Atara Biotherapeutics, Inc. (ATRA) Q3 2020 Earnings Report, Transcript and Summary

Ladies and gentlemen, thank you for standing by and welcome to the Atara Biotherapeutics Q3 2020 Financial Results Call. At this time, all participants are in a listen only mode. After the speakers' presentation, there will be a question-and-answer session. [Operator Instructions] I would now like to hand the conference over to your speaker today, Eric Hyllengren, VP of Investor Relations and Finance at Atara Biotherapeutics. Thank you. Please go ahead, sir.

Thank you, operator. Good afternoon, everyone and welcome to Atara’s third quarter 2020 conference call. On today's call, members from the Atara executive team will provide an update on our financial results and operational progress and also review our upcoming key milestones and objectives. Earlier today, we issued a press release announcing our third quarter 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, and 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?

Thank you, Eric, and thank you all for joining us this afternoon. During the third quarter of 2020, we continue to make excellent progress in delivering on our strategic priorities, and advancing of free areas of focus, tab-cel, ATA188 in multiple sclerosis and our emerging CAR T portfolio. We are on track to finish the year strong, meeting each external milestone set to date, while progressing on a mission to bring transformative T-cell immunotherapy to patients with serious diseases. I would like to thank very much the Atara staff who have worked so hard to deliver on expectations despite the COVID-19 pandemic. Very significantly, we completed an interim analysis for the tab-cel pivotal 302 study or ALLELE study in the third quarter, achieving 50% objective response rate by independent oncologic and radiopathic review. These objective response rate is consistent with previously published investigator assess data. And the tab-cel safety profile in ALLELE is also consistent with previously published data with no new safety signals. Following these encouraging pivotal interim analysis data for tab-cel in EBV positive PTLD and very productive interactions with regulatory authority, we are now preparing for tab-cel regulatory submissions, and then potential approval and launch. We were particularly pleased to gain clarity on the regulatory package with FDA. Notably, that we can initiate avoiding submission and that we can complete the BLA filing with the elite study currently on all patients with at least six months of follow up for durability of response. We plan to initiate the rolling BLA submission of tab-cel for EBV positive PTLD by the end of 2020. And we expect to finalize the BLA submission in Q3 2021. We are also on track to submit an EU marketing authorization application for patients with EBV positive PTLD in the second half of 2021. Jakob will give you more details about the regulatory updates in a moment. Meanwhile, we are near completion of 13 manufacturing lots that support of commercial validation of scaled up process and we're investing in building the commercial inventory needed for launch. We believe that tab-cel has the potential to transform the treatment of EBV positive PTLD, and offers a compelling value proposition for patients and the healthcare system. Indeed, EBV positive PTLD is an aggressive, often deadly cancer with no approved therapy. The median survival for HCT and SOT patients with PTLD, we are relapsing or referred to as the first one therapy is only two to three months. With tab-cel, the survival rates have been shown in prior studies to be over 80% at two years along responders with fewer treatments related adverse events. In addition, we have been able to deliver tab-cel to U.S. clinical trial patient within three days from our inventory, and we've relatively low burden of administration on the patients and treatment centers. In terms of potential labor expansion for tab-cel, we initiated the tab-cel Phase 2 multi-cohort study in Q3 2020 with the goal of expanding the potential label in PTLD, and closely related EBV driven cancers. I would like to specifically highlight tab-cel potential in additional immunodeficiency associated lymphoproliferative disease beyond PTLD, given the unmet medical need for significant number of such immunocompromised patients, and our new positive clinical data for tab-cel presented at ESMO. I would like now to transition to a multiple sclerosis program, ATA188. We are very excited about the potential for ATA188 to become a transformative therapy for MS patients, bringing clinical benefit not achieved so far with existing therapy. As a reminder, data presented at the Joint ACTRIMS-ECTRIMS Meeting held in September 2020, show that patient with positive NS will achieve suspended in the improvement of AGI with ATA188 therapy at anytime font, maintained it at all future time points and higher proportion of patient short FDI with increasing dose. We will continue to present additional data from an open label extension periodically over the next 12 months. With the next three days of search additional data at the European Charcot Foundation 28th Annual Meeting to be held as of November 15 2020. Additionally, we are increasing our investment to support a given ATA188 international research, manufacturing process improvements and clinical development. In particular, we are advancing as rapidly as possible, the enrollment of patients in the double-blind randomized placebo-controlled trial, which aims at confirming the transformative impact of this new Atara MS. Switching now to CAR T. We believe that we have in exciting portfolio of innovative and differentiated CAR T programs. These programs are based on EBV T-cell platform and our ability to leverage new technologies like 1XX and PD-1 DNR to improve efficacy, persistence and durability of response, and addressing limitations of allocytotoxicity and other allogeneic CAR T. Jakob with detail in a moment the progress we are making in developing these exciting and competitive programs. With regard to our cash position and runway, we ended the third quarter of 2020 with 327.2 million in cash, cash equivalents and short-term investment, which we believe are sufficient to fund plant operation into Q2 2022. At allogeneic EBV T-cell platform has the ability to deliver over shelves therapeutics with potentially transformative efficacy and safety profiles and to produce them at scale, meeting the needs of large patient populations, we believe strongly that these differentiates us from our peers as we are happily progressing on creating value across our three strategic priorities. I'd like to conclude by expressing sincere thanks to the patients, caregivers, collaborators and staff at Atara. We are all committed to delivering on our corporate goals and creating shareholder value. I will now turn the call over to Jakob. Jakob.

Thank you, Pascal This quarter we've made significant progress advancing tab-cel in Phase 3 EBV+ PTLD, for which we've obtained breakthrough designation in the United States, and prime designation in Europe, we conducted the interim analysis and had very productive interactions with regulatory authorities and gain clarity on the regulatory package in both regions. The IA for tab-cel's ALLELE study was conducted in the third quarter, as Pascal noted, we achieved a 50% objective response rate with independent oncologic and radiographic review in patients with EBV+ PTLD following either HCT or SOT. That had reached at least six months follow-up after initial response. This overall response rate is consistent with previous published investigator assessed ORR data. The tab-cel safety profile in ALLELE in the interim analysis is also consistent with previous published data with no new safety signals. During a recent meeting, we presented a comprehensive data package of tab-cel clinical data to the FDA. This clinical package includes the ALLELE interim analysis, Phase 1 and Phase 2 studies with Memorial Sloan Kettering and Atara Phase 2 EAP 201 study and real world experiences from single patient use data. We shared extensive efficacy and safety data with the agency. After productive discussions with the FDA, we now have clarity and alignment on key aspects of the regulatory package to support the BLA for tab-cel in EBV+ PTLD including the points that number one, a regulatory submission is acceptable for the BLA. Additionally, we have completed the BLA submission with the current number of patients enrolled in this study with follow-up for duration of a response of at least six months. And finally, the FDA will consider, as supportive data to the pivotal study the following. The MSK case studies, the 201 study and the real world experience in the BLA clinical module. In a separate recent typing meeting with the FDA, we also had a productive discussion regarding our manufacturing approach for tab‐cel and the CMC data needed in the BLA submission. We remain on track to initiate a rolling BLA submission for patients with EBV+ PTLD by the end of 2020. And we will continue to engage the FDA as part of our rolling BLA and each of this status and expect to finalize the BLA submission in Q3 2021, after having followed for at least six months in responders, amongst already enrolled patients. Following discussions with the prime team, and after EMA approval of the pediatric investigational plan, which we anticipate will occur in December of this year, we expect to remain on track to submit an EU market authorization application for patients with relapsed refractory EBV+ PTLD in the second half of 2021. Finally, data from the pivotal ALLELE study will be presented an appropriate form in 2021. Furthermore, regarding tab-cel, we initiated the tab-cel Phase 2 multi-cohort study in the third quarter and expect to enroll the first patient in the fourth quarter of this year. This study is being conducted concurrently in the U.S. and the EU in order to enrich the evidence base with the goal of expanding the potential label for tab-cel, a therapy believed to provide significant value for those with other severe and life threatening EBV driven diseases. Data demonstrating tab-cel was well tolerated and showed encouraging clinical activity in patients with EBV+ acquired and primary immunodeficiency lymphoproliferative diseases were featured in an e-poster at the European Society of Medical Oncology 2020 Virtual Congress held in September of this year. Specifically, in patients where previous treatment had failed, the objective response rate was 33.3% in AID-LPD, and 37.5% in PID-LPD groups. We also saw several patients with complete responses to tab-cel. Tab-cel was generally well tolerated with a favorable safety profile consistent with previously coverage clinical studies, Patients with PID-LPD and AID-LPD have substantial unmet need and there are no approve therapy for these diseases. Those who relapse or fail to respond to initial chemotherapy have poor prognosis. In PID-LPD especially, there is a need for effective chemotherapy free options, because these patients have an underlying genetic immunodeficiency and often cannot tolerate standard doses of chemotherapy due to the risk of life threatening infection. The multi-cohort study will evaluate both treatment-naive and previously treated patients in six patient populations with significant unmet need, including within immunodeficiency associated LPDs, two cohorts addressing frontline EBV+ PTLD patients as well as two cohorts addressing EBV+ LPDs arising out of primary or acquired immune deficiencies, including AID-LPD and PID-LPD. We look forward to sharing more on this study in coming conference calls. Turning now to our exciting program ATA188 for multiple sclerosis. As most of us know, progressive MS patients remain underserved with current treatment options. Unfortunately, a continued decline of their disease is expected in progressive MS. The current treatment options offer a modest efficacy benefit at best, only delaying progression by a few months. We believe there is tremendous opportunity to develop a transformative therapy to help these patients in need. We have certainly seen early, but encouraging data with ATA188. Recall that we present an important 12 months Phase 1a data for ATA188 at the Joint ACTRIMS-ECTRIMS Meeting held in September of 2020. These data demonstrated that ATA188 was well-tolerated across all four dose cohorts, no dose limiting toxicities and no fatal adverse events have been reported. The safety profile has remained consistent with previously reported data. Importantly, a meaningful number of patients across all four dose cohorts achieved sustained disability improvement or SDI, with a greater proportion demonstrating SDI at higher doses, particularly 42% of patients had SDI in the two highest dose cohorts, namely Cohorts 3 and 4. And once patients achieved SDI at any time point, they maintained it at all future time points. Sustained disability improvement is rare in this patient population and the fact that we have a number of progressive MS patients with this evidence of benefit is very encouraging. Data from the open label extension or OLE part of the study with redosing at 12 months showed that the three patients enrolled in OLE that had SDI 12 months all maintained SDI 15 months, including one patient evaluated 15 months and 18 months who maintain that SDI at both time points. A fourth patient achieved SDI during the OLE at 24 months. We will present additional data on larger numbers of OLE patients periodically over the next 12 months. We also presented at ACTRIMS-ECTRIMS preclinical translational data that further support the proposed mechanism of action of ATA188 which is to target EBV infected B cells and plasma cells in multiple sclerosis. These analyses of the ATA188 T-cells reveal that there is a high specificity of these T-cells defined by their T-cell receptors to EBV antigens known to be expressed in multiple sclerosis. Looking ahead, we will present an e-poster with additional data from the OLE and all four cohorts of European Charcot Foundation 28th Annual Meeting to be held very soon, November 15th to 19th to 2020. With respect to the double-blind randomized placebo control trial, we enroll the first patient in June of 2020aAnd the study enrollment is progressing well, giving an encouraging clinical results to-date in the ATA188 studies and the significant unmet medical need and progressive MS, we are now increasing investment in the ATA188 program. We are expanding the size of the RCT to at least 64 patients changing the primary endpoint of the study to disability improvements. Maintaining biological endpoints to create more opportunity to generate meaningful clinical data and to deliver value. The design allows for the addition of the cohort 4 dose if desired. In addition to measuring disability progression, the study will evaluate other facets of disease including cognition, outpatient ambulatory activity level and fatigue, biomarkers and blood and CSF and MRI imaging. We have submitted material to the FDA, that includes the Phase 1a data, the planned updated design of the RCT study, and potential opportunities for accelerated development of ATA188 for MS patients. We look forward to receiving the agency feedback by the end of this year. I'd now like to provide an update to our CAR T portfolio. As Pascal mentioned, we continue to make significant progress on all fronts. As we noted last quarter, our collaborators at Memorial Sloan Kettering have submitted an IND application to the FDA for our next-generation mesothelin targeted autologous CAR T immunotherapy called at ATA2271. The clinical study has been initiated from MSK, and they are on track to enroll the first patient in the Phase 1 study in the next few months. In addition, we are making progress through IND enabling studies with our allogeneic mesothelin CAR T program called ATA3271, which utilizes the 1XX and PD-1 DNR technologies leveraging our differentiated EBV T cell platform. This 1XX and PD-1 DNR construct is associated with less cell exhaustion, improvements and functional persistence, serial cell killing and in vivo efficacy, which was maintained through multiple tumor re-challenges when compared with first generation CD28, CD23 Zeta-based mesothelin CAR. New preclinical data showed that 3271 demonstrate potent anti-tumor activity, persistence and significant survival benefit without evidence of the allocytotoxicity both in vitro and in vivo, suggesting that allogeneic mesothelin CAR engineered EBV T cells are a promising approach for the treatment of mesothelin positive cancers. These data will be presented at the Society for Immunotherapy of Cancer or SITC 35th Annual -- Anniversary Annual Meeting between November 11 and 14 of this year. Now moving on to ATA3219, a potent next-generation off-the-shelf allogeneic CD19 CAR T utilizing the 1XX technology without the need for TCR editing. We conducted a collaborative and successful pre-IND meeting with the FDA in October of this year and receive feedback to guide the IND filing. IND enabling studies are progressing with a package ready expected to be filed in 2021. And abstract detailing ATA3219 pre-clinical data was accepted for presentation at the 62nd Annual Society of Hematology or ASH Annual Meeting and Exposition being held virtually from December 5 through 8 of this year. These preclinical data of ATA3219 demonstrate persistence, polyfunctional phenotype and efficient targeting of CD19-expressing tumor cells both in vitro and in vivo without evidence of allocytotoxicity in vivo. This will be the first abstract presented at ATA3219. Finally, I'd like to extend my sincere thanking to our staff, collaborators, patients caregivers. We have accomplished much in this quarter thanks to you, and I look forward to providing updates on our continued progress in the near future. I'll now turn the call back to the operator to begin the QA portion of the call, operator?

[Operator Instructions] Our first question comes from the line of John Newman from Canaccord. Your line is open.

Hi, guys. Good evening and congrats on the very interesting data here. Weren't – wasn't expecting an interim this quickly but this is very good. Curious if you could talk at all about the breakout between patients receiving tap cell after stem cell transplant versus patients receiving tap cell after solid organ transplant. Also curious, I know in the earlier studies there were, I think very few, if any patients that experienced relapse after response attempts, so I wonder if you could comment as to what you're seeing there? Thank you.

Thank you, John for your questions. Jacob, do you want to take these two questions, one on the HCT versus SOT, any differences there?

Yes, absolutely. So thank you for the question, John. We have enrolled in the ALLELE study both patients with HCT and SOT previously, and they have received prior therapy as per the protocol characteristics. We have not disclosed the breakdown of the exact number of HCT or SOT patients, but they are both reflected and enrolled in the study thus far. And we have shared data with the agency of both these HCT and SOT patients from the ALLELE study, as well as I mentioned, the historical data from the Memorial Sloan Kettering studies, the expanded access, the 201 study, SPU. And that comprehensive data package includes both HCT patients as well as SOT patients. And I think I will add that in the previews data or the prior studies that we presented, they were indeed some differences that we believe the differences in response rates were not so much linked with differences in the disease itself, but more in specific patients, because the disease is the same. That's why we are really aiming up. Considering that together for the BLA, FDA filing. Of course, the FDA has agreed these can be done. And also, that will require demonstrating sufficient benefit in the combined population, as well as in each goal to fit in. That's the type of data that we bring to the floor to the FDA.

Now to the second questions related to any type of relapse after response to tap cell. Do you want to address that Jakob?

Certainly. So we are, of course following patients on the ALLELE study for any concerns around relapse, and we're following for duration of response as well. And we can turn once again to the historical experience with tab cell, where as Pascal was making reference in the historical data, we see a response rate by investigator of assessment of 50% to 80%, either HCT or SOT. We actually see the long-term durability of response to be quite profound, where we see patients at two years with survival follow-up that we see on the order of over 80% of patients alive at two years. That's in our historical experience. We are certainly going to continue to follow these patients, who are on the remote study. But we feel good about the response rate and the durability of response that these very sick patients gain from tab-cel. And point of reference. And this was mentioned by Pascal, the survival outcome for HCT and SOT patients with EBV positive, PTLD after receiving previous therapy is on the order of two to three months. So the fact that we see the numbers that we see in our historical data, we think is very promising.

Great. Thank you.

Thank you. And our next question comes from the line of Salim Syed with Mizuho. Your line is open.

Great. Thanks so much, guys. Appreciate the color and congrats on the progress. Two for me if I can, wonders following up on the duration of response for tab-cel. Was the six month follow-up duration was that something that the FDA recently communicated to you? Or was this something that was always that was the specific number? And now that and only now you're disclosing it? Or was it something that they looked at in the current data center like okay, six months is kind of the appropriate timeline here? Second question just on the ATA188 program, similarly, on the changing the primary endpoint of the disability improvement, was that done in concert with the FDA? Just a simple yes, no, there, I guess it's fine. And then, just lastly on, the early data that we're going to be getting at Charcot, is that just going to be, again, all patients who are past the 12 month mark? Or what exactly is the kind of data that we'll be -- we'll be getting? Thank you.

Well, thank you. I'll start to address the first question, then Jakob can chime in and then Joe will address the ATA188 question. So clearly, the six months duration of response follow-up that is being asked by the FDA is not surprising, but something we had discussed already with them in the past. And that's why the data we're presenting here from the BLA, the 50%, objective response rate is really in that patients that adds the six months for response. Okay, so that's a 50%. Now, what the FDA is asking now is, to have both the patient have been and also fine and know that we discuss with them in October, when we are the type be meeting to be then followed for six month flowing response. So there is not surprise, not any surprise about the duration of follow-up that is required from the FDA. Jakob, anything to add to that?

Yeah, I think you're absolutely right, Pascal. I think it's a very common request from the agency when you have response rate data for a drug, that six months duration of response is desired. And so as Pascal mentioned, we have this feedback. We've built it into our statistical analysis plans for the illegal study. And we're very much on track in this regard.

Thank you.

Joe, do you want to address the question on ATA188 and the changing primary importance there?

Sure. So thanks Salim. With regard to the primary endpoint, we have changed the primary endpoint in the protocol. And we've actually submitted that protocol as part of the communication with FDA. And we do expect, I think, as per Jakob's commented a little bit earlier, we do expect a response from them this year. And their view on all of the changes we've made to the protocol. But in terms of making that endpoint change, we've already made the endpoint change.

And then there was -- Charcot?

Sure. And for the overlay data, yeah, you're going to see basically, the thing that you will show is just update on all the patients that have that -- we presented, of course, previously, as well as some of the additional patients that enrolled into their open label extension since the last time. So there'll be a significant increase in the number of patients on which we report.

Super helpful. Thanks so much. Yes.

Thank you. And our next question comes from the line of Jonathan Miller with Evercore ISI. Your line is open.

Hi, guys. Thanks so much for taking the question and congrats on all the progress. I'd like to focus in on tab-cel in the multi cohort study. And maybe you could just remind us the timing of some of those different cohorts within the that study and how you would plan to report those cohorts. Then I assumed that the planned EBV positive indication, you teased the possibility in the past, might require additional integrations beyond the Phase 2, would you think it be possible to talk to the FDA about that kind of an gene therapy based indication with those datasets that you have? And then just returning briefly to PTLD? Do you expect if you have to differentiate between HCT and SOT in the label given your prior experience with these two indications and what do you earlier on? Or will those be really wrapped up together?

Thank you, Jon. AJ, you might want to address the first questions on the medical standing with some cohorts and then Jacob will address the next two.

So from the – sure. From the timing perspective, we've opened up the AID-LPD and PID-LPD cohorts as well as the cohorts on EBV positive leiomyosarcoma. The ones that we're holding off on just a bit from a timing perspective are the PTLD cohorts. Though they don't directly compete with the 302 study, there's always a theoretical possibility. So we want to hold off on those until we're complete on the 302, but the other cohorts are open.

Yeah. And I think, the data we expect to come first will be from the two cohorts with more patients by definition, addressable there, which are the AID and PID and that's about that we believe could come as early as 2023. Jacob, do you want to address the questions on how we want to discuss with the FDA potential EBV indication or indication for all EBV related cancers?

Absolutely. So thanks. Thanks, Jonathan for the question. So we believe in the multi cohort study that each one of the distinct populations, each of the cohorts represents a distinct opportunity for a regulatory filing, so that that's the stage. But we also recognize that, with the eventual approval of tab-cel in PTLD, and then adding on the additional cohorts that there's this mounting of information that if you have an EBV power positive cancer, that tab-cel provides benefit for you. So that certainly provides the opportunity for a tumor agnostic label where again, we have a diagnostic test, to show EBV positivity. And then, we have a specific therapy, namely allogeneic EBV T cells that can target that particular abnormality in the tumors, so we think this is ripe for a tumor agnostic indication. And certainly, as we generate data, not unlike we did with the ALLELE study, we're going to look for opportunity to share the data with the FDA, and to engage upon potential regulatory filings, either with individual cohorts or as the date amounts with a more tumor agnostic label. And to your last question, I think the -- as I said earlier, FCT and SOT will be considered together for the BLA filing. The FDA has agreed that this can be done. And we will also ask for sufficient benefits in the combined population as well as in each cohort separately. This was by the way, also the indication of obesity status to look at that in a combined way there. So meanwhile, we'll be continuing to have discussion with the FDA regarding how this patient population will be addressing a potential label. And we'll communicate that feedback at an appropriate time. Does it answer your question?

Yeah, absolutely. Thanks a lot guys.

Thank you. Our next question comes from Ben Burnett from Stifel. Your line is open.

Great. Thank you. And I'll add my congrats to the data as well. Just a one first question on just kind of the safety profile and you think you can give on that, just given that this is a partially HLA match product. Did you see anything that was surprising in terms of graft versus host disease formidable there? And then also, just given that this is a T cell product, did you see anything in terms of CRS or neurotoxic or you've seen some in certain CAR-T studies? And then if you don't mind, I have one follow-up.

Yeah. Jakob, do you want to take that one?

Yeah, certainly. So Ben, thanks for that question. This is, as noted a partial HLA match product. And we've spoken about the potency and the efficacy that we see there, but that comes actually with a very good safety profile, we have not seen any CRS with this therapeutic, we have not seen any neurotoxicity, we have not seen any treatment related mortality. And recall that this is actually a therapeutic, which has quite a lot of clinical experience between obviously the ALLELE pivotal data that we're just describing for you today. But also the Memorial Sloan Kettering Phase 2 experience, our Phase 2 trial, the two month trial, as well as the single patient use and expanded access experience. So we have quite a lot a large safety experience. And I think we can say throughout that, that we really have a very acceptable safety profile, excellent safety profile. And to your question, we don't see any of those serious effects, either CRS neurotoxicity or treatment related mortality. And recall that this is an off the shelf therapy where we can deliver this to patients within three days. So we think that this is quite meaningful for patients.

As well as -- I will insist on the fact that if you think about our platform of this partially HLA matched therapy, the ATA188 altogether within -- with our academic partners, our sales now at Atara, we have treated several hundred patients, about 300, we believe, in total there since the beginning. And that means that we have a very strong safety database there in terms of -- and very comprehensive safety database in terms of all the patients that have been treated with these partially HLA-matched T-cell therapy. So we feel confident about having a very good profile to be discussed with the FDA once we initiate the BLA. A – AJ Joshi: And maybe just one final point, just to underscore than in the pivotal of OLE data cells. We did not see any new safety signals either. So that also increases our confidence.

Okay fantastic. That's super helpful. And if I could just ask one about your experience with the manufacturing and supplying tab-cel in the earlier Phase III study, it was a multicenter study. So I guess, what was the timelines for delivering tab-cel to patients? I guess you have an average number there. And were there any patients who didn't get product because of a proper HLA match? Thanks so much.

Thank you for the question. The answer is no. But maybe, Joe, you want to add a few colors to that in terms of experience in delivering that sale within a few days to patient?

Thanks Pascal and Dan thanks for the question. Our delivery response times and delivery to patients have stayed relatively consistent prior to COVID and during COVID, which I think is quite an a testament to our overall platform architecture and our ability to get a tab-cel to patients quickly but easily within three days domestically and we also have had -- we have dropped no shipments whatsoever during that period of time. And quite honestly, we've actually seen performance even get better recently. So from that perspective, very consistent, quite a validation for our delivery portion of our supply chain and quite a compliment to the efforts made by the supply chain team here at Atara and the clinical sites that we support.

Understood. Okay, and if Pascal, if I understood you correctly, you said there were no patients who didn't get product because of improper HLA match?

I think we have been able to enroll all the patients with proper matching there that we could deliver to them. As you know, in terms of the inventory rebuilding plan at this time of commercial stage is to cover over 95% of the total patient population. We offer our lines for tab-cel.

Got it? Okay. Thanks so much. Appreciate it.

Thank you. And our next question comes from the line of Marc Frahm with Cowen. Your line is open.

Thanks for taking my questions and congrats on the data this evening. Maybe firstly, since the interim was taken in August, 6 months the product would follow imply that you'll have that in roughly February. It's to -- what -- is that the rate limiting step in the turnaround to Q3 completing the BLA is just the time you need to turnaround the 6 month follow up into submission or there are other things that are also limiting how quickly you can complete the rolling BLA?

Yeah, I will start and Jakob you might want to chime in there. It was something that in the Q3, when we did the IDA, we had a certain number of patients with that 6 months for response there, that's the group of patients for which we couldn't be 50% of our response rate or objective response rate. Now, at the time of the discussion by the meeting with FDA that was in October, we had all the patients that have been an all and what the FDA got in basically throughout the duration of follow up for the response for this patient as well. So that's why you then end up into this Q3 from Q1 completion of the submission. Jakob, anything to add?

Yeah. And I just want to underscore also the rigor of the process. So we mentioned the 50% response rate of the interim data. And that was by IORA, so independent oncologic and radiographic assessment. So there is this additional step where we provide this data to an independent authority that analyzes not only the images but also the patient histories and cases. And then, we get this independent assessment, which is really apart from Atara, and that additional step takes a little while. So again, as we look at the overall span of the BLA filing it, as we said we're initiating the BLA here is our plan in December, and then we'll have the data cut then we'll do the full analysis with the independent authority, and then we will put -- we’ll will analyze the data and put it all together in the clinical module. Meanwhile, we're also putting the other aspects of the following together the CMC module and these other things. So that's one of the advantages of the rolling BLA, that we're also going to be undertaking is that we can take the systematic approach with the rolling BLA and also because of our BTD status really ensure a complete robust and successful filing.

Great, thanks. It's very helpful. And then, in your prepared comments, you mentioned having a second meeting with the FDA around the CMC issues. Given complete agreement now on exactly what assays you need to submit for things like compatibility, or is there still some discussion with the FDA to have there? And then, if you do have the full agreement, do you have all that data in hand already or are there still the tests that need to be run.

Yeah, I’ll start and Jacob might chime in there. I think we have good progress in discussing the CMC module, and we’re making good progress there. At the same time, we also -- and Joe might want to chime in as well, we are testing these batches, the slots that we are making for the commercial stage. And we just need to finalize that we’re posting very well to be able to finalize the CMC model. But, we've got clarity already from the FDA, and we’ll continue to discuss with them, as part of the BTD and as part of our rolling submission. Jacob, to start with, and Joe, if you have anything to add, but Jacob to start.

Yeah. I think that's really true. And I mean, this is -- and Joe can articulate further. But this is an ongoing dialogue that we have been having and Joe and a number of experts here at Atara. With the FDAs around CMC, and I think we've made a lot of progress on the understanding of what needs to be in the BLA. So I think we're feeling quite good about the progress. But Joe, you can probably speak more specifically to the assays that was, the nature of the question that Marc asks.

You bet. Thanks for the question Marc. Yes, as Jacob mentioned, and Pascal, ever since I've been here, three and a half years, we've really been in a very good collaboration with the FDA about developing and validating the assays to demonstrate capsules potency and how the product works in accordance but it’s a stated mechanism event. And so from that perspective, there's been an outstanding connection with them. They're aware of everything that we have done to support that. In addition, a big part, as you all know, Module Three is the Process Performance Qualification aspect. We've completed all activities associated with that, including testing. And we're clearly just finishing up the final report that will be a part of the submission. So from our perspective, good representation of our collaborative approach with the FDA, testing looks very solid, and I think we have a very strong and in front package that we're confident will land us in the right position.

Okay. Thank you very much.

Thank you. And our next question comes from the line of Yigal Nochomovitz with Citi. Your line is open.

Hi. This is Samantha on for Yigal. Thanks very much for taking the questions. And I'll add my congrats on the data. Just first, are you able to tell us how many patients were included in the interim analysis?

Jakob?

So at this stage, we are not counting the number of patients that were in the interim analysis. We, as mentioned are in discussions with the FDA and we have enrolled a number of patients currently that will form the basis of the clinical data in that BLA filing, but we are not currently commenting on the sample size.

Okay. Understood. And then presumably you're continuing to enroll, because you haven't enrolled all 66 patients. I understand you're not going to have six months durability data for all of those patients. So would you -- are you considering including those incremental patients in the this ORR analysis for the BLA?

Jakob?

Yeah. Thanks for the question. So yes, we continue to enroll patients in the ALLELE study. But as I mentioned, this is despite the fact that we have enrolled the number of patients required to provide the necessary number of patients for the BLA filing and we'll get the durability of response to complete the BLA, but we think that the additional patients enrolled give us further data during the expected BLA and market authorization review process that further support subsequent discussions with payers as well. And we also will continue to receive demand for tab-cel through our EAP, which can lead to opening of new sites as well. So we think the right thing to do is to continue to enroll patients on the study and the EAP to provide that for patients. But as mentioned, we haven't rolled the number of patients required for the BLA submission.

So just to be clear, again, there, we don't need to enroll more patients to finalize a BLA submission the clinical module, we just need to add the follow-up for the currently enrolled patient, but we've decided to continue the enrollment as we’ve been say to extend the database for the use and also to make sure that we can offer access to patients in need.

Okay. Understood. That's helpful. And then just switching to ATA2271, the phase 1 trial that's going to enroll the first patient this quarter. Can you give a little bit more detail on that phase 1 trial? Are you targeting a specific tumor-type or will be all tumors that express mesothelin. And are there certain cutoff for mesothelin expression that is required for study entry?

Yes, this is an advanced mesothelioma trial. And Jakob, do you want to comment from specific cutoff on mesothelin entry?

Yeah. Absolutely. So this is really utilizing the pathology lab tests for mesothelin at Memorial Sloan Kettering. So this is an IHC immunohistochemistry test that's being utilized. And so they're using standard path lab IHC metrics for that inclusion criteria.

Okay. And then just last one for me. Is there any reason to believe that 2271 wouldn't work and other tumors that express me as mesothelioma or do you expect this to be targeted specifically to mesothelioma?

Yeah. This is Jakob, again. So we do believe that ATA2271 and the allogeneic ATA3271 would certainly have potential in a number of other solid tumor types. And so we certainly are initiating in mesothelioma. But you can think of a number of other solid tumors, including pancreatic cancer, non small cell lung cancer, ovarian cancer, and a number of others were mesothelioma – mesothelin rather, is over expressed on those tumors, where this type of potent CAR T therapy could provide benefit for patients. So our intention is certainly to explore both of these cell products in wider populations beyond simply me, mesothelioma.

Okay. Great. Thanks for taking the question.

Thank you.

Thank you.

Thank you. [Operator Instructions] Our next question comes from Matt Phipps with William Blair. Your lines open.

Good afternoon. Thanks for taking me. Congrats on the intern and FDA clearance here. Do have one question in the 10-Q just filed, there's an added line saying that based on an interim, a post-marketing requirements maybe I guess added. So is that based on any feedback from the FDA on any post-marketing requirements after this interim analysis, or maybe EMA?

Thank you for that, Matt. No, I think it's not based on the specific discussion that we have on that, its just a typical type of situation that when you have a submission based on some interim data there, and then they might be some additional ask in terms of commitment. So wanted to make sure that, it is clear that, there is no specific discussion about that that took place either with the EMA or the FDA.

Great. That's good. Thanks. I guess, follow up on the novel 1XX CAR. I know, I guess original academic version that being conducted in MSK also started to look at IV delivery. I don't believe there's been any presentation of that data. I know you guys are starting out with the Intrapleural Infusion but just curious, I guess, if you know, we'll get any update from an IV delivery of the first- novel 1XX CAR you plan to eventually look at IV as well?

I think what's happening that the first-gen is an academic program, as you know is not another problem there as one that is being pursued by MSK and they were probably wants to continue to make some presentation of data when the data are maturing they at some stage. But this is not Atara program, whether for 2271, which is Atara program as well as 3271. In both cases, we intend to go beyond the entire peritoneal administration that has been used in advance mesothelioma trail and to study the CAR T. So in both cases, we will start in advanced mesothelioma, for example, with 2271, with an IPO followed by an IV. And then of course, for 3271, we believe that this particular construct due to the benefit of not only the one x factor, because the mesothelioma and the PD-1 DNR, but also the EBV T-cell, and their natural biology in terms of trafficking, and persisting, we believe that the teaching the code is going to be the second goal to study with that particular compound.

Okay. Thanks, Pascal.

Thank you. And our next question comes from Anup Rama with JPMorgan. Your line is open.

Hi, guys. This is Tess in the call for Anupam. Just one from us on the MS side of things. You are planning meeting with regulators by the end of this year for ATA188. I guess, can you maybe describe for us what are the range of regulatory scenarios that we should be considering with those discussions? Thanks so much.

Thank you. AJ, do you want to take that one.

Sure. Thank you for the question. A couple of key things that we were waiting for feedback from the month. Part of it we've already talked about the changing the endpoints, we'll get feedback on our change endpoints and we'll get feedback on the time points that we're considering. We've talked in the past about 12 months versus 15 months' time points based on some of the data that we're seeing in the Phase 1a, as well as the open label extension of the study. And then when you think -- and then I'm assuming you're also then talking about the scenarios on what are the next steps with this program? And it's hard to speculate on those things we are discussing with them really all the different potential expedited pathways, because we do feel like the program prequalify for really several of them. And those are things like fast-track, breakthrough, and arm at. So, we expect to receive feedback, a specific feedback on every one of those pathways from the FDA.

Does it answer your question?

Great. Yes, that's great. Thanks so much for taking our question.

Thank you.

Thank you. And our next question comes from the line of Maury Raycroft from Jefferies. Your line is open.

Hi, everyone. Congrats on the progress and thanks for taking my questions. So, the first one is on the OLE program, just wondering if you can say how many sites are open currently? And how many additional sites you so plan on opening overtime?

Thank you, Maury. AJ, do you want to answer the question?

Sorry, so just to be -- just to make sure I have your question correctly. You're asking me about how many more sites we're looking to open? I didn't catch that correctly.

How many are open and then how many more you plan on opening?

Got it. I believe we have something around in the mid-40s of sites open and the main areas that we're going to be continuing to have the site activity -- site activation activity will probably be in Europe at this point, because we mentioned to you before that we've opened up Europe, we're seeing demand there from an expanded access perspective. So, as Pascal alluded to, we want to make sure we're able to kind of meet the needs of the patients there. And it's always best to do that through a study environment than an extended access environment. So, that's where you'll probably see the majority of any other increases. But we've got plenty of sites open up and running and we just want to keep you know, keep that access pathway open for patients as much as possible.

But just to be clear, we don't need to increase significantly the number of new sites. We just adding the site that are open today and some that are in the process of being open. And as AJ has said, Europe is very important in many aspects in terms of addressing specific patient needs and also gaining experience with that setting you up there and we are recently not only the first competition accused that we are there for some time, the recent deals showed the first patient enrolled in the OLE study in Europe. So that's great to create that base of experience which you have confirmed with -- in anticipation of future submission and launch in Europe.

Got it. That's helpful. And then for the PTLD study, if you can talk about time to response in the phase 3 versus the phase 2 in the EAP studies, and how often did you read those and switch haplotypes and what have you learned based on?

Jakob, do you want to take that one.

Yeah, absolutely and AJ, can also contribute some information potentially. So, as we mentioned in the beginning, these PTLD patients who've had prior therapy, either after HCT or SOT have a very short survival on the order of two to three months. So in the context of that, you really need a rapid response. So if you look at the academic data Memorial Sloan Kettering in phase 2 and so forth. We really do see a response that occurs on the order of weeks. And that's really important because these patients have a very, very short survival. So I can't comment on that aspect for the ALLELE study. We're only disclosing today the 50% response rate by IORAs, IORA rather and the safety profile, but I can articulate those aspects of the historical data, anything further to contribute, AJ?

No, I think just to underscore, Jakob’s point, we're not going to give specifics on that at the end of the day. This is a rapidly progressing disease. So you can Intuit that, in order for therapy to be successful, you're going to have to have a relatively rapid response.

And in term of which type of switch therapy any particular comment, AJ?

Yeah, I think at this point, we're probably not going to be very, very specific on any switch at this time. I think just overall, probably a good overall statement for you is we're really not seeing anything that looks different from what we've seen in the prior MSP experience, from those two perspectives.

Got it? That's very helpful. Maybe last quick question. For 188, have you had a chance to look at the 15 month data for the additional two patients in cohort three to inform the final dose in the randomized control study?

I mean, let's wait for the Sachs presentation in a week time.

Got it. Okay. Thanks for taking my questions.

Thank you. And our next question comes from the line of Salveen Richter with Goldman Sachs. Your line is open.

Good afternoon. Could you help us understand what is given to the variability with your data for tab-cel or to range from 50 to 80%? And then secondly, have your projections on the commercial opportunity for tab-cel in EBV positive patients changed here, as you run conducted these clinical trials and if you could just remind us on what they are? Thank you.

Thank you. Maybe to address the first question, Jakob and Kristin might address the second one.

Yeah. So Salveen, thank you for the question. When I look at the data this, especially having seen the interim analysis on ALLELE, a thing that actually impresses me is if anything, the consistency of the data. So I do think again, the safety profile is very consistent with what we've seen with the previous studies. And as Pascal mentioned, we've now treated near 300 patients with this therapy between the collaborators in our study. So I think there's deep consistency there. I also think we see consistency in terms of the rapidity of the response and the magnitude of response, now you have to -- I think your point is well taken about 50% to 80% response rate, I still would categorize this as very robust response rate. And I think that's reflected also in the two-year survival when you look at the historical experience. Now with the ALLELE study, that's obviously a registration intense study, where we have really tightened up the eligibility criteria in order to produce an experiment that's going to be convincing to regulatory authorities to give us approval. So I think, when you think about the number of prior lines of therapy, the biomarker positivity, the performance status of the patient and all of those things, those are really tightly controlled within a study like ALLELE. And so the fact that we're getting a response rate here and the other characteristics of the performance of the therapy, which is very similar to the historical experience gives us great confidence. Now, I will say and remind that the 50% to 80% response rate in the historical experience in our investigator reads, and what we're reporting today is the independent radiographic and oncologic response rate. So there is a little bit of a different way to read this. But, obviously, the data in the ALLELE study is a more robust experiment, not only from a patient enrollment standpoint, but also from an efficacy standpoint, where this is independently assessed, and frequently, what you see with independent assessment is response rates go down, if anything, but I will say here, that the 50% response rate on the interim is very robust data point.

Okay. Thank you.

Kristin, do you want to answer the question about how do we see the commercial potential there?

Yes, thank you, Pascal. And thanks for the question Salim. So we're right where we thought we would be and where we want to be in terms of the commercial assessment. So, just heard Jacob, kind of reiterate our interpretation of the data, and I would just add that profile is entirely consistent in how we've been thinking about what would represent a commercial opportunity for tab-cel. So we continue to believe that there are several hundred patients in the U.S. who will benefit from this therapy. and the value proposition for tab-cel, is, we believe very strongly between the response rates, the historical survival data that we've seen, of course, that's historical, but we'll be watching very carefully to see how that evolves with ALLELE. And I also would like to emphasize, the truth is its a very convenient therapy to deliver and for patients to take, and we've heard about the safety profile and how that's being established, our ability and expectation to cover the needs of over 95% of patients at the time of the launch. And pre-treatments are not required and it's a very simple patient -- very simple therapy with an IV infusion, five to 10 minutes, two hours of monitoring. And in the course of our study, we've seen patients treated in a variety care settings as well. So we continue to be very confident in the commercial opportunity for tab-cel.

Thank you.

Does this answer your question, Salim?

Yes, thank you Pascal.

Thank you.

Thank you. And our next question comes from the line of Tony Butler with ROTH Capital. Your line is open.

Thanks very much. Just a very brief question around statements made on ALLELE, about robust end points of 50%. I'm very respectful for that. If you look at the expanded cohorts in 205, and I'm just curious if you could say the same for 33% to 37%, I recognize that's a tremendous benefit over standard of care, but would you claim that to be robust, as well. And second on 188, with 60 patients in the Open Label Expansion? Are patients could - -are they could do -- are patients being continuing to be enrolled today, in that Open Label Expansion? Would you expect more patients to continue to enroll? I mean, I might have thought so you have 13 sites out? I would just think that there would be a good number of patients who would want to be enrolled in that in that expansion cohort? Thanks very much.

Yeah, absolutely. So Tony thanks for the question. First and foremost, these patients with PID-LPD and AID-LPD, they really have a substantial unmet medical needs. So again, these are patients who have failed available therapies and there really are no approved therapies for these patients at all. And so I think the other point is that when you have a patient who's got an acquired immunodeficiency or an inborn immunodeficiency giving these patients cytotoxicity chemotherapy can actually be quite dangerous in terms of putting them at risk for getting infection and so forth. So I think that, you know, with the very high unmet need, with the absolute lack of approved and available therapies for these patients, and then looking at, you know, this type of a chemo free option for these patients, that's not going to suppress -- their immune system further. And then achieving response rates, you know, on the order of 33% to 37.5%, we think is actually a meaningful result for these patients. And so I think this is clinical benefit for these patients, absolutely.

Thank you. And AJ do you want to answer about the number of patient we expect orally and online.

So just to add a bit of clarity, it's in -- the open label study is exactly an open label extension. So really the only people that were enrolling in that study are people from the four cohorts that we've described previously. So really looking at 24 maximum potential patients that would go into that study. And for that purpose, really apart from one patient who moved out of the country and a couple of patients in the earliest cohorts, who were we had not actually decided on the right dose to move forward to the open label extension. So then they moved on to other therapy. Probably everyone else has declared their interest in moving forward into the open label extension. Any new patients that are interested in study, we really want to actually move them into that randomized control trial, as you might imagine.

Absolutely. Thank you very much.

And maybe one other comment to make is, as we've reported, you know, we in the ALLELE at ACTRIMS-ECTRIMS we presented a handful of patients there. But as Pascal and I have articulated, there's going to be more data that's going to be presented over the next 12 months or so. So you'll see data for more patients go going forward as well.

Thank you. Our next question comes from Michael DiFiore with Evercore ISI. Your line is open.

Hi, guys. Thanks very much for taking my question. I just wanted to follow up and dig in a little bit more on ATA188 for IMS? It's already been answered. It sounds like the incremental data on cohort 4 patients Y and Z and how they did at 15 months could be presented next week. But I just want to – I'm curious, why didn't even top line it today because it sounds like you're still undecided on whether to add the cohort 4 dose to the randomized control portion of the trial. And that's one question. And as a follow up to that, if you could just remind us on the status of your discussions with the FDA, in terms of exploring possible accelerated approval possibilities and whether they've occurred yet. And if cohort 4 patients Y and Z did not show sustained disability improving at 15 months, I'm very curious to see how it may impact future discussions with regards to accelerated approval pathways. Thank you.

Thank you, Mike. And I’ll start answering the beginning of your question and AJ will give you more detail on the regulatory discussion there. I mean, we have the data, we have made the decision for getting the doors, which are going to announce that next week because we are protecting the embargo from short on the data. So just to be clear, so you just have a week to wait AJ any comment on the – on the regulatory interactions?

Yeah, just from the from the timing perspective, you know, as we've given, we've actually had communication with FDA. We've submitted in fairly significant detail, the protocol and a variety of questions that we have really around all of those expedited pathways that we talked about. We do expect response from them by the end of this year on that. So we would presume that we would probably communicate that to early next year.

Great, thank you very much.

Thank you, Mike.

Thank you. And ladies and gentlemen, I'm not showing any further questions at this time. It is now my pleasure to close the call. Thank you for participating. You can now disconnect.