Good afternoon, everyone. Thank you for standing by, and welcome to the Atara Biotherapeutics fourth quarter and full year 2020 financial results conference call. As a reminder, this conference call is being recorded. I would now like to hand the conference over to your speaker today, Eric Hyllengren, Vice President of Investor Relations and Finance at Atara Biotherapeutics. Please go ahead, sir.
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 Investors and 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. A.J. Joshi, Chief Medical Officer, and 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. In the fourth quarter of 2020, we advanced very significantly our three strategic priorities, tab-cel, ATA188 in multiple sclerosis, and our next-generation allogeneic 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 a rolling BLA with this module once the FDA decide upon comparability 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 FDA has already agreed that the non-pivotal studies will be supportive clinical data in a BLA submission in any case, and that this procedural decision will just determine whether we provide the data as pooled or parallel analysis with the phase III ALLELE data in a clinical Module 5. We are in frequent and productive discussion with the FDA on the content of CMC Module 3. 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, that we expect to initiate a rolling BLA and then complete the BLA submission with a clinical module in Q3 of this year once we have the final clinical data required by the FDA.
Finally, in Q4, we expect to present data from the phase III ALLELE study at an appropriate congress. With regard to our tabelecleucel phase II multi-cohort study in patients with other EBV-driven cancers, the opening of the clinical study sites is accelerating, these 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-positive AID-LPD and EBV-positive PID-LPD, for which there is high unmet need and a similar mechanism of disease to PTLD. Most recently, new tabelecleucel data in patients with life-threatening complication of EBV viremia were presented at ASH 2020, showing 50%-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 III 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 provider accounts, and performing specific analysis to support 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 potential unique benefits as a transformative therapy, support a targeted and highly efficient commercialization model. Regarding tab-cel in the EU, which has PRIME designation, a pediatric investigation plan, or PIP, was approved in December 2020. In fourth quarter of this year, we plan to submit an EU marketing authorization application for tab-cel in EBV positive 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, a potentially transformational multiple sclerosis program for patients with progressive form of MS.
Enrollment is progressing well in the phase II 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 first half 2022, including efficacy and safety in patients with progressive forms of MS. Following the IA, we expect to complete enrollment of this phase II study in first half 2022. Ahead of the IA next year, we plan to present in second half of 2021 long-term two-year clinical data from the phase I-A open-label extension, or OLE study, as well as translational data from the phase I-A. Recently, we've seen increasing momentum in independent publications and review articles reinforcing the association between EBV and MS, as well as 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 a potential collaboration involving ATA 188. Turning now to our differentiated next generation CAR-T portfolio. Atara CAR-T programs are based on our EBV T-cell platform and our ability to leverage new technologies such as novel costimulatory domains like 1XX, and novel armoring technology like PD-1 DNR to improve efficacy, persistence, and durability of response, hence addressing limitations of autologous and other allogeneic CAR-Ts. In December of last year, we announced a strategic collaboration with Bayer for the development of our mesothelin 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 life-saving cell therapy to patients, and also both parties' prior expertise in mesothelin as an oncology target. 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 tumor types, 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 this asset as best-in-class in B-cell malignancies. Moving on to our financials. With regard to our cash position and runway, we ended the fourth quarter of 2020 with $500.7 million in 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 US tab-cel sales, we believe we are sufficiently funded into 2023, inclusive of expenses for the BLA filing and US commercial launch of tab-cel. Reflecting upon Atara in 2020, 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 our company to deliver on our milestones. In the past year, together, we conducted the tab-cel IA, 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 external milestones doing what we say we will, but the Atara team also stepped up to support one another during the global pandemic, an incredible internal 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?
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 positive 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 life-saving 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 product's activation profile irrespective of donor and consistent enrichment of receptor targeting 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 to cell receptor engagement and secretion of factors associated with effective T-cell responses. We have 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 to 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 in multiple sclerosis. Regarding the registrational path for ATA188, the FDA articulated a preference for an EDSS improvement endpoint and agreed 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. The agency agreed that our phase II 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 disability improvement assessed at 12 months and increased 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 II RCT. That statistical power should be allocated to this IA for the sake of rigor. The timing of the IA and the phase II RCT will be in the first half of 2022. This will include efficacy and safety. Shortly thereafter, enrollment will be completed also in the first half of 2022. We will have a number of options for the IA 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 partnering. Thirdly, we can make sample size adjustments to the trial since the IA 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 New England Journal of Medicine review paper by Zamvil and Hauser from UCSF. This review paper adds new information regarding EBV, and that it may be implicated 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 brain of patients with multiple sclerosis. There have also been reports of elevated antibodies against EBV antigens such as EBNA1 being associated with more MRI disease findings, MS-like cortical atrophy. With The New England Journal of Medicine publication, we find that there is another argument added to the EBV MS hypothesis. 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. 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 our 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 I clinical study. ATA2271 incorporates both a novel 1XX co-stimulatory domain and a PD-1 dominant negative receptor for intrinsic checkpoint inhibition.
Initial phase I 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. Turning to 3271, 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 in vitro ATA3271 study shows potent antitumor activity against mesothelin in expressing cell lines, potency is maintained in the presence of high-tumor PD-L1 expression.
These data support the design of ATA3271 to maintain function in the presence of suppressive PD-L1 expression commonly associated with solid tumor microenvironment, including mesothelioma, non-small cell lung cancer, and other solid tumors. In addition, results further support the combined functional design of ATA3271 1XX costimulatory domain technology in maintaining a memory phenotype while limited 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 antitumor activity and significant survival benefit in mice implanted with mesothelioma cells that highly express both mesothelin as well as PD-L1. This in vivo potency was demonstrated without evidence of toxicity such as allotoxicity.
Both in vitro and in vivo results for ATA3271 suggest that allogeneic mesothelin CAR T engineered EBV T cells are a promising approach for the treatment of mesothelin-positive cancers. Finally, with regard to 3219, 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 antitumor activity both in vitro and in vivo with long-term functional persistence and no evidence of allotoxicity 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 antitumor 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 allotoxicity 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 thank you to our Atara staff, collaborators, patients, and caregivers. We could not have accomplished this much in 2020 without your dedication to bringing these life-saving therapies to patients. I will now turn the call back to the operator to begin Q&A portion of the call. Hello, operator. Ready to begin the Q&A portion, please. Hello, operator, can you hear us?
We're ready to begin the Q&A portion, please.
Yes, thank you. We have our first question coming from the line of John Newman with Canaccord. Your line is open.
Hi, guys. Thanks for taking my question. Congrats on the progress in 2020, especially such a difficult year for everyone. 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 early this year or if we will wait for your product later this year. Thanks.
Thank you, John, for your questions. Jakob, do you want to take the first one?
Sure. Thank you, Pascal. John, thank you for your question. 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 3 or the CMC Module 3 of the BLA. In parallel with gaining the necessary guidance on completing Module 3, we also are expecting resolution to the procedural decision from the FDA as to 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 with data from the 302 or ALLELE study.
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.
Thank you. On the second question about the first-generation academic study that was done with a different mesothelin CAR-T, Jakob?
Absolutely. Thanks for the question, John, on the academic mesothelin program. 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. Those are the ones that Atara oversee in collaboration with our partners now at Bayer.
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. We are separate from that program. It's not part of the Atara partnership, in essence, we don't have insights into when the colleagues at Memorial Sloan Kettering are going to be producing that data. Certainly, we look forward to any updates from them.
Yeah, and we know they are continuing to follow the patients, so one might expect some update at some stage, but this is not being supported or funded by Atara at this stage. Does it answer your question, John?
Yes. Great. Thank you very much.
We have our next question coming from the line of Salim Syed with Mizuho. Your line is open.
Great. Thanks very much for the questions, guys. Just a couple from me on ATA188. Pascal or Jakob, on the interim analysis that you'll be conducting, the first half of 2022, I'm trying to understand what you guys would perceive to be a best-case scenario here, a worst-case scenario, and a middle-case scenario. I know we've sort of touched on this before where you can increase the n a little bit, or you can go large here and is there a futility analysis? Maybe just some color on how should we be perceiving the different scenarios coming out of the RCT, if you increase the n a little bit or a lot or nothing at all. Just a second question on the OLE.
I noticed in the slides that you're no longer presenting first half 2021 OLE data. I'm just curious why that's the case. Thanks so much.
Thank you, Salim, for your question. A.J., do you want to answer the first question, please?
Sure. Thanks for the question, Salim. From the perspective of the interim analysis, this is going to be kind of your classic interim analysis where we spend some alpha to take a look at everything. This is going to be efficacy, safety, all the general parameters you'd look for. In any one of these kinds of analyses, you'd look at everything, right? I think the best way to look at this is from what we do coming out of that interim analysis, you'll have a pretty good idea of where we're going, right? We'll try to be as clear as possible once we make any adjustments to design. Once we see the interim analysis, to your point earlier, we've got a robust phase II study design. A small increase in sample size may be something that we do just to make it a bit more robust.
A large increase in sample size may actually be an opportunity where we're having discussions with FDA, where they're thinking that this can be more supportive of even a larger registrational pathway. I think what we'll try to do is you will see changes we make to the development plan. Hopefully not too many, but it'll all depend on what the interim looks like. We'll try to provide some clarity on it. However, we won't provide the specific data that's coming out of that interim analysis. That will be provided really at the end of the primary observation period. End of the study, I should say.
I could add that the base case scenario for us is that this study is powered to be at the right level for a potential significance between placebo and active treatment there. Having to increase the sample size, to a certain extent, is something that will just increase the robustness of this as a phase II study. As A.J. said, the best case scenario will be really that then we can further increase the sample size to make it one of the pivotal study that the FDA might want to see. 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. On the second question, A.J., would you like to comment on the new data coming for the OLE?
Sure. To your question around the timing of the data, as we've been going through this, you've seen that we've provided data almost at three-month sub-cuts. At this point, it doesn't really make sense to keep dribbling that data out, but we really want to think about it now. What are the meaningful data releases that we're going to have? What's nice about that second half is it allows us to have a full two-year readout on the open-label extension study. That's why we're targeting the second half, is to give kind of that meaningful two-year readout for all the patients.
We also hope to have some translational data available by that time from values type of study that we are conducting on the phase I-A.
Great. Super helpful. Thanks, A.J. Thanks, Pascal.
We have our next question coming from the line of Michael Dufour with Evercore. Your line is open.
Hey, guys. Thanks so much for taking my question, and congrats on the progress. Two questions on ATA188, if I may. One regarding the change of the primary endpoint from sustained disability improvement to EDSS. Does this change that was mandated by the FDA or preferred, I should say, in any way diminish your confidence in the program, given that any benefits in timed 25-foot walk that would have occurred, and would've been attributed to SDI are now not possible? I have a follow-up. Thanks.
A.J., you want to take that one?
Sure. Thanks for the question. It's a good question. Really for us, the good news for us really throughout the entire phase I-A 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. 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, as you know, to 80 patients. You can see it's a very minimal adjustment to account for that change.
Our confidence is high because whether it was in the main 12 months of the study or through the open-label extension, we continue to see EDSS as a driver of improvement.
Mm-hmm. No, great. That was helpful.
Any other follow-up question?
Yes, I do. Second question is regarding the interim analysis for ATA188. It sounds like after the interim analysis occurs, but before enrollment is complete, you're going to have that discussion with the FDA. What do you think the FDA could be looking for in terms of a treatment, EDSS treatment effect, in order to support moving forward and expanding the enrollment of the trial to a registrational study?
A.J.?
I think there's a couple of things that we'd want to do. In terms of one of the big things that we need to align on with FDA is the population target here. We are, as you know, we've got non-active secondary progressive MS and non-active primary progressive MS. We need to align with FDA. Do they want to treat those as separate populations or combined populations? That's an important piece because, for us, we're conducting the study, it really doesn't matter which way they go. We've got it robust enough so that we can either put them together or keep them separate. In terms of the next steps, this is where it really comes in. Once we do the interim analysis, step one, we expect to align with them over the next couple of months on exactly where they want to go.
When we do the interim analysis, it allows us, after the interim analysis, to actually apply for an expedited pathway. Because the expedited pathways that we're talking about do require you to have a very specific target population. That's an important step to apply for expedited pathways, but also from a registrational perspective, you have to have that specific population well identified. That's one key piece that we're going to be doing between now and the interim analysis. To your point, you're asking about what would now make that interim analysis registrational. One, you need that alignment, and then two is, that's going to be really just a question of when the interim analysis comes out and we take a look at those data sets.
How is FDA looking at it, both in terms of population dynamic as well as the early results we're seeing on the interim.
I will add that as usual, they will also like to see, of course, a significant difference between placebo and active treatment. The question will also be about the safety database, how many patients we like to see to transform this other phase II into a regulatory pivotal trial there. That's a different aspect we discuss with them. That's why we planned that IA before finalizing the enrollment, because when we say that we'll finalize the enrollment in third quarter 2022, that's for phase II of the study to then go to pivotal program. Of course, if the FDA aligns with us and they say, on one hand, you have a significant difference versus placebo. You have good safety on your patient, but they would like to see more patients there.
At the same time, there is this clarification on the population, then that allows us to expand that study before it's fully enrolled. By definition, we want to expand it before then. That's why the timing is very important, and we are very well organized to really address that particular timing aspect of first the IA, then the finalization of the enrollment, depending on that discussion with the FDA.
Got it. Very helpful. Thank you.
We have our next question coming from the line of Anupam Rama with JP Morgan. Your line is open.
Hi, guys. Thanks so much for taking the question. On the ATA188 phase I presentation in the second half, you've mentioned a couple times on this call some translational data that'll be presented at the conference. Maybe you could give us a little color on what specific translational analyses we should be focused on. Thanks so much.
Thank you, Anupam, for your question. A.J.?
Thanks for the question, Anupam. I think we've got a variety of different translation elements that we've looked at in the Phase I-A study. We've mentioned previously that we're working on that assay to detect ATA188 in the serum and CSF, and we've conquered the main technological barriers. Now we're just looking to validate that assay. That's one component that we might see. There's other things, as you know, in the study that we had different elements of MRI results and some other biomarkers that we assessed in the Phase I-A study. Some of those may also be possible to present in the second half. Right now we're just putting some of those data together, and it'll be some combination of those elements that we anticipate in the second half.
Thanks so much.
Thank you, Anupam.
We have our next question coming from the line of Salveen Richter with Goldman Sachs. Your line is open.
Good afternoon. 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.
Thank you for your question. Kristin, do you want to take that question?
Yes, thanks for the question. PTLD, as we know, is an ultra-rare disease. Consistent with that, we're really looking at a commercialization approach that's very much in the model of a rare disease model. That will include a very limited number of highly specialized commercial as well as medical field staff. We'll be supplementing that with different sorts of communication, multi-channel, peer-to-peer congress and so forth.
Thank you. I think what I will add as well is that this patient population of PTLD after first-line therapy is very well identified. These patients have gone through the transplants, then they have unfortunately been diagnosed with PTLD. They've had their various testing, including EBV positivity of their PTLD. They get a first-line treatment, which could be, as you know, rituximab or rituximab plus chemo. Really, they are well identified. 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 a factor or is relapsing after response to first-line therapy, that they can immediately access tab-cel.
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 and aware for the physician so they know when to act for their patients in the best interest of their patients there. Does it answer your question, Elizabeth?
Yes. Thank you.
We have our next question coming from the line of Ernie Rodriguez with Cowen and Co. Your line is open.
Hi, thank you for taking my call, my question also. Actually, my question is also on the commercialization of tab-cel. You mentioned thinking about partnerships for the ex-U.S. commercialization. I was wondering if you can add any color to that. What are you focusing on those partnerships? Is it focus on the indication on a very particular geography, or how are you approaching it? Thanks.
No, thank you for your question. In terms of partnering discussion ex-U.S., we have initiated a number of discussions with interested parties that are really focused, first, on Europe, because as you know, we have a very clear line of regulatory pathway in Europe through PRIME designation and our regular interactions with the reviewer there in Europe. We know exactly what is needed there, and we know the timing for submissions now that is planned for Q4 2021. That means this clear regulatory path allows us to have 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 disease in oncology in general, because that's where this partner could really leverage that infrastructure in creating further value with such a 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. The partner just has to have the commercialization and, of course, medical infrastructure there to handle such a product to get access. The delivery and supply could easily be managed by Atara for that partner in these type of geographies. In fact, we already have experience of that because we have open clinical sites for pivotal study and for the 205 study in Europe.
We're already delivering in Europe, tab-cel, as we speak, to these clinical sites whenever there is a patient included into a study. We've also opened a compassionate use program in Europe, which allows to treat patients there. That experience is really at Atara, and we will be looking for a partner that can prolong that experience into the awareness 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 interest. We have already experience in Australia, of course. We are also opening site now in Canada. There are a number of geographies where there is already the possibility to treat patients, and it might be an interest for a partner there as well. Does it answer your question?
Yes, very helpful. Thank you.
Again, in order to ask a question, simply press star, then the number one on your telephone keypad. Again, that is star, then the number one on your telephone keypad. We have our next question coming from the line of Matthew with William Blair. Your line is open.
Hi, good afternoon. Thanks for taking my question. I 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?
Thank you, Matthew, for your question. Jakob?
Yeah, absolutely. Matt, thanks for the question. In essence, as mentioned, we've had a number of productive discussions with the FDA about Module 3, and we really want to secure responses
Regarding the Module 3 and the guidance for the CMC content of the BLA. With that guidance, we're also going to be receiving the guidance when it comes to the presentation of the historical non-pivotal data. It's really connected in point of fact. Our key point here is that we want to secure all of that guidance needed to complete the Module 3 for the BLA.
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. The FDA agrees with us. That's why we are talking in advance, and we have these BTD status that allows us 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 an allogeneic T-cell therapy. The FDA knows that, in fact, we are the expert on our product. The goal of the ongoing discussion is to make sure that we fully align before the submission.
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 321. All this work, all the progress we are making now, are 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, Mike?
Yeah, I think so. Have you submitted any additional data to the FDA, such as maybe comparability assays or something like that since you started having these discussions on the procedural question?
When we're discussing about Module 3, in fact, it's not only a discussion in principle. It's a discussion based on data. We are submitting to them data for the typical Type B setting. We have already had, in the last few months, two Type B meeting on different topics with them on the CMC file where we submit to them data, and we discuss about this data, and then how do they want to see this data being presented in the final submission. It's not only a conceptual discussion. It's really a data-driven discussion, which I think is very important to make progress here.
Yeah, maybe one other comment there that for each of these interactions, there are formal briefing books that are submitted in advance of those Type B meetings. There'll even be requests that come from the agency for additional information that we service to our reviewers over at the FDA. This is a very rich, very productive, and very frequent engagement that we have with the FDA on this topic.
Even when we have what we call informal call, like the one we had last week, we sent to them in advance really a briefing book with all data analysis and details that we think are important to discuss, even in an informal call, which then is different from a Type B meeting, a Type B written response there.
Great. Thanks.
We have our next question coming from the line of Maurice Raycroft with Jefferies.
Hi. This is Ken Chan on for Maurice Raycroft . On ATA188 on whether the current phase II can be used as registrational, what data does the FDA need to accept in a pooled PPMS plus SPMS arm versus running separate trials for the two arms? Thanks.
Thank you for your question. A.J., do you want to take that one?
Sure. It's essentially the same data that we're generating. We're generating one set of data that's driven by EDSS as the disability improvement endpoint. The only question that we're aligning on with them is what population are we looking at. Do we say it's a single non-active progressive MS population? Which, by the way, if you really talk to the thought leaders in the space, that's how they look at this. They think that the progression in this phase is identical in both settings. That's what we're shooting for. Again, if the FDA decides to look at the population separately, they're still going to look at the endpoints in the same exact fashion. We still need to have separation of ATA188 versus placebo within whichever population target that they agree to. There's no difference. It's just the population piece.
That's why, if I may add, what we say that this phase II study we are running right now, the randomized controlled trial, in fact, adapted to either scenario from our point of view. That's great because that allows to have the discussion with the FDA and then the IA, and then to adapt to whatever alignment we have with the FDA there.
Thanks.
Does it answer your question?
Yes. Thanks.
We have our last question coming from the line of Yigal Nochomovitz with Citi. Your line is open.
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? 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.
Thank you for your question. AJ?
Yeah. The EDSS change does not really impact us at all on the interim analysis. The goal for the interim analysis is that we've talked about this, the enrollment target that we have of 80 patients. The way the interim works is we're really going to do the interim analysis just before we hit that 80 patient target. The driver is getting close to that enrollment target more so than anything else. Because that allows us to have the most possible data when we do the interim analysis. Again, once we do the analysis, when you're talking about expansion of the study, again, that'll just depend on the numbers that we get. Pascal kind of alluded to this before. With a strong phase II, a small expansion would be meant to just kind of beef up that statistical target.
A large expansion may signal, for example, the possibility that FDA says, "Hey, this could be potentially registrational. We want a little bit more safety and a bit more total all numbers for your study." Does that answer the question?
Yes, that's helpful. Thank you.
Thank you.
There are no further questions at this time. This concludes today's conference call. Thank you for your participation. You all may now disconnect.