Good morning. Thanks for joining us again at the 25th Annual Needham Healthcare Conference. I'm Mike Madsen, and I lead the MedTech and Diagnostics Equity Research Team at Needham Company. I'm pleased to introduce Pulse Biosciences. Presenting for Pulse today, we have CEO Paul LaViolette and CFO John Skinner. They're going to give a presentation on Pulse, and then we should have some time for questions at the end. If you do any questions you'd like to ask, you can submit them electronically through the Needham Conference website, or feel free to email them to me at mmadsen at needhamco.com. So with that, I will pass it to Paul and John, and I will come back at the end to facilitate Q&A.
Thanks so much, Mike. We appreciate the introduction and the invitation to join you and the team here at Needham. So good morning to all. It's a pleasure to present on behalf of Pulse Biosciences today. As mentioned, my name is Paul LaViolette. I'm the chief executive officer, and I have been in the medtech industry now for over four decades. I've had an opportunity to work on many impressive and important and disruptive technologies, and certainly my observation is that pulse biosciences is at the top of that list, bringing extremely unique and proprietary nanosecond pulse field ablation energy to the field of electrophysiology and to a number of ablation targets thereafter. John, if we could go to the next slide. We'll be making forward-looking statements today, and here is our claim on that regard. And then next slide on our mission. We're very focused on three key points. First and foremost, our exclusive mindset in and around the development of nanosecond pulse field ablation energy. This is a very novel energy in the pulsed electric field domain. All of us have seen the impact in the last several years of PFA, pulse field ablation, in particularly the field of atrial fibrillation management. That's a very large, fast-growing, prominent marketplace. We'll talk more about that. Pulse Biosciences is the developer and owner of a range of technologies and intellectual property supporting a very novel form of PFA energy. And that is our exclusive focus, and we'll spend more time talking about how we're developing that clinically and over time in different market applications. The second point to make is our conviction about rigor in development. The company has been in existence now for over 10 years, has been investing aggressively in the development of this energy form, and has developed a massive trove of preclinical evidence and has now moved into multiple clinical trials and clinical segments developing very important scientific evidence about the effects of this novel energy on tissue and on treating patients with chronic conditions. So we're very focused on generating data. I think we've generated more data than would typically be expected for a company of our scale. And I think you would say the same thing about our intellectual property estate, which we'll talk about as well. And then lastly, I really want to talk about our ability to impact patients and the marketplace and all of its constituents, including providers and physicians and ultimately payers. We have a very strong, I'd say visceral commitment to our mission clinically. And we know that if we do the right thing technically, clinically, for our physicians, for our patients, that we have an opportunity to be very successful in creating value for our shareholders. So we have a very, I think, high order mission. And based on our track record, I think we've demonstrated that we're very capable of delivering on these goals. Next slide, please, John. On the team, as I mentioned, I've been doing this for a number of years both as a large company operator a ceo and a private equity investor all in medtech with a number of wins a number of major market launches and my view is that pulse will be the the capstone of that that long career this company is really founded on an exceptionally strong technology base and that technology base is led by darren euchre darren is our chief technology officer, has really been with the company since its founding and is principally responsible for the direction of the technology and the conversion of that technology into clinical practice. John joined me just a year ago as chief financial officer as we've, I'd say, increased our public company presence. And then let me spend a minute talking about two important new additions to the team. Leanne Toplitsky has joined us only in the last week as chief operating officer. Leanne has a very pronounced career, a number of years in electrophysiology as a technologist, developing hardware as a sales executive, first at St. Jude and then in through to Abbott, moved on to become a general manager at Zimmer Biomet, a chief executive officer for early stage med tech companies. Leanne joins us as we scale our efforts in execution and as we shift our focus increasingly toward the effective execution of our EP program. So her deep background in EP, her fantastic track record as an operator joining this very strong team is a perfect addition at the perfect time. I also want to highlight, as I have in the past, the strength of our chief medical officers, but most importantly today, Dr. David Kenningsberg, whom many know as a key opinion leader, electrophysiologist, and most recently as our part-time chief medical officer has joined the company on a full-time basis. Of course, coincident with the launching of our IDE clinical trial in the United States. And so we're very pleased to have this new, extremely potent combination of Leanne and David joining our ranks. And then lastly, our board of directors remains remarkable and a secret asset, if you will, for the company. I've mentioned previously, Maria Sens joined us most recently. Maria, also a very experienced operator and CEO in MedTech, and most notably, a recent member of the board of directors of Shockwave up through its sale to Johnson & Johnson. So Maria brings fantastic perspective, governance, and operating experience. And then, of course, Bob Duggan is our North Star. Bob, a legendary investor and entrepreneur, had the vision to back Pulse Biosciences 10 years ago. Bob has been remarkably successful both in medtech and in biotech, and his daily interactions with us bring inspiration, operating insight, and energy that is unmatched. Next slide, please. As we think about just our current financial snapshot, we ended 2025 with approximately $81 million of cash. We had $54 million of cash utilization in 2025, or approximately $15 million a quarter. We've indicated that for 2026, that burn rate will increase slightly as we intensify our operating activities with the performance of an IDE, both in cardiac surgery and in EP. And so our burn will increase throughout the calendar year, peaking later in the second half of this year as we peak our clinical enrollment activity. We have adequate capital to perform all of our objectives for 2026. And we're very pleased to have the financial support, both of our insiders and the capability to execute the game plan that we have, which is exceptionally exciting. John, next slide, please. Let's just talk for a minute about nanosecond PFA and energy forms overall and the market for ablation technology. So I think everyone is aware that ablation emerged over the last number of decades as a means by which to treat tissues without surgery and to really drive the creation of minimally invasive therapies. And those therapies span all forms of conditions targeting different organs across the full range of the body and chronic disease. Thermal ablation takes tissue out with extreme temperature, more often high temperature, but you're also aware of cryoablation on the low And this can effectively destroy unwanted tissues, but does so first and foremost by ablating, I'll say, everything in its path, right? All tissues, be they cellular, non-cellular, connective tissue, vessels, nerves, everything is ablated in the field of that thermal zone. and that thermal zone is difficult to control and therefore there is an inherent safety risk associated with introducing and applying very high temperatures to a targeted zone and then potentially incurring the risk of having that therapeutic zone reach beyond and touch areas that should be protected. And so there are basic limitations to thermal ablation, although it is used tens of millions of times. Along came in 2023 the first application of pulsed electric fields. Pulsed field ablation was introduced at the end of 23 and through 24 and 25. We saw it have a dramatic impact on conversion of radiofrequency thermal ablation in electrophysiology over to a non-thermal application. and this first generation of PFA demonstrated the potential for what PFA can do to therapeutic markets. There are limitations, however, to first generation PFA. It is generally referred to as microsecond PFA, so the pulse durations of those pulsed electric fields are measured in fractions of a second, and those pulses in this first generation technology are relatively long, And they affect the cell by introducing permeability in the cell and causing those cells ultimately to die. There is a careful balancing act between the non-thermal and thermal boundary of PFA. And in order to stay non-thermal, first-generation PFA requires relatively limited delivery of total energy, relatively limited footprint of ablation zone, and often a lot of catheter manipulation and overlapping and stacking of lesions in an effort to create a more comprehensive ablation area based on the limitations of those first-generation pulses. Now let's move to nanosecond PFA. First and foremost, this is an energy that benefits from the pulsed electric field value. It is intended to be entirely non-thermal and to ablate cells using electroporation. But in addition, it's a far more efficient way of delivering energy. And as a result, by collapsing the duration of the pulse by as much as a thousandfold from a microsecond or a millionth of a second to a billionth of a second, we give ourselves the potential to dramatically alter the overall energy parameters delivered. Offsetting the extreme shortness of that duration, we add additional pulsing energy in the form of a higher amplitude, and that higher amplitude plus that extremely short duration provides us a very unique formula for delivering pulse electric fields that allows us to deliver energy more efficiently, deliver it over a broader surface area, and deliver it in a workflow that is unmatched by any first-generation PFA. Next slide, John, please. When we think about the novelty of that technology, it's important to understand that first-generation PFA, as practiced by today multiple competitors, for instance, in the electrophysiology field, that first-generation PFA is clearly relatively open source because multiple companies already sell it within the first few years of its introduction into the marketplace. What's really differentiating about Pulse Biosciences is that Pulse Biosciences has gathered and created all of the technologies necessary to generate and deliver nanosecond pulse electric fields at high energy from the generator down through connectors into catheter systems, out electrodes, and into the tissue. We have a very extensive patent portfolio covering multiple facets of the generator, the delivery systems, and all technologies necessary along that continuum of pulse delivery, which allows us to believe that we will be the sole company participating in the NSPFA category on a go-forward basis. And so with that potential, Let's turn our sights on the next slide to our commercialization and market access strategy. First up for us is the electrophysiology market treating atrial fibrillation. Everyone understands AFib is the number one most commonly diagnosed cardiac arrhythmia, and it is growing. It is growing rapidly because of the demographics, because of the health of our population, because of the presence of earlier diagnostic tools, and because of the prevalence of early ablation capabilities to treat early stage AAF, known as paroxysmal AF. These elements combine to create an extremely attractive $3 billion U.S. catheter market and a multi-billion dollar larger worldwide catheter market and overall AFib market. When you think about diagnoses, This is multiple millions of new diagnoses per year, and the most important, I'd say, attribute of this market is that it is highly amenable to new technologies, and we've seen this market really be upended in the last 24 months based on the introduction of a PFA technology that offers speed, workflow ease, efficiency, safety, and really, as of yet, no improvement in efficacy. With that, John, let's look at the second or the next slide and talk about how nanosecond PFA can change that once again. Nanosecond PFA is known and demonstrated in our large data set so far, particularly the acute data set for lesion quality and speed. We are capable with our energy efficiency of delivering only a single lesion where a competitive technology, let's say the market-leading PFA technology from Boston Scientific, the Ferrapulse technology, that technology would be required to deliver four or five or six lesions in a given location to create a circumferential isolation. Our energy is capable of delivering a fully transmural lesion in five seconds with one application of energy, and that fundamentally redefines the workflow of the procedure. You see that evidenced in that finite element analysis image on the upper right-hand side where you see that red band. That's an example of a fully transmural energy wave being delivered through, in this case, that conical zone, which would represent the osteal area of a pulmonary vein. Speed is our differentiating factor. we have the ability to deliver fewer lesions, five seconds apiece. And so total ablation time can be as low as five to seven minutes for these procedures. Workflow is enhanced dramatically. If you look at the catheter on the upper right-hand side, the zone between those two rings is the entirety of our ablation area. And on each of the five arms that supports those rings, you see multiple sensors. So we have the ability to map and ablate with the same catheter. We have the ability to ablate large footprint zones. We have the ability to minimize sedation areas because our pulses are in the body for so short an amount of time that we ultimately envision this technology being ideal for a shift in site of care from the hospital into the ambulatory surgery center. So overall, this is an exceptionally timely and I'd say ideal market fit technology in the EP ablation space in 2026 and for the next five to 10 years. To support that, we're enrolling our IDE now. We'll talk about that a little bit more momentarily. Next slide, please, John. I just want to bring this a little bit more to light, and then we'll go into the details. On the left here, you see an animation. On the right, you see a fluoroscopic image essentially representing the exact same placement of that catheter. As simple as this appears to be, you enter the left atrium, you enter one of the four pulmonary veins, you place the catheter into the vein, those arms invert into that mushroom configuration. The two electrodes create a bipolar zone with five seconds of energy delivery between those two electrodes, and you have a single transmural contiguous circumferential ablation of that pulmonary vein. You then pull the catheter back to the antral position at the mouth of the vein, repeat that same five-second ablation, and if you think about it, enter the vein, ablate for five seconds, manipulate the catheter, ablate for five seconds. Really, you're treating an entire vein in under one minute, and given that there are four veins and it takes a little time to move from one to the next to the next, you can imagine how we land on our five, six, seven-minute total ablation time outcomes. And it's really unprecedented in this space and has the potential to increase the treatment potential of the market, increase the efficiency of every trained electrophysiologist and the throughput of every lab. This can really be a dramatic upending technology in the AFib space. Next slide. As I mentioned, unprecedented workflow and speed and ease of use have been enough so far to change the marketplace. However, we have much more to offer than that, and we now are in possession of long-term follow-up outcomes that for the first time indicate that a new energy, in this case NSPFA, has the potential to improve long-term clinical success. And so on the left-hand side here, you see a chart of data presented at the AF symposium in February, and in the middle column, you see the most representative data set for our technology, which represents a five-second data set treating patients with paroxysmal AF. And at the bottom highlighted, you see that at 12 months following the same endpoint used by pivotal studies in the U.S., which is to say 24-hour Holter monitoring to detect AF, we had a 96% success rate, which is to say 12 months freedom of atrial fibrillation off antiarrhythmic drugs and not having required cardioversion or a rhythm control. On the right-hand side, another look, potentially even more influential, which is all atrial arrhythmias, flutter, fibrillation, tachycardia, measured by all forms, including not only 6- and 12-month Holter monitors, but also weekly telemetry monitoring using in-home ECG monitors. And this shows 90% freedom from all atrial arrhythmia throughout the course of that 12 months. And obviously, both the 96% AF freedom and the 90% Kaplan-Meier curve result of freedom from all arrhythmias are substantially improved upon any real data set ever demonstrated in the catheter ablation space for AFib. Next slide, please. We mentioned about a month ago that based on the compelling nature of these results, we were going to increase our emphasis on EP among our other programs. And so that emphasis comes in the form of investing to accelerate our IDE. Important to that, as I've already mentioned, are the additions of Leanne and Dr. Kenningsburg to our leadership team. We have previously described our IDE as having started now in April and expected to be completed in enrollment by the end of the year, and throughout the course of this year, we'll update you on that progress, but our goal is to accelerate that with increased focus. We also intend to continue to expand our clinical evidence using the feasibility study in Europe. Our goal there is to continuously broaden the data set, and importantly, because of the open-label nature of the study in Europe, continue to provide follow-up data on a kind of a real-time basis throughout 2026, so that we can see more and more data accumulate for longer and longer periods of follow-up, validating with increasing concreteness the quality of our long-term outcomes. And then lastly, we'll talk a little bit in a minute about our increased intensity of product development. On the next slide, just a little bit more detail on the IDE. As announced earlier this week, we have performed our first patient in St. Bernard's Hospital in Johnsboro, Arkansas, very successful first day, seven patients treated. And I think this highlights the nature of the nanopulse study and of the epicenter catheter from Pulse Biosciences. This is a first-time operator, obviously very experienced overall in AFib ablation, but first time utilizing the catheter, one role inpatient, followed by half a dozen study enrollments, all done in the first day. This would be a remarkable day in any lab using any technology, but to do it first time with a team that has not used this technology before highlights the speed and alacrity with which labs will be able to use the Pulse Biosciences technology to transform the efficiency of ablation delivery in the future. Next slide, please. When we think about our technology development goals, the image on the left, that light blue circle, that's our current device. That is the device entering the IDE. And it indicates that the ablation zone is the area between the circular electrodes. That is a very large, we'll call that a regional ablation footprint. And that provides tremendous operating capability in the lab. And then we also had developed a focal catheter, which is a way of delivering the same pulse field ablation energy on a point-by-point basis. To make it abundantly clear, the best of both worlds would be to have those two energy delivery capabilities in a single delivery system. A single catheter will be able to deliver both a regional ablation zone and a focal ablation targeted lesion without having to change catheters. And because these catheters also have sensors to map, you can imagine a single catheter capable of doing regional or focal ablation, capable of doing ablation and mapping. So a single catheter workflow could allow you to ablate the veins, move around the atrium, perform extra venous lesions, and perform the entire procedure without changing devices. We think this is the kind of innovation that has the potential to really upend the entire AFib ablation market. Next slide, just a closing couple of comments on the rest of our platform. As you are aware, NSPFA has the potential to go in many directions. We're very pleased to have commenced an IDE enrollment for cardiac surgery. Cardiac surgery, of course, in this case is also treating atrial fibrillation in the manner of concomitant ablation. So when a patient with AFib is undergoing some other form of cardiac surgery for coronary bypass or valve repair or replacement, if they have AFib, it is guideline-directed that those patients should also receive ablation to treat their AF. That presents a significant market opportunity. And most importantly, that market today is served by only radiofrequency technology. And so with the advancement of our platform into the IDE stage, we have the potential to redefine that market and also to be the first PFA entrant into that category. So we're very pleased with the data that we've seen so far and also have the objective of enrolling this IDE study in 2026. We also have an array of soft tissue organ ablation targets that are already FDA cleared, the first of which is for thyroid. We're in the market development phase of that technology. Thyroid disease focused initially on benign thyroid nodules represent the cause of as many as 150,000 surgical removals of the thyroid every year in the United States. We think that represents a significant opportunity for a minimally invasive alternative using NSPFA in the thyroid to ablate nodules while leaving the thyroid functioning and in place. So the ability to offer a patient a thyroid sparing alternative to thyroidectomy, we think is compelling, and we're working on data reimbursement, an expanded FDA label to bring that technology to the fore. And we also have a number of other indications. We're trying to stay very focused. We're prioritizing EP, but we're extremely enthusiastic about the downstream benefits of this technology, particularly in cancers. We announced a strategic relationship with MD Anderson and the initiation of our first clinical trial treating papillary thyroid microcarcinoma. And we believe that will be a study also enrolled in 2026 and the first of many breakthroughs for cancer patients leveraging this technology. Next slide, please. Just wrapping up, here you see a summary of our activities, if you will, for the year, principally highlighted by the electrophysiology study, perform the IDE, continue to release data, continue to advance our data generation in Europe, and continue to advance our R&D platforms. And then, of course, as I've just mentioned on cardiac surgery, enroll that IDE, and on the soft tissue ablation side, continue to generate evidence to advance the reimbursement and regulatory prospects of that business while treating in a very pilot sort of way commercial patients who would prefer to have NSPFA rather than to lose their thyroid to a thyroidectomy. And then a closing comment, and then I look forward to answering questions. This is an extremely compelling story. Nanosecond PFA both capitalizes on the benefits of pulse field ablation while redefining the energy fundamentally. And we have a growing body of evidence to demonstrate exactly how compellingly different NSPFA is from precedent microsecond technology platforms. As mentioned, this is proprietary. We own a very vast estate of IP that would make it very difficult for anyone else to replicate our technology. We have a growing level of evidence demonstrating clinical benefits of this energy platform the goal for this year is to drive more data both leveraging the data coming out of europe and then supplementing that with our ide data we have a number of markets that we're targeting the most compelling of which and first up if you will will be that very attractive ep ablation market for afib with a number of indications that we're pursuing uh already uh to follow on. And we have the capital in hand in 2026 to execute on that plan. And we're very pleased with how 2026 is shaping up so far. And with that, Mike, I'll end my comments and look forward to answering your questions.
Yeah, thanks. So I guess, you know, first starting with the catheter business or product. So, you know, you announced the total trial. So can you maybe just talk about the design of the trial and how it compares to the other prior precedent trials from your competitors.
Yeah, so the trial is a single-arm study enrolling paroxysmal patients, treating them with PVI or pulmonary vein isolation. In that regard, it's a relatively straightforward application of energy for a very large patient population. And by that, I mean to imply very high flow of patients and should enroll on a site-by-site basis relatively quickly. We're approved to go to up to 30 centers, although we will probably not reach all of those by the time we complete enrollment. The N of the study, the target N, is up to 155 patients that would generate data to be evaluated, if you will. The statistical plan is on 145, so we end at 145. But, of course, if there are patients in the queue, we can exceed 145 and go up to 155. So we'll enroll between 145 and 155 patients that will be evaluable, and then each of the centers has up to two roll-in patients, which is how the number can exceed 155 and get up to 215. If you enrolled 155 plus two per 30 sites more, you'd add 60 to the 155. So we'll ultimately enroll 145 to 155. The endpoint is focused on six months, but is, I would say, enriched by a portion of the patient population that will be followed by 12 months. And then we'll blend those two data sets using Bayesian analysis to end up with a 12-month endpoint as predicted by a combination of six and 12-month follow-up.
Okay. All right. Right. And so based on that, how long do you think, could you, how long, how much follow do you think you'll actually need? So it's over between six and 12 months effectively, like, but you probably can't really predict exactly where it'll fall or.
Well, I think the way to think about it is the first patients through who are earliest in the study will be followed the longest, right? So the first patients through will be followed for 12. And so if you think about enrolling 20, 40, 60, 80 patients, follow those patients for 12 months. And so the faster we can enroll the first tranche of patients, the faster we get to the point where we start that 12-month clock, if you will, and that becomes then the long pole on the 10th. then all patients after that, that would be patient number 75, patient number 100, patient number 125, those patients can be followed for the shorter time frame. And so we're really not, the most important part is we're not starting a 12-month follow-up clock at the last patient in. We're starting at 12-month clock substantially before. Now, of course, those patients that are being followed, after we lock the data set and submit our clinical module to the FDA, we'll still be following those patients. So in the end, the full study will follow all the patients to 12 months, but we don't have to submit on that. And that will give us an advantage in timing overall.
But all in, I mean, it seems like it's probably going to be 2028 before we see this approval. I mean, is that reasonable? Could it could it end up in 27, late 27? Is that possible?
I think so. There are three elements here. How rapidly can you enroll? How do we optimize that combination of six and 12-month follow-up timelines? And then how rapidly does the FDA conduct its review? If you look at the optimal outcome of those three timelines stacked or sequenced, you can get to the end of 27. And then as each one of those adds a little bit more time, you get to January 1st, you get to the first quarter of 28. But I think conservatively, Q128 would be our timeline. We're looking to have CE mark in the latter part of 2027 to initiate commercial potential prior to that. And importantly, of course, data will be flowing throughout. So we'll be moving from a clinical kind of phase to now regulatory phase, but I think with regulatory certainty based on the quality of evidence. So I think the overall tangibility of our story increases significantly throughout 27 with the penultimate approval from FDA at the end of that year or early in 28.
Okay. And then what's your approach with regard to mapping? Does mapping need to be used? And are you going to try to make it compatible with kind of the J&J Cardo and the Habit Insight Systems?
Yes. Yes. Mapping. Well, mapping, of course, varies depending on where you are in the world. But in the United States, we're a very mapping centric market and mapping, in my opinion, can absolutely enhance the quality of the catheter management and the lesion locations for the procedure. And I think most physicians feel that way. So improved mapping should make Pulse perform even better. And that's our philosophy. And as a result of that, we have, as we announced in our press release, we have commenced the IDE using the Abbott Insight mapping system. That is a, we call it a tight integration. So there's some proprietary software that is used in our, to render our catheter. And yet our system will be approvable for all commercially available mapping systems and can be used in the IDE with all commercially available mapping systems.
Okay. I think we're almost out of time, but I have one final question. So it was good to see that you're going to have a catheter where you can do kind of single shotting point by point. But what about RF capability? Because, you know, we've spoken to doctors, EPs, and it sounds like, you know, in some of the more complex cases, you know, they prefer to use PFA, but sometimes they still want to use RF for some lines or some ablation. So are you going to have any ability to have RF on your catheter as well?
We have no interest in developing a dual energy platform. We think that is a compromise as a result of limitations in first-generation PFA, and this is not something that we aspire to have. It is not necessary, in our view, with NSPFA.
All right. All right. Well, I think we're almost out of time, so thanks so much.
Thank you very much, Mike.
Your progress with the trials and commercialization.
Thank you.