Allogene Therapeutics, Inc. (ALLO) Q2 2020 Earnings Report, Transcript and Summary

Good morning, ladies and gentlemen. Thank you for standing by, and welcome to Allogene Therapeutics Second Quarter 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 call over to Christine Cassiano, Chief Communications Officer. Ms. Cassiano, please go ahead.

Thank you, operator, and good morning. Before market opened today, Allogene issued a press release that provides a corporate update and financial results for the second quarter ended June 30, 2020. This press release is 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. Rafael Amado, Executive Vice President of Research and Development and Chief Medical Officer; and Dr. Eric Schmidt, Chief Financial Officer. We continue to conduct calls from different locations. So we appreciate your patience should we have any technical difficulties. During today's call, we will be making certain forward-looking statements. These may include statements regarding the success and timing of our ongoing and planned clinical trials, data presentations, regulatory filings, future research and development efforts, manufacturing capabilities and 2020 financial guidance, among other things. These forward-looking statements are based on current information, assumptions and expectations that are subject to change. These statements may involve risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements. These and other risks are described in our periodic filings made with the Securities and Exchange Commission, including our Form 10-Q for the quarter ended June 30, 2020. You are cautioned not to place undue reliance on these forward-looking statements, and Allogene disclaims any obligation to update these statements. I'll now turn the call over to Dr. David Chang.

Thank you, Christine. Good morning, and thank you for joining us on our second quarter conference call. The last few months have been very exciting for Allogene as we unveil the first clinical data from our AlloCAR T portfolio at ASCO. We were very pleased with the initial data from the ongoing ALPHA trial with ALLO-501 and what it means for our allogeneic platform as it paves the way for the development of ALLO-501A, which we expect to enter into a potential pivotal Phase II trial in 2021. Key findings from our initial Phase I data presentation include that ALLO-501 with ALLO-647 as a part of the lymphodepletion regimen was well tolerated with no dose-limiting toxicities, graft-versus-host disease or Immune Effector Cell-Associated Neurotoxicity Syndrome in heavily pretreated patients with advanced non-Hodgkin's lymphoma. We continue to believe that our anti-CD52 antibody, ALLO-647, will be one of the important components in our ability to achieve the promise of AlloCAR T therapies. Initial data from the ALPHA trial supports our strategy with a higher dose of ALLO-647 being associated with a higher complete response rate. Of the eight patients who received a higher dose of ALLO-647 of 90-milligram, five or 63% had a partial response and four or 50% achieved a complete remission. While we await the additional follow-up on patients to assess the durability of response, especially those who are lymphodepleted with 90-milligram dose of ALLO-647, it is worth noting a couple of the important learnings that came out of the initial review of the Phase I data beyond what might be expected from a dose-escalation study. I believe I can speak for Rafael in this as well, in that, as oncologists, it is critical to identify and understand the type of patients that have the potential to respond to a therapy and which do not. In the ALPHA data presented at ASCO, we observed a meaningful anti-tumor activity across multiple tumor histologists and patient baseline characteristics, the one exception being patients who are refractory to previous autologous CAR-T therapy. Initial data from ALPHA suggests such patients may have intrinsic resistance to CAR-T and we are keen to explore the science underpinning this resistance. Across all doses of ALLO-501 and ALLO-647, the overall and complete response rate in CAR-T-naive patients was 75% and 44%, respectively. Although follow-up was limited, these efficacy data are comparable to those reported from autologous CAR-T trial. Lastly, this initial readout gave us a small peek at what may be one of the most exciting benefits of allogeneic cell therapy, on-demand treatment and the ability to redose patients. Overall, the time from enrollment to start of treatment average is five days. Early experience with redosing has been very encouraging. One case study we presented was a 62-year-old male patient with stage 3 follicular lymphoma, who had been refractory to three prior lines of therapy. His first AlloCAR T treatment was with 120 million cells of ALLO-501 and a 39-milligram dose of ALLO-647. He achieved a partial response at month 1, but progressed at month 2. Shortly after progression, he was retreated with another 120 million cells of ALLO-501, and this time, with the 90-milligram dose of ALLO-647. This retreatment led to a deeper response and the patient achieved a complete remission, which was ongoing as of the data cutoff. While there is still much to be done in terms of understanding the potential for redosing, we, along with our clinical investigators and scientific advisory board are very excited to continue this exploration to optimize treatment outcome. We believe we are in an enviable position with the ability to utilize ALLO-501 ALPHA trial to inform our ongoing studies as we proceed in parallel with our ALLO-501A ALPHA2 trial. From an efficiency standpoint, this is a great benefit as we plan for a potential pivotal Phase II trial of ALLO-501A in 2021. You will recall that ALLO-501A is our anti-CD19 AlloCAR T construct in which the rituximab recognition domain have been removed in order to allow a broader population of patients to receive therapy. We are pleased to report that we are successfully advancing our abbreviated dose escalation of ALPHA2. We have completed a cell dose level 1 cohort with lymphodepletion using the 90-milligram dose of ALLO-647 in combination with cyclophosphamide and fludarabine and are now dosing patients in the higher cell dose cohort. Rafael will provide more details on the design of ALPHA2 trial. Enrollment has also continued in the universal trial of ALLO-715 targeting BCMA. The strategy and trial design of UNIVERSAL is in many ways similar to what we have done with ALLO-501. We have recently completed the initial dose-escalation portion of UNIVERSAL which evaluated three different cell doses of ALLO-715. The study is continuing to involve patients to evaluate additional doses, different lymphodepletion regimens, including those that utilize a higher dose of ALLO-647 and treatment expansions. Our plan remains to present initial data from the UNIVERSAL trial in relapsed/refractory multiple myeloma in fourth quarter at a medical meeting. Lastly, as we review the progress we have made across our AlloCAR T platform, we are increasingly enthusiastic about the potential for ALLO-316, our anti-CD70 candidate and breaking down the various to solid tumors. CD70 expression can be found in solid tumors such as lung cancer, glioblastoma and renal cell carcinoma as well as hematologic malignancies, and with adequate preclinical safety, which makes this an exceptional target. RCC, in particular, is known for being responsive to immune-mediated treatment. Hence, we believe it could potentially be responsive to CAR-T therapy. Patients with localized renal cell cancer undergo nephrectomy. However, 30% to 40% of the patients developed metastasis with a 5-year median survival rate less than 15% to 20%. While there has been industry progress in treating patients with metastatic renal cell carcinoma with a VEGF pathway targeting therapies and checkpoint inhibitors, many patients have come to this treatment-resistant disease. Based on our excitement for this program, we have rapidly progressed ALLO-316, and we'll be filing an IND in renal cell carcinoma by the end of this year with a plan to initiate clinical trial in 2021. Operationally, we continue to manage our activities in the face of a challenging external environment. Work from home has become a norm for most of our employees. We have also grouped our teams at Allogene, so those who need to be on-site for lab work had ample space to do so. This has allowed us to continue to advance all of our key clinical and preclinical programs, and I would like to thank our employees for their dedication and engagement during these difficult times. We believe we are moving closer to our goal to have allogeneic cell therapy follow the success of autologous CAR-T therapy, while providing major benefits in time, convenience, reliability, scale and breadth of malignancies that can be targeted. Our efforts to validate aspects of our AlloCAR T platform sets the stage for our ability to advance multiple AlloCAR T candidates in the near term to midterm. Longer term, the progress of autologous anti-CD19 CAR-T therapies are making beyond relapsed and refractory patients, including a recent approval in mantle cell lymphoma served to forge the path for how we might quickly expand indications for our AlloCAR T therapy, including ALLO-501A. As we look to transform the field of cell therapy, our research team continued their work to identify and progress next-generation tools and technologies. And we expect these efforts to keep us at the forefront of innovation as this important therapeutic modality has the potential to serve many patients in need. I will now turn the call over to Rafael for further updates on our research and development activities.

Thank you, David, and I hope you are all staying safe. I'm extremely pleased to report that the initial data from our Phase I ALPHA trial from ALLO-501 presented in an oral session at the virtual ASCO meeting in May exceeded our expectations. Responses were observed across all cell doses and tumor histologies, diffuse large B-cell lymphoma and follicular lymphoma, with an overall response rate of 63% and a complete response rate of 37%. With a median follow-up of 3.8 months, nine of the 12 responding patients or 75% remained in response until the data cutoff. Included in their overall efficacy analysis are 3 patients who were refractory to prior autologous CAR-T therapy. The best response for these patients was disease progression within 3 months. None of these patients responded to AlloCAR T therapy. In CAR-T naive patients, the ORR was 75% and the CR rate was 44%. As David noted, a higher dose ALLO-647 was associated with a higher complete response rate of 50%, deeper lymphodepletion and delayed host T cell recovery, while sparing neutrophils and platelets. One of the ongoing responders was a patient with an initial PR who progressed by month two. This was a patient that David referred to earlier, who achieved a complete response after retreatment with the same dose of ALLO-501, a 90-milligram dose of ALLO-647. I would like now to put this data into context. Firstly, the enrolled population was heavily pretreated. The median number of regimens was poor. 95% have stage 3 or stage 4 disease, and 86% of the 22 patients were refractory to the last regimen as defined by progression within 12 months of therapy. We treated a mix of follicular lymphoma and diffuse large B-cell lymphoma patients. This was done to collect as much information as possible in this Phase I study. We were able to gain clear signals of activity in both patients subsets. You may recall from our ASCO investor meeting that we juxtaposed our initial data from the CAR-T naive patients in the ALPHA study with the results published from a range of autologous CAR-T studies. The point of that analysis was not to make direct comparisons that this study's varying composition, size, Phase II development, enrollment criteria and a number of other parameters, but rather to illustrate what may be possible with our CAR-T. The results of this analysis showed clear similarities between autologous and AlloCAR-T in response rates at this early time point. While these promising initial findings will need to be confirmed with more patient experience and longer follow-up times, we believe we have answered yes to several important questions that the ALPHA trial aimed to address, namely, ALLO-501 can be successfully manufactured; ALLO-501 can be safely administered without causing clinically relevant graft-versus-host disease; ALLO-647 can be safely administered and it leads to dose-dependent lymphodepletion that associates with ALLO-501 expansion; and ALLO-501 can provide complete responses across multiple histologies. Beyond these questions, we've also gained important understanding as to which patients may not respond to Allo CAR-T therapy, how we may be able to improve patient outcomes with redosing, which continues in the current protocol and how to optimize lymphodepletion. In addition, the promising safety profile demonstrated by ALLO-501 and ALLO-647 opened up the potential to explore dosing in the outpatient setting. Overall, these findings enhance our enthusiasm for what may ultimately be possible with the AlloCAR-T therapy platform. We look forward to our next data readout from the ALPHA trial, which we expect to be in late 2020 or early 2021. Meanwhile, our Phase I/II ALPHA2 study is actively enrolling patients. ALPHA2 is a single-arm, open-label multicenter study of ALLO-501A in non-HLA-matched adult patients with relapsed/refractory large B-cell lymphoma. Patients with follicular lymphoma are excluded. Patients must have received at least two prior lines of therapy, including an anthracycline and an anti-CD20 monoclonal antibody. While prior autologous CAR-T therapy is ALLO, if the tumor remains CD19-positive in patients who previously responded to autologous CD19 CAR-T therapy, we are considering whether to enroll autologous CAR-T patients as we learn more from the ALPHA trial experience about the outcome of patients who had a meaningful response to autologous treatment. The primary objective of Phase 1 is to evaluate the safety and tolerability of escalating doses of ALLO-501A in combination with ALLO-647, cyclophosphamide and fludarabine. Key secondary objectives include ALLO-501A cell kinetics, ALLO-647 pharmacokinetics and depth and duration of host lymphocyte depletion. The study will replicate certain aspects of the ALPHA study to corroborate the findings from that trial. We initiated dosing with ALLO-501A at 40 million Allo CAR-T positive cells, a dose cohort that was abbreviated to a single patient. The trial will follow a 3-plus-3 design with patients enrolling a dose level two cohort of 120 million cells, and a dose level cohort of 360 million Allo CAR-T cells. We're using a total dose of 90 milligrams of ALLO-647 administered concomitantly with flu/cy. We continue to target moving into the Phase II portion of this study in 2021. Our additional clinical focus is our Anti-BCMA Allo CAR-T cell therapy for the treatment of relapsed/refractory multiple myeloma. We have a 3-pronged clinical strategy targeting BCMA. UNIVERSAL, our Phase I trial with ALLO-715 is well underway, and we are on track to report initial data from this trial in the fourth quarter of this year. This study was initially designed to explore optimal dosing of all the components of the lymphodepletion regimen, including ALLO-647, fludarabine and cyclophosphamide with patients receiving ALLO-715 at 1 of 3 doses: 40 million, 160 million and 320 million cells in a 3-plus-3 dose-escalation design. As David noted, we have recently completed the initial dose-escalation portion of the UNIVERSAL trial using 39 milligrams of ALLO-647 and enrolling in other lymphodepletion cohorts, which admit fludarabine. The endpoints being assessed are safety, tolerability, death and duration of lymphodepletion, cell expansion and antitumor activity, including minimal residual disease rate. Given the complexities of this disease and propensity for disease progression for patients with multiple myeloma, we are excited to explore regimens, which include both lower and higher doses of ALLO-647. We also look forward to applying all the lessons learned across our platforms, such as redosing as we evaluate ways to optimize therapy for this patient population in need of novel treatment. The other two prongs of our BCMA strategy include exploring the use of a gamma secretase inhibitor in combination with ALLO-715 and investigating our Turbo CAR-T echnology platform to potentially enhance the efficacy of an anti-BCMA CAR-T therapy in myeloma. Since our last earnings call, we have advanced a regulatory discussion on how to best evaluate the combination of ALLO-715 with the gamma secretase inhibitor, nirogacestat, from our partners at SpringWorks Therapeutics. We expect to file an IND to support the clinical evaluation of this combination this year. The innovation behind TurboCAR could be a breakthrough as this technology has the potential to expand Allo CAR-T cell viability and efficacy while reducing CAR-T cell dose requirement and overcoming exhaustion. These properties may enable CAR-T therapies in harder to treat hematologic malignancies and solid tumors. ALLO-605 will be our first TurboCAR clinical candidate. We are excited about what this technology may mean for next-generation AlloCAR-T therapy in multiple myeloma and anticipate submitting an IND for ALLO-605 in 2021. At the American Society of Gene and Cell Therapy Annual Meeting in May, we presented preclinical findings on our Turbo CAR-T echnology. The versatility of this technology could allow us to harness the signaling of different cytokines. And we believe TurboCAR could eventually become a standard for Allo CAR-T platform. As our clinical teams focus on clinical trial progression for ALLO-501, ALLO-501A and ALLO-715, our research teams continue to progress our preclinical activities. Our preclinical work on ALLO-316, our anti-CD70 candidate, continues as we look to traverse the use of cell therapy from hematologic malignancies into solid tumors. Our ALLO-316 IND is planned by the end of this year in treatment-resistant renal cell carcinoma with the potential to study other malignancies in the future. In addition to the above, preclinical work continues on candidates, such as ALLO-819, an investigational AlloCAR-T therapy targeting Flt3 as a novel treatment for acute myelogenous leukemia as well as earlier stage technologies, such as our induced pluripotent stem cell program. We are relentless in our pursuit to bring Allo CAR-T therapy to patients and are very excited by the strong momentum we've achieved across both our clinical and preclinical pipeline. I look forward to continuing to provide updates at scientific congresses. While we continue to leverage our internal capabilities and our existing partners, we will also pursue innovation externally as we advance additional pipeline candidates and next-generation technology. I'd like to now turn the call over to Eric to review financials.

Thank you, Rafael, and good morning. Let me start by thanking all of you on the call or those who may listen in later to the replay, for your ongoing support of Allogene in our efforts to bring Allo CAR-T therapy to patients. That support was particularly evident during our recent financing, which benefited from the participation of many new and existing shareholders. In June, we closed a follow-on offering that raised $632.5 million in gross proceeds prior to deducting underwriting discounts, commissions and offering expenses payable by us. Included in this figure is the exercise in full by the underwriters of their option to purchase additional shares of common stock. As a result and as noted in our SEC filings and second quarter press release issued earlier today, our financial position is stronger than ever, with cash, cash equivalents and investments totaling $1.1 billion as of June 30, 2020. In the second quarter, our research and development expenses were $47.3 million, which included $8 million of noncash stock-based compensation expense. General and administrative expenses were $15.9 million for the second quarter of 2020, which includes $8.8 million of noncash stock-based compensation expense. Our net loss for the second quarter of 2020 was $61 million or $0.53 per share including noncash stock-based compensation expense of $16.8 million. I am pleased to report that our build-out for our Newark manufacturing facility is continuing in full force. Thus far, we have experienced only minor delays as a result of the pandemic, and we remain on track to bring the manufacturing facility online in 2021. We maintain an expectation that our full year 2020 net losses will be between $260 million and $280 million, which includes an estimated non-cash stock-based compensation expense of $70 million to $75 million and excludes any impact from potential business development activities. With that, we will now open the call for your questions.

Thank you. [Operator Instructions] Our first question comes from Phil Nadeau with Cowen and Company. Your line is now open.

Good morning and thanks for taking my question. Abiding by the one-question rule, I was wondering if you could give us a bit more detail on what we should expect from the Q4 data release from the UNIVERSAL trial? Are we likely to just see results from that initial dose escalation portion with the 39-milligram of ALLO-647? Or is it possible that we could get data from the additional cohorts?

So Phil, first of all, good morning, and I hope for those who are in the east coast weathering the storm well. I hear that it has passed and things are getting better. The question that you're asking about what to expect for the 715 data presentation at the year-end, I'm going to refer to the part 2, Rafael to answer the details. Rafael?

We have, as David mentioned and I mentioned in the initial remarks, finished the dose escalation, so that was at 3 plus 3. We didn't have any DLT. We also put some patients, as I mentioned in my remarks, in the CA cohort as well. And we will treat some patients at 90 milligrams. The total number of patients that will make it into the end of the year presentation is still to be determined, but I think you can probably get an idea of how many patients, if you compare what we presented at ASCO so there would be a number thereabouts similarly to that.

And maybe just one follow-up. Can you give us an idea of the – actually, the duration of follow-up for the patients that will be in that initial data release?

You have to calculate what the median follow-up will be, but I think it's difficult to know. Obviously, the patients who have started at 40 million will have a much longer follow-up than the patients that started at the later doses. But that's a number that I think we will come up with once we do the analysis. We don't have that number right now.

Great. Thanks for taking my question and congratulations on all progress.

Thank you.

Thank you. [Operator Instructions] Our next question comes from Salveen Richter with Goldman Sachs. Your line is now open.

Hi, everyone. Thanks for taking the question. This is Andrea on for Salveen. David, maybe just some thoughts on where do you stand with optimizing the lymphodepletion for the 501 trial? And what still needs to be done here?

In terms of optimizing lymphodepletion, I mean, we already saw very encouraging data as we increased the dose of ALLO-647 from 39 to 90 milligrams. And obviously, at the ASCO presentation, the follow-up was short, so we are waiting for the longer-term follow-up. So while that's ongoing, we are also doing few additional testing because at the end, we have this quite unique situation of heading two different studies ongoing, and we have a great opportunity to really trying to see what the allogeneic cell therapy can ultimately do. And that's just getting to why autologous cell therapy can do but perhaps we can do more. So we are continuing to optimize a little bit more. But right now, the main focus is on the follow-up of the patients who are treated with the 90 milligrams of ALLO-647 where we saw higher rate of complete remission.

Thanks so much.

Thank you. Our next question comes from Biren Amin with Jefferies. Your line is now open.

Hi, guys. Thanks for taking my question. So I think you said that the next update from ALPHA may come at the end of the year, but there's also a window for data reporting out in early 2021. So just trying to understand, what are the factors that are driving the timing for the ALPHA update?

So I'm going to ask Eric to respond to that question. Eric?

Yes, thanks, David. Biren, it's Eric. As was the case with our initial ASCO data set, we really want to be sure that an updated presentation is meaningful and informative. As you know, it's just been a couple of months since the ASCO presentation. So we'll continue to move the ALPHA study forward, follow patients, enroll additional patients. And at the same time, we'll look for a scientific form that provides an opportunity to showcase that meaningful update. As you mentioned – or as Rafael really mentioned in his script, that could be either late this year or early next, but we just haven't – we haven't decided our plans quite yet.

Okay, great. Thanks for taking my question.

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

Hi, good morning. This is Gavin on for Cory. So I acknowledge this might be a bit premature, but just interested in your thoughts, nonetheless. Given the scrutiny on CMC with respect to gene and cell therapies, as evidenced from some of the other CAR-T – auto CAR-T players, what steps can you take today are in early clinical development to mitigate some of the potential speed bumps down the road?

So let me take that question. I mean, CMC is an area that we are paying a lot of attention. We certainly did that when we are involved in the development of autologous CAR-T therapy and we are carrying that through as we enter into the allogeneic, where the cell manufacturing is, I would say, a little bit more complicated. And we really break this down into how to develop the proper analytic assay so that we can continue to improve the manufacturing and certainly taking care of all the assays that are necessary to qualify the release material according to the regulation. And it includes both what we consider as a release test as well as additional explorer test that's necessary. So that's just one part of the equation. And the other part is the things that are needed to ensure the manufacturing facility can pass any kind of preinspection which we expect. That sounds a little bit premature when we are still building out manufacturing facilities in Newark, but already, our teams are thinking ahead in preparation of the BLA filing. So to that extent, I can answer that much. I mean, but I can tell you with the experience that we have, we are looking into every possibilities to make sure that we can address any kind of regulatory questions that may come up.

Great. Thanks for the color.

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

Hi, guys. Good morning and congratulations on the progress during the quarter. Just wanted to get your updated thoughts on durability of response with the ALPHA trial and kind of what we saw at ASCO. And as we think out durability response for the future, clearly, the overall response rates and the CR response rate was great. And you had nine out 12 patients responding with a median of 3.8 months. And the KOLs to say that in non-Hodgkin's, to get that 40% to 50% relapse-free rates out one to two years, that most of those patients are relapse-free at three months. So if you look at those responders, I guess, about eight of them made it three months and five out of eight are still responding, which is 63% relative to kind of that 40% to 50% that we've historically seen, and that's at the 39 mg, 647 dose, before you even see more data than 90 mg dose. So I guess, would you guys agree with those comments that the KOL made is 3 months time point as we think about durability response, particularly important when we look at kind of longer-term relapse-free rates?

Tyler, thanks for the question. And certainly, we are following the durability data coming from the autologous and continue to be encouraged by what they are seeing, especially year two and year three. As you point out, I mean, there is a good correlation between the durability at month 3. I mean I would say, first six months and the longer-term durability. And in our study, we haven't really gotten to that point of six month plus, but certainly, we are very encouraged with the high rate of complete remission than what we are seeing as well as people who continue to be in response at the time of data cuts. So durability is very important. And we will see how the durability holds out, especially as we go up to the 90-milligram where the data because of the cutoff, where to follow, it was relatively short. But we are highly encouraged by what we saw at ASCO data presentation, and we look forward to updating you in near future.

Great. Thanks for taking the question.

Thank you. Our next question from Debjit Chattopadhyay with H.C. Wainwright. Your line is now open.

Hi, guys. Good morning. Thanks for taking the call. This is Aaron on for Debjit. So I wanted to ask a question about redosing patients that have been previously treated only with Allo CAR-T s. What kind of – do you need to see relapse for you redose? Or is there other biomarker or clinical points that you are looking for prior to redosing? And how do you settle that?

Great question. I'm going to ask Rafael to address your question.

Yes. So I think this is an area that's really ready for innovation because in addition to the classical being in response of 3 months, predicting long-term responses, there are now molecular assets that can be much more accurate in terms of predicting what patients will remain in response and which patients won't. So at the moment, if redosing is allowed in all our protocols, and we are redosing patients that respond and progress, and we have that example that we talked about in the prepared remarks and we continue to do that. I think what is really exciting is the fact that while we are doing the dose escalation for 501A, we're still being able to experiment in 501, with things like redosing. And so redosing is now being tested in 501A in a broader number of patients to really see whether or not we can improve upon the autologous results, which, although they are fantastic, there's still a lot of room for improvement. So you should see redosing in other patient populations in the future.

Okay. We may see data on this at year-end or early 2021, the redosing?

We'll update you with any additional data we collect, whether it's year-end or early next year. And just one other aspect, right now in the ongoing studies, the redosing is a reactive redosing, meaning that patient, when they progress or when they do not achieve a – what we consider as a good response, we give the patient opportunity to receive the redosing. And certainly, that's an area, as Rafael had mentioned, that we are quite interested in. It's a great opportunity for the allogeneic cell therapy, given the availability of the cell products that can be provided to the clinical site.

Okay, thanks, Dave. Thank you guys.

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

Hi, good morning guys and thanks for taking my question. Just wondering with a new CD19 antibody entering the NHL treatment [Technical Difficulty] can you make any general comments on the performance of CD19 CAR-Ts either auto or ALLO in patients who have had prior trastuzumab? Are there any precedents for that?

Mark, thank you very much for that question. I'm going to ask Rafael to provide the response. Certainly, we are very excited about new therapy continuing to become available for patients with non-Hodgkin's lymphoma.

Yes. I echo those comments. I mean, I think it's fantastic that there's a new product. And I think also the development of that product was, I think, exemplary in the way that they obtain a label in patients with stem cell in eligible population. But as we said, history medicine therapies are also in sequence and they are combined. And we expect that both types of therapies, both autologous and bispecifics and others that may be coming will coexist. Antibodies may need to be given constantly versus, as you know, cell therapy, which may be a onetime treatment, redosing notwithstanding. So I think overall – like, what happened in myeloma, what happened in renal cell carcinoma, countless other tumor types – these therapies, the physicians, investigators will find a way to cycle for the benefit of patients. So we're pretty happy that actually this approval took place.

But no information about patients who received a CD19 CAR-T post-CD19 antibody?

Did that information – I think, it will need to be forthcoming. I don't think there's enough information in the field to really be able to tell. I mean we know that in the BCMA space, patients can't respond to cell therapy as they haven't received BCMA antibodies. And it is possible, depending on the mechanism of resistance to the antibody that they may respond to cell therapy. The mechanisms of resistance are being elucidated nowadays as we speak to both antibodies as well as cell therapy.

Okay, thank you.

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

Hi guys. Thanks for taking the question. My question for both David and Rafael is a bit of a broader question. I wonder, thinking about autologous and allogeneic bone marrow transplant is a good corollary for ALLO-501. I mean, we know the first allogeneic bone marrow transplant was actually done long, long time ago, I think, 1957. Obviously, allogenic BMT has expanded greatly since then. What I'm wondering is, going back to the bone marrow transplant today, do they hold out or wait for an autologous donor? Or do they normally utilize an allogeneic donor? I'm just wondering if this might be a good way to kind of think about this autologous versus allogeneic CAR-T question today. Thanks.

Yes. Rafael, do you want to take that question. John, thanks for the question. Certainly, the landscape in the non-Hodgkin's lymphoma continue to improve as your question and the previous question about the new therapy coming in. So Rafael?

Yes. I'm assuming this is in the context of non-Hodgkin's lymphoma. Allogeneic bone marrow transplant is relatively rare in this space. Autologous stem cell transplant is a lot more common. So in fact, there are many patients in our studies and other studies that have received stem cell autologous therapy prior to entering into the study. The bearing of that with regards to allogeneic versus autologous CAR-T therapy, I think, is very disparate. Because, in general, the benefits of autologous CAR-T therapy are very different from the benefits of – I'm sorry, the benefits of allogeneic CAR-T therapy are very different from the benefits of allogeneic bone marrow transplant, which again is very toxic in these patients. They are mostly elderly patients. And unless it's a haploidentical transplant, it's hardly ever done. So I think that's – I mean, I would limit my comments to those.

Okay, great. Thanks.

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

Hey guys. Good morning and thanks for taking my questions. I just had a follow-up on your comments around patients in the ALPHA study that received prior autologous CAR-T therapies. I think you mentioned none of those responded, and there may even be sort of a – there maybe a CAR-T resistant-type phenotype. And I was wondering how much more work you think you will be doing to better understand that and how this might affect ultimately the development path for ALLO-501A given that auto CAR-Ts may expand in use as additional trials readout for YESCARTA and other products.

Yes. Michael, I'm going to ask Rafael to expand on the response because I think what you are asking, certainly, we have seen in our study to be very interesting findings that are emerging. One thing that I would emphasize – yes, there has been a lot of – well, not a lot, limited reporting of the redosing, as it was done at ASCO in the autologous CAR-T setting. And even in the autologous CAR-T setting, people were reporting that those who relapsed early on tends to respond poorly. In our study, we did something that's very unique, which was enrolling patients who failed, and we define the failure as patients who are not able to maintain response for more than one to two months. So we involved those exceptional patients, and we are finding something that we think is very interesting and potentially could, at some day, lead to more predictive medicine. So with that, Rafael, do you want to expand on that a little bit more?

Yes. I would say that the mechanisms of resistance are being elucidated. There's data from Marco Davila from Moffitt about intrinsic resistance due to defacing the – that receptor pathway, and there are issues with T19 molecule itself, the presence or the mutations in T19. And so there are patients that have intrinsic resistance to oral CAR-T cell therapy, and we wanted to try to see whether they would respond to AlloCAR T therapy, and we found out that the patients that which didn't. That doesn't mean that a patient that benefited from auto CAR-T therapy for a period of time that's long may not benefit from autologous. And so therefore, we haven't yet completely given up on these patients. And we will, I think, get an answer as to whether or not there's a subpopulation of patients that they see autologous CAR T therapy relapse and can benefit from allogeneic CAR-T therapy, and that is something that we're going to study.

Understood. So it sounds like those patients were kind of preselected to be very poor response in the first place, as I understand that.

Right. Those patients – those patients would – we wouldn't treat further because I think the experience is that those patients don't do well.

All right. Thank you.

Thank you. Our next question comes from Reni Benjamin with JMP Securities. Your line is now open.

Good morning guys. Thanks for taking the questions and congratulations on all the progress. My first question has to do with the manufacturing facility. Can you just remind us – I know it will be online in 2021. What kind of bridging or comparability study needs to be done, need to be online prior to a pivotal study or just kind of prior to commercialization? Can you just remind us what the capacity of that facility will be ultimately?

Yes. So great question about bringing a new facility. I mean this is something that industry frequently deals with, doing the kind of bridging study. And in the cell therapy area, we believe that the bridging study will be limited to analytic bridging studies. So I think that already always was in plan, and we are addressing that as we go forward. And as we have mentioned, the Newark facility, which is really a state-of-art facility, is going to come online in 2021 and start manufacturing the CGMP quality clinical material. So everything is proceeding according to plan.

And we said we could commercialize multiple commercial products out of that facility?

Absolutely.

Got it. Got it. And just as a follow-up. Can you just give us a sense as to how Notch collaboration is going? I think in the past, you guys have talked about kind of a focus on alpha-beta T-cells, but I also wanted to get your thoughts if you guys are thinking about other types of cell types, including gamma delta type T-cells as well.

Yes. So I'm going to keep the responses relatively quick since we're running out of time. The Notch collaboration is proceeding extremely well. Certainly, the point you are making about the T-cells, I mean, that's the primary focus. But we also know that cell differentiation technology that the Notch has developed can allow the cells to develop into other lymphocyte phenotype. So that's an open question. And obviously, the IPFC, we're really building for our future, and we'll continue to explore many different options as we expand the collaboration. And so far, we are very pleased with how the collaboration is going.

Great. Thanks for taking the question guys.

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

Thanks for taking the question. I just want to get some clarity on the UNIVERSAL results in the context of the broader multiple myeloma program. Will there be some data on maybe soluble BCMA levels in these patients and responders versus – just in the context of there being a clinical trial with the GSI plus in ALLO-715 in 2021? And then any other context on data that you might get that would guide where TurboCAR might fit in, in these patients, just thinking about potentially having three ongoing clinical trials in multiple myeloma and how you enroll patients? And then just, is redosing in the protocol for UNIVERSAL? And could we see data on any redosed patients in Q4? Thanks.

Okay. I think that's Rafael. There's several questions there. So let's keep the response real quick. Rafael?

So I think in terms of BCMA levels and circulating and also in the subsurface, that's something that we plan to study. Redosing is included in the UNIVERSAL protocol, so we will – we have the ability to do that. And with regards to 605, we are really excited about the innovation that, that brings. And we know preclinically that the results are better, and there's a lot of room for improvement in multiple myeloma. And it's something that's going to cycle very closely with 715 nirogacestat and then 605. So I think we're sort of moving through the innovation steadily. I hope that answers your question.

Yes, that’s helpful. Thanks.

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

Thank you. Hi, good morning guys and thanks for taking the question. I was wondering now that we got to digest data from ASCO from the other CAR-Ts there in multiple myeloma, we saw some – maybe some level of MRD-negative data from the Johnson & Johnson product as well as for others. Can you maybe talk to us about what level of upfront tumor eradication do you think is necessary to have a meaningful impact on disease progression? Do you think you need to go to negative 5% or negative 6%? And then are you planning on presenting this data in Q4?

Yes. So let me just take that question quickly. In terms of – the question is really related to the new way of assessing the tumor response using the molecular basis, they will take the MRD level 5 or MRD level 6. I mean, we are following the emerging data. I mean the deeper response seems to do better. And certainly, as part of the study, we will be evaluating the MRD. In terms of how it relates to the duration of response, I think that's something that we are all watching as the data mature in nirogacestat's CAR-T setting. But I think this is really a new way that one can assess the disease response, and we are very excited that the early read to the durability can be obtained from the MRD assessment. So I hope that answers your question.

Yes, thank you.

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

Hey, thanks very much and morning. Just a question back to manufacturing. As you start to bring ALPHA2 online, are there any learnings from the first ALPHA study in terms of manufacturing? And I guess also in terms of donor type and donor age, anything that's led to any modifications in the manufacturing process in ALPHA2 versus the first ALPHA study?

Ben, great question. I mean, we try to stay relatively silent on all the things that we are doing on the manufacturing. I mean, there is a lot going on in terms of making manufacturing robust, which we have already done but also trying to characterize the donor types. That's something that will require more data points, but it's something that we are very interested in learning. So far, we have been able to manufacture the cell products consistently for not only 501 and 501A but also for the 715. So I think that gives some sense of our capability in the [indiscernible], but this is something that we will continue to invest and continue to improve, not just in terms of quality of the cells but also the yield which is very important.

Ben, you may also recall that in the initial ASCO presentation, we treated all 23 patients with the same manufacturing run. So in terms of clinical findings, it's premature for us to be able to comment there. Thank you. And I'm showing no further questions in the queue at this time. I'd like to turn the call back to the speakers for any closing remarks.

First of all, thank you for joining us on the call today and your support for Allogene as we continue to progress our pipeline on AlloCAR T therapy. So hope you all stay well and healthy. And with that, operator, you may now disconnect.

Thank you. Ladies and gentlemen, thank you for your participation on today's conference. This does conclude your program, and you may now disconnect.