Q4 2023 Allogene Therapeutics Inc Earnings Call

Participants

Christine Cassiano; EVP, Chief Corporate Affairs and Brand Strategy Officer; Allogene Therapeutics Inc

David Chang; President, Chief Executive Officer, Co-Founder, Director; Allogene Therapeutics Inc

Zachary Roberts; EVP, Research & Development, Chief Medical Officer; Allogene Therapeutics Inc

Geoff Parker; EVP, CFO; Allogene Therapeutics Inc

Tyler Van Buren; Analyst; Cowen & Co., LLC

Salveen Richter; Analyst; Goldman Sachs & Company, Inc

Brian Cheng; Analyst; J.P. Morgan Securities LLC

Jack Allen; Analyst; Robert W. Baird & Co., Inc

John Newman; Analyst; Canaccord Genuity LLC

Kelsey Goodwin; Analyst; Guggenheim Securities, LLC

Reni Benjamin; Analyst; JMP Securities

Kalpit Patel Patel; Analyst; B. Riley Securities, Inc

Luca Issi; Analyst; RBC Capital Markets Wealth Management

Laura Prendergast; Analyst; Raymond James & Associates, Inc

William Pickering; Analyst; Sanford C. Bernstein & Co., L.L.C.

Presentation

Operator

Thank you for standing by, and welcome to Allogene Therapeutics Fourth Quarter and Full Year 2023 conference call. (Operator Instructions) Please be aware that today's call is being recorded. I'd now like to turn the call over to Christine Cassiano, Chief Corporate Affairs and Brand Strategy Officer. Ms. Cassiano, please go ahead.

Christine Cassiano

Thank you, operator, and welcome to offer and showing a call after the market closed today, Allogene issued a press release that provides a business update and financial results for the fourth quarter and full year 2023. This press release and today's webcast are available on our website. Following our prepared remarks, we will host a Q&A session. We ask you to limit your questions to one per person as we will keep this call to an hour and do our best to get to as many questions as possible. Joining me today are Dr. David Chang, President and Chief Executive Officer; Dr. 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 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 for safety and efficacy of our product candidates, and 2224 financial guidance among other things. These forward looking statements are based on current information, assumptions and expectations that are subject to change. A description of potential risks can be found in our press release and latest SEC disclosure documents for a question not to place undue reliance on these forward-looking statements, and Allergan disclaims any obligation to update these statements. I'll now turn the call over to David.

David Chang

Thank you, Christine. Thank you for all who have joined our call today. Rather than looking back, which is the norm for this type of coal, I would like to take the opportunity to look ahead. We have recently returned from an investor conference in Boston and well beyond thrilled to fill or the renewed enthusiasm for biotech and even more so a resurgence in cell therapy. I would argue that this is also true for Allergan segments seemingly shared by many of our investors following the payment we announced at the beginning of 2024 from our innovative offer three trial, which is designed to embed Fermacell as part of a curative first-line regimen for pain patients with large B cell lymphoma to specifically crea ting a CAR T that could meet the unique needs of patients with autoimmune disease and possibly reduce reliance on lymphodepletion. Our development approach focuses on the distinctive attributes of an off-the-shelf off.
While our CAR T programs, we are no longer developing CAR T using an outdated playbook. Now that we have established the viability of our allogeneic platform product can be developed using a fresh approach created for what we do, both in design of our trial and design of our cost structure to meet the current and future needs of pesos and dramatically expand opportunity. But three, which based on feedback from investors and doctors is perhaps one of the greatest example of the role on allogenic CAR-T can play in this resurgence for cell therapy. This is the first pivotal trial for frontline consolidation in large B cell lymphoma with a goal all of improving cure rates.
There was significant insight gathering work and discussion with the FDA in 2023 to inform and finalize offer three. When we revealed that trial in January, there was an acknowledgment almost right away that this groundbreaking trial creates the potential to leapfrog all other CAR T and embed ourselves in first line treatment. Equally important is the innovative concept of treating minimum residual disease or MRD, together with the benefit of drug in a vial, could open the door to make allogenic CAR-T available in community based cancer centers who are most earlier line patients are treated. The more we have talked about offer three deeper understanding.
This trial design is something truly unique, a rare opportunity in oncology to do a randomized trial against observation and the prospect of becoming a new standard of care in the first line setting, based on the addressable market, just in the US, the revenue potential could be upwards of $3 billion and could easily double went expanded ex US. This type of app is showing only presents itself when you servicer on patients and endeavor to be curative. Our second most as program by investor asked, Alpha three is out of three to nine in autoimmune disease or AID. enthusiasm for CAR T AID. is palpable.
However, we have chosen not to rush into the already crowded field with an undifferentiated approach. The future results of that could mean an uphill battle in trial enrollment or was it commercialization. Instead, we are applying our deep and hard earned experienced specifically design. Our view are targeting CAR-T 2.0 for autoimmune disease. Our design is centered on both scalability and reducing or eliminating lymphodepletion, which we believe is apps LIG critical for rapid clinical development and future commercial success. We expect to be in clinic with our three to nine in a Phase one trial in early 2025. Our next to Paul program off the lean into attributes of allogeneic CAR T.
Our new offer two cohort foot center ourselves in chronic lymphocytic leukemia or CLL, aims to address the growing unmet need among patients whose disease has controlled by DTK and or BCL2 inhibitors. Relapsed refractory CLL in the second and third line setting represents a commercially attractive opportunity with revenue potential in the $3 billion range in the US. We believe an allogenic CAR-T product is particularly well-suited to overcome. In limitation for itself, fitness is unknown barrier to efficacy.
New approvals could reopen the door of interest in CLL, and we look to charge through it with our program. Our ongoing TRAVERS trial tackles one of the hardest industry challenges flood, one, we are willing to undertake solid tumors. ALLO-316 in renal cell carcinoma leverages our dagger technology to optimize CAR T cell expansion and persistence to maximize the potential of an allo CAR T in the second quarter with plans to publish what we believed to be fundamental discovery that algorithm that may mitigate the treatment associated hyper inflammatory response without compromising the CAR-T functions needed to eradicate solid tumor. A more comprehensive update from the TRAVERSE trial is planned for year end 2024. Now I'd like to turn the call over to Zach to address some of the more commonly asked questions about our programs.

Zachary Roberts

Thank you, David. As I'm sure you can tell, we are all very excited about our new strategy and thrilled that investors and investigators Allied share that enthusiasm. I'll start with CLL because that gets a little less attention and out of three, although it has the potential to pack a powerful punch. It's ironic that complete remissions in relapse refractory CLL ignited the CAR T fields many years ago. But that excitement, Wayne, for the limitations we stated new approvals could offer a much needed alternative for these patients. There remains a growing need for effective treatment post be TKIs and Bcl two inhibitor therapies region, autologous CD19 CAR T data has been a positive step for patients with relapsed refractory CLL, but there is still room for improvement.
Durable responses in relapsed-refractory CLL is likely hindered by an unfortunate reality that T cell dysfunction and high circulating tumor burden makes manufacturing of highly after T cells difficult. So a strong scientific rationale to believe that an allo CAR T product derived from healthy donor cells could create a clinically meaningful advance for these late-stage patients for the one-time dose and simpler administration and logistics for new Phase one, Alpha two cohort will include 12 patients treated with Fermacell. This study driven by investigator enthusiasm is now enrolling patients, and we plan to have initial data at the end of this year.
I'll now talk about ALLO-329 in autoimmune disease, our net content advance, we believe the approach we are taking to reduce or even eliminate the need for standard lymphodepletion will be critical to meet the unique requirements for these patients. The risk tolerance of these patients is very different than those with cancer in large part because of patient demographics, wide availability of effective therapies and rheumatologists, general lack of experience with chemotherapy, local for Reese's procedures and cell therapies, our wholly owned next-generation site-specific integration base, dual targeting CD19 CAR TD70 allo CAR T is designed to reduce or eliminate the need for standard chemotherapy for targeting CD19 positive T cells and CD70 positive activated T cells, both of which play a role in autoimmune disorders. We haven't invested in this highly differentiated dual targeting approach to set us apart from the pack and position us for long-term success.
All current CAR T programs in AID. are targeting CD19 and therefore solely addressing the decel component. We believe that introducing CD70 will allow the elimination of both pathogenic BN. T cells that underlie autoimmunity, thereby potentially increasing effectiveness in diseases with direct or indirect T cell involvement, possibly allowing us to extend beyond indications in which the strict CD19 targeting has demonstrated clinical benefit.
Of course, the ability to manufacture hundreds of off-the-shelf CAR T doses from a single healthy donor Lucas, Reese's could provide an additional competitive advantage during clinical trial execution and with much more readily meet the potentially enormous commercial demand. Initiation of this Phase 1 trial was ALLO-329 is expected in early 2025. We are very excited to have partnered with Harbor biotechnologies for use of their proprietary crisper gene editing technology to support our overarching next-generation allo CAR-T platform in autoimmune disease.
By I'll make them mistake. This was a year of hard work for bringing this novel trial to live with the broader Allogene team. Our advisory boards and potential investigators, both comprised of academic KOLs and community oncologists alike and securing the support of the FDA is already one of the highlights of my career. The elegant design of this innovative trials and the AHA that comes with it is likely why we get asked why hasn't anyone tried this before?
It simply wasn't possible until now to run a study like alpha three, we needed to things to come together, a highly accurate MRD assay and a one-time powerful treatment that could be administered immediately. We believe we now have the right combination. The design of the alpha first line consolidation trial builds upon the results demonstrated in the Phase one alpha two trial and leverage is there an investigational cutting edge diagnostic tests developed by foresight diagnostics to identify patients who have minimal residual disease at the completion of frontline chemo immunotherapy for treatment with Fermacell, approximately one-third of LBCL patients who initially respond to R-CHOP will relapse.
Unfortunately, until recently, there has been no way to know which patients could go on to never experienced disease recurrence and which would have their cancer relapse standard of care after frontline treatment has for decades been just simply watch and wait wait for this disease to relapse. Alpha three takes advantage of stem cell as a onetime off the shelf treatment can be administered immediately upon discovery of MRD following six cycles of R-CHOP, positioning it to become the standard seven cycle of frontline treatment available to all eligible patients with MRD.
alpha three builds on the growing understanding that the administration of CAR T therapies to patients with low disease burden improves both safety and efficacy outcomes. Semi-subs Phase 1 safety profile with low rates of CRS and I. Ken's already permitted to use in the outpatient setting in relapse refractory patients. It may further improve in patients with no radiological evidence of disease was incredibly exciting is that the outcome of this pivotal trial could allow Fermacell to be embedded in the frontline setting where autologous therapies are far less feasible. Why consolidating response with an MRD positive result, post R-CHOP requires immediate and definitive actions prevent an impending relapse.
A onetime treatment with MSL could happen roughly two to three days post MRD positive test results. As we have seen, autologous CAR-Ts have had difficulty penetrating community cancer centers and accessing earlier line patients use of stem cell won't rely on the same complex logistics that have hindered CAR T adoption normal. There will be a reliance on referrals as the intent is for CAR T to be available in these communities Cancer Centers and allogeneic stem cell is what these doctors have been waiting for as entry to the modality in their centers.
We believe these differentiated attributes of semi-soft cannot be reproduced by autologous CAR T specifics or any other treatment modality. Start-up activities for Alpha three have been initiated. The study will randomize approximately 230 patients who are MRD-positive at the end of frontline therapy to either consolidation was MSL for the current standard of care, which is observation that design with a primary endpoint of event-free survival will initially include two lymphodepletion arms, one with standard fludarabine and cyclophosphamide, plus ALLO-647 and one without ALLO-647. The trial start as planned for May have catchment centers, including community cancer centers were most earlier line. Patients seek care. The outcome of this pivotal trial could allow myself to potentially improve, generates and become the only treatment approved for frontline consolidation, which the potential to significantly reduce the need for CAR T and in later lines. We look forward to answering any additional questions you have on our pipeline during the Q&A. I'll now hand the call over to Jeff.

Geoff Parker

Thank you, Zach. I like to echo David's comments made at the beginning of this call. It's been a very exciting few months. Speaking with current and prospective investors, the enthusiasm expressed for our strategy has been greatly appreciated and inspirational for our team. Such broad and unanimous enthusiasm is something that is unique in my career. We look forward to having ample opportunity to continue to share our vision and program updates throughout the year, especially on Alpha 3, TRAVERSE, our CLL trial, and ALLO 329, our CAR T 2.0 for autoimmune disease.
Our vision is bold, and we recognize the cash runway is critical. We are pleased that the changes we've made following our announcement in early January have focused the strategy and extended our runway into 2026, but acknowledge that extending the runway must remain a focus. Rest assured that while we actively managed costs, we will also be actively pursuing opportunities to build our cash reserves.
We do, however, have a strong cash balance ending 2023 with $448.7 million in cash, cash equivalents and investments. And we have no debt. As we look ahead to a full year 2024, we expect the cash burn of approximately $190 million. We expect our full year 2024 GAAP operating expenses to be approximately $280 million, which includes estimated non-cash stock-based compensation expense of approximately $60 million.
From a longer-term perspective, we continue to forecast that our cash runway will support our operations into 2026. This guidance excludes any impact from potential business development activities. Full year 2023. Research and development expenses were $242.9 million, which included $31.9 million in expenses associated with non-cash stock-based compensation.
For the full year 2023, general and administration expenses were $71.7 million, which included $34 million of non-cash stock based compensation expense. For the full year of 2023, our net loss was $327.3 million, or $2.09 per share, including non-cash stock-based compensation expense of $66 million and $13.2 million in non-cash impairment of long lived asset expense.
With that, we will now open the call for your questions.

Question and Answer Session

Operator

Thank you. As a reminder to ask a question, you will need to press star one on your telephone. To remove yourself from the question queue, please press star one. Again, you will be limited to one question before returning to the queue. Please stand by while we compile the Q&A roster. Our first question comes from the line of Tyler Van Buren up to the Cohen. Your question, please. Tyler.

Tyler Van Buren

Great, guys. Congrats on all the progress during the quarter. So I want to first ask about your autoimmune approach this time around. I personally build November to R&D Day where we saw response and renal cell without our six or seven zero to full FCA regimen.
So I'm glad to see that technology being deployed the allo three two nine for autoimmune disease. However, removing lymphodepletion, all together in AID. takes another big step further. So why do you think this is feasible in autoimmune? And how would you intend to test that in the early innings of clinical trials?
And maybe for a second question or have a question, forgive me. Could you just briefly talk about the potential impact from the bio secure bill, and we'll shoot to our jeans business?

David Chang

Hi Tyler. Dave Chang here. Hey, thanks for your questions. And I like how you sort of squeeze in that have questions after the first one on the outlook creatinine, I mean this is a product from the design to how we are in our manufacturing. It's really built on being able to differentiate our 329 from a from other there CAR T products that's going into building in indications.
And this is all ready getting pretty crowded place. I mean, the key differentiation has that had commented during the during the prepared remarks is really that baseball's one, this is a deal of seating. I can CD70 car and what that allows the our three tonight to do is not just completing the pathogenic B-cells. It can also deeply CD70 positive activated T-cells, which we believe play a pretty significant role in the order. You mean disease itself.
The other part is in the back to this concept of lymphodepletion, being able to deplete activated T-cells now allows us, we believe I look 329, oh, let's CD70 or containing products to work well, even as an allogenic CAR-T product without being dependent on having to use, I CD52 antibody. So one of the starting point for us is a lymphodepletion is very much on par with little color is CD19 CAR-T players are going, but we think that we can go even further west CD70 dagger can do is through going after activated T cells. And it will either the expansion is much greater. And also it has potential to start tapering off while eliminating the components of lymphodepletion, either fludarabine, all cyclophosphamide.
And it's not just the lavatory concept. We actually have clinical data coming from our CD70 or I look through and six program from the traveler study. So I think this is going to be a very interesting proposition that we believe is critical and not in that just to conduct this study rapidly and autoimmune indications, but also for the future commercial success. And that sort of at least to the third point of our 329, which is really the scale ability, not only as an allogenic. We also believe in the autoimmune indications in them, the duration of the persistence to I don't think we need a long duration of CAR-T persistence.
This is really a depleting the pathogenic lymphocytes deep enough so you can reset the immune system. So when we think about this for the indication that we're going in a week, I believe that the construct illustrate to nine can be effective at very low cell dose. So we are very excited.
And as we have said, this is one of the top priority programs that we have for 2020 full. And our intent is to accelerate the time line as much as we can currently, we expect to start in 2025 at the potential data readout, Phase 1 data readout, at least the early portions by the end of 2025.
So second question, I'm going to give a very brief response. I mean what's going on with a bias secure bill and wushi and allergan, and it doesn't impact Allergan at all. And in that also leads to something that we have been talking about for some time. We always have believed and that manufacturing is core to our business.
For that reason from early days, we built fully integrated CMC and manufacturing team that covers not just Process and Analytic assay development, but the supply chain and manufacturing. And that's really why we have invested in a building a fully dedicated allogeneic CAR T manufacturing facility, which we call CF1. And that will be a very differentiated and distinctive advantage as we strive to expand the use of CAR T not only in payments, but also in AID. where we believe the scalability is the key.

Operator

Thank you. Our next question comes from the line of Salveen Richter of Goldman Sachs. Your question, please, Salveen?

Salveen Richter

Good afternoon. Thanks for taking my question. With regard to your auto immune disease program and apart from dagger technology here, could you speak to that strategy here with regard to bringing in the Arbor, Christer base, gene-editing technology? And just how you think about and indicate patient preference and starting out. Just maybe help us understand about that profile you're looking for and then how you're going to go after specific diseases within the basket here?

Zachary Roberts

Thanks, Salveen. This is Zach. A great question. So what we what we wanted to do with the RBA new lease for us that would allow us to internalize that, that technology sort of independently and move away from the Talon technology. Um. And so the crisper based platform that Arbor brings will allow us to have some flexibility in introducing site-specific integration, which we also believe will improve this. The overall product profile and safety profile of this for this unique patient population. So really it is a a tool to allow us to go as fast as new directions with product design.
As far as the the clinical trial goes, as we get a little bit closer to the launch of that program will be eager to share more details. I'm willing to sort of say and speculate at this point that we we'll be looking carefully over the data that matures in the coming months on from the field and learning what we can learn about inroads being made into other indications. Of course, lupus is the indication in which the clearest clinical proof of concept exists. And so we'll be carefully paying attention to that. The design the study, again, we'll we'll get into that as we get a little bit closer.
But related to Tyler's question before, we are very much looking at how far we can push this lymphodepletion reduction as we can including potentially testing on no lymphodepletion at all. So stay tuned for more details on the clinical development plan as we get a little bit closer to the launch of the program in early 2025.

Operator

Brian Cheng, JPMorgan.

Brian Cheng

Hey, guys. Thanks for taking my questions today. Outlook. I'm curious if you can walk through your latest thinking around the Phase one for Allo 329 specifically, how many dose that you plan to execute? Are you doing dose escalation in autoimmune patients? And if so, which indications from expectations are Quiet Steel players now already in indications like lupus and myasthenia gravis? Thank you.

David Chang

Brian. Dave chang here. I'll take that question. Great question. What I can say is stay tuned, um, in terms of being a step up the dose escalation of lymphodepletion, I believe those are details that given our team's track history and conducting the clinical studies that can execute those pretty well, more like enough to think about the objective to start the Phase one study with 329. I mean, the three things that we have put about the differentiation coming from being able to go after B-cells and T-cells, that's more of a biologic clinical question that needs to be addressed through the conduct of studies and going after different indication. But also as we have called it, whether we can administer our three, two nine would reduce or more with no lymphodepletion and has the same type of immune resetting phenomena. I think that will be really the focus of how we designed the Phase one study. And of course, the I'm trying to get that. And so as quickly as possible. I mean that lead to that leads to a couple of different study designs. But all these things are being discussed right now.

Operator

Thank you. Please stand by. Our next question comes from the line of Michael Ng of Jefferies. Your question, please. Michael.

Hi. This is Matt on for Michael. I was wondering, you know, footing with an autoimmune focus and thinking about the first line study for Alpha three, how do you ensure that you'll be able to enroll the study? And I guess what gives you confidence in your ability to enroll the study in a timely fashion as a corollary, when would we be able to expect from some initial data from from these patients?

Zachary Roberts

Thank you. Hey, Matt, this is Zach. Thanks for the question. So as far as the first part of your question, why are we confident that this study will be able to and be enrolled quickly on it in a word enthusiasm. I think the what we have seen so far as we have reached out to investigators across the treatment spectrum from academic KOLs who have been part of the CAR T story for 10, 15 years, all the way to community oncology practices that that have a large volume of patients, but have not yet made the jump into CAR T.
The response to the study has been uniform and it's been extremely positive. And and we are seeing levels of engagement from investigators, clearing obstacles to open the program as quickly as they can. We've seen that left and right. So there is a there is a palpable level of enthusiasm around this concept, really driven by the possibility of curing patients after frontline and preventing a relapse from ever occurring. This is a very novel and innovative approach to artist studies and LBCL. when and people are really excited to be part of that.
And as far as data goes on, we as we get a little bit closer to the start of the study in midyear of this year, I think we'll be in a position to provide a little more clarity on on when enrollment is going to complete and when data will be available on. What we have said and I'll reiterate here is that we the study is designed to have a an interim analysis that is currently slated for middle of next year when we will examine MRD. conversion from positive to negative. Everybody that comes into the study will be MRD-positive. So we're looking for evidence of clearance of MRD as well as safety and translational outcomes.
And we will use that interim analysis to select the lymphodepletion arm that will be carried forward for the rest of the accrual period. So as we pass through that gate, we will make a modification to the study design, and that will be plainly visible to to all who are paying attention. And we will not, however, be able to share. There are some granular detail from that analysis because this study is pivotal from the very first patient enrolled. And so all of these patients starting again, middle of this year will count towards the overall and that's required for the pivotal study. So less shares results. We will not be sharing a data update at the middle of next year.

David Chang

And Brian, I would add I like the question about your focus on enrolling the pace of execution of the study, which I think is the key. When you know, when you look at what we're doing alpha three, I mean, that's built on all the data that we have generated from the ALPHA two in relapse refractory large pizza cell lymphoma setting. I mean, we shared that data before we had all of you. And this is really on par with autologous CAR T therapy, which I don't think any of the other antigens and a CAR T companies can say that yet.
And from the technical perspective, we believe that this highly derisked, I mean, after all, this is comparing against observation in a watch-and-wait. So we feel pretty good about that. Execution is the key. And frankly, I think in a study start and enrollment, I think that is pretty significant de-risking inflammation about the RP study. So stay tuned. I mean, our teams working really hard to make sure that we execute this study as quickly as possible.

Operator

Jack Allen of Baird.

Jack Allen

Thanks for taking the question and congratulations on the progress on kind of same vein as a last question. I wanted to ask about that interim analysis for middle of 2025. I understand that it sounds like you may not be playing out with the share the results. But any context you could provide around the number of patients are looking to have that data set? And is there and internal Barber you're thinking about that you're looking to reach as it relates to personnel in the study for past that interim analysis? Thanks so much.

Zachary Roberts

Hey, Jack, thanks for the question. And so we haven't gone into detail about how many patients are going to be included in that analysis on it. I'll say that it's sort of, um, you know that media and hopefully not too many, not too few. We want to have enough statistical power to make a good a good call. And with respect to the second part of your question, you know, how are we going? Is there an internal bar that we're going to be looking for? So there's really two parts to this, right? We want to make sure that we are improving upon on the standard of care, which is watch and wait.
And we think, as David pointed out, that we've largely derisked that question to our experience in phase 1. We know that MSL is an active therapy. So we think that we will be able to close that ball. But of course, we'll be paying attention to it. And then, of course, we have an additional set of criteria that will be using to make the selection of FCA versus FC. So this is a very well thought out prospectively designed analysis that we think is going to lead us to the right answer.

Operator

John Newman of Canaccord Genuity.

John Newman

Hi, guys. Thanks for taking the question, and thanks for the update. Curious if you could comment a little bit more regarding the potential targets in autoimmune disease. So obviously, your approach to targeting some other companies out there are also looking at CD. 19, but some are looking at CD. 20. Can we have additional companies with BCMA CAR-T that are sort of considering treatment of autoimmune disease, namely lupus? Can you say which targets could be better? And why obviously, different targets sort of crept up at different times during the life cycle of T cells, but just curious as to your Thank you.

David Chang

Yes. So income on a great question. And I frankly, I think this is a topic that we are sort of looking into. But ultimately, I believe that when you look at the oncology, any of these cells, the targets that you have mentioned, CD19, CD20 and BCMA, if you look at the at the coverage of CD19 expression, that's probably a more broad and probably a better suited than their targets. But this is something that we also have to find out from from a clinical data as different players, testes different targets. The other question around the indications that we are interested in, we can sort of think about this from generating early proof of concept of not requiring a lymphodepletion if that is the primary objective. And actually, there is indications where the proof of concept has been established with a CD19 CAR T would be very good.
And also lupus nephritis is in a commercially very attractive indication. This was a lot of us is definitely into play. No, it's getting crowded. But remember, our three to nine has a very distinct and differentiated approach. So if we can differentiate from others, I think we have a good we will have a good traction even in the crowded field, but also being able to go after us, the activated T-cells off the page essentially opens the door to other autoimmune diseases where going out to see nice and alone may not be sufficient and multiple sclerosis as a class of diseases, one autoimmune diseases that affect the nervous system, I think that's also falls.
And so frankly, yes, we have to be focus and we have to go after certain indications. But you know, right now, I don't think we have to decide and we have enough time to finalize this decision in next three to four months. So stay tuned.

Operator

Thank you. Our next question comes from the line of Sami Corbin of William Blair. Question, please.

Hi, this is the kl on for sami Karl and thanks for taking the question. So given the number of CAR T cell companies pursuing autoimmune disease indications, I think about competing for patients and field trials would have been more focused on enrolling patients in the US or ex-US or a combination of both?

David Chang

I think that's a relatively that is simple to me. I mean, when you think about in a down month, positive fund companies are taking different asset sensitivity and indication. Yes, it is true. But when you think about in a number of potential patients that are out there, I was in the current clinical studies are covering, is that not even a tip of an expert?
I mean, you're probably talking about in a field that 100 patients out of a 20,000, 30,000, 100,000 potential patient population that we can go after. So our view is we are less concerned about that as long as we maintain that differentiation. And frankly, if you can get rid of the lymphodepletion, I think the opportunity to do a quick credit development program that just becomes a more real and something that we can easily do very quickly.

Operator

Thank you. Our next question comes from the line of Kelcy Goodwin of Guggenheim. Please go ahead. Chelsea.

Kelsey Goodwin

Thanks for. and good afternoon and thank you. And how do you think about the ideal placement for current key given kind of the agents, patient population and the durability that we see with BTK and BCL-2 inhibitors? Thank you.

Zachary Roberts

The question was around the durability that we can expect?

Kelsey Goodwin

What are the positioning and what kind of patients would would you want to get on this given kind of the age at diagnosis and how how durable the responses are with the inhibitors that are already approved?

Zachary Roberts

Yes. Okay. Thank you. So well, as a reminder, the the on that stuff, he will enroll patients that have inhibitors and BCL2. Now there is a non-covalent BCLSBTK. inhibitor, part of group net debt's been approved and that has shown that in a similar patient population. There is some benefit to that to that drug. However, some similar to the established modalities, this is not curative. And so what we what we have seen from the autologous experience in CD. 20st CLL is that some patients, a significant fraction of these patients can actually had very meaningful, durable, complete remissions that go on for months or even years. And so in a patient population that has failed these prior therapy. So number one, I think that the modality is is promising in this patient population.
Number two, I'll point out that, you know, just looking at our experience from from LBCL. is that our toxicity profile is is wholly consist and with a somewhat more frail population with very low rates of high-grade CRS. And I can and could inconsistent with outpatient dosing, which we do have experience with. So while we are getting our feet wet with this Phase 1 study and getting ready to share data later on this year, we will be paying very close attention to how that toxicity profile plays out in this patient population as well as being able to meet or even exceed the bar. So that has been established by the by the autologous players.

Operator

Thank you. Our next question comes from the line of Reni Benjamin of JMP Securities. Please go ahead. Randy.

Reni Benjamin

Thanks, guys. Thanks for taking the questions and congrats on the progress of. Maybe just continuing with the thought of questions around CLL, what would you consider to be kind of a go no-go results that you would like to see by the end of this year? I know there's only going to be about 12 patients worth of data. Just how do you how do you plan on kind of dissecting that?
And I guess just as a second part of that, just given your experience with LBCL, do you think there might be an opportunity to move CSL to some type of a consolidation or more of a front-line treatment in combination with drugs that are already out there? I remember way back when, okay, you know, we're thinking about combination studies in a front-line setting and just wanted to know how you guys are thinking about. Thanks.

Zachary Roberts

Yes. So as far as the bar for internal decision making, of course, we'll watch the data as it rolls. And but I'll again point out that the bar is not all that high here. And actually, that's one of the things that why we believe that moving into CLL is exactly the right thing that we should be doing with Temasek because the data that's before the FDA right now suggests that, you know, an improvement of 50% [ORR] and a sub-20% [CR] rate is something that is, you know, probably well, not probably as attractive to the treating physicians and patients who are in this predicament of having failed the approved therapies. And so we'll be watching the the FDA's response, Hans, to that data set very carefully. And as our data matures, being able to make a decision about whether the whether to move that into a Phase 2 registrational study.
As far as the other question goes with respect to consolidation and or combinations, I do think that that is an attractive avenue to pursue. And in fact, our our our focus in consolidation and large B cell with Alpha three is a testament to our belief that a consolidation strategy or treatment with a with CAR T cells when the diseases that are relative nadir is a very interesting proposition and can be applied to other indications as well. Combinations a little bit more of a challenging idea, but it certainly has been fleshed out to do that. And so we'll be looking at that carefully as the program matures as well.

Operator

Thank you. Our next question comes from the line of Kalpit Patel of B. Riley Securities. Please go ahead. Kathy.

Kalpit Patel Patel

Yes, hey, guys. Thanks for taking the question. Maybe just one on allo three to nine. Can you discuss any thoughts on broader immunomodulatory margin maturity effects beyond direct center toxicities that has any impact on regulatory T cells? Is you have targeting CD70? And how might these effects influence outcomes for autoimmune disease patients?

Zachary Roberts

Thanks, Kalpit. Good question. So that is the detailed work on sort of the the subsets of T cells is ongoing in the context of our three one six program. And so really trying to understand, are there certain compartments within that T cell lymphocyte population that are more differentially affected by by CD. 70 targeting therapy. And so we're doing that work in the context of our ongoing three, one six.
And in fact, a good strong support for this idea of being able to target activated T cells has now been demonstrated, as David mentioned, from the translational results from the TRAVERSE trial. So I think what we can take away knowing what we know from our in vitro work and the clinical trial with CD. 70 car is that we do see differential suppression of activated T cells. And we know that those activated T cells and B, they conventional or regulatory are are involved in autoimmune pathogenesis. And so I mean, there's literature that supports the role of CD. 70 and certain autoimmune disorders like lupus.
And so we think that in addition to the dagger effect, which is one of the key reason is that we're pursuing CD70 has a dual CAR with our 329. We do think we'll be able to modulate the activated the specific activated subset of those T cells. And so we'll look at the careful Tino subpopulations as we as we execute the three one six study. And of course, we'll be paying close attention to that within 329.

Operator

Thank you. Our next question comes from the line of Luca Issi from RBC Capital. Please go ahead. Luca.

Luca Issi

Great. Thanks so much for your question and congrats on the private cities asks, can you just expand a little bit more on the interim look in the mid 2025? I think when you are running the trial in the third line setting, the FDA is going to ask you to ship PFS superiority, winning actually the [anti-52 versus nuances no anti-52] to it dedicated randomized trial.
However, it looks like the FDA is not okay. And just showing patients converting from energy policy to MRD-negative within the context of the C pivotal trial and actually not a separate trial, which is not randomized, unlike feels to me that the FDA has kind of lowered the bar here despite here action movie in earlier studies. one. Would that be fair to, if so, what drove that change in posture from the regulators because they're much appreciated.

Zachary Roberts

So I don't I don't say Thanks, Luca, for the question. I don't think that there has been a change in the FDA's opinion on what would constitute a contribution of effect data package. I think of what we have done in the design of alpha three is condense that what was two trials in the third-line setting into a single trial in the frontline consolidation setting. So we've really got to, in a way of speaking a trial within a trial. And the first part of the study that will culminate with the interim analysis next year is is designed to generate the contribution of effect that will be that will support the registration of our six four seven.
Now that said, you know, the reason that were randomized and is because we want to actually address the scientific question of whether our oh six four seven is truly retractable roof wired in these patients with no radiographic evidence of disease. And so there is still a chance, I would say a good chance that we select beyond that does not even that does not contain our 647. So but be that as of May. The reason that we have designed it, how we have done it is you specifically address the FDA's requirement for COE for 647. So I would not say that there's been a change in regulatory stance there.

Operator

Thank you. Our next question comes from the line of Asthika Goonewardene from Truist. Please go ahead. Ask Erica.

Hi. This is chronograph core consulting and the question following up on CLL. License-only generated on a 18% CR rate on how my for efficacy of online to make CAR T. compared to autologous and CLL, and particularly considering that potentially superior T4 fitness and of what data, which I'd like to see in evaluating the efficacy of AlloCAR T in this context?

Zachary Roberts

Thanks Carina. So I think I like the way you asked that question because I think it really speaks to our primary motivator for us opening this trial. And that is that we believe that the underlying T cell fitness coming from a healthy donor derived product is going to be superior to the T cell fitness that is derived from a patient leukapheresis because CLOs are notoriously immunosuppressive malignancy, number one, number two, often those T cells are surrounded by a very high circulating leukemic burden, which makes isolation of thos e cells for manufacturing all the more difficult.
We we Dodge both of those those problems starting with healthy donor material. So we think that there is a chance that we will actually have a a meaningful improvement over what has been shown by autologous. But of course, that's why we're running the experiment and sort of address what we think of the target is here, of course, to 18% CR rate that's been established as potentially registrable. We'll see what happens with the the the decision by the FDA there. But we think that given the comparability that we believe we've shown and large B-Cell against autologous products that we should at least be able to meet meet that.

Operator

Thank you. Our next question comes from the line of Laura Prendergast of Raymond James. Your question, please, Laura.

Laura Prendergast

Thanks for taking the question. I'm just curious, as MRD testing here, as expected becomes more broadly used, are you at that having any issues and rolling alpha three X assistance? Okay, some patients will be randomized control arm with no therapy. How do you think about this? And do you expect now in the future competition in this setting given the progress of MRD testing?

Zachary Roberts

Thanks, Laura. So so we don't we are not worried in the least about on the patients who are going to be randomized to observation. That is the current standard of care. And that means that these patients there is no data anywhere let alone an approved agent to direct the physician. It has to offer another line of therapy to patients who are in the observation arm. So we don't think that there are in fact, we know for for for a fact, based on the work that we've done already in during the study startup that there that there is wide agreement that this is the most appropriate management for these patients, which is the current standard of care observation.
These patients will be monitored very closely in the context of a clinical trial probably as closely if not more so than they would be if it were, they not participating in clinical trial, that's the nature of clinical investigation. And this is going to be part of why we think patients will be willing to sign up for this study.
And as far as competition goes from, there is a good chance that at some point we will see some company in the developer options with MRD only disease. We do think that we have a unique product profile with some onetime administration. So there's no need to for a long period of treatment to our maintenance therapy. This is, as we said, kind of a settlement cycle of treatment. These patients can get and just go home and move on. And number two on, there's these patients can progress very quickly after they complete front-line therapy and they have MRD disease.
So being able to act definitively and very rapidly and our mind you that we initiated treatment within two to three days after patients are enrolled in our third line study. So we know that we can add we can affect this treatment extremely quickly. So we think we have a built-in advantage with our modality, and that's on top of the rest of the strong lead advantage that we have having launched this study for any of our competitors.

Operator

Thank you. Our next question comes from the line of William Pickering, Bernstein. Please go ahead. William.

William Pickering

Hi. Thank you for taking my question. In your alpha three trial you've talked about including community centers. Could you speak to the level of interest that you're getting from these centers? Do you expect it to be a large or small percent of total sites in these centers need to RDP fact accredited to participate? Thank You.

Zachary Roberts

So I will say that the reception that we have gotten from these community practices has been very, very positive. And very, there's a high level of engagement and enthusiasm. Many of them are moving extremely quickly to be ready to open this study on. There's even a little bit of friendly competition among some of them to really be the first to open. So we've been very encouraged by the by the reception that we have gotten on.
As far as the percentage goes, it's going to be that we're going to we're definitely owners because they are as excited about this concept as a community oncologist. So there's going to be a continuum. We don't exactly know yet. We haven't completed the full selection of the entire panel of of programs, but I will say that there will be a substantial on a percentage of patients coming from these community practices in the overall study.

William Pickering

Thank you.

Operator

Thank you. I would now like to turn the conference back to David Chang for closing remarks. Sir. Okay.

David Chang

Thanks for joining on our call today and your continued support. We are more excited than ever about the potential for allocating and opportunity to fulfill the promise of allogenic CAR-T for patients with cancer and now extending that promise to patients with autoimmune disease. With our CAR T 2.0, our three tonight as someone who has been involved in developing cell therapies, I'm particularly excited about what's happening in the field today. Thinking differently, that is exactly what is needed to appeal this new resurgence in cell therapy. I look forward to providing updates to our exciting programs throughout the year. With that, goodbye.

Operator

This concludes today's conference call. Thank you for participating. You may now disconnect.