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

Good morning, and welcome to the Humacyte Virtual KOL event. [Operator Instructions] As a reminder, this call is being recorded, and a replay will be made available on the Humacyte website following the conclusion of the event. I'd now like to turn the call over to Dr. Laura Niklason, Founder, President and Chief Executive Officer of Humacyte. Please go ahead, Laura.

Thank you, Tara, and thank you, everyone, for joining us this morning for our virtual KOL event, describing the use of Humacyte's acellular engineered tissue engineered vessel for arteriovenous dialysis -- for arteriovenous access in hemodialysis. Next slide. This morning, we're very fortunate to have 3 speakers with us. We have Dr. Timmy Lee, who is the Vice Chair for Research at the Department of Medicine at the University of Alabama, Birmingham. He's a noted nephrologist and also an expert in some of the challenges of dialysis access for kidney failure patients. Secondly, we have Dr. Hussain, who's a vascular and an endovascular surgeon at the Brigham and Women's Hospital. As a vascular surgeon, he has participated in the V007 clinical trial, and in fact, he presented our top line results at the American Society of Nephrology just a few days ago in San Diego. And thirdly, we have Dr. Keith Ozaki. He's also a professor of surgery at the Brigham and Women's Hospital. Dr. Ozaki has participated in several of our clinical trials, and he will be presenting a specific case report of a patient who would have benefited from Humacyte's ATEV had it been available for her care. So really the objectives of this webinar are three. First, we want to understand and explore some of the gaps in the care and management of hemodialysis access, particularly for certain subgroups of patients who are -- who have kidney failure. Secondly, we want to present an overview of the data from the V007 clinical trial, which compared Humacyte's ATEV to the gold standard, which is arteriovenous fistula in patients who are on hemodialysis for their kidney failure. And lastly, as I mentioned, Dr. Ozaki will present a real-world case of a patient who really struggled with her access and provide some thoughts and commentary on how newer conduits may have helped this patient. And with this, I'll turn it over to Dr. Timmy Lee. Thank you very much.

Thank you so much. I appreciate the opportunity to discuss current gaps in AV access. So these are the slides that I'll be discussing this topic. So I am a clinical nephrologist. I do research in this area, but hemodialysis and hemodialysis patients and access is something that I see every single day. So just a little bit of background. When a patient reaches end-stage kidney disease, there's 3 forms of modalities to sustain like, that's hemodialysis, peritoneal dialysis or kidney transplantation. 80% of patients who initiate -- who reach end-stage kidney disease, utilize hemodialysis as their primary form of kidney replacement modality. And why is that important? Because all of these patients will require a functional and durable vascular access. So here are -- this slide shows the 3 main types of vascular access for our hemodialysis patients. Each one has its advantages and disadvantages here. So on the left side -- on the left column here, we'll kind of go over briefly the advantages and disadvantages of the each access. So the arterial venous fistula, it is the preferred option for most patients, if a patient can have an AV fistula placed. The most -- the second most type -- most preferred type is an AV graft, which is a synthetic material connecting the artery and the vein. And the third type is a central venous catheter. So essentially a large IV catheter sticking in the heart. So in terms of the mid AV fistula, one of the main aspects, it takes several months, if not longer, for it to mature to be successfully use for dialysis. And AV graft, it -- you can use it in several weeks and in a catheter, you can use it immediately. However, in an AV fistula, while it's the most preferred access, the most common issue is oftentimes 50% of them never successfully mature to be used for dialysis treatment. In a graft, the most common issue is you developed frequent stenosis, which require interventions. And in the catheter, you have a high rate of infection, which causes great morbidity and mortality. So one of the main issues that we will talk about today is this disparity aspect, and we'll show some data showing that the large majority of patients who start with the fistula tend to be men more than women and minorities are less likely to use fistulas. In grafts, women and minorities are more likely to use an AV graft. And also, when we look at catheters, women and minorities spend a significantly longer time using a dialysis catheter. But not just the function of the vascular access, the quality of life is critically important. In fistulas, it is thought that it has lower complication rates, which may be beneficial for patients. However, you have to factor into the fact that a lot of fistulas do not successfully mature. So for grafts, you have to factor into the consideration that there are a lot of interventions to keep these grafts functional. So that also impacts quality of life. And in terms of catheters, there are a lot of complications related to infections and hospitalizations and this impacts morbidity and mortality. So where are the gaps in cares and the opportunities? I think, first of all, AVFs -- about 80% of patients who initiate dialysis, initiate with a catheter. So they're not using an AVF. We -- as I mentioned before, there's high maturation failure rates in fistulas and particularly in women, and I mentioned and will show that, have lower rates of fistula use. So I think the opportunity is that with the combination of processes of care and understanding biologies, we may be able to overcome these barriers and improve these outcomes. So what is the solution in an ideal vascular access? One is -- one opportunity is if you can place a vascular access like a graft, you can cumulate it early and patient will have less catheter contact time. A good access, you'll have minimal infection. That's, for example, an AV fistula, and you'll have better patency compared to a graft where it requires a lot of intervention. So I think there's an opportunity where we -- if we can develop novel conduits, which can address these 3 issues, I think this will really help patient outcomes as well as quality of life. So I think technology can change clinical paradigms. So next, I'm going to talk about the real-world data from the Frenova database, highlighting some of the background information that I just discussed. So this is a study population from the Frenova database that looked at 178,575 adults with a Charleston Comorbidity Index less than 8 and in-center dialysis patients. And they looked -- we included patients that looked at -- had a treatment for at least 1 year. So in this particular data set, they were looking at that access type within 90 -- patients within 90 and 100 days post hemodialysis initiation. And obviously, we're looking at the 3 different access types and also the combination of the access types and looking at the complications, and this is defined as per patient per year basis. So the definition of the complication rates was the sum of access-related events and the events that were looked at, including infections, removals, thrombosis, stenosis, cannulation issues, bacteremia, sepsis and placement of new access. So the follow-up period is a minimum duration of 1 year. So on the top here shows the different types of access and the combination of accesses here. And on the left side, we want to focus on the gender differences, male and female. I want to, first of all, highlight probably the most important aspect of this particular slide. So when you look at patients using AVF only, there is a dramatic disparity between males and females. So males significantly use fistulas more than females, 64% versus 36%. When you look at all the different combinations as well, too, so CVC plus primary AVG, AVG only, AVG plus primary CVC, females are more reliant on using a dialysis catheter and alternative conduits as compared to males. So again, this slide highlights the opportunity to address the gender influences for dialysis access. So the next set of analysis I'm going to talk about also comes from the Frenova database looking at complications. So this is from 2016 to 2019. So the purpose of this study, the goal is to address the influence of demographics and adverse outcomes in the population, again, was the Frenova database, you're looking at incident adults on hemodialysis with the Charleston Index score of less than 8, and this included approximately 87,000 U.S. incident patients. So the methods involved were -- the outcomes that we were looking at are 2-plus access infections within 6 months of hemodialysis initiation, 2-plus access failures within 6 months of hemodialysis initiation and the inability to come off a dialysis catheter at 16 months. So the analysis included the outcomes across all demographic groups and the events that we specifically analyzed were the hospitalizations, infection-related hospitalizations, 2-plus access changes in 6 months and 2-plus access infections in 6 months. So the duration of follow-up was a minimum of 1 year after initiation in dialysis. So this slide shows a forest plot here comparing men and women. So the outcomes, as I discussed earlier, here are on the left side, which are 2-plus access changes using only a catheter-only AVF not used, 2-plus serious infections and 2-plus access infections and multiple hospitalizations. So on this forest plot, I want you to look at the outcomes on the right side here, as I think they're really, really important here. So these outcomes here, greater than 1 highlight; compared to men, women are overall significantly more likely to have 2-plus access failures. You can see that here. This is greater than 1 remain on a catheter for at least 18 months after dialysis initiation shown right there and never use their AVF once it's placed here. So again, this is greater than 1 and then undergo multiple hospitalizations. So I think this particular slide in data highlight the fact that women have significantly higher risk of access failures for a long use of catheters, greater AVF abandonment and multiple hospitalizations. So when we look at an example of the potential costs in this subset of a group, so this is an access in obese diabetic women. So this is a women age less than 65, they are obese and diabetic women. As you can see here, the access complication rate is quite high, 1.59. So the estimated cost in this particular population is $258,000. If you compare it to other -- another contemporary type of population, much less. So the cost is $166,000 per patient year. So if you look at it -- if you compare these two populations, this group of women age 65 and less and diabetic, the cost of taking care of those approximately $91,000 more per patient year. So in conclusion from the slides and analysis that I've shown, we demonstrated that there are -- in 178,000 patients in in-center hemodialysis, patients not receiving a fistula were generally older, more likely to be female, and were less likely to survive to the end of follow-up. Secondly, women are more likely to fail AVF maturation and the cost is greater than $30,000 in the first year. So specifically women are 20% more likely to have AVF maturation failure. Women are 20% more likely to have multiple access failures in the first 6 months. And finally, women are 24% more likely to have multiple hospitalizations for access complications. So again, not only impacting the outcomes of the accesses, but also quality of life. So the final point I want to make is some female subgroups are especially at high risk, and I showed that in the previous slide. And this is an obese diabetic women population. And we showed that have excess costs up to $91,000 during the first year of hemodialysis treatments. So thank you very much, and I will turn it over to the next speaker, Dr. Mohamad Hussain, a vascular surgeon from Brigham and Women's Hospital.

Thank you so much, Dr. Lee, and thank you, everybody, for the invitation and the opportunity to discuss the findings of V007 clinical trial with you today. As Laura mentioned, I had the pleasure of presenting these data for the first time at the American Society of Nephrology Meeting last weekend and also I have the opportunity to use this conduit as an investigator in the V007 trial and V012 trial and look forward to the discussion today. So as you all heard, AV fistulas are generally the preferred method for initial vascular access in patients with hemodialysis. But failure of AV fistula maturation is a problem, and it can increase catheter use and catheters are associated with more infection, local and systemic as well as more issues with veins, like central venous stenosis where our central veins from the chest can really narrow up and cause further issues like arm swelling and of course, more mortality as well. ATEV or acellular tissue engineered vessel is a potential alternative vascular option for AV fistulas and their preliminary data that demonstrate low infection rates and without an associated maturation failure. So what is ATEV? I'm sure many of you are familiar with ATEV. But briefly, ATEV is a human engineered vessel that has grown from a bank of human cells. So briefly, aortic smooth muscle cells are seeded in a biodegradable scaffold and in then these cells are stimulated with biochemical and mechanical signals. The vessel is generated in a bioreactor bag, and after 2 months, the vessel is decellularized leaving behind a collagen tube, which is ready for human implantation by the surgeon. ATEV is available off the shelf and carries a half-life -- or shelf life for about 18 months. And after implantation, ATEV is infiltrated with more cells and its remodeled by the hose, much like native vascular issue. These unique properties make it more infection-resistant and potentially more durable than alternative vascular [indiscernible]. So V007 was the prospective multicenter, open-label, randomized controlled trial. 242 patients with end-stage kidney disease were on hemodialysis and were eligible to get an AV fistula or AV graft were randomized across 30 centers in the United States. They were randomized in a 1:1 ratio either to ATEV or AV fistula, which were implanted in the upper extremity by the surgeon. All patients with the study access will be followed for 2 years. Here's the key inclusion criteria. So adults with ESKD who were receiving hemodialysis and were eligible for AV fistula or AV graft creation. The key exclusion criteria was candidates who were able to get the optimal AV fistula were excluded. That's generally a 1 stage first time radiocephalic in the distal forearm with an excellent radial artery and cephalic vein. Here are the outcomes. The primary efficacy outcome was a co-primary endpoint of functional patency at 6 months and secondary patency at 12 months. Functional patency, which was adjudicated, was defined as 2-needle cannulation for at least 75% of the dialysis sessions over a 1-month period. And secondary patency is freedom from abandonment of the access. Duration of the access use over the first year was a key secondary outcome. And there were a host of safety outcomes; importantly, infections related to the access over the first year as well as other adverse events and interventions related to the access in the first year. So here's a look at the baseline characteristics of the patients in the clinical trial. 123 patients received ATEV and 119 received AV fistula. The mean age was between 57 to 60 years old. About 1/3 of the patients who were above the age of 65 years. Around 30% of the patients were female. 35% to 40% of the patients were obese, which is defined as a body mass index greater than 30. 2/3 of the population was diabetic. And the mean or average catheter use prior to enrolling and randomization was just over 4 months in both groups. And here is the top line results of the trial. Functional patency at 6 months was 81% in the ATEV group and 66% in the AV fistula group. Secondary patency at 12 months was 68% in the ATEV group and 62% in the AV fistula group. The p-value was highly statistically significant in favor of ATEV 0.0071. Now what was really interesting is looking at the subgroup analyses. So you can see on the left side, 3 main subgroup analyses were conducted: Patients who are diabetic versus nondiabetic, patients who are obese versus not obese and patients who are males or females. And when you look at the relative patency and the p-values, you'll notice that all 3 subgroups, which are defined as high risk subgroups, diabetic patients, obese patients and female patients were the ones who particularly benefited from ATEV over AV fistula. And you can see that with the lines, the horizontal lines in the middle of the forest plot are all in favor of ATEV to the right of the relative patency as 1.0. In fact, the strongest signal with the highest relative patency was in the female subgroup in favor of ATEV. Here's a look at duration of access use for the first year. Once again, we'll start with the very left bar graph. In the overall group, ATEV was used for a longer period of time over the first year, 7.5 months in the ATEV group of access use compared with 6 months in the AV fistula group. And once again, it was the high risk subgroups that benefited most with ATEV. Looking at females, they use the ATEV for over 8 months compared with fistula for 5 months. Obese patients used ATEV for nearly 8 months compared to 4.5 months for AV fistula. And diabetic patients used ATEV for 7.5 months compared with 5.5 months for those who received the AV fistula. Now let's look at some safety outcomes. First and importantly, infection rates. So the first line will show hemodialysis access-related infections. So that's all infections, whether it's a catheter-related infection or an access-related infection. And the rates are very similar, 9.1% in the ATEV group and 9.9% in the AV fistula group. And when you break that down by blood stream-related infections or local infections, the rates were also very similar, roughly 5% bloodstream infections and 4% local infections in both groups. And when you further break that down and narrow it down to only surgical access-related infections, the rates were very low in both groups, 3.3% in the ATEV group and 0.8% in the AV fistula group. Here's the look at other adverse events that were noted in the trial. So in the ATEV group, overall, there were higher rates of thrombosis, stenosis and pseudoaneurysm formation compared with AV fistula. The rates of true aneurysms were very low in both groups at 1.7%. There were no ruptures of ATEV during follow up and there were 1.7% rate of AV fistula rupture. And the rate of steal syndrome was also higher in the AV fistula group, 5.8% versus 0.8% in it. So what happened to the thrombosis in the ATEV group? Well, of all the patients who has thrombosis, out of 63, 59 patients or 94% of the patients successfully were treated for thrombosis event with an intervention and they were able to be taking secondary patency. Here's a more detailed look at the types of interventions that occurred in both groups. Not surprisingly, more angioplasty, stenting and thrombectomy, endovascular interventions were carried out in the ATEV group. On the other hand, AV fistula group required more balloon-assisted maturation to help the access mature, whereas none required balloon-assisted maturation in the ATEV group. Also, more patients in the AV fistula group required surgical revision, 23%, compared with surgical revision 10% in the ATEV group. So in conclusion, in this clinical trial, ATEV was superior to AV fistula in patients with end-stage kidney disease on hemodialysis with respect to a 6-month functional patency, 1-year secondary patency and 1-year access usability. Outcomes with ATEV were most improved in the highest risk subgroups. These were female patients, obese patients and diabetic patients. ATEV had a comparable safety profile to AV fistulas with overall similar rates of infections in both groups. There was a lowering need for maturation procedures and surgical revision procedures in the ATEV group. However, patients who receive ATEV required more thrombosis treatment and maintenance interventions, although the majority of these cases were successfully treated. For the future, we look forward to the V012 clinical trial, which is a Phase III multicenter prospective randomized control trial of ATEV versus AV fistula in female patients with end-stage kidney disease on hemodialysis. The trial is currently enrolling with a target of 150 patients. And the primary efficacy outcome will be to compare freedom from dialysis catheter or study access abandonment and safety outcome will be the number of infections in the first year. Thank you, and I'll turn it over to my partner, Dr. Keith Ozaki, John A. Mannick Professor of Surgery at Brigham and Women's Hospital and is very familiar with the conduit and has been involved with these clinical trials in dialysis access point in time.

Thank you, Dr. Hussain, I appreciate the opportunity to talk about this conduit. I'm going to go over a case that actually I was taking care of when the team at Humacyte asked me to discuss this conduit in a particular patient. This is a 57-year-old lady with end-stage kidney disease who was getting hemodialysis by a catheter. And I was asked to see her for permanent dialysis access placement. She's a typical patient, diabetic with hypertension. She also has medical conditions like lupus. And she actually had a cerebrovascular accident, was on an anticoagulant for that event. Her body mass index was 30, and she had contractures in her right arm and leg, so we kind of had to focus on the left side of her body. She had no arterial disease, palpable radial artery pulses and I couldn't really see veins on exam. So we went to what's called a venogram where we inject dye in a vein to see what we have for options for access creation. As you can see from her silhouette, her arms are quite large, and you don't see very good veins. On the right-hand image those are all too small to use for primary access. And really, at many places around the country, I think the axillary vein, the one in the far left lower corner, is really the only vein that could easily be a target for a high flow access. And many places would do a brach-ax or brachial artery to axillary vein access or an access that is axillary to axillary as her first access. We've taken a slightly different approach and that we like to grow up the inflow and the outflow of an access and try to stay out of that axillary vein because once that starts scaring down and you get a couple of devices in there like a stent graft, you lose that extremity. And here, this lady really doesn't have good options on the right. Dr. Hussain and his team have published this in a paper last year. And basically, what we did is we took the proximal radial artery, that's a lower flow artery and hooked it to a small vein and then we waited a couple of months. And then we let the artery and vein grow up. You see the image there in the middle, the vein and the artery have actually matured to a certain extent. And then we come back with a second operation, and we create a cannulation zone. We do what's called an interposition graft. And typically, we do PTFE or an autograft that's a bovine carotid is that interposition cannulation zone. It does introduce a prosthetic material that in our hands is about 1 out of 10 will get infected, but it really does offer a way to get the catheter out about a month after the second stage. Unfortunately, this is a picture depiction of the inflow and the outflow that has matured. This is not this patient, but this is a typical patient, and here, you see us sowing that interposition graft into this much larger artery and vein, and it makes for a nice controlled flow access that does use in about a month. Unfortunately, for this patient, she missed an early post-op appointment, and she actually came in about a month post-op with a wound infection at her anastomosis. And this is a situation that really is unsalvageable for this prosthetic material. And thus, she's admitted to the hospital. She has to undergo a total graft excision. We gave her a little line holiday. We rest her without a prosthetic material body because she's circulating bacteria throughout her blood and we give her IV antibiotics. She was in the hospital for 11 days. She's getting complicated wound dressings, et cetera. Our overall plan is next month, we'll take her back to the operating room and hopefully use some of that slightly larger artery and vein in the upper arm now that we can somehow create an access likely it's going to require 2 stages, likely it's going to require some sort of prosthetic material. And again, this is not an unusual case. This is kind of the typical case we would see in our practice. I bring her to this forum because I think this is the kind of situation where an ATEV could have several applications. Number one, she is a high-risk patient as we know, she's female, diabetic, slightly obese, et cetera. And I think these types of selected patients, it may make sense to get her catheter out to go with an initial brachial to axillary conduit, get her catheter out at a month, and they can use that while she's undergoing her bridge to transplant. We also could have used out our revision and stayed in the form. Rather than using PTFE or an autograft, we could have used this conduit as the interposition conduit. And I think it would have had a very, very, very low risk of infection. One of the refreshing things about this conduit from a surgeon's perspective, is that really the infection rates are like an autogenous construction rather than that high infection rate we see with prosthetic materials in this high-risk patient population. Furthermore, and this is why I'd really like to get this on our shelf as frequently as surgeons were faced with the field that's contaminated or even grossly infected. And I could have immediately reconstructed her at the time of removal of this prosthetic graft and use that same inflow and outflow, gotten that catheter out much quicker at time, she's very high risk of getting a cater infection in endocarditis and other horrible things associated with systemic bacteremia. So even if I didn't do it at that very initial operation, even that same hospitalization, I could have done this in short order. And then finally, we may identify certain patients who have struggled with PTFE, bovine carotid, conduit, et cetera, and those select high-risk patients that are at increased risk of infection. And those might be patients that have diabetic foot wounds, et cetera. Those are the ones that we would preemptively put in this infection-resistant material to avoid the kind of long hospital stay, the morbidity that these patients suffer. So Tara, I'll turn it back over to you now at this point, and thank you very much.

[Operator Instructions] So our first question comes from Kristen Kluska at Cantor Fitzgerald.

Congrats on the data that you recently presented at Kidney Week. So I have two questions. The first one is just given the different disparities in use across the 3 forms of standard of care, where do you best see the ATEV fitting in? Will it initially be used in those 3 higher risk populations where the data appeared more strong? And then the second question I had is I was hoping you can give us more color around the thrombosis, namely how serious this is, given the percentage observed here? Do you anticipate anything in the protocol in place to keep an eye out for it during follow-up? And any color about when the thrombosis occurred as well?

Well, I'd be happy to attack that as someone who's seen a lot of access practices around the country. And one of the things that strikes me and Dr. Hussain has published a lot on this, and I encourage you to look at his papers in a recent presentation at New England vascular last weekend. But there's huge heterogeneity in access care around the country. And that some practices have high use of prosthetic materials. Many accesses are placed by surgeons and practitioners that do very few accesses. And so I think each little practice will be different. I don't think this is something you can say, "Well, come out and everybody across the country will use this at 60% of cases." So I think I can best talk about what we do in our practice. And will this be a panacea for everything. No. But at the same time, this is one of the biggest jumps in technology that I've had over my career in this space. And so I do see us selecting -- using it in high-risk patients that have been defined. I can't wait to use it in situations where I am concerned about infection. And then, of course, there are many off-label things I'd love to use it for portal vein reconstructions in cancer cases. I'm doing an oncologic case with OB/GYN team today, and those are clean contaminated cases and as a conduit and patch material, et cetera, I think it would have a great utility for the vascular reconstruction that I do. And then the second thing about the thrombosis and just a couple of quick on comments on this. I've seen this kind of come into clinical practice, and it really is completely different. And I think one of the lessons is, we'll have to learn how to -- what kind of instruments to use, how to handle it. I do worry that it's very soft and our cannulation centers are used to a stiff PTFE graft or something they'll put a compressor dressing on it. And we have to recognize that this is basically exposed sub-endothelium. It's prothrombotic early until it does heal in and there may be opportunities for bridging with antithrombotic agents in the early period until this conduit has healed and gets an endothelial line, et cetera. And I know that, that early phase is something that could be well tolerated with a little anticoagulant or antiplatelet in the early period. I'll point out, and this is something that we haven't talked about with the Humacyte team, but you really did exclude people that have that perfect fistula at the rest, the Cimino, the snuffbox fistula. But in our hands, those lower flow accesses are actually ones that get a lot of early interventions. I challenge you to look at our snuffbox paper in the Journal of Vascular Surgery. And so that early thrombosis rate, if we do a low flow access, a lot of those do get thrombectomies. If they get treated with -- by a simple outpatient procedure, et cetera, you don't lose your access, that's a key thing, but it's kind of not unexpected, I think, in the early experience of this. And the important thing that we really care about, will this have a durable secondary patency, will it keep the catheter out. I'll let the others comment now, sorry.

Yes. I mean, I'll just say this along the bigger picture here. I think this is a great opportunity these days. There's -- a new set of KDOQI guidelines, the kidney disease outcome quality initiative guidelines, that were published in 2020. And one of the main things that came out of it is the right access for the right patient for the right reasons. So we are not now boxed into just placing AVFs in patients. So we have the opportunity, I think, to really utilize new technologies. And along those same lines, CMS on this past year, got rid of judging dialysis centers for the number of fistulas that you're placing, right? So we're no longer judged on that. We are still judged on catheter use. So I mean, I think this is a great opportunity for new technologies to get patients off of catheters. So I mean, I think there is a more patient-centered focus now to put place the right access in them and to get them off from catheters. So I think newer technologies, this is a great time for them.

I'll add that. Some of the data that Dr. Ozaki was referring to that we had looked at national practices across the U.S. in terms of dialysis access patients. Patients who received an AV graft were a lot more likely to be women, about 60%, whereas people in the fistula group are more likely to be men. So I do think that women having smaller vessels, smaller artery, small veins to begin with, and then you had another risk factor such as obesity. And we can clearly see that in the real world, those patients are already getting a prosthetic graft where the infection rates are significantly higher than 10% or so per year. So I do concur that these are some of the high-risk group that had, as a surgeon I will be looking to see that this is a better option for them than creating the high-risk fistula or using a prosthetic graft.

Our next question comes from Josh Jennings at Cowen.

I wanted to just follow up on the last two answers about the patient group that is not a candidate for AVF. And just remind us how big that is and how you see the ATEV penetrating that non-ATEV candidate patient group that's in need of AV access?

Probably Dr. Hussain can best comment on overall nationally, how many people start off with a fistula as their first permanent access versus a prosthetic.

Yes. Happy to comment on that. So again, according to data that we looked at around 50,000 patients who received a first-time access over the last 10 years in the U.S. AV fistulas were most common, around 80% and an AV graft were about 20%. But it's important to note that this is just what the patients received as their first-time access. Of those 80% AV fistulas and we don't have great data outcomes, many of the AV fistulas will fail because they're the high-risk patients. So what we envision is that some of those -- anticipated some of those high-risk fistulas, one would think about using alternative conduit if it's available.

And I'll add too, in that our highest use of prosthetic materials is for our revision procedures. People with a fistula will wear out their cannulation zones have stenosis, et cetera, that become recurrent to balloon angioplasty, and we leverage that current inflow and outflow and revise that access. And I know industry very much focuses on new permanent accesses but a new technology we're evaluating with another company actually is including people that get a revision. And those revisions are times when I'd love to use an HA -- excuse me, an ATEV because it's an alternate situation where there's been recent punctures of that fistula and there's often little micro absences, et cetera, and it's a little higher risk of infection. So you can't just look at new access creations but also include the revision world, and we do 2 revisions for every new access creation we do.

That's super helpful. And then I just wanted to ask about the control group, the AV fistula arm and just the performance functional patency is 66.4%, secondary patency 62.2%. Is that an outperformance relative to, I guess, the clinical community's expectation and what you see in the real-world experience?

I would comment, and again, these are some of the data that we have published that this is very in line with what we would expect with AV fistulas. Now it's important to note that in the control group, they were both upper arm fistulas and forearm fistulas. In fact, they were more upper arm fistulas. About 3/4 of fistulas in this trial -- in the control group were upper arm fistulas and they tend to have higher patency than forearm fistulas. So I think that the group -- anything the control group is performing a little bit better because you have brachial artery based upper arm fistulas. But overall, my sense is this is very in line with what we see in patients and other sort of clinical trial data for outcomes of fistulas.

There were also a lot of men in V007 and men mature their fistulas more frequently.