Okay, let's go ahead and get started. Thanks, everyone, for coming. My name is Ally Bratzel, one of the biotech research analysts here at Piper Sandler. And it's my pleasure to introduce Humacyte. So joining us today, we have Laura Niklason, Founder and CEO. And just to go over format, we'll have a couple of minutes of introduction from Laura on the Humacyte ATEV platform, then get into some more detailed Q&A. If anyone in the audience has any questions, feel free to raise your hand, jump in. But with that, Laura, over to you.
Thank you, Ally. It's great to be here. The Piper Sandler Conference is always a terrific conference for us. We've been several years in a row. But yeah, Humacyte is really a first-in-class regenerative medicine company. We have a platform, as Ally mentioned, that allows us to grow human tissues of different shapes and sizes. And these tissues are universally implantable. They can go into any patient without rejection. In fact, we've grown arteries and treated nearly 600 patients now with a range of diseases, and we've never had a single episode of rejection. So our first indication that we're hoping to receive approval for soon is using our engineered arteries to treat traumatic injury, although we have a pipeline of clinical and preclinical stage programs that we're also very excited about.
Great. So yeah, I'll just jump into some Q&A now, starting out with vascular trauma. And the FDA review, as you can imagine, the most frequent questions I get from investors have to do with the review. So here we are, maybe four-ish months since the PDUFA date. No decision communicated. Is there anything new to report on your interactions with the agency?
Yeah, well, there's not much new. So just to recap for people who may not have been following the story closely, we submitted our BLA to the FDA because our vessel is regulated as a biologic. So we submitted it on December 11th of last year. So we're actually coming up on the 12-month date. And the BLA was accepted. We had inspections. We had discussions and negotiations about post-approval commitments. And all of this I've shared before in other phone calls. But we had post-approval commitments. We got way down the track on labeling. And then when the PDUFA date came in August, the FDA said they just needed some more time. And so since that time, and it's been nearly four months now, so we're now nearly at the 12-month point since we submitted the BLA.
We've been pinging them every few weeks and asking them about the timeline, and each time they say that they're progressing in the review, and it could be a couple of weeks, might be a month or two. I really don't have any more granularity than that, but I will say that we have been following through. We had some post-approval commitments just submitting paperwork and validation reports, and we've been submitting those right along, so we've been going along according to the timeline. We're just waiting for them to make a final decision.
Great. So a couple of questions on that. Just have you received any formal written feedback? And I know you said you pinged the FDA. Do you have any levers you can pull to formally request a meeting? I think it would be Type C. I'm not a regulatory expert. But can you pull any of those levers while the review is in this sort of, I don't want to call it limbo stage, but in this?
Yeah, it's a little bit in limbo stage. I think that's fair, and we've had a lot of discussions with our regulatory experts and consultants and even regulatory attorneys about this. I think the communications have been informal to date. Certainly, every time we talk with the FDA, they say that they're making progress. They have not told us anything like, oh, this is a problem. We simply haven't heard that. What we hear is that they're making progress. From our standpoint, I believe that trying to force their hand with this fundamentally new product is maybe not the right approach. I think remaining patient and continuing to work with the agency is the path that we've chosen.
Okay. A couple more on this line. I know there's a lot of other news items to get to. But I'm interested just in the role of the FDA regulators as you've been talking with the agency. Can you just give us a sense of the role of CDRH and kind of what they're doing with the ATEV review? As you mentioned, I think it's long been decided ATEV is regulated as a biologic, but it's very device-like. So just kind of help us understand that dynamic.
I can't say that I understand the internal workings of how the different parts of the agency handle the review. So I simply don't have that information. But what I have shared and what I do know is that the devices branch has acted as a consultant for our application and for the review since the beginning. I mean, we've had surgeons from CDRH sitting in on our meetings for the last decade. So they have been a voice in the review. I also know, and it's public knowledge, that the director of CDRH has turned over, and there has been some turnover in some of the surgical staffing at CDRH. But how that exactly has affected our ongoing review, I just don't know.
Okay. Yeah, I know. Fair enough. It'd be great if we could have some visibility on the.
Yeah, it would. Sure. Yeah.
And then maybe just kind of like last few questions along this line. Your thought that this could be resolved in weeks to a month or two, I guess, what is that sense based on? Is that based on direct feedback from FDA? And then is it your sense that an Adcom or something along those lines is a possible outcome here?
I'll take the second part of the question first. During our back and forth, we have queried about whether or not the agency is interested in an Adcom. And even during the review, we queried them several times, even before the PDUFA date, do you think an Adcom is going to be needed? Every single time we have queried, they have said no. That doesn't mean they won't change their mind tomorrow. But I can tell you they've told us no four times. So that's where that sits. As far as my guessing on the timing, I can't be any more granular than I have been. It could be a couple of weeks, could be a month or two. I've said that I'm aspirational that it's done by the end of the year.
Oftentimes when FDA misses a PDUFA date, they do try to wrap things up by the end of the year, but I can't give that as guidance. It's aspirational.
Okay. That makes sense, and I guess just say you're approved tomorrow. When can you start selling product to customers? How much inventory do you have on hand? What does that all look like?
If we got approval tomorrow, then there is some process that we would have to go through. We'd have to redo the labeling because we would be in possession then of the final label and the packaging and all that kind of stuff. And we would have to repackage and relabel our product and then send that to the FDA and have them sign off on it. So all of that back and forthing, we're guessing, would be about six weeks. We have a stockpile of product now that we could ship tomorrow if we were able to, if we wanted to. So we have a stockpile. So if we got approval tomorrow, then our estimate is that we could ship our first product or start filling orders six weeks after that.
And then just I know you had mentioned discussion on post-marketing requirements. I guess what's your base case assumptions around that? On what kind of post-marketing studies FDA needs? Is it more of like a registry or something maybe lower intensity? Or just what should we be thinking about there?
We haven't really shared the details of what the post-marketing requirement would be. But we've talked in broad strokes, and I think that this is still true. And again, since we don't have the final answer from FDA, I can't speak explicitly to what the post-marketing requirement is. But what has been discussed has been, you're right, sort of longer-term follow-up of patients who receive the vessel after we're approved just to continue to gather more data because this is a first-in-class product.
Okay. That makes sense. Okay, so in other news, last couple of weeks you've had a lot of data presentations, publications. So for the ATEV, both in trauma and in dialysis access. So can you just kind of run through the highlights there?
Yeah. So in trauma, it's actually been a very exciting couple of weeks for us. So about two weeks ago during the VEITH meeting, which is a large vascular surgical meeting in New York, and we had KOL dinners, and we presented some data at that time. We were also fortunate enough to have our sort of landmark paper in trauma describing the results of our treatment of both civilians and Ukraine war fighters who had vascular injuries who received our vessel. That paper was published in JAMA Surgery a couple of weeks ago during the VEITH meeting. And for us, this was very exciting. JAMA Surgery is the highest impact surgical journal on the planet. And so it's great to have our technology showcased in that forum.
What those results showed is that when we look at the outcomes of patients who were treated with our vessel compared to historical outcomes, which is patients who were treated with synthetic grafts like plastic, like Teflon, for example, when we compare our outcomes to outcomes of patients who were treated with plastic historically, what we saw is that our amputation rate was significantly lower. If you had an injury and you got our vessel, you had about a 1 in 20 chance of amputation. If you got a plastic vessel, you had about a 1 in 4 chance of amputation. And the risk of infection was about 1/9. The risk of loss of patency was about half. These are really impressive numbers. These are not subtle, gee, need to look at it for a while to understand if this is important.
These are clinically important outcomes, which is why I think that the JAMA Surgery took the paper, so we're very excited about that, but in addition, you're right, Ally, about a month ago, a month and a half ago, in late October, we presented top-line results of another phase III trial that we've completed. This is with the same vessel, but in treating dialysis patients, and that was a head-to-head prospective trial where we compared outcomes with our ATEV to what is the gold standard right now in dialysis access, which is the arteriovenous fistula, and in 240 patients, what we saw is that over the first year, usability for dialysis and functional patency of our vessel was significantly better. All comers was significantly better than the gold standard.
But for us, even more exciting is the fact that there are some clinically underserved subgroups in dialysis, such as women and obese patients and diabetics, where our separation between our outcomes and the standard of care was even larger. And in fact, we haven't presented this data yet, but we're collecting two-year follow-up. And the two-year follow-up, particularly in our subgroups, is just very impressive. And so I am really excited about this data set. We have, as I've shared on previous calls, we have a meeting set up with the FDA because we have an RMAT designation in dialysis. So we have a meeting set up with the FDA to discuss this data set early in the first quarter so that we can sort of map a path to what a supplemental BLA would look like.
Excellent. So digging in first on the trauma publication and presentation of VEITH, I think that was the first time we saw longer-term data for the ATEV in trauma. I guess can you walk us through? We've seen 30-day data. Now we have it out, I think, to 12+ months. How did that go over with Docs? And can you help us understand if you saw much of a difference between the 005 and 017 trials in terms of those long-term outcomes?
So I wish I could have a slide of the Kaplan-Meier curves here. I can't. I'm going to have to draw them with my finger. But essentially, what we saw in the longer-term outcomes, and this was true for both the civilian and the military trauma patients, the outcomes were basically the same, is that in the couple of months after injury, there was some loss of patency, and there were a few amputations. I want to say that none of the amputations in either of the trials were due to failure of our conduit. In some cases, a limb is so badly mangled that it's not salvageable, and so it's amputated. But if we look at amputations and loss of patency, there are some losses in the early months. But then after about six or nine months, there's no loss of function. There's no aneurysm.
There's no loss of patency. There's no loss of limb, and so the Kaplan-Meier curves just flatten out, and so that really speaks to the durability of the vessel, which to us at Humacyte is not surprising. I mean, we've already published—we're not talking about peripheral arterial disease here, but we've already published results going out to six years in some phase II studies in PAD where we've used our vessel to bypass injured or diseased vessels in the leg, and these vessels are very stable, mechanically stable going out to six years. In fact, we're about to write a 10-year paper that I'm very excited about, so I believe that our vessel is durable, and I think that's what continued follow-up of our trauma data is going to show.
Excellent, and I know in the publication, I think you meta-analytically combined 005 and 017. Is that the analysis that FDA wanted that you submitted? Because I know they wanted data from both trials, so just trying to gauge what a potential label might look like. I'm just trying to understand, and what FDA kind of if this is what FDA is looking at.
I think, again, I can't speak to exactly what FDA is looking at because I don't know. But what I'll tell you is that what's in the paper is actually exactly what we submitted in the BLA. So we submitted data on the civilian trial and the Ukrainian wartime trial, and then the combined meta-analytically results. And the benchmark, which was the historical data looking at plastic grafts, that was actually done ahead of time. And we submitted that to the agency, gosh, 1.5 years ago in May of 2023. So they've had that benchmark for a very long time.
Yeah, that makes sense. I guess another question kind of related to that historic benchmark. I know there's some ongoing registry trials like PROOVIT. Do you have a plan to kind of compare your data to that? And do Docs view that as a good kind of historic comp?
Gosh, I feel like you've been sitting on my window sill, Ally. Yikes. Yeah. So we actually have performed a structured comparison of our outcomes to outcomes of similar patients, propensity-matched patients in the PROOVIT registry who were treated with vein, actually, which is the gold standard in vascular trauma. So we took our outcomes in civilian and military injuries, and we compared them to PROOVIT. That paper is under review right now, but I can tell you that there are no significant differences in outcomes, which is, again, very exciting for us. So I'll let the paper come out before we talk about that in more detail. But I'm very glad we did that comparison.
Okay. Sit tight until that publication. And maybe just last one on this topic. Can you talk to the pharmacoeconomic work you've done for the ATEV? And what gives you confidence that this will be readily adopted by hospitals for vascular trauma, at least given, I think, most the street is expecting a pricing around $25,000 a pop. So just help us explain how you justify that to hospitals.
Sure. So there's two aspects of it. One is the pharmacoeconomic argument, which is potent on its own. So again, if you look at the complication rates for traumatic injuries that are treated with plastic grafts, again, a lot of these fail. The infection rate is quite high. The amputation rate is very high. And those complications are expensive complications for hospitals and for insurers. If you have to do a major amputation of a limb, that's expensive for the hospital in terms of OR time and increased hospitalization. But it's also incredibly expensive for the insurer because they then have to pay for prosthetics and rehab. And so it's a very losing a limb or having a profound vascular infection from an infected plastic graft. These are expensive outcomes.
And so it's actually a pretty easy math problem, even with our expected price point, that if you cut amputations by a factor of five compared to plastic grafts and other conduits, you at least break even and you probably save money. Aside from that, we're also making really good progress on our NTAP applications. So NTAP is a new technology add-on payment, which is a federal program run by CMS, which can provide hospitals up to 65% of the purchase cost of the product. Those applications are submitted once a year. We submitted in October. And in fact, again, this is in the public domain. There's a public hearing about these different applications on December 11th next week. And so we're going to present our case. But to receive an NTAP payment, you have to be novel, and you have to show important clinical improvement.
And I think we absolutely check both of those boxes. So we don't know, but I'm pretty confident we're going to get an NTAP. And that, I think, will really help to drive adoption.
Excellent. Actually, one last one on trauma. Just walk us through your assumptions on kind of how market adoption will take place. I know you have this data comparing against plastic grafts, but now you're going to have the PROOVIT registry comparison. So is it your thinking that ATEV can displace grafts and eat into vein use or not? Or how is that dynamic going to play out?
Yeah, I mean, it's always hard to predict these things. But again, we also, to your point, we have a budget impact model, which we're also about to submit for publication that sort of breaks things into three buckets. One is synthetic grafts and other types of biological conduits, all of which work pretty poorly. And biological conduits are expensive, and they work poorly. So I think the case there is very strong, and I would expect us to displace most of that over time. With vein, there are some patients who have vein available, and they're reperfused right away within a couple of hours. We don't expect to eat into that market.
But for some patients who have, especially with complex injuries, who have no vein available or who are in the OR several hours after their injury, once you get to four, five, six hours after injury and the limb has had no blood flow, if the trauma surgeon has to spend another hour trying to dig vein out of the patient, the chances of complications like amputation and reperfusion injury just go way up. So I believe we will take some of the vein market, particularly in patients who are a long time between injury and repair. If you add up those segments, we've estimated that at complete market penetration, it would be 40%-45% of the market.
Okay. Great. So we have a little time for dialysis. So I think you touched on kind of the subset of patients where you saw particularly good efficacy, and you're running another phase III trial in female patients. Can you just walk us through the rationale for that trial? When should we expect? Is there interim data? And just is that data from that trial needed, or is it gating to filing for an approval?
We don't know if it will be gated or needed. I hope and anticipate that it will not be gating or needed. But that's one of the reasons we're having the meeting with the FDA early in the first quarter. But we decided to set up this trial about a year and a half ago for a couple of reasons. One was even before we had the top-line data on the current phase III trial, which was positive. We knew that we had under-enrolled women. It was partly by how we designed the trial. But women were like 28% of the total patients. And we expected, just based on the fact that we know that fistulas do not mature very well in women.
If you look at all of the women on dialysis in the United States, only about half of them use a fistula, whereas about 70% or 75% of men use a fistula. That's because we know fistulas don't mature in women, and so we expected that we would have a particular advantage in women versus fistula, and then we saw that our trial under-enrolled women, so in part to get our numbers up and also to help us with the pharmacoeconomic arguments, we decided to open up this smaller trial, which is only aiming to enroll 150 patients total, and we're actually hoping to wrap up enrollment of that trial maybe in the first half of next year, and then it's a one-year follow-up, but at a minimum, this will provide outstanding, more highly powered data and more economic data around the advantages of our vessel in women.
Excellent. I guess one question that I get a lot from investors on 007 just has to do with the number of access interventions required to maintain ATEV patency. Can you just talk to that and whether that matters or how much that matters to vascular surgeons and what that actually means in the real world?
Yeah. So when we compared our vessel to fistulas, our vessels did have a higher rate of thrombosis and percutaneous interventions, as you said, to maintain patency compared to fistula. These interventions tend to be outpatient interventions. They tend to be quick. They're done with a catheter, and they're pretty routine in the care of dialysis patients. What I think matters much more to nephrologists and to surgeons and to patients is if the vessel keeps working. And again, particularly in these subgroups, and we haven't shared some of this longer-term data, but I can say here that in these subgroups, like the obese patients and women, the durability of patency between our vessel and fistula, even with these interventions, the differences are striking. So the benefits that accrue to the patient by not losing their access, not having to go back on catheter, that's a big deal.
So it's not a completely free lunch, but I think if you look in the big picture, I don't think this is going to be an important problem for nephrologists. And the important safety issues like rupture and steal syndrome, all of that was equivalent or less than fistula. So the important stuff that surgeons really worry about were not issues for us.
Okay. And with that, I think we are right up on time. So Laura, thanks so much for stopping by. It was great to talk through the story.
Yeah. Thanks so much.