Allogene Therapeutics, Inc.

Hello, thank you for standing by and welcome to Allogene Therapeutics fourth quarter and full year 2024 conference call. After the speaker's presentation, there will be a question and answer session. To ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. Please be aware that today's conference call is being recorded. I would like to turn the call over to Christine Cassiano, Chief Corporate Affairs and Brand Strategy Officer. Ms. Cassiano, please go ahead.

Thank you, operator, and thanks to all of you for joining this call. After the market closed, Allogene issued a press release that provided a business update and financial results for the fourth quarter and full year of 2024. This press release and today's webcast are available on our website. Following our prepared remarks, we will host a Q&A session. We recognize that historically questions have been multifaceted, but note that we will endeavor to keep this call to under an hour. I'm joined today by Dr. David Chang, President and Chief Executive Officer, Dr. Zachary Roberts, Executive Vice President of Research and Development and Chief Medical Officer, and Jeff Parker, 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, the safety and efficacy of our product candidates, commercial market forecasts, and 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 press release and latest SEC disclosure documents. Your caution not to place undue reliance on these forward-looking statements, and Allogene explains any obligation to update these statements. I'll now turn the call over to David.

Thank you and welcome, everyone. It's a pleasure to be speaking with you today. At the start of 2024, we set forth a bold strategy that some viewed as merely words on PowerPoint with a distant horizon. A year later, we stand on the brink of a transformative year at Allogene. Pioneering Allogene-Carty therapy was never expected to be easy. It demands vision, rigorous science, relentless persistence, and operational excellence. Today, all three of our key programs are approaching critical milestones, marking the tangible progress of our dedication. We enter 2025 stronger than ever with a differentiated pipeline and a clear path to shaping the future of Allogene-Carty. Our programs in large B-cell lymphoma, autoimmune disease, and renal cell carcinoma are breaking new ground, reinforcing our commitment to making -the-shelf cell therapy a new standard pair. Our pivotal Phase II Alpha-3 trial for semicell in first-line consolidation large B-cell lymphoma is widely considered to be groundbreaking. We are immensely proud of the innovation behind this trial. The enthusiasm from both community cancer centers and leading academic institutions has been truly energizing, and momentum continues to build with 40 sites now activated. We anticipate reaching a critical milestone with the lympho-depletion selection and fertility analysis around mid-2025. This interim analysis will provide essential insight into whether our approach is on track to meet its objectives, providing a clear signal of progress when we select our lympho-depletion regimen. Beyond oncology, 2024 also marks our official expansion into autoimmune disease with Allogene-329, the first of its kind CD19-CD70 dual-targeting Allogene-Carty product candidate powered by our proprietary Dagger technology. Earlier this year, we secured FDA clearance for our Phase I resolution basket trial in rheumatology. An important step towards delivering a scalable -the-shelf CAR-T options to the best number of patients who stand to benefit. The IND clearance for Allogene-329 cements Allogene as a true innovator in the autoimmune disease space. We did not follow the crowd. We deliberately took the time to ensure our approach was differentiated, developing both an investigational product and trial specifically to address the unique challenges of autoimmune disease. Allogene-329 is designed to induce lasting remission by targeting both T cells and activated T cells. An equally important design feature is incorporation of our Dagger technology, which has the potential to reduce or even eliminate the need for lympho-depletion. If successful, this breakthrough could fundamentally change how CAR-T therapy is deployed in autoimmune diseases. With the resolution trial slated to launch in mid-2025 and proof of concept data expected by year-end, we believe Allogene-329 represents a new frontier in allogeneic cell therapy that will showcase the power of our platform to redefine treatment paradigms beyond oncology. In cell tumors, Allogene-316 is emerging as a promising and potentially groundbreaking asset in renal cell carcinoma. The phase one data we presented last year underscores the potential of Allogeneic CAR-T therapy to drive meaningful responses in cell tumors. An area where cell therapies have historically faced immense challenges. With our regenerative medicine advanced therapy designation, Allogene-316 has the potential to redefine treatment for advanced renal cell carcinoma, bringing a much needed innovation to patients with limited options. In mid-2025, we plan to share an update from our phase 1B cohort focusing on durability, a key factor in improving long-term patient outcomes. From a broader perspective, the momentum across our program highlights the potential of Allogeneic CAR-T therapy to disrupt multiple disease areas. We aim to not just compete with autologous therapies. We are demonstrating that Allogeneic approaches can surpass them in accessibility and scalability. Our bold pivot in 2024, coupled with our relentless execution, affirms that we have the right team, science, and strategy to make 2025 a breakthrough year for Allogene, one that defines the future of Allogeneic CAR-T therapy. I would like to now hand the call over to Zach to provide further details on our clinical programs.

Thank you, David. We take great pride in our clinical progress across our R&D organization and the company as a whole. All three of our cutting-edge programs demonstrate significant promise, reinforcing the strength of our science and execution. We are energized by the momentum in our pivotal semicell trial in first-line consolidation LBCL, the upcoming launch of the resolution basket trial with Allo329 in rheumatology, and the compelling data emerging from Allo316 in advanced renal cell carcinoma. Let's start with the foundation of our programs. The field has questioned for years whether an Allogeneic CAR-T could deliver durable responses. With multiple patients with relapse for fractory LBCL and ongoing complete remissions beyond four years, we now have proof that our products can achieve that. The Journal of Clinical Oncology's recent publication of our Phase I Alpha Alpha-2 trial results in relapse for fractory large B-cell lymphoma marks a defining moment for the field. These findings represent the most comprehensive Allogeneic CAR-T dataset to date. The study showed efficacy comparable to approved autologous CAR-Ts with an overall response rate of 58% and a complete response rate of 42% across the study, increasing to 67% and 58%, respectively, with the pivotal study regimen. Importantly, treatment delivered exceptional durability with a median duration of response of 23.1 months and median overall survival not reached in patients who attained CR. We also observed a potentially -in-class safety profile with no cases of -versus-host disease, immune effector cell-associated neurotoxicity syndrome, or high-grade cytokine release syndrome. The median time to treatment was just two days, significantly shorter than the week's long wait times acquired for autologous CAR-T. Moreover, these results provide compelling evidence supporting the use of CAR-T therapy in patients with low disease burden. A growing body of research indicates that earlier intervention with CAR-T, when the disease burden is minimal, can lead to improved safety and efficacy outcomes, and this study reinforces that premise. Among patients with baseline tumor burden of less than 1,000 mm2 or normal LDH levels, a key biomarker of low disease activity, the complete response rates were 100% and 82%, respectively. These findings strongly support semicell as a breakthrough therapeutic option for patients with minimal residual disease, which is the population studied in Alpha 3, the first randomized trial evaluating CAR-T as first-line consolidation therapy for MRD-positive patients. With semicells 100% CR rate in patients with low but still radiographically evident disease burden in these earlier trials, Alpha 3 presents an unprecedented opportunity to both predict relapse and intervene before it occurs. If successful, Alpha 3 stands to upend the standard of care in first-line LBCL, potentially marking the first significant advance to the treatment paradigm in the last 25 years. Since the trial's launch in June, we have made steady progress. Today, we have successfully activated 40 of the planned approximately 50 sites with roughly a 50-50 split between community cancer centers and academia, and we are progressing towards the first key milestone in Alpha 3 trial, the lympho depletion regimen selection anticipated around mid-2025. Beyond signaling progress and accrual, the lympho depletion selection step is paired with a futility analysis, and thus our decision to proceed will be a critical indicator that the trial is on track to meet its objectives based on early data. Moreover, this milestone will help map the registrational path forward, further solidifying our confidence in semicells' potential to redefine the standard of care. Due to the seamless pivotal design, these early patients' results count towards the pivotal analysis, and therefore we will not be releasing detailed efficacy or safety outcomes to protect trial integrity. Beyond LD selection, we plan to conduct an interim EFS analysis, which will be overseen by the Independent Data Safety Monitoring Board in the first half of 2026. The primary EFS analysis data readout is expected around year-end 2026, with a potential BLA submission in 2027. None of this would be possible without the great partnership of Forsyte Diagnostics and their ultra-sensitive CTDNI-based Clarity assay powered by PhaseSeq. For this reason, we expanded our strategic collaboration with Forsyte to support the EFS-Diagnostics and CTDNI assay as a companion diagnostic in the EU, UK, Canada, and Australia to support allergen's clinical development of semicell. Shifting gears to autoimmune diseases, in January 2025, the FDA cleared the IND for the Phase I Resolution Basket Trial, a -its-kind study evaluating Allo-329 and systemic lupus erythematosus, lupus nephritis, idiopathic inflammatory myopathies, and systemic sclerosis. This true basket design brings significant operational efficiencies, allowing enrollment access to a broad patient pool with a single IRB approval. This is one of several differentiating factors that may prove advantageous in this competitive space. The strategy behind Allo-329 stems from two key observations. First, autologous CAR-T data suggests that short-term CAR-T persistence is sufficient to reset the immune system in autoimmune diseases, contrasting with the months to even years-long L-Persistence needed in oncology. Since B-cell depletion lasts around 100 days in autologous studies, allogeneic CAR-T's natural 2- to 4-month persistence makes it uniquely suited for autoimmune therapy. Second, data from our Phase I Allo-316 program in kidney cancer demonstrated that our Dagger technology intrinsically enhances cell expansion and persistence, allowing us to significantly reduce the intensity of lympho depletion without sacrificing efficacy. These insights shaped Allo-329, which includes the Dagger technology and is intended to enable reduction or even elimination of lympho depletion, a major differentiator in autoimmune treatment. The resolution trial will immediately test the requirement for lympho depletion in parallel cell dose escalation pathways. In one, we will use a single infusion of cyclophosphamide at a dose used in rheumatology, and in the other, a CAR-T only arm with no lympho depletion relying entirely on the Dagger effect. The trial is set to launch mid-year with proof of concept data expected around year end. With extensive preclinical validation, published data, and an optimized design, Allo-329 is positioned to be the most rigorously designed allogeneic CAR-T program for autoimmune disease to date. Beyond rheumatology, its potential extends to nephrology, neurology, hematology, and bowel disease, paving the way for a new era of CAR-T therapy in immune-driven conditions. Last quarter, I highlighted Allo-316 and its remarkable potential following data that showcased encouraging responses from a single infusion with an impressive 50% best overall response rate and a 33% confirmed response rate in heavily pretreated metastatic kidney cancer patients whose tumors expressed high levels of CD70. Given that update, I'll keep it brief today with just a reminder of the next steps for this promising program. We have completed enrollment in the Phase 1B Expansion cohort, which is assessing safety, efficacy, and durability of Allo-316, at dose level 2, or 80 million CAR-T cells, following standard lympho depletion with fludarabine and cyclophosphamide. As we continue to evaluate outcomes, we will determine the best path forward, including the potential to pursue a strategic partnership. We expect to share data from this cohort in mid-2025. I'll now turn the call over to Jeff.

Thank you, Zach. I'll focus my remarks on our financials. Our financial position is strong and we continue to operate with capital discipline, ensuring we are well positioned to advance our pipeline and pursue our strategic objectives. As of December 31, 2024, we had $373.1 million in cash, cash equivalents, and investments, with our cash runway extending into the second half of 2026. Research and development expenses for Q4 2024 were $45 million, including $5.6 million in non-cash, stock-based compensation expense. For the full year of 2024, R&D expenses totaled $192.3 million, including $20.4 million in non-cash, stock-based compensation. General and administrative expenses for Q4 2024 were $15.5 million, including $7.3 million in non-cash, stock-based compensation. For the full year, G&A expenses were $65.2 million, including $31.3 million in non-cash, stock-based compensation. Net loss for Q4 2024 was $59.9 million, or $0.28 per share, including $12.9 million in non-cash, stock-based compensation. For the full year, net loss was $257.6 million, or $1.32 per share, including $51.7 million in non-cash, stock-based compensation, and $15.7 million in non-cash, impairment of long-lived asset expense. Turning to guidance for 2025, we expect a cash burn of approximately $170 million. We expect full year 2025 GAAP operating expenses to be approximately $250 million, which includes an estimated non-cash, stock-based compensation expense of approximately $50 million. This guidance excludes any impact from potential business development activities. We'll now open the call for questions.

Thank you. As a reminder, to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. One moment for questions. Our first question comes from Tyler Van Buren with TD Cowan. You may proceed.

Hey, guys. Thanks very much, and congratulations on all the progress. My question was just following up on the recent JCO publication that you highlighted and thinking about the read-through as to the ongoing Alpha-3 trial. How do patients with low disease burden in the publication compare to those being enrolled in Alpha-3 as we think about the high complete response rate holding up in Alpha-3?

Hi, Tyler. Excellent question. I think one thing that we highlighted in our JCO paper, and this is in fact something that we have been saying for some time based on what has been seen in otolus car T therapies. When you look across patients who have been treated with CAR T, I think this extends not just CD-19 but with other PCMA or other antigen-targeted CAR T and T malignancies. There is a very strong correlation of likelihood of response as well as likelihood of experiencing adverse events, serious adverse events. Actually, it's an inverse relationship in the latter case. When the disease volume goes down, the likelihood of response is much higher. At the same time, the probability of having a serious adverse event goes down. That has been seen numerous times, and there are many publications on that. Essentially, in the JCO paper, we were showing that essentially the same all is true for the alginate CAR T. They're probably not that surprising. I think this really bodes well for what we're doing, not only in the Alpha 3 study but also as we think forward into the autoimmune program with ALO 3-9. Specifically about your question, in terms of estimating the disease volume of MRD compared to patients who are studying the second-line study, there is some information that we have done together with full-size diagnostics. MRD positivity is about two hundredth less disease volume than patients who are presenting with disease for the start of the second-line treatment. Your particular question about how that compares with the low volume, the two categories of low disease volume that we have published in JCO, LVH or the tumor measurement. I would more or less extrapolate to about the same degree of lower disease volume as we have previously reported together with full-size in the second-line setting versus MRD positive.

Thank you. Our next question comes from Michael Yee with Jeffreys. He may proceed.

Hey, good afternoon. Congrats on all the progress. As we are thinking about the mid-25 futility and lympho depletion decision, I wanted to get your affirmation that you believe that 647 is extremely likely to not be needed and that should be the general Wall Street expectation. I believe that would be a positive for a number of reasons. And then as we get to the first half of 26, which would be around the corner, it does an interim DSMB efficacy analysis. What is the criteria number of events or is there a very high p-value bar on that? What do you expect? What should we expect at that interim? Thank you.

Hi, Mike. I'm going to defer your questions to Zach. Zach, can you take those two questions?

Of course. Thanks, Mike, for the great question. And so our opinion on the lympho depletion selection is sort of agnostic. I think you raise a fair point that not needing 647 brings some attractive attributes. Like it would be simpler for us for registering one entity instead of two. It certainly would be cheaper for us to do it that way. However, we see requiring 647 is actually potentially beneficial as well because that's part of our proprietary regimen. So it would help kind of protect our status here as the only therapy that is optional in this particular clinical setting. So we have designed this clinical trial to give us a solid answer to that question. Is 647 needed in this unique clinical trial or is it not? I think we can work with either independently. Both have upside for us. Sorry, Mike, will you repeat the second question? I've forgotten that one.

Yeah, yeah, yeah. Right around the corner, and this is in 12 months or so, is the interim by DSMB. Well, what is the criteria? Is it a high bar because you don't want to spend alpha there? But obviously, investors have had great discussions with you about how the drug is clearly going to be working here. You could definitely have a chance of hitting there. Thank you. Yeah,

so we haven't disclosed a lot of the specifics around the nature of that analysis, such as some of the specifics that you're requesting, except to say that it is a formal efficacy test where we will be testing the hypothesis with the primary endpoint of event pre-survival. There will be some minimal alpha spent. So it is quite possible, just given the way this study is designed, that we could end up with a statistically significant finding there, which would, of course, allow us to initiate conversations with the FDA, begin to kind of move more briskly across the other elements that need to fall into place to launch the program in the coming months after that. So we are looking forward to that analysis. And in either case, whether it meets statistical significance or it doesn't, we look towards that as a very significant sort of milestone in the delivery of this program.

Thank

you. Thank you. Our next question comes from Salvin Richter with Goldman Sachs. He may proceed.

Hey, this is Mark on for Salvin. Thanks for taking our question. For ALS329 and the trial starting soon in autoimmune disease, what data are you looking to show by year end to demonstrate proof of concept? And maybe more importantly, since there are many CD19 players and also allogeneic players showing data this year, how do you think your approach is differentiated and could your year end data support said differentiation? Thanks.

Hi, Mark. This is Dave Chang. Let me take on that question. So 3 to 9, we have cleared the IND and we expect to initiate the clinical study mid-2025. And we have been guiding towards the proof of concept data towards the year end. The number of patients that we expect to treat in 2025, because this is dose escalation phase one study, will be somewhat limited, but it will be handful. And what we are looking for is biomarker-based proof of concept. One, do allogeneic ALS329, do they expand well? I think those are very important information. And second, do we achieve the B-cell depletion while also allowing some of the B-cell recovery to occur? These are some of the important information that will lead to the proof of concept. And also, in some of the patients that we treat, we expect them to have autoantibodies and the measurement of autoantibodies before and after the treatment. That could also give a lot of insight into what the program is doing. In terms of differentiation of ALS329 to many other programs that are currently in the autoimmune space, I think the key is that one, this is an allogeneic program. And two, this has ability to not only deplete the B-cells, but also activate the T-cells, which contributes to the overall pathogenesis of autoimmune disorders. How the latter would translate, I think we will have to see the clinical data. But possibilities of being able to address the T-cells can allow us to go to indications that CD19 B-cell targeting therapies may not necessarily be sufficient. And another potential benefit of targeting T-cells is that the remission could be much longer because you are eliminating not just B-cells, but also T-cells. Awesome. Thank you.

Thank you. Our next question goes from Brian Chang with JP Morgan. You may proceed.

Hey, guys. Thanks for picking up questions this afternoon. David, I'm just curious if you can provide a little bit more comments around your latest thinking around incorporating potentially other milder lympho-depleting agents or even completely removing the standard SIFLU that you're using, any color and timeline, and what is really the fastest and the best way to sort that out? Thank you.

Yeah. I mean, Brian, excellent question. These are the things that we hope to address in the Phase I study. In the plan study, first of all, the lympho-depletion that we will be deploying is a milder lympho-depletion. We have taken out flu-darbin. So one cohort will be treated with a cyclophosphamide alone as a lympho-depletion. In a second one, we have also clarified when we announced the clearance of IND is that in parallel, there will be a second cohort where we will be testing without any lympho-depletion. So a little bit to your question as well to the previous question from Mark is really the Phase I study already is built in to address the key questions about 329, whether it can achieve the objective with milder, which will be fantastic news, or even without any lympho-depletion, which will be phenomenal for this program.

Thank you. Our next question comes from Sammy Corwin with William Blair. You may proceed.

Hey there. Congrats on making the progress this quarter. Thanks for taking my questions. I was curious what increase or difference in event-free survival Alpha-3 is powered to show. And then I noticed in your 10-K that it said that if both treatment arms look better than the control of the utility analysis, but they don't look any different than each other, that additional patients could be enrolled and analyzed. So I guess what kind of difference are you looking to see between the two treatment arms? And if they do look similar, would you pursue the lympho-depletion arm without 647? Thank you.

Yeah, Sammy, I mean, the question about the powering of the Alpha-3 study, I mean, the primary endpoint is event-free survival. We haven't gone into the specifics about the powering of the study, other than saying with the targeted about 110 patients each arm for comparison, this study is very well powered. And this also goes back to the earlier question from Mike about what could be possible at the analysis, which will happen early 2026. Yeah, we are spending some Alpha and, you know, obviously we believe that there is some possibility, you know, which may be not so small that the statistical boundary may have closed at the time. And frankly, if you look at what has happened with the CAR-T studies in the second line study, you know, whether it's the Escada Brianzi study, the sample size, number of patients that were treated in the second line study, which was comparing CAR-T with active treatment, it's around 260 to some mid-300, not so dissimilar. So those studies obviously will show the statistical significance in the mid-year. So I think that is probably some good reference to think about how Alpha-3 study may have been powered. And, you know, your second question about, you know, what we have disclosed in the 10-K, we have provided a little more guidance about how many number of patients that we'll be looking at as we start looking at the futility as well as selecting the lip for depletion. You know, here obviously if we don't see any difference, you know, there are possibilities. We may want some more patients to see whether the difference is more significant or not. Another possibility is that at the time of reviewing about 36 patient data, you know, then may provide sufficient information for us to make the lympho-depletion. You know, we will get there and this will be very much data-driven. So probably, you know, it's best that we wait to the time point rather than speculating too much.

Got it. Thank you.

Thank you. Our next question comes from Jack Allen with Baird. You may proceed.

Welcome. Thank you so much for taking the questions and congrats on the progress. I just wanted to ask about the futility analysis as well. How should we be thinking about the futility analysis as it relates to the comparison? Is it a comparison against the control arm here or is it against some sort of hurdle rate? And then on what metrics will you be looking at, you know, to evaluate futility? It would be MRD conversion, response rates, or any early survival data. Thanks so much.

Yeah, Jack, let me just take this question. You know, we get asked, you know, about the futility question. There isn't anything unique about the futility analysis that we are doing. This is a very standard thing that many, you know, phase three studies, sometimes even phase two studies will be doing. What gets looked at in the futility analysis, really the totality of the data, you know, you can look at the safety. Obviously, we want the safety to be, you know, tracking close to our expectation based on what we have seen in the Alpha 3 study. And, you know, there is a significant imbalance in the safety, you know, between the observation control arm versus two treatment arms. And then the second, you know, one is the, you know, the sort of the signs of efficacy. And here we will be relying primarily on the MRD conversion rate. So every patient who gets enrolled in Alpha 3 study starts with MRD positive, you know, both the control as you know, two treatment arms using different lympho depletion. The expectation is MRD conversion will be heavily, you know, you know, occurring more, you know, skin functioning more in the treatment arm compared to the observation. So that will be the, you know, essentially the futility that we will be looking for. Then afterwards, you know, once that futility has been crossed, we will be looking at the two treatment arms, two lympho depletion arms to see which one is better.

Thanks so much for coming.

Thank you. Our next question comes from Byron Amin with Piper Sandler. You may proceed.

Yeah. Hi, guys. Thanks for taking my question. I think, you know, for the Alpha 3, your prior guide stated that patient enrollment would complete by first half of 2026. So I just want to see if you're continuing to track towards that timeline. And then I guess second question is, I think you mentioned that the split in the trial is 50-50 between community versus academic in terms of site. How about the patient split? Is that 50-50 as well?

You know, Byron, in terms of the overall trial, you know, guidance, you know, we are now focusing more on the data readout, you know, which has not changed. And obviously, you know, your particular question around trial completion, I think we are more or less tracking around that time. And obviously, you know, as we progress with the study, you know, we'll provide, you know, more information. With respect to your second question, can you just repeat the second question?

Yeah, I think you mentioned, yeah, in terms of the trial split, the site split is 50-50 across the 40 sites that you've activated between community and academic.

Yeah, yeah, yeah. So

I want to understand the patient split similar as well.

Yeah, let me pass that question to Zach to provide more details on, you know, in terms of the site distribution across community versus academic centers.

Yeah, thanks, David, and thanks, Byron, for the question. Yes, you're correct that it's about 50-50 split right now with about four-fifths of the sites activated community versus academic. As far as the patients coming in, what I can say is that we haven't seen a heavy skew in one direction or the other. I can't say it's exactly 50-50, but what I can say is that we are seeing, you know, robust activity in both the community centers as well as the academic centers.

Great, thank you.

Thank you. Our next question comes from John Newman with Canaccord Genuity. You may proceed.

Hi, guys. Thanks for taking my question. Just wondered on the initial data for 329 at year-end 25. Just curious if you know how much follow-up you might have if you would be able to look at one month or maybe three. And then also, given the mechanism of action for 329, is there a way that you can look at not just the B cell depletion, but also potentially depletion of the active T cells?

Thanks. Yeah, John, great question. It's something that we constantly talk about internally. Let me pass off to Zach to answer the questions about the length of follow-up that we may have and what else we're going to be looking at in the biomarker analysis.

Yeah, so thanks, John. So we haven't said exactly how much follow-up we expect to have, and we have said that with the trial starting middle of this year and us obviously moving as quickly as we can, we should have a handful of patients treated hopefully by the end of the year and a little bit of follow-up. What we've guided towards in terms of proof of concept is, as David pointed out earlier, the biomarker data, so B cell depletion as well as expansion of the CAR T cell, and we'll have some early safety results too. So we can gather that information in relative short order in a clinical trial. We won't really have a significant read on durable efficacy, of course, by the end of this year. Diving into your second question on the specific analyses that we plan to conduct, so obviously B cells is a must-have, but the T cells, as we have shown in the 316 program, is going to be an area of focus as well. And what I think we've elegantly shown, such as in the CITTI data just a few months ago, is that we can really parse out the CD70 positive versus the CD70 negative cells in the patients. And really that is what has given us the foundation that has validated the dagger effect in patients. So we'll be doing very similar analyses in 329 and see whether we are seeing that evidence of a strong dagger effect in these patients.

Okay, great.

Thank you. Thank you. Our next question comes from Atasita. Good morning. With truus, you may proceed.

Hey, guys. Thanks for taking my questions and appreciate all the color today. I want to follow up John's excellent question on the resolution study. It's great to see that you guys are exploring the lympho depletion free strategy as well here. I want to ask you this. How much follow-up do you need to answer that question? And I ask because just in some of these indications you're going after the KOLs out there, like to see maybe a treatment benefit after six months or even a year. Do you think you'll need to do that all the way up to then to really answer that question of whether or not you can go with the lympho depletion free strategy? And then a second quick follow-up on the JCO publication, all the durable responses were CRs. And it also goes for to say that all six patients with low disease burden had CRs. So I'd like to confirm, are those the six patients that are the ones that are still in response on the swimmer at the data cutoff on that paper?

Thanks. Yeah, so two questions. Let me take the 329 resolution question about whether we need to follow the patient for longer. Definitely without question, we will be following these patients longer than the initial biomarker data analysis. So the way we see it is a biomarker, especially piece of depletion and cell expansion, auto-anabetic, titer changes. I think these are very great telltale signs around whether the treatment is, 329 is behaving as we have expected. And obviously, as we follow these patients, we will get more information about the clinical outcome, including if some of these patients going to complete remission, how long that may last. I mean, those are much longer follow-up and they will not be the part of the initial data release that we are projecting year end. The second question, I'll pass off to Dr. Sastry to respond.

Thanks, Asuka. So the first thing to kind of keep in mind is, as you pointed out in your question, is most important outcome after any treatment at all, whether it's CAR T cells or anything else, is that you achieve a complete remission. That is obviously the number one thing, because if you don't get to a complete remission, your chance at a durable cure is zero. So that's the first thing to keep in mind. What we showed in our subgroup analysis is that if you had low disease burden as assessed by either the tumor measurements or by the serum LDH, you had an extremely high chance of achieving that must-have clinical scenario of a complete remission. That said, we want to also tout that the semicell product itself is a very potent product. Obviously, it's very active, as the JCO paper indicated. And we actually had plenty of patients that had bulky disease that achieved durable CRs as well. So it was a little bit of mixing and matching.

Thank you. Our next question goes to Matthew Wiegler with Oppenheimer. You may proceed.

Hey guys, thanks for the question. I'll ask another one on resolution, but maybe in a slightly different way, which is hypothetically, how much efficacy are you potentially willing to leave on the table to get away with no lymphoconditioning? I.e., is no lymphoconditioning really a game changer, or is it just a nice to have, in your opinion?

Thanks. Yeah, Matthew, excellent question. You are asking things that are highly debated internally. I mean, probably the best way that I can sort of describe is lymphodepletion is a potential barrier. And if you can lower the lymphodepletion, that's a big plus. And if you can eliminate, that's really a big, big game changer. But frankly, probably the best way to think about is when it doesn't require, it doesn't have the burden of lymphodepletion, it can be used more widely. So it really creates the potential to treat not only autoimmune disorders with high severity, but also moderate severity. So it gives a lot more opportunity to address different patients. So, yeah, we would love to have no lymphodepletion, but I think even just lowering the lymphodepletion would be a significant win for the 329 program.

Appreciate it. Thank you. Our next question comes from Luca Issi with RBC Capital Markets. You may proceed.

Hey, guys, this is Shelby on for Luca, and thanks for taking the question. On Alpha 3, it's our understanding that there is an option for inpatient or outpatient treatment. Is that decision left up to the investigator? And how should we think about the mix of patients who will be treated outpatient versus inpatient? Any color there, much appreciated.

Thanks. And Shelby, I'm going to ask Zach to respond to your question. Zach? Yep.

Thanks, David and Shelby. So indeed, there is no requirement at all for inpatient, either LD or cell administration. It is entirely up to the investigator on a -by-case basis. I will say that we are seeing, as we've seen for a long time in our semicell programs, even in the Alpha and Alpha 2, we are seeing a significant number of these patients being treated fully as outpatient. And of course, that is the vision. Part of the vision for this product is that it's going to be easy to administer in the clinical settings where these patients receive frontline care. As for specific characteristics that would lead to a patient being treated inpatient versus outpatient, there's a host of them. I won't go into them now, but one of the great benefits of the Alpha 3 study is that all of these patients are going to be in remission when they receive their semicell and their lymphodipletion. And as David pointed out earlier in the call, patients with low disease burden tend to have better safety outcomes than those with high disease burden. So on balance, we would expect a significantly greater fraction of these patients over the duration of the study to be managed as fully as outpatients. And that is our expectation.

And also, if I can add one comment to that response, Shelby, I think the important thing is that in Alpha 3 study, we do not require hospitalization. And in that way, in essence, what that's doing is this trial is just like any other trial. And whether physician does with that information, whether they decide to treat as a fully outpatient or maybe put them in the hospital for a day or two, that's essentially how the practice is done, not just in the cell therapy, but in any other cancer treatment. So it's really giving the patient and the physicians the option on how they want to receive the investigation of therapy in the Alpha 3 study.

Thank you. Our next question comes from Samantha Seminka with Citi. You may proceed.

Hi. Good afternoon. Thanks very much for taking the question. Some of your autologous CAR-T counterparts have spoken about a push to expand into large community oncology centers that could potentially overlap with your Alpha 3 trial sites. So I'm wondering, to what extent are you seeing this infrastructure being built at the community centers you interact with? How much of this work do you think could be in place by the time you potentially launch the MSL? And how are you thinking about your ability to leverage this infrastructure for the launch? Thanks very much.

Samantha, excellent question. I think the effort, not just by us, but also in the entire CAR-T community to move into the sort of community-based cancer centers, I think that's just going to expand and expand the usage of CAR-T. I mean, that's a very important aspect of any product launch and product life cycle management. I think in many ways, here is where the Allergen A CAR-T really plays favorably. I mean, not having the logistical challenge, just being able to ship the product when the patient needs the treatment. And also in our case, as we're learning, as we improve the manufacturing, the scalability of the manufacturing, all these things playing in our favor. So as the effort from the Autalis CAR-T companies to expand their use into the community cancer centers, we see that as a positive thing for the field. And we also see as a positive thing for what we are doing with the Alpha-3 study.

Thank you. Our next question comes from Ben Bernet with Stiefel. You may proceed.

Hi, this is Catalina Ivanes-Ventozon for Ben. Thank you for taking our questions. First, the interim analysis of stem cell in mid-2025, can you remind us when you are measuring the MRT conversion? Is it at one month post-stem cell infusion or later? And I have a follow-up.

Yeah, we're trying to limit the questions to one. Zach, you want to take the question about the timing of the MRT test?

Yeah, thanks Catalina. We have not disclosed exactly the timing of that draw. And as David pointed out earlier, of course, there'll be other elements that we're assessing to make that lympho-depletion decision in addition to the MRT conversion.

Okay, understood. Thank you.

Thank you. Our next question comes from Laura Prendergrass with Wayman James. You may proceed.

Hey guys, can you elaborate a bit more on the registrational path for the foresight MRD test and how it relates to the registrational path for stem cell in 1L lymphoma? Thanks.

Hey, Zach, do you want to take that question?

Yeah, that'll be an easy one. Thanks, Laura. I, you know, we, the plan has been all along to have a concurrent launch of these products at the time of the FDA approval. The specifics around the path to registration of the MRD test, though I would refer you to the foresight management.

But you don't foresee it being an issue at all with getting semisol approved in 1L?

No.

Got it. Thanks.

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

All right. Thank you. I just want to reiterate, you know, Allergen entered 2024 with a bold strategy. And today we stand on the brink of a transformative year. With three pioneering programs, each approaching critical milestones, we are proving that Allergen A CAR-T has the potential to redefine patient care. So thank you for your ongoing belief in Allergen and the field of cell therapy. Operator, you may now 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.