Good afternoon. I'm Josh Jennings from the TD Cowen Medical Devices research team. We are excited to have the CEO of Anteris, Wayne Paterson, here in Boston live, for a fireside chat. Wayne, great to see you in person. Thank you for making the trip and participating in our conference.
Yeah, great to see you. Thanks for having me, Josh.
It's been a big start to the year for the company, for your team, after a big 2025. You know, I think the we've been learning more and more about the DurAVR platform and maybe to start for those investors who haven't gone as deep, we can just talk about the platform, how it... its disruptive potential and this concept of a biomimetic valve and restoring the aortic valve back to closer to its native state and allowing for healthy laminar flow.
Yeah. Thanks, Josh. It's quite a long story. It goes back about eight years. I won't take eight hours to tell the story, but we took, I think, a very, very different approach. You know, I have a different background. I'm not from the med tech industry, I'm from pharma when I took this. It forces you to look at the space from a disease management perspective as opposed to an engineering project. I think the physicians have told us that's one of the things that was very different. We had a blank piece of paper, my colleagues and I, and we're looking at spaces in med tech as to where we could use an existing technology we had, which was a tissue platform called ADAPT, which you know well, Josh.
Very good tissue, 50,000 patients, clearly not in the TAVR space. A very limited space by revenue, surgical repair, and not a great investment thesis, and we were publicly listed. I was chairman of the company at the time. We pulled in a bunch of physicians from the biggest centers in the U.S., very important KOLs who were chosen for their volume, their podium presence, their publications, and all that stuff. Very deliberately, about eight years ago, and basically said to them, "If you had a TAVR device, what does that look like, if you had a new one?" That's two products that are existing were there then. They said, "Look clinically better and balloon expandable." We learned a lot that day. One, that the delivery system mattered.
It was a barrier to adoption, because, you know, a balloon is obviously easier to use. 90% of what an IC does is balloon-based, which means the self-expanding is a bit of an outlier. Two, clinically better meant compared to the standard of care. What struck me at the time was that the TAVR space was starting to move. The products that were in the market were fantastic. They were developed for one setting only, which is a high-risk patient who probably mid-80s, who had no pharmacotherapy obviously, and they were too sick for a thoracotomy, so they had no options, and they were able to get that valve into that patient. They lived about three years. So you didn't see any of the downside. The valve didn't have to be amazing. Patient lived.
From 2019 to 2021, the mean age of the patient group dropped from 85 to 73. Suddenly the patient group got younger. The products did not change. We looked into the space, and said, "Okay, physicians are asking us for clinically better." What they meant was a pre-disease mean gradient, which is how they measure the disease. 5- 10 mm of mercury couldn't get that with existing products. We also tried with the existing valve designs, which everyone used called bioprosthetic, and we couldn't get that valve to mechanically do what it needed to do to get the mean gradients down. We had to create a brand new class of valve, the first new one in 20 to 25 years called a biomimetic. It's much more physiologically and anatomically correct, and lo and behold, it behaves the same way.
That was the starting investment thesis. There were go, no-go gating items. For us creating that investment thesis, we knew we had to be better or there's no point moving forward. From patient one to what is now patient 140, we have consistently achieved those mean gradients of 5-10 mm of mercury. On the back of that, we have got things like laminar flow that is unique to DurAVR. We're remodeling the left ventricle, which is a precursor to heart failure, which AS patients die from even after a TAVR. There's a lot of nuances with this product that have come about.
It has obviously a very big profile clinically, as you know, Josh, and also in the valve-in-valve setting, which is a wild card that kind of came out of nowhere as these valves started to fail. Patients getting DurAVR in the valve-in-valve are actually getting better mean gradients than when they got their first valve, which is clearly unheard of. We pretty much at this point established what we set out to do. We passed the gating items or the hurdles to maintain an investment thesis, which is to be clinically better and as easy to use as the market leader. We have a lot of support, as you know, Josh, from the highest name clinicians in the space.
No, absolutely. It's an impressive lineup of your clinical or scientific board and ton of key opinion leaders that we see often on the podiums at these major interventional cardiology meetings. Thank you for that download. Just to follow up, you know, there's some positive clinical signals that are in play from those 140 patients that you referenced. You have the first in human, I believe the Embark patient cohort and the early feasibility study patients that combined get you that 140. I think the first 100 where there's a big presentation at London Valves.
Right
... last November.
Yep.
Maybe just to reiterate some of what you already put on the table with some more detail just about what you're seeing. You talked about gradients, you talked about effective orifice area. Maybe build a little bit more on the laminar flow, how that's determined, and also this concept of LV remodeling.
Yeah. Thanks. I think there's a couple of things where by virtue of the radical design change that we brought about, there were things that we weren't necessarily fully understanding or targeting that we found out a little later on. Some of our clinicians, of course, identified things like laminar flow and LV remodeling. If you think about the TAVR discussion 10 years ago, it's a very, as you know, covering the space, it's a very different discussion to the TAVR discussion today. We like to say this is not your father's TAVR because people no longer just talk about mean gradients or EOAs. That's a mechanical engineering view on the product, but it's not a view on total disease management.
It's not a view on the clinical outcomes per se, of what affects a patient with aortic stenosis, whether it's the ventricle or the aorta, not just the valve opening and closing. We did a 140 patient CFS. That's a very big number because we wanted to also de-risk the pivotal study. We could have done 25-50, but we chose to do a lot more in patients that would otherwise be excluded from trials because their comorbidities would make them excludable. Very, very sick patients is what I'm saying. What did we find out? Firstly, our longest cohort is pushing up past four years. Right? Our cohorts, there is nine of them stretched from four years to very recent.
Patients who had mean gradients of 100, and I've been in the room with that particular patient. You know, that's a very sick individual. Tricuspid, bicuspid, we've got valve-in-valve, tortuous anatomies. We've got one patient who has a DurAVR in the aortic and the mitral position, so he has two DurAVRs in him. We've covered everything. We've learned that the biomimetic design, much more aligned physiologically and anatomically, gives you the pre-disease mean gradients. That's done. It also gives you laminar flow. Laminar flow is what you have when you're healthy. A stenotic valve has turbulent flow by definition of how the valve is deformed and not working, it's dysfunctional. We've also learned through studies that when you put in the standard of care, you also have turbulent flow. They don't alleviate the flow side.
That leads to back pressure on the ventricle. The left ventricle gets bigger until the point where you have a dysfunctional ventricle. It can't push, that's heart failure. You have left ventricular hypertrophy, and the current products are exacerbated. They're not improving the turbulence any more than a stenotic valve. It's not the mean gradients the other side. The number one cause of death for AS patients, heart failure. Right? We start to look at total disease management and disease modification. We've seen 30% reduction in the LV mass over six months. That brings that LV back into the realms of normal, which is incredibly huge when it comes to how we're looking at these patients from a mortality perspective. When you think about the fact that the patient population has gotten a lot younger, right?
That 85 to 73 now in the 60s, the products didn't change. The products that were designed to solve for the older patient, mid-80s, high-risk patient, and did a great job of that, are not necessarily designed for your low to intermediate risk, younger, 60-something patient. The requirement of a product for those patients is completely different from a clinical perspective. We're seeing that. We're also seeing outstanding results in small annuli and, you know, 40% of the market is small annuli, female patients and so on. We are significantly superior in that state, as well as valve-in-valve, which you consider to be a small annuli patient because of all the debris that's left inside. We're getting better than first valve mean gradients in that group.
There's a lot going on by virtue of the fact that this design is so radically different.
I think one thing that stood out to me in terms of the London PCR, London Valves presentation was just the patient-prosthesis mismatch rate was so low.
Yeah.
Maybe just help us understand the importance of that and how differentiated, I think it was 3%, which is very low, especially in that small annuli.
Yeah
... patient cohort.
Yeah, you're spot on. PPM, if you ask most interventionalists, is pretty much the bane of their life when it comes to treating. It's the one thing that really is consistently challenging for them, and it really is meaningful. It's not something they can ignore. The PPM on the other balloon-expandable device is about 30%. That's patient-prosthesis mismatch. It's when the patient and the valve size doesn't necessarily match. It leads to poor outcomes, it leads to higher mortality, it leads to poor flow. The PPM rate for our product is 3%. It's an order of magnitude lower, and I wouldn't say it's inconsequential, but at 3%, you know, obviously, it's less of a problem for patients moving forward.
That is, in spite of all the other data we have, which is fantastic, that is a huge benefit clinically for both the physician and the patient. That is, again, is a function of the valve design.
As before we talk about the IDE study PARADIGM, wanted to just check in on 2026 and any presentations or milestones we should be or should have on our radar for this, these early clinical patients, the early feasibility study patients as we get to CRT and New York Valves and TCT later in the year.
Yeah. I think it is a great question. I think, you know, one of the things we're very mindful of is ensuring that there's enough information that's going out there in parallel to our pivotal study, which again, is why we have a large number of ex-pivotal study patients, 140. It's a very big number. The TAVR spread out over many, many years now, four years, and you talked about the 100 patients in one year. You can consider, I guess, basically three buckets of where to look for information and news on Anteris. One is, you know, every major conference coming up, like CRT is the next one. Next weekend, I think you'll be there. We have a podium.
Every New York Valve, London Valve, everything in between, you'll see Anteris data being presented, and it's highly anticipated data and, you know, presented by very credible physicians, obviously, in the TAVR space. That's the first part. We do have all of those presentations. Things like flow will be presented, LV remodeling, like the topics we're talking about are on the podiums this year. The other part to look for, of course, is the normal statutory news flow that we actually have coming out each quarter, of course. Finally, you know, updates to the pivotal study as well. There's three buckets of news flow to look for with Anteris.
Excellent. On just flow data and this reestablishment of normal healthy laminar flow, you know, in this... I think one of the mechanisms for the clinical community to measure that or your investigators is through cardiac MRI. Maybe just give us an update on how prevalent cardiac MRI use is in TAVR patients post-implant, and how will that progress over the coming years, and then we'll dive into the PARADIGM trial.
Look, that's a great question. I think, you know, when we started this with a blank piece of paper, the likes of 2D MRI, 4D MRI were not in use very widely spread. Some of these topics were not even discussed because you didn't have great access routinely to look at it. Fast-forward to particularly the last two or three years, I think 2D MRI, much more widely spread. 4D MRI is certainly getting a lot of prevalence. In our pivotal study, we'll talk about that, it's certainly there. It does give you that ability to really identify the flow. I mean, you really see it, whether it's our product or something else. When we've really seen, you know, great imagery of the flow, it's through those technologies, and they are much more widely spread.
In fact, we have a doctor focus group meeting on that tomorrow morning with leaders in this field, Pankaj Garg, João Cavalcante, and others in that space.
Is there any initiative that you're aware of by Medtronic or Edwards to start using cardiac MRI to evaluate their TAVR patients post-implant for the Evolut and SAPIEN platforms? I don't know if Medtronic's trying to integrate that into their SMART trial follow-up, but I'm not aware. Just wanted to check and see if your team was aware and whether or not that trend could start to move forward. I know there's a limited number of cardiac MRI systems out there, so not every patient can get imaged, but...
That's true. In our study, it's part of the study. I think here's the critical question. One, it's really important information to have. We now know why. I think just a few years back, that wasn't well understood. Is there a massive incentive for other of those companies to be studying this in a trial? Not necessarily from the results we've seen so far. We've looked at this in both Edwards and Medtronic patients, and the flow reversal has not been amazing.
In fact, it's in line with the stenotic valve. Now, I need to see more patients to understand that, but I don't see a huge incentive when you've got a product like DurAVR that has near laminar flow versus products that don't alleviate the flow disruption or turbulent flow between a TAVR and a stenotic valve that hasn't been treated.
Why does it matter? Well, the SMART study showed us a couple of things. One of them was 40% BVD rate in the Edwards arm over 12 months. That's some degree of structural degradation based on flow, all right. We know in recent other studies where we saw failures, flow was a problem. We know that flow is a leading indicator in valve degradation. In fact, it's probably the primary culprit. Lack of laminar flow, turbulent flow is one of the contributors. Structural integrity, another one. Tissue is the third. I don't see a huge incentive, but the technology's definitely become more widely spread.
Excellent. One more topic before moving into the PARADIGM trial. Sorry. Just thinking about all the work that's been done over the past number of years, the pre-IDE study, early feasibility patients and analyses. It's clearly generated some buzz within the clinical community in terms of, and we'll talk about the investigator sites that are building in the United States and internationally. It's also caught the attention of strategics, and you guys had an outstanding capital raise recently with Medtronic investing as well. Anything you can just share around that investment. I think Medtronic, they called out on their last earnings call as part of their kind of venture investment strategy. They was also talking about their M&A strategy.
I mean, is there any strings attached to that investment, or is it, right of first refusal or anything you can comment publicly on that investment by Medtronic?
Yeah. Yeah. I mean, 'cause the documents pretty much reflect publicly what was in that deal structure. I would say a couple of things. All of the strategics talk to us or have spoken to us fairly regularly. That includes all the usual suspects as well as J&J and others. We've been down this path a lot as well Medtronic. As you can well imagine, as the data starts to build, we're all working with the same physicians if they're working at the top tier, which they do. Even, you know, their study chairs and those folks were folks that have been on the DurAVR journey since the blank piece of paper. There's a lot of crossover, obviously. How do I look at it? As an investor, I look at Medtronic as an investor.
We align very closely with their values, their patient centricity, maybe more than other companies in our space, as I see Medtronic from that perspective. They're also a competitor. They have no special rights. We have potentially discussions around co-development, co-promotion, co-manufacturing, and some of those discussions will be ongoing moving forward. You know, we have spent eight years pre-marketing and developing this product from a science point of view. I think from our perspective, we see ourselves as very much experts in TAVR, and we will continue to do that. I think my job as an investor is to make them money, and I will. They are a competitor. My job as a competitor is to take their market share, and I will. That's how we look at them.
No, that's pretty clear in terms of. Thank you for that. One more follow-up question. Just it seems as if that investment by Medtronic takes on more meaning now that we have the Evolut Low Risk six-year outcomes on the tape and the re-intervention rate climbed a touch, and then they had that preliminary seven-year analysis where.
Yeah
... their re-intervention rate reached statistically significant levels higher than the surgical control group. How does that impact your view of the competitive landscape in this TAVR market? Does it enhance the opportunity for Anteris? Seems like Medtronic may be under a little bit of pressure, but, you know, I think there's a lot more learnings for investors in the clinical community in terms of how it's digested and how utilization decisions are made.
Yeah, no, it's again, a great question. Obviously, this is very recent, occurrence, and of course, we know, again, the physicians involved. Look, I look at them from a portfolio point of view across their company, if I was to put that product for them into a BCG matrix, it's probably slipped down a few notches or a few quadrants. I think it does not bode well moving forward. There's speculation around that particular product, maybe around the tissue, and so many things that we don't yet fully know. I think it's gonna be a bumpy ride for them, and it probably made our commercial strategy just a little bit easier on that side. Remember, majority of Evolut is used in the small annuli patients.
As a self-expanding, it is certainly more challenging to use, and the physicians will tell you that versus a balloon expandable platform. The DurAVR product is, you know, exceptional in small annuli, and it's a balloon, so it's easier to use. I think their market share was always at risk. They're obviously product of choice for valve-in-valve as well, which we're obviously, you know, very good at. I think it doesn't bode well for them in a portfolio perspective. Doesn't change my view on when we launch this product, how we'll go to market, and how we'll take market share.
Got it. Well, let's talk about the PARADIGM IDE approval and that design and maybe just the highlights and what was most satisfactory with what your team got through and then got put into that clinical trial design that was approved by the FDA.
This is the bit I love talking about because having come from 20 years in big pharma, therefore being around a lot of trials, this is by far singly the best clinical trial protocol that I've seen. Not me, the team put it together. I've been around +20 phase III studies, right? I've been around a lot of studies. Why is it fantastic? One, it's a very, very small number of patients, relatively speaking. Two, it is a head-to-head. It's the first registration head-to-head for TAVR. That matters, right? Because not only have we got to prove clinical superiority, I guess, to an extent, we've got to show that data in a publication when we go to market. It's not enough to pound our chest and say we're great.
The 2D MRI or the 4D MRI, as it is in that study, this will be the first time that those patients have been captured and as our secondary endpoints, hemodynamic superiority against the other balloon, laminar flow, LV remodeling, all of those things are in this study in a way that's never been captured before. It will be a seminal paper, and every physician hospital wants to get involved in this to have their name on it. It probably will change guidelines. Now, on back of that, it's a global study, so it's U.S., Europe, and we're also getting four labels: low, medium, high risk, and valve-in-valve in the one study under the auspices of the PARADIGM umbrella. Of course, if you look, that's time and place, of course, that's a victory for us.
If you look at the other companies, it took quite a few years to get those labels. We've got the benefit of that work now applying to this study. It's an amazing study. It's covering a lot. It's relatively short to enroll, you know, let's say Q1 next year. We're gonna get a lot of data that I think will shift the way physicians look at treating aortic stenosis because we're now looking at the mortality markers. We're looking at total disease management and disease modification with remodeling of the left ventricle and so forth.
Excellent. Just on that enrollment pace and potentially, completing enrollment in Q1 of next year, I mean, I think you have some precedent just in terms of the experience with the early feasibility trial in 2025 and the pace of enrollment there. Maybe just build on that and help enhance that statement I just made, and then also what you're hearing from investigator sites that gives you kind of gets you to that timeline.
Sure. I think the best comp is actually the SMART study.
Oh, sure. Sure.
SMART study was a similar number of patients. Now we are in and around 1,000 patients, it's randomized. You've got 500 DurAVR, 500 standard care. Anyway, 1,000 patients. Now the SMART study was roughly the same. It was also an interesting study, I think the anticipation around the DurAVR study is actually much, much higher just because of the clinical differentiation. That study took about 12 months to enroll. You can kind of weigh that up. On the back of that, we've investigated meetings at all of the big conferences. I mean, we have been working with our sites, some of them for seven, eight years. You know, we've got people in the field in Europe and the U.S. now who've activated the sites, so they're ready to go.
The enthusiasm to recruit is incredibly high. I think even higher than probably what our ability is to supply product logistically. We've got a timeline. It's built around also our ability to manufacture, which is not bad. I think you could probably recruit it in six months. The physicians tell us that. We can't logistically do that, and you wouldn't want to do that. It's, yeah, it's highly anticipated. We will be on track with the timelines we've put out there, assuming no regulatory delays or anything of that nature.
Excellent. Just a clarification, I think on ClinicalTrials.gov, it cites 1,650 patients who enroll, but I think that includes the valve-in-valve 150.
150 valve-in-valves.
another maybe 450 of continued.
In the low-risk cohort. Yeah
... continued access program.
There is two cohorts. The approval comes after the first group, which is the roughly the 1,000.
Great.
We have an ongoing part after that, part two.
Yep
on the low-risk side.
Perfect. Perfect. Any comments on the early experience within the trial? Just, I mean, I know you can't talk about outcomes, but just in terms of the buzz that's being generated, investigator sites wanting to sign up. Any other details you can share just on, I think the overall just demand to get involved in the trial and investigate DurAVR?
Yeah. As you can imagine, the biggest sites in the world are involved in this study, signed up, validated, qualified, ready to go. You know, it includes the Clevelands, the Columbias, and big centers in Europe who do, in some cases, double the volume of some of the centers here, in Germany particularly. They're all pretty much locked and loaded. We do have patients already in the study. We do have anecdotal feedback from those patients, and we have patients both in our arm and the control arm. We're already getting a sense now.
What I think investors should be aware of is that when we look at the patient data outside of our pivotal, those 140 patients is a much bigger number than was required in an EFS, for the very reason that we wanted to make sure that we knew everything about this product going into the pivotal from a risk point of view. The physicians will tell you within 1%, 2%, 3% you can predict what the outcome on the, you know, the hemodynamic performance and gradients looks like. We know that it's fairly consistent. Investors don't need to wait till the end of the study because we already have a good proxy and we'll continue to see updates on the ex-pivotal study patients. It will enroll very quickly.
Assuming enrollment completes in Q1 of 2027, 12-month follow-up, you get an approval decision potentially sometime in 2028. At that time, you will have some longer term follow-up, as you've already detailed on this discussion, that some of your patients are out to four years already. What will be the kinda average, I guess, follow-up period for this early feasibility study patient group as we get out into that 2028, 2029 timing? It's, I mean, some of it may even be at least five years is my guess.
Yeah, no, it's a great question. I was just trying to do the quick math in my mind because there are nine cohorts.
Right, right.
They all spread out over a period of time. Look, by that point, my longest cohort's gonna be pushing up seven and a half years. They're doing great. We do remain in touch, and I've even spoken personally to some of those patients. I don't really know what the average is across the board.
Sure, sure.
It's gotta be in the four-five range by 2028, for sure.
Sure.
We have good long-term data, good follow-up. Of course, you've got 12-month follow-up on the, on the pivotal study. You know, the primary endpoint is non-inferiority. I mean, we already know what that looks like based on these current patient cohorts. We know what they look like at 12 months from a rehospitalization, all-cause mortality, all stroke. We know we have a good feel for that data, and it's a big enough number that you already know what the outcome of this study will look like from that perspective. Secondary endpoints, we also have a lot of information on that relative to the competitors. I think we've got a lot of data, and we'll have just more and more data as we come out the other side.
Sort of going back to the beginning of the discussion and to talk about the design of DurAVR. I forgot to just ask about the delivery system and the uniqueness of it being within the balloon-expandable delivery camp. Two-part question. One , I mean, do you expect any patent events, litigation by a competitor? Two, maybe just highlight some of the features of that delivery system that are advanced.
Sure. I love that question because when we had a blank sheet of paper, blank canvas, we were also fortunate enough to be able to look at the IP that's out there. Now, the physicians were very clear they wanted balloon expandable. Just easier to use. I do believe if we put this on a self-expanding, we wouldn't be having this discussion. Even though we've got the best valve objectively that's proven, without that delivery system, it's 50% of the equation. Now, what we did do, because there was obviously a balloon expandable platform, but remember, balloons are not unique to TAVR. In fact, a lot of what an IC does is balloon-based. Right? There was a lot of balloon stuff out there, but it was old and it was a different technology.
Once we got into it, I basically put the IP lawyers and the engineers and the physicians all in a room. That way we knew what we were bouncing off, where to maneuver. Remember, we're creating an investment thesis first and foremost, and it's not investable if you don't have IP protection out the other side. That was paramount and core to those first days. On the back of that, we changed technologies. Balloon technologies had actually advanced, and the way our system was set up with physician, as you know this, a lot of physician input, not one and done, but daily, weekly, monthly. These guys were coming to Minneapolis working on animal labs and cadavers and so on. There was a lot of iterations. Things like commissural alignment, which were not available, physicians wanted that.
We pioneered it, I would say, and got it to work, and physicians will tell you it works wonderfully. Our balloon is completely different, the way we crimp the valve onto the balloon and so on. There's a lot of technology differences to the existing platforms. The first remit was that it had to be as easy to use as the current products in the market so that the learning curve was minimized because it is a barrier to adoption. I think we got all of that right. I think it's a better catheter and delivery system. The physicians tell us that who've used a lot of our product and the others. We achieved the things we needed to do. That was part one.
Excellent.
Part two was?
Uh, I was just-
Feel free.
I think you answered a lot of it just with enhanced features and.
Right.
We've covered a lot of ground in this half hour. I think you guys are positioned to cover a lot of ground throughout 2026 and into 2027, so we're looking forward to following and tracking your guys' progress, continued progress I should say. Thanks so much for the time today participating in our conference. Again, great to see you in person.
Yeah. Thanks, Josh. Thanks for having me. Really appreciate it.