InspireMD, Inc. ($NSPR)

[ Richard Shima, ] Bank of America. Really excited to introduce InspireMD. We'll have Chief Communication Officer, Shane Gleason coming to give a presentation. Thank you.

Thank you. All right. Well, good afternoon, and thanks for having me. There's been a tremendous amount of development in the neuro space in recent years. There have been a number of companies on this stage and ones like it talking about the treatment of stroke, thrombectomy for the treatment of large vessel occlusion in the acute stroke setting. There's now a growing number of companies that are focused on recovery from stroke. We all know that stroke is not just one of the leading causes of death, but also of disability in the U.S. and around the world. But until recently, there has been less focus, less development on the prevention of stroke, specifically prevention of stroke caused by carotid artery disease. Now if you've ever felt your pulse in your neck, you've been feeling your pulse in your -- in one of your carotid arteries. So 2 carotid arteries, one on either side of your neck are -- they form the primary source of blood supply to the brain. And like blood vessels elsewhere in the body, atherosclerotic disease can build up. But the way it manifests, what we're concerned about in carotid disease is actually different than what we're concerned about elsewhere in the body, where we're talking about coronary disease, peripheral vascular disease, we tend to be concerned about occlusive disease, where there's not enough blood flow getting through to supply the end organ or muscle. Here, we're worried about something completely different, where the greatest concern with carotid disease is that it's embolic in nature. And that means that the plaque can break off, blow north and cause a stroke, causing one of those large vessel occlusion strokes I mentioned earlier. That's where we come in. So my name is Shane Gleason, I'm the Chief Commercial Officer for InspireMD. And it's my pleasure to represent a very experienced leadership team and organization that exists to develop products and commercialize products for the treatment of carotid disease and the prevention of stroke. Our flagship product is the CGuard stent. This is not the first carotid stent that was approved in the U.S. That honor goes to the ACCULINK stent from the Guidant Corporation 22 years ago. I launched the second approved stent less than a year later for Abbott and then all the other big cardiovascular companies at the time followed on in the following years, Boston Scientific, Medtronic, Johnson & Johnson. And something all these first-generation stents shared in common was that they're all kind of traditional stent designs, single-layer designs. And we'll come back to it later. But if you look at ours on the left side of the screen, you may be able to notice that there's a finely woven mesh on the outside of our stent. And when we think about the purpose of a carotid stent stabilizing plaque, preventing it from breaking off, getting through the stent struts and causing a stroke, that has a significant advantage. So I mentioned over 20 years ago was the approval of the first carotid stent in the U.S. And -- but there's still something different about the carotid market than all the other vascular beds in the human body, where from head to toe, cerebral aneurysms, I could include stroke thrombectomy, coronary disease, aortic disease, peripheral vascular disease. Whenever there are approved products and reimbursement and guidelines to support their use, things tend to move pretty quickly from more invasive open surgery to less invasive endovascular procedures. Again, literally from head to toe, every other -- this is the remaining 2 or 3 inches of artery in the human body that is still surgery first in the U.S., even though products have been out for over 20 years. But that's changing. We can see in 2025, it was about 45% endo. As you'll see on the next slide, if I've shown you this slide 3 years ago, it would have been closer to 30% endo and still 70% surgery. So the winds of change have arrived. They're driving in this direction, and we anticipate that within the next several years, this will be looking like the other markets up to 70% or so endo with room to grow from there. So what gives me this level of confidence? These are actual claims, Medicare, Medicaid claims, and it's a little small on the screen here, but the gray line is surgical procedures. And the green line is stent-based procedures. There are 2 ways to deliver a stent. We use the acronym CAS for carotid artery stenting and TCAR for transcarotid stenting. I'll talk about that a little bit, but you can see those 3 arrows when coverage expanded for TCAR and then coverage expanded for CAS. And then more recently, there was a large NIH trial, 10 years to enroll, published in New England Journal of Medicine that supports the broader use of stenting. And those 3 tailwinds, you can see the effect it's already had on driving surgical volumes towards stent-based volumes. And we predict that those lines will cross this year. And again, a few years from now, it will look like all other vascular interventions, again, with room to grow. And you can see the impact that, that has on the addressable market size, bringing it to that next billion dollar market that we were all talking about 20 years ago when we first got into this. But that's still only really the tip of the iceberg. Because the majority of that just is focused on the patients that are getting an intervention today. And there are far more addressable patients out there. With 160,000 or so surgical plus stent-based procedures in the U.S. currently, last year, there are over 1 million diagnosed patients that are untreated, patients with high-grade treatable carotid disease that are not currently being treated. Again, back to the guidelines and the evidence and the importance of that CREST-2 study that I mentioned that randomized optimal medical therapy against optimal medical therapy plus stenting for those asymptomatic patients and stenting was shown to be statistically -- significantly statistically superior, tongue twister, than drugs alone. So that should continue to drive more of those diagnosed patients who until recently, they're only -- the only thing they could receive was surgery. Now stenting is available and now there's more evidence that stenting those patients will give them better outcomes. So we see a lot of room for this to continue to grow beyond just the fixed number of patients that are being treated today. So I'm actually going to go forward a slide here. When we look at our strategy at InspireMD, there are really 3 pillars to it. I mentioned that there are 2 different ways to deliver a carotid stent. The first one we call CAS, a traditional stent-based procedure and threaded through a catheter either from the femoral artery or the wrist, the radial artery. Transcarotid, TCAR is a procedure that was popularized by a company called Silk Road later acquired by Boston Scientific. But that's kind of a hybrid procedure where rather than navigating a stent from the periphery someplace, they make a surgical incision at the base of the neck and then insert a stent from there. So it takes a lot of the manipulation out that's required and also the neuroprotection that it provides is very effective. So on that last chart where I showed the climbing number of stents, you can think of those as being split evenly 50-50 between CAS and TCAR. So we have approaches for both of those. And then finally, getting back to the beginning of stroke prevention, well, as more strokes are being treated, as more companies are focused on bringing thrombectomy tools for those large vessel occlusions, One of the greatest -- one of the leading causes of those large vessel occlusion strokes is the carotid artery. So as neuro interventionalists are intervening on an active stroke, they're frequently encountering carotid disease that they need to figure out what to do with on the spot. And the neuro community has embraced our stent design as something that is beneficial for patients in that setting as well. So I've talked a little bit about our stent. A picture says a thousand words. There are multiple pictures on the screen. So I'll try to keep up with it. If you look on the left, those are the 5 first-generation stents that were all approved before the year 2010 that are all still available in the market today. And as you can see, they all have varying stent strut designs, but the red circle there shows the size of a piece of debris that could fit through there. And on the right, you have an even [ magnified ] up version of our stent. And you can see a similar open cell design, but the finely woven mesh on the outside that just makes the pore size considerably smaller. I've used the comparison of -- it's like -- it's almost the difference between a chain length fence and a screen door of keeping flies in or out. So remembering that the job is to stabilize plaque and prevent it from squeezing through the stent struts and breaking off that has obvious advantages. Down below, those are OCT images, optical coherence images, looking through the lumen of the vessel. And if you can see there's kind of a dimple. These are actual human patients imaging, but you can see the kind of dimpling around the stent struts on the left, where you can see that plaque wanting to protrude. And on the right, you can see a much smoother lumen because we have that mesh stabilizing the plaque. So it seems intuitive. You show this to an operator that does these procedures and they get it. It just should do a better job of stabilizing plaque. One of the great things is that we have a lot of clinical evidence that proves that it does a better job of stabilizing plaque. So we have a 3-trial clinical program in the United States. First one is the C-Guardians trial, 316-patient trial, 1-year follow-up has been published and has led to the first approval in the U.S. for this, where I'll show the data shortly, but the best-in-class outcomes. We have then parlayed that to do C-Guardians II, which is that same stent being used in the TCAR approach with the existing company's neuroprotection system. And then C-Guardians III, which we're initiating now, C-Guardians II has completed enrollment and has been filed for approval. C-Guardians III is our stent with our own flow reversal kit for the TCAR procedure. So we can capture all the devices used in that procedure, and that's being initiated now. So I mentioned best-in-class data. That's not hyperbole. These are all of the indication trials that have led to approvals for carotid stents in the United States. The only ones not listed are the ones that have since been superseded by a newer trial on that same device. So this is kind of everyone's best work. And in these trials, the trial design is nearly identical in all of them. Similar patient cohorts, symptomatic asymptomatic patients of the same degrees of stenosis, primary clinical endpoint of 30 days safety, death, stroke and heart attack. And then for efficacy, we go out to 1 year and we add in strokes on the same side, ipsilateral stroke. And as you can see, lower numbers are better here. You'd obviously prefer to have fewer deaths, strokes and heart attacks. And of all the indication trials for any carotid stents that has been approved in the U.S., we had the best 30-day and 1-year results. And in some of the fine print you see at the bottom here, it shows that this is also highly consistent with all of our previously published evidence. One of the nice things about this is that the technology has been available outside of the United States for roughly 10 years. We have over 70,000 patients treated outside of the U.S. and over 1,000 of those in the published peer-reviewed literature. And again, that around 1% 30-day event rate, around 2% 1-year event rate is consistent with everything we have published in the literature as well. So this isn't just we lucked out on a pivotal trial and outside of the U.S. with all the other evidence is highly consistent. So best-in-class data. This is from the CREST-2 trial. Ours was the only stent. It was intended to use all approved carotid stents and they made an exception. And for the last year or so of the trial, they also included CGuard before it was approved because they thought it bettered the chances of stenting doing well. So ours is the only noncommercially approved stent that was included and about 1/4 of the patients enrolled in the last year received our stent. But what you can see are the lines were through 4 years, meds alone, 6% stroke, stenting plus meds, 2.8%, so highly statistically significant. And we zoom in on the front end there, and that's to show that very few events, there were 8 events in the perioperative period. None of them happened on the table. None of them happened on day zero. They all happened in that acute phase after the stent has been implanted and something happened, something broke off. So this procedure can now be done very safely, but the stent that you leave behind matters. And that is really looked at by a lot -- by a number of people as evidence of why having our technology is important. So I mentioned TCAR. We recently had presented the first look at our TCAR data. This is the first 36 patients of a 50-patient trial, which we submitted to FDA of our stent with the existing neuroprotection system in the TCAR setting. And as the physician, Dr. Patrick Muck is the Chief of Vascular Surgery at Good Samaritan Hospital in Cincinnati, when he presented it on kind of the money slide, he said, a bunch of zeros because it was zero death stroke, MI, stent thrombosis, device-related adverse events and getting kind of a deeper look at it, the complexity of the patients that were treated and the acute outcomes were where the real story was. So again, a bunch of zeros on the stuff you want to avoid, but even as you go down a layer, even more compelling evidence. So this is just an illustration of what that procedure looks like where, as I said, an incision is made at the base of the neck. Stent is deployed from a very close distance. And by the way they perform it, they reverse the flow away from the brain during the procedure. So if anything gets knocked off during the procedure, it's externalized, filtered out, blood is returned to the patient. So they don't have the risks of injury during the procedure. But then, of course, when they're done with the procedure, blood flow is reestablished in its natural direction, the stent you leave behind matters. How you put it in there is no longer having any impact and it's the implant that you leave behind that is the only thing protecting your patient's brain. So final slide here. We are publicly traded, available on NASDAQ under NSPR, and we've been fortunate to have a really strong group of investors that have supported us over the last 3 years or so. Three years ago, we announced a significant financing up to $114 million, including the 4 tranches, 2 of which are yet outstanding tied to time after commercialization and the approval and clearance of our TCAR system. And then at the time of our first FDA approval last summer, we did a $40 million PIPE. So we are building an organization around this. We've begun to commercialize in the United States. And although our device looks like something that would fit nicely into the bag of a larger organization, we're currently the only stand-alone company entirely focused on the treatment of carotid disease. So we're building a market-leading organization to support what we think is a market-leading stent. And we'll continue -- looking forward to continue to working with current and future investors to do so. Thanks very much for the time.