Earnings Call Transcript - ALLO Q3 2021

Operator, Operator

Hello, thank you for standing by, and welcome to Allogene Therapeutics Third Quarter 2021 Conference Call. At this time, all participant lines are in a listen-only mode. After the speakers' presentation, there will be a question-and-answer session. Please be aware that today's conference is being recorded. I would now like to hand the conference over to Christine Cassiano, Chief Communications Officer. Ms. Cassiano, you may begin.

Christine Cassiano, Chief Communications Officer

Thank you, operator, and welcome to all who join the call. After the market closed today, Allogene issued a press release that provides a corporate update and financial results for Q3 2021. This press release and today's webcast are both available on our website. Joining me on the call today are Dr. David Chang, President and Chief Executive Officer; Dr. Rafael Amado, Executive Vice President of Research and Development and Chief Medical Officer; and Dr. Eric Schmidt, Chief Financial Officer. During today's call, we will be making certain forward-looking statements. These may include statements regarding the timing and ability to advance our clinical trials and regulatory matters, our clinical data and 2021 financial guidance among other things. These forward-looking statements are based on current information, assumptions, and the expectations that are subject to change. A description of potential risks can be found in our earnings press release and latest SEC disclosure documents. You are cautioned not to place undue reliance on these forward-looking statements and Allogene disclaims any obligation to update these statements. I'll now turn the call over to David.

David Chang, President and CEO

Thank you, Christine, and good afternoon. In October, we communicated that the FDA had placed a clinical hold on our AlloCAR-T clinical programs based on the chromosomal abnormality observed in one patient in the ALPHA2 trial. Although we have been unable to treat patients while the hold is in place, multiple other workstreams at Allogene continue, including preparation for our Phase 2 pivotal trial on ALLO-501A, advancement of our Cell Forge 1 manufacturing facility and all our preclinical work on solid tumor targets and next generation technologies. On today's call, we will share a brief update on the clinical hold and perhaps even more importantly the ultimate reason that we remain committed to advancing our platform, our data, and the potential impact to patients in need. Let me first start with what's at the top of mind. Since we announced the clinical hold on October 7th, we have been actively engaged with the FDA in discussions that we hope will lead to a timely resolution. We are extremely appreciative of the time and attention that the FDA has devoted to this matter, which we believe has implications not only for the field of allogeneic cell therapy, but also the broader field of cell therapy. I'm also grateful to our team at Allogene, which is making great progress in generating information for us and the field to understand and properly address the chromosomal abnormalities observed in our patients. The FDA's stated mission is to ensure the safety and efficacy of medical products, but the agency has also been mandated by Congress to expedite product development. As FDA leadership has shared at recent public forums, they have identified the development of the allogeneic CAR T derived from healthy donor cells as a potential way to increase access to the therapy and decrease manufacturing time and cost. We recognize the FDA's responsibility to ensure patient safety while supporting innovation. The FDA has continued its review of our end of Phase 1 materials submitted in anticipation for a potential ALLO-501A pivotal Phase 2 trial. From Allogene's perspective, we understand our own responsibility that comes with being a pioneer in the field of cell therapy and look forward to doing everything necessary to facilitate a safe and timely resumption of our clinical studies. During our interaction with FDA, we have remained in close contact with our investigators, including the clinician, who is caring for a patient who subsequently received an allogeneic stem cell transplant. We have heard from many of these investigators that they look forward to the reinitiation of our trials and view our AlloCAR T product as an important therapeutic option for patients, particularly for many of their patients who cannot wait for the delivery of autologous CAR T cells or don't want to risk manufacturing failure. Most importantly, we believe in the potential of our AlloCAR T products and have treated now more than 130 patients with lymphoma, multiple myeloma, and renal cell carcinoma across five Phase 1 studies. In the ALPHA1 trial alone, we have treated over 60 lymphoma patients and we are excited to share updated data at the ASH conference in December. I will now turn the call over to Rafael to preview our upcoming data presentations.

Rafael Amado, Executive Vice President of Research and Development and Chief Medical Officer

Thank you. As David has noted, I will focus my comments today on data updates from both our anti-CD19 and BCMA programs, which will be presented at next month's ASH Conference. We believe the data disclosed in the ASH abstract for ALLO-501 and ALLO-501A continue to validate our consolidation strategy. ASH will feature an oral presentation on our Phase 1 ALPHA2 trial with ALLO-501A and a poster presentation on the ALPHA study with ALLO-501. Consistent with the data presented at ASCO earlier this year, the updates in the ASH abstract continue to support a favorable clinical profile for AlloCAR in non-Hodgkin's lymphoma and demonstrate that consolidation dosing is well tolerated with a potential for enhanced efficacy compared to a single dose of cells. We chose the term consolidation to describe our unique approach to re-dosing, which goes beyond simple retreatment. Our proprietary lymphodepletion strategy enables us to provide a second dose of cells without readministration of chemotherapy, allowing cells that persist from an initial dose to remain active while newly administered cells can work to consolidate our response to therapy. While the data are early, we believe this strategy holds advantages over other retreatment paradigms that are being studied. As you may recall, data presented from the ALPHA2 study at ASCO earlier this year included six evaluable large T cell lymphoma patients treated with a single dose of ALLO-501A and ten evaluable large B cell lymphoma patients from the consolidation cohort in this study. As of the ASH abstract data cutoff date in July, 15 patients had received the ALLO-501A in the single dose cohort and nine in the consolidation cohort with 12 patients, or six each evaluable for response at day 28. In the consolidation cohort, both the overall response rate and complete response rate were at 67%, with all three partial responses converting to CRs following consolidation. We look forward to presenting data on additional patients from the consolidation cohort data at ASH, recognizing that a few in this group were not able to receive a second dose following the clinical hold. The safety profile of ALLO-501A continues to be manageable in both the single dose and consolidation cohorts. Events of interest in the single dose cohort were previously reported at the 2021 ASCO Annual Meeting. In the consolidation cohort, there was no cytokine release syndrome, no graft-versus-host disease, no ICANS, no dose-limiting toxicities, no dose reductions, or Grade 3+ infections, and infusion-related reactions were Grade 2. Among all treated patients, cytopenias were the most common adverse event and occurred in 72% of patients. The patient with aplastic anemia and the chromosomal abnormality treated in the ALPHA2 trial was not referenced in the ASH abstract due to the timing of the data cutoff. Meanwhile, we continue to prepare for the advancement of the ALLO-501A program into a pivotal Phase 2 study with the understanding that certain work streams are being delayed by the hold and subject to ongoing discussions with the FDA. In the ASH abstract for the poster presentation of the ALLO-501A ALPHA trial, the updated data continues to highlight that allogeneic CAR T therapy can be effectively and conveniently delivered to patients with relapse refractory non-Hodgkin's lymphoma, with responses observed across all cell doses and tumor histologies. In data presented across 36 CAR T naïve patients, response rates continue to be similar to those seen in autologous CAR T therapy trials, and the modified intent to treat population remains nearly identical to the intent-to-treat population, with 46 or 47 enrolled patients receiving therapy and an average time from enrollment to start therapy of five days. As of the July ASH abstract data cutoff, five additional patients were treated relative to the data previously reported at ASCO earlier this year. Overall, response rates and CR rates remain at 75% and 50% respectively. In the 13 CAR T naïve patients with large B-cell lymphoma, the overall response rate was 62%, and the CR rate was 46%. In the 23 CAR T naïve patients with follicular lymphoma, the overall response rate was 83%, and the CR rate was 52%. Four of the seven follicular lymphoma patients enrolled in the consolidation cohort were evaluable for assessment after consolidation dosing at the time of the data cutoff, with an overall response rate and CR rates of 100% and 75% respectively. As we see ALPHA2, we will report on additional patients treated in the consolidation cohort of ALPHA at the ASH meeting, with a few not able to receive a second dose following the clinical hold. The percent of patients remaining in CR, six months following a single infusion of ALLO-501, was 36% in large B-cell lymphoma, which is similar to six-month CR rates reported in the pivotal trials of autologous CAR T cell therapies, with the longest ongoing CRs at 15 months as of the data cutoff. The six-month CR rates from follicular lymphoma was 28%. There were no cases of GvHD or DLT, as noted previously, one case of Grade 3 ICANS was reported. Grade 1/2 CRS occurred in 22% of patients, with one case of Grade 3 CRS. All were managed with standard protocols. Cytopenias were the most common adverse event and occurred in 83% of patients. Infection rates remained similar to those reported in autologous CAR T trials. There were no new treatment-emerging adverse events reported in this abstract. The oral presentation at ASH from our multiple myeloma program was focused on a single administration of ALLO-715 at higher cell dose cohorts. Subject to the hold, we continue to target 2022 for data from the combination of ALLO-715 with nirogacestat consolidation dosing with ALLO-715 and ALLO-605 through a current study. Findings from the UNIVERSAL abstract indicate that allogeneic CAR T cell therapy can be delivered rapidly and without the need for bridging therapy to patients with refractory multiple myeloma, with a single dose of therapy capable of inducing deep responses. The ASH abstract contains data as of June with 42 patients treated at escalating doses of ALLO-715 and doses of ALLO-647 ranging from 39 milligrams to 90 milligrams. As we see ALPHA trials, the median time from enrollment to lymphodepletion was five days. Patients were in an advanced stage of disease with a median of five prior lines of therapy and 43% of patients were penta refractory. The trial did not permit bridging therapy. When the initial UNIVERSAL data set was presented at ASH 2020, we reported on 26 evaluable patients across all dosing. The efficacy analysis for this ASH presentation, however, will focus on those patients treated at the highest two dose levels of 320 million and 480 million CAR positive cells. At the time of the abstract, 26 patients were treated at the highest two-cell dose levels along with fludarabine, cyclophosphamide and ALLO-647 lymphodepletion. The overall response rate was 62%, with a very good partial response or better rate of 38.5%. Median follow-up for these patients was 7.4 months, with a median duration of response of 8.3 months. Of the 10 patients with a best response of very good partial response or better, eight were found to be MRD negative. No GvHD was observed. The most common Grade 3+ adverse events included cytopenias. CRS was reported in 52% of patients, in all cases Grade 1 and 2, except for one patient with Grade 3. One patient with Grade 2 CRS experienced Grade 1 neurotoxicity that resolved. Grade 3+ infections occurred in 13% of patients, including two previously reported Grade 5 events. We are pleased that the data from UNIVERSAL showed the multiple myeloma patients treated with ALLO-715 can achieve and maintain meaningful response rates. We look forward to providing updated data across our lead product candidate at ASH in December. We remain enthusiastic about our differentiated ALLO CAR T platform and what its potential may mean for patients. I would like now to turn over the call to Eric for an update on our financials.

Eric Schmidt, Chief Financial Officer

Thank you, Rafael, and good afternoon. We ended the quarter in a strong financial position with $861.7 million in cash, cash equivalents and investments. In the third quarter of 2021, our research and development expenses were $58.7 million, which includes $10.1 million of non-cash stock-based compensation expense. General and administrative expenses were $19 million for the third quarter of 2021, which includes $10.8 million in non-cash stock-based compensation expense. Our net loss for the third quarter of 2021 was $78.2 million, or $0.57 per share, including non-cash stock-based compensation expense of $20.9 million. While the clinical hold has detracted from our ability to enroll patients into our five clinical studies, we continue to support multiple research and operational initiatives, including preparation for a potential pivotal Phase 2 study on ALLO-501A and deployment of CGMP production at our Cell Forge 1 manufacturing facility. As a result, we continue to expect our full-year 2021 operational expenses to be between $300 million and $330 million. This includes estimated non-cash stock-based compensation expense of $80 million to $90 million and excludes any impact from development activities. With that, we will now open the call for your questions.

Operator, Operator

Thank you. The first question comes from the line of Tyler Van Buren from Cowen. Your line is now open.

Tyler Van Buren, Analyst

Hey guys, good afternoon. Thanks very much for taking the question. So in the release, you state that there are ongoing discussions with the FDA. I have to ask, is there anything more you could say with respect to these discussions or the nature of them? And if the FDA has formally requested any data on what that might look like, if not, perhaps you could talk about your ongoing internal investigation to generate the data that would make the FDA comfortable, whether that's testing samples from the manufacturing batch that produced the patient sample or other things that you might be doing.

David Chang, President and CEO

Hi Tyler. Good afternoon. This is Dave Chang. Let me take that question. In terms of whether we have received a communication related to the clinical hold, yes, we have received a clinical hold letter that details the FDA's concerns as well as the data requirements. We have met informally with the FDA to discuss some of the details. So, to that extent, we can talk about it, but in terms of the details, other than what we have previously communicated, which is that the agency's concern around a single case of chromosomal abnormality is whether this has any clinical relevance, and also whether there's any evidence of clonal expansion, and also whether there is a relation between the chromosomal abnormalities and gene editing. Our team has made tremendous progress in terms of making a path towards addressing each area of the concern. So, that's about, at this point what we are willing to share. And while the investigations are ongoing and this matter is still under FDA review, we cannot really talk too much into the details.

Tyler Van Buren, Analyst

Thank you.

Operator, Operator

Your next question comes from the line of Michael Yee from Jefferies. Your line is now open.

Unidentified Analyst, Analyst

Hi, this is Dennis on for Mike. Thanks for taking the questions. You outlined a few possible hypotheses on the last call regarding the chromosomal abnormality, whether it's from TALENs or just from T-cell expansion. Has any of those changed given the additional work that you've done? And then number two, can you please lay out some of the timelines over the next few months in terms of your interactions with the FDA? How much back and forth do you expect? Just give the investors a sense of the timelines on when this could be resolved. Thank you.

David Chang, President and CEO

Yes, in terms of FDA interaction, I would say that this is a very active and collaborative interaction. We have had informal discussions as well as ongoing dialogue as we are preparing to respond to the clinical hold letter. So, to that extent, I think this is very positive. With respect to how this may happen. Yes, in the previous conference call, we laid down a couple of different hypotheses, obviously with all the published literature about potential gene editing nucleus to chromosomal structure deletions or abnormalities. We have to take that into a possibility, but we also highlighted that the kind of chromosomal abnormality that we have detected in this patient is also known to happen in healthy T cells as they go onto expansion. So those two possible explanations still serve as the basis of our ongoing investigation.

Operator, Operator

Your next question comes from the line of Michael Schmidt from Guggenheim. Your line is now open.

Michael Schmidt, Analyst

Hey guys, I have two questions. Just another regulatory question. This one is around the end of Phase 1 materials that have been submitted to the FDA. I just wanted to understand, I guess, what needs to be checked off here in order to get the go ahead for the Phase 2 study, which you said, I think is a parallel process alongside the clinical hold investigation.

David Chang, President and CEO

Yes. Mike, Rafael has been leading the end of Phase 1 discussions with the FDA, and I’ll ask him to respond to your question.

Rafael Amado, Executive Vice President of Research and Development and Chief Medical Officer

Yes. I mean obviously our main focus has been on the hold activities and we obviously are fully dedicated to that. And as David said, interacting productively with the FDA. But in spite of that, the FDA has remained engaged with us on the Phase 1, sorry, the Phase 2 study for ALLO-501A. Those discussions have also been very productive. We don’t get into the details of regulatory discussions as this is a matter of policy, but I can tell you that all the discussions, which included not just clinical discussions and the nature of the clinical trial, but also extensive discussions on manufacturing, which has, in this field, are quite important. They have all taken place both for the cell product as well as ALLO-647, which is, as you know, a co-development type of setup. Further than that, I think it would be premature to comment, but we’ve been very busy, I would say with the hold as well as the registration program.

Michael Schmidt, Analyst

Okay, great. And then a question on ALLO-715. I might have missed it, but I’m curious how much additional data you’ll be able to share at ASH on the multiple myeloma study and whether that will or will not include patients that have received the consolidation.

Rafael Amado, Executive Vice President of Research and Development and Chief Medical Officer

In multiple myeloma, we will not include consolidation that started later, and then that will report next year. We will share data with about a few additional patients or some more patients that have been accumulated since the cutoff that was in June, as well as longer follow-up both in terms of responses to our ability and MRD type of data.

Operator, Operator

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

John Newman, Analyst

Hi guys, thanks for taking the question. Also I had a question about the clinical study of the Phase 2 pivotal study for ALLO-501. Just curious generally speaking, if you would say that given the additional data that we’ll be seeing in ASH, you believe that the optimal way forward would be consolidation dosing, and whether that consolidation dosing would apply to both patients with stable disease after the initial dose, as well as a response.

Rafael Amado, Executive Vice President of Research and Development and Chief Medical Officer

Yes. Hi, this is Rafael. And I think what I would say to that is that we are encouraged about the consolidation data. It’s still early for us to say that this is going to be definitive dosing. But as you’ve heard in the prepared remarks, the data is pretty encouraging with conversion from PR to CR. We are as this part of your question doses also patients that have stable disease as well. And so we will look forward to updating data at ASH with additional patients and additional follow-up.

Operator, Operator

The next question comes from the line of Luca Issi from RBC Capital. Your line is now open.

Luca Issi, Analyst

Great. Thanks so much for taking my question. I’ll try to not ask the questions from the clinical hold. So maybe on the pivotal trial, can you just remind us why you believe that the pivotal trial can be single arm? It looks like Genmab has started a pivotal trial for CD3, CD20 bi-specific antibody head to head versus dealer’s choice chemotherapy in a similar setting. So wondering why that’s not the right comp for us to think about it. And then maybe a comment on the competition, obviously we seem to do that from CRISPR a couple of weeks back. I know their data will not be at ASH, but wondering if you have any comments on what your take is on their dataset. Thanks so much.

David Chang, President and CEO

Okay. Luca, thanks for not asking a question about the FDA clinical hold, but your question upon the clinical study design and our approach as we prepare plan the Phase 1 meeting and in preparation of the pivotal Phase 2 study. We don’t want to go too far ahead of the FDA discussion and make sure that we communicate once we finalize the study design. So there are many aspects. I mean, certainly the question around whether we are going to approach it as a single dose or consolidation. I know that it’s an outstanding question and we’re not dodging because we don’t have a position; we have a position. But I think it’s a little bit ahead of the game plus to talk and communicate about the exact study design. Your question around the evolving environment in non-Hodgkin’s lymphoma, the question around single-arm versus in a controlled study, that’s a great one. But I think there are enough precedents in terms of how regulatory agencies, especially the FDA, has reviewed the data. When the data set shows significant improvement over what could be considered as a standard of care. So I think there are many ways that you can sort of review the different regulatory precedents and our position still stands that in terms of the efficacy demonstration of our AlloCAR-T program, we believe that can be done from an uncontrolled single-arm study.

Rafael Amado, Executive Vice President of Research and Development and Chief Medical Officer

And Luca, on CRISPR and the competition, obviously, it’s really not our place to comment on other parties' data. We welcome competition. We think competition makes the field stronger. Certainly, there’s plenty of unmet medical need to support multiple potential entrants in the allogeneic cell therapy space. Obviously, our focus is just on continuing to execute, try and lead this field and optimize our first-in-class products.

Operator, Operator

Your next question comes from the line of Salveen Richter from Goldman Sachs. Your line is now open.

Salveen Richter, Analyst

Good afternoon. Thanks for taking my question. With regard to the investigation, I don’t know if you can comment whether you’ve been able to rule anything out at this point. And then, secondly, on the multiple myeloma data. Are you hitting a plateau here in terms of the dose response, just with regard to dose level four versus dose level three? Any thoughts there would be helpful.

David Chang, President and CEO

Yes, Salveen, this is David. Let me take the first question and I’ll pass the second question to Rafael. Our investigation has been very active and very productive. We know quite a bit, but we want to follow the due process. Our main audience for the investigation is the FDA. Until we complete the response letter and come out of the clinical hold, I think it is premature to detail what has been done and where our position is. From our perspective, the path towards lifting the clinical hold is straightforward. There are some data generation that we have to do, but we see a clear path forward. With regards to multiple myeloma, we will first present on 320 million and 480 million. We don’t have any intention of continuing to dose escalate. Whether we’ve reached a plateau or not, I think is still pretty mature to tell. With more cells, particularly the medium doses of ALLO-647, we see slightly higher responses with 480 million, but the numbers are still very small to be able to tell. So I think the overall answer is that we will probably stop at 480 million and analyze the data and then make a final decision as to what the recommended Phase 2 dose will be.

Operator, Operator

Your next question comes from the line of Jason Gerberry from Bank of America. Your line is open.

Unidentified Analyst, Analyst

This is Parry on the line for Jason. Thanks for taking our question. I guess, just an additional question on the kind of assuming resolution of the clinical holds. Do you anticipate any updates to, I guess, screening protocols for this type of chromosomal abnormalities that could happen? And then a second question, in terms of once you respond to the clinical hold letter to the FDA, how long do you anticipate they’ll be processing that and when you could restart the trials? I guess, just want to better understand when the pivotal trial initiation could start following that response to the FDA.

David Chang, President and CEO

Yes, Parry, let me take the question. I mean, the questions that you are asking are very important. We are working hard to come to a resolution to the issues related to our clinical hold. I mean, some of the questions at this point, we don’t believe that we’re going to have to change what we do in the clinical setting that much. Much of the focus is generating some additional data to include in our clinical response letter. In terms of how long it’s going to take, I mean, I don’t want to speak for the FDA. So let’s just defer that to when that happens. But I’m just going to add that the FDA has been very engaged in this discussion with us.

Operator, Operator

Your next question comes from the line of Cory Kasimov from JPMorgan. Your line is now open.

Cory Kasimov, Analyst

Good afternoon, guys. Thanks for taking the questions. Two for me as well. So first one is with your update today on the ALPHA study, same four to seven patients in the consolidation cohort who are evaluable for response all follicular lymphoma. I’m curious in terms of not having a valuable LBCL patient yet. Is this a function of limited follow-up or baseline disease or something else? And then, second question, there’s obviously some patients who respond very well to a single dose treatment. So are there learnings you can take from the initial data as to why that might be or how to determine what patients get consolidation? Or is this eventually a market where you think everybody goes on to get consolidation with allogeneic therapy? Thank you.

David Chang, President and CEO

Yes. Let me take that question, Cory. So the reason why in our first study the consolidation patients are in follicular lymphoma is that we’ve been preferentially channeling the large cell lymphoma patients towards 501A ALPHA2. So they are—we’ve reported the conversion of PRs to CRs and 67% CR rate. We will update those results at ASH. And then can you repeat the second question please?

Cory Kasimov, Analyst

Yes. In terms of having patients who respond well to single dose treatment, what can you learn from that, why some will be better with single versus the consolidation? Is this a marketplace where you think eventually everyone just goes to get consolidation therapy?

David Chang, President and CEO

Yes, it is true that some patients may do well with a single dose, and we’ve reported extensively that in the ALPHA study and we will provide an update on those patients. We just believe that the second dose can provide an increase in response rate and hopefully durability as we will show more data at ASH. It’s really that delta that we’re looking for in terms of being able to improve beyond what we’re seeing with the autologous therapy. Once we make a decision, every patient will be treated uniformly in the control.

Operator, Operator

Your next question comes from the line of Raju Prasad from William Blair. Your line is now open.

Raju Prasad, Analyst

Thanks for taking the question. I want to get your thoughts on two separate topics. First, kind of piggyback on the last question on consolidation therapy. In the Universal trial—or I’m sorry, on the GSI and TurboCAR therapies, are you thinking about consolidation therapy there or using GSI twice? And then also wanted to get your thoughts on kind of the transform and ZUMA-7 data and how that may pertain to second line transplant-eligible usage when you get to that level for ALLO-501A? Thanks.

David Chang, President and CEO

Yes. The GSI study has a superior time of administration of GSI, so it’s not a single dose. That study is ongoing. We were growing up to the hold and we will resume once we have all this lifted, obviously. We hope to report next year on that experience. The 605 had already started; that’s the TurboCAR. We are making really good progress in that trial. Again, we will report on that study. We continue to put patients following the hold. Essentially, the point with GSI is there’s a finite period during which they will see that after receiving trials. And then your additional question?

Raju Prasad, Analyst

I just wanted to get your thoughts on the transform and ZUMA-7 data and potential for patients in ALLO in second line transplant-eligible patients.

David Chang, President and CEO

Yes. Obviously, the therapies in the autologous setting are moving into earlier lines of therapies. This is not a surprise, and this is obviously great for patients. I think those results were fantastic, and they will have an influence on how we end up developing 501A. We will follow a pathway of starting with relapse refractory patients, but we have plans for full development of the product as time goes on. Clearly, the data from transform has been very encouraging for us to really move 501A as well into earlier lines of therapy when the time is right.

Rafael Amado, Executive Vice President of Research and Development and Chief Medical Officer

Now let me just add that we and others, I mean, certainly after we started talking about consolidation, our peers are also talking about consolidation as an approach, and there is a lot of good rationale including very exciting emerging data. So we are encouraged by it, but the way that we will approach in terms of consolidation in other programs will really have to depend on evidence-based, especially with the turbo CAR. That is a novel technology. What a single infusion of turbo CAR construct will do is our key questions. Stay tuned; great questions, but we will do this step-by-step.

Operator, Operator

Your next question comes from the line of Mark Breidenbach from Oppenheimer. Your line is now open.

Mark Breidenbach, Analyst

Hey, good afternoon. Thanks for taking the question. This is kind of related to one of the previous questions. But I guess I'm wondering before the clinical holds were imposed, if you were able to enroll enough patients in the universal nirogacestat combination cohort and the consolidation dosing cohort and even the IGNITE study to potentially arrive at some sort of answer in 2022 as to which prong of your multi-pronged strategy is working best in myeloma, or if you really think you'll have to enroll additional patients from what you already have in these studies before you'll be able to make any sort of conclusion one way or the other. Thank you.

Rafael Amado, Executive Vice President of Research and Development and Chief Medical Officer

Mark, let me take the question. Obviously, the clinical hold was a headwind for us. We had to stop enrollment in the clinical study, which will definitely impact some of the timelines that we have previously communicated. At this point, we are not ready to really talk about the data flow much of what you're talking about, including the data from the IGNITE, our solid tumor study, the TurboCAR study of ALLO-605, as well as the combination with GSI. They will open for 2022. We will make our best attempt to keep the same timeline, but as expected, the clinical hold is delaying the enrollment. Obviously, we cannot enroll any patients and the data generation timeline.

Operator, Operator

Your next question comes to the line of Reni Benjamin from JMP Securities. Your line is now open.

Reni Benjamin, Analyst

Hey, good afternoon guys. Thanks for taking the questions. David, I know that you mentioned that you didn't want to comment on how long the FDA may take? But could you maybe provide some bookends as to how long it might take for you guys to respond to the FDA? And I guess just maybe one for Eric, is there any impact of the clinical hold on the Overland joint venture, or do you think any of the learnings that you kind of discovered here or learn here can be automatically transferred to the China opportunity?

Rafael Amado, Executive Vice President of Research and Development and Chief Medical Officer

Yes. In terms of the first question, I know that that is central to a lot of people's mind. We will not provide any timeline on the resolution of the clinical hold. But be assured, I mean, the team's working very productively for some additional data generation, and I think we are in pretty good shape to complete the response to the clinical hold. The question around how long does the FDA take before they respond when the company responds to the clinical hold letter? The PDUFA clock for this is 30 days. That is a window during which they would have to respond. They will have to act based on the response that the sponsor provides to the clinical hold letter.

Eric Schmidt, Chief Financial Officer

And Reni, thanks for the question on our Allogene, Overland joint venture in China. Obviously, we'll apply any learnings from our interactions with the FDA and our investigation of the chromosomal abnormality to everything we do going forward. But with regard to specific and direct impact on China and timelines, no, I don't think there is any. That joint venture is proceeding quite well. Obviously, we're still in the phase of building out infrastructure including a manufacturing facility. So we can use the time to continue to lay that groundwork and hopefully be ready to conduct tech transfer in the future at an appropriate time.

Operator, Operator

Your next question comes to the line of Benjamin Burnett from Stifel. Your line is now open.

Unidentified Analyst, Analyst

Yes, good afternoon. This is indiscernible on for Ben. Regarding ALLO-501 and the dosing protocol, can you remind us what conditions require a second dose? Do patients need to meet a minimum response to receive a second dose?

Rafael Amado, Executive Vice President of Research and Development and Chief Medical Officer

Yes, that's correct. So the patient has to have stable disease or better to get the second dose, and they also receive ALLO-647 prior to the second dose if they meet some criteria. If they progress after the first dose, then they don't go on.

Operator, Operator

Your next question comes from the line of Asthika Goonewardene from Truist Securities. Your line is now open.

Asthika Goonewardene, Analyst

Hi guys. Thanks for taking my questions. I'm going to do two as well. Just to follow up on Reni's question: what do you plan on announcing in regard to the ongoing process? I'm wondering, a deal announced when you formally submit a response to the FDA letter or any other particular part of the whole process that's going to happen here? And then maybe an academic question. How do we figure out the right window in which to give the second consolidation dose and maintain adequate pressure on the tumor? We noticed you guys did address that correctly, but LBCL, but maybe the folks that CRISPR waited a little bit too long. So as we think about rolling this out into other tumor types, what's your approach to really figure that out? Thanks.

David Chang, President and CEO

Asthika, let me take the first question on our disclosure strategy. We aren't intending to give a play-by-play account of day-to-day activities at Allogene and interactions with the FDA. I don't honestly think that that suits anyone well, but of course, we're committed to providing updates in a timely fashion when we do have something meaningful and relevant to report. So stay tuned.

Rafael Amado, Executive Vice President of Research and Development and Chief Medical Officer

With respect to the second question, yes, it is a scientific question. For us, one of the key things that we are trying to do with consolidation is to give consolidation without having to give chemotherapy based on lymphodepletion. If we wait too long and for the patient's cells to recover, our belief is that you will need both 647, the anti-CD52 antibody as well as chemotherapy. I don't think we want to go that direction, which is why we are giving the consolidation right now essentially between 28 and 35 days after the first cell infusion is given. I think that really optimizes the cell expansion kinetics as well as our ability to use only 647 for the second cell infusion.

Operator, Operator

Your next question comes to the line of Dane Leone from Raymond James. Your line is now open.

Dane Leone, Analyst

Thank you for taking the questions. Two for me. Firstly, was the chromosomal abnormality found in the starting batch material ahead of infusion into the patient? And then the second question, I'd like to ask is, do you have any updated clarity in discussions around the design of a potential pivotal study for ALLO-501A, whether that study would contain a control arm, or it would be a single arm study? Thank you.

David Chang, President and CEO

Okay. Dane, let me take the first question and I'll ask Rafael to respond to the second one. In terms of when the chromosomal abnormality occurred, that's an important question, but there is a reasonable hypothesis that we believe that it's making, I say that this could be stemming from the gene editing nucleus that we employ for the manufacturing of AlloCAR T cells. But equally possible is that this is more of a natural phenomenon that can occur at some frequency when T-cells undergo expansion. So let me just stop there, without going into the details of how much we know at this point.

Rafael Amado, Executive Vice President of Research and Development and Chief Medical Officer

Yes. Regarding the trial design, as David previously mentioned, these products have all received approval based on single-arm trials, including the latest ones in multiple myeloma. We believe we will follow the same approach, especially since we offer an off-the-shelf therapy with distinct advantages. This includes leukapheresis and the capacity to treat every patient, setting us apart from autologous products. Therefore, we expect that this will be a single-arm trial.

Operator, Operator

Your next question comes from the line of Robert Burns from H.C. Wainwright. Your line is now open.

Unidentified Analyst, Analyst

Hi, this is Mitchell on for Robert. Thank you for taking our questions. The first question is can you comment on any change in development plans after the clinical hold is lifted? Would there be potentially a faster route to approval with the pivotal key setting that you anticipate pursuing?

David Chang, President and CEO

Okay. So in terms of any changes in the clinical study design, obviously, we will not go into those kinds of details. But we do a lot of careful thinking before we finalize clinical design and we stand by in terms of how we are designing studies to safeguard patients, as well as asking many questions that could advance the fields of allogeneic CAR-T therapy.

Unidentified Analyst, Analyst

Okay, great. Thank you. And then for 501A and the data that we could see at the actual ASH presentation, what incremental dataset can we expect there versus what we have in the abstract?

Rafael Amado, Executive Vice President of Research and Development and Chief Medical Officer

Yes, I think it’s hard to speak to that ahead of the Congress. I mean we want to reserve the ability to present it and keep the confidentiality until the timelines of the Congress. So apologies for dodging the question, but stay tuned. You’ll see the answer.

David Chang, President and CEO

And ASH is only four weeks from now.

Operator, Operator

Your next question comes from the line of Kalpit Patel from B. Riley. Your line is now open.

Kalpit Patel, Analyst

Yes, hi, good afternoon. Thanks for taking the question. Maybe a little more color on the planned Phase 2 for ALLO-501A. I guess if you were to implement both single and consolidation dosing into your protocol. Would it just simply be designed as two separate cohorts? I’m just trying to understand if you may need a greater number of total patients or even a larger study and what was required if you were to add that extra cohort. Thanks for the question.

David Chang, President and CEO

Yes. As I said before, we are not going into the details of how we will define the design of the trial. We plan to have a single regimen in this study. So we don’t plan to have a single dose and a consolidation dose; it will be a single regimen in a single arm trial. So that’s as far as we can go with regards to study design.

Operator, Operator

Your last question comes from the line of David Dai from SMBC. Your line is now open.

David Dai, Analyst

Hey guys, thanks for taking the questions. The last question around the ALLO-605 triple CAR-T. Could you share with us some of the type of cytokine armory you’re using to further improve the cell toxic activity of the cells? And also, could you remind us for your clinical trial? Are you using consolidation therapy and also, are you combining with GSK for the ALLO-605?

David Chang, President and CEO

Yes. The study is too many excited about the potential of these CARs to actually expand the degree of exhaustion and have greater anti-tumor activity and potentially perhaps be able to use fewer cells. These are cytokine signaling that are generally damaging cytokines that are atrophic to these cells. We haven’t gone into the details or specifics, but you can imagine those are the kinds of cytokines, how one sees to recover homeostasis after a lymphodepletion. We may decide to use GSI; that is a decision that hasn’t been made yet. In terms of consolidation, I think it’s premature to tell whether or not we’re going to need consolidation or not. We will know it when we have a little bit more data once we resume the trial. Thank you again for joining the call today. We are deeply committed to patient safety. Excuse me. We are deeply committed to patient safety and continuing our work with the FDA to find not only the best resolution today, but the best way to move our field forward tomorrow as we lead the field in the development of allogeneic CAR-T products. Developing novel science into innovative therapies is not easy, but we are confident in our team to bring the first allogeneic CAR-T therapies to patients. We are proud to take the lead, to expand boundaries and to revolutionize the future of cancer immunotherapy.

Operator, Operator

Thank you. Ladies and gentlemen, thank you for your participation in today's conference call. This does conclude the program and you may now log off and disconnect.