Atara Biotherapeutics, Inc. Q1 FY2022 Earnings Call

Good afternoon, everyone. Thank you for standing by, and welcome to the Atara Biotherapeutics’ First Quarter 2022 Financial Results Conference Call. 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 of 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 and 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.

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 two landmark publications 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 of 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. 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 preparations, discussing further development steps with the 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 discussions 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 the 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 the 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 transitioned tab-cel to a standard assessment review timeline. 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 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 leverages tab-cel's status as a BTD product, addressing an ultra-rare and urgent medical need as patients in second-line PTLD have 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 specifications 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 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 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 our Atara planned operating expenses over the multi-year publication 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’s planned operations into the fourth quarter of 2023. I will now turn the call over to Jakob to give you more details on ATA188 development and our CAR T programs.

Thank you, Pascal. With regard to ATA188, as Pascal mentioned, momentum and awareness continue to build following the two landmark studies in Nature and Science identifying EBV as the leading cause and trigger of multiple sclerosis. ATA188 awareness has increased in physician surveys conducted by Atara and by external parties as well. Of note, a longitudinal survey of a cohort of high-prescribing neurologists was conducted six 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 six 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 six 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 next steps, 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 serious 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 to differentiate it from existing products through three 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 six 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.

Our first question comes from Salim Syed with Mizuho.

I have a couple of questions about ATA188. Pascal, many around this area seem to believe that the readout may not be interpretable. We anticipate a sample size adjustment and some rationale, but that can vary significantly. I’m curious, if you were in our position, or if you were an investor, how should we interpret this? Will it be more of an external interval, while you will have more data internally? Or do you believe there will be elements you can share that would make this an interpretable catalyst? I have a follow-up as well.

Thank you for your question, Salim. We believe that what we communicate in July will be significant for investors, helping them gain a better understanding of the potential success of this unique therapy at the conclusion of its development. This communication will clarify sample size and the timing of the study's completion, which will also affect the timeline for further developing the product. We will share this data with the FDA and potential partners, which is another way to enhance value. The reason we haven't provided many specifics about our rationale thus far is that it fundamentally depends on the data. However, our goal is to share relevant rationale information for investors, allowing them to assess the likelihood of success for the program. This program is quite unique, and not many in the biotech industry today present a comparable opportunity for value creation by addressing a significant disease area with unmet medical needs. We must focus on creating value while ensuring the integrity of the Phase II study remains intact. Ultimately, we believe that what we communicate will be essential for investors as they evaluate the likelihood of success for the program.

Is it reasonable to assume that when you provide the qualitative readout, you might compare it to the Phase I data or the MedDay placebo results? Or do you believe that would compromise the integrity of the study at this stage?

Our intent is to be able to be as clear as possible about why we're taking that particular decision 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 context we will give or the qualitative aspect of why we are making those 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 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 allows the agency 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, thanks for the question. Could you clarify if you're asking about the activity between IA and the disclosure of EMBOLD? Are you referring to the disclosure of the final one-year results of EMBOLD?

No. It's about the difference between the interim in June and the disclosure to us in July. Is it just like that?

Got it. No, thank you for clarifying. 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, etc. So really, we want to have a chance to take a look at that 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 crisp 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 observe a clear difference between ATA188 and placebo at the interim, could you share those rates with us in the third quarter? Wouldn't that be significant for investors? My second question is, do you also plan to report results at 12 months for the patients involved in the interim, or would you wait until the final size of the study is determined and then report 12-month data for all those patients?

Thank you, John. I'll begin, and AJ, feel free to add your thoughts if necessary. To clarify, we cannot disclose the percentage of confirmed EDSS improvement in active versus placebo because doing so could compromise the study's value and integrity. Making this information public might influence the behavior of patients and physicians while we are still enrolling and evaluating participants. Regarding your second question, we will clarify the study's end date and the timeline for when results will be available during our July communication. This will occur one year after the last patient is enrolled, followed by a few months for data cleanup and quality control. Therefore, we will not be able to present 12-month data on the interim analysis patients during this period. Just to reiterate, the communication regarding EMBOLD will take place at the study's conclusion, which will be one year plus a few months after the last patient has been enrolled.

Yes. That's clear.

We are planning to enroll patient 80 soon after the interim analysis. This is also an important factor to consider regarding the timeline for the study's final enrollment goal and the communication of the final results.

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

Congratulations on the progress with the EMA review regarding the confirmation of comparability. My question is whether the comparability established is based on everything you initially filed commercially and what you plan to file in the U.S. Or have you considered using the Day 80 or Day 120 process to pursue one of the paths you're proposing to the FDA during the EMA review?

I understand your question. The Day 120 process is important to mention. Once the MAA is filed, no additional data can be submitted. The Day 120 list of questions and the critical assessment report are based on the initial data submitted for approval. Based on this data, we have presented all the comparability studies we conducted between the clinical process version and the commercial process versions. The data that the reporter, co-reporter, and the CHMP at EMA reviewed confirmed that it supports comparability. This is the same dataset we provided previously. As you may recall, we submitted in November and shared this data during the FDA Type B meeting in February. We have not provided any new data to the EMA at this point, but they have assessed the information we compiled. We maintain that this data confirms comparability, which is backed by a strong assessment from the EMA during their review of the CMC section of the file.

I would like to follow-up, Pascal. My understanding is that one of the proposals you intend to present to the FDA is to limit the range of commercial lots used to only those that meet the release criteria of the product utilized in the clinical trial. Have you pursued a similar approach with the EMA, or do you still plan to commercialize in Europe using the entire range of commercial lots that were produced?

Yes. We plan to use the full range of commercial lots because we have established their comparability, which will be the foundation for the specification.

Okay, great. Coming out of the interim, you've outlined some general terms and next steps regarding the resizing of Phase II, and this may affect your approach to Phase III, including potentially exploring other indications. Can you go through some of the options available and indicate what Atara might choose to pursue independently versus what would require a partner before moving forward?

Yes, I’ll start, and AJ can add if needed. There are two main points to consider. First, we view the interim analysis as a crucial milestone for advancing to the preparation of Phase III and possibly starting other Phase II studies. This analysis will provide us with additional data compared to Phase I, particularly against placebo in a larger patient group. It will help us establish a safety database and explore new indications. Additionally, we expect to gain sufficient confirmation of the differences between active treatment and placebo, which will help us refine the design of our Phase III studies. As you may recall, we've already discussed the Phase III study design with the FDA during the Fast Track designation process, and there seemed to be agreement on potentially conducting two Phase III studies: one for non-active SPMS and another for non-active PPMS. The data from the interim analysis will enable us to fine-tune that design, have further discussions with the FDA, and begin preparations for Phase III. I will stop there before discussing the timing and partnership considerations. Does that clarify your question regarding the steps we plan to take?

Yes. That's very helpful.

AJ, do you have anything to add? Regarding the partnering aspect, entering Phase III and other Phase II trials requires financial and operational capability. There are steps we can begin immediately after the IA, particularly in terms of preparation, which we are already planning for. We won't need to start the work from scratch; we are actively planning for various aspects, including manufacturing, inventory, and the new manufacturing process involving stirred-tank bioreactors while evaluating different sites. There is a lot we can do even before finalizing the partnership. The aim of the partnership will be to accelerate and expand our activities, enhancing value creation for the product.

That's very helpful. Regarding the potential additional Phase II, do you want to have the Phase III comparability and production established before proceeding with more Phase IIs? Or will you use the existing process for that?

No, we have inventory of the existing process, so we can start studies with it because they are Phase II and not pivotal Phase III studies. Our goal is to have a product that is the same as the one intended for commercialization, which will help us avoid any 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 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. 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.

Our next question comes from Jonathan Miller with Evercore ISI.

I would like to ask about ATA188. If the IA meets the improvement criteria discussed during the MS Day, would you need to expand the size of the trial to achieve the desired results? I'm trying to understand the possible limits for the trial expansions you're considering. Additionally, regarding tab-cel, it seems like the regulatory process in the U.S. is still stagnant, and we haven't received much clarity since our discussions last month. What changes are necessary to move forward? If the agency insists on requiring an additional study, what would that entail? Are you open to conducting another study, and under what conditions would that be feasible for your team?

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

Sure. Thanks for the question. We haven't discussed the specific statistical bounds we've used for the study. However, we have mentioned the types of information that informed our approach. As a reminder, we've historically referenced the MedDay study when considering expected placebo outcomes in nonactive disease. In that study, which examined a very similar population, one trial showed 0% improvement, while another showed 6% EDSS improvement at the 12-month mark among nonactive patients. Additionally, we have shared findings from recent publications at ACTRIMS and AAN that indicate a full PPMS population, showing 5.6% improvement for PPMS and 4% for nonactive SPMS. This gives us a solid understanding of what to anticipate from placebo in these groups. Regarding ATA188, we noted a 33% improvement in EDSS at 12 months for the high-dose cohorts in the ATA188 Phase I study. This information has shaped our statistical design, but we haven't and likely won't disclose specific numbers during the IA.

What I can add is that if our statistical assumptions hold true, we should not need to increase the number of patients, which will help maintain the patient AT. Therefore, we will have the patient AT shortly after the interim analysis. Jakob, what’s your 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 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. 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 in 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 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 discussions. 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 being conducted is a multi-cohort study designed for label expansion. The data will start to be available next year, depending on the cohort and the speed of enrollment. Our goal with the initial indication in second-line PTLD is to clarify the BLA pathway without needing another Phase III study for that indication, allowing us to move forward with our proposal. In this scenario, we will have the multi-cohort study data for potential label expansion after a BLA filing and, hopefully, approval.

I'll add one more point. The multi-cohort study is currently enrolling, and we are using commercial material in the clinic for both studies, as well as for expanded access and compassionate use. This study is ongoing and generating data. With our progress in Europe, we aim for this to lead to label expansion there as well. We believe a lot of data is being generated on tab-cel, and we think there are alternative ways to address the 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 what 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 six 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 two 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 six 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 the 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.

My question is regarding the ongoing confusion about what to expect at the IA. It would be very helpful if you could clearly outline the possible scenarios and rank them 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 enroll patient 80, and then we stop enrolling patients or maybe a few patients 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. The 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 with what we've seen so far. Now that's the most likely scenario 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 patients could lead to possibly using 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 enroll the last patient, follow that patient for one year, then we have the data. A 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 two most likely scenarios; and then two very unlikely scenarios, futility 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 questions, which is a lot of detailed question and a lot of aspects of the data there and then. 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, I have a straightforward question. Assuming a basic scenario, or even one where the size could be increased, clinicaltrials.gov indicates that there are 31 sites currently enrolling or that have enrolled patients for ATA188. My question is whether you communicate anything to these sites at the interim analysis or when patient number 80 is enrolled. Would they need to enroll an additional patient to ensure even participation across all 31 sites if the size requirement increases by 31 patients or some other factor? What information is shared with the clinical sites, if anything?

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

Sure, thanks for the question. The important message for the sites is that they won’t receive any specific details about the outcomes of the interim analysis, but they will be informed about the total target sample size if we decide to increase it. This is crucial because the sites are putting in significant effort to recruit these patients, which takes time due to the necessary prescreening, screening, and various procedures. There is always a delay involved, so we want to ensure clear communication about any increases in numbers. However, that would be the extent of communication regarding this matter.

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.