Earnings Call Transcript - ATRA Q4 2020

Operator, Operator

Good afternoon everyone. Thank you for being here and welcome to the Atara Biotherapeutics Fourth Quarter and Full Year 2020 Financial Results Conference Call. At this time, all participants are in a listen-only mode. Later, we will have a question-and-answer session and instructions will follow. As a reminder, this conference call is being recorded. I would now like to turn the call over to your speaker today, Eric Hyllengren, Vice President of Investor Relations and Finance at Atara Biotherapeutics. Please go ahead, sir.

Eric Hyllengren, VP of Investor Relations

Thank you, operator. Good afternoon everyone and welcome to Atara’s fourth quarter and full year 2020 results conference call. On today's call, members from the Atara executive team will provide an update on our 2020 financial results and operational progress and also review our upcoming key milestones and objectives. Earlier today, we issued a press release announcing our fourth quarter and full year 2020 financial results and operational progress. This press release and an updated investor presentation are available in the Investor & Media section at atarabio.com. Joining me on today's call are Dr. Pascal Touchon, President and Chief Executive Officer; Dr. Jakob Dupont, Executive Vice President and Global Head of Research and Development; Utpal Koppikar, Chief Financial Officer; Joe Newell, Chief Operations Officer; Dr. AJ Joshi, Chief Medical Officer; and Kristin Yarema, Chief Commercial Officer. We will begin with prepared comments from Pascal and Jakob, then open the call up for your questions. We would like to remind listeners that during the call, the company's management will be making forward-looking statements. Actual results could differ materially from those stated or implied by our forward-looking statements due to risks and uncertainties associated with the company's business. These forward-looking statements are qualified in their entirety by the cautionary statements contained in today's press release and the company's SEC filings. These statements are made as of today's date, and the company undertakes no obligation to update these statements. Now, I’d like to turn the call over to Pascal. Pascal?

Pascal Touchon, President and CEO

Thank you, Eric and thank you all for joining us this afternoon. In the fourth quarter of 2020, we advanced very significantly our three strategic priorities; Tab-cel, ATA188 in multiple sclerosis, and our next-generation allergenic CAR T programs. For Tab-cel, Atara is on track to complete a rolling BLA submission for EBV positive PTLD in Q3 2021. As a reminder, we have already completed the preclinical module 4 in alignment with FDA requirements. We are ready for initiating rolling BLA with this module once the FDA decides upon compatibility or not of the drug product manufactured by our academic partner for the historical non-pivotal studies and the one manufactured by Atara for the pivotal study. Recall that the FDA has already agreed that the non-pivotal studies will be supportive clinical data in the BLA submission in any case, and that this positive decision will just determine whether we provide the data as pooled or parallel analysis with a Phase 3 ALLELE data in a clinical module five. Meanwhile, we are in frequent and productive discussion with the FDA on the content of CMC module 3. In fact, we just had an informal teleconference with the FDA CMC reviewer late last week, and we are making progress with the agency on the final content of this module. Our plans remain unchanged, but we expect to initiate a rolling BLA and then complete the BLA submission with a clinical module in Q3 of each year once we add the final clinical data required by the FDA. And finally, in Q4, we expect to present data from the Phase 3 ALLELE study at an appropriate Congress. With regard to the Tab-cel Phase 2 multi-cohort study in patients with other individuals and count cells, the opening of the clinical study sites is accelerating and the sites are actively evaluating potential study participants. As a reminder, there are six study populations, which may support meaningful label expansion. The largest two are EBV+ AID-LPD and EBV+ PID-LPD for which there is a high unmet need and a similar mechanism of disease to PTLD. Most recently, new Tab-cel data in patients with life-threatening complications of EBV viremia were presented at ASH 2020, showing a 50% to 80% objective response rate and overall survival at one year of 100%, for a median follow-up of 14.6 months. Over the last 12 months, we have made significant progress on the manufacturing front in building Tab-cel inventory, successfully HLA matching 89% of patients eligible for screening in a Phase 3 ALLELE study. We are on track to reach our goal of over 95% of PTLD patients covered at the time of commercial launch. We have started to invest further in our U.S. commercial readiness activities in anticipation of Tab-cel approval and planned launch in the first half of 2022. We intend to undertake a very focused commercial approach consistent with rare disease models. By the way, yesterday was Rare Disease Day in the U.S., which we were proud to support as patients with rare cancers like PTLD need to know that they are not alone in their fight. Atara's activities are already underway for disease area education, identifying key providers accounts, and performing specific analyses to support the Tab-cel value story. We believe that the unique attributes of PTLD as a serious and deadly disease with no approved therapies, together with Tab-cel's potential unique benefits as a transformative therapy, support the targeted and highly efficient commercialization model. Regarding Tab-cel in the EU, which has time designation of Pediatric Investigation Plan or PIP was approved in December 2020. In the fourth quarter of this year, we plan to submit an EU marketing authorization application for Tab-cel in EBV+ PTLD. Recently, we announced we are seeking a partner for the commercialization of Tab-cel outside the U.S. and discussions with interested parties have started. Moving on to ATA188, our potentially transformational multiple sclerosis program for patients with progressive forms of MS. The rollout is progressing well in the Phase 2 randomized double-blind placebo-controlled study or RCT, following first patient enrollment in June of 2020. Atara will conduct an interim analysis for this study in the first half of 2022, including efficacy and safety in patients with progressive forms of MS. Following the interim analysis, we expect to complete enrollment of this Phase 2 study in the first half of 2022. Ahead of the interim analysis next year, we plan to present in the second half of 2021 long-term two-year clinical data from the Phase 1a open label extension or lead study, as well as translational data from the Phase 1a. Recently, we've seen increasing momentum from independent publications and review articles that reinforce the association between EBV and MS, as well as a possible rationale for EBV latent infection to be a triggering factor for disease progression. In parallel, we are seeing significant interest from patients, patient advocates, and physicians in our RCT and separately significant interest from a number of large companies regarding the potential for collaboration involving ATA188. Turning now to a differentiated next-generation CAR T portfolio. Atara CAR T programs are based on the EBV T cell platform and our ability to leverage new technologies such as novel co-stimulatory domains like 1XX, and novel armoring technology, like PD1 DNR to improve efficacy, persistence, and durability of response, hence addressing limitations of other allogeneic CAR T therapies. In December of last year, we announced a strategic collaboration with Bayer for the development of our CAR T program. While only a few months have passed since the collaboration began, the rollout has been very smooth due to the commitment of both parties to bring lifesaving cell therapy to patients and also both parties' prior expertise in targeting oncology indications. Our partnership with Bayer allows us to accelerate and expand the development of ATA3271, our allogeneic Mesothelin targeted CAR T, to parallel studies in multiple formats, potentially speeding its delivery to patients and creating shareholder value. Atara will perform IND enabling studies and process development for ATA3271. Bayer will submit the IND expected in Q2 or Q3 of 2022 and lead its subsequent clinical development and commercialization. For ATA3219, our allogeneic CAR T for patients with B cell malignancies, Atara recently presented exciting preclinical data that Jakob will detail shortly. We plan to submit an IND for ATA3219 in Q4 2021 or Q1 2022, in line with our strategic goal to develop the asset as best-in-class in B cell malignancies. Now moving on to our financials. With regard to cash position and runway, we ended the fourth quarter of 2020 with $500.7 million in cash, cash equivalents, and short-term investments. This cash balance includes the net proceeds from the upfront cash payment from the Bayer collaboration, proceeds from the December 2020 financing, and proceeds from stock sold through our ATM facility. With this cash balance and projected revenue from U.S. Tab-cel sales, we believe we are sufficiently funded into 2023, inclusive of expenses for the BLA filing and U.S. commercial launch of Tab-cel. Reflecting upon Atara in 2020, we acknowledge it was a highly unusual and challenging year for all due to the COVID-19 pandemic. I would like to express gratitude to our extraordinary Atara staff whose tireless efforts enabled the company to deliver on our milestones. Over the past year, we conducted the Tab-cel interim analysis, made significant progress on the Tab-cel regulatory front, initiated the ATA188 RCT, initiated a CAR T clinical study, and signed a CAR T strategic collaboration with Bayer. Not only did we meet these extraordinary milestones while doing what we said we would, but the Atara team also stepped up to support one another during the global pandemic, an incredible achievement. Atara's progress in leveraging our unique allogeneic EBV T cell platform to deliver transformative therapy to patients during a challenging year like 2020 is only possible because of the perseverance of Atara staff in collaboration with patients, caregivers, academic, and industry partners, as well as investors. I will now turn the call over to Jakob. Jakob?

Jakob Dupont, EVP and Global Head of R&D

Thank you, Pascal. Now, as Pascal mentioned earlier, we've made tremendous progress across all three of our strategic priorities in 2020 and are poised for continued success this year. For Tab-cel, we continue our plans to initiate the rolling BLA and are on track to complete the rolling BLA submission for EBV+ PTLD in Q3 of this year. We remain on track with and continue to have frequent and productive conversations with the agency on the most appropriate and expeditious pathway to approval for this lifesaving therapy. In addition, through our advanced and leading process science and manufacturing efforts, we have created reliable and reproducible allogeneic cell therapy products like Tab-cel and ATA188. Evidence of our advanced manufacturing was recently featured at last month's 2021 Transplantation and Cellular Therapy or TCT Meeting. At that meeting, we presented for the first time transcriptional data for Tab-cel demonstrating consistency of the products' activation profile, irrespective of donor and consistent enrichment of receptor targeting in EBV-driven diseases. The study evaluated the in-vitro characteristics of Tab-cel that help elucidate its proposed mechanism of action. These results demonstrated that upon stimulation, Tab-cel exhibits a consistent activation signature at a level of gene expression linked to cell receptor engagement and secretion of factors associated with effective T cell responses. We've made significant progress on manufacturing a consistent off-the-shelf drug product, which is critical in order to get Tab-cel to PTLD patients who have very limited options and can't wait. Continuing with our program ATA188 for Multiple Sclerosis. Recently, we provided an update on our discussions with the FDA regarding the ATA188 clinical data, the design of the randomized control trial, and potential registrational path for this potentially groundbreaking therapy for multiple sclerosis. Regarding the registrational path for ATA188, the FDA articulated a preference for an EDSS as the improvement endpoint and agreed that the patient population criteria that Atara used to define patients with non-active secondary progressive MS and non-active primary progressive MS are appropriate for registrational studies. Furthermore, the agency agreed that our Phase 2 RCT study duration should be at least 12 months after the initiation of treatment. Based on this feedback from the agency, we've amended the study protocol, changing the primary endpoint of the study to EDSS as disability improvement, assessed at 12 months, and increase the number of patients to 80 to accommodate for this change. Biological and functional endpoints will still be maintained. In our discussions, the FDA also agreed to an interim analysis in the ongoing Phase 2 RCT and that statistical power should be allocated to this interim analysis for the sake of rigor. The timing of the interim analysis and the Phase 2 RCT will be the first in the first half of 2022 and this will include efficacy and safety, and shortly thereafter, enrollment will be completed, also in the first half of 2022. We will have a number of options for the interim analysis data. Firstly, we can discuss with the FDA the potential to amend the study for registrational intent based on the FDA feedback. Secondly, with the data, we can discuss with potential partners opportunities for collaboration; and thirdly, we can make sample size adjustments to the trial since the interim analysis will occur before enrollment is completed. Furthermore, the body of evidence supporting the potential role of EBV in Multiple Sclerosis continues to grow as highlighted in the recently published New England Journal of Medicine review paper, by recent researchers from UCSF. This review paper adds new information regarding EBV and its involvement in Multiple Sclerosis. Now, we know that EBV is implicated in the pathogenesis of MS. Specifically, from other evidence, we know that 100% of MS patients are EBV positive. EBV infection appears to be necessary for the development of MS in genetically susceptible individuals. There's also a strong correlation between the presence of EBV antibodies in the blood and disease onset. EBV-infected B cells and plasma cells can also be detected in the brains of patients with Multiple Sclerosis and there have also been reports of elevated antibodies against EBV antigens such as EBNA1 being associated with more MRI disease findings in MS, like cortical atrophy. Now, with the New England Journal of Medicine publication, we find that there is another argument added to the EBV-MS hypothesis. Specifically, the publication reviews how EBV may be involved in molecular mimicry, in which protein sequences in EBV can induce a CD4 T cell immune response that can also target a protein in the brain. As such, EBV may trigger the pathological cascade of MS. As noted, the body of evidence for EBV as a causative agent for the development of Multiple Sclerosis is growing and we are enthusiastic about our ATA188 program that specifically targets EBV infected cells in Multiple Sclerosis with the hope of providing significant clinical benefit to these patients. Turning now to our CAR T programs. As Pascal mentioned, we recently started a strategic collaboration with Bayer for Mesothelin CAR T therapy specifically ATA2271 and ATA3271 for the treatment of solid tumors. Starting with ATA2271, or Autologous Mesothelin targeted CAR T, we've already started enrolling patients as performed by our collaborators at Memorial Sloan Kettering to an open label Phase 1 clinical study. ATA2271 incorporates both a novel 1XX co-stimulatory domain and a PD1 dominant negative receptor for intrinsic checkpoint inhibition. Initial Phase 1 safety and efficacy data for ATA2271 are targeted to be presented in Q4 of this year. We're excited about the potential for this innovative construct which is being used for the first time in this setting. We believe this approach could be a way to address the prior challenges other CAR T have had in successfully treating solid tumors. Now turning to ATA3271, the first preclinical results of ATA3271, our allogeneic EBV CAR T cell therapy targeting Mesothelin designed for the treatment of solid tumors, were presented at SITC recently. Findings from the in-vitro ATA3271 study show potent anti-tumor activity against Mesothelin expressing cell lines and potencies maintained in the presence of high tumor PDL1 expression. These data support the design of ATA3271 to maintain function in the presence of suppressive PDL1 expression commonly associated with solid tumor microenvironments, including mesothelioma, non-small cell lung cancer, and other solid tumors. In addition, results further support the combined functional design of ATA3271, 1XX co-stimulatory domain technology and maintaining a memory phenotype, while limiting cell exhaustion in the context of repeated tumor cell challenges, which could be particularly important for the success of CAR T therapy in solid tumors. Now, in-vivo, ATA3271 exhibits potent anti-tumor activity and significant survival benefit in mice implanted with mesothelioma cells that highly expressed both Mesothelin as well as PDL1. This in-vivo potency was demonstrated without evidence of toxicity such as allocytotoxicity. Both in-vitro and in-vivo results for ATA3271 suggested allogeneic Mesothelin CAR T engineered EBV T cells are a promising approach for the treatment of Mesothelin positive cancers. Now finally, with regard to ATA3219, our next generation off-the-shelf allogeneic CD19 CAR T utilizing again 1XX technology without the need for TCR editing for the treatment of B cell malignancies. We are on track to submit an IND in Q4 of this year or Q1 of next year. We presented promising preclinical data showing potent anti-tumor activity both in-vitro and in-vivo, with long-term functional persistence and no evidence of allocytotoxicity in-vivo at the December 2020 American Society of Hematology Annual Meeting. Preclinical results presented at ASH detailed findings from in-vivo and in-vitro evaluations of ATA3219. Specifically, the studies demonstrate potent anti-tumor activity of ATA3219 against CD19 expressing target cells and in-vivo against the disseminated tumor model of ALL. We believe these results are associated with long-term persistence and survival benefit. In addition, both in-vivo and in-vitro assessments of ATA3219 allocytotoxicity support a potentially favorable safety profile that would be required for an allogeneic off-the-shelf CAR T cell therapy. Together these findings support advancing ATA3219 to clinical evaluation. I would like to conclude by reiterating Pascal's comments of thanks to our Atara staff, collaborators, patients, and caregivers. We could not have accomplished this much in 2020 without your dedication to bring these lifesaving therapies to patients. I will now turn the call back to the operator to begin the Q&A portion of the call.

Eric Hyllengren, VP of Investor Relations

Hello operator, ready to begin the Q&A portion please. Well, operator, can you hear us? We're ready to begin the Q&A portion please?

Operator, Operator

Yes, thank you. We have our first question coming from the line of John Newman with Canaccord. Your line is open.

John Newman, Analyst

Hi, guys. Thanks for taking my question. Congrats on the progress in 2020, especially such a difficult year for everyone. I just have two quick questions. The first one regarding the Tab-cel rolling BLA submission; I'm just curious if the agency needs to come to a definitive conclusion as to whether they consider the prior Tab-cel material comparable to the current material? Or if perhaps you might be able to just submit both analyses at some point and let them choose? The second question on the Mesothelin CAR T program, just curious if we might happen to get an update from the study that Sloan Kettering had running, started a few years ago? I'm just not sure if they might give us an update earlier this year, or if we will wait for your product later this year? Thanks.

Pascal Touchon, President and CEO

Thank you, John, for your questions. Jakob, do you want to take the first one?

Jakob Dupont, EVP and Global Head of R&D

Sure. Thank you, Pascal, and John, thank you for your question. So, I'll begin by saying we've had productive and frequent discussions with the FDA, and that's obviously because of our breakthrough therapy designation status. The focus of the current discussions is to secure all the guidance that we need to complete our module three or the CMC module of the BLA. In parallel, with gaining the necessary guidance on completing module three, we also are expecting resolution to the procedural decision from the FDA whether we can submit the clinical data from the historical non-pivotal studies as pooled or parallel as you're alluding to, and that's obviously data with data from the 302 or LEO study. So, overall, we're very pleased with the progress that we've made with the FDA and we are on track, and this is really important, to complete the rolling BLA submission for Tab-cel in the third quarter of this year.

Pascal Touchon, President and CEO

Thank you. On the second question about the third generation academic study that was done with different Mesothelin CAR T, Jakob?

Jakob Dupont, EVP and Global Head of R&D

Absolutely. So, thanks for the question, John, on the academic Mesothelin program. So, importantly, for Atara, as you know, now in our partnership with Bayer, we have these two programs, 2271, which is the autologous program and then 3271 which is the allogeneic program. So those are the ones that Atara oversee in collaboration with our partners now at Bayer. Now, as you alluded to, there is an academic program that preceded the Atara partnership. And this had the Mesothelin binder in it and it was a more conventional or first-generation co-stimulatory domain there. Now, we are separate from that program; it's not part of the Atara partnership. So in that sense, we don't have insights into when the colleagues at Memorial Sloan Kettering are going to produce that data? But certainly, we look forward to any updates from them.

Pascal Touchon, President and CEO

Yes. And we know they're continuing to follow the patient. So one might expect some data at some stage, but this is not being supported or funded by Atara. Does it answer your question, John?

John Newman, Analyst

Yes. Great. Thank you very much.

Operator, Operator

We have our next question coming from the line of Salim Syed with Mizuho. Your line is open.

Salim Syed, Analyst

Thank you for the questions. I have a couple regarding ATA188. Pascal or Jakob, concerning the interim analysis planned for the first half of 2022, what would you consider to be the best-case, worst-case, and middle-case scenarios? We've touched on this before regarding the potential for a slight or significant increase. Is there a futility analysis involved? Could you provide some insight on how we should interpret the various scenarios emerging from the RCT, whether it be a small increase, a substantial one, or none at all? Additionally, I noticed in the slides that you're no longer presenting data from the first half of 2021 for the OLE, and I'm curious as to why that is. Thank you.

Pascal Touchon, President and CEO

Thank you, Salim for your question, AJ, do you want to answer the first question please?

AJ Joshi, Chief Medical Officer

Sure. Thank you for the question, Salim. Regarding the interim analysis, this will follow a traditional approach where we assess everything, including efficacy and safety. In these analyses, we assess all relevant parameters. The best way to interpret the results will be clearer as we finalize any adjustments to the design based on the interim analysis. We have a solid Phase 2 study design, and a slight increase in sample size may enhance robustness. A significant increase in sample size might arise from discussions with the FDA, leading to a more substantial registrational pathway. We aim to implement changes to the development plan, hopefully not too many, but it will depend on the interim results. We'll strive to offer clarity on this, although we won't disclose specific data from the interim analysis until the end of the primary observation period or the completion of the study.

Pascal Touchon, President and CEO

And I could add that the base case scenario for us is that the study is powered to be at the right level for a potential significance between placebo and absolute treatment there. So having to increase the sample size, to a certain extent, is something that will just increase the robustness of leads as a Phase 2 study. But as AJ said, the best case scenario will be really that we can further increase the sample size to make it one of the pivotal studies that we might want to see. And that will be done in discussion with the FDA, because we can discuss the detailed data with the FDA, which is something that will be important for the next step moving forward there. Now, on the second question, AJ, you like to comment on the new data coming for the OLE.

AJ Joshi, Chief Medical Officer

Sure. And to your question around the timing of the data. Now, as we've been going through this, you've seen that we've provided data, almost like three-month updates; at this point, it doesn't really make sense to keep dribbling that data out. What we really want to think about is now, what are the meaningful data releases that we're going to have. And what's nice about that second half is it allows us to have a full two-year readout on the open-label extension study. So that's why we're targeting the second half, is to give a meaningful two-year readout for all the patients.

Pascal Touchon, President and CEO

And we also hope to have some translational data available by that time from the Phase 1a study that we are conducting.

Salim Syed, Analyst

Great, super helpful. Thanks, AJ. Thanks, Pascal.

Operator, Operator

We have our next question coming from the line of Michael DiFiore with Evercore. Your line is open.

Michael DiFiore, Analyst

Hey, everyone. Thank you for taking my question and congratulations on the progress. I have two questions about ATA188. First, regarding the change in the primary endpoint from sustainability improvement to EDSS, did the FDA mandate this change, or was it preferred? Does this affect your confidence in the program, considering any potential benefits in the 25-foot walk that may have occurred? And I have a follow-up question.

Pascal Touchon, President and CEO

AJ, you want to take that one?

AJ Joshi, Chief Medical Officer

Sure. Thanks for the question. It's a good question. Really for us, the good news for us to really throughout the entire Phase 1a program is when you look at the basis of improvement that we saw in sustained disability improvement, the vast majority of it was driven by EDSS. So from our perspective, it actually doesn't really hurt us at all, in terms of the likelihood of success at the end of the study when we focus just on EDSS. Because, again, all of that improvement, the majority of that improvement was driven by EDSS. We did make a small sample size adjustment issue to the 80 patients. So you can see it's a very minimal adjustment to account for that change. But our confidence is high. Because whether it was in the main 12 months of study or to the open-label extension, we continue to see EDSS as a driver of improvement.

Michael DiFiore, Analyst

Great, that is helpful.

Pascal Touchon, President and CEO

And do you have a follow-up question?

Michael DiFiore, Analyst

Yes, I do. My second question is about the interim analysis for ATA188. It seems that after the interim analysis is conducted, but before the enrollment is complete, a discussion with the FDA will take place. What do you believe the FDA will be looking for in terms of the treatment effect on EDSS to support moving forward and expanding the trial enrollment to a registrational study?

Pascal Touchon, President and CEO

AJ?

AJ Joshi, Chief Medical Officer

I think there are a few key aspects we need to align on with the FDA regarding our target population. As you know, we are focusing on non-active Secondary Progressive MS and non-active Primary Progressive MS. It's essential to determine whether the FDA wants us to treat these as separate or combined populations. This is crucial because we're conducting the study, and we have it structured robustly enough to handle either scenario. The next steps are vital here. Over the next couple of months, we expect to reach an agreement with the FDA on their preferences. Once we conduct the interim analysis, it will enable us to apply for an expedited pathway, which requires a clearly defined target population. Identifying this specific population is a significant step towards applying for the express pathway, which is also important from a registration standpoint. So, we will focus on this aspect leading up to the interim analysis. To answer your question about what would make the interim analysis registrational, we need that alignment with the FDA. Additionally, it will depend on when the interim analysis is conducted and how we interpret the datasets, particularly concerning population dynamics and the early results we observe from the interim.

Pascal Touchon, President and CEO

Yes. And I will add that, as usual, we will also see like to see of course, a significant difference between placebo and active treatment. And then the question will also be about the safety database, how many patients would like to see to transform this oldest Phase 2 into the regulatory pivotal trial there? So, that's a different aspect we discuss with the FDA. And that's why we plan that i.e. before finalizing the enrollment, because when we say that, we'll finalize the enrollment in the first half of 2022, that's what Phase 2 of the study to then go to pivotal program. But of course, if the FDA aligns with us, and they say, on one hand, you have a significant difference versus placebo, and you have good safety on your patients, but they would like to see more patients there. And at the same time, there is the clarification on the population, then that allows us to expand that study before it's fully enrolled by definition, want to expand it before there. And that's why the timing is very important. And we have very well organized to really address that particular timing aspect of firstly, interim analysis, then the finding duration of the enrollment, depending on the discussion with the FDA.

Michael DiFiore, Analyst

Very helpful. Thank you.

Operator, Operator

We have our next question coming from the line of Anupam Rama with JPMorgan. Your line is open.

Anupam Rama, Analyst

Hi, guys. Thanks so much for taking the question. On the ATA188 Phase 1 presentation in the second half, you mentioned a couple of times on this call some translational data that will be presented at the conference; maybe you can give us a little color on what specific translational analyses we should be focused on? Thanks so much.

Pascal Touchon, President and CEO

Thank you Anupam for your question, AJ?

AJ Joshi, Chief Medical Officer

Yes. So thanks for the question, Anupam. I think we've got a variety of different translational elements that we've looked at in the Phase 1a study. We've mentioned previously that we're working on that assay to detect ATA188 in the serum and CSF and we've conquered kind of the main technological barriers; now we're just looking to validate that assay. That's one component that we might see. There are other things, as you know, in the study that we've had different elements of MRI results and some other biomarkers that we assessed in the Phase 1a study. So, some of those may also be possible to present in the second half. So, right now, we're just putting some of those data together and there will be some combination of those elements that we anticipate in the second half.

Anupam Rama, Analyst

Thanks so much.

Pascal Touchon, President and CEO

Thank you, Anupam.

Operator, Operator

We have our next question coming from the line of Salveen Richter with Goldman Sachs. Your line is open.

Unidentified Analyst, Analyst

Good afternoon and thank you for taking our question. This is Elizabeth on for Salveen. Just wondering if you could talk a little bit more about your commercial readiness plans ahead of the Tab-cel launch in the first half of 2022, what that could look like, and then what a sales force might look like there?

Pascal Touchon, President and CEO

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

Kristin Yarema, Chief Commercial Officer

Yes. Thanks for the question. So PTLD, as we know, is an ultra-rare disease. And so consistent with that, we're really looking at a commercialization approach that's very much in the model of a rare disease model. So that will include a very limited number of highly specialized commercial as well as medical field staff. And then we will have – we’ll be supplementing that with different sorts of communication, multi-channel, peer-to-peer congress and so forth.

Pascal Touchon, President and CEO

Thank you. And I think what I will add as well is that these patient population of PTLD; first-line therapy is very well identified. I mean, these patients have gone for transplants and they have unfortunately been diagnosed with PTLD. They've added their value setting including EBV positivity of PTLD. Then they get the first-line treatment, which could be, as you know, rituximab, or rituximab plus chemo, and then really, they’re well identified. So what's important from a commercialization point of view is that at that time the physicians will be aware of Tab-cel and be able to plan in advance in case the patient does not respond to first-line therapy, or is relapsing after response to first-line therapy, but can immediately access Tab-cel. So this ability to identify the patient early on in their pathway is extremely important in the way we're going to commercialize Tab-cel to make it a product that is sufficiently available in a way for the physician, so they know when to act for their patients in the best interest of their patient's care. Does it answer your question, Elizabeth?

Unidentified Analyst, Analyst

Yes. Thank you.

Operator, Operator

We have our next question coming from the line of Ernie Rodriguez with Cowen and Co. Your line is open.

Ernie Rodriguez, Analyst

Hi. Thank you for taking my call and my question. My question is about the commercialization of Tab-cel. You mentioned considering partnerships for commercialization outside the US. Could you provide more details on that? Specifically, are you focusing on certain indications in particular geographies, or what is your approach? Thank you.

Pascal Touchon, President and CEO

Well, thank you for your question. So in terms of partnering discussions ex-US, we have initiated a number of discussions with interested parties that are really focused, or first on Europe, because as you know, we have a very clear line of regulatory pathway in Europe, Jakob Dupont has mentioned our regular interactions with the reviewer there in Europe. So we know exactly what is needed there. And we know the timing for submissions now that is planned for Q4 2021. So that means these key regulatory pathways in order to have a discussion with interested parties, so they get ready to be able to launch Tab-cel in Europe in the second part of 2022. The type of partner we're looking for is a partner that has already an infrastructure for commercialization in Europe, around hematology, transplantation, and rare diseases in oncology in general, because that's where this partner could really leverage that infrastructure in creating further value with such transformative therapy that, as you know, is a therapy that is much easier to deliver and supply than for example, autologous CAR T because this is truly an off-the-shelf product. So the partner just adds to the commercialization and of course, medical infrastructure there to handle such a product to get access. But the delivery and supply could easily be managed by Atara product partners in this type of geography. And in fact, we already have experience of that, because we have opened clinical sites for pivotal study and for the 205 study in Europe, so we are already delivering in Europe Tab-cel as we speak to these clinical sites, when there is a patient included in a study. We've also conducted a NAAQS program in Europe which was to treat patients there. So that experience is really at Atara. And we will be looking for a partner that can prolong that experience into the wellness and commercialization of Tab-cel in Europe. Beyond Europe, it will be really depending on the type of partner we're talking to; because some of them might have an interest. We have already experienced in Australia, of course. We are also opening a site now in Canada. So there are a number of geographies where there is already the possibility to treat patients and it might be an interest for partners there as well. Does it answer your question?

Ernie Rodriguez, Analyst

Yes, very helpful. Thank you.

Operator, Operator

We have our last question coming from the line of Matt Phipps with William Blair. Your line is open.

Matt Phipps, Analyst

Hi. Good afternoon. Thanks for taking my question. Just wanted to clarify the discussion with the FDA around the final content for CMC module 3? Is that related to the procedural question on the non-pivotal data? Or is that a separate discussion?

Pascal Touchon, President and CEO

Thank you, Matt, for your question. Jakob?

Jakob Dupont, EVP and Global Head of R&D

Yes, absolutely. Thanks for the question, Matt. We’ve had several productive discussions with the FDA about module 3, and we want to secure responses regarding the guidance for the CMC content of the BLA. Along with that guidance, we’ll also receive direction on the presentation of the historical non-pivotal data. These topics are interconnected, but our main goal is to obtain all the necessary guidance to complete module 3 for the BLA.

Pascal Touchon, President and CEO

Yes. And I will add to that also that having this alignment with the FDA on the content of module 3 is something very important in advance of the submission to optimize the chance of success in the BLA submission, and the FDA agrees with us. That's why we are talking in advance and we have this breakthrough designation status that enables us to have very frequent and productive interaction with the FDA. In fact, if you think about it, we are the first company coming to the FDA with a BLA submission for allogeneic T-cell therapy. The FDA knows that in fact, we are the experts on the product and the goal of the ongoing discussion is make sure that we fully align before the submission. And it's not a gating factor, because we know that the gating aspect is more related to the maturity of the clinical data that allows us to be able to finalize the submission into FY 2021. But all this work, all the progress we are making now is really there to optimize the chance of success in a BLA submission, especially on the CMC aspect of the file. Does it answer your question?

Matt Phipps, Analyst

Yes, I think so. And then have you submitted any additional data to the FDA? Because maybe comparability assays or something like that, since you started having these discussions on the procedural question?

Pascal Touchon, President and CEO

Yes, when we’re discussing about Module 3, in fact, it's not only a discussion in principle; it's a discussion based on data. So we are submitting to them data for the typical Type B setting. We have already had in the last few months two Type B meetings on different topics with them on the CMC file where we submitted data and we discuss this data. And then how do they want to see the data being presented in the final submission. So it's not only a conceptual description; it's really a data-driven discussion, which I think is very important to make progress here.

AJ Joshi, Chief Medical Officer

Yes. I would like to add that for each of these interactions, we prepare formal briefing books that are submitted prior to the Type B meetings. There are also requests from the agency for additional information that we provide to our reviewers at the FDA. This engagement with the FDA is very rich, productive, and frequent on this topic. Even during what we refer to as informal calls, like the one we had last week, we sent them a comprehensive briefing book containing all relevant data analyses and details that we believe are important for discussion, even in an informal setting, which is distinct from the Type B meeting.

Matt Phipps, Analyst

Great. Thanks.

Operator, Operator

We have our next question coming from the line of Maury Raycroft with Jefferies. Your line is open.

Ken Chan, Analyst

Hi, this is Ken Chan on behalf of Maury Raycroft. Regarding ATA188, can the current Phase 2 serve as registration? What data does the FDA require for accepting a combined PPMS and SPMS arm compared to conducting separate trials for each arm? Thanks.

Pascal Touchon, President and CEO

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

AJ Joshi, Chief Medical Officer

Sure. We are generating one set of data based on EDSS as the disability improvement endpoint. The main point we are aligning on is which population we are considering. We refer to it as a single non-active progressive MS population, and experts in the field generally agree that progression in this area is similar across both settings. That's the basis of our approach. If the FDA chooses to evaluate the population separately, they will still assess the endpoints in the same manner. Therefore, we need to differentiate between ATA188 and placebo within whichever population they decide on. There is no difference in the approach; it's just about identifying the population.

Pascal Touchon, President and CEO

And that's why if I may add what we say, that this Phase 2 study, we're running right now the randomized control trial, in fact, adapted to either scenario from our point of view. And that's great, because that's the most worthy discussion with the FDA and then the interim analysis. And then to adapt to whatever alignment we have with the FDA there. Does it answer your question?

Ken Chan, Analyst

Yes, thanks.

Operator, Operator

We have our last question coming from the line of Yigal Nochomovitz with Citi. Your line is open.

Unidentified Analyst, Analyst

Hi, this is Carly on for Yigal. Thanks very much for taking our questions. For MS, can you just talk about how changing the primary endpoint to EDSS impacts the interim analysis if it does at all? And can you just remind us of what triggers the interim analysis, and whether increasing the enrollment means you'll need to enroll more patients to trigger the interim or does that trigger not change? Thank you.

Pascal Touchon, President and CEO

Thank you for your question. AJ?

AJ Joshi, Chief Medical Officer

The change to the EDSS does not affect our interim analysis. Our goal for the interim analysis is to reach an enrollment target of 80 patients, and we will conduct the interim analysis just before we reach that target. The key is to get close to that enrollment number, as it will provide us with the most valuable data for the interim analysis. Once we complete the analysis, any expansions of the study will depend on the data we collect. A small expansion could enhance our statistical target based on a strong Phase 2, whereas a large expansion might indicate that the FDA sees potential for registration and would request more safety data and a larger sample size for the study. Did that address your question?

Unidentified Analyst, Analyst

Yes, that's helpful. Thank you.

Pascal Touchon, President and CEO

Thank you.

Operator, Operator

There are no further questions at this time. This then concludes today's conference call. Thank you for your participation. You all may now disconnect.