Allogene Therapeutics Inc (ALLO) 2020 Q3 法說會逐字稿

Good morning, ladies and gentlemen, thank you for standing by, and welcome to Allogene Therapeutics' Third Quarter 2020 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 good morning. Before market opened today, Allogene issued a press release that provides a corporate update and financial results for the third quarter ended September 30, 2020. This press release is available on our website at www.allogene.com. Today's call is being webcast on our website and will be available for replay. 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 2020 financial guidance, among other things. These forward-looking statements are based on current information, assumptions and expectations that are subject to change. These statements involve risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements. These and other risks are described in our periodic filings made with the Securities and Exchange Commission, including our Form 10-Q for the quarter ended September 30, 2020. You are cautioned not to place undue reliance on these forward-looking statements, and Allogene disclaims any obligation to update these statements. I'll now turn the call over to Dr. David Chang.

Thank you, Christine, and my thanks to all of you for joining us on our third quarter conference call during a very busy weekend new cycle. Given that this promises to be an eventful morning, we are going to keep today's prepared remarks short and focused on a few key areas. I will start with CD19, specifically our plans with ALLO-501 and ALLO-501A and our path to investigating AlloCAR T therapy in solid tumors. Later in the call, Rafael will speak to the work we are doing to advance our BCMA directed therapies, including our plans to present our initial Phase I data from our first BCMA product candidate, ALLO-715 in an upcoming scientific meeting later this year.

Let's start with our CD19 program in relapsed and refractory non-Hodgkin lymphoma. We believe that peripheral concept data we presented at ASCO provides a strong foundation of support of our efforts to make AlloCAR T therapy a reality. However, one outstanding question for the allogeneic field is durability of response. Durability is critical to the value proposition of any CAR T therapy, and we firmly believe that the answer to durability lies in how we utilize lymphodepletion, optimized cell dose and embrace dosing flexibility that is viable and scalable with an off-the-shelf cell therapy.

We have spoken at length about lymphodepletion and how we are optimizing the dose of ALO-647 our anti-CD52 monoclonal antibody in concert with a standard, fludarabine and cyclophosphamide while flu/cy regimen to create the ideal depth and duration of lymphodepletion to allow robust expansion and persistence of AlloCAR T cells.

In our view, such a controlled immune suppression is necessary to maximize the tumor cell killing while minimizing the risk of cytopenia and opportunistic infection. We continue to believe that this approach of utilizing ALLO-647 as a differentiated component will help us to achieve our goal of providing a meaningful clinical benefit with allogeneic CAR-T therapy. The initial readout from the ALPHA Phase I trial also gave us a glimpse that, what may be one of the more exciting benefits of our potential after-shelf therapy, the ability to redose patients.

In the case study presented at ASCO, one patient dosed with 120 million cells of ALLO-501 following the lymphodepletion with a standard flu/cy and the 39-milligram dose of ALLO-647 achieved a partial response but subsequently progressed in month 2. Shortly after progression, the patient was retreated with 120 million cells of ALLO-501. And this time, with a flu/cy and the 90-milligram dose of ALLO-647, which led to a complete response.

In the autologous setting, CAR T dosing regimens are shaped by the inherent limitations in self supply. Rather than applying autologous thinking to the design of an allogeneic trial, we want to exploit the benefit of allogeneic therapies to better understand the potential for repeat dosing. In particular, we plan to explore the risk-benefit profile of a scheduled repeat dosing, which we will refer to as consolidation therapy in the ALPHA trial. Practically speaking, the consolidation therapy entails treating patients without disease progression after the first AlloCAR T therapy with a second dose of AlloCAR T approximately 5 to 6 weeks later. Our hope is that this back-to-back dosing or consolidation might enable more patients to achieve deeper responses and maintain a durable remission. As enrollment continues in our ALPHA and ALPHA 2 Phase I trials, we expect a rich data set to emerge.

Pending data, our current plan is to initiate a potential pivotal Phase II trial of ALLO-501A in 2021. We look forward to showcasing this holistic view on the CD19 programs progress, including additional data from ALLO-501 ALPHA trial and the dose escalation phase of ALLO-501A, ALPHA2 study in the first half of 2021.

The next update I would like to provide is on ALLO-316, our anti-CD70 AlloCAR T candidate. As we prepare to file our IND in renal cell carcinoma, or RCC, this quarter, our enthusiasm increases for the start of our clinical trial in 2021 and the potential to explore ALLO-316 in solid tumors. We look forward to presenting additional preclinical data this year and believe RCC may be just the beginning of what can be addressed by ALLO-316, given the expression of CD70 in lung cancer, glioblastoma and hematologic malignancies.

We could not be prouder of our teams at Allogene and the progress made not just across our development pipeline, but also the work being done to complete our state of the art manufacturing facility, which we expect will begin producing clinical GMP labs in 2021. Our unwavering focus on bringing AlloCAR T therapy to patients has allowed us to quickly advance multiple AlloCAR T candidates.

In 2021, just our third full year as a company, we expect to have 5 clinical trials underway, including one pivotal trial, our initial endeavor into solid tumors and our first study using our TurboCAR T technology.

I will now turn the call over to Rafael for further updates on our research and development activities, with a specific focus on ALLO-715 and our BCMA program.

Thank you, David. I noticed seeing considerable interest in our forming ALLO-715 presentation in patients with relapsed/refractory and multiple myeloma, and I am excited to provide an update on our BCMA platform more broadly. Our prior Phase I data presentation of ALLO-501 at ASCO was an important step towards validating our platform, as it addressed key questions, including the successful manufacture of an allogeneic CAR T therapy, the ability to administer therapy without causing clinically relevant graft-versus-host disease, the use of ALLO-647 to enable deep and selective lymphodepletion required for cell expansion and the finding that allogeneic cell therapy can generate meaningful antitumor activity.

We hope the initial look at our UNIVERSAL Phase I dose escalation trial might reconfirm these foundational observations in a different disease setting, thereby positioning us to move on to the next steps in this study namely optimizing cell dose, lymphodepletion and potential repeat administration of ALLO-715. Initial data set from UNIVERSAL may also allow us to apply insights across our BCMA platform. Central to our efforts, it's a recognition that an allogeneic CAR T option may be critical for patients with multiple myeloma, many of whom are not in a position to wait for the availability of an autologous option.

Investigators have told us that there are significant wait times associated with the delivery of autologous cells and that the use of bridging chemotherapy during this treatment interval is quite common. As we execute on our trials, we aim to exploit the fundamental advantages of allogeneic CAR T therapy with regards to its on-demand availability. For example, in our UNIVERSAL trial, rapid treatment time lines obviate the need for bridging therapy. While the initial Phase I data we will present later this quarter will be focused on the initial dose escalation portion of the trial, our ultimate goal is to be comparable to the results seen in autologous anti-BCMA CAR T therapies in later-stage trials.

The UNIVERSAL study of ALLO-715 was initially designed to explore optimal dosing of all components of the lymphodepletion regimen including ALLO-647, fludarabine and cyclophosphamide with patients receiving ALLO-715 at 1 of 3 doses: 40 million, 160 million and 320 million cells in a 3 plus 3 dose escalation design. As we noted last quarter, we have completed the initial dose escalation portion of the UNIVERSAL trial using 39 milligrams of ALLO-647 and began enrolling other lymphodepletion cohorts, one of which omitted fludarabine and one in which we increased the dose of ALLO-647.

The endpoints being assessed are safety, tolerability, depth and duration of lymphodepletion, cell expansion and signs of antitumor activity. The multiple variables in the trial design and our ability to fully optimize each component of the therapy will be critical to creating the best product profile for the myeloma setting.

Much like the abstract for ALLO-501 at ASCO, the first look at ALLO-715 data will occur prior to formal presentation and will include high level data on the first 15 evaluable patients treated with escalating doses of ALLO-715 and 39 milligrams of ALLO-647. Selectivity will be based primarily on day 28 tumor assessment. We expect to present detailed results at a virtual medical meeting later this year. That presentation will include data on approximately 20 patients across the initial 3 ALLO-715 cell dose cohorts, a lower dose, 39 milligrams of ALLO-647, as well as a few patients treated with higher doses of ALLO-647.

While we may explore the consolidated cell dosing strategy as discussed in the ALPHA trial, we have not yet predosed patients in the ongoing UNIVERSAL trial. As we keep an eye towards what might be possible in the future with AlloCAR T therapy in a disease, such as multiple myeloma, we are progressing our BCMA program to include the study of ALLO-715 in combination with the gamma secretase inhibitor. An IND to support the combination of ALLO-715 and nirogacestat from our partners at SpringWorks Therapeutics is on track to be filed this year, and we are excited to initiate the trial next year. We also look forward to evaluating our TurboCAR technology in the setting of myeloma. We continue to believe that the innovation behind TurboCARs could be a breakthrough, as this technology has the potential to overcome T cell exhaustion and expand AlloCAR T cell viability and efficacy while reducing CAR T cell dose requirements.

These properties may enable CAR T success in harder-to-treat hematologic malignancies and solid tumors and prove to be an important opportunity to raise the bar in multiple myeloma treatment. We look forward to soon sharing additional preclinical data of ALLO-605, our first TurboCAR clinical candidate and next-generation AlloCAR T therapy in multiple myeloma and have accelerated work necessary to now submit an IND for ALLO-605 in the first half of next year. We remain enthusiastic about our AlloCAR T platform and what it potentially mean for patients. We look forward to continuing to provide updates, scientific congresses to share our progress in the near-term for ALLO-715, in the first half of next year for ALLO-501 and ALLO-501A. I'd like to now turn the call over to Eric to review financials.

Thank you, Rafael, and good morning. We appreciate that you are likely to be very busy this morning. So let me be brief in my remarks. As noted in our SEC filings and third quarter press release issued earlier today, our financial position remains strong with cash, cash equivalents and investments totaling $1.0 billion as of September 30, 2020. In the third quarter, our research and development expenses were $51.4 million, which includes $8.8 million of noncash stock-based compensation expense. General and administrative expenses were $16.6 million for the third quarter of 2020, which includes $9 million of noncash stock-based compensation expense. Our net loss for the third quarter of 2020 was $66.2 million or $0.52 per share, including noncash stock-based compensation expense of $17.8 million. A few quick corporate updates include that we are nearing completion of construction for our self manufacturing facility in Newark, California, as mentioned by David. And as we prepare for a pivotal trial and beyond, we see GMP manufacturing from this facility expected in 2021.

On the business development front, we were very pleased to expand our relationship with the University of Texas MD Anderson Cancer Center with a strategic 5-year collaboration aimed at accelerating the development of a broad AlloCAR T portfolio across hematologic and solid tumors.

Under the agreement, we plan to collaborate with MD Anderson on the design and conduct of preclinical and clinical studies. Dr. Christopher Flowers, Interim Division Head of Cancer Medicine and Chair of lymphoma and myeloma at MD Anderson and a key opinion leader in the field of cell therapy will play a key role as we advance this collaboration.

Lastly, 2 Servier sponsored trials with UCART19 and ALL have been completed or nearing completion with no additional patients planned for enrollment.

We in Servier are now reviewing the development strategy for ALL, which may include the possibility of consolidating our programs around a single manufactured cell product, ALLO-501A. As we near the end of the year, we continue to guide to full year 2020 net losses of between $260 million and $280 million, which includes estimated noncash stock-based compensation expense of $70 million to $75 million and excludes any impact from potential business development activities. With that, we will now open the call to your questions.

(Operator Instructions) Our first question comes from Marc Frahm with Cowen.

Maybe with the BCMA abstract having come out this morning, there's a patient death reported in there that was associated with the conditioning regimen. Can you -- is there any further details you can provide us to, was the attribution kind of given to within the various agents of the preconditioning and what makes you confident that whether ALLO-647 is contributing or not?

Mark, this is Dave Chang. Let me take your question. I think we were a little bit surprised about the abstract coming out today because the scheduled release of abstract was supposed to be tomorrow. And I think you're pointing out around the fact that we report one case of Grade 5 event, which occurred in patients who lymphodepleted with cyclophosphamide and ALLO-647.

So if anything, this is a patient who received lesser lymphodepletion than other patients in studies in the trial. The patient had a pretty rapidly progressing disease. And the initial symptoms of what was considered was -- as pneumonia was diagnosed on the day of solid fusion, and it remains somewhat refractory to treatment.

And as the patient's course deteriorated, the family simply wanted a comfort care, which was pursued and the patient expired on day 8. It is an unfortunate incident. But I should remind you that both in the autologous cell therapy, both serious adverse events and that has been observed. And we have to realize that we are dealing with very sick patient population. I mean, this particular patient unlike most patients with multiple myeloma had remained refractory to all previous lines of therapy and was progressing pretty rapidly.

So as a physician having dealt with patients who had a rapidly progress, this is a very difficult situation. And in this case, unfortunately, the patient died from Grade 5 event.

And next question comes from Salveen Richter with Goldman Sachs.

Could you talk about the various lymphodepletion regimens you're looking at in the multiple myeloma study and including or removing flu/cy and how this might help with regard to the safety profile? And then secondly, just given the ASH abstract today, how do you view the dose response seen to date and just the overall profile in the context of the autologous data at this point?

Okay, Salveen, thanks for the question. And I'm going to -- I'll refer the question to Rafael Amado. Rafael?

Yes. Thanks for the question. So we designed a trial to test flu/cy, ALLO-647 and also to sequentially be able to remove cyclophosphamide -- first fludarabine and then cyclophosphamide and then subsequently explore higher doses of ALLO-647. And we're really in the midst of doing this. I mean, we are -- we still have a little bit of way to go. We did drop fludarabine, such as indicates it was just described and we observed slightly lower outcomes, and we decided to go back to FCA.

We completed FCA at 39 milligrams and we continue to explore other doses of ALLO-647. So I don't want to get ahead of the presentation, but most likely our conditioning will include all 3 agents at this point.

Our next question comes from Biren Amin with Jefferies.

Just on the ASH abstracts, I think you talked a little bit about the Grade 5 event, but you also had 3 other Grade 3 or greater infections. Can you just talk about that relative to the higher dose of ALLO-647, whether you foresee a potential increased risk of Grade 3 or greater infections with the higher 90-milligram dose?

So Biren, let me take that question. In terms of serious adverse events or infections, let me just emphasize, I mean these are not an infrequent events in chimeric antigen receptor cell therapy. So yes, I know that there is a sort of tightening in attention given to our trials about opportunistic infection. But at this point, the degree of infection that we are seeing in my opinion, and I think many clinicians would agree, especially in the refractory multiple myeloma, it's not really raising -- obviously, it's a Phase I study, we're looking at the safety very carefully, but it's not raising heightening concerns. And frankly, at this point, we are continuing on with the clinical study. And the study conduct has never been changed.

And as Rafael had remarked during the prepared statements, we are exploring higher lymphodepletion conditioning using higher dose ALLO-647. And the questions about how that looks like, I mean those details, you will have to wait for the ASH presentation.

Our next question comes from Tyler Van Buren with Piper Sandler.

In the abstract, it mentions, 4 out of 5 responders were still in response at the time of data cutoff. So I wanted to ask a question related to that. Can you provide us maybe details on when that one responder progressed, at what time point? And then also where the 4 responders are in terms of duration of response?

Okay. Yes. Yes. Tyler, I think some of these questions are better to be waited for the actual data presentation at ASH. But let me ask Rafael to provide some additional comment.

Yes. I mean it's the durability of response of that particular patient and you have to understand it was a relatively short follow-up. So it was a matter of a few months and then the other patients I think we'll have to see when we present the totality of the data.

Our next question comes from John Newman with Canaccord.

Different question on ALLO-501. And the question is, David, so we're all anxiously waiting for durability results in the first half, but I'm just curious, from a manufacturing standpoint, if the durability for this product turns out to be better than we expect, do you feel confident that when the product is approved, you'll be able to meet potentially increased demand?

Yes, John, great question. That question -- we used to get a lot of those questions and it sort of died out. But our manufacturing process, I mean, the technical operations team have been continuously improving the yield, and improvement in yield comes from many different ways because at the end, what we give to the patients car CAR positive cells.

So the transduction efficiency, cell viability, all these things lead to what we can consider as a dose that we can use from a single manufacturing one. And all along, we've been saying that even from the beginning that each manufacturing one can potentially treat up to about 100 patients. And I think we feel pretty comfortable maintaining that statement. So the yield is quite good. If anything, the manufacturing process is improved while we are continuing the study. And we feel very confident that as we move forward, the manufacturing of the product will not be a major issue for us.

Our next question comes from Cory Kasimov with JPMorgan.

I wanted to ask about the potential for redosing 501 or any of your AlloCARs for that matter. I'm just wondering, is there any read-through from the ALPHA study on that front in terms of durability or possibly you need to increase durability that's driving this desire, this approach, or is it just another way to potentially differentiate the product in your platform?

Yes, Cory, great question. I would say that it's really the potential of redosing that we really want to explore. We at ASCO talked about a single patient, with the first treatment, patients only achieved a partial response, and with the second treatment with essentially same cell dose but with somewhat enhanced lymphodepletion and a patient achieved a complete remission.

That's a pretty unusual situation where the initial response was improved with retreatment. So when we think about it, I think that really creates an opportunity in the context of what we know about CAR T [drug] therapy in non-Hodgkin's lymphoma. The response rate is high, but some of the responses are not complete responses, partial responses. And partial responses tend to progress relatively quickly. So that's the setting.

And here, what we are trying to achieve is, let's treat the patient with a first cell therapy. And at month 1, which is when we do the first tumor assessment, patients who have evidence of disease progression, unfortunately, they will come off the study. However, anybody who has an evidence of response or a stable disease, we are planning to retreat or essentially consolidate the tumor response with a second cell infusion.

And we think -- we believe that we can do that within first 5 to 6 weeks of treatment, which essentially, from our perspective, would complete the planned dosing of the 501 in those patients. So what we're really hoping is that with the second dose, we'll push more patients to complete remission. And if you look at all of the existing data, patients with complete remission tend to have a more durable response. So that is sort of what we are looking for. And obviously, the durability will take a little bit longer for us to get a sense about how the durability will last.

And frankly, we're still following the durability of patients who responded after a single infusion, which some of them will be presented at the ASCO presentation. And those we plan to update the data in the first half of 2021.

Our next question comes from Michael Schmidt with Guggenheim.

I just wanted to follow-up on ALLO-715 and the infection rate. I mean, I guess, David, you mentioned already, but how does the Grade 3 or higher infection rate compared to those that seen with autologous CAR T programs? And is the risk maybe higher or different you think in diseases like multiple myeloma as opposed to non-Hodgkin lymphoma?

Yes. The underlying medical conditions does make a lot of difference. Certainly -- patients with multiple myeloma with essentially refractory disease, they are much higher with infection. In terms of the rates, I don't have the details about what has been reported in the positive setting. Maybe -- Rafael, do you know that answer?

No, but there's -- it's a fair number of infections as well, but we can get the exact number and send it later. But I mean multiple myeloma patients are very prone to infections. They are hypogammaglobulinemia and they develop infections spontaneously as well. So it's -- they are fairly common, especially in late-stage disease, like the ones that we [talked].

Our next question comes from Mark Breidenbach with Oppenheimer.

David, I'm wondering if you can tell us if any of the responders in UNIVERSAL achieved MRD-negative status?

Mark, sorry. Can you repeat the question?

Sure. Sure. I'm just wondering if any of the responses that you saw in the UNIVERSAL trial dose escalating study were MRD-negative.

Yes. Great question. I know that we've been fielding a lot of questions about the Grade 5 events and infection, but I'm glad that you are talking about the efficacy side of the equation. Certainly, we are seeing ALLO-715 as an active compound. I mean there is a cell dose response relationship, but we are seeing very good evidence of response as we go to the higher cell doses.

And to the question, what we are seeing at the higher cell dose, the response [varies relatively quickly] within first 28 days. And the response tends to be pretty deep to begin with in a stringent complete remission and the very good partial responses or what we saw at cell dose of 320 million. And both of those patients had a MRD negativity by the local MRD testing.

Our next question comes from Dane Leone with Raymond James.

And it's just kind of classic 2020 at this point for the ASH abstracts to randomly come out this morning. So I'll ask this, since you've had a lot of questions on the abstract data itself, from a drug development strategy in myeloma, how are you thinking about patient disposition? And what I mean by that is you have blend rep, which is now being used as a late-line BCMA-targeted agent. You do have the auto CAR T programs, [IDO cell and the J&J] program that will probably be approved sometime within the near future, and from speaking with the multiple myeloma community and the docs treating these patients in the later lines, the consistent response has been blend rep does seem like a good option for these patients. You might think about but probably reach for (inaudible). Auto CAR T in the late-line is great, if you can do it for the patients and they don't have rapid progression. So where are you thinking about what type of patients you really want to start focusing on as you get into the later stages of ALLO-715 program? And how you would think about this strong product fitting into the continuum of treatment as it's evolving?

So Leone -- I'm sorry, Dane. I mean, that's a great question. I mean, I think some of the questions that you're asking also relates to the question that we did not respond to Salveen. And if our initial question about comparison of our data to what has been reported for the autologous cell therapy. One thing that I will say is in multiple myeloma, as we all know, there is a lot of treatment options that are available. And frankly, patients remain on treatment for a long period of time because that's how some of the proteasome inhibitors as well as IMiDs has been developed. One thing that we constantly hear from the physicians are that, yes, there are certain options, but none of these treatments really provide what will be a pure and also all these patients will eventually progress.

So from the existing therapy perspective, I mean, there are 3 major categories of drugs that are being used: proteosome inhibitor, IMiDs, IMiD modulating drugs, such as (inaudible) and then the third one, CD38 monoclonal antibody therapy.

Essentially, the patient population that we are targeting are the ones who have already come through those existing therapy. And this is where now BCMA-targeted therapy, whether it's the chimeric antigen receptor or ADC, it really fits in. I think the good thing about all the efforts that different companies are making is that at the end, there will be more treatment options that physicians and patients can use. And to some extent, it will depend on the physicians comfort level as well as preference.

However, we definitely see a situation where different BCMA-targeted therapy can potentially be sequenced. The data, it's still premature in many ways, but I think we are beginning to see some sense, maybe there are some differences in the response rate. However, so far, the progression-free survival, they all seem to give a similar number. I think that's the current -- early read of the data, which obviously, we will have to know more. So that's the setting. And what we are coming with our BCMA-targeted programs in 715, I mean, as an off-the-shelf therapy that can potentially give a deep response that's durable, I think we can position our product well in this space, once we complete the pivotal study.

I hope this is sort of answering your question but the nature of your question until all the dust settles, I mean, it's somewhat speculative at this point. But we have a clear position on how we want to put our product in this space.

Our next question comes from Ren Benjamin with JMP Securities.

Just with ALLO-501A, can you just remind us the doses that are being evaluated, about how many patients' worth of data we might see in the dose escalation phase of the study. I'm just wondering if we have to kind of go back to the drawing board, or did we hone in on particular doses? And just related to that, I guess, 501 is supposed to be the test kitchen, I just wanted to know if there's anything new being cooked up that would be of interest.

Yes. We are really taking advantage of hitting 2 studies in 501, which is really the proof-of-concept construct candidate that we have generated data, and we already sort some data. And then there's a 501A, which we are positioning for the pivotal study.

So to the first part of the question, we're really following what we have done in the 501 -- with the 501A in a very accelerated way. I mean, in many ways, we are just testing to make sure that there are any surprises unexpected there will be, of course, we have no reason to think that these 2 will behave in any different ways. But I think it's very important to confirm that in the clinical setting.

So we are sort of following what was done in the 501 in a very accelerated way. While that's going on, 501, it really gives us an opportunity to test things in many different ways. And obviously, the main thing that we are going after, as we explore different things, is trying to increase the adaptive response, trying to improve the complete remission rate, and as we talked about, consolidation is one strategy, while we wait for the durability of the response from patients who have responded.

So that's more or less the underlying theme of how we are positioning these 2 studies. And in terms of the details of the data, number of patients and all those things, that will sort of provide additional color to it, when we present the data in the first half of 2021.

Our next question comes from Raju Prasad with William Blair.

Just wanted a little bit of color on the 715 and nirogacestat trial, particularly in how the trial design kind of will build on kind of learnings from the UNIVERSAL with regards to cell dose and lymphodepletion regimen, is -- will you have to kind of restart a 3 for 3 design trial or will you be able to kind of take some of the learnings from the UNIVERSAL trial and just add it to -- and add an arm with the GSI?

Okay. Rafael, do you want to take on the question?

Yes, sure. I mean, we will -- sorry. I will just very briefly tell you what we plan to do. The nirogacestat dose, we will leave constant. And we may start -- we're not going to start with lower doses as we started in 715. We are planning to start with [new] doses and then dose escalate. So most likely 120, and then depending on what we've seen with the higher doses of ALLO-647, then we'll decide which 647 dose we will use, and we're going to use FCA. So it will be -- there will be some dose finding, but it will be pretty expedited.

And our next question comes from Asthika Goonewardene from Truist Securities.

David, I just wanted to touch back on the previous slide that you had on the MRD-negative status on 715. Those 2 patients, were you able to get any color on if they are MRD-negative 5 or MRD-negative 6? And then just maybe bigger picture here thinking about the consolidation strategy. Could you maybe tell us about how you're thinking about dosing cy/flu in that consolidation approach? And if you -- and what are the things you're thinking about in terms of managing toxicities and kind of develop your protocol around that?

Yes. Great questions. Let me take on the consolidation, and I'm going to ask Rafael about the MRD data set coming from the 715 study. I mean, I'd say that we are very encouraged with the kind of MRD-negative you're seeing in the responders where the responses are happening very early in the BCMA trial. That -- on the question about the consolidation, I mean, we are -- we will detail in terms of how we lymphodeplete in the first time and the second line. But I would say that because of the ALLO-647, we do have a lot of flexibility in terms of how we can maintain the lymphodepletion through both first and the second treatment.

So without going too much into the clinical trial details, let me just end by saying that the question is great. Not being able to -- not needing to use chemotherapy all the time for lymphodepletion which is really another advantage that comes with ALLO-647 that we are trying to incorporate in the design of the consolidation.

So sorry that I'm not providing the exact details, but some of these competitive information. So I'm much sure to defer until the trial opens.

Yes. With regard to -- with regard to MRD.

Rafael taking the MRD?

Yes, very briefly. This were done by the site. We have a central lab that will do MRD stringent level, 10 to minus 6, and we will supply whatever data we have on that from the central lab, but this was done 10 to minus 5 on local lab at the hospital.

And our next question comes from Luca Issi with RBC Capital.

Two quick questions here. The first is, it is my understanding that state therapeutic actually will show data for their NK CD19 CAR at ASH. What are your expectations around that data? And then maybe a higher level, what are some of the potential advantages and disadvantages of using T cells versus NK cells here? And then the second question, obviously, on the abstract, I think -- just I want to confirm it, no patients received the high dose of ALLO-647 and 90-milligrams in the abstract, are we going to see that data at ASH or will it be in 2021?

So in terms of the first question, which is really NK versus the T cells, I mean the biology as well as existing clinical data are very clear. I mean, all the cell therapy data, where strong responses have been seen whether -- so you're talking about pills and chimeric antigen receptor. And that's all coming from the T cell-based therapy. And this is a discussion that we have taken to our internal scientific advisory board several times. And we consistently get the same feedback, which is what -- until you see something that is different or you love something more, at this point, the existing evidence would point to that you need to focus on the T cell in our base therapy.

That's what we are doing. I know that there are a number of companies moving into the NK cells, and we are waiting for the data. Hopefully, at ASH, maybe we'll find something out, and we'll have to see and we haven't had a chance to review the abstract that came out today. But that's more or less our view of the NK cells versus the T cells. And the second question around what you will see at ASH presentation of our UNIVERSAL data. We just sent out another press release. I mean, we're a little bit trying to do a catch-up thing after ASH for (inaudible) releasing the abstract little bit ahead of the schedule. And it will detail what will be presented. I mean, certainly, at this point, as Rafael had commented, we are testing higher lymphodepletion using the higher ALLO-647, some of those data will be included, but in terms of exact details, just give another 6 weeks till you find out.

Our next question comes from Ben Burnett with Stifel.

Question on 715. So the ASH abstract talks about going to higher doses of ALLO-715 beyond the third dose level. I think 480 million cells was mentioned. I wanted to ask, is that planned on being given all at once as a single bolus? Are you going to implement some type of like split dosing strategy? And if that's the case, could you just give a little color around kind of the timing and logistics of the split dose?

In a split dose, it's something that we are not entertaining. So when we talk about a cell dose, I mean, we are sort of planning to -- they will be given as a single infusion.

(Operator Instructions) And that concludes our Q&A session. I would like to turn the conference back over to management for any additional comments.

All right. Thank you very much. Thank you for joining us. I know that today is a very busy time, and thank you for your ongoing support for Allogene. As we look ahead not just an exciting fourth quarter but a busy first half of 2021, we anticipate that you may have additional questions in the days and weeks ahead, so please don't hesitate to reach us to our team, if you were to have any additional questions. And with that, operator, you may now disconnect.

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