All right. Good morning, everyone. Welcome to Jefferies 2026 Global Healthcare Conference. My name is Roger Song, Senior Analyst covers mid-cap biotech. It is my pleasure to have a fireside chat with our next company, Allogene Therapeutics. We have CEO, David Chang, and then CMO, Zach Roberts. Welcome, gentlemen. Thanks. Awesome. All right. Thanks for having us here. I would sort of correct, Zach Roberts, he's the CMO right now. Yes He's the new incoming CEO. I want you to make that introduction. Yes. Awesome. David, why not you give us a state of our two minutes about Allogene, and then we definitely have a lot to talk today. Yeah. Two minutes, the way that I talk is relatively short time. I'll try to be as succinct as possible. I'd just like to point out one thing that as I'm sitting here as soon to be outgoing CEO, Allogene was launched in 2018, and it was launched at the Jefferies Global Healthcare Conference. Different analyst, still Jefferies. I think that also brings out a point that in a course of organization, I always view that in a transition, can be very positive. I've been at Allogene for eight years, sort of growing what was a nascent concept of allogeneic cell therapy. Going through some growing pains and understanding the science. When I think about 2026, where we stand, the strategy that we set out about three years ago, instead of pursuing relapse refractory setting, putting the allogeneic CAR T, not just trying to differentiate that from the science perspective, but from the clinical perspective, moving into the earlier line. Now that we have seen the interim futility analysis of MRD clearance rate differential that we have released earlier, I would say that strategy is panning out, and ALPHA3 study, at this point, looks extremely good. Not only that, we also have launched our autoimmune program, and we have provided a little update in our latest earnings call, where we have indicated that we're beginning to see clinical responses in the ALLO-329 program. Pipeline moving along very well. Also, we have recently financed, taking away any kind of financial overhang, giving us a runway to 2029. The company is in really good place. With that, I feel that the right time is now to make the transition. Zach was brought in specifically not only to lead the clinical programs, but eventually as my successor. I've known Zach ever since he entered industry, and we have worked very closely. I think this transition is very timely, and I think it's going to be very good for Allogene. Also, I'd like to point out, I'm not stepping away. I will continue to be on the board, and will be very involved with the company going forward. Excellent. David, you absolutely will be missed, but you're not away. You're still with Allogene, Obviously you are in good hands with Zach. Maybe Zach, do you want to take a minute to-- What's your history with Allogene, with David, and then with the company? Yeah. David's absolutely correct. He actually helped recruit me out of academia to Amgen, and then I followed him to Kite. I've been working directly with David, Arie, and Christine Cassiano, who leads our IR team, for 11 years now. I joined Allogene in 2023 and have had a really excellent time running the R&D team, and I'm very excited to take over for CEO. Awesome. All right. The biotech company, obviously the top leadership is paramount, and then also you have a very impressive platform. Recently, I think David just mentioned that you reported some very important data from cema-cel, and then some of the other early pipelines. Why not we take a couple of minutes to talk about the cema-cel as the focus. What we have seen for the interim readout for the MRD negative for the LBCL, and then how this will translate into the EFS later next year. Yeah. We know a growing amount about MRD and its relationship to EFS. This has been shown now in lymphoma as well as across multiple other solid tumors and other clinical settings. The results that we showed in April from the interim futility analysis, which indicated that cema-cel, when delivered as a consolidation treatment for patients who remain MRD positive after first-line treatment for large B-cell lymphoma, we were able to clear 58.3% of those patients' MRD, moving them from MRD positive to MRD negative. Based on historical data from lymphoma using the very same test that we're using in ALPHA3, a test called PhasED-Seq, we do expect that this is likely to translate into a strong EFS. For example, in the TRANSFORM study of Breyanzi in the second line, they illustrated a 24% improvement in MRD clearance between the CAR T arm versus the standard of care arm. That translated into a 63% improvement in the risk of EFS in the final analysis, also translating to a very significant, about 27% delta in the plateau of those two curves. Highly prognostic for these patients. As David mentioned, we think that ALPHA3 is in a very good place right now, and it's really on the strength of that interim data that we believe that we are headed towards a good outcome for this trial. Yeah. When we assumed the coverage about Allogene a couple of months ago, we went through all the literature, tried to link the MRD negativity or the delta, the achievement to the EFS. We do see the evidence, we have to say, you are still the first one to demonstrate in this setting with this modality. Inherently you have some risk uncertainty there, I think we have enough to say you have a good chance to be able to achieve that. Did that resonate with you in terms of the risk and some of the evidence? Yeah, absolutely. I think that the ALPHA3 study is really the culmination of quite a number of years of us learning how best to use CAR T cells in patients with cancer. We have known for quite a number of years, based on a growing body of evidence, that treating patients with low disease burden, even with autologous products, tends to lead to better outcomes, both on the safety side as well as on the efficacy side. As the MRD data itself was beginning to mature, and we could see that MRD status at the end of treatment really did carry a very strong prognostic sign, and that if you're MRD positive, you're likely to progress. If you're MRD negative, you're likely to be cured. That gave us an opportunity to treat patients at the lowest possible disease burden, and that's exactly what we're doing in ALPHA3. While you're correct that this is the first time someone is using CAR T cells as a consolidation, it really is a natural outgrowth of some of the observations that we've been making as a field for the last several years. Roger, it'll be a miss if I did not point out, this is really brainchild of what Zach has done. The uniqueness, the innovation that the ALPHA3 brings. Frontline treatment of large B-cell lymphoma, that is a very well-established treatment. About 60% of the patients do well with a standard treatment. What we are doing is trying to address those 40% whose needs are not insufficiently met with existing treatment. Rather than just adding to the existing treatment, which obviously could potentially create toxicity, but it's really over-treating 60% of the patients who do not need a treatment because they do well anyway. That's where the MRD is coming in to identify those patients who are likely to relapse. The ultimate goal is to improve the cure rate of the frontline treatment with one additional cycle of consolidation. This is a very innovative concept. Frankly, the concept of consolidation really came from the treatment of leukemia and lymphoma in the early days. From the high-level thinking, this is why the study resonates so well with the key opinion leaders as well as the study investigators. Another thing that we felt was very important is that we know the transformative potential of the CAR T, the curative potential. One of the limitations of CAR T being widely used is its manufacturing and also the logistics that comes with the manufacturing and administration, which limited the use of CAR T to specialized CAR T centers. ALPHA3 study is really trying to break that barrier by taking the study into the community-based cancer centers where patients are being treated and really taking the treatments to patients' zip code and thereby making the treatment more widely available. Zach mentioned, in the futility analysis, another thing that was extremely interesting, and we believe it is very important, is the safety profile that we have seen. Most patients were treated as an outpatient and was managed as an outpatient. It really gives us good initial proof of concept that this treatment can go to the community-based cancer centers where the patients are cared for. Yep. That's right. By the way, investors, sometimes they ask me or maybe they have some question related to we haven't have any consolidation for LBCL, which may be true because it's not in the standard of care, but I think Zach you know some of the years ago, they do have some transplant for the consolidation therapy. The outcome is kind of a mix. Can you give us some background? How should we think about that translation to this cell therapy compared to the past consolidation for LBCL? For any consolidation strategy to be useful, consolidation is the term that we use for adjuvant therapy in heme malignancy, and we've used it in acute leukemias. In myeloma, we use transplant in myeloma. In solid tumors, we use adjuvant therapy all the time. Those are the same two concepts. For adjuvant or consolidation treatment to be useful, you need two things. You need, number one, an accurate way to identify high-risk patients, and number two, you need an efficacious treatment. In those historical experiences in LBCL, they tried to use bone marrow transplant. However, they did not have a very good way of selecting the patients who would benefit the most from that consolidation therapy. While there was a trend towards improvement in adding bone marrow transplant to patients with LBCL who've completed frontline and are in remission. It was not statistically significant. However, in a post hoc analysis, they went back and looked at the very highest risk patients, and there they did see a signal there that was beneficial. That is additional evidence that this strategy of selecting high-risk patients and then using an efficacious therapy could be beneficial. In ALPHA3, we've improved both of those variables. First, we're using MRD at the end of treatment. Effectively, we are finding residual tumor in these patients. It's not a matter of risk, it's really a matter of was this patient cured or were they not? Secondly, we're switching away from a chemotherapy-based treatment, which is what auto transplant is, into CAR T-cells, which of course we all know are highly efficacious for Large B-cell lymphoma. In ALPHA3, we've optimized both of the two variables that you need for a successful consolidation or adjuvant strategy. Okay, good. All right. The other thing is people keep asking, and I believe you have a reason to do that, is you take a snapshot of the MRD negativity a couple of weeks ago. How much the kinetics we know, and how do we expect the kinetics going to change over time? Will that be even more favorable as they keep this down, or the delta will continue to be wider? Just to remind everybody, the ALPHA3 is a randomized study, and the patients are either allocated to the standard of care, which is observation, so no further treatment. We just watch these patients in the usual way versus a dose of cema-cel following Flu/Cy. In the data that we released last month or in April, we looked at the kinetics of MRD clearance in addition to the overall status of the clearance. The data that I cited a moment ago was the MRD status at the last assessment that the patients had undergone. We also paired that with just a snapshot at the first measurement of MRD after randomization, the day 45 MRD assessment. At that day 45 time point, we saw a median decrease in the cema-cel arm of 97% of the circulating tumor DNA. In contrast, in the patients in the observation arm, we saw a median increase of about 27%, sometimes referred to as molecular disease progression. We expect when you give a single infusion of CAR T-cells that most of the tumor killing is going to occur very quickly after that infusion, and beginning probably within the first few hours and maybe lasting for the first week or two. Even in the relapse refractory setting, most patients who achieve remission do so by day 28. It was very reassuring to see in this analysis that in fact, most of that tumor clearance was occurring by the first time that we measured MRD. We expect, as that first time point illustrated in the observation arm, that the patients who do not receive any further care will continue to have molecular and eventually clinical disease progression. That is the natural history of patients who are MRD positive after their first-line treatment. We do expect those curves will continue to separate with time. Yeah. They don't get anything and then just observation. Correct Maybe early on, I would say some risk they will may get to MRD, but majority of them will lose MRD if they are not getting treatment over a long time. That's the delta will kind of get wider. Correct. Yeah. With no further treatment, we expect that MRD to become clinical progression. Yeah. In terms of the EFS, we know the current guidance is you're going to take internal look mid-next year. What is the statistical assumption there? I don't know if you disclose or high-level disclosure about that, and then what will be considered as clinically meaningful EFS delta at the interim look? We've recently disclosed that the overall target hazard ratio for the study, not at the interim analysis next year, but at the primary analysis, which is currently scheduled for mid-2028. We've designed the study statistically to illustrate a 50% reduction in the risk of EFS events, so a hazard ratio of 0.5. Specifically for the interim EFS analysis that we have planned for middle of next year, it will be conducted on a smaller number of EFS events, so that does change a little bit the powering of that analysis. We haven't gone into the details of what that could be. Only to say that based on the MRD results that we showed at the futility analysis, that we think that that is an interim analysis on EFS that could be positive. Of course, we wrote it knowing that we had a chance of it being positive, but we're pretty encouraged based on the results that we saw in April. Yeah. I have to say, I have a couple of investors reach out to me and say, based on this MRD negativity data, interim going to hit, but we'll see. I don't want to set the expectation too high, but that's the chance to show the benefit at the first interim next year and then the final result, 50% hazard ratio. That's clinically meaningful, I think. Absolutely just come back from ASCO. I think 50% risk reduction in the setting is. Absolutely. As David very rightly pointed out a moment ago, the safety profile here is really, you have to take that into account, right? These patients are in remission. They're doing well. They're probably as healthy as they've been since they were diagnosed with lymphoma. Having a product that is very well-tolerated, can be administered as an outpatient. The patients generally did not need to be readmitted to the hospital. In fact, there were no treatment-related hospitalizations in that interim futility analysis. No tocilizumab, no steroids were given either before or after the cema-cel. That safety profile means that hitting a hazard ratio of 0.5 or better is absolutely highly clinically relevant because it's letting these patients get into that cured category with really very little risk of toxicity. Got it. Okay. Fast-forward, let's say EFS hits either at interim or final, you can potentially file for approval. How big the market it is? Just walk us through the TAM and the haircut there, and then maybe ask another question, a follow-up question after. There's quite a number of patients who are treated for first-line Large B-cell lymphoma, somewhere in the neighborhood of about 30,000 diagnosed in the United States each year. Most of those patients will undergo curative intent first-line therapy. We estimate that the TAM here is about $5 billion between the U.S. and the EU5. One of the questions that we often get is how prevalent is the MRD testing today and how prevalent do we expect it to get? It's probably around one in five, one in four patients undergoing MRD testing routinely at the end of frontline treatment. Primarily, that's driven by doctors' and patients' desire to understand their prognosis better than what can be offered by the current PET-CT disease assessment approach. We know from lots of historical data that MRD status, especially MRD negativity, does significantly improve the quality of that prognosis. Most of those tests are being ordered for that now. Currently, there is no approved therapy that can be administered based on the MRD test result alone, and that is in fact what ALPHA3 is designed to do. ALPHA3, if positive, cema-cel will be the first drug that could be used in response to an MRD positive result. We do expect, and we're seeing now quarter-over-quarter growth in MRD utilization as it stands today. We have done some fairly extensive market research already, talking to KOLs as well as community oncologists, about 30 in a blinded survey using blinded product profiles. In that survey, we noticed that the expectation around MRD utilization will actually jump to probably 75% or 80% once there is an opportunity to actually respond to the MRD positive result. One of the things that's holding docs back now is what do you do with a positive result? In the context of an approved agent, that question goes away. Even with the haircut around MRD utilization, we will have a sort of competition-free opportunity here. We expect that the market opportunity for cema-cel could be about $2.5 billion-$3.5 billion between the EU5 and the U.S. at the time of launch. How about the MRD testing as a positive in that population? What's the assumption there? One of the questions we're getting is the first-line LBCL may evolve over time. We know that autologous CAR T is doing this, and then maybe T-cell engager, maybe some others, they're doing this. How this MRD positivity will change? Maybe the quick one is just want to highlight is your ALPHA3, if it's positive, the potential label will be pretty unique. After any first-line treatment and then the other line, they are positive on the MRD, you can use cema-cel. Is that true for the? That's how the study is written currently. Any standard regimen, right now that's R-CHOP and its variants or polatuzumab R-CHP. Those are the two regimens that are currently approved for use in first-line LBCL. We obviously haven't had any label negotiations yet. We're still running the study, so we don't know exactly how that's going to look. I think most likely it would be after any standard frontline regimen, if you remain MRD positive, then you would be eligible for cema-cel, should cema-cel be approved in this context. First, the question around what is our sort of market opportunity or share of market in that first-line consolidation setting? We expect, based on that same market research that I just mentioned a moment ago, that about 50%-70% of practitioners would use cema-cel to respond to an MRD positive result. We feel pretty good, and that's probably a fairly conservative estimate. That's how we get into that $2.5 billion-$3.5 billion market opportunity. As it pertained to the second question that you asked around what does the evolving first-line landscape mean for that market opportunity? There was some data at ASCO just this past weekend, both some pivotal data with the CD19 monoclonal, the tafasitamab regimen plus R-CHOP, as well as some new data cuts with the bispecifics and the glofitamab. In all three cases, these are all proposed to be first-line regimens. There's ongoing phase IIIs with TCEs as well as the glofitamab plus R-CHOP. In all three cases, clearly there seems to be an improvement on the efficacy to R-CHOP. It's, I think, up for discussion whether R-CHOP is the best comparator in that context, given that pola-R-CHP is becoming more and more prevalently used in this context. Secondarily, there's I think some safety concerns with those regimens and whether a significant fraction of doctors and patients would opt for a more intense and more toxic regimen at diagnosis, given the fact that R-CHOP or pola-R-CHP is actually really good at curing patients with lymphoma, even in the highest risk subsets. Close to 50% of these patients are going to be cured with that regimen, which can be delivered safely as an outpatient. The requirement for inpatient dosing, CRS rates of 25%-40% in some cases, high rates of febrile neutropenia and infections, these are all I think would be concerns for doctors and patients. Knowing that you could treat with an R-CHOP or a pola-R-CHP, get to the end. Ask the question, did this regimen cure me of my lymphoma using the MRD test? If it didn't, to then have the option for cema-cel, I think would be a very attractive option, even in the context of those frontline approvals. Yep. Got it. Just to reiterate my points, R-CHOP takes care of about 60% of patients. The beauty of ALPHA3 study is that there is no over-treatment. Essentially, the patients who are destined to do well, we do not touch them. We identify those who have a residual disease with the MRD test, and they are the target of our population. I think in terms of healthcare utilization, this is probably one of the most effective way to not only develop the drug, but in the future utilization, taking into consideration about not over-treating and only treating the right group of patients who need the treatment. Yep. Got it. Maybe just a follow-up on this. Right now, R-CHOP, about 60%, they are cured MRD negative, and then 40% is positive. How should we think about those potential new first-line treatment? Would that MRD negativity will change? I think on the other side is, I think that you mentioned, David, you mentioned as well, those are toxic drugs, that they may not over-treat. Maybe they won't use that. Weighted MRD positivity may be much lower than if everyone used first-line TCE. Yeah, I think we have to wait for the pivotal results. We have the tafasitamab lenalidomide data from this weekend, and that was published as well. We can look at that carefully. I would say that was a modest improvement over R-CHOP on the PFS side, similar to what polatuzumab in the POLARIX trial showed, about a 6% or 7% improvement to PFS at two years. I think advances are important for patients, and having more frontline options is a good thing. I don't see this or even the TCEs significantly reducing that market opportunity in the number of patients who are MRD positive at the end of treatment. It's just between the toxicity of those regimens, their complexity, as well as the reliability of R-CHOP, the likelihood of there being a significant reduction in the rate of MRD positivity in patients with LBCL is pretty low. Excellent. Okay. We did spend decent amount of time on the cema-cel, which is your lead program. David, you mentioned earlier, just recent earnings, you released some early look of the autoimmune ALLO-329. How should we think about the next step from here? It seems you want to move forward with additional dose in the patient, how the strategy over there in terms of indication selection and also the expansion into the late-stage development. Yeah. The program that you're talking about is our ALLO-329. It is highly differentiated product. It's a dual targeting. The target for the ALLO-329 is CD19 and CD70, with the idea that not only we sort of tackle the B cell dysfunctions that contributes to autoimmune disorders, but also targeting CD70 positive cells that underlie pathogenesis of the autoimmunity. That's a very differentiated program. We sort of intended for the product to be used with the low lymphodepletion or possibly even with no lymphodepletion. We've been conducting the study for past six months, since we first enrolled the patient back in November. I have to say the investigator enthusiasm for that study is extremely high. We were able to enroll nine patients, essentially completing first two dose levels within a matter of four to five months. The study is enrolling, and we are very excited. We are not quite ready to fully analyze and detail the data, but early signs are that patients are responding clinically, to the point that we are constantly getting calls from our investigators about, "We are seeing something that we are not expected to see in this patient population." We are very excited about it. Study is enrolling extremely well, and the next update, which we are planning towards the fourth quarter, is really going to not only carry the longer-term follow-up on patients who have already been treated, but patients who are also being treated now at the higher cell dose level. We so far have tested 20 and 40 million, and we're testing 80 million cells, which is in the range that we may start seeing some meaningful effects. We are very excited about the program. Stay tuned. Awesome. Yeah. This is certainly, it's a huge optionality, and then not in the current valuation for Allogene at this moment. Maybe just last 30 seconds, what's the cash runway, and then what is the most important catalyst for the rest of the 2026? With our recent financing, our cash runway goes into the first quarter of 2029. That covers not only the interim analysis that we have talked about in the cema-cel ALPHA3 study, but also study completion in the primary analysis and possibly even BLA submission. I would say that our cash position is really strong, and what's really left is stay on course, execute ALPHA3 study, deliver the data, and probably the biggest unknown is what we will see in ALLO-329 study. If autoimmune program gives a strong indication, that's going to be another tremendous opportunity where we can advance the allogeneic CAR T for the patient care. Excellent. All right. Thank you everyone for listening and watching, and thank you, gentlemen, for joining us for the conference. Thanks, Roger. Thanks for having us here. Thank you.