Allogene Therapeutics Inc (ALLO) 2023 Q2 法說會逐字稿

Hello. Thank you for standing by, and welcome to Allogene Therapeutics' Second Quarter 2023 Conference Call. (Operator Instructions) Please be aware that today's conference is being recorded. I would now like to turn the call over to Christine Cassiano, Chief Communications Officer. Ms. Cassiano, please go ahead.

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 second 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 Officer; Dr. Zachary Roberts, Executive Vice President of Research and Development and Chief Medical Officer; and Dr. Eric Schmidt, 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 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 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.

Thank you, Christine, and thank you for those joining the call today. During the second quarter, we presented updated Phase I data on our lead allogeneic CAR-T program targeting CD19 for relapse and refractory lymphoma. We are immensely proud that our off-the-shelf product candidate has shown the ability to generate durable complete responses that by all accounts appear to be similar to approved AlloCAR-T therapies. This is a significant milestone for the field and represents a great opportunity to reflect on the current state of CAR-T, including the advancement of Allogeneic options. To that end, I would like to focus my comments today on the allogeneic CAR-T field at large.

I will then ask Zach to talk specifically about our CD19 program, including reviewing the data presented in June at the American Society of Clinical Oncology, European Hematology Association and Lugano meetings. During the Q&A, we will welcome questions on other programs within our pipeline. First, let's talk about the build of cell therapy. As AlloCAR-T franchise reports increasing sales and detailed initiatives to address manufacturing constraints, some ask if there is a place for an allogeneic product. Indeed, as one of the early developers of AlloCAR-T therapy, I am proud that this modality has become a commercial success capable of changing the lives of many patients.

On the other hand, Allogeneic CAR-T products represent a fundamentally different modality with properties that are inherently more attractive than autologous CAR-T therapy and, therefore, capable of vastly changing and expanding the landscape of CAR-T access. Perhaps the most fundamental difference between the Autologous therapy and allogeneic product is that the former represents an individualized procedure that can never be manufactured at scale. As Autologous CAR-T therapies move into earlier lines, the potential patient population that is eligible for therapy will undergo dramatic expansion. And companies producing therapies at linear scale will be hard-pressed to keep up with accelerating demand.

Today, in the market for refractory lymphoma and myeloma, we are seeing that only a fraction of eligible patients can gain access to these revolutionary therapies. Potentially left out of the mix are patients who cannot really secure a manufacturing plant, patients with rapidly progressing disease for patients who cannot undergo successful collection of cells. Also, as CAR-T therapies move to earlier lines, patients now need to be referred from the community-based oncology centers to specialized CAR-T centers, which leads to yet another potential delay. By 2030, it is estimated that the number of patients with lymphoma or myeloma who will be eligible for CAR-T will grow to 300,000.

To put this figure in perspective, it is estimated that approximately 10,000 patients will receive CAR-T therapies in 2023. Several autologous providers are making large investments in manufacturing infrastructure and delivery that are designed to increase capacity. These companies are now forecasting the ability to perform as many as 10,000 individual manufacturing ones in a few years' time. But even if successful, the forecasted supply is dwarfed by the number of patients who could benefit from treatment. The unfortunate outcome is that even on the more optimistic forecast for capacity expansion, there will be far more patients without access to this modality than those who can be treated. Adding more and more linear scale manufacturing is simply not a viable model for serving an increasingly large addressable market, which will most likely lead to a sensitive market and patients without access to a potentially life-saving treatment.

My next point of reflection focuses on the innovative nature of allogeneic CAR-T products. The $1 trillion biopharmaceutical industry is based on very few therapeutic modalities. Often, new classes of drugs are met with skepticism or even disbelief. In 2012, Kite and National Cancer Institute entered into property research and development agreement or CRADA that would ultimately lead to the approval of [Dagger]. But what many forget or may not know is how many biopharmaceutical companies will first offer the same opportunity at Kite, but decline. The development of Autologous CAR-T therapies, now a multibillion-dollar industry, was a lonely endeavor. The cacophony of net payers and the development challenges that needed to be overcome required undoubted beliefs in the science. As the year progressed and wealth of data on this new modality accumulated, there was a shift in attitude towards Autologous CAR-T therapies. History doesn't repeat itself, but it often runs.

We are very excited to see progress not just from Allogene, but others who are developing allogeneic CAR-T products. We view this as a sign that the viability of the modality is becoming increasingly evident. The more companies that enter the arena with promising approaches, the more investment we see from large pharma companies, the better it is for the field. The work we have done to progress our clinical trial has allowed us to accumulate and master technology that is second to none. The learnings that must come from the Phase I trial are often hard on, but the outcomes we have seen in our recent data sets makes it clearly worthwhile and keep us excited for what is to come, a future where patients do not have to wait and fight for access to CAR-T. They can start treatment within days and without the need to undergo leukapheresis or [CAR-T] therapy. An allogeneic CAR-T product provides one, if not the only way to broaden the use of CAR-T therapy, making the delivery of therapy much easier and convenient for patients and their treating physicians.

Ultimately, I believe the convenience of an off-the-shelf allogeneic CAR-T product is the only way to introduce the potentially life-saving modality of CAR-T to a wider community setting, where the majority of earlier line patients are currently careful while preserving the potential for a one-time treatment. An off-the-shelf option that is free of the hassle and inconvenience having to return to the clinic for treatment again and again and without the cumulative toxicities that often come with lengthy chronic therapy. With that, now I would like to turn the call over to Zach.

Thank you, David. As we have noted in previous calls, some of the biggest questions facing allogeneic CAR-T development was whether the safety and efficacy of an allogeneic product to be comparable to approved autologous CAR-T therapies and perhaps even more importantly, whether an off-the-shelf product can induce durable complete remissions. At the American Society of Clinical Oncology Annual Meeting, the European Hematology Association Congress and the International Conference on Malignant Lymphoma and Lugano, we shared long-term durability data from our Phase I trial that answer these very important questions and substantially reinforced that our off-the-shelf CD19 AlloCAR-T product candidates demonstrate the promise in large B-cell lymphoma. At ASCO, with an Anacor presentation at EHA, we presented an updated analysis of the ALPHA and ALPHA2 trials focused on patients who received the regimen that is being deployed in our potentially pivotal Phase II trial.

These 12 CAR-T-naive patients with relapsed/refractory LBCL received a single dose of ALLO-501 501A manufactured using the alloy process following a lymphodepletion regimen of FCA9, which is comprised of standard low doses of fludarabine at cyclophosphamide plus 90 milligrams of AO-647. The median time from enrollment to the start of therapy was 3 days, and as of the April 20, 2023 data cutoff, all 12 patients were followed through a minimum of 6 months. 7 of 12 patients or 58% achieved a complete response in 5 patients or 42% maintain the CR through month 6. Of the 5 patients who are in CR at 6 months, 4 or 80% had an ongoing remission. The fifth patient had disease progression at 24 months. The median duration of response was 23.1 months with 3 patients remaining in remission for over 24 months and the longest remaining in remission for over 31 months.

To put these data in context, our CR rate of 58% can be viewed in light of approved Autologous CAR-T therapy CR rates that range from 32% to 54% per label. Of course, the appeal of CAR-T therapy is that complete responses can be durable. Our CR rate at month 6 of 42% compares favorably with autologous CAR-T as their rates range from 29% to approximately 40%. At the meeting in Lugano, we presented data from all 33 patients with relapsed/refractory LBCL who received ALLO-501 or 501A made using the alloy manufacturing process. In addition to the 12 patient data reported at ASCO, this data set included additional patients who received either lower doses of ALLO-647 or 2 infusions of ALLO-501 or 518 faced approximately 1 month apart in our consolidation regimen.

Across these 33 patients, 100% of patients received product for specifications, no patients received bridging therapy. In these 33 patients, ACR was achieved by 14 patients or 42% of whom 10 maintained a complete response at month 6. The median duration of response in these 33 patients was also 23.1 months, demonstrating that we could still achieve results within the parameters established by approved autologous CAR-T therapies even using less optimized dosing.

We also observed robust CAR-T cell expansion and persistence in patients, particularly in responders, arguably a first for an off-the-shelf allogeneic cell product. In all presentations, our safety analysis included all 33 CAR-T-naive LBCL patients who received alloy product. Treatment was generally well tolerated with no incidences of Grade 3 or greater CRS and no cases of high cans or GVHD. Cytopenias and infections were manageable and comparable to the experience with autologous CAR-T therapies in patients with relapsed/refractory LVCL. We showed patients neutrophilic and lymphocyte counts beginning to recover within the first month of infusion and achieving baseline levels with kinetics similar to autologous cell therapies, providing additional insight into our comparable infection rate. Our data are the first to demonstrate the potential of an allogeneic CD19 CAR-T to induce durable complete remissions and set the stage for a potentially competitive profile to approved autologous CD19 CAR-Ts.

Our focus now turns to 2 important objectives for this program. The first being enrollment in the ongoing Phase II ALPHA2 trial where we hope to definitively establish the potential of this new modality. We are very pleased to have extended enrollment in this trial into Canada and expect to begin enrolling patients in Europe in Q3 and Australia before year-end. We also continue to focus on enrollment in our Phase II EXPAND trial, which is designed to demonstrate the superiority of ALLO- 647 containing lymphodepletion regimens over a regimen of Flu/Cy alone.

In parallel, we are working through a trial design strategy that could support regulatory approval in earlier line LVCL. We believe our proposed approach may be particularly advantageous and look forward to sharing more detail on this strategy by the end of the year. We believe our success to date where others may have fallen short is attributable to our ability to support the expansion and persistence of our allogeneic CAR-T cells necessary to achieve durable tumor elimination. The preponderance of data we've already presented from our CD19 program point to an improved clinical performance when they include ALLO-647, our anti-CD52 monoclonal antibody with standard low doses of Flu/Cy.

Our platform enabled by ALLO-647, permits an extended window of CAR-T cell expansion and persistence. What ALLO-647 does cannot be reproduced even with high doses of chemotherapy that might be associated with severe toxicity. We are now focused on applying a rigorous approach to explore the boundaries of what works to the best practice to enrich our understanding of CAR-T cell expansion and persistence as we investigate next-generation technologies, including Dagger, which is currently being utilized in our ALLO-316 anti-CD70 solid tumor trial. I will now turn the call over to Eric.

Thank you, Zach, and good afternoon, everyone. I'd like to begin by acknowledging that today is my last day at Allogene, a very bittersweet occasion. The past 5 years have been rewarding, exciting and fun. They provided new challenges, allowed me to build life-changing relationships and perhaps most intriguingly opened my eyes to a side of the industry that I could not have previously fathomed. I respect for what management teams must do and the complexity of decision-making and drug development have grown exponentially. It has truly been a privilege to serve as the CFO of Allogene. I look forward to spending more time in New York with my family.

Allogene will forever be a part of me. I am thankful to David and the team for the trust and the opportunity they have accorded me and look forward to following the company's progress as it turns to the promise of AlloCAR-T into a reality for patients. Now on to our financials. I'm pleased to share that our balance sheet remains very healthy. We ended June 30, 2023, with $544.5 million in cash, cash equivalents and investments. In addition to our efforts to ensure operational efficiency, we raised net proceeds of approximately $88 million in the second quarter from our at-the-market or ATM equity financing facility. Based on our current expectations, we believe we have extended our cash runway into the second half of 2025.

In the second quarter of 2023, our research and development expenses were $62.0 million, which includes $6.9 million of non-cash stock-based compensation expense. General and administrative expenses were $18.5 million for the second quarter of 2023, which includes $9.7 million of non-cash stock-based compensation expense. Our net loss for the second quarter of 2023 was $78.0 million or $0.53 per share, including non-cash stock-based compensation expense of $16.6 million. We continue to expect a decrease in cash, cash equivalents and investments of approximately $230 million in 2023. We expect our 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 Instructions) Our first question comes from the line of Tyler Van Buren with TD Cowen.

Great. Congratulations, Eric, on all that you helped the company achieve during your tenure at Allogene. With that said, my question is, I'd like to ask you to elaborate on the pace of enrollment in ALPHA2 and whether you've seen an increase in the pace of enrollment, especially with all the recent conference presentations.

Tyler, it's Zach. Thanks for the question. So the guidance that we have provided is that we expect to complete enrollment in the first half of next year. We're maintaining that guidance today. I think the pace of enrollment is going to change over time, and we always expect to see enrollment pick up towards the end of the enrollment period that is very standard for clinical trials. Additionally, we have gotten approval by the EMA to open sites in Europe, and we expect to do that in the coming weeks. And furthermore, plan to add Australia to the roster of enrolling sites by the end of the year. So all signs are pointing in the direction of momentum building in terms of geographies coming online, and we expect to have the study enrolled in the first half.

Our next question comes from the line of Salveen Richter with Goldman Sachs.

This is Anna [Medon] for Salveen. Just a 2-part question from us. As you clearly described in the prepared remarks, it seems like the supply situation with Autologous CAR-T is improving, especially with respect to BCMA CAR-T. I guess in this context, how are you thinking about the competitive landscape given the ongoing optimization that's required for ALLO-715? And then in the lymphoma space, in the context of the recent data that was presented from Caribou CD19 program, which is also starting to evaluate the asset in earlier line patients.

Yes. This is David Chang. Let me take the first question on the BCMA and I'll ask Zach to comment on the competitive data. In terms of the Autologous CAR-T supply, I mean we are definitely hearing what you're hearing is that pharma that in this space is putting a lot of effort to increase the manufacturing capacity. And along with that, I think there has been some improvement in reducing the out-of-spec, which also leads to not being able to provide commercial materials to patients. I mean, certainly, that is happening, and we were expecting that to happen.

But the pace of that is how it's happening as we are following is as expected. There will be a lot of ramp-up time that's needed. Now that leads to, I think, what you are really asking about our BCMA program, we are continuing to look for the opportunity to improve the manufacturing process. Certainly, we always knew that manufacturing is one of the key components of making the cell product viable and also maintaining the level of efficacy that we are hoping to do. So we're making good progress, and we are continuously reviewing what we will be doing with the BCMA program as we complete the manufacturing review. Zach on the CD19?

Yes. So a great question about the Caribou update. Overall, we were very pleased to see another sponsor, present data supporting the use of ALPHA beta T cells in an off-the-shelf allogeneic platform and driving benefit for patients. We see that this is a very validating milestone for the field. And having been at this now for 5 years and arguably some of the most experience in this field. We are very proud to see an additional person join this field, but we also stand very much by the data that we presented this summer as part of the overall and growing experience in off-the-shelf AlloCAR-T cells.

Our next question comes from the line of Michael Yee with Jefferies.

One of the things that comes up is the use of CAR-T after Yescarta. And since there's uncertainties about that, one could envision that your product would be an obvious fit earlier lines, particularly given off the shelf. To do that, you would need to run a second-line study. You suggested you would give us some tidbits and some insight into how you would think about a design for that later this year. But can you just remind us, could you actually start a second-line study next year? Are there things relevant to having to make progress on third line? Would you have the money to do that? Could a pharma company help you out a lot easier? Maybe just talk through the different challenges of second line, how you should think about that because I think that's even more important than third line.

Mike, let me take the first part of the question. You were asking all important and excellent questions. And I'll ask Zach to comment on the study design, which is very much on track. In terms of the earlier line, I think that's really the opportunity of the South therapy to maximize the benefit of one-time treatment that can potentially lead to something that's similar to cure where successfully treated patients no longer requires a second, third or subsequent lines of therapy. That is really in the holy grail of what we are trying to do in the oncology space.

And when we think about how the patients are cared for in the earlier line setting as well as – what I mean by that is most of these patients are careful, not in the tertiary centers, but in the local oncology infusion clinics and local-oncologists. And so this is where we also see the benefit of off-the-shelf allogeneic CAR-T really shining. And that's where we are trying to march as we think about our CD19 program beyond the current refractory and relapsed setting in the third-line setting. Previously, we've been guiding that we will work with the investigator to finalize the study design, get regulatory input from the agencies and then look for launching the study sometime in 2024. That plan still holds. In terms of study design, let me ask Zach to comment on that.

It's very early, but yes, thanks, Mike, for the question. So I think the premise of it is spot on. I think you look across CD19 and also BCMA. And what we're learning is that for as powerful as these therapies are in relapsed/refractory disease, their utility in earlier lines is as compelling, if not more so. And obviously, the numbers of patients are greater there. So we've been keenly focused on coming up with a study design in earlier lines that I think will play to our strengths and also serve an unmet need that exists in that second line. And we're not quite ready yet to share a lot of details on this study. We hope to be able to do that by the end of this year. But suffice it to say, we think that this is a great opportunity for the field and for Allogene in particular. Thank you.

Our next question comes from the line of Brian Cheng with JPMorgan.

You mentioned that you're thinking of exploring combining CAR with the Dagger technology in hem and solid tumors. Just as you need to be efficient on resources since most of your focus today is now on CD19. How does the potential exploration strategy fit into your current portfolio and timing for the next set of tiles? Is this more of a BD play?

Brian, Dave Chang here. Today, I mean, you guys are really asking excellent questions. When we think about the allogeneic, and I think this is something that we can say for the cell therapy as a whole. This is still very early stages of cell therapy we are in right now. And the potential of cell therapy is ability to engineer the CAR-T cells, in this case, through the available technology, whether it's antiviral gene transaction, and that's essentially what the autologous cell therapy players are doing to how the field has evolved to include gene editing, possibly multistep gene engineering, including site-specific integration, et cetera, et cetera. And that's really the holy grail of cell therapy that not just us, everybody in the allogeneic cell field is trying to accomplish.

So in that context, we don't necessarily see the programs that we are advancing as the answer to all the solutions that we are trying to provide and advance this field. Some of the things that we internally discuss is not just how to make the cells work better, but also can we potentially reduce the lymphodepletion, make the turkey more easier to administer than outpatient, all these questions. And that's where the concept of next-generation such as the Dagger technology comes in. The question about how much can we do in the current environment where the spending is highly scrutinized is a very good one. Mike was asking the same question. And this is something that we are trying to address through the prioritization as well as trying to do things as efficiently. And also, this is another -- in a situation where any kind of partnership could further accelerate what we are trying to do by bringing additional resources as well as capabilities that we may not necessarily have at this point.

Our next question comes from the line of Michael Schmidt with Guggenheim.

This is Kelsey on for Michael. Congrats, Eric, on your last day, but sad to see you go. I just had a couple of quick questions. I guess, first, building on your prepared remarks, David. There's a small percentage of eligible patients actually getting CAR-T, and we hear a lot about capacity, specifically in myeloma, of course, because they're early in the launches. But I guess for DLBCL, is capacity still the biggest limiting factor? Or is it something else? And then maybe building on that last question, how does the Notch partnership fit into the stricter capital allocation?

Yes, the question about what's happening in autologous. I think truthfully, we follow what the large companies in this space released the information in the quarterly basis. So you know as much information as we do. The bottom line is by the estimate that some of the pharma that in the CAR-T space I'm making is that in the third-line setting, only about 30% of the eligible patients are receiving CAR-T therapy. That remark was made in 2022. Now in 2023, there may have been some uptick on the percentage of eligible patients who are getting the CAR-T. And we are also looking in terms of the quarterly earnings release and how much the revenue has gone up and trying to triangulate how much of that is due to earlier line usage versus further penetration in the third line.

On top of that, we talk not only with CAR-T experts, but also other hemato-oncologists, especially at the centers that do not have access to the commercial CAR-T. But let's be reminded CAR-T is only using the certified centers and the number of certified centers that can administer commercial supply is still limited. So my comment as well as the answer to your question, it's somewhat of a guesswork as well, but our current estimate is that there is a still a sufficient number in a large number of patients who are eligible who are not getting access to the CAR-T in the non-Hodgkin's lymphoma space. The second part of the question with the notch and what we are doing.

I mean, Notch is doing something incredible, trying to differentiate the iPSC cells into functioning T cells that really has been the holy grail of what the field may be able to do, leveraging the power of iPSC. We are sensitive in terms of time horizon, but that technology can really be scaled up and be realistic in terms of introducing the clinics. And this is an area that I'm always humbled by how difficult it is. Back in 2015, 2016, I thought in the next 7 to 10 years, iPSC will be more or less in the mainstay of the CAR-T. We have about 10 years from that time. And still, I think it's several years before the IPS-derived CAR-T therapy can be in the clinics. I mean the future is definitely there, but I think it's just taking a time, and we are definitely putting that in the context of how we are partnering and working with Notch.

Our next question comes from the line of John Newman with Canaccord.

So you mentioned that you're going to be enrolling patients in the pivotal study in Europe and Australia here, I think Europe shortly in Australia by the end of the year. I'm curious if you could talk about whether or not there's any difference in the availability of the autologous CAR-T therapies there. What I'm asking the question is I'm just wondering if perhaps enrolling patients in those 2 regions could really increase the chances that you're getting patients that would otherwise be getting autologous therapies.

Yes. So we know that the utilization of CAR-T generally in those regions is significantly less common than it is in the United States. And obviously, we expect that over time, that will change. And as additional pivotal data sets come to the table and regulators begin to approve these therapies and payers get on board as well. The whole field is moving towards utilization of CAR-T in third line and in second line. But these regions are significantly behind the United States. So there are plenty of patients in both of those regions where the unmet need in third line is substantially higher than in the United States. So we feel that it and have felt for a long time that it's made a lot of sense to broaden the footprint and be able to bring on those patients whose neither not being met by current standards in those ex-U.S. regions.

Our next question comes from the line of Jack Allen with Baird.

Great. Congratulations to the team on the progress. And Eric, congratulations to you on all of your accomplishments over the last 5 years. I'm going to try to do my best to put you to work on your last day here, and I wanted to talk for a second about the Servier relationship. Could you remind us maybe how things stand as it relates to Servier? And I'm seeing in the 10-K that the 10-Q that you received very de minimis payments from Citi in the last couple of quarters here. Do you expect that those payments could be higher as you move into the European region with the ALPHA2 study? And what's baked in as it relates to the cash-only guidance surrounding Servier, the relationship there?

Yes. Thank you very much for the kind personal comments and the question. It's good to hear your voice. And I think you must have studied more French than I did in high school because your pronunciation of Servier is spot on. We continue to have a little bit of a challenging relationship with Servier, as we've discussed previously and in our SEC filings. There are disputes over certain aspects of our collaboration. As you noted, there are disputes over cost recoveries, which we believe we're entitled to as well as our ability to opt into ex-U.S. development in the future date. So at this point in time, rather than to delve into legal matters, I'll just lead it to what's going to be published in our 10-Q in terms of the update. And hopefully, we'll be able to find an eligible solution going forward.

Our next question comes from the line of Asthika Goonewardene with Truist.

This is Karina for Asthika. I had a question on ALLO-715. I know you guys are looking -- just wanted to know if you guys are looking to change the cytokines used culture days to get a more nascent cell phenotype? And are you trying to get more of a carbon efficacy? If you can share some color on tighter guidance on the timing as well, that would be great.

Yes, Karina, there are multiple things that we are doing with the manufacturing process review. And as your question has pointed out, cytokine is an important aspect of what we are reviewing without going into further details. And in terms of timeline of what we will say about our BCMA program, let's defer that until we complete the review and decide when we will think about introducing back into the clinic.

Our next question comes from the line of Kalpit Patel with B. Riley.

One more on the enrollment. Could you please comment on how many additional clinical sites do you expect to include for the EXPAND trial? And is the guidance still unchanged to report data roughly around the same time from this study as with the ALPHA2 study?

Yes. Thank you for the question. So we haven't gone into exact in detail on the number of sites for either ALPHA2 and EXPAND. We are continuing to bring on sites in North America for EXPAND. As you know, this is a relatively newer trial than ALPHA2. So we didn't have the benefit of long-standing relationships with Phase I sites there, so everything is starting from scratch. But sites are coming online as we speak. And similar to the plan for ALPHA2, we also intend to bring -- expand into both EU and Australia. And the last point that you asked about is still correct. Yes, we do expect to have data for EXPAND coming at roughly the same time as ALPHA2.

Our next question comes from the line of Sami Corwin with William Blair.

Given that the current commercial CAR-T therapies are commercialized by large pharma players or through partnerships with large pharma. I guess, are you thinking about commercializing ALPHA-501 alone? Or do you think you'll need a commercial part?

Yes, Sami, let me take that. Great question. I mean, that's something that we are internally discussing. And I think once we furthered the position and how we're going to commercialize, we will share that information. But I think it's a little bit too early for us to say one way or the other.

Our next question comes from the line of Luca Issi with RBC Capital.

Maybe Zach, if I may circle back on a prior question, can you just talk a little bit about your enrollment projections for Alpha2 versus EXPAND? What gives you confidence if you can complete enrollment of both trials in the first half of 2024? It feels some enrolling, expanding much harder than enrolling ALPHA2. I would love to hear thoughts on that. And then Eric, thanks again for all your help and all the best in your next chapter.

Thanks, Luca, for the question. This is Zach. So the enrollment of each study is ongoing currently, as we've said, we've guided to completion of enrollment of ALPHA2 by the first half of next year. We actually haven't specified exactly when we expect to expand the complete enrollment. But based on the study designs of these 2 trials, our current projections are that between the fewer patients that are required to enroll and expand as well as our belief that the endpoint will actually take less time to come about with that study that we do think that those data sets will be available at roughly the same time.

Our next question comes from the line of Tony Butler with E.F. Hutton.

David or Zach, I wanted to go back to Dagger, if I may. I understand that there is a diagnostic being employed at this time. The question is in Dr. [Sauers] presentation at AACR, I don't believe any patients had -- or there wasn't any data available for patients who are given 240 million cells. And the question is, or can you address whether there has been that dosing that has occurred in a number of patients? And number 2 is the data for efficacy. I'm not asking about, but what I am asking, it's possible for you to make any statements because the data was in my opinion, so we're so good and the side effect profile was very consistent with other studies. But importantly, they're minimal fatigue in syncopy and/or minimal CRS as was demonstrated at the lower doses. And finally, Eric, thank you very much, and again, publicly all the best.

Thank you for the question. So as we said at AACR and is still true today, we are continuing with the dose-finding, dose exploration part of this trial. I don't want to get into details about how many patients have been treated at each dose beyond what has been shared publicly at AACR. We do expect to be able to share additional information from this trial later on, and we're continuing the enrollment now. And other than that, though, I very much agree with your assessment that the data that we shared at AACR certainly is compelling and superior to what these patients could expect from standard of care.

Our next question comes from the line of Hartaj Singh with Oppenheimer.

Great. And also a good luck, Eric, I have not known you, but best of luck. The question I have is just when you read out ALPHA2 later in 2024, I was just wondering what's out there in terms of a comparison? Or what are you looking for that give you comfort in your discussion with the FDA to enable BLA-looking activity, be it enabling activities, whether it's response rates and duration of response? I mean, what's the ballpark figures you're thinking about or that would make you comfortable? And then just a minor follow-up to a previous question, which is that are you dosing patients ALPHA2 from your commercial facility?

Thanks for the question. So maybe I'll take the first one. So I think primarily, what's giving us comfort about the Phase II program is all of the experience that we have from Phase I, which was really, again, brought to the surface in June at the various conferences where we share data feedback there and since it's been overwhelmingly positive from investigators, both those that are involved in the trial and those that are not. And so those are in patients that meet the eligibility criteria for our Phase II program. And so that's our view going forward. And I don't want to get into specifics about conversations with FDA, but we think that this is filling a much-needed niche in the landscape currently given all of the access limitations that David alluded to previously in the prepared remarks. Maybe, David, I'll hand it to you for the commercial facility question.

Yes. So the second question is about patient dosing. As we have previously communicated, the patients are currently in dose from the materials that our contract manufacturer has produced in the way that we have treated the patients in the Phase I study.

Our next question comes from the line of Kishore Gangangari with JMP Securities.

This is Ren Benjamin. Can you hear me? I don't know where the guy Kishore from. But Eric, all the best in your future endeavors. The question that I have has to do with ALLO-316. I view that as the next main value driver and driver of shareholder value. I'm curious, as you're looking at the in vitro companion diagnostic, can you provide a little bit more color regarding this, how invasive is the process? Are you identifying patients in the real world that's different than what you might have predicted from demonological studies? And I guess, finally, you expect dose escalation to complete by the end of 2023. But how many patients do you think you'll have by the end of the year?

So the first question on the companion diagnostic, I can tell you that it is not -- I mean, it's a biopsy, but we're allowing biopsies that were taken prior to study enrollment for evaluation. So some patients are requiring fresh biopsies if there's no prior material that is accessible, but many others are just giving us blocks from their original diagnosis or a recent operation of biopsy. So in that regard, it's no more invasive than any other tissue assessment that occurs every day in oncology.

And then the second part of that question was, are we seeing differences in the results of these tests and what we'd have expected from the literature? The answer to that question is no. What we're finding is very consistent with the literature. So there's been no surprises there. As far as the second question, the number of patients, again, I don't want to get too into the weeds here on what setting expectations for the future updates. But the interest in this program is very high, and that was, again, spiked after the ACR presentation. It's remained high ever since. And so there's been an abundance of patients who are interested in abundance of investigators who are interested in putting patients onto the trial.

Our next question comes from the line of Jason Gerberry with Bank of America Securities.

Just a question for David. I wanted to come back to earlier comments just about the challenges of Autologous CAR-T space and early scaling manufacturing. And I really wanted to get your perspective on what you see as the biggest impediment in the autologous approaches moving forward with like decentralized Quantose model, which is being explored by companies like Galapagos. So what do you see as the biggest hurdle to operationalizing that and scaling.

Yes, great question. I do have same questions, exact questions that you are asking. Obviously, I have to respect how different companies are thinking about to advance autologous cell therapy and the quick manufacturing or point-of-care manufacturing sometimes comes up. Obviously, these are early days, and I don't have a clear picture about how that's going to play out. But when you think about autologous cell therapy, there are multiple dimensions. One is it has to be manufactured one at a time. Patients have to undergo leukapheresis. And as well as the waiting like any other products that are used in human, all the release test that has to be part of the manufacturing process before the product can be used in humans. And I think all these things provides, in my view, somewhat of a barrier to really realize the full potential of the CAR-T therapy, and that's where the value proposition of the allogeneic cell therapy is coming.

Our next question comes from the line of William Pickering with Bernstein.

In your ALPHA2 study, how much outpatient dosing have you seen so far in the trial? And what are your expectations for how common that might potentially be in a commercial setting? And if I can maybe just ask one more. What are your expectations for the time horizon for an allogeneic therapy to be rolled out at hospitals that don't administer autologous CAR-T today, such as a community hospital, basically trying to understand when you might be able to access some of these market segments where you're not competing head-to-head with autologous?

Will, great question. In terms of our patient dosing, the ongoing studies to allow that. At this point, as we treat more patients, we will be able to provide more information, but I think it's relatively too early. And in terms of the second question about allogeneic in the patient setting and all that, I think that's the direction that we want to take our programs to. So at this point, it's still early, so stay tuned.

Our next question comes from the line of Ben Burnett with Stifel.

This is Carolina Ibanez on for Ben Burnett. A follow-up on the in vitro companion diagnostic, you have designed for ALLO-316. You mentioned that this tissue-based. Is this IHC-type assay? And wondering if you are planning to come back a centralized diagnostic assessment. And would appreciate also if you can talk to how you plan to account for heterogeneity in CD70 expression.

So it is an IHC-based assay. And so it does give us an opportunity to address and understand and score the heterogeneity. So we've taken that into account and the development of the assay.

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

Thank you very much for joining our call today. We are thrilled that our off-the-shelf CD19 AlloCAR-T data continues to demonstrate both great promise in hematologic cancers, and we remain focused on advancing the industry's first potentially pivotal allogeneic CAR-T trial in order to enable more patients to access CAR-T. Operator, you may now disconnect.

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.