for joining us on this next fireside chat. I have the pleasure of having the CEO of Cargo Therapeutics up here with us, Gina Chapman. Gina and the Cargo team have been executing very well since the IPO fall of 2023, particularly during a difficult time of the markets as well. And you guys have been executing and enrolling and working on your potentially pivotal study. Maybe we could just start off, Gina could give us a brief introduction about the lead program at Cargo and what it's addressing and the pivotal study that you're enrolling, and that would be a great setup to go into some of the details. All right. Well, hi, everyone, and Mike, thank you so much- Yeah ... for this invitation to be here with you, and your team. So Cargo's a clinical stage company, and as Mike said, we do have a program that's potentially pivotal phase II. But there's more to Cargo than that, so I will just say that we do have aspirations to be a leading cell therapy company, and I do think we have the technology, the people, the know-how to achieve that. Our lead program is a great beachhead sort of for us to show what we can do to launch into the market, bring a potentially curative therapy to patients with cancer. We'll talk about that in a minute. As well as develop and what we believe could be best-in-class CAR T-cell therapies to bring even more cures to more patients. And so that's what we aim to do, and we've got the team with the expertise in oncology and cell therapy to do that, and yes, they've been executing beautifully on our first program. Okay, so you asked about the first program. Tell us about the program. Yep. Yeah. FIRCE-1 is a potentially pivotal phase II study of firi-cel, which has also been referred to as CRG-022. This is targeting the CD22 antigen initially in large B-cell lymphoma. In a phase I study with Stanford, they were targeting CD22 antigen in large B-cell lymphomas in patients who were either relapsed or refractory to CD19 CAR. Based on the strength of those data, and if we want to go into that, we can, Cargo has the IP for this from NCI, and so we launched our potentially pivotal phase II FIRCE-1 study with firi-cel last fall, and we've now dosed over 20 patients with impressive manufacturing success. There's a whole lot in getting to that point that this team has done, and I'm just incredibly proud of what we've been able to achieve. What I think really stands out here, if you know this space, is patients with Large B-cell lymphomas who are relapsed/refractory to CD19 CARs are very, very advanced in terms of their cancer. And these patients, there's about 60% of patients who are relapsed/refractory to CD19 CAR in this space. They are facing a dire outlook and prognosis. Median overall survival for them today, with no standard of care, is less than six months. To be able to offer another therapy that gives them another hope, chance at a cure, which autologous CAR T-cell therapies, we believe do, and based on the data at Stanford, which I'm sure we'll get into, this one looks like it has that potential as well. It's just. It's such an honor to be at a company that can potentially do that, and so that's what we're aiming to do, is to continue to execute on this trial and get interim results in the first half of next year and get this to patients as quickly as we can. Let's, before we think about what to expect and what is a great result in the pivotal, potentially pivotal phase II, let's revisit your view of the phase II-A data, phase I, phase II Stanford data. Okay. And tell us about how many patients and what the CR rate was in these high-risk patients, and when you last presented it, how much follow-up and what type of durability are you seeing with this drug? Okay. I'm so patient-centered, I just have to say patients with dire prognosis, because they're- Dire prognosis. They're wonderful patients. Absolutely. Yeah, yeah. But the outcome- It is tough. ... for them, it was- Yes ... really tough at that point. Okay, so the Stanford study enrolled and dosed 38 patients, and it was a phase I study. These patients, I'll just repeat it again, large B-cell lymphomas, relapsed/refractory to CD19 CAR, and this was sort of a Hail Mary study for them. They were really trying to give patients who they saw as being a patient population that was growing because they were using more CD19 CARs, and they saw this growing population of patients with just this very high unmet need. They're also very advanced, they're very sick, and so I want to describe these patients a bit. In their phase I study of these 38 patients, about a third of them were refractory to all prior lines of therapy. They just failed, failed, failed. 84% of them had high LDH, which is a strong negative prognostic factor for the CD19 CAR durability, I believe, but maybe also CR, but I know for durability for sure. So strong negative prognostic factor there. They were 10 years older on average than what we saw in ZUMA-1 with Yescarta in an earlier line of therapy. But 10 years is quite a bit older, and so it feels like it's not a real cherry-picked population in terms of these questions of fitness. Can you give CAR after CAR? So that's why I say this was a Hail Mary. What can we do for these patients? Can we manufacture and give CAR after CAR? That had been tried with CD19 CARs, and that had not gone well, right? So that experience was out there. Okay, so with that backdrop, these patients, in terms of results, had a 68% overall response rate. They had a 53% complete response rate, and now I can say with follow-up... Well, I should probably say safety, too. The safety profile looked favorable. Yes. Now, the treatment of CRS has evolved over time, so it's not surprising we saw really good kind of, you know, CRS compared to what you saw in ZUMA-1. Again, that, that's easier to treat now. But what stood out was the ICANS. There was no grade three ICANS in these patients. And so that's, you know, these patients that get Grade 1, 3 ICANS with whether it's Yescarta or Breyanzi, they get encephalopathic, confused. They go to the ICU for sure, and that's about $60,000 for that visit to the ICU. Patient burden, caregiver burden, you know, care team burden, at the hospital, so and then the, of course, the economic burden. So that stood out in a really positive way. So, you know, there's efficacy, there's CR- Yes. Now, is there durability? Yes. So now I'll give the latest update. The latest update from Stanford, now with about 30 months of follow-up, is in dose level 1, and dose level 1's the dose we're pursuing. Dose level 1, the median overall survival is 25.7 months, and there's only been four out of 20 patients, for the whole study, out of 20 patients who went into CR, only four have relapsed. Yep. There have been no new relapses since the last update at ASH. Yep. at the Feb- Yeah. The latest update's from February, and there have been no new relapses, so. I mean, I would almost look at it like- Yeah. Yeah, median survival is 26 months. But the way I like to look at CAR Ts is that you got a significant proportion of people who get a really long benefit. Yeah. And then, in this case, 50% of the people may not have such a great benefit, and that's gonna drive this part of the curve. That's correct. And so even though you might have 25.7, because it goes like that on the curve, the other part of the curve, even though that's the median, is gonna be continuing to be flat. And that's what you're seeing because you're telling me that basically every person in CR, for 16 out of 20, after 2.5 years, continue to be in CR. I'd just say the majority do. Yeah, majority. We know that the majority of the patients continue to have a durable effect. Yeah. So if you get into CR, which is the goal, is to, you know, for as many patients as possible, we wanna see them get into CRs with autologous cell therapy. And then you wanna see in these later stages, is it durable, like we see with the CD19 CARs? And that's what we're seeing. We're seeing a similar Kaplan-Meier curve- Mm-hmm ... which is what you just described with that nice plateau. Mm. For every patient, for all the patients in this that have achieved CR, there's no median PFS yet, no median OS. So- Mm-hmm ... so we know that that's continuing to be durable for the majority of patients. Okay. Yeah. So given those very strong results, you have initiated the potentially pivotal phase II. You last updated and said that there are at least 20 patients that have already been treated. You didn't give a number, but you said very successful manufacturing rate, and that you continue to execute very well. You're going to be continuing to enroll this year, and you've guided to an interim analysis on the study in the first half of 2025. What, why take an interim? What is the interim? What will that tell us? Ah, okay. So all of that is accurate. So thank you for sharing that. The interim analysis in the first half of 2025 we think is potentially very important to enable us to have discussions with FDA. Okay. So based on the Stanford results, which are so impressive, we wanna see if we can achieve something that's similar, and if we see that, that's very meaningful for patients. We don't wanna sit on these data- Okay ... longer than we would need to, to talk to FDA. So we wanna be able to open up that dialogue with them, and evaluate this at that time. I think it's also beneficial. I'll say there's a second benefit to an interim analysis. There's investments we'd wanna make that would really be pretty significant towards commercialization. The team at Cargo has extensive oncology and cell therapy and operating experience. We're seasoned leaders at companies where you really learn what it takes to lead and operate a company. And so we're able to take that experience, and we basically have a company that can do from engineering through development, through manufacturing, through commercialization of the company. But we're not really pulling the lever on the investments to be ready for commercialization until we have interim results. Okay. Makes sense. Yeah, presuming that it's all clear on the results, you can go ahead and prepare a budget and a plan to commercialization. We have a budget and a plan. Well, a budget and plan- We can, we can start executing on it. ... start spending it. Start writing the checks and go forward with that because it does take time to build that. Yeah ... and prep that. As well as maybe manufacturing decisions. I don't know, but- That's correct. Yeah, that's correct. We're using CDMOs today, and that's- Uh- ... that's public information, to manufacture our product. The good news is, you know, the CDMOs have just come such a long way since the CD19 CARs were first in their, in their, you know, pivotal studies, and so that's been really helpful to us. And as I said, we have impressive manufacturing success with over 20 patients dosed to date. So I think that does reflect well on the partnerships that we have. So what would be in the interim? What is the protocol for the interim? What is the interim trigger? Is it triggered by something? How much data? What do you see in an interim? Yeah, so what I've shared publicly, it's real, those are all really good, very valid questions. What I've said publicly is it's a robust sample with robust follow-up so that we can have these important conversations and make important investment decisions ourselves. It is absolutely triggered by a certain number of patients with a certain amount of follow-up. Okay. But it'll be meaningful. Okay. Yeah. Jefferies has their own estimate, too. I'm sure you- Number is- I actually know that you do, yeah. Now, I'm gonna guess 50 patients and three plus months of follow-up. That's our own Jefferies estimate. And now, when you say you want to open a dialogue with the FDA, does that mean that you think that you could potentially prepare that amount of data in the interim to file in combination with the Stanford data? Or it's like, "Hey, here's what it is," and the FDA says, "Great, awesome, finish the study with all 100 patients and do it, and then you could do it," or it's a rolling BLA? ... Could be any of those, right? So it all depends on outcomes. That's what we believe. We believe it depends on outcomes. I believe the result will be strong. Everybody on Wall Street believes it will be solid. So the difference between filing, you know, off on the interim versus complete the study, and could be the difference between, like, spring, summer, versus end of 2025. Keep us in suspense. I just like gazing at you as you ask these questions that are very good. Very good. Very good. Very good. Very good questions. I will work to get some more information out of you. But the key idea is that there's an interim. Now, one of the things I would also say is, you did a recent PIPE. We did. Tell us about that. Yes, yes. That just happened, like, a week or so ago. I actually had to look at- That was a surprise to me, actually. There's so much that happens at Cargo all the time- Okay ... 'cause we're just executing so well and so quickly, that I had to look at my calendar before I came in here to see. Was the PIPE last week? Was it last week? We closed it last week. Okay, closed it last week. Yeah. So, yes, we, as you know, went public in early November- Yeah ... of 2023. Yeah. Um- Very tough- That was a difficult week. Very tough time in the market. That was a difficult time in the market- Yeah ... but that week, in particular, was tough. Yeah. There were investors that wanted to come in at that particular week, could not. Mm. So we've had investor interest, really- Mm ... really high quality investor interest, dancing around us, I guess, or staying close to the story since then. We had a Q1 earnings release that was received favorably by the market, and we basically provided the updated data that I just shared with you from Stanford, from the cutoff date of February, so we just talked about that. And we also shared the update on the patients enrolled over 20 with impressive manufacturing success, so that was well-received and rightly so. We knew that it would be. But we got a reverse inquiry, and so that helped to catalyze this, and this came together in less than a week. Okay. Very pleased. I think the important thing to know is that $110 million, it was oversubscribed. The $110 million, the use of proceeds is to double down on what was originally coming out of the IPO, going to be a sort of a lean effort towards BLA preparation. Okay. Now we can do something a bit more robust. Like what? We've got a lot of confidence in this. We're just putting more resources towards it. We're not going quite as lean. And then the other one is CRG-023. We continue to make progress with this... Well, we may or may not get to that, but- Mm ... with CRG-023, it's an IND-enabling studies. We continue to make great progress. We're quite excited about what we're seeing, and so we're putting more effort there, more resources there as well. And then this provides us runway through 2026. Before this, we had runway to 2026. Okay, got it. Yep. Okay. So, one of the things that people ask about is, presuming all the data is positive, looks great, you can file, we believe that's plausible, how do you think about the size of this market? Because, from a high-level perspective, many people just say, "Okay, well, it's post-CD19." You know, if you take everyone who's getting Yescarta, which is a big drug, 30%+ of those people will get long-term CRs. That still leaves 70% of the market, so maybe it's 70% of a large market. How do you, how would you describe to people? You think this is a billion-dollar drug? Like, what, what do you... How do you think about the market opportunity? Could you go upstream? Maybe the market's getting bigger because more people are getting Yescarta earlier. Yeah. What would be the two or three things to think about? Yeah ... for volumes? So first of all, I'd look at CD19. For this initial indication- Yeah ...... I'd look at the CD19 CARs and what we expect for their use. And so, worldwide, like, they're continuing to grow quite a bit, and there's more and more approvals coming. They're also moving into earlier lines of therapy, and not just second line, but there's studies in the U.S. and elsewhere, as you know, in first line. So we're seeing that use grow, and since we're used following CD19 CAR, not by line of therapy, just following that- Yep ... as you see that use grow, as you just said, there could be a bigger market opportunity here. We're watching closely their strategy, and I'm, I'm really open about this. Their strategy to really increase capacity at the centers, get more centers closer to the community. We're watching these things because right now there's demand for these CD19 CARs, but there still are some barriers to all patients getting access. Okay. So we're watching that, and we're hoping that that will also fuel growth. And mostly for patients, 'cause again, the outcomes here for many of the patients are quite good. You said potentially 70% of patients relapse or refractory. We use 60%, but- Okay ... you know, I think that- Okay ... that, you know, there's a range of what we think that relapsed/refractory population is. Okay. But that defines this population, and by 2030, we believe that's about 7,600 or 7,700 patients, roughly- Okay ... in the U.S., the EU, and the U.K. alone, so I'm not doing the whole- Okay ... the whole rest of the world. And so that's a sizable patient population. Yeah, and the Yescarta- It, um- ... is around 400 something. It's a little north of there nowadays. No, north. As far as I know, yeah. So we, you know, plus inflation, but- Yeah ... maybe it's 500 by the time we get there for a substantial amount of people getting cures. But that's, yeah. Yeah ... that's correct. Yeah. It's in that range. So times 7,500, it's $multi-billion. Yeah, that yeah, as a, as a potential opportunity, and of course, we, you do, and we do, we look at, you know, can all patients, will they you know, still be fit? There's probably- Yes. Right? There are, there are things to consider. That's one, that's one question, too. There's competition, which I know. Competition. Well, we'll get to soon. So some people say: Can people do two CAR Ts? Yeah. Can you do two CAR Ts? Do people wanna do... "Oh, you failed one CAR T, you know, here, we're gonna give you another one." "Wait, what? You're gonna give me another one of the same thing that didn't really work for me?" For those people who, who did it, it didn't work for. Is there any biology reason as to why that wouldn't work? What would, what would you say to that? I mean, I'd say there's the patient's health and T-cell fitness are the two biological questions that a treating physician has to look at, and the patient has to consider. You know, doing this again. But what I would say- But versus the data. I mean, obviously- Yeah ... everyone who said this had got fatigue. Yeah, exactly. But what I will say is at Stanford, what they learned is that these are pretty advanced and- Yes ... sick patients. They're older, as I just said. Yeah. And so, you can do CAR after CAR based on the Stanford data. I think that answered that question. Now, I think the conversation with the provider would be... I won't be—I'll take it a different direction. I think it is, this is a patient who is hoping for a cure, and now when they get CD19 CAR, I'm hoping this conversation starts to evolve. There's hope. If you don't get a complete response or a potential cure here, there's another chance for a cure. Yeah. I hope the conversation is that, and I would expect it to be that going forward. Not that it failed. It was a- Not that it failed, and do you want to do this again? If it does not work, there is another option. It's like, there's another option. Do you wanna, do you... And look, if you take—I'm gonna do this with the Stanford data, but you take that 60% potential for a cure with... Or I should say hope for a cure, because not all patients that go into CR stay, but most of them do. Mm-hmm. Hope for a cure, with whether it's Yescarta or Breyanzi, and then you have another 50-ish, based on Stanford, percent chance of a hope for a cure. Yes. I should say hope for a cure- Yes ... with firi-cel. That's, that's about a 60%-70% chance overall for a cure, if I'm doing my math right. Okay. That, as a patient, sounds like that's worth going down that CAR journey. Okay. I've got two chances to get to cure, and it might be 60%-70% chance that I could have extended life. I actually get chills when I say it, because I've... It's fairly rare indication, but I've, I've known somebody who started on that journey and didn't have the option to go to firi-cel- Okay ... and didn't make it. Okay. And I just- Yeah ... I'm hoping for these patients- Yeah ... that more of them have this chance. Talk about the manufacturing as well. So again, assuming positive data, assuming you could file, talked about the market opportunity, for all cell therapy companies, Arcellx is a perfect example. They basically said, "We did the deal with Gilead," and Gilead said, "We did the deal with them," because there's no chance for that smaller company to be able to make thousands and thousands and thousands of samples a year by themself. This is a scale thing and a COGS thing- Mm-hmm ... and people like Gilead are experts in cell therapy and big pharma. So can you make this thing, or do you have to use a CDMO? Like, what happens? We're making it. Yeah. We have experts that are... We have... With CDMO. We have a lot of experts. Yeah. Yeah. But the CDMOs are doing a great job now. This is not, this is not where they were several, you know, many years ago now, when Kite was launching their first. So- Yep ... the CDMO model is working. We have impressive manufacturing success. We're doing it. We're, you know, the... So what I'm gonna back up a little bit. By the way, I think you have two CDMOs, or at least one? We'll have two at launch. Yeah. Yeah. So, and so this is a... So what's important to know about our CMC strategy is that we have basically had a nice foundation to start with, with what Stanford did. They used sort of a kind of all-in-one kind of model, which makes this easily transferable and easily scalable. Yep. That's helpful when you think about the path to commercialization. We've made some improvements to that process. Okay. That comparability package, the analytical comparability package, was submitted to FDA, and we got a safe to proceed, so that's helped us get where we are today. Yep. So all of that important work was done. Those improvements made this a commercial—a readily commercial, sort of, ready, commercial-ready process as well. Mm-hmm, mm-hmm. So we're putting our commercial process into our potential pivotal study. That's also a best practice that was learned from the first practice. What type of capacity could you have if firi-cel was approved in two years? We have enough capacity to get us through launch, and then we'll need to either bring on another CDMO or look at- Launch is, like, first year or two, or like, can you give us more quantifiable, like, capacity is thousands, so we're not worried about it? So since it's, I wouldn't worry too much about it because we can easily transfer this. We've done it now multiple times, and so it's so easily scalable- Yeah ... that we can add, we either can add suites where we are, or we can add another CDMO. So we've got multiple paths. We can also think about the right time to invest in our own manufacturing. So we've got optionality, is what I'd say, and we're—we've got enough capacity to take us through launch, and well before that, we can look ahead and get another, again, suites or CDMOs on board. What would it take to file in Europe? Do you have to have European sites? By the way, is this study global? No. No. That's, that's a good question. U.S. only. U.S. only. It's a U.S.-only site. Yeah. In order to be filed in Europe, where other, obviously, CD19 is approved in Europe, what do you have to do to get filed in Europe? So there is effort that we'd have to put forth for Europe. We do have the expertise on the team to do that. We're focused on the U.S. today. Yeah. So it's a good question. It's one of the reasons why we do talk to other companies and share our story- Yeah ... with other companies. Yeah. We'd be willing to partner in rest of the world. The real reason for that is we are very focused on the U.S., and yet, at the same time, because of this potential benefit for patients, I think it's quite important to do everything we can to get it to patients around the world as quickly as possible. I feel very strongly about that. While we can sequence this, right, as we build the company, and capital becomes more readily available to us, and we can prioritize the rest of the world, we've got the people and the know-how to do it, and we're keeping doors open to make that as fast as possible at that time. I do think a partner ex-U.S. would help us. What would they- Just asking. I actually don't know the role. Would they need to open sites and enroll patients, just to be clear? It is a longer-term thing. Yeah, so- You have to enroll and treat patients there. Yeah, do you have to... Yeah, that you've got to go in and talk to the authorities. You do need some site for manufacture, not manufacturing- Right ... but you need, you do need to have release there, and you're- Yes. There's certain things you need to do. Yes. Sorry, I'm not the deepest expert on this- I, I- ... because we've decided to prioritize the US. I think patients, probably, but certainly you will need a manufacturing site set up there because we're not really being able to ship it. You don't have to. You can ship. Okay. That's why we do cryopreservation in our process improvements- Ah ... from Stanford, so you can ship. I think you have to do release there, but I'm, again, not the best expert, so I don't wanna pretend that I am. We're gonna defer. Um, yeah. Later. Okay, and then, last question is, in the last minute, tease us about the tri-specific you have. Yeah. A lot of people are excited about CD19, CD22, or another company was here yesterday talking about that. Mm-hmm. What, where is yours? When could it be in the clinic? Yeah, I'm just, I'm so excited for patients that there's all these innovations out there. So our approach is a tri-specific, it's a tricistronic, actually. It's three separate CARs with three distinct co-stimulatory domains. And that's all engineered on one vector, and we've successfully done that. There's also a proprietary platform technology called CD2 co-stimulation, and that's been engineered into one of the CARs, and that addresses another mechanism of resistance called CD58 loss. Okay. And that's, again, proprietary, so that's engineered on. So it's a multi-specific, but it's also addressing multiple mechanisms of resistance. And so the other interesting thing to know is that these distinct CARs, these are new binders. So we underwent a campaign for about two years of working on this, of several thousand different binders we were looking at, and we've narrowed down to—CD19 binders are fairly easy to come by, same thing with 20. So we found the best out of a group of good binders, and we optimized- Mm-hmm. and found the best of those, too. We did the same thing for CD22. We tried to make a better binder and CAR than our own firi-cel, and we couldn't do it, not one. Where are you with this? Is it pre-IND? This is an IND-enabling studies- Okay. and we're actually... We started those studies last fall, so we're well on our way, and we're in the manufacturability right now, and we're just hitting off milestones. The team's getting more and more excited about this, and so hopefully in the nearest future, I'll be able to share timing of when I would expect an IND. Okay. Fantastic. Yeah. Thank you so much, Gina, for joining us here. Congrats on all the execution so far, and we look forward to more progress this year. Mike, always good to talk to you. Good. Thank you for your good questions. Yeah. Thank you, Gina. Thank you, guys.