Okay. I see the participant count has paused and it's 4:00 P.M., so I think we'll begin. Good afternoon, everyone. My name is Ellen Gurley, Manager of Corporate Communications and Investor Relations at Athersys. I would like to welcome you all to this special webinar, Rebalancing the Immune System: The MultiStem Cellular Platform for Treating Disease and Injury. Today, we will be hearing from two very talented scientists at Athersys, Dr. Willie Mays, Executive Vice President and Head of Regenerative Medicine and Neuroscience Programs, and Dr. Sarah Busch, Vice President of Regenerative Medicine and Head of Non-Clinical Development. Together, they will be providing an update on our pre-clinical programs and sharing some details on the exciting science that has been going on at Athersys over nearly the last 20 years. At the end of their presentations, we will host a short question- and- answer period. To ask a question, please do so by typing in the chat and we'll receive those on our end. As a reminder, the focus of our webinar today is science, so we will not be able to comment on any other business or financial related questions at this time. With that, Willie, I would like to welcome you, and you may begin with your presentation first. Thank you, Ellen, and thanks everyone for making time for us this afternoon. As Ellen said, I'm Willie Mays. I'm sharing my screen right now. I'm one of the co-founders of Athersys. I've been here since we named it. We're going to spend some time today giving a presentation that's a little different than probably what most of you have become used to, and that is doing a deep dive around the translational research that's specific to one of our clinical programs. Today, I'm going to show our safe harbor statement first and foremost. We're gonna get everybody starting from square one. I know we have old investors on the call, we have some new investors on the call, and we have some potential new investors on the call, as well as some other interested parties. What we wanna do today is really focus on the breadth of the science that we've generated using the MultiStem platform technology as opposed to doing a deep dive. Translationally, in the past, we've really focused on our key critical care indications like stroke and trauma and ARDS, and the science that supports the translation of the cells into the clinic on those indications. We're gonna talk about a lot of indications that some of you may not know we have done extensive work in, as well as a couple of indications, couple of technologies that you can use the cells for that I'm certain no one, not inside the walls of Athersys, knows that we can use the cells for. With that, just again, we're all starting from the same peg. The MultiStem cell therapies originally, it's the name we use, for the cells based off of the multipotent adult progenitor cell technology or the MAPC technology originally characterized by Catherine Verfaillie in 2001. We've spent a lot of time in the last 20 years learning about what the cells do, and just as importantly, figuring out what the cells don't do when it comes to, you know, affecting pathophysiology in a number of different indications. We've learned a lot about how to grow and expand the cells, and we've learned how to make the cells in a clinically significant way, in a clinically relevant formulation, with lots of understood, characterized product life. When I started, when Dan and I were talking, and he was like, "Yeah, I want you to highlight the entirety of the platform that MultiStem occupies," I needed to figure out exactly what platform meant from that standpoint. If you use the Google machine to figure out what a platform technology is, it basically spits out a number of definitions. In summary, it is one or more technologies that are the base or foundation for the development of multiple other applications or more advanced technologies. I believe we have already done that with the MultiStem platform. I know there is. I have got a lot of friends out there that have invested in the company. They get caught up in busting my chops and saying I am a snake oil salesman. I would hope to show you differently during this presentation. Platform technologies enable other growth and learning and other technologies to develop, and we believe that's what MultiStem does. First and foremost, you know, we have spent the last 17 years basically writing and receiving grants based around the use of the cells for the treatment of a number of different injuries and diseases. We applied for these grants, and we were in competition with other people that were submitting grants across a number of different applications. We received every grant we've ever written with these cells with the exception of one. We've gotten these awards from a number of Recording in progress. We've gotten these awards from a number of different funding organizations. These organizations aren't in it to support Athersys or to validate MAPCs. They're in it to cure diseases and advance healthcare for a number of different individuals in disease states. Again, we've been lucky, but we've also understood and learned a lot about the cells from the awards we've gotten from these organizations. We've done this in collaboration with some of the world-leading translational hospitals and universities. We're thankful for the collaborations we've had, the support they've given us. Again, they're not in it for us and the validation of the cells. They're in it for their own research and to learn more about the indications and the diseases they care about. We've been doing this for two decades now, and I would say the success we've had, the partners we've made, the partners we continue to have with a lot of these institutions and funding organizations should allay the fears of anybody out there that wants to think that what we're peddling is snake oil, because we believe that the cells work. I'm gonna go to my grave saying that the cells work as long as someone's willing to listen to me. Very quickly, again, from a platform technology standpoint, we've learned how to grow the cells, to optimize the growth of the cells, and how to manufacture the cells in very large quantities. This is something that gives us a distinctive profile compared to other allogeneic adherent cell therapies that are out there, and we can literally make hundreds of thousands of doses of clinical-grade product from a single 100 ml bone marrow donation. We have lots of intellectual property around everything we've learned along the way in learning how to mass produce the cells. We've learned how to make a more clinically applicable formulation of the cells. Rather than having something that required hours in a cell therapy lab to have to thaw, reconstitute, wash, and reformulate, we now just have a thaw and administer formulation of the cells. We can thaw the cells, take them up into a syringe, place them into a bag of saline, and get them to the patient in less than an hour. We've also developed, engineered, and have a prototype for a machine that basically is like a cellular ATM that could be stored in the pharmacy at any one of our clinical centers, called the SIFU, a Secure Integrated Freezer Unit, which can store the cells, warm them up upon being instructed to do so, and spit them out the front into the hands of the pharmacist, who could then go through the procedure shown on this slide. Again, other technologies that have emerged as a function of learning how best to utilize the MultiStem cellular platform. I'm really quickly gonna go over the acute CNS portfolio. It's the centerpiece of where we started our knowledge and how we began to utilize our knowledge in a translational way. A lot of you will have heard some of this before. We're not gonna go down a lot of rabbit holes. Very quickly, just gonna touch on some of the key points. Again, we're thankful for the funding agencies. I just did wanna highlight, though, you know, we wrote all of these initial grants within the span of about three to four years. By the time we were working on the first grant for the first indication here, for example, Hypoxic-I schemic injury was the first grant we received. We were also doing work in these other indications with other collaborators that I'll mention here in a couple of slides. That afforded us the benefit of being able to learn something in one indication, one translational animal model of acute injury, and then ask the question: "Geez, if the cells are working that way or doing that, how can we change maybe how we're thinking about some of these other indications, the way we're administering the cells, the number of cells we're administering, the timeframe for the cells?" There was a lot of synergy that was developed off of these first four core grants that really, I think, helped springboard some of our thinking and some of our discoveries relative to the cells. One of the technologies we used was basically microarray. It's looking at the nucleic acids from the tissues in the animals that we're evaluating so that we could really compare what are the differences between sham-injured animals and disease-injured animals, or injury in the animal, in the tissue, for example, in the spinal cord, in the stroke lesion, in the hemisphere of the Hypoxic-I schemic injury. Compare that to from cell-treated to saline-treated, and look for differences in gene expression and gene regulation. That really is what helped us begin to understand exactly what we believe the cells are doing and how they're modulating and interacting with not just one aspect of the immune system, but multiple different aspects of the immune system. I think when you're going to tackle pathophysiologies that are so large and all of the things that go wrong when you have a stroke, when you have a severe spinal cord injury or a traumatic brain injury, you better have a therapy that works in a multimodal way, in a very profound way, across lots of dimensions of the injury. We think that's one of the reasons why administering the cells early after an acute CNS injury leads to such beneficial outcomes. We're not the first people that were thinking about the spleen, and I'm not gonna talk about the spleen at all, except for the next three slides, four slides. The first observation that the spleen was critical in stroke was from the lab of Keith Pennypacker and Alison Willing, down at the University of South Florida. They basically showed in this 2009 paper, and other people at the same time were illustrating that the spleen was an important organ in the pathophysiology of stroke. If you look along the arrow at the top of the screen, the bright green line is dead cells. You can see in a sham-injured animal, there's no dead tissue. In the middle, the middle cerebral artery occlusion surgical model of stroke, you can see that that rat has lost basically half of the neurons in this cross-section. If you splenectomized the animals two weeks prior to doing the same exact surgery, you see a statistically significant decrease in tissue loss. We did the same experiment with Sean Savitz at the University of Texas (UTHealth) Houston, and published this in 2017. What you see is on the top panel, you can see that if you look at the brain three days after you induce the stroke, two days after when you either administer or randomize the animals to receive saline or cells, that there's the same amount of tissue loss. We induced a stroke. There's gonna be dead tissue, and at three days, doesn't matter whether you got the cells or the saline, you've lost roughly the same amount of tissue. If you look at other animals that were taken out to 28 days, you can see irregardless of whether the animals had spleens or did not have spleens, that there's less tissue loss in the splenectomized animals. Irregardless of whether there's spleens or there's not spleens, the MultiStem treatment was decreasing the amount of tissue loss in the brain. However, this is the critical slide that I think is lost on some people. You need to have a spleen for our cells to provide meaningful recovery benefit. If you look on the left, these are all animals that were randomized to get strokes and then either get saline or MultiStem, and you can see a statistically significant improvement in outcomes in the MultiStem-treated animal. If you splenectomized animals and did the same exact experiment, randomizing animals to get either saline or MultiStem two weeks after having their spleens removed, there's no benefit. This frustrates me constantly when I see people in the world of allogeneic adherent cell biology and various diseases where they talk about cells like ours. The MSC world talks about immunosuppression. The cells work by immunosuppression. The cells do not work by immunosuppression. They work by immunomodulation. They turn off the bad stuff faster and turn up the reparative aspects of the immune system, which we believe is catalyzed in the spleen, and we believe this figure illustrates that. I'd also like to highlight, we've spoken kind of in one-offs here and there about T-regulatory cells. Sarah's gonna talk about a really, we believe, important aspect of our cells, when it comes to the world of cell therapies relative to T-regulatory cells. I just wanna highlight across three different acute indications, T-regulatory cells, we see an upregulation of T-regulatory cells in the spleen of MultiStem-treated stroked animals compared to saline. We see a statistically significant increase in T-regulatory signatures in the blood compared to saline-treated animals in the spinal cord injury world. We see the upregulation of T-regulatory cells compared in MultiStem-treated animals compared to saline-treated animals in not only the blood but the spleen in the traumatic brain injury model. We believe T-regs are important, and you're gonna hear about T-regs a little bit more in just a second from Sarah. Then just to end real quickly with some real, we think, important data from each of these three other acute neurologic indications. In spinal cord, money that was granted to us by the Ohio Third Frontier, we published a number of papers in collaboration with Dr. Jerry Silver and researchers up at Oregon Health & Science University, who replicated the work that we did with Dr. Silver. What you can see here on the left is that if you administer an IV dose of MultiStem 24 hours after inducing a spinal cord injury, you see almost immediately an improvement in gross locomotor behavior comparing MultiStem to saline-treated animals. It's even more profound when you're looking at locomotor, fine locomotor behavior, the ability to use the forepaw in very specific ways. When we look at traumatic brain injury, again, funded by a U grant from the National Institute of Neurological Disorders and Stroke, we've published multiple papers. I believe we're up to six now with Dr. Chuck Cox, our collaborator down at UTHealth Houston. Very important piece of data here on the left. You can see a statistically significant decrease in microglial activation. Microglia are the basically the immune surveillance cells in the central nervous system. You can see in a sham-injured animal, there's not a lot of activated microglia. If you induce a traumatic brain injury, that's CCI, you can see there's an upregulation at a low, suboptimal dose of MultiStem cells, we don't see any difference. But at a therapeutically comparable level of cells, the CCI-10, you can see that there's a statistically significant increase or decrease in microglial activation. This leads to a statistically significant improvement in memory functions, one of the major side effects in traumatic brain injury patients. To tie some of this together, we've done a lot of work in the hypoxic ischemic injury space with multiple collaborators, published multiple papers, received a U grant funding from, again, the National Institute of Neurological Disorders and Stroke. Just to show you so. We are collaborators with Dr. Ward, Dr. Jim Carroll down at Medical College of Georgia, and with Dr. Boris Kramer and Dr. Reint Jellema at Maastricht University in the Netherlands. Just to show you here again, bottom panel C, you can see these are in utero- injured animals. These are animals that have not yet been born. They undergo a surgical hypoxia surgery, and then we administer the cells acutely, and then 24 hours later, and you can see in these animals, you see a statistically significant decrease in activated microglia in the subcortical white matter. We see a statistically increased level of white matter and the specific protein is something called myelin basic protein, one of the major proteins that's responsible in myelinating neurons in the brain. We see a statistically significant decrease again in the Iba1 response to this antibody in the fetal sheep. From a translational standpoint, this leads to a statistically significant decrease in not only seizure number, but actually the severity of the seizures in the brain of these fetal sheep. That's gonna correlate to improved outcomes, we believe, in hypoxic ischemic injured children who also undergo seizures. I'll talk more about seizures at the end of the talk when it comes to epilepsy. Just to wrap it up here, again, we really believe that there's a lot of applicability using these cells in a subacute timeframe after acute severe neurologic injuries. We really think that the use of the cells in that timeframe leads to a decrease in the negative aspects of the pro-inflammatory response and a more rapid increase in the reparative aspects of the neurologic response. With that, I'm going to hand it over to Sarah, and she's going to talk about some of the other applications of the cells. Sarah, whenever you're ready. Thanks, Willie. You see my slides okay? Yep. Great. Hi, everyone. I'm Dr. Sarah Busch, and I'm gonna be going through some of the most promising preclinical programs in the non-CNS space, as well as organ transplantation and a few other acute indications. I'll just echo Willie's sentiment that we've been really fortunate to collaborate with amazing scientists across the globe over the years to advance these programs. Really excited to get to speak to you all today. In collaboration with Dr. Robert Miller, we have investigated the ability of MultiStem to exert benefit in multiple sclerosis. Many of you may know that MS is a disease of the central nervous system in which immune cells lead to demyelination and loss of axons, which disrupts the flow of information between the brain and the body. There are already several FDA-approved disease-modifying therapies, for multiple sclerosis, for relapsing remitting specifically. However, there's still a significant unmet need, in the more progressive forms of MS and the need for those therapies to really, help to resolve preexisting CNS damage. As I said, we've worked in a number of different models with Dr. Miller, including, what I'm showing here, which is, excuse me, experimental autoimmune encephalomyelitis, mouthful, also known as EAE. In this model, we were able to demonstrate a dose-dependent benefit, of intravenous administration of MultiStem, which we showed led to reduced numbers of lesions and a reduced size of lesions in the CNS. Hopefully, you're gonna be seeing a video here of an EAE-induced animal that was only treated with vehicle. You can see a very dire state in which the animal on the left has lost function of its hind limbs and tail. In contrast, you can see an animal on the right-hand side which has been treated with MultiStem, and you can see there's just far superior function. The animal's able to move around the cage, use its hind limbs, rear, and in general, has just a much improved overall function. This is really exciting to us, and I wanted to show a visual of really what that looks like in an animal model. We repeated that study a number of times, modifying various aspects of the experimental design. One important observation that we made was that the timing of MultiStem administration was really important. If you gave MultiStem cells too soon, the cells were not effective. I think that mirrors something of what Willie showed and touched on really, really briefly earlier in spinal cord injury, and in which we've seen that the cells are not responding to they're not responding to the injury, they're responding to the body's response to the injury. We think that that's a really critical conserved aspect of how the cells are working and what they're able to sense and how they can respond. We've also looked in a more chronic subchronic, chronic timeframe, a few weeks after the initiation of EAE, and we saw impact in this timeframe, which is really encouraging, and showed us, you know, that there was an ability to intervene at a later stage. When we were looking more into this model, you know, we wanted to understand how much of that was due to immune modulation and how much of that was due to more driving of repair processes. We did full gene expression arrays across many different organs. All I'm showing you here is data from the spinal cord. Here we showed that there were a number of things called upstream regulators. That's genes that are known to drive the expression and influence other genes, essentially. These upstream regulators were strongly influenced by MultiStem. I'm showing you just a couple examples here to proinflammatory gene families and to CNS health and function gene families. Those inflammatory modulators were downregulated by MultiStem, as we would hope to see, and those indicators of CNS health and function were upregulated by MultiStem. We also examined the impact of MultiStem in a model called LPC or lysolecithin. This model results in a rapid loss of myelin and oligodendrocytes, those are the cells that produce myelin, in really a focal area. Just in one specific spot, so you can look really closely at what's going on in the lesion environment. Interestingly, what we saw in this model was that intravenous administration of MultiStem did not have an impact on remyelination. I haven't shown that data here. With direct administration into the site of the injury, we saw a striking increase in the amount of myelin. This is, you know, really encouraging to us. In this model, we were unable to dissect an impact of the immune response as there was still some inflammation ongoing in the spinal cord at this time, and impact on remyelination. For that assessment, we moved into something called the Cuprizone model, which is more representative of the chronic setting that I was referring to earlier, and very little inflammatory component at this stage of the disease. Here, again, we saw no impact of intravenously delivered MultiStem, but we saw an increase in remyelination with the direct administration of MultiStem into the ventricles in the brain. A slightly different approach, but it showed that the cells themselves, MultiStem, was able to drive remyelination in the absence of, you know, that direct immune response having an impact on them locally. Finally, we researched the impact of MultiStem on those oligodendrocytes or the progenitor cells that actually generate the myelin, provide the support for axons. What we found was that MultiStem secreted factors actually increased these cells in vitro, and they promoted their maturation. You can see how much different they looked. They're promoting their ability to produce myelin, which we think is really exciting as a basis for further investigation, not only in multiple sclerosis, but in other diseases as well. I now want to touch just briefly on two other CNS disorders that we have done some initial work in. The first being Parkinson's disease. Again, many of you may know that Parkinson's is a progressive disease that occurs when specific populations of nerve cells that produce dopamine are injured or die. This causes movement problems that are associated with Parkinson's disease. We used a model here in which an agent called 6-hydroxydopamine was injected to destroy the specific population of dopaminergic neurons. The animals then were treated IV with MultiStem or a vehicle, and we saw formation of new neurons in the striatum of just the MultiStem-treated animals, which was really exciting. When we looked at the gene expression in multiple tissues, we found indications of immunomodulation that was consistent with what we had seen previously in many other disease indications that we've gone through with you today, that are, you know, really conserved across those key different aspects of the MultiStem cell platform. We've also done some initial pilot work in Alzheimer's disease, which is the most common cause of dementia. This study was done with a grant from the National Center for Regenerative Medicine here in Cleveland. Here we utilized a mouse model called AICD transgenic mouse. These mice have features including tau pathology, aberrant neural activity, memory deficits, and neurodegeneration that show up in an age-dependent manner, so you know, more relevant to the Alzheimer's disease state than some other models. Here we examine the effects of, again, intravenously administered MultiStem to these animals. We found that they had a significant impact on the activation of microglia, which is a mechanism that we've extensively examined in traumatic brain injury, as Willie showed you briefly in some of his slides earlier. Again, something that you know, we've investigated previously an effect on cells in the brain despite administration of the cells intravenously. That's really interesting to us. Overall, in the chronic and progressive CNS space, we've shown that MultiStem exhibits a lot of disease-modifying impacts that we think represents opportunity for future development. We're really excited to see what the future will bring with those indications. Now I'm gonna shift gears slightly into the realm of organ transplantation and tolerance. Many of you know from our previous disclosures about our advanced clinical work in acute respiratory distress syndrome or ARDS. Excuse me. We've also investigated the ability of MultiStem to preserve and improve the quality of transplanted lungs and other organs, which I'll talk about in a moment. A common cause of failed lung transplantation is inflammatory and immune mediators that can really damage the lung in the acute timeframe post-transplantation, so once there's actually been a transplant. In our studies with our collaborator, we were able to show that human lungs that were isolated from organ donors that had inflammation prior to those lungs being used in transplantation were able to be modulated by MultiStem. We looked at administration of MultiStem to one lobe of the lung and vehicle to administration of the other lobe of the lung, which provides a nice internal control in the system. What we found was a reduction in inflammation in the MultiStem-treated lungs and a particular effect on the numbers of macrophages, which are an important cell type that we've seen modulated in many different disease indications. This is just showing you the modulation of those macrophages, kind of, a summary of the reduced secretion of pro-inflammatory cytokines that we've seen throughout many disease and injury areas and increases in reparative type macrophages, as well as a reduction in the ability of macrophages and other leukocytes to actually get into the site of injury. We're reducing their ability to pass through endothelial cells and exert, you know, an impact immediately at the site of injury. Also in the organ transplant space, we've collaborated with other leading researchers in the renal area at Newcastle University, and these researchers have been, you know, focused on the impact of kidney health following transplantation. You can see here that there's a huge number of Americans that are on the waiting list for a kidney transplant. A significant number of people dying on the waiting list for a kidney transplant, so it's a very serious unmet need. The group in Newcastle has been working with a technique to better preserve those donated kidneys, keeping them alive outside of the body in a normothermic machine perfusion circuit. We were able to harness this technology and then add MultiStem to it, essentially. We're adding the cells into the end of the circuit and then looking at the impact on the health of the kidneys. Looking at, again, pairs of kidneys, we were able to see that the kidneys that were treated with MultiStem became more transplantable. They're making more urine, they had better blood flow throughout the kidney and overall just less inflammatory ischemic damage. Therefore, you know, we're dramatically increasing the ability to, you know, transplant an organ and not having to worry about treating the whole patient, or giving added immunosuppression. That's something that me and the clinicians that we're collaborating with continue to be really hopeful about. This is another model of transplantation that isn't talked about too much, and this is a model of heterotopic heart transplantation. This was a really exciting collaboration, in which we were able to show that MultiStem can be used to promote tolerance and acceptance of a donor heart. You can see that, what we're calling the primary transplant on the left. You know, I think probably most excitingly, however, despite, you know, the primary transplant effects were exciting, but, potentially most exciting was the ability to show, that when there was secondary transplant, so taking the heart that was accepted in the first animal and transplanting it to a second animal, another naive animal, that heart was accepted with no immunosuppression, no immunosuppressive drugs, whatsoever. This was really exciting to us and again, to our collaborators, to be able to show that you could potentially reduce the number of those, you know, quite serious drugs that need to be given after a transplant. In this study, we also showed the critical nature of macrophages to the induction of that tolerance of the organ, as well as T-regulatory cell induction, which was a conserved mechanism. This brings me to an important program that we've developed in collaboration with researchers at King's College London, a T-regulatory expansion platform. T-regulatory cells Willie touched on earlier, I've touched on a couple of times, but this just shows you an overview of the many ways that they can impact the immune system, and drive a more positive or regenerative immune response. These cells are being developed in their own right as a novel therapeutic approach. We've previously published a lot of work. Alice Valentin-Torres here at Athersys drove the work around understanding the induction of T-regulatory cells by MultiStem. I won't go through this in any detail today, but suffice to say, concurrent with this development of our understanding of mechanism, we developed a MultiStem and regulatory T-cell co-culture platform. Again, this was in collaboration as well as with researchers at our wholly owned subsidiary, ReGenesys. This expansion platform system is a bit complicated, so I won't go through it in too much detail again. However, suffice to say, current clinical trials utilizing these T-regulatory cells are a challenge because it's difficult to manufacture enough T-regulatory cells to give a sufficient dose. Therefore, we have been looking to drive the expansion of T-regulatory cells for adoptive cellular therapy with MultiStem. We successfully showed that these cells, which we call MultiReg, they're able to increase the yield of these T-regulatory cells in manufacturing and reduce the time to establish a target dose of cells that would be given to a patient. Really interestingly as well, MultiReg cells were able to be expanded from patients with autoimmune diseases compared to matched regulatory T-cell lines. This allows for the expansion of a stable and effective regulatory T-cell product from many patients that are in dire need of this cell therapy. Finally, I'll give a brief overview of the work that we've done in the acute non-CNS space. We very recently announced the results of a radiation countermeasure study that was conducted in collaboration with the Armed Forces Radiobiology Research Institute, or AFRRI. We've actually been conducting research relevant to acute radiation syndrome over several years. Even back before these collaborations with AFRRI and NIAID, we were working in the space of hematopoietic stem cell transplants and graft versus host disease. We even completed a clinical study which showed favorable tolerability and promising results as well. For those of you who are unaware, acute radiation syndrome is an acute condition that comes from irradiation of the body by a high dose of penetrating radiation over a very short period of time. At lower doses, you see bone marrow damage that can ultimately be lethal without intervention. Here we looked at the efficacy of intravenously delivered MultiStem after acute radiation syndrome and found that MultiStem cells increased the survival of animals that were treated with MultiStem, resulted in higher body weights, which I'm not showing here, in those surviving animals, and positive trends in recovery of the hematopoietic system. This histology that I'm showing is from a prior study that we conducted in the same model. You can see the sternum of these animals treated with MultiStem, demonstrating a really dramatic improvement in cellularity. We're really encouraged by these results and plan to consider doing future studies in this area. Willie has spoken extensively in the past in previous presentations about our phase II clinical study in trauma, which is actively enrolling at UTHealth. This trial is comparing mortality and the incidence, severity, and duration of inflammatory complications and kidney injury, which is, I believe, a very important endpoint that we have a lot of confidence in given the data that I've shown you across that space today as well. Now I'm gonna turn it back over to Willie to go through one more disease and injury area that we're pursuing. Thank you. Thanks, Sarah. Let's see here, make sure I have the right. Let's see. There we go. Full screen. The last aspect that I'm gonna talk about, let's talk about two other platforms that we have, that basically deal with non-human MAPCs, as well as a novel targeted identification and validation aspect of the cells. The reason we learned about this novel application of the cells was through a collaboration we did with a large biopharma. Epilepsy is a horrible disease. There's acute forms of it. When you're having a seizure, it's a full on neuroinflammatory crisis, but the people that have the periodic seizures live with it their whole lives. Some people are refractory to some of the drugs. Some of the new drugs that are out there cause significant problems. When we were working with the company we were collaborating with, they used a multi-drug sort of model for inducing seizure activity in the brain of rodents. You give a drug, you wait 30 minutes, you give a second drug, and then two hours later, the animals start to have seizures. You moderate some of the seizure activity with another drug. Then we waited four hours, and 24 hours later and gave two doses of the MultiStem cells intravenously. Basically, there were two identical experiments done three months apart. You can see that the administration of MultiStem in Red, in experiment 1 and in experiment 2, leads to a decrease in the severity of the seizures and an offset in the timing when the seizures first occurred. When you add or you do the composite of all the animals in the bottom here, you'll get this sort of one-week experiments 1 + 2, and you can see again the offset. This was statistically significant. There's a number of different stages for seizure activity. The higher the number, the worse the seizure activity is in the animal. You can see there's a statistically significant decrease in the worst phenotype in the MultiStem-treated animals compared to saline, and a statistically significant upregulation in the mildest form of the epileptic seizure activity. We also preserved there was a lot of this significant decrease in lethality in the MultiStem-treated versus PBS animals. That was great. We hit a lot of the endpoints that we were looking for in the collaboration. After we were done with the experiment, we asked them, you know, "Can you harvest tissues so we can go back, run home to mother again with the microarray experiments?" Basically, what we did was we got all the microarray data from the tissues we were interested in, and we had some of our collab or some of our lab mates in ReGenesys, specifically Annelies Bogaerts. We didn't tell her what was going on. She didn't know anything about the outcomes, and we just had her evaluate the microarray data from the brains of the animals. What came back was we saw lots of changes in the MultiStem-treated versus the saline-treated animals. We were able to identify lots of targets that were in the literature that were well known to be targets of epilepsy drug discovery efforts across multiple different biopharmas. That also gave us the ability, and here's an example of that. Here, these are all genes, and I have those blocked off for our own safekeeping at this particular moment in time. You saw that our cells were affecting a lot of well-known targets in the world of epilepsy. What the other thing was that was interesting is, as we started to go down the rank order of the genes that were meaningfully changed by an administration of MultiStem, we ended up finding all kinds of other genes, that are logically implicated in epilepsy or could be novel target candidates. Just to convince ourselves that this was something interesting, we went back and we had the same sort of analysis done on some of the MS tissues that Sarah spoke about. Sure enough, we were able to see that MultiStem was affecting a number of known targets that were being sort of focused on by some of the big pharmas in the world when it came to MS. Likewise, when we looked at some of the genes that weren't known to be druggable targets, there were a number of other genes that came up that certainly appeared to be implicated in MS pathophysiology. That's another application of the cells as a platform that we can do traditional novel drug target identification with in the appropriate animal models. Finally, just to highlight roughly 10-12 years of work that were done by our colleagues over at our European office in ReGenesys, this work that was led by Annelies Bogaerts and David Craeye. If you can find a MAPC in a human, you can likely find a MAPC and mass produce a MAPC in other species as well. The group over there looked and found and produced MAPCs from both feline, canine, and equine donors, began to do basic disease-modifying research in a number of different indications. I'm only gonna focus on some of the dog work here. This is for anybody that's had a dog and a dog that lived to be 12 or 13. You know, they start moving more slowly, going up and down stairs in a more labored way because they start to suffer from significant joint disease. This was a surgical model of joint disease, and you can see on the left-hand side that the intra-joint administration of MAPC compared to PBS led to a decrease in severity scores in the histologic index that was used to grade the severity of the lesions, and that only animals that received canine MAPC responded in this model. When we looked at some of the cytokines and some of the proinflammatory mediators, you could see that they went up as a function of time in the joints of the animals that received saline as opposed to the animals that received a MultiStem administration. Of course, we saw that there was an injection of T-regulatory cells in the canines treated with MAPC compared to the saline treatment. With that, we wanna save time for questions. I just wanna take a moment. Been a lot of turmoil at the company that I think we're headed in the right direction now, but we had a lot of restructuring, and we had to let go of a lot of good people, and I wanna make sure we say thank you to all the scientists here at Athersys and ReGenesys for all of their hard work for 20 years. I wanna thank the academic collaborators. I wanna thank the funding agencies who made some of these studies possible. Obviously on the other end, I wanna thank the clinical teams who continue to work with us to treat patients with MultiStem and obviously those patients and their families. With that, if there are any questions, I will stop sharing and see if anybody has written us anything. I have not seen any Q&A come through yet. Ellen, do we know if it's enabled? If there's any questions? Yeah. The Q&A portion should be enabled, yes. Thank you. Yes. A non-scientific question is the first one, and so we won't be answering that here. Thanks, Phil. Yes. I got a question from a well-known, I believe former investor in Athersys, and we did seek CIRM funding, and we sought CIRM funding twice. Once for funding in the world of the ischemic stroke trial early on, and once in the translation of the traumatic brain injury work into a clinical trial. We received a score that was one point below the fundable range both times. We were in the, I believe, in the 95th percentile for scoring on both of those funding calls, but we didn't receive funding from CIRM at that time. That doesn't mean we can't go back to CIRM, and it's something we've talked about internally, but at this moment in time, we have not applied for any more funding. A question from Greg, how will you prioritize these programs? I think that's really considering where we are right now, Greg, a function of who knocks on the door or who picks up the phone. I mean, in the past, we were, I believe, a little more reluctant to wanna partner these out on kind of a one-by-one basis, but I don't believe that's the way Dan's thinking about things anymore. I think those are any and all of the things we talked about today, I believe could be partnered, just a function of who's interested. Are there any trials expected to be initiated in the near future for any of these? We would love to. We would love to fund a lot of these in the clinical setting. As a matter of fact, I know the National Institute of Neurological Disorders and Stroke are fairly well chafed with me because we received the U grants in both, TBI and hypoxic ischemic injury and pretty much got the ball across the goal line in both of those, but we haven't run a clinical trial. At the time, we didn't have the pockets deep enough to run another clinical trial than the ones we were conducting, but we would certainly like to get back to those. In both of those cases, we had formal pre-IND discussions with the FDA as kind of the final checkbox to complete the grants, and we did both of those. Let's see. We do not have any grants currently submitted. Since we reorganized and went more streamlined, most of our efforts really are in the world of completing clinical enrollment in the MASTERS-2 trial and having ongoing discussions with those interested in having discussions with us. Which programs would you consider most de-risked? Well, TBI. When you put trauma in its totality into a bucket, it's the third leading cause of mortality in the United States, and it's the first leading cause of mortality up to the age of 45 and then again after the age of 75. That is a pretty big market, and TBI makes up a significant portion of trauma, quote-unquote, in general. It's been de-risked, and we've had the FDA. We've had a formal pre-IND. We're ready and rolling when it comes to TBI. I have a question here that says, "Can you comment on dosage within and between diseases and the toxicity results?" Yeah. We've done for every one of the indications that we move forward into clinical trials, Steve, we do a full-on workup to make sure that we're not leading to anything toxic. We've had walk-in dose escalations in most of the indications early on, just to make sure that, you know, it's one thing to treat an animal in, for example, ARDS with your cells, but when you have a lung disease, you wanna make sure that when you're giving an IV administration of something that passes through the lung, that you're not exacerbating anything. I might add to that, Willie, too, just in terms of between the different disease conditions, that some of the diseases and injuries we've talked about today require far fewer cells. Like the solid organ transplant, for example, ex vivo treatment of just a kidney requires, you know, far, far fewer cells. We're looking at on the order of 50 million cells. So it's, you know, just a drop in the bucket compared with what we were looking at from an IV administration to the whole human being. So it definitely varies, and we're taking it into account and examining the different profiles for the different indications. Yep. Great job. Sarah, there's one here from Carl, that, I know we talked about and thought about. Mm-hmm. I'm not sure that there's an answer. If you wanna go ahead and. Oh, it's jumping around. Yeah. Sorry, one second, Carl. Plausible way to use IV administration of MultiStem to induce myelination for indications such as AD or PD. Yes, sorry. That's what you're talking about, Willie. We have talked about that. We've begun exploring it in a research and development fashion. There were a number of publications that came out suggesting that T-regulatory cells could actually drive remyelination, less myelin. We were very interested in that hypothesis, and it would make perfect sense with a lot of the work that we showed you today. There's definitely a plausible way to envision that. Yeah. Let's see. Yeah, so here multiple doses may be optimal for treating chronic indications? I totally agree, Nick. I mean, that's one of the things. Once we figured out kind of how the acute scenario was working, we ran around and chased the acute scenarios while we continued to do basic research with our collaborators and in our own labs on chronic indications. That absolutely may be the case that multiple dosings. There's some other companies out there that have developed sort of devices that may make treating chronic injuries or chronic conditions that are loaded with cells but aren't implanted into the body. That may be a possibility as well. Let's see. Let's see. It's hard to read and come up. Looking at a repair and plasticity. In this respect, the brain is actively undergoing changes over a longer period of time. Can you go into detail describing the changes happening in the brain that is leading to improvements in the clinical trial stroke patients? Yeah. You know, that's one of our hypotheses and one of the things you heard us mention several times today, microglia. Sarah did a lot of work early, before she ever joined Athersys, looking at the glial scar. Basically, there's a wall put up when you induce an injury in either spinal cord or in stroke. Axons are sensitive to the presence of activated microglia/macrophages, and when you put down something called a proteoglycan, the axons will pull away or recede. This glial scar is built up and basically walls off the injury from the non-injured brain. We believe when you administer our cells early, you minimize or negate the formation of the glial scar so that the axons retract but then, as a function of time, will eventually find their way home and be able to form a healthy neural circuit again. Let's see. What indications are you seeing the most interested in? Well, we've had interest in most of the things we shared today with you at one time or another. Dan asked us to put this presentation on so we could re-energize and freshen up, I think, the perspective of maybe those interested parties who never knew or didn't know all the things that our cells could do. Trauma should move quickly. We're enrolling in the second cohort in the trauma trial, and after we're done with the second cohort, there'll be a review between us, and some stuff we'll have to submit to the FDA to move then quickly, hopefully into cohort three. Then it would be to move as fast as we possibly can. I mentioned the trauma trial. That's pretty much it, I think. We're just past the top of the hour. So I'm done and certainly appreciative of the 100 of you that were on the line at one time. I really appreciate everybody making time for this. Sarah, Ellen, any last comments? No, I think you covered it. Thank you so much, everybody, for giving us the chance to speak with you. Thank you. Thank you, everybody.