Allogene Therapeutics at Citi’s SMID Call Series: Strategic Insights

On Thursday, 02 October 2025, Allogene Therapeutics (NASDAQ:ALLO) participated in Citi’s SMID Call Series 2025, presenting a robust strategic overview. The company highlighted promising developments in its pipeline, particularly the ALPHA-3 trial for diffuse large B cell lymphoma (DLBCL) and the ALLO-329 autoimmune program, while also addressing enrollment challenges and financial sustainability.

Key Takeaways

• Allogene’s ALPHA-3 trial targets a $5 billion global market for DLBCL.
• The ALLO-329 program features innovative "Dagger" technology, aiming to treat autoimmune diseases without lymphodepletion.
• The company anticipates critical data readouts in the first half of next year.
• Allogene has secured a cash runway extending into 2027.
• Enrollment strategies have improved, boosting confidence in meeting trial goals.

Financial Results

• Allogene’s financial position is strong, with a cash runway extending into 2027.
• The ALPHA-3 trial represents a significant market opportunity, estimated at $5 billion globally.

Operational Updates

ALPHA-3 Trial:

• Design: Patients are randomized to observation or SEMA cell treatment post-MRD positivity after R-CHOP therapy.
• Challenges: Initial difficulties in integrating MRD testing and coordinating care between specialists.
• Mitigation: Improved patient identification and enrollment rates through best practices and site performance enhancements.
• Futility Analysis: Expected in the first half of next year, targeting a 30% or greater MRD conversion difference.
• Enrollment: Improved rates and confidence in meeting goals, with 220 patients to be randomized.

ALLO-329 Program:

• Design: Dual CD19/CD70 targeting CAR T for autoimmune diseases.
• Technology: "Dagger" aims to eliminate the need for lymphodepletion.
• Phase 1 Study: Includes dose escalation in parallel arms, with and without low-dose cytotoxin lymphodepletion.
• Flexibility: Basket design allows for enrollment across various autoimmune conditions.
• Initial Readout: Anticipated in the first half of next year.

Future Outlook

ALPHA-3 Trial:

• Futility Analysis: Results expected in the first half of next year.
• Potential Impact: Aims to transform DLBCL management with MRD-driven treatment strategies.

ALLO-329 Program:

• Expansion: Aggressive growth planned upon proof of concept, with potential beyond rheumatology.

ALLO-316 Program:

• Partnerships: Actively seeking partnerships to advance treatment for solid tumors, particularly in kidney cancer.

Q&A Highlights

• MRD Testing: Around 20-25% of patients remain MRD positive after R-CHOP, with MRD positivity predicting relapse.
• SEMA Cell Efficacy: Phase one study showed a 100% complete remission rate in patients with lower tumor burden.
• Commercialization: SEMA cell is designed for community oncology practices, with about 50% of sites being community-based.

Readers are encouraged to refer to the full transcript for a detailed understanding of Allogene’s strategic initiatives and future plans.

Full transcript - Citi’s SMID Call Series 2025:

Sam Semenko, Senior Biotech Analyst, Citi: Good afternoon, and thank you for joining. I’m Sam Semenko, one of the senior biotech analysts here at Citi, and it’s my pleasure to be hosting Allogene’s executive vice president and CMO, Zach Roberts, as a part of Citi’s SMID Biotech c suite virtual fireside chat series. Zach, welcome, and thank you so much for joining us today.

Zach Roberts, Executive Vice President and CMO, Allogene: Thanks so much for having me, Sam.

Sam Semenko, Senior Biotech Analyst, Citi: If you if, anyone on live on the call has any questions during the session, please go ahead and email them to me directly at samantha.semenko@Citi.com, and I’d be happy to ask them on your behalf. So, Zach, why don’t we, sort of jump right in? Maybe at a high level, let’s just talk about Allogene’s pipeline and where you are today as a company.

Zach Roberts, Executive Vice President and CMO, Allogene: Sure. So Allogene, was founded in 02/2018. We have been, since the beginning, a, a company focused on allogeneic cell therapies initially for oncology indications, and now we’ve recently expanded into autoimmune indications as well. We currently have three clinical programs that are ongoing. We’ve got our lead pivotal program with its CD19 off the shelf allogeneic CAR T product called SemiCell.

And this is being developed in a very unique indication in what we call frontline consolidation for large B cell lymphoma. And we’ll have plenty of time, I think, during the call to talk more about this ALPHA-three trial. So I’ll save that for later. The second program, another oncology program, is a solid tumor program in advanced and metastatic renal cell carcinoma. This product is called ALLO-three 16, and it’s targeted CD70.

And we recently showed the culmination of a Phase I program at ASCO just earlier this summer. And very exciting data in that program. We saw thirty one percent overall response rate in patients with multiply relapsed refractory metastatic RCC. And these responses were quite durable, really a first for the field, especially as it pertains to allogeneic cell therapies, again, another off the shelf product. And then the third and final clinical program is our autoimmune program, as I alluded to previously.

This product is new and novel in a few ways, also healthy donor derived off the shelf, but it’s the first dual targeting CAR that that targets both c d 19 and c d 70. And this was really designed, to enable targeting both pathogenic b cells, but also pathogenic t cells. And these are T cells that specifically upregulate CD 70 on their surface. CD 70 is a marker of T cell activation. And there’s another unique feature of the CD 70, molecule, CAR molecule, And then it incorporates what we call the Dagger technology.

And a way of shorthand in thinking about what Dagger is, is it’s essentially built in lymphodepletion. And so these cells, once we infuse these allogeneic CAR T cells, resist the patient’s immune system from rejecting them. And by doing that, they actually garner a proliferative burst. So they begin to expand on their own, and we were actually able to show in that kidney cancer program that we can do this with markedly less lymphodepletion that is generally required for allogeneic cell therapies. So I share this to illustrate one of the defining features of this three two nine program is that we are bringing this to autoimmune patients with less or even no lymphodepletion at all and relying entirely on this built in lymphodepletion that we call the dagger effect.

So that’s a a very high level summary, Sam, of Allogene’s history as well as our current pipeline.

Sam Semenko, Senior Biotech Analyst, Citi: Yes. Thank you for that. You gave us a lot to work with there, and I you’re correct. So let’s let’s start with the stem cell alpha three trial. You know, you you mentioned this is a unique indication.

It absolutely is. But let let’s talk a little bit about that opportunity of that unique, indication. What’s the size of the market, and and where do you think that, SEMACELL could really deliver in that space?

Zach Roberts, Executive Vice President and CMO, Allogene: Yeah. So one of the exciting things about this trial is that it incorporates a new disease assessment tool, that is rapidly becoming standard in diffuse large B cell lymphoma, which is called a minimal residual disease, or MRD. And what MRD is enables a clinician and a patient to do is even in patients who appear to be in remission, they can get this additional very sensitive, very specific blood test. So it’s not a scan, it’s a blood test that measures circulating tumor DNA. And if circulating tumor DNA is found in the blood, that is a very strong indicator that these patients will have their cancer come back.

And so and sometimes it’s, you know, very quickly and sometimes it actually can be many months. But it gives both doctor and patient a better understanding of what to expect from their cancer. So with that kind of foundation, we looked at the market opportunity here. And even incorporating what we believe will be the uptake of MRD in the coming years, we assess this to be approximately a $5,000,000,000 global opportunity because it essentially will capture most of the patients, if not all of the patients, who eventually go on to relapse with their DLBCL and are currently being treated with salvage regimens like autologous CAR T. So we really have kind of, in a manner of speaking, sort of leapfrogged the second and third lines and found ourselves right between frontline and second line.

So it’s a fairly large market opportunity globally.

Sam Semenko, Senior Biotech Analyst, Citi: Okay. And there are no other cell therapies or any other drugs targeting this population currently, correct?

Zach Roberts, Executive Vice President and CMO, Allogene: Currently, no.

Sam Semenko, Senior Biotech Analyst, Citi: Okay. Do we have any indication that there may be others entering the space or that just hasn’t happened yet?

Zach Roberts, Executive Vice President and CMO, Allogene: So, you know, we spend an awful lot of time talking to, lymphoma physicians, both global KOLs, but also, community doctors. And what we we find is nearly universally, people think that this is a very forward looking study design and one that stands probably the best chance at improving frontline outcomes in large b cell lymphoma for the last twenty five years. So we we believe this is a good idea. We think it’s a solid, study design, and we expect there will be competition. We hear rumors from time to time that there may be something in the works, but so far, we haven’t had anything concrete come to our our awareness.

Sam Semenko, Senior Biotech Analyst, Citi: Got it. Okay. So then maybe let’s talk a little bit about the study design, and maybe you could be helpful to walk through the patient flow and of the study design and how they get from, you know, screening to enrollment and into the study.

Zach Roberts, Executive Vice President and CMO, Allogene: Sure. So before I get there, it probably makes sense to just level set on on what a typical patient journey is today in the current standard of care with a new diagnosis of large B cell lymphoma. So patients, you know, notice symptoms, a lump, night sweats, what have you. They come to their doctor, they get a biopsy, they’re found to have diffuse large B cell lymphoma. And then almost everybody, certainly in The United States, at least two thirds of patients, maybe a little bit more, will get started on a very standard, very old regimen called R CHOP.

And that’s actually five different drugs. Each drug, know, has a letter in R CHOP that stands for the drug. And that’s given for six cycles every three weeks, one cycle every three weeks. And most patients, about ninety percent of patients who are treated with this or similar regimens, will achieve a remission, meaning that their cancer is in better shape at the end of this than it was when they started. And most of those patients will be in what we call a complete remission, meaning that their their their scans are completely clear.

There’s no evidence of residual tumor. About so the remaining ten percent will have what’s called primary refractory disease. Those patients are, frankly, in in rough. In a if they’ve got a sort of a tough road ahead, they will go directly to a second line salvage regimen like autologous CAR T or bone marrow transplant or increasingly a bispecific based regimen. But for the the patients who are in remission, about two thirds of those patients will actually be cured.

They will they will never hear from their their cancer again, and one third will actually have their cancer come back. So, it’s really at that end of therapy, at the end of the six months, that when you have a clean PET scan or a scan that suggests that you’re in remission, that, you know, that PET scan actually is not a very good disease assessment tool. There’s false positives. There’s false negatives. We’ve known about these for decades, but it’s the best tool that we currently have that is widely used.

Where the MRD tests are beginning to make major changes is if you layer on top that PET scan an MRD test of these very specific performance characteristics, it will significantly improve your ability to prognosticate or see the future of what’s going to happen. So let’s say a patient has a complete remission by PET scan. If they get an MRD test and it’s positive, we are almost, we’re about ninety percent sure that that patient’s tumor is gonna come back. They are going to relapse. So even though a PET CT is showing that these patients are clear to their disease, we know that their trouble is ahead.

And conversely, if you have a PET scan that remains positive on some small amount, but their MRD test is negative, we actually are very confident, again about ninety percent or so, that these patients will actually never relapse. And so those patients are very good to observe. So that’s the frontline care. You know, we won’t talk too much about the second and third line, but just to round out this conversation, patients, even if they achieve a remission who are destined to relapse, will go for some number of months, and then their disease will come back, and that is when they’re eligible for a second line regimen. And when I say come back, I mean they have PET scan and or symptoms that illustrate that their tumor has come roaring back.

And that is actually a clinical emergency and those patients need to be treated right away, which is, you know, one of the challenges that faces the autologous CAR T in that setting, which is currently the best we have to offer. But trying to get all that set up, in the context of a rapidly progressing tumor, can sometimes be a bit of a challenge. So that’s really the focus of alpha three is if we treat those patients at the time of their MRD positivity, we are able to prevent that relapse from ever occurring.

Sam Semenko, Senior Biotech Analyst, Citi: Before I let you go into the design of the study, I do have a client question that came in. They’re asking what percentage of patients will remain MRD positive after R CHOP? A limited number of studies show twenty percent to twenty five percent MRD positive. So they’re looking curious how you’re thinking about that percentage.

Zach Roberts, Executive Vice President and CMO, Allogene: Yeah. So that’s about right. If you take a single MRD draw at the end of frontline treatment, that’s a reasonable number to to guess, that somebody is about twenty percent likely to be MRD positive even though they’re in remission. What we do know is that pretty much everybody of course, nothing is a 100%, but pretty much everybody who eventually relapses will turn MRD positive before that clinical relapse. It’s a question of whether we’re actually measuring that MRD positive that MRD status at that time.

But as these tests begin to gain support and backing and are increasingly being paid for by by insurance, it’s likely that MRD will be become part of the longitudinal assessments that’s performed on these patients, not just PETCT. So these patients will, even if they’re MRD negative at the end of frontline treatment, they will at some point turn MRD positive prior to a relapse. So even though it’s 20, which is not exactly the total number of patients that we do expect to have their tumors come back, it’s quite likely that that remainder will actually turn MRD positive prior to that relapse.

Sam Semenko, Senior Biotech Analyst, Citi: Got it. So it’s a sensitivity of the test or just a just a marker of when you have enough of that tumor that MRD positivity can then be detected. Right now, for alpha three, you’re you’re getting them right after they’re, you know, cleared in in remission of some sort, then they get the MRD test right after that. Is is that correct?

Zach Roberts, Executive Vice President and CMO, Allogene: That’s correct. And I’m just noticing my camera is getting a little blurry, and my apologies for that. Let me just turn it off and turn it right back on. That seems to fix the problem. I don’t know what’s going on with it, on this Thursday morning.

That’s that’s thank absolutely you, Tim. That’s absolutely correct. So we are we are performing the MRD test, just a short number of weeks after the the, final cycle of that R CHOP regimen or a similar, regimen like Pola R CHIP, is completed. So we are Okay. At about the time that that end of therapy PET CT, which is currently standard, that’s when we do this MRD test.

Sam Semenko, Senior Biotech Analyst, Citi: Got it. So so if that twenty to twenty five percent ends up being accurate, that’s about the patient population that you could pull from to potentially enroll into alpha three?

Zach Roberts, Executive Vice President and CMO, Allogene: Correct. But but Okay. We actually we actually believe that the commercial opportunity is more likely gonna be reflected by any MRD positive patient regardless of the timing, of their last line of therapy.

Sam Semenko, Senior Biotech Analyst, Citi: No. That makes sense. Okay. Thank you for that. So so then maybe let’s just talk about the journey into alpha three.

So they have been tested or they finished their R CHOP. They’re in the sites being tested for MRD. They come back MRD positive. You know, how do you get these patients enrolled effectively into the study?

Zach Roberts, Executive Vice President and CMO, Allogene: Yeah. So the once they’re MRD positive, their prognosis is communicated, to them by their physician and say, okay, this is not good news, frankly, means your tumor is very likely to come back. At that point, they will sign informed consent for the trial and will undergo a few disease sort of screening assessments to ensure that they’re appropriate for clinical trial enrollment. And then once those are complete and the patient’s eligible, they are randomized into the study. And then the study design currently is a one to one randomization either into the current standard of care for MRD positive patients who are in remission.

And this will be my opportunity to say that currently MRD is an experimental diagnostic tool. It is not baked into any recommendations for treatment decisions. So the current standard of care in a patient who is in remission is to observe regardless of their MRD status. So that is the the the control arm in alpha three is is watch and wait or very close observation. Or they get randomized into the other arm, which is treatment with fludarabine cytotoxin based lymphodepletion and a single infusion of our off the shelf c d nineteen CAR T cell, SEMA cell.

Sam Semenko, Senior Biotech Analyst, Citi: Got it. Okay. And I think, you know, one of the biggest questions I get from investors is how are they going to enroll this study given it is a very novel indication. You’ve just said that the standard of care is to not treat. I know you have a number of sites, both community and academic.

You know, I’m curious what what are the challenges that you’ve seen in enrollment, and what have you done for mitigating? And I guess if there’s an update you could provide today of how that enrollment is going in at a high level, that that I think would be quite helpful.

Zach Roberts, Executive Vice President and CMO, Allogene: Sure. So I would say that the you know, every study has its challenges. Every single clinical trial, there are growing pains when you first launch, and alpha three is, of course, no different. We are doing a lot with alpha three. We are we are testing a novel modality.

It’s CAR T cells, it’s off the shelf CAR T cells. We are also implementing as part of eligibility determination this MRD test, which is currently not standard. I will say that it is rapidly becoming more widely used. When we first started, excuse me, talking about alpha three maybe two, two and a half years ago with doctors, we found that very few of them were using any MRD assessment as part of their standard patient management. We’re we see that, you know, anecdotally, but also in in sales information from MRD developers that this is becoming more widespread.

But in the early days of alpha three, we had to really educate about the utility of MRD and and why a doctor who has been giving our job in assessing disease with PETCT for decades, why they suddenly would layer on this additional test. So we had to build support around the MRD. Many, many doctors are early adopters and they’re super enthusiastic about MRD, and so they loved alpha three right out of the gate as soon as we started talking about it. But then also educating the patients that it’s not just about your PET scan. There is an additional piece of information that we need to collect.

And changing that mindset with both doctors and and patients that a PET CT is not telling you the whole story. So that was part of the early challenge that we faced and just really implementing this study. There are some other operational issues like in The United States, CAR T cells are generally given by transplant doctors and R CHOP is generally given by lymphoma doctors. And at many academic centers, those two groups are separate. Oftentimes, they don’t even sit in the same team rooms.

So, you know, the the study might sit in CAR T in the transplant group, but we needed to facilitate daily communication between the lymphoma doctors and the CAR and the CAR T group so that we could get the the MRD screening rates up to where we needed them to be. So it took us a few months to figure all that out and then and then deploy sorry about my camera again, Sam. Let me just do this again. And then deploy mitigation strategies. And so that really was sort of 2024, early twenty twenty five.

We since since those mitigation strategies have been implemented, we not only have improved performance of the existing early sites that came online that were so eager, but also as new sites have come online, we have brought to them kind of a best a package of best practices on how to implement this study effectively. So those new sites are coming on sort of hitting the ground running. And so what we really have seen over the course of 2025 is markedly improved patient identification, markedly improved, MRD screening rates, and that is translated into a study enrollment.

Sam Semenko, Senior Biotech Analyst, Citi: Okay. And so that feeds into your expectation for the futility analysis, in the ’26. That remind me if I’m correct here. I believe it’s up to 12 or about 12 patients in in each arm will be included in that futility analysis?

Zach Roberts, Executive Vice President and CMO, Allogene: That’s correct.

Sam Semenko, Senior Biotech Analyst, Citi: Okay. And and what are the expectations there? Like, what would be good for you to pass that futility and to move and continue the study?

Zach Roberts, Executive Vice President and CMO, Allogene: Sure. Before I answer the question, let me just put a little bit of context there. So I I briefly mentioned a another frontline regimen that’s often used in The United States, especially for patients with newly diagnosed DLBCL, and that’s a regimen called Pola R CHIP. It’s based on a drug called Polatuzumab vedotin or Polivy. And the R CHOP is kind of a modified R CHOP.

So it’s essentially R CHOP plus. That regimen was the first new regimen to be approved in DLBCL in twenty five years about twenty years or so and since r was added to CHOP. And that study had about a 7% improvement in PFS, and that led to approval of of polar R CHIP. I think that illustrates very clearly that R CHOP is a very effective regimen, and it’s been really surprisingly difficult to beat it. So with that kind of a backdrop, how we think about this futility analysis coming up that you just mentioned is if we can see a 30% improvement in the efficacy assessment that we’re doing at that at that futility analysis, that would be a major advance in in the frontline outcomes for for these patients with newly diagnosed disease.

I will point out that the efficacy assessment that we’re using at that futility analysis is not the primary endpoint of the study, which is event free survival, but rather looking at the MRD conversion. So everybody that comes into alpha three comes in MRD positive as I pointed out earlier. And what we’re looking to see is whether that MRD positive becomes an MRD negative, after they’re enrolled in the study. And so what we’re looking for is a roughly thirty percent or better, delta between the MRD conversion in the two arms observation versus Semisel. We would consider that a a a pretty substantive improvement, especially given what historical, improvements have been even with improved regimens like polo hardship.

Sam Semenko, Senior Biotech Analyst, Citi: Got it. Okay. And so for for that readout, 30%. Right? And that that is based off the second line, Yescarta, Brionzi, sort of, complete response rate.

Is that correct?

Zach Roberts, Executive Vice President and CMO, Allogene: Yeah. So that’s another way sort

Sam Semenko, Senior Biotech Analyst, Citi: of a proxy?

Zach Roberts, Executive Vice President and CMO, Allogene: That’s another way to look at it. So if if, if these patients do progress, as we expect almost all of them will, the MRD positives, what what is their likely outcome in the second line? And even though, you know, we have kinda anchored to ZUMA seven and TRANSFORM, those are the the large randomized trials examining Yescarta and BRYANZI versus autologous transplants in the second line salvage regimen. The sad truth of the current status of relapsed DLBCL in The United States and globally is that the vast majority of patients don’t actually even get those therapies. They don’t even get CAR T.

They get something else that doesn’t work as well as CAR T or they get nothing at all. We actually see about a third of patients in The US based on recent claims data shown at ASH last year. About a third patients don’t even get second line at all. So there really is quite an opportunity to improve upon the outcomes in relapsed disease. And MRD positivity is absolutely a proxy for impending relapse.

Sam Semenko, Senior Biotech Analyst, Citi: Do we have any data that says people on this test that you’re using can come in and out of MRD positivity? I’m wondering if there’s any sort of, I guess, base level of potential false negative that we should expect in in the futility analysis.

Zach Roberts, Executive Vice President and CMO, Allogene: Yeah. So so that’s uncommon. No test is perfect, but we we do we expect that at a very low rate to occur. So, what happens if you’re MRD positive, you stay MRD positive. Now we we know from existing retrospective data that it’s not one hundred percent, and there are some patients who stay MRD positive for a long time, but but it takes a while for their their disease to recur.

And in in a very small number of patients, maybe twenty percent, eve even, you know, out three, four years, those patients have yet to recur even though they’ve stayed MRD positive. And in the case of of toggling back and forth, that is an extraordinarily uncommon event.

Sam Semenko, Senior Biotech Analyst, Citi: Okay. Great. Good to know. And then for going back to patient enrollment, I I I forget the phrase you used. Maybe it was markedly improved, in in the cadence, or success rate that you’re seeing.

I mean, does that give you confidence that you’re going to meet the, first half twenty six guidance for that futility analysis? Like, based on what you know right now, how confident are you?

Zach Roberts, Executive Vice President and CMO, Allogene: We are confident. I mean, and we are seeing good performance in enrollment. We’re bringing on more sites, every month. So, yes, that is a that is a solid guidance. I’m gonna switch my cameras here, hopefully get rid of the I don’t know what’s going on with this, blurriness here.

But let me just switch to my laptop, which might be a little bit better.

Sam Semenko, Senior Biotech Analyst, Citi: You’ve you flipped. You did one of those flips. That’s fun. Yep. I did a flip.

Okay. We’ll we’ll see we’ll see if that works better for you. Okay. Okay. So then, you know, let’s say you do pass this.

Let’s say you at least 30% MRD conversion. Right? You you continue the study. You have a plan interim EFS analysis and then a final EFS analysis. And and correct me if I’m wrong, but I I’m not sure if you’ve been able to give guidance for the timing of that.

Do you know when you might feel comfortable providing guidance on timing for those readouts?

Zach Roberts, Executive Vice President and CMO, Allogene: Yes. So you’re absolutely correct. We have not provided detailed guidance on the timing of the EFS analyses. There is an alpha spending interim analysis, and then there’s the primary analysis. And, we are deferring providing guidance until, we do the update with the futility results, in the first half of next year.

Got it.

Sam Semenko, Senior Biotech Analyst, Citi: So we’ll so we’ll know more then. And I assume that factors in the enrollment rates that that you’re having now and that you’re seeing, and and you’ll be able to guide towards that. Okay. Right. You know, just just thinking about how long it might take for the study to reach the number of events needed for what both the interim, but more importantly, I think the final EFS analysis.

How long does it take for a patient that comes back MRD positive to generally progress in the watch and wait arm for towards a second line, you know, or recurrence of their disease and where they would need second line therapy?

Zach Roberts, Executive Vice President and CMO, Allogene: Yes. So it’s variable. As you would expect, the best data that we have to look at on this comes from the recently published JCO manuscript from our partners, ForeSite Diagnostics, who is the group that is developing the test that we are using for this purpose. We’re it’s called Phase SEEK. And in that group of patients, overall, the median time to progression for an MRD positive patient at the end of treatment was less than three months.

So tends to be a fairly rapid event, but there of course it’s a Kaplan Meier and you do have some patients that take longer and so forth. So in any case, it happens quickly and already on the study we’ve had patients who have come back MRD positive. And then for, you know, this or that reason, didn’t, qualify for enrollment and randomization in alpha-three. And we’re already hearing back that some of these patients are progressing very quickly within a few short months. So the experience in alpha-three seems to be bearing out with that recently published dataset from the foresight group.

I’ll also add this is another reason why we think an off the shelf cell therapy is really the best tool in this context because you have to act very quickly, arguably much more quickly than you can act with an autologous product. The other limitation to an autologous product is that there may not be very many T cells that have recovered from the six cycles of R CHOP. And that also brings into question whether even a bispecific would work very well because there’s just not that many T cells to engage with your T cell engager. So really bringing in a product that is built from fresh T cells derived from healthy donor in a off the shelf rapid way is probably the best modality, to consolidate an MRD positive patient who in many cases may only have a few weeks before a clinical relapse.

Sam Semenko, Senior Biotech Analyst, Citi: Got it. Okay. And maybe let’s just talk about that. We talked a lot about the study design and the patient dynamics, but we haven’t really talked about SemiCell and the data you have supporting the efficacy here. Can you just walk through I know it’s in the later stages, but one of the things that I found interesting is that the patients with lower tumor burden seem to have better outcomes, and that seems to work really well or correlate quite nicely with what you likely would see in an MRD positive patient.

Can you just give a high level of that background for everyone?

Zach Roberts, Executive Vice President and CMO, Allogene: Sure. So Semacell got its start as cell therapies often do in patients with relapsed refractory disease. And in this case, of course, it was large B cell lymphoma. And we recently also published the results of that phase one in the Journal of Clinical Oncology. And, the highlights are that the efficacy seemed on par with what the autologous products, were delivering in a similar line of therapy.

And we saw about a fifty eight percent complete response rate in the Phase two regimen that we studied in that in that phase one. And as you point out, the less disease burden that you had at the time of your semiselle, and all these patients by these were not MRD positive patients, these were patients with with full on relapse. But there’s patients who have very bulky and aggressive relapses, and then there are patients who have, slow growing and small relapses. And so in any given population, you’re gonna have a a a spectrum. And so what we wanted to learn was whether we saw what was emerging in the autologous field that patients who have low disease burden when they receive their CAR T cell infusion, what are their efficacy outcomes?

And this has now been shown in several different settings in the autologous setting, several different therapies in the autologous setting that treating patients with low disease burden means that they have better outcomes, both safety and efficacy. So we looked at this and we looked at patients who had low disease burden and we sort of arbitrarily cut a line at a thousand millimeters squared of the sum of product diameters. And which is relatively small, but not very small, still visible on scan. And a 100% of those patients achieved a complete remission to SEMA cell. We also looked at another serological marker of disease aggressiveness and burden, which is lactate dehydrogenase, it’s a blood test.

And in the patients with low or normal lactate dehydrogenase, which is an marker of low disease burden and low disease aggressiveness, over eighty percent of those patients have achieved the CR. So this really does, number one, replicate the findings in autologous, but number two, and very significantly strongly indicates that if we take that even further into a patient whose only evidence of disease is this ultra sensitive blood based molecular ctDNA test, that we will be able to induce durable complete remissions in those patients even more effectively than in patients with relapsed refractory disease.

Sam Semenko, Senior Biotech Analyst, Citi: I have a question from another investor coming in. Did you ever check MRD status in patients from the phase one study after stem cell treatment?

Zach Roberts, Executive Vice President and CMO, Allogene: We so the short answer is we had a few samples that were appropriate. You you kind of have to plan for MRD testing. There’s like a special tube that you have to draw. So we did go back as we were talking about alpha three, and we looked at these results. And for, you know, a reasonable number of patients, not all, we did have some samples and we’re able to show that we were able to clear MRD in some of those cases.

Sam Semenko, Senior Biotech Analyst, Citi: Okay. Some of the cases. And was it did it correlate with a lower tumor burden cases?

Zach Roberts, Executive Vice President and CMO, Allogene: It was a mix. So we had some patients who had high disease burden, who did very, very well on that study. And you can go back and look at the swim lane plot from the JCO. We’ve got patients that are out past four years. The several of those patients did have the low disease burden, but there were also some patients with sort of more measurable disease.

Sam Semenko, Senior Biotech Analyst, Citi: Okay, interesting. And then, you know, back to the patient enrollment piece, I’m wondering if you could if there’s any framework you could share, I I doubt you could give specifics about the rate of the number of patients that are going into screening and the ones that make it through screening and then the ones that actually go into enrollment and, you know, remain in the study. Is there any framework on how you could talk about what that funnel looks like?

Zach Roberts, Executive Vice President and CMO, Allogene: Yeah. So, you know, I think the biggest piece of that funnel that we talked about came up a bit earlier, which is what the MRD positive rate is. And that sort of twenty percent ish range. So without getting into all the nitty gritty details here, one of the other things that we learned about this study its execution is that getting to patients early, in their treatment course actually is much better for their kind of likelihood of actually conducting MRD test and then coming into alpha three than waiting until the very last minute. Because often what patients will do when they’re when they’ve been given a diagnosis of LBCL, they’ve immediately been told by their doctor that they have a very good chance of being cured of this cancer, which is true.

That is what sort of clicks with folks. And then they go through their six cycles of R CHOP. They expect to be cured at the end because that’s what they’ve been told. They have a clean PET scan, and they’re like, okay. It’s time for me to take that cruise that I’ve booked and to reward myself for for going getting through this successfully.

To then come back and say, well, you know, we also have this other test, which will tell you tell us more accurately whether your disease is ready to come back. You know, patients would in the early days, like, what are you talking about, doc? This feels like a bait and switch. So we now talk to these patients quite a bit earlier and that comes with both pluses and minuses. On one hand, it, you know, we find these patients early, they get put into a logbook, we follow them through, we get the MRD test.

But what also happens is we don’t really know what’s going to happen with those patients when we talk to them after their first cycle or their second cycle. Some of those patients, about ten percent, will have primary refractory disease and will blow through, you know, the R CHOP and need to go on to second line AutoCAR. That patient obviously is not gonna go on to get MRD tested. Some patients will have toxicity to R CHOP, and they’ll decide they don’t want any more therapy or they’ll develop a new comorbidity. So we do see a sort of narrowing of that funnel even before we do get to MRD testing, and then we see about fifth of those patients coming back as MRD test positive.

Once we clear that MRD positivity, we’re dealing with a smaller pool of patients, but they tend to actually end up in the trial because the opportunity is so compelling. Even even for patients who are randomized ultimately to the observation arm, they are getting something more than they would be getting if they were just being cared for outside of a clinical trial. Namely, more frequent clinical visits, more frequent scans critically. Right? We’re scanning these patients more often because we really wanna see that disease come back sooner.

Or if it does, we want to act on it quickly. So we’re able to offer something comforting to these patients who are MRD positive, now expecting their disease come back any day if they come into health three.

Sam Semenko, Senior Biotech Analyst, Citi: Got it. Okay. That’s really helpful. And then so for the final EFS analysis, I’m gonna skip ahead all the way to that. Can you any framework you can say on the number of events that you’re expecting?

And and what, I guess, are the is the powering for a successful study on that readout?

Zach Roberts, Executive Vice President and CMO, Allogene: Yes. So we haven’t provided a lot of the details on the statistical design of the trial, and I won’t do so today. But suffice it to say that the bar is pretty low here. The study is designed treatment against observation. There’s a huge opportunity to improve upon outcomes, specifically in this ultra high risk patient population who is MRD positive.

And you can see that manifested in the overall study size, which is only 220 patients that are that need to be randomized.

Sam Semenko, Senior Biotech Analyst, Citi: Got it. And and so that’s a good segue because now I wanna talk about the commercial market. So let’s say I mean, well, for one, this is novel. It will take education and and physician engagement, you know, in a commercial launch. But I’m curious, you know, these sites that you have right now, they’re the ones that are gonna have experience with stem cell, you know, right out the bat.

So perhaps they are early adopters. You know, when you look at the population of of patients, total patients in The US, let’s just say, that are being treated at these sites, do you have a sense for what the opportunity is for the early adoption just solely in those sites? And then, you know, maybe you could talk about, you know, how it expands out to other sites that obviously will have interest in this if if approved.

Zach Roberts, Executive Vice President and CMO, Allogene: Yeah. So that’s a great question, Sam, and it gives me a chance to kinda talk about our commercial strategy in in kind of a a big picture sense. So I I worked at Kite as did Allogene’s CEO, and I was involved in the Zuma studies and led to the approval of Yescarta. And, you know, one thing as exciting and as transformative an experience for me as that was, one of the things that was sort of plainly obvious along the way was not very many patients are going to be able to get this treatment for any number of reasons. The insurance, but primarily it’s who your doctor is.

And eighty percent of patients in The United States don’t get treated at places like MD Anderson and Dana Farber and Moffett Cancer Center and and Fred Hutch. Right? They get treated at their local community oncology practice. And so if we were going to bring the promise of CAR T, the modality to everybody who is could benefit from it. We really needed to break the mold about how and where this therapy was given.

And so that was baked into our clinical strategy. We wanted to bring this trial not just to the MD Anderson’s and the Dana Farber’s and the and the Mass Generals. We wanted to bring it to community practices. And so if you look at our our site activation list currently on ct.gov, you’ll see about 50% of the currently open sites are community practices. Some of those, a nontrivial number of them, have no CAR T experience.

These are these are, local community practices that have, for many reasons, decided not to invest in the infrastructure needed to deliver a cellular therapy like autologous CAR T or bone marrow transplant. They are some of the largest proponents of alpha three because it’s for the first time giving them access to this curative modality for their patients. And they’re able to hang on to their patients. They don’t need to refer them out to a big academic center. So right out of the gate, at the time of approval, you’re absolutely right.

The centers that were part of the clinical trial will have a head start. But this is a very different launch strategy than any autologous therapy ever was or will be because it’s off the shelf. We shipped it overnight. It’s ready to thaw at the bedside and infuse. Most of our patients in the trial and actually a significant number of the patients even in the phase one relapse refractory are being fully treated as outpatients.

So we call this therapy in alpha-three, the seventh cycle of treatment for patients at high risk. And that really is resonating with a large fraction of the community oncologists out there. So this is a little bit of a hint of how we think our commercial strategy and commercial launch is gonna go. It’s gonna be a a lot less complicated or costly, as launching Yescarta was.

Sam Semenko, Senior Biotech Analyst, Citi: Got it. Okay. And not to push, but do do you have a sense for what that, percentage of patient coverage is within your sites?

Zach Roberts, Executive Vice President and CMO, Allogene: It’s it’s really hard to to guess. I mean, even with a fairly sizable number of US based sites, somewhere around 50 currently, know, that’s probably not capturing, you know, a huge coverage of patients. It’s just it’s not it’s really hard to achieve that with any clinical trial. You would need hundreds, if not thousands of sites open to really come close to capturing a large percentage of patients. But what matters is that this is a a therapy that is easily transferable to new sites.

Sam Semenko, Senior Biotech Analyst, Citi: Got it. Okay. And is there a difference in how you need to the community physicians versus the academic physicians that presumably have a lot of experience with the autologous CAR Ts?

Zach Roberts, Executive Vice President and CMO, Allogene: Yeah. So a 100%. Right? I mean, again, drawing on my own experience of the early days of autologous CAR, that, you know, that was a those those therapies were brand new. There was CRS.

There was neurotoxicity. All that stuff needed to be studied and learned and and mitigated kind of, you know, as we were going through the trial. Our product tends to be pretty well tolerated, and it’s very, very outpatient friendly. That said, we don’t wanna just sort of drop it off in the front door of these community practices and say, you know, go ahead and give this to your patients. So there’s a lot of training that goes in, not just how to handle the product itself, but, you know, what to expect after the after the drug is infused and what CRS looks like, what neurotoxicity looks like, even though, you know, with a low disease burden we don’t expect much of that in the trial.

We do want to make sure that patients are safe. One benefit that we’ve been able to draft on is that many of these practices are using bispecifics, which are approved in later lines. And they come with CRS, they come with neurotoxicity. So they become a little bit more comfortable dealing with drugs like tocilizumab and steroids and managing these patients. So, you know, the time was really right for us to bring this to those practices because they already had a functional knowledge of what a T cell toxicity looked like.

So some of our work is done, but we’re obviously being very careful, and we we wanna make sure that everything is being done safely.

Sam Semenko, Senior Biotech Analyst, Citi: Yeah. That’s a good point. Okay. So we spent a a good amount of our time on alpha three. I just wanna give an opportunity.

You know, what haven’t we touched on that you think is really important for everyone to understand?

Zach Roberts, Executive Vice President and CMO, Allogene: You know, I think this came through during our conversation. I’ll try to keep it brief. But, I mean, what we’re really doing here is is transforming care. And, that’s hard, but it’s always hard when you’re transforming care. And, we really are looking ahead to what, DLBCL management is going to look like in the in the very near future with MRD.

And and we expect that there will be additional trials that like alpha-three is such a compelling thought to be able to consolidate a low disease burden. So, you know, I would look at this opportunity as truly transformative and that comes not just for the care of patients, but also for allergy and the market opportunity that that we talked about at the beginning. This is really, a fairly sizable, and exciting opportunity for us as a company to really put, you know, put an impact here in this field.

Sam Semenko, Senior Biotech Analyst, Citi: Got it. Okay. Great to hear. So so and we’ll look forward to that, the futility analysis in in the first half. But but let’s talk about, you know, your your autoimmune asset, allo three two nine, which also has data expected in the first half.

So your your intro talked about it, dual CD nineteen, CD 70. I guess just walk us through the phase one basket study that you’ve initiated and the study design and how you’re handling lymphodepletion in this trial?

Zach Roberts, Executive Vice President and CMO, Allogene: Yeah. So, as I mentioned, this therapy has, through this dagger technology, built in lymphodepletion. And that was very well documented in our kidney cancer program, which also has the CD70 CAR. So for interested listeners, that presentation is available on our website. You can see some data around this dagger effect and why we think it’s so important.

So, when we were designing ALLO-three 29, we really did it for the group from the ground up, for patients with autoimmune disease. And we knew that one of the biggest barriers to widespread uptake of cell therapies for autoimmune patients is they don’t want chemo, and I don’t blame them. And their doctors don’t want to give chemo. So we had to have a plan for that. And it just didn’t feel right to us to take an asset that was designed for oncology and just bring it into autoimmune and hope we can do it without LD lymphodepletion.

So that’s where the CD19, CD70 idea was born. So as I mentioned, we we baked it into the study design. We actually have two parallel cell dose escalation arms as you do typically in a in a phase one, you dose escalate on the number of cells that you give. One with cytotoxin alone, so some lymphodepletion, but as I said, a dose that is commonly used in rheumatology patients. So it doesn’t include fludarabine.

It’s not a super high dose of cytotoxin. It’s something that they might be offered in their usual clinic. And then there’s a parallel arm with no lymphodepletion at all. No chemotherapy, nothing else. So we’re really excited about this.

Doctors are really excited about it. It is truly differentiated. We are starting to see now some other sponsors starting to, you know, play with no lymphodepletion. They don’t have the benefit of the dagger that we do though. And, you know, you mentioned the basket design.

This is a true basket study. We’ve got four indications, lupus, lupus nephritis, if you count that as a second, inflammatory myositis, and systemic sclerosis or scleroderma. And what makes this a very flexible design is we don’t have targets for individual indications. So our first dose cohort could be one of each or two of one and one of the other. And it gives a lot of flexibility to sites, some of which have more myositis patients, some of which have more lupus patients.

So there was a lot of flexibility baked in that the investigators have really liked. So we we think that this will help help us with enrollments in this competitive environment.

Sam Semenko, Senior Biotech Analyst, Citi: And how do you handle which arm patients get enrolled into? Is it just random or based on the site? And is that how it’s handled? And and you said they are enrolling in parallel. Correct?

Zach Roberts, Executive Vice President and CMO, Allogene: Yeah. They’re enrolling in parallel. I mean, they’re without getting into a lot of specifics, you know, it’s likely going to be roughly one here, one there. We’re not gonna be looking at an individual patient and making a decision based on their characteristics or their diagnosis. Are they more appropriate for this or that arm?

We really are gonna try to enroll them in parallel, more or less alternating that. That’s it’s not there’s not a formal randomization or anything like that.

Sam Semenko, Senior Biotech Analyst, Citi: Got it. Okay. And then so for the initial readout, what data should Should we get data from both of these lymphodepletion cohorts?

Zach Roberts, Executive Vice President and CMO, Allogene: That is that is the goal. We expect in the first half of next year to have data from both of these arms, certainly in the early dose cohorts. This is a dose escalation study. And, you know, we’re expecting some biomarker data looking at, you know, the the change in the number of b cells and t cells in the periphery. Maybe there are surface phenotype that has been reported by other CAR T, datasets, and then some early safety and efficacy as well.

Sam Semenko, Senior Biotech Analyst, Citi: Okay. Excellent. And and I guess, you know, once we see that, we’ll have a better feel for this. But you sort of alluded to some other companies taking away lymphodepletion or reducing it. And, obviously, you have the Dagger technology.

But is there any difference in how you handle the reduced lymphodepletion versus some of the others that are trying it in the field? Or, like, is your cytotoxin level less or the same? I’m just curious if there any other differentiating aspects in the design.

Zach Roberts, Executive Vice President and CMO, Allogene: Yeah. So, I mean, again, I I I I’ll say that, you know, we’re to be to be perfectly blunt, I mean, we we came to this a little bit later than some of the other sponsors. And we had to be quite disciplined internally to not just rush into it with, say, SemiCell or whatever. Right? And we really wanted to focused and goal directed, but really be quite systematic about what does the right product design look like.

So we spent a little bit of time with that. You know, we brought this product forward. And then with the study design, the same exact thing. Like, let’s design something that is fit for purpose. So I’ll give you one example.

I mean, the Cytoxan dose that we’re using is the standard dose that is given to rheumatology patients of a drug that is given to rheumatology patients. It’s not kind of like it or it’s like a CAR T dose, but we’re giving it to a rheumatologist. It is the dose that these patients get. So and we started with that in mind. So again, this isn’t let’s iterate, let’s hope for the best and and, you know, work our way into something that suits rheumatology.

Let’s start with something that really will resonate with that population and that group of doctors.

Sam Semenko, Senior Biotech Analyst, Citi: Got it. And is there your expectation that the CD 70 piece of the equation, how necessary is that for when you remove lymphodepletion? I’m asking this because you mentioned there are a couple other sort of endeavors out there for other assets. You know, what are your expectations for how differentiated your data could be with c d 70 and reduced or no lymphodepletion versus other assets that don’t have c d 70 and reduced and no lymphodepletion?

Zach Roberts, Executive Vice President and CMO, Allogene: Yeah. So, I mean, I wanna make sure that I put this out. We’re speculating here, right, because we ultimately, we have to run the study. And and, you know, even once you have data, cross trial comparisons are always tricky. So

Sam Semenko, Senior Biotech Analyst, Citi: Sure.

Zach Roberts, Executive Vice President and CMO, Allogene: But knowing what we know about the dagger, we think we have a very good shot at getting robust cell expansion with low to no lymphodepletion. And I’ll even say without giving away too many details that as we’ve been preparing a publication for the CD90 the CD70 kidney cancer program to us, you know, on the heels of the ASCO presentation that I mentioned earlier, we performed some additional translational analyses, which has further built our confidence that this dagger will propel these cells in the autoimmune patients to divide even in the absence of significant lymphodepletion. So based on those actual translational results as well as developing preclinical results, we think we have a really good chance of doing this. And I don’t also want to give short shrift to the fact that CD 70 is likely an important molecule in autoimmunity by itself to say nothing of the dagger effect in cell expansion. We know that patients with treatment refractory and severe lupus and other inflammatory disorders have higher frequencies of CD 70 expressing T cells in their bloodstream.

We know that CD 70 is important on B cells in these patients. So having the dual targeting of a relevant molecule on activated lymphocytes will give us additional benefit on the efficacy side we expect. And while, you know, some may say that, hey, look, CD 19 looks like it might be enough. I’m not sure we know that yet. I mean, you know, we we have heard that some patients are progressing and certainly we’re seeing in vivo patients, you know, not having as deeper response as patients with autologous CAR.

So it’s quite likely that you might need to tackle the T cells on some level as well. Even within the rheumatology disorders, that is probably going to be more significant as we expand into other diseases, neurology, endocrinology, gastroenterology, where classically there is a larger role for the T cells in those in that pathology. So a c d nineteen targeting b cell may not have much to offer in that case, whereas we expect to expand very aggressively outside of rheumatology once we’ve established proof of concept there.

Sam Semenko, Senior Biotech Analyst, Citi: Yeah. I know when you start to add in other therapeutic areas outside of rheumatology, it gets quite a quite a large well, you multiply the TAM quite a quite a lot. Okay. So so that was very helpful. So I guess, you know, I want to just one of my last questions is how Allogene is thinking about their capital allocation.

You have two, really interesting assets, one late stage, one much earlier stage. I think $3.01 6 is is on pause for future clinical development. But how how are you thinking about it going forward? And just remind us on your cash runway.

Zach Roberts, Executive Vice President and CMO, Allogene: Yeah. So we have cash runway into the 2027. And, you know, from a company prioritization perspective, our sort of highest probability of technical success, I think, currently sits with ALPHA3. The design of that study randomized, FDA discussed and agreed design as a pivotal design. Randomizing against observation is not something that comes around all that often in oncology.

We know it’s an active therapy. We have a very sound clinical and commercial strategy there. So accordingly, most of our resources, you know, time and dollars are being spent on ALPHA-three. That said, you know, we are very excited about three twenty nine and are looking for ways to move very aggressively with the expansion of that program upon achievement of proof of concept that we expect to share in the first half. And then 03/16, like, this data is potentially transformative.

I mean, we’ve never seen and when I say we, I mean as a field. We have never seen solid tumor data like what we presented in the kidney cancer trial at ASCO as an oral presentation in the main GU session. That has never been shown with an off the shelf CAR T therapy. We think that data is tremendously exciting. We are eager to move that program forward.

As you pointed out, we’re not internally doing that right now, but we are you know, having partnership conversations on this program and we’re hoping to find a way to move that forward, you know, in the future.

Sam Semenko, Senior Biotech Analyst, Citi: Got it. Thank you, Zach, for that. I guess, you know, that’s the end of my list of questions. I just want to turn it back to you for general closing remarks you might have.

Zach Roberts, Executive Vice President and CMO, Allogene: Sure. Sam, thank you so much for this opportunity. It’s really wonderful for us to be able to talk with your investors here. We think Allogene is a great opportunity. We’ve got a lot of very exciting programs, including a pivotal program up and running.

It’s a very, very exciting time in the field of cell therapy. I know it’s been kind of a tough few years for the sector, but with companies like ours, new technologies like MRD and other things coming to the fore, I really feel like we’ve got a brewing renaissance here. And we just the next few months are going to be very telling for for the field and for algae. And so it’s wonderful to be able to share that with your with your listeners.

Sam Semenko, Senior Biotech Analyst, Citi: Yes. Well, I’m looking forward to all of the data in the first half. And thank you, Zach, for being here today. It’s been a wonderful conversation. Very much enjoyed it.

Zach Roberts, Executive Vice President and CMO, Allogene: Thanks, Sam.

Sam Semenko, Senior Biotech Analyst, Citi: Okay. Alright. Well, with that operator, we can go ahead and close the call.

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