All right. We are live. Welcome to the 2025 Piper Sandler Healthcare Conference. My name is Adam Maeder. I'm one of the MedT ech Analysts here at Piper. Very pleased to introduce the team from InspireMD. With us, we have Marvin Slosman, CEO. We have Mike Lawless, CFO. And we have Shane Gleason, Chief Commercial Officer. Gentlemen, thanks so much for joining us.
Thank you.
Thank you.
Thank you. So, you know, lots to talk about, and probably no better place to start than some recent data in the category, the CREST-2 trial that just read out a couple weeks ago. Arguably the most anticipated trial in the carotid space for some time. The data was favorable for intervention, and specifically TF-CAS, which showed a statistically significant benefit over medical management. So the, I guess the question is, what is the feedback then from your customer base? And it would be interesting to kinda hear you answer the question both through the lens of the interventionalist as well as the vascular surgeon.
Do I do a preamble or you jump in?
Yeah. I'll just do a quick preamble.
Sure.
And then let Shane,
Sure.
Kind of handle what the market's saying. I think this is the next significant catalyst in this quest of transitioning from open surgery repair to an endovascular standard of care. If you go back to October of 2023 when CMS approved the NCD, effectively opening up the entirety of the market, for a stenting-first approach, that was a monumental catalyst toward building that endovascular approach. Fast forward to the fact that we had significantly better data from our FDA trial, subsequent approval of the device in the U.S. about five months ago, and the CREST-2 data just adds more credibility and validity to the fact that intervention seems to be carrying the day and moving this market rapidly toward endovascular first. So with that said, maybe Shane can give you a little bit of the on-the-ground response.
Sure.
Read.
So I think the response has been highly favorable from any group that's gonna put a stent into a carotid artery. Just taking a step back, CREST-2 was not one that was set up for intervention to win. The underlying premise was, yes, we've been allowed to do intervention on asymptomatic patients, but boy, drugs have gotten a whole lot better in the last couple of decades. Let's take another look, and maybe intensive medical management on its own is good enough. So that was the underlying premise. And, if you look at just the design of the trial, it was. I don't know a lot of people that were expecting stenting to outright win, given the setup. So when it did, the feedback's been very favorable.
Answering the question from the two perspectives you asked, from an interventionalist, you know, the NCD let us know that it was okay to do stenting in patients that were previously getting surgery. A higher mix of the patients getting intervention for carotid disease, we're gonna get stents. What CREST-2 says is, boy, maybe the number of patients that are getting treated for their disease, period, that should grow. We already had the slice of the pie growing, and now we have the pie itself growing with this. Interventionalists clear win that we can and should stent more of these patients. From, say, a surgical interventionalist, their takeaway is, I'll use the words of one presenter from earlier in the day, someone who is a big TCAR advocate and has published a lot out of the VQI.
His response was, well, the VQI has shown us that TCAR is very similar to endarterectomy in results, less morbidity, less invasive, but in terms of durability, similar. So if endarterectomy looks good, we'll take it as a positive for TCAR. And certainly, if stenting looks good, everything we've seen in the VQI is that TCAR is at least as good as CAS, so we'll take that as a positive. So I think the net effect of this where endarterectomy was numerically favorable to drugs but not statistically so, and stenting was statistically significant, pretty strongly so, p-value of less than 0.02, the takeaway for the surgical interventionalist is it's gonna accelerate my move to TCAR even faster and away from endarterectomy.
Yeah. So I guess just to kinda put a bow around that, that's really helpful color, Shane. You think CREST-2 is going to accelerate the shift to endovascular from open.
Yep.
Endovascular being anything that involves a stent, whether that's TCAR or.
Yep.
Transfemoral CAS.
Yeah. And it really should bring more patients in because CREST-2 included patients 70% asymptomatic, lesions and greater. A lot of those patients are the ones that are medically managed today until their disease progresses. And another finding that we saw from CREST-2 is not only did the patients that got intervention upfront have fewer strokes, but in the course of four years, 20% of the patients who were randomized to medical therapy ended up getting intervened upon anyways. So if the takeaway is the patients who got intervention upfront did better, and oh, by the way, the ones that we deferred, fully 20% of them crossed over within four years anyways, it's gonna lead to more earlier treatment, more, more patients being treated earlier in their disease state, which will bring more patients into treatment, period.
Yep. And maybe just let's double-click on that because I'm looking at my notes here, and I think two-thirds of diagnosed patients in the United States with carotid artery disease are treated with medical management alone. Do I have those figures correct? And I guess how quickly do you think we kind of start to eat into the drug part of the pie?
Yeah. I think, you know, I say this a lot, all politics is local, and it's gonna depend on in any given institution where the patients are going. But if it's someone under the care of, I've talked to a lot of surgeons, a lot of interventionalists who, you know, some of the patients getting randomized in CREST-2 are the ones that they would normally wait on treating. And now this will encourage them to treat more of those patients.
Yeah. I would just add it. It goes back to what one of our interventionalists always says, which is the one-and-done approach to being able to address this disease without the residual of drugs and compliance and those kinds of things becomes much more meaningful because the data supports that story. So we know that patients aren't very compliant with medication to begin with. And I think having an intervention to solve a problem. Remember, we're trying to prevent strokes. We're not stenting patients after the stroke occurs. So I think you'll see more of a conversation that will lead to, let's just solve this issue now. Let's get you a stent and move forward.
Yep.
Okay. Great. That's good stuff. You know, I guess another question would be the transfemoral stents, the stents themselves that were used in CREST-2 are, you know, older generation technology. You've been in the category for a long time, Shane. I think a lot of them were introduced like 2005, 2010.
Yep.
So, you know, old. You have technology that's more, you know, novel and differentiated. There's a couple other stents as well that have recently got FDA approval that are more, you know, novel also. But maybe just compare and contrast kind of what we saw, with the stenting arm in CREST-2 and kinda how that maybe stacks up to some of the data that you've published. Do you wanna grab that?
Yeah. So in CREST-2, it was allowed there. The operators were allowed to use any approved carotid stent system. And then within the last year or two of enrollment, a year and a half of enrollment, they introduced the option of using CGuard, which is the name of our stent. It was the only non-approved second-generation stent that was included. And clearly, there's a reason for that. Those that were running the trial on the stenting arm obviously wanted to optimize the results. They were encouraging sites from the beginning to use closed-cell stents versus open-cell stents because there's evidence that the better scaffolding you have, the better your results will be in terms of preventing embolic stroke or ischemic stroke. So they were already encouraging the use of closed-cell stents.
At the end, they included us, about 4% of the patients, in the stent arm ended up getting a CGuard, which is really about 25% of the patients that were included over that period. We had a little bit of a contribution to the results, but it's well established. There's a really good meta-analysis out there that includes over 100 papers, over 68,000 patients that shows a clear benefit of closed-cell versus open-cell stents and then of second-generation stents carried by CGuard, over either of those.
I think I would only add to that, Adam, that what we need to do now and the goal for the company is to sort of disband this class effect of CAS and TCAR. At the end of the day, these are implants which go into the mix, and we have the best implant. So if we can begin to resolve this class effect, we can be more specific about how our implant performs. A lot of people have said, well, wonder how CREST would read out if all of the patients were done with CGuard. I think you.
Yep.
Mentioned that in your note, which I think is the right question now to be asking so that we're much more specific about the unique advantages to a protected mesh-covered stent.
Yeah. And at risk of getting too specific on the data, comparing C-GUARDIANS, our pivotal trial, to what we saw in CREST-2, the acute results, which just included death and stroke, did not include MI in CREST-2, was 1.3%, which is a great number, comparing to a 0.95% that we had in C-GUARDIANS. With the additions that all the patients in CREST-2 were asymptomatic, a quarter of our patients were symptomatic. Our lesions started at a 80% severity. In CREST-2, we included 70%, and we allowed roughly double the lesion length that was allowed in CREST. So even though in C-GUARDIANS we treated a quarter of the patients were symptomatic, we treated tougher lesions, more advanced disease, our numbers were still lower than what we saw in CREST-2.
Perfect. Really good color there, guys. Thank you. You know, I guess another question that I have coming, you know, out of the data is referral pathway. And how does the data potentially influence referral pathway? I think, you know, we talked about this earlier. Vascular surgeons are doing CEA and TCAR. Interventionalists are doing, you know, stenting. But just any initial thoughts on kind of referral pathway changes?
Yeah. I'll grab it first and then. I think the vascular surgeons that are accustomed to doing TCAR will do more TCAR. The vascular surgeons that are still doing endarterectomy, I think, will begin to think more about TCAR as an option. So it will lead that community to more stenting. For the interventional community, I think this is the biggest lift.
You know, there are those who are passionate about stenting, like the Chris Metzger of the world and the people that have participated with us. They will continue to do more. But there will be a group of interventionalists who either haven't previously done it or did it on a limited basis a while ago that this will reinvigorate the fact that their patient referrals will now land on them as opposed to this being an exception. And really, the CMS decision in terms of reimbursement will help this a lot because it's not just exception on a high-risk basis to surgery. These interventionalists that are seeing patients earlier will now have the ability to treat the patient. So I think that it'll be a lift overall to more stenting in general.
Yeah. And I'll just say very pragmatically, for a company our size, there were roughly 60,000 stents put into carotid arteries last year. There were a little over 4,000 physicians with claims doing that. So you do the math, it's about 15 per. We don't think that the growth of this market will be by doubling the number of operators doing the same number of cases. It's gonna be taking people that are doing cases and them able to treat more patients. A higher percentage of the patients they're treating will get stents, and more patients will be, will come through their service, because of CREST-2. So again, our what we've had, competitors that have come before us, who had a really heavy training lift, who had to go out and train operators on a procedure.
There's 4,000+ doctors in the US that are doing these procedures. We don't need to train 4,000 more. We just need to get our hooks into the ones that are doing it and bring them a next-generation-proven implant.
Okay. Perfect. We're about halfway through our allotted time, and I think it's probably a good point to pivot to the commercial launch in the United States, so you know, a big-picture question to get us started. Just help us understand, help the audience understand where we are in the commercial launch phase. Are you able to share number of accounts that you're selling into? How many are in the VAC process as we kinda think about leading indicators?
So we got approved the last week of June. So just as we entered Q3 was the first quarter of launch. We started then. We had about a dozen reps in the field who we'd brought on board, trained, and were kinda crouched and ready to go at the starting line when we got approval so they could immediately start engaging with hospitals for approvals. We've roughly doubled the size of the organization since then. The numbers we've used are, we're in the neighborhood of 30 people in the commercial organization, most of them in rep roles. And we also mentioned in our Q3 earnings call that we had treated over 100 patients in our commercial launch at this point or at that point. And happy to say that trend has continued well. We haven't disclosed new numbers since then.
But, we're really looking at two things. One is convincing physicians to be interested in our device is not the hardest part of my team's job. That it's an intuitive device. It makes sense to them, and we have best-in-class data. So it's really about motivating them to bring it into their systems. And, you know, probably the majority of the people in this room have heard VAC or product committee, value analysis committee as the real rate-limiting steps. They tend to be measured in, you know, quarters, not weeks or months in terms of how long they take. But, in the first quarter, we did revenue cases and a lot of the really toughest IDNs to get into in the U.S. That's continuing. We're looking forward to moving from evaluation approval into full approval and getting product on the shelf.
But the, you know, the trends from what we said at our earnings call about a month ago are continuing in the right direction for sure.
Yeah. I think the other part, Adam, is we wanna make sure we do this in a controlled manner.
Mm-hmm.
I mean, this is the first time that these physicians have used our device. Most are very comfortable with the procedure itself, but everything that's new, you know, has a learning curve associated with it. We wanna make sure that those experiences are sticky and that this remains their go-to product. So it would be very easy for us to get ahead of our skis at this point. We wanna make sure that we're, you know, landing the right physicians at the right time and getting placed in these hospitals, as Shane said.
Yeah. And I think in terms of the team we're building itself, carotid intervention is one of those procedures where the rep in the room still matters to the outcome. They're not just opening boxes. They're really consultative. So a lot of really good reps in this field like this procedure and are excited about the opportunity to have a next-gen implant and to work for a new dynamic company like this. So we've really been successful hiring a really high-quality team, not just that are good in the room but have experience introducing new products and navigating value analysis committees and product introductions. So it's been a lot of fun to build the team 'cause there's a lot of good people that are interested in fighting for the same cause we are.
Sure. Good color. And on the Q3 earnings call, you did actually provide guidance for Q4, global revenue guidance of $2.5-3 million. Maybe just kinda walk us through some of the key assumptions in that range and, you know, sorry for the myopic follow-on question here, but just, you know, help us kind of understand kind of how the business trended across Q3 and kind of help you arrive at that Q4 outlook.
Yeah. The underpinnings of the guidance was really twofold. One was the fact that we were coming off a record quarter internationally, so we had to be mindful of the fact that we did $2.5 million in the third quarter, so we wanted to be mindful of performance that could translate and carry over into the fourth quarter for international. And then we were really still on the very, very early stages domestically in the U.S. with the commercial launch that they've been describing. So, you know, and taking into account what Marvin was saying, you know, we were trying to do this in a very controlled manner. And so we wanted to kind of, you know, build that into the overall structure of the guidance.
Net net of it all was we thought we could at least show some sequential growth in Q4. And that's sort of how we get to the $2.5-3.0 million. Excuse me. At this point, I think two-thirds of the way through the quarter, we would say we expect to be at the higher end of the range. You know, we, you know, we're very pleased with how we performed so far.
Okay. Fantastic.
For those that don't have the numbers in front of you, we did $2.5 million in Q3. It was $2 million internationally where we've been, you know, established for quite some time. That was a record quarter. We did $500,000 in the US. So the basis was if we can match that record quarter internationally and then grow in the US while we're still in a controlled launch phase.
Yep. Good color there. And, you know, I guess, just to circle back, number of accounts, have you disclosed that previously? I can't recall.
We have not.
Have not. Okay. Maybe we can transition to the pipeline. You know, two kinda big pipeline products from the hopper. The first one is integrating the CGuard stent into Boston or Silk's EnRoute neuroprotection device. You have a trial that's supporting that submission, the C-GUARDIANS II trial. What's the latest on that study and how are we thinking about potential FDA timing for that product? And then we'll tackle SwitchGuard separately.
Yeah. So the timing remains the same, first half of 2026, which is, I think, what we had indicated before. Enrollment progresses very, very nicely. You know, again, as a reminder, the most important factor in these trials is that we're very careful about the selection of patients and that the procedures performed go according to plan.
Thus far, we've got a lot of enthusiasm from the vascular surgery community, and the enrollment is going very well. We're still calling first half of 2026 for that approval submission to FDA in spite of some of the headwinds that FDA has had. We're in good contact with them. We plan to initiate our C-GUARDIANS III study, our SwitchGuard, project in, right after the first quarter of 2026 to enroll in that trial. Right now, we're calling first half of 2027 to have that neuroprotection system 510(k) cleared. Everything is going according to plan technically and otherwise. Obviously, enrollment is the longest pole in the tent there related to getting patients enrolled in the trial. Just as a reminder, it's an N of 50 for C-GUARDIANS II. 50 patients for that study. It's 110?
Well, so that's like 104, 105, somewhere in there.
104.
Just over 100.
For the SwitchGuard trial, for the 510(k).
And we'll have twice as many sites, more than twice as many sites in C-GUARDIANS III that we do in C-GUARDIANS II.
The encouraging part, Adam, is that there is so much enthusiasm on the part of the vascular surgeons to use our device. So this has not been an issue of trying to convince people to enroll in a trial to know where this follows the same path of our original C-GUARDIANS I, which is we've got enthusiastic investigators that really wanna use this device and are looking forward to incorporating that into their practice. And you know the difference, by the way, between people that are just enrolling for the sake of doing it.
Yep. And you know, I guess, really good color there. I think that's the first time I had heard 105 patients for C-GUARDIANS III, which is the SwitchGuard study. Number of sites, it sounds like double.
25.
25.
Yep.
25 for C-GUARDIANS III.
Correct.
and then just the primary endpoint, are you willing to share what that is and duration of primary endpoint?
30 days. So that one will be with, we're using the approved CGuard Prime stent. During the course of the trial enrollment, it will have picked up the TCAR indication specifically. But the real purpose of C-GUARDIANS III is it's the trial to get the 510(k) clearance of the neuroprotection system. You know, rule of thumb, stents that stay in the body, our PMA devices and things that stay external, it's just that 30-day safety endpoint. Death, stroke and MI, very traditional with the other carotid intervention trials.
Yep. Okay. Perfect. And maybe we can talk about feature set of the SwitchGuard system, you know, and how you think it compares, contrast versus EnRoute. You know, I think you've been a little bit stealthy in terms of the device itself. I have seen pictures finally.
Yes.
But would love to kinda understand, you know, the feature set and then how you're thinking about pricing that technology relative to the EnRoute system that Boston has.
So the functionality will remain virtually the same. We felt very, very comfortable with going down the path of not having to retrain vascular surgeons on the technique of reversing flow. There are other companies that are attempting other ideas. We wanted to make sure that was very consistent. It was a very heavy lift for Silk Road at the time to get this therapy developed. So the functionality itself remains virtually the same. The feature set, we haven't really talked openly about, and we'd prefer not to until that becomes real. Let's just say that we wanna take full advantage of a second mover advantage.
You know, we've got certain features that we've built into the new technology that physicians have been asking for a while. And we believe they're not just convenient but significant to make the procedure safer and easier to perform. Again, remembering that SwitchGuard is a neuroprotection system. It is just a way to protect the brain. And so we're trying to make that as advantageous as possible for people to select our device. As far as pricing is concerned, we haven't really talked openly about that. But as is the case with our current stent system, we're going to, you know, continue to stay in a bandwidth that people are accustomed to while at the same time trying to get a premium for those features.
Good color. About a minute left. Might try and sneak in one or two more here. You know, I guess,
we'll answer quickly.
Yeah. Sorry.
Speed round.
You know, I guess we'll stick with the pipeline. Tandem lesions, which, you know, might be a little bit unfamiliar for some folks. You have an early feasibility study there. I think on the Q3 call, you said you're over 50% enrolled.
Mm-hmm.
Maybe just talk about exactly, you know, what, what this procedure is, what you're kinda solving for. And, you know, on, I think on the one hand, it potentially grows the, the TAM. But I think on the other hand, it also kind of, you know, helps drive access with neurointerventionalists. And so it's kind of a double whammy. But would, would love some thoughts there.
Yeah. Let me get started. Shane may add some color afterwards. But the whole intention of this was to demonstrate to the neuro community in particular the protective value of our mesh, especially in acute strokes, so in about 250 thousand strokes a year, more or less, about 20% of those include the carotid. Therefore, by definition, a tandem lesion, and so what we wanted to do was to demonstrate the value of CGuard and that protective capability in those acute settings, which is the reason we set it up as an early feasibility study with Adnan Siddiqui at the Jacobs Institute. The priority there was to educate and provide access to this technology to the neuro community. Whether or not getting a label for this is the endgame or not is still to be determined.
But so far, I think there's been a huge receptivity to this idea that when they're stenting in this acute environment, with thrombectomy, by the way, so the carotid superhighway has gotten awfully busy with thrombectomy devices, that this should be the go-to device for all of the reasons that we've, you know, discussed. You may wanna add.
Yeah. With the explosion of stroke thrombectomy treatment, acute treatment for stroke, the reason we stent carotids is to prevent ischemic stroke. It's one of the leading causes of ischemic stroke. So frequently, when neurointerventionalists go in acutely for a stroke, they encounter carotid disease on the way in. So using our stent as a way to stabilize it, either on the way in or the way out, is kind a cutting edge for stroke treatment. And so the early feasibility study is a way to be on kind of the leading edge of that.
Let me just make a quick mention 'cause I think it's important to wrap on this one. Measuring success in that setting is a very different game, which is why we've sorta hesitated as to where we wanna go to this next, right? By definition, these patients are having a stroke, right? So it's not the same measure of success, and so that, you know, sort of leads us to this cautionary. Are we redefining success in an environment that is, you know, very challenging to begin with? So that'll be part of our assessment as to how far we wanna take it, whether we wanna go to a full label or whether the neuro community just gets more and more comfortable with using our stent.
Perfect, well, we're out of time here, but wanna say thanks again, Marvin, Shane, and Mike for joining us.
Thank you.
Thank you.