Regulatory Update

Jan 4, 2021

Press Release

Ladies and gentlemen, thank you for standing by, and welcome to the Atara Biotherapeutics Conference Call. At this time, all I'd now like to hand the conference over to your host today, Mr. Eric Heilengren, Vice President, Investor Relations and Finance. Please go ahead, sir. Thank you, operator. Good morning, everyone, and welcome to the Atara Biotherapeutics conference call. On today's call, members from the Atara executive team will provide an update on our tab cel regulatory progress. This morning, we issued a press release providing a regulatory update for tab cel in EBV positive PTLD. This press release is available in the Investor and Media section at attarabio.com. Joining me on today's call are Doctor. Pascal Tuchon, President and Chief Executive Officer Doctor. Jacob DuPont, Executive Vice President and Global Head of Research and Development Doctor. Ajay Joshi, Chief Medical Officer Joe Newell, Chief Operations Officer and Upal Kapikar, Chief Financial Officer. We will begin with prepared comments from Pascal, then open up the call for your questions. We would like to remind listeners that during the call, the company's management will be making forward looking statements. Actual results could differ materially from those stated or implied by our forward looking statements due to risks and uncertainties associated with the company's business. These forward looking statements are qualified in their entirety by the cautionary statements contained in today's press release and the company's SEC filings. These statements are made as of today's date, and the company undertakes no obligation to update these statements. Now I'd like to turn the call over to Pascal. Pascal? Thank you, Eric, and thank you all for joining us this morning. We have made excellent progress during the Q4 to prepare for TAP-ten regulatory submissions and potential approval and launch. The progress is on the heels of the interim analysis data we reported on the Q3 conference call for the tab cel pivotal CO2 study or ALLEO. Recall, this interim analysis, which comprised subject with 6 months duration of response follow-up at the time, achieved a 50% objective response rate by independent oncologic and radiographic review. This objective response rate and the safety profile for tab celin allele are consistent with previously published investigator assessed data from historical non pivotal studies with no new safety signals. In addition, as part of a breakthrough therapy designation for FabCell, we've had constructive and regular dialogue with FDA over the last several months and recall in particular that we reached agreement with FDA in October on several key aspects of the tab cel regulatory package, notably that we can initiate the rolling BLA and that we can complete the BLA submission with data from the ALLETE study currently enrolled patients with at least 6 months of follow-up for durability of response. The pivotal allele study data will be the primary basis for approval, while the FDA confirmed that we can use efficacy and safety data from the historical non pivotal studies as supportive data in the BLA filing. Based on these agreements, we expected to initiate the rolling BLA by the end of 2020 and finalize the BLA submission in Q3 2021 with the clinical module. In line with this expectation, we have been ready to initiate the BLA for tab cel since early December, when we finalized the initial preclinical module for the BLA for which the content has been read with FDA. During our regular dialogue with the FDA, we receive feedback that before the rolling BLA can be initiated, there is a procedural decision that the agency must take regarding how the clinical data from the historical non pivotal studies are submitted in a DNA filing. Specifically, this procedural decision relates to whether we submit clinical data from the historical non pivotal studies as parallel analysis or as pooled analysis with the pivotal allele study data. The FDA determination on how we provide the clinical data analysis from the tab cel historical non pivotal studies will be based on the assessment of the comparability of the drug product made at Memorial Sloan Kettering and used in the historical non pivotal studies and the drug product manufactured by ATAR and used in the allele pivotal study. To assist the FDA in answering this specific question, we provided the agency with a comprehensive data package in August to demonstrate comparability between these drug products and then complemented these with supplemental data in Q4 per their request. Based on our ongoing conversation with FDA, we have the understanding that this procedural decision will be made before the end of 2020 so that we could initiate the BLA by then. Unexpectedly, FDA decision on comparability between the MFKCC and the ATARA manufactured drug product has not yet been made. However, we continue to have constructive and ongoing dialogue with the FDA and expect such a procedural decision soon. We will then promptly initiate the rolling DNA since this decision has no impact on the initial preclinical model, which I noted is completed and ready to be submitted. Of utmost importance is that this pending FDA procedural decision has no impact on the critical path to completion for the BLA, and we are on track to do so in Q3 2021. Recall that this critical path is defined by data from 6 months clinical duration of response on additional patients enrolled following the interim analysis. These data will mature in Q2 2021, will then be annualized per the statistical analysis plan submitted to the FDA and included as part of the final clinical module to complete the BLA submission in Q3 2021. We also expect to present this data in an appropriate congress in the later part of 2021. While this delay wasn't expected, we are ready to initiate the rolling BLA submission after we receive clearance from the FDA. We remain on track to complete the submission in Q3 2021, and we are committed to progressing the regulatory package for tab cel so that we can move closer to delivering this transformative therapy to those patients in need. I'll now turn back the call to the operator to begin the Q and A portion of the call. Operator? Our first question comes from the line of Salim Syed with Mizuho. Your line is now open. Great. Thanks so much for the question guys and happy New Year. Couple for me if I can. Just curious just at the time of this, it seems like something that the FDA could have made a decision on prior. I'm just wondering why now they're bringing this up to you guys. Is there something specific regarding the data or if there's a broader change at the FDA in the gene and cell therapy landscape that they're looking at? And then the second question here, if you do have to run a parallel analysis here in your submission, I know they've agreed that you can submit the data based on the pivotal, but is there any risk here at all of them changing their current stance and saying that you would actually require additional patients in the pivotal? Thank you. Thank you, Salim, and happy New Year to you as well. Jacob, do you want to start to answer the first question? Yes, certainly. And thank you, Saad, for the question. Regarding the topic of timing, So the sorry, Pascal, I lost the question. Can that be repeated, please? Yes. I think the question was about the timing. I think as we said, we are submitting all the package for comparability in August and then we have had several interactions since then. They've asked some additional supplemental data we provided them with. And we were expecting, till I think the last minute, to have this particular decision being made by the FDA. So we see that as many as a timing issue there in terms of the decision. We believe that we provided them a comprehensive package to support their decision on the comparability. And that's really where we are today there. That's why we say we have such a constructive dialogue with the FDA that we expect that decision to be taken hopefully soon. Now on your second question, which was around Posadol linked with other FDA positions regarding Celgene, here we believe that there is a very different situation. It's nothing to do with an assay or some kind of inconsistent data between some historical data and pivotal data in EIA. All this is consistent. It's really that they want to clarify whether this analysis of the data, which they very clearly say, these historical non pivotal studies data will be considered as supportive data whether or not they decide that the 2 drug products are comparable. But they want to decide whether then these data should be submitted as a pooled analysis or a parallel analysis. Now Jacob or HJ, do you want to answer on whether we see any risk to the aspect of the approval knowing that, as we say, the pivotal study, the IU study, the FDA has been very clear that this is the primary study for the approval. And this question on the aspects related to the analysis is in fact just a procedural question that they need to decide upon. Yes. That's correct, Pascal, and maybe A. J. Can comment as well. But we have received very clear feedback that the ALLETE study, the Study 302 will be the primary data source for the BLA and that the approval will be based upon the data from the 302 study. However, as you noted as well, non pivotal data from the historical trials will be reviewed by the FDA. And so we have a very clear agreement based upon that October interaction with the FDA in terms of the number of patients that are already enrolled in the ALLEAL study and we just need 6 months duration of follow-up for responders there and that data cut is coming up here in Q2 of this year. So we feel very confident that we do not need to bring new additional patients into that data package from the ALLEAL study. A. J, anything further to add? No. I think that's covered well. Thank you. Great. Thanks so much guys. Our next question comes from Jonathan Miller with Evercore ISI. Your line is now open. Hey, guys. Happy New Year and thanks for the update on this. My question is on the material submitted to the FDA that would indicate that there's something meaning submitted to the FDA that would indicate that there's something meaningful between those two products? Thank you, Florent, for your question and happy to hear to you as well. We clearly believe that these 2 dollars product has demonstrated comparability. But maybe Joe, you want to give a little bit more color to that about why do we believe that we have demonstrated comparability even though the process were slightly different, but the products we believe are comparable. I'll add to Pascal. We took a very comprehensive approach to our comparability study. For our protocol, we established perspective acceptance criteria that had to be met in order for us to conclude we had achieved comparability. We evaluated 15 product lots from each of the manufacturing process versions. Each of those lots were tested for 9 different product attributes to assess comparability. Once testing was confirmed and results completed, we had passed each of the predefined acceptance criteria and a robust statistical analysis. Together, those two statements conclude that we strongly believe we've got comparable product and strong process capability for the commercial product that we're making for inventory for commercial approval. So from that perspective, John, I think we're in a pretty good position. Does it answer your question, John? Yes. I suppose given that your internal bars have been met, I mean, I suppose my real question is what's the upshot if FDA decides one way or the other? The FDA is not going to come out of the field here and say, actually, we think there is a meaningful difference and that has an impact. I think your answer to Salim's question suggests that you think regardless, you're going to be able to file on time and it's not going to impact the submission process. Is that right? Yes. I think it's really a procedural question at the end of the day, John, here because the FDA confirmed to us that whether they believe themselves or they estimate themselves that this is comparable or this is not comparable will not change the fact that the data from historical non pivotal studies will be considered as supportive data. They were very clear about that. It's just a type of analysis that they want to perform, they want us to perform in the final clinical module that is linked with that decision. So if it is comparable, then you can pool the data together. If it is not comparable, you just use that as separate data. And I have that experience in the past and I've had that experience with other type of products there. So it's not that surprising that they want to clarify that questions before confirming the type of analysis in the clinical module that they want us to file with. Okay. Makes perfect sense. Thanks, Our next question comes from Ben Burnett with Stifel. Your line is now open. Great. Thank you. Happy New Year to you guys as well. You touched on this during Celine's question, but I just wanted to better understand what the spectrum of outcomes are here. And I guess in a scenario where the FDA could potentially conclude that this isn't comparable, I guess you would still use this in the data submission, but if I understood you correctly, you can't pull the data in the analysis. Does that change the hurdle or your ability to prove efficacy here at all? Thank you, Ben, for your question. Happy New Year to you as well. No, it doesn't change the hurdle at all. I mean, again, the pivotal study stands alone in itself as the primary analysis for the efficacy and safety of the product. It's just that there have been so much data and great data that have been presented in the past, both from Memorial and also from the compassionate use as well as the expanded access program that we performed and presented at ASH last year that it makes sense for the FDA to want to have a look to this data as well because they are part of to me, it's very similar to when Novartis got Kymriah approved in its first indication. They had supportive data coming from UPenn, but these data were not pooled into the analysis. They were each data were set was analyzed separately there. We believe ourselves that here in that case, we have demonstrated comparability between the 2 drug products, but it is as usual to the FDA to decide whether they agree with us. But again, whether they agree or don't agree with us on this particular aspect of comparability between the product made manufactured at MSK and the product made at Atara, it doesn't really matter in terms of the analysis of the pivotal study itself. Jacob or Jay, do you want to add anything to that on the analysis of the pivotal study? Yes. Pascal, I think that's are presented in parallel or pooled, we believe that the data package supports the label of tab cel for EBV plus PTLD who've received at least one prior therapy. And so we do believe that however, the agency decides upon this procedural step that we're in a favorable position for the submission and the approval of TAVSA. Okay. That's great. One more point of emphasis. AJ? Yes. I was just going to add one more point, Vincent. Sorry for interrupting there. We've talked a little bit about this notion that the pivotal study stands alone. This isn't just us stating that, right? This was reinforced by FDA at during our ongoing discussions with them. So at our last Type B clinical meeting, they reinforced very specifically that the 302 study standalone period and then that the historical non pivotal data are supportive. So when you think about or when you ask about is there a risk to the filing and a risk to the approval based on this comparability piece, 303 stands alone. And we've talked about already the ORR that is achieved at the interim analysis. Finding. It's really more just how the data will appear long term in the label and other discussions. Okay. That's very helpful. Thank you. Our next question comes from Phil Nadeau with Cowen and Company. Your line is now open. Good morning. Happy New Year and thanks for the update also. Just a couple of procedural questions. Why not just cut the data both ways and leave it up to the FDA during the course of the review to decide whether the products are comparable and how the data should be represented on the label? Is that an option that you could follow should the FDA not make a decision anytime soon? Thank you and happy New Year to you as well, Phil. Jacob, do you want to answer that question? Yes, absolutely. So this is actually that we also propose to the agency, as they deliberate on this procedural issue of comparability. But the agency really wants to provide clear feedback to us in terms of how the data should be presented in the filing. So, while we made that proposal, the agency really wants to see the data in one particular format. So that's what we're waiting for with that procedural decision. Great. And then I guess the second question, if I heard you correctly in the prepared remarks, you noted that this decision doesn't have any impact on how the preclinical data are presented and that module is ready to be submitted. So why not start the BLA submission with that module and then submit the clinical data once this decision is made? Why does the initiation of the BLA have to await this decision if other parts of the or other modules aren't affected? No, thank you for your question there. Jacob? Yes, absolutely. And so, the great news is that module is ready for submission and that's been pre reviewed in discussions with the FDA previously. But from a procedural perspective, the agency really wants to give clear feedback to us and resolution to all issues and procedural aspects before we initiate. So this really is the FDA's preference to resolve this particular issue of the submission of the clinical data filing and we're certainly adhering to that guidance from the agency. Perfect. Thanks for taking my questions. Thank you, Phil. Our next question comes from Maury Raycroft with Jefferies. Your line is now open. Hi, good morning, everyone, and Happy New Year. Thanks for taking my question. So you said you've been in ongoing dialogue with FDA. Just wondering if you could provide more specifics on who you're speaking with at FDA and who you're waiting to hear from? And are you interacting with the same people who you interacted with prior to the start of the Phase IIIs when comparability was a key question or key discussion point back in 2016 2017? 16? Yes. Thank you. So we are interacting with Cboe, of course, there. And we have a clinical reviewer and a CMC reviewer, of course a team, I mean nothing very specific there. And this is a team that has been following the tab cel discussion for some time now. I don't know, Jacob, whether you recall whether back in well, neither Jacob nor myself were there, but I believe that it's been a similar team or same team since the beginning there. Jacob, any or maybe A. J, any comment on that? Yes. A. J, do you want to comment? Yes. As far as I recall, I've been with the company for a bit over 4 years now and this is the same group, at least in terms of a couple of leaders that Pascal mentioned. It's the same group, including on the CMC side that's been with the program for years. Got it. Okay. Thanks for taking my question. And the dialogue has been very constructive, and we are pleased with the way things are moving in terms of the discussion there. And again, the clarity that we had back in September October is really what made us very confident together with the interim analysis showing this 50% objective response rate and no new safety signal. It's really what made us confident that we are moving forward. And we can really expect to complete that submission in Q3 2021 once we have the follow-up that is required for these additional patients. Our next question comes from Anupam Rama with JPMorgan. Your line is now open. Hi, guys. This is Tessa on the call for Anupam this morning. Happy New Year from us. Just one quickly. In your view, what are the advantages to a pooled analysis versus separately kind of presenting a parallel analysis? Maybe you could just walk that through for us. Thanks so much. Yes. No, thank you, Jesper, for your question. And clearly, as we said, we believe that these 2 products, these 2 drug products have demonstrated comparability between the one manufactured by MSK used in this historical study and the one manufactured by Atara used in a pivotal study. And by the way, that will then be used in a commercial phase there. We believe that they have demonstrated comparability and we believe it may be advantageous to have all that are reviewed as a pool analysis to have more extensive data set in the label there. So it's again the studies, the pivotal study standalone, but having additional data, especially in terms of duration of response, as you know, we have had data with 2 years of our overall survival in responders, over 80%. So these are data that have been published or they are out there already, We believe it could be good to have that to have a more extensive data set. Ajay or Jacob, anything to add? Yes. Go ahead, A. J. No. I think, Pascal, I think you covered it well. At the end of the day, it's like many other things. It's really just going to be a question of how the data appear in the label. And to your question of does pooled versus parallel help you? You heard Pascal talk about how Novartis had essentially parallel data, right? So you can have a very successful approval launch, etcetera, with parallel. The pool may give the more data that they let you put together in general, it makes it easier once you're out in the commercial setting potentially. But really these are small things at the end of the day. The key win for us and I just can't reinforce this more is that FDA clearly stated that the historical non pivotal data are supportive, which from our perspective, I mean they're going to make their way into the label. It's just a question of what the overall format looks like. So, we don't believe that there's significant differences here and certainly no impact on approvability or hurdles or bars for approval. Great. That's very helpful. Thanks for taking our questions. Yes. I think we believe we can be successful really with both. We just need the FDA to decide. Our next question comes from the line of Tony Butler with Roth Capital. Pascal, two questions, please. One is, I'm very respectful of the products made by MSK and by Atara. The question is, are any questions actually going back to MSK that they need to address? That's point 1. And number 2 is, both you and I think A. J. Made reference to the Kymriah label. I don't recall, but was that UPenn data actually put in their label even though it was separated from a pooled data set? Thank you. Yes. Thank you. And happy New Year to you as well, Toni. So there is no need for MSK to do anything there in terms of answering questions. We have all the data we need to answer the questions. And this comparability study that Joe was mentioning, very comprehensive, very robust analysis we did, has been done by ATAR. So we have all what we need, and we can answer questions from the FDA based on ATAR data available data there. So that's one important aspect. Now the second aspect of your question, what happened in this particular case of Kymriah and Novartis that the data from UPenn were not part of the label, even though they were used as supportive data. And you may remember they were part of the ODAC and the submission there. So they certainly play a role there, but they were not part of the label. Perfect. Thank you so very much. Our next question comes from Yigal Nochomovitz with Citigroup. Your line is now open. Hi, great. Thank you very much for taking the questions, and happy New Year to everyone. Just one question following up on the prior questions. Is there any advantage for the pooled versus the parallel analysis when it comes to commenting on the statistical power for the study? Or is that really not a relevant consideration? Thank you, Yigal. And I'll leave it to you. No, it's not relevant. Jacob H. J, do you want to give more flavor there? I mean, again, the statistical analysis has been set up for the pivotal study, and we have the right number of patients there and the right duration of follow-up to come. But A. J, Jacob, anything to add? Yes, absolutely. So I think that's absolutely right. So as we've articulated, the ALLEAL study really is the centerpiece of the BLA filing and that's what the statistical analysis is based around. Now the great news is, as we achieved in October of this year was the agreement with the agency that they will review the historical non pivotal data as well, either in a pooled or in a parallel advantage. So that data will contribute to the agency's overall assessment of efficacy and safety for tab cel and EBV positive PTLD. So we think that we will get the benefit of that historical data even if it's in the parallel analysis. But again, the statistical analysis plan really is focused upon the ALLEAL study, the pivotal trial. Got it. Thanks. And then just one procedural question. Could you review how many modules are in the BLA and the cadence of when each of these modules is expected to be submitted to in order to conclude the submission by 3Q 'twenty one as guided? Yes. So we're going to start with the preclinical module and end with the clinical module. And in between, we'll have the CMC modules. But Jacob or Ajay, do you want to give more details there? Yes. So I can give a little detail and Ajay can follow. But as mentioned, we'll start with that module 4, which is a preclinical data. Then the expectation will be in the rolling BLA that we will next submit the module 3, which will be the CMC module. And then the final piece will be the module 5, the clinical data that will be submitted here in Q3 of 2021. Again, importantly, our guidance has not changed that we're still on track to complete the BLA filing for TAVSO here by Q3 and that will be the final piece of the rolling BLA submission based upon this data cut of the ALLEAL data that will occur here in Q2, which will give us then the 6 months follow-up on the additional patients that have already been enrolled on the study. But A. J, anything further to add regarding the BLA? No, Jacob, I think that covers it. Thanks. Yes. So we have a plan to schedule, Ligal, that is very clear. And that's why we are confident about our expectation to complete that BLA in Q3 2021 based on these additional follow-up that we're going to have on these patients that have been enrolled after the IA was done in Q3. Great. Thank you very much, Pascal and team.