All right, we're gonna move through, start the Monday afternoon medical devices track at the 44th Annual TD Cowen Health Care Conference with the Humacyte executive team. We're excited to have CEO and founder, Laura Niklason, and CFO, Dale Sander, here up in Boston. Laura, I'm gonna hand it over to you to take us through a presentation and update on the Humacyte story. Thanks so much.
Thank you, Josh. This is really great to be here. It's exciting to be in Boston at any time of year, but particularly during the TD Cowen Conference, which we've been to every year for the last several years. So I'm just gonna walk the audience through the general Humacyte story. Some of you may be familiar with it, but I'm sure many of you are not. Humacyte is really a company and a technology platform. We are a first-in-class tissue engineering technology. We use human cells to grow human tissues that are implantable into patients without any immune rejection. Importantly, we grow these tissues at commercial scale currently, and once the tissues are implanted, they repopulate with cells from the patient, and they become living autologous tissues.
Humacyte has made tremendous progress in advancing our first product candidate, which is the Human Acellular Vessel, or HAV, through various clinical and regulatory milestones. Importantly, we have completed a pivotal trial in using our engineered vessel to treat traumatic injury. This data formed the basis for a regulatory filing, a Biologics License Application, that we filed in December of 2023. Importantly, a few weeks ago, we got notice from the FDA that they've accepted the file, and they've even given us priority review, which means that we have a PDUFA date in early August. If the FDA approves the HAV for use in traumatic injury, we would expect to be on the market in September of this year. In addition, we have commercial-scale manufacturing for our engineered tissues already in place.
Humacyte has invested the time and the money it takes to take this revolutionary regenerative medicine technology all the way up to commercial scale. In fact, we've been using our commercial-scale systems and our facility to support our clinical trials since the middle of 2021. Here's the basis of Humacyte's technology. We use a human cell bank that Humacyte has isolated and that's proprietary to our company. Importantly, we have enough cells in our cell bank to support our commercial manufacturing operations for the next 30-40 years. When Humacyte sets out to make a batch of tissues, and currently, we grow 200 arteries at a time, we take a small vial of cells out of the freezer, and we thaw that, those cells out, and we grow them.
And then we seed them onto a scaffolding, and the polymer scaffolding that we use is the size and the shape of the tissue that we ultimately want to grow. After the cells attach to the scaffolding, we fill the bioreactor with culture medium, and we grow the cells for two months. During this time, while the cells are growing, they secrete matrix proteins, and all the while, that scaffolding is dissolving. At the final stage of the process, we then take this engineered human tissue that we've grown from scratch, and we wash the cells out of it. So what's left, the Human Acellular Vessel, and what gets implanted into the patient, is engineered human extracellular matrix proteins, proteins like collagen. Because these proteins are conserved amongst humans, the HAV can be implanted into any patient and not be rejected.
In fact, we've treated nearly 600 patients over more than a decade with a range of diseases, and we've never seen an episode of clinical rejection. In addition, because the HAV is non-living, it has a shelf life, and after we make a batch of vessels, we can screen them and then ship them to hospitals, where they can sit in the fridge for up to a year and a half until a surgeon or a patient needs them. Humacyte has taken our first product candidate, the Human Acellular Vessel, through multiple stages of clinical development. Our first product indication, which I mentioned earlier, is using the HAV to treat patients with traumatic vascular injury. The results from that pivotal trial read out last year and were the basis of our BLA filing.
But in addition, we've also completed enrollment on a phase III trial using the same HAV to treat patients who have kidney failure and who need access for hemodialysis. That trial was enrolled last year and will read out in the third quarter of this year. Thirdly, we have completed several phase II trials using the same engineered HAV to treat patients with critical limb ischemia who are facing potential amputation, but who don't have any vein to revascularize their limbs. Importantly, we're in long-term follow-up on two of those phase II trials, and a third phase III trial is just completing enrollment. That's an investigator-sponsored trial at the Mayo Clinic. I mentioned earlier that after the HAV is implanted, it repopulates with cells from the patient, and this is just an image of that shown here.
Cells in the wall of the HAV, which stain red in this image, are cells that came from the patient that migrated in from the outside of the HAV and took up residence inside the vessel. This is an active demonstration of how the HAV becomes a living artery. It becomes self over time. We believe that this repopulation provides two important features, which are really the hallmarks of the value proposition for the HAV. One is that the HAV resists infection after it's implanted. We've shown that this is due to its biological nature and the fact that it repopulates with cells from the patient and works well with their cells. Secondly, because cells repopulate the HAV, we believe that confers durability.
In fact, in some of our dialysis patients from our earliest phase II trials, some of those patients have used the HAV for dialysis for more than 10 years. So talking about our first indication, for which we filed the BLA in December of last year, this is really focused on the care and the treatment of patients with traumatic injury. Sorry for the gory photos, but as you can see, when a patient arrives in the emergency room, having suffered a gunshot wound or a car accident, or what have you, typically, if the vasculature is injured, these, these wounds are open, they're dirty, they're contaminated, and typically, there's no blood flow going down to the downstream tissues.
In the several hours that it takes to get the patient worked up and then finally into the operating room, it's typically been 2, 3, 4, 5, even 6 hours since the tissue downstream from the injury has had any blood flow. At that time, the surgeon in the operating room currently has 3 choices: He can go to another part of the body, which hasn't been injured, and injure that part of the body and spend an hour taking a vein out of the leg, tying off the branches, and then moving it over to the injury. That's option one, and that's considered the gold standard, although it delays revascularization for another hour. Alternatively, if the surgeon feels he doesn't have time, he can reach up onto the shelf and take a plastic graft down, made out of Teflon or Dacron.
But as you can imagine, when you put a piece of plastic into a contaminated wound, those grafts often fail due to infection. If the surgeon feels that neither of those two options are appropriate, then what he'll do is he'll amputate the limb. So that's the current state of play in the acute treatment of traumatic injury, and obviously, it's not ideal. One of the reasons that Humacyte focused with the HAV on trauma as its first indication, is because the characteristics of the HAV, the product profile, really address this problem. First off, the HAV is immediately available. It can. The surgeon can take it out of the fridge or off the shelf and can take it out of the bag and be sewing it into the patient within two minutes.
Secondly, as I mentioned earlier, the vessel repopulates with cells and becomes a living tissue over time, and for that reason, avoids the infections that can happen with a synthetic, like a plastic. So to provide supportive evidence in trauma, Humacyte conducted a single-arm pivotal study in 20 Level 1 trauma centers in the United States and 4 in Israel. In that study, which was a single-arm study, we would enroll patients who presented to the emergency room with all sorts of terrible injuries, and the patients would consent, and then they would have their injuries treated with the HAV. Because it was a single-arm trial, we worked with the FDA ahead of time to develop a comparator, a benchmark, against which the results in this trial would be judged.
That comparator, we agreed with the FDA, would be a literature review of how well synthetic grafts do when they're used to treat injured patients. For both the comparator and for the pivotal trial, there were three outcomes that were, that were the primary areas of focus. The key endpoint was patency or blood flow through the conduit at 30 days, and the second two key endpoints were resistance to infection at 30 days and also amputation. These are just some of the horrific injuries that were treated as part of this trial. We don't need to dwell on them, just to give you a sense of what was treated. I'm gonna skip this slide because I actually want to tell the second half of the story.
And the second half of the story on trauma has to do not with civilian injury, but actually with wartime injury. So while we were doing this single-arm trial in the U.S. and Israel, Russia invaded Ukraine, and during that time, shortly after the invasion, we started getting emails from surgeons in Ukraine asking for access to the HAV to treat their wounded warfighters. We obtained permission to send HAVs to 5 frontline hospitals in Ukraine, and during a year-long humanitarian period, we treated 19 patients with mostly wartime injuries. Most of these patients had either gunshot or shrapnel or blast injuries, and shown in this slide is an example of one of those patients, who suffered a horrific blast injury.
As you can see from the CAT scan image in the middle of this slide, the entire thigh is filled with shrapnel and debris, and some of that shrapnel pierced the femoral artery and cut off blood flow to the leg. This patient was treated with the HAV in what was obviously a contaminated wound bed, and although the surgeon said he actually thought this patient would not survive his injuries, you can see an image of him walking out of the hospital at day 113. So even though we had to train these surgeons over Zoom because we could not go to Ukraine and train them in person, the outcomes here were outstanding. Their patency rate in Ukraine was 94%, and we had 100% limb salvage and no infections.
When we informed the FDA about, at a high level, about how these data turned out, the FDA asked us to return to the Ukraine effort, gather as much data as we could on those patients, and then take that data and roll it into our civilian data to create a larger database containing both clinical trial and real-world wartime evidence. And so we did that, and here's the combined analysis of both those sets of results. What we find is that the patency rate for the HAV was 91.5%, which is substantially better than the 79% that we saw in our literature review, which served as our benchmark. In addition, the overall conduit infection rate was less than one-eighth of the literature benchmark, and the amputation rate was about one-fifth of the literature benchmark.
These outstanding clinical outcomes form the basis of the BLA filing that we submitted to the FDA in December. But we also believe that these decreased complication rates, which can be very expensive for the hospital and insurers, to say nothing if catastrophic for the patient, we believe that these savings and complications will really form the basis of, of a strong health economic argument to bring the HAV into the hospital and get it reimbursed, under current insurance systems. So, as far as, I've covered most of the points on this slide, but essentially, the FDA granted the, the HAV priority review because we, we have, we have an RMAT designation, a Regenerative Medicine Advanced Therapy designation, that was provided to us by the FDA last year for trauma.
In addition, several years ago, the Defense Department gave the HAV a priority designation, and said that it was one of the top 5 priorities for gaining FDA approval, because the Defense Department is very interested in having the HAV available in order to treat wounded warfighters. I'd like to touch quickly on our second indication, which is in hemodialysis access. So as I mentioned, we completed last year a phase III trial in hemodialysis access. This is a complicated field, and I'll try to very briefly summarize the requirements for hemodialysis access and what the product profile of the HAV means, particularly for patients with unmet needs. So if you need to go on dialysis because your kidneys have failed, you can have 3 ways that the dialysis center can gain access to your bloodstream.
You can have a catheter, a plastic catheter, which sits in your neck. Those catheters actually provide very inefficient dialysis, and they're very high risk for infection and sepsis. Alternatively, you can have a plastic graft that's sewn in between an artery and a vein, typically in your arm, but could be in your leg. Those grafts tend to have poor durability and also are very prone to infection. For all of these reasons, the gold standard in dialysis access is not to use plastic at all, but to take the patient's own artery and vein and sew them together. In doing that, the hope is that the vein downstream dilates up and becomes usable for dialysis over a period of months.
Unfortunately, about 40% of the time, more often in women than in men, but about overall, about 40% of the time, that operation doesn't work, which means that the vein never dilates up enough to become useful. In that case, the patient is stuck with a catheter in their neck for months or sometimes a year or longer while they're waiting for their gold standard fistula to actually become usable. So we believe that the HAV has the potential to not only improve outcomes, but also decrease costs of care, particularly for patients who are forced to remain on a catheter or have a plastic graft in their arm.
This comes primarily from the reduced cost due to infection, which can range from just IV antibiotics to hospitalization and death, but also because of the HAV's reliable usability for dialysis, which I'll touch on in a minute. But one of the key departures between the HAV and a fistula is that the HAV, four weeks after you implant it, is reliably usable for dialysis. It doesn't have to dilate, it doesn't have to mature. There's no waiting process that the physician has to do. In contrast with a fistula, as I mentioned, patients sometimes have to wait for months or longer.
So the reliable usability, combined with the resistance to infection, which is one of the reasons that fistula is the gold standard in the first place, we believe that the HAV can provide important benefits, particularly for patients who are at risk of having their fistulas fail. So we designed a phase III trial that we completed enrollment on last year. That was a prospective randomized trial that looked at the use of HAV versus a fistula in 240 patients at about 25 centers in the United States. This was a U.S. trial, and the primary outcomes for this trial are usability for dialysis and patency at 6 and 12 months. As I mentioned, we finished enrolling this trial last year, and we expect to have top-line results in the third quarter of this year.
These are not data from the trial, but these are just an indication of how this trial might go based upon what we already know. So in the purple bars here, with the yellow dotted line, are data that we've collected from different studies on the usability of the HAV for dialysis at different time points, going from one month and going out to five years.
We can combine that or put that next to the data in the gray bars, which are not from our clinical trials, the publications that report on fistula usability for dialysis at different time points.... As you can see, much of the benefit of the HAV accrues for the patient in the first 6 to 12 months, where if the HAV is usable after 4 weeks, that allows the catheter to come out and then cuts a tremendous amount of catheter exposure time and sepsis risk out of the patient's experience. I'll just touch very, very quickly on peripheral artery disease, and then I'll touch on our manufacturing and our commercialization plans, and also our catalysts for the next year.
Peripheral arterial disease, again, sorry for the gross photos, is a growing scourge in the United States due to our aging population, but also due to increased issues with obesity and diabetes. Even the GLP-1 inhibitors, while in the long term they will almost certainly cut down on obesity and diabetes, they will not make this problem go away. Last year in the U.S., there were about 160,000 procedures, surgical procedures, that were done to try to revascularize ischemic lower limbs, and many of those procedures were done for critical limb ischemia, in patients who either had no vein or had poor quality vein and who were at risk of amputation.
I'd like to just say, as far as the PAD experience, the data that we've collected so far and that we've published, we've published data at 2 years and at 6 years, has shown that our patients who've received the HAV in a setting of Critical Limb Ischemia without vein have shown a very low amputation rate. We have studies that are ongoing, actually one Phase 2 study at the Mayo Clinic, that we're just completing enrollment on the 30th patient right now, where investigators are treating patients who are facing potential amputation and who have no vein for revascularization.
Early reported results from the Mayo trial, when they compare their outcomes to what they've seen in patients who did have vein for operation and who did get vein use for bypass, what we've seen is that the HAV outcomes are actually similar to the vein outcomes. So, we're very excited to be designing a Phase 3 trial later this year that will really evaluate the impact of the HAV. Oh, that's my phone. I'm so sorry, assessing the value of the HAV in patients who have critical limb ischemia, facing potential amputation and who have no vein. So I'd like to just talk about our potential path to market and about the plans that we've made as far as rolling out our commercialization team and also our manufacturing infrastructure.
So as I mentioned, Humacyte's technology platform really is a platform. We can grow tissues in different shapes and sizes, and that will allow us ultimately to address a large number of markets. What I've talked to you about is the markets in the lower left-hand corner of this slide, which is traumatic injury, dialysis, and PAD. However, I can tell you that we've already done primate work and have published some of this work and presented some of this work using smaller versions of our vessel, both as a coronary bypass graft in primates, where we've presented results at the American Heart Association, and also using a smaller version of our vessel in a pediatric heart model of heart surgery, mimicking the reconstructive heart surgery that has to be done in infants with congenital heart disease.
That is a set of potential pipeline opportunities, where we would hope to be, certainly with the adult CABG program, we would hope to be in Phase 1 in the next couple of years. In addition, we're very excited about another program where we utilize the current HAV, which is the 40-centimeter long, 6-millimeter vessel, as a delivery vehicle to deliver pancreatic islets to treat patients with Type 1 diabetes. We've already published results on this concept, showing that we can reverse diabetes in a rodent model, and in fact, we're undertaking studies in larger animals, in primates right now, showing that we can maintain islet viability and maintain secretion of insulin long after implantation. So we're looking forward later this year to testing whether or not our biovascular pancreas concept can reverse diabetes in a large animal model.
So as far as the commercial launch in our first indication, which is using the HAV to treat traumatic injury, we're fortunate because Humacyte is gonna be able to do this launch ourselves. The traumatic injury market is a market that is actually highly contained. There's only about 200 Level 1 trauma centers in the United States, and most of these are in major metropolitan centers. This means that with a sales force of fewer than 20 representatives, we can reach essentially all the Level 1 trauma centers that treat the vast majority of these types of injuries. In addition, as part of our overall commercial strategy, launching in trauma, which is a very feasible sort of launch for a company of our size to initiate, also has a lot of feed forward into our subsequent AV indications.
That's because traumatic injury, but also dialysis access and peripheral artery disease, are all treated by the same surgeons. They're all treated by vascular surgeons... and there's only about 3,100 vascular surgeons in the United States, and about 96% of these people are in major metropolitan areas. So being able to target these same surgeons with the initial trauma launch and being able to get the HAV onto the shelf in the hospitals at the major centers, we predict will have a lot of feed-forward and positive impact into adoption of the HAV in later indications as we gain approval in dialysis and peripheral artery disease.
In addition, because of our priority designation, we would expect that after approval, we will negotiate with the Defense Department because we would expect them to purchase some quantity of HAVs as a stockpile to be able to bring forward to forward operating locations so that the HAV is ready should there be a mass casualty or an acute conflict situation. As far as working with hospitals and the value analysis committees to get the HAV on formulary once we're approved, Humacyte has already stood up a commercial team that's really focused on health economics and on market access. What we've developed is a budget impact model that clearly shows that by avoiding the complications that are associated with amputation, and infection, and prolonged ischemia time, that we decrease total costs to the hospital and also certainly to insurers by use of the HAV.
What's important here is that for traumatic injury, hospitals are reimbursed on a DRG or a fixed-price basis. This means that the costs of any complications, whether it's sepsis, or amputation, or limb necrosis, or gangrene, or prolonged ischemia, et cetera, but all of those complications essentially have to be eaten by the hospital. In this case, providing the HAV and avoiding those complications, even though the acquisition cost of the HAV is higher than it is for synthetic grafts, by avoiding these complications, we actually bring the total hospital costs down. Even more potently for insurers, for Medicare, but also for private pay, what we see is that the HAV will help those insurers avoid costs associated with rehabilitation, with prosthesis, and with all of the long-term care that has to go on with patients who suffer these complications.
For our second indication, which is in dialysis access, as many of you may know, Fresenius Medical Care is Humacyte's largest shareholder. They invested in Humacyte several years ago because they were very encouraged by the early data that we generated of the HAV in dialysis access. And as we gain our second indication in using the HAV for kidney failure patients, we would expect that Fresenius will enable and will facilitate bringing the HAV into hospitals and clinics and helping to adopt it as standard of care, particularly for those patients who are supported by our clinical trials and by our health economic modeling. As I mentioned, Humacyte has commercial-scale manufacturing in place.
We've been using our current manufacturing facilities to supply our clinical trials for 2.5 years, and we're very excited to have de-risked this part of the story. So, just in conclusion, Humacyte has been executing, I think, outstandingly well for the last several years. We've met all of the milestones that we said we were gonna meet, roughly when we said we were gonna meet them. We've de-risked the clinical story by having outstanding clinical outcomes in our pivotal trial and trauma. We've de-risked the regulatory story by filing our BLA and having it be accepted by the FDA with a priority approval pathway. We've de-risked manufacturing, transitioning to our commercial scale system 2.5 years ago, which I think is... I, I'm not sure I know of any other biologic where that's been the case.
Fourthly, we've de-risked our financial situation, because last week we were able to have a financing that brought another $40 million into the company and which we believe brings us to cash flow breakeven. So we're very excited about how 2024 is gonna unfold, and I look forward to sharing more news with you in the near future. Thank you very much.