Allogene Therapeutics Q1 2025 Earnings Call Transcript

Quartr
Provided by Quartr
May 13, 2025

There are 12 speakers on the call.

Operator

Hello. Thank you for standing by, and welcome to Allogene Therapeutics first quarter twenty twenty five conference call. After the speakers' presentation, there will be a question and answer session. As a reminder, to ask a question, you will need to press 1 1 on your telephone and wait for your name to be announced. Please be aware that today's conference is being recorded.

Operator

I would now like to turn the call over to Christine Cassiano, Chief Corporate Affairs and Brand Strategy Officer. Ms. Cassiano, please go ahead.

Speaker 1

Thank you, operator, and thanks to all of you for joining this call. After the market closed, Allogene issued a press release that provided a business update and financial results for the first quarter of twenty twenty five. This press release and today's webcast are available on our website. Following our prepared remarks, we will host a Q and 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 1

I am joined today by Doctor. David Chang, President and Chief Executive Officer Doctor. Zachary Roberts, Executive Vice President of Research and Development and Chief Medical Officer and Jeff Parker, Chief Financial Officer. During today's call, we will be making certain forward looking statements. These may include statements regarding the success and timing of our ongoing and planned clinical trials, data presentations, regulatory filings, future research and development efforts, manufacturing capabilities, the safety and efficacy of our product candidates, commercial market forecasts and financial guidance, among other things.

Speaker 1

These forward looking statements are based on current information, assumptions and expectations that are subject to change. A description of these potential risks can be found in our press release and latest SEC disclosure documents. You are cautioned not to place undue reliance on these forward looking statements, and Allogene disclaims any obligation to update these statements. I'll now turn the call over to David.

Speaker 2

Thank you, Christine, and welcome, everyone. Today, we come together at a defining moment for Allogene, a moment that potentially validates the bold forward looking strategy we launched in January 2024. At the time, we committed to doing what no CAR T had done before. That strategy wasn't about being autologous or allogeneic. It was about breaking boundaries.

Speaker 2

One year later, that decision looks not just bold, but present. I believe we have built something extraordinary, especially for a small biotechnology company in the current market environment. We have a trio of highly differentiated clinical assets, each with a potential to be transformative. Combined, they demonstrate that allogene is potentially changing the trajectory of cell therapy. At the center of that vision is ALPHA3, a pivotal first line consolidation trial with Semacell, which we believe will transform care in large B cell lymphoma and open the door for community cancer centers.

Speaker 2

The use of MRD paired with first line treatment consolidation is a radical departure from traditional approaches, and it's gaining powerful traction. What once seemed ambitious is now being embraced across nearly 50 activated US sites. Investigators recognize that ALPHA-three is not just another CAR T study. It seeks to redefine how to identify and when we treat high risk patients. That recognition is reflected in the collaboration we are seeing across sites, many of which are proactively developing and sharing patient identification strategies.

Speaker 2

Launching this groundbreaking trial has come with important lessons. We've had to adapt quickly to unexpected hurdles from site level staffing shortages to educating patients who believe their treatment journey was complete when they received the news of a clean PET CT scan. These insights are now guiding smarter enrollment tactics, more effective communication with patients and more precise forecasting. The result has been tangible. To date, over two fifty patients have consented for MRD screening with nearly half in the last three months.

Speaker 2

With improved site engagement and more patients introduced to the trial earlier, we are seeing the early returns of a system that is working. In light of these operational dynamics, we have shifted the lymphodepletion regimen selection and futility analysis milestone into the first half of twenty twenty six. While that's two quarters later than planned, it reflects a strategic decision to prioritize precision, insight, and the stronger foundation for a future commercial launch. During this time, we are also actively evaluating what data will be most meaningful to share at the time of the lymphodepletion selection and futility analysis in response to feedback from stakeholders. ALLO-three sixteen in the TRABERSE trial continues to break new ground, showing signs of efficacy in patients with heavily pretreated advanced renal cell carcinoma.

Speaker 2

These patients are highly refractory to treatment and often only have months to live. For these patients, ALLO-three sixteen may offer something they never thought possible, hope. With our CD70 targeted dagger technology, ALLO-three sixteen is providing a clear demonstration of potential that CAR T holds in solid tumors, something the field long viewed as aspirational. Zach will comment further on ALLO-three 16 and our upcoming oral presentation at ASCO on June 1. In the RESOLUTION trial launching mid-twenty twenty five, ALLO-three 29 is poised to change how we treat autoimmune disease.

Speaker 2

This dual targeted allogeneic CAR T product offers the potential to eliminate lymphodepletion entirely, which is a major hurdle to broader CAR T adoption. This is not a variation of what others are doing. It's a completely new strategy designed to intercept disease at its root in conditions like lupus nephritis and systemic sclerosis. As we move our trials forward, we are keenly aware of the macroeconomic environment. Preserving our cash runway remains a top priority.

Speaker 2

With a refined operational strategy and efficiency driven cost realignment, we have extended our cash runway into the second half of twenty twenty seven. This gives us the ability to weather market headwinds as we drive ahead to our most promising clinical inflection points. The field of cell therapy is evolving. The autologous versus allogeneic debate is giving way to a bigger question. How broadly can CAR T be applied?

Speaker 2

At Allogene, we are answering that question with action. Our strategy set in motion in January 2024 was never about following existing models. It was about doing what had never been done before and importantly, making CAR T more accessible by harnessing the unique advantages only an allogeneic approach can deliver. With ALPHA-three, ALLO-three 16, and ALLO-three 29, We believe we are proving that CAR T is not just about cell type or delivery mechanism. It's about clinical ambition, real world insights, and building a scalable future for patients who need more than incremental change.

Speaker 2

Finally, while it is unusual for me to use our quarterly call to address some of the macro issues impacting our industry, it is more important than ever to take a moment to do so. Like many in the industry, we are serving the evolving landscape at FDA and assessing potential implications. Grounded in our continued confidence in the agency's mission, scientific integrity, and dedication to patient centered progress. The selection of Doctor. Vinay Prasad, a well known voice on drug development reform has sparked a range of reactions.

Speaker 2

But in moments like this, it is important to take a breath and recognize the broader context. While Doctor. Prasad has been a provocative voice at times, he has also long advocated for rigor, transparency, and patient centered outcomes, value we share. It is also worth remembering that the clinical review of oncology products, including those under CBER continues to rest with the oncology center of excellence. That structural continuity should offer some reassurance that therapeutic evaluation will remain grounded in science, precedence, and patient need.

Speaker 2

Rather than speculate, our approach will be to engage, educate, and collaborate. If this marks a new chapter in regulatory thinking, we intend to be a constructive part of that dialogue. Ultimately, we believe that strong science and meaningful clinical benefit will continue to carry the day and we remain confident in the value of our programs to patients who needs better options. On all front, we believe Allogene has a responsibility, not just to participate in the future of medicine, but to lead, to help shape and define it. I would like to now hand the call over to Zach.

Speaker 3

Thank you, David. As David shared, this is a pivotal time for allergy, not just in terms of vision, but execution. The progress we are making across all three of our clinical stage programs is the result of years of scientific rigor, operational learning, and close partnership with the clinical community. Let's begin with alpha-three, where the enthusiasm we're seeing from nearly 50 activated sites across The US is not only sustained, it is growing here and internationally. This trial represents a true paradigm shift.

Speaker 3

Sites, including those new to CAR T, have embraced this concept, and we're seeing a level of collaboration that is rare in oncology trials. But as first movers, we've also encountered realities that no modeling could fully anticipate. Site level operational constraints, including staffing shortages and administrative hurdles, led to slower than expected transitions from site activation to patient screening. Bifurcation of care between frontline lymphoma doctors and second line cell therapy providers, even sometimes within institutions, required us to build bridges that had never been built before. Well worn monologues given to patients at the time of their diagnosis honed over decades telling them that a clean PET scan at the end of therapy means they are cured needed to be updated to reflect the increased power of prognosis coming from MRD results.

Speaker 3

We've responded by doubling down on engagement, embedding trial education earlier in the patient journey, and supporting sites in identifying patients who are most likely to be MRD positive after frontline therapy. Those investments are working. As David noted, with improved site and patient engagement and education, we have now consented over two fifty patients for MRD testing since the start of the trial. With robust month over month improvement in the screening rate, especially since the earliest sites to activate began hitting their stride early in 2025. Nearly half of these patients have been consented in the last three months, and many of them are still undergoing frontline treatment.

Speaker 3

Furthermore, many sites are sharing with one another, an encouraging sign that this trial is building momentum. The central value proposition of this trial that a patient's MRD status, positive or negative, is a critically valuable piece of information and that a single dose of an off the shelf CAR T can eradicate residual disease to cure patients of their lymphoma has only gained traction with doctors and patients. We are looking to further feed that momentum and embrace the enthusiasm we've experienced from potential investigators outside The US with international expansion of alpha-three. The first ex US sites we will launch are in Canada, which are on track to activate in the next several weeks. Turning to ALLO-three 16.

Speaker 3

This program continues to challenge expectations for CAR T in solid tumors. We're excited that the updated results from the Phase 1b expansion cohort will be featured at an oral presentation at ASCO on June 1. This data will be presented in the main kidney and bladder cancer session at ASCO, alongside updates of pivotal data sets and cutting edge combination trials presented by respected leaders in RCC. That alone signals how important this data could be to the field. What makes ALLO-three sixteen so compelling is that it is one of a very small handful of CAR T therapies and the first allogeneic to demonstrate meaningful activity in solid tumors with just a single infusion.

Speaker 3

To have achieved this, especially with a standard lymphodepletion regimen, puts ALLO-three sixteen in a class of its own. That ALLO-three sixteen achieved this in a patient population as sick and heavily pretreated as these Phase Ib patients, which may be some of the most treatment refractory patients ever studied in RCC, is truly groundbreaking. Individuals with metastatic renal cell carcinoma who have failed every approved therapy face a prognosis measured in mere months. For them, ALLO-three sixteen may offer not just treatment, but a potential lifeline. In our data cut presented at SITC last November, eight patients were treated in the Phase 1b expansion cohort.

Speaker 3

In the six of these heavily pretreated patients whose tumors expressed high levels of CD70, we observed a fifty percent best overall response rate and a thirty three percent confirmed response rate, results that we believe underscore the promising potential of this therapy. The upcoming ASCO presentation will build on those results with additional patients treated and longer term follow ups of the results presented at SITC. Key translational findings, including the role of our CD70 targeted dagger technology in promoting CAR T cell expansion and persistence, reveal a mechanistic basis for the clinical results and give us confidence that ALLO-three sixteen could be a blueprint for CAR T in solid tumors more broadly. We've completed enrollment in the Phase 1b expansion and are actively evaluating strategic options for the path forward, including potential partnerships. We look forward to sharing this data with the community next month.

Speaker 3

Finally, I want to briefly touch on ALLO-three twenty nine and our progress in autoimmune disease. This is a new frontier for cell therapy, and ALLO-three twenty nine is engineered for it. The Phase I RESOLUTION trial launching midyear is a first of its kind basket study across multiple rheumatologic indications, and it features a truly innovative design, including one arm without any lymphodepletion at all, thanks to the inherent advantages of our DAGGER technology as demonstrated by ALLO-three 16. We expect proof of concept data first half twenty twenty six as we apply our experience with alpha-three and the potential for delays to patient screening activity following site activation. But the most important takeaway is our continued to believe that this trial could unlock significant potential across a broad spectrum of immune mediated diseases.

Speaker 3

In summary, the Allogene story today isn't just about bold ideas. It's about a growing body of evidence that allogeneic CAR T is no longer a theoretical promise, but a transformational reality on the verge of reshaping the field. Each of our programs is moving forward with increasing clarity and confidence. And I believe the data we are generating will shape how this field evolves in hematologic malignancies and solid tumors and an autoimmune disease. With that, I'll hand the call over to Jeff.

Speaker 4

Thank you, Zach. We've covered a lot on today's call. And as David noted, we've taken deliberate steps to extend our cash runway into the second half of twenty twenty seven. As we evaluated where we would spend our capital, our number one priority was to provide the resources necessary to ensure we could advance our trials with urgency and purpose. These programs are not merely aspirational.

Speaker 4

We

Speaker 3

believe they are on

Speaker 4

the cusp of potentially delivering transformative outcomes for patients. That creates both a responsibility and an opportunity to our patients and to our shareholders to see them through. To that end, we are making targeted reductions in our current manufacturing operations to achieve key cost savings, while carefully maintaining our core capabilities to ensure the long term value of our strategic manufacturing assets. We are fortunate to have sufficient inventories of SEMICELL, ALLO-three twenty nine and ALLO-three sixteen to supply our ongoing ALPHA-three resolution and TRAVERSE trials, reflecting the inherent efficiencies of producing an allogeneic CAR T product, including the ability to manufacture product well in advance. As a result, we can implement these targeted cost savings initiatives without impacting trial conduct.

Speaker 4

We firmly believe that companies built on strong science and bold differentiated strategies are best positioned to navigate today's market challenges and emerge stronger on the other side. To that end, we will continue to exercise capital discipline, ensuring we remain well positioned to advance our programs with focus and strength all the way to the finish line. I will now review our most recent financial results. As of 03/31/2025, we had 335,500,000 in cash, cash equivalents and investments. Our research and development expenses for Q1 twenty twenty five were $50,200,000 including $5,000,000 in non cash stock based compensation expense.

Speaker 4

General and administrative expenses for Q1 twenty twenty five were $15,000,000 including $7,100,000 in non cash stock based compensation. Net loss for Q1 twenty twenty five was $59,700,000 or $0.28 per share, including $12,200,000 in non cash stock based compensation. Our updated guidance for 2025 is an expected cash burn of approximately $150,000,000 We expect full year 2025 GAAP operating expenses to be approximately $230,000,000 which includes an estimated non cash stock based compensation expense of approximately $45,000,000 This guidance excludes any impact from potential business development activities. We'll now open the call for questions.

Operator

Thank And as a reminder, to ask a question, you will need to press +1 01 on your telephone and wait for a name to be announced. To withdraw your question, please press +1 01 again. Please stand by while we compile the q and a roster. One moment for our first question. Our first question will come from the line of Michael Yee from Jefferies.

Operator

Your line is open.

Speaker 5

Thank you. Good afternoon. Obviously, our first question is on the understanding the progress of the enrollment of the first line study. And you had commented about some logistical issues in terms of operational handoff at the sites. Could you explain what the issue is and how you think that's resolved?

Speaker 5

And as part two of that same question, when you talk about two fifty people that have been consented to screening, that means they're consenting to be tested. That doesn't necessarily mean that they're actually going to get into the study. So is your timing of the interim based on a whole bunch of assumptions, including how many people would be positive and then actually have to enroll into the study? Thank you.

Speaker 2

Hey, Michael, thanks for your question. Let me take the first one and I'll ask Zach to answer your second question. In many ways, ALPHA-three study from the beginning, there were some puzzling findings. What we found was the excitement, enthusiasm that we are seeing from the investigator. As we have previously stated, that was far above any other experience that I have personally had in doing clinical studies.

Speaker 2

On the other hand, the actual delivery of the site, the enrollment and in a patient screening from the site, there was a lag that we just could not understand. But as the study evolves and that progresses, what we have found is this consistent about three to four month delay. And frequently this is all attributed to the fact that the site did not have personnel to cover another study. So this is the disconnect that we are trying to understand. And now we are enough into the study that we clearly understand what was going on.

Speaker 2

It was purely site related issues that as three to four months from the site activation. This is essentially getting all the paperwork completed to site actually beginning to screen. And this now we're getting to the point where we are actually seeing the patient being consented for screening and over past three to four months that has been very consistent and now meeting all the initial assumptions that we are making on the study. And I would also say that as we are looking into expanding study outside The U. S, the investigator enthusiasm for ARPA3 study is just as high as ever that I've seen.

Speaker 2

And this is one of the positive things. So what do I think? This is a definitely study that is doable. We just did not plan out and we did not predict that this added delay from the site activation to site actually beginning to deliver. So that is what's accounting for us to push out the timeline by approximately two quarters.

Speaker 3

And Mike, I'll add to that, that really speaking to what David just outlined, the fact that we've seen such a very nice pickup in the amount of patients that are signing up to undergo screening really since the beginning of the year, as we indicated in the press release. That really has been quite validating of observation that we are making that that was a little bit of a slow start, but the sites and the enthusiasm that they've had from the beginning is now translating directly into screening activity. As far as the question around the two fifty, you are correct. That doesn't mean that there are two fifty patients that are ready to undergo randomization. That is the number of patients that are consented to screen for the MRD test.

Speaker 3

Now of course, we need that number, those patients to undergo screening and then test positive for them to be randomized. So we think of this as a funnel and that is the top of the funnel. So we're seeing lots of terrific activity at the site level that will translate as it is currently translating into

Operator

enrollment. Thank you. Thank you. One moment for our next question. Our next question will come from the line of Tyler Van Buren from TD Cowen.

Operator

Your line is open.

Speaker 6

Hey, guys. Thanks very much for the questions. The first one related to ALPHA-three, of course. So are you seeing a significant difference in the occurrence of these site related factors at community versus the more academic sites? And what do you believe is the probability that we still get an interim EFS readout from alpha-three by the end of next year?

Speaker 6

And then the second one, just to follow-up on your Doctor. Prasad comments, given his appointment at CBER, been critical in MRD. It would be helpful if you could elaborate on why those don't necessarily apply to the ALPHA-three clinical trial program.

Speaker 2

Hey, Tyler, great questions. Let me take the second one since I made some comments about new director of the CBR in my prepared statement, and I'll ask Zach to cover the first question. My belief is always been that FDA values evidence based approach. I mean, that is by twenty plus years of experience, some are very contentious discussions that I have had with FDA. But at the end, what prevails is evidence based discussion and a meaningful clinical benefit that you can demonstrate.

Speaker 2

You know, the particular question of MRD that I have to say that in our study for alpha-three study, that doesn't really apply. MRD in ALPHA-three study is being used for patient identification, patients who are at high risk of having a disease recurrence after frontline treatment and we are selecting those patients. And this will be somewhat akin to using either clinical risk stratifications or any other things that people have been using all throughout drug development in oncology to identify high patient risks. When it comes to the clinical endpoint, we're using event free survival, which is the same clinical endpoint that had previously been used in the second line setting of autologous CAR T. So back to your question around MRD as a surrogate endpoint, that obviously there's a lot of discussions that are ongoing.

Speaker 2

And I do hope that in the future that there is enough evidence to elevate MRD as a surrogate endpoint even for non Hodgkin's lymphoma. But as I said, it is not directly relevant to, what we are doing. Another thing that I would say about the evidence based approach, Let's not forget that alpha-three study is not a single, study. This is a randomized control study, which is a gold standard of study design one can undertake when you're evaluating a new treatment or, unapproved products. So from that regard, how we identify the patients and how we are testing them in a randomized study and how we are using a clinical validated points.

Speaker 2

I think all these is really the core of evidence based approach that FDA has embraced over the years. And I do not have any concerns about the study design of ALPHA-three under the new leadership at CBER.

Speaker 3

And Tyler, I'll address the first question, which I think was about the startup times and the screening activity in community versus academic centers. I would say that there's not a clear delineation between the two. Generally speaking, it has taken quite a bit longer for all sites to come online than I think many of us have experienced in our prior lives. So I don't think that there is much of a difference between those two. But it is clear that once they get up and running, are screening patients very, very aggressively.

Speaker 2

And then let me just finish up your question about event free survival towards the year end of 2026. At this point, we intentionally remain silent beyond what we have said, which is communicating the lymphodepletion and futility analysis data in the first half. At that time, we will definitely have a lot more clarity on the data pace of the study and we plan to provide additional guidance and overall study together with lymphodepletion. And as we have said in the prepared statement, we are looking into ways to make the lymphodepletion selection announcement more meaningful. Previously, we have stayed away from potentially sharing any kind of data, but we are reviewing that decision and we will update you accordingly.

Speaker 6

Very interesting. Thank you.

Operator

Thank you. One moment for our next question. Our next question will come from the line of Byron Ahmed from Piper Sandler. Your line is open.

Speaker 7

Yeah, hi guys. Thanks for taking my questions. Just on the ALPHA-three, do you believe all sites have sufficient staffing currently compared to, I guess know, I guess when you first initiated the study? And then I guess a couple of other questions around the trial. What's the conversion rate from consent to randomization?

Speaker 7

And what's the average time that it takes a patient to go from consent to randomization? Thanks.

Speaker 3

Hey, Biren. So with respect to your first question, are sites adequately staffed? I would say generally, yes. I think part of what we saw was them having to get internal regulatory sign off and operational pieces in place, get the study staffed, and then critically understanding the workflow of how they're going to identify these patients and then get them consented and screened. So that took some doing.

Speaker 3

But in all cases, more or less, it is up and running very nicely now across the sites. Of course, the ones that are coming on most recently, they're going through that process now. But we now know all of the pitfalls and how to support them so that we're trying to shrink that three to four months down to as little time as possible in these more recently activated sites. As far as the other two questions around conversion rate and time from screening to randomization, I'm going to defer clear answers on those questions until we're at a point where we can share more data about the trial. We generally don't give that kind of granularity.

Speaker 3

But I'll say if David, if there's anything else you want to add to that.

Speaker 2

Yes. I mean, Biren, in terms of site staffing, yes, sites step up. But another thing that is helping us greatly is during the course of trying to troubleshoot what was going on. We have had multiple discussions with investigators and investigators themselves coming up with ideas about how to identify patients who could be eligible from the study. This entails looking at not just patients who are coming into the clinic, but looking at their own database, appointment books and others.

Speaker 2

And I would say that is also helping greatly. And these are the kind of the learnings that sites volunteer. This is works really well and you should really share with other clinical sites, which we have done exactly. Conversion rate, I mean, as Zach said, we're going to sort of defer providing that details. But in terms of timing, keep in mind when somebody consents to undergo MRD testing, that is any time during the twelve weeks of the frontline large B cell lymphoma treatment.

Speaker 2

So twelve weeks of eighteen weeks. Twelve to eighteen weeks of the frontline treatment. So we have to wait for them to complete and sometimes people consent when they're beginning, sometimes they consent more towards the end. So there is a little bit of variability. And once they undergo MRD testing, so far the metrics on MRD testing has been working out great.

Speaker 2

It still takes another two to four weeks after identifying MRD positive patients to get the logistic takes taken care of to randomize those patients. So these are the things that in retrospect we have not fully embedded into the timeline of the study, which is the reason that we are pushing out lymphodepletion selection timeline by two quarters.

Speaker 7

Perfect. Thank you.

Operator

Thank you. One moment for our next question. Our next question comes from the line of Brian Chang from JPMorgan. Your line is open.

Speaker 8

Hey, guys. Thanks for taking our questions today. Just two from us. It seems that you still have a bit of a gap to enroll the first thirty six patients. First is that, is the lack in screening that attributed to the three to four months of delay more concentrated in the community based sites?

Speaker 8

And then second, you related to the expansion to the international sites. How might that impact the ultimate patient mix and also powering of your initial assumptions? And more importantly, is there any regulatory implication in this expansion? Have you received the FDA feedback on this?

Speaker 3

Hey, Brian. This is Zach. So I think your first question is on the march towards 36 patients randomized and followed for MRD conversion. Are we seeing differences in the community versus academic? And the answer to that question is no.

Speaker 3

But let

Speaker 2

me pause to see, is

Speaker 3

that what you were asking, whether we're seeing a difference in activity there in a community versus academic?

Speaker 8

Yes, that's correct.

Speaker 3

Yeah. So no, we're actually seeing quite encouraging activity from both large academic practices, but also community practices. And again, including community practices with no prior CAR T experience. So all of the things that we found attractive about ALPHA3 are playing out very, very nicely in this study. As far as our expansion into the ex U.

Speaker 3

S. Territories, will that introduce heterogeneity into the patients? The short answer to that question is no. And the reason is quite simple. R CHOP is the global standard for frontline DLBCL treatment, full stop.

Speaker 3

Very few regions even have a second alternative like Pola R CHIP. So if anything, it will increase the homogeneity in terms of what that prior therapy is in those ex US territories.

Operator

All right. Thank you. One moment for our next question. Our next question will come from the line of Matthew Begler from Oppenheimer. Your line is open.

Speaker 5

Guys. Thanks for the question. I wanted to maybe shift things and ask about the INI strategy. David, it sounded like, at least from the prepared remarks, you're being pretty cautious on the burn. Obviously, know, INI is a big component of that burn.

Speaker 5

So my question is, would you guys be open to partnering that program away or are you still 100% committed to it? Or maybe the answer involves waiting for some early data first to make that decision? Thanks.

Speaker 2

On the different market environment, my answer would have been different. But in the current market situation, really protecting the cash runway is the key. So if there is any kind of reasonable deal to be had, we will we have indicated previously that we are very willing to partner and derisk the autoimmune programs, especially given that this is not our core therapeutic area of expertise. And in terms of pushing the timeline from the year end to the first half, I think this is just a little bit more providing a little more caution, but also it's factoring in the feedback that we've been getting from the investors. Previously, we were focused on just using the biomarker data as a proof of concept, But somewhat consistent feedback that we have gotten from the investigators.

Speaker 2

Yes, but you want to see a little bit more there. You got to have some clinical responses as well. So just to do both, having a little more cautious and little bit of buffer as well as giving the clinical team opportunity to include a clinical update on the patients who are treated. That's the reason that we are pushing out the timeline for the proof of concept data from '3 to '9 to the first half. I would just add, I mean, we are in the midst of site identification and activating the clinical trial sites for ALLO-three 29 study.

Speaker 2

And that process is going exceedingly well and we feel very optimistic as well as we are very enthusiastic about this program.

Speaker 5

Appreciate it.

Operator

One moment for our next question. Our next question will come from the line of Samantha Simcoe from Citi. Your line is open.

Speaker 1

Hi. Good afternoon. Thanks very much for taking the question. Just following up on ALLO-three 29, I'm wondering in the initial readout, what is the general size of the dataset that you think would be sufficient for you to be comfortable making the decision on which lymphodepletion regimen to move forward with? And just related to that, do you believe you'll see any of similar challenges in the resolution study as you are seeing in ALPHA-three as it comes to staffing issues?

Speaker 1

Thanks very much.

Speaker 2

Well, in terms of the second question, based on our experience, it will be foolish for us not to at least be paying a lot of attention to the site staffing issue, which we are doing as part of the site activation process. But based on our experience, it is a real issue, especially in autoimmune disease studies. Not only it's a site staffing issue, we have to bring together cell therapists as well as rheumatologists on the same room to be able to conduct the study. So there is added logistical challenges of doing the autoimmune studies with a CAR T. And in terms of the expected data, this is a dose escalation as well as testing two lymphodepletion regimen.

Speaker 2

In terms of the number of patients that we can reasonably treat, it will be a handful of patients because there is a wait period between first and subsequent patients at each dose level as well as wait time between escalating from one dose level to another. And your other question about are we going to make any lymphodepletion selection regimen? Well, we are testing both cyclophosphamide alone as well as testing no lymphodepletion at all. Those two cohorts will continue and we will make a decision on whether to continue both or select one based on the data. So the study is really not designed to select one, but it's really to test both different lymphodepletion and use that information as we expand the clinical study into other indications.

Speaker 1

Thanks very much.

Operator

One moment for our next question. Our next question comes from the line of Rene Benjamin from Citizens. Your line is open.

Speaker 7

Great, thanks for taking the questions guys. Maybe just a couple. About how many sites total are you now expecting in The US and worldwide for this study? Related to that, how many patients do you feel you'll ultimately need to screen to enroll the full two forty patients? And I guess as you kind of think about the workflow right now between a patient getting diagnosed and ultimately getting dosed with Semi Cell, can you just talk us through kind of how are investigators having this discussion?

Speaker 7

How long does it take for a patient to kind of agree? And maybe what are the main reasons for patients not agreeing to move forward with ALPHA-three? Thanks.

Speaker 3

Randy, this is Zach. So I'd say standby on further details around our global expansion. I can say that in North America, we're shooting for around 50 plus or minus, and we're getting very close to that now within North America. And we've got a handful of sites in Canada that we expect to start activating very soon. As we push beyond the North American borders, we'll begin to as we have those details, we'll begin to share those as they come online.

Speaker 3

So standby for a clearer answer on that. As far as how many patients do we expect to screen, so we know that thirty percent to forty percent of patients with LBCL eventually will go on to relapse. In our modeling, we have anticipated somewhere around one in five or so would be MRD positive. And this is of course based on a clinical trial population. There are different pockets of risk based on what kind of a patient you are.

Speaker 3

But as we screen more and more patients, we will begin to refine that number and be able to understand it better. But we've modeled it around that target. And then finally, the question around how are patients being approached with potential enrollment. There has been some refining of the pitch per se, but there plenty of our investigators, both principal and sub investigators at sites, that came very naturally to this and introduced this to the patients right as they were coming in for their very first dose of R CHOP, or even more commonly at the time of an interval scan. And so actually, it's those best practices that we've now been able to propagate across the rest of the activated sites.

Speaker 3

And so we are more and more talking to these patients right at the beginning because what we were finding was that if we didn't do that, the patients got to the end of their treatment course and they were just expecting a PET scan. And if the PET scan was a complete remission, they thought they were done. And so getting ahead of that and saying, well, PET scans are not so specific and not so sensitive and we have a better test that we want to do at the end of your treatment, that has led to a lot better conversion of patients who are signing consent to screen. So we have gotten much, much better at that.

Speaker 6

Great. Thank you.

Operator

One moment for our next question. Our next question will come from the line of Jack Allen from Baird. Your line is open.

Speaker 8

Hey, everyone. This is Nick on for Jack. Thanks for taking our question. With recent turnover at FDA and Seaver, new Seaver Director of Vinay Forsad impacting clinical trial designs going forward, I know one of my peers asked about any potential impacts to alpha-three, but what are your expectations surrounding how these changes could impact the autoimmune opportunity cell therapies? Thanks.

Speaker 2

Yes. Here I think there are so many speculations out there about how new director at CEVA may influence what goes on in the cell therapy and rare diseases. But all my experience, FDA is an institution. There is a director, there are medical reviewers that abide by the guidance document that exists that dictates how they should be reviewing the clinical data and programs. So when I sort of think about the institutional, the knowledge within the FDA, plus the fact that in autoimmune diseases, the clinical endpoints always has been never been survival.

Speaker 2

It's a symptom improvement. I know there's a lot of discussions about the emphasis that Doctor. Prasad has put on overall survival in the hematology oncology trials. But that's not the case in the autoimmune disease indications. To me, if anything, provided that the safety and efficacy meets the criteria, I do not see any problems of advancing CAR T products or for that matter, any other new modalities such as T cell engagers or even in vivo CAR T treatment into the autoimmune indications.

Operator

Thank you. One moment for our next question. And our next question will come from the line of Salveen Richter from Goldman Sachs. Your line is open.

Speaker 9

Hey, everyone. This is Mark on for Salveen. Thanks so much for taking our question. So back to the autoimmune dataset. Given the push to first half of twenty six, how much additional follow-up would this provide?

Speaker 9

Could we see like six months of follow-up, for example? And also, what additional clinical information are you hoping to show? Could we see like fleet eye score? And will you show a side by side comparison of data from the cyclophosphamide versus no lymphodepletion regimen? And finally, what is the bar for success here in your view, kind of noting that some of your competitor allogeneic CAR T players will likely have some first autoimmune data by then?

Speaker 2

Mark, great question. That's a very loaded question. Give us a time to enroll the patients. And as we always have said, dose escalation study, it takes time to enroll the patients. There'll be a handful of patients based on which we believe that we can provide both clinical as well as the biomarker driven data.

Speaker 2

And obviously, when we push out the data communication from the year end to the first half, the follow-up on these patients will be lengthened accordingly.

Speaker 9

All right. Thank you.

Operator

One moment for our next question. Our next question comes from the line of Sami Corwin from William Blair. Your line is open.

Speaker 7

Hi. This is Caleb on for Sami Corwin. Thanks for taking our question. So just a couple from us. Do you think there'll be any overlap in the site related challenges you saw for alpha three in the ex US sites?

Speaker 7

Or do you think they're a little bit more or less equipped at these centers? And then for 03/29, can you remind us if you plan to also activate ex US sites for the resolution study? Thanks.

Speaker 3

Hey, Caleb, this is Zach. So as we expand outside The U. S, I think things are going to be generally better than the first couple of months here in The U. S. For a few reasons.

Speaker 3

First, we're better at this now. We know exactly where the pitfalls are and we can address them proactively with the ex US sites. But likely those sites are going to be better equipped for a trial like A3 anyway because typically, all of the lymphoma care happens by the same doctors. So frontline, salvage, CAR T, transplant, they all are given in the same office, often by the same individuals. So the bifurcation of care that we've long known exists in The U.

Speaker 3

S. Is far less prevalent ex U. S. So for a few reasons, we expect that time from activation to robust screening activity to be shortened in the ex U. S.

Speaker 3

Territories. And then on the 03/29, do we expect similar delays on the ex U. S. With 03/29?

Speaker 2

Is that the second question, Caleb? What are we used to on ex U.

Speaker 7

Site, yes.

Speaker 2

Okay.

Speaker 3

Stay tuned on that one. I think we're still defining our regulatory and operational strategy. We're focused in the near term on U. S. Sites for 03/29.

Speaker 3

But given the competitive intensity, we are certainly open to considering expanding ex U. S.

Operator

Thank you. One moment for our next question. Our next question will come from the line of Astika Goonewardene from Truist. Your line is open.

Speaker 1

Hi, this is Karina for Astika. Thanks for taking the question. It seems like you guys are prioritizing SEMA cell and 29. How should we think about ALLO-three sixteen in Neucel? Has it been reprioritized?

Speaker 2

Great question. I fact is we have to prioritize. We will be presenting ALLO-three sixteen data as an oral presentation at ASCO. So let's see let's wait for that oral presentation and we'll provide additional guidance.

Speaker 1

All right. Thank you.

Operator

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

Speaker 10

Hi, guys. Thanks for taking my question. So, we've seen some really interesting and in some cases strong data from the autologous CAR Ts autoimmune disease. But one of the challenges we've heard is there's obviously a period where patients need to be basically off immunosuppressants and the CAR T is being made. And to that point, I'm just curious as to the approach that you're taking to taper immunosuppressants and also if you could just talk about the potential advantages that you have since maybe that period off immunosuppressants is going be a lot shorter.

Speaker 3

Hey, John. So the answer to your question, think I'll be able to tackle both with a single response. And that is, I think one of the great advantages of an off the shelf therapy like three twenty nine is that we can deliver it with minimal disruption to the standard care that the patients are receiving. So with autologous, you're absolutely right, they need to taper. But what many don't appreciate is they actually need to taper not once but twice.

Speaker 3

They to taper off immunosuppressants for collection and then again for infusion. For us, we can keep those immunosuppressants on right up until the last minute and then stop them and infuse ALLO-three twenty nine. In fact, that has turned out to be one of the several key differentiating advantages as we are approaching clinical trial sites proposing open this trial. It just feels like to them that this is going to fit much more naturally into the routine care of their patients.

Speaker 10

Great. Thank you.

Operator

One moment for our next question. Our next question will come from the line of William Pickering from Bernstein. Your line is open.

Speaker 6

Hi. Good afternoon. Thank you for taking my question. I understand you're not ready to share expectations on the conversion rate from consent to randomization, but it does sound like your assumptions are fairly conservative just given the two fifty percent of patients and your estimates for the positivity rate. So I was just wondering if you could describe how you see this conversion rate comping against other trials you previously had a part of and what may be some of the factors that might lead patients to not convert?

Speaker 6

Thank you so much.

Speaker 3

So I think we're seeing very good uptake at the sites, both by doctors and by patients. So when this study is pitched appropriately at the right time, as we discussed previously on the call, we're finding that most of these patients are signing up for treatment. It's a pretty clear, straightforward decision for them to make. Once they're found to be MRD positive, again, the vast majority of those patients are agreeing to undergo screening for the main study. Now there are a handful of screening tests.

Speaker 3

We actually consider them to be fairly straightforward. This is a frontline study. Most of these patients are pretty healthy. So we're not seeing many patients screen fail. Again, it's still relatively early days in the trial.

Speaker 3

And we'll have a lot more information later on. And of course, when we share the overall results of the study, all that will be detailed out.

Operator

Thank you. One moment for our next question. And our next question will come from the line of Robert Burns from H. C. Wainwright.

Operator

Your line is open.

Speaker 11

Good afternoon. This is Dan on for Rob. Thanks for taking our question. So in discussing your large inventory stock and the manufacturing rollback in relation to the capital allocation strategy, have you done any frozen cell stability testing on your products? And what's the approximate freezer shelf life of the cells?

Speaker 11

Thank you.

Speaker 2

Dan, this is Dave Chang. I'll take that question. In terms of the cell product, frozen stability tends to be pretty long, several years. What is being done is we carry out the stability test as time goes on. And the stability is established by how long that we have done the stability test.

Speaker 2

So there will be an ongoing process. And our expectation is that the inventory that we have on the current stability testing strategy will be sufficient to cover all the clinical studies that we are planning to do.

Operator

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

Speaker 2

Well, thank you, operator, and thank you everybody who participated in this call. I want to say that allergen was built to challenge convention and today that ambition is becoming reality. With ALPHA-three, we are changing the playbook in large B cell lymphoma. With ALLO-three 16, we are proving solid tumors that we didn't reach up cell therapy. And with ALLO-three 29, we are opening a bold new chapter in autoimmune disease.

Speaker 2

These aren't just ideas. These programs are backed by data and real potential to transform care. The path forward won't be easy, but we've never aimed for easy. We've aimed for impact and with focus, discipline and world class science we intend to deliver. Thanks for joining us.

Speaker 2

Operator, you may now disconnect.

Powered by Quartr

Key Takeaways

  • Allogene’s pivotal ALPHA3 trial in first-line large B cell lymphoma has nearly 50 activated US sites, over 250 patients consented for MRD screening, and now aims for lymphodepletion regimen selection and a futility analysis in the first half of 2026 after addressing site-level staffing delays.
  • ALLO-316 (TRAVERSE trial) is breaking ground in heavily pretreated advanced renal cell carcinoma with a 50% best overall response rate in CD70-high tumors, and updated Phase 1b data will be presented orally at ASCO on June 1.
  • The RESOLUTION trial for ALLO-329 in autoimmune diseases launches mid-2025 as a first-of-its-kind allogeneic CAR T basket study, including a no-lymphodepletion arm enabled by DAGGER technology, with proof-of-concept data expected in H1 2026 and partnership discussions underway.
  • Through targeted manufacturing cost savings and operational realignment, Allogene has extended its cash runway into the second half of 2027, reporting $335.5 million in cash and investments as of Q1 2025, with a full-year cash burn guidance of approximately $150 million and GAAP operating expenses of $230 million.
  • Allogene remains confident in an evidence-based regulatory pathway under the new CBER leadership, noting MRD is used for patient selection in ALPHA3 rather than as a surrogate endpoint and expecting oncology review to stay grounded in clinical benefit.
A.I. generated. May contain errors.
Earnings Conference Call
Allogene Therapeutics Q1 2025
00:00 / 00:00