Good morning, welcome to the Humacyte Virtual Webinar. At this time, all attendees are in a listen-only mode. A question and answer session will follow the formal presentations. 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 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 welcome everyone to Humacyte Virtual Webinar, describing the current unmet needs in dialysis access for patients who have kidney failure. As many of you know, we've been engaged in a phase III program looking at the safety and the efficacy of Humacyte's acellular tissue engineered vessel or ATEV, in its function as a access for hemodialysis, and specifically comparing this access to patients who receive the current gold standard, which is fistula. Next slide, please. These are just our disclaimers. Next slide. As you'll see from this program, you're going to hear from two important key opinion leaders discussing about the current unmet medical need and the current shortcomings of hemodialysis access and how Humacyte's ATEV may be able to benefit some patients.
The first speaker will be Dr. Prabir Roy-Chaudhury, who is the co-director of the UNC Kidney Center and who is an eminent professor of nephrology at the University of North Carolina. Importantly, Dr. Roy-Chaudhury is also the immediate past President of the American Society of Nephrology and has a broad view on the current challenges that are presented to many dialysis patients in the United States. After that, you'll hear from Dr. Mohamad A. Hussain. He's an associate professor, I believe, at the Brigham and Women's Hospital in Boston, and he is a vascular and an endovascular surgeon and has participated in several of Humacyte's clinical trials studying the safety and efficacy of ATEV compared to fistula in patients with kidney failure.
After the presentation from these two speakers, you'll then hear from our Chief Medical Officer, Dr. Shamik Parikh, who will give you a little preview of the current phase III trial that we're running comparing the ATEV to fistula, particularly in women who suffer kidney failure and who are on hemodialysis. After that, we'll have time for question. With that, I'm going to turn it over to Dr. Roy-Chaudhury.
Great. Thanks so much. I'm gonna start off by saying that I'm a nephrologist, as Laura said, which is that for the last 25 years of my professional life, I have taken care of patients on hemodialysis. My charge, as I see it over the next 10 to 15 minutes, is to speak to you about the why. Why we need the ATEV, why we need to do better as a kidney community, and why I believe that the ATEV could actually make a difference in the quality of lives of patients. With that, let's talk a little bit about vascular access. We have 550,000 patients currently in the U.S. who are on dialysis.
If you're on dialysis, I should say hemodialysis, you need to have some form of dialysis vascular access so that the nurses and the physicians get access to the blood purified in the back end. The vascular access is truly for these half a million plus patients on hemodialysis. It is also unfortunately Achilles' heel of hemodialysis, and this slide tells you why. Main forms of dialysis vascular access, the arteriovenous fistula, the tunneled dialysis catheter, and then synthetic grafts. The gold standard, although it isn't really a gold standard at this moment, is the arteriovenous fistula. Currently, in 2025, if you place 100, or if Dr. Hussain, I should say, places 100 new arteriovenous fistulae in dialysis patients, about 45 million without a problem, which means.
Dr. Roy-Chaudhury, I'm so sorry to interrupt.
Yes.
At least for me, the audio is a little choppy. I'm wondering if you can go off camera and that may help the bandwidth.
Okay. How about now? Is that better?
It's better.
Okay. My apologies. Okay. If we were saying that if Dr. Hussain puts in 100 arteriovenous fistulae, about 40 will actually function without a problem, which I think is actually in 2025 for a vascular access procedure. Remember, gold standard, although it's actually been unchanged, if you will, for the last 50 years. The problem that happens when a fistula doesn't mature is that in our current process of care, 80% of new hemodialysis patients actually start with a tunneled dialysis catheter. We then place fistula, which means that if the fistula does mature quickly or fistula fails, you're going to have a long time, if I may pardon, with a catheter. You're going to have a prolonged catheter contact time.
To me, that is one of the worst things that can happen in the world because if you have a prolonged catheter contact time, you have the complications of catheters, infection, thrombosis, central vein stenosis. Most importantly, I would say infection, infection, which results in ICU admissions, hospitalizations, and a huge increase in cost. Which is why, particularly in older patients, if you dialyze a patient for a year with a dialysis catheter, the cost is only $100,000 a year. If you can dialyze that same patient through fistula, then that is down to about $120,000 in older patients.
Huge savings, and these savings, again, in my mind, particularly through the work that we've done in the American Society of Nephrology could actually be very important in global payment systems, such as the Comprehensive Kidney Care Contracting models and other such patients, where, in reduce up initial costs, you're actually going to end up with a significant cost savings. Let's, let's move on a little bit more in depth. Who are the people who actually end up with a catheter, and who are the people who actually have complications with a fistula? This is data from the United States Renal Data System.
What it shows is that if the 100 patient, if you 100 patients starting dialysis with a tunneled dialysis catheter, and remember, I said earlier that if you have 100 patients starting dialysis, 80 of them will start with a catheter. This is the vast majority of patients start with a catheter. Sorry, I beg your pardon. Which means that the vast majority of patients starting hemodialysis with a catheter. Even out at six months, if you're a male, 50% of patients still have a catheter. If you are a woman, that is actually a lot more. You have 54%, and that number continues to be high as you go down to nine and to 12 months. The next question, of course, is: Why do women have an increased incidence of catheters?
The answer comes back to the fact that women are the phenotype where your arteriovenous fistula is actually not going to mature well. The reason for that is that these fistulae, these connections between the artery and vein, actually fail because you have small arteries and smaller veins. Women, of course, do have smaller arteries and smaller veins as compared to men. If you think a bit further, what I've spoken about till now are the people or the patients who are new to hemodialysis. If you look at 100 patients who've been on dialysis for a long period of time, you still have more women on a catheter, about 30%, as compared to 24%.
Both for incident hemodialysis patients and for prevalent hemodialysis patients, you have more women on catheters, you have fewer women with a fistula, which is the goal of preventing complications and for reducing costs. Finally, if I go on to my penultimate slide, I believe, I just want to, as a physician, say that catheters are, in a way, evil. I think catheters are often described as the white tube of death. I just want to emphasize that, yes, you can say that they cause infection, thrombosis, and central venous access dysfunction. You can say that they cost a lot of money. I would say that most importantly, catheters destroy the quality of life of our patients. In summary, what I want to emphasize is that around 80% of our dialysis patients start with a catheter.
Where arteriovenous fistulae are placed, it takes many months for the fistula to work. The people, the patients who suffer the brunt more than anything else of failed fistulae or fistulae that fail to mature are actually women, which results, as you can see on this slide, in a higher mortality and all the bad outcomes in terms of infection, stenosis, and thrombosis that I spoke about. That's why I'm so excited about the potential of the ATEV to be placed in women instead of an AV fistula, so that we can target all of these complications and problems. I want to end just as I started, as a clinical nephrologist. This is a patient story that is absolutely true. It was about 15 years ago. I do a lot of transplant work, and I remember seeing this 28-year-old Black female.
She was tall, and she came with, and they had just got married. She had ESKD, and she had a catheter in place. As a transplant nephrologist, I remember spending a lot of time talking to her that, you know, we can give you a normal life if we can get you to a transplant. You can work, you can have children. I was really positive about it because she had a living donor. What I had not taken into consideration at that point in time is that she had a tunneled dialysis catheter and that she was a woman. That combination changed everything for the worse. The next time I saw her at the vascular access clinic, she was paraplegic, so she couldn't move her lower. What had happened was that she had had a fistula placed.
It didn't work. She had a prolonged duration of catheter exposure. The catheter got infected. The bacteria from that infection seeded her heart valve, she had an embolus that went off to her spine that resulted in spinal cord compression. The tragedy is that my 25 years as a nephrologist, these problems stayed the same. I'm going to end really, I really hope that we can do better. I do believe, depending on the results, of course, but I'm excited about Mohamad's presentation, Shamik's presentation, that the ATEV actually allows to improve our patients' quality of life at a reduced cost by reducing catheter contact time. With that, thank you for your attention, I will hand over to you, Mohamad.
Good morning, everybody. Thank you so much. It's really a pleasure being here, and thank you, Dr. Roy-Chaudhury, for setting that up so nicely. I am a vascular surgeon at the Brigham and Women's Hospital and Harvard Medical School in Boston. I've had good experience using the ATEV as we've been participating in Humacyte's for randomized controlled trials because, like Dr. Roy-Chaudhury said, we feel that there's a big unmet need for these patients. Today, I'll specifically be talking to you about results from the V007 randomized controlled trial, focusing on the female subgroup. As we heard, AV fistulas are generally the preferred initial access for hemodialysis according to our national guidelines. There's a big problem. These fistulas do not mature well, especially for women with small blood vessels.
ATEV is a promising alternative vascular access, as we've heard about, and it has shown durability and low infection risk, which is very important to me as a surgeon as well as for our patients. The analysis I'm presenting to you today is a two-year outcome analysis from the V007 randomized controlled phase III trial that compared ATEV with autologous AV fistulas in hemodialysis patients in the subgroup of women who were enrolled in this trial. Here's the study design. This was a prospective multi-center randomized controlled trial across 31 centers in the U.S. with broad representation. 242 patients were enrolled in the trial. All of these patients had end-stage kidney disease. They were on hemodialysis with a tunneled dialysis catheter, and they were eligible for both an AV fistula creation or an AV graft creation.
They were randomized one to one to receive either the ATEV or AV fistula. All of these patients were followed for two years. The key inclusion criteria were as follows. These were adults with ESKD on dialysis who were eligible for either AV fistula or AV graft and were expected to live longer than two years. The key exclusion criteria were that patients who were candidates for the perfect optimal fistula in the hand or distal forearm were excluded, which is not very common. Patients who had uncontrolled diabetes were also excluded, and importantly, patients who would need a two-stage access were also excluded. Let me put that in context. Many patients, if they have small blood vessels, we often need to do two surgeries to give them a usable fistula, which could take several more months to mature and get ready for use.
Often, these are women, and these particular high-risk subgroup were excluded who would otherwise get a fistula. Here are the key primary endpoints. The primary endpoints was a combination of functional patency at six months, which was defined as two needle cannulation in the dialysis unit for four weeks, and secondary patency at 12 months, which is a measure of durability. Key secondary outcomes included duration of usability of the access over one year and two years, as well as interventions over the first two years. Safety outcomes included infection and other adverse events. This was a subgroup of patients in the overall trial. You can see mean age was around 57 to 60 in both groups, and about a third were over the age of 65. Female subgroup, which we will focus on, in the next slides, was about 30% in both groups.
About 40% were obese in the ATEV group, and 35% were obese in the AV fistula group. Two-thirds of the patients were diabetic, which is in line with our expectations. You can see patients already had the catheters in for three to four months by the time they even enrolled in the study. Here's the primary outcome in the overall trial, so all patients. You can see the trial was positive with functional patency 81% in ATEV and only 66% in AV fistula. Secondary patency 67% in ATEV and 62% in AV fistula. This is a number I'd like for you to remember, the secondary patency, as we move on to the women subgroup.
Overall, the P value was 0.009, with a joint relative patency of 1.17 in favor of ATEV over AV fistula for all patients in the trial. This benefit of ATEV was really amplified in the women subgroup. You can see the functional patency in women was 89% for the ATEV group and 54% in the AV fistula group. The secondary patency was also now dramatically different, 81% in the ATEV group and 48% in the AV fistula group, with a P value of less than 0.0001 or joint relative patency of 1.65 or 65% improvement in outcomes in the female subgroup with ATEV compared with AV fistulas.
There was a larger ATEV benefit for females with respect to usability of the access over the first two years. You can see the first bar graph represents all randomized patients. Purple is AV fistula and dark blue is ATEV. You can see AV fistula was used about 12 months of the first two years, whereas ATEV was used about 13 months from the first two years. The difference was significant when you look at the female subgroup. In the female subgroup, because of high risk anatomy in patients, AV fistula was only used about 10 months, whereas ATEV was used about 15 months with a P value of 0.0137, a significant difference. Patients who received the ATEV also matured earlier at a higher rate. The first graph on the left shows median time to maturation.
You can see in all randomized patients, fistulas take about three-four months to mature, which is in line with our expectations. ATEV can be used much quicker, between five-six weeks. Again, the difference is amplified in the female subgroup. Females, it takes much longer for their fistulas to mature. In the trial, it took about four and half months. ATEV recipients, the access was usable within five-six weeks. The maturation rate was also higher in the ATEV group. All randomized patients, about 69% used their fistula that matured, whereas this number was 84% in the ATEV group. When you look at the female subgroup, again, the difference is amplified with only 55% of females who received fistulas had their fistula mature, whereas the ATEV was 94%.
Here's a look at the safety outcomes over 24 months. There's a lot of numbers here, I'll break this down for you. One of the most important things to me as a surgeon, again for the patients, is infection, especially when it comes to testing new conduits and new technology in patients. Importantly, graft infections were zero in the ATEV group and zero in the AV fistula group, which is very reassuring and very exciting that this infection rate is very low, similar to AV fistulas in the ATEV group. The rates of thrombosis, stenosis, and pseudoaneurysm were higher with ATEV, as they generally are with non-autogenous conduits. Aneurysms and steal syndromes were very low in both groups, either zero or one.
The second most very important thing, again, to me as a surgeon and for patients, is the rate of rupture when testing these conduits in patients. The rate of rupture was zero in the ATEV group. This is important because you can imagine these patients have their access cannulated with two needles three times a week for years. It was very reassuring to see despite all that cannulation and iatrogenic trauma that we purposely cause, there were zero rates of rupture in the ATEV group. AV fistula, there was only one rupture. Of the thromboses that did occur in the ATEV group, the vast majority were successfully treated. You can see 83% of females who had a thrombotic event was successfully treated with standard vascular techniques.
In summary, in this clinical trial, ATEV outperformed AV fistula in patients who were female and had ESKD. There was superior six-month functional patency, which is usability, as well as durability, which is 12-month secondary patency. In addition, we observed longer duration of successful dialysis over the first two years in the female patients, who received the ATEV. When we look at the safety profile in the trial, there were no infections in the ATEV and AV fistula group. There were fewer maturation and surgical revision procedures required with ATEV compared with AV fistula, but higher rates of thrombosis and stenosis with ATEV, which were successfully treated with most endovascular or open surgical techniques. The key takeaways for ATEV in this trial, it demonstrated meaningful improvements in usability and durability. The access use was faster and more reliable, particularly in the high-risk groups, such as females
There was anticipated decreased prolonged exposure to catheter dependence. Thank you, and I'll turn it over to Dr. Parikh for his slides.
Thank you, Dr. Hussain. Thank you, Dr. Prabir Roy-Chaudhury. I'm gonna talk to you a little bit about our V012 study. This is a phase III study. I'll introduce this study to you. As you have heard from our experts, the reason for doing this study should be quite clear, and it is our way of calling to action and shifting the paradigm by testing if deploying the right access, in this case, the ATEV, for the first time in the right patient, in this case women, helps them in terms of a durable AV access and decreasing catheter exposure. We want to see if this helps shift the fistula-first ideology to a more individualized life plan for choosing the correct AV access for the right patient.
In this study, we directly will be testing the catheter dependence, because we believe that women are, as you have heard, at a higher risk of catheter dependence, and this is a fixable problem. V012 study is ATEV versus AVF in women with end-stage kidney disease. It is a prospective randomized multicenter study with over 25 centers within the U.S. enrolling patients. It's a one-to-one randomization. The clinical trial started in 2023. The goal was to randomize 150 patients, of which we have randomized 126 patients. The key inclusion criteria was women with end-stage kidney disease requiring hemodialysis on a dialysis catheter and requiring an AV access, and then being randomized to either ATEV or AVF. This is a inclusive study.
We are allowing patients who might be candidates for even two-stage AVF to enroll, and the study is stratified based on whether they get an upper arm access or a forearm access, and also based on whether it's a one-stage or two-stage AVF patient in the opinion of the investigator to balance the two treatment arms. The endpoints we are directly testing is the freedom from catheter over 12 months, catheter-free days over a 12-month period, which is a way of testing the durability of the AV access that they get. The primary safety endpoint would be infections through 12 months post-implant. We have a number of secondary endpoints for efficacy and safety, including testing the patency and durability as well as other safety endpoints that Dr. Hussain just went over in the V007 study.
This is a protocol that we have discussed in great detail with the FDA. The protocol is designed with an interim analysis when the first 80 patients complete one year of treatment. We are able to pause and analyze the data. We have reached that milestone recently, where the first 80 patients have completed one year of analysis. Our clinical research organization is now cleaning the data. Once cleaned, we'll be sending it to the independent adjudication committee, who will adjudicate for our key endpoints like catheter-free days, patency, infections, and abandonment of the access. We currently expect results in the 2nd week of June. We do have plans to present the results at the SVS meeting. This is the vascular access meeting in Boston this year on June 11th at a women's forum section.
If we have results earlier, we'll be announcing them earlier, of course, but we do plan on presenting the results at this SVS session. I think with that, I would like to end the formal presentation and would like to see if there are any questions from the audience. Thank you so much.
Great. Thank you, Shamik. Our first question comes from Matt Miksic at Barclays. Please go ahead, Matt. Matt, you might be on mute.
Can you hear me now?
Yes, we can.
Great. Thanks. Thanks so much for taking the questions and appreciate the update. Wondering if maybe you could talk about to both of you or all three of you, I guess, what do you think the process looks like for the clinical community and for centers, you know, to start to uptake these new devices and new approach for AV fistulas, assuming obviously, you know, data comes through, the product's available, what does that process look like? If you could lay that out for us. Thanks.
Dr. Hussain or Dr. Prabir Roy-Chaudhury, please.
I can speak to the surgeon's part, and then maybe others can comment on sort of the process part. I think from a surgeon's point of view, there's not much difference in terms of, we are already used to creating accesses with prosthetic conduit. The technical aspects of the ATEV really are not that unique to a surgeon's usual skill. Usually, you know, an initial conversation to go over any nuances or questions I found, and I've had a chance to speak with other surgeons in the trial, it is adequate for them to be comfortable using the access and describing it, you know, to their patients. I think there might be some additional nuances from the patient or the dialysis unit point of view.
Maybe Dr. Roy-Chaudhury have some comments on that.
Yeah, no. Thank you, Mohamad. I just wanna make sure that you can hear me and see me because I know there were some problems with my audio.
Yes, I can hear you.
Yes, you sound much better.
Okay. I'm sorry. All right. Yes. From a nephrologist, and I would say larger kidney community point of view, the most important thing clinically is trying to get rid of the catheters. You know, both Mohamad and I sort of spoke about, you know, at a morbidity level, at a mortality level, and at a quality of life level, the huge impact that prolonged catheter contact time has on our patients. That vision or that mission has really, I think, translated into our organizational system. You know, every month, as a medical director, you get a printout of the percentage of your patients that are on a fistula, on a graft, and a catheter, and the one that we focus on is the catheter. We focus on that, we focus on trying to reduce the numbers of catheters.
We focus on that because of all the negatives that we've spoken about, but we also focus on that because catheter prevalence is a metric that is increasingly being linked to payment, both in prevalent patients and also in incident patients. To me, what excited me most about Mohamad A. Hussain's presentation and about what Shamik Parikh said was that the endpoints that this study is looking at are catheter-free days. You know, I just cannot emphasize how important that is to the kidney community in terms of quality of life, complications, and payment. Shamik Parikh, or Laura Niklason, do you wanna talk?
I just want. Yeah. I just want to add one thing. We already seen the analysis of the V007 study. Dr. Hussain presented it. That's one clinical trial in women subgroup. This would be the second clinical trial that we are doing exclusively in women. We do anticipate that the two clinical trials, showing good results should have an impact on clinical guidelines because it's very much data-driven. We do expect guidelines which are already talking about individualized access options to look for different access options and to choose the right access option for the right patient. That's another thing that we should be able to achieve, I hope.
That's great. Could I ask just one follow-up, if I could, on, you know, it's great the metric just, you know, that you've described is important. And obviously the clinical benefit is exciting for these patients. Is there anything from a purchasing or a cost adoption that you anticipate will meet some resistance? Or, you know, do you think that the benefit to the center in terms of improving outcomes, improving metrics, is a sufficient motivation to begin adoption generally?
I think Dale or Laura probably is gonna respond to this.
Yeah. I can speak to this a little bit, but then I'd ask Dr. Roy-Chaudhury to also chip in. Certainly, for patients who are at high risk to be stuck on a catheter, to remain on catheter for six or 12 or 18 months, we know that the costs associated with caring for those patients on an annual basis can be $20,000, $30,000, $40,000, $50,000 more than if the catheter were removed. Just from a, you know, a very simplistic cost analysis, the cost of keeping the catheter in, even during the first year well exceeds the cost of placing an ATEV.
I think what these studies are designed to show is that for particular high-risk patients, women, who in some cases have a very low chance of having their fistula mature, there are better clinical outcomes, but also savings to the system. You know, Dr. Prabir Roy-Chaudhury may be able to speak about newer payment models that are being implemented now by Medicare.
Yeah. Yeah, no, thank you, thank you, Laura. Thank you, Shamik. I want to start off by emphasizing one of the things that Shamik said, which is that the kidney community really is excited about moving towards a more individualized and more precision medicine-based approach to vascular access, and that's what our guidelines say. I also want to say that the kidney community as a whole is moving because of the huge costs of care, is moving towards a more global payment system. One of the things that I personally, and I'm wearing my American Society of Nephrology hat here, I'm excited about is that the person who pretty much wrote the kidney executive order, Abe Sutton, is currently the director of CMMI and the deputy administrator for CMS as a whole.
You know, many organizations in the kidney space, including the American Society of Nephrology, and you can blame them actually for the bad connection because I'm sitting in their office in D.C., you know, have really worked hard and have created, you know, connections and pathways to move towards a system where we reduce complications in patients. Again, as Laura said, if you have a global payment system where you get a certain amount of money for taking care of a, let's say, 5,000 dialysis patients, if you can spend $X amount of dollars upstream, ATEV, in order to save $3X dollars downstream, preventing the angioplasties when your fistula fails, preventing the ICU admissions, preventing all the things that happened to my patient, right?
That woman went through a $1 million admission between the time that I saw her with a catheter and when I saw her about three months later in the vascular access clinic. I really do believe we're moving towards that sort of payment system. Remember, End-Stage Kidney Disease patients comprise 1% of the Medicare population, but they use up 7% of Medicare resources. Just recently, for the first time, and we're very proud of that, four people from the kidney community, including somebody from ASN, testified before the chairman of the House Ways and Means Committee. That, I think, is a congressional testimony, just about twp weeks ago that I think is really important for the community.
That's great. Thank you, doctors. Thank you, Dr. Niklason. Super helpful caller.
Great. Thanks for the questions, Matt. Our next question comes from Izzy McMahon at BTIG. Please go ahead, Izzy.
Hi, everyone. Thank you for taking the questions, and thank you for the presentation today. I just wanted to start out, as we think longer term about adoption of the ATEV in these populations, do you think, it will primarily be within these high-risk populations that were highlighted today, or could we see broader applicability across the dialysis population?
Yeah, could I take that, Laura and Shamik?
Yeah, go ahead.
Absolutely. Good question. We are always looking for new therapies that can initially target a high-risk population. As the kidney community gets more experience with these new devices, and in a way, it's not so new, as Mohamad said. This is like a graft that has been used for many, many years. I am very positive about these, this sort of device in particular sort of moving out into other patients. You know, I think a key issue is going to be, you know, the both the ease of placing the device, and then the ease of cannulation. I don't see that any of those are different from normal standard of care.
I just want to emphasize again what Mohamad A. Hussain said in that there were very few infections, and I think that that's really key when compared to other therapies, when compared to the standard of care, which is a graft. I am really positive actually about the potential of this happening.
Yeah. Let me just add this, a couple of points to this. As Dr. Hussain showed, ATEV worked well in across the patients. You know, seven was all comers, males and females. The mean duration used was actually slightly more in ATEV versus AVF in all patients. Lot of significance came from the women's side. Women represent 45% of the population. We look at other high-risk categories. We look at obese males or diabetic males or even elderly patients. Together, this comprises more than two-thirds of all patients who get dialysis. The so-called high-risk group is the majority of dialysis population.
Yeah. If I could add one other thing, maybe this is more of a philosophical or personal point, that is that, you know, in many different areas, we are moving not only towards sort of individualization of care but also trying to see whether women are different. To me, you know, one of the things that is exciting is that, this would really be the first intervention in the vascular access dialysis area that's actually targeting a very large minority of patients where there is actually a biological rationale for doing so, which is small arteries, small veins, poor fistula maturation, increased incidence of catheters. Then at a disparity health equity level, there is a lot of evidence about the fact that women get short-changed in that they are not assessed for fistulae rightly or wrongly.
An intervention like this, I think, could actually make a big difference in vulnerable populations. Not just women, but women in, you know, in deprived areas, inner city areas.
Yeah
... other situations.
No, I think it's a great question. I'll add one more thought. You know, we're only talking about access creation, but from a surgical perspective, there's a lot of patients who have dysfunctional accesses, whether fistulas or grafts. They're high risk because maybe they've had a previous infection or a focal infection. Maybe they're large and they have diabetes and all those risk factors. There is a whole population that the surgeon, when they get comfortable using this vessel, would definitely, I know I would, utilize this for revision or revising accesses that are dysfunctional. I think that will be a natural progression of an additional area that surgeons would consider using this vessel.
That's all really helpful. Thank you. Actually, Dr. Hussain, if I could follow up with you for one question here. You specifically called out the advantages of ATEV for the earlier usability relative to AVF. I was curious, in your practice, how meaningful is the faster time to cannulation, in terms of both the quality of clinical outcomes, but also quality of life for the patients? Does this play a major factor in your decision-making on what to use for these patients? Thanks for the time and all the questions.
Yeah, of course. I think that's a fantastic question. I think, you know, we obviously want to minimize catheter time because of all the things we discussed with catheter issues. Also there's an element of what the patient wants. You know, we focus on the ESKD Life Plan, which is, you know, guiding our therapy that aligns with patient's needs and wants. There are patients who come to us and say, "I want this thing out as quickly as possible." Even though they may have a vein, and you say, "We can create a fistula. It'll take two surgeries and a few months," they'll be like, "Nope.
I just want this out." In those particular patients, I think using a vessel that matures faster and usable quicker definitely is in line with their ESKD Life Plan. I do think the timing does play a large part. It's not the only factor, but it does play a large part in our conversations with the patients to see what's meaningful to them and what would achieve their best outcome consistent with their goals.
Great. Thanks for the questions, Izzy. Our next question comes from RK at H.C. Wainwright. Please go ahead, RK.
Thank you. Thank you, Tara. Thank you, doctors, for spending the hour with us this morning and helping us understand the ATEV. I'm focusing just on couple slides from Dr. Hussain's presentation on the V007 study. If you're looking into the slide that talks about the safety outcomes over 24 months in the females, I know you called out the infections and ruptures, but then when I look at this, there is a, you know, stenosis and thrombosis also which shows up at a higher number compared to the AVF. My question is, was there anything specific about these patients, either, you know, smoking or some other therapies that they're on that's causing this increased number?
Also, would you characterize that certain patients may not be real candidates for ATEV, especially when you have these issues?
Well, thank you. That's a great question. Maybe Shamik want to chime in after too. I think I'll answer it with two points. One is, yes, that's a great question. You know, are there specific factors that are contributing to access thrombosis? My initial response is the sample size was too low in the subgroup. Probably with the larger V012 and combining the data, you know, one could do some subgroup analysis, try to pick up any specific signals to see if there's any particular things that are unique to this population. My second point would be that we know this thrombosis and stenosis is a common issue with any non-autologous access in a patient, whether, you know, it's PTFE that we've been around or other conduits.
The most common area of stenosis happens at the venous connection, so the connection between the conduit and the vein. Not with the artery, but the vein. That's because there's a change in high pressure to low pressure, and there's more shear stress and turbulent flow, and that's a common area of stenosis which leads to thrombosis and leads to, you know, often intervention. That is a problem that is present just like it has been present in other accesses. It was reassuring to see with standard minimally invasive techniques, which usually involves the day procedures where we do endovascular thrombectomy, that the access is revived and the patient can carry on with their use. I don't think, you know, certainly this has not solved the problem, which is present in non-vein conduits.
It's reassuring to see that even though the problem is present, we, you know, it can be treated successfully with stenting maneuvers. Sort of final point, are there particular patients that would not be candidates? There was a requirement to get in a trial that you have to get antiplatelet therapy. If there are patients who, you know, who are not candidates for any antiplatelet therapy because of certain medical history or contraindications, which we know reduces the rate of stenosis and thrombosis, I think those, that particular population, which is probably not that much, it is on to consider not implanting it.
I think the only thing I would add is that the V007 study went on for about six years, and four of those years overlapped with COVID. There was a major disruption, especially in hemodialysis access care during that period of time. Simple things like antiplatelet treatment or even the training that had been given to the staff was disrupted at that time for ATEV, like not using balloon catheters and things. Those are not the issues we have in V012. It would be interesting to see how that incident pans out in V012 study. I think the results will help us understand better what is the difference between the two treatments when it comes to thrombosis and stenosis.
Yeah. If I could just very quickly add, I would say that in general in the kidney community, getting rid of a catheter and preventing ICU admissions, multiple other complications, in general trumps the need for an intervention, which as Mohamad said, is almost always successful.
Thank you. If I may, I can ask a quick second question. Just the following slide where you show, you have shown, Dr. Hussain, that about 83% of these females when they experienced a thrombosis were taken care of successfully. I'm thinking about the other 17% which did not go through successfully. Are there additional things that you as in the physician community can do so that you can increase this number so that you get more of these females back to using the ATEV?
No, I think that's a great question. Again, I think sample sizes were low, so, there's only very few patients in which it was not successful. I think, you know, the key things to think about are as surgeons get more comfortable implanting it, surgeons will get more comfortable picking the right patient, making sure they're on antiplatelet therapy. I think also acknowledging that even if you're not successful in 17% with a thrombectomy, there might be another option that was offered and maybe was leveraged. For example, you can create now a new access around the vein that's developed and the artery that's developed with the ATEV being there for several months.
I think, you know, there's a lot to learn, and I think there is an opportunity to, yes, get that number from 83% hopefully to 100% at some point. You know, that's what we wanna do. We wanna do better for our patients. I think, you know, those things we'll learn as we get the new data from the woman trial.
Perfect. Thank you very much. Thanks for taking all my questions.
Thank you.
Thanks for the questions, RK. Our next question comes from Bruce Jackson at Benchmark. Please go ahead, Bruce.
Hi. Good morning, and thank you for taking my questions. I'd like to know a little bit more about how you think about the decision to use the ATEV. Do you feel there are clear patient selection criteria? Are they similar to the criteria for the clinical trial? Do you need to have guidelines in order for physicians to start using the ATEV? Where does it fit in the, in the sequelae of like which different treatments you select? Could it potentially be the first thing you select? Dr. Hussain mentioned this about the timing could be a factor. That's kind of the generally what I'm trying to get my arms around here.
Do you want me?
Any one of you can start with that question. That'd be great.
Sure. I'm happy to take that first. I currently have a patient scheduled next week, which will be out of the clinical trial, but I'm doing an ATEV because she's a high-risk patient. She had an infection in the contralateral arm for a non-ATEV conduit that needed explantation, and now she needs a new access in the other arm, and I'll be planting an ATEV because being a woman, already had a history of infection on the other side. I think as a surgeon, you know, when you start off, you really wanna include people that were included in the trial because you wanna see if you can produce consistent results with the trial.
I would, you know, patients who I would not include if, you know, if you have that perfect snuff box vein in the hand and, you know, that type of vein might do really well, especially in a patient who's a male and non-diabetic. If I do have a patient like the one I described to you next week, a woman, diabetic and has high risk features, I would definitely consider an ATEV because it performs well. I think surgeons, you know, we would wanna be consistent with the inclusion criteria for the trial starting off. At the same time, you know, people will use it for accesses that are dysfunctional and may need some revision, and maybe it's a little, you know, have had an infection in the past, large arm, so maturation will take a while.
I think, you know, it'll be a combination of using that objective inclusion criteria and a bit of clinical judgment to see the new and the revision access cases that I think will particularly benefit from this vessel.
Yeah. I would just add it's important to be holistic. It's important to look at the whole patient, and I think all of the things that Dr. Hussain spoke about, you know, come into play. I do think that as there is more and more experience, the earlier question was about expanding, you know, indications potentially. I think as we get more and more experience with the ATEV, I think we're going to find more patients who could benefit from them.
Okay. If I could do one more follow-up question. Dr. Roy-Chaudhury shared some data from the U.S. Renal Data System database. There's a subpopulation in there with grafts, 21% I believe. I just wanted to know, what kind of grafts are you using today, and how would you approach that particular subpopulation if you had the ATEV available?
Yeah. The grafts that are generally being used today are standard PTFE grafts. We've used the same grafts I think, for the last 40 years. What I am particularly looking forward to is data that shows that if you use the ATEV in a female population who almost by definition are at high risk for problems with all sorts of vascular access, fistulae and grafts, if we find that the ATEV performs well, I think that is, I think that's hard data that to me would be very important.
Okay, great. Thank you very much for taking my questions.
Great. Thanks for the questions, Bruce. Our next question comes from Charles Wallace at H.C. Wainwright. Please go ahead, Charles.
Hello. Thanks for taking my question and hosting this call. When comparing the V007 and the V012 study, the study populations are a little bit different, and maybe potentially there's room for the ATEV gap to widen. I just wanted to maybe get a better understanding on how you think the benefit will be for the number of catheter days between the ATEV and the AV fistula patients compared to from the V012 study to the V007 study. Thank you.
Well, I think it's a very good question, and I can go over one nuance that's important to me. As I mentioned in the V007 study, two-stage fistulas were excluded. Many patients, they need two surgeries, one to prepare the vein, just do a little connection, and then a second surgery usually about two to three months after when the vein has developed, matured, and to bring it closer to the skin, either because it's too deep or it's not accessible because it's, you know, it's a basilic vein that's developed way and deep in the arm. Those patients were excluded from the first trial. The second trial, the V012 is more pragmatic in that those are fistula patients. Those patients are included, and I think it's a more representation of the real world.
Like, some high-risk patients will need six months and two surgeries to get their fistula usable. I think it'll be a more direct comparison between what's actually happening in the real world in women versus, you know, this ATEV. We don't know the results yet, my anticipation is that the time to using an AV fistula in the control arm would be longer in the control arm in V012. That's my hypothesis, we'll see.
Yeah. I think I would only add that V012 is a very inclusive study for women. You know, in one way it's a study for women, but it's quite inclusive compared to V007. The thinking was, well, of course, it's good to have a big gap from a product perspective, but the thinking was more to see to conduct a very balanced clinical trial, which was in all its facets discussed with the FDA, and they were quite conservative in a number of instructions they provided, which we incorporated. Our goal was to make sure that this is truly represents the clinical population, especially in women, and be inclusive.
We'll look at both maturation time and eventual success rate as two big factors that can perhaps help differentiate and lower catheter dependence on ATEV versus AVF.
Great. Thanks for taking my question.
Great. Thanks for the question, Charles. It looks like that concludes our Q&A session. I'll turn it back over to Laura for quick closing remarks.
Well, I just want to give a huge shout-out to our speakers and Dr. Parikh for really describing the landscape in kidney care, especially for women patients with kidney failure who rely on hemodialysis in order to survive. This is a very complex population, and it's a population that has seen very little genuine innovation, as our speaker said, for decades. I personally am very excited to see the results that we've already generated in the phase III trial, and I'm really excited to see what's going to come in June. I appreciate all of your attention, and I appreciate all of the participants, and I wish you a nice day.