Pulse Biosciences, Inc. ($PLSE)

Good afternoon, everyone. Good afternoon, everybody. I'm Paul LaViolette, Chief Executive Officer of Pulse Biosciences. Really proud to have this date in HRS. We've been trying to provide updates on every single critical meeting on the itinerary [indiscernible]. And today, it represents a really nice opportunity for us to see an normally got in. I just want to introduce a few of the Pulse members would not be [indiscernible] today. I'll be joined by Dr. David Kenigsberg, momentarily, our Chief Medical Officer, Chief Technical Officer, prospectively. I want to introduce Bob Duggan, our Chairman, our principal investor and really the visionary for the last decade behind the establishment of NSPA, as a next-generation energy to a play the EP and mining other parts of the body as you're aware.

And I referred -- and always.

Darren is our Whisper. I now want to introduce an you just keep there. She is Liane. Liane has just joined us as Chief Operating Officer. Liane has a pronounced career in Ventec, but impact 18 or so years in the EP space. Knows many of our clinicians knows the technology area in we're happy to have joined in to have some extra horsepower in the drive of our clinical regulatory and commercial are joining Jon Skinner, our Chief Financial Officer, the investor community couther. I think Jon, John well, build that is also here. Bill is the leader of our clinical and regulatory organization. And of course, as we enter this phase of driving the pivotal trial enrollment in the United States, Bill who has a lengthy career both that all can industry is a critical member. So thank you for joining. I'm going to turn to the floor over to Dr. Kenigsberg, most important estate. Company is like presenting these most important estate, company is like presenting these SP-6 Clinical volumes as from our feasibility study at the Symposium. Those data were very strong, they felt they were unprecedented. And I think there's a word that best describes to take away from today's presentation, it was that those results have been sustained. We've added additional patients out to 6 and 12 endpoints. And you've seen reinforcement of the evidence and outcomes of strength that we demonstrated in February to AFS. So with that, I'm going to turn it over to Dr. Kingsberg. He's got to walk through the data, give an additional perspective. Then Dr. Kenigsberg, Darren and I will answer your questions for the remainder of the session. Thanks.

Thank you very much. I'm David Kenigsberg, I'm a clinical cardiac electrophysiologist practicing in -- for LauderdaFlorida and I'm proud to be the CMO of this amazing company. I'm here today in the next 15 minutes or so to tell you why our technology at Pulse Biosciences is novel, unique and a game changer in electrophysiology and why I'm so enthusiastic to share the data and information I'm going to be sharing over the next little bit. I've been doing EP for 20 years, and I've seen every single energy source. We started out with point-by-point RF ablation. And at that time, I said, "Man, I sure wish there was a technology that you could just put in the vein, turn it on, isolate the vein safely, effectively and be done with it and have good long-term data." And we're there. That's what we're here to discuss today, and that's what I'm going to show you. I want you to all keep in mind that when I share the data, this is a very large, first-in-man data set. This is not a randomized trial. This is not even our IDE yet. This is first-in-man data. It's a heterogeneous, grouping of patients that were mapped with different mapping technologies. We kind of learned as we went while we did this. And even still the data is very robust and compelling. So this slide depicts what we have. So we have a very streamlined and easy to use ablation catheter where the energy is given between this inner ring and this outer ring and forms a toroidal ablation lesion in the pulmonary veins. In addition, there are sensors akin to a penta spine sensing catheter that can be used for mapping during the procedure as well as there's a magnet, which was recently introduced for magnet mapping procedures, which the end of our cohort we're able to benefit from. And this is where the magic happens, that's our console. And that console provides greater than 10,000 volts of energy, which if you look at any competitor currently FDA approved on the market, that's at least 5x or more what they can provide at maximum. So we have a very streamlined workflow. There's no need to rotate the catheter. The catheter goes into the vein. We provide an application in the vein. If you could look at the top, there's like this mushroom type appearance to the catheter, and that provides our ostial application. You could see it in this cartoon and in fluoroscopy. And then we pull the catheter back and position it at the antrum, each application is 5 seconds long and each vein gets 2 applications. There may be some additional applications, and I'll tell you about the average number as well as some early experience we have with the IDE. So the first in-human trial included 177 patients, 141 of which got a 5-second lesion and 36 got a 2.5 second lesion. We have landed at 5 second lesions because that's where our best effectiveness has been so far. And the study that we looked at was to try to assess the safety and efficacy of our catheter in a patient population that has atrial fibrillation. The study design was prospective. It was nonrandomized, single-arm feasibility study at 3 centers in Europe, the one in Hamaca that's very well known, a center in Belgium and Andrea Natalie's lab in Rome. Total number of operators were 7 operators. And this is the patient population. It's a 60-year-old on average patient population. The demographics are there. It's a fairly standard demographic for a first-in-man trial if you look at any of the trials that's done in the Afib space. And if you look at the procedure time and the success in this slide, it's extremely unique in the sense that, for the first time, if you give this catheter to an operator, they're able to off the bat, perform an effective procedure with amazing success. And that speaks to the form factor of the catheter and the streamlined workflow that we have by easily moving the catheter in the left atrium. It's very, very easy. This catheter does not require a lot of skill to position in, let's say, the right inferior pulmonary vein. So in the 5 second cohort, 141 patients, procedure time about an hour, L.A. dwell time about 18 minutes, fluoroscopy 9 minutes, although it could be done easily just with 3D mapping, especially now with our very integrated mapping with EnSight. 12 on average PV applications -- 12 applications to isolate all 4 pulmonary veins. So 2 per vein and then 1 on the carina, maybe 1 or 2 and tier to the right, that lands us at 12 applications on average to perform the entire procedure. And again, each application, 5 seconds. The acute PV success 100%. But if you look at the 6-month Holter data, 100%, 95 out of 95 patients, which -- with success and a 12-month, 96.2%, 51 out of 53 patients. That's amazing. Now if you look at the adverse events, we had a cardiac perforation tamponade ad really unrelated, in my opinion, to the procedure itself, but nonetheless happened to one of our patients during the first-in-man data. And then we had some homolysis resulting in some kidney injury. However, that patient's renal function fully resolved. If you look here at our 2.5 and our 5 second patient cohorts, and again, we landed at the 5 seconds. So I would focus on that. The freedom from any atrial arrhythmia at 1 year is 90%. So for first-in-man data, early experience with a catheter. This is an amazing Kaplan-Meier curve showing the excellent freedom from atrial arrhythmias at 1 year. Now if you look at -- this is very recent, our 5 second cohort followed out 12 months, 96.2% success rate by Holter and the 12 months, like I said, 90% freedom from any atrial arrhythmia. Now the difference between nanosecond PFA and microsecond PFA really needs to be elucidated and highlighted here. We're talking about 2 completely different things. We're talking about a catheter that can provide greater than 10,000 volts in a few nanoseconds versus a catheter that needs a lot more time and a lot less voltage. And the difference between nanosecond a microsecond at the cellular level is extremely important to point out. The difference is what we're trying to create with nanosecond PFA or what we're trying to create with ablation in general is clean apoptosis. We want to get into the cell and destroy the cell and not have any collateral damage. We want to have the absence of char or any other problems. With this technology, our nanosecond PFA gets into the cell and it kills the organs, kills the cell, kills the nucleus in a very clean and efficient manner, which differentiates from microsecond PFA, not only at the cellular level, but also, as you can see with our data for safety and efficacy as well as efficiency of the procedure. So this technology is unique. It's safe, it's durable. And as I demonstrated, has excellent clinical outcomes. We should definitely consider following these patients more closely. And I would mention that I predict in our IDE, it's likely because we have integrated mapping now that our data could get even better. And from -- again, my recollection from 20 years ago doing RF ablation where our maximum ceiling for efficacy was in the 60s. We're talking about 90% with early experience that could get better, that's spectacular. I just want to show you an example of 3D electron atomical mapping during the ablation with the catheter. This is with the Insight system. And as you can see, as we're applying in the vein, you can see where the electrical activity is on the bottom of the screen and then you could see that after a 5-second application, that electrical activity goes away and the vein is isolated. And then you move on from the ostial to the antral position, do the same thing and do that for all 4 veins. So did I skip a slide? No. So we just embarked on our IDE trial. And this trial is looking to enroll about 215 patients and up to 30 sites. The first patients were recently enrolled, and we're looking for some really excellent results to come, now that we have integrated mapping and we're bringing this trial to IDE. And the last thing I'll mention is Pulse Biosciences' nanosecond PFA is not a one-trick pony. This is a platform. This is an energy source that's novel and unique. And we have, in the works, focal catheter Epicenter plus, other things that we're working on that will add to our armamentarium to treat atrial fibrillation, not only the pulmonary veins, but other things like mitral annulus or CTI and so forth. Thank you very much for your time and attention.

Thank you, David. And I just want to mention that we are passing a microphone around the room and because we are webcasting this, if everyone could ask their question with the microphone, when the question is asked and as we're answering it, we'll move the microphone around to the next participant. And Darrin, if I could ask you to come on up and join. David, Darrin and I will now entertain your questions. Anthony?

[indiscernible] mentioned really the end of that for us to be 89% of stuff. So what happens time for procedure. And any key several times today of some postrenovation better demand to what you should if you had on hadn't think that's going to benefit or is.

Great. So Sorry. Fluoroscopy is definitely a mechanism to see the catheter and make sure that your catheter is in position with the vein either ostial or enterally. You could see the catheter conform to the osteal or antral position with fluoroscopy. And with PFA, as we all know, it's a contact sport. You need contact, but you don't need force, right? So it could be done with fluoroscopy. But in the United States, the majority of operators like myself are florals and we heavily rely on intracardiac echocardiography and 3 electronatomical mapping. Early on in our experience, the 3D mapping that we were using was pretty crude. And now we have very advanced integration with the 3D map. So I -- that's why I feel that with the IDE with integrated mapping, we could see better results. The time of the procedure is definitely going to go down. And I think you have to keep in mind in this trial, we did pre-maps, we did the procedure. We did complete post maps. Some of these patients received extrapulmonary vein applications. So I think the time will go down. I actually think in clinical practice, if you took this catheter today, again, this is a prediction. But if you took this catheter today to clinical practice, you'd probably see about a 30-minute procedure time around that.

On the data wanted to stay on perceive efficiency. I think early little bit has started just about the first senate enrolled patients in that set 1 day new operator to -- maybe just if you can give us more details some of these that you shared lease prior to the webcast helpful.

Yes. So we did 7 procedures that day before 5:30 p.m. in 2 labs with 2 teams and 1 operator. Procedure times were around 30 minutes. All procedures were done flurlessly with integrated insight as well as ICE and very efficient, and this operator never touched the catheter before. So I think 1 of the main differentiators about this catheter versus some of the other ones on the market currently is that this is very easy to use. You can hand it to someone and they'll figure it out. There's really no learning curve. I remember with with cryo, we had to do 30 cases to kind of figure out how to work it. It's not like this anymore.

Follow-up. [indiscernible] the system, I think there's plans to collaborate with other layers creation to their systems, any updates on progress sort the overall road map in terms of how many partners in terms of cost system face?

Yes. So our system, if you read the IDE, the IDE allows for any commercially approved EAM system to be paired with ours for the generation of data. That, of course, will lead to a commercial label that will allow for the same. So the way to think about this, of course, individual mapping systems can be open or closed, but the pairing with our system would be -- we would be considered open architecture to be used with any other system. As we stand here today, the EnSite system is likely to be the primary system to be used in the IDE enrollment. We don't have another custom integration available, but other systems could be used in a commercial setting in a lab in the next week or 2. We're emphasizing the Insight integration because we think that will deliver the best outcomes.

David, if you look at the enrollment time lines here and just kind of take typical enrollment follow-up time lines, let's assume the FDA does not cut in requirement at 6 months or follow-up on AM cases -- you're coming to the market in the middle of 2028. So the best words after you think about the unmet needs in the market at that point in time -- what does this technology saw and maybe you can talk about that from a clinical standpoint of maybe a site.

Yes. So the -- we can obviously massage the time lines, right, as a function of really the 3 phases. You've got the phase of enrollment, which we're working hard to accelerate and do as quickly as possible. You alluded, David, to the 6- and 12-month endpoints. We do have both 6 and a 12-month endpoint, and we'll use a blend of those and we can provide more details on that over time. And then, of course, the cleanliness of the data determine how rapidly you'll be reviewed at FDA toward the low end of that line at likely a 180-day review for PMA. So that lands us right at the beginning of 2028. Of course, it can go up or down from there. I think the beauty of the Class III medical device world is you can see what's coming. So we can predict with, I think, very high clarity, the likely lineup of products in 2027 and 2028. Of course, we know that things like Sphere 360 will be forthcoming something in the form of an omni pulse, not that much else. I would call it minor modifications to waveforms for perhaps a fairway Ultra, something like that. But I think that the lineup of fundamental systems will be the same that we see today. Those that are in later stage clinical development will be available in 2028. I would posit that everything Dr. Kenigsberg described will be needed in 2028. We will need improved workflow. If you think about the demand to drive patients through the lab, if you think about the desire and the economic value of doing 7 or 8 cases a day versus 3 or 4, those will be increasingly important pressure points in the delivery of health care in 2028. So if you take what we are seeing today in our European real world, yes, it's a feasibility study, but they're really doing it in a real-world setting with 5- to 7-minute ablation times, 30 minutes skin-to-skin procedure times. The potential has been alluded to by Dr. Reddy in his presentation for a sedation protocol in lieu of GA. Dr. Kenigsberg being a leader in the ASC movement in the United States. All of those trends are going to accelerate and the pressure will intensify based on the need to pull more patients in and their desire to be treated frontline therapy with ablation instead of drug. So what I think you'll see between now and then is a market that has procedure volume that's probably 40% greater, only 2 years from now than today. The emphasis on workflow efficiency greater than today. And if you think about what's the greatest inefficiency in health care delivery overall, it's the treatment of that same patient a second time around. And so as our European feasibility data roll forward, we increase the N. We increased the follow-up. It becomes clear that our -- the top possibility for superior outcomes exists. The reduction in second treatments on a per patient basis. That's a boon for the health care system and for everyone trying to deliver efficient care.

At the season. We saw more early on competitive systems results for recent 100 toll applications that a 1x 2.5 hours. That deal senator efficiency can be more impactful than tar. So you see a little bit about the characteristics of demanding the PT setting. And also, there is a trend toward Dose available Darrin, just the also current.

Yes. Those are really good questions. So on the nanosecond side, the thing we do, I think we know is nanosecond is very different than microsecond. One of the ways it's very different is that these nanosecond pulses penetrate tissue deeper and more homogeneously, right? So we operate below the charge time constant of cells, which allows us to pass through the cells. By passing through the cells, we get deeper and we're more homogeneous. This is important in the atrium for sure. It will definitely be important in the ventricle where you're treating more tissue and you're working through scar and other things like that. In the HRS meeting this week, we had a poster that was presented by Mount Sinai on a focal catheter kind of an early-stage focal catheter that we developed. That data looks very promising. It's ablation depths in the 10 millimeters even at sort of modest energy levels. So we think this technology is going to be able to deliver very deep lesions all over the heart and very efficiently. So we can definitely move very quickly. David showed you a second-generation design, which combines a focal catheter with the current epicenter catheter, allowing you to do sort of circumferential ablations, but also lines and spots and those kinds of things. That also really drives efficiency of procedures, especially when you're doing things outside of the pulmonary veins. So in those cases, you're doing veins, posterior wall plus spots and lines and whatever else you need. And so we haven't participated in the ventricle as of yet, except for in preclinical work. But I think the opportunity is there, and I think this is a technology that's going to work quite well in that chamber of the heart. Yes, sorry. So the dual energy side, as an engineer, I'm going to walk out on the limb and say, I'm not convinced that that's necessary. I think it depends largely on the application. There's some data that suggests PF before RF or RF before PF and the same lesion can be a little bit bigger. We haven't seen that in our hands. And I think maybe that is more an indication of microsecond PFA needing to get deeper as opposed to a nanosecond, but we'll see. I mean if other energies can be brought to bear and create a more efficient workflow, we can certainly do that. It's not a -- these are, I think, engineering activities that are doable and not a long time horizon. But I think the first step is do we really need that. That adds a lot of complexity, obviously. I think a single energy with devices that are designed for that energy source that can deliver the kind of lesions you need is really the optimal solution, and I think we'll drive for that before anything else.

Canaccord. Congratulations of data presented today. And my question is really about efficacy and some of the commentary and the follow-up. It was provided this was -- and I'm curious how you think about these variables, the patients weren't sick. And now we're talking about a pivotal trial like we're doing them faster. We have to have to keep abilities, but they're not. How you think about this as you run the trial, they're doing it faster, they may not get higher efficacy versus what's more important is speed is it efficacy? And I'm just trying to kind of think about you how much did the product change on the iterations? And why did you see coming out [indiscernible] confidence that we could see kind of better outcomes is.

Yes, great question. So -- as I said, we kind of learned as we went during the first in man. And some things we learned were how many -- how long should the lesion be, 2.5 seconds or 5 second applications? We settled on 5 seconds. So that right there, we showed that, that data of the cohort is better. Mapping integration. We went from really crude mapping integration to fully integrated. As far as the post presentation commentary by, Proch, I think it's great. I think it arms us and invigorates us to show everyone that we're going to provide the best possible data through our IDE now that we have figured out the time, integration. And as far as patient population, this is all commerce. These are patients that we had. I guarantee the U.S. data, the U.S. population is different. Usually in Europe, we have healthier patients that are studied in the U.S. Unfortunately, we have sicker patients, and that will show through probably. We're not cherry picking the patients. These are patients that are enrolled in the IDE, they're all comers.

Yes. I would just make one comment also. I think we can't overemphasize the benefit of a really tight integrated mapping system. You saw it in the videos that we showed and maybe you didn't pick up all the nuances. But as they ablate, you see the color change, you see this kind of blue area, like that's where they've ablated, so they know now that they can move on. They know that they're filling in all of the areas. And that was sort of available in different iterations of it through feasibility, but largely maybe only over the last several months, has it really been at that level with the magnetic sensor in the catheter. So that speeds up the procedure for sure. I mean, anecdotally, I mean, a lot of procedures these days, they're in the 30-minute range, almost all the time. And it will improve outcomes because they can see better where they're at. and they can treat things. I mean it's a little bit, honestly, if you were driving a car at night and you were holding a flashlight out of your window to try to see where you're going, that's how it was before we had good integrated mapping. Now we have headlights. So it's phenomenally better. I think we don't even -- we don't see it in the data because it hasn't been in there long enough for us to see it. So that's, I think, why we're so optimistic. And you can see it. When you watch these cases, it's obvious. If you talk to EPs, I mean, if you talk to anybody, they'll be able to articulate it, like David.

I listened to your commentary, just really so technology that very well selling. Curiously, you hear the doctors use is your general.

Yes. So I've done about 40 ablations in an ASC setting. And the most important thing about an ASC setting is the doctor who's doing the procedure is basically on an island. And there are no other doctors that can bell you out. There's no CT surgery. You need a procedure that's safe, that's effective and that's efficient. This fits all 3 of those criteria. This would be an ideal tool for an ASC setting. Unfortunately, for me, it's not available yet.

You mentioned learned Were there any changes in the procedural strategy that they are really going to show up in terms of beyond that in terms of workflows for the larger assets?

Yes. I mean as you do a procedure, there are many things that you kind of think about. I'll give you an example and I probably won't be able to list all of them off the top of my head, but I'll give you a quick and easy example. The sheath. So at the beginning, we were using one sheath. And at the end, we've landed on a sheet that we feel is just generally safe. It really has nothing to do with our catheter, but we feel that, that adds to the safety of the procedure. One thing to think about, I mean, I know it may be obvious to all of us in the room, but there are many things outside of the catheter that's being studied that can go wrong in a procedure, and we need to control for those things. Patient selection, are you irrigating through the sheath, are you getting the right ACTs, anesthesia-related things, groin-related things, pericardial fusions that aren't totally unrelated to the procedure. So yes, as you go through a first in man, you kind of think about all these things. But yes, I think that those are the reasons why we do IDEs and other trials.

Just on [indiscernible] going to be in or -- so it sounds to get front of Cardona some point is there a margin curve to match and it falls from cargo and I guess we also study. Just how Mascoma how.

I can answer in a slightly different way as a clinician. We're only going to allow mapping in that's tightly integrated to the point that it's right now with EnSite. So we actually do have an iteration with Cardo, but I don't like it enough to say that it's as tightly integrated as our EnSite is. If they can get there, we're happy to use it. It's up to them.

In this study, generally, how important to maintain [indiscernible] will be feasible in the ASC at scale is moving at conscious state? And the [indiscernible] so sales interaction to rebut.

So anecdotally, I happen to be in some of these cases in Prague and I know of a handful of cases where the patient was pretty much awake and there was really no extra cardiac stimulation. So yes, it could be done. And yes, it could be done under conscious sedation/deep sedation, which is basically Versa and pentanol plus a little propofol at convenient times during the procedure to keep the patient comfortable, which is what we currently do in an ASC. So I think as far as anesthesia goes, this catheter and technology lends itself to an ASC setting for that reason as well.

[indiscernible] partnership, what other strategics? Has anything changed just a savintegration with Ensite. Is that the partnership, competing about kind of the strategy.

Yes. Great question. Number one, the strategy has not changed. And number two, the short-term integration steps that you see, they're not indicative of a larger partnership and maybe Bob Duggan can answer as well.

Even senior to that, I've invested in a number of very successful companies. One of the keys to that is that are you invest in source if you're investing in licensor that when they need to pay a change that are back the source, they go locate the source. RT is a source that our competitors response -- so it comes to doing something different. They've got to go back to the book they were at or better creator. We don't have that data. We feel it's great procedure, straight in the the Ks and the source of creating bolstered the last 2 years. So that's why we hear a particle. So and we'll do what's necessary. So we're now presenting procedures to best than 200 patients compared to 10,000 and 15,000 sets a fill our competitors. So was asking robotics. Bob, you've been in probation you're no better than Humana as it follows even an vendor, 400,000 -- excuse me 5 more years noble ever procedure is we have over half the procedures of our box. Now is the spot for in and spare we're the source of have some great confidence that we're going to go push future is incredibly bright, want solitaire you get too far out front and you may invert iatrogeninstances that and never should happen, but it did happen it makes the headlines -- so we're fluid in a really nice space in many life of 8% [indiscernible]. She's the Chief Operating Officer, vector ease the mic. Some of you may know her. I didn't know it too well, but I want to lower the stores that I bet, but just a few why you're within.

Sure. So yes, it's not that long ago, but a really long time to small made is I say you better call and the [indiscernible] acquisition. So they were about 20 years lecturing and physiology and tiering. So a lot of engineering that ground. We go to the clinical and business side of the [indiscernible] there, right, a large portion of a vision creates on the market sales bringing all the can only mark would say has sort of been that combines really to these folks. This technology is extremely exciting and very differentiated and will be to [indiscernible] talked to plan.

So it's a little [indiscernible] that plays into the full growth.

Yes. I mean, I think it's it reads directly on it. This is an energy that can be used to lead tissue very effectively. And I think our clamp is a really exciting implementation of a device that utilizes down a second PFA. Similarly in that it is very, very efficient and effective at ablating cardiac tissue. So cardiac surgeons use the clamp in concomitant procedures. They do a handful of ablations. It typically takes several minutes. And they can fully complete the ablations that they need to do to treat that AF and then they move on to replacing the valve or whatever. But it's -- certainly, on the cardiac side, you can infer from this data that you're getting very good ablations that will translate directly to our clamp.

Any last questions? Okay. Thank you so much for joining. Bob, do you want to...

[indiscernible]

Great. Thank you all. It's a pleasure to have you here.