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spk11: Hello, and thank you for standing by. Welcome to Allergy and Therapeutics' second quarter 2024 conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask the question during this session, you will need to press star 11 on your telephone. You will then hear an automatic message advising your hand is raised. To withdraw your question, please press star 11 again. I would now like to turn the call over to Christine Cassiana. You may begin.
spk10: Thank you, operator, and welcome to all who have joined this call. After the market closed today, Allergy issued a press release that provides a business update and financial results for the second quarter of 2024. This press release and today's webcast are available on our website. Following our prepared remarks, we will host a Q&A session. We recognize that historically questions have been multifaceted, but note that we will endeavor to keep this call to under an hour. 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. These may include statements regarding the success and timing of our ongoing and planned clinical trials, data presentations, regulatory filings, future research and development efforts, manufacturing capabilities, the safety and efficacy of our product candidates, commercial market forecasts, and 2024 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 the potential risks can be found in our press release and latest SEC disclosure documents. You are cautioned not to place undue reliance on these forward-looking statements, and Allogene disclaims any obligation to update these statements. I'll now turn the call over to David.
spk16: Thank you, Christine, and welcome to those on the call today. We hope you've all enjoyed a pleasant summer so far. As I think about the first half of 2024 for Allergen, the word that continually comes to mind is momentum. Early in 2024, we reset the clinical development plan by advancing Semacel, our lead CD19 Allocard T product, into an LBCL first-line consolidation study and announced our decision to develop and advance our next-generation Allocard T product, Allo329, into autoimmune indications, thereby placing Allogen in an enviable position of having clinical programs in heme malignancies, solid tumors, and autoimmune indications. Hard work creates opportunities, but external factors must line up to create and build momentum. As we think about the two programs, we get asked about most often, alpha-3 with semicell and allo-329 in autoimmune. Momentum is on our side. To be clear, This does not mean that it has been easy. Our team is working harder than ever. But that same hard work and dedication, along with the bold choices we've made over the last year, set off a chain reaction that we see daily as we work with investigators and external stakeholders on our programs. Simply put, the reset that was based on our longstanding conviction on our Alucard T programs have put us in a position to potentially change the CAR-T landscape. Momentum for us is merely a starting point. Now that we have shifted strategy into a clear and honorable leadership position, our programs continue to build speed, and it has been remarkable for our lead program, Alpha 3. I will spotlight three measures that may not be as visible to investors as they are to us internally at Allergen. First, while the market is not kind to biotech right now, we strengthened our base of investors in this last round with some of the highest caliber investors any company could hope for. We don't take that for granted. The number of sites who want to participate in our Alpha 3 trial and the energy with which they are engaged can be likened to what we saw in the early days of OTALIS-CAR-T. There seems to be undercurrent of understanding that this trial has the potential to forever change their practices. Third, the collaborative engagement from the FDA on this trial has been illuminating. We believe we have achieved support for Alpha-3 based on three key benefits that stem from the innovative study design. One, advancing CAR-T into earlier line setting maximizes the curative potential of the virality. Two, treating minimum residual disease, or MRD, the lowest disease volume one can measure, has the potential to make CAR-T safer and more effective. Using MRD to select and treat only the patient who will likely experience recurrence makes Alpha-3 design very efficient, concentrating treatment in only the patient population who needs it and leaving everybody else alone. We believe these key points are well aligned with the views of FDA and other key stakeholders. We aim to validate the support for this trial. We have also continued to strengthen allergens, even if not in the spotlight or something that garners headlines, to ensure that we can deliver on our promises, such as the work done in our South Forge One facility in the East Bay, where we now manufacture all of our CAR-T investigational products. This significantly minimizes our reliance on contract manufacturers for the products and provides allergens with a critical strategic asset, the manufacturing capacity to serve the market that we are addressing in our trials. As the months continue, I am confident that this exceptional momentum we feel internally will become increasingly evident to the outside world. I will now turn the call over to Zach to discuss the programs of most significant interest to investors.
spk04: Thank you, David. As most of you know, our development focus in 2024 has been on our four core programs, semicell for first-line consolidation in LBCL and relapsed refractory CLL, allo329 in autoimmune, and allo316 in renal cell carcinoma. While our CLL and renal cell programs continue to move forward as planned, with a meaningful update from the RCC trial planned by year-end, I will focus my remarks today on the two programs that we get most asked about. Semicel in first-line consolidation, and Allo329 in autoimmune disease. I'll start with our lead program, Semicel and the Alpha-3 trial, which we initiated in June. In just a few weeks following the Investigational Device Exemption, or IDE, approval in mid-June, we've opened the first 10 community and academic cancer centers and have been successfully screening patients. The speed with which we've been able to bring community cancer centers into the trial, in particular, speaks volumes for what this may mean commercially, and reinforces our belief that an allogeneic CAR-T option will be what opens the door to this modality for these centers where most patients are treated. First-line chemoimmunotherapy for LBCL has largely gone unchanged for a quarter century, and for good reason. ARCHOP and similar regimens work pretty well, with the majority of patients achieving cure with this easy-to-give, safe regimen. However, approximately one-third of patients with LBCL whose disease initially responds to RCHOP will experience relapse. Alpha-3 is a groundbreaking trial for two reasons. First, it is the first prospective trial that will utilize an ultra-sensitive biomarker to inform physicians and patients whether the cancer is likely cured by first-line RCHOP or if the disease will likely recur and require second-line treatment or beyond. And second, Alpha-3 is the first trial to propose a treatment, namely a dose of semicell for remission consolidation, specifically for those patients who are likely to face a future relapse. If positive, Alpha-3 could mark the beginning of a new era in LBCL treatment, potentially supplanting the current standard of care after frontline treatment, which has for decades been to watch and wait for the disease to relapse. We believe our partnership with Foresight Diagnostics, who is developing a novel and potentially practice-changing test for minimal residual disease, will change that. This investigational test, when administered following the completion of frontline treatment for LBCL, has the potential to offer a highly accurate prediction of future disease relapses. Alpha-3, therefore, offers something to all patients who screen. If the screening MRD test is positive, you are potentially eligible to receive a dose of CAR T cells designed to eradicate the residual disease, hopefully attaining the cure which remained elusive after RCHOP. If the screening MRD test is negative, it could provide assurance that your disease has been fully cured. Peace of mind after a life-altering diagnosis and its treatment cannot be underestimated. Importantly, Alpha-3 builds on the growing understanding that administering CAR-T therapies to patients with low disease burden can improve safety and efficacy outcomes. The industry has presented research that illustrates this point. Semicel's Phase I safety profile with low rates of CRS and ICANS already permits its use in the outpatient setting in relapsed refractory patients and may further improve in patients with no radiological evidence of disease. Combine this with the elimination of complex logistics that have hindered CAR-T adoption, as well as the reliance on referrals, And we have, as David rightly noted, a clear momentum effect for the Alpha-3 trial with investigators. As we have noted in previous calls, the outcome of this pivotal trial could allow semacell to be embedded in the first-line setting where autologous therapies are far less feasible. Consolidating response with an MRD-positive result post-RCHOP requires immediate and definitive action to prevent an impending relapse. Relapses tend to occur quickly after completion of our CHOP, in many cases within weeks to a few months, making the speed to treatment a critical factor in the success of a consolidation strategy like Alpha-3. We bring to the table a truly differentiated CAR-T offering that has the potential to break open an untapped market. Few can say that. The first indication of how the trial is proceeding will be when we announce the selection of the lymphodepletion regimen, we will continue to the end of the trial. That announcement is expected in mid-2025. The next study milestones will come less than a year later. We expect to complete enrollment in the first half of 2026. The prognosis for patients who are MRD positive at the end of frontline therapy is quite poor, so study events are expected to come in quickly. Therefore, we expect to perform efficacy analyses in 2026 as well. This will include an independent Data Safety Monitoring Board interim efficacy analysis in the first half of 2026 and the data readout of the primary analysis year-end 2026. If the trial is successful, we expect to follow these data readouts with a biologics license application submission in 2027. I'll now discuss ALLO 329. Differentiation is critical across our core programs. We declared our move into the autoimmune space with the goal of resetting the immune system with a single infusion. Allo329, our next generation CD19-CD70 dual CAR, incorporates our Dagger technology, CRISPR-based gene editing, and site-specific CAR transgene integration, and is rationally designed to meet the unique needs of patients with autoimmune disease. Our Dagger technology provides a potential path to reducing or eliminating lymphodepletion which we believe may create more development and commercial opportunities for allo329 in autoimmune indications. We are on track to file an IND in Q1 of 2025 and open the trial to enrollment by mid-2025. As a result, we expect to have proof of concept in this trial by the end of 2025. We recognize that highest clinical proof of concept is in lupus, but we also know the importance of differentiation. And the path we are taking provides us the luxury of time to define the best approach while leveraging proof of concept data from other trials to consider other indications with unmet needs. We expect to provide more detail on our development plan by the end of the year and appreciate the feedback many of you have provided as we chart this course. I'll now turn the call over to Jeff to review our latest financials.
spk05: Thank you, Zach. Before I dive into the financials, I'd like to express my appreciation to the investors who continue to demonstrate their support for our work. I know this market makes it a challenge, but I assure you we do not take that support for granted. I could not agree more with David and Zach. The momentum we have at Allogene is palpable, and we believe it will soon be equally evident to the market. Allogene is in a unique position. We control the only clinically validated allogeneic CD19 CAR T product positioned to transform how and where CAR Ts are used in heme malignancies. The recognition for this will only grow over the next 6 to 12 months as the Alpha 3 program is de-risked. Let me now turn to our financial highlights. Our cash balance as of the end of Q2 2024 was $444.6 million in cash, cash equivalents, and investments. And we reiterate that our cash runway extends into the second half of 2026. Q2 2024 research and development expenses were $50.4 million, which includes $5.3 million in expenses associated with non-cash stock-based compensation. General and administrative expenses in Q2 were $16.1 million, which includes $8.2 million of non-cash stock-based compensation expense. For Q2 2024, our net loss was $66.4 million, or 35 cents per share, including non-cash stock-based compensation expense of $13.6 million, and $5 million in non-cash impairment of long-lived asset expense. For 2024, we continue to expect a cash burn of approximately $200 million, We expect full year 2024 GAAP operating expenses to be approximately $300 million, which includes estimated non-cash stock-based compensation expense of approximately $60 million. This guidance excludes any impact from potential business development activities. We'll now open the call for questions.
spk11: Thank you. Ladies and gentlemen, to ask the question, please press star 11 on your telephone. and then wait to hear your name announced. To withdraw your question, please press star 11 again. We ask that you limit yourself to one question per caller. Please stand by while we compile the Q&A roster. Our first question comes from the line of Salveen Richter with Goldman Sachs. Your line is open. Hi, this is Lydia on for Salveen.
spk09: Thanks so much for taking our question. Just on semacell in the frontline consolidation setting, could you speak to any gating factors that might prevent a patient, an MRD-positive patient, from opting for semacell? And are there any clinical preferences that you're hearing from KOLs or a setting where this might not be recommended? Thank you so much.
spk04: Hi, Lydia. This is Zach. Thanks for the question. So if I understood it correctly, you're asking about what what a patient may decide if they come back MRD positive, whether Alpha-3 is the right study for them or not. So, right now, there are no real alternatives for patients who come back MRD positive. There are no approved second-line therapies for patients who are in remission, even if they have an MRD positive result. The only option that they currently have would be in the context of a clinical trial. And the only clinical trial that currently is open for patients who have an MRD-positive result at the end of therapy is Alpha-3. So it should be a fairly straightforward decision for patients.
spk11: Thank you. Will you stand by for our next question? Our next question comes from the line of Brian Ching with J.P. Morgan. Your line is open.
spk00: Hey, guys. Thanks for taking our question today. Maybe just two on Alpha 3. Can you provide some early initial metric on the screenout rate on MRD positivity? Is it in line with our expectation? And then on the supply side, I just want to follow up on your remarks related to the Cell Force 1 facility. Can you confirm whether the supply now is actively coming from the Cell Force 1 for the Alpha 3? And then I have one quick follow-up. Thank you.
spk16: Hey, Brian. This is David Chang. I'll take both of those questions. With respect to the early metrics that we are following for the Alpha 3 study, I mean, you know, we started the study, and as we have made a comment in the prepared statement, you know, there are 10 active sites that are sending patients for screening and enrollment. The metrics that we follow, I mean, certainly, you know, there are internal ones, but I would consider that these are very standard metrics that any clinical operations team would follow, so there's not anything unique. As the study progresses a little bit more, you know, we will be able to provide some information in regards to, you know, the MRD positive rate and things like that, but right now it's too early to comment on that. The second one, the response is pretty easy. With the ongoing studies, especially the Alpha-3 study, which is what the study that you are referring to, yes, the clinical material for the Alpha-3 is coming from the CF1-manufactured semicell.
spk00: Okay. And then maybe just curious on your thoughts around the, because we saw recently a relapse case with an autologous CD19 CAR T program out of ULAR back in June. Just curious what your thoughts are on that data set, and does that have any impact on how you think about your dosing or lymphodepletion regimen for 329? Thanks for taking our questions.
spk16: Yeah, so that's sort of an added question. I think that is referring to the autologous CD19 CAR T being studied in autoimmune indications. You know, the way we view is that, you know, still there's a lot going on with the signal finding and, you know, the proof of concept data being generated. As that happens, you know, there will be some, you know, variability. I don't think, you know, the recent findings as reported at EULA, it doesn't really change any assumptions around what the CAR T30 can do in the autoimmune indications. You know, what we are seeing, you know, fundamentally is very different than all other treatment that has gone forward in the autoimmune indication. You know, specifically the, you know, potential of being able to provide long-term remission after single infusion, that is very attractive. The duration of long-term remission, I think that's what's coming into question, and what is the length of remission that would really make us to get excited about. I think that is something that we are following closely, but most of the patients who have been treated with the autologous CD19 CAR-T and also with some other BCMA CAR-T, what we are seeing is that the durability of response is very good, lasting a year or longer, and sometimes ongoing response as the last data cuts. So it really doesn't change any of the assumptions that we are making with our ALLO3-9. which as an allogeneic CAR T provides a lot more benefit that will be important as we think about the autoimmune indications.
spk11: Thank you. Will you stand by for our next question? Our next question comes from the line of Michael Yee with Jefferies. Your line is open.
spk08: Hi, thanks for taking our questions. This is Jen Ali for Mike at Jefferies, and congrats on getting the Alpha-3 trial started. Would you be able to comment on the pace of ramp up for more sites, particularly thinking about leveraging the old sites that you had for alpha study and branching out to newer sites and balancing academic versus community and where the less severe frontline patients may be based at? Thank you.
spk04: Hi, this is Zach. So great question. And so the approach that we are taking is, I would say, both similar and distinct from what we've taken in the later line studies that we've had ongoing for a few years at Allogene. As you rightly point out in your question, the target population that we are pursuing in Alpha 3, for the most part, are treated in the community. There are some patients who do get treated at large academic centers, either from the outset or through referral. but up to about 80% of patients with frontline or newly diagnosed LBCL are treated in the community. That fact alone has really guided our decision-making around site selection. And so, as we mentioned in the prepared remarks and as reflected on clinicaltrials.gov, the early wave of studies that have activated or of sites that have activated in this study have indeed been community centers, which are the common centers for frontline care. That said, the large academic referral centers are always going to have a role to play in clinical trial execution. And so as that list grows on clinicaltrials.gov, you'll see some familiar faces with partners that we have had for a long time. But I'll also say that we've expanded our reach into some academic centers that have not opened up studies before. So we are actually pretty excited about the breadth and the variation in the types of sites, both old and new, community and academic, as we're getting this study up and running.
spk11: Thank you. Please stand by for our next question. Our next question comes from the line of Tyler Van Buren with TD Cohen. Your line is open.
spk12: Hey, guys. Good evening. Congratulations on all the progress. So if enrollment for Alpha 3 is expected to complete during the first half of 2026, can you elaborate on what the interim EFS analysis during the first half of 2026 is expected to look like and what its specific purpose is and why you need it just ahead of the final EFS analysis by year end?
spk04: Hey, Tyler, Zach. Thanks for the question. As we mentioned, we've modeled out and we've discussed in this venue before, we've modeled out what the expected time to event is, EFS in this case, for patients who are in the observation arm, and it's quite short. I mean, the prognosis of these patients with MRD-positive disease at the end of our CHOP is poor, and the time to progression is measured in weeks to months. So that's given us the opportunity to perform this interim analysis, and we haven't gone into details around what the volume or the percentage of the data that we will be examining at that interim analysis is, but it will allow us to potentially initiate conversations with FDA. It will also allow us to get a sense of what the potential market penetration could be So there are a lot of significant practical benefits to having an early formal look at that data that will certainly guide us in the direction of what we expect for the primary as well. So all those balls will be able to begin rolling in the first half of 2026. That's our vision.
spk11: Thank you. Please stand by for our next question. Our next question comes from the line of Jack Allen with Bayer. Your line is open.
spk19: Great. Thanks so much for taking the questions, and congratulations on the progress made over the quarter. I just wanted to ask a couple here. The first, which is on the manufacturing process update, it sounds like all the product is now coming from CellForge One. I just wanted to ask if you have any sense for any differences in potency as it relates to CellForge One manufactured products as compared to CMO products. Were there any changes in the process there, or is it still the alloy process that you're utilizing at both centers? And then, Really briefly on CLL, I was hoping you could provide some context as to what we should look for in early 25. We'd love to hear about the size and breadth of that data set that we should expect in early next year.
spk16: Hi, Jack. Thanks for the questions. Let me take the manufacturing questions, and I will defer the CLL question to Zach. In terms of manufacturing, we have successfully manufactured all the products that we are currently investigating in the clinics at CF1. With respect to the details of how we are characterizing, we have a very high standard of characterizing the products that includes the potency. The way that we characterize the potency is looking at both what's required for the release of the product as well as other characterization that we use for the internal learning and for the improvement as we work on the processes. You know, it can really go too much into that, but so far, the products that we are manufacturing at CF1 is meeting all the standards to take it into the clinics.
spk04: And Jack, I can address your question on CLL. So, you know, we are obviously pouring most of our efforts and attention into the Alpha-3 program, and And CLL continues to run alongside. And so as we look towards that data update in early 2025, again, I would say you set the expectations roughly around the same target number of patients with as much follow-up as we can generate.
spk11: Thank you. Please stand by for our next question. Our next question comes from . Your line is open.
spk13: Hey, guys. Good evening, and thanks for taking my questions, and congrats again as well on the progress. On allo329, the potential to reduce or eliminate lymphodepletion is obviously very attractive, but it might be also important to distinguish between those two words. So I'm curious to know how many patients do you think you'll need to treat with 329 to actually figure that out, and do you think we might have an answer to that in 2025 on your first readout on this study?
spk16: Let's take a, this is David. Let me take on that question. You know, what you are asking is a very important question, but I think it's too early to sort of, you know, lay out, you know, what, how we are thinking about the lymphodepletion. It is, it will be, you know, one of the primary focus about phase one, you know, exploring the different lymphodepletion, as well as looking at ways to reduce the, you know, the the lymphodepletion that's currently being used in the Othala CD19 CAR T trials in autoimmune. But what we know from the 3 to 9, you know, with a dual CD19, CD70 approach, we do have many different options that are available in the study design to test, you know, this important question.
spk11: Thank you. Please stand by for our next question. Our next question comes from the line of Sammy Corwin with William Blair. Your line is open. Hi, thank you for taking our question.
spk07: This is Brooke Schuster on for Sammy. So regarding the community centers, given that these centers are less likely to be like less experienced or have no CAR T experience, are they getting extra training to be prepared for CAR T treatment, such as recognizing safety signals and ensuring proper MRD testing, et cetera?
spk04: Hey, Brooke, this is Zach. Thank you for the question. So we approach every site kind of with the same view in mind, and that is, you know, we want to make sure that they have all the tools and the information they need to safely manage their patients. So for the large academic centers that have been doing CAR for 10 plus years, they would need potentially a little bit less training, although we still do offer that training, than somebody who has somewhat less experience or maybe even no experience at all. We feel like we're in a pretty good place starting out because our safety profile for semacell, as we've shown in our Phase I study, is actually fairly well tolerated with very little, in fact, no high-grade CRS or ICANNs. sort of an infection profile that is very consistent with patients who are receiving treatment for various different types of cancer. So, you know, from the perspective of training specific to management of CAR T side effects, you know, we're starting off with a leg up already. I will also add that many, if not all, of these community centers are familiar with CRS and ICANS and other T-cell mediated adverse events because they've been giving bispecific therapy for LBCL and other cancers now for months or even years if they were open for trials. So these are not truly naive centers. They stock Tocilizumab in their pharmacies, et cetera. So we actually feel like this should be fairly manageable, but it's a good question, and we are making sure that each center is is fully trained to handle this safely. You also asked about collection of the MRD test. I'm proud to say that this is actually a fairly straightforward test that these sites will have to collect. In fact, it's very similar in terms of what they have to do on their side to just about any other test that is collected now for lung cancer or breast cancer. There's a piece of tumor that is sent in and then a blood test, and then Foresight handles the rest. That should hopefully have very few errors or any difficulties.
spk11: Thank you. Please stand by for our next question. Our next question comes from the line of Matthew Beigler with Oppenheimer. Your line is open.
spk01: Hey, guys. Thanks for the question. It's great to be back. Wanted your opinion on the importance of T cells in contributing to certain autoimmune diseases. It seems, you know, obviously like an industry where singularly focus on the B cell reset. But I guess, you know, with some of the data mentioned that you are on relapses, I'm just curious, you know, it seems like your dagger technology not only can maybe do away with lymphoconditioning, but also target reactive T cells. So just kind of curious, like, if you think you might have an edge on other players in the autoimmune space. Thanks.
spk16: Hey Matthew, great to have you back. A very important question as we think about CAR Ts in autoimmune space. I think we have to start in the design of the product, thinking about the disease from the fundamental biologic perspective. Autoimmune disease is never a disease of B cells. It's always B cells and contributing T cells that really eventually manifest the symptoms of autoimmune diseases. So from that perspective, we felt being able to target activated T cells, and we achieved that by going after CD70, which I expressed on the activated T cells. We believe that this is very important to maximize the potential of allo329 across different autoimmune indications. So yes, we have to show it in the clinical data, but it definitely increases the potential of allo329 versus CAR T programs that are simply targeting B cells.
spk11: Thank you. Please stand by for our next question. Our next question comes from the line of John Newman with Canaccord. Your line is open.
spk03: Hi, guys. Congrats on the progress, and thanks for taking my question. So, David, we've seen some data recently from two autologous CAR T programs in the autoimmune setting, which I'm sure everybody on the call is very familiar with. My question is, is there something different beyond the targeting of active T cells for IL-329, for example, manufacturing or another aspect that you think could result in more consistent results when you run the study. I think we're all trying to figure out exactly what the autologous data mean, but what I'm curious about is, is there something specific perhaps in the manufacturing process or somewhere else for 329 that could give more consistent results in the future? Thanks.
spk16: Hi, John. Thanks for that excellent question. I mean, you know, the manufacturing at the end, you know, is, you know, one of the, you know, big differences, you know, that can result in a difference in the outcome. We don't have all the details of, you know, how different programs that have taken CD19 CAR T into the autoimmune space, you know, have been manufactured. But definitely, you know, we do strongly believe that how the cells are prepared, whether the cells are frozen before administration or administered without freezing, all these things together with the way that the cells are expanded makes a big difference. Unfortunately, the details are somewhat lacking because the information are somewhat kept as a proprietary information, but I think that is a very important question. As for the 329, we have taken a different approach of manufacturing. Fundamentally, how we introduced transgene that express CAR, whether we do lentivirus, we have, in this case, taken the path of doing site-specific integration. using CRISPR-based nuclease and AAB. And, you know, studies have shown that kind of approach can potentially improve the consistency of the final product, which we believe is very important as we think about indications such as autoimmune. So stay tuned.
spk11: Thank you. Please stand by for our next question. Our next question comes from the line of Ben Burnett with Stifel. Your line is open.
spk02: Hey, thank you very much. I also wanted to ask about allo329 and autoimmune disease. There was a recent disclosure with a CD19 allogeneic CAR T from BRL Medicine. This was via an academic study in China, but we thought the data looked quite good. That BRL asset, though, contained a number of edits and modifications. So, I guess the question is, number one, it'd be great to get kind of your thoughts on those data. And just secondly, I guess, how does the technology that you're implementing with Allo329, with Dagger, and everything else sort of compare to that BRL asset?
spk04: And this is Zach. Thanks. Very insightful question, and thanks for bringing up that exciting report. So we share, I think, the enthusiasm of around that first report of responses to a CD19 allogeneic CAR T in three patients with two different autoimmune indications. We feel that that is a very strong proof of concept that this platform, which we have demonstrated is functional in oncology, is likely to also be operable in autoimmune disorders. You rightly highlight some of the strategies that they have employed to ensure adequate expansion and persistence. They have taken what might be called a sort of a cloaking strategy where they've eliminated MHC molecules and they've also disrupted the PD-1 axis. This is a strategy that has been tried by others and I think it's probably still too early to say whether that is globally speaking a successful path. Our plan, it has relied on the dagger technology to ensure that we do get that adequate expansion and persistence and we feel very comfortable that this sort of dagger versus the cloaking strategy will deliver benefits and we've seen this now in the RCC program with the Allo 316 product, where we get up to two logs, better expansion, and improved persistence, even with a de-intensified lymphodepletion regimen. So I think every allogeneic platform is going to have to deal with the idea of premature rejection, and we are very confident that the DAGRA is going to give us a path forward there.
spk11: Thank you. Please stand by for our next question. Our next question comes from the line of Luca Issy with RBC Capital. Your line is open.
spk15: Well, great. Thanks so much for taking my question. Congrats on the progress. Maybe just a quick one, David or Zach. What's the latest thinking of whether you think that anti-CD52 is actually needed as part of lymph depletion in alpha-3? I was always under the impression that adding CD52 was actually important to discriminate between endogenous and exogenous T-cells, but it feels to me that you're maybe downplaying that a little bit recently, and maybe you're now thinking that anti-CD52 may not be needed as part of the depletion. Juan, am I right? And if so, how should we think about the overall profile of your drug in a scenario where anti-CD52 is needed versus not needed? Any thoughts there? Much appreciated. Thank you.
spk16: Yeah, Luca, let me take on that question. You know, we do believe anti-CD52 antibody is very important to create the persistence as we have demonstrated in the relapsed refractory in a large B-cell lymphoma setting. When it comes to the Alpha-3 study where we are treating minimum residual disease, we are talking about a different clinical setting. These patients have minimal disease, which we do not believe may require which may not require, you know, the kind of persistence that is needed to treat large volume disease. That's why, you know, we feel that, you know, testing the lymphodepletion both with and without the CD52 antibody or allo647 that we are using is an important scientific question. And also, you know, by doing the study as we have designed alpha-3, it gives us really an opportunity to carefully review and dissect the contribution of 647 as a lymphodepletion in the MRD setting. So that's a question that is to be tested. And in either case, in the Alpha-3 study, we are counting on the outcome as measured by the EFS. And whether we proceed with FC or FCA doesn't really change in what we are trying to do with the Alpha-3 study.
spk11: Thank you. Will you stand by for our next question? Our next question comes from the line of Tony Butler with Rotman and Renshaw. Your line is open.
spk18: Hi, this is Josh for Tony. David and Zach, you mentioned briefly touched upon this, the MRD testing for patients, and I'm assuming that this is done very soon after the patient is done with the sixth cycle of chemotherapy. Now, I wonder if you could flesh this out a little bit, for example, given that sometimes disease comes back rather quickly for MRD-positive patients, how long it takes for patients to get the results, and additionally, whether the test is something easy or does the patient need to go to a specialized facility to be tested? Thank you.
spk04: Hi there, this is Zach. So you're absolutely spot on. This is a race against time to make sure that we can get the dose of semicell in while the patients are still in remission. And in fact, we think that that speed is actually what makes an aloe CAR T product best suited for this type of a trial. As to the specifics, so first, The patients will get their MRD tests at the centers where the study will be open. So there's no need to go to a specialized place to get the blood drawn. All of that will be collected just as any other clinical trial biospecimen is collected every day in other trials. And that has been sent in to Foresight who runs the test. That test is, we will have that result back within one to two weeks, hopefully closer to one week in most of these patients, but very, very quickly. The test itself is drawn more or less when the patients come in and get their first follow-up scan after their sixth cycle of RCHOP. So this is a standard of care scan taken between three and, say, six weeks or so after that last dose of chemo. If the patient's in remission, that makes them potentially eligible for Alpha-3. They have their MRD test drawn. They get the result back in a week to two weeks. And if they're MRD positive, that patient would then potentially be eligible to come into the trial. So it all happens very, very quickly. And the likelihood of a patient relapsing in that interval is non-zero, but it's actually quite low. because most of those relapses do occur, say, you know, at the time of the next scan, which may be two to three months later. So we're hoping to get all this work done while the patients are still in remission so we can effectively deliver the consolidation dose of semicell.
spk11: Thank you. Please stand by for our next question. Our next question comes from the line of Rennie Benigerman with Citizens JMP. Your line is open.
spk17: Hey, good afternoon, guys. Thanks for taking the question and congrats on all the progress. Just regarding Allo329, could you give us a sense as to when we might see some preclinical data and what we should be kind of focusing on? Because, you know, correct me if I'm wrong, persistence doesn't seem to be, you know, kind of the more important factors to focus on as compared to, you know, depth of depletion. But, you know, any feedback would be great on that. And I guess just as a follow-up, Just given there's some work with PCMA targeting agents in autoimmune as well, is there a chance that allo715 might see a revival? Thanks.
spk04: Hey, Rene. This is Zach here. So, the first question on the preclinical data, we are hoping to share that soon, and There are related data from a somewhat related product that we shared last year at CITSE, so for those of you who can't wait for the update with the 329 product, you can get a little bit of a preview from the data we shared last year. That is using the old gene editing platform, so we've made a few updates, but that will be a good appetizer for you as we are preparing that preclinical data for later this year. As far as the question around persistence, you know, obviously that's very hard to measure outside of a clinical trial, but I would agree with the premise of the question that, you know, our belief, which is built on the data that's been shared from the autologous field, as well as that paper that was alluded to previously in the Allocarti, is that it's likely that the persistence is going to have to be shorter here or could be shorter than it does need to be in oncology, which we think bodes well for allogeneic products like Allo329. Finally, your question around BCMA and 715. We currently do not have any plans to put 715 into the clinic for treatment of autoimmune disease, but of course we'll be watching that field very carefully in the coming months and years.
spk11: Thank you. Please stand by for our next question. Our next question comes from the line of Byron Amin with Piper Sandler. Your line is open.
spk14: Yeah. Hi, guys. Thanks for taking my questions. Maybe to start on the CLL program, I noticed a slight push out on data from year end this year to early next year. Are we still, I guess, expecting 12 patients' worth of data? And should the comp be, you know, the Beyonce 20% CRA? Is that, I guess, what we should be looking towards when we receive the data? Yeah.
spk16: Hi, Bjorn. Let me take on the first question with your eagle eyes. I guess you noticed that we have pushed out the timeline a little bit. That really comes from the fact that in the current environment, we have the need to prioritize and focus on the Alpha-3 study. That is our primary interest in rolling into the study and monitoring how that study advances. So it's really a reflection of reallocation of internal resource to you know, support the Alpha-3 study, you know, which so far is, you know, progressing extremely well. And, you know, and for that reason, you know, we do not want to burden the team by, you know, asking, you know, them to also accelerate the CLL study. You know, our target for the phase one study, you know, in the CLL has not changed. It's essentially targeting approximately 12 patients enrollment. And the bar that we are aiming for is, as we have previously communicated, is set by what we have seen, you know, with the Brianzi in the relapsed refractory CLL patients.
spk11: Thank you. Please stand by for our next question. Our next question comes from the line of William Pickering with Bernstein. Your line is open.
spk06: Hi. Good afternoon. Thank you for taking my question. Congrats on all the progress, especially the activation of the community sites in Alpha 3. What are some of the attributes of community sites that seem to be making them more or less interested in participating in the study? Is it about infrastructure, prior clinician experience with CAR T, or some other factor? I'm just trying to get a sense for how to subsegment this community setting, given that it represents such a large percentage of patients. Thank you.
spk04: Hey, William. This is Zach. So, excellent question, and, you know, let's sort of help you parse that out. So, I think, first and foremost, the signal that we're hearing loudest and clearest from our community partners is that they are really excited to be able to offer CAR T to their patient population. As I said, most of these community centers don't currently do that. They have to refer their patients out when they relapse. As I mentioned before, you have to have a clinical relapse in order to be eligible for all approved CAR T. If those community centers do not offer CAR T, that means that those patients have to be referred out. Oftentimes, those patients don't want to be referred. They will accept a non-CAR T option for salvage therapy if that allows them to stay with the doctor that they've come to trust and in the center that is close to their home. As to why these community centers have not begun to offer autologous programs, the reasons there are varied, but to one degree or another, they all come down to the investment that would be required by these centers to build out the infrastructure in terms of specialized team members, apheresis capacity, and potentially even inpatient management facilities to actually offer these products safely to patients. So we really believe that we have threaded this needle here and are offering an off-the-shelf option to patients who are in need. and who likely could derive a significant benefit while all being able to be done at the centers where they are most comfortable and they get to stick with their doctor.
spk11: Thank you. Ladies and gentlemen, I'm sure no further questions in the queue. I would now like to turn the call back over to management for closing remarks.
spk16: Yeah, I'd like to thank you all of you on the call for your interest and continued support as we progress on our industry-leading programs. last quarter and going forward, it will be all about the momentum. You know, we are more energized than ever with the path forward and the building momentum that we believe will lead to sustained growth. So, operator, thank you, and you may now disconnect.
spk11: Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.
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