Hey, welcome everyone. Welcome to the Piper Sandler healthcare conference. My name is Biren Amin, Managing Director here at Piper Sandler. I'd like to introduce our next company, Cargo Therapeutics. We have Gina Chapman, their President and CEO. Welcome, Gina. So I guess, you know, tell us a little bit about Cargo Therapeutics, your CAR-T cell therapy developing CD22 CAR-T. Maybe tell us a little bit about that program. Sure. Okay, so I'll start with Cargo Therapeutics. We're a clinical-stage biotech. Our mission really is to design, develop, and deliver next-generation, potentially best-in-class and curative cell therapies for patients with cancer. We do have an initial program, FIRCE-1, which is a study, a potentially pivotal study, phase II study of firi-cel in large B-cell lymphoma, specifically for the first indication in patients who are relapsed refractory to CD19 CARs. I think importantly, CD19 CARs have been absolutely transformational for patients, potentially curative for about 30%-40% of patients who get a complete durable response. And so that's incredible. But there's about 60%-70% of patients who do not. And the circumstances there are pretty dire. And we'll probably get into that. And we're looking to help those patients initially with our first program and indication. So firi-cel, you've already generated phase I data. Maybe talk a little bit about that in terms of, you know, what you saw and what gave you the confidence to move that into phase II because of that phase I data. Yeah, so Stanford generated the phase I data with FIRCE-1 just to clarify that, and I think that's important. The phase I data that Stanford generated was absolutely compelling for this patient population I already described as, you know, having failed a CD19 CAR, and for those patients, the median overall survival at that point in time is only six months, so it's just a very, very high unmet need population, heavily pretreated, very advanced disease and dire outcomes, obviously, so they were able to generate in. I'll talk about dose level 1, which is the dose level we're bringing forward in this potentially pivotal phase II study that we're running, generate a 52% complete response rate, and so that is phenomenal. Again, that's in line with what you see with CD19 CARs in an earlier line of therapy with such a difficult to treat patient population. So that's very compelling. I think that's one reason why we were able to get so much interest in this phase II study, obviously, and in the company and we can talk about execution. But that interest along with our execution, we're already just over a year now dosing patients at 57 patients dosed and looking forward to interim results in the first half of next year around the corner. And so the phase I highly refractory patients. Yeah. What's the typical, you know, treatment option for these types of patients if they were not on the phase I trial? Yeah, there's no standard of care for patients who have been relapsed or refractory to CD19 CARs. There are treatments you can give, but there's, again, nothing that's potentially curative that's been available. And so at that stage of time at the phase I, again, the median overall survival is six months. Now, since that phase I was conducted, bispecific T-cell engagers have been approved through accelerated approval. Epcoritamab and glofitamab are both available now. They were primarily studied in relapsed refractory large B-cell lymphoma, which includes CAR-naïve. But there was a subset of patients who were CAR-experienced. And so there is something that patients, that physicians can give. It's generally believed and based on the data that the most, I'd say, likely response that's durable over time is with an autologous CAR T-cell therapy. There's still a question about whether or not these will be standard of care. I think we'll see as time goes by what their long-term durability looks like. But in this heavily pretreated population where you fail the CD19 CAR and there's a subset of patients, the glofitamab data is usually the one that I quote, but they're about the same. You're seeing about a 20% durable response out over time with the bispecific T-cell engagers. We'll just have to watch that and see if that durability holds. But at 20%, generally most KOLs are thinking that it's preferable to give another CAR based on the Stanford data and get a higher potential cure rate. And so Stanford data, 52% complete response. How does that translate in terms of the duration of response or median PFS that they've seen? Yeah, so at a year, 75% of those complete responses were still durable, which is really fantastic. We do have coming up at ASH an abstract that Stanford's presenting that gives three-year follow-up now. This is a data cut according to the abstract that's been published so far of July. Sometimes Matt Frank brings a more recent data cut when he actually presents. But what's published so far in the abstract is July and the July cutoff. And with 36.7 months of follow-up, what he published was a sort of a duration of response and an OS. The OS is about 47%, which is phenomenal. The duration of response was 23.2 months, but that's for all patients. For the patients who achieve the complete response rate, that has not been reached. That's pretty. It looks to us as if we're continuing to see this durability out for firi-cel now for three years. I mean, that's pretty phenomenal for a late-line patient to be able to go out three years and beyond in those that have achieved a complete response. Right. So a higher CR rate than what we're seeing with now, what might be a new alternative therapy for this patient population, but higher CR and really, really strong durability is what we want to see. And that's what Stanford's seeing. Now you're running a phase II pivotal study called FIRCE-1. Right. And you had mentioned that you've enrolled 57 patients to date. What are plans in terms of data disclosure? When is the study finishing enrollment? Okay, so we call it a potentially pivotal phase II. We need to generate results and discuss that with FDA and a path forward. But they did indicate to us that it'd be reasonable to expect a potential approval pending results. So that's why we call it potentially pivotal. But we did design it as a pivotal for that reason. We believe it has that potential to be that. And let's see, one other thing that you, sorry, that you asked me. In terms of completion of the trial, when would we expect that and data? Yeah. Okay, so 57 patients dosed, not enrolled. That's what I wanted to clarify a couple of things. So we have 57 patients dosed, and that's as of November 8th. And so we keep making progress. There's a lot of enthusiasm, and we're seeing great momentum. Every single month we're seeing more patients dosed than the month before. All 31 sites activated and have been now since the summer. And so just great momentum there. We are on track now for interim analysis, as we've been saying, in the first half of 2025. So right around the corner. And so you have three cohorts within the FIRCE-1 study. The primary one is cohort one. But then you also have cohort two and cohort three. Tell us a little bit about those cohorts. Okay. So the primary cohort one is sort of the primary cohort, and that's CD19 relapsed refractory patients designed like the Stanford study. Cohort three, I'll go to next, that is designed because we've seen this evolution with the bispecific T-cell engagers now having accelerated approval since the first line or the phase I study was done. So we've added that cohort and that CD19 relapsed refractory and bispecific T-cell engager relapsed refractory, very, very advanced, heavily pretreated population. The intention is to have 81 patients in cohort one and about 20 patients in cohort three. What's novel is cohort two. So that's novel as well. That hasn't been done before, that heavily pretreated population. Cohort two is also novel, and that's taking a best practice, kind of a learning and making a best practice from the CD19 pivotal studies. They did not actually study in a controlled way during their pivotal studies doses that basically were out of spec. And so if you have out of spec doses that look like they could still be viable in terms of delivering a product that might work to patients and be safe and the patient's consent, the investigator consents, we consent that that product can be given. We have the opportunity to capture that data on that out of spec product and potentially over time with enough data and enough out of spec product to be able to expand our specs in a future label. We've had such strong manufacturing success. We only have two patients in that cohort. So 57 dosed, overall 47 in cohort one, eight in cohort three, and only two in cohort two. So again, really strong manufacturing success. Very low fail rate from a manufacturing standpoint, which is great. We know other cell therapy companies have had issues in the past on manufacturing to spec. I guess, you know, this was manufacturing that was done in-house. Or can you tell us a little bit about the CMC effort that you put in place? Yeah, we have deep experts in-house for process development. We do transfer that process to CDMOs. We have pursued a CDMO strategy. We have two CDMOs providing the product for the clinical studies. And this is a process that is ready for commercialization. That's also part of our strategy. So we can go quickly to commercialization based on pivotal. And so to be able to see this kind of manufacturing success at this stage of development is really quite phenomenal. And I want to say this has the benefit also of delivering that reliable and predictable supply now before commercialization, which will help us during commercialization to have that confidence. It's one of the reasons why you see the momentum in dosing, because investigators can see that their patients will very likely get a product and they'll be able to deliver on that hope that they're trying to give them. And so I think one of the reasons why Cargo, I believe, stands out right now in this particular setting for patients, and we're able to say that we're on track to share data next year after right now just a little over a year of dosing patients, is because of not only the phenomenal, really compelling phase I results, but also because we've been able to execute and deliver something that's predictable and reliable. That does matter. Process really is the product in cell therapy, and you have to be able to deliver that, and you have to be able to give that confidence that the product's going to be there to go through the apheresis and the waiting time that is required by patients with such advanced disease. I really am emphasizing that a lot because what we're seeing in our competitive landscape is that we've been out ahead of others, but our lead is growing because we're just not seeing the dosing or the data coming out from others who are in phase Is right now. That's fair. Right? That's fair. Yeah. And so, I mean, clearly manufacturing is important. I mean, we've heard that as well. You know, where physicians want that confidence to be able to get that product back for their patients. It's not easy to do. This is where, like, I talk a lot about the expertise we have at Cargo. We have cell engineering design expertise, which we can talk about if we move to CRG-023. Of course. We also have expertise in executing on clinical development, which is clear, as well as this manufacturing piece, which is so, so important for cell therapy. I guess one last topic around FIRCE-1 is what does the safety profile look like with firi-cel? Yeah, it's important. Sometimes I don't emphasize that enough, but the safety profile coming out of Stanford is really strong. And so I'd say, you know, a lot of the benchmarking is to the CD19 CARs, right, that are used in the earlier line of therapy. Our CR rate, CRS rates in terms of grade three CRS were very, very low to zero. And same with ICANS. And the CRS rate, grade three, matters, but I don't tend to emphasize it that much because the management of CRS has gotten so much better. So there has been a shift from when, say, Yescarta or Breyanzi, Kymriah did their studies. So I don't talk about that very often, but CRS looks really good. In terms of ICANS, though, I do speak about this a lot, and there's a real advantage here for firi-cel, which is one reason we're looking to hopefully go into earlier lines of therapy. And that is the immune effector cell-associated neurotoxicity syndrome, ICANS. That is 0%, and this is really important, 0% grade three. These patients, when they get ICANS, they are encephalopathic. They're very confused. They go into the ICU. That's about $60,000 per patient, but it's a burden to the healthcare system, to the patients, to their families, their caregivers. And so avoiding that is a huge potential advantage. That's gotten the attention of investigators as well. And so the tolerability safety profile looks really good. Happy to answer any other questions about that, but we're obviously studying that and tracking that in our own study. We did move past an initial safety review with IDMC back in the spring, a second one in the third quarter, which was both safety and futility. Passed that with no modification. So we're quite optimistic as we head into interim analysis again in the first half of 2025. So interim analysis, first half of 2025, what can we expect on that? Is it going to be top line press release from the company saying, "Okay, we've stopped the trial based on certain thresholds that we've met"? Is that something that we should be expecting, I guess, on the interim? Interesting question. I mean, I think whatever we issue will be dependent on the results, right? And so the strength of the results before we would issue anything, we have to review that with FDA, at least along the lines you're talking about. Our planning case is that as we designed with FDA, we need to dose 100 patients and have adequate follow-up generally in cell therapy. That's six months to see CRs and see what your durability is on those CRs of a decent level for at least six months. So I think what you're talking about would be, you know, a best case is this is a high unmet need population, but that's not our planning case. But we'll have to wait and see and see what the results. One of the reasons to pull an interim analysis is to acknowledge this is a very high unmet need population. And so, depending on the strength of the results, there could be different opportunities. That makes sense. I guess, you know, so exciting 2025 with first half interim analysis. You talked a lot about, you know, the safety profile being 0% ICANS. You know, CRS rate is also very tolerable. You know, there's a lot of discussion about outpatient therapy with CARs. Is that a potential with firi-cel? Yeah, it is a potential. We'd have to look at that as like an add-on kind of cohort or some sort of something to do, you know, if we potentially go into earlier lines to add that in. So, but definitely, definitely something we should be looking at and we've talked about. Currently, what I think we're most sort of prioritizing most is another study that we would start in pediatric B-ALL. There's great data out of NCI and Stanford in pediatric B-ALL. So starting that study as well as looking at how we get into earlier lines and what we might be able to do there. We've been in discussions with FDA about that. We're waiting for interim results to be able to also figure out what that path forward is. And. Outpatient is definitely a part of that. Pediatric B-ALL, would that be a refractory patient population? That's what's been studied in the phase Is, yeah. Okay, that's great. I mean, high unmet need there as well. Very high unmet need. A lot of interest, great data. We did prioritize at Cargo getting into this CD19 relapsed refractory setting a lot higher. I'd say patient demand and unmet need size of population as well as unmet need. There was really nothing there at the time, so yeah, both are important, but we decided to prioritize this and look forward to starting a pediatric B-ALL study as well. And then ASH, there's also phase I data from Stanford in mantle cell lymphoma and follicular lymphoma. Some pretty encouraging response rates and CR rates, at least in the poster. Tell us a little bit about that in terms of, you know, what your efforts in those two indications would look like. Absolutely, so Stanford, essentially what Stanford has done is a phase I-B study, and they've dosed six patients so far with MCL and follicular lymphoma. They're adding other types of lymphoma as they continue to recruit patients into this. The first four patients consecutively dosed with MCL and follicular lymphoma, all 100% of them achieved a response, so it does look encouraging. It's early, small sample, need follow-up, but we're definitely keeping an eye on that, and of course, when we think about lifecycle management for firi-cel while we're prioritizing B-ALL in earlier lines, this could also potentially be considered. Great. And so you've got a lot going on with firi-cel in the refractory setting. You talked a little bit about, you know, potentially evaluating early lines. When do we start to hear more about those efforts? Yeah, I think I mentioned we'll need to have those results from this study interim analysis before we could have that next conversation with FDA to determine the path forward there. But we're very, you know, excited about the potential for firi-cel in earlier lines because generally, for example, with the CD19 CARs, what you see is even better efficacy earlier. And given our safety profile that I outlined and that potential benefit to avoid ICANS that you see with CD19s and the potential for even stronger efficacy and durability, moving to earlier lines is an obvious sort of benefit for patients. And so it's also a larger patient population. So definitely in our interest to do that. And we've been working and discussing that with FDA and just really need to see the interim results so that we can determine that path forward. Great. So, exciting year for firi-cel next year. But also, I think at ASH, you have a second program, CRG-023, with a poster that's going to be presented at the meeting in a few days. Tell us a little bit about 023, what the objective is there? Okay. So I'm very excited to be here. I'm also excited, Biren, and thank you for having me to go to ASH from here and get to San Diego for this event. This is our first poster presentation from Cargo. And what that means is this is our sort of first designed, engineered program as well in CRG-023. So we're really proud of it. Basically, CRG-023, I think really, I hope highlights for those of you who are watching closely that design matters and Cargo knows that design matters when it comes to cell therapy. So when you see what the intentional design of this product is, I think that stands out. But even more importantly than design is, okay, does that design deliver? And then we've got preclinical data in vitro and in vivo that shows that this really does have the potential to deliver a best-in-class, potentially curative therapy for more patients across a broader range of B-cell malignancies. And that's because getting to design, what we've done is a binder campaign to optimize the binders of CD19 and CD20. We tried CD22 as well and we're using our own binder there. We didn't find a better binder, but for CD19 and CD20, we did. And we were able to really optimize those new human binders compared to benchmarks that are already out there that most companies tend to use over and over again. So we took the time, and this has been two and a half years of work. We took the time to identify and optimize these binders, went through thousands of different binders and then iterations of binders. Then we optimized the ordering of those binders and engineered these onto one single vector. So these are, it's a tricistronic. So each of the CARs independently expresses. And what we're seeing in the data is that with continued challenge of the tumor, this product continues to sustain anti-tumor activity. So we keep challenging it. It keeps coming back down in terms of tumor compared to benchmarks where that doesn't occur. And so that's exciting to see. We're also seeing this activity in very, very low doses. And then there's, you know, the data will be in the poster and look forward to talking about that more once it's presented. Tricistronic design. Tricistronic. From a translational standpoint, if, for example, a patient doesn't have CD20 expression or CD19 expression, the CAR would still be active and would be effective in that type of a patient. Yeah, and we've got the preclinical, again, it's in vitro and in vivo data to show that regardless of which antigens expressing, you're seeing the activity and we're doing that with continued tumor challenge. So that work will be shared during the poster presentation. That's great. And then what are plans in terms of timelines to move this into a phase I study? What we've communicated is that we expect an IND in the first quarter and we're making great progress on that. And so can't wait to share that news. And then we expect first patient dosed in 2025. And I'll narrow that once we have the IND because then we'll have good ideas as to when. But we already have sites interested and so we're already executing on this plan. That's great. And would the patient population be a refractory large B-cell patient population or would you go into like an earlier line setting? I'll share more when we have the IND accepted. I think that's important. We had a very positive pre-IND meeting, which I have shared publicly, that was in the third quarter with FDA. What we've said so far is it'll be an NHL. This is an interesting nuance. So since Stanford ran the phase I study for firi-cel, we have the IP from NCI. We achieved analytical comparability with what Stanford studied with firi-cel. We need to achieve clinical comparability. That's why interim analysis, that's why we're doing an interim analysis on a potentially pivotal study so that we can pave that path forward more quickly. With CRG-023, this is our product. We're conducting the phase I. So we can do this in a way that I think strategically allows us to get more quickly to a broader set of patients and then be able to design a pivotal that also can achieve that. So we've said so far NHL, but we're trying to do this in a way that helps us benefit as many patients as quickly as possible. So clearly exciting developments for next year on that program as well. Yeah, but just a slightly different, hopefully, path forward than what we're seeing with firi-cel because we're conducting the phase I. Got it. Got it. And I guess from a CMC standpoint, similar type of process. What's the difficulty in terms of moving from firi-cel to a CRG-023? So the opportunity rather than the difficulty is take all the learnings we've had as well as progress in the field and integrate that into CRG-023. We tend to, we have a very strong tech ops team and, you know, Shishir Gadam well, and he's an absolute expert in this field. He's at Juno, Celgene, right? I mean, and BMS for that, Merck, Genentech. This is a true expert in the field and a great leader. So what he's done with firi-cel, just expect that he's continuing to be a very strategic, very well-informed sort of leader who is looking at the opportunities to, you know, create an at-scale, rapid sort of manufacturing process to deliver as much benefit to as many patients as possible with the lowest cost possible. So he continues to iterate sort of that strategy for CMC and build those new best practices into CRG-023. So we look forward to sharing more as we, you know, once we have an IND and can, yeah, connect the two of you again. Awesome. So synergies clearly, you know, from your firi-cel experience into CRG-023, which is great. And I guess, you know, as we think about firi-cel data next year, potentially pivotal, you know, data set. And I know you're going to talk to FDA, but let's assume best case scenario, you get the green light. We're seeing encouraging complete responses, durable responses, and you're able to, you know, file a BLA at some point next year on the data set. What does commercialization look like in those efforts? Talk about, you know, what your thoughts are around that. Okay, so we're building a company and have already kind of built sort of the expertise that we need to be fully integrated from design through development to delivery. And delivery is not just like tech ops delivering the product, but also commercializing. We already have a very; it's a very lean, small commercial team, but of deep experts in cell therapy at the company thinking about things like ensuring that access is available, forging those relationships, but also that the, basically that the mechanism to sort of follow the cells from clinical study is seamless into commercialization. That's part of actually your BLA is to have that sort of process engineered and designed. So we've already been making those investments, which I think is also important. So we're absolutely already paving the path to commercialization. One of the things we have is our plans ready to go upon understanding our path to BLA so that we can really build the larger team that we'll need, but it's still a pretty lean effort to go after CD19 relapsed refractory. It's one of the reasons why this is such a great beachhead for a biotech like ours. It's actually doable, and we have, my background, I think you know, is mostly a commercial background, commercial and operations, and so, yeah, we have the expertise we need at the company, and I'm just honestly really excited to move into that phase of growing the company. I think importantly, understanding that path to BLA with FDA is the. It's the gate that we're using before we make any further investments, so I'm also very careful with the capital that we've been entrusted with from our investors. And I do try to maintain sort of a lean team and have the plans in place so that we can take off quickly. And having experts around the table really does enable us to do that in that way. So it's gated right now. Great. So thank you for coming to Piper Sandler and, you know, some exciting, I guess, data at ASH in a few days and then I guess more developments in 2025. So looking forward to those. Thanks, Gina. Yeah, Biren, thanks again for the invitation to be here. It's been a pleasure talking to you. Great. Okay, thanks. Thank you.