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spk11: Hello and thank you for standing by and welcome to Allogene Therapeutics' fourth quarter and year end 2021 conference call. At this time, all participants are in a listen only mode. After the speaker's presentation, there'll be a question and answer session. To ask a question during this session, you'll need to press star one 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.
spk08: Thank you, Operator, and welcome to all who have joined this call. After the market closed today, Allogene issued a press release that provides a business update and financial results for the fourth quarter and full year 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, Dr. Eric Schmidt, Chief Financial Officer, and a new voice on our quarterly calls, Dr. Allison Moore, Chief Technical Officer. During today's call, we will be making certain forward-looking statements. These may include statements regarding the success and timing of our ongoing and planned clinical trials, data presentations, regulatory filings, future research and development efforts, manufacturing capabilities, and 2022 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.
spk07: Thanks, Christine. And thank you all who have joined our call. I am very excited to talk about what we believe will be an important year for Allergen as we are working to advance three exciting clinical programs, from initiating our first pivotal trial in non-Hodgkin's lymphoma to progressing our mid-stage program in multiple myeloma to pivotal readiness and advancing our solid tumor clinical program to potential proof of concept. 2021 was both a year of significant pipeline achievement and unexpected challenge associated with the clinical whole, both of which played a meaningful role in moving allergens and the field of allergenic cell therapy forward. With our CD19 program, we demonstrated an important first for our field as the phase one data from our alpha trials continue to support the promise of our platform and our ability to provide safe and durable alternative to approve autologous CAR-T therapies in patients with relapsed refractory non-Hodgkin's lymphoma. Our next most advanced clinical program targeting BCMA is the leading allogeneic CAR-T program in multiple myeloma. Our universal study opened the door for this modality as the first and still only trial to demonstrate substantive profile concept for allogeneic CAR-T in this disease setting. While we are proud to have established profile concept safety and efficacy data in both lymphoma and myeloma, we are even more excited about the potential for allo-CAR-T products to overcome the inherent limitations of autologous therapies. Today's marketplace for autologous cell therapy is constrained by treatment delays supply limitations, and often a requirement that patients receive breathing chemotherapy. No matter how compelling the data on autologous therapies might be, they are of no value to the many patients who cannot gain access. With our Allocarti products, we have shown the ability to deliver treatments to patients within days rather than weeks. Patients who enrolled in our studies can be nearly guaranteed to receive our products. In the alpha trials, 98% of enrolled patients received our products within a median time of two to five days from enrollment to the start of treatment. By comparison, in trials deploying otitis therapies for non-oxygen lymphoma, up to 30% of patients who underwent successful leukapheresis for cell manufacturing was still unable to receive treatment due to interval disease progression while waiting for CAR T cell products or due to manufacturing failures. Treatment delays are even more critical in the multiple myeloma setting, as many patients with rapidly progressing disease require bridging therapy as they wait for the manufacturing of their autologous CAR T cells and those who are unable to tolerate effective breathing chemotherapy may not be considered candidates for autologous therapy. Shortening time to treatment and ensuring access for nearly all suitable patients is just the beginning of how we are leveraging the attributes of Allocard T product. Our first allogeneic candidates are only the beginning of product innovation in the field of Allocard T. Our next generation products based on our turbo car and other technologies are aiming to enhance the efficacy and safety of allogeneic cell therapy. Aside from the data presented in 2021 came an unexpected challenge, our clinical hold. While no company wants to be faced with a hold, the situation provided us the opportunity to retest our manufacturing processes and reconfirmed the quality of our product. In responding to and quickly resolving the hold, our team, under the deft stewardship of Rafael, demonstrated the quality of leadership, collaboration, innovation, and focus required to be a pioneer in the field of Alocarp. I am incredibly proud of the manner in which our employees rose to this challenge. In retrospect, This experience provided us with an insight that we believe will give us a competitive edge as we look to leave the field of allogeneic cell therapy. We look forward to sharing the results from our scientific investigation in a peer-reviewed forum. As we prepare for the next stage in our life cycle with a planned allofibro 1A hibidro trial for relapsed refractory large B-cell lymphoma in mid-2022, We are also determined to minimize hurdles that could create delays at the time of a biologic license application submission. This brings us to our technical operations, product sciences, and manufacturing organizations. From the beginning, we have maintained that having in-house manufacturing capabilities is key to controlling the delivery of off-the-shelf CAR T therapies faster, more reliably, and at a greater scale, and we have invested heavily in this area. Our state-of-the-art manufacturing facility in Newark, California, called Cell Forge One, is now fully operational and producing GMP material with the intent of supplying LO501A in our planned pivotal study. Our incredible technical operations team is led by Dr. Alison Moore. In early 2018, as we were forming Allogene, I knew Allison was the person I wanted as our chief technical officer. When you are building something that has never been built before, there is no blueprint. You need someone who knows technology operations inside out. Allison came to Allogene with over 25 years of experience in chemistry, manufacturing, and controls, or CMC, at Amgen and Genentech, from process and product development to manufacturing, supply chain, global operations planning, and CMC regulatory affairs. I am immensely proud to work alongside Alison and know there is no one better to navigate the evolving CMC landscape. We are excited to have her join the call today. I now would like to invite Rafael to preview our R&D priorities for the upcoming year.
spk06: Thank you. As David has noted, I would like to focus my remarks today on the year ahead and our clinical programs as we prepare for our pivotal trial targeting CD19 and advance our BCMA and CD70 programs. As most are aware, we issued a press release on January 10th announcing that the FDA had removed the clinical hold on our Allocard C clinical trials. After our extensive investigation, it was determined that the chromosomal abnormality detected in a single patient treated with Allo501A was unrelated to talent gene editing or allogene manufacturing process and had no clinical significance. The abnormality was not detected in any manufacturer Allocard T product or in any other patient treated with the same Allo501A small. The abnormality developed after the cell product was administered and in both regions of the T cell receptor and immunoglobulin genes known to undergo rearrangement as part of the T cell or B cell maturation process. During our hold, our engagement with study investigators was robust, and it was clear many were anxious for allogene to resume studies. We are pleased to have quickly resumed clinical trial activities and are enrolling patients focused on allo715 and allo605 for multiple myeloma and allo316 for renal cell carcinoma. We have completed accrual in the allo501 alpha study, and the study will now continue to assess longer-term patient follow-up. As such, we will be directing the full CD19 focus on allo501A and finalize with the FDA a registrational approach prior to starting the Pivotal Alpha 2 study. Prior to the start of Phase 2, we plan to resume enrollment in the Phase 1 study in order to offer Allocard T to patients in need. Our ultimate goal is to deliver the first approved Allogeneic Card T product. We remain on track to start our Alloc 501A Pivotal trial mid-year. One of the most commonly asked questions from investors is about pivotal trial design. Given the competitive nature of the field, we are prioritizing the finalization of our discussions with the FDA. We will share additional details in our single-arm 5018 study at the time of trial initiation. Separately, and as Alison will discuss, we're front-loading many of the activities that address evolving CMC requirements ahead of what would be needed for a potential BLA submission. We believe our lymphodepletion regimen is differentiated through the use of Allo647, our anti-CD52 monoclonal antibody intended to enable enhanced expansion and persistence of AllocardT product candidates. Separate from our single-arm pivotal trial with Allo501A, We also intend to launch a standalone registrational trial for allo647 at the time of the allo501a pivotal trial. This randomized trial, referred to as the EXPAND trial, is intended to demonstrate the safety of allo647 and its contribution to the overall benefit of the lymphodepletion regimen. Based on the data we have previously presented at medical conferences, we believe Allo647 enables a highly competitive product profile for patients with large visa lymphoma. We also remain very excited by the potential of our anti-BCMA program. Autologous CAR-T therapies targeting BCMA have recently shown unprecedented response rates, which appear well in excess of what has been achieved with any other modality in relapsed refractory myeloma. There are a few allogeneic BCMA programs in development with the potential to bring cell therapy to the large population of patients in need. This has been reinforced by discussions with investigators. Our multi-pronged strategy to address this opportunity includes the Phase I universal trial, which has cohorts evaluating Allo715 as a monotherapy, consolidated dosing, and the combination of Allo715 with Neurogastastat. The Phase I IGNITE trial evaluating all of 605 is our first TurboCard candidate, which allows cytokine activation signaling to be engineered selectively into CAR-T cells intended to improve the potency and persistence of allogeneic cells. Trial activity has resumed, and we plan to provide a BCMA program clinical update by the end of 2022. Findings from our universal trial on allo715 indicate that an allogeneic RT therapy can be delivered rapidly and without the need for bridging therapy to patients with refractory multiple myeloma, and that a single dose of therapy was capable of inducing deep response. We are pleased that allo715 as a monotherapy could achieve and maintain meaningful response rates similar to the approved autologous CAR-T therapy with a high rate of MRD negativity for patients achieving PGPR or better responses. The benefits of an allogeneic option are especially valuable in aggressive disease like relapsed refractory multiple myeloma, even with new potential therapies in the horizon. Through ample discussions with investigators, The need for more therapy options is clear, and they often emphasize that an allowable margin for efficacy is offset by benefits provided by the off-the-shelf alternative. Before I welcome Alison to discuss her technical operations, I would like to comment briefly on our clinical development of Allo316, our anti-CD70 Allocard T candidate for solid tumors. Clinical trial activities have resumed for our Phase I Traverse Trial, which is designed to evaluate the safety, tolerability, and antitumor efficacy of Allo316 in patients with advanced or metastatic clear cell renal cell carcinoma. Metastatic solid tumors have historically been a challenge regardless of treatment modality. The five-year survival rate for patients with advanced kidney cancer is less than 15%. These and the scores not only the unmet need, but also the necessity for scientific innovation. CAR-T therapies in general have faced significant challenges in solid tumors, which can be summarized in three areas, target recognition and selectivity, trafficking, and survival within the tumor. We're working to overcome these issues with our AlloCAR-T platform, including several next-generation approaches to overcome the inhibitory signals of the tumor microenvironment. Meanwhile, we look forward to generating data from our ongoing Phase 1 dose escalation trial. I would now like to turn the call over to Alison.
spk10: Thank you, Rafael. I've been fortunate in my career to build high-performing teams, bring multiple medicines to market, build state-of-the-art manufacturing facilities, and redefine the scope of process development. However, a career highlight and something I am most proud of has been the progress we've made in making aloe car tea a reality for patients. When I joined Allogene in 2018, we were a small team working to do something that had never been done before, create off-the-shelf car tea products for patients with cancer from the tea cells of healthy donors. Our first clinical data presentation in 2020 provided initial proof of concept for the industry, showing that our allogeneic products have the potential to improve patients' lives. It represented two years of rigorous work, creativity, problem solving, and collaboration. Understanding product quality is paramount to the development of safe and effective products. In our increasingly complex world of biopharmaceutical development, the design and control of product quality is far from simple, and we've seen time and time again in cell therapy how manufacturing delays or issues translate into patients not getting treatment. That is why excellent CMC science is so critical. It is the convergence of multiple disciplines coming together to solve some of our most difficult challenges. I've been fortunate to have worked on many modalities, including monoclonal antibodies, viruses, and bispecifics, but I'm particularly excited about advancing cell therapies. While we stand on the shoulders of the autologous pioneers, the field continues to evolve dramatically as the science, the industry, and regulators become increasingly sophisticated. The evolution is clear. In the emerging cell and gene therapy field, the CMC work toward a BLA submission cannot be an afterthought. It is critical for demonstrating the quality of our product the reproducibility of the process, and the control strategy. Any gaps or weaknesses can compromise the entire submission. In the development of monoclonal antibodies, for instance, teams may have years during phase two and phase three clinical development in which we could study performance of the process and methods and the opportunity to optimize production. In the development of CAR T therapy for late stage cancer, we have the privilege of starting pivotal trials relatively quickly following the recognition that these product candidates have game changing potential for patients. This expedited timeline is unique for CMC practitioners and ensuring the right experience within our teams is of utmost importance. Failure to understand the evolving landscape and FDA requirements can be a common pitfall and a cause of delay for new product approvals. The ability to produce safe and effective biologic products from complex raw materials is the difference between hope and reality for patients in need. While the start of any pivotal trial is exciting, approval is the ultimate goal. At Allogene, we are focused on mitigating risks as we look ahead to the BLA submission by moving up the timeline for important CMC validation work prior to the start of the pivotal program. This improves our measurement of quality attributes and enables robust characterization for approval. Drawn process and product validation support our ability to deliver a well-characterized biologic with minimized variability. We believe this will work to our advantage in the long term and set us up for success. Understanding a live product requires collaboration across many disciplines, including process development, clinical, research, translational sciences, and biometrics. I am so proud of the proactive work being done by our incredible team to eliminate the potential downstream delays and to, more importantly, be able to say with confidence that we can safely and effectively deliver to patients the promise of our Allocarti products. We look forward to advancing this important area of drug development. and building a robust regulatory dossier that effectively communicates the strategic design and strong execution of our CMC activities. I will now turn the call over to Eric.
spk15: Thank you, Allison. During meetings with investors, we often get a multitude of questions on manufacturing and the evolving gene and cell therapy CMC landscape. So we're quite privileged to have in Allison someone so experienced and visionary at the helm of our operations technology group. Before I provide a brief overview of our financials for the quarter and year end, I'd like to spend a few minutes on a topic that's been at the forefront of the industry in today's very challenging market environment, cash runway. We are very fortunate to be in a strong financial position, ending the year with $810 million in cash, cash equivalents and investments and no debt, As you may have been able to discern from comments by David, Raphael, and Allison, one of the most critical elements of our corporate and financial strategy is to efficiently deploy our capital resources to support value-enhancing programs that will drive long-term growth. In 2022, we have taken important measures designed to keep our cash burn below $300 million. This means focusing on our most critical activities, including number one, starting with our ALO 501A pivotal trial. Number two, capitalizing on the tremendous opportunity in multiple myeloma. And number three, continued exploration of the role of Allocarti in solid tumors. We strongly believe we have the operational capabilities, scientific prowess, and resources needed to succeed in all three. Taking into account the incremental investment needed to support our first pivotal trial and fully operationalize CellForge1, We expect our full year 2022 gap operating expenses to be between $360 million and $390 million, including estimated non-cast stock-based compensation expense of $90 million to $100 million. This guidance excludes any impact from potential business development activities. As we review our financials for 2021, for the full year of 2021, research and development expenses were $220.2 million, which includes $39.6 million in expenses associated with non-cash stock-based compensation. For the full year of 2021, general and administrative expenses were $74.1 million, which includes $41.2 million of non-cash stock-based compensation expense. For the full year of 2021, our net loss was $257.0 million or $1.89 per share, including non-cash stock-based compensation expense of $80.8 million. With that, we will now open the call for your questions.
spk11: Thank you. As a reminder, to ask a question, you'll need to press star 1 on your telephone. To withdraw your question, press the pound key. Our first question comes from Michael Yee with Jeffries. Your line is open.
spk14: Hey guys, thanks for the call and thanks for the update. We had two questions. One was appreciating all the color you discussed around CMC and manufacturing. I guess maybe you could shed some light without giving too much away competitively on what you're working on and what competitive advantage or what insights you can provide us on that advantage. that you would have confidence that you will start the pivotal CD19 study by midyear. In other words, you're commenting about all of this, and those are the gain factors. Maybe give us some color on that. And the second relates to later this year there's a myeloma update. Can you just remind us on expectations? Presumably that's mostly data on the first generation, but not likely to have real data on turbo car. Thank you.
spk07: Michael, this is David. Thanks for those two questions. Obviously, the CMC question, that's not something that we have spoken about in our previous earnings call. And also, this is an area that probably is very complex, and we don't want to tip too much of our head about revealing too much. But since Allison has joined in, I'll ask her to provide some high-level response to your questions about what's being done on the CMC side. Alison?
spk10: Thanks, David, and thanks, Michael. Yeah, obviously, on the CMC side, we are really excited to advance product from CellForge One. CellForge One was designed and built to support commercial supply And we're so excited that that is already generating GMT material. And we are working with the agency to ensure that we can realize our goal there of supply from Self-Forge One. Also, we are really interested and excited, as I described in my comments, to really demonstrate that we understand our product really well. We think that this helps all the way through development. It helps me provide the best support for our clinical colleagues, and it allows us to make modifications, optimizations, and refinements as we go towards BLA filing.
spk14: Thank you. It sounds like it's really about Cell Forge 1. That's a big part of it, given that that's going to support commercialization. And on myeloma?
spk07: Yeah, so, you know, just on that, I mean, you know, as Allison had said, you know, we are trying to front load as much CMC activity, you know, ahead of the VLA filings. So, you know, we are taking very careful measures to, you know, address what's known as well as potential issues that may come up down the line. And, you know, being able to launch the pivotal study with the materials coming from the CF1 is one of the big things that we are trying to do. So with that, on the myeloma data, you know, Rafael?
spk06: Yes. Thanks, Michael. So, as you know, we presented at ASH data on 43 patients, and in my remarks I spoke about how excited we were about the data and how, you know, it really compares very well to the approved product that's out there in terms of responses, VGPR+, as well as durability. The interesting thing is that the follow-up was actually not long, so we continue to follow up these patients and the durability may still improve. We are really excited about the fact that it's been really well received, both by investigators and non-investigator opinion leaders in terms of the results that are obtained with a product that essentially is able to treat virtually every patient as opposed to the autologous product. We look forward to providing an update. As I mentioned before, that would be towards the end of the year, and it would include the patients that we have treated with Neurogastastat. We are now treating, now that the hold is over, patients on 605, and depending on the number of patients and the follow-up, then we may be able to include some of those patients in that update towards the end of the year. So stay tuned. It's a really exciting program that... We are testing several approaches, and it will be a big decision point for us this year. Thank you.
spk11: Thank you. Our next question comes from Salveen Richter with Goldman Sachs. Your line is open.
spk01: Good afternoon. Thanks for taking my question. Could you just speak to the – the ongoing discussions that you're having at the FDA that have to be finalized prior to commencing the pivotal Alpha-2 trial? And then secondly, with the CD70 program, how should we think about what the bar is here for what you'd want to see for that to be kind of a positive step to then move forward?
spk07: Salvin, you're making my job easy. I can defer again to Rafael to answer both of those questions. Rafael?
spk06: Yes, so we've been having discussions with FDA during the whole, which, you know, I think speaks to, you know, the interest and mutual interest on moving this allogeneic program forward. And we, as you know, are co-developing allo647 as well. So, We have had discussions as well in terms of how to develop that product. And 647, you know, gives us a lot of precision with regards to lymphodepletion. But in order for it to be approved as co-development, the agency obviously requires evidence of benefit-risk. So those discussions are being finalized. We are actually quite advanced on them. and we are very confident that the study will start, the 501 study will start by midyear, followed shortly by the ALOS 647 trial. So both trials are going to be in execution mode, and obviously we are working very closely with Alison and her team to ensure that we work together in sync and that we finish this trial without any issues with regards to designs or any issues with regards to CMC that may jeopardize our ability to complete the trial. So stay tuned, but the discussions are proceeding according to plan, and we have full confidence on our ability to start by midyear. On the CD70 program, the CD70 program has resumed. It's a really exciting program. We had started treating patients and we're continuing now. There's excitement in the investigative community about this program. It's in renal cell carcinoma, as you know, but it's got a lot of potential in other solid tumors and hematologic malignancies. And with regards to the bar, as I said before, you know, these patients, unfortunately, once they fail checkpoint inhibitors and angiogenesis inhibitors, even if they get more than one line of therapy, their five-year survival is quite low, you know, in the order of 10%, 15%. So, obviously, it's early for us to have discussions with regards to what is it that would be you know, be a meaningful regulatory threshold for approval. But, you know, this is something that we will obviously evaluate as we see it. But clearly, investigators would be happy with response rates because really after patients are exhausting the therapies, There really isn't very much that works. So, you know, we will have those discussions once we know a little bit more. It's a little bit early in the program for us to be able to tell.
spk01: Thank you.
spk11: Thank you. Our next question comes from Tyler Vampuren with Cowan. Your line is open.
spk12: Hey, guys. Thanks very much for taking the questions. Related to the separate Allo647 registrational trial, beyond safety, can you provide more specifics on what needs to be demonstrated for approval? And then the second question is, it should allow you guys to comprehensively detail the safety profile and demonstrate if it's adding any safety events to the Allocarti regimen, which could be beneficial given the historical theoretical concerns of infections, right? So other than endpoints required for approval, is this a significant purpose of the trial in your eyes?
spk06: Yes, so as I said before, 647, we view it as a competitive advantage. As you know, lymphodepletion is critical in the allogeneic space, and 647 has provided us with incredible precision with regards to T cell depletion, which is required in the allogeneic setting for the avoidance of rejection But because it's co-development, and I've been involved in the development of many drugs, including co-development drugs, FDA requires the benefit risk to be shown and demonstrated for each one of the components, both 647 and 501A, so hence the second study that's required. It is going to be a randomized trial. They will compare it to FC. We are pretty confident that 647 leads to better outcomes and, you know, the need for lymphosuppression has been shown not just in our program but in other programs as well. And 647 has been a component that has been studied at multiple doses in our program. So we're very confident that this is a study that's going to show that 647 shows superiority to SC alone. And importantly, that the safety of it is actually important. you know, very comparable with regards to what you see in the autologous setting. So we haven't actually seen with the use of 647 more infections or grade three plus infections than are seen in the autologous setting. So you are absolutely right. We expect to demonstrate that 647 is superior to FC alone and also that the tolerability of FCA is on par with what's seen with autologous CAR-Ts.
spk11: Thank you. Our next question comes from Michael Schmidt with Guggenheim Securities. Your line is open.
spk09: Hey, this is Kelsey on for Michael. Thanks for taking our question. I guess just to confirm one thing, will there be any update on the Phase 1 data sets from the CD19 program? And then secondly, on BCMA, I guess, will you wait to see the Allo 605 data before making a go-forward decision for the franchise, or would you consider advancing both 715 and 605? Thank you.
spk07: Hi, Kelsey. I'm going to ask Eric to respond to both of your questions.
spk15: Eric? Thanks, Kelsey. In terms of the CD19 updates, yes, you can expect that we'll present a longer-term follow-up data set at some future medical meeting as we continue to observe and monitor patients that have been previously dosed in that study. We don't exactly know the form for that yet, but just as a reminder, we've been Really pleased with the durability in particular that we have been able to show as of the ASH data cutoff, gratifying to see 10 out of the 14 patients who achieved a complete response still in a complete response. So we're keen to see just how much longer those responses can last. And then on your second question, the evaluation of our BCMA program, it's nice to be back in control of this program, back in the clinic with the ability to execute across our multi-pronged strategy. And yes, we think 2022 is going to be a critical year for generating data sets across many of our strategies. And hopefully by the end of the year, as Rafael has already mentioned, we'll have enough data to begin to make a decision on next program steps.
spk09: Got it. Thank you.
spk11: Thank you. Our next question comes from Mark Breedenbaugh with Oppenheimer. Your line is open.
spk03: Hey, guys. Good afternoon. Thanks for taking the question. I know you said you wouldn't tell us much about the pivotal study design, but I'll try anyway. Just given the closeness between the ORR and the CR rates you've seen in Alpha 2, I'm wondering if you're currently viewing CR rate as a potential or likely registrational endpoint in that study, and if so, I'm just wondering if you can point us to any precedents that have recent approvals in DLBCL or large B-cell lymphomas that might serve as kind of a model to build this trial after. Thank you.
spk07: Mark, let me take on that question. So as Rafael has said, ALO501A, you know, that's proceeding as a single pivotal study. And in any single study, two important, you know, elements of the efficacy measure is the response rate or objective response rate. And then the second one is the durability of the response. So, you know, that has been part of the discussion with FDA, and, you know, we expect that those two, primary and co-primary, you know, endpoint will be the key way, you know, measures of efficacy. And certainly, you know, safety is another part, you know, which will be also part of, you know, I expect to be the data review.
spk03: Okay, super helpful. Thanks for taking the question.
spk11: Our next question comes from Ren Benjamin with JMP Securities. Your line is open.
spk02: Hey, good afternoon, guys. Thanks for taking the questions. There's two for me. Just going back to the ALO647 study, can you talk a little bit about, you know, if for some reason, you know, it's a randomized study and that trial fails, how that might impact the entire application of 501A and 502A? 647. And if it works, just, you know, kind of thinking out of the box here, could this, you know, could this be used as a general lymphodepletion regimen, potentially even with autologous therapies? It's almost, you know, sold sort of separately. And then just something for, I'm sure this is more for Eric, just a status update on the development partnerships. The ones that interest me in particular are NOTCH and your recent collaboration with Antion I'm kind of curious, you know, when you're striking these relationships, is this something that, you know, well, how do you plan on uncovering the value, or is this just something that you want to, you know, kind of keep abreast on because it's pretty novel new technology? And any update on Overland, the joint venture, if there's a deliverable this year we can keep track of? Thanks. Thanks.
spk07: So, you know, all three great questions. You know, the question about the 647, you know, this is drug co-development where we have to demonstrate the contribution of 647 to lymphodepletion. This is an area that we have, you know, at this point more than, you know, enough data set coming from both CD19, 501, 501A program, as well as multiple myeloma program. Certainly there is a possibility of study failure, but all the information that we have right now, we feel very comfortable and confident that the study will demonstrate the contribution of 647 in a meaningful way. And the second question, this is something that we frequently have a discussion internally. which is really how can we best leverage the potential benefit of 647, not just in our own allogeneic setting, but can it extend to other settings such as autologous. I would not rule that out, but for now our main focus is optimizing the use of 647. And also in some of our studies, we are trying to see whether we can tease out and lower the chemotherapy-based lymphodepletion, you know, moving more towards the biologic lymphodepletion, which we find to have, you know, several benefits. So that will be our, you know, initial attention. But certainly your question of, you know, can this be used in an autologous setting is something that we are also looking into. But, you know, that will not be immediate. And, you know, third question I'm going to ask, you know, Eric, to respond to. Okay, thanks, Rand.
spk15: I guess I'll get your third question, all three or four or five subparts, however many were in there, relating to our technology partners. Yeah, at this point in time, we've formed a number of relationships that we really feel give us as much access to gene engineering and cell engineering as we could probably want, including some of the relationships you've mentioned with Notch, Antion, and the joint venture, but others that have been undisclosed that provide additional domain expertise and engineering modality relationships. In terms of Notch in particular, where we're looking at the ability to make fully functional T-cells from an IPSC source, that partnership is going really quite well. Notch has made a lot of progress in the almost two years now since we've been working with them. And much of the work is focused on continued engineering and scale-up of their product. On the Antion side, a new relationship for us where we're partnering to look at their multiplex knockdown technology to add greater functionality to some of our gene and cell engineering capabilities. Very new relationship, but we view them as leaders in this space and very pleased that we think Allogene will be a focus project for them. And lastly, I'm a joint venture with Allergy and Overland in China, giving us access to an important commercial territory. That entity has begun building out a manufacturing facility in China, which will be required to commercialize our therapies, and they're making quite good progress as well. We'd hope to be able to launch that facility later this year. Thank you for the question. Thank you.
spk11: Thank you. Our next question comes from Luca Issi with RBC. Your line is open.
spk05: Oh, great. Thanks so much for taking my question. Maybe on six or seven, you know, obviously the FDA is asking you to start a contribution of six or seven. Is this something that is just limited to non-autistic lymphoma, or should we expect the FDA may ask you for similar trials also for multiple myeloma and solid tumors? And then maybe on business development, we've seen a couple of deals recently where companies have decided to monetize some of their extra manufacturing capability to extend the runway to including Atara, Fujifilm, or Homology Oxford. So wondering what was your reaction to those deals, and this is something that you may consider. And lastly, for CD70, I think I've seen on clinicaltri.gov that the size of Traverse actually has increased from 48 patients to 120 patients a couple weeks back. So wondering if you have any color on that. Thanks so much.
spk07: Okay, the first question. Yeah, so the 647, you're asking whether for different indications there's a need to do additional studies. I mean, we see the lymphodepletion as something that is, you know, generalizable and extendable to other indications. I mean, that's our current position. We have not had any specific discussion with the regulatory agencies about how to deal with the contribution of 647 for depletion in different indications. So, you know, stay tuned.
spk15: On our manufacturing plans, Luca, no, is the short answer there. As you heard from Allison Moore, we view ownership of the CF1 facility or Self-Forge 1 facility as absolutely critical to our ability to function and commercialize across a slew of product opportunities. So given our strong cash position, $800 million plus, we don't see any need or interest in monetizing that in any way, shape, or form, just the opposite. We're going to continue to invest And then on the traverse, clinicaltrials.gov listing, I wouldn't read much into that, honestly. The clinical team often includes a number of different parameter changes to our studies, and those changes are designed to provide the utmost in flexibility going forward. But certainly we don't have plans at this stage to enroll the full cohort of patients that you referenced.
spk11: Thank you. As a reminder, in the interest of time, please limit yourself to one question. Our next question comes from Ashika Gumardin, with Truist. Your line is open.
spk16: Hi, guys. Thanks for taking the questions. I want to pick on Allison, since she's on the call today, if I may. Alison, a while back in discussion we were talking about the goal of the allogeneic cell therapies is to get maybe around 1,000 or more batches out of a single donor draw. But you had some ways to go in reaching that. And a little while back, I think I remember you telling us that you were getting around maybe 100 batches per draw. Where are you on that today? And then also religion, more generally. are you able to get these incremental innovations to manufacturing incorporated into the production of cell therapies that are already in the clinic, or does that essentially require a lot of new work and maybe even a new IND? Thanks.
spk10: Thank you. Yes, great question. So our goal at Allotine has been to, from... a single leukophoresis enable approximately 100 doses. That has been our goal. That's still what we are working towards. I can say that we know that we can do that. And already we have been very successful in optimizing yield. And I think that our focus right now is to ensure supply across all of these programs, but certainly as a process developer, I can see that there is extensive potential for us to continue to optimize yield. So I would answer you by saying that we have more than an adequate performance there in terms of doses But there's definitely the opportunity for further improvement there in the future. Then regarding your question with respect to the introduction of novel technologies, this is certainly not just a question. This is a question across all biologics products. And it really relates to the magnitude of the technology change and how well you understand your product and your process. And we certainly have been able to introduce some novel technologies that we're very excited about, but we will always do that in collaboration with the agency and with the very best analytical measures. And that's why focusing on product quality and the measurement of product quality is always in our best interest.
spk16: Great. Thanks for the call. I appreciate that.
spk11: Thank you. Our next question comes from John Newman with Canaccord. Your line is open.
spk18: Hey, guys. Thank you for all the information on the call, and thank you for taking my question. So my question is just wondering if you're confident that you can get the patient population in the pivotal study that is representative of of patients that are currently receiving the autologous therapies. And the reason I'm asking is I feel like you're, you know, some of the most recent updates, you've had some patients that have already had treatment with CD19 therapies and failed them. And I feel like to get a true, accurate picture of the true potential of this product, the LL501 product, the agency might, be curious as to what it looks like in a population similar to the autologous therapy. So without getting into too much detail about the design, just curious if you're confident that you'll be able to do that in a pivotal trial. Thanks.
spk06: Thanks, John, for the question. It's a great question. I can tell you that in a phase one study, you know, we go through a variety of clinical trials, situations with regards to the kinds of patients that we enroll. So, you know, one of the questions, obviously, is what happens to patients that have received C19-directed therapy as an example, which you mentioned. That doesn't mean that the population that we put in the Phase 1 study where we're looking at doses and we're looking at populations, et cetera, is going to be the one that is actually in the pivotal study. So those discussions, as I said, will take place and have been taking place with FDA. But we fully expect, and our investigators are backing us up with regards to this, that they will be representative of the patients that are entering to autologous therapies with the caveat that, obviously, they will enter sooner and, obviously, they won't need aphoresis and will be able to get the therapy the majority of the patients. So we have actually no doubt that this is achievable.
spk11: Thank you. Our next question comes from Raji Prasad with William Blair. Your line is open.
spk13: Thanks for the question. Just wanted to get a sense of the bar on the BCMA program in terms of maybe patient numbers and durability. at the kind of go-forward dose that you're looking at before taking whichever program forward. Just curious to know how much data that you need from the Neurogastet program as well as 605 to really make that decision and how much the potential, you know, efficacy improvements of the approved autologous therapies if Sotosol is approved on the 28th plays a role into kind of the decision-making process. Thanks.
spk07: Great question. I'm going to ask Eric to respond to that.
spk15: Yeah, thanks for that, Raj. So, you know, first, again, I think we're in a fortunate position to be evaluating multiple different strategies, starting off with a strong foundation with what we've already shown on LS715. And, you know, specifically there, as Rafael has already commented, that 715 profile essentially being right on par with the approved autologous therapy. So, obviously, we're trying to build off that foundation with either, you know, the combination approach that you mentioned or consolidation therapy or the Allo 605 turbo car that we're also very keen on. In terms of where the bar is going forward, you referenced, I think, the CiltaCell Pedufidate, which is upcoming here. We and everyone else are very persuaded by the compelling results that Johnson and Legend have been able to produce with that product. I think it really highlights what's possible with an autologous cell therapy, and the results are unprecedented, but You know, it also is quite clear that even the most efficacious drugs are impotent if they can't be delivered to patients in need. And as you know, the current market for autologous therapies is quite capacity constrained. And while we would expect supply to increase, we don't know by how much with that approval. And even more importantly, the autologous cell therapies are unlikely to ever be applicable to certain patient subset populations, specifically I guess I'm thinking about those patients who can't wait the weeks to months to be scheduled for collection and manufacturing, and also those patients who can't tolerate the bridging chemotherapy, which is being given to the majority of patients in the autologous studies. So, you know, for those reasons, we really think we have a pretty clean opportunity with our off-the-shelf product, and we're very focused on making the most of that opportunity as we collect the data and move forward.
spk11: Thank you. Our next question comes from Jason Gerberry with Bank of America. Your line is open.
spk04: Hi, this is Perry on the line for Jason. Thanks for taking our question. Two parts. One is regarding manufacturing. The other is kind of on the broader BCMA development. So for in-house manufacturing, I guess, are you expecting your in-house capabilities to fully support, both the pivotal as well as the commercial demand for 501? And then also, does in-house manufacturing address vector supply, or is that something that's parted with a third-party manufacturer? And then regarding BCMA development, you know, think about the broader spaces. Some of the autologous market leaders are moving into the third line setting, potentially having data by the time that you start a pivotal in one of your approaches. And I'm wondering, is there potential to start a pivotal trial in the third line setting, given the way that the space is evolving towards earlier lines? Thanks. Thanks.
spk07: Allison, do you want to take the manufacturing question?
spk10: I'll take the manufacturing question very quickly. Our facility is designed and built to be focused on CAR T at this time, although the build is modular and we could do other things in addition. And the answer is yes, it will have the capacity to supply commercial product for 501 . Regarding other raw materials, including critical raw materials, we have a broad network of third-party suppliers that we work with on a daily basis.
spk06: I think the point that you make about BCMA is a good one. These therapies will make their way into earlier lines of therapy. Yeah, as you know, they start in later lines of therapy first, but just like we plan to do in lymphoma, once we make the decision, then we will be developing a comprehensive program on BCMA.
spk11: Thank you. In the interest of time, we can take one more question, and that is from Dane Leone with Raymond James. Your line is open.
spk17: Thanks for taking the questions. One kind of interrelated question. Do you, and this is just something we get asked almost in every meeting with investors, do you have an updated view on the impact of prior CD19 therapy, like tapacitumab, within the lymphoma program?
spk00: That was an outstanding question that continues to be asked.
spk17: discussed since the presentation, the update of the alpha program during ASH. And within that vein of developing in multiple myeloma, does your team have a view of why or why not prior CDBCMA-targeted therapy would have a similar potential detrimental effect in responses to an allogeneic cell therapy product like has been discussed in lymphoma with CD19. Thank you.
spk06: Yeah, with regards to CD19 biotherapy, I mean, the data in autologous is actually, you know, very telling as well. Many patients do not respond, particularly if they were primary refractory or they relapse relatively quickly. And this is something that we are seeing as well in the allogeneic setting. So, We are not keen on enrolling these patients, you know, going forward. With regards to BCMA, we actually don't have much experience with BCMA-experienced patients, so we can't really answer the question that, you know, whether there are parallels with 319 in BCMA. I think that's a question to be answered, but, you know, currently we plan to study BCMA-9 patients.
spk11: Thank you. That concludes the question and answer session. I would like to turn the conference back over to management for any additional comments.
spk07: Thank you again for joining the call today. Based on our strong execution since inception, coupled with healthy cash position and our focused approach on drug development, I believe we remain positioned to transform and lead the field of LGA CAR-T. We look forward to sharing our continued progress with you throughout the year. Operator, you may now disconnect.
spk11: Thank you. Ladies and gentlemen, thank you for your participation in today's conference. This concludes the program. You may now log off and disconnect.
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