Thank you, Rohin. Thank you to J.P. Morgan and to all of you for joining us this afternoon, both here in the room and online. I'm excited to have the opportunity to talk with you about an update on NeuroPace and both our recent results as well as our future focus, so with that, I'll jump right in, so our forward-looking statement and disclaimer slide here to be noted, and I wanted to start in particular with the mission of the business, and I wanted to do that because it really does give you a feeling for who we are and what we do, and what we're focused on is transforming the lives of patients suffering from epilepsy, and that catalyzes our decision-making and our focus.
And if you were with us in our Mountain View offices, you can feel the sense of stewardship and responsibility that we all have toward providing innovative technology and treatment for patients who need it, who are resistant to drugs in terms of controlling their seizures in drug-resistant epilepsy. So, the rest of my presentation is going to talk about who we are and what we do in pursuit of this mission. And this is a quick snapshot of us from an investment highlights perspective, but also kind of from a foundational and fundamental elements perspective. Drug-resistant epilepsy is a large, largely unmet need.
I'll talk a little bit about the treatment gap in the market here in a moment, but more than a $2 billion annual market opportunity within our current patient and customer indications, and additional TAM up to north of a $50 billion opportunity when we think about the broad unmet need with patients here in the U.S. alone. We address that unmet need with a unique technology. The unique technology is the RNS System. It's a closed-loop neuromodulation system consisting of a pulse generator and two leads. That is the first and only closed-loop approach to being able to monitor, sense, record, and deliver therapy for this patient population. And I'll get into the technology a little bit more here in a moment as well. From a clinical, the unique nature of the technology really shows up in the clinical evidence.
The clinical evidence has shown differentiated outcomes, not just differentiated outcomes versus other approaches, but outcomes that improve over time. We've got a real bevy of clinical data both under our belts as well as underway. I look forward to talking with you about those emerging indications as well as some of the work that we're doing for our currently indicated patient populations as well. While we're investing in the technology development and the clinical data development, we've also been very focused on the operating execution of the business. What you've seen, what you would have seen from us is in the past year, we pre-announced our Q4 and our 2024 last week prior to the conference. Our unaudited top-line results were $79.4 million-$79.9 million in revenue. That's at the midpoint of that range. That's about a 22% growth rate year on year.
I'll talk a little bit more about the growth of the business, but the growth of the business has also been achieved with a strong gross margin profile as well as real good operating expense discipline in the middle part of the income statement. We've made a lot of progress on improving the burn rate associated with the business while optimizing and balancing the investments that we can see are opportunities for us when we think about the nature of the unmet need and the unique nature of the technology as well. We do that with a healthy balance sheet. We also pre-announced a cash position of $52.8 million on the balance sheet here at the end of 2024, and we feel like that cash with our cash burn provides us with flexibility through at least 2026 in the foreseeable future.
While we remain opportunistic with regard to capital markets and what we think is in the best interest to shareholders, we're not in a position of having to do anything from a balance sheet perspective and still being able to fund our key growth initiatives. That's all in the scope of where we're currently indicated. I'll spend some time talking about some significant market expansion opportunities as well. The business we've built today has really been an adult focal drug-resistant epilepsy population, and that within Level 4 comprehensive epilepsy centers. I'll talk about indication expansion as well as site of service expansion. On we go. The business that we've built today and that we're pursuing these strategies around is led by an experienced leadership team.
I'm pleased to have Rebecca Kuhn, our CFO, here in the room with me today, as well as particularly pleased to have Frank Fischer, our Chairman, here with me, as well as founding CEO as well. We bring a strong team with a lot of history as well as deep skill sets here. You see here on the slide also Dr. Martha Morrell. Dr. Morrell is a luminary in the field and is our Chief Medical Officer, as well as then Kelley Nicholas, who's newer to the team and leads our commercial organization.
We've also, in line with a number of the opportunities that we have in front of us, product launches, indication expansions, and product pipeline innovation have added some recent members to the leadership team: Brett Wingeier, a new Vice President of research and development, who's actually an alumni of NeuroPace, having returned, as well as then Katie Keller to lead our marketing and market development efforts with all of the commercial opportunities that are coming, as well as then Amy Treadwell from a human resources perspective focused on continuing to build out a world-class organization. We feel like we have world-class technology and world-class opportunities in front of us, and we're also focused on making sure we've got the world-class leadership team to go along with it. To say a bit here now and provide you some context on drug-resistant epilepsy, DRE.
Drug-resistant epilepsy is a significant unmet need within our U.S. healthcare system. It's actually the fourth most common neurologic disorder in the U.S. As you might imagine, people with drug-resistant epilepsy who are suffering from this disease have a number of impacts in their life, including things like higher unemployment rates, additional comorbidities, and high healthcare system utilization, so in addition to being able to treat the epilepsy, the downstream sequelae of untreated epilepsy are significant both for individual patients as well as for the healthcare system overall, and it's a significant fraction, so about a third of the 3.6 million epilepsy patients in the United States are drug-resistant, and so you know, 1.2 million patients out there that we're focused on in terms of closing the treatment gap. We do that with the RNS System, and I'll spend a little time talking about the system itself.
But what makes it unique is that it's a responsive neurostimulator that provides a window into the activity within the brain, both the seizure-related activity as well as then the stimulation activity that we use to attenuate the seizures themselves. What makes it unique is the closed-loop nature of the system. And so, we're constantly monitoring and then able to recognize based on the detection parameters that are set, and then being able to respond with stimulation therapy according to parameters that are programmed by the clinician, and then recording what's going on both with regard to the patient's underlying disease as well as what happens with the therapy that's administered. I should mention we record with regard to the brain activity both what we do in terms of stimulation as well as what's going on in the brain with regard to impacts from medication management and lifestyle as well.
And so, it really does provide people a window into the brain to be able to personalize and tailor therapy and allows for really a targeted, individualized therapy setting that is data-driven. We're able to use the feedback that we get to, in effect, tune the device to treat the individual patient. And we think that shows up in the clinical data, and I'll talk a little bit more about that. Here you can see the data, and there's two different data sets here on the screen. The darker blue bars in the histogram are the original FDA pivotal trial data as well as the long-term trial data that went into getting that approval. There are a couple of things that I'd like to call out here. One, as you'll see, even nine years out, a significant median seizure reduction rate, 75%.
These patients are having meaningful reductions in their seizure rates. The improvement of the data over time. In many cases, we'll actually see a deterioration of the results with technologies over time. Here we see the opposite. We see improvement. We believe that really gets back to what I was talking about earlier with some of the unique aspects of the platform that allows us to get feedback and continue to adjust and manage the patient. We know that the brain has plasticity. So, as we improve the condition, we can continue to improve the outcome. We can monitor what's going on with that patient and then further adjust detection as well as therapy delivery parameters. We see that improvement over time. The other set of light blue bars there that I'd call your attention to is our real-world study and FDA post-approval data results.
A couple of things I'd call out here. Three years in there, even better outcomes in terms of median seizure reduction at the 82% level and also improving over time. The third thing I'd call out is that we also start at a higher rate of median seizure reduction in year one. In there, I think it's really calling attention to we've learned some things over time with regard to the therapy and where to start patients, but then we continue to see our ability to tailor and target the therapy result in improved outcomes over time. We think that the unique nature of the technology is, in fact, showing up in the evidence associated with responsive neurostimulation. There are alternatives that patients have in addition to drug management. Just for clarity, the RNS System is actually indicated for adjunctive use with medicines.
It's not a device versus drug. It's a device and drug therapy that has the potential to both improve outcomes on patients with static drug regimens or allow for fewer or lower dosages of drugs to also then result in better seizure control. Here you can see there are really two alternatives to RNS therapy. One is surgery. And in a lot of ways, it was kind of the classic approach of resecting an area where there was bad actor rhythms in the brain. And for about 20% of patients, resection and/or ablation can be a real good option. One of the things that's interesting about RNS therapy is it doesn't preclude a surgical procedure. A surgical procedure cannot, by definition, be reversible.
But implanting an RNS device and being able to monitor the brain activity can help inform locations for potential resection, as well as in some cases, areas of the brain not being amenable to resection can be used in conjunction with surgery as a hybrid therapy, so surgery can be a good choice for some, but generally a specific segment and then can be used in conjunction. There are two other neuromodulation approaches: vagus nerve stimulation and deep brain stimulation. They don't offer the key aspects of the platform that I was just talking about in terms of the therapy really being able to be targeted at the seizure location, the ability to be responsive and tailored, as well as then the side effect profile. That's something I didn't talk about quite as much on the clinical data itself. We focused more on the efficacy.
But from an adverse event rate perspective, the adverse event rates that we see are very low, primarily procedurally related. And with both VNS as well as with DBS, we do see adverse events in the mid-teens for things like depressive mood, sleep disturbance, those types of things. And we think a lot of that is associated with RNS therapy being able to be tailored. You only stimulate the patient when the patient needs to be stimulated. We're constantly watching. And so, when we detect, then we stimulate. What that results in then is targeted stimulation.
With other therapies that are more of what's been commonly known as a duty cycle, where they're programmed to be on for a certain period of time and then off for a certain period of time, what you end up with is you may be stimulating during a seizure, you may not, you don't know, and then you may be stimulating more than is necessary, and as it turns out, if a patient needs their brain stimulated, you should. If they don't, you shouldn't, and with a duty cycle therapy, you end up with hours of stimulation versus with RNS therapy, you end up with minutes of targeted stimulation per day, and we think that relates to then those higher adverse event rates where you see patients who don't need the stimulation ending up responding to it, whereas with RNS, you only stimulate when needed.
So, what we're focused on really is closing the gap of patients who in that 1.2 million out there, there are about 50,000 a year that end up being referred into comprehensive epilepsy centers. And so, both within the comprehensive epilepsy center population, there's still relatively significantly low penetration of the number of surgical or neuromodulation-based procedures, as well as then a significant percentage of those patients who don't end up being referred into Level 4 centers as well. So, I'm going to spend some time now talking with you about the market and what we're doing to address that from a growth strategy perspective.
When we segment the market, the current market, the $2 billion TAM that we currently address in the Level 4 comprehensive epilepsy centers, that breaks out about 60% focal patients, meaning the seizure originates in a focused location within the brain, and about 40% of the population is generalized, meaning the seizure itself occurs kind of everywhere all at once. There isn't a focal location. We're currently indicated for the focal adult drug-resistant population, and we'll talk about our efforts there. We're also doing a significant amount of clinical work in the generalized population. The idiopathic generalized population, which is a significant segment, is the subject of our Nautilus trial, and we'll talk about the trial here in a minute, and then we're also doing work in the Lennox-Gastaut segment of patients as well.
We have recently completed a joint trial with the NIH, enrolling those patients and now moving into follow-up, so really working to expand our coverage of drug-resistant patients, and the way we're doing that is really there's three prongs to our strategy. It's pretty straightforward, and this is what we're working to execute on. One, expanding utilization and adoption within our core Level 4 comprehensive epilepsy center customers, and I'll talk more about those efforts. Two, increasing availability of the therapy, increasing access to RNS by expanding site of service delivery, and so which centers are able to implant and follow and manage RNS patients, and then three, expanding indications, so how do we expand from the adult focal population into the other meaningful segments that are available to us? These are the three legs to our strategy.
The growth that we're seeing today really comes from Level 1 of the strategy, the comprehensive epilepsy centers, and then starting to get moving on expanding access. With regard to expanding utilization in our Level 4 customers, it's really a matter of expanding patient identification and utilization. So, within the approximately 200 comprehensive epilepsy centers that exist today, you can think about five or six epileptologists within each center. So, approximately 1,200 epileptologists that can prescribe the RNS System. And within each of those centers, we may have two or three or three or four of them who are utilizing RNS therapy as a tool in their toolbox. So, a key part for us is broadening adoption within the Level 4 centers. We've continued to do that. In Q4 of 2024, we reset another all-time high in the number of active prescribers of RNS.
And so, we do continue to expand adoption of the technology. Once we've done that, then we really work on utilization. And here you can see traditionally people would think about a targeted focal lesion location to deploy RNS therapy, and some of those subsegments of patients are listed here. But then we also work to really expand how people think about patient identification and selection within their population, both to include stimulating the network versus stimulating focal locations or adjunctively to, as well as then in combination with surgery that I had talked about previously. So, as we work to expand the number of clinicians that are utilizing the device or adopting the device, rather, also working to expand utilization is a key, is really the foundation of our growth strategy and responsible for the vast majority of what we've seen here in 2024.
The second plank is expanding site of service access, and this we call Project CARE. We piloted this in 2024, and in 2025, we're planning on expanding these efforts, and this really is expanding outside of Level 4 centers, either into Level 3 centers or community centers, and what we've seen here is we started to talk about in Q3 for the first time, really started to see a meaningful impact into the business of patients both implanted in these new centers as well as then more referral coming from these centers as well, so beginning now to expand these activities through professional education as well as direct-to-consumer awareness and education efforts, but expanding access to RNS therapy through expanding site of service location is the second leg in that strategy, or second layer in that strategy, rather, and then thirdly here is indication expansion.
And I'll talk a little bit about generalized epilepsy in particular. As I mentioned, it's 40% of the market. And we've got two primary efforts in this area. One is the Nautilus trial. The trial and the indication itself do have breakthrough designation. And so, that's really a recognition from the FDA of the importance of this work. We have completed enrollment in the trial. Enrollment in the trial and implants required for enrollment in the trial was completed in Q1 of 2024. And we have a 12-month follow-up. And so, we plan for March of this year, March of 2025, to complete follow-up in these patients. And then directly following that, we'll be monitoring the data, preparing the data to lock, then writing and submitting the data to FDA as part of a PMA supplement. So, we're really excited about the work that's being done here.
It's a blinded study, so we have yet to see the data, but we're excited about what we see in terms of interest in the segment. One of the things that we note is the enrollment rate in the study. The study enrolled ahead of schedule, and so we take that as an indicator of both clinician as well as patient interest, as well as the fact that the RNS System in idiopathic generalized patients would be the first device indicated for idiopathic generalized drug-resistant epilepsy. And so, this is a big opportunity for us to bring RNS to more and more patients. Similarly, as I mentioned before, we've recently completed enrollment in our Lennox-Gastaut study, which is an early feasibility study jointly funded with the NIH, doing fundamental research and innovation in a particularly challenging patient population.
This graphic is really intended just to show the three layers in that growth strategy. One, expanding adoption and utilization within Level 4 centers. Two, expanding site of service access. When we expand site of service access, it also will help, pending a successful clinical trial, prepare us for the idiopathic generalized indication. One of the things about the focal population is that population needs to be referred to the Level 4 centers for invasive Phase II monitoring to localize the focus of the seizure. The generalized patients, since it's generalized, don't need to have that invasive Phase II monitoring to do the localization, and as a result, we won't be as limited to the Level 4 comprehensive epilepsy centers.
So, while today we build out that presence, it also helps position us and then work together strategically with when, again, pending the completion and approval of the trial and the indication, put us in position to take advantage of that untapped opportunity to serve generalized patients. And so, each of these things work independently. They also work together and allow us to leverage the position in the market as well as our investment with our key growth drivers. I did want to say a little bit about some emerging areas for us as well. One of the unique aspects of the platform that I mentioned was the ability to monitor and record data. That ability gives us a unique opportunity to provide visibility to what's going on.
We recently signed a collaboration agreement with a biotechnology company by the name of Rapport, who was actually speaking earlier this week at this conference, where we are working with them as part of a Phase II trial that they're doing to give them visibility into both patient and center selection as well as patient response upon administering of their agent, which is something we're doing all day, every day out in the market with our technology, giving physicians a window into when medication or lifestyle management changes are made, what's the impact electrophysiologically. We're doing that now here similarly as part of this trial. And it's something that Rapport was interested in investing in with us and something that we see as a potential to further leverage the value and the power of the data that is unique to the RNS System.
Another aspect of NeuroPace I'd like to give you some visibility for is a relationship that we have with a company by the name of DIXI Medical. DIXI manufactures and we distribute stereo -EEG diagnostic electrodes. Those electrodes allow us to be a participant in the diagnostic process with these patients, or if you might, kind of vertically integrate into the diagnosis process and really be aware of patients and how those patients are responding to the diagnosis that they're going through. It's a great product to give us leverage through our current salesforce and our current call point. It's also a great product to give us visibility into the patient pipeline. That's gone very well for us, and we're really pleased with that relationship. So that's our approach. We've been working this strategy to the following results. Again, 22% growth in 2024 from a revenue perspective.
You can see the quarter-on-quarter results here actually grew the business faster in the second half of the year than we did in the first half of the year. So we're pleased to see those results as well. And then just as a caveat, in 2023, we actually had the benefit of the implants from the Nautilus trial. If you back out the implants from the Nautilus trial in 2023, our 2024 growth rates are actually north of 25% from an RNS revenue perspective. So we're pleased with what we've been seeing here in the performance of the business and are looking forward to further leveraging everything that we've got going. So in summary, we feel like we're really well positioned to continue to grow the business. We feel like we've done so with good operating discipline, and that's really shown up in our effective cash management and balance sheet.
We're focused on prioritizing within our current customer population adoption and utilization expansion. Care gives us an expansion of customers, and our indication expansion opens up significant new patient population opportunities. And these opportunities are all in flight. There's a lot behind each one of these PowerPoint slides. We're executing this strategy, and we look forward to telling you more about it. One of the ways we're going to tell about it and tell folks more about it here is I will plug we have an upcoming Investor Day on January 28th in New York, where we're going to tell a little bit more of the story that we haven't told so far. We spend a lot of time and energy on clinical data development, product pipeline development, and market development-related activities.
So we intend to talk about those things as well as give our view for 2025 and beyond for the excitement we have for the strategic direction of the business. So with that, I'll stop and open it up to any questions.
Yeah. Thanks so much, Joel, for that comprehensive presentation. And I guess just to kick things off, I don't know if you want to have a seat or stand, whatever you're comfortable with. But just to kick things off, you obviously pre-announced fourth quarter. You had a good quarter. Sales were $21 million-$21.5 million. So maybe just if you want to talk a little bit about trends that you saw. I can appreciate you guys don't provide the color on centers and utilization like you did in the past, but maybe just qualitatively what you're seeing and what drove a lot of the strength in the quarter and how you're feeling about 2025?
Yeah, absolutely. We were pleased with the quarter. We were pleased with the year. And I think what we're seeing and the trends that are driving this are the things that I just spent the last 30 minutes talking to you about. It's working the strategy. So we're seeing increased adoption across prescribers within the current core customer base. We're seeing expanded utilization from the traditional focal patient population where maybe somebody has a particular sweet spot patient where they'll use RNS to broadening patient identification and utilization within those populations. And then we're now starting to see the benefit and the impact on the business from the site of service expansion work. So it's really the things that we're talking about, and it's executing the plan, and that's what's been driving the trends in the business.
I guess looking ahead then to 2025, obviously you didn't provide formal guidance today, but there are a few moving pieces, I'd say, into the year. Obviously, like you mentioned, center expansion, site of care expansion, potentially generalized contribution, as well as I believe you reached the trough of your replacement cycle in third quarter. So maybe if you could walk through the contribution or the relative contribution from each of these in 2025, what are you feeling most confident in and what should drive a lot of the strength if you had to kind of rank them?
It's a great question, and there are a number of drivers as we look forward to 2025. We've really, I think, when we see that ongoing quarter-on-quarter increase in a record number of prescribers, which was really the case throughout each quarter in 2024, I feel like we're really generating some good momentum with our commercial and field clinical organizations on expanding the footprint of prescribers. And that provides a solid foundation for us to then build out patient selection with each one of those. That's a multiplier for us. And so then as we also build out on identification and expansion of patients, we can do that off a broader base.
We've also made a fair bit of progress with the product itself in terms of ease of use and efficiency, in particular with regard to data management that affords us the opportunity to scale patient populations inside somebody's practice. We're also very cognizant of the amount of time and energy it takes to manage patients, and we're seeing the benefits from that. A couple of other things that I'd call out is we called out the Project CARE Initiative in Q3 as beginning to see meaningful impact. We continued to see that trend in Q4. We expect that a lot of the work that we were doing throughout the year then started to show up, and we intend to build on that momentum further from there.
Finally, I would point to we talked about actually last year at this conference. In our pre-announcement, we announced an incremental expansion to our salesforce and our commercial organization. As you might imagine, we have high expectations for both the type of person as well as the training of those people, and so in the first half of 2024, we hired and put those people in place and put them through training, and now in the second half of 2024, they started to kind of be released to independent activity, as it were, so given us expanded coverage and more intense coverage, both to support high-growth RNS areas today as well as the expansion of the care accounts. The expansion of the commercial organization, we expect to show increasing yield and results in 2025 as well.
I think we've got multiple shots on goal here to build momentum off of the strategy that we're starting to see yield results now and we're planning to power into.
Great. I think we just want to shift a little bit to generalized. Obviously, this is a huge opportunity, potentially doubles your TAM, though it's also an area where you could face a little bit more competition from VNS and DBS as those therapies are a bit more kind of effective in this population. I can appreciate also you provided a lot of fantastic longitudinal data for RNS currently in the focal patients over the years. That's obviously probably contributing to the value proposition as you kind of move or continue expanding in focal.
But as you look at generalized, how do you plan or what's your strategy to kind of overcome that initial kind of physician or surgeon hesitation in the beginning, given you'll only have kind of that one data set that you can show? And I guess what gives you confidence that the product, obviously pending the data, is going to be formidable versus some of the competitor devices and therapies?
It's a really good question. I might take the opportunity to rebut a little bit with regard to competitive dynamics there. Nobody else has developed the data, and that's what we're doing. And so we think we're going to put ourselves in a very strong competitive position, again, pending successful completion of the trial, which we don't know. It's a blinded trial.
But we feel like we're doing the work to establish the evidence set to demonstrate the unique aspects of RNS as a technology. And nobody else has done that. So we intend to lead with, just as we always have, and you mentioned, lead with the data, lead with the science, and how the two work together. I feel that additionally, we're in a particularly strong position here given that the fundamental precepts of the RNS system, the ability to monitor, sense, detect, treat, record, while we're doing the research to find out what that'll show us, the foundation principles are the same and puts us in a position to be able to, again, tailor and target treatment for a population today that the answer is when we don't have medicines that are going to work.
The drug-resistant epilepsy, in particular, we're focused on the idiopathic generalized population in this study. The answer for those patients today is there isn't anything else we can do for you. We don't have any other indicated technologies. VNS isn't indicated. DBS isn't indicated. As far as we know, nobody's doing the studies. We are. And so we feel like as leaders in the field, this is important for us to do. It's going to put us in a strong position to differentiate the technology as well as to make the point that we are doing the work. And in the end, we feel like the combination there of the technology and the data will put us in a strong position to be able to do so.
Great. I guess just to close things off, last question here, maybe just about your spend priorities in 2025 as well as potentially your use of cash and your cash position. How is the progression of your cash burn moving forward? What does that look like? And also, could you just share some of the investment priorities that you have in 2025?
You bet. So as part of our pre-announcement, we announced that we ended the year with $52.8 million in cash on the balance sheet, as I think I had mentioned. We've been burning in the high teens. And again, we really feel like our triple aim here has been to optimize investment to grow the top line, maintain strength of performance and gross margin, and then demonstrate discipline from a variable spending perspective in the middle part of the income statement. I think you've seen that.
We're not going to hesitate to invest in the business to take advantage of the growth opportunities that we see that are in front of us. We think they're real and they're world-class, and we're going to make sure that we invest in them. But you're also going to see a disciplined and responsible approach here. We take a grow as we go approach to it, and we intend to maintain that discipline, but again, aren't going to hesitate to invest in the business. Our focus and priorities really are the three parts of the strategy that you've seen here, continuing to execute on expanding adoption and utilization and everything that goes along with that organizationally and program-wise, launching Project CARE 2.0 to expand our site of service delivery, and then executing on the clinical studies that we have underway. I've talked about Nautilus.
I haven't talked about, so maybe some of you have to tune in for the Investor Day, but I haven't talked about we've recently submitted our post-approval study to the FDA, and we plan to talk more about that data, but it'll be the largest prospectively enrolled post-approval study monitored by the FDA in history, and we're looking forward to talking more about that data, as well as talking more about the work that we're doing in pediatrics, and so execution with comprehensive epilepsy center customers to expand utilization and adoption, execution with regard to Project CARE 2.0, and execution with regard to the clinical data development, as well as our product development pipeline or our areas of focus.
Lots of exciting updates. Well, thank you so much and look forward to the Investor Day. Thanks, everyone.
Thank you, Rohin.