Allogene Therapeutics, Inc. (ALLO) Q4 2020 Earnings Report, Transcript and Summary

Good afternoon, ladies and gentlemen. Thank you for standing by, and welcome to the Allogene Therapeutics Fourth Quarter and Year-end 2020 Conference Call. At this time all participants are in a listen-only mode. 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 conference call over to Christine Cassiano, Chief Communications Officer. Ms. Cassiano, please go ahead.

Thank you, operator. And to all on the line welcome to our first afternoon conference call. As we look ahead to the rest of 2021, we will now be conducting these calls in the afternoon, and we will continue to limit questions to one per person in order to answer all of your questions during the hour. Aftermarket market closed today, Allogene issued a press release that provides a corporate update and financial results for Q4 and full year of 2020. 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. I'll now turn the call over to David.

Thank you, Christine. As we head into our third full year as a company, we are pleased to provide an update on our progress in 2020 and to look ahead at what to expect in 2021. By any measure, 2020 was a standout year for Allogene. We have succeeded in building a company that is capable of highly efficient execution across all research, development, manufacturing and G&A functions. Our strong corporate foundation underpins our ability to deliver meaningful clinical data sets at two major medical meetings in 2020, each of which demonstrated the potential of AlloCAR T therapy and provided proof of concept for our proprietary lymphodepletion platform. We've delivered uninterrupted supply for all clinical trials and have now treated over 75 patients with our allogeneic cell therapies. We believe our clinical experience in the allogeneic field is unparalleled in scope, and we expect our leadership position to widen as we anticipate having five clinical trials underway in 2021. This goal would include full first for Allogene, the TRAVERSE trial, our first solid tumor trial with ALLO-316 in renal cell carcinoma; the UNIVERSAL trial, where we now initiated our first combination of exploring ALLO-715 plus Nirogacestat in multiple myeloma; the IGNITE trial, our first TurboCAR trial investigating ALLO-605 in multiple myeloma; and the ALPHA2 trial, potentially our first pivotal trial with ALLO-501Ain large B cell lymphoma. Our ability to prosecute multiple clinical trials in parallel and the rational optimization strategy that we are pursuing gives us confidence in our ability to overcome hurdles inherent in the allogeneic field. As we advance our increasingly growth AlloCAR T pipeline towards multiple industry first, we are also investing heavily in next-generation technologies designed to keep us at the full front of innovation in the field. As part of these efforts, we have expanded our research to execute on novel strategies designed to increase cell potency, overcome tumor microenvironment considerations and delay immune rejection. We have made a considerable investment behind TurboCARs, a highly innovative and proprietary technology with widespread application. Our initial TurboCARs, which we plan to introduce into the clinic beginning this year, have the ability to increase potency, improve T-cell fitness and augment persistence via the addition of a cytokine stimulation domain. Meanwhile, next-generation TurboCARs are already being designed to overcome immunosuppressive factors in the tumor microenvironment, particularly in solid tumors by engineering T-cell stimulatory domains that are activated by certain factors, such as PD-L1 and TGF beta that normally inhibit T-cell functions. Our focus on new technologies extends to the progress we are making in our partnership with Notch Therapeutics directed at iPSC-derived therapies. Notch is applying its scalable Engineered Thymic Niche platform to develop homogeneous and universally sourced stem cell derived therapies. They have assembled a world class scientific team and are building a fully integrated, rigorously controlled platform for generating and editing immune cells from clonal stem cells to enable development of a range of T-cell therapeutics. While our current focus with Notch is to develop fully functional T-cell therapies for initial applications in non-Hodgkin's lymphoma, leukemia and multiple myeloma, our agreement also gives us the right to pursue natural killer or NK cell therapies, should we opt to do so. Our work allows us to consider next-generation antirejection strategies that might complement our proprietary anti-CD52 platform. We are advancing preclinical programs based on what we call dagger approaches. For example, in concert with Baylor College of Medicine, we are exploring the use of alloimmune defense receptors or ADRs to recognize and destroy alloreactive host immune cells that would otherwise be capable of rejecting the allogeneic CAR T-cells, thereby providing enhanced persistence to allogeneic CAR T cells. In addition, we are advancing cloaking approaches that seek to hide allogeneic cells from detection by the host's immune system. We hope to advance one or more novel strategies into clinic by 2023. Based on the strong foundation we have created, we believe we are in a great position to broaden our reach, both in terms of pursuing new targets as well as expanding our geographic footprint. Let's first talk about new targets. We have previously spoken about our first foray into solid tumors with ALLO-316 in renal cell carcinoma. We believe this disease state is ripe for innovation as current therapies are based on a few mechanistic targets, and complete response rates are low. Our goal is to deliver the potentially transformative impact of CAR T therapy to patients with kidney cancer. We are pleased last year to receive clearance for our IND and are now preparing to launch our TRAVERSE trial. We would expect to share initial data from this trial in 2022. Finally, as we look at both expanding development and our footprint, we are excited about the joint venture we announced late last year with Overland Pharma, named Allogene Overland Biopharm. This first of its kind collaboration for an allogeneic cell therapy will focus on our candidates, targeting BCMA, CD70, FLT3 and DLL3. Not only will this JV give us access to a large and rapidly growing pharmaceutical market in China, but it may also give us the opportunity to accelerate clinical development of certain AlloCAR T pipeline candidates. Based upon my experience over the past eight years of developing successful and lifesaving cell therapies the pursuit of a disciplined, methodical and data driven approach to the most challenging obstacles facing the field of this modality can sometimes be [indiscernible]. However, I personally believe that a rigorous scientific approach is of critical importance to long-term success in the field. Only companies that commit to such scientific excellence and to rational decision-making will be able to make the necessary progress to reliably deliver radically transformative and durable therapies to patients. To accomplish such formidable task, one should surround oneself with a world-class team of scientists, clinicians and cell therapy manufacturing experts. I am blessed to have Dr. Barbra Sasu, our Chief Scientific Officer; Dr. Rafael Amado, our Executive Vice President of Research and Development and Chief Medical Officer; and Dr. Alison Moore, our Chief Technical Officer on the Allogene leadership team, and I'm proud that the teams embrace these same principles. We greatly appreciate your support as we seek to make AlloCAR T therapy accessible to more patients with breast cancer. I will now turn the call over to Rafael for further updates on our research and development activities.

Thank you, David. I'd like to first discuss our CD19 program with ALLO-501 and ALLO-501A in non-Hodgkin's lymphoma. As we look ahead to our next data presentation in a medical forum in Q2 of this year. While our policy has been to not get ahead of meeting announcements to alleviate any speculation with regards to timing, we're targeting ASCO for this update. At ASCO 2020, we presented initial data on 22 non-Hodgkin's lymphoma patients treated with ALLO-501, of which 19 were evaluable for efficacy. Updated ALLO-501 data from the ALPHA trial will reflect longer term follow-up from those patients previously presented as well as more recent data, which will include additional patients who received higher doses of ALLO-647. We will also examine biomarker results such as minimal residual disease or MRD studies. As we expect to have a more meaningful data set, we also intend to provide information on patient subset. As you might recall, our ALLO-501A ALPHA2 trial was defined to potentially move into a pivotal phase, should the data support it. As a result, this trial was designed to enroll a homogeneous patient population focused on relapsed/refractory large B-cell lymphoma. As noted in our press release this afternoon, ALLO-501A was granted fast track designation for the treatment of this population. The aggregated Phase I dose escalation portion of this trial was defined to recapitulate the initial findings from the ALPHA trial with a modified construct where the rituximab recognition domains have been removed. Dose escalation was completed late last year, and as such, durability will be limited from the ALPHA2 trial when data are first presented. As we continue enrollment in this trial, much like the ALPHA trial, we're now focused on enrolling patients into the consolidation portion of this study. For each of these trials, consolidation consists of two infusions of 120 million AlloCAR T cells. The first infusion follows into depletion with fludarabine and cyclophosphamide as well as ALOO-647 and an additional tumor assessment is performed at day 28. If a patient is in complete response, partial response or stable disease at day 28, a second infusion is given approximately five to six weeks after the first infusion. Prior to the second cell infusion, a patient will be eligible to receive a modified lymphodepletion consisting only of ALLO-647. The consolidation protocol will evaluate whether an additional dose of cells can further improve the complete response rate and translate into durable complete responses. As proof autologous CAR T therapies have demonstrated a best overall response rate in the 70% to 80% range. However, over half of these patients fall out of response. The intention of the consolidation protocol is to see if we can potentially induce responses in a higher proportion of patients over the long term. As the duration of follow-up from this consolidation protocols in both ALPHA and ALPHA2 will be short, we look forward to assessing the best course of action for a pivotal trial in the second half of the year. At ASH in December 2020, we were pleased to present the initial data from our ALLO-715 program in relapsed/refractory multiple myeloma. This was the first dataset ever presented on an allogeneic cell therapy targeting BCMA. We were very pleased with the initial look at the UNIVERSAL trial and the proof-of-concept generated by AlloCAR T therapy in this indication. In this initial data readout, 31 patients treated with ALLO-715 were evaluable for safety and 26 patients were evaluable for initial efficacy. As has previously been observed in multiple myeloma, higher CAR T-cell doses were associated with an increased response rate and greater AlloCAR T-cell expansion. In the DL3 cohort of 320 million allow CAR T positive cells the overall response rate was 60% with 40% of patients achieving a very good partial response or better, which we refer to as VGPR+. MRD was assessed in five of six patients with VGPR+ response and all five were MRD-negative. Approximately 90% of patients were treated within five days of study enrollment, and importantly, no bridging therapy was required. In terms of safety, there was no graft-versus-host disease or immune effector cell associated neurotoxicity syndrome observed. Grade 1 or 2 cytokine release syndrome was reported in 14 patients and was manageable with standard therapies. The rate of Grade 3 plus infection events was similar to what has been reported in other advanced multiple myeloma studies. Grade 3 plus adverse events reported as serious adverse events occurred in 19% of patients which included the previously disclosed single Grade 5 event, related to progressive myeloma and a reducing density conditioning regimen. This proof-of-concept data was an important step forward in the field, as an on-demand option may be critical for patients with multiple myeloma, knowing that many either cannot wait for an autologous option or may need to be healthy enough to tolerate and respond to bridging therapy in order to receive autologous CAR T. The findings from the universal Phase I dose escalation trial positions us to move on to the next steps in this study, namely optimizing cell dose into depletion and potentially repeat administration of ALLO-715. Our plan is to provide an update on ALLO-715 later this year. We're also exploring ALLO-715 in combination with the gamma secretase inhibitor, nirogacestat, from our partner SpringWorks Therapeutics. We are pleased to report that we have now initiated this cohort, our first clinical milestone for 2021. Continuing in the BCMA program, we remain on track to submit our IND for ALLO-605 in the IGNITE trial, our first TurboCAR targeting multiple myeloma in the first half of the year. We continue to believe that the innovation behind TurboCAR represents 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 to succeed in harder-to-treat hematologic malignancies and solid tumors and may enable us to brace the bar in multiple myeloma. Lastly, in what is one of our most exciting programs, we're eager to initiate our first solid tumor trial. The TRAVERSE trial with the anti-CD70 CAR T-ALLO 316 in clear cell renal cell carcinoma is initially designed to explore ALLO-316 dosing at 40, 160, 320 and 480 million AlloCAR T positive cells. The protocol will also evaluate components of the lymphodepletion regimen, including ALLO-647, the endpoints being assessed or safety, tolerability, depth and duration of lymphodepletion, cell expansion and antitumor activity. Given the high prevalence of renal cell carcinoma and the lack of curative therapies for advanced disease, we look forward to working closely with leading kidney cancer centers and CAR T specialists in the innovative development of allogeneic cell therapy for this disease. With three trials underway and two more on the horizon, we remain very enthusiastic about our AlloCAR T platform and its potential for patients. I'd like to now turn the call over to Eric to review financials.

Thank you, Rafael and good afternoon. Before I provide a brief overview of our financials for the quarter and year-end, I'd like to spend a few minutes on some of our recent business development activities. In particular, at the end of the year, we announced the formation of Allogene Overland Biopharm, our joint venture with Overland Pharmaceuticals, to develop and commercialize our AlloCAR T therapies in Greater China, Taiwan, South Korea and Singapore. Overland, which is backed by Hillhouse Capital, owns 51% of the joint venture through its investment of $117 million. This investment includes an upfront payment to Allogene of $40 million, the majority of which we expect to book as revenue in Q1 and the commitment of $77 million in capital to support operations at Allogene Overland Biopharm. In addition to the upfront payment, Allogene, which owns 49% of the joint venture, will be eligible to receive approval milestones as well as tiered low to mid-single-digit royalties on in territory net sales. Overland will provide operational support while Allogene will provide technical and manufacturing expertise. Now on to our financials, in the fourth quarter, our research and development expenses were $52.2 million, which includes $7.9 million of non-cash stock-based compensation expense. For the full year 2020, research and development expenses were $193 million, which includes $31.3 million in expenses associated with non-cash stock-based compensation. General and administrative expenses were $17.1 million for the fourth quarter of 2020, which includes $8.6 million of non-cash stock-based compensation expense. For the full year of 2020, G&A expenses were $65.3 million, which includes $34 million of non-cash stock-based compensation expense. Our net loss for the fourth quarter of 2020 was $68.6 million or $0.53 per share, including non-cash stock-based compensation expense of $16.5 million. For the full year of 2020, our net loss was $250.2 million or $2.08 per share, including non-cash stock-based compensation expense of $65.3 million. As we look toward financial guidance for 2021, Dave and Rafael have noted that we expect to have five programs in the clinic, including a potentially pivotal trial for ALLO-501A. To support the advancement of these programs and to prepare for initial GMP production at our Newark manufacturing facility, known as Cell Forge 1, we anticipate that we will need to make substantial incremental investments in R&D. On the other hand, our focus on maintaining an efficient corporate infrastructure should enable more limited growth in G&A spend. Overall, we expect our full year 2021 operating expenses to be between $300 million and $330 million. This includes an estimated non-cash stock-based compensation expense of $80 million to $90 million and excludes any impact from potential future business development activities. With that, we will now open the call to your questions.

And thank you. [Operator Instructions] And our first question comes from Salveen Richter from Goldman Sachs. Your line is now open.

Hi, everyone this is Andrea on for Salveen. Maybe a question for you, David or for Eric, just with respect to the Overland JV, just can you provide additional color on your thinking here? Why the structure was so appealing? And if you think this is a strategy you'll look to employ in other ex US geographies?

Andrea thanks for that question. Obviously, we are very excited about the joint venture that started, and Eric worked very hard on this. So let me ask Eric to explain why we did it the way that we have done with this joint venture. Eric?

Yeah. Thanks, David, and thanks, Andrea, for the question. We are very proud of what we've been able to accomplish here. I think that China is a little bit of a unique market, honestly. One thing that we really liked about China is it's a very large growth opportunity, and it's one where we think manufacturing on the ground can be a huge competitive advantage. So the structure of this joint venture allows us, through our equity position of 49%, to really benefit from the growth in China while we use the influx of capital from our partners at Overland to support much of the build out. So for China, it makes a lot of sense. We'll see in other territories. Obviously, I should reiterate that our focus in the major markets of the US and Europe is really to keep rights commercially to all of our products.

Got it, thanks so much.

Thank you. And our next question comes from Biren Amin from Jefferies. Your line is now open.

Yeah, hi guys. Thanks for taking my question. Regarding the ALPHA2 trial and the consolidation dose of 120 million cell dose. Is that strictly for dose level two? Or would patients be eligible to receive consolidation at dose level three? And are you using a similar consolidation regimen for ALLO-715?

Okay, Biren thanks for that question. We have spoken a little bit about the consolidation but let me just reiterate what we are trying to do with a consolidation regimen, which I think is a very unique opportunity that comes with the allogeneic off the shelf cell therapy. This is not something that I can - I see they can be that easily in the autologous setting. So as we have done throughout the development of 501, I mean, we are checking every hospital levers to optimize and improve what we get with allogeneic cell therapy, starting with a cell dose lymphodepletion where we saw very positive finding as we increase the 647 dose. And what's really left is the consolidation. The details, obviously, with the consolidation is a little bit complicated. And Rafael went through that. But let me ask Rafael to explain exactly what's being done with a consolidation in 501A.

Yeah. Biren, so the consolidation is, as I described in the opening remarks, is where we are enrolling at the moment in both ALPHA and ALPHA2. And in ALPHA2, it's only large B-cell lymphoma. And patients are enrolled. They're treated with the usual lymphodepletion regimen including ALLO-647, and then at day 28, they are assessed. The initial dose is 120 million and the second dose is 120 million. We're not exploring any additional doses because we believe that the dose response that, for instance, tends to be observed in myeloma. It's not something that we have observed in lymphoma, and that gives a dose of - a total of 240 million cells in total. And here, again, as David mentioned, what we're trying to do is to see whether we can increase the responses, increase the durability, and we're looking at a variety of biomarkers to try to give us some surrogate information that this is superior to single dose.

Great, thank you.

Thank you. And our next question comes from Marc Frahm from Cowen & Company. Your line is now open.

Yeah, so thanks for taking my question just focusing back on the ASCO presentation from ALPHA, maybe can you give just a little bit more granularity on how many patients you would expect to be at six months? And then just kind of the relative breakdown of new data in the abstracts versus the presentation itself - like which of those is probably the bigger event that we should be focused on?

All right, Mark. You're going straight into data presentation that we plan to do targeting ASCO. I mean we're getting pretty close. So in terms of what we will say is somewhat limited. But let me ask Rafael to recap what are the salient findings from the ASCO presentation and what has happened over the last essentially about six months since the data presentation, which will be sort of underlying the content of what is to be expected in 2021 ASCO. Rafael?

Sure. So Mark, you may recall that at ASCO, we enrolled 22 patients and as I mentioned before, 19 were eligible for efficacy. We did see dose response rates with regards to ALLO-647 with 50% of patients in complete response when we use 90 milligrams. And so we believe that higher doses of ALLO-647 can cause better lymphodepletion and retard the recovery of endogenous lymphocytes in the patient, and therefore allow for a longer dwelling time of the donor cells. So in the meantime, after that, of course, we have continued to follow those patients. So you can expect a longer follow-up of both the 39 milligrams and the 90-milligram patients. And then we've continued to explore the higher doses of ALLO-647 as a single dose. We've treated a number of patients at that dose. And then after that exploration, then we commenced the consolidation treatment in ALPHA with enroll both follicular and large cell, and in ALPHA2, as I said before, we only enrolled large cell lymphoma. And then just to make the point that the consolidation started much later, obviously. It's the last thing that we started exploring. And therefore, the follow-up in those patients will be naturally shorter. So you can expect longer follow-up from the initial patients from ASCO, additional patients treated with higher doses of ALLO-647, and data - some data on consolidation.

Okay, thanks.

Thank you. And our next question comes from Tyler Van Buren from Piper Sandler. Your line is open.

Hey, guys thanks. Good afternoon. I just wanted to focus on the second dose, specifically, with the consolidated dosing regimen. Previously at the last data update, you guys showed lower CRS rate than the other therapies and ICAMs. And so I want to ask about the second dose and the propensity or the potential for it to potentially increase some of those safety events. And I guess in the broader context of just using ALLO-647 and not doing conditioning again.

So Tyler, I'm trying to better understand the question. Rafael, as he stated - I mean the second dose is the same as the first cell dose of 120 million cells. So the question is around why 120? Or I want to better understand exactly what you're asking.

Sorry. Does the second dose add new safety events or make tolerability worse based upon your experience of patients that you've dosed with a consolidated dosing regimen to date.

Okay. I got it. My apologies. I think that's a relatively simple question and let me take that. I mean I think we are getting to have growing information with the redosing, certainly in the days of early AlloCAR T where - when we were redosing patients after first dose with Yescarta and the several months later. And one thing that was quite noticeable at the time was redosing was relatively well tolerated among the patients. And I think not just us, others are seeing similar trend where we dosing is much better tolerated in the first time. We don't know what the reason is, but I think there are many things that we can speculate, but that's not important. The way we see it in terms of consolidation, it's more concentrated in terms of the time window between first and second dose. But overall, when we look at the data and based on all my experience, I feel pretty confident that redosing, as we're doing in the consolidation will be relatively well tolerated. And certainly, we are testing that in a Phase I setting, which is the right setting to really assess both safety and efficacy.

Thanks for taking the question.

Thank you. And our next question comes from Michael Schmidt from Guggenheim. Your line is now open.

Hey, guys I had a question on your ALLO-316 program that is now starting in Phase I. I guess what type of efficacy safety profile do you think might be necessary for this in the solid tumor context, specifically in RCC, to ultimately be successful at a minimum? And to what degree do you think this could be achieved with this product candidate already? Or whether you think additional optimization may be necessary down the road, maybe similar to what we've been doing with 501?

Okay. Michael, thank you for those excellent questions, I mean there are two parts to the question. I mean one is really what will - what are we expecting? I mean in a solid tumor, we have to realize, when you look at the renal cell cancer, despite all the advances that has occurred over the last decade, still, complete responses are very rare. I mean if you look at the history of how the solid tumor is currently managed? It's just buying additional time from one treatment to another and continuing that. What we - what to expect from the solid tumor trial with 316, which we are very excited about, I mean I think time will tell. I think we are looking at more than just response. Certainly, whether we get a complete remission in solid tumor that will be a very important information. And second one is really among stores who get responses, how long does the response lasts? So I think we have to factor many different elements of what we would consider as a meaningful clinical benefit which we can - we believe that cell therapy can provide in solid tumors. So 316 is one of the early and probably the first allogeneic CAR T programs that is going into the solid tumor, so stay tuned. The second question is really an important question. What else can we do? Certainly, there is a lot of innovation that's awaiting to occur in the cell therapy space. TurboCAR is one of them. And TurboCAR is actually a platform approach that we are making to make the allogeneic CAR T cells to work better, and we have several different tricks that we are exploring in the preclinical setting that's almost ready to go into the clinic. So stay tuned, but we are definitely planning to continue to innovate from the first generation to second generation, always looking for the best.

Thank you.

And thank you. And our next question comes from John Newman from Canaccord. Your line is now open.

Hi, guys thanks for taking my question. Question is regarding the ALLO-715 plus nirogacestat cohort. I'm just curious, David, if you have an opportunity or if there would be perhaps a need to explore different dose levels of nirogacestat in the future? Or if it's more likely that you might simply continue to explore higher doses of 647?

Great question. That's why we are doing these things in a Phase I setting where we have the option of exploring different things, and the question of whether to explore different doses of gamma secretase inhibitor or different doses of cell therapy, that's really fundamental to any combination therapies that are being tested. I mean the hypothesis for this combination study is very straightforward, and the way that the study is designed, it gives us optionality to explore different doses of gamma secretase inhibitors. So we are very excited in - that we were able to clear the IND in a record time and also in the process of activating the sites. So this is - these are the questions that we will know in very near future. So stay tuned.

Great, thank you.

Thank you. And our next question comes from Mark Breidenbach from Oppenheimer. Your line is now open.

Hey guys, thanks for taking the question I wanted to jump back to ALLO-316 for a second in the TRAVERSE trial. I'm wondering if you think you'll need to identify distinct lymphodepletion conditions that are very different from what seems to be working in human settings. And would you consider including IL-2 cytokine support, given that IL-2 is already approved in our RCC aside from a future TurboCAR approach?

Yeah. I always get amazed about the sophisticated questions that you're asking. Let me ask Rafael to answer those very important questions. Rafael?

Yes, Mark. So I mean we are definitely planning to follow a variety of translational parameters. Obviously, the initial information that we're seeking is tolerability. So it's a dose escalation trial. But we will be looking at what happens to these cells, do the traffic to the tumor, do they encounter antigen, do they expand and eventually costs catalyzes to the tumor cells. We have thought about combinations, which is an immunogenic tumor, as you know. And whether it's IL-2 support or PD-1, those are things that may come in the future, along with potential modifications of the construct itself, such as what David was referring to before. In terms of the lymphodepletion, that's an unknown, and we will be testing that in the Phase I study. One thing that I would say is that CD70 is also in lymphocytes. It's actually a market that was discovering lymphocytes, and it's actually expressed in activated lymphocytes. So it is possible that all reactive lymphocytes may be susceptible to depletion by the CAR. So because of that, we are obviously starting carefully with doses, and then we will continue to escalate as we see that the program is safe. So it's a fascinating question, what kind of lymphodepletion we will need because of the biology of the target. And as well as the biology of the tumor, what kind of partner perhaps we will need to be using with the CAR to make it effective and lead to complete responses.

Yeah. And I would just add, besides those, the patient's prior treatment history, that also influences patients' underlying basal on conditions about the immune system, which is relevant as we think about the lymphodepletion. So we rely on a lot on our translational and clinical groups to find answers to these important questions as we are studying - taking a new path in solid tumors.

Super, thank you.

And thank you. And our next question comes from Cory Kasimov from JP Morgan. Your line is now open.

Hey guys thanks for taking my question. This is Matthew on for Cory. Just a quick one for me, can you remind us if you're looking at anti-CAR antibodies in your ALPHA and ALPHA2 studies and whether we might get some of this data at ASCO?

Okay. Yeah, Rafael, do you want to cover that?

Yes. Just very simply, we are looking, and we plan to disclose a variety of translational markers, including anti-CAR antibodies.

Great, thank you.

Thank you. And our next question comes from Luca Issi from RBC. Your line is now open.

This is Lisa Walter on Luca Issi from RBC. Just wanted to continue the conversation on the gamma secretase inhibitors, so again, the gamma secretase obviously induces the expression of BCMA. So do you think that it will just improve the response rate but not - maybe not necessarily the duration of response? The reason I'm asking is because we've seen some impressive data from Fred Hutch at ASH 2019, but we haven't seen an update on the data since then, so just wondering if you have any thoughts on this.

So Lisa, let me take that question. What the field has seen - and I think this is something that we have seen from the early days in CAR T trial where others who generate the data keep - find a similar pattern. One, cell expansion tends to correlate with the response and response, especially the depth of response, and to correlate with the durability of the response. So one of the sort of underlying hypothesis that we want to test in the combination study is as we increase the density of the BCMA on the multiple myeloma cells, can we get a deep response. So response, as you know, partial response, very good partial response, complete remission, stringent complete response and also MRD status. I think all these are different levels of responses that we can look into, and I think that will tell quite a bit. And the question about response of - and the durability, they are somewhat linked in the cell therapy in my experience, so excellent question. The second part to your question about updates from Fred Hutch, I don't know what's going on there. Hopefully, they will update in - sometime in the near future. But this is a very interesting hypothesis, and this is a very interesting concept that we feel that we have to test as we advance our BCMA CAR programs in multiple myeloma.

Great, thanks for taking my question.

Thank you. And our next question comes from Ren Benjamin from JMP Securities. Your line is now open.

Hey, good afternoon guys thanks for taking the questions. I guess one for me, just from a manufacturing perspective. Cell Forge 1 is going to be up and running. Can you just talk a little bit about how the products get integrated into the existing trials? Does it kind of just come on full on with the pivotal study? Or slowly get integrated? How many facilities, do you think? How many cell forges do you think you might ultimately have across the US as well? And what's the capacity?

Eric, Cell Forge 1, this is something that you're paying close attention to. Do you want to cover the answer about the capacity? And I'll come back in and answer the questions about integration.

Yeah. Sure. Okay. I mean in terms of capacity, Ren, it's a very large facility. I think as we've talked before, its 120,000 square feet. The construction is essentially complete, and we're now in a position where we can begin to activate and operationalize manufacturing in the facility. So a lot of efforts, a lot of investment has gone in to make this state-of-the-art facility, and we're very proud of its becoming operational this year. In terms of the capacity, we've spoken in the past about being able to commercialize on a global basis, multiple products from this facility. It's modular in its design, so it's quite flexible and quite large and can certainly suit us for the foreseeable future. David, back to you.

Yeah. So the first question is a very important one, which is really - rephrasing your question, right now, we are making the cell CAR using the contract manufacturer. Now you have the process going over to our own facility, Cell Forge 1. How do you source the clinical studies with a different site manufacturing? I mean this is something that we have - I personally have a lot of experience having done that at Kite where we went from the contract manufacturer to our own manufacturing facility. And in terms of how to do that and what's also required, part of which is being able to characterize your product, analytic assay capability, which we have been building internally within our tech ops group. So a very important question, something that we have a lot of experiences in, and I feel very confident that we will be able to handle this very smoothly.

Perfect, thank you.

Thank you. And our next question comes from Ben Burnett from Stifel. Your line is now open.

Hi, good afternoon. This is Carolina Ibanez on for Ben Burnett. As a follow-up to the previous questions on ALLO-715 in combination with nirogacestat, can you provide additional details on the type of patients you are enrolling, whether or not you plan to test both low and high dose, ALLO-647? And when do you expect to have initial data?

Rafael?

Sure. So the study is exploring ALLO-647 and also doses of nirogacestat as well. The cell dose is going to be relatively fixed. We will study a limited number of cell doses because we have an idea from 715 of what doses are active. In terms of when we will have data on this, I mean the study just started, and as I said, there's some exploration that we need to do in dose escalation in a variety of parameters. So we anticipate to have data probably not this year, but early next year. That's our projection.

Thank you. And our next question comes from Jason Gerberry from Bank of America. Your line is now open.

Hi, this is Sadia Rahman on for Jason. For the CD19 update at ASCO, I know you started enrolling pretty recently. So can you talk about the pace of enrollment and give some idea on the number of patients we might see that are treated with both doses of the consolidation regimen? I'm trying to understand how meaningful update could be, and if there be enough patients followed at least a month after the second dose to gauge how response rates might improve compared to the single infusion.

Excellent question. Let me - this is David. Let me take the question. As I've said, we're getting pretty close to ASCO time, so we're not going to go too much into the details. But I would sort of look at our record of study enrollment. We have highlighted the fact that since we that - since we started the clinical programs across CD19 and BCMA, we have enrolled 75 plus patients, and we have an outstanding clinical team that is managing the enrollment and also patient with a lot of issues. So we are still enrolling, and we are hoping that we can provide a meaningful update as we have done in the past two presentations.

Okay, thank you.

Thank you. And our next question comes from Dane Leone from Raymond James. Your line is now open.

Hey, guys. This is Owen on for Dan. Thanks for taking our question. Just one from us on ALLO-715, so when we're talking about redosing patients, can you just give a little bit more color on the criteria you would be using there?

Okay. Rafael - I would ask Rafael to respond to the question.

Yes. So we have not yet started consolidation in the ALLO-715, that's why it wasn't mentioned in the opening remarks. We saw meaningful responses as well as VGPR plus, as I've mentioned earlier in the 60% or 40%, respectively, with 320 million cells. And now we have finished the dose escalation with the ALLO-647 as well as the cell dose. So we're starting the [indiscernible] status we've been discussing today. We're looking forward to start 605. And the next thing to explore in 715 is consolidation and that is something that we're looking forward to doing. It may be slightly different in design than the ALPHA study due to the nature of the disease but stay tuned to that in an upcoming update.

Great, thank you.

Thank you. And our next question comes from Raju Prasad from William Blair. Your line is now open.

Thanks for taking the question. There's been some discussion in the BCMA space on antigen escape and antidrug antibodies from some of the autologous data that's been analyzed. Can you maybe just talk a little bit about that aspect? And how you anticipate nirogacestat, and more importantly, the TurboCAR to potentially help mitigate kind of some of those potential concerns?

Yeah. Let me take that question. I think the first question of the antigen escape, which is BCMA loss that I think you're referring to. If anything - I mean I think this is something that the field has been looking for some time, and also the data that was published in New England Journal of Medicine on the bb2121, it certainly tells you that the antigen escape is relatively infrequent event in multiple myeloma. So obviously, we are learning about the biology of different tumors, but that's the status of it. And we will continue to follow in our study about the occurrence of the antigen loss. The second question around the antidrug antibody, that is somewhat difficult to respond to because there are some variabilities in how different companies are measuring antidrug antibodies, and this is something that we knew for some time from the early days of autologous CAR T therapy. In terms of whether the antidrug antibodies affect the response and all those things, I think at this point, there's no evidence that antidrug antibodies have any negative consequences. But this is something that we will be testing in our own studies, and we will look for any evidence of what the antidrug antibody, if it occurs, will do to the efficacy. So stay tuned.

Thank you. And our next question comes from Asthika Goonewardene from Truist Securities. Your line is now open.

Hi guys, good evening and thanks for squeezing me in. So I want to talk a little bit about expectations for homing and penetration with ALLO-316. I'm wondering if you can discuss what your pre-clinical experiments have shown you and how you set expectations that. And also what kind of persistence you expect based on pre-clinical data of 316 in a tumor microenvironment?

Rafael, do you want to take that question?

Sure. So the product in preclinical studies performs incredibly well. So we do a variety of in vitro assets as well as animal modeling in, in vitro assays, we obviously challenge the product with CD70 positive cells and we continue to re-challenge, and we continue to see killing. The cells diminish, in terms of persistence, until they get re-challenged again and then you see again a resurgence. This is more pronounced in general in the case TurboCAR, but it's seen also in 316. In our animal models, we have done a variety of them, including PDX model that is animals in - immunocompromised animals that contain human tumors, and we've seen penetration of the CAR T positive cells into the tumor into the stroma and disappearance of these tumors. And again, these are not xenograft or cell lines, these are actual cells - or tumors rather that come from metastases procure from surgical excisions. So if the preclinical data is good omen to what's going to happen in the clinic, we are pretty pleased with what we've seen thus far.

Great, thank you.

Thank you. And I would now like to turn the call back over to management for closing remarks.

Thank you for joining us on our earnings call and for many outstanding questions. As we close out the call, I'd like to thank our team at Allogene and our many partners and collaborators who overcame the global challenges of 2020 to make the progress we highlight today possible. Operator, you may now disconnect.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating, and you may now disconnect. Everyone, have a great day.