Allogene Therapeutics, Inc.

Hello, thank you for standing by, and welcome to Allogene Therapeutics' second quarter 2021 conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone. 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 to all on the line, welcome. We will continue to limit questions to one per person so we can get to as many as possible during the hour. After the market closed today, Allogene issued a press release that provides a corporate update and financial results for Q2 2021. 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, including the timing and ability to advance our Alpha-Q trial to Phase II, data presentations, regulatory filings, future research and development efforts, manufacturing capabilities, and 2021 financial guidance, among other things. These forward-looking statements are based on current information, assumptions, and expectations that are subject to change. A description of potential risks can be found in our earnings press release and latest SEC disclosure documents. You are cautioned not to place undue reliance on these forward-looking statements, and Allogene disclaims any obligation to update these statements. I'll now turn the call over to David.

Thank you, Christine, and good afternoon. We launched Allogene in the second quarter of 2018 with a bold mission, to create and lead the next revolution in cancer treatment by delivering to patients the first allocardial therapies for blood cancers and cell tumors. Three years later, we have made a giant leap for both Allogene and the field of cell therapy, as data from our lead program bring us one major step closer to realizing our goal of commercializing a first-in-class and best-in-class off-the-shelf cell therapy. As we enter a new stage in our life cycle, our focus turns towards advancing our lead development candidate, Allo501A, into a pivotal phase two trial for relapsed refractory non-Hodgkin's lymphoma by the end of 2021. Following initial data presented at our CD19 forum in May and ASCO in June, we are increasingly confident in the safety and efficacy profile of Allo501A and its path forward. As we shared during the CD19 forum, the alpha trial demonstrated that Allo501 can achieve deep and durable responses in patients with relapsed refractory non-Hodgkin's lymphoma who are CAR-T-naive. with an overall response rate of 75% and CR rate of 50%, and the six-month CR rate of 36% in patients with large B-cell lymphoma histology, which is the patient population of our first pivotal trial. The safety profile was also very encouraging. No dose-limiting toxicities or graft-versus-host disease and limited ICANN and cytokine release syndromes observed. I have been involved in the development of CAR T therapies from the early days, and the available efficacy and safety profile of Allo501 and Allo501A clearly show that all the key principles that we learned from autologous CD19 CAR T therapies are holding true in our allogeneic CAR T therapy. Setting aside the limitations of drawing a cross-trial comparison, what we are seeing in our studies both in the initial responses, durability of responses, and the safety profile from a single infusion of LO501 or LO501A are on par with the data from pivotal trials of FDA-approved autologous CD19 CAR T therapies. Meanwhile, we have exceeded the bar set by the autologous therapies in other respects. our Allocarti therapies can be delivered to patients within days rather than weeks. And patients who enrolled in our studies can be nearly guaranteed to receive our products. In the Alpha trial, 98% of the enrolled patients received Allo501 within a median time of five days from enrollment to start of therapy. By comparison, in trials deploying autologous therapies, up to 30% of patients who have undergone leukoparesis for some manufacturing were unable to receive treatment due to interval disease progression while waiting for the CAR T-cell products, or even worse, due to manufacturing failures. Given the tremendous benefit that Allo501A can bring to patients, we remain highly focused on execution. Top of mind today is our preparation for the industry's first allogeneic pivotal trial. As our planning towards this important milestone progresses, we look forward to providing a clinical update on our CD19 program in the fourth quarter. Shortening the time to treatment and ensuring access for nearly all suitable patients is just the beginning of how we can leverage the attributes of allogeneic CAR-T therapies. As we look down the line to next generation therapies, our aim is potentially enhance the efficacy and safety of our products beyond that of autologous therapies. Our research team is actively working on new strategies to evade premature ejection, enhance cell potency, improve product consistency, and overcome the solid tumor microenvironment. Some of these technologies such as our turbo car key approach, have now advanced into clinical development. Others are progressing nicely behind the scenes. So while the initiation of our first pivotal trial will represent a critically important milestone for Allergen, it represents just the beginning of our new product innovation cycle. We are now also preparing for the potential transition from a clinical stage company to a commercial enterprise. We have begun to build our commercial team, which will focus on product positioning, maximizing adoption, and ensuring access. We have bolstered our internal efforts by expanding our board with the appointment of Liz Barrett and Vicky Saddle as directors. Liz, currently the president and CEO of Urogen and former CEO of Novartis Oncology, is one of the rare executives with deep experience in the commercialization and launch of novel oncology therapies, including in autologous CAR T therapy. Vicky, a former professor in practice of molecular and cell biology at Harvard University and president of Vertex, has an exceptional track record of operational execution at several leading biotechnology companies. Our new board members will be vitally important as we prepare for the potential launch of a first-in-class product. Which brings us to manufacturing. From the beginning of Allergen, we have maintained that having in-house manufacturing capabilities would be key to controlling our ability to deliver off-the-shelf cut-key cell therapies faster, more reliably, and at greater scale to all patients. Later this month, we will host an event to inaugurate our CellForgeOne state-of-the-art manufacturing facility in Newark, California. The facility is intended to house commercial manufacturing, analytical testing, formulation, packaging, and distribution of cell therapies, allowing us to optimize important steps in the cell therapy production process and allow allocardial therapies to be available to patients within days. We are excited to showcase the convergence of scientific excellence and cutting-edge manufacturing at our CellForge-1 facility. The rapid build-out and operationalization of this facility is yet to gain another example of our team's determination to let nothing, including the unforeseen challenges presented by a global pandemic, getting in the way of our goal to bring the first allogeneic CAR T therapy to patients. I thank them for these tireless efforts to bring this facility online in preparation for CGMP manufacturing in the second half of 2021. Positive phase one data from our alpha and alpha two as presented at ASCO and our CD19 forum continue to validate our allogeneic platform. and we are aggressively advancing our pipeline with more confidence than ever before. We currently have five clinical trials underway, two in our CD90 program, as noted, two candidates that target BCMA, including one that incorporates our novel turbo car technology, and one program in solid tumors. Our robust multiple myeloma program is an example of how we've been able to rapidly advance optimize, and deliver meaningful progress across multiple strategic approaches to allogeneic CAR-T. Beyond our ongoing universal trial, we were pleased that our first TurboCAR clinical candidate, Alof605, received US FDA Fast-Track designation for the treatment of patients with relapsed and refractory multiple myeloma. We are excited to announce that we have begun dosing patients in phase one of IGNITE study of allo605. We also have our sights set on confronting solid tumors, where the need is unquestionably high for a new innovation. We remain optimistic for the potential of our Allocarti platform to rise to the challenge. Our initial program targets CD70, and earlier this year, we launched our Traverse trial evaluating allo316 in clear cell renal cell carcinoma. As we continue to treat patients, we plan to share initial data next year. Over the next 6 to 12 months, we expect to have an increasing amount of data across multiple programs that will provide critical insights and inform how we best optimize the promise of our platform. Unwavering execution has already allowed us to generate the largest set of clinical and translational data on allocardial therapies, which we will continue to deploy towards enhancing our product candidates. We are incredibly proud of what we have achieved to date, only made possible by our team's steadfast focus on making allogeneic cardiac therapy a reality for patients. While being an industry leader often entails overcoming tall obstacles, it also provides the privilege of being able to set the pace of innovation, shape important parameters in the field, and define success. At Allogene, we believe we are up to this challenge, and we are grateful for your support as our vision for the future of allogeneic cardiac therapies is continuing to materialize. I will now turn the call over to Rafael for a more in-depth look at our research and development activities. Thank you, David. As you might anticipate, our research and clinical teams have been increasingly focused on advancing our portfolio of allocardial therapies. As David mentioned, we are on track with our plans to initiate a pivotal phase two trial for allo501A in non-Hodgkin's lymphoma. We view the data that we reported in May for the alpha trial, including a 36% complete response rate at six months in large piece of lymphoma, as a sign that we are on the right track and look forward to exploring whether the use of consolidation therapy might lead to even greater promise. Across all non-Hodgkin's lymphoma histology, all of 501 demonstrated an overall response rate of 75% and a CR rate of 50% across histologists and CAR-T naive patients. At the time of the data cutoff, the longest ongoing complete response was at 15 months in both large basal lymphoma and follicular lymphoma. Importantly, given our intent to move Allo501A into our pivotal study, we were also able to demonstrate that Allo501A, which eliminates the rituximab recognition domains in Allo501 to allow for use in a broader patient population, has comparable safety and efficacy to Allo501. As we look to find ways to maximize all levers afforded to us by the nature of our allogeneic platform, one area of distinction for us is our lymphodepletion platform, which supports consolidated dosing. During our CD19 day, we also highlighted the initial data on consolidation therapy, which leverages the unique attributes of the off-the-shelf allogeneic cell therapy and our proprietary lymphodepletion regimen. We are highly encouraged by the results, especially the tolerability of consolidation and observed conversion of initial PR to CR. Pending additional follow-up, we plan to incorporate consolidation into our pivotal study design. Our approach to consolidation dosing is not currently available for autologous therapies or even other allogeneic therapies that traditional lymphodepletion regimens will eliminate previously infused cells. In contrast, Allo647, as the sole lymphodepletion agent for the second dosing, is capable of supplementing the activity of the first dose, allowing for expansion and persistence after the second dose. This is an important advantage and one that we plan to fully investigate in both our CD19 and BCMA portfolios. We are currently finalizing our proposed plan to discuss proceeding to the Phase II trial with the FDA. And in the collection of data and favorable FDA feedback on the design of the trial for the registration of both Allo501A and Allo647, we currently intend to initiate the Phase II portion of the Alpha-2 trial at the end of 2021. I have been fortunate to have been involved in the development and approval of multiple cancer therapeutics and know firsthand how much effort is involved in the preparation towards pivotal trials, including extensive and complex regulatory interactions clinical development, and manufacturing activities. I would like to extend my thanks to the allogene teams who are working tirelessly to lead us to the pioneering activities required for the execution of our first pivotal allogeneic cell therapy trial. Although we're furthest along in our CD19 program, we're committed to advancing allocardia therapies across a broad spectrum of targets in both liquid and solid tumors. We were pleased to have received Regenerative Medicine Advanced Therapy designation granted by the FDA for Allo715 based on early clinical data and the potential to benefit patients with unmet medical needs. The universal trial continues to enroll patients to Allo715, including in combination with Neurogastastat, a gamma secretase inhibitor from SpringWorks Therapeutics, and in consolidation therapy. We anticipate having updated data to share from the Allo 715 monotherapy arm of our universal trial by the end of the year, and we are on course to provide updates on Allo 715 in combination with Neurogastastat in 2022. We're also thrilled to be dosing patients in our IGNITE clinical trial with Allo 605, our first TurboCAR clinical candidate and part of our broader anti-BCMA strategy. TurboCAR represents a next-generation cell therapy with built-in cytokine signaling, eliminating the need for systemic cytokine administration and the potential to induce broader immune system stimulation. With TurboCAR, we anticipate being able to improve the potency and persistence of Allocard T cells while delaying exhaustion, traits that are key to our performance in both liquid and solid tumors. Finally, we're progressing in the dose escalation portion of the TRAVERSE trial, our first venture into solid tumors with ALOS316 in clear cell renal cell carcinoma. We expect to present data on this important program next year. I'd like to echo David in thanking you for your ongoing support. Our science and clinical teams are making consistent programs in advancing a promising portfolio of Allocard C candidates for patients in need. something that we could not achieve without the backing of the investment community. I'd like to now turn the call over to Eric for an update on our financials.

Thank you, and good afternoon. As I open my portion of the prepared remarks, I'd like to highlight progress made in our joint venture with Overland Pharmaceuticals to develop and commercialize our Allocarty therapies in Greater China, Taiwan, South Korea, and Singapore. In June, we announced the appointment of Dr. Shuyang Yao, as CEO of Allogene Overland BioPharm. Dr. Yao has over 15 years of experience in cell therapy and was most recently the Chief Scientific Officer and Head of Research and Technology Development of Wuxi Advanced Therapies at Wuxi Aptec, where he led new technology acquisition, development, translation, and application. We are delighted to welcome Dr. Yao to the team and are already seeing his presence translate into meaningful activities as we seek to bring the promise of allogeneic cell therapies to individuals with cancer in Asia. In the second quarter of 2021, our research and development expenses were $52.3 million, which includes $10.5 million of non-cash stock-based compensation expense. General and administrative expenses were $18.8 million for the second quarter of 2021, which includes $10.6 million of non-cash stock-based compensation expense. Our net loss for the second quarter of 2021 was $70.9 million, or 53 cents per share, including non-cash stock-based compensation expense of $21.1 million. As David and Rafael mentioned, we were on track to support five clinical trials during 2021, including the initiation of a pivotal trial for Allo 501A towards year end. We were also looking forward to initiating manufacturing at Cell Forge One, our Newark manufacturing facility. Overall, we continue to expect our full year 2021 operating expenses to be between $300 and $330 million, implying a meaningful ramp in expenses during the second half of the year. This includes an estimated non-cast stock-based compensation expense of $80 million to $90 million and excludes any impact from potential business development activities. With that, we will now open the call for your questions.

As a reminder, to ask a question, you will need to press star one on your telephone. To withdraw your question, press the pound key. We ask that you please limit yourselves to one question. Please stand by while we compile the Q&A roster. Our first question comes from the line of Michael Yee from Jefferies. Your line is now open.

Hi, good afternoon. This is Dennis staying on for Mike. I just have a quick question around the lymphoma data coming at year end. Can you just comment on what type of data we will get and specifically for consolidation? Can you help us kind of set expectations for that data relative to what we've seen at ASCO? Thank you.

Hi. This is David Chang. I usually take a lot of questions, but, you know, much of today's discussion I expect to be around CD19, and I'm going to ask our chief medical officer, Rafael, to comment on the expectations of what data we will be presenting at the year-end. Sure. So at the ASCO time point, we had 10 patients that had received consolidation, and we were pretty encouraged by what we saw. Eighty percent of patients are responding with seven out of the ten incomplete response. And more importantly, we saw conversions from PRs to CRs. So that gave us impetus to continue to accrue, and investigators have been very enthusiastic about the ability of consolidation to actually boost up complete response rates, which may be a surrogate to longer durability. So what you may expect towards the end of the year is longer follow-up on those ASCO patients, as well as more patients that we've continued to accrue, both on Alpha and Alpha 2. and follicular lymphoma, and diffuse lifestyle lymphoma. The durability will be variable, obviously, but at least we'll include those patients that we presented at ASCO. And I think, you know, there will be sufficient to obviously make a judgment as to the merits of consolidation. So I can't give you an exact number, but it will be obviously more volume of what we showed at ASCO because we've continued this approach.

Thank you. Our next question comes from the line of Salveen Richter from Goldman Sachs. Your line is now open. Pardon me, Salveen Richter from Goldman Sachs. Your line is now open. Please check your mute button. Our next question comes from the line of Mark Fram from Cowan & Company. Your line is now open.

Thanks for taking my questions. On your comments about defaulting to using the consolidation dosing, your kind of default assumption, would you expect that the pivotal trial is going to be just a single dose using that consolidation approach, a single arm or two? you might say FDA require a kind of a randomized trial for the consolidation piece of it to kind of definitively establish the utility of that second dose. And then I guess related to that, as you evaluate the early data that's coming out of the trial, just what's your latest thoughts on kind of the minimum kind of difference in durable CR rate that you need to see to justify that second dose?

Yes, Mark, those are very good questions. I mean, in general... The fact that one gives more than one dose of a product doesn't necessarily lead to a mandate from regulators to test single dose in a randomized fashion. Obviously, the agencies' negotiations need to happen. you know, just akin to, you know, what may happen with a vaccine or with a product that requires periodic dosing, whether it's every two weeks or every five weeks or, you know, dosing, you know, for a year or goes into progression, et cetera. The sponsor establishes the regimen and proposes that as the regimen to go forward. So I don't foresee that there will be a mandate for us to actually establish whether consolidation is better than single dose or not. It will be up to us to decide whether we believe that that is the case, which leads me to the second part of your question. The evidence would be a composite of the high CR rate. the durability of the responses, and we are accumulating more and more amounts on some of these patients, as I mentioned before, and also some of the surrogates, like minimal residual disease, and then the ability to continue to expand and observe persistence of the CAR positive cells, which we've already seen after the second dose. So, you know, so far we're excited about what we're seeing, and that's why we believe that it's likely that we will incorporate consolidation in our 2012 trial, but we'll continue to observe the data prior to making the decision. And Mark, this is Dave Chang. If I can add on to that, you know, I take it there will be a lot of questions about the study design that we will go forward with in the FDA meeting. And I kindly ask you to stay tuned. I mean, certainly we have to have the FDA discussion. And as we come out of it, we will clarify exactly what will happen for our pivotal study.

Thank you. Our next question comes from the line of Luca Isi from RBC. Your line is now open.

Oh, terrific. Thanks so much for taking my question. Congrats on all the progress. Maybe a quick one. I think Faith Therapeutics is planning to show some, for the first time, I think, clinical data for the CD19 CAR-NK cells in the next two weeks. I'm wondering if you can comment on what are your expectations getting into that data, and maybe a bigger picture, what's your latest thinking on the debate between CAR-T cell versus CAR-NK cells? Thanks so much.

Yeah, Luca, thank you very much for that question. Certainly, you know, our focus now is really advancing our allogeneic CAR-K program, allo501A, into the pivotal study. We have treated a number of patients, and, you know, we have a good understanding coming from the, you know, the large number of patients, the emerging data we have from the 501, where most of the single dose experience are coming from, as well as the consolidation dosing, which we are very interested in. As you know, the allogeneic cell therapy field is a very active place. I think a lot of companies see the promise of the off-the-shelf therapy with the potential of providing very deep and durable responses, and companies are taking different approaches. We believe in the CAR T therapy, especially therapy that leverages T cells, and we eagerly wait to see what, you know, other companies, especially those leveraging the NK cells, will provide in their data updates. So, you know, let's have another conversation after the, you know, data presentation, which I believe is planned for sometime in August.

Thank you. Our next question comes from the line of Salveen Richter from Goldman Sachs. Your line is now open.

Yeah, sorry for earlier. Just two questions here. Could you talk about CD7T and what you would see as a clinical bar here in First Data with your CAR-T program? And then on the BCMA side, do you have an understanding here of the optimization levers required to get you closer to the autologous profile?

Yes, Alvin, it's Rafael. So on CD70, you know, that program has begun not that long ago, and as you know, we have to treat patients and observe them before we can go through those escalations. We're treating patients that have failed all pathway-directed therapies, so that is checkpoint inhibitors and endogenous inhibitors. and many of them are progressing as they come into the study. So, you know, we hope to get some early evidence of potential activity that we can show next year. You know, in terms of the VAR, I think it's premature to talk about it, but, you know, many of these patients are already refractory, and as you know, you know, the data in solid tumors with CARs, you know, still needs to mature and progress. But I think certainly any complete responses or partial responses will be of interest and, you know, we will follow the field very closely. And there's a number of surrogate markers that, you know, we're also looking at that will help us with other targets in solid tumors, such as trafficking into the tumor, the tumor microenvironment effect, resistance, et cetera. In terms of BCMA optimization, we have continued dosing. As you know, we had, we were in DL4. We have finished our dose escalation. We've continued to follow patients. We are starting consolidation as well. And, you know, we were very glad to see the ARMA designation being awarded to the product and in part that was in recognition for, you know, the effect of the product, but also the ability to treat very quickly and to avoid breathing therapy, which are two important features that, you know, you don't see in the autologous setting. But we clearly want to get closer to the autologous bar. There's no question that SILTA cell has set a pretty high bar. And so we're continuing with consolidation, the use of neurovacistat, and obviously the tubocard. that we refer to in the prepared remarks that we just started. So, you know, it's a matter of staying tuned and seeing what these potential optimizations results are.

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

Hey, this is Kelsey on for Michael. Thanks for taking our question. Maybe building on the multiple myeloma side, I guess, what should we be expecting at ASH in terms of, you know, when you implemented the consolidation regimen? Will there be, you know, a meaningful amount of patients that we can interpret single agent versus consolidation? And would we see any initial data points from the near-gas-to-stat combination? That's it from me. Thank you.

Yeah, so the consolidation, Kelsey, started relatively recently. So there will be patients, but there may not be a long follow-up. There will be more follow-up on the higher doses, which we've already noted that were more effective on the lower doses. So we treated in DL3 and DL4. And so we will have more patients on those as well as longer follow-up. Neurogastastat is occurring well, but we will need, you know, to have sufficient patients and sufficient follow-up. And so we believe that that will probably be 2022 type data release, just like 605. So, you know, most likely it will be much more mature data with the higher doses on 715 that we will present towards the end of the year.

Perfect. Thank you. Thank you. Our next question comes from the line of Jason Gerberry from Bank of America. Your line is now open.

Hey, guys. Thanks for taking my questions. Another BCMA question, just heading into ASH. Do you, you know, obviously, as you guys have mentioned, autologous has set a high bar. Your data last year at ASH were immature for the 480 million cell dose. So I'm just curious, do you think You might be at a point at ASH to determine whether or not single dose is the right path forward or whether you need to shift the focus to gamma secretase or turbo carb programs or dose consolidation. Just sort of curious if you feel like the data might be mature enough for single dose to make that pivot or prioritization. Thanks.

Hey, Jason, thanks for the great question. I mean, I think you're asking all the right questions. I mean, certainly from the beginning, you know, we set up the DCMA program slightly different than the way that we set up the C-19 program. I mean, yes, there are different levers that, you know, we can test, including higher cell dose and more stronger lymphodepletion, leveraging what we have, specifically ALO647, and consolidation. And, you know, all these are the parameters that we tested in the CD19 program, and we have a lot of knowledge about how to best utilize different levers to optimize the benefits of, you know, ALO-715. Also, you know, we have, you know, taken a, you know, sort of somewhat unusual step of concurrently developing the next generation, ALO-605, that utilizes the turbo car technology. So, in terms of, you know, the question about, you know, when we will know about what to do with our different BCMA approaches that we are making, We've got to take all different information that we are generating, and all these trials are ongoing and enrolling patients, and we are in a pretty good position, I believe, that sometime in 2022, there will be a convergence of data that will help us to map out the path for the BCMA program.

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

Hi, guys. Thanks for taking the question. Follow-up on the last question, actually. Just curious, for L0715, in terms of combining with Neurogastastat, I'm wondering if you're considering giving multiple doses of Neurogastastat sometime in the future, if it may be beneficial to dose initially in combination with 715 and 647, and then maybe after that to give another dose or two. Just curious if that's something that you're considering for the future. Thanks.

Hi, John. This is Rafael. Yeah, good question. I mean, we haven't gone into how we're dosing Neurogastastat, you know, for competitive reasons, obviously. I mean, I can tell you that we don't just give one dose. And, you know, our intent is to try to maximize the benefit of BCMA expression that neurogas stats can afford. So, we will be testing, you know, the potential and, you know, it may take the form of several doses. And this is something that is currently under exploration. Stay tuned for the results.

Thank you. Our next question comes from the line of Mark Bridenbach from Oppenheimer. Your line is now open.

Hey, guys. Thanks for taking my question. Just a quick one from me. I know the main focus of the upcoming pivotal trial will be on large B-cell lymphomas, but I'm wondering if you have plans to continue development of 501A in follicular lymphoma, or is that off the table for now?

Yes, Mark. I mean, this is something that we are crafting right now, which is a comprehensive program that includes a suite of studies across various lines of therapies as well as histologies. As you know, there are second-line results that have come. come up and we are thinking about follow-on trials that would address that need with the allogeneic 501A therapy and likewise to follow on with follicular lymphoma and potentially other histologies. So right now we are very focused on the third line histology and in discussions and preparations to get that study started. but there will be a lot of activity around 501A to really form a comprehensive program.

Thank you. Our next question comes from the line of Ren Benjamin from JMP Securities. Your line is now open.

Hey, good afternoon, guys. Thanks for taking the questions and congrats on the progress. This is just one for me. When we go to ALO 316, can you just remind us why RCC as opposed to I'd say any other solid tumors. And when I think about RCC, I always, you know, think about in combination with checkpoints. And I guess I'm curious as to where you guys are in the development of evaluating these allogeneic cell therapies in combination with checkpoints, whether it's with RCC or any of the other indications or in the 501 test kitchen that you guys have.

Glenn, you know, great question. You know, as you're pointing out, with our ALO316 targeting CD70, there are several different development opportunities. CD70 as a target, it is very attractive in both heme as well as follow tumor indications. Certainly, renal cell carcinoma, and I'll go into why we chose the renal cell. as well as other types of tumors, cell tumors. And also, there's a lot of interest, and we're certainly getting a lot of inbound interest in advancing 316 in the AML indication, where there is some earlier proof of concept coming from using antibody alone for the treatment of AML. So we have many different options to consider. At the end, From the corporate perspective, we wanted to advance the allogeneic CAR T into the cell tumor, you know, which is the reason that we chose the renal cell as the first indication. And as a part of your question, I mean, is there an opportunity to combine CAR T therapy with a checkpoint inhibitor? I mean, that's definitely a topic that has been explored in other CAR T settings as well. We will be considering that. once we sort of generate the safety and efficacy data from the single agent treatment of LO316. And also at the same time, as we get more proof of concept from 316, stay tuned. We will be advancing that program into other indications as well.

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

Thanks for taking the question. I wanted to get your thoughts on, you know, the Zuma 7 trial and transform results as it relates to how the LBCL landscape might, you know, change by the time, you know, AL501 goes through its pivotal trial. Just curious to kind of hear the thoughts on, you know, CAR T's moving into earlier lines of therapy given the CAR T-naive data that you've shown to date. Thanks.

Raju, you know, thanks for that question. You know, I personally was involved in the Zuma 7 study, and I have to say that I was really thrilled when the, you know, the preliminary data came out, and certainly that highlights what the CAR-K therapy can do. I mean, there are a lot of questions about is the CAR-K therapy going to be just you know, for the relapsed refractory setting or can it move back to the earlier line? I think Zuma 7 study, you know, sets a clear example that the cardiac therapy can be more effective and work better in the earlier lines of therapy. And we see that as an opportunity, you know, for the allogeneic to follow what was set by the autologous cardiac therapy. You know, having been involved in both autologous and allogeneic cardiac therapy, As I said in the prepared statement, what we are seeing in the allogeneic CAR-T therapy coming out of the 501 and 501A data is, you know, so many consistencies with what we saw in the otolus CAR-T. I mean, that's one of the reasons that we are very, you know, I guess I'm not foolish and confident about the future of allo501A. And, you know, the future for LO501A will not stop in the relapse refractory setting. You know, we will definitely advance that to other indications, especially in the earlier lines, as Rafael has earlier alluded to.

Thank you. Our next question comes from the line of Dane Leon from Raymond James. Your line is now open.

Hi. Thank you for taking the questions. Congrats on all the progress. and looking forward to some of the updates later this year. One question for me, just wanted to focus on the primary inbound that we get in terms of your data set in aggressive B-cell lymphoma right now. And that's really focused on understanding the infection risk profile. I guess maybe a multi-part question here, sorry. One, could you just remind everyone how the lymphodepletion works for the consolidation regimen that you're now using that we should see more data on later this year? And then, two, maybe comment on your expectations for infection rates for that consolidation regimen relative to maybe what we saw reported around ASCO between the 90 milligram of ALA-647, which seemed to be a bit higher than the 60 milligram dose. And then lastly, how that could play into discussions with FDA about clinical trial design if you do go forward with the consolidation dose or not, what they would want to see in terms of maybe patient numbers to understand that infection risk potentially relative to other salvage line therapies for those patients. Thank you.

Thanks for the question, and this is a complex question, and I'll do my best to do it justice. So just to start with consolidation, we give dose intensity that is the same as the 90 milligrams that you've seen with a single dose, in that we give 60 milligrams in three doses upon the first infusion. And then on the second infusion, which is done after day 28, we gave 30 milligrams. So the total dose intensity is the same, but it's split into two doses. What we've been incredibly pleased with the tolerability of both the initial and the consolidation infusion. What we hear and what we see is that particularly with consolidation, patients do find there's been really no, you know, class effects and tolerability has been quite good to the point that, you know, we're considering whether this could be done as an outpatient. The overall infection risk, I mean, if you look at the USPI of the three products that are approved in the autologous setting, I mean, it's very clear that it is similar to the infection rates that we see, which is, you know, in the, you know, 20... It ranges between, you know, 19% to the mid-20% in terms of grade 3 plus infection rates. And that's really what we see. So we do not believe that the way that we're using all of 647 is leading to a higher rate of infection. And it's really a common feature, which is really... highlighted by, you know, the guidelines of how to treat these patients and how to prophylact them. And it is possible that, you know, the split dosing, you know, may lead to even lower rates. But this is something that we really have to wait and see. But even with the single dose, the rates have not been higher than what we see in your column, sir. And, Dane, if I can just add on to that, you know, As a clinician and as somebody who's been involved in the CAR-T study, I mean, I can understand some of the concerns that are being raised by, about the infection rate. But now, you know, we have treated over 100 patients across different programs with our allogeneic CAR-T, you know, our CAR-T501, 501A, and 715. And I think at this point, you know, the clinical data speaks for itself in terms of the infection rate that we are seeing. And I have to say that in 100 patients that we have treated, despite some of the concerns that are being raised, I mean, the data doesn't really indicate that the infection rate is any higher than what has been reported in those hours after therapy.

Thank you. Our next question comes from the line of Ben Burnett from Stifel. Your line is now open.

Hello. Good afternoon. This is Carolina Ibanez on for Ben. Thank you for the questions. For your solid tumor program with RLO316, how should we think of cell expansion data and what time points can we expect to be supported by tissue biopsy data?

So, we in 316 follow cell expansion the same way that we do in the rest of our programs, which is, you know, pretty closely early on, and then obviously we spread it out as, you know, time goes on, but we continue to follow until we, you know, cease to see cell expansion. The data are premature, and we haven't obviously, you know, shared any data with 316 yet. But we've seen cell expansion or cell persistence all the way up to six months and beyond. There is one feature of 316 that we've mentioned in the past, which is that it is expressing activated T cells. So we believe that the alloreactive T cells may express CD70 and may be susceptible to actually cell kill by the allogeneic carb-bearing cells. So it is possible that the persistence may actually be even superior, and this is something that we are looking at and taking a look very closely. So in terms of the tissue, we definitely want to see what's happening in the tissue, particularly migration of the CAR positive cells to the tissue. We do biopsies very early on at entry into the study and then, you know, within the first 10 days. And we look for CAR presence. We look obviously for CD70, PD1, PD01, and other markers to tell us what's happening with the tumor microenvironment. So far, the data are premature, but we are accumulating these results, and it will be part of what will be presented when the data matures. So stay tuned.

Thank you. Our next question comes from the line of Ask Zika Gunwarden from Truist. Your line is now open.

Hi, guys. Thanks for taking my questions. Just want to follow back up on allo, Selma 5, plus your gamma C-precision inhibitor. Guys, previously you did mention that you might see this data in early 2022, and I just want to check if that early part is still in play here. And if not, could you maybe give a little bit more granularity as to when? And then related to that, I guess besides response rates, MRD levels, soluble BCMA levels, et cetera, what other measurements and data can we expect in this first look of this combination that will help support the rationale for putting these two together? Thank you very much.

Yeah, I mean, we haven't said exactly when the data will be shown. I mean, we said it will be 2022. And I think we will make the decision once we consider that we have a meaningful data set. So stay tuned. All I can say running this excellent team is that accrual has not been a problem and that the execution continues actually at a very brief pace. So hopefully we'll accumulate data as soon as possible and be able to share it with you. Yeah, I mean, obviously we're looking at BCMA expression in the plasma cells. We're looking at soluble BCMA. We're looking at MRD. We're looking at persistence. We're looking at something that's important in this field also, which is extramedullary disease and the ability to prevent relapses outside of the bone marrow. But perhaps the most important factor is the mechanistic reason for giving Neurogastastat, which is, you know, do we actually see a meaningful increase in BCMA, and does that result in a better enhanced activity of the CAR T allocellular 5? And, you know, that's what we're focused on. But we're doing all the biomarkers that you mentioned.

Thank you. Our next question comes from the line of Kalpeet Patel from B. Reilly Securities. Your line is now open.

Yes, hi. Thanks for taking the question. Maybe one for David or Rafael. In the study for renal cell, obviously safety is a priority first, but At what dose level should we expect to see some signals of clinical activity based on your preclinical PK-PD modeling? And then can you remind us if the lymphodepleting doses that you're using in renal cell are essentially the same as what you use in your liquid tumor trials? Thanks.

Let me take those questions. From the preclinical to clinical, we all learned that in CAR T fields, it is not as predictable. So, in terms of what is to see in clinics, I mean, you know, it really has to be done in carefully planned clinical study, which is currently being done. So, stay tuned. I mean, you know, it could happen in the first dose level, or it could happen in the second. I mean, the planned dose is three dose levels in the 316 study. The second question... The administration of... The lymphodepletion for the thalassemia versus heme malignancies. You know, for different reasons, you know, I apologize for not answering the question. You know, we are trying to remain relatively silent on the lymphodepletion strategy that we are making. So just wait for the data presentation. And as we said in the pre-care statement, We expect 316 data presentation to occur in 2022, next year.

Thank you. That concludes our question and answer session. I would like to turn the conference back over to management for any additional comments.

Thank you. It's an exciting time for Allogene as we look ahead to two near-term events that begin the journey towards commercialization. the planned initiation of our first pivotal trial, and taking control of our manufacturing with Cell Forge One, our first world-class facility. With that, thank you for joining us today and for taking part in our journey to define the future of allogeneic cell therapy. Operator, you may now disconnect.

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