Excellent. Good morning and welcome, everyone. Welcome to the Citizens JMP Hematology and Oncology Summit. It is my pleasure to introduce Allogene Therapeutics and present for the company's CEO, President and Founder, David Chang. David, welcome. Thank you for joining us. Really appreciate the time.
Thank you for having us, and I hope everybody had a nice Thanksgiving weekend.
Yeah, no, terrific. So, you know, I never know exactly who's on the call, whether they've heard about the Allogene story or not. And so for, you know, those rare listeners who might not be familiar, could you take maybe two to four minutes to just tell us what the company's all about and a little overview of the pipeline?
Yeah. So, you know, first of all, Allogene, I mean, you know, we are, you know, focusing on advancing Allogeneic CAR T therapy, which we believe is the only way to democratize cell therapy and make it available to a wider patient population who are in need of the therapy. And, you know, from day one, we have been focusing on hematologic indications. And, you know, as you know, we advanced our pipeline, we also moved programming to the solid tumor. And more recently, with all the excitement of using cell therapy and autoimmune indications, we also have a very differentiated program that is slated for the IND filing first quarter of next year. Starting with the hematologic malignancy, the lead program is cema-cel, which we are currently conducting a pivotal study, ALPHA3 study in large B-cell lymphoma indication.
The target patient population that we are going after is very unique in that there are no approved products, you know, for that indication. As well as, to our knowledge, there's no other competitive clinical trials that's ongoing. It is in the early allogeneic setting. Essentially, this study is also named as an ALPHA3 frontline consolidation study. So what that means is that when a patient undergoes the treatment in the frontline setting, some patients, their needs are fully addressed with six cycles of R-CHOP or equivalent chemoimmunotherapy. However, about 30% of the patients will have a disease relapse after completing the R-CHOP treatment. What we are doing in this ALPHA3 study is combining highly effective treatment, that cema-cel, together with the recent advances in the detection of MRD using circulating DNA so that we can identify patients who are destined to relapse after completing the R-CHOP treatment.
So that's why we coined this study as a frontline consolidation study. So from the patient perspective, they would complete the R-CHOP. If they are MRD positive, they are eligible for ALPHA3 study where they can receive a single cycle of cema-cel, hence the name frontline consolidation. We also have a CD70 program ALLO-316, which is, you know, can go into many different hematologic indications that's in the IND enabling phase. We have more pipeline that we have disclosed in the solid tumor starting with a CD70. This is ALLO-316 that we are currently studying in the renal cell cancer. We recently updated the data coming from the TRAVERSE study in renal cell cancer where we have disclosed a confirmed response rate of 33% at the dose, cell dose, as well as lymphodepletion regimen that we plan to further evaluate.
We are continuing to enroll additional patients at this phase 1b extension, and the data will be updated mid-2025. CD70 ALLO-316 also has potential for other solid tumors. In the pipeline, we have ALLO-213, which is targeting DLL3 for small cell lung cancer, as well as, you know, other tumor types. ALLO-182, which is targeting Claudin 18.2 for gastric and pancreatic cancer. These programs are in IND-enabling stage. Another program that we are really excited about is ALLO-329. This is taking cell therapy to outside hematology oncology into the autoimmune indications. This is a very differentiated approach of addressing the autoimmune causing B cells and T cells. The target is CD19, CD70. So this is actually dual CAR that will go after rheumatologic disorders as an IND, first IND.
And we plan to file the IND in the first quarter of 2025, potentially start the study mid-year, leading to proof of concept data generation by the year end 2025. So across hematology cancers, solid tumors, and autoimmune indications, we have very robust, and I would also say very differentiated from the clinical trial design and selection of indication perspective that would apply to the cema-cel program of CD19 to, you know, solid tumor where very few programs, CAR T programs have shown any kind of efficacy at the level that ALLO-316 has shown. And also going into the autoimmune indication with a, you know, product that has a very differentiated mechanism of action. So the focus of the company is really, you know, differentiation and innovation.
Supporting all this activity is our own manufacturing facility where we can not only do the process development and analytic assay development, but also manufacture the product for clinical studies, as well as if the study is successful, potentially launching the product from the manufacturing facility that we control.
Excellent. Thank you very much for that overview. Let's jump right into it. You know, to us, the ALPHA3 trial is, I mean, it's quite unique. I think you guys very shrewdly, you know, are navigating this LBCL space. As you mentioned in your remarks, there's not much competition on what is, you know, presumably a seventh round, right, in the frontline setting. You walked us through a little bit of the rationale, you know, at least by mentioning that 30%, you know, will undergo a disease relapse. I assume these are the patients that have MRD positivity. Can you maybe just take us through a little bit of, you know, the, you know, what it is to be MRD negative in LBCL?
Kind of what are the thresholds that you might be looking at, especially with this new assay that you have and how you expect this to, you know, to help you in the enrollment of this study?
Yes. I mean, all very important questions. So let's start with the assay itself, because this is a very novel approach of detecting the MRD. It is a circulating DNA, you know, based assay. And the readout using the computer algorithm is essentially whether a person is MRD positive or MRD negative. And, you know, the data suggests that, you know, between 20%-30% of the patients will be MRD positive at the end of six cycles of R-CHOP. And when you look at the outcome of those patients, the ones who are MRD negative remain progression-free, survival-free, meaning that they do not have the recurrence of the disease. Whereas if you are MRD positive, so this would represent, let's say, about 25% of the patients, they will have a disease relapse. You know, more than 85% of them will have a disease relapse within the first two years.
The median time to having a disease relapse is about six months or less after completion of the R-CHOP treatment. What we are doing is letting the patients, most of them are treated in the community-based cancer centers, complete the six cycles of R-CHOP and then come in at that point with the MRD testing. If you are MRD positive, then you are eligible to enroll into the ALPHA3 study. In the beginning of this study, and this study, by the way, you know, is ongoing, we are randomizing patients one to one to one into observation. This is really following the patients for disease recurrence, which is the current standard of care. Two additional arms, we are testing two different lymphodepletion regimen, FCA and FC.
We intend to make a decision on which lymphodepletion that we choose to continue on the study in the middle of next year. Once that lymphodepletion selection has been made, the study will continue on as a one to one randomization with the chosen lymphodepletion followed by a single cycle of cema-cel or the observation. Primary endpoint is event-free survival, and the key secondary endpoint includes progression-free survival and overall survival. We intend to enroll approximately 240 patients into this study. If all goes well, the study will be completed by mid-2026, leading to the primary analysis of the endpoint by the year end 2026.
Excellent. Can we talk a little bit about, you know, maybe what your expectations are for an MRD positive conversion rate? You know, do you ever worry that, or "worry" is the wrong word, but do you ever think about maybe since these patients are already coming, they've responded, that there might not be enough cells for cema-cel to actually encounter to, you know, even expand? And I guess kind of related to all that, what's the data from the ALPHA2 study that really helps you kind of hone in your calculations, if you will, for, you know, how cema-cel might be able to convert MRD positive to MRD negative?
Yeah, all great questions. I mean, first of all, MRD conversion you're talking about is, you know, when MRD positive patients receive cema-cel, how many of them will become MRD negative? I think that's a very important question because in the second line setting where MRD conversion using the same assay that we will be using in the ALPHA3 study has been looked at, the study has shown that those people who are MRD positive, and obviously these are patients who have visible, you know, recurrent disease, when they become MRD negative, these are the patients who will have a durable response. So converting MRD positive to MRD negativity is a very important aspect. It is not approved in a clinical endpoint, so we will not be using it as a primary endpoint, but we will be using MRD conversion to make the selection of lymphodepletion mid-2025.
In terms of, you know, our expectation, I think it starts from what we have seen in our relapsed/refractory study. We're using cema-cel where we have studied many patients. In the data set that we have previously released, a single cycle of cema-cel in the relapsed/refractory setting will provide a response rate of approximately 50% CR. Many of them will, you know, continue to have a durable CR afterwards, and, you know, your question about, well, these patients don't really have disease, you know, volume, you know, will the CAR T, you know, work? That has been answered in many different settings of the autologous CAR T as well as our own study. People, patients with a low volume disease generally do better with the CAR T therapy, both in terms of safety as well as efficacy.
That has been shown repeatedly both in the clinical study as well as in the, you know, in the real-world setting of all the autologous CAR T therapy. Similar data is coming up in an analysis of our own data, which we will present at some point. In terms of MRD conversion in our own study, we have not presented, but we have analyzed a limited number of patients. From that perspective, it doesn't give us any concerns about using MRD conversion as the key endpoint of making the lymphodepletion selection in 2025.
Excellent. Can you, you know, the majority of the patients are coming from the community setting. Can you talk a little bit about kind of how enrollment is going? You know, I imagine that the majority of the community centers don't have prior CAR T experience, but maybe they do, or maybe they have really good relationships with CAR T centers. Can you talk a little bit about, you know, the process of getting these community centers on board and how enthusiastic or not enthusiastic they might be?
First of all, you know, when we were selecting clinical sites, and at that point, we were approaching both, you know, academic centers as well as community-based cancer networks, the receptivity from the community-based cancer networks was extremely high. They were unwilling to build the infrastructure necessary to bring the autologous CAR T. But with the allogeneic CAR T, that takes away with all the logistical challenges. It made the proposition much easier. And, you know, they see ALPHA3 study as an opportunity to bring the CAR T for their patients who are treated in the community-based cancer centers. Why going after community-based cancer centers is so important is that's where the patients, majority of the, you know, large B-cell lymphoma patients cared for, upwards about 80%.
By treating patients in the community-based cancer centers, that's the right thing, going after the patients who are in need of the treatment at their home or near home, rather than requiring those patients to be referred to cell therapy centers, which can be some distance away from their primary residence.
Got it.
In terms of, you know, site activation and the study so far, the ALPHA3 study was initiated towards the end of June this year. And we are targeting approximately 50, you know, academic or community-based cancer centers in the U.S. And so far, the site activation has been going extremely well. We have more than, way more than 50% of the sites that are already activated. And screening for the MRD, as well as enrollment, is ongoing. However, as previously communicated, we will not be providing a play-by-play updates on how the study is going.
Gotcha. You mentioned, you know, that I guess the next big thing is, of course, the readout, if you will, right, for which lymphodepletion regimen you're going to be selecting by the middle of next year. There was some data, you know, that was announced at SITC, granted in solid tumors, right, RCC. Is there any sort of read-through that you might have between kind of the lymphodepleting regimens that were used there and whether there might be a read-through into this ALPHA3 study? Or do you kind of feel, you know, different indications we really need to run the test, you know, on this population?
Yeah. I mean, there are some positive read-through, I mean, without a question. But I think it is important that, you know, each indication needs to be, you know, sort of looked at separately, and especially in the MRD positive setting, which is lowest disease volume. But we certainly expect the overall, you know, CAR T treatment will be, you know, very well tolerated. And also, you know, for that reason, not only are we testing FCA lymphodepletion regimen, which is the regimen that we have been using in the relapse refractory setting, but also testing FC, much simpler lymphodepletion, because this is a different disease setting than the relapse refractory setting that we have been studying.
Gotcha. One final question just with this program before switching to 329, regarding the interim analysis that's coming up, right? You have interim data readouts, I guess the main one middle of next year. Is it just going to be an announcement to investors in terms of which lymphodepleting regimen you're moving forward with? Or because you've evaluated, you know, both in some patients, will you talk and allow us to kind of see and think about what MRD conversion rates might be or any other information that might come up during that interim?
Yeah, great question. I wish we can communicate the details of the interim analysis, but we expect at the time of lymphodepletion selection, the study will be still ongoing, and we need to maintain the clinical equipoise of the study, so for that reason, the announcement will be relatively simple about which lymphodepletion has been selected, but in terms of, you know, what we plan to do at that time is, you know, first of all, you know, compare the MRD conversion between the observation and treatment arm. This will be sort of equivalent to the, you know, futility analysis. Obviously, we want to see more MRD conversion happening with a cema-cel treatment, and essentially, nobody, you know, having MRD conversion with observation alone, so there will be, you know, one hidden information when we announce the lymphodepletion selection, so essentially, you know, the study is working.
In that setting, we're going with one of the two chosen lymphodepletion regimen. You know, third information that will have, you know, that will be included in that announcement is how many patient data we have looked at to make the determination of the lymphodepletion. That will certainly give some insight into the cadence of the enrollment and whether the study will actually complete the enrollment by the first half of 2026.
Excellent. Thank you for that. In the last kind of couple of minutes that we have, would love to, you know, switch gears to ALLO-329. You know, it's a very exciting space. A lot of investors are focused on it. We've seen some interest dwindle a little bit compared to the, you know, the significant amount of excitement we saw, let's just say, earlier this year. Would love for you to just talk a little bit about not just the rationale for 329, but what sets 329 apart from the rest of the players in the field.
Yeah, I think the emerging data with the CAR T in the autoimmune space is, you know, really, you know, the paradigm-shifting approach to how we can manage the patient with autoimmune. Rather than offering chronic treatment to control the disease, CAR T is offering one-time treatment that can reset the immune system and offer, you know, prolonged, you know, remission, drug-free remission to the patient. And this is really, you know, something that nobody thought would be possible until the data was presented with autologous CD19 CAR T. What we're doing with the ALLO-329 is sort of taking into the, you know, the next stage of, you know, what we can do with the CAR T. Not only is the product designed to deplete the B cells, it is also designed to deplete the activated, you know, T cells and other immune cells that contribute to the autoimmunity.
It really addresses the fundamental defect in the autoimmune disorders. Another thing that we are really trying to do with this program is reduce the lymphodepleting, you know, requirement, lymphodepletion requirement before CAR T can be given. Why is that important? When we have to use the FC lymphodepletion, that's going to limit the use of the product to most likely patients with a severe disease. However, if the lymphodepletion requirement is lessened, the treatment can now, you know, move into the patients with the moderate disease or even to the earlier setting. We are really thinking about the, you know, the target product profile as a key aspect of how we design the ALLO-329. That's why this program, one, is advancing as a CD19, CD70 dual CAR.
And also along the way, we changed the engineering, you know, rather than using lentiviruses to transduce the CAR T cells, we're using the site-specific integration to simplify and improve the manufacturing, so you know, everything so far is looking very good, and what is shown on the slide is preclinical data that we recently presented at ACR Convergence meeting about a month ago, which shows that in a humanized, so these are the, you know, the mice that have been reconstituted with the CD34-positive, you know, hematopoietic stem cells from human, how the treatment of 329 can transiently deplete, but allow the B cells to come back and also expand well, which is shown on the right side.
It's preclinical data, but so far, everything is looking so beautiful about how 329 behaves in preclinical models, as well as all the manufacturing work that we have done in preparation of the IND, which we plan to file first quarter of next year.
What will be the first indications to be assessed in this phase one? And do you plan on enrolling multiple indications at the same time? Or is this more of like a sequential plan as you expand into AID?
Yeah, so, you know, we are sort of, you know, deferring the details of the study design, as well as indications that we are going after, you know, when the IND is cleared. But I would say that much of the focus of the, you know, our development team is, you know, how to go broadly as quickly as possible.
Got it. Maybe in the last minute, we have, you know, I know you have enough cash that takes you out to the second half of 2026, which is a great enviable cash position to have. These are the milestones that we have. You know, what would you highlight, maybe just in a minute, to the investors who are listening in, the key milestones for the next sort of 6 to 12 months?
Yeah, first of all, I would say, you know, within our cash runway, which extends to the, you know, second half of 2026, you know, we have multiple, you know, catalysts, you know, across all three programs. For the CD19, you're talking about the lymphodepletion selection in mid-2025, very important. Also, you know, probably more striking is in, you know, first half of 2026, we will complete the enrollment and have the, you know, the interim, you know, analysis of the primary endpoint, which can potentially reach the statistical significance. In the second half is the primary data readout from the ALPHA3 study. CD70, as well as ALLO-329 IND program that we just spoke about, it also has a very catalyst-rich 2025.
You know, the CD70 program in solid tumor, we plan to update the efficacy data as well as the safety findings from the phase 1b study mid-2025. And ALLO-329 autoimmune program is really, you know, where we take the program into the clinical setting and try to generate the initial proof of concept by year-end 2025. So next year, you know, is a busy year for Allogene, and hopefully, you know, all will go well as we are hoping.
Excellent. David, thank you very much for your time. As always, very much appreciated.
Thanks for having me on your conference. As usual, you know, very insightful questions, which I really appreciate.
Thank you.