Hello. Thank you for standing by for this conference call. At this time, all participants are on a listen only mode. After the speaker's presentation, there will be a question- and- answer session. To ask the question during the session, you will need to press star then one on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star then zero. I would now like to turn the conference over to Christine Cassiano, Chief Communications Officer. Ms. Cassiano, you may begin.
Thank you, operator, and thanks to all of you for joining our call this morning. Before market open, Allogene issued a press release announcing that the FDA has removed the clinical hold on all of our AlloCAR T clinical trials. This press release, as well as today's webcast, are available on our website. Here with us to discuss today's news will be Dr. David Chang, our President and Chief Executive Officer, and Dr. Rafael Amado, Executive Vice President of Research and Development and Chief Medical Officer. During the Q&A, they will be joined by Dr. Eric Schmidt, Chief Financial Officer. We know this is a busy day for all of you, and we will do our best to get to as many questions as possible. As such, we ask you to limit questions to one per person. 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, among other things. These forward-looking statements are based on current information, assumptions, and expectations that are subject to change. A description of potential risks can be found in our most recent SEC disclosure document. 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. Good morning to you all, and happy New Year. Today, we are excited to share the news that the FDA has lifted the clinical hold on all of our AlloCAR T programs. You may recall back in October that we reported a single case of a chromosomal abnormality observed in a patient treated in our ALLO-501A phase I trial. The investigation into the chromosomal abnormality concluded that the abnormality was an isolated event that developed in the patient after the cell product was administered. It was unrelated to TALEN gene editing or Allogene's manufacturing process and had no clinical significance. Specifically, the abnormality was not detected in any manufactured AlloCAR T product or in any other patients treated with the same ALLO-501A lot.
It involved regions of the T cell receptor and immunoglobulin genes known to undergo rearrangement as part of the T cell or B-cell maturation process. We are grateful that the FDA, which has been highly engaged, expeditiously completed its review and agreed that we have satisfactorily addressed all clinical hold issues. Since our inception, we have invested heavily in product science and manufacturing. This core competency allowed us to complete our analysis and respond to the FDA's question in less than 2 months, with the hold being lifted in 3. Having concluded our investigation, we are even more confident in the fidelity of our TALEN gene editing platform, our overall approach to manufacturing, and the caliber of our manufacturing and R&D teams to expeditiously handle any unexpected challenges. I would like to thank the team at Allogene, led by Dr. Rafael Amado and our Chief Technical Officer, Dr.
Alison Moore for their hard work to resolve this situation in a timely fashion. I would also like to thank our scientific advisory board and clinical trial investigators who supported us throughout this endeavor. Overall, while the experience is not one that we had wished for, it has served to enhance our knowledge and strengthen our resolve when encountering complex scientific problems. As such, I believe we are better positioned than ever to resume our goal of delivering allogeneic CAR T therapy to patients. Now, I would like to turn the call over to Rafael.
Thank you, David. The chromosomal abnormality was an anticipated finding, and we conducted a very thorough investigation into its nature and provenance. This was important work which has the potential to impact the entire field of engineered cell therapy. I'm very proud of our achievement and grateful for the tireless effort of our team to conduct an extensive investigation in two months and resolve the clinical hold on all our programs in just three months. This included the precise mapping of the chromosomal abnormality, the development of complex analytical assays, the analysis of large sets of clinical samples, and the interrogation of multiple manufacturing lots. Through our efforts, we were able to sequence the genetic regions involved in the abnormality and determined that it was unrelated to our manufacturing processes.
I believe our understanding of engineered cell therapy is meaningfully enhanced relative to where we stood just a few months ago. As we have gone through this exercise, we do believe that we're now advantaged based on the detailed learnings from this investigation and feel increasingly confident in our approach. We believe we're even better positioned to lead the field in bringing an AlloCAR T product to the market. Earlier today, we began notifying our clinical trial investigators that the FDA hold has been lifted. Clinical sites have been keen to reengage, and we look forward to working with the sites so that we can treat patients across our AlloCAR T development programs as quickly as possible. Allogeneic CAR T therapy is a rapidly developing field that continues to evolve both in scope and impact.
We are privileged to stand at the forefront of this incredibly innovative therapeutic area and understand that we will encounter novel findings which will challenge us as we pioneer this field. What we have experienced over the past few months in dealing with this situation is, in many ways, a microcosm of what the cell therapy field has experienced over the past 5-10 years. Learning curves are steep. The pace of innovation is fierce. Complex challenges will arise that require new levels of sophistication. The regulatory bar, especially as it relates to product quality, will continue to be raised. The companies that end up succeeding in this field will be those with the experience, talent and resources needed to meet these challenges. Having gone through this investigation, I am confident that the team at Allogene has the inimitable knowledge, experience and perseverance to lead.
Having achieved our objective of timely resolution of the clinical hold, we now must turn our attention to the greater goal of bringing AlloCAR T therapy to patients. As I have previously noted, the patient in whom the abnormality was observed was unable to receive autologous CAR T therapy and failed all prior regimens. This case highlights the very meaningful unmet clinical need in relapsed refractory non-Hodgkin's lymphoma. We look forward to concluding our end of phase I discussions with the FDA and plan to initiate our phase II trial of ALLO-501A in relapsed refractory large B-cell lymphoma around the middle of this year. The trial initiation will represent another step towards fulfilling our mission to provide allogeneic CAR T therapies faster and more reliably to patients suffering from some of the most difficult to treat cancers. With that, we will now open the call for questions. Operator?
Thank you. Ladies and gentlemen, as a reminder, to ask a question, you will need to press star then one on your telephone. To withdraw your question, please press the pound key. Again, that's star one to ask a question. Please stand by while we compile the Q&A roster. Our first question comes from the line of Tyler Van Buren with Cowen. Your line is open.
Hey, guys. Good morning and congratulations on the update. It's great news. Have two questions. The first one is you mentioned that you're now advantaged and in a better position to bring an AlloCAR T product to market. To that end, has the investigation prompted you to incorporate any additional screening measures to your manufacturing process or is it sufficient as it stands? The second one is, as you resume clinical activities, how do you envision the pace of enrollment moving forward? Have your priorities for enrolling certain clinical trials changed from three months ago?
Hey, Tyler. Thanks for those important questions. I mean, throughout, you know, this investigation, much of it was led by Rafael, so I'm gonna ask Rafael to respond to the both of those questions.
Thanks, Tyler. As I mentioned before and David mentioned as well, the investigation really didn't uncover any involvement of TALEN gene editing. And there was really no evidence of any other abnormalities in any of our products. We undertook very extensive testing across all 5 INDs. As a result, there are no new measures that we need to employ with regards to our processes or release assays or anything else with regards to manufacturing.
We're very pleased, you know, to be able to continue with the current process. With regards to the pace of enrollment, I don't think this issue really affects what will happen with regards to enrollment in the trial. We have continued throughout the process of the hold to engage with FDA on the design of the clinical trial and on the CMC issues, and that's been very productive. We continue those discussions, you know, towards launching the phase I study. The investigators remain very engaged, and as I mentioned before, that unmet medical need exists. We anticipate that enrollment will continue just as briskly as it has in the past years during our phase I study.
Tyler, as Rafael said, you know, this is, you know, relatively very clean removal of the clinical hold. There is almost no changes that we have to do in the manufacturing of our AlloCAR T products.
Okay, that's great. Thanks so much for the color.
Thank you. Our next question comes from the line of Mike Yee with Jefferies. Your line is open. Check to see if you're on mute.
Thank you. Good morning and appreciate the questions and the update. Hey, guys. We had two questions, but they're related. Can you talk to any monitoring or other amendments to your planned studies? Particularly managing patients or anything related to this event that may have to be implemented. Then going forward, should Wall Street expect that this type of event is plausible due to other external factors not related to TALEN or gene editing? Describe what is possible and is it material and disclosable if something happened again? Maybe talk to that. Thank you.
Michael, this is Rafael again. I mean, with regards to the impact on the studies, you know, the impact is minimal. Obviously, we are already, you know, as any gene editing program inform patients, and we have updated the informed consent as it relates to the potential for chromosomal abnormalities to occur. You know, other than that, there really hasn't been any impact with regards to the studies. In general, I think, you know, the broader impact to the field, you know, it is, you know, thankfully, at least in our case, really highlighting the fidelity of our TALEN gene editing technology.
You know, this is something that we were very gratified to see in that you know, we haven't actually had to make any changes, as I said before, because we could definitively identify these areas or breakpoint that were away from the TALEN site. You know, in general, you know, as I said, we personally don't have any more obligations regulatory-wise with regards to this event. Whether or not you know, there will be other repercussions in the field, I think remains to be seen with regards to you know, what may happen in the future.
Yeah. You know, Michael, the second question that you asked is a very important one. Let me just expand, you know, our response on that. When we, you know, found this, you know, learned about this finding, I mean, we knew immediately the potential impact of gene editing and chromosome changes. You know, not only to what we are doing as well, but also potential impact to the cell and gene therapy. I mean, one of, you know, the, you know, that's underlies, you know, why we took, you know, such an extensive investigation into, you know, what happened to that particular patient to really get down to the bottom of it. I mean, certainly, you know, the question about whether something like this will happen in other cell and gene therapy studies.
I mean, given the history and given that we are dealing with live cells, certainly the possibility is there. When it happens, I think what's important is how each company handles situations like this and come up with an explanation, that will not derail the entire field. Certainly our findings, I think, has a very little impact on what we do. Certainly the finding that this had nothing to do with our TALEN gene editing is very reassuring. Stay tuned on this matter, but this really highlights, you know, one of the importance of investing in the manufacturing, especially product characterization and quality assurance and quality control of the cell products.
Thank you.
Thank you. Our next question comes from the line of Salveen Richter with Goldman Sachs. Your line is open.
Thank you. Two questions here. One on the timelines for data across your portfolio, given the update today. Secondly, you know, in discussions with the FDA, as you were working through, the chromosomal abnormality and the assay work and so forth, what, I guess, standards have been set for, you know, the case where something like this may occur in the future?
Salveene, this is Rafael again. In terms of timelines for data, we obviously just came off a hold, and we are engaging with investigators, IRBs, clinical sites, and so on to resume our trials. I think it's difficult for us today to, you know, come up with specific times where, you know, data flow will come. We will commit to really getting back, you know, to the investor community, you know, with more details about that. Suffice it to say that we're, you know, putting full energy in getting these studies resumed and restarted. You know, with regards to chromosomal abnormality standards that may occur, I think, you know, obviously that is up to FDA to make decisions.
I think it will depend on the nature of the finding. You know, in our case, I think, you know, we were able to define precisely the nature of the abnormality and also the fact that this was naturally occurring process. You know, obviously there may be findings in the field of gene editing that may occur in the future that may require, you know, further investigations depending on their nature, the provenance of the alteration, et cetera. You know, this is a very nascent field, and it may evolve to the point that other assay release assays in the future may be required. But as a result of what we found, as I said before, there's really nothing else that we need to do, you know, based on this finding.
Thank you.
Our next question comes from the line of Jason Gerberry with Bank of America. Your line is open.
Hey, guys. Thanks for taking my question. So just to confirm, it sounds like this FDA discussion that happens before you start your pivotal for 501 is more of a check-the-box administrative type of hoop, and you would not expect any impact in terms of your ability to pool 501 data for purposes of, you know, as you think about a regulatory package. I realize you're not at a point where you can talk specifically about timelines, but there's a lot we expected to learn in 2022 about 715, either consolidation or GSI combo. Can you give us a sense, did you enroll many patients with those approaches prior to the clinical hold?
You know, assuming that you can get back and running some time in the first half, could we get a fulsome update by end of year to understand better your BCMA strategy? Thanks.
Jason, with regards to the FDA discussions, I mean, they have proceeded in a very thorough fashion, and it's been really collaborative. As you know, this is a co-development of ALLO-647 as well as ALLO-501A, and all discussions have taken place on both fronts, as well as, you know, very detailed discussions on CMC, which continue as David alluded to. Yeah, we are, you know, very enthusiastic and confident that, you know, we're gonna be able to arrive at a position where we can launch this trial.
In terms of the timelines for ALLO-715, we had begun enrolling as we had announced before, on the ALLO-715, on consolidation, as well as on the TurboCAR ALLO-605 programs. You know, they were put on hold and they're going to resume as soon as practicable. You know, hopefully, we will be able, as we said, you know, in 2022 to give an update, but as I said before, you know, it depends on, you know, how the pace of accrual is and how quickly we can resume the activities. Clearly there's a lot of energy, a huge unmet need and a huge desire from the myeloma community to, you know, put patients in this trial.
I'm optimistic that we will be able to continue these trials very briskly in terms of accrual.
Okay. Thank you.
Thank you. Our next question comes from the line of Mark Breidenbach with Oppenheimer. Your line is open.
Hey, good morning and thanks for taking the question. Congrats on the speedy resolution of the clinical holds, of course. Kind of a two-part question from me. First of all, can you use existing stockpiles of AlloCAR T cells as your clinical sites begin enrolling again, or will new batches need to be manufactured? The second part of the question is a little more science-y. If I'm understanding correctly, it sounds like the issue was related to a V(D)J recombination error. If that's the case, I'm wondering if you can give us any more color on what type of recombination error occurred, and more importantly, why a V(D)J recombination would be occurring in relatively mature T cells that have been infused into a patient.
My understanding is that this process usually it occurs or is restricted to very, very early stages of T cell maturation. Thanks for giving any color on that if you can.
I'll answer, you know, these questions, Mark. I think they're incredibly insightful, by the way. You know, with regards to new batches, you know, obviously we stopped treating patients and we tested all the batches for the presence of the chromosomal abnormalities, and we believe that you know, these batches are ready to be used again. You know, we will continue to proceed with the material that we have. We will make material as needed, but you know, the old material is still viable.
I think the question about, you know, whether this is something that occurs, you know, obviously in the thymus only. There is actually plenty of literature that rapidly proliferating T cells and B-cells can rearrange the T cell receptor and the B-cell receptor even if they're post-thymic and they're mature cells. Alterations can occur even spontaneously, actually, in patients as a result of this. These are fragile areas of the chromosome that are subject to rearrangement. You know, the machinery that actually exerts these rearrangements is active in these cells, but it's only upon proliferation. It's not something that hasn't been described in the past. Even though most of it occurs pre-thymically, it does occur also in mature T cells.
Okay. Super helpful. Thank you.
Thank you. Our next question comes from the line of Michael Schmidt with Guggenheim. Your line is open.
Hey, guys. Thanks for taking our questions. I guess I had one on the planned registration study for 501A that it sounds like you're getting ready to initiate that in the middle of the year. I guess as we think about the study, perhaps relative to the ZUMA-1 trial or the TRANSCEND NHL study from Celgene, you know, what are some of the differences in patient population that you would anticipate in your study compared to those? And are there enrollment criteria that are perhaps different or similar to those studies?
Michael, the population would be relapsed refractory across a variety of aggressive lymphomas. You know, I think it will look very similar to the studies that led to the initial approvals of liso-cel and axi-cel. We are aware that, you know, there are, you know, patients that may move into second line and we, you know, plan to continue to expand the program as time goes on. That there will still be, you know, sufficient patients with relapsed refractory disease that will be able to come into the study. There may be other, you know, subsets of patients with refractory disease that may be eligible as well.
In general, it will be the population that you have accustomed to seeing in the trials that led to the initial approvals.
Great. Thank you.
Thank you. Our next question comes from the line of Reni Benjamin with JMP Securities. Your line is open.
Hey, good afternoon, guys. Thanks for taking the questions and congratulations on the update and lifting of the clinical hold. Rafael, you mentioned that there were updated informed consent documents, and I was wondering, kind of, outside of this, do you need to monitor, you know, every new patient now, you know, for something like this going forward? I guess related, how comfortable do you feel the FDA is with this finding such that, you know, if they saw it again, they would not put you, let's say, on a clinical hold?
Do you feel that, you know, the discussions have been more along the lines that, you know, they're kind of saying, "Well, let's see how, you know, the remaining clinical trials go and if something happens, we would want you to get to the bottom of kind of explaining why it might be happening.
Yeah, great questions. I think with regards to the first one, the answer is simple. We don't have obligations, you know, beyond the ones that we already have to monitor patients. We will obviously, if something occurs, like another finding occurs, we will be able to go back and, you know, do the work that's required in collaboration with FDA. As a matter of course, you know, beyond changes in informed consent, there are no changes in terms of monitoring. I think with regards to the confidence of FDA. FDA just like us, you know, found this as a pretty novel finding, and obviously it's in the context of gene editing.
You know, when you find something for the first time, it's important to actually try to get to the bottom of it. You know, we understood their concerns, understood their questions and worked pretty diligently to, you know, resolve all these findings. You know, particularly, you know, what is the provenance of the findings? Where did it arise? Are there other implications for other patients? What about other batches? You know, those kinds of questions, which I think are fundamental to understand. In the future, I think again, you know, it will depend on the nature of the finding.
You know, I believe that, you know, if there is a finding that is new and concerning with regards to the potential, you know, for this to impact manufacturing particularly and impact patient safety, you know, there will be, you know, a response, you know, from regulatory authorities and, you know, but the nature of the finding that would lead to that and the nature of the questions, I think, you know, it will, it's still to be defined. As I said, you know, we're all learning as we go along and we've learned a great deal, you know, from this finding.
You know, hopefully, even though this wasn't a pleasant situation to be on hold, you know, we are now, you know, pretty strong with regards to what we've been able to learn. Again, you know, stay tuned. You know, when you start in a new field, there could be new findings that occur, and I think the reaction of both regulators and companies will be according to the nature of the finding and the potential consequences.
Great. Thanks for taking the questions.
Yeah.
Thank you. Our next question comes from the line of Dane Leone with Raymond James. Your line is open.
Hi. Thank you, and congratulations on getting the clinical hold resolved. Two quick ones from me. Can you maybe just give us a heads up in terms of when you might be able to have a handle on providing a timeline for IGNITE and TRAVERSE, specifically, and when we might be able to see first data from there? Whether maybe on your fourth quarter earnings call you might be able to clarify timelines. Then, second question, just housekeeping actually from Ash, but were you guys ever able to resolve whether any patients in ALPHA2 had been previously treated with CD19 CAR T? I know that had been outstanding for those patients that had prior CD19, but I think your team was looking into that. Thank you.
Yeah, with regards to the timelines, as I said before, it's you know difficult to say exactly you know when we will know about IGNITE and TRAVERSE. We're extremely excited about both trials and I think the resumption hopefully will be brisk. There's a lot of interest from investigators, as I said before. We will present data when, if we have a meaningful data set, and as soon as we think you know that is the case, we will do it in the context of a scientific forum.
With regard to, you know, the ALPHA data set, there were patients that had received auto CAR T therapy, one or two patients, but in the consolidation, we were able to, you know, determine that there were no patients there that had received actual auto CAR T therapy. There was CD19-directed therapy, but not AlloCAR T. That's sort of the outcome of the investigation in that consolidation group.
You know, Dane, you know, let me just add on. I mean, I know that many of you have, you know, questions about our clinical study timeline. I just want you know, to realize that we just came off the clinical hold. It's just too early for us to map out the study reactivation and enrollment projections and data communication. So just give us a little more time to sort some of those operational issues out, and we will update the timelines on our solid tumor programs as well as what we are doing in the multiple myeloma space. Certainly with the pivotal study, we are projecting that the study will start midyear 2022.
Thank you. Our next question comes from the line of Luca Issi with RBC Capital. Your line is open.
Oh, great. Thanks so much for taking my questions and congrats on kind of going off the clinical hold. I have two quick ones. One on the science. Wondering if you can comment on what percentage of the cells collected from the biopsy actually had the abnormality. I think you mentioned in the past that it was just a minority of the cells collected, so wondering if you can share the exact percentage today. Maybe related, wondering if you can comment on the nature of the abnormality. Was this a translocation, a deletion, an inversion, a substitution? Like any color there would be super helpful. Then maybe related, obviously your PR mentioned the starting pivotal trial is pending FDA discussion, and I know this question was asked before, but can you just maybe elaborate on what's gating to actually start that trial?
Thanks so much.
Thank you, Luca, for the questions there. You know, also very good questions with regards to the particular percentage of cells that carry the abnormality. There are a lot of details that we uncovered through the process. I can tell you that it was a percentage of the lymphocytes. You know, it wasn't all the cells in the patient. With regards to the evolution, the number and how it evolved over time, you know, all I can say is that we investigated this pretty thoroughly with pretty precise assays, and we don't want to jeopardize our ability to be able to publish this, and we're working pretty quickly to actually try to get this in the public domain through scientific press.
The other questions with regards to FDA discussions, you know, there are discussions across both clinical fronts and CMC fronts. Again, very happy that FDA continues to be engaged during the hold, which is truly important, because you know, this sort of speaks of their interest in us, you know, being able to get these programs into registration on file. We are advancing some of our manufacturing work streams. We're you know, planning and identifying new clinical trial sites, and all these activities we anticipate are gonna take us to midyear to complete. There are, as you know, a lot of CMC issues and the CMC bars, as said in my prepared remarks, is going up as well.
We're opening discussions with, you know, what it would take to actually, you know, start this study so that, you know, we don't have any CMC issues during the conduct and eventually when we get results and are ready to market the product.
Awesome. Thanks so much, Rafael.
Thank you. Our next question comes from the line of Raju Prasad with William Blair. Your line is open.
Thanks for taking the question, and congrats on the resolution of the hold. I wanted just to get a clarification on the regulatory outlook on chromosomal translocation frequency. I recall when kind of the hold was initially put into place, that was kind of a big discussion point. Can you maybe just give some context on the frequency of chromosomal translocations that are in your release criteria, as well as kind of how the regulatory body looked at that with regards to the resolution of the hold? Thanks.
Yeah, Raju, let me take that question. In terms of, you know, product release criteria, you know, we, you know, haven't really gone into any of the details on that. That's an evolving area, and we are working closely with FDA as we advance the clinical program. I mean, certainly you may or may not understand the release criteria that evolve as we have more experience from the product manufacturing. That certainly was an experience that I had when I was developing axi-cel or Yescarta at Kite, and we certainly expect a similar sort of evolution of how we set the, you know, release criteria. So, that's that. Sorry, what was your second question?
Just, a commentary on the regulatory outlook on translocation frequency.
Yeah, I mean, I think, you know, translocation, you know, certainly, you know, those are the ones that gets monitored, and certainly we have been able to, you know, keep all those changes, in the, you know, in a very well-controlled manner. So I don't really expect, you know, that to be, changing in any significant way. I mean, certainly, you know, what we have been doing is, you know, refining the assays to better characterize those events, and I think those are all moving in the positive direction. Another thing that, you know, I want to sort of emphasize is that, you know, allogeneic CAR T, you know, you may recall that our strategy of lymphodepletion is a transient lymphodepletion to allow cells to expand and carry out the antitumor effect.
By nature of our lymphodepletion, when the patient's immune cells reconstitute, and we expect this to occur in a period of, you know, 6-8, you know, maybe extending up to 12 weeks. In a relatively short period of time, immune system of the patient will reconstitute. When that happens, as the body normally does, you know, foreign cells such as allogeneic CAR T cells that we infuse to the patient are expected to be eliminated by the patient's immune system. Let's not forget about that very important safeguard that is intrinsic to how we are delivering the allogeneic CAR T therapy.
Great point. Thanks, Dave. Thanks, team.
Thank you. Our next question comes from the line of Kalpit Patel with B. Riley. Your line is open.
Yes. Hi. Thanks for taking the question. Now that you have precisely defined the nature of the abnormality, can you comment if you find examples of similar types of case reports historically with auto CAR Ts or any gene therapies, for example? If there are no known case reports, can you comment if you expect the rates of the abnormality to be similar between all types of CAR Ts? Thanks.
I'll take the question. In the literature, in the cell therapy literature, there is really not a lot of data with regards to this. You know, that's why my remarks before that this was kind of a novel finding, you know, that both regulators and us wanting to understand. You know, certainly there's been case reports of integration in particular areas of chromosomes have led to high persistence, and those have been described particularly by the UPenn group and so on.
In terms of chromosomal abnormalities, you know, it's not something that regularly people check for other than, you know, in the gene editing space, as David was saying, the translocations that are expected, those we obviously check for, as far as release criteria. Other abnormalities, you know, it's not something that people normally look at. Having said that, there are data in the literature about chromosomal abnormalities that spontaneously happen in patients, you know, as the immune system reconstitute. This is, you know, a normal process. These cells tend to be eliminated and, you know, those papers can be found, you know, in descriptions of both case reports and other series.
It's you know, not very abundant literature, but also something that really has been described as a normal process without any clinical consequences.
Okay, thanks for taking the question.
Thank you. Our next question comes from the line of Ben Burnett with Stifel. Your line is open.
Hey, thank you. Just a quick question from me. For the pivotal phase II study, I guess just given some of the results in the ALPHA2 in patients previously exposed to CD19-directed therapies, I guess can you talk about enrollment in the phase II pivotal, and will that exclude those patients that have previously seen CD19 therapies?
Yes, Ben, this is Rafael. Based on our experience and also even the oncologist experience with regards to retreatment, we believe that these patients do not benefit significantly from retreatment. We plan to exclude these patients going forward in the pivotal trial.
Great. Thank you so much. If I could just ask one other kind of follow-up question around the discussion of the abnormality. And I guess just this notion that it occurred as a result of rapid T cell proliferation. Is it your opinion that this is just going to be a known risk the field has to live with? Or I guess is there any appetite or push by the FDA to maybe s eek a next-gen version of CAR T cells that result in perhaps more controlled or slower proliferation.
You know, Ben, you know, let me take on that question. You know, obviously this is, you know, something that, the field is learning. I mean, I think the big distinction that has to be made is whether this kind of process is happening in the body, you know, and, you know, in a normal setting. Certainly our investigation and review of the literature suggests that, events like this normally occurs in the body. Whether we like it or not, somatic cells such as T cells are known to undergo changes, including some, structural changes to the chromosome. We believe what we have uncovered is really, you know, such a process, and as it happened, it happened in the AlloCAR T cells because that's where we are looking for this kind of event.
As Rafael had said, you know, these changes could be occurring in patients' normal T cells. We know from the way the body reacts. I mean, you know, these don't really have any clinical consequences. I think these are the important learnings. Personally, having been involved in this field for the last decade, I don't think this should really have any significant impact. I think, you know, what is gonna sort of ease the situation even more is being able to characterize this and, you know, provide some kind of analytical assay to answer, you know, some of these important questions. You know, going forward, stay tuned.
I mean, certainly from this experience, we mapped out the process and how to do it, and we will continue to do so if events like this happen in the future. I do not think it will have the consequence that we have experienced, where we were placed on a clinical hold for the entire program. Certainly, I hope that FDA also understand these nuance of the cell therapy and manage the situation properly.
Okay. Very helpful. Thank you.
Thank you. Ladies and gentlemen-
All right.
Thank you. That concludes our question- and- answer session. I would like to.
Yeah, yeah. Before we conclude, let me just, you know, make a final remark. You know, I just wanna thank everybody for joining us today. As pioneers in this innovative field, we expect to be the first to encounter rare and unexpected findings as we have experienced over the last three months. We have dosed more than 130 patients to date with our gene-edited AlloCAR T products and have reported our extensive safety experience at several medical conferences. Our experience, combined with the results of this investigation, make me more confident than ever about the future of allogeneic CAR-T therapies. Our team is eager to continue our work with all our partners as we resume study activities and look forward to a productive 2022. Thank you very much.
Ladies and gentlemen, that concludes today's conference call. You may now disconnect. Everyone, have a wonderful day.