Earnings Call Transcript - ALLO Q4 2021

Operator, Operator

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 speakers' presentation, there will be a question-and-answer session. Please be aware that today's conference call is being recorded. I would now like to turn the call over to Christine Cassiano, Chief Communications Officer. Ms. Cassiano, please go ahead.

Christine Cassiano, Chief Communications Officer

Thank you, operator, and welcome to all who have joined the 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 call, Dr. Alison 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.

David Chang, President and CEO

Thank you, Christine, and thank you to all who have joined our call. I am very excited to talk about what we believe will be an important year for Allogene, 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 challenges associated with a clinical hold, both of which played a meaningful role in moving Allogene and the fields of allogeneic cell therapy forward. With our CD19 program, we demonstrated an important first for our field as the Phase 1 data from our ALPHA trials continued to support the promise of our platform and our ability to provide safe and durable alternatives to approved autologous CAR T therapies in patients with relapsed/refractory non-Hodgkin’s lymphoma. Our next most advanced clinical program targeting BCMA is a 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 proof of concept for allogeneic CAR T in this disease setting. While we are proud to have established proof of concept, safety and efficacy data in both lymphoma and myeloma, we are even more excited about the potential for AlloCAR 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 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 AlloCAR T 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 autologous therapies for non-Hodgkin's lymphoma, up to 30% of patients who underwent successful leukapheresis for CAR manufacturing were still unable to receive treatments due to manufacturing failures. Treatment delays are even more critical in the multiple myeloma setting as many patients with progressing disease require bridging therapy while they wait for the manufacturing of their autologous CAR T cells, and those who are unable to tolerate effective bridging 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 AlloCAR T products. Our first allogeneic candidates are only the beginning of product innovation in the field of AlloCAR T. Our next-generation products based on our TurboCAR and other technologies are aiming to enhance the efficacy and safety of allogeneic cell therapies. Aside from the data presented in 2021, we faced unexpected challenges with 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 reconfirm the quality of our products. In responding to and quickly resolving the hold, our team, under the stewardship of Rafael, demonstrated the quality of leadership, collaboration, innovation, and focus required to be a pioneer in the field of AlloCAR T. I am incredibly proud of the manner in which our employees rose to this challenge. In retrospect, this experience provided us with the insight that we believe will give us a competitive edge as we look to lead 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 lifecycle with our planned ALLO-501A Pivotal trial for relapsed refractory large B cell lymphoma in May 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 organization. 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. We have invested heavily in this area. Our state-of-the-art manufacturing facility in New York, California, called Cell Forge 1, is now fully operational and producing GMP material with the intent of supplying our 501A planned pivotal study. Our incredible technical operations team is led by Dr. Alison Moore. In early 2018, as we were forming Allogene, I knew Alison 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. Alison came to Allogene with over 25 years of experience in chemistry, manufacturing, and controls at Amgen and Genentech, covering 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.

Rafael Amado, Executive VP of Research and Development and Chief Medical Officer

Thank you. As David noted, I would like to focus my remarks today on the year ahead and our clinical programs as we prepare for a pivotal trial targeting CD19 and advanced BCMA and CD70 programs. As most are aware, we issued a press release on January 10, announcing that the FDA had removed the clinical hold on our AlloCAR T clinical trials. After our extensive investigation, it was determined that the chromosomal abnormality detected in a single patient treated with ALLO-501A was unrelated to gene editing or other manufacturing processes and had no clinical significance. The abnormality was not detected in any manufactured AlloCAR T product or in any other patients treated with the same ALLO-501A. The abnormality developed after the cell product was administered and in both regions of the T cell receptor and immunoglobulin gene known to undergo rearrangement as part of T cell maturation. During our hold, our engagement with study investigators was robust, and it was clear many were anxious for Allogene to resume study activities. We are pleased to have quickly resumed clinical productivity and are enrolling patients focused on our ALLO-715 and ALLO-605 for multiple myeloma, and ALLO-316 for renal cell carcinoma. We have completed accrual in the ALLO-501A study, and the study will now continue to assess longer-term patient follow-up. As such, we will be directing our focus on our ALLO-501A and finalizing with the FDA our registration approach prior to starting the pivotal study. Before the start of phase 2, we plan to resume enrollment in the Phase 1 study in order to offer AlloCAR T to patients in need. Our ultimate goal is to deliver the first approved allogeneic CAR T product. We remain on track to start our ALLO-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 501A study at the time of trial initiation. Separately, and as Alison will discuss, we're front-loading many of the activities that address evolving CGMP requirements ahead of what would be needed for a potential BLA submission. We believe our need for the patient regimen is differentiated through the use of ALLO-647, an anti-CD52 Monoclonal Antibody intended to enable enhanced expansion and persistence of AlloCAR T candidates. Separate from our single-arm pivotal trial with ALLO-501A, we also intend to launch a standalone registrational trial for ALLO-647 at the time of the ALLO-501A pivotal trial. These randomized trials, referred to as the Expand trial, are intended to demonstrate the safety of ALLO-647 and its contribution to the overall benefit of the lymphodepletion regimen. Based on the data we have previously presented at medical conferences, we believe ALLO-647 enables a highly competitive product profile for patients with large T cell lymphoma. We also remain very excited by the potential of our anti-BCMA program. ALLO 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. Yet, there are 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 1 Universal trial, which has cohorts evaluating ALLO-715 as a monotherapy, consolidative dosing, and the combination of ALLO-715 with additional modalities. The Phase 1 IGNITE trial evaluating ALLO-605, is our first TurboCAR candidate, which allows cytokine activation signaling to be engineered selectively into CAR T cells intended to improve the potency and persistence of allogeneic stem cells. All activity has resumed, and we plan to provide BCMA program clinical updates by the end of 2022. Findings from our UNIVERSAL Trial on ALLO-715 indicate that allogeneic CAR T therapy can be delivered rapidly, addressing the need for bridging therapy to patients with refractory multiple myeloma, and that a single dose of therapy was capable of inducing a deep response. We are pleased that ALLO-715 as a monotherapy could achieve or maintain meaningful response rates similar to the approved autologous CAR T therapies with a high rate of MRD negativity for patients achieving VGPR 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 on the horizon. Through ample discussions with investigators, the need for more therapy options is clear, and they often emphasize that an allogeneic margin for efficacy is offset by the benefits provided by the allogeneic alternative. Before I welcome Alison to discuss our technical operations, I would like to comment briefly on our clinical development of ALLO-316, our anti-CD70 AlloCAR T candidate for solid tumors. Clinical trial activities have resumed for our Phase 1 traverse trial which is designed to evaluate the safety, tolerability, and anti-tumor efficacy of ALLO-316 in patients with advanced 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%. This underscores not only the unmet needs 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 are 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.

Alison Moore, Chief Technical Officer

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 AlloCAR T 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: creating off-the-shelf CAR T products for patients with cancer from the T 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 receiving 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 bispecific products, 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 2 and Phase 3 clinical development in which we could study performance of the process and methods and have 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. Strong 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 potential downstream delays and, more importantly, to confidently state that we can safely and effectively deliver to patients the promise of our ALLO CAR T 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.

Eric Schmidt, Chief Financial Officer

Thank you, Alison. 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 someone as experienced and visionary as Alison 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: the very challenging market environment and cash runway. We were fortunate to end the year with $810 million in cash, cash equivalents, and investments with no debt. As you may have been able to discern from comments by David, Rafael, and Alison, 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 starting our ALLO-501A pivotal trial, capitalizing on the tremendous opportunity in multiple myeloma, and continued exploration of the role of ALLO CAR T 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 Cell Forge 1, we expect our full year 2022 GAAP operating expenses to be between $360 million and $390 million, including estimated non-cash 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, 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 totaled $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.

Operator, Operator

Thank you. Our first question comes from Michael Yee with Jefferies. Your line is open.

Michael Yee, Analyst

Hey, guys. Thanks for the call and thanks for the update. We had two questions. One was regarding 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 have confidence that you will start the pivotal CD19 study by mid-year? In other words, you're commenting about all of this and those are the key 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 TurboCAR? Thank you.

David Chang, President and CEO

Hey Michael, this is David. Thanks for those two questions. Regarding the CMC question, that's not something that we have spoken about in previous earnings calls. And also, this is an area that is very complex, and we don't want to reveal too much. But since Alison has joined, I'll ask her to provide some high-level response to your questions about what's being done on the CMC side. Alison?

Alison Moore, Chief Technical Officer

Thanks, David, and thanks, Michael. Yes, obviously, on the CMC side, we are really excited to advance product from Cell Forge 1. Cell Forge 1 was designed and built to support commercial supply, and we're so excited that it is already generating GMP material. We are working with the agency to ensure that we can realize our goals of supply from Cell Forge 1. 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 provide the best support for our clinical colleagues, and it allows us to make modifications, optimizations, and refinements as we go toward BLA filing.

Michael Yee, Analyst

Thank you. It sounds like it's really about Cell Forge 1, that's a big part of this given that that’s kind of supporting commercialization. And then on myeloma?

David Chang, President and CEO

Yes. So just on that, as Alison had said, we are trying to front-load as much CMC activity ahead of the BLA filings. We are taking very careful measures to address known potential issues that may come up down the line. Launching the pivotal study with materials coming from CF 1 is one of the big things that we are trying to do. So with that on the myeloma data, Rafael?

Rafael Amado, Executive VP of Research and Development and Chief Medical Officer

Yes, thanks, Mike. As you know, we presented data on 43 patients at ASH, and in my remarks, I spoke about how excited we were about the data. 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 very well received by investigators and key opinion leaders in terms of the results obtained with a product that can essentially treat virtually every patient as opposed to the autologous product. We look forward to providing an update towards the end of the year. It would include the patients treated with nirogacestat. We are now treating patients with ALLO-605, and depending on the number of patients from the follow-up, we may be able to include some of those in that update. 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.

Michael Yee, Analyst

Thank you.

Operator, Operator

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

Salveen Richter, Analyst

Good afternoon. Thanks for taking my question. Could you just speak to the ongoing discussions that you're having with the FDA that have to be finalized prior to commencing the pivotal ALPHA2 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?

David Chang, President and CEO

Salveen, you're making my job easy. I can refer to Rafael to answer both of those questions. Rafael?

Rafael Amado, Executive VP of Research and Development and Chief Medical Officer

Yes. We've been having discussions with the FDA during the fall, which I think speaks to the mutual interest in moving this allogeneic program forward. As you know, we are co-developing ALLO-647 as well, so we have discussed that product. And 647 gives us a lot of precision with the lymphodepletion regimen. In order for it to be approved as co-development, the agency requires evidence of benefit-risk. So those discussions are being finalized. We’re quite advanced on them and we are very confident that the ALLO-501A study will start by mid-year, followed shortly by the ALLO-647 trials. 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 finish this trial without any design issues that may jeopardize our ability to complete the trial. Stay tuned, but the discussions are proceeding according to plan, and we have full confidence in our ability to start by mid-year. On the CD70 program, the CD70 program has resumed, and there's real excitement in the investigator community about this program, which is in renal cell carcinoma, but it has a lot of potential in other solid tumors and hematologic malignancies. Regarding what is a meaningful regulatory threshold for approval, this is something we will evaluate as we learn more, but clearly, response rates are critical since patients typically have very low survival rates after failing treatment.

Salveen Richter, Analyst

Thank you.

Operator, Operator

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

Tyler Van Buren, Analyst

Hey, guys, thanks very much for taking the questions. Related to the separate ALLO-647 registrational trials beyond safety, can you provide more specifics on what needs to be demonstrated for approval? And then the second question is, does your in-house manufacturing address vector supply, or is that something that's partnered with a third-party manufacturer? Lastly, does your team have a view of why or why not prior CD19 or BCMA-targeted therapies would have a similar potential detrimental effect on responses to an allogeneic cell therapy product?

David Chang, President and CEO

Yes, so as we said before, ALLO-647, we view it as a competitive advantage. Ablation is critical in the allogeneic space, and 647 has provided us with incredible precision regarding T-cell depletion, which is required in allogeneic settings to avoid rejection. Since it's co-development, we need to demonstrate the contribution of ALLO-647 to lymphodepletion in a randomized trial, comparing it to the positive control. We are pretty confident that 647 leads to better outcomes. As for your question about BCMA and CD19, we have not had much experience with BCMA-experienced patients, so we can't answer the question on conflicting responses. However, we are currently focused on studying these patients and will explore those questions as we proceed.

Operator, Operator

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

Unidentified Analyst, Analyst

Hey, this is Kelsey on behalf of Michael. Thanks for taking my question. I just want to confirm if there is going to be an update on Phase 1 dataset for the CD19 program. Then secondly, on BCMA, will you be ready 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.

Alison Moore, Chief Technical Officer

Hi, Kelsey. I'm going to ask Eric to respond to both of your questions. Eric.

Eric Schmidt, Chief Financial Officer

Thanks, Kelsey. In terms of the CD19 updates, yes, you can expect that we will present a longer-term follow-up dataset at a future medical meeting as we continue to observe and monitor patients who have been previously dosed in that study. We don't know the forum for that yet, but we have been pleased with the durability in particular that we have been able to show as the ASH data cutoff. It's gratifying to see 10 out of the 14 patients who achieved a complete response still in that complete response. For your second question regarding evaluating our BCMA program, it's nice to be back in control of this program and executing across our multi-pronged strategy. We think 2022 is going to be critical for generating datasets across many of our strategies, and hopefully by the end of the year as Rafael mentioned, we'll have enough data to make a decision on next program steps.

Unidentified Analyst, Analyst

Got it. Thank you.

Operator, Operator

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

Mark Breidenbach, Analyst

Hi guys. Good afternoon. Thanks for taking my 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 CRS you've seen in ALPHA2, I'm wondering if you're currently viewing CRA as a potential or likely registrational endpoint in that study. If so, I'm just wondering if you can point to any precedents that have recent approvals in B cell or large B cell lymphoma that might serve as a model to build this trial after.

Alison Moore, Chief Technical Officer

Hey, Mark, let me take on that question. As Rafael mentioned, ALLO-501A is proceeding as a single-arm pivotal study. In any single-arm study, two important efficacy measures are the response rate or objective response rate, and then the second is the durability of the response. That has been part of the discussion with the FDA, and we expect those two primary and co-primary endpoints to be key measures of efficacy. Safety, of course, is also part of the data review.

Michael Schmidt, Analyst

Okay, super helpful. Thanks for taking the question.

Operator, Operator

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

Reni Benjamin, Analyst

Hey, good afternoon, guys. Thanks for taking the questions. I have two: just going back to the ALLO-647 study, can you talk about it in terms of a randomized study? If that trial fails, how might that impact the entire application of 501A and 647? And if it works, could this generate a general lymphodepletion regimen, potentially even with autologous therapies? And then just something more for Eric about the status update on the development partnerships. One that interests me in particular is Notch and your recent collaboration with Pantheon. When you're striking these relationships, how do you plan to uncover the value, or do you want to keep abreast of it because it's pretty novel new technology? Any update on Overland, the joint venture, if there’s a deliverable this year that we can keep track of? Thanks.

David Chang, President and CEO

You know, all three are great questions. The question about ALLO-647, this is drug co-development, where we have to demonstrate the contribution of 647 to lymphodepletion. We have more than enough data sets coming from both the CD19 501 and 501A programs as well as the multiple myeloma program. Certainly, there is a possibility of study failure, but all the information we have right now makes us confident that the study will demonstrate the contribution of ALLO-647 in a meaningful way. Regarding the potential of using 647 beyond our own setting, we're discussing that internally; how can we best leverage the advantages of 647 in other settings such as autologous therapy. While we're exploring that, our primary focus is optimizing its use. As for the partnerships, I'll ask Eric to respond.

Eric Schmidt, Chief Financial Officer

Thanks, Reni. Your questions about our technology partners: We've formed several relationships that give us access to gene and cell engineering capabilities, including Notch and Pantheon. Specifically with Notch, we're looking at making fully functional T cells from an IPSC source; the partnership is progressing well. Pantheon is new for us, and we’re working with them to enhance our gene engineering capacities, and we see Allogene as a focus project for them. Finally, regarding the joint venture with Overland in China, they are building a manufacturing facility required to commercialize our therapies and are making good progress. We hope to be able to launch that facility later this year. Thank you for the question.

Reni Benjamin, Analyst

Thank you.

Operator, Operator

Thank you. Our next question comes from Luca Issi with RBC. Your line is open.

Luca Issi, Analyst

Oh, great. Thanks so much. Today my question is regarding ALLO-647. Obviously, the FDA is asking you to state the contribution of ALLO-647. Is this something that is limited to non-Hodgkin lymphoma? Or should we expect the FDA may ask you for similar trials for multiple myeloma and solid tumors? And also on business development, we've seen a couple of deals recently where companies have decided to monetize some of their additional manufacturing capabilities to extend their runway, including Uttara, Fuji film, or homology, Oxford. What is your reaction to those deals, and is this something you may consider? Lastly, for CD70, I think I've seen a clinical trial of gov that the size of TRAVERSE increased from 48 patients to 120 patients a couple of weeks back. Do you have any color on that? Thanks so much.

David Chang, President and CEO

Yes, regarding ALLO-647, we see lymphodepletion as an area that's generalizable and extendable to other indications. That is our current position and we have no specific discussions regarding the contribution of ALLO-647 for depletion across indications yet. On manufacturing plans, the short answer is no. We value ownership of the Cell Forge 1 facility absolutely critical for functioning and commercializing across many product opportunities. Given our strong cash position, we don't see a need or interest in monetizing it. As for the TRAVERSE clinical trial's size, I wouldn't read too much into that. The clinical team often adjusts parameters for studies to allow utmost flexibility in execution, and we don’t have plans at this stage to enroll the full cohort you referenced.

Operator, Operator

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

Asthika Goonewardene, Analyst

Hi, guys, thanks for taking the questions. I want to pick on Alison, since she's on the call today, if I may. Alison, a while back, especially, you talked about the goal of the allogeneic cell therapy to get around 1,000 or more batches out of a single donor draw. You had some ways to go to reaching that, and a little while back, you were telling us that you were getting around maybe 100 batches per draw. Where are you on that today? And then also, are you able to incorporate incremental innovations to manufacturing into the production of cell therapies that are already in the clinic, or does that essentially require a lot of new work and even a new IND? Thanks.

Alison Moore, Chief Technical Officer

Thank you. Yes, great question. Our goal at Allogene has been to enable approximately 100 doses from a single luciferase draw. I can say that we know that we can do that, and we have been very successful in optimizing yield. Our focus right now is to ensure supply across all of these programs, and there is definitely potential for improvement in the future. With respect to your question on introducing novel technologies, this relates to the degree of change and how well we understand our product and process. We have been able to introduce exciting new technologies, but we will always do that in collaboration with the agency with the best analytical measures. Focusing on product quality and measuring it is always in our best interest.

Asthika Goonewardene, Analyst

Great. Thanks for the color. I appreciate that.

Operator, Operator

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

John Newman, Analyst

Hey, guys. Thank you for all the information on the call and for taking my question. I was just wondering if you're confident that you can get a patient population in the pivotal study that is representative of patients who are currently receiving autologous therapies? The reason I'm asking is I feel like in some of the most recent updates, you've treated some patients that have already had CD19 therapies and failed them. To get a true picture of the potential of your product, ALLO-501, wouldn’t the agency be curious about what it looks like in a population similar to autologous therapy? Just curious if you're confident you'll be able to do that in a pivotal trial. Thanks.

David Chang, President and CEO

Thanks, John, for the question. It's a great one. In a Phase 1 study, we go through various clinical situations with regard to the kinds of patients that we enroll. One of the questions obviously is what happens to patients who have received CD19 drug therapy, as you mentioned. That doesn't mean that the population we enrolled in the Phase 1 study will be the one in the pivotal study. Those discussions with the FDA will take place. We fully expect our investigators to support us, ensuring that patients will enter the trials with better access to therapies. We have absolutely no doubt this is achievable.

Operator, Operator

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

Raju Prasad, Analyst

Thanks for taking 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 you're looking at before deciding to move the program forward. Just curious to know how much data you need from the nirogacestat program as well as 605 to really make that decision, and how much the potential efficacy improvements of the autologous therapy—focusing on the approval of other therapies play a role in the decision-making process.

Rafael Amado, Executive VP of Research and Development and Chief Medical Officer

Great question. I'll ask Eric to respond to that.

Eric Schmidt, Chief Financial Officer

Thanks for that, Raj. First, we have a strong foundation with what we've shown on ALLO-715. There's a lot of confidence in the results we've presented. While we are trying to build off that with either the combination approach or the ALLO-605 TurboCAR, we are keen on where the bar will be going forward. The results from Johnson & Legend support the efficacy of autologous cell therapy, which highlights the challenge we shall overcome. AS you know, the autologous therapies are unlikely to be applicable to patients who cannot tolerate the waiting time for collection and manufacturing, particularly those who can't tolerate bridging chemotherapy. For those reasons, we see a clean opportunity for our product. We will collect data and move forward with those insights.

Operator, Operator

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

Unidentified Analyst, Analyst

Hi, this is Terry on the line for Jason. Thanks for taking our questions. Two parts: one regarding manufacturing and the other on the broader BCMA development. For in-house manufacturing, are you expecting your in-house capabilities to fully support both the pivotal as well as the commercial demand for 501? And then, does your in-house manufacturing address vector supply, or is that partnered with a third-party manufacturer? Regarding BCMA development, I am wondering if there is potential to start a pivotal trial in the third line setting, given the way that the space is evolving toward earlier lines?

Alison Moore, Chief Technical Officer

I'll take the manufacturing question very quickly. Our facility is designed and built to focus on CAR-T at this time, and the answer is yes; it will have the capacity to supply commercial product for ALLO-501A. Regarding raw materials, we have a broad network of third-party suppliers we work with regularly.

David Chang, President and CEO

Regarding BCMA, these therapies will make their way into earlier lines of therapy, starting in later lines first. Once we make a decision, we will develop a comprehensive program!

Operator, Operator

Thank you. In the interest of time, we can take one more question from Dane Leone with Raymond James. Your line is open.

Dane Leone, Analyst

Thanks for taking the questions. One related question: Do you have an updated view on the impact of prior CD19 therapy like rituximab within the lymphoma program? That's an outstanding question that needs to be discussed since the update of the ALPHA program at ASH. Regarding BCMA, does your team have a view of why or why not prior CD19 or BCMA-targeted therapy might have a potential negative effect on responses to an allogeneic cell therapy product?

David Chang, President and CEO

The data in autologous is actually very telling. Many patients do not respond, particularly if they were refractory or they relapsed relatively quickly. This is something we see in the allogeneic setting. We are not keen on involving these patients going forward. As for BCMA, we have not had much experience, so we can't really answer on parallels but we’re currently focusing on studying BCMA-experienced patients.

Operator, Operator

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

David Chang, President and CEO

Thank you again for joining the call today. Based on our strong execution since inception, coupled with our healthy cash position, and our focused approach to drug development, I believe we remain positioned to transform and lead the field of allogeneic CAR T. We look forward to sharing our continued progress with you throughout the year. Operator, you may now disconnect.

Operator, Operator

Thank you, ladies and gentlemen, for your participation in today's conference. This concludes the program. You may now log off and disconnect.