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Edited Transcript of ATRA earnings conference call or presentation 8-Aug-19 12:00pm GMT

Q2 2019 Atara Biotherapeutics Inc Earnings Call

SOUTH SAN FRANCISCO Aug 16, 2019 (Thomson StreetEvents) -- Edited Transcript of Atara Biotherapeutics Inc earnings conference call or presentation Thursday, August 8, 2019 at 12:00:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Christopher M. Haqq

Atara Biotherapeutics, Inc. - Executive VP of R&D & Chief Scientific Officer

* John Craighead

Atara Biotherapeutics, Inc. - VP of IR & Corporate Communications

* Manher Joshi

Atara Biotherapeutics, Inc. - Senior VP & Chief Medical Officer

* Pascal Touchon

Atara Biotherapeutics, Inc. - President, CEO & Director

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Conference Call Participants

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* Benjamin Jay Burnett

Stifel, Nicolaus & Company, Incorporated, Research Division - Associate

* Charles Anthony Butler

Roth Capital Partners, LLC, Research Division - MD, Senior Equity Analyst & Head of Biotechnology Research

* Christopher Liu

Canaccord Genuity Corp., Research Division - Research Analyst

* Maryana Ilya Breitman

Goldman Sachs Group Inc., Research Division - Research Analyst

* Matthew Christopher Phipps

William Blair & Company L.L.C., Research Division - Senior Research Analyst

* Philip M. Nadeau

Cowen and Company, LLC, Research Division - MD and Senior Research Analyst

* Salim Qader Syed

Mizuho Securities USA LLC, Research Division - MD, Senior Biotechnology Analyst of Equity Research & Head of Biotechnology Research

* Samantha Lynn Semenkow

Citigroup Inc, Research Division - Senior Associate

* Tessa Thomas Romero

JP Morgan Chase & Co, Research Division - Associate

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Presentation

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Operator [1]

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Good day, ladies and gentlemen, and welcome to the Atara Biotherapeutics Second Quarter 2019 Financial Results Conference Call. (Operator Instructions)

I would now like to turn the conference over to your host, Dr. John Craighead, Vice President, Investor Relations and Corporate Communications. You may begin.

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John Craighead, Atara Biotherapeutics, Inc. - VP of IR & Corporate Communications [2]

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Thank you, operator. Good morning, everyone, and welcome to the Atara Second Quarter 2019 Financial Results and Corporate Update Conference Call. Earlier this morning, we issued a press release providing an overview of the company's second quarter 2019 financial results and recent operational progress. This press release as well as an updated investor presentation, are available in the Investors & Media section of atarabio.com. I'm joined on the call today by Dr. Pascal Touchon, President and Chief Executive Officer; Utpal Koppikar, Chief Financial Officer; Dr. Chris Haqq, Chief Scientific Officer; and Dr. AJ Joshi, Chief Medical Officer. We'll begin with prepared comments from Pascal and then open the call for your questions.

I'd like to remind listeners that 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 the 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 Atara's President and Chief Executive Officer, Pascal Touchon. Pascal?

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Pascal Touchon, Atara Biotherapeutics, Inc. - President, CEO & Director [3]

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Thank you, John, and thank you, everyone, for joining us this morning. Today is my first conference call as the Chief Executive Officer of Atara Biotherapeutics. It has only been a few weeks since I joined Atara in late June, but I have already been impressed by the expertise and commitment of our teams in developing T-cell immunotherapies to transform the lives of patients with serious diseases.

Indeed, I am confident that we are now in a strong position to execute on our commitment and create value for patients, physicians and shareholders across our tab-cel, multiple sclerosis and next-generation CAR T programs. What I will like to do today is, first, provide a brief overview on my background and tell you why I'm so excited about Atara's potential.

I joined from Novartis where I served as Global Head Cell & Gene and member of the Oncology Executive Committee. In this role, my responsibilities included the regulatory approval, pricing and reimbursement and global launch of Kymriah, the first-ever CAR-T approved globally into indications. I was also reading about this global CAR-T strategy, clinical development, manufacturing and technical operations and the financials performance of the oncology cell and gene activities.

Prior to that role, our Global Head Strategy, Business Development and Licensing, Oncology at Novartis, and beforehand, Executive Vice President at Servier, where I initiated the partnership with Selective and Pfizer on allogeneic CAR-T. I believe my experience makes me uniquely suited to carry out Atara's mission to transform the lives of patients with serious diseases.

I think work over the last 5 years in the field of autologous CAR-T as well as first-generation gene-edited allogeneic CAR-T. I believe cell therapy is the next therapeutic frontier in oncology and immunology, following its transformative impact on patients with B-cell malignancies.

What excites me most about Atara is that its T-cell immunotherapy platform could add several important advantages, over both autologous CAR-T therapies and gene-edited allogeneic CAR-T therapies. Indeed, allogeneic T-cell therapies may be immunoprivileged, they're obtained from healthy donors and do not require actual edits, hence, maintaining proliferation and persistence advantages.

As they are matched for each patient from our inventory and available to patients within days, the treatment is more similar to prescribing and administering biologic than the complex process of today's autologous CAR T-cell therapies.

Epstein-Barr Virus, or EBV-specific platform, can lead to therapies directed at EBV-associated diseases like tab-cel and ATA188 as well as allogeneic CAR-T therapies. Our platform is already in clinical development for EBV-associated post-transplant lymphoproliferative disease, or PTLD; and other EBV-associated diseases, including nasopharyngeal carcinoma and multiple sclerosis. We are also developing next-generation CAR-T immunotherapies for both solid tumors and hematological cancer.

Our main priority here is on Mesothelin-targeted next-generation CAR-T candidate with initially ATA2271 an autologous version to rapidly achieve clinical proof-of-concept followed by the allogeneic version. With our unique innovative platform and our own state-of-the-art manufacturing facility, ATOM, we are creating a leadership position in T-cell immunotherapy, developing truly transformative therapies for drug treatment effect, and I feel fortunate to lead such an innovative company.

I will like now to discuss our strategic priorities in greater detail, starting with tab-cel. As recently announced, based on discussions with the FDA, we now plan to initiate first in the U.S., a tab-cel regulatory submission for relapsed refractory EBV+ PTLD during the second half of 2020. We're also in active discussions with the EMA to align on regulatory requirements and determine tab-cel submission timing in Europe.

The FDA has agreed to combine our 2 ongoing tab-cel clinical studies into a single study called ALLELE. Both bone-marrow and solid-organ transplant patients are included, with target enrollment of 33 patients in each cohort. The primary endpoint remains objective response rate. We also plan to conduct an interim analysis prior to initiating BLA submission.

Now let's discuss the digit burden and market characteristics of this aggressive, often deadly, cancer, affecting a limited, but meaningful number of allogeneic stem cell and solid-organ transplant patients.

There are no approved therapies for PTLD. In this disease, this proportionately affects younger patients with a median age of under 40 compared to about 65 for all lymphomas. Unfortunately, the expected survival after failure of the standard first-line therapy of rituximab with or without chemotherapy is between 3 to 12 months in the case of SOT. In HCT, survival after rituximab failure is about 1 month.

In the U.S., we estimate that there are several hundred patients with EBV+ PTLD were failed rituximab with or without chemo. This is a typical material disease with significant unmet medical need. Given the severe disease burden of this condition, we believe tab-cel has the opportunity to deliver a compelling value proposition to patients and health systems.

First off, tab-cel has demonstrated in both Phase II and EAP studies that it has a high and durable treatment effect with objective response rates between 50% and 83%, and overall survival in the responders at 2 years of over 80% in both HCT and SOT.

Secondly, in these studies, we have observed a few treatment-related serious adverse events for tab-cel in PTLD patients with no observed cytokine release syndrome or treatment-related mortality. In addition, tab-cel has a low administration burden with no pretreatment required, a brief IV push administration and only 2 hour post-administration monitoring in clinical trials.

Additionally, all the shared T-cell order, match and supply management system is designed to deliver the treatment within 3 days. Beyond the significant business case in PTLD, we're excited about the potential of tab-cel as an ultra-rare disease pipeline in a product. Tab-cel is an ongoing Phase II clinical development for patients with platinum pretreated metastatic nasopharyngeal carcinoma in combination with pembrolizumab.

This is an EBD-associated cancer with limited overall survival and therapeutic options. Incidence is high in East Asia, but even in the U.S. and Europe, there are hundreds of patients in need of better therapeutic options. Our third tab-cel opportunity is based on the multi-cohort Phase II study that we expect to start in the second half of 2020. We plan to enroll patients having other EBV-related cancers with poor prognosis and for which we have some clinical experience from previous studies.

This study could support potential registrations opportunities. Hence, the same product may progressively treat more and more patients in multiple ultra-rare serious disease.

Turning now to MS program. We're also leveraging here our innovative platform in developing the first EBV-specific T-cell immunotherapy and autoimmune disease. Off-the-shelf allogeneic ATA188 program for multiple sclerosis is ongoing Phase I clinical study for patients with progressive MS.

In late June, we presented the initial safety data for the first 3 dose cohort for ATA188 at the fifth Congress of the European Academy of Neurology. We saw no dose-limiting toxicities and no treatment-related, treatment-emergent adverse event at grade 3 or higher. We are dosing the fourth and final planned cohort now and expect to enroll a total of 24 to 30 patients in the study.

The safety results also add to the overall profile of our allogeneic T-cell platform with favorable tolerability in nonimmunocompromised MS patient as well as immunocompromised PTLD patients. Although designed to evaluate safety and tolerability in order to determine a recommended Phase II dose, the study also includes clinical efficacy secondary endpoint, including a number of established measures of physical, neurological and cognitive functions.

We expect to report initial results on some of its clinical secondary endpoint at ECTRIMS in September as well as additional safety results. On the basis of the Phase Ia data, we plan to proceed into the randomized placebo-controlled portion of the study. In parallel, we plan to initiate a randomized Phase II study of ATA190 and autologous version of ATA188 during the second half of this year to compare the efficacy and safety profile of these 2 EBV-specific cell therapies.

Last, but not least, I would like to provide a brief overview of our next-gen CAR-T portfolio. We had the number of recent presentation at both AACR and ASCO earlier this year. What was most exciting for us were the 2 presentations by your MSK collaborators on Phase I clinical study with Mesothelin-targeted CAR-T immunotherapy in patients with advanced mesothelioma. Mesothelin is highly expressed on cells in aggressive solid tumors, including triple-negative breast cancer, ovarian, pancreatic and nonsmall cell lung cancers as well as mesothelioma.

In the latest ASCO presentation, a subset of 16 patient with malignant mesothelioma, followed for a minimum of 3 months and receiving MSK meso CAR-T, together with anti-PD-1 and meso-depleting chemotherapy show the 12 months overall survival rate of 80% and an objective response rate of 63%. We view these data as highly encouraging and have prioritized on Mesothelin-targeted next-generation CAR-T program, ATA2271. We have a plan in collaboration with MSK to submit an IND for this program in 2020.

Before opening the call to your questions, I would like to comment on our recent public offering. In July, we completed an underwritten public offering of $150 million from the issuance of 6.9 million shares of common stock and 2.9 million presented warrants. These successful offerings strengthen financial positions and funds planned operations into 2021 for key milestone next year, including initiating the tab-cel BLA submission and next-generation Mesothelin CAR-T IND.

I would like now to turn the call back over to the operator, so we can go ahead and take your questions. Operator?

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Questions and Answers

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Operator [1]

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(Operator Instructions) And our first question comes from Anupam Rama from JPMorgan.

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Tessa Thomas Romero, JP Morgan Chase & Co, Research Division - Associate [2]

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This is Tessa filling in for Anupam this morning. So my question is on MS. With first efficacy data for ATA188 coming at ACTRIMS in the coming weeks. Can you walk us through the scope of data here and what the points of differentiation are that we should be looking for in the Phase I readout? Specifically, what are your expectations in the context of the disease for the key secondary endpoints that you will be outlining for us?

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Pascal Touchon, Atara Biotherapeutics, Inc. - President, CEO & Director [3]

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Thank you very much for your question. I will ask AJ Joshi to start answering that question.

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Manher Joshi, Atara Biotherapeutics, Inc. - Senior VP & Chief Medical Officer [4]

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Sure. Thank you, Pascal. So just to put things in perspective, this is, of course, a study that is focusing on the progressive MS population. And really, the focus in progressive MS is to delay deterioration. That's really the end goal. Now in order to assess that particular parameter, most parameters, actually, you need about 1 to 2 years of assessment to really prove anything. So our challenges in setting the study up was how do we get an earlier read than a couple of years. Because as you know, these data are going to be around 6-month data on a couple of cohorts of patients.

We worked with thought leaders to essentially define multiple parameters that are well defined, clinically meaningful and, essentially, assess those parameters across multiple time points. What you're looking for across those parameters is basically similar change across multiple parameters at a specific time point. And what that -- I should step back for just a second. So those parameters assess both clinical function, physical function, cognitive function, it's a variety of MS issues. If you see a similar movement in multiple parameters at a specific time point. That gives you confidence that there's a real signal there at an earlier time point than that 1 to 2 years that I was talking about. So success for us here would look like movement across multiple parameters at the time points that we described when the data was presented.

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Pascal Touchon, Atara Biotherapeutics, Inc. - President, CEO & Director [5]

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And just to add on that, I mean, ACTRIMS is an important step in building up evidence in terms of safety and efficacy for ATA188, so then we can move to -- at a later stage when we have completed this Phase Ia study into Phase Ib. We expect to present initial efficacy results from the lower-dose cohort as well as additional safety results from the higher-dose cohort. The fourth and final plan of growth is almost fully enrolled, but we do not expect to have efficacy data available at the time on the fourth cohort at ACTRIMS in September. And this is just, as I say, a step, and we plan, of course, to progressively present additional data at future congress as they continue to mature.

Other question?

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Tessa Thomas Romero, JP Morgan Chase & Co, Research Division - Associate [6]

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No. that's great. I appreciate the color.

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Operator [7]

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And your next question comes from John Newman from Canaccord Genuity.

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Christopher Liu, Canaccord Genuity Corp., Research Division - Research Analyst [8]

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This is Chris on for John. We're just wondering do you have any incremental color for us for how fast new clinical sites can be opened. And if you have any details -- additional details on what you're doing besides that to help enrollment?

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Pascal Touchon, Atara Biotherapeutics, Inc. - President, CEO & Director [9]

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Thank you for your question. I think AJ, you might want to start answering that question.

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Manher Joshi, Atara Biotherapeutics, Inc. - Senior VP & Chief Medical Officer [10]

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Sure. So in terms of speed of getting sites up and running. For PTLD, you're really looking at larger-scale academic centers. So those -- you typically have a little bit of a longer lead time to open those sites. The reality for us is, though, that we've been building towards this for a while. So much of that lead time has already built in. So we're starting to really see the benefits of getting those sites coming in because as academic centers often takes anywhere between 6 and 9 months to really get up and running.

But again, we've done a lot of that lead-in already. So we do expect to open up several additional sites in the U.S. later this year. In addition, we are opening up additional geographies. Because we just got -- we recently got a no objection letter from Health Canada. So we'll be opening up our first Canadian site later this year and then looking forward to opening up the European site next year.

In terms of any additional work that we're doing, much of the focus for us now is optimizing recruitment at the existing centers. And this has been really -- we've been leveraging a variety of resources, including medical science liaisons and other activities that I implemented in the past -- in previous lives in ultra-rare indications. So multiple activities have been used in ultra-rare indications. So that way -- so I think, again, we've got -- let me step back. Multiple activities from ultra-rare indications that have been used in the past, including MSLs and including a variety of outreaches to both the patient advocacy community as well as the established physician societies.

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Pascal Touchon, Atara Biotherapeutics, Inc. - President, CEO & Director [11]

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And as you say that one of my first priority when I joined was to look in details at the way clinical operations were run to make sure that we optimize our chance to accelerate recruitment in that very important study. I have been satisfied by what I've seen. And that's why I am confident regarding the guidance we've given, which is, of course, linked with the enrollment in these studies.

What we should say as well that some of the challenges that we faced here are linked with the disease itself, it's an ultra-rare disease happily progressing, where sometimes the patient cannot wait for the administrative build-in of being recorded in the study, and that's why we're using our EAP program or SPUs as well to be able to treat these patients.

Additionally, we have to recognize that there have been a number of competitive trials, either directed at PTLD or basket protocol trials in this space that have been started over the last few years, and I think there are about 12 clinical trials right now in that space. So that's also something to take into account into enrollment. But it also tells you a lot about the attractiveness of that particular medical need in terms of new innovative therapies.

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Operator [12]

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And our next question comes from Salim Syed from Mizuho.

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Salim Qader Syed, Mizuho Securities USA LLC, Research Division - MD, Senior Biotechnology Analyst of Equity Research & Head of Biotechnology Research [13]

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A few from me if that's okay. One on the MS program, curious how you guys are thinking about the risk that these T-cells -- they're going to be in MS patients, and they will have immune system. So when you're looking at efficacy, like, how do you guys think about the risk here that you're giving enough T-cells so that they last, right? I know you can compare the PTLD but that was in immune system knockout patients. How do you -- how are you guys thinking about here that these T-cells will be able to last enough to provide the efficacy that you're looking for?

Number two, just on ALLELE program versus auto program, 180 versus 190. If there's any theoretical risk here of one potentially getting pass the blood-brain barrier more than the other? Or if there was a mechanism in place that the human body essentially would reject 188 because it's not perfectly HLA-matched.

And then the last question is just, can you provide more interim details on the tab-cel program, what -- how many patients do you need for the interim? Or what would our hurdle be?

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Pascal Touchon, Atara Biotherapeutics, Inc. - President, CEO & Director [14]

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Thank you very much. AJ, do you want to start?

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Manher Joshi, Atara Biotherapeutics, Inc. - Senior VP & Chief Medical Officer [15]

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Sure. So in terms of the persistence question, we have actually experienced with EBV-directed T-cells -- so EBV targeted T-cells in the immunocompetent population within the nasopharyngeal carcinoma program. So as you know, in the Phase I studies at MSK, we had about 20% response rate in an -- in essentially in immunocompetent population.

So we should be very well able to apply that concept to what's happening in MS because you've got a similar scenario, immunocompetent population using allogeneic T-cells. So from that perspective, I think there's relative confidence that we should have enough persistence to get an efficacy signal and maintain efficacy appropriately. Touchon?

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Pascal Touchon, Atara Biotherapeutics, Inc. - President, CEO & Director [16]

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Chris, do you want to comment on the blood-brain barrier passage?

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Christopher M. Haqq, Atara Biotherapeutics, Inc. - Executive VP of R&D & Chief Scientific Officer [17]

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Sure. I think here is the tab-cel experience is also a good guide in that our experiences was that the EBV-specific T-cells have the ability to traffic. They cross the blood-brain barrier. And in our Phase II experience, we have observed several patients who have had CNS-located PTLD to have objective responses. We expect that to continue as well in the setting of MS. And in previous American Society of Hematology presentations, we've presented on the activity of the antiviral T-cell platform with essentially the same response rate observed in patients with CNS disease compared to those whose disease presented systemically.

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Salim Qader Syed, Mizuho Securities USA LLC, Research Division - MD, Senior Biotechnology Analyst of Equity Research & Head of Biotechnology Research [18]

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And on the auto and ALLELE program in MS, AJ?

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Manher Joshi, Atara Biotherapeutics, Inc. - Senior VP & Chief Medical Officer [19]

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My apologies, would you mind repeating the specific question on autos versus ALLELE?

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Salim Qader Syed, Mizuho Securities USA LLC, Research Division - MD, Senior Biotechnology Analyst of Equity Research & Head of Biotechnology Research [20]

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Oh, no. I think you answered that question. I think the last question was just around the interim details, how many patients and what the -- or the ORR hurdle would be?

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Manher Joshi, Atara Biotherapeutics, Inc. - Senior VP & Chief Medical Officer [21]

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Sure. So as you might imagine, within any time you're doing an interim analysis, and you're working on that with authorities. You're going to have to show substantial benefit and with some adequate level of certainty, which is essentially our ORR. The -- our current ORR when you look at the total patient population can go up 33 patients. The null hypothesis is 20%. So our ORR would have to be 37% to meet the statistical hurdle. And as you might imagine, any interim analysis that we do would have to have a higher ORR statistical hurdle to meet the requirements.

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Operator [22]

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And our next question comes from Matt Phipps from William Blair.

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Matthew Christopher Phipps, William Blair & Company L.L.C., Research Division - Senior Research Analyst [23]

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Pascal, welcome. Good to have you. You guys mentioned in the press release that 34 sites are now enrolling in the pivotal tab-cel trial. So I'm wondering how many of those can enroll both solid-transplant and bone-marrow transplant patients. I suppose it's maybe just one or the other when it was 2 separate studies? There was not -- I mean in all of them -- some of them were overlapping, some of them weren't.

And then also just when can we get some disclosures on the enrollment of the trial? Do we have to wait until you guys say that you've submitted the BLA? Or will we get some info? I mean I think some disclosure on how it's going, would be important, given that how long it's taken.

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Pascal Touchon, Atara Biotherapeutics, Inc. - President, CEO & Director [24]

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Thank you for your questions and for your welcome remark there. So on the number of sites, we say 34 that are unique sites. But of course, some of them are doing both. So we have about 23 sites for field 1 and 27 sites for field 2, that are open for enrollment right now. And I think we -- as we said, we are going to increase these number of sites in the U.S. and also with the recent good news from Canada opened by the end of the year, Canadian site, before moving to Europe, following the CTA submission there.

In terms of the -- your questions on the communication related to the enrollment in such an open study, we have decided not to communicate on the number of patients being on hold. And we will communicate on that at the time of the initiation for submission when we go into that phase of the development of the product there. What is important to have in mind is that we want to recruit the full population in both cohorts, even though we will do the interim analysis on a smaller number of patients.

And just to add on that, I mean, the -- just to be clear, we plan to communicate on our guidance. So when we say we will initiate BLA submission in second half of 2020, we plan to communicate on that initiation at that time.

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Operator [25]

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And our next question comes from Phil Nadeau from Cowen and Company.

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Philip M. Nadeau, Cowen and Company, LLC, Research Division - MD and Senior Research Analyst [26]

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First question is on tab-cel in the European regulatory discussions. Can you give us some sense of what elements still need agreement between the company and the European regulators? Is it endpoints enrollment criteria? And where is the debate?

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Pascal Touchon, Atara Biotherapeutics, Inc. - President, CEO & Director [27]

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I mean as you know, we've adopted a mandate or protocol for SOT, and we have merged 2 studies together, the SOT and HCT study, in 1 study with 2 cohorts. So that's something that has been based on our discussion and constructive dialogue with the FDA, now we need to discuss with the EMA about these changes and see how do they react to that. And then what has that been in terms of the timing of potential submission of the CMA.

We are in a prime process, which is a very unique type of process for advanced therapies, where you cannot regular type of interactions with the rapporteur. And then, of course, you may benefit for an accelerated review then. So we are actively engaged with rapporteur and other members of the committees to be able now to clarify when is the timing for EMA submission of CMA. So it's really around this change in the protocol that is linked with addition of the FDA that now we need to discuss with the EMA.

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Philip M. Nadeau, Cowen and Company, LLC, Research Division - MD and Senior Research Analyst [28]

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And do you have some sense when your discussions with the EMA will conclude?

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Pascal Touchon, Atara Biotherapeutics, Inc. - President, CEO & Director [29]

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It's moving rapidly. I cannot say exactly when it will be concluded. But what I can say that as soon as we have clarity there, we will make that as part of public communication.

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Philip M. Nadeau, Cowen and Company, LLC, Research Division - MD and Senior Research Analyst [30]

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Perfect. And then next question on the next-generation CAR-T. Can you remind us what is the difference between your autologous ATA2271 and the Mesothelin CAR-T that was developed by Memorial Sloan Kettering and -- from which we have data?

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Pascal Touchon, Atara Biotherapeutics, Inc. - President, CEO & Director [31]

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Yes. Chris, do you want to start on that one? Then I will explain our strategy there.

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Christopher M. Haqq, Atara Biotherapeutics, Inc. - Executive VP of R&D & Chief Scientific Officer [32]

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Sure. So we're very excited at the opportunity to incorporate next-generation closed-simulation, 1XX, for example, as well as the T-cell intrinsic checkpoint inhibition through the use of PD-1 dominant negative, and we'll be using the identical binding domain as has been used in the presentations given at AACR and ASCO. So we're using the clinically validated Mesothelin binding domain, together with the best available technologies as we advance the Mesothelin CAR-T program.

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Pascal Touchon, Atara Biotherapeutics, Inc. - President, CEO & Director [33]

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I think the key here is that the binding domain, it's really unique. And in a sense that the data that we have presented -- the early initial data we have presented at ASCO and AACR clearly show a level of safety, first of all and then efficacy that is not very common in Mesothelin-targeted type of therapies.

So we have that the scFv, that's something that we are learning from the first-generation CAR-T development of our collaborators at MSK. And that same as scFv is being part of the construct of the next generation with the new co-stimulatory domain that is aiming at having the right balance between expansion and persistence of the CAR-Ts.

And then, of course, we have added the PD-1 DNR to have really a more physiological way of addressing the need to target PD-1 and make sure PD-1 -- and make sure that we have enough activity of the sales once they are penetrated into the tumor.

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Philip M. Nadeau, Cowen and Company, LLC, Research Division - MD and Senior Research Analyst [34]

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Perfect. And then my last question is on the earlier pipeline, is there any update on ATA3219 and CD19 CAR-T, your ATA2431, C19, CD20, CD22 CAR-T.

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Pascal Touchon, Atara Biotherapeutics, Inc. - President, CEO & Director [35]

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Yes, we are continuing this program, of course, with our collaborators; therefore, the one you mentioned, which is looking at 3 targets there. And then -- so that's with Moffitt, of course.

And then for the CD19, which is a natural development. This development is progressing well. And as you know, objective here is really in a very well-known type of CAR-T targets to be able to show efficacy and safety that will allow to prove the concept of allogeneic CAR-T based on EBV-specific cells.

So both programs are progressing. We don't have any special comment to make on a specific type of achievements there, but they are progressing very well.

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Operator [36]

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And our next question comes from Tony Butler from Roth Capital.

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Charles Anthony Butler, Roth Capital Partners, LLC, Research Division - MD, Senior Equity Analyst & Head of Biotechnology Research [37]

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My question is around 188 in MS and ACTRIMS. There are 3 questions. Number one is, you stated in the release that you're looking at progressive forms of MS, but yet in clinic trials, it's actually both relapse remitting and also progressive. So I'm curious what we get at ECTRIMs directly. That's number one.

Number two is, while you clearly won't have any -- or there will not have been enough time for patients who have been on drug to see probably any changes in MRI. I'm simply trying to understand what could you present that would at least provide enough information that the T-cells do have activity and, more importantly, are affecting the MS directly. I would appreciate some specificity there as possible.

And then finally, did I hear correctly that there were patients or at least a patient that had PTLD MS that did clear. If that's true, could you please describe clinically how that was actually determined?

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Manher Joshi, Atara Biotherapeutics, Inc. - Senior VP & Chief Medical Officer [38]

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Sure. So this is AJ. I -- let me start with the third question. So -- and apologies, if there was any miscommunication or misunderstanding. There's no PTLD patients with MS that we are describing. I think what we were describing earlier is the concept that we have proof that the T-cells do get into the CNS. They are able to cross the blood-brain barrier and access the CNS compartment and exert function because we've had treated patients with PTLD -- CNS PTLD, we've also treated patients in a slightly different setting with CMV retinitis, a variety of other CNS conditions related to CMV with CMV-targeted T-cells. So there's very good proof that these T-cells that we create virally targeted, access the CNS compartment well and exert their function. So that was the true source for why we believe all of these cells are getting in to exert function for MS. So it's not really PTLD. Hope that answers Question 3.

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Charles Anthony Butler, Roth Capital Partners, LLC, Research Division - MD, Senior Equity Analyst & Head of Biotechnology Research [39]

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It does, AJ. My apologies for misunderstanding.

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Manher Joshi, Atara Biotherapeutics, Inc. - Senior VP & Chief Medical Officer [40]

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No, no worries. No worries. Now getting back to first question on progressive versus relapsed remitting. You're right. Our original thought process was to take a look at both as we got deeper and deeper into the understanding of the autologous ATA190 program. And what we wanted to focus in on this program, we specifically decided to stay targeted on progressive MS.

And al as well as it's really a progressive MS population that really doesn't have a lot of inflammatory disease. So when you mentioned MRIs, you're right. There's a lot of times you can get relatively early reads in active disease by tracking MRI status. But this is not active disease. We really want to focus in on the progressive component, which is where really most other therapies have failed to -- have failed, and we think that's the differentiator here.

So for us, the win is the early win. There's an early win and the later win. The later wins are sustained responses on various disability measures like EDSS scores and timed 25-foot walk test and whole-brain volume reduction. But again, those are 1- to 2-year parameters. These are not 6-month parameters.

So the 6-month parameters what you're looking for -- or at least what we're looking for working with our thought leaders is there's about 6 or 7 different measures of physical function, cognitive function, a variety of different things, well-established measures. And what you want to see is stability across those measures or no decline.

Obviously, if you have an improvement, that's fantastic, but it's way too early, quite frankly, to even assess an improvement. But if you're able to show stability and no decline in function, that is the win because these progressive patients will decline in function.

So that's really what we're looking for is can you show stability or no declining function across those various parameters, in -- across multiple parameters in a single patient.

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Pascal Touchon, Atara Biotherapeutics, Inc. - President, CEO & Director [41]

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And again, I mean, this study is really there to determine a Phase II dose that we'll use, by the way, in Phase Ib. And that's mainly based on safety and tolerability. But of course, all these efficacy parameters will inform of choice of the dose for the next portion of the study.

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Charles Anthony Butler, Roth Capital Partners, LLC, Research Division - MD, Senior Equity Analyst & Head of Biotechnology Research [42]

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May I ask one follow-up, and that is in the progressive patients will all have had or will they still be on? And I'm sorry, I did not look for the exclusion criteria. Will they have had or still be on ocrelizumab?

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Manher Joshi, Atara Biotherapeutics, Inc. - Senior VP & Chief Medical Officer [43]

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Yes. They would all need to wash out of ocrelizumab before they enter the study. And ocrelizumab or any other disease-modifying agent would have to be washed out before they enter the study.

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Operator [44]

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And our next question comes from Yigal Nochomovitz from Citi.

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Samantha Lynn Semenkow, Citigroup Inc, Research Division - Senior Associate [45]

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This is Samantha on for Yigal. I wanted to build on an earlier question on your next-gen CAR-T for Mesothelin, specifically in respect to your dominant negative PD-1, can you just go through all the advantages you see with including this into your CAR-T versus just dosing with a PD-1 because the MSK data suggest that you're already getting a really high response rate with pembrolizumab? I'm just curious on your thoughts there.

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Pascal Touchon, Atara Biotherapeutics, Inc. - President, CEO & Director [46]

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No, that's a great question. Thank you. Chris, do you want to start? And then I'll give some feedback as well there.

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Christopher M. Haqq, Atara Biotherapeutics, Inc. - Executive VP of R&D & Chief Scientific Officer [47]

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Sure. So the inclusion of the dominant negative for PD-1. In the preclinical models had additional antitumor efficacy compared to the preclinical combination of CAR T-cells plus an antibody-based checkpoint inhibitor.

Specifically, a higher proportion of the animal studied had complete response of their tumor. And in addition, there was great durability. So we see a couple of important advantages in that way.

In addition, of course, there's a factor of patient convenience as the combination being present in the T-cell itself and able to essentially carry that checkpoint inhibitory function into the tumor in a manner like a Trojan horse, allows them to then have a more convenient treatment potentially as development proceeds.

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Pascal Touchon, Atara Biotherapeutics, Inc. - President, CEO & Director [48]

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Yes. And I think the belief there is that to have the joint push on the construct will really allow a more physical way of targeting PD-1 there. And that is, as Chris has said, back up by some animal data, but of course, we need now to go into patients and to prove that this is a better push than combining with regular administration of PD-1 blocker.

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Samantha Lynn Semenkow, Citigroup Inc, Research Division - Senior Associate [49]

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And then in the MSK data at ASCO, 11 out of those 16 patients were PD-1 negative, but you still saw really great response rates in that population. I'm just curious whether you think expressing PD-L1 is important for this therapy? And do you plan to screen in your potential -- the planned Phase I for in 2020?

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Christopher M. Haqq, Atara Biotherapeutics, Inc. - Executive VP of R&D & Chief Scientific Officer [50]

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So there was no correlation with PD-L1 expression or status on the outcome in the data presented by our MSK collaborators, Dr. Adusumilli and colleagues, at ASCO. One thing to bear in mind is that when T-cells enters the tumor environment, there's a release of cytokines that will dynamically change the expression of PD-L1, and that may be why it's so important to have the combination present. So I think the baseline PD-L1 expression is generally low in mesothelioma, but that may not be the most important factor in a combination therapy that works through an immune mechanism because the cytokines would be expected to dynamically change that access.

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Pascal Touchon, Atara Biotherapeutics, Inc. - President, CEO & Director [51]

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And again, I think the DNR here could be an advantage because then in situ, that's what is really important about the activity of the T-cells. When they have homed to the tumor there, is the in situ immunosuppressive environment that is led by the PDL-1 expression there. And having that for the DNR makes a lot of sense.

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Operator [52]

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And our next question comes from Salveen Richter from Goldman Sachs.

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Maryana Ilya Breitman, Goldman Sachs Group Inc., Research Division - Research Analyst [53]

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Maryana Breitman for Salveen. I have a couple. One of them, following up on the relevance of rationale for the changes. I also wanted to get a better sense for the time line? And I also was trying to understand what are the manufacturing stages that process is in. What other vectors have been made, and how far along are we basically in preparation for the 2020 study?

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Pascal Touchon, Atara Biotherapeutics, Inc. - President, CEO & Director [54]

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Sorry, when you say the change of the time line for the meso...

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Maryana Ilya Breitman, Goldman Sachs Group Inc., Research Division - Research Analyst [55]

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No, no. Just to understand the time line...

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Pascal Touchon, Atara Biotherapeutics, Inc. - President, CEO & Director [56]

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Okay. Okay. Sorry, sorry. No, no. Sorry for that. So we're working with our collaborators at MSK to be able to be ready for the IND. And this is progressing very well. Our guidance has been that we will be -- I mean our collaborators will be filing an IND in 2020 on this next-generation CAR-T, and we are very confident in this guidance.

Meanwhile, as you know, we are also progressing in supporting the first-generation study that is continuing. There is an important medical need. And as you can see the efficacy and safety results are encouraging there. And we believe we are learning a lot from that study that -- and that learnings could be applied to our first study with the next-generation Meso CAR-T there.

So time lines are in line with the guidance, and things are progressing very well there for 2020. And manufacturing at this stage is to be done initially at MSK and will be transferred at our ATOM unit in due time.

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Operator [57]

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And our next question comes from Maury Raycroft from Jefferies.

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Unidentified Analyst, [58]

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This is [David] on for Maury. First question is regarding tab-cel. Just can you share with us any updates on the expanded access program, such as updates on the number of patients included? How about patients enrolling? And if you will report any new data from this program?

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Pascal Touchon, Atara Biotherapeutics, Inc. - President, CEO & Director [59]

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Thank you for your question. So we are not giving any number of patients at this stage. But the program is really recruiting a lot of patients that either cannot participate to the study itself -- to the Phase III study, cannot be enrolled in the Phase III studies or are different type of patients there. So we're very pleased with the enrollment in that program, and we will communicate at future congresses new data on this program.

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Unidentified Analyst, [60]

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Got it. That's very helpful. And the second question is for the tab-cel, can you talk the status of your nasopharyngeal carcinoma trial? How is the enrollment currently going? And what's the sort of plan for the disclosure?

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Pascal Touchon, Atara Biotherapeutics, Inc. - President, CEO & Director [61]

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

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Manher Joshi, Atara Biotherapeutics, Inc. - Senior VP & Chief Medical Officer [62]

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Sure. So the NPC studies, as you know, is ongoing. We're in the first phase of the program where we're looking to enroll anywhere between 12 and 24 patients in the study. As you know, it's the first time we've ever really combined cell therapy with PD-1 inhibition from -- when I say cell therapy, the first time we've combined tab-cel with PD-1 inhibitor. So the major focus for us here is going to be really assessing the safety of the combination initially. From timing of data, we're not expecting to present data this year on that program just yet.

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Unidentified Analyst, [63]

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Got it. That's very helpful. And then last question is on the Mesothelin CAR-T. Can you just share with us any preliminary thoughts around your potential trial design for the CAR-T program in 2020?

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Pascal Touchon, Atara Biotherapeutics, Inc. - President, CEO & Director [64]

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So again, the IND is planned for filing in 2020. We are not right now giving any details on the protocol because we are discussing it right now. And we will give details from that protocol in due time.

Again, that is important that we will take into account all the learnings from the first generation. And what we're doing there. And I think that's an important aspect to optimize the IND and the first-in-human study for these next-generation CAR-T.

We're very confident that we will be able to start that in 2020 as planned. We can appropriate protocol that will really allow us to have proof-of-concept of the clinical efficacy and safety of this next-generation CAR-T as rapidly as possible.

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Operator [65]

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And our last question comes from Ben Burnett from Stifel.

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Benjamin Jay Burnett, Stifel, Nicolaus & Company, Incorporated, Research Division - Associate [66]

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And Pascal, great to see you onboard and congrats. Two questions from me. Just one first. Just to clarify on ATA188. What cohorts or dose levels, specifically, will we see efficacy data for at ACTRIMS?

And then al as well as have patients so far in the Phase I progressed or made it to the point where they can enroll in the open-label extension? And if they have, I guess, what's sort of been the enrollment rate or retention rate into that study?

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Pascal Touchon, Atara Biotherapeutics, Inc. - President, CEO & Director [67]

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Thank you, Ben, for your question. AJ?

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Manher Joshi, Atara Biotherapeutics, Inc. - Senior VP & Chief Medical Officer [68]

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Sure. And I may ask for clarification on part 2 of the question. So in terms of the cohorts, the -- we'll be presenting data on 2 cohorts out to the first 2 cohorts, out to about 6 months' worth of data. We may have a little bit more on one of the initial cohorts. But again, it's really just a timing issue in terms of how long the patients have been in study at this point.

In terms of the enrollment into extension, I apologize. Well, can you clarify that because what we have right now, just as the plan is, as we finish this fourth-dosing cohort, and we're close to finishing the fourth cohort now. We'll make kind of a database decision as to what the dosing will be for the randomized portion of the study. And is that what you're talking about as extension?

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Benjamin Jay Burnett, Stifel, Nicolaus & Company, Incorporated, Research Division - Associate [69]

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Well, I'm referring to a study schema that you guys presented at EAN, where it looks like cohorts 1, 2, 3 and 4 had the opportunity to go into an open-label extension after 1 year of treatment. I just was asking if anyone's made it to that point yet. And what the sort of retention rate's been into that section.

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Manher Joshi, Atara Biotherapeutics, Inc. - Senior VP & Chief Medical Officer [70]

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That's -- okay. No, I apologize. Thank you for the clarity. Yes. So we do have a few patients in -- from the first cohort that have gotten out past a year and are going into the extension. I'm not going to be able to comment on percentages or anything like that because it's a little bit too early, but we do have patients who have gotten out to that time point.

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Benjamin Jay Burnett, Stifel, Nicolaus & Company, Incorporated, Research Division - Associate [71]

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Okay. Understood. And then just one last one on tab-cel and PTLD. I guess can you just talk in a little more detail about the logistics of getting patients enrolled into this study. I guess, really, why has it been so challenging to forecast enrollment rates? And I guess, what gives you the confidence now that enrollment can be accurately forecast going forward?

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Manher Joshi, Atara Biotherapeutics, Inc. - Senior VP & Chief Medical Officer [72]

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Sure. It's a great question. So one of the -- probably the prime -- this is an ultra-rare disease. So clearly, ultra-rare presents challenges. And this is a different challenge than some of the other ultra-rare diseases out there because this is one where the patients really do come up randomly. There's not major centers of excellence, where you're going to have a high concentration of patients. That's step one.

Step two is the timing. Because when you look at this, you're really looking at patients catching them right as they fail therapy. Now normally, that's not that big of a problem. But here, these patients progress so rapidly to that, that there's a short window of opportunity to really help them. So you’re catching them in exactly that window is part -- is a second challenge. We've done really well actually. We've -- in terms of the operational efficiencies we've created to make sure we can catch these patients, that act has gone extremely well, and we've gotten a lot better over the course of the study in achieving that. So that's what gives us a bit more confidence that we'll be able to enroll correctly or at least on the pace that we're targeting.

The third thing just to keep in mind, and I'm going to roll this back into the EAP program a little bit. Part of the challenge that you have, as I mentioned, these patients kind of come up everywhere. And when we find a patient who, for example, is not at a clinical trial site, we'll actually move them over to wherever the clinical trial site is irrespective of where that is in the country.

But you also have to remember that these patients are often so sick that you can't actively transfer them, or they have a medical -- they're not -- they're able to be transferred medically, but they have a specific issue that actually prevents the transfer process. And in those cases, those are patients that get onto our expanded access program, which is what Pascal had alluded to, where we actually have a fair number of patients on our expanded access program, both for PTLD and for other EBV conditions.

But those are the major factors into why I think the enrollment has been a little bit difficult to work through. But since we have focused in on existing centers, we've created these operational efficiencies to make sure that, that timing component, which is really critical, is not as much of a factor as it has been in the past.

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Pascal Touchon, Atara Biotherapeutics, Inc. - President, CEO & Director [73]

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And to build on that, I think our confidence in the guidance is linked to the fact that we've learned so much onto the study that now we are considering that we can deliver what we said regarding the initiation of BLA submission in second half 2020.

Also to take in -- have in mind that in the commercial setting, it will be vastly different there because we'll have the product available within 3 days to any site, any physician that is in need of that product for his patients across the country.

And in the U.S., which is a very attractive market for these type ultra-rare disease, that means that this possibility to treat the patient extremely rapidly offered by our top sellers in allogeneic T-cell that is available within 3 days is going to be immensely useful for patients and physicians.

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Operator [74]

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And I'm not showing any further questions at this time. I will now like to turn the call back to Pascal Touchon, President and CEO, for any further remarks.

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Pascal Touchon, Atara Biotherapeutics, Inc. - President, CEO & Director [75]

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Thank you very much, and thank you, everybody, for having joined that call. I want to thank really you for taking the time to join us today. We look forward to providing update for the remainder of the year on a regular basis as we continue to advance our position as a leader in the off-the-shelf allogeneic T-cell immunotherapy. Thank you very much.

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Operator [76]

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Ladies and gentlemen, thank you for your participation in today's conference. This does conclude today's program. You may all disconnect. Everyone, have a great day.