Allogene Therapeutics, Inc. (ALLO) Q1 2021 Earnings Report, Transcript and Summary

Good afternoon, ladies and gentlemen, thank you for standing by, and welcome to the Allogene Therapeutics First Quarter 2021 Conference Call. After the speakers' presentation there will be a question-and-answer session. [Operator Instructions] 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 Amado, 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 this call, 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 built on our exceptional performance in 2020. Just days ago we celebrated the third anniversary of Allogene. As had reflected on this milestone we had many things to be proud of. Most importantly each and every patients we had treated so far with our AlloCAR T candidate. From the first patients with relapsed/refractory non-Hodgkin's lymphoma treated with ALLO-501 in 2019 to the side of our first ALLO tumor with ALLO-316 earlier this year, we’re continuing to define shape and advance the field of CAR T therapy. While the initial standard in this field was set by the groundbreaking of autologous cell therapy, we’re increasingly able to shine a spotlight under inherent benefits of allogeneic cell therapies and our Hosmat call of improving ASCOMS for our broader setup patients. Allogeneic CAR T therapies of course also come with inherent challenges. We believe our platform is capable of addressing these challenges and we’re 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’re expanding our AlloCAR T trials to come with new targets, new cancer and new technologies. As we indicated during our last quarterly call, we targeted this year American Society of Clinical Oncology annual meeting for an update on our CD19 program. While Rafael will cover most of what to expect via ASCO during his remark, I’d like to note that we recognized the importance of this most advanced allogeneic CAR T program in the field and we look forward to discussing not just the data we’ll present as part of ASCO, but also our broader vision for the program during our virtual CD19 form on May 19. I think it is also important to note that while we’re still treating and collecting data from our ALPHA and ALPHA2 trials to evaluate the full dataset, prior to next phase it remains our goal to advance ALLO-501A to our pivotal phase 2 trial by the end of 2021. We continue to build on the positive momentum from our presentation of the universal trial and last year’s American Society of Hematology annual meeting. Interim findings from this ongoing trial demonstrated for the first time that an allogeneic CAR T therapy directed at BCMA can achieve these clinical responses in heavily pretreated patients with refractory multiple myeloma while eliminating both the need for bridging therapy and treatment delays associated with autologous CAR-T manufacturing. Our recent Regenerative Medicine Advanced Therapy or RMAT designation for ALLO-715 was supported by our proof-of-concept data. We’ve continued to execute on our three-pronged and by BCMA strategy in multiple myeloma. Through our collaboration with SpringWorks therapeutics, we’ve started dosing patients in the combination arm of the universal trial to evaluate ALLO-715 in conjunction with SpringWorks investigational gamma secretase inhibitor, Nirogacestat. In addition, we’ve received IND clearance for ALLO-605, our eagerly awaited first TurboCAR candidate and remain on track to initiate our phase 1 IGNITE trial in the coming month. We’re excited about the potential of each approach to deliver a meaningful result for these patients. I’ll let Rafael dive into the details of these innovative approaches designed to further advance the potential of AlloCAR-T therapy in myeloma. While our initial candidates target blood cancers and follow in the footsteps of autologous CAR-T therapies, we’ve began to place new trial in solid tumors. We’re very excited to be dosing patients in the TRAVERSE trial with ALLO-316, which target 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 solid tumors and literally offer the trajectory of allogeneic CAR-T and look forward to executing this study. From our first aid Allogene just three years ago, controlling our own manufacturing has been core to our vision on ensuring that our therapies are available and accessible to eligible patients within a matter of days. Under the skilful leadership of Dr. Alison Moore, our Chief Technical Officer, we’re well on our way of achieving that goal. We believe producing our AlloCAR-T therapies at Cell Forge 1, 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 hospice. We’ve 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 therapy, 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 without patients, the potential to extend access into community setting and the possibility of making therapy available to patients with solid tumor, we’re excited about what is to come and the role we’re playing in redefining the future of this therapeutic modality. I’ll 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 AlloCAR-T pipeline and platform both preparing to meet future challenges of CD 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 1 ALLO-501 study together with initial results from our ALLO-501A study at ASCO. The update on ALLO-501 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 CAR-T naïve patient. As part of this route, we’re doing, bend to break down responses between follicular lymphoma and life T cell lymphoma. Initial data from 501A also do a tile those report on the phase 1 dose escalation portion of this file. Recall that the outset to dose escalation phase was designed to quickly confirm that the findings team with ALLO-501 translate into ALLO-501A prior to advancing this concert forward into a potential pivotal phase 2 study. For that reason this trial focuses on a homogenous large B-cell lymphoma patient population. Dose escalation was completed late last year and as such the duration of follow up will be limited in the ALPHA2 trial. More recently we’ve began treating patients in ALPHA and ALPHA2 under our consolidation dosing product. This regimen allows patients who have not progressed after an initial dose of therapy to receive a second schedule administration of CAR-T cell with a goal of improving or extending the 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 ALLO-647. As you’re aware ALLO-647 is a key component of our platform and we believe that it enables a differentiated approach to include a patient in our trial. We look forward to reporting data for 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 and do hope that you will join us at our CD19 forum on May 19. The structure of ASCO as a virtual meeting will allow us and a select group of clinical trial investigators 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 CAR-T 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. A must attend program is ALLO-715 which received RMAT designation by the FDA following updated proof-of-concept data presented from the universal Cell Forge 1. We continue to enroll patients in this trial and as we announced a few weeks ago, we’ve begun treating patients in the combination arm of the study which is evaluation ALLO-715 in combination with Nirogacestat and investigational gamma secretase inhibitor being developed by SpringWorks Therapeutics. Last month we also announced progress in the third pronged of myeloma strategy with IND clearance for ALLO-605, our first TurboCAR candidate. We’re very excited of our ALLO-605 as we prepare to launch the phase1 IGNITE trial and learn more about how this proprietary next generation technology performs in the clinic. As you may recall TurboCAR are designed to provide selective programmable cytokine signally into CAR-T cells in order to counter T cell exhaustion, inhibit T cell function 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 for maximize the benefit rates of Allogeneic cell therapy and hopefully our ability to deliver a much needed alternative to patient with multiple myeloma through progressively cell treatment. Lastly, but definitely not least, we’re excited to extend our AlloCAR-T platform into solid tumors. Earlier this year we began dosing patients in our first solid tumor trial ALLO-316 targeting CD70. The diverse trial is enrolling patient with Advanced or Metastatic Renal Cell Carcinoma and is designed to explore various ALLO-316 trial doses. The end point being assess our 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 self therapy specialists to explore allogeneic self therapy in patients with renal cell cancer as a potential meaningful treatment option. Beyond this trial, we’re leveraging internal innovation to expand a utility of our TurboCAR technology platform to address specific biology namely that of tumor like environment in solid tumors. The clinical data presented at the 2021 American Association for Cancer Research annual meeting demonstrates the ability to engineering inducible TurboCAR, which confer cytokine signaling upon buying into PDO1 and PDO2 in the tumor macro environment or when stimulated with an anti-PDO1 antibody. In addition to supplying cytokine signaling this TurboCAR is designed to enhance the therapeutic index of AlloCAR T cell 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 Allogene 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’ve 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 $0.25 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’ll now open the call for your questions.

[Operator Instructions] Our first question is from Salveen 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 looked all the levers together, whole understanding on go-forward pivotal study. How do we think about whether there is 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 Salveen, David Chang here. And let me take that question and also I may ask Rafael to chime in little bit. Certainly, the questions that you’re asking are very important. On data hand we’re very crossedto May 19 when we are planning to have that in 19 day where we will detail all these information. And 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 allogenic in terms of the benefit study come with redosing and others. We also investigate a redosing including the consolidation which is the sort of delay the regiment of how we are investigating different levers. So, 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 most of which is based on a single dose of ALLO-501 cells, we'll get the most informative dataset 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, what is the consolidation, can deepen the response. So, I think there are many different information that it will be included in our CD19 presentation. And 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 presentation. So yes, Salveen, 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 Marc Frahm with Cowen & Company. Your question, please.

Oh yes, thanks for taking my question. David, as you just mentioned that one of the bigger unnoticed rate is that durability of the responses we followed last year and in that that ALLO-501 can generate. So, when we focus on the kind of higher dose of ALLO-647 going forward. I believe there is eight patients a year ago with that dose. Should we thinking about that in the bulk of determining that durability or is there really a large number of patients coming forward. And then, given we think about comparing it to autologous, should we really be looking at, they reported the potency of the cells with reported kind of durable response rates on can 10 to three basis that they tend to be reported on or it's do you think we need to book more holistically, kind of the overall treatment process?

Yes. Thank you for asking both important questions. First of all, in terms of how to better assess the durability. I suggest that we wait till the CD19 day 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 Vascular 2020 presentation as well as additional patients that we have treated since. In ALLO-501, this has been a really great opportunity for us to learn so many different aspects of allogeneic cell therapy that we didn’t know. And with a number of patients that we have treated, we have a lot of confidence about the data set that we have generated. So, and that that's all about a little bit. The second question, 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 Chris Zomato asked a question about questioned about whether mITT is the right way to assess the benefits of CAR T therapy. And since then, we have come long way. And as we advanced to allogeneic CAR T therapy, we feel that there is an opportunity to correct that sort of incorrect use of mITT to assess the clinical benefit to more robust ITT assessment. So, I think this is an important aspect and we will gradually set and try to as it take the field, the value of assessing the treatment benefit based on ITT not just mITT. So, that will be an ongoing process and under doing the CD19 day we will talk about that topic little bit.

Okay, thank you.

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

Hi, hello. Congrats on the progress and then thank you for taking my question. My question's also regarding the consolidation regiment in ALPHA trial. I want to confirm so far all the patients have been treated the way the two doses are at a 120 million cells. And also, do you have a plan to actually increase the dose that with a new information. And are we going to have a data of the T-cell dynamics and the 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 going to declare to the CD19 day. But let me ask Rafael to go through the design and the objective of consolidation and what we expect during the CD19 day. We are learning quite a bit from the consolidation regiment. Rafael?

Yes. So, the concept of consolidation is really to drive deep and in antitumor response that's possible using a second dose that is scheduled as ALLO-501 as you know. So, when we take in rituximab complete response or PR or they only see a day 2018 challengeable to receive this second dose. And you're right, we give a 120 million sales on Day zero and then again on Day 30 or so after the scan is done, we give another 120 million cells. And we're providing this second dose with our chemotherapy and we will sort of enumerate the number of patient that we've been able to do this by follicular and if starts the lymphoma doing the CD19 day and give you some details as to how that is performing. With the caveat that the follow-up is relatively short. I'm just going to emphasize that the reason why we're doing this is if you take advantage of the versatility of allogenic cell therapy and to see whether that 60+% of patients that done benefit in the autonomous setting. We can reduce that number using allogenic therapy and of course in terms of biomarkers we will have the initial be sponsored but we will obviously have expansion trafficking in and obviously drill the season some of the biomarkers. And I will just finish by saying that we do link other patients on the consolidation with the second dose but only with six or seven provided that they need certain hematologic parameters prior to dosing. So, you will definitely see this status at on May 19th.

Thank you, very much.

And Kelly, I would also add that from our perspective. In any Phase 1 study especially with consolidation, the Phase key consolidation portion is important and as well as the early REIT. And early retail will be pretty quick if there is anybody who only achieved partial or stable disease the first cell therapy. Can they get to the complete responses with the second cell infusions? So, there are things that we can figure out pretty quickly and we will present a number of patients as well as what we are seeing with the consolidation regiment.

Very informative, thank you David.

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

Hi, guys. I actually had one of the BCMA program. And perhaps if you could comment on how you're tracking in the universal study towards potentially identifying the recommended Phase 2 dose and protocol and also if you could comment on how the consolidation treatment concept has been incorporated into that study. Thanks, so much.

And 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 what's called different approaches including the combination as well as advancing the next generation. In terms of 715, we're obviously very excited about getting the RMAT designation based on the data that we have presented at ASH last year. And in terms of the questions, I'm going to ask about Paul who really has spent a lot of time on the BCMA to answer ask Rafael who really has spent a lot of time on the BCMA program to answer the questions. Rafael?

Sure. So, my goal would continue to those patients in the 715 program. We now obviously we're producing more than one lot and we're using different doses of six or seven and the T-cell doses. And so, that has continued, it's a very vibrant program and investigators surely will like it because they don’t have to wait, they don’t have to bridge. We as David just mentioned, give us updated data from March to submit to our mat. And we're excited that the agency give that potential benefit of this therapy. And in parallel, we are executing on [indiscernible] that and we are very excited to get started with 605. So, all of this is currently going on and in parallel. And the last point that you rightfully made is the consolidation that is an amendment that we've made to that consolidation in the 715. And we expect to be enrolling on that RM also very quickly. And so, it's a pretty comprehensive program that goes from the CAR by itself to CAR as some add to when neuro-gas is that 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 have a given guidance that we will present updated data by Q4. And then, as with rest of the data with neuro and the 605 accumulate, we will present it but that may take longer in May going to 2022. So, hopefully this gives you a trend that we are fully committed to this program. And it's done and we can sort of appreciate the breadth of it.

Thank you.

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

Hi, guys. Congrats on all the progress. Thank you for taking my question. Question is also regarding the universal program. 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 neuro-gas is that if you're also planning on looking at different dose levels, as low as potentially different dose schedules? I'm just curious if we might explore perhaps giving another dose of neuro-gas that maybe for example in patients that undergo consolidation. Just curious about it, thanks.

Rafael?

Yes. I mean we haven’t disclosed doses that we're using as on neuro-gas is that there's been over a 100 patients treated with our product and this might -- interim studies, the development indication for neuro-gas is that by it's been worked. So, there's a fairly good understanding of it the KPd 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. We all I can say is that we're obviously using dose with we believe are active and that there are still adjustments based on usual parameters such as safety and so on. But beyond that, we think that we have covered the timing that's important to cover for BCMA expression to be as high as possible.

Great, thank you.

Our next question comes from Cory Kasimov with J.P. Morgan. Your question, please.

Hey, good afternoon, guys. Thanks for taking the question. I wanted to ask on your solid tumor program ALLO-316. So, I know that you're just getting off the ground. But as we think ahead to future updates and data redacts 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 uncharted 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 or is tweaking the approach. Thanks a lot.

Hi, Cory that's a great question. And for past 2.5 years, we have focused so much on the hematologic cancer but 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 one-time treatment or few times of cell therapy, potential benefit could really change the trajectory as I've said in the prepared statement of the CAR T therapy or together. The ALLO-316, that's our CD70 directed CAR T program. We prioritize this program based on one thing which is its question of that target which we feel is sufficient safety margin because the 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 trials. And then, ultimately we'll like to see whether this works either alone or in combination with the I-O regimen in solid tumors. But before getting to the tumor reduction and others, I think there are many important questions that we need to address. One of which is how do CAR T-cells expand in patients with solid tumor. And we continually ask this question without ever having to answer the question of our whether engineered our cell therapy. How effectibly they penetrate into the tumor. And whether once they get there they elicit the kind of pharmacodynamics response that one would expect to see. So, they are layers of questions that we will be asking and frankly this is where the translational research team that we built at Allogene will really play a big role in deciphering what happens with the CAR T therapy solid tumors. So, we are very excited about advancing this. And 316, while we are initially targeting renal cell, this is a target that can potentially have utility in many different indications, the solid tumor indications as well as hem malignancies. So, stay tuned and we just started study and hopefully buy early next year. We will be able to update you as well as rest of the field about how our CAT T program is doing inside the tumor. And correct me as going forward, we will be putting more emphasis on solid tumors. I think there is such great opportunity.

Great. Thanks David, very helpful.

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

Hello, thanks very much. Congrats on the progress here. Maybe you want to circle back on Marc's question earlier. I think the last time I checked Zoom or want to see our six months was 33% on an ITT base and 36% on a modified intent-to-treat population. I know the right benchmark that we should have in the back of our mind is we'll see this data. And maybe it will lead you 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 the date on efficacy for all the benefits about Allogene. Maybe for those patients who are autonomous this is simply not an option. Any color there will be great. Thanks, so much.

Luca, I have to say we are asking the same questions and we are actually are not beginning to ask the physicians about these question. Let me ask, Eric, in a too more to put more color to the response to your question. Eric?

Yes, thanks Luca. I mean, certainly appreciate the question and your interest in our views here. I, I honestly think that our May 19 -- CD19 Forum is answer that question in the context of the actual data and, and how we size things up relative to the autologous products. So you will have a lot more to say. And then I do think your ITT and mITT analyses and numbers are the right ballpark. So we see things, pretty, pretty consistently. But I think in terms of laying out the strategy and where we're heading in this field, and in particularly 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 look, I would say one other thing, which is, one of the things that we are trying to achieve with allogeneic cell therapy is trying to treat every eligible patient. Which is something that autologous CAR T therapy has not been able to do. And as you treat every eligible patient, I mean, certainly, this is really moving the, part to the ITT analyses rather than simply compromising the efficacy analysis using the modified intent to treat.

Got it. Thanks so much for super helpful.

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

Hey, thanks for taking my question. I certainly appreciated Rafael's earlier comment that you'll be breaking down response analysis in the ALPHA study by too much 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, Rafael, this is something that, I'm going to refer to ask Rafael to respond. One thing I would say is, we're not going to go too much into specifics about the patient population, but we can give you a general sense of what's going on between these two studies.

Yes, I mean, I would simply say that the, we will have a sizable population of both histology. So unlike at ASCO, 2020, we, 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, you would should expect to see it analyzed both ways, as you know, the 501 study and allows entry of both histologies whereas 501A, it's only large prefer the former, because that's the product that we intend to commercialize. So, we obviously when we get patients, we follow algorithms to try to deciding which study to put them on. But in terms of numbers, I think you not sure we'll see on May 19, 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 ALLO-501 company event on the day that ASCO abstract are released. I think this is clearly something that that we're all looking forward to. But this is also, I guess, just a bit different from how you held these types of events in the past. Or I think these events were held more in line with the actual presentation at the Medical meeting. So I guess just curious what why hold this events or early before the ASCO meeting?

Ben, thanks for that question. I mean, obviously, times are quite different, with virtual meetings being the norm and we're learning, as the sort of prepare for each of the meeting. So, 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.

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

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

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

Hi, thank you for taking the questions, and congratulations on all the progress. I want to ask a question, actually, on the TurboCAR program, maybe hasn't been discussed as much, but you are moving into clinical studies, which is exciting was 605. So the question is, we have not really a one for one comparison, but we do have some idea about utilization of the CAR-T and the CD19 space with PDL1 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 the PDL1, in the setting of at least ALLO CD19 CAR-T has been acceptable. But, there have been some events, although you can't really figure out what whether it was the auto CAR or the Tesla was not consumer. So, just wanted to get your thoughts in terms of how you think about the safety component of that design and what your team specifically considered in that design of the construction.

Now, again, thanks for asking all this important question. I mean, in terms of safety, and in terms of seeing what happens with Turbo. I mean, every time when you are doing something that has been done, I mean, there is a lot of unknowns, and we are doing this in a very carefully orchestrated manner. I mean, the first program the ALLO-605. It is what we would consider, as 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, preclinical results have shown that these cells are much less prone to becoming exhausted. And also in 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 CAR-T therapy setting. At AACR, we also presented a newer version that we are sort of in the process of designing, and this is where, we are trying to leverage the, the science and the technology that is behind TurboCAR to potentially use the negative signals, such as PDL1, or even TGF beta negative signaling and turn that into a positive signal to the cell. So in effect, it provides two ways to make the CAR-T cells work well, in cell tumor one, it provides the cytokine signaling, and two, it has a potential to neutral neutralize the negative signals in the tumor microenvironment. So, this is a work that the team that Barbra Sasu, our CSO has been really leading. And we are sort of beginning and 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 Randy 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 ALLLO-647 is this primarily concerning patient selection or, or why? Why is that a focus as part of that poster presentation and at the risk of the answer being Let's wait till May 19. If I could follow that with a totally separate question, regarding consolidation, have you have you thought about maintenance therapy, especially given that the second dose of constant consolidation doesn't have chemo? Any thoughts regarding maintenance therapy going forward?

Well, I think I should hire you or to be part of a research and development team. You're asking all the right questions, Rafale? I mean, we've been talking about this constantly, some of them that are led to, take this question.

Yes, Rene. This is they're both really good questions. I mean, with regards to 647, it's actually really interesting, I think data said that, we've been able to accumulate with all these patients. So, first of all, we look at the ability of 647 to CAR-T cell depletion, and this receptor C62 [Ph] is not supposed to be on hematopoietic precursors other than, T cell precursors. So, we know that the deeper and the longer the duration of the T cell depletion, the lower the ability of the patient to actually be able to reject ourselves, 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, we are able to actually fine tune these cells. So, this correlation also is made with expansion of the cells. So, this is really important because C52 depletion is kind of the cornerstone of our ability to be able to use allogeneic cell therapy and prevent and prevent rejection. So, the next biomarker we look at is do the cells actually expand and do they persist. So, we go from those two 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, we are doing. Obviously, we've been doing this with single cells, and we are now doing it into consideration arena that we we've 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 the sort of the first forays of consolidation, and we will see what that shows us. And then, we'll eventually make a decision in terms of what we believe is the best doses get and scheduled to go to phase 2.

I would also add. I mean, roughly had made a comment in the consolidation portion, we only lymphodeplete with ALLO-647 without using chemotherapy. This is something very unique. And, that kind of decision is based on the PK/PD analysis of what we have seen so far. And, the question around what are we moving towards patient selection? I think that's just a little bit too early. I mean, I don't think, that's really the goal of this kind of analysis. I mean, the goal of this analysis in 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 Raju Prasad with William Blair, your question please.

Thanks for the question. And congrats on the progress. I had a quick question on the RMAT Designation for 715. Does that income pass the Nirogacestat arm and how are you going to approach or you the honor designation in kind of advancing that arm of the trial? And then just kind of on a regulatory as a kind of part B question. How should we think about maybe applying for designation for our ALLO-501A, are you waiting for maybe a consolidation therapy and maybe moving into pivotal before applying for that? Thanks.

Rafael, do you want to take that question?

Sure. So I think the RMAT Designation for 715, encompass primarily the data that was presented at ASH with some updates. And, obviously, we were delighted to see that the agency recognized the value of the product. And particularly, the doses that the higher doses were we so significant efficacy, including the GPR, 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 our sponsor in terms of requests and so on. But they were satisfied that this was a product that merited, this designation. And we think we intend to take advantage of this designation, obviously, as we move forward BCMA development. With regards to 501 A we are, we started up that program later, as you know, we have more data we 501, but 501 is not the product that we intend to develop. So therefore, we're not seeking RMAT Designation or other designations with 501. We will kick it with 501A, 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 on the data, and then going, but we will be seeking designation as well. And whether we do it before the phase 2 or now, that's a decision that we need to make based on the data that we see. But, I'm always thinking that the sooner that we do this, obviously, the better. But we'll have to make sure that the data is warranted. And that will take a little bit of time for the data to mature.

Great, thank you.

Thank you. Our next question comes from Asthika Goonewardene with Truist Securities. Please go ahead.

Hi guys, thanks for taking my question. So just want to get a quick sense, check your data to suggest that the upfront response may be a key driver of durability and log sell. So just want to get your thoughts as to where you think there's data in the public domain, that also suggests that this is often the case in follicular lymphoma, or is persistence, more is 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 deck. Thanks so much, guys.

In terms of a deep response, I mean, I think that's, based on, basic principle of, the cancer treatment, more cancer cells that you kill you more close to potentially eradicating. So the field really has moved from, the concept of just controlling progression naïve in the maintenance to a more upfront, and whether, the behavior of large B cell lymphoma and follicular lymphoma is going to turn out to be the same or somewhat different. I think, we need to wait a little more for the follicular lymphoma data set to mature, because the study that was done by Kite, that data, time difference is about three years. So I think, time will tell, but, as an oncologist, I do have, this conviction that the more tumor cells that you kill, the more likely that you will have a durable response. MRD response Rafael, do you want to comment on that?

Yes, we see been following MRD response in on an on-going basis on our lymphoma program. As you know it’s not a standard series, obviously, in leukemia, or is myeloma. But we have that data, and we will share, share with the rest of the biomarker what MRD data is today.

Great. Thank you very much.

Thank you. Our last question is from Rob Burns with H.C. Wainwright. Your question please.

Hi, this is Mars [Ph] speaking on behalf of Rob Burns. Thanks for taking my question. In anticipation of data from the universal trial assessing 715. I was wondering if you could provide any indication as to whether the higher dose 715 plus 647 cohort is showing an improvement in response versus your data, the previous conference?

Yes, Rob, you're a little bit -- wasn't coming clearly. But I think the question is whether the 715 at higher dose with a higher lymphodepletion was providing better response. We covered a little bit of that aspect during the ASH presentation last year, and certainly more investigation is on-going. And we will update the data as in the next opportunity that we have, which we project will there 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.

Alright, 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 19, for our Virtual CD19 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.