Atara Biotherapeutics (NASDAQ:ATRA) Q4 2020 Earnings Call

0:00 Good afternoon, everyone. Thank you for standing by, 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 conduct a question-and-answer session, and instructions will follow at that time. If anyone should require assistance during the conference, please press star, then zero on your touchtone telephone. As a reminder, this conference call is being recorded. I would now like to hand the conference over to your speaker today, Eric Heilengren, Vice President of Investor Relations and Finance at Atara Biotherapeutics. Please go ahead, sir.

0:43 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 Tuchon, President and Chief Executive Officer, Dr. Jacob DuPont, Executive Vice President, and Global Head of Research and Development, Upal Kopikar, Chief Financial Officer, Joe Newell, Chief Operations Officer, Dr. A.J. Joshi, Chief Medical Officer, and Kristin Urema, Chief Commercial Officer.

1:42 We will begin with prepared comments from Pascal and Jacob, then open up the call for your questions. We would like to remind listeners that during the call, the company's management will be making forward-looking statements. and Alex Chapman.

2:24 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, TAP-Cell, ATA-188 in multiple sclerosis, and our next-generation allogeneic CAR-T programs. For TAP-Cell, 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 four 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.

3:24 Recall that FDA has already agreed that the non-pivotal studies will be supportive clinical data in the 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 face-free allele data in a clinical Model 5. 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.

4:09 Our plans remain unchanged, that we expect to initiate a rolling BLA and then complete the BLA submission with a clinical module into 3 of this year, once we have the final clinical data required by the FDA. And finally, in Q4, we expect to present data from the Phase III allele study at an appropriate congress. With regard to a TAF cell Phase II multicore study in patients with other EBV-driven cancers, the opening of the clinical study sites is accelerating, and these sites are actively evaluating potential study participants. As a reminder, there are six study populations which may support meaningful label expansion.

4:57 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 TAP cell data in patients with life-threatening complications of EBV viremia were presented at ASH 2020, showing 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 tap-cell inventory, successfully HLA matching 89% of patients eligible for screening in a Phase III allele study.

5:55 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 TAP cell 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 analysis to support TAP cell value story.

6:52 We believe that the unique attributes of PTLD as a serious and deadly disease with no approved therapies, together with TAP cell potential unique benefits as a transformative therapy, support a targeted and highly efficient commercialization model. Regarding TAP-Cell in the EU, which has time designation, our 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 TAP-Cell in EBV-positive PTLD. Recently, we announced we are seeking a partner for the commercialization of TAP-Cell outside the US and discussions with interested parties have started.

7:45 Moving on to ATA-188, a potentially transformational multiple sclerosis program for patients with progressive form of MS. Enrollment is progressing well in the phase two randomized double-blind placebo-controlled study, or RCT, following first patient enrollment in June of 2020. APARA 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 two 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 Ia Open Naval Extension, or OLE, study, as well as translational data from the Phase Ia.

8:48 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 the 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 PD1DNR to improve efficacy, persistence, and durability of response, hence addressing limitations of autologous and other allogeneic RTs.

9:58 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 ATA-3271 our allogenic mesothelin-targeted CAR-T, to parallel studies in multiple tumor types, potentially speeding its delivery to patients and creating shareholder value.

10:45 ATARA will perform IND-enabling studies and process development for ATA 3271. Bayer will submit the IND expected in Q2 or Q3 of 2022 and lead its subsequent clinical development and commercialization. For ATA3219 or allogeneic CAR T for patients with B-cell malignancies, ATARA recently presented exciting preclinical data that Jacob 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.

11:32 Now 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, cash equivalents, and short-term investments. This cash balance includes the net proceeds from the upfront cash payment from the buyer 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. TAPSEL sales, we believe we are sufficiently funded into 2023, inclusive of expenses for the BLA filing and U.S.

12:19 commercial launch of TAPSEL. Reflecting now upon ATARA in 2020, the 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 TAPCEL IA, made significant progress on the TAPCEL regulatory front, initiated the ATA-188 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 step up to support one another during the global pandemic, an incredible internal achievement.

13:15 ATARA's progress in leveraging our unique allogeneic EDVT 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 Jacob. Jacob?

13:40 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 TABSA, 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 Allergenic Cell Therapy Products like TabCell and ATA-188.

14:37 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 TabCell demonstrating consistency of the product's activation profile irrespective of donor activity. and consistent enrichment of receptor-targeting EBV-driven diseases. The study evaluated the in vitro characteristics of TAB cell that help elucidate its proposed mechanism of action. These results demonstrated that upon stimulation, TAB cell exhibits a consistent activation signature at a level of gene expression to cell receptor engagement and secretion of are 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-cell to PTLD patients who had very limited options and can't wait. Continuing with our program, ATA-188 for Multiple Sclerosis, recently we provided an update to our discussions with the FDA regarding the ATA-188 clinical data, the design of the randomized control trial, and potential registrational

16:08 path for this potentially groundbreaking therapy in multiple sclerosis. Regarding the registrational path for ATA-188, 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. Furthermore, 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.

17:03 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 and that statistical power should be allocated to this IA for the sake of rigor. The timing of the IA in the Phase II RCT will be the first indicator 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 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. And thirdly, we can make sample size adjustments to the trial since the IA will occur before enrollment is completed.

18:07 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 Zanville 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.

19:03 EBV-infected B cells and plasma cells can also be detected in the brain of patients with multiple sclerosis, and there have also been reports of elevated antibodies against EBV antigens, such as ABNA1, being associated with more MRI disease findings than that's 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.

19:48 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 ATA-188 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 ATA-2271 and ATA-3271 for the treatment of solid tumors.

20:33 Starting with ATA-2271, 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. ATA 2271 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 ATA 2271 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.

21:27 Now turning to 3271. The first preclinical results of ATA 3271 are allogeneic EBV CAR T cell therapy targeting mesothelin designed for the treatment of solid tumors were presented at CITC recently. Findings from in vitro ATA3271 study shows potent anti-tumor activity against mesothelium in the expressing cell lines and 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.

22:18 In addition, results further support the combined functional design of ATA3271 1XX co-stimulatory 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.

23:04 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 EBVT cells are a promising approach for the treatment of mesothelin positive cancers. Now 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 allocytotoxicity in vivo at the December 2020 American Society of Hematology annual meeting. Preclinical results presented at ASH detail findings from in vivo and in vitro evaluations of ATA3219.

24:21 Specifically, the studies demonstrate potent antitumor activity of 3219 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 3219 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 ATA 3219 to clinical evaluation.

25:06 I would like to conclude by reiterating Pascal's comments of thank you to our ATAR staff, collaborators, patients, and caregivers. We could not have accomplished this much in 2020 without your dedication to bringing these lifesaving therapies to patients. I will now turn the call back to the operator to begin Q&A portion of the call. Operator?

25:59 Hello, operator. Ready to begin the Q&A portion, please. Operator, can you hear us? We're ready to begin the Q&A portion, please. Yes, thank you. At this time, I would like to remind everyone, in order to ask a question, press star, then the number one on your telephone keypad. Again, that is star, then the number one on your telephone keypad.

26:46 We'll pause for just a moment to compile the Q&A roster. We have our first question coming from the line of John Newman with Canaccord. Your line is open.

27:01 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 TABCEL rolling BLA submission, I'm just curious if the agency needs to come to a definitive conclusion as to whether they consider the prior TABCEL 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. And the second question on the mesothelium 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 if they might give us an update early this year or if we will wait for your product later this year.

28:05 Thanks.

28:07 Thank you, John, for your questions.

28:09 Jacob, do you want to take the first one? 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 3 or the CMC module 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 data with data from the 302 or allele 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 TAP cell in the third quarter of this year.

29:25 Thank you. And on the second question about the first-generation academic study that was done with different mesothelin caffeine, Jacob?

29:34 Absolutely. So thanks for the question, John, on the academic mesothelin program. So importantly for ATARA, as you know, and 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.

30:21 Now, we are separate from that program. It's not part of the ATARA partnership, so in essence, we don't have insights into when the colleagues at Memorial Sunket are going to be producing that data, but certainly we look forward to any updates from them.

30:41 Yeah, and we know they're continuing to follow the patient, so one might expect some updates at some stage, but this is not being supported or funded by ATARA. Does it answer your question, John?

30:53 Yes, great. Thank you very much. We have our next question coming from the line of Salim Syed with Mizuho. Your line is open.

31:06 Great. Thanks very much for the questions, guys. Just a couple from me on ATA 188. So, Pascal or Jacob, on the interim analysis that you'll be conducting the first half of 22, 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 some color on how should we be perceiving the different scenarios coming out of the RCT analysis? Thank you, Salim, for your question. AJ, do you want to answer the first question, please?

31:52 Sure. Thanks for the question, Salim.

32:14 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. So this is going to be efficacy, safety, all the general parameters you'd look for. So 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? and we'll try to be as clear as possible once we make any adjustments to design. So once we see the interim analysis, to your point earlier, we've got a robust phase two 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.

33:08 So 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 will all depend on what the interim looks like. But 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, or end of the study, I should say.

33:32 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. So having to increase the sample size to a certain extent is something that will just increase the robustness of these as a phase two study. But as AJ 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 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, would you like to comment on the new data coming for the OLE?

34:26 Sure. And 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 like three-month subcuts. 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? 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 kind of that meaningful two-year readout for all the patients. Okay.

35:01 and we also hope to have some transnational data available by that time from various types of studies that we are conducting on the Phase Ia.

35:12 Great. Super helpful. Thanks, Ajay. Thanks, Pascal. We have our next question coming from the line of Michael Dufour with Evercore. Your line is open.

35:29 Hey guys, thanks so much for taking my question and congrats on the progress. Two questions on ATA 188, if I may. One regarding the change of the primary endpoint from sustainability improvement to ADSS. 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 time 25-foot walk that would have occurred and would have been attributed to SDI are now not possible. And I have a follow-up. Thanks.

36:11 AJ, do you want to take that one?

36:12 Sure. Thanks for the question. It's a good question. Really, for us, the good news for us really throughout the entire Phase Ia 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, as you know, to 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 the study or through the open-label extension, we continue to see EDSS as a driver of improvement.

37:03 Great. Yes, I do. The second question is regarding the interim analysis for 88188. It sounds like after the interim analysis occurs, but before... Thank you. Thank you. Thank you.

37:43 Yeah, 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 kind of align on with FDA is the population target here because we are, as you know, we've got non-active secondary progressive MS and non-active primary progressive MS. We need to kind of align with FDA. Do they want to treat those as separate populations or combined populations? and that's an important piece because for us, we're conducting the study so 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. But in terms of the next steps, this is where it really comes in because once we do the interim analysis, so step one, we expect to align with them over the next couple of months on exactly where they want to go. Then when we do the interim analysis, it allows us after the interim analysis to actually applied for an expedited pathway because the expedited pathway that we're talking about do require you to have a very specific target population.

38:44 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. So that's one key piece that we're going to be doing between now and the interim analysis. And to your point, you were asking about what would now make that interim analysis registrational. One, you need bed alignment. and then two is, you know, 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, you know, how is FDA looking at it both in terms of population dynamic as well as the early results we're seeing on the interim.

39:21 Yeah, and I will add that, as usual, they will also 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 we'd like to see to transform this robust phase two into a regulatory pivotal trial there. So that's a different aspect we'll discuss with them. And that's why we've planned that IA before finalizing the enrollment, because when we say that we'll finalize the enrollment in third part 22, that's for a phase two 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 significant difference versus placebo, You have good safety on your patient, but they would like to see more patients there. And at the same time, there is this clarification on the population.

40:09 Then that allows us to expand that study before it's fully enrolled. By definition, we want to expand it before then. And 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.

40:30 Very helpful. Thank you. We have our next question coming from the line of Anupam Rama with J.P. Morgan. Your line is open.

40:44 Hi, guys. Thanks so much for taking the question. On the APA 188 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 could give us a little color on that. you know, what specific translational analyses we should be focused on.

41:03 Thanks so much. Now, thank you, Anupam, for your question. AJ?

41:08 Yeah, so thanks for the question, Anupam. I think, you know, we've got a variety of different translational elements that we've looked at in the Phase Ia study. We've mentioned previously that we're working on that assay to detect HA-188 in the serum and CSF, and we've conquered kind of the the main technological barriers. Now we're just looking to validate that assay. So that's one component that we might see. There's other things, as you know, in the study that, you know, we had different elements of MRI results and some other biomarkers that we assessed in the Phase Ia 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.

41:56 Thanks so much. Thank you. We have our next question coming from the line of Salveen Witter with Goldman Sachs. Your line is open. Good afternoon and thank you for taking our question. This is Elizabeth on for Salveen. I was wondering if you could talk a little bit more about your commercial readiness plans ahead of the TabCell launch in the first half of Thank you for your question. Kristen, do you want to take that question? 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.

42:48 So that will include a very limited number of highly specialized commercial as well as medical field staff. And then we will be supplementing that with different sorts of communication, multichannel, peer-to-peer, Congress, and so forth.

43:11 Thank you. And I think what I will add as well is that this patient population of PTLD as a first-line therapy is very well identified. I mean, these patients have gone for the transplants. Then they have, unfortunately, been diagnosed with PTLD. They've had their values tested, including EBV positivity of their PTLD. Then they get a first-line treatment, which could be, as you know, rituximab or rituximab plus chemo. and then really they are well identified. So what's important from a commercialization point of view is that at that time the physicians will be aware of TAP cell and be able to plan in advance in case the patient does not respond to first-line therapy or is refracted or is relapsing after response to first-line therapy that they can immediately access TAP cell.

43:58 So this ability to identify the patient early on in their pathway is extremely important in the way we're going to commercialize TAP cells to make it a product that is sufficiently available in a way for the physicians so they know when to act for their patients in the best interest of their patients there. Does it answer your question, Isabelle? Yes, thank you. We have our next question coming from the line of Ernie Rodriguez with Cowen & Co. Your line is open.

44:37 Hi, and thank you for taking my questions also. Actually, my question is also on the commercialization of Capsule. You mentioned thinking about partnerships for the SUS commercialization. I was wondering if you can add any color to that. What are you focusing on those partnerships? Is it focused on the indication on a very particular geography, or how are you approaching it?

45:08 Thanks. Thank you for your question. So in terms of partnering discussion ex-US, we have initiated a number of discussions with interested parties that are really focused on Thank you very much. Thank you very much. to be able to launch that cell in Europe in the second part of 2022.

45:58 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 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 a novel shelf product. So the partners just start to add 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 for that partner in these type of geographies. And in fact, we already have experience of that because we have open clinical sites for Pivotal study and for the 205 study in Europe, so we're already delivering in Europe that cell as we speak to these clinical sites when there is a patient included into a study. We've also opened a Compassionate Use program in Europe which allows to treat patients there.

47:06 So 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 TabCell in Europe. Now, 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. So 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?

47:40 Yes, very helpful. Thank you. Again, in order to ask a question, simply press star, then the number 1 on your telephone keypad. Again, that is star, then the number 1 on your telephone keypad. We have our next question coming from the line of Matt Pitts with William Blair. Your line is open.

48:04 Good afternoon. Thanks for taking my question. Just you 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?

48:21 Thank you, Matt, for your question. Jacob?

48:23 Yeah, absolutely. Matt, thanks for the question. So 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. And so with that guidance, we're also going to be receiving the guidance when it comes to the presentation of the historical non-pivotal data. So it's really connected in point of fact. But our key point here is that we want to get that, secure all of that guidance needed to complete the Module 3 for the BLA.

49:12 Yeah, 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 BTT 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 experts on our product, and the goal of the ongoing discussion is to 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 to 321. But 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.

50:17 Does it answer your question, Mike?

50:19 Yeah, I think so. And then 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, you know, the procedural question?

50:33 Yes, when we're discussing about Module 3, in fact, we are, it's not only a discussion in principle, you know, 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 submit to them data and we discuss about these data and then how do they want to see these data being presented in the final submission. So it's not only a conceptual discussion. It's really a data-driven discussion, which I think is very important to make progress here.

51:07 And maybe one other comment there. For each of these interactions, there are formal briefing books that are submitted in advance of those Type B meetings, but there'll even be requests that come from the agency for additional information that we service to our reviewers over at the FDA. So this is a very rich, very productive, and very frequent engagement that we have with the FDA on this topic.

51:33 And even when we have what we call informal call, the one we had last week, we send 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 or Type B written response there. Great. Thanks. We have our next question coming from the line of Marie Raycroft with Jeffrey. Your line is open. and Mary Raycroft. Your line is open. You may ask your question.

52:22 Hi, this is Ken Chanon for Mary Raycroft. On 188, on whether the current phase two can be used as registrational, is there a, what data does the FDA need to accept in a pooled PPMS versus plus SPMS arm versus running separate trials for the two arms? Thanks.

52:44 Thank you for your question. AJ, do you want to take that one?

52:47 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? So 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 space is identical in both settings. So that's what we're shooting for. Or, 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. So we still need to have separation of ATA-188 versus placebo within whichever population target that they agree to.

53:32 So there's no difference. It's just the population piece.

53:35 And that's why, if I may add, what we say that this Phase II study we are running right now, the randomized controlled trial, is in fact adapted to either scenario from our point of view. And 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. Does it answer your question? Yes, thanks. We have our last question coming from the line of Yigal Natamovic with CD. Your line is open. Hi, this is Carly. I'm for Yigal. Thanks very much for taking our questions.

54:20 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.

54:42 Thank you for your question. AJ?

54:44 Yeah, so the EDSS change does not really impact us at all on the interim analysis, but the goal for the interim analysis is 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. And so 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. And then 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. But Pascal kind of alluded to this before.

55:29 It's a strong phase two. 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 registration. 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.

55:53 Thank you. Thank you for your participation. You all may now disconnect.