All right, we'll go ahead and get started. Thanks, everyone. Welcome to our first session of the 2024 Healthcare Conference. My name is Ben Burnett, biotech analyst at Stifel. Pleased to be here with David Chang, CEO and co-founder of Allogene. Thank you for being here. Ben, thanks for having us here. Maybe start by giving us just a high-level overview of Allogene, and we'll get into it. Allogene specializes in allogeneic CAR T therapy. We have been working on this, both on the platform side as well as advancing targets into different indications. Right now, we have three key programs. One in hematology. This is a cema-cel program that's going into the first-line consolidation. Very innovative study design that has gotten very positive receptivity from the clinicians and the investigators. We also have a very innovative, and this is differentiation through the mechanism of action program that's going into the autoimmune indications. I know that there has been a lot of excitement about using CAR T as a means to deplete lymphocytes to treat autoimmune diseases coming out of the ACR meeting that happened over the weekend. And we intend to advance ALLO-329 into the autoimmune indications. And our plan is to file the IND in the first quarter of 2025. And then the third program is one that we are continuing to advance in the solid tumor indications. This is ALLO-316 that we have recently reported efficacy data out of 26 patients who are treated in renal cell carcinoma. Wonderful. Let's start with cema-cel and ALPHA3. So this is the first study that we're aware of sort of leveraging MRD positivity as sort of a clinical action point. That sort of paradigm shifting, maybe talk about what has been the physician sort of feedback to that type of design. I would say this is one of the very rare studies. I mean, I have had maybe one or two experiences like this where the physician receptivity, both the investigators as well as physicians in general who specialize in lymphoma, has been extremely high. And I would say that comes from three different angles. One is the fact that we are selecting patients based on the MRD status. And the purpose of that is to provide treatment only to those who need the treatment. And this is extremely well embraced by the physicians. And the second thing is that it's really coming from people who recognize the CAR T therapy and where it works well and where it needs some improvement. Historically, since the data from the autologous CAR T has come out, it has been known for some time that patients with low volume disease do extremely well, both from the efficacy and the safety, and treating MRD positive patients would be considered as probably the lowest volume that one can consider, so based on the data that we have presented with cema-cel in the relapse refractory setting and this notion that in the MRD positive setting, the efficacy and safety would be much better. At least that's what the physicians are saying. I mean, that's also creating a lot of excitement, and then last is we have targeted community-based cancer centers because that's where most of the 39 patients are being treated. The responses that we are getting from the community-based cancer center physicians is they like the logistical easiness of administering allogeneic CAR T and the fact that it will be available on demand, and this is they see as an opportunity to bring the CAR T therapy to their clinics. So that's exactly where I wanted to go next. So some of these frontline patients are treated by a community oncologist. So what has been, it sounds like you're getting some good feedback from community oncologists, but what has been sort of the participation by community oncologists in the ALPHA3 study? Yeah, speak to that. Yeah, so at this point, we are continuing to activate the clinical sites. And so far, we have more than half the targeted clinical sites already been activated. And the majority of them are community-based cancer centers. And at the end of the total target site activation, we expect about 40, maybe 50% of the sites will be the community-based cancer centers. And one thing to really sort of think about is the practice pattern. Most frontline patients, and frankly, available data would suggest that 80% of the large B-cell lymphoma patients are taken care of at the community cancer centers. And when you think about in the frontline setting, the urgency to treat those patients who are recently diagnosed with lymphoma, which is where the discussion and the treatment happens in the community cancer centers. Taking CAR T study to the community cancer centers, we believe, is very important. That really follows the flow of the practice pattern, especially when we let the patients complete the six cycles of R-CHOP or equivalent, and then come in at that point with the patient selection based on MRD, and then offering one cycle of cema-cel to improve the cure rate. Yeah. Okay. Fantastic. And I guess maybe just speaking to the kind of paced enrollment in ALPHA3 that you're seeing, anything you can kind of say about that and sort of what is the clinical trial footprint that you ultimately want to have there? Yeah. So as I said, we've been extremely pleased with the speed of site activation. And also along with that, we have tested a number of patients for MRD status. And we haven't provided any details of enrollment, but actually, we will not do that. We're not going to do a play-by-play updates on how the cema-cel study is ongoing. But from the site activation, which really, I would say, reflects the excitement that we have sensed from the investigator. I mean, usually when investigators say they are excited about the study, site activation moves a little bit better. And we are definitely seeing that. And we are seeing a lot of activities in the MRD screening. Going back to the concept that this is paradigm changing where you're inducing some clinical action based on MRD positivity, what does this stop a physician from just kind of crowning MRD positivity as being, okay, you've now relapsed, you're now a second-line patient? Yeah, I think probably the better question is, is there anything that would allow physicians to treat the patients based on MRD status after the completion of frontline treatment? The answer is no. That is not the current standard of care. And the current standard of care, especially after the patients, when patients complete the frontline treatment, is watch and wait, following them with the periodic scans. That is the current standard of care. And the preliminary data that drove us to do this study, which is really coming from retrospective analysis of what happens to the frontline patients based on the MRD status, the data is very compelling. But we still have to show that in a clinical study that intervening based on the MRD status would provide long-term benefit to those patients. Great. Okay. So ALPHA3, there's a couple of events coming up. So you'll select a lymphodepletion regimen next year, interim analysis after that. Could either of these events precipitate a change to sort of your target enrollment or your powering? I mean, the study design of ALPHA3, there's a lot of flexibility around it. Certainly, changing the sample size, which can be implemented, especially if the data is reviewed by the independent data monitoring committee, we have that opportunity. But having said that, this study is extremely well-powered, especially with respect to the key endpoints. The primary endpoint that we are using is event-free survival, and I would say the study is very well-powered. Okay. Great. And if all goes as planned, what is kind of timeframe for us, what is the commercial opportunities you see in the frontline setting? Yeah. So we estimate in the U.S. and key European EU5 countries, the total number of patients who are treated for the frontline treatment will be around 65,000 patients. Not everybody will be eligible for the cema-cel frontline consolidation approach. The majority of the frontline patients will be cured from the R-CHOP. But there are about 25% to 30% of the patients who, despite having a good initial response, they relapse within the first 24 months. That is the target patient population. So if you do the math and also layer in the penetration of the MRD testing in this patient population, we come up with an estimated number of close to 15,000 patients who could be eligible for the consolidation approach. And I would say that is a very attractive market commercial opportunity. Very cool. Maybe also if you could talk about your manufacturing capabilities with Cell Forge 1, I guess the question is, are you seeing any difference in sort of apheresis starting material in ALPHA3, just given the different setting relative to your later line studies? Yeah. The manufacturing process that we are using for the ALPHA3 consolidation study is the same manufacturing process that we have been using in the relapse recurrent setting. In the relapse recurrent setting, we have shown very respectable response rate, complete remission rate that's between 50%-66%, depending on how you cut the data. Many of these responses were very durable. We already know that the manufacturing process that we are using is very good. We will be moving into the frontline consolidation, essentially using the same approach. Having said that, we always try to make minor improvement. Some of the improvement that we have introduced is related to formulation and filling process. At the beginning, we were manually filling the vials, but now we are using automated fillers, which really improves the capacity or how many vials that we can fill after the completion of the production. Okay. Great. So we are coming off the heels of a rheumatology meeting, ACR, and I think you just presented or put out a press release about ALLO-329. Maybe just talk about this product. And I guess in your mind, what sets it apart from competitor assets? First of all, let's talk about what's happening in the rheumatology area. I mean, what the data that have been presented across different companies using CAR T, and there were some T-cell engager data as well. This is really getting the excitement of all the rheumatologists. I mean, we were just talking before the meeting, you were there, and how the presentations were standing room only when any CAR T data was being presented. I think that really reflects the potential that the physicians are seeing with a deep B-cell depletion approach in treating autoimmune indications. Autoimmune indications, now we're talking about lupus and systemic sclerosis. When you think about the different indications where the underlying mechanism is dysfunctional immunity, you're talking about many different indications in rheumatology, also neurology, hematology, and even nephrology. It is estimated that current drug sales in autoimmune indication is close to $70 billion. And it's projected to grow to about $125 billion in the next five to 10 years. This is a great opportunity, and the fact that through B-cell depletion, you can potentially control the autoimmune disorders for a prolonged period of time and only with a one-time treatment. I mean, I think this is a very exciting proposition. Excellent. Yeah. So back to your question about what we are doing. So we are advancing ALLO-329. This is differentiated from the mechanism of action perspective. We are advancing CD19, CD70 dual CAR that we transduce into the T-cells using site-specific integration. And CD19 CAR is expected to induce deep B-cell depletion. And CD70 CAR is expected to deplete CD70 positive T-cells. And this is a very attractive proposition because included in the CD70 positive T-cells are those dysfunctional autoimmune cells that contribute to autoimmunity. So we are able to go after the fundamental biology of the autoimmunity, not just the B-cells, but the T-cells as well. The second part of the CD70 positive activated T-cells are, we have learned, and there's a lot of literature that are being published, in the allogeneic cell therapy setting, the recipient, the patient's T-cells that are CD70 positive are the main contributor of the rejection of the allogeneic CAR T-cells. Being able to go after CD70 positive T-cells allows ALLO-329 to overcome the immune rejection that can shorten the survival of allogeneic CAR T-cells. Frankly, some of the data that we have generated with a different CD70 CAR program, this is ALLO-316, demonstrates that despite being allogeneic, using a standard lymphodepletion, we get great cell expansion as well as prolonged persistence. So CD70, the Dagger technology, it's not just about evading Allo rejection. That's part of it. But it's also about going after other disease cells other than just CD19. Precisely. Yeah. And I guess maybe talk about the tox profile. We're starting to see some toxicity profiles emerge from various autologous programs. I think pretty soon we're about to learn about some of the other allogeneic programs. But what is the toxicity profile that you think would be appropriate for these various autoimmune indications? Yeah. So in a toxicity profile, I always think about it in terms of benefit-risk. So in patients with a severe disease that do not have any alternative treatment options, those patients are willing to accept more toxicity than patients who have many other options. Some of the reported toxicities or adverse events with a CAR T or deep B-cell depletion is cytopenia. And some of that is coming from the so-called conditioning chemotherapy or lymphodepleting chemotherapy that is given before the CAR T therapy. And then there's also, as expected, when you let the CAR T-cells expand, you see some cytokine release syndrome. And in rare cases, there has been some reports of the so-called ICANS for the neurotoxicity. But overall, the adverse event profile that we are seeing in patients with autoimmune disorders for the same CAR construct that has been tested in the patients with leukemia or lymphoma, I would say this is generally much milder than patients with leukemia or lymphoma. And the view is that in the autoimmune setting, the target is B-cells. And the diseased cells that we are trying to eliminate, it's relatively low volume. And just as I've said in the case of cema-cel, when the disease volume is lower, generally the CAR T therapy is much better tolerated. Kind of along the same lines, so on the efficacy side, I think academic data from Germany, Dr. Schett's group, feels like it sort of set the high watermark for efficacy with autologous CAR T. I guess given kind of this profile that you're outlining, what is sort of the efficacy profile you'd like to see emerge from 329? Yeah. I mean, so far, I think Dr. Schett updated his data at the ACR covering 35 patients, and the majority of them have, at least during the period of follow-up, which now for some patients extends for more than a couple of years, there is very good control of the disease. I think there has been maybe one case of relapse out of 35 patients. This is, I would say, no matter how you think about benefit-risk, I think this is very positive benefit-risk profile in this patient population, but as I said, right now, CAR T therapy is being tested in patients with severe autoimmune disorders, and when we designed ALLO-329, we were thinking both patients with severe disorders as well as patients with relatively milder autoimmune disorders. Because even in the latter setting, if we can offer them one-time treatment that can provide prolonged remission, I would say that is a success. So eventually, one way to think about it is in the severe cases, what would allow the registration? Is it a single-arm study that can provide a registration? Or do you need a control study? I think those are some of the things that people are beginning to sort of think about. But I would say this is relatively early. Let's just let the data mature. And then I think different companies as well as Allogene, as we generate the data, will develop strategy on how to get the product approved. And as part of that, is Allogene still assessing which indications are the most appropriate? Or do you have a sense of that yet? So the target product profile of ALLO-329 is that this will be available as an off-the-shelf. Okay? So think about it. This is a treatment that will be available on time without the need of complex logistics or leukapheresis, which can be very cumbersome even in hematology setting. And I can tell you that it is very cumbersome in the rheumatology setting. And also, another important target product profile is because of the Dagger technology that comes with the CD70, we believe that we have the opportunity to reduce or eliminate the lymphodepletion. So depending on how you get there, which is part of the clinical study design that we are working on, is that those two target product profiles will broaden the usage of ALLO-329 across different autoimmune indications. And as I said, the way we think about autoimmune indication is, yes, rheumatology is one of the areas of a lot of CAR T studies, but there is also neurology and other indications. So over a period of time, we will continue to look and investigate ALLO-329 across different indications. Fantastic. Let's move to the ALLO-316 program. You mentioned this earlier. This also contains the CD70 targeting Dagger technology. Maybe just walk us through the highlights of those data, and we'll get into it. So we just updated ALLO-316 data at SITC based on 26 patients with metastatic or advanced renal cell carcinoma who have exhausted available therapy. So these are patients post-TKI. So this is tyrosine kinase inhibitors and also immune checkpoint inhibitors, including the patients who are some that have been even treated with HIF-2 alpha. So of those patients that we have studied using different lymphodepletion and different cell dose, we are seeing a relatively good response rate. And if we focus on the phase 1b dose level, so this is the dose that we are expanding the patient numbers, we have seen the best overall response of 50% and confirmed overall response of 33%. And we are following the durability. But of those patients who have confirmed tumor responses, the responses are currently ongoing. So I would say that this is very exciting data for CAR T, not to mention that this is data coming from the allogeneic CAR T in solid tumor. Maybe to add a little context there, so frame for us, what is the unmet need and kind of the profile of efficacy that you want to see in that sort of post-TKI setting? Yeah. So the available treatment after post-TKI, post-immune checkpoint inhibitor, is really another TKI or HIF-2 alpha inhibitors. And also, there are mTOR inhibitors that get used. But I think the usage of mTOR inhibitors has gone down quite a bit. So you're talking about the response in the range of 20% and the duration of response that goes for about 6-12 months, depending on the different treatment. So that's more or less the bar that we sort of see based on the available treatment. And we want to see a response rate that is a little bit higher as well as durability that is comparable. Okay. And then on the safety profile, there were a few sort of grade 5 events. Is this sort of just reflective of the treatment setting, most likely? The safety is something that we follow very carefully. And I would say in the renal cell carcinoma, these are heavily pretreated patients that do not have much options. And also, some of the safety findings occurred when we are pushing the dose as well as the lymphodepletion. So as we gain more experience, we will learn more about the safety profile. But I don't want to underestimate any of the safety findings that we have seen. But given the patient population that we are studying, I'm not overly concerned. We just need a little bit more data. Yep. Okay. Okay. And I think you kind of sort of touched on this. But in your expansion phase, so it's already ongoing. Yes. Is that right? 20 patients thus far? We're targeting about 20 patients. Okay. Targeting about 20 patients. So what do you want to learn from the expansion phase? And I guess, do you have a line of sight yet as to when that data might come? So the main reason that we are expanding the phase 1b cohort, I mean, it's very simple. I mean, we treated so far eight patients, of whom there were six patients who had the right tumor CD70 expression. So additional patients that we are enrolling, as I've said, is to gain more experience on overall efficacy and safety, and especially in those patients who are high CD70 expressors in the tumor. We are currently looking at what the right cutoff of the tumor positivity score. So this is really a measure of what percentage of tumor cells are expressing CD70. So far, the responders that we have seen in the ongoing studies had a tumor positivity score of 50% or greater, which represents the majority of the renal cancer patients. So we definitely want to get more experience in that particular patient population to better establish the tumor cutoff, TPS cutoff, as well as the safety and efficacy data that we have just talked about. That's an H-score, right? So when you say tumor positivity, it's number of cells, but also the density of CD70 per cell. TPS is a little bit different than the H-score. H-score has two components. One is tumor positivity score. The other one is intensity, which they grade from 0 to 3. Maximum tumor positivity score is 100%, every cell expressing the target. H-score, the maximum positive H-score is 300. Got it. Okay. Well, great. I think we're just about out of time. But maybe just the last question, cash runway. We just reported our third quarter. We ended with over $400 million in cash or cash equivalents, which will carry us through into the second half of 2026. In terms of the data flow coming from the different programs that we are talking about here, ALPHA3 study, we expect the initial data readout of the selection of lymphodepletion regimen mid-2025. That will be followed with interim analysis and completion of enrollment in the first half of 2026. Obviously, our cash runway covers through all that. As for the ALLO-329, we expect to file the IND the first quarter of 2025 and have the initial proof of concept data by year-end 2025. Again, it covers. I didn't answer your previous question about the expansion cohort of the ALLO-316. The 20 patients that we are targeting, we expect to update the data mid-2025. I would say the cash runway position is one of our strengths. It carries us into the key readouts across all three programs that we are running. Great. Are there any additional questions in the room? Okay. David, thank you so much. Ben, thanks for having us here. Appreciate it.