Good afternoon, everyone. Welcome to day three of our 43rd Healthcare Conference. My name is Mary Liu, and I'm an Associate in the Investment Banking team at J.P. Morgan, and it's my pleasure to introduce our next presenter, Pulse Biosciences, and joining us today, the company's CEO and Co-Chairman, Paul LaViolette, and we will have about 10 minutes for Q&A after the presentation, and without further ado, I will turn it over to Paul for the presentation.
Thank you, Mary. I appreciate that. And it's great to join you all. As Mary mentioned, I'm Paul LaViolette. I'm the newly appointed Chief Executive Officer for Pulse. I have been in the medical device space for 45 years. Over that time, I've participated in dozens of markets and a lot of exciting technologies. I tend to focus on great technologies, disruptive therapies, and very large market opportunities. And suffice it to say, through that lens, Pulse Biosciences becomes an extremely compelling opportunity and one that I could not refuse to participate in. I've joined the board over the past year, and I'm extremely excited to enter as the leader of the team. We will be making forward-looking statements today, so here is our disclaimer in that regard. Let me just spend a second on the mission of the company. This mission focuses exclusively on nanosecond pulsed field ablation.
We'll spend time talking about both the importance of PFA and the differentiating element of nanosecond pulse durations in comparison to what everyone is now seeing but may not appreciate the distinction of, which is microsecond pulses, primarily today being commercialized in electrophysiology. Our intent is to build a thriving company, a viable entity. We're not trying to build a small company and be acquired. We're trying to build a platform that ultimately has the reach to treat as many patients as possible in multiple clinical sectors. We're seeing clinical evidence today emerge in three different categories. We've conducted hundreds of preclinical studies. And while we'll talk today about three new opportunity markets, we will have many more to follow hereafter. I just want to, I guess, reinforce the message with a quote from Dr. Niv Ad. Dr.
Ad is one of the most published and prominent cardiothoracic surgeons in the world. He happens to have joined Pulse as a Chief Medical Officer, giving up 50% of his practice time to work with us. Reflecting on his first exposure to preclinical and clinical results, he effectively described this as an energy that will replace all other energies and as a therapy that can ultimately expand markets that it enters. Now, obviously, he was referring mostly to cardiac surgery, but I would say that characterization is applicable to every market that we're looking at. And we'll spend a little bit of time describing precisely how that will work in the areas that we're focused on. A couple of snapshot items on the company in regards to the balance sheet and the management team, and then we'll dive into the technology.
This is a company that has a very strong balance sheet. We're not raising capital now. At the end of December, we had $118 million cash on hand, pro forma $130 million, and no debt. That provides us a multi-year runway. Based on 2024 investment activity, we had $36 million of runway expenses. We expect those numbers to increase in 2025, based both on commercialization investments in our first go-to-market strategy for thyroid treatment, as well as multiple IDEs that we will commence throughout the course of the year. And we'll give you some perspective on those. We have very strong insider support. The company has been supported aggressively with investment capital. We'll describe some of that in a bit. But this is a very strong story, a very unique structure, a strong balance sheet, and a great mission. And we're really excited to be pursuing that aggressively.
The management team that I'm joining is extremely experienced. We have multiple executives with CEO and C-suite experience led by Darrin Uecker and Kevin Danahy as the CTO and the CCO, respectively. As I mentioned, I've been doing this for a while. I have 30 years of operating experience, perhaps known by some to have been a leader at Boston Scientific for 15 years, an investor for the last 15 years. I've been on a few dozen medtech boards, had a few dozen medtech exits. I know and have participated in probably 35 or 40 different medtech markets. So we have a tremendous amount of experience now in this business, and that is fitting for the opportunity that we're pursuing. I mentioned Dr. Ad.
We have multiple chief medical officers, and I highlight this solely to reinforce the conviction we have about bringing deep medical and clinical expertise to our team early on as we explore and pursue multiple markets. We have an extremely skilled and engaged board of directors. This team has been together working on multiple companies, anchored by Bob Duggan. Bob is a legendary investor and serial entrepreneur, has many successes to his name, and this team is really leaning into creating a great success story here at Pulse Biosciences. Let me spend now a few minutes talking about the technology platform. I want to really emphasize a minute difference.
And when we think about PFA today in the marketplace, some of the successes that you're familiar with in medtech, some of the biggest stories actually today in medtech, they relate to pulsed field ablation in a category that is defined by microsecond pulses. And microseconds would be defined as one millionth of a second segments. And so when you think about delivering PFA pulses into the body, those pulses will start and end over the course of some number of millions of a second. And that sounds rapid. I think what's really important to understand, while we will benefit from the attributes that are generic to PFA, Nano-Pulse or Pulse Biosciences is delivering Nano-Pulses. And those are seconds that are divided into billionths segments. So if you think about that, it sounds shorter, but it's imperative to understand that a billionth is a thousandfold different than a millionth.
And so this is not a small distinction in technology. And while it may be imperceptible to us in practical engineering terms and in clinical outcomes, that difference provides us a great technology advantage and great outcomes advantages, which we'll begin to describe. We have all of this engineered into a console that captures all of the energy parameters that are then software tunable, so we can use the same console for multiple applications of those nanosecond pulses. Unlike other companies that tend to use generic, which is to say non-protected microsecond PFA, they tend to start with that as a generator, take RF applicators, and apply nanosecond pulse or microsecond pulses through RF tools. We have started with entirely clean sheets of paper designed tools expressly for the purpose of delivering Nano-Pulse energy into the body.
As a result, we have a number of design advantages, which we'll describe in a little bit more detail. The company has been extremely assertive in developing intellectual property. We have 103 issued patents, another 100 pending, substantial investment in research and development beyond that. This is really a fortress of IP and of technology. If one scans the market in search of another company practicing nanosecond PFA, you will not find one. We have been developing this technology for some time, but it is now at the precipice of clinical and commercial launch. We're starting our first launch in Q2 of 2025. We're also commencing three IDE studies in 2025. This is now a time when we turn the corner. The company is entering a different, later, and more mature stage.
We're extremely excited about the prospect of bringing these technologies now into the clinic and into the commercial marketplace. If you think about our opportunities on a U.S. addressable basis today, we're targeting three categories that offer us $6 billion worth of addressable markets. That's based on our first-to-market indication for benign thyroid nodules, which I'll describe in more detail, followed thereafter by a cardiac surgery application, which is an existing market, and of course, the EP ablation market. Both of those last two are for atrial fibrillation, which of course is the single most common cardiac arrhythmia in man. Those add up to $3 billion today in the United States. If we think about those over time and on a global basis, the first three opportunities for Pulse Biosciences amount to $16 billion of addressable opportunities.
So we're very blessed to have substantial market opportunities where nanosecond PFA can really make a dramatic market and clinical difference. We have a strategy that will move into new categories such as thyroid. Thyroid, admittedly, is not a market that medtech veterans are used to hearing about. And we'll identify additional greenfield opportunities along with the entry into significant existing markets. So in short, if you think about PFA and what it does, it's entering the energy fields. We know that millions and millions of ablation procedures are performed across multiple medical specialties and chronic conditions. They typically use extreme temperature, either in hot or cold, to destroy tissues, to create aggressive tissue necrosis. The good news is that has enabled many procedures to be converted from open surgery to less invasive alternatives. But those energies destroy tissue. They incite inflammatory responses. They leave behind scars, and they're suboptimal.
We're watching today, with the conversion of the EP ablation market, a paradigm shift where PFA is rapidly converting existing radiofrequency or cryoablation applications, and that is because PFA is substantially faster. That speed, of course, enables a conversion of more procedures or performance of more procedures per day and some additional safety, and in the example of cardiac ablation, the creation of esophageal fistulas, of course, would be one of the top adverse events that physicians are concerned about, and so PFA has built a reputation for avoiding that type of event, and that sort of safety benefit, speed benefit drives very almost unprecedented market conversion. With that in mind, it begs the question whether PFA, as well as it is performing, leaves gaps for next-generation technologies to fulfill.
I would like to just emphasize with maybe a head-to-head comparison exactly how that will be done and the magnitude of the opportunity that nanosecond PFA will fulfill. Here's a listing of some characteristics and how we might think about microsecond PFA performing. If you think about this in the specific EP application that the market is exposed to today, you see that several catheters are required. In an individual application of energy, let's say within EP to treat AFib, one would go after ablation of each of the four pulmonary veins. That's a very standard procedure. To ablate a pulmonary vein with conventional PFA, one has to deliver energy about eight different times. Each time, there's an overlapping process, a rotation of the catheter, and that catheter is laying down individual points of ablation.
And the goal of multiple energy deliveries is to try to overlap those points of ablation to the degree that a full regional isolation has occurred, leaving no gaps for aberrant arrhythmias. In addition to that, in addition to all that work, right, all of those ablation deliveries, it takes about 30 minutes in total to complete that time. And each lesion is about 4-6 millimeters in depth. Now, because those pulses of energy are residing in the body for multiple millionths of seconds, those energy waves are picked up by nerves. And nerves respond to energy with muscle spasm. And as a result, those patients have to be significantly anesthetized so that they don't move on the table. So that's the state of micro PFA. If we then move into the exclusive realm of nanosecond PFA of Pulse Biosciences, you see a dramatic difference.
Instead of needing multiple configurations, you only need one catheter configuration. Instead of delivering eight applications of energy to isolate a pulmonary vein, you would generally only need to deliver one application of energy. As a result of a single delivery of energy, you don't need to manipulate the catheter. That's going to significantly reduce the operative or the ablation time of that procedure, and if you think about reduction in manipulations, reduction in time, it's about a 50%-75% reduction in both, so when we think about whether there remain significant clinical and time gaps in the performance of PFA ablations today versus what nanosecond PFA ablation would deliver, you can see there is meaningful opportunity available.
And if you think about the rapidity with which the market is converting today and look at the magnitude of benefit that nanosecond PFA can provide over PFA today, one would believe that that same degree of improvement is available on a go-forward basis. So we think we're in possession of an extremely novel and clinically meaningful energy with multiple applications. If we just dive in a little bit more to how that nanosecond PFA differs from microsecond, just look at these two graphics. On the left, microsecond PFA is intended here to be drawn out, right, because it's 1,000 times longer than nanosecond. And because it's much longer, it's kept at a lower amplitude of energy delivery. However, the area under the curve is still relatively large.
In comparison to on the right, where you see a much briefer pulse duration, allowing a much higher amplitude of energy, much more voltage to be delivered in a much shorter time, but still keeping the total energy delivered into the body at a much lower total amount, and that creates significant advantages for us. The higher amplitude creates deeper lesions. The shorter duration avoids nerve capture, allows entirely different and more flexible tools to be used because we don't have to deliver as much total energy through our catheters. It's really a revolutionary step in PFA, even though current PFA is performing quite well, so in aggregate, the advantages of nanosecond PFA are numerous. We get to explicitly design devices to connect to a single generator. Those devices are purpose-built for PFA.
Without the engineering burden, if you will, of microsecond pulses, we lower the total amount of energy, which lowers the burden on the patient. We reduce the capture of nerves, which means procedures can be performed with lower anesthesia levels. We do not create any heat footprint. There is no thermal uptake. There's no heating of the zone where our ablation is taking place. It really performs a significantly different procedure. I want to now spend a minute moving through this and onto our focus on our business model. With all of these applications, with all of these benefits, can we attack multiple markets ourselves? The answer is that's not our plan. Our plan is to identify markets that are addressable, that don't have significant competition, where we can enter and where we can dislocate patients from surgery into minimally invasive procedures such as thyroid.
We'll build those markets ourselves. In other markets, perhaps EP, where markets are larger, systems are more complicated, hurdles to entry are larger and would require significantly more capital to move them, we would consider a partnering relationship, so over time, Pulse Biosciences will build a combination of direct and partnership revenue streams, attacking as many markets as our energy can ultimately pursue, and with that, I want to start by talking about our first indication, which is benign thyroid nodules. Now, the thyroid is a gland that produces hormones that control significant bodily functions, including body temperature, heart rate, blood pressure, metabolism. One would want to preserve one's thyroid if you could, and it's particularly punitive to have to undergo removal of a thyroid for a benign indication, but benign thyroid nodules are the number one most commonly diagnosed benign thyroid problem.
That leads to 250,000 diagnoses per year, which converts to 150,000 thyroidectomies and 100,000 patients moving into a watchful waiting category where they simply refuse to undergo surgery. We are looking at a therapy that uses percutaneous ultrasound-guided percutaneous treatment of the thyroid, avoids surgery, leaves the thyroid function entirely intact, eliminates symptoms, reduces the volume of the growth, and restores that patient back to normalcy. If you think about converting the thyroidectomy volume to percutaneous and then pulling patients refusing surgery from watchful waiting into this minimally invasive approach, you can readily build a market of multiple hundred thousands of procedures per year that Pulse Biosciences would own exclusively. We think that can build to a very significant billion-dollar market opportunity that we alone would have access to.
So it's a new paradigm both for the surgical population today as well as for the prevalence pool that exists in the current market. Here's an example of a patient that has been treated with nsPFA. You see a significant growth in the image on the left that is completely resolved at a follow-up period. And that patient has had no surgery, has no scar, has complete thyroid functionality, and is, in the end, restored to a baseline performance as if the benign nodules had not been there to begin with. So we're extremely enthusiastic about this opportunity. If you think about where this goes, this is an FDA-approved platform. We're completing a confirmatory clinical study in the United States right now. We have 10 centers participating in that.
At the end of enrollment, which will be just next month, we'll begin to convert those centers into our first commercial sites. And this is a field that will go commercial starting in Q2, expanding throughout the second half of this year. And in parallel, we'll run an additional post-market confirmatory trial to gain a de novo indication specifically for thyroid. So this is commercial in 2025 with concurrent clinical evidence generation. The second market is cardiac surgery. This is an existing market that we intend to enter and have the potential to substantially expand. Cardiac ablation is performed on patients who are undergoing open-heart surgery, who enter the operating arena with pre-existing diagnosed atrial fibrillation. Knowing you have AFib and having the heart exposed, one would think you would treat that patient for AFib all of the time. That is not currently done.
What is currently done is the application of RF energy through a clamp that produces a delineation or an ablation line along preset guidelines that should deliver AFib-free results, but is generally burdensome to do, not fully effective, and sufficiently unreliable such that it is only done about one-third of the time. So you can think about 300,000 surgeries a year, about 80,000 of whom should be ablated prospectively on the table. Only about a third of those, only about 25,000 procedures are done. So as we enter this market, we believe we can convert the RF business over to nanosecond PFA. We believe we can very shortly thereafter capture additional interest in the patient population because those patients are on the table and we would be delivering a more effective therapy.
And then we have the potential to treat an additional group of patients who are on that table, who are at risk of acquiring AFib as a result of the procedure, and who will have newly acquired postoperative AFib within a week following their discharge from the hospital. This creates a different patient procedure opportunity for us where it takes 25,000. We think we can do that by offering a tool that is essentially the exact same in the hands of the surgeon as is available today that delivers radiofrequency ablation. That radiofrequency ablation is delivered through about four or five ablations per line, each of which lasts 30 seconds. The Pulse Biosciences nanosecond delivery is one ablation of two seconds. I think you'd find that compelling. We're running a clinical study today to build this out. We will enter an IDE in the middle of this year.
This has been designated as a breakthrough therapy by FDA in the TAP program, which I think speaks very highly to the fact that this is a compelling technology. The last one, and then we'll finish up, is the EP market. You need little introduction to this market. It's closely followed. It's extremely large, multi-billion today. It's undergoing a transformation with PFA, but as I mentioned earlier, there are still significant gaps in how microsecond or current PFA treats those patients. And we believe nanosecond PFA will deliver dramatically different results, and we are seeing clinical data today to demonstrate that, so this is a market that we would enter. We don't need to build this market. We don't need to expand this market. We need to introduce nsPFA for the purpose of converting this market.
If you think about our technology delivery, I mentioned earlier to you that the current approach is to treat with a catheter, rotate, treat again, treat again, treat again. If you look at this image of the catheter in the upper circle, you see a zone of ablation that is circular, contiguous, and covers the entire target with a single circumferential lesion. This is unprecedented in today's approach because current microsecond PFA delivery systems cannot deliver enough energy to ablate a zone of this size. We think this is highly differentiated, and I'll give you a closing comment about how this will change EP practice based on the EP or based on the clinical results that we see so far. The status for this program, we're moving it through a clinical trial today.
We will actually present the results of that clinical trial at the AFib Symposium in Boston on Friday of this week. And we will follow up with a live telecast of a case of how this technology works on Saturday morning. So this is in the clinic. We're expanding sites from the first site in Europe to three total. We're expanding clinical data accumulation. And this program will also move to an IDE in the middle of this year. In summary, when you look at Pulse Biosciences, you see a company that has command of a novel energy. We know that PFA is doing well in some categories today. That's an understatement. We believe that we have command in the form of a proprietary, extremely distinct form of PFA. And we are intent on bringing that into multiple markets.
We have an extraordinary IP estate, 180 issued patents, many more to follow. We have built years of preclinical science and are adding to that now a series of clinical studies. And each one, frankly, is better than the next in terms of quality of outcomes and disruptive potential. We're validating that with three IDEs that will start in 2025. The markets that we're going after today provide us at least $6 billion of U.S. addressable opportunity, two and a half times that on a global basis. We're going after multiple indications in soft tissue ablation, cardiac, and others. We're becoming a commercial platform literally in the matter of a few months. We have a balance sheet that will fund the company's operations and all of the milestones that I just described over the next couple of years. So we feel we're in a very fortunate position.
With that, I'll just stop with this one image. When you think about EP and becoming an ablator, the learning curve using radiofrequency ablation to perform point-to-point therapy in pulmonary vein isolation, that learning curve is about 150 cases. We performed all of our cases in Europe in a single site. As we expanded from the first site to the second site, this is an image of a physician in Brussels who performed his first case with no learning curve, no prior cases, no preclinical exposure to this technology. You see perfectly isolated veins on that image on the right-hand side. All of that red area is completely electrically isolated, exactly as one would want. This case was done first case ever with 10 minutes of ablation time. I will tell you that is exceptionally disruptive to the electrophysiology market.
And with that, I'll close my comments and look forward to answering any questions you might have.
Great. We can pass around the mic if anyone has questions. And I can probably kick off. Could you maybe talk a little bit more about how the mechanism of action differs for the nanosecond versus the current microsecond?
Yes. And that is, I'll say, it's deeper science, which I didn't delve into in the prepared commentary. But what really matters here is that microsecond pulses create what's generally described as irreversible electroporation. They create holes in cell membranes. And that's what generates the value of PFA as we know it today, conventional PFA. Nanosecond PFA produces, because of the very short burst of energy, that very compressed amount of time, we are able to deliver higher amplitude energy into the body.
That energy is capable of penetrating not just into the cell membrane, but into the nucleus of the cell itself and into the membranes of elements of the cell, such as mitochondria. That allows the cell to begin to destruct, if you will, without signaling to the body that an abnormal necrotic process is taking place. The cell enters regulated normal cell death, and the body is used to that and therefore doesn't really generate an organized response. That means there's no inflammatory response, there's no scarring, and the mechanism for nanosecond PFA is fundamentally distinct from the mechanism of microsecond PFA. I think it's a really important distinction.
Great. Thank you.
Bob, do you want to address the market and sales build-up as we're going through?
Sure. Thank you, Bob. We are going commercial, as was mentioned.
And in our first application of commercialization, we'll be going after the thyroid market. The thyroid market is actually quite large, as I mentioned, 150,000 current thyroidectomies. And those are concentrated in roughly 200 major centers, although about 1,100 total centers are active in thyroid surgery with endocrine surgery practices. As a result of an absence of competition, as the result of an absence of technologies that we would need to displace, we really have a no-resistance launch. And so that allows us to go from the 10 sites that we have today in the clinic that will be converted to commercial. We'll roughly double that between Q1 and Q2 and double that again between Q2 and Q4 so that by the end of the year, we expect to be in between 40 and 50 sites of the highest volume of endocrine therapy.
And if you think about accessing that group of accounts, we are building a relatively small team of two types of direct selling resources. The first that would be in place to get the capital equipment into the hospital, a relatively arduous but predictable process. We'll have a couple of folks doing that. And then we'll start with about a half a dozen therapy development specialists or territory managers that will sell directly to endocrine surgeons to bring this therapy to their practice. I will tell you within the clinical practice that we have now, we have 10 KOLs involved in our work.
The incoming demand from their peers that are the leaders in the American Thyroid Association is very high, and we expect that we'll be able to roll this out very efficiently, place capital by selling it, not by placing it free of charge, but we will sell capital, place it into accounts. We're currently working on the final procedure training program, and we'll refine that over the course of the next few months, and then we'll literally go live commercially in Q2 and expand that consistently throughout the course of 2025. By getting to those 50, we're going to about a quarter of the immediately addressable market. And the addressable market, most importantly, is defined by high-volume thyroid accounts that have a high volume of surgical practice, and they also already have ultrasound guidance skills, so they already know how to do percutaneous procedures in the thyroid.
You can then layer nsPFA into their hands, and they have a relatively low hurdle to initiate patient treatments. Can we touch on the capital equipment selling price as well as the end-effector recurring revenue? Yes. The capital that you saw there, a single console that contains the nanosecond pulse field generator and all of the software to manage the algorithms and deliver the energy, we're targeting that at about $100,000, which is well within most capital acquisition processes. We think the value of our procedure in comparison, let's say, to approximately a $20,000-$25,000 thyroidectomy charge, that we will be very comfortable in placing a $4,000-$6,000 average selling price range on the single-use device. You think about 175,000 thyroidectomies.
You think about penetrating into that with a very disruptive new paradigm-shifting therapy and the prospect of approximately $5,000 selling price per case.
Paul, in the thyroidectomy, I believe it requires permanent medication post-procedure. Anything such as that with the approach that you're discussing today?
The answer is no. So for those who couldn't hear the question, with a thyroidectomy, with the reduction of that hormone access and the loss of hormone control of those bodily functions that I mentioned, those hormones have to be replaced. So anyone undergoing thyroidectomy has significant medication burden. Anyone on the watchful waiting list has to continuously be monitored for that same set of hormone balance, if you will, by endocrinologists. So the goal here is to eliminate the volume of the benign nodule while preserving thyroid function entirely and restoring those patients to normal lifestyle on a drug-free basis.
So one would think those that are under medication and on a recurring basis visiting the endocrinologist will, in time, locate this procedure and be converted to it. They're not people that can't be found. Exactly. It's a really important point. When you think about a watchful waiting list and you think about other markets, I'll just make one up as an example. You think about renal denervation for hypertension. It's wonderful. You can get patients off medication. You can lower them down to a normotensive level or closer to it. But those patients are out there. They're diffusely dispersed in the marketplace. They're not actively being managed. When you think about patients with benign thyroid nodules, they are actively being managed within the endocrinology practice.
The arrival of a breakthrough therapy like this, it's very easy to take a patient who is undergoing an evaluation today, diagnosed today, being referred to surgery today to disrupt that pathway and move that patient from surgery to a less invasive alternative. If you have two million patients in watchful waiting, how do you activate that patient population? Because those patients are actively managed by endocrinology and routinely involved or engaged in the healthcare system coming into the physician's office twice a year, when a technology like this becomes available, it does not take much energy to activate that patient to become interested in a breakthrough therapy like this.
So we think we'll have a very active draw of patients undergoing thyroidectomy and a very active draw of patients in the prevalence pool who want to get off watchful waiting, off medication management, off of the symptoms associated with their enlarged thyroid and into a minimally invasive alternative for the first time available to them ever. We have one minute left. Any last question?
Do you have any brothers or cousins that are experiencing challenges?
Well, I'm a twin. So there you go. Thank you very much.
Thanks, everyone.