 All right, hi, let's get started. I guess I know most of you. My name's Emerson Perrin and I've been here for a while. And many of you have heard me present about cell therapy in the past. And as a global perspective on this, we injected the first human with cells back in 2001 in Brazil. And so this is more in 2021. But it's a relatively young field. 20 years is nothing in the development of cardiovascular medicines. Aspirin's been around for more than 100 years. You still don't know exactly how it works. It took about 30, 40 years to get ACE inhibitors into ARBs into things that we use commonly now. So having something that is a live functioning entity that interacts with this environment is very different than a simple molecule. So that adds further complexity to it as well. Further, the cells that I'm going to be talking about today, we first injected in 2006 in Newcastle, Australia. So that's about 15 years we've been working with this cell. And as with anything, as you progress and you do trials and you learn things and you take steps, this is the latest step that we've taken. And for those of you that had followed along, you'll see that we have some new and exciting data and actually looks like we're getting somewhere. As with anything, whenever you have some kind of a new treatment, there's a lot of hype and hyper over inflated sort of expectations about what you do. And I remember back in the early 2000s, it's like, oh my God, cell therapy is fantastic and it cured the world. And it probably will. And everybody in this room has made a two stem cell. So there's no question that it works. The question is how do you get it to work? And so then that initial incredible expectation kind of goes away because nothing happens for quite a while because yeah, it's really cool, but you kind of need to figure things out. And then over the subsequent years, research is done. A lot of things are done. Things are better understood. And over time, you get to an understanding through research to the point that you actually then start catching up to that initial hype that you had. So this is kind of where we're getting here. So this trial is called a DreamHF trial. And I was the co-PI of the trial. And we let it, I see all my research coordinators here from Texas Heart is pretty much the leader of this trial. And so it's a great pleasure to now after six years, I'll show you the timeline after six years of work to have been able to present this. Let's see. I'm not advanced. Let's see. Oh, there we go. OK. This is actually over. I over disclosed. It's basically because I'm the PI. So DreamHF is multi-center, randomized, double-blinded. We'll talk about how this is done because it's quite involved, the sham control. And it's an event-driven trial, meaning it's not a trial that you have a predetermined end. You need to reach a certain amount of clinical events for the trial to be over because those events are calculated and then reach a point where either you have significance or not of what you're doing. The trial was actually quite an interesting history. It was initially sponsored by a company called Cephalon. And then Cephalon got acquired by Teva, who's a generic drug maker, who wanted nothing to do with a cell therapy trial that we had just written and gotten ready to start. And subsequently, then, Mesoblast, who is the company that has developed this cell and has a proprietary way of getting these cells, then took over the financials. And it was pretty interesting because we really had to do a lot of work to get the trial down to a smaller size from a financial standpoint. Originally, it was written as an 1,800 patient trial. Big pharma, 7,000, 8,000 patients is nothing. Well, you try to do something this involved. It's not like give everybody a pill every day. This is a pretty significant procedure with a lot of things, as you'll see. So we, through changing endpoints and looking at things, we're able to get the trial more compact and down to a goal of around 600 patients is where we ended up. So there is a clinical endpoints committee that adjudicated every single meaningful clinical endpoints such as death and strokes and heart attacks and all these events that happened to the patients over time, and these events are delineated in a document. And there was a data monitoring safety committee that was headed by Dr. Roulou, who's the head of the Montreal Heart Institute. Really great group of guys that sort of monitored this study over time and made sure that we weren't causing any harm. And also in 2017, we had a futility analysis to make sure we weren't spinning our wheels and there was no chance of this being positive, which we passed, luckily. So this study was done across 51 sites in the U.S. and Canada. We're one of the top enrollers and you can see, here, let's see if I can get this error. So there's a heart failure team and there's an interventional team. And so because this is a kind of a phase three trial, it has to be blinded. And you really have to have a firewall to keep it blinded because we're doing procedures on people. So when you're doing a procedure, the guys doing the procedure know exactly what they did. And so we have this structure in which the procedure itself, when the patient came in to get the cells into the heart, that was done by a certain team. And then there was another team that then screened the patient, saw the patient initially, and then after that initial procedure in the hospital, then follow the patient for the duration of the trial. And so there was no communication between the two. I couldn't even go near the cath lab on days in which we had a procedure because I was the blinded part of the heart failure team. So that sort of guarantees that it's a blinded trial. And then a little bit I'll talk about what we did to actually blind the patients that were in the trial. And here's the continuing list of sites. So it's pretty involved and it's quite interesting having gone from doing 60, 80, 120 patient trials to doing a larger trial like this. So let's talk about the cells a little bit. So when we talk about cell therapy, okay? It's not one thing. So it's like cars, there's all different kinds of cells. And so it may be that one cell is really fantastic and another one is terrible and all the shades in between. So mesenchymal precursor cells are a very specific kind of cell. And we get these cells from the bone marrow. So these cells are selected with an antibody. It's an antibody against stro3. And these cells are characterized by having this receptor called stro1. And what they are is they're mesenchymal cells but which are the cells of the stroma of the bone marrow that have the ability to turn into different tissues. So they're true stem cells. And with this marker on it takes it back a step. So this is the cells that are like a generation before. So if the mesenchymal cells are like one in a, you know, 100,000 or whatever cells in the bone marrow, this is like one in a million. So it's a rare cell. And then once you get that cell, which is a very specific kind of cell, then you can stem cells have a property of cell renewals. So it's either grow. So you can grow these cells into cell banks. And so in this trial, for example, we had three different donors. So but we could have just had one. So you can have one donor provide cells for, you know, 1,000 people study. The advantage of this is so as it says here, they're allogenic meaning they're not from, you know, everybody's not getting their own product. That has been a real problem in cell therapy because when you give autologous therapy, especially if you're talking about your own cells, everybody's different. So if you take an 80 year old guy who's a smoker and sedentary diabetic, his stem cells are not that great. If you take an Olympic athlete who's 18 years old and super healthy, his stem cells are awesome. So using allogenic cells enables you to give the same product, that super healthy powerful cell to everybody. Now you can't do this with every kind of cell because not all cells are fly under the radar of the immune system. So these mesenchymal cells do fly under the radar. And that's real important. So if we get, for example, we took a biopsy of the heart and took a cardiac stem cell and multiplied those and gave those, you would just like a heart transplant, boom, you get rejection and you'd react and kill those cells. The mesenchymal cells, we inject them into the heart, they do their thing. They eventually probably go away. We could talk about that later. So there's a actually large animal work and sheep work in both non-eschemic and ischemic cardiomyopathy that show that these cells have, that they're very well studied, have anti-inflammatory and immunomodulatory, pro angiogenesis, anti-apoptotic effects. So they do a lot of good things. And they do these good things in models of large animals that are both ischemic created models and non-eschemic created models. So we performed a trial that got published in 2015, which is the phase two trial that's published in CERC Research that showed some really exciting things and it showed decrease in remodeling, improvement in remodeling of the heart and also less events in the patient that got these cells. And that was very important because it allowed us to negotiate with the FDA to be able to do this trial, the dream HF trial. So let's go over this a little bit. I know it's a kind of a complicated cartoon here but this kind of tells you a lot about the mechanisms because when I show you the data, we're gonna be referring back to what these cells do and it's all gonna make a lot of sense. This trial is beautiful and nothing else, it is extremely consistent in everything we see. I'm showing you parts of it but this is the stuff that a little bit more than what I presented over the weekend. So here we have the heart. Heart failure is something that is basically initiated by innate immunity and adaptive immunity. And there are cellular and non-cellular components but a major component of what makes heart failure, heart failure is that the inflammation that happens with heart failure keeps it going over time. And so you have cells in the heart and one of the main players are macrophages. And there's different, there's kinds of macrophages that this is a little simplified but there's kind of macrophages that come from the bone marrow, there's different kinds but they're the actors that do bad things given their stimulation from the environment and what's causing the heart failure. And so we'll just call these M1s, okay? So this is a simplistic classification into M1, M2, it's a little bit more complicated but basically M1 are pro-inflammatory cells, okay? And they secrete, as you can see here, TNF alpha, IL-1 beta and IL-6, these are three important inflammatory cytokines. And these are responsible for a lot of the bad things that happen. Well, if we then take an NPCs as a picture of the cell, let's say, and we put it in the heart, these cells have receptors for TNF alpha, IL-1 beta and IL-6 amongst other things. And so if you put them in that environment where these cytokines are all there, it's like if you throw somebody a fireman into the middle of a house that's on fire, these receptors, the cells get activated and they understand, oh, this is an inflammatory environment and they do what they're supposed to do which is counter the inflammation. And so then these cells secrete a bunch of different things which is kind of simplified here but they counter that inflammation, okay? And they do it at the local level and as you'll find out, they do it on a systemic level as well. So basically they have an action that polarizes these M1s into M2s which are not inflammatory, they're healing, okay? And instead of secreting all these bad actors here, they secrete things that have a lot of beneficial effects on the smooth muscle, on the endothelium, on blood vessels and on the heart muscles themselves that changes, you know, energetics, metabolism, versus apoptosis does all a lot of things locally at the heart muscle. But if you ever studied atherosclerosis, you know that atherosclerosis and development of plaques and plaque ruptures and heart attacks, that is a immune process. These cells are immune modulatory, meaning they modulate that stuff, mainly through these macrophages, okay? So they have an effect on the heart but they also have an effect on blood vessels. And just as an aside here, to note, it's important that IL-6, there's a soluble portion of IL-6 that leaves the heart and that induces in the liver production of CRP. And what we commonly measure CRPO, somebody's got a high CRP, it's an index of inflammation, you know, and that'll be important later, we'll talk about that. So this is a great, so you think, you look at this and you think, oh man, this is a great way to treat heart failure is to treat inflammation. So there have been, there are three trials of anti-TNF alpha led by Doug Mann, who we all know here. And actually the trials were stopped early for lack of benefit. So there has been a failure so far of therapy that we mainstream treatment to treat inflammation in heart failure. Now, an exception to that is this trial called the Cantos trial that was directed against IL-1 beta, but it wasn't really a trial looking at heart failure, it was a trial looking more at the sclerosis. But there are signals in there that there was some benefit in subsets of people with heart failure. So, okay, so let's talk about this trial. So the main inclusion criteria were that people had to have chronic, and it could be of ischemic or non-eschemic origin, because I told you these cells have been tested in both. And that's a fun thing to discuss later. And everybody was on optimal medical therapy. This trial was performed between 2014 and 19. So not everybody was on SGLT-2 inhibitors, but it was interesting to see in the beginning we had like 2% of people on intresto or 5%, and that went up to 50% towards the end of the trial. So all these patients are on the best possible guideline directed medical therapy. They had to be no option for other things or else you do those other things if somebody needs a standard bypass surgery if they're ischemic. They have to have a ejection fraction of less than 40%. And all of these patients that were either class two or class three, we enriched them for events. This is an event-driven trial. We want to see events. So how do you do that? Well, everybody that got enrolled had to have an admission for heart fader in the nine months prior to randomization or a visit to the ER where they got IV diuretics or IV treatment. Or they had a biomarker, anti-pro-BNT greater than 1,000. So these are things that selected out a population a little bit more likely to have events. Oh, and exclusion were basically we didn't want any acute patients or unstable angina recent heart attacks, things like that. We want a stable chronic heart failure population. Okay, so then how do we give the cells? So you can see on the panel here we took these patients to the cath lab and like I said, we needed to completely have them blinded. So as they go into the cath lab when we do an electrical mechanical map which is this structure is a three dimensional model of the heart that we create by touching the heart on the inside and that we color code for voltage in this case which tells us what's more alive and what's not so we can see scar, we could see good tissue, we could see normal and sort of intermediate tissue. But so to go in and do that we always take a picture of the pumping chamber. And so everybody that went into this trial they went into the cath lab and they got a stick of their growing and we did an LV angio on them. And that it gives you the kind of a hot flash and it gives you a stick in your artery. So the patients and then they're sedated. If they were to get cells, we continued on with the mapping and the whole thing and did actually what we do in terms of injecting these cells Dr. Fishin, Dr. Chang are the guys that did the cell injections here. And if they weren't, if they were a sham control that's why we call it a sham control then after that they sat there and did master piece theater which is basically make believe you're doing an injection and we would have a script and people say, okay, now point number one and the voltage is this injecting did this and so you just went through this theater of and it would take approximately the same time so the patients couldn't tell oh, I was on in there for 10 minutes so I must not gotten the thing. So this is a very well thought out FDA agreed upon kind of thing in which then the patients that went to the cath lab were completely and plus we sedated them heavily. So with all of this, they had no idea they got a stick in their groin they felt some stuff in their heart and they don't know if they got a procedure or not that's very, very important. And it's also, as you know, very important for the us investigators not to know either because there's all kinds of bias if you know what your patient got even if you're trying to be the most the best investigator in the world you will be biased about things because you want your, we're not doing this because we don't think it doesn't work we think it's going to help people so we want to see it work. So for the people then that got randomized to getting cells, we perform this map. So here's the catheter goes back through the aortic valve it touches the heart and here so you create this shell that's color coded. So here, for example, let's say if there was a scar in the apex and then this intermediate and the colors were representing or the visible spectrum of light so it goes from red on the low side to violet on the top side. And so like this purple stuff would be normal tissue this would be intermediate this would be a scar. So you can look at the heart and you can see on a completed map you can see, okay, this guy had an LED in park. Okay, he's got scar here in the front of his heart. And here the black dots you can see where we did the injections. So there's a needle that runs through the catheter after we mapped it we had very specifically decided that we're putting these cells into intermediate voltage, not scar tissue. If you put it into dead tissue the cells are not going to get activated they're not going to see anything. If you put them into normal tissue that's not a good idea either. So this is, we've been doing this for a while and this is how we think it's the best way to proceed. So here you have a finalized map and there are the injections. The idea was to give between 15 and 20 injections and we achieved that in the majority of patients. Actually, here's the slide showing that actually 96% of the patients received the specified 15 to 20 injections. I talked about the duration of the trial. I had a symmetric slide. This wasn't in presentation but you can see here from the first patient visit in March of 2014 all the way to the last patient visit in February of 2020 we had to wait another year because the last patient and when he got treated we needed to be a year to go by before we could start closing down the trial and starting to get ready to look at the data. So it's a six year long trial that was decided to stop when we got a call from the data monitoring safety committee saying, we don't know about it we're just doing the trial, right? We're just doing this. So they're saying, okay you have reached the events number that is we think that you have a meaning for result you can now stop the trial. And I actually fought and I said, come on man let me, it was like December and I wanted to, I said we need to reinforce our end points a little more but they made it stop. Okay, so here is a flow diagram of how the study happened and here you can see a big miss that I won't do this again. So 1167 patients were assessed and screened and you can see here, 565 were randomized. Now there was an issue between, well so of the 565 patients you can see that 537 actually got randomized and treated. So I'm sorry. So these guys between when they entered into the trial there was a month gap between these things. And so patients violated the protocol. Let's say I told you you couldn't have an MI well that patient that got accepted into the trial had a heart attack, boom we can't put them into the trial. So nowadays what we do in every single trial and it's pretty much standard is you randomize usually if it's a procedure trial at the day of the procedure. So the guy's screen is ready to go he's in the cath lab you call the patient then gets randomized okay is a treatment or control. Now there's no time for the guy to have anything happened. So everybody that got randomized is gonna get treated or placebo, right? So and that's something I've had to explain. So this 565 patients is the intention to treat which is one way to look at trials. And then this set here the 537 is what we call the as treated or full analysis set. And it turns out in all the analyses there's no difference between intention to treat. I'll show you the full analysis because I think it's more meaningful to say this is what happened in the people it was defined by getting at least one injection. So if you got one injection you're treated and if you got no injections you're not. So then we have two groups 276 were controls and 261 are the NPC injected treatments. We stratified the patients in enrollment by class. So there would be an equilibrium between classes and then you say, oh, wait a minute there's 106 and 170. Okay later on during the trial there was an adaptive change that we did to just enroll class threes during the last year because as you find out if you enroll a bunch of class threes people start dying and having events and you run out of people that are having events because they've all had them. And if you do a time to first event analysis all your data has disappeared and you're sitting on nothing. So we needed to enroll more class threes. And so even though they were balanced in the first five years of the trial in the last year we enrolled just class threes. And obviously this is with blessings from the FDA, et cetera. Okay, so we'll look at the baseline demographics are basically the same in the two when you have this many patients you're really not gonna hopefully see a lot of differences. So here you can see the average age was like 62. The distribution of cardiomyopathy so there was a little bit more ischemic cardiomyopathy than non-eschemic. So it's about 60, 40, not quite 60, 40. And here you can see there were more class threes. I just told you we enrolled the last year just class threes. So wind up having a preponderance also like 60, 40 to the class three to class two, which is interesting. I'll show you some interesting things about that. And here you see about 40 few percent diabetics and amount of people around 55% that had revascularizations. And this is incredible. So 84% of the patients had either ICD or CRTD. So now we're dealing with a very modern well-treated population of patients all of which have defibrillators and to the next slide. If you look at the therapy they're all on very good medical therapy. So if you look at the RAS medications were over 90%, diabetics 90%, beta blockers over 95%, not the digits, but the digits in the 20s. And here, this is what I told you about in the beginning really SGLT-2s weren't even approved. So these are like a diabetic or two that maybe when it first came out got it for diabetes. And you can see statins here 65%. Again, the non-eschemics don't need statins, right? So they're not necessarily on statins. You can see that the overall ejection fraction was 28%. So we enrolled for less than 40 wound up with 28. And here you see the volumes about 150 endostolic volume, 200 endostolic volume. So that's a pretty compromised population. You start seeing events in people with endostolic volumes over a hundred. You can see the six minute walk of around 340. So that's pretty consistent as well. Here you have the anti-probium P's and the CRPs which are elevated. This wasn't in the presentation, just put it in here as a little extra color. It's kind of interesting to see if we look at class two and class three, there should be some differences, right? If you're enrolling correctly, there should be some differences. So if you look at the six minute walk, class threes walk less than class twos significantly so. The anti-probium P was significantly higher in the class threes. The CRP was higher in the class threes. I told you it's an inflammatory disease as was the renal function. So very nice and as expected, no surprises. Okay, so then we get to the wonderful part of this trial which is the primary endpoint. So the primary endpoint that I had originally made that the Mayan stroke, we changed when we did that reduction in the number of the trial to recurrent non-fatal heart failure events. So what that means is visits to the hospital for shortness of breath and to get diuretics because that's what the heart failure patients do. And as you can see, there is absolutely no difference. These cells are not a decongestive therapy and that's really not how they work. We thought that maybe on top of everything we might see an effect here. We were expecting to, we wouldn't have made this a primary endpoint but the primary endpoint is negative. Now that's a problem because the way rigorous science is structured, if you miss your primary endpoint, now everything after that is hypothesis generated, right? Now this is a new therapy. So it's very important for the, this is the largest trial of cell therapy by a lot ever done. So it's very important to kind of get your bearings and see if you have meaningful findings. And I'm gonna show you what I think are some very meaningful findings. So every endpoint that I'm gonna talk about though, this is not ad hoc post hoc analysis. These are all pre-specified endpoints with pre-specified analyses. And I'll tell you when they're not, there's just one. So heart attack and stroke, if you look at the overall population and you look on this panel right here, you can see over time, there's a separation, there's more heart attacks and stroke in the control population. There is a risk reduction of 65% in heart attack and stroke. So if you look at the numbers here, that's 4.6% of the NPC versus 13, 0.001. Okay, wow. Did I talk to you about a systemic effect of these cells on large vessels in the brain and in the heart? And this effect is due to a reduction in MI and a reduction in stroke, okay? So both of these things got affected. It's not one more than the other. So that's pretty interesting, right? If we look at the difference in then class two and class three, we see that this is basically present in both. So we have a 66% reduction in class two. We have a 65% reduction in class three. So this is a very nice time to first event analysis, by the way. Now, this bottom panel that shows these forest plots here, so everything on this side is benefit cells and here benefits control. But the reason this is done is this is a recurrent events analysis because the follow-up in class two and class three, remember I told you we enrolled class threes only for the last year. So the follow-up of class threes was shorter than class twos. So the mean follow-up of class twos was 35 months. The mean follow-up of class twos was 26 months. So what you do to make sure that you're not seeing crazy stuff is you normalize it for 100 patient years. And so this is looking at it this way, that difference in follow-up doesn't make any difference. So even looking at it like this, no problem. We have even a bigger effect, which is really nice. A 69% reduction overall in MI and stroke in the whole population. And you can see it's significant in both classes. Here's your P values and your hazard ratios. So that's kind of surprise number one. Okay, how about death? So we can divide death in a lot of things. So first of all, there's all cause death, okay? You died, suicide, got in a car accident, et cetera, et cetera. Then we can go to cardiovascular death. That's heart attacks, but also a vascular event, so strokes, okay? So, or not just heart attacks, anything that happens in the heart, okay? That you die from and strokes. And then you go to cardiac death with just things in the heart, okay? So we're showing you here cardiac death because it's kind of more meaningful, kind of separate out the vascular stuff from the cardiac stuff. But I have cardiovascular stuff in here as well. So this is, again, remember the primary endpoint, if all those recurrent events and everything, if you look at the whole population, there is no difference, okay? Interestingly, in class two, there is a very significant difference in death, in cardiac death, 57% reduction in death. In class three, no difference. So we can talk about hypothesis of which has happened, but I'm gonna show you what the real truth is in a little bit. It really isn't class two, class three, although you can imagine that class two patients have more viable heart. They have more heart tissue from which the cells to have an effect on, so, but we're gonna dig a little deeper in that and talk about that a little bit more. But nonetheless, this is a very interesting finding. And again, if we do, this is not recurrent events because death doesn't recur, right? It's only one time. So, but this is, again, normalized for follow-up over time for 100 patient years, and you can see it continues to be significant with a 58% reduction, and here you see the hazard ratios. Okay, this is the real story, and that's why in the beginning I was telling you about cells and inflammation, that's what these cells do, they're anti-inflammatory. So if we look, and so I'll take another endpoint, okay? It's a very commonly used endpoint. It's actually the endpoint that I think the FDA will want us to use moving forward. So it's a very significant endpoint, which is a composite of cardiac death, stroke, and heart attack, okay? So these are the big events happening to people. So if we just look at that, and if you look at this panel on the left here, this forget the right panels. This is in everybody, okay? So if we looked at death in mind, stroke, there is a 33% reduction when you've got these cells as opposed to being in control. That is a 0.02 p value, so it's very significant, 20% versus 30%. Again, that you could see the days here, I told you this is a mean 30 month follow up. This is a time to first event analysis. Okay, so then we said, well, and this is a pre-specified analysis. We thought ahead of time, well, we're gonna look at everybody according to their CRPs because a CRP is a good way to look at inflammation. And so we'll look at CRPs greater than two, greater than three, greater than four. Turns out it's all the same, and we used two. That's what he was using the Kanto's trial, and I think it doesn't make any difference, and two is kind of the cutoff, and that's what we had pre-specified. So look at this, this is amazing. So where is all the benefit of these patients from not dying, having heart attacks and strokes? It's in the patients that have inflammation. Is there any benefit in patients that don't have inflammation? No, don't give cells to people that aren't inflamed. Okay, so for the first time, we're able to nail the mechanisms and show this of how these cells work. They're doing their anti-inflammatory job. We know that heart failure is an inflammatory disease. We know that atherosclerotic is an inflammatory disease. And when you give anti-inflammatory treatment, that is more than one thing, that is a living cell that does a bunch of things, you get a significant effect. So this is the main story, but we'll look at some more stuff. Remember I showed you that a couple of slides back, cardiac death in class twos, right? So, and I told you, cardiac death, here's class two, but is it really class two or is it something else? Well, it's something else. Here's all the benefit, it's inflammation. So if this benefit back here was a 57% reduction in cardiac death, okay? Now we see, which is, this is incredible. This is a number needed to treat a four, okay? We see a 80% reduction in cardiac death in class two patients that are inflamed. If they're not inflamed, again, this is the same idea. There's no difference. Even in the class two guys, oh, well, but there, you know, no, if they're not inflamed, there's no benefit. It's the inflammation that does it and it does it in a very major way. This is an extra slide I had put in here just to show you the power of inflammation. So if you look at all, so all cause death is a lot harder to get a positive value in, right? Because you got people, there's, I can't remember the number, but people committed suicide and this and that and the other. Okay, so if you have a CRP greater than two, there was a 60% reduction in all cause death if you got treatment in cells in these patients. So I'm not trying to really cherry pick and show you this. I'm just trying to explain that inflammation is how these cells work and we consistently see this benefit across the board. Okay, then you say, well, okay, CRP, maybe this was wrong, right? Remember I showed you that CRP is produced by IL-6 and IL-6 is the real culprit and induces CRP production and liver. So guess what, we measured IL-6. And so this is kind of a complicated slide but basically this group that has all the events, this is the control with high CRP. So these are the inflamed patients, okay? And so they didn't get cells and they have inflammation. These three guys are either the non-inflamed patients that don't have events or they got cells and they're protected as I've shown you. Well, if you do the same analysis for IL-6, it's identical, it's the same thing. So it needed to be this way because if we have a difference in IL-6 doesn't show this, I'm in deep trouble. So again, it's very consistent one with the other. It is the inflammation and we've shown it. Okay, we'll finish up with safety. So importantly, there weren't any SAEs or treatment emergent adverse events associated with the cells, which is very important. And we've shown that before in NPC studies. And very importantly, and we won't go into this. I could do a presentation on this, is that there's really no immune issues. Everybody was tested. We did these tests to see if these cells, because after all their allergenic cells are from somebody else, are they causing any kind of problem? No, they're not causing any kind of problem. Okay, these cells really fly under the radar. And what I found incredible is the procedure, because you were, we took them to the cath lab, you're poking a catheter, and then when you're doing the injections, you're going, you're trying to appropriate the heart. Not really, but it can happen. And there was one perforation in all the treated patients. It's an incidence of 0.4%, which is the lowest incidence. So even though we did this at 51 sites, it shows that with good training and planning, you can really reduce the complications of a procedure. So it's a very safe procedure. And this is another interesting thing, is think about this. I'm talking about a follow-up of 30 months, and we did one procedure. Okay, you got to take intresto twice a day, every day, okay? So, and that's another point, that this benefit is on top of intresto and diuretics and SGOT2s, well, not SGOT2s here, but all the best medical therapy that we know how. So inflammation is different than congestion, volume overload. That's why we didn't hit the endpoint of recurrent non-fatal events, because that's not what these cells do. And so one thing that I've kind of come to a conclusion, is you kind of have to decouple this idea that in all these heart-fader trials, everything is always together. Well, if you're able to actually successfully treat inflammation, that's kind of a separate basket of things. So in conclusion from this trial, that we showed that the 150 million dose which we had gotten from our phase two dosing trial is safe, didn't cause any immune problems, which is very important. We showed that we missed our primary endpoint, that it doesn't help with non-fatal recurrent events, but we showed with a mean fall of 30 months, we had on top of guideline directed medical therapy, a decrease, a significant decrease in non-fatal immune stroke, a significant decrease in class two cardiac death, or with inflammation, and a significant decrease in the composite of death in mind stroke. And that the benefits of this therapy are really in those patients with inflammation. So, oh, this is sort of a summary slide that I had in here for like the press event. But, and it's, again, it makes the point about, here's the primary endpoint, it's congestion, we have no effect. Here are the other two endpoints, and it's really a local effect on the cardiomyocyte, on the microvascular. So we're having decreased intracardiac inflammation, neovascularization, things we haven't really talked about that cells do, cardiomyocyte survival, energetics, and then at the level of blood vessels, we're having a systemic effect where it was stabilized atherosclerotic plaques. This is likely due to the macrophage effect, I think both systemically and in the heart. Okay, so here I think I'll stop and take questions. Thank you very much.