Atara Biotherapeutics, Inc. Q2 FY2020 Earnings Call

Ladies and gentlemen, thank you for standing by, and welcome to the Atara Biotherapeutics Second Quarter 2020 Financial Results Conference Call. Please be advised that today's call is being recorded. I would now like to hand the call over to Eric Hyllengren, Vice President 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 second 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 for 2020. Earlier today, we issued a press release announcing our second quarter 2020 financial results and operational progress. This press release and an updated investor presentation are now available in the Investor & Media section at atarabio.com. Joining me on today's call are Dr. Pascal Touchon, President and Chief Executive Officer; Dr. Jakob Dupont, Executive Vice President and Global Head of Research and Development; Utpal Koppikar, Chief Financial Officer; Joe Newell, Chief Operations Officer; Dr. AJ Joshi, Chief Medical Officer; and Kristin Yarema, Chief Commercial Officer. We will begin with prepared comments from Pascal and Jakob, then open the call up for your questions. We would like to remind listeners that during the call, the company's management will be making forward-looking statements. Actual results could differ materially from those stated or implied by our forward-looking statements due to risks and uncertainties associated with the company's business. These forward-looking statements are qualified in their entirety by the cautionary statements contained in today's press release and the company's SEC filings. These statements are made as of today's date, and the company undertakes no obligation to update these statements. Now I would like to turn the call over to Pascal. Pascal?

Thank you, Eric, and thank you all for joining us this afternoon. As we know, we are all living and operating day to day amid a global pandemic, never seen before in our lifetimes. And yet at the same time, we at Atara remain committed to serving the patients in need and delivering on expectations. Our mission indeed is to improve patient lives, and we are focused on bringing transformative therapies to those in need. We have an even stronger commitment and resiliency. To date, we have seen a relatively limited impact of the COVID-19 pandemic on our business. We have worked with our clinical trial sites to implement remote study visits, leverage telemedicine, home health care, and other methods to ensure continuity of care for patients and to preserve key endpoint data. From a supply chain perspective, we continue to deliver product to patients from our inventory on time, which is a clear advantage of our off-the-shelf, allogeneic EBV T cells. Most importantly, we remain on track to initiate a BLA submission for tab-cel for patients with EBV positive PTLD by the end of 2020, with more details to follow in this call. The COVID-19 pandemic is continuously evolving, and going forward, we will closely monitor the situation and continue to assess its potential impact on our business and operations, including the timing and execution of clinical and preclinical studies. During the second quarter of 2020, we continued to make tremendous progress in delivering on our strategic priorities, tab-cel, ATA188 in multiple sclerosis, and our emerging CAR T portfolio. Starting with tab-cel, as I mentioned, we remain on track to initiate the BLA submission by the end of the year. As the next step, we will conduct an interim analysis of the Phase 3 study in the third quarter of 2020, and then discuss the totality of tab-cel data with the FDA in a pre-BLA meeting, after which we expect to initiate the BLA submission if the FDA is supportive. 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 very importantly, health care systems. As a reminder, relapsed/refractory EBV positive PTLD is an aggressive and deadly cancer with no approved therapy, and median survival in the HCT and SOT populations is only 1.7 and 3.3 months, respectively. With tab-cel, to date, we have seen a high and durable treatment effect with few treatment-related serious incidences. In addition, we expect to be able to deliver tab-cel to patients in need within 3 days from inventory, and we have a low burden of administration on the patients and treatment centers. If confirmed, the pivotal study such a compelling value proposition could lead to significant business potential for tab-cel’s first indication. In terms of potential label expansion for tab-cel, we remain on track to initiate enrollment in the second half of 2020 in a Phase 2 multi-cohort study with the goal of expanding tab-cel's label in PTLD and closely related diseases. We will focus on extending further into immunodeficiency associated lymphoproliferative disease or IA-LPDs, given the commonality of the EBV driven mechanism of disease in immunocompromised patients, high unmet medical need, and positive clinical data to date with tab-cel. We are very excited about this potential opportunity for tab-cel as these populations represent altogether an additional few thousand patients with serious and addressable EBV driven diseases in the U.S. alone. Therefore, to maximize tab-cel’s business potential, our near-term focus will be the successful initiation and fast enrollment of this multi-cohort Phase 2 study on top of the planned initiation in EBV positive PTLD by the end of this year. Now, moving on to ATA188 or EBV T-cell immunotherapy for multiple sclerosis. We strongly believe in the potential for ATA188 to become a transformative therapy, improving the lives of MS patients. There remains a significant unmet need, particularly for progressive MS patients, with approximately 1 million patients living with such a progressive form of the disease. Patients and caregivers are in need of new approaches with novel mechanisms of action in order to truly improve clinical outcomes and reduce disability. We believe ATA188 could have the potential to be such a therapy, creating tremendous value for patients, health care systems, and our shareholders. Beyond tab-cel and ATA188, we are also creating potential value through an exciting portfolio of innovative and differentiated allogeneic CAR T programs. These are based on our EBV T-cell platform and our ability to leverage new innovative technologies like 1XX, and PD-1 DNR licensed from Memorial Sloan Kettering to improve efficacy, persistence, and durability of response, and to tackle both hematologic and solid tumors. We believe we are strongly positioned to provide patients with meaningful clinical benefit and create significant value. To that end, I am excited to report that our collaborators at MSK have recently submitted an IND application to the FDA for next-generation mesothelin-targeted autologous CAR T immunotherapy ATA2271. We also continue to advance our off-the-shelf allogeneic T-cell immunotherapy manufacturing platform. We are completing the manufacturing process validation activities for tab-cel while building inventory according to our commercial product supply strategy. Our EBV T-cell manufacturing platform continues to evolve and scale up at our wholly-owned facility in Thousand Oaks, California. We have generated data confirming that the use of stirred-tank perfusion bioreactors improves yield. Importantly, these data confirm that ATA188 can be manufactured in such stirred-tank perfusion bioreactors with the potential to produce up to 40,000 doses per one donor leukapheresis. Our scale-up manufacturing technology is a key enabler to deliver biologic-like costs of goods manufactured and will be leveraged across our portfolio, including for allogeneic CAR T programs. Now on to our financial results. We ended the second quarter of 2020 with $347.7 million in cash, cash equivalents, and short-term investments. This is an increase from the prior quarter and reflects aggregate net proceeds of $189.3 million from our recent public offering, including the full exercise of the option to purchase additional shares by the underwriters. Cash used from operating activities was $56.6 million for the second quarter of 2020, as compared to $54.6 million for the same period in 2019. We believe that our cash, cash equivalents, and short-term investments as of June 30, 2020 are sufficient to fund planned operations into 2022. In the second quarter, we also successfully onboarded two well-known scientific leaders in the field of cell and gene therapy. Dr. Jakob Dupont was named Global Head of R&D, and Dr. Maria Grazia Roncarolo was appointed to the Board of Directors. Both have deep and diverse expertise in cell and gene therapies, and I am delighted to welcome them to our team. In summary, I am extremely proud of how Atara's team members are continuing to make excellent progress against our key objectives. As a company, we remain committed to our mission, and I want to personally thank all of our employees, contractors, collaborators, and of course the patients we seek to serve for all they do. I hope that everyone on this call today is staying safe and healthy, and I look forward to sharing our progress with you in the weeks and months ahead. I will now turn the call over to our new Head of Research and Development, Dr. Jakob Dupont, to review further details of our program. Jakob?

Thanks, Pascal, and good afternoon, everyone. I'm excited to be part of the Atara team and to provide an update on our innovative portfolio of programs. As Pascal mentioned, we continue to advance tab-cel in Phase 3 for PTLD, for which we have obtained breakthrough therapy designation in the United States and prime designation in Europe. This quarter, we have made significant progress in working with our existing clinical trial sites to enroll and treat new patients in our pivotal study. We've opened several new sites in Europe, notably in Spain, Austria, and Belgium. As a result of the hard work of the Atara staff with the cooperation of our partners at our clinical sites, we are on track to conduct the interim analysis of our Phase 3 trial in PTLD in the third quarter of this year. Following the interim analysis, we intend to meet with the FDA at a pre-BLA meeting in the fourth quarter of this year to discuss the totality of the data, and if the FDA is supportive, we plan to initiate the BLA by the end of this year. As a reminder, in Europe, we are in active discussions with the Pediatric Committee of the European Medicines Agency regarding a Pediatric Investigational Plan or PIP. Following discussions with the prime team and after EMA approval of the PIP, we plan to submit an EU market authorization application for patients with EBV positive PTLD in 2021. Looking ahead, we're on track to initiate enrollment in the Phase 3 multi-cohort study in the second half of this year and are eager to study tab-cel in these patient populations with such high unmet need. We're exploring six populations in the multi-cohort study with a focus on extending further into immunodeficiency associated lymphoproliferative diseases, otherwise known as IA-LPD. In particular, this study will evaluate both treatment-naive and previously treated patients in four patient populations with IA-LPDs, including two cohorts addressing frontline EBV positive PTLD patients with significant unmet need, and two additional cohorts addressing EBV positive LPDs arising out of primary or acquired immune deficiencies, which represent a few thousand patients with addressable EBV driven diseases in the United States alone. We expect the first cohorts to enroll in approximately two years, with data expected in 2023. In addition, we believe there is potential to file either by cohort or for tumor agnostic designation. As a reminder, previously reported clinical data from other EBV driven diseases at ASH in 2018 and frontline and second-line CNS-PTLD and at ESMO 2018 in leiomyosarcoma suggested that tab-cel may provide clinical benefits for these patients. We've also seen relevant clinical data through our tab-cel expanded access program in AID-LPD and PID-LPD, and we will present these as an e-poster, which has already been accepted to the European Society of Medical Oncology meeting in a few weeks' time in Spain. Our Phase 1b program of tab-cel in combination with pembrolizumab in nasopharyngeal cancer (NPC) successfully achieved its safety endpoints in stable disease in a subset of patients. We will look to present these data at an upcoming appropriate forum. Following a strategic review and prioritization of our tab-cel programs, we decided not to progress with the Phase 2 portion of the study at this time, but instead to generate additional translational data from this NPC study to further inform our strategies for this patient population with an evolving medical need. Turning now to our existing program, ATA188 for multiple sclerosis. As most of us know, multiple sclerosis patients remain underserved with the current treatment options, especially as their disease progresses. Sadly, a continued decline in their disease is expected in progressive MS. The current treatment options offer a modest efficacy benefit at best, delaying progression by a few months and clearly not altering the course of disease. We believe there's tremendous opportunity to develop a transformative therapy to help patients in need. We have seen early, but encouraging data with ATA188. Recall, we presented important Phase 1a data for ATA188 at the EAN conference in May, where seven patients showed sustained disability improvement, and 3 out of 6 patients showed sustained disability improvement (SDI) at 6 months that was confirmed at 12 months with our cohort 3 dose. We are now retreating patients in the Phase 1a using the cohort 3 dose in the open-label extension of the study, and we expect to present preliminary open-label extension (OLE) data at an appropriate forum in the second half of this year. In addition, we also expect to present 12-month clinical results for cohort 4 in our Phase 1a study in an appropriate forum in the second half of this year. In June, we enrolled our first patient in our double-blind randomized placebo-controlled study using the cohort 3 dose. This study is designed to evaluate the efficacy and safety of ATA188 in patients with progressive forms of multiple sclerosis. This is certainly an exciting time for this very innovative program and we look forward to continuing to share our clinical results in the future. We're also planning to discuss with the FDA the full dataset from our Phase 1a study to explore possible accelerated regulatory pathways. Moving on to our CAR T portfolio. As Pascal mentioned, we continue to make significant progress on all fronts, even in the midst of COVID-19. We are pleased to announce that our collaborators at Memorial Sloan Kettering have recently submitted an IND application to the USFDA for our next-generation mesothelin-targeted autologous CAR T immunotherapy that we call ATA2271. This marks a significant milestone in the evolution of the program, and we look forward to initiating a Phase 1 study in solid tumors with our collaborators in the very near future. As a reminder, ATA2271 is designed to improve efficacy, persistence, and durability of response using a novel 1XX CAR co-stimulatory domain and cell intrinsic checkpoint inhibition technology with a PD-1 dominant negative receptor. The 1XX technology was innovated by Dr. Michel Sadelain, and the ATA2271 program and PD-1 DNR technologies are led by Dr. Prasad Adusumilli at MSK. Data from IND-enabling studies of ATA2271 were presented at AACR in June of this year. This is the first application of the combination of 1XX CAR co-stimulatory domain and cell intrinsic checkpoint inhibition technology with PD-1 DNR. This construct is associated with less cell exhaustion, improvements in functional persistence, serial cell killing, and in vivo efficacy, which has maintained through multiple tumor rechallenges compared to first-generation CD28/CD3z-based mesothelin CAR. At Atara, we are also making progress through IND-enabling studies with our allogeneic mesothelin CAR T program, which we call ATA3271. This program also utilizes the same 1XX and PD-1 DNR technologies leveraged by our differentiated EBV T cell platform. We are also executing on preclinical IND-enabling studies of our off-the-shelf allogeneic CD19 targeted CAR T, which we call ATA3219. This program utilizes our next-generation CAR T technologies and EBV T cell platform. The ATA3219 is supported by the initial proof of principle from an academic off-the-shelf allogeneic EBV CD19 CAR T clinical study that was presented at the 2020 TCT meeting. These data showed the longest median duration of response in advanced B-cell malignancies for an allogeneic CD19 CAR T of 26.9 months. This data gives us further conviction that our EBV T cell platform has the potential to generate off-the-shelf allogeneic CAR Ts with high response rates, durability, and low risk of toxicity. We've seen that EBV T cells offer numerous advantages as the basis of our allogeneic platform as they are potent cell killers that specifically target disease cells safely, traffic to the sites of disease, expand, and persist in the patient. Most notably, we believe that ATA3219 has the potential to be a best-in-class off-the-shelf allogeneic CD19 CAR T therapy utilizing the next-generation 1XX CAR T co-stimulatory domain and our EBV T cell platform. As I noted, preclinical studies are underway, and we now expect to file an IND in 2021. Finally, I would also like to extend our sincere thanks to our staff, collaborators, patients, and caregivers. We've accomplished much in this quarter, thanks to you. And I look forward to providing updates on our continued progress in the near future. I will now turn the call back to the operator to begin the Q&A portion of the call. Operator?

Okay. Our next question comes from the line of Salim Syed from Mizuho. Your line is now open.

Great. Thanks so much for the color, guys. A few from me on multiple sclerosis, if I can. On ATA188, one, I believe the deadline to submit the late breaking abstract for ACTRIMS is August 13. So Pascal or AJ or Jakob, can you just confirm if you’ve submitted the abstract already, or if not, if you plan on doing it by that deadline? Number two, on the cohort 4 data that we're going to get later this year, I'm curious what your thinking is around moving to a cohort 4 dose for the randomized portion? Like what's your criteria versus cohort 3, if it’s equivalent but marginally better, or do you think you're going to move to that cohort 4 dose or stay at cohort 3? How are you thinking about that? And then just lastly on the OLE, can you just give us a little bit more color about how many patients we can expect to see and from which of the cohorts are those patients coming from? Thank you.

Thank you, Salim. AJ, do you want to answer this?

Sure. Firstly, we are not ready to specify where we plan to present this data. We will confirm that the data will be presented in the second half of this year. Regarding the cohort 4 dose and what our expectations are, could you clarify your question? I apologize if you could repeat that.

Yes, that was basically the question, like what is good and then what's the criteria you have in mind to actually use that as the dose going forward versus sticking with cohort 3.

It's an important question. We definitely prioritize safety, and from what we've observed in earlier cohorts, sustained stability has been a consistent trend. We certainly want to see that continue, but we also need to analyze the entire dataset. We've previously mentioned that having stable disease can be quite significant, along with improvements in sustained disability. Therefore, we'll consider all these elements when deciding whether to incorporate the cohort 4 dose into the study. Our adaptive design allows us to make such decisions promptly, which means it won't hinder the study's progress. Regarding the open-label extension data, we can't specify an exact number at this time. However, it's worth noting that when we selected the cohort 3 dose as the appropriate one to advance, we also opened opportunities for all patients in prior cohorts to transition into the open-label extension. Many patients from cohort 3, who were actively involved in the study, quickly moved over, but we are seeing patients from all four cohorts entering the extension; we just can't currently comment on which cohorts will be represented when we share the data later this year.

Okay. But the cohort 3 patients were the ones that transitioned first, so it's possible we could obtain 15 months of data for cohort 3.

You'll definitely have some patients from cohort 3 in that population.

One other point to mention is that we did enroll patients into the cohort 3 dose for the open-label extension. Therefore, even if some patients were in earlier cohorts at lower doses, they are now receiving treatment in the open-label extension at the cohort 3 dose, as I noted in my presentation.

Understood. I appreciate it.

And also studying throughout that at the time we present the cohort 4 12 months data, we should be able to clarify whether we believe that these data justified the need to add these doses to the CP or not. So be ready for that at the time.

Got it. Thanks Pascal. Appreciate the color, guys. Thank you.

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

Hey, thank you so much. I appreciate you taking the questions. I guess just a question on tab-cel and PTLD. I guess, since your last update at ASH last year, have you enrolled any new patients into that EAP and when will we next see an update from that study?

Thank you, Ben. Jakob, do you want to take that question?

Yes, certainly. So we are obviously focused on the pivotal study, the 302 study, and to continue to get that enrollment. And as you heard, we've achieved the sample size, which now allows us to initiate the interim analysis, which is great. And we do continue to see interest in the EAP and the SPU programs as well. Obviously, we would prefer to divert patients to the pivotal study so that we can achieve as much enrollment as possible. But as Pascal mentioned, these are quite sick patients where there can be times when the EAP or the SPU is a better solution for those patients in urgent need.

And clearly, the next time you can expect an update on tab-cel is in September at ESMO, where, as Jakob has said, we have an e-poster accepted that is going to present data with tab-cel from the EAP in these new patient populations, very exciting new patient population of PID and AID.

Got it. Okay. That's very helpful. And maybe just a follow-up question, maybe also for Dr. Dupont. One thing we've heard about is discussions around the logistics of running a second line PTLD study, and some of the challenges associated with enrolling such prophylactic progressive disease. I guess, turning and thinking about the multi-cohort IA-LPD study, how does this compare to second line PTLD in terms of disease severity and time sensitivity for treatment compared to frontline PTLD and some of these other EBV positive disorders?

Yes. I can start and then have AJ provide more details about the multi-cohort study. We are working with six distinct patient populations in this trial. Each population has its own disease progression pace. For instance, we are focusing on AIDS-associated lymphoproliferative disorder, pediatric immunodeficiency, and other primary conditions. We are targeting sites that operate specialized clinics for these groups. Additionally, we see these conditions as more prevalent than we previously noted, which could allow us to add several thousand patients to our tab-cel opportunity. There are also other indications among the six populations, like leiomyosarcoma, which may grow at a slower rate. While each tumor is unique, some cases of leiomyosarcoma are less urgent regarding treatment. Each of these six populations has specific characteristics, but they all show a significant unmet need, with some progressing quickly. For example, CNS-PTLD is quite critical. AJ, would you like to add anything?

Yes, I have two additional points related to Jakob's comment. There is a significant unmet medical need, especially in the AID PID setting, where the refractory population shows a similarly aggressive progression as seen with PTLD. This is an area where we want to enter as quickly as possible. Additionally, in terms of CNS-PTLD, whether in the first line or refractory setting, patients in this group also tend to experience rapid progression because first line therapies do not effectively penetrate the CNS. This presents a potential opportunity for tab-cel. Even in the first line setting for CNS-PTLD, there is a rapid progression, although not as quick as in relapsed/refractory cases, but it still demonstrates a significant rate of progression.

Okay. Okay. That's all very helpful. Thanks very much.

Thank you. Our next question comes from the line of Marc Frahm from Cowen & Company. Your line is now open.

Hi. Thank you for taking my questions. To start, could you review your plans for the disclosure strategy regarding the interim analysis and the BLA meeting? Specifically, will you inform investors when the interim analysis has been conducted and when the BLA meeting is scheduled?

Yes, Jakob, do you like to start and then I will add anything that needs more detail?

Yes, thanks for the question. We have reached the enrollment necessary to activate the interim analysis, which is positive news. As we mentioned, this analysis is coming up soon, specifically in Q3 of this year, after we have conducted the appropriate follow-up with these patients, so it's imminent. We also plan to request a pre-BLA meeting to discuss the comprehensive data we have. This will include not only the data from the 302 pivotal study, but also our efforts with the legacy tab-cel programs from Memorial Sloan Kettering's Phase 2 studies, including the EAP and SPU programs. We aim to consolidate this extensive clinical data and present it to the FDA after the interim analysis in Q3. Ultimately, this process will lead to a BLA submission before the year's end, contingent upon a favorable outcome from our meeting with the FDA. I’ll now turn it over to Pascal to address the disclosure aspect. We want to avoid disclosing too early to maintain the integrity of the ongoing study. Pascal, if you could provide additional context on the disclosures throughout this process.

Yes. I think there are two aspects in terms of disclosure. In terms of the data themselves, we will seek guidance from the FDA during that pre-BLA meeting on the appropriate time to share such information, to ensure the integrity of the ongoing trial. So that's once we align with them, we can then clarify where we're going to communicate in terms of the appropriate congress, for example. Now disclosure will be also led by the importance of material events there. We believe that the BLA submission is clearly a material event at which we plan to communicate, and hopefully with this alignment with the FDA, we could not only communicate that we've initiated the BLA, but hopefully some top-line data. But again, that would be based on adding an alignment with the FDA, because we want to make sure that we preserve the integrity of the ongoing trial.

Okay. And then maybe to follow-up on the earlier discussion of the multi-cohort trial. You gave the guidance that you think kind of across these cohorts, it may be a few thousand patients that you could potentially ultimately add to the label. Can you give us at least a qualitative level kind of the rough breakdown between the cohorts, or is one or two of those really the primary driver of that couple thousand patients and the ones that we should be most focused on in terms of the market opportunity?

Yes, I think that's a great question. Clearly, the two cohorts with PID and AID have the most patients. We have Slide 27 on the new deck that we just posted that gives you an idea of the population of patients there. There are about 170,000 patients with autoimmune disease and HIV, 35,000 with primary immune deficiency in the U.S. So it’s about 205,000 patient population that risk in the U.S. The disease incidence is low single-digit for AID-LPD and high single digits for PID-LPD. And EBV positive rate is about 30% to 50% in AID-LPD and 30% to 75% in PID-LPD. So all together, it leads to a few thousand first-line and second-line patients only in these two cohorts. Then the other cohort of interest is of course, the first line EBV positive PTLD that are patients where the current therapies are inappropriate, and then CNS for first line and second line. And then it will be much rarer disease, like EBV positive sarcoma including LMS and CAEBV. So that's kind of all the importance of the potential number of patients. And the first two are really the ones that have most patients. That's why this is also a priority in terms of enrollment speed once we initiate that study.

Okay, great. Thank you very much.

And by the way, not only are we going to present data on these two particular cohorts in September at ESMO, but the reason that we are focusing on these is really that the disease itself is very similar to what we see in PTLD. So it's a very nice possible label expansion from our point of view to address a real important medical need in a population of a few thousand patients in a disease that is very similar to the one for which we have a large set of data already in PTLD. So that's also very positive for us to really focus our allocation of resources into this particular Phase 2 multi-cohort study, specifically in this cohort with the high number of patients in a real medical need.

Thank you. Our next question comes from the line of John Newman from Canaccord. Your line is now open.

This is John. Sorry, guys. Sorry about that. Thanks for taking the question. So the question I had is just, if you could talk a little bit about the longer-term view for tab-cel. I know that we're all very focused on the interim analysis, and that makes sense, it's a material event for the company. But you are starting to run a study where you're looking at other EBV positive malignancies. I just wondered if you could talk a little bit about the longer-term opportunity here, because it's one thing to talk about EBV positive PTLD, but it's interesting to start to think about all these other areas. So I just wondered if you could talk a little bit about that opportunity. Thanks.

Yes, maybe I start and then AJ, you can add anything specific on the way we see that multi-cohort study. But from an opportunity point of view, we think it's a great opportunity due to the commonality of these EBV driven mechanisms of disease in immunocompromised patients due to high unmet medical need. And the body of positive clinical data to date that we have already from EAP and SPUs shows that the therapy seems to be working in these patients. So we have that as a very clear opportunity to develop the potential of tab-cel. These should not take too long because as we say, we believe that by 2023, we should have that available in at least the first cohort that are the most important ones there. Now from a regulatory point of view, maybe AJ want to comment on the possibility that we are either to have a specific cohort as a BLA type of indication or a tumor agnostic later. AJ, do you want to comment on that?

Yes, we expect the larger cohorts, AID and PID, to enroll more quickly than others. When we examine the six different cohorts we have, many of them are associated with immunodeficiency and driven by EBV. From this angle, it’s possible that the data generated from AID PID and additional cohorts could support a tumor-agnostic label. Adding that information from the multi-cohort will enhance what we already know about PTLD. Therefore, there is a strong possibility of achieving that goal, and we will evaluate it as we approach the 2023 timeframe mentioned.

Okay, great. And one additional question, not sure if you've mentioned this earlier on the call, but can you talk about plans going forward in terms of when you might put the EBV CAR T against CD19 into the clinic that uses your 1XX mechanism, just given timing on that as of yet? Thanks.

Yes. So this is Jakob. I can mention that. As we've noted, we are in the midst of the IND-enabling studies currently at Atara, and we have disclosed that we are heading towards an IND filing in 2021. So work is progressing well in that regard.

Thank you. Our next question comes from the line of Yigal Nochomovitz from Citi. Your line is now open.

Hi. This is Samantha for Yigal. Thanks very much for taking our question. First from me, I wanted to start with, can you expand more on your decision to focus on the additional EBV positive cancers now versus where back in 2018 when you first generated the data for ASH and as most presentations, what's different now versus then that makes it more attractive to pursue?

Yes. Maybe I can start, and AJ you might want to comment on that. I think clearly at the time, we only presented data from the legacy data at ASH '18 on the CNS-PTLD. Then at ASH 2019, we presented efficacy data on PTLD, but safety data on 61 patients, as you remember that included not only PTLD but other diseases. So we have now this efficacy data on EAP, and this efficacy data is extremely encouraging. And that's one of the reasons we have accelerated our plan. We’ve moved ahead, and we are going to initiate that study very soon. It's really based on data because it's very rare to be able to go directly into a Phase 2 in the way we are planning to do so. And again, there is a slide that explains the protocol on our new investor deck based on already existing clinical data that clearly shows that there is some efficacy in a few patients and an acceptable safety as presented at ASH 2019. So it's based on data that we want to accelerate. At the same time, we know that there is a significant population out there in need of an innovative therapy like tab-cel. So there is a medical need. We have early data, encouraging data, that's why we are accelerating there to make sure that we can provide a solution for this patient. AJ, anything to add?

Yes. Maybe just one additional point. If you take a look at the data that we presented earlier, that was pretty much on the LMS population and CNS-PTLD population. Notice that we haven't presented data on AID PID, and that's coming in September. So as we developed more and more data on AID PID, as you've already heard, that is the largest opportunity for us. So that's also part of the factor in accelerating this program because that data has supported moving the program forward much more rapidly.

Got it. That's helpful. And then just a follow-up. I guess maybe sort of answered this, but what is more attractive about these EBV IA-LPD versus what you saw in the nasopharyngeal cancer trial? And I guess what factors need to fall into place where you would consider pursuing nasopharyngeal cancer again?

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

Yes, certainly. With the AID and PID LPDs, I believe AJ effectively conveyed the value proposition and the opportunities presented by the new data we've generated. Regarding the NPC study, we successfully achieved our objectives of understanding safety and observing some stable disease at this stage. We aim to produce more translational data in this trial, as it involves co-administering a cell therapy with a checkpoint inhibitor, which is currently a highly active area of scientific research. We need to determine whether it's more effective to administer a checkpoint inhibitor alongside a cell therapy, before it, or after it. There are many intriguing scientific questions to address. Therefore, we find it prudent to collaborate with our engaged partners at Merck to tackle these translational queries and design the appropriate studies moving forward. The multi-cohort study presents a straightforward experiment, as we are addressing EBV-driven tumors with these therapies and have strong clinical data thus far. We believe this is the key opportunity and priority to concentrate on while working with Merck to understand the nuances of co-administration and the optimal approach. It is also essential to answer these types of questions for the broader field, as we are at the initial stages of clinical experiments combining a checkpoint inhibitor with a cell therapy.

Clearly, we think that we can go faster to address an important medical need with a relatively large population of a few thousand patients in the U.S. with IA-LPD, particularly the AID PID cohort there, and we want to go fast. That's why we are focusing on that.

Got it. Understood. Thanks very much for taking the question.

Thank you.

Thank you. Our next question comes from the line of Matt Phipps from William Blair. Your line is now open.

Hi there. Rob Andrew on for Matt Phipps here. Thanks very much for taking the questions. Apologies if I'm repeating a prior question here, though I switched between calls there this evening. Just maybe on the multi-cohort study, looking forward to some additional data at ESMO. Perhaps given the rarity of some of these diseases, can you talk about the ease or the strategy for identifying the patients? Are they being treated by the same docs that are treating the PTLD population, and does that mean that the enrollment centers for the upcoming study are likely to be the same? And kind of how common is testing for EBV positivity in these populations? Is that standard, or is that something that is not standardized?

Sure. So maybe just as a couple of points, we've talked about the testing. The testing is actually fairly routine. It's not done as aggressively as it is in the transplant population because you literally track that from the moment that the transplant is done. You want to make sure that their EBV viral load isn't going up, but in these populations, when they develop tumors, it's fairly standard to check for EBV. So there's really not much of a concern in terms of the diagnostic there. The second piece you’re asking about is where do these patients show up? And certainly when you're taking a look at the kind of the larger transplant centers, they almost all will have a dedicated group that's looking at these LPDs for AID PID. So not that there's 100% overlap, but there's significant overlap at the large centers with the PTLD, as well as the AID PID. There will be some separate centers, but the majority that there's a larger group that do overlap. You also get the other populations, the LMS population, we have the CA EBV population, a few others that show up at those centers. So I would say there's significant overlap. We'll have some unique centers that will also add in, but from an operational perspective, there are advantages to that commonality of occurrence.

Okay, great. That's helpful. Thank you. And then maybe if I can just squeeze in a quick follow-up on the pre-BLA meeting prior to the BLA filing. Just to assume, you’re not really envisaging any difficulties in getting this kind of thing organized with the FDA, just given the focus on COVID and kind of the likelihood of a vaccine data coming in?

Jakob?

So thank you, William for the question. Obviously, COVID-19 is a major concern at this point in the world and as Pascal has alluded to as well. I think the very fortunate position that we're in at Atara with tab-cel is that we have breakthrough designation, so that will really have frequent and excellent engagements with the FDA. Similarly in Europe, we have prime designation, which really allows us to have an excellent dialogue. I do think that the agencies have really prioritized discussions for programs that have breakthrough therapy and prime designations. So we've actually had a very good engagement from the agency even during this period of COVID.

Great. Thanks very much.

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

Hi, guys. Thanks so much for taking my question. Just a few for me. One question on ATA188 regarding the durability and non-responders to therapy. I was wondering if there's any developments or updated thinking about using an HLA restriction switch to rescue non-responders and also perhaps patients who may lose response. And along those lines, is there a mechanism in the current randomized Phase 1 Part 2 trial for this rescue, and what's the FDA's view on allowing that to be employed in the context of a pivotal trial or any trial for that matter?

Sure. Part of the question is about defining a non-responder. For us, in the context of transformational therapy, if we can halt or reverse disease progression, that's a significant achievement. So far, most patients have maintained their disability status, making it difficult to identify true non-responders at this stage. Therefore, I wouldn't expect to provide immediate information on this, as we don't currently have anyone who fits the strict definition of a non-responder. However, there are mechanisms built into the trial, including the open-label extension, that allow for switches for anyone considered a non-responder. Regarding your question about the FDA's stance on this, the idea of a restriction switch has already been incorporated into our Phase 3 tab-cel program. We are very familiar with, and comfortable using, this concept. We are applying it similarly to the 188 program. We need more extended observation to gather sufficient experience on switches since we have not yet encountered a situation where we can definitively say a switch is necessary.

Great. That's helpful. Just a quick follow-up. I'm wondering how we should think about the placebo response rate in the current Phase 1 part two MS trial. We've seen from medical experience how this could escalate in Phase 3. If you could provide a refresher on what the typical super response rates are in the progressive population, that would be helpful.

Sure. If we look at the relevant study, it serves as a good reference since we are using a similar endpoint, although with slightly different time points. In that study, the placebo group saw a 0% sustained disability improvement rate in one instance, and around 9.2% in another. We consider that a solid benchmark for what we might anticipate in our study, which would likely fall between a 0% and 9% placebo rate. A key difference between their study and ours is that they allowed participants to continue any existing medications, with the new treatment added on. In contrast, our study will be strictly placebo controlled. This suggests that our observed placebo rate could be on the lower end of the range observed in their study.

Great. Very helpful. Thank you.

Of course, that compares favorably to what we've seen so far and that's in our Phase 1a experience.

Thank you. Our next question comes from the line of Anupam Rama from J.P. Morgan. Your line is now open.

Hey everyone. This is Tessa on the call this evening for Anupam. Thanks for taking our questions. I have two quick ones. We discussed the ESMO update in the prepared remarks and in some earlier questions. Can you provide more details on how you would define a win at the conference? My second question relates to the decision to discontinue development in NPC. What factors influenced that decision? Was it driven by efficacy at all? Also, could you elaborate on the translational work you plan to conduct? Thank you.

Thank you. I'll start with the second question, and then ask Jakob before we talk about ESMO, I guess it's your question. On the NPC, just want to clarify, we're not discontinuing the development. We're just not moving into the Phase 2 as it wasn’t initially planned because we want to do additional work to clarify what is the best path to develop and create some value there for the patient and for tab-cel there. So we're still working on that. We've collaborators at Merck. Jakob, do you want to comment further on what led to that decision?

Yes, absolutely. So, as Pascal noted, we did actually achieve the goals of the Phase 1 portion of the study; we saw very good safety results and stable disease, and we were able to combine the drugs successfully. But as mentioned, we really wanted to, at this point, in terms of prioritization to focus on the resources of Atara on indications where we could really, we were, we felt that we could create a lot of rapid value. There's another aspect here with the evolving treatment landscape in nasopharyngeal cancer as well. So with the uncertainties of the shift in the landscape, and also wanting to understand this key scientific question of checkpoint inhibitor with cell therapy combination, we really wanted to do more translational work. So that is an effort that we've undertaken, at Atara. Obviously, working with colleagues at Merck as well. So we have a number of patient samples from the clinical trial where we're looking at the phenotypes of the cells, before and after treatment, which is cellular therapy with the combination of the checkpoint inhibitors as well. So we'll be able to do a very nice series of experiments both at Atara and then also with our collaborators at Merck. But it really was not as Pascal noted a decision to discontinue the program. It was just to do more work and figure out how to do the right type of experiment in the future, if we choose to do so.

And in terms of resource allocation, we really need to invest where we can create value as rapidly as possible. And as hopefully, we explain in the call and in answering questions, we believe that opportunity in the multi-cohort study with valuable cohorts, particularly those in immunocompromised patients with lymphoproliferative disorders that are very similar to prepare the info, which we have a very clear path to potential regulatory submission in a fairly rapid way. This is where we believe we should invest right now, while we continue to work with Merck on clarifying a path for NPC. Now, your question is more, I guess, is around what type of data are we going to put on that there? AJ, do you want to answer that one?

Yes. In response to your question about what we consider acceptable for that population, it's helpful to reflect on the non-PTLD data we've shared so far. We observed a 17% response rate in one population and a 20% response rate in another, both of which involved relapsed or refractory cases. These groups are significantly ill and have limited treatment options. The AID PID population we are focusing on will be similar, as it will also involve relapsed or refractory situations. Achieving data comparable to or better than what we've seen would be a significant success, given the aggressive nature of the disease in these patients once they have failed their current therapies. This approach differs from what we will explore in the multi-cohort study since we will be looking at both the relapsed refractory and first-line settings.

Great. Thank you for the clarification and the color guys. Appreciate it.

Thank you.

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

Hi, this is Kevin for Maury tonight. I just wanted to circle back briefly to the tab-cel EBV positive PTLD readout. So a quick question just about, given the sample size is smaller than what you had initially planned, do you think that affects your ability at all to hit the desired response rate? And then a quick follow up or follow up, excuse me, on the meeting the pre-BLA meeting with the FDA. I know you talked about what's going into that data package. Can you talk about briefly, what the FDA's expectations might be in terms of that data?

Jakob?

Yes, thank you, Kevin, for your question. Regarding the sample size, I believe we are on track as the study includes a pre-specified interim analysis, which we are currently conducting. This is part of the study design. We are collecting data in Q3 and also including information from historical studies, such as the Memorial Sloan Kettering Phase 2 studies in PTLD, the expanded access program, and single patient use. This is valuable data that the FDA will definitely be interested in, as it provides insights into the safety and clinical benefits of tab-cel, especially for this high unmet need. We have considerable information to compile, and we are actively working on that at Atara. While I won't discuss the specifics of our data package here, I want to address the likelihood of success directly. It seems to be proceeding according to our plan since the interim analysis was part of the original study design. As for FDA expectations, we have breakthrough therapy designation for this program, established based on previously generated data, showing response rates in PTLD between 50% to 80%, depending on patient demographics and our diverse clinical experiences. We have also publicly targeted a 37% response rate, which includes some durability information. This is a figure we've discussed with the FDA. Overall, things appear to be proceeding well from our viewpoint. The interim analysis is approaching, and we are also progressing on organizing the historical data for discussions with the FDA.

Great. That's helpful. Thank you.

Thank you. This concludes our question-and-answer session for today. Thank you for joining the Atara Biotherapeutics second quarter 2020 financial results conference call. You may now disconnect.