Allogene Therapeutics, Inc.

Good afternoon, ladies and gentlemen. Thank you for standing by and welcome to Allogene Therapeutics' first quarter 2021 conference call. After the speaker's presentation, there will be a question and answer session. To ask the question during the session, you will need to press star 1 on your telephone keypad. If you require any further assistance, please press star 0. Please be aware that today's conference call is being recorded. I would now like to turn the call over to Christine Cassiano, Chief Communications Officer. Ms. Cassiano, please go ahead.

Thank you, Operator, and welcome to our first quarter 2021 conference call. After the market closed today, Allogene issued a press release that provides a corporate update and financial results for Q1 2021. This press release and today's webcast are both available on our website. Joining me on the call today are Dr. David Chang, President and Chief Executive Officer, Dr. Rafael Amato, Executive Vice President of Research and Development and Chief Medical Officer, and Dr. Eric Schmidt, Chief Financial Officer. During today's call, we will be making certain forward-looking statements. These may include statements regarding the success and timing of our ongoing and planned clinical trials, data presentations, regulatory filings, future research and development efforts, manufacturing capabilities, and 2021 financial guidance, among other things. These forward-looking statements are based on current information, assumptions, and expectations that are subject to change. A description of potential risks can be found in our earnings press release and latest SEC disclosure documents. You are cautioned not to place undue reliance on these forward-looking statements, and Allogene disclaims any obligation to update these statements. As a reminder for these calls, we will continue to limit questions to one per person, so we can do our best to answer all questions during the hour. I'll now turn the call over to David.

Thank you, Christine, and good afternoon. We are pleased to provide an update on our progress during the first quarter of 2021, which builds on our exceptional performance in 2020. Just days ago, we celebrated the third anniversary of Allogene. As I've reflected on this milestone, we have many things to be proud of. Most importantly, each and every patient we have treated so far with our allocardy candidates. From the first patients with relapsed refractory non-Hodgkin lymphoma treated with allo501 in 2019 to the start of our first allotumor trial with allo316 earlier this year, we are continuing to define, shape, and advance the field of cardiac therapy. While the initial standards in this field were set by the groundbreaking autologous cell therapies, we are increasingly able to shine a spotlight on the inherent benefits of allogeneic cell therapy and our ultimate goal of improving outcomes for a broader set of patients. Allogeneic cardiac therapies, of course, also come with inherent challenges. We believe our platform is capable of addressing these challenges, and we are proud to continue advancing the depth and breadth of our pipeline our next-generation technologies, and our state-of-the-art manufacturing capabilities. On the clinical front, we are expanding our Allocarchy trials to encompass new targets, new cancers, and new technologies. As we indicated during our last quarterly call, we targeted this year's American Society of Clinical Oncology Annual Meeting for an update on our CD19 program. While Rafael will cover most of what to expect for ASCO during his remark, I would like to note that we recognize the importance of this most advanced allogeneic CAR-T program in the field, and we look forward to discussing not just the data we will present as part of ASCO, but also our broader vision for the program during our virtual CD19 forum on May 19th. I think it is also important to note that while we are still treating and collecting data from our Alpha and Alpha 2 trials to evaluate the full data set prior to next phase, it remains our goal to advance Allo501A to a pivotal Phase 2 trial by the end of 2021. We continue to build on the positive momentum from our presentation of the universal trial at last year's American Society of Hematology Annual Meeting. Interim findings from this ongoing trial demonstrated for the first time that an allogeneic cardiac therapy directed at PCMA can achieve deep clinical responses in heavily pretreated patients with refractory multiple myeloma while eliminating both the need for bridging therapy and treatment delays associated with otolaryx cardiac manufacturing. Our recent regenerative medicine advanced therapy, or RMET designation for allo715, was supported by our proof of concept data. We have continued to execute on our three-pronged anti-DCMA strategy in multiple myeloma. Through our collaboration with SpringWorks Therapeutics, we have started dosing patients in the combination arm of the universal trial to evaluate allo715 in conjunction with SpringWorks' Investigation of Gamma Secretase Inhibitor, Neurogasospat. In addition, we have received IND clearance for allo605, our eagerly awaited first TurboCard candidate, and remain on track to initiate our Phase I IGNITE trial in the coming months. We are excited about the potential of each approach to deliver meaningful results for these patients. I will let Rafael dive into the details of these innovative approaches designed to further advance the potential of allocardial therapy in myeloma. While our initial candidates target blood cancers and follow in the footsteps of autologous cardiac therapies, we have begun to blaze new trails in solid tumors. We are very excited to be dosing patients in the TRAVERSE trial with allo316, which targets CD70 for the treatment of renal cell carcinoma. We believe demonstration of activity in this setting has the potential to accelerate the development of CAR T therapy in siloed tumors and rapidly alter the trajectory of allogeneic CAR T and look forward to executing this study. From our first day at Allogene just three years ago, controlling our own manufacturing has been core to our vision of ensuring that our therapies are available and accessible to eligible patients within a matter of days. Under the skillful leadership of Dr. Alison Moore, our Chief Technical Officer, we are well on our way of achieving that goal. We believe producing our Allocardia therapies at Cell Forge One our state-of-the-art manufacturing facility in Newark, California, will allow us to scale production, control costs, and equally importantly, continually improve and enhance the quality of the output. We have begun engineering runs at our new facility and are on track to initiate GMP production later this year. As we execute towards a new vision for CAR-T therapies, one that allows us to embrace the inherent benefits afforded to an off-the-shelf therapy, the ability to treat every eligible patient, the ease with which to consolidate therapy or even re-dose patients, the potential to extend access into community setting, and the possibility of making therapy available to patients with follow tumors. We are excited about what is to come, and the role we are playing in redefining the future of this therapeutic modality. I will now turn the call over to Rafael for further updates on our research and development activities. Thank you, David. Our research and clinical teams have been pursuing numerous projects, all aimed at strengthening our current AllocardT pipeline and platform while preparing to meet future challenges associated with extending the potential of allogeneic cell therapy. Last week, we were pleased to announce that we will be presenting updated data on the Phase I Allo501 study together with initial results from our Allo501A study at ASCO. The update on Allo501 will include longer-term follow-up from the 22 patients that were initially reported on at ASCO 2020. In addition, we will provide information on additional patients treated subsequent to ASCO 2020 with a particular focus on CAR-T naive patients. As part of this readout, we do intend to break down responses between follicular lymphoma and large B-cell lymphoma. Initial data from 501A alpha-2 trial will report on the phase 1 dose escalation portion of this trial. Recall that the alpha-2 dose escalation phase was designed to quickly confirm that the findings seen with allo501 translate into allo501A prior to advancing this construct forward into a potential pivotal phase 2 study. For that reason, this trial focuses on a homogeneous large T cell lymphoma patient population. Dose escalation was completed late last year, and as such, the duration of follow-up will be limited in the alpha-2 trial. More recently, we have begun treating patients in alpha and alpha-2 under our consolidation dosing protocol. This regimen allows patients who have not progressed after an initial dose of therapy to receive a second scheduled administration of CAR T cells with the goal of improving or extending their response. Our ASCO presentation will include results on the first few patients treated with consolidation therapy, although the duration of follow-up will, as a result, be shorter. ASCO will also feature a separate presentation on the safety and biomarker data on Allo647. As you are aware, Allo647 is a key component of our platform. and we believe that it enables a differentiated approach to lymphodepletion in our trials. We look forward to reporting data across our CD19 program later this month. Given that ASCO meeting is just weeks away, we will not be discussing any further details between now and the presentation, but do hope that you will join us at our CD19 forum on May 19th. The structure of ASCO as a virtual meeting will allow us and a select group of clinical trial investigators to discuss the full set of clinical results being presented at the conference and provide the allogene team an opportunity to share our vision for the future of allogeneic heart disease therapy. As David mentioned earlier, we're pleased with the progress we've made across our multi-pronged BCMA strategy for relapsed refractory multiple myeloma. Our most advanced program is ALO715, which received RMAT designation by the FDA following updated proof-of-concept data presented from the universal trial last year at ASH. We continue to enroll patients in this trial, and as we announced a few weeks ago, we have begun treating patients in the combination arm of the study, which is evaluating ALO715 in combination with Neurogastastat, an investigational gamma secretase inhibitor being developed by SpringWorks Therapeutics. last month we also announced progress on the third prong of our myeloma strategy with ind clearance for allo 605 our first turbo car candidate we are very excited about allo 605 as we prepare to launch the phase 1 ignite trial and learn more about how this proprietary next generation technology performs in the clinic as you may recall turbo cars are designed to provide selective programmable cytokine signaling to CAR T-cells in order to counter T-cell exhaustion, improve T-cell function and potency, and potentially reduce cell dose requirements. Should Allo 605 demonstrate the benefit of this technology, we would look forward to the potential of applying it across our platform. We feel confident in the approach we're taking to maximize the benefit rates of allogeneic cell therapy and hopefully our ability to deliver a much-needed alternative to patients with multiple myeloma and who progressively failed treatment. Lastly, but definitely not least, we're excited to extend our Allocard T platform into solid tumors. Earlier this year, we began dosing patients in our first solid tumor trial with Allo316 targeting CD70. The traverse trial is enrolling patients with advanced or metastatic renal cell carcinoma, and it's designed to explore various Allo316 cell doses. The endpoints being assessed are safety, tolerability, depth and duration of lymphodepletion, cell expansion, and antitumor activity. Given the high prevalence of RCC and the lack of new treatment modalities for patients with advanced disease who have failed standard therapy, we look forward to working closely with leading kidney cancer centers and cell therapy specialists to explore allogeneic cell therapy in patients with renal cell cancer as a potential meaningful treatment option. Beyond this trial, we are leveraging internal innovation to expand the utility of our turbo car technology platform to address specific biology, namely that of tumor microenvironment in solid tumors. Preclinical data presented at the 2021 American Association for Cancer Research Annual Meeting demonstrates the ability to engineer inducible turbo cars, which confer cytokine signaling upon binding to PD-L1 and PD-L2 in the tumor macroenvironment, or when stimulated with an anti-PD-1 antibody. In addition to supplying cytokine signaling, these turbo cards are designed to enhance the therapeutic index of allocard T cells within an immunosuppressive solid tumor microenvironment. As our clinical work proceeds, we remain committed to our deep pipeline and broad research to make allogeneic CAR T therapy the modality of the future. And now, I'd like to turn the call over to Eric to review financials.

Thank you, Rafael, and good afternoon, everyone. During the first quarter, we made substantial progress in setting up our China joint venture, Aloe Gene Overland BioPharm, by establishing governance and building corporate infrastructure. Financially, we recognized collaboration revenue of $38.3 million in the first quarter of 2021, reflecting the great majority of the upfront payment we had received from the joint venture. We ended the quarter with $964 million in cash, cash equivalents, and investments. In the first quarter of 2021, our research and development expenses were $55.2 million, which includes $7.9 million of non-cash stock-based compensation expense. General and administrative expenses were $16.4 million for the first quarter of 2021, which includes $8.9 million of non-cash stock-based compensation expense. Our net loss for the first quarter of 2021 was $33 million, or 25 cents per share, including non-cash stock-based compensation expense of $16.8 million. As mentioned last quarter, we expect to support five clinical trials during 2021, including the start of a potentially pivotal trial for Allo 501A. We're also looking forward to initial GMP production at our Newark manufacturing facility, known as Cell Forge 1, which will require substantial incremental investment in R&D. We continue to expect full-year GAAP operating expenses to be between $300 million and $330 million, including estimated non-cash stock-based compensation expense of $80 million to $90 million, and excluding any impact from potential new business development activities. With that, we will now open the call for your questions.

Thank you. And as a reminder, to ask the question, you will need to press star one on your telephone. To withdraw your question, press the pound or hash key. We do ask that you please limit yourself to one question. Our first question is from Salvin Richter with Goldman Sachs. Your question, please.

Good afternoon. Thanks for taking my question. As we look to this CD19 event around ASCO and you look to all the levers to get a whole understanding on the go-forward pivotal study. How do we think about whether there's enough information on consolidation and 501A to get a picture of what the go-forward is, or do you think that will take more time to evolve just given the durability that you mentioned earlier on when these trials started?

Good afternoon, Sabrin. David Chang here. And let me take that question and also I may ask Rafael to chime in a little bit. Certainly, you know, the questions that you are asking are very important. On the other hand, we are very close to May 19th when we are planning to have the CD19 day where we will detail all this information. Throughout the development of 501 and 501A, we have been carefully advancing the program, asking many important questions, including the cell dose, and also trying to optimize the lymphodepletion, which we believe is very important to allow allogeneic CAR T cells to function. And then also, given the uniqueness of allogeneic in terms of the benefits that it comes with redosing and others, we also investigated redosing, including the consolidation, which is sort of the later regimen of how we are investigating different levers. So, you know, from all these things, the way that we are envisioning is the 501 study, which has been going on for the longer period than the 501A, That study, you know, most of which is based on a single dose of LO501 cells, will give the most informative data set on the durability of the response. And then when it comes to the 501A, as we have said in the prepared statement, the primary objective of the 501A study is to make sure that 501A behaves similar to 501, and also we layered additional question of whether the consolidation can deepen the response. I think there are many different information that will be included in our CD19 presentation. For that reason, we sort of went out of our way to have the CD19 day where we can really detail the complexity of the data that may not be so apparent in simple scientific presentations. Sabin, I know that I did not directly answer the questions, but I feel pretty confident that as we have done in our other presentations, we will provide very informative set of data in our CD19 day.

Thank you. Thank you. Our next question comes from Mark Fram with Collin and Company. Your question, please.

Hey, thanks for taking my questions. David, as you just mentioned, one of the big kind of unknowns, right, is the durability of the responses we saw last year and, you know, that the, that ALO501 can generate. So when you focused on the kind of higher dose of ALO647 going forward, I believe there's eight patients a year ago with that, with that dose. Who'd be thinking about that being the, the bulk of, you know, determining that durability or is there really, you know, a large number of patients coming forward? And then, you know, when we think about comparing it to autologous, should we really be looking at, you know, the reported, you know, the potency of the cells with the reported kind of durable response rates on the kind of modified intent to treat basis that they tend to be reported on? Or do you think we need to look more holistically at kind of the overall treatment process?

Mark, thank you for asking those important questions. First of all, in terms of how to best assess the durability, I suggest that we wait until the CD19 date. But at the end, when it comes to durability, we'll be presenting all the available data, including the patients that were part of the ASCO 2020 presentation. as well as additional patients that we have treated since. In Allo 501, you know, this has been a really, you know, great opportunity for us to learn so many different aspects of allogeneic cell therapy that we didn't know of. And, you know, with the number of patients that we have treated, we have a lot of confidence about the data set that we have generated. So on that, let's hold off on a little bit. You know, the second question of, you know, ITT versus MITT, this is a very important question. And, frankly, this has been a part of ongoing debate in the cell therapy field from 2016. I remember the AACR meeting when Crystal Marco asked a question about, you know, questions about, you know, whether MITT is the right way to assess the benefits of CAR T therapy. And since then, we have gone a long way. And as we advance the allogeneic CAR T therapy, we feel that there is an opportunity to correct that sort of, you know, incorrect use of MITT to assess the clinical benefit to more robust ITT assessments. So I think this is an important aspect, and we will gradually sort of try to educate the field the value of assessing the treatment benefit based on ITT, not just MITT. So that will be an ongoing process. And during the CD19 day, we will talk about that topic a little bit.

Okay. Thank you.

Thank you. Our next question comes from Kelly Shi with Jefferies. Your question, please.

Hello. Congrats on the progress and thank you for taking my question. My question is also regarding the consolidation regimen in alpha trial. I want to confirm, so far all the patients have been treated with two doses at 120 million cells. And also, do you have a plan to actually increase the dose with the new information? And are we going to have data of T-cell dynamics and biomarker studies for redosing cohort at ASCO? Thank you.

Kelly, again, you're asking all the right questions. In terms of number of patients that we have dosed in the consolidation, I'm gonna defer to the CD19 day. But let me ask Rafael to go through the design and the objective of consolidation and what to expect during the CD19 day. We are learning quite a bit from the consolidation regimen. Rafael? Yeah. So the concept of consolidation is really to drive a deep anti-tumor response as possible using a second dose that is scheduled of all of 501, as you know. So any patient who is in a complete response or PR or stable disease at day 28 is eligible to receive this second dose. And you're right, we gave 120 million cells on day zero. And then again on day 30 or so after the scan is done, we gave another 120 million cells. And we're providing this second dose without chemotherapy. And we will sort of enumerate the number of patients that we've been able to do this by follicular and diffuse varsal lymphoma during the C19 day and give you some details as to how that is performing with the caveat that the follow-up is relatively short. I just want to emphasize that the reason why we're doing this is to take advantage of the versatility of allogeneic cell therapy and to see whether, you know, that 60 plus percent of patients that don't benefit in the autologous setting, we can reduce that number using allogeneic therapy. And, of course, in terms of biomarkers, we will have the initial responses, but we will obviously have expansion trafficking, animal residual disease, and some other biomarkers. And I will just finish by saying that we do link for the patients on the consolidation with the second dose, but only with 647, provided that they meet certain hematologic parameters prior to dosing. So you will definitely see this data set on May 19th. Thank you very much. And Kelly, I would also add that from our perspective, in any phase one study, especially with consolidation, the safety of consolidation portion is important, as well as the early read. And early read here will be pretty quick. If there is anybody who only achieved a partial or stable disease with a first cell therapy, can they get to the complete responses with a second cell infusion? There are things that we can figure out pretty quickly, and we will present the number of patients as well as what we are seeing with a consolidation regimen.

Very informative.

Thank you, David. Thank you. Our next question comes from Michael Schmidt with Guggenheim. Your question, please.

Hey guys, I actually had one on the BCMA program. Perhaps if you could comment on how you're tracking in the universal study towards potentially identifying a recommended phase two dose and protocol. And also if you could comment on how the consolidation treatment concept has been incorporated into that study. Thanks so much.

Michael, thanks for the question. As you know, BCMA is an important part of our development program, and frankly, we are making a very exceptional approach towards BCMA by advancing multiple different approaches, including the combination as well as advancing the next generation. In terms of 715, we are obviously very excited about getting the RMIT designation based on the data that we have presented at at ASH last year. And in terms of, you know, the questions, you know, I'm going to ask Rafael, who really has spent a lot of time on the BCMA program to answer the questions. Rafael? Sure. So, Michael, we've continued to those patients in the 715 program. We have, obviously, we're using more than one lot. We're using... different doses, so six for seven, different cell doses. And so that has continued. It's a very vibrant program. Investigators really like it because they don't have to wait. They don't have to bridge. We, as David just mentioned, use updated data from ASH to submit to RMAT, and we're very excited that the agency, you know, view the potential benefit of this therapy. And in parallel, we are executing on neurogazostats, and we are very excited to get started with 605. So all of this is going to be going on in parallel. And the last point that you rightfully made is the consolidation. That is an amendment that we've made to test consolidation in the 715, and we expect to be enrolling on that arm also very quickly. So it's a pretty comprehensive program that goes from the CAR by itself to CAR as an adjuvant neogastrostat, the use of two doses of 715, all the way to the use of TurboCAR technology. And obviously the data will be sequential. We have a lot of data with 715. We will have more by Q4, and we are have given guidance that we will present updated data by Q4. And then as the rest of the data with NERO and 605 accumulate, we will present it, but that may take longer and may go into 2022. So, you know, hopefully this gives you a sense that we are fully committed to this program and you can sort of appreciate the breadth of it. Thank you.

Thank you. Our next question comes from John Newman with Canaccord. Your question, please.

Hi, guys. Congrats on all the progress. Thank you for taking my question. The question is also regarding the universal program. What I'm curious about is, I think you mentioned just a moment ago, Rafael, that you are looking at some different dose levels for 647. I wondered, with regard to Neurogastastat, if you're also planning on looking at different dose levels as well as potentially different dose schedules. I'm just curious if you might explore perhaps giving another dose of Neurogastat maybe, for example, in patients that undergo consolidation. Just curious there. Thanks.

Rafael? Yeah, I mean, we haven't disclosed the doses that we're using of Neurogastat. You know, there's been over 100 patients treated with that product in the Desmoid syndrome that is the development indication for Neurogastastat by SpringWorks. So there's a fairly good understanding of the PKPD parameters and as well as the safety of the product at various doses. So obviously we've been working with SpringWorks to try to determine the dose and schedule and also the durability of treatment as well. All I can say is that we're obviously using doses that we believe are active and that there's dose adjustments based on usual parameters such as safety and so on. But beyond that, we think that we have covered you know, timing that's important to cover for BCMA expression to be as high as possible.

Okay, great. Thank you.

Our next question comes from Corey Casimog with JP Morgan. Your question, please.

Hey, good afternoon, guys. Thanks for taking the question. Wanted to ask on your solid tumor program, alloth-316. So I know this is just getting off the ground, but as we think ahead to future updates and data readouts here, how should we be thinking about the program and preliminary results relative to what you've been able to show in hematologic indications, given this is obviously a little more unchartered territory with a presumably different bar for proof of concept? I guess I'm just wondering if there's any aspects of the data that will tell you kind of to push ahead with what you have versus tweaking the approach. Thanks a lot.

Hey, Corey, you know, that's a great question. And I know, you know, for the past two and a half years, we have focused so much on the hematologic cancer. But, you know, solid tumor, I believe, is where the greatest opportunity is with any innovative therapy. The unmet need there is high. Despite all the advances, cure is rare. And, you know, one-time treatment or, you know, a few times of cell therapy, you know, potential benefit could really change the trajectory, as I've said in the prepared statement about the CAR-T therapy altogether. You know, LO316, that's our CD70 directed CAR-T program. We, you know, prioritize this program based on one thing, which is the expression of the target, which we feel gives sufficient safety margin because a CD70 expression in normal tissue other than some hematopoietic cells is extremely rare. So we believe that this can be safely administered. We have to see that in the clinical trial. And then ultimately, we would like to see whether this works either alone or in combination with the IO regimen in shallow tumors. But before getting to the tumor reduction and others, I think there are many important questions that we need to address. you know, one of which is, you know, how do CAR T cells expand in patients with solid tumor? And we continually ask this question without ever having answered a question about whether engineered cell therapy, how effectively they penetrate into the tumor, and whether once they get there, they elicit the kind of pharmacodynamic response that one would, you know, expect to see. So there are layers of questions that we will be asking, and, you know, frankly, it's This is where the translational research team that we built at Allergen will really play a big role in deciphering, you know, what happens with a CAR-T13 solid tumor. So, you know, we are very excited about advancing this. And, you know, 316, you know, while we are initially targeting renal cell, you know, this is a, you know, target that can potentially have utility in many different indications, solid tumor indications, as well as heme malignancies. So, you know, stay tuned. And we just started the study. Hopefully, you know, by early next year, you know, we will be able to update you as well as the rest of the field about how our CAR-T program is doing in solid tumors. And certainly as going forward, we will be, you know, putting more emphasis on solid tumors. I think there is, you know, such great opportunities. Great. Thanks, David.

Very helpful.

Thank you. Our next question comes from Luca Eze with RBC Capital. Please go ahead.

Hello. Thanks so much. Congrats on all the progress here. Maybe I want to circle back on Mark's question earlier. I think last time I checked, Zuma won the CR six months, was 33% on an ITT base and 36% on a modified intent to treat population rate. Are those the right benchmark that we should have in the back of our mind as we see this data? And maybe related to it, should the data be a bit shy of this number? Do you think that some docs will still be willing to maybe compromise a bit on efficacy for all the benefits of allogeneic? Maybe for those patients where autologous is simply not an option. Any call there would be great. Thanks so much.

Luca, I mean, I have to say we are asking the same questions and we are actually not beginning to ask the physicians about these questions. But, you know, let me ask Eric, you know, to put more color to the response to your question. Eric?

Yeah, thanks, Luca. I mean, certainly appreciate the question and your interest in our views here. I honestly think that our May 19th CD19 Forum is answer that question in the context of the actual data and how we size things up relative to the autologous products. So, you know, we'll have a lot more to say then. I do think your ITT and MITT analyses and numbers are in the right ballpark, so we see things, you know, pretty consistently. But I think in terms of laying out the strategy and where we're heading in this field and in particular trying to maximize all the benefits of all the off-the-shelf characteristics of an allogeneic product, we're best positioned to talk about that stuff then.

And, Luca, I would say one other thing, which is, you know, one of the things that we are trying to achieve with the allogeneic cell therapy is trying to treat every eligible patient, you know, which is something that Ocala's cardiac therapy has not been able to do. And as you treat every eligible patient, I mean, certainly, you know, this is really moving the, you know, bar to the, you know, ITT analysis rather than, you know, simply compromising the efficacy analysis using the modified intent to treat.

Got it. Thanks so much. Super helpful.

Thank you. Our next question comes from Mark Braden back with Oppenheimer. Your question, please.

Hey, thanks for taking my question. I certainly appreciated Raphael's earlier comment that you'll be breaking down response analysis in the alpha study by tumor histology. I'm just wondering if patients who are enrolled into the alpha study more recently were in any way enriched for large B-cell lymphomas, or if the proportion of patients with indolent versus more aggressive NHL will be more or less the same as what we saw last year at ASCO.

Okay, so, you know, Rafael, you know, this is something that, you know, I'm going to ask Rafael to respond. You know, one thing I would say is we're not going to go too much into specifics about the population, but we can give you a general sense of what's going on between these two studies. Yeah, I mean, I would simply say that we will have a – a sizable population of both histologies. So unlike GARASCO in 2020, we actually have fewer patients and it was harder to actually scientifically make any kind of conclusions. Now we've accumulated more patients and we'll be able to separate them by histology and get the data that way. So you should expect to see it analyzed both ways. As you know, the 501 study allows entry of both histologies, whereas 501A is only large piece of lymphoma because that's the product that we intend to commercialize. So, you know, we obviously, when we get patients, we follow algorithms to try to decide in which study to put them on. But in terms of numbers, I think, you know, as you will see on May 19th, we'll be able to show a good representation of both.

Okay, fair enough. Looking forward to the 19th.

Thank you. Our next question comes from Ben Burnett with Stifel. Your question, please.

Hey, thank you very much for taking our question. You guys are holding the ILO 501 company event on the day that ASCO abstracts are released. I think this is clearly something that we're all looking forward to, but this is also, I guess, just a bit different from how you've held these types of events in the past, where I think these events were held more in line with the actual presentation at the medical meeting. So I guess just curious, why hold this event so early before the ASCO meeting? Sure.

Ben, thanks for that question. I mean, you know, obviously, you know, times are quite different, you know, with virtual meetings being the norm and we're learning, you know, as we sort of prepare for each of the meetings. So, you know, this is something that we had given some thoughts before taking this direction. But let me ask our Chief Communications Officer, Christine, to respond to your question.

Hi, Ben. I'm actually really happy that you asked this question because we have been getting it a lot. So, you know, everybody thinks of the meeting and when you're there in person, it's very different. But with ASCO being virtual again, not a lot of people realize that the embargo lifts actually on all data when the abstracts come out. So you have the, you know, companies have the option to just focus on the abstracts or actually release all data. So I we decided that we would take the opportunity and kind of take the advantage of the opportunity to stay out of the rush of the full conference activities and host our event on the 19th so we could dedicate a substantial amount of time to what will give us the full update on the program.

Okay. Okay. I appreciate your thought process there. Thank you.

Thank you. Our next question comes from Dane Leon with Raymond James. Your question, please.

Thank you for taking the questions, and congratulations on all the progress. I want to ask a question actually on the turbo car program. Maybe it hasn't been discussed as much, but you are moving into clinical studies, which is exciting with 605. So the question is, we have not really a a one-for-one comparison, but we do have some idea about utilization of AutoCAR-T in the CD19 space with PD-L1 via the Zuma 6 study and some others. I just wanted to get your thoughts in terms of how your team was designing the program, designing the cars, how you thought about safety components. Generally, it seems like the sequencing or actual overlap of use of PD-L1 in the setting of at least auto CE19 car T has been acceptable. But, you know, there have been some events, although you can't really figure out what, you know, whether it was the auto car or the, you know, Tesla's map in Zoom 6. So I just wanted to get your thoughts in terms of how you think about the safety component of that design and what your team specifically, you know, considered in that design of the construct. Yeah.

Now, Dane, thanks for, you know, asking all these important questions. I mean, you know, in terms of safety and in terms of seeing what happens with turbo, I mean, every time when you're doing something that has been done, I mean, there's a lot of unknowns, and we are doing this in a very carefully, you know, orchestrated manner. I mean, the first program, the LF605, It is what we would consider as a relatively straightforward, simple version where we are just providing the cytokine stimulation that is programmable to the cell. And so the signal only goes to the CAR-T positive cells. And this is really to enhance the fitness of the cell. by providing signal three as part of the activation process. And, you know, preclinical results have shown that these cells are much less prone to become exhausted. And also in the xenograft in vivo animal studies, not only we reduce the size of tumor, we eradicate the tumor, which is something that's very rare to see in the cardiotherapy setting. At AACR, you know, we also presented a newer version that we are sort of in the process of designing. And this is where, you know, we are trying to leverage the science and the technology that is behind TurboCAD to potentially use the negative signals, such as PD-L1 or even TGF data negative signaling, and turn that into a positive signal to the cell. So, in effect, it provides two ways to make the CAR-K cells work well in cell tumor. One, it provides the cytokine signaling. And two, it has a potential to neutralize the negative signals in the tumor microenvironment. So, this is a work that the team that Barbara Sassou, our CSO, has been really leading. And, you know, we are sort of beginning. You know, we will first find the initial data from 605, and there's a lot more to come with this platform-based technology. So stay tuned. Thank you.

Thank you. Our next question comes from Rainey Benjamin with JMP Securities. Your question, please.

Hey, good afternoon, everyone. Thanks for taking the questions. I guess I'd love to get a little bit more color or an idea of the biomarkers that you were looking at for allo647. Is this primarily, you know, concerning patient selection or why, you know, why is that a focus as part of that poster presentation? And at the risk of, you know, the answer being, oh, it's way until May 19th, if I could follow that with a totally separate question regarding consolidation. Have you thought about maintenance therapy especially given that the second dose of consolidation doesn't have chemo. Any thoughts regarding maintenance therapy going forward?

Well, you know, I think I should hire you to be part of our research and development team. You're asking all the right questions. Rafael, I mean, we've been talking about this constantly, so I'm going to let you, you know, take Ren's questions. Yeah, Ronnie, these are both really good questions. I mean, with regards to 647, it's actually a really interesting, I think, data set that, you know, we've been able to accumulate with all these patients. So first of all, we look at the ability of 647 to cause T cell depletion. And this receptor, CD52, is not supposed to be on hematopoietic precursors other than T cell precursors. And so we know that the deeper and the longer the duration of T cell depletion, the lower the ability of the patient to actually be able to reject our cells. And we need a duration of expansion as well as persistence for the cells to actually be able to attack the tumor and eradicate it. So knowing this correlation between PK and pharmacodynamics, in this case being T cell, we are, you know, we are able to actually fine-tune this dose. And so this correlation also is made with expansion of the cells. So this is really important because CD52 depletion is kind of the cornerstone of our ability to be able to use autologenic cell therapy and prevent rejection. So the next biomarker we look at is do the cells actually expand and do they persist? we go from those to T cell levels to expansion. And then ultimately we correlate that with clinical outcomes. And so this is sort of the series of basic biomarkers that, you know, we, we are doing. Obviously we've been doing this with single cells and we are now doing it in the consolidation arena that, you know, that we, we have spoken about before. And then in terms of chronic therapy or maintenance therapy, I mean, this is something that we haven't really gotten into yet. We are in sort of the first forays of consolidation, and we will see what that shows us. And then, you know, we'll eventually make a decision in terms of what we believe is the best doses and schedule to go to phase two. You know, I would also add, I mean, you know, Rafael, you know, had made a comment. In the consolidation portion, we only limpo deplete with allo-647, you know, without using chemotherapy. This is something very unique. And, you know, that kind of decision is based on the PK-PD analysis of what we have seen so far. And, you know, the question around whether we are moving towards patient selection, I think that's just a little bit too early. I mean, you know, I don't think, you know, that's really the goal of this kind of analysis. I mean, you know, the goal of, you know, this analysis, you know, how to best use the 647 for the intended purpose of lymphodepleting safely and appropriately.

Got it. Thank you very much.

Thank you. Our next question is from Rahul Prasad with William Blair. Your question, please.

Thanks for taking the question, and congrats on the progress. I have a quick question on the RMAT designation for 715. Does that encompass the neurogastro-step arm, and how are you going to approach or use the RMAT designation in kind of advancing that arm of the trial. And then just kind of on a regulatory as a kind of a Part B question, how should we think about maybe applying for designation for Allo 501A? Are you waiting for maybe the consolidation therapy and maybe moving into Pivotal before applying for that? Thanks.

Rafael, you want to take that question? Sure. So I think the arm of Our designation for 715 encompassed primarily the data that was presented at ASH with some updates. Obviously, we were delighted to see that the agency recognized the value of the product, particularly at the higher doses where we saw significant efficacy, including BGPR and complete responses and MRD negativity. And so we had, obviously, some additional follow-up, and I'm not going to go into all the discussions that took place between the agency and us as the sponsor in terms of requests and so on, but they were satisfied that this was a product that merited this designation. We intend to take advantage of this designation, obviously, as we move forward with BCMA development. With regards to 501A, we started that program later, as you know. We have more data with 501, but 501 is not the product that we intend to develop, so therefore we're not seeking ARMA designation or other designations with 501. We would seek it with 501 , as you rightfully said, but we started the dose escalation late last year, and then we finished it. The follow-up is not as long, and we started consolidation relatively recently. So, we believe that it's better to get a little bit of maturity in the data and then go in, but we will be seeking designation as well. And, you know, whether we do it before the phase two or not, you know, that's a decision that we need to make based on the data that we see. But, you know, I'm always thinking that the sooner that we do this, obviously, the better. But we'll have to make sure that the data warrants it, and that will take a little bit of time for the data to mature.

Great. Thank you.

Thank you. Our next question comes from Asika Gunawardena with Troy Securities. Please go ahead.

Hi, guys. Thanks for taking my question. So I just want to get a quick sense check here. There's data to suggest that deep upfront response may be a key driver of durability in large cell. So I just want to get your thoughts as to where do you think there's data in the public domain that also suggests that this is also the case in follicular lymphoma Or is persistence more important in this setting? And then just a quick follow-up. I just want to confirm, Rafael, did you say that we will see MRD negative data at the CD19 day? Thanks so much, guys.

In terms of the deep response, I mean, I think that's, you know, based on, you know, basic principle of, you know, the cancer treatment. You know, more cancer cells that you kill, you are more close to, you know, potentially eradicating. So, you know, the field really has moved from, you know, the concept of just, you know, controlling progression, i.e., you know, maintenance to a more upfront. And, you know, whether, you know, the behavior of large B-cell lymphoma and follicular lymphoma is going to turn out to be the same or somewhat different, I think, you know, we need to wait a little more for the FelixoLymphoma data set to mature, you know, because the study that was done by Kite, the data, you know, time difference is about three years. So I think, you know, time will tell. But, you know, as an oncologist, you know, I do have, you know, this conviction that the more tumor cells that you kill, more likely that you will have a doable response. MRD response, Rafael, do you want to comment on that? Yeah, we've been following MRD response on an ongoing basis on our lymphoma program. As you know, it's not a standard as it is obviously in leukemia or is in myeloma, but we have that data and we will share with the rest of the biomarker what the MRD data is to date.

Great, thank you very much.

Thank you. Our last question is from Rob Burns with HC Wainwright. Your question, please.

Hi, this is Mark speaking on behalf of Rob Burns. Thanks for taking my question. In anticipation of the update from the universal trials, I think 715, I was wondering if you could provide any indication as to whether the higher dose 715 plus score 7 cohort is showing an improvement in response versus your data at the previous conference.

Yeah, Rob, you were a little bit, you know, wasn't coming clearly, but I think the question is whether the 715 at higher dose with a higher lymphodepletion was providing better response You know, we covered a little bit of that aspect during the ASH presentation last year, and certainly more investigation is ongoing. And we will update the data as in the next opportunity that we have, which we project will be more towards the end of the year.

Thank you.

Thank you. And this concludes our Q&A session. I will pass it back to management for any final remarks.

All right, thanks. As we close out the call, I would like to thank everybody who joined us today as well as our teams at Allogene and our many patients, investigators, and collaborators. As we talked about numerous times during the call, please join us on May 19th for our virtual C19 Forum. We look forward to seeing you then. Operator, you may now disconnect.

Thank you. Ladies and gentlemen, thank you for your participation in today's conference. This does conclude the program, and you may now log off and disconnect.