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spk16: Hello and thank you for standing by and welcome to Allogene's Therapeutics third quarter of 2022 conference call. After the speaker's presentation, there will be a question and answer session. To ask a question during that session, you will need to press star 1 1 on your phone. Please limit yourself to one question and please be aware that today's conference call is being recorded. I would now like to turn the call over to Christine Cassiano, Chief Communications Officer. Ms. Cassiano, Please go ahead.
spk20: Thank you, Operator, and welcome to our Q3 call. After market closed, we issued a business update and financial results press release for the third quarter of 2022. This press release and today's webcast are available on our website. We ask you to limit your questions to one per person as we will keep this call to an hour and do our best to get to as many as possible. Joining me today are Dr. David Cheng, President and Chief Executive Officer, Dr. Rafael Amado, Executive Vice President of Research and Development, 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 success and timing of our ongoing and planned clinical trials, data presentations, regulatory filings, future research and development efforts, manufacturing capability, and 2022 financial guidance, 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 earnings press release and latest SEC disclosure documents. You are cautioned not to place undue reliance on these forward-looking statements, and Alexine disclaims any obligation to update these statements. I'll now turn the call over to David.
spk07: Thank you, Christine, and good afternoon. I will start today's call focused on our most important milestone, the initiation of our Phase II trial with Allo501A for the treatment of relapsed or refractory large B-cell lymphoma. Advancing our off-the-shelf Allogeneic CD19 CAR-T product candidate to a Phase II trial brings us one step closer to making this potentially lifesaving therapy more readily available to the patients. It is a culmination of our singular focus over the last three years and signifies our leadership in the development of allocardia products. And in my view, an advancement for the entire field of cell therapy. As you might imagine, we were very pleased last month to share that we have initiated the industry's first potentially pivotal phase two trial for an allogeneic CAR-T product. Being the first comes with a special set of challenges, but it also comes with an enormous sense of accomplishment and responsibility. When we started our journey, we knew there would be a unique set of challenges that we would have to address. Ensuring the safety of Allokar Q products, especially with respect to the graft-versus-host disease, protecting Allokar Q cells from being prematurely rejected by the patient's immune system, demonstrating meaningful responses, and managing reliable manufacturing of allococci products. Our depth of understanding around each of these elements, combined with the breadth of our clinical programs and the translational knowledge we have generated puts us at the forefront of science. The journey of drug development is often a winding road. And as we proceed through this journey and work towards addressing the challenges, we are tasked with keeping our focus. We have been unwavering in our commitment to ourselves, patients, and investors to create and lead the next revolution in cancer treatment by delivering to patients the first allogeneic CAR-T products for blood cancers and cellulose tumors. And initiating this phase two trial places us one meaningful step close to that ultimate goal. To that end, we are very much looking forward to providing a clinical update on our CD19 Alpha studies and our BCMA universal trial and our R&D showcase in New York on November 29th. While our usual practice for such updates is to target medical conferences, we believe our R&D showcase will provide more time and flexibility to fully review the clinical findings of our lead programs and discuss them in the context of a restfully evolving landscape. Before I turn the call over to Rafael, I would like to make a few more comments related specifically to the importance of collaboration with like-minded individuals and institutions. Our success to date in advancing cell therapy can only be accomplished with a partnership and support of engaged patient-focused investigators, and clinical trial sites. Their dedication to patient care is to be commended, and their desire to bring about options for their patients is underscored by the launch of a first-of-its-kind effort we call CAR-T Together. Real-world access challenges have emerged since the commercial introduction of McCann's CAR-T five years ago. Chief among them, the supply bottleneck created by the complex, individualized manufacturing process inherent in the delivery of autologous CAR-T therapy. This pioneering initiative, conducted in collaboration with key opinion leaders from top oncology centers, is aimed at supporting the advancement of allogeneic CAR-T products to address bottlenecks through collaboration, education, and clinical trial enrollment. Inaugural members of this initiative include lead investigators from Moffitt Cancer Center, the Sarah Cannon Colorado Blood Cancer Institute, the Mayo Clinic, and City of Hope. These dedicated physicians and the many more who participate in clinical trials sponsored by Allogene and others are leading the vanguard of scientific innovation. On a personal note, I had the pleasure of working with many of the same KOLs as we traveled the role towards bringing otologous CAR T therapies to patients, and I'm honored that they have chosen to join us again on this next chapter. As we noted last quarter, we started AlloGEN with the goal of making CAR T readily available to all eligible patients. As we near the conclusion of our fourth year together, we believe we are well along the path to transforming CAR therapy from a complex, individualized procedure to an off-the-shelf, on-demand pharmaceutical product. My sincere thanks to all our employees, investors, collaborators, and patients who have joined us on this journey. I will now turn the call over to Rafael. Thank you, David. As David noted, our teams are very pleased to have initiated our potentially registrational alpha-2 trial. Activities are also underway to launch our companion EXTEND-SAFE-2 trial. The ALPHA-2 trial utilizing allo501A in patients with relapsed or retracted large piece of lymphoma will deploy a single dose of allo501A at 120 million CAR-positive cells with a lymphodepletion regimen comprised of fludarabine and cyclophosphamide plus allo647. This single-arm trial will enroll approximately 100 patients who have received at least two prior lines of therapy and have not received prior anti-C19 therapy. The primary endpoint of this trial is overall response rate, with a key secondary endpoint of duration of response. As we onboard clinical sites for alpha-2 in the U.S., we're also continuing our discussions with the European Medicines Agency to initiate the alpha-2 study at European clinical sites. The EXPAND trial, a separate potentially registrational trial, is intended to demonstrate the contribution of allo-647 to the standard fludarabine and cyclophosphamide lymphodepletion regimen. Patients will be randomized to receive the same single 120 million cell dose of allo-5-ONA as in the alpha-2 trial and either lymphodepletion with fludarabine and cyclophosphamide alone, control on, or the same lymphodepletion regimen of the alpha-2 trial The trial is expected to enroll approximately 70 patients with a primary endpoint of progression-free survival and the key secondary endpoints of overall response rate and duration of response. We are looking forward to sharing clinical data from our CIM-19 program at our R&D showcase at the end of the month. We are planning to share longer-term follow-up data from the ALSA and ALSA2 Phase 1 trials including our rationale for selecting the dose and schedule of Allo501A being deployed in phase two. We also expect to share outcomes from patients treated with our alloy manufacturing process. Our R&D showcase will also feature updated data from our BCMA program, the only such allogeneic cell therapy program to have established proof of concept. At the event, we plan to share longer-term data from a single-dose Allo715 in the treatment of patients with rehabs or refractory multiple myeloma. The Allo715 program is increasingly exciting as we recognize the growing unmet need for BCMA-directed cell therapy and the transformational opportunity that AllocardT may play in addressing the need for treatment in these advanced patients. We recognize that the myeloma market is dynamic and believe that multiple innovative approaches will be required to further advance patient care. This is exactly what has transpired for the past 20 years in myeloma. Nonetheless, the profile we are targeting with allo715 appears differentiated among the competition in having the potential to provide patients an immediate off-the-shelf option with one-time dosing. Based upon physician interest in this profile and the clinical outcomes that we have previously shared, we believe that allo-7-1-5 could play a very important role in the myeloma treatment paradigm. Over the next few days and weeks, we expect a lot of discussion around the potential for innovation in treating blood cancers. At Allogene, we believe we now have line of sight not just to potential innovation but to potential products. We look forward to continuing to execute on this mission and sharing an update with you on November 29th. I'll now turn the call over to Eric.
spk14: Thank you, Rafael, and good afternoon. As I begin my formal remarks, I'd like to focus on a brief update on activities outside of the United States, starting first in China. As many of you will recall, Allogene and Overland partnered a little less than two years ago to create Allogene-Overland BioPharm, This joint venture focused on the development, manufacturing, and commercialization of allocarty therapies targeting BCMA, CD70, FLT3, and VLL3 in Greater China, Taiwan, South Korea, and Singapore arose from a shared vision that cell therapy represented a revolutionary new technology. Developing allogeneic CAR T options was especially important as we knew that autologous therapies would face even greater hurdles to adoption in China. where the population was large, diverse, and geographically dispersed. Since inception in late 2020, much has been accomplished. Allogene Overland BioPharm has built many of the necessary components to succeed, including the assembly of a strong leadership team with highly skilled employees. Most recently, it launched a state-of-the-art large-scale manufacturing facility. Through this venture, we have had the honor of partnering not just with Overland, but also with CEO Dr. Shuyuan Yao and his team in Shanghai. It is this partnership that will allow us the opportunity to extend the reach of Allocartes into China, and we look forward to supporting Allogene Overland as they begin to manufacture Allocartes cells. Rightfully so, our focus today has been on CD19 and Allo501A, a program that we advanced with the support of Servier under our license and collaboration agreement. We'd obtained rights to ALA 501A and other CD19 candidates in the U.S. from Servier, while Servier had retained ex-U.S. rights. In September, Servier informed us that they would no longer seek to commercialize ALA 501A or other CD19 products outside of the United States. We are pleased to have obtained the right to opt into ex-U.S. rights, which we are carefully evaluating. U.S. commercial rights are unchanged. Moving to our third quarter financials, We ended the quarter with $637 million in cash, cash equivalents, and investments. Our Q3 2022 research and development expenses were $63.6 million, which includes $11 million of non-cash stock-based compensation expense. General and administrative expenses were $18.9 million for the third quarter of 2022. which includes $10.1 million of non-cash stock-based compensation expense. Our net loss for the third quarter of 2022 was $83.1 million or 58 cents per share, including non-cash stock-based compensation expense of $21.1 million. We are revising our 2022 guidance for spending down modestly. We now expect GAAP operating expenses to be slightly below the low end of our prior range of $360 million and $390 million. This includes estimated non-cash stock-based compensation expense of $90 million to $100 million and excludes any impact from potential business development activities. Cash burn for 2022 is now expected to be less than $250 million. With that, we will now open the call to your questions.
spk16: Thank you. As a reminder, to ask a question, you'll need to press star 1 1 on your telephone. We also ask that you please limit yourself to one question. Stand by as we compile the Q&A roster. One moment, please, for our first question. Our first question will come from Salveen Richter of Goldman Sachs. Your line is open.
spk17: Hi, everyone. This is Andrea. I'm for Salveen. Thanks for taking our question. David, maybe could you speak a little bit more on the process that will be necessary as you transition between your current manufacturing and the alloy manufacturing, and in particular, what your plans are for comparability studies? Thanks so much.
spk07: Okay, Andrea. This is David Chang. So, let me take on that question. I think what you are asking is in reference to what we have said that will be used in our pivotal study, the alloy process. You know, this is something that we took a lot of time to, you know, come to that, you know, decision, and that's based on a lot of data review. And alloy process, you know, has been used in a number of patients that we have treated across our clinical programs. So the next step, you know, which is all important question about is what are we doing with the alloy process? We are doing exactly what you're saying. trying to bring that manufacturing process to our own manufacturing facility at CF1. And that involves the steps that we are very familiar with, validating few equipments and deploying our manufacturing personnel from, you know, different process that we were using to alloy process. So we expect that to occur in a relatively short period of time.
spk16: Thank you. One moment, please, for our next question. Our next question will come from Michael Yee of Jefferies. Your line is open.
spk02: Hey, David and team. Thanks for the question. With regards to multiple myeloma update, can you help us set some expectations from the standpoint of the a bar out there, both from a CR rate standpoint and a PFS and overall response rates, which we can all look at just the tables and the labels and the concept that they were perhaps treating different types of patients versus what you will show. And what is the bar to say that this is a good drug and we should be going forward versus what we have out there? Thank you.
spk07: Mike, So, yes, 715 will be a part of R&D showcase, and we will provide update on the 715. And as we've been talking about, the big component of the 715 update is the longer-term follow-up on the patients that we essentially have reported the initial findings back in, you know, Ash 2021. So, you know, following those patients, you know, both from the durability as well as other sort of response parameters, they will be key. So the important question that you're asking about, you know, what is the bar? As we've been saying, you know, the multiple myeloma field is evolving pretty quickly. And this is also where the, you know, treatment paradigm has really changed significantly over the last, you know, couple of decades from limited treatment to something that is a combination as well as sequential. So what we are looking here is really differentiation from other treatment. You know, CAR-T currently, you know, two autologous product is approved, but we are coming as an allogeneic CAR-T product, and there are many benefits that we can talk about why the allogeneic therapy is needed. This is also a space where by specifics are being approved, but there are different attributes that we can emphasize about why allogeneic CAR-T off-the-shelf therapy is needed. So this is really something that we are in constant discussion with the investigators and others. But let me also emphasize, no matter how great the results are, the treatment has to be available to the patients in need. And that is one of the key differentiation. And with that, let me ask, you know, if I have to comment about You know some of the detailed questions response rate and all that now which always evolves with a small number of patients that That based on which we will be making decisions Yes, Michael. So I'm clearly You know the data that we presented and ash last year was pretty encouraging and he was you know approaching the numbers of one of the approved products already and with the ability to treat virtually every patient that came into the study. And that was very much valued by physicians, particularly the lack of need of giving bridging therapy, VGPR plus rates in the upwards of 45% range. At the time, the durability of response was over eight months, and now we will have at our end of the day another year of follow-up with additional few patients you know, treated at a, you know, given leap of depletion, which we are, you know, honing into. So, you know, the data is becoming pretty attractive for us in terms of, you know, being very close to Apollo's therapy. Clearly, Garvicti has numbers that are superior, but we have patients that really can't wait, that come into the study without breathing therapy within days of entry and we get repeatedly, you know, investigators telling us that this is something that they would definitely use and would like for us to move forward with clinical trials. So, you know, I think there is a space, as in any disease, for multiple products, and definitely for an allergenic cell therapy, there is definitely room for a product like this. And we will see the profile evolve with time from the time that we presented last in 2021.
spk16: Thank you. One moment, please, for our next question. Our next question will come from Tyler Van Buren of Cohen. Your line is open.
spk01: Hey, guys. Thanks very much for the update. I understand it's a trade secret, but is there anything more you can tell us with respect to what is unique about the actual alloy manufacturing process at a high level? And to be clear, when you provide the update on November 29th, will you stratify the CD19 and or BCMA data for patients who received alloy versus those who have not?
spk07: Yeah, so, Tyler, you are absolutely right. You know, things that are related to manufacturing, there are a lot of trade secrets that we will not be able to talk about. But in the R&D showcase, you know, we will give some insights into why we landed with the, you know, Outlook process as we're, you know, launching the Pivotal 2 study. So, stay tuned for the R&D showcase.
spk08: Thank you.
spk16: One moment, please, for our next question. The next question will come from Ashika Gunewadding, a tourist. Your line is open.
spk21: Hi, guys. Thanks for taking my question. Rafa, you just mentioned that in the universal update coming up, you indicated that there will be a few more patients. I was wondering if you could help us out and maybe indicate if that's like five more patients, 10 more patients, any sense would be helpful. And I guess related, since the October 18th 2021 data cut from the alpha two phase one data presented. Ash, did you enroll and dose more patients on the phase one portion of that study as well?
spk14: Thanks, guys. Let me take that one. It's Eric. You know, we're not going to get into exactly how many additional patients we've treated, but of course, at the conference, the showcase on the 29th, we'll give you a full and comprehensive update of where we are with the program. And certainly we look forward to your participation in that event. As we've talked about, you know, our focus for both of these programs has been on following up patients longer term that were treated, you know, now some months ago and getting a better sense of how they're performing over time. So I think that will be the focus with the Phase I program in particular. You know, we've really been eyeing towards starting with Phase II for CD19 as opposed to treating a lot more patients.
spk16: Thank you. One moment, please, for the next question. Our next question will come from Raju Prasad of William Blair. Your line is open.
spk19: Thanks for taking the question. I just want to get a sense of the EXPAND trial. So it sounds like it's a dose of LL501A with Flucide versus Flucide Plus 647 with PFS as the endpoint. So is it really just to show non-inferiority here between the two arms, or do you want to see increased expansion? I'm just kind of curious to know the measures that were going to be considered a success from that trial. Thanks.
spk07: Yeah, thanks for the question. This is Rafael. Yeah, you're right on the design. It's really to isolate the contribution of 647 both to safety and efficacy. And as such, everybody gets 501A at the same cell dose as the alpha-2 with the two lymphodepletion regimens. In terms of the design, we have abundant data with regards to dose response and ability to lymphodeplete from real data. This is not model data. showing a dose response and also correlations between concentrations of allo647 and outcomes, clinical outcomes, which obviously leads us to believe that allo647 is required and is one of the critical components of lymphodepletion. And without adequate lymphodepletion, there's poor expansion and clinical outcomes are suboptimal. Therefore, we have a lot of conviction that this is going to be a positive trial. The endpoint is actually a clinical endpoint. It will be a progression-free survival and the sample size will be 70 patients. So that gives you a sense of the fact that we are looking for a difference that is meaningful because we really believe that the addition of six or seven is going to be critical to achieve really meaningful outcomes.
spk16: One moment, please, for the next question. Our next question will come from Rennie Benjamin of JMP Securities. Your line is open.
spk13: Hey, good afternoon, guys. Thanks for taking the questions, and I look forward to November 29th. Can you talk a little bit, you know, it seems like in the registrational study you're going to be treating patients with greater than two lines of therapy. Can you just remind us what was the average lines of therapy in the earlier studies? And did you guys see any sort of worsening, bettering, or kind of equivalent ORR across different exposures to therapy? And just kind of related to that, were any of the patients, you know, post-Tech Bailey in any of the studies?
spk07: This is Rafael. Yeah, these patients were heavily pretreated. You know, most of them had received, you know, about three to four lines of therapies. We looked at a number of predictors. Lines of therapies was one of them, chromosomal abnormalities such as, you know, double head, triple head, and other parameters such as LDH, et cetera. You know, we actually saw efficacy that was, you know, relatively comparable across multiple parameters, certainly lines of therapy being stamped out as one of the parameters that would discriminate good responders versus poor responders. So, you know, in that regard, you know, the critical criteria is that they are refractory to two lines or more.
spk16: Thank you. One moment please for our next question. Our next question will come from Mark Breidenbach of Oppenheimer. Your line is open.
spk04: Hey, good afternoon, guys. So on the last earnings call, I seem to remember you were talking about exploring pivotal trial options in multiple myeloma by year end. I guess I'm wondering if that's still the case. And also, can you remind us if universal is excluding patients with myeloma any prior BCMA-directed therapies, including Blenrep and some of the BCMA-CD3-5 specifics or just the BCMA CAR-Ts? Thanks for taking my question.
spk14: This is Eric. Let me take the first part of that question, and then I'm going to turn it over to Raphael to answer your universal question. In terms of our communications around the BCMA program, I think we've been fairly consistent in saying that we'll be providing next steps for the program at year end, not guaranteeing what those next steps could be. And of course, that's something we intend to follow through on at our showcase on the 29th. So again, please join us at that event and you'll get our latest thinking on what's next for the BCMA program.
spk07: Yeah, with regards to BCMA-directed therapy, those were allowed in universal, not patients that had received cell therapy, but patients that had received antibody therapy. And, you know, in general, we saw no difference between those that had received it and those that hadn't, but, you know, the numbers are small.
spk16: Thank you. One moment, please, for the next question. The next question will come from John Newman of Kennecois Genuity. Your line is open.
spk09: Hi, guys. Thank you for taking my question. I'm just curious, regarding the alloy process, if you could talk a little bit about how you plan on incorporating that product manufactured at Self-Forge 1 after the process is approved for Self-Forge 1. into the pivotal phase two. And just curious as to how you're thinking about comparability there with the CDMO product that's being manufactured using the alloy process at the moment. Thanks.
spk07: Yeah, John. This is David. Let me take that question. You know, alloy process, obviously, that is the process that, you know, we have announced as the, you know, product, you know, that will support the pivotal study. In terms of some of the questions, which are going a lot into the technical details, let me just say that in terms of demonstrating the comparability, we have done that already as we were testing different processes you know, across different programs. So I do have confidence in our technical operations team about the key things that one has to do to demonstrate the analytic comparability. So those things we have, you know, experience with it, and we will apply the knowledge that we have as we have to show the analytic comparability. And we'll provide some additional details in the R&D showcase about why we chose the RLOAD process. And also I realized that we are talking about R&D showcase in a lot of our answers. And let me just talk a little bit about our decision to have the R&D showcase, which is something that we have thought very carefully. The ultimate driver for us to go with the showcase is When we think about the topics that we have to cover, you know, based on all the inputs from, you know, you, you know, our analysts as well as some of the investors, it's really, you know, trying to really recap the history of, you know, 501, 501 development and why we landed with the final study design as well as the dose and the lymphodepletion regimen. This is really a complex issue, and we felt that the best way to provide the clarity and not confuse the presentation was more in a setting that has a little more time and also provide other context. So I think this was really the key driver for us to opt as the R&D showcase to provide the important updates on both 3D19 and BCMA programs. So, you know, it's coming up. I mean, November 29th is only about less than about, you know, four weeks away. And, you know, stay tuned, really.
spk16: Thank you. One moment, please, for the next question. The next question will come from Michael Schmidt of Guggenheim Partners. Your line is open.
spk18: Hey, guys. Thanks for taking my question. You know, I thought it was interesting to see that you decided to move forward with a one-time dosing regimen for Alpha-2 after, you know, looking at consolidation, re-dosing. A lot of the other allotherapy companies are still looking at re-dosing. And, you know, I thought that was interesting. I was just wondering, you know, if that is that one-time dosing, you know, concept is something you think, you know, applies to other programs as well, for example, 715, or if that is something that's unique to CD19.
spk07: Yeah, Michael, very important question. You know, at the end, You know, the key driver for choosing the single dose is looking, you know, it's a really data-driven decision. I mean, we have investigated both consolidation as well as single dose. And when we compared the data, we felt the single dose is as good as consolidation and certainly comes with the clarity of what the treatment is as well as convenience of completing the treatment with a single dose. And when we sort of put all those things together, I mean, the conclusion that we draw came very clear, and it's the obvious way that we will move forward. The second question about is this something that we will do across all different programs, we will continue to make data-driven decisions, and we will investigate and make the right decision on the future programs.
spk16: Thank you. And one moment for the next question. Our next question will come from Luca. Is this RBC Capital Markets? Your line is open.
spk22: Oh, great. Thanks so much for taking my question. Maybe one on the randomized trial for C19. Can you just talk about why the FDA asked you to use PFS as primary endpoint and response rate as secondary endpoint and not the opposite? It feels to me that asking for statistical superiority in PFS adds some risk to the trial and also will make the trial much longer. But again, we'd love to hear your thoughts. Thanks so much.
spk07: Hello, this is Dave Chang. Great question. And I think this is more of a technical things, you know, response. So bear with me. In a single study, FDA always has used the response rate and duration of response. When it goes to a randomized study, and, you know, there certainly has been many randomized studies, the best way to power the study as well as look at the both components of overall response rate as well as duration of response is time-dependent endpoint of progression-free survival. So, you know, sorry that my response is somewhat technical, but this is the most efficient way to really look at the contribution of 647 to the standard full-size regimen, which is the primary objective of that randomized expense study. Thank you.
spk16: And one moment for the next question. Our next question will come from Jason Gerberry of Bank of America. Your line is open.
spk10: Hi, guys. Thanks for taking my question. I just wanted to clarify on that last question, just to be clear, David. Is there an explicit regulatory bar for this EXPAND study to support, you know, registrational, you know, moving forward? If you can just maybe get more specific on that point, that would be really helpful.
spk07: So, you know, Rafael, do you want to take that? Sure. I mean, it is a study that's powered for superiority on PFS, which in self-therapy, because it is really, you know, CRs that drive, you know, long-term responses, there's not a whole lot of difference between durability of response and PFS. The study is par for superiority, and the bar is set based on the sample size. There's also a question of safety as well, which is important, but there really isn't a set bar other than the one that is detectable by the sample size, which is relatively small, and you can imagine that You know, based on that, it is a reasonable difference that we're looking for.
spk16: Thank you. One moment please for our next question. The next question will come from . Your line is open.
spk11: Yeah. Hey, good afternoon. Thanks for taking the question. Maybe one for LO6205. Can you comment on how the enrollment's going for that trial? Has the interest been maybe ticking up given the manufacturing constraints of approved BCMA therapies? And then do you intend on providing any updates from this study at the R&D event?
spk14: CalPIT, hey, it's Eric. Thanks for that question. On 605, yes, you know, as you know, we're in a dose ranging study, a phase one dose escalation study, and that continues. We've talked about having the R&D showcase focus on the 715 products, so you won't be seeing any data from 605 toward the end of this year. And we'll update you on that program as it goes forward. As you can imagine, yes, there's a fair bit of investor interest, investigator interest as well, in all of our BCMA programs.
spk16: Thank you. One moment, please, for the next question. Our next question will come from David Dye of SMBC. Your line is open.
spk05: Hey, Grace. Thanks for taking my questions. I just want to clarify a question on the Alpha-2 Pfizer trial. Following on the question on the single-dose regimen, maybe could you talk some more about potential to redose the patient in the trial? And would that be putting to the essentially later in the trial that you actually could be a redosed patient? And if so, what would be the criteria for redosing?
spk07: Yeah. So, David, this is Dave Chang. The redosing question, you know, we frequently get. And, you know, when I sort of think about the development of otolascar T, you know, that's something that we investigated. But from the Phase II clinical trial perspective, you know, keep in mind the objective of the Phase II study is demonstrate the treatment effect of the single dose. And, you know, when somebody, you know, requires a redosing, you know, which usually will be the case when there's no benefit or somebody after, you know, having responded progresses. In those patients, when that happens, any patients who get redosed, you know, will be censored from the efficacy analysis. So, you know, going forward with a pivotal study Redosing is not, you know, part of the study plan, you know, as a, you know, regards to the primary objective of the study. But when there is an opportunity, we will definitely investigate the redosing as an exploratory analysis.
spk16: Thank you. One moment for the next question. Our next question will come from Jack Helen of Beard. Your line is open.
spk06: Thank you so much, and congratulations to the team on the progress this quarter. I wanted to touch on the Sevier relationship, and I was hoping you could provide an update as to where things sit there, when we might hear more news, and then as it relates to the Alpha 2 study, how quickly do you think you could get sites initiated in Europe, or would you do that prior to settling the Sevier relationship as well? Thank you so much.
spk07: Hey, Jack. Would you mind repeating the initial part of the question? There was a little bit of glitch. We didn't clearly hear the beginning part of your question.
spk06: Yeah, sorry about that. I was asking about the CIVIA relationship. I was hoping to understand when we may get an update as it relates to the European rights for CD19 and how quickly you could start to initiate studies in Europe as well.
spk14: Okay, thank you, Jack, for that question. Yes, on CIVIA, as you know, and as we disclosed back in September, they made a decision to no longer participate in the development of C-19, essentially allowing us to set the issues outside the U.S. should we choose. We have the option to take over the global rights to C-19. Right now, as you know, under our collaboration with Servier, we just have the United States rights. So that's an option that we're going to consider quite carefully. It does come, if we choose to, with some some extra costs. We would be paying for 100% of the program as opposed to our current rate, 60%. But certainly, you know, the potential to market the product globally is also an attractive opportunity. In terms of what we're doing right now with the CD19 Phase II study, we already planned through the collaboration with Servier to enroll patients in Europe. So our plan was always to conduct a global study that would provide for global registration should it prove positive.
spk16: Thank you. Thank you. One moment for the next question. Our next question will come from Brian Chang of JP Morgan. Your line is open.
spk15: Hey, David. It's Tim. Thanks for taking my question. Just on the alloy process, is the alloy process only deployed for CD19? If CD19 is alloy or is there an alloy equivalent also deployed in your BCMA program as well, would you be able to give us some color on how long alloy has been in place? Thank you.
spk08: Brian, this is David.
spk07: So I'll take the question about the alloy, which I think we're getting into a third or fourth time in this call. So alloy process is one of the processes that we've been testing across our programs, and it has definitely been used in more than 501 programs. So definitely being able to generate data from across the program is helping our decision making, and in the R&D showcase, you know, we will, you know, provide the, you know, sort of thought process as well as supporting data about how we came to the plan of using the alloy for the pivotal study.
spk16: Thank you. One moment please for the next question. The next question will come from Robert Burns of HC Wainwright. Your line is open.
spk12: Hi, guys. Thanks for taking my question. Just one for me, if I may. You know, I know you terminated the collaboration with Sprintworks to evaluate LL715 in combination with Neurogas. I was just curious if during the R&D Day update, we would gain greater clarity as to the reasoning and, you know, some of the pharmacodynamic and pharmacokinetic measures from that evaluation. Thank you.
spk14: Rob, this is Eric. Thanks for the question. You know, it's an important consideration that we were trying to answer whether or not a gamma secretase inhibitor added to the benefit of allo715 in our hands. And yes, as you know, we discontinued that arm of the study because we didn't see meaningful benefit from the addition of a gamma secretase inhibitor to 715. And we'll certainly try and make that data available to you in the future. I'm not sure that the R&D showcase is the right form to do so. Honestly, we already have a A lot of things that we want to talk about, and this trial arm is, again, not something we're going to be moving forward with in development going forward.
spk16: Thank you. And one moment for our next question. The next question will come from Dane Leon of Raymond James. Your line is open.
spk23: Hi. Thank you for taking questions. I look forward to the R&D showcase. Could you maybe just clarify what steps still need to happen internally to get the pivotal Alloy 501A studies up and going, both the study itself and then the EXPAND study as well? Just kind of blocking and tackling type stuff, what still needs to be done there? Thank you.
spk07: Okay, Dane, this is Dave Chang. So in terms of alloy process, what's needed? Everything is already done. We have products that are made in the alloy process that will be used as we involve patients into the pivotal study. So there is nothing that is under critical step in terms of involving patients to the pivotal study. Probably what's underlying your question is what would it take for us to bring the alloy process to our manufacturing facility? And this is a process in terms of, you know, qualifying machines as well as utilizing the cell manufacturing operators. These are the people who actually manufacture the cells at the CF1, start making the products using the alloy. So this is something that we are very familiar about in how to go about doing this, and the work is already ongoing. Thank you.
spk16: One moment, please, for our next question. Our next question will come from Ben Burnett of Stifel. Your line is open, sir.
spk03: Hey, thank you very much. I had a question on your multiple myeloma strategy. I guess, do you think there's any value or is there any interest in trying to elucidate the efficacy profile of 715 or even the TurboCar in BCMA-experienced patients, just in the event that autologous BCMA CAR-T ends up moving upstream?
spk08: I mean, this is Rafael. It certainly is an interesting question.
spk07: You know, we know that a lot of patients with progression after BCMA-directed therapy still are BCMA-positive, unlike patients you know, many patients in the C19 space, and whether another DCMA-directed therapy may be effective or not is definitely a question of clinical interest. Yeah, I think it's premature for us to really tackle that question with all of 605. We are, as Eric said, in dose escalation in DCMA-naive patients, but it's a question that we may consider in the future.
spk16: Thank you. That concludes our question and answer session. I would like to turn the conference back over to management for any additional comments.
spk07: Thank you. First of all, thanks for joining us today, and thank you very much for very insightful questions. And we look forward to seeing many of you in person, I hope, at our R&D showcase later this month. You may now disconnect.
spk16: 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. Have a pleasant day.
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