Good morning, everyone, and welcome to the next session. I'm Michael Yee, Senior Biotechnology Analyst at Jefferies, and I'm really pleased to have up on the stage with us the CEO of CARGO Therapeutics, Gina Chapman. CARGO is a fairly recent IPO or so, but most importantly, has been executing quite well, raised a great amount of money, has had great stock performance, and is on the precipice of announcing important data coming up. And so we'd love for Gina maybe just to give a brief introduction to the audience about your drug and the data it's shown in DLBCL and the opportunity this could have for DLBCL patients. Sure. First, thank you, Mike, for having me here. It's great to be at Jefferies in London with you, and it was about a year ago that we celebrated our IPO during a really tough week. That was a tough week, but we did really well, so thank you to your firm for helping us get there. Okay, so I'm going to start, though, by saying that CARGO is a clinical stage biotech, and we're designing, developing, and delivering what we believe will be best in class, CAR T-cell therapies. We're really trying to design and focus on design with a next generation of CAR T-cell therapies as well. And so our lead program that you were just referencing is firi-cel in FIRCE-1, a potentially pivotal Phase II clinical study in large B-cell lymphoma, and specifically in patients with this first target indication in patients who have failed CD19 CARs. So this is a very advanced patient population. These patients have been either relapsed or refractory to many lines of therapy at this point, failed cell therapy, and now have a median overall survival of only six months at the point in time that they enter this study for firi-cel. So our Phase II pivotal was based on really strong data coming out of Stanford. We can talk about that if you want. But I'm excited about what this potentially can bring to patients based on the strength of those data. And to date, we have now dosed 57 patients. And I say that with emphasis because we only started dosing patients in September of last year, and we were in a safety stagger for the first three patients. So really, we only opened up the study to more sites and to more patients at this exact time last year. So it's been, I think, a testament to the expertise on the team as well as the interest in this potential therapy that we've been able to achieve that. So let's talk about that data because it gives people a perspective of how compelling the data is and sets some context for what would be positive data when the study reads out. I'd like to remind investors, you said clinical stage. I mean, I give you more credit than that. We're talking potentially pivotal study going on right now. And so describe briefly the published results of firi-cel in third line plus DLBCL and people who had failed, relapsed, or refractory prior CD19 CAR-T. So there's basically nothing left. There's nothing left. What were shown in that data? There's nothing left. Again, a median overall survival at that point of about six months, and at Stanford, in their phase one study with this construct, they call it CD22 CAR if you look it up. But it's firi-cel. We achieved analytical comparability to it for our study. They were able to achieve a 52% complete response rate in the 29 patients who received dose level one, which is the dose that we take into our potentially pivotal study, and now they have about three months of follow-up. It's 36.7 months, and they have a median duration of response or DOR of 23.2 months in those 29 patients. Now, of those 29 patients, 52% achieved a complete response. Of those who achieved a best response of complete response, that median DOR has not been reached. Right. So in summary, because I don't actually love to look at duration response for CAR-T just because half the people don't get a super compelling result. It's all about the potential curative nature of the people do. And I think most of the audience understands that because of the familiarity with YESCARTA, a multibillion dollar product of which there's a 35% CR rate and you mostly have a CAR-T. So I can translate that for you who doesn't like DOR, but it is so amazing to get that 23.2 months to get around the whole population when it's median six months. That's why I share it. So in those who had a CR, 75% of them were still in CR at 12 months. Right. So in that population. Half the population are getting CRs and essentially most all are now still in remission three years later. Yeah. If you're familiar with the CD19 CARs and you know their Kaplan-Meier curve and you watch sort of how they drop off from CR, you see a drop off pretty sharp, those who don't respond at all to three months. Then once you hit a six-month CR, it tends to be pretty flat. I might be doing, I don't know which way I'm doing it, but I think for you guys it's that way. We see the same curve with firi-cel from the Stanford Phase I data, and that's been quite compelling. These are people who have already failed the YESCARTA? That's right. Right. So given those results, also maybe talk a little bit about safety and tolerability. Yeah, there's one other thing I probably didn't say in the beginning and I should have. Firi-cel targets CD22 antigen. So that's a difference. There's no commercially available cell therapy targeting CD22 antigen. So that's an alternative antigen to target after patients have failed rituximab and other CD20 attempts as well as CD19 with CD19 CARs. So I think that's important. Now you just, sorry. Safety and tolerability. Safety. Oh, yeah. So I should mention safety always up front. It's so important for these patients as well. The safety profile looks really good. It's in many ways better than what you see with CD19 CARs. Our CRS rate is lower than what we saw with those. I will kind of caveat that by saying management of CRS has improved since the time they did their pivotal studies. And then, but what's really standing out for us is that the ICANS, immune effector cell-associated neurotoxicity syndrome, ICANS or neurotox, grade three is nonexistent in the phase one study, even at the higher dose that we didn't bring to our study. So we're just not seeing that at grade three. And grade three ICANS creates a real challenging sort of treatment paradigm or whatever for patients. They're encephalopathic. They're confused. They go into the ICU. This is also a burden for the healthcare providers. It's about $60,000 on average per visit for these patients into the ICU. So to have zero compared to 12% to about 28%, depending on which CD19 CAR T-cell therapy we're talking about, 0% is an advantage. It's one of the reasons that we're looking to go into earlier lines as a next stage for this program. The main reason is you can get better efficacy, as we know, from CD19 CARs to move earlier. That's the main reason. But if you can avoid this earlier, that would be an advantage for patients as well. Okay. So given the high efficacy and positive safety tolerability we've seen, tell us about the pivotal study. You had briefly introduced it in saying that you had enrolled 57, treated 57. So what is the total amount of patients and when would we get data and what is good data? Okay, so total number of patients is 101. Okay, 101. It's about 100. And that's similar to what Kite did in their study. They had a single arm study. They received full approval, as did BREYANZI from BMS for their similar study designs. So that's pretty typical. And we are on our way to interim analysis with the momentum we've seen in enrolling patients. We're on target for first half of next year for an interim analysis. And yeah, really excited, looking forward to that. What does an interim analysis entail? Is that an agreed upon? It's in the protocol. And by the way, when you say 101, like I'm not sure if there's something specific about that number, but this is all discussed with the FDA. You know, it's all statistics. Statistics. There you go. Yeah. And so how did your team define an interim? Why are we taking an interim? And what is a good result on an interim? Okay, so I'm going to do the why an interim first. Why an interim is because, look, the results out of the Stanford study are really compelling for patients. These are patients whose lives are at risk. It's pretty dire, as I've already outlined. Depending on the strength of these results, we want to talk to FDA as soon as possible and figure out what the path to approval is and hopefully, right, move forward as quickly as we can for these patients. That's the why. And then the. So because you want to have the opportunity to talk with the FDA and see if we can get this going as fast as possible. As fast as possible. The what is, you know, it's to be determined by the strength of the results. That might not be as interesting of an answer for you, but that's the truth. We need to see the results to figure out what we need. What is a good result? What is a compelling result to CARGO that would say, wow, we got to talk with the FDA and the FDA could take this forward? Yeah. So look, the bar set by Stanford is a hopeful result. And we've designed the study very similar in terms of inclusion exclusion criteria and similar to what Kite and BREYANZI had for their pivotal studies for full approval. So we did that. So I think we've done everything we can to hope for patients that we get a really strong result like we saw at Stanford. But the truth of it is this median overall survival of six months sets the bar pretty low. And I'm not trying to do that. We want the best for patients. But what that means is there's a really wide range of what could be very compelling with FDA. It's another reason why we need to see the data. We need to base our discussions on that data with FDA and determine the path forward. From a fundamental perspective, I would say most of the investment audience understands that if there are very few, if any, approved therapies post CD19 CAR-T, then that presents an unmet need for a dire population. The results that we're seeing at the Stanford phase one that has been published is a 52% CR, and those patients all had failed prior CD19 CAR-T and transplant. Correct me if I'm wrong. Both. Those who could have transplant may have failed transplant, yes, but not all. All of these populations were studied and there were very strong and consistent results across that forest plot in all of those patient populations, including double refractory. That's right. We're 33% CR. That was more, and sometimes more than double refractory. That was a third of the patients were refractory to all lines of therapy. Right. Okay. So all lines of therapy, which would include like chemo and other stuff. Everything. But it had no response to CD19 CAR-T, no response to transplant. This is a dire patient and they get a CR, one third of them. So given that that was a pretty dire population in the Stanford study and you saw 52% CR, are there reasons to believe that this population in your pivotal study, realizing the minimum is just having failed CD19 CAR-T, is there a reason that these patients would have failed less therapies such that it'd be slightly less dire? Therefore, the result, you'd have confidence the results could look fairly similar. Analyst estimate may be better, but you feel confident the results will be strong because it's not a worse population than that. Yeah. So what's changed since Stanford enrolled their patients, which is what you're alluding to, is that the CD19 CARs have now been approved in a second line. So that could mean that these patients are receiving firi-cel in our study in an earlier line of therapy. So that means they could potentially, their health status could be better. Their T-cell fitness may be improved from what Stanford saw. So that's the hope. So yeah, so everyone gets R-CHOP. That's first line. In second line, back in years ago when the Stanford experience, if you go back years, they would have failed transplant or have moved on from transplant. And then they would have gotten CD19 CAR-T here. Since many people get CAR-T in second line and we skip the transplant, then they may be one less line, we've seen one less line, but have still failed CAR-T. So you feel that these patients should be in a good position to have a strong result for your therapy? Look, we certainly hope so for them, and that does lead us to be very optimistic about what we might see. Two final questions about this. One is how I've been asked about the fact that there is CD20, CD3 bispecific from Roche, who was just in the other room. We were just hosting them. And they have 30-something percent CR after failing CAR-T. So technically, as I said, minimal therapies available. There's one. Like, is that a compelling product? Do you need to be better than that product? Wall Street would like to see strong results. What to you is compelling? Because the better the results, the more commercial opportunity for you, for investors. That's right. That's right. That's right. So the bispecific T-cell engagers have been approved and accelerated approval and have been third line. And that's in CAR-naive. And then they had a subset of patients in that study that were CD19 relapse refractory. That was 52 patients. Don't get the 52s mixed up with our CR rate. That's the same 52. Yeah, don't confuse those two. But that's a subset. In those patients, they did achieve a 37% or 38% CR rate, but that did diminish down to 20% over time. Like after a year? About a year later, they were at 20%. A big portion of those fall off after a year. They do fall off, so the KOLs, I speak to what they think about when they think about what's the durable response you might see for a period of time. They're not sure how long yet. With a bispecific, they're thinking 20%, so if you talk to a KOL, you're going to hear 20%. And that's why, so with that in mind, it's important. That's a pretty interesting frame. Like when we talk about CRs, like in this setting, people are thinking about durable CRs. We've also been trained by that from the SCARA. So to say 37, but only 20 something actually is after a year. Right. Okay, got it. So I look at that as, you know, those are available. Now, one important thing to think about, and KOLs bring this up all the time, especially those who are really, I'd say, proponents of using a cell therapy first. And so, you know, we want to see cell therapy followed by our cell therapy first. Because of convenience. They want to give a patient the very best chance at a durable CR or a potential cure. That's their goal. The other thing that's going on, though, is these bispecific T-cell engagers I'm drawing with my hands. They want to see the highest chance for a cure. But what's going on is the bispecific T-cell engagers require dosing over time, multiple doses. And there is toxicity, continued toxicity as you dose. Remind me, is that a monthly or a week? Oh gosh, I'm always, I'm sorry. We need to check on that. But it's chronic dosing. Chronic dosing. I can't remember if it's every six weeks or every four weeks. Sorry, and EPKINLY versus glofitamab, I think there's a difference in the dosing there, so this is continued dosing regularly over time. These patients, many of them for glofitamab and EPKINLY, they still are going into the specialized treatment centers for this. This hasn't really made it into the community yet. That's the goal. That's because they're CRS. That's the goal. That's their goal, I should say. Their goal is to get to the community setting and to be used in earlier lines. That's what they're trying to do with their strategies. And they're very open and talk about that in their earnings calls. And so what's happening right now is I think in terms of what the original consensus expectations and forecasts were, they aren't quite reaching that level of penetration yet. However, we are seeing their growth. So yes, this is a therapy that can be used after CD19 CAR failure. The question is going to be, what's that durable complete response? What can we achieve? And then what does it need to be to be, in our opinion, you know, the therapy that's preferred sequentially to a bispecific T-cell engager to go on CAR after CAR? So if you start with a CD19 CAR, you get about a 40% CR, and then you go to firi-cel after that, and let's say you get another response that's durable at around the same rate, that combined potential for cure is far greater than a bispecific T-cell engager, right? That could be a very compelling argument to use cell therapy. That's what I mean. Some people will say. Pending Stanford data, right? Sure. But some people say, well, Mike, the opportunity is a fraction. I'd say a majority of the people who take CD19 CAR-T. You can go do the math since we also just hosted Gilead. They're doing about $2.3 billion next year for YESCARTA. So of those people, 65% of those people are not going to get obviously a durable CR. So 65% of $2.3 billion is still multibillion. And then are those people going to want to take a second CAR-T if they didn't get a response to a CAR-T? So that's a great question. You know, it's patient dependent. We've been very encouraged by the rate at which and the momentum we've had dosing, right? So the answer, I think, is yes for many patients. Patients seen good impact and you've been enrolling patients. The interest from the investigators, the engagement here and the ability to have patients come on and be interested in this has really been telling. So I think the answer is yes. Now, patients want a chance at a cure, and I think if they can receive, it's more can they receive a second CAR? Is Is their health status such that they can? Right? It is a process to go through. That's a good question. In a model, how is that if a small fraction of the patients may not be eligible for another CAR-T because they are fairly frail patients? They are fairly frail. But you know, again, Stanford accepted these patients. We've designed our study too. We have frail patients in our study. But I think the question is going to come down to. It's well tolerated. There's going to be, let's be honest, there's some patients for which their disease is progressing so quickly that it might not be an option for them. Or they may be too frail or not interested in undergoing apheresis and lymphodepletion. Again, that's the question for the patient. That's true. So let's say the results are strong. Analyst estimate at Jefferies says, you know, 40%. We'd like to be above Roche CD20 and don't necessarily have to replicate Phase I data of 52%. And let's say there's also strong, you would engage and call up FDA and see what the next steps could be. Maybe there's a chance you could start a rolling BLA, but in any case, you're going to engage with the FDA. Correct. Okay. Now, when that occurs, do you plan to commercialize? So talking about that, plan to commercialize in Europe. Would you partner this thing? Could be acquisition candidate? Right. It's important to us. The main thing that's important to us is to get this to patients as quickly as possible, again, pending strong results, and we have the expertise and the experience in commercializing, launching products, both in oncology and cell therapy at CARGO. We have a very small team right now just laying out the plans to do that and getting the delivery systems very important to have in place before a BLA. That's part of that design goes into the BLA. We have those experts on the team today. We've got plans, pending data, to really build this infrastructure within the U.S. This is a great beachhead type of launch opportunity for us because it's a known population. They're identified. We know where they are, and the paths have been paved essentially by both YESCARTA and BREYANZI and KYMRIAH. Can I ask a tough question? Yeah. First of all, given your prior experience in commercial, running that at Genentech, Roche, you have certainly the experience to go build that and to deliver a successful cancer therapeutic and commercialize that. Then I would also say many investors would say it's very difficult and capital intensive to launch a CAR-T by yourself to field a sales force. Gross margins on CAR-Ts are not super awesome at the start. And you're really going to go do Europe? So, I didn't say, and we're going to go do Europe. So in the U.S., it's a great beachhead for us. It's actually quite manageable for this particular indication for us to do that in the U.S. We've run the numbers. It's in our budget and it's in our runway to be able to prepare for that. And then in terms of Europe, I started out by saying we really want to make sure we can get this to patients as quickly as possible. For a company like ours, doing that sequentially is possible, right? But it'd be better for patients if we found a partner to help us outside the U.S. We could go a lot faster with a partner. And at what point does that make sense? That's after data. That's at what point? And is a partnership good? Like, well, yeah, again, analyst estimate, you know, partnership discussions can lead to other things. So look, our vision for CARGO is to build a fully integrated leading cell therapy company. Of course, in this, I'd say for patients, if you think about patients and following science, there are other companies that probably would have similar sort of visions and strategies, same values, patient centricity, follow the science. There could be very compelling ways to combine efforts where there's synergy in achieving what we're trying to achieve. Our door is open and we're talking to partners all the time about where their science is, where ours is, and what's possible. We have a very experienced BD team. And so we're scanning the environment all the time. So you're looking at this. You're in talks with discussions on potential. We're sharing our story. They're sharing their stories. They're following the region. They're following it. region. They're following it. region. They're following it. We're waiting for the data. We're waiting for data. We're just waiting for the data. So that will come in the first half of 2025. That leaves me with the last two minutes to say, well, look, if that's the case, tell me because you have a second CAR-T that could be superior, but it's a tricistronic, and is that going into the clinic? CRG-023 is a trispecific designed on a single vector. It's a tricistronic and that is unique and differentiated. We believe it's the first of its kind tricistronic. Okay. What are the three? So yeah, so independently expressing CD19 CAR, CD20 CAR, and CD22 CAR, all independently expressing. We have an IND that we expect to share in the first quarter and plans for first patient dose next year. We'll know more about what the timing of that is when I can announce an IND. Really excited about it. It is well differentiated. I think the design really helps kind of highlight our cell engineering expertise and capabilities at CARGO. We ran a binder campaign. I don't think others really take the time to do this, but we ran a binder campaign going through thousands of binders to optimize CD19, CD20, and we tried CD22. We ended up landing with the binder we have, m971 for firi-cel. But for CD19 and CD20, we were able to find binders that could optimize for antitumor activity expressing independently compared to benchmarks. And then we also optimized how we combine them, the order. So what we're seeing is that you can express these binders independently and we're seeing antitumor activity even in the face of continuing to challenge with tumor, sustained antitumor activity. I say this. So that'll be at ASH. We have a poster at ASH. I say that because for those who are not following, there's a small little company named Janssen. J&J did in-license a CD19, CD20 CAR-T. They're developing that. You have a CD22 and you have a, what'd you say? It's a tricistronic. T ricistronic. All on one vector. I say that because Gilead just told me they have a bicistronic. They have a bicistronic. Bicistronic. Yeah, on one vector. They're doing CD19, CD20. That's right. Sort of a duplicative version of the Janssen one. You have a tricistronic. Yeah, and our hypothesis is that going after three antigens is better than going after one or two. And our preclinical data, and again, since we're almost out of time, I'm watching your clock, that's at ASH in a poster and I think it's quite compelling. Thank you very much, Gina. Looking forward to the upcoming data in the first half of 2025 and continued execution. Thank you, Mike. I appreciate it. Thank you.