reminder, we continue to plan to present these phase III allele data at an appropriate congress in Q4 2021. Looking ahead, we now have clarity around the required next steps for resolution and submission of the BLA for TAP cells.

5:52 Although this has taken some time, as ATARA is a trailblazer for allogenic cell therapy in the world and is paving the way for this first-ever allogenic, off-the-shelf T-cell therapy to reach regulatory findings, we now expect to complete the BLA submission for TAP cells in Q1 2022. Our investment in U.S. commercial readiness activities have been shifted to this new timing, gating or spending versus what was previously anticipated, as we now plan for TAP cell approval and U.S. launch in the second half of 2022. As we continue to prepare for commercial launch, I am very pleased to announce that cell therapy and oncology commercialization veteran Amit Malik was appointed to the Board of Directors.

6:42 Amit brings to ATARA's board a wealth of experience with U.S. payers, access, and reimbursement strategies, and launches of innovative oncology therapy, including CAR T's. Now turning to Europe, where we're also making excellent progress. We recently had successful pre-submission, as well as co-rapporteur and rapporteur meeting with EMA, and cleared all compliance checks. So we can now move forward to submit the EU market authorization application, for patients with EBV-positive PTLD in November of 2021. In parallel, there is a strong level of interest from ex-US partners, and our partnering discussions are progressing very well, in line with our expectations to secure a partner for Europe by Q4 2021. Meanwhile, we are also actively enrolling patients in our TAP-cell Phase II multicore study in other EBV-driven cancers.

7:40 The six study populations, of which the largest two are EBV-positive AID-LPD and EBV-positive PID-LPD, may support meaningful label expansion beyond second-line PTLD. Turning now to 8E188, our transformative product candidate for patients with multiple sclerosis. I'm very excited to announce that important new data will be presented in October at ECTRIMS. These will include new magnetization transfer ratio imaging data, an imaging biomarker linked with myelination, in addition to the two-year clinical data update from the Phase Ia open-label extension study.

8:25 We are excited to present this new data, and Jacob will have more to say in a moment. Meanwhile, we continue to make progress in enrolling the Phase II randomized double-blind placebo-controlled study, or NBOLD study. We are on track. to conduct an interim analysis of this study in the first half of 2022, including efficacy and safety in patients with progressive forms of MS. Following this interim analysis, we expect to have further discussion with the FDA regarding potential study adjustment for pivotal intent. These are important discussions from both regulatory and strategic perspectives for the program and could provide optionality on how we advance development.

9:12 Momentum, meanwhile, continues to build in the community, reinforcing the association between EBV, Epstein-Barr virus, and MS, and the transformative potential of 8188 for MS patients. This was confirmed by a recent survey amongst top US neurologists. We also continue to see significant interest from a number of large companies regarding a potential collaboration involving 8188, as we truly have a unique asset. the only investigational therapy in a randomized controlled trial in progressive MS with disability improvement as the primary endpoint. Moving to our CAR-T portfolio and first our mesothelin franchise program, ATA 2271 and ATA 3271, these mesothelin-targeted CAR-T products are benefiting from our global strategic collaboration with Bayer, which is off to a strong start.

10:10 For ATA2271, our autologous mesothelin CAR-T program, we expect to present the first update on Phase I data for patients with advanced mesothelioma in Q4 2021. The off-the-shelf, allogeneic version of this mesothelin CAR-T program, ATA3271, using a PD-1 dominant negative receptor and 1XX CAR co-simulatory signaling domain built on our EBV T-cell platform, is currently in IND-enabling studies and is progressing well. We expect Bayer to submit an IND in the second half of 2022 and subsequently lead clinical development and commercialization activities. Turning to ATA3219 or allogenic CD19 targeted CAR-T for patients with B-cell malignancies, we plan to submit an IND in Q1 2022 in line with our strategic goal to develop this asset as best-in-class for B-cell malignancies.

11:10 Moving to our financials, with regard to our cash positions and runway, our cash burn in Q2 was $61.8 million, and we ended the second quarter of 2021 with $373.4 million in cash. With this cash balance and our updated and well-controlled plan-expand profile, we believe we are sufficiently funded into 2023. As we turn ahead into the third quarter of 2021, I am delighted to see how far ATARA has come from this time a year ago. Each and every one of our staff has delivered on our goal of saving and improving lives of patients with serious disease. On a daily basis, we partner closely with clinical study sites, with our manufacturing and logistics partners, and our collaborators, in order to ensure patients could continue to access our therapies.

12:06 With the hard work of the ATARA team, We are on a clear path to file our TAB-CEL regulatory submissions and bring this life-saving medicine to patients in need. I will now turn the call over to Jacob. Jacob?

12:19 Thank you, Pascal. I am pleased to provide further details on the progress we made during the second quarter in advancing our three strategic priorities. Starting with TAB-CEL, we have aligned with the FDA on several key aspects required for BLA submission. Regarding comparability of TAB cell clinical and commercial product, we reached alignment on methodologies for evaluating these two sets of products. As requested by FDA, we are providing data on nearly all pivotal and commercial TAB cell lots manufactured to date. We believe FDA should agree on our comparability data package when we discuss these new data at an upcoming Type B CMC meeting. This belief is directly related to the consistent and tightened process performance data that was generated from the pivotal and commercial production campaigns, as well as the fact that process changes between pivotal and commercial were minimal and mainly related to the commercial GMP compliance of the EBV viral reagent used in manufacturing.

13:34 With regard to comparability of historical non-pivotal TAB cell product versus pivotal clinical study product, the agency recently clarified that they would like to see comprehensive analytical data on most historical lots. Therefore, we have agreed with the FDA that comparability cannot be established because we do not have product available for some of the lots manufactured by MSK in the past. This important resolution of comparability means that clinical data generated using historical non-pivotal product will not be pooled with pivotal clinical data. Importantly, this decision is consistent with a prior FDA decision to evaluate in parallel the data of a CAR T product from an academic center's non-pivotal product versus the industry partner's pivotal clinical study product. for which ultimately the FDA granted marketing approval.

14:38 Turning to the pivotal allele study, we have recently successfully completed the analysis of the Q2 data cut requested by the FDA for the phase three allele pivotal study. Top line data evaluated through independent oncologic and radiographic assessment shows Strong ORR in line with prior results with half the patients responding and a safety profile consistent with previously published data with no new safety signals. Importantly, this new data cut demonstrates new robust durability of response. This latest data cut is what we plan to use as the basis for both the BLA and the MAA submissions. while also providing additional supportive data from our historical non-pivotal studies, expanded access, and compassionate use study patients.

15:39 To summarize next steps, we anticipate speaking with the FDA in a Type B CMC meeting to discuss our expanded data package on comparability between pivotal clinical study product and commercial product as well as a Type B clinical meeting to discuss the latest data cut from the allele study now with robust durability of response data requested by the agency that will form the basis of the BLA filing. Requests to FDA for these meetings have already been made and pending alignment, we could then file the BLA in the first quarter of 2022. As Pascal mentioned, we've also made excellent progress in Europe.

16:25 TabCell's prime and orphan drug designation with EMA has enabled regular engagements with the agency and our PIP compliance checks have been successfully cleared. Our recent successful pre-submission as well as co-rapporteur-rapporteur meetings means that we have cleared the path for the MAA submission in the EU. Therefore, we can submit the market authorization application for patients with EBV-positive PTLD in November of 2021. Taking a step back and thinking about PTLD patients in dire need of treatment options, we recently joined the Rare Disease Company Coalition alongside other rare disease leaders and constituents to engage in conversation with policymakers on the need for speed and access for life-changing therapies.

17:20 Atara is committed to leading the path forward for transformational therapies for rare disease patients. Moving now to ATA-188, our product candidate for progressive multiple sclerosis. We are excited and look forward to presenting at ECTRIMS in October long-term two-year clinical data from the Phase I open label extension and new translational data from the Phase I study of ATA-188 and progressive MS. Included will be new imaging biomarker data considered to reflect the state of myelination in the CMS known as magnetization transfer ratio, or MTR. With respect to MTR, decreased MTR in MS lesions may correlate with demyelination and axonal loss in MS patients, while increased MTR may correlate with remyelination, These data may provide key information on the mechanism of EDSS improvement in our ATA-188 clinical data. We are excited to present these new data in October. We also plan to use MTR as a relevant imaging biomarker correlated with disability improvement in our ongoing Phase II EMBOLD study. Turning now to our CAR T programs. In addition to Pascal's comments, I would also add that we are making excellent progress

18:51 on our mesothelium franchise programs with our partner Bayer. This partnership is helping to demonstrate the progress of the technical and manufacturing elements of our EBV T-cell platform. We are delighted to leverage the capabilities of such an experienced company as Bayer and look forward to providing further updates later this year. ATA3219, our allergenic CAR T for patients with B-cell malignancies is also advancing well and we believe that this therapy could be a best-in-class treatment in B-cell malignancies as there is still significant unmet need despite increased therapeutic options.

19:36 Finally, I'd like to extend a warm welcome to our newest leadership team member, Chief Scientific Officer, Dr. Koki Nguyen. Koki comes to us most frequently or most recently from fate and brings his deep experience in CAR-T paired together with a strong conviction around the unique benefits of our EBV platform to drive our exciting CAR-T cell franchise forward into the future. I'll now turn the call back to the operator to begin the QA portion of the call. Operator? At this time, we'll be conducting a question and answer session If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation symbol indicates your line is in the question queue.

20:24 You may press star 2 to remove your question from the queue. For participants using speaker equipment, it may be necessary for you to pick up your handset before pressing the star keys. One moment while we poll for questions. Our first question comes from the line of John Newman with Canaccord Genuity. You may proceed with your question.

20:46 Hi there. Thanks for taking my question. And congrats on the good progress here. Jacob, you mentioned the submission has been made, the request for a Type B meeting for the comparability data for TAP cells. Just curious if you know about when that might take place. And then on the clinical side, Beyond the most recent data look for allele that you've conducted, I'm just curious if you think the agency will require any additional data looks in the future, maybe either with some additional patients or longer follow-up. Thanks.

21:27 Thank you, John, for your question. Jacob, do you want to take the first one?

21:31 Yeah, thanks, Pascal, and thank you, John. So yes, we have submitted meeting requests for the Type B meetings, both for CMC comparability and for the clinical discussion as well. Now, per PDUFA timelines, we should hear back from the agency within 60 days of that request. So we believe that this meeting will occur within the next two months.

21:59 And the second question on clinical data beyond allele. Yes, absolutely.

22:03 So we believe that this new analysis for allele is strong enough to support a BLA filing. But of course, if the FDA wants updates specifically such as safety with a subsequent 90-day safety cut, we can certainly do that. But we do believe that the current Q2 data cut for allele is sufficient to support the BLA submission as well as the MAA application. And as you know, we're also going to be providing historical non-pivotal data and EAP and SPU clinical data in the BLA and MAA filings in parallel, but not in a pooled fashion due to the outcome which we thought was quite favorable in terms of non-comparability between historical and pivotal material.

23:01 Does it answer your question, John?

23:04 Yes, it does. Thank you.

23:06 Thank you. Our next question comes from the line of Jonathan Miller with Evercore ISI. You may proceed with your question.

23:17 Hey, guys. Thanks for taking my question. Congrats on all the progress. It does seem like the FDA is being pretty cautious on this Abcel DLA. I guess given that you can't pool and that you think the Q2 update on allele is as far as you're going to need to go, what is the duration of response that you'll be able to claim on the pivotal data relative to what you could have claimed on the pooled data? Separately, it seems like IND timelines for the allogeneic CAR-T programs are going to be a little bit towards the back end of the prior guidance. I just wondered, what's the gating factor on those INDs going forward from here?

23:59 Thank you for your question. Do you want to take the first question, Jacob, please?

24:03 Yes, absolutely. I would say that we've made great progress with the FDA in terms of understanding the comparability issues and then obviously also providing this Q2 data cut that the FDA requested from us in October of last year, specifically to provide durability data on the patients that had already enrolled. Now, the guidance that the FDA has provided to us, which they provide to other sponsors, is that they want to see durability of that response, which basically means that from the time that a response is detected, you want an additional six months of follow-up on those patients since the time of response. So if you think about, we got that guidance in October of last year.

24:50 We let the data mature further, collected the data based on a Q2 data cut, then provided it to our independent review facility for independent oncologic and radiographic response. It really fits those criteria of six months duration of response after that initial response is detected, and that's pretty standard requests from the agency.

25:15 Yeah, and I think the fact that we align with the agency on the durability of response we want to see, and we have this data now, makes us very confident in the strength of this data package that we'll present in a forthcoming Type B clinical meeting. So on your second question, It's just that we have refined our thinking on the different manufacturing timelines for this program and developments that is needed to file the IND. The work we are doing on this platform as we progress on these specific programs will, by the way, help the rest of the early pipeline. And we are leveraging our platform there. So there is no particular aspect there that is a particular challenge, apart from the fact that we have now fine-tuned the exact timing for the IND filing and for ATA3219 it will be of course ATARA filing the IND whereas for ATA3271 it will be Biotherapeutics filing the IND there.

26:08 Now we're also trying in developing this IND package to make sure that we can optimize our chance of having a true best-in-class platform for allogenic CAR T and this is we believe where ATA3219 in particular could have significant potential advantage in optimizing characteristic of the cells to make sure that we can leverage the innate properties of EBVT cells together with 1XX as a costimulatory domain to really make something that could go to the clinic with the potential and the goal to be a best-in-class in B-cell malignancies. Does it answer your question, John?

26:47 Yes, absolutely. Thank you. Our next question comes from the line of Salim Saeed with MeSchool Securities. You may proceed with your question.

27:00 Great. Good afternoon, guys, and congrats on the progress. A couple from me, if I can, on ATA-188. So Pascal, you sound pretty excited. And I know the press release even uses that word, exciting new imaging data. So as much as you can say here about the MTR and whether this actually refers to myelination patterns, are you seeing or you think you're seeing remyelination with ATA-188. I'm curious to get your thoughts on the FDA being able to use this as a biomarker for accelerated approval, just given everything we've seen with the accelerated approval around Alzheimer's. Thank you.

27:48 Thank you, Salim. We are definitely excited, but we are not going to give you the data that you'll have to wait for October. But AJ, do you want to comment on MTR and what we believe this particular set of data is very important and what's our plan with the FDA in terms of how this could be used as a biomarker?

28:08 Yeah. Thanks, Pascal. Hey, Salim. Yes, I think, you know, with the MTR data, you've heard that. It's pretty much the – when you look at MRI biomarkers looking at myelination, that's really the most used one in all the studies that you're looking at. And as you might imagine, you know, it's been correlated with decline in EDSS, so decline in disability. So, you know, if you have lower MTR, you actually have lower MTR means you have demyelination. That means you have a decline in disability. So that correlation has been made. What's interesting is no one's actually shown improvement because, as you know, no product has shown improvement in disability in a progressive situation. But what is interesting is if you take a look at MTR in relapsing disease, So this is where you've got an active lesion and you use a therapy that works in inflammatory disease, you'll actually see MTR increase because you get remyelination once the inflammation calms down.

29:08 So you do see MTR increasing when you have remyelination. It's just never been shown in the progressive setting. So from that standpoint, what we're trying to do is we're trying to say, look, MTR is relatively established as a measure of myelination, both demyelination and re-. and we're now trying to apply that to the study data that we have now. So obviously we're looking forward to presenting the data coming in October. And in terms of how you could leverage this going forward, it's really not been used as anything like a surrogate marker or anything like that to date. But again, a lot of that we think is just because there hasn't been a lot of good reason to take a look at disability improvement and MTR changes. We're going to very closely monitor MTR throughout the course of the EMBOLD study. And we're going to be talking to FDA, and we will be including all of the MTR discussions in those conversations. But today, it's a little bit too early to say, yes, this is going to be an established biomarker.

30:10 But from a scientific perspective and a clinical perspective, it is established within the scientific community right now.

30:17 Yeah, and as AJ has said, it will be one of the endpoints we'll be following in the current randomized control trials. So not only we have data coming in October on the phase one, but we'll have also data coming forward later on on the phase two study when we get access to this data. So that's something of a plan in terms of leveraging this particular biomarker that has been used in a number of studies, but not yet correlated with improvement in this ability, and that could be something very exciting.

30:51 Super helpful. Thanks so much. Our next question comes from the line of Phil Naju with Cowan. You may proceed with your question.

31:01 Good afternoon. Congrats on the progress and thanks for taking our question. A couple on the comparability issue. You mentioned briefly in your prepared remarks what the differences are between the pivotal and commercial material. Could you go into a bit more? And then, secondarily, now that the methodologies have been clearly defined, can you talk a bit more about your confidence that the FDA will find the pivotal and commercial material comparable? Thanks.

31:30 Now, certainly, Jose, do you want to address the first question on the difference between pivotal and commercial material? And then, Jacob, you can address the second question on the FDA, how we perceive the confidence that we have, that we have data that will be to decide positively on comparability.

31:49 Yes, the difference is the actual source and grade of the Epstein-Barr virus that we use in the manufacturing process. We switch from a clinical research grade producer cell line to produce the virus into a full GMP commercial grade producer cell line. and we switched also the manufacturing place of the virus to our own facility from the previous CMO as the CMO had no capacity to supply commercial volumes. We have done full characterization on that and we're pretty confident that it's a minimal change, but that's the summary of the change between the people and clinical material.

32:32 Thank you. And Jacob, how do we see the data package for the FDA?

32:36 Absolutely. I think one of the really important things, Phil, that we learned from the FDA is their thinking evolved around Tab-Cell, which is, as you know, the first allogeneic T-cell product, which is going across for FDA approval. We learned that they have this requirement now to see the data from all the lots that have created in order for a determination of comparability to be made between pivotal material and commercial material. That was the reason why we could not deem comparability between historical and pivotal because we simply didn't have some of the lots from Memorial Stone Catering.

33:22 But what we do have are virtually all of the lots from pivotal and commercial so that we can do full comparability analyses. having the agency give us the lay of the land and what the requirements were in terms of sharing the totality of that data, that is something that is really accomplishable from our perspective. And having that clarity from the agency is really valuable. So that's why we put the Type B meeting request in, which again will occur within the next 60 days or so. And we will put to them exactly that question of have we now secured this comparability with the full data package with the help of Jose and his full team in CMC manufacturing.

34:09 And we believe that we're going to achieve this because we know what the rules of engagement

34:15 are. Yeah, and we say also that the full data set we have is really very robust due to the robustness of our manufacturing process performance and the minimal changes that we've made between pivotal and commercial process, as Jose just explained.

34:32 Great. And maybe one last question.

34:34 Yeah, maybe just one last question. What's the rate-limiting factor to the Q1 filing? Is that completing the comparability analyses, or is there something else that's gaining?

34:45 Jacob? Yeah, so to provide these details, so as mentioned, we want to have the Type B CMC meeting within 60 days to solidify the issue of comparability of pivotal to historical, so that will get taken care of. then we have the Type B meeting for clinical where we share the most recent data cut from allele and we get the agency agreement on that. Now that hopefully is going to solve most of the issues. Now there may be some more administrative issues that could get taken care of in a pre-BLA meeting. So our base case is have these two Type B meetings with the FDA and then after that have a pre-BLA meeting that leads to a Q1 for the completion of the BLA filing. Now there is an outside chance that if we secure all the issues in these two Type B meetings that we may be able to have a faster submission of the BLA, but frankly our base case is to say we need to have these two Type B meetings, then the pre-BLA meeting, and then we complete the submission of the BLA.

35:52 And what makes us confident there is, again, the strength of the data. We know the data. in terms of clinical data there from the allele that I cut into too, and they're very strong. We know the robustness of our process, and we have all the data needed to provide the FDA with substantially all the data on all the lots made by ATARA. So in terms of delivering what the FDA is asking for, we feel very clear.

36:20 That's very helpful. Thanks for taking our questions. As a reminder, if you would like to ask a question, please press star one on your telephone keypad. One moment while we pull for questions. Our next question comes from the line of Matt Fitz with William Blair. You may proceed with your question.

36:42 Good afternoon. Thanks for taking my questions. I have a few. First, was it always the plan to have a Type B clinical meeting after the Q2 data cut? It just seems like that would kind of made it impossible to previously have hit your guidance for Q3 submission, completing that submission, regardless of obviously the CMC issues. So just wondering if that is something new, because again, it doesn't seem like that lines up with your previous guidance on timelines outside of obviously the CMC issues.

37:13 Okay, so maybe answer the first question on the guidance, and then you say that you have some other questions. Now, I think when we put the guidance on Q3, it was really based on the Type B CMC meeting that we had in Q2, and on the basis that following that Type B CMC meeting, we could then move from a pre-BLA meeting and in the August timeframe based on the data cut, and then go with that with the submission of the BLA by the end of the Q3. That was basically the guidance basis there. Now, what's happening is we have the two aspects now. We have the new data on the Allil dataset, and then we have at the same time the data coming from this request of the FDA that will have the need to see nearly all the manufactured load by Atara there.

38:10 So we align with the FDA during our recent interactions, and that was just a couple of weeks ago, where the best way forward will be to have in parallel a Type B meeting on the CMC aspect, a Type B meeting on the clinical, so you can look at the clinical data there, and then we can have a pre-BLA that will just be the more check-the-box administrative part of the pre-BLA meeting. So that's why it's put together with these two Type B meetings and then a pre-BLA. and in the past it was supposed to be the move directly from the Type B CMC to a Pre-BLA. Jacob, anything to add to that?

38:43 No, I think that you've summed it up very well, Pascal.

38:47 Does it answer your question, Matt?

38:50 Yeah, I guess so. It just seems like maybe there's something that's come up that's required another Type B meeting since that obviously wasn't planned originally, but okay. Just wondering, you previously said that you had about 15 lots manufactured from Comparability. I wonder if that's still kind of the number you plan to go into this Type B meeting with on the CMC side, or if there's any additional lots that will be used in the Comparability.

39:14 Maybe Jacob, you want to start, and Jose can chime in if needed.

39:18 Yeah, absolutely. So, Matt, I think this really speaks to how the thinking of the FDA has evolved in and where we now have this clarity of guidance because, you know, you're right. What we presented to the agency was 15 lots from each process version, which really gives us robust statistical power for that comparison. Now, for example, if you talk about a small molecule inhibitor or you talk about an antibody, generally speaking, they want about, you know, three lots to compare statistics on that. We're providing 15 of each processed version, but then the agency came out and said, listen, we really want to assess all your lots for pivotal and commercial, which is really more consistent with the request that they made for Allocard T, because, I'm sorry, AutoCard T, I'm sorry, auto is what I'm referring to, where each one of those products, each one of those cell products was an individual drug for that individual patient. So the agency wanted to see every single one of those.

40:27 Now the whole idea with allogeneic T-cell therapy is that you're able to treat many patients from your inventory, so you don't need to make one product from each patient. So we have proposed this robust statistical approach where we gave them 15 lots from each of the process versions. But the agency did fall back to this approach with us and said, we want to see all lots. And we said, okay, fine. We can deliver that with our pivotal to commercial material. And that's exactly what we're providing to them in this Type B CMC meeting, which is where we have confidence that we're going to be able to resolve this comparability issue.

41:12 Jose, anything to add to that? Yes, to the question of beyond the 15 lots per process version, in total we're presenting now 74 lots to the agency.

41:27 Okay. That represents more than 95% of the total lots produced, so that's exactly what the agency wants to see. And we believe that the main rationale is that they want to confirmed the robustness of manufacturing process for cell therapy, and are they used to with autologous? You know, they have habits now.

41:50 Okay. One last question. On the magnetic transmission NTR data that we're going to see, is this something you've collected on every patient, or how many patients should we expect? Because I can't recall this being something that was listed as a data being collected, and just will it be – how many – Time points, is it a pre-treatment and then now a 12 or 18-month follow-up? Can you give us anything else on what to expect here?

42:20 AJ? Sure. So the way the MTR works is it's really an analysis you can do when you've got a good quality MRI done. So when you have a good quality MRI result, you can actually go ahead and do the MTR analysis at whatever time points. So as you know for our Phase I study, We did six-month and 12-month time points for EDSS, so that's the kind of thing we'll be looking to talk about with MTR. And then going forward in the RCT, literally every single time point that an MRI is done, we'll be able to assess the MTR as well.

42:57 And on the number of patients, that's all the patients in the Phase I?

43:00 All the patients that have a good MRI will have a result there, yeah. Okay, good.

43:05 That's in the Phase I, yeah.

43:07 Yeah. Our last question comes from the line of Ben Burnett with Stiefel. You may proceed with your question.

43:18 Hi, this is Kaylee Breeze on for Ben Burnett. Thanks for taking our questions. We just have two kind of quick ones. I was wondering if you guys could give any additional color on what we might see at the ATA 2271 readout, the first one, in terms of maybe duration of response or the number of patients we might see. And then additionally, I'm wondering, I had a question for ATA3219, if you guys are planning on releasing any preclinical data for that.

43:55 Thank you. Thank you for your question.

43:57 Jacob, do you want to take these questions? Yeah, absolutely. So thank you for the question. In terms of ATA2271, which is our Autologous Mesothelin CAR T Program, which we're doing with Memorial Sloan Kettering. Obviously, it's in the Bayer partnership as well. As we've announced, we do plan on presenting the first clinical data at a relevant medical meeting before the end of this year. So we're certainly intending on presenting that clinical data. Now, we do plan on presenting safety, efficacy, biomarker data from the study.

44:44 And we have enrolled the first cohort of patients on the study with our partners at MSK. And we're currently enrolling the second cohort as well. So again, depending on data maturity and so forth, you'll see these various elements. And I do want to highlight This program, we think, is really quite innovative and interesting because, yes, it's autologous, and it has this 1XX co-stimulatory domain that we've been licensed from Michelle Satterlain and his team, which we think is a potentially best-in-class co-stimulatory domain for CAR-T. And it also has the PD-1 dominant negative receptor, which provides intrinsic overcoming of the immunosuppression of Tumor PD-L1.

45:35 So the auto program has both of these components. Now, obviously, we're working also on the allogeneic program 3271, and that's moving towards an ID filing, where at this point, we're leveraging our EBV T-cell platform additionally there. Now, in terms of ATA 3219, and we're very excited about that program. It's our first allogeneic Car T-cell program, Out of the Gate. It's directed against CD19. We do believe this is a best-in-class, potentially, program. And we did present at ASH last year in 2020 preclinical data from that 3219 program, so we can certainly – that data is certainly available from ASH.

46:28 and that also leverages this 1XX co-stimulatory domain from Dr. Sadlin and his team at MSK. And we're excited about that forthcoming IND submission.

46:42 Pascal, anything further? The only thing is to remind everyone that this program is also, we believe, supported by this clinical proof of principle that was established by the team at Memorial that show at the Congress in 2020 that a similar type of construct based on EBVT cells from healthy donors to which they have added CD19 CAR-T, in that case with a traditional co-stimulatory domain, then they treated patients with advanced B-cell malignancies and they achieved an 83% CR rate. And that study was quite amazing and unique in a sense that they followed patients for a very long time and that CR rate was maintained over a median follow-up of nearly two years. So I think that's really a very impressive data set, albeit on a small number of patients, but with long durability of response and excellent safety.

47:35 So that's a nice proof of principle for what we want to achieve there as a potential best-in-class, in particular having now 1XX as a cost-simulatory domain. Any further questions? That's it for me. Thank you.

47:57 You're most welcome. That concludes our question and answer session for today. Thank you for joining the Atara Biotherapeutics Second Quarter 2021 Financial Results Conference Call. You may disconnect your lines at this time.