Allogene Therapeutics (ALLO) Earnings Call zu Q2 2026: ALPHA3-Standorterweiterung und Pipeline-Updates

Wichtigste Erkenntnisse

• Allogene Therapeutics hat sein ursprüngliches Ziel, im Juli mehr als 80 klinische Prüfzentren für ALPHA3 zu aktivieren, erreicht und rechnet nun mit rund 100 aktiven Zentren bis Ende 2026.
• Die FDA hat Cema-Cel Ende Juli den RMAT- und Fast-Track-Status für die Erstlinienkonsolidierung gewährt. Das Management sieht diese Einstufungen als Bestätigung des ALPHA3-Programms sowie des ungedeckten medizinischen Bedarfs bei MRD-positiven Patienten mit großzelligem B-Zell-Lymphom.
• ALPHA3 zielt weiterhin auf 220 randomisierte Patienten ab. Trotz der schnelleren Aktivierung von Prüfzentren hielt das Management an seiner Erwartung bezüglich der Interimsanalyse zum ereignisfreien Überleben für Mitte 2027 fest.
• Bei Nierenzellkarzinomen mit hoher CD70-Expression erzielte ALLO-316 unter dem optimierten Schema eine bestätigte Gesamtansprechrate von 31 %. Bis zum Datenstichtag zeigte keiner der fünf bestätigten Responder ein Fortschreiten der Erkrankung, bei einer Nachbeobachtungszeit von acht Monaten bis über 18 Monate.
• Allogene geht davon aus, im vierten Quartal 2026 klinische und translationale Daten aus der RESOLUTION-Studie zu ALLO-329 vorzulegen, die mindestens die Dosiskohorten von 20 Millionen, 40 Millionen und 80 Millionen Zellen umfassen.

Geschäfts- und operative Entwicklung

ALPHA3 und Cema-Cel

In der ALPHA3-Studie wird Cema-Cel als Erstlinienkonsolidierung für Patienten untersucht, die nach der Erstbehandlung eines großzelligen B-Zell-Lymphoms weiterhin MRD-positiv sind. Die Strategie zielt darauf ab, Hochrisikopatienten vor einem klinischen Rückfall zu behandeln und gleichzeitig die Verabreichung sowohl an universitären Zentren als auch in der ambulanten Versorgung zu ermöglichen.

Bei der Futility-Interimsanalyse im April führte Cema-Cel bei der Mehrheit der Patienten zu einer raschen MRD-Eliminierung. Es gab keine behandlungsbedingten Krankenhausaufenthalte, und die meisten Patienten wurden vollständig ambulant behandelt und nachbeobachtet. Zudem wurde die Therapie auch in regionalen Praxen ohne vorherige CAR-T-Erfahrung erfolgreich verabreicht.

Infolge des gestiegenen Interesses von Prüfärzten erreichte Allogene das Ziel von mehr als 80 aktiven Zentren sechs Monate früher als geplant. Das Unternehmen rechnet nun bis Ende 2026 mit etwa 100 Zentren, von denen sich die meisten in den USA befinden, mit weiteren Standorten in Kanada, Australien und Südkorea.

Zudem hat Allogene eine Beobachtungskohorte MRD-negativer Patienten hinzugefügt. Laut Management wird diese Kohorte prospektive Erkenntnisse für die Ergebnisse randomisierter MRD-positiver Patienten liefern und dazu beitragen, den MRD-Test weiter zu charakterisieren.

ALLO-316

Die veröffentlichten Ergebnisse der TRAVERSE-Studie zeigten unter dem optimierten Schema eine bestätigte Gesamtansprechrate von 31 % für ALLO-316 bei Nierenzellkarzinomen mit hoher CD70-Expression. Zum Stichtag blieben alle fünf bestätigten Responder nach einer Einzeldosis progressionsfrei, bei einer Nachbeobachtungszeit von acht Monaten bis über 18 Monate.

Das Management betonte, dass der Datensatz nach wie vor klein ist und das Programm vor erheblichen Sicherheitsherausforderungen stand. Das Unternehmen erklärte, dass die Arbeiten zum Toxizitätsmanagement, der Austausch mit der FDA und die translationalen Erkenntnisse grundlegende Belege für die Dagger-Technologieplattform geliefert haben.

ALLO-329 und RESOLUTION

Die Rekrutierung für die RESOLUTION-Studie zu ALLO-329 bei Autoimmunerkrankungen ist über verschiedene Dosisstufen sowie sowohl unter Lymphodepletions- als auch Nicht-Lymphodepletionsstrategien vorangeschritten. ALLO-329 nutzt die Dagger-Technologie, die darauf ausgelegt ist, gezielt auf aktivierte T-Zellen des Wirts abzuzielen, die an der allogenen Abstoßung beteiligt sind.

Das für das vierte Quartal 2026 geplante Update wird Sicherheits-, Wirksamkeits- und translationale Ergebnisse umfassen. Das Management bestätigte, dass die Daten mindestens die Dosiskohorten von 20 Millionen, 40 Millionen und 80 Millionen Zellen abdecken werden, wobei laut Prüfplan auch höhere Dosierungen zulässig sind.

Ausblick des Managements

• Allogene rechnet damit, dass bis Ende 2026 rund 100 ALPHA3-Zentren aktiv sein werden.
• Das Ziel für die randomisierte Rekrutierung der ALPHA3-Studie bleibt bei 220 Patienten.
• Das Management rechnet weiterhin um Mitte 2027 mit der ALPHA3-Interimsanalyse zum EFS und hat den Zeitplan trotz der schnelleren Aktivierung von Prüfzentren nicht vorgezogen.
• Das Unternehmen rechnet damit, im vierten Quartal 2026 ein klinisches und translationales Update zu ALLO-329 vorzulegen.
• Allogene erwartet im Laufe des Jahres 2027 Gelegenheiten, Investoren über die Rekrutierung bei ALPHA3, regulatorische Fortschritte und potenziell auch Daten zu informieren, vorbehaltlich von Gesprächen mit der FDA und der Überwachung durch ein unabhängiges Data Monitoring Committee.

Risiken und Beobachtungspunkte

• Eine statistische Signifikanz bei der ALPHA3-Interimsanalyse zum EFS würde eine überwältigende Wirksamkeit erfordern, da das statistische Alpha zwischen der Interims- und der Hauptanalyse aufgeteilt wird.
• EFS-Ereignisse bleiben weiterhin verblindet, und das Antragspaket für den FDA-Status basierte in erster Linie auf MRD-Ergebnissen und einem umfassenden Sicherheitsdatensatz statt auf ausgereiften EFS-Ergebnissen.
• Die Nachweise für ALLO-316 basieren auf einer geringen Anzahl von Respondern, während das Programm auf erhebliche Sicherheitsprobleme gestoßen ist.
• RESOLUTION ist eine First-in-Human-Phase-1-Studie, die sich in erster Linie auf die Sicherheit konzentriert. Allogene hat noch keine detaillierten translationalen Ergebnisse zur Expansion oder Persistenz von ALLO-329 offengelegt.
• Das Management beobachtet weiterhin die Konkurrenz durch erstlinige autologe CAR-T-, bispezifische Therapien und In-vivo-CAR-T-Plattformen, obwohl es der Ansicht ist, dass ALPHA3 eine differenzierte Position in der Erstlinienkonsolidierung einnimmt.

Highlights der Analysten-Fragerunde

Könnte eine schnellere Aktivierung der ALPHA3-Zentren die Interimsanalyse zum EFS beschleunigen? Das Management hielt an der Erwartung für Mitte 2027 fest und erklärte, dass derzeit keine Anpassung bezüglich der Datenverfügbarkeit geplant sei.

Wie entwickelt sich die ALPHA3-Beteiligung zwischen universitären und regionalen Prüfzentren? Das Management beschrieb das Interesse als stark und ausgewogen. Etwa ein Drittel der Patienten in der Futility-Interimsanalyse stammte aus regionalen Praxen, und das Unternehmen möchte diesen Anteil beibehalten oder einer Parität näher kommen.

Könnte ALPHA3 mehr als 220 randomisierte Patienten rekrutieren? Laut Management bleibt 220 das Ziel. Zusätzliche Kohorten könnten in Betracht gezogen werden, wenn sich Gelegenheiten ergeben, aber eine erhebliche Überrekrutierung würde im Allgemeinen Daten erfordern, die ein akzeptables Nutzen-Risiko-Profil belegen.

Was bildete die Grundlage für den RMAT-Status? Allogene reichte die Ergebnisse der MRD-Interimsanalyse vom April, weitere MRD-Details sowie ein umfangreiches Sicherheitspaket ein. Das Management erklärte, die Einstufung zeige, dass die FDA das MRD-positive großzellige B-Zell-Lymphom als ungedeckten medizinischen Bedarf anerkenne und Potenzial für Cema-Cel sehe, diesen zu decken.

Was können Investoren vom ALLO-329-Update erwarten? Die Veröffentlichung im vierten Quartal 2026 wird voraussichtlich Sicherheits-, Wirksamkeits- und translationale Ergebnisse für mindestens drei Dosiskohorten sowie beide Lymphodepletionsstrategien enthalten.

Vollständiges Transkript des Earnings Calls

Vollständiges Transkript der Telefonkonferenz

Ausführungen des Managements

Operator

Hello. Thank you for standing by and welcome to Allogene Therapeutics second quarter 2026 conference call. [Operator Instructions] 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.

Christine Cassiano

Thank you, Operator, and welcome everyone to Allogene's conference call. After the market closed, Allogene issued a press release that provided a business update and financial results for the second quarter of 2026. This press release and today's webcast are available on our website. Following brief prepared remarks from Dr. Zachary Roberts, President and Chief Executive Officer, we will open the call for questions. Geoff Parker, Chief Financial Officer, will also join the Q&A. To help us conclude within 45 minutes, we ask that each analyst limit themselves to one question.

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, the potential treatment setting, and financial guidance, among other things. These forward-looking statements are based on current information, assumptions, and expectations that are subject to change. A description of potential risks can be found in our press release and latest SEC disclosure documents. You are cautioned not to place undue reliance on these forward-looking statements, and Allogene disclaims any obligation to update these statements.

I'm going to turn the call over to Zach.

Zachary Roberts

Thanks, Christine, and good afternoon, everyone. This is my first quarterly call as CEO, and it marks the beginning of a new chapter for Allogene, one made possible by the foundation David Chang helped build. David has been my mentor and one of the people who has most shaped how I think about cell therapy and drug development. More than that, he co-founded and built this company, led the field in the generation of clinical data in patients with relapsed cancer, and created the framework we needed to take Allogene into its next chapter.

When I joined Allogene, my mandate was clear. Challenge the conventional thinking about how allogeneic CAR-T should be developed. That meant starting with the patient and working backward. Understand what patients and their care teams need, then design products and clinical programs that meet those needs. That work led to a deliberate strategic shift announced in 2024, designing programs and products that leverages features of the allogeneic cell therapy into a clinical advantage. We focused on settings that demand the unique attributes of off-the-shelf CAR T, ready availability, consistent product quality that is independent of the patient's immune status, and crucially, the ability to treat patients locally. Allogeneic CAR T is not a stepping stone between autologous therapy and whatever may come next. It is a distinct platform capable of filling gaps existing modalities cannot and progress across ALPHA3, ALLO-316 and ALLO-329 is beginning to demonstrate those advantages in practice.

I will start with ALPHA3 because it is the clearest expression of this strategy. ALPHA3 arose from a simple premise. Can we identify patients at high risk of relapse after first-line treatment and intervene with CAR-T before the disease returns clinically? By treating earlier, the study aims to prevent relapse while avoiding much of the toxicity associated with standard second-line therapies, including autologous CAR-T. The trial is also designed to prove that we can overcome longstanding access barriers by enabling patients to receive CAR-T where they already received their first-line care in the community with the same doctors who gave them their first-line treatment.

Testing this required a more precise way to identify patients at high risk of relapse. Standard methods used at diagnosis, such as disease stage and IPI, lack sufficient specificity because many patients classified as high risk by those methods are still cured with R-CHOP. That new tool emerged just weeks before I joined Allogene. When I saw the Foresight now Natera CLARITY data presented at ASH 2022, the design of ALPHA3 came into focus.

When ALPHA3 began, MRD in large B-cell lymphoma was viewed largely as an academic research tool. We believed it could become far more a standard marker patient's prognosis and, if properly validated, a new treatment decision point. That view is gaining traction not only in LBCL but across oncology. In May, the FDA approved Tecentriq as adjuvant therapy for patients with bladder cancer who are in radiographic remission but remain MRD positive by circulating tumor DNA. The approval, based on the IMvigor011 study, is the first where patient selection was based solely on a ctDNA MRD test. IMvigor011 closely parallels ALPHA3's design and this approval, as well as a new Category 1 NCCN recommendation, signals a broader shift toward using MRD as a treatment decision trigger rather than waiting for clinical relapse.

Fast forward to our first look at data from the ALPHA3 trial in April, the interim futility analysis, which provided an important early test of ALPHA3's hypothesis. Cema-Cel drove rapid MRD clearance in a majority of patients and did so with no treatment-related hospitalizations. Most patients were treated and followed entirely in the outpatient setting. And importantly, Cema-Cel was successfully delivered in community practices with no prior CAR-T experience. Together, those findings support ALPHA3's potential to change the lymphoma landscape by offering CAR-T earlier with less logistical burden and greater access across more treatment settings.

At the end of July, the FDA granted both RMAT and Fast Track designations for Cema-Cel in first-line consolidation. These designations are based on two critical points. First, FDA acknowledges that MRD positivity at the end of first-line treatment is an unmet medical need. And second, Cema-Cel has the potential to meet that need. need. We interpret this action by FDA as validation for the ALPHA3 program. Additionally, RMAT creates an important opportunity for more frequent and focused engagement as we advance the trial. That engagement will be central to how we move forward.

Our objective is clear. Execute the study well, protect its integrity, and work with the FDA toward the most efficient development and regulatory path. As enrollment continues, we expect opportunities in 2027 to update investors on the program, including enrollment progress and potential data such as the planned interim EFS analysis. The timing and scope of these updates will of course be guided by our regulatory discussions and the independent data monitoring committee. In the meantime, we will communicate meaningful operational and regulatory progress.

Today we are proud to provide one such operational update. We entered the year with a goal of activating over 80 clinical sites by year end. With strong execution by the team and increased investigator interest following the interim futility analysis, we reached that goal in July. New academic and community-based investigators have asked to join the trial, citing enthusiasm for the initial MRD clearance data and safety profile and growing momentum of MRD testing in lymphoma. As a result, we now expect to have approximately 100 sites active by year end with the significant majority in the United States and additional sites in Canada, Australia, and South Korea. This expansion reflects growing investigator conviction in MRD and the ALPHA3 strategy, supports enrollment momentum, and gives more sites hands-on experience with Cema-Cel's ease of use ahead of a potential commercial launch.

Turning to ALLO-316, the publication of the TRAVERSE results in the Journal of Clinical Oncology was an important milestone for the program and the Dagger platform. Solid tumors have been CAR T's hardest test. In patients with CD70 high renal cell carcinoma, ALLO-316 produced a 31% confirmed overall response rate the optimized regimen. At the data cutoff, none of the five confirmed responders had experienced disease progression, with follow-up ranging from eight months to more than 18 months after a single dose of ALLO-316. The data set is small, and the program has faced real safety challenges. We've been direct about both. But consistently, confirmed responses with this degree of durability in a solid tumor are notable. Just as important, the translational work gives us a much clearer view of the underlying biology of these responses using CAR T-cell expansion, persistence, tumor infiltration, and the contribution of Dagger.

TRAVERSE also demonstrates how we operate. There were moments when the conventional decision would have been to stop development of ALLO-316. When toxicity emerged, our team brought in outside experts, engaged with the FDA, developed the management algorithm and continued learning. That work gave us a pathway to manage the most serious events while advancing understanding of an increasingly recognized immunotherapy toxicity and allowed us to generate the foundational clinical evidence for our Dagger technology pipeline. We are still far from declaring victory in solid tumors, but these results provide encouragement to keep pushing. They move the field forward and reinforce the principle that is central to allergy. When the biology is sound, we stay focused, learn from the data, and continue advancing the science.

That same focus on thoughtful program design brings me to ALLO-329 and the RESOLUTION trial in autoimmune disease, where the core message is execution. Enrollment has moved quickly across cohorts, dose levels, and lymphodepletion strategies, even in a highly competitive field. We believe that momentum reflects a program designed with patients as the focus rather than one that asks them to adapt to the technology.

ALLO-329 was designed with Dagger from the outset. Rather than designing another CAR-T product that requires chemotherapy-based lymphodepletion to work, the product is designed to function better when confronted by the biology of allo rejection by targeting the activated host T cells that contribute to it. Our objective is to both identify the optimal dose regimen for ALLO-329 and to understand how its cell dose, lymphodepletion, and Dagger work together. Strong enrollment and execution are keeping us on track to report a clinical and translational update by year end.

Across all three programs, the through line is clear. We embrace the features of allogeneic CAR-T as unique strengths and have designed programs to allow us to meet the demands of patients when and where they arise. Over the next 12 months, we expect the value of that work to become increasingly visible, beginning with an ALLO-329 update by year-end and opportunities to update investors on ALPHA3 throughout 2027. Those milestones will help define our progress, but the standard we are working toward is simpler. Innovation only matters if patients can actually access it.

We'll now open the call for questions.

Operator

[Operator Instructions] Our first question comes from Michael Yee of UBS.

Fragen und Antworten

Unknown Analyst

Hey, good afternoon, guys. This is Matt on for Mike. Thank you so much for taking your questions. I wanted to add, I saw you guys added an observational cohort to the ALPHA3 study, and I just wanted to ask about kind of the design of this cohort, maybe what the goal of it is, and kind of the questions you're helping to answer. It looks like it's an MRD negative patient. So just to kind of expand on kind of what the goals are. I'm wondering how we could just show what that observational cohort might be.

Zachary Roberts

Thank you so much. Matt, thanks for the question. So it's pretty straightforward. We added this cohort to help provide context for the overall results of ALPHA3 looking at the MRD-positive patients. Of course, those are the ones that we randomized now into ALPHA3, so having a paired MRD-negative cohort using essentially the same patient population as this is coming into ALPHA3 itself, will give that ability to compare outcomes in the observational cohort of the MRD positive patients as ALPHA3 with the MRD negative patients as well. So really it will give us the ability to further characterize the test itself in a prospective manner.

Operator

Our next question comes from Tyler Van Buren of TD Cowen.

Tyler Van Buren

Congratulations on your first call as CEO, Zach, and I appreciate the efficient prepared remarks. I guess given the acceleration of site activation by six months, is it possible that the interim EFS analysis could occur earlier than the guided mid-2027 timeline?

Zachary Roberts

Thanks for the question, Tyler, and thanks for the congratulations. It's a thrill to be CEO and it's an honor. So getting to your question, so we are currently maintaining guidance that the EFS should occur at roughly the same time as previously guided. We are just moving to try to accelerate the enrollment of the study and of course working very hard to bring on as many sites for the reasons stated in the prepared remarks. But at this time we're not making any adjustments to the expectation of data availability.

Operator

Our next question comes from Salveen Richter of Goldman Sachs.

Unknown Analyst

Hey, this is Mark on for Salveen. Thanks so much for taking our question and congrats on the progress. It was good to see the enrollment for ALPHA3 post the interim data. Could you give us a breakdown of enrollment cadence across academic versus community sites? Is the expectation still that it's going to be 1/3 community and 2/3 academic and what feedback are you hearing from the community physicians?

Zachary Roberts

Without getting too specific here, I would say that the interest continues to be very high and growing in both the academic corners as well as the community corners. I would say that, that the surge of interest that we did see after the interim data really was pretty balanced between the two. We had some pretty big names centers reach out to try to join. And then we've got quite a number of community practices that also ask to join.

So as far as how the patients break down in terms of where they come from, we actually have, I don't know if we've stated previously that it's about a third is expected. That's what we did see in the interim futility analysis. analysis, which was a very great outcome for us. I think that if we can maintain that or even bring it closer to parity in the final analysis, that would be something that we would be interested in doing. And that really does, I think, capture the last part of your question, which I believe was around what we're hearing from the various docs about the program.

I think everything that we heard early on when we launched the study and even before that when we were just talking about it with sites is that the community practices view this as really the best and first true opportunity to access CAR-T for their patient populations. And the academicians, on the other hand, you know, are very excited about, you know, cutting edge technologies, serving their patients in ways that improve the benefit-risk profile, ideally preventing relapse, which everybody universally agrees is a bad outcome.

So, across the board, we continue to hear very strong conviction that this strategy is excellent for patients, and then from the community practices specifically, enthusiasm around gaining access to CAR T, which has been out of their reach from the beginning.

Operator

Our next question comes from Samantha Semenkow of Citi.

Samantha Semenkow

Zach, let me add my congratulations on your first call as CEO. So just another one on ALPHA3. As we look forward to the interim EFS analysis mid-next year. Just wondering how we should think about that analysis in terms of the potential for overwhelming benefit to be demonstrated. If the interim MRD assessment that we saw is repeatable for with more patients. How likely is that to translate into a stat-sig benefit on EFS at the interim analysis? Thank you.

Zachary Roberts

Thanks, Samantha, and it's a great question. So, as we went into some detail when we released the data in April, the strong MRD clearance data that we observed we did think was quite positive and gave us some very positive views on the potential outcome of the study, either at the interim EFS or at the primary analysis. We also detailed that because of the way that we've allocated the alpha between those two EFS analyses, that it would require overwhelming efficacy to achieve statistical significance at the midway point there at the EFS, the interim EFS analysis.

You know, we can't really go into further detail around, you know, whether about how we're thinking about the likelihood of that statistical significance, except I will reiterate that prior studies such as the, the TRANSFORM study of Breyanzi illustrated that a 24% MRD clearance differential between the CAR T and the transplant arm translated into a greater than 60% improvement in the EFS between those two arms. So a very, very positive outcome there on a comparatively lesser differential in the MRD clearance rate.

So we remain very excited about the potential for a positive outcome here, but going into any further detail around how that might play out at the EFS analysis that is currently planned for middle of next year. I don't want to get too far ahead of myself on that one.

Operator

Thank you. And our next question comes from Matt Phipps of William Blair.

Unknown Analyst

Hey team, this is Josh on for Matt. Thanks for taking my question and congrats on such a good quarter. So I had a question on the RESOLUTION readout as it approaches. We were wondering what kind of data and the level of granularity that we should expect from the readout later this year.

Zachary Roberts

Thanks, Josh. So for the RESOLUTION trial, the data that is -- the data readout that we're currently planning for quarter 4 of this year, we expect to share clinical and translational data. I'll reiterate what was contained in the prepared remarks that we continue to be very pleased with the way enrollment is going. At the last call last quarter, we announced that we had treated nine patients in both the LD and non-LD containing arms. We have continued to see very robust demands to put patients into the study, so we should have a nice number of patients by the time we share that data in quarter 4, and then that will feature, of course, safety and efficacy outcomes as well as the translational findings.

Operator

Thank you. And our next question comes from Cha Cha Yang of Jefferies.

Cha Cha Yang

This is Cha Cha on for Roger. Congrats on the quarter as well. Just a question on the 329 trial with the data coming in fourth quarter. Just wondering if your guidance has changed in terms of the dose groups that you're going to announce. Are we still expecting the 20 million, 40 million and 80 million doses or is there any change?

Zachary Roberts

Thank you, Cha Cha. So those are indeed the first three dose levels or the first two dose levels. We also will be dosing patients with 80 million. And this, you know, there are additional doses above that are contemplated within the protocol. So as far as we get in that dose escalation, that will be the day. data that we share, but at least those three dose cohorts, 20 million, 40 million and 80 million, will be included.

Operator

Our next question comes from Jack Allen of Baird. Your line is open.

Jack Allen

Congrats on the progress over the quarter. I want to extend my congratulations to Zach on the new role. Really great to see you on the quarterly call here. My question is around the RMAT and Fast Track designations that you were able to secure over the course of the quarter. My understanding is that for RMAT specifically, there's a need to share clinical data when available with the FDA, and I'm just curious if you could provide any more context around what data was shared with the FDA. Was it really the April MRD data? Or were there additional clinical data that were shared with the FDA? And then also kind of in the same vein, what aspects of the data set were most intriguing from the FDA's perspective? Was it the efficacy? Was it the safety? Or was it a combination of the two? Any context you can provide would be very helpful.

Zachary Roberts

Thanks, Jack. Yes, we were thrilled to receive those designations. RMAT, as you point out, is it does in fact require clinical data. It's very similar to breakthrough therapy designation. And so the clinical data that we provided was derived from that interim analysis that we shared back in April. And of course, what we share with regulators, generally speaking, is quite a bit more extensive than what is shared publicly outside of the company. And so this was a complete briefing package that went into all the information. available detail that we had. Again, EFS at the time, the actual events were blinded and they remained blinded to us. So this was really focused on the MRD results, but additional detail around the MRD was provided to the FDA and of course, an exhausted safety package also.

In the FDA's decision, to award RMAT or not, they generally don't go into details about which aspect of the package was most enticing to them or most influential in their decision, but just generally that number one, that the disease under study, in our case MRD-positive large B-cell lymphoma represents an unmet medical need, which I really want to highlight as a pretty important thing for them to have pointed out, that this trial and this data set was even eligible for RMAT designation was predicated on that very fact, that MRD positivity is an unmet need. And then critically, of course, that MRD... Based on the data that they reviewed, Cema-Cel has the potential to meet that unmet medical need. So for those reasons, they decided to give us RMAT, but any further granularity, they did not provide.

Operator

And our next question comes from John Newman of Canaccord, who line is open.

John Newman

Congrats on the excellent progress. The question is, given the very impressive pace of enrollment for ALPHA3 and the increased target of enrollment sites to 100 by the end of the year. Are you open to the possibility of enrolling additional patients beyond the current target?

Zachary Roberts

Thanks, John. The short answer is we are going to try to find as many ways that we can in the context of an ongoing study to offer enrollment to patients who meet the eligibility criteria for ALPHA3. Within the confines of ALPHA3 as written, the target is the target, 220 patients randomized into the two arms and generally speaking you don't want to go much above that until data is available to suggest a benefit-risk ratio that is permissive of over-enrollment. However, if additional opportunities along the way present themselves to add cohorts or explore other nuances within this broader field. those things will be considered in due time. But as the time sits right now, our target is 220.

Operator

Our next question comes from Luca Issi of RBCCM.

Unknown Analyst

Adding our congrats to Zach and team on successful transition This is Cassie for Luca. Quick question on the 329. As Zach, you mentioned that dosing started for the lymphodepletion arm. Are you hearing any early anecdotes for CAR T expansion or persistence in patients treated with cyclophosphamide? And what positive signs are you looking for here at the 4Q update for this specific arm? Should we be thinking non-inferior or any specific benchmark. Any color, they're much appreciated.

Zachary Roberts

Thanks, Cassie. So, you know, we were, as all phase one, first in human studies are, they are primarily a safety trial. So this is why we started a low dose and go up, and really we're monitoring most closely the safety outcomes and then making decisions about whether the dose escalate, dose expand. at additional cohorts, what have you.

So we are collecting all of the safety information and we meet as a team with outside advisors prior to dose escalation. So that is the most important and comprehensive data package that we review in real time. We obviously are in close contact with the investigators around the efficacy and so, you know, as in previous statements, we've talked about encouraging signs of activity in that program and so, you know, I'll reiterate that now here is that we continue to have very robust interest and demand from investigators and patients to come in. on what we're seeing so far.

As far as the translational data goes, those data are developed sort of in parallel and typically in batches. But so we do not, you know, we're not in a position to comment on the translational findings here today, just that we will be including those findings in the upcoming fourth quarter data release.

Operator

Our next question comes from Reni Benjamin of Citizens.

Reni Benjamin

Zach, congratulations on the new role. I guess I jumped in late. I hope this hasn't already been asked, but I'm interested in the competitive landscape as it continues to evolve and how you guys are kind of thinking about things and managing it, in particular, you know, not just the frontline study for autology CAR-T's that are being evaluated but also the recent Legend in vivo CAR-T data. I would love to kind of get your thoughts as to how you manage these things.

Zachary Roberts

Thanks, Reni, for the question and for the congrats. So, great question. Thanks for asking it. It had not been asked prior to you joining, so good opportunity for me to dive in a little bit on that. So, obviously, we monitor the competitive landscape across our portfolio very, very carefully. And one of the things that we've enjoyed and continue to enjoy, I believe, is a pretty well protected place within this first line consolidation for ALPHA3. Nobody else has entered this space explicitly in that way yet. And the upfront, the first line studies that are ongoing, you mentioned CAR-T, but of course there's other specific pivotal studies as well.

You know, we've looked at this very carefully both through conversations with PIs and investigators that are involved in the studies and those that are not. And then we've also performed some fairly extensive blinded market research. And our conclusion from that, those ongoing frontline studies is that they'll actually have a fairly minimal impact on the overall rate of MRD positivity in the immediate post-frontline setting. And that's primarily because both the CAR T cells and the bispecifics tend to carry a fairly significant toxicity profile. They're a bit cumbersome. some for patients and with some of them needing step-up dosing and even prospective hospitalization just to administer the therapy.

So this is largely, in my view and in the view of the respondents to our study, will probably be reserved for select patients and select centers. So by and large, being that most patients, 80% or more, are treated in the community practices, the MRD rate is likely to stay pretty much where it is, primarily driven by outcomes following R-CHOP and R-Pola-CHP.

With respect to the question around in vivo, And my view on this, and I think this has been validated through several conversations I've had, is that obviously an extremely exciting platform for the field and for patients, but likely I believe it will primarily suffice to replace autologous CAR T in the relapsed refractory setting, again pointing primarily to the toxicity profile, at least in the early days here, unless that gets markedly better, most community oncologists are not going to be enthusiastic about administering a large dose of active viral particles into patients during a busy clinic afternoon.

So, it feels like this is an opportunity for really, an off the shelf CAR T being available to community oncologists. They can give it in their infusion clinics over five minutes and the patients can be reasonably assured to go home without having much toxicity. At least that's the intention of ALPHA3. So clearly a lot of activity both upstream from us as well as downstream from us with the in vivo, but we think we're pretty well protected here right in the middle.

Operator

Thank you. That concludes our question-and-answer session. 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.