Today, as Daniel says, I will give you a good overview of Carisma, what we're working on, and sort of the next milestones. I will be making forward-looking statements throughout the presentation. You can read this on our website, so Carisma is founded on the idea that we can engineer macrophages to have therapeutic effects. We have a deep understanding of macrophage biology. We have a whole suite of tools to engineer those cells for our purposes. Our first application will be using these cells in oncology, is what we started on, but we also learned over the years that we can now direct these cells to do other things, including work in liver fibrosis, and as you may have seen yesterday, work in autoimmune disease.
If you take a snapshot of the company today, we have four basic areas that we're pursuing. We have Ex Vivo oncology, and the sort of bellwether there is our work with the HER2-directed CAR-M program. The second area that we're pursuing is In Vivo CAR-M for oncology. This is a partnership that we put in place with Moderna about two and a half years ago, and the leader in that space is a GPC3-targeted CAR-M. The third area that we're developing is In Vivo CAR-M for autoimmune disease. Again, we just announced this as an expansion of the collaboration with Moderna yesterday. We have two targets that we're pursuing in autoimmune disease. And lastly, liver fibrosis. This is an area that we can direct macrophages, engineered macrophages, to have a therapeutic effect. So four basic areas.
If you look at sort of the pipeline and how that lays out, our lead program, CT-0525, is in a phase I study. I'll talk more about that in just a moment. The next milestone out of that program, though, is coming up. It's in the fourth quarter of this year. We'll be able to report data on the early phase I portion of the study. The next program, that is near term, is our GPC3-targeted CAR-M. The next milestone there will be coming up in the first half of next year, and that's an IND filing and moving that program into the clinic. We have the next program to highlight here is our 1119 program. That's currently at a point that we can drive into preclinical development when we want or into IND-enabling work when we want to.
It's right now paused at this point. The next milestone, of course, would be an IND there. In addition, we have four other targets partnered with Moderna in oncology. The next step there would be to nominate one of those for moving it forward. Liver fibrosis is an area of growth opportunity that we'll talk more about. We are well on our way to developing or nominating a development candidate, and that will occur in the first quarter of next year. And lastly, like I said, autoimmune disease is new. We don't really talk too much. Moderna is tight-lipped and likes us to be tight-lipped on exactly the milestones and targets and things like that. But the next step there would be to nominate a target.
I think it's important to note, if you look at this pipeline chart, in the places where it says Moderna is partnered, those are fully funded. So right now, if you think about the company, we're funding CT-0525, and we're funding liver fibrosis on our own. The rest of the areas are funded by Moderna in our collaboration agreement. The other thing to note is that we are available to partner these other targets as well. Now, turning to our first program, the HER2 program. This is where we started. We started with the HER2 targeted CAR macrophage. We've learned a lot out of that program, and we are transitioning and have transitioned to a CAR monocyte, and I'll explain why. With the HER2 program, when we started, we looked at a macrophage.
The idea is that our macrophage approach is going to do several things. One, it's going to be able to localize into the tumor. It's able to kill directly through phagocytosis. They're going to be able to remodel the tumor microenvironment, turning cold environments into hot environments. And they're going to be able to drive an adaptive immune response through T cell recruitment and antigen presentation. We've asked the macrophages to do all of that. To get there, though, they have to travel through peripheral blood, they have to extravasate, they have to penetrate tissue and get into the tumor. And what we've learned along the way is that's a pretty high hurdle. And so just to summarize the learnings from CT-0508, one, we learned that it's safe. We have low levels of CRS.
We have no ICANS or neurotoxicity has been observed. No on-target, off-tumor toxicity. It's a very clean safety profile, and we believe this gives us a wide therapeutic window for the CAR-M approach. We also learned that we can manufacture these cells reproducibly at reasonably high volume with good purity, good CAR expression, and M1 polarization. That was really important. Never been done before. In terms of the therapeutic outcomes, we did see tumor localization. We did see remodeling of the TME. We did see anti-tumor effect, including stable disease in a number of patients, and we saw evidence of an adaptive immune response. Now, one of the things we saw, though, is that we're probably getting an insufficient number of cells to the tumor, and they're probably not sticking around long.
Using ctDNA as a biomarker, you can see in six out of the eight patients here that there is a reduction in tumor burden and then a four-week lag and then a recurrence. This tells us that we're probably not getting. Well, we have a biopsy saying we're not getting enough cells in, but we also see that they're not sticking around long enough. We have to address our persistence with our cells. The next, I'll skip that. So the next thing we saw is that T cell exhaustion was limiting that last element, that adaptive immune response. So if you looked at our patient population, there are six lines of prior therapy on average, up to eleven lines of prior therapy.
If you look at their exhaustion markers, T cell exhaustion markers like LAG-3, PD-1, TIGIT, they're definitely higher and become exacerbated when you treat with CAR-M. In terms of differentiating how important is that, we broke it down to high levels of exhaustion markers and lower level of exhaustion markers, and looked at progressive disease or stable disease. In blue are the progressors, high levels of exhaustion markers. You're more likely to have a better clinical outcome with low levels in orange. So these are all the stable disease patients. So we know T cell exhaustion is an issue. So I'm gonna skip. We did do a study with anti-PD-1, with pembrolizumab, and we did see that there is some synergy.
We were able to show an increase in T cell clonality when we added pembrolizumab to overcome that T cell exhaustion. We saw an increased effector memory cells. We saw an increased number of CD8 positive T cells, and we also saw an elevation of PD-L1, suggesting that you're going to be more responsive. This is a patient population that doesn't respond to PD-1. They're gonna be more responsive. So we did see some synergy there. Now, we have three things to overcome. We need to overcome the cell number, we need to overcome persistence, we need to overcome T cell exhaustion. The cell number and persistence is going to be addressed through our CAR monocyte program. Monocytes, again, are the cells that travel through peripheral blood before they extravasate and get, and come into tissue.
They will differentiate into macrophages once they're in the tumor. And so think of this as a pro-drug approach, where we start with a cell, and then it differentiates and becomes the cell that we really want it to be. What we learned when we started making monocytes are that there are several biologic advantages as well. So, we're using the same CAR construct, same polarization, et cetera. But we learned we can make five times the number of cells, so 10 billion monocytes versus about 1.6 billion macrophages. The second thing we learned is that there's a different chemokine profile on monocytes. They're high expressers of CCR2. Tumors produce CCL2 to recruit in myeloid cells, and so our monocytes actually have a higher level of CCL2 or CCR2, and they're able to be brought into the tumor.
We see a forty-fold improvement in localization of monocytes into that tumor, and again, they turn into macrophages. So we're getting more cells in and they're into the body, and more of them are trafficking. Lastly, on the persistence issue, CAR monocyte, the CAR monocyte product, CT-0 525, sticks around about ten times longer than CT-0 508. So if you think about five times the number of cells, forty-fold better trafficking, ten-fold better persistent, there's a two thousand fold improvement of therapeutic pressure against the tumor than we were able to see with a CAR macrophage. So we're really excited about this product. We've moved it into the clinic.
We're doing a dose escalation, so two cohorts, one at three billion cells, which is about 50% more than we saw with 0508, and then at 10 billion cells, so five times the level we saw with 0508. So, this data will report out in the fourth quarter. We'll have safety, tolerability, manufacturing, feasibility of monocytes. We'll have that cell number in tumor, persistence of those cells. We should be able to look at a objective response readouts, and we should be able to look at some of the other corollaries, ctDNA, et cetera. Our goal is to have that data for you in the fourth quarter. But where do we go after that? We are obviously in this dose escalation phase.
We believe we can move into two separate areas that we wanna explore. One is repeat dosing. We have 10 million, 10 billion cells to work with. So we're evaluating whether we should use a bolus infusion or, for example, five cycles of 2 billion cells to maintain those monocytes over a 15-week period. In addition, we wanna look at the adding pembrolizumab to a combination approach, and we may do both at the same time. So we're still working through what that third cohort looks like, but the goal is to have sustained pressure of monocytes against the tumor and overcome T cell exhaustion with pembrolizumab. So, look for data at the end of this year. The cohort three data will be in 2025. Now, moving on from our HER2 program.
In Vivo CAR-M, first in oncology, is again this is a program we put in place with Moderna about two and a half years ago. Twelve oncology targets, we're able to use their LNP and mRNA technology to deliver a mRNA that encodes for our CAR. So same reprogramming of the cells, but in an off-the-shelf fashion that directly delivers the mRNA to myeloid cells. Again, this was put in place about two and a half years ago, $80 million up front, fully funded by Moderna. So beyond that $80 million up front, every quarter, we receive a check from Moderna to fund the work that we're doing. On the back end, there's a good royalty, and there's also about $3 billion in milestones. Now, as a proof of concept, we presented this at SITC last year.
This is a model system where we used HER2, not an antigen in the collaboration, but we had a pancreatic HER2 positive tumor where we redosed or repeat dosed an LNP encoding for our CAR. And you can see on the bottom, vehicle, no effect, control mRNA, you see pretty significant tumor growth. CAR mRNA, we're seeing complete control. We also were able to see no adverse safety events. And it's important to note that the LNP that we're using has been repeat dosed in humans before. So we're confident that we can do that as we move forward. The first development candidate nominated was GPC3, Glypican-3. It's a validated target in hepatocellular carcinoma.
It's a large unmet medical need in the U.S., about forty thousand patients, second largest cancer source of cancer death worldwide. So it's a really important antigen target that's been validated and treated in the past with antibodies, and there are CAR T approaches as well. The steps here are to move forward and get it into the clinic as soon as possible. We nominated a few weeks ago. It hands off to Moderna, and they take the ball and run with it. And they have more people working on this now than employees of Carisma. So the rest of the preclinical work, the manufacturing work, the clinical work, and the goal is to get this into the clinic as quickly as possible. On our hands, we then turn and look at other antigen targets.
Again, there were four antigen targets in oncology. We turn our attention to those and move those forward to have a lead as well. As I said at the outset, we just announced an expansion of the collaboration to look at autoimmune disease. We can use the same idea of using a macrophage. A macrophage is an orchestrator of the immune response. We can dampen the immune response. A macrophage will produce cytokines. We can lower inflammation. So there's a lot of things that we can do to address some of the autoreactive B cells and T cells in autoimmune disease. We're not talking about what those targets are, but it's a pretty exciting approach that is, it's validated targets, and we'll talk more as we progress in the future.
Lastly, I wanna talk about our last area, which is fibrosis. Fibrosis is an interesting disease. But of course, there's a lot of interest in fibrosis, especially as it relates to MASH. A recent approval of Madrigal's drug, resmetirom, was approved. A lot of effects looking at steatosis, not a tremendous outcome so far in fibrosis. Now, we know that macrophages are involved in fibrosis in liver. Kupffer cells can keep fibrosis at bay, but there is a loss of Kupffer cell activity and a loss of macrophages initially that are repopulated by bone marrow-derived macrophages.
We also can look at the literature and see that there is a population of macrophages that are Stuart Forbes in Scotland did, where he harvested, purified the macrophages, and administered them, so unengineered macrophages, and it kept the fibrosis at bay, not improving, but keeping it from moving forward. We think we can do one better. We think that we can engineer these cells, leverage the ability, the restorative properties of macrophages in liver fibrosis, but also add some engineering. So we've made a macrophage that also. So we encoded it to express relaxin, an anti-fibrotic, and IL-10, an anti-inflammatory. The idea here is to administer the macrophages. They become liver resident.
It cleans up all the dead cells and the debris, and then, as a micropharmacy, that produces these two factors in the liver. We put this to the test, first in a toxin model, the carbon tetrachloride, a pretty standard model in liver fibrosis. In this case, it's about a six-week model. We administer one dose of macrophages, and you can see in the bar graph here, comparing to unengineered macrophages in our relaxin IL-10 construct. Unengineered macrophages have a pretty good effect, there's no question. Engineered macrophages completely restore function, liver function, and eliminate fibrosis. And you can see on the far side. Oh, this is a pointer. Does this work? Yeah. On the far side, the histology that it's all fibrosis is eliminated.
That's pretty good for a first step. We took it one step further, however, and said: What about in a MASH model, where we're looking at a high-fat diet? Six months in a high-fat diet for the mice, and then made it harder by adding a liver toxin as well. So this is a pretty high bar for the approach. Again, we treated with vehicle control macrophages or engineered macrophages, and we were able to see a pretty good response. So about 25% improvement with unengineered macrophages and around 45% improvement with engineered macrophages. Just as context, if you took this model and used something like resmetirom, I think they're gonna perform it at the 12% to 15% level. So we're having a pretty robust effect on fibrosis in late-stage disease.
Now, you will note steatosis is still a factor, but we're limiting the fibrosis here. We're excited about this program. Our next steps are to finalize the constructs. We do have other variables that we're looking at, variable payloads, and so we're going to finalize that in the next several months. We're also going to finalize the modality. So these models were autologous, but we'll be looking at In Vivo. So it's an important area that we can build our own In Vivo capabilities. And we'll look at allo as a backup in that area as well. Our goal is to, by Q1 of next year, to announce the development candidate, including the modality, as we move forward. So those are our main programs.
In terms of the company itself, we're at with $40 million in cash, takes us into Q3. Just to sort of look at the milestones as you reiterate what I've said. With our HER2 program, phase I data, dose escalation by the end of the year. With the GPC3 program and IND, first half of next year. With liver fibrosis, a development candidate in Q1. So a lot going on at the company, and we're grateful to have a partner like Moderna funding a lot of our programs, and we're grateful to be in the position to have these milestones as we move forward. So I'll pause there and happy to take any questions.