Allogene Therapeutics, Inc. (ALLO) Q3 2019 Earnings Report, Transcript and Summary

Good morning, ladies and gentlemen, and thank you for standing by. And welcome to Allogene Therapeutics Third Quarter 2019 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 advised today’s conference will be recorded. I would like to turn the conference over to Christine Cassiano, Chief Communications Officer. Ms. Cassiano, you may go ahead.

Thank you, operator, and good morning. Before market opened today, Allogene issued two press releases. One press release discusses an exclusive collaboration with Notch Therapeutics to develop iPSC-based AlloCAR therapies, and the other provides a corporate update and financial results for the quarter ending September 30, 2019. The press releases are available on our website, at www.allogene.com. We remind listeners that 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. Eric Schmidt, Chief Financial Officer; and Dr. Rafael Amado, Executive Vice President of Research and Development and Chief Medical 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, regulatory filings, future research and development efforts, and manufacturing capabilities, among other things. These forward-looking statements are based on current information, assumptions and expectations that are subject to change and involve a number of 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 June 30, 2019 as well as our upcoming Form 10-Q for the quarter ended September 30, 2019. You are cautioned not to place undue reliance on these forward-looking statements, and the company disclaims any obligation to update such statements. I’ll now turn the call over to Dr. David Chang.

Good morning and our thanks for joining us on our call today to discuss our third quarter and recent events. As we complete the end of our first full year in operation as a public company, I am very pleased with what we have accomplished at Allogene. While we were able to leverage the great research from Pfizer to give us a strong foundation, we have built Allogene from the ground up, by assembling world-class capabilities across all functions. We have successfully progressed 2 AlloCAR T programs into clinic, advanced pipeline programs toward potential IND, and optimized current AlloCAR T manufacturing, while creating next and future generation therapies. We have initiated the build out of in-house manufacturing capabilities. We have also completed our new headquarters, which now house both the R&D and G&A functions under one roof. To that end, I would like to thank those who joined us in September for our Open House at our new headquarters. We were pleased to have so many analysts, investors, collaborators and friends of Allogene join us in celebration and visit our new labs. During the event, I spoke about our journey from company inception to today, where we are now in position to treat patients with refractory hematological malignancies under 2 active INDs. I believe that the investment Allogene is making in facilities, manufacturing and personnel provide us with the key building block to support our next phase of growth, as we seek to advance AlloCAR T therapies through clinical development and toward commercialization. As many of you know, our next phase of growth includes the construction of our state-of-the-art manufacturing facility in New York, California. On our last quarterly call, we announced that Dr. Rafael Amado would be joining our Allogene team. Since his arrive in early September, his leadership of the Research and Development team and integration with other cross-functional teams have been seamless. Rafael’s familiarity in engineered cell therapy allowed him to quickly step into the role of head of R&D and support us in refining the R&D strategy. I look forward to giving Rafael the opportunity to update you more fully on these efforts later in this call. We are now firmly into the clinical stage of development with lead pipeline programs. We have checked off the last of our stated 2019 program milestones, as we are treating patients with the initiation of our ALLO-715 clinical trial in multiple myeloma and in our ongoing ALLO-501 ALPHA trial in non-Hodgkin lymphoma. As we have previously stated, we plan to share the data from the ALLO-501 Phase 1 trial in the first half of 2020. We are committed to readily moving our therapies to clinical trials and advancing this nascent field of allogeneic cell therapy to generate viable commercial therapies for patients in need. We can use our firsthand knowledge and growing industry insights of autologous cell therapy to advance allogeneic development. But as we have all learned to appreciate the allogeneic cell therapy is fundamentally different than autologous cell therapy. To that end, our translational team is highly focused on building a robust understanding of the relationship between lymphodepletion and cell expansion, and ultimately, clinical outcomes including, both safety and efficacy. Turning your attention to our other news this morning, our collaboration with Notch Therapeutics is part of our broader long-term strategy to think beyond what can be achieved with currently available technologies underlying the first and second generation CAR T therapies. While we believe our initial AlloCAR T programs derived from cells collected from healthy donors have the potential to revolutionize the field by making CAR T therapy available to many more patients, innovation cannot stop there. We are excited to partner with Notch to develop the next generation of AlloCAR T therapies derived from induced Pluripotent Stem Cell or iPSCs. We believe this exclusive world-wide collaboration and licensing agreement with Notch, utilizing Notch’s Engineered Thymic Niche iPSC-based platform, has the potential to create novel cell-based therapies that feature improved efficiency of gene-editing, greater scalability of supply, product homogeneity and more streamlined manufacturing. Our collaboration with Notch includes exclusive rights to use iPSC technology to develop, engineer T cells or Natural Killer, and K cell therapies across multiple targets in oncology and other diseases with initial application focused on B cell malignancies and multiple myeloma. One of the most important aspects of this collaboration is the ability to work with scientific luminaries, Dr. Juan Carlos Zúñiga-Pflücker and Peter Zandstra, the founders of Notch Therapeutics. JC and Peter are well known in the iPSC field for their pioneering work in developing techniques for differentiating iPSCs into T cell and other immune cells. Given our confidence in the team and strategic interest in the technology, we have also acquired a 25% equity position in Notch. Eric will review the financial details from this agreement later in this call. It is now my pleasure to warmly welcome Rafael, who will update you on recent research and development activities.

Thank you, David, and good morning to all of you on the call today. In my previous role, I’ve had the pleasure of speaking with many of you, but today I am very happy to be speaking on behalf of Allogene and representing the work that has been underway by an excellent team of people in R&D. Well, I just recently joined Allogene in September, I was fortunate to have an opportunity to meet some of you at our open house and at various investor events. Thank you for the warm welcome and look forward to many more opportunities to see you in the months and years to come. Our ALLO-501 ALPHA dose escalation study continues to accrue as planned. We will also be filing an amendment to the current protocol for the ALPHA trial to further explore the optimal dosing schedule of ALLO-647. ALLO redosing of patients and expand enrollment criteria to include patients who have been previously treated with autologous CD19 directed therapy and whose disease have progressed. We are studying a variety of corollary parameters that are informing us about the optimal relationship between the depth of lymphodepletion, cell dose and clinical outcomes as David mentioned earlier. Indeed, we have made a lot of progress in setting up clinical translational [assays] [ph] both internally and externally to fully elucidate the optimal conditions that will lead to best outcomes in the allogeneic setting. This work is being done in close collaboration with the research and the process development team that will supply the key properties of the allograft associated with optimal pharmacodynamic and clinical properties. We initiated our ALLO-715 UNIVERSAL clinical trial during Q3, and we’re actively accruing and treating patients. We are developing ALLO-715, our anti-BCMA allogeneic CAR T therapy for the treatment of relapsed/refractory multiple myeloma patients. We continue to get many questions about ALLO-715 UNIVERSAL trial, so I’d like to briefly remind you of its design. The Phase 1 study is designed to assess the safety and tolerability of increasing dose levels of ALLO-715 with a goal of identifying an optimal dose of ALLO-715 for the potential Phase 2 study, which could be a pivotal study for a BLA submission. As do the AlloCAR T CD19 studies, this trial will also utilize ALLO-647, our proprietary anti-CD52 monoclonal antibody as a part of the lymphodepletion regimen. In the main portion of the study, we plan to enroll up to 24 patients with relapsed/refractory multiple myeloma, who had failed at least 3 prior lines of therapies in a dose escalation 3 plus 3 trial design. The UNIVERSAL study designed to allow for exploration of additional cohorts to assess a potential milder lymphodepletion regimens where the chemotherapy component specifically fludarabine and cyclophosphamide will be stepwise removed. As we look ahead, we will be assessing endpoint such as safety, tolerability, cell expansion and anti-tumor activity as key determinants of success for ALLO-715 with a various lymphodepletion regimen. We anticipate sharing a first look of the data from this trial by the end of 2020. We’re also pleased to announced that Servier, our development partners on UCART19 continue to expect moving that pediatric and adult trials in ALL into Phase 2 in 2020. We remain very excited about the strategic direction and progress of our research and clinical programs. We’re uniquely fortunate to have access to what I believe is one of the very best scientific advisory boards in the industry, and my first Scientific Advisory Board meeting at Allogene showcase pioneering science in the allogeneic cell therapy space and what’s one of the most productive SABs that I have ever attended. This expansive meeting sort feedback on our pipeline in the design of our trial and the innovations that are the focus of our research team including new products and innovative technology to address hematologic malignancies and solid tumors. We have already highlighted some of the work we are pursuing, including the research collaboration with Stanford University signed in September. Under this collaboration, Allogene in partnership with researchers, Dr. Robert Waymouth, Dr. Paul Wender, and Dr. Ronald Levy will investigate a novel nucleic acid delivery system to more effectively, safely and flexibly deliver RNA or DNA into lymphocytes, including T cells to allow efficient genetic engineering ex vivo. I am also very excited by the internal innovation that our teams are pursuing. The validation on guidance would we see from our SABs invaluable and we look forward to unveiling more projects from our research efforts over the next year. I will now like to turn the call over to Eric.

Thank you, Rafael. I will provide a brief overview of Allogene’s financials. Additional detail on our third quarter financial results can be found in our press release issued earlier today and in our 10-Q, which will be filed with the SEC. We remain strong financially with cash, cash equivalents and investments totaling $601.9 million as of September 30, 2019. In the third quarter, our research and development expenses were $40.0 million, which includes $5.5 million of non-cash stock-based compensation expense. R&D expense in Q3 also includes a $5 million milestone payment to our partner Cellectis, which is associated with the initiation of the Universal study on ALLO-715. General and administrative expenses were $15.0 million for the third quarter of 2019, which includes a $7.3 million non-cash stock-based compensation expense. Our net loss for the third quarter of 2019 was $50.7 million, or $0.50 per share including non-cash stock-based compensation expense of $12.8 million. As we’ve noted in previous quarters, we continue to invest heavily in our clinical programs and advancing the build out of our manufacturing capabilities as well as hiring the cross functions with now 190 full time employees. We’ve also been highly focused on executing strategic business development agreements. As noted earlier in this call, we are very excited about our exclusive collaboration with Notch and the ability to develop next generation iPSC-based allogeneic therapies. Under the terms of the agreement, Allogene will provide an upfront payment of $10 million, research funding over the collaboration term and a preferred equity investment of $5 million in return for a 25% equity position at Notch. Pre-clinical research will be conducted by Notch under the direction of joint development committee. Allogene will lead the clinical development and commercialization of all candidates that may come out of the collaboration and will retain worldwide rights to any potential candidates. Notch would be eligible to receive future payments upon achievement of certain research, development and commercial milestones as well as tiered royalties. Including the expenses associated with the Notch transaction, we remain in position to reiterate our 2019 net loss guidance. Full-year net losses are expected to be between $200 million and $210 million. This includes an estimated non-cash stock based compensation expense of $45 million to $50 million. With that brief review of our financials, we will now open the call for your questions.

Thank you. [Operator Instructions] Our first question comes from Biren Amin with Jefferies. Your line is now open.

Yeah, hi, guys. Thanks for taking my questions and congrats on all the progress. Maybe if I could start with ALLO-501, can you just talk a little bit about how many patients you would have at the time of data in first half of 2020, David? And, I guess, based on that analysis, what would be potential next steps?

Biren, we’ll be happy to answer those questions. And I’m going to direct your questions to Dr. Rafael Amado.

Yeah, hi, Biren. So the trial is progressing quite well as planned. We decided that our first presentation would be one that contains enough information to be able to evaluate the allogeneic approach. And we will continue guiding to the same time, which is the first half of this year. So our expectation is that we will have enough patients to be able to make statements about efficacy, safety and corollary parameters.

Thank you. Our next comes from Phil Nadeau with Cowen and Company. Your line is now open.

Good morning. Thanks for taking my question. My question is also on the ALLO-501 ALPHA Trial. During you prepared remarks, you mentioned a couple of times that you were working to figure out how the depth of lymphodepletion affects cell expansion. And in fact from the ALPHA Trial, you mentioned that you’re going to change the dosing schedule of 647. So can we read into those comments that you’ve started to investigate these changes because of what you’ve seen in the initial patients? And, I guess, specifically what dosing schedule change are you contemplating for 647 and what are you trying to accomplish? Thanks.

Yeah, Phil. Good morning. Let me take that question. This is David Chang. So some of the questions about things that we are looking at, I mean, this is a Phase 1 study. And we always view the Phase 1 study to really test unknowns as well as to confirm some of the assumptions that went into the design of the Phase 1. And in Phase 1, as we have talked about, flexibility of the key, because there are so many different questions that we want to ask. And at the end, the goal of Phase 1 is coming up with the right doses and schedule that will enable us to move into the Phase 2 and progress on the Phase 2 as quickly as possible. So a lot of times, in Phase 1, from the beginning sometimes starts with a lot of flexibility. In the case of ALLO-501 ALPHA study, given that it is our first clinical study as a company, we elected to go with a very simple protocol and take the opportunity to amend the studies as it goes. So none of these, the things that we are talking about is a reflection of what we are seeing. But it is all part of the original plan that we had.

Thank you. Our next question comes from Cory Kasimov with JPMorgan. Your line is now open.

Hi, this is Galvin on for Cory. Just wanted to get your thoughts on the Notch deal, kind of what drove the decision there? Did you see, was it clinical or any pre-clinical data; and just any thoughts on the timing, why did you decide to do the deal now? Thanks.

Yeah, this is David Chang. Let me take that. I mean, I think we have talked about how we are thinking about the CAR T therapy in general several times. This is the field that started from the oncologists. And now, we are trying to advance that into the allogeneic using the healthy donor. And we also have talked numerous times about where the future may lie, as we advance the allogeneic CAR T therapy. And we believe that eventually using the iPSC-derived renewable cell source has the potential to really fine-tune the gene-engineering as well as making the manufacturing more scalable. So you may say, why now? I think this is something that we always have to be somewhat opportunistic. And some of the reasons that drove us to this deal is, I believe that scientific founders of Notch, this is Dr. JC Zúñiga and then also Dr. Peter Zandstra. I mean, so these two scientific founders. I mean, they really define the differentiation of iPSC into the T cells. And so far, the platform that they are bringing, the [ENT] [ph] platform or the Engineered – Notch’s Engineered Thymic Niche really provides us a serum-free [cell-free based] [ph] synthetic platform that allows the differentiation of iPSC as a functioning T cell. And that’s really what drove us to get in to this deal. Scientific founders, what they have and what we believe to be a scalable and potentially more GMP amenable manufacturing process.

Thank you. Our next question comes from Tyler Van Buren with Piper Jaffray. Your line is now open.

Hey, good morning, guys. Congratulations on all the progress during the quarter. Just had another question, regarding an amendment that was discussed in the prepared remarks with your guy’s decision to include patients who are previously treated with CD19. I was just curious what resulted in that change, if there are any observations pre-clinically or clinically that you’re willing to talk about.

Yeah, hi, this is Rafael. So as we’re progressing the study, we’ve been thinking about ways to potentially test the allogeneic approach in other settings. So as you know, in Non-Hodgkin Lymphoma, although the outcomes are excellent for patients that have no other options, there are still two-thirds of patients that don’t benefit. And there are patients that progress really quickly or don’t respond within the first 3 months. And many of those patients actually have poor graph. Although any release requirement, the T cells are either exhausted or they don’t have the right phenotype. And so, we saw that, provided that the base tumor was still CD19. And that the [CARTA what is] [ph] before had a different single chain V, trying an allogeneic approach in these patients would make sense. It would be, first of all, source of patients, but also more importantly, a proof of concept as to whether allogeneic therapy can work in patients that have failed autologous therapy, which is, I think something that would be of very benefit to the field. So that was the rationale, the rationale behind it, and particularly knowing that this is a sizeable patient population that once they fail autologous CAR T, they have very few options.

Thank you. Our next question comes from Amanda Murphy with BTIG. Your line is now open.

Hi, good morning. And just so you had a question on 501 as well, curious, I don’t know if you’ve been able to talk to the centers and get a sense, to the extent that you do get complete responses, how are the physicians thinking about transplant in this setting? Do you have any sense if they’ll go to transplant or try to see how long the CAR T or the durability of the CAR T can last?

Amanda, this is David. Let me take your question. Good morning.

Hi.

So as we do the study, I mean, we have to act very closely with the investigators. And some of the amendment that we have talked about, that also factors into investigators’ interest and advice that we are getting from them. And as Rafael just have talked about, the inclusion of the patients who previously received CD19, it reflects the growing interest in the field as identifying the previously treated patients who previously received CD19 CAR T as an autologous treatment and have not responded as being of one unmet need. So we are definitely interested in sort of going with the investigator and pursuing that avenue. With respect to the other things, I mean, I’d say the support of the investigator and the rate of enrollment, I mean, I think this is very much preceding according to the plan, and I cannot be happy with how they’re progressing with the clinical studies. I mean, I know that many of you are asking questions about what we are seeing in the clinical study. And this one, we’re going to really make in the position that we have been maintaining over the last 3 quarters, which is that we would like really provide a meaningful update in due time. And we project as we have stated in the prepared statement to be in the first half of 2020.

Thank you. Our next question comes from Mark Breidenbach with Oppenheimer. Your line is now open.

Hey, good morning, guys. Let me ask a 2 part question if I can. First of all, do you think that the exploratory lymphodepletion regimens that are being amended into the ALPHA protocol are going to be very similar to what’s being tested in UNIVERSAL? Or do you think that the 2 protocols will diverge from each other in terms of lymphodepletion regimen? And the second part of the question really is focusing on the Notch collaboration. It sounds like Notch has core technology focuses on program differentiation of iPSCs in the T cells and maybe NK cells as well. But I’m wondering, if I also have a proprietary methodology for iPSC induction. And if so, can you just quickly comment on how that avoids treading on some of the existing IP that’s out there from Notch’s competitors? Thank you.

So let me – Mark, let me take both of those questions. The first question about some of the expiration that we are doing in the 501 study with respect to the lymphodepletion, I mean, this is one of the key areas of the allogeneic, how to do proper lymphodepletion that will control the reduction of AlloCAR T, which is something that have to be overcome for the any allogeneic CAR T therapy to work. And we are using essentially what has built as a selective biological lymphodepleting agent, our ALLO-647, which really gives us a many different ways to think about the lymphodepletion, some of that we have outlined as you’ve pointed out in our ALLO-715 UNIVERSAL study. And in the 501 study, we are sort of testing it, exactly, how we are doing it, I don’t think, it’s – this is the right place to go into it. But conceptually, both programs will test and reveal different modifications that we can do with ALLO-647, so how the key things that we are bearing is really around the use of this biologic selective lymphodepleting agent. The second question around what’s really unique about the Notch. I think, there are many different aspects as I’ve said. We always think about in any partnership people behind the partners, and Notch Therapeutics as I’ve said, we believe in the scientific founders who really create this field iPSC differentiation into the T cells. Along with that, as I’ve said their platform, ETN platform provides serum-free, cell-free and a synthetic method of differentiating iPSCs to the T cells. And I think, this is where the real – the attraction of the Notch collaboration wise being able to differentiate iPSCs into T cells in a scalable way. And you guys really eyeing towards a manufacturing goals in sufficient quantity and quality from that clinical studies and hopefully at some day, we’re looking towards commercializing iPSC-derived cell therapies.

And, Mark, this is Eric. On the IP side, as you can appreciate, we are not going to be discussing patent matters, but we have the strong legal team here who’s performed much due diligence on this bench.

Thank you. [Operator Instructions] Our next question comes from Raju Prasad with William Blair. Your line is now open.

Thanks for taking the question, and congrats on the progress. I guess, maybe just a follow-up on preconditioning. Can you just provide a little bit of color on – maybe how you’re thinking about which assays you’re putting kind of higher in the hierarchy when making the decisions? Is it more of a reactivity based or engrafting based? And then, when you’re thinking about changing the regimens would it be more along the lines of reducing Flu/Cy before you touched 647, I’m just trying to get a sense of how you’re thinking about changing the regimens if you do and what will guide that? Thanks.

Okay, Raj, thanks for the question. Seems like a lot of questions about the protocol amendment that we are making. As I’ve said, the protocol amendment, this is something that we have internally been discussing from sometime. And in fact, we have indicated in previous communications that we will be making some adjustment to the protocol to test different hypothesis. So this is really driven from that and not necessarily based on the clinical data that we have seen. And we’re going to stay relatively silent about clinical data that’s coming out of the ALLO-501 study. But I would say that to one of your questions, our main focus of adjusting the lymphodepletion is really centered-around maximizing the potential benefit of ALLO-647. As you know, this is our proprietary lymphodepletion agent. It is unique and differentiated from what’s out there. And the fact that we can provide a selective lymphodepletion, we believe that this is potentially significant differentiating factor in our strategy. So obviously, we want to maximize that aspect of ALLO-647, and then underlies about the actions and different things that we plan to test in the ongoing ALPHA study.

Thank you. Our next question comes from John Newman with Canaccord. Your line is now open.

Hey, good morning, guys. Thanks for taking my question. Just curious – sorry to ask another question about the amendment. But just curious, if you would be instituting the changes regarding lymphodepletion going forward or if you will be having some additional patients to the study in order to maintain the current protocol and we are doing things as well as investigate some potential changes to see how those turn out? Thank you.

So this is Rafael. And I’m not entirely sure I understood the point that if, I think, you are asking whether we are going to continue enrolling with making this changes or investigative this changes in 647, perhaps, in earlier cohort. I don’t want to go into all the details of how we’re going to do this. But essentially, I mean, just to reiterate what David said, I mean, this is going to Phase 1 study. The first thing that was – it was designed for – to design – to the studies for dosing. And the choice of ALLO-647 was actually the lowest possible dose that you may know that different doses of the anonymous product, which is [ganpast and trada] So it’s only fitting that in a Phase 2 study before you are going to launch of Phase 2 study you want to optimize both dosing and lymphodepletion both for the maximum benefit and the least amount of toxicity. So in order to do that, obviously, we needed to about some patients treated. And the study has accrued as planned and we found this was the time to make the amendment it’s not something that was in on plan. And it will be evolving out, and we don’t anticipate going back to very early doses when it rolls out. So I think that’s hopefully answers your question, and if it doesn’t just please ask me to clarify.

Thank you. Our next question comes from Michael Schmidt with Guggenheim Securities. Your line is now open.

Hey, this is Kelsey on for Michael. Thanks for taking our question. There is obviously been kind of a high bar set by anti-BCMA frontrunners and you’ve seen 2 anti-BCMA clinical stage as it’s now suspended due to the competitive market. I guess, what do you think the bar is for 715 and maybe does this bar differ between auto versus AlloCAR T approaches given kind of the advantages and disadvantages? Thank you.

Kelsey, thanks for the question. This is David, and I’ll answer that. I mean, we feel based on what we know from the scientific preclinical experiments and how we proceed the AlloCAR T should be working in the clinics. Our baseline assumption is that allogeneic approach should provide about the same level of safety and efficacy at autologous CAR T. I mean, so that is based on – in a number – on a treated basis. So from that perspective that’s our baseline expectation. I mean, obviously, we will have to see in the clinical study. I mean, there are certain things that could leave to a better efficacy we haven’t really backward that into our baseline assumption. I would, however, add that one of the limitations of current autologous therapy is patients who cannot wait to receive the CAR T therapy. If you go back and review the restoration of studies in the CD19 in the CAR T space – autologous CAR T space that left to the approval of Kymriah and Yescarta. 10% to 30% of the patients who enrolled in the clinical studies unable to receive the cells, because they simply cannot wait still the cell that being manufactured. And obviously, as we go into the allogeneic, our model basically would say that the cells can be really be made available to the patients once the depletion is made to treat the patients with the CAR T and I think that could potentially led – lead to more patients are being treated. And if we look at the data based on intense to treat, I think, there are several potential improvement in the efficacy simply from the logistical aspect if the allogeneic CAR T cells have to provide.

Thank you. Our next question comes from Ben Burnett with Stifel. Your line is now open. Ben, if your line is muted, please un-mute.

Thank you. Apologies. Good morning and congrats on the progress. I also had a question on the competitive landscape. So there is a CD19 program from Precision BioSciences, and they have messaged that they could have data potentially within the window that you’ve talked about releasing ALLO-501 data? And I guess, I wanted to ask, can you talk to some of the more technological details that differentiates ALLO-501 from Precision BioSciences CD19 CAR T candidate? Thanks so much.

Yeah. So we are aware of Precision BioSciences, and what they’re doing and what they have said. And I think this is good for the field, I mean, obviously we have seen a tremendous growth in the allogeneic field over the last year and year-and-a-half, since we created Allogene. And I think this is really having lesser interest of the clinicians. And the field is in advancing the cell therapy pharmacologist to the allogeneic. As you know, there are some several differences in how different companies are making out there allogeneic approach. And I think this is – at the end, this is going to accelerate the creation of allogeneic cell feels as we learn from each other and from different approaches that we are taking. We remain very confident in the approach that we are taking. And as we have said, our approaches based on the UCART19, which has treated number of patients in the ALL setting. And when I review the data the genetic engineering that controls the Graft-vs-Host Disease and also allows the cell expansion and provide the early efficacy in the UCART19 studies, I mean, these are the key things that are essential make sure that the approach is viable. And I think that is one of the strengths that we are taking forward as we advance ALLO-501 and ALLO-715 program.

Thank you. Our next question comes from Tony Butler with ROTH Capital Partners. Your line is now open.

Thanks very much. First of all, I actually applaud the amendment. So the first question really – it goes through the differences between UNIVERSAL and ALPHA, and what learnings you may be able to capture as you vary – 645 with Flu/Cy. Do you think it would be reasonable to assume that with each different patient population it becomes an entirely new experiment with the combination, if you will? And if I may just a follow-up on Notch, applause for that deal, but do you actually, are you convinced that iPSC derived T cells are actually not T cell imposters, but in fact can be sufficiently educated in order to behave like normal human T cells, that is to kill appropriate tumors. Thanks very much.

Okay. So, Tony, thanks for that question, especially, I’m going to take the second question and I’m going to defer to Rafael for the first question. So on the iPSC, the question that you’re asking to me is one of the most important questions. Can you generate functioning T cells? And one of the unique advantages of the cell-based therapies, especially the ones that’s using the T cells is the T cells’ ability upon recognition of the target to expand, and with an increased number, that’s where the real efficacy, the depth of the response that we get with the CAR T, I think that is what I believe in. And as I said, the ETN platform, which is propriety to Notch that we have exclusive license for the indications that we are going after, they have shown that using that platform, they can generate functioning T cells. And you may think, well, that everybody can do that. That’s not true. I mean, this is one of the areas that is really not fully answered in the iPSC, whether you can generate functioning T cells. So when we were doing due diligence and having the discussions with the founders of Notch Therapeutics, and when they show this data, I mean, that was really like aha moment, besides their track record, the fact that they had a proprietary reagent. And that is really, it might be amenable for large-scale manufacturing. And also, the data that shows that they can differentiate iPSCs to the functioning T cells. And that really what drove us to jump into this research collaboration.

Thank you.

Yeah, hi, Tony. This is to your first question about the similarities and differences between UNIVERSAL and the ALPHA study. Right, so what I would say is that, as you know, the UNIVERSAL study, A, is earlier, and so, we have the data that we have for ALPHA naturally; and B, it’s a different disease. And so, obviously, to maximize benefit/risk, you have designed already with the idea of trying to get the optimal lymphodepletion and anti-CD52 to try to reduce alloreactivity with the minimal potential toxicity. The ALPHA studies further alone, and as David and I mentioned before, as we move with doses, it’s now time to look at the lymphodepletion again with the same objective. And I think to the point that you were making, it is possible that the different studies for the Phase 2 of lymphodepleting condition in regimen may be different, because of the different diseases. And that’s really what we want to do, is to march along very carefully during the Phase 1 sort of phase of these two trials, so that when we start the Phase 2 study, we have the maximum potential to derive the greatest benefit/risk. So as we see more patients and we see what happens in the ALPHA study, we may also make modifications to UNIVERSAL. But that feels speculative. And time will tell and we’ll update you in the future.

Yeah, Tony, by the way, this is David again. Thanks for recognizing that protocol amendment is something that is really warranted here. I mean, I am somewhat surprised with the number of questions on the protocol amendment, that having been in this field and having been involved in so many different Phase 1 studies, I mean, every Phase 1 studies that I have been involved in will have anywhere between 5 to 10 amendments through the course of the Phase 1. So I know that all of you have a lot of questions about why we’re doing the protocol amendment. But I see it as more in par and as a routine that one has to do as a part of the Phase 1 study.

Thank you. That concludes today’s question-and-answer session. I would now like to turn the call back over to management for any additional comments.

Well, thank you for joining us on the call today. And thank you for your ongoing support of Allogene as we progress our clinical programs. We look forward to seeing many of you at ASH and other conferences as we close out 2019. Operator, you may now disconnect.

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