Hi, everyone. Thanks for joining OpCo's virtual conference today. We're here with Steven Kelly, President and CEO of Carisma Therapeutics. Steven, I'll hand it over to you. Great. Thanks, Tracy. It's our pleasure to be here and happy to walk through an overview on Carisma Therapeutics. Many of you may know of us as the company that pioneered the CAR-macrophage approach in oncology. We continue to develop our deep understanding of macrophage biology, and it really started to hone in on a pipeline that leverages the specific mechanisms of macrophages. Now, as we go forward, I will make some forward-looking statements, but specifically, as we look at macrophage function and how we can apply that to therapeutic outcomes, we're going to look at three different ways to do this. The first is looking at efferocytosis. Normal function for macrophages, everyone has ongoing apoptotic cells that are eaten by macrophages, and it's a constant turnover. We've identified a defect in liver fibrosis where there's a loss of efferocytosis, the ability to clear those apoptotic hepatocytes. We have found a pathway that we've identified. It's called TIM4, and I'll get into it in just a moment, but restoring efferocytosis has a net effect of eliminating fibrosis. We are really excited about this as a growth opportunity for Carisma. In addition to efferocytosis, we have targeted phagocytosis and immune activation. This is the strategy that we've been employing for some time now, where we're looking at cancer cell depletion and driving a long-term adaptive immunity. This is a CAR-based approach or a CAR-monocyte approach, and the applications initially are in oncology. We can also take the same idea, a CAR-based approach, and look at immunosuppression. If you think about taking the ability of getting a macrophage into a specific tissue and using its normal function of reducing inflammation, we can apply that to autoimmune disease. What we're trying to do is harness the power of macrophages, various macrophage functions, and drive a therapeutic outcome in a variety of diseases. Now, historically, we have spent quite a bit of time looking at an ex vivo autologous CAR-macrophage approach, where we would harvest a patient's cells, we would engineer those cells, we would cryopreserve them, and put them back in. As all of you know, this is a very complex process, high cost of goods, that sort of thing. Increasingly, as we go through further development, we're looking at a strategy where we can reprogram macrophages in vivo using an LNP approach to target those myeloid cells and mRNA to express the factors that we're interested in. We've been doing this for the last three years in our partnership with Moderna in our oncology approach. We'll talk a little bit about that. As we go forward in the future, we think that more and more we will start to drive towards an in vivo macrophage reprogramming versus an autologous approach. In that way, we can have an off-the-shelf approach that has a lower cost of goods and certainly decreased complexity. Given our functions and given our approaches, I'm going to talk about the pipeline and then dive deep into a couple of them. First, we have CT2401. This is our liver fibrosis program. It's an in vivo strategy where we're restoring TIM4. TIM4 is the ability to recognize apoptotic hepatocytes. We will announce a development candidate for this program this quarter, and our goal is to have a regulatory submission in the first half of 2026. Outside of fibrosis, we're still working in oncology. Our lead program here would be CT1119. It's a mesothelin-targeted CAR-monocyte. It's an autologous approach, but we're excited about this for a number of reasons. First, it incorporates a next-generation CAR. Secondly, we incorporate SIRPα knockdown so we can eliminate the don't-eat-me signal and so interrupt that don't eat me signal. We're going to do repeat dosing, and we're going to combine with a T-cell checkpoint inhibitor. Now, all that's great. It's going to give us the best experiment that we can do for autologous CAR-M in oncology. We're even more excited. We have found a pathway where we can develop this in a very capital-efficient manner. We found an investigator in China, a manufacturer in China, and an institution that has a high volume of patients. For a very modest investment of $3 million, we're going to be able to go over there, initiate a study in April, and have 12 patients of data by the end of the year. We're very excited about this program. Again, we think it's one of the best experiments we could do for autologous CAR-m in oncology. Beyond this program, of course, we have our partnership with Moderna, where we have up to 12 targets that we're developing with them. The first of those is GPC3 for hepatocellular carcinoma. This is an in vivo approach where we're using their LNP and mRNA technology to engineer or reprogram monocytes and macrophages in vivo. The next milestone for this program will be an IND filing, and hopefully it would occur this year. After that, we've handed off to Moderna, and we've turned our attention to the next targets. There are four nominated targets in oncology, and we're developing one of those. Our goal would be to have a lead nomination and a development candidate for the next of the targets in the collaboration. We'll continue to hand those off and rinse and repeat as we go forward. The last area that I'll touch on is, as I said, the function of decreasing inflammation has applications in autoimmunity. This is a very different approach from the B-cell depletion strategies for the CD19 CAR-T developers. In this case, what we, again, want to do is deliver CAR-M to a specific tissue and, upon engagement, start to produce factors that decrease inflammation. We're very early in this process, a proof of concept stage at this point, but we're excited about continuing to develop this approach as well. Now, let's talk about our lead program in liver fibrosis. CT2401 is an in vivo macrophage that's engineered to address what we think is one of the fundamental challenges in liver fibrosis or one of the fundamental problems. First, on the disease itself, obviously, advanced MASH and cirrhosis is a major unmet medical need. In the U.S. alone, there will be 8 million patients that have advanced fibrosis or cirrhosis. Currently, there's only one approved therapy. It's resmetirom from Madrigal. While it has very good outcomes in steatosis or reducing the fat in the liver, it's a modest benefit in antifibrotic effects. Beyond that, we have the GLP-1s. Similarly, they have an effect in steatosis, a very modest effect in fibrosis. More recently, the FGF21 agonists, there were some data that was presented recently that looks like, again, a modest effect after two years of therapy in about 20% of patients after a placebo adjustment. There is a definite unmet medical need, and this area is expected to grow. We are expecting to be a very significant patient population and a significant unmet medical need. Now, when we look at MASH and when we look at liver fibrosis, we were able to identify a key pathway. It is a pathway called TIM4. What this is, is an efferocytosis receptor that appears to be lost in MASH. Kupffer cells, or the liver macrophages, express TIM4, and TIM4 has the ability to bind to phosphatidylserine, which is represented on apoptotic hepatocytes. Now, when that is lost, you no longer have the ability to remove those hepatocytes. They start to accumulate. They start to drive hepatic cell activation. They drive collagen formation and really lead to the liver fibrosis. It is a key pathway that is dysregulated in MASH. Now, on the right-hand side of the panel here, you can see that comparing normal patients with MASH patients, you see that loss of TIM4. Then similarly, if you look in the graphs down below, in healthy patients versus MASH patients, you see a loss of efferocytosis and an accumulation of apoptotic hepatocytes. This is a unique pathway that seems to be the causative factor for fibrosis to occur in the liver. Now, we went further and took a look at a couple of data sets to see if TIM4 gene expression is lost. These two on the left-hand side, there are two examples where we see the gene for TIM4, TIMD4, is lost in MASH patients in two distinct patient populations. It's not just that one study, but we have others to support this. In our models, we look at mirroring MASH models. It's a CDAA-HFD model where you see, again, the loss of TIM4 in the MASH mice. We think this is a central node, and we want to see if we can approach this in a therapeutic capacity. What we did is we took a cell therapy approach where we had macrophages that expressed TIM4 in a single administration in mice with a CDAA-HFD MASH diet to see if we could restore efferocytosis. In the graph here in the middle, you see PBS control macrophages and TIM4 macrophages. You can see that we were able to restore efferocytosis, about a 47% increase in efferocytosis. Similarly, when we look at what's happening on fibrosis, we saw a 49% decrease in fibrosis. The TIM4 macrophages significantly reduced hepatic collagen and repaired efferocytosis and have a positive outcome. We are really excited, thought that's fantastic. This is mirroring models with mirroring macrophages and mirroring TIM4. We wanted to do the same thing, and we looked at human macrophages with human TIM4, and we saw the same thing occur. Human TIM4 transfer resolved a number of different factors. We look at hepatic stellate cell activation, and the columns here are non-MASH mice, MASH treated with saline, MASH with untransduced macrophages, and MASH with TIM4 macrophages. Stellate cell activation goes down, inflammation goes down, collagen goes down, and fibrosis goes down. It's not just the mirroring models, but also looking at human cells and human TIM4. We think we're onto something. We took a deeper look and said, "Okay, if we're restoring TIM4 function, is this going to be a positive outcome? How often will we have to do this?" It turns out TIM4 efferocytosis initiates a positive feedback loop. You see further expression of the TIMD4, so efferocytosis receptors MERTK as well. We also saw an increase in key anti-inflammatory genes, IL-10 and PD-L1. There's a self-perpetuating feedback loop that continues with efferocytosis. This is not to say that we wouldn't have to keep on dosing, but it also is able to reprogram existing cells in the liver. We took one further look looking at RNA-seq, and we were able to see that a number of different pathways are upregulated after treatment with TIM4 macrophages. Similarly, some are decreased. On the left-hand side are pathways that are decreased. Without reading through all of them, we're seeing TGF-beta signaling, fibroblast activation signaling, extracellular matrix production, inflammation. All of them go down. These are all central to fibrosis pathogenesis. On the other side, genes that are increased are around lipid metabolism, protein metabolism, fatty acid metabolism, aerobic respiration. These are all metabolic pathways that are dysregulated in MASH. We're seeing this TIM4 replacement have a significant outcome, not just in fibrosis itself, but the entire remodeling of the function of those macrophages. Our goal is to move this into an mRNA LNP approach. We used a tool compound, MC3. It's an LNP from Onpattro. Here we added TIM4, and we dosed mice in three doses. We were able to see a reduction in collagen in the TIM4 mice relative to vehicle. We also saw the—we were able to transfect the mice in a dose-dependent fashion, and we saw increased efferocytosis over time. Our goal is to have a proprietary LNP, not that tool compound. We have identified an LNP that is optimized for liver fibrosis. We look here and compare vehicle to MC3 or the tool compound and a proprietary LNP. We are able to see a very good transfection of Kupffer cells. Those are the liver macrophages. We see that both in liver and in blood. Importantly, we also see that even in fibrotic liver, we have high levels of transfection. Looking at MC3 in healthy versus fibrotic tissue is a significant reduction, but the proprietary LNP is high and remains high over time. We think that we have an LNP that's going to work well. Our goal, of course, is to get this into the clinic as quickly as possible. We just presented a preclinical proof of concept at AASLD. We're going to finalize a license agreement for the LNP and mRNA manufacturing, and we'll initiate IND-enabling work this quarter. Our goal is to have a regulatory submission and initiation of a phase one study in 2026. We're really excited about this for liver fibrosis. We don't think it just ends there. It appears that macrophage efferocytosis dysregulation occurs in a number of different diseases. Pulmonary fibrosis is an area that we're very interested in looking at. Atherosclerosis is as well. You can continue to look beyond that, neurodegenerative disease and autoimmune disease. We think that efferocytosis and disruptions in efferocytosis have a tremendous role to play in the formation of fibrosis, and restoring efferocytosis should help us resolve a number of different diseases. That is the efferocytosis story. As I said, we continue with 1119. This is our anti-mesothelin CAR-monocyte. Here, we learned a lot with the HER2 program. A lot of you are probably familiar with our HER2 program. We saw a tremendous amount of activity, TME remodeling, reductions in ctDNA, a marker of reductions in the tumor itself. We were able to manufacture a whole host of things. What we learned is that we need to switch to monocytes to make a higher number of cells, approaching 10 billion cells. We need to redose. Pharmacokinetics work suggests every three weeks we should redose. Our goal is to move into the clinic rapidly with CT1119. Again, it incorporates a next-generation CAR. It incorporates anti-SIRP alpha knockdown. We will be dosing on a repeat dosing every three weeks or so. We think we'll have about 15 weeks of on therapy, and we'll combine with an anti-PD-1. This is a very cost-effective way for us to rapidly develop an anti-mesothelin CAR-monocyte in China, and we'll have results at the end of this year. I'm just going to jump forward. Lastly, we'll talk about the Moderna partnership with in vivo CAR-M. This is something that, again, we took our ability to reprogram and understand the mechanisms of macrophages. Moderna is the world's leader in mRNA and LNP technology. Together, we are able to develop a robust platform for oncology and autoimmune disease. This gives us a product that's off the shelf, has the ability to redose, and we have been able to show significant activity in preclinical work. The partnership has been in place for the last three years. Upon success, we are $3 billion in milestones and a good royalty. We're excited about the progress that we've made so far. The first program, it targets GPC3. It's a validated target in hepatocellular carcinoma. A very high unmet medical need is the second leading cause of cancer deaths worldwide. We know that GPC3 is a cell surface antigen. It's overexpressed in 70%-80% of hepatocellular carcinoma. We've been able to show activity. Our goal was to move to a development candidate. We reached that phase. We have an in vivo CAR-M that uses the mRNA LNP approach. We have a novel next-generation CAR targeting GPC3. It shows data that we were able to clear a lot of the tumors and metastatic tumor nodules. You can see in the mice here, this is with our anti-GPC3 CAR compared to control mRNA LNP and vehicle. You see a much better outcome. If you look at the tumor itself and histology, we are able to eliminate all of the GPC3 positive tumor nodules. We are excited about this. It is moving forward. We hope to get into an IND and into the clinic this year. As I said, we continue to work on the additional nominated targets. We have this modest work ongoing in autoimmune disease. Very exciting partnership, very exciting that we'll be able to move this into the clinic and have an in vivo CAR-M in oncology. Now, just briefly, in terms of our milestones, we have along those three lines that we talked about, just to recap, with the liver fibrosis program, our next goal is to nominate a development candidate this quarter. We'll be working on our IND-enabling work by the end of the year. Our goal is a regulatory submission, likely going to Australia here, but a regulatory submission in the first half of 2026. In our oncology program, our mesothelin targeted program, CT1119, it's a CAR-monocyte. Our plan is to initiate a phase one study in the first half of this year. We're hoping it'll be early Q2. This would drive us to fourth quarter of this year, initial phase one data. With our partnership with Moderna, our goal is to have an IND application for the GPC3 program. As we look at the future nominated targets, a lead candidate and development candidate for the next target. Again, we continue as we go through each one of those. Autoimmune's early. Our goal is to have a proof of concept in this area. We're hoping to demonstrate that this year as well. That is the story of Carisma. We have multiple programs that we're pursuing, many milestones that we're going to be hitting across each of those programs, whether it's fibrosis, which again is a really unique and untapped potential that starts with liver fibrosis and goes to other fibrotic disease. We have oncology with our own autologous program and our partnered in vivo CAR-M programs and early work in autoimmune. I'll pause there and happy to take questions if that makes sense. Thanks, Steven. I think we have just a couple of questions in the queue. The first one is, within autoimmune, how are you thinking about potential indications? Yeah. No, it's a good question. I think that the cell therapy approaches that have been pursued are a B cell depletion strategy. We use the CD19 CAR-T or CAR-NK programs that do the same thing that they were doing in oncology and for heme malignancies, in this case, deplete B cells. Our approach is different. While we think it's feasible to do the same sort of thing, we can eliminate B cells using a strategy. Our goal here is to localize to tissue in—we're a little nonspecific because we have sort of confidential issues with the partnership. We could target a tissue, pick any autoimmune disease. As long as we can get the CAR to that tissue and identify a particular antigen target within there, it's not going to lead to phagocytosis. That's not our objective. What our goal is to do is to start to change the environment and produce a number of factors that reduce the inflammation in the space. We have done a lot of work with either expressing certain factors, immunosuppressive factors, or using switch receptors to do that. The idea is to have very good tissue specificity and reduce inflammation. Thank you. The next question is, are you looking to partner 1119 and 2401, or how are you thinking about near-term business development priorities? Yeah. We have been doing partnerships for the life of Carisma. We have worked with Novartis on a big manufacturing program. We obviously have the Moderna partnership, which has been fantastic for us. We look at these as assets. The goal for us is to accelerate development. We think the science is really game-changing. We need capital to develop them. If we can get both capital and the means to accelerate them, whether it is deep expertise in a particular field or other support work, we are absolutely going to do that. CT2401 is wholly owned for us. We would welcome a partnership if it made sense, both economically and functionally. Similarly, CT1119 is wholly owned by us. While we will be doing the work initially in China, I think with success, we will bring it back to the U.S., and it would be available for partnering along the way as well. We are open to those partnerships. We are open to autoimmune. Right now, the field of oncology in vivo is partnered with Moderna. Autoimmune, we have two nominated targets, but we can use both cell therapy and in vivo strategies in autoimmune disease. Partnerships are an important part of our capital formation strategy. Thank you. I think that brings us to the end of our Q&A. Thank you, Steven, and thanks, everyone, for joining today. Thanks, Tracy.