Q1 2025 Allogene Therapeutics Inc Earnings Call
Thank you. Bye.
Hello, thank you for sending by and welcome to Allogene Therapeutics' first quarter, 2025 conference call.
After the speaker's presentation, there will be a question and answer session. As a reminder to ask a question, you need to press star 1-1 on your telephone and wait for your name to be announced.
Speaker Change: To withdraw your question, please press star one one again. Please be aware that today's conference is being recorded. I want to turn the call over to Christine Cassiano, Chief Corporate Affairs and Brand Strategy Officer. Miss Cassiano, please go ahead. Thank you very much.
Christine Cassiano: Thank you, operator, and thanks to all of you for joining us call. After the market closed, Allogene issued a press release that provided a business update and financial results for the first quarter of 2025.
Christine Cassiano: This press release and today's webcast are available on our website. Following our prepared remarks, we will host a Q&A session. We recognize that historically, questions have been multifaceted, but note that we will endeavor to keep this call to under an hour. We will host a Q&A session.
Christine Cassiano: I'm joined today by Dr. David Chang, President and Chief Executive Officer, Dr. Zachary Roberts, Executive Vice President of Research and Development and Chief Medical Officer, and Geoff Parker, Chief Financial Officer.
During today's call, we will be making certain forward-looking statements. [inaudible]
Christine Cassiano: These may include statements regarding the success and timing of our ongoing and planned clinical trials, data presentations, regulatory filings, future research and development efforts, manufacturing capabilities, the safety and efficacy of our product candidates.
Commercial Market Forecast, and Financial Guidance among other things.
Christine Cassiano: These four-looking statements are based on current information, assumptions, and expectations that are subject to change.
Christine Cassiano: A description of these potential risks can be found in our press release and latest FCC disclosure documents. You're a caution not to place undue reliance on these forward-looking statements, and alleging explains any obligation to update these statements. I'll now turn the call over to David.
Thank you, Christine, and welcome everyone. Thank you, everyone.
David: 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.
David: At the time, we committed to doing what no Cartier done before.
David: That strategy wasn't about being autologous or allogeneic. It was about breaking boundaries. Ibanez, Ibanez,
David: One year later, that decision looks not just bold but present. Thank you.
David: I believe we have built something extraordinary, especially for a small biotechnology company in the current market environment. [inaudible]
We have a trio of highly differentiated clinical assets.
Each with a potential to be transformative. That's it.
David: Combined, they demonstrate that Allogene is potentially changing the trajectory of South therapy.
David: At the center of that vision is Alpha 3, pivotal first-line consolidation trial with Semenkow, which we believe will transform care in large BCL Informa.
and Open the Door for Community Cancer Centers.
David: The use of MRD paired with first line treatment consolidation is a radical departure from traditional approaches. Thank you.
And it's gaining powerful traction.
David: What one seemed ambitious is not being embraced across nearly 50 activated US sites. [inaudible]
David: Investigators recognize that Alpha 3 is not just another Carti Study. It seeks to redefine how to identify and when we treat high risk patients. [inaudible]
David: That recognition is reflected in the collaboration we are seeing across sites, many of which are proactively developing and sharing patient identification strategies. Thank you very much.
Launching this groundbreaking trial has come with important lessons.
David: 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 pat CT scan.
David: These insights are now guiding smarter enrollment tactics, more effective communication with patients, and more precise forecasting. [inaudible]
David: The result has been tangible. To date, over 250 patients have consented for MRD screening with nearly half in the last three months.
David: 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. Thanks.
David: We have shifted the Limport depletion regimen selection and fertility analysis milestone into the first half of 2026.
David: While that's two quarters later than planned, it reflects a strategic decision to prioritize precision, insight, and a stronger foundation for a future commercial launch.
David: During this time, we are also actively evaluating what data will be most meaningful to share at the time of the lymphodiposition selection and fertility analysis.
in response to feedback from stakeholders.
David: I'll go through one six in the traverse trial, continues to break new ground, showing signs of efficacy in patients with heavily pre-treated advanced renal self carcinoma. [inaudible]
David: These patients are highly refractory to treatment, and often only have months to live.
David: For these patients, Ella 316 may offer something they never thought possible. Hope.
With our CD-70 targeted data technology.
David: SALO 316 is providing a clear demonstration of potential that CAR T holds in solid tumors.
Something that feels long viewed as aspirational.
Speaker Change: Zach will comment photo on Alokoo on 6th, and now a coming oral presentation at ASCO on June 1st.
Speaker Change: In the resolution trial, launching mid 2025, hour three to nine is poised to change how we treat autoimmune disease. [inaudible]
Speaker Change: This dual-targeted, Alginate Cartier product offers the potential to eliminate lymphodiplation entirely. Thank you very much.
which is a major hurdle to broader cardiac adoption. [inaudible]
Speaker Change: 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 scorsis. [inaudible]
Speaker Change: As we move our trials forward, we are keenly aware of the macroeconomic environment.
Preserving our cash runway remains the top priority.
with a refined operational strategy and efficiency driven cost realignment. Thank you very much.
Speaker Change: We have extended our cash runway into the second half of 2027. We have extended our cash runway into the second half of 2027.
Speaker Change: This gives us the ability to weather market headwinds as we drive ahead to our most promising clinical
The field of cell therapy is evolving.
Speaker Change: The autologous versus allogeneic debate is giving way to a bigger question.
How broadly can car TV applied?
That Allogene.
Speaker Change: We are answering that question with action. Our strategy, set in motion in January 2024, was never about following existing models.
Speaker Change: It was about doing what had never been done before, and importantly, making car key more accessible by harnessing the unique advantages, only an allogeneic approach can deliver.
with Alpha 3, ALO 316, and ALO 329.
Speaker Change: We believe we are proving that CARTI is not just about self-tight or delivery mechanism.
Speaker Change: It's about clinical ambition, rearward insights, and building a scalable future for patients who need more than incremental change.
Speaker Change: Finally, while it is unusual for me to use our quarterly quote to address some of the macro issues impacting our industry, it is more important ever to take a moment to do so.
Speaker Change: Like many in the industry, we are serving the evolving landscape at FDA and assessing potential implications, granted in our continued confidence in the agency's mission, scientific integrity, and dedication to patient-centered progress.
Speaker Change: The selection of Dr. Vinay Prasad, a well-known voice on drug development reform, has sparked a range of reactions, but in moments like this, it is important to take a breath and recognize the broader context.
Speaker Change: While Dr. Prasad has been a provocative voice at times, he has also long advocated for rigor, transparency and patient-centered outcomes, value we share.
Speaker Change: It is also worth remembering that the clinical review of oncology products, including those on the seabird, continues to rest with oncology center of excellence.
Speaker Change: That structural continuity should offer some reassurance that therapeutic evaluation will remain grounded in science? Yes.
Presidents and patient need. [inaudible]
Speaker Change: Rather than speculate, how approach will be to engage, educate and collaborate. [inaudible]
Speaker Change: If this marks a new chapter in regulatory thinking, we intend to be a constructive part of that dialogue. Thank you very much.
Ultimately, we believe that strong science. Yes.
Speaker Change: and Meaningful Clinical Benefit will continue to carry the day, and we remain confident in the value of our programs to patients who need better options. Thank you very much.
On all front, we believe Allogene has a responsibility.
Speaker Change: Not just to participate in the future of medicine, but to lead, to help shape and define it.
Zach: I would like to now hand the call over to Zach. Thank you.
Zach: Thank you, David. As David chaired, this is a pivotal time for allergy, not just in terms of vision but execution.
Zach: The practice 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.
Zach: Let's begin with Alpha 3, where the enthusiasm we're seeing from nearly 50 activated sites across the US is not only sustained, it is growing here and internationally.
Zach: This trial represents a true paradigm shift. 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.
Zach: But as first movers, we've also encountered realities that no modeling could fully anticipate.
Zach: Site-level operational constraints, including staffing shortages and administrative hurdles, led to slower than expected transitions from site activation to patient screening.
Zach: Biprotation 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.
Zach: Well-worn monologues, given the 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.
Zach: 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. Thank you very much.
Zach: Those investments are working. As David noted, with improved sights and patient engagement and education, we have now consented over 250 patients for MRD testing since the start of the trial.
Zach: With robust month-over-month improvement in the screening rate, especially since the earliest site 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.
Zach: Furthermore, many sites are sharing best practices with one another, an encouraging sign that this trial is building momentum.
Zach: 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.
Zach: 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 3. The first XUS sites, we will launch our in Canada, which are on track to activate in the next several weeks. The first XUS sites, we will launch our in Canada, which are on track to activate in the next several weeks.
Zach: Turning to ALO 316, this program continues to challenge expectations for CAR-T and Salah tumors. We're excited that the updated results from the Phase 1-B expansion cohort will be featured and an oral presentation of ASCO on June 1st.
Zach: This data will be presented in the Main Kidney and Bladder Cancer Session at ASCO, alongside updates of pivotal datasets and cutting-edge combination trials presented by respected leaders in RCC. That alone signals how important this data could be to the field.
Zach: What makes ALO 316 so compelling is that it is one of the very small handful of CAR-T therapies and the first Allogeneic to demonstrate meaningful activity in solid tumors with just a single infusion. [inaudible]
Zach: To achieve this, especially with a standard lymphodopleasing regimen, puts Allen 316 in a class of its own.
Zach: That ALO 316 achieved this in a patient population as sick and heavily pretreated as these Phase 1B patients, which may be some of the most treatment refractory patients ever studied in RCC is truly groundbreaking. . . .
Zach: In our data cut presented at SITSI last November , eight patients were treated in the Phase I B Expansion cohort.
Zach: In the six of these heavily pre-treated patients whose tumors expressed high levels of CD-70, we observed that 50% best overall response rate and a 33% confirmed response rate results that we believe underscore the promising potential of this therapy.
Zach: The upcoming ASCO presentation will build on those results with additional patients treated and longer-term follow-ups of the results presented at 50.
Zach: Key translational findings, including the role of our CD-70 targeted dagger technology in promoting car T-cell expansion and persistence, reveal a mechanistic basis for the clinical results and give us confidence that ALO 316 could be a blueprint for car T and solid tumors more broadly.
Zach: 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.
Zach: Finally, I want to briefly touch on ALO329 and our progress in autoimmune disease.
Zach: This is a new frontier for self therapy, and Allo 329 is engineered for it. [inaudible]
Zach: The Phase I Resolution Trial, launching mid-year, 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 316.
Zach: We expect proof-of-concept data, first half, 2026, as we apply our experience with Alpha 3 and the potential for delays to patient screening activity following side activation.
Zach: But the most important takeaway is our continued belief that this trial can unlock significant potential across a broad spectrum of immune-mediated diseases.
Zach: In summary, the Allogene story today isn't just about bold ideas, it's about a growing body of evidence that Allogene at Carti is no longer a theoretical promise, but a transformational reality on the verge of reshaping the field. [inaudible]
Zach: 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 milling disease and solid tumors in an autoimmune disease. [inaudible]
With that, I'll hand my call over to Geoff.
Geoff: 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 2027.
Geoff: 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.
Geoff: These programs are not merely aspirational. We believe they are on the cusp of potentially delivering transformative outcomes for patients.
Geoff: That creates both the responsibility and an opportunity to our patients and to our shareholders to see them through.
Geoff: 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.
Geoff: We are fortunate to have sufficient inventories of Semicel, ALO 329, and ALO 316. Next.
Geoff: to supply our ongoing alpha-3 resolution and perverse trials. Reflecting the inherent efficiencies of producing an Allogeneic CAR-T product, including the ability to manufacture product well in advance. Thank you very much.
Geoff: As a result, we can implement these targeted cost savings initiatives without impacting trial conduct.
Geoff: 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. [inaudible]
Geoff: 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.
Geoff: As of March 31st, 2025, we had $335.5 million in cash, cash equivalents and investments.
Geoff: Our research and development expenses for Q1 2025 were $50.2 million, including $5 million in non-cash stock based compensation expense. [inaudible]
Geoff: General and administrative expenses for Q1 2025 were $15 million, including $7.1 million in non-cash stock-based compensation. Thank you very much.
Geoff: Our updated guidance for 2025 is an expected cash burn of approximately $150 million.
Geoff: We expect full-year 2025 gap operating expenses to be approximately $230 million, which includes an estimated non-cash stock-based compensation expense of approximately $45 million. $20 million.
This guidance excludes any impact from potential business development activities.
We'll now open the call for questions.
Thank you. Bye.
and their families. Thank you. Thank you.
Geoff: Thank you. As a reminder to ask a question, you need to press Star 101 on your telephone, and wait for name to be announced to a draw your question, please press Star 101 again. Please send by Wilkinson, Paula de Cune, Roster, one moment for our first question.
Speaker Change: Our first question will come from the line of Michael Yee from Geoffrey's. Your line is open.
Thank you, good afternoon. Good afternoon.
Speaker Change: 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.
Speaker Change: Could you explain what the issue is and how you think that's resolved? What's going on?
Speaker Change: And as part two about same question, when you talk about 250 people that have been consented to screening,
Speaker Change: That means they're consenting to be tested. That doesn't necessarily mean that they're actually going to get into the study. So as you're timing of the interim based on a whole bunch of assumptions, including how many people will be positive and then actually have to enroll into the study. Thank you.
Thank you very much.
Speaker Change: Michael, thanks for your question. Let me take the first one and I'll ask Zach to answer your second question.
Speaker Change: In many ways, after three studies, from the beginning, there were some puzzling findings. Thanks.
Speaker Change: What we found was the excitement and enthusiasm that we are seeing from the investigator. The investigator.
Speaker Change: As we have previously stated, that was far above any other experience that I had personally had in doing a clinical studies. [inaudible]
Speaker Change: On the other hand, the actual delivery of the, you know, the site, you know, the enrollment then in a patient screening from the site. There was a lag that we just could not understand. And...
But as the study evolves and progresses...
Speaker Change: 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. [inaudible]
Speaker Change: So this is the disconnect that we are trying to understand. And now we are, you know, enough into the study that we clearly understand what was going on. It was purely sight related issues that as three to four months from the
Speaker Change: Side Activation. You know, this is essentially getting all the paperwork completed. David Chang, David Chang, David Chang,
Speaker Change: Two 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...
Speaker Change: Boba Pastry Reformat that has been very consistent and now meeting all the initial assumptions that we are making under study. And I would also say that as we are looking into expanding study outside the US. And I would say that as we are looking into expanding study outside the US.
Speaker Change: The investigator enthusiasm for opera 3 study is just as high as ever that I've seen. And this is one of the positive things. So, you know, what do I think? This is a definitely study that is doable. All right.
Speaker Change: 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. So that's what's going to happen in the future.
Thank you.
Speaker Change: And Mike, I'll add to that, that, you know, really speaking to what David just outlined, the fact that we've seen such a...
Speaker Change: 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.
Speaker Change: That really has been quite validating of that observation that we were making, that that was a little bit of a slow start, but the sides and the enthusiasm. The enthusiasm.
Speaker Change: that they've had from the beginning is now translating directly into screening activity, as far as the question around.
Speaker Change: The 250, you are correct, that doesn't mean that there are 250 patients that are ready to undergo randomization. That is the number of patients that are undergoing consented to screen for the MRD test. Now, of course.
Speaker Change: We need that number to 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 enrollment.
Thank you.
Thank you. All moments for our next question.
Speaker Change: Our next question will confline out Tyler Van Buren from T.D. Calvin. Carolina is open. [inaudible]
Speaker Change: Hey guys, thanks very much for the questions. The first one related to alpha 3, of course. Sorry, you think it's a significant difference in the occurrence of these site-related factors that community versus the more academic sites. And what do you believe is the probability that we still get an interim EFS readout from alpha 3 by the end of. Thank you very much.
Speaker Change: Next year. And then the second one, just to follow up on your Dr. Prasad comments, given his point of seabird, been critical on MRD, so it'd be helpful if you could elaborate and why those don't necessarily apply to the Alpha 3 clinical trial program.
Speaker Change: Tyler, great questions. Let me take the second one, since I made some comments about new director of the sweeper in my prepared statement, and I'll ask that to cover the first question.
My belief is you know, always been that FDA. Okay.
Speaker Change: They are used evidence-based approach. I mean, that is by 20 plus years of experience, you know, some were very contentious discussions that I have had with FDA, but at the end, what prevails is evidence-based discussion and meaningful clinical benefit that you can demonstrate. Thank you very much.
Speaker Change: You know, the particular question of MRD, that, you know, have to say that, you know, in our study for Alpha 3 study.
That doesn't really apply. Bye.
Speaker Change: MRD in Alpha Tree 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. Dr. Johnson, Dr. Johnson, Dr. Johnson, Dr. Johnson,
Speaker Change: And this will be somewhat akin to using other clinical risk stratifications or any other things that people have been using all throughout drug development and oncology to identify high patient risks.
Speaker Change: 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 Botalus Carti. So, you know, back to your question around, you know, MRD as a surrogate endpoint. Thank you very much.
Speaker Change: Now that obviously there's a lot of discussions that are ongoing. Thank you very much. Thank you.
Speaker Change: And I do hope that in the future that there is enough evidence to elevate MRD as a surrogate endpoint, even full non-Hachkinson format. But as I said, it is not directly relevant to what we are doing. Thank you.
Another thing that I would say about the evidence-based approach.
Thank you.
Speaker Change: Let's not forget that alpha-3 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 are evaluating a new treatment or unapproved product. 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 Change: I think all these are 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, you know, of Alpha 3 under the new leadership at CBER.
Thank you.
Speaker Change: 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.
Speaker Change: 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, they are screening patients very aggressively. [inaudible]
Thank you.
Speaker Change: And then, let me just finish up your question about the event free survival towards the year and, you know, of 2026. At this point, you know, we are intentionally remain silent beyond what we have said, which is communicating the length of depletion and fertility analysis data in the first step.
Speaker Change: At that time, we will definitely have a lot more clarity on the interface of the study, and we plan to provide additional guidance in overall study.
Speaker Change: You know, together with Lympho Depletion, and as we have said in the prepared statement...
Speaker Change: We are looking into a ways to make the info depletion 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. Thank you very much.
Very interesting. Thank you.
Thank you. One moment for our next question.
Byron Ahmed: Our next question will come from Biren Amin, from Piper Sandler, the line is open. Thank you very much.
Byron Ahmed: Yeah, hi guys. Thanks for taking my questions. Just on the Alpha 3, do you believe all sites have sufficient site staffing currently compared to I guess, you know, I guess when you first initiated the study. [inaudible]
Byron Ahmed: And then I guess a couple of other questions around the trial. What's the conversion rate from consent to randomization and what's the average time that it takes a patient to go from consent to randomization? Thanks.
Speaker Change: Hey, Buren. So, with respect to your first question, are sites adequately staffed that would say generally yes?
I think part of what we saw was...
Speaker Change: Then having to get kind of internal regulatory sign-offs and operational pieces in place, get the study.
Speaker Change: You know, more or less it is up and running very nicely now across the sites. Of course the ones that are coming on most recently. Ibanez.
Speaker Change: 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. [inaudible]
Speaker Change: As far as the other two questions around conversion rate and time from screening to randomization.
Speaker Change: 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 get that kind of granularity, but I'll say if David, if there's anything else you want to add to that.
Speaker Change: Yeah, I mean, you know, Buren, I mean, in terms of sightstacking. [inaudible]
Speaker Change: Yes, a site, you know, you know, step up, but I'm not a thing that is helping us quickly.
Speaker Change: is doing the course of trying to travel should what was going on. [inaudible]
Speaker Change: We have had multiple discussions with investigators and investigators themselves coming up with ideas.
Speaker Change: about how to identify patients who could be eligible from the study. You know, this entails looking at not just patients who are coming into the clinic.
Speaker Change: But looking at their own database, appointment books and others, and I would say that is also helping greatly, and these are the kind of the learnings that...
Speaker Change: And, you know, conversion rate, I mean, that, you know, as Zach said, we're going to sort of differ, you know, providing that detail, but in terms of timing.
Keep in mind when somebody...
Speaker Change: Consent to undergo MRD testing. That is any time during the 12 weeks of the frontline largely selling former treatment.
So, 12 weeks of 18 weeks.
Speaker Change: Charles Aiken weeks up from my treatment. So, we have to wait for them to complete, and, you know, sometimes people consent when they're beginning. Sometimes they consent what was then. So, there is a little bit of variability. And, you know, there's a little bit of variability.
Speaker Change: And once they undergo MRD testing, you know, so far, the metrics on MRD testing has been working as great.
It still takes another two to four weeks. Ibanez, Ibanez, Ibanez, Ibanez, Ibanez,
Speaker Change: After identifying MRD positive patients to get the logistic dates taken care of to randomize those patients.
Speaker Change: So these are the things that, in retrospect, we have not fully bedded into the timeline of the study, which is the reason that we are pushing out the link for the portions selection timeline by two quarters. First.
Perfect, thank you.
Thank you.
Thank you, one moment for our next question.
Speaker Change: Our next question comes from Brian Chang from J.P. Morgan. Your line is open.
Brian Chang: Hey guys, thanks for taking a question today. This too from us. It seems that you still have a bit of a gap to unroll the first 36 patient.
Speaker Change: First is that, you know, it's the lack in screening that attributed to the three to four months of delay, more concentrated in the community-based sites.
Speaker Change: And then second, you related to the expansion to the international sites. How may 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 FDAC back on this? The FDAC, the FDAC, the FDAC, the FDAC.
Speaker Change: 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?
Speaker Change: Um, differences in the community versus academic, and I, I, the answer to that question is no, but let me pause to see, is that what you were asking, whether we're seeing a difference in the, in activity that are in a community versus academic. Yes, that's correct. Yeah.
Speaker Change: 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 CARTI experience. So...
Speaker Change: All of the things that we found attractive about Alpha 3 are playing out very, very nicely in this study.
Speaker Change: As far as our expansion into the XUS territories, will that introduce heterogeneity into the patients? The short answer to that question is no. And the reason is quite simple. Our chop is the global standard for frontline DLBCL treatment, full stop.
Speaker Change: Very few regions even have a second alternative like Polar Chip. So if anything, it will increase the homogeneity in terms of what that prior therapy is in those XUS territories. Thank you very much.
All right, thank you. One moment for our next question.
Matthew Biegler: Our next question will come flying to Matthew Biegler from Oppenheimer, Atlanta's Open. [inaudible]
Speaker Change: Thanks for the question. I wanted to maybe ship things and ask about the eye and eye strategy. David, it sounded like at least from the prepared remarks you're being. Thank you very much.
Speaker Change: Pretty cautious on the burn, and obviously, you know, Ina as a big component of that burn. 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.
Thank you very much.
Speaker Change: You know, on the different market environment, my answer within, you know, different, but in the current market in a situation, you know...
Really protecting the cash runways the key.
Speaker Change: So, if there is any kind of reasonable deal to be had, we will, we have indicated in a previously that, you know, we are very, you know, willing to partner and the risk, you know, the autoimmune program, especially given that this is not our core therapeutic area of expertise. Please.
And in terms of pushing the...
Speaker Change: Timeline from the year end to the first half. I think this is just a little bit more, you know, you know, providing little more caution, but also it's factoring in, you know, the feedback that we've been getting, you know, from the investors previously we will focus on. Thank you very much.
Just using the biomarker data as a proof of concept.
Speaker Change: But some of the consistent feedback that we have gotten from the investigators will...
Speaker Change: Yeah, but you know, you want to see a little bit more there, you got to have some clinical responses as well. So, you know, just to do both. You know, having little more cautious and a little bit of buffer, as well as...
Speaker Change: Giving the clinical came opportunity to include the clinical update on the patients who are treated, that's the reason that we are pushing out the timeline for the profile concept data from three to nine to the first half.
Speaker Change: I would just add, I mean, we are in the midst of site identification and activating the clinical trial sites for the...
Speaker Change: The Outlet Week Tonight Study, and that process is going exceedingly well, and we feel very optimistic, as well as we are very enthusiastic about this program. Thank you very much.
Appreciate it.
One moment for next question.
Speaker Change: Our next question will come flying to Samantha Semenkow from City, Elan is open. Thank you very much.
Speaker Change: 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 3 as it comes to staffing issues. Thanks very much.
Speaker Change: You know, not only is the site staffing issue, we have to bring together self-darkest, as well as rheumatologist on the same room to be able to conduct the study. So there is the added logistical challenges of doing the autoimmune studies with a CAR-T. [inaudible]
Speaker Change: And in terms of the expected data, you know, this is a dose escalation, you know, you know, as well as testing tool for depletion regimen. [inaudible]
Speaker Change: In terms of the number of patients that we can reasonably treat.
Speaker Change: It will be a handful of patients, because there is a weight period between first and subsequent patients at each dose level, as well as weight time between escalating from one dose level to another.
Speaker Change: And you had a question about are we going to make any lympho-depletion selection regimen? Well, we are testing both cyclophosphate alone, as well as testing no lympho-depletion at all. [inaudible]
Speaker Change: Those two cards will continue and we will make a decision on whether to continue both. Both.
Speaker Change: Or Select One, based on the data. So, you know, the study is really not in a design to select one, but it's really to test both different for depletion and use that information as we expand the clinical study into other indications. Let's go.
Thanks very much.
One moment for the next question.
Speaker Change: Our next question comes from Ryan of Reni Benjamin from Citizens, Uranus Open. [inaudible]
Rennie Benjamin: 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?
Rennie Benjamin: Related to that, how many patients do you feel you ultimately need to screen? [inaudible]
To enroll the full 240 patients.
Rennie Benjamin: And I guess as you kind of think about the workflow right now between a patient getting diagnosed and ultimately getting dose to what's MSL, can you just talk us through kind of, you know, how are investigators having this discussion? How long does it take for a patient? [inaudible]
Rennie Benjamin: To kind of agree, and maybe one of the main reasons for patients not agreeing to move forward with Alpha 3. Thanks.
Hey, Reni, this is Zach, so...
Speaker Change: I'd say stand by on further details around our Global Expansion.
Speaker Change: 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.
Speaker Change: 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. So stand by for a clearer answer on that.
Speaker Change: As far as how many patients do we expect to screen? [inaudible]
Speaker Change: So we know that 30 to 40% of patients with LBCL eventually will go on to relapse.
Speaker Change: 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. [inaudible]
Speaker Change: And 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.
Speaker Change: And then finally, the question around how are patients being approached with potential enrollment? Thank you very much.
Speaker Change: It's actually, you know, there has been some refining of the pitch per se, but there are plenty of our investigators, both principle and sub-investigators at sites. [inaudible]
Speaker Change: That came very naturally to this and introduced this to the patient's right as they were coming in for their very first dose of of our chopped.
Speaker Change: or even more commonly at the time of an interval scan.
Speaker Change: And so actually it's those best practices that we've now been able to propagate across the rest of the activated sites. And so we are more and more talking to these patients right at the beginning. Thank you very much.
Because...
Speaker Change: 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. [inaudible]
Speaker Change: And so, getting ahead of that and saying, well, PET scans are not so specific and not so sensitive, but 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 screens. So, we've gotten much, much better at that. Thank you very much.
Okay, thank you.
One moment for next question.
Speaker Change: Next question, conflina, Jack Allen from Bear, your line is open. [inaudible]
Speaker Change: Hey everyone, this is Nick on for Jack, thanks for taking our question. So with recent Turner FDA and Seaver, New Seaver Director of INAPRASAD impacting clinical trial designs going forward, I know one of my peers asked about any potential impacts to alpha-3, but what are your expectations surrounding how these changes could impact the autoimmune opportunity cell therapies. Thanks.
Thank you. Thank you.
Yes, so can I hear? [inaudible]
Speaker Change: I think, you know, there are so many speculations out there about how, you know, new director at CIBER may influence what goes on in the self therapy and rare diseases.
Speaker Change: But, you know, all my experience, you know, FDA is an institution. Thank you, Chef.
There is a director, there are medical reviewers. [inaudible]
Speaker Change: 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 knowledge within the FDA. Ibanez.
Plus the fact that in all reunion diseases. These diseases.
Speaker Change: You know, the clinical and points, you know, always has been, you know, never been survival. It's a symptom improvement. [inaudible]
Speaker Change: I know there is a lot of discussions about the emphasis that Dr. Prasad has put on overall survival in the hematology oncology trials, but that's not the case in the Orem in a disease indications.
Speaker Change: You know, to me, if anything, you know, provided that the safety and efficacy meets the criteria.
Speaker Change: I do not see any problems of advancing in a CARCY products, or for that matter any other new modalities, such as T-cell engages, or even imbibble in a CARCY treatment into the autoimmune indications. Thank you very much.
Thank you.
Thank you, one moment for our next question. Thank you.
Thank you.
Salveen Richter: Our next question will come flying out of Salveen Richter from Goldman Sachs.
Salveen Richter: Hey everyone, this is Mark on First Salveen. Thanks so much for taking our question. So back to the autoimmune data set, given the push to first half of 26, how much additional follow-up would this provide? Could we see like six months to follow, for example? And also what additional clinical information are you hoping to show? Could we see like, Sweet Eye Score?
Salveen Richter: And will you show a side-by-side comparison of data from the cyclophosphamide versus no lymphodipleicin regimen? And finally, what is the bar for success here in your view? Kind of noting that some of your competitor, Allogene Karte...
Players will likely have some first autoimmune data by then. [inaudible]
Speaker Change: Mark, great question, that's very loaded question. Question, question, question, question.
Give us a pie to involve the patients. Let's see what happens.
Speaker Change: And as we always have said, you know, in a both 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, you know, both clinical as well as the biomarker driven data. And obviously when we push out the data communication, you know, from the year end to the first half, the follow up on these patients will be lengthened accordingly. Thank you very much.
All right, thank you.
A moment for next question.
Speaker Change: Our next question comes in line of Sammy Corwin from William Blair. The line is open.
Speaker Change: All right, this is Caleb Wong for the same recording. Thanks for taking our question. So just a couple from us.
Speaker Change: Do you think there'll be any overlap in the site related challenges you solve for Alpha 3 in the XUS sites? [inaudible]
Speaker Change: What do you think they're a little more or less equipped at these centers? And then for three to nine key reminders to be planned to also activate XUSI's for the resolution study. Thanks. Thanks.
Speaker Change: Caleb, this is Zach. So as we expand outside the US, I think things are going to be generally better than the first couple of months here in the US.
Caleb Vaughn: For a few reasons, first, we're better at this now. We know exactly where the pitfalls are, and we can address them coactively with the XUS sites.
Caleb Vaughn: But likely those sites are going to be better equipped for a trial like A3 anyway, because typically it's all of the lymphoma care happens by the same doctors. So frontline, salvage, CART, transplant, they all are given in the same office, often by the same individuals.
Caleb Vaughn: So the bifurcation of care that we've long known exists in the US is far less prevalent XUS. So for a few reasons we expect that time from activation to robust screening activity to be shortened in the XUS territories. Thank you very much.
Caleb Vaughn: And then on the 329, do we expect similar delays on the XUS with 329? Is that the second question, Caleb?
Speaker Change: What are we are using? Okay, so. So.
Speaker Change: Stay tuned on that one. I think we're still defining our regulatory and operational strategy. We're focused in the near term on US sites for 329, but given the competitive intensity, we are certainly open to considering expanding XUS. Thank you very much.
Thank you. One moment for next question. Thank you.
Speaker Change: Our next question will come from the line of Athica Gunwardine from Truist. Your line is open.
Speaker Change: Hi, this is Christina for Asthika. Thanks for seeing the question. It seems like you guys are prioritizing CMSL and ALO329. How should we think about ALO316 from your cell has it been prioritized?
Thank you very much.
Speaker Change: Great question. I mean, you know, you know, the fact is we have to prioritize, we will be presenting AL-316 data as an oral presentation and ask. So, you know, let's see, you know, let's wait for that oral presentation and we'll provide, you know, additional guidance.
All right, thank you.
Thank you. One moment for the next question. Thank you very much.
Speaker Change: Our next question comes line of John Newman from Canacor Genuity. The line is open.
John Newman: I guess, thanks for taking my question. So, you know, we've seen some really interesting.
But one of the challenges we've heard is...
John Newman: There's obviously a period where patients need to be basically off immunosuppressants. [inaudible]
John Newman: The Cartier is being made into that point. I'm just curious as to the approach that you're taking, the table of immunosuppressants. And also, if you could just talk about the potential advantages that you have since maybe that period of immunosuppressants is going to be a lot shorter. [inaudible]
John Newman: 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. What many don't appreciate is actually need to taper not ones but twice. They have to taper off immunosuppressants for...
John Newman: 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 ALO-329. Thank you for your time, and I'll see you in the next video.
John Newman: In fact, that has turned out to be one of the several key differentiating advantages as we are approaching clinical trial sites proposing that they 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. [inaudible]
Great, thank you.
One moment for next question.
Speaker Change: Our next question of conflina, William Pickering from Bernstein, Elias Open. Thank you for your time.
Hi, I get afternoon. Thank you for taking my question.
Speaker Change: I understand you're not ready to share expectations on the conversion rate and consent to randomization, but...
Speaker Change: It does sound like your assumptions are fairly conservative, just given the...
Speaker Change: The 250% of patients and your estimates for the positivity rate. So I'm just wondering if you could describe how you see this conversion rate copying against other trials you could be in part of and what maybe some of the factors that might lead patients to not invert. Thank you so much.
Thank you.
So, I think...
Speaker Change: We're seeing very good uptake at the site, both by doctors and by patients. So when this study is pitched appropriately at the right time, as we discussed previously on the call,
Speaker Change: We're finding that most of these patients are signing up for treatment. It's a pretty clear, straightforward decision for them to make.
Speaker Change: Once they're found to be MRD positive, again, the vast majority of those patients are agreeing to undergo screening for the main study.
Speaker Change: Now, there are a handful of screening tests. We actually consider them to be fairly straightforward. This is a frontline study. Most of these patients are pretty healthy. Thank you.
So, we're not seeing many patients screen fail again.
Speaker Change: It's still relatively early days in the trial, 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. Thank you.
Um...
Thank you. One moment for our next question. Let's begin.
Robert Burns: In our next question, we'll come flying to Robert Burns from AT-1 Wright. The line is open.
Speaker Change: Good afternoon, Mr. Dan on Farab. Thanks for taking our question.
Robert Burns: So, in discussing your large inventory stock and the manufacturer and rollback relation of the capital allocation strategy, have you done any frozen self stability testing on the product and what's the approximate freezer shelf life of the cells. Thank you.
Robert Burns: And then, this is David Chang, I'll take the question. In terms of the self-product, you know, frozen stability tends to be pretty, pretty, pretty long, you know, several years. First.
Robert Burns: What is being done is we carry out the stability test as time goes on and you know the stability is established by how long that we have done the stability test. So there will be an ongoing process and our expectation is that
Robert Burns: The inventory that we have under current stability testing strategy, will be sufficient to cover all the clinical studies that we are planning to do.
Thank you.
Thank you.
Speaker Change: And that concludes our question and answer session. I would like to turn the conference back over to management for any additional comments. Thanks.
Robert Burns: Well, thank you, operator, and thank you, everybody who participated in this call.
Speaker Change: I want to say that Allogene was built to challenge convention, and today that ambition is becoming reality. Without a pre, we are changing the playbook in large Giselle Informa. We are changing the playbook. We are changing the playbook in large Giselle Informa.
Speaker Change: With ALO 316, we are proving fellow tumors that we didn't reach up South Turkey, and with ALO 329, we are opening a bold new chapter in autoimmune disease. This is a new chapter in autoimmune disease.
Speaker Change: These are 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 work-class science, we intend to deliver. Thank you for your time, and we'll see you in the next video.
Thanks for joining us. Operator, you may now disconnect. Next.
Thank you.
Speaker Change: Thank you, ladies and gentlemen. Thank you for your participation in today's conference. This does conclude the program. You may now log off and disconnect. Everyone have a great day. Thank you.