Hello. Thank you for standing by for this conference call. At this time, all participants are in a listen only mode. On today's call, there will be a question and answer session. Thank you.
Please be aware that today's conference call is being recorded. I would now like to turn the call over to Christine Casciano, Chief Communications Officer, Ms. Casciano, please go ahead.
Thank you, operator, and thanks to all of you for joining today on short After the market closed today, Allogene issued a press release that provides a clinical update on our AlloCAR T program. The press release and today's webcast are both available on our website. Today's call will be led by Doctor. David Chang, our President and Chief Executive Officer. During the Q and A, he will be joined by Doctor.
Rafael Amato, Executive Vice President of Research and Development and Chief Medical Officer and Doctor. Eric Schmidt, Chief Financial Officer. We will do our best to get to as many questions as possible. As such, we ask you to limit questions to 1 per person, so we can get to as many as possible. 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 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. We recently issued a press release indicating that the FDA has placed a clinical hold on all our AlloCAR T clinical programs based on a single patient case are in the ALPHA-two trial. While this is disappointing for Allogene, the field as well as Many of our stakeholders, I want to reinforce our conviction in the opportunity ahead. Between myself and Rafael alone, we have more than 15 years of experience in developing engineered cell therapies. Although this new and exciting field of innovation is unchartered, we know we are forcing the way in allogeneic cell therapy As we strongly believe, it will be the next therapeutic option for patients.
In the same way, some of us encountered and addressed challenges with bringing 1 of the first autologous CAR T therapies to market. We feel confident We will do the same here at Allogene with Allogeneic CAR T products. The data generated from ALSOS file supports a favorable clinical profile for ALLO-five zero onea in patients with large B cell lymphoma, Which underlies our mission to provide allogeneic CAR T therapies faster and more reliably to patients suffering are from some of the most difficult to treat cancers. We also recognize that today's news elicits have a lot of scientific questions that have yet to be answered. Our team is working diligently to address these questions And we are committed to communicating updates in a timely fashion.
While we are not in position to provide a lot of answers today, We are working through this with a clear intention and the commitment to support the overall development of allogeneic CAR T therapies for cancer. So let me provide some background on this clinical hold. We reported information to the FDA on a patient with stage 4 transformed follicular lymphoma and CMIC rearrangement, whose cancer was refractory to 2 are in line with immuno chemotherapy and additional radiation therapy. The patient was not able to receive an autologous CD19 CAR Following infusion of ALLO-five zero one A, the patient experienced Grade 1 CRS and Grade 2 iCAN, which required a course of high dose steroid therapy. The patients subsequently developed progressive anti cytopenia And bone marrow biopsy showed atopic anemia and the presence of ALLO-five zero onea CAR T cells with a chromosomal abnormality.
Early translational data shows that the CAR T cells expanded speaking on day 28 and was undergoing contraction thereafter. The patient had a partial response to ALLO-five 01A and subsequently underwent allogeneic stem cell transplantation. Prolonged cytopenia requiring Rescue stem cell transplantation has been reported in Autonomous CAR T therapies. An investigation is underway to further characterize observed abnormality, including any clinical relevance, Evidence of clonal expansion or potential relationship to gene editing. As we work with FDA to resolve this situation, the FDA continues in parallel to actively review End of Phase 1 material submitted in anticipation for an ALLO-five zero onea pivotal Phase 2 trial.
I want to reiterate that patient safety is our highest priority and we are committed to working closely with the evaluate any potential clinical implications from this single patient report to determine next step for advancing ALLO-five zero one A and our clinical programs. Importantly, Allogene has sourced more than 100 patients with its gene edited AlloCAR T product. We believe the data generated from ALPHA supports a favorable clinical profile for ALLO-five zero one A in patients with large B cell lymphoma And look forward to presenting updated data later this year. We are grateful for the partnership with the patient community, Clinical investigators, our Scientific Advisory Board and FDA as we work diligently toward understanding any clinical significance of these findings to support the ongoing development of allogeneic CAR T therapy for cancer. I'd like to take the opportunity to thank our employees, our partners, Our trial participants and our clinical investigators for their continued hard work to advance our AlloCAR T products.
We are privileged to be at the forefront of an incredibly innovative and important will now face a complex field as we look forward to continuing to work with FDA to promote our efforts. We could not be more proud of the work accomplished each day by our team members, who are committed to bringing the first allogeneic CAR T therapy to the Many patients in need. We will open the call for questions.
And your first question comes from the line of Salveen Richter from Goldman Sachs. Your line is
open. Thanks for taking my question. Did you find the chromosomal abnormality in the manufacturing lot Was dosed for this patient or in other lots?
Yes. So The question about whether this was seen in the manufacturing lot or our lot other lots, Our lots before they are released undergo extensive and I should say, state of the art release testing That includes assessing any kind of chromosomal and malignancies. So certainly, all the labs that were used in the clinical trials passed the release test. But given the finding, we are investigating every possibilities That could have contributed to the observed finding in this single patient.
Thank you. And your next question comes from the line of Mark Frahm from Cowen and company, your line is open.
Thanks for taking my questions and sorry for the snooze. When you look at the bone marrow biopsy, do all of the ALLO-five zero one cells that are 501A cells that are present have the abnormality? Or is it just some of them? And in that case, what percent are you able to detect it in that circulating samples of when you talk about expansion and contraction.
Yes, this is Rafael.
In the Cardiophistic analysis is a fraction of cells that are detected with this abnormality. The CAR T cells peaked and then started to contract and obviously that includes that population. But we need to look more carefully with molecular assays to really know the kinetics of the cloning question.
Okay. And are you people say with the abnormality that's being detected, is it At the site of the integration of the lentivirus, is it involving is it similar to where you were cutting with the Talon? Just
We know the chromosome location. It's chromosome 14. Other than that, in terms of where the changes occurred is currently under investigation.
Okay. Thank you.
And your next question comes from Michael Yee from Jefferies. Your line is open.
Hi. We had 2 related questions, so maybe that counts as 1. But the first was, what in your opinion is the ultimate Clinical ramification of what would happen and what could happen here, given the chromosomal abnormality. And then can you talk about what would happened because I thought the cells would eventually go away. So maybe just talk about a little bit about the clinical implications and what would come about from this that would be concerning given the risk benefit of the actual drug.
Thank you.
Yes, Mike, let me try to answer the question. This is It's still very early and I will not be able to answer all the questions. We are trying to First of all, whether this is a clinically relevant finding. Obviously, this is observation that has been made. And our approach is trying to better characterize what exactly happened to the chromosome And that may require some additional investigation.
And as previously asked by Salveen, We are also looking to see when these changes may have occurred. I mean, so those are some of the ongoing investigation. And let me also reiterate, this is a single case report out of more than 100 patients that we have tried. And this is not something that we normally look for, because most patients do recover And CAR T cells disappear from the patient's body. So there is many unknown questions and we are working diligently
yes, the next question comes from the line of Jason Gerberry. Your line is now open. Hey, guys.
Thank you for taking my question.
I guess, I'm just trying
to get my head around,
it seems like there's Potentially a lot of confounding variables here. Patient got higher immune chemotherapy, radiation, iDose steroid, potentially got conditioned For autologous CAR T, but didn't get that autologous CAR T. So just wondering if you can provide any context for some of these confounding variables and You're going to adjudicate that. Thanks.
Yes. I mean,
There are a lot of factors that could have contributed to cytopenia. All these patients are heavily treated, as you know. And as David remarked, they couldn't make a graph, which means the lymphocyte count was low Well, another lineages were also low. So whether or not that contributed to the overall cytopenia It's really speculation, but in general, patients that are heavily pretreated, That has been associated with cytopenias in the past. Cytopenias are seen in the autologous setting.
This has been looked at and there are series that have been published. It's actually in every label of the reapproved product. And there have been instances where Queue with palmarotransplantation has been required. And so it's not really unfortunately that uncommon to observe
And your next question comes from the line of Michael Schmidt. Your line is now open.
Hey, guys. Thanks for taking my question. I guess, Armando, when you go about your clinical and your Your investigation into this, I guess, what are possible or hypothetical explanations that for that chromosomal abnormality that you will look into? And what do you Thank you. You want me to do eventually to potentially move the chemical holode?
Yes. Michael, that's a great question. Let me just sort of talk about our some internal working hypothesis. I mean, obviously, when you encounter problems like this, we have to be methodical and we have to make a science driven approach about finding out how this happens. Having said that, one has to understand that There has been several number of publications, in fact, With the use of gene editing nucleases, most normal structural changes can occur.
These changes include simple things as non homologous end joining as well as large chromosome deletions, Sometimes translocations or inversions. So that is The investigation that we are doing. And the second one, and I think this is something that not many in the field appreciate, But T cells, as they undergo rapid expansion, it has been well documented That they acquire changes that includes mutations or deletions or inversions And certainly, CAR T cells, as they encounter antigens, they can undergo pretty rapid expansion. So there are these 2 different sort of somewhat different hypothesis and that is currently our main focus of investigation.
Very helpful. Thanks. And then I guess, do you have a timeline or an FDA meeting Coming up and how should we think about ultimately the resolution of this?
So that's this is a very dynamic period. I mean, certainly, we are communicating the information as we are learning from what FDA has told us. We need to better understand FDA's questions. And Hopefully, with that, we will better understand what needs to be done to come out of the clinical hold. Okay.
Thank you.
And your next question comes from the line of Luca Eze of RBC Capital. Your line is now open.
Great. Thanks so much for taking my question. So maybe wondering if you have done any RNA seek analysis on the sample. I wonder if you can provide any color on whether the chromosomal abnormality actually has led to any change in the transcriptome of the cell? And then maybe bigger picture, obviously, you're doing an Extensive investigation in my mind, worst case scenario is that you see some evidence of clonal expansion.
Wondering if you can articulate what would be the best Case scenario, out of this analysis. Thanks so much.
Yes. Luca, this is a great question. Yes. And as you can imagine, there's a whole host of assays that are taking place and Others that will take place once we have induction today. So we want to sort of reserve any sort of opinion on results of assays for what types of assays we're doing until we actually have a dialogue with FDA know exactly how to address their concerns.
So please stay tuned. Apologies if I can't really answer your question fully, but We will give you information as soon as we have them.
Got it. Thanks so much.
Your next question from Marc Biedenbach of Oppenheimer. Your line is now open.
Hey, good afternoon. Thanks for taking the Question. David, I'm just wondering if you're seeing any potential need to revisit the notion of a suicide switch technology with your AlloCAR cells sort of like what you had built into the ALLO-five zero One version before switching to ALLO-five zero one A, if you see value in potentially Reintroducing that sort of technology into the rest of your product line. Thanks.
Mark, let me take that question. I mean, Suicides, which always has been a consideration with any CAR T therapy from the early days of autologous CAR T therapy. I mean, I think In the CD19, the question around the usefulness of suicide switch, I think that has been Never really shown to be necessary for the CD19. And so with that Well, in terms of what else we will be doing, I just want you to understand that this is very early Sort of stages of investigation and we will follow-up with additional communications and thoughts as we better understand what's going on with
Okay. Thanks for taking the question.
Your next question from Raju Prasad ask William Blair. Your line is now open.
Thanks for taking the question. I think the hold is across all trials. Can you just give us a sense of the maybe just broad sense of the release criteria that you have underway? And is it similar across all trials? Or are there
Raj, let me take that question. I mean, at this point, it's too early for us to comment About how FDA's are thinking. It was a bit of a surprise that they placed a clinical hold on all our clinical trials, but we have find that are from the FDA. Sorry that I can't give you any more clarity on that answers to that question.
And your next question from Ben Burnett of Stifel. Your line is now open.
Thank you very much. I wanted to follow-up on an earlier question, just around the notion of the suicide switch and getting rid of product if needed. I guess, when this was discovered, like what was the clinical course of action and were steroids given? And I guess if they were, were they affected by clearing the product?
As we said in the prepared statement, There was cell expansion and after we picked on day 28, it was contracting as Frequently seen in the CAR T cell expansion profile. And essentially, the observation is made on very limited number of new cells From the bone marrow biopsy that was initiated by the investigators. So that's what we know and we will let you know more as we Better characterize the genetics of the cell expansion. Is there a next question?
Yes. Next question from Attica Goodward of EME. Your line is now open.
Hi, this is Bill. I'm on for Africa. I'm sorry about the unfortunate news. I had a question regarding the Day 28 expansion. Could you remind me if that's typically seen or is that within the range of the mean or do you think this chromosomal abnormality could have contributed to it shifting away from the
I'm seeing in our product. And in fact, I would say this is very similar and representative of 4 1BB containing chimerganetine receptor construct.
Thank you, David.
All right. Our Our next question is from Dane Leone of Raymond James. Your line is now open.
Hi. Thanks for taking the questions on obviously a tough revelation. Obviously, the patience here is the So I just had two questions. One, is there any at least initial evidence in terms of The disruption around the chromosome for the TCR knockout on chromosome 14. And then the second question would be, Can you just clarify a little bit more what is initially the concern around the clinical linkage here given The patient probably had fairly degraded bone marrow ahead of ever receiving the therapy or the therapy.
Is there some sort of evidence that we've seen that the CAR C positive cells that were put into the patient are are somehow attacking the bone marrow or some other phenomenon that would give us pause for clinical concern here. I think we're all kind of struggling with that link Thank you.
Yes. In terms of the reason for bone marrow biopsy, Our understanding was that was done to evaluate pancytopenia that was observed in this particular case. And I would say That's a routine clinical investigation when somebody has a lower blood count. So I don't know whether I can add anything more. In terms of the first question, can Can you just remind me again on the first question you had, Dane?
Yes. Just if the edit The space around the edit presumably on chromosome 14 for the TCR knockout, is that in any relation spatial relation to the chromosome or imatinib
At this point, we do not have enough information on where the changes occurred on the chromosome. I mean, that's part of our initial attempt to find out the change where the chromosome Flipping occurred. And once we have that, we will have much better understanding. But stay tuned. We are working feverishly to answer some of these questions.
Okay. Thank you.
Thanks, Nate.
And our last question from Kalpi Patel of B. Riley. Your line is now open.
Hi, this is Yuan on for Calcutta. Thank you for taking our questions. So for the reported pancytopenia, is it treatable through stem cell transplantation? And our second question is that, So for this abnormal T cells we observed here, is there a way to eliminate them like using chemo or may be another line of treatment. Thank you.
So if I understand correctly, Your first question was where transplantation is a treatment for aplastic anemia, which is the answer to that is yes. There's medical treatments and then there are transplantation treatments. And the caring physician, the physician that's here for Specialists chosen to develop bone marrow transplantation. With regard to the second question, can you please repeat it?
Yes. So is there a way to eliminate this observed abnormal T cells?
Oh, I see. Yes, thanks for that. As we've been saying several times, The cells have contracted, and they are becoming very detectable, But the patient has already undergone conditioning for the bone marrow transplantation. So those cells are probably eliminated with the
and that concludes our question and answer session. I would like to turn the conference back over to management for any additional comments.
Yes. This is Dave Chang. Thanks for joining us today. As I've said, we believe we have a tremendous opportunity to deliver our 1st in class therapy for patients. Our team is working tirelessly and we are committed to communicating with transparency as we have more information to share.
Operator, you may now disconnect.
Thank you. Ladies and gentlemen, thank you for your participation in today's conference. This does conclude the program and you may now log off and disconnect.