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 available on the Humacyte website following the conclusion of the event. I'd now like to turn the call over to your host, Dr. Laura Niklason, Founder, President and Chief Executive Officer of Humacyte. Please go ahead, Laura.

Good morning, everyone, and thank you, Tara. I'm very excited to be doing this presentation this morning, which is an event with several of Humacyte's key opinion leaders and titled Hemodialysis Care, A Crossroads of Care. And this specifically targets confronting the complications and costs that are associated with hemodialysis access, using Humacyte's Human Acellular Vessel innovation. On this call with me today, there is myself. There's also Dr. Shamik Parikh, our Chief Medical Officer; and those are the 2 folks from Humacyte who are going to be speaking on this call today. In addition, we have several key opinion leaders from the nephrology and surgical spaces who are going to be joining us and providing their insights into some of the complications and some of the disparities and inequities that we see in hemodialysis care. If we could just go to the next slide, I'm going to ask people to introduce themselves in a minute. But I will kick off just with the acknowledgment that all of this research that we've done into the complications in hemodialysis care have been done with our close partner, Fresenius Medical Care, and their research arm Frenova. During the past year, Humacyte has partnered with Frenova and their data analysts to really dig into some of the complications and observations that occur in the tens of thousands of hemodialysis patients that Frenova treats and tracks every year in the United States. And with that, before we get to the presentation outline, I would like to ask some of our key opinion leader guests to introduce themselves. First, I'd like to ask Dr. Timmy Lee from University of Alabama, Birmingham, to introduce himself.

Thank you so much, Laura. Thank you for the invitation to be on this webinar today. My name is Timmy Lee. I'm a nephrologist at the University of Alabama at Birmingham and Professor of Medicine. I've been interested in this particular area since I was an intern over -- at Internal Medicine over 20 years ago. At that time, I saw patients being admitted to the hospital with catheter infections and because their dialysis access was not working, particularly fistula is not maturing. So that led me really want to study this particular problem of how to improve dialysis vascular access for patients. And over 20 years later, we still do not have adequate solutions, both for creation as well as maintenance. So that's what drives me to help develop new therapies for our dialysis patients.

Thank you, Timmy. Next I would like Prabir Roy-Chaudhury from the University of North Carolina at Chapel Hill to introduce himself.

Wonderful. Thanks so much, Laura. My name is Prabir Roy-Chaudhury, I'm a Professor of Medicine at the University of North Carolina at Chapel Hill, so close to Humacyte actually geographically. I'm also the Co-Director of the UNC Kidney Center, and for -- again for probably 25-plus years now, have had a dedicated interest in vascular access. I very clearly think that a close partnership between clinicians and industry is absolutely essential to get new vascular access products into our patients who are really waiting desperately, I would say, for the -- and as Timmy said, for over the last 2 decades. And so I personally am very excited about what we're going to be talking about, and I really look forward to the back and forth with all of you. Back to you, Laura.

Thank you, Prabir. And then lastly, I'd like Dr. Michael Curi from Rutgers University to introduce himself.

Hello, everybody. I'm Dr. Michael Curi. I am Associate Professor and Chief of Vascular Surgery at Rutgers New Jersey Medical School. As a vascular surgeon, we are typically the ones who are creating dialysis access for patients requiring hemodialysis. And here at Rutgers, we both take care of patients on a day-to-day basis with these conditions, but also are actively engaged in discovering new ways to take care of these patients and all patients with vascular diseases. And we've been integrally involved with the clinical trials studying the use of the HAV and I look forward to sharing our experience with you guys.

Thank you, Mike. So just very briefly, at a high level, before I turn it over to some of the other speakers in the program. Our presentation is going to go as follows. First, we're going to broadly review the types of access that are available for patients currently with current technology. We're then going to go into a deeper dive into some of the data that Humacyte and Frenova have been able to pull out together during our partnership over the last year. We'll then touch on some of the economic considerations and the implications of both the access outcomes and the economics, particularly for women who are on hemodialysis. We'll then turn our discussion to the HAV and some of the inherent properties and the product profile that has emerged on the HAV during our years of clinical experience. And then we'll ask Dr. Parikh, our Chief Medical Officer, to walk this group through the our just started hemodialysis study in women to really -- that's designed to really pull out some of the advantages that the HAV may provide female patients. Next slide, please. So with this, I'm going to stop talking now. I'm going to turn it over to some of our experts. Dr. Lee, I think, is going to be taking the next slide.

Thank you. So I think before we can talk about the different types of dialysis accesses, because I think there are a number of a broad audience here. I think we need to set the landscape. So first of all, in the United States, there is a growing population of patients that are reaching what we call end-stage kidney disease. So when you reach end-stage kidney disease, in order for the patient to sustain life, there are 3 forms of kidney replacement therapy that's possible, that's either hemodialysis, peritoneal dialysis or kidney transplantation. So the large majority of patients in the United States, almost 70%, 80% utilized hemodialysis as their primary form of kidney replacement therapy. So in order for hemodialysis to work, you need access to the bloodstream. And there are 3 main types of access a patient can utilize to successfully perform hemodialysis, and I'm going to start from the right here from central venous catheters and then talk about grafts and fistulas. And then -- and talk a little bit about the preferential use, maturation time, complications, disparities and quality of life. So the first 1 I'm going to speak about on the very right is a dialysis catheter. So dialysis catheter, the advantages is that you can place it and use it the same day. This is actually the most common form of dialysis access that a new dialysis patient starts off with. So 80% of hemodialysis patients that initiate dialysis use a central catheter. So again, the advantage is that you can use it immediately that same day, but the major disadvantage is that you're having a IV sticking in your heart. So you have a great number of infections and also getting adequate dialysis clearance is challenging many times with the catheter. In recent years, we've learned over the last 10 to 15-years that women and a large number of minorities such as African Americans utilize dialysis catheters in compared to other populations. And the impact of quality of life as I mentioned, and this is when I first started as an intern, a lot of hospitalizations due to infections and increases mortality as well too. So also restrictions on daily activities, very simple ones, such as taking showers. So the next access that I'll talk about is arteriovenous graft. So oftentimes, most often, this is like a synthetic graft, PTFE, connecting the artery and vein. It is better than using a central venous catheter, and so the advantages are, once it's placed, it can be used typically -- cannulated typically in 3 to 4 weeks. But there are grafts that can be cannulated at the same day. It has -- compared to a fistula, it has a higher risk of infection and stenosis and thrombosis, but it is a better access than compared to a catheter. I am also in large observational studies, women typic -- are more frequently using grafts compared to men and also a larger number of African Americans. So there are disparities in use of AV grafts. And the main impact in terms of quality of life is that grafts commonly develop stenosis requiring a number of interventions to maintain and sustain patency. So they have to go to the interventional radiologists or nephrologists quite often. And the most preferred access here on the left that I'll talk about is the arteriovenous fistula. So essentially just connecting the age to the vein. The high pressure from the artery helps the vein dilate and you cannulate the vein. So for a number of years now, it's been considered the first and most preferred option for hemodialysis patients. But the challenging thing is, particularly in the United States, is once a fistula is placed, it takes from 6-weeks to oftentimes longer than 6-months before it can be successfully cannulated. And the major issue related to arteriovenous fistulas is up to 60% are never successfully used for dialysis. Complication wise, if it's successfully used, and I'll use the term successfully used, it has lower risk of infection and stenosis and thrombosis compared to grafts and catheters, but in terms of the large observational studies, majority of men, there's more men that have successful -- that are successfully using fistulas compared to women, and also in terms of minorities, they seem to use less fistulas compared to the white population. But if you can get a fistula to successfully mature, the quality of life is much better due to lower rates of complication and infection. So back to you, Laura.

Thank you very much. If we could go to the next slide. So Shamik, if we could ask you to cover this, please?

Thank you, Laura. So the HAV has the ability to address some of the access problems that Dr. Lee walked us through. In particular, if you look on the left of the slide, the HAV comes in standard diameter of 6 millimeter, which is ideally suited for AV access, and therefore, it does not require the size maturation that we often have to wait in cases of AV fistulas. Our HAV can be cannulated within 1 month. So again, it reduces the waiting time of several months with AVF. And HAV is able to reduce catheter time and has decreased risk of CVC infections, again, because of the ability to use it sooner. As you are aware, or most of the audience on this call, the HAV is made up of human extracellular matrix, and this invites the host cells once implanted to populate it. And this repopulation by the cells allows the HAV to fend off infections. It makes it resistant to infection, and this has been proven both in AV access and in other indications where HAV has been used, it has a very low rate of infections. In addition, this also allows the HAV to heal itself upon cannulation. So all in all, we are looking at reductions in catheter contact time. We are looking at the infection resistance properties of HAV and the lower failure rate. And this has the potential to benefit the patient who are challenged with AV access and also help reduce cost. If you go to the next slide. So Humacyte is currently conducting a head-to-head study between HAV and the gold standard AV fistula. This is study 007. This is a Phase III trial, and we are looking to compare both the efficacy and safety of our HAV with that of an autogenous arteriorvenous fistula in patients with end-stage renal disease. So in this trial, all subjects who -- with end-stage renal disease who are suitable for a single-stage AVF have been enrolled for -- the target was 240 patients, and we have completed enrollment of this study last year, 242 patients enrolled in the trial and this will provide us with meaningful information for comparison of HAV versus AVF. The trial was enrolled in April 2023, and we will be approaching the 1-year time point within a few weeks this year. The endpoints of this trial are looking at usability for dialysis and patency during our first year. We are also looking at a number of safety endpoints, including infections, interventions, the duration of patency during this study. Overall, the subjects are followed for 24 months. However, we will be evaluating this study at 1-year time point, which is, as I said, in summer of this year, and the top line readout is expected to be towards the end of summer in 2024. This trial also allows us to look at some of the subpopulations that we will be enrolling in the study such as males, females as well as elderly patients. And to tell us a little bit more about some of the challenges faced by some of these populations. I'm going to hand it over to Dr. Prabir Roy-Chaudhury.

Great. Wonderful. Thanks, Shamik. If we could have the next slide. So what I'm really going to do over the next 2 slides is to put a human face, a patient's perspective onto the information that we've heard. And as a clinician, I think this is absolutely critical. This is why we're doing the things we do. And this is a real patient. This was 20-years ago. I was much younger and had more hair. She was a 28-year-old black female. I clearly remember her. She was tall and quite slim, and she had end-stage kidney disease due to focal segmental glomerulosclerosis, which is basically inflammation in the kidneys. And I saw her together with her husband in the pre-transplant clinic and I was extremely positive about our prospects for a transplant. I was hoping that she'd be able to get a living donor transplant. I remember telling her "the transplant is going to change your life. You're going to be able to have kids. You're going to be able to work. You'll be able to lead a normal life". There were 2 problems, though. And at that time, I didn't realize the impact of them when I first saw her. The first is that she was a -- she had a tunnelled dialysis catheter already in place. And the second that we'll speak about the importance of that, that she was obviously a woman. I saw her next 3 months later in a vascular access clinic that I used to do in Cincinnati with a surgeon. And everything had changed. So this woman that I was so positive about earlier in terms of her being able to get a transplant, she was paraplegic and in a wheelchair. So basically, her lower extremities were no longer working. And when I put together what happened, what happened was that she had gotten arteriovenous fistula placed, but it didn't mature. And because the fistula didn't mature, as Timmy has said, there's a very high frequency or incidence of failure of these fistulae. Because it didn't work, she had a prolonged duration of time, during which she had, had tunneled dialysis catheter, which then got infected. There were bacteria in her blood stream. The bacteria latched on to her heart valves. That's a condition called infective endocarditis. And then the septic emboli, if you will, flipped off those heart valves, went to the spine and resulted in a [ abscess ] around her spine that compressed her spinal cord. I want us to look at this case, not just to identify the gaps in care, but to try and use the case to identify solutions. And I think that, that's critically important, because these problems have remained exactly the same over the last 25 years. And I really believe that we can do better. I'm going to change that. We absolutely, as a kidney community and as a surgical community, need to do better by these patients. So if we could have the next slide, please. So what are the gaps in care? And again, Timmy did this beautiful overview, and I'm just going to emphasize some aspects of that. So the first gap in care, of course, is that as a community, we did not create a fistula prior to her starting on to dialysis. And the reality is that this is a huge process of care issue. 83% of patients starting hemodialysis in 2022, started with a tunneled dialysis catheter. So that's clearly 1 gap in care. But the other very big gap in care is that the fistula that was placed did not mature. And so she had this catheter for a prolonged period of time. And it was really this combination of process of care together with biological barriers that resulted in the terrible outcome that I described to you truly from hope to tragedy. So what are the solutions? So I'm going to submit to you that if in the future or if 20 years ago, we had a vascular access device that allowed 1 to do early cannulation, sort of like an arteriovenous graft to reduce the duration of tunneled dialysis catheters. But at the same time, just imagine that this vascular device had a minimal infection rate, sort of like an arteriovenous fistula. And then as the icing on the cake, just imagine that this actually had better patency, at least as compared to the arteriovenous graft and may be equivalent to or even better than the arteriovenous fistula. Wouldn't that have changed that young woman's course? And I'm going to submit to you that the Human Acellular Vessel actually, if it works as we expect it to, could actually fulfill all of these criteria. I just want to share -- end really by emphasizing something that I have believed in very, very strongly throughout my career. And that is that technology can, in fact, completely change clinical paradigms. So again, just imagine that we had a device such as the HAV or another similar device, that would allow us to go from this, one-size-fits-all sort of fistula-first approach that we've pretty much followed till now, to a clinical paradigm that is HAV first, tunneled dialysis catheter last, particularly in a specified group of patients. And I hope that we'll be able to see that -- I hope I'll be able to see that during my career. So with that, Laura, I'm going to hand back to you.

Thanks so much, Prabir. If we could go to the next slide. So what I'm going to do here is I'm going to summarize some of the work that Humacyte and Frenova have done in partnership over the last year. So just to provide an overview of the database that we examined together, this is an evaluation of data from prevalent dialysis patients that were cared for within the Fresenius system between 2016 and 2021. This is a huge data set, over 170,000 patients, all treated with hemodialysis. And in addition, I'd like to point out that of these 178,000 patients, all of them were actually relatively healthy. So this analysis by choice excluded patients who are gravely ill while on dialysis, and that exclusion of gravely ill patients with a very short life expectancy was really meant to focus on patients who were going to be on dialysis more chronically for many months and perhaps years and perhaps a decade or more. So we focused on patients with the Charlson Comorbidity Index or CCI of less than 8. We also focused on patients only who were treated on dialysis for at least a year. And we did multiple types of analysis, some of which I'll walk through with you this morning. We looked at what types of access patients were using within 3 or 4 months of initiating dialysis. In other words, what fraction of patients had successfully come off their catheter, because we know, as Timmy and Prabir noted, more than 80% of patients start on a catheter. So at 3 or 4 months, what fraction of those patients have managed to come off, what types of access they're using, what types of complications and the frequency of complications that they're having. The follow-up time on these patients, because this was a long time period in a large database, was also substantial. The average follow-up was over 3 years. So this is a very robust analysis. Next slide. So just -- I'm going to show a lot of numbers here in the next slide, and I apologize for that. There's a lot of information here that we've tried to distill and these are some of the key points that we think jump out from the analysis. So if you look at this table here, on the top of this table is different types of access that were used by the patients overall. At the 3- or 4-month time point after initiating hemodialysis. So on the left, in this table, we have catheter-only, and we have combinations of catheter plus other types of access that may or may not be working. We then have fistula in purple, and then various types of grafts plus/minus indwelling catheter. And again, the total number of patients that were receiving these different types of access is shown in the top row in this table. But then I'd like to point your eye to the 2 bottom rows in this table, where we break down the patient percentages by male and female. If we look at the fistula column, what Timmy and Prabir pointed out earlier in this webinar is clearly true. So if we look at 3- or 4-months after initiating dialysis, only 36% of women are using a fistula, but nearly twice as many men are using a fistula at that time point. So that's an enormous disparity that actually -- although I was expecting to see this was bigger than I was expecting. And I think bigger than many folks who understand the space were expecting. Women use fewer fistulas. And, of course, going along with that, women use grafts and catheters more frequently. So if you look at the light yellow columns here, what you'll see is that the percentage of women who use a catheter primarily plus a graft is about 58%, whereas with men, it's only 42%. And if we look at patients who are using grafts only or graft with a supplemental catheter, again, it's more than half of women are using those inferior modes of access. Next slide. If we look at odds ratios, which is really a comparison of the rate of risk of using a particular type of access for men versus women or for black patients versus white patients, again, we see really stark differences. So if I can point your eye to the first row in this table, this is a list of the odds ratios or the relative risks that a woman will have a particular type of access as compared to a man. And as you can see, the top row shows clearly that women are nearly twice as likely than men to be burdened with a catheter primarily that supplemented with a graft or a graft only. And conversely, not surprisingly, women are only -- 70% is likely to have a functioning fistula at this 3- or 4-month time point. If we look at the impact on black patients as compared to white patients, these numbers are almost as stark, where black patients are 50%, 60%, 70% more likely to have an inferior access of specific types as compared to white patients. So both women are clearly burdened with inferior access and also African-American patients. Next slide. When we talk about inferior access, some of the points that were brought out by Timmy and Prabir, such as complications, loss of patency and importantly, infections are obviously things that we think about. However, if we quantify the total complication rate, and this is complications per year, to include loss of patency and intervention to restore patency, intervention to create a new access, treatment of access infection, hospitalization for access infection. We add all of those complications together and look at the aggregate complication rate. What we can see is that overall complication rate is strongly driven by access type. So if you have a functioning fistula, then your complication rate over several years is about 1.7 -- a median complication rate of about 1.7 complications per year. However, if you're burdened with a catheter or with a graft or some combination of those 2, complication rate is nearly twice that. So these are nontrivial differences. These are significant and nontrivial differences in complications, adverse outcomes and cost of care for patients who are burdened with grafts and catheters as opposed to fistula. Next slide. So looking -- after that high-level view of types of access and overall complication rates, we then decided to do another type of analysis and to look specifically at the impact of demographics on types of complications that are suffered by dialysis patients. And again, these complications are only implications relative to the access. So of course, dialysis patients are burdened with multiple diseases. And the types of complications that we focused on did not have to do with their underlying kidney disease or other associated ailments. All of the complications that we focused on had to do strictly with problems with their dialysis access. Again, we focused on the same patient population of more than 170,000 patients. And again, we -- I'm sorry, I spoke an error. This population was a little bit narrower. We focused on about 90,000 patients. But again, we limited this to fairly healthy patients with a Charleston Comorbidity Index of 8 or better. We looked at several types of specific outcomes. We looked at hospitalizations that occurred because of problems with access. We also looked at the rate at which patients developed 2 or more access infections just in the first 6 months of care. And we looked at the rate of patients who developed 2 or more access failures in the first 6 months of care. So all of these types of complications, being hospitalized due to access, having at least access infections in a 6-month period, having 2 access failures requiring new placement of access within 6 months. These are all highly impactful and expensive complications for the system that also carry a lot of morbidity for the patient. And again, we limited our analysis to patients who were followed for a duration of at least 1 year. Next slide. As you can see, looking at hospitalization rates, -- this is a very broad view. But as you can see here that at all time points, women are between 10x and 14x more -- 10% and 14% more likely than men to be hospitalized from their -- from a access complication. And this is all women. This is not just women who are burdened with a graft or a fistula or a catheter. So this is all women on dialysis overall are more likely to be hospitalized for access problems. Could we go to the next slide. So there's a lot of data on this slide. I think it's worth taking a little bit of time to absorb it. This slide shows the odds ratios or the relative risk of women as opposed to men suffering some of these complications that I mentioned 2 slides back. So specifically, if we look at the odds ratios that a woman in the first 6 months will have 2 or more access failures, we can see from the odds ratio shown here that, that overall that odds ratio is 1.2, meaning that women are 20% more likely to have 2 failures in the first 6 months. And that difference for men is significant, that the P-value for actually -- for all of these associations is very small. So all of these observations are significant. The chances that women will have to rely only on a catheter for at least 18 months after dialysis initiation as compared to men, that's also a significantly elevated risk. And in addition, women are 24% more likely to have multiple hospitalizations for their access as compared to men. So this is just another way of quantifying the overall risk of specific complications that women suffer overall as compared to men. Next slide. So in conclusion, and I'd like to say that the data that we've shared here from this analysis is actually a small subset of the data that we've cleaned. We've tried to provide a very high-level assessment to show that on an objective basis, looking at many thousands of patients, women are fundamentally disadvantaged in terms of the types of access they're able to attain and also the numbers of complications and the types of complications that they suffer relative to men. So overall, looking at nearly 180,000 women in the U.S. undergoing hemodialysis, patients -- women patients and are more likely to be dialyzed on a graft plus or minus a catheter, and that patients who are dialyzed on a graft are more likely to be older, more likely to be female, and more likely to be black as compared to white patients. In contrast, patients with a functioning fistula are more likely to be young and more likely to be male and more likely to be white. And were more likely, in large part, probably because they were able to have a fistula and to avoid infectious complications, those patients were also more likely to survive throughout follow-up. Access type is strongly correlated with complications of hemodialysis access. And not surprising to the KOLs on this call, grafts and catheters have significantly higher rates of overall complications. In fact, it's almost a 2x impact. Women and black patients are more likely to use grafts, plus or minus catheter and because of that have substantially higher complication rates, including infections and access failures. And Prabir, I was wondering, could you comment on what we're seeing here?

Yes. No, thanks, Laura. So I will say the first time that I saw these slides, 1 thing absolutely hit me and sprang out of the slides. And that is that in vascular access, it's very clear that a one-size-fits-all approach is not going to work. It's not going to work in vascular access. It doesn't work in medicine as a whole. It doesn't work in life in general. And so I think what we clearly need based on the clinical experience that's out there based on the data that Laura shared with us is that we need an individualized precision medicine approach, if you will, for vascular access. And I very strongly believe that if we have different therapeutic options, that will allow us to have this precision medicine-based approach, because there will be device A, for example, for this patient population, device B, perhaps or another patient population. And the reason that this is so important is not just in terms of better care and reduced complications, but this is the way that we're actually going to be able to reduce health care utilization. This is by fitting the device to the patient, we're going to be able to reduce hospitalizations. As Laura showed in the previous slide, this huge increase in hospitalization rates in women, and hospitalizations is totally key because the whole kidney community is moving now towards a more global payment system. And so the reduction of hospitalization is going to be absolutely key in terms of the economic model that's being built around kidney care. There's 1 other really important point that I think comes out from everything that's been said. And I just want to emphasize this once again. It's really important that the fruits of innovation, the fruits of our innovation actually reduce disparities in care as opposed to enhancing them. And unfortunately, what often happens is that we have this wonderful innovation, but it actually enhances disparities in care because it's available to 1 group of people or works in 1 group of people. And I really believe that the future use of the HAV in women, in particular, could be a great example of how innovation could actually reduce disparities in care, all the disparities that Laura and Timmy have described to you. I want to come back at the end, Laura, and this is a long comment. I apologize to it, but I appreciate this opportunity. I just wanted to come back to the patient I spoke about. So that was 20 years ago. I was rounding on our general kidney service about 3 months ago. I had 20 patients, 3 of them had infective endocarditis, were in hospital following cardiothoracic surgery, because their valves had got infected. This, again, I just want to put out to you, I think this is unacceptable in 2024, particularly when we've known that this happens for the last 25 years, and we absolutely need to do better. So I'm definitely going to be watching this space, Laura, and we're very excited about the future. So I'll hand back to you.

Thank you so much. If we could go to the next slide, please. I think we're going to ask Dr. Lee to talk about some of the economic implications of the complications in dialysis access. Next slide.

Thank you. So I have the next 2 slides, and I think this really kind of is a good segue to talk about economics and how failure of our dialysis access and issues, in particular use of catheters, impacts this. So I want to put next 2 slides in context. It's not on this particular slide. So Medicare is the largest provider for patients in terms of services for kidney care as well as dialysis access. And in this particular regard, we have about 700,000 to 750,000 patients in the end-stage kidney disease program in the United States. So among these -- in the overall context here, we spent over $50 billion taking care of end-stage kidney disease patients and the large majority of them utilize hemodialysis. So in that perspective, we spend about 8% of the entire Medicare budget on taking care of about 700,000 end-stage kidney disease patients. So you can see -- and a large part of this is dialysis vascular access. So I want to put that in context before I talk about this slide. So a group of us in the mid-2010 decade wanted to understand the economic impact of dialysis vascular access and that had been looked at in over 20 years and previously published by Hart Feldman. So what we did is we took USRDS data. So USRDS is the national registry for all dialysis patients funded by Medicare in the United States, and we linked it to Medicare data. So 1 of the things we wanted to look at is the overall cost that Medicare and this particular subset is looking at patients, elderly patients over age -- 66 years of age. So 1 of the things we wanted to look at is in terms of dialysis vascular access, what are we spending Medicare cost on? And in summary, if you look at this slide, they the large majority of costs in the years 2011, 2012 and 2013, are being spent on, first of all, invasive imaging endovascular procedures. So these are procedures being spent to evaluate and to fix dysfunctional vascular accesses. So almost 40% of costs are being spent there. The other large cost being spent is on inpatient costs related to hospitalizations from catheter infections. As you can see, $1.5 billion being spent over the course of -- in each year, from 2011, 2012 and 2013 on inpatient admissions. So in summary, if you look at the years 2011, 2012 and 2013, it's pretty consistent, spending about $2.8 billion annually for vascular access related services. Next slide, please. So in this context, and this particular publication that we had, we wanted to look at 3 particular cohorts in 3 particular scenarios for patients that start dialysis. So in cohort #1, this is a common scenario, as patients who have a fistula that's placed predialysis and successfully matures to be able to be cannulated in first dialysis, that's cohort 1. Cohort 2, this is also very commonly seen as well, too. They had a predialysis vascular access, but it's not ready to be used on their first dialysis and they initiate with a tunneled dialysis catheter. And then Cohort 3, which is probably the most common scenario that we see is that a patient predialysis has no access placed fistula or graft and initiate with a hemodialysis -- dialysis catheter. So we wanted to look at several different outcomes and its relationship with the economics and costs first, that is whether or not a patient maintains primary patency in the first year. That means that they had required no intervention after the fistula was created in the first year, whether or not they lost primary patency. So in the first year, meaning did they require some kind of surgical or endovascular intervention to maintain access patency? And then the third outcome we wanted to look at is that whether or not the fistula was abandoned, meaning secondary patency loss in the first year and its economic cost. And then finally, whether or not the fistula was ever successfully used. So in cohort 1, that was defined as whether or not we had a code, a V code, that's a monthly code registered for the type of access that's used every single month and cohort 1 was whether a V code for a fistula identified in months 1 to 3. In Cohort 2, that's whether or not a fistula code was identified in months 1 through 5. In Cohort 3, that's -- was a fistula code identified 6 months after a fistula creation. So to summarize these particular results. I think the most important being -- several important components here. When your fistula is never used, and this is across the board here, if you look at this outcome compared to the other ones, it's really, really expensive. For example, if you look at Cohort 2, $55,000 per patient in year 1 if the fistula is never used. In comparison, once the fistula is used, if you maintain primary patency, patients that maintain primary patency, that means they did not require any interventions in the first year, the cost is much less. But also, if you look at -- lose primary patency, again, if you begin intervening in an access, the cost per patient increased significantly. So what I want to say is that failure of a maturation is estimated to be over 30,000 in the first year. And the theme of this particular, this particular seminar as well is that women are much likely to fail, to have ABF maturation failure than men. So I think it's really critically important economically as well, as well as in terms of processes of care that we address these access options for our women. Back to you, Laura.

Yes. Thank you so much. Just returning now to some of the Frenova data after this background that was provided by Dr. Lee, if we look at some of the cost information that was extracted from Frenova's database, again, looking at the time period from 2016 to 2021, we see some really kind of startling and impressive differences in cost of access care, depending on whether or not a patient has a successful access versus not. So in this analysis, this was examined not so much by demographics, but looking at the entire dialysis population overall. And then dividing the cost of access care. Again, this is not including the cost of hemodialysis. This is not including other complications. This is just cost related to placement of the access and maintenance and complications with the access. If we look at the bottom quintile of patients, the least expensive 20% of patients in the Frenova database, we see that their costs for access care range from 0 to about $6,700. In the middle of this distribution, annual cost of access care ranged from $21,000 to $44,000. But the upper quintile of dialysis access care can range from $91,000 to over $155,000 per year in patients who are followed in the Frenova system. And this goes along with substantially higher annual complication rates in per patient per year in this top quintile ranging from 4.7 to over 13 access complications per year. So as Humacyte has always discussed with our key stakeholders, we believe that the HAV has the potential to provide real benefit for dialysis patients, particularly patients who are burdened with high rates of complications, which are both deleterious for quality of life and also incredibly expensive to the health care system. And this quantification of costs I think, is impressive for us and it's impressive for other people who have participated in this analysis and really point to the fact that if the HAV can reduce complications in complication-burdened patients, that the savings to the health care system can be substantial in addition to improvements in quality of life. Next slide. So if we look at patients who have survived for less than 1 year on dialysis. This is a subset analysis of the cost study that was -- I described in the next slide. If we focus on patients who survived less than a 1 year on dialysis and look at their overall cost of care, we see that there are subgroups within that patient population that really is to focus on women and particular women who may have burdens of diabetes and obesity. And what we can see is that in -- this is just an example of 1 subset population that we have many other outcomes here in different population subsets. This is just an example. If we look at women who are less than 65 years old, but who are also obese and diabetic, which is 6% of the overall dialysis population, we see that those patients on average cost the system an excess of $91,000 per patient per year. So it is possible, using these types of analytic approaches, to identify really specific demographics that are burdened with high complication rates and also very high costs. Next slide. So overall, summarizing the work that we've done between Humacyte and Frenova and also some of the insights that were provided by our key opinion leaders. As we've mentioned, women are much more likely to be burdened with grafts and catheters as compared to men. These types of access have higher complication rates. And these complication rates are associated directly with higher cost of care for maintaining their access. We know from data that was published a number of years ago, that aside from men and women, we know that if a fistula fails that, that costs Medicare more than $30,000 in the first year. And so identifying patients who are likely to have a fistula failure and providing them with another form of access that also resists infection could be a huge benefit to the system. And as again, as I showed in the last slide, specific female subsets are at particularly high risk and we just showed 1 particular example in the prior slide. Next slide. So I'd like to turn this back now to our Chief Medical Officer, Dr. Parikh, who's going to walk you through a trial that we've just initiated that we're very excited about that we think will really help to highlight and quantify the benefits of the HAV in these female high-risk subgroups. Next slide.

Thank you, Dr. Niklason. So yes, it's been shown and proven today based on what you have heard that female patients need better AV access options. And it is clear that HAV, based on its profile, has advantages over AV fistulas, both in terms of time required for maturation and also removal of CVCs earlier, so there is less risk of infection. The V007 trial, which we'll report out later this year, includes both men and women. Women comprise of 27% of the cohort. So we will be looking at this cohort very carefully to see the performance of HAV versus AVF. But we need to study this holistically. In 007, we had single-stage AVF maturation patients being enrolled. We have, therefore, launched a V012 study. This is the only study of its type that is a women-only study that will collect comprehensive data on outcomes and complications in women receiving HAV versus AVF. In this study, patients who are candidates for both 1- and 2-stage AVF are included and data on AV access function as well as health economic factors and socioeconomic factors are being collected. So what does this study look like, in the next slide. Essentially, V012, our HUMAXX study is a trial comparing Humacyte's HAV versus AVF in women. This is a trial -- it's a superiority study that is looking at a unique endpoint that is looking at catheter-free days. In other words, it's looking at how many days are patients able to stay-off of catheters if used an HAV versus AVF. It's also a trial that is actually looking at women who are candidates for AVF. So it's very balanced from that perspective. And both Stage 1 and Stage 2 AVF patients will be randomized. It's a one-to-one study, and as I mentioned, it's a superiority study of HAV versus AVF. The primary endpoint will be evaluated at 12 months. We do have a 24-month follow-up in this study. We will look at infection rates as well as interventions required for HAV versus AVF in this trial. This study has started recruiting last year, about 20 sites in the U.S. are open and are currently recruiting women in this trial. So with this, to put this trial into perspective, let me turn it back to Dr. Niklason.

Yes, if we could go to the next slide. So I think the V012 trial will have tremendous strategic value for Humacyte in terms of really quantifying the particular benefit that the HAV, we believe, will provide in women, both clinical benefit and health economic benefit. This trial was designed in consultation with nephrologists and also in consultation with the FDA. And the FDA acknowledges that women are an underserved population in dialysis and dialysis access care. I know that we're running a little bit late, and so I would like to open up the forum for questions, if we could, because I want to make sure we take at least a few questions before we have to close the session.

[Operator Instructions] So our first question comes from Josh Jennings at Cowen.

Thanks to the Humacyte team for this presentation and sharing all these analysis. I wanted to ask, Laura, just in terms of the agreement with Fresenius and to adopt HAV as a standard of care for its dialysis subgroup patients that were -- there's proven to be a benefit in the clinical trials. Can you just remind us of that agreement. And I guess the second part of the question, is just thinking about 43% of women in the U.S. dialysis patient population in African-American dialysis population, but [ it gets ] the kind of overall number of the 2 big subjects you guys are talking about today, over 50%. But should we be thinking about HAV being indicated for well north of 50% of the overall U.S. dialysis population, ultimately?

Yes. Thank you, Josh. So yes, I'd like to highlight both of those statements. So our agreement with Fresenius is that in the United States, they will adopt the HAV as standard of care in their clinical practice where the HAV -- data support both the clinical benefit and the health economic benefit of the HAV. And again, based on the data that we've shown here, we have a strong expectation that the data in women will be very powerful, both clinically and on a health economic standpoint. And you're right. I mean if you add up African-Americans plus women, that's well north of 50% of the entire U.S. dialysis population. Next question.

Maybe just 1 more follow-up, if that's okay. What is -- I mean, just in terms of the female population and any signals you can share from any of the Phase II studies, may access or V006. It seems like in V007, there was a -- as minority of the patients were female, and that may be the case for earlier studies as well. But any studies -- any clinical signals you guys have found in the earlier data that has accrued. It would be great to hear.

es. So we haven't shared previously signals on -- gender-specific signals from V006 or from our Phase II studies. We're planning to share those going forward. I would say that in V007, the -- in prior studies, the enrollment of women and men was roughly at par in our prior studies. In V007, because of the way this -- the trial was designed, it was limited to a single-stage fistula, which is a specific. It's about half of the fistula operations that are done. But many practitioners believe that's -- have an apprehension about using single-stage fistulas in women because their maturation rate can be very low. And so we wound up under-enrolling women in V007 with only 27%, we believe because of that limitation around single-stage fistulas. So by doing the V012 trial, which is a smaller trial, we're doing an interim analysis at only 80 patients. But by opening it up and by allowing both single stage and 2-stage operations, we believe that we're going to capture the entire female cohort and really nail down the benefits of the HAV.

Our next question comes from Bruce Jackson of Benchmark.

Thank you for the really informative presentation. I wanted to ask a follow-up question about just general market adoption. So to what extent do you think you need to have the V012 results to get greater acceptance in the female population? And will that be enough to get it kind of to become the first-line standard of care treatment for the female population?

Well, it's -- not knowing what V007 is going to show, it's hard for Humacyte to make predictions on that score, Bruce. But I would say that given that women were relatively under-enrolled in V007, augmenting that total dataset with V012, we think will really strengthen both the clinical and the health economic arguments around the value of the HAV, particularly in women. As our KOLs noted, Medicare is really the single payer in the dialysis access space. and showing that the HAV provides clinical and economic benefit for women showing that to Medicare, we think, will be a huge supporter for reimbursement for these patients.

Okay. Great. And then when might we get some results out of the V012 trial that we can see?

I'm going to defer that question to Dr. Parikh.

Yes. We anticipate completion of enrollment required for analysis by first quarter next year. And within 1 year, we expect results for V012 to be available.

Our next question comes from Rick Miller at Cantor.

This is Rick on for Kristen Kluska. And just 1 question from us. Perhaps a question for the guest speakers that you had on. How are you thinking about how the durability of HAV could stack up against fistula? What are the common problems with long-lasting fistulas? And what signals will you be looking for in Phase III data to kind of get a better understanding of whether HAV is an improvement in terms of long-term durability?

I think Timmy or Mike or Prabir, I think any of you guys would be good for this answer. Mike, do you want to go?

Sure. So just to clarify the question, you're asking about durability of the HAV?

Yes. As it relates to fistula -- versus fistula?

I think that's what the 007 study is looking at, a direct head-to-head comparison of fistula versus graft. And I think we should have some direct head-to-head comparison in that from that data. With regards to my experience, we enrolled, I think, over 13 or so patients, who got the HAV in the comparison study between the grafts, the 2 types of grafts. And I noted that the HAV, I still have patients I see every day that are now 6 years out, 7 years out from that implantation doing well with the HAV. I found it to be exceptionally durable in comparison to the PTFE grafts. So I think it will probably be closer to what we see in a fistula. And if it has the additional benefit of avoiding creation of fistulas that don't work or don't mature or require a lot of work to maintain maturation or patency, then I think that's kind of a home run. I think in a certain subset of patients that we haven't been discussing here in the older patients, we've really been kind of moving away from fistula-first concept that was really popularized almost 2 decades ago now, and have been going more towards primary graft placement in the elderly because of all the challenges you've heard from our 2 nephrologists here with patients having prolonged catheter use in the frail patients and getting that catheter out and getting them an access that works quickly, I think, is a huge benefit. We've been doing that with just the standard PTFE graphs now for a while. And I think that's going to be a big switch to using the HAV if it becomes available soon for those particular patients as well, the elderly patients who we are now really going towards graft first rather than fistula first.

Okay. Anybody else needs to add?

Yes. Laura, if I can -- both Laura -- and both Timmy and I. So I was just going to make a comment saying that, of course, durability is important. But as a clinician, the biggest problems we see really are the ones associated with catheter infections because your fistula hasn't matured or because you've just had the catheter in for a very long period of time. And I think that the benefit that could come from a device like the HAV that allows catheters to be removed more quickly and at the same time, it doesn't have the infection rate potentially of PTFE grafts. I think would be huge, both in terms of quality of life, from the patient perspective and obviously, at the economic level. Timmy, go ahead.

So I'll just add to that. I mean, Dr. Curi gave a really, really nice answer. So there's a new set of KDOQI guidelines that were published in 2019. A group of us worked on that. And we're getting away from the fistula-first concept, and the main theme is the right access for the right patient and for the right reason at the right time. So a more patient-centric approach. So as Dr. Curi mentioned, I think there is more latitude these days for putting the right access in the right patient. And also on the economic level, I'll [ quote ] from CMS, I think, beginning in 2025, that monthly metric to see how many fistulas you have in your unit will be going away. We will not be judged on anymore -- one of the main metrics we'll be judged on is the number of catheters. So I think that is a good thing, allowing more flexibility in terms of vascular access options.

I would just say that, that's going to really drive things towards doing these correct or more appropriate access creations. There was a -- it was ingrained into all vascular surgeons training for about 20 years that you have to try to do a fistula in everybody you can. And that's so 1990s at this point. It's people who are doing a lot of access really know that those patients that we try to do fistulas in, that really struggle with it wind up having bad clinical outcomes. And so we're moving away from that. It's just a matter of getting a better conduit to create the grafts. And I think this is where this HAV may be a game changer.

Tara, do we have another question from 1 of our analysts?

Yes, we do. So our next question comes from Izzy McMahon at BTIG.

[indiscernible] more towards you. And I recognize a little bit on the early end for this, but do you have any estimates on the specific savings that the HAV may produce within these populations given the massive burden that we're seeing for the system so far?

Yes, Izzy, thank you for the question. You're right. It is a little bit early and I really hesitate to speculate. I do think that just looking at some of the cost numbers that we've shown here from the literature and from the Frenova data, it's easy to imagine that the cost for the failed fistula could be $30,000 or substantially higher than that. And the cost of a complication burdened access, meaning, for example, a catheter that suffers multiple infections, that can easily run north of $50,000, $60,000, $70,000. When you look at those numbers associated with catheter complications and fistula failure, just on a pure economic basis, the HAV becomes a very affordable option.

So Laura, it looks like there's no more questions from our analysts. I'll now turn it back over to you to read any written questions.

Yes. Thank you, Tara. So we have a number of written questions. We actually have a large number. One of the written questions asks us to speculate about the asking price, the ASP, the average selling price for the HAV. Again, as we've let our investors and our analysts and our stakeholders know, of course, the anticipated price for the HAV has not been set. However, in some of our prior SEC filings, we have provided estimates of ASP in the area of $25,000, which we think is a price that will be supported by health economics, not only in the trauma indication, which we anticipate will be our first indication, but based on these data, also in the subset of dialysis patients who have trouble with the dialysis access. Just looking through some of the other written questions. We have, we have 1 question from Piper Sandler. That's a written question for the key opinion leaders. And the question says, what type of clinical profile would you need to see for the HAV and V007 to have it broadly used? Is superiority to fistulas or functional patency at 6 months or 12 months necessary, or is noninferiority enough? And I think this is a question asking about the overall dialysis patient population. But perhaps Dr. Curi, if you could comment again on what you might see in V007 that would support your use of the HAV either broadly in dialysis or for a subgroup of patients, I think that would be helpful.

Yes. I think that's a great question. And I think it comes out to the crux of the issue. There's 2 things we look at. One is the durability or patency of an access. But then we also look at the maturation rate. So these are 2 separate metrics that we look at. And if we think about fistulas where, in females, the fistula maturation rate may be 50% to 60%. That means that there is a 30% to 40% to 50% of patients who have surgery that does not lead to a usable access, and then they wind up needing some other access created, creating these delays, creating extra -- significant additional costs as was outlined earlier. Then you look at patency. And by the way, with regard to maturation, the primary failure of these grafts are very low. So we're talking about a primary failure rate of 40% in the nonmaturation of a fistula versus a failure rate of 2% to 3% for a graft as a primary failure. So the -- then there's the secondary outcomes of patency or durability. And I think that if you have a large difference in maturation or functional use capability in that primary failure, then I think that secondary outcome of patency is just that -- is that it's a secondary outcome. So for me, the primary benefit of this is in using it in patients that we know are relatively high risk for fistula failure, so if there's a significant difference that we see in that study, it's going to be a primary access choice for us in patients who we think are likely to fail fistula.

Thank you for that, Mike. Looking through the other questions here, I'm not seeing a lot of questions that I think are more broadly applicable. There are 2 specific questions. One is, how soon can the HAV be used for access after implantation? And our current guidelines in our clinical trials is 4 weeks. Four weeks after implant, the HAV can be accessed. We also had a question asking, have we studied the HAV as an access in the lower limb, in the femoral circulation? And the answer is no. We have not studied the HAV there. We've only studied the HAV as access in the upper extremity, although our other clinical indications in PAD and trauma have seen a lot of use of the HAV in the lower extremity. I think looking through the written questions and if there -- I think that's -- that we've covered it. And if there are no more questions from our analysts, Tara, I think we may be done here.

All right. Great. Yes. So any closing remarks, Laura?

I would just like to really thank our key opinion leaders, Dr. Lee, Dr. Roy-Chaudhury, and Dr. Curi. All of these men obviously have decades of experience in caring for patients with kidney failure and their accesses and they speak from direct firsthand knowledge of what they see every day in the clinic. Their observations align very closely with the huge database that we were able to access with our partner, Fresenius. And so it's always nice when all the data points line up, and I really look forward to seeing the results of our V007 trial and also this focused V012 trial in women, because I really believe that the benefits of the HAV particularly in high-risk dialysis patients are just going to get clearer and clearer and more and more compelling. And so with that, I think we can close. So thank you, Tara, and to LifeSci for hosting this, and I hope everyone enjoys their morning.