Good afternoon, and thank you for joining our session of Citi's Virtual Oncology Leadership Summit. I'm Sam Semenkow, one of the senior biotech analysts here at Citi, and it's my pleasure to be hosting Allogene CMO, Zach Roberts. Zach, welcome, and thank you so much for joining us today. Thanks, Sam. Good to be here. And if those listening live, if you have any questions during the session, please feel free to email them to me at samantha.semenkow@citi.com. I'll be happy to ask them on your behalf, or send them through the portal if you're watching through Velocity. Okay. So, Zach, it's great to have you here. We are rapidly nearing the first data for the ALPHA3 study. This is a major milestone for Allogene. Maybe just to set the stage, could you just share a bit about cema-cel, give a little background there, the design of the ALPHA3 study, and a little bit about what data we're expecting in early 2Q? Sure. So cema-cel is an off-the-shelf allogeneic CAR T cell targeting CD19. It has been in the clinic for a number of years now. The first phase I study was run in the relapsed refractory large B-cell lymphoma setting, so these are patients who are third line. And we saw very good results in that phase I. We published in the Journal of Clinical Oncology last year, showing comparable efficacy to approved autologous products, as well as similar, if not, you know, numerically improved safety, including CRS and ICANS. In 2024, early 2024, we pivoted away from developing cema-cel in the third line relapse refractory lymphoma setting and moved it into this novel frontline consolidation trial that we call ALPHA3. ALPHA3 is the first of its kind in lymphoma, and it's unique for a number of reasons, but it's extremely well-tailored for an off-the-shelf, one-time treatment like, like cema-cel. So the, the gist of the trial is, patients who are newly diagnosed with large B-cell lymphoma, undergo standard frontline treatment. That's not part of the trial. This is just regular care that they receive with their oncologist, wherever that is, whether it's in the community or at an academic center, what have you. And the patients who achieve a remission to that frontline regimen, which is about 90% or so, will undergo, and this is part of the trial, will undergo an ultrasensitive minimal residual disease test that is based on a, a, a circulating tumor DNA, so it's a PCR-based test on, on blood. This test is far more sensitive than the CAT scan that the patient has received to demonstrate their remission. So if we find that these patients who are in remission have MRD in their blood, minimal residual disease, it means that there is residual tumor in these patients' bodies and that you just can't see on scan. So what ALPHA3 is doing is taking those patients who are MRD positive and therefore at a very high likelihood of having a relapse and randomizing them to the current standard of care, which is just close observation, watching and waiting, which is what you would do for these patients normally, waiting for their disease to come back, or whether you treat at that moment with cema-cel. So if you give a dose of cema-cel to those patients while they're in remission but remain MRD positive, can you improve their long-term outcomes? So that is the core premise of ALPHA3. And we, as I said, we think it's extremely well-suited to this platform because it's like a seventh cycle of treatment. You just give the patients an additional round of therapy if they need it. And we, as you pointed out, we're very excited because just around the corner in April, we're expecting our first look at data from this trial. And the specific data set that we will be examining and discussing publicly is whether or not we can eradicate or clear the minimal residual disease in these patients who receive cema-cel. We'll be looking at the rate of clearance from MRD positive to negative in both the observation arm as well as in the cema-cel arm, and that data will be shared publicly. Got it. Well, we're looking forward to that. So, can you share a little bit about how you're thinking about the bar for success in the futility analysis? I'm wondering, you know, what comps did you use to help frame this bar and any context into how you're thinking about how that should translate for the rest of the study. Yeah. So, I mean, the first thing to consider is that MRD status is highly prognostic. So if you're MRD positive, chances are your disease is gonna come back. If you're MRD negative, chances are very good that your disease is never going to come back. So, you know, accept that sort of as why this futility analysis looking at MRD is being conducted in the first place. Because we do believe that if you clear your MRD, that means, you know, good things are ahead. As far as what percentage of patients do we expect to clear their MRD in this upcoming analysis, we've settled on a 25 to 30% absolute difference between the two arms, and I call out the absolute difference intentionally because we do expect the MRD clearance in the observation arm to be non-zero. Historical data suggests that it's going to be around 20%. The number of patients in this analysis is 12 in each arm, 12 patients in the observation and 12 in the treatment arm. So, you know, one or two patients might clear their MRD spontaneously. That is fully expected. It doesn't mean that there's something wrong, but we expect those same 10 to 12%, or, sorry, 20%, one or two patients, to clear in both arms. So we want to see a delta on top of that when we add the cema-cel. So that, that is what it gives us this 25 to 30% improvement in MRD clearance. Why is that number important?... First of all, you have to appreciate that, you know, if you look at this as a frontline study, which I think reasonably you can, because these patients have not experienced a relapse. Outcomes there have been remarkably stable since rituximab was added to CHOP in the early 2000s. And only very recently did we see somebody actually beating R-CHOP, and that was the Polivy R-CHOP regimen in, from the POLARIX trial. And when you actually dig into the details of that approved regimen, there was really only a modest improvement in outcomes, about a 6.5% absolute improvement in PFS at 2 years over R-CHOP. What that translates to in sort of clinical practice is that you needed to treat 17 patients with Polivy R-CHOP to prevent 1 PFS event that you would have seen with R-CHOP alone. If you look at the second-line outcome, and specifically looking at auto CAR trials, Yescarta versus transplant, Breyanzi versus transplant in the ZUMA-7 and TRANSFORM studies. In those cases, there was about a 30% delta in the two arms, and those were both very, very positive trials. When I say delta, I mean in response rates and complete remission rates, and MRD is sort of a proxy for response rates. However, neither of those two examples incorporated MRD. So MRD use as an eligibility criteria for determining, you know, whether somebody should get treatment or not, this is a pretty new concept. ALPHA 3 is actually one of the very first trials to be doing it. However, we weren't the first, and there was actually a very interesting study that was just published a few months ago in the New England Journal. Highly analogous study design, but in muscle-invasive bladder cancer, so very, very high-risk bladder cancer patients. Like in ALPHA 3, they underwent definitive frontline treatment, were in remission after, in this case, surgery, but they underwent an MRD test, very similar to the test that we're using in ALPHA 3. And patients who were MRD positive were randomized to placebo versus additional treatment, in this case, with a checkpoint blocker. Even though that was a very, very positive trial, with respect to the primary endpoint, disease-free survival, as well as overall survival, so likely a practice-changing finding here. In a post-hoc analysis, they went back and looked at the MRD clearance rate in these patients, and in that context, they only found an 11% delta. So 14% of patients in the placebo arm cleared their MRD, as again, we expect some of our observation patients to clear MRD, and 25% of the patients in the treatment arm cleared their MRD. Even with that modest difference in MRD status, they saw a very, very positive trial outcome. So for all three of these data points, we think that 25 to 30% would be a very, very solid outcome for us at this upcoming analysis. Right. Okay, that makes a lot of sense. And you talked a little bit about the observation arm and the rate of spontaneous clearance. Do you know what drives that? Is it a false positive on the test, and then those patients were never positive to begin with? So there's probably a few reasons, Sam, that that can happen. You know, one of which is they are. The test is correctly identifying mutant DNA, which is what we're looking for, tumor-specific DNA in circulation. However, that residual disease was left over from a tumor that was already cleared, right? Because this is cell-free DNA. These are not viable tumor cells we're finding, we're just finding DNA fragments. So there could be, you know, a real detection of mutant DNA, but that tumor is all dead, so there's, you know, that's a false positive. Rarely, but it's non-zero, you can also be amplifying tumor that looks or, amplifying DNA that looks like tumor DNA, but it isn't. That is very, very uncommon, but it does happen with all tests. There's a few reasons why you can end up with a false positive rate, which we have to account for. Got it. Okay. And then what time points are you measuring MRD? I'm wondering if everyone will be from the same time point when you say they have or haven't cleared, or are we going to see a little bit of, you know, a trajectory of multiple time points and, you know, I guess, is it the most recent test that you're evaluating them on? So, how should we think about that going into the data? Yeah. So in order to avoid introducing a lot of bias, because obviously these patients are being enrolled kind of continuously, you know, we're looking at everybody at the same time. Okay. You know, we picked a day that we feel is a good time to look because, you know, there is some dynamism in the early days after cema-cel. But, you know, day 45 is when we're looking at the first time post-randomization, and it'll be that data that we share. Got it. Okay. That's helpful and clear. And then, you know, to your point about that, the bladder cancer study that had a very modest delta for the MRD clearance rate, it being around 11%, I guess I'm wondering: how do you think about what a true no-go scenario looks like if you were to get something that is below 25%, given the context that we have from that study and how it might transfer to the LBCL study? So, how, what would a no-go scenario look like versus, you know, some intermediate study where you don't make that 25% bar, but it's less? ... Yes, and it's kind of tough to pin that down because I think it's, it's gonna come, you know, a little bit of the eye of the beholder here, and I, I mean, the beholder can be Allogene, and, you know, we can look at this 11% from the IMvigor trial and say, "Oh, an 11% in ALPHA3, you know, may still yield a very positive outcome." But, you know, we're not the only stakeholders here, right? And investigators are gonna be looking at this data and trying to determine whether that is something that, you know, they want to put their patients on or whether they're gonna take their chances and potentially just give them salvage therapy. So, you know, I, I can't give you a number right now. It's probably something lower than 25 to 30%. But it would be surprising if we in the investigating community would tolerate 11%. But you know, you never know. And so I think we're really anchoring to this 25 to 30%. We think it's achievable, and we think it would be a, you know, if that translated to a 25 to 30% difference in EFS, that would be a practice-changing finding that would really revolutionize lymphoma care. Right. Okay, that makes sense. And to your point, I think at the beginning, you know, cema-cel has been shown to have a higher response rate in patients that had lower tumor burden, which is exactly the type of patient, maybe even more so, of what you're seeing in the ALPHA3. Is that accurate? That is. So in that phase 1 publication that we put out last year, we did a subgroup analysis and found that patients with low disease burden in that context, so these are not MRD patients, they're relapse refractory patients, but you obviously get a spectrum of disease burdens in a trial like that. You've got some patients with very, very bulky disease, and then you've got some with just a little bit. And when we went back and looked at outcomes based on the disease burden by two different measures, sort of how much we could measure by scan, as well as a blood marker that correlates with the disease burden, which is lactate dehydrogenase or LDH. In both cases, we saw significantly better efficacy than in patients who had very bulky tumors. And we weren't, of course, we weren't the first to find this. This has been shown now repeatedly in autologous CAR T as well, and in fact, that those observations have already begun to change practice with people doing things like trying to actively debulk tumors while the CAR T cells are being manufactured, so that by the time you give your Yescarta or Breyanzi or Kymriah, the patient is starting with far less tumor than they would have been had you not done that, because that both safety and efficacy outcomes tend to be better in those patients. So that, we've taken that obviously to the logical extreme with the ALPHA3 trial and are treating patients with the minimal detectable disease that we can, that you can imagine. Right. Right. Exactly. So we did have an investor question come through. They're asking: "Will you be providing any guidance on the safety profile during the futility analysis? We do expect to provide some safety. It's likely not going to be exhaustive, but in order to kind of be balanced about efficacy and safety. And we know I mean, we've, we've said for a long time that in this particular context, safety is a very important thing because these patients are in remission, so you don't want to be hospitalizing the patients for toxicity. You want this to be convenient. So, you know, if you can manage this being done as an outpatient, as, as we're doing in ALPHA3, that's even better. So, you know, we'll share some additional color on safety as well as likely where the patients in the trial are coming from. Are they coming from academic centers? Are Are they coming from community centers, et cetera? Got it. Okay. This investor is also asking about how you're thinking about the penetration of MRD testing in this setting. Are the majority of patients being treated in the community and any commentary on community doc experiences that you're able to share now, or if you'll be able to share it at the time of the readout? Yeah, we'll share some detail there. I can speak at a high level now, though. I mean, we've got about 50% or so of our clinical trial sites that are on ct.gov could be characterized as community practices. Some of those have never given CAR T before, so they've opted out of autologous CAR T products. They just don't offer them to their patients. These are patients who would otherwise need to be referred. So we do have several sites, large network practices, who are treating patients with CAR T for the first time. So, you know, in terms of the patient distributions and testing, it's about even. And then... Sorry, remind me the other two questions, Sam. Yes, he was saying. Oh, penetration. Any experiences that you could share and, yeah, penetration of MRD testing. Yeah. So we're at the cutting edge here of MRD. I will say that the field is moving very quickly, and so we picked a diagnostic partner at the start of ALPHA3, based on the strength of their data. That was a private company, Foresight Diagnostics, you know, that had spun out of Stanford. And you know, that was their data that really sort of sparked the ALPHA3 design. That company has since been acquired by Natera as of December of last year, and so there is an aggressive sort of push to get MRD testing into the lymphoma space. I think it's beyond question at this point that the momentum is building extremely quickly, and we see established MRD tests like clonoSEQ by Adaptive Biotechnologies being undergoing rapid growth in the lymphoma practices across the country. The reality is this test is just a better test than PET-CT, which is what we've been using for decades. It gives better information to the patients and the doctors about what to expect from their disease. It's easier to do, right? You're not exposing the patient to radiation and booking scanner time. And so, you know, we think that this is going to revolutionize disease assessment. So penetration, admittedly, is on the low side now, but it's going to be growing very, very quickly, just because it's an easier, better tool to provide information on prognosis. ... Got it. That's super helpful. And then maybe let's take a step back, sort of building on this, and can you just walk us through the patient journey, from diagnosis to dosing with cema-cel, and I guess how you think about that translating into, you know, real-world utilization as well? Yeah. So, one of the beauties of ALPHA3 is that we are silent on those upfront decisions that are made by the clinician that are targeted to that individual patient in front of them. So, you know, patients who are diagnosed with large B-cell lymphoma come in all shapes and sizes, from very, very sick patients who end up in an emergency room somewhere and are diagnosed and treated with their first cycle in the hospital 'cause they're so sick, versus patients who are diagnosed, you know, with relatively slow-growing disease, low burden in the outpatient context. Those clinicians and patients can make decisions to treat those patients completely without thinking about ALPHA3 or MRD testing. You pick a regimen that suits the patient in that moment. About two-thirds of these patients, generally speaking, across the board, will be cured with that frontline therapy. One of the reasons why MRD testing is going to grow rapidly in this space is if you're MRD negative at the end of treatment, you are about 90% sure that you're never going to experience a relapse. So this is highly valuable information for these patients. And indeed, in the context of ALPHA3, about four out of five patients that we test are MRD negative, and that's great news. It's great news for the doctor, it's great news for the patient. About one in five that we're testing are coming back positive. So in this context then, if you complete frontline treatment, you get your MRD test, and you're found to be positive, then you are screened for ALPHA3, very straightforward eligibility criteria, and then if you test in and agree to participate, then you are randomized to either close observation, which is what you would currently get. There's no treatment decision right now that's approved, that's based on MRD status alone, or you are randomized to the cema-cel treatment. The cema-cel treatment comes with a standard lymphodepletion or conditioning regimen that's comprised of fludarabine and Cytoxan, the standard regimen that is given for CAR T cells in other contexts, and then a single infusion of cema-cel. It is entirely up to the patient and the doctor to do this inpatient or outpatient. Majority of patients are being managed fully as outpatients. Both the lymphodepletion as well as the cema-cel infusion can be done in infusion clinics, and the patient is sent home. And then in both cases, observation or cema-cel treatment, then you enter routine follow-up to assess for safety outcomes as well as disease recurrence. Got it. Okay. And then, you know, how has enrollment been progressing? I think, you know, maybe this time last year, you had implemented a few changes in how you went about screening. I'm wondering, you know, are you seeing any remaining bottlenecks across your sites, or have you largely worked through those challenges that you'd previously identified? We've largely worked through them. And, you know, just to kind of provide a little bit more background on that, you're absolutely correct. It was just about a year ago now that we made an adjustment to the expected completion of enrollment timeline based on a slower than expected start to enrollment. And there's quite a few reasons, and I won't belabor them all here, but they can all be summarized in a nutshell, which is the patients that were being screened for MRD and consented for the MRD test itself, which is the first step to get into ALPHA3. You know, these patients are just generally not thought of to be clinical trial patients in the first place, right? They're getting a standard regimen. They're doing well, right? By definition, they're in remission at the end. And so it was sort of an additional piece of the workflow to get the clinicians to think, "Oh, I should, I should, you know, address this very healthy patient in remission with a potential clinical trial option." It just took a little bit of training and muscle memory to be built up to do that. But once that was established, and we sort of crafted materials to help train doctors to inform patients on the value of the MRD testing, once that kind of took hold, it really changed the game, and now it's being done quite routinely for all potentially eligible patients in these practices. Again, we're agnostic on frontline regimen. As long as they're not on a, on a clinical trial or receiving some experimental regimen, any regimen is potentially eligible for ALPHA3. So these patients are being approached now routinely, and so we've taken these best practices and now are applying them to all the new sites that are onboarding. So we really have, as I said, largely solved some of those, some of those initial challenges that were just due to the fact that this was a very novel study design. Great, got it. That's great to hear. And do you think that, given that, that you'll have a bit of a better sense of when you might have some of that final EFS readout timing, and is that something we could hear about during the futility analysis readout? Yeah. So we do expect to provide a little more detail on the timeline for the upcoming efficacy analyses, and it's not just the primary. We actually have an interim EFS analysis as well. That's not the futility analysis that we're talking about for this coming April, but it'll occur later, and we'll provide more detail on that when we share the interim futility data. We are saying, however, that, you know, we are on track to complete enrollment by the end of next year, but because these patients with MRD-positive disease tend to progress very quickly, we expect that those events to come in fairly rapidly. So we expect relative near-term EFS data in both the interim analysis as well as the primary, but more details to come. Got it. That was going to be my next question. You know, how long does it generally take for an MRD positive patient to relapse in this setting? Yeah, so it can be very, very fast and, and, there's obviously a Kaplan-Meier curve associated with this, and about a third of the patients are going to progress within three months or so. Median time is about, you know, six months or less from their last dose of chemo. So this really is kind of an emergency if you think of it that way, and trying to prevent the relapses, which comes back to, again, what makes cema-cel such a uniquely well-positioned product to, to treat MRD disease because there's no waiting. You don't need to apheresis a patient, then wait for manufacturing. Many of those patients, if you were to try to do this with an autologous product, would end up progressing during manufacturing, which of course, is the whole premise of ALPHA3 is to prevent that relapse. Similarly, if you tried to do it with a bispecific or something else, you end up putting a patient on more chronic therapy, which, you know, from the day of their diagnosis, they've been told by probably multiple people that they have a curable malignancy, and if they achieve remission at the end of six cycles, they're good to go. And then, you know, you do this blood test, and then you say, "Okay, well, I've got another six or 12 months of treatment to give you." A lot of patients aren't going to be okay with that. Whereas with cema-cel, you know, you just, it's an off-the-shelf product. You give it to them, and it's one and done, and you move on, so it's a lot more attractive. Right. No, definitely. And then, you know, in the prior question response, you mentioned the interim EFS analysis. Remind me, is that something you plan to share with the street, or would that be more of an internal check? So I think stand by for more detail on that one, Sam. Obviously, I think, you know, as we get closer to that and a lot can change between now and then, you know, so I think probably better for me to defer answering that question directly until we've got the interim futility analysis in just a few weeks. Got it. Okay, TBD. And then, you know, just sticking with the EFS theme, can you just speak to, I guess, how predictive MRD negative is to, maintaining EFS? And, just share a little bit more about how you're thinking about that 25 to 30% will actually or MRD clearance rate will actually translate into that stat sig. Is that... I mean, based on the Kaplan-Meier curves we've seen, based on MRD status, it seems pretty clear. Is that what we should be looking at and how we're thinking about probability of success if you achieve this? I think that's very fair, Sam. The whole value proposition of this MRD test is that it gives you good prognostic information and that, you know, the frontline MRD test is highly prognostic. That's in our corporate deck, but it's also been looked at in the second line post-CAR T. It's been looked at the third line post-CAR T, and no matter where you look, if you clear MRD from positive to negative, it tends to mean that you are cured, and now obviously, it's not 100%, of course, right? And some patients who do clear MRD end up, you know, having a relapse at some point in the future. I mean, no test is perfect, but by and large, it correlates highly with long-term disease outcomes. Yeah. No. Okay, that makes a lot of sense. And so then, you know, one of the questions I've gotten a few times actually over the last couple of weeks is: why wouldn't the MRD clearance rate for cema-cel be higher than that, you know, 25 to 30% delta? You know, if you're expecting 20% in the observation arm, give or take, you know, why wouldn't it be more than that, you know, 45 to 50% in the cema-cel arm? Yeah, look, to be very clear, we would love it to be more. Obviously, we would love it to be everybody, right? The whole point is we're trying to cure patients with ALPHA3, and the more patients that we can cure, the better. However, cancer is a formidable enemy, right? And these patients, some of these patients, unfortunately, are destined to die of lymphoma no matter what we Allogene, their doctor, anybody else does about it, right? I mean, even if you look at autologous CAR T in the second line, it's still better than even odds that if you get Yescarta or Breyanzi, that you will have a disease progression and will die of lymphoma. I mean, the long-term disease control in those trials was 40% or so. So some of these patients just have bad disease biology, and we have to account for that. Do we think that we have stacked the deck in favor of this intervention to eradicate that minimal disease? Of course, that's why we designed the study the way we did. Because the tumor is almost gone. It's just not quite. So we think that we've put these patients and, you know, cema-cel in a good position here, but we have to wait for the data and, you know, to come back and think, "All right, what does good look like here?" You know, it's not. It shouldn't be based on some hypothetical around, well, cema-cel should do better than this. We should really anchor to the clinical outcomes that are already there, and 25 to 30% improvement in cure in front line would be transformational. That would be something that has not happened since rituximab was added to CHOP. So that's, you know, something that we are anchoring to, we think would be really great. If it's 50%, you know, you'll hear me shouting from the rooftops. Yes, absolutely. And that's a good comp, I guess, to the rituximab piece. It's a good way to think about it. Okay, so let's say that it is a positive study, and I mean that, like, on the EFS primary endpoint, so down the road... How do you envision the commercial launch looking? Do you have some strategies in place for increasing MRD testing? I feel like you've already kind of done that from your trial sites. Is that something you can, you know, extrapolate out to a more broad setting, and how you're educating the sites, and how do you think about administering or convincing physicians to administer cema-cel to their patients? Yeah. So I mean, the short answer, Sam, is it's all going to depend on the data. Now, like your, the premise of your question is that we have a positive study, so let's work with that. The big question is how many, how plentiful will these MRD positive patients be? Now, the answer to that question is, we expect about 30% of patients who achieve a remission to be MRD positive. Maybe not all of them will be positive on the first test. So as I mentioned earlier, we're seeing about 20% MRD positivity. That is because there are some patients who actually are below the limit of detection on that first test at day 45, but at some point down the road, they end up above the limit of detection and are MRD positive but have not yet relapsed. We envision, as is already being done with the approved MRD test for lymphoma, that these patients will be tested serially after they complete frontline. In fact, some of these patients are being tested over the course of frontline as well, because that has been shown to be prognostic, too. If you have a big reduction in your MRD level during treatment, that tends to mean that you're on a better trajectory than if you don't. So these patients are going to be monitored serially. So we will be able to catch these patients at the MRD positive, yet still in remission stage across the board, so that will get us to that 30%. The launch of the various MRD tests is going to be important here, and, you know, we originally did get some questions around, "Well, you've picked this test that is being developed by a small private biotech that just, you know, is just sort of finding its footing. You know, is that the best thing to think about commercialization?" You know, at Allogene, we like to think of ourselves as very science-focused, and we follow the data where it is, and they had the best data as we were designing the ALPHA3 study. I think that commercial overhang for the launch has largely been taken off the table since Natera acquired Foresight in December. Obviously, Natera is a huge player, probably the world's dominant player in minimal residual disease testing. And, you know, we expect them to be quite aggressive in promoting MRD testing, and we think the data absolutely supports it. So by the time ALPHA3 is read out and is positive and, you know, is FDA approved, of course, you know, lots, lots of wood to chop between here and then, but the premise of your question is that's where we'll be. We expect MRD testing to be done pretty much for every patient, and as of now, we are still the only trial that is pegging a clinical decision on the result of the MRD test. So we may be the only therapy that's available to patients who are MRD positive, yet not yet experiencing clinical relapse. So we kind of have a wide-open path for a commercial launch here. At least that's how we see it at this, at this time. Got it. Okay, and I have another investor question here. They're asking about a doctor's willingness to use cema-cel ahead of autologous CAR T or bispecifics. And let me expand the question even further. How do you think about competition from CAR Ts that are in trials now for first-line large B-cell lymphoma? Two-parter. Yeah. So, I'll take the second one first. So, you know, there are... there's really only one trial that's open currently for patients who are newly diagnosed. That is a study that is focused on the highest-risk lymphoma patients. And these, when I say highest risk, I mean when a patient is newly diagnosed with DLBCL or other large B-cell lymphomas, there's a set of tools that we can use to risk stratify your likelihood of having bad disease versus curable disease. And the frontline studies with CAR T-cells or even other highly intense regimens like bispecifics are only focusing on the subgroup of patients who, at diagnosis, look to be high risk. Some of the issues with that concept is these while validated, these upfront risk stratification tools are notoriously imperfect, and a patient who looks to be very high risk at, on day one actually does extremely well with our job and is cured. And then the other end of the spectrum is also true, that you have a patient who, by these risk stratification tools, looks to be low risk, and they're the ones who have primary refractory disease and end up having a horrible outcome. So one of the great things about ALPHA3 is that we don't really pay attention to those upfront risk stratification tools. We let everybody, you know, get their risk stratification at the end using an actual test that is binary. You know, if you're positive, you're high risk. If you're negative, you're low risk. So we think that, you know, in terms of attractiveness to an everyday clinician, an ALPHA3-type approach is going to be more attractive than that sort of upfront, you know, giving somebody CAR T that may actually do just fine with a standard regimen. Of course, we are also being able to do this in the community, whereas, you know, in the context of autologous CAR T, that just isn't happening at any appreciable level. So 80% of patients with newly diagnosed lymphoma are treated in the community, and we, by our product design and attributes, we're able to target those patients, whereas, you know, that's not the case for autologous. And then remind me the other part of the question, Sam. Sorry. Just the willingness to use cema-cel ahead of autologous CAR T in the, I assume, in the relapse setting, or bispecifics. Yeah. So I think, you know, if I'm being totally honest, I think every clinician is going to have to make that determination on their own. I, you know, I think if you are practicing at a major academic institution, and you've got ready access to autologous products, and you're reasonably confident that if a patient progresses, you can rapidly administer safely with good efficacy outcomes, autologous CAR T, maybe, maybe you'll wait. I do think that that's an awful lot to ask of the patient. If you have conducted this MRD test, as I expect everyone will have an MRD test done eventually, and then it comes back positive, and, you know, you tell the patient, "Okay, well, we're just going to sit on this and wait for your disease to come back, and hope it doesn't come back in your brain or some other horrible situation that is going to make autologous CAR T a little tricky, versus giving you something that we can do right now as an outpatient, you know, and hopefully, that does the trick." So, you know, ultimately, it's going to come down to the data, and if that 25 to 30% holds and we have a positive EFS outcome in the end, I think it's going to be hard-pressed for clinicians to say, "I'm just going to wait to give Yescarta if this cema-cel data looks positive." It just it's, it's going to be an easier product to give and, you know, right in line with the frontline treatment. You know, it's just more amenable to sort of everyday practice and better for the patients in my view. Got it. Yeah, that makes a lot of sense. Okay, so then, you know, we only have a couple of minutes left. Maybe, Zach, you could just recap expectations for everyone ahead of the futility readout and any other closing remarks that you wanted to share. Yeah, I mean, I think all eyes are on this upcoming futility analysis. It's expected in April. And, you know, we—for all the reasons that we've discussed, Sam, we think it's going to be a really meaningful update. And even though we refer to it as a futility analysis, we actually think that this is going to be a highly derisking data set for the overall study. And the other thing that I just want to leave everybody with is, you know, Allogene set out seven or eight years ago with a vision to revolutionize the way CAR T is given, and originally, that was focused on the fact that this was off the shelf in allogeneic, and of course, that still applies. But what ALPHA3 really represents is an evolution in that, in our belief in how we can change, change practice. And you know, being able to treat patients before they relapse to drive up that cure rate, is really something that cema-cel, we believe, is very uniquely, set up to do. And so we're, we're terribly excited about this upcoming futility analysis to see whether we're on the right track here and hopefully, you know, one step closer to making a big difference for patients, across the treatment spectrum, not just in academic centers or ATCs, but right where they're diagnosed with their local oncologists. This really will be a revolution for patients. Got it. Absolutely, and I share your excitement. Looking forward to the data. Well, thank you so much, Zach. This has been wonderful, incredibly informative, and I really thank you for your time here today. Operator, with that, we can go ahead and close the call.