Atara Biotherapeutics, Inc. (ATRA) Q1 2022 Earnings Report, Transcript and Summary

Good afternoon, everyone. Thank you for standing by, and welcome to the Atara Biotherapeutics’ First Quarter 2022 Financial Results Conference Call. [Operator Instructions] Please be advised that today's call is being recorded. I'd now like to hand the call over to Eric Hyllengren, Vice President of Investor Relations and Finance at Atara Biotherapeutics. Please proceed, sir.

Thank you, operator. Good afternoon, everyone, and welcome to Atara's First Quarter 2022 Results Conference Call. Earlier today, we issued a press release announcing our first quarter financial results and operational progress. This press release and an updated 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?

Thank you, Eric, and thank you all for joining us this afternoon. I would like to start with ATA188, our potentially transformative therapy for multiple sclerosis, where in the first quarter, we have made good progress and momentum continues to build around this exciting program. This recent momentum was marked by 2 landmark publication in Nature and Science, which continue to drive significant interest and awareness of EBV as the leading cause and trigger of MS in the medical, scientific and investment community. In addition, we conducted a successful EBV and MS Day in March, where we covered the MS disease landscape; the history of ATA188; an overview of EBV as a cause of MS; and very importantly, updated Phase I and open-label extension data, highlighting that a majority of patients have demonstrated either confirmed EDSS improvement or stability in up to 42 months follow-up. These events clearly establish ATA188 as a unique opportunity for value creation with its potential to transform patients' lives and the treatment paradigm in MS. Jakob will have more to say in a moment. Looking ahead, we are pleased to announce that we are on track to conduct the interim analysis of the Phase II EMBOLD study in June. As a reminder, the goals of conducting the IA are, first, to decide whether we should increase the sample size or not in order to achieve the target conditional power by the end of the study. Second, it will be used to inform Phase III timing, design, planning and investment. And lastly, it will inform broader development plans, including Phase II studies in potential new indications. Ultimately, the interim analysis data will allow us to accelerate and expand ATA188’s development from starting Phase III preparation, discussing further development steps with FDA and finding the right partner for value creation. Once we analyze the data and decide on sample size and timing for study completion, we plan to communicate both our decisions and the rationale behind our decision in July of this year. We then plan to discuss with the FDA the IA data and next steps for potential development pathways under ATA188 Fast Track designations for both nonactive primary progressive MS and nonactive secondary progressive MS. In parallel, we intend to accelerate our partnering discussion with biopharma companies that are progressing very well so far. Turning now to tab-cel. I would like to provide an update on our MAA in the EU and our continuing dialogue with FDA in the U.S. First, we are on track and continue to expect a decision regarding tab-cel European Commission approval in the fourth quarter of this year. As part of our ongoing dialogue with European Medicine Agency, EMA recently requested additional time to review our answers to their day 120 list of questions, which results in adding an additional 30 days to the review process. We believe the answers we are preparing for the EMA will sufficiently address their questions. As a result of their need for additional time, EMA transitions tab-cel to a standard assessment review time line. However, even after this transition to standard assessment, we continue to anticipate EC approval in Q4 of this year. Looking ahead, a key step in the regulatory review is conducting pre-approval inspections with EMA, and we are pleased to say that the dates for the pre-approval inspection have recently been confirmed. We are making good progress and are looking forward to completing this inspection with EMA soon. In addition, as we previously have noted, comparability data have been submitted to EMA through our MAA filing. We have now received the EMA Day 120 Critical Assessment Report, and EMA has considered the comparability data between clinical and commercial manufacturing process versions are sufficient to demonstrate comparability. We are pleased with our progress and look forward to further dialogue with EMA. On the U.S. regulatory front, we are actively discussing proposals to enable a potential filing of the BLA without conducting a new Phase III study. Specifically, our proposal leveraged tab-cel status as a BTD product, addressing an ultrarare and urgent medical need as patients in second-line PTLD has no approved therapy and a very limited median life expectancy of just a few weeks to a few months. We have made several proposals to the FDA. First, to use only commercial lots that meet a range of specification coming from our clinically used lots. Our extensive clinical data in more than 190 patients with EBV+ PTLD clearly establish, we believe, the safe and effective range of values for key product attributes, enabling determination of acceptable commercial product specifications. Second, we propose to use the clinical data being generated with the commercial product in current studies as a way to support a filing without an additional Phase III study. Lastly, we propose an appropriate monitoring of patients in a post-marketing setting. The FDA is reviewing our proposals, and we expect to provide further clarity on a potential BLA pathway in the next few months. I continue to feel confident that we will find a constructive way to get tab-cel filed and approved in the U.S. Moving to operational and financial updates. Last month, we welcomed Charlene Banard to Atara as Chief Technical Officer, overseeing process science, process development, quality, manufacturing and supply. We also successfully completed the sale of our manufacturing facility to FUJIFILM Diosynth Biotechnologies, or FDB, for $100 million at fund and began a partnership with FDB for access to flexible capacity to manufacture clinical- and commercial-stage allogeneic T cell therapy. The partnership is going very well, and the transaction is expected to reduce as our Atara planned operating expenses over the multiyear publishing period. With regard to our cash position and runway, we ended the first quarter of 2022 with approximately $302 million in cash. We believe cash as of March 31, 2022, plus the $100 million received from the closing of the strategic transaction with FDB in April will be sufficient to fund the company plant operations into the fourth quarter of 2023. I will now turn the call over to Jakob to give you more details on ATA188 development or CAR T programs. Jakob?

Thank you, Pascal. With regard to ATA188, as Pascal mentioned, momentum and awareness continues to build following the 2 landmark studies in Nature and Science identifying EBV as the leading cause and trigger of multiple sclerosis. ATA188 awareness has increased inphysician surveys conducted by Atara and by external parties as well. Of note, a longitudinal survey of a cohort of high-prescribing neurologists was conducted 6 weeks following the publication and showed 56% were in agreement that targeting EBV is a viable therapeutic strategy in multiple sclerosis. This was a threefold increase versus survey results from Q4 of last year, which was prior to the Nature and Science publications. During our recent EBV and MS Day, the momentum for this potentially transformative product continued to grow with a presentation of updated Phase I and open-label extension data that demonstrated that 33% of patients in the high-dose cohorts achieved confirmed EDSS improvement at the 12-month time point. And 20 out of 24 patients have had either confirmed EDSS improvement or EDSS stability throughout their observation in the study with up to 42 months of follow-up. Of note, one of our MS experts, Dr. Mark Friedman, commented that if ATA188 were to show 20% to 30% confirmed EDSS improvement in Phase II, we would have a game changer for patients. We are very excited about the potential for this therapy to help patients and are looking forward to the results of the EMBOLD study. Looking ahead, as we prepare for the Phase II EMBOLD interim analysis in June, I would like to remind everyone that the primary endpoint of this Phase II study is confirmed EDSS improvement at 12 months, which has been agreed to by the FDA. The IA will primarily focus on EDSS improvement at 6 months, which based on Phase I data was found to be greater than 85% predictive of achieving confirmed EDSS improvement at 12 months. This IA will include EDSS improvement beyond 6 months for patients with longer treatment duration and will also include other clinical endpoints and various biomarker data, such as magnetization transfer ratio, or MTR, and other biological biomarkers. Results of the IA will determine whether any sample size adjustments would be needed to achieve the target conditional power by the end of the study. The IA will also inform the best Phase III timing, design and planning and will inform broader development, including additional indications. As a reminder, our current target enrollment of 80 patients is expected soon after the conduct of the interim analysis. As Pascal mentioned, after we make the decision on sample size and steps forward, we plan to communicate both the decision and the rationale behind our decision to you in July. Turning now to our CAR T programs. I'd like to provide an update regarding our autologous mesothelin product candidate called ATA2271. This is being developed by our partner, Memorial Sloan Kettering Cancer Center and the recent series fatal adverse event in a patient treated in the ongoing Phase I MSK-conducted investigator-sponsored trial. Final autopsy results are pending, and additional studies are being conducted by MSK. Based on our assessment of the available information to date, we believe that the death is not caused by ATA2271. The final assessment and determination of causality will be made independently by MSK and communicated to the FDA in addition to any intended informed consent and/or protocol amendments. As a reminder, MSK voluntarily paused enrollment of new patients in the study. Additionally, for this program, Atara and MSK expect to provide a Phase I data update for ATA2271 in the second half of this year. IND-enabling work for ATA3271, a separate off-the-shelf allogeneic CAR T therapy targeting mesothelin using next-generation PD-1-dominant negative receptor and 1XX CAR T technologies for patients with advanced mesothelioma and other solid tumors, is advancing well with the IND filing anticipated in Q4 of this year through our partner, Bayer. Importantly, Atara's approach to CAR T does not require TCR or HLA gene editing and retains the endogenous T cell receptor. This has been shown in academic studies to increase persistence, durability and tracking of the CAR T cells. In addition, we are advancing the wholly Atara-owned ATA3219 program, a potentially best-in-class allogeneic CAR T, for B-cell malignancies expressing CD19. And we are on track to submit an IND in Q4 of this year as well. For ATA3219, we have implemented a targeted design and manufacturing approach in order to differentiate it from existing products through 3 essential factors. First, our approach maintains the endogenous TCR. Second, we are utilizing the 1XX co-stimulatory domain to prevent T cell exhaustion. And third, our manufacturing approach delivers a cellular phenotype that enriches for central memory T cells to enhance in vivo expansion and persistence without the need for extensive lymphodepletion. Given the data that has been presented thus far in the CD19 space, we believe that the ATA3219 program has the potential to be a best-in-class differentiated therapy based on the expected safety of the EBV CAR T cells, the potentially higher response rates and potentially longer duration of response as well as the off-the-shelf accessibility. We believe this could address a high unmet medical need for the approximately 60% of patients who do not achieve complete response at 6 months with existing CD19-directed CAR T cell therapy. Before I turn back to Pascal, I would like to extend my gratitude to Atara staff, our collaborators and the patients involved in our studies. Together, we hope to bring allogeneic T cell therapies to patients in need, some of these with curative potential. Back to you, Pascal.

Thank you, Jakob, and thank you all again for joining us this afternoon. Before we begin Q&A, I'd like to end my prepared remarks by saying this is truly an exciting time for Atara with our forthcoming interim analysis for ATA188, a unique potentially transformative therapy for MS. I am personally excited to achieve this key milestone in June, just in a few weeks, and look forward to communicating further with you in July. After which, we will discuss further with the FDA and with potential biopharma partners. As I look forward to these upcoming events, I would like to thank all staff at Atara for their hard work in creating value for patients and the company. I'll now turn the call back to the operator to begin the Q&A portion of the call. Operator?

[Operator Instructions] Our first question comes from Salim Syed with Mizuho.

Just a couple for me on ATA188, if I can. So Pascal, a lot of people around this IA seem to think that this is not going to be an interpretable readout. We're going to get a sample size adjustment and we're going to get rationale, but rationale can mean a lot of different things here. And so I'm just curious here whether -- if you were to put yourself in our shoes, right, or investors' shoes for a second, is this the right way we should be looking at this, that it is going to be more or less an interval to the external, but to the internally, you guys will have a lot more data? Or are you guys thinking about this as there will be things that you can share that will make this an interpretable catalyst? And then I have a follow-up.

Thank you for your question, Salim. I would like to say that we believe that what will we communicate in July is going to be something important for investors in giving them further understanding of the potential for this unique therapy to be successful at the end of the development. And the reason we can say that is it allows to not only clarify sample size, as you said, but also the timing of the completion of the study, which then will have an impact on the timing of the different steps to further develop that product. The fact that this data will also be shared later on with the FDA and potential partners is also a way to create further value. But coming back to the rationale, the reason we have not been able so far to give a lot of specifics to what this rationale could be is because it ultimately depend on the data. But our intent is very clearly to give that rationale information of relevance for investors so they can form their own view about the likelihood of success of that program. This program, as you know, is very unique. I don't know many program in the biotech today industry that have that potential for value creation if you think about the potential of disrupting a very important disease area with unmet medical need. We have, however, to focus our mind on creating value. And to create value, we need to make sure that we do not damage the integrity of that study -- that Phase II study. But again, what we'll be communicating, we believe, will be an important information for investors to form their own view on the likelihood of success of that program.

Is it out of the cards here to assume that -- or is there a possibility here that when you put out the qualitative readout that you would benchmark it somehow to the Phase I data or the MedDay placebo movement? Or are you guys thinking that, that would break the integrity of the study at this point?

We -- our intent is to be able to be as clear as possible about why we're taking that particular decisions about the size and the timing of the completion of the study. So the more details we can give, the better I understand. But at the same time, we want to preserve the integrity of the study. So we believe that the color we'll give or the qualitative aspect of why are we making that decisions is going to be something important for investors because it is going to give an idea about how management thinks about the likelihood of success of that particular program before there is further confirmation about this interpretation of the data by the discussion with potential partners at a later stage. So again, we cannot today give you details about how much we will say about confirmation of the Phase I data or confirmation that the placebo arm is aligned with what has been seen with previous studies like the MedDay's studies you are referring to, but we'll certainly try to give as much detail as possible while preserving the integrity of the study.

Our next question comes from Tessa Romero with JPMorgan.

So for our first one, can you provide a bit more color on why you don't think there will be an impact to the approval of tab-cel in Europe given the shift to a standard assessment? And then our second question is just one on ATA188. What activities are expected to occur at Atara between the interim and the disclosure of the EMBOLD study?

Thank you, Tessa. Jakob, do you want to take the first question, and AJ will take the second one.

Certainly. So Tessa, thanks for the question. So as Pascal described, EMA has transitioned the tab-cel MAA to standard review. And this is -- this allows the agency to additional time to review the company's answers to the EMA questions. But as Pascal also mentioned, we feel confident in our responses that we're going to be able to address those questions. So the result of the extension is just an additional 30 days for that review. But I think the most important thing here is that we're still on track for that EC approval in Q4 of this year, which is really the target that we're seeking. So in essence, yes, standard review, very addressable. And we're still on track for our ultimate goal.

Does it answer your question, Tessa?

Yes, that answers it. And then the one on ATA188?

AJ?

Sure. And thanks for the question. Maybe I can ask for a clarification. You're asking what activity between IA and disclosure of EMBOLD. What -- are you thinking disclosure of the final 1-year results of EMBOLD? Is that what the --

No. Just the kind of the differentiation between kind of an interim in June and a disclosure to us in July. Is it just like the -- yes.

Got it. No, thank you for clarifying. The -- when we do the interim analysis, I think we've mentioned it before that we're really going to look at everything. So this isn't going to just be, let's take a look at the EDSS. We'll be looking at EDSS. We'll be looking at the full safety profile, every piece of information we have on the secondary parameters, biomarkers, MRIs, et cetera. So really, we want to have a chance to take a look at those data, analyze the data, make good, clean decisions based off of it and then communicate that to you all in July. So it's really giving us that time to assess all of that information in totality and then actually provide a crips response to you back in July.

Ultimately, it's just a few weeks we're talking about.

Yes.

Our next question comes from John Newman with Canaccord.

So the question is, if you see clear separation between ATA188 and placebo at the interim, could you disclose these rates to us in the third quarter? And wouldn't that be meaningful to investors? Second question I have is, do you also expect to report results at 12 months on the patients involved in the interim? Or would you wait until the study was potentially -- the final size of the study was established and then report perhaps 12-month data on all those patients?

So thank you, John. I'll start, and AJ, you might want to chime in if needed. So just to be clear, reporting the percentage of response in terms of confirmed EDSS improvement in active versus placebo is, we believe, a level of details on the data that could jeopardize the study value or the integrity of the study in a sense that this being made public would influence the behavior of patients and physicians in a study that will still be enrolling and still be evaluating patients over time. So that's why we believe at this stage that it's not possible to disclose the percentage of confirmed EDSS improvement in active versus placebo. Now to your second question -- and that's something, by the way, we will do at the time of the July communication will be to clarify when the study will end, the last patients' visit in some ways, and then when do we plan to have results available for disclosure. And clearly, that's going to be a year after the last patient enrolled that we can have the last visit and then, as usual, a couple of months before 1 can have the data cleanup and QC. So you can communicate on this data, whatever the form of that communication will be. So we're not going to be able to present 12-month data on the IA patients in the middle of that. Is that clear, that the communication of EMBOLD will be at the end of the study, which mean 1 year after -- 1 year plus a few months after the last patient has been enrolled?

Yes. That's clear.

That we're planning to -- yes, sorry, that we're planning to enroll patient 80 soon after the IA. So that's also something important to keep in mind for the end of the study in the current target enrollment goal and the time of communication of the final results.

Our next question comes from Marc Frahm with Cowen and Company.

Congrats on the progress on the EMA review in terms of getting to the confirmation of comparability. My question is on that, the comparability established on the full -- everything you made commercially and kind of filed with initially and plan to file within the U.S.? Or maybe have you used the kind of day 80, day 120 process to I think go down one of those paths that you're proposing to the FDA, just on kind of within the review for the EMA?

I understand well your question. I mean we -- the day 120 -- maybe I'll come back to the EMA process. Once you file the MAA, you cannot file additional data then. So the day 120 list of questions and critical assessment report is really based on the initial data you filed for approval. So based on this initial data, which we're, of course, presenting all the comparability studies we have done for the clinical process version versus the commercial process versions, that's on the basis of this data that the reporter, co-reporter and basically the CHMP at EMA, the committee, has confirmed that the data support comparability, okay? So that's the same data set that we had also at that time. You remember that we filed in November. We had also sent for the FDA Type B meeting that we had in February. So the same type of data set from that point of view. What -- we've not given any additional data to the EMA at this stage, but they've evaluated the data that we had put together. And you remember, we always said we believe that these data confirm comparability. That is very clear, very good data, very strong data. And that's what has been confirmed by the review of the EMA or this CMC part of the file.

I guess to follow-up, Pascal, I think one of the -- my understanding, at least, one of the proposals you plan to put in front of the FDA, right, is to just simply restrict the range of commercial lots that you're actually going to use commercially to the ones that meet the release criteria of product that was used in the clinical trial. Have you gone down that path with the EMA? Or are you still intending to commercialize in Europe with the full range of commercial lots that were made?

Yes. With the full range of commercial lots because that's on that basis that we -- since we've established comparability, that will be the basis of the specification.

Okay. Great. And then maybe for -- coming out of the interim, you've laid down some general terms, some of the next steps, not just on the Phase II in terms of the resizing, but that this is going to impact maybe how you think about Phase III, potentially going into some other indications as well. Can you just kind of run through some of the options within there and what you might be willing to pursue yourself as Atara versus potentially needing to bring in that partner and kind of have that in place before you could go down those paths?

Yes. Maybe I start and, AJ, if you want to chime in. There are 2 aspects. One is, why are we considering that IA as a key milestone to then move into preparing the Phase III and potentially starting other the Phase II? It's because that this will allow us to have additional data compared with the Phase I, especially here versus placebo in additional number of patients. And that will allow us to have a safety database. That will allow us to go into new indications. And then, of course, to have enough confirmation, we hope, of the type of difference between active and placebo, that will allow us to optimize the design of the Phase III studies. As you may remember, we've discussed already design of Phase III studies with the FDA as part of the Fast Track designation process. And there was some alignment on potentially doing 2 Phase III study: one in nonactive SPMS, one in nonactive PPMS. So having the data from the IA will allow us to fine-tune that design and to further discuss with the FDA and to start preparing the Phase III. So I'll stop there before talking about when exactly -- and [linked] with partnering. But does that answer your question on that part about what type of steps we will take?

Yes. That's very helpful.

AJ, anything to add to that? So on the partnering aspect, by definition, moving into Phase III, moving into other Phase II is something that requires financial and operational capability. So there is some step that we can start immediately after the IA, which is certainly preparation. And we have already -- as you can imagine, we're already planning for that. I mean it's not suddenly we'll have to do all the work to prepare. We're already planning, whether it's on the manufacturing side, on the inventory, on this new manufacturing process version that we want to use that is being made, making the product stirred-tank bioreactors in terms of looking at the different sites and so on. So there is a lot of things that we can start to do before even the partnering is negotiated and executed. And then the idea of the partnering will be able to accelerate and expand activities so we can accelerate and expand value creation for the product.

Okay. That's very helpful. And then maybe the last piece is just on the potential additional Phase II. So do you want that kind of Phase III comparability and production up and running before you would do any more Phase IIs? Or we'll use the existing process for that and therefore --

No, we can use – sorry, we have inventory of the existing -- sorry, we have inventory of the existing process, so we can start studies with the existing process because they are Phase II. They are not pivotal Phase III studies. So it's really for the pivotal that our aim is to have a product that is then the same as the one to be commercialized, which will then allow to avoid any particular debate on comparability.

Our next question comes from Ben Burnett with Stifel.

This is Neil Carnahan on for Ben. On ATA2271, you conveyed that you guys believe the cause of the patient death was not due to 2271. Could you just help us understand your viewpoint here?

Jakob?

Yes. I'd be happy to do that. So Neil, thanks for the question. So as we detailed here in February of this year, Memorial Sloan Kettering notified the FDA of this serious adverse event and this very unfortunate patient demise. And they put the study voluntarily on pause, which the FDA agreed with. And then Memorial Sloan Kettering and the investigators there have been proceeding forward with the autopsy and a number of additional studies that are, in fact, still ongoing. So there is additional data coming in. So these additional analyses and so forth, we believe in review of information regarding this case and additional information that it's unlikely that this is an event that's caused by 2271, by the autologous CAR T against mesothelin. And then additional analyses are currently under review at Sloan Kettering, and we will be able to comment further on those once the data have been shared with the FDA.

Our next question comes from Jonathan Miller with Evercore ISI.

I guess maybe I'll sneak in one on ATA188. Suppose the IA hits that improvement bar that you were talking about from the MS Day that you did. In that scenario, would you need to increase the size to get to the powering you're looking for? I'm just trying to get a sense for what the stats bounds are for the potential upsize trials that you're looking at. And then maybe secondly, not on ATA188. It feels like the tab-cel regulatory process is still treading water a little bit in the U.S. And I feel like we haven't gotten a ton of clarity since we started talking about this last month -- or a little while ago before that, I guess. At this point, what needs to change to move forward there? And if the agency sort of puts their foot down on requiring an additional study, what would that look like? What's your willingness to run an additional study? Under what circumstances would that make sense for you guys?

Thank you, Jon. AJ, do you want to take the first one and then Jakob?

Sure. Thanks for the question. And we haven't commented specifically on the statistical bounds we've used for the study. We have commented on the types of information that we've used to inform our approach. And just as a reminder on the types of information, there's -- we've talked historically about the MedDay study when you look for what should we expect for placebo from nonactive disease. And the MedDay study that specifically looked at almost exactly the same population we're talking about, one study had 0% and one study had 6% EDSS improvement at that 12-month time point in those nonactive patients. Now I think the second piece of information that informs that is recent publications that we put out at ACTRIMS and AAN, where we showed that in a full PPMS population. So we didn't have a breakdown of nonactive and active in that particular data set from the multiple sclerosis outcomes assessment consortium. But for PPMS, it was 5.6% and for nonactive SPMS, it was 4%. So again, we've got a pretty good sense on what we should expect from placebo in these populations. And then certainly, from what we should expect from ATA188, we've talked about the 33% improvement, for EDSS improvement at 12 months, we saw in the high-dose cohorts for the ATA188 Phase I study. So again, that's the information that we've generally used to inform that statistical design, but we have not and probably would not comment at the time of the IA on the specific numbers there.

But what also I could add is that if we are -- based on this information we've used, if we are aligned with our statistical assumptions, we should not increase the number of patient, which should maintain AT. And therefore, we'll have the patient AT and all -- soon after the IA. Jakob, the second question?

Yes. Absolutely. So Jonathan, just to speak a little bit more about the FDA and tab-cel situation as you were asking about, as you know, we did have the Type B CMC meeting with the FDA here in late February. And at that point, the discussion was about the comparability between the manufacturing versions of tab-cel between the pivotal study and the intended commercial material. We were not able, at that time, based on the discussion to align on comparability. Subsequently, we have received the final minutes from the FDA, and that confirmed that the agency recommended that we conduct a new study with the commercial product. So we do not feel that, that is required. And following the Type B CMC meeting, we have remained in active dialogue with the FDA. And as you've already heard on the call today, we have made several proposals to enable a potential filing of the BLA that does not require a new clinical study. And some of the specifics of what we have proposed include that we would only use commercial lots that meet the range of specifications for clinical-use process version lots. So that's the first aspect. Secondly, we would use data generated by already having commercial product in the clinic. So we feel we can appease the agency by providing clinical data from patients treated with commercial material. And we did describe it the last call that we have already filed that IND amendment, and patients are actively being treated. And the third component of our proposal is that we are willing to proceed with post-marketing agreements as well with the FDA for appropriate monitoring of these patients. So long story short, we believe that these proposals really reflect tab-cel's clinical and commercial product data that we've generated to date; also, the important BTD status of this product to address an urgent medical need with these patients who have really a lethal disease with no therapeutic options, and this is an ultra-rare disease state where, again, the conduct of an additional clinical trial we do not believe would be appropriate. So importantly, the FDA is reviewing proposals currently, and we expect to be able to provide an update on the potential BLA pathways forward in the next few months.

And if you think about it, Jon, I mean, the Type B meeting was late February. We are early May. So what, 2 months and a few weeks. That's it. So we've been active, and we've had -- we've been -- we had discussion. We have support also. It's not like there have been a very long time between that particular Type B and now.

Okay. Fair enough. I guess, maybe beyond this initial indication, if this impasse doesn't get resolved or the FDA really puts their foot down on wanting another trial and you don't want to do that, does that have impact on other indications for tab-cel? Does the potential for an indication-agnostic approval really depend on the product already being approved in PTLD?

The study that is on the multi-cohort study, and Jakob, you might want to chime in, is designed as a label expansion study. However, of course, the data will be available -- start to be available next year and then depending on the cohort and the speed of enrollment of these cohorts following that, but there will be data at some stage available. Now again, our aim today with the first indication in second-line PTLD is to clarify the BLA pathway without doing another Phase III study for that particular indication and then to be able to move forward with our proposal. So in that type of scenario, we're still having the multi-cohort study data for potential label expansion coming after a BLA filing and hopefully approval.

And maybe I'll make one other comment. The multi-cohort study which is currently enrolling, and we're also using commercial material obviously in the clinic for the -- for both studies and also for expanded access and compassionate use and so forth, that study is ongoing, generating data. And obviously, with our progress in Europe, we intend for this to be label expanding in Europe as well. And so I do think that there's a lot of data being generated on tab-cel, and we believe that there are other mechanisms whereby we can solve this FDA impasse.

Our next question comes from Salveen Richter with Goldman Sachs.

This is Matt on for Salveen. I just wanted to know, what are you hoping to see in the multi-cohort data read in 2023? And what would give you confidence that tab-cel would demonstrate benefit in these additional populations? And then separately, what will be included in the Phase I update for 2271? And does the enrollment pause affect will be presented?

Thank you for your question, Matt. Just to be clear on the multi-cohort, and Jakob will develop that, we have already presented in different congresses clinical data on efficacy and safety in each and every of these cohorts over the last few years. So that is ultimately what makes us very confident that we should be able to have data from that particular study that replicates what we've seen in the past. Jakob, do you want to elaborate on that?

Yes. I think that's right. So in essence, we feel that we have proof of concept in all 6 of these cohorts that are included in the multi-cohort, meaning that these are really the same therapeutic hypothesis as the PTLD setting, where you've got an immunosuppressed state in an EBV-positive individual, which then drives a lymphoproliferative disorder where tab-cel is quite effective. So for example, we have presented data on the AID-LPD indication and the PID-LPD indications, which are 2 of the multi-cohorts. And we've seen response rates on the order of 33% to 38% there in historical, Sloan Kettering and Atara studies as well. But as Pascal mentioned, we really have data in all 6 of these indications, and the product works. And now we're obviously doing this pivotal study there to generate the registration intent data that will allow us to file on these other indications. And as referenced, these could each be filed individually or there may be an opportunity for a tumor-agnostic filing as well.

And maybe the question in 2271?

Yes. Absolutely. So I think it's a good question about the 2271 mesothelin autologous program. So working with our partners at Memorial Sloan Kettering who are conducting this study, we do have this intent to put the data into a medical meeting here in the second half of this year. So certainly not unlike the ESMO IO presentation last year, where we presented safety data, some early efficacy data and biomarker data and PK data as well. I think we would seek to present similar types of data. Now there's obviously been this voluntary hold, which has delayed the enrollment of patients on study. But we certainly, depending on the medical congress that we're seeking and the re-initiation of enrollment, which we believe should occur, we'll be able to present data. We previously described that this patient who had the SAE event, that was the first patient on cohort 3 to be dosed. So certainly, as you can tell, we're in Cohort 3 now with study. And then pending re-initiation of the study and then enrollment, we'll be able to provide updated data in that case. And I will say, just to maybe reference why we think our CAR T platform could be quite good is that the PK data that we presented at ESMO IO showed persistence of these cells with the 1XX costimulatory domain out past 10 weeks at that early look at the data, which we think is quite compelling compared to other CAR T programs in solid tumors.

Our next question comes from Yigal Nochomovitz with Citigroup.

Can you hear me?

Yes, Yigal.

Okay. My question is, there still seems to be a little confused -- a little bit of confusion around what's going to happen at the IA. So it would be very helpful if you could just clearly delineate for everyone what the possible scenarios are for what could happen at the interim and perhaps rank order those scenarios from most to least likely.

Thank you, Yigal, for your question. So maybe I'll start and, AJ, if you want to chime in. The scenario that we are planning right now, kind of base-case scenario, is that the data we see at the IA are aligned with our statistical assumption in terms of the trend towards the target conditional power. And therefore, we enrolled patient 80, and then we stop enrolling patients or maybe a few patient that are in the process, additional patients. But we basically then follow and evaluate these patients for additional time and period to go to the end of the study a year later. So that's the base-case scenario because that's our plan. Now there is a scenario where we can increase the likelihood of statistical significance for that study in increasing the sample size. And in that case, we will need to decide by how many we need to increase in sample size. And we'll communicate that particular increase when do we expect to end the enrollment, and therefore, when do we expect to have the final results of the study and the rationale for that increase. So that's the other scenario we've been mentioning so far. But again, for us, it's not a base-case scenario. Best-case scenario is still that we just go and move forward with what we had planned because we hope that we will see results in line what we've seen so far. Now that's the most likely scenarios if you're thinking about rank order. Now there is also always the possibility that we have a futility analysis that shows futility of that study there. We don't believe that it's very likely, and AJ might want to detail that, but it's part of any type of IA. So that's a kind of low likelihood type of scenario. And then, of course, there's also a scenario that we've been discussing in the past, whether increasing significantly the number of patient could lead to possibly to use that particular study as a kind of pivotal study to file for accelerated approval. We believe that, that scenario is extremely unlikely as well. It's a bit like the futility one for various reasons we can detail. But just wanted to set the scene. And if you want, AJ, you can comment further, but at least that's the scene as we see it. Base-case scenario, 80 is fine. We move forward. We enrol the last patient, follow that patient for 1 year, then we have the data. Possibility to slightly increase the sample size to improve the likelihood of statistical significance at the end of that Phase II study, and we'll communicate in that case why. That's the 2 most likely scenario; and then 2 very unlikely scenario, fertility or a situation where we'll have the ability to move towards a conditional approval. Does it make sense, Yigal?

Yes. No, no. That was very, very helpful. Okay. And then just one more. Regarding the EMA questions that required EMA more time to review your answers. Was EMA also asking about comparability of clinical and commercial batches like FDA? Or did they have different types of questions?

No. I think they are typical type of submission question, which is a lot of detailed question and a lot of aspects of the data there and then. And we believe that we have all the answers, and we're putting together all the answers to this question. On the particular aspect of comparability, they put in the words of the EMA in their Day 120 Critical Assessment Report, which is still a preliminary assessment report, that they believe that the data support comparability between clinical and commercial. So this is not a debate with the EMA at that stage.

Our next question is from Tony Butler with ROTH Capital.

Pascal, simple question, I think. Based upon -- let's just assume a base-case scenario. Well, I guess you could argue even one where you could increase the size. According to clinicaltrials.gov, there are 31 sites that are or have been enrolling patients for ATA188. So the question is, do you communicate anything to those sites either at the IA or at the time of patient 80 such that they may, in fact, need to, I'm making this up, enroll an additional patient just if you were to make it even for all 31 because the size needs to go up by 31 patients or some other function? What's communicated to the clinical sites, if anything?

Thank you for your question. AJ, do you want to take that one?

Sure. Thanks for the question. Yes, I think the main thing that you'd want to communicate to the sites at that point is they're not going to get any detail on the outcomes of the IA, but they would get a very specific detail on saying, okay, here's now -- if we're going to increase sample size, here's now the total target sample size. And that's important, of course, because they're doing a lot of work to try to bring these patients in. And it takes time because they've got a prescreen, then screen and then go through all these procedures. So there's always that lag time, right? There's a lead time that you want to give them. So we want to be as open in communication as possible about any numbers increase, but that would be the limit of additional communications then.

That concludes our question-and-answer session for today. Thank you for joining the Atara Biotherapeutics’ First Quarter 2022 Financial Results Conference Call. You may now disconnect your lines, and have a great day