Allogene Therapeutics - Q3 2023

Transcript

Operator (participant)

Hello, and thank you for standing by. Welcome to the Allogene Therapeutics third quarter 2023 conference call. After the speaker's presentation, there will be a question-and-answer session. To ask a question during this session, you will need to press star one one on your telephone. You will then hear an automated message advising you that your hand is raised. To withdraw your question, please press star one one again. Please be aware that today's conference is being recorded. I would now like to turn the call over to Christine Cassiano, Chief Corporate Affairs and Brand Strategy Officer. Ms. Cassiano, please go ahead.

Christine Cassiano (EVP of Corporate Affairs and Brand Strategy)

Thank you, operator, and welcome to our call. Today, after market close, Allogene issued a press release that provides a business update and financial results for the third quarter of 2023. This press release and today's webcast are both 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 Office; Dr. Zachary Roberts, Executive Vice President of Research and Development and Chief Medical Officer; and Geoffrey 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, and 2023 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 earnings press release and the latest SEC disclosure documents. You are cautioned not to place undue reliance on these forward-looking statements, and Allogene disclaims any obligation to update these statements. I'll now turn the call over to David.

David Chang (President and CEO)

Thank you, Christine, and welcome to all listening to our call today. The last few weeks have been exciting in the field of cell therapy, from an uptake in the power of CAR T cells and the release of abstract this morning for the upcoming American Society of Hematology meeting, to witnessing the potential of CAR T therapy beyond oncology. It is clear that we are just at the beginning of what's possible for patients with this modality. While indications outside of oncology have been the focus of the field as of late, something we are keeping a keen eye on, I will focus our call today on CAR T in oncology. Throughout the decades, cancer therapies have come in great waves.

Cytotoxic chemotherapy was the first wave, spending most of the twentieth century as fundamental discoveries in blood cancers gave way to increasingly sophisticated combination therapies that could be used against solid tumors. The second wave was monoclonal antibodies, a scientific breakthrough that even today continues to fuel innovation with follow-on technology platforms. I would argue that this wave also includes antibody-drug conjugates, bispecific antibodies, and bispecific T-cell engagers. The third wave has been a more gradual emergence of targeted therapies in today's omics era. Pathways that govern the behavior of our cells have been delineated, paving a way to precisely enter the disease. We are now at the beginning of a fourth great wave, the era of engineered cell therapy.

The enablement of synthetic biology to harness the power of immune cells is now feasible through the convergence of knowledge of cellular pathways and technological breakthroughs in gene editing and cell engineering. But this fourth great wave can only be fully unlocked when industry makes CAR T accessible to all eligible patients. This was an important topic during recent discussions at both the Future Summit hosted by SET, as well as at the American Society for Transplantation and Cellular Therapy-sponsored Accelerate Forum on a panel moderated by Dr. Peter Marks, Director of the Center for Biologics Evaluation and Research, and Dr. Marcelo Pasquini of the Center for International Blood and Marrow Transplant Research. At Allogene, we believe that the key to unlocking this potential is allogeneic CAR T, and if you will, creating the Konami code for cell therapy.

For those who know video games, the Konami code was originally a simple sequence of buttons that would give a full set of power-ups to make testing easier for developers. The modern-day concept of this code is no longer just about making a game easier. Rather, it is now unlocking hidden expert modes, enabling expansion of the game. That is exactly how we are thinking about our platform. It is creating the Konami code for allogeneic cell therapy, a code that can be applied not just in the industry's first potential equivalent trial of an allogeneic CAR T product, but in other harder modes, such as early aligned trials, solid tumors, non-oncology indications, and next-generation products. We look forward to the months ahead, where certain scientific aspects of this code will come to light, unlocking new opportunities and broadening patient access to the fourth great wave.

Before I turn the call over to Zach to give a brief overview of what will be presented at the Society for Immunotherapy of Cancer and what's expected at ASH. I would also like to take the opportunity to officially welcome the newest member of our leadership team to his first Allogene quarterly call, Geoff Parker.

In this especially challenging market, Geoff's extensive experience in biotechnology across all aspects of finance and business development strategy will be of tremendous value to Allogene as we advance our critical pipeline assets and explore new opportunities. I am confident he will be instrumental to our success as we navigate the next chapter. I would now like to turn the call over to Zach.

Zachary Roberts J. (EVP of Research and Development and CMO)

Thank you, David. While we focus on execution of our potentially pivotal ALPHA2 global trial with ALLO-501A in relapsed/refractory large B-cell lymphoma, our 2023 data readouts have been designed to answer foundational questions that support the viability of an allogeneic CAR T product. Over the summer, at the American Society of Clinical Oncology annual meeting, the European Hematology Association Congress, and the International Conference on Malignant Lymphoma in Lugano, we shared the long-term durability data from our phase I trials that answered one of the most important questions in the field: Can an off-the-shelf CD19 CAR T product candidate demonstrate durability comparable to an autologous CAR T therapy in large B-cell lymphoma? In CAR T, the best surrogate for duration of response is a six-month CR rate.

Based on the data from patients who received our phase II regimen during the phase 1 trial, we have now shown that our 6-month CR rate is comparable to what has been reported in the pivotal studies of Kymriah, Yescarta, and Breyanzi. In all of these presentations, our safety analysis included all 33 CAR T-naïve LBCL patients who received Allo product. Treatment was generally well-tolerated, with no cases of Grade 3 or higher CRS and no cases of ICANS or GVHD. Cytopenias and infections were manageable and comparable to the experience with autologous CAR T therapies in patients with relapsed/refractory LBCL. We showed patients' neutrophil and lymphocyte counts beginning to recover within the first month of infusion and achieving baseline levels with kinetics similar to autologous cell therapies.

Comparability of immune reconstitution in patients receiving investigational ALLO-501A to those who receive autologous products yields important insight into our comparable infection rate. But we wanted to dig deeper and address outstanding questions posed as it relates to the safety profile of ALLO-647, our investigational anti-CD52 monoclonal antibody, when used in conjunction with standard low-dose flu/cy. That will be the focus at this year's annual meeting of the American Society of Hematology. At ASH, we will have a comprehensive safety review of all 85 patients treated in the phase I ALPHA and ALPHA2 studies in LBCL and follicular lymphoma to characterize the overall safety profile when ALLO-647 is added to standard lymphodepletion. Because of the risk of allogeneic rejection by a patient's immune system, creating the necessary window of persistence for an allogeneic CAR T likely requires an enhanced approach to lymphodepletion.

Different approaches have been used in other allogeneic clinical trials, including high-dose chemotherapy, that might be associated with severe toxicity. The results of our trials reinforce our belief that in the LBCL patient population, our unique and proprietary lymphodepletion regimen can set the right conditions for our cell products to induce deep and durable remissions while keeping the safety in line with approved autologous CAR T therapies. Our nuanced understanding of lymphodepletion based on the breadth of our trials has fueled our early-stage research. This weekend, we look forward to poster presentations at the Society for Immunotherapy of Cancer annual meeting, highlighting our next-generation cloak and dagger technologies designed to help enhance engraftment, expansion, and the persistence of Allo CAR T cells.

In LBCL, while we continue to be pleased with the overall profile demonstrated in our trials, we fully recognize evolving practice patterns with autologous CAR T therapies moving into second line. Our CD19 program strategy contemplated this challenge, and we are tackling this on two fronts. The first strategy is in the phase II clinical trial execution, and we've focused on increasing the global footprint of our trials. ALPHA2 is now open to enrollment in the U.S., Canada, Europe, and Australia. Our phase II EXPAND trial, designed to demonstrate the superiority of an ALLO-647-containing lymphodepletion regimen over a regimen of Flu/Cy alone, is open to enrollment in the United States and Europe. The second strategy lies in the design of an earlier line trial and how we ultimately think this market will evolve. We are all very excited about our intended approach.

When all aspects are locked, we look forward to sharing with you more about this trial and believe it will address many questions you have about our overall approach to treating LBCL. Lastly, I'd be remiss if I didn't talk a bit about our phase I TRAVERSE trial with ALLO-316. We do not take lightly the responsibility we carry to demonstrate the potential of an Allo CAR T in solid tumors. As such, we have taken a very deliberate approach and are proud of the way in which we are conducting this trial. We've continued to gain incredible insights for CAR T in solid tumors that we hope will advance this trial into a potentially pivotal phase, and even more importantly, provide another option for patients with advanced or metastatic renal cell carcinoma.

The importance of such data to our investors and the medical community at large cannot be understated, so we will now target our next update for an academic forum in early 2024. I will now turn the call over to Jeff.

Geoffrey Parker (CFO)

Thank you, Zach, and good afternoon, everyone. In my first few weeks as part of Allogene, I've had the chance to speak now with a handful of our covering analysts, and I look forward to getting to know all of our analysts and investors over the next few months and years to come.

In these early conversations, the number one question I get is, why did I join Allogene? For me, there is a simple answer. I've been in this industry for over 30 years, and I firmly believe that this is one of the best management teams I've ever encountered. As a quick note regarding my background, I worked at Goldman Sachs from 1986 to 2009 in investment banking, ultimately running the West Coast healthcare banking practice for the last 10 years of my tenure at the firm. Following my time at Goldman Sachs, in 2009, I decided to move to the company side to serve as a CFO, as well as to serve as a board member with a number of healthcare companies, which I have now done for the last 14 years.

Geoffrey Parker (CFO)

Fast forward to this past summer when I received a call from David. I was immediately intrigued by the opportunity to be a part of this team and to play a role in fulfilling the promise of how allogeneic CAR T products could address the access gap to this important modality. Let me now turn to another of Allogene's strengths, our balance sheet and the careful way in which we manage our resources. We ended the third quarter with $497.7 million in cash, cash equivalents, and investments. As noted on our last quarterly call, based on current assumptions, we expect our cash runway to fund operations into the second half of 2025. In the third quarter of 2023, our research and development expenses were $46 million, which includes $6.7 million of non-cash stock-based compensation expense.

General and administrative expenses were $17 million for the third quarter of 2023, which includes $8.6 million of non-cash stock-based compensation expense. Our net loss for the third quarter of 2023 was $61.3 million, or 37 cents per share, including non-cash stock-based compensation expense of $15.4 million. We continue to expect a decrease in cash, cash equivalents, and investments of approximately $230 million for the full year of 2023, and full year 2023 GAAP operating expenses to be approximately $340 million, which includes estimated non-cash stock-based compensation expense of approximately $80 million. This guidance excludes any impact from potential business development activities. With that, we will now open the call for your questions.

Operator (participant)

Thank you. As a reminder, to ask a question at this time, please press star one, one on your telephone and wait for your name to be announced. To withdraw your question, please press star one, one again. We ask that you please limit yourself to one question. One moment while we compile our Q&A roster. Our first question is going to come from the line of Michael Yee with Jefferies. Your line is open. Please go ahead.

Michael Yee (Managing Director and Senior Biotechnology Analyst)

Great. Thanks. Good afternoon, guys. Thanks for the question. I just wanted to ask on the ongoing progress of the potential pivotal trial, you said you had expanded into different countries. Can you just give us a sense of, appreciate it's still early, sort of the blocking and the tackling, the, you know, expectation for geographic mix and, you know, the progress you're making in terms of the types of patients you think you are getting, and whether there's any challenges with other competitors or other types of CAR T, which are things that are weighing on people's minds? And then as a follow-up, you did mention that CD70 is important, and I heard that. Can you just clarify why the data would be 2024, not 2023? Maybe you could just shed some light on that. Thank you.

Operator (participant)

Please remain on the line. Your conference will begin shortly. Again, ladies and gentlemen, please stay on the line. We will begin shortly.

Geoffrey Parker (CFO)

Operator, are you still there?

Operator (participant)

I am, Mr. Yee. Just give them a moment. They're having technical issues, and they will be back with us.

Geoffrey Parker (CFO)

Okay. Thank you.

Operator (participant)

You're welcome. Hey, Mr. Yee, could you do me a favor, sir, and go ahead and state your question again? They are reconnected now.

Zachary Roberts J. (EVP of Research and Development and CMO)

I remember the question just, just fine, Michael. Thank you so much, and apologies for the technical glitch there. So I don't know how much you heard, Michael, so I'll just start over from the beginning. So regarding the first question around ALPHA2 enrollment or the potentially pivotal programs with CD19, we're really excited about the progress we've made on the regulatory front. And now we have approval in multiple geographies for both programs, and we are enrolling ALPHA2 in U.S., Canada, Europe, and Australia, and EXPAND in U.S. and in Europe.

As far as the patient mix that we anticipate having, we're still bringing in patients from the U.S., and so we don't exactly know how this is all gonna shake out in the end, but it will be a nice mix with a significant fraction coming from U.S. And then, I think probably a large number coming from ex-U.S. as well. And the types of patients that we are getting is very much consistent with the patients that, you know, we have set out to enroll based on the eligibility criteria. And, again, we're really focused on enrolling patients who would have been very similar to those that were enrolled in the autologous pivotal studies from a few years back.

For the second question on 316, so as far as, you know, the timing of the data update, we were sort of always planning towards the end of this year, beginning of next year. As we mentioned in the prepared remarks, that, you know, we are just really keen to make sure that we are executing the study well and then also updating with the data, and taking that all very, very seriously and not rushing things. So, we don't expect that the delay will be substantial in that data, and we just wanna make sure that it meets everybody's expectations. Hopefully, you heard that.

Geoffrey Parker (CFO)

That's good. Yep, all good. Thank you.

Sami Corwin (Biotech Equity Research Analyst)

Operator, do we have the next question?

Operator (participant)

Our next question is gonna come from the line of Sylvie Richter with Goldman Sachs. Your line is open. Please go ahead.

Anu Midan (Analyst)

Hey, this is Anu Midan for Sylvie, and thank you for taking our question. Could you first provide an update on the progress of enrollment in the TRAVERSE study? Have there been any headwinds there? And then just a second one on the Cloaking and Dagger technology. I guess, what other programs are you thinking to incorporate the technology in, and would multiple myeloma be a possible direction there, given the profile to date? Thank you.

Zachary Roberts J. (EVP of Research and Development and CMO)

Thanks very much. Again, this is Zach. So as far as the TRAVERSE enrollment goes, I will say that the enthusiasm that we've been communicating all year since the announcement of the data at AACR earlier in 2023 has very much persisted, and in fact, we are continuing to get incoming interest from sites that aren't participating in the trial actively. So I would say that as far as the level of interest goes, it's really quite impressive. And that's really coming down to that efficacy that we showed back in AACR, reminding everybody that the options for these patients are very slim, and the profile that we showed in April was pretty encouraging, to say the least.

On the second question around Cloak & Dagger, so the specifics around how, you know, which CAR target we choose to pair with that technology? You're absolutely right. We can do it with either CD19 or BCMA, and you're right that the BCMA field is evolving, continuing to evolve, and just a preliminary look at the data from ASH certainly does look encouraging for patients' perspective. And internally, we have data to show that we can pair our Dagger technology with either CD19 or BCMA. So we look forward to sort of sharing more specifics as far as next clinical candidate goes, in the coming months.

But, the data that we do show at 50 is paired with the CD19, so that is a very nice proof of concept for what we can do with the Dagger.

Operator (participant)

Thank you. And one moment for our next question. Our next question is gonna come from the line of Tyler Van Buren with TD Cowen. Your line is open. Please go ahead.

Tyler Van Buren (Managing Director and Senior Biotech Equity Research Analyst)

Hey, guys. Thanks very much for the update. Can you talk about the ongoing enrollment of the EXPAND trial and, in particular, with the ALLO-501A-only arm? And if you think it will complete enrollment, given the lack of ALLO-647 being used. I guess my question is, if enrollment ends up being increasingly challenged, which I believe it should, would you aim to go to the FDA by the end of next year with data that you have available at around the same time as the ALPHA2 readout? And could that be sufficient?

Zachary Roberts J. (EVP of Research and Development and CMO)

Thanks, Tyler. Again, this is Zach. So, as far as the enrollment to the two arms goes, there's no choice, obviously, that investigators or patients can make there. That's a randomized trial, and so that's how that will unfold. And, and so we don't expect necessarily there to be a disparity in the enrollment. If the patients pull out of the study because they get randomized to one arm or the other, that patient will be replaced. The second part of your question around, you know, what data and when would we go to the FDA? It's, your question is very much centered on how we're thinking about it.

So as the data from ALPHA2 begins to mature, and we have something, you know, tangible to take to the FDA, I do think that we would go at the same time with what we have from EXPAND. And, as a reminder, this study is supported with the Data Safety Monitoring Board, who will also be able to weigh in on the emerging data from that, but that is absolutely a part of our strategy.

Operator (participant)

Thank you. One moment for our next question. Our next question is gonna come from the line of Brian Chang with JP Morgan. Your line is open. Please go ahead.

Brian Chang (VP and Equity Research Analyst)

Hey, guys. Thanks for taking my question. On CD70, what will be needed for you to take the program into the pivotal stage? Can you give us a preview on what will be deemed as the bar to gauge success early next year before dedicating resources to push this program to the next stage? Thank you.

Zachary Roberts J. (EVP of Research and Development and CMO)

Thanks, Brian. So what we're looking for, I think, in this program is in the neighborhood of what we have shown already, as it pertains to the CD70-positive patients. As you'll recall, in the AACR presentation, we had two groups of patients. One group whose CD70 expression was low or unknown, and then one that was measurable, and that was a range of expression levels within that group. And in that CD70-positive group, we saw a response rate of about 30%. So we think that that is would be a meaningful improvement for what patients currently have on offer, and that includes some of the data that's been released more recently. So if we can come in around that mark, we do think that is a path towards a pivotal program.

Operator (participant)

Thank you. One moment as we move on to our next question. Our next question is gonna come from the line of Jack Allen with Baird. Your line is open. Please go ahead.

Jack Allen (Senior Research Analyst of Biotechnology)

Great. Thanks so much for taking the questions. Maybe first on EXPAND, I was wondering if you could comment on the geographic build-out there. Are you fully satisfied with the footprint in the US and EU, or do you expect to expand into additional territories there? And then just briefly on the earlier line strategy, you made some comments around, finalizing that and then hopefully providing some updates. Do you have any, additional comments around timing as it relates to locking in that strategy?

Zachary Roberts J. (EVP of Research and Development and CMO)

Thanks, Jack. So as far as EXPAND goes, we are still making progress there. We will intend to bring on Australia in the coming weeks there, so we are still working to expand the footprint there. And even within the countries in Europe, we're still adding sites. So we're still in execution mode for both ALPHA2 and EXPAND and bringing on new sites to grow that footprint to support enrollment.

And then, for the early line study, so, I will say, again, we're not quite ready to share the details there, on what we're thinking, but suffice it to say, we are making good progress internally on the study concept, and we're pretty excited about the way that this is taking shape and how it's mirroring the developing practice patterns for diffuse large B-cell lymphoma. So, we're still on track, I think, to share details around the time that we've guided to. So, stay tuned.

Operator (participant)

Thank you. One moment as we move to our next question. Our next question is gonna come from the line of Kelsey Goodwin with Guggenheim Securities. Your line is open. Please go ahead.

Kelsey Goodwin (VP of Biotechnology Equity Research)

... Oh, hey, good afternoon. Thanks for taking my question. I guess first, regarding the BCMA program, I guess, can you provide any kind of updates there and maybe any learnings from the assessment that you guys have been doing regarding the manufacturing process? And then maybe secondly, specific to the Notch partnership, I guess, is there any kind of qualitative update you could give or maybe some sort of timing, as you kind of work with them on the iPSC strategy? Thank you.

Zachary Roberts J. (EVP of Research and Development and CMO)

Yeah. So thanks, Kelsey, for the question. Maybe I'll take the first one, and then you can take, and David will take the Notch question. So, as far as the BCMA program goes, we are still, you know, those programs, we're not enrolling patients into the BCMA. Currently, we are still sort of examining the manufacturing process. What I can say, obviously, I won't go into specifics there, but, you know, we are learning, as I think every CAR T company is, that there are elements in the manufacturing process that are ripe for optimization. And, you know, I do think that what we are learning across our portfolio on the manufacturing side is that many times what we learn in one program can be translated into another.

We are sort of overall quite excited about the progress that we're making on understanding that manufacturing within the context of BCMA and our other clinical programs.

David Chang (President and CEO)

Kelsey, on the second question, this is David Chang. Notch Therapeutics is our partner in the iPSC area, and we've been working with them now for about 4 years. They have made a tremendous progress in, you know, differentiating the iPSC into the CD34+ stem cells, and subsequently after that, blood is differentiating into the CD8 T cells. So the progress is being made, and we're working to, you know, continuing to work very closely with Notch team to incorporate that technology into what we're doing. But, you know, given all the things that we are handling now, I think, you know, it's gonna stay at the research stage for a little bit longer.

Operator (participant)

Thank you. One moment as we move on to our next question. Our next question is going to come from the line of John Newman with Canaccord Genuity. Your line is open. Please go ahead.

John Newman (Managing Director and Senior Biotechnology Equity Research Analyst)

Hi there, and thank you for taking my question. I just wondered, for the Alpha-2 trial, you're allowing, excuse me, outpatient treatment at the investigator's discretion. I'm wondering if you expect a substantial number of patients to be treated this way. I also have a question on the enrollment, the clinical sites for the trial. I'm wondering if you've been able to open clinical sites in the EU, Canada, and Australia, where autologous CD19 CAR Ts are not as widely available or used versus the U.S. to help with enrollment. Thanks.

Zachary Roberts J. (EVP of Research and Development and CMO)

Thanks, John. So, I'll answer the second question first. So, you know, that has long been part of our strategy for enrollment, is to expand into geographies, countries, and indeed, clinical sites where autologous product is not as widely used, and that can be for many reasons, reimbursement related or access related. We're sort of encountering all kinds of different reasons why those patients are not getting access to this life-saving therapy. So in those cases, you know, having access to a clinical trial such as ALPHA2 or EXPAND really is welcomed quite heartily by the patients and by the physicians. And sorry, John, I'm blanking on your first question.

David Chang (President and CEO)

Outpatient.

Zachary Roberts J. (EVP of Research and Development and CMO)

Oh, outpatient. That's right. Thank you. Thank you, David. So we are seeing actually, you know, a fair number of patients being managed fully outpatient, and that means both the lymphodepletion as well as the CAR T infusion. It's been, I would say, very encouraging so far, and many of the centers that have met with some success in their first few patients continue to have that be their default position. Of course, if a patient needs to come in for, you know, one or more reasons, that's no problem at all. Patients can be admitted. There seems to be a high level of enthusiasm around the managing these patients outpatient.

In fact, some of the centers are actually we're having them talk to other centers to try to teach them how they are managing this. So there does seem to be quite a high level of interest to handle this outpatient.

Operator (participant)

Thank you. One moment as we move on to our next question. Our next question is going to come from the line of Kalpit Patel with B. Riley. Your line is open. Please go ahead.

Andy Fletcher (Analyst)

Good afternoon. This is Andy Fletcher on for Kalpit. Thank you for taking the questions. One of your ASH abstracts revealed the impact of a recipient's alloreactive CD8+ T cells in an allogeneic CAR T rejection. Can you please elaborate on ways that this could potentially be addressed?

Zachary Roberts J. (EVP of Research and Development and CMO)

Sure. Good question. So, you know, we've known, as I think the field has known and certainly other allogeneic CAR T developers have known that, that when you take an HLA-unmatched product from donor into a patient, that the risk of allo rejection is there. And so I think everybody is crafting these strategies around how to mitigate this host versus graft response. What I think Allogene has got that's quite exciting actually is a robust and targeted selective lymphodepletion strategy, you know, the ALLO-647 component, and when used it paired with our CD52-negative CAR T cells, that is how we have so far, I think, rather successfully managed this host versus graft reaction.

What that abstract is, is really showing is that, that this is something that we can further refine, both from an LD strategy, but also we're taking those learnings and folding them into our new product development and looking for ways to, through gene engineering or other strategies, help to prevent or mitigate that host versus graft and not relying entirely on LD. However, I would say that just what we've done so far around lymphodepletion, as our clinical data will show, is we've managed to create a great window of persistence for ourselves, where we can see high levels of expansion and persistence, and that corresponds to durable complete remission.

So I think Allogene's on the right track, but the point of that abstract is really that there's probably more that we can learn, and we're taking that forward into our new product development.

Operator (participant)

Thank you. One moment as we move on to our next question. Our next question is gonna come from the line of Sami Corwin with William Blair. Your line is open. Please go ahead.

Sami Corwin (Biotech Equity Research Analyst)

Hi. Thanks for taking my question. I noticed in the 10-Q that it was reported that there was some cases of an immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome. I was wondering if you guys could elaborate on that a little bit, and if you think it's related to the Dagger technology at all, and if that's what changed the guidance for data on the trial?

Zachary Roberts J. (EVP of Research and Development and CMO)

Thanks, Sami, for the question, and nice job with that mouthful of a new entity.

Sami Corwin (Biotech Equity Research Analyst)

Yes.

Zachary Roberts J. (EVP of Research and Development and CMO)

So, the way that we're thinking about IECHS is it's likely probably an umbrella term that has described an inflammatory process that is likely seen across CAR T products. And in fact, it's been described in both, heme, heme programs, not our heme programs, but others, as well as other solid tumor programs. And so I think when we, when we see sort of an inflammatory response, we have begun to call that IECHS, as opposed to HLH or CRS or ICANS. Sometimes this different description is a little bit more straightforward to use. So when it comes to the 316 program, you know, we just want to reiterate just how careful we want to be as we are moving through this dose escalation.

This is really, I believe, probably some of the best solid tumor data that has ever been shown for CAR T, especially for an Allo CAR T. As we are moving forward, we want to be careful that we mitigate any emergent toxicity, and so that when we get to the expansion cohorts, we have a good sense of what to expect.

Operator (participant)

Thank you. One moment as we move on to our next question. Our next question is gonna come from the line of Hartaj Singh with Oppenheimer. Your line is open. Please go ahead.

Hartaj Singh (Managing Director and Senior Equity Research Analyst)

Great, thank you. Just got a couple of questions, and thanks for all, thanks for all the updates. My question a little bit more broad. One is, you know, just on 501A, CD19 program. You know, with the move of, for example, Gilead into second line LBCL, over the last year, are you seeing sort of changes in those patients that are in third line LBCL? Are there more patients? I imagine the patient pool is probably increasing, but where is bone marrow transplant relative to that? Have things changed, you know, as those CAR T therapies have moved up, you know, earlier in lines of therapy?

And then secondly, just on a manufacturing follow-up, you know, for your lead program, are you technically in what would be a commercial material process, meaning that something that you'd be able to file your BLA with, or are you sort of still in that clinical material process? Thank you.

David Chang (President and CEO)

Yeah, hi, Josh, this is David Chang. So, let me give Zach a little bit of a break because he's been answering question after question. Your first question about, you know, 501A program and, you know, the approval of allogeneic CAR T in the earlier lines and how that's affecting our study, I think, you know, sort of taking it from that point. Certainly, this is something that we had expected as the CAR T, you know, makes a way into the earlier line, and we are seeing this both in the CD19 program, as well as, you know, as announced in today's ASH abstract, a lot of abstracts coming into the multiple myeloma with the BCMA-targeting CARs.

So, in terms of, you know, ALLO-501A ALPHA study, the fact still is that there's a large number of patients who are not getting access to the CAR T. So that segment is still open, you know, for us to tap into for the ALPHA study. And, you know, one of the reasons that we are really, you know, trying to move to the earlier line as quickly as possible is to, you know, address the, you know, this fundamental changes in the patient flow that we are witnessing in non-Hodgkin lymphoma. And, so to, you know, we are certainly expecting that kind of changes in the, in the multiple myeloma area. The second question about the manufacturing, this is something that we have worked on for a while.

Just as our CFI manufacturing facility, and it could potentially support the commercial launch. The process that we are using is really will be the basis for the commercial launch. So the answer to your question is yes.

Operator (participant)

Thank you, and one moment as we move on to our next question. Our next question is going to come from the line of Luca Issi with RBC. Your line is open. Please go ahead.

Speaker 16

Oh, great, thanks for taking our questions. This is Lisa, for Luca. Can you remind us of the timeline for when ALPHA2 and EXPAND could read out? And, if you would have sufficient runway, that would align with both of those data readouts? Thanks.

Zachary Roberts J. (EVP of Research and Development and CMO)

Yeah. So this is Zach. We are expecting our first look at the ALPHA2 data by the end of next year, and we expect to have at least some EXPAND data around the same time. So as far as the runway goes, I'll let others speak to it, but at the highest level, yes, we do have runway that would extend beyond those two data readouts.

Operator (participant)

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

David Chang (President and CEO)

Yes, and thank you for joining us today and your ongoing faith in Allogene as we create the code for Allogene CAR T. We will continue to do everything possible to validate your belief in our ability to make this a reality for patients, and look forward to sharing with you important advances across our pipeline over the coming months. Operator, you may now disconnect.

Operator (participant)

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