Q4 2025 Allogene Therapeutics Inc Earnings Call

March 12, 2026

Operator 2: Hello, and thank you for standing by. Welcome to Allogene Therapeutics Q4 2025 Conference Call. After the speaker's presentation, there'll be a Q&A session. To ask a question during the session, you need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be aware that today's conference call is being recorded. I would now like to turn the call over to Christine Cassiano, Chief Corporate Affairs and Brand Strategy Officer. Ms. Cassiano, please go ahead.

Speaker #1: You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. Please be aware that today's conference call is being recorded.

Speaker #1: 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 welcome everyone to Allogene's conference call.

Christine Cassiano: Thank you, operator, and welcome everyone to Allogene's conference call. After the market closed, Allogene issued a press release that provided a business update and financial results for the Q4 and year-end 2025. This press release and today's webcast are available on our website. Following our prepared remarks, we will host a Q&A session and we'll aim to keep the 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 Geoffrey Parker, Chief Financial Officer. During today's call, we will be making certain forward-looking statements.

Speaker #1: After the market closed, Allogene issued a press release that provided a business update and financial results for the fourth quarter and year-end 2025. This press release and today's webcast are available on our website.

Speaker #1: Following our prepared remarks, we will host a Q&A session and will aim to keep the 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 Geoff Parker, Chief Financial Officer.

Christine Cassiano: Following our prepared remarks, we will host a Q&A session and we'll aim to keep the 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 Geoff Parker, Chief Financial Officer. During today's call, we will be making certain forward-looking statements.

Speaker #1: 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 forecast, and financial guidance, among other things.

Christine Cassiano: 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. 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.

Speaker #1: 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.

Christine Cassiano: A description of potential risks can be found in our 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.

Speaker #1: Your caution 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.

Speaker #1: Thank you, Christine. As we close 2025 and enter what we expect to be a defining year for Allogene, the environment around us is shifting.

David Chang: Thank you, Christine. As we close 2025 and enter what we expect to be a defining year for Allogene, the environment around us is shifting. Cell therapy has entered a phase defined by evidence where progress will be measured not by speculation and promises, but by data and disciplined execution. That shift plays to our strength. Our focus in 2026 is straightforward. Delivering meaningful clinical milestones with rigor and speed. This is a year of critical proof points. Proof points that could validate our allogeneic platform, not merely as an alternative, but as the imperative path to making cell therapy scalable, accessible, and deliverable at biologic-like scale. First, with cema-cel and ALPHA3, we are asking a bold but important question that could redefine the management of large B-cell lymphoma.

Speaker #1: Cell therapy has entered a phase defined by evidence, where progress will be measured not by speculation and promises but by data and disciplined execution.

Speaker #1: That shift plays to our strength. Our focus in 2026 is straightforward: delivering meaningful clinical milestones with rigor and speed. This is a year of critical proof points, proof points that could validate our allogeneic platform not merely as an alternative but as the imperative path to making cell therapy scalable, accessible, and deliverable at biologic-like scale.

David Chang: This is a year of critical proof points. Proof points that could validate our allogeneic platform, not merely as an alternative, but as the imperative path to making cell therapy scalable, accessible, and deliverable at biologic-like scale. First, with cema-cel and ALPHA3, we are asking a bold but important question that could redefine the management of large B-cell lymphoma.

Speaker #1: First, with stem cell in Alpha 3, we are asking a bold but important question that could redefine the management of large B-cell lymphoma. Can we intervene earlier?

David Chang: Can we intervene earlier, making CAR T truly accessible in the community setting, meaningfully improve outcomes, and alter the course of disease without disrupting the physician's practice? The goals of this study are not about incremental improvement in our late-line setting. It is about shifting the paradigm in the first-line treatment and demonstrating that cema-cel can reduce the risk of relapse and improve the cure rate. Importantly, it is about expanding access to community cancer centers that historically have been excluded from offering CAR T, bringing advanced cell therapy to where most patients are treated off-the-shelf at biologic-like scale. Second, with ALLO-329, we are extending the promise of allogeneic cell therapy to autoimmune disease. ALLO-329 is a purpose-built dual CD19, CD70 CAR design specifically for immune-mediated conditions, incorporating our Dagger technology to potentially reduce or maybe eliminate traditional lymphodepletion.

Speaker #1: Making CAR-T truly accessible in the community setting, meaningfully improve outcomes, and alter the course of disease without disrupting the physician's practice? The goals of this study are not about incremental improvement in our late-line setting.

Speaker #1: It is about shifting the paradigm in the first-line treatment and demonstrating that stem cell can reduce the risk of relapse and improve the cure rate.

David Chang: Importantly, it is about expanding access to community cancer centers that historically have been excluded from offering CAR T, bringing advanced cell therapy to where most patients are treated off-the-shelf at biologic-like scale. Second, with ALLO-329, we are extending the promise of allogeneic cell therapy to autoimmune disease. ALLO-329 is a purpose-built dual CD19, CD70 CAR design specifically for immune-mediated conditions, incorporating our Dagger technology to potentially reduce or maybe eliminate traditional lymphodepletion.

Speaker #1: Importantly, it is about expanding access to community cancer centers that historically have been excluded from offering CAR-T, bringing advanced cell therapy to our most patients that are treated.

Speaker #1: Off-the-shelf at biologic-like scale. Second, with Allo 329, we are extending the promise of allogeneic cell therapy to autoimmune disease. Allo 329 is a purpose-built dual CD19/CD70 CAR design specifically for immune-mediated conditions, incorporating our dagger technology to potentially reduce or maybe eliminate traditional lymphodepletion.

Speaker #1: We expect to report proof of concept data in June 2026 and assuming continued progress, another clinical update, by the end of the year. We are entering this execution-focused period from a position of financial strength, having extended our runway into the first quarter of 2028.

David Chang: We expect to report proof-of-concept data in June 2026, and assuming continued progress, another clinical update by the end of the year. We are entering this execution focus period from a position of financial strength, having extended our runway into Q1 2028. That gives us the ability to advance ALPHA3 and RESOLUTION with focus and discipline. We have built a broad and innovative clinical pipeline, but we recognize we cannot advance everything at once. Discipline requires prioritization. Today, we are concentrating our resources on the programs where allogeneic CAR T has the greatest potential to demonstrate what this modality can achieve when developed around its inherent advantages, scalability, accessibility, and ultimately, the potential for durable cure.

Speaker #1: That gives us the ability to advance Alpha 3 and resolution with focus and discipline. We have built a broad and innovative clinical pipeline, but we recognize we cannot advance everything at once.

Speaker #1: Discipline requires prioritization. Today, we are concentrating our resources on the programs where allogeneic CAR-T has the greatest potential to demonstrate what this modality can achieve when developed around its inherent advantages.

David Chang: Today, we are concentrating our resources on the programs where allogeneic CAR T has the greatest potential to demonstrate what this modality can achieve when developed around its inherent advantages, scalability, accessibility, and ultimately, the potential for durable cure. At the same time, we believe that as the field recognizes that allogeneic CAR T can deliver at scale with rigor and practicality, it will unlock new opportunities to expand the platform into additional settings and indications. With that, I will turn it over to Zach to walk through the clinical progress in more detail.

Speaker #1: Scalability, accessibility, and ultimately, the potential for durable cure. At the same time, we believe that as the field recognizes that allogeneic CAR-T can deliver at scale with rigor and practicality, it will unlock new opportunities to expand the platform into additional settings and indications.

David Chang: At the same time, we believe that as the field recognizes that allogeneic CAR T can deliver at scale with rigor and practicality, it will unlock new opportunities to expand the platform into additional settings and indications. With that, I will turn it over to Zach to walk through the clinical progress in more detail.

Speaker #1: With that, I will turn it over to Zach to walk through the clinical progress in more detail. Thanks, David. As David outlined, the second quarter is defined by two key programs: stem cell in Alpha 3 and Allo 329 in resolution.

Zachary Roberts: Thanks, David. As David outlined, Q2 is defined by two key programs, cema-cel, ALPHA3, and ALLO-329 in RESOLUTION. I'll concentrate on the clinical execution behind these studies and what we expect to learn in the months ahead, beginning with ALPHA3. ALPHA3 is the first randomized study in lymphoma designed to test whether early MRD guided consolidation with an allogeneic CAR T can prevent relapse. Patients who achieve remission after standard first-line therapy undergo highly sensitive ctDNA testing. Those who are MRD positive and therefore at high risk of relapse, are randomized to observation or treatment with cema-cel. In April, we plan to report results from the interim futility analysis evaluating MRD clearance in 24 patients, 12 each in the cema-cel-treated arm and the control observation arm, along with early safety data. We will also outline the anticipated timeline and key inflection points as the study progresses.

Speaker #1: Our concentrate on the clinical execution behind these studies and what we expect to learn in the months ahead, beginning with Alpha 3. Alpha 3 is the first randomized study in lymphoma designed to test whether early MRD-guided consolidation with an allogeneic CAR-T can prevent relapse.

Speaker #1: Patients who achieve remission after standard first-line therapy undergo highly sensitive ctDNA testing. Those who are MRD positive and therefore at high risk of relapse are randomized to observation or treatment with stem cell.

Zachary Roberts: Those who are MRD positive and therefore at high risk of relapse, are randomized to observation or treatment with cema-cel. In April, we plan to report results from the interim futility analysis evaluating MRD clearance in 24 patients, 12 each in the cema-cel-treated arm and the control observation arm, along with early safety data. We will also outline the anticipated timeline and key inflection points as the study progresses.

Speaker #1: In April, we plan to report results from the interim futility analysis evaluating MRD clearance in 24 patients, 12 each in the stem cell-treated arm and the control observation arm, along with early safety data.

Speaker #1: We will also outline the anticipated timeline and key inflection points as the study progresses. We've anchored expectations around what we and many clinicians believe would be a meaningful threshold at 25 to 30 percent absolute delta in MRD clearance between arms.

Zachary Roberts: We've anchored expectations around what we and many clinicians believe would be a meaningful threshold at 25% to 30% absolute delta in MRD clearance between arms. Achieving that outcome would have the potential to alter disease trajectory and meaningfully improve the rate of cure of large B-cell lymphoma in the first-line setting. At the upcoming analysis, we also intend to provide preliminary safety data and additional perspective on how the use of cema-cel is being implemented in community settings. We now have over 60 active sites across the US and Canada, with engagement with health authorities and clinical site startup activities underway in Australia and South Korea.

Speaker #1: Achieving that outcome would have the potential to alter disease trajectory and meaningfully improve the rate of cure of large B-cell lymphoma in the first-line setting.

Speaker #1: At the upcoming analysis, we also intend to provide preliminary safety data and additional perspective on how the use of stem cell is being implemented in community settings.

Zachary Roberts: At the upcoming analysis, we also intend to provide preliminary safety data and additional perspective on how the use of cema-cel is being implemented in community settings. We now have over 60 active sites across the US and Canada, with engagement with health authorities and clinical site startup activities underway in Australia and South Korea.

Speaker #1: We now have over 60 active sites across the U.S. and Canada, with engagement with health authorities and clinical site startup activities underway in Australia and South Korea.

Speaker #1: The level of real-world integration of stem cell as consolidation into routine practice across both academic and community centers underscores what we believe is a core advantage of the off-the-shelf model and its potential to expand access beyond traditional CAR-T delivery hubs.

Zachary Roberts: The level of real-world integration of cema-cel as consolidation into routine practice across both academic and community centers underscores what we believe is a core advantage of the off-the-shelf model and its potential to expand access beyond traditional CAR T delivery hubs. I'll now spend a few minutes on ALLO-329, our first in class dual CD19, CD70 allogeneic CAR T therapy designed specifically for autoimmune disease. ALLO-329 was engineered for this setting from the outset. It targets CD19 positive B cells and CD70 positive activated T cells, both of which contribute to autoimmune disease. Our Dagger technology is designed to endow the cells with a kind of built-in lymphodepletion to enable optimal cell expansion and persistence while potentially reducing or eliminating the need for conventional cytotoxic lymphodepletion.

Speaker #1: I'll now spend a few minutes on Allo 329, our first-in-class dual cd19/cd70 allogeneic CAR-T therapy designed specifically for autoimmune disease. Allo 329 was engineered for this setting from the outset.

Speaker #1: It targets cd19-positive B cells and cd70-positive activated T cells both of which contribute to autoimmune disease. Our dagger technology is designed to endow the cells with a kind of built-in lymphodepletion to enable optimal cell expansion and persistence while potentially reducing or eliminating the need for conventional cytotoxic lymphodepletion.

Zachary Roberts: Our Dagger technology is designed to endow the cells with a kind of built-in lymphodepletion to enable optimal cell expansion and persistence while potentially reducing or eliminating the need for conventional cytotoxic lymphodepletion.

Speaker #1: The Phase One RESOLUTION trial is a three-plus-three dose escalation study enrolling patients across multiple rheumatology indications, including systemic lupus erythematosus, lupus nephritis, scleroderma, and inflammatory myositis.

Zachary Roberts: The Phase 1 RESOLUTION trial is a 3 + 3 dose escalation study enrolling patients across multiple rheumatology indications, including systemic lupus erythematosus, lupus nephritis, scleroderma, and inflammatory myositis. The study is evaluating several dose levels, beginning at 20 million CAR T cells in two parallel dose escalation cohorts, one that includes cyclophosphamide only and one without any traditional lymphodepletion. 20 million cells is a small number, but one that we selected based on our conviction that the Dagger technology in ALLO-329 could drive meaningful in vivo expansion. For context, competitive programs in autoimmune disease are evaluating doses of autologous CAR T cells that are up to 5 to 10 times higher than our starting dose, and other allogeneic cell therapy programs are exploring cell doses nearly 50 times higher.

Speaker #1: The study is evaluating several dose levels beginning at 20 million CAR-T cells in two parallel dose escalation cohorts, one that includes cyclophosphamide only and one without any traditional lymphodepletion.

Speaker #1: Twenty million cells is a small number, but one that we selected based on our conviction that the Dagger technology in ALLO-329 could drive meaningful in vivo expansion.

Speaker #1: For context, competitive programs in autoimmune disease are evaluating doses of autologous CAR-T cells that are up to 5 to 10 times higher than our starting dose and other allogeneic cell therapy programs are exploring cell doses nearly 50 times higher.

Zachary Roberts: For context, competitive programs in autoimmune disease are evaluating doses of autologous CAR T cells that are up to 5 to 10 times higher than our starting dose, and other allogeneic cell therapy programs are exploring cell doses nearly 50 times higher.

Speaker #1: In June of this year, we expect to report initial proof of concept translational data as well as early clinical signals from the first dosing cohort with and without lymphodepletion.

Zachary Roberts: In June of this year, we expect to report initial proof of concept translational data as well as early clinical signals from the first dosing cohort with and without lymphodepletion. As an off-the-shelf allogeneic CAR T product that does not require any degree of patient HLA matching, ALLO-329 persistence in patients treated with minimal or no lymphodepletion at this low starting cell dose would be a strong validation of the Dagger effect in autoimmune patients. Assuming continued enrollment and follow-up, we anticipate providing an additional clinical update later this year. The opportunity in autoimmune disease could be significant, but success in this space requires tolerability, outpatient feasibility, and scalability, particularly as treatment moves into rheumatology practices. ALLO-329 was engineered with those requirements in mind.

Speaker #1: As an off-the-shelf allogeneic CAR-T product that does not require any degree of patient HLA matching, ALLO-329 persistence in patients treated with minimal or no lymphodepletion at this low starting cell dose would be a strong validation of the Dagger effect in autoimmune patients.

Speaker #1: Assuming continued enrollment and follow-up, we anticipate providing an additional clinical update later this year. The opportunity in autoimmune disease could be significant, but success in this space requires tolerability, outpatient feasibility, and scalability particularly as treatment moves into rheumatology practices.

Zachary Roberts: The opportunity in autoimmune disease could be significant, but success in this space requires tolerability, outpatient feasibility, and scalability, particularly as treatment moves into rheumatology practices. ALLO-329 was engineered with those requirements in mind. Across both programs, our focus remains on disciplined execution with the goal of generating data that clearly define the role of allogeneic CAR T in earlier line oncology and in autoimmune disease. With that, I'll turn the call over to Geoff.

Speaker #1: ALLO-329 was engineered with those requirements in mind. Across both programs, our focus remains on disciplined execution with the goal of generating data that clearly define the role of allogeneic CAR-T in earlier-line oncology and in autoimmune disease.

Zachary Roberts: Across both programs, our focus remains on disciplined execution with the goal of generating data that clearly define the role of allogeneic CAR T in earlier line oncology and in autoimmune disease. With that, I'll turn the call over to Jeff.

Speaker #1: With that, I'll turn the call over to Jeff. Thank you, Zach. As we prepare for multiple clinical catalysts in 2026, our financial position is aligned with our strategic priorities.

Geoffrey Parker: Thank you, Zach. As we prepare for multiple clinical catalysts in 2026, our financial position is aligned with our strategic priorities. We have been deliberate in concentrating our resources behind ALPHA3 and RESOLUTION while maintaining balance sheet strength and operational flexibility. As of 31 December 2025, we had $258.3 million in cash equivalents, and investments. In February of this year, we received an additional $23.7 million previously held in escrow related to Servier's favorable arbitration outcome with Cellectis. We have also made prudent and opportunistic use of our ATM equity facility and have raised an additional $20.7 million year to date.

Geoff Parker: Thank you, Zach. As we prepare for multiple clinical catalysts in 2026, our financial position is aligned with our strategic priorities. We have been deliberate in concentrating our resources behind ALPHA3 and RESOLUTION while maintaining balance sheet strength and operational flexibility. As of 31 December 2025, we had $258.3 million in cash equivalents, and investments.

Speaker #1: We have been deliberate in concentrating our resources behind Alpha 3 and resolution while maintaining balance sheet strength and operational flexibility. As of December 31, 2025, we had $258.3 million in cash, cash equivalents, and investments.

Speaker #1: In February, of this year, we received an additional $23.7 million previously held in escrow related to Servier's favorable arbitration outcome with Selectis. We have also made prudent and opportunistic use of our ATM equity facility and have raised an additional $20.7 million year to date.

Geoff Parker: In February of this year, we received an additional $23.7 million previously held in escrow related to Servier's favorable arbitration outcome with Cellectis. We have also made prudent and opportunistic use of our ATM equity facility and have raised an additional $20.7 million year to date.

Speaker #1: As a result of these actions, we have extended our cash runway into the first quarter of 2028, which we believe covers the timeframe we currently estimate is needed to complete enrollment in the Alpha 3 trial.

Geoffrey Parker: As a result of these actions, we have extended our cash runway into Q1 2028, which we believe covers the timeframe we currently estimate is needed to complete enrollment in the ALPHA3 trial. R&D expenses for Q4 were $28.6 million, including $2.5 million of non-cash stock-based compensation. For the full year 2025, research and development expenses were $150.2 million, which includes $12.9 million of non-cash stock-based compensation expense. G&A expenses for Q4 2025 were $13.8 million, including $5.6 million in non-cash stock-based compensation. For the full year 2025, G&A expenses were $56.8 million, which includes $24.7 million of non-cash stock-based compensation expense.

Geoff Parker: As a result of these actions, we have extended our cash runway into Q1 2028, which we believe covers the timeframe we currently estimate is needed to complete enrollment in the ALPHA3 trial. R&D expenses for Q4 were $28.6 million, including $2.5 million of non-cash stock-based compensation. For the full year 2025, research and development expenses were $150.2 million, which includes $12.9 million of non-cash stock-based compensation expense.

Speaker #1: R&D expenses for the fourth quarter were $28.6 million, including $2.5 million of non-cash stock-based compensation. For the full year of 2025, research and development expenses were $150.2 million, which includes $12.9 million of non-cash stock-based compensation expense.

Speaker #1: GNA expenses for Q4 2025 were $13.8 million, including $5.6 million in non-cash stock-based compensation. For the full year 2025, GNA expenses were $56.8 million, which includes $24.7 million of non-cash stock-based compensation expense.

Geoff Parker: G&A expenses for Q4 2025 were $13.8 million, including $5.6 million in non-cash stock-based compensation. For the full year 2025, G&A expenses were $56.8 million, which includes $24.7 million of non-cash stock-based compensation expense.

Speaker #1: Net loss for the fourth quarter was $38.8 million, or $17 cents per share, including non-cash stock-based compensation expense of $8.1 million. For the full year of 2025, net loss was $190.9 million, or $87 cents per share, including non-cash stock-based compensation expense of $37.6 million.

Geoffrey Parker: Net loss for the Q4 was $38.8 million, or $0.17 per share, including non-cash stock-based compensation expense of $8.1 million. For the full year of 2025, net loss was $190.9 million, or $0.87 per share, including non-cash stock-based compensation expense of $37.6 million and non-cash retirement of long-lived asset expense of $2.4 million. Guidance for operating cash expense in 2026 is expected to be approximately $150 million. GAAP operating expenses are expected to be approximately $210 million, including estimated non-cash stock-based compensation expense of approximately $35 million. These estimates exclude any impact from potential business development activities.

Geoff Parker: Net loss for the Q4 was $38.8 million, or $0.17 per share, including non-cash stock-based compensation expense of $8.1 million. For the full year of 2025, net loss was $190.9 million, or $0.87 per share, including non-cash stock-based compensation expense of $37.6 million and non-cash retirement of long-lived asset expense of $2.4 million. Guidance for operating cash expense in 2026 is expected to be approximately $150 million.

Speaker #1: And non-cash impairment of long-lived asset expense of $2.4 million. Guidance for operating cash expense in 2026 is expected to be approximately $150 million. GAAP operating expenses are expected to be approximately $210 million, including estimated non-cash stock-based compensation expense of approximately $35 million.

Geoff Parker: GAAP operating expenses are expected to be approximately $210 million, including estimated non-cash stock-based compensation expense of approximately $35 million. These estimates exclude any impact from potential business development activities.

Speaker #1: These estimates exclude any impact from potential business development activities. With pivotal data from Alpha 3 approaching in April, proof of concept data for Allo 329 expected in June, and cash runway now extended into 2028, we believe we are well capitalized to execute through these important inflection points.

Geoffrey Parker: With pivotal data from ALPHA3 approaching in April, proof of concept data for ALLO-329 expected in June, and cash runway now extended into 2028, we believe we are well capitalized to execute through these important inflection points. Our focus remains clear. Advance high impact programs, manage capital responsibly, and position Allogene for long-term value creation. We'll now open the call for questions.

Geoff Parker: With pivotal data from ALPHA3 approaching in April, proof of concept data for ALLO-329 expected in June, and cash runway now extended into 2028, we believe we are well capitalized to execute through these important inflection points. Our focus remains clear. Advance high impact programs, manage capital responsibly, and position Allogene for long-term value creation. We'll now open the call for questions.

Speaker #1: Our focus remains clear: advance high-impact programs manage capital responsibly and position Allogene for long-term value creation. We'll now open the call for questions.

Speaker #2: Thank you, ladies and gentlemen. If you have a question or a comment at this time, please press star 11 on your telephone. If your question has been answered and you wish to move yourself from the queue, please press star 11 again.

Operator 2: Thank you. Ladies and gentlemen, if you have a question or a comment at this time, please press star one one on your telephone. If your question has been answered or you wish to move yourself from the queue, please press star one one again. We'll pause for a moment while we compile our Q&A roster. Our first question comes from Tyler Van Buren with TD Cowen. Your line is open.

Operator: Thank you. Ladies and gentlemen, if you have a question or a comment at this time, please press star one one on your telephone. If your question has been answered or you wish to move yourself from the queue, please press star one one again. We'll pause for a moment while we compile our Q&A roster. Our first question comes from Tyler Van Buren with TD Cowen. Your line is open.

Speaker #2: We'll pause for a moment while we compile our Q&A roster. Our first question comes from Tyler Van Buren with TD Cowen. Your line is open.

Speaker #3: Hey, guys. Thanks for taking the question and looking forward to both data updates next quarter. Can you elaborate on the safety parameters you'll be looking at with the Alpha 3 data update next month and what the bar is to support broad uptake in the community setting and perhaps more importantly, how investigators in the community setting have already responded to incorporating seamless cell as a seventh cycle of treatment in the front line?

Tyler Van Buren: Hey, guys. Thanks for taking the question and looking forward to both data updates next quarter. Can you elaborate on the safety parameters you'll be looking at with the ALPHA3 data update next month? What the bar is to support broad uptake in the community setting? Perhaps more importantly, how investigators in the community setting have already responded to incorporating cema-cel as a seventh cycle of treatment in the front line.

Zachary Roberts: Tyler, thank you very much. I'll

David Chang: Tyler, thank you very much. Our CMO, Zach, to elaborate on safety aspect.

Speaker #4: Tyler, thank you very much. I'll ask our CMO, Zach, to elaborate on safety aspect.

David Chang: Our CMO, Zach, to elaborate on safety aspect.

Zachary Roberts: Hey, Tyler, thanks for the question. So we plan to provide some high-level safety information, enough for everybody to understand how well this is being tolerated. It's unlikely we'll go into, you know, very, very minute detail, but certainly serious adverse events in both arms, you know, the sorts of adverse events that would lead to hospitalization, those sorts of things, which absolutely kind of feeds into your second and third questions. What is the bar that we need to hit for safety? We believe that this is best delivered as an outpatient, so therefore, this needs to be a therapy that can be delivered as an outpatient. It does not lead to rehospitalization due to adverse events. Finally, you know, can this be done in the community and absolutely in the community it's being done currently.

Zachary Roberts: Hey, Tyler, thanks for the question. So, we plan to provide some high-level safety information, enough for everybody to understand how well this is being tolerated. It's unlikely we'll go into, you know, very, very minute detail, but certainly serious adverse events in both arms, you know, the sorts of adverse events that would lead to hospitalization, those sorts of things, which absolutely kind of feeds into your second and third questions. What is the bar that we need to hit for safety?

Speaker #5: Hey, Tyler. Thanks for the question. So we plan to provide some high-level safety information, enough for everybody to understand how well this is being tolerated.

Speaker #5: It unlikely will go into very, very minute detail, but certainly serious adverse events in both arms these sorts of adverse events that would lead to hospitalization, those sorts of things, which absolutely kind of feeds into your second and third that we need to hit for safety?

Speaker #5: We believe that this is best delivered as an outpatient. So therefore, this needs to be a therapy that can be delivered as an outpatient.

Zachary Roberts: We believe that this is best delivered as an outpatient, so therefore, this needs to be a therapy that can be delivered as an outpatient. It does not lead to rehospitalization due to adverse events. Finally, you know, can this be done in the community and absolutely in the community it's being done currently.We look forward to sharing all of the safety aspects that are allowing this to be taken up in the community by physicians.

Speaker #5: It does not lead to rehospitalization due to adverse events. And finally, can this be done in the community? Absolutely—in the community, it's being done currently.

Zachary Roberts: We look forward to sharing all of the safety aspects that are allowing this to be taken up in the community by physicians.

Speaker #5: And we look forward to sharing all of the safety aspects that are allowing this to be taken up in the community by physicians.

Speaker #2: Thank you. One moment for our next question. Our next question comes from Byron Amin with Piper Sandler. Your line is open.

Operator 1: Thank you. One moment for our next question. Our next question comes from Biren Amin with Piper Sandler. Your line is open.

Operator: Thank you. One moment for our next question. Our next question comes from Biren Amin with Piper Sandler. Your line is open.

Biren Amin: Yeah. Hi, guys. Thanks for taking my questions. I wanted to focus on the recent ZUMA-7 MRD analysis that were published last month, where axicabtagene ciloleucel observed a treatment difference of 20% on MRD negative, which, you know, translates to about an EFS benefit of around 27 months versus the control group. Given you're expecting a 25% to 30% difference on MRD conversion, what read-throughs do you have from the ZUMA-7 data and your confidence on stopping at your interim EFS analysis? On the interim EFS analysis, if you could maybe just walk us through how many events do you need and what assumptions on hazard ratio could lead to an early stoppage. Lastly, you know, when can we expect interim EFS data? Thank you.

Speaker #6: Yeah. Hi, guys. Thanks for taking my questions. I wanted to focus on the recent Zuma 7 MRD analysis that were published last month, where AxisL observed a treatment deference of 20% on MRD negative, which translates to about an EFS benefit of around 27 months versus the control group.

Speaker #6: Given you're expecting a 25% to 30% difference on MRD conversion, what read-throughs do you have from the ZUMA-7 data, and what's your confidence on stopping at your interim EFS analysis?

Speaker #6: And on that interim EFS analysis, if you could maybe just walk us through how many events you need, and what assumptions on hazard ratio could lead to an early stoppage?

Biren Amin: On the interim EFS analysis, if you could maybe just walk us through how many events do you need and what assumptions on hazard ratio could lead to an early stoppage. Lastly, you know, when can we expect interim EFS data? Thank you.

Speaker #6: And lastly, when can we expect interim EFS data? Thank you.

Speaker #1: Hey, Byron. Thanks for pointing out on that recent MRD data analysis coming from subgroup patients who were involved in the Zuma 7 study. We view this study to be very consistent with how we've been looking at the MRD clearance and its correlation to the clinical outcome.

David Chang: Hey, Biren. Thanks for pointing out on that recent MRD data analysis coming from subgroup of patients who are involved in the ZUMA-7 study. We view this study to be very consistent, you know, with how we've been, you know, looking at the MRD clearance and its correlation to the clinical outcome. Besides this study, an earlier study that we have been talking about is in BIG 1-11 study, where MRD clearance difference of 11% led to a very meaningful clinical difference. What has been reported with ZUMA-7 is very consistent, and I believe it sort of validates the guidance that we have been providing, which is 25% to 30% MRD clearance difference at the futility interim analysis that we project to share in April.

Speaker #1: Besides this study, the earlier study that we have been talking about is the InVigor-11 study, where an MRD clearance difference of 11% led to a very meaningful clinical difference.

Speaker #1: So what has been reported with Zuma 7 is very consistent and I believe it's sort of validates the guidance that we have been providing, which is 25 to 30 percent MRD clearance difference at the futility interim analysis that we project to share in April.

David Chang: What has been reported with ZUMA-7 is very consistent, and I believe it sort of validates the guidance that we have been providing, which is 25% to 30% MRD clearance difference at the futility interim analysis that we project to share in April.

Speaker #1: So this is highly consistent, and we do believe that 25 to 30 percent is going to translate to a very meaningful clinical difference in the outcome.

David Chang: This is highly consistent, and we do believe that 25% to 30% is gonna translate to very meaningful clinical difference in the, in the outcome. You know, with respect to your second question, you know, how much can we sort of, you know, speculate or model out about what this, you know, how the MRD clearance may translate to the, you know, EFS interim analysis? You know, I would say, you know, it just, you know, involves too many assumptions and speculations, and it's a little bit too early to talk about it. But internally, we're constantly, you know, reviewing the data and modifying our assumptions. Stay tuned.

Speaker #1: So with respect to your second question, how much can we sort of speculate or model out about what this how the MRD clearance may translate to the EFS interim analysis?

Speaker #1: I would say it just involves too many assumptions and speculations, and it's a little bit too early to talk about it. But internally, we're constantly reviewing the data and modifying our assumptions.

Speaker #1: So stay tuned.

Speaker #6: Great. Thank you.

Biren Amin: Great. Thank you.

Speaker #2: One moment for our next question. Our next question comes from Michael Yee with UBS. Your line is open.

Operator 1: One moment for our next question. Our next question comes from Michael Yee with UBS. Your line is open.

Operator: One moment for our next question. Our next question comes from Michael Yee with UBS. Your line is open.

Michael Yee: Thanks, guys. We have two questions. One was your thinking. The first question is your thinking around the interim analysis and what would define whether you took that interim analysis on EFS. In other words, if the MRD conversion is super high, is that what would drive your thinking to take the EFS? That is the question number one. Question number two is on autoimmune, and we wanted to understand the target product when you get your data coming up. Is this to be a low lymphodepletion, a no lymphodepletion type program? What are you trying to envision with the profile of that product? Thank you.

Speaker #3: We have two questions. One, was your thinking the first question is your thinking around the interim analysis and what would define whether you took that interim analysis on EFS?

Speaker #3: In other words, if the MRD conversion is super high, is that what would drive your thinking to take the EFS? So that is question number one.

Speaker #3: And then question number two is on autoimmune. And we wanted to understand the target product when you get your data coming up. Is this to be a low lymphodepletion, a no lymphodepletion type program?

Speaker #3: What are you trying to envision with the profile of that product? Thank you.

Speaker #1: Yeah. So, two great questions. In terms of—this is somewhat similar to what Byron was trying to get at. I mean, one thing is that there is enough data out there to see how MRD clearance, the relationship between that and clinical outcomes such as event-free survival, whether this is a linear relationship—meaning that if there is a greater difference in the MRD clearance, there will be a greater difference in the clinical outcome.

David Chang: Yeah, you know, two great questions. In terms of, you know, this is, you know, somewhat similar to what Biren was trying to get. You know, I mean, one thing is that there isn't enough data out there to see, you know, how MRD clearance, the relationship between that and clinical outcomes such as event-free survival. Whether this is a linear relationship, meaning that if there is a greater difference in the MRD clearance, there will be greater difference in the, you know, clinical outcome.

David Chang: That kind of data, while plausible, you know, is, you know, there is such paucity of the data, so we can't really establish the relationship other than saying, "Well, it is possible that, you know, if we see greater MRD clearance, difference, that may translate to, greater, you know, clinical benefit." You know, I get to the point about, you know, how that may sort of, you know, put us in the time of interim EFS analysis. I mean, interim EFS analysis is alpha spending analysis. It is, you know, the primary endpoint analysis at a, at a, you know, in a smaller event rate. You know, there is always possibility that, interim analysis may cross the statistical boundary.

Speaker #1: That kind of data while plausible is there is such paucity of the data. So we can't really establish the relationship other than saying, well, it is plausible that if we see greater MRD clearance difference, that may treat translate to greater clinical benefit.

Speaker #1: And I get to the point about how that may sort of put us in the time of interim EF analysis. I mean, interim EF analysis is of us spending analysis.

David Chang: I mean, interim EFS analysis is alpha spending analysis. It is, you know, the primary endpoint analysis at a, at a, you know, in a smaller event rate. You know, there is always possibility that, interim analysis may cross the statistical boundary.

Speaker #1: It is the primary endpoint analysis at a smaller event rate. And there is always the possibility that interim analysis may cause the statistical boundary. I mean, that's part of the reason that we do the interim analysis—not just us, everybody who does the interim analysis—but let's stay tuned.

David Chang: I mean, that's why part of the reason that we do the interim analysis, not just us, everybody who does the interim analysis. Let's stay tuned. I mean, our focus right now is the, you know, the MRD clearance, you know, that we promised to communicate in April of this year. With the second question on the target product profile with the autoimmune program, our CD19/CD70, as Zach has covered in his prepared statement, this is highly differentiated program that is endowed with a Dagger technology that may enable ALLO-329 to work at low or no lymphodepletion. In the ongoing study, the baseline case that we are testing is low lymphodepletion, which is essentially using cyclophosphamide only. Standard lymphodepletion involves both cyclophosphamide and fludarabine.

Speaker #1: I mean, our focus right now is the MRD clearance that we promised to communicate in April of this year. And with the second question on the target product profile with the autoimmune program, our CD19, CD70, as Zach has covered in his prepared statement, this is highly differentiated program.

Speaker #1: That is endowed with a dagger technology that may enable our 329 to work at low or no lymphodepletion. So in the ongoing study, low the baseline case that we are testing is low lymphodepletion.

David Chang: In the ongoing study, the baseline case that we are testing is low lymphodepletion, which is essentially using cyclophosphamide only. Standard lymphodepletion involves both cyclophosphamide and fludarabine.

Speaker #1: Which is essentially using cyclophosphamide only. So standard lymphodepletion involves both cyclophosphamide and fludarabin. We took out the fludarabin altogether and we lowered the cyclophosphamide dose to only one day infusion.

David Chang: You know, we took out the fludarabine altogether, and we lowered the cyclophosphamide dose to only 1 day infusion. That is the baseline case that we are testing. Also we are testing as part of the study, no lymphodepletion. You know, target product profile, you know, we are trying to get to is, you know, providing a meaningful B-cell depletion that's leading to reset of the immune system at cyclophosphamide alone. I think that will be the base case. Obviously, if we can get to that without any lymphodepletion, that will be a great win, not just for the field, but the patients and, you know, everything that people are trying to do with B-cell depletion in the autoimmune space.

Speaker #1: So that is the baseline case that we are testing. And also, we are testing as part of the study no lymphodepletion. So target product profile we are trying to get to is providing a meaningful B-cell depletion that's leading to reset of the immune system.

Speaker #1: At cyclophosphamide alone, I think that will be the base case. And obviously, if we can get to that without any lymphodepletion, that will be a great win.

David Chang: Obviously, if we can get to that without any lymphodepletion, that will be a great win, not just for the field, but the patients and, you know, everything that people are trying to do with B-cell depletion in the autoimmune space.

Speaker #1: Not just for the field, but the patients, and everything that people are trying to do with B-cell depletion in the autoimmune space.

Speaker #2: Thank you. One moment for our next question. Our next question comes from Salvine Richter with Goldman Sachs. Your line is open.

Operator 1: Thank you. One moment for our next question. Our next question comes from Salveen Richter with Goldman Sachs. Your line is open.

Operator: Thank you. One moment for our next question. Our next question comes from Salveen Richter with Goldman Sachs. Your line is open.

Salveen Richter: Good afternoon. Thanks for taking my question. On the overall cema-cel market opportunity and commercial positioning, as CD3 bispecifics move to the front line, this could influence MRD positivity rates or directly exclude patients from cema-cel eligibility. Just curious to get your thoughts on the evolving LBCL landscape and how you see cema-cel positioned long term. Thank you.

Speaker #4: Good afternoon. Thanks for taking my question. On the overall stem of cell market opportunity and commercial positioning, is CD3 bispecifics moved to the front line?

Speaker #4: This could influence MRD positivity rates or directly exclude patients from stem cell eligibility. Just curious to get your thoughts on the evolving LDCL landscape and how you see stem cell positions long term.

Speaker #4: Thank you.

Zachary Roberts: Hey, Salveen, this is Zach. Great question. It's been an interesting few years as these bispecifics have been approved in late lines and now are moving into front line. I think if the early phase 1 data in untreated patients is consistent with the overall phase 3 readouts, there is a likely outcome that a certain percentage of patients may be cured with these very intense upfront regimens. There is a possibility that there will be fewer MRD positive patients. However, I think we very much need to wait for those final data before we begin to consider how the market opportunity may evolve, and not just efficacy, but also safety, and the pace at which these complex and expensive regimens are taken up in the community.

Speaker #5: Hey, Salvine. This is Zach. Great question. So it's been an interesting few years as these bispecifics have been approved in late lines and now we're moving into front line.

Speaker #5: I think if the early phase one data in untreated patients is consistent with the overall phase three readouts, there is a likely outcome that a certain percentage of patients may be cured with these very intense upfront regimens.

Speaker #5: So there is a possibility that there will be fewer MRD positive patients. However, I think we very much need to wait for those final data before we begin to consider how the market opportunity may evolve.

Zachary Roberts: However, I think we very much need to wait for those final data before we begin to consider how the market opportunity may evolve, and not just efficacy, but also safety, and the pace at which these complex and expensive regimens are taken up in the community.

Speaker #5: And not just efficacy, but also safety and the pace at which these complex and expensive regimens are taken up in the community. Our initial feedback is that not everybody is going to be lining up to be giving these very, very complex regimens that often require hospitalization for step-up dosing and so forth.

Zachary Roberts: Our initial feedback is that not everybody is going to be lining up to be giving these very complex regimens that often require hospitalization for step-up dosing and so forth. We're watching this space very carefully, but we believe that the MRD positivity rate is largely gonna be unchanged for the next many years.

Speaker #5: So we're watching this space very carefully, but we believe that the MRD positivity rate is largely going to be unchanged for the next many years.

Operator 1: Thank you. One moment for our next question. Our next question comes from Matt Phipps with William Blair. Your line is open.

Operator: Thank you. One moment for our next question. Our next question comes from Matt Phipps with William Blair. Your line is open.

Speaker #2: Thank you. One moment for our next question. Our next question comes from Matt Phipps with William Blair. Your line is open.

Matt Phipps: Good afternoon, and thanks for taking my questions, and the update on timeline staying on track. When you look at that Foresight CLARITY data that looks at, you know, rates of MRD positivity post R-CHOP, are there any patterns around high risk baseline characteristics such as double hit, triple hit genetics, or, you know, IPI in the fours or something that, you know, you see in those patients that don't reach MRD clearance? Maybe you can remind us how cema-cel performed in those types of subgroups in your previous relapsed/refractory trial. Thank you.

Speaker #6: Good afternoon. Thanks for taking my questions and for the update on the timeline staying on track. When you look at that FORESIGHT CLARITY data that looks at rates of MRD positivity post-R-CHOP, are there any patterns around high-risk baseline characteristics, such as double-hit, triple-hit genetics, or IPI scores in the fours or something that you see in those patients that don't reach MRD clearance?

Speaker #6: And maybe you can remind us how stem of cell performed in those types of subgroups in your previous relapse refractory trial. Thank you.

Zachary Roberts: Great question. This is Zach again. Absolutely, there does appear to be differential MRD positivity rates according to the baseline risk of patients, which is of course no surprise. The MRD positivity at the end of treatment is an extremely high risk for disease progression, and it is precisely disease progression that was used to generate those risk stratification tools. It's very consistent that if you've got a high-risk disease at the time of diagnosis, you are more likely to be MRD positive at the end of frontline treatment and of course then you're more likely to experience a relapse. The beauty of ALPHA3, however, though, is that there are lots of examples out there where patients who even have low-risk disease turn out to be MRD positive at the end of treatment.

Speaker #5: Great question. This is Zach again. So absolutely, there does appear to be differential MRD positivity rates according to the baseline risk of patients, which is, of course, no surprise.

Speaker #5: The MRD positivity at the end of treatment is an extremely high risk for disease progression and it is precisely disease progression that was used to generate those risk stratification tools.

Zachary Roberts: It's very consistent that if you've got a high-risk disease at the time of diagnosis, you are more likely to be MRD positive at the end of frontline treatment and of course then you're more likely to experience a relapse. The beauty of ALPHA3, however, though, is that there are lots of examples out there where patients who even have low-risk disease turn out to be MRD positive at the end of treatment.

Speaker #5: So, it's very consistent that if you've got a high-risk disease at the time of diagnosis, you are more likely to be MRD positive at the end of front-line treatment.

Speaker #5: And of course, then you're more likely to experience a relapse. So the beauty of alpha-3, however, is that there are lots of examples out there where patients who even have low-risk disease turn out to be MRD positive at the end of treatment.

Zachary Roberts: These are the patients that oncologists it keeps oncologists up at night because you think that the patients are gonna do very well, and then they end up experiencing a relapse. One of the things that we find so exciting about ALPHA3 is that everybody gets a shot at upfront cure, and we do the risk stratification at the end of treatment, and then escalate care accordingly with a consolidation dose of cema-cel. Looking back at our phase 1 experience, we definitely saw good activity across the risk spectrum. We do not anticipate there being gross disparities in the risk profile of these patients in the context of ALPHA3.

Speaker #5: And these are the patients that oncologists sort of keep oncologists up at night because you think that the patients are going to do very well and then they end up experiencing a relapse.

Speaker #5: So one of the things that we find so exciting about alpha-3 is that everybody gets a shot at upfront cure, and we do the risk stratification at the end of treatment.

Speaker #5: And then escalate care accordingly with a consolidation dose of stem of cell. Looking back at our phase one experience, we definitely saw good activity across the risk spectrum.

Zachary Roberts: Looking back at our phase 1 experience, we definitely saw good activity across the risk spectrum. We do not anticipate there being gross disparities in the risk profile of these patients in the context of ALPHA3.

Speaker #5: So we do not anticipate there being gross disparities in the risk profile of these patients in the context of alpha-3.

Operator 1: Thank you. One moment for our next question. Our next question comes from Samantha Semenkow with Citi. Your line is open.

Operator: Thank you. One moment for our next question. Our next question comes from Samantha Semenkow with Citi. Your line is open.

Speaker #2: Thank you. One moment for our next question. Our next question comes from Samantha Semiko with City. Your line is open.

[Analyst] (Citi): Hi, this is Ben on for Sam. Sam, thanks so much for taking our question. Can you talk about expectations for the observation arm in the ALPHA3 study? What is the expected rate of spontaneous MRD conversion? If there's any data you could help us to triangulate this? Thank you.

Ben Paluch: Hi, this is Ben on for Sam. Sam, thanks so much for taking our question. Can you talk about expectations for the observation arm in the ALPHA3 study? What is the expected rate of spontaneous MRD conversion? If there's any data you could help us to triangulate this? Thank you.

Speaker #7: Hi. This is Ben on Sam. Thanks so much for taking our question. Can you talk about expectations for the observation arm in the alpha-3 study?

Speaker #7: What is the expected rate of spontaneous MRD conversion? And if there's any data, you could help us triangulate this. Thank you.

Zachary Roberts: Hey, Ben, this is Zach again. Great question. We get asked this one quite a lot. We have long assumed that the number of patients who are clearing MRD without further treatment will be a non-zero number. We've modeled at about 20%. In the 12-patient arm that we'll be revealing next month, we're talking about 2 to 3 patients that we expect to potentially have an MRD conversion from positive to negative. This comes back to the fact that no test in medicine is perfect. There are false positives and false negatives with every single test that you can perform, including PET scan.

Speaker #5: Hey, Ben. This is Zach again. Great question. We get asked this one quite a lot. So we have long assumed that the number of patients who are clearing MRD without further treatment will be a non-zero number.

Speaker #5: We've modeled it at about 20%. So, in the 12-patient arm that we'll be revealing next month, we're talking about 2 to 3 patients that we expect to potentially have an MRD conversion from positive to negative.

Speaker #5: This comes back to the fact that no test in medicine is perfect. There are false positives and false negatives with every single test that you can perform, including PET scan.

Zachary Roberts: In fact, one of the reasons that MRD is so exciting and we believe will transform the care of these patients is because the false positive and false negative rates of the MRD test are significantly better than they are for PET scan. This is why we are, you know, when we're talking about the efficacy that we hope to see in April next month is relative to the spontaneous clearance rate. When we talk about 25% to 30%, we expect that improvement over the baseline clearance rate because patients, of course, are eligible to spontaneously clear in both arms. We should expect that 20%, distributed in both arms.

Speaker #5: In fact, one of the reasons that MRD is so exciting and we believe will transform the care of these patients is because the false positive and false negative rates of the MRD test are significantly better than they are for PET scan.

Speaker #5: So this is why, when we're talking about the efficacy that we hope to see in April next month, it is relative to the spontaneous clearance rate.

Speaker #5: So when we talk about 25 to 30 percent, we expect that improvement over the baseline clearance rate because patients, of course, are eligible to spontaneously clear in both arms.

Speaker #5: So we should expect that 20% is distributed in both arms. As far as the data that we've used to model this goes, if you look at the publications around the test, the Foresight test, there is a group of about 20 patients—or 20% of patients or so—who are MRD-positive at the end of front-line treatment who never go on to experience disease progression.

Zachary Roberts: As far as the data that we've used to model this goes, if you look at the publications around the test, the Foresight test, there is a group of about 20 patients, 20% of patients or so, who are MRD positive at the end of frontline treatment who never go on to experience disease progression. We've used that number to model the spontaneous clearance rate.

Speaker #5: So we've used that number to model the spontaneous clearance rate.

Operator 1: Thank you. One moment for our next question. Our next question comes from Matthew Biegler with Oppenheimer & Co. Your line is open.

Operator: Thank you. One moment for our next question. Our next question comes from Matthew Biegler with OpCo. Your line is open.

Speaker #2: Thank you. One moment for our next question. Our next question comes from Matthew Biegler with Oppenheimer. Your line is open.

Matthew Biegler: Hey, guys. Wondering how you're thinking about label expansions here, or if you'll need one to include other MRD assays. I know Adaptive has a test out there that's similar. If so, what kind of validation work would that entail? Thanks.

Speaker #8: Hey, guys. Wondering how you're thinking about label expansions here or if you'll need one to include other MRD assays. I know adaptive has a test out there that's similar.

Speaker #8: And if so, kind of what kind of value validation work would that entail? Thanks.

Zachary Roberts: Matt, Zach again here. It's a really good question. Actually, it's a very germane one because you're absolutely right. Adaptive has a test that's been on the market now for a few years. They're seeing rapid uptake across both academic and community centers. We see this as strongly validating that MRD as a concept is gonna become part of the standard of care. They're not the only ones. Of course, Natera, who recently acquired Foresight, also has a test called Signatera that is used for lymphoma. Coming to your question, do we think that we will be restricted to use with Foresight? I think time will tell.

Speaker #5: Matt, Zach again here. So it's a really, really good question. And it's actually a very germane one because you're absolutely right. Adaptive has a test that's been on the market now for a few years.

Speaker #5: They're seeing rapid uptake across both academic and community centers. So we see this as strongly validating that MRD is a concept that's going to become part of the standard of care.

Speaker #5: But they're not the only ones. Of course, Natera who recently acquired Foresight also has a test called Signatera that is used for lymphoma. So coming to your question, do we think that we will be restricted to use with Foresight?

Zachary Roberts: I will say that in other areas of oncology where a diagnostic test has been required to determine eligibility for treatment, very rapidly, there is a proliferation of people using different tests to determine eligibility for targeted therapy, for example, without necessarily requiring a specific regulatory approval. We are, of course, watching this very carefully, but, you know, we believe that there will be some ability to mix and match in a commercial context.

Speaker #5: I think time will tell. I will say that in other areas of oncology where a diagnostic test has been required to determine eligibility for treatment, very rapidly there is a proliferation of people using different tests to determine eligibility for targeted therapy, for example, without necessarily requiring a specific regulatory approval.

Speaker #5: So we are, of course, watching this very carefully. But we believe that there will be some ability to mix and match in a commercial context.

Operator 1: Thank you. One moment for our next question. Our next question comes from Asthika Gunawardene with Truist. Your line is open.

Operator: Thank you. One moment for our next question. Our next question comes from Asthika Goonewardene with Truist. Your line is open.

Speaker #2: Thank you. One moment for our next question. Our next question comes from Ashleika Gunawaradeen with Truist. Your line is open.

Speaker 19: Hey, guys. Thanks for taking my question, and thanks for all the updates too. Just a quick one from me. What proportion of the community centers that were treating patients on the ALPHA3 study had previously had auto CAR T, and/or transplant capabilities? I'm just trying to tease out, like, you know, as you roll this out into trial sites in the community, where if you had a substantial number of centers that is their first of going to the CAR T rodeo with an Allogene product.

Asthika Goonewardene: Hey, guys. Thanks for taking my question, and thanks for all the updates too. Just a quick one from me. What proportion of the community centers that were treating patients on the ALPHA3 study had previously had auto CAR T, and/or transplant capabilities? I'm just trying to tease out, like, you know, as you roll this out into trial sites in the community, where if you had a substantial number of centers that is their first of going to the CAR T rodeo with an Allogene product.

Speaker #4: Hey, guys. Thanks for taking my question. And thanks for all the updates too. Just a quick one from me. What proportion of the community centers that we're treating patients on the alpha-3 study had previously had autocar-T and/or transplant capabilities?

Speaker #4: Just sort of tease out, as you roll this out into trial sites in the community, where, if you had a substantial number of centers, that is the first point in the CAR-T rodeo with an allogeneic product?

Zachary Roberts: Hi, Asthika. Zach again. If I wanna make sure I understand the question. Are you asking how many patients in the ALPHA3 study have previously been treated with transplants or auto CAR?

Speaker #5: I asked Zach again. So if I want to make sure I understand the question, are you asking how many patients in the alpha-3 study have previously been treated with transplant or autocar?

Speaker 19: Which sites have had?

Asthika Goonewardene: Which sites have had?

Zachary Roberts: I see.

Speaker 19: No, no. Yeah, yeah.

Zachary Roberts: There-

Speaker 19: Looking specifically at the sites. I'm just wondering about, you know, site activation and how, if they didn't have any allo CAR T capabilities or transplant capabilities, if you were able to successfully bring them on board and

Speaker #4: Sites have had—no, no. Yeah, yeah. We're looking specifically at the sites. I'm just wondering about site adaptation and how, if they didn't have any auto-CAR-T capabilities or transplant capabilities, if you were able to successfully bring them on board and have them set up for allo-CAR-T.

Zachary Roberts: Yes.

Speaker 19: have them set up the allo CAR T.

Zachary Roberts: Got it. Yes. Okay, great question. The study is open in about 60 sites now in North America. We've said it's roughly 50/50 community and academic. Of the community practices, a subset of those are CAR T naive, so to speak. They've never given CAR T. They don't have a transplant program. Those centers are actively enrolling and treating patients in ALPHA3 using cema-cel as their very first CAR T that they've ever given to their patient. I can say that it has gone very smoothly at those centers, and we are seeing very good uptake, very good tolerability with the product.

Speaker #5: Got it. Yes. Okay. Great question. So the study is open in about 60 sites now in North America. We've said it's roughly 50/50 community and academic.

Speaker #5: Of the community practices, a subset of those are CAR-T naive, so to speak. They've never given CAR-T. They don't have a transplant program. And those centers are actively enrolling and treating patients in alpha-3 using semicell as their very first CAR-T that they've ever given to their patient.

Speaker #5: And I can say that it has gone very smoothly at those centers. And we are seeing very good uptake, very good tolerability with the product.

Zachary Roberts: Because this is, you know, can be done right at the bedside, administered in an infusion clinic, there isn't the need for the infrastructure or the dedicated team to manage autologous CAR T transplant. We've been able to kind of slot right into how these clinics run their day-to-day infusions.

Speaker #5: And because this can be done at the bedside or administered in an infusion clinic, there isn't the need for the infrastructure or the dedicated team to manage autologous CAR-T or transplant.

Speaker #5: So we've been able to kind of slot right into how these clinics run their day-to-day infusions.

Speaker 20: Thanks, Zach. I'm just wondering, are you able to comment on maybe what proportion of the community setting, community centers are these allo CAR T naive sites?

Speaker #4: Thanks, Zach. I'm just wondering, are you able to comment on maybe what proportion of the community-setting community centers are these autocar-T naive sites?

Zachary Roberts: I would say that I'm not gonna be able to do that off the top of my head here. The sites that are listed on our ClinicalTrials.gov will, you know, they're all listed out there by sites. We'll provide a little bit more information on this at the time of the data update in next month.

Speaker #5: So I would say that I'm not going to be able to do that off the top of my head here. The sites that are listed on our clinicaltrials.gov—they're all listed out there by sites.

Speaker #5: We'll provide a little bit more information on this at the time of the data update next month.

Speaker 20: Great. Looking forward to it. Thanks, guys.

Operator 1: Thank you. One moment for our next question. Our next question comes from John Newman with Canaccord Genuity. Your line is open.

Operator: Thank you. One moment for our next question. Our next question comes from John Newman with Canaccord Genuity. Your line is open.

Speaker #4: Great. Looking forward to it. Thanks, guys.

Speaker #2: Thank you. One moment for our next question. Our next question comes from John Newman with Canaccord Genuity. Your line is open.

Speaker 21: Hi, guys. Thanks for taking my question. Just had a question on ALLO-329 in the RESOLUTION trial. Just curious when you present top line data, if you plan to present any data on not just depletion of CD19 positive B cells, but depletion of the CD70 positive T cells, and also curious as to, you know, roughly what type of a time point, after treatment, you're looking at presenting data. Thanks.

Speaker #6: Hi, guys. Thanks for taking my question. Just had a question on L329 in the resolution one trial. Just curious when you present top-line data, if you plan to present any data on not just depletion of CD19 positive B cells, but depletion of the CD70 positive T cells, and also curious as to roughly what type of a time point after treatment you're looking at presenting data.

David Chang: Hey, John, let me give Zach a break and respond to your question. In ALLO-329, the RESOLUTION study in autoimmunes, you know, indication, you know, that study is progressing well. It is a dose escalation study, and as Zach had covered in the prepared remarks, we are starting at very conservative dose of 20 million cells just to safeguard the patients with a product that has never been tested in humans. The study's ongoing, and at the time of the data analysis, many of the things and more, a lot of translational data, you know, we have plans. We are collecting the samples, and we have plans to analyze. You know, probably at this point it's too premature to go into details of time points of, you know, sample collection, you know.

Speaker #6: Thanks.

Speaker #4: Hey, John. Let me give Zach a break and respond to your question. So, L329—the resolution study in the autoimmune indication—that study is progressing well.

Speaker #4: It is a dose escalation study. And as Zach had covered in the prepared remarks, we are studying at a very conservative dose of 20 million cells just to safeguard the patients.

Speaker #4: With a product that has never been tested in humans, the study is ongoing. At the time of the data analysis, many of the things—and more, a lot of translational data—we have plans. We are collecting the samples, and we have plans to analyze.

Speaker #4: Probably at this point, it is too premature to go into details of time points of sample collection. But the data communication, which will be primarily focused on those level one, I mean, we believe that's about the time that we may come to treat all the dose level one patients.

David Chang: The data communication, which will be primarily focused on dose level one, I mean, we believe that's about the time that, you know, we may come to, you know, treat all the dose level one patients. You know, the translational aspect of what we are seeing with the 20 million dose will be the focus of the data communication.

Speaker #4: And translational aspect of what we are seeing with the 20 million dose will be the focus of the data communication.

Speaker 21: Okay, great. Thank you.

Operator 1: One moment for our next question. Our next question comes from Jack Allen with Baird. Your line is open.

Operator: One moment for our next question. Our next question comes from Jack Allen with Baird. Your line is open.

Speaker #6: Okay. Great. Thank you.

Speaker #2: One moment for our next question. Our next question comes from Jack Allen with Baird. Your line is open.

Speaker 22: Hi, everyone. Thanks for taking my question. This is Chris on for Jack Allen. Just going back to ALPHA3, I was just curious if you can provide some more color on just the overall pace of enrollment for the study. Just a follow-up to that, I know you're limited on how much you can share, on an ongoing trial, but can you share whether the percentage of patients showing MRD positivity following R-CHOP is similar, to your expectations heading into it? Thank you.

Speaker #7: Hi, everyone. Thanks for taking my question. This is Chris on for Jack. Just going back to alpha-3, I was just curious if you can provide some more color on the overall pace of enrollment for the study, and then just a follow-up to that.

Speaker #7: I know you're limited on how much you can share on an ongoing trial. But can you share whether the percentage of patients showing MRD positivity following R-CHOP is similar to your expectations heading into it?

Zachary Roberts: Hey, Chris. Zach again. You know, we don't give kind of month-to-month updates on the pace of enrollment. We have said that we expect to complete enrollment in the trial by the end of 2027, so that is very much on track. With respect to your second question, is the rate of MRD positivity consistent with our assumptions? The answer is yes.

Speaker #7: Thank you.

Speaker #5: Hey, Chris. Zach again. So, we don't give kind of month-to-month updates on the pace of enrollment. We have said that we expect to complete enrollment in the trial by the end of 2027.

Speaker #5: So, that is very much on track. And with respect to your second question—'Is the rate of MRD positivity consistent with our assumptions?'—the answer is yes.

Operator 1: Thank you. One moment for our next question.

Operator: Thank you. One moment for our next question.

Speaker #2: Thank you. One moment for our next question. Our next question comes from Brian Cheng with JPMorgan. Your line is open.

Zachary Roberts: Thank you.

Operator 1: Our next question comes from Brian Cheng with JP Morgan. Your line is open.

Operator: Our next question comes from Brian Cheng with JP Morgan. Your line is open.

Speaker 20: Hey, guys. Thanks for taking our questions this afternoon. Just first, can you talk about a little bit about the expectations for the top line? Will there be data to understand the trend of MRD clearance at several time points, or will we only get one MRD rate at one defined time point? If that is the case, can you remind me what time point would that be?

Speaker #8: Hi, guys. Thanks for picking our question this afternoon. Just first, can you talk a little bit about the expectations for the top line?

Speaker #8: Will there be data to understand the trend of MRD clearance at several time points, or will we only get one MRD rate at one defined time point?

Speaker #8: And if that is the case, can you remind me what time point that would be?

Zachary Roberts: Hey, Brian. Zach here. As we've been saying for a few months now, we've kind of outlined how frequently we're monitoring these patients for MRD. We start checking at 45 days post-randomization, then again at 90 days, and then every three months thereafter. As far as the data that we will share next month, we will not be giving kind of longitudinal MRD status patient by patient. We will be giving really top line information, how many patients cleared in the observation arm, how many patients cleared in the treatment arm.

Speaker #5: Hey, Brian. Zach here. So, as we've been saying for a few months now, we've kind of outlined how frequently we're monitoring these patients for MRD.

Speaker #5: So, we start checking at 45 days post-randomization, then again at 90 days, and then every three months thereafter. As far as the data that we will share next month, we will not be giving kind of longitudinal MRD status patient by patient.

Speaker #5: So, we will be giving really top-line information: how many patients cleared in the observation arm, and how many patients cleared in the treatment arm.

Speaker 20: Okay. Just a follow-up. Can you talk about the variability then of MRD clearance that you expect across you know a longitudinal period when you look at this interim first cut of 24 patients?

Speaker #8: Okay. And then just a follow-up—can you talk about the variability, then, of MRD clearance that you expect across a longitudinal period when you look at this interim first cut of 24 patients?

Zachary Roberts: Do you mean, how many patients may fluctuate around? Is that what you mean?

Speaker #5: Do you mean how many patients may fluctuate around? Is that what you mean?

Speaker 20: Yes. Yeah, just the variability based on the different time points. Let's say if you take a look at the MRD rate at 25 days post-randomization, versus let's say, six months down the line. Do you expect some spontaneous, you know, positive to negative or vice versa, between those time periods? How do you think about the variability across these 24 patients?

Speaker #8: Yes. Yeah. Just the variability based on the different time points. So let's say if you take a look at the MRD rate at 25 days post-randomization, versus let's say six months down the line, do you expect some spontaneous positive to negative or vice versa between those time periods?

Zachary Roberts: Got it. Okay. The first thing that you need to keep in mind is that when patients have relapse with large B-cell lymphoma, it tends to happen pretty fast. The median time to disease progression from last dose of treatment is six months or less. MRD is highly predictive of relapse, highly prognostic test, very accurate. We do not expect patients to spend a whole lot of time with very little MRD or MRD positive month after month after month. That's just generally not what happens in the majority of patients. Of course, coming back to a previous question, this idea of false positivity, there are going to be a few patients who have this low level of MRD positivity that never spontaneously clears and who can go for a long time before they relapse.

Speaker #8: How do you think about the variability across these 24 patients?

Speaker #5: Got it. Okay. So the first thing that you need to keep in mind is that when patients have relapse with large B-cell lymphoma, it tends to happen pretty fast.

Speaker #5: The median time to disease progression from the last dose of treatment is six months or less. And so, MRD is highly predictive of relapse, a highly prognostic test, and very accurate.

Speaker #5: So, we do not expect patients to spend a whole lot of time with very little MRD, or MRD positive, month after month after month.

Speaker #5: That's just generally not what happens in the majority of patients. Of course, coming back to a previous question, this idea of false positivity—there are going to be a few patients who have this low level of MRD positivity that never spontaneously clears.

Zachary Roberts: I think we're gonna get a bit of a mixed bag, but for the most part, these patients have very, very high-risk disease, and we expect them to be MRD positive and likely to have disease progression relatively quickly after their last dose of treatment.

Speaker #5: And who can go for a long time before they relapse. So I think we're going to get a bit of a mixed bag. But for the most part, these patients have very, very high-risk disease.

Speaker #5: And we expect them to be MRD positive and likely to have disease progression relatively quickly after their last dose of treatment.

David Chang: Brian, let me just, you know, sort of comment, you know, additional comment. You know, our guidance on what would be a meaningful MRD clearance differential, you know, 25 to 30 percent, you know, also factors in, you know, if there was some kind of, you know, variability due to assay sample collection. As I've said in the prepared remarks, we believe that, you know, the guidance that we have provided, 25 to 30, is very conservative and factors in, you know, many different elements in situations like this. You know, frankly, to Buren's question, the recent publication that again highlights a small difference in MRD clearance can translate to very meaningful difference in the clinical outcome.

Speaker #9: And Brian, let me just sort of comment—additional comment. Our guidance on what would be a meaningful MRD clearance differential—25 to 30 percent—also factors in if there was some kind of variability due to assay sample collection.

Speaker #9: So as I've said in the prepared remarks, we believe that the guidance that we have provided, 25 to 30, is very conservative. And factors in many different elements in situations like this.

Speaker #9: And frankly, to Barron's question, the reason the publication that, again, highlights a small difference in MRD clearance can translate to a very meaningful difference in the clinical outcome—I think that is very reassuring to us.

David Chang: You know, I think that is very reassuring to us, and really validates the, you know, one of the key assumptions that went into providing that 25 to 30% guidance.

Speaker #9: And really validates one of the key assumptions that went into providing that 25% to 30% guidance.

Speaker 20: Great. Thank you. Thanks.

Speaker 23: One moment for our next question. Our next question comes from Luca Issi with RBC. Your line is open.

Speaker #8: Great. Thank you. Thanks.

Speaker #2: One moment for our next question. Our next question comes from Luca. I see with RBC, your line is open.

Speaker 24: Hey, team. Thanks so much for taking our question. This is Cassian for Luca, and congrats on all the progress and looking forward to data soon. We have a question on the statistical assumptions for cema-cel. Can you talk about for the futility analysis in a scenario where the delta versus observation is 10% to 15% versus the 20% to 25% that you're hoping to see, which is closer to IMvigor011 versus ZUMA-7, would that prompt you to stop the trial? Again, appreciate you're keeping some of these details close to your vest, but any color on that is much appreciated. Maybe related to it, I think the trial is 220 patients, but you are looking at futility with just 24 patients.

Speaker #10: Hey, team. Thanks so much for taking our questions. This is Cassiano for Luca. And congrats on all the progress. I'm looking forward to data soon.

Speaker #10: We have a question on a statistical assumptions for tumor cell. Can you talk about for the fatality analysis in a scenario where the delta versus observation is 10 to 15 percent versus the 20 to 25 percent that you're hoping to see, which is closer to in vigor 011 versus humor 7?

Speaker #10: Would that prompt you to stop the trial? Again, I appreciate your keeping some of these details close to your vest. But any comment on that is much appreciated.

Speaker #10: And maybe related to it, I think the trial is 220 patients. But you're looking at fertility with just 24 patients. So what gives you the confidence that 24 patients is a large enough sample size?

Speaker 24: What gives you the confidence that 24 patients is a large enough sample size? Thank you, team.

David Chang: Yes. There are many layers of question. Let me give Zach a break. This is David Chang. In terms of, you know, the efficacy aspect, I mean, you know, usually efficacy analysis gets done early on to see, you know, whether, you know, null hypothesis, you know, is in question, in which case, you know, study may be stopped for the lack of efficacy. I think we are a little bit past that point because, earlier last year, you know, because of unrelated event, we had to do a unplanned analysis of MRD clearance with a very few patients. You know, from that data, which we have communicated, where a majority of patients were converting into MRD negativity, we, you know, essentially have cleared the efficacy bar.

Speaker #10: Thank you, team.

Speaker #9: Yeah, so there are many layers of questions. Let me give Zach a break. This is Dave Chang. In terms of the fertility aspect, I mean, usually fertility analysis gets done early on to see whether another hypothesis is in question, in which case the study may be stopped for lack of fertility.

Speaker #9: I think we are a little bit past that point, because earlier last year, because of an unrelated event, we had to do an unplanned analysis of MRD clearance with very few patients.

Speaker #9: And from that data, which we have communicated, where a majority of patients were converting into MRD negativity, we essentially have cleared the fertility bar.

David Chang: You know, we have made some remarks about, you know, in some ways, this interim futility analysis, a misnomer, because it's really, you know, trying to get an early signs of what's going on with MRD clearance. That will be, you know, communicated. With respect to the statistical, you know, aspect of, the study, you know, powering and all that, you know, those are the details that, we haven't shared. You know, frankly, you know, those are information that's better suited, for when the study is complete and published, providing all the details. We will, you know, continue to be a little bit coy about not providing any statistical powering of assumptions behind the study.

Speaker #9: So, we have made some remarks about, in some ways, this interim fertility analysis is a misnomer, because it's really trying to get early signs of what's going on with the MRD clearance.

Speaker #9: So, that will be communicated. With respect to the statistical aspect of the study—powering and all that—those are the details that we haven't shared.

Speaker #9: And frankly, those are information that's better suited for when the study is complete and published, providing all the details. So we will continue to be a little bit coy about not providing any statistical powering and assumptions behind the study.

David Chang: With respect to what the control arm versus the treatment arm we may see, you know, when we say 25% to 30% is absolute delta we're talking about. If the control arm has baseline MRD clearance or MRD positive patient going to MRD negativity for any reason, at, you know, 15% to 20%, what we expect to see is in the treatment arm, that's 25% to 30%, in addition to that, 45% to 50%. That's more or less what we have been sort of setting the bar for the futility analysis.

Speaker #9: But with respect to what the control arm versus the treatment arm, we may see—when we say 25 to 30 percent is absolute delta, we're talking about that.

Speaker #9: So if the control arm has baseline MRD clearance, or MRD positive patients going to MRD negativity, for any reason, at 15% to 20%, what we expect to see is in the treatment arm, that’s 25% to 30% in addition to that 45% to 50%.

Speaker #9: So that's more or less what we have in, sort of, setting the bar for the fertility analysis.

Michael Yee: Thanks, David.

Operator 2: I'm not showing any further questions at this time. I'd like to turn the call back over to management for any further remarks.

Michael Yee: I'm not showing any further questions at this time. I'd like to turn the call back over to management for any further remarks.

Speaker #10: Thanks, David.

David Chang: Well, thank you very much, and thank you for very sort of poignant and engaging questions. We said at the onset that cell therapy has entered a phase defined by evidence. That is where we intend to compete through data, disciplined execution, and proof. The questions facing the field is no longer theoretical. I would say they are practical questions. Can these therapies be delivered broadly? Can they move earlier in the disease course? Can they extend beyond highly specialized cell therapy centers? And can they do so in a way that is sustainable? At Allogene, those are the questions we have been building towards from the beginning. With cema-cel, we are testing whether intervening at the point of molecular relapse can change the trajectory of disease.

Speaker #2: And I'm not showing any further questions at this time. I'd like to turn the call back over to management for any further remarks.

Speaker #9: Well, thank you very much. And thank you for very, sort of, pertinent and engaging questions. We said at the onset that cell therapy has entered a phase defined by evidence.

Speaker #9: That is where we tend to compete—through data, disciplined execution, and proof. The questions facing the field are no longer theoretical. I would say they are practical questions.

Speaker #9: Can these therapies be delivered broadly? Can they move earlier in the disease course? Can they extend beyond highly specialized cell therapy centers? And can they do so in a way that is sustainable?

Speaker #9: At Allogene, those are the questions we have been building towards from the beginning. With tumor cell, we are testing whether intervening at the point of molecular relapse can change the trajectory of disease.

David Chang: With ALLO-329, we are evaluating whether a purpose-built dual targeted allogeneic CAR T can open a new chapter in autoimmune disease, one defined by scalability and accessibility. The coming year will not be about projections. It will be about proof. With runway into Q1 2028, we are positioned to execute with discipline and let the data guide what comes next. Thank you for your continued support. Operator, you may now disconnect.

Speaker #9: With ALLO-329, we are evaluating whether a purpose-built, dual-targeted allogeneic CAR T can open a new chapter in autoimmune disease—one defined by scalability and accessibility.

Speaker #9: The coming year will not be about projections; it will be about proof. And with runway into the first quarter of 2028, we are positioned to execute with discipline and let the data guide what comes next.

Operator 2: Thank you. Ladies and gentlemen, this concludes today's presentation. You may now disconnect and have a wonderful day.

David Chang: Thank you. Ladies and gentlemen, this concludes today's presentation. You may now disconnect and have a wonderful day.

Speaker #9: Thank you for your continued support. Operator, you may now disconnect.

Q4 2025 Allogene Therapeutics Inc Earnings Call

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