Allogene Therapeutics Inc (ALLO) 2021 Q3 法說會逐字稿

Hello. Thank you for standing by, and welcome to Allogene Therapeutics' Third Quarter 2021 Conference Call. (Operator Instructions) 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.

Thank you, operator, and welcome to all who joined 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. The 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.

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 a chromosomal abnormality observed in 1 patient in API2 trials. Although we have been unable to treat patients while the hold is in place, multiple other work streams at Allogene continues, including preparation for our Phase II pivotal trial on ALLO-501A, advancement of our cell 41 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 in top of mind.

Since we announced the clinical hold on October 7, 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 are making great progress in generating information for us in 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 allogeneic CAR-T drive from healthy donor cells as potential way to increase access to the therapy and decreased 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 I material submitted in anticipation for a potential ALLO-501A pivotal Phase III 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 the 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, they look forward to reinitiation of our trials and view our allo CAR-T product as an important therapeutic options for patients, calling up how many of their patients cannot wait for the delivery of AlloCAR T cells or don't want to risk manufacturing failure. Most importantly, we believe in the potential of our allo AlloCAR T products and have treated now more than 130 patients with lymphoma, multiple myeloma and renal cell carcinoma across 5 Phase I 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.

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 I ALPHA II trial with ALLO-501A and a poster presentation on an old 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 T in non-Hodgkin's lymphoma and demonstrate that consolidation dosing is well-tolerated with the potential for enhanced efficacy compared to a single dose of cell.

With just the term consolidation to describe our unique approach to redosing, 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 persists from an initial dose to remain active while newly administered sales 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 6 evaluable large T-cell lymphoma patients treated with a single dose of ALLO-501A and 5 evaluable large B-cell lymphoma patients from the consolidation cohort in this study.

And since the ASH abstract data cutoff based in July, 15 patients have received ALLO-501A, fixing the single dose cohort and 9 in the consolidation cohort with 12 patients or 6 each evaluable for response at day 28. In the consolidation cohort, both the overall response rate and complete response rates were at 67% with all 3 partial responses converting to CRs following consolidation. We look forward to presenting data on additional patients in the consolidation cohort 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 Ascania meeting. In the consolidation cohort, there was no cytokine release syndrome, no graft-versus-host disease, no igons, no dose-limiting toxicities, no dose reductions are Grade 3 plus infections and efficient reactions were Grade 2.

Among all treated patients, cytopenias were the most common adverse events that occurred in 72% of patients. The patient with a plastic 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 II study with the understanding that certain work streams are being delayed by the hall and subject to ongoing discussions with the FDA. In the ASH abstract for the poster presentation of the ALLO-501 ALPHA trial, the updated data continues to highlight that allogeneic CAR T therapy can be effectively and conveniently delivered to patients with relapsed/refractory non-Hodgkin's lymphoma with responses observed across all cell doses and tumor histology.

In data presented across 36 CAR-T 9 patients, response rates continue to be similar to those seen in autologous CAR-T therapy trials and the modified intensity population remain nearly identical to the intent to treat population with 46 of 47 enrolled patients receiving therapy and an average time from enrollment to start a therapy of 5 days.

Our softer July ASH abstract data cutoff, 5 additional patients were treated relative to the data previously reported at ASCO earlier this year. Overall response rate and CR rates remain at 75% and 50%, respectively. In the 13 CAR-T naive patients with large B-cell lymphoma, the overall response rate was 62% and the CR rate was 46%. In the 23 CAR-T-naive patients with follicular lymphoma, the overall response rate was 83% and the CR rate was 52%. 4 of the 7 follicular lymphoma patients enrolled in the consolidation cohort were evaluable for assessment after consolidation dosing at the time of the data cut off with an overall response rate and CR rate of 100% and 75%, respectively.

As we also do, we will report on additional patients triggered in the consolidation cohort of ALPHA at the ASH meeting with a few not able to receive a second dose following the clinical home. The percent of patients remaining in CR at 6 months following a single infusion of ALLO-501 was 36% in large cell lymphoma, which is similar to 6-month CR rates reported in the pivotal trials of autologous CAR-T cell therapies with the longest ongoing CR at 15-plus months as of the data cutoff.

The 6-month CR rate from follicular lymphoma was 28%. There were no cases of GVHD or DLTs observed. As noted previously, one case of Grade 3 igons was reported. Grade 1 CRS occur in 22% of patients with 1 case of Grade 3 CRS, all were managed with standard protocol. Cytopenias were the most common adverse events have occurred in 83% of patients. Infection rates remain similar to those observed in autologous CAR T trial. There were no new treatment emerging deaths reported in this abstract. The oral presentation at ASH from our multiple myeloma program will focus on a single administration of ALLO-715 at higher cell dose cohort.

Subject to the whole, we continue to target 2022 for data from the combination of ALLO-715 with neurogasistat, consolidation dosing with ALLO-715 and our ALLO-605 TurboCAR study. Findings from Universal abstract indicate that analogeneic 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 5 days. Patients were in advanced patient disease with a median of 5 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 doses. The efficacy analysis for this ASH presentation, however, will focus on those patients treated at the highest dose levels of $320 million and $480 million CAR positive sales. The time of the abstract, 26 patients were treated at the highest 2 cell dose levels, along with fludarabine, sepofotomide and ALLO-647 for depletion.

The overall response rate was 62% with a very good partial response or better, or VGPR plus rate of 38.5%. Median follow-up for these patients was 7.4 months with a median duration of response or 8.3 months.

Of the 10 patients with the best response of VGPR+, 8 were found to be MRD negative. No GVHD was observed. The most common grade plus adverse events included cytopenias. CRS was reported in 52% of patients. In all cases, Grade 1 and 2, except for 1 patient with Grade 3. One patient with Grade 2 CRS experienced grade 1 neurotoxicity that we saw.

Grade 3 plastic infections occurred in 13% of patients, including 2 previously reported Grade 5 events. We are pleased that the data from Universal showed that 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 candidates at ASH in December.

We remain enthusiastic about our differentiated AlloCAR T platform and what its potential may mean for patients. I'd like now to turn over the call to Eric for an update on our financials.

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 noncash stock-based compensation expense. General and administrative expenses were $19 million for the third quarter of 2021, which includes $10.8 million in noncash stock-based compensation expense.

Our net loss for the third quarter of 2021 was $78.2 million or $0.57 per share, including noncash stock-based compensation expense of $20.9 million. While the clinical hold is detracted from our ability to enroll patients into our 5 clinical studies, we continue to support multiple research and operational initiatives, including preparation for a potential pivotal Phase II study on ALLO-501A and deployment of CGMP production at our CellForge 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 noncash 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 Instructions) The first question comes from the line of Tyler Van Buren from Cowen.

So in the release, you state that there's 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 and what that might look like? If not, perhaps you could talk about your internal -- ongoing internal investigation to generate the data that would make the FDA comfortable, whether that's testing samples from the manufacturing batch that produce the patient sample or other things that you might be doing?

Tyler, this is David Chang. Let me take that question. In terms of whether we have received a communication related to the clinical hold, yes, we have received the clinical hold letter that details FDA's concerns as well as the data requirements.

And also, we have met informally with FDA to discuss some of the details. So to that extent, we can talk about, 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, also whether there is any evidence of coronary expansion and also whether there is a relation between the chromosomal abnormalities and gene editing.

In each of these areas, our team is -- has made a tremendous progress in terms of making a path towards addressing each areas 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 will not really -- we cannot really talk too much into the details.

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

This is Dennis on for Mike. You outlined a few possible hypotheses on the last call regarding the chromosomal abnormality whether it's from Palens 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 time lines over the next few months in terms of your interactions with the FDA? How much back and forth do you expect? And just give investors a sense of the time lines on when this could be resolved?

Yes. In terms of FDA interaction, I would say that this is a very active and collaborative interaction. We have had sort of informal discussion 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 hypothesis, obviously, with -- given all the published literature about the potential of gene editing nuclease to cause chromosomal structural deletions or abnormalities. We have to take that into a possibility.

But we also highlighted that the kind of chromosomal abnomaloty that we have detected in this patient is also known to happen in healthy T cells as they go on the expansion. So those 2 possible explanation still is the basis of our ongoing investigation.

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

I'll ask 2 questions. Just another regulatory question. This one is around the end of Phase I materials that have been submitted to the FDA. And I just wanted to understand, I guess, what needs to be checked off here in order to go -- to get the go ahead for the Phase II study, which you said, I think, is a parallel process side-by-side to the clinical hold investigation?

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

Yes. I mean, obviously, our main focus has been to -- on the old activities. And we obviously are fully dedicated to that. And as David said, we are interacting productively with FDA. But in spite of that, FDA has remained engaged with us on the Phase I -- sorry, the Phase II pivotal trial for 501A. And those discussions have also been very productive. We don't get into the details of regulatory discussions, just as 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, as you know, in this field are quite important.

They all have taken place, both for the cell product as well as 647, which is -- as you know, this is a co-development type sort of development. So further than that, I think it would be premature to comment. But we've been doubly busy, I would say, with the hold as well as the registration program.

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 multimyeloma study? And whether that will or will not include patients that have received the consolidation.

In multiple myeloma, we will not include consolidation that started later and 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 [Caraustar] was in June, as well as longer follow-up both in terms of responses, durability and MRD type of data.

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

I also had a question about the pivotal study, the Phase II pistol study for 501. Just curious, generally speaking, if you would say that given the additional data that we'll be seeing at ASH, do 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?

This is Rafael. 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 a definitive dosing. But as you've heard in the prepared remarks, the data is pretty encouraging with conversion from PR to CR. And we are -- as a part of your question, those is also patients that have stable disease as well. And so we look forward to updating that at ASH us with additional patients and additional follow-up.

Your next question comes from the line of Luca Issi from RBC Capital.

Great. I'll try to not ask questions on 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 PILLAR trial for CD3, CD20 bispecific antibody head-to-head versus dealers choice chemotherapy in a similar setting. So wondering why that's not the right comp for us to think about it? And then maybe on 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 comment on what's your take on their data set.

Okay. Luca, thanks for not asking a question about the FDA clinical hold . But your question on the clinical study design and our approach as we prepare plan the Phase I meeting and in preparation of the pivotal Phase II study. We don't want to go too much 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're going to approach as a single dose or consolidation. I know that is an outstanding question. And we've been sort of starting the question. And it's not -- 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 for us to talk and communicate about exact study design. And your question around given the evolving environment in the non-Hodgkin's lymphoma, the question around the single-arm versus a controlled study, that's a great one.

But I think there are enough precedents in terms of how regulatory agency, especially 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 CAR-T program, we believe that can be done from an uncontrolled single-arm study.

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 feel 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.

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

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 dose response just with regard to dose level 4 versus dose level 3? Any thoughts there would be helpful.

Yes, Salveen, this is David. Let me take the first question, and I'll pass the second question to Rafael. I mean 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 FDA. And until we complete the response letter and come out of the clinical hold, I think it is premature to detail about what has been done and where our position is. I mean from our perspective, the path towards lifting the clinical hold is straightforward. I mean there are some data generation that we have to do, but we see a clear path forward.

Yes. With regards to multiple myeloma, first, we will 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 it's still premature to tell with more sales, particularly at 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 II dose will be.

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

This is Perry on the line for Jason. 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 abnormality that could happen? And then a second question, in terms of once you respond to the clinical, the clinical hold letter to the FDA, how long do you anticipate kind of their processing that and when you could restart the trials? I guess I just want to better understand when the pivotal trial initiation could start following that -- following response to the FDA.

Yes. Perry, let me take the question. I mean the questions that you're asking are very important questions. And we are working hard to come to a resolution to the issues related to our clinical hold. I mean some of the question at this point, we don't believe that we're going to have to change what we do in the clinical setting. And for that matter, I think much of the focus is just generating some additional data to include in our clinical response letter.

So that's what we are doing. And in terms of the second question about 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 by saying that FDA has been very engaged in this discussion with us.

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

So first one is with your update today on the ALPHA study saying 4 of the 7 patients and consolidation cohort about -- who are evaluable for response or all follicular lymphoma. Curious, in terms of not having evaluable LBCL patients 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?

Yes. Let me take that question, Cory. So what -- the reason why in ALPHA study, the consolidation patients are in follicular lymphoma is because we've been preferentially channeling the large cell lymphoma patients towards 501A for ALPHA 2. So there -- we've reported the conversion of CPR to CRs and 67% CR rate. And we will update those results at ASH. And then can you repeat the second question, please?

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

Yes, it is true that some patients may do well with single dose, and we've reported extensively on that on 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 well as we will show more data at ASH. And it's really the delta that we're looking for in terms of being able to improve beyond what we're seeing with the autologous therapy. So once we make a decision, every patient will be treated uniformly in the pivotal trial.

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

I want to get your thoughts on 2 separate topics. First, kind of piggyback on the last question on consolidation therapy. In 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 I also want to get your thoughts on kind of the transform and ZUMA-7 data and how that may pertain to kind of second-line transplant eligible usage when you get to that level for ALLO-501?

Yes. So the DSI study has a period of time of administration of GSI. So it's not a single dose. And that study is ongoing. We are accruing -- we were accruing up to the whole, and we will resume once all this listed, obviously. And then we hope to report next year on that experience. 605 had already started. That's the TurboCAR, and we were making really good progress in that trial.

And again, we will report on that study after we continue to put patients following the whole. So essentially, the point with GSI is there's a finite period of time where they receive it after receiving themselves. And then your additional question?

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

Yes. So I mean, 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 501, we'll follow a pathway of starting with relapsed/refractory patients, but we have planned for full development of the product as time goes on.

And 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 comes.

Let me just add by saying we and others, I mean, certainly, after we started talking about consolidation, our peers are also talking about consolidation as an approach. And there's 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, that really have to depend on evidence-based especially with the TurboCAR, I mean that is a novel technology. I mean what -- a single infusion of turbo construct will do is our key question. So stay tuned, great questions, but we will do this step-by-step matter.

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

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 neuro (inaudible) combination cohort and the consolidation dosing cohort and even the IGNITE study to potentially that some sort of answer in 2022 as to which prong of your multipronged 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.

Mark, let me take that question. Obviously, clinical hold was a headwind for us. I mean, we had to start the enrollment in the clinical study. That will definitely impact some of the time lines 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 the GSI.

They were all planned in -- for 2022. We will make our best attempt to keep the same time line, but as expected. I mean, the clinical hold is delaying the enrollment. Obviously, we cannot enroll any patients and the data generation time line.

Your next question comes from the line of Ren Benjamin from JMP Securities.

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 discover here or learn here can kind of be automatically transferred to the China opportunity?

Yes. In terms of the first question, I know that, that is central to -- in a lot of people's mind. We will not provide any time line on the resolution of the clinical hold. But be assured, I mean, the team is 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 to the -- when company responds to the clinical hold letter.

The PDUFA clock for there is 30 days. I mean, that is a window during which they would have to respond. They will have to act in a baseline response that the sponsor produces provides to the clinical hold letter.

And Ren, 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 time lines, 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.

Your next question comes from the line of Benjamin Burnett from Stifel.

This is Neil Carnahan on for Ben. On ALLO-501 and the protocol around consolidated dosing, can you remind us what triggers the second dose? Do patients need to achieve a minimum response in order to get a second dose?

Yes, that's correct. So the patient has to have stable disease or better to get the second dose. And they also get, as you know, ALLO-605 prior to the second dose if they miss some study criteria. If they progress after the first dose, then they don't go on the second...

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

I want to do 2 as well. Just a follow-up on Ren's question. What will you -- what's your plan on announcing in regarding to the ongoing process? I'm wondering whether you'll announce when you formally submitted a response to the FDA's letter or any other particular part of the whole process that's going to happen here? And then maybe an academic question, how do you 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 with LBCO, but maybe the folks that Cristal waited a little bit too long. So as we think about rolling that into other tumor types, what's your approach to really figure that out?

ASthika, it's Eric. Let me take the first question on our disclosure strategy. We are contending to give a play-by-play 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.

And 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 the consolidation is to give consolidation without having to give chemotherapy based on lymphodepletion. So if we wait too long and when the patient cells do recover, I mean, our belief is that you will need both 647, our 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. And I think that really optimizes the cell expansion kinetics, as well as our ability to use only 647 for the second cell infusion.

Your next question comes from the line of Dane Leone from Raymond James.

Two for me. Firstly, was the clone with 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.

Okay. Dane, let me take the first question, and I'll ask Rafael respond to the second one. In terms of when the chromosomal anomaly occurred, that's an important question. But there is a reasonable hypothesis that we believe that is making us say that this could be from the gene editing, nuclease 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 giving -- going too much into the details of how much we know at this point.

Yes. And with regards to the trial design, as David mentioned before, these products have been all approved based on single-arm trials, including the most recent ones, both in lymphoma and the most recent one in multiple myeloma. We believe that we will have the same -- follow the same path, particularly given the fact that we're an off-the-shelf therapy with the advantages of licorice, and the ability to treat every patient and the differentiation with autologous products. So at this point, that is our expectation and our belief that this will be a single-arm trial.

Your next question comes from the line of Robert Burns from H.C. Wainright.

This is Mitchell on for Robert. 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 post CAR T setting that you anticipate pursuing?

Okay. So in terms of any changes in the clinical study design. Obviously, we will not go into that kind 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 the patients as well as asking many questions that could advance the field of allogeneic CAR T therapy.

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

Yes. I think it's hard to sort of speak to that ahead of the congress. I mean we want to reserve the ability to present this and keep the confidentiality until the time lines of the congress. So apologies for dodging the question, but stay tuned, you'll see the answer.

And ASH is only 4 weeks from now.

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

Maybe a little more color on the planned Phase II 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 2 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?

Yes. As I said before, I mean, without going into the details of how we will define the -- design the trial, we plan to have a single regimen in the study. So we don't plan to have a single dose and consolidation dose would be a single regimen in a single-arm trial. So that's as far as we can go with regards to study design.

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

The last question around the ALLO-605, the TurboCAR T. Could you share with us some of the type of the cytokine armory you're using to further improve the cell toxicity of the cells. And also, could you remind us for your clinical trial, are you seeing consolidation therapy? And also, are you also combining with GSK for the ALLO-605?

Yes. So the TurboCAR study, we're extremely excited about that. The potential of these CARs to actually expand the grease exhaustion and have greater antitumor activity and potentially perhaps be able to use fewer cells. These are tieing signaling that are generally done a chain cytokines that are tropic to T cells and we haven't gone into the details of the specifics, but you can imagine that these are -- the kind of cytokines that one sees to recover homeostasis after lingo depletion.

We may decide to use GSI that is a decision that hasn't been made yet. And 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. That concludes our question-and-answer session. I would like to turn the conference back over to management for any additional comments.

Thank you again for joining the call today. We are deeply committed to patient safety and continuing our work with 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 that we, as a 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, you may now disconnect.

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.