Allogene Therapeutics Q4 2024 Earnings Call Transcript

Quartr
Provided by Quartr
March 13, 2025

There are 15 speakers on the call.

Operator

Hello. Thank you for standing by and welcome to Allogene Therapeutics Fourth Quarter and Full Year twenty twenty four Conference Call. After the speakers' presentation, there will be a question and answer session. Please be aware that today's conference call is being recorded. I would like to turn the call over to Christine Casciano, Chief Corporate Affairs and Brand Strategy Officer.

Operator

Ms. Casciano, 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 fourth quarter and full year of 2024. 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'm 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 forecast 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 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 displays any obligation to update these statements. I'll now turn the call over to David.

Speaker 2

Thank you, and welcome, everyone. It's a pleasure to be speaking with you today. At the start of 2024, we set forth a bold strategy that some viewed as merely words on PowerPoint with a distant horizon. A year later, we stand on the brink of a transformative year at Allogene. Pioneering Allogeneic CAR T therapy was never expected to be easy.

Speaker 2

It demands vision, rigorous science, relentless persistence and operational excellence. Today, all three of our key programs are approaching critical milestones, marking the tangible progress of our dedication. We enter 2025 stronger than ever with a differentiated pipeline and a clear path to shaping the future of allogeneic CAR T. Our programs in large B cell lymphoma, autoimmune disease and renal cell carcinoma are breaking new ground, reinforcing our commitment to making off the shelf cell therapy a new standard of care. Our pivotal Phase II ALPHA3 trial for SemaCell in first line consolidation large B cell lymphoma is widely considered to be groundbreaking.

Speaker 2

We are immensely proud of the innovation behind this trial. The enthusiasm from both community cancer centers and leading academic institutions has been truly energizing, and momentum continues to build with 40 sites now activated. We anticipate reaching a critical milestone with the lymphodepletion selection and fertility analysis around mid-twenty twenty five. This interim analysis will provide essential insight into whether our approach is on track to meet its objectives, providing a clear signal of progress when we select our lymphodepletion regimen. Beyond oncology, twenty twenty four also marks our official expansion into autoimmune disease with ALLO329, the first of its kind, CD19CD70 dual targeting allogeneic CAR T product candidate, powered by our proprietary DAGR technology.

Speaker 2

Earlier this year, we secured FDA clearance for our Phase one resolution basket trial in rheumatology, an important step towards delivering a scalable off the shelf CAR T options to the best number of patients who stand to benefit. The IND clearance for ALLO329 cements Allergen as a true innovator in the autoimmune disease space. We did not follow the crowd. We deliberately took the time to ensure our approach was differentiated, developing both an investigational product and trial specifically to address the unique challenges of autoimmune disease. ALLO-three twenty nine is designed to induce lasting remission by targeting both B cells and activated T cells.

Speaker 2

An equally important design feature is incorporation of our DAGR technology, which has the potential to reduce or even eliminate the need for lymphodepletion. If successful, this breakthrough could fundamentally change how CAR T therapy is deployed in autoimmune diseases. With the resolution trial slated to launch in mid-twenty twenty five and proof of concept data expected by year end, we believe ALLO-three 29 represents a new frontier in allogeneic cell therapy that will showcase the power of our platform to redefine treatment paradigms beyond oncology. In solid tumors, L-three sixteen is emerging as a promising and potentially groundbreaking asset in renal cell carcinoma. The Phase I data we presented last year underscores the potential of allogeneic CAR T therapy to drive meaningful responses in solid tumors, an area where cell therapies have historically faced immense challenges.

Speaker 2

With our regenerative medicine advanced therapy designation, ALLO-three sixteen has the potential to redefine treatment for advanced renal cell carcinoma, bringing a much needed innovation to patients with limited options. In mid-twenty twenty five, we plan to share an update from our Phase 1b cohort focusing on durability, a key factor in improving long term patient outcome. From a broader perspective, the momentum across our programs highlights the potential of allogeneic CAR T therapy to disrupt multiple disease areas. We aim to not just compete with autologous therapies, we are demonstrating that allogeneic approaches can surpass them in accessibility and scalability. Our bold pivot in 2024, coupled with our relentless execution affirms that we have the right team, science and strategy to make 2025 a breakthrough year for Allogene, one that defines the future of Allogeneic CAR T therapy.

Speaker 2

I would like to now hand the call over to Zack to provide further details on our clinical programs.

Speaker 3

Thank you, David. We take great pride in our clinical progress across our R and D organization and the company as a whole. All three of our cutting edge programs demonstrate significant promise reinforcing the strength of our science and execution. We are energized by the momentum in our pivotal semacel trial in first line consolidation LBCL, the upcoming launch of the resolution basket trial with ALLO-three 29 in rheumatology and the compelling data emerging from ALLO-three sixteen in advanced renal cell carcinoma. Let's start with the foundation of our programs.

Speaker 3

The field has questioned for years whether an allogeneic CAR T could deliver durable responses. With multiple patients with relapsedrefractory LBCL in ongoing complete remissions beyond four years, we now have proof that our products can achieve that. The Journal of Clinical Oncology's recent publication of our Phase I ALPHA2 trial results in relapsedrefractory large B cell lymphoma marks a defining moment for the field. These findings represent the most comprehensive allogeneic CAR T dataset to date. The study showed efficacy comparable to approved autologous CAR Ts with an overall response rate of fifty eight percent and a complete response rate of forty two percent across the study, increasing to sixty seven percent and fifty eight percent respectively with the pivotal study regimen.

Speaker 3

Importantly, treatment delivered exceptional durability with a median duration of response of twenty three point one months and median overall survival not reached in patients who attained CR. We also observed a potentially best in class safety profile with no cases of graft versus host disease, immune effector cell associated neurotoxicity syndrome or high grade cytokine release syndrome. The median time to treatment was just two days, significantly shorter than the weeks long wait times acquired for autologous CAR T. Moreover, these results provide compelling evidence supporting the use of CAR T therapy in patients with low disease burden. A growing body of research indicates that earlier intervention with CAR T when the disease burden is minimal can lead to improved safety and efficacy outcomes and this study reinforces that premise.

Speaker 3

Among patients with baseline tumor burden of less than 1,000 millimeters squared or normal LDH levels, a key biomarker of low disease activity, the complete response rates were one hundred percent and eighty two percent respectively. These findings strongly support semacel as a breakthrough therapeutic option for patients with minimal residual disease, which is the population studied in ALPHA3, the first randomized trial evaluating CAR T as first line consolidation therapy for MRD positive patients. With Semicell's one hundred percent CR rate in patients with low, but still radiographically evident disease burden in these earlier trials, ALPHA3 presents an unprecedented opportunity to both predict relapse and intervene before it occurs. If successful, ALPHA3 stands to upend the standard of care in first line LBCL, potentially marking the first significant advance to the treatment paradigm in the last twenty five years. Since the trial's launch in June, we have made steady progress.

Speaker 3

Today, we have successfully activated 40 of the planned approximately 50 sites with roughly a fiftyfifty split between community cancer centers and academia, and we are progressing towards the first key milestone in ALPHA-three trial, the lymphodepletion regimen selection anticipated around mid-twenty twenty five. Beyond signaling progress in accrual, the lymphodepletion selection step is paired with a futility analysis and thus our decision to proceed will be a critical indicator that the trial is on track to meet its objectives based on early data. Moreover, this milestone will help map the registrational path forward further solidifying our confidence in SemaCell's potential to redefine the standard of care. Due to the seamless pivotal design, these early patients results count towards the pivotal analysis and therefore, we will not be releasing detailed efficacy or safety outcomes to protect trial integrity. Beyond LD selection, we plan to conduct an interim EFS analysis, which will be overseen by the independent Data Safety Monitoring Board in the first half of twenty twenty six.

Speaker 3

The primary EFS analysis data readout is expected around year end twenty twenty six with a potential BLA submission in 2027. None of this would be possible without the great partnership of Foresight Diagnostics and their ultra sensitive ctDNA based CLARITY assay powered by Phase C. For this reason, we expanded our strategic collaboration with Foresight to support the development of their MRV assay as a companion diagnostic in The EU, UK, Canada and Australia to support Allogene's clinical development of Semicell. Shifting gears to autoimmune diseases, in January 2025, the FDA cleared the IND for the Phase I Resolution Basket trial, a first of its kind study evaluating ALLO329 in systemic lupus erythematosus, lupus nephritis, idiopathic inflammatory myopathies and systemic sclerosis. This true basket design brings significant operational efficiencies, allowing enrollment access to a broad patient pool with a single IRB approval.

Speaker 3

This is one of several differentiating factors that may prove advantageous in this competitive space. The strategy behind ALLO-three twenty nine stems from two key observations. First, autologous CAR T data suggests that short term CAR T persistence is sufficient to reset the immune system in autoimmune diseases contrasting with the months to even years long persistence needed in oncology. Since B cell depletion lasts around one hundred days in autologous studies, allogeneic CAR T's natural two to four month persistence makes it uniquely suited for autoimmune therapy. Second, data from our Phase I ALLO-three 16 program in kidney cancer demonstrated that our DAGR technology intrinsically enhances cell expansion and persistence, allowing us to significantly reduce intensity of lymphodepletion without sacrificing efficacy.

Speaker 3

These insights shaped ALLO-three 29, which includes the DAGR technology and is intended to enable reduction or even elimination of lymphodepletion, a major differentiator in autoimmune treatment. The RESOLUTION trial will immediately test the requirement for lymphodepletion in parallel cell dose escalation pathways. In one, we will use a single infusion of cyclophosphamide at a dose used in rheumatology and in the other, a CAR T only arm with no lymphodepletion relying entirely on the DAGR effect. This trial is set to launch mid year with proof of concept data expected around year end. With extensive preclinical validation, published data and an optimized design, ALLO-three 29 is positioned to be the most rigorously designed allogeneic CAR T program for autoimmune disease to date.

Speaker 3

Beyond rheumatology, its potential extends to nephrology, neurology, hematology and even inflammatory bowel disease, paving the way for a new era of CAR T therapy in immune driven conditions. Last quarter, I highlighted ALLO-three sixteen and its remarkable potential following data that showcased encouraging responses from a single infusion with an impressive fifty percent best overall response rate and a thirty three percent confirmed response rate in heavily pretreated metastatic kidney cancer patients whose tumors expressed high levels of CD70. Given that update, I'll keep it brief today with just a reminder of the next steps for this promising program. We have completed enrollment in the Phase 1b expansion cohort, which is assessing safety, efficacy and durability of ALLO-three sixteen at dose level two or 80 million CAR T cells following standard lymphodepletion with fludarabine and cyclophosphamide. As we continue to evaluate outcomes, we will determine the best path forward, including the potential to pursue a strategic partnership.

Speaker 3

We expect to share data from this cohort in mid-twenty twenty five. I'll now turn the call over to Jeff.

Speaker 4

Thank you, Zack. I'll focus my remarks on our financials. Our financial position is strong and we continue to operate with capital discipline, ensuring we are well positioned to advance our pipeline and pursue our strategic objectives. As of 12/31/2024, we had $373,100,000 in cash, cash equivalents and investments with our cash runway extending into the second half of twenty twenty six. Research and development expenses for Q4 twenty twenty four were $45,000,000 including $5,600,000 in non cash stock based compensation expense.

Speaker 4

For the full year of 2024, R and D expenses totaled $192,300,000 including $20,400,000 in non cash stock based compensation. General and administrative expenses for Q4 twenty twenty four were $15,500,000 including $7,300,000 in non cash stock based compensation. For the full year, G and A expenses were $65,200,000 including $31,300,000 in non cash stock based compensation. Net loss for Q4 twenty twenty four was $59,900,000 or $0.28 per share, including $12,900,000 in non cash stock based compensation. For the full year, net loss was $257,600,000 or $1.32 per share, including $51,700,000 in non cash stock based compensation and $15,700,000 in non cash impairment of long lived asset expense.

Speaker 4

Turning to guidance for 2025, we expect a cash burn of approximately $170,000,000 We expect full year 2025 GAAP operating expenses to be approximately $250,000,000 which includes an estimated non cash stock based compensation expense of approximately $50,000,000 This guidance excludes any impact from potential business development activities. We'll now open the call for questions.

Operator

Thank you. Our first question comes from Tyler Van Buren with TD Cowen. You may proceed.

Speaker 5

Hey guys, thanks very much and congratulations on all the progress. My question was just following up on the recent JCO publication that you highlighted and thinking about the read through as to the ongoing ALPHA-three trial. How do patients with low disease burden in the publication compare to those being enrolled in ALPHA-three as we think about the high complete response rate holding up in ALPHA-three?

Speaker 2

Hi, Tyler. Excellent question. I think one thing that we highlighted in our JCO paper and this is in fact something that we have been saying for some time based on what has been seen in OTHALA's CAR T therapies. When you look across patients who have been treated with CAR T, I think this extends not just CD19, but with other BCMA or other antigen targeted CAR T and heme malignancies. There is a very strong correlation of likelihood of response as well as likelihood of experiencing adverse events, serious adverse events.

Speaker 2

I mean, actually, it's an inverse relationship in the latter case. When the disease volume goes down, the likelihood of response is much higher. At the same time, the probability of having a serious adverse event goes down. That has been seen numerous times and there are many publications on that. And essentially in the JCL paper, we were showing that essentially the same falls true for the allogeneic CAR T.

Speaker 2

They're probably not that surprising. And I think this really bodes well for what we're doing, not only in the ARFA-three study, but also as we think forward into the autoimmune program with ALLO329. Specifically about your question, in terms of estimating the disease volume MRD compared to patient who's studying the front line study I'm sorry, second line study. There is some information that we have done together with Foresight Diagnostics. MRD positivity is about 200 fold less disease volume than patients who are presenting with disease for the start of the second line treatment.

Speaker 2

Your particular question about how that compares with low volume, the two categories of low disease volume that we have published in JCL, LVH or the tumor measurement. I would more or less extrapolate to about the same degree of lower disease volume as we have previously reported together with Foresight in the second line setting versus MR deposit.

Operator

Thank you. Our next question comes from Michael Yee with Jefferies. You may proceed.

Speaker 6

Hey, good afternoon. Congrats on all the progress. As we are thinking about the mid-twenty five futility and lymphodepletion decision, I wanted to get your affirmation that you believe that six forty seven is extremely likely to not be needed and that should be the general Wall Street expectation and I believe that would be a positive for a number of reasons. And then as we get to the first half of twenty twenty six, which would be around the corner, it does say that there's an interim DSMB efficacy analysis. What is the criteria, number of events or is there a very high P value bar on that?

Speaker 6

What are you expecting or what should we expect at that interim? Thank

Speaker 2

you. Hi, Mike. I'm going to defer your questions to Zach. Zach, can you take those two questions?

Speaker 3

Of course. Thanks, Mike, for the great question. So our opinion on the lymphodepletion selection is sort of agnostic. I think you raised a fair point that not needing 6 40 7 brings some attractive attributes like it would be simpler for us, we're registering one entity instead of two. It certainly would be cheaper for us to do it that way.

Speaker 3

However, we see requiring six forty seven is actually potentially beneficial as well because that's part of our proprietary regimen. So, it would help kind of protect our status here as the only therapy that is optional in this particular clinical setting. So, we have designed this clinical trial to give us a solid answer to that question, is six forty seven needed in this unique clinical trial or is it not? And I think we can work with either independently, both has upside for us. And the sorry, Mike, will you repeat the second question?

Speaker 3

I've forgotten that one.

Speaker 6

Yes, right around the corner That's right. Within twelve months or so is the interim by DSMB. Well, what is the criteria? Is it a high bar because you don't want to spend alpha there? But obviously investors have had great discussions with you about how the drug is clearly going to be working here.

Speaker 6

You can definitely have a chance of hitting there. Thank you.

Speaker 3

Yes. So we haven't disclosed a lot of the specifics around the nature of that analysis, such as some of the specifics that you're requesting, except to say that it is a formal efficacy test where we will be testing the hypothesis with the primary endpoint of event free survival. There will be some minimal alpha spend. So it is quite possible just given the way this study is designed that we could end up with a statistically significant finding there, which would of course allow us to initiate conversations with the FDA, begin to kind of move more briskly across the other elements that need to fall into place to launch the program and in the coming months after that. So we are looking forward to that analysis.

Speaker 3

And in either case, whether it meets statistical significance or it doesn't, we look towards that as a very significant sort of milestone in the delivery of this program.

Speaker 6

Thank you.

Operator

Thank you. Our next question comes from Salveen Richter with Goldman Sachs. You may proceed.

Speaker 7

Hey, this is Mark on for Salveen. Thanks for taking our question. For ALLO-three '29 and the trial starting soon in autoimmune disease, what data are you looking to show by year end to demonstrate proof of concept? And maybe more importantly, since there are many CD19 players and also allogeneic players showing data this year. How do you think your approach is differentiated and could your year end data support said differentiation?

Speaker 2

Thanks. Hi, Mark. This is Dave Chang. Let me take on that question. So three to nine, we have cleared IND and we expect to initiate the clinical study mid-twenty twenty five.

Speaker 2

And we have been guiding towards proof of concept data towards the year end. The number of patients that we expect to treat in 2025, because this is dose escalation Phase one study, will be somewhat limited, but it will be handful. And what we are looking for is biomarker based proof of concept. One, do allogeneic ALLO329, do they expand well? I think those are very important information.

Speaker 2

And second, do we achieve the B cell depletion while also allowing some of the B cell recovery to occur? These are some of the important information that will lead to the proof of concept. And also in some of the patients that we treat, we expect them to have auto antibodies and the measurement of auto antibodies before and after the treatment, that could also give a lot of insight into what the program is doing. In terms of differentiation of L329 to many other programs that are currently in the autoimmune space, I think the key is that one, this is an allogeneic program. And two, this has ability to not only deplete the B cells, but also activated T cells, which contributes to the overall pathogenesis of autoimmune disorders.

Speaker 2

How the latter would translate? I think we will have to see the clinical data, but possibilities are being able to address the T cells can allow us to go to indications that CD19 B cell targeting therapies may not necessarily be sufficient. And another potential benefit of targeting T cells is that the remission could be much longer because you are eliminating not just T cells, but also T cells.

Speaker 8

Awesome. Thank you.

Operator

Thank you. Our next question comes from Brian Chien with JPMorgan. You may proceed.

Speaker 9

Hey guys. Thanks for taking our questions this afternoon. David, I'm just curious if you can provide a little bit more comment around your latest thinking around incorporating potentially other milder lymphodepleting agent or even completely removing the standard CyFlu that you're using. Any color on timeline? And what is really the fastest and the best way to kind of sort that out?

Speaker 9

Thank you.

Speaker 2

Yes. Brian, excellent question. These are the things that we hope to address in the Phase one study. In the planned study, first of all, the lymphodepletion that we will be deploying is a milder lymphodepletion we have taken out fludarabine. So one cohort will be treated with acaclofosamide alone as a lymphodepletion.

Speaker 2

And the second one, we have also clarified when we announced the clearance of IND is that in parallel, there will be second cohort where we will be testing without any lymphodepletion. So a little bit to your question as well to the previous question about Mark from Mark is really the Phase one study already is built in to address the key questions about 03/29, whether it can achieve the objective with milder, which will be a fantastic news or even without any lymphodepletion, which will be phenomenal for this program.

Operator

Thank you. Our next question comes from Sami Kornblin with William Blair. You may proceed.

Speaker 10

Hey there. Congrats on making the progress this quarter. Thanks for taking my questions. I was curious what increase or difference in event free survival OPHA3 is powered to show. And then I noticed in your 10 ks that it said that if both treatment arms look better than the control of the futility analysis, but they don't look any different than each other that additional patients could be enrolled and analyzed.

Speaker 10

So I guess what kind of difference are you looking to see between the two treatment arms? And if they do look similar, would you pursue the lymphodepletion arm without six forty seven? Thank you.

Speaker 2

Yes. Sami, I mean, the question about the powering of the ALPHA3 study, I mean, the primary endpoint is event free survival. We haven't gone into the specifics about the powering of the study other than saying with the targeted about 110 patients each on for comparison, this study is very well powered. And this also goes back to the earlier question around from Mike about what could be possible at the interim analysis, which will happen early twenty twenty six. Yes, we are spending some alpha and obviously, we believe that there is some possibility, which may be not so small that the statistical boundary may have crossed at the time.

Speaker 2

And frankly, if you look at what has happened with the CAR T studies in the second line study, whether it's the ESKATA or BRIANZA study, the sample size, number of patients that were treated in the second line study, which was comparing CAR T with the active treatment, it's around two sixty to some mid-three hundred, not so dissimilar. So those studies obviously will show the statistical significance in the mid year. So I think that is probably some good reference to think about how APHA-three study may have been powered. And your second question about what we have disclosed in the 10 K, we have provided a little more guidance about how many number of patients that we'll be looking at as we start looking at the futility as well as selecting the lipo depletion. Here, obviously, if we don't see any difference, there are possibilities as we may want to have some more patients to see whether there are differences more significant or not.

Speaker 2

Another possibility is that at the time of reviewing about 36 patient data, that may provide sufficient information for us to make the lymphodepletion. We will get there and this will be very much data driven. So probably it's best that we wait to that time point rather than speculating too much.

Speaker 1

Got it. Thank you.

Operator

Thank you. Our next question comes from Jack Allen with Baird. You may proceed.

Speaker 11

Welcome. Thank you so much for taking the questions and congrats on the progress. I just wanted to ask about the pituit analysis as well. How should we be thinking about the futility analysis as it relates to the comparison? Is it a comparison against the control arm here or is it against some sort of hurdle rate?

Speaker 11

And then on what metrics will you be looking at to evaluate futility? It will be MRD conversion, response rates or any early survival data? Thanks so much.

Speaker 2

Yes, Jack. Let me just take this question. We got asked about the futility question. There isn't anything unique about the futility analysis that we are doing. This is a very standard thing that many in a Phase III study, sometimes even Phase II studies will be doing.

Speaker 2

What gets looked at in the futility analysis, really the totality of the data. You can look at the safety. Obviously, we want the safety to be tracking close to our expectation based on what we have seen in the APHA3 study. And there is a significant imbalance in the safety between the observation control arm versus two treatment arms. And then the second one is the sort of the signs of efficacy.

Speaker 2

And here, we will be relying primarily on the MRD conversion rate. So every patients who get enrolled in ARFA-three study starts with MRD positive, both the control as well as the two treatment arms using different lymphodepletion. The expectation is MRD conversion will be heavily upgrading more, it's going to be more in the treatment arm compared to the observation. So that will be the essentially the futility that we'll be looking for. Then afterwards, once that futility has been crossed, we'll be looking at the two treatment arm, two lymphodepletion arms to see which one is better.

Speaker 11

It. Thanks so much for the color.

Operator

Thank you. Our next question comes from Byron Amin with Piper Sandler. You may proceed.

Speaker 12

Yes. Hi, guys. Thanks for taking my question. I think for the ALPHA-three, your prior guide stated that patient enrollment would complete by first half of twenty twenty six. So I just want to see if you're continuing to track towards that timeline.

Speaker 12

And then I guess second question is, I think you mentioned that the split in the trial is fifty-fifty between community versus academic in terms of sites. How about the patient split? Is that fifty-fifty as well?

Speaker 2

Biren, in terms of the overall trial guidance, we are now focusing more on the data reader, which has not changed. And obviously, your particular question around trial completion, I think we are more or less tracking around that time. And obviously, as we progress with the study, we'll provide more information. With respect to your second question, Can you just repeat the second question?

Speaker 12

Yes. I think you mentioned in terms of the trial split, the site split is fifty-fifty across the 40 sites that you've activated between community and academic.

Speaker 2

Yes. And so

Speaker 12

I want to understand

Speaker 8

if the

Speaker 12

patient looks similar as well.

Speaker 2

Yes. Let me pass that question to Zach to provide more details on in terms of the site distribution across community versus academic centers.

Speaker 3

Yes. Thanks, David, and thanks, Biren, for the question. Yes, you're correct that it's about fiftyfifty split right now with about four fifths of the sites activated community versus academic. As far as the patients coming in, what I can say is that we haven't seen a heavy skew in one direction or the other. I can't say it's exactly fiftyfifty, but what I can say is that we are seeing robust activity in both the community centers as well as the academic centers.

Speaker 12

Great. Thank you.

Operator

Thank you. Our next question comes from John Newman with Canaccord Genuity. You may proceed.

Speaker 5

Hi guys. Thanks for taking my question. Just wondered on the initial data for 03/29 at year end 2025, just curious if you know how much follow-up you might have if you would be able to look at one month or maybe three? And then also given the mechanism of action for 03/29,

Speaker 2

is there a way that you can look at not just the B cell depletion,

Speaker 5

but also potentially depletion of the active T cells? Thanks.

Speaker 2

John, great question. It's something that we constantly talk about internally. Let me pass off to Zack to answer the questions about the length of follow-up that we may have and what else we're going to be looking at in the biomarker analysis. Yes. So thanks, John.

Speaker 3

So we haven't said exactly how much follow-up we expect to have and we have said that with the trial starting middle of this year and us obviously moving as quickly as we can, we should have a handful of patients treated hopefully by the end of the year and a little bit of follow-up. I mean, what we've guided towards in terms of proof of concept is, as David pointed out earlier, the biomarker data, so B cell depletion as well as expansion of the CAR T cells. And we'll have some early safety results too. So we can gather that information in relative short order in a clinical trial. We won't really have a significant read on durable efficacy, of course, by the end of this year.

Speaker 3

Diving into your second question on the specific analyses that we plan to conduct, so obviously, B cells is a must have, but the T cells, as we have shown in the three sixteen program, is going to be an area of focus as well. And what I think we've elegantly shown, such as in the SITC data just a few months ago, is that we can really parse out the CD70 positive versus the CD70 negative cells in the patients. And really that is what has given us the foundation to that has validated the DAGR effect in patients. So we'll be doing very similar analyses in 03/29 and seeing whether we are seeing that evidence of a strong dagger effect in these patients.

Speaker 5

Okay, great. Thank you.

Operator

Thank you. Our next question comes from Matt Suttag. Good morning with Truist. You may proceed.

Speaker 8

Hi guys. Thanks for taking my questions and appreciate all the color today. I want to follow-up John's excellent question on the resolution study. It's great to see that you guys are aiming to explore the lymph depletion free strategy as well here. I want to ask you this, how much follow-up do you need to answer that question?

Speaker 8

And I ask because just in some of these indications they're going after, the KOLs out there like to see maybe a treatment benefit up to six months or even a year. Do you think you'll need to do that to get all the way up to then to really answer that question of whether or not you can go with the lymphodepletion fee strategy? And then second quick follow-up on the JCO publication, all the durable responses were CRs and it also goes further to say that all six patients with low disease burden had CRs. So I'd like to confirm, are those the six patients that are the ones that are still in response on the swimmer at the data cutoff on that paper? Thanks.

Speaker 2

Yes, Vikas, two questions. Let me take the three twenty nine resolution question about whether we need to follow the patient for longer. Definitely without question, we will be following these patients longer than the initial biomarker data analysis. So the way we see it is a biomarker, especially T cell depletion and cell expansion, autoantibody, titer changes. I think these are very great telltale signs around whether the treatment is three twenty nine is behaving as we have expected.

Speaker 2

And obviously, as we follow these patients, we will get more information about the clinical outcome, including if some of these patients going to complete remission, how long that may last. I mean those are much longer follow-up and they will not be the part of the initial data release that we are projecting year end. The second question, I'll pass off to Zack to respond. Zack?

Speaker 3

Yes. Thanks, Asthika. So the first thing to kind of keep in mind is, as you pointed out in your question is most important outcome after any treatment at all, whether it's CAR T cells or anything else, is that you achieve a complete remission. That is obviously the number one thing, because if you don't get to a complete remission, your chance of durable cure is zero. So that's the first thing to keep in mind.

Speaker 3

What we showed in our subgroup analysis is that if you had low disease burden as assessed by either the tumor measurements or by the serum LDH, you had an extremely high chance of achieving that must have clinical scenario of a complete remission. That said, we want to also tout that the SemaCell product itself is a very potent product. Obviously, it's very active as the JCO paper indicated. And we actually had plenty of patients that were had bulky disease that achieved durable CRs as well. So it was a little bit of mixing and matching.

Operator

Thank you. Our next question comes from Matthew Beagle with Oppenheimer. You may proceed.

Speaker 9

Hey guys, thanks for

Speaker 13

the question. I'll ask another one on resolution, but maybe in a slightly different way, which is hypothetically, how much efficacy are you, I guess, potentially willing to leave on the table to get away with no lympho conditioning, I. E, is no lympho conditioning really a game changer? Or is it just a nice to have in your opinion? Thanks.

Speaker 2

Yes. Matthew, excellent question. You are asking things that are highly debated internally. I mean, probably the best way that I can sort of describe is lymphodepletion is a potential barrier. And go lower I mean, if you can lower the lymphodepletion, that's a big plus.

Speaker 2

And if you can eliminate, that's really a big, big game changer. But frankly, probably the best way to think about it is when it doesn't require it doesn't have the burden of lymphodepletion, it can be used more widely. So it really creates the potential to treat not only autoimmune disorders with a high severity, but also moderate severity. So it gives a lot more opportunity to address different patients. So, yes, we would love to have no lymphodepletion, but I think even just lowering the lymphodepletion would be a significant win for the three twenty nine program.

Speaker 5

Appreciate it.

Operator

Thank you. Our next question comes from Luca Icy with RBC Capital Markets. You may proceed.

Speaker 9

Hey, guys. This is Shelby on for Luca and thanks for taking the question. On ALPHA3, it's our understanding that there is an option for inpatient or outpatient treatment. Is that decision left up to the investigator? And how should we think about the mix of patients who will be treated outpatient versus inpatient?

Speaker 9

Any color there, much appreciated. Thanks.

Speaker 2

Yes. Shelby, I'm going to ask Zach to respond to your question. Zach?

Speaker 3

Yes. Thanks, David and Shelby. So indeed, there is no requirement at all for inpatient either LD or cell administration. It is entirely up to the investigator on a case by case basis. I will say that, we are seeing as we've seen for a long time in our semacel programs, even in the alpha and alpha two, we are seeing a significant number of these patients being treated fully as an outpatient.

Speaker 3

And of course, that is the vision part of the vision for this product is that it's going to be easy to administer in the clinical settings where these patients receive frontline care. As for sort of specific characteristics that would lead to a patient being treated inpatient versus outpatient, there's a host of them, I won't go into them now, but one of the great benefits of the ALPHA-three study is that all of these patients are going to be in remission when they receive their semacel and their lymphodepletion. And as David pointed out earlier in the call, patients with low disease burden tend to have better safety outcomes than those with high disease burden. So on balance, we would expect significantly greater fraction of these patients over the duration of the study to be managed as fully as outpatients and that is our expectation.

Speaker 2

Yes. And also if I can add one color to that response, Shelby. I mean, I think the important thing is that in our three study, we do not require hospitalization. And in that way, in essence, what that's doing is, this trial is just like any other trial. And whether physician does with that information, whether they decide to treat as a fully outpatient or maybe put them in the hospital for a day or two.

Speaker 2

I mean, that's essentially how the practice is done in not just in the cell therapy, but in any other cancer treatment. So it's really giving the patient and the physicians the option on how they want to receive the investigational therapy in the ALPHA-three study.

Operator

Thank you. Our next question comes from Samantha Simenka with Citi. You may proceed.

Speaker 14

Hi, good afternoon. Thanks very much for taking the question. Some of your autologous CAR T counterparts have spoken about a push to expand into large community oncology centers that could potentially overlap with your alpha three trial sites. So I'm wondering to what extent are you seeing this infrastructure being built at the community centers you interact with? How much of this groundwork do you think could be in place by the time you potentially launch them as well?

Speaker 14

How are you thinking about your ability to leverage this infrastructure for the launch? Thanks very much.

Speaker 2

Samantha, excellent question. I think the effort not just by us, but also in the entire CAR T community to move into the sort of community based cancer centers, I think that's just going to expand and expand the usage of CAR T. I mean, that's a very important aspect of any product launch and product life cycle management. I think in many ways, here is where the allogeneic CAR T really plays favorably. I mean, the not having the logistical challenge, just being able to ship the product when the patient needs the treatment.

Speaker 2

And also in our case, as we are learning, as we improve the manufacturing, the scalability of the manufacturing, all these things are playing in our favor. So as the effort from the Autonomous CAR T companies to expand their use into the community cancer centers, We see that as a positive thing for the field and we also see that as a positive thing for what we are doing with the ALPHA-three study.

Operator

Thank you. Our next question comes from Ben Burnett with Stifel. You may proceed.

Speaker 1

Hi, this is Carolina Ivanoventas on for Ben. Thank you for taking our questions. First, on the interim analysis of SemaCell in mid-twenty twenty five, can you remind us when you are measuring the MRD conversion? Is it at one month post SemaCell infusion or later? And I have a follow-up.

Speaker 2

Yes. We're trying to limit the questions to one. Zach, you want to take the question about the timing of the America test?

Speaker 3

Yes. Thanks, Catalina. We have not disclosed exactly the timing of that draw. And as David pointed out earlier, of course, there'll be other elements that we're assessing to make that lymphodepletion decision in addition to the MRD conversion.

Speaker 1

Okay, understood. Thank you.

Operator

Thank you. Our next question comes from Laura Prendergast with Raymond James. You may proceed.

Speaker 9

Hey guys. Can you elaborate a bit more on the registrational path for the Foresight MRD test and how it relates to the registrational path for semacel and 1L lymphoma? Thanks.

Speaker 2

Hey, Zach, do you want to take that question?

Speaker 3

Yes, that will be an easy one. Thanks, Laura. We the plan has been all along to have a concurrent launch of these products at the time of the FDA approval. The specifics around the path to registration of the MRD test, though, I would refer you to the Foresight management.

Speaker 9

But you don't foresee it being an issue at all with getting semisol approved in first line? No. Got it. Thanks.

Operator

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

Speaker 2

All right. Thank you. I just want to reiterate, Allergan entered 2024 with a bold strategy. And today, we stand on the brink of a transformative year. With three pioneering programs, each approaching critical milestones, we are proving that allogeneic CAR T has the potential to redefine patient care.

Speaker 2

So thank you for your ongoing belief in allogene and the field of cell therapy. Operator, you may now disconnect.

Operator

Thank you. Ladies and gentlemen, thank you for your participation in today's conference. This does conclude the program and you may now log off and disconnect.

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Earnings Conference Call
Allogene Therapeutics Q4 2024
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