Humacyte, Inc. (HUMA) Earnings Call Transcript & Summary

Good afternoon. I'm B.J. Scheessele, Chief Commercial Officer for Humacyte. Probably new to some of you. So actually, I thought I'd do a quick introduction of myself. Roughly 30 years in the health care industry, a biomedical engineer by training. And I've most of my career worked on building and leading successful sales and marketing teams, both domestically, then internationally, worked for Johnson & Johnson in the vascular space doing that, smaller companies like LifeCell in regenerative medicine, where I did compete against synthetics, poor performing synthetics similar to situation here. And this was obviously an opportunity to bring all that together, my vascular experience, regenerative medicine into one package. What I've been doing the last couple of years, in anticipation of this launch, building sales and marketing, health economics, market access, a lot of which we'll have an opportunity to cover today. Definitely appreciate you joining. We'll be a little bit in person and virtual given the weather and some of those challenges, but we were excited and wanted to make sure that we pulled this off today. So what I'll first do is introduce Laura Niklason. She's going to be virtual, dialing in here. She obviously is our Founder and CEO. She'll have an opportunity to walk a little bit through company and technology for those that aren't as well versed in it. I'll have an opportunity to then give you an update of where we stand early with our commercial launch. And then we have 2 surgeon speakers, experience with our product to talk about their use of Symvess, where they used it today, where they think it can be taken into the future and then an opportunity for Q&A on the back end. So with that, I'll turn it over to Laura.

Thank you, B.J. And yes, I'm sorry, I could not be there, tried to get in last night, tried to get in this morning, but the weather in New York was just not cooperating. So if we could just click ahead 2 slides. I'm not going to spend much time here because I think really the story is about our commercial launch, and you want to hear from our surgeons. But just at a very high level for folks who are not familiar with the Humacyte story. Humacyte, I'd like to say, is in the business of making spare parts for people. We have developed proprietary technology that uses human cells to make functional human tissues at a commercial scale. We manufacture these tissues in such a way that when they're implanted into any patient, they won't be rejected. And also, very importantly, after implantation, our engineered blood vessels repopulate with cells from the patient and they become a living artery over time. We believe that this repopulation confers durability and also a resistance to infection. And you're going to hear about some of those characteristics from the clinical cases from our surgeons. Next slide. So just at a very high level, Humacyte received our first FDA approval for using our engineered blood vessel, the ATEV, which is also called Symvess, trade name. We received this approval late in December of last year, and we announced official commercial launch just last week. Humacyte as a whole is addressing large markets. We are not a biotech company that's looking at little tiny orphan markets with 40 patients. We are looking at large markets in traumatic injury, both civilian and military. We're looking at dialysis access. We're looking at peripheral arterial disease. We control manufacturing. We do our own commercial scale manufacturing in-house, and we are located in North Carolina. So we believe that mitigates a tremendous amount of execution risk, and we have great partnerships with Fresenius Medical Care and with the Defense Department. Next slide. So at a very high level, as I mentioned, we use human cells to make our tissues. We use human vascular cells that we expand in the laboratory, and then we seed these cells onto a scaffold. It's a degradable polymer, and the size and the shape of the scaffold dictates the size and the shape of the vessel that we grow. The vessels that we grow are 42 centimeters long and 6 millimeters in diameter. And after the cells attached to the scaffold, they grow for a period of 2 months, during which time they also secrete matrix proteins, like collagen, and the scaffold is also dissolving. In a final step, we take the engineered artery that we've grown over 2 months and we wash the cells out of it. So the final product that gets delivered to the patient is an engineered human vascular tissue. It's mechanically very strong. It has a rupture strength over 3,000 millimeters of mercury, which is about 30x your blood pressure. It's mechanically very strong because it's nonliving, it has a shelf life, it can be stored for up to 1.5 years in the refrigerator, and it can be immediately available when surgeons and hospitals need it. Next slide. So for our approval in vascular trauma, we are currently approved for use in adults who require urgent revascularization to save a limb, and in cases where autologous vein or vein harvesting from the patient is not feasible in the eyes of the surgeon. Next slide. So the current state of trauma care now, both in the civilian and the military settings, is that when a patient presents with a traumatic injury and several hours later, is finally in the operating room getting a repair, the surgeon can either spend another hour harvesting vein from the patient and injuring him further or the surgeon can take a plastic graft off the shelf, which may become infected or he can amputate the limb. And that's prior to the approval of Symvess, that was really the range of possibilities available to surgeons and patients. Next slide. In our 2 single-arm trials that looked at both civilian populations in the U.S. and Israel and in a military population in Ukraine, what we showed is that compared to plastic grafts, which are the synthetic graft benchmark on the right in gray, what you can see is that the blood flow or patency levels of Symvess were substantially better than those reported for synthetic grafts. The infection rate was much lower, about 1/9 of the infection rate for synthetics. And probably most importantly, limb salvage was much better. So the 24% limb amputation rate with synthetic graft means that if you're a trauma patient and you were treated with a plastic graft, there's a 1 in 4 chance that you lose the limb. In our studies, that chance was reduced to 1 in 20. So we would argue that this is particularly important for patients, obviously, and surgeons, but also hospitals. And these data were really the basis of the approval for Symvess in arterial trauma. Next slide. Interestingly, we also did a retrospective comparison. This was not a head-to-head study, but we did a retrospective comparison of how well outcomes like patency and limb salvage and infection are with our vessel Symvess, as compared to vein. So to do this, we looked at a historical database of trauma victims called the PROOVIT database, and we propensity matched patients who were in the PROOVIT database, 2:1 to patients that we had already treated with Symvess. And as you can see from the numbers on this slide, our patency numbers for Symvess are a little bit lower than they are for vein. But if you look at infection rates and amputation and re-interventions, treatments for complications, we actually compare pretty well. So this is very encouraging data. We're hoping to publish these data soon. But this really provides an answer to surgeons because once we show surgeons that our vessel performs better than synthetic, the next question that they ask is, "Well, how do you perform compared to vein." And again, this is not a head-to-head comparison, but at least gives us a ballpark estimate that actually we do fairly well. Next slide. Okay. I'm going to turn it over to B.J. now because I think you've heard enough from me.

Thank you, Laura. So on the commercial side, I -- first, I would start with what -- how do we view the trauma market. And I'll take one step back that actually, we had to build this database, build our market understanding. When you think of trauma, there isn't just a lot of data there. That's not something that you can buy off-the-shelf. So we work with definitive health care, a leader in claims database to actually build this up. I think this was important for us, one, to know the size of the market, but also that targeting has actually helped us to know then where exactly to send our sales reps, which hospitals, which surgeons perform the procedures. So we look at it around 26,000 applicable market for a trauma vascular repair. That includes and really is focused on when you need an open surgical repair. That doesn't include, for instance, where it's a more simple, let's say, a patch or an endovascular-type repair. We're obviously focused on the open surgical. Our label is also on extremities. So it doesn't -- this 26,000 doesn't include torso and other type of injuries. But what it does also though include is iatrogenic cases. And I think these are highly underreported, underappreciated. So this would be where a surgeon is cutting out of cancer and, therefore, needs to cut vessels and repair them. It also includes where there could be a hip replacement being done and a surrounding vessel is lacerated. You obviously, in that case, your -- the surgeon is highly upset and having something readily available is important to them. Specific to the -- where we're looking to target in the market, we believe right now, and this is based off of that PROOVIT database, really definitive source of information that Laura had mentioned earlier, that it's about 75% -- 74% to 75% of the time, saphenous vein graft used and then synthetic and other type of products, the remainder of the time. Our initial target with our indication is on the synthetic and other. But we believe over time, label expansion, just general usage that we believe that we could capture roughly around half of this particular market. So a good portion of the synthetic other, but then also within saphenous vein, where saphenous vein not available, but also where they might use saphenous vein, but it's been such a time delay from getting that patient in that really the risk of a complication in amputation is significantly more that something off-the-shelf would be more amenable. Where we stand in kind of, in essence, the pillars of building for commercial and commercial launch, these 4 areas, we do believe a concentrated market back to that definitive health care database, understand exactly which hospitals, Level 1 trauma centers is the majority. But actually, we've also learned that there is some Level 2 centers that have a lot of volume that we had underappreciated and making sure that, that's within our targeting. Vascular surgeons performed the majority of these cases, but selectively trauma surgeons, who do have those vascular techniques, are also important targets for us, too. Our initial direct sales team is 10 sales reps. We would look to expand based on opportunity. They have a background in vascular and trauma regenerative medicine. They all have a performance of success, all President's Club winners, which basically means award winners from their previous companies. And then complementary to our commercial activities, there's medical affairs, medical education. I'm absolutely a big believer. You'll speak and hear from 2 of our surgeons. Peer-to-peer discussions are very important, not only in terms of how best to use the product, but how to best position it for not only current usage, but future usage. Market access is as it sounds, but also within that is our work with DOD. So now that we have approval, we've actually started to submit to the procurement and contracting vehicles, such as ECAT and SAC as part of working through our process. So we have begun that. On the right-hand side, I kind of -- when I talk to my team and surgeons and others, kind of think of it as kind of the science, the clinical and the health economic. You need all 3. Laura spoke to the science of how we make our product, the clinical data that she just showed with you, which is quite strong. I would also though say is that when we take our data out into the market, there really hasn't been any other studies done in trauma before. And so we stand apart actually having clinical data behind our product. And then there's the health economic side. Can you show that you reduce costly complications like infections and amputations that more than offset the initial acquisition price of our product. And to that point, and I can -- actually, excited to share that actually, just this morning, we actually had our budget impact model published. So Journal of Medical Economics, a peer-reviewed journal, validating the approach that we've taken here. Important because it benchmark off of our clinical studies, both the clinical data and health economic data that we collected in those studies showed that it more than offset the cost and use of our product versus synthetics versus these other products that we call, but those would be cryo veins, so the cryopreserved vein product and then the bovine carotid product. Again, amputations and infections, the majority of those cost savings. And I would say also though, we're very early in this launch, but you could well imagine some of the early questions we've had have been around the price of our product. I'm also happy to say that when we have the opportunity to walk surgeons or an administrator or even a payer through our budget impact model, and it's a dynamic model. We can actually sit down with a hospital or a payer put in their usage data, put in their complication data and the cost of complication and run that model. And then when we've had that opportunity, they have seen and been supportive of our price point given the clinical and health economic benefit that we can provide. I think also a part of when you think of health economics is and value is reimbursement. So we're working on and have applied for an NTAP, new technology add-on payment. So this is with CMS for Medicare patients. I'd also note that -- if you can get through CMS and with Medicare patients, Medicaid, TRICARE with the government and private payers, many times draft off of or leverage that work, and we'll pay if you can get through CMS. We've well along our way. We've not only submitted. We've had a successful town hall. We're actually in pretty regular communication with CMS and have learned that things continue to stay on track and not everyone can say that with every government agency right now. And if things continue to go well, it would be August time frame, we would hear back on that, that it is approved and then it's an October implementation. That goes with that what we've worked on previously is the ICD-10 PCS or procedure codes. That's how you track procedural usage, but that's important to have because that actually has to be in place and implemented for actually for that payment to take place the NTAP once it's implemented. And then the last piece I'll mention on my side is just a quick update of where we stand. So we've actually now, I guess, our press release...

The ICD/PCD codes have to be [indiscernible], where were they in terms of that...

No, they're completed. They're actually -- they're available to surgeons at this point. And they're only specific to us. They're actually unique to what we do. Others are actually aren't able to use them. So a quick update. With our press release, we were at 21. We're now to 26 VAC submissions, 2 have made it through and approved at this point. We're excited to say that, that typical is a 3- to 6-month process. The ones are a mix of those that we've submitted to are large institutions names that you know, some that were part of our clinical studies, some smaller institutions and larger institutions that we had no contact with before, but saw the value and said actually to submit. It's individual hospitals, but actually also hospitals that represent networks or collectives or IDNs and systems of hospitals. So if you're approved within one, it could actually be multiple hospitals. And then I would -- the last thing I would mention here, too, is that, yes, we were approved in December of last year. But it wasn't until just a little over a week ago that the FDA released and approved for sale of our commercial lot. So we're now just a little bit a week over. I think when we were doing some of our reconnaissance, there were plenty of hospitals that wanted to see that before finally pushing through. So now that we have that, and that's why we called it now the official commercial launch because we have all things ready and available to do so. And so we're eminently for sale any day now at this point as we have all this laid in place, and then that will ultimately have us off and running. So with that, actually, to introduce our first surgeon speaker, Dr. Mike Curi, Associate Professor of Surgery, Chief of Division of Vascular Surgery, just across the Hudson here, Rutgers new Jersey Medical School. And I'll turn it over to him and hear about his personal experience, probably has, so the most, if not the most experience, with Symvess as part of our V005 trauma clinical study.

Good afternoon. It's a pleasure to be here and talk about the product here that is truly something different for all of you who are imagining looking at companies that are putting out new technologies. This is a real big difference. This is not just a different stent. This is a whole different science. And for what it means for us is pretty impactful. So I'm a vascular surgeon. I run the vascular surgery program at Rutgers, which is in Newark, New Jersey. We have one of the busiest trauma centers in the country, with one of the highest penetrating injury rates in the country. So what that means is that we have a lot of vascular injuries. Believe it or not, some of the cases that I'm going to show here are not penetrating. This is actually a blunt injury where that's not considered penetrating injury. It wasn't a shot, a gunshot wound or a stab. It was actually a crush injury. And these crush injuries are really challenging. Somebody puts a hole in an artery, that's a pretty easy thing to fix because the bullet has gone through it or a knife has hit it, laceration. These injuries where there's a lot of soft tissue injury, they are the ones that get very complex. And when you think about what's the ability to salvage a limb, there's something called the mangled extremity score. And that's mostly for really high-impact injuries with large ballistics or crush injuries. So this first case is a leg that had a severe crush injury, as you can see with a lot of devitalized tissue, and there was an arterial injury. So while the bones needed to be repaired, the soft tissue needed to be healed or replaced, the only way this patient was going to keep that leg was to replace or reconstruct the artery that was damaged. And in this one, there was about a 10-centimeter gap after getting down to the artery and then taking away all the devitalized part of it, left a decent-sized gap, not something we could bring the ends together, so we got to reconstruct it. Then you got to think about, well, am I going to go get some vein out of the other leg. You can't use the vein on the same leg. Most of the time, the vein is also damaged on this side. So you don't want to take the superficial vein, which is the alternative pathway for the blood to get out of the leg. If the deep veins are already injured, you don't want to take the saphenous vein from the same leg. So the other leg, not really available to us or in many of these cases, it's been close to that 6-hour mark where the patient had a prolonged ischemia. The damage done to the tissue beyond what's actually injured from the ischemia, from the lack of blood flow, there's a ticking clock. And typically, we think somebody at the 6-hour mark is at their limit of what they could tolerate. And so as we get more complex injuries and the workup is longer or if there's prolonged extraction from the vehicles or whatever, then we wind up bumping up against that time and going and spending 45 minutes to an hour getting vein out of the other leg makes it difficult, the additional issues of having to prep the other leg and making the actual operation work. Plus you're creating wounds on the other leg. So in this case, we did an interposition graft with the Symvess from the popliteal artery, which is just at about the knee to the tibioperoneal trunk, which is below, it's a smaller vessel. And these reconstructions are more challenged for long-term patency than larger arteries. And this turned out really well. This patient was able to save the leg. Prolonged time in the hospital after the repair, lots of other surgery for the bone, for the plastic surgeons to come in and try to cover things, and patient did really well. This is another crush injury where this patient was actually crushed between -- actually at the port of New Jersey, New York and Elizabeth and a large crane crushed her up against a boxcar. And you can see the amount of tissue damage here, where there's -- all of this all is basically affected. You can see all the clean plane lines. This is the artery on the other side. The artery here is no longer has any blood flow in it. And so there's air, these black pockets are air, which means that that's a high risk of infection. And you can see the clean artery and vein on this side is not there on the other side. So this patient required a significant amount of soft tissue reconstruction and debridement, taking out a lot of dead tissue. And we were able to use the Symvess to reconstruct her artery. She was in the hospital for months. You can see here, this little pocket here is basically a pocket of pus, and that's a graft right next to it. This is what we're definitely afraid of as surgeons when we're putting in a piece of, we call it, plastic, but usually, it's GORE-TEX or Dacron, which is polyester. And if you have a piece of GORE-TEX in there, your heart drops when you see something like that, and you know that it's not going to last. And this is incredible how this patient has done amazingly well. She's a couple of years out, like nothing's happened. So this is the third case. This is a more straightforward gunshot wound to the upper thigh, and you could see here, that's the femoral head on the right side, on the left side, basically the proximal superficial femoral artery had a bullet go through it. The vein was also transected, required ligation. It's harder to repair and replace veins. They don't tolerate that well. So typically, they get tied off. So using her vein on that side was not an option, and she was beyond the 6 hour mark. And so we spoke to her, and she was okay enrolling in the trial. And you can see the replacement vessel is actually this portion from here to here. So it's about a 4-centimeter, 3.5-centimeter piece. And to make an incision on the other leg and go chase that vein on the other leg to do that is a whole different type of operation than being able to open up a package and use that at 2:00 in the morning. She did really well. She's a couple of years out as well. And then this was actually -- I believe this might have been the very first case in the United States. This is a patient who had a pretty bad fracture of the bone. You can see it here. You would think that, that was like a high-velocity car accident. He's actually a skateboarder. He had an open door swung open up from a car while he was on a skateboard. I don't know he must have been going really fast. But yes, a skateboarding incident wound up being the first patient enrolled in the clinical trial for replacing an artery with a grown blood vessel. And this patient is now 4 years out, doing great. There's an interposition graft, you can see it. It looks like tissue. It's just a lot cleaner obviously, looking than the other stuff. But if that are -- if that vessel had not been in a field where there was a tremendous amount of bleeding, that's what that vessel would look like. It's just that there's so much hematoma and bleeding in there, and this artery actually has a bunch of blood in its wall. But that's kind of like what a real artery looks like if you do in a clean dissection. So it really works quite well. It acts a lot like normal artery and a lot better than what we have from a standpoint of what's available from a prosthetic standpoint at this point.

We'll have some time for Q&A at the end. So Dr. Siada, are you on? Excellent. So Assistant Clinical Professor, University of California, San Francisco, will speak to not only his experience with Symvess, it was actually an expanded access case, so he'll walk you through that. But his hospital was actually also the first one to approve the VAC approval to bring Symvess into his institution.

All right. Can you hear and see me okay? Okay. Great. So my name is Sammy Siada. I'm a vascular surgeon in Fresno, California. The hospital I work at has a level 1 trauma center. It's the busiest trauma center in California by volume and the third busiest emergency department in the state. So we see tons of trauma, but with that, we also see tons of peripheral artery disease and a wide variety of vascular conditions. Next slide, please. So this was an expanded access case. This is a patient of mine, I've been following for a few years. I had treated her right leg. She was kind of lost to me for a couple of years, and she came back with a new blister on her left half, close to her ankle. She's diabetic. She has a high blood pressure. She has known peripheral artery disease. Interestingly, somebody thought it was a good idea to do a saphenous vein ablation on her for varicose veins. Obviously, you can see this wound. It's pretty ugly. It was infected when I saw it, I put her on some antibiotics. And one of the surest way to assess limb perfusion is to obtain a blood pressure of the toe, the great toe is kind of what we use typically. And she had no detectable blood pressure in her great toe, indicating pretty severe ischemia or lack of blood flow to her foot. Next slide, please. So with that, I took her to the cath lab to do a diagnostic angiogram, and this basically is shooting die down the leg to obtain a road map of the blood flow. Now the images on the right hand are the left leg. Obviously, the kind of the reference there is the right leg. So go ahead and click again, please. So you can see here, first of all, there's a narrowing of the common femoral artery in the groin. And furthermore, you can see a little wisp of the superficial femoral artery, but that bracket indicates where the superficial femoral artery is normally supposed to be. Here, you can't see it light up whatsoever because it's completely occluded. The big branch going off to the right is the profunda femoris, that's the deep femoral artery. And then click again, please. And then this is below the knee. You see the popliteal artery come back. And if you could click one more time. The anterior tibial artery is the only blood vessel supplying her foot. And that popliteal artery appears relatively healthy. And so we need a solution to revascularize the patient in order to salvage her limb. Next slide, please. So my decision-making in this case was, well, first, she doesn't have any saphenous vein. For a long segment occlusion that starts in her groin and goes all the way to her knee, the best option usually is a bypass. So if the patient has a good saphenous vein, that would have been a no-brainer solution. But unfortunately, she had both of her saphenous ablated. In this case, an endovascular treatment was not ideal, a, because of the length of the occlusion. It could have been attempted, but she also had that stenosis, the narrowing in her common femoral artery. And so that was prohibitively risky, in my opinion, especially that she had a large wound. I wanted something that would have a pretty good patency. So I really felt that a bypass was the best option for her. Now this wound was in a location that was close to where my incision would be for a bypass. So I did not want to use PTFE or GORE-TEX or plastic because it's really close to this infected wound. And furthermore, the patency isn't really that great with plastic anyway. Another alternative is cryopreserved saphenous vein, which is a cadaver vein. That's another alternative. The issue with that is the patency on cryopreserved conduits is abysmally low, and they are not very durable, they have a tendency to fall apart. So those are -- those have kind of fallen by the wayside. Another alternative is Dacron or a woven graft. That's also not preferable in an area that has a high risk of infection. So fortunately, I had some experience in the past with the ATEV when I was a fellow and strong believer in the technology, and it was nearing FDA approval, so was able to team up with the Humacyte folks and my hospital and the FDA to obtain emergency use authorization. And so click the next slide, please. So basically, the strategy is to do a bypass and that's basically rerouting the blood flow around the blockage, and this is kind of a nice schematic showing you there. That's obviously a vein. We didn't have vein. So I use the ATEV, click again, please. So here, you can see me, I sewed the artery to the common femoral artery. So I opened the artery, I cleaned out that narrowed segment and I sewed the graft onto the common thermal artery. Click one more time. And I had to sew 2 pieces of the ATEV for it to have an adequate length to reach the below knee popliteal artery. Next slide, please. She did very well. She went home postoperative day 2, which is pretty remarkable. Saphenous vein, even though it's a very durable conduit, it's fairly morbid to take it out. I mean, we'll still take it out if the patient has it, but it requires multiple incisions along the thigh. Usually, the patients end up staying in the hospital for at least 3 to 5 days. In this case, since the patient didn't have a saphenous vein harvest, she had 2 small incisions, one in the groin, one below the knee. She was able to go home the second postoperative day. And when she followed up in my office, initially, she had no detectable blood pressure in her toe, her great toe pressure was 130 millimeters of mercury, which is a remarkable improvement considering where she started. Her wound, we watched her wound very closely and it healed within weeks, and it's been about 6 months since her surgery, and I follow her with ultrasound surveillance, and her bypass is widely patent. She has no issues, no symptoms. And then on the right side, those are just some Doppler waveforms indicating kind of the blood flow in various areas in her foot. So she had a really positive outcome. Next slide, please. So with that experience, good result. I approach the hospital to get this approved not just for trauma, but just -- obviously, it's an FDA indicated for trauma, we're going to get it on the shelf for vascular trauma given that we're such a busy trauma center. I think there is definitely an unmet need in the trauma population, in patients who don't have saphenous vein or they have multi-organ trauma, there's a lot of indications for that. I think long term, there are far greater peripheral artery disease patients than there are vascular trauma patients. And we are in need of an alternative conduit besides autologous vein because very often autologous vein is not available, and the alternative conduits that currently exists on the market are suboptimal, whether it's the cryopreserved allografts or the kind of the plastic, the GORE-TEX, the GORE-TEX graft. Those are -- those tend to be -- have a high infection rate relative to an autologous conduit, and their patency importantly is very poor. So that was the rationale of the hospital that I gave the hospital. And so luckily, I have a very good relationship with the value analysis committee. Their sole question was how often it's going to be used because of the cost. I mean, that's kind of the -- at this point in time, that's kind of the limitation of its widespread use is the cost. And so my -- what I told them is it would probably be used a few times a year, at least to start. It only comes in one size and one diameter in one length. Over time, as the technology evolves and more sizes and lengths come out, I can only see it being used even more as we have more data about patency, comparing to autologous vein and comparing it to alternative conduits like plastic and cryopreserved, I think that the use of this conduit is only going to expand over time. So with that, happy to take any questions or comments.

[indiscernible] will be available, obviously, Laura, Dr. Siada online. While we just quickly set up, I thought, I would -- I can pass along and around. So this is actually the Symvess, the ATEV. So we grow them within these bioreactor bags. So as Laura described, seed it with a donated human aortic smooth muscle cells, feed it the media, grow it into a vascular structure and tubular structure, decellularize it, so it's universally implantable. And so Dr. Curi, Dr. Siada would just take this off the shelf, cut it open. The white piece in the middle there is the vessel itself and then be able to immediately implant it. It doesn't require washing off, doesn't require rehydration. And what we talked about time is such the essence. But again, just readily available off the shelf, but I'll pass it around. And we can open it up for questions for the surgeons, for Laura, for Dale, Dale Sander, our CFO, Corporate Development Officers here and myself, please.

Yes, I'm just curious if you had -- you've had good results with the pictures you've shown us with the patients, and you said they all recovered. I'm just wondering, has it worked for everything that you've been involved in? Or the patient was this too far gone in terms of the injury? I'm trying to get a percent of how this works.

That's a great question. So in trauma, I spoke about the mangled extremity score a little earlier. And sometimes we push our boundaries and the effort to try to save a limb that may or may not really truly be salvageable. So we had -- at our institution, we had one case where the patient losses limb, the actual bypass was still open. That's a failure of our therapy, not a failure of this graft. This is -- the patient's limb was just too mangled. And then I had one of these grafts that was used to save someone's limb. And unfortunately, he was a really challenged patient, wasn't taking any of his medications, and he came back and the graft was actually thrombosed, and this was about a year, 1.5 years after he was walking around with a great result. But he had some psychiatric issues and wasn't following up appropriately and came back and the graft was thrombosed, and one of my partners actually did a standard therapy to open it back up, and it opened up and the graft was doing great. But because he had such a long time with no blood flow down to his leg, he lost his foot. At the time of the amputation, the bypass is still running wide open, which was very helpful because otherwise, you wouldn't have healed the amputation, but he -- that was not an issue from my perspective, that was graft related. Those are the 2 that we've had issues with.

If you don't mind, I'd like to ask a question. I found it fascinating that Dr. Siada talked about PAD. And I don't think the Street, Wall Street has really factored PAD in, at least not at these valuation levels. What's it going to take for us to see use in PAD prior to results of a clinical trial? Will we see vascular surgeons going in that direction now based on your experience?

So when we have a tool available to us as surgeons, oftentimes, they've been -- whatever tool it be, may be a stent, a graft, whatever it may be, has an FDA indication. And I mean, you guys probably could do an analysis of lots of other devices that are out there of what their on-label indication use is versus the total use. I just think about an aortic stent graft that is supposed to have a 2-centimeter neck to put that stent graft in there by FDA indications. That probably is maybe half of what aortic stent grafts are being used today. And I mean 50%, I would guess, 40% to 50% are being used outside of its FDA indications. Once this becomes available, just like Dr. Siada said, I mean, we don't have good options when the patient has no saphenous vein. They're just really not any great options. That's a really standard case. And none of us like to use the prosthetic grafts in those. And we reach for these cryopreserved veins, and they just don't work well.

Does this ultimately obsolete saphenous harvesting? I mean it just seems like it should, right?

I'll let you answer, then we will have Dr. Siada jump in, too. Go ahead.

Yes. So I think that remains to be seen. Okay. I think -- I mean, for me, very data-driven. There's got to be some data to show me that this is equivalent to make me not do the extra work to get the vein out for my patient. There are a lot of surgeons who are going to be like, that's a lot easier operation. I think they're about equivalent. Let's go. And that is reality of the world. But I think that, and me as a researcher, I look forward to the opportunity of putting this graft up and kind of comparing it and seeing what happens. Even if it doesn't work as well as saphenous vein, if it's a lot better than the PTFE, which I'm pretty convinced it is, I think there's going to be a significant amount of use in PAD. And then -- and it's amazing how often we don't have saphenous vein. He mentioned something that's amazing that he said is that he couldn't believe that somebody had burned her vein, ablated it. That's one of these other technologies that I don't know if any of you have been involved in commercializing or putting out there. But that's a technology that is completely overused, and there's a lot of money in that business of sclerosing veins, and there was a lot of veins that don't need to be sclerosed, and they wind up -- there's a lot of patients that don't have vein because of it. And it's just getting more and more.

Dr. Siada, please jump in.

Yes. I agree with everything Dr. Curi said. Saphenous vein remains king right now. And so until there is high-level data to demonstrate its equivalents or non-inferiority, that's when we're going to see wide use. But that's not -- I mean, that's an aspirational goal, but we don't even need for it to be that good for it to be -- have a widespread use in the PAD population. There are tons of patients that don't have saphenous vein. And so really the long-term question that I have is what is the patency and how does that compare? The patency and the trauma population is pretty good, but trauma patients otherwise have healthy vessels. PAD patients have diseased vessels. And so when you do a bypass, there's several different bypasses you can do. You can do it to the above knee, below the knee, tibial, to the foot, and we're going to need patency data on all those things. For example, a femoral to popliteal artery bypass above the knee has very good patency with plastic. It's not as good as vein, but it's pretty good. I agree in the sense that Humacyte or the ATEV is going to be -- I think it is better than PTFE. And there's a lot of people who do a lot of PTFE bypasses. So I think there's a role there. Ultimately, I think the majority of surgeons are guided by what they feel is the best thing for their patient. And the case that I presented, I felt like the ATEV was the best option, given the entire circumstances. Do I have strong Level 1 data to prove it? Not yet, but I felt in my heart of hearts that that was the best solution for the patient, and that's why I fought for it hard and went through the whole FDA process to get it approved for the patient. So I definitely think there is a role going forward. The technology is fascinating and very convincing. So I think -- and most of my partners in my group of 7 surgeons, I mean, we agree with it. I mean the -- we believe in the technology. Ultimately, how widespread its use is going to be, is going to be dictated by long-term patency data.

I don't realize, but you're on a split screen right now, and I can see Laura right next to you. So I'd ask Laura, help me understand what's Humacyte doing to empower Dr. Siada, so that we can see this kind of going mainstream.

Well, I think Humacyte, as a company, of course, we have a huge belief in other market opportunities, including dialysis access, where we've put a ton of investment into Phase III trials and where we think we're going to get our second indication. I actually -- we haven't talked about dialysis access, but I think there are important groups of patients who will benefit enormously once we get approval there. And the same with PAD. We've supported 3 Phase II trials in PAD, all in patients who did not have vein, all in patients with critical limb ischemia or chronic rest pain. And the limb salvage data from those trials is outstanding, including one that's recently been published sort of in process out of the Mayo Clinic. So we strongly believe that there are a lot of patients who can be helped by this. Obviously, Humacyte would never market to off-label indications. That's not what we would do. But certainly, on my to-do list is once we do have approval, is to help support investigator-sponsored studies that want to look at some of these other indications so that we can help build out the data set in addition to working on our own Phase III prospective study. But I think having additional data from surgeons in the community actually using the vessel, now that we are approved, will be vital for expanding our knowledge on how many patients we can help.

I would just say one -- add on to that is, one of the other things that you're asking about is how do we -- how does it wind up getting used for these other things? I think once a surgeon touches it, it's one of these things that it's so different than anything else that we have. It feels so normal, so much like the human body. It's just one of those visceral responses. And when I think about what is on our shelves in a trauma center, we'll use it a couple of times a year in a trauma. There's no doubt it will be used at least as many times for either what was already presented that kind of bypass or the patient who comes with an infected AV graft or an AV fistula. We've been involved in those AV access, arterial venous access for dialysis patients, and we've seen it from really well in those situations.

This is Kristen Kluska, at Cantor. One question for the company and one question for our surgeon guests today. First, to the Humacyte team, it was nice to see that some of the centers that started VAC process don't actually have any experience yet with the product. Can you talk about how they became aware, what drove their interest, especially right out of the gate with the approval and launch? And how you think their uptake could look versus the centers that already have some experience under their belts.

Yes, I can take that one. And then I guess the next question will be for you guys. Yes. I mean, once we had approval back in December, we were able to go out and start to seed the market, speak to not only our labeled indication, the data that supported that the health economic messaging behind it. And then it's also, frankly, just a really good sales force that has relationships, relationships in places and institutions that weren't part of our clinical study. So I think it's connection, it's the hard work, it's the messaging, but also the relationships. And it's interesting. I mean, I think some of them could be as has as much, if not more volume than some of the places that you know. I mean that's kind of what's been interesting and exciting that as we dug into that definitive health care database and understand volume, there are some places, Level 2 and others that do a lot of cases, not a lot of people know about, but we've identified them and now are working to capture them. So it's one of those you kind of don't assume just because it's a big name or a small name, volume can be deceiving. And we're being very obviously, data and analytical and fact-based and making sure that we go after the ones with the most volume. So the second question was for surgeons?

Yes, thanks for the 2 surgeons. Maybe can you speak about the comment about the VAC and the question regarding how often would you use it? Is there any chance these conversations could change, should you find that you're using it more than you anticipated? And then also, how might real-world evidence and experience help with conversations moving forward, especially if this product is used in other indications down the line.

Sam, you already spoke about this.

So luckily, in my hospital, we had already trialed it. We had an emergency use authorization. So the hospital sawn its utility immediately with a good patient outcome. Hospitals tend to want to be on the forefront of technology because they want to be able to market that, say, "Hey, we have the latest and the greatest." So if you have buy-in from the surgeons, what follows from that is buy-in from the hospital. And so to convince the hospital that we should have it wasn't very difficult conversation. The one limit is the cost. And so the hospitals get abundant payment per procedure. And when you have a device that's pretty pricey, and sometimes you're using 2 pieces, that can be an obstacle. That being said, once the new technology add-on payment comes through, I think that will make that conversation even easier with the hospital. And as time goes on and technology matures, costs and prices go down. So I think the sky is the limit really long term because there is a clear need, at least from a vascular surgeons perspective, for an alternative conduit. And so I don't think it's going to be difficult to persuade surgeons that there is a role for this graft. And so once you have that, I think the hospital also will follow suit.

Specific to your question about will all hospital come back and say, limit its use because of its -- if you're using it more than what you say, if on the VAC application, they ask you how many times you're going to use a year and you would say, "We'll use it 12 times a year." And then in the first 2 months, it's already 10x. Are they going to come back and tell us, we can't use it? I've never been in that situation in 20 years of practice. I've run a VAC both at my university hospital, which is a state run hospital, takes care of a lot of underserved people. But I also, I'm on the leadership integration group for our health system, and we have a private community hospital that is part of a 15 hospital system. And we're getting -- we're putting it through the VAC at that hospital, it's actually in Jersey City. And once it's approved there, it's approved in the system. Whether those other hospitals then stock, it is up to whether the surgeons at those hospitals say we want to have this, but it's already approved for use. And that usually comes to in our system, the leadership group, which is like the heads of vascular across the different hospitals, and it's usually made a decision whether or not it's allowed.

Josh Jennings, from TD Cowen. Just follow-up on the VAC approval process. It sounds like at the University of California, San Francisco, it was smooth sailing. And maybe you could just help us not just for the decision to adopt or get the VAC committee through the adoption decision on Symvess, but also for other technologies. I mean what is held -- what is at the top of list the boxes you check, I mean, my understanding for Symvess and vascular trauma, clinical data is there, cost-effectiveness is there. But maybe you can just help us think about, why it was so smooth or just more details on why it was so smooth at University of San Francisco and then maybe over in New Jersey, what's the path forward there with the VAC approval process?

So for the record, I'm not at UCSF Hospital. My hospital is called Community Regional Medical Center. So it's affiliated with the UCSF, but it's not a UCSF Hospital. But to answer your question, really, there's a clinical need for it. And I think that's number one. If there's a clinical need, a quaternary level hospital is going to want to be able to provide that comprehensive care. And so if you can make that case to the VAC committee, they're usually -- that's why it was so smooth. And I had a case example that didn't really -- that didn't cost the hospital anything, and they saw the clinical need. And they tend to get excited about these new technologies that come out, especially when they see it benefiting somebody in the community, they can use that as a marketing tool. And so I found that to be probably the main reason why it was very smooth. We had no obstacles. And they asked me how many times are you going to use it a year? I said, probably a handful to start, and we'll see. This is not something we're going to be using every single day, every single week. If that was the case, it probably would have been a different conversation, at least until the new technology add-on payment comes through.

And I would say that there are 2 things that get priority in the VAC analysis. One is, are there substitutes available? And in this case, there's really not, right? It's a different biology. It's a different technology. And I think that can be -- that argument can be made. It's not just another stent graft to treat, and we've got 5 different aortic stent grafts, right, or 12 different balloons. We just need to add on a 13th balloon. This is unique -- so the uniqueness of the product. But then the other thing is that I think is helpful in VAC is when things are used in an emergency basis, it's a different concept of how you look at things compared to stuff that's elective. And hospitals get nervous when they can't take care of a patient with an emergency condition that would otherwise be treatable. And I think this is -- for trauma-related stuff, it's really rare that we've ever really said, no trauma surgeons, you don't get this, unless it's just another thing that is like add-on to multiple others.

And then just a follow-up on your download about the -- just the visceral reaction, maybe an aha! moment for vascular surgeon when you just first feel the ATEV in your hands, maybe for both surgeons. Just maybe expand on that and just the handling. I know you demonstrated a case out at West about where you had end-to-end anastomosis 2 ATEVs together for that bypass surgery. Maybe just talk about the handling, and we build out more about why it's such a visceral aha! moment for vascular surgeons when they first handle it.

So when we take another graft out of a box, it's usually a relatively stiff material that doesn't feel like human tissue. And when you sew it, there's compliance mismatch that is like it's just palpable. You can feel the difference. There -- so when you feel it, it feels like the tissue rather than a some foreign or mechanical piece. When the suture goes through it, it goes through it as if it's a healthy vessel. And that -- the way you pull the suture through, it feels normal.

Yes, I agree. I think tissue handling is -- it works really nice. The challenge is the size mismatch, if you're going distal to smaller arteries. But I think technical success with the graft is going to be close to 100%. I think if you're selecting the right patient, handling it and actually getting a technically sound bypass done, I don't think it's going to be any issue. It's very easy to handle, very easy to use. And over time, hopefully, we'll have longer grafts, and I anticipate that we were going to have a greater selection and that's only going to make it easier down the road.

So I think we're bumping up on time. Maybe last question, go ahead.

Yes. You actually kind of just touched on it, but I was curious outside of the clinical data aspect, what would be the driving factors that would increase your adoption. And it sounds like it's going to be different sizes and whatnot. But if you guys could just speak on that a little bit more.

Yes. If it's available in different sizes and lengths that's going to be helpful. Once you're below the knee, the vessels are smaller. And then obviously, in the belly, the vessels are bigger. So there are places where you can expand its use by having different sizes. The length sewing 2 together is a lot easier than going and getting vein out of somebody's arm, which is like the alternative, which isn't done a lot, but we still do it. If they don't have vein in their legs, we go chasing 3 different pieces. I mean, there are patients who have had all 4 veins in the arms kind of sew it together, wrote a paper back in around 2,000 about using arm veins, composites grafts. But yes, so that will be nice to be able to have various sizes.

We also think the ultimate kind of dictator of what -- how widespread is going to be the long-term patency. If I never have to harvest the saphenous vein, again, I would love that. But unfortunately, nothing rivals the saphenous vein. And so I'm going to keep harvesting it as long as that's the best option. But ultimately, once we understand there is preliminary data coming out, once we see its comparison to saphenous vein and prosthetic graft over time, that's going to kind of dictate how -- let's say, it's equal to saphenous vein, then why I ever harvest saphenous vein again if it's the same. I would much rather use a conduit that rivals that patency without having to fillet the whole patient's leg open and keep them in the hospital for an extra couple of days for pain control. But that's obviously a lofty goal. That's not the -- I mean, you don't need to -- you don't need it to be that good for it to have widespread use. It's probably -- I predict this is going to be better than GORE-TEX and plastic. That alone will expand its use to patients who don't have adequate saphenous vein, which is a large contingent of PAD patients.

Patients with saphenous vein, and you've got a 3 -- and I'm sure Sam's going to back me up on this. You got a 3-centimeter or 5-centimeter defect in a femoral artery. If this is available, I'm not -- I'm just -- it's unlikely I'm going to be going in and chasing vein in 2:00 in the morning. It's just -- because I know that, that conduit is not a challenge. The only reason I don't use the prosthetic in those situations is because the bullet has gone through there, and I worry about infection. And rather than getting the saphenous vein out of the other leg for those short pieces, it's still got to use a whole 40-centimeter piece, but I'm going to take that and cut my 3 piece, 3-centimeter, 5-centimeter piece and use it.

Great. I was going to say, Laura, any final words?

No. It's just -- I've spent so many years in the operating room with surgeons and -- but every time I listen to you guys, I learn more and more. So I just really appreciate your time. Thanks so much.

Thank you, guys, for joining.