Good morning everyone. Tyler Van Buren here, Senior Biotech Analyst at TD Cowen. Thank you very much for joining TD Cowen's, 46th Annual Healthcare Conference. For our next session, we have a presentation, hybrid presentation and fireside chat with Allogene, and it's my pleasure to introduce the David Chang, President and CEO and Co-founder of Allogene, and the Zach Roberts, Executive Vice President, R&D, and Chief Medical Officer. David and Zach, thank you so much for joining me. David, I'll hand it over to you for the presentation. Yeah. Thanks, Tyler, for that introduction. You know, I don't know about putting "the" in front of names, but anyway, I really appreciate inviting us to this exciting conference, except the weather. What we'll be doing is a little bit of a hybrid presentation just to orient everybody about where Allogene is. We've been advancing the Allogene XL therapy for past eight years. When we sort of look at the field, the value proposition of Allogene remains the same, and if anything, has been growing as we understand the clinical utility coming from the Allogene XL therapy. One-time treatment that can provide a durable responses, potentially reaching to the cure, being cured of the disease. Another thing that we have been emphasizing, and this also the noise on this area has gone up, is really improving the patient accessibility. Not only taking away the logistics associated with the autologous cell therapy, but also in our case, as we will talk about, taking the cell therapy to the community-based cancer centers where the patients are cared for. You know, that is a very important advancement that we are making in the clinical programs. Third, where we have more information now than ever before is our growing confidence that the cell therapy as an allogeneic can be delivered at biologic-like scale as well as the cost of goods. We are currently estimating that with a manufacturing facility that we control, we can produce somewhere between 20,000-60,000 patient doses per year at a cost of goods that's somewhere in the $10,000-$20,000. That is a significant improvement in terms of what can be done with the cell therapy. If anything, we feel that allogeneic cell therapy is so close to, you know, crossing the finish line. Another thing that I wanna talk a little bit about, especially in light of different modalities, of T-cell engagers and other modalities that are entering the space. You know, still the allogeneic CAR-T, ex vivo engineered manufacturing brings to unique advantages that comes from being able to do multiplex gene editing. This is something that none of the other competing modalities can do. As I've talked about biologic-like economics and distribution, and also being able to, you know, control the manufacturing, you know, which is really important as we think about the consistency of the product, as we, you know, try to address many different patient population. The, you know, the benefit, you know, that clinical benefit as we talked about, so far nothing has been able to claim a one-time potentially curative approach that comes with the, you know, the cell therapy. With that, currently, the two primary programs that investors are very interested in is the cema-cel CD19 program that we are currently studying in the MRD-directed therapy in the frontline consolidation setting for the large B-cell lymphoma, and the initial data readout is expected to occur in April, is our initial futility analysis, and we'll talk a little bit more about that. The second program is ALLO-329. This is a purpose-built, dual CD19, CD70 program that we are studying patients with rheumatologic disorders. We'll talk a little bit about ALLO-329 as the initial proof of concept data coming from this program is expected to occur in June of 2026. Another program that we are continuing to advance is ALLO-316, CD70 directed program that we have generated the proof of concept response data in the renal cell cancer setting. For the time consideration, we will focus on the first two programs. cema-cel, this is in what we consider as a very unique clinical situation, you know, frontline consolidation. To understand what we are doing with the cema-cel study and ALPHA3 study, I think we have to understand the current standard of care in the frontline large B-cell lymphoma treatment. The main, you know, the treatment options that these patients have is a Rituximab-based chemoimmunotherapy, which is usually given for six cycles. Most of patients' needs are served with the six cycles of R-CHOP based chemoimmunotherapy, but about 30% or more patients, they either progress immediately or they do have a recurrence soon after they complete the R-CHOP treatment. However, there is really no way to understand who's gonna have a disease recurrence versus who's gonna continue to enjoy the cure. There was no way to tell that until, you know, recent progress that has been made in the, you know, circulating tumor DNA approach MRD assay that gives a lot of visibility into being able to predict who may have a disease recurrence. That's really the essence of what we are trying to do in the frontline, you know, consolidation study. We do not try to change this well-established R-CHOP-based chemoimmunotherapy. We let the patients and the physicians complete the, you know, the six cycles of R-CHOP chemoimmunotherapy. At the end of the treatment, we test them for the presence of MRD. If they are MRD positive, they are eligible for ALPHA3 study. Here, this is really, you know, the purpose of reducing the risk of recurrence. Hopefully, that will lead to the elimination for the need for the second line or subsequent line of therapy, which we believe is a great value to the patients and the caregivers. Conceptually, this is a seventh cycle, you know, that's given after the R-CHOP, and after that treatment is essentially done. We believe that this is providing the right product, a curative treatment that comes with a CAR T to the right patients who needs the treatment, not necessarily patients whose need will be sufficiently addressed by the R-CHOP treatment at the right time when the disease volume is at the lowest. We're talking about people who have a molecular level of disease, which has shown repeatedly that patients with low tumor volume, they are the ones who benefit mostly from CAR T. We believe that this is the ideal, you know, time to treat the patient. Also, as I've talked about before, treating patients in the community-based cancer centers at the right place, where 80% or greater, you know, percentage of patients with a large B-cell lymphoma are cared for. Going back a little bit about why do we believe that MRD-guided therapy will be so effective in this setting is illustrated on this slide. If you look at the on the left side, Kaplan-Meier curve, two curves that are shown, patients who have done MRD testing and at the end of the six cycles of R-CHOP, and they are separated by whether they're MRD negative, which is shown on the blue line. These patients essentially do not have a disease recurrence. These are not the patients that we are interested in the ALPHA3 study. On the other hand, if you look at the red line, these are MRD positive patients. These patients would have a disease recurrence, within first two years, up to about 80% of the patients. If you look at the median time to disease recurrence, we estimate that to be about four to six month after completing the R-CHOP treatment. This is really the power of MRD-guided treatment that we are integrating into the ALPHA3 study. The second point that we have made earlier is catching the patients at the MRD-only state, you know, basically allows you to catch the patients at, you know, several-fold, 200-fold lower disease volume. As I said, this is really molecular level of disease evidence, and we believe this will lead to much better benefit coming from the curative treatment of the allogeneic cell therapy. This is illustrating the study design. Patients who are MRD positive, they are randomized one- one to either cema-cel or the observation, which is considered to be the standard care. There are 3 key, sort of, data communication that we had planned on. The first one of which we expect to occur in April of this year is interim futility analysis. You know, following that goes to office pending analysis, interim EFS analysis, and the primary EFS analysis. Trial design, we talked about it being a randomized, and it's designed with the FDA guidance and concurrence about the design as well as endpoint. We are planning to enroll approximately 220 patients who are MRD positive at the end of the frontline treatment. Primary endpoint for the study is event-free survival, and the key secondary endpoints are PFS, overall survival, and MRD clearance. What we intend to communicate at the interim futility analysis is the MRD clearance rate, in 24 patients will be subject to the interim futility analysis. The bar that we have set for the interim futility analysis is that with a cema-cel treatment, there'll be absolute improvement in the range of 25%-30% in the MRD clearance. How we set this bar is really, illustrated here. The first one is, what is the regulatory benchmark? That's really coming from the POLIVY that was approved in the frontline large B-cell lymphoma about three years ago. 27% reduction in PFS risk and improving the 2-year progression-free survival rate by moderate 6.3%. The second key reference point is what the autologous CAR T has done in the second-line setting. There, about 30% improvement in the objective response rate compared to the autologous stem cell transplantation led to a threefold increase in median Progression-Free Survival and Overall Survival risk reduction of 27%. What we reference is somewhat relevant in terms of study design, that was done in a different tumor type, muscle-invasive bladder cancer, where patients after undergoing a bladder resection, if they were MRD positive, they were randomized to treatment or the observation. Here, a small minimal MRD clearance differential of 11% led to a significant reduction in death as well as risk of recurrence. That's why we believe being able to demonstrate 25%-30% improvement, absolute improvement in the MRD clearance will be very meaningful at the interim futility analysis. Now let me move to our second program, ALLO-329. This is a program that we are currently studying in autoimmune indications, specifically rheumatology indications of SLE, myositis, and scleroderma. This is really built for the purpose of advancing the allogeneic CAR-T into the autoimmune indications. It's made with a very simple manufacturing process, introducing dual CD19 and CD70 CAR constructs into the TRAC locus using site-specific integration, which leads to a very high yield as well as a very consistent product without having to use the lentiviruses. What's behind this is what's coming from the CD70 part of the CD19, CD70. This is the essence of the Dagger technology. What being able to target CD70 allows you to overcome allogeneic rejection issues that's a challenge for the allogeneic CAR-T therapy. Also it allows the, you know, the ALLO-329 to expand preferentially as it encounters CD70 positive T-cells in the patients. Currently the study is ongoing as a dose escalation study. We intentionally started at very low cell dose of 20 million cells and plan to go up through the dose escalation using either very minimum lymphodepletion of Cytoxan alone or no lymphodepletion whatsoever. This is really with the idea when we think about the patients with autoimmune indications, having to use the lymphodepletion is as a barrier. We want to minimize or eliminate the lymphodepletion as much as we can. We have sort of indicated that the initial proof of concept data coming from 329 will be in June of this year, and that will cover at minimum the 1st dose level patients treated in this three plus three design. We will cover, you know, disease-related biomarkers, cell kinetics, as well as CAR-T expansion and any clinical data that's available, you know, with a minimum follow-up at the time. Let me conclude the sort of presentation by really where we stand. I think we are moving, you know, across many different indications that will be served very well by the allogeneic cell therapy MRD positive setting. I think this is a concept that can be extended to other disease setting, both the hematologic cancers as well as in other solid tumors, and also in autoimmune indications outside oncology, where a transient depletion of the B cells or T cell could serve to reset the immune system. With that, we will move to the Q&A. Great. Thank you very much for the presentation, David. It was very helpful, defining kind of that 25%-30% MRD kinda conversion rate delta as the bar. Can you just elaborate on again, why you decided to take this futility analysis, the significance of it, especially as we think about how it might translate to, you know, the later readouts in EFS? In terms of how it's gonna translate to the later readout of EFS is really coming from the second line study of autologous CAR-T. Let's just make one very simple assumption, MRD clearance and, you know, if you equate the MRD clearance to the achieving complete remission, okay? In the second line setting, about 30% differential in the complete response rate translated to the hazard ratio that was in the 0.4-0.5 range for the EFS and PFS, you know, with the autologous CAR-T study. I think there is a very good reference point that will indicate 30%, 25%-30% improvement in the MRD clearance will translate to a meaningful difference in the clinical outcome that we're using for the ALPHA3 study. What do you expect, in the watch and wait arm? Is it possible that we could get spontaneous conversion from MRD positive to negative in the control arm? It's absolutely positive, Tyler. In fact, we expect to see one or two patients potentially spontaneously converting and that is also sort of foreshadowed by the data that we have from the Foresight test, some of which David just covered with the Kaplan-Meier curves illustrating that about 20% or so of the patients who are MRD positive at the end of frontline treatment never progress. We expect those patients potentially to be the ones that spontaneously convert. We've modeled that in the overall statistical design of the study. For specifically this upcoming futility analysis, we do expect to see potentially one or two patients going from MRD positive to MRD negative, which is why we are emphasizing the delta as what's important because some patients in the treatment arm will also spontaneously convert, so we'll get credit for those on both sides. Understood. With the interim futility coming early Q2, I guess potentially next month, is there anything else in terms of data or guidance for the rest of the trial that you plan on disclosing during that readout? Yeah. The MRD clearance is a very important point 'cause in our view, the clearance in the MRD, you know, that we have guided, that's gonna significantly de-risk, you know, eventual outcome as we look at the event-free survival, you know, in 2027. Another thing I, you know, we've been asked a lot is, you know, and I think this is somewhat relevant, and we will include that in the, in the data communication, is the preliminary safety findings coming from the patients that are treated. Keep in mind that some of these patients have been treated in the community-based cancer centers with the no CAR T experience. I think one of the essential things that we have to demonstrate is that cema-cel in the frontline consolidation setting can be safely administered as an outpatient, and patient can be managed totally as an outpatient. I think that will be a very important information. We intend to provide some color to the safety information coming from the ALPHA3 study. If the, in MRD conversion data is blowout, like way above expectations, is it possible you could go to the FDA and talk about filing, or do you need to wait for the interim EFS? How much data do you need to file cema-cel, in this setting? Yeah, we get asked that question a lot, but, you know, let's do step by step. I mean, this is the first, you know, futility analysis and, you know, it involves about 24 patients. Now, you know, if we were to reuse this study as a registration intent, I don't think 24 patient will be sufficient. Certainly it will give us a lot of indications about what the future may unfold as we continue the enrollment. You know, which by the way, I mean, there is a lot of excitement on this study, and the currently studies are ongoing in North America with close to 60 sites activated. As we sort of think about, you know, eventual event-free survival, I think we make a little better sense based on what we see in the MRD clearance. Understood. Since you mentioned excitement and sites, can you talk about where you are in terms of activating sites? Are you still activating more sites, and how is enrollment progressing, and where are you in terms of enrollment completion? We have guided towards completing enrollment by the end of next year, so we'll talk a little bit more about those plans when we do the interim futility data announcement. In terms of our footprint in the trial, we are constantly adding more sites. At the last update, I think we had 59 sites open. We're above that number now in North America. We've also talked about opening Asia Pacific sites, Korea and Australia. That progress is being made there as well. We regularly field unsolicited inbound interest in opening the study from sites around the globe. As people learn about this trial, they see the potential to administer CAR T to these patients in these settings, and they get excited. We're fielding those requests all the time. Also from some of the sites that, you know, when we initially approached, they, you know, for one reason or another, wasn't able to do that. Now they're raising their hand and says, "Can we have the study back? On the testing front, maybe you could just remind us again how long it takes. Obviously, this wasn't feasible previously, till your collaboration and your development. How long does it take to get the results back, and how easy will it be to scale that testing upon commercialization? The results come back pretty quick. Under two weeks regularly, sometimes even 1.5 weeks in the context of ALPHA3. We expect that to be the turnaround time in a commercial setting as well, roughly. There's not a four week lead time, which is sometimes there is the case for some of these more advanced diagnostics. That does not apply to the Foresight test. You know, we envision this to be part of the standard of care in terms of it, you know, when you complete your frontline treatment, what is your prognosis? It's not just PET CT anymore. It's gonna be MRD test as well, and you need to have a test that comes back quickly to inform those conversations for the patients. Okay. I would also say, you know, within, you know, last, you know, 18 months while we've been doing this study, the idea of MRD testing has undergone, you know, pretty significant changes. I mean, more and more sites, even outside our clinical trials, are beginning to use commercially available MRD assay. Just like in oncology, in a solid tumor, you know, the MRD-guided treatment, I think, is going to be the next big frontier. As it happens, you know, the study that we're doing with ALPHA3 is one of the, you know, the key studies in that area. The doctor gets those test results back, goes to the patient and says, "Unfortunately, post R-CHOP, you're MRD positive. You still have cancer cells floating around your body. Would you like to try cema-cel or wait for it to progress and come back in second-line treatment? Precisely. I think that most patients, that's a pretty obvious choice, to sort of take control of your treatment, you know, address this residual disease, hopefully, you know, achieve a cure, as opposed to rolling the dice. You know, clinical relapse can take many different forms, and some of them are catastrophic. It's pretty, it's pretty commonsensical that a patient would opt to do a therapy that is outpatient-friendly, one-time dose. As long as safety is good. What's your level of conviction in the safety? Well, I mean, as as we've said, not only are we starting with a product that is generally better tolerated than I think some of the autologous products, and we've demonstrated that in the phase I relapse refractory setting with 0 cases of high-grade CRS and ICANS, as David illustrated in his opening remarks, efficacy improves with low disease burden, but so does safety. This has been shown now repeatedly in multiple different contexts. We are running this study in a clinical context where it is the lowest measurable disease that you can treat a patient with. It's reasonable to expect that the safety profile that we saw in the relapsed refractory setting would be improved from there. Again, coming back to this idea of the right patient at the right time and in the right setting. That's great. Wanna get to autoimmune here shortly, but just to wrap up cema-cel in the frontline, could you just like elaborate on the market opportunity? How large you think this market could be, especially as we think about the current CD19 second-line plus market? Yeah. When we have done some, you know, high-level analysis and we continue to refine it, I mean, you know, we currently project that, you know, combined patient number, you know, that would fall into the category of MRD positive or insufficiently treated after R-CHOP. When we add up those numbers, the number goes up to about 34,000, you know, US and Europe. You know, that leads to the TAM of about $5 billion. Obviously, as we advance the program, you know, we have to, you know, layer in what we are actually seeing in the clinical efficacy and the market penetration. You know, you're probably talking about, you know, product that could reach a peak sale well over $2 billion. Great. let's move to ALLO-329 in autoimmune. You mentioned, the differentiated approach, the phase I trial's ongoing, proof of concept data by the end of the first half. Can you elaborate on what you expect to report from that phase I study and what the ultimate goal of that phase I study is? Yeah. David mentioned that we started our dose escalation at a low dose, 20 million cells. It is a standard three plus three dose escalation, we're, you know, with DLT windows and so forth, we're having to follow these patients, you know, one at a time. It'll be the first handful of patients that are treated. The study schema showed that we're doing these two dose escalations in parallel, we're having patients treated with Cy and with no lymphodepletion. We do expect to be able to share data from both dose escalation pathways. As far as the specific data that we expect to share, all focus from internally is gonna be on biomarkers and whether this, whether we're able to validate the Dagger biology in this product, which is a key part of its design. Looking for persistence of the cells expansion with light or no lymphodepletion is gonna be tremendously validating. Of course, we'll have clinical data as well, we'll share any kind of disease score improvements or markers of disease activity like autoantibodies or so forth. We'll share that data too. As far as I'm concerned, I'm really looking mostly at the cell kinetics and whether the Dagger is able to keep these cells around for a period of time in these patients. Okay. It'll be a few months of follow-up that we could expect from these patients? Correct. Okay. All right. Regarding the biomarkers, are there any specific data points that will tell the kinda CD70 targeting arm story of 329 that we should focus on or? Yeah. In the RCC program where this was first validated, we saw clear evidence that the host T-cells that were CD70 positive were depleted more significantly and for a longer period than the host CD70 negative cells. Over the course of the RESOLUTION trial with ALLO-329, we'll be looking for very similar markers of Dagger activity. Okay. Is it fair to say with the Dagger technology, which I continue to think is awesome, you know, using kinda the weakness of the rejection as a strength, right? Is it fair to say that you are confident that it will reduce lymphodepletion? Or can we get as confident it's going to potentially removing it? Or is reducing versus removing lymphodepletion something that needs to be explored in the early phase of the clinical program? The short answer is it needs to be explored. We designed the study to test this hypothesis right up front. We have evidence that the potency of the Dagger effect grows with more rejection activity, so it bears out that a patient with less lymphodepletion is gonna have more allogeneic rejection activity. It is possible that we see better cell performance in the absence of lymphodepletion, but we have to run the study to see that. I mean, you know, I would go one step further. I mean, we felt confident enough when we designed the study, you know, we are not using Flu/Cy, which is a standard lymphodepletion. You know, we already took out Fludarabine and only using Cy as the beginning point. A lot more confidence that Cytoxan alone may be sufficient for lymphodepletion. No lymphodepletion is a little bit of a, you know, stretch that we really have to see the data. You know, frankly, just going from Flu/Cy to Cy alone, that is a tremendous improvement in reducing the burden of the lymphodepletion, as well as potential toxicity that may be coming from, you know, using two regimen, chemotherapy regimen versus just one. Yep. Certainly haven't seen that in oncology, so big step. Mm-hmm. Okay. If these data are positive and as good as you hope they are, what are the steps forward for the program, and what indications are you most interested in for a pivotal program? Well, in terms of pivotal, we haven't really talked about it. The way that we think about autoimmune space is that, you know, there are a number of different, very meaningful indications where unmet medical need is high that we can really think about. You know, rheumatology is the first, you know, therapeutic area that we are covering with the RESOLUTION study that we are doing with ALLO-329. Same can be said about what can be done in potential nephrology indication, IgA nephropathy, neurology, myasthenia gravis as well, multiple sclerosis, where there is some growing evidence that the CAR T is working those indications. You can even, you know, take that to one step further, where the data isn't that, you know, much out there, bu type 1 diabetes is a ver t y, you know, autoimmune dependent destruction of the T cell dependent destruction of the islet cells. There are also inflammatory bowel disease, you know, that has a lot of autoimmune components. I think, you know, we will have to do some digging and prioritize the indications, you know, after the proof of concept. You know, the opportunities with this program is just enormous. Yep. All right. That's helpful. We're over time, but maybe just to close out, David and Zach, I'll ask you both, what you believe is the most underappreciated aspect of the Allogene story by investors right now. I think that the ALPHA3 study, I think it gets due attention, but I think that there is still the transformative potential of this trial, I think is not broadly appreciated. If it's a positive study, it really has the opportunity to upend care of frontline lymphoma patients in a way that we haven't seen in a quarter of a century. I think that that is a little underappreciated. Yeah, I mean, you know, I would also say that, you know, past few years, I mean, after initial influx of many different players in the Allogene cell therapy space that was followed by, you know, lukewarm or negative, you know, result from the studies that they have done. There's a lack of interest in the Allogene. As we stand now, as we look at the programs, I mean, you know, I feel that Allogene is so close to finishing the cross line. I think that is probably the biggest picture that a lot of investors are missing. Wonderful. David, Zach, thank you very much for your discussion. As always, love to have this kind of inner conversation with you, Tyler. Thank you very much for inviting us. Thanks, Tyler. Thank you. Thanks, everyone.