Allogene Therapeutics at Jefferies Conference: Delays and Optimism

On Wednesday, 04 June 2025, Allogene Therapeutics (NASDAQ:ALLO) took the stage at the Jefferies Global Healthcare Conference 2025. The company discussed strategic advancements and challenges in its Alpha-3 study of Semacel for DLBCL patients. While a delay in the study’s timeline was announced, confidence in achieving enrollment targets was reiterated.

Key Takeaways

• The Alpha-3 study’s first milestone is delayed to early 2026 due to site resource issues.
• Over 250 patients have consented to MRD testing, showcasing strong demand.
• The interim analysis will focus on safety and MRD negativity conversion.
• The study’s primary endpoint is event-free survival, a key measure in similar CAR T studies.
• Allogene remains optimistic about transforming the standard of care for MRD-positive DLBCL patients.

Operational Updates

• The Alpha-3 study is ongoing, with its first milestone postponed to the first half of 2026.
• Enrollment targets around 240 patients, with some already receiving Semacel treatment.
• The study involves a unique approach with three arms: lymphodepletion, without lymphodepletion, and an observation arm.
• Education is required for investigators and patients due to the study’s complexity.

Future Outlook

• Allogene aims to achieve its first important milestone, lymphodepletion selection, by early 2026.
• The interim analysis will assess safety and MRD negativity conversion.
• If successful, the study could redefine treatment standards for MRD-positive DLBCL patients.
• Allogene anticipates MRD becoming a standard endpoint in future clinical trials.

Q&A Highlights

• The delay in the study’s milestone is due to site resource issues and complex patient flow.
• Strong demand is evident with over 250 patients consenting to MRD testing.
• The study compares two lymphodepletion regimens: FLU-PSY and FLU-PSY with ALLO-647.
• The primary endpoint is event-free survival, a clinically validated measure.

Readers are encouraged to refer to the full transcript for a detailed account of the conference discussion.

Full transcript - Jefferies Global Healthcare Conference 2025:

Mike, Panel Host: We are very pleased to have the CEO of Allogene here with us, Doctor. David Chang. Allogene, despite the volatility of the markets, is obviously continuing to execute on the, I call it phase three, but pivotal phase two randomized study in a consolidation approach to first line DLBCL. And they have been working on that study, but also had some recent announcements on the last earnings. And so maybe it would be a good place to start if you could tell us about the study and particularly the developments on the quarter and how we should interpret that because, you know, the market was a little bit concerned about the delay.

But you you say that no, we got plenty of people enrolling and coming on to the study. So tell us about the execution of the study and the recent developments.

David Chang, CEO, Allogene: Yes. So first of all, Mike, thanks for having me on your panel. And the study that you are referring to is our alpha three study of Semacell in the frontline consolidation setting. One thing, just as a reminder, the approach that we are making in that study is applying the right product, Semacel, where we have shown very compelling efficacy data as well as safety data coming from our Phase one study into the right patient population. So these are patients who have completed frontline RTRA treatment but still remain MRD positive.

And there is the selection of the patient based on MRD testing and then also at the right time, which is treating them before their disease manifests in a way that jeopardizes the safety of the patients or patients’ well-being. So in terms of the strategy of the Alpha-three program, this is very well established and recognized by not only the hematologists and investigators involved in our study, but also by the investor community and also is very well liked by the FDA in terms of design. One thing about that study as we, you know, rolled out in The United States is that study design in itself is somewhat unique. There has been no such design as a frontline consolidation. It’s usually adding onto the frontline on top of the R CHOP.

So investigators have been telling us this may require a little bit of education, patients, and other sub investigators alike. And, you know, we sort of heard that numerous times, but as we were operationalizing the study, we definitely come to appreciate that it does take a little bit of time. So, part of the communication that we announced at our last earnings call is pushing out our first milestone by about two quarters to the first half of twenty twenty six. And main reason for us to do that is that initial ramp up that took more time than that was needed. That was mainly coming from clinical sites even after they complete all the regulatory paperwork to be qualified as activated in terms of actual contribution of the patient screening took a little bit of time.

This all had to do with the site resource issue more than anything else. And then the second part is the design in itself. There is a flow of the patients. The patient gets identified for the MRD testing first and they have to wait until they complete the R CHOP regimen. It can be up to about eighteen weeks.

And then they undergo MRD testing before they can be randomized. So the patient flow has been likewise, it takes a little bit of time. Specifically

Mike, Panel Host: you gave us some numbers, right? So you gave some numbers on the call as to how many people you have visibility on or had signed consent to get tested.

David Chang, CEO, Allogene: Yes.

Mike, Panel Host: Right? So what what were those numbers and how does that play into how many could get enrolled?

David Chang, CEO, Allogene: So we have said that right now, this was at the time of earnings call, which was a couple of weeks ago, about more than two fifty patients have consented to undergo MRD testing. And that number is growing pretty rapidly. And I think that is a really good indication for the demand of the study, which investigator has been telling. And it’s actually materializing and we are seeing it from the patient consenting. So now how does that eventually translate into patient being randomized to the alpha-three study?

They have to wait a little bit, they have to undergo MRD testing, and then after that they get randomized to the alpha-three study. So it does take a little time and we expect in terms of getting to enough patients to make the lymphodepletion selection, which is our first important milestone, first half of twenty twenty six, we feel very confident that we can get there.

Mike, Panel Host: So let’s walk through some of that math. So you said two hundred and something, how many?

David Chang, CEO, Allogene: More than two fifty.

Mike, Panel Host: More than two fifty people have consented to get MRD testing. That is obviously a funnel because those people would then what percent would then be MRD positive after R CHOP? And I think the number could be what? So the R CHOP and then they have to actually not have gotten a CR. And then of those people, walk me through some of that math.

David Chang, CEO, Allogene: Yeah, so of the people who have consented for the MRD testing, some of them would not be eligible to undergo MRD testing. Those are patients who did not get a good enough response from the R CHOP regimen. These are so called primary refractory large B cell lymphoma And they should really go to the next line of therapy.

Mike, Panel Host: What percent of people would be eligible to get MRD testing?

David Chang, CEO, Allogene: We currently estimate the majority. We haven’t given the exact number till we figure out more actual numbers from our clinical study, but we expect to be a large majority of patients will undergo MRD testing. And based on all the data that’s available, from the retrospective sample analysis, we expect one out of five patients who undergo MRD testing to be MRD positive. Now those are the patients who will be eligible to go on to the Alpha-three study.

Mike, Panel Host: Now are the people that consented, are these people that have not yet begun the R CHOP? Are these people who are in the middle of the R CHOP? Where are they in the stage of that where they consented on this form?

David Chang, CEO, Allogene: So most patients would have already started R CHOP treatment.

Mike, Panel Host: And

David Chang, CEO, Allogene: in terms of consenting can happen while they are, you know, undergoing frontline, you know, first cycle of R CHOP to when they complete the R CHOP.

Mike, Panel Host: Okay.

David Chang, CEO, Allogene: So it’s essentially about the eighteen week period, which is the the length of the six cycles of R CHOP.

Mike, Panel Host: And, I think we have gone through this before, but most people do get a durable CR so that most people would be eligible to at least be considered for the MRV. Is that fair?

David Chang, CEO, Allogene: That will be a fair statement.

Mike, Panel Host: Yes. I’m going throw out a number like I think eighty percent do get a durable CR so that we could do some testing. Is that fair? It’s interesting.

David Chang, CEO, Allogene: I think you are in the right ballpark So

Mike, Panel Host: then of the eighty percent, if they all do get the testing, then one out of five could be a MRD negative, excuse me, MRD Yes. And therefore they would choose to now move into the study. Is that a fair assessment?

David Chang, CEO, Allogene: You know, one thing I’ve learned from you is I’m not gonna argue the math with you.

Mike, Panel Host: I’m okay in math. I’m decent in math. But to be fair too, because we wanna make another adjustment which

David Chang, CEO, Allogene: is,

Mike, Panel Host: you know, once they get there, they do still have to then agree to now go under the protocol to actually get the CAR T.

David Chang, CEO, Allogene: Yes.

Mike, Panel Host: So it’s just not like, okay, we got a test, you did the test. We’re not consented to the test, then you got to consent to the drug. Is that a fair statement?

David Chang, CEO, Allogene: Yeah. The way that you have described funnel is exactly how we think about it. We start with as many patients as possible. The funnel, the angle of the funnel, we will determine as we do the study. But, in terms of, you know, the actual number that could end up in the study, we still believe that majority of patients who consent to the MRD testing can potentially end up in our study.

Mike, Panel Host: Right. I’ll put it this way. If they do become MRD positive, not negative, Stuff, minimalization. That many, most is your number, will end up choosing to say, yeah, I would wanna get this drug.

David Chang, CEO, Allogene: Correct. Okay. Especially that’s the part that we had to do a lot of educational part because that concept, you know, just imagine from the patient perspective, when they start R CHOP, most of the conversation is, you know, you have a pretty aggressive lymphoma, but the good story is R CHOP is a very effective After six cycles, your chance of getting a cure is very good. Now from there, just coming in at the end of the R CHOP regimen, by the way, I’d like to you to undergo MRD testing.

Mike, Panel Host: Okay.

David Chang, CEO, Allogene: And if you are MRD positive, you may have to prolong your treatment. Okay, that’s not the most easiest conversation for physicians to have with a patient. So that’s why part of the exercise and implementation that we have done is try to have that conversation early on during the treatment to prepare the mindset of the patient.

Mike, Panel Host: And that mindset is part of where they were educated about this as to why they were consenting for this test. Is that fair? Is to see if they would be eligible for a treatment?

David Chang, CEO, Allogene: Correct.

Mike, Panel Host: Right. It’s not like, oh we’re taking this test and we’re just collecting some data. It was you’re taking this test because you would be considered for this therapy?

David Chang, CEO, Allogene: Because if you are MRD positive Yes. You have an option.

Mike, Panel Host: Okay.

David Chang, CEO, Allogene: Mhmm.

Mike, Panel Host: Alright. And then again, so we can do the math and therefore they would choose to get this off the shelf therapy.

David Chang, CEO, Allogene: Correct.

Mike, Panel Host: Have have have this was a earnings call a few weeks ago. And at the earnings call, it was just an announcement that we’re pushing out the timing of the interim, which we’ll get to in a second. Mhmm. And that interim would be pushed into first half twenty six Correct. From sort of mid.

Now have you actually tested people that are MRD positive? Have they actually gotten the drug and been randomized?

David Chang, CEO, Allogene: We haven’t provided that level of detail but there are definitely a number number of patients have been randomized to the study already and received stem cell treatment. Okay.

Mike, Panel Host: Alright. Good to know. Alright. And so therefore that should be actually picking up now because you, obviously said there was just an initial delay and now those sites have been ramping up. So based on what you’re seeing, can you say here and sitting here in June that things are picking up and you definitely feel very good and on track and feel a lot better than you did the prior earnings call where you guys said this was gonna be on track.

Actually, you guys said it was gonna be a mid readout. That’s supposed to be a catalyst. And then I kind of got slipped up there on the next one.

David Chang, CEO, Allogene: Yeah. I mean, any slippage in timeline is something that, you know, we did not wanna do. And we were watching the study, you know, with Hawkeyes to see when the hockey, you know, hockey puck effect of the enrollment would occur. But at the, you know, by the time we got to the earnings call, we felt that it would be better just to push out the timeline k. To be very transparent with investors about what the study, you know, how the study is performed.

Mike, Panel Host: Sounds like you could be conservative on it. We’ll see.

David Chang, CEO, Allogene: Well, let’s, you know, we already pushed out the timeline. Well, don’t want to do that again. So let’s just keep it as a first half.

Mike, Panel Host: Well, put it this way. It is public disclosure in the k that the interim is based on around 36 patients. Is that fair?

David Chang, CEO, Allogene: As I said, I’m not gonna argue about the numbers or math with Mike.

Mike, Panel Host: It’s in the 10 k. Now, what is the interim? What is it looking at? What is it what is what is the end? Actually, is it a futility?

Is it what what are we testing in this?

David Chang, CEO, Allogene: Yeah. So in term, you know, there is a futility component. But as you know, most futility boundaries are set, you know, pretty low, you know, unless something is fundamentally wrong, you know, with what you’re doing.

Mike, Panel Host: Usually causing harm is one thing.

David Chang, CEO, Allogene: Yeah. So, so, yes, we are looking at, you know, safety. You know, we are looking at, I mean especially keep in mind that the comparison in this study is observation. And we know that CAR T has some safety issues, although that wasn’t so prominent in our Phase I study. But that’s one thing, just for full transparency that we’ll be looking for, any imbalance in safety.

And the second thing that we’ll be looking for is we are enrolling patients who are MRD positive. And how many of those patients convert into MRD negativity? Because the data that’s out there is pretty good that if you are MRD negative, your chance of having a recurrence is very low. So we believe that surrogate biomarker MRD conversion is a pretty good indicator about how the study is going. And so that is how we’re gonna look at the initial instrument analysis.

Mike, Panel Host: Well, if you got thirty six patients, sorry I gotta do a little math, it’s three arms. One is with the lymphodepletion, one is without, and then one’s observation.

David Chang, CEO, Allogene: Correct.

Mike, Panel Host: So observation, I don’t think people are gonna go to MRD negativity by magic luck. Correct. With lymphodepletion, there could be a very good chance that they’re gonna go to MRD negativity based on your hypothesis of how the drug is working, which is getting rid of that last residual disease. And that the arm, I couldn’t say with or without the residual, but the other arm that’s also getting the drug, they should also get it to convert. But you think that with lymphodepletion it could be even better.

You have not said whether or not getting lymphodepletion is a good thing or a bad thing.

David Chang, CEO, Allogene: So here the lymphodepleting And

Mike, Panel Host: honestly I think Wall Street is a little bit confused too. Is it good or bad?

David Chang, CEO, Allogene: Don’t know. Okay, you know, first of all there’s no confusion here. CAR T therapy is always done together with a lymphodepleting chemotherapy.

Mike, Panel Host: Yes.

David Chang, CEO, Allogene: What we are doing in the study is testing two different regimens of lymphodepletion. Fair. Mainly because we are treating patients with a low volume. Minimum residual disease is essentially the patient So if you look at our Phase I data, in the patients with relapsed recurrent, so these are patients with evidence of disease, what we have shown in the Phase I data is complete response rate of about sixty percent.

And if you look at within those patients according to whether they had low volume versus high volume disease, low volume disease patients, the response rate goes up to one hundred percent. It’s a small data CR rate. Yes.

Mike, Panel Host: The CR rate was one hundred percent. I can’t remember how many numbers. There’s a handful. Yeah. Correct.

Yeah. Not only did they all have CR, but it was durable.

David Chang, CEO, Allogene: Correct.

Mike, Panel Host: And therefore based on basic science principle, the lower the bulkiness of the disease, the greater the TSLs are going be able to clear that. And when you got MRD, we’re talking about very small levels of disease.

David Chang, CEO, Allogene: Correct. So, you know, back to, you know, doing the math since this becoming a little bit of math discussion. You know, the first interim analysis when we do it, on each arm, we would like to have about 12 patients per

Mike, Panel Host: arm. Yep.

David Chang, CEO, Allogene: In the control arm, exactly as you said, there should be almost no one converting into MRT negative negativity spontaneously. And in the treatment arm, the range of MRD conversion can be either around 50% to 100%. So that’s the sort of unknown that we like to see as the data matures.

Mike, Panel Host: Based on the fact that you’re adding, I can’t remember the name of the number of the drug, but you’re adding the anti CD52.

David Chang, CEO, Allogene: So that’s ALLO-six forty And

Mike, Panel Host: that’s with the PSY, right? Correct me

David Chang, CEO, Allogene: if get that Yeah, the lymphodepletion regimen that we are comparing is FLU PSY, which is a standard lymphodepletion that’s used in autologous setting. And the second lymphodepletion is full side with allo six forty seven which is anti CD52 antibody.

Mike, Panel Host: Like, and why would that? That’s just to help again further reduce the rejection of the cells and that should may or may not be necessary. That’s your point.

David Chang, CEO, Allogene: Exactly. Especially when the disease volume is so low. Right. That’s something that we have not tested before.

Mike, Panel Host: So here’s what would happen when we get to this. And I gotta be honest because we’re trying to figure out for investors who are looking at this. Okay. Should we buy this and get excited about this event? Because on one hand, obviously, it’s reasonable that the drug study continues.

They’re gonna either pick with or without 547, and we’re gonna continue. We’ve got to get there. We’ve got to make sure Allogene executes and gets there on time. You know, we’ve got to do that first. And then second of all, it seems reasonably obvious that they’re just going to pick one of those arms and keep the observation arm going.

Good news. Thumbs up. You know, you didn’t fail the futility. On the other hand, there’s safety things that could come up. That would only be the only other reason why things are a problem.

I mean, I got this is not your case, but there’s another CAR T company named Cargo, which you ran into a big surprise because the advocacy was no good, but there were safety problems. And that was a big disappointment there. And so given the fact that we’re dealing with fairly healthy patients is other than CRS or other things, right, what are the types of safety things that would pop up that should not be an issue here, but theoretically this is the stuff that you have to check and that’s why we’re doing the interim.

David Chang, CEO, Allogene: Yeah. Exactly.

Mike, Panel Host: What type of safety stuff?

David Chang, CEO, Allogene: You know, these are patients

Mike, Panel Host: who should be reduced because it’s low volume. Precisely. You’re not going to get the type of inflammatory reaction CRS because you would see in third line DLBCL.

David Chang, CEO, Allogene: So if you look at our relapsed refractory, dataset, when you look at the cytokine release syndrome or the neurotoxicity, we had no grade three events.

Mike, Panel Host: No grade three events.

David Chang, CEO, Allogene: Yeah. There were some grade one or two which are milder ones. And then there was also a grade three infection rate that was much favorable than what autologous CAR T has shown. The exact number is in the patient cohort that’s relevant to the study. We had about eighteen percent in those autologous CAR T programs.

You know, the rate was somewhere in the twenty percent range. The infection most likely is coming from the lymphodepletion more than anything else. So those are the kind of safety issues that we are dealing with.

Mike, Panel Host: Now that’s still although these patients are definitely healthier than third line DLBCL, how do you think about infection risk because technically you’re putting people at risk of infection? Although yes, obviously we’re supposed to get a therapeutic benefit too. But the FDA wouldn’t want to, people don’t want to see things like that without evidence of efficacy.

David Chang, CEO, Allogene: I mean, first of all, you’re giving flu sigh. So there is always infection risk. But infection, as long as that’s within the range that we have seen in the relapsed refractory setting, I don’t think that is an issue. Yeah, I would agree that if there’s no efficacy associated with the infection risk, that’s a different story. But all the data would indicate we should have a very good conversion Yes.

So I mean frankly this is one of the reasons that a lot of investigators involved in the study who know the phase one data so well said, you guys, this study is so de risked. I mean, you know, you have to do something wrong to fail

Mike, Panel Host: That’s what I’m saying. Like, what would go wrong? Well, it’s a safety problem. Something would happen. That would that would derail a situation.

But, again, this feels fairly just. Now, if we march forward then, what is because I think I can predict that one of those arms is gonna go forward versus observation. How many, how much more time after that, those 36 do we need to continue to enroll to get to the efficacy endpoint?

David Chang, CEO, Allogene: So the efficacy endpoint you’re talking about is the next interim analysis, which is looking at the clinical endpoints. So we will be doing another interim analysis. So this is statistically powered interim analysis that will look in the event free survival, which is the primary endpoint. We will provide at the time of the first interim analysis based on all the projections that we can gather from the enrollment about when they will occur rather than giving you, numbers that is there are so many sort of

Mike, Panel Host: unvalidated What’s the target? The target is that the enrollment for the interim is 36. What is the number of patients needed for the actual primary?

David Chang, CEO, Allogene: So we haven’t discussed about, disclosed about what those numbers are. We are intending to enroll about two forty patients to the study. And event free survival, if you look at it, usually you’ll be looking at forty to fifty percent having the event before doing the, you know, the primary analysis. So that is the norm at which most statisticians will think about when to do the primary analysis. Sure.

And then interim analysis will happen when those events are either about forty to fifty percent.

Mike, Panel Host: Sure. You plan to enroll two forty, Certainly, an interim could happen on fifty percent of the patients. And there is an interim. And are you you are you would plan to spend alpha on that because you believe that it should hit on that. Right?

That’s that’s the thing.

David Chang, CEO, Allogene: We are spending some alpha

Mike, Panel Host: on that. Mhmm. Yeah. Okay. Alright.

So then another question that would come up too, and this is important in the last five minutes or so, is if this takes place and if it’s positive and we get to all that, that CBER, Bene Persaud, and obviously, just CAR T in general, there have been provocative comments by CBER, although that his account has been deactivated and said that’s in the past, you know, about MRD and about CAR T. Now that was in myeloma, but these are comments that worry investors because they believe that certainly in a healthier population here too, because that was also the concern was that cartitude forwards in healthy. So in a healthier population, how should we think about MRD? This is actually We’re trying to get people to go to MRD activity, but, this is, the idea of MRD.

And in the absence of significant safety database, how we should be how should we think about that with this type of FDA?

David Chang, CEO, Allogene: Yeah. I mean, you know, from that regard, we feel very comfortable about the study design and endpoint that we are using. So just to make it clear, alpha three study is a randomized control study and that’s a gold standard at which you do any kind of study. And, you know, for CAR T studies, that’s pretty unusual. Number two, we are using very well defined patient population who are at high risk and we use MRD assay to risk stratify and select the patients.

MRD is not a clinical endpoint that we are using. The clinical endpoint that we’re using is event free survival, which is the same endpoint that has been used in the second line study of Yescarta and BRIANZI that led to the approval of those, drugs. So there is a regulatory precedent of using event free survival for drug approval.

Mike, Panel Host: What is the

David Chang, CEO, Allogene: And and also, you know, in in our study, the MRD conversion Yes. Is, that’s not the primary endpoint. We use that to inform internal decision making

Mike, Panel Host: Right.

David Chang, CEO, Allogene: But it’s not how we’re gonna make an argument with the agency about the benefit of semi cell

Mike, Panel Host: and this Right. The the primary endpoint is not conversion of MRD, positivity and negativity. The primary endpoint is event free survival.

David Chang, CEO, Allogene: Correct.

Mike, Panel Host: You’ve obviously believed that when you convert someone to MRD negativity that that person obviously will have a longer event free survival.

David Chang, CEO, Allogene: Exactly.

Mike, Panel Host: Okay. So that is the primary endpoint. And by the way, you believe that if you don’t convert to MRD negativity, which the observation arm definitely is not going to have a lot of those, that they’re going to fall off based on the Kaplan Meier curve of some literature that they should fall off within six to twelve months. Because if they go from, if they are MRD positive, the data suggests that those people do convert pretty quickly. It’s just that nobody tests them.

David Chang, CEO, Allogene: Yeah. That’s a growing data. I mean, that’s the initial, you know, data set that our diagnostic partner Foresight has published. And they also recently updated using different samples, you know, basically verifying what they have said before. So MRD positivity at the end of R CHOP treatment indicates that your chance of having a disease recurrence is very, very high.

Mike, Panel Host: Okay, So then this is let me ask the next question then. The next question is, what is the clinical, I haven’t memorized it. What is the clinical benefit of someone who is, MRD negative? So if we can get them MRD negative, What do you think their event free survival should be versus the person? I think you just said, if you do not, then you’re going to progress pretty quickly, like within six months.

So what do you think the EFS curve would be for the drug arm? Pretty much flat or what? That you you

David Chang, CEO, Allogene: So the modeling that we are doing is that once they are converted into MRD negativity Yep. They’re they will remain recurrence free.

Mike, Panel Host: For how long?

David Chang, CEO, Allogene: That we will have to see. I mean, you know, ultimately, if you look at the existing data, they will say for the next two to three years your chance of disease recurrence

Mike, Panel Host: is How do know that just by looking at people who were on R CHOP and who are MRD negative? What is that?

David Chang, CEO, Allogene: That’s a one line of evidence. I mean, that’s a that’s a published data. Another line of

Mike, Panel Host: If you get our CHOP and your MERD negative, your EFS is like a few years.

David Chang, CEO, Allogene: It’s like flat. I you don’t you don’t have a recurrence.

Mike, Panel Host: Right. Okay. So that’s one line of evidence.

David Chang, CEO, Allogene: So the second line of evidence is coming from retrospective analysis of people who are treated with CAR T therapy in relapse recurrent setting.

Mike, Panel Host: Okay.

David Chang, CEO, Allogene: The ones who achieve MRD negativity, they are the ones who have a prolonged durability of the response that goes beyond.

Mike, Panel Host: Right. So if you look at Yescarta or others, right, is what we’re talking about.

David Chang, CEO, Allogene: And these are published Okay.

Mike, Panel Host: The people who get a CR with MRD negativity, they have significantly better EFS than people who are CR without MRD negativity? Let’s just start with that.

David Chang, CEO, Allogene: I mean, I can tell you the available data would indicate patients with CR but MRD positive Yep. They will relapse quickly.

Mike, Panel Host: Interesting.

David Chang, CEO, Allogene: The reverse is also true if you have MRD negative.

Mike, Panel Host: I think that’s because most people on Yescarta, if they do get the CR, isn’t most of them MRD negative? What percent is that? You wouldn’t know. Seventy percent, sixty percent? It’s gotta be most because people get a CR DSCAR net.

They get past the first three months. We know that they can have a long duration.

David Chang, CEO, Allogene: Yeah. So, you know, if you look at most. Not the ESCO. Oh, you know, if you look at across all the approved, autologous CD19 CAR T, the initial CR rate is between fifty percent to sixty percent. Right.

However, over a period of next six months, some of them do progress it

Mike, Panel Host: comes down to like thirty five percent. So fifty five coming out of should I say most, I’d say half. And that’s your delineation between being MRD negative and MRD positive.

David Chang, CEO, Allogene: And also the retrospective analysis would, in a way, predict what CRs on insufficient CRs with a CAR T therapy.

Mike, Panel Host: So we just went to ASCO and it’s interesting because one of the, well, it was the oral plenary at ASCO. The oral plenary on Sunday was in breast cancer and they talked about testing for ESR positive molecular breast cancer just by ctDNA. Think about that. That’s kind of interesting. No radiographic tumor, just looking at molecular testing of ctDNA, kind of like MRD positivity.

And then if you do, we switch you to a amazing new SERD which would treat you rather than observation. I’ll check that out. And so that I had a huge seven month PFS, hit the primary endpoint hazard ratio point four four. Isn’t that kind of analogous to it? Their only question in the discussion, realizing that we all agree it was a positive study and they said, you know, we’ll consider how that could be used if approved, that it’s almost like we gotta test for PFS two.

So here, her big question is, all of you waited for the person to progress and there were an observation after six months. What happens if I give them, Allogene after that or Yescarta? How would that PFS look? That’s an interesting one. We gotta spend time thinking about that in another time.

David Chang, CEO, Allogene: Precisely. I think that’s a secondary question after we conduct the alpha three study. If the data is positive, there will be questions that are coming up on how to best utilize the MRD information.

Mike, Panel Host: And that’s if they did progress, isn’t if they did, isn’t the standard of care to then get Yescarta in the quote unquote second line? That is correct. And that’s is that what people are going to ultimately do in your study? Because if they do progress in their observation, they don’t cross over to Allogene. They would go and get probably Lysarta.

Yes.

David Chang, CEO, Allogene: So if you are in the observation arm and also, you know, it also applies to people who are in the treatment arm. If they have a progression event, they can go into any of the, you know, available treatment. Obviously if you are transplant eligible and if you can get access to CAR T, there will be an option. If not, there’s a second line chemotherapy regimens that are used including, so called, you know, bone marrow transplantation. So

Mike, Panel Host: that would be the way to sort of look at PFS two if that was the case, but that would be getting, another another cartoon.

David Chang, CEO, Allogene: Yeah. And and frankly, in the breast cancer, you know, where the follow-up is much longer, you know, you can talk about PFS two, but in the, you know, lymphoma setting, it will be more like overall survival.

Mike, Panel Host: Overall survival. Okay. Well, first of all, thank you very much again, David, for spending time. I thought we did a great job walking through the dynamics of that and why your results should be positive both at the interim, well futility and then the interim and why, it would be transformative if we can get people to MRD negative. So I

David Chang, CEO, Allogene: I mean, I would just say, you know, Alpha three is really innovative design and the field is moving to MRD based stratification. And I do believe ultimately MRD will be used as an endpoint. Yep. But how long it will take? And it will take some time.

Mike, Panel Host: Well, usually it starts with a trial that ran the results and showed you that it happened. That’s how you change the standard

David Chang, CEO, Allogene: of Yeah. It’s it’s at the very beginning and we are at the forefront of the beginning.

Mike, Panel Host: Thank you very much, Dave.

David Chang, CEO, Allogene: Appreciate it. Alright. Thank you. Thanks for the insightful questions.

Mike, Panel Host: Thank you.

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