Allogene Therapeutics, Inc.

Thank you for standing by. Welcome to Allogene Therapeutics' fourth quarter 2025 conference call. After the speaker's presentation, there'll be a question and answer session. To ask a question during the session, you'll need to press star 1-1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1-1 again. Please be aware that today's conference call is being recorded. I would like to turn the call over to Christine Castellano, Chief Corporate Affairs and Brand Strategy Officer. Ms. Castellano, please go ahead.

Thank you, Operator, and welcome everyone to AllerGene's conference call. After the market closed, AllerGene issued a press release that provided a business update and financial results for the fourth quarter and year-end 2025. This press release and today's webcast are available on our website. Following our prepared remarks, we will host a Q&A session and will aim to keep the call to under an hour. I'm joined today by Dr. David Chang, President and Chief Executive Officer, Dr. Zachary Roberts, Executive Vice President of Research and Development and Chief Medical Officer, and Jeff Parker, 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 capabilities, the safety and efficacy of our product candidates, commercial market forecasts, and 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 press release and latest SEC disclosure documents. You are cautioned not to place undue reliance on these forward-looking statements, and Allogene disclaims any obligation to update these statements. I'll now turn the call over to David.

Thank you, Christine. As we close 2025 and enter what we expect to be a defining year for Allogene, the environment around us is shifting. Cell therapy has entered a phase defined by evidence, where progress will be measured not by speculation and promises, but by data and disciplined execution. That shift plays to our strength. Our focus in 2026 is straightforward, delivering meaningful clinical milestones with rigor and speed. This is a year of critical proof points proof points that could validate our allogeneic platform, not merely as an alternative, but as the imperative path to making cell therapy scalable, accessible, and deliverable at biologic-like scale. First, with semicell and alpha-3, we are asking a bold but important question that could redefine the management of large B-cell lymphoma. Can we intervene earlier making CAR-Q truly accessible in the community setting, meaningfully improve outcomes, and alter the course of disease without disrupting the physician's practice. The goals of this study are not about incremental improvement in our late-line setting. It is about shifting the paradigm in the first-line treatment and demonstrating that semicell can reduce the risk of relapse and improve the kill rate. Importantly, it is about expanding access to community cancer centers that historically have been excluded from offering CAR-T, bringing advanced cell therapy to where most patients are treated off the shelf at biologic-like scale. Second, with Allo 3 to 9, we are extending the promise of allogeneic cell therapy to autoimmune disease. Allo329 is a purpose-built dual CD19-CD70 CAR design specifically for immune-mediated conditions, incorporating our Dagger technology to potentially reduce or maybe eliminate traditional lymphodepletion. We expect to report proof-of-concept data in June 2026, and assuming continued progress, another clinical update by the end of the year. We are entering this execution-focused period from a position of financial strength, having extended our runway into the first quarter of 2028. That gives us the ability to advance Alpha-3 and resolution with focus and discipline. We have built a broad and innovative clinical pipeline, but we recognize we cannot advance everything at once. Discipline requires prioritization. Today, we are concentrating our resources on the programs where allogeneic CAR T has the greatest potential to demonstrate what this modality can achieve when developed around its inherent advantages, scalability, accessibility, and ultimately, the potential for durable cure. At the same time, we believe that as the field recognizes that allogeneic CAR-T can deliver at scale with rigor and practicality, it will unlock new opportunities to expand the platform into additional settings and indications. With that, I will turn it over to Zach to walk through the clinical progress in more detail. Thanks, David.

As David outlined, the second quarter is defined by two key programs, semicell and alpha-3 and allo-329 in resolution. I'll concentrate on the clinical execution behind these studies and what we expect to learn in the months ahead, beginning with alpha-3. Alpha-3 is the first randomized study in lymphoma designed to test whether early MRD-guided consolidation with an allogeneic CAR-T can prevent relapse. Patients who achieve remission after standard first-line therapy undergo highly sensitive ctDNA testing. Those who are MRD positive and therefore at high risk of relapse are randomized to observation or treatment with semicell. In April, we plan to report results from the interim futility analysis evaluating MRD clearance in 24 patients, 12 each in the semicell treated arm and the control observation arm, along with early safety data. We will also outline the anticipated timeline and key inflection points as the study progresses. We've anchored expectations around what we and many clinicians believed would be a meaningful threshold at 25 to 30% absolute delta in MRD clearance between arms. Achieving that outcome would have the potential to alter disease trajectory and meaningfully improve the rate of cure of large B-cell lymphoma in the first-line setting. At the upcoming analysis, we also intend to provide preliminary safety data and additional perspective on how the use of semicell is being implemented in community settings. We now have over 60 active sites across the U.S. and Canada with engagement with health authorities and clinical site startup activities underway in Australia and South Korea. The level of real-world integration of Semicel as consolidation into routine practice across both academic and community centers underscores what we believe is a core advantage of the off-the-shelf model and its potential to expand access beyond traditional CAR-T delivery hubs. I'll now spend a few minutes on Allo329, our first-in-class dual CD19-CD70 allogeneic CAR-T therapy designed specifically for autoimmune disease. Allo329 was engineered for this setting from the outset. It targets CD19-positive B cells and CD70-positive activated T cells, both of which contribute to autoimmune disease. Our dagger technology is designed to endow the cells with a kind of built-in lymphodepletion to enable optimal cell expansion and persistence while potentially reducing or eliminating the need for conventional cytotoxic lymphodepletion. The phase 1 resolution trial is a 3 plus 3 dose escalation study enrolling patients across multiple rheumatology indications including systemic lupus erythematosus, lupus nephritis, scleroderma, and inflammatory myositis. The study is evaluating several dose levels beginning at 20 million CAR T-cells in two parallel dose escalation cohorts, one that includes cyclophosphamide only and one without any traditional lymphodepletion. 20 million cells is a small number, but one that we selected based on our conviction that the Dagger technology in Allo329 could drive meaningful in vivo expansion. For context, competitive programs in autoimmune disease are evaluating doses of autologous CAR T-cells that are up to 5 to 10 times higher than our starting dose, and other allogeneic cell therapy programs are exploring cell doses nearly 50 times higher. In June of this year, we expect to report initial proof of concept translational data as well as early clinical signals from the first dosing cohort with and without lymphodipletion. As an off-the-shelf allogeneic CAR-T product that does not require any degree of patient HLA matching, Allo329 persistence in patients treated with minimal or no lymphodepletion at this low starting cell dose would be a strong validation of the dagger effect in autoimmune patients. Assuming continued enrollment and follow-up, we anticipate providing an additional clinical update later this year. The opportunity in autoimmune disease could be significant, but success in this space requires tolerability, outpatient feasibility, and scalability, particularly as treatment moves into rheumatology practices. Allo 329 was engineered with those requirements in mind. Across both programs, our focus remains on disciplined execution with the goal of generating data that clearly define the role of allogeneic CAR T in early-aligned oncology and in autoimmune disease. With that, I'll turn the call over to Jeff.

Thank you, Zach. As we prepare for multiple clinical catalysts in 2026, our financial position is aligned with our strategic priorities. We have been deliberate in concentrating our resources behind Alpha 3 and resolution while maintaining balance sheet strength and operational flexibility. As of December 31st, 2025, we had $258.3 million in cash, cash equivalents, and investments. In February of this year, we received an additional $23.7 million previously held in escrow related to Servier's favorable arbitration outcome with Selectus. We have also made prudent and opportunistic use of our ATM equity facility and have raised an additional $20.7 million year to date. As a result of these actions, we have extended our cash runway into the first quarter of 2028, which we believe covers the timeframe we currently estimate is needed to complete enrollment in the Alpha 3 trial. R&D expenses for the fourth quarter were $28.6 million, including $2.5 million of non-cash stock-based compensation. For the full year of 2025, research and development expenses were $150.2 million, which includes $12.9 million of non-cash stock-based compensation expense. G&A expenses for Q4 2025 were $13.8 million, including $5.6 million in non-cash stock-based compensation. For the full year 2025, G&A expenses were $56.8 million, which includes $24.7 million of non-cash stock-based compensation expense. Net loss for the fourth quarter was $38.8 million, or 17 cents per share, including non-cash stock-based compensation expense of $8.1 million. For the full year of 2025, net loss was $190.9 million, or 87 cents per share, including non-cash stock-based compensation expense of $37.6 million and non-cash impairment of long-lived asset expense of $2.4 million. Guidance for operating cash expense in 2026 is expected to be approximately $150 million. GAAP operating expenses are expected to be approximately $210 million, including estimated non-cash stock-based compensation expense of approximately $35 million. These estimates exclude any impact from potential business development activities. With pivotal data from Alpha 3 approaching in April, proof of concept data for Allo 329 expected in June, and cash runway now extended into 2028, We believe we are well capitalized to execute through these important inflection points. Our focus remains clear. Advance high-impact programs, manage capital responsibly, and position AllerGene for long-term value creation. We'll now open the call for questions.

Thank you, ladies and gentlemen. If you have a question or a comment at this time, please press star 11 on your telephone. If your question has been answered, you wish to move yourself from the queue, please press star 11 again. We will pause for a moment while we compile our Q&A roster. Our first question comes from Tyler Van Buren with TD Cowan. Your line is open.

Hey, guys. Thanks for taking the question and looking forward to both data updates next quarter. Can you elaborate on the safety parameters you'll be looking at with the Alpha 3 data update next month and what the bar is to support broad uptake in the community setting? And perhaps more importantly, how investigators in the community setting have already responded to incorporating SemaCell as a seventh cycle of treatment in the frontline?

Thank you very much. I'll ask our CMO, Zach, to elaborate on safety aspects.

Hey, Tyler, thanks for the question. So we plan to provide some high-level safety information, enough for everybody to understand how well this is being tolerated. Unlikely it will go into very, very minute detail, but certainly serious adverse events in both arms, these sorts of adverse events that would lead to hospitalization, those sorts of things, which absolutely kind of feeds into your second and third questions. What is the bar that we need to hit for safety? We believe that this is best delivered as an outpatient. So therefore, this needs to be a therapy that can be delivered as an outpatient. It does not lead to rehospitalization due to adverse events. And finally, can this be done in the community? And absolutely, in the community, it's being done currently. And we look forward to sharing all of the safety aspects that are

allowing this to be taken up in the community by by physicians thank you one moment for our next question our next question comes from byron amin with piper sandler your line is open yeah hi guys thanks for taking my questions um i wanted to focus on the recent zuma 7 mrd analysis that were published last month where XSL observed a treatment difference of 20% on MRD negative, which, you know, translates to about an EFS benefit of around 27 months versus the control group. Given you're expecting a 25% to 30% difference on MRD conversion, what read-throughs do you have from the Zuma 7 data and your confidence on stopping at your interim EFS analysis? And on the interim EFS analysis, if you could maybe just walk us through how many events do you need and what assumptions on hazard ratio could lead to an early stoppage? And lastly, when can we expect interim EFS data? Thank you.

Hey, Barron. Thanks for pointing out on that recent MRD data analysis coming from subgroup patients who were involved in the Zuma 7 study. We view this study to be very consistent, you know, with how we've been, you know, looking at the MRD clearance and its correlation to the clinical outcome. You know, besides this study, you know, earlier study that we have been talking about is InVigor 11 study. where MRD clearance difference of 11% led to a very meaningful clinical difference. So what has been reported with Zuma 7 is very consistent, and I believe it sort of validates the guidance that we have been providing, which is 25 to 30% MRD clearance difference at the futility interim analysis that we project to share in April. So this is highly consistent and we do believe that 25 to 30% is gonna translate to very meaningful clinical difference in the outcome. So with respect to your second question, how much can we sort of speculate or model out about how the MRD clearance may translate to the EFS interim analysis? You know, I would say, you know, it just involves too many assumptions and speculations, and it's a little bit too early to talk about it. But internally, we're constantly, you know, reviewing the data and modifying our assumptions. So stay tuned. Great. Thank you.

One moment for our next question. Our next question comes from Michael Yee with UBS. Your line is open.

First, guys, we have two questions. One was your thinking. The first question is your thinking around the interim analysis and what would define whether you took that interim analysis on EFS. In other words, if the MRV conversion is super high, is that what would drive your thinking to take the EFS? So that is the question number one. And then question number two is on autoimmune. We wanted to understand the target product when you get your data coming up. Is this to be a low lymphodepletion, a no lymphodepletion type program? What are you trying to envision with the profile of that product? Thank you.

Yeah. You know, two great questions. In terms of, you know, this is, you know, somewhat similar to what Biren was trying to get, you know, I mean, One thing is that there isn't enough data out there to see how MRD clearance, the relationship between that and clinical outcomes such as event-free survival, whether this is a linear relationship, meaning that if there is a greater difference in the MRD clearance, there will be greater difference in the clinical outcome. That kind of data, while plausible, you know, there is such possibility of the data, so we can really establish the relationship other than saying, well, it is possible that, you know, if we see greater MRID clearance difference, that may translate to greater, you know, clinical benefit. And, you know, I get to the point about, you know, how that may sort of you know, put us in the time of interim EF analysis. I mean, interim EF analysis is, you know, is offer spending analysis. It is, you know, the primary endpoint analysis at a, you know, smaller event rate. And, you know, there is always possibility that interim analysis may cross the statistical boundary. I mean, that's why part of the reason that we do the interim analysis, not just us, everybody who does the interim analysis, but let's stay tuned. I mean, our focus right now is, you know, the MRD clearance, you know, that we promised to communicate in April of this year. And with the second question on the target product profile with the autoimmune program, our CD19, CD70, as Zach has covered in his prepared statement, this is highly differentiated program that is endowed with a dagger technology that may enable Allo329 to work at low or no lymphodepletion. So in the ongoing study, The baseline case that we are testing is load lymphodepletion, which is essentially using cyclophosphamide only. So standard lymphodepletion involves both cyclophosphamide and fludarabine. You know, we took out the fludarabine altogether and we lowered the cyclophosphamide dose to only one day infusion. So that is the baseline case that we are testing. And also we are testing as part of the study no lymphodepletion. So, you know, target product profile, you know, we are trying to get to is, you know, providing a meaningful B cell depletion that's leading to reset of the immune system at psychophosphate alone. I think that will be the base case. And obviously, if we can get to that without any lymphodepletion, there will be a great win. not just for the field but the patients and, you know, everything that people are trying to do with B-cell depletion in the autoimmune space.

Thank you. One moment for our next question. Our next question comes from Salveen Richter with Goldman Sachs. Your line is open.

Good afternoon. Thanks for taking my question. On the overall stem cell market opportunity and commercial positioning as CD3 bispecifics move to the front line, this could influence MRD positivity rates or directly exclude patients from stem cell eligibility. Just curious to get your thoughts on the evolving LBCL landscape and how you see stem cell positions long term. Thank you.

Hey, Salvine. This is Zach. Great question. It's been an interesting few years as these bispecifics have been approved in late lines and now are moving into frontline. I think if the early phase one data in untreated patients is consistent with the overall phase three readouts, there is a likely outcome that a certain percentage of patients may be cured with these very intense upfront regimens. So there is a possibility that there will be fewer MRD-positive patients. However, I think we very much need to wait for those final data before we begin to consider how the market opportunity may evolve, and not just efficacy but also safety and the pace at which these complex and expensive regimens are taken up in the community. Our initial feedback is that not everybody is going to be lining up to be giving these very, very complex regimens that often require hospitalization for step-up dosing and so forth. So we're watching this space very carefully, but we believe that the MRD positivity rate is largely going to be unchanged for the next many years.

Thank you. One moment for our next question. Our next question comes from Matt Phipps with William Blair. Your line is open.

Good afternoon. Thanks for taking my questions and the update on timeline staying on track. When you look at that foresight clarity data that looks at, you know, rates of MRD positivity post-RCHOP, are there any patterns around high-risk baseline characteristics such as double-hit, triple-hit genetics or you know, IPIs in the fours or something that, you know, you see in those patients that don't reach MRD clearance. And maybe you can remind us how Simicel performed in those types of subgroups in your previous relapsed refractory trial.

Thank you. Great question. This is Zach again.

So, absolutely, there does appear to be differential MRD positivity rates according to the baseline risk of patients, which is, of course, no surprise. The MRD positivity at the end of treatment is an extremely high risk for disease progression, and it is precisely disease progression that was used to generate those risk stratification tools. So it's very consistent that if you've got a high-risk disease at the time of diagnosis, you are more likely to be MRD positive at the end of frontline treatment, and of course then you're more likely to experience a relapse. The beauty of Alpha-3, however, though, is that there are lots of examples out there where patients who even have low-risk disease turn up to be MRD-positive at the end of treatment, and these are the patients that oncologists sort of keep oncologists up at night because you think that the patients are going to do very well, and then they end up experiencing a relapse. One of the things that we find so exciting about Alpha-3 is that everybody gets a shot at upfront cure, and we do the risk stratification at the end of treatment and then escalate care accordingly with a consolidation dose of Semacel. Looking back at our Phase I experience, we definitely saw good activity across the risk spectrum, so we do not anticipate there being gross disparities in the risk profile of these patients in the context of Alpha-3.

Thank you. One moment for our next question. Our next question comes from Samantha Semienko with Citi. Your line is open.

Hi, this is Ben on for Sam. Thanks so much for taking our question. Can you talk about expectations for the observation arm in the Alpha-3 study? What is the expected rate of spontaneous MRD conversion? And if there's any data, you could help us to triangulate this. Thank you.

Hey, Ben. This is Zach again. Great question. We get asked this one quite a lot. So we have long assumed that the number of patients who are clearing MRD without further treatment will be a non-zero number. We've modeled it about 20%. So in the 12-patient arm that we'll be revealing next month, We're talking about two to three patients that we expect to potentially have an MRD conversion from positive to negative. This comes back to the fact that no test in medicine is perfect. There are false positives and false negatives with every single test that you can perform, including PET scan. In fact, one of the reasons that MRD is so exciting and we believe will transform the care of these patients is because the false positive and false negative rates of the MRD test are significantly better than they are for PET scan. So this is why we are, you know, when we're talking about the efficacy that we hope to see in April next month is relative to the spontaneous clearance rate. So when we talk about 25 to 30%, we expect that improvement over the baseline clearance rate because patients, of course, are eligible to spontaneously clear in both arms. So we should expect that 20% distributed in both arms. As far as the data that we've used to model this goes, if you look at the publications around the test, the foresight test, there is a group of about 20 patients, 20% of patients or so, who are MRD positive at the end of frontline treatment who never go on to experience disease progression. So we've used that number to model the spontaneous clearance rate.

Thank you. One moment for our next question. Our next question comes from Matthew Begler with Opco. Your line is open.

Hey, guys. Wondering how you're thinking about label expansions here or if you'll need one to include other MRD assays. I know Adaptive has a test out there that's similar. And if so, what kind of validation work would that entail? Thanks.

Matt, Zach again here. So it's a really, really good question. And it's actually a very germane one because it's, you're absolutely right, adaptive has a test that's been on the market now for a few years. They're seeing rapid uptake across both academic and community centers. So we see this as strongly validating that MRD as a concept is going to become part of the standard of care. But they're not the only ones. Of course, Natera, who recently acquired Foresight, also has a test called Signatera that is used for lymphoma. So coming to your question, do we think that we will be restricted to use with Foresight? I think time will tell. I will say that in other areas of oncology where a diagnostic test has been required to determine eligibility for treatment, Very rapidly, there is a proliferation of people using different tests to determine eligibility for targeted therapy, for example, without necessarily requiring specific regulatory approval. So we are, of course, watching this very carefully, but we believe that there will be some ability to mix and match in a commercial context.

Thank you. One moment for our next question. Our next question comes from . Your line is open.

Hi, guys. Thanks for taking my question, and thanks for all the updates, too. Just a quick one for me. What proportion of the community centers that were treating patients on the Alpha-3 study had previously had AutoCard T and or transplant capabilities. I'm just trying to tease out, like, you know, as you roll this out into trial sites in the community, where if you had a substantial number of centers that is that first employee in the CAR-T rodeo with an allergenic product.

Hi, I asked Zach again. So I want to make sure I understand the question. Are you asking how many patients in the Alpha 3 study have previously been treated with transplants or AutoCard?

No, no, no. Yeah, yeah. We're looking specifically at the sites. I'm just wondering about, you know, site adaptation and how, if they didn't have any AutoCard T capabilities or transplant capabilities, if you were able to successfully bring them on board and have them set up for AutoCard T.

Got it, yes, okay, great question. So the study is open in about 60 sites now in North America. We've said it's roughly 50-50 community and academic. Of the community practices, a subset of those are CAR-T naive, so to speak. They've never given CAR-T. They don't have a transplant program. And those centers are actively enrolling and treating patients in Alpha-3. using Semacel as their very first CAR T that they've ever given to their patient. And I can say that it has gone very smoothly at those centers. And we are seeing very good uptake, very good tolerability with the product. And because this is, you know, can be done, bought at the bedside, administered in an infusion clinic, there isn't the need for the infrastructure or the dedicated team to manage autologous CAR T or transplant. So, we've been able to kind of swap right into how these clinics run their day-to-day infusions.

Thanks, Zach. I'm just wondering, are you able to comment on maybe what proportion of the community centers are these autocard T9 sites?

So I would say that I'm not going to be able to do that off the top of my head here. The sites that are listed on our clinicaltrials.gov, you know, they're all listed out there by sites. We'll provide a little bit more information on this, Ospica, at the time of the data update next month.

Great. Thanks, guys.

Thank you. One moment for our next question. Our next question comes from John Newman with Canaccord Genuity. Your line is open.

Hi, guys. Thanks for taking my question. Just had a question on L329 in the Resolution 1 trial. Just curious when you present top line data, if you plan to present any data on not just depletion of CD19 positive B cells, but depletion of the CD70 positive T cells. And also curious as to roughly what type of a time point after treatment you're looking at presenting data. Thanks.

Hey, John, let me give Zach a break and respond to your question. So, in an hour three to nine, the resolution study in autoimmune, you know, indication, you know, that study is progressing well. It is a dose escalation study, and as Zach had covered in the prepared remarks, we are studying at very conservative dose of 20 million cells just to safeguard the patients with a product that has never been tested in humans. The study is ongoing and at the time of the data analysis, many of the things and more, a lot of translational data, you know, we have plans, we are collecting the samples and we have plans to analyze. You know, probably at this point it's too premature to go into details of time points of sample collection. But the data communication, which will be primarily focused on dose level one, I mean, we believe that's about the time that we may come to treat all the dose level one patients. And translational aspect of what we are seeing with a 20 million dose will be the focus of the data communication.

Great. Thank you.

One moment for our next question. Our next question comes from Jack Allen with Bayard. Your line is open.

Hi, everyone. Thanks for taking my question. This is Chris on for Jack. Just going back to Alpha 3, I was just curious if you can provide some more color on just the overall pace of enrollment for the study, and then just a follow-up to that. I know you're limited on how much you can share on an ongoing trial, but can you share whether the percentage of patients showing MRD positivity following RCHOP is similar to your expectations heading into it. Thank you.

Hey, Chris. Zach again. So, you know, we don't give kind of month-to-month updates on the pace of enrollment. We have said that we expect to complete enrollment in the trial by the end of 2027, so that is very much on track. And with respect to your second question, is the rate of MRD positivity consistent with our assumptions, the answer is yes.

Thank you. One moment for our next question. Our next question comes from Brian Chang with JPMorgan. Your line is open.

Hi, guys. Thanks for taking our questions this afternoon. Just first, can you talk a little bit about the expectations for the top line? Will there be data to understand the trend of MRD clearance at several time points, Or will we only get one MRD rate at one defined time point? And if that is the case, can you remind me what time point would that be?

Hey, Brian.

Zach here. So, as we've been saying for a few months now, we've kind of outlined how frequently we're monitoring these patients for MRDs. So, we start checking at 45 days post-randomization, then again at 90 days, and then every three months thereafter. As far as the data that we will share next month, we will not be giving kind of longitudinal MRD status patient by patient. So we will be giving really top line information, how many patients cleared in the observation arm, how many patients cleared in the treatment arm.

Okay. And then just a follow-up. Can you talk about the variability then of MRD clearance? that you expect across, you know, a longitudinal period when you look at this interim first cut of 24 patients.

Do you mean how many patients may fluctuate around? Is that what you mean?

Yes. Yeah, just the variability based on the different time points. So let's say if you take a look at, the MRD rate at 25 days post-randomization versus, let's say, six months down the line, do you expect some spontaneous, you know, positive to negative or vice versa between those time periods? How do you think about the variability across these 24 patients?

Got it. Okay. So, the first thing that you need to keep in mind is that when patients have relapse with large B-cell lymphoma, it tends to happen pretty fast. The median time to disease progression from last dose of treatment is six months or less. And so MRD is highly predictive of relapse, highly prognostic test, very accurate. So we do not expect patients to spend a whole lot of time with very little MRD or MRD positive month after month after month. That's just generally not what happens in the majority of patients. Of course, coming back to a previous question, this idea of false positivity, there are going to be a few patients who have this low level of MRD positivity that never spontaneously clears and who can go for a long time before they relapse. So I think we're going to get a bit of a mixed bag, but for the most part, these patients have very, very high-risk disease, and we expect them to be MRD positive and likely to have disease progression relatively quickly after their last dose of treatment.

And Brian, let me just, you know, sort of comment, you know, additional comment. You know, our guidance on what would be a meaningful MRD clearance differential, you know, 25 to 30%, you know, also factors in, you know, if there was some kind of, you know, variability due to assay, sample collection. So, as I've said in the prepared remarks, we believe that, you know, the guidance that we have provided 25 to 30 is very conservative. and factors in many different elements in situations like this. And frankly, to Biren's question, the recent publication that again highlights a small difference in MRD clearance can translate to very meaningful difference in the clinical outcome. You know, I think that is very reassuring to us and really validates, you know, one of the key assumptions that went into providing that 25 to 30% guidance. Great.

Thank you. Thanks.

One moment for our next question. Our next question comes from Luca Essie with RBC. Your line is open.

Thanks so much for taking our questions. And congrats on all the progress and looking forward to data soon. We have a question on the statistical assumptions for CMSL. Can you talk about for the fatality analysis in a scenario where the delta versus observation is 10 to 15% versus the 20% to 25% that you're hoping to see, which is closer to Invigor 011 versus Zuma 7, would that prompt you to stop the trial? Again, I appreciate you're keeping some of these details close to your vest, but any comment on that is much appreciated. And maybe related to it, I think the trial is 220 patients, but you're looking at futility with just 24 patients. So what gives you the confidence that 24 patients is a large enough sample size? Thank you, Tim.

Yes, so there are many layers of question. Let me give Zach a break. This is Dave Chang. In terms of, you know, the futility aspect, I mean, you know, usually futility analysis gets done early on to see, you know, whether, you know, another hypothesis, you know, is in question, in which case, you know, study may be stopped for the lack of futility. I think we are a little bit past that point because earlier last year, you know, because of unrelated event, we had to do an unplanned analysis of MRD clearance with a very few patients. And, you know, from that data, which we have communicated where majority of patients were converting into MRD negativity. we, you know, essentially have cleared the futility bar. So, you know, we have made some remarks about, you know, in some ways this interim futility analysis is a misnomer because it's really, you know, trying to get early signs of what's going on with the MRD clearance. So that will be, you know, communicated. With respect to the statistical, you know, aspect of the study, you know, powering and all that, you know, those are the details that we haven't shared, and frankly, those are information that's better suited for when the study is complete and published, providing all the details. So we will continue to be a little bit coy about not providing any statistical powering of assumptions behind the study. But with respect to what the control arm versus the treatment arm we may see, when we say 25% to 30% is absolute delta we are talking about. So if the control arm has baseline MRD clearance or MRD positive patient going to MRD negativity for any reason at 15% to 20%, what we expect to see is in the treatment arm, that's 25 to 30% in addition to that 45 to 50%. So that's more or less what we have in sort of setting the bar for the futility analysis.

Thanks, David.

And I'm not showing any further questions at this time. I'd like to turn the call back over to management for any further remarks.

Well, thank you very much, and thank you for very pertinent and engaging questions. We said at the onset that cell therapy has entered a phase defined by evidence. That is where we attempt to compete through data and discipline execution and proof. The questions facing the field is no longer theoretical. I would say they are practical questions. Can these therapies be delivered broadly? Can they move earlier in the disease course? Can they extend beyond highly specialized cell therapy centers? and can they do so in a way that is sustainable? At AlloGene, those are the questions we have been building towards from the beginning. With Semacell, we are testing whether intervening at the point of molecular relapse can change the trajectory of disease. With Allo329, we are evaluating whether a purpose-built, dual-targeted Allogeneic CAR-T can open a new chapter in autoimmune disease. One, defined by scalability and accessibility. The coming year will not be about projections. It will be about proof. And with runway into the first quarter of 2028, we are positioned to execute with discipline and let the data guide what comes next. Thank you for your continuous support. Operator, you may now disconnect. Thank you.

Ladies and gentlemen, this concludes today's presentation. You may now disconnect and have a wonderful day.