Earnings Call Transcript - ALLO Q4 2020

Operator, Operator

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. 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.

Christine Cassiano, Chief Communications Officer

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. After the market closed today, Allogene issued a press release that provides a corporate update and financial results for Q4 and the 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.

David Chang, President and CEO

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 several firsts for Allogene, including 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 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-501A in 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 robust AlloCAR T pipeline toward multiple industry firsts, we are also investing heavily in next-generation technologies designed to keep us at the forefront 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 considerable investments behind TurboCARs, which are 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 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 the 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 choose 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. Additionally, 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 the 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 to announce that last year we received clearance for our IND and are now preparing to launch our TRAVERSE trial. We 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, which we 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 joint venture 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 on 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 this field has sometimes been difficult. However, I personally believe that a rigorous scientific approach is of critical importance for long-term success in the field. Only companies that commit to such scientific excellence and rational decision-making will be able to make the necessary progress to reliably deliver radically transformative and durable therapies to patients. To accomplish such a 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.

Rafael Amado, Executive Vice President of R&D and Chief Medical Officer

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 regarding 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 subsets. 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 lymphodepletion with fludarabine and cyclophosphamide as well as ALLO-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 that 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 protocol 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 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 position us to move on to the next steps in this study, namely optimizing cell dose and lymphodepletion 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 raise 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, and the endpoints being assessed are 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.

Eric Schmidt, Chief Financial Officer

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.

Operator, Operator

And thank you. Our first question comes from Salveen Richter from Goldman Sachs. Your line is now open.

Unidentified Analyst, Analyst

Hi, everyone. This is Andrea on for Salveen. Maybe a question for you, David or for Eric, just with respect to the Overland JV, 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?

David Chang, President and CEO

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?

Eric Schmidt, Chief Financial Officer

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 that 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 commercial rights to all of our products.

Unidentified Analyst, Analyst

Got it, thanks so much.

Biren Amin, Analyst

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?

David Chang, President and CEO

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 easily see occurring in the autologous setting. So as we have done throughout the development of ALLO-501, we are checking every possible lever to optimize and improve what we get with allogeneic cell therapy, starting with cell dose lymphodepletion where we saw very positive findings as we increase the ALLO-647 dose. And what's really left is the consolidation. The details, obviously, with the consolidation are a little complicated, and Rafael went through that. But let me ask Rafael to explain exactly what's being done with the consolidation in 501A.

Rafael Amado, Executive Vice President of R&D and Chief Medical Officer

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. In ALPHA2, it's only large B-cell lymphoma. Patients are enrolled, 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 observed in myeloma is not something that we have seen in lymphoma, which gives a total of 240 million cells. Here, again, as David mentioned, we are trying to see whether we can increase the responses and durability, and we're looking at a variety of biomarkers to give us some surrogate information that this is superior to a single dose.

Biren Amin, Analyst

Great, thank you.

Marc Frahm, Analyst

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?

David Chang, President and CEO

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?

Rafael Amado, Executive Vice President of R&D and Chief Medical Officer

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 used 90 milligrams. 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, we have continued to follow those patients. 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. After that exploration, we commenced the consolidation treatment in ALPHA with enrollment for both follicular and large cell, and in ALPHA2, as I said before, we only enrolled large cell lymphoma. Just to emphasize, the consolidation started much later. It's the last thing that we started exploring. Therefore, the follow-up in those patients will be shorter. So expect longer follow-up from the initial patients from ASCO, additional patients treated with higher doses of ALLO-647, and some data on consolidation.

Marc Frahm, Analyst

Okay, thanks.

Tyler Van Buren, Analyst

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 a lower CRS rate than the other therapies and ICAMs. So I want to ask about the second dose and the propensity or potential for it to possibly increase some of those safety events. And I guess, in the broader context of just using ALLO-647 and not doing conditioning again.

David Chang, President and CEO

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

Tyler Van Buren, Analyst

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?

David Chang, President and CEO

Okay. I got it. My apologies. That's a relatively simple question, and let me take that. I think we are gaining growing information with the redosing. Certainly, in the early days of AlloCAR T, redosing patients after the first dose with Yescarta observed several months later. One thing that was quite noticeable at the time was that redosing was well tolerated among the patients. I think others are seeing a similar trend where dosing is better tolerated in the first time. We don't know what the reason is, but we can speculate; however, that's not important. The way we see it regarding consolidation is more focused on the time window between the first and second dose. Overall, when we look at the data, I feel pretty confident that redosing, as we're doing in the consolidation, will be well tolerated. We're testing that in a Phase I setting, which is the right setting to assess both safety and efficacy.

Tyler Van Buren, Analyst

Thanks for taking the question.

Michael Schmidt, Analyst

Hey, guys. I had a question on your ALLO-316 program that is now starting in Phase I. I guess what type of efficacy and 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 do you think additional optimization may be necessary down the road, maybe similar to what we've been doing with 501?

David Chang, President and CEO

Okay, Michael, thank you for those excellent questions; there are two parts to the question. What are we expecting? In a solid tumor, we must realize that when you look at renal cell cancer, despite all the advances that have occurred over the last decade, complete responses remain very rare. If you look at the history of how the solid tumor is currently managed, it's just prolonging survival from one treatment to another. We are expecting a solid tumor trial with 316 to provide meaningful data. We are looking for more than just response; certainly, whether we achieve a complete remission in solid tumor will be critical. Moreover, among those who get responses, how long does the response last? We have to factor many different elements of what we would consider as meaningful clinical benefit which we believe cell therapy can provide in solid tumors. Thus far, 316 is one of the early allogeneic CAR T programs going into solid tumors, so stay tuned. The second question is essential, regarding what else we can do. There is much innovation awaiting in cell therapy. TurboCAR is one example. TurboCAR constitutes a platform approach whereby we intend to enhance the allogeneic CAR T cells to work better, and we have various preclinical strategies almost ready for the clinic. So stay tuned, but we are definitely planning to innovate continuously from first to second generation, always seeking the best.

John Newman, Analyst

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 ALLO-647?

David Chang, President and CEO

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

Mark Breidenbach, Analyst

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. Would you consider including IL-2 cytokine support, given that IL-2 is already approved in our RCC aside from a future TurboCAR approach?

David Chang, President and CEO

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

Rafael Amado, Executive Vice President of R&D and Chief Medical Officer

Yes, Mark. We are definitely planning to follow a variety of translational parameters. Obviously, the initial information we're seeking is tolerability. So it's a dose escalation trial, but we will look at what happens to these cells. Do they traffic to the tumor, do they encounter the antigen, do they expand, and eventually cause catalysis to the tumor cells? We have contemplated combinations in what is an immunogenic tumor, as you know. Whether it's IL-2 support or PD-1, those are things we may investigate in the future, along with potential modifications of the construct itself. In terms of lymphodepletion, that's an unknown, and we will test that in the Phase I study. One thing I'd note is that CD70 is also expressed in lymphocytes. It's a marker discovered in lymphocytes, and activated lymphocytes might be susceptible to depletion by the CAR. Because of that, we are starting carefully with doses, and we will continue to escalate as we see the program is safe. What's fascinating is what lymphodepletion might be required, considering the target's biology and the tumor's biology, as well as what partner we may need to use with the CAR to ensure efficacy and lead to complete responses.

David Chang, President and CEO

I would just add that the patient's prior treatment history also influences the underlying condition of the immune system, which is relevant as we consider lymphodepletion. We rely on our translational and clinical groups to find answers as we pursue this new path in solid tumors.

Unidentified Analyst, Analyst

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?

David Chang, President and CEO

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

Rafael Amado, Executive Vice President of R&D and Chief Medical Officer

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

Unidentified Analyst, Analyst

Great, thank you.

Lisa Walter, Analyst

This is Lisa Walter on behalf of 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. Do you think that it will just improve the response rate but 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 that data since then, so just wondering if you have any thoughts on this.

David Chang, President and CEO

So Lisa, let me take that question. What we've seen in the field, and I think this is something that has been observed for some time, the data published in the New England Journal of Medicine on the bb2121 indicates that the antigen escape is a relatively infrequent event in multiple myeloma. We will continue to track biology of different tumors. The second question, about antidrug antibodies, is a somewhat more complex response. There are variabilities in how different companies measure antidrug antibodies, and this has been known for some time since the early days of autologous CAR T therapy. Regarding whether antidrug antibodies affect response, I think there's still no evidence that they have any negative consequences. However, we will test this in our studies, and we will look for any evidence of what antidrug antibodies might do to efficacy. So stay tuned.

Ren Benjamin, Analyst

Hey, good afternoon guys, thanks for taking the questions. One for me, just from a manufacturing perspective. Cell Forge 1 is going to be up and running. Can you talk a little about how the products get integrated into the existing trials? Will it come on full-on with the pivotal study? Or will it slowly get integrated? How many facilities do you think you might ultimately have across the US, and what's the capacity?

David Chang, President and CEO

Eric, Cell Forge 1, this is something you are paying close attention to. Do you want to cover the answer about the capacity? And I will follow up to answer the question about integration.

Eric Schmidt, Chief Financial Officer

Yeah, sure. In terms of capacity, Ren, it's a very large facility. As we discussed before, it's 120,000 square feet. The construction is essentially complete. We are now positioning ourselves to activate and operationalize manufacturing in the facility. A lot of efforts and investment have gone into making this a state-of-the-art facility, and we're very proud to see it becoming operational this year. Regarding capacity, we have spoken in the past about being able to commercialize multiple products from this facility on a global basis. It's modular in its design, so it's quite flexible and can definitely accommodate our needs for the foreseeable future. David, back to you.

David Chang, President and CEO

The first question is vital; rephrasing your inquiry: currently, we manufacture CAR cells using contract manufacturers. Now the process will transition to our own facility, Cell Forge 1. How do we guide the clinical studies with varying manufacturing sites? This is something we possess experience in. I personally have experience bringing production from a contract manufacturer to our facility at Kite. In terms of how to do that, a critical factor is characterizing your product, and that's been part of our investment in building our analytical assay capability within our tech ops group. It's a very important question, and I feel confident that we will handle this smoothly.

Carolina Ibanez, Analyst

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 Amado, Executive Vice President of R&D and Chief Medical Officer

Sure. 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 ALLO-715 of which doses are active. In terms of when we will have data, the study just started, and as I said, there's some exploration that we need to do in dose escalation in various parameters. We anticipate having data likely not this year, but early next year. That's our projection.

Sadia Rahman, Analyst

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 about the number of patients we might see treated with both doses of the consolidation regimen? I'm trying to understand how meaningful an update could be, and if there would be enough patients followed at least a month after the second dose to gauge how response rates might improve compared to a single infusion.

David Chang, President and CEO

Excellent question. Let me take the question. As I've said, we're getting close to ASCO time, so we're not going to reveal much detail. However, I would note our study enrollment progress. We have highlighted that since we started these clinical programs across CD19 and BCMA, we have enrolled over 75 patients, and our clinical team is managing enrollment well. We hope to provide a meaningful update, as we have in previous presentations.

Unidentified Analyst, Analyst

Hey, guys. This is Owen on for Dan. Thanks for taking our question. Just one from us on ALLO-715. When discussing redosing patients, can you provide a little more detail on the criteria you are using there?

David Chang, President and CEO

Sure, Rafael, could you respond to that question?

Rafael Amado, Executive Vice President of R&D and Chief Medical Officer

Yes, we have not yet started consolidation in ALLO-715; that's why it wasn't mentioned in the opening remarks. We observed meaningful responses as well as VGPR+, as I mentioned earlier, with 320 million cells. We have completed the dose escalation with ALLO-647 and the cell dose. We are starting the consolidation we've been discussing today. We’re looking forward to starting 605. The next thing to explore in 715 is consolidation, and that is something we look to do. It may be slightly different in design than the ALPHA study due to the nature of the disease, but stay tuned for updates.

Raju Prasad, Analyst

Thanks for taking the question. There has been some discussion in the BCMA space on antigen escape and antidrug antibodies from some of the analyzed autologous data. Can you discuss that aspect and how you anticipate nirogacestat and, importantly, TurboCAR, to help mitigate concerns?

David Chang, President and CEO

Let me take that question. The first question of antigen escape, I think you're referring to BCMA loss. If anything, I think this is something the field has been observing for some time; the data published on the bb2121 suggests that the antigen escape is a relatively infrequent event in multiple myeloma. We will continue to follow the biology of different tumors. Regarding antidrug antibodies, it's a somewhat challenging question to answer because companies measure these differently, and this has been something known for quite a while since early days of autologous CAR T therapy. As for whether antidrug antibodies impact responses, thus far, there's no evidence indicating negative consequences. But this is something we'll be testing in our studies and monitoring any evidence concerning the effect of antidrug antibody on efficacy. So stay tuned.

Asthika Goonewardene, Analyst

Hi guys, good evening and thanks for squeezing me in. I want to talk about expectations for homing and penetration with ALLO-316. I'm wondering if you can discuss what your preclinical experiments show and how you set expectations on that. Also, what kind of persistence do you expect based on preclinical data of 316 in a tumor microenvironment?

David Chang, President and CEO

Rafael, do you want to take that question?

Rafael Amado, Executive Vice President of R&D and Chief Medical Officer

Sure. The product in preclinical studies performs exceptionally well. We conduct various in vitro assays and animal modeling, challenging the product with CD70-positive cells and continue re-challenging to see consistent killing. The persistence diminishes until the cells are re-challenged again, resulting in resurgence. This phenomenon is pronounced for TurboCAR but is also observed in 316. In our animal models, we conducted a range of tests, including PDX models using actual tumors from surgical excisions. We have observed penetration of CAR T-positive cells into the tumor and the stroma with tumor disappearance. If preclinical data is a good omen for clinical outcomes, we are pleased with what we have seen thus far.

David Chang, President and CEO

Thank you for your time. We look forward to more opportunities to share our progress as we advance our CAR T therapies.

Operator, Operator

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