Okay. Good afternoon. I'm Josh Jennings from the TD Cowen Medical Devices research team, we are very excited to have executives from Pulse Biosciences participate again this year. I wanna introduce CEO Paul LaViolette to run through a presentation and then open up to Q&A after. Paul, thanks so much for being here and supporting our conference.
Thanks so much, Josh. Appreciate being here and, of course, very appreciative of Cowen, for all you do in the healthcare ecosystem. Looking forward to sharing these thoughts and saving ample time for interaction and Q&A. As Josh said, my name is Paul LaViolette. I'm CEO of Pulse Biosciences. I've been with the company a little over a year now, after a 45-year career in med tech as an operator and investor. I've been exposed to many, many fantastic technologies and markets over the last number of decades. I was particularly enthralled with Pulse Biosciences when I came across this technology several years ago. I immediately joined the board, and after coming to meet Bob Duggan, and then joined in as CEO shortly thereafter.
It's been a tremendously enjoyable and I think productive ride, and I'd like to spend a little bit of time talking about what has been a fantastic 2025. We did a lot of cases. We did a lot of regulatory submissions. We really advanced our story, and in 2026 we're beginning to see the fruits of years of development and the last one or two years of clinical progress, and ultimately now turning in data that is quite spectacular and I think evidence of the foundation that we will create using nanosecond pulsed field ablation.
As we talk about why we're here as a company, we really have a mission to build an extremely strong, vibrant, viable company focused on delivering all of the benefits from this very novel technology of Nanosecond Pulsed Field Ablation into multiple clinical areas of application. We are pursuing this quite rigorously, and as I mentioned, we've done a number of studies. We have IDEs forthcoming which we'll describe. We now are in possession of a flow of data that's starting to really concretely validate the clinical benefits of NSPFA, showing in fact that it has all of the benefits of pulsed field ablation but is indeed a novel energy associated with nanosecond pulse delivery, which we'll describe in more detail. When we think about our team, it's led by technology. We remain a technology and clinically focused stage company.
Jon Skinner is here with me today. He can interact with us as well on Q&A. The third member of our executive team, Darrin Uecker, is our Chief Technology Officer. Years of development in various energy systems, robotic delivery systems, and has built a spectacular technology and clinical organization. We have a wonderful array of Chief Medical Officers, most importantly for this discussion, David Kenigsberg, who as you may know, is a key opinion leader, practicing electrophysiologist, and really a landmark physician in the field in many ways. We have a fantastic Board of Directors and investor group. Bob Duggan, many of you know, is legendary for his entrepreneurial and investor instincts. He's built fantastic value at all of his companies in partnership with McKee and Manmeet and Richard as a team.
We were very pleased in the last few months to add Maria Sainz as an independent director. She has a wonderful career in med tech as both a senior executive and chief executive officer and a director, most recently having served and assisted in the development of Shockwave up through its sale to Johnson & Johnson. From a financial perspective, we have cash on hand ending last year at $80 million. We are using that cash to run our clinical trials and expect to have more than sufficient cash to run all of our trials and complete enrollment through 2026 and into 2027. We are or at least have been running at about a $15 million quarterly burn.
We expect that to go up in Q2 and Q3 as we ramp those clinical trials. All of our capital is being invested toward those strategic objectives to create increased shareholder value. We have been in possession for the last several weeks, as some of you may have seen, extraordinarily, maybe unprecedentedly positive data on the treatment of atrial fibrillation. We'll talk more about that, in light of those data points and how that market impacts all of med tech, we're not surprisingly increasing our focus on our EP program, and we'll again spend more time there momentarily. Let's just talk about pulsed field ablation as a energy evolution and how NSPFA fits in.
If we think about ablation typically starts on the far left-hand side here thermally, introducing extreme temperatures to destroy unwanted tissues and using radiofrequency most commonly, but other forms, whether it's microwave energy or high-intensity focused ultrasound, all for the purpose of burning tissue. Burning tissue can ablate unwanted zones but also introduces significant clinical risks and downsides associated with how those thermal zones propagate and can touch and disrupt areas that are not desired and cause safety or adverse effects. First generation PFA, embodied perhaps most notably by Farapulse, has been introduced in the last several years and has shown the potential of using pulsed electric fields to create pulsed field ablation.
In that case, using microsecond bursts, so relatively long bursts of energy, at relatively low, energy levels of perhaps, 2 to 2.5 kilovolts. That has the capability of creating permeability in cells and ultimately destroying tissue non-thermally. Most importantly, though, that is a first generation of technology, and over the past number of years, Pulse Biosciences has accumulated both the intellectual property estate and the technology capability to develop and now bring into the clinic and produce outcomes with Nanosecond Pulsed Field Ablation. Nanosecond Pulsed Field Ablation operates with pulse durations that are measured in billionths of a second. Not only does that seem to all of us to be extremely short, but most importantly, it is a 1,000-fold shorter than a microsecond pulse that might be delivered from a conventional or first-generation PFA system.
You think about advancing the technology, by leaps in pulse duration and then compounding that much shorter duration pulse with a much higher energy delivery. It is that magical combination of much shorter pulse durations, much higher amplitude that creates a much more energy-efficient pulse, lower total energy delivered into the body, decidedly less thermal and really non-thermal in its footprint, and inducing an entirely novel form of cell response in the form of regulated cell death that is essentially an implosion of the cell, not an explosion of the cell. We think we're in possession of something extremely novel and it is protected by one of the most impressive patent moats, I think, in the history of medical technology. We have a patent estate of 250 patents.
That number continues to grow, and it covers systems and applicators and methods of delivering energy. If you think about this as a generator moving through connectors, moving through to catheter systems and ultimately electrodes at the distal end, we cover the technologies required to deliver short, high-energy bursts at every juncture along that chain. That produces a very impressive hurdle that we think would be extremely difficult for any other company to try to overcome. If you think about this as an important energy wave, if you think about this as possessing the potential to change clinical outcomes in very large markets such as AFib ablation, and if you combine that with this impressive IP portfolio, one would get the sense that we can be a leader unto ourselves in NSPFA delivery in major markets for the foreseeable future.
Let's talk about EP as the first and most important clinical indication. I think everyone knows atrial fibrillation is the single most common arrhythmia in man. It has converted into a very high prevalence and increasing incidence disease, so it's growing. We're finding it more often in a population that has more commonly been afflicted by AFib based on how we age, how we've grown, if you will, older with hypertension and other cardiac morbidities that produce AFib. That has produced a very large market, billions and billions of dollars in the interventional treatment, many more billions being consumed in drug therapies that are generally not that effective, ultimately converting into nearly 2 million annually diagnosed patients.
Of course, the goal is to move those patients through their diagnosis and into treatment as an effective treatment, which drugs generally are not, as early as possible in their guideline-directed therapy. Our system is compelling in how it will, we believe, revolutionize AFib intervention, and we start with lesion quality. The pulsed electric field that our catheter delivers, as evidenced by that image on the upper right-hand side, where you see multiple colors and a line that essentially, it represents the full circumference of what would be a pulmonary vein. We deliver in 1 single 5-second lesion a contiguous array of energy that penetrates the tissue, creates a full thickness or transmural isolation of electrical conductivity, which turns off AFib in that vein.
When you think about lesion quality, this is unparalleled in the practice of PFA. Speed is one of the benefits, we have extraordinarily short treatment times. In as few as 5 minutes, a full pulmonary vein isolation can be completed, and that can be done within a skin-to-skin time with that patient on the table for as little as half an hour. These are dramatic improvements in time compared to current practice. The workflow is highly consistent. It's really drop-in consistent with the way procedures are currently performed. Our catheter in the upper right-hand side, and you can see small electrodes on each of those splines. Those electrodes allow us to map, and ultimately this creates a single catheter workflow potential where we can map and ablate with 1 device.
From an efficacy perspective, we'll get into this now momentarily, but we have now produced 12-month follow-up data that is unprecedented in its premium benefit to the patients. That is being converted now from European feasibility study data, which is not only impressive and growing, but to be complemented by our IDE, which has been approved and will commence enrollment in the next few months here in the United States. Just bringing this a little bit more forward in terms of how the procedure works. You see there two images, an animation on the left and an angiographic image on the right.
You see that open array of our electrodes is inserted into a pulmonary vein and inverts to put the two ring electrodes in contact with the vein. A singleA train of pulses that lasts only 5 seconds is delivered in that vein and creates complete circumferential isolation in that 5-second period. Moving to the bottom of the slide, we would pull that catheter back out to the antral position, which really covers the mouth of the vein, deliver 1 more 5-second ablation. In that workflow, you can imagine it takes a few seconds to place the catheter in the vein, a few seconds to ablate, a few seconds to move it out, a few seconds to ablate. You can finish 1 vein of the 4 in literally 1 minute.
You move immediately adjacent to the next side-by-side vein, do the same thing, and you can complete all 4 veins, and as I've said, in a matter of 5, 7 minutes, depending on your speed focus. Whether you then prefer to go and put an extra lesion at the carina or in the posterior wall, total aggregate time to invest in an extra lesion or 2 or 3 is extremely limited, and that allows comprehensive PVI procedures to be done faster than any other procedure currently available or forthcoming. Just to give you now a sense of the data that we have produced, and on the left-hand side, you see a chart. This is taken from the AF Symposium, where Dr. Vivek Reddy presented our outcomes data.
Let's focus on that central column, which is our selected final dose, 5-second dose delivery. You see of 150 total patients treated, 114 patients received that dose. Go all the way to the bottom 2 lines, and you see at 6 months, followed with rhythm control outcome. How are these patients doing without reintervention, without the need for a pacemaker, without the need for cardioversion, without the need for antiarrhythmic drugs? 100% clinical success at 6 months and an unprecedented level of 96% clinical success at 12 months. You also look at the right-hand side of that graph, and you see the further column over to the right is a combination of pulmonary vein isolation plus posterior wall. This is a slightly more complicated patient group.
They needed a few extra ablations. Down at the bottom line, you see 100% clinical effectiveness against that primary endpoint of rhythm control at 12 months. These data are really unique in the field of atrial fibrillation therapy. On the far right-hand side, you see a Kaplan-Meier curve, which is a higher bar. This is any form of atrial arrhythmia, tachycardia, flutter, fibrillation, measured not just by a 24-hour Holter at the end, but by event recorders or telemetry monitoring over the course of that span of time. You still see with a broader definition and more hunting for arrhythmias, you still see 90% effectiveness at 12 months. Our job now is to advance this program forward into the IDE and into a technology development program.
This gives you just an example of what we're working on next. If you see on the left-hand side, you see that array of 2 electrodes. That's our current device, which creates a very broad zone of ablation energy delivered into the pulmonary vein or against an atrial surface. On the right-hand side, you see the embodiment of our next-generation catheter, which we'll call the Epicenter Plus, which will incorporate not only the regional ablation of the first-generation device, but a large footprint focal ablation element in the center of that device, which would allow for either regional or focal ablation to be done by the same tool.
As I mentioned previously, based on the array of sensors that we have, this then becomes a regional and focal ablation and mapping tool that would enable an entire AF ablation procedure to be done with a single catheter, no catheter exchanges, only further improving the speed advantage that we've demonstrated to date. We are not just an AFib company for EP. We are working on other programs. We have announced previously our cardiac surgery program, which is a surgical clamp to be used in concomitant ablation for patients that have AFib undergoing open heart surgery. That is a program that has been advanced. It's received Breakthrough designation by the FDA.
We have commenced our IDE and are enrolling that study now and expect to complete that enrollment in 2026, as we will the US IDE for our EP catheter. We are also pursuing novel solid organ opportunities, including the thyroid as an example, which is a target that can be preserved from organ-removing surgery with a minimally invasive approach using nanosecond PFA. There are tremendous clinical benefits here. This is an early market that has market development traits. We're investing in data. We're investing in regulatory approvals. We're investing in reimbursement. This is a market that we think has the potential to be quite sizable.
Then we are also looking at other markets, including, which we'll announce in the relatively near term, commencement of our first clinical study in an oncology indication, treating what will then be papillary thyroid microcarcinoma. That's an exciting first oncology application, which we'll provide more information on later and is coming to us through our partnership with MD Anderson. We think about our plans for 2026 and wrapping up our story here before we go to Q&A. This is an extremely exciting time for the company. As you see here, first and foremost, we're focused on the electrophysiology application. We have already demonstrated unprecedented speed, workflow simplicity, and now clinical evidence of durability, which is remarkable and has really turned, I think the sights of the industry toward us. That evidence will continue to evolve.
As is mentioned here, we will provide an update, based on our acceptance just recently, as a late-breaking clinical trial presenter at the HRS meeting, which will be only 2 months from now. Our goal is to commence and complete IDE enrollment in EP this calendar year, 2026, and to advance not only catheter development here in our labs, but also a continuing array of clinical evidence development in our expanded European feasibility study. On the cardiac surgery side, as I mentioned previously, we'll advance our IDE enrollment with goals to finish that this year. On the soft tissue ablation, all elements of market development, particularly focused on data and regulatory advances for that first use case of a soft tissue ablation. Lastly, this is Pulse, I'd say, in a snapshot.
Very novel energy, taking advantage of all the benefits of PFA while truly creating a novel form of PFA. Taking advantage of nanosecond pulse durations, high energy, a very unique form of energy that has a unique mechanism of action on tissue. As mentioned, highly protected, unprecedented level of intellectual property ownership for this company. 250 patents covering the entire array of energy delivery end to end. Mounting clinical evidence. The data that we presented at AFS. We'll have more data out literally this weekend on thyroid applications from a conference in that clinical segment.
The EP durability data will continue to grow as we follow those European feasibility patients out through their 6 and 12-month all the way through to completion as the number of patients begins to exceed 150, and all of those patients reach their 1-year follow-up. The markets that we're going after are extremely significant, headlined, of course, by the multi-billion dollar opportunity in electrophysiology and in particular, the ablation catheter market alone at probably $3 billion-$3.5 billion today and growing, as you all know, at 15%-20% compounded annually. We have many indications in the pipeline, which we are pursuing while focusing principally on EP. We have significant clinical activity in 2026, including parallel path IDEs for ablation of AFib in surgery and in EP.
We have the cash on hand to complete those studies this year. With that, Josh, I'd be happy to end my prepared comments and answer any questions.
That was an impressive presentation, Paul. Thank you. Impressive technology, impressive progress.
Thank you.
Congratulations on all the above. wanted to start on Enpulse and cardiac ablation. First of all, just, I mean, on the waveform, I know you guys have a unique patent-protected nanosecond PFA technology. I mean, how challenging was it to arrive at and select this waveform and it is so proprietary. We've heard from clinicians about preclinical work and just the quality of the lesion that's generated by Enpulse. I mean, just in terms of thinking about how differentiated and how can someone even try to replicate it or get even close, I mean, that's gonna take a lot of work. I'm not an engineer, but maybe someone like that.
Yes. Well, good question. We think about this all the time. We are a young company, but we're 10 years in the making, right? This technology, if you go all the way back, nanosecond pulsed field ablation or nanosecond pulsed electric field, has been in the development if you go all the way to academic research physics labs for 15+ years. It's been published in scientific literature for that long. Our company, Pulse Biosciences, aggregated technologies directly out of universities and turned that into both an IP estate, which is so unique and broad, as well as a technology development program.
If you think about the company having been formed in the 2014, 2015 timeframe and roll that forward to today, all of that time has been on refining the generator, developing the applicators, catheters, surgical tools, percutaneous electrodes. To your point, the pulse parameters associated with one tissue type after another, after another, so that we can then move into multiple clinical applications. As I mentioned on the 5-second duration pulse train that we're using in EP, we can go straight from the preclinical model right into the clinic and generate superior clinical outcomes first time. I think that speaks exactly to how hard it has been, how long it has taken.
It's a combination of all of that IP, all of that hundreds and hundreds of preclinical studies in different tissue types that allow us to now have multiple IDEs. This is a very, very uncommon approach for an early-stage company. I would say if one were to try to replicate that, there's that twofold barrier, right? The first barrier is that every element of creating and delivering ultra-short duration, ultra-high energy bursts of electricity requiring electrical engineering technologies, all of those elements of energy delivery are patent-protected. It's not that you just need one design around, right? You would need 20 design arounds of 20 different impediments. Every part of that would have to be converted into a successful clinical program that we've been working on 6, 7 years in arrears.
Which would say that if you wanna try to replicate this, it might be years and years and years of overcoming technology and intellectual property barriers.
Thanks for that. The fruit of all that labor you described, came to bear at the AF Symposium for Enpulse cardiac ablation system, with the data that you showed here today again. I mean, back to the waveform and the lesion creation. I think you answered this question on the earnings call and just saying this is maybe internally expected to get the procedural success rate at 6 months, 12 months, and then the 90% recurrence-free rate that's been posted, because of the technology, because of the lesion, the proprietary lesion creation capabilities. Anything to build on that?
I know you answered this question already maybe last week or the week before, I'll hand it off to you.
The data are. They're unprecedented because if you think about tissue, we treat tissue with ablation. We treat tissue with Pulsed Field Ablation with conventional systems, and we still see failure rates that are 20%-25% in the real world. We see real-world reintervention rates at a year of 20%-25% or even higher. That tells you that there is a fundamental weakness in current energy delivery. We know our energy delivery is far more efficient, far more therapeutically potent, and we have seen that in study after study after study. I will say it's a high bar in medicine, Joshua Jennings, as you know, to produce 100% anything. The notion in this complex structure of the heart, everybody's anatomy is different. Everybody's rhythm system is different.
We're trying to universally approach them with pulmonary vein isolation. To have that work 100% of the time, given the variation from patient to patient, from physician to physician, from site to site. Given early-stage mapping integration, where we were not any really providing the physicians with the clarity of precise catheter placement that they're used to with a fully integrated mapping system. Taking all of those variables into consideration and then still delivering 100% 12-month success for PVI plus posterior wall, that's it's hard to comprehend how that can be given all of the constraints of really making this procedure as effective as we'd like it to be. I would say we dared to dream. We thought we would do really well.
One typically doesn't start a clinical trial with all those human variations and expect 100%. To be at the level that we're that we've achieved so far is very impressive. It's obviously it's a testament to the team and the technology. I will only say our physicians, when they look at the 96%, they say, "This is unimaginable for other technologies. It's hard to imagine how strong this therapeutic potential is for you, but we actually think we can do better when it's integrated finally with with mapping clarity.
That's a great point, and hopefully there's time to just talk about mapping integration. Before that, the data presentation at the AF Symposium by Dr. Reddy certainly turned heads in the EP world, and we experienced that real-time this week with our a panel of electrophysiologists in the Boston area that we've been checking in with regularly over the years. If we had had the same discussion in the fall and last spring about, you know, their outlook for Enpulse cardiac ablation, you know, they would have kind of shrugged their shoulders and or they did actually shrug their shoulders to a degree, not exactly. Just, you know, we'll see and didn't have much feedback.
At this conference, March of 2026, post 2026 AFib Symposium, there was some, I felt to be some, real optimistic and enthusiastic feedback. That's real-time feedback for us, and I know you've described some buzz that's been generated since that data presentation in the EP community and with your investigators. What are the next steps that are left, speaking of investigators, for before you start enrollment? It's just IRB approvals and just getting all the administrative work now that the IDE approval is in hand.
That's right. Well, thank you for those comments. I think the buzz is real. I think the investigator enthusiasm is real. Data, of course, this is a highly scientific clinical community. Data drives everything. I think they really appreciate that you cannot, you can't back into 90%, right? This is real, and it's, and there have been so many studies done prior to this that have never come close. There's something clearly categorically different here, and of course, it is the NSPFA energy. When we think about mechanically now initiating the IDE, it's exactly as you describe.
We only received IDE approval the 19th of December. The 1st week of January, we were back contacting those centers, getting going with their local IRB approvals, contracting them, getting sites up and running and ready through their site initiation visits. All the things to assure incredible rigor, compliance, and quality of the data. We wanna make sure, you know, in the haste makes waste kind of theme, that we are doing this really in a intensely focused way, making sure every site is ready to go. We're within a matter of weeks of that happening, and we'll announce when we enroll the 1st patient. If this is...
I think it's a combination of speed to get going, but intense focus on quality at every site, making sure every investigator in our new, let's say 20 centers in this study has the ability to produce the same quality data that we have seen coming out of the European feasibility study.
Maybe I'll sneak one question here in. One last one here with the red light flashing on the clock. Just to circle back to your reference to potentially, IDE results getting better coming in better than the early feasibility study because you'll have mapping technologies in play and Enpulse will be integrated. Maybe just build on that. I know this was addressed at the AF Symposium on your earnings call, but I think it's another important point, along with many others that we're not gonna get to, but to address here at the TD Cowen Conference.
Well, we're, when we start with 100% effectiveness in certain categories, we start with 96% effectiveness in certain categories. Of course, there's no room to grow.
To get better.
Right. We don't, we don't intend to convey that we expect higher numbers per se. However, when you go into a study with more centers, more hands, more variability, anybody... I've done dozens of IDEs. Anybody would be concerned that there's the potential to introduce dilution of clinical effect because of that. We look at it and say, "Actually, we certainly wanna ensure that we don't allow any dilution of effect, but on a per case basis, based on higher granularity of catheter placement, based on the evidence that we've seen so far about our workflow, right, two lesions per vein. If we do that well, our physicians know they can deliver exquisite results." And I think that's our goal, exquisite results, to try to replicate the success that we've seen in Europe.
I think the other thing that folks should understand is that we are not taking a small scale study and trying to now scale it in the U.S. and hope to reproduce. We're taking a large scale study. We've treated more patients in Europe than our target enrollment in the United States. We're not actually scaling. We've already had multiple centers and nine operators, some of whom will be the same operators, from Europe, participating in the IDE. Many of the variables allow us to project that our results should be equally impressive coming out of the IDE.
Appreciate that, thanks so much for the time this afternoon. Good luck with the meetings the rest of the day, thanks again.