Q4 2022 Allogene Therapeutics Inc Earnings Call

Speaker 1: The conference will begin shortly.

Speaker 2: To raise and lower your hand during Q&A, you can dial star 1 1.

Speaker 3: Good day, ladies and gentlemen, and thank you for standing by. Welcome to Allergen 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 1-1 on your telephone keypad.

Speaker 3: 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.

Speaker 4: Thank you, operator, and welcome to our call. Today after market closed, Allergan issued a press release that provides a business update and financial results for the fourth quarter in 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.

Speaker 4: 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.

Speaker 4: 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.

Speaker 4: 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 FCC disclosure documents. You are cautioned not to place undue reliance on these forward-looking statements, and Allergan disclaims any obligation to update these statements. I'll now turn the call over to David.

Speaker 5: Thank you, Christine, and thank you to all who have joined our call. The new virus in 2023 will mark the fifth year since Alagen's infection.

Speaker 5: Each year, as our organization has matured, our work takes on a greater and greater importance for the patients we aim to serve. Algin was conceived shortly after the first photologous carpe therapies were approved by the FDA. For many, many years, Algin has been working with dude- milking individuals with Nin zombie Win needs, family members and patients.

Speaker 5: 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.

Speaker 5: but the clinical success achieved by the orthologous cell therapies has also heightened its demand as well as its inherent limitations.

Speaker 5: As an individualized therapy, the technology is limited by a lack of scalability and timely delivery.

Speaker 5: Today, it is estimated that one out of ten patients in the US 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 a talent therapist to meet the growing need. We are now facing a crisis as patient demand far outweighs the ability for a talent therapist to meet the growing need.

Speaker 5: thereby constraining the growth of this modality and limiting access for patients. Unfortunately for patients, time is not a luxury that can afford.

Speaker 5: Yet we continue to hear from physicians that the complexities and delays in manufacturing are limiting which patients can access CAR key therapy. And allergen, we have always envisioned a different future for CAR key, one in which self-product.

Speaker 5: 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 RP showcase late last year demonstrates it is no longer a question of if, but when this vision will become a reality.

Speaker 5: And as we begin our fifth year, I believe the timeliness of when we will be able to execute on this vision are becoming increasingly clear as evidenced by our ongoing and potentially cover of phase two study in large, these dull and former.

Speaker 5: For those of us immersing 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,

Speaker 5: 92% of all enrolled patients receive products with 100% of infused products manufactured and released for product specification.

Speaker 5: In contrast to a phyllo cell therapy, patients were able to start treatment within two days of enrollment with no breaching treatment. And unlike by specifics, treatment consists of one-time dose, three of the hassle, inconvenience, and cumulative toxicity of chronic treatment that can continue for months on end.

Speaker 5: Allocart is unique in its ability to provide an off-the-shelf product with one-time administration.

Speaker 5: True innovation is often met with initial skepticism. Those of us involved in the initial development of Ocalus Charterto's member, the Naysayers, who said it could not be done. But today, despite its inherent limitations, the therapy some of us played a role in developing at Kaiparma.

Speaker 5: is considered a glass breaking therapy for non-absentive lymphoma and has achieved blockbuster status.

Speaker 5: The skepticism toward allogeneic RT is no different today than what we face 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-hospital lymphoma.

Speaker 5: We also have data that shows an allogeneic CAR-T is on the path of competing favorably in multiple myeloma and early but exciting crucial concept data in bile of tumor. Now we are fortunate to be leaders in this innovative field.

Speaker 5: we know the only thing that will quiet the skeptics is execution, execution on clinical development, execution on manufacturing, execution for its PLA filing, and commercialization.

Speaker 5: Fortunately, we had outstanding talent and other resources to execute on the industry's first phase two potential pivotal trial.

Speaker 5: And it is for that reason, especially excited to have next to me, Dr. Zachary Roberts.

Speaker 5: 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. And some of the first heads understand that the urgency and challenge we often embrace is to give back to patients and their loved ones.

Speaker 5: something they so desperately desire, time.

Speaker 5: I will not let you invite the active providers perspective on our arcoid 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 Alligene. I think that when you join an organization, it's an opportunity to bring a fresh perspective and regain sight of forests through the trees.

Speaker 6: So despite knowing many of my new allergy colleagues for quite some time and having followed the company since inception, I initially carried an outsider's perspective.

Speaker 6: And when I had the opportunity to join the R&D showcase last November , I was freshly exposed to everything about Allergane. The professionalism of the leadership team, the engagement of its stakeholders, the passion of its investigators.

Speaker 6: 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.

Speaker 6: and all of this with an Allergen AXL therapy product. For Allergen 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.

Speaker 6: And I'm colleges who used to care for these patients and someone who has been working every single day in self 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 Alligene 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 in Alligene for about two months and as David has rightly noted, the vaulted.

Speaker 6: 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 1 data, our ongoing Phase 2 study, and what the availability of allo-CART-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

Speaker 6: a league of our own and we welcome the responsibility that comes with it.

Speaker 6: 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.

Speaker 6: of patients 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.

Speaker 6: With four patients still awaiting six months follow-up time at the data cut, the lowest possible durable CR8 is 33%. That would remain solidly in the range established by the approved autologous CAR T cells for non-Hodgkin's lymphoma. What is a standout among our data is that all of the patients treated in our trials received an InSpec product. 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 1 trials, we demonstrated a manageable safety profile with no observed dose limiting toxicities.

Speaker 6: the contribution of ALOS 647 to the Lympho Depletion Regiment, which will be open to enrollment early in the second quarter.

Speaker 6: We are preparing for a phase three study in earlier line, large B.Cell and POMA targeting trial initiation in the first half of 2024. We are preparing for a phase four study in early line, large B.Cell and POMA.

Speaker 6: Now, moving to BCMA. Just last month, data from the Phase 1 universal trial of HALL-0715 in relapsed refractory multiple myeloma was published in Nature Medicine. The corresponding editorial by renowned NCI researchers, Drs. Jennifer Brunnow and Jim Kochenderfer reinforced what we've known to be true. The universal study has demonstrated that an off...

Speaker 6: anti-VCMA CART-T to demonstrate proof of concept in multiple myeloma with response rates that are similar to an approved autologous CART therapy. The most recent data we presented on AL-715 at Ash in December demonstrated substantial and durable responses.

Speaker 6: 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 SVA 60 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 over his entire senior year, while music with 2ths and study Tennessee is

Speaker 6: today in no GVHD.

Speaker 6: Eight patients, or 29%, experience grade 3 or higher infections, and eight patients experience prolonged grade 3 or higher cytopenias. While we remain very excited about what ALICE-M15 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 will be able to see the results

Speaker 6: We are evaluating manufacturing process improvements across our BCMA candidates, ALOS 715 and ALOS 605, to achieve optimal performance. Through our work in hematologic malignancies, we have established proof of concept for our platforms, including a proprietary approach to lymphoid depletion using ALOS 647 to create a window for cell expansion and persistence.

Speaker 6: evaluating manufacturing process improvements across our BCMA candidates, ALO715 and ALO605 to achieve optimal performance. Through our work in hematologic malignancies, we've established proof of concept for our platform, including a proprietary approach to lympho-depletion using ALO647 to create a window for cell expansion and persistence. But this is just the beginning.

Speaker 6: 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. ALO-316 is being evaluated in TRAVERSE, a Phase 1 study of patients with relapsed refractory renal cell carcinoma. In RCC, standard of care includes two main classes of therapies, TKIs, or tyrosine tiniase 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 TIVAZINAB 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.

Speaker 6: These data highlight the profound unmet medical need in advanced stage renal cell cancer. Initial data from our traverse study demonstrated promising anti-cancer activity in the subset of nine patients with confirmed CDC 70 positive RCC. As of the data extract date, the disease control rate was 100 percent 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.

Speaker 6: low grade, reversible, and seen in only three patients.

Speaker 6: The data that we've shared suggests that patients who have measurable CD-70 expression tend to do better in terms of response than those who have absent or unknown levels of CD-70.

Speaker 6: So we are now deploying a new investigational in vitro companion diagnostic assay designed to prospectively assess CD70 expression levels to enhance patient selection.

Speaker 6: In the diverse trial, we plan to complete dose exploration and initiate expansion co-vor enrollment in 2023.

Speaker 6: We may also investigate allo-316 for other CDX70 expressing solid tumors and hematologic indications.

Speaker 6: or in combination with other anti-cancer therapies, such as immune checkpoint inhibitors.

Speaker 6: Our CD70 Phase 1 dataset was also notable for the high levels of CAR T cell expansion and persistence that were observed in the study.

Speaker 6: We believe that this may relate to the use of a novel anti-rejection technology that we call DAGR. This technology is designed to enable alocarti cells to resist rejection by the host immune cells, enabling a prolonged window of persistence.

Speaker 6: during which alocar T cells can expand and actively target and destroy cancer cells. The DAGR platform arms alocar T cells with a CD70 targeting receptor designed to recognize and deplete aloreactive CD70 positive host T cells, while also masking the CD70 molecule expressed on the alocar T cells themselves, thus preventing the alocar T cells from killing one another in a phenomenon known

Speaker 6: 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.

Speaker 6: 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 it's 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 advances in the environment.

Speaker 6: 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.

Speaker 6: 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 number one, executing on our phase two CD19 pivotal trials, number two, evaluating the best path fast-forward for multiple myeloma, and number three, continuing to progress our ALO-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 expectation, the company expects the cash runway to be $2.5 million.

will be sufficient to fund operations into 2025. We expect our full year 2023 gap 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.

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 cents per share, including non-cash stock-based compensation expense of $83.6 million. With that, we will now open the call for your questions. Thank you.

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 you 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. Stand by. Mr. Yee, your line is open.

Hi, good afternoon. This is Jenna. For Mike. Thanks for taking your question. We wanted to catch up on city 19. What are you seeing in terms of the enrollment for the paper? 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.

Thanks, David. So the enrollment in the Alpha 2 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 the 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 and general and for a moment. Thank you. Our next question to comment comes from the line of Tyler Van Buren from Goldman Sachs. Mr. Van Buren, I mean from Cowlin, Mr. Van Buren, your line is open. Thank you very much for taking the question. Given the prioritization of the earlier line, large B cell lymphoma trial for all of 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 S-card second mine, Sumis 7 trial, or if there might be some differences. Hi Tyler. I thought a second, but then you hadn't 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. You know, we have a very compelling data in 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 Anomita on for Selvene. On the potentially pivotal trial in multiple bioloma, 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 cells 4-1? Thank you for taking our question. All right, let me take that question and I'm just going to...

the compelling data we have, and also the study that we are conducting is potentially a pivotal study. So for all the obvious reasons, our priority is alpha-2 study. And along with that, as we have just talked about, moving the program to the earlier lines, that becomes an important option in a day we want to exercise as early as possible.

We are thinking that the pivotal study for the multiple myeloma will not be 2023. It will be pushed out to more likely 2024, during which time 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 we can optimize the process as best we can across different aspects that we have, whether it's 715 or L605.

Thank you. Our next question or comment comes from the line of Brian Chang from JP Morgan. Mr. Chang, 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 Alpha 2 in the first half of 2024.

Do you need some patience to be those of the allied process manufacturing process before filing for approval and any updates on getting the allied process in?

Hi, Brian . I'm going to ask Zach to respond to your question. Hey, Brian . So the alloy X process is currently – I think his question was alloy process. Sorry.

Yeah, the alloy process. Sorry about that, I got confused. So yes, the alloy process is the process that we're taking forward in both of the PIVITL trials for ALLO 501A. This is the manufacturing process that we discussed at length at the RDS and the one that we believe is the most appropriate to take forward into the PIVITL study. So, thank you.

All of the patients dosed in both Xpand and Alpha-2 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 going to be mostly reserved for solid-tumor programs or if this could be eventually deployed across...

you know, 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 lympho depletion 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. I think it really defines how we're thinking about DAGR. So as you rightly point out, the expansion data that we saw in the early data from the traverse study do support that they're...

So 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 pre-clinically to try to...

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 and then what do you need to see to opt into the ex-U.S. rights for 501A? Thank you. Yeah, I'll take that. This is Eric. Thanks for the question. As you know,

the ex-US 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 in whether we exercise the option or not will obviously be based on a number of factors, some financial, some developmental, so stay tuned we hope to provide you 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. So, just had a question about the patient enrollment for the pivotal studies for 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 2 treatment. I think there's some concern, not a whole lot of that.

Some physicians may sort of, whatever even not want to put patients that they would normally put on a total dystopia on your treatment. Also, I noticed in the press release, patients may receive treatment in the outpatient setting at the investigator's discretion. Here's what you can talk about exactly how that's going to be different. It's going to be sort of full outpatient or sort of a combination between what we think of as outpatient and invitation. Thanks.

One of the things that we 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 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, what is the best way to do this?

patients appropriately. Thank you. Our next question or comment comes from the line of Renee 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 that are taking place, you know, especially for like 605 and 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? And when do you think, you know, you might actually start resuming enrollment with the new

do have benefits of having taken those products into the clinics. And this is really the opportunity to interrogate not just the clinical data, but the translational data to really understand how the manufacturing plays out when the product goes into the clinics. So that is sort of fund of the knowledge that we have.

as Zach had mentioned in his prepared statement, on the 6.5 and 7.15. And for the timeline of reintroducing those products back into the clinics, we are probably looking at some time in 2024. Thank you.

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

Oh, great. Thanks so much for taking the question. Congrats on the progress. Just a quick one. If you're 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 ROR as primary endpoint, while the randomized trial is smaller but has PFS as primary endpoint, which will take longer time to readout. Cool. Now there's one thing I can really appreciate and really enjoy about the headline of this comment.sel

How will these factors offset each other? Would it be fair for us to assume that both trials were read out in early 2025? Thanks so much. So, what we've got to do 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 Alpha 2 and expand at roughly the same time.

Thank you. Our next question or comment comes from the line of Asfika Guduwadini from Truist. Mr. Guduwadini, your line is open. Hi, guys. Asfika Guduwadini from Truist here. Thanks for taking my question. Just want to go back on the BCMA program quick. I just want to confirm that the main patching optimization of...

or five is still ongoing. And then related to that, to make the decision to choose which of these products you may want to actually take into a pivotal study, we've seen some data with them on five. I haven't seen a whole lot with six or five. David and Tim, just one note, but how many patients worth of data would you want to see with this now optimized six or five before you make that decision? Thank you. So, you know, many later questions there.

prioritization reasons, we have an opportunity to sort of 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 more of an optimal manufacturing process.

So, you know, the process optimization is exactly what we are talking about, and 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 and stay tuned. Because almost the swamp is

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 allergy, but I was hoping you could dive a little bit more into what we should expect throughout the course of 2023.

Do you think we 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 in one we choose. But those are the two milestones that 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. Thank you. Our next question of comment comes from a line of CalPIT Patel from B. Rally 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 605 trial, or is that still ongoing?

We actually said back at the showcase event in November that we had paused enrollment in the 605 study as we worked toward an approved manufacturing process for that construct. So that is correct. We are not currently enrolling in the 605 phase 1 study. Thank you. Our next question or comment comes from the line of David Dye from SMB.

He's a bossy family patient and we're just in question. He's profiled with a depth of response.

So, David, this is Dave Chang. You're breaking up a little bit, but I think the question was centered around CD7D expression in the ALO316 program. In the R&D showcase, we highlighted approximately 15 patients that we have treated to date with the ALO316 program.

And what we have seen was CD7D expression does make a big difference. And the responses that we have seen, and there were three out of nine patients who have achieved a objective tumor response, and all those cases occurred in the CD7D positive population. And we are also looking at the level of CD7D expression to further optimize the patient selection, but that is an ongoing process.

given your key to the value proposition for 501A is the shortening of the vein at any time. They claim to kind of have a seven day period. Ultimately, there's like two to five days that may transpire between getting 501A ultimately from time of treatment decision. So

Overall, just maybe less curious to get your perspective on that as a competitive approach. And then for my follow-up, just on the BCMA update, just given the likely shift to earlier alliance here with the Karma 3 and Carta 2.4 updates, that's going to make for just an elevated bar and changing landscape. So as you guys think about longer-term reentering the competitive mix, 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 will play into your future development. All right. So, you know, 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, you know, when we sort of think about from the allogeneic angle, the benefit that allogeneic product provides is more than just paying-to-beighing time.

You're talking about patients not having to undergo leukopheresis, not having to be very carefully subjected to the manufacturing slot availability and leukopheresis slot availability, and also manufactured product and meeting the specification, which as we have learned as more and more power product products are coming online, all these things does play a role. And also, I think nowadays everybody is aware that…

manufacturing. And you know the BCMA with the earlier lines, I'm going to ask that question as well. You know right now I think the BCMA or College Card Key, 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 improved response rate beyond what we already had. We already had the durability that's matching up with one of the proof of POSC active products. I think we will remain quite competitive in the BCNA space. Thank you.

Our next question or comment comes from a line of Raju Prasad from William Blair. Mr. Prasad, your line is now open. Thanks for taking the question. On the 316 program, you mentioned CD70 level and the potential for going into liquid tumors. One of you probably a little more color on that. I think there was a paper recently on kind of EDFR relaxation showing CD70 positive. Um.

CD70 as a marker. Just kind of curious your thoughts on that as well and if that kind of crossed your play as far as potential indications to look at. Thanks. Thanks, Raju, for the question. So the 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. It's not just a

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, you know, of course we saw that same report that you did and are looking into that carefully. On the hemolygacy side, you know, 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, substantial fraction of those patients expressed 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 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. Please go ahead, Mr. Butler. Thank you. Sorry about the confusion. This is about 3,070.

I want to, you know, what you can share with us about the current status of the AFAP development, you know, whether it's, you know, the internal validation versus getting validation from clear, 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 in prospecting this lecture for the expression. Yeah, so this is the change. Let me just answer the question about the status of the...

many different opportunities and it remains as one of the most exciting programs that we're dealing with right now.

Thank you. I'm sure no additional questions indicate 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 from all of this call, we are most induced ever 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 not disconnect. Thank you. Ladies and gentlemen, thank you for your participation in today's conference. This does conclude the program, and you may now log off and disconnect.

Again shortly. To raise and lower your hand during Q&A you can dial star 1-1.

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