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spk21: Hello, thank you for standing by and welcome to Allogene Therapeutics' third quarter 2021 conference call. At this time, all participant lines are in listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone keypad. Please be aware that today's conference is being recorded. I would now like to hand the conference over to Christine Casiano, Chief Communications Officer. Ms. Casiano, you may begin.
spk12: Thank you, Operator, and welcome to all who have 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. A description of potential risks can be found in our earnings press release and latest SEC disclosure documents. There are caution 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.
spk02: Thank you, Christine, and good afternoon. In October, we communicated that the FDA had placed a clinical hold on our Allocarti clinical programs based on a chromosomal abnormality observed in one patient in Alpha-2 trials. Although we have been unable to treat patients while the hold is in place, multiple other work streams at Allogen continue, including preparation for a Phase II pivotal trial on Allo501A, advancement of our Cell Forge 1 manufacturing facility, and all our preclinical work on solid tumor targets and next-generation technologies. On today's call, we will share a brief update on the clinical hold and perhaps even more importantly, the ultimate reason that we remain committed to advancing our platform, our data, and the potential impact to patients in need. Let me first start with what's on top of mind. Since we announced the clinical hold on October 7th, we have been actively engaged with the FDA in discussions that we hope will lead to a timely resolution. We are extremely appreciative of the time and attention that the FDA has devoted to this matter, which we believe has implications not only for the field of allogeneic cell therapy, but also the broader field of cell therapy. I'm also grateful to our team at Allogene, which are making great progress in generating information for us and the field to understand and properly address the chromosomal abnormalities observed in our patients. The FDA's stated mission is to ensure the safety and efficacy of medical products, but the agency has also been mandated by Congress to expedite product development. As FDA leadership has shared at recent public forums, they have identified the development of allogeneic CAR-T derived from healthy donor cells as a potential way to increase access to the therapy and decrease manufacturing time and cost. We recognize the FDA's responsibility to ensure patient safety while supporting innovation. The FDA has continued its review of our end of phase one material submitted in anticipation for a potential allofibro 1A pivotal phase two trial. From Allergen'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 re-initiation of our trials and view our Allocarti product as an important therapeutic option for patients, calling out how many of their patients cannot wait for the delivery of Atalas-Carti cells or don't want to risk manufacturing failure. Most importantly, we believe in the potential of our Allocarti products and have treated now more than 130 patients with lymphoma, multiple myeloma, and renal cell carcinoma across five Phase I studies. In the Alpha-1 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 presentation. 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 ALO501 and ALO501A continue to validate our consolidation strategy. ASH will feature an oral presentation on our Phase I Alpha-2 trial with ALO501A and a poster presentation on an alpha study with ALO501. Consistent with the data presented at ASCO earlier this year, the updates in the ASH abstract continue to support a favorable clinical profile for AllocardZ 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. We chose 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 re-administration of chemotherapy, allowing cells that persist from an initial dose to remain active while newly administered cells can work to consolidate a 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 Alpha-2 study at ASCO earlier this year included six evaluable large B-cell lymphoma patients treated with a single dose of allofibroin A and five evaluable large B-cell lymphoma patients from the consolidation cohort in this study. As of the ASHAFTRA data cutoff date in July, 15 patients had received allofibroin A, six in the single-dose cohort and nine in the consolidation cohort. with 12 patients, or six each, available for response at day 28. In the consolidation cohort, both the overall response rate and complete response rate were at 67%, with all three partial responses converting to CRs following consolidation. We look forward to presenting data on additional patients from the consolidation cohort 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 Allofil 501A continues to be manageable in both the single-dose and consolidation cohorts. Events of interest in the single-dose cohort were previously reported at the 2021 ASCO Annual Meeting. In the consolidation cohort, there was no cytokine release syndrome, no graft-versus-host disease, no IGAMS, no dose-limiting toxicity, no dose reductions or grade 3 plus infections, and infusion reactions were a grade 2. Among all treated patients, hadopenias were the most common adverse event that occurred in 72% of patients. The patient with aplastic anemia and the chromosomal abnormality treated in the Alpha-2 trial was not referenced in the ASHA abstract due to the timing of the data cutoff. Meanwhile, we continue to prepare for the advancement of the Allo5018 program into a pivotal phase to study. with the understanding that certain work streams are being delayed by the whole and subject to ongoing discussions with the FDA. In the ash abstract for the poster presentation of the Allo501-alpha trial, the updated data continues to highlight that allogeneic cardiac 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 histologies. In data presented across 36 CAR-T naive patients, response rates continue to be similar to those seen in autologous CAR-T therapy trials, and the modified intent-to-treat 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 of therapy of five days. As of the July ASH abstract data cutoff, five additional patients were treated relative to the data previously reported at ASCO earlier this year. Overall response rate and CR rates remain at 75% and 50%, respectively. In the 13 CAR-T naive patients with large visa 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%. Four of the seven follicular lymphoma patients enrolled in the consolidation cohort were evaluable for assessment after consolidation dosing at the time of the data cutoff with an overall response rate and CR rate of 100% and 75% respectively. As with Alpha-2, we will report on additional patients treated in the consolidation cohort of Alpha at the ASH meeting, with a few not able to receive a second dose following the clinical hall. The percent of patients remaining in CR at six months following a single infusion of Allo501 was 36% in large vessel lymphoma, which is similar to six-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 six-month CR rate in follicular lymphoma was 28%. There were no cases of GVHD or DLTs observed. As noted previously, one case of Grade 3 ICANNs was reported. Grade 1-2 CRS occurred in 22% of patients with one case of Grade 3 CRS. All were managed with standard protocol. Cytopenias were the most common adverse events and occurred in 83% of patients. Infection rates remained similar to those observed in autologous CAR-T trials. There were no new treatment emerging deaths reported in this abstract. The oral presentation I asked from our multiple myeloma program was focused on a single administration of allo715 at higher cell dose cohorts. Subject to the whole, we continue to target 2022 for data from the combination of allo715 with neurogastastat, consolidation dosing with allo715, and our allo605 turbo CAR study. Findings from universal abstract indicate that an allogeneic CAR-T cell therapy can be delivered rapidly and without the need for bridging therapy to patients with refractory multiple myeloma with a single dose of therapy capable of inducing deep response. The ASH abstract contains data as of June, with 42 patients treated at escalating doses of allo715 and doses of allo647 ranging from 39 milligrams to 90 milligrams. As with the alpha trials, the median time from enrollment to lymphodepletion was five days. Patients were in advanced stage of disease with a median of five prior lines of therapy, and 43% of patients were pentarefractory. The trial did not permit bridging therapy. When the initial universal dataset 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 two-dose levels of 320 million and 480 million CAR positive cells. At the time of the abstract, 26 patients were treated at the highest two-cell dose levels along with fludarabine, cyclophosphamide, and allo647 lymphodepletion. The overall response rate was 62%, with a very good partial response or better, or VGPR+, rate of 38.5%. Medium follow-up for these patients was 7.4 months, with a medium duration of response of 8.3 months. Of the 10 patients with the best response of VGPR+, 8 were found to be MRD-negative. No GDHD was observed. The most common grade 3 plus adverse events included cytopenias. CRS was reported in 52% of patients, in all cases grades 1 and 2, except for one patient with grade 3. One patient with grade 2 CRS experienced grade 1 neurotoxicity that resolved. Grade 3 plus infections occurred in 13% of patients, including two previously reported grade 5 events. We are pleased that the data from Universal showed that multiple myeloma patients treated with Allo715 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 AllocardT 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.
spk08: Thank you, Rafael, and good afternoon. We ended the quarter in a strong financial position with $861.7 million in cash, cash equivalents, and investments. In the third quarter of 2021, our research and development expenses were $58.7 million, which includes $10.1 million of non-cash stock-based compensation expense. General and administrative expenses were $19 million for the third quarter of 2021. which includes $10.8 million in non-cash stock-based compensation expense. Our net loss for the third quarter of 2021 was $78.2 million, or 57 cents per share, including non-cash stock-based compensation expense of $20.9 million. While the clinical hold has detracted from our ability to enroll patients into our five clinical studies, we continue to support multiple research and operational initiatives, including preparation for a potential pivotal Phase 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 and $330 million. This includes estimated non-cast 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.
spk21: Thank you. At this time, to ask a question, you will need to press star one on your telephone. Again, that is star one to ask a question. To withdraw your question, just press the pound key. Please stand by while we compile your Q&A roster. The first question comes from the line of Tyler Van Buren from Cowan. Your line is now open.
spk14: Hey, guys. Good afternoon. Thanks very much for taking the question. 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 ongoing internal investigation to generate the data that would make the FDA comfortable, whether that's testing samples from the manufacturing batch that produced the patient sample or other things that you might be doing.
spk02: Hi, Tyler. Good afternoon. This is Dave Chang. Let me take that question. In terms of whether we have received a communication related to the clinical hold, yes, we have received a clinical hold letter that details FDA's concerns as well as the data requirements. And also, we have met informally with FDA to discuss some of the details. So, you know, to that extent, we can talk about, but, you know, in terms of the details, other than what we have previously communicated, which is that, you know, the agency's concern around the single case of chromosomal abnormality is whether this has any clinical relevance. also whether there is any evidence of clonal expansion, and also whether there is a relation between the chromosomal abnormalities and gene editing. In each of these areas, our team has made tremendous progress in terms of making a path towards addressing each area of the concern. You know, that's about, you know, at this point, you know, what we are willing to share. And while the investigations are ongoing and, you know, this matter is still under FDA review, you know, we will not really, we cannot really talk too much into the details.
spk14: Thank you.
spk21: Your next question comes to the line of Michael Yee from Jefferies. Your line is now open.
spk16: Hi, this is Dennis on for my thanks for taking the questions. You outlined a few possible hypotheses on the last call regarding the chromosomal abnormality, whether it's from talents or just from T cell expansion. Has any of those changed given the additional work that you've done? And then number two, can you please lay out some of the timelines over the next few months in terms of your interactions with the FDA? How much back and forth do you expect? And, you know, just give investors a sense of the timelines on when this could be resolved. Thank you.
spk02: Yeah. In terms of FDA interaction, I would say that this is a very active and collaborative interaction. We have had, you know, sort of informal, you know, 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 hypotheses. Obviously, given all the published literature about the potential of gene editing nucleus to cause chromosomal structural deletions or abnormalities, we have to take that into a possibility. But we also highlighted that the kind of chromosomal abnormality that we have detected in this patient is also known to happen in healthy T cells as they go on the expansion. So those two plausible explanations still is the basis of our ongoing investigation.
spk21: Your next question comes to the line of Michael Schmidt from Guggenheim. Your line is now open.
spk15: Hey guys, I have two questions. Just another regulatory question. This one is around the end of phase one, you know, 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 get the go-ahead for the phase two study, which you said I think is a parallel process, you know, side-by-side to the clinical heart investigation.
spk02: Yeah, Mike, Rafael has been leading the end of phase one discussions with FDA, and I'll ask him to respond to your question. Yeah, I mean, obviously our main focus has been to, you know, on the whole activities, and we obviously are fully dedicated to that, and as David said, you know, interacting productively with FDA. In spite of that, FDA has remained engaged with us on the phase two pivotal trial for 501 . 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. 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.
spk15: Okay, great. And then a question out of 715. I might have missed it, but I'm curious how much additional data you'll be able to share at ASH on the multi-myeloma study and whether that will or will not include patients that have received consolidation.
spk02: In multiple myeloma we will not include consolidation. That started later and that will report next year. We will share data with, you know, about a few additional patients or some more patients that have been accumulated since the cutoff that was in June. as well as longer follow-up, both in terms of responses, durability, and MRD type of data. Okay, thank you.
spk21: Your next question comes from the line of John Newman from Canaccord. Your line is now open.
spk20: Hi, guys. Thanks for taking the question. I also had a question about the pivotal study, the Phase II pivotal 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? Thank you.
spk02: Yeah, hi, 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 conversions from PR to CRs And we are, as is part of your question, dosing also patients that have stable disease as well. And so we look forward to updating that at ASH with, you know, additional patients and additional follow-up.
spk21: Okay, thank you. Your next question comes to the line of Luca Issi from RBC Capital. Your line is now open.
spk06: Oh, great. Thanks so much for taking my question. I'll try to not ask questions from the clinical hold. So maybe on the pivotal trial, can you just remind us why you believe that the pivotal trial can be single arm? It looks like GenMab has started a pivotal trial for CD3, CD20 by receiving antibody head-to-head versus dealer's choice chemotherapy in a similar setting. So wondering why that's not the right comp for us to think about it. And then maybe in competition, obviously we've seen the data from CRISPR a couple 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. Thanks so much.
spk02: 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 for end of phase one meeting, and in preparation of the pivotal phase two study, we don't wanna 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 what are we gonna approach as a single dose of consolidation, I know that is an outstanding question. and we've been sort of dodging the question. And we're not dodging because we don't have a position. We have a position, but I think it's a little bit ahead of the game for us to talk and communicate about the 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 LO CAR T program, we believe that can be done from a uncontrolled single-arm study.
spk08: And, Luke, on CRISPR and the competition, obviously it's really not our place to comment on other parties' data. You know, we welcome competition. We think competition makes the field stronger. Certainly there's plenty of unmet medical need to support multiple potential entrants in the allogeneic cell therapy space. Obviously our focus is just on continuing to execute, try and lead this field, and optimize our first-in-class products.
spk06: Got it.
spk21: Thanks so much. Your next question comes from the line of Solvein Richter from Goldman Sachs. Your line is now open.
spk01: Good afternoon. Thanks for taking my question. With regard to the investigation, I don't know if you can comment whether you've been able to rule anything out at this point. And then secondly, on the multiple myeloma data, are you hitting a plateau here in terms of dose response just, you know, with regard to dose level four versus dose level three? Any thoughts there would be helpful.
spk02: Yes, 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 the 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. 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 cells, particularly at the medium doses of allo647, we see slightly higher responses with 480, but the numbers are still very small to be able to tell. So, I think, you know, the overall answer is that we will probably stop at 480 and analyze the data and then make a final decision as to what the recommended phase two dose will be.
spk01: Thank you.
spk21: Your next question comes from the line of Jason Gerberry. from Bank of America. The line is open.
spk07: Hey, this is Perry on the line for Jason. Thanks for taking our question. I guess just an additional question on the kind of assuming resolution of the clinical holds. Do you anticipate any updates to, I guess, screening protocols for this type of, you know, chromosomal abnormality that could happen? A second question, you know, in terms of once you respond to 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 just want to better understand, you know, when the, you know, pivotal trial initiation could happen. could start following that, following response to the FDA.
spk02: Yeah, Perry, let me take the question. I mean, you know, the questions that you are asking are very important questions. And, you know, we are working hard to come to a resolution to the issues related to our clinical hold. I mean, some of the, you know, questions at this point we don't believe that we're gonna have to change what we do in the clinical setting that much. 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 gonna take, I mean, I don't wanna speak for the FDA. 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.
spk07: Thank you.
spk21: Your next question comes to the line of Corey Kazimov from J.P. Morgan. Your line is now open.
spk13: Hey, good afternoon, guys. Thanks for taking the questions, too, for me as well. So first one is, with your update today on the alpha study saying four of the seven patients in consolidation cohort who are valuable for response are all follicular lymphoma. I'm curious, in terms of not having a valuable 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? Thank you.
spk02: Yeah, let me take that question, Corey. So 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 fatty alpha 2. So there, you know, we've reported the conversion of 3PRs to CRs and, you know, 67% CR rate. And we will update those results at ASH. And then can you repeat the second question, please?
spk13: Yeah, in terms of having patients who respond well to single-dose treatment, kind of what you can learn from that, why some will be better with single versus the consolidation, is this a marketplace where you think eventually everyone just goes to get consolidation therapy?
spk02: Yeah, it is true that some patients may do well with single-dose. And, you know, 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 that delta that we're looking for in terms of being able to improve beyond what is seen with the autologous therapy. So, you know, once we make a decision, you know, every patient will be treated uniformly in the pivotal trial.
spk21: Thank you. Your next question comes from the line for Ju Brassad from William Blair. Your line is now open.
spk11: Thanks for the question. I want to get your thoughts on two separate topics. First, kind of piggyback on the last question on consolidation therapy. In universal trial or I'm sorry, in the GSI and turbo car therapies, are you thinking about consolidation therapy there or using GSI twice? And then 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 LF501A. Thanks.
spk02: Yeah, so the... GSI study has a period of time of administration of GSI, so it's not a single dose. And, you know, that study is ongoing. We are accruing, we were accruing up to the whole, and we will resume once the whole is listed, obviously. And then we hope to report next year on that experience. 605 had already started. That's the turbo car. 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 cells. And then your additional question.
spk11: I just wanted to get your thoughts on the TRANSFORM and ZUMA7 data and potential for CDNs and allo in second-line transplant-eligible patients.
spk02: Yeah, so, I mean, obviously, the therapies in the autologous setting are moving into earlier lines of therapies. This is not a surprise, and, you know, this is... obviously great for patients. I think those results were fantastic. And they will have an influence on how we end up developing 501A. You know, we will follow a pathway of starting with relapse refractory patients, but we have plans for full development of the product as, you know, time goes on. And clearly, you know, the data, you know, from Transform has been very encouraging for us to really move 501 as well into earlier lines of therapy when the time is gone. Let me just add by saying we and others, 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 turbo car. I mean, that is a novel technology. I mean, you know, what a single infusion of turbo car construct will do is our key question. So, you know, stay tuned. You know, great questions, but, you know, we will do this step-by-step matter.
spk21: Your next question comes to the line of Mark Breidenbach from Oppenheimer. Your line is now open.
spk05: Hey, good afternoon. Thanks for taking the question. This is kind of related to one of the previous questions, but I guess I'm wondering, before the clinical holds were imposed, if you were able to enroll enough patients in the universal neurogasostat combination cohort and the consolidation dosing cohort and even the IGNITE study to potentially arrive at some sort of answer in 2022, as to which prong of your multi-prong strategy is working best in myeloma, or if you really think you'll have to enroll additional patients from what you already have in these studies before you'll be able to make any sort of conclusion one way or the other. Thank you.
spk02: Mark, let me take the question. Obviously, clinical hold was a headwind for us. I mean, we had to stop the enrollment in the clinical studies. that will definitely impact, you know, some of the timelines that we have previously communicated. At this point, you know, we are not ready to really talk about, you know, the data flow. Much of what you're talking about, including the data from the IGNITE, our solid tumor study, the TURBOCOT study of LO605, as well as the combination, you know, with the GSI, They were all planned for 2022. We will make our best attempt to keep the same timeline, but as expected, I mean, the clinical hold is delaying the enrollment. Obviously, we cannot enroll any patients and the data generation timeline.
spk05: Okay, fair enough. Thank you.
spk21: Your next question comes from a line of friend, Benjamin. from JMP Security, Sir Lance Melvin.
spk18: Hey, good afternoon, guys. Thanks for taking the questions. David, I know that you mentioned that you didn't want to comment on how long the FDA may take, but could you maybe provide some bookends as to how long it might take for you guys to respond, you know, to the FDA? And I guess just, you know, 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.
spk02: Yeah, in terms of the first question, I know that, you know, that is central to, you know, in a lot of people's mind. You know, we will not provide any, you know, timeline on the resolution of the clinical hold. But, you know, be assured, I mean, you know, the team's working very productively for the 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 FTA take before they respond to the, when companies respond to the clinical hold letter, The PDUFA clock for there is 30 days. I mean, that is a window during which they will have to respond. You know, they will have to act in a based on response that the sponsor produces, provides to the clinical hold letter.
spk08: And, Ren, thanks for the question on our Allergy and Overland joint venture in China. Obviously, we'll apply any learnings from our interactions with the FDA and our investigation of the chromosomal abnormality to everything we do going forward. But with regard to specific and direct impact on China and timelines, no, I don't think there is any. That joint venture is proceeding quite well. Obviously, we're still in the phase of building out infrastructure, including a manufacturing facility, so we can use the time to continue to lay that groundwork and hopefully be ready to conduct tech transfer in the future at an appropriate time.
spk18: Great. Thanks for taking the questions.
spk21: Your next question comes from the line of Benjamin Burnett from Stifel. Your line is now open.
spk04: Yeah, good afternoon. 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?
spk02: 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, allo647 prior to the second dose if they meet some study criteria. If they progress after the first dose, then they don't go on . Great. Thank you.
spk21: Your next question comes from the line of from Truist Securities. Your line is now open.
spk10: Hi, guys. Thanks for taking my questions. I'm going to do two as well. Just to follow up on Ryan's question, what will you What do you plan on announcing in regarding to the ongoing process? I'm wondering what you'll announce when you formally submit a response to the FTS 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 LBCL, but maybe the folks at CRISPR waited a little bit too long. So as we think about rolling this out into other tumor types, what's your approach to really figure that out? Thanks.
spk08: Asika, it's Eric. Let me take the first question on our disclosure strategy. You know, we aren't intending to give a play-by-play of, you know, 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, you know, meaningful and relevant to report. So stay tuned.
spk02: And with respect to the, you know, 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. I think that really optimizes the cell expansion kinetics, as well as our ability to use only 647 for the second cell infusion.
spk10: Great. Thanks for taking my question, guys.
spk21: Your next question comes from the line of Dane Leon from Raymond James. Your line is now open.
spk19: Thank you for taking the questions, too, from me. Firstly, was the clone with the chromosomal abnormality found in the starting batch material ahead of infusion into the patient? And then the second question I'd like to ask is, Do you have any updated clarity in discussions around the design of a potential pivotal study for allo501A, whether that study would contain a control arm or it would be a single arm study? Thank you.
spk02: Okay, Dane, let me take the first question and I'll ask Rafael to respond to the second one. In terms of, you know, when the chromosomal abnormality 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 nucleus that we employ for the manufacturing of our CAR T cells. But equally possible is that this is more of a natural phenomenon that can occur at some frequency when T cells undergo expansion. So let me just stop there without going too much into the details of how much we know at this point. Yeah, 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 follow the same path, particularly given the fact that we're an off-the-shelf therapy with the advantages of lack of apheresis and the ability to treat every patient and the differentiation with the autologous products. So at this point, that is our expectation and our belief that this will be a single-arm trial.
spk21: Your next question comes from the line of Robert Burns from HC Wainwright. Your line is now open.
spk09: Hi, this is Mitchell on for Robert. Thank you for taking our questions. The first question is, can you comment on any change in development plans after the clinical hold is lifted? Would there be potentially a faster route to approval with the post CAR T setting that you anticipate pursuing?
spk02: Okay, so in terms of any changes in the critical 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 cardiac therapy.
spk09: Okay, great. Thank you. 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?
spk02: Yeah, I think it's, you know, hard to sort of, you know, speak to that ahead of the Congress. I mean, we want to reserve the ability to present this and keep the confidentiality until the timelines of the Congress. So, you know, apologies for dodging the question, but stay tuned. you'll see the answer. And Ash is only four weeks from now.
spk09: Great. Thank you very much.
spk21: Your next question comes to the line of Calpit Patel from B. Riley. Your line is now open.
spk17: Yes, hi. Good afternoon. Thanks for taking the question. Maybe a little more color on the planned phase two for LO501A. I guess if you were to implement both single and consolidation dosing into your protocol, would it just simply be designed as two separate cohorts? I'm just trying to understand, you know, if you may need a greater number of total patients or even a larger study than what was required if you were to add that extra cohort. Thanks for the question.
spk02: Yeah, as I said before, I mean, we Without going into the details of how we will design the trial, we plan to have a single regimen in the study. We don't plan to have a single dose. A consolidation dose will be a single regimen and a single ARB trial. That's as far as we can go with regards to study design.
spk21: Your last question comes from the line of David Dai from SMBC. Your line is now open.
spk03: Hey, guys. Thanks for taking my questions. My last question around the Allo 605, the TurboCard T. Could you share with us some of the type of cytokine armory you're using to further improve the cytotoxic activity of the cells? And also, could you remind us for your clinical trials Are you using consolidation therapy, and also are you also combining with GSK for the ALA-605?
spk02: Yes, so the cerebral car study, we're extremely excited about that, the potential of these cars to actually expand, increase exhaustion, and have greater anti-tumor activity and potentially perhaps be able to use fewer cells. These are cytokine signaling that are generally gamma chain cytokines that are tropic to T cells. We haven't gone into the details of the specifics, but you can imagine that these are the kinds of cytokines that one sees to recover homostasis after a lymphodepletion. 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. You know, we will know it when we have a little bit more data once we resume the trial. Thank you so much.
spk21: Thank you. That concludes our question and answer session. I would like to turn the conference back over to management for any additional comments.
spk02: 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 are the team to bring the first allogenic cardiac 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.
spk21: 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.
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