All right, is this working? It is. Good morning, everyone. We don't have our moderator yet, so I'm going to kick us off, which I'm delighted to do. I was going to thank JP Morgan and Brian for this invitation to present the CARGO story today and provide you an update on what we're doing. And I'll just have to thank Brian once we sit down to do the Q&A together. He would have introduced me, but I'll do that myself. I'm Gina Chapman. I'm the President and CEO of CARGO Therapeutics. We're a clinical stage biotech and a leading innovator in cell therapy. You want me to continue, Brian? Yes. All right. Excellent. Please reference these forward-looking statements regarding this presentation, and we'll get started, so at CARGO Therapeutics, we are absolutely united and very inspired by our mission to develop a next generation of best-in-class and potentially curative cell therapies for people with cancer, and in the next 20 minutes, what I'm going to do is highlight impressive progress we made in 2024, advancing what are now three programs, two clinical-stage and one just entering sort of an IND-enabling stage, as well as the key milestones that we're expecting to deliver on this year in 2025, so let's get started. Our vision. I just walked through our mission, but our vision is really to expand the patients who can benefit from our therapies, as well as cell therapies with curative potential. Our lead program is firi-cel. This is an autologous CAR T- cell therapy targeting the CD22 antigen. We're in a potentially pivotal Phase 2 now, enrolling patients with interim results expected in the first half of this year. We have CRG-023, which is an autologous CAR T- cell therapy that is targeting CD19, CD20, and CD22 antigens. This is a trispecific, tricistronic therapy, and we have, well, we're delighted to share, we've just recently announced on Friday that we've cleared our IND with FDA, and we'll start our Phase 1 study by mid-year. For the first time, I'm also announcing that we have a novel allogeneic program that we're developing at CARGO. This is a universal allogeneic enabling vector for CAR T. Our lead vector candidate selection is expected, once again, in the H1 of this year. Innovation and execution are advancing these programs, and this is underpinned by robust cell therapy expertise and capabilities at CARGO. I want to emphasize and just really acknowledge the transformational achievement of autologous CD19 CAR T- cell therapy in relapsed/refractory large B-cell lymphoma. For the 40% of patients, roughly 40% of patients who achieve a durable, complete response, this is life-changing. These are potentially curative therapies. That is fueling growth, along with approvals in earlier lines of therapy across geographies. Furthermore, patient access is starting to broaden the ability to provide these therapies as more treatment centers offer CAR T- cell therapy and as other access challenges are addressed. Our initial target indication for that lead program, firi-cel, are the patients, and it's a growing number of patients, who are CD19 relapsed/refractory. And with that growth, we expect this patient count to rise to 8,000 patients by 2030 in the U.S. and the EU5. It's a high unmet need group of patients, again, and this is growing. We also estimate that about 39,000 patients will be CAR naive by 2030 in those same geographies. And with pipeline management, lifecycle management, we expect to be able to address some of these patients as well. So firi-cel, with this program, we aim to address initially the unmet need of large B-cell lymphoma patients who are relapse refractory to CD19 CARs by targeting the CD22 antigen. That high unmet need population I was just talking about is denoted in this orange circle on this Kaplan-Meier curve of progression-free survival with a CD19 CAR in relapse refractory large B-cell lymphoma. And these are data from a pivotal trial. As you can see, about 40% of patients have a durable, complete response, and you see that nice plateau on the Kaplan-Meier curve that shows this has curative potential for many patients. However, there are still 60% plus patients who do not achieve that durable, complete response. This population has a very high unmet need. Their median survival is only five and a half months. So with this growing unmet need, Stanford was out in front in identifying this, and they designed a Phase 1 study with firi-cel to evaluate efficacy and safety in this population. Stanford has presented these data at previous conferences, and they also published this in The Lancet last year, so this is widely available. The patients they enrolled, they enrolled 38 patients in the study, and the patients they enrolled were a median of 65 years old. They'd received a median of four prior lines of therapy, and 84% of these patients had high LDH, which is a marker of high tumor burden. So these patients are heavily pretreated and have advanced disease, very challenging to treat. Stanford studied two doses, dose level one and dose level two. Dose level one is 1 times 10 to the 6 CD22 CAR T- cells per kilogram. That's the dose that we brought forward to our Phase 2 study. So those are the data that are summarized here. Let's start with efficacy on the left. As you can see here, the median follow-up at this point in time, and this was just presented by Stanford at the most recent ASH meeting, is 38.9 months, 39.8 months. I don't have my glasses on, so apologies for that. 38.9 months. The overall response rate is 66%, and the complete response rate is 52%. The 12-month duration of response is 73%, and the median overall survival is 25.7 months. Importantly, the median overall survival, the median OS, and the median duration of response has not been reached for those patients who achieved a complete response, and you can see the overall survival for the patients who achieved a complete response on the graph and the top Kaplan-Meier curve in blue. Toxicities associated with CD19 CAR T- cell therapies, you can find those on the right-hand side of the slide, and what stands out and what you can see is that this tolerability, this profile is relatively tolerable as compared to CD19 CARs in an earlier line of therapy in patients with large B cell lymphoma. I do want to speak to the immune effector cell HLH-like syndrome. This is associated with CD19 CAR T- cell therapy and firi-cel. 7% of the patients in this study did have IEC-HS. This was monitorable and managed with anakinra steroids in this study. I think it's important to note that at dose level two, there was a higher rate of IEC-HS. It was 34%. That's the reason that, and based on comparable efficacy, the reason that Stanford then stopped enrolling in dose level two, enrolled in dose level one for the duration of the study, and why we've taken dose level one forward in our Phase 2 study. Now let's talk about our study. This potentially pivotal Phase 2 study is a single-arm, multi-center study, and we're evaluating firi-cel in a similar patient population in terms of inclusion and exclusion criteria as Stanford. These patients have relapsed/refractory large B-cell lymphoma. They are relapsed refractory as well to CD19 CAR in all of the cohorts, and they have CD22 expression at any level. Cohort one is, as I just described it. Cohort two is the same population as cohort one and cohort three, but this is to evaluate any non-conforming product or dose, and the opportunity here is to potentially expand our specs with the product. Cohort three, similar to cohort one, patients with relapsed refractory LBCL to CD19 CAR, as well as they could be relapsed refractory to the bispecific T cell engagers, so we're enrolling 81 patients or dosing 81 patients in cohort one and 20 patients in cohort three, and there is no target for cohort two. We enrolled our first patient in August of 2023. Last year at this meeting, I announced nine patients had been dosed. And so I'm very pleased this year to announce that we've now dosed 71 patients as of the end of December. Just incredible execution by the team and also great engagement by our sites, by the clinical trial sites. We've also achieved strong manufacturing success, and that continues. We're looking forward to interim results in the first half of this year, and our team is just incredibly proud of what we've been able to achieve through 2024 to get us to this point where we are remaining on track. Now, in line with our mission to design, develop, and deliver a next generation of best-in-class cell therapies with curative potential, we designed CRG-023 to deliver multiple beneficial transgene cargo from a single vector. And this was inspiration in part for the name of the company, was this idea. This has now advanced from idea to where we can show that we've been optimizing in this design many aspects of a cell therapy for patient benefit. Through sophisticated engineering solutions, we're addressing several of the challenges associated with poor responses to cell therapy, inclusive of antigen escape, loss of co-stimulation, and lack of T cell persistence. We'll start with antigen escape. Our trispecific CAR T- cell product expresses three specific chimeric antigen receptors, and it does this simultaneously and independently. In addition to address loss of co-stimulation, we've engineered a novel CD2 technology with our CD20 CAR. This was based on observations that loss of CD58 was associated with poor responses to CD19 CAR therapy. Finally, lack of T cell persistence, we have a number of ways that we're addressing this. We're using new human binders. And in fact, we ran a binder campaign in order to find what we've hoped will be, and we expect to be, superior binders to those that are already used and often recycled in cell therapy design. And so we've got a new binder for CD19 and CD20. We also ran a campaign to see if we could find a better binder than M971, which we're using in firi-cel and in the intention to use it here as well. And we didn't find a better one, so we are using the M971 binder as well, also a human binder. We optimized the CAR design, and what we did there is we essentially screened over 1,000 constructs to optimize that, as well as optimized our manufacturing process, which is portable and has basically an optimal profile that we've designed that's portable with optionality built into it. We've employed multicistronic engineering that allows us to get this potentially beneficial CARGO, transgene CARGO, onto a single vector and allows for that simultaneous and independent expression of the CARs. With that design, we went to work and we did a number of experiments, and the preclinical data were recently presented at ASH last month by our team. I'm excited to just share a small sample of what's in that poster presentation with you here today. As you can see here on the left, there's a serial stimulation assay that was done, and this is testing the ability of CRG-023, as you can see in orange, as well as monospecific CAR controls in the blues and purples to test the anti-tumor activity with repeated challenge by tumor cells. You can see here the superior sustained activity of CRG-023 compared to those monospecific controls. This is also with a notable lack of T cell exhaustion and, again, in the face of this repeated challenge from tumor cells. Additional key results from that poster presentation and available by accessing that presentation are that CRG-023 T cells maintained memory profile in a serial simulation assay. Furthermore, this confirmed for us that design does matter, and it was worth the time, the investment for us to really hone in on design and engineering here. Each CAR sustained anti-tumor activity in the presence of a single antigen expressed. Also, differentiation was further demonstrated by robust in vivo anti-lymphoma activity at low CAR doses. Safety is very important, especially when you're designing something as novel as this, and we were pleased to see that excessive cytokine production or expansion were not observed. We're excited to be moving into this Phase 1 study. Once again, our IND was cleared earlier this month, and Phase 1 enrollment is expected to initiate by mid-year. Our opportunity here with CRG-023 is potentially to move beyond just large B-cell into a broader range of B-cell malignancies by targeting these three antigens. Our strategy, though, is to demonstrate best-in-class potential through a Phase 1 open-label, multi-dose escalation study in patients with third-line plus large B-cell lymphoma, including CAR-T naive patients. We will start with a low dose, a low flat dose informed by the preclinical data that I just spoke about. Our intention is to obtain proof of concept inclusive of efficacy or safety and efficacy both, and then move as quickly as possible into earlier lines of therapy in large B-cell lymphoma and to other indications for more benefit for patients. The rapid progress we made on the lead construct to IND submission in less than 12 months was supported by robust CMC and clinical development capabilities at CARGO, and we're quite proud of that. So now it's also my pleasure to announce, as I said, for the first time, a novel allogeneic platform that's been under development at CARGO. This is a universal allo-enabling vector solution that is engineered to limit rejection and enable conversion of autologous CAR T- cell therapy for broader patient benefit. Our innovative and differentiated approach is designed to address cell therapy challenges that exist today. I think importantly, I'm going to start with an allo challenge here because importantly, this one matters a lot. Allo approaches today must avoid immune rejection long enough to achieve a durable response. It's a key challenge, and we need to see this in more patients. We've got some great news just recently, but we need to see this in more patients, especially patients with cancer, and then in autologous cell therapy, efficacy and durability, there's still opportunity left for patients who are not achieving those durable complete responses. And in part, this is due to the poor quality of T cells derived from sick patients. In addition, broad availability for patients to access these therapies is still challenged. Scalability remains an issue, so our solution is illustrated on the left-hand side of this slide, and I'm just going to walk you through it so I can really bring this to life for you. The CARGO universal allo-enabling vector paired with a CAR vector, new or existing, co-transduced, and using enabling, essentially, and leveraging current drug product processes converts to an allogeneic CAR T- cell therapy. The opportunity here is significant. By pursuing this approach, you can maintain efficacy, durability, and safety of autologous CAR T- cell therapies while broadening their availability to many more people who might benefit. This progress that we've made obviously supports an amazing opportunity, but I want to show you, and I want to tell you how much data, preclinical data, really supports already this idea and what we've been working on now for three years at CARGO. The sophisticated engineering to pull this off is substantial, but the solution is elegant, and it's actually surprisingly simple. I'm just going to walk you through the single vector design now. Our team has been able to eliminate MHC II and reduce MHC I by limiting T cell and NK cell rejection. In addition, they're limiting CD8 activity against residual MHC I, and they're reducing the co-stimulation to limit NK and T cell activation. By doing these things, this is enabling persistent response. Really, really critical. It was one of the key challenges with allo therapy. Also very important in allo solutions is to address safety risk with graft-versus-host disease. A redundant method deployed at CARGO is downregulating TCR to prevent graft-versus-host disease. A lot of progress made to date. We've advanced several lead vectors engineered to limit immune rejection. We are demonstrating safety in vivo and preventing graft-versus-host disease without gene editing. We are preserving CAR activity with co-transduced GMP CAR vector. And we're demonstrating feasibility of co-transduction that I talked about to produce allogeneic CAR T- cells with high purity and in multiple doses at meaningful manufacturing scale. Like I said, we're sort of already leaning into IND-enabling work. We're doing this with several vectors, and we will choose and select the lead vector candidate in the first half of this year. The team are quite inspired and excited by the progress that's been made, and what I will do is highlight just a few of the experiments and data from those preclinical experiments for you. Otherwise, it just sounds like maybe a dream or a wish. So here we go. In a peripheral blood mononuclear cell rejection assay, we're basically demonstrating this novel engineering limits allogeneic rejection, and you can see that here. In orange is our allo solution, and this is compared to benchmarks, TRAC knockout and TRAC plus B2 M knockout, and you can see that our allo solution has superior survival compared to those benchmarks. In an acute xenograft graft-versus-host disease model, and this is an in vivo model, and it's also a high bar model, we're demonstrating that redundant method, that approach we took to knock down TCR, prevented graft-versus-host disease. Hopefully, you can see it. You can. The orange line is hugging that zero graft-versus-host disease score. Very compelling, what we've done in a serial killing assay where we challenged the CAR T- cells by adding tumor cells every three to four days, so really challenging that CAR T- cell, is we've shown what is comparable activity for our CAR T-cells, and I'll walk you through those in a minute, produced in both an autologous and an allogeneic process. What you can see in orange is the co-transduced vectorized allo CRG-023. That's in orange, and that is hugging CRG-023 autologous product. We're really, really delighted with what we were able to achieve here. Remember, CRG-023, that's a single vector with a lot of CARGO on it. We took one of the more challenging products you could probably co-transduce with and create an allogeneic product in this experiment, so that's the one we're showing you. All right, we're excited about what this could mean for patients. We believe that many more patients could benefit from this platform and from this technology, and that's what CARGO is all about. In summary, strong execution, experienced leadership in oncology and cell therapy has helped us advance three novel CAR T- cell therapy programs to key milestones that we're expecting in the first half of this year, positioning us as a leading innovator in cell therapy, and we see this growing market opportunity with potential for so many more patients to benefit from potentially curative cell therapies. We have a strong cash position of $368.1 million as of the end of last year and cash runway through 2026. In closing, I really need to thank our team at CARGO. They are striving each and every day to advance these programs and bring potential curative benefit to patients in their fight against cancer. Thank you for your attention. Brian, at the beginning, I did thank you for this opportunity to update everyone on our CARGO story. Thank you. You and J.P. A lot of traffic coming to this side of the conference. So let's start the Q&A. For those of you who are in the live audience, if you have any questions, you can raise your hands. We have a roving mic on the floor, and for those joining us virtually, you can also submit questions on the portal. Gina, thanks for joining us. Lots of updates here across the board, but let's focus on firi-cel, which is your lead program that we're going to have an interim look sometime in the first half this year. Can you just kind of give us a sense of how the enrollment has been compared to your internal projection? I think now you have 71 patients dosed. Just how does that compare to your initial projection? Is that in line with how you initially thought of the pace of enrollments and just how confident that we're going to see interim data within this first half window? Sure. Thanks for the questions and for this opportunity just to catch up with you as well. I'm delighted that we're on track. These are the projections and the guidance that we provided a year ago. So we're just executing really well, and I attribute that not only to the team's efforts, but also to the engagement with our investigators. One thing I can share is that we've got most of the sites, the vast majority, quite engaged and dosing more than one patient, and I think that's really helped with the enrollment and the dosing. Yes, we're on track for sharing interim results in the first half of this year. Quite confident. Great. Heading into the data, I think we're going to discuss a little bit more about what to expect, right? But as we are heading into this readout, how should we think about what to focus on? Maybe just one is, what should investors focus on in terms of efficacy? And then also, how should we think of the bar for success for this upcoming study readout? Okay, yeah, good questions. Look, we all, I think if you're familiar with cell therapy and what to expect in large B-cell lymphoma, I think we're all most interested in six-month durability data. The intention of this analysis is to actually pull a substantial sample in order for us to have a discussion with FDA with at least three-month follow-up. So that's the focus of defining sort of what interim analysis is. We're hopeful, and it kind of depends on that trajectory of the dosing that happened kind of earlier last year. We're hopeful we'll have a sample of patients with six months durability, but we don't know yet. So until we start to collect the data for those patients who've achieved three months, we won't know what that sample is for those who've had enough follow-up and we can get scans in for six months. So we'll have to stay in tune with that. But what we need to have a robust discussion with FDA, we're confident we'll have in the first half of this year. In terms of the bar you said. Yeah, just six months durability is, I think, not just from a regulatory standpoint, there's also, I think for investors, it's also important to kind of use that as a benchmark to predict how it's going to look like longer term, right? So how should we think about just what you need to achieve at the six-month or even at the three-month time point? Yeah, I'll just explain that a little more. The reason six-month durability is so important as we look at CAR T- cell therapy is in large B-cell lymphoma, I shared that Kaplan-Meier curve of a CD19 CAR, and you could see that plateau that started to happen right around the six-month time point. So that's what we've come to expect. So that's why I referenced that. And that's also important when you look at sort of what we see as the potential bar. At Stanford, that sort of six-month CR rate, the initial CR rate was 52%, and the six-month CR rate was somewhat lower than that, but not substantially so, so I think that's one bar. The other one is that median overall survival of five and a half months is very, very low, so without treatment or without a potentially curative treatment, patients are not doing well. So that's a very low bar, and then since Stanford conducted their study, the bispecific T-cell engagers are now available. They were approved through accelerated approval in CD19-positive large B-cell lymphoma and now in second-line. So those are available, but what we saw at ASH is that you don't get that plateau that you see with the CD19 CARs. You continue to see erosion, and you just don't get quite the durability. They didn't share data at ASH in the CD19 relapsed/refractory population, so I don't know where that heads, but we do know that it's at least 20% or lower. So you've kind of got this five and a half months overall survival with very poor outcomes, and then you have something probably below a 20% durable CR rate with bispecific T-cell engagers, and then you have what Stanford achieved. Does that help? Yeah, that helps. And maybe just, I think another side of it is also kind of manufacturing readiness and also the vein-to-vein time. Can you address those? How does the vein-to-vein time look today? And as we think about potential commercial launch in the near term, how could that look like? And also the potential capacity to meet the demand? Great. Okay, really good questions. First of all, let me just say the impressive manufacturing success rate we've been sharing continues, and it's really something we're quite proud of. And we're just pleased for the patients that we're able to deliver as they'd hope a product for them that, again, gives them that hope for a potential cure. So that's been wonderful. The vein-to-vein time is also what we would consider in a competitive range. From AIF to product release, it's 20 days, and that's sort of the time that those events or that time period that we have more control over. So we're really pleased with that. That's right where we'd want it to be. And it's also predictable and reliable, and that's what physicians who are treating these patients really want. They want to be able to predict and rely on us. So that's great news. We have three CDMOs. In terms of your other question about readiness, we have three CDMOs, one for vector and two for drug product. We're quite confident in the ability to support completion of Phase 1, our Phase 1, our Phase 2 study for firi-cel, a potential randomized controlled trial, if that's something that we need to pursue or want to pursue, launch, and up to two years of commercial supply. So we've got that covered with those. We have successfully produced, and I'll just tell you why we're confident. We've successfully produced full-scale GMP vector batches through the vector CDMO, and then over 70 drug product batches with our drug product CDMOs, again, with that impressive manufacturing success. So that's where the confidence is coming from. The other thing that gives us confidence that we can scale, and I know this has been a challenge for other companies in this space, is our process is portable and it's easily transferable. That enables us to adapt pretty easily, pretty quickly, and scale if our projections are off, say, for commercial supply at any point. But we're very confident that we can do this again up to two years of commercialization. Got it. Any questions from the audience? Do we have a mic? Oh, yeah, you can speak. I can hear you. Okay. Do you see any CD22 antigen loss or epitope drift as you see in CD19 and in the escape mechanism in the monotherapy? Is that the reason why you're switching to the triple targeting? Yeah, so it's a really good question, and theoretically, it'd be a reason to address the multiple antigens through a trispecific like we are. We're capturing that data. We haven't released any data, and that's something that we've got a really strong translational medicine group, and so we're capturing those data, and it's a question we have as well, and we look forward to learning more and sharing as we do have data. And maybe just switching gear to CRG-023. Now your IND is cleared by the FDA, and it seems like your Phase 1 is gearing toward third line plus LBCL and including some CAR T naive experience, right? So how should we think about just a development path compared to what we have seen with CRG-022? I mean, CRG-022, you don't have the CAR T naive dataset because it was purely run in Stanford, right? So how should we think about the development path for CRG-023, and where does that fit into the big picture? Yeah, well, I'll start with the big picture. I think the big picture is we are pretty passionate and focused on doing what's best for patients. Having two shots on goal to help as many patients as possible is fantastic. And of course, with CRG-023, we have that potential to even go more broadly in different B cell malignancies because we're targeting three different antigens. So I think the fit, the big picture fit is a really good one for patients, and we see room for patients to benefit from both. And then keep in mind that CRG-022 is out in front of others with a potentially pivotal Phase 2 study and out in front of CRG-023 as well. So we're just committed to getting potentially life-saving therapy to patients with high unmet needs in hematology as quickly as possible at CARGO. So that's the big picture. In terms of the development path, we do have a different opportunity with CRG-023 because we are conducting the Phase 1 study. And so we'll show that proof of concept with safety and efficacy in that study with, you need to start with a more advanced patient population, obviously with FDA, in third-line+ relapsed/refractory large B-cell lymphoma, but inclusive of CAR-naive patients. So we can get that proof of concept there as well, and then move more quickly into earlier lines, and again, possibly to other indications. With firi-cel, just to make this point in case it's not clear, Stanford conducted the Phase 1 study. We are right now demonstrating clinical comparability to Stanford, right? So we achieved analytical comparability before we started the Phase 1. That was a major achievement for the company. And now we're into that next phase. So that's why the development paths are a bit different. And maybe just on your allogeneic, the new data on the allogeneic side, how should we think about that piece, right? Because now we have firi-cel top line coming up very soon. 023 is going into clinic relatively soon. And also you also have allogeneic also kind of running in the background too. So I guess from a data catalyst standpoint, what should we expect from the allogeneic side? And then should we think of the allogeneic platform more of your strategy as a life cycle management for firi-cel and 023? And just how do you think about this piece that kind of envelopes the whole portfolio? How do I think about this piece? There's sort of a beautiful interconnectedness potentially between these programs, right, that can benefit patients pretty significantly. So I'd say that's one. So in terms of what it means for what we're doing at CARGO, there's absolute synergy that I see. And our goal with allo is to just get to proof of concept as quickly as possible. And that is the goal for that program. So there's sort of a CARGO opportunity, but there's also an opportunity for the allogeneic solution, I'd say more broadly. And our commitment there is just to see what we can do to develop that as fast as possible for patient benefit. I think the first part of your question I might need a reminder on. I guess just it's more just about how that fits into, I guess you have answered that, right? How does that kind of build on top of what you already have for firi-cel and also CRG-023? And I guess more importantly, it's just, do you see this as a way to attract partnerships? How do you think about that piece as well? Sure. I mean, I think I've been pretty consistent in just pointing out whenever I get asked about potential partnerships that we've brought together a team with leadership capabilities from discovery design all the way through commercialization so we can build a fully integrated company. And actually doing that is pending results with firi-cel in the first half of this year. But we have the leadership capabilities and experience and know-how and passion to do that. At the same time, we know in this industry that you can do more in partnerships. And so our door is open to really explore what can we do to get potentially life-saving therapies to patients, more patients broadly, more quickly. At CARGO, based on our stage right now, for example, we're focused in the U.S. with firi-cel, and partners could help us get to other parts of the world more quickly. I'd say with CRG-023, there's possibilities that we could go broader more quickly, whether it's geography or other indications. So there's potential to open the door and explore these things. And I'd say the same is true potentially for allo. Again, our allo strategy is fastest proof of concept. Great. Are there any questions from the audience? All right. Well, thank you so much, Gina. It's really good to have you, and looking forward to the data that's upcoming in the first half. So are we. Thanks so much, Brian. Always good to talk to you. Thanks for your time. Thank you.