Good day, ladies and gentlemen, and thank you for standing by. Welcome to Allogene Therapeutics fourth quarter and year-end 2022 earnings conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star one one on your telephone keypad. At this time, please be aware that today's conference call is being recorded. I would now like to turn the call over to Christine Cassiano, Chief Communications Officer. Ms. Cassiano, please go ahead.
Thank you operator, and welcome to our call. Today, after market closed, Allogene issued a press release that provides a business update and financial results for the fourth quarter and full year 2022. This press release and today's webcast are both available on our website. Following our prepared remarks, we will host a Q&A session. We ask you to limit your questions to 1 per person as we will keep this call to an hour and do our best to get to as many as possible. Joining me today are Dr. David Chang, President and Chief Executive Officer, Dr. Zachary Roberts, Executive Vice President of Research and Development, and Dr. Eric Schmidt, Chief Financial Officer. During today's call, we will be making certain forward-looking statements.
These may include statements regarding the success and timing of our ongoing and planned clinical trials, data presentations, regulatory filings, future research and development efforts, manufacturing capabilities, and 2023 financial guidance, among other things. These forward-looking statements are based on current information, assumptions, and expectations that are subject to change. A description of potential risks can be found in our earnings press release and latest SEC disclosure documents. You are cautioned not to place undue reliance on these forward-looking statements, and Allogene disclaims any obligation to update these statements. I'll now turn the call over to David.
Thank you, Christine. Thank you to all who have joined our call. 2023 will mark the 5th year since Allogene's inception. Each year, as our organization has matured, our work takes on a greater and greater importance for the patients we aim to serve. Allogene was conceived shortly after the first autologous CAR T therapies were approved by the FDA. These therapies sparked a new industry and have since advanced to become some of the most potent anti-cancer agents for several types of hematologic malignancies. The clinical success achieved by the autologous cell therapies has also heightened its demand as well as its inherent limitations. As an individualized therapy, the technology is limited by a lack of scalability and timely delivery. Today, it is estimated that one out of 10 patients in the U.S. who are indicated for CAR T therapies are receiving this treatment.
We are now facing a crisis as patient demand far outweighs the ability for autologous therapies to meet the growing need, thereby constraining the growth of this modality and limiting access for patients. Unfortunately for patients, time is not a luxury they can afford. Every day matters when your disease is progressing. We continue to hear from physicians that the complexities and delays in manufacturing are limiting which patients can access CAR T therapy. At Allogene, we have always envisioned a different future for CAR T, one in which cell products can be produced at scale, just on demand and delivered to all patients in need within days. I believe the data we presented at our R&D Showcase late last year demonstrates it is no longer a question of if, but when this vision will become a reality.
As we begin our fifth year, I believe the timeliness of when we will be able to execute on this vision are becoming increasingly CLIA, as evidenced by our ongoing and potentially pivotal Phase II study in large B-cell lymphoma. For those of us immersed in the development of cell therapy, it is easy to get caught up in the minutia of cross-trial clinical data comparisons while losing sight of the fact that what we are developing is fundamentally different from other modalities. In our two most advanced trials, 92% of all enrolled patients receive products with 100% of infused product manufactured and released per product specification. In contrast to autologous cell therapy, patients were able to start treatment within two days of enrollment with no bridging treatment.
Unlike bispecifics, treatment consists of one-time dose, free of the hassle, inconvenience, and cumulative toxicity of chronic treatment that can continue for months on end. AlloCAR T is unique in its ability to provide an off-the-shelf product with one-time administration. True innovation is often met with initial skepticism. Those of us involved in the initial development of autologous CAR T therapy remember the naysayers who said it could not be done. Today, despite its inherent limitations, the therapy some of us played a role in developing at Kite Pharma is considered a groundbreaking therapy for non-Hodgkin's lymphoma and has achieved blockbuster status. The skepticism toward allogeneic CAR T is no different today than what we faced at Kite.
We have our share of critics, even in the face of compelling data that is comparable to the current groundbreaking therapy in non-Hodgkin lymphoma. We also have data that shows an allogeneic CAR T is on the path of competing favorably in multiple myeloma, and early but exciting proof of concept data in solid tumor. While we are fortunate to be leaders in this innovative field, we know the only thing that will quiet the skeptics is execution. Execution on clinical development, execution on manufacturing, execution towards BLA filing and commercialization. Fortunately, we have outstanding talent and other resources to execute on the industry's first Phase 2 potential pivotal trial. It is for that reason I'm especially excited to have next to me, Dr. Zachary Roberts.
As our new Executive Vice President of Research and Development, there's no one I trust more to be on the front lines with investigators as we progress our pipeline and bring in the next era of CAR T products. Someone who first had understand that the urgency and challenge we often embrace is to give back to patients and their loved ones, something they so desperately desire, time. I would now like to invite Zach to provide his perspective on our R&D priorities for the upcoming year.
Thank you, David. Before I talk about specific R&D activity, I'd like to share a few thoughts about why I joined Allogene. I think that when you join an organization, it's an opportunity to bring a fresh perspective and regain sight of forest through the trees. Despite knowing many of my new Allogene colleagues for quite some time and having followed the company since inception, I initially carried an outsider's perspective. When I had the opportunity to join the R&D Showcase last November, I was freshly exposed to everything about Allogene, the professionalism of the leadership team, the engagement of its stakeholders, the passion of its investigators. What really stayed with me on the Uber ride back to the airport was the transformational clinical data that had been shared.
I saw 3 product candidates across three different malignancies generating meaningful clinical results in patients who had few other options, and all of this with an allogeneic cell therapy product. For Allogene to have achieved all this in four years was no small feat and got me very excited about what might be possible for this organization's future. As an oncologist who used to care for these patients and someone who has been working every single day in cell therapy development for most of the last decade, I knew that results like those that were shared at the showcase don't come around very often. Shortly after the showcase, when I was offered the opportunity to join Allogene as the head of R&D, I didn't walk, I ran towards the forest. Now as an insider, let's talk about the trees.
I've now been in Allogene for about two months, and as David has rightly noted, the next critical steps are all about execution. Let's first talk about our CD19 program. I've had the pleasure of spending the last few weeks with many of our trial investigators, and I can share that they are equally excited about our Phase I data, our ongoing Phase II study, and what the availability of AlloCAR T may mean for their patients. We are very proud of the fact that we are the first and only allogeneic CAR T company to generate highly competitive efficacy and durability data in large B-cell lymphoma. Data from the Phase I trials of ALLO-501 and ALLO-501A support the ability of a single administration of an allogeneic CAR T product to generate deep and durable responses that are comparable to those with approved autologous CAR T therapies.
This puts us in a league of our own, and we welcome the responsibility that comes with it. As of our R&D Showcase data cut, the overall response rate and complete response rate was 67% and 58% respectively among the 12 patients treated with the single-dose FCA 90 regimen using Alloy process material. Of patients evaluable at six months who received single-dose FCA 90, the ongoing CR rate was 50%, and all CRs at six months were durable at 12 months. The longest CR ongoing at 26 months. With four patients still awaiting six months follow-up time at the data cut, the lowest possible durable CR rate is 33%, and that would remain solidly in the range established by the approved autologous CAR T cells for non-Hodgkin lymphoma.
What is a standout among our data is that all of the patients treated in our trials received an inspect product, and one could argue that on an intent to treat basis, we have the potential to exceed the efficacy bar established by autologous products. In our CD19 Phase I trials, we demonstrated a manageable safety profile with no observed dose limiting toxicities, severe immune effector cell-associated neurotoxicity syndrome, or any graft versus host disease. We now have clinical trial data that shows that we may be able to offer an off-the-shelf CAR T product that has a favorable safety profile in addition to competitive efficacy that is immediately available to all appropriate patients.
Enrollment has begun in the potentially pivotal Phase II allogeneic CAR T clinical trial, ALPHA2, with ALLO-501A in the EXPAND trial, which is intended to demonstrate the contribution of ALLO-647 to the lymphodepletion regimen, which will be open to enrollment early in the second quarter. We are preparing for a Phase III study in earlier line large B-cell lymphoma, targeting trial initiation in the first half of 2024. Now, moving to BCMA. Just last month, data from the Phase 1 UNIVERSAL trial of ALLO-715 in relapse refractory multiple myeloma was published in Nature Medicine. The corresponding editorial by renowned NCI researchers, Doctors Jennifer Brudno and Jim Kochenderfer, reinforced what we've known to be true. The UNIVERSAL study has demonstrated that an off-the-shelf CAR T treatment is feasible in myeloma. Let me quote from their editorial specifically as it relates to ALLO-715.
Quote, "Its development drives the field forward on the road to more effective off-the-shelf cellular therapies." End quote. We are proud that ALLO-715 is the first allogeneic anti-BCMA CAR T to demonstrate proof of concept in multiple myeloma with response rates that are similar to an approved autologous CAR T therapy. The most recent data we presented on ALLO-715 at ASH in December demonstrated substantial and durable responses. Through a median follow-up of 14.8 months as of the October 11th, 2022 data cutoff, the overall response rate was 67% in the SCA 60 cohort, and the very good partial response or better rate was 42%. All VGPR or better responses were minimal residual disease negative. The median duration of response was 9.2 months, with the longest ongoing response at 24 months.
Important to this patient population, none of the patients received bridging therapy, and patients initiated lymphodepletion as early as zero days from enrollment and with a median of five days from enrollment. The safety profile of ALLO-715 was manageable with low grade and reversible neurotoxicity and no GVHD. Eight patients or 29% experienced Grade 3 or higher infections, and eight patients experienced prolonged Grade 3 or higher cytopenias. While we remain very excited about what ALLO-715 has shown in the clinic, we also do recognize that the bar for efficacy in multiple myeloma is high in patients who are able to receive autologous CAR T-cells. As we assess all of our options for our BCMA program, we are evaluating manufacturing process improvements across our BCMA candidates, ALLO-715 and ALLO-605, to achieve optimal performance.
Through our work in hematologic malignancies, we've established proof of concept for our platform, including a proprietary approach to lymphodepletion using ALLO-647 to create a window for cell expansion and persistence. This is just the beginning. Our strategy in solid tumors is to start with a target in CD70 that bridges both heme and solid tumors in order to establish proof of concept. ALLO-316 is being evaluated in TRAVERSE, a Phase I study of patients with relapse refractory renal cell carcinoma. In RCC, standard of care includes two main classes of therapies, TKIs, or tyrosine kinase inhibitors, and immune checkpoint inhibitors. Once patients have been exposed to drugs in each of these classes, there are a few remaining options. One recent benchmark is data from the pivotal tivozanib trial in third line RCC.
The objective response rate was less than 20% in this study, and the median progression-free survival was less than six months. These data highlight the profound unmet medical need in advanced stage renal cell carcinoma. Initial data from our TRAVERSE study demonstrated promising anticancer activity in the subset of nine patients with confirmed CD70 positive RCC. As of the data extract date, the disease control rate was 100%, including three patients who achieved a partial response with the longest response lasting until month eight. While early, it is exciting to see this type of activity in a dose escalation Phase I trial. Across 17 patients treated, the safety profile was generally manageable with no GVHD. One dose-limiting toxicity of Grade 3 autoimmune hepatitis occurred in the second dose level, and enrollment has been expanded in that cohort.
Grade three or higher prolonged cytopenia was observed in three patients. CRS was low grade with the exception of one case of grade three CRS. Neurotoxicity was also low grade, reversible, and seen in only three patients. The data that we've shared suggests that patients who have measurable CD70 expression tend to do better in terms of response than those who have absent or unknown levels of CD70. We are now deploying a new investigational in vitro companion diagnostic assay designed to prospectively assess CD70 expression levels to enhance patient selection. In the TRAVERSE trial, we plan to complete dose exploration and initiate expansion cohort enrollment in 2023. We may also investigate ALLO-316 for other CD70 expressing solid tumors and hematologic indications, or in combination with other anticancer therapies such as immune checkpoint inhibitors.
Our CD70 Phase I data set was also notable for the high levels of CAR T-cell expansion and persistence that were observed in the study. We believe that this may relate to the use of a novel anti-rejection technology that we call Dagger. This technology is designed to enable AlloCAR T-cells to resist rejection by the host immune cells, enabling a prolonged window of persistence during which AlloCAR T-cells can expand and actively target and destroy cancer cells. The Dagger platform arms AlloCAR T-cells with a CD70-targeting receptor designed to recognize and deplete alloreactive CD70-positive host T-cells while also masking the CD70 molecule expressed on the AlloCAR T-cells themselves, thus preventing the AlloCAR T-cells from killing one another in a phenomenon known as fratricide.
As presented at the forefront of cancer immunotherapy Keystone Symposia, preclinical data indicate that DAG- CD70 Dagger CAR T-cells can be combined with other anti-tumor CARs in a single cell, providing both protection from allo rejection and dual specificity killing capability, thus offering a differentiated next generation product candidate profile. As we progress our pivotal trials, every one of us in Allogene are keenly aware that this is what we came to do, get products approved for patients who desperately need them. This is our opportunity. We have everything that we need to make this happen, and nothing is more exciting than executing on what others might consider to be the daunting challenge of creating an innovative new therapeutic modality. I will now turn the call over to Eric.
Thank you, Zach. Let me start by saying something that may be obvious to those of you who have already had the pleasure of meeting Zach, and is certainly evident to those of us who have been working with Zach on a daily basis for the past two months.
Zach's ability to see the forest is represented by the full breadth of our advancing pipeline that has brought an infectious enthusiasm to Allogene. At the same time, his ability to help navigate paths forward through the trees has been inspirational to our research and development team. I am confident that those of you who have yet to meet Zach will be as excited about what he brings to Allogene as we are. Turning to our finances, as we all weather what continues to be a challenging market, especially for small and mid-cap biotechnology companies, we are very proud of how our team is adjusting and responding to this challenge. We appreciate that having a strong balance sheet is critical to our ability to deliver shareholder value.
As you may have been able to discern from the comments by David and Zach, one of the critical elements of our corporate and financial strategy is to efficiently deploy our capital resources to support key programs toward value-creating milestones. To that end, we continue to evaluate all opportunities to best move our pipeline forward with a focus on our highest potential candidates. We remain very fortunate to be in a strong financial position, ending the year with $576 million in cash equivalents and investments and no debt. In 2023, we will continue to take important measures designed to prolong our cash runway. In order to achieve this, we are focusing on our most critical activities, including nomber one , executing on our Phase II CD19 pivotal trials. Number two, evaluating the best path forward for multiple myeloma.
Number three, continuing to progress our ALLO-316 trial in solid tumors. We strongly believe we have the operational capabilities, scientific insight, and capital resources needed to succeed in these endeavors. The company expects a decrease in cash equivalents, and investments of approximately $250 million in 2023. Based on current expectation, the company expects the cash runway will be sufficient to fund operations into 2025. We expect our full year 2023 GAAP operating expenses to be approximately $350 million, which includes estimated non-cash stock-based compensation expense of approximately $90 million. This guidance excludes any impact from potential business development activities.
Turning to 2022 financials, research and development expenses were $75.4 million for the fourth quarter, which includes $7.4 million of non-cash stock-based compensation expense, with full year expenses of $256.4 million, which includes $42.5 million in expenses associated with non-cash stock-based compensation. General and administrative expenses were $21 million for the fourth quarter of 2022, which includes $9.8 million of non-cash stock-based compensation expense and $79.3 million for the full year, which includes $41.1 million of non-cash stock-based compensation expense. For the full year of 2022, our net loss was $332.6 million or $2.32 per share, including non-cash stock-based compensation expense of $83.6 million.
With that, we will now open the call for your questions.
Ladies and gentlemen, if you have a question or comment at this time, please press star one one on your telephone keypad. In order to answer as many people's questions as possible, we ask that you please limit yourself to one question. If you have additional questions, feel free to reenter the queue if we have enough time. Again, if you have a question or comment, please press star one one on your telephone keypad. Our first question or comment comes from the line of Michael Yee from Jefferies. Standby. Mr. Yee, your line is open.
Hi, good afternoon. This is Jenna on for Mike. Thanks for taking our question. We wanted to catch up on CD19. What are you seeing in terms of the enrollment for the pivotal trial? Do you have any feedback to share from investigators? Just real quick on multiple myeloma, do you have any latest thinking on the franchise? When might we see some data from the TurboCAR program? Thank you.
Hi, Jenna. This is David Chang. I'm gonna pass the question to Zach. Going with the spirit of one question, you know, we will just answer the first question.
Thanks, David. The enrollment in the ALPHA2 study is continuing according to plan. We are continuing to expand the number of sites that are open to enrollment, and we'll be expanding outside of the U.S. into additional geographies over the course of the year. As far as investigator feedback goes, I recently had an opportunity to catch up with several investigators at the Tandem meeting in Orlando, and enthusiasm is extremely high for the trial in general and for enrollment.
Thank you. Our next question or comment comes from the line of Tyler Van Buren from Goldman Sachs. I mean, from Cowen. Mr. Van Buren, your line is open.
Hey there, guys. Thanks very much for taking the question. Given the prioritization of the earlier line large B-cell lymphoma trial for ALLO-501A, can you elaborate on the rationale behind that decision and discuss the potential design and timeline of the trial? In particular, I'm curious to know if it's expected to be identical to the Yescarta second-line ZUMA-7 trial or if there might be some differences?
Hi, Tyler. I for a second thought that you had moved your position to Goldman. In terms of, you know, how we are thinking about the earlier line, I mean, obviously we see this as an opportunity. You know, we have a very compelling data in the.
2+ lines where we are already doing a pivotal study. You know, in terms of, you know, what, you know, what is the sweet spot, you know, to which we can sort of advance the program to the earlier line, that's very much in discussion. What you're referring to as a transplant-eligible, you know, large B-cell lymphoma, obviously, that is one of the opportunities, but we are also exploring a different path towards, maybe a different population or maybe even to an earlier line.
Thank you. Our next question or comment comes from the line of Salveen Richter from Goldman Sachs. Mr. Richter, your line is open.
Hello, this is Anami on for Salveen Richter. On the potentially pivotal trial in multiple myeloma, where do you stand on regulatory discussions? I guess whether that trial would be pivotal. Could you also comment on transitioning to cells for June? Thank you for taking our question.
All right. Let me take that question, and I'm just gonna answer the multiple myeloma question. In terms of multiple myeloma, you know, before going into that, you know, 2023 for us is really the year of focus. Where we are putting all our attention is, you know, ALLO-501A ALPHA2 study, you know, based on the compelling data we have and also the study that we are conducting as potentially a pivotal study. For all the obvious reasons, our priority is the ALPHA2 study. Along with that, as we have just talked about, you know, moving the program to the earlier lines, that becomes another important option, you know, that we wanna exercise as early as possible.
You know, we'll be talking about the study design with the investigators and hopefully if all goes well, you know, potentially start the earlier line study by, you know, 2024. That brings to your question about the multiple myeloma. Where we stand right now is that given the need for us to prioritize, we gonna, you know, we are thinking that, you know, the potential pivotal study for the multiple myeloma will not be 2023.
It will be pushed out to more likely 2024, during which time, you know, we will continue to engage the regulatory bodies for potential feedback, as well as looking at the manufacturing process in order to make sure that, you know, we can optimize the process best we can across different assets that we have, whether it's 715 or ALLO- 605.
Thank you. Our next question or comment comes from the line of Brian Cheng from JP Morgan. Mr. Cheng, your line is now open.
Hey, David and team. Thanks for taking my question. It's good to see that you're on track to complete enrollment for ALPHA2 in the first half of 2024. Do you need some patients to be dosed with the Allo process, manufacturing process before filing for approval? Any updates on getting the Allo process in? Thank you.
Hi, Brian. I'm gonna ask Zach to respond to your question.
Hey, Brian. The Alloy X process.
I think his question was Alloy process.
The Alloy process. Yeah, sorry about that. I got confused. Yes, the Alloy process is the process that we're taking forward in both of the pivotal trials for ALLO-501A. This is the manufacturing process that we discussed at length at the RDS, and you know, the one that we believe is the most appropriate to take forward into the pivotal study. All of the patients dosed in both EXPAND and ALPHA2 will be dosed with the Alloy process. Sorry about that.
Thank you. Our next question or comment comes from the line of Mark Breitenbach from Oppenheimer. Mr. Breitenbach, your line is open.
Hey, guys. Thanks for taking the question. I have a question on the Dagger platform, actually. I guess I'm wondering if this is something that's gonna be mostly reserved for solid tumor programs or if this could be eventually deployed across, you know, the entire pipeline. Kind of what are its limits in your view? Is this something that is going to supersede the TurboCAR approach or maybe even supersede lymphodepletion as we think about it today, given what we've seen so far from the TRAVERSE study? Any comments you can offer would be appreciated. Thank you.
Thanks very much for that question. It's an excellent one, and I think it really defines how we're thinking about Dagger. As you rightly point out, the expansion data that we saw in the early data from the TRAVERSE study do support that there is a mechanism by which the Dagger technology is promoting the expansion and persistence of these cells. Additionally, we recently shared preclinical data showing that when we combine a CD70 CAR that possesses the Dagger capability with other antitumor CARs such as CD19, we actually do see the benefit of both the killing of the allo-reactive host T-cells, but also enhancement of the killing activity of the CAR in general by including dual targeting capability.
I think that we consider these as hints as the potential expansion of this Dagger technology into additional CAR T products going forward. Now, whether this will replace the Turbo approach or not, I think that these two technologies are complementary, and we are doing lots of work both in the clinic as well as preclinically to try to explore where these two technologies may be deployed, and both in solid tumors.
Thank you. Our next question or comment comes from the line of Michael Schmidt from Guggenheim Partners. Mr. Schmidt, your line is open.
Hey, this is Paul on for Michael. Thanks for taking our question. Just one on 501A. How are you currently thinking about the ex-U.S. opportunity for the program? What do you need to see to opt into the ex-US rights for 501A? Thank you.
Yeah, I'll take that. This is Eric. Thanks for the question. As you know, historically, Servier had held the ex-U.S. rights, and we were co-developing the product, ALLO-5 01A with Servier on a global basis. As of September of last year, Servier opted out of that co-development plan and provided us the option to opt into the ex-U.S. rights. We have yet to pick up that option, we believe that we have the potential to pick up that option in the future. Our decision whether we exercise the option or not will obviously be based on a number of factors, some financial, some developmental. You know, stay tuned. We hope to provide you with an update on that in the future.
Thank you. Our next question or comment comes from the line of John Newman from Canaccord Genuity. Mr. Newman, your line is open.
Hi there, guys. Thanks for taking my question. Just had a question about the patient enrollment for the pivotal studies for ALLO-501. Just wondered if you could talk about some of the ways that you are ensuring that you're getting sort of patients that are optimally suited for CAR T treatment. I think there's some concern, not a whole lot, that some physicians may sort of, for whatever reason, not wanna put patients that they would normally put on autologous therapy on your treatment. Also, I noticed in the press release, patients may receive treatment in the outpatient setting at the investigator's discretion.
Just curious if you can talk about exactly how that's gonna be different, if it's gonna be sort of full outpatient or, sort of a, or a combination between what we think of as outpatient and inpatient. Thanks.
Hey, John, this is Zach again. I'll take the second question first about outpatient. You know, one of the things that we've benefited from is quite a lot of experience out there in the investigator community in dosing patients with autologous CAR T-cells in an outpatient setting. A lot of the infrastructure that is required to safely handle this and for bone marrow transplant, for that matter, has already been established. Our investigators, you know, on a patient-by-patient basis are enthusiastic about potentially leveraging the existing infrastructure that they have built for autologous therapies for our trial as well. As far as the first question goes, I think investigators know very well which patients are best suited for CAR T-cells in general.
you know, our products have quite a number of benefits compared to autologous products that we've gone into great detail about previously. That said, the investigators do know that not, you know, that they're not selecting patients that would not be eligible for autologous CAR T-cells for our trial. That is universally not the case. They know very well which patients are likely to derive benefit from this modality, and they choose those patients appropriately.
Thank you. Our next question or comment comes from the line of Reni Benjamin from JMP Securities. Benjamin, your line is open.
Hey, great. Thanks, guys. Thanks for taking the questions. I'd love to just get some more color on the manufacturing tweaks that are taking place, you know, especially for like ALLO-605 and ALLO-715. You know, Is it just about switching that process to the Alloy process, or is it a completely different process, sort of like soup to nuts? When do you think, you know, you might actually start resuming enrollments with the new process?
Reni, let me take that question. What we have learned over the years is, as we've been saying all along, manufacturing process makes a big difference. As we gather, not just, you know, the information from the manufactured products, you know, we do have benefits of having taken those products into the clinics. This is really the, you know, opportunity to interrogate not just the clinical data, but the translational data to really understand how the manufacturing, you know, plays out when the product goes into the clinics. That is sort of fund of the knowledge that we have. Our process development team is using that knowledge to improve the manufacturing process and trying to optimize the product, beyond, you know, what we have already done with the Alloy process.
With the, you know, the focus on, you know, right now is really, you know, as Zach had mentioned in his prepared statement, you know, on the ALLO-605 and ALLO-715. For the timeline of reintroducing those products back into the clinics, we are probably looking at sometime in 2024.
Thank you. Our next question or comment comes from the line of Luca Issi from RBC Capital Markets. Issi, your line is open.
Oh, great. Thanks so much for taking our question. Congrats on the progress. Just a quick one, maybe on CD19. How should we think about timing of actually data readout for the pivotal for CD19? Obviously, the single arm trial is larger but has ORR as primary endpoint, while the randomized trial is smaller but has PFS as primary endpoint, which will take longer time to read out. How will these factors offset each other? Would it be fair for us to assume that both trials will read out in early 2025? Thanks so much.
What we've guided to is completion of enrollment in the first half of 2024. and as far as data availability goes, we are targeting to have data available for both ALPHA2 and EXPAND at roughly the same time.
Thank you. Our next question or comment comes from the line of Asthika Goonewardene from Truist. Ms. Goonewardene, your line is open.
Hi, guys. Asthika Goonewardene from Truist here. Thanks for taking my question. Just want to go back on the BCMA program quick and just want to confirm that the manufacturing optimization of six oh five is still ongoing. Related to that, to make the decision to choose which of these products you may want to actually take in a pivotal study, we've seen some data with seven one five. Haven't seen ALLO-605. David and team, just want to know about how many patients worth of data would you want to see with this now optimized six oh five before you make that decision? Thank you.
You know, many layers of questions there. You know, let me first start with the ALLO-605. I mean, we have treated very small number of patients. As we have previously stated back in November of last year, we already started looking at the manufacturing process of ALLO-605. Now, as Zach had said, you know, we are also reviewing, since we're not moving forward with the ALLO-715 program into the pivotal for, you know, prioritization reasons, we have an opportunity to sort of further review the manufacturing process of ALLO-715. In a way, you know, we are looking at the manufacturing process of both ALLO-715 and ALLO-605 concurrently, to come up with what we believe is more of an optimal manufacturing process.
You know, the process optimization is exactly what we are talking about. As I said, we are probably looking at sometime in 2024 to reintroduce products back into the clinic. In terms of whether we will go with both or choose one, I think that's a little bit too early, stay tuned.
Thank you. Our next question or comment comes from the line of Jack Allen from RW Baird. Mr. Allen, your line is open.
Great. Thank you so much for taking the questions and congratulations to the team on the progress. I know there's been a lot of discussion about the longer-term catalyst surrounding Allogene, but I was hoping you could dive a little bit more into what we should expect throughout the course of 2023. Do you expect to provide updated data from the CD19 program and any additional comments on the Alloy manufacturing process? Any thoughts there would be great. Thanks so much.
Jack, it's Eric. Thanks for your question. Yes, we do intend to present updated data sets on both our CD19 programs as well as our CD70 program and renal cell carcinoma. Those would be the anticipated updates that we've already signed up for. There could be additional updates from other programs if and when we choose, but those are the two milestones I want you to have at the top of your list. Certainly, as we go through the course of the year, there could be other updates as well, including on the Alloy manufacturing process and the improvements we're making to the BCMA programs.
Thank you. Our next question or comment comes from the line of Kalpit Patel from B. Riley Financials. Mr. Patel, your line is now open.
Yeah. Hi, thanks for taking the question. Just one follow-up on the BCMA manufacturing process improvements. I guess, does the process improvements imply that you're not enrolling any more patients into the ALLO-605 trial or is that still ongoing?
Kalpit, we actually said back at the R&D Showcase in November that we had paused enrollment in the ALLO-605 study as we work toward an improved manufacturing process for that construct. That is correct. We are not currently enrolling in the ALLO-605 Phase I study.
Thank you. Our next question or comment comes from the line of David Dai from SMBC. Mr. Dai, your line is now open.
Yeah. Thank you for taking my questions. I have a question on ALLO- 316 using CAR T. Could you perhaps shed some additional color on the CD expression profile of these CD70 positive patients? What's the CD70 density and tissue expression of these CD70 positive patients, and are we seeing correlation of these profiles with the depth of response?
David, this is David Chang. You know, you were breaking up a little bit, but I think the question was centered around CD70 expression in ALLO-316 program. In the R&D Showcase, we, you know, highlighted approximately 15 patients that we have treated to date with the ALLO-316 program. What we have seen was CD70 expression does make a big difference. And the responses that we have seen, there were three out of 9 patients who have achieved a objective tumor response. All those cases occurred in the CD70 positive population. We are also looking at the level of CD70 expression to, you know, further optimize the patient selection, but that is an ongoing process.
Thank you. Our next question or comment comes from the line of Jason Gerberry from Bank of America. Mr. Gerberry, your line is now open.
Hey, guys. Thanks for taking my questions. I wanted to, maybe David, just get your thoughts on the Galapagos point-of-care manufacturing model, just as a competitive, I guess approach, you know, given, you know, your key to the value proposition, you know, for ALLO-501A is the shortening of the vein of any time. They claim to kind of have a seven-day, you know, period. Ultimately, there's, like, two to five days that may transpire between getting ALLO-501A ultimately from time of treatment decisions. Overall, just maybe less curious to get your perspective on that as a competitive approach.
For my, for my follow-up, just on the BCMA update, just given the likely shift to earlier lines here with the KarMMa-3 and CARTITUDE-4 updates, you know, that's going to make for just an elevated bar and changing landscape. You know, as you guys think about longer term, you know, reentering the competitive mix, you know, is it an elevated bar ultimately? I'm just kind of curious how you guys think about sort of the evolution into earlier lines and how that'll play into your future development.
You know, two questions there. You know, let me take the Galapagos as well as the, you know, the point-of-care manufacturing. You know, when, you know, I was at Kite, as we're looking at the future of cell therapy, I mean, certainly, the ease of autologous manufacturing, which there were many opportunities, could play a role. You know, when we sort of think about from the allogeneic angle, the benefit that allogeneic product provides is more than just being to vein time. You're talking about patients not having to undergo leukapheresis, not having to be, you know, very, you know, carefully subjected to the, you know, the manufacturing slot availability and leukapheresis slot availability.
Also, you know, manufacture product and meeting the specification, you know, which as we have learned, you know, as more and more autologous CAR T products are coming online, you know, all these things, you know, does play a role. Also, you know, I think, you know, nowadays everybody's aware the lentiviral, you know, availability that also plays a role in the manufacturing of the, you know, CAR T. In our case, manufacturing of one lot allows treatment of many patients. Yes, you know, it's great to see the progress being made in, you know, sort of different ways of manufacturing autologous CAR T. I think the allogeneic benefits still far outweighs what the autologous manufacturing can do, even with the point-of-care manufacturing.
You know, the BCMA with early alliance, I'm gonna ask that question as well. You know, right now, I think the BCMA autologous CAR T, the main problem is that of access. I mean, the access problem will not go away near term. We believe that the profile that we have with 715, if we can even, you know, slightly improve the response rate, you know, beyond what we already have, and we already have the durability that's matching up with one of the approved autologous CAR T products, I think we will remain quite competitive in the BCMA space.
Thank you. Our next question or comment comes from the line of Raju Prasad from William Blair. Mr. Prasad, your line is now open.
Thanks for taking the question. On the 316 program, you know, you mentioned CD70 levels and the potential for going into liquid tumors. Just wonder if you provide a little more color on that? I think there was a paper recently on kind of EGFR relapse patients showing CD70 positive, or CD70 as a marker. Just kind of curious your thoughts on that as well, and if that's kind of crossed your plate as far as potential indications to look at. Thanks.
Thanks, Raju, for the question. You know, CD70, we think is a great target for a number of reasons, including its wide distribution on a number of different malignancies. You know, we think of this really in terms of solid tumors versus heme malignancy. We picked RCC because its prevalence of CD70 expression is very high. As you pointed out, I think, the field is learning more and more about additional solid tumors and subsets thereof, where CD70 may also be expressed. You know, of course, we saw that same report that you did and are looking into that carefully. On the heme malignancy side, you know, obviously T-cell malignancies, lymphomas, and leukemias are well described as having high expression of CD70.
It's also found on myeloid malignancies like AML and also, in diffuse large B-cell lymphoma, a substantial fraction of those patients express CD70. I think there's a lot of options for us as we continue to execute in the renal cell carcinoma space, for us to consider expanding in additional avenues.
Thank you. Our next question or comment comes from the line of Tony Butler from EF Hutton Group. Mr. Butler, your line is now open.
Hi, can you hear me?
Yes, sir.
Yes, we can.
Please go ahead, Mr. Butler.
Thank you. Sorry for the confusion. This is about CD70. I wonder, you know, what you can share with us about the current status of the assay development, you know, whether it's, you know, internal validation versus getting validation from CLIA, the potential timing of when you hope to be able to deploy this for patient selection and whether the next CD70 program update will contain any of the possible number of patients who have been prospectively selected for expression.
This is David Chang. Let me just answer the question about the status of the diagnostic assay. You know, we have developed and validated diagnostic assay to be used in the renal cell carcinoma patients. In fact, the assay has already been deployed to select the patients in the ALLO-316 study. As is the case with any kind of in vitro diagnostic assay that's being used for patients in different indications, additional, you know, validation has to be done. All those work are ongoing. As I said, you know, as Zach has said, you know, the CD70 program, we have many different opportunities, it remains as one of the most exciting programs that we're dealing with right now.
Thank you. I'm showing no additional questions in the queue at this time. I would like to turn the conference back over to management for any additional comments.
Thank you again for joining the call today. We can tell, you know, from all of this call, you know, we are most enthused about the opportunity before us. We are excited about the role we are playing to change the future of CAR T for patients and open up the floodgates to access. We look forward to sharing our continued progress with you throughout the year. Operator, you may now disconnect.
Thank you. Ladies and gentlemen, thank you for your participation in today's conference. This does conclude the program. You may now log off and disconnect.