Q2 2025 Allogene Therapeutics Inc Earnings Call
Operator: Hello, and thank you for standing by, and welcome to Alogene Therapeutics' second quarter 2025 conference call. After the speaker's presentation, there will be a question and answer session. To ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. At this time, all participants are in a listen-only mode. 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 #2: Hello, and thank you for standing by. Welcome to Allogene Therapeutics' second quarter 2025 conference call. After the speakers' presentation, there will be a question-and-answer session.
Speaker #2: To ask a question, please press *1 1 on your telephone and wait for your name to be announced. To withdraw your question, please press *1 1 again.
Speaker #2: At this time, all participants are in a listen-only mode. Please be aware that today's conference call is being recorded. I would now like to turn the call over to Christine Cassiano.
Speaker #2: Chief Corporate Affairs and Brand Strategy Officer, Ms. Cassiano, please go ahead.
David Chang: Thank you, Operator, and thank you for joining this call. After the market closed, Alogene issued a press release that provided a business update and financial results for the second quarter of 2025. This press release and today's webcast are available on our website. Following our prepared remarks, we will host a Q&A session. We recognize that historically, questions have been multifaceted, but note that we will endeavor to keep this call to under an hour. I am 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 #3: Thank you, Operator, and thank you for joining this call. After the market closed, Allogene issued a press release that provided a business update and financial results for the second quarter of 2025.
Speaker #3: This press release and today's webcast are available on our website. Following our prepared remarks, we will host a Q&A session. We recognize that historically, questions have been multifaceted, but note that we will endeavor to keep this call to under an hour.
Speaker #3: I am 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.
Speaker #3: During today's call, we will be making certain forward-looking statements. These may include statements regarding the success and timing of our ongoing and planned clinical trials, data presentations, regulatory filings, future research and development efforts, manufacturing capabilities, the safety and efficacy of our product candidates, commercial market forecasts, and financial guidance, among other things.
David Chang: 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. We are cautioned not to place undue reliance on these forward-looking statements, and Alogene disclaims any obligation to update these statements. I'll now turn the call over to David.
Speaker #3: 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.
Speaker #3: Your caution not to place undue reliance on these forward-looking statements is noted, and Allogene disclaims any obligation to update these statements. I'll now turn the call over to David.
David Chang: Thank you, Christine, and welcome, everyone. This past quarter marked a period of significant advancement across our portfolio, with progress that highlights how scientific excellence, rigorous decision-making, and thoughtful planning and execution can coalesce into transformative momentum. We are seeing the power of this approach across our pipeline, from SemaCell in first-line consolidation for large B-cell lymphoma to LO316 in solid tumors, and now LO329 in autoimmune disease. Let me begin with SemaCell in the Alpha 3 study. The Alpha 3 study has been streamlined into a two-arm randomized trial comparing treatment with SemaCell following a standard lymphodepletion regimen of buldarobine and cyclophosphamides in the active arm to observation in the control arm. This decisive move, made in conjunction with the Data Safety Monitoring Board and Steering Committee, reflects our unwavering commitment to patient safety.
Speaker #2: Thank you, Christine, and welcome, everyone. This past quarter marked a period of significant advancement across our portfolio. With progress that highlights how scientific excellence rigorous decision-making and thoughtful planning and execution can call us into transformative momentum.
Speaker #2: We are seeing the power of this approach across our pipeline. From semicell in the first-line consolidation for large B-cell lymphoma, to Allo316 in cell tumors, and now Allo329 in autoimmune disease.
Speaker #2: Let me begin with semicell in the alpha-3 study. The alpha-3 study has been streamlined into a two-arm randomized trial comparing treatment with semicell following a standard lymphodepletion regimen of fludarabine and cyclophosphamide in the active arm to observation in the control arm.
Speaker #2: This decisive move made in conjunction with the data safety monitoring board and steering committee reflects our unwavering commitment to patient safety. It also reflects our ability to act swiftly balancing scientific judgment with agility to create and preserve the long-term value of our platform.
David Chang: It also reflects our ability to act swiftly, balancing scientific judgment with agility to create and preserve the long-term value of our platform. I also would like to thank the review team at the FDA that provided prompt informal consultation and guidance. More than 50 sites are now activated across the US and Canada, and additional international expansion is underway. We remain on track for the planned fertility analysis in the first half of 2026 and expect to share MRD conversion rates at that time. The changes to the protocol exemplify our vision to redefine CAR T therapy by prioritizing patient accessibility in every stage of development. Turning to LO316, our CD70-targeted CAR T for renal cell carcinoma, we presented compelling Phase 1 data at ASCO 2025.
Speaker #2: I also would like to thank the review team at the FDA that provided prompt informal consultation and guidance. More than 50 sites are now activated across the US and Canada, and additional international expansion is underway.
Speaker #2: We remain on track for the planned fertility analysis in the first half of 2026, and expect to share MRD conversion rates at that time.
Speaker #2: The changes to the protocol exemplify our vision to redefine CAR-T therapy by prioritizing patient accessibility in every stage of development. Turning to Allo316, our CD70 targeted CAR-P4 renal cell carcinoma, we presented compelling phase I data at ASCO 2025.
David Chang: This trial serves as a significant proof point for our Dagger platform and how this technology may define the future of off-the-shelf cell therapy. The results seen to date from the Traverse trial underscore the potential for Dagger technology to support both robust expansion of CAR T cells and durable clinical responses in solid tumors. We have since aligned with the FDA on a pivotal trial strategy and are actively exploring partnership opportunities with several third parties to advance this program. In autoimmune disease, we opened enrollment in the Resolution Study, one of the first allogeneic CAR T trials in this space and the first of such to contemplate a new approach to lymphodepletion. We have designed both our allocated CAR T product and the trial itself with patient accessibility, not as an afterthought but as a priority from the offset.
Speaker #2: This trial serves as a significant proof point for our Dagger platform and how this technology may define the future of off-the-shelf cell therapy. The results seem to date from the traversed trial and underscore the potential for Dagger technology to support both robust expansion of CAR-T cells and durable clinical responses in cell tumors.
Speaker #2: We have since aligned with the FDA on a pivotal trial strategy and are actively exploring partnership opportunities with several third parties to advance this program.
Speaker #2: In autoimmune disease, we often enrollment in the resolution study, one of the first allogeneic CAR-T trials in this space and the first of such to contemplate a new approach to lymphodepletion.
Speaker #2: We have designed both our AlloCAR-T product and the trial itself with patient accessibility not as an afterthought but as a priority from the outset.
David Chang: By simplifying or eliminating lymphodepletion altogether, we are testing both hypotheses grounded in strong science and clinical insight. This study reflects not only our ambition but also our readiness to challenge paradigms with data. Each of these advances is rooted in the belief that the breakthroughs are not born by chance; they are built. They emerge from a foundation of strong science, disciplined execution, cross-functional collaboration, and the agility to adapt and evolve when circumstances change. Nowhere is this more evident than in cell therapy, a field with a potential to transform how we treat disease and, in doing so, generate extraordinary value for those who invest in companies that have demonstrated the ability to navigate the terrain. While early optimism often fuels bold ambition, reality is often far more complex, especially in the unforgiving terrain of clinical development where transformative ideas must be tested and refined.
Speaker #2: By simplifying or eliminating lymphodepletion altogether, we are testing both hypotheses grounded in strong science and clinical insight. This study reflects not only our ambition but also our readiness to challenge paradigms with data.
Speaker #2: Each of these advances is rooted in the belief that the breakthroughs are not born but of chance. They are built. They emerge from foundations of strong science, disciplined execution, cross-functional collaboration, and the agility to adapt and evolve when circumstances change.
Speaker #2: Nowhere is this more evident than in cell therapy, a field with a potential to transform how we treat disease and in doing so generate extraordinary value for those who invest in companies that have demonstrated the ability to navigate the terrain.
Speaker #2: While early optimism often feels bold ambition, reality is often far more complex. Especially in the unforgiving terrain of clinical development, we are transformative idea must be tested and refined.
David Chang: That's why many have started on this path, yet only a few have advanced beyond the early promise. Alogene stands among the few that have successfully persevered in this field. From the beginning, we have committed to these principles, not just in theory but in practice. Today, we are one of the last allogeneic cell therapy companies standing and the one with the most diverse and advanced clinical pipeline, and we take that position seriously. While the finish line in this field is neither fixed nor guaranteed, our continued progress reflects the depth of our platform, the strength of our team, and our unwavering commitment to doing the hard, necessary work that real innovation demands. As we look ahead, our near-term milestones are more than clinical achievements. We believe they are value-driving catalysts that reinforce our foundation and advance our vision of making allogeneic CAR T the standard of care.
Speaker #2: That's why many have started on this path, yet only a few have advanced beyond the early promise. Allogene stands among the few that have successfully persevered in this field.
Speaker #2: From the beginning, we have committed to these principles. Not just in theory, but in practice. Today, we are one of the last allogeneic cell therapy companies standing.
Speaker #2: And the one with the most diverse and advanced clinical pipeline. We take that position seriously. While the finish line in this field is neither fixed nor guaranteed, our continued progress reflects the depth of our platform, the strength of our team, and our unwavering commitment to doing the hard, necessary work that real innovation demands.
Speaker #2: As we look ahead, our near-term milestones are more than clinical achievements. We believe they are value-driving catalysts that reinforce our foundation and advance our vision of making allogeneic CAR-T the standard of care.
David Chang: I want to thank the entire Alogene team for their passion and commitment and give a special thanks to Zach for his steady leadership in R&D. The choices we made this quarter really reflect our responsibility to move boldly and thoughtfully, always keeping patients at the center. With that, I'll hand it over to Zach.
Speaker #2: I want to thank the entire Allogene team for their passion and commitment. And give a special thanks to Zach for his steady leadership in R&D.
Speaker #2: The choices we made this quarter really reflect our responsibility to move boldly and thoughtfully. Always keeping patients at the center. With that, I'll hand it over to Zach.
Zachary Roberts: Thank you, David. I want to start with a personal reflection on Alpha 3 and the journey this trial has taken. The hypothesis that patients whose only evidence of disease was MRD positivity could be cured by SemaCell without the need to use enhanced lymphodepletion was always compelling. Standard FC is widely used, well-tolerated, and critically easier for doctors to give and patients to receive than a regimen that includes an additional infusion of an anti-CD52 monoclonal antibody. Furthermore, because these patients are just coming off six cycles of treatment, they are partially lymphodepleted already. For these reasons, we designed the study to test this hypothesis by comparing standard FC to the enhanced regimen that included allocation 647 or anti-CD52 monoclonal antibody.
Speaker #4: Thank you, David. I want to start with a personal reflection on Alpha-3 and the journey this trial has taken. The hypothesis that patients whose only evidence of disease was MRD positivity could be cured by semi-cell without the need to use enhanced lymphodepletion was always compelling.
Speaker #4: Standard FC is widely used, well tolerated, and critically easier for doctors to give and patients to receive than a regimen that includes an additional infusion of an anti-CD52 monoclonal antibody.
Speaker #4: Furthermore, because these patients are just coming off six cycles of treatment, they are partially lymphodepleted already. For these reasons, we designed the study to test this hypothesis by comparing standard FC to the enhanced regimen that included Allo647 or the anti-CD52 monoclonal antibody.
Zachary Roberts: While the recent developments in the trial required that we make a decision on lymphodepletion sooner than planned to ensure the safety of patients in the trial, the early biomarker and safety data emerging from the standard FC arm has given us confidence that the trial is moving ahead with the right treatment regimen. From the beginning, standard FC is the regimen we always hoped would be the ultimate outcome, potentially optimizing benefit-risk and front-line consolidation and driving greater uptake in both the clinical trial and commercial settings. Following this selection, Alpha 3 is now proceeding as a two-arm randomized trial comparing SemaCell after FC lymphodepletion versus observation. With more than 50 sites now open and incoming interest from new investigators globally, we continue to see a high degree of engagement from our sites and are continuing to add patients to the pipeline for MRD screening to support enrollment.
Speaker #4: While the recent developments in the trial required that we make a decision on lymphodepletion sooner than planned to ensure the safety of patients in the trial, the early biomarker and safety data emerging from the standard FC arm has given us confidence that the trial is moving ahead with the right treatment regimen.
Speaker #4: From the beginning, standard FC is the regimen we'd always hoped would be the ultimate outcome. Potentially optimizing benefit-risk and frontline consolidation and driving greater uptake in both the clinical trial and commercial settings.
Speaker #4: Following this selection, alpha-3 is now proceeding as a two-arm randomized trial comparing Semicell after FC lymphodepletion versus observation. With more than 50 sites now open and incoming interest from new investigators globally, we continue to see a high degree of engagement from our sites and are continuing to add patients to the pipeline for MRD screening to support enrollment.
Zachary Roberts: For many sites, the simplification and streamlining of the study through the removal of the FCA arm is expected to boost participation and further strengthen engagement. In fact, the response of investigators to this design change has been quite positive, reinforcing our confidence that the path forward improves the safety and scalability of the study while significantly enhancing its appeal to participating centers. Accordingly, we remain on track for the planned fertility analysis in the first half of 2026, which will assess MRD conversion rates between the two arms and provide a critical early signal of efficacy. This is the intersection of science, clinical design, and discipline execution, and where meaningful progress is made. Turning to LO316, our Phase 1B data presented at ASCO showed promising responses in a heavily pretreated RCC population. The strength of our Dagger platform supported exceptional CAR T expansion and persistence.
Speaker #4: For many sites, the simplification and streamlining of the study through the removal of the FCA arm is expected to boost participation and further strengthen engagement.
Speaker #4: In fact, the response of investigators to this design change has been quite positive, reinforcing our confidence that the path forward improves the safety and scalability of the study while significantly enhancing its appeal to participating centers.
Speaker #4: Accordingly, we remain on track for the planned fertility analysis in the first half of 2026, which will assess MRD conversion rates between the two arms and provide a critical early signal of efficacy.
Speaker #4: This is the intersection of science, clinical design, and discipline execution, and where meaningful progress is made. Turning to Allo316, our phase IB data presented at ASCO showed promising responses and a heavily pretreated RCC population.
Speaker #4: The strength of our dagger platform supported exceptional CAR-T expansion of persistence. As David noted earlier, following recent alignment with the FDA on a pivotal trial design, we're actively exploring partnership opportunities to advance the program.
Zachary Roberts: As David noted earlier, following recent alignment with the FDA on a pivotal trial design, we're actively exploring partnership opportunities to advance the program. Resolution, our study in autoimmune disease, is now open and actively screening patients. This trial represents a meaningful expansion of our platform into a new disease area and into uncharted territory for the field. It allows us to explore how we might fine-tune the levers of lymphodepletion with greater precision. By reducing or potentially eliminating lymphodepletion, we're taking a bold step toward reshaping what's possible in the treatment of immune-mediated conditions. If successful, Resolution could serve as the foundation for a new therapeutic paradigm; we look forward to providing an update on the early clinical results from the Resolution Study in the first half of 2026. Taken together, these programs reflect both the maturity of our platform and the clarity of our strategy.
Speaker #4: Resolution, our study in autoimmune disease, is now open and actively screening patients. This trial represents a meaningful expansion of our platform into a new disease area and into uncharted territory for the field.
Speaker #4: It allows us to explore how we might fine-tune the levers of lymphodepletion with greater precision. By reducing or potentially eliminating lymphodepletion, we're taking a bold step toward reshaping what's possible and the treatment of immune-mediated conditions.
Speaker #4: If successful, resolution could serve as the foundation for a new therapeutic paradigm. We look forward to providing an update on the early clinical results from the resolution study in the first half of 2026.
Speaker #4: Taken together, these programs reflect both the maturity of our platform and the clarity of our strategy. This is no longer conceptual; it's advanced clinical development moving forward because of the discipline, foresight, and steady execution by our team.
Zachary Roberts: This is no longer conceptual; it's advanced clinical development moving forward because of the discipline, foresight, and steady execution by our team. We've entered a stage where conviction matters. As R&D leaders, we're called to rely on the strength of our science. In cell therapy, we must make complex decisions, but we are confident in the direction we're heading and even more so in the evidence that's pointing us forward. In the coming months, you will see us continue to advance these studies built on the momentum we've created and stay focused on delivering not only clinical value but a durable platform capable of changing how patients are treated across multiple diseases. With that, I'll hand the call over to Geoff.
Speaker #4: We've entered a stage where conviction matters. As R&D leaders, we're called to rely on the strength of our science. In cell therapy, we must make complex decisions, but we are confident in the direction we're heading, and even more so in the evidence that's pointing us forward.
Speaker #4: In the coming months, you will see us continue to advance these studies, build on the momentum we've created, and stay focused on delivering not only clinical value but a durable platform capable of changing how patients are treated across multiple diseases.
Speaker #4: With that, I'll hand the call over to Geoff.
Geoffrey Parker: Thank you, Zach. As David and Zach have outlined, our operational progress has been matched by disciplined financial stewardship. As of June 30, 2025, we had $302.6 million in cash, cash equivalents, and investments. Our cash runway continues to extend into the second half of 2027. R&D expenses for the second quarter were $40.2 million, including $2.6 million of non-cash stock-based compensation. G&A expenses for the second quarter were $14.3 million, including $6.1 million in non-cash stock-based compensation. Net loss for the second quarter was $50.9 million, or $0.23 per share, including non-cash stock-based compensation expense of $8.7 million and non-cash impairment of long-lived asset expenses of $2.4 million. We continue to expect a 2025 cash burn of approximately $150 million and full-year GAAP operating expenses of approximately $230 million, which includes an estimated non-cash stock-based compensation expense of approximately $45 million.
Speaker #5: Thank you, Zach. As David and Zach have outlined, our operational progress has been matched by disciplined financial stewardship. As of June 30, 2025, we had 302.6 million dollars in cash, cash equivalents, and investments.
Speaker #5: Our cash runway continues to extend into the second half of 2027. R&D expenses for the second quarter were 40.2 million dollars, including 2.6 million dollars of non-cash stock-based compensation.
Speaker #5: G&A expenses for the second quarter were 14.3 million dollars, including 6.1 million dollars in non-cash stock-based compensation. Net loss for the second quarter was 50.9 million dollars, or 23 cents per share, including non-cash stock-based compensation expense, of 8.7 million dollars, and non-cash impairment of long-lived asset expenses of 2.4 million dollars.
Speaker #5: We continue to expect 2025 cash burn of approximately $150 million, and full-year GAAP operating expenses of approximately $230 million, which includes an estimated non-cash stock-based compensation expense of approximately $45 million.
Geoffrey Parker: This guidance excludes any impact from potential business development activities. Let me conclude by highlighting that our allogeneic platform allows us to manufacture product well in advance and at scale, supporting trial execution while enabling cost reductions. With a refined strategy and strong clinical catalysts ahead, we remain confident in our position. We'll now open the call for questions.
Speaker #5: This guidance excludes any impact from potential business development activities. Let me conclude by highlighting that our allogeneic platform allows us to manufacture products well in advance and at scale, supporting trial execution while enabling cost reductions.
Speaker #5: With a refined strategy and strong clinical catalysts ahead, we remain confident in our position. We'll now open the call for questions.
Operator: Thank you. As a reminder, to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. One moment for questions. Our first question comes from Tyler Van Buren with TD Cowan. You may proceed.
Speaker #6: Thank you. As a reminder, to ask a question, please press *1 1 on your telephone and wait for your name to be announced. To withdraw your question, please press *1 1.
Speaker #6: Again, one moment for questions. Our first question comes from Tyler Van Buren with TD Cowen. You may proceed.
Speaker 9: Hey, thanks very much. I appreciate you taking the question and congrats on the progress during the quarter. So, as we think about the scheduled fertility analysis in the first half of next year, and since you announced that you plan to provide the rates of MRD conversion between the two arms at the time of the announcement, what does good look like as you think about the bar for success with the MRD conversion rates?
Speaker #7: Hey, thanks very much. I appreciate you taking the question, and congrats on the progress during the quarter. So, as we think about the scheduled fertility analysis in the first half of next year, and since you announced that you plan to provide the rates of MRD conversion between the two arms at the time of the announcement, what does good look like as you think about the bar for success with the MRD conversion rates?
David Chang: Hi, Tyler. Dave Chang here. Great question. And, you know, it's something that we have been thinking about quite a bit here. And so, you know, we have been asked this question a few times, and we've been giving a rough estimate about 30%. But now that we are beginning to talk about the MRD conversion rate in a more concrete way, let me give you some reference points about where we are coming to about the delta of 30% difference in the MRD conversion rate being meaningful. So here, you know, I would just ask you to sort of equate the MRD conversion to, you know, the remission, complete remission that you see, you know, with the CAR T treatment. And with that, you know, one assumption, you know, take the reference point to the USPI of Yescada and Brianzi.
Speaker #6: All right, Tyler. Dave Chang here. Great question. And, you know, it's something that we have been thinking about quite a bit here. And so, you know, we have been asked this question, you know, a few times, and we've been giving rough estimate about 30%, but now that we are beginning to talk about the MRD conversion rate and more, you know, concrete way, let me give you some, you know, reference point about where we are coming to about, you know, the delta of 30% difference in the MRD conversion rate being meaningful.
Speaker #6: So here, you know, I would just ask you to sort of equate the MRD conversion to, you know, the remission, complete remission that you see, you know, with the CAR-T treatment.
Speaker #6: And with that, you know, one assumption, you know, take the reference point to the USPI of Yes, CARTA and Brianzi. Both of them were approved in the second-line setting, you know, in a randomized study that used an event-free survival endpoint.
David Chang: Both of them are approved in the second-line setting, you know, in a randomized study that used event-free survival endpoint. In those studies, you know, Brianzi, you know, showed statistically significant and clinically meaningful event-free survival as well as progression-free survival benefit. And, you know, in that data set, if you look at the delta in the complete remission rate, that was 27%. Now, if you take the same to the Yescada USPI again, the ZUMA 7 study showed statistically significant and clinically meaningful event-free survival benefit as well as progression-free survival benefit. And in the follow-up, they also showed an overall survival benefit. And when you look at their initial indication of efficacy, which is really the response rate, the complete remission rate difference between the Yescada arm and the standard of care bone marrow transplant arm, that was 33%.
Speaker #6: In those studies, you know, Brianzi, you know, showed statistically significant and clinically meaningful event-free survival as well as progression-free survival benefit. And, you know, in that dataset, if you look at the delta in the complete remission rate, that was 27%.
Speaker #6: Now, if you take the same to the Yes, CARTA USPI, again, the Zoom at seven study showed statistically significant and clinically meaningful event-free survival benefit, as well as progression-free survival benefit.
Speaker #6: And in the follow-up, they also showed an overall survival benefit. When you look at their initial indication of efficacy, which is really the response rate, the complete remission rate difference between the CARTA arm and the standard of care, bone marrow transplant arm, that was 33%.
David Chang: So those are sort of the reference points that we are using to sort of guide about a delta of 30% difference in the MRD conversion rate could potentially give us a statistically significant and clinically meaningful benefit demonstration of the Alpha 3 study.
Speaker #6: So those are sort of the reference points that we are using to sort of guide about a delta of 30% difference in the MRD conversion rate, which could potentially give us a statistically significant and clinically meaningful benefit demonstration of the Alpha-3 study.
Operator: Thank you. Our next question comes from Byron Amin with Piper Sandler. You may proceed.
Speaker #2: Thank you. Our next question comes from Byron Amin with Piper Sandler. You may proceed.
Speaker 9: Yeah, hi. Thanks for taking my question. Maybe just to expand on the last question, how should we translate if we're able to see a 30% delta on MRD conversion? Should we expect similar EFS benefit to what was observed with Brianzi and Yescada in their respective trials in the second-line setting? And then the second question is on cash runway guide to the second half, I see to 2027. Do you anticipate having cash to get to EFS data readout from Alpha 3? Thanks.
Speaker #8: Yeah, hi. Thanks for taking my question. Maybe just to expand on the last question, how should we translate if we're able to see a 30% delta on MRD conversion?
Speaker #8: Should we expect similar EFS benefit to what was observed with Brianzi and yes, CARTA, and their respective trials in the second-line setting? And then second question is on cash, runway guide to the second half.
Speaker #8: I actually did a 2027. Do you anticipate having cash to get to EFS data readout from Alpha-3? Thanks.
David Chang: Hi, Byron. Let me take the first question, and I'll pass to Geoff for the second part. So the only thing that I ask from what I have responded to Tyler's question is if you equate MRD conversion to the CR or the complete remission that you see, which I believe is a fair, you know, sort of assumption that one can make, you know, the answer to your question is yes. And let me ask Geoff to comment on the cash guidance.
Speaker #6: Hi, Byron. Let me take the first question, and I'll pass it to Geoff for the second part. So the only thing that I ask from what I have responded to Tyler's question is if you equate MRD conversion to the CR, you know, the complete remission that you see, which I believe is a fair, you know, sort of assumption that one can make.
Speaker #6: you know, the answer to your question is yes. And, let me, ask Geoff to comment on the cash guidance.
Geoffrey Parker: Yeah, so Byron, as you stated, we do have cash into the second half of 2027. Whether that is sufficient to get to EFS readout on Alpha 3, frankly, depends on the pace of enrollment that we will see in the trial. And we'll be updating you on that once we have the futility analysis. As you recall, though, there is an interim analysis and a final analysis in the Alpha 3 study. And I would say second half of 2027 is going to be right in the ballpark as to when those events could occur.
Speaker #2: Yeah, so Byron, as you stated, we do have cash into the second half of 2027. Whether that is sufficient to get to EFS readout on Alpha-3, frankly, depends on the pace of enrollment that we will see in the trial, and we will be updating you on that once we have the fertility analysis.
Speaker #2: As you recall, though, there is an interim analysis and a final analysis in the alpha-3 study, and I would say the second half of 2027 is going to be right in the ballpark.
Speaker #2: As to when those events could occur. Thank you. Our next question comes from Salvine Richter with Goldman Sachs. You may proceed.
Speaker 9: Thank you.
Operator: Our next question comes from Salveen Richter with Goldman Sachs. You may proceed.
Speaker 9: Hey, this is Mark on for Salveen. Congrats on the quarter and thanks for taking our question. So kind of to expand on that, how is enrollment progressing for Alpha 3? You briefly mentioned this in the prepared rocks, but I was wondering if you can give any quantification. Is the discontinuation of the FCA arm in any way sort of impacting patient willingness to enroll and the enrollment cadence? Thanks.
Speaker #9: Hey, this is Mark on for Salvine. congrats on the quarter and thanks for taking our question. So kind of to expand on that, how is enrollment progressing for alpha-3?
Speaker #9: you briefly mentioned this in the prepared remarks, but I was wondering if you can give any quantification. Is the discontinuation of the FCA arm in any way sort of impacting patient willingness to enroll and the enrollment cadence?
Speaker #9: Thanks.
Zachary Roberts: Yeah, thanks, Markus and Zach. I will say that the momentum that we described at the last quarter continues to this day. There's a lot of interest in patients coming into the study. It's a little soon still to see how the discontinuation of FC may impact, sorry, FCA. Thank you, Christine. Discontinuing of FCA may impact the overall enrollment cadence. What I can say in these very early days post the discontinuation of that arm, we are generally getting positive feedback from investigators who are happy to be dealing with a regimen that they are much more comfortable with. And it's also, they've told us that it's easier in the conversations with the patients. They don't have to spend as much time talking about this additional agent that can induce the immunosuppression that is associated with CD52.
Speaker #2: Yeah, thanks, Mark. This is Zach. I will say that the, that, you know, the momentum that we described at the last quarter continues to this day.
Speaker #2: There's a lot of interest in patients coming into the study. It's a little soon still to see how the discontinuation of FC may impact, sorry, FCA.
Speaker #2: Thank you, Christine. Discontinuing of FCA may impact the overall enrollment cadence. What I can say in these very early days, post the discontinuation of that arm, we are generally getting positive feedback from investigators who are happy to be dealing with a regimen that they are much more comfortable with, and it's also they've told us that it's easier in the conversations with the patients.
Speaker #2: they don't have to spend as much time talking about this additional agent that can induce the immunosuppression that that is associated with CD52. So, I think signs are pointing to a positive impact to the study.
Zachary Roberts: So I think signs are pointing to a positive impact to the study. So we look forward to being able to update you further at the time of the interim analysis.
Speaker #2: We look forward to being able to update you further at the time of the interim analysis.
Speaker 9: Thank you.
Speaker #9: Thank you.
Operator: Thank you. Our next question comes from Kelly Xie with Jeffries. You may proceed.
Speaker #2: Thank you. Our next question comes from Kelly Shee with Jefferies. You may proceed.
Speaker 11: Congrats on the progress and thank you for taking my questions. I'm curious, actually, whether you see the timing of capturing MRD positive patients post RCHOP have any impact on the MRD conversion rate after the treatment and also maybe also the impact on EFS as the endpoint. And the second question is, if we take a step back, can you talk about the clinical evidence from your prior studies or maybe other historical studies? Like how was the efficacy bar set for the pivotal frontline consolidation studies? Thank you.
Speaker #10: Congrats on the progress, and thank you for taking my questions. I am actually curious whether you see the timing of capturing MRD-positive patients post R-CHOP having any impact on the MRD conversion rate?
Speaker #10: after the treatment and also maybe also the impact on EFS as the endpoint. And the second question is if we take a step back, can you talk about the clinical evidence from your prior studies or maybe other historical studies like how was the efficacy bar was set for the pivotal frontline consolidation study?
Speaker #10: Thank you.
David Chang: Hi, Kelly. I'm sort of smiling because that's a lot of questions and very insightful questions. You know, happy to have you sort of covering us again. You know, with respect to, you know, the timing of the MRD, you know, in the clinical study, we are doing it in very similar to how the retrospective study was done. You know, there is a defined window at which the MRD testing is done to make the patient eligible to the Alpha 3 study. And as for the MRD testing after SemaCell treatment, we have been saying, you know, this occurs, we don't, you know, about four to eight weeks after after SemaCell treatment is done. So again, you know, that is a similar time period to when one would carry out tumor assessment in a standard way.
Speaker #8: Hi, Kelly. I'm sort of smiling because there are a lot of questions. They are very insightful questions. You know, I’m happy to have you sort of covering us again.
Speaker #8: You know, with respect to the timing of the MRD, you know, in the clinical study, you know, we are doing it very similar to how the retrospective study was done.
Speaker #8: You know, there is a defined window at which the MRD testing is done to make the patient eligible for the Alpha-3 study.
Speaker #8: And as testing after semi-cell treatment, we have been saying, you know, this occurs within, you know, about four to eight weeks after after semi-cell treatment is done.
Speaker #8: So, you know, again, that is a similar time period to when one would carry out tumor assessment, you know, in the standard way for the MRD. So, the timing of the MRD, I don't think it will significantly impact, you know, what we're doing in the Alpha-3 study.
David Chang: So the timing of the MRD, I don't think it will significantly impact, you know, what we are doing in the Alpha 3 study.
Zachary Roberts: Yeah, and there's no data to just piggyback on David's point. There's no data, Kelly, to date to indicate that the timing of that MRD assessment will impact our ability to induce conversions. So, and similarly, we don't expect that to influence EFS. Those are fairly tightly correlated, MRD conversion and long-term disease control based on prior data from our MRD partner. And then I think the second question that you asked was around whether there's any prior data on MRD conversion and whether the bar that we are aiming for is aligned with that prior data. So I'll actually point back to David's answer to Tyler's question around what we think is going to be a clinically meaningful and significant outcome from Alpha 3, and that is around that 30% mark. There isn't really any data in large B-cell lymphoma looking specifically at MRD clearance in a prospective way.
Speaker #2: Yeah, and there's no data to just piggyback on David's point. There's no data, Kelly, to date to indicate that the timing of that MRD assessment will impact our ability to induce conversions.
Speaker #2: so, and, and similarly, we don't expect that to influence EFS, those are fairly tightly correlated MRD conversion and long-term disease control based on prior data from from our MRD partner.
Speaker #2: and then I think the second question that you asked was around whether there's any prior data on MRD conversion and whether the bar that we are aiming for is aligned with that prior data.
Speaker #2: So, I'll I'll actually point back to David's answer to Tyler's question around what we think is going to be a clinically meaningful and and significant outcome from alpha-3.
Speaker #2: And that is around that 30% mark. there isn't really any data in large B-cell lymphoma looking specifically at MRD clearance. in a prospective way, alpha-3 is really the the, the, the tip of the spear on this so we really are looking towards that second line post relapse setting to really set the bar for what efficacy could be.
Zachary Roberts: Alpha 3 is really the tip of the spear on this. So we really are looking towards that second line post-relapse setting to really set the bar for what efficacy could be. And we think that bar is certainly achievable with this strategy.
Speaker #2: And we think that bar is is certainly achievable with this strategy.
Speaker 11: Thank you. Super helpful.
Speaker #10: Thank you. Super helpful.
Operator: Thank you. Our next question comes from Jack Allen with Baird. You may proceed.
Speaker #2: Thank you. Our next question comes from Jack Allen with Baird. You may proceed.
Speaker 9: Great. Thank you so much for taking the questions and congrats again on all the progress. I guess I wanted to ask about how you're thinking about MRD conversion and its correlation with durability. I know a lot of the earlier stage data that you have from SemaCell included both the FC and the FCA arm. How much confidence do you have as it relates to the durability of remissions that you maybe see on this MRD test playing out as, you know, one-time cures here?
Speaker #9: Great. Thank you so much for taking the questions, and congrats again on all the progress. I guess I wanted to ask about how you're thinking about MRD conversion and its correlation with durability.
Speaker #9: I know a lot about earlier stage data that you have from Semicell, which included both the FC and the FCA arm. How much confidence do you have, as it relates to the durability of remissions that you maybe see on this MRD test, playing out as, you know, one-time cures here?
Zachary Roberts: Thanks, Jack. This is Zach again. So, you know, our belief, and based rooted in the data that is now sort of growing in the field around this MRD assessment, is that an MRD conversion going from positive to negative, you know, at the time point that we're performing the assessment is a very good correlate to long-term disease control. So that is why we analyzed this biomarker assessment to enable LD selection because we did believe that this was going to correlate tightly to EFS.
Speaker #2: Thanks, Jack. this is Zach again. So, you know, our our our belief and based rooted in the data that that is now sort of growing in the field around this MRD assessment is that that an MRD conversion going from positive to negative you know, at the time point that we're performing the assessment is a very good correlate to long-term disease control.
Speaker #2: So that is why we analyzed this biomarker assessment to enable LD selection, because we did believe that this was going to correlate tightly to EFS.
Speaker 9: And maybe can I just follow up? Are you going to look at any other internal metrics of durability other than MRD at the time of the interim? And then one brief follow-up on 329. I just wanted to think about the first half readout next year. What kind of patient numbers could you have there across the different diseases in the basket study?
Speaker #9: Right. And maybe I can just follow up? Are you going to look at any other internal metrics of durability other than MRD at the time of the interim?
Speaker #9: And then, one brief follow-up on 329. I just wanted to think about the first half readout next year. What kind of patient numbers could you have there across the different diseases in the basket study?
Zachary Roberts: So we will, as promised in our materials and in our prepared remarks, we will be giving you some detail around the MRD conversion, and we'll leave it at that for now. With respect to the question on 329, we've also not given specific numbers on what to expect, except to say that the study is open to enrollment currently, and we do expect to have a meaningful amount of data to share in the first half of next year.
Speaker #2: So So we will, as promised in our materials, and in our prepared remarks, we will be giving you some detail around the MRD conversion and and we'll leave it at that for now.
Speaker #2: With respect to the question on 329, we've also not given specific numbers on what to expect, except to say that, you know, the study is open to enrollment currently and we do expect to have a meaningful amount of data to share in the first half of next year.
Speaker 9: Thanks so much for the call.
Speaker #9: Thanks so much for the call-in.
Zachary Roberts: Thank you.
Speaker #2: Thank you. Our next question comes from Sammy Corwin with William Blair. You may proceed.
Operator: Our next question comes from Sammy Corwin with William Blair. You may proceed.
Speaker 11: Hi, congrats on the progress, and thanks for taking my questions. I know previously when we've spoken, you guys were initially hesitant to do the MRD analysis with the futility analysis or share that information because you were concerned that sharing the MRD conversion rates could influence the behavior of treating physicians. So I guess I'm curious how your thoughts around that have kind of evolved and how that might ultimately impact the difference in overall survival between the two arms. And then looking at the LO329 data, should we expect to see data from both lymphodepletion groups? Thank you.
Speaker #10: Hi, congrats on the progress and thanks for taking my questions. I know previously when we've spoken, you guys were initially hesitant to do the MRD analysis with the fertility analysis or share that information because you were you were concerned that sharing the MRD conversion rates could influence the behavior of treating physicians.
Speaker #10: So, I guess I'm curious how your thoughts around that have kind of evolved and how that might ultimately impact the difference in overall survival between the two arms.
Speaker #10: And then looking at the Allo329 data, should we expect to see data from both lymphodepletion groups? Thank you.
David Chang: Yeah, so Sammy, David Chang here. You know, the great question. Yes, we do have a lot of sensitivity in the amount of the efficacy data that we can share. You know, the Alpha 3 study, it uses the event-free survival as the primary endpoint. So in that sense, the MRD conversion is a secondary biomarker-based data. And in the large B-cell lymphoma, yes, there are some data that seem to correlate the MRD conversion to the durability of the response, but that has not been prospectively tested, especially in patients whose only evidence of disease is MRD positivity. So, you know, there are certain caveats, and we're trying to, you know, walk the fine balance.
Speaker #8: Yeah, so Sammy, David Chang here. You know, the great question. Yes, we do have a lot of sensitivity in the amount of the efficacy data that we can share.
Speaker #8: you know, the alpha-3 study, it uses the event-free survival as the primary endpoint. So in that sense, the MRD conversion is a secondary biomarker-based data.
Speaker #8: And in large B-cell lymphoma, yes, there are some data that seem to correlate the MRD conversion to the durability of the response, but that has not been prospectively tested.
Speaker #8: Especially in patients who only evidence of disease is MRD positivity. So, you know, there are certain caveats and we're trying to, you know, walk the fine balance, but from the fact that we are limiting the data communication at the interim fertility analysis to MRD conversion, you know, we believe that you know, we can still maintain the the, you know, the, you know, the, you know, balanced way as we, you know, continue to enroll additional patients after the, you know, fertility analysis.
David Chang: But from the fact that we are limiting the data communication at the interim futility analysis to MRD conversion, you know, we believe that, you know, we can still maintain the, you know, the balanced way as we continue to enroll additional patients after the futility analysis. I think the clinical equipo would not be compromised by sharing the secondary biomarker data on a limited number of patients. With respect to LO329 data communication in the first half of next year, let's just say that we are focusing on biomarker as well as early clinical data. And as you know, the study is progressing in two different lymphodepletion regimens, starting with the cyclophosphamide-only lymphodepletion, which already is a reduced lymphodepletion compared to the standard buldarban and cyclophosphamide. However, in addition to that, we are also testing no lymphodepletion in a parallel cohort.
Speaker #8: I think the clinical equipoise would not be compromised by sharing the, you know, secondary biomarker data on a limited number of patients. With respect to Allo329, data communication in the first half of next year, let's just, you know, say that we are focusing, you know, on biomarker as well as early clinical data.
Speaker #8: And as you know, the study is progressing with two different lymphodepletion regimens, starting with the cyclophosphamide-only lymphodepletion, which already is a reduced lymphodepletion compared to the standard fludarabine and cyclophosphamide.
Speaker #8: However, in addition to that, we are also testing no lymphodepletion in a parallel cohort. So, we'll provide more updates on exactly what how much will be included in the first half, 2026 update as study progresses.
David Chang: So we'll provide more updates on exactly how much will be included in the first half of 2026 update as the study progresses.
Speaker 11: Great, thank you.
Speaker #10: Great, thank you.
Operator: Thank you. Our next question comes from Matt Biegler with Oppenheimer. You may proceed.
Speaker #2: Thank you. Our next question comes from Matt Biegler with Oppenheimer. You may proceed.
Speaker 9: Hey guys, thanks for the update. I've had a lot of questions on MRD, but we haven't had any on cell expansion. So I'm just wondering, like, has your thinking changed now that you're in a lower tumor burden setting on the importance of cell expansion? Is it not as relevant as it was in a higher disease setting? Because looking back to 2022, your R&D event, the push for 647 really was that it improved cell expansion. So I'm just kind of trying to make sense of where we are now that we're in a different disease setting. Thanks.
Speaker #11: Hey, guys. Thanks for the update. I had a lot of questions on MRD, but we haven't had any on cell expansion. So, I'm just wondering, has your thinking changed now that you're in a lower tumor burden setting on the importance of cell expansion?
Speaker #11: Is this not as relevant as it was in a higher disease setting? Because, you know, looking back to 2022, your R&D event, the push for 647 really was that it improved cell expansion.
Speaker #11: So, I'm just kind of trying to make sense of where we are now that we're in a different disease setting. Thanks.
David Chang: Yeah, Matt, Dave Chang again. Let me take that question. I don't think it's really changing our thinking. As Zach had made a comment in his prepared statement, we knew that as we started Alpha 3 study, we are going into a different clinical setting of the extremely low-volume disease setting where the antigen target, which is really what triggers the cell expansion, is at the lowest possible level that one can think about. So we had a very open-minded approach about in that kind of setting, what degree of cell expansion would be optimal to eradicate MRD positivity. And the conclusion that we drew at the time is that the approach that we have made in the relapse refractory setting, so these are the patients with the bulky disease where we felt cell expansion as well as persistence is really important. We cannot think the same way.
Speaker #8: Yeah, Matt, David Chang again. Let me take that question. I don't think it's really changed in our thinking. As you know, Zachary Roberts had made a comment in his prepared statement.
Speaker #8: We knew that as we, you know, started alpha-3 study, you know, we are going into a different clinical setting. the, you know, extremely low volume disease setting.
Speaker #8: where the antigen target, which is really what triggers the cell expansion, is at the lowest possible level that one can think about. So we had a very open-minded approach about, in that kind of setting, what degree of cell expansion would be optimal to eradicate MRD positivity.
Speaker #8: And, you know, the conclusion that we drew at the time is that the approach we have made in the relapse refractory setting—so these are the patients with bulky disease—where we felt cell expansion as well as persistence is really important.
Speaker #8: You know, we cannot think the same way. And, you know, that was how the genesis of the alpha-3 study starting with the 3 arm.
David Chang: And that was how the genesis of the Alpha 3 study, starting with the three arm, not only testing FCA but also testing FC. So obviously, at this point, we have some idea, as we have previously communicated, through the unplanned data analysis, MRD conversion being seen in the FC. So at this point, really, let's just stay tuned. I mean, we will know more in the next six months.
Speaker #8: Not only testing FCA, but also testing FC. So, obviously at this point, you know, we have some idea, as we have previously communicated through the unplanned data analysis, you know, MRD conversion being seen in the FC.
Speaker #8: So, at this point, really, let's just stay tuned. I mean, we will know more in the next six months.
Speaker 9: Makes sense. Thank you.
Speaker #11: Makes sense. Thank you.
Operator: Thank you. Our next question comes from Samantha Simmenthau with City. You may proceed.
Speaker #2: Thank you. Our next question comes from Samantha Semenko with City. You may proceed.
Speaker 11: Yes, ma'am. I'm sorry to interrupt your question. I recalled the mass study you had earlier this month that there was a possibility that.
Speaker #10: I'm sorry. Are the cells in the last title you had earlier this month or early this month?
David Chang: Can you speak up a little bit? It's coming out a little bit muffled.
Speaker #8: Can you speak up a little bit? It's coming out a little bit muffled.
Speaker 11: Oh, apologies. Is this better?
Speaker #10: Oh, apologies. Is this better?
David Chang: Yes.
Speaker #8: Yes.
Speaker 11: Perfect. So thank you for taking the question. I recall in this call earlier this month that there was a protocol amendment to close the FCA arm. And I'm wondering if that has been considered as well as are you able to continue the enrollment into the FCA while that protocol amendment is undergoing? And back into the prior response to your question, you said that there's a defined period of MRD positivity where the patient could be eligible for enrolling in a study and wondering if there's any overlap with that window and some patients might be missing it and not being able to enroll in a study. Thanks very much.
Speaker #10: Perfect. so I say thank you for taking the question. I recall in the spring, there was a call earlier this month that there was a protocol amendment to close the FCA arm and and I'm wondering if that has been completed and as well as is are you able to continue enrollment into the FC arm while that protocol amendment is underway?
Speaker #10: I'm asking because in the prior response to your question, you said that there's a defined period of MRD conversion or MRD positivity during which the patient could be eligible for enrollment in a study and, in amending, if there's any overlap with that window, some patients might miss it and not be able to enroll in the study.
Speaker #10: Thanks very much.
Zachary Roberts: So, sorry, Samantha, it was still quite muffled. I think I got the first part of your question, and I'll answer that, and then maybe you can try to fix your connection and ask the second part because that one was a little harder to understand. The first question was around the status of enrollment as the operational implementation of the closure of the FCA arm is underway. So the patients are continuing to be screened for MRD. The protocol amendment that enabled us to close the FCA arm earlier than anticipated is with IRBs currently. We expect that protocol amendment to be approved in the next few days. So we anticipate very little, if any, disruption to the operations of this trial as a result of this amendment. And then maybe you can ask the second part again.
Speaker #2: So, so sorry, Samantha. It was still quite muffled. I think I got the first part of your question, and I'll answer that, and then maybe you can try to fix your connection and ask the second part because that one was a little harder to understand.
Speaker #2: The first question was around the status of enrollment as the operational implementation of the closure of the FCA arm is underway.
Speaker #2: So the patients are continuing to be screened for MRD. The protocol amendment that enabled us to close the FCA arm earlier than anticipated is with IRBs currently.
Speaker #2: We expect those that a protocol amendment to be approved in the in the next few days. so we anticipate very little, if any, disruption to the operations of this trial for and as a result of this amendment.
Speaker #2: And then maybe you can ask the second part again.
David Chang: Yes, hopefully you're able to hear me now. Apparently, my Bluetooth has been-.
Speaker #10: Yeah, so hopefully you're able to hear me now. Apparently, my speaker cut out; Bluetooth headphones were causing some issues. So, yeah, I think I think you answered most of the questions.
Speaker 9: Yes, I see your voice better. Thank you.
David Chang: --bluetooth has been causing some issues. So yeah, so I think you answered most of the question. Just confirming that once this IRB approval comes through in a few days, all of the patients that were screened in the interim are still eligible to enroll into the FCA arm.
Speaker #10: Just confirming that once this IRB approval comes through in a few days, all of the patients that were screened in the interim are still eligible to enroll in the FC arm.
Zachary Roberts: Yes, absolutely.
Speaker #2: Yes, absolutely.
David Chang: Understood. Thanks very much for the question.
Speaker #10: Understood. Thanks very much for the question.
Operator: Thank you. Our next question comes from Luca Acey with RBC Capital Markets. You may proceed.
Speaker #2: Thank you. Our next question comes from Lucas. Luca, is he with RBC Capital Markets? You may proceed.
David Chang: Oh, great. This is Shelby on for Luca, and thanks for taking the question.Maybe
Speaker #12: Oh, great. This is Shelby on for Luca, and thanks for taking the question. Maybe circling back on a prior question on enrollment, we appreciate that the depth that you guys reported a couple of weeks back was likely related to Allo647, which you're obviously no longer pursuing.
Operator: circling back on a prior question on enrollment, we appreciate that the death that you guys reported a couple of weeks back was likely related to ALICE 647, which you are obviously no longer pursuing. However, this is also the first time you're reporting a death in the first-line maintenance setting for a patient that was otherwise relatively stable post-RCHOP versus, I believe, the other deaths that you reported in the past were in patients with much more refractory disease, like the three deaths reported in multiple myeloma. So I guess the question is, is this event going to slow down enrollment materially, or do you think this is a non-event for enrollment velocity? Any color there, much appreciated. Thanks.
Speaker #12: However, this is also the first time you're reporting a death in the first-line maintenance setting for a patient that was otherwise relatively stable post R-CHOP.
Speaker #12: Versus, I believe the other deaths that you reported in the past were in patients with much more refractory disease, like the three deaths recorded in multiple myeloma.
Speaker #12: So I guess the question is, is this event going to slow down enrollment materially, or do you think this is a non-event for enrollment velocity?
Speaker #12: Any color there? Much appreciated. Thanks.
Zachary Roberts: Thanks, Shelby. Good question and absolutely part of the analysis when we wrote the study. And then in the immediate wake of this unfortunate grade five event, we asked ourselves that very question. We discussed it with all of the external stakeholders like the DSMB, the steering committee, and the FDA. And the consensus was really quite clear that these patients, you know, you characterize them as relatively stable. You know, I think the data would strongly indicate that these patients have chemo-refractory cancer. And we know from the MRD data that these patients are going to progress and likely to progress very soon. So the investigators, the patients who consider enrolling this trial, see themselves not as in remission and likely to never hear from their cancer again. They actually, I think, appropriately see their situation as extremely high risk and worthy of enrollment into a clinical trial.
Zachary Roberts: That said, a grade five event like the one that we observed is a significant moment in any clinical trial, this one included. And that was what prompted us to take a look at the overall safety data as well as that MRD conversion data that we referred to. And at that point, we really had the confidence that moving forward with the FCRM would deliver the appropriate benefit risk for the patients in this particular clinical setting. So all of us looked at the data and we all think that this, investigators included, is worth pursuing.
Operator: Got it. Thanks.
Operator: Thank you. Our next question comes from Astaga Gundwordin with Truist. You may proceed.
Got it, thanks.
Thank you.
Operator: Hey, guys. Thanks for taking the question. I probably want to just jog my memory here a bit. And if I remember right, some of the earliest selective data showed that early reconstitution of the patient's T cells was what was correlated with poorer response. And that's what rationalized the use of CD52 antibody back in the day. But that was also in a leukemia setting as well as in a late line setting. So to ask the question again, but more focused on the endogenous T cell population, is the early line setting and also post-RCHOP, does that change the dynamics here of what could predicate a poorer response? And then I have a quick follow-up.
Our next question comes from a good wording with Truist. You may proceed.
Hey guys, thanks for taking the question. Um a problem just uh jog my memory here a bit and if I remember right some of the earliest selective data showed that early, reconstitution of the patients T cells but what was what was uh correlated with poorer response? And that's what rationalized the use of cd52 antibody back in the day. Um, but that was also in in, you know, the genius setting as well as in a late line setting. So to ask the question again and but, but more focused on the endogenous T Cell population is the earlier line setting and also post Art Shop. Uh, does that change the Dynamics here of of of what could, uh, predict a poor response and that I have a quick follow up.
David Chang: Yeah, David Chang, let me give Zach a break and take your question. In terms of the early selective data, I think you are remembering it correct. I mean, certainly in the relapse refractory setting, most of the data from selective is coming from the ALL study that was carried out. There was definitely an indication that adding anti-CD52 antibody leads to a more prolonged cell expansion. Having said that, even with the FC regimen, there always has been some degree of cell expansion. And that's always something that we have known. So it's really trying to thread the right needle that fits the clinical indication that we are going after. If we are going after a bulky disease setting, I would have a lot of discomfort in limiting the lymphodepletion with FC alone. But as we have said, MRD positive is a very unique clinical setting.
Uh, yeah, they changed. Let me, uh, give Zach a break and take your question. Um, in terms of, uh, the early Sylectus data, I think, you know, you, uh, uh, remembering it, correct. I mean, certainly, uh, in the relapse refractory setting, uh, most of the data from Sylectus is coming from the ALLL study that was carried out. Uh, there was definitely an indication that adding anti-CD52 antibody leads to a more prolonged cell expansion.
David Chang: On one hand, it clearly foretells that the patient will have a disease recurrence. But on the other hand, the level of disease that's in the patient's body is not detectable by conventional PET/CT scan. It is at the molecular level of disease burden, which is the objective of the Alpha 3 study, trying to eradicate that minimum of disease. So this is a lot different clinical setting. And the kind of cell expansion or persistence that most people are thinking about doesn't really apply. And as I said, that always has been one of our hypotheses as we are embarking on Alpha 3 study.
Having said that even with the FC regimen, you know, there always has been some degree of self expansion and that's always, you know, something that we have known. So it's really, you know, trying to thread the right needle, uh, that fits the clinical indication that we are going after. If we are going after, you know, bulky disease setting, I would have a lot of, uh, discomfort in limiting, the lympo depletion, uh, with FC alone. But as we have said, you know, mrd positive is a very unique clinical setting, you know, on 1 hand, it clearly foretells that the patient will have a disease recurrence, but on the other hand, the level of disease that's in the patient's body is not detectable by conventional PET, CT scan. It is at the molecular level of of, you know, disease burden which which is the objective of the alpha 3 study trying to eradicate that in a minimum of disease. So this is a
Operator: Thanks, David. And then the quick follow-up here is, when you talk about the MRD conversion rates early next year, will you also be in a position to give color on the mix of patients that came from community versus academic, as well as those who are treated inpatient versus outpatient? Or would that be too early to comment on that? Thanks.
Of persistence that most people are thinking about, you know, doesn't really apply. And, as I said, that always has been one of our hypotheses as we are embarking on the Alpha 3 study.
David Chang: I mean, certainly in terms of patient distribution, I don't see any reason to withhold that information. It may be in a limited number of patients. I mean, because the futility analysis is based on 24 patients. So having said that caveat, I mean, we are trying to make that communication as informative to you analysts as well as the investors.
Thanks, David. Um, and then the quick follow-up here is, um, when you talk about the MRI conversion rates early next year, will you also be in a position to give color on the mix of patients? That came from community versus academic, as well as those who are treated inpatient versus outpatient, or would that be too early to comment on that? Thanks.
Uh, I mean, certainly in terms of...
You know, I don't see any reason, uh, to withhold that information. You know, it may be, you know, limited number of patients. I mean, because the futuria analysis is based on 24s. So, uh, having said that caveat, I mean, we are trying to make that communication as informative to, uh, you analysts as well as the investors.
Operator: Thank you. Our next question comes from William Pickering with Burns Lean. You may proceed.
Thank you.
David Chang: Hi. Thank you for taking my question and congrats on the continued progress. For the interim analysis, are you able to share any of the quantitative criteria to run that, such as minimum number of events or minimum duration of follow-up? And how sensitive are those assumptions or criteria to the observed MRD conversion rate that you'll share early next year? Thank you.
Our next question comes from William, Pickering, with Bern City. You may proceed.
Hi. Thank you for taking my question, and congrats on the continued progress. Um, for the interim analysis, are you able to share any of the quantitative criteria to run that, such as minimum number of events or minimum duration of follow-up, and, uh, how sensitive are those assumptions or criteria to the observed MRD conversion rate that you'll share early next year? Thank you.
Zachary Roberts: Hey, William. This is Zach. So you know we don't think that the MRD conversion rate that we intend to share is going to be terribly sensitive to some of those aspects that you highlighted. The protocol describes an MRD assessment at a specific time point. And so we collect that test at that time. And then we analyze whether it's positive or negative. And that's the data that we intend to share.
Hey, William. This is Zach. So, um, you know we don't think that the MRD conversion rate that we intend to share is going to be terribly sensitive to some of those aspects that you highlighted regarding the protocol.
David Chang: Thank you.
Describes an MRD assessment at a specific time point. And so you know, we collect that test at that time, and then we analyze whether it's positive or negative, and that's the data that we intend to share.
Operator: Thank you. Our next question comes from Rennie Benjamin with Citizens. You may proceed.
Thank you.
Thank you.
Zachary Roberts: Hey, good afternoon, guys. Thanks for taking the questions. With 329, I guess I'd love to get a better understanding and additional color on how you picked the just the cyclophosphamide regimen and why not have maybe a three-arm study with FC, just cyclophosphamide, and then no lymphodepletion. So what's leading you to this? And then as a follow-up, what kind of proof of concept data do you think you need to see in order to move the program forward, especially given other cell therapy players that have generated data in the autoimmune space? Thank you.
Our next question comes from Renie Benjamin with Citigroup. You may proceed.
Hey, good afternoon, guys. Thanks for taking the questions. Um, with 329, I guess I'd love to get a better understanding and additional color on how you picked.
Uh, just the Cyclops ID regimen. Um, you know, and, and, and why not have maybe a three-arm study with FC, just cycle FM and then no lymph depletion. So, so what's leading you to this? And then?
David Chang: Hey, Brian. David here. So let me take the first question about why we chose cyclophosphamide. In the autoimmune disease indication, I mean, we do believe that we have to think about a little bit differently when it comes to the benefit-risk profile, especially the risk profile. Taking away fludarabine provides a lot of additional safety benefits. And then second, cyclophosphamide as a chemotherapy agent is something that many rheumatologists are very comfortable with since it often gets used to treat severe lupus or other autoimmune disorders. And sort of embedded in your question is, is cyclophosphamide going to be enough? This one, I would sort of point you to the earlier studies that were published from Fred Hutch, where they have looked at a comparison of cyclophosphamide and fludarabine. So what was very clear from that presentation was that cyclophosphamide alone is good enough to give the cell expansion.
As a follow-up, what kind of proof-of-concept data do you think we need to see, uh, in order to move the program forward, especially given, you know, other cell therapy players that have generated, um, data in the autoimmune space? Thank you.
Hey Brian. Uh, David here. So, let me take the first question about, you know, why we chose psychopath in the autoimmune disease indication? I mean, you know, we do believe that we have to think about little bit differently when it comes to the benefit risk profile. Especially the risk profile, uh, taking away through the Arabian. Uh provides a lot of um, you know, additional safety benefits. And then second uh, psychopath might, you know, as a chemotherapy agent is something that many rheumatologists that are very comfortable with, since it's some, you know, not off it, it pre, it often gets used to treat uh severe uh lupus or other autoimmune disorders. And, you know, sort of embedded in your question is, is Cyclops. Am I going to be enough?
David Chang: However, the durability of cell expansion is not as great. Really, the durability comes from by the addition of the fludarabine. So for the autoimmune indications, really the objective is to achieve deep B-cell depletion without prolonging it. So from that sense, we felt cyclophosphamide alone would be a much better fit for autoimmune indications.
Uh, this, you know, I would sort of, uh, point you to the earliest studies, uh, that were published from Fred Hutch, where they have looked at a comparison of psychopathy and, uh, psychopath might. And so what was very clear from, you know, that, uh, presentation was that psychopaths were might alone is good enough to give the cell expansion. However, the durability of cell expansion is not as great. Um, you know, really, the durability comes from, you know, by the addition of the, you know, fluid Darien, so for the autoimmune indications, you know. Really, the objective is to achieve deep piece of depletion, uh, without prolonging it. So from that sense, we felt sacrifice psychopath might alone would be a much better fit for autoimmune indications.
Zachary Roberts: Got it. And just as you see that data, that proof of concept data, what are you looking for in order to kind of get that go/no-go decision, make that go/no-go?
David Chang: I think ultimately we will have to look at the clinical data. But leading to clinical data, there's a lot of good indicators. After all, the objective of at least CD19 part of ALL 329 is B-cell depletion. So the degree of B-cell depletion and more importantly, how they're returning B cells, what are their phenotype, I think that those are very important information. And somewhat associated with that is disappearance of autoimmune antibodies. And those are things that have consistently been observed with the autologous CAR T that have been tested in the autoimmune indications. Certainly, that will give us a lot of information. And ultimately, as we follow those patients, their clinical response, whether they continue to require other anti-autoimmune medications, whether their symptoms go away, I think all those things can be told relatively quickly.
Got it. And and just, you know, as you as you see that, see that data, um, that proof of concept data. What? What, what are you looking for? Um, in order to kind of get that go no-go decision make that go, no, I, I think, you know, ultimately, you know, we will have to look at, you know, the clinical data. But leading to clinical data, there's a lot of good indicators. Uh, after all the objective of at least, cd19 part of all 329 is B cell depletion. So the, the degree of B cell depletion and more importantly, you know, how the returning B cells. What are their phenotype? I think that those are very important information and, uh, some might Associated, uh, with that is, uh, disappearance of autoimmune antibodies. And those are things that have consistently been observed, uh, with the alus carti that have been tested in the autoimmune indications, uh, certainly, they will give us a lot of information and ultimately, as we follow those
Zachary Roberts: Got it. Thank you.
Patients, you know, they are, you know, clinical response, whether they continue to require other, uh, autoimmune medications, uh, whether their symptoms go away. I think all those things, uh, can be told, uh, relatively quickly.
David Chang: Thank you.
Got it. Thank you.
Thank you.
Operator: And our last question comes from Brian Chang with JPMorgan. You may proceed.
David Chang: Hi, David. Thanks for taking our question this afternoon. I just want to follow up on your bar for success in Alpha 3 earlier. The 30% delta reference, I think you and Zach mentioned, they seem to be coming from the later line setting. I think the trials that you quoted, they're coming from the later line trials. So how is this bar, the 30% conversion bar, a fair translation in this consolidation line that you're shooting for after RCHOP or RCHIP? Shouldn't we expect a higher bar when you're looking into an earlier line? Thank you.
And our last question comes from Brian, Jane with JP Morgan. You may proceed.
David Chang: Yeah, Brian, great question. Frankly, the information that I cited is really coming from the second-line randomized study that was conducted with Yescata and Brianzi. And I think this is, in my view, a very good reference point. As long as you equate MRD conversion to the CR that you can detect with a PET/CT, as long as you accept that premise, I think the sort of the analogy or the reference point about what bar would be sufficient to get to a statistically significant as well as clinically meaningful benefit on the EFS and PFS, I think this is a really good reference point for ones to think about. And certainly, the ultimate test is the outcome of Alpha 3 study.
Hi, David. Thanks for taking a question, this afternoon. Uh, I just want to follow up on your bar for success in Alpha 3, uh, earlier. Um, the 30% Delta reference, I think you and Zach mentioned. Um they they seem to be coming from the later line setting. I think the the trials that you quoted um they're coming from the later line trials. So, how is this bar? The 30% conversion bar, a fair translation in this consolidation line that you're showing for after our talk or our chip. Um, shouldn't we expect a higher bar when you're looking into early in line? Thank you.
Yeah, Brian, uh, you know, a great question, you know, frankly, you know, the, the, the information that I cited is really coming from the second line, uh, randomized study. That was conducted with yesca and brillanti. And, uh, I think these, this is a, you know, in my view, you know, in a very good reference point.
Uh, as long as you equate mrd conversion to the the, the CR, you know that you can, you know, detect with a PET CT, as long as you accept that premise. I think, you know, you know, the sort of the analogy or the reference point about, you know, what bar would be sufficient to get to, you know, in a statistically significant as well as clinically meaningful uh, benefit on the EFS. And PFS I think, you know, this is a really good reference point for ones to think about and certainly um, you know the the ultimate test is the outcome of alpha 3 study.
Operator: Thank you. That concludes our question and answer session. I would like to turn the conference back over to management for any additional comments.
Thank you.
David Chang: All right. Thank you. As we reflect on this past quarter, it's clear that Allergen is entering a new chapter, one defined by operational clarity and growing clinical momentum. With Alpha 3, we made a decisive move to streamline the study, enhancing patient safety while preserving the trial's scientific integrity and simplifying the regulatory path. With ALL 316, we've reached alignment with FDA on the pivotal trial path, an important step for what we believe is the most advanced allogeneic CAR T program in cell tumors. And with ALL 329, we've officially launched Resolution Study, our first foray into autoimmune disease, with a study that could redefine how cell therapy is applied in immune-mediated conditions. These are not incremental steps. They are true inflection points, with each one accelerating our path towards a future where allogeneic CAR T is not only possible but the standard of care.
That concludes our question-and-answer session. I would like to turn the conference back over to management for any additional comments.
All right. Thank you. As we reflect on this past quarter, it's clear that Allogene is entering a new chapter defined by operational clarity and growing clinical momentum.
With Alpha 3, we made a decisive move to streamline the study, enhancing patient safety while preserving the trials, scientific integrity, and simplifying the regulatory path.
Without a 316, we've reached alignment with the FDA on the pivotal trial path. An important step for what we believe is the most advanced allergenic CAR-T program in solid tumors. And with Allo-3 to 9, we've officially launched the Resolution Study, our first foray into autoimmune disease, with a study that could redefine how cell therapy is applied in immune-mediated conditions.
These are not incremental steps.
David Chang: Our upcoming milestones are value-driving catalysts that have the potential to reshape the landscape of cell therapy and define Allergen's leadership in the field. Thank you for your continued interest and support. We look forward to connecting with many of you in upcoming meetings and events in the month ahead. Operator, you may now disconnect.
We are true; they are true inflection points with each 1 accelerator, where allergenic car key is not only possible but the standard care.
Our upcoming milestones are valued driving catalysts.
That have the potential to reshape the landscape of cell therapy and define Allergens' leadership in the field.
Operator: Thank you. Ladies and gentlemen, thank you for your participation in today's conference. This does conclude the program. And you may now log off and disconnect.
Thank you for your continued interest and support. We look forward to connecting with many of you in upcoming meetings and events in the month ahead. Operator, you may disconnect.
Ladies and gentlemen, thank you for your participation. In today's conference, this does conclude the program, and you may now log off and disconnect.