...and welcome to the Jefferies Global Healthcare Conference. My name is Emily Lynch, with the Jefferies Investment Banking Team, and it is my pleasure to introduce Laura Niklason from-- CEO of Humacyte. Hi, everyone. Thank you very much, and thank you so much to the Jefferies team for inviting us to the conference. We've had great meetings today. So I'm going to just bring you all up to speed on Humacyte, which is really a first-in-class technology and company and platform. We are a platform, and so we have multiple product candidates in development, both in clinical and preclinical development. But I'm gonna focus mostly on the technology platform and our lead indication because we're very excited. We filed for approval with the FDA in our lead indication last year, and we've got a PDUFA date upcoming in August. So I'll walk you through that and then through some of our commercialization activities. So, as I mentioned, Humacyte has developed truly a new platform technology. This technology allows us to produce engineered blood vessels, but also other types of tissues that really function as spare parts for patients. These engineered tissues are available off the shelf. They're made from a cell bank. We don't have to take cells from the patient in order to make these. And this just advanced all by itself. Isn't that interesting? We don't have to take cells from the patient to make these. We make them from a cell bank, but once our tissues are implanted, they repopulate with cells from the patient, and they become the patient's own tissue over time. We believe that this repopulation confers durability and also a resistance to infection, and what that means is that these vessels can become essentially new arteries for the patient that they didn't have before. We are a first-in-class technology, but we have a lot of validating partners and data. In particular, we've been granted priority review for our Biologics License Application, or BLA, with the FDA. Again, we filed that in December. The BLA was accepted in February, and we have a PDUFA date on August 10, just two months away. We also have partnerships, important clinical trial partnerships with the Mayo Clinic. Our largest investor is Fresenius Medical Care because one of our early indications is in using our engineered arteries for patients who have kidney failure, who need access for hemodialysis. We also have a partnership with the U.S. Department of Defense, who's funded some of our work, and in fact, the U.S. Department of Defense named our engineered vessels as a top 5 priority to gain FDA approval so that they could have access to them to treat wounded war fighters. In our pipeline, we're also using our vessels to deliver islets, which are the parts of the pancreas that make insulin. We're, we're using our vessels to deliver islets, ultimately to treat patients with Type 1 diabetes. This is a very high-level overview of the technology platform that underlies our clinical stage programs and all of our preclinical programs. Essentially, Humacyte has a proprietary process where we've developed a cell bank, and we have enough cells in hand for the next 20 or 30 years. When we want to make a batch of tissues, right now, we make 200 tissues at a time, we'll take one small vial of cells, and we'll thaw those cells and grow them. And then we'll seed them onto scaffolding that's contained inside a bioreactor. The cells adhere to the scaffold, and then over a period of two months, they grow to form a new artery. After the artery has been grown inside the bioreactor bag, we then inject essentially detergent solutions into the bag, and what those solutions do is they wash the cells out of the tissue. So what does that leave us with? That leaves us with an engineered human tissue that we've grown from scratch, from cells, but it contains only extracellular matrix proteins, like collagen, and it doesn't have any cellular material left. We believe that means that when implanted into patients, there's nothing for the patients to reject. These are non-immunogenic tissues. In fact, over more than 10 years, we've treated nearly 600 patients and with a variety of diseases. We have more than 1,000 patient years of exposure, and we have never had an episode of clinical rejection. So one thing I'm gonna do is, we're gonna do a little bit of show-and-tell. I have an engineered vessel up here, that's contained within the bioreactor bag, and I'm gonna pass this around. I know this normally doesn't happen, but we're gonna do it. So this plastic bag is the bioreactor bag where we grow the artery. The artery itself is this white tube that goes from basically the bottom of the bag to the top of the bag. We have had some people think that this whole plastic thing gets implanted into the patient. That's not the case. But what goes in is this engineered artery, and you all can pass it around. So as I mentioned, we have multiple indications that we're working on clinically and preclinically. That engineered vessel that's being passed around right now is being studied and has been studied and is being studied in three different indications: vascular trauma, traumatic injury, which is our first indication that we filed for approval with the FDA. We also have a phase III program underway in using the vessel to treat patients with kidney failure who need dialysis access, and we have phase II programs underway, where we've used that same vessel to revascularize patients who have blockages in their leg arteries, who suffer from peripheral artery disease and who may face amputation because they have no vein to revascularize their legs. So this is just showing what happens in patients after these vessels are implanted. After implantation, as I mentioned, cells from the patient migrate in, and they take up residence in the wall of the HAV, or Human Acellular Vessels. This process takes months, but it gradually turns this implant into a living artery, which is the patient's own artery. We believe that this repopulation, as I mentioned, confers both a resistance to infection, because it becomes a living tissue that resists infection better than a plastic implant, but also durability, because the patient's cells become part of the tissue and maintain the tissue over time. So our first indication is in the treatment of traumatic injury. This indication, as I mentioned, has been supported by the U.S. Defense Department. In fact, they funded part of our clinical study that has gone into our BLA filing. Essentially, in traumatic injury, when a patient arrives in the emergency room at 2:00 A.M. with a gunshot wound or a car accident or what have you, these patients typically are bleeding excessively. They'll often have blood flow cut off to whatever part of the body we're talking about. And the wounds are typically contaminated. These are not sterile wounds. There's shrapnel or bacteria or dirt or whatever. So these wounds represent a difficult problem for trauma surgeons and vascular surgeons because they need to restore blood flow quickly, but they need to do it with a conduit that hopefully will resist infection, that will not become infected if they put that conduit into this contaminated wound bed. So right now, there are three options. The surgeon can spend an hour taking vein out of the leg of the same patient, further injuring that patient, tie off the side branches of the vein, and use that to repair the injury. If the patient doesn't have vein, then the surgeon can reach up on the shelf and pull down a plastic graft, but that has risk of infection for all the reasons I've mentioned. Alternatively, if the surgeon doesn't think that either of those two options work, then you can amputate the limb, and that's the current state of play. This just covers the repopulation that I mentioned earlier, and so I won't go into this slide. But it was really on the basis of the inherent, the properties and characteristics, our product profile of our engineered vessel, combined with the needs of the trauma population, that led us to initiate and then complete this Phase 2/3 trial in traumatic injury. So this is a trial that we designed working with the Defense Department and also with the FDA, where we treated a total of roughly 70 patients who had all sorts of traumatic injuries. They would, they would present to the emergency room, and because such patients are oftentimes literally bleeding to death, you can't you can't randomize those patients to one, to one treatment or another. So these patients were consented, and they all got treated with our engineered vessel to restore blood flow. As a comparator, we agreed with the FDA that we would look at published literature on how patients do if they have to get a synthetic graft, a plastic graft, used to treat their injuries. So it's a historical comparator versus a single-arm study. Sorry for the gross pictures after lunch, but these are just some of the wounds that we treated in the trial, and these are not the most heinous, trust me. I'm gonna skip ahead to the second part of the data that went into our BLA, and then talk about sort of the entirety of the package. So while we were doing this Phase 2/3 trial in the U.S. and in Israel, the war in Ukraine broke out, and a month after the Russians invaded, we started getting requests from Ukrainian surgeons asking for our engineered vessels to treat wounded warfighters. So we worked with the Ukrainian Ministry of Health and also with the FDA to get permission to send vessels into Ukraine and use them in the wartime setting. We then got the vessels there. Logistically, that was nontrivial, and then we trained our surgeons over Zoom because we couldn't go there to train them on how to do the surgical implants. So after all of that, surgeons in Ukraine treated a total of 19 patients over a year-long humanitarian effort, and you can see the outcomes there. Out of those patients, 94% retained blood flow through the graft after a month, which was our primary endpoint. But in addition, none of those patients suffered amputation, and none of those patients suffered infection of their vascular conduit. And that was an impressive result, given the fact that this is an austere setting, a wartime setting, and the fact that we had to train our surgeons over Zoom. So the FDA, when they heard about these outcomes, asked us to combine the outcomes from Ukraine with the outcomes from our clinical trial that we had completed in the U.S. and merge those together as a single civilian and wartime dataset, and that's what we did. And then we compared those against outcomes from the literature on how well patients do when they get a plastic graft to treat their injuries. And as you can see, the patency—now, it doesn't show up here, does it? It doesn't. Okay, so the patency number is about 91.5% at 30 days, and that compared well to 79% with synthetic grafts. But probably more importantly, the infection rate with our vessels was only about one-ninth the infection rate of synthetic grafts. This was not surprising to us based on what we knew about our product. And lastly, and most importantly, the risk of amputation was about one-fifth. So if you-- historically, if you were a patient who had an extremity wound, and you got a plastic graft to restore blood flow, you had about a 1 in 4 chance of having that limb amputated. In our case, if they got our vessel, you had a 1 in 20 chance of having your limb amputated. So these are the data that really provided the undergird of the BLA filing that went in in December. So as I mentioned, we filed in December. The BLA package was accepted by the FDA in February. As we let investors know in our May quarterly earnings call, we completed an inspection of our facility by the FDA in April, and we've been continuing to march through our interactions with the FDA, and we look forward with enthusiasm to our August tenth PDUFA date. I'm gonna talk a little bit about our second indication in dialysis access, and then I'll talk more about our commercialization plans. As I mentioned, Fresenius is one of our largest shareholders, and Fresenius is interested in Humacyte because we believe we're bringing to the table really the first important new form of dialysis access to treat kidney failure patients in many years. Dialysis is a complex business, but to boil it down very simply, if you have kidney failure and you need dialysis, you can have a catheter placed, a plastic catheter placed in your neck to pull blood out and clean your blood. Those catheters suffer a lot of infections and are very high cost and morbid for patients. You can get a plastic graft put into your arm that connects an artery and a vein, but plastic grafts also suffer from infectious complications and low success rates. Lastly, the gold standard is where a surgeon goes into your arm and sews an artery and a vein together to form a blood conduit that nurses can use for dialysis. That's called a fistula, and that fistula operation is only successful about 60% of the time. But that's the status of dialysis access. The gold standard only works 60% of the time. Meanwhile, there are more than 500,000 patients who are on dialysis in the U.S. right now. That number grows by a couple percent every year. Despite what you're hearing about the GLP-1 inhibitors, I don't think that dialysis is going away anytime very soon. So we have designed a trial that compares our Human Acellular Vessels, or HAV, to what is now the gold standard, which is sewing an artery and a vein together to form a fistula. We call that trial the V007 trial. That's a U.S.-only trial, and that trial completed enrollment last year. And in fact, we're expecting to get top-line results on that trial in the third quarter of this year. I'm gonna skip now to some of our commercialization plans because I wanna make sure that we leave a couple minutes for questions. Okay, so as I mentioned, Humacyte has a manufacturing capability and platform that allows us to grow tissues of different shapes and sizes. Right now, our clinical program, both phase two and phase three, includes trauma, dialysis access, and peripheral artery disease. However, we have active preclinical programs in pediatric heart disease, where we've done implants in juvenile primates and shown that our engineered vessels, smaller versions of the same thing that you've just seen, can help to restore function in a pediatric model of heart disease, congenital heart disease. We also have active studies underway in adult primates, well, where we're also using smaller versions of our vessel to do coronary artery bypass. And these experiments, we believe, will underlie an IND in coronary artery bypass surgery that we hope to file next year. In addition, we're using our HAV, as I mentioned, to deliver islets in a primate model as a potential therapy for type 1 diabetes. So Humacyte, even though that one vessel that we passed around the room here, you know, looks like a one-trick pony, we're absolutely not a one-trick pony, and for that vessel or for any other—for multiple other product candidates. So as far as bringing traumatic injury as our first indication to market, there are really a lot of advantages to launching as a small company, as a relatively small company, to launching ourselves in the US and the trauma market, and the reason are as follows: There's approximately 26,000 cases of traumatic injury in the US every year that require a conduit to repair them, but probably about 80% of those cases are clustered in a small number of medical centers. There's about 200 Level I trauma centers in the US, and most of those are clustered in major metropolitan areas. So for Humacyte, we're able to field a sales force of somewhat less than 20 sales representatives to be able to hit every single one of those Level I trauma centers throughout the U.S. So we'll be able to target a large fraction of the trauma market with a very reasonable-sized sales force. Also, importantly, for our follow-on indications in dialysis and peripheral artery disease. It's important to note that the surgeons that treat the trauma patients with the vascular injuries are the same surgeons that treat dialysis patients and patients with PAD. And so by giving exposure of these vascular surgeons to the product in the setting of trauma, we expect to be laying the groundwork for subsequent approvals and then market adoption. In addition, we've developed a budget impact model with our commercialization team that shows that even though the acquisition price of our HAV or engineered vessel, the acquisition price is certainly gonna be higher than it is for a plastic graft. By avoiding the large numbers of infections, limb complications, and amputations, we believe that we save the hospital money with each admission, particularly if they use our vessel instead of a plastic graft. And in addition, in the longer term, we also save insurers a tremendous amount of money because the cost of amputation is not just the tens of thousands of dollars it costs the hospital, it's also the long-term rehabilitation and the subsequent readmissions and the prosthetics, et cetera. So avoiding these costly complications by providing a conduit that's biological and immediately available, we think will not only dramatically improve clinical outcomes, but will also save the system money. So just, touching lastly on our manufacturing capability, Humacyte manufactures all of our products ourselves in our, in our facility in North Carolina. We, we've developed a proprietary cell bank, but also a proprietary manufacturing system, which is highly automated. And, these systems, which are incubators about the size of a school bus, we call LUNA200 units, and these LUNA200 units can generate about 1,000 vessels per year. We currently have 8 of these units installed in our building, but we have room for a total of 40, which means that, you know, in the long term, in the facility where we reside right now, we could make up to 40,000 vessels per year. We anticipate that this production ability will be more than sufficient in the early years of commercial ramp-up. And it also means that we've really de-risked the manufacturing scenarios because this commercial-scale manufacturing setup has been in place and has been used by Humacyte for our clinical trials since 2021. So it's not like we're transitioning to a new manufacturing system or facility, and there's risk there. That was de-risked several years ago. So we're very excited about the journey and about where we are right now. I believe that Humacyte is on the cusp of multiple, inflection points, multiple value-generating catalysts, both for our commercial story, but also for our clinical and our preclinical stories as well. I believe we're well-positioned in terms of having de-risked our regulatory path and also de-risked our manufacturing. The product has been studied again in hundreds of patients. We have a tremendous amount of experience with the product. We know that it works, and we know how it works, and we're very excited to bring it to the market in coming months. So I've, on purpose, left a couple of minutes for questions, and thank you for your attention. Can you just maybe talk about pricing? Yeah. So we haven't been explicit. We haven't given explicit guidance on pricing. If you look in some of our older SEC filings, we've provided estimates that the price point might be around $25,000 per vessel. When we have canvassed hospital administrators and payers about prices in that price point, either at that level or somewhat higher, we've seen little or no pushback on that price point because they understand the costs that are avoided from the complications that we believe we'll prevent. So is that, would you think $25,000 per procedure or per vessel? And could- It's per vessel. Per vessel. Usually, how many vessels would be used? Well, in a trauma patient, actually, it's typically one. In fact, trauma wounds are typically would use only a subset of what the vessel is that got passed around earlier. So the surgeons can trim it and have it be the correct size for whatever they need to do. Right. Maybe just if you can go back to that, was there a big difference between the results that you saw in the Ukraine trial and your overall results that you saw in your other clinical trial that you showed the combined? Yeah, there was only a small difference. The Ukraine results were actually a little better, even though the wounds, in many cases, were more horrific. I think that's because the Ukrainian patients were all young, healthy, military-aged males, and many of the patients that we treated in our US trial were elderly, and had a lot of concomitant disease, and so they just suffered more complications overall. But overall, the results are very similar.