Allogene Therapeutics Inc (ALLO) 2021 Q1 法說會逐字稿

Good afternoon, ladies and gentlemen. Thank you for standing by, and welcome to Allogene Therapeutics' First Quarter 2021 Conference Call. (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 these calls, we will continue to limit questions to 1 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 patients we have treated so far with our AlloCAR T candidate. From the first patients with relapsed/refractory non-Hodgkin lymphoma treated with ALLO-501 in 2019 to the start of our first solid tumor trial with ALLO-316 earlier this year, we are continuing to define, shape and advance the field of CAR T therapy.

While the initial standards in this field was set by the groundbreaking autologous cell therapy, 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 CAR T 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 AlloCAR T 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 remarks, 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 19.

I think it is also important to note that while we are still treating and collecting data from our ALPHA and ALPHA2 trials to evaluate the full data set prior to next phase, it remains our goal to advance ALLO-501A to a pivotal Phase II 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 CAR T therapy directed at BCMA 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 autologous CAR T manufacturing.

Our recent regenerative medicine advanced therapy for RMAT designation for ALLO-715 was supported by our peripheral concept data. We have continued to execute on our 3-pronged anti-BCMA 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 ALLO-715 in conjunction with SpringWorks' investigational gamma secretase inhibitor, nirogacestat. In addition, we have received IND clearance for ALLO-605, our eagerly awaited first TurboCAR 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 AlloCAR T therapy in myeloma. While our initial candidates target blood cancers and follow in the footsteps of autologous CAR T therapies, we have begun to blaze new trails in solid tumors. We are very excited to be dosing patients in the TRAVERSE trial with ALLO-316, 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 solid tumors and rapidly offer the trajectory of allogeneic CAR T and look forward to executing the study.

From our first day at Allogene just 3 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 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 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 therapy, one that allows us to embrace the inherent benefits supported to an off-the-shelf therapy, the ability to treat every eligible patients, 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 solid 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 AlloCAR T 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 ALLO-501 study together with the 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 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 ALPHA2 trial will report on the Phase I dose escalation portion of this trial. Recall that the ALPHA2 dose escalation phase was designed to quickly confirm that the financing with ALLO-501 translate into ALLO-501A prior to advancing this contract forward into a potential pivotal Phase II 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 ALPHA2 trial. More recently, we have begun treating patients in ALPHA and ALPHA2 under our consolidation dosing protocol. This regimen allows patients who have not progressed after an initial dose of therapy to receive a second schedule administration of CAR T cells with a 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 ALLO-647. As you are aware, ALLO-647 is a key component of our platform, and we believe that it enables a differentiated approach for the patient 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. I 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 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 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. Our most advanced program is ALLO-715, 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 ALLO-715 in combination with nirogacestat, 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 TurboCAR candidate. We are very excited about ALLO-605 as we prepare to launch the Phase I IGNITE trial and learn more about how this proprietary next-generation technology performs in the clinic. As you may recall, TurboCARs 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 risk of allogeneic cell therapy and hopefully our ability to deliver a much needed alternative to patients with multiple myeloma who progressively fail treatments.

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 with ALLO-316 targeting CD70. The TRAVERSE trial is enrolling patients with Advanced or Metastatic Renal Cell Carcinoma and is designed to explore various ALLO-316 trial 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 TurboCAR 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 TurboCARs, which confers cytokine signaling upon binding to PDL1 and PDL2 in the tumor macro environment or when stimulated with an anti-PD1 antibody. In addition to supplying cytokine signaling, these TurboCARs are designed to enhance the therapeutic index of AlloCAR 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, 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 have 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 noncash stock-based compensation expense. General and administrative expenses were $16.4 million for the first quarter of 2021, which includes $8.9 million of noncash stock-based compensation expense. Our net loss for the first quarter of 2021 was $33 million or $0.25 per share, including noncash stock-based compensation expense of $16.8 million.

As mentioned last quarter, we expect to support 5 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 noncash 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.

(Operator Instructions) Our first question is from Salveen Richter with Goldman Sachs.

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 when these trials started?

Good afternoon, Salveen. David Chang here. Let me take that question. And also, I may ask Rafael to chime in a little bit. Certainly, the question that you're asking are very important. On the other hand, we are very close to May 19 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 come with redosing and others, we also investigated redosing, including the consolidation, which is the sort of the later regimen 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 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. So I think there are many different information that it will be included in the -- 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 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 be -- we will provide very informative set of data in our CD19 day.

Our next question comes from Marc Frahm with Cowen and Company.

David, as you just mentioned, one of the big unknowns, right, is the durability of the responses we saw last year and that ALLO-501 can generate. So when you've focused on the kind of higher dose of ALLO-647 going forward. I believe there's 8 patients a year ago with that dose. Could we be thinking about that being the bulk of determining that durability? Or is there really a large number of patients coming forward? And then when we think about comparing it to autologous, should we really be looking at the reported -- 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?

Marc, thank you for asking those important questions. First of all, in terms of how to best 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 ASCO 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 of. And 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 up a little bit. The second question of 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 Amaco] asked a question about -- questions about 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 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 sort of try to educate the field the value of assessing the treatment benefit based on ITT, not just MITT. So that will be a ongoing process. And on the -- during the CD19 day, we will talk about that topic a little bit.

Our next question comes from Kelly Shi with Jefferies.

Congrats on the progress. My question is also regarding the consolidation regimen in ALPHA trial. I want to confirm, so far all the patients have been treated with 2 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 the biomarker studies for redosing cohort at ASCO?

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 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?

Yes. So the concept of consolidation is really to drive a deep antitumor response as possible using a second dose that is schedule of ALLO-501, as you know. So any patient who's 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 0. And then again, on day 30 or so after the scan is done, we gave another 120 million cells. And we are 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 large cell lymphoma during 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 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 that 60%-plus 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 minimal residual disease and some other biomarkers. And I will just finish by saying that we do lymphodeplete patients on the consolidation with the second dose, but only with 647, provided that they need certain hematologic parameters prior to dosing. So you will definitely see the status on May 19.

Hey Kelly, I would also add that from our perspective, in any Phase I study, especially with consolidation, the safety of consolidation portion is important and 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 the first cell therapy, can they get to the complete responses with a second cell infusion. So things that we can figure out pretty quickly, and we will present the number of patients as well as what we are seeing with the consolidation regimen.

Our next question comes from Michael Schmidt with Guggenheim.

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 II dose and protocol? And also, if you could comment on how the consolidation treatment concept has been incorporated into that study?

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 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 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 dose patients in the 715 program. We have -- obviously, we're using more than 1 lot. And we're using different doses of 647 and 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 give the potential benefit of this therapy. And in parallel, we are executing on nirogacestat, 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 (inaudible) nirogacestat, the use of 2 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 given guidance that we will present updated data by Q4. And then as the rest of the data with niro and 605 accumulate, we will present it, but that may take longer and may go into 2022. So hopefully, this gives you a sense that we are fully committed to this program, and it's -- and you can sort of appreciate the breadth of it.

Our next question comes from John Newman with Canaccord.

Congrats on all the progress. 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 nirogacestat, 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 nirogacestat maybe, for example, in patients that undergo consolidation? Just curious there.

Rafael?

Yes. I mean we haven't disclosed the doses that we're using of nirogacestat. There's been over 100 patients treated with that product in the desmoid syndrome, that is the development indication for nirogacestat by SpringWorks. So there's a fairly good understanding of the PK/PD 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 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 the timing that's important to cover for BCMA expression to be as high as possible.

Our next question comes from Cory Kasimov with JPMorgan.

Wanted to ask on your solid tumor program ALLO-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 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 versus tweaking the approach?

Hey Cory, that's a great question. And I know for the 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 onetime treatment or a few times of cell therapy potential benefit could really change the trajectory, as I've said in the prepared statement about -- of the CAR T therapy altogether. ALLO-316, that's our CD70 directed CAR T program. We prioritize this program based on one thing, which is the expression of the target, which we feel gives sufficient safety margin because 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 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 answered the question about what are 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 expect to see.

So there 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 in solid tumor. 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, (inaudible) indications as well as heme malignancies. So stay tuned. And we just study. Hopefully, by early next year, we will be able to update you as well as rest of the field about how our CAR T program is doing in solid tumor. And secondly, as going forward, we will be putting more emphasis on solid tumors. I think there is such great opportunities.

Our next question comes from Luca Issi with RBC Capital.

Congrats on the progress here. Maybe I want to circle back on Marc's question earlier. I think last time I checked ZUMA-1, the CR 6 months was 33% on an ITT basis and 36% on a modified intent to population. 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 it 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 who are autologous it's simply not an option. Any color there would be great.

Luca, I mean, I have to say, we are asking the same questions, and we are actually now beginning to ask the physicians about these questions. But let me ask Eric 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 honestly think that our May 19 CD forum -- 19 forum is to answer that question in the context of the actual data and how we size things up relative to the autologous products. So we'll have a lot more to say then. I do think your ITT and MITT analyses and numbers are the right ballpark. So we see things 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 one of the things that we are trying to achieve with the 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 patients, I mean, certainly, this is really moving the bar to the ITT analysis rather than simply compromising that because their analysis using the modified intent-to-treat.

Our next question comes from Mark Breidenbach with Oppenheimer.

I certainly appreciated Rafael'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 were 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 population, but we can give you a general sense of what's going on between these 2 studies.

Yes. I mean I would simply say that we will have a sizable population of both histologies. So unlike at ASCO 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 we should expect to see it analyzed both ways. As you know, the 501 study allows entry of both histologies, whereas 501A is only large B-cell lymphoma because that's the product that we intent to commercialize.

So 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, as you will see on May 19, we'll be able to show a good representation of both.

Our next question comes from Ben Burnett with Stifel.

You guys are holding the ALLO-501 company event on the day that ASCR 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. Or 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?

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

Ben, 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 virtual this year, not a lot of people realize that the embargo lists 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 advantage of the opportunity to stay out of the rush of the full conference activities and host our event on the 19 so we could dedicate a substantial amount of time to what will get us the full update on the program.

Our next question comes from Dane Leone with Raymond James.

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 with 605. So the question is, we have not really a one-for-one comparison, but we do have some idea about utilization of auto CAR T in the CD19 space with PDL1 via the ZUMA-6 study and some others. I just want to get your thoughts in terms of how your team was designing the program design of CARs, how you thought about safety components. Generally, it seems like the sequencing or actual overlap of use of PDL1 in the setting of at least auto 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 atezolizumab and ZUMA-6. So just want to get your thoughts in terms of how you think about the safety component of design and what your team specifically considered in that design of the construct?

Yes. Yes, Dane, 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 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 3 as part of the activation process and 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 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 science and the technology that is behind TurboCAR to potentially use the negative signals, such as PDL1 or even TGF data, negative signaling and turn that into a positive signal to the cell. So in effect, it provides 2 ways to make the CAR T cells work well in solid tumor. One, it provides the cytokine signaling. And 2, it has a potential to 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. 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.

Our next question comes from Reni Benjamin with JMP Securities.

I guess I'd love to get a little bit more color or an idea of the biomarkers that you are looking at for ALLO-647. Is this primarily concerning patient selection? Or why is that a focus as part of that poster presentation? And at the risk of the answer being wait till May 19, 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, 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 take Reni's question.

Yes. Reni, these are both really good questions. I mean with regards to 647, it's actually really interesting I think data set that 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 C52 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 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 able to actually fine-tune this dose. 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 allogeneic cell therapy 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 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 we are doing. Obviously, we've been doing this with single cells, and we are now doing it in the consolidation arena that 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 dose and schedule to go to phase II.

I would also add, I mean, Rafael 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 whether we are 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, how to best use the 647 for the intended purpose of lymphodepleting safely and appropriately.

Our next question is from Raju Prasad with William Blair.

Congrats on the progress. I had a quick question on the RMAT designation for 715. Does that encompass the nirogacestat arm? And how are you kind of going to approach or use the -- on that designation and 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 ALLO-501A? Are you waiting for maybe the consolidation therapy and maybe moving into pivotal before applying for that?

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 at the doses that -- at the higher doses where we saw significant efficacy and including VGPR 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 the sponsor in terms of requests and so on, but they were satisfied that this was a product that merited this designation.

And we intend to take advantage of this designation obviously as we move forward BCMA development. With regards to 501A, we are -- we started up 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 RMAT designation or other designations with 501. We would seek 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 in the data and then go in, but we will be seeking designation as well. And whether we do it before the phase II or not, 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 warranted, and that will take a little bit of time for the data to mature.

Our next question comes from Asthika Goonewardene with Truist Securities.

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 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 -- 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 day?

In terms of the deep response, I mean, I think that based on basic principle of the cancer treatment, more cancer cells that you kill, you are more close to potentially eradicating. So the field really has moved from the concept of just controlling progression, i.e., maintenance to more upfront. And whether the behavior of large T 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, the data time difference is about 3 years. So I think time will tell. But as an oncologist, I do have this conviction that the more tumor cells that you kill more likely that you will have a durable response. MRD response, Rafael, do you want to comment on that?

Yes. We've seen following MRD response in -- on an ongoing basis on our lymphoma program. As you know, it's not a standard as it is obviously in leukemia or it 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.

Our last question is from Rob Burns with H.C. Wainright.

(inaudible). So in anticipation of the update 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 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.

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 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.