Hello. Thank you for standing by and welcome to Allogene Therapeutics ALPHA3 trial update. At this time, all participants are in the listen-only mode. After the speaker's remarks, there will be a question and answer session. To ask a question during this session, you would need to press the star one one on your telephone. You would 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 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.
Thank you, operator, and thanks to all of you for joining us on the call this morning. Today, before market open, Allogene Therapeutics issued a press release that provided an update on our ALPHA3 trial. That press release and this webcast are available on our website. Following prepared remarks by Dr. David Chang, President and CEO, and Dr. Zachary Roberts, Executive Vice President of R&D and Chief Medical Officer, we'll open the line for a focused Q&A. While we'll aim to keep the call concise, it's a Friday morning. We welcome your questions and appreciate your engagement. During today's call, we will be making certain forward-looking statements.
These may include statements regarding the success and timing of our ongoing and planned clinical trials, data presentations, regulatory filings, future research and development efforts, manufacturing capabilities, the safety and efficacy of our product candidates, commercial market forecasts, and financial guidance, among other things. These forward-looking statements are based on current information, assumptions, and expectations that are subject to change. A description of potential risks can be found in our press release and latest SEC disclosure documents. You are cautioned not to place undue reliance on these forward-looking statements, and Allogene Therapeutics disclaims any obligation to update these statements. I'll now turn the call over to David.
Thank you, Christine. Today, we are providing an important update on our ALPHA3 study of Cema-Cel in first-line consolidation for large B-cell lymphoma. We have taken decisive steps that we believe will ultimately improve patient safety, streamline our clinical development path, and potentially support adoption in the long term for community cancer centers. In close consultation with the ALPHA3 DSMB and steering committee, as well as discussion with the FDA , we have elected to move forward with standard fludarabine and cyclophosphamide as sole lymphodepletion regimen in the study. As a result, the FCA arm, which includes ALLO-647, has been closed. This decision follows a grade 5 adverse event in a patient who had received FCA lymphodepletion. The individual developed a fatal adenoviral hepatitis. While Cema-Cel was not implicated, the immune suppression associated with ALLO-647, an anti-CD52 monoclonal antibody, likely contributed to the outcome.
The decision to enroll in a clinical study can be a difficult one, and we are grateful for the trust patients place in us in making that decision. This is an outcome we do our utmost to avoid, and we offer our deepest sympathies to the family. Following the event, we conducted an unplanned review of safety and biomarker data. The findings indicate an encouraging MRD conversion and a supportive safety profile in the standard FC arm, giving us confidence that a prolonged lymphodepletion is not needed to clear minimal residual disease. From this point forward, the ALPHA3 trial will proceed with a streamlined two-arm trial comparing Cema-Cel after standard FC lymphodepletion versus observation. The planned futility analysis remains on track for the first half of 2026. Importantly, this represents more than an update to ALPHA3. It signals a strategic evolution in Allogene 's approach.
For ALPHA3 specifically, we believe that retiring ALLO-647 enhances the safety, simplicity, and scalability of our trial design and long-term product vision. More broadly, ALLO-647 is no longer included in any trial open for enrollment or pipeline program. Instead, our efforts are focused on advancing next-generation AlloCAR-T product candidates powered by our Dagger platform technology. Dagger is designed to minimize or even eliminate the need for standard lymphodepletion, something we believe is key to unlocking broader access to CAR-T. That vision is already reflected in programs like ALLO-316 and ALLO-329, where Dagger technology is helping reshape expectations for solid tumors and autoimmune disease. With that, I will turn over to Zach.
Thank you, David. As David noted, the decision to close the FCA arm was made as a result of a patient who developed rapid and severe liver inflammation and failure due to systemic adenovirus infection. Adenovirus infection is typically associated with mild and localized symptoms, but in patients with low T-cell counts, it can develop into severe disease. The patient initially presented approximately seven weeks after receiving Cema-Cel with mild symptoms, which then rapidly progressed despite aggressive measures. This rapid deterioration was attributed to the prolonged immunosuppression associated with the monoclonal antibody ALLO-647-based lymphodepletion and not the cell therapy itself. In the wake of that event, we moved swiftly to evaluate safety and biomarker data from the trial to ensure the safety of future study participants, as well as to confirm preliminary evidence of benefit.
The findings from this unplanned review, which indicate encouraging MRD conversion and supportive safety profile in the standard FC arm, supported early closure of the FCA arm and progression with the trial with no other changes. While early, the data strengthens our confidence in moving forward with the standard FC lymphodepletion, a regimen that we believe investigators trust and patients can access more safely and conveniently. Since communicating this to investigators, we've received encouraging feedback that streamlining the study quickly in response to this event may bring benefit to the trial. This decision prioritizes patient safety by reducing the risks associated with deep immunosuppression associated with CD52 antibodies, simplifies the trial conduct, and gives our patients a simpler regimen, one that aligns more closely with how they want to treat patients in the real world.
During this time, pre-screening and MRD testing has continued at the encouraging pace we've seen since earlier this year. As of today, our footprint includes over 50 activated sites across the U.S. and Canada, and we are preparing to open additional international sites. We believe the decision we've made in response to this unfortunate event not only puts patient safety first, but also preserves the scientific integrity of ALPHA3 while potentially enhancing its operational strength and real-world relevance. The trial is now uniquely positioned to answer a pivotal clinical question: can a single off-the-shelf CAR-T infusion delivered early when the disease burden is low and paired with a trusted lymphodepletion regimen alter the trajectory of disease for high-risk LBCL patients? We are more confident than ever that the answer to that question is yes.
Our commitment to advancing this trial has never been stronger, and our path forward is now better defined, more efficient, and more closely aligned with current practice, which ultimately will help us deliver on Allogene 's mission to bring the promise of CAR-T cells to patients in need. I'll now turn the call back to David.
Before we address your questions, I want to take a moment to underscore what today's update represents for Allogene Therapeutics and for the ALPHA3 program. The actions we have taken reflect a clear and confident path away from ALLO-647, a component that introduced complexity, and towards a trial design that we believe is cleaner, safer, and more aligned with the needs of both investigators and patients. Importantly, the ALPHA3 protocol retains its statistical integrity and streamlines the regulatory pathway. That gives us the opportunity to reach more patients more quickly and potentially redefine how care is delivered in the first-line setting. More broadly, this marks a turning point for Allogene 's platform strategy. The retirement of ALLO-647 is a strategic decision rooted in real-world experience. As the field evolves, our approach reflects where clinical practice is headed, not where it has been.
In the near term, it sharpens the path forward for the ALPHA3 trial. Looking ahead, it paves the way for our Dagger technology-enabled programs, which we believe define the future of allogeneic cell therapy: off-the-shelf, with reduced or no lymphodepletion, and built for real-world impact at scale. These changes strengthen ALPHA3 and sharpen Allogene Therapeutics' competitive edge. With safer regimens, outpatient potential, and real-world practicality, we are positioning Allogene to lead allogeneic CAR-T into everyday cancer care well beyond the academic setting. We will now open the call for questions.
Thank you. As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. The first question comes from Michael Yee with Jefferies . Your line is open.
Hey, David and team, thanks for the question. Maybe two questions. One is, as you've progressed since the last update, can you talk about how many folks have actually gotten the screening test? Therefore, what is the actual take rate versus the people who signed up? How does the MRD positivity number look early on? What % are actually getting the drug? What does a flow chart look like? The second question is, based on today's announcement, they'll now be randomized one to one, I guess. How does that change what you're looking for at the interim and the first half of 2026, which I think was based on 36 patients? Thank you.
Hey, Mike. Thanks for both questions. In terms of patient screening activity, as Zach has stated in the prepared remark, it has been extremely active. With that, I will ask Zach to provide more color.
Yeah, thanks, Mike and David. Mike, great question. I think what I heard was how many of the patients who are actually being approached for the study are actually undergoing tests. I would say that I don't have that exact number, but I would say it's the overwhelming majority, over 90%, of the patients who get invited to undergo the MRD screening test actually end up undergoing the test. As for the next layer, the number of MRD positives is consistent with what we had modeled, somewhere between one in four to one in six in that range, depending on the risk profile of the patient coming in. All of that is coming in as we have expected and as we have modeled in our current forecast. As David pointed out, the activity remains very, very high ever since we picked up at the beginning of this year.
As for the second question around the change in the number of patients that need to be enrolled, there will be a slight reduction in the number of patients overall that need to come into the study, because we are closing this FCA arm prior to it completing its full cohort. The analysis remains on track as first half of next year.
Thank you.
The next question comes from Tyler Van Buren with TD Cowen, and your line's open.
Hey, guys. Thanks very much for taking the questions. I have a couple for you as well. First, it'd be great just to have you elaborate on your confidence that this event is related to ALLO-647 and not Cema-Cel. It's logical given that FCA increases lymphodepletion versus FC, but is the lack of relation to Cema-Cel based primarily on the lack of adeno-infection or liver failure with FC and Cema-Cel, or are there other factors such as cell persistence of Cema-Cel versus the 647 antibody that you mentioned? The second question is, can you elaborate on what encouraging means when referring to the MRD conversion rate as part of the unplanned review?
I can jump in on that one. Thanks, Tyler. The first question around our confidence regarding the 647-based LB relatedness versus any role of Cema-Cel, I would say that our confidence on that is just about as high as it gets, just based on the intended lymphodepletion that is downstream of a CD52 monoclonal antibody like alemtuzumab or ALLO-647, and that is primarily directed at the T cells. In this patient, as in others, there was quite a profound suppression of the T cell count in response to that ALLO-647, and it is actually the low T cell count that gives rise to the risk of a disseminated adenoviral infection, not anything related to a B-cell directed cell therapy. Similarly, we had seen the frank disappearance of the Cema-Cel by the time that this event occurred, about seven weeks after the patient received the cells.
For all the folks who looked at this data, we were all pretty much unanimously in agreement that this was related to the lymphodepletion regimen. Sorry, Tyler, what was the second question?
Yeah, just elaborate on what encouraging means when referring to the MRD conversion rate.
Yeah. We're not going to get into numbers, and numbers of patients that we've looked at, but what I can say is that at this unplanned analysis, it looked like equipoise in terms of benefit being derived from this consolidation strategy, particularly as it related to the safety related to the FC only lymphodepletion arm, which those patients are doing very well from a safety perspective.
Thank you.
The next question will come from Salveen Richter with Goldman Sachs. Your line is open.
Good morning. Thanks for taking my question. Just two for me here. One is, given the study is now proceeding as a two-arm study and you're no longer enrolling in the enhanced LD arm, does that have any impact on study timing, like a futility in the early part of first half 2026, or when can we expect the primary EFS analysis and NBLA submission? Secondly, how many patients were enrolled in the enhanced LD arm and how many experienced viral infections or severe viral infections attributed to 647? Thank you.
Thanks, Salveen. I'll take this one. With respect to the first question, does this early closure of FCA lead to a change in the anticipated study milestone timing? The short answer to that question is no. We're still guiding towards an interim futility analysis in the FC arm, first half of next year. We will provide an update around the primary analysis and BLA submission when we get to that time point. No changes to guidance around the overall timing of the study milestones. I'm sorry, I didn't jot down the second question, Salveen. Would you mind repeating that one?
Sure. How many patients were enrolled in the enhanced arm, and how many experienced viral infections or severe viral infections that were attributed to 647?
Yeah. As previously, we won't be sharing specifics around enrollment, but what I can say is that we did an analysis across our safety database at the timing of this event. Looking at the CD19 experience, we had never seen a case of a severe adenoviral infection in ALLO-501 or ALLO-501A. This is the first one we did. There was one previous adenovirus infection, but it resolved without any lasting impact at all.
The next question will come from Biren Amin with Piper Sandler. Your line is open.
Yeah. Hi, guys. Thanks for taking my question. You mentioned that you would need fewer patients for the ALPHA3 trial. Can you maybe quantify what your new target enrollment numbers are? I think the prior target enrollment was around 240 patients all in for the trial. Second question, given the futility is coming up in the first half of 2026, can you maybe just talk about what you're hoping to see with that analysis? How many patients will you need to conduct the futility? What's the bar for futility? Is it basically comparable MRD conversion with Cema-Cel to the control arm to hit futility, or would the Cema-Cel arm have to be something worse than the control arm to hit futility? Thank you.
Thanks, Biren. With respect to the first question, how many fewer patients overall? We are not making any updates right now to the total number of patients that are required. As David and I both mentioned in the prepared remarks, the overall statistical design of the study is unchanged with the elimination of this FCA arm. It will just go forward as a one-to-one. The hypothesis testing is going to be performed on the same number of patients, 110 versus 110. There will, as I mentioned in a previous answer, be some, a handful fewer patients overall, but not such a large amount that would require us to update the overall target number of patients, as approximately 240. As far as the second question goes, we had previously disclosed that the futility analysis would be performed on 12 patients in each of the three arms.
That analysis will be performed now on just the two ongoing arms, FC and the observation arms. As for the bar for futility, we haven't specifically called that out, but suffice it to say we are going to be looking for an improvement in MRD clearance compared to the observation arm. Based on what we know from the MRD test performance characteristics, virtually none of the patients who are in the observation arm are expected to spontaneously clear their MRD, whereas we are, as pointed out, seeing an encouraging rate of MRD conversion in those patients who receive the FC lymphodepletion plus Cema-Cel.
Our next question will come from Brian Chang with JPMorgan . Your line is open.
Great. Thank you so much for taking our questions this morning. Maybe just first, just from your early look at the MRD conversion rates, what is the conversion delta that you're seeing between the FCA arm and the FC arm? We're curious on the efficacy that you might not be capturing when you're moving forward with ALLO-647. Second, was there any pausing in the enrollment of the study? If there was, how long was the pause and how could that potentially impact the pace of enrollment and also your timeline towards the trial completion of enrollment? Thank you.
Okay, thanks, Brian. The first question, what is the conversion delta between FC and FCA? I won't give you a specific number, and I'll even say that I think that we were quite pleased to see that those outcomes were highly similar. We do feel like we're in a good place. As we pointed out in our prepared remarks, we are confident about the potential for FC plus Cema-Cel to make a difference here. That's why we're carrying forward with agreement to the DSMB steering committee, etc. As far as the timing of enrollment, we've continued to screen MRD patients throughout this entire process, and the numbers continue to remain high. There is an adjustment to the protocol that is required, and that is underway now.
We expect this to have little to no impact in the timing of the analyses, because the amendment is so targeted just to allow us to cease enrollment in the FCA arm. Patients are continuing to undergo pre-screening during this period. If they turn up MRD positive, they will be able to come into the study at the point in the future. We don't expect an impact to the timing of the analyses.
Okay. Thank you.
The next question will come from Sami Corwin with William Blair. Your line is open.
Hey, there. Thanks for taking my questions. I was curious if the patient in question was treated at a community center or an academic center. Given the turnover at the FDA and CBER, I was wondering if you could elaborate a little bit more on your engagements with the FDA and how their responsiveness has been. Thank you.
Sami, let me give Zach a break and chime in here. In terms of the patient, that patient was treated in a community-based cancer center, essentially receiving the treatment more or less as an outpatient. We do not believe that had any impact on the outcome. I think this kind of rare event could have happened whether the patient was treated in the community or academic cancer centers. We don't see that as a major difference in the outcome. In terms of, I'm doing the same thing that Zach is doing. Can you just repeat the second question?
Yeah, given the volatility at the FDA and the recent turnovers at CBER, if you could just elaborate on your engagements there.
Yeah. I know that there has been a lot of comments on what's going on at the FDA, but I have to say our experience with the agency has been very productive and timely. We were quite eager to update the FDA about what's going on and our plan changes to the study, essentially dropping the FC arm. I would say the discussion occurred within days after we requested the meeting. This was relatively very quick and in a pretty collaborative and productive outcome.
The next question will come from Jack Allen with Baird . Your line is open.
All right. Thanks for taking the questions. I know a number have been asked already, but maybe I'll just piggyback on Sami's question around the discussions with the FDA. Are there any ongoing discussions with the FDA? Any outstanding matters as it relates to implementing the amendments necessary for the study to go forward here? I'm trying to quantify if there's any additional risk as it relates to regulatory in the near term.
Yeah. Always great question, Jack. I would say that at this point, there is relatively no outstanding issues with the agency. The feedback from the FDA has been very clear, and we are moving forward as Zach has outlined, with the randomizing patients to one-to-one.
Great. Thanks for the update.
The next question will come from Matthew Biegler with Oppenheimer . Your line is open.
Hey, guys. Sorry to hear about this. Has there been any collateral damage in terms of getting patients to commit to screening? Now, with this event, I understand it probably happened recently, but what are your, I guess, some of your early impressions in terms of recruitment or at least what you talk to your investigators about their ability to screen patients? Thanks.
Zach, do you want to take this question?
Sure. Thanks, Matt. I can say that we've seen no evidence thus far of any dip in MRD screening activity. Quite the contrary, we continue to see a lot of interest even post the disclosure to our investigators of this event. I think that there was broad agreement across our investigative pool that we took the right action here by addressing this emergent safety imbalance between the two arms and closing FCA. I think, actually, there's probably a chunk of our investigators who are excited that they won't have to worry about the 647 molecule anymore. That did add quite a bit of complexity on the lymphodepletion infusion days, very long days in the chair for the patients. Because of the enhanced lymphodepletion, it did put patients at somewhat higher risk of infectious complications.
Having that off the table in many cases, I think, is going to streamline the conversation that investigators are having with patients knowing that they're not going to be potentially randomized to the FCA arm.
Great. Thanks.
The next question will come from Asthika Goonewardene with Truist . Your line is open.
Hi. This is Karina for Azteca. Thanks for taking my question. Have you guys observed any differences in CAR-T expansion and persistence between the two lymphodepletion regimens? If you can, share information on that. My second question is, what infection protocols do you have in place for ALPHA3 study, and do you anticipate changing those going forward?
Karina, can you repeat the second question?
Yeah. Second question is, what infection protocols do you have in place for ALPHA3, and do you anticipate changes going forward?
Okay. Zach, do you want to take both questions?
Yep. I can take them both. Thanks, Karina. We won't talk about any additional biomarker data today, other than what we've already shared. You'll have to wait until a future update to look at the CAR-T expansion here. The second question around infectious protocols and prophylaxis. We actually have a very robust set of protocols of infection prophylaxis detailed within the study protocol and investigative brochure. This patient was compliant with all of those. It bears pointing out that adenovirus is a rare but known potential complication in cell therapy, predominantly in bone marrow transplantation setting where the conditioning regimens do rely on alemtuzumab. Even in those particular clinical settings where the risk is a little bit higher, there is consensus among the guideline setters in transplant to not prophylax for adenovirus and to just monitor for that infection.
This patient was being very well cared for by the physician team at the center where he was. This was an event that was really probably nothing could have been done whether he was cared for at that site or even at a major academic center. These rare events come on, and they come on quickly, and sometimes you just don't have time to react.
Thank you.
The next question will come from Samantha Semenkow with Citi. Your line is open.
Hi. Good morning. Thank you for taking the questions. I just have two questions following up on some others prior in the call. Just on the MRD conversion rates you're seeing for the FC arm, is that approaching what you're hoping to see in the futility analysis? I'm just trying to get a feel for how close that rate is to what would move the study forward, when we see the futility analysis in the first half. I just want to clarify that the unplanned analysis, does that impact the statistical power of any planned future analyses in the study? Thanks very much.
Hi, Samantha. Let me take both of those excellent questions. In terms of what we know about the MRD conversion, as we have said, this was an unplanned analysis, and it was very limited. Having said that, as Zach had indicated, we saw very little difference in the MRD conversion between FC and FCA. In terms of the futility boundary that we have pre-specified for the upcoming analysis next year, I would say that analysis, I think our focus will be more on the safety analysis. I think in terms of the MRD conversion rate, what we saw gives us a high level of confidence that the futility boundary will be met. I hope that answers the question.
Samantha asked the second question, David, around altering power, and I can quickly answer that one. There is no impact to the study powering based on this unplanned analysis.
Thank you, Zach.
The next question will come from Reni Benjamin with Citizens . Your line is open.
Hey, good morning, guys. Thanks for taking the questions. Maybe two for me. One, what kind of biomarkers outside of, you know, let's say CAR-T expansion and MRD conversions were evaluated? And then second, you know, with the closure of the FCA arm, which is the arm that I assumed at least would be the one moving forward, can you tell me maybe why or help me understand why the statistical powering assumptions for the interim and final analysis hasn't changed? Because I thought way back when, when we were running the ALPHA1 studies, I thought we had already answered this question that FCA was a better, deeper lymphodepleting regimen. Or am I not remembering correctly? Thanks.
Hi, Reni. Dave Chang here. Great questions. In terms of the important distinction that I think everybody has to sort of grasp is that the patient population of ALPHA3 trial, these are patients with minimal residual disease only. The target density, there's no bulky disease that the patient has. Also, patients were just coming out of the frontline R-CHOP regimen, so they don't have many B cells in the body. From that perspective, we had to rethink about what's really needed to eliminate the MRD-only disease. One of the hypotheses that we had set on early on is, yes, FCA is where we have the data coming from the relapse refractory setting where patients have bulky disease, but the patient population of ALPHA3 trial is a different patient population. We felt that there was a reasonable possibility that lighter lymphodepletion with FC may be sufficient.
So far, the biomarker data indicates that indeed is the case. With respect to the first question around what else have we looked at, in the unplanned analysis, MRD conversion was our primary focus, but things that were related to safety, suppression of T cells and the recovery of T cells after the treatment, all those were compared between the FC and FCA.
Perfect. Thank you.
The last question will come from Luca Izzi with RBC . Your line is open.
Oh, great. Thanks so much for taking our questions. This is Lisa on for Luca. Maybe just circling back on a prior question on the FDA, but asked a bit more directly. Is there any risk that the FDA could put this on a formal clinical hold or a clinical pause, or is that not being contemplated by the agency at this moment? Any color here would be much appreciated.
Yeah, I mean, I have a little bit of reluctance in trying to represent the FDA . In our conversation, that risk, I would say, I'm not concerned about that.
Got it. Thanks, David. Maybe just a follow-up. Did you consider using lower doses of anti-CD52 as the path forward?
Definitely. That was one of the earlier considerations, especially given that we are dealing with the MRD-only disease and also in the frontline setting where we consider the benefit-risk profile has to be a lot different than in the relapse refractory setting. That's what led to the decision of dropping the ALLO-647 relatively quickly and decisively. What's really helped us to make the decision was what we saw in the MRD conversion in patients who were treated with FC.
Maybe I can just add one final point to that. I think when we designed the study, all of us, myself included, I can certainly speak for myself here. I was hoping that FC would win out over FCA. It is an easier regimen to give, it has fewer lasting effects on the patient's immune system, and the hypothesis that we don't need the same degree of expansion and persistence to eradicate microscopic disease made me very hopeful that this would be the regimen that we would end up selecting. Of course, we would have loved to have this patient not experience this grade 5 event and get to the planned analysis as we had laid out. All the same, we are seeing encouraging conversion with the FC. We are very optimistic that this could in the end be the place that we had hoped to land from the outset.
Got it. Thanks so much for taking your questions.
Thank you. This does conclude our question and answer session. I would like to turn the conference back over to management for any additional comments.
Hey, everybody. Thank you again for your time and thoughtful questions. We appreciate your continued interest in Allogene and the ALPHA3 program. We look forward to keeping you updated as we advance this important trial and continue executing on our vision to transform access to CAR-T therapy. With that, thank you, everybody.
Thank you, ladies and gentlemen. Thank you for participating in today's conference. This does conclude the program, and you may now log off and disconnect.