Earnings Call Transcript - ALLO Q4 2022

Operator, Operator

Good day, everyone, and thank you for being here. Welcome to Allogene Therapeutics' Fourth Quarter and Year-End 2022 Earnings Conference Call. I would now like to turn the call over to Christine Cassiano, Chief Communications Officer. Please go ahead, Ms. Cassiano.

Christine Cassiano, Chief Communications Officer

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 one 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.

David Chang, President and CEO

Thank you, Christine, and thank you to all who have joined our call. 2023 will mark the fifth 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 anticancer agents for several types of hematologic malignancies. But 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 timing delivery. Today, it is estimated that 1 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 needs, 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. Yet 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 who need them 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. And as we begin our fifth year, I believe the timeliness of when we will be able to execute on this vision is becoming increasingly clear, 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 minutiae 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 received products with 100% of infused products manufactured and released for product specification. In contrast to autologous cell therapy, patients were able to start treatment within two days of enrollment, with most reaching treatment quickly. And unlike bispecifics, treatment consists of a 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. But today, despite its inherent limitations, the therapies some of us played a role in developing at Kite Pharma are considered groundbreaking for non-Hodgkin lymphoma and have achieved blockbuster status. The skepticism towards 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, an early but exciting proof-of-concept data in the pipeline. 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 for its BLA filing and commercialization. Fortunately, we have outstanding talent and resources to execute on the industry's first Phase II potential pivotal trial. And 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 is no one I trust more to be on the frontlines with investigators, as we progress our pipeline and bring in the next era of CAR-T products. And someone who understands 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.

Zachary Roberts, Executive Vice President of Research and Development

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 the forest through the trees. So 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. But what really stayed with me on the Uber ride back to the airport was the transformational clinical data that had been shared. I saw three 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. So now as an insider, let's talk about the trees. I've now been at 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 cuts, the overall response rate and complete response rate was 57% and 58%, respectively, among the 12 patients treated with a single-dose FCA90 regimen using Alloy process material. Of patients evaluable at six months who received single-dose FCA90, 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's lymphoma. What is standout among our data is that all of the patients treated in our trials received an inspected 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. So we now have clinical trial data that shows that we may be able to offer an off-the-shelf CAR T product that adds 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 I universal trial of ALLO-715 in relapsed/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; 'its development drives the field forward on the road to more effective off-the-shelf cellular therapies.' 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 11, 2022 data cutoff, the overall response rate was 67% in the FCA60 cohort, and the very good partial response or better rate was 42%. All the GPR 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 0 days from enrollment and with a median of 5 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. But this is just the beginning. Our strategy in solid tumors is to start with a target in CD70 that bridges both hematologic and solid tumors in order to establish proof of concept. ALLO-316 is being evaluated in TRAVERSE, a Phase I study of patients with relapsed/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 6 months. These data highlight the profound unmet medical need in advanced stage renal cell cancer. Initial data from our TRAVERSE study demonstrated promising anticancer activity in the subset of nine patients with confirmed CD70-positive RCC. As of the latest, 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 3 or higher prolonged cytopenia was observed in three patients. CRS was low grade with the exception of one case of Grade 3 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. So 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 dataset 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 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 all CAR 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, thereby 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 DAK-CD70 Dagger CAR T cells can be combined with other antitumor CARs in a single cell, providing both protection from allorejection and dual specificity killing capability, thus offering a differentiated next-generation product candidate profile. As we progress our pivotal trials, every one of us at 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.

Eric Schmidt, Chief Financial Officer

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 for 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 pipeline that has brought an infectious enthusiasm to Allogene. And at the same time, his ability to help navigate paths forward through the trees has been inspirational to our research and development team. I'm 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, 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 #1, executing on our Phase II CD19 pivotal trials; #2, evaluating the best path forward for multiple myeloma; and #3, 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, cash equivalents, and investments of approximately $250 million in 2023. Based on current expectations, 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 noncash 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 noncash stock-based compensation expense, with full year expenses of $256.4 million, which includes $42.5 million in expenses associated with noncash stock-based compensation. General and administrative expenses were $21 million for the fourth quarter of 2022, which includes $9.8 million of noncash stock-based compensation expense, and $79.3 million for the full year, which includes $41.1 million of noncash stock-based compensation expense. For the full year of 2022, our net loss was $332.6 million or $2.32 per share, including noncash stock-based compensation expense of $83.6 million. With that, we will now open the call for your questions.

Operator, Operator

Our first question or comment comes from Michael Yee from Jefferies. Mr. Yee, your line is open.

Jenna Li, Analyst

This is Jenna on for Mike. We wanted to catch up on CD19. What are you seeing in terms of the enrollment for the pivotal trial? And do you have any feedback to share from investigators? And just real quick on multiple myeloma, do you have any latest thinking on the franchise and when might we see some data from the Turbo CAR program?

David Chang, President and CEO

Hi Jenna, this is David Chang. I'm going to pass the question to Zach and going with the spirit of one question, we will just answer the first question.

Zachary Roberts, Executive Vice President of Research and Development

Thanks, David. So 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.

Operator, Operator

Our next question or comment comes from the line of Tyler Van Buren from Cowen.

Tyler Van Buren, Analyst

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?

David Chang, President and CEO

Hi Tyler. For a second thought that you had moved your position to Goldman. In terms of how we are thinking about the earlier line, I mean, obviously, we see this as an opportunity. We have very compelling data in the two-plus lines, where we are already doing a pivotal study. And in terms of what is the sweet spot 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 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.

Operator, Operator

Our next question or comment comes from the line of Salveen Richter from Goldman Sachs.

Unidentified Analyst, Analyst

This is on for Salveen. On the potentially pivotal trial in multiple myeloma, where do you stand on regulatory discussions? And I guess whether that trial would be pivotal? And then could you also comment on transitioning to ?

David Chang, President and CEO

Let me address your question regarding multiple myeloma. For us, 2023 is a year of focus, particularly on the ALLO-501A ALPHA2 study, which we believe has compelling data and could be a pivotal study. Therefore, our main priority is the ALPHA2 study. Additionally, we are looking to move the program into earlier treatment lines as soon as possible. We plan to discuss the study design with the investigators and, if everything proceeds smoothly, aim to start the earlier line study by 2024. Regarding multiple myeloma, we have decided to prioritize our efforts, which means that the potential pivotal study for this indication will likely be postponed to 2024. During this time, we will continue engaging with regulatory bodies for feedback and will also focus on optimizing our manufacturing processes across our assets, including 715 and ALLO-605.

Operator, Operator

Our next question comment comes from the line of Brian Cheng from JPMorgan.

Brian Cheng, Analyst

It's good to see that you're on track to complete enrollment for ALPHA2 in the first half of '24. Do you need some patients to be dosed with the Alloy process manufacturing process before filing for approval? And any updates on getting the Alloy process in?

David Chang, President and CEO

Brian, I'm going to ask Zach to respond to your question.

Zachary Roberts, Executive Vice President of Research and Development

Brian, so the Alloy is currently...

David Chang, President and CEO

I think his question was alloy process.

Zachary Roberts, Executive Vice President of Research and Development

The alloy process is what we are advancing in both pivotal trials for ALLO-501A. This manufacturing method has been thoroughly discussed at the RDS and we believe it is the best option for the pivotal study. Therefore, all patients participating in both EXPAND and ALPHA2 will be treated using the alloy process.

Operator, Operator

Our next question or comment comes from the line of Mark Breidenbach from Oppenheimer.

Mark Breidenbach, Analyst

I have a question on the Dagger platform actually. I guess I'm wondering if this is something that's going to be mostly reserved for solid tumor programs or if this could be eventually deployed across the entire pipeline? And kind of what are its limits in your view? Is this something that is going to supersede the Turbo CAR 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?

Zachary Roberts, Executive Vice President of Research and Development

Thank you for that question. It's a great one and it really captures our perspective on Dagger. The initial data from the TRAVERSE study indicates that the Dagger technology supports the expansion and longevity of these cells. Moreover, we've recently presented preclinical data showing that when we integrate a CD70 CAR with Dagger capabilities alongside other antitumor CARs like CD19, we observe enhanced effectiveness in killing both alloreactive host T cells and improving the overall activity of the CAR through dual targeting. We see these findings as promising indicators for the potential application of Dagger technology in more CAR T products in the future. As for whether this will replace the Turbo approach, we believe the two technologies can complement each other, and we are conducting extensive work in both clinical and preclinical settings to identify the best applications for these technologies in treating both hematologic and solid tumors.

Operator, Operator

Our next question or comment comes from the line of Michael Schmidt from Guggenheim Partners.

Paul Jeng, Analyst

This is Paul on for Michael. Just one on 501A. How are you currently thinking about the ex U.S. opportunity for the program? And then what do you need to see to opt into the ex-U.S. rights for 501A?

Eric Schmidt, Chief Financial Officer

Yes, 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 of ALLO-501A 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, and we believe that we have the potential to pick up that option in the future. Our decision and whether we exercise the option or not will obviously be based on a number of factors, some financials, some developmental. So stay tuned. We hope to provide you with an update on that in the future.

Operator, Operator

Our next question or comment comes from the line of John Newman from Canaccord Genuity.

John Newman, Analyst

I have a question regarding patient enrollment for the pivotal studies for 501. Could you elaborate on how you are ensuring that you are selecting patients who are ideally suited for CAR-T treatment? There seems to be some concern that certain physicians might hesitate to enroll patients who would typically qualify for autologous therapy. Additionally, I noticed in the press release that patients could receive treatment in an outpatient setting at the investigator's discretion. Could you clarify how this will differ, whether it will be entirely outpatient or a mix of what we consider outpatient and inpatient care?

Zachary Roberts, Executive Vice President of Research and Development

John, this is Zach again. So I'll take the second question first about outpatients. So 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. And so a lot of the infrastructure that is required to see if we handle this and for bone marrow transplant for that matter, has already been established. So our investigators 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. And then as far as the first question goes, I think investigators know very well which patients are best suited for CAR T cells in general. And our products have quite a number of benefits compared to autologous products that we've gone into great detail about previously. But that said, the investigators do 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.

Operator, Operator

Our next question comment comes from the line of Reni Benjamin from JMP Securities.

Reni Benjamin, Analyst

I'd love to just get some more color on the manufacturing tweaks that are taking place, especially for like 605 and 715. Is it just about switching that process to the Alloy process, or is it a completely different process sort of like soup to nuts? And when do you think you might actually start resuming enrollment with the new process?

David Chang, President and CEO

What we have learned over the years is that the manufacturing process significantly impacts our results. As we collect data from the manufactured products, we gain insights by taking those products into the clinics. This allows us to analyze not only the clinical data but also the translational data to better understand the role of manufacturing when the product is used in clinical settings. Our process development team is utilizing this knowledge to enhance the manufacturing process and further optimize the product beyond what we've achieved with the Alloy process. Currently, our focus, as Zach noted in his prepared statement, is on the 605 and 715 products. We anticipate reintroducing these products into the clinics sometime in 2024.

Operator, Operator

Our next question or comment comes from the line of Luca Issi from RBC Capital Management.

Luca Issi, Analyst

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 ORRs primary endpoint, while the randomized trial is smaller, but has PFS as primary endpoint, which will take a 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 early 2025?

Zachary Roberts, Executive Vice President of Research and Development

So what we've guided to is the 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.

Operator, Operator

Our next question or comment comes from the line of Asthika Goonewardene from Truist.

Asthika Goonewardene, Analyst

Just want to go back on the BCMA program quick. I just want to confirm that the manufacturing optimization of 605 is still ongoing? And then related to that, can you make the decision to choose which of these products you may want to actually take it to a pivotal study? We've seen some data with 715; we haven't seen a whole lot with 605. David and team, I just want to know, about how many patients' worth of data would you want to see with this now optimized 605 before you make that decision?

David Chang, President and CEO

So many layers of questions there. Let me first start with the 605. We have a very small number of patients, and as we've previously stated back in November of last year, we already started looking at the manufacturing process of 605. And now as Zach has said, we are also reviewing, since we're not moving forward with the 715 program into the pivotal for prioritization reasons, we have an opportunity to further review the manufacturing process of 715. So in a way, we are looking at the manufacturing process of both 715 and 605 concurrently to come up with what we believe is a more optimal manufacturing process. So the process optimization is exactly what we are talking about. And as I've said, we are probably looking 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 and stay tuned.

Operator, Operator

Our next question or comment comes from the line of Jack Allen from RW Baird.

Jack Allen, Analyst

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.

Eric Schmidt, Chief Financial Officer

Jack, it's Eric. Thanks for your question. Yes, we do intend to present updated datasets on both our CD19 programs, as well as our CD70 program in renal cell carcinoma. So 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 that we want you to have at the top of your list. And 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.

Operator, Operator

Our next question or comment comes from the line of Kalpit Patel from B. Riley Financials.

Kalpit Patel, Analyst

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 605 trial? Or is that still ongoing?

Zachary Roberts, Executive Vice President of Research and Development

Kalpit, we actually sat back at the showcase event in November, that we had paused enrollment in the 605 study as we work toward an improved manufacturing process for that construct. So that is correct. We are not currently enrolling in the 605 Phase I study.

Operator, Operator

Our next question or comment comes from the line of David Dai from SMBC.

David Dai, Analyst

I have a question about ALLO-316, specifically regarding the CAR T. Could you provide more details on the CD expression profile of the CD70-positive patients? What is the CD70 entity? Also, could you discuss the expression of some of these patients? Additionally, I have an important question about the T Cell profile and the depth of response.

David Chang, President and CEO

So David, this is Dave Chang. 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 highlighted approximately 15 patients that we have treated to date with ALLO-316 program. And what we have seen was, CD70 expression does make a big difference, and the responses that we have seen, and there were three out of nine patients who have achieved an objective tumor response. And all those cases occurred in the CD70 positive population. We are also looking at the level of CD70 expression to further optimize patient selection, but that is an ongoing process.

Operator, Operator

Our next question or comment comes from the line of Jason Gerberry from Bank of America.

Jason Gerberry, Analyst

I wanted to get your thoughts on the Galapagos point-of-care manufacturing model as a competitive approach, especially since a key aspect of the value proposition for 501A is the reduction in time to treatment. They claim a 7-day period, while there may be a 2 to 5 day wait for 501A after treatment decisions are made. Overall, I’m interested in your perspective on this competitive model. For my follow-up, regarding the BCMA update, with the likely shift to earlier lines with KarMMa-3 and its updates, it seems we are facing a higher bar and a changing landscape. As you consider long-term strategies for reentering the competitive field, do you see this as an elevated bar? I'm curious about how you perceive the evolution into earlier lines and its impact on your future development.

David Chang, President and CEO

All right. So two questions there. Let me take the Galapagos, as well as the point-of-care manufacturing. When I was at Kite, as we were looking at the future of cell therapy, I mean, certainly, the ease of autologous manufacturing, which there were many opportunities, could play a role. But when we sort of think about from the allogeneic angle, the benefit that allogeneic product provides is more than just to gain time. You're talking about patients not having to undergo leukapheresis, not having to be very carefully subjected to the manufacturing site availability and leukapheresis slot availability, and also manufactured product meeting the specification, which, as we have learned, as more and more autologous CAR T products are coming online, all these things play a role. And also, I think nowadays, everybody is aware, the lentiviral availability also plays a role in the manufacturing of CAR-T. In our case, manufacturing one lot allows treatment of many patients. So yes, it's great to see the progress being made in sort of different ways of manufacturing autologous CAR-T. But I think the allogeneic benefits still far outweigh what the autologous manufacturing can do, even with the point-of-care manufacturing. And the BCMA with earlier line, I'm going to answer that question as well. 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. And we believe that the profile that we have with 715, if we can even slightly improve the response rate beyond what we already have, and we already have the durability that's matching up with one of the proof of autologous CAR-T products. I think we will remain quite competitive in the BCMA space.

Operator, Operator

Our next question or comment comes from the line of Raju Prasad from William Blair.

Raju Prasad, Analyst

On the 316 program, you mentioned CD70 levels and the potential for going into liquid tumors. Just wondering if you could provide a little more color on that. I think there was a paper recently on kind of EGFR relapsed patients showing CD70 positive or CD70 as a marker. Just kind of curious of your thoughts on that as well and if that kind of crossed your play as far as potential indications to look at?

Zachary Roberts, Executive Vice President of Research and Development

Thanks Raju, for the question. So CD70, we think, is a great target for a number of reasons, including its wide distribution on a number of different malignancies. So 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. And of course, we saw that same report that you did and are looking into that carefully. On the heme malignancy side, obviously, T-cell malignancies, lymphomas and leukemias are well described as having high expression of CD70. That's also found on myeloid malignancies like AML and also in diffuse large B-cell lymphoma, a substantial fraction of those patients express CD70. So 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 into additional avenues.

Operator, Operator

Our next question or comment comes from the line of Tony Butler from E.F. Hutton Group.

Charles Butler, Analyst

Sorry about the confusion. This is about CD70. I want to know what you can share with us about the current status of the assay development, whether it's internal validation or getting validation from CLIA, the potential timing of when you hope to deploy this for patient selection, and whether the next CD70 program update will include the possible number of patients who have been prospectively selected for the expression.

David Chang, President and CEO

Yes. So this is Dave Chang. Let me just answer the question about the status of the diagnostic assay. We have developed and validated a diagnostic assay to be used in the renal cell cancer patients. In fact, the assay has already been deployed to select the patients in the 316 study. So as is the case with any kind of in vitro diagnostic assay that's being used for patients in different indications, additional validation has to be done, and all that work is ongoing. As I said, as Zach has said, the CD70 program, we have many different opportunities and it remains as one of the most exciting programs that we're dealing with right now.

Operator, Operator

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.

David Chang, President and CEO

Thank you again for joining the call today. We can tell from all of this call, we are most enthused ever about the opportunity before us. We are excited about the role we are planning 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.

Operator, Operator

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