Good afternoon, everyone. Thank you for joining us for another session at the 41st annual J.P. Morgan Healthcare Conference. My name is Brian Chang. I'm one of the senior biotech analysts here at the firm. Presenting next is Allogene. With us today, we have president and CEO of Allogene, David Chang. I'll turn over the stage to David, and then the presentation will be followed by a Q&A session. Thank you, Brian, for hosting us. Thank you for those who are in the audience. I will be making some forward-looking statement, which will be subject to the disclosures we have in the SEC filing. Allogene is really here to democratize the cell therapy. Our mission is for the patients. We have six foundational platform from AlloCAR T, Turbo CAR-T, Cloak & Dagger, manufacturing, as well as iPSC programs to fuel the innovation. Also, we distinguish ourselves by having treated over 175 patients with AlloCAR T across four different programs, which is generating wealth of the data, both clinical as well as translational science data for us to make decisions on different programs that we are advancing. We ended 3rd quarter of last year with $637 million, which gives us enough cash runway to do what we set out to do. In that regards, we are one of the unique companies in the allogeneic CAR-T, where we have a singular focus of advancing allogeneic CAR-T. With that, we have the industry's first potential pivotal phase 2 allogeneic CAR-T studies that were initiated already. Now the much of the, you know, focus of the company is really shifting from, you know, pipeline advancement as well as learning about the allogeneic CAR-T through various optimization to execution of the pivotal study. You know, with that, I'm pleased to announce that we added Zach Roberts to the management as the head of R&D. Zach comes with a wealth of experience in the cell therapy, especially we have worked together as we advanced many ZUMA trials while we were work at Kite Pharma. He comes with not only the execution experience, but also knowledge of the field as well as the close contact that he has with the investigators. This slide is really to highlight, you know, what's happening with the CAR-T therapy. It has been five years since the first approval of CAR-T therapy. Now in 2022, not only we are seeing the tremendous clinical benefit but also seeing the commercial success. The revenue in 2022 is expected to be, you know, over $2.5 billion. By 2030, the CAR-T-related revenue is expected to surpass $10 billion. What's also shown on this slide is number of patients that were treated with autologous CAR-T in each year. 2022, we expect that to be about 6,600 patients. That relative to patient incidents for the approved CAR-T indication, where there are available patient number of 64,000 only represents little over 10% of the patients receiving the therapy. As we look to the future, there we expect the demand of CAR-T to grow as the companies advance the CAR-T trials to the earlier lines. However, the bottleneck that exists in the autologous CAR-T will limit the access of the therapy to the patients. The number, the patient who will have access to the CAR-T therapy, we expect to remain at about 10%. This is what allogeneic CAR-T therapy is really coming here. What's shown here is the difference that exists in the current autologous CAR-T therapy, where the treatment is more or less a personalized therapy. That comes from the fact that autologous CAR-T, each manufacturing can only treat one patients. Each manufacturing also comes with a complex logistics, not only having to manufacture the cells, but also scheduling, leukapheresis the patients, and all the ancillary costs and the complexity that comes with a personalized therapy. AlloCAR T is set out to address these issues by advancing the field to pharmaceutical product level, where from each manufacturing run, we can produce enough materials to treat hundreds of patients. Also by doing that, so, you know, eliminating the complexity, the complex logistics of the autologous CAR-T therapy. This is what we set out to do, which is really democratizing the cell therapy, which is really needed to grow this field. The field of redirected cell therapy is also evolving, not just between, you know, autologous and allogeneic, but also with the entry of the bispecifics. The way that we see the value proposition of allogeneic CAR-T comes from the fact that allogeneic CAR-T comes with a high-end efficacy, availability on demand, as well as one-time dosing. This is a unique differentiation of the allogeneic CAR-T that cannot be done with autologous CAR-T or bispecifics. Let me talk a little bit about the response rate, especially the durability allogeneic CAR-T, which has been questioned for a number of years. What's shown here is the swimmer plot. Each lane represents one patient experience. Here, we have 14 patients who achieved complete remission in our phase 1 studies. At the initial data cut in 2021, 10 of the 14 patients were in complete remission. When we did a follow-up study a year later, so this is essentially data cut in October of 2022, what we are seeing is out of those 10 patients in response, nine continue to be in complete remission, and most of them, in fact, all of them, having surpassed the 12-month time point. I think this is really highlighting the fact allogeneic CAR-T can bring the same level of efficacy that changed the field brought out by the CAR-T. What's enabling that remarkable efficacy, we believe, is the proprietary ALLO-647-based lymphodepletion. What's shown here is the relationship between ALLO-647 exposure and the likelihood of response shown on the right. In the clinical study, phase 1 study, we have tested three different doses of ALLO-647. As ALLO-647 goes up to the higher level, the exposure goes up, and so does the likelihood of the response. This is actually the regimen, lymphodepletion regimen, that we will be using forward in the pivotal studies that are ongoing. What does that translate in terms of the overall pipeline? We have a wealth of different programs covering both hematologic cancers as well as solid tumors. Starting with the hematologic cancer, we have CD19 program, ALLO-501A, which is entering in a pivotal study. It's ALPHA2 study. The second study, EXPAND study, that is designed to demonstrate the contribution of ALLO-647 as the critical lymphodepletion components. Both of these are potential pivotal studies that will allow the approval of ALLO-501A as well as ALLO-647. I'll talk a little bit more in details about those two studies. In addition, we are in the planning phase for the earlier line study, which we have named as ALPHA3, and we will communicate the plans towards the end of the year. We also have the next generation CD19 program that will potentially take the field to a different level. Following CD19, we have programs in the BCMA for multiple myeloma. The lead program is ALLO-715, and the second one that is being investigated is ALLO-605 that utilizes the Turbodomain as a way to enhance the activity of CAR-T. We also have additional program targeting CD70 as well as FLT3 for potential indications in T-cell leukemia and lymphoma and acute myelogenous leukemia. On the bottom is shown the solid tumor programs, starting with CD70, ALLO-316. This is already in the clinics, being studied in the renal cell cancer. We have additional programs in the preclinical phase targeting DLL3 and Claudin 18.2. I'm gonna walk through each of the three key programs, ALLO-501A in non-Hodgkin lymphoma, ALLO-715 in multiple myeloma, and ALLO-316 in renal cell cancer. Starting with ALLO-501A. What has been done over the last 2.5 years is really optimizing the parameters to best utilize ALLO-501A in allogeneic CAR-T setting. That included exploring the lymphodepletion regimen, which led for us to conclude the best regimen is FC plus 90 milligrams of ALLO-647. We also explore the cell dosing as well as different manufacturing process. All that's leading is summarized on the right side, where with ALLO-501 or ALLO-501A, manufactured with Alloy process, producing overall response rate of 67% with a 58% complete remission rate using the FCA90 as a lymphodepletion regimen. Also, in this case, 50% of the treated patients remain CR at both six and 12 months. All this is coming with a manageable safety profile, no dose-limiting toxicity, graft-versus-host disease, or neurotoxicities. Also, the incidence of cytokine release syndrome is only at the low grade. Now, how does this compare with what has been reported with CAR-T is shown here. Walking each column, what is shown is all the patients that we have treated with the Alloy manufacturing process. Next to it is subset of those patients who have been lymphodepleted using FCA90 and receiving 120 million cells of ALLO-501 or 501A. Next to that is three datasets coming from approved autologous cell therapy, Kymriah, Yescarta, and Breyanzi. Going from top to bottom, when you look at the overall response rate, complete remission rate, or complete remission at six months, which is a very important landmark analysis. What is being seen with ALLO-501A is very comparable to what has been reported with CAR-T. Safety profile is also very similar. I would argue, if anything, the rate of cytokine release syndrome and neurotoxicity events is on the lower end of what has been repeated with autologous CAR-T. Does the infection rate, grade 3+ infection rate, we have seen between 8% and 15%, whereas in the CAR-T studies, reported rate ranges somewhere in the 20% range. Another important point that I wanna make in this slide is the number of patients who are enrolled in the study who are able to receive the treatment. In our study, essentially all enrolled patients, all but one patients were able to receive the treatment. Whereas in autologous, due to the manufacturing and manufacturing delays, the number of patients who can actually receive the intended treatment, you know, range between lower end of 64 to the high end of 91%. This is really what differentiates autologous CAR-T from allogeneic. We have looked at the data in a somewhat different way, you know, following the Kaplan-Meier curve. This is looking to see when the patient progresses. This is a little bit of a busy slide because three Kaplan-Meier curves representing CAR-T therapy data are overlaid with what we are seeing with our CAR-T program. Despite the complexity, one clear picture is that Kaplan-Meier curve allogeneic CAR-T therapy is overlapping what has been reported with autologous CAR-T. At this point, we believe our program is sufficiently de-risked with a high likelihood of reproducing the tremendous efficacy that has been seen with CAR-T therapy. The planned pivotal studies are outlined here. The first one is ALPHA2 study. This is a single-arm study that will use FCA90 as a lymphodepleting regimen. Everybody will receive a single dose of ALLO-501A using the primary endpoint of objective response rate and complete remission rate. We intend to target approximately 100 patients to demonstrate the clinical benefit allogeneic CAR-T study with ALPHA2 study. The second study that's shown below is EXPAND study, where we intend to demonstrate the contribution of ALLO-647 to lymphodepletion in a formal way, in a controlled study, so that to enable the labeling of ALLO-647 as a proprietary lymphodepleting regimen. That study will be using progression-free survival as the primary endpoint. Moving to the next program is ALLO-715. To date, this is the allogeneic CAR-T program that has shown clinical benefit in multiple myeloma. We have shown the, you know, proof of concept, showing the feasibility of advancing CAR-T allogeneic CAR-T program targeting BCMA. Also, we are in the process preparing for phase 2, which can potentially be a pivotal study. What we have seen in this program is a single infusion of 320 CAR-T-positive cells with a lymphodepletion, we call FCA60, can result in objective response rate of 67% with a 42% of very good partial response or better. The program has shown manageable safety profile. No graft-versus-host disease, low grade neurotoxicity, and also low grade cytokine release syndrome. As in the case of CD19 program, ALLO-715 again demonstrated that with allogeneic CAR-T program, we can treat essentially all patients without need of bridging therapy or having the patients wait for the manufacturing of CAR-T. The comparison of 715 data with the approved therapies targeting BCMA is summarized here. ALLO-715 giving the objective response rate 67, very good response rate of 42% or better, and the CR or a stringent CR rate of 17%. I would argue in this small set, data set of 12 patient, that compares very favorably with what has been seen with a bispecific T-cell engager technology, as well as, autologous, one of the autologous, CAR-T Abecma. It falls a little bit behind the Carvykti as we have been highlighting. However, we believe that there is an enough opportunity for us to consider potentially advancing 715 into the pivotal stage. This is one of the top priorities of the company as we're beginning 2023. ALLO-316 is our first program and also the allogeneic CAR-T program that has gone into the solid tumor. We advanced this program into the renal cell carcinoma indications based on the existing unmet medical need in the renal cell carcinoma, especially those who have already received anti-angiogenesis therapy together with immune checkpoint inhibitors. Also, you know, the solid tumor targeting CD70, you know, has an opportunity to improve the clinical outcome by the patient selection based on the CD70 expression. This study enrolled as a dose-escalating phase 1 study initially using FCA as the lymphodepleting regimen. Based on some of the cell expansion as well as efficacy data that we have seen, we also added additional lymphodepletion regimen that doesn't involve ALLO-647. Those are FCA and FC. We have treated 17 patients all together in this study, Most patients enrolled in these studies were patients who had previously treated with checkpoint inhibitor and the VEGF inhibitor for advanced or metastatic renal cell carcinoma. What we have seen in this early study, you know, out of 17 patients who are evaluable for efficacy is one pretty significant disease control. Also in the CD70-positive demonstrated, the patients who are demonstrated to be CD70-positive, objective response rate of 33%. Also we have seen that response rate appears to be higher on those patients who have so-called high H-score for the CD70 expression. H-score is really immunohistochemistry-based scores that tells you the intensity of CD70 expression as well as a percentage of tumor cells that are expressing CD70. An example of the responses that we are seeing is shown in this slide. One patient, the patient history, metastatic renal cell carcinoma, you know, involving lungs and also refractory to checkpoint blockade and anti-angiogenesis inhibitor. This is one of the first patients treated with FCA lymphodepletion regimen and treated with a 40 million CAR-T-positive cells. What is shown here is the tumor size reduction, reaching partial response by month one and continuing to have a regression of tumor through month six, showing not only the response but also the durability of response that can be achieved with the allogeneic CAR-T-cells targeting CD70. Another thing that makes us very excited about, you know, ALLO-316 is the extent as well as the duration of the CAR-T persistence in the blood. What we believe is, you know, contributing to this extraordinary cell expansion is a unique property of the CD70. What we have named as a Dagger that enables our ALLO-316 CAR-T-cells to be somewhat immune from allo rejection by the patient's immune cells. Illustrating that point, this is really if you look at the right side of the panel, what the CAR-T is really designed to do is destroying the cancer cells. The unique characteristics of CD70 targeting CAR is that in addition to going after CD70 expressed in tumor cells, it can go after T-cells that have that are expressing CD70, and that include alloreactive T-cells. In all, this allows the ALLO-316 to be less likely to be rejected by the patient immune system. That we believe is contributing to the extraordinary cell expansion and persistence, as I've shown in the previous slide. To the point that we are considering this approach as a next-generation allogeneic platform in the future products that our research team is advancing. What's behind all this pipeline is our fully integrated, you know, operations technology organization that can handle not only process and analytic assay development, but also product characterization, manufacturing, as well as supply chain management. We have our own manufacturing facility called Cell Forge 1, where we believe at full capacity that facility alone can produce enough materials to treat over 20,000 patients. That is a lot different than what autologous manufacturing can achieve. Looking into, you know, the future of Allogene, where we are is with the CD19 as the best and first-in-class profile entering into the pivotal phase in the third-line large B-cell lymphoma. This will certainly move into the earlier line. Behind that is a BCMA targeting program that we are trying to poise into the potential pivotal study start in near future, and also trying to pay the allogeneic CAR-T into the solid tumor using ALLO-316, as we have shown, I have just shown, the data in the renal cell cancer. In 2023, you know, what are the key events that we are foreseeing? First half, initiation of the EXPAND study in support of potential approval of ALLO-647 in the third-line setting. making a decision on ALLO-715 potential pivotal phase 2 study in relapsed refractory multiple myeloma in the second half. Also updating the phase 1 data on ALLO-316 in the second half in the refractory renal cell carcinoma. you know, completing the phase 3 readiness for the early aligned study of ALLO-501A in the second half. we also project that we will update the long-term follow-up of the phase 1 patients treated with ALLO-501A in the second half of this year. A lot is happening, but in 2023, Allogene as a company will have a singular focus on executing the two pivotal study that we have initiated. We are projecting those studies to complete the enrollment in the first half of 2022, which we hope will pave the path towards the BLA and approval of first allogeneic CAR-T therapy in the CD19 space. With that, I thank you for your attention, and you know, before going to that, I just wanna end, you know, my presentation by reiterating our mission, which is shown on this slide. Create and lead the next revolution in cancer treatment by delivering to patients the first CAR-T products for blood cancers and solid tumors. Our activities really highlights how we are working towards accomplishing this mission. Thank you. Thank everyone for joining us for our fireside chat. We're gonna start the fireside chat now. We have, I think we have runners on the floor if you guys have any questions. I'll start off with a few. The key question that I've been getting from investors is really about differentiation of your platform, right? Just based on where you stand today, you have data from CD19 program in DLBCL. You also have data in multiple myeloma now. Mm-hmm. Where do you see the key differentiation is? Let's say, you know, three years from now, your sales force is in a doctor office. What would their main message be and say, "Hey, this is clearly different than what autologous therapies out there, is, and this is why you should use our product"? You know, great question. I mean, a lot of times, you know, that kind of discussion really becomes the, you know, evidence-based discussion. What I've shown, you know, with the phase 1 study, obviously we have need to reproduce the result in the pivotal study, is that single infusion allogeneic CAR-T cells can reproduce the clinical benefit that has seen with autologous CAR-T. This is a product that is available on demand, that will simplify all the logistical complexity that you have to deal with when prescribing the autologous CAR-T. The same level of efficacy, the convenience, and even without going anything else, being a clinician myself and having to deal with this kind of situation, I think is a really winning proposition. Having said that, you know, my background is R&D, and certainly we are building up our commercial team. As we build a commercial team with the surveys and in, you know, and additional, you know, analysis, we will refine that, you know, core message. I think we have enough materials there to start. Okay. In the indications that you're shooting for, there are a couple therapies that could be in the market. Mm-hmm. before you, which is one of them is bispecifics. Yeah. The autologous cell therapies are also moving into earlier line. Mm-hmm. How do you think where your product fits in into the evolving landscape? Yeah. By the time you get to the market? You know, our primary focus right now is really, you know, eyeing this cell therapy field that's being created by the autologous CAR-T. As one of my slide has shown, the CAR-T is already at $2.5 billion, and it is expected to grow over $10 billion within next 10 years. With that, if we can come up with a product with a value proposition that this is a lot easier to administer to patient because it's the off-the-shelf, and it can reproduce the kind of efficacy that you've seen in the cell therapy, I think that is a very strong argument. Having said that, you know, we are not ignoring the bispecifics. On the other hand, when you look at the number of addressable patients in the non-Hodgkin lymphoma, that's about 150,000 patients. When you also add the multiple myeloma on top of that, you're talking about potentially reaching number that goes to about 300,000. That kind of number allows, you know, multiple products to coexist, and at some point, you know, physicians will come up with how to best utilize, you know, bispecific versus, you CAR-T therapy to maximize the benefit for the patient. Our intent is, you know, make sure that, you allogeneic CAR-T has a good use in there. That's a good segue to our next question. Mm-hmm. Your pivotal phase 2 is ongoing for DLBCL. Is there any specific factor or nuance that investors should know that maybe potentially will give you a boost in terms of the market size, that allow you to say your product is potentially better than what others have shown? Yeah. I mean, I think, you know, the market size increase, I mean, obviously, you know, right now what I see, you know, with autologous is the, you know, growth of the field is limited by the manufacturing bandwidth, as well as the complexity of the administration of the drug. allogeneic by the nature is intent to address those two issues off-the-shelf on-demand therapy that doesn't require patients to be waiting for the cell manufacturing to complete. Also there's all these, complex, you know, logistics, including leukapheresis to generate the starting material, which is how you produce autologous CAR-T. I mean, I think all those things will, you know, from my perspective, I think that's what's really needed for the field to grow and the CAR-T to reach more patients. What's the plan with the ALPHA3? Is there anything that you would like to incorporate in that study to allow you to target the earlier line setting? Yeah. Earlier line for CD19 in non-Hodgkin lymphoma, it's either the second line or potentially high risk front line. You know, there's already approval of autologous CAR-T in the second line, and we are thinking this very carefully. This is a situation that I've learned over many years of doing clinical research. You know, we will come up with a plan, but at the same time, we have to validate the plan with, you know, key opinion leaders and investigators to finalize. Also, our new head of R&D, he is, you know, one person who really champion all the CD19 programs at Kite to move into the earlier line soon. We have a secret weapon behind what we intend to do. Okay. Maybe just one more on CD19. Any updates on the supply from Cell Forge 1 facility? When can that be potentially incorporated into the pivotal study? Any remaining gaining factors that allow you to push that into the pivotal trial? You know, you're asking the question around, you know, yeah, we're using the Alloy process, which is currently being manufactured by the, you know, CDMO. Our intent is to bring the manufacturing into more under our control. It can be done in various different ways, but one of the plans include bringing the manufacturing. It usually is a tech transfer. I mean, it will be the same equipment, same critical supplies that gets used. This is something that we have already done with other products. Our Ops Tech team has a lot of experience in bringing in. It's something that we can do relatively easily, and some plans are already on the way. Okay. maybe switching gears, BCMA. you have two programs ongoing, that have shown data in multiple myeloma. What's the next step? What could we expect in terms of data flow, in the next 12 months? You know, right now with the lead program ALLO-715, you know, I think we have, you know, investigated many different, you know, parameters like lymphodepletion as well as cell dose. Another one that we are carefully reviewing is whether there's any opportunity to tweak the manufacturing to make the cells work a little bit better. That's an ongoing work. On top of that, as we have previously announced, we are engaging the regulatory agencies to understand the, you know, path of approval. That discussion will occur. That's probably, you know, one of the, you know, sort of the facets of how we will make the decision. How does the tweak of the manufacturing play into your regulatory discussions? Yeah. You know, when you know, make some, you know, manufacturing adjustment, it can come as either substantial manufacturing adjustment or just minor adjustment. Minor adjustment is, you know, less onerous. If it's a substantial, you know, adjustment, you're gonna have to show the comparability, you know, analytic comparability. Okay. In terms of the next step, how should we think about what's your preference between the two? You know, that's a, that's a great question. You know, I don't wanna, you know, sort of comment ahead of actually, you know, looking at the, you know, data. I mean, we have to make a decision based on what we see. Let's say, you know, let's just, you know, stay tuned on that one. I mean, as we have said, you know, our plan is to provide a clarity about BCMA pivotal program by midyear next year. Okay. Maybe just one more point on the manufacturing fine-tuning. Are you trying to optimize efficacy? Or is that more for you to start talking to the regulatory agency to line up the pivotal trial? You know, as I said, you know, ALLO-715 falls a little bit below the Carvykti. I mean, there's a lot of sort of, you know, interest in the, you know, manufacturing team as well as development team as, can we do something to close the gap between, you know, what we have shown with ALLO-715 and what Carvykti have shown? There's a lot of, you know, sort of internal discussion around, you know, can you make it work better? Okay. You're working on that? Yeah. Okay. Maybe just, you know, last couple minutes we have. On RCC... Yes. The CD70 target, we saw some initial data just in the fall. How has that data guided your next step for... Let's just focus on ALLO-316 and maybe just looking past ALLO-316 and what you have in DLBC and multiple myeloma. Is your next strategy focus gonna be on heme or solid tumors, h ow should we just think about how the portfolio could evolve over time? Yeah. You know, ALLO-316 dataset that I've shown, despite it being phase 1, you know, result, it is a very significant dataset. I mean, it's the first time that you have shown very convincing way that CD70 targeting CAR-T, and in this case, it's an allogeneic CAR-T, can produce the disease control and up to about 30% response rate. This is, you know, happening while we are still optimizing the cell dose. In the translational aspect of the, you know, phase 1 study, we have seen some very interesting findings such as, The CAR-T cells being actually in the tumor at much higher level than in the circulation, and also CAR-T cells persisting much longer and providing the durability of response as I've shown. Stepwise, like any other phase I study, you know, intent is to decide on the lymphodepletion regimen as well as the cell dose. The next one, I'm gonna split the, you know, conversation in the solid tumor and heme, you know, a little bit later. In renal cell, we have seen that the patient selection can potentially improve the response rate beyond 33% that we're doing, and we already have implemented the patient selection using immunohistochemistry. We also have, using the same approach, expanding the use of ALLO-316 beyond the renal cell cancer into other CD70 expressing solid tumors. That's more or less in the consideration, and obviously there are other things we can do clinically, which is, you know, testing combination with immune checkpoint inhibitor. Mm-hmm. At the same time, it hasn't sort of, you know, we didn't miss the fact that CD70 targeting CAR can have a great potential in T-cell leukemia lymphoma, and also CD70 expressing non-Hodgkin lymphoma, you know, which we estimate it will be about, you know, 60%-70% of, you know, non-Hodgkin lymphoma. The plan, I mean, this is, you know, the strategy evolution that's in work. There is a many opportunities to really expand in a potential use of 316, not only in solid tumor, but also in hematologic malignancies in a very significant way. Okay. Maybe just in our last minute, any updates on ALLO-647 pivotal trial? Are you gear up to start that study? Yes. I mean, there are some sites that are already, you know, activated. The number of patients that we are enrolling in that study is relatively small, 70 patients, and our intent is maintain the enrollment of that study and ALLO-501A study at about the same, so we can complete the enrollment at about the same time. You're trying to show comparability or is it superiority? This is to show the superiority of FCA versus FC, which based on the available data should be a relatively easy task. Great. I think that's all the time we have for today. Thank you, David, for joining us at the J.P. Morgan Healthcare Conference. Thanks everyone as well. Have a great afternoon.